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High pressure and anesthesia: compressibility, molal volume, and partial molal volume of volatile anesthetics. This study was undertaken to provide volume data of volatile anesthetics under high pressure. Molal volumes of liquid halothane, enflurane, and isoflurane and their partial molal volumes in water and in 1-octanol were determined by high-precision solution densitometry at 25.000 +/- 0.0005 degrees C over the pressure range from ambient to 34.56 MPa (341 atm). The isothermal compressibilities of the pure anesthetics and their isothermal partial molal compressibilities at their infinite dilution in water and in 1-octanol have also been calculated at 0.1013 MPa (1 atm). | Mid | [
0.6340326340326341,
34,
19.625
] |
Introduction {#s1} ============ The causal agent of Chagas disease, *Trypanosoma cruzi*, is an obligate intracellular parasite of the kinetoplastid family that infects upwards of 7 million people in the Americas with \~30% developing life-threatening clinical disease (WHO, [@B88]; Perez-Molina and Molina, [@B66]). Like many trypanosomatids that cause disease in humans, *T. cruzi* is characterized by having a dixenous (two-host) life cycle that alternates between the hematophagous triatomine insect vector and its endothermic vertebrate reservoir that includes humans. Although the acute stage of infection is generally controlled by a highly effective immune response, total clearance does not occur, resulting in a life-long and often debilitating chronic infection (Groom et al., [@B35]). We currently lack the basic tools to effectively combat this pathogen, as methods of diagnosis are unreliable and drug treatments (Nifurtimox and Benznidazole) are both highly toxic and unable to eliminate the infection entirely (Camandaroba et al., [@B12]; Mejia et al., [@B58]; Molina-Garza et al., [@B60]; Maguire, [@B50]; Kansiime et al., [@B40]). As with any attempt to control an infectious disease, a better understanding of *T. cruzi\'s* basic biology is necessary for the effective identification of the areas where these parasites are most susceptible to therapeutic intervention (Alvarez et al., [@B5]). One of the most poorly understood aspects of *T. cruzi* biology centers around the question of how this parasite exploits host resources in order to proliferate. Some important clues, however, have come from phylogenetic analyses tracing the evolution of kinetoplastids and their transition from bacterivorous predators to obligatory parasites. Although the most heavily studied kinetoplastids are the disease causing parasites of humans and domesticated animals (*Trypanosoma* spp. and *Leishmania* spp.), these organisms originally evolved from environmentally ubiquitous free-living, flagellated protozoans of the Excavata supergroup (phylum Euglenozoa) (Simpson et al., [@B73]; Lukes et al., [@B47]). These early branching eukaryotes comprise a diverse family of flagellates characterized primarily by the presence of an "excavated" feeding groove used to funnel food into the mouth of the cell, a plasma membrane pore known as the cytostome. This pore is continuous with a single tubular invagination (cytopharynx) adjacent to the flagellar pocket that extends to the posterior end of the cell. Extracellular material captured via this feeding apparatus \[referred to collectively here as the cyto[s]{.ul}tome-cyto[p]{.ul}harynx [c]{.ul}omplex (SPC)\] is subsequently endocytosed and targeted for lysosomal degradation (Eger and Soares, [@B26]). The extant free-living relatives of trypanosomatids, broadly classified as bodonids (e.g., *Bodo saltans*), can be found in virtually any marine or freshwater habitat where they primarily filter feed using the SPC endocytic pathway to phagocytose their bacterial prey. It has therefore been assumed that SPC mediated phagotrophy of prokaryotes was, most likely, the ancestral mode of nutrient acquisition in the first kinetoplastids (Stevens, [@B81]; Flegontova et al., [@B30]). With the recent identification of the earliest branching monoxenous trypanosomatid, *Paratrypanosoma confusum*, as the "missing link" between *B. saltans* and the dixenous trypanosomatids (Simpson et al., [@B73]; Stevens, [@B80]), it has become clear that obligatory parasitism first began as an association with the arthropod lineage (propagated via fecal/oral transmission) and that the dixenous parasitism we see in the pathogenic trypanosomatids likely arose independently on several occasions. It is notable that the dixenous stercorarian trypanosomes (which includes *T. cruzi*) still rely on fecal transmission from the insect to their vertebrate host. This initial transition of free-living kinetoplastids into arthropod parasites coincided with an acute reduction in the size of their genome (\~50% gene loss), which included the loss of many metabolic pathways (Opperdoes et al., [@B63]). This streamlining was also accompanied by the abandonment of their second flagellum (Deschamps et al., [@B25]; Harmer et al., [@B36]). Despite all these changes however, the SPC structure of monoxenous trypanosomatids has remained intact, suggesting a continued role in nutrient uptake suited for life in the insect gut. Curiously, in the second major transition of the pathogenic trypanosomatids to a dixenous lifestyle, *T. cruzi* alone retained the SPC whereas the salivarian lineages (*Trypanosoma brucei* and *Leishmania* spp.) abandoned this endocytic structure entirely (Porto-Carreiro et al., [@B67]; Field and Carrington, [@B28]). Although we do not know definitively why *T. cruzi* has retained the SPC, there is clearly an interesting correlation between the distinct replicative niches inhabited by a parasite and its mode of nutrient uptake. *T. brucei*, for example, divides extracellularly in the bloodstream of mammals where the host provides simple amino acids and sugars at high levels that can be readily transported across its plasma membrane to facilitate growth (Mazet et al., [@B57]; Creek et al., [@B19]; Mathieu et al., [@B56]; Marchese et al., [@B51]). Apparently, only host iron sequestering proteins, such as transferrin, still need to be brought into the parasite cell directly via receptor-mediated endocytosis at the flagellar pocket (Coppens et al., [@B17]; Schell et al., [@B71]; Mach et al., [@B48]). *Leishmania* spp. on the other hand, do replicate within host cells, but rather than live freely in the cytoplasm, they reside within lysosome-like vacuoles of specialized phagocytic cells. As a result, *Leishmania* spp. occupy a low pH environment replete with proteases that actively digest host macromolecules into a milieu of simple nutrients (Alexander, [@B4]; Antoine et al., [@B7]; Russell et al., [@B70]). *T. cruzi* is therefore the only trypanosomatid that lives directly in the host cytoplasm and is one of the few protozoan parasites that inhabit the cytosol of nucleated cells, making this replicative niche a surprisingly rare choice (de Souza et al., [@B22]; Barrias et al., [@B8]). One possible reason for this rarity comes from recent work demonstrating that the cytosolic environment of host cells is far less conducive to pathogen growth than previously thought (Goetz et al., [@B33]). The cytosol, despite having abundant macromolecules, is deficient in freely available amino acids, when compared to the mammalian bloodstream or host cell lysosomes (O\'Riordan and Portnoy, [@B64]; Abu Kwaik and Bumann, [@B1]). *T. cruzi* may have retained the SPC, in part, as a mechanism for amastigotes to harvest host cytoplasmic macromolecules as the fuel required for rapid parasite growth. Direct digestion of these materials via the SPC complex would provide *T. cruzi* with metabolites that are otherwise scarce in the host cytoplasm. This seemingly "non-specific" method of nutrient uptake could also explain how *T. cruzi* is able to grow and propagate in such a wide variety of hosts and cell types (Browne et al., [@B11]). Alternatively, the loss of the SPC in *T. brucei* or *Leishmania* sp. may be due to the fact that these organisms undergo critical developmental changes in the mid and foregut of their arthropod vectors whereas *T. cruzi* alone develops into its infectious stage in the hindgut as part of its stercorarian transmission lifestyle (reviewed in Goncalves et al., [@B34]). The SPC may therefore serve a critical role for trypanosomatids needing to successfully navigate the insect hindgut. It appears as though the fecal/oral transmission route for the monoxenous trypanosomatids like *P. confusum* is the ancestral form of transmission still retained by *T. cruzi* albeit as part of its vertebrate transmission strategy (Flegontov et al., [@B29]). Our current understanding of the complex organization and dynamics of the SPC in *T. cruzi* is derived primarily from a combination of extensive electron microscopy studies including scanning, transmission and tomography based 3D reconstructions (Steinert and Novikoff, [@B79]; Milder and Deane, [@B59]; Preston, [@B68]; Martinez-Palomo et al., [@B55]; De Souza et al., [@B23],[@B24]; Souto-Padron and de Souza, [@B76]; Okuda et al., [@B62]; Vatarunakamura et al., [@B85]; Correa et al., [@B18]; Souza, [@B77]; Alcantara et al., [@B2]). First, the membrane tubule itself is embedded between two distinct sets of microtubule root fibers; one set of triplet microtubules initiating at the cytostome entrance and a second quartet of microtubules beginning at the centrosome near the base of the flagellar pocket, abutting the plasma membrane to form an intriguing surface prominence known as the pre-oral ridge (POR) before descending again into the cytosol and serving as a guide for the construction of the cell spanning SPC structure (Alcantara et al., [@B2]). In addition to its structural complexity, the SPC is also highly dynamic, as it disassembles in the infectious/non-dividing forms (metacyclics and trypomastigotes) and reconstitutes itself in the replicative stages (epimastigotes and amastigotes) (Vidal et al., [@B86]). It is also thought to break down during cytokinesis (Alcantara et al., [@B3]). Although the cytostome membrane pore and tubular invagination are lost during disassembly, the underlying microtubule structures appear more stable, potentially allowing for the rapid regeneration of this organelle (Alcantara et al., [@B2]). The ultimate result of these changes is that endocytosis ceases in the metacyclic and trypomastigote forms, only to become measurable again after stage conversion and cell division resumes (Vidal et al., [@B86]). Why the SPC disassembles in these non-replicative stages of *T. cruzi* has never been determined, but it may function as a defense against bringing in host antimicrobial proteins or more simply because the infectious forms are no longer replicating and have no need to consume additional complex metabolites. Despite the detailed structural analysis of the SPC, there is still a great deal that remains unknown about this primordial feeding apparatus including the identity of proteins responsible for its construction, function and capture of endocytosed cargo. We report here the identification of the first known proteins specifically targeted to the enigmatic cytostome-cytopharynx complex in *T. cruzi*. Our initially identified SPC targeted protein (CP1), was endogenously Ty-epitope tagged and shown to localize with several fluorescently labeled cargo proteins, consistent with its targeting to the endocytic organelle. As expected, the CP1 localization to the SPC was dynamically regulated and disassembled in the infectious trypomastigote and reestablished in the replicative stages. Overexpressed CP1-mNeon-Ty underwent normal trafficking and thus facilitated visualization of the SPC for the first time in live parasites. When characterizing the localization of CP1, we observed that co-staining of the parasite surface with the mannose binding lectin Concanavalin A (ConA) allowed us to determine, using super-resolution light microscopy alone, the region of the SPC entrance and pre-oral ridge, which we suspect plays an instrumental role in the binding efficiency of nutrient endocytosis. Finally, our immunoprecipitation (IP) of CP1, followed by mass spectrometry (MS) analysis led to the identification of two additional SPC associated proteins (CP2 and CP3), which also label the protein endocytic pathway, thus validating their interaction with CP1. This work reveals a first glimpse into the proteome of the SPC and provides the necessary tools for further characterization of this unusual endocytic organelle. Materials and Methods {#s2} ===================== Parasite Cultures ----------------- Epimastigotes of *T. cruzi* Y strain were cultured in LDNT/LIT medium (Kirchhoff et al., [@B42]) supplemented with 15% FBS. Aliquots of FBS (VWR, USDA certified) were freshly heat inactivated at 76°C for 40 min (to help improve epimastigote viability at low numbers) prior to addition to the media (this heat inactivated FBS will precipitate if frozen). To obtain amastigotes, 1 mL of maximum density epimastigotes were differentiated to metacyclic trypomastigotes via prolonged starvation in depleted LIT media (for at least 3 days). The resulting parasites were then incubated overnight with fresh FBS (with intact complement) to kill any remaining epimastigotes. The surviving metacyclic trypomastigotes were added to flasks containing human foreskin fibroblasts (HFF) grown in High Glucose Dulbecco\'s Modified Eagle\'s Medium (DMEM-HG) (Hyclone) supplemented with L-glutamine and 10% heat-inactivated (56°C) Cosmic Calf serum (CCS) (Hyclone). After 24--48 h media was replaced with medium containing only 1% (CCS) for further culturing. Generation of Cloning Constructs and Transfection ------------------------------------------------- C-terminal tagging of CP1 was performed as described by Lander et al. ([@B44]), the Ty epitope sequence, fused to a downstream hygromycin selection cassette, were first amplified with 40bp homology arms for insertion upstream of the CP1 stop codon (P1 and P2). This product was co-transfected with the SpCas9 vector generated by Lander et al. modified to contain a gRNA protospacer (P6) targeted to a site between the two chosen 40 bp homology regions. Mutants were selected with both Hygromycin (250 μg/mL) (Fisher Scientific) and G418 (400 μg/mL) (Corning). For overexpression of mNeon-Ty tagged proteins, we utilized the pTREX vector (Martinez-Calvillo et al., [@B54]) modified with a *T. cruzi* optimized and "fixed" Neomycin resistance cassette (IDT Geneblock) (see **Figure 3A**) that allowed us to stringently select with 2,000 μg/mL G418. We also modified the vector to contain a *T. cruzi* optimized mNeon-Ty sequence (Shaner et al., [@B72]) (IDT Geneblock). Final vector products were generated and assembled using standard Gibson assembly parameters (Gibson et al., [@B32]) and primers (CP1: P7,P8 CP2: P9,P10 CP3: P11,P12) using the NEB HiFi Assembly kit. P6 and P7 primers were utilized to amplify the vector for Gibson assembly. Parasites were transfected as described by Lander et al. ([@B45]) using a BTX ECM830 (Harvard Apparatus). Primers used for cloning are identified in [Supplementary Table 1](#SM7){ref-type="supplementary-material"}. Western Blot Analysis and Immunofluorescence Assays --------------------------------------------------- For Western blot lysates, 1 × 10^7^ epimastigotes were spun down at 1,200 × g then washed 1x in PBS. Pellets were then resuspended in 1x SDS PAGE sample buffer (LICOR) containing β-mercaptoethanol. Half of the sample (5 × 10^6^ epimastigote equivalent) was loaded into each well and Western blotting was performed via the general established protocol. Western blotting antibody dilutions: 1:500 for α-CP1 mouse and 1:1,500 for α-Ty mouse (mAb BB2) (Gay et al., [@B31]) LICOR 800 α-mouse was used as secondary antibody at 1:20,000 and images were taken in a BioRad Chemidoc. Total protein loading controls were imaged from stain-free TGX gels prior to membrane transfer. Immunofluorescence assays (IFA) were performed as previously described (Chasen et al., [@B13]) with modifications for epimastigotes. Epimastigote were washed in nutrient free pH 7.2 Triatomine Artificial Urine media (nfTAU) (Chiurillo et al., [@B15]) prior to fixation in nfTAU containing 3.5% paraformaldehyde (Electron Microscopy Sciences). Cold fixation solution was added to parasites and allowed to fix and equilibrate to room temperature for 20--30 min. Fixed parasites were allowed to adhere in nfTAU to poly-l-lysine coated cover slips for 30 min prior to proceeding with the IFA protocol. IFA antibody dilutions: 1:500 for α-CP1 mouse and 1:1,100 for α-Ty mouse monoclonal. α-mouse Alexafluor-488 and Alexafluor-568 antibodies were used as secondary antibodies. Coverslips were mounted to slides using Prolong Antifade mounting media (Invitrogen). Endocytosis Assays ------------------ For fluorescent epimastigote endocytosis assays, 1 × 10^7^ epimastigotes were chilled on ice and then spun down in a 4°C centrifuge at 1,200 g. Parasites were then resuspended in 500 μl of chilled complete TAU (pH 7.2) containing 25 μg/mL BSA-Rhodamine (Rockland Immunochemicals), 25 μg/mL Transferrin-488 (Molecular Probes), and 10 μg/mL α-Rabbit Alexafluor-568 IgG (Thermo Fisher) and then incubated at 28°C for 25 min. Parasites were then spun down at 4°C and the supernatant removed prior to resuspension of the pellet in 1.5 mL of 4°C nfTAU containing 4% paraformaldehyde (Electron Microscopy Sciences). Fixation was allowed to progress at room temperature for 30 min before spinning down for slide mounting and fluorescence imaging as described above. For intracellular amastigote endocytosis assays, coverslips with HFF monolayers were treated with CellTrace CFSE as described in the commercial protocol (Invitrogen). After labeling, cells were washed three times and followed by a 3 h recovery in 10% FBS containing DMEM-HG. CP1-Ty trypomastigotes were then added to the culture and 48 hrs later amastigotes were lysed out of the cells using a 16-gauge needle. Amastigotes were fixed and attached to coverslips as described above for epimastigotes. Otherwise, IFA\'s were performed as described above using α-Ty primary antibody (mAb BB2) and Alexafluor-568 secondary (Thermo Fisher). For cytochalasin B experiments, epimastigotes were pre-treated for 10 min at 28°C with cytochalasin B (300 μM, Enzo Lifesciences) prior to performing the endocytosis assay. Cytochalasin B concentration was maintained during entirety of the assay. Concanavalin a Labeling of mNeon Overexpression Mutants ------------------------------------------------------- Prior to fixation, 1 × 10^7^ epimastigotes of the mNeon overexpression lines were chilled, spun at 1,200 g, and washed 1x ice-cold nfTAU (pH 7.2). They were then incubated on ice in TAU (pH 7.2) containing 10 μg/mL Rhodamine Conjugated Concanavalin A (ConA) (Vector Laboratories). After spinning down in a pre-chilled 4°C centrifuge, the supernatant was removed, and the pellet was immediately resuspended in 1.5 mL of cold fixative (4% paraformaldehyde in nfTAU pH 7.2) and allowed to equilibrate to room temperature for 30 min, fixed parasites were resuspended in nfTAU prior to adhering to coverslips as described above. Fluorescent Microscopy ---------------------- IFA and routine fluorescence images were taken using the Zeiss Elyra S1 Structured Illumination Microscope in the Center for Tropical and Emerging Diseases microscopy core. Immunoelectron Microscopy ------------------------- CP1-Ty epimastigotes were washed twice with PBS before fixation in 4% paraformaldehyde (Electron Microscopy Sciences, PA) in 0.25 M HEPES (pH 7.4) for 1 h at room temperature and then in 8% paraformaldehyde in the same buffer overnight at 4°C. Parasites were pelleted in 10% fish skin gelatin, and the gelatin-embedded pellets were infiltrated overnight with 2.3 M sucrose at 4°C and frozen in liquid nitrogen. Ultrathin cryosections were incubated in PBS and 1% fish skin gelatin containing mouse α-Ty antibody at a 1/100 dilution and then exposed to the secondary antibody that was revealed with 10-nm protein A-gold conjugates. Sections were observed and images were recorded with a Philips CM120 electron microscope (Eindhoven, the Netherlands) under 80 kV. Analysis of Sequence, Alignment, Tree Generation, and Structure Prediction -------------------------------------------------------------------------- Alignments were generated using T-Coffee (Madeira et al., [@B49]) and figures were generated using Jalview 2 software (Waterhouse et al., [@B87]). Tree was generated in Geneious Prime using the Jukes-Cantor and neighbor-joining parameters with the *B. saltans* CP2 related sequence as an outgroup. Consensus tree was generated using a random seed and 100 bootstrapped replicates with a support threshold of 90%. Structure predictions were generated using the I-TASSER server (Yang and Zhang, [@B90]). Purification of Recombinant Antigen and Mouse Polyclonal Antibody Generation ---------------------------------------------------------------------------- The chosen antigenic region of CP1 (CP1Ag) was identified using the IEDB suite of antigenicity prediction software (<http://tools.immuneepitope.org/bcell/>) (Chou and Fasman, [@B16]; Emini et al., [@B27]; Karplus and Schulz, [@B41]; Parker et al., [@B65]; Kolaskar and Tongaonkar, [@B43]; Bogitsh et al., [@B10]; Larsen et al., [@B46]; Jespersen et al., [@B38]). The DNA sequence for CP1Ag was amplified from *T. cruzi* genomic DNA and cloned into the pET-32 LIC/EK vector (Novagen), which adds an N-terminal thioredoxin and histidine tag to the expressed protein. Recombinant CP1Ag was expressed and initially purified via a nickel-affinity column (HisPur Thermo Fisher) as previously described (Chasen et al., [@B13]). This initial purified fraction was digested using biotinylated thrombin to cleave the N-terminal thioredoxin-tag and histidine tag. After thrombin removal, the antigen was again passed through the nickel column and the purified tag-less antigen was gently eluted using 10 mM imidazole, leaving the tag attached to the column. Antibodies in mice were generated as previously described (Chasen et al., [@B14]). Swiss Webster mice (Charles River) were inoculated intraperitoneally with 100 μg of Cp1Ag mixed with complete Freund\'s adjuvant, followed by two boosts with 50 μg of CP1-Ag, with each boost being mixed with incomplete Freund\'s adjuvant. The final serum was collected by cardiac puncture after CO~2~ euthanasia. The animal protocol used was approved by the UGA Institutional Animal Care and Use Committee (IACUC). Co-immunoprecipitation and Mass-Spectrometry {#s3} ============================================ For each immunoprecipitation, a 50 mL culture of epimastigotes was grown to mid-log phase (1-2x10^7^ epimastigotes/mL) and a co-immunoprecipitation using the Ty peptide for elution was performed as described by Huet et al. ([@B37]). For identification of excised bands, matrix assisted laser desorption ionization (MALDI) was performed using a Bruker Autoflex (TOF) mass spectrometer. Shotgun mass spectrometry of eluates was performed on an Orbitrap Elite system with ESI ion source and an interchangeable nanospray source. Epimastigote Growth Assays {#s4} ========================== 2.5 × 10^6^ epimastigotes of each strain were resuspended in LIT containing 15% heat inactivated FBS. Counting was performed every 24 h using a Coulter Counter (Beckman Coulter). Growth assays were performed in triplicate and fold-change significance was determined via unpaired *t*-tests using the Prism Software Suite. Results {#s5} ======= Identification of the First Cytostomal Protein (CP1) Specifically Targeted to the Cytostome-Cytopharynx Endocytic Organelle --------------------------------------------------------------------------------------------------------------------------- As part of an ongoing epitope tagging and localization screen being conducted in the Y-strain of *T. cruzi*, we utilized a CRISPR/Cas9 mediated endogenous tagging strategy as described by Lander et al. whereby the Cas9 nuclease, in combination with a gRNA targeting the 3′ end of the hypothetical protein (TriTrypDB: TcCLB.506789.150, NCBI Accession: [XP_819915.1](XP_819915.1)) ([Figure 1A](#F1){ref-type="fig"}) was transfected into parasites. This was followed by dual selection of both a repair template containing the introduction of a C-terminal Ty-epitope (Hygromycin) and the gRNA/Cas9 expression vector (G418) ([Figure 1B](#F1){ref-type="fig"}). A diagnostic PCR to assess the loci specific modifications to the genomic DNA demonstrated a product of the predicted size for the epitope tagged locus only in the tagged strain with no products being observed for the parental locus, confirming the successful tagging of both genomic loci ([Figure 1C](#F1){ref-type="fig"}). The annotated open reading frame (ORF) of this gene, which we have renamed CP1, encodes for an 841 amino acid (aa) protein, with a predicted isoelectric point of 5.57 and a predicted molecular weight of 93.0 kDa. Although annotated as a hypothetical protein, CP1 does contain a predicted structural maintenance of chromosome (SMC) domain (TIGR02168, 455-670 aa) ([Figure 1A](#F1){ref-type="fig"}) most likely due to the presence of a potential coiled coil structure. This protein lacks any orthologs outside the closely related *Trypanosoma theileri, Trypomanosoma rangeli*, and *Trypanosoma grayii*. A western blot of CP1-Ty epimastigote lysate showed CP1-Ty to migrate at a size of \~80 kDa ([Figure 1I](#F1){ref-type="fig"}), which is below the predicted molecular weight of 93 kDa, potentially indicating N-terminal processing or post-translation modification of CP1-Ty. In images from immunofluorescence assays (IFA) taken using super-resolution structured illumination microscopy (SR-SIM), we noted the localization of CP1-Ty to a distinct linear structure that was present in both of the replicating stages, the epimastigote and amastigote ([Figures 1D,F](#F1){ref-type="fig"}), but was absent in the non-replicating trypomastigote stage ([Figure 1E](#F1){ref-type="fig"}). This structure, and its stage-specific nature, were reminiscent of the endocytic organelle of *T. cruzi*, referred to here as the cyto[s]{.ul}tome/cyto[p]{.ul}harynx [c]{.ul}omplex (SPC) (summarized in [Figure 1G](#F1){ref-type="fig"}). Cryogenic immuno-electron microscopy (CryoIEM) analysis of CP1-Ty also showed its localization to convoluted, multibranched tubular structures in proximity to the flagellar pocket (FP) and kinetoplast (K) ([Figure 1H](#F1){ref-type="fig"}). {ref-type="supplementary-material"}). An amino acid scale is below the schematic. **(B)** Cartoon showing CRISPR Cas9 C-terminal tagging strategy used to tag CP1. A guide RNA with a protospacer targeted to the CP1 3′ UTR near the ORF directs spCas9 to form a double stranded break **(B**ii**)**. A Ty-tagging repair template containing 40 bp homology, for both the 3′ end of the CP1 ORF and the 3′ side of the cut-site **(B**i**)**, was co-transfected to endogenously tag the CP1 locus **(B**iii**)**. **(C)** PCR of genomic DNA from CP1-Ty mutants confirms the C-terminal tagging of both endogenous CP1 loci. **(D--F)** SR-SIM IFA showing the linear structure labeled by CP1-Ty in an epimastigote **(D)** and amastigote **(F)**. In **(E)**, a trypomastigote lacking the CP1-Ty labeled structure is shown. **(G)** Cartoon showing the structure and breakdown of the SPC in the different *T*. cruzi life cycle stages. **(H)** Cryogenic immunoelectron microscopy of an epimastigote showing immuno-gold labeling of CP1-Ty at the cytostome (CS). Gold particles are 10 nm. **(I)** αTy immunoblot of lysates from Parental, CP1-Ty, and CP1-mNeon-Ty overexpression mutants shows a faint band of CP1-Ty (blue arrow) and a strong band of overexpressed CP1-mNeon-Ty (green arrow) Scale bars: IFA 2 μm, EM 100 nM.](fcimb-09-00445-g0001){#F1} CP1 Labels the Protein Endocytic Pathway of the Cytostome-Cytopharynx Complex ----------------------------------------------------------------------------- As previous work in the field supported the role of the SPC as the primary route of protein endocytosis in *T. cruzi* epimastigotes, we performed endocytosis assays to confirm that the CP1 labeled structure was targeting to this endocytic organelle. We fed epimastigotes fluorescent Transferrin ([Figure 2A](#F2){ref-type="fig"}), goat Immunoglobin (IgG) ([Figure 2B](#F2){ref-type="fig"}), and Bovine Serum Albumin (BSA) ([Figure 2C](#F2){ref-type="fig"}) to label the endocytic pathway and observed, through co-staining, that CP1-Ty labeled the endocytic pathway of the SPC for all three proteins. The SPC is remarkable in its apparent lack of specificity for cargo as it appears capable of endocytosing any protein we provide. It is notable that we only observed endocytosis via the SPC and failed to detect protein uptake through the flagellar pocket. This is in stark contrast to *T. brucei* which endocytoses exclusively through its flagellar pocket and to previously published reports of *T. cruzi* (de Figueiredo and Soares, [@B20]; Kalb et al., [@B39]). In order to evaluate endocytosis in intracellular amastigotes, we stained host cells first with the free-amine labeling fluorescent dye CFSE followed by infection with trypomastigotes from the CP1-Ty tagged line. After conversion to replicative amastigotes and growth for 48 h, amastigotes were released mechanically, fixed and stained with α-Ty antibodies (summarized in [Figure 2D](#F2){ref-type="fig"}). We observed that endocytosed CFSE labeled host-cell protein colocalized with the CP1-Ty labeled structure in amastigotes, further confirming that this structure was the endocytic organelle ([Figure 2E](#F2){ref-type="fig"}). These images also showed, for the first time, that amastigotes endocytose human host-cell cytosolic protein via the SPC. {#F2} Fluorescently Tagged and Overexpressed CP1 Traffics to the Cytostome-Cytopharynx Complex ---------------------------------------------------------------------------------------- When cloning the CP1-mNeon-Ty overexpression constructs ([Figure 3A](#F3){ref-type="fig"}) we sequenced the drug marker of the pTREX vector and observed a G → T point mutation in the conserved catalytic region of the neomycin phosphate transferase II protein (NPTII). This mutation results in a substitution of an aspartic acid for the glutamic acid at position 182 and is known to dramatically reduce the resistance conferred by NPTII (Yenofsky et al., [@B91]). It had been suggested in this prior report that this less active form of the neomycin drug resistance marker may have been inadvertently propagated throughout numerous constructs in multiple research communities. We hypothesized that this mutation may be the cause for the lackluster G418 resistance conferred to epimastigotes (200--400 μg/mL) (Torres-Silva et al., [@B82]), which results in slow killing of wild type parasites lacking the cassette as well as potentially forcing the massive duplication and ultimately exaggerated overexpression by this vector in the resulting stable transfectants. To decrease the time of selection after transfection, we replaced the NPTII coding region with a *T. cruzi* codon-optimized version lacking the E182D substitution and increased drug selection pressure ([Figure 3A](#F3){ref-type="fig"}, inset). This "fixed" version of NPTII allowed selection of our CP1-mNeon-Ty overexpressing epimastigotes with higher drug selection conditions up to 2,000 μg/mL of G418. Western blot analysis of lysate from this mutant population showed a strong band around the predicted molecular weight of 132 kDa ([Figure 1I](#F1){ref-type="fig"}). SR-SIM microscopy revealed that the fusion protein of CP1-mNeon-Ty trafficked normally in epimastigotes as it colocalized with endocytosed BSA-Rhodamine along the length of the endocytic pathway ([Figure 3B](#F3){ref-type="fig"}) When these mutants were pre-treated with Cytochalasin B, we observed that endocytosis was prevented ([Figure 3C](#F3){ref-type="fig"}) as has previously been described (Bogitsh et al., [@B10]). As observed in this endocytosis blocking experiment (+Cyt), BSA clearly binds strongly to a region adjacent to the SPC entrance, also known as the pre-oral ridge (POR), which lies between the entrance of the flagellar pocket and the cytostome. The binding of a number of proteins at the POR prior to being endocytosed has been observed previously in primarily EM experiments (Vidal et al., [@B86]). It was also observed in our localization experiments, that in the absence of a permeabilization step, the endocytosed cargo displayed a markedly packet-like appearance ([Figure 3B](#F3){ref-type="fig"}, see BSA-Rhodamine) as opposed to the continuous linear presentation of cargo observed when cells are permeabilized (see [Figure 2A](#F2){ref-type="fig"}). When amastigotes expressing CP1-mNeon-Ty were imaged within host cells, the same tubular pattern reminiscent of the SPC was again observed ([Figure 3D](#F3){ref-type="fig"}). By combining the CP1-mNeon-Ty expressing parasites with Concanavalin A (ConA) staining at 4°C, followed by fixation, we observed a unique labeling of two linear structures emerging from the flagellar pocket with one following the parasite body along the flagellar attachment zone and the other stopping abruptly at the POR and SPC entrance. This staining pattern seemed to confirm for the first time using light microscopy, what had been seen in prior reports using EM techniques, that the POR contains a concentration of mannose containing glycans ([Figure 3E](#F3){ref-type="fig"} arrow) (Martinez-Palomo et al., [@B55]). The CP1-mNeon-Ty overexpressing parasites also allowed us to validate previous findings that parasites undergoing division ([Supplementary Figure 1A](#SM1){ref-type="supplementary-material"}) and infectious trypomastigotes ([Supplementary Figure 1B](#SM1){ref-type="supplementary-material"}) lack defined SPC structures (Alcantara et al., [@B3]). {#F3} Identification of Two Additional Cytostome-Cytopharynx Proteins Associated With CP1 ----------------------------------------------------------------------------------- Taking advantage of our identification of CP1, we performed an immunoprecipitation to identify other SPC proteins for the continued characterization of this organelle and its structural components. We generated soluble lysate under native preserving conditions from our CP1-mNeon-Ty overexpressing parasite line and performed a pulldown using α-Ty antibody conjugated to paramagnetic beads with protein complexes being eluted through the use of excess Ty peptide. Eluates were run on an SDS-PAGE gel and proteins were visualized using BioRad Oriole Total Protein Stain. Individual band analysis combined with MALDI based-mass spectrometry demonstrated that the uppermost band was CP1-mNeon-Ty, confirming a successful pulldown ([Figure 4A](#F4){ref-type="fig"}). Whole complex liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed two additional proteins of interest that were both absent from the control and with a notable lack of orthologs in the SPC-less *T. brucei* and *Leishmania* spp. ([Figure 4B](#F4){ref-type="fig"}). {#F4} The first target to be characterized, CP2 (TcCLB.506301.60 NCBI Accession: [XP_807919.1](XP_807919.1)), is a hypothetical protein that, like CP1 is found only in the closely related *Trypanosoma* species, as well as within the earliest branching trypanosomatid *P. confusum*, which retains the SPC (Skalicky et al., [@B74]). This protein is 720 aa long with a predicted molecular weight of 80 kDa and isoelectric point of 5.02. CP2, like CP1, also contains a predicted SMC domain (TIGR02168, 35-307 aa) ([Supplementary Figure 2A](#SM2){ref-type="supplementary-material"}). The C-terminal region of CP2 is also highly conserved amongst all predicted orthologs (675--720 aa) ([Supplementary Figure 2B](#SM2){ref-type="supplementary-material"}). This region has an I-TASSER predicted structure (Yang and Zhang, [@B90]) similar to that of a coiled-coil domain ([Supplementary Figure 2C](#SM2){ref-type="supplementary-material"}) which suggests the region may play a role in protein-protein interactions or oligomerization (Truebestein and Leonard, [@B83]). Notably, a 14-residue region of this domain (700--713 aa) ([Supplementary Figure 2B](#SM2){ref-type="supplementary-material"}, underline) is perfectly conserved amongst the predicted CP2 orthologs, even in the more distantly related *Paratrypansoma confusum* ([Supplementary Figures 2E](#SM2){ref-type="supplementary-material"}, [3](#SM3){ref-type="supplementary-material"}). This suggests that the region plays a significant role in the protein\'s function or targeting, as it is under significant selective pressure to resist even minor modifications. To test the potential role of this 45 aa conserved region of CP2 in SPC targeting, it was fused to the C-terminus of mNeon (mNeon-CP2ct) and transiently overexpressed in epimastigotes. We observed, via fluorescence microscopy, an SPC-like structure resulting in transfected parasites, suggesting a role for this region in targeting CP2 to the cytostome ([Supplementary Figure 2D](#SM2){ref-type="supplementary-material"}). The second protein of interest, CP3 (TcCLB.510679.40, NCBI Accession: [XP_807127.1](XP_807127.1)) exists as multiple copies in several *T. cruzi* strains (i.e. Sylvio, Dm28C, TCC) but was found to exist only as a single copy in the CL Brener strain. Orthologs of CP3 were present only in the closely related species to *T. cruzi*, as was observed with CP1. CP3 is predicted to be 455 aa in length with a molecular weight of 52 kDa and isoelectric point of 8.96. Unlike in CP1 and CP2, no identifiable domains were found within this protein sequence. We generated mutants overexpressing CP2-mNeon-Ty and CP3-mNeon-Ty and immunoblots revealed bands of \~110 kDa ([Figure 4C](#F4){ref-type="fig"}) and 60 kDa ([Figure 4D](#F4){ref-type="fig"}) respectively. The CP2 band matches the predicted molecular weight for CP2-mNeon-Ty (108 kDa), but the CP3 band is smaller than the 80 kDa predicted molecular weight, suggestive of post-translational processing that may affect its migration ([Figure 4E](#F4){ref-type="fig"}). In CP2-mNeon-Ty expressing epimastigotes, this protein presents a strong signal near the SPC entrance as well as along the tubule itself ([Figure 4E](#F4){ref-type="fig"}). CP3-mNeon-Ty also localized to the SPC in epimastigotes, but additionally localized diffusely to disparate areas of the cell which may be due to overexpression ([Figure 4F](#F4){ref-type="fig"}). The dispersed labeling of CP3 suggests a potential minor affinity for cytoskeletal microtubules when overexpressed (Angelopoulos, [@B6]) however because the most intense labeling is along the SPC it suggests that CP3 may be labeling one or both of the microtubule root fibers associated with the endocytic structure that can also be seen in [Supplementary Figure 4](#SM4){ref-type="supplementary-material"} (Kalb et al., [@B39]; Alcantara et al., [@B3]). To demonstrate the co-localization of CP2 and CP3 fusions to the SPC in amastigotes, we generated a polyclonal mouse antibody against a 240 amino acid antigenic region of CP1 recombinantly expressed in *E. coli* ([Supplementary Figure 5A](#SM5){ref-type="supplementary-material"}) (α-CP1). This region was identified through the combined use of the 7 IEDB antibody epitope prediction analysis methods (see Materials and Methods section). This region was further confirmed to not contain epitopes that had significant sequence similarity to other proteins in human cells or *T. cruzi*. This antigen (CP1Ag) was purified and isolated from the N-terminal tag prior to mouse inoculation ([Supplementary Figure 5B](#SM5){ref-type="supplementary-material"}). Immunoblots with α-CP1 recognized CP1-mNeon-Ty in lysates ([Supplementary Figure 5C](#SM5){ref-type="supplementary-material"}). The antibody was also capable of labeling endogenous levels of CP1 in IFAs of wildtype epimastigotes ([Supplementary Figure 5D](#SM5){ref-type="supplementary-material"}). Labeling of the SPC structure with α-CP1 demonstrated a clear overlap with both CP2 and CP3-mNeon-Ty in intracellular amastigotes ([Figures 4G,H](#F4){ref-type="fig"}). We observed a mild but significant difference in the growth rates of CP3-mNeon-Ty overexpressing epimastigotes relative to the parental line ([Supplementary Figure 6](#SM6){ref-type="supplementary-material"}). Discussion {#s6} ========== Here we report the identification and initial characterization of the first three known molecular components of the cyto[s]{.ul}tome/cyto[p]{.ul}harynx [c]{.ul}omplex (SPC) in *T. cruzi*. Given that the SPC is responsible for the endocytosis of extracellular material during the replicative epimastigote and amastigote stages, it is hypothesized to be a critical organelle for obtaining the necessary nutrients to support the high energetic demands of parasite replication. Our initial identification of CP1 was made possible by the recent development of efficient genomic modification tools (e.g., CRISPR/Cas9) in this parasite that we have employed in an ongoing protein localization screen. Our examination of endogenously tagged CP1-Ty showed its targeting to a linear structure seen only in the replicating forms and absent from the infectious stages, in line with previous examinations of the parasite endocytic structure (Vidal et al., [@B86]). In fluorescence-based protein feeding assays, CP1 co-localized with a variety of endocytosed cargo, confirming it to be a bona fide SPC resident protein. These studies highlighted the broad specificity of the SPC by showing that it was capable of shuttling BSA, IgG, Transferrin, and CFSE labeled host protein through this endocytic pathway. Surprisingly, we failed to observe any endocytosis of cargo, including albumin (BSA), via the flagellar pocket in our assays suggesting that the SPC may be the exclusive endocytic route for whole protein uptake in this parasite (Soares and de Souza, [@B75]; de Figueiredo and Soares, [@B20]; Kalb et al., [@B39]). The overexpression of a CP1-mNeon-Ty fusion demonstrated that neither targeting nor viability was compromised as a result of the large fluorescent tag. This fusion product facilitated the first analysis of the SPC under native conditions and showed that the near-linear stream of endocytosed cargo seen in our initial feeding assays may be, in part, an artifact of sample permeabilization as parasites free from this processing step contained a regular array of repeating vesicle-like structures along the CP1 labeled SPC organelle. This also suggested the presence of two distinct functional subregions in the structure labeled by CP1: a short funnel-shaped cavity at the entrance followed by an array of regularly spaced budded vesicles being trafficked to the lysosomes for digestion. Additionally, while images showing pre-oral ridge (POR) labeling by Concanavalin A has been shown in electron microscopy images (Martinez-Palomo et al., [@B55]; De Souza et al., [@B24]), this is the first demonstration of its use to label the POR in fluorescence light microscopy and this method can now be used to dissect this surface region\'s unique properties in future studies. In this and prior work, the POR often presents as a "sticky" patch on the cell surface where endocytosed cargo, even in the presence of endocytic blocking agents (e.g., CytB), binds specifically. Intriguingly, this POR region may function in a manner analogous to many free-living bacterivorous protozoa that coat the area around their cytostome entrance with lectins in order to enhance the capture of bacterial prey (Roberts et al., [@B69]; Wootton et al., [@B89]; Martel, [@B53]). It is tempting to speculate that, in addition to the organelle itself, *T. cruzi* may have retained surface receptor-like molecules to capture protein cargo and thus increase the efficiency of endocytosis like its predatory ancestors. Transmission EM analyses have also shown that the POR ridge surface membrane composition is distinctly lacking in transmembrane proteins yet is extremely glycan rich in comparison to the rest of the parasite membrane and appears to originate from the flagellar pocket itself (Martinez-Palomo et al., [@B55]). The river-like appearance of the POR membrane connecting the cytostome to the flagellar pocket suggests a potential mechanism to preserve overall membrane homeostasis whereby the membrane being "pulled" into the SPC originates from vesicle fusion events within the flagellar pocket itself (Souto-Padron and de Souza, [@B76]). A continued dissection of the role of the POR membrane and its associated surface proteins may shed light on how the process of SPC mediated endocytosis functions and is regulated. In this work we also report the initial characterization of SPC targeted proteins derived from IP and MS analyses. Associated with CP1, we identified two additional hypothetical proteins named CP2 and CP3 that target to the SPC as shown through co-localization with our in-house derived α-CP1 antibody. While the hypothetical nature of CP1, CP2, and CP3, make it more challenging to predict the role they play in endocytosis, future studies will involve the generation of either deletion or conditional knockdown mutants to elucidate their function. We suspect that CP2 may be the most important of the proteins for SPC function, due to the presence of an ortholog in its more distant relative, *P. confusum*. CP2 also presents a highly conserved C-terminal region of 14 perfectly conserved amino acids. This region may serve as either a trafficking signal or an important interacting domain that does not tolerate amino acid changes despite potentially hundreds of millions of years of divergent evolution. (Marks et al., [@B52]; Nishimura and Balch, [@B61]; van Hennik et al., [@B84]; Bedoukian et al., [@B9]; De Marcos Lousa et al., [@B21]; Starodubova et al., [@B78]). The C-terminal region\'s predicted similarity to a coiled-coil domain also lends credence to it serving a role in protein-protein interactions (Truebestein and Leonard, [@B83]). Continued mutagenesis and fusion protein studies with this domain will help uncover the functional significance of this conserved region. It is reasonable to expect that the SPC is composed of a variety of additional proteins that contribute to both its form and function and we believe that future in-depth characterizations of these proteins will increase our understanding of the *T. cruzi* endocytic machinery and its role in the parasite life cycle and pathogenesis. With this being the first report of proteins specifically targeted to the SPC structure in this or any organism, we now have the necessary tools to initiate an examination of the mechanistic underpinnings of this unique protozoan organelle. Data Availability Statement {#s7} =========================== All datasets generated for this study are included in the article/[Supplementary Material](#s9){ref-type="sec"}. Author Contributions {#s8} ==================== NC and RE designed and performed the experiments, analyzed the data, and generated the figures. IC performed immuno-electron microscopy experiments and analysis. RE and NC wrote the manuscript with author input. Conflict of Interest -------------------- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We thank Rick L. Tarleton for key biological materials and financial support; Roberto Docampo and Noelia Lander for reagents and advice in molecular manipulations of *T. cruzi*; Menna G. Etheridge for the production of *T. cruzi* life cycle graphics; Muthugapatti Kandasamy at the University of Georgia Biomedical Microscopy Core and Julie Nelson at the CTEGD Cytometry Shared Resource Lab for technical assistance. We would like to acknowledge the University of Georgia Proteomics and Mass Spectrometry (PAMS) facility. **Funding.** All sources of funding for this research are derived from the National Institutes of Health (NIH). This work was supported by an R21 exploratory grant (1R21AI146447) which supports an examination of the unique endocytic organelle of *Trypanosoma cruzi* as well as a post-doctoral T32 training fellowship (T32AI060546). Funding for publication fees are a part of the R21 exploratory grant budget. Supplementary Material {#s9} ====================== The Supplementary Material for this article can be found online at: <https://www.frontiersin.org/articles/10.3389/fcimb.2019.00445/full#supplementary-material> ###### SPC labeling is absent during cytokinesis and the trypomastigote stage. **(A)** Amastigote labeling of the SPC by CP1-mNeon (ii) is absent in amastigotes undergoing cytokinesis (i), determined by the presence of a cleavage furrow (red arrow) and two nuclei (asterisk). **(B)** The SPC labeling by CP1-mNeon seen in amastigotes (ii), is absent in a trypomastigote (i). Scale bars: 2 μm. ###### Click here for additional data file. ###### The highly conserved C-terminal region of CP2 is sufficient to traffic mneon to the cytostome/cytopharynx complex. **(A)** Cartoon showing CP2 and its predicted SMC domain over an amino acid scale line. The red line annotates the highly conserved C-terminal region (675--720 aa). **(B)** Alignment of the highly conserved C-terminal region. The black line identifies a notable 14 amino acid region that maintains 100% identity among all orthologs, even in the more distantly related *P. confusum*. **(C)** The ITASSER predicted structure of the conserved C-terminal region is similar to that of a coil-coil protein interaction domain. The confidence score (range −5.0 lowest to +1.0 highest) of the predicted structure is high at −0.7. **(D)** Fluorescence image of an epimastigote overexpressing mNeon fused to the 45 aa CP2 C-terminal region (see **B**) shows SPC labeling (arrow). **(E)** A bootstrapped Jukes-Cantor neighbor-joining tree analysis of CP2 orthologs using the alignment from [Supplementary Figure 3](#SM3){ref-type="supplementary-material"}. The weakly related potential ortholog from *B*. *saltans*, which is missing the C-terminal region entirely was used as the outgroup. Branches are labeled with their bootstrap value. ###### Click here for additional data file. ###### Alignment of CP2 orthologs for tree analysis. T-coffee alignment of the CP2 orthologs from *T. cruzi CL Brener* (NCBI: XP_807919.1), *T. cruzi Dm28c* (Genbank: [ESS69597.1](ESS69597.1))*, T.cruzi Sylvio* (Genbank: [EKG03371.1](EKG03371.1))*, T. cruzi Marinkellei* (Genbank: [EKF31948.1](EKF31948.1))*, T. rangelli* (Genbank: [ESL08911.1](ESL08911.1))*, T. Theileri* (NCBI: XP_028885643.1)*, P. confusum* (TriTrypDB: PCON_0003310)*, B. saltans* (Genbank: [CUG86305.1](CUG86305.1)). ###### Click here for additional data file. ###### CP3-mNeon labels structures reminiscent of the microtubule root fibers. Fluorescent image of the CP3-mNeon shows labeling of the microtubule root fibers associated with the paraflagellar region (arrow) and SPC. Scale bar: 2 μm. ###### Click here for additional data file. ###### In-house generated αCP1 antibody labels the SPC. **(A)** Amino acid sequence of the chosen CP1 antigenic region (blue) with the N-terminal tag from the Pet32 LIC/EK vector (red). The black underlined region is the portion of the N-terminal tag that remains with the antigen after thrombin cleavage. **(B)** Purification of CP1 antigen for antibody generation. CP1 antigen (blue arrow) in the primary elution from Ni^2+^ column is thrombin digested, which cleaves off the N-terminal tag containing the 6x histidines (red arrow). The digested eluate is then passed through a Ni^2+^ column again, followed by a gentle elution with 10 mM imidazole. Pure, 6xHis tag-free CP1 antigen (green arrow) was eluted by this step and this purified antigen was then used for mouse inoculation. **(C)** Immunoblot of Parental and CP1-mNeon-Ty overexpressing mutant lysates showing the labeling of CP1-mNeon-Ty by polyclonal mouse αCP1 antibody. **(D)** SR-SIM IFA of Y strain epimastigotes showing αCP1 labeling of the SPC. Scale bars: 2 μm. ###### Click here for additional data file. ###### Epimastigotes overexpressing CP3-mNeon exhibit a growth defect. **(A)** Growth assays of Parental (Y Strain), CP1-mNeon, CP2-mNeon, and CP3-mNeon epimastigotes. **(B)** Fold change in parasites during 48 h of exponential growth (24--72 h) shows a significant reduction in growth of the CP3-mNeon overexpressing mutants. ^\*^*p* \< 0.05. ###### Click here for additional data file. ###### Primers utilized in this work. ###### Click here for additional data file. [^1]: Edited by: Nobuko Yoshida, Federal University of São Paulo, Brazil [^2]: Reviewed by: Carlos A. Buscaglia, National Council for Scientific and Technical Research (CONICET), Argentina; Wanderley De Souza, Federal University of Rio de Janeiro, Brazil [^3]: This article was submitted to Parasite and Host, a section of the journal Frontiers in Cellular and Infection Microbiology | High | [
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LA-based multi-platform adult animation producer/distributor MONDO is bringing two very special programming treats to this year’s Rooster Teeth Animation Festival — taking place during RTX 2017 July 7-9 in Austin, TX (rtxaustin.com). Attendees will have a chance to see the English-language premiere of bold ‘n’ brawny graphic novel adaptation Lastman, as well as the global season 4 premiere of irreverent comedy Deep Space 69. The latter will accompany a special screening of Adult Swim’s Apollo Gauntlet, from MONDO’s Six Point Harness studio. “RTX is an incredibly exciting event, and their first-ever Animation Festival in 2016 proved to be so popular that it’s a perfect setting for us to show off our newest projects to an incredible group of fans,” said Brendan Burch, MONDO’s chief creative officer and president of Six Point Harness. A traditionally animated, visually bold graphic-novel adaptation, Lastman originally aired on France4 and has been translated into English in a multi-national creative effort. The series blends martial arts and boxing action with drama and supernatural elements into a unique adventure. On the more witty and whimsical side, Deep Space 69 — created by Daniel Katz (Xemoland, Beer Cops) is an intergalactic tale of sex, sexual exploits and sexual conquests, with the first three seasons racking up more than 50 million views online. Both series will be available exclusively on MONDO’s channel on VRV, the new video platform from Ellation. MONDO will host an hour-long panel at RTX featuring both Lastman and Dead Space 69, featuring a discussion with Six Point Harness prez Burch, head of development Wendy Willis, and creative director Greg Franklin on Sunday, July 9 at 11 a.m. (Room 10AB, Austin Convention Center). The Apollo Gauntlet screening will also be followed by a panel discussion hosted by Adult Swim, with series creator/voice star Myles Langlois with MONDO’s Willis, Franklin and lead editor Tony Christopherson on Saturday, July 8 at 4 p.m. (Center Stage, ACC). | High | [
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A student who posted “It’s Okay to be White” flyers outside of a building at the Oklahoma City University of Law was expelled and interrogated by the FBI Joint Terrorism Task Force. The Oklahoman reports: OCU Police Director Bill Citty said the male student was already on suspension from the law school, 800 N Harvey, and was not allowed to be on school property. The student violated the terms of his suspension when he posted the flyers on the door and exterior of the law school building the night of Oct. 31, Citty said. Jim Roth, the school’s dean, sent the perpetrator a letter informing him of his expulsion in mid November. The culprit, who remains anonymous, was serving a prior suspension for his Tinder profile, which stated a preference for a girl who “hasn’t been with a black guy.” “You have violated the terms of your suspension, which prohibited you from entering campus grounds. The University is in possession of evidence clearly demonstrating that you entered University grounds on or about October 31, 2019,” Roth’s letter read. “Based on a preponderance of the evidence, pursuant to the terms of your suspension, and according to University policy, you are hereby expelled from Oklahoma City University School of Law, effective immediately.” We can’t tell you the name of the host or it’ll make our authoritarian masters angry. Just submit, dirty Americans! Don’t think for yourself! Let establishment pundits do all the thinking for you! Just be a drone. Don’t share this broadcast! Also, get all you need to completely stuff Christmas stockings this year with our Christmas Mega Pack sold AT COST during the 12 Days of Christmas Sale! The letter reiterated the student’s ban from campus and threatened legal action if the student ever comes back. Roth also issued an ironic public statement praising students who ripped down the posters and notified school officials. “Despite what the intentions of that message may have been, the message reminds me of one fact that I know our community embraces – it’s okay to be EVERYBODY,” he wrote. “Exclusion and hate will not be tolerated here. You are accepted at OCU Law no matter how you pray, what you look like, or who you love. And you always will be.” That message, the student said, doesn’t apply to white students who aren’t ashamed of their skin color. The student told The Red Elephants’ Vincent James he was interrogated by an agent with the FBI’s Joint Terrorism Task Force, who confirmed the posters were not a crime. The agent also told the student, who was dressed up for Halloween when he posted the flyers, there is no possible way for law enforcement to positively identify him from surveillance video, even if it was illegal. “He basically said no crimes were committed, we just got to make sure you’re not a threat,” the student said. “Both the FBI and the Oklahoma City Police said … we have no reason to open an investigation, we’re not considering you a suspect of any crime, but the campus police, the private police they have at the school, I guess if they wanted to they could press trespassing charges.” National File contacted another “It’s Okay to be White” activist for another perspective on the debacle, which he claims is an illustration of the double standard for racism in America. “My only thoughts on this incident are that the response was draconian and hysterical (but sadly predictable) and should serve as a wake-up call to anyone who does not want to live under totalitarianism. The people who want to ruin this young student’s life for refusing to hate himself are evil,” the unidentified activist said. “The response also clearly demonstrates a racial hatred and paranoid fear of white people deeply rooted in the establishment media, academia and government, not only in the US but across the West,” he said. “If you replaced the word ‘white’ with any other group and put up a flyer saying ‘It’s Okay to be (another group),’ there would likely have been no police attention or media coverage,” he said. “This law student who was expelled is essentially a martyr. He sacrificed years of study, large sums of money and part of his reputation and future to warn people about this totalitarian threat.” The Emergency Election Sale is now live! Get 30% to 60% off our most popular products today! | Low | [
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The centre back retains a strong sense of community spirit and tries to give back to causes which can help people worse off than him Gabriel insists that the two now have a positive relationship A high-profile incident between them saw Gabriel sent off this season He has been involved in a couple of spats with striker Diego Costa The Brazilian has come a long way in his football career Gabriel laughs, screws up his eyes, shakes his head and then buries it in his hands, in embarrassment. Diego Costa is the subject. Not the infamous clash at Stamford Bridge last September, which saw Costa feign an injury to get the Arsenal defender sent off, a red card which was later overturned. This is an earlier clash, with Costa in the colour of Atletico Madrid and Gabriel playing for Villarreal. Costa does swing an arm at Gabriel but it barely makes contact and the Villarreal man collapses to the floor in agony. Arsenal defender Gabriel has come a long way since his days growing up in an impoverished favela The 25-year-old centre back signed for Arsenal from Villarreal last January for a reported £11.2m fee To his credit, he does seem genuinely mortified when it is brought up and looks pleadingly at his inquisitor. 'When we are on the pitch we are different people,' says the 25-year-old centre-half, signed from Villarreal for £11.2million last January. 'Diego is a different person and so am I. When we clash there are sparks!' Indeed. Both Brazilian born, though Costa has since opted to play for Spain, the country to which he moved to play football, they share a common spirit. Neither is likely to walk away from a confrontation, regardless as to whether it concerns them or not. The original furore with Costa had been sparked by the Chelsea player barging over Laurent Koscielny. Gabriel wouldn't stand for that and immediately sprung to his team-mate's defence, physically remonstrating with Costa. To some, it seemed a welcome addition to Asrenal's collective identity, a streetwise fighter ready to go toe to toe with Chelsea; except that he ended up being suckered into being sent off. 'That's how I am,' says Gabriel. 'I will always stand up for the ones I love. We have affection for our team mates because we spend most of our time with them. Sometimes we spend more time with our team-mates than our families. This is my instinct I always stand up for my team-mates. 'For me, the red card was a surprise but I learned from that experience. I won't change. That's how I react in these situations but I learned and I will defend my team-mates but in another way — not doing what I did.' What he said to Costa is apparently unprintable. 'It was an affectionate exchange!' he says. 'It's something that happens in a football match. It was in the moment.' Gabriel was shown a red card earlier this season after an altercation with Chelsea striker Diego Costa (left) Gabriel has since insisted that he and Costa have buried the hatchet and now have a good relationship Gabriel is donating a day's wages along with his team-mates to the Arsenal Foundation, which supports causes including Save the Children And it seems they have kissed and made up. Gabriel is now in the Brazilian national squad and shares a mutual friend with Costa in Filipe Luis, the former Chelsea left back. 'We have turned that page. 'I was in the Brazil squad with Filipe Luis and those two are good friends. I sent him a voice message as a friend. We are good friends. It's something that happens on the pitch and it is passed. Diego is a good person.' However, he rejects any suggestion that Costa, raised in Lagarto, a remote town in the northern Brazilian Savannah, has much in common with him. 'I wouldn't say we are similar just because we came from a poor background,' says Gabriel, who grew up in the Sao Paulo favela of Capao Redondo. 'Really, Sao Paulo is a lot worse than Lagarto!' Gabriel's remains proud of his community and still contributes financially to the youth football team for which he played there but he does not sugarcoat the experience. 'We didn't have water in our pipes and electricity we took from the mains cables. I've seen many bad things, I was robbed. I've seen crimes. Gabriel has opened up about his difficult childhood and is grateful to now know his family are safe Gabriel's rags-to-riches rise has given him a fresh perspective in life and he wants to give back to his roots 'In the beginning it was quite tough, we had to live in such difficult conditions. I had to see things that I don't want to see ever again. It was a violent environment. That situation made me feel stronger to achieve success in football, that's what I always dreamt of. 'I was trying to fight for my family, my mother [Terezinha] was in need at that time. So football was the only way I could help her. I had five siblings [he is the youngest of Jose Marcos, Marcos Antonio, Ana, Paulo, Rafael] and they were all working but I was the only one who could help my mother. I wouldn't say that I suffering from being hungry but it was difficult to put a meal on our plates, to have a proper meal in our house, so football was the only way to help my mother. 'I was privileged, because I'm the youngest kid in my family so when I was born things were better for me. My dad [Silvio] and my siblings used to live in a house made from wood in the favela. They lived in houses like that but I didn't. When I was born we lived in a brick house. 'In my time we just had football and school. Those were the only activities we had to do. We didn't have any other option. It was very difficult, because all of my other friends, they didn't have any options. If you don't succeed in football, you don't have any options to have a life. 'Nowadays it's getting better because the mayor of Sao Paulo built a community centre, so they have dance class, language class, we have music classes. So now the kids they have more options. If they like to dance, they can go there to have classes; if they like football, they have a football teacher for them. 'Today they have more options but in my time we just had football. In my time we had the football pitch without grass, we had a mud pitch.' Gabriel's early footballing experiences were far more modest than life in the Premier League Gabriel, in action for Arsenal in the Champions League, dribbles with the ball against Olympiacos He has since discovered that his Brazilian team-mate and Chelsea opponent Willian often used to play on the same pitch.' An early trial for Santos didn't work out but a call up for a local team, Taboao de Serra, the Sao Paulo cup and impressive performance against Vitoria saw him move to the top-flight club in north east Brazil, where Bebeto and David Luiz had also played. Earning good wages though didn't help him escape the violence of his youth, but merely attracted trouble. 'I was robbed when I was young and playing for Vitoria, it was my first professional team. I was withdrawing money from the cashpoint and they followed me on a motorbike and stole my money. It was not my whole salary but it was a lot of money by Brazilian standards.' He has moved his parents to a house outside Sao Paulo, with kidnapping of relatives an all-too-real fear for South American players. Gabriel, pictured here during his spell at Vitoria, escapes the tackle of Corinthians' Ronaldo (right) 'When I was in Vitoria it was OK to let my parents live in that community but now I'm playing for Arsenal and I've been called up from Brazil things are more dangerous for my family so now I have bought a house for my family in a different area, outside of Sao Paulo. 'I'm worried about them being kidnapped. It worries me a lot. I'm playing and I need to be focused on football and this was worrying me a lot.' Yet he maintains his connection with Capao Redondo. 'In my time my football club as a boy we were always getting invitations to play in the countryside around Sao Paulo against the other academies and we never had money to pay for travel expenses. 'So now I pay for the expenses and the fee to be part of the tournament and give them back what they gave me.' Along with his Arsenal team-mates, he is also donating a day's wages to the Arsenal Foundation, which supports causes including Save the Children, with whom Arsenal are building football pitches in refugee camps in Iraq. 'It's pure joy,' he says. 'As a footballer it is our duty to help people because someone helped us.' Footballers' endorsements of the charities they support can sometimes feel trite; Gabriel's sounds as if he means it. Arsenal's match against Manchester City on Monday is dedicated to The Arsenal Foundation. | Mid | [
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1. Introduction {#sec1-jcm-09-01853} =============== Breast cancer therapies are driven by tumour biology with four main intrinsic molecular subtypes of breast cancer that show substantial differences in phenotype, prognosis, treatment response, and survival \[[@B1-jcm-09-01853],[@B2-jcm-09-01853],[@B3-jcm-09-01853],[@B4-jcm-09-01853]\]: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple negative (TN) \[[@B5-jcm-09-01853],[@B6-jcm-09-01853]\]. In clinical practice, the assessment of molecular subtypes for treatment planning is mostly performed from immunohistochemical surrogates from invasive tissue sampling \[[@B3-jcm-09-01853]\]. Nevertheless, this approach is potentially flawed, as a biopsy can only deliver a small amount of tissue, while genetic heterogeneity within a single tumour is a major cause of therapy resistance and treatment failure \[[@B7-jcm-09-01853],[@B8-jcm-09-01853],[@B9-jcm-09-01853],[@B10-jcm-09-01853]\]. Furthermore, genetic profiling is performed at a single time point, although tumour biology might potentially change over time and with treatment \[[@B11-jcm-09-01853]\]. The rapidly evolving field of radiomics is based on the assumption that tumour biology is reflected in microstructural patterns within medical imaging, some of which the human eye cannot perceive. Recent advances in biomedical image acquisition, high-throughput methods for analysis, and the application of artificial intelligence (AI) have improved the quantification of these radiomic features, which may non-invasively provide information for a given tumour in its entirety. In this context, radiomics coupled with AI has the potential to improve patient stratification, treatment planning, and therapy monitoring, and may be combined with clinical and genomic data to achieve the overarching goal of precision medicine. Previous radiomics studies in breast imaging have primarily focused on features derived from dynamic contrast-enhanced MRI (DCE-MRI), with promising results for the non-invasive identification of different types of breast cancer \[[@B12-jcm-09-01853],[@B13-jcm-09-01853],[@B14-jcm-09-01853]\]. Although multiparametric MRI, including DCE-MRI and diffusion-weighted imaging (DWI), is widely recommended, \[[@B15-jcm-09-01853]\] data are scarce on DWI radiomic signatures and their utility in this context \[[@B16-jcm-09-01853],[@B17-jcm-09-01853]\]. Few prior studies have evaluated combined multiparametric MRI with DCE-MRI and DWI radiomics signatures in the breast; however, the generalisation of these findings is limited due to the use of different imaging protocols and scanners \[[@B18-jcm-09-01853]\], the investigation of histogram features only \[[@B19-jcm-09-01853]\], and the lack of advanced artificial intelligence-based machine learning algorithms for analysis \[[@B18-jcm-09-01853],[@B19-jcm-09-01853]\]. We hypothesised that microstructural differences between breast cancer subtypes exist that can be captured with multiparametric MRI radiomics and classified using AI. Therefore, the purpose of this study was to evaluate the performance of radiomics and AI from multiparametric MRI for the assessment of breast cancer receptor status and molecular subtypes. 2. Material and Methods {#sec2-jcm-09-01853} ======================= This retrospective single-institution study is in accordance with Health Insurance Portability and Accountability Act guidelines and was approved by the Institutional Review Board with a waiver for written informed consent. 2.1. Patients {#sec2dot1-jcm-09-01853} ------------- A database search was conducted for patients who underwent multiparametric MRI of the breast including DCE-MRI and DWI between January 2011 and January 2013, and who met the following inclusion criteria: histopathologically verified breast cancer; patient age, 18 years or older; and lesion size, greater than 1 cm on DCE-MRI to reduce the influence of the partial volume effect on the radiomics analysis. The exclusion criteria were as follows: other types of breast cancer besides invasive ductal carcinoma, a personal history of other cancers, a high risk status, prior systemic cancer treatment, pregnancy or breast-feeding at the time of MRI, poor MR image quality, and artefacts leading to signal distortions in the tumour area, as assessed by a board-certified radiologist specialising in breast imaging. Thus, 91 patients were included in this study. 2.2. MR Imaging {#sec2dot2-jcm-09-01853} --------------- All MRI examinations were performed using a 3 Tesla scanner (Discovery MR750; GE Healthcare, Milwaukee, WI, USA) with a body coil as the transmitter and a dedicated 16-channel phased-array breast coil (Sentinelle Vanguard, Toronto, ON, Canada) as the receiver. The state-of-the-art MRI protocol consisted of the following pulse sequences: a T2-weighted imaging sequence with and without fat suppression (fast spin-echo sequence; TR/TE, 4.384/102 ms; auto flip angle, 111°; matrix size, 288 × 224; FOV, 30 cm; slice thickness, 3 mm; NEX, 2; acquisition time, approximately 3.5 min); a 2D, single-shot, dual spin echo-planar DWI sequence (TR, 6.000 ms; minimum TE; flip angle, 90°; acquisition matrix, 98 × 98 or 128 × 128; reconstructed matrix, 256 × 256; FOV, 28--38 cm; slice thickness, 4 or 5 mm; NEX, 3; slice gap, 0--1 mm; fat suppression, enhanced; parallel imaging, ASSET; acquisition time, approximately 2 min for two b-values of 0 and 1000); and a DCE-MRI sequence with and without fat suppression (3D T1-weighted gradient echo VIBRANT sequence; TR/TE, 4.3/2.1 ms; flip angle, 10°; matrix size, 320 × 192; FOV, 30 cm; 1.0 mm slice thickness; NEX, 1; acquisition time, approximately 1 min). The DCE-MRI series were acquired before and at three points at 60 s intervals after a standard dose (0.1 mmol/kg body weight) of gadopentetate dimeglumine (Magnevist; Bayer HealthCare, Hanover, NJ, USA) was injected intravenously as a bolus, followed by a saline flush. 2.3. Radiomics Analysis {#sec2dot3-jcm-09-01853} ----------------------- The first post-contrast T1-weighted sequence and the apparent diffusion coefficient (ADC) map were used for radiomics analysis. Feature extraction was performed semi-automatically using the open-source software MaZda 4.6 (<http://www.eletel.p.lodz.pl/programy/mazda/>). Two radiologists with 13 and four years of experience analysed images in consensus. A single two-dimensional region of interest (ROI) covering the whole tumour on the DCE-MRI section depicting the largest transaxial lesion diameter was drawn manually. Texture parameters were extracted from the DCE images on the one hand, and from the ADC maps on the other hand. Due to the better contrast between the lesion and the surrounding tissue, the ROI was drawn on the DWI images but then copied to the ADC map; the texture features were then extracted from this ROI on the ADC map (i.e., not from the DWI images). A minimum distance of 2 mm was kept from any biopsy markers present. Artefacts were excluded from segmentation. Grey-level normalisation was performed (dynamics, µ ± 3σ; µ, grey-level mean; σ, grey-level standard deviation) to reduce contrast and brightness variations that might impair texture feature quantification \[[@B20-jcm-09-01853]\]. All the radiomic features that MaZda was capable of calculating were included, resulting in a total number of 704 features per lesion. Features derived from various classes, such as the first-order histogram (*n* = 18), lesion geometry (*n* = 146), absolute gradient (*n* = 10), autoregressive model (*n* = 10), co-occurrence matrix (n = 440), run-length matrix (n = 40), and discrete Haar wavelet transform (*n* = 40) were calculated (see <http://www.eletel.p.lodz.pl/programy/mazda/download/FeaturerList.pdf> for full feature list). Radiomic features represent a multitude of tissue characteristics such as shape, heterogeneity, intensity, and local interactions between pixels. The total time of lesion segmentation and radiomics analysis was approximately 5 min per patient. 2.4. Statistical Analysis {#sec2dot4-jcm-09-01853} ------------------------- Out of the large number of features obtained, the five most relevant features for the differentiation of molecular subtypes were selected separately for each technique (i.e., DCE-MRI and DWI). For this study, the minimisation of the probability of error and average correlation coefficients (POE + ACC) were used for feature selection. Contrary to other criteria such as Fisher coefficients, POE + ACC takes interrelationships between features into account with the aim of reducing data redundancy \[[@B21-jcm-09-01853]\]. Feature selection was performed once across the training dataset prior to radiomics-based classification. Histopathology served as the standard of reference. To differentiate between two groups with more than twenty patients each, a multi-layer perceptron feed-forward artificial neural network (MLP-ANN), which is based on a back-propagation learning algorithm, was used. For each pairwise classification, 70% of the respective cohort were used for training and 30%, for validation. Classification was performed five times for each pairwise comparison, as the starting point of an MLP-ANN is an initial guess at the weights of single features. For each repetition of the classification step, patients were randomly assigned anew to the training or validation dataset. A minimum of one hidden layer with a minimum of three neurons per hidden layer was used for the neural network. Areas under the receiver operating characteristic (ROC) curves (AUCs), as well as the diagnostic accuracies for the training and validation datasets, were calculated. The MLP-ANN was applied using SPSS 24.0 (IBM Corp., Armonk, NY, USA). For the separation of two groups with fewer than twenty patients each, linear discriminant analysis (LDA) was used for feature reduction, producing so-called "most discriminating features" (MDF). Hereafter, leave-one-out cross validation (LOOCV), as implemented in the B11 module of the MaZda 4.6 software, was applied for radiomics-based pairwise classification, i.e., training was performed using all patients except one, excluding information from the held-out patient, and testing was conducted on the remaining patient. This process was repeated n times, with n being the number of subjects in each comparison. 2.5. Histopathological Analysis {#sec2dot5-jcm-09-01853} ------------------------------- Tumour histology, tumour and nuclear grade, and immunohistochemical status including oestrogen receptor, progesterone receptor, and HER2 status were derived from final histopathological results from surgical tumour specimens. Oestrogen or progesterone receptor-positive tumours with over 1% staining were classified as hormone receptor (HR)-positive. Tumours were classified as luminal A for HR-positive and HER2-negative, luminal B for HR-positive and HER2-positive, HER2-enriched for HR-negative and HER2-positive, and TN for HR- and HER2-negative \[[@B22-jcm-09-01853]\]. In the case of equivocal HER2 status, lesions were additionally evaluated using fluorescence in situ hybridisation and classified as positive when gene amplification was detected. 3. Results {#sec3-jcm-09-01853} ========== Of the 91 treatment-naïve, biopsy-proven breast cancers, 57 were HR positive (62.6%). Forty-nine cancers were classified as luminal A (53.8%), eight as luminal B (8.8%), 11 as HER2-enriched (12.1%), and 23 as TN (25.3%). There were 70 mass lesions and 21 non-mass enhancing lesions on DCE-MRI. The mean lesion size was 3.5 ± 2.3 cm (range, 1--16.6 cm). The mean patient age was 48 ± 9.7 years (range, 27--68 years). In four pairwise classifications, the group sizes were large enough, i.e., there were over 20 patients in each group, and thus, the MLP-ANN was used, while for all other analyses, LDA and LOOCV were applied. AUCs higher than 0.8 and accuracies above 80% were considered to be sufficient for possible clinical application in terms of the assessment of molecular subtypes and HR status. Best results in terms of AUCs were achieved for the differentiation of TN cancers from other groups and luminal A cancers from other groups ([Table 1](#jcm-09-01853-t001){ref-type="table"}). The MLP-ANN yielded an overall median AUC of 0.86 (0.77--0.92) for the separation of TN from all other cancers ([Figure 1](#jcm-09-01853-f001){ref-type="fig"}), with median accuracies of 85.9% in the training dataset and 85.2% in the validation dataset. For the separation of these subtypes, a balanced mix of features from different categories such as histogram, texture, shape-based, and model-based, proved to be of importance ([Table 2](#jcm-09-01853-t002){ref-type="table"}). The discrimination of luminal A from TN cancers yielded an overall median AUC of 0.8 (0.75--0.83), with median accuracies of 74% in the training dataset and 68.2% in the validation dataset. Again, a balanced mix of features from different feature groups was useful for lesion classification. Hence, luminal A and TN cancers seem to carry distinct radiomic characteristics that enable their separation from other breast cancers ([Figure 2](#jcm-09-01853-f002){ref-type="fig"}). All other AUCs were below 0.8, and diagnostic accuracies, below 80% ([Table 3](#jcm-09-01853-t003){ref-type="table"}). 4. Discussion {#sec4-jcm-09-01853} ============= In this study, we assessed the performance of multiparametric MRI-based radiomics in conjunction with AI for the assessment of breast cancer receptor status and molecular subtypes. Our results indicate that radiomics signatures derived from multiparametric MRI enable the determination of certain treatment-naïve molecular breast cancer subtypes with high accuracy. Although radiomics and AI are unlikely to replace invasive tissue sampling, multiparametric radiomics imaging biomarkers could potentially serve as auxiliary parameters and a non-invasive method to derive prognostic and predictive information from the entire tumour before and during treatment. In the present study, the best results in terms of accuracies were achieved for the radiomics-based separation of TN from all other cancers, as well as luminal A and TN cancers (AUCs, 0.80 and 0.76). TN is the most aggressive type of cancer and carries a worse prognosis in comparison to the other subtypes. While patients with luminal A cancers may be offered endocrine therapy in addition to surgery and radiation treatment, and patients with HER2-positive cancers may receive additional targeted treatment with monoclonal antibodies, patients with TN cancers currently have no available targeted treatment \[[@B4-jcm-09-01853]\]. After additional validation, these specific results of our study might have direct clinical consequences, as they might prevent the exclusion of patients from adequate therapy when a heterogeneous tumour is present. The relevant information of tumour heterogeneity and the expression of HER2 or HR might otherwise go unnoticed, as biopsy can only deliver a small amount of tissue, and after neoadjuvant chemotherapy, no cancerous tissue for analysis might be available anymore. Previous radiomics studies in breast imaging have primarily focused on signatures extracted from DCE-MRI and their utility e.g., for the separation of benign and malignant lesions \[[@B23-jcm-09-01853],[@B24-jcm-09-01853]\], the prediction of treatment response \[[@B25-jcm-09-01853]\], and the separation of molecular subtypes \[[@B26-jcm-09-01853],[@B27-jcm-09-01853]\], with mixed results, which might be attributed to heterogeneity in scanners, sequences, and features. Holli-Helenius et al. reported AUC values of 0.83--0.88 for the differentiation of luminal A from luminal B cancers in a small patient collective using only co-occurrence matrix features \[[@B28-jcm-09-01853]\], while in the present study, the separation of luminal A from TN tumours based on features from different groups was more successful. Surprisingly, in times of the controversy regarding the application of gadolinium-based contrast agents \[[@B29-jcm-09-01853],[@B30-jcm-09-01853]\], data are scarce on radiomic features derived from DWI, with results from a single study suggesting that they might be useful for the assessment of breast cancer subtypes \[[@B31-jcm-09-01853]\]. Multiparametric breast MRI combining both DCE and DWI is increasingly used in clinical routine practice and is recommended to improve diagnostic accuracy, tumour characterisation, and response assessment \[[@B15-jcm-09-01853]\]. Although we acknowledge that, to date, it is not possible to adequately identify molecular subtypes using imaging alone, initial hints at underlying tumour biology may be found, such as rapid wash-out, rim enhancement, and a higher ADC in TN tumours \[[@B32-jcm-09-01853]\]. These imaging patterns can also be easily captured and quantified with radiomics analysis \[[@B33-jcm-09-01853]\]. In the pairwise comparisons achieving an AUC \>80% in our study, a very balanced mix of histogram, texture, shape-based, and model-based features seemed to be of importance for radiomics-based lesion classification, which emphasises the complementary value of the combination of MRI sequences to capture different functional aspects of tumour biology (e.g., diffusivity and perfusion). In the first study to investigate the value of multiparametric MRI radiomic signatures in this context, Sun et al. achieved excellent accuracies of up to 97.7% for the separation of subtypes in 107 patients \[[@B18-jcm-09-01853]\]. Notably, the authors relied on a small number of features and used Fisher discriminant analysis in a less advanced machine learning approach than the MLP-ANN used in the present study. Meanwhile, Xie et al. evaluated histogram features derived from multiparametric MRI for the differentiation of TN cancers from other subtypes in 134 patients, yielding AUCs of up to 0.76 \[[@B19-jcm-09-01853]\]. These results are in good agreement with our findings; nevertheless, their applicability is limited, as histogram features alone cannot provide true textural information in terms of the relationships between single pixels/voxels of a tumour \[[@B21-jcm-09-01853]\]. Clearly, rigorous standardisation in terms of image acquisition and analysis across institutions, or the use of deep learning neural networks in very large heterogeneous datasets, will be essential to enable the widespread application of radiomics in clinical practice. To our knowledge, this is the first study to examine the utility of combined DCE-MRI and DWI radiomic signatures for the differentiation between breast cancers of different molecular subtypes/receptor status using a strictly homogeneous imaging protocol and an advanced neural network. This study has limitations beyond its retrospective single-centre approach, which have to be acknowledged. First, all tumours were segmented manually and on the slice with the largest diameter only, which might not be feasible in the analysis of very large datasets. Furthermore, this approach might not capture tumour heterogeneity in its entirety, and it is therefore quite possible that better results might have been achieved with 3D texture features. Second, all ROIs were defined on high b-value DWI and transferred to the ADC map, although tumour segmentation directly on ADC maps has previously shown to be slightly beneficial for radiomics analysis \[[@B31-jcm-09-01853]\]. However, some lesions could not be confidently identified based on ADC maps alone and thus this approach was chosen. Third, although MLP networks are well-established powerful machine learning algorihms, even more advanced deep learning techniques such as convolutional neural networks with larger numbers of hidden layers and interconnections between neurons may have performed better. However, the complexity of these advanced algorithms used on a relatively small patient collective such as our own would have increased the possibility of overfitting and reduced generalisability. MLP networks are even increasingly recommended as they are high-performing, reliable, and robust models for classification tasks \[[@B34-jcm-09-01853]\]. Finally, the same patient cohort as in a previous study was used \[[@B31-jcm-09-01853]\]; however, there were major differences from a methodological point of view: (1) All classifications in the present study were based on a mix of DCE-MRI and DWI features, i.e., unlike in the previous study, DWI features were never used on their own, and only a subset of DWI features was used. This combined DCE + DWI approach, which aims for a more holistic representation of tumour biology by taking both tissue perfusion and diffusivity into account, therefore represents an extension of our previously published results. (2) The main results of the present study are based on a machine learning algorithm---an MLP neural network---that is clearly more advanced than the approach used in our previous study. The MLP-ANN requires the true separation of training and validation data and therefore provides a more realistic assessment of model performance. In conclusion, the results of study indicate the potential of radiomic signatures from multiparametric MRI with DCE-MRI and DWI to allow the separation of aggressive and non-aggressive subtypes (i.e., TN and luminal A) with high accuracy. Radiomic characteristics derived from multiparametric MRI might have the potential to yield imaging biomarkers and thus may be used to monitor tumour biology changes during treatment and, hence, provide decision support. Further studies with larger patient numbers using even more advanced neural networks are warranted to validate these initial findings and fully elucidate the potential of radiomics and AI in this context. The authors acknowledge the support in manuscript editing from Joanne Chin. Conceptualization, M.E.M. and K.P.; data curation, M.E.M. and D.L.; formal analysis, M.E.M. and D.L.; funding acquisition, K.P. and E.A.M.; investigation, D.L. and K.P.; methodology, M.E.M., D.L., and K.P.; project administration, K.P.; resources, K.P., D.F.M., E.A.M., and S.B.T.; software, M.E.M. and K.P.; supervision, E.A.M.; validation, M.E.M.; visualisation, D.L.; writing---original draft, D.L.; writing---review and editing, M.E.M., K.P., and M.S.J. All authors have read and agreed to the published version of the manuscript. This work was supported in part through the NIH/NCI Cancer Center Support Grant P30 CA008748, a grant from the Susan G. Komen Foundation, and a grant from the Breast Cancer Research Foundation. All funding sources had no involvement in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication. Maxine S. Jochelson has received speaker honoraria from GE Healthcare. Katja Pinker received payment for activities not related to the present article including lectures, service on speakers bureaus, and for travel/accommodation/meeting expenses from the European Society of Breast Imaging (MRI educational course, annual scientific meeting), IDKD 2019 and Siemens Healthineers. Katja Pinker has also been supported in part by the Austrian Nationalbank \"Jubiläumsfond' Project Nr. 16219, the 2020---Research and Innovation Framework Programme PHC-11-2015 Nr. 6672112, and seed grants from Siemens Austria, Novomed and Guerbet, France. Marius E. Mayerhoefer has received speaker honoraria and research support from Siemens Healthineers, and speaker honoraria from Bristol-Myers Squibb. All other authors declare that they have no conflicts of interest. {#jcm-09-01853-f001} {#jcm-09-01853-f002} jcm-09-01853-t001_Table 1 ###### Mean classification accuracies for radiomics data. --------------------------------------------------------------------------------------- Training Accuracy\ Test Accuracy\ AUC\ Median (Range) % Median (Range) % Median (Range) % -------------------------- -------------------- ------------------- ------------------- Luminal A vs. TN 74 (70--86) 68.2 (63.6--81.8) 0.8 (0.75--0.83) Luminal A vs. all others 65.6 (62.5--78.6) 66.7 (59.3--74.1) 0.72 (0.7--0.74) TN vs. all others 85.9 (78.1--91.3) 85.2 (85.2--90.9) 0.86 (0.77--0.92) HR+ vs. HR− 64.7 (63.2--80.9) 60 (52.2--82.6) 0.69 (0.63--0.89) --------------------------------------------------------------------------------------- Note: AUC, area under the curve; HR, hormone receptor; TN, triple negative. jcm-09-01853-t002_Table 2 ###### Selected feature sets for pairwise classifications with areas under the curve higher than 0.8. TN vs. All Others Luminal A vs. TN ----------------------------------------- ---------------------- ------------------ **DCE-MRI** Sum of squares Sum of squares Vertical coordinate of gravity centre Theta 2 Vertical second order moment of inertia GeoFmax/GeoFmin Theta 2 Danielsson ratio Histogram's variance Histogram's variance **ADC map** Difference entropy Sum of squares Sum average Difference variance Absolute gradient skewness Theta 2 Difference variance Difference variance Sum of squares Histogram's skewness Note: ADC, apparent diffusion coefficient; DCE-MRI, dynamic contrast-enhanced MRI; TN, triple negative. jcm-09-01853-t003_Table 3 ###### Results of group-wise radiomic feature-based classifications for molecular breast cancer subtypes using linear discriminant analysis and leave-one-out cross validation. HER2 Negative Luminal A Luminal B HER2-Enriched TN All Others --------------- --------------- ----------- ----------- --------------- ------- ------------ HER2 positive 67.7% \- \- \- \- 67.7% Luminal A \- \- 52.6% 56.7% \- \- Luminal B \- 52.6% \- 57.9% 38.7% 58.2% HER2-enriched \- 56.7% 57.9% \- 70.3% 54.9% TN \- \- 38.7% 70.3% \- \- All others 67.7% \- 58.2% 54.9% \- \- Note: HER2, human epidermal growth factor receptor 2; TN, triple negative. | High | [
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China's Oldest Science and Tech Publication Accepts BTC for Subscriptions On Sunday China’s oldest tech media publication, Beijing Sci-Tech Report (BSTR) also known as ‘Technology life,’ has announced the business is accepting bitcoin core (BTC) for the magazine’s 2019 subscriptions. Also read: Launching a Website on the Bitcoin Cash Network Is Now a Reality The Publication Beijing Sci-Tech Report Now Accepts BTC for 2019 Subscriptions The Beijing Sci-Tech Report (BSTR) is one of the oldest science and technology publications in China. The media organization prints editorials stemming from its ‘Technology Life‘ team of authors, and it also publishes approved content from the well known US science journal Popular Science. This weekend the magazine has announced that it will be accepting BTC for subscriptions towards its 2019 publications. The cost to subscribe to BSTR will be 0.01 BTC (about 450 yuan or $65 USD). The Beijing based publication has written reports on cryptocurrencies in the past and the use cases of blockchain technology. According to the press release, the announcement to accept BTC was brought about by the magazine’s desire to promote blockchain technology in a real-world setting for “practical actions.” “For a long time, blockchain technology has also been the object of in-depth tracking reports offered by Beijing Science and Technology Report and Technology Life,” the magazine’s press release details. Embracing the Payment Technology in Order to Cultivate New Readers One interesting fact about BSTR accepting bitcoin, the firm says, is that if the price of BTC grows significantly by 2020, they will also offer some refunds to those who have subscribed using the digital currency. A translated BSTR statement explains the publication hopes to “cultivate new readers” by embracing the payment technology. Beijing Sci-Tech Report is not the only publication that has tried to entice readers by accepting cryptocurrencies. Back in 2014 Time Incorporated announced accepting BTC through Coinbase for subscriptions to Fortune, Good Health, Travel and Leisure, and This Old House. In April of the same year, the Chicago Sun-Times also revealed it would accept BTC for payments. However, both publishing companies have since removed the BTC payment option. Beijing Sci-Tech Report being a technology-oriented magazine may have better luck than its periodical predecessors. What do you think about Beijing Sci-Tech Report (BSTR) accepting BTC for 2019 subscriptions? Let us know what you think about this story in the comment section below. Images via Shutterstock, BSTR, and Pixabay. Want to create your own secure cold storage paper wallet? Check our tools section. | Mid | [
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Induction of popliteal lymph node enlargement and antibody production in the mouse by pyridylallylamines related to zimeldine. The role of the para-brominated phenyl ring of the allylamine antidepressant drug, zimeldine, in its immunomodulating activity was studied by comparing local lymph node responses of mice to analogues with various phenyl ring substituents. The compounds (1.0 mg) were injected into the hind footpad and weight and cell number of the popliteal lymph node (PLN) and antibody production by PLN cells were determined 7 days later. Zimeldine and the para-trimethylsilylated and ortho-para-chlorinated compounds induced a marked PLN weight gain in C57BL/6 mice. The para-chlorinated and meta-brominated analogues were significantly less effective, while the para-fluorinated and the unsubstituted analogue failed to trigger PLN weight gain. The same range of potency of the compounds was seen when increases of PLN cell number in BALB/c mice and increases of IgM production by a fixed number of BALB/c PLN cells were determined. The IgG production on a per cell basis was not increased by the fluorinated and the unsubstituted compounds, while the remaining compounds stimulated the IgG production to a similar extent. Plots of the lipophilicity of the para-substituted compounds against their ability to induce PLN weight and cell gain showed a fair correlation, but induction of antibody formation tended to be counteracted at too high lipophilicity. No correlation between pharmacologic and immunologic activity of the compounds could be found. Data indicate that lipophilicity grossly favours PLN enlargement, but the divergent responses to the equilipophilic 3- and 4-brominated compounds, suggest conformational restraints as well.(ABSTRACT TRUNCATED AT 250 WORDS) | High | [
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// tslint:disable:member-ordering import { Component, Input, AfterContentInit, AfterViewInit, ChangeDetectorRef, OnChanges, SimpleChanges, OnDestroy, ViewChild, ElementRef } from '@angular/core'; declare class ResizeObserver { constructor(callback: ResizeObserverCallback); disconnect(): void; observe(target: Element): void; unobserve(target: Element): void; } type ResizeObserverCallback = (entries: ReadonlyArray<ResizeObserverEntry>) => void; interface ResizeObserverEntry { readonly target: Element; readonly contentRect: DOMRectReadOnly; } @Component({ selector: 'lib-primitive-numeric-slider', templateUrl: './template.html', styleUrls: ['./styles.less'] }) export class SliderNumericComponent implements AfterContentInit, OnChanges, AfterViewInit, OnDestroy { @ViewChild('line', {static: false}) private _lineElRef: ElementRef; public _ng_value: number = 0; public _ng_min: number = 0; public _ng_max: number = 0; @Input() public value: number = 0; @Input() public min: number = 0; @Input() public max: number = 100; @Input() public step: number = 1; @Input() public onChange: (value: string | number, event?: KeyboardEvent) => any = () => void 0; private _x: number | undefined; private _width: number = 1; private _destroyed: boolean = false; private _resizeObserver: ResizeObserver; constructor(private _cdRef: ChangeDetectorRef) { this._onMouseMove = this._onMouseMove.bind(this); this._onMouseUp = this._onMouseUp.bind(this); window.addEventListener('mousemove', this._onMouseMove); window.addEventListener('mouseup', this._onMouseUp); this._resizeObserver = new ResizeObserver(this._onResize.bind(this)); } public ngOnDestroy() { window.removeEventListener('mousemove', this._onMouseMove); window.removeEventListener('mouseup', this._onMouseUp); this._resizeObserver.disconnect(); this._destroyed = true; } public ngAfterContentInit() { if (typeof this.value !== 'number') { return; } this._ng_value = this.value; this._ng_min = this.min; this._ng_max = this.max; this._forceUpadte(); } public ngAfterViewInit() { if (this._lineElRef === undefined) { return; } this._resizeObserver.observe(this._lineElRef.nativeElement); this._resize(); } public ngOnChanges(changes: SimpleChanges) { if (changes.value !== undefined) { this.value = changes.value.currentValue; this._ng_value = this.value; } if (changes.min !== undefined) { this.min = changes.min.currentValue; } if (changes.max !== undefined) { this.max = changes.max.currentValue; } this._forceUpadte(); } public drop() { this._ng_value = this.min; } public refresh() { this._onChange(); } public setValue(value: number, silence: boolean = false) { this._ng_value = value; if (silence) { this._forceUpadte(); } else { this._onChange(); } } public getValue(): string | number { return this._ng_value; } public _ng_getCursorLeft(): string { const steps: number = (this._ng_max - this._ng_min) / this.step; const stepPx: number = this._width / steps; const left: number = (this._ng_value / this.step) - (this._ng_min === 0 ? 0 : 1); const offset: number = left * stepPx; return offset + 'px'; } public _ng_onMouseDown(event: MouseEvent) { this._resize(); this._x = event.x; } private _onMouseMove(event: MouseEvent) { if (this._x === undefined) { return; } const offset: number = event.x - this._x; if (offset > 0 && this._ng_value === this._ng_max) { return; } if (offset < 0 && this._ng_value === this._ng_min) { return; } const steps: number = (this._ng_max - this._ng_min) / this.step; const stepPx: number = this._width / steps; const left: number = Math.round(this._ng_value / this.step) - (this._ng_min === 0 ? 0 : 1); const leftPx: number = stepPx * left; let leftPxUpdated: number = leftPx + offset; if (offset > 0) { leftPxUpdated += stepPx / 2; } else { leftPxUpdated -= stepPx / 2; } leftPxUpdated = leftPxUpdated < 0 ? 0 : leftPxUpdated; leftPxUpdated = leftPxUpdated > this._width ? this._width : leftPxUpdated; let leftUpdated: number = 0; if (offset > 0) { leftUpdated = Math.floor(leftPxUpdated / stepPx); } else { leftUpdated = Math.ceil(leftPxUpdated / stepPx); } if (leftUpdated === left) { return; } this._x = event.x; if (offset > 0) { this._x += stepPx / 2; } else { this._x -= stepPx / 2; } this._ng_value = this._ng_min + this.step * leftUpdated; if (this._ng_value - Math.floor(this._ng_value) !== 0) { this._ng_value = parseFloat(this._ng_value.toFixed(2)); } this._onChange(); } private _onMouseUp(event: MouseEvent) { if (this._x === undefined) { return; } this._x = undefined; } private _onChange() { this.onChange(this._ng_value, undefined); this._forceUpadte(); } private _onResize(entries: ResizeObserverEntry[]) { if (entries.length === 0) { return; } this._resize(entries[0].contentRect.width); this._forceUpadte(); } private _resize(width?: number) { if (width !== undefined) { this._width = width; return; } if (this._lineElRef === undefined) { return; } const size: ClientRect = (this._lineElRef.nativeElement as HTMLElement).getBoundingClientRect(); this._width = size.width; } private _forceUpadte() { if (this._destroyed) { return; } this._cdRef.detectChanges(); } } | Mid | [
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My Most Important Job A few days ago, I went to my 10-year-old daughter's band concert. It was a great evening, and after the show a few parents told me they were surprised I'd made it, considering my schedule -- which got me thinking. To me, it was unfathomable that I could have something more important to do. This was my child -- I was supposed to be there. There was nothing more important I could do than be supportive as a dad. Somewhere during the course of our national dialogue, our expectations for parents have lowered, particularly for fathers. Today, I want to challenge every father to step up. If we want strong schools and strong communities, we need more dads involved. Young people know how important it is for dads to be involved in their lives. As I travel the country and talk with students, some of them tell me that their lives would be totally different if their father was around. The statistics on this front are staggering. Almost 24 million children -- one in three -- are likely growing up without their father involved in their lives. Those statistics are even higher if you look at the numbers inside our communities of color. That absence puts much too great a burden on our strong moms and teachers. Everyone is trying to do their part, but when dad is not around, we are all playing a man down on the team. We know that increasing parent involvement, particularly the involvement of fathers, is key to improving schools and communities across the country. As we work to drive down drop-out rates and increase graduation and college completion rates, fathers have an important role to play. Research shows that children do better in school and are less likely to drop out when fathers are involved. Engaged parents can strengthen communities, mentor and tutor students, and demonstrate through their actions how much they value their children's education. Great teachers and principals make a huge difference, but they can't do it by themselves. At the Education Department, we are investing more in parental engagement. We are re-doubling our efforts -- and asking Congress to double the budget for parent engagement programs to about $280 million from about $135 million -- in order to get more dads and parents engaged. We're looking at programs that are already making a difference and scaling them up to help improve more communities. These efforts at the Department of Education are part of a larger project underway through the president's Fatherhood and Mentoring Initiative to help dads connect to their families and to raise awareness about responsible fatherhood. Through this Initiative, the president is lifting up positive examples of fathers and father figures in local communities. These "Fatherhood Heroes" are connecting with local, community-based institutions like barber shops through the Fatherhood Buzz Barbershop Tour to help fathers get the tools and information they need to participate in the lives of their families. As the president has said, "Fathers are our first teachers and coaches. They're our mentors and role models. They set examples of success and push us to succeed ourselves -- encouraging us when we're struggling; loving us even when we disappoint them; standing by us when no one else will. And when fathers are absent, when they abandon the responsibilities to their children, we know the damage that that does to our families." Fathers: we must be there for our kids. Instead of lowering expectations, let's raise them. | Mid | [
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The Future FreedomPop is a popular app that allows you to receive and make phone calls and text messages. This app is free to download on most phones, click here to check it out on Google Play. This is ideal for the people who are trying to save money and cut the cost of their current phone bill. The best part is there are no contracts and the app is hassle free. Recently, FreedomPop has offered users unlimited WiFi for the low price of five dollars! This makes it hard for inferior competitors to compete. They have over ten million hotspots throughout the United States. In the future they hope to have over 25 million hotspots available for their users. These hotspots and WiFi plans are great for customers who would like to connect to the internet but have no service on their phones. This means that you take your phone that you have abandoned and get WiFi service at various hotspots for five dollars a month. FreedomPop reviews are so popular because you can easy saves hundreds of dollars. It allows users to have free services for their entire lives. If a user decides to close their account then there are no fees if you decide to cancel at any time. When you create an account you will have a username and password as well as your own telephone number. FreedomPop can turn your tablet into a phone so that you may text or make outgoing calls. Another great thing is that you will never have any surprises on your bill. The free plan offers 200 minutes along with 500 text messages and 500 MB of data. You can pay to have unlimited WiFi or you can upgrade and have unlimited calls for a same fee. These fees are still cheaper than other competitors and will save you lots of money that you can surely spend on something else. The Republican’s big win on election day will have serious implications for President Obama in his efforts to achieve almost anything. With the Republican’s win in the Senate, now both houses are dominated by the Republican party. It is a well known fact that this congress has been the least productive in all of American history. The President can expect less effective appointments in his judicial nominations according to Brian Torchin’s analysis. As noted in the Washington Post, the US Court of Appeals now has 9 of the 13 courts with judges appointed by Democratic Presidents. This is a dramatic shift from the Bush Presidency where 12 of the 13 were appointed by Republican Presidents and reflected that conservative ideology. The US Court of Appeals has tremendous political impact on important issues such as abortion, the environment, gun control, the rights of the accused in criminal hearings, immigration, to name a few. These are the hottest political issues of today. Although the President has had difficulty in getting his judicial nominees approved in the past, moving forward will prove nearly impossible if the Republicans deem it so. They now have the power, rather than merely filibuster, to refuse to hold hearings altogether. In the event nominees are approved, they will likely be more conservative and less progressive than those appointed to date. More than likely, the do-nothing congress and the Senate Judiciary committee will choose to obstruct and bog down the appointment process in an effort to diminish Obama’s legacy. Autonomous, self-guided machines are on our streets, in our skies, and now, in our seas. The Navy is testing drone ships that will be configured to “swarm” potential hostile vessels if they approach warships too closely. The technology has been developed over the last decade and some elements originated with the Mars Rover spaceflight programs. Kits, which cost about $2,000, have been developed that can be installed on any small vessel. The kits have sensors and radar that are combined with advanced algorithms to plot routes and speed, as well as determining a course of action. The kits will be distributed out to fleet commanders within a year. A book by Jared Haftel about these is said to be on its way. This swarm technique will allow suspect boats to be surrounded, isolated and destroyed if necessary. In a recent demonstration, 13 small unmanned patrol boats escorted a warship and eight of them broke off together and swarmed a simulated enemy vessel. Check out this video demonstration of the machines and how they work: | Mid | [
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May 22, 2018 Damascus Is Secured, Daraa Is NextTue May 22, 2018 22:02 | Scotthttps://southfront.org/syrian-war-rep... Late on May 21, Russian air defense systems, allegedly a Pantsir-S short to medium range system, launched at least four missiles at ?unidentified? targets over the Khmeimim air base The ‘Save Viking Waterford Action Group’, have called on new Minister for the Environment, Dick Roche, to make a commitment to the full excavation of the entire Woodstown Viking Site one of his first announcements in his new role. The National Monuments Act 2004, drafted by the previous Minister, Martin Cullen, invests the Minister for the Environment with arbitrary authority over Ireland’s heritage. The new act abolishes the democratic checks and balances which previously existed, meaning that Dick Roche now has sole authority over the future of the Woodstown Viking Site and other sites of crucial archaeological importance around the country. Chair of the SVWAG, Dr. Catherine Swift in reaction to Mr. Roche’s appointment: “Mr. Roche can make an auspicious start to his new job if he orders the full excavation of the Woodstown site, a site which potentially is one the most important archaeological finds in Europe. The previous Minister had prevaricated and delayed this decision for months, so we are calling on Dick Roche to grasp the nettle immediately”. Dr Swift continued: “The National Museum, the Heritage Council, the NRA and academics and scholars from across Ireland and Europe have called for the full excavation of Woodstown. We do not understand why the delay is necessary. The sooner the site is excavated, the sooner the bypass can be built. The hesitation denotes a propensity to put short-term economic interests ahead of the long-term benefits which would accrue from the excavation. It appears that the use of Public Private Partnership in the construction of the road may be a factor. The new Minister must put our heritage ahead of the profits for a private company. RSS and atom feeds allow you to keep track of new comments on particular stories. You can input the URL's from these links into a rss reader and you will be informed whenever somebody posts a new comment. hide help Comments (1 of 1) One of the themes at the public meeting was that people wanted to learn more about Woodstown and Viking Waterford in general. The campaigners have therefore set up a lecture series - the first one being by Dr Colman Etchingham on Thursday 7th Oct at 8 in the Glanville Hotel, Waterford. He'll be talking about Waterford region and Vikings in the annals | Mid | [
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If this is your first visit, be sure to check out the FAQ by clicking the link above. You may have to register before you can post: click the register link above to proceed. To start viewing messages, select the forum that you want to visit from the selection below. Easy pass for me. The cover art is a little blah. I agree with MernRa that the cover CG is weak. Like Angel T said no POP but they put NA episodes inside. Give me a break. I like the Filmation soundtrack but I won't pay $100 for it. Definitive no....a nice set if you don't have any of the episodes. But most of us already do so I'm not sure how these will sell. Cool packaging and extras... but not sure it's worth getting it just for those... With that said, I'm thinking the Power-Con give-away might be a sword of Power originally intended for this set in a different color... The 20 fan favorite episodes of New Adventures? I don't recall a vote on that ever? And why not just the entire series? That would make a lot more sense. Oh well I am still getting it. The soundtrack alone will make it worth it. Hey Super7 I'm looking forward to what you do for Classics and I'm awaiting these figures! I am very interested in the pressed cd & bonus items with this set! As I already have the BCI collection, but don't think Mill Creek will be selling anything of the bonus items separate. Definitely a great deal for lobng time fans & especially new-comers. FYI: A lot of times Mill Creeks's "Best of 10" or "Best of 20" are just the 1st 10-20 episodes of the series in order (a few of there other "best of" sets are like this, & are not actually a best of by fan selection.) This could have been the ultimate collection but instead it is a massive fail in my view. Seriously, why not package in all the NA episodes instead of skimping with just 20? I know some people hate NA (personally I love it), but for this to me the ULTIMATE collection it has to include them all. Same goes with POP. It needed to have them all. This is just another half thought out mediocre collection in my view. The Grayskull-art on the box looks great in my opinion. Much better than 30th anniversary castle by Alvin Lee. Fantastic job Baena! Can't wait to see the final sculpted facade when Mill Creek is ready to show it. This place-holder artwork is great in the mean time. I have no idea if this is again one of those instances where She-Ra is being treated as different license from the company's eyes (as past DVD-releases have proven), and that being the reason why no POP in there. Very curious about the TOP20 episodes of New Adventures. Wow, I'm very impressed by this. I hope it gets an international release. I have all the Filmation episodes, but I never watched NA and we can't get the MYP cartoon on dvd over here, so this, for me, is going to be as good as it gets ...and hopefully She-Ra will get better treatment when it's her 30th. That is the only snag in this boxset for me. While I agree that ideally She-Ra should have been included (IMO more deservingly so than NA.... they could have left NA out entirely and simply doing that would actually make this set more definitive IMO... though I do admit that it does seem odd that they didn't just include 4 more discs with the rest of the NA series since they were including it at all), She-Ra is considered a completely separate license and the DVDs of the show are currently being released by Classic Media while He-Man is being released by Mill Creek. The licenses are split between two different distributors (if I understand things correctly, Classic Media owns both overall properties, but I'm guessing that for all intensive purposes the DVD division of Classic Media is a separate entity from division that owns the Filmation properties outright and they in essence licensed She-Ra to their DVD division while licensing He-Man to Mill Creek). Still, it would be nice if She-Ra at least had some presence in this set. If nothing else it would have been nice if they could have "fudged" around the license issue and included SOTS and maybe the Christmas Special, especially since we haven't gotten an actual release of SOTS under Mill Creek or Classic Media so far. But at the same time, I'm kind of glad that this set doesn't include more than it already does in terms of DVDs that I already have. I already have the complete series of Filmation MOTU, and MYP MOTU a couple/few times over between the various BCI and Mill Creek releases (including multiple BCI purchases for MYP to get various exclusives, and various best of and volume/budget releases), and the complete NA series from BCI. The same goes with She-Ra between the BCI and Classic Media releases (all of the BCI season sets, the best of, the convention/he-man.org exclusive alternate packaging for the best of, the single disc SOTS, and the Classic Media Season 1 Part 1 and Complete Series releases). In all honesty I would almost be happy if they just included the top 20 episodes from the three series that are included and called it a day. While most people probably haven't gone as crazy collecting the various DVD releases as I have, between all of these releases its likely that most MOTU fans already have all of these series (or at least the ones that they want and care about most) on DVD in some form or another. This is essentially a repurchase to get the new packaging and extras. So anything that helps reduce the cost-to-redundant-purchase ratio is just fine in my book (i.e. the lack of She-Ra's inclusion). Originally Posted by Dr Kain Wait, the math is not right. How is 130 + 65 + 39 189 episodes? The press release says that only 20 episodes of NA are included. Pay attention. - - - Updated - - - Originally Posted by JafariStew FYI: A lot of times Mill Creeks's "Best of 10" or "Best of 20" are just the 1st 10-20 episodes of the series in order (a few of there other "best of" sets are like this, & are not actually a best of by fan selection.) Yeah, but I wonder if that's how they will handle NA. The reason those other "best of" releases are just the first 10-20 episodes is because they are literally the same discs from the larger season sets with different artwork on the disc and packaging. It's just a cheap repackaging of discs that they've already authored. Since to date Mill Creek hasn't released NA in any capacity prior to this upcoming set, it is at least a little more likely that it's not just the first 20 episodes in order. I was really considering this for the neat looking box, the Eternian gold sword and the soundtrack although I already own the entire Filmation MOTU series and the entire MYP, but since there is no POP and NA is incomplete I will probably pass.... | Low | [
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BERKELEY — The former Hotel Durant will reopen in April as Graduate Berkeley, the latest piece of “transformative real estate” in the “one-of-a-kind portfolio of timeless assets” of self-described counterculture investors AJ Capital Partners. The 143-room landmark hotel originally opened in 1928 and was named for UC Berkeley founder Henry Durant. Included in the renovation is the hotel restaurant, Henry’s, “a game day watering hole and neighborhood staple for Golden Bear fans and hotel guests,” according to a news release from the hotel’s publicist, Meg Connolly Communications. “A nod to Berkeley’s hometown pride, Henry’s will maintain a menu of honest American classics with the addition of a few comforting favorites including Sloppy Joes, crispy chicken sandwiches and skillet cookies,” the publicist promises. Graduate Berkeley will also feature a boardroom and event space for large groups and events such as business meetings and social gatherings. The hotel is a block south of the UC Berkeley campus. The opening is slated for mid-April but no specific date was set as of this week. Graduate Berkeley and another Graduate Hotel slated to open this spring in Lincoln, Nebraska, will be the latest in a “well-curated, thoughtfully crafted collection of hotels that reside in the most dynamic, university-anchored cities across the country,” according to the publicist. Other Graduate Hotels are in Ann Arbor, Michigan; Athens, Georgia; Charlottesville, Virginia; Madison, Wisconsin; Oxford, Mississippi; and Tempe, Arizona. Additional Graduate hotels are slated to open in Minneapolis, Minnesota and Richmond, Virginia this year; in Bloomington, Indiana and Seattle, Washington next year; and on New York City’s Roosevelt Island in 2019. Chicago-based AJ Capital Partners — “AJ” stands for “Adventurous Journeys” — launched the Graduate Hotels brand in fall 2014. The company also owns and operates properties elsewhere in the United States and on the Caribbean island of Anguilla, according to its website. | Low | [
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VB: Huskers hit past Mavericks to cap Omaha trip with sweep Husker Annika Albrecht had a match-high 15 kills and a .375 hitting percentage. 3 0 26-24, 25-15, 25-13 Husker Leaders Kills Albrecht – 15 Blocks Stivrins – 4 Digs Maloney – 14 Attn: 5351 Story by Pat Radigan Corn Fed Sports Nebraska overcomes shaky start to sweep past Mavericks The Nebraska volleyball team got back on track with a sweep of Omaha in front 5,351 fans at Baxter Arena on Saturday night in Omaha. A slow start for the Huskers made the first set interesting, but Nebraska turned things around in time to fight off a set point and hang on for a 26-24 win in the first set. After being knocked off by unranked UNI to open the day, Nebraska erased any hope of another upset with easy wins in the next two sets to finish the Omaha Challenge with a 2-1 record. Annika Albrecht led the Husker charge with 15 kills and 8 digs as part of a .327 hitting performace for NU as a team. That number came despite eight hitting errors and a .159 mark in the first set. After surviving the set, though, Nebraska committed just five errors the rest of the match and hit .450 over the final two sets. Freshmen Lauren Stivrins and Jazz Sweet were also key components to Nebraska’s efficient attack, adding seven kills apiece, while each committed just one error. Briana Holman was second for Nebraska with eight kills, but left the match in the third set after injuring her ankle. Her spill brought an eerie silence to the arena, before she eventually limped off with help from teammates. Holman’s injury brought freshman Chesney McClellan into action for the first time this season. Omaha had a chance to take control of the match early, but Nebraska won five of the final six points of the set to come from behind and sneak out the set. The Mavericks took a 23-21 lead after a ball handling error on NU, but back to back Omaha errors evened the set. A questionable four-hit call against Nebraska gave UNO a set point opportunity, but Mikaela Focke erased it with a kill. Another Maverick error gave NU its first set point, and Albrecht put it away to give the Huskers an early edge. Nebraska’s offensive efficiency made the next two sets much more comfortable, and Omaha managed just 10 kills in each set as the Huskers errors diminished and made it hard for the Mavericks to run points. The win technically gave Nebraska the tournament title via tiebreaker, as the only team to sweep the Mavericks, and makes it seven sweeps in eight matches for the Huskers. Now, Nebraska heads into conference play and a trip to take on No. 2 Penn State next Friday in University Park. The Digital Darkroom Follow on Facebook Corn Fed Sports was started as a student start-up, but has evolved into a new way of providing Husker sports coverage. The majority of our staff isn't devoted to just one or two sports, and we value coverage over 'analysis' where others struggle to see the difference. But most of all, we are devoted to providing quality coverage of ALL Husker sports, ALL the time as we try and change the game of how college sports are covered. | Mid | [
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Friday, May 20, 2011 AS EK ÉÉN WOORD GLIM, MOET EK ÁLMAL GLIM I realize you probably think I'm a 'conspiracy theorist'. I also realize you are probably not inclined to believe anything I say that smacks of a 'conspiracy theory'. Very well. What we should all be able to agree upon is that it is vital for a free man (or woman) to be capable of critical thinking. What is 'critical thinking'? First, an example of what it is not: Critical Thinking is not turning on the television, hearing a story, and saying "Hallelujah! I've heard the truth!" For a real life example from recent news, let’s take the story about Osama bin Laden's death. Despite the fact that I have been saying the man is dead for years, it is now 'ok' and within the public perception of 'normal' to say "I believe the man is dead." Why? Because anyone did any investigating or research into the life and death of Osama bin Laden? Because you or someone you know physically touched his lifeless corpse? No. Because the TV told you. A healthy amount of skepticism demands some sort of evidence, some sort of proof. Citing a news source does not equal proof. Saying 'because Fox News said so' doesn't make it any more true than if I said 'because Alex Jones said so'. It's not just that people believe it, it's alarming how EASILY they believe it. This opinion went from 'only kooks say he's dead' to 'everyone knows he's dead' in the span of 1 hour. Just *poof* the tv said it, so it's true. There is no journalism going on. There is nobody asking a hard question. This is a White House press release being passed to the American people from all directions, by all news sources, completely unaltered and without investigation -- literally, government propaganda -- from an administration that some 60% of the populace claim to dislike. So why does the TV's magic 'say-so' verify the truth of this propaganda without question for so many? The implications of this are both astounding and frightening. The hard questions need to be asked. The difference between 'propaganda' and 'journalism' is the necessary process of close scrutiny of bold claims. Reading a press release verbatim is not journalism. To believe such 'news' requires implicit faith in the source (in this case, the Obama administration.) I do not have such faith. I do not relish the thought of being portrayed as a 'conspiracy theorist' for insisting on such old-fashioned standards, but if that's the label I get slapped with, so be it. But, I said this was about Critical Thinking, and so it is. If we want to 'think critically', how can we analyze this news, or all news? I have devised a sort of test. Since 9/11 we have been subjected to a whole new world of government oversight. We have had the Patriot Act, the Department of Homeland Security, and the TSA arise out of nowhere to become agents of Big Government in places where previously there were none. This has all been done, according to the official story, 'to protect us from terrorists'. There is always a danger of terrorism. Somebody will always dislike the US. Are we supposed to believe then that our Founding Fathers got 'Freedom' wrong, and what they should have said was 'the government takes care of everyone. The government monitors everyone. The government watches, arrests, prosecutes, and executes. The government cannot be questioned.' Is the breast-groping, child-molesting, nude-scanning TSA what freedom is all about? Or is it a 'necessary evil' to keep us safe from terrorism? If it's simply a 'necessary evil' then I pose the question 'For how much longer?' We have wiped out 2 countries, staged revolutions in foreign nations, killed 2 million people, and now by all counts Bin Laden is dead. So if all these things are temporary measures, then I challenge the government to fire Janet Napolitano, dismantle DHS, abolish the TSA, and let the Patriot Act expire. If your version of history is true, then the war is over. We won. So the wartime measures need to be done away with. If my version of history is true, then don't do any of these things. Continue to harp on the threat that is terrorism, and insist that we need to be monitored and frisked and groped for the foreseeable future. (For our protection, of course.) In the end, this is the true measure of motivation. If the true motivation is as benevolent as they would have us believe, when does it end? It didn't end with the ousting of the Taliban. It didn't end with the fall of Baghdad or the execution of Saddam. If it doesn't end with the death of Osama bin Laden, then everything I've said about the true purpose of the "War on Terror" is vindicated: It is an intentionally perpetuated war used as a catalyst to seize power. If it does end, here and now, with the death of Bin Laden, then it will prove that these measures were temporary and I will publically renounce every 'conspiracy theory' I ever endorsed. Because you see, I'm not a conspiracy theorist... I'm a critical thinker. I have no attachment to any particular 'theory' nor do I even want my allegations against the US government to be true. I would by far prefer to be wrong about these things. Unfortunately, the reality of life does not match the propaganda spewing forth from my television set. As an exercise in critical thinking, I would like everyone to begin questioning the TV. Who writes the news? Where does it come from? Why should I believe you over anyone else's version? What is your agenda for telling me these things? Begin to develop a broader scope of thought. If people questioned Fox and CNN's version of things with half the intensity they question mine, the world would be a better place already. | Mid | [
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If you look at historical planting data for soybeans in the US, the trends change dramatically after 1996 (see chart above). That makes sense because “Roundup Ready” herbicide tolerant soybeans were commercialized that year. Since 1999, the vast majority of soybean acres have been planted to this GMO trait and there are now about 20% more of them. These soybeans are very attractive to farmers because weed control is much easier and doesn’t involve the sort of plant injury that came with previous “selective herbicide” options. It makes it easier to farm “no-till” which conserves water and uses less fuel. But it wasn’t just soy planting that changed in 1996. More Corn Corn also became a GMO crop in 1996 with the launch of “Bt-Corn” which is resistant to the European Corn Borer, a serious pest in the Western Corn Belt. Farmers started planting more corn, particularly after 2003 , but the area gain was not as significant as with Soybeans. Glyphosate tolerant corn was added in 1998 and improved in 2003. The Price of Precaution But it wasn’t just the commercial GMO crops that saw a change. Spring wheat (used for high quality bread flour, pizzas etc) saw a dramatic loss of planting area, dropping a full 20% between 1995 and 1999. Much of this was switched to soybeans and later to corn. The spring wheat area has continued to decline and is now 40% below it’s peak. That might not have happened to this degree if two biotech traits were commercialized early in this century. Monsanto was developing a glyphosate herbicide tolerant wheat and Syngenta was developing wheat resistant to a disease call “Fusarium head blight.” These would certainly have helped keep spring wheat more attractive as an option for growers. But nervous customers in Europe and Japan put pressure on the North American wheat industry – threatening not to buy any North American wheat if any GMO wheat was commercialized. The wheat industry gave in and asked Monsanto and Syngenta to shelve their biotech wheat programs – something they now deeply regret. The wheat growers of the US, Canada and Australia have since agreed that they will do a simultaneous launch of any future biotech wheat so that the Europeans and Japanese cannot strong-arm them again. But any such advance has been delayed by 10 to 15 years. The GMO-pact countries are the producers of most of the wheat that goes to countries that can’t produce enough for their own needs (which includes Europe and Japan, but also the Middle East and many other areas rich and poor). Considering how global wheat production is failing to increase as rapidly as global demand, the “Precaution” leveraged by rich Europeans and Japanese has insured that this “Staff of Life” will become very expensive for the world’s poor. There Are More Forces at Work Than Technology In the “Pre-biotech Era” soybean prices were rising at a modest rate which didn’t keep up with inflation. The graph above shows that between 1995 and 1999 the price growers got paid for soybeans crashed by almost 40%! But then a new trend started where prices were rising at ~10% per year. Actually this same price trend has occurred for all the major and minor crops (corn, spring wheat, winter wheat, durum wheat, barley, silage corn….). This can’t be explained by the introduction of GMO crops alone, although the drop could be related to the delays in regulatory approvals in Europe that disrupted trade. This cross-crop phenomenon is probably driven by the “Freedom to Farm Act” of 1996, passed by Congress. It wasn’t really an end to government interference in these markets, but it was a change in the way the government distorted the market via farm policy. This complicates the analysis of US row cropping trends. They are driven by a complex mix of biotechnology, increased private investment in the breeding of some crops and not others, ethanol “blender credits” and tariffs, and the effects of grain subsidies. Many people assert that the US has a “Cheap Food Policy,” but if that is what was intended, it is clearly not working! Oh, by the way, the grower’s are not getting rich on this new trend. These commodity price increases end up driving up land rents so the money is flowing to the land owners (former farming families and land speculators.) Since the introduction of biotechnology, the rate of yield gain for corn has increased by a factor greater than two. Some of this is from the traits themselves, but it also involves the more sophisticated seed treatments that are now applied to the very valuable seed and the increased investment in breeding (e.g. Marker Assisted Breeding). In years like this with high commodity prices (e.g. as in 2007/8) farmers will also apply fungicide and/or insecticide sprays that are now easy to “pencil” adding several more bushels to their yield. Opponents of GMO crops mistakenly linked the increased chemical use in 2007/8 to biotechnology when it was simply a function of economics. The soybean yield trend shows a “lag” after the introduction of biotech and then a similar but slightly slower rate of gain. This is mostly because of the expansion to areas that were not traditionally major soy producing sites and the lower yields of those regions due to colder temperatures (Northern expansion in Minnesota and North Dakota) and lower rainfall (Expansion to the West). Spring wheat yields are always highly variable because it is mostly planted in more marginal land, but there has been a distinct acceleration of yield gain for this “orphan crop” that didn’t get to be improved by biotechnology. What has happened is the farmers have “intensified” their production of the spring wheat that is still grown. This involves using “certified seed” grown specifically for that purpose rather than just “saved seed” out of their last grain harvest. It involves a “split application” of fertilizer, better seed treatments and possibly a fungicide spray. This represents a greater financial risk for the farmer, but also a greater reward when things go well. These are the kind of adjustments that farmers can make which provide encouragement that the looming global food crisis can be at least partially ameliorated. So, by any measure 1996 was a watershed year for US agriculture. Agriculture is a remarkably dynamic and adaptive industry based on the independent decisions of thousands of individual family business owners who grow our food. The notion that this vast network is “controlled” by any business or government is absurd. Graphs based on USDA, National Agricultural Statistics Service data. You are invited to comment here or to write me at [email protected]. I would be happy to email a copy of these and other slides or you can download them from SCRIBD. My Website is Applied Mythology. About the Author Steve Savage Born in Denver, now living near San Diego. Agricultural scientist for 30+ years with a Ph.D. in Plant Pathology. Have worked for Colorado State University, DuPont and Mycogen and for the last 13 years consulting for all sorts or companies, universities and grower groups. Experience in biological control, natural products, synthetic chemicals, genetics, GMOs and agronomic practices. Have given multiple invited talks on the interaction between agriculture and climate change (both ways) Knowing that you come at these issues from “How do we feed 6-9 billion people sustainably?” has definitely forced me to think about my own assumptions regarding agriculture and food production… I appreciate that. Still struggling with the GMO issue, though… I get it at many levels, though still wonder about potential impacts of their introduction into the broader ecosystem (because genetic material doesn’t respect property boundaries… this also ties into some of the intellectual property issues that have arisen), and, of course, the human health issue. I’m sure you already know about the data review recently released on organ disruption in animals and GMOs. I looked over the introductory section of the study, and see that the main conclusion the authors present is, essentially, more study is needed (with longer time frames). I’m interested in seeing your response to this (maybe that’s another post as opposed to a comment response). I don’t know enough either way to make any bold pronouncements… I would be interested in your thoughts, though. Jeff, This is definitely about how do we feed the global population and what we see with wheat (denied the benefits of biotech but still innovating by other means) is very encouraging. If the organ disruption thing you are talking about is what I think it is, it is a classic example of “junk science” and/or “agenda science.” Can you send me a link to what you mean? I think I blogged about this a while back. We have already had one Green Revolution to stave off worldwide famine, which resulted in dependence on petro-based chemicals and led to the megalithic power of ag corporations…as well as GMOs. That really concerns me, whatever benefits might have been gained. I would much rather find ways to make local populations self-sustaining and give them the resources, and knowledge, to produce the right amounts of food for their area through methods that are appropriate for their area. If we continue to have developed (Western) countries developing all technologies and producing most of the food, that will only continue an aid-culture and leave people helpless on their own. There are a lot of good efforts underway to make region and scale-appropriate advances for food production in the developing world. Governments have pretty much abandoned those investments but fortunately groups like Gates are filling the gap. I just spoke with a colleague who spent two years in India helping an Indian owned company (grandson of a Ghandi inner circle figure). They run an integrated bio-refinery and have >15,000 small local farmers who supply sugar cane all coordinated via cell phone. The farmers then plant corn and other food crops during the rattoon. The company offers small cap loans for fertilizers etc and they are teaching the farmers to build the organic matter in their soils. They definitely use some modern technology but in a very small scale way. They supply all their own energy and sell various high value fermentation co-streams to bring wealth into the community. Appropriate ag in the developing world does not need to be primitive. Thanks, Steve, and of course not. But the question is what aspects of modern “technology” will be used or accepted? If that development assistance comes with a push for chemicals, monocultures, and other typical industrialized methods, then we may just be creating more problems for the world down the road. I saw a film recently that highlighted a gardening/farming initiative in India. The people explained how the chemicals that were originally used only hardened the soil. But when a sustainability-focused organization started to help them and taught them how to use organic compost, they were able to regenerate the soil and avoid using pesticides. JUSTIN, People seem to think that no one in agriculture learned anything about how to do things better since the 1960s. In fact tons of things have changed. As for the Organic compost, as I’ve written many times it has a big Carbon Footprint issue because on a commercial scale there are always enough methane emissions from “aerobic” composting to make synthetic nitrogen look great by comparison. Steve, I do not mean to be obtuse, but I really am not seeing much other than how to maximize benefits to humans through agriculture. I am still left asking, How are monocultures, pesticides, GMOs, agribusiness monopolies, factory farms, and animal gene/morphology alteration, to name a few, good for the planet and *other* beings that live upon it? Let me be clear: I am not saying we should sacrifice humans and should do what we can to provide adequate food (and other resources) to everyone, justly. But I feel it incumbent on us to make sustainability as high a priority as production. Justin, When one steps back and looks at all the trends in Ag, particularly since the 1980s, they go in the right direction for sustainability. US fertilizer use has not increased even though productivity has increased dramatically. The average toxicity of the pesticides used has dropped with the vast majority falling in the EPA category IV and only 0.2% in California in the category I which most people imagine when they hear the word pesticide. GMO’s have been declared safe by every national and international panel of scientists that have reviewed them. There are no monopolies in ag. There are some consolidated segments like grain trading and seeds, but those are still much less concentrated than something like computer chip manufacturing or grocery retail. The vast majority of US farms are still family farms – its very well documented and I’ve visited scores of them and they are in no way “factory-like.” The World Wildlife Fund agrees that the best way to protect the other biota of the earth is to be extremely productive on the land we farm so we don’t have to convert more natural land to farming. Moving to something like Organic has the opposite effect. I would like to see even more good practices adopted in ag, but the main limitation to that is the short-term income demands of the mostly city dwelling people who own the majority of farmland. The standard structure of farmland leases works against making the optimal investment in building soil quality – something that takes years to pay off fully. So reciting all the demonizing language about farmers accomplishes nothing for the planet. Help me find the greedy, ignorant land owners and convince them to make a long-term investment in their asset. Hmm. Those are interesting points. Maybe it is just my ignorance, or predisposition, but millions of acres devoted solely to corn, soy, wheat, or even almonds, or the muscles flexed by Monsanto and Cargill, or the billions of animals raised in confined enclosures and processed with lax regulation and oversight…there is a lot I still see that disturbs me, whatever the trends might be. Also, I am not trying to demonize farmers. I have great respect for farmers, especially now that I work with and represent them every day via the Farmers Market here. I am just as concerned as you are about supporting them; I just also want to be sure that we are not doing so at the expense of other things. Justin, There are real limits to the muscles of Monsanto or Cargill. Cargill is in an extremely low magin business with very real competitors like Bunge and Continental Grain and ADM. These players all have huge leverage vs the farmers, but they are in intense competition with each other. I would never want to be in that business, but its something that has to be done and scale is critical to survival. Monsanto has muscle based on its ownership of the foundation seed companies that develop the new inbreds for hybrid corn etc. They still have significant competition from DuPont (Pioneer) and Syngenta and some small companies. As for the CAFOs, there are alternatives that could work for something on the order of $50/cow if we could establish an ethical meat category that was scientifically based. The problem is that the “band width” for ethical purchases is all tied up with Organic which is not the most efficient or rational solution Marc Ballat Steve, “The average toxicity of the pesticides used has dropped with the vast majority falling in the EPA category IV and only 0.2% in California in the category I which most people imagine when they hear the word pesticide. GMO’s have been declared safe by every national and international panel of scientists that have reviewed them.” IMHO, it is a fact in recent history that the homologation of a number of new substances used in agriculture has been too quick. As you often point out, many substances allowed in the last 50 years have been banned or are being banned for their impact on animal and human health. Others have become useless due to resistance, which is not, in my understanding, compatible with sustainability. Saying today that ‘this is safe according to scientists’ ignores recent history and ignores the fact that studies conducted to obtain homologation of a substance or GMO are made by the company itself ! Take a deep breath and read again. Studies supporting the homologation of a new substance or seed are conducted by the company that has invested large sums of money in it. Take another deep breath and read the following. Those files are then reviewed by national administrations. In the US and in Europe, it has happened more than once that experts working for those administrations are, have been or will be working for private companies that request homologations from the very same agencies. That is a great guarantee of independency, isn’t it ? Once a product has been homologated in one country, it becomes much easier to obtain homologation in other countries. Prior to becoming an organic fruit farmer (I admit having a bias thus ;-), I worked 10 years in IT, out of which 4 in a European Safety Agency : whether food or aviation, the fact is that once something is homologated in one big country (and the US count among those) it becomes very difficult to reject it in another one (e.g. the EU). Otherwise, the latter becomes subject to commercial retaliation from the other : ‘you don’t eat my GMO’s, ok, we won’t eat your stinking cheese any more’… Monsanto long claimed that glyphosate was harmless whereas it is now under scrutiny from the EPA after argentinians scientists published a study in which they say it is carcinogenic. At the same time, it is reported that weeds are becoming tolerant or resistant to glyphosate. Bt corn could be another time-bomb. Although Bt is used in conventional and organic agriculture, its use is limited in time (a few applications a year), in quantity and only concerns the aerial part of the plant. In Bt corn, it is present in the roots also and it has been found that the concentration of the ‘Bt gene’ has increased a lot in waterways close to Bt corn fields where it could be harmful to marine life. From a sutainability point-of-view, corn requires a lot of water during summer. Even if it seems undisputable that round-up ready soybean and Bt corn have helped farmers increasing yields, only time will tell if those yields can be maintained in the future and with exactly what environmental impact. Steve, I completely understand–there are very real pressures to produce more food, more quickly, more cheaply, and so in those moments ethics and ideals get pushed to the wall. However, I am going to keep pushing back. We have to take ethical considerations into account, to think about larger sustainability questions and the future generations, instead of myopically focusing on the bottom line right at our toes. Marc Ballat As if my previous post wasn’t long enough, I’d like to add one point that strikes me after selfishly re-reading myself. We should re-think the way inventions are fostered and protected : – a patent is limited to 20 years – shareholders want ROI as high and as quick as possible. Reflecting upon your comments on the land owners, I come to the conclusion that the same applies to the greedy share owners. Marc, It can cost a company 200 million dollars to do all the research required by regulators to register a new chemical. No government is going to pay for that and the logic is that the company that can benefit from the sales must pay it. If you have some other approach I’d be interested to see what it is. Even though the company pays for the testing there are very detailed rules about how it must be done and how the data is reported. It becomes impossible to hide negative results. Yes, many old pesticides have been banned, almost all being things that came into use before we had agencies like EPA. I can only think of one major new chemical that was banned because of an unexpected environmental issue, fipronil. As for patents, that is necessary to make it worth it for a company to invest all that money to invent new things. Again, there is no other source of money on that scale. Even Universities and government scientific discoveries tend to be patented because that gives companies incentives to license and develop commercial products. The patent system actually spurs further innovation because the rules require that the patent applicant “teach” enough detail so that others can read and understand the novel technology. That in turn tends to give people ideas for other novel inventions. People like to complain about all these things, but they are part of a well functioning Capitalist system. Unless you want to live in Albania or North Korea that is the way it is going to be. Even China has realized that these things are important. It is fine to do “open source” invention for fast-moving, low expense areas like software. I don’t think you can have industries like agricultural chemicals, seeds or pharmaceuticals without mechanisms to give anyone the incentive to invest hundreds of millions of dollars over 7-10 years before ever selling a product. Without protection no one in their right mind would do it. Marc, One last point. The reason that we have been able to ban the use of the old, nasty, pre-EPA pesticides without losing progress on agricultural productivity (which helps save natural lands) is that the patents, regulatory process etc make it worth-while for companies to make the huge investment to find the new, safe, effective alternatives. It is also those same discovery engines that provide the leads for public health-related insect control – low value “bid markets” that would not be worth the investment unless it can “ride along” with agricultural chemical discovery. There are millions of poor people who are being protected from Malaria etc because of this. There are major groups working very hard to undermine this system, but they offer no other way to get the job done. When the climate gets to the point that companies stop doing this work, we are in serious trouble Marc Ballat Steve, I may have expressed myself in an unclear way but as you probably know, English is not my mother tongue. Let me try to re-phrase and explain. I criticize the patenting system and the shareholders in the agricultural domain in the same way you blame land owners for not fostering sustainable practices : a 20 year patent and impatient investors are not the adequate incentive. I do appreciate the need for an inventor to see his investment protected from being copied and I do respect private initiative (keep in mind I left the public sector to try and become a farmer). However, they were never designed to guarantee public health and environmental sustainability. This is a new challenge for mankind and we need to think fast how to address that issue. I do not criticize the fact that a company pays for the registration of a substance or seed but the fact that the study is carried-out by the company itself, not by an independant laboratory. And in my experience, those who have to review the files are either not competent enough or not independent enough (ok this is a very, very rough judgment based on my own limited experience). However, we have enough examples of an industry that has falsified reports and a regulatory body that hasn’t done its job (AIDS infected blood in France, nuclear industry in Japan, Mediator medication in France) to realize that the system has flaws. All democratic, capitalist countries. Communism in eastern Europe has probably harmed the environment more than capitalism in the west and even though it could be an interesting experience from a curiosity point-of-view, I do not wish to live in a communist country. Would be complicated too : except North Korea (Albania has joined the NATO in 2009 and though plagued with corruption, it is no longer considered as a communist country), I do not see any other example left. The fact that communism has failed to last longer than liberal capitalism does not prove that the latter is sustainable. It may simply prove that capitalism is more efficient at producing with less resources. Economically more sustainable but not environmentally. Marc, It is interesting. For my college application to Stanford in 1973 the essay question was, “If you were to write a book, what would it be about.” I said a comparison of the environmental record of Capitalism and Communism. I think that there are ways that a country like China can just arbitrarily decide to do a good thing (e.g. build huge wind farms) as much as they can decide to do a bad thing (like build coal plants at a frenetic pace). Here in the US we have lawsuits for decades that block the building of the wind farm, but then we had a clean air act that stopped acid rain to the point that farmers are starting to have to apply sulfur. We probably don’t disagree as much as it may seem, but come at the same goal differently. Thanks for participating in the discussion. Recycle Creative Commons All posts on Sustainablog are licensed under the Creative Commons Attribution-Share Alike 3.0 license. You are free to reuse and remix our content provided you link back to the original post, and offer your new work under a similar license. Please note that some elements of posts (images, videos) may come with different licensing terms. | High | [
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ABOUT THE CONTENTS OF THIS TRANSCRIPT: This telepathic channeling has been taken from transcriptions of the weekly study and meditation meetings of the Rock Creek Research & Development Laboratories and L/L Research. It is offered in the hope that it may be useful to you. As the Confederation entities always make a point of saying, please use your discrimination and judgment in assessing this material. If something rings true to you, fine. If something does not resonate, please leave it behind, for neither we nor those of the Confederation would wish to be a stumbling block for any. CAVEAT: This transcript is being published by L/L Research in a not yet final form. It has, however, been edited and any obvious errors have been corrected. When it is in a final form, this caveat will be removed. Sunday Meditation November 18, 1990 Group question: The question this evening has to do with how individuals and groups, or any people that are in relationship with others, can work through the blockages that seem to get in the way of sharing as fully as possible the feeling of love, with ourselves, with each other, and with the group. How can we remove those patterns of thinking and behaving that tend to drain away, or even keep us from seeing the feeling of love and compassion for others? (Carla channeling) I am Q’uo. Greetings to each of you in the love and in the light of the one infinite Creator. We thank you most humbly for allowing us to share in your meditation and for calling upon our people to offer what information it is within our grasp to offer. By this we mean to imply that we are not without error ourselves, for we are brothers and sisters along the infinite path. We have had your experience, and you do not think that you have had ours. That is an artifact of your perceptions of time. Time, space and all that dwells in those areas are illusions. Not relative illusions, but absolute illusions. Were one to be able to see with the eyes that pierce flesh and see spirit, we would see beings of light surrounded in a matrix of energy vortices. Each of you is an unique being, yet one with all that there is. It is when one finds paradoxes such as this one that one realizes most clearly that one is treading on fruitful metaphysical ground, for paradox and mystery are the signs of the infinite One. You wish this evening to know more about the alteration of behaviors in order to operate affirmatively and positively. We would ask you to move one step backward with us, for it is not your behavior, but your being, your consciousness, your inner choices, that dictate with a ruthless certainty that which you shall perceive and notice, as you are not within the density you enjoy aware that the illusion is so complete it is easy to identify consciousness with behaviors, and gaze at the behaviors instead of finding the root of those behaviors. Now we have said to you before that the biocomputer which is your conscious mind is designed to make choices. In reality, your consciousness has the very basis of the illusion, that is, thesis and antithesis. So let us turn our gaze inward, and realize that our biocomputers have been programmed for this incarnation on a continuing basis; however, as it is popularly suspected … (Pause) I am Q’uo, and greet you once again in love and light. This instrument was much distracted because it required a liquid. We shall proceed. Those decisions made early in the incarnation when one was quite behind hand in grasping the larger truths concerning the great difficulties those you know as parents experienced. You were therefore victimized by whatever patterns of their negative influence were at that time present or at any other previous place in your flow of time present; further, much of the popular culture of your people given as the absolute understanding of “they,” as in “they say,” “they think,” you have purchased, without reading the ingredients, metaphysical food that you may find giving you a metaphysical stomachache. The most common legacy of the childhood in your culture is low levels of admiration and love, nurturing and forgiveness of the self. The entire world of personalities you may well be willing to forgive; but you yourself are often dazed by such excellent [conditioning] that there is no way to please the self, each having internalized in its own way the negatives of parental disapproval and lack of understanding, verbal and physical abuse, often in subtle ways, that you have experienced. Once these patterns have been set up, and this occurs quite early in life, usually, the rest of the incarnation is spent upon an arena which has been constructed to challenge you with these seeming self-destructive and limiting programs within the biocomputer. After these biases are in place, more and more the entity will notice and be aware of those things which are relevant to its self-destructive concerns. We ask you to allow the inner feeling of self to become crystallized at this time, and we shall pause. (Pause) Do you see the treasure that lies within you? Which do you think is reality? Which do you think is illusion? The first step towards altering one’s state of consciousness is the honest and actual realization that you are not that which begins and ends in this incarnation or within this illusion. This begins to distance the self, that is, the consciousness, from that beloved animal of second density which sacrifices a great deal to carry you about. It is well to be a careful and generous steward to your own physical vehicle; however, it is your ally and your friend, rather than yourself. When you have clearly made that distinction, you may begin to see the absolute subjectivity of perception, which is your own. The environment gives you a thousand messages, a hundred thousand, a million, so quickly, so very quickly, and the computer chooses that which it will notice, that which it will perceive. However, most are not aware that they have, at some point in the past, chosen to program the computer in such a way as to offer detuning, depolarizing and the heaviness of blocked lower energies. Instead of feeling helpless, instead of watching your behavior that you may behave correctly, take thought of your spirit and realize that all choices that have been instrumental in creating existing programs are your own. Listen. Can you hear the sounds of the household? Were you aware of them before we asked? Feel the slight breeze that drifts languidly in warm air currents across your skin. How many millions of receptors there are. Think of all that you have seen as you came into this environment, this domicile, and met those in the circle of one, some for the first time. How much of that which you saw did you perceive? Perhaps two or three percent at the most, for the computer cannot carry the full sensory stimulation and create aught but chaos. Thus, choices are made which enhance, or seemed at one time to enhance, one’s ability to survive, to cope, and to behave. That which has been programmed can be reprogrammed. Now we do not speak as if the Creator has nothing to do with this process. However, we believe that it is the will, passionate and joyful and complete, of the seeker to become an authentic being, that allows one to reach a state of mind in which the seeker may gently, sweetly and lovingly move into the deeper mind to find the seeds of the low self-esteem, the tendency to repeat patterns of addiction or abuse of various kinds given by parents which seemed godlike. Inevitably, either imitation or refusal to imitate figures of seeming authority in childhood forms the essence of your programming. One, having discovered to the best of one’s ability the nature of the trigger of self-destructive behaviors, can then, with enough passion, will and grace, reprogram the biocomputer. Let us give an example well known to this instrument. This instrument has a physical vehicle which has been created by its own choice in such a way that it shall do inner work. These seeming limitations, on the other hand, have been seen by this entity as opportunities. This leaves that artifact known among your peoples as pain. The instrument, therefore, realizing the distracting nature of pain, spent some time recently in reprogramming in order to fail to notice pain. In this way, when there is enough need, when there is a perceived suffering within the self, then one is motivated to do the very disciplined work necessary to reprogram. Remember that each of you is a co-creator. You have been created, but you have not been created imperfect. You have chosen to leave the house of the Father, to travel the circle path from source to source, from mystery to mystery. There is a program which can only be reached by one who is willing to do meditation and persevere, for in most cases this does take time. As one sits in meditation, day after day, year after year, one slowly becomes aware that one is more able than previously to discern intuitions and deep hunches. Thus, not only are you programmed for the tangible things, but, perhaps more importantly, for the intangible. Quite often, entities within your culture have a native programming of working hard, creating a safe amount of your money, and seeking that which is known as happiness. Happiness is entirely a portion of your illusion. For if the Creator is absolute, then so are you, [joy] is absolute. Have you found it today? Have you looked for it? You may encourage each other, exhort each other, comfort and console each other, and so minister to each other, that each mirrors a more and more accurate reflection of the other self and the self, so that there is constant opportunity to learn, to consider, and, when a behavior has been identified as not being congruent to the being, to move into that behavior and remove it from your programming, with the help of the deep portions of the mind, where dwell what we might call a metaprogram of divine inspiration, and a deep awareness of all that there is, then one may work in consciousness. One may have come to this point from different agendas. One entity may wish to be of more service, another may wish to avoid suffering. The reasons are as many as entities are. But truths do remain simple, and that which you seek, you shall find. Thusly, if you but persevere in the reprogramming, and request the aid of that vast metaprogram of enhanced knowledge not available to you as a personality, you become more and more able effectively to create your experience. The old question of the tree in the forest that we find in this instrument’s mind is quite apt here. That which you do not choose to perceive does not exist for you. Thus, it is quite important for the seeker of truth to identify those things which separate it from others, which cause distress to the self, and which limit love, and so speak to that necessity that effectual transformation results, more real, again and again, on ever deeper levels of bias, that may well be self-destructive in your own opinion, for you in your free will are anything but simple. When the programming, however, is to be tackled, it is well to become simple, single-minded and wholehearted, because you are asking yourself, in a subjective sense, partially to die, and to be no more. Thus, your faith that all will be well, and your will to continue spiritual evolution are the strengths and resources that bring you to holy ground, whereon the Creator, that lies so deeply within, in the metaprogram of love and infinite peace, is made available. Again and again you must seemingly retrace your steps. However, it is our opinion that this seeming repetition is in fact the peeling of the onion, layer by layer by layer. Many things which are self-destructive have only been kept because the programming is so deep. There are so many layers with which one must work, and one cannot fully reprogram one’s biocomputer unless one actually and in truth is ready to allow that portion of the personality to die. However, it is in that death that you find larger life, in this incarnation, or in any illusion. We would at this time transfer this contact, offering it first to the one known as K. It is perfectly acceptable if this instrument does not wish to speak, in which case we shall transfer to the one known as Jim. I leave you through this instrument in love and light, and with great joy. I am Q’uo. (Pause) (Carla channeling) I am again with this instrument and we find that neither of the other channels within this particular group wish (inaudible) this instrument wishes to complete the main message. This is acceptable to us and we shall continue through this instrument in love and light. (Pause) Greetings again from those of Q’uo. We have said that the most difficult thing one can do is to forgive oneself utterly. Most entities require some kind of structure, which seems to dispense understanding, enlightenment or redemption from without. These forces are without and within and as you are the only inhabitant of your creation and everything else is perceived through the ruthless economy of your biocomputer there is little or no hope of discovering truth using only an object which symbolizes worship. This is quite appropriate and acceptable as a path of inspiration, as a guide. However, you yourself are indeed in dominion over that which you wish to have in you. That which this instrument calls the Holy Spirit—which many call guidance, or guides or inner masters—is able at all times to allow one to rest and to be comforted. When one allows oneself, finally, to love the self very deeply and passionately, one is then ready to serve. For the one known as Jesus spoke—we must pause. I am Q’uo. This instrument is having some difficulty. (Pause) I am Q’uo, and we are again with this instrument. The master known to you as Jesus said that it was not he but the Father that strengthened him. So it is with you, eventually. You are more informed and more powerful in a personal sense than you realize quite often. You have by the grace of the one infinite Creator enlightenment, redemption and love of self alone, for the two requests that the one known as Jesus made to replace entirely the Ten Commandments were to love the Creator and to love other selves as the self. Consequently, it is essentially important to work with the self in consciousness until one realizes that regardless of the illusions in one’s own spiritual temperature-taking, it is not selfish or service to self but indeed necessary first to find charity towards the self. For you contain all within and if you do not feel self-forgiven how then can you feel in truth the joy of all being self-forgiven? How can you feel joy for the truth that is someone else’s and not your own? The hardest work that you can do within this incarnation is work in consciousness. Yet this work in consciousness is by far the most effectual means of accelerating in any spiritual evolution, innovating, enlightening the consciousness of your sphere, when you have no solemnity, no love, that many enjoy and so shall you, each of you, as you find you truly are a person to be esteemed, a person who has gifts and whose only desire is to offer them to the one Creator. Is this not a beautiful thing? Can you not step back and see the courage involved in having faith where there is no evidence to support it? Nor can there ever be, for this is the density of choice, blind choice. You work in the dark, you suffer, then discover the suffering, accept it, grasp its nature and eventually reprogram it over and over and over again, moving away from suffering and towards mindfulness not because you have behaved differently but because you have told your mind to register different portions of catalyst. Have you ever, for instance, purchased an object which you had not seen before but thought well of and then found in every nook and cranny someone else who had found the same thing. They had, of course, been finding that all along but you had not. So the information was not relevant to you and was simply [deleted] from conscious thought. (Side one of tape ends.) (Carla channeling) We find that as this instrument’s fatigue is great, it is well, in addition to each entity’s sore derrière, [that] we leave this instrument. We would like to attempt to crystallize the material we have offered you. Your universe is completely subjective and consists only of energy and magnetic fields. Within those vortices of magnetic fields rests by a slender thread an infinite consciousness. Your power cannot be seen by you, for you dwell in clothes of flesh and bone. Yet this power is within you. The mind is a kind of computer. It may be analyzed as to what choices it has made that are disruptive, unpleasant or inappropriate. Yet, one cannot change oneself from the outside in. One must first find the truth of oneself and then the truth of consciousness. Moving from that point, more and more aware of love being all that there is, the courage slowly becomes gained to allow self-destructive portions of the self to die that a new and more harmonious state of mind may be the response when one is faced with the choices of what to perceive. Never judge your behavior or your thoughts but rather be compassionate, openhearted and above all, persistent. And as you discover your beautiful self so will all others become beautiful. As you discover that you are all things possible, including all the negative things—the thief, the rapist, the killer—you then become aware of that great importance of choosing again and again for you cannot only perceive good so-called, you perceive in a full circle and have a full complement of abilities to act negatively and positively in the normally understood sense of those words. Take the leap of faith when you are ready, not before, and certainly not after for the adventure in this arena becomes much more interesting, we feel, for those who create rather than accept their own universe—we correct this instrument—universes. May you create yours and recreate yours gradually, persistently and with great love for the self as a spark of the infinite One until at last you are hollow through and through with no blockage to keep infinite light and infinite compassion from flowing through you. You are not a victim, but it is your choice which determines your perception. Choose well that which you desire, my friends. For as the cliché goes, yet it is true, “seek and ye shall find.” Be therefore careful of that which you seek. We are those of Q’uo, and would at this time transfer the contact to the one known as Jim in case there are any questions upon the mind of any present. Again we leave this instrument in love and light and service. I am Q’uo. (Jim channeling) I am Q’uo. I greet each again in love and light through this instrument. At this time it is our privilege to offer ourselves in the attempt to speak to those queries which may be upon the minds of those present. Again, we remind each that we do not wish to be considered in any degree infallible but wish to offer our thoughts and opinions freely, asking that you take those which ring of truth to you and use them as you will, leaving behind all others. Is there a query at this time? Questioner: This is one that we use. We were taught and it has been very effective in my experience to use the holy name of God to concentrate our minds at all times. It seems that from this type of doing I’ve been very much able to get rid of a lot of bad programming as we’ve been speaking of. How do you all view this? I am Q’uo, and am aware of your query, my brother. When one uses the sound vibration complex that you call name for the one Creator and give to that name your own acceptance and adoration then you provide for yourself a channel or a gateway into that portion of your being where this is true. For within each has the one Creator hidden Itself that through the expression of the individualized self the one Creator might know more of Itself and each portion of Itself might then partake in this discovery, one for the other, as the yearning for union grows. Is there another query, my brother? Questioner: Also, you spoke earlier of acknowledging the negativities or the positivity of one’s being in the programming of the biocomputer. This is not very clear. Could you restate it in another way so I might be able to understand it more easily? I am Q’uo, and I am aware of your query, my brother. It is often the case for many of your peoples as they look consciously and carefully at themselves that they will see those portions of behavior that they do not appreciate and consider to be less than worthy of study, those portions which may be seen as inability to love, the ability to give insult and injury, the less than honest expression of truth, and so forth. Oftentimes these characteristics are ignored or discarded, hoping in the ignoring of them that they will disappear. We suggest instead that they also be honored as portions of the self which have a role within the larger scope of the incarnational process and that such character traits or behaviors or beliefs might be followed to their source in order that the entity might discover a more complete picture of the nature of the self and the specific kind of balancing that is in process in the entity, for it is oftentimes true that the negative expression of a character trait is merely one end of a pole or a range where a more positive expression may be found if first the roots of both are uncovered. Is there a further query, my brother? Questioner: Thank you for that. I am Q’uo, and we thank you, my brother. Is there another query? Questioner: I’m not sure but I think my brother may have been asking about the idea of the—each person can have all various personality traits (inaudible) the full range (inaudible). Correct me if I am wrong. Questioner: The answer that was given was very good. I understand it to be that we have to follow those negative aspects of ourselves to find out from where they arise and in doing so we gain that greater knowledge of each of ourselves. I assume that’s what’s meant by exhibiting negative characteristics [and] outward demonstration. I am Q’uo, and this is correct, my brother. Is there another query? Questioner: My query is what density are you operating on and do you have access or perception of all other densities either through travel or exploration? I am Q’uo, and am aware of your query, my brother. We of Q’uo are what you might call a group mind or more correctly the blending of two such group minds for the purpose of making an entry into this particular group for the purpose of being able to communicate our thoughts in response to this group’s queries. This is the reason for the blending of two such groups in our case. We seek at that level of vibration which you would equate with the fifth density of experience or that which is of light where the limitless light of the one Creator shines in such a fashion that the truth of unity is without doubt and the relationships between various portions of the one Creator might be more clearly seen. We of Q’uo seek the lessons of unity, those lessons which are found within that density numbering six where those we call teachers reside. We may travel in thought to such locations and experience a portion of what is available there and as our point of viewing or ability to perceive is expanded by our own learning and experience then more of that which lies ahead on our path becomes available to our perception. Thus, we can speak from experience only through the density numbering five and must rely upon that which has been told to us by our teachers and those bits of our own perception where we have traveled in thought in relation to densities beyond our own. Is there another query my brother? Questioner: I was wondering, I have a teacher in this density also [that] I hold with great reverence and adoration. I call him by the name of (inaudible). In what density is he vibrating now on this planet? Or what density has he come from or descended into this incarnation, if you have that information? I am curious about that. I am Q’uo, and am aware of your query, my brother. We find a difficulty in giving a direct answer to this query for we do not wish to infringe upon the free will of any who revere this most positively-oriented entity. To describe such an entity by the density to those who honor this entity would be perhaps in some cases to skew this appreciation in an undue manner, which would obscure perhaps the message this entity had to offer. Each entity of this nature comes to serve those of this planetary vibration by hollowing the self in such a fashion that it becomes a pure and clear channel for the one Creator in order that information and inspiration of a certain nature may be offered. This is the message and the purpose of the incarnation for such an entity and each such entity wishes that the message might be delivered as clearly as possible with as little tendency towards distortion as possible. We humbly beg your forgiveness for being unable to give the density of this entity for we wish this entity’s message to remain as clear as possible. Is there another query, my brother? Questioner: No, I appreciate that answer. Thank you very much. I am Q’uo, and we thank you once again, my brother. Is there another query at this time? Questioner: Just on the off chance that you might give suggestion—when I do a reprogramming (inaudible) out what I wish to change and the reason involved and a kind of object that makes it, I suppose, more real psychologically and as I write it I vow and I request my mind to accept the new program and to dump the old one. Is there a number of different ways to do this or is there one that you would recommend? Have you any suggestions upon it? I am Q’uo, and I am aware of your query, my sister. There are as many ways of reprogramming one’s biocomputer as there are entities wishing to do so. The most potent program for any entity is that one which has been constructed from the pure desire found within the heart. The expression of this desire is that which gives form as a channel to that desire. This, however, is secondary to the successful reprogramming. The generation of this desire so that it is complete and fills the entity and overflows the cup, shall we say, is that which is of primary importance in the root—we correct this instrument—in the reprogramming of any thought or behavior pattern. If, as in your case, an entity finds it is helpful to form this desire by writing it upon the paper, by speaking it as a vow, by dancing it as a dance, praying it as a prayer, or meditating it as a mantram then this is the form that is appropriate for that entity. It is well to use those tools which one has been given in which one has found a certain degree of mastery in previous use in order that a form which is most effective might be utilized in giving the clear voice to this heart-generated desire for a closer approximation of love within the life pattern. Is there a further query, my sister? Questioner: No, I’m done. Thank you. I am Q’uo, and again we thank you, my sister. Is there another query? Questioner: You mentioned the deep mind and I was wondering what are the symptoms of reaching the megamind or the infinite intelligence and whether one can actually be in that awareness or consciousness all the time within this density, third-dimensional density? And the symptoms, of course, you can elaborate on and can maybe give a clue to the path to tapping into that gateway that we can manifest greater love and light of the infinite Creator which I call Krishna. That is my question. Thank you. I am Q’uo, and we are most appreciative of this question which ranges quite broadly within the field of the evolution of consciousness. To give a full answer would be the work of many sessions such as this one but we may give a, shall we say, a crystallized response and ask that further queries be given if there is more information desired. The ability of any entity to reach deeper levels of the subconscious mind and move therefrom to other levels of mind which would include the racial, the planetary, the archetypical, and the universal mind depends upon the ability of the entity to still the conscious mind to such a degree that silence is able to prevail and open a door that is more clearly seen, or shall we say, felt, due to the lack of interference in the activity of the mind. This ability to move through this doorway to deeper levels of the mind is a, shall we say, product of work done upon the personality. This includes work at each level of existence that corresponds with each chakra or energy center as you know them within the physical vehicle, each center allowing the entity the opportunity of more fully expressing the intelligent energy or prana of the one Creator. It is within each center or chakra that various blockages have been programmed before each incarnation to bias the learning of the entity in such and such a fashion. As this learning proceeds apace the entity is able to see the self, all other selves, and the creation and experiences about it as those expressions of love which have for some time been disguised as other than love. Therefore, the greatest indication or symptom of an entity able to move through deeper levels of mind is the ability of the entity to see love in all portions of the creation. This is a product of a great deal of work over many periods or incarnations for the seeker of truth. We feel that this is a great deal of information which if added to at this time might be somewhat confusing, therefore we shall allow any further query that you would have at this time. Questioner: I have one more query. The bias towards learning or the biases that are created within the consciousness for learning I’m being taught more is, even though [it] sometimes creates in our experience pain—what we experience is pain or the illusion of suffering is also perfect in the eyes of the Creator and the consciousness of the higher self … (Pause) I am Q’uo, and we feel that we have the gist of your query and would agree that though much learning partakes in that which appears to be great suffering, disease, poverty, pain and separation one from another that these are often the most effective means of directing the attention which has not focused clearly upon the lessons at hand. The catalyst of pain, for example, is that which grabs your attention and points towards an area which contains the opportunity for uncovering a portion of the self which waits to be born. With each birth there is the pain of the delivery. That which is old and has been replaced by that which grows anew oftentimes must be allowed to be removed in a painful fashion. Since the illusion in which you move has many veils across the far-seeing ability of any entity, it is necessary oftentimes that the eyes which see only dimly be given the assistance or the reminder that trauma and suffering provide. However, when the pearl has been won, no price or pain is too great. At this time we feel that we have extended the energies of this group far enough that it would be well to give rest. Therefore, we shall once again thank each for inviting our presence and shall leave this group as we have found it in the love and in the light of the one infinite Creator. We are known to you as those of Q’uo. Adonai, my friends. Adonai. | Mid | [
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China frees Vatican-affiliated Chinese bishop: sources Beijing (AFP) – Chinese police have released an underground bishop after holding him for a day, sources told AFP on Wednesday, as Beijing and the Vatican prepare to seal a historic agreement on the appointment of prelates. Vincent Guo Xijin, bishop of the diocese of Mindong in the southeastern province of Fujian, was at the centre of the controversial deal after being urged by the Vatican to step aside for a prelate recognised by China’s Communist government. He was detained on Monday, a Catholic source close to the matter told AFP, though it was not clear why. “He has returned home. He was taken away on Monday evening and returned on Tuesday evening,” the source said, requesting anonymity to avoid repercussions. An Amnesty International researcher in Hong Kong, Patrick Poon, also cited sources as saying Guo was released after being held for “talks”. The detention was first reported on Tuesday by AsiaNews, which is run by the Pontifical Institute for Foreign Missions. The AsiaNews report said Guo was detained along with another official of the diocese. The status of the second official is unclear. Contacted by AFP, both the local Chinese police and the Fujian provincial office of religious affairs said they were unaware of the arrests. The Vatican has not commented on it. Beijing and the Vatican severed diplomatic relations in 1951 and although ties have improved as China’s Catholic population grows, they have remained at odds over the appointment of bishops. China’s roughly 12 million Catholics are divided between a government-run association, whose clergy are chosen by the Communist Party, and an unofficial church which swears allegiance to the Vatican. The situation is complex because the Vatican has previously accepted several bishops appointed by Beijing, officially an atheist regime. Guo, 59, is recognised by the Vatican but not by the Chinese authorities. He was recently urged by the Vatican to step aside for Bishop Vincent Zhan Silu and to accept being demoted to auxiliary bishop, as part of preparations for the agreement. According to Catholics consulted by AsiaNews, the disappearance of the bishop of Mindong can be explained by his refusal to celebrate Easter with the prelate who will replace him. The site also reported that this same bishop disappeared for 20 days last year. Poon said the Chinese government must urgently explain why Guo was held. “What is meant by ‘talks’ in the Communist Chinese context is always about detention and threats unless the government can really explain why Bishop Guo was required to attend the ‘talks’,” Poon told AFP. According to information from the French daily La Croix published Monday, a Chinese delegation is expected in Rome this week. | Mid | [
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Vegan Caviar - Ideal for people catering to guests and are unsure if attendees are on a Vegan diet. Makes a perfect gourmet food, to add elegance for Vegan or Vegetarian events. This caviar resembles Russian Beluga Caviar in size, color and appearance. This item makes a great gift for those who are looking to add wealth and elegance to the table without actually having to eat fish product. It has a delicious salty, buttery flavor with jet black color, and a pleasant aroma. You might find yourself eating it by the pounds. Shelf Stable for six months at cool room temperature. Has one year shelf life in the fridge. Buy Delicious Vegan Caviar in Redkey, Indiana. We are proud to supply all of Indiana with our large caviar selections and gourmet foods. We strive in making it simple for Indiana customers not only to get the highest possible quality, but at affordable prices delivered right to their door. We provide FedEx Overnight shipping (including Same Day, Every Day caviar delivery Throughout Los Angeles, California.) Also providing Saturday delivery throughout Redkey, Indiana and all of the United States. Area codes in which we supply fresh American caviar of Black caviar and salmon caviar include: | Mid | [
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Gastrointestinal complications of aortic bypass surgery. Gastrointestinal bleeding following abdominal aortic bypass surgery is not uncommon, as approximately 20% of patients with abdominal aortic aneurysms have peptic ulcer disease. We have recently seen three patients who presented with gastrointestinal bleeding secondary to the complications of their surgery. The cause of the bleeding was aortoduodenal fistula, graft erosion into the sigmoid colon and ischaemic colitis respectively. The correct diagnosis was only considered in one patient, although in retrospect it should have been suggested in all three. Our experiences with these complications and their clinical and radiological presentation form the basis for this paper. | Mid | [
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The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. Introduction and background =========================== The epidemic of cigarette smoking (CS) is one of the largest public health threats and one of the leading causes of preventable deaths, globally. Tobacco kills more than seven million people every year \[[@REF1]\], out of which 480,000 deaths per year are in the United States (U.S.) alone \[[@REF2]\]. There are over 7,000 chemicals in tobacco smoke, and more than 250 of those toxins are known to be carcinogenic. These include polycyclic aromatic hydrocarbons (PAHs), cadmium and beryllium (toxic metals), hydrogen cyanide, carbon monoxide, and ammonia \[[@REF3]\]. There are many forms of tobacco in the market, including cigars, electronic cigarettes, hookah (water pipe), as well as bidis, which are flavored cigarettes. However, there is no safe form of tobacco, and all of them can cause severe health problems, which include neoplasms, cardiovascular issues, and respiratory problems, such as obstructive and restrictive lung disease \[[@REF2]-[@REF3]\]. Approximately 40% of all cancers diagnosed in the U.S. are due to the use of tobacco \[[@REF4]\]. The dose, type of tobacco, route of nicotine delivery, and chronicity of irritation exposure to the cancer-prone area are all determinants of cigarette smoke on the health outcome of an individual \[[@REF5]\]. Studies have shown that the risk of cancer is directly proportional to the number of cigarettes smoked per day and the duration of chronic smoking \[[@REF6]\]. However, each cigarette contains approximately 10 milligrams of nicotine, which is a highly addictive substance \[[@REF3],[@REF6]\]. Currently, about 37.8 million adults smoke in the U.S. \[[@REF2]\]. Out of those, 70% would like to quit but are not able to do so due to withdrawal symptoms, including irritability, depressed mood, restlessness, and anxiety \[[@REF3]\]. Recent studies have shown that CS may lead to cancers in the oral cavity \[[@REF7]\], esophagus \[[@REF8]\], lung, stomach \[[@REF9]\], pancreas \[[@REF10]\], kidneys \[[@REF11]\], and the bladder (bladder cancer; BC) \[[@REF12]\]. The carcinogens found in the cigarettes may lead to DNA damage \[[@REF13]\], impaired DNA repair mechanism \[[@REF14]\], and a weakened immune system, which further leads to inflammation and infections \[[@REF11]\]. CS causing impaired immunity in the oral cavity ultimately leads to oral cancer (OC) \[[@REF7]\]. Over time, the superficial ulceration of a mucosal surface in the oral cavity develops, and it may become an exophytic mass (EM), or tumor, which tends to grow outward beyond the surface epithelium from which it originates \[[@REF15]\]. If the initial ulceration, or lesion, is left untreated or the irritant is not removed, it can progress to carcinoma of the surrounding tissues, as in oral squamous cell carcinoma (OSCC) \[[@REF16]\]. By contrast, in the development of esophageal squamous cell carcinoma (ESCC), through a multi-step process of epigenetic and genetic changes, a sequence of histological changes occurs in the epithelium of the esophagus, over years of chronic irritation due to tobacco smoking \[[@REF17]\]. Studies have shown that the nicotine from smoking may increase the gastric aggressive factors and attenuate the gastric defense mechanism, which results in gastric ulcers (GUs) and leads to gastric adenocarcinoma (GAC) \[[@REF18]\]. The exact etiology of renal cell carcinoma (RCC) is unknown; however, there are many known risk factors, which include obesity, hypertension (HTN), family history, advanced kidney disease, and CS \[[@REF19]\]. CS is the major cause of urothelial cell carcinoma (UCC) as well \[[@REF12]\]. This article focuses on CS-associated cancers and their pathogeneses. Review ====== Oral cancer associated with CS Squamous Cell Carcinoma of the Oral Cavity The Centers for Disease Control and Prevention (CDC) reported that in 2012, there were nearly 40,000 new cases of cancer involving the oral cavity and pharynx, which resulted in nearly 9,000 deaths in the U.S. and was deemed the sixth most common cancer worldwide \[[@REF20]-[@REF21]\]. Tobacco use in the form of smoking cigarettes, smokeless tobacco, cigars, and chewing tobacco directly affect the oral cavity, which may lead to OSCC \[[@REF7]\]. The oral cavity is the first site exposed to the carcinogens found in tobacco products, inevitably resulting in an increase in incidences of OC \[[@REF5]\]. The effect of CS on human immunity depends on multiple variables, including the dose and type of tobacco, the route, and chronicity of the exposure \[[@REF5],[@REF7]\]. Cigarettes deregulate the immune response against pathogens and antigen presentation, therefore promoting autoimmunity throughout the body \[[@REF7]\]. The deregulation of the immune response by a heightened or suppressed inflammation (due to CS) in the mucosal surface and the modulated microvasculature affects healing and resolution of inflammation \[[@REF5],[@REF7]\]. Consequently, impairment of the oral cavity immune response serves to promote OC \[[@REF7]\]. The OSCC may arise anywhere within the oral cavity. The most common location is the ventral surface of the tongue, the floor of the mouth, lower lip, soft palate, and the gingiva \[[@REF16]\]. Early OSCC presents as leukoplakia, which may lead to erythroplakia, or even erythroleukoplakia, which is a mixture of red and white lesions on the tongue or mucosal surface \[[@REF15]\]. Leukoplakia has no histopathological connotation and is not used as a microscopic diagnosis; however, it is instead used as a marker to take a biopsy for further investigations \[[@REF7],[@REF15]\]. Over time, superficial ulceration of the mucosal surface develops, and it may become an EM \[[@REF15]\], and if left untreated, or the irritant is not removed, it can progress to OSCC \[[@REF16]\]. The most common site for the cancer is the tongue, on the posterior-lateral border, or on its ventral surface \[[@REF15]\]. The lateral tongue and floor of the mouth combine to form a region of the oral mucosa that includes the tonsillar area and the lateral soft palate \[[@REF7],[@REF15]\]. This region has a high-risk factor because many of the tobacco carcinogens mix with saliva and then pool at the bottom of the mouth; this leads to chronic irritation of this site \[[@REF7],[@REF15],[@REF22]\]. Furthermore, this region of the mouth is covered by a thin, nonkeratinized mucosa that provides less protection against carcinogens \[[@REF15],[@REF22]\]. OSCC has a risk of metastasis; when the cancer cells enter the vascular or lymphatic channels and into the cervical nodes, metastasis can occur \[[@REF21]\]. The most common areas of metastasis are the lungs, lymph nodes, liver, and bones \[[@REF15],[@REF21]\]. Treatment options are similar to the treatment of other cancers, which are variable, and depend on the following: the size and location of the primary tumor, lymph node status, and the presence or absence of metastases. Surgery and/or radiation therapy is the gold standard for cancers of the lip and oral cavity \[[@REF23]\]. For advanced stages, surgery with radiation therapy may be warranted \[[@REF21],[@REF23]\]. Esophageal cancer associated with CS Squamous Cell Carcinoma of the Esophagus EC has become an increasingly common and lethal malignancy. According to the CDC, "a total of 81,608 new cases (4.6 per 100,000 people) of EC were reported in the U.S. during 2010-2014" \[[@REF24]\]. ESCC is the most common type of EC globally \[[@REF8],[@REF24]\]. The incidence of ESCC increases with age, occurring mostly in the seventh decade of life, and most often in the middle and lower esophagus \[[@REF17]\]. The high-incidence area for ESCC is associated with the "Asian EC belt," which is from Central China, East Asia, into Iran \[[@REF8],[@REF17],[@REF24]\]. In the high-incidence area, about 90% of the ECs are ESCC, versus in North America, in which less than 30% are \[[@REF8],[@REF17]\]. The leading risk factors for ESCC in Western countries is tobacco smoking \[[@REF8]\]. Studies have shown that chronic tobacco smokers have a relative risk of 2.5-4 folds of developing ESCC than those who have never smoked tobacco products \[[@REF25]\]. Recent studies have shown that having tobacco exposure at a young age, or with high intensity and accumulative consumption, further increases the risk of developing ESCC \[[@REF17],[@REF25]\]. The long-term irritation of the esophagus by the carcinogens in tobacco smoke has a damaging effect on the DNA in the squamous cells that line the inside the esophagus. Cigarette smoke contains free radicals and induces oxidative damage \[[@REF14]\]. The damaging effect on DNA from the constant irritation by the carcinogens affects the cytochrome 450 (CYPs) enzymes. The CYPs catalyzes an oxygen atom onto a carcinogen, to increase its water solubility and convert into a form that is readily excretable. However, with persistent cigarette smoking, some of the intermediates (the carcinogens) that are formed by the interaction with CYPs are reactive, and when react with DNA, result in DNA adducts \[[@REF25]\]. DNA has an elaborate repair system to eliminate DNA adducts from the genome; however, if the repair mechanism fails, due to irritant overload such as tobacco use, it can lead to mutations, which increases the risk of cancers \[[@REF14]\]. The ESCC develops through a multi-step process of epigenetic and genetic changes, leading to a sequence of histological changes in the epithelium of the esophagus over years of chronic irritation, in this case by tobacco smoking \[[@REF17]\]. The histological changes of the esophagus begin with esophagitis, then basal cell hypertropia, dysplasia, and carcinoma in situ, ultimately leading to ESCC \[[@REF8],[@REF25]\]. The esophagus lacks serosa and without an anatomical barrier, the primary tumor can spread rapidly into adjacent structures of the neck and thorax \[[@REF17]\]. The prognosis of ESCC depends on the local invasion, as well the spread to regional and distant structures within the body. ESCC has a high risk of invading the thyroid gland, trachea, larynx, lung, pericardium, aorta and diaphragm \[[@REF8]\]. Once ESCC has invaded the surrounding structures, a patient presents with dysphagia for liquids at first, and consequently experiences progressive dysphagia including solid food, due to the growth of cancer \[[@REF17]\]. As a result, odynophagia occurs due to the obstruction by cancer, resulting in weight loss, due to lack of nutrition \[[@REF8],[@REF17]\]. Other complications that may occur, depending on the location of cancer, may include the following: bleeding, epigastric pain, hoarseness, persistent cough as well as respiratory symptoms, such as difficulty breathing. However, patients may remain asymptomatic until malignancies have already occurred \[[@REF17]\]. ESCC is known to be aggressive by nature through its spread by a variety of pathways including the lymphatic system and hematogenous metastasis \[[@REF8],[@REF17]\]. The lymphatic drainage of the esophagus is by two separate lymphatic plexuses. One arises within the mucosal layer and the other arises from the muscular layer. The lymphatic fluid from the upper two-thirds of the esophagus drains up, while the lymph from the lower one-third of the esophagus drains down; however, all the lymphatic channels of the esophagus still communicate \[[@REF14],[@REF17]\]. The lymphatic fluid from any portion of the esophagus may spread into the intra-thorax or intra-abdominal lymph nodes, resulting in metastases \[[@REF8],[@REF17]\]. The prognosis for patients diagnosed with ESCC is poor. Approximately 10% of patients survive five years after the diagnosis; thus, the approach of patient care is primarily focused on the management of controlling symptoms. Current treatment options include surgery, radiation, and chemotherapy \[[@REF17]\]. Lung cancers associated with CS Small Cell Lung Carcinoma SCLC is a carcinoma of the lungs, which is very aggressive and has rapid growth and an early metastasizing pattern \[[@REF26]\]. About every two-thirds of the people, when already diagnosed with SCLC, have this carcinoma in its extensive stages \[[@REF27]\]. This carcinoma arises from the neuroendocrine cells and is known as "Oat Cell Carcinoma" due to its appearance. On the microscope, this carcinoma appears pale and grayish, while the cells are oval-shaped, therefore resembling an oat \[[@REF26]-[@REF27]\]. These cells are highly malignant and have a very thin cytoplasm and fine granular chromatin. SCLC is a centrally located mass of the lungs. It has an early metastasizing effect into the lung parenchyma and most commonly involves the hilar and mediastinal lymph nodes. SCLC accounts for about 10% to 15% of all LCs \[[@REF28]\]. There have been a total of 234,030 new cases and 154,050 deaths due to LC in the U.S. alone. The good news is that since the smoking rates have been declining over the past few years, the incidence of SCLC is decreasing. The manifestation usually occurs around the age of 60-80 years and most commonly affects males. This is mainly due to the fact that smoking is the leading cause of SCLC and makes up about 98% of cases \[[@REF9]\]. Epidemiological studies have shown that males generally smoke more than females; hence, the risk of developing SCLC is much greater in males than females. Another reason is that males tend to more often work in factories and are therefore exposed to chemicals like radon, asbestos, and uranium, which puts them at a higher risk \[[@REF9],[@REF27]-[@REF28]\]. SCLC more commonly arises in the later decades of life which is due to the fact that smokers more often have had exposure to smoking their entire lives. This demographic causes gradual damage to their lungs over time while allowing for an adequate recovery period for their lungs to regenerate from the lifelong effects of cigarette smoke \[[@REF9],[@REF27]\]. Since the most common risk factor for SCLC is smoking, it is rare to see a patient present with a different cause. Some other risk factors include exposure to other harmful chemicals, second-hand smoke, and a family history of SCLC \[[@REF27]\]. Any type, whether it may be cigarette smoke, pipe smoking, cigar, electronic CS, and even low-tar cigarettes, are all just as likely to cause SCLC. The longer one smokes and the greater the amount that is smoked will each be a factor in how much higher the chance of developing SCLC is. If smoking is stopped, the probability of survival will likely rise, thus the risk of getting SCLC will improve, or decrease \[[@REF9]\]. The development of SCLC depends on the extent of the lung damage due to smoking. Smoking damages the lining of cells in the lungs, which makes the lungs weaker and affects tissue. Although the body can repair damage for the carcinogens that enter it, the healing capacity of the body decreases, which leads to the further damage of tissue. So, over time, the accumulation of tobacco smoke that has harmed the lungs, and irreparable damage leads to diseases like SCLC \[[@REF9],[@REF27]\]. The development of SCLC also leads to some paraneoplastic syndromes that are associated with it, due to inappropriate secretion of some hormones which can also manifest as other diseases. With cancer, organ and tissue function are affected, and that affects the normal processes of the body. The body, for example, produces excessive amounts of antidiuretic hormone (ADH), leading to SIADH, a condition that causes the body to retain water \[[@REF9],[@REF28]\]. Another manifestation associated with SCLC is Cushing's syndrome which is due to excessive secretion of adrenocorticotropic hormone (ACTH) \[[@REF9]\]. Most patients are asymptomatic at early stages, but in the advanced stages of SCLC, will present most commonly with shortness of breath, hemoptysis, fatigue and weight loss \[[@REF9],[@REF28]\]. The most common treatment of SCLC includes a combination of chemotherapy and radiation therapy. Combining of the two will increase the survival rate and prolong the life of the patient because they both work to stop the spread of, and kill, cancer. Chemotherapy works by preventing the disease from spreading, while radiation uses high-energy particles to destroy the cancer cells. Surgery is not recommended due to the fact that this cancer can spread very fast; for even just by the time of diagnosis, resection from only one place will not be sufficient to get rid of cancer \[[@REF28]\]. Non-Small Cell Lung Carcinoma Adenocarcinoma: Adenocarcinomas are non-small cell lung carcinomas (NSCLC) and are the most common cause of primary LC. NSCLCs make up 80% of all LCs and 40% of those are due to adenocarcinomas \[[@REF26],[@REF28]\], which arise from the glandular cells of the outer portion of the lung, leading to a peripherally located mass \[[@REF28]\]. The glandular cells help secrete mucus, which is needed as a protective covering to help fight against foreign particles from entering the lung. It also shows columnar cells that grow along the lines of bronchioles and alveoli. An adenocarcinoma is a slow-growing cancer and is usually diagnosed before it spreads, which makes its prognosis better than most LCs \[[@REF4]\]. There have been 218,527 new cases of lung and bronchus cancer in the U.S. reported as of 2015, and 153,718 resulted in death \[[@REF20]\]. Although rates of LC are slowly dropping, adenocarcinoma is found to be the most common type of LC found in females. Female prevalence may be due to the fact that women began smoking later in life compared to men and then continued to smoke when men began to stop \[[@REF28]\]. The adenocarcinoma is the most common LC in non-smokers, even though smoking is one of its risk factors. Smoking damages the cell lining of the lungs. This harm over time causes the lungs to lose their ability to fix the scarring having occurred on the lung, which is when adenocarcinoma can arise. Adenocarcinoma that has spread can occur due to a mutation in the genes of Kirsten rat sarcoma viral oncogene homolog (K-RAS), epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK). A mutation in the gene of K-RAS is most associated with smoking and accounts for about 25% of cases. Meanwhile, EGFR and ALK are not related to smoking \[[@REF29]\]. Testing for these gene mutations will ultimately determine the appropriate treatment to go forward with when treating adenocarcinoma; hence, if the K-RAS mutation is present, that would indicate that the anti-EGFR treatment will not work. The anti-EGFR treatment is commonly used in adenocarcinoma of the lung that is spread widely in the body \[[@REF28]-[@REF29]\]. Adenocarcinoma patients present most commonly with hemoptysis, cough, chest pain, weight loss, and fatigue \[[@REF28]\]. The treatment options for adenocarcinoma widely depend on the stage of the cancer. If it is still localized and has not metastasized, then surgical resection is the best option. Sometimes chemotherapy is used first to stop the growth and then surgery is used to resect the tumor. Finally, if cancer has spread past the lungs, then chemoradiation would be used to stop the spread and kill cancer cells, followed by surgery if it is needed. Also, if cancer has metastasized, testing for gene mutations will help treat those that require the anti-EGFR treatment followed by surgery \[[@REF28]-[@REF29]\]. Squamous cell carcinoma: The consumption of tobacco products by smoking cigarettes, pipes, and cigars is the leading cause of LC \[[@REF21]\]. The American Cancer Society reports that NSCLC, including squamous cell carcinoma of the lung (SCCL), account for about 80% to 85% of LCs \[[@REF28]\]. It was previously the most common type of LC, but in many countries, it has declined over the past four decades, with a rise of adenocarcinoma of the lung instead \[[@REF20]\], now being the most common. SCCL is seen more frequently in male smokers \[[@REF30]\] and arises after decades of exposure to smoking. SCCL is preceded by the development of squamous dysplasia or metaplasia in the bronchial epithelium over years \[[@REF31]\]. If the irritant is not removed, the squamous metaplasia can transform to carcinoma in situ, and eventually SCCL \[[@REF28],[@REF31]\]. SCCL arises centrally in the major bronchi as a small neoplasm and eventually spreads to the hilar group of lymph nodes \[[@REF31]\]. The small neoplasm becomes symptomatic, and a well-defined tumor mass continues on to obstruct the lumen of a major bronchus, often producing atelectasis and infection \[[@REF30]-[@REF31]\]. Large lesions may undergo central necrosis and give rise to cavitation \[[@REF31]\]. SCCL shows keratinization and/or intercellular bridges that arise from the bronchial epithelium, due to the squamous metaplasia \[[@REF30]-[@REF31]\]. SCCL has a high probability of metastases to other parts of the body, due to the constant flow of fluids, such as blood and lymph, through the lungs, which carry cancer cells to nearby areas \[[@REF32]\]. A complication of SCCL is the development of Pancoast tumors in the upper lobe, where it can compress blood vessels and nerves \[[@REF31]-[@REF32]\]. This can ultimately damage the thoracic inlet, brachial plexus, and the cervical sympathetic nerve, resulting in Horner syndrome, manifesting as miosis, ptosis, anhidrosis, as well as enophthalmos \[[@REF30]-[@REF32]\]. Treatment of SCCL heavily depends on the stage the cancer is in and the patient's overall health. Treatment includes surgery, radiation therapy, chemotherapy, and immunotherapy \[[@REF30]\]. Gastric cancers associated with CS Gastric Adenocarcinoma Gastric adenocarcinoma (GAC) is the fourth most common cancer of the gastrointestinal system and the third leading cause of global cancer-related death. Approximately 1,000,000 individuals are diagnosed with GC annually, resulting in 800,000 deaths a year \[[@REF33]\]. The pathogenesis of GC is multifactorial; however, studies have shown that smoking plays a critical role in the manifestation of this cancer. The most common type of GC associated with smoking is GAC. They are classified by Lauren's criteria into two major histological subtypes, namely the intestinal and diffuse types. In intestinal type adenocarcinoma, tumor cells exhibit adhesion and are arranged in tubular or glandular formation. This type is often associated with intestinal metaplasia and commonly affects the gastric antrum \[[@REF33]-[@REF34]\]. In contrast with intestinal adenocarcinoma (IAC), the diffuse type adenocarcinoma cells lack adhesion infiltrate in the stroma as a single cell or a small subgroup, resulting in a population of non-cohesive, scattered tumor cells. The diffuse type exhibits more aggressive features as compared to the IAC \[[@REF33]\]. Although *Helicobacter pylori (H.pylori)* infection is the most common cause, smoking has been found to have increased the risk of GAC. Studies have shown that the nicotine from smoking may increase the gastric aggressive factors and attenuate the gastric defense mechanism, resulting in GUs, which then leads to the GAC. Smoking increases the gastric acid secretion by histamine or pentagastrin, rather than basal acid secretion \[[@REF18]\]. The increase in gastric acid decreases the pH of the gastric mucosa, which leads to the activation of pepsin since the activity of pepsin is highly dependent on the gastric pH \[[@REF33]\]. The long-term effects of smoking cause the inhibition of the mucus secretion from the gastric epithelium, which is a protective barrier against gastric acid. The combined effects of histamine and pepsin in increasing the gastric acid production, and decreasing the pH, acutely cause erosion of the mucosal layer. This may result in chronic GUs and hemorrhages, which may lead to GAC \[[@REF18],[@REF33]\]. The reactive oxygen species (ROS) are well documented to be involved in the pathogenesis of gastric inflammation, ulcerogenesis, as well as carcinogenesis \[[@REF35]\]. Kalra et al. found that there is a significant increase in ROS activation in smokers compared to non-smokers, suggesting that ROS may promote mucosal injury in smokers \[[@REF36]\]. Chronic smoking also stimulates the secretions of vasopressin, which is a potent vasoconstrictor, by activating central nicotinic cholinergic projections to the hypothalamus \[[@REF37]\]. The vasopressin causes generalized vasoconstriction, which decreases the blood flow to the gastric mucosa. This results in tissue hypoxia, which leads to gastric injury and a slow healing process \[[@REF18]\]. The tumor protein p53 (TP53) gene provides instructions to make tumor protein p53 (or p53), which acts as a tumor suppressor. The p53 protein binds directly to the DNA, and when there is DNA damage, the p53 activates other genes to either repair the DNA damage, or activate the apoptosis pathway, if DNA is not repairable \[[@REF13]\]. The TP53 is the most frequently mutated gene in GCs, exhibiting aberrations in approximately 50% of cases \[[@REF33]-[@REF34]\]. The long-term effects of tobacco smoking have been associated with an increased TP53 gene mutation, which impairs the DNA repair mechanism, resulting in abnormal proliferation of the cell, which leads to tumor growth \[[@REF13]\]. The treatment includes surgical approach based on the location of cancer, size, and tumor extent. The chemotherapy and radiotherapy can be used, and often time recommended, before surgery to improve the outcome of intended surgery. In advanced cases, palliative care is offered \[[@REF18],[@REF21]\]. Pancreatic cancers associated with CS Pancreatic Adenocarcinoma The pancreas is an organ in the abdomen that is located behind the stomach and is pear-shaped \[[@REF10]-[@REF11]\]. The cancer of the pancreas is known to be highly invasive and has a very strong association to tobacco smoking. PAC starts when cells from the tissue of the pancreas start to grow uncontrollably and become cancerous \[[@REF10]\]. The pancreas contributes to both endocrine and exocrine functions, playing a vital role in the body. It secretes the hormones insulin as well as glucagon, which are important in maintaining balanced blood glucose levels in the body to keep it functioning well. It also secretes enzymes such as lipase, amylase, chymotrypsin, and trypsin to help break down food in the digestive tract for proper digestion and absorption \[[@REF38]-[@REF39]\]. This carcinoma tends to spread fast to other parts of the body, for instance, the lymph nodes, lungs, liver, and bones. The most common place for lesions for adenocarcinoma is in the small ducts and ductules and is then called the pancreatic intraepithelial neoplasia (PanIN) \[[@REF38]\]. PC has one of the highest mortality rates. There have been over 44,000 American PC diagnoses in the year 2010 \[[@REF38]-[@REF39]\]. Gender does not have an effect on who would more likely get cancer, but the average age of the development of PAC is above 45 years of age \[[@REF38]\]. The pancreas can have cancer cells arising from either the exocrine or endocrine portion, although 95% of them arise from the exocrine portion, which means that the digestive juices that help in absorption and digestion are affected most \[[@REF38]-[@REF39]\]. Tobacco smoking is the most common risk factor for PAC, accounting for about 20% to 25% of PCs \[[@REF10],[@REF38]\]. Smoking is one of the most common causes of PC, for not only does it increase the risk factor for pancreatic cancer, but it also accelerates the progression for malignancy. Other risk factors include obesity, diets associated with high fat, a history of pancreatitis, and diabetes \[[@REF39]-[@REF40]\]. PAC generally arises due to the consequence of a cancer-associated mutation that is acquired or inherited. There are four confirmed genes most commonly affected, which are the KRAS, cyclin-dependent kinase inhibitor 2A (CDKNA2A)/p16, SMAD family member 4 (SMAD4), and TP53. The cause for these changes is not yet known, but these gene mutations are ways cancer arises and begins to grow \[[@REF38]-[@REF40]\]. PAC usually stays silent until it spreads or extends to impinge on another structure. Symptoms that a patient with PC may present with most likely start with pain in the upper abdomen that may radiate to the back, weight loss, early satiety, depression, and fatigue \[[@REF38]-[@REF39]\]. Some complications of PAC include the development of obstructive jaundice and a Courvoisier gallbladder \[[@REF39]\]. Unfortunately, when patients present with these symptoms, the disease progression is quite far, and most are not resectable, resulting in a poor prognosis. The treatment for PC is primarily surgery and secondly, is chemotherapy. Removal of the cancer cells before metastasis offers the best prognosis. If cancer has spread past the pancreas, then chemotherapy and radiation should be used. Chemotherapy works throughout the body by preventing dividing cells from spreading further by helping to kill them, and radiation helps by the destroying cancer cells using a high energy wave \[[@REF38],[@REF40]\]. Renal cancers associated with CS Renal Cell Carcinoma RCC is the most common type of kidney cancer in adults and has a strong association with smoking. RCC is formed when cancer cells located in the tiny proximal tubules of the kidneys begin to grow uncontrollably. These tubules help with the filtering of blood and getting rid of toxic waste products that will ultimately be excreted as urine \[[@REF41]\]. The tubules are lined with a simple cuboidal epithelium and have a border covered with microvilli, and when this area is compromised by RCC, the functions of absorption and secretion are compromised \[[@REF28],[@REF41]\]. RCC is the most common type of kidney cancer in adults and accounts for 90% to 95% of abnormal tissue growths in the kidney. There have been about 65,000 RCC cases annually, with 13,700 resulting in death \[[@REF19]\]. The cases generally peak around the ages of 50-70 years old, and males tend to be affected more than females, although it is not limited to those parameters \[[@REF19],[@REF41]\]. A risk factor associated with RCC is HTN, which males tend to be at a higher risk to develop. Men are also noted to smoke more than females, and they are more likely to be exposed to cancer-causing chemicals at work, making them at a higher risk of developing RCC \[[@REF19],[@REF42]\]. The exact etiology as to why RCC form is unknown, although there are many known risk factors, which include smoking, obesity, HTN, a family history, and having advanced kidney disease \[[@REF19]\]. The risk from smoking depends on the amount smoked. The chronic smoker will have a greater risk over the occasional smoker to develop RCC. RCC can be described in five different forms, namely the following clear cell carcinoma (CCC), papillary tumors (PTs), chromophobe tumors (CTs), oncocytomas, and collecting duct. Each of these types has specific histological features and distinguishing locations, which differentiates them from one another \[[@REF19],[@REF43]\]. CCC is the most abundant type, making up for about 60% of the cases, and is located in the proximal tubule. The CCC histologically appears clear and shows an acinar or sarcomatoid cell (SC) growth pattern and tends to have a very good response to treatment \[[@REF19]\]. PTs make up 5% to 15% of cases and show a growth pattern of papillary or SCs histologically and are also located in the proximal tubule \[[@REF19],[@REF42]\]. CTs present as solid or tubular cells histologically, are a less aggressive form of RCC, and make up about 5% to 10% of cases. They are less aggressive because of their large size, compared to the other types, and due to the size, they are not able to spread past the kidneys. CTs are located in the distal tubules of the kidney and the cortical collecting duct. Oncocytomas are present in the cortical collecting ducts and show a nest tumor-type growth, make up 5% to 10% of cases each, and are also a less aggressive form since they tend not to spread past the kidney. Lastly, the rarest and toughest form to treat, making up less than 1% of cases, is collecting duct RCC. It presents with a papillary or SC growth pattern, and it originates in the medullary collecting duct \[[@REF19]\]. CS doubles the risk of RCC due to the fact that it slows the blood flow to the kidneys. There is generalized vasoconstriction that ultimately results in the kidneys' function to be decreased, making them weaker and more susceptible to disease \[[@REF11]\]. Smoking also advances the progression of the disease; it makes it faster due to the decreased supply of blood flow \[[@REF44]\]. The study has also shown that smoking causes DNA methylation, which also leads to cancer formation \[[@REF19],[@REF43]-[@REF44]\]. Patients can present with a wide range of symptoms, the most important being hematuria, abdominal pain, and a mass in the abdominal region. Some other symptoms patients typically present are weight loss, fever, and varicocele \[[@REF19],[@REF44]\]. The treatment for RCC is mainly surgery but can also include radiation therapy. For patients with localized RCC, a partial or total nephrectomy, depending on the stage or spread of cancer, is used \[[@REF19]\]. For patients unable to undergo surgery, radiation is the next considered procedure to best target the small lesions and remove cancer. Patients who have metastasized RCC have a poor prognosis, and treatment usually revolves around targeted therapy and immunotherapy \[[@REF19],[@REF42]\]. Lastly, chemotherapy is also used if cancer has metastasized to other parts of the body outside the kidney \[[@REF19],[@REF42]-[@REF43]\]. Bladder cancer associated with CS Urothelial Cell Carcinoma Urothelial cell carcinoma (UCC) is also called transitional cell carcinoma and is the most common urinary tract cancer that is observed in 90% of cases, most commonly arising from the urothelium of the bladder. The "urothelium\" is made up of a transitional epithelium cell lining, otherwise known as the mucosal surfaces of the renal collecting tubules, calyces and pelvis, and the ureter, bladder, and urethra \[[@REF45]\]. UCC occurs most commonly in the lower urinary tract, the bladder, and the urethra and can also affect the constituents of the upper urinary tract, the renal pelvis of the kidney and the ureter \[[@REF46]\]. An estimated 76,960 new diagnoses of BC have been known to arise in the U.S. in 2016, 16,390 of which would result in the death of the patient. Patients who acquire cancer in the upper portion of the urinary tract typically have a 30% to 50% chance of developing cancer in the bladder, while those with BC have only 2% to 3% chance of developing cancer in the upper urinary tract \[[@REF45]\]. Men acquire cancer of the urothelial tract at a higher rate than women, with a ratio of 3:1, and a peak incidence for both at age 70 \[[@REF45],[@REF47]\]. Whiles acquire UCC at a two times higher rate than African Americans \[[@REF45]-[@REF46]\]. CS is the major cause of UCC \[[@REF12]\]. A strong correlation has been found between cancers of the urothelial tract at all levels, particularly in relation to the duration and amount of cigarette smoke inhaled. Among new BC diagnoses, 90% of cases occur in current or former smokers. Toxicologists have estimated that over 70 confirmed carcinogenic toxins are present within tobacco smoke \[[@REF46]\]. BCs are identified based on how far they invade into the wall of the bladder and are categorized as invasive or non-invasive. Invasive cancers grow into the deeper layers of the bladder wall and are more likely to spread and thus are difficult to treat. Non-invasive cancers remain in the inner layer of the cells, the transitional epithelium, but do not grow into the deeper layers of the bladder wall. Both invasive and non-invasive bladder cancers can be described as superficial, or non-muscle invasive bladder cancer (NMIBC) \[[@REF45],[@REF47]\]. In about 30% of newly diagnosed urothelial bladder tumors, there are multiple sites of bladder involvement, most commonly as carcinomas in situ. A carcinoma in situ that involves the bladder diffusely, without also having a superficial tumor associated with it, is considered an aggressive disease. Most patients manifesting this combination will develop muscle-invasive bladder cancers. However, when carcinoma in situ is associated with superficial tumors, rates of recurrence and disease progression are higher (50% to 80%) than when no such association is present (10%) \[[@REF12]\]. When urothelial tract cancers are staged, superficial BC includes PTs that involve only the mucosa (Ta \[low-grade\]) or submucosa (T1) and flat carcinoma in situ (Tis \[CIS\]). The NMIBC accounts for about 80% of all BCs; Ta BC accounts for most of NMIBC (60%) where T1 and Tis account for 30% and 10%, respectively \[[@REF47]\]. Aside from invasive and non-invasive, BCs are further subdivided into papillary and flat types. Papillary carcinomas (PTCs) are finger-like projections that grow from the inner surface of the bladder towards its hollow center. The PTs often grow towards the center of the bladder, but do not grow into the deeper bladder layers; they are therefore called non-invasive papillary cancers \[[@REF48]\]. When cancer is slow growing, it means that it is very low grade, considered to be a non-invasive papillary carcinoma, and can be called a papillary urothelial neoplasm of low-malignant potential (PUNLMP). This neoplasm tends to have a very good outcome. Flat carcinomas do not grow towards the hollow part of the bladder. If a flat tumor (FT) stays in the inner layer of the bladder cells, it is called a non-invasive flat-carcinoma, or a flat carcinoma in situ (CIS). If a PT or FT grows into the deeper layers of the bladder, then it is called invasive UCC \[[@REF49]\]. Conventional urothelial carcinoma (CUC) is the most common neoplasm that affects the urothelial tract. It may be subdivided into low- and high-grade non-invasive lesions, as well as high-grade invasive carcinomas. Invasive high-grade UCC can progress from either flat urothelial carcinoma in situ (flat CIS), or a non-invasive high-grade papillary urothelial carcinoma by a series of molecular alterations, including smoking, chemical and environmental toxins, etc. By contrast, other papillary urothelial neoplasms rarely progress to high-grade lesions, although they still may recur \[[@REF47]-[@REF50]\]. This subtype of neoplasms includes the following: papillary urothelial neoplasm of low malignancy, non-invasive low-grade papillary UCCs, and papillomas. They are thought to arise from different genetic pathways. This is seen when comparing patients with low-grade papillary neoplasms who have a 15% risk of progression to invasion or flat CIS and patients with high-grade papillary neoplasms who contrastingly have a \>50% risk of progression \[[@REF48]\]. The molecular distinction between low- and high-grade non-invasive urothelial neoplasms, as well as flat CIS, shows a loss of function of a suppressor gene mutation, retinoblastoma 1 (RB1). In high-grade lesions, it is TP53 in which its suppressor function is lost, as well as overexpression of the oncogenes EGFR/Erb-B2 receptor tyrosine kinase 1 (ERBB1) and Erb-B2 receptor tyrosine kinase 2 (ERBB2), and other alterations they exhibit. The changes in the underlying microvasculature are evident at all stages of urothelial carcinogenesis. The following genetic factors mediate changes in microvasculature: vascular endothelial growth factor (VEGF), VEGF receptors, angiopoietins, and thrombospondins. Similar molecular findings found in non-invasive high-grade UCC are also found in invasive UCC, which include alterations in the genes TP53 and phosphatase and tensin homolog (PTEN). Many of the molecular alterations of a variety of tumor suppressor genes/oncogenes and cell adhesion molecules have been examined in both non-invasive and invasive UCC. The molecular alterations to these genes have been described to correlate with an altered prognosis, appearing to hold potential prognostic and therapeutic promise. These include E-cadherin, p53, the RB protein, and the EGFR \[[@REF12],[@REF48]\]. It is estimated that one-third of BC cases could be prevented through simple modification of lifestyle choices, in particular, the cessation of smoking tobacco products (cigarettes, cigars, pipes, etc.) \[[@REF46]\]. The management of UCC depends on these if it is superficial, invasive, and metastatic. The treatment includes resection, radical cystectomy, and chemotherapy. However, even if resected, the risk of recurrence is high \[[@REF12],[@REF46],[@REF48]\]. The prognosis of urethral cancer is poor (five-year survival of ∼ 45%) \[[@REF49]-[@REF50]\]. Conclusions =========== The positive correlation between CS and a handful of carcinomas is predominantly due to tobacco smoke's carcinogenic effect on normal physiology. These carcinogens have been known to lead to DNA damage by impairing the DNA repair mechanism and weakening the immune system, ultimately leading to inflammation and infections. These two pathological consequences of tobacco smoke predispose multiple organs to the development of carcinomas. Although OC and LCs are primarily associated with CS, this study discusses the role in the pathogenesis of additional carcinomas caused by the carcinogens present in the smoke as well. Treatment of the acquired carcinomas is possible by various means depending on the specific carcinoma, although smoking cessation is the most effective means found to prevent the prevalence and incidence of such carcinomas. The authors have declared that no competing interests exist. | Mid | [
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With Halloween approaching, we felt we should warn you about a monster you may not know about. This monster lives off of your most precious resource – time. It’s downright frightening how much of our time can be wasted. See if you can relate to any of these haunting situations: Chatty co-worker You’re working on that bigg project. You reach a point where you just seem stuck. Maybe getting away from your desk will help. So you get up to stretch your legs and grab a cup of coffee. You’re in the break room when that chatty co-worker walks in. Fifteen minutes later, you’re finally back at your desk. You’ve been bitten by Count Clockula! He lives off wasted time, sometimes using other people to feed his ravenous appetite. E-mail alerts You’re busy working at your computer. You see the alert that your friend just sent you an e-mail. You can’t resist. You have to see what it is. It’s a fun video. Well, you might as well watch it now. Wow, it’s funny. Better e-mail your friend. Five minutes later, you’re back to work. Count Clockula got ya again! He sucks your time away by tempting you with things that are appealing. They seem like more fun than the important things you need to work on. Lost keys You’re running late for work. You rush into the kitchen to get a cup of coffee for the road. You grab your laptop bag. Your keys! Where are your keys? You can’t find them anywhere. You look everywhere. Ten minutes later, you find them underneath yesterday’s mail. Count Clockula strikes again! By keeping you from paying attention to seemingly little things, he can suck away a lot of your time. Misplaced files You have a meeting in five minutes and you can’t find the file you need. Where did you put that file? Is it in this stack? No. How about this one? No. You keep looking. If you don’t find it soon, you’ll just have to go without it. Ah, there it is – at the bottom of that overflowing “In” box. Closely related to the last issue, Count Clockula thrives on disorganization. Meetings You went to yet another meeting. The project leader was late. Then he didn’t keep the group on track. The conversation just floated from one issue to another without accomplishing anything. Count Clockula sinks his teeth in again. He thrives on dead time – where groups of people are completely unproductive. Media You have a major report due in a couple of weeks. As you were doing some research for it, you found a great site full of information. You spent a lot of time there. Sure, it was still research, but it was more than you needed for the project. Count Clockula flies again! Sometimes he overwhelms you with his charms. Lack of focus You don’t really have a sense of direction. Sure you think about your goals near the end of every year. But you don’t keep them in front of you like you should. It’s the worst bite Count Clockula can deliver. How can you allocate your most precious resource effectively if you don’t know what you’re trying to accomplish? Word of warning We’d be remiss if we didn’t warn you about one more thing. Unlike other vampires, Count Clockula doesn’t just come out at night – he’s out all the time. Beware! | Low | [
0.5164835164835161,
35.25,
33
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Effect of inositol and phytases on hematological indices and α-1 acid glycoprotein levels in laying hens fed phosphorus-deficient corn-soybean meal-based diets. The effects of feeding low nonphytate phosphorus (NPP) corn-soybean meal-based diets supplemented with myo-inositol at 0.1%, or with phytase B at 1,300 acid phosphatase units/kg, or with phytase B enriched in 6-phytase A at 300 phytase units/kg on the hematological indices and the α-1 acid glycoprotein (AGP) concentrations in the blood of Bovans Brown laying hens were investigated. The experimental design comprised also a negative control diet and an internal control diet that had the NPP content adjusted by the addition of 0.304 g of monocalcium phosphate per kg to reach the NPP level similar to that resulting from the combined action of both phytases. A total of sixty 50-wk-old hens were randomly assigned to the dietary treatments with 12 cage replicates of 1 hen, and fed the experimental diets until wk 62, when the blood samples were taken and analyzed for basic hematological indices and for AGP concentrations in sera. The hematological indices from all the experimental groups remained in a normal range; nevertheless, the statistically significant effects of diet on hemoglobin concentration (P = 0.003), erythrocyte counts (P = 0.035), the percentage of lymphocytes (P = 0.020), heterophils (P = 0.002), eosinophils (P = 0.023), and basophils (P = 0.001) in the leucocyte population, as well as on the heterophil to lymphocyte ratio (P = 0.003), were observed. The highest erythrocyte counts were characteristic for hens fed the diet supplemented with both phytase A and phytase B. The highest heterophil to lymphocyte ratios were found in blood of hens fed the diet supplemented with phytase B, whereas the highest basophil percentages and the highest AGP concentrations occurred in birds fed the negative control diet. A highly significant correlation was observed between AGP concentrations in sera and BW losses determined previously. The results indicate that the low-NPP corn soybean meal-based diets increased acute phase protein level in laying hens. Phytase B alone, and particularly in combination with phytase A, acted as a potent mediator of the response, whereas supplementary myo-inositol did not. | High | [
0.678899082568807,
27.75,
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Q: jquery keeps on selecting element after changing the class I have a button which must change what it does after meeting some condition. So I'm selecting the button by it's class and I want to remove that class upon meeting the condition and add a new class to the element and do something else with it. but it's not working. I just made up an example for my problem. this is the code: $('.button-1').click(function(){ $('.box').width(function(){ return $(this).width() + 10; }); $(this).removeClass('button-1').addClass('button-2'); }); $('.button-2').click(function(){ $('.box').width(function(){ return $(this).width() - 10; }); $(this).removeClass('button-2').addClass('button-1'); }); and it's Fiddle I expect this to toggle between increasing and decreasing the black box width, but it keeps on increasing. A: That's because the event is bound statically on the button, use event delegation like this: $(document).on('click','.button-1', function(){ $('.box').width(function(){ return $(this).width() + 10; }); $(this).removeClass('button-1').addClass('button-2'); }); $(document).on('click','.button-2', function(){ $('.box').width(function(){ return $(this).width() - 10; }); $(this).removeClass('button-2').addClass('button-1'); }); DEMO | Mid | [
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Chemokines in tissue fibrosis. Fibrosis or scarring of diverse organs and tissues is considered as a pathologic consequence of a chronically altered wound healing response which is tightly linked to inflammation and angiogenesis. The recruitment of immune cells, local proliferation of fibroblasts and the consecutive accumulation of extracellular matrix proteins are common pathophysiological hallmarks of tissue fibrosis, irrespective of the organ involved. Chemokines, a family of chemotactic cytokines, appear to be central mediators of the initiation as well as progression of these biological processes. Traditionally chemokines have only been considered to play a critical role in orchestrating the influx of immune cells to sites of tissue injury. However, within the last years, further aspects of chemokine biology including fibroblast activation and angiogenesis have been deciphered in tissue fibrosis of many different organs. Interestingly, certain chemokines appear to mediate common effects in liver, kidney, lung, and skin of various animal models, while others mediate tissue specific effects. These aspects have to be kept in mind when extrapolating data of animal studies to early human trials. Nevertheless, the further understanding of chemokine effects in tissue fibrosis might be an attractive approach for identifying novel therapeutic targets in chronic organ damage associated with high morbidity and mortality. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. | High | [
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362 F.2d 472 Mary Kate UTSEY, as Executrix of the Estate of C. H. Utsey, and C. D. Utsey, Appellants,v.SOUTHERN RAILROAD COMPANY, Appellee. No. 10378. United States Court of Appeals Fourth Circuit. Argued May 31, 1966. Decided June 6, 1966. Arthur G. Howe, Charleston, S. C. (G. M. Howe, Jr., Charleston, S. C., on brief), for appellants. D. W. Robinson, Columbia, S. C., (Ben Scott Whaley, Charleston, S. C., and J. D. Parler, St. George, S. C., on brief), for appellee. Before HAYNSWORTH, Chief Judge, and BOREMAN and J. SPENCER BELL, Circuit Judges. PER CURIAM: 1 In this action for damages allegedly sustained by a lower riparian owner as a result of the defendant's operation of its ponds and its ditching of its forest lands, a jury found a verdict for the defendant. Our consideration of the record in the light of the briefs and oral argument convinces us that there was no fundamental unfairness in the submission of the factual issues, and that the jury's verdict effectively determined them. 2 Affirmed. | Mid | [
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Application Information: AXIN1 antibody, C-term Preliminary experiments gave bands at approx 150kDa and 22-24kDa in Human Brain (Hippocampus) lysates after 0.1µg/ml antibody staining. Please note that currently we cannot find an explanation in the literature for the bands we observe given the calculated size of 95.6kDa according to NP_003493.1 and 91.7kDa according to NP_851393.1. The detected bands were successfully blocked by incubation with the immunizing peptide (and BLAST results with the immunizing peptide sequence did not identify any other proteins to explain the additional bands). We would appreciate any feedback from people in the field - have any results been reported with other antibodies/lysates? Have any further splice variants/modified forms been reported? In paraffin embedded Human Adrenal Gland shows membranous and fibrous staniing in and around secretory cells of the zona fasciculata in the cortex. Recommended concentration, 3-5µg/ml. This antibody is expected to recognise both reported isoforms. Positive Controls The peptide used to product this antibody is available for purchase (Catalog Number:GTX89836-PEP). Form Supplied Liquid Concentration 0.5 mg/ml (Please refer to the vial label for the specific concentration) Purification Purified from goat serum by ammonium sulphate precipitation followed by antigen affinity chromatography using the immunizing peptide. Specifications: AXIN1 antibody, C-term Full Name axin 1 Background Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development. | High | [
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T = Trends for a Stock’s Movement T-Mobile offers mobile communications services under the T-Mobile brands in the United States, Puerto Rico, and the U.S. Virgin Islands. Its service offerings include postpaid and prepaid wireless voice, messaging and data services, mobile broadband, and wholesale wireless services. The merger between Sprint (NYSE:S) and T-Mobile was looking good as the new CEO would have been from the company to be acquired. However that hit a snag when FTC sued T-Mobile recently and it accused the company of adding millions of $ in the form of bogus charges to the bills of subscribers until the last December. CNBC’s Squawk Alley team discussed this and they explained how the bills are being loaded with a lot of additional charges not just by T-Mobile but also a lot of other telecom companies such as Sprint, AT&T (NYSE:T) or Verizon (NYSE:VZ) . “All of us who have looked at a cell phone bill, know that there are all kinds of charges on there that are probably bogus,” Jon Fortt stated. He thinks that the government had a fee for a long time on this which was going nowhere. However, the charges might not impact and hurt T-Mobile specifically as almost every one of the subscribers look at the cell phone bills suspiciously and if the users can quickly respond to this by alerting the authorities with the irregularities this might also bring other telecom companies such as AT&T, Verizon and Sprint into suspicion too which is not very hard and looks feasible. Michael Santoli, Senior columnist at Yahoo! Finance, said that though this charge would act as a counter to the new image of T-Mobile US as being a friend of the cell phone user, it might not change the business proposition of the company. He thinks that the merger might actually create a strong No.3 in the telecom market. Santoli feels that the companies need to be aware of the evolution of the products for the future and they can’t just rely on the present. T = Technicals on the Stock Chart are Mixed T-Mobile stock has struggled to make positive progress over the last couple of months. The is currently trading sideways and may need time to stabilize before heading higher. Analyzing the price trend and its strength can be done using key simple moving averages. What are the key moving averages? The 50-day (pink), 100-day (blue), and 200-day (yellow) simple moving averages. As seen in the daily price chart below, T-Mobile is trading above its rising key averages which signal neutral to bullish price action in the near-term. Source: Thinkorswim Taking a look at the implied volatility (red) and implied volatility skew levels of T-Mobile options may help determine if investors are bullish, neutral, or bearish. Implied Volatility (IV) 30-Day IV Percentile 90-Day IV Percentile T-Mobile options 34.48% 36% 34% What does this mean? This means that investors or traders are buying a minimal amount of call and put options contracts, as compared to the last 30 and 90 trading days. Put IV Skew Call IV Skew August Options Flat Average September Options Flat Average As of today, there is an average demand from call buyers or sellers and low demand by put buyers or high demand by put sellers, all neutral to bullish over the next two months. To summarize, investors are buying a minimal amount of call and put option contracts and are leaning neutral to bullish over the next two months. On the next page, let’s take a look at the earnings and revenue growth rates and the conclusion. | Low | [
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# Copyright (c) 2014, Oracle and/or its affiliates. All rights reserved. # # This program is free software; you can redistribute it and/or modify # it under the terms of the GNU General Public License, version 2.0, # as published by the Free Software Foundation. # # This program is also distributed with certain software (including # but not limited to OpenSSL) that is licensed under separate terms, # as designated in a particular file or component or in included license # documentation. The authors of MySQL hereby grant you an additional # permission to link the program and your derivative works with the # separately licensed software that they have included with MySQL. # # This program is distributed in the hope that it will be useful, # but WITHOUT ANY WARRANTY; without even the implied warranty of # MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the # GNU General Public License, version 2.0, for more details. # # You should have received a copy of the GNU General Public License # along with this program; if not, write to the Free Software # Foundation, Inc., 51 Franklin St, Fifth Floor, Boston, MA 02110-1301 USA # We support MECAB: # - "system" uses headers/libraries in /usr/local/lib # - a custom installation of mecab can be used like this # - cmake -DWITH_MECAB=</path/to/custom/mecab> # # In order to find the .dll files at runtime, you might need to set some # environment variables. # linux: # 'export LD_LIBRARY_PATH=</path/to/custom/mecab>/lib:$LD_LIBRARY_PATH' # windows: # 'set path=</path/to/custom/mecab>\bin;%PATH%' # # If you turn on the option BUNDLE_MECAB, we try to link with the static library. SET(WITH_MECAB_DOC "<empty> (disabled) | system (use os library)") SET(WITH_MECAB_DOC "${WITH_MECAB_DOC} | </path/to/custom/installation> (use custom version)") # Off by default, can be overridden on command line. SET(WITH_MECAB CACHE STRING "${WITH_MECAB_DOC}") # Bundle libmecab with our binaries, if not built from system libs IF(WITH_MECAB STREQUAL "system") OPTION(BUNDLE_MECAB "Bundle mecab and ipadic with plugin" OFF) ELSE() OPTION(BUNDLE_MECAB "Bundle mecab and ipadic with plugin" ON) ENDIF() # MYSQL_CHECK_MECAB # # Provides the following configure options: # WITH_MECAB=[system|<path/to/custom/installation>] FUNCTION (MYSQL_CHECK_MECAB) IF(NOT WITH_MECAB) RETURN() ENDIF() FILE(TO_CMAKE_PATH "${WITH_MECAB}" WITH_MECAB) IF(WIN32) FILE(GLOB WITH_MECAB_HEADER ${WITH_MECAB}/sdk/mecab.h) ELSE() FILE(GLOB WITH_MECAB_HEADER ${WITH_MECAB}/include/mecab.h) ENDIF() IF (WITH_MECAB_HEADER) SET(WITH_MECAB_PATH ${WITH_MECAB} CACHE PATH "path to custom MECAB installation") ENDIF() IF(WITH_MECAB STREQUAL "system" OR WITH_MECAB_PATH) # We reverse the list, in order to prefer .a over .so (or .dylib) IF(BUNDLE_MECAB) LIST(REVERSE CMAKE_FIND_LIBRARY_SUFFIXES) ENDIF() IF(WIN32) FIND_PATH(MECAB_INCLUDE_DIR NAMES mecab.h HINTS ${WITH_MECAB}/sdk ) FIND_LIBRARY(MECAB_LIBRARY NAMES libmecab HINTS ${WITH_MECAB}/sdk ) ELSE() FIND_PATH(MECAB_INCLUDE_DIR NAMES mecab.h HINTS ${WITH_MECAB}/include ) FIND_LIBRARY(MECAB_LIBRARY NAMES mecab HINTS ${WITH_MECAB}/lib ) ENDIF() IF(BUNDLE_MECAB) LIST(REVERSE CMAKE_FIND_LIBRARY_SUFFIXES) ENDIF() IF(MECAB_INCLUDE_DIR AND MECAB_LIBRARY ) SET(MECAB_FOUND TRUE) ELSE() SET(MECAB_FOUND FALSE) ENDIF() MESSAGE(STATUS "MECAB_INCLUDE_DIR = ${MECAB_INCLUDE_DIR}") MESSAGE(STATUS "MECAB_LIBRARY = ${MECAB_LIBRARY}") IF (MECAB_FOUND AND BUNDLE_MECAB) IF(WIN32) FILE(GLOB MECAB_DLL "${WITH_MECAB}/bin/libmecab.dll") FILE(GLOB MECAB_IPADIC "${WITH_MECAB}/dic") IF (MECAB_DLL AND MECAB_IPADIC) INSTALL( FILES "${WITH_MECAB}/bin/libmecab.dll" DESTINATION ${INSTALL_BINDIR} COMPONENT "Server" ) INSTALL( DIRECTORY "${WITH_MECAB}/dic" DESTINATION ${INSTALL_LIBDIR}/mecab USE_SOURCE_PERMISSIONS COMPONENT "Server" ) MESSAGE(STATUS "INSTALL ${WITH_MECAB}/bin/libmecab.dll") MESSAGE(STATUS "INSTALL ${WITH_MECAB}/dic") ELSE() MESSAGE(STATUS "Could not find ${WITH_MECAB}/bin/libmecab.dll or ${WITH_MECAB}/dic") ENDIF() ELSE() GET_FILENAME_COMPONENT(MECAB_LIBRARY_LOCATION "${MECAB_LIBRARY}" PATH) FILE(GLOB MECAB_IPADIC "${MECAB_LIBRARY_LOCATION}/mecab/dic") IF (MECAB_IPADIC) INSTALL( DIRECTORY "${MECAB_LIBRARY_LOCATION}/mecab" DESTINATION ${INSTALL_LIBDIR} USE_SOURCE_PERMISSIONS COMPONENT "Server" ) MESSAGE(STATUS "INSTALL ${MECAB_LIBRARY_LOCATION}/mecab") ELSE() MESSAGE(STATUS "Could not find ${MECAB_LIBRARY_LOCATION}/mecab/dic") ENDIF() ENDIF() # Install mecabrc file. INSTALL( FILES "${CMAKE_SOURCE_DIR}/plugin/fulltext/mecab_parser/mecabrc" DESTINATION "${INSTALL_LIBDIR}/mecab/etc" COMPONENT "Server" ) ENDIF() IF(NOT MECAB_FOUND) UNSET(MECAB_INCLUDE_DIR) UNSET(MECAB_INCLUDE_DIR CACHE) UNSET(MECAB_LIBRARY) UNSET(MECAB_LIBRARY CACHE) MESSAGE(SEND_ERROR "Cannot find appropriate libraries for MECAB. " "WITH_MECAB option are : ${WITH_MECAB_DOC}") ENDIF() ELSE() MESSAGE(SEND_ERROR "Wrong option or path for WITH_MECAB. " "Valid WITH_MECAB options are : ${WITH_MECAB_DOC}") ENDIF() ENDFUNCTION() | Low | [
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"Some Birds Never Return" - but these just might It's a chilly, but beautiful evening and Mary is throwing a party. Everything has to be perfect. Her haven – a house in the middle of nowhere – is deserted as guests are gathering in the garden. Mary's pride and joy is full of red and orange flowers, with tall plants growing freely, just as it should be in nature. Elegant gin glasses are filled to the top and little canapés laid out on the table. But guests don't seem that interested. Rosie, one of the neighbours, likes to cut down trees Mary loves so much. Mrs Fisher won't drink any gin. She loves tea instead. Her husband seems to love anything, but that damn tea. Then there is the boyfriend – Martin. He's well-mannered at first. He's also got a wandering eye. Or is Mary imagining it all? Anything seems possible when the hostess eats Prozac for dinner and downs it with gin. Or when a special artist guest, Kevin, spends six hours driving to the party, his calm presence and aura bewitching the ladies as if Dalai Lama himself had walked in. You're invited – enter at your own risk. “Some Birds Never Return” is a grotesque, but laugh-out-loud play about mental health, abuse, addiction, freedom and different ways of obtaining it. How does one put all of this in a low-budget performance? With the right people. Director and writer, Theodor Spiridon created a perfect, yet disturbing scene by casting actors who seemed to inspire their own roles. His play with language and dark humour gave birth to a balanced script with just enough freedom for the cast to explore their characters, his message to be sent, and unexpected jokes to keep the audience on their toes. As the result, you are gifted an eventful evening with as many hearty laughs as gasps. An evening that can leave you in a state of melancholy and urge to live well. And a huge thirst for gin. We join a neurotic Mary as she obviously struggles with life and her own feelings. Played by Patrycja Dynowska, Mary seems to be the least comfortable person to watch. Her smile rarely fades, as antidepressants and alcohol mute her cry for help and a need to escape from an abusive boyfriend. Sebastian White gives such a convincing performance of a stable host that you might find yourself believing him despite all the evidence that he's the bad guy. Although, he might still be the most normal one. Or is it Rosie, played by Frederica Marilotti who takes over the stage with confidence inserted by her character of a heavy-drinking, smoking and optimistic attitude? With all of these strong performances, it is amazing to see the awkward couple of Mrs and Mr Fisher steal so much of the spotlight. Mimmi Bauer is like a natural light in that depressive garden and even though she only appears for a short time, the audience already shakes with laughter when Mrs Fisher shows up on stage. Playing her husband is Michał Szpak who is as funny as he is tragic. Perfect couple indeed. But this isn't a story about perfect couples and a tea/gin (or as Mrs Fisher invents “tin”) party. There is only so much pretence people can keep up the entire party and the night is getting dark. The last one standing are Mary and Kevin. These two emotional and sensitive characters seem to transform unexpectedly, letting their true natures roam in the night. Patrycja Dynowska and Tim McFarland become a wicked couple who believe to be the only sane people there, about to save humanity by simply getting rid of everyone else. Their performance together makes for a chilly and disturbing ending into how well we can mask our madness behind Dalai Lama references, cocktail dresses, soft words and smiles. They create a world where the spectator feels uncomfortable by Patrycja's evil laugh and Tim's penetrating gaze. By the time this house party ends, you'll be sure to look at things differently, some of them being your neighbour, trees, people closest to you and well, gin and tea. | Mid | [
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Ontario’s best hope of creating a modern, humane social assistance system has expired. Thursday’s provincial budget was its last gasp. Premier Kathleen Wynne wanted to do the right thing. She was prepared to take a political risk for the 850,000 Ontarians struggling to get by on subsistence-level welfare payments. But three months into the job, she realized there was no realistic prospect of “charting a new course on social assistance” as a far-sighted provincial commission proposed. Even the people she aimed to help were balking. So the premier took the safe, conventional route. She made a couple of minor changes to the existing program. They won’t break the bank or ruffle many feathers. In fact, most Ontarians won’t notice them at all. It was exactly the same strategy her predecessor, Dalton McGuinty, had followed. The improvements announced by Finance Minister Charles Sousa in his inaugural budget were fine as far as they went. Social assistance recipients with part-time jobs (about 10 per cent) would get to keep more of their earnings and new applicants would get to keep more of their assets (a car, for instance). But for the majority, little would change. This is the end of the road for anti-poverty activists who fought tenaciously to get the province to overhaul its punitive, rule-bound welfare system. It is a tacit acknowledgement by Wynne that she cannot create the escape route from poverty that she once envisaged. And it is a signal to taxpayers that they can expect to keep pouring billions of dollars into what is essentially a poverty maintenance system. Five days after the budget, there are no complaints. People living on social assistance are relieved the government decided not to scrap the special diet allowance that a quarter of them now receive. People living on disability support are relieved that Wynne jettisoned the idea of merging Ontario Works (general welfare) and the Ontario Disability Support Program. And deficit hawks are relieved that Sousa didn’t raise welfare rates across the board. So who really lost? – The provincial commission that spent two years drafting Brighter Prospects: Transforming Social Assistance , a bold, affordable blueprint to overhaul the system. It turned out to be too bold for the governing Liberals. – Wynne, who aspired to be Ontario’s “ social justice premier .” She had to settle for tinkering with the status quo. – Anyone who believed Ontario had a once-in-generation chance to replace its demeaning hierarchy of handouts with a social assistance system designed to help recipients use whatever abilities they have to support themselves, contribute to society and shed the stigma of dependency. Last week’s budget could have been the seminal step in the journey. – Social assistance recipients themselves — although few recognize it. Wynne was ready to offer them a $100-a-month boost to the lowest welfare rate ($606 per month) plus the two measures in Sousa’s budget. Instead, they lobbied for — and got — a stay of execution for the special diet allowance (which will be whittled back anyway) and a continuation of the two-tier benefit structure put in place by former premier Mike Harris in 1997 so he could slash welfare rates without being accused of punishing the sick and injured. What this means is a continuation of the 1-per-cent rate increases the Liberals have doled out for a decade — Sousa stuck to that pattern — and incremental rule changes if Wynne stays in power. Should Conservative Leader Tim Hudak become premier, rates would be The finance minister tried to portray his changes to social assistance as “far-reaching and fundamental.” A more apt description would have been modest and pragmatic. | Low | [
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DISTRICT COURT OF APPEAL OF THE STATE OF FLORIDA FOURTH DISTRICT MICHAEL TYRONE MOORE, Appellant, v. STATE OF FLORIDA, Appellee. No. 4D18-1083 [ February 5, 2020 ] Appeal from the Circuit Court for the Seventeenth Judicial Circuit, Broward County; Andrew Siegel, Judge; L.T. Case No. 14006988CF10A. Carey Haughwout, Public Defender, and Logan Mohs, Assistant Public Defender, West Palm Beach, for appellant. Ashley Moody, Attorney General, Tallahassee, and Jeanine Germanowicz, Assistant Attorney General, West Palm Beach, for appellee. TAYLOR, J. Appellant, Michael Moore, appeals his conviction and sentence for burglary of a dwelling. Because we conclude that appellant’s confession was involuntary and should have been suppressed, we reverse appellant’s conviction and remand for a new trial. On the morning of May 5, 2014, the victim came home to her apartment and walked into her bedroom. A man jumped out of the bedroom closet, hit her in the head with his hand or an object, and then fled. The intruder appeared to have entered the apartment through the bedroom window. Appellant’s DNA was found on a swab taken from the victim’s bedroom windowsill. Appellant was interrogated for several hours by law enforcement officers. During the interrogation, appellant repeatedly denied that he went inside the victim’s apartment. The officers made multiple comments about helping appellant or speaking to a judge about his case. Some of the officers’ comments could be construed as permissible attempts to confront appellant with evidence of his guilt, such as the following: “So how do we explain to a judge that your DNA is in this lady’s apartment?” However, before appellant confessed, the officers also made multiple vague offers to help appellant, often implying that it would benefit him to “come clean” or that it would be worse for him if he denied culpability. One detective told appellant that “this is the one and only chance you get” if appellant wanted the detective to tell the judge about his cooperation. The detective also suggested that the guys who say things like “I don’t know what you’re talking about” do worse in court. The detective also implied that he had the authority to amend the charges: “So, help me help you, dude . . .. So, help me help you. I [c]an always amend this.” Without quoting the interrogation at length, we note that the officers made constant vague offers to help appellant yet failed to explain or clarify the limits of their authority. About two-and-a-half hours into the interrogation, when a detective asked appellant to tell him “what part of this I have wrong so that, maybe, we can change it,” appellant stated: “Let me talk to you as a man. Fuck all of that I don’t know nothing.” Appellant eventually began to make incriminating statements. Appellant admitted that he had entered the victim’s apartment through the window, but claimed that another man was with him. Appellant stated that when the victim came home, he hid in a hallway closet and left the apartment. Appellant denied hitting the victim and claimed that the other man probably did it. Appellant later made clear that he was implicating himself because he wanted “some form of leniency” and didn’t want to be the guy who says, “I don’t know.” The detective replied: “Well, that’s what I can do for you. That’s why I was telling you – that’s – how I can help you.” The police continued to interrogate appellant for several more hours, questioning him about the May 2014 burglary as well as other burglaries. Appellant moved to suppress the interrogation, but the trial court found that appellant’s confession was voluntary and denied the motion. Appellant’s interrogation was admitted into evidence at trial. The jury found appellant guilty of burglary of a dwelling. Appellant now appeals from his conviction and sentence. On appeal, appellant raises multiple issues, but we need only address 2 appellant’s argument that his confession was involuntary. An appellate court accords a presumption of correctness to the trial court’s factual findings in connection with a motion to suppress, but independently reviews mixed questions of law and fact that ultimately determine constitutional issues. Connor v. State, 803 So. 2d 598, 608 (Fla. 2001). The issue of whether an interrogator’s statements constitute coercion presents a question of law reviewed de novo. State v. Jackson, 120 So. 3d 88, 90–91 (Fla. 4th DCA 2013). Under the due process clause, “[a] confession is inadmissible if it is involuntary.” Martin v. State, 107 So. 3d 281, 298 (Fla. 2012). The determination of whether a confession was voluntary is based on the totality of the circumstances. Arizona v. Fulminante, 499 U.S. 279, 285– 87 (1991). 1 A confession is voluntary if “it was the product of free will and rational choice.” Martin, 107 So. 3d at 298. “Thus, whether a confession is admissible depends on (1) whether the interrogating officers engaged in coercive activity, and (2) whether that activity was sufficient to overcome the free will of the defendant.” Baker v. State, 71 So. 3d 802, 814 (Fla. 2011). “In assessing the totality of the circumstances, a court must consider any promises or misrepresentations made by the interrogating officers.” Martin, 107 So. 3d at 298. “Before finding the confession inadmissible, Florida courts have repeatedly required that the alleged promise ‘induce,’ be ‘in return for,’ or be a ‘quid pro quo’ for the confession.” Blake v. State, 972 So. 2d 839, 844 (Fla. 2007). The absence of an express “quid pro quo” bargain does not, however, preclude a finding of coercion. See Ramirez v. State, 15 So. 3d 852, 856 (Fla. 1st DCA 2009). Although some older Florida cases have stated that police “statements suggesting leniency are only objectionable if they establish an express quid pro quo bargain for confession,” 2 the Florida Supreme Court has since explained that more recent U.S. Supreme Court 1 In Bram v. United States, 168 U.S. 532, 542–43 (1897), the United States Supreme Court stated that a confession cannot be obtained by “any direct or implied promises, however slight.” However, in Arizona v. Fulminate, 499 U.S. 279, 285 (1991), the Court noted that this passage from Bram “does not state the standard for determining the voluntariness of a confession” under current precedent. 2 See State v. Moore, 530 So. 2d 349, 350 (Fla. 2d DCA 1988); see also Bruno v. State, 574 So. 2d 76, 79–80 (Fla. 1991) (citing Moore for this proposition); Philmore v. State, 820 So. 2d 919, 928 (Fla. 2002) (quoting Bruno for this proposition). 3 decisions “render this authority questionable at best.” Martin, 107 So. 3d at 314. Instead, the proper analysis requires an evaluation of the totality of the circumstances. Id. A statement is involuntary if, considering the totality of the circumstances, the court concludes that “the defendant was unable to make a choice free from unrealistic hope and delusions as to his true position, due to the officer’s conduct.” Ramirez, 15 So. 3d at 856. For example, in Ramirez, the First District Court of Appeal held that the defendant’s confession was involuntary where the detective made “constant offers of unspecified help” and failed to explain the limits of his authority, telling the defendant that “[t]his is your only chance” and that “[i]f you want us to help you, you need to help us also.” Id. at 856–57. Similarly, in Day v. State, 29 So. 3d 1178, 1182 (Fla. 4th DCA 2010), our court held that, under the totality of the circumstances, the investigator’s “many offers of help” and statements implying authority to influence the process rendered the defendant’s confession inadmissible as improper “fruits of hope.” Relying on Ramirez, we explained: “The investigator’s constant offers of help, followed by requests for information, and the lack of clarity on the real limits of the investigator’s authority certainly added to appellant’s ‘unrealistic hope’ that the investigator would truly ‘help him.’” Id. Nonetheless, merely advising a suspect of potential penalties and encouraging a suspect to cooperate does not amount to coercive conduct. Martin, 107 So. 3d at 305. Neither does merely offering to make the suspect’s cooperation known to prosecuting authorities or to the judge, without more, render a confession involuntary. See Maqueira v. State, 588 So. 2d 221, 223 (Fla. 1991); Parker v. State, 845 So. 2d 242, 243 (Fla. 5th DCA 2003). In Martin, for example, our supreme court held that a confession was voluntary where, although the detectives offered to convey the defendant’s cooperation to the State, the detectives also explicitly told him that they could not make any promises. 107 So. 3d at 312–13. The supreme court explained that the detectives “clearly explained to [the defendant] the limits of their authority and did not commit an error similar to that in Day or Ramirez.” Id. at 312. However, the supreme court was also careful to note that the techniques the detectives used in Martin presented “the very outer limit as to what tactics law enforcement may employ when performing a custodial interrogation.” Id. at 298. 4 Under the totality of the circumstances in this case, we conclude that appellant’s confession was involuntary. The interrogation tactics in this case were nearly identical to those that resulted in involuntary confessions in Day and Ramirez. Here, just as in Day, the “constant offers of help, followed by requests for information, and the lack of clarity on the real limits of the [officers’] authority certainly added to appellant’s ‘unrealistic hope’ that the [officers] would truly ‘help him.’” 29 So. 3d at 1182. As the State correctly points out, many of the interrogators’ most problematic statements occurred well after appellant had already confessed to key details of the burglary. We thus need not focus on any of the officers’ statements that occurred after appellant began to implicate himself. However, close scrutiny of the officers’ statements that occurred before appellant began to confess leads us to conclude that appellant’s statement was involuntary. Here, as in Day and Ramirez, the officers never explained the limits on their authority to help appellant. The officers gave constant offers of unspecified help when they were requesting information from appellant, told appellant that the interview was his “only chance” to come clean so that they could tell the judge about his cooperation, warned appellant that the guys who say things like “I don’t know what you’re talking about” do worse in court, and even implied significant authority to amend the charges. Viewing the totality of the officers’ statements that led to the confession, we conclude that appellant’s confession was the product of the officers giving appellant an unrealistic hope of leniency and delusions as to his true position. The fact that appellant did not confess to striking the victim is not dispositive on the question of whether his will was overborne. The officers’ tactics clearly induced appellant to make incriminating statements. Their numerous offers of help, suggestions of leniency if appellant cooperated, implied threats of increased punishment if he did not confess, and statements implying authority to influence the process rendered appellant’s confession inadmissible. We cannot say that the erroneous admission of appellant’s confession was harmless. See State v. DiGuilio, 491 So. 2d 1129 (Fla. 1986). Accordingly, we reverse the denial of appellant’s motion to suppress and remand for a new trial. This disposition renders it unnecessary for us to reach the other issues appellant raises on appeal. Reversed and Remanded. 5 MAY and DAMOORGIAN, JJ., concur. * * * Not final until disposition of timely filed motion for rehearing. 6 | Mid | [
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Free Bushnell Weather Station at Wal-mart I just was informed about a great deal at Wal-mart for Bushnell Weather Stations. They are priced at $49.99. Then, there is a rebate for $50.00 – making it FREE AFTER REBATE! The limit is 3 per household, so you could pick up some free birthday or holiday gifts! I'm Tracie! Several years ago, my husband and I found a way to work ourselves out of more than $35,000 in debt. As a result of our journey, we now help families learn to do the same. I share my tips on life, family and finances - to help others achieve this same goal of living a debt free life! Learn more about me and my family HERE. My Latest Videos POPULAR POSTS About Me Tracie is a stay at home mom to three young children; ages 8, 9 and 12. In November 2007, she and her husband decided to eliminate their debt and made many changes in their lifestyle to do just that. She and her husband eradicated over $37,000 in debt in 27 months, through both budgeting and learning how to live a frugal life. She now shares her knowledge in order to help you stretch your hard-earned dollars so you can live the life you want. | Mid | [
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This blog will not focus exclusively on any one State or one part of a State's military. My interests cross national boundaries and are not a reflection of my support for any State. I'd like to think I'm equally critical of the narrative provided by many governments. Expect topics based on the actions of the Russian, American or Canadian armed forces.I am not a conspiracy theorist ; I find the term marginalizing and offensive. I do not believe that lizard people run the shadow government that controls all the world's affairs. I believe there are lots of classified projects and missions the militaries of the world undertake, and don't want to explain in the public eye. Much of what the military says, isn't reflective of what they do. I believe the revelations of Edward Snowden have shown anything is possible with a virtually unlimited budget; so I don't think I'm as much a conspiracy theorist as a realist | Low | [
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The present invention relates in general to logic circuitry, and in particular, to self-timed logic circuitry. Self-timed circuit techniques, once thought only as research-oriented projects, are quickly becoming mainstream in VLSI circuit applications. Requiring no clocks for operation, as does a traditional system, self-timed circuits operate asynchronously on the simple concept of demand. That is, a self-timed circuit operates only when asked to, generates the necessary outputs according to its own internal scheduling, and presents the results to the requester. Afterwards, the circuit xe2x80x9cgoes to sleepxe2x80x9d and awaits the next instruction/request. While asleep, no power is dissipated since no operation is taking place. This is contrary to traditional synchronous systems where even when a circuit is not needed, there is at least power dissipated by the clock circuitry running through the system. This idle power can be significantxe2x80x94studies show that clocking power is approximately 30% of the overall power on a given VLSI circuit/chip. Consequently, self-timed circuits have at least a power advantage over traditional methods. Self-timed circuits also have significant advantages over other techniques such as self-resetting. This approach requires no interaction between driving and receiving circuitry, creating scheduling and arrival time conflicts and complications. FIG. 1 shows an example of a self-timed logic circuit pipeline, or unit 100. Note in FIG. 1 that each block 101-104 labelled xe2x80x9cSelf-timed Logic Circuitxe2x80x9d can, itself, be a combination of self-timed circuits. The operation of such a self-timed system is straightforward and is presented briefly below. Note that this example is an extremely small system. Also, note that each sub-block 101-104 labelled in FIG. 1 as a xe2x80x9cSelf-Timed Logic Circuitxe2x80x9d may, itself, contain multiple self-timed circuit stages and, thus, may also contain operation internally as described below: The input source(s) indicates to the Self-Timed Logical Unit 100 by asserting the xe2x80x9crequestxe2x80x9d signal and enabling the xe2x80x9cdata inputsxe2x80x9d (a bus or multiple of bus signals). Note that the number of such sources is not limited to one, but is only shown as one in FIG. 1 for simplicity. The first (receiving) Self-Timed Logic Circuit xe2x80x9caxe2x80x9d 101 notes that a xe2x80x9crequestxe2x80x9d has been made and returns the xe2x80x9cacknowledgexe2x80x9d signal to the source(s). This signifies to the sources that the information on the xe2x80x9cdata inputsxe2x80x9d has been received. The logic (not shown) that drives the source signals (xe2x80x9cdata inputsxe2x80x9d) is now free to de-assert the xe2x80x9cdata inputsxe2x80x9d, do other operations, etc., since the Self-Timed Logical Circuit xe2x80x9caxe2x80x9d 101 has received the input information and has begun operating. Self-Timed Logic Circuit xe2x80x9caxe2x80x9d 101 operates on the xe2x80x9cdata inputsxe2x80x9d and produces a xe2x80x9cvalid output signalxe2x80x9d to Self-Timed Logic Circuits xe2x80x9cbxe2x80x9d 102 and xe2x80x9ccxe2x80x9d 103 along with xe2x80x9cdata output signalsxe2x80x9d. Circuits xe2x80x9cbxe2x80x9d 102 and xe2x80x9ccxe2x80x9d 103 receive the information and send xe2x80x9ccomplete outxe2x80x9d signals back to circuit xe2x80x9caxe2x80x9d 101 to signify capture of the incoming information. Circuit xe2x80x9caxe2x80x9d 101 is now free to de-assert the output information and, if necessary, receive further inputs from the logical unit input sources. Self-Timed Logic Circuits xe2x80x9cbxe2x80x9d 102 and xe2x80x9ccxe2x80x9d 103 operate on the input information and produce xe2x80x9cvalid output signalsxe2x80x9d and xe2x80x9cdata output signalsxe2x80x9d, which are then sent to Self-Timed Logic Circuit xe2x80x9cdxe2x80x9d 104. Circuit xe2x80x9cdxe2x80x9d 104 awaits for both xe2x80x9cvalid signalsxe2x80x9d to arrive, then returns a xe2x80x9ccomplete outxe2x80x9d signal back to both circuits xe2x80x9cbxe2x80x9d 102 and xe2x80x9ccxe2x80x9d 103. Circuits xe2x80x9cbxe2x80x9d 102 and xe2x80x9ccxe2x80x9d 103 are now able to de-assert their respective outputs and receive further information as necessary from circuit xe2x80x9caxe2x80x9d 101. Self-Timed Logic Circuit xe2x80x9cdxe2x80x9d 104 operates on the information and produces a xe2x80x9cvalid output signalxe2x80x9d and xe2x80x9cdata output signalsxe2x80x9d to the external sink (not shown) in the overall chip system. Note that sinks (not shown) may be single or multiple, depending on the particular architecture and placement of a self-timed logical unit. When, the receiving units (sinks) signify that the information has been received (via xe2x80x9ccompletion signals from sinksxe2x80x9d) the Self-Timed Logic Circuit xe2x80x9cdxe2x80x9d 104 may de-assert its outputs and receive further information from circuits xe2x80x9cbxe2x80x9d 102 and xe2x80x9ccxe2x80x9d 103. To control this operation, please refer to U.S. Pat. Nos. 5,565,798 and 5,708,374, which are hereby incorporated by reference herein. As a result of this operation, it can be seen that in the general self-timed case, no registers are required. That is, in a completely self-timed system, the combination of valid/complete cycles removes the necessity of synchronization of internal units and sub-blocks as the units, in reality, time and clock themselves. Thus, self-timed circuits and systems synchronize themselves. Therefore, in the limit, a completely self-timed microprocessor, for example, would require no on-chip or off-chip clocks. However, most self-timed circuitry is dynamic. As such, it is prone to errors created by noise events, as are all dynamic circuits, and, additionally, must distribute the self-timing clocks to every circuit. For example, consider the circuits of FIGS. 2A, 2B, and 2C, which were described in U.S. Pat. Nos. 5,565,798 and 5,708,374. (Some signals are not shown in FIG. 2A to reduce complexity and increase understanding of the present invention.) In this circuitry, each xe2x80x9cDomino Logic Rowxe2x80x9d of the xe2x80x9cSelf-Timed Macro Dataflowxe2x80x9d in FIG. 2C receives a clock signal (xe2x80x9cStrobexe2x80x9d or xe2x80x9cResetxe2x80x9d) from the control circuit in FIG. 2B. Note that each xe2x80x9cDomino Logic Rowxe2x80x9d is constructed of a collection of domino circuits. One drawback of such a system is in the use of the dynamic circuits for all functions. That is, dynamic circuits are susceptible to noise events, which cause them to evaluate improperly and from which they cannot recover; they require a clock signal to be routed to each circuit, which increases the design complexity and the chip clocking loading; they create more on-chip noise due to precharge/evaluate events, fast edge rates, and the multitude of clock signals (noise coupling to adjacent lines); they cause test problems, particularly at elevated temperatures and voltages, much of which is necessary for reliability and screening; and they must wait upon the clock signal in order to start the evaluation process, which makes them susceptible to clock skew problems. Static circuits, on the other hand, do not suffer from many of these issues: they can always recover from an incorrect evaluation, given enough time, and, consequently and importantly, a correct state can always be gained by waiting; they require no clock signals, which reduces the design complexity and global chip clock loading; they tend to reduce the overall chip noise as the precharge/evaluate nature is removed and the clock signals are not required; they are xe2x80x9cfriendlyxe2x80x9d to test at elevated temperatures and voltages as functionality is nearly always guaranteed; and they do not need to wait upon a clock signal for evaluation as one is not required. Also, they typically dissipate less power than their dynamic counterparts, mainly due to the removal of the clock signal to each circuit, which requires a switching clock signal every cycle regardless of the switching activity of the dynamic circuit. Examples of static circuits are illustrated in FIGS. 11A and 11B. An important key, however, is performance. Dynamic circuits, with all their hazards and complications, consistently outperform static circuits in terms of delay. This means that critical circuit paths tend to be dynamic to produce the fastest chip possible, while non-critical circuit paths tend to be static to reduce power and design hazard as the performance is not critical (the chip (clock) speed is always set speed by the slowest possible path). In typical clock systems, this is not an issue as the latch boundaries separate the circuit styles, permitting static and dynamic circuits to coexist. This means, generally, that static and dynamic circuits can, effectively, be swapped in for one another without concern (the swapping can, obviously, change the delay and, thus, the critical path of the overall chip). However, in a self-timed system, the use of static circuits is not as simple. For instance, consider the circuitry of FIG. 2C replaced with static circuitry (i.e., each xe2x80x9cDomino Logic Rowxe2x80x9d is replaced with a xe2x80x9cStatic Logic Rowxe2x80x9d). When the inputs (l through p) arrive, the circuitry of the first row begins to evaluate, regardless of the valid input signals. Similarly, the subsequent rows of the logic evaluate, ultimately producing the xe2x80x9cData Outputxe2x80x9d signals without regard to the valid and complete signals. The net result is that the interlocking concept created by the use of the dynamic circuits is lost when those circuits are replaced with static circuits. Consequently, the use of static circuits in such a system is nearly precluded. The present invention addresses the foregoing limitations by providing a new self-timed circuitry system wherein static circuits can be used in a CMOS self-timed system. As a result, the benefits of static logic can be attained. In one embodiment, the present invention is a self-timed logic circuit having a first transparent latch register for receiving one or more input data signals from one or more sources. The self-timed logic circuit also includes a control circuit operable for receiving one or more valid signals corresponding to each of the input data signals. A combinatorial static logic block then receives the one or more input data signals from the transparent latch register and performs one or more functions on the input data signals as a result of the static logic circuits within the logic block. A second transparent latch register then receives the output from the combinatorial static logic block. The control circuit will output the output data signals through the second transparent latch register to one or more sink circuits. The foregoing has outlined rather broadly the features and technical advantages of the present invention in order that the detailed description of the invention that follows may be better understood. Additional features and advantages of the invention will be described hereinafter which form the subject of the claims of the invention. | Mid | [
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--- abstract: | To any algebraic curve $A$ in ${({\mathbb C}^*)^2}$ one may associate a closed infinite region ${\mathcal{A}}$ in ${\mathbb R}^2$ called [*the amoeba*]{} of $A$. The amoebas of different curves of the same degree come in different shapes and sizes. All amoebas in ${({\mathbb R}^*)^2}$ have finite area and, furthermore, there is an upper bound on the area in terms of the degree of the curve. The subject of this paper is the curves in ${({\mathbb C}^*)^2}$ whose amoebas are of the maximal area. We show that up to multiplication by a constant in ${({\mathbb C}^*)^2}$ such curves are defined over ${\mathbb R}$ and, furthermore, that their real loci are isotopic to so-called [*Harnack curves*]{}. author: - | Grigory Mikhalkin [^1]\ Department of Mathematics\ University of Utah\ Salt Lake City, UT 84112, USA\ [email protected] - | Hans Rullg[å]{}rd\ Department of Mathematics\ Stockholm University\ S-10691 Stockholm, Sweden\ [email protected] title: 'Amoebas of maximal area.' --- Introduction. ============= Let $f:{\mathbb C}^2\to{\mathbb C}$ be a polynomial, $f(z_1,z_2)=\sum\limits_{j,k} a_{jk}z_1^jz_2^k$. Its zero set in ${({\mathbb C}^*)^2}$ is a curve $A=f^{-1}(0)\cap{({\mathbb C}^*)^2}$ (where ${\mathbb C}^*={\mathbb C}{\smallsetminus}\{0\}$). Let $\Delta\subset{\mathbb R}^2$ be the Newton polygon of $f$, i.e. the convex hull of $\{(j,k)\ |\ a_{jk}\neq0\}$. Gelfand, Kapranov and Zelevinski introduced one more object associated to $f$. [^2] The amoeba ${\mathcal{A}}\subset{\mathbb R}^2$ of $f$ is ${\operatorname{Log}}(A)$, where ${\operatorname{Log}}:{({\mathbb C}^*)^2}\to{\mathbb R}^2$, $(z_1,z_2)\mapsto(\log|z_1|,\log|z_2|)$. It was remarked in [@GKZ] that every component of ${\mathbb R}^2{\smallsetminus}{\mathcal{A}}$ is open and convex in ${\mathbb R}^2$. In particular, ${\mathcal{A}}$ is closed and its (Lebesgue) area is well-defined. Note that ${\mathcal{A}}$ is never bounded in ${\mathbb R}^2$, since $f^{-1}(0)$ must intersect the coordinate axes in ${\mathbb C}^2$. However it was shown by Passare and Rullg[å]{}rd [@PaRu] that the area of ${\mathcal{A}}$ is always finite. Furthermore, it is bounded in terms of $\Delta$. $$\label{areaineq} {\operatorname{Area}}({\mathcal{A}})\le\pi^2{\operatorname{Area}}(\Delta).$$ The main result of this paper is the extremal property of this inequality. We say that a curve $A$ is defined over ${\mathbb R}$ if it is invariant under the complex conjugation ${\operatorname{conj}}:{({\mathbb C}^*)^2}\to{({\mathbb C}^*)^2}$, $(z_1,z_2)\mapsto (\bar{z}_1,\bar{z}_2)$. In this case we may consider the real part of the curve ${\mathbb R}A=A\cap({\mathbb R}^*)^2$ which is a real algebraic curve. We say that a curve $A$ is real up to multiplication by a constant if there exist constants $b_1,b_2\in{\mathbb C}^*$ such that $(b_1,b_2)\times A\subset{({\mathbb C}^*)^2}$ is defined over ${\mathbb R}$. The condition that $A$ is real up to multiplication by a constant is equivalent to the condition that there exist $a,b_1,b_2\in{\mathbb C}^*$ such that the polynomial $af(\frac{z_1}{b_1}, \frac{z_2}{b_2})$ has real coefficients. In this case we may also consider the real part ${\mathbb R}A=\{(x_1,x_2)\in{({\mathbb R}^*)^2}\ |\ af(\frac{x_1}{b_1},\frac{x_2}{b_2})=0\}$. We say that a map is at most 2-1 if the inverse image of any point in the target consists of at most 2 points. The main result of this paper is the following theorem. \[main\] Suppose that ${\operatorname{Area}}(\Delta)>0$. Then the following conditions are equivalent. 1. ${\operatorname{Area}}({\mathcal{A}})=\pi^2{\operatorname{Area}}(\Delta).$ 2. The map ${\operatorname{Log}}|_A: A\to{\mathbb R}^2$ is at most 2-1 and $A$ is real up to multiplication by a constant. 3. The curve $A$ is real up to multiplication by a constant and its real part ${\mathbb R}A$ is a (possibly singular) Harnack curve (see Definitions \[ha\] and \[sha\]) for the Newton polygon $\Delta$. Furthermore, these conditions imply that the non-singular locus of ${\mathbb R}A$ coincides with $A\cap{\operatorname{Log}}^{-1}({\partial}{\mathcal{A}})$. The inequality is sharp for any Newton polygon $\Delta$. The corollary follows from Theorem \[main\] and the Harnack-Itenberg-Viro Theorem (see section \[harnackcurves\]) on existence of Harnack curves. A curve that is real up to multiplication by a constant may have more than one real part (other real parts may come as a result of multiplication by different constants). For instance, if $f$ is a real polynomial which contains only even powers of $z_2$ then the pullback of $f$ under $(z_1,z_2)\mapsto (z_1,iz_2)$ is a real polynomial with a different real part. The theorem implies that a Harnack curve is real up to multiplication by a constant in a unique way. Indeed, the choice of the real part is determined by the identity ${\mathbb R}A=A\cap{\operatorname{Log}}^{-1}({\partial}{\mathcal{A}})$. Harnack curves in ${({\mathbb R}^*)^2}$. {#harnackcurves} ======================================== Let us fix a convex polygon $\Delta\subset{\mathbb R}^2$ whose vertices have integer coordinates. Consider all possible real polynomials $f$ whose Newton polygon is $\Delta$. The same polynomial $f$ may be viewed both as a function ${({\mathbb C}^*)^2}\to{\mathbb C}$ and as a function ${({\mathbb R}^*)^2}\to{\mathbb R}$. Let ${\mathbb R}A$ be the zero set of $f$ in ${({\mathbb R}^*)^2}$. Equivalently, ${\mathbb R}A$ is a real part of the zero set $A$ of $f$ in ${({\mathbb C}^*)^2}$. For a generic choice of coefficients of $f$ the curve ${\mathbb R}A$ is smooth. However the topology of $(({\mathbb R}^*)^2,{\mathbb R}A)$ is different for different choices of coefficients of $f$. In particular, the number of components of ${\mathbb R}A$ may be different. Also the mutual position of the components may be different. We may compactify the above setup. Recall (see e.g. [@GKZ]) that the polygon $\Delta$ determines a toric surface ${\mathbb C}T_\Delta\supset{({\mathbb C}^*)^2}$. We denote the real part of ${\mathbb C}T_\Delta$ with ${\mathbb R}T_\Delta\supset{({\mathbb R}^*)^2}$. The surface ${\mathbb C}T_\Delta$ is a compactification of ${({\mathbb C}^*)^2}$. Furthermore, the complement ${\mathbb C}T_\Delta{\smallsetminus}{({\mathbb C}^*)^2}$ is a union of $n$ (non-disjoint) lines, where $n$ is the number of sides of $\Delta$. Similarly, ${\mathbb R}T_\Delta{\smallsetminus}{({\mathbb R}^*)^2}$ is a union of $n$ real lines $l_1,\dots,l_n$. These lines are called the [*axes*]{} of ${\mathbb R}T_\Delta$. We assume that the indexing of $l_k$ is consistent with the natural cyclic order on the sides of $\Delta$. The closure $\bar{A}$ of $A\subset{({\mathbb C}^*)^2}\subset{\mathbb C}T_\Delta$ in ${\mathbb C}T_\Delta$ is a compact curve whose real part is ${\mathbb R}\bar{A}\supset{\mathbb R}A$. The topology of the triad $({\mathbb R}T_\Delta;{\mathbb R}\bar{A},l_1,\cup\dots\cup l_n)$ carries all topological information on arrangement of ${\mathbb R}A$ in ${({\mathbb R}^*)^2}$. The upper bound on the number of components of ${\mathbb R}\bar{A}\subset {\mathbb R}T_\Delta$ is provided by Harnack’s inequality [@Ha]. This number is never greater than one plus the genus of $A$. Recall that by [@Kh] the genus of $A$ is equal to the number of lattice points in the interior of $\Delta$. We denote this number with $g$. To deduce the upper bound on the number of components of ${\mathbb R}A\subset{({\mathbb R}^*)^2}$ we recall that ${\mathbb R}A={\mathbb R}\bar{A}{\smallsetminus}(l_1\cup\dots \cup l_n)$, where $l_k$ corresponds to a side $\delta_k$ of $\Delta$. Let $d_k$ be the integer length of $\delta_k$, i.e. the number of lattice points inside $\delta_k$ plus one. Note that this length is an $SL(2,{\mathbb Z})$-invariant. The curve ${\mathbb R}\bar{A}$ and the axis $l_k$ intersect in no more that $d_k$ points, since $d_k$ is the intersection number of their complexifications. Therefore, ${\mathbb R}A$ has no more than $g+\sum\limits_{k=1}^n d_k$ components. \[ha\] A non-singular curve ${\mathbb R}A\subset{({\mathbb R}^*)^2}$ with the Newton polygon $\Delta$ is called a [*Harnack curve*]{} if all the following conditions hold. - The number of components of ${\mathbb R}\bar{A}$ is equal to $g+1$ (where $g$ is the number of lattice points in the interior of $\Delta$). - All components of ${\mathbb R}\bar{A}$ but one do not intersect $l_1\cup\dots\cup l_n$. - A component $C$ of ${\mathbb R}\bar{A}$ can be divided into $n$ consecutive (with respect to the cyclic order on $C$) arcs $\alpha_1,\dots,\alpha_n$ so that for each $k$ the intersections $\alpha_k\cap l_k$ consists of $d_k$ points, while $\alpha_k\cap l_j=\emptyset$, $j\neq k$. Note that the first two conditions imply that the number of components of a Harnack curve ${\mathbb R}A$ is equal to $g+\sum\limits_{k=1}^n d_k$. For each Newton polygon $\Delta$ the topological type of the triad $({\mathbb R}T_\Delta;{\mathbb R}\bar{A},l_1\cup\dots\cup l_n)$ is unique if ${\mathbb R}A$ is a Harnack curve. Note that the above theorem implies that the topological type of the pair $({({\mathbb R}^*)^2}, {\mathbb R}A)$ is also unique for each $\Delta$. Harnack curves exist for any Newton polygon $\Delta$. Harnack [@Ha] proved this theorem for plane projective curves of arbitrary degree $d$. In our language this corresponds to the case when $\Delta$ is a triangle whose vertices are $(0,0)$, $(d,0)$, $(0,d)$. Harnack’s example was generalized to arbitrary Newton polyhedra $\Delta$ with the help of Viro’s patchworking described in [@IV], see Corollary A4 in [@Mi]. The Harnack curves are a special case of the so-called T-curves, see [@IV]. We refer to [@IV] and [@Mi] for illustrations of Harnack curves. Recall that a point $p\in{\mathbb R}A\subset{({\mathbb R}^*)^2}$ is called an [ordinary real isolated double point]{} of ${\mathbb R}A$ (or an $\operatorname{A_1^+}$-point, see [@AVGZ]) if there exist local coordinates $x_1,x_2$ at $p\subset{({\mathbb R}^*)^2}$ such that $A$ is locally defined by equation $x_1^2+x_2^2=0$. \[sha\] A singular curve ${\mathbb R}A\subset{({\mathbb R}^*)^2}$ with the Newton polygon $\Delta$ is called a singular [*Harnack curve*]{} if - the only singular points of ${\mathbb R}A$ are $A_1^+$-points (ordinary real isolated double points); - the result of replacing of the singular points of ${\mathbb R}A$ with small ovals (which corresponds to replacing with the locus $x_1^2+x_2^2=\epsilon, \epsilon>0$ in the local coordinates) gives a Harnack curve for $\Delta$. In other words, a singular Harnack curve is the result of contraction to points of some ovals of a non-singular Harnack curve. Monge-Ampère measure on ${\mathcal{A}}$. {#hans} ======================================== In the next section we prove the equivalence of conditions 1 and 2 in the main theorem. The proof is an extension of the proof of the inequality given in [@PaRu]. We recapture in this section the main points in this proof. The idea is to construct a measure on the amoeba ${\mathcal{A}}$, whose total mass is related to $\Delta$ and which can be computed explicitly in terms of the hypersurface $A$. This measure will be obtained as the real Monge-Ampère measure of a certain convex function associated to $f$. We indicate briefly the definition of the real Monge-Ampère operator. Details may be found in [@RaTa]. Suppose $u$ is a smooth convex function defined in ${\mathbb R}^n$. Then ${\operatorname{grad}}u$ defines a mapping from ${\mathbb R}^n$ to ${\mathbb R}^n$. The Monge-Ampère measure ${\operatorname{M}}u$ of $u$ is defined by ${\operatorname{M}}u(E) = \lambda({\operatorname{grad}}u(E))$ for any Borel set $E$, where $\lambda$ denotes Lebesgue measure on ${\mathbb R}^n$. That this is actually a measure requires a proof, since ${\operatorname{grad}}u$ is in general not 1-to-1. If $u$ is convex but not necessarily smooth, ${\operatorname{grad}}u$ can still be defined as a multifunction, and the Monge-Ampère measure of $u$ is defined as in the smooth case. For smooth functions the Monge-Ampère measure is given by the determinant of the Hessian matrix, $$\mu=|{\operatorname{Hess}}(u)|\lambda,$$ where $\lambda$ is the Lebesgue measure. #### Suppose now that $f$ is a given polynomial in two variables and define $$N_f(x) = \frac{1}{(2\pi i)^2} \int_{{\operatorname{Log}}^{-1}(x)} \frac{\log|f(z)|\, dz_1\, dz_2}{z_1 z_2}.$$ This is a real-valued function defined in ${\mathbb R}^2$, which is convex because $\log|f(z)|$ is plurisubharmonic. Define $\mu$ to be the Monge-Ampère measure of $N_f$. \[lem1\] The measure $\mu$ has its support in ${\mathcal{A}}$ and its total mass is equal to the area of $\Delta$. It is not difficult to show that $N_f$ is affine linear in each connected component of ${\mathbb R}^2 \smallsetminus {\mathcal{A}}$ and that the gradient image ${\operatorname{grad}}N_f ({\mathbb R}^2)$ is equal to $\Delta$ minus some of its boundary points. This readily implies the statement. For details we refer to [@PaRu]. #### Let $F$ denote the set of critical values of the mapping ${\operatorname{Log}}: A \to {\mathbb R}^2$. Pick a point $x_0 \in {\mathcal{A}}\smallsetminus F$ and functions $\phi_{j}, \psi_{j}$ defined in a neighborhood $V$ of $x_{0}$, where $j$ ranges from 1 to $n$ and $n$ is the cardinality of ${\operatorname{Log}}^{-1}(x_0) \cap A$, such that $A \cap {\operatorname{Log}}^{-1}(V) = \cup_{j = 1}^n \{(\exp(x_{1} + i\phi_{j}(x)), \exp(x_{2} + i\psi_{j}(x)));x = (x_{1},x_{2}) \in V\}$. The main step in the proof of the inequality is the following computation. \[lem2\] With notations as above we have $$\label{hessian} {\operatorname{Hess}}(N_{f}) = \frac{1}{2\pi} \sum_{j=1}^n \pm \begin{pmatrix}\partial \psi_{j}/\partial x_{1} & \partial \psi_{j}/\partial x_{2}\\ -\partial \phi_{j}/\partial x_{1} & -\partial \phi_{j}/\partial x_{2} \end{pmatrix}.$$ The signs depend on the signs of the intersection numbers between ${\operatorname{Log}}^{-1}(x_0)$ and $A$. Each term in the sum is a symmetric, positive definite matrix with determinant equal to 1. #### For the proof we refer to [@PaRu]. We remark that the fact that the matrices are symmetric with determinant equal to 1 follows immediately when we know that $A$ is a complex analytic curve. The two last lemmas immediately imply the inequality via the following corollary. \[cor1\] If $\lambda$ denotes Lebesgue measure in ${\mathbb R}^2$, then $\mu \geq (\lambda/\pi^2)|_{{\mathcal{A}}}$. Hence the area of ${\mathcal{A}}$ is not greater than $\pi^2$ times the area of $\Delta$. It is not difficult to show that for $2 \times 2$ symmetric, positive definite matrices $M_1, M_2$ the inequality $$\label{detineq} \sqrt{\det(M_1 + M_2)} \geq \sqrt{\det M_1} + \sqrt{\det M_2}$$ holds, with equality precisely if $M_1$ and $M_2$ are real multiples of each other. Applying this to the sum and using the fact that it contains at least two terms for all $x_0 \in {\mathcal{A}}\smallsetminus F$, the first statement follows. Combining this with Lemma \[lem1\] yields the second part. The inequality used in the previous proof follows as a special case of an inequality for positive definite matrices of arbitrary size, analogous to the Alexandrov-Fenchel inequality for mixed volumes. The general inequality can be found in [@Al]. Proof of Theorem 1: conditions 1 and 2 are equivalent. ====================================================== #### We are now ready to prove the equivalence of conditions 1 and 2. Note that by Corollary \[cor1\], ${\operatorname{Area}}({\mathcal{A}}) = \pi^2 {\operatorname{Area}}(\Delta)$ if and only if $\mu = (\lambda/\pi^2)|_{{\mathcal{A}}}$. Implication $1 \implies 2$. --------------------------- Suppose that $\mu = (\lambda/\pi^2)|_{{\mathcal{A}}}$. We first show that $f$ is irreducible. \[irreducible\] If $\mu = (\lambda/\pi^2)|_{{\mathcal{A}}}$, then $f$ is irreducible. Let $K, L$ be compact convex subsets of ${\mathbb R}^2$. From the monotonicity properties of mixed volumes it follows that ${\operatorname{Area}}(K + L) \geq {\operatorname{Area}}(K) + {\operatorname{Area}}(L)$ with strict inequality holding unless one of $K, L$ is a point or $K$ and $L$ are two parallel segments. Assume now that we have a non-trivial factorization $f = gh$ and let $\Delta_g, \Delta_h$ denote the Newton polytopes and ${\mathcal{A}}_g, {\mathcal{A}}_h$ the amoebas of $g$ and $h$ respectively. From Lemma \[lem1\] it follows that ${\operatorname{Area}}({\mathcal{A}}) = \pi^2 {\operatorname{Area}}(\Delta)$. On the other hand, since ${\mathcal{A}}= {\mathcal{A}}_g \cup {\mathcal{A}}_h$ and $\Delta = \Delta_g + \Delta_h$, it follows from Corollary \[cor1\] that $${\operatorname{Area}}({\mathcal{A}}) \leq {\operatorname{Area}}({\mathcal{A}}_g) + {\operatorname{Area}}({\mathcal{A}}_h) \leq \pi^2({\operatorname{Area}}(\Delta_g) + {\operatorname{Area}}(\Delta_h)) < \pi^2 {\operatorname{Area}}(\Delta).$$ This is a contradiction. From it follows that for equality to hold in Corollary \[cor1\] it is necessary that ${\operatorname{Log}}^{-1}(x)$ intersects $A$ in at most two points for all $x \not \in F$. Hence the sum contains two terms with opposite signs. For equality to hold in applied to the sum it is necessary that ${\operatorname{grad}}\phi_1 = - {\operatorname{grad}}\phi_2$ and ${\operatorname{grad}}\psi_1 = - {\operatorname{grad}}\psi_2$. After a multiplication of each coordinate by a constant we may assume that $\phi_1 = - \phi_2, \psi_1 = - \psi_2$ in a neighborhood of a given point in ${\mathcal{A}}\smallsetminus F$. (The existence of such points is guaranteed by the assumption that ${\operatorname{Area}}(\Delta)$ and hence ${\operatorname{Area}}({\mathcal{A}})$ is positive.) But then $f(z)$ and $\overline{f(\bar{z})}$ have a common factor, and hence coincide up to a multiplicative constant since they are irreducible. Multiplying $f$ by a suitable constant, we obtain a polynomial with real coefficients. To complete the proof we must show that ${\operatorname{Log}}^{-1}(x_{0})$ intersects $A$ in at most two points for all $x_0 \in F$. Note that ${\operatorname{Log}}^{-1}(x_0)\cap A$ cannot contain more than 2 isolated points. Indeed, a small neighborhood in $A$ of an isolated point in ${\operatorname{Log}}^{-1}(x_0)\cap A$ is mapped by ${\operatorname{Log}}$ either onto a neighborhood of $x_{0}$, or in a 2-to-1 fashion onto a half-disk with $x_{0}$ on its boundary. In any case, the presence of more than 2 isolated points would imply that ${\operatorname{Log}}^{-1}(x)\cap A$ contains more than two points for some $x\notin F$, which is a contradiction. If ${\operatorname{Log}}^{-1}(x_0) \cap f^{-1}(0)$ contains a curve $\gamma$ we consider two different cases. If $\gamma$ is of the form ${\operatorname{Log}}^{-1}(x_0) \cap \{z_1^jz_2^k = c\}$ for some $(j,k) \in {\mathbb Z}^2$ and $c \in {\mathbb C}$, then $f$ contains the factor $z_1^jz_2^k - c$, which is impossible by Lemma \[irreducible\]. Otherwise, $t \gamma := \{(t_1 z_1, t_2 z_2); (z_1,z_2) \in \gamma\}$ intersects $\gamma$ for all $t$ in an open set in the real torus ${\mathbf{T}}^2$. By Theorem 5 in [@PaRu] (cf. the proof of Lemma \[lem3\]) this implies that $\mu$ has a point mass at $x_0$, contradicting the assumptions. Hence we have shown that ${\operatorname{Log}}: A \to {\mathbb R}^2$ is at most 2-to-1. Implication $2 \implies 1$. --------------------------- Conversely, assume that ${\operatorname{Log}}:A \to {\mathbb R}^2$ is at most 2-to-1 and that $f$ has real coefficients. Since ${\mathcal{A}}$ and $\mu$ are invariant under the changes of variables permitted in the theorem, this is no loss of generality. Then the sum has two terms. Since $A$ is invariant under complex conjugation of the variables, it follows that $\phi_{1} = - \phi_{2}, \psi_{1} = - \psi_{2}$, hence the two terms are actually equal. This shows immediately that $\mu = (\lambda/\pi^2)|_{{\mathcal{A}}}$ outside $F$. By the following Lemma neither $\mu$ nor $\lambda$ has any mass on $F$, so this equality holds everywhere. \[lem3\] If ${\operatorname{Log}}^{-1}(x) \cap A$ is a finite set for all $x$, then $\mu$ has no mass on $F$. In Theorem 5 in [@PaRu] it is shown that $\mu(E)$ is proportional to the average number of solutions in ${\operatorname{Log}}^{-1}(E)$ to the system of equations $$\label{eq2} f(z_1, z_2) = f(t_1 z_1, t_2 z_2) = 0$$ as $(t_1, t_2)$ ranges over the real torus ${\mathbf{T}}^2 = \{t \in {\mathbb C}^2; |t_1| = |t_2| = 1\}$. Note that the set of critical values of the mapping $A \to {\mathbb R}^2 : (z_1, z_2) \mapsto (|z_1|^2, |z_2|^2)$ is a semialgebraic set. Thus it is contained in a real-algebraic curve $\tilde{F}$. Consider the product space ${\mathbb C}^2 \times {\mathbf{T}}^2$ with the two projections $\pi_1$ and $\pi_2$ onto ${\mathbb R}^2$ and ${\mathbf{T}}^2$ defined by $\pi_1(z,t) = (|z_1|^2, |z_2|^2)$ and $\pi_2(z,t) = t$. Let $C = \pi_1^{-1}(\tilde{F}) \cap \{f(z_1, z_2) = f(t_1 z_1, t_2 z_2) = 0\} \subset {\mathbb C}^2 \times {\mathbf{T}}^2$. Since the map $ \pi_1 : C \to \tilde{F}$ has discrete fibers, it follows that $C$ is a real curve. Hence $\pi_2(C)$ is a null set in ${\mathbf{T}}^2$. Since the equation has no solutions in ${\operatorname{Log}}^{-1}(F)$ for $t$ outside $\pi_2(C)$, it follows that $\mu(F) = 0$ as required. Proof of Theorem \[main\]: conditions 2 and 3 are equivalent. ============================================================= Implication $2\implies 3$. -------------------------- By our assumption $A$ is real up to multiplication by a constant. Thus multiplying by a suitable constant we may assume that $A$ is already defined over ${\mathbb R}$. In this case we may define the real part ${\mathbb R}A$ as the fixed point set of the involution of complex conjugation ${\operatorname{conj}}:(z_1,z_2)\mapsto (\bar{z_1},\bar{z_2})$ restricted to $A$. Let $\nu:\tilde{A}\to A$ be the normalization of the curve $A$. The involution ${\operatorname{conj}}|_A$ can be lifted to an involution ${\operatorname{conj}}_{\tilde{A}}$ on the Riemann surface $\tilde{A}$. Let ${\mathbb R}\tilde{A}$ be the real part of $\tilde{A}$. Note that $\nu({\mathbb R}\tilde{A})\subset{\mathbb R}A$, but real isolated (singular) points of ${\mathbb R}A$ are not contained in $\nu({\mathbb R}\tilde{A})$. Since ${\operatorname{Log}}|_A$ is at most 2-1 we can view the map ${\operatorname{Log}}\circ\nu:\tilde{A}\to{\mathcal{A}}$ as a branched double covering. Let $F\subset{\mathcal{A}}$ be the branch locus of this covering, i.e. the set of points whose inverse image under ${\operatorname{Log}}|_A$ consists of one point. The involution ${\operatorname{conj}}_{\tilde{A}}$ is the deck transformation of the branched double covering ${\operatorname{Log}}\circ\nu$. The Lemma follows from the fact that ${\operatorname{Log}}$ maps conjugate points to the same point, ${\operatorname{Log}}\circ{\operatorname{conj}}={\operatorname{Log}}$. ${\mathcal{A}}=\tilde{A}/{\operatorname{conj}}_{\tilde{A}}$, while $F={\operatorname{Log}}(\nu({\mathbb R}\tilde{A}))={\partial}{\mathcal{A}}$. The curve $\tilde{A}$ is non-singular and therefore $\tilde{A}/{\operatorname{conj}}_{\tilde{A}}$ is a smooth surface with the boundary ${\mathbb R}\tilde{A}$. Thus ${\partial}{\mathcal{A}}$ consists of the images of components of ${\mathbb R}\tilde{A}$. These components are of two types, closed components, called [*ovals*]{}, and non-compact components. Accordingly, each oval of ${\mathbb R}A$ which does not contain singular points corresponds to a hole in ${\mathcal{A}}$. Consider first the case when $A$ is a non-singular curve, so that $\tilde{A}=A$. Let $l$ be the number of ovals of ${\mathbb R}A$. Then $\chi({\mathcal{A}})=1-l$, where $\chi$ stands for the homology Euler characteristic, i.e. the alternated sum of Betti numbers (we specify that since ${\mathcal{A}}$ is not compact). On the other hand, by additivity of Euler characteristic for compact spaces, $\chi(\bar{A})=2\chi({\mathcal{A}})=2-2l$ (recall that $\bar{A}$ is a compactification of $A$ in a suitable toric surface, see Section \[harnackcurves\]). But $\chi(\bar{A})=2-2g$ and, therefore, $l=g$. To ensure that ${\mathbb R}A$ has the right number of non-compact components we recall that $\bar{A}$ intersect the complexification of $l_k$ in $d_k$ points. Each such intersection corresponds to a “tentacle” of ${\mathcal{A}}$ which goes to infinity (see [@GKZ]). Therefore ${\mathbb R}^2{\smallsetminus}{\mathcal{A}}$ has $\sum\limits_{k=1}^n d_k$ non-compact components and each of them must be bounded by a non-compact component of ${\mathbb R}A$. To finish the proof in the case when $A$ is non-singular we need to show that these $g+\sum\limits_{k=1}^n d_k$ components of ${\mathbb R}A$ are arranged in ${({\mathbb R}^*)^2}$ in the Harnack way. This follows from Lemma 11 of [@Mi]. Compactifying with $l_1\cup\dots \cup l_n$ we obtain that $({\mathbb R}T_\Delta;{\mathbb R}\bar{A},l_1\cup\dots\cup l_n)$ is a Harnack arrangement. Now we consider a general case where $A$ might have singular points. $A$ has no singularities other than real isolated double points. We claim that the singular points of $A$ may only arise as the intersection points of two non-singular branches of $\tilde{A}$. Consider the map $\tilde{A}\to A\to {\mathcal{A}}$. Over ${\mathcal{A}}{\smallsetminus}F$ each of the two branches of $\tilde{A}$ must be non-singular. Indeed, it maps 1-1 to ${\mathcal{A}}{\smallsetminus}F$ and, therefore, the link of each point of this branch is an unknot. By a similar reason branches of $\tilde{A}$ cannot have singular points over $F$. Indeed, the links of such points are unknots since neighborhoods of those points map 2-1 to small half-disks from $\tilde{A}/{\operatorname{conj}}_{\tilde{A}}$. By Lemma 1 of [@Mi] the image of each branch of $\tilde{A}$ under ${\operatorname{Log}}$ has a convex complement. Therefore the images of branches of ${\mathbb R}\tilde{A}$ cannot intersect (that would produce points of ${\mathcal{A}}$ with at least 4 inverse images under ${\operatorname{Log}}|_A$). Thus the only singularities of $A$ are intersection points $p$ of a pair of conjugate non-singular imaginary branches. If these branches are not transverse then they have a real tangent line $\tau$. The points of $\tau$ close to $p$ will be covered at least twice by each of the two branches of $\tilde{A}$ which leads to a contradiction. We conclude that the only singularities of $A$ are $A_1^+$-singularities. Now we may replace each $A_1^+$-point with a small oval that corresponds to its local perturbation and proceed similar to the case of non-singular curves. Implication $3\implies 2$. -------------------------- This implication is contained in the proof of the main theorem in [@Mi]. Indeed, a Harnack curve is in cyclically maximal position (see Theorem 3 of [@Mi]). By Lemmas 5 and 8 of [@Mi] we know that $F={\operatorname{Log}}({\mathbb R}A)={\partial}{\mathcal{A}}$ and by Lemma 9 ${\operatorname{Log}}|_{{\mathbb R}A}$ is an embedding. Therefore the only singularities of ${\operatorname{Log}}|_A$ are folds and ${\operatorname{Log}}|_A$ is at most 2-1. [aaaaaaaaa]{} A.D. Aleksandrov, [*Zur Theorie von konvexen K[œ]{}rpern IV: Die gemischten Diskriminanten und die gemischten Volumina,*]{} [*Matem. Sb. SSSR*]{} [**3**]{} (1938), 227 - 251. V.I. Arnold, A.N. Varchenko, S.M. Gusein-Zade, [*Singularities of differential maps, Vols I and II, Birkhäuser*]{}, Boston, 1985 and 1988. I.M. Gelfand, M.M. Kapranov, A.V. Zelevinsky, [*Discriminants, resultants, and multidimensional determinants.*]{} Birkhäuser, Boston, 1994. A. Harnack, [*Über Vieltheiligkeit der ebenen algebraischen Curven,*]{} Math. Ann. [**10**]{} (1876), 189-199. I. Itenberg, O. Viro, [*Patchworking algebraic curves disproves the Ragsdale conjecture,*]{} Math. Intelligencer [**18**]{} (1996), no. 4, 19 - 28. A.G. Khovanskii, [*Newton polyhedra and toric varieties,*]{} Funkcional. Anal. i Priložen. [**11**]{} (1977), no. 4, 56 - 64. Grigory Mikhalkin, [*Real algebraic curves, moment map and amoebas*]{}, Ann. of Math. 151 (2000), no. 1, 309 - 326. Mikael Passare, Hans Rullg[å]{}rd, [*Amoebas, Monge-Ampère measures, and triangulations of the Newton polytope*]{}. Preprint, Stockholm University, 2000. Jeffrey Rauch, Alan Taylor, [*The Dirichlet problem for the multidimensional Monge-Ampère equation,*]{} Rocky Mountain J. Math. [**7**]{} (1977), 345 - 364. [^1]: The first author is partially supported by the NSF [^2]: In this paper we restrict our attention to functions of two variables. Amoebas are defined for functions of any number of variables. | Mid | [
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Two new vitamin B-12 factors from sewage sludge containing 2-methylsulfinyladenine or 2-methylsulfonyladenine as base component. Two hitherto unknown vitamin B-12 factors were isolated from sewage sludge. They were degraded with cerous hydroxide to cobinamide and the corresponding nucleoside. The nucleosides were further split with dilute hydrochloric acid to the bases and D-ribose. The structure of the two bases was found to be 2-methylsulfinyladenine and 2-methylsulfonyladenine. This was revealed by mass, infrared and nuclear magnetic resonance spectroscopy, and by comparison with the synthetic compounds. On addition of the synthetic bases to fermentations with Propionibacterium acidi-propionici the vitamin B-12 factors containing the corresponding base were formed. They were identical with the 2-methylsulfonyladenylcobamide and 2-methylsulfonyladenylcobamide originally isolated from sewage sludge. | Mid | [
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Understanding how to invest in HMO’s It is no secret that the best returns available for investors in residential lettings come from Houses In Multiple Occupation (HMO’s). This is where a traditional family property is let to a group of unrelated sharers, or is let room-by-room to individual unrelated sharers. This maximises the rent that is achievable since there are several people to split the cost, rather than one family.Why would tenants want to do this? • Bills are typically included in the rent, making this a really convenient way to rent• Rents are much lower than for an entire property making this a highly affordable way to rent• It’s a fantastic way to meet new people! Most tenants renting in HMO’s are in their 20’s and this age group love to socialise. Not only that Leeds is a magnet for employment for young people. Meeting new people is a priority for those moving to a new city. What better way to do that but to move into a house share? Whilst we have seen investor demand increasing for HMO’s in recent years to an extent, many choose to stay away from this area. The reasons we hear for this tends to around these concerns: • Difficulties getting planning permission, particularly in an Article 4 area• Difficulties getting finance• Belief there is too much regulation/a misunderstanding of regulation/no time to learn this complex area• Too much cost to set up the property to be a HMO• Too management intensive• Too much wear and tear on the property• High tenant turnover and or void periods Whilst these are valid concerns, after years of letting and managing HMO’s as well as investing ourselves, Dwell Leeds have been able to overcome all of these areas through experience and their understanding and knowledge of the market. We have successfully eliminated all of these concerns on many projects and we’re fantastically placed to help others to do the same. This means we are able to achieve some of the highest yields out there for investors in Leeds! Because this market remains shrouded in misunderstanding and seeming complexity, many landlords avoid it altogether which makes for a less competitive field for the investors that are “in the know”. The informed investors also understand that the true value in HMO’s comes from outsourcing the “hard work”, time consuming, nitty gritty stuff to a professional agent that really understands this area. This frees up their time and energy so they can focus on the more important things in life. This could be income generating activities such as finding more deals, more time to spend on their career. It also enables them to spend more time on the things they love – family, or hobbies. Our investors leverage our time, systems, knowledge, experience and team. In this way they create fabulous passive incomes for themselves without any hassle. This is the path to wealth creation. What are the returns? This varies but generally they can be around double the return for a HMO than a single let. An average single let property in Leeds is around 5% net return, whereas the average HMO is close to a 10% net return (after all costs), although they can be higher. Does this sound interesting to you? In a series of upcoming blogs, I’ll address each of the typical concerns to show you how you can understand and master HMO investing. The next blog will focus on achieving planning permission, which can be the most challenging hurdle. This can be challenging in Leeds since most of Leeds is within an Article 4 area, however it can be done. If you are not familiar with Article 4, this is a direction imposed by the local authority to restrict the use of HMO’s in a given location. | High | [
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1. Introduction {#sec1} =============== Splenic vein thrombosis (SVT) is known as one of the rare causes of upper gastrointestinal bleeding and is mostly seen in the fifth decade of life and male sex \[[@B1], [@B2]\]. So far, 37 different etiologies have been reported for SVT \[[@B3]\]. The typical manifestations are bleeding from gastric varices characterized by anemia, hematemesis, melena, or hematochezia seen in 15%--50% of patients. Splenomegaly is observed in all patients with SVT whether it be in physical examination or imaging evaluation or during surgery \[[@B3]\]. Sometimes other symptoms of splenomegaly such as thrombocytopenia or pancytopenia and abdominal pain are also manifestations of the disease \[[@B4]\]. It must be noted that since liver cirrhosis is absent in SVT, these patients do not have chronic liver disease \[[@B4]\]. Being asymptomatic, in most cases, makes the diagnosis of SVT difficult. However reports of SVT have increased in recent years which could be due to advancement in imaging techniques \[[@B5]\]. Previously, though, most cases of SVT were distinguished in postmortem autopsy but now with the developments such as celiac angiography and splenoportography most cases are readily detectable. Since abdominal CT is used for patients with acute pancreatitis as well as preoperative patients of chronic pancreatitis, SVT is often an incidental finding in the computerized tomography (CT) scan \[[@B5]\]. The diagnosis test of choice for the assessment of SVT is venous-phase celiac angiography \[[@B5]\]. This condition results in increased localized sinistral portal pressure, which is also known as sinistral portal hypertension. The majority of patients with SVT and the resulting sinistral portal hypertension, in contrast to patients with generalized portal hypertension, are asymptomatic and have normal hepatic function. Gastrointestinal bleeding secondary to esophageal or gastric varices may occur in these patients ([Figure 1](#fig1){ref-type="fig"}). Most patients with SVT have peripheral arteries other than gastric varices which never go bleeding. As a result asymptomatic patients without gastric varices should be monitored and do not need treatment for SVT \[[@B4]\]. In other words SVT alone does not need treatment. In symptomatic patients splenectomy is the treatment of choice done by shunting collateral flow \[[@B4]\]. 2. Case Report {#sec2} ============== Patient was an 8-year-old boy referred to our center with massive upper gastrointestinal bleeding. The patient was found to have splenomegaly. He went through multiple evaluations including endoscopy and underwent band ligation for progressive esophageal varices. The patient had no history of neonatal blood exchange and umbilical venous catheters during infancy. No finding suggestive of portal venous thrombosis was observed in Doppler sonography. All the experiments indicated normal hepatic function. Due to recurrent bleeding and signs of hypersplenism and bicytopenia (thrombocytopenia and anemia), CT scan in venography phase was performed, which presented suspicious findings in splenic vein. Patient\'s CT angiography of the abdomen revealed splenomegaly ([Figure 2](#fig2){ref-type="fig"}), dilation and tortuosity of spleen hilum veins and veins lining the esophagus and stomach ([Figure 3](#fig3){ref-type="fig"}), and dilation of coronary and left renal veins ([Figure 4](#fig4){ref-type="fig"}). Haziness was observed throughout the mesenteric fat of the spleen hilum and splenic vein pathway. However, the size and density of the pancreas were normal. Additionally, lipase and amylase levels were also normal both in initial evaluations and in subsequent follow-ups. Given the portal hypertension symptoms and the history of cytopenia and splenic vein thrombosis, complementary evaluations were made considering PNH. Flow cytometry of peripheral blood was carried out on white blood cells in which CD55 and CD59 were reported as 90% positive. Gallbladder as well as intra- and extrahepatic biliary ducts were seen as normal. Splenorenal shunt was observable through left renal vein and splenogastric shunt was visible because of the tortuosity and dilation of gastric veins and enlargement of coronary vein. Regarding the clinical status of the patient, such as recurrent bleeding and failure to respond to band ligation in the specified time, the patient was scheduled for surgery. He underwent laparotomy under general anesthesia and in sterile conditions. The laparotomy findings were as follows: normal liver in inspection and palpation. There were plenty of omental adhesion bands surrounding the spleen. The spleen was larger than usual. Dilated veins surrounding the spleen and stomach and esophagus were observed. To release adhesions surrounding the spleen, the splenic vessels ligations were cut. Splenectomy was completed. It is worth noting that, due to signs of hypersplenism and the presence of splenic thrombosis, diagnostic assessments were done prior to surgery on MPS including ET and PV. JAK2 mutation was checked and reported as negative. Aspiration and bone marrow biopsy were also performed which reported bone marrow as normocellular and reactive. During the one-year follow-up the patient did not go into relapse and control endoscopies showed improvement of esophageal varices. In the assessments that followed hereditary deficits of pro S, pro C and Antithrombin III were checked for and reported as negative. The normal values are added to [Table 1](#tab1){ref-type="table"}. 3. Discussion {#sec3} ============= Portal hypertension resulting from SVT can lead to massive gastrointestinal bleeding from esophageal or gastric varices or cause hypertensive gastropathy \[[@B1]\]. In 7%--20% of patients SVT is accompanied by acute and chronic pancreatitis, pancreatic pseudocysts, and pancreatic adenocarcinoma \[[@B1], [@B2]\]. Even after recovery, symptoms of pancreatitis have been reported \[[@B1], [@B4]\]. The most common cause of SVT is chronic pancreatitis and perivenous inflammation \[[@B4]\]. Although SVT has been reported in more than 45% of patients with chronic pancreatitis, most of SVT patients are asymptomatic \[[@B3]\]. Pancreatitis leading to SVT may be mild and the patients show no clinical sign indicating chronic pancreatitis \[[@B3]\]. Unlike patients with portal vein hypertension, most patients with SVT are asymptomatic and have normal hepatic function \[[@B4]\]. SVT can cause localized hypertension of splenic veins and create collaterals from spleen to the fundus. From that point, blood returns to the main portal system via coronary vein. In such a case, gastric varices are not often associated with esophageal varices except for collaterals at the site of gastroesophageal junction, where bleeding is common. In other cases, despite the formation of large and multiple collaterals, spontaneous bleeding seldom occurs. Patients with the following characteristics are suspected of having SVT \[[@B4]\]: patients with history of pancreatitis or GI bleeding, patients with splenomegaly without portal vein hypertension, cirrhosis, or hematologic disease, and finally patients with gastric varices alone. There are other reasons for gastric bleeding in patients with chronic pancreatitis which include the following: arterial pseudoaneurysm, pancreatic pseudocysts, hemosuccus pancreaticus, peptic ulcer disease, gastritis, and Mallory-Weiss tears \[[@B7]\]. Therefore, an overall assessment in patients with SVT and gastrointestinal bleeding is necessary as less than half the bleeding is related to gastric varices. SVT in acute or chronic pancreatitis results from factorial perivenous inflammation and includes intrinsic endothelial damage caused by inflammation and extrinsic damage secondary to venous pressure resulting from fibrosis, adjacent pseudocysts, or edema \[[@B3]\]. In any patient with signs of splenic vein thrombosis and the resulting hypersplenism, the underlying cause for hypercoagulation state should be investigated. Hypercoagulable states are inherited or acquired conditions. They are associated with a predisposition to vein thrombosis. These include a wide range of thrombolytic disorders throughout the body such as brain vein thrombosis, extremity deep venous thrombosis, arterial thrombosis (such as stroke, myocardial infarction), and intra-abdominal venous thrombosis. The most prevalent clinical feature resulting from hypercoagulable states is venous thromboembolic disease. Some other resulting disorders include myeloproliferative and hyperhomocysteinemia syndromes and antiphospholipid antibodies (APAs). As mentioned earlier our patient turned negative for MPS but in the subsequent tests blood homocysteine level was checked to be normal. APS panel was checked to show no specific underlying disorder (values are cited in [Table 1](#tab1){ref-type="table"}) \[[@B8]\]. Obstruction of the splenic vein could result from enlarged retroperitoneal lymph nodes and pancreatic or perisplenic nodes \[[@B3]\]. These lymph nodes surround splenic veins and if they get enlarged due to inflammation or malignancy, put pressure on veins and cause obstruction and thrombosis \[[@B7]\]. Despite earlier reports pointing to pancreatic carcinoma as the most common cause of SVT \[[@B7], [@B9]\] most recent studies conclude that acute or chronic pancreatitis particularly in pancreatic tail is the probable cause of SVT in most patients \[[@B1], [@B9]\]. Pancreatitis is the initiating cause of thrombosis in 60% of patients; however, diagnosis of SVT in these patients does not always occur during an acute attack \[[@B3], [@B9]\]. Other causes for SVT include the following: adenopathy of metastatic carcinoma and lymphoma and iatrogenic reasons after operations such as partial gastrectomy and distal splenorenal shunt \[[@B1], [@B2]\]. Splenectomy is the treatment of choice for SVT \[[@B5]\]. In patients with gastric varices bleeding resulting from SVT, splenectomy must be done as an emergency because gastric varices have a relatively higher potential for massive bleeding than esophageal varices. And also no other treatment is available to put the bleeding under control \[[@B7], [@B10]\]. The role of prophylactic splenectomy in asymptomatic patients is still controversial. Previous studies showed high rates of variceal hemorrhage in patients with SVT; therefore many authors recommended splenectomy in this group of patients. But recent studies indicate that gastric varices bleeding only occurs in 40% of patients and thus prophylactic splenectomy is not recommended \[[@B7]\]. In this case no underlying disorders such as pancreatic associated etiologies (e.g., traumas, gastric operations, umbilical vein catheterizations, malignancies, retroperitoneal disease, splenic artery aneurysms, myeloproliferative disease, protein S deficiency, protein C deficiency, antithrombin III deficiency, and factor V Leiden mutation) were present and no evidence of antiphospholipid syndrome was seen. This convinced us that this case was interesting enough to be reported as an idiopathic isolated splenic vein thrombosis case. Conflict of Interests ===================== The authors declare that there is no conflict of interests regarding the publication of this paper. ![The effects of splenic vein thrombosis on normal venous anatomy. Note the gastric varices, dilatation of short gastric, and gastroepiploic (GEV) and coronary (CV) veins. The portal vein (PV), superior mesenteric vein (SMV), and inferior mesenteric vein (IMV) are patent. RGV: right gastric vein; SV: splenic vein \[[@B6]\].](CRIPE2015-480507.001){#fig1} {#fig2} {#fig3} {#fig4} ###### Laboratory evaluation. ------------------------ --------------------------- Beta 2 GP1 level IgG 4.3 AU/mL (normal: \<5) IgM 3.2 AU/mL (normal: \<8) IgA 2.4 AU/mL (normal: \<8) Anticardiolipin Ab IgM 9.63 MPL/mL Lupus anticoagulant Ab Absent Protein C 85.6 (normal: 70%--130%) Protein S 120.2 (normal: 77%--143%) Antithrombin III 97% (normal: \>75%) Factor V Leiden Absent ------------------------ --------------------------- [^1]: Academic Editor: Denis A. Cozzi | Mid | [
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Pierre Janet and the breakdown of adaptation in psychological trauma. In this reappraisal of the work of Pierre Janet at the centenary of the publication of L'automatisme psychologique, the authors review his investigations into the mental processes that transform traumatic experiences into psychopathology. Janet was the first to systematically study dissociation as the crucial psychological process with which the organism reacts to overwhelming experiences and show that traumatic memories may be expressed as sensory perceptions, affect states, and behavioral reenactments. Janet provided a broad framework that unifies into a larger perspective the various approaches to psychological functioning which have developed along independent lines in this century. Today his integrated approach may help clarify the interrelationships among such diverse topics as memory processes, state-dependent learning, dissociative reactions, and posttraumatic psychopathology. | High | [
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On today’s episode of Electric LibertyLand host Brian McWilliams welcomes in Lions co-founder and host of Felony Friday John “Odie” Odermatt to discuss the topics of the day. Brian takes on some topics flying solo, including Sen. Jeff Sessions hearings for the position of Attorney General, Dylan Roof’s death sentence for a hate crime, and the alleged connections to Russia included in a controversial new report. Brian and Odie boogie break down Austin Petersen’s flirtations with running as a Republican, Meryl Streep’s tone-deaf smugfest at the Golden Globes, Donald Trump Jr.’s push to make silencers more accessible and hear a word from our show sponsor “Trump Thwumps.” Odie and Brian wrap it up with a look at a Obamacare love affair between Rand Paul and the Donald, then turn to climate science expert and voice of skeptical reason Judith Curry’s resignation from Georgia Tech. Let’s hit the dance floor. Download this episode (right click and save) Discussed in this Episode: Discuss this and much more in our private Facebook Group: The Lions of Liberty Forum! Never miss an episode of the Lions of Liberty Podcast and subscribe for free via iTunes (don’t forget to leave us a rating and review )- or the Stitcher Radio App. Check out our full catalog of interviews in the podcast archive. The Lions of Liberty are on Twitter, Facebook & check out our YouTube Channel! Receive access to ALL of our EXCLUSIVE bonus audio content – including “Conspiracy Corner”, “Degenerate Gamblers” and the “League of Liberty Podcast” by joining the Lions of Liberty Pride and supporting us on Patreon! | Mid | [
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Assessing the influence of SNR and pre-processing filter bandwidth on the extraction of different muscle co-activation indexes from surface EMG data. Muscle co-activation is the mechanism that regulates simultaneous activity of agonist and antagonist muscles crossing the same joint. During functional movements, robust measurement techniques are required for an accurate determination of muscle co-activation, since various environmental and processing factors in the surface electromyography (sEMG) measurement process might influence the estimation of linear envelope profiles, and therefore the outcome of co-activation evaluated from the signal envelope. The aim of this study is to verify the performance of the co-activation indexes introduced in six different techniques used to assess muscle co-activation. A sensitivity analysis with respect to both noise and pre-processing choices for envelope estimation has been done by using a data-set of simulated sEMG signals. The results show how the indexes are affected by both the level of noise and pre-processing choices. The Vector Coding Technique and the Time-varying Multi-muscle approach perform better than the others in terms of both sensitivity to varying levels of co-activation and robustness to noise. | High | [
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Hop til / Skip to: New forage plant prepares farmers for climate changes Plant patent Researchers, including plant researchers from the University of Copenhagen, have developed a new type of the corn-like crop sorghum, which may become very significant for food supplies in drought-prone areas. Unlike the conventional drought-resistant sorghum plant, which is an important crop in e.g. Africa, China and the USA, this new type does not form toxic cyanide when exposed to long-term drought. Consequently, farmers in drought areas will no longer need to discard their sorghum crops in future. Photo: Peter Stuart Sorghum, or durra, is an important forage crop in many countries, for example the USA, Africa, China and Australia. The plant is grown instead of corn because it produces more biomass and better withstands long periods of drought. However, when exposed to drought, the sorghum plant produces large amounts of dhurrin, which forms toxic cyanide, i.e. Prussic acid. Forced to discard crops Farmers thus face a big dilemma. During a period of drought when they most need food for their animals, they are often forced to discard their sorghum because they do not know how poisonous it is and how much the animals can eat without suffering from cyanide poisoning. In Australia alone, farmers lose hundreds of millions of dollars each year as a result: Photo: Peter Stuart "The fact that the sorghum plant produces large amounts of the natural cyanogenic glycoside dhurrin when exposed to drought is a serious problem for farmers in many parts of the world. Dhurrin breaks down to form toxic cyanide or Prussic acid when an animal eats the plant. So when there is a drought and most need for forage, the farmer can no longer use the crop and it goes to waste," says Professor of Plant Biochemistry at the University of Copenhagen, Birger Lindberg Møller . New, toxic-free sorghum strain is a breakthrough Recently, Birger Lindberg Møller and his research group have, in collaboration with, for example, Monash University in Australia, developed a sorghum plant which is unable to produce Prussic acid. Instead of using genetic engineering, the researchers used plant breeding and advanced biochemical and molecular biological screening methods: "This is a breakthrough which, globally, can be very important for agriculture, especially in warmer climes where climate change is expected to cause longer and more frequent periods of drought in future. Especially inAfrica, where farmers cannot afford to buy new forage in periods of drought, it is a huge step forwards that they will now be able to feed their animals with sorghum they can grow themselves," says Birger Lindberg Møller. The University of Copenhagen and Monash University have submitted a patent application. Copenhagen Plant Science Center gathers plant research Professor Birger Lindberg Møller is an internationally leading researcher in explaining the way in which plants produce bioactive natural substances. This research area will be a key part of the research profile for the future Copenhagen Plant Science Center . The centre will bring together the University of Copenhagen’s research and education within plants and plant-based foods and provide even better possibilities for working with the business sector. On Wednesday 28 March, Maive Rute, Director for Food, Agriculture and Biotechnology in the EU Commission, visited some of the research environments which in future will make up theCopenhagen Plant Science Center. The purpose of the visit was to examine the possibilities for major new EU initiatives and investments in the plant and energy area: "The visit is important because in future it will increasingly enable Danish research results to be translated in collaboration with both small and larger businesses into specific products and developing strategies which can counter some of the challenges posed by climate change in terms of reduced yields and the spread of new plant diseases. There is a serious need for knowledge-based solutions within bioenergy, foods, medicine and other bio-based raw materials which can benefit research and business," says Professor Poul Erik Jensen , who, with Professor Birger Lindberg Møller, is an acting head of the centre. New non-toxic sorghum Researchers from the Faculty of Science at The University of Copenhagen, Monash University in Australia and the Australian plant breeding company Pacific Seeds have developed a new type of sorghum, or durra as it is also known, which does not produce the toxin dhurrin. Using a population of tens of thousands of sorghum plants in an open field trial, the researchers analysed their way to finding individual sorghum plants which carried a mutation of just one of the genes involved in producing dhurrin. Some of these plants are completely unable to form dhurrin, while others only produce it a couple of weeks after the sorghum seed has germinated. Dhurrin is a bioactive natural substance belonging to the group of cyanogenic glycosides. The researchers used effective biochemical and molecular screening methods developed at The University of Copenhagen. In the plant, which is unable to form dhurrin, a single amino acid has been changed out of a total of 558 amino acids which make up the enzyme. This single change means that the enzyme is inactive. This plant is now used for the subsequent breeding work. Non-toxic strains of sorghum are expected to be on the market within a few years. | Mid | [
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Donald Trump riled up his supporters in Florida on Friday, saying Iranian ships harassing the US Navy would be 'shot out of the water' under his presidency. 'With Iran, when they circle our beautiful destroyers with their little boats and they make gestures at our people that they shouldn't be allowed to make, they will be shot out of the water,' Trump said. Last weekend, an Iranian boat came within 100 yards of a US coastal patrol ship in the Persian Gulf, forcing the USS Firebolt to maneuver out of the way in the fourth confrontation in the past month. Donald Trump riled up his supporters in Pensacola, Florida, on Friday, saying Iranian ships harassing the US Navy would be 'shot out of the water' under his presidency Republican presidential candidate Donald Trump gives a thumbs up as he speaks during a rally in Pensacola His incendiary comment, which would most likely launch the country in a war if it was carried out, came after recent confrontations between the US and Iran on international waters While Trump has tried to soften his tone and stick to teleprompters in the three weeks after his campaign shake-up, Friday's rally showed signs he was reverting to his controversial ways. His incendiary comment, which would most likely catapult the country in a war if it was carried out, came after a series of recent confrontations between the US and Iran on international waters. And yet Trump accused Hillary Clinton of being 'trigger-happy' on Friday, calling her an 'unstable person' whose policies 'produced only death, destruction and not diplomacy'. This week, the Republican presidential nominee laid out a multi-billion dollar plan to bolster the military, which would become 'so strong that nobody's going to mess with us'. And thousands of supporters applauded his taunts in Florida on Friday, and later cheered 'USA! USA!' in response. Trump has based his foreign policy beliefs on keeping the United States out of what he called 'endless wars' in the Middle East. The business tycoon, who has been criticized for his frequent praise of Russian President Vladimir Putin, also mentioned a recent incident in which a Russian fighter jet came within 10 feet of a US Navy surveillance plane over the Black Sea. 'Putin laughs, believe me, he laughs at our leaders. Yesterday he had a plane 10 feet away, taunting us, toying with us, just like Iran,' he said. The USS Firebolt (file photo from 2011) was forced to change course after an Iranian Navy patrol boat came within 100 yards of it last Sunday despite repeated warnings The incident came after the USS Nitze fired flares at Iranian patrol boats after the approached at speed and in an 'unsafe and unprofessional' manner, officials said The confrontations are taking place in a narrow band of international water that runs between Iran on one side and the United Arab Emirates on the other He also said Hillary could kill someone and get away with it because she avoided prosecution in regards to her use of a private email server. 'Because she's being so protected, she could walk into this arena right now and shoot someone with 20,000 people watching, right smack in the middle of the heart, and she wouldn't be prosecuted,' Trump said. His comment was reminiscent of his own popularity claims in January, when he told supporters in Iowa: 'I could stand in the middle of 5th Avenue and shoot somebody and I wouldn't lose voters.' | Low | [
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=ZTree v3.x (JQuery Tree插件) 更新日志= <font color="red">为了更好的优化及扩展zTree, 因此决定升级为v3.x，并且对之前的v2.x不兼容，会有很多结构上的修改，对此深感无奈与抱歉，请大家谅解。</font> <font color="red"> 具体修改内容可参考： * [http://www.ztree.me/v3/api.php zTree v3.0 API 文档] * [http://www.ztree.me/v3/demo.php#_101 zTree v3.0 Demo 演示] * [http://www.ztree.me/v3/faq.php#_101 zTree v3.0 常见问题] </font> <font color=#041594> *2013.03.11* v3.5.12 * 【修改】由于 jquery 1.9 中移除 event.srcElement 导致的 js 报错的bug。 * 【修改】在异步加载模式下，使用 moveNode 方法，且 moveType != "inner" 时，也会导致 targetNode 自动加载子节点的 bug * 【修改】对已经显示的节点(nochecked=true)使用 showNodes 或 showNode 方法后，导致勾选框出现的bug。 * 【修改】对已经隐藏的节点(nochecked=false)使用 hideNodes 或 hideNode 方法后，导致勾选框消失的bug。 * 【修改】getNodesByParamFuzzy 支持 大小写模糊。 * 【修改】className 结构，提取 _consts.className.BUTTON / LEVEL / ICO_LOADING / SWITCH，便于快速修改 css 冲突。 例如：与 WordPress 产生冲突后，直接修改 core 中的 "button" 和 "level" 即可。 Issue: https://github.com/zTree/zTree_v3/issues/2 *2013.01.28* v3.5.02 * 【增加】setting.check.chkDisabledInherit 属性，用于设置 chkDisabled 在初始化时子节点是否可以继承父节点的 chkDisabled 属性 * 【删除】内部 noSel 方法，使用 selectstart事件 和 "-moz-user-select"样式 处理禁止 节点文字被选择的功能 * 【修改】不兼容 jQuery 1.9 的bug * 【修改】onDrop 的触发规则，保证异步加载模式下，可以在延迟加载结束后触发，避免 onDrop 中被拖拽的节点是已经更新后的数据。 * 【修改】setChkDisabled 方法，增加 inheritParent, inheritChildren 参数设置是否让父子节点继承 disabled * 【修改】异步加载时 拼接参数的方法，由 string 修改为 json 对象 * 【修正】1-2-3 3级节点时，如果 2级节点 全部设置为 nocheck 或 chkDisabled后，勾选3级节点时，1级节点的半勾选状态错误的 bug * 【修改】Demo: checkbox_nocheck.html & checkbox_chkDisabled.html; * 【修改】Demo: edit_super.html，增加 showRenameBtn & showRemoveBtn 的演示 * 【修改】Demo: asyncForAll, 将 post 修改为 get；为了避免由于 IE10 的 bug 造成的客户端 以及 服务端崩溃 IE10 ajax Post 无法提交参数的bug (http://bugs.jquery.com/ticket/12790) *2012.12.21* v3.5.01 * 【优化】clone 方法 * 【修正】对于初始化无 children 属性的父节点进行 reAsyncChildNodes 操作时出错的 bug * 【修正】beforeRename 回调中使用 cancelEditName 方法后，再 return false 导致无法重新进行编辑的 bug * 【修正】exedit 扩展包让 setting.data.key.url 失效的 bug * 【修正】setting.check.autoCheckTrigger 设置为 true 时，onCheck 回调缺少 event 参数的 bug * 【修正】singlepath.html Demo 中的 bug *2012.11.20* v3.5 * 【优化】原先的 clone 方法 （特别感谢：愚人码头） * 【修改】隐藏父节点后，使用 expandAll 方法导致 父节点展开的 bug * 【修改】使用 jQuery v1.7 以上时，设置 zTree 容器 ul 隐藏（visibility: hidden;）后， 调用 selectNode 导致 IE 浏览器报错 Can't move focus 的 bug * 【修改】正在异步加载时，执行 destory 或 init 方法后，异步加载的节点影响新树的 bug * 【修改】方法 reAsyncChildNodes 在 refresh 的时候未清空内部 cache 导致内存泄露 的 bug * 【修改】批量节点拖拽到其他父节点内（inner）时，导致顺序反转 的 bug * 【修改】对于 使用 html格式的 节点无法触发 双击事件 的 bug * 【修改】onCheck 回调中的 event ，保证与触发事件中的 event 一致 * 【修改】异步加载时，在 onNodeCreated 中执行 selectNode 后，导致节点折叠的 bug * 【修改】API 中 dataFilter 的参数名称 childNodes -> responseData * 【修改】API 中 iconSkin 的 举例内容 * 【修改】API 中 chkDisabled 的说明 * 【修改】Demo 中 index.html 内的 loadReady 重复绑定问题 *2012.09.03* v3.4 * 【增加】 Demo —— OutLook 样式的左侧菜单 * 【增加】清空 zTree 的方法 $.fn.zTree.destory(treeId) & zTree.destory() * 【修改】core核心文件内 _eventProxy 方法中获取 tId 的方法，提高 DOM 的灵活性 * 【修改】初始化时 多层父节点的 checkbox 半选状态计算错误的 bug * 【修改】同时选中父、子节点后，利用 getSelectedNodes 获取选中节点并利用 removeNode 删除时报错的 bug * 【修改】treeNode.chkDisabled / nocheck 属性，支持字符串格式的 "false"/"true" * 【修改】异步加载模式下无法利用 server 返回 xml 并且 在 dataFilter 中继续处理的 bug * 【修改】title 只允许设置为 string 类型值的问题。 修正后允许设置为 number 类型的值 * 【修改】zId 计数规则 & Cache 保存，减少 IE9 的 bug 造成的内存泄漏 * 【修改】API 页面搜索功能导致 IE 崩溃的 bug *2012.07.16* v3.3 * 【增加】扩展库 exhide -- 节点隐藏功能 * 【修改】getNodesByFilter 方法，添加 invokeParam 自定义参数 * 【修改】拖拽中测试代码未删除，导致出现黄颜色的 iframe 遮罩层的 bug * 【修改】延迟加载方法 对于使用 expandAll 进行全部展开时，导致 onNodeCreated 回调 和 addDiyDom 方法触发过早的 bug * 【修改】使用 moveNode 移动尚未生成 DOM 的节点时，视图会出现异常的 bug * 【修改】删除节点后，相关节点的 isFirstNode 属性未重置的 bug * 【修改】getPreNode(),getNextNode() 方法在对于特殊情况时计算错误的 bug * 【修改】设置 title 之后，如果重新将 title 内容设置为空后，会导致无法更新 title 的 bug * 【修改】针对 setting.check.chkStyle=="radio" && setting.check.radioType=="all" 的情况时，getTreeCheckedNodes方法优化，找到一个结果就 break * 【修改】zTreeObj.getCheckedNodes(false) 在 radioType = "all" 时计算错误的 bug * 【修改】完善 API 中 beforeDrop / onDrop 的关于 treeId 的说明 *2012.05.13* v3.2 * 【增加】setting.data.key.url 允许修改 treeNode.url 属性 * 【增加】getNodesByFilter(filter, isSingle) 方法 * 【增加】"与其他 DOM 拖拽互动" 的 Demo (http://www.ztree.me/v3/demo.php#_511) * 【增加】"异步加载模式下全部展开" 的 Demo (http://www.ztree.me/v3/demo.php#_512) * 【修改】代码结构，将 addNodes、removeNode、removeChildNodes 方法 和 beforeRemove、onRemove 回调 转移到 core 内 * 【修改】IE7的环境下无子节点的父节点反复展开出现多余空行的 bug * 【修改】异步加载时，如果出现网络异常等，会导致 图标显示错误的 bug * 【修改】dataFilter中 return null 导致异常 的 bug * 【修改】removeChildNodes 方法清空子节点后，无法正常添加节点的 bug * 【修改】moveNode 后节点中的自定义元素的事件丢失的 bug * 【修改】moveNode 方法中设置 isSilent = true 时，如果移动到已展开的 父节点后，出现异常的 bug * 【修改】onClick/onDrag/onDrop 回调中 event 不是原始 event 的 bug * 【修改】onDrop 回调中 当拖拽无效时，无法获得 treeNodes 的 bug * 【修改】onDrop 无法判断拖拽是 移动还是复制的问题 * 【修改】未开启异步加载模式时，拖拽节点到子节点为空的父节点内时 出现异常 的 bug * 【修改】拖拽过程中，反复在 父节点图标上划动时，会出现停顿的 bug (需要css 结构—— button -> span.button) * 【修改】拖拽操作时箭头 与 targetNode 背景之间的细节现实问题，便于用户拖拽时更容易区分 prev、next 和 inner 操作 * 【修改】拖拽操作时IE6/7 下 在 节点<a> 右侧 10px 内会导致 targetNode = root 的 bug * 【修改】编辑模式下 默认的编辑按钮、删除按钮点击后，如果相应的 before 回调 return false 时会触发 onClick 回调的 bug *2012.02.14* v3.1 * 【增加】ajax 的参数 setting.async.contentType ，让提交参数适用于 json 数据提交 （主要适用于 .Net 的开发）。 * 【增加】setting.edit.editNameSelectAll, 用于设定编辑节点名称时初次显示 input 后 text 内容为全选 * 【修改】异步加载 规则，不再仅仅依靠父节点的子节点数来判定，增加内部属性 zAsync，保证默认状态下父节点及时无子节点也只能异步加载一次，除非使用 reAsyncChildNodes 方法强行控制异步加载。 * 【修改】放大浏览器后导致 界面出现多余连接线的bug （需要更新：icon 图标和 css ） * 【修改】在编辑状态，如果节点名超过编辑框宽度，左右键在框内不起作用的bug（IE 6 7 8 出现） CSS 中 filter:alpha(opacity=80) 造成的，应该是 ie 的 bug，需要更新 css 文件 * 【修改】title 设置后，如果属性不存在，则默认为 title 为空，便于数据容错和用户灵活使用 * 【修改】editName 方法如果针对尚未展开的 父节点，会导致该父节点自动展开的 bug * 【修改】title 中存在标签时导致 title 显示异常的bug（例如：蓝色字22%"'`<input/>`） *2012.01.10* v3.0 * 【增加】setting.check.autoCheckTrigger 默认值 false，可以设置联动选中时是否触发事件回调函数 * 【增加】setting.callback.beforeEditName 回调函数，以保证用户可以捕获点击编辑按钮的事件 * 【增加】treeNode.chkDisabled 属性，显示 checkbox 但是用户无法修改 checkbox 状态，并且该 checkbox 会影响父节点的 checkbox 的半选状态 * 【增加】setting.check.nocheckInherit 属性，用户设置子节点继承 nocheck 属性，用于批量初始化节点，不适用于已经显示的节点 * 【增加】setting.edit.drag.autoExpandTrigger 默认值 false，可以设置自动展开、折叠操作时是否触发事件回调函数 * 【增加】setting.view.nameIsHTML 默认值 false，允许用户对 name 设置 DOM 对象 * 【增加】treeNode.click 属性的说明文档 * 【增加】treeObj.setChkDisabled 方法用于设置 checkbox / radio disabled 状态 * 【增加】treeNode.halfCheck 属性，用于强制设定节点的半选状态 * 【修改】异步加载 & 编辑功能 共存时，拖拽节点 或 增加节点 导致 ie 上报错的 bug （apply 方法引起） * 【修改】zTreeStyle 样式冲突 * 【修改】setting.data.key.title 默认值设置为 ""，初始化时自动赋值为 setting.data.key.name 这样可避免希望 title 与 name 一致的用户反复设置参数 * 【修改】点击叶子节点的连接线会触发 expand 事件的 bug * 【修改】IE 下 点击叶子节点连线会出现虚线框的 bug * 【修改】updateNode 导致 checkbox 半选状态错误的 bug * 【修改】checkNode 方法实现 toggle 操作, 取消 expandAll 方法的 toggle 操作 * 【修改】zTree 内鼠标移动会抢页面上 input 内的焦点的 bug * 【修改】beforeRename / onRename 的触发方式——即使名称内容未改变也会触发，便于用户配合 beforeEditName 捕获编辑状态的结束，赋予用户更多调整规则的权利 * 【修改】与 easyUI 共存时无法拖拽的bug * 【修改】beforeRename 在 Firefox 下如果利用 alert，会触发两次的 bug * 【修改】checkNode/expandNode/removeNode 方法，默认不触发回调函数，恢复 v2.6 的默认状态，同时增加 callbackFlag 参数，设置为 true 时，可以触发回调函数 * 【修改】IE9下“根据参数查找节点”的Demo 报错：行14 重新声明常量属性(Demo 自身的问题，定义了history变量) * 【修改】初始化 zTree 时 onNodeCreated 事件回调函数中无法 用 getZTreeObj 获取 zTree 对象的 bug * 【修改】setting.edit.drag.prev / next / inner 参数，增加被拖拽的节点集合 * 【修改】异步加载模式下，otherParam 使用Array数组会出错的 bug。例如： ["id", "1", "name", "test"] * 【修改】FireFox 下多棵树拖拽异常的 bug * 【修改】exedit 中调用 excheck库的方法时没有进行容错处理，导致如果只加入 exedit 而没有 excheck的时候，会出现 js 错误 * 【修改】显示 checkbox 的 zTree 在编辑模式下，移动节点不会更新父节点半选状态的 bug * 【修改】treeNode.childs --> children; treeObject.removeChilds --> removeChildNodes; setting.data.key.childs --> children（英文不好惹的祸！抱歉了！） * 【修改】onRemove 回调中得到的 treeNode 还可以查找 preNode、nextNode 的bug。 修正后，getPreNode 和 getNextNode 都返回 null； 为了便于查找父节点，getParentNode 仍保留 * 【修改】简单数据模式下，如果 id 与 pId 的值相同会导致该节点无法正常加载的 bug * 【修改】移动或删除中间节点会导致最后一个节点连接线图标变小的 bug *2011.09.05* v3.0 beta * 【修改】zTree 的 js 代码架构全面修改，并且拆分 * 【修改】zTree 的 css 样式全面修改，对浏览器可以更好地兼容，同时解决了以前1个像素差的问题 * 【优化】采用延迟加载技术，一次性加载大数据量的节点性能飞速提升 * 【增加】支持多节点同时选中、拖拽 * 【增加】checkNode、checkAllNodes 等多种方法 * 【增加】IE6 自动取消动画展开、折叠的功能 * 【修正】异步加载 & 编辑模式 能够更完美的共存 * 【修正】setting 配置更加合理，并且增加了若干项配置参数 * 【修正】treeNode 节点数据的属性更加合理，并且增加了一些方法 * 【修正】拖拽操作更加灵活方便，更容易制定自己的规则 * 【修正】其他若干修改，详细对比请参考 url：[http://www.ztree.me/v3/faq.php#_101 zTree v3.0 常见问题] | Low | [
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[Multiple skin abscesses caused by Nocardia carnea]. Nocardia carnea was isolated from the subdermal abscesses on the leg and supraclavicular region of a kidney transplanted female patient. | Mid | [
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package suites import ( "context" "fmt" "log" "testing" "time" "github.com/stretchr/testify/suite" ) type BypassPolicyScenario struct { *SeleniumSuite } func NewBypassPolicyScenario() *BypassPolicyScenario { return &BypassPolicyScenario{ SeleniumSuite: new(SeleniumSuite), } } func (s *BypassPolicyScenario) SetupSuite() { wds, err := StartWebDriver() if err != nil { log.Fatal(err) } s.WebDriverSession = wds } func (s *BypassPolicyScenario) TearDownSuite() { err := s.WebDriverSession.Stop() if err != nil { log.Fatal(err) } } func (s *BypassPolicyScenario) SetupTest() { ctx, cancel := context.WithTimeout(context.Background(), 10*time.Second) defer cancel() s.doLogout(ctx, s.T()) s.doVisit(s.T(), HomeBaseURL) s.verifyIsHome(ctx, s.T()) } func (s *BypassPolicyScenario) TestShouldAccessPublicResource() { ctx, cancel := context.WithTimeout(context.Background(), 10*time.Second) defer cancel() s.doVisit(s.T(), AdminBaseURL) s.verifyIsFirstFactorPage(ctx, s.T()) s.doVisit(s.T(), fmt.Sprintf("%s/secret.html", PublicBaseURL)) s.verifySecretAuthorized(ctx, s.T()) } func TestBypassPolicyScenario(t *testing.T) { suite.Run(t, NewBypassPolicyScenario()) } | Mid | [
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Q: Display image on drop down selection change newitem form I'm building a list where I want to show an image of the selected item as it's selected in the drop down in the new item form, I have very little javascript knowledge. I'm using the following script <img id="my_image" src="/mysites/site/AL-03T.PNG" alt="" style="width: 48px; height: 48px;"/><script src="http://code.jquery.com/jquery-1.7.2.min.js" type="text/javascript"></script><script type="text/javascript"> $(document).ready(function(){ $("select[title='Product']").change(function() { document.getElementById("my_image").attr('src',"/mysites/site/" + (select[title='Product']).val() + '.PNG'"); }); }); </script> <img id="my_image" alt=""/> based on this answer Load image depending of selected value of dropdown list - SharePoint Online can someone help? A: There are a few things wrong here First ID's need to be unique in your HTML Second, you are mixing javascript with jQuery and you can do that but there are more simple ways to accomplish what you want. Take a look at this fiddle and see if you get what you need from it. You do still need to load jquery on the page, and also you can wrap the jQuery in a $(document).ready(function(){ .... ALL YOUR CODE HERE. }) If you need some further explination let me know. Hope this helps https://jsfiddle.net/kcode28/mtua4L7c/21/ | Mid | [
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fix for 'identifier "unlink" is undefined' and other similar errors author: Kenneth Hoste (HPC-UGent) --- clipper/sparsehash-2.0.2/src/sparsetable_unittest.cc.orig 2017-02-27 19:11:30.059750601 +0100 +++ clipper/sparsehash-2.0.2/src/sparsetable_unittest.cc 2017-02-27 19:13:28.438628098 +0100 @@ -32,7 +32,7 @@ // Since sparsetable is templatized, it's important that we test every // function in every class in this file -- not just to see if it // works, but even if it compiles. - +#include <unistd.h> #include <sparsehash/internal/sparseconfig.h> #include <config.h> #include <stdio.h> --- clipper/sparsehash-2.0.2/src/hashtable_test.cc.orig 2017-02-27 19:49:55.087723317 +0100 +++ clipper/sparsehash-2.0.2/src/hashtable_test.cc 2017-02-27 19:50:14.027542195 +0100 @@ -43,7 +43,7 @@ // Note that since all these classes are templatized, it's important // to call every public method on the class: not just to make sure // they work, but to make sure they even compile. - +#include <stdint.h> #include <sparsehash/internal/sparseconfig.h> #include <config.h> #include <math.h> --- clipper/sparsehash-2.0.2/src/time_hash_map.cc.orig 2017-02-27 20:00:27.821672176 +0100 +++ clipper/sparsehash-2.0.2/src/time_hash_map.cc 2017-02-27 20:00:57.411387012 +0100 @@ -54,6 +54,7 @@ // // See PERFORMANCE for the output of one example run. +#include <inttypes.h> #include <sparsehash/internal/sparseconfig.h> #include <config.h> #ifdef HAVE_INTTYPES_H | Low | [
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It is ironic that Raja Mahendra Pratap's Jat connection is being used for vote bank politics. He could not have cared less for his caste. He was aware of the hold caste had on people's lives, and...... | Low | [
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Publikationen Konferenzbeitrag (1) Automotive companies tend to apply modular approaches in their product development processes in order to save costs and meet increasingly diversified customer demands. In largely decentralized environments with cross-branded development projects over multiple departments in different sites this modular approach leads to very complex and large data structures. Maintaining consistency and transparency, as well as coordinating information flows in such an environment is a major task which is often accomplished manually. Based on a real world case study, this paper analyzes a key development process: the connection of geometric geometries and logistical data parts. During this time consuming process information carriers geometries and parts with independent lifecycles that are maintained by different stakeholders designer and purchaser of different departments and in this scenario even within multiple brands are linked as these carriers themselves are mutually dependent. This paper then proceeds to model five agent-based architecture variants to support this process. In addition, an algorithm to map geometric and logistical data which aims to relieve the actors involved regarding the organizational overhead is outlined.The paper concludes with a comparison of the different agent architecture variants and emphasizes the most promising variants to partly automate the connection of geometric and logistical data. | High | [
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Ankara is content with illegally shelling Syria from across the border, and sending mercenaries to do the real dirty work For the last few days, reports have been streaming in about Turkey allowing "moderate rebels" to cross its border into Syria in an attempt to stop the advances of the SAA and Kurdish forces. Apparently unwilling to risk direct military intervention without full US support, Ankara has chosen a different strategy: Lob shells across the border, and let mercenaries to do the on-the-ground terrorizing. The latest from the Guardian: The sultan sends in mercenaries At least 500 rebels on Wednesday crossed the Turkish border, a monitor said, and headed for the Syrian town of Azaz in northern Aleppo province where opposition forces have suffered setbacks at the hands of Kurdish fighters. We should point out that the "monitor" cited by the Guardian is none other than the Syrian Observatory for Human Rights, the London-based rumor mill that is most likely a front for western intelligence agencies. But what does this tell us? Our guess is that Turkey might actually be acting unilaterally -- and the west is running out of patience. Let's not forget that the Kurds being targeted by Ankara continue to receive diplomatic and military backing from the US. But how accurate is this report? We would bet it's right on the money -- maybe even a a cover for operations by Turkish special forces. Earlier this week it was reported that Turkey had allowed some 350 fighters to cross the border into Syria. Who these "fighters" are is anyone's guess. And it's hardly surprising that Ankara would flood Syria with new waves of fighters: If the Turkish-backed "moderates" lose Azaz, it could be the knock-out punch to Ankara's ambitions in Northern Syria. The situation as it stands now: The green represents terrirtory held by the "moderates". The Kurds (yellow) have made huge gains in the last week, while SAA forces are creeping up from the south As this map shows, Turkey has continued its UN-condemned shelling of Kurdish positions (represented by the blue rockets on map). For now, Turkey and Saudi Arabia seem unwilling to commit to a direct invasion -- so they're just doubling down on the same strategy they've used since the beginning of this conflict: Send in proxies. With Russia now openly supporting Kurdish forces, it will be interesting to see how Turkey's proxy army fares against Russian airstrikes. | Low | [
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The USDNGN increased 0.9000 or 0.29% to 306.4000 on Wednesday October 24 from 305.5000 in the previous trading session. Historically, the Nigerian Naira reached an all time high of 365 in August of 2017 and a record low of 0.53 in September of 1980. The USDNGN spot exchange rate specifies how much one currency, the USD, is currently worth in terms of the other, the NGN. While the USDNGN spot exchange rate is quoted and exchanged in the same da... | Mid | [
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"THE YEARLONG ROAD" "This is a story of one of many roads that cross the earth:" "of the pain, hopes, joys and illusions that spring from those who build them." "The authors wanted to tell it with the spirit, symbols and moral of a fable, to be able to embrace more freely a horizon of common sentiments for the majority of mankind." "You're still at this point?" "Now what?" " Next time you stop first." " Where?" "What's the rush?" "Are you trying to catch a plane?" " The road is for all, ya know." "You know that mine is a public service with the highest priority!" "Public service!" "Go throw your service in the river!" "I'd like to.. with you in it." " I'll report you!" "Our tobacco is here." "Easy, granddad, careful." "I have some." " These ones are leaves as well." "What's happening?" "Did you see.." "anything new today?" "What's there to see, Gregorije?" "It's been five months since I returned and I always see the same things." "Stones, windmills and sheep." "What's he doing?" "Among the people in all parts of the world, for every effort that improves the lives of others, someone has to pay first." "They are the men of good faith." "Their efforts should never be silenced or forgotten." "To this kind of people belong Emil and Agneza." "They also have tools." "He found work." "They're going to Baron Jacoviello." "I'm sure they're fixing his country house." "No, no, four days!" "I've already done them myself last month." "Then where's he taking his whole family?" "I get it!" "They have begun working on enlarging the cemetery." "They postponed that." "Who would've ordered it?" " Work for his kids but not us!" "He was acting very mysterious yesterday." "Why did they stop here?" "Are they watching us?" "They're talking among themselves." "But.." "You'll see.." "in a bit, they'll come down here and start working with us." "Those don't really care about anything!" "You don't know them." "In their place, I'd be doing the same thing." "Work creates envy." "When it comes out that it's all a hoax, we'll be in trouble!" "I'd be happy.." "if only twenty of them came." "Let's start!" "Ah.. they're looking for worms for the chickens." "They don't have any chickens." "This I know for sure, they live next to me." "# A lost sheep.. #" "You sing too!" "They're singing too!" "If they're singing, somebody has got to be paying them." "# A lost sheep.." "the ram has left me.. #" "Want to bet this time they're finally beginning work on the new road?" "And so, he's taken the measurements." "Ah-uh!" "That's too big a job." "They wouldn't have given it to just one man." "To save money, this country is capable of anything." "I don't want to get mixed up with this." "Let's go talk to the mayor." "The mayor left this morning." "So who's in charge then?" " The deputy mayor." "Then let's go talk to the deputy mayor." "Are you leaving me here?" "Wait for me." "Bernard!" "Oh, people, people!" "Do you see that?" "You thought they would come to work together with us." "Instead, they're going to the deputy mayor." "That one'll call the guards right away!" " Stop it!" "Even if the guards come, what does it matter, what could they do us?" "You know what the law says!" "Without permission, you can't do anything." "Nobody ordered you to do this job!" "There'll be a scandal, I'll be so ashamed!" "But I'm ashamed more to live without working!" "This is Scandinavia, you won't forget it:" "It has the shape of a dog." "What is it?" "What do you want?" "Just a word, Sir." "Dad, I'm over here!" "Silence, silence!" "But where do you think you are?" "These matters can't be dealt with here." " The mayor isn't here, he's always out." "It's useless to come to me." "I don't know anything and I don't want to know anything." "I can only tell you that the town never ordered any work." "Then, what are they doing, Sir?" "They who?" " Cosma, Emil, son of the late Nokiakova." "Tell them to bring their children to school!" "Today I'm teaching the War of Independence." "Nobody should miss it!" "Do you remember when I taught the War of Independence to you?" "I remember the war, Sir." "What I don't remember most is the last day I actually worked." "Winter has always been like this, since the world began." "And what can you do?" "It's an incurable disease, like cancer." "Come, you need to resign yourselves." "The most beautiful story I know.." "is the fable of the grasshopper and the ant." "It teaches sacrifice, good sense and reason." "We need to store in the summer.." "so we'll not starve during the winter." "Go now." "Go now, boys." "Go on, ask him." "Emil!" " Huh?" " You can tell me." "Who ordered you to do that work you're doing on the road?" "The Town." "But the deputy mayor denied it." "He said the Town had nothing to do with it." "Let him deny it." "But if he denies it, who's paying you?" "The Town, Bernard!" "What would the Town say.." "if me.." "and Angela worked with you?" "I'd say they would be pleased." " But Bernard, aren't you going to America?" "Yes, but the passport hasn't arrived." "In the meantime, I can work." "You know what this one wants to do?" "To sell my land for a ticket and leave me here." "Don't you understand Bernard can send for you later?" "Is it my fault the money from the land isn't enough for tickets for both of us?" "Emil!" "What is it?" "How much does this work pay a day?" "Forty dinars for you and eighty for Bernard." "120 dinars a day!" "What did you agree for the kids?" "But.." " For the kids, twenty." "We have no kids." "If only we had some, we'd get more money." "You see, having kids can come in handy!" "Of course, if this work lasted for.." "three or four months, then.." "What do you say, Emil, can one hope for that?" "We can make it last as long as we feel like." "If grandfather Gregorio were younger, he could earn money too." "We'll go to America." "We have it all figured out." "With the money we'll get from the land and working, we can buy the tickets." "Emil!" "Are you sure that this work will last awhile?" "Yes, it'll last." "I don't know what to think of it." "Why them and not us?" "I'm telling you, they're lying to us!" "We were here all day yesterday wasting time and they never said a word to us." "That's not how to behave!" " They've sucked up to the mayor!" "But how are they supposed to make a road with so few people?" "You do what you like, I'm going down to work!" " Me too." "Let's go see, Emil is my friend." "Good morning, Emil." " Good morning." "It's about time this road was done." " Yeah, yeah." "Hurry home, get a pickaxe!" "I'm sure they'll let me work too." "Let me help you, Agneza." "Give it here." "Let me earn some money too, Emil." "We've been unemployed for many months." " I'll sign you up." "You dig, I'll take care of the rocks." "This pole needs to be moved." "Three meters back, come on!" "Enough, enough!" "Enough?" "What about me?" " Emil, we're related!" "You're too many." "Sit down, Emil, sit down." "You mustn't, I'm tired." "I'm not giving you anything on credit." "It's been two months since you paid me!" "In a little bit, I'll be able to bury you in money." "How do they pay us?" "Once a week or every fortnight?" "Every Saturday." " Why do you ask?" "Why not?" " Is it possible to get an advance before Saturday?" "At first, you must make do for a while." "When all is settled, everyone will give you credit." "It's better so!" "They have to go by the rules." "Here's to the most beautiful road in the province!" "To your health, Emil!" "To Emil..!" "Emil, you are a friend!" "Good evening." " Come in, come, Emil." "You're here before me." " No matter, you go first." "Emil, dear Emil!" "You know, the sardines came in." "I was just waiting for you to open the box." " No, no, thanks." "I just want a kilo of bread and three ounces of cheese." "But why?" "You've eaten cheese all year round!" "You want to save money on a day like today?" "I'll put together something for you for tonight." "Hold it right there." " What is it?" "Wait a sec." "We've been looking for you for an hour, you must come with me." "No, I don't have the time." "I have to go home." "Bye." "Come on, let's go!" "Don't be afraid!" "What must I do?" " Be with us for a little while." "But my wife is waiting." "At your age, I only looked at myself in the mirror on Sundays." "If I don't do it now, I won't have any time to when I'm married." "Nice way to enter!" "How many times do I have to tell you to stay away from my daughter?" "Tell them that you've signed me up to work on the road." "Filomena, now that I have work, you must give me your daughter." "Listen, six months of engagement, then I go for one year of military service." "In the meantime, prepare the paperwork and when I return, I'll marry her." "Let's go." "If you don't give me to him, I'll take him anyway!" "Emil, I have one thing to say." "Before you begin, I have to tell you that we're already fully booked." "Nothing doing, not even for a friend like you." "What are you thinking?" "Like I want to get back to bricklaying!" "Water under the bridge, I don't do that anymore." "Come, I have a surprise for you." "Let's see for a second.." "These are really good: they keep the the feet warm and last forever." ""Special quality"." "What size shoe do you wear?" " The biggest." "Now that you are working, they'll be more useful than bread." "Can we get anything on credit too?" "Come on, come over here." "Susanna!" "Susanna!" "Mario, go call your mother." "She reads.." "reads all day long." "What you see is at your disposal!" "And if you don't like any of this, I have some new stuff down in the city." "We just want American stuff." " Original!" "What is it?" "Don't you see?" "See to what they want." "You could help me sometimes." "And throw away that cigarette!" "She smokes more than me." "I always keep them out for you, in the kitchen or under the bed." "Emil, sit down, try on the shoes." "Here's a cigarette." "Let's celebrate the new road." "I like a woman who smokes." " Did you see the way she stares?" "Who's she staring at?" "At me, dummy." "Can I try these pants on here?" "No." "But over there's a mirror." "I'll get undressed here, I'm not shy." "Do I embarrass you, ma'am?" "There, we're done." "Why don't you ever show yourself?" " But how can I?" "I have so many worries." "What worries?" "Now with the new road everything'll get better, you'll see." "It suits you." "Susanna!" "Bring Emil a glass of wine." "Do you feel like another?" "If the price is good, I'll buy this." "Do you answer for those guys?" "You never know, they're young." "How do I look?" " You look like an American." "If you could get the other workers to come to me," "I'll give you some stuff for free." "Get home, get home.." "My dear Emil.., tonight you're staying with your Agneza, upsadaisy!" "Antonio!" "Don Antó!" "Antonio, listen to me." "I made it all up!" "Excuse me." "Bless you!" "Don Antó!" "The mayor didn't order anything!" "I fooled everyone!" "Big Mouth!" "You're always with easy girls." " You're a real gem, don't forget me!" "# J'ai deux amours, mon pays et Paris.." "Par eux toujours.. #" "Emil!" "You must believe me, Big Mouth, I thought it'd be something else entirely." "I thought.." "that after me there'd be a dozen at most." "It's true, we are many, but I'm better than everyone!" "Parlez vous français?" " Me?" "Quatre années in France, four years in France." "Marseille, Toulon, Bordeaux." "I did everything," "I've even been a sailor." "What a life, always in the middle of the fish!" "# Paris, je t'aime.. #" " This one I don't know." "# Je t'aime, je t'aime.." "avec ivresse.. #" "It's not true that the Town gave the work." "I had a moment of despair, understand?" "Women suffer when they see that the husband has no work." "Les femmes!" "You're telling me!" "I've had twenty women." "Not one of them stayed with me." "Now in Marseille, I had a black woman." "Really!" " But how could I take her with me?" "Can you imagine a black woman here!" "No, never." " She would've suffered." "Bless you, Emil.." "you get to go home." "There your wife waits for you, who loves you very much." "Emil, one of these nights I might die." "Dead!" "But who would even notice?" "Do you understand?" "To die like a dog!" "I want to cry, Emil." "Let me cry, Emil." " Go ahead, cry." "You have to cry, cry!" "You know what, if I were a woman," "I'd work for you." "No, no." " Yeah, yeah!" "The Mayor!" " Oh, God!" "You're back at last!" "Viva the Mayor!" " Let's go to sleep!" "Hurray for the Mayor, hurray!" "I never voted for you!" "Jamais!" "And I'll never vote, jamais!" "Je suis Anarchiste, moi!" "I never vote on principle." "But you.., you're a saint!" "I kiss your hands." "Long live the road!" "We've already done 20 meters." "What is he saying?" "Twenty meters of what?" "Go!" "Emil!" "Emil!" "What were you doing?" "Why have you come back so late?" "The mayor's back." "Tomorrow the bomb goes off." "Aren't you happy?" "It's what you wanted." "Don't leave me alone now, if you do, I'll lose heart." "Did they eat?" " Yes." "Look at how many things I brought." "Come, eat something." " I don't want anything." "There are.. there are sardines." " No, leave me alone." ""Leave me alone.."" "The chisel?" "Where did it get off to?" "How many times must I tell you, that Ivo can't play with it." "How long it was since I used these tools?" "I even forgot how heavy the pickaxe is." "It's no use: when you're working, you feel like a different man." "There we go!" "Behave yourself!" "You know what?" "Sometimes we imagine things are uglier than they are." "It may be that things will work out." "I bet the mayor will consent." "Deep down, he's a good man." "You think everybody's good." "He'll send for me, find the money.." "and even thank me." "That's fine." "Let me sleep now." "My Agneza.." "Just think of it.." "at least we'll have peace for one year." "Yes." "But remember, this is last time I believe you." "Tonight, you turn me on so much!" " Take it easy, we'll wake the kids." "Here, take it, Mr. Mayor." "Long live Louis Salinas, Mayor of the new road!" "Hooray, hooray!" "Hooray!" "Mr. Mayor, my son thanks you for the construction of the new road." "But no, what are you doing?" "My son-in-law, Mario Dago, was for months out of work." "He kept me company, but I give him to you as a gift all the same." "Assistant!" " Yes, sir!" " Come here!" "Gather all this stuff.." "and follow me!" "Did he get offended?" "The Town did not order anything!" "You did this on your own initiative!" "If the Town had the money, it would've done the road a long time ago." "This would take millions!" "You must understand!" "What can I do about it?" "I tried all I can, but if the government has taken measures and won't help us, we must forget about the road!" "You sent your elderly to give me gifts." "Well, you can take them back!" "I never took gifts from anybody, and this you should already know!" "Whose is this?" "Take it!" " It's mine!" "And these?" "Even you, Donato, who's always had a good head on your shoulders!" "You wanted to send us to jail?" " I should've stayed home!" "Were you laughing at us behind our backs?" " Con artist!" "I wanted to show you how to live!" "This is a cuckoo's nest." "You think only of yourselves!" "Only of yourselves!" "Tremble over your poverty, for fear that someone touches it!" "When one is alone, one can crack a walnut." "But if we want to build a road, we must be many!" "Only if we're able to come together, can we achieve something." "Do you see where we're at now?" "It's not over, if we keep on working." "And who can stop us from continuing?" "Emil is right!" " We mustn't be afraid!" "I want to work!" " Me too!" "You hear that?" "And if you don't think so, it means you prefer to do nothing!" "You say that to me?" "I've worked all my life, con artist!" "I'll kill you!" "Emil!" "Dad!" "Ivo!" "Dad!" "Ivo!" "Ivo!" "Doctor, tell me the truth." "Will he become an invalid?" "It's a bad fracture." "He broke his femur, he must be brought down to the city right away." "I can't operate on him here." "Thank you." "Go slow!" "Go slowly, please." "Dad!" "You have a fever." "We have to keep on with the road, now more than ever before." "TOWN OF ZAGORA, ROAD CONSTRUCTION" "In the mountains, the winter is very hard and when it arrives, men have still more need to huddle together to find warmth." "Here we tell you how they lit a great fire to warm themselves:" "Big Mouth and Katarina." "Are you all here?" "Now, first team on the right." "Second on the left!" "Third team at the end!" "I'm against discipline." "However, when you need it, you need it." "See, now we're being smart." "By God!" "When news of this gets to the city, who gets dragged in the middle?" "Me." "They send an inspection, they hold me responsible and I get kicked out!" "A stroke of charity would suffice.." " Yes, and we make up the congregation!" "Don Remi, you've received enough charity from us." "Fine, but why don't you employ someone in your warehouse?" "Or in the office?" " They're all illiterate." "My work is very delicate." "My brother is right, we've already given way too much charity." "Every month, 1,000 lire for the Daughters of Mary, another 3,000 for the Orphans of St. Anthony, and 12,000 for the fund parish." "Couldn't you have work done on your building that's falling apart?" "Who said it's falling apart?" "And even if it is, nobody's touching it." "It's a national monument." "The Town must think about the citizens." "It's not our business." "The Town?" "Want me to tell you what the Town's budget is?" "Here you are:" "Revenue: 7 and a half million." "5 million for the duty contract that benefits you." "Aside from your business." "2 million for the rent of the woods that benefits you, dear baron." "Half a million for the family tax." "Outputs: 8 million, that are for the salaries of the town employees, the school, medicines and surgery." "Of course, if everyone paid their taxes as they should!" "Why bring up taxes?" "We didn't come here to be insulted!" "Everyone knows that with the taxes, you do as you please!" "Who is it?" "Have you finished?" "It's been an hour." "But don't you see we're still talking?" "What's that?" "Stuff for the town." "They are the construction records." "It's all there: hours of work, attendance, absences, family allowances, contributions, overtime, all." "Take it away, I won't touch it!" "Louts!" "They go, they come, they enter, they leave." "They were the same in school." "This is anarchy." "But what is happening?" "This was always a peaceful village." "Nobody ever complained." "Who could've put them up to this?" "This can't go on like this." "I already gave 120 kilos of pasta, 3 sacks of flour, 400 kilos of bread." "And who told you to give it to them?" "But who has the heart to leave his town without food?" "I couldn't deny them credit just right now." "You had no trouble denying it before." "Why don't you admit that the road would help your business!" "You too." "That's why you gave them the stones." "If I didn't give it to them, they'd go on my land and take it for free!" "It's been two years since my quarry closed!" "The government will have to pay." "They helped us so many times before, why shouldn't they help us now?" "Yes, for the cost of a public toilet, but this is the construction of a road!" "They're doing it in defiance of the law." "And all of you.." "are supporting them." "That's not fair!" " One moment, I didn't say that there mustn't be a road, but in compliance with the law." "There's only one way out:" "Call the police!" " No.. no.. no, never that!" "There'll be a scandal!" "I want to avoid a scandal." "You are weak!" "You don't want to lose your positions, but things will get worse." "You only look after your own interests." "Hypocrites!" "Sooner or later, they'll give up." "There's no need for the police." "They won't be able to deal with all the difficulties they'll have to face." "Here we go." "We are here." "Tomorrow we'll attack this curve, then there's this level part." "In a couple of days we'll have it fixed." "The Town announces that it will not pay for any expropriation to farmers in the case that their land is expropriated, or other properties of any kind." "It declares officially that it will take no responsibility for any expense that concerns the road." "Because this construction is both an abuse and illegal and done completely without the authorities' permission." "Work, keep on working!" "Now what?" "Now we go on like before." "Now even the stones know that nobody's paying us." "But how will we handle the farmers?" "When they come, I'll talk with them." "What is this X here?" "That's the cemetery." "Look, it's over there." "OK, but who's this in front of the cemetery?" "It's the house of one whose husband's in America." "For about five or six years." "A certain Katarina Pancrazi." " Ah, her." "That house has to go." " But.." "But how do you go to one and say:" ""Please, may I blow up your house?"" "Katarina would've heard the announcement." " You think so?" "The crier was loud and clear:" "lands, farms and all other property." "Then let's move the cemetery." "Now you want the dead to be against us too?" "No way, the dead shouldn't be touched." "If we take the land from the living, why can't we take it from the dead?" "That damn Emil really has left us in a heap of trouble!" "But when has a worker ever been sick for a week straight?" "Why, am I not good enough to fix our problems?" "If you didn't trust me, why did you make me boss?" "You made yourself boss, we didn't do it!" " That's right." "But there's Emil!" "Morning, Emil!" " Morning." " Morning." "Emil!" " Thank goodness you're back!" "That Big Mouth is terrible." "He wants to move the cemetery and blow up Katarina's house." "We can't work with him." "If you don't come back, we're leaving!" "You should've stayed at home, you'll just get sicker here." "I couldn't stay in that bed anymore." "Do you see how good the road's going?" "And look what I'm doing here." "See." "With these the ground'll be as smooth as a billiard table." "Where did you get all this wood?" "Angela!" "Dad!" "You could at least shave!" "Mom has written." "They put Ivo in a cast." "The doctors say it'll be a long recovery." "But will he heal?" "We don't know." "Mom says she's found work at the hospital." "That way, we can pay for the treatment." "Take it." "Make her understand that it's for her benefit." "She can make a profit." "The price of her land will rise with the new road." "If she brings up the announcement?" " Tell her that it's not true." "But.. this is crazy." "Yesterday, the mayor came to offer me jobs for 20 people." "Ah, then there is work!" "Yeah." "But only if we forget about the road." "Are you crazy?" "We won't be able to do it." "You heard the announcement." "They say that the farmers want to come here to kick us out." "Let them come, let them come!" "Today an announcement, tomorrow something else.." "and when will we finish it?" "You think we should refuse those twenty jobs?" "That's money." "At least those 20 will be able to keep going until Easter." "And who said, you have to refuse?" "Let 20 go there and let the rest work on the road." "Yeah, but it wouldn't suit the mayor." "Did it suit the Town when you started working on the road?" "And you see, they've already found twenty jobs." "I don't understand anything." " Yes, you do, Emil!" "If they offer us 20 jobs, then now is the time to continue." "Today it's 20 places, tomorrow it's everything and bing, bang, boom, they pay us for the road!" "Attention, attention!" "Listen to me!" "You should know that we've already achieved something." "And this is thanks to Emil." "He spoke with the mayor." "He's offering work for 20 people, pay upfront." "What kind of work?" " For how long?" "It'll last for a few months." "You'll have to do a little of everything:" "Repair our bell tower, go into the vineyards, clean the rows.." "Draw your names together and give them to Emil." "And so?" " She says we're crazy." "She says that the house is hers and she won't give it away to anybody." "But did you explain it clearly?" "Make her understand it all?" " Yes." "The Town crier explained it much better than we." "Want to know the truth?" "I think Katarina is right." "You'd blow up her house?" " With nothing in return?" "Nothing in return?" "Then you agree with the Town." "They won't give money to us and yet they'll give it for a house!" "I know who I'll send to her." "I'm always at the same place." "If there were only two stones alike!" "They're all different from each other!" " Don't get discouraged." "I'll never be able to learn a trade." "Look how Dad does it." "He's been doing it for 20 years and you think you'll learn it in a few days?" "With stones, one can read them like a book." "Here, look." "They also have their veins, like Christians." "To split a stone well, you must strike the largest vein." "Just like that." "An art is an art." "I've got a job for Lorenzo." "Come here a sec." "Listen.." "Do you see the vein?" " I don't see anything." "It's been six years since she's seen her husband." "You understand ?" "Fine." "Did you really have to send him to her?" "Who else then?" "Those ones." "But have you seen their faces?" "They look embalmed!" "See what can happen to a woman alone when her husband goes off to America?" "What are you looking at?" "Where you taking me?" "Hush." "Come on." " What's got in your head?" "Tonight, not now." "I'm tired at night." "As soon as I eat a piece of bread, I fall dead on the bed." "How beautiful you are!" "Beautiful!" "Let's have a baby." "You know that we can't afford it." "But if we don't have children now.." "How can we feed them?" "How?" "What's a woman without a child?" "Let's have a child, Bernard." "Just one!" "So, if you do go to America and I can't come at least I'll have someone." "Mom, Dad's come back!" "Dad, stop!" "Dad, wait!" "What did you bring me?" "I came here to see if anybody would give me some money, but they still can't pay." "You were beaten?" "Who had time to talk?" "She's a tiger!" "If you got hurt, that's a sign you should leave her be!" "I barely even saw her!" "Big Mouth!" "Big Mouth!" "Here comes the farmers!" " What, where?" " Down there." "Work, come on, work!" "Stop!" "Let's talk first!" "Don't do it!" "Let's reason this out!" "Stay calm, don't move!" "This is our land and nobody's to touch it!" "You want to ruin us?" "A half a meter of land never ruined anybody!" "You can't bully us!" "Do you know what the land means to those who work it?" "A piece like that produces at least 200 kilos of potatoes in November and 300 in October." "Look!" "I'm a farmer like you." "Here we found only stones, no potatoes." "And suppose I give you the land, what can you give me in return?" "The Town will pay." " What Town?" "Didn't you hear the crier?" "Sooner or later they'll have to pay us and you." "Liar!" "You just want to cheat us!" "Don't you understand that the road'll be good for you too?" "That when it's built, the trucks can come to the fields to load the olives?" "No one gives away land!" "If we extend the road, each of you will lose half a meter of land." "But how much do you gain if the trucks come to load up here?" "You're spared labor, time, effort!" "If we continue to do the math, it'll wind up with you paying us!" "The foremen inform the entire population and the town authorities that the farmers, instead of keeping the land, have given it to us as a gift to enlarge the road." "For this reason, the foremen express their deep gratitude to these deserving people." "# So many people," "I sent to you." "I received no answer." "In your bosom, lady, a heart of Judas." "In your bosom, lady, a heart of Judas." "You've deceived me and made me cry. #" "Katarina." "Mrs. Katarina!" "A good nap, eh?" "You're another one of those." "You come at this hour?" "Take off your hat!" "You're not at home." "This morning an infant and now one with a mustache." "The building must stop because of your stubbornness?" "Don't yell, you'll wake the baby!" "Today you've made a procession." "In any case, I'm not giving you the house!" "It may be a hovel but it's my home and I've nothing else." "Now, get out!" "I won't move from here till you hear me." " But how could you even imagine it?" "You, that look like a family man, go and explain what a home means to those bums." "They are not bums." "They're doing a good job for all as well as for you." "For me?" "Nobody has ever done anything good for me." "Beginning with my husband, who gave me two children and then went to America." "Forget about America, we're talking of the road." "I like the road the way it is." " What do you mean?" "So much so, that I'm going to walk on it now." "Wait!" "Stay and hear me for a moment." "They call me Big Mouth, but you won't let me talk." "I have no time." "What are you going to do with that?" " I'm going to cut wood." "Hurry, hurry up, it's late." "Just at this time, you must cut wood?" "I have other things to do later." " Let's rest for a moment." "I can't take another step." "I didn't ask you to come." "How much will you get for all this work?" "250, plus an extra 30 now that it's winter." "How do you manage to get by?" " I don't know." "At first, he sent me something." "Ten dollars a month." "It's been two years now since I received a penny." "Meanwhile, the children grow up, you have to feed them, clothe them, send them to school." "And who knows where he is." "The last letter he sent was from Detroit." "That's the advantage of being born now." "They want to leave.." "leave." "Leave your wife, leave your family." "I have no one." "I'm an orphan." "When I can do no more, I get up and look for work far away." "Do you know I speak French too?" "I have two sons, but I'm happy all the same." "I may be poorer than St. Francis, but I'll always find money to raise my kids." "Who knows how I'll do it?" "Yeah." "Who knows?" "There's the road." "It's twice as it was before." "Come on, let's go!" "For years, I wasn't so happy to be working." "Do you know, if it wasn't for the road, at this time, I would've already went away to other parts." "I think you're really nice." "Katarina!" "Why don't you come to work on the road as well?" "Women get 600 lire a day." "When do they give it to you?" " Soon, soon." "And for you, for you we'd pay for the house as well.." "in other words if.." "I must be sure of the money, I can't put myself at risk." "Wait, I'll take the ball." " Let's go there, on the grass!" "Come on, hurry!" "Today, I'm really hungry." "Shall we eat together?" "No.. if I'm not alone, I can't eat in peace." "May I?" " Who is it?" "A little surprise." "Morning." " Morning." "I have two eggs to be cooked." "May I come in?" "Please do." "Give it to me, I'll cook them." " Just give me a pan, I can do it." "There it is." "Filipo, Mariza!" "A little bit of oil, eh?" " Go ahead." "The other night you left your guitar." "I didn't know where to bring it." "The kids might break it." "For heaven's sake, without a guitar I'd feel naked!" "Écoutez.." "French." "I wanted to come to pick it up, but I don't like bothering people." "Eat if you like." "I look like an old maid!" "Let's go." "Since my mom died, I haven't been able to eat a good broth as it should be made." "What's the big deal?" "Just heat up a bit of water and the meat jumps right off." "I have no patience." "Do you know who that is?" " No." " That's the one that sets off bombs." "How come I've never seen him before?" "What class was your husband?" "He was of the 18th." " Oh, I see!" "When I got back, he was leaving." "Then the war broke out and goodnight!" "Eh, we're old, the years go by." "Do you know that.. do you know that I don't even remember you?" "What an idiot I am!" "When I was grown up, you were still a girl." "Do you always drink like that?" " Yeah, I beat everyone at it!" "A man who drinks too much for me is not a man." "What, you don't like a man that drinks?" "No." "When he drank, there was thunder in the house, everything went flying." "I don't!" "When I drink," "I fall in love." "Big Mouth!" "Big Mouth!" "Shoo, shoo!" "Big Mouth." "Hey, Big Mouth!" "The others have already started to work." "You had to choose my bed to rest on?" "Excuse me." "I haven't slept so well in ten years." "Katarina listen:" "I dreamt that your husband was dead." "Bad grass never dies." "Katarina, I.." "Yeah, yeah, go on, they're calling you." "Tonight, I'd like to show you my house." "I have an idea.." " Fine, fine." "Let's meet later in the field." "My house has many advantages over yours, Katarina." "As busy as I am, sometimes I don't even sleep here." "Houses are made to live in." " That's why I don't want to knock down mine." "But you would make this into a real house." "Look here." "Here you can put your animals." " I don't just have animals." "The children over there." "Here's where you can sleep." " Oh, you have wine there instead of saints." "It'd be too much of a sacrifice for you." " What sacrifice?" "Sooner or later the Town pays." "I give you my house and you give me the bond that's due to your home." "When the Town pays, I'll grab some money and go abroad." "I've gotten very bored staying here.." "alone." "Did you have to wake me up at this hour?" "If we don't do this now, she'll change her mind and stop the road." "A la guerre comme a la guerre." "We'll settle later, eh?" "Get out of the barn and take away the beasts!" "Oh, my husband!" "Have we forgotten anything?" "Not a thing, don't worry!" "You won't need the wood and straw." "Here, however, will be a blaze the whole countryside will see." "All will know of your great sacrifice!" "May God forgive me!" "Was this madness really necessary?" "Aren't you glad, we're changing house?" "You hush!" "I told you I let you stay only if you were quiet." "Oh!" "Let's go ahead." "Here's fine." "You two hide behind the wagon and don't move!" "It can be dangerous." "For heaven's sake, stand still." "Couldn't you do it with a pickaxe and ropes?" " You'll barely notice it." "Only one blast and no more worries." "How many things have happened here." "The marriage, children.." "I got it." "There." "But, where will you stay?" "I told you, I'll sleep at Emil's until his wife returns." "Go!" "Just like that." "God!" "Let's go." " No." " Let's run away now!" "Come on, let's run!" " No!" "Don't think about it anymore." "Why?" "Attention, attention!" "The complaint is clear." "Starting public works without permission from the Town authorities." "Illegal removal by means of mines of a house located near the cemetery." "The house was blown up with my consent." "I'll do as I see fit with my things." "With your things, yes, but not with a mine!" "You could've hurt some poor person." " We did everything responsibly!" "Nothing happened to anybody!" "You need a permit to use mines, and you neither had one to own or use them." "Nor did David Lena who gave them to you." "I built it myself." "I have here a list of those who have caused these disturbances:" "Cosma, Emil." "Lena, David." "Garri, Bernard." "Paternost, Donato." "Prast, Frano." "Bocca, Antonio." "Vertin, Carlo." "Come with us!" "What about me?" " You're a boy!" "Come on, hurry up." "Renata!" "Go to sleep at Angela's, don't stay by yourself." "It's my fault, I shouldn't have listened to you." "No." "Wait for me, Katarina, wait for me." "What will they do to you, Bernard, what will they do?" "It's probably a mistake, you'll see, they'll release us tonight." "Already, spring announces itself with its perfumes and its sudden downpours." "The men, cast down by what had happened, and the threat of jail over their heads, hardly leave their houses." "The land seemed inhabited only by women." "I take advantage of her father's absence and have her leave." "What else could I do?" "At least, she can put aside a few coins for her trousseau when she marries." "It's not shameful to be a maid in the city." "Now you come?" " I had stuff to do." "I'm sorry to leave, but five or six months will pass quickly." "You'll wait for me, right?" " But what will I do?" "When you come back, I'll already have left to be a soldier." "Then we won't see each other again?" "If I leave you free, who knows, you may find in the city one more serious than me." "One that has a job.." "I'm not good for anything." "Don't you see, they should've put me in prison?" "You talk like this ever since she has come around you." "You think I don't notice?" "Speak quieter, they can hear you." "I don't care if you go with her, even though she already has a husband." "Just be careful." "If David realizes it.." "What do I have to do with it?" "It's she who looks at me." "Don't cry." "Else, they'll think I've beaten you." "I'd like to leave you, because I don't want you to suffer." "I'd suffer more, if you let me." "But in the city there are so many!" "But I can only think of you." "Damn!" "Why was I made like this?" "At least, I could come to the city to find a job too." "Listen." "When you are a soldier, couldn't they send you to where I am?" "Heaven knows where they'll haul me." "Here, wear it on Sundays." "I recognize this, you know?" "It's your father's." "Really, have you forgotten the Hail Mary too?" "We can't pray anymore, our minds are elsewhere." "Come with us, you must help us!" "Let our men go free." "Our houses are empty, we no longer live in peace." "What have they done wrong?" "Is it a sin to work?" "We've always been good Christians, you can't abandon us now." "Let them come home!" "Good morning." "I'll have a little fun here." "Let me borrow it, so I can play with my friends." "You can keep it." "Go on." "He gave me the ball!" "The game made me thirsty, do you have some water?" "Stop it, let me go." " Wait till I tell you.." "With the door open, I can't drink." "Now's your time to learn." "Fine." "Don't you get jealous thinking of Rosa and all the young men in the city?" "Not at all!" "I only became engaged to Rosa on a bet." "Why?" " In order to spite her mother who didn't want it" "Your water is good." "Maybe because you drink from it too." "Where do you get it?" "Can I come too?" "At the bottom of the well." "When do you go?" "When there is none." "Before sunset, around five, six." "I don't like waiting in line." "He's good, leave him alone!" "Wait, what are you doing?" "They're children of prisoners, what can they learn?" "They'll come back to school, when you release our husbands." "We'll become an ignorant people, if you don't help us." "Let's go." "No.. not the children!" "It's about time you showed up!" "Did you forget you're our mayor?" "When you needed our votes, we were your children!" "If you don't release them, we're leaving this land right away." "Let's all go, this very day!" "We won't stay in a land where nobody wants to help us!" "Here we'll leave only the dead." "You'll be the mayor of a town of ghosts!" "We didn't put you in office to arrest our husbands." "Please withdraw the complaint, Mayor." "At least do it for our children." "It hasn't even been a week since Rosa left, and I'm already here with you." "Is she doing the same in the city?" "But you told me, you didn't care at all." "I have a weakness for women, you wouldn't understand." "I feel bad for her." "That's all." "But I do understand you." "Come here!" "We'd better leave." "Someone can come by any minute." "Wait." "Only now, you decide to be worried?" "If your husband ever finds out, he'll stab us." "Who knows when they'll release him?" "It's exactly that I can't deal with." "Him there and us here." "He wouldn't have such scruples." "I mean nothing to him now." "You don't know what he's made me suffer." "One time, he went away for six months with another woman." "One from the city, like me." "And you?" "At certain moments, I think I love him very much still." "But he changed when he brought me to the country." "Before, when we were engaged, he was a fine man like you." "He was working, he wasn't like this." "I shouldn't talk to you of these things, but.." "I'm fine with you here, believe me, but.." "I don't even know how to explain this." "Think about Rosa." "Don't worry." "Even in the city, girls like Rosa don't compromise themselves." "It's not just Rosa, it's everything." "What do you expect from me?" "I have neither skills nor talents." "I might become just like your husband." "Let's go." "Don't think about anything." "Do like I do." "Guess what, Bernard?" "I'm pregnant." "And now?" "Dad!" "Where's the baby?" " Waiting for you at home." "Did you sleep well at my house?" "Yes, but what about tonight?" "Where will you sleep?" "Tonight?" "Tonight, I'm grabbing myself one of those hangovers!" "Where's Mom?" "She didn't know you were coming home." "Look at the ball Lorenzo gave me." "Did they treat you badly?" "No, Mayor, indeed they ate every day!" "We didn't do this out of malice." "But you started blowing up houses!" "The Town should have blown them up." " Quiet." "That bend over there, shouldn't have been done that way." "It's too narrow." "He's right!" "The Mayor knows his roads." "I always said that he should be directing the work!" "The bend can always be corrected." "It just needs to go a bit on Baron Jacoviello's land." "Yeah.." "But you'd have to expropriate it." " Fine, we'll expropriate it." "But when you get to the river, there's also the bridge." "It'll be a tough job." "For us, nothing is tough." " And for the bridge we have him." "What about him?" "If David gives us a hand, the bridge'll be just like any other job." "At one time, he was in demand by the best companies." "The bridge is not a problem." "By this time, the road should've been done." "It'd be very easy for the government now." "We already finished almost half of it." "And they couldn't say no now!" "One more drink!" "And you, if you drink, will get taller." "I tell you that we must hurry instead." "In a couple of months, they'll finish the road and somebody else will get there before us." "But who?" "Look around you." "Who?" "They're all dying of hunger!" "Yeah." "But the wholesalers may come from the city." "And they'll organize for you the sale of olives, potatoes, fruit." "Look!" "Dad made it." "There, that's where I fell." "Yes, but now it is no longer dangerous." "Do you see how big and beautiful it is?" "We should go." "The train departs early tomorrow." "Will you come to me, Dad, when they take off my cast?" "But Dad must first finish the road." "Yes, yes, of course." "As soon as they give me my first pay, I'll come." "I'll pay the hospital and you can give up that job." "You're like a child." "Don't be so trusting, Emil." "We're poor, they roll over us as they like." "Wouldn't it be safer for you to go work in the country?" "The season will be good now." "The Mayor is with us now, at least you have to trust him." "I cannot resist you," "I have suffered too much." "I just get here and you.." "barely out of prison, start it up again." "As if we hadn't had enough trouble." "Did you come on purpose to fight?" "Let's not ruin this night we are together then." "Let's go home." "Now we need to get him a passport too." "Couldn't you have waited?" "If he's born on the ship, we won't have to worry." "Wait, wait!" "Are you crazy?" "Cover up." "I'll take that ladder and smash it." "Now you have to be careful." "If I fell down and died, what would you do?" "Should I leave?" "Yeah, go." "Now you can't go and work on the road anymore." "You have to be careful, and the work is way too hard." "Be we need the money, and it's for the ticket to America." "The baby's hope chest." " The hope chest already!" "But you see how many new worries are coming in all at once!" "Why get mad about it?" "I'm so happy." "How come we can't see anything yet?" "What are you doing?" " You're OK, right?" "You know, I would've waited for you even if you were in jail for 30 years." "I have to tell you something." "When we married, I didn't like you so much." "I only liked you when you laughed." "My Angela," "I only took you for that piece of land that was in your dowry." "But now.." "No, no!" "I want to see how my house looks with a woman inside." "Please leave, they saw you come in." "Do you want to compromise me?" "Katarina.., I would've liked you when I was twenty." "We'll have time to talk tomorrow." "It's late, go away!" "In prison, I thought only of you." "Be good, for heaven's sake!" "Please, get out, get out, please get out!" "Katarina.., where were you twenty years ago?" "Why didn't I meet you earlier?" "Would you have married me when I was twenty?" "I would've never let you go without." "If you want, I'll marry you then, as soon as I get the money for the road." "Don't say these things to me." "It only makes me despair." "Don't you think.." "your husband hasn't already taken another woman in America?" "Farmers are all alike." "As soon as they go abroad, they find another woman." "And that's why he doesn't write you." "If I'd left.." "I'd send you a telegram a day." "The years are passing, why do you want to waste them?" "When you take away love from a life like ours, what do we have left?" "All right, I get it." "Give me the guitar and I'll leave." "I can't talk with this wood in front of my face as if I were at confession." "Let me in for a moment." "I have to tell you something urgent." "If not I'll forget it." "I can't open it." "You know I can't!" "Who did you used to play with when you were a kid?" "How is it that we never never played together?" "What beautiful hair you have!" "Give me one of them." "# Katarina, Katarina.." "You are the heart of my soul.. #" "They released you?" "You're a bitch!" "You forget, don't you?" "For ten years you were the most envied woman here." "I gave you all, all!" "What more could I do than I've already done?" "What did you do?" "You've always taken all the lovers you wanted, yes!" "You've always done as you liked!" " Shut up, shut up!" "I want to leave, OK." "Let me!" "I stole!" "I stole for you!" "For me?" "You stole for yourself!" "You didn't go to work!" "Look at the others, look at Emil, look at Big Mouth: they're just as poor as you!" "Did they ever go and steal?" "Come on, come on, that's all you know!" "Mom, Mom!" "It's nothing, honey, it's nothing." "I'll stay here in the country because I've given my word." "But you watch out, don't let me see you again." "As if you've never seen me or known me." "Remaking the old bridge was the largest obstacle before arriving in the plain." "It was also the great attempt that all had been expecting from David." "Here come the leaders." "Good one, huh?" "Later, tell me another one!" "Big Mouth, is it true Katarina kicked you out of the house?" " Hello." "Morning, David." " We must level everything here." "We'll need to form a team of carpenters." "Me and Donato will start on the road after the bridge." "You can take the stones." " How come I get the stones?" "Only yesterday, I was your boss, you shouldn't treat me like this." "I've done everything myself so far." "What's this ingratitude?" "Emil!" " I'm right here." "I come on behalf of all the farmers." "There's not enough for the harvest, you need to give us a hand." "We can't pay you now, but we'll give you something." "Take twenty men." "Could you send us too?" " No, I need you." "We're going to need some young men." "He's right." " We'll begin right away." " Go, go." "If they make a monument to the road, they should put you lying just so." "I need to apologize for the other night." "I won't annoy you anymore." "It's the wine that puts bad thoughts in your head." "You shouldn't drink." "It's not the wine." "I'm always like that." "When will you return the key?" "What key?" " The key to my house, no?" "Seeing that things are this way." "I gave you the house cause I like you, but seeing that you don't want to.." "You're used to whores!" "What kind of job is this?" "I know how to do the other work." "A builder must be able to do everything, not only break rocks." "For the first day, you've done wonders." "Come on, by God, it's nothing." "We didn't need him." "I could've done it all by myself, you know." "Tonight I need a team to do a rush job." "OK, I'm there." " Me too." " What kind of job is it?" "I can't.." "I'm tired." "If Lorenzo's not going.." " Let's go." "See you tomorrow." "David!" " Huh?" "Don't you want to go to town?" " No." "With the streams one is never sure." "The scaffolding is still too weak." "I'll sleep down at the old mill." "If I'm not bothering you, I'll stay too." "I'm tired of sleeping at Emil's." "He's boring:" "He only speaks of his wife and work." "You're full of it like me, but you traveled too!" "Get out!" "Get out!" "What are you doing?" " No, Dad, don't!" "Go ahead." "What happened?" " Nothing, nothing." "He knows?" "He knows." "Go away, go away." " Go away, go away!" "What did he do to you?" "I want to know what he did!" " Go away!" "Nothing." " Leave my mom alone!" "I'll see you tonight?" " No." "But we need to talk." "I won't come back to the site." "Believe me, I won't anymore." "Look how unjust it is." "Two men, like you and me.." "to end up like this.." "without a home.." "like two orphans." "Old age!" "How do you like marriage?" "Does it suit you?" "I've never done it because the women need to be looked after." "But if I look after a woman, who's going to look after me?" "I'm spoiled!" "Eh, since she said that I mustn't drink, nothing, the wine stops here." "Let's go to sleep, go!" " I don't sleep." "Be it work on the bridge or love.." "I'm ready to drop from sleep." "Good night." " Good night." "Lorenzo!" " Lorenzo!" "We thought it over, we'll do that work." "Why not?" "What else can we do in the country?" "Fine." "Let's go." "We'd be cool if there wasn't a moon." "Even the moon looks like a stone." "Antonio says that it's inhabited." "He read it in the newspaper." " There'll also be military service." "If it's true that it's inhabited, then it'll have everything." "Just like us." "Cars, roads, bridges, wine." "Even women!" "Lorenzo!" "Would you like the strength to be able to split the moon with a hammer?" "Think how many women would fall on me!" "You cannot split the moon, but the earth, yes." "Seriously." "With the atomic bomb." "My boy, all it takes when they're testing it is to mistake the dose and everything goes back to before." "How was it before?" " What don't you know?" "Before the sea and the volcanoes were where they are now." "Emil explained it to me." " Why, where were they before?" "Somewhere else." "We lived under water." "He says that we weren't men." "What do you mean?" " We were fish." "Big Mouth told me that." "He heard it abroad." "If the war is being waged like before, you know how much work we'll have in this country?" " Why?" "We could manufacture cannon balls." "They say they're made of stone." " You've been hit too hard." "I think they won't call us to be soldiers anymore." "If they use bombs, what use would we be?" "Who knows how they make a million?" "Once, a friend of mine saw it." "He says it's paper." "I'm through." "A year ago we didn't even know how to hold a hammer." "When I come back from being a soldier, I'll make my own house." "Let's go." "Do you see?" "The farmers sent it to us." "And the wine?" "Is there no wine?" "David, take this." " I don't want anything from you." "Leave her alone!" "Lorenzo!" "Lorenzo!" "What happened?" " Leave me alone!" "Explain!" "I don't want fights at work." "It's his fault his wife gave him horns!" "Up until now, he's been a thief and now he comes here to play the hero." "Come on, Big Mouth, scrub it!" "I'm doing the laundry tomorrow, want to help?" "Get married, so you won't get pooped!" "I'd marry you, if you did my laundry every week!" "Where did you learn to wash like that?" "France?" "Be careful, you don't spoil your hands!" "Where are your women?" "If Katarina saw you, she would cry, poor thing!" "Do you know how to cook too, little lady?" "Tomorrow, I'll bring you an apron." "Trim your mustache, it doesn't look good on a lady!" "Show us that you are a man!" "What are you doing, are you hiding?" "How ugly you are!" "Ugly like a monkey!" "Wait, I want to sneak a look." " You crazy?" "Run, run!" "David, I'm telling you too, if she comes to work tomorrow, I'm out of here." "You didn't want the child earlier." "Don't you know something could happen to the baby?" "But what did your mother do?" "And mine?" "And his?" "They didn't stay at home." "They went to wash clothes, to pick olives." "They cut wood until the last day." "And we were born." "You must be the son of a lord, Bernard." " You see?" "You're old fashioned." "Has Rosa written you?" " She wrote yesterday." "I wonder why she doesn't write to me." "Do you write her?" " But I'm busy." "She's probably busy too." "Does she ask anything about me?" "Not even one word." "How am I, how I'm doing." "If the call from the army arrived." "What should I do?" "Write to her?" "You're asking me?" "You know what you gotta do." "Let's eat together." "Do it for the child." "You think he doesn't understand?" " Dad, I'm hungry!" "Sit down, I'll serve you." "It doesn't matter that you treat me like you did before." "I know that you suffer much, that's why I endure it all." "How's the bridge?" " I can't wait for it to be finished." "Then I'm leaving." "Dad!" "Mom wrote." " Really?" "Read it." ""My dear husband, I'm writing to let you know that in a few days our little Ivo will have his cast removed." "Hopefully he'll walk as well as before." "The doctors neither say yes or no." "My dear husband, if you were here, I would be more happy." "I'm worried for you, but I will always love you very much."" "Does she say so?" " Yes." ""I will always love you very much."" "Continue." ""When I receive a letter from you, I'm truly happy." "I feel like a girl again." "Write again, Emil." "And when you return home, let's not fight anymore, please." "Let's hope that all our greatest troubles end well for once." "Much health and kisses, Agneza your wife."" "She said, "Health and kisses"?" "No.." "Come on, let me see." "You're cold, I'll get some dry clothes." " No." "I'm going." "Dad, I'm coming with you." " Come on." "David!" "Go ahead." "Don't think I'm a coward." "I'm sorry for what happened, but I can't take this anymore." "Here!" "Kill me!" "Have you ever been to jail?" "I have." "I've been there, but always for little things." "It's easy, however, to stay there the rest of your life." "You see?" "Only a moment." "Then you go for twenty, thirty years." "And then.." "how do you kill another man?" "A little boy.." "like you, that still doesn't know what he wants." "Lorenzo!" "Lorenzo!" " Rosa!" "Rosa!" "Watch out for the boards!" "You mustn't return to the city." " I won't." "What did you do to your hair?" "Do you like it?" " No." "You look like a boy." "It's your fault." "You were always talking about city women." "All this time, I thought of you the way you were before." "And Susanna?" "I want to get married right away." " But you have to leave." "I will, but first I'll marry you." "They told me that you're leaving after the bridge is tested." " Yes." "But before I do, I come to speak to you to reach an agreement on all this." "I want to be at peace with you." "Where will you go?" "Far?" "Up north.., there's a friend of mine who has a business." "I wrote to him, he wrote back." "He said that he has a place for me." "A little work." "Enough to begin with." "Come on." "Don't cry." "You must find someone else." "I'll come every so often to see Mario." "You'll be better off." "These things happen and it wasn't your fault." "He's going to know whose to blame." "Is the testing dangerous?" "I hope not." "Good night." " Good night." "I'll tell you again, that thresher cost me two million." "Don't you forget that." " Be careful." "Nothing must happen to my oxen." " But what could happen?" "Nothing!" "It's a bureaucratic formality." "Hey, are you going alone?" "Yes." "Will the trucks be able to pass?" "If it holds a thresher, it may well hold a truck." "The critical point is in the middle." "It's going through right now." "My God, let's hope it holds." "Bravo David, you were just like Julius Caesar!" "Make way!" "Let's go." "Come and say hello to your wife." "Go on, David, embrace your wife, look how happy she is." "He still loves you." "The river was won." "David and Susanna left together for a more honest future." "But what fruits were brought by the summer sun to the men of our land?" "Here you'll see that to approach the sea, how necessary the goodness of one man is." "The state budget for this year has already been approved." "In the province, the whole country, there are so many other roads to do." "And then the government has the problems of pensions, war damage." "Speak out!" "Are they paying us or not?" "Tell us about the road!" "But the government has formally committed for the next year." "More couldn't be obtained." "Traitor!" "Cochon!" "Now we've finished the road, you're telling us there's no money?" "You knew there wasn't and you had us work anyway!" "That's how you look after us!" "You and the government wanted us to build the roads for free?" "I think it'd be good to resign." "We're fed up, go away!" "Never set foot here again!" "I ask the council here to please accept my resignation." "And what about me?" "Who'll give me back my house, huh?" "Who'll give it back?" "On behalf of the Town Council, I accept the resignation of the Mayor." "I declare the removal of his seat." " He should've been kicked out earlier!" "I think it was it all fixed!" "Surely, he was paid to act so." "It can't end like this!" "Open the door!" "They won't eat until the Town has found the money." "Who kicked them in the head?" "Where do they think they are, India?" "Sure, they're overdoing it, but put yourself in their place." "The few jobs of the season have already been taken by others." "If you take away the road from them, they go back to sitting on the bench." "Take it away, it's hot." " Doctor's orders:" "It must be hot." "Emil told me:" "they'll will die all together but at least you'll know why." "They really hope by making some noise, their actions will make the newspapers." "They want a scandal." "They are desperate." "Desperation has never done anyone any good." "Why do you go on so?" "My brother has nothing to do with it." "It's not your fault." "You mustn't worry." "Go to them, talk to them." "Today, you're no longer just their teacher, but their new mayor." "Bernard, Bernard, where are you?" "Are you crazy?" "Where's Big Mouth?" "Why isn't he here?" "Dad!" "Dad, why don't you answer?" "Antonio, get out now!" "Your daughter is getting married tomorrow." "Dad, I'm not getting married without you!" "Lorenzo is waiting for you to sign the papers." "If we want money, we must continue to work." "And if you don't come out, we'll have to go it alone!" "Open, open!" "Do you intend to stay down here much longer?" "Until the problem with the road is resolved, Mayor." "We need to make a scandal!" "Take it to the newspapers!" "This is the only way we can be heard!" "If it's in the papers, the government must give way." "Then I'm staying here too." "I will fast like you." "We'll see who has the harder head:" "You or me!" "My God, what are you doing?" "You're sick, you can't!" "Go, Matilda." "Go." "What are you doing on my land?" "I'm rebuilding your house." "I'm putting it back." "I was sure that the money was coming." " You found a good excuse." "You wouldn't know what to do without food and drink." "I'm fasting." "I drink water and nothing else." "Wine, I eliminated altogether." "There's Angela." " You see angels everywhere." "Agneza!" "You're back." "Must I always find you behind bars?" "And Ivo?" "Dad, I can run too." " Really?" "Go on!" "Come out." "Come home." "Let's see if you can listen to me at least once." "You can't leave them there." "Go there, convince them it's crazy and that.." "But think, Matilda, they're right." "They're right to want the scandal." "You can't work for glory." "I gave them the stones, the earth." " Millions and millions." "And I've fed them all these months." "I swear, if I didn't have this dilation of the stomach," "I'd be down there as well." "But you can't leave my brother there." "He's old, at least do it for him." "What do I care about the others?" "They can do what they want." "But him, he's very ill." "You know it!" "Who knows those that built this country how many days of work they got from us?" "Centuries." " But how?" "Centuries to make four houses?" "They weren't made all at the same time." "The first of our families.." "made the castle." "Those who came after made the church, and your grandparents.." "made the Municipality." "Even in ancient times, there were four pennies to.." "to make something in this country." "Eh, it's an ancient evil." "Then what are we doing in here?" "He didn't say that evil must always go on." "Donato, are you awake?" "Let's talk a little." "I'm really hungry." "How about you?" "You know what I'm thinking?" "When we are dead the two of us," "Julio from Philadelphia and Stipe, the priest, there won't be anybody in the country who knows how to put up a wall in a professional way." "You remember how much time it took us to put up that skyscraper in New York?" "It was never finished." " How time flies." "It seems like yesterday." "Just a little.." "and then we must die." "And Antò, do you still remember your American?" "A few words." "Work." "Woman." "Money." "Eat." "Love." "Shoes." "Marry." "Strike." "I also knew shirt, but I have forgotten it." "Hey, Antonio!" "Is it true the Americans drive to work?" "Yeah, probably." "But I always went on foot." "Where are you going?" "I need to.." "I must go in a hurry." "Hey!" "Catch me!" "Quiet, they'll hear you!" "How did you get in here?" "You've been here for two days and yet you haven't noticed the other door!" "Did you recognize the whistle?" " I'm no idiot!" "Look what I brought you." "What's in there?" "Are you hungry?" " Yes, I'm hungry." "Come on, eat." "No, I can't." "Nobody'll see you." "If you shouldn't do something, then you shouldn't do it." "Even if nobody sees you." " Oh, come on!" "Where is it?" " In the valley." "They're always having a feast there." "You know what?" "I did the math." "If this fast goes well, we'll book the ticket for you!" "Yeah, but don't forget that this is coming in a few months." "Children, hunger, there can't be anymore of it." "Do you mind if I eat this?" "The more I eat, the bigger he gets." "Angela..," "I always fear that he'll be born with some defect." "I worry about it day and night." "Don't forget the little fingers!" " Now I'm forgetting the little fingers!" "It's not that I don't trust you, but.." "with all these terrors that you feel because of me." "Let him be all he should be." "Two eyes, a nose.., a mouth and a heart and.." "And?" "Don't give me a female or I'll kill you, OK?" "I'll do anything you want, but now you're coming home with me." "The humid air will make you sick." "Come." "If you don't come with me, I won't come anymore." "No, Angela, I must do like the others." "She's beautiful your daughter, Antonio." " Lorenzo is too." "Rest a bit." " No, I won't." "Congratulations!" " You're getting old!" " Congratulations, Antonio!" "You should go out." "Go out and come back." "No, it really wasn't anything special." "Not even a little refreshment." "How do you have the heart to stay here!" "Don't your families mean anything to you?" "Your son returns, you stay here." "You don't even go out to greet him." "Rosa gets married and you act you don't know her." "What ideas did you get in your heads?" "Who put them there?" "When you were a child, I taught you to trust." "I taught to always believe in life, in laws!" "You knew only the children and not the men." "You let go of these men ten years ago." "And the others 30?" "Or 40?" "When these left the country.., family, friends to go to America.." "you weren't with them!" "You weren't with them on the skyscrapers of New York or the mines of Belgium!" "You said that we have no heart." "Maybe." "But what do we have that's different from you?" "Look at us well." "When I and them wake up in the morning and we see the money we have isn't even enough to buy food for the day, and we go to beg for a day's work, a single day's work," "you are not there!" "You don't know us." "Then how can you judge?" "By the law, by only that I judge you!" "For you there is no law!" "No respect." "You think only about money, only about money!" "But there are other things in life." "You taught us to read and to write, we ought to be grateful." "But what use did it serve?" "If you don't have any money, you won't be able to buy even the paper." "And all in my life, I could only allow myself to read four books." "Good Luck!" "Come on, the bus is waiting for us!" "When I went into the military, there was a war." "You're more lucky." "If the money comes, put it aside." "This way, we'll have it when we come back." "We have to leave just as we were beginning to learn something." "If they put you with the engineers, they will always find a wall for you." "True." "Now go." "Listen to me:" "On Sundays, don't waste your time on girls." "Now the city builds with many new methods." "Study them well." "That's how I learned to work with concrete." "Go!" "And grow a mustache!" "If I don't like it, I'll run off." "Goodbye!" "Who destroyed the wall?" "In the evening I left it in place and now it looks like it was bombed." "What do you care?" "It was probably the spirits from the cemetery." "This place is small." "Come outside, so you're more comfortable." "Take this egg, friend." "Dad, come on, you'll die of hunger." "Mom is waiting for you." "Now listen to me well." "That part of the woods, your grandpa stole from the Town it's time to pay it back." "I also made checks on the taxes." "This time I will go all the way!" "If you still want the duty contract, you must pay the Town two years in advance." "And the taxes you'll pay up to the last penny!" "Here!" "Here is everything." "For twenty years you've cheated the Town." "You've taken advantage of government funding." "You've always trafficked with the Town's property." "You did the least you could as mayor." "The job was only a way for you to meet people." "To make you seem more important, to help improve your business." "Now you'll take the responsibility too." "I have a booklet in the bank, forty years of savings." "350 thousand lire in notes." "I put them at your disposal." "And you?" "The road.." "came almost.." "up to the end.." "with a lot of sacrifices." "There were ten months of work." "There were days in jail." "Can you abandon all that you've done, just because the money hasn't arrived yet from the government?" "We need to ask them again and this time we'll get it." "I assure you that they'll give it to us." "But in the meantime, we can't let those people die of hunger." "With all that has happened, not even one reporter came." "But it's better that way." "Better!" "Better because it would've been a shame for us, for the whole country that foreigners were to see that we weren't capable with our own efforts to lift our people up." "Let's lift this shame off our backs but let's do it now." "Because the hungry can't wait." "Everyone give what he can." "This was what I wanted to tell you." "And I told everybody, each and every one of you." "Even if I didn't use names." "Because you know who can give.." "and who cannot." "And who has already given enough." "It's you, eh?" " No, leave me alone." "Now confess!" "You want to.." "hit me?" "I knew you were capable of hitting a woman." "I rebuild your house and you knock it down." "Then you really won't see me." "You want to rebuild the house so.." "you can throw me out of yours." "Me?" "Ah, me?" "No, I'm fine where I am." "Katarina!" "Don't think that now the sacrifices are behind you." "The money is little and you have to make do." "At least until the government realizes its mistake." "The salary will be what it will be." "But the important thing is that it will be." "Now.., go and eat." "Surely, you have a big appetite by now." "Thank you." " Get some rest now." "Good night." " Good night." "Do you need me?" "Good night." " Good night." "Goodnight, Don Remigio." "Matilda, are you sure he's OK?" " Yes, yes, he's just tired." "How many people!" "Let me open this to get out a bit of smoke." "Never have so many people come since you returned from the war with that medal." "How these men smoke!" "It seems like a fog." "All those big and strong hulks!" "They can't give themselves airs with us, can they?" "We remember them when they were all so high." "The first class, then the second, the third, the fifth.." "and then afterwards.." "you lose sight of them." "But just look what they reduced this study to." "This is not the way to come into other people's houses." "Now it's better to close it." "How did you never lose courage?" "I had you and the children." " I helped you so little." "Agnes, now we are old." "Soon they'll ask to get married." "And tomorrow, if they say:" "It's not true at all." "You have to begin the road all over again." "What would you answer?" "All over again with you?" "With all that happened to me:" "the house and the rest." "Why not?" "I've restarted so many times." "You take her a while." "It's as if she were only my daughter." "I struggled for a year to feed a female." "But really, you're obsessed with your females!" "Who got you out of jail?" "Who did the road while you were playing the idiot down there?" "Give her to me!" "Tomorrow, what will I do?" " What do you mean?" "You see, the road is over." "I got used to working every day." "And now what do we do?" "It doesn't matter now we have the visa for America." "America?" "It's not like the draft which expires." "It can wait." "Town of Zagora Road Construction" "It's probably a fancy, but now the valley seems nearer to me." "Even the factories, even the sea." "If you listened to me, the road could be shortened by one kilometer." "The tobacco's here." "When the money is finished, we begin again to make cigarettes with the leaves." "At the new elections, we want you to be mayor, Emil." "But you'll have to let us earn enough money for cigarettes." "Yes, yes!" "With us you won't even have time to sleep." "What's that one doing?" "Bernard, what are you doing?" "Emil, if we make you mayor, think about it!" "There are nine roads that need to be done!" "I counted them all." "One that leads to the fountain." "One that leads to the forest." "One that leads to the pass." "And one that leads to the countryside." "In the meantime, I'll begin that one tomorrow!" "Remember, that a female is not enough." "You can't say that hope exists, and you can't even say it doesn't." "Just like the streets that cut through the earth." "At the beginning there were no roads on the earth:" "they were formed only when many men have traveled the same path." "Lu Hsun" "END Subtitles by sineintegral@KG" | Mid | [
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Captain Earth: Collection 1 [Blu-ray] Blu-ray List Price: $59.98 Price: $32.29 You Save: $27.69(46%) Share Product Notes When Daichi Manatsu sees a mysterious rainbow appearing near the Tanegashima Space Center, he immediately recognizes it as being similar to an apparition that formed when his father was killed in a mysterious accident years earlier. Traveling to Tanegashima, Daichi quickly finds himself involved with the machinations of Globe, a secret agency created to defend mankind from extraterrestrial forces. And while it might seem like a big job for a mere teenager, it turns out that the skills Daichi has honed on video games, combined with a special weapon called the Livlaster, make Daichi ideally suited for operating the Earth Engine Impacter, a giant robot that may be Mankind's best hope against aliens whose goal is to completely drain our world's lifeforce energy. Fortunately, Daichi won't be on his own, as he's quickly joined by a group of equally dedicated young people who all have their own skills and abilities to contribute to the battle. The war for our planet has begun, and the fate of Humanity will rest on a handful of teens as Daichi takes command of the Earth Engine and assumes the mantle of CAPTAIN EARTH! Technical Information When Daichi Manatsu sees a mysterious rainbow appearing near the Tanegashima Space Center, he immediately recognizes it as being similar to an apparition that formed when his father was killed in a mysterious accident years earlier. Traveling to Tanegashima, Daichi quickly finds himself involved with the machinations of Globe, a secret agency created to defend mankind from extraterrestrial forces. And while it might seem like a big job for a mere teenager, it turns out that the skills Daichi has honed on video games, combined with a special weapon called the Livlaster, make Daichi ideally suited for operating the Earth Engine Impacter, a giant robot that may be Mankind's best hope against aliens whose goal is to completely drain our world's lifeforce energy. Fortunately, Daichi won't be on his own, as he's quickly joined by a group of equally dedicated young people who all have their own skills and abilities to contribute to the battle. The war for our planet has begun, and the fate of Humanity will rest on a handful of teens as Daichi takes command of the Earth Engine and assumes the mantle of CAPTAIN EARTH! | Mid | [
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a be p(5). Let m = 4743 + -4578. Calculate the highest common factor of a and m. 15 Suppose -30*j = -25*j - 45. Calculate the greatest common divisor of j and 6. 3 Let r be 6/(-14) + (-13)/((-91)/269). Calculate the greatest common factor of r and 209. 19 Suppose 20 = -4*w, -5*w + 8 = o - w. Let z = o - 17. Let x(q) = 2*q - 21. Let g be x(z). What is the highest common factor of g and 1? 1 Let g = -528 - -812. Let a = g + -199. Calculate the highest common divisor of a and 17. 17 Let t(j) = -j**2 + 10*j - 15. Let g be t(7). Suppose -56 = -g*d + 2*d. Let n(s) = 127*s**2 - 1. Let m be n(1). What is the greatest common factor of m and d? 14 Suppose -5*r = -3549 - 901. Suppose -3*b - 2*v = -r, 5*v = -3*b - 109 + 1002. Let g = b + -205. What is the greatest common divisor of 13 and g? 13 Suppose -y + 2*l + 22 = 0, -5*l - 1 = -6. Calculate the highest common divisor of y and 1080. 24 Let m(b) = b**3 + 13*b**2 - 4*b - 1. Let f be m(-13). What is the greatest common divisor of f and 119? 17 Suppose -20*k - 608 = -28*k. What is the greatest common divisor of k and 19? 19 Let y(q) = q + 21. Let r be y(-17). Suppose 2*z - 22 = -r*a, -5*z - 65 = -0*a - 5*a. Calculate the highest common factor of 1 and a. 1 Let q(m) = m + 20. Let r be q(-13). Suppose -3*l - 2*v + 101 = -2*l, 3*l + 3*v - 288 = 0. Calculate the highest common factor of r and l. 7 Suppose 2 + 4 = 3*l. Suppose 0*i + l*i - 156 = 0. Let o = i - -2. Calculate the highest common factor of o and 20. 20 Suppose -f + 9*f = -8. Let u(z) = 222*z**2 - 3*z - 1. Let t be u(f). Calculate the highest common factor of t and 14. 14 Let z be ((-30)/9)/(3 - 545/180). What is the highest common divisor of z and 300? 60 Suppose -54*c + 29 = -53*c. Calculate the highest common factor of c and 2059. 29 Suppose -2503 = -21*c + 1865. Calculate the highest common factor of 26 and c. 26 Suppose -13 = -3*a + 5*q + 2, 29 = 2*a + 3*q. Let s = a - 7. Calculate the greatest common divisor of s and 21. 3 Let i be (-1)/(-2)*(-1 + 15). Suppose -2*c = -1 - i, -2*q - c = -10. What is the highest common divisor of 3 and q? 3 Let n(i) = i**3 + 5*i**2 - 7*i - 3. Let v be n(-6). Let h(r) = 14*r + 227. Let o be h(-16). Calculate the highest common factor of o and v. 3 Let m be 4*(-1 - -5) + -11 + 7. Let l be -2 - 86/((-1)/1). Calculate the highest common factor of l and m. 12 Let u = 530 - -302. Suppose s - u = -12*s. Let p(h) = 3*h + 4. Let q be p(4). What is the highest common divisor of q and s? 16 Let m be 12/15*30/4. Let c(r) = -r**3 - 2*r**2 - 5*r - 3. Let p be c(-2). Suppose -3*h - 48 = -p*h. Calculate the highest common factor of m and h. 6 Suppose 4*x - 245 = -x. Suppose -3*q - 2*s = -x, -4*s = -q - s + 9. Suppose -w + q = 2*w. Calculate the highest common factor of 35 and w. 5 Suppose u + u = 0. Suppose u = -s - s + 18. Let b = -33 - -69. Calculate the highest common divisor of b and s. 9 Let x = 2 - 1. Let n be x*(1 + (0 - -5)). What is the greatest common factor of n and 3? 3 Suppose -5*o + 14 + 11 = 0. Suppose -2*f = -o - 15. Suppose -47*v + 1825 = -3345. What is the highest common divisor of v and f? 10 Let t be (21/12)/((-14)/(-4368)). What is the highest common divisor of 294 and t? 42 Let w(p) = p**2 + 17*p - 30. Let d be w(-14). Let j = d - -86. Suppose -4*v + 16 = -40. What is the greatest common divisor of v and j? 14 Let z(i) be the second derivative of 0 + 0*i**2 + 1/6*i**4 - 2/3*i**3 + 3*i. Let k be z(-4). Calculate the highest common factor of k and 6. 6 Suppose 386 = -3*j - 3*a - 55, 3*j - 5*a = -433. Let q = j - -157. What is the highest common factor of q and 77? 11 Let g = -693 - -885. Calculate the highest common factor of 320 and g. 64 Let v be (5 - 11)/3 - (1 - 11). Suppose 3*b - 12 = -3*n, -4*b = -4*n - 0*b - v. What is the greatest common factor of 7 and n? 1 Let m(a) = -a**3 - 2*a**2 + 14*a + 33. Let v be m(-5). Calculate the greatest common factor of v and 133. 19 Let h = 24 + 61. Calculate the highest common factor of h and 68. 17 Suppose -2 = -c, 64 = -2*l + 6*l - 2*c. Let b = l - 16. Suppose 3*o - 5 = 2*o. Calculate the highest common divisor of o and b. 1 Let n(c) = -2*c - 1. Let s be n(-1). Let o(m) = 20*m - 4. Let y be o(s). Calculate the greatest common divisor of 24 and y. 8 Suppose -5*f + 11 + 14 = 0. Let u(g) = g**3 - g**2 - 5. Let d be u(f). Let s = 11 + 8. What is the highest common divisor of d and s? 19 Let s be -4*4/(-16)*5 - -50. What is the greatest common factor of s and 33? 11 Suppose 2*b - 10 = 2*q, -5*b + 26 = q - 23. What is the highest common factor of b and 27? 9 Suppose -5*p + 12 = f - 40, 4*p + 4*f - 32 = 0. Calculate the greatest common divisor of p and 1. 1 Let s be (-2)/10 - (-23782)/110. What is the greatest common divisor of 24 and s? 24 Let k(d) = 4*d**2 - 4*d - 3. Let r be k(4). Let h be (1/2)/(-5*(-1)/90). What is the highest common divisor of h and r? 9 Let h be (-212)/(-9 + 215/25). Calculate the highest common divisor of 10 and h. 10 Let k be 161/35 - 6/10. Let a be 125 + (-3)/(-12)*k. Calculate the greatest common divisor of 14 and a. 14 Suppose -5*k = -2*v + 243, 0 = -412*k + 408*k - 12. Calculate the highest common divisor of v and 102. 6 Let r be (3/(-7) - 104256/168)/(-1). What is the greatest common factor of r and 108? 27 Let g(t) = t**3 - 13*t**2 - 2*t + 24. Let r be g(13). Let d(u) = u**2 - 4*u - 5. Let z be d(r). What is the highest common divisor of z and 7? 7 Suppose -74*f - 20526 = -64038. Suppose t + 0 - 2 = 0. Suppose n = -t*n + f. Calculate the highest common factor of n and 28. 28 Suppose k - 5*o - 16 = 0, -2*k - 2*k = -4*o - 96. What is the highest common divisor of 221 and k? 13 Suppose 4*n + 19*n - 10787 = 0. Calculate the highest common divisor of 7 and n. 7 Suppose 7*x + 59 - 17 = 0. Let a be (14 + x/(-2))*-5. Let h = a + 147. What is the highest common factor of h and 155? 31 Let l = 126 + -77. Let f be ((-296)/(-7) - 0) + (-14)/l. Calculate the highest common divisor of f and 28. 14 Let s = 216 - 156. Calculate the highest common divisor of 30 and s. 30 Let g = 0 + -5. Let f(c) = -c - 3. Let o be f(g). Calculate the highest common divisor of o and 3. 1 Let f(o) = -o**2 + 18*o + 40. Let a be f(10). Calculate the greatest common divisor of a and 15. 15 Let u(d) = -31 - 10*d - 3*d**3 - 11*d**2 + 23 + d**3. Let a be u(-8). What is the highest common divisor of 49 and a? 49 Let a be ((3060/(-16))/17)/((-2)/8). What is the greatest common factor of a and 180? 45 Suppose -15 = -3*k - 6. Suppose 2*s - 5 = -d, -d + k = -0*d. Calculate the highest common divisor of 11 and s. 1 Let t(l) = -10*l + 54. Let j be t(4). What is the highest common divisor of j and 574? 14 Suppose -t - g = 2*t - 221, -5*t - 5*g = -385. Let j = t + 5. What is the highest common divisor of 7 and j? 7 Let t = 40 - 3. Calculate the highest common divisor of t and 111. 37 Let h = 143 - 73. Let p be (4/12)/((-1)/(-9)). Suppose 4*g + 58 = 3*q, 4*g - 3 = -p*q + 23. Calculate the highest common divisor of h and q. 14 Suppose 0 = 3*s - 2*s - 58. Suppose -93 - 1067 = -2*p. Suppose -23*f - p = -27*f. What is the highest common factor of f and s? 29 Suppose 0 = -2*z + 17 + 103. Calculate the greatest common divisor of 144 and z. 12 Let p(s) = 3*s**2 - 24*s + 5. Let h be p(9). Calculate the highest common divisor of h and 64. 32 Let p(n) = n**2 + 24*n - 177. Let y be p(-31). Calculate the highest common divisor of 1 and y. 1 Let x be 2 + (5/(20/12))/1. Suppose 0 = q - x*v - 47, -3*v - 45 = -q + v. What is the greatest common divisor of q and 333? 37 Let h = -11 + 13. Let m be (-711)/h*(-8)/6. Suppose 0 = -2*z - 3*i + 299, 0*i - m = -3*z + 4*i. What is the greatest common divisor of 22 and z? 22 Let l = 401 - 169. Let q = 352 - l. Let j(d) = 11*d**3 + 2*d**2 - 2*d + 1. Let k be j(1). Calculate the greatest common factor of q and k. 12 Let y(w) = 13*w + 2 + 90*w + 11 + 2. Let z be y(3). Calculate the highest common divisor of z and 36. 36 Let l = 1783 - 1678. Calculate the greatest common divisor of l and 455. 35 Suppose -19 = i - 5*b + 1, -5*b = -5*i. Let r = -5 - -10. What is the greatest common factor of i and r? 5 Let d be 162 + 1*6/12*-2. What is the highest common factor of 345 and d? 23 Suppose -9*q = 38*q - 2256. What is the greatest common divisor of q and 512? 16 Suppose 79 | Low | [
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Q: Is it possible to execute vb.net code using vs2010 without running the project? This may be a strange question and have no answer but I thought I would post it to see how you would go about doing it. I have a line of code: Grade = Math.Round((Math.Abs(CorrectAnswers) / TotalQuestions) * 100) Basically that line just figures out the grade no major code work there, what I want to do is execute that specific line with different variables without running the whole application and navigating to the point in the application which for this segment would be completing a 150 question exam, or coding some #temp page and running it from there. I am trying to track a bug in the code that happens very rarely (you know when the planets in the universe are out of cosmic alignment) and I think my issue lies with this subset and I am trying to find a better/easier way of testing it. A: If you add a Class Diagram item to the project and from Solution Explorer you drag the class file which contains the method into it, you can invoke static methods (right click on the Class element or use Class Diagram Menu). It will ask you the values for the arguments. And really you do can use Immediate window (Ctrl+G or Debug->Windows menu) Open it and type: CorrectAnswers=25.5 TotalQuestions=30 ?Math.Round((Math.Abs(CorrectAnswers) / TotalQuestions) * 100) And you'll get: 85.0 {Double} Double: 85.0 Tip: type >cls to clear the immediate window contents. I don't understand how Bill says he misses it from VB6. We have it too at VisualStudio and fully functional :) Regards. ps:I translate from the spanish 2008 version so you could have other menu options, hotkeys, etc. | High | [
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13 Cal.App.2d 134 (1936) HELEN P. THOMPSON, Appellant, v. BOARD OF SUPERVISORS OF THE COUNTY OF FRESNO et al., Respondents. Civ. No. 1732. California Court of Appeals. Fourth Appellate District. April 7, 1936. Everts, Ewing, Wild & Everts, A. W. Carlson, C. L. Clark and Richard H. Reeve for Appellant. Arthur C. Shepard for Respondents. Barnard, P. J. In this proceeding petitioner sought to cancel certain taxes and to remove the lien thereof from certain real property in Fresno County. The petitioner is the widow of Claude M. Thompson, who died in April, 1930. Prior thereto he had been a partner in a business conducted under the name of Thompson Brothers, and in another business conducted under the name of Fresno Builders' Supply Company. Thereafter, his brother E. O. Thompson continued the business of these two partnerships as surviving partner. The petitioner acquired the interest of her husband in these two partnerships but the same was not distributed to her until some time after July 25, 1931. On the first Monday in March, 1931, the real property on which the business of these two partnerships was conducted stood of record in the name of the petitioner and of E. O. Thompson, each of them owning an undivided one-half interest therein. On July 25, 1931, E. O. Thompson conveyed his *136 half interest in this real property to the petitioner. On the first Monday in March, 1931, the assessor of Fresno County assessed certain personal property belonging to these two partnerships with the real property above referred to and thereby charged this real property with the payment of the tax on this personal property. The petitioner brought this proceeding seeking a writ of mandate to compel the respondents to cancel the assessment of this personal property thus levied. In her petition she alleged that on the first Monday in March, 1931, she and E. O. Thompson each owned an undivided one-half interest in this real property; that thereafter E. O. Thompson conveyed to her his one-half interest therein and that she is now the sole owner thereof; that on or about the first Monday in March, 1931, the county assessor assessed a tax upon this personal property; that on that date neither the petitioner nor E. O. Thompson owned the personal property so assessed, nor was it on said date or at any time since the property of the said E. O. Thompson or of the petitioner; that on October 13, 1934, the petitioner made a written demand upon the respondent Board of Supervisors for a cancellation of said tax upon said personal property upon the ground that said assessment was illegally made, in that the personal property had been assessed to the petitioner as the owner thereof whereas the petitioner was not the owner thereof at the date of the assessment; and that the respondent board had refused to cancel the assessment. After a trial the court entered a judgment directing the issue of the writ as prayed for as to the undivided one-half interest in said real property owned by the petitioner on the first Monday in March, 1931, but denying any relief as to the one-half interest in said real property owned by E. O. Thompson on said date and thereafter conveyed to the petitioner. From this judgment the petitioner has taken this appeal. We are here concerned with that portion of the judgment denying relief as to that part of the real property which was owned by E. O. Thompson and later conveyed by him to the appellant. If the tax on this personal property became a lien on his interest in this real property the appellant acquired title subject to that lien. (Reeve v. Kennedy, 43 Cal. 643.) *137 [1] It is first contended that there was no valid assessment of this personal property for the reason that it was assessed to persons other than the owner thereof. This is based upon the argument that the personal property in question was owned by the partnerships, that these partnerships were separate entities and that while E. O. Thompson owned an interest in these partnerships and the appellant had an interest in the estate of her husband which later ripened into an interest in the partnerships, neither of them owned the personal property which was assessed and therefore the assessment, not having been made to the partnership as owners of the property, was invalid and void. In so far as the validity of this assessment in itself is concerned, we think the matter is settled by the reasoning and principles set forth in RCA Photophone, Inc., v. Huffman, 5 Cal.App.2d 401 [42 PaCal.2d 1059], and by the provisions of section 3628 of the Political Code. E. O. Thompson, as surviving partner, was in possession of the personal property in question and an assessment to him was a sufficient compliance with the requirement of the code that it be assessed to the owner or to the one in whose possession or control it was. [2] It is next contended that the assessment, if valid, could not become a lien upon property owned by E. O. Thompson because he was not the owner of the personal property. Section 3717 of the Political Code provides that such a tax on personal property is a lien upon the real property of the owner thereof. We think the word "owner" in section 3717 of the Political Code was intended in the same sense as the word "owned" in section 3821 of that code, the latter section having been interpreted and applied in the case of RCA Photophone, Inc., v. Huffman, supra. As we said in that case: "While it is true that statutes under which taxes are levied for public purposes are to be strictly construed in favor of the individual and against the taxing power it is equally true that language must not be given an unnatural construction in order to defeat the tax legislation nor the plain intent of legislation disregarded." While property may be said, in a technical sense, to belong to a partnership rather than to the individuals composing the same, in a practical and very real sense such property is owned by the partners and at least for the purpose of taxation may be so considered. If a person is sufficiently an "owner" to permit the assessment to *138 be made to him, and to become liable for its payment, he is sufficiently an "owner" to permit the tax to become a lien on his real property. This conforms to common experience and if it were not true, the tax on partnership property could never be assessed with the real property of the real owners thereof but must always be collected at the time, or the personal property seized and sold. In our opinion this was not the intention of these statutes and it is not necessary to give them such an unnatural and technical construction. If E. O. Thompson, as the real owner of a half interest in this personal property and as the one in possession and control of all of it, authorized it to be assessed with his real estate, the same must be held to constitute a valid lien. He was the owner of the property, within the meaning of these statutes, and personally liable for the payment of the tax, and there is nothing in the situation to prevent the tax from becoming a lien on his real property, at his request and with his consent. [3] The appellant contends that the evidence is not sufficient to show that E. O. Thompson authorized the placing of this assessment against his half interest in the real property. The assessment record was introduced in evidence showing a direction to assess this personal property with this real property, the statement being signed by one Jeffords as manager for each partnership. There is evidence that these and all other affairs of these partnerships had been long handled as a family affair, that the assessment of this personal property had been handled in this manner for several years before the year in question, that Jeffords was trying to straighten out the affairs for the family, that E. O. Thompson had in past years directed the assessor to assess the property in this manner, and Jeffords testified that E. O. Thompson had authorized him to do so in this instance. The appellant testified that she and E. O. Thompson were the guiding spirits in the partnerships, that the tax statements were gotten out in the office, and that she could not recall whether or not E. O. Thompson had promised to pay the taxes. [4] It is argued that Jeffords could have had no authority to turn in this tax statement unless the same was in writing, under the statute of frauds, as otherwise the effect would be to make E. O. Thompson undertake to answer for the debt of another. As a surviving partner E. O. Thompson was liable for all debts of the partnership and if he undertook to pay or secure such *139 indebtedness as this tax he was not agreeing to answer for the default of another within the meaning of the statute of frauds. While we think the evidence, with the reasonable inferences therefrom, is sufficient to sustain the finding that E. O. Thompson authorized the making of this assessment in this manner, this finding was not necessary to the judgment. [5] A statement was put in and the tax was assessed against this real property. It was the duty of E. O. Thompson to make such a statement under section 3629 of the Political Code. It must be presumed that he did his duty and there is no evidence of any other statement having been made. It must also be presumed that the assessor performed his duty in making the assessment. Moreover, this proceeding was brought by the petitioner and the burden rested upon her to show that the assessment had been illegally made against this property. There is absolutely no evidence to show that the statement was made without the authority of E. O. Thompson and the petitioner has failed to produce any evidence to show that she was entitled to relief. It is significant, in this connection, that E. O. Thompson was not called by the appellant as a witness. It may be added that the record sufficiently shows that both E. O. Thompson and the petitioner are estopped from attacking this assessment after the lapse of several years. In so far as is shown by the record, all of the equities are on the side of the respondents. The judgment appealed from is affirmed. Marks, J., and Jennings, J., concurred. | Low | [
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The F233;d233;ration Internationale de Football Association (FIFA ˈ f iː f ə FEEF-ə; French for quot;International Federation of Association Footballquot;) is an association which describes luisino poker star as an international governing body wtar association football, futsal, and beach soccer. Luisino poker star MediaLatest updates Update list Celebrities A-Z Top Adders Contact Info Links Thousands of gambling or not pictures and movies. | Low | [
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Background ========== Autoimmune hepatitis (AIH) is a progressive inflammatory fribrosing disease of the liver of unknown etiology, which in its normal progress leads to cirrhosis. It is characterized by the increase in aminotranferases and hypergammaglobulinemia, and the presence of non-organ and specific liver autoantibodies in serum, which allow for its classification. Two subtypes are differentiated: Type I AIH with anti-smooth muscle antibodies (SMA) and/or antinuclear antibodies (ANA); and Type II AIH with antimichondrial antibodies (LKM). AIH can be associated with other autoimmune illnesses such as thyroiditis, Type I diabetes, thrombocytopenia, hemolytic anaemia and ulcerative colitis. Likewise, the association to connective tissue diseases (CTD) has been communicated, such as Systemic Lupus Erythematosus, Sjögren's Syndrome, Undifferentiated Connective Tissue Disease, Mixed Connective Tissue Disease, Localized Sclerodermia and Juvenile Idiopathic Arthritis. Aim === We aim to research defined or probable clinical and laboratory manifestations of CTD in patients with AIH diagnosis in pediatric age. Methods ======= 20 records of patients with AIH diagnosis under care in the Hepatology Unit and Rheumatology Unit were analyzed retrospectively since 1995 until May 2008. Results ======= In the group of 20 patients, 6 were male (30%) and 14 were female (70%). Their average AIH diagnosis age was 9.6 yrs (Min 1.4 yrs-Max 15.2 yrs). Type I AIH diagnosis occurred in 18/20 patients (90%), 5 males (27.8%) and 13 females (72.2%), their average diagnosis age being 9.8 yrs (Min 1.4 yrs-Max 15.2 yrs), and Type II AIH diagnosis occurred in 2/20 patients (10%), 1 male and 1 female. Their average AIH diagnosis age was 7.5 yrs (Min 4.2 yrs-Max 10.9 yrs). Average follow-up period of the patients until the end of the study was 41.4 months in average. 8/20 patients with defined AIH (40%) showed some manifestations of CTD in their progress; 6/18 patients with Type I AIH (33.3%), 2 males and 6 females, and 2/2 patients with Type II AIH (100%). Most common manifestations were: arthralgia/arthritis, vasculitis, AHA with positive Coombs' Test results, oral ulcers, hypocomplementemia, leukopenia/lymphopenia and positive ANA results. CTD defined diagnosis were: SLE, vasculitis, Sjörgren's Syndrome and Overlap Syndrome. In the remaining 4 patients diagnosis was probable. In one patient manifestations of CTD were simultaneous with AIH diagnosis. In 3/8 patients manifestations were before (25 months average) and in 4/8 were afterwards (29 months average). Conclusions =========== In 8 out of 20 patients AIH was associated with defined or probable CTD. Three of the 8 patients developed AIH after CTD diagnosis. This association should be investigated in all patients with AIH and CTD diagnosis. | High | [
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Spontaneous and induced chromosomal damage and mutations in Bloom Syndrome mice. Bloom Syndrome (BS) is characterized by both cancer and genomic instability, including chromosomal aberrations, sister chromosome exchanges, and mutations. Since BS heterozygotes are much more frequent than homozygotes, the issue of the sensitivity of heterozygotes to cancer is an important one. This and many other questions concerning the effects of BLM (the gene responsible for the BS) are more easily studied in mice than in humans. To gain insight into genomic instability associated with loss of function of BLM, which codes for a DNA helicase, we compared frequencies of micronuclei, somatic mutations, and loss of heterozygosity (LOH) in Blmtm3Brd homozygous, heterozygous, and wild-type mice carrying a cII transgenic reporter gene. It should be noted that the Blmtm3Brd is inserted into the endogenous locus with a partial duplication of the gene, so some function of the locus may be retained. The cII reporter gene was introduced from the Big Blue mouse by crossing them with Blmtm3Brd mice. All measurements were made on F2 mice from this cross. The reticulocytes of Blmtm3Brd homozygous mice had more micronuclei than heterozygous or wild-type mice (4.5, 2.7, and 2.5 per thousand, respectively; P < 0.01) but heterozygotes did not differ significantly from wild-type. Unlike spontaneous chromosome damage, spontaneous mutant frequencies did not differ significantly among homozygous, heterozygous, and wild-type mice (3.2 x 10(-5), 3.1 x 10(-5), and 3.1 x 10(-5), respectively; P > 0.05). Mutation measurements were also made on mice that had been treated with ethyl-nitrosourea (ENU) because Bloom Syndrome cells are sensitive to ethylating agents. The ENU-induced mutation frequency in Blmtm3Brd homozygous, heterozygous, and wild mice were 54 x 10(-5), 35 x 10(-5), and 25 x 10(-5) mutants/plaques, respectively. ENU induced more mutations in Blmtm3Brd homozygous mice than in wild-type mice (P < 0.01), but not significantly more in heterozygous mice (P = 0.06). Spontaneous LOH did not differ significantly among the genotypes, but ENU treatment induced much more LOH in Blmtm3Brd homozygous mice, as measured by means of the Dlb-1 test of Vomiero-Highton and Heddle. Hence, these Blmtm3Brd mice resemble Bloom Syndrome except that they have normal frequencies of spontaneous mutation. The fact that these mice have elevated rates of both cancer and chromosomal aberrations (as shown by more micronuclei and LOH) but normal rates of spontaneous mutation, shows the greater importance of chromosomal events than mutations in the origin of their cancers. | Mid | [
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Q: Act upon document upload in Sharepoint I've been requested to help a friend where he wants all uploaded documents to be converted to PDF and save the URL into a small database for later use. Can anyone explain me what should I look or what method I need to override to create such workflow? This needs to be available to all documents (even images). Thank you. A: Have a look at this post, it does exactly what you need although you may need to pull some tricks to write the URL into an external database. Writing it to a SharePoint list is easy. Ping me if you need help. | High | [
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Q: permanently replace values in a list using Python list1 = [1,2,3,4,5,6,7,8,9] def replace(): input_list = input("Enter three numbers separated by commas: ") list2 = input_list.split(',') list2 = [int(x.strip())for x in list2] del list1[-3:] list1.insert(0,list2) print(list1) for input 12,13,14 this gives as a result [[12,13,14],1,2,3,4,5,6] Firstly I would like to have a 'flat' list as the result and can't seem to get this right [12,13,14,1,2,3,4,5,6]. I can get the last value entered as part of the list by removing the square brackets from the list2=[int(x.strip()) for...] statement, gives [14,1,2,3,4,5,6]. My second wish is that I can change the initial list permanently ie [12,13,14,1,2,3,5,6] becomes list1 that is called in the first place. Do I need to save this as a csv file and write to it? I am very new to this, so please forgive me if this is a very simple or stupid batch of questions. A: I believe this is what you want: In [11]: list1 = [1, 2, 3, 4, 5, 6] In [12]: list2 = [12, 13, 14] In [13]: list1[0:0] = list2 In [14]: list1 Out[14]: [12, 13, 14, 1, 2, 3, 4, 5, 6] The slice operation changes list1 in-place, so the variable isn't simply pointing at a new list. I think that's what you meant by "permanently"? | Mid | [
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Initial Coin Offerings (ICOs) and crowdsales have become the new way of fundraising in the startup ecosystem. If the company or the product has got remotely anything to do with blockchain or fintech, then the chances of success are much higher. Tezos, a blockchain self-governance platform has proven it by breaking records to become the highest grossing ICO of all times. The recently concluded Tezos crowdsale has raised over $230 million within a span of 13 days. The ICO which went live on July 1, 2017, attracted 65,645 BTC and 361,112 ETH, surpassing all the earlier records to become the most successful ICO ever. The total funds collected by Tezos is at least $80 million more than Bancor, which held the previous record by raising a total of about $150 million. The creators of the platform call Tezos a “self-amending” cryptoledger, which entirely transfers the power to decide network-wide protocol level changes to the stakeholders. The model adopted by Tezos is expected to prevent a repeat of the issues currently being faced by Bitcoin Network and the earlier predicament that forced Ethereum to introduce a hard fork. The platform is conceptualized by Dynamic Ledger Solutions Inc, a company founded by Arthur and Kathleen Breitman. Arthur’s education includes math, physics, and computer science. He has been intimately involved in the financial industry as well, following his stints in Goldman Sachs and Morgan Stanley. Similarly, Kathleen has been associated with the Wall Street Journal, Bridgewater Associates, Accenture, and R3. Apart from the founders, the Tezos platform is backed by a dynamic development team with lots of experience in computer science related subjects. In addition, the advisory board includes heavyweights like Zooko Wilcox from ZCash, Emin Gun Sirer, and Andrew Miller. The success of the ICO is dependent not only on the project and its capabilities to solve real-world problems, but also the names associated with the projects. In Tezos’ case, the project has the right combination of both, which has played a pivotal role in the successful multimillion dollar crowdsale. Ref: Futurism | Tezos Whitepaper | Image: NewsBTC | High | [
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Introduction {#Sec1} ============ Curcumin (diferuloylmethane) from turmeric plant *Curcuma longa* and its derivatives known as curcuminoids have been recognized to be effective in experimental studies for a very large number of diseases with an equally large number of diverse molecular targets^[@CR1],\ [@CR2]^. More specifically, curcumin has been tested as an anti-inflammatory agent for treatment of cancers and other diseases^[@CR3],\ [@CR4]^. Based on its immunomodulatory properties, curcumin has also been suggested as an adjunct drug for the treatment of many infectious diseases^[@CR5]^. In spite of extensive clinical trials using curcumin, and its classification as a generally recognized as safe (GRAS) molecule, it is still not an approved drug even for a single ailment^[@CR6]^. The main reasons include poor water solubility, low bioavailability, rapid metabolism and clearance from body^[@CR6],\ [@CR7]^. It has been suggested that nanocurcumin represents a promising therapeutic advancement over native curcumin^[@CR8]^. It is in this context that we want to report our results obtained with curcumin nanoparticles prepared using poly(lactide-co-glycolide) (PLGA) in comparison with native curcumin to treat experimental cerebral malaria (ECM). Human cerebral malaria (HCM) is a serious complication with high mortality (15--25%) despite the existing standard therapy using artemisinin derivatives. Hence, there is a need for adjunct therapy^[@CR9]^. Inflammation in brain, blood-brain barrier (BBB) breakdown and sequestration of parasitized-RBCs (pRBCs) are the major factors contributing to high mortality in HCM. Despite some differences, ECM in *Plasmodium berghei*-infected mice has been shown to share many features of HCM and is considered very useful to dissect the mechanisms involved and screen drug molecules^[@CR10]--[@CR12]^. Curcumin, when given orally by gavage during 0--5 days post-infection, has been shown to delay death of mice (C57BL/6) in the ECM model, reversing the symptoms of cerebral malaria^[@CR13]^. We have recently shown that native curcumin alone is effective in counteracting the neurological symptoms and inflammation parameters of ECM with a significant delay in the mortality of mice, which eventually died due to anemia caused by parasite build-up in blood^[@CR14]^. The objective of the present study was to formulate curcumin in low molecular weight PLGA-based nanoparticles (PLGA-curcumin) and evaluate its potential in ECM. PLGA polymers have been extensively used for drug and vaccine delivery^[@CR15],\ [@CR16]^. PLGA- and PLA-based polymers provide interesting features for the sustained delivery of curcumin while protecting its degradation and improving its bioavailability^[@CR17]--[@CR19]^. In a fresh set of experiments carried out in parallel, we compared the efficacies of orally administered native curcumin and PLGA-curcumin. It was observed that PLGA-curcumin was as effective as native curcumin at a 15-fold lower concentration in counteracting the neurological symptoms and inflammation parameters, and in preventing the breakdown of BBB. It was more effective than native curcumin in preventing the sequestration of lymphocytes and pRBCs in brain. PLGA-curcumin, even at a lower curcumin concentration, led to higher concentrations of curcumin in the brain than native curcumin. The results indicated that PLGA-curcumin nanoparticles have the potential to be used as adjunct therapy for treating HCM. Results {#Sec2} ======= Preparation and characterization of PLGA-curcumin {#Sec3} ------------------------------------------------- PLGA nanoparticles entrapping curcumin were prepared using single emulsion solvent evaporation method. Use of acetone and dichloromethane for solubilization of curcumin and PLGA resulted in stable emulsion formation leading to formulation of spherical nanoparticles. The size and zeta potential of curcumin nanoparticles were 495 ± 14.4 nm and −13.8 ± 1.8 Mv, respectively, as measured by Nano zetasizer. Curcumin nanoparticles were found to be spherical and non-aggregated as analyzed by transmission electron microscopy. Size of the PLGA nanoparticles obtained by TEM was in accordance with the results obtained by zetasizer (Fig. [S1a](#MOESM1){ref-type="media"}). PLGA-curcumin nanoparticles showed narrow size distribution and polydispersity index (PDI = 0.24). *In vitro* release of curcumin form PLGA nanoparticles showed characteristic burst release followed by sustained release for 12 days (Fig. [S1b](#MOESM1){ref-type="media"}). Around 15--20% of the total entrapped curcumin was released within six hours. Continuous release of curcumin was observed from the particles and around 65% was released in seven days. This *in vitro* release profile showed that low molecular weight PLGA (with inherent viscosity of 0.2 dl/gm) is suitable for sustained release of entrapped curcumin. Curcumin load and entrapment efficiency in PLGA nanoparticles were 70 μg/mg and 37.91%, respectively (Table [S1](#MOESM1){ref-type="media"}). Effect on parasite growth {#Sec4} ------------------------- The ECM studies were carried out in C57BL/6 mice infected with *P. berghei* ANKA strain. Around 80--90% of infected mice showed typical neurological symptoms between 7 to 10 days, eventually resulting in coma and death. Native curcumin/PLGA-curcumin was fed orally after three days post infection (d.p.i) and 5 mg of each was given in three oral doses at 24 h interval. The treatments were started before the onset of neurological symptoms. Since PLGA-curcumin contained 70 μg curcumin/mg, it provided only 350 μg of curcumin/dose. The results presented in Fig. [1a](#Fig1){ref-type="fig"} indicate that the infected mice without treatment died around 10--12 d.p.i. In accordance with results obtained in earlier studies^[@CR20],\ [@CR21]^, these mice showed typical neurological symptoms and died when the parasitemia was around 15% (Fig. [1b](#Fig1){ref-type="fig"}). At the concentrations provided, both the preparations could completely eliminate the neurological symptoms and the mice died of anemia between 22 to 25 d.p.i. (Fig. [1a](#Fig1){ref-type="fig"}), when the parasitemia was around 40% (Fig. [1b](#Fig1){ref-type="fig"}). Since PLGA-curcumin provided only 350 μg of curcumin/dose, it was of interest to compare the efficacy of native curcumin at 350 μg/dose with PLGA-curcumin. The results presented in Fig. [1c](#Fig1){ref-type="fig"} indicate that with three oral doses of native curcumin at 350 μg/dose, 75% of the mice died between 16--18 days, whereas with PLGA-curcumin, all the mice died between 22--25 days, similar to the results obtained with three oral doses of 5 mg native curcumin/dose. Some of them in the native curcumin group (350 μg) died by manifesting neurological symptoms with a parasitemia around 18--20% (Fig. [1d](#Fig1){ref-type="fig"}), whereas none of the mice given three doses of PLGA-curcumin or native curcumin (5 mg) showed neurological symptoms. In the rest of the experiments, the results obtained with three oral doses of 5 mg of native curcumin were compared with three oral doses of 5 mg PLGA-curcumin, providing 350 μg of native curcumin/dose. Data from PLGA alone controls were very similar to those obtained from infected animals without drug treatment.Figure 1Effect of native curcumin and PLGA-curcumin on survival of *P. berghei*-infected mice and parasitemia in blood. (**a**,**c**) Percentage mortality of *P. berghei*-infected mice. (**b**,**d**) Percentage parasitemia of *P. berghei*-infected mice. Data are presented as mean + S.D. \*P \< 0.05; \*\*P \< 0.001; \*\*\*P \< 0.0001; ns, not significant. The bar represents the partners compared. Effect on BBB breakdown and pRBC sequestration in brain {#Sec5} ------------------------------------------------------- A crucial event in HCM and ECM is the breakdown of the BBB associated with the sequestration of pRBCs and lymphocytes in the brain^[@CR12],\ [@CR22],\ [@CR23]^. We have shown earlier that native curcumin can counteract this derangement^[@CR14]^, measured in terms of Evans Blue staining of the brain. The results presented in Fig. [2a](#Fig2){ref-type="fig"} indicate that PLGA-curcumin was at least as effective as native curcumin in preventing the breakdown of BBB. Next, pRBC sequestration in the brain was measured using *P. berghei* ANKA strain expressing luciferase. The mice were injected with luciferin and the bioluminescence of the brain was measured *ex vivo*. The results presented in Fig. [2b](#Fig2){ref-type="fig"} indicate that PLGA-curcumin was superior to native curcumin in inhibiting pRBC sequestration. While native curcumin treatment showed a low level of pRBC sequestration, brain from PLGA-curcumin treated mice could not be distinguished from uninfected mice. PLGA particles alone used as control did not prevent pRBC sequestration in the brain. Whole body imaging carried out on day 5, 7 and 10 post infection and the quantification of bioluminescence indicated that PLGA-curcumin was more effective than native curcumin in preventing pRBC sequestration (Fig. [S2](#MOESM1){ref-type="media"}). Parasite concentration in the brain was also assessed by performing quantitative PCR for parasite *18S rRNA*. This also showed greater inhibition with PLGA-curcumin than that obtained with native curcumin. (Fig. [2c](#Fig2){ref-type="fig"}).Figure 2Comparison of the effects of native curcumin and PLGA-curcumin on BBB breakdown and pRBC sequestration in *P. berghei*-infected mice. (**a**) Evans Blue staining of brain in *P. berghei*-infected mice. (**b**) *Ex vivo* bioluminescence imaging of brain in *P. berghei*-infected mice. (**c**) Quantitative PCR for parasite *18S rRNA* in the brain samples of *P. berghei*-infected mice. P value comparison is between infected and treated animals. Effect on inflammatory parameters {#Sec6} --------------------------------- ECM is characterized by a striking increase in inflammatory cytokines and chemokines associated with the breakdown of BBB and lymphocyte sequestration^[@CR24]--[@CR26]^. The results presented in Fig. [3a](#Fig3){ref-type="fig"} indicate that both native curcumin and PLGA-curcumin were effective in counteracting the increase in brain mRNAs for chemokines (CXCL9 and CXCL10), chemokine receptor (CXCR3), inflammatory cytokines (IFNγ and TNFα), inflammatory marker (Granzyme B), CD8^+^ T cell marker (CD8β) and adhesion molecule (ICAM-1). The inflammatory (IFNγ and TNFα) and anti-inflammatory cytokine (IL-10) and chemokine (CXCL10) levels were measured in serum as well. The results presented in Fig. [3b](#Fig3){ref-type="fig"} indicate that IFNγ, TNFα, CXCL10 and IL-10 levels increased in the infected serum. Native curcumin and PLGA-curcumin inhibited the striking increase in the serum levels of the inflammatory cytokines and the chemokine. Interestingly, both native curcumin and PLGA-curcumin further enhanced the levels of the anti-inflammatory cytokine (IL-10) in serum. The difference between native curcumin and PLGA-curcumin in terms of efficacy was clearly seen with single dose data, providing 350 μg curcumin in either case. The results indicate that the increase in IFNγ was inhibited by 25% and 75% with native curcumin and PLGA-curcumin treatments, respectively. There was a marginal further increase in IL-10 levels with native curcumin and a 100% increase with PLGA-curcumin (Fig. [3c](#Fig3){ref-type="fig"}).Figure 3Comparison of the effects of native and PLGA-curcumin on cytokine and chemokine levels. (**a**) Relative mRNA expression in the brain samples of *P. berghei*-infected mice. (**b**,**c**) Inflammatory and anti-inflammatory cytokine and chemokine levels in the serum samples of *P. berghei*-infected mice. Comparison is between infected and treated animals. Bar represents the partners compared. Effect on NF-kB phosphorylation {#Sec7} ------------------------------- NF-κB activation is an upstream event in enhancing the transcription of inflammatory markers including cytokines^[@CR27]^. Since p65 phosphorylation is a key step in the activation process, the levels of phospho-p65 were measured in the brain lysates. Both native curcumin and PLGA-curcumin treatments led to a decrease in the levels of phospho-P65. A similar pattern was also observed in spleen lysates (Fig. [4](#Fig4){ref-type="fig"}).Figure 4Comparison of the effects of native curcumin and PLGA-curcumin given as per the standard dose schedule on phosphorylation of NF-κB. The images of whole blots are given in Figure [S3](#MOESM1){ref-type="media"}. Effect on sequestration of CD8^+^ T cells in the brain using FACS analysis {#Sec8} -------------------------------------------------------------------------- FACS analysis of lymphocyte population in the brain was carried out for CD3^+^/CD8^+^ (double positive) and CD3^+^/CD8^+^/CXCR3^+^ cells (triple positive). CXCR3 and its ligands are reported to be essential for precipitating ECM and CXCR3-deficient lymphocytes are 7-fold less efficient than wild type cells for migration into the infected brain^[@CR25]^. The results presented in Fig. [5a and b](#Fig5){ref-type="fig"} indicate that native curcumin and PLGA-curcumin inhibited sequestration of the CD8^+^ T cells. Native curcumin and PLGA-curcumin treatments inhibited double positive cells by 50% and 60%, respectively and triple positive cells by 40% and 60%, respectively.Figure 5Comparison of the effects of native curcumin and PLGA-curcumin given as per the standard dose schedule on CD8^+^ T cell sequestration in the brain of *P. berghei*-infected mice. (**a**,**b**) FACS analysis of lymphocyte population in the brain samples of *P. berghei*-infected mice for CD3^+^/CD8^+^ (double positive) and CD3^+^/CD8^+^/CXCR3^+^ (triple positive) cells. Bar represents comparison between infected and curcumin/PLGA-curcumin treated animals. Bioavailability of curcumin {#Sec9} --------------------------- A single oral dose of 5 mg of native curcumin or PLGA-curcumin (providing 350 μg of curcumin) was given to mice and the levels of free curcumin and the glucuronide derivative were measured in plasma and brain by LC/MS analysis (Fig. [6](#Fig6){ref-type="fig"}). With curcumin treatment, the levels of free curcumin were in the range of 2--5 ng/ml of plasma or g of brain between 45 min and 8 h. It was below the limit of detection after 12 h. The glucuronide concentration ranged between 170 to 370 ng/ml in plasma between 45 min and 8 h, indicating rapid metabolism of curcumin. Interesting results were obtained with PLGA-curcumin treatment. 1--2 ng of curcumin/ml was detected in plasma up to 2 h and undetectable after this period. In the brain, the same pattern was seen up to 2 h, but the concentration increased to 12--14 ng/g after 4 h. The concentration was still around 5 ng/g after 12 h. The glucuronide concentration was around 10 to 40 ng/ml in the plasma and this correlated with the fact that PLGA-curcumin provided only 350 μg of curcumin. In general, plasma and brain showed a higher concentration of curcumin in infected mice than the uninfected controls. Thus, the concentration of curcumin in brain after a single dose of oral PLGA-curcumin (350 μg of curcumin) was significantly higher than that derived from native curcumin (5 mg).Figure 6Estimation of curcumin and its glucuronide in plasma and brain of *P. berghei*-infected and uninfected mice. (**a**) Curcumin concentration in plasma samples. (**b**) Curcumin concentration in brain samples. (**c**) Glucuronide derivative concentration in plasma samples. Discussion {#Sec10} ========== Various formulations of turmeric and curcumin in milk and natural lipids have been described in ancient literature for the treatment of a variety of ailments^[@CR1],\ [@CR2]^. More recent efforts are in terms of using milk proteins and phospholipids to make curcumin nanoparticles to improve stability, bioavailability and efficacy. One such example is the use of β-casein micelle as a nanocarrier to improve the solubility of curcumin. It has been shown that β-casein from camel could increase the curcumin solubility by at least 2500-fold^[@CR28]^. Curcumin liposomes have been prepared using milk fat globule membrane phospholipids exhibiting superior properties in terms of encapsulation efficiency, smaller particle size, slower *in vitro* release etc., compared to native curcumin^[@CR29]^. In another study, curcumin has been encapsulated in milk exosomes and shown to have higher stability in PBS, sustain a harsher digestive process and manifest ability to cross the intestinal barrier than free curcumin^[@CR30]^. A recent study describes the effect of five different formulations of curcumin in milk and indicates higher statistically significant prevention of inflammation in two arthritic rat models. The study also concludes that addition of adjuvants like ghee can enhance the bioavailability of curcumin^[@CR31]^. Such curcumin formulations using natural products need to be evaluated in detail against chemical-based formulations, including nanoformulations, that are reported to enhance bioavailability of curcumin in plasma and improve efficacy mainly in different experimental cancer studies^[@CR32]--[@CR34]^. Among these, PLGA-curcumin is a preferred option, since PLGA polymer is FDA approved for delivery of drugs and functional foods in view of its biodegradability and biocompatibility^[@CR16],\ [@CR17]^. One of the advantages of polymer particle based delivery system is that, when administered orally, it protects the entrapped curcumin from gastric and enzymatic degradation, and hydrolysis. Based on studies with PLGA-curcumin nanoparticles in the rat model, it has been suggested that the increased oral bioavailability may be due to improved water solubility, higher rate of release in the intestinal juice, increased permeability, inhibition of P-glycoprotein-mediated efflux pump and increased residence time in the jejunum^[@CR35]^. While most studies report on the efficacy of PLGA-curcumin in different disease models and cell lines, data on curcumin uptake after administration to animals *in vivo* are scarce. In particular, data on curcumin concentration in the brain when given orally are not available. When PLGA-curcumin was administered intravenously in the rat, curcumin was detected in different organs including the brain, indicating that it can cross the BBB. Nanoformulation was shown to significantly increase the retention time in the cerebral cortex and hippocampus, with curcumin concentrated mainly in the latter site^[@CR36]^. In the present study, the results establish that orally administered curcumin (native as well as PLGA-curcumin) was able to cross the BBB. An interesting feature with PLGA-curcumin treatment was the enhanced and delayed uptake of curcumin in the brain. The small peak (1--2 ng) seen at 45 min was possibly due to the un-entrapped curcumin present. Unlike native curcumin, PLGA-curcumin treatment resulted in a slower build-up of curcumin concentration in the brain giving rise to 3--4 fold increase in the peak after 4 h. PLGA-curcumin maintained the concentration of around 5 ng/g for more than 12 h in brain. It needs to be pointed out that this was seen with 5 mg PLGA-curcumin providing only 350 μg curcumin compared to 5 mg of native curcumin. The lower concentration of curcumin in plasma in case of PLGA-curcumin as compared to native curcumin was because of the lower amount of curcumin release in the initial four hours and rapid metabolism. Once the nanoparticles reached the brain, continuous and enhanced hydrolysis and degradation of low molecular weight polymer and slower metabolism of curcumin in brain as compared to plasma could lead to a slower build-up of curcumin concentration. The use of low molecular weight PLGA for entrapment of curcumin is ideal for slow and sustained build-up of curcumin concentration in brain for more than 12 h. It has been shown that nanoparticles below 200 nm size can cross the tight junction of BBB and can deliver the drugs into the CNS. Even though the size of PLGA nanoformulations used in this study was more than 480 nm, it still showed higher concentration of curcumin in brain when compared to native curcumin. This could be due to the rupture of BBB in case of cerebral malaria infection and use of 1% mannitol as resuspending and cryoprotectant agent during PLGA nanoformulations. This could have helped the PLGA nanoformulation to pass the tight junction and cross the BBB. In terms of therapeutic efficacy, the results obtained in the present study establish for the first time the potential of PLGA-curcumin in the treatment of ECM. The results indicate that PLGA-curcumin was at least as effective as native curcumin in terms of counteracting the breakdown of BBB and reversing all the molecular parameters governing the inflammatory responses seen in ECM. This greater efficacy was seen at 350 µg of curcumin/dose provided by 5 mg of PLGA-curcumin compared to native curcumin provided at 5 mg/dose. Even at this lower concentration PLGA curcumin showed greater efficacy in preventing the sequestration of pRBCs and CD8^+^ T cells in the brain and reducing the levels of IFNγ and IL-10 in serum. However, further studies would be needed to optimize the dose and schedule of PLGA-curcumin administration. It would also be of interest to prepare PLGA-curcumin of different sizes and curcumin load for evaluation. Ghosh *et al*.^[@CR37]^ have prepared nanotized curcumin using a modified emulsion diffusion-evaporation method without the use of polymer matrices and shown that the preparation, when given as a biweekly dose for a month, was more effective at an equivalent concentration than native curcumin in delaying the onset of neurological symptoms and death in mice. The nanotized preparation was also shown to yield high bioavailability by measuring total curcumin in plasma that included the glucuronide and sulfate derivatives. But, data on curcumin levels in the brain and mechanistic details in terms of counteraction of the breach in BBB and sequestration of pRBCs as well as CD8^+^ T cells are not available. In our study, three doses of PLGA-curcumin were shown to completely prevent the onset of neurological symptoms and the delayed death was due to anemia. The results obtained in our study and also reviewed elsewhere^[@CR6],\ [@CR7]^ indicate that curcumin is metabolized very fast to its glucuronide derivative, with free curcumin accounting for a very small fraction of the estimate. Therefore, it would be of interest to measure free curcumin levels in plasma as well as brain with nanotized curcumin and investigate whether the nanotized curcumin can only delay the onset of neurological symptoms in mice as stated by the authors or it eliminates the symptoms completely. In terms of the mechanism of action of curcumin, it needs to be pointed out that most of the studies in literature^[@CR1],\ [@CR8]^ would suggest that inhibition of a variety of molecular targets *in vitro* in cell lines are seen only with concentrations of curcumin in excess of 20 μM. In the present study, curcumin concentration was found to be in the range of 4--15 ng/ml of plasma or g of brain, obtained with a single dose of native or PLGA-curcumin. These concentrations would approximately translate to 10--40 nM. We have also earlier demonstrated the long-term effect of native curcumin in preventing parasite recrudescence in mice^[@CR38]^. We have proposed that curcumin, perhaps, acts through potentiating the mechanisms involved in immune memory to parasite antigens^[@CR5],\ [@CR38]^. Such a mechanism can explain the efficacy of curcumin to bring about changes long after it has disappeared from circulation, be it counteraction of parasite recrudescence in an experimental uncomplicated malaria model or prevent the degenerative neurological changes in the ECM model^[@CR39]^. At the same time, even at nanomolar levels, a 3--4 fold increase in curcumin concentration brought about by PLGA-curcumin elicited a significantly higher potential to counteract the neurological effects seen in ECM than that obtained with native curcumin. Further studies would be needed to understand the unique mechanism of curcumin action. There are a couple of examples where nanocurcumin formulations have been taken further for human studies. One is a commercial preparation referred to as theracurcumin, which contains a highly absorptive form of curcumin with small particle size. This has been shown to decrease serum atherosclerotic low density lipoprotein levels in chronic obstructive pulmonary disease (COPD) patients, an inflammatory disease caused essentially by smoking^[@CR40]^. In another study, Meriva, a commercial curcumin-phosphotidyl choline complex has been shown to significantly improve clinical and biochemical end points in a study with 100 osteoarthritic patients. The standard clinical end point scores were complemented with effect on inflammatory markers such as IL-1β, IL-6, soluble CD40 ligand, soluble vascular cell adhesion molecule-1, and erythrocyte sedimentation rate^[@CR41]^. Thus, the data obtained in our study on ECM with PLGA-curcumin warrant it to be taken forward for evaluation as a potential adjunct therapy to treat HCM. Materials and Methods {#Sec11} ===================== Chemicals {#Sec12} --------- PLGA 50:50, 20 kDa ester terminated, was purchased from Purac, Holland. Curcumin, PVA (30--70 kDa), MTT solution, DMSO cell culture grade and mannitol were purchased from Sigma-Aldrich, USA. Dichloromethane (DCM), acetone and methanol were purchased from Merck India. Uranyl acetate solution and DMEM were purchased from Life technologies, USA, and copper grids were purchased from Polysciences, Warrington, USA. All other chemicals used were of high purity grade available commercially. PLGA-curcumin nanoparticles preparation {#Sec13} --------------------------------------- PLGA-curcumin nanoparticles (PLGA 50:50, 20 kDa) were prepared by single emulsion solvent evaporation method with slight modifications^[@CR42]^. Briefly 300 mg of PLGA polymer and 60 mg of curcumin were dissolved in 5 ml of organic phase (3 ml dichloromethane (DCM) + 2 ml acetone) for 4 h and volume was made up to 5 ml using DCM prior to nanoparticles formation. The organic phase containing curcumin and PLGA was emulsified in 15 ml aqueous phase containing 1% PVA (30--70 kDa) as emulsifier with drop by drop addition and sonication at 40% Watt 20 duty cycle for 3 min (Branson sonifier USA, HD 2200, MS-72 probe) to form O/W emulsion. Similarly, dummy PLGA nanoparticle was prepared without curcumin in organic phase. O/W emulsion formed was subjected to magnetic stirring (150 rpm) for 7 h to ensure complete DCM evaporation at room temperature. After complete evaporation of organic phase, the nanosuspension was centrifuged at 16000 rpm for 15 min. Nanoparticles pellet was washed twice with milli-Q water and resuspended in 5 ml of 1% mannitol solution, lyophilized and stored at 4 °C for further use. PLGA-curcumin nanoparticle characterization {#Sec14} ------------------------------------------- Curcumin nanoparticles were characterized for particle size, zeta potential and polydispersity using Malvern Zetasizer UK (Nano ZS). Briefly, 1 mg of nanoparticles was resuspended in 1 ml milli-Q water and suitably diluted with milli-Q water to avoid multi-scattering. The nanoparticle suspension was vortexed and particle size, zeta potential and polydispersity were measured using nano ZS analyzer in three different batches and the results were expressed as mean + SD. Transmission Electron Microscopy (TEM) {#Sec15} -------------------------------------- Morphology of PLGA-curcumin nanoparticles was analyzed using transmission electron microscope (TEM). Nanoparticle formulations were suitably diluted with milli-Q water, two drops of nanosuspension were placed on copper grid (excess water removed with filter paper) and dried at room temperature for 90 sec. Sample was negatively stained with 1% (w/v) uranyl acetate solution for 30 seconds, dried and observed using TEM (CM 10, Phillips, Holland), operating at 80 kV. Images were obtained using digital imaging software AMT image capture engine (version 5.42.391). Curcumin load and entrapment efficiency {#Sec16} --------------------------------------- Load and entrapment efficiency of curcumin in curcumin nanoparticles was determined by UV visible spectrophotometer. Briefly 10 mg of curcumin nanoparticles was dissolved in 1 ml of DCM and left for 4 h for complete dissolution of PLGA polymer. After 4 h, DCM was evaporated to 200 μl at 37 °C followed by 1 ml methanol addition to precipitate the PLGA polymer. Curcumin was extracted into methanol by centrifugation at 13000 rpm for 10 min at 4 ^◦^C. This process of curcumin extraction by DCM dissolution and methanol extraction was repeated till all the curcumin was extracted. The methanol fractions were pooled and DCM was evaporated at 37 ^◦^C. Curcumin concentration in the extracted methanol was assayed by UV visible spectrophotometer at 420 nm by using the standard graph of curcumin in methanol in the linear range of 5--60 μg/ml. Curcumin load was determined as follows: Load = Curcumin in nanoparticles/total nanoparticles; Entrapment efficiency was determined as follows:$$\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\rm{Entrapment}}\,{\rm{efficiency}}\,( \% )=({\rm{Theoretical}}\,\mathrm{load}/\mathrm{Practical}\,{\rm{load}})\times {\rm{100}}{\rm{.}}$$\end{document}$$ *In vitro* curcumin release study {#Sec17} --------------------------------- *In vitro* curcumin release study was performed with PLGA-curcumin nanoparticles to know the release. Briefly, 20 mg of curcumin nanoparticles were suspended in 20 ml phosphate buffer saline and methanol mixture (PBS: methanol, 9:1 pH 7.4,) (For triplicate 60 mg in 60 ml PBS: methanol) and aliquots were made in 1.7 ml centrifuge tube in triplicates and kept on rotator shaker at 37 °C and 100 rpm. Samples were collected after centrifugation of the nanosuspension at 16000 rpm for 15 min at predetermined time intervals. After complete sample collection, curcumin concentration in the collected samples were determined with the UV visible spectrophotometer using the standard graph of curcumin prepared in the PBS and methanol mixture (PBS: methanol, 9:1 pH 7.4,) at linear range of 1--60 µg/ml. Release study was performed in triplicate on the same nanoformulation batch. Results were expressed as mean + SD. Ethics statement {#Sec18} ---------------- Animals were maintained in accordance with the norms of Committee for the Purpose of Control and Supervision of Experimental Animals (CPCSEA), Government of India (Registration No: 48/1999/CPCSEA) and as approved by the Institutional Animal Ethics Committee (IAEC) of the Indian Institute of Science, Bangalore (CAF/Ethics/102/2007-435 and CAF/ Ethics/192/2010). ECM in mice and curcumin/ PLGA-curcumin treatment {#Sec19} ------------------------------------------------- C57BL/6 mice, 7 to 8 weeks old, were used for the purpose. *P. berghei* ANKA strain (MRA-311, MR4, ATCC Manassas Virginia) was maintained in these mice and 3 × 10^6^ parasitized red blood cells (pRBCs) were injected as described^[@CR13]^. Around 80--90% of the mice manifested neurological symptoms typical of ECM between 7 and 10 days. The animals ended up with coma and in general, died between 10--12 d.p.i. Native curcumin or PLGA-curcumin was given orally in three doses at 24 h interval, starting day 3 post infection. Native curcumin was given in DMSO (5 mg/dose) and PLGA-curcumin as water suspension (5 mg/dose, providing 350 μg of curcumin). The assay procedures carried out were essentially as described earlier^[@CR13]^. Blood-brain barrier permeability and *in vivo* imaging {#Sec20} ------------------------------------------------------ Evans Blue dye was used to assess blood-brain barrier. 0.2 ml of the dye (2% in PBS) was given by i.v. and the staining of the brain was assessed after 2 h. A quantitative measurement was also obtained by extracting the dye from the brain with 100% formamide and the absorbance was measured at 620 nm^[@CR12]^. Whole body and *ex vivo* imaging to assess the sequestration of pRBCs in the brain {#Sec21} ---------------------------------------------------------------------------------- For this purpose, MRA-796 plasmid expressing GFP-luciferase obtained from MR4 (BEI Resources Depository, NIAID, NIH) was transfected into *P. berghei* ANKA strain to obtain a stable transgenic line of *P. berghei*, expressing GFP-luciferase. C57BL/6 was infected with this transgenic *P. berghei* ANKA line (3 × 10^6^ pRBC). D-luciferin (Promega, VivoGloTM) was injected on the days mentioned and bioluminescence of the whole body and head was measured after 10 min. *Ex vivo* imaging of the isolated brain was also carried out as described^[@CR13],\ [@CR43]^. The head and whole body imaging was performed with medium binning factor and field of view (FOV) as 4 cm and 21.8 cm. The exposure time was between 50 --300 sec based on the intensity of the signal. For *ex vivo* imaging of the brain, the animals were sacrificed and the brain was isolated after whole body perfusion. Average radiance (p/sec/cm2/sr) values were calculated for region of interest (ROI) using Living Image® 4.3.1(64 bit) software for experimental and control animals. qPCR analysis for markers of inflammation {#Sec22} ----------------------------------------- Real Time PCR was carried out with 1 µg of RNA isolated from brain (7 d.p.i.) using TRI Reagent (Sigma-Aldrich). ABI StepOnePlusTM System was used. Random hexamers were used for reverse transcription and the cDNA was diluted 1:25 times to carry out Real Time PCR. Housekeeping gene *18s rRNA* was used as endogenous control. The following transcripts were quantified: CXCR3, CXCL9, CXCL10, ICAM-1, TNFα, IFNγ, granzyme B and parasite *18s rRNA*. Uninfected animal CT values served as experimental controls. The relative gene expression levels were calculated by 2^−ΔΔCT^ method. The primers used are listed in Table [S2](#MOESM1){ref-type="media"}. Cytokine and chemokine analysis in serum {#Sec23} ---------------------------------------- ELISA was carried out for the measurement of the inflammatory cytokines IFNγ and TNFα, anti-inflammatory cytokine IL-10 and the chemokine ligand CXCL10 in serum. Murine ELISA kits from BD OptEIATM were used to measure IFNγ and IL-10 levels in 20 µl serum as per manufacturer's protocol. TNFα and CXCL10 levels were quantified using Krishgen Biosystems ELISA kits. Biotinylated detection coupled Avidin-HRP antibodies were used to generate a colored product using 3′,3′,5′,5′ tetramethylbenzidine (TNB) as substrate. The reaction was stopped using 2 N H2SO4. The colored product was measured at A450 using the Infinite 200 PRO TECAN microplate reader. The data provided represent mean + SD from 3 animals in each group. Phospho NF-κB estimation {#Sec24} ------------------------ Western blot analysis was carried out on 7 d.p.i. brain and spleen lysates. Whole organ lysate was obtained by homogenizing brain/spleen in 0.1 M potassium phosphate buffer containing 0.25 M sucrose and centrifuging the homogenate at 14000 g for 20 min. The supernatant (50 μg protein) was used for SDS-PAGE analysis. Western blot analysis was carried out with p-NF-κB antibody (1:1000, CST Rabbit monoclonal \# 3033) and anti-rabbit HRP conjugate. The blots were developed using ECL substrate (Millipore) with ImageQuant LAS 4000 machine. FACS analysis of leukocytes sequestered in the brain {#Sec25} ---------------------------------------------------- Tissue sequestered leukocytes were isolated and processed as described earlier^[@CR43]^. Briefly, brain from uninfected and infected mice (7 d.p.i), were used for the purpose. Brains were harvested from different groups of animals after cardiac puncture and whole body perfusion. Brains were maintained at 4 ^◦^C in the serum containing DMEM media until digestion. Each brain was cut into pieces and digested with 0.05% collagenase D (Roche) and 2U/ml of DNaseI (Thermo scientific) at 37 ^◦^C for 20 min. The tissue extract was sieved through nylon mesh (70 μm) and centrifuged at 400x*g* for 5 min. The pellet was resuspended in DMEM medium and layered on 30% (v/v) percoll (Sigma Aldrich) and centrifuged at 400x*g* for 20 min. The cell suspension was treated with RBC lysis buffer (155 mM NH4Cl, 10 mM NaHCO3, 0.1 mM EDTA, pH 7.3) to remove RBCs. Cell viability was checked using Trypan blue (Sigma Aldrich) and 10^7^ cells were used for flow cytometry. Cell surface staining was performed using conjugated CD3e (clone145-2C11, BD Biosciences), CXCR3/CD183 (clone CXCR3-173, eBioscience), CD8a antibodies (clone53-6.7, BD Biosciences) for 1 h at 4 ^◦^C. Cells were washed with DMEM and fixed with 4% paraformaldehyde followed by PBS wash. Cells were finally suspended in PBS and used for FACS analysis in BD FACS Canto™ II machine. Results were analyzed using BD FACS DIVA™ software. Estimation of curcuminoids in plasma and brain {#Sec26} ---------------------------------------------- Curcumin estimation was carried out as described earlier^[@CR13]^. C57BL/6 mice were given a single oral dose of curcumin or PLGA-curcumin (5 mg/mouse). Plasma or brain samples, fresh or frozen, were processed for curcumin extraction. SPE cartridge (Strata-X 33 μ polymeric reversed phase; 8B-S100-UBJPhenomenex) was used in the case of plasma samples to enrich the phenolics. An LC system (Waters, Corporation, Milford, U.S.A) consisting of an Acquity ultra Performance LC and electrospray chemical ionization tandem mass spectrometer (ESCI-MS/MS; Waters) was used. The samples were separated on Ambient BEH C18 (2.1 × 50 mm), 1.7 μ or Equivalent L1 column. The LOQ for curcumin was 10 ppb. The plasma and tissue sample residue were reconstituted with an appropriate volume of acetonitrile: water containing 0.1% formic acid (1:1) and transferred into a micro-vial. A 5 μl aliquot was injected into LC-MS/MS system and analyzed for curcuminoids and metabolites. Data acquisition and quantitation were performed using MassLynx software version 4.1. These analyses were carried out at Arjuna Natural Extracts, Cochin, India. The samples were coded and analyzed in a blinded fashion. Statistical analysis {#Sec27} -------------------- Paired or grouped statistical tests were carried out according to the sample size. One-way analysis of variance (Bonferroni's Multiple Comparison Test) or Unpaired two tailed t tests were performed using GraphPad Prism 5. Data are presented as mean + S.D. P value summary is mentioned on the bar of each figure. \*P \< 0.05; \*\*P \< 0.001; \*\*\*P \< 0.0001. ns, not significant. Standard survival curve analysis was performed using Kaplan-Meier plot and P values calculated by Log-rank (Mantel-Cox) test. Data availability {#Sec28} ----------------- All data generated or analysed during this study are included in this published article (and its Supplementary Information files). Electronic supplementary material ================================= {#Sec29} Supplementary Information **Electronic supplementary material** **Supplementary information** accompanies this paper at doi:10.1038/s41598-017-10672-9 **Publisher\'s note:** Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. G.P. was supported by Centre of Excellence grant by the Department of Biotechnology, Government of India (BT0i/10/MPB/DT/2010 and BT/PR13760/COE/34/42/2015). G.P. is a NASI-Platinum Jubilee Senior Scientist. A.K.P. was supported by the core grant of the National Institute of Immunology (NII), New Delhi and project grant (BT/PR2426/NNT/289/531/2011) received from the Department of Biotechnology, Government of India. Thanks are due to Dr P.N. Rangarajan for support. C.D. performed animal experiments. J.M. and A.K.P. prepared and characterized PLGA-curcumin nanoparticles. P.N. characterized and maintained mice for ECM experiments. V.A.N. made GFP-luciferase parasite strain. G.P. planned the study. C.D., V.A.N., A.K.P. and G.P. wrote and corrected the manuscript. All authors have given approval for the final version of the manuscript. Competing Interests {#FPar1} =================== The authors declare that they have no competing interests. | Mid | [
0.609289617486338,
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Q: Flex direction property Can somebody please explain why is it important to keep flex direction as column in this case? When you change it to row or row reverse, some portion of the image shrinks in width JS Fiddle: https://jsfiddle.net/fbshqg0c/7/ .main {
width: 100%;
}
.left {
position: relative;
display: flex;
flex-direction: column;
background-color: #fff;
width: 50%;
}
.text {
display: flex;
align-items: center;
}
.text-img-overlay {
position: absolute;
top: 0;
right: 0;
bottom: 0;
left: 0;
padding: 1.25rem;
}
.width100 {
color: #fff;
text-align: center;
width: 100%;
} <div class="main">
<div class="left">
<img src="https://via.placeholder.com/350x150">
<div class="text text-img-overlay">
<div class="width100">
<h1>500x320</h1>
</div>
</div>
</div>
</div> A: That's because the default value for align-items (alignment of secondary axis: Y when direction is row or X when direction is column) property is stretch, so when you use flex-direction: column the image is stretched on the X axis, but when you change it to flex-direction: row then it's stretched on the Y axis (vertical fit, but not horizontal). You have to define width: 100% for the image. | High | [
0.6682134570765661,
36,
17.875
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Yoo Jae Suk, who is already well known for being generous, has donated once more to the elderly 'comfort women' who had suffered through history. He gave 50 million KRW (~ 43,000 USD) to the 'House of Sharing,' where the comfort women reside. The homepage of Gwangju's 'House of Sharing' updated on April 14 with the news of Yoo Jae Suk's donation. He had given 30 million KRW (~ 26,000 USD) toward the construction of the building, 'Human Rights Center for the Comfort Women Victims of Japanese Soldiers,' and another 20 million KRW (~ 17,000 USD) toward the welfare of the comfort women themselves for a total of 50 million KRW. This is not his first time showing his charitable side toward the comfort women. He had donated back in 2014 and 2015. The 'House of Sharing's manager, Ahn Shin Kwon, stated, "Up to now, Yoo Jae Suk has donated a total of 110 million KRW (~ 95,000 USD). He must be busy with his broadcasting activities, but he does not forget to put the elderly comfort women victims first, so we are grateful toward Yoo Jae Suk." | High | [
0.6633663366336631,
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Thursday, October 28, 2010 TriMet union workers picket board meetingFor the second time in a week, union drivers and mechanics publicly protested TriMet’s decision to make them pay into the cost of their medical benefits and freeze their pay. That first sentence says it all. Government workers have been so spoiled that paying a health care premium is outrageous in their minds. I feel bad for the 1% of commuters who like to take three times as long to arrive at their destination if this strike actually happens. Wednesday, October 27, 2010 Took the day off and went duck hunting. To support my hobby I pay the tax on the shotgun, the tax on the shells, the hunting license, the waterfowl validation, the waterfowl stamp, the hunting application fee, the parking permit and the hunting permit fee. In order to be motivated to change their behavior, community members must understand the effects of their transportation choices on overall greenhouse gas emissions and the available alternatives to the single occupant vehicle.(page 34) 19.2. Enact a local ordinance to increase waste recovery rates from commercial and multi-family buildings.(page 40) Your government is going to "educate" you with ordinances, legislation, building codes, taxes, incentives, your electricity supply, your food supply, and the way your cities and neighborhoods are organized. Your government will force you to comply with their idea of what you should eat, what you should drive and how you should live. Your government is coming for your behavior because they don't like your lifestyle choices and they don't like your freedom. Your government wants to achieve "social equity" for the unwashed masses through control of every aspect of our lives. It will be much fairer when everyone has the same small house. Individualized Travel Behavior ChangeThe purpose of an individualized travel behavior change program is to reduce vehicle miles traveled through one-on-one contact with participants in a specific geographical area or in a targeted group. Organizations deliver local transportation information to the target group such as employees, seniors, or students and provide assistance to the participants in exploring travel alternatives. If you don't work for government then you are in the targeted group. Look forward to that "one-on-one" time with a bureaucrat who has decided to get you to walk to work in the rain. Monday, October 25, 2010 I'm seeing an ad for Ron Wyden where a guy talks about how Ron Wyden "brought the research funding" for a private company that allows it to make a product which is "cheaper, smaller" than their competitors product. Maybe it's cheaper because you used taxpayer dollars for your R&D you dimwit. If you can't get private investors to buy into your business plan without taxpayer assistance then maybe your product isn't the whiz bang device you claim it is. And what about your competitors jobs? Did they not get the almighty blessing of Sir Senator Ron Wyden The Great? Did your unfair advantage put them out of business? Ron Wyden didn't create any jobs, he mucked with the free market, a system which has proven to create the best product at the cheapest price. Maybe next Wyden can give taxpayer funds to Motorola to make a phone that is smaller and cheaper than their competitors products. Thursday, October 21, 2010 The Ducks game is a blowout so I came back to the computer after my earlier post. I read CAUSA's blog most days and as usual I'm amused at how indefensible their positions are. The most recent post is regarding illegal aliens and voter fraud. CAUSA insists that it isn't happening. This is like a sex offender advocacy group insisting that their members always register when they get out on parole. Who cares? You are still rapists! The next post is applauding the head of DHS, Bruce Goldberg. CAUSA gives him this reward because as they say "[m]ore than fifty percent of Latinos in Oregon are uninsured." Hooray, our members are all deadbeats, is not exactly a rallying cry in my book. This is what happens when you defend criminal aliens, you are forced to take absurd positions such as "when illegal aliens steal your SSN they are paying into a system that they won't be able to use!" as if that makes the fraud more palatable to the victim. Tri-Met employee highlight: Making a differenceWhether he’s helping a Spanish-speaking rider over the phone, mingling with riders on board a bus, or working with community partners, Martín González—TriMet’s limited English proficiency outreach coordinator—uses his finely-tuned voice of advocacy to help others. I started a search to see what else I could find out about Martin Gonzalez and his salary and one of my first Google results came from a very reputable source: myself. I forgot that back in January of 2008 I reported how $500,000 was being spent on this outreach to our non-English speaking friends. I'm so glad to hear that Mr. Gonzalez is still at the public trough and helping keep Tri-Met crime free. No wait, that would be a security guard. I'm glad that Mr. Gonzalez is helping criminal aliens navigate our taxpayer funded transit system. Thursday, October 14, 2010 Another video from last weekends illegal alien child exploitation march in Salem. They wouldn't be doing this if they didn't think that this was a serious issue. Anchor babies are not politically untouchable because American citizens, who are the government, don't like the current situation. Politically correct politicians may think it's a toxic issue but they won't work for us much longer. Note: Unqualified ineligible noncitizens are referred to as NC1: qualified ineligible noncitizens are referred to as NC2. The income of households with noncitizens is calculated differently based on their alien status. For noncitizens who are not qualified, e.g., foreign students, tourists, or people who are undocumented or who overstayed their visa, a share of their income is excluded. The income is prorated, in order to exclude the noncitizen member’s share. This calculation also applies to households with members who are unable or unwilling to provide the documentation about their immigration status. This category of noncitizens is identified as NC1. Example:A three-person filing group consists of two citizens and one noncitizen who is not eligible for SNAP. The noncitizen pays the $300 per month rent and heating costs for the household. $300 divided by 3 people = $100 share per person. One person is ineligible, so subtract $100 from the $300 and allow the remaining $200 as a shelter deduction for the eligible members. The FUA is allowed as the utility cost. For the same example, if a citizen and the noncitizen were pooling their money to pay the costs, you would prorate only the noncitizen's share. With pooled funds, assume each person pays $150 of the rent. Allow the $150 paid by the citizen. Prorate the NC1's share ($150 ÷ 3 in the filing group = $50 x 2 in the benefit group = $100) for a total Shel deduction of $250. Because utilities are not prorated, allow the FUA. I had a big long writeup of how I think this works but I deleted it because it's very complex. The simple version is that the state of Oregon knowingly gives illegal aliens welfare. That is all. Saturday, October 09, 2010 Stimson Lumber CEO: Oregon on "skull and crossbones list"Miller said he had just returned from an annual meeting that Home Depot hosts for its suppliers, and he explained, as the CEOs and other executives talked with each other, how their "perception of Oregon is incredibly negative." "It isn't that the marginal tax rate is 100 basis points higher in this state than in that state," Miller added. "It's just an attitude around the political leadership that says, 'You just owe us more, and we expect you to do more.'" ...Miller took a whack at House Speaker Dave Hunt, D-Gladstone, saying that "guys like Dave Hunt doesn't want to know me. They're not interested in me, they're not interested in anything I do. But they assume people like me get up in the orning and put capital at risk, hiring people, paying bills, just so they can raise our taxes one more time." Whether you are PGE, McDonald's, or Stimson Lumber at some point I wonder when you will simply "shrug" and decide that you are on strike. Turn off the power, stop providing health insurance and quit making lumber. See if Dave Hunt or Barrack Obama can provide what these businesses always did before the endless government harassment. Employment doesn't happen to provide job statistics for politicians to brag about, employment happens because someone needs help to provide a product or service and you have a willing employer and willing employee. Health insurance isn't provided as a charity, it's part of a willing employees compensation package from a willing employer. Companies don't exist to provide taxes to the public sector, government is a necessary evil which we provide with funds to secure our liberties. Friday, October 08, 2010 New initiative aims to support Latino studentsPortland State President Wim Wiewel on Monday anounced a new program, known as Éxito, to recruit, support and graduate Latino students, who currently make up 5 percent of the student body at PSU. In 2009, Wiewel assembled a task force in order to increase the number of Latino students in higher education. Last June, it released a report outlining key recommendations to achieve this goal, including creating a Latina/o Alumni Association and holding college information sessions for Latino youth and their families. According to Wiewel, the university is committing $350,000 to the initiative, $250,000 of which will come from the university's funds. The other $100,000 will come from the PSU Foundation. Dr. Perla Rodriguez, the principal of Cornelius Elementary School in Forest Grove, said that over 80 percent of the school's student body is Hispanic. Though Rodriguez was born in Oregon, her family moved to the U.S. from Mexico. According to Rodriguez, ethnic students must learn to navigate two cultures at an early age, especially if they wish to succeed academically. However, this often causes conflict, especially when values clash. I almost did this story as a parody where every time the article said "Latino" I was going to put "Asian" or "Irish." I can't stand it when school administrators like Dr. Rodriguez insist that all Latinos are dealing with two cultures. Itspits in the face of American citizenswho get treated like they are different because they happen to have brown skin.Our government has an obligation to treat people as individuals with it's public policy. Wednesday, October 06, 2010 Recall in 2004 what David Wu said about the college attempted rape accusations where it was alleged that he attacked a girl and "tried to stifle her screams with a pillow." This is what he said at the time:"Twenty-eight years ago, I had a two-year romantic relationship with a fellow college student that ended with inexcusable behavior on my part," Wu's statement said. "As a 21-year-old, I hurt someone I cared very much about. I take full responsibility for my actions and I am very sorry." While I'm glad to hear that Wu thought rape was "inexcusable" I still don't like him as a congressman so I've been thinking of some good anti-Wu catch phrases to put on bumper stickers: David Wu: stop holding a pillow over the face of the 1st congressional district while we scream for help David Wu: you ended your college relationship by trying to rape someone, don't do the same to us during your lame duck sessionDavid Wu: just because Clinton was credibly accused of rape and still is politically viable doesn't mean that you are too David Wu: stop attempting to rape our constitution David Wu: you didn't take "no" for an answer when it came to sex but you can't hold a pillow over our votes David Wu: I'm more worried about rapists than Klingons David Wu: opposes the 2nd amendment because it allows rape victims to fight back David Wu: supporting emergency contraception for rape victims because he doesn't want to worry about child support Tuesday, October 05, 2010 A Sample Work Day:A Bilingual Library Assistant may, in this example, start the day at the nearby Migrant Head Start baby classroom sharing early literacy activities (books, songs and rhymes) with children 12 months and under, move to the toddler classroom, followed by activities with preschoolers. Afterward, the Library Assistant may go to the branch, unload the storytime traveling cart and answer questions (in both languages) at the reference desk. Bilingual Library Assistants should be prepared to talk about good books to read, school assignments and community resources. The position should also be ready to provide basic assistance with Internet searching and other library applications. This sample work day may conclude with another hour on the reference desk or giving a tour of the library to a parent group from the local grade school. So for $22/hour plus generous benefits your job is to read books to children, unload a book cart, recommend books and show people how to use Google. A lot ofAmericans are looking for jobs but unless they are bilingual and are "culturally competent" there isn't a position for them in the library. BONUS: See how many times you can find the word "diverse" on the job application webpage! EXTRA BONUS: See how many crimes you can be the victim of in Multnomah County that won't be charged as crimes because the county government "doesn't have the money" to prosecute them! Sunday, October 03, 2010 Thank you for contacting me about certain undocumented minors in the United States. I appreciate hearing from you on this important issue. As you may know, Senator Dick Durbin of Illinois has introduced the Development, Relief, and Education for Alien Minors (DREAM) Act, S. 729. This bill would make undocumented minors eligible to become legal permanent residents provided that they came here as children, have lived in the U.S. for at least five years, have graduated from a U.S. high school, enlist in the military or attend college for at least two years, and have good moral character. When the Senate last considered the DREAM Act, I voted to keep the legislative process moving and to have a full debate on the bill's merits. Unfortunately, the bill was blocked from being considered and during this process several interest groups advanced misconceptions about the bill. The DREAM Act is not amnesty. | Low | [
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Office Depot Every time parents, teachers, and school supporters giveCPSOA ’s ID number when buying supplies at Office Depot, our school receives credits to equal 5% of qualifying purchases to use for FREE SUPPLIES. Purchases made at Office Depot retail stores, on-line, or by phone count towards our account. All you need to do is give CPSOA ’s name or ID number when you purchase at Office Depot retail stores. For on-line orders (www.officedepot.com) or phone orders (1 800 436-3768) please go to the website above to credit CPSOAfor your purchases. | Low | [
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Category: Poetry I am not a huge fan of poetry and I do not really know why. I guess I tend to read novels since I still have to find crime-fiction- poems. Or maybe I should write some myself. Anyway, I have this professor who loves poetry and every time I attend her lessons I wonder why I find it so hard to read poetry when it is so inspiring. Yesterday, we analyzed this poem with her and I fell instantly in love with it. I do not want to write the analysis here, but just its context so that you interpret it yourself and see what it means to you. Eavan Boland writes in 1980’s Catholic Ireland where women’s bodies were silenced. Here it is: ANOREXIC (Eavan Boland) Flesh is heretic. My body is a witch. I am burning it. Yes I am torching ber curves and paps and wiles. They scorch in my self denials. How she meshed my head in the half-truths of her fevers till I renounced milk and honey and the taste of lunch. I vomited her hungers. Now the bitch is burning. I am starved and curveless. I am skin and bone. She has learned her lesson. Thin as a rib I turn in sleep. My dreams probe a claustrophobia a sensuous enclosure. How warm it was and wide once by a warm drum, once by the song of his breath and in his sleeping side. Only a little more, only a few more days sinless, foodless, I will slip back into him again as if I had never been away. Caged so I will grow angular and holy past pain, keeping his heart such company as will make me forget in a small space the fall into forked dark, into python needs heaving to hips and breasts and lips and heat and sweat and fat and greed. Share the literary love: Like this: Hi, everyone, and welcome back to Feminist Sundays! Please leave a link to your wonderful posts on the comments section so that we can all pay you a visit. Thank you :) Feminist Sundays is a weekly meme created at Books and Reviews. The aim is simply to have a place and a time to talk about feminism and women’s issues. This is a place of tolerance, creativity, discussion, criticism and praise. Remember to keep in mind that everyone is entitled to their own opinion, although healthy discussion is encouraged. The idea for this project started when I was reading a book about female philosophers and I realised my total ignorance about their lives, works and achievements. One of the names that came up was Emily Dickinson and of course, I knew her name, but I realised I could not quote a single line of her 1,175 poems. How could that be? So, I decided to dedicate this post to her and to the many other women whose names of course we know, but whose works we are not so familiar with. Name: Emily Dickinson Dates and place: Born in London in 1830 in Amherst, Massachusetts. Died in the same place in 1886. Historical period: Romanticism with an influence of the 18th century metaphysical poets. Famous for: The 1,800 poems discovered by her family after her death at the age of 56. During her short life, she seldom left her house which has resulted in a comparison with the many women secluded in the Middle Ages. Her poetry is usually described as “primitive” due to her scarce use of words, yet hers are masterful pieces full of emotions and images. It is not a simple task for writers to evoke so much through so little. Poems: The Complete Poems (Volume II: Part 3 “Love”). Upon researching her body of work, this has come up as my favourite poem. I like how she established a dialogue and the idea of a legacy where there is a construction around feelings (pain as something you can parcel and put boundaries to). Also, the idea of knowing another person’s consciousness suggests me – probably because of the previous line – eternal love of any kind, not just romantic. But also, a love for someone you know everything about and there is an instant and lasting connection with them. I know this is very little about such a great and well-known writer as Emily Dickinson, but it is a start and this is why I came up with the idea for these posts. I remember studying some of her poems in class and back then the did not appeal to me at all. Now that I have explored her works and I gave myself the opportunity to choose a poem I like and relate to it, Emily has now a place in my mind and heart. Share the literary love: Like this: I must admit I am not the biggest poetry fan. But, ironically, I love music! For me, it is much easier to connect to a message when sung, with music reflecting the singer’s interpretation of the meaning. And talking of music and poetry, yesterday I remembered Carla Bruni and her album No Promises. There, the Italo-French singer adds music to her favourite English poems. My favourite piece of the whole album is Lady Weeping at the Crossroads, a poem from 1940 by W.H Auden full of sadness but, somehow, hope. I think the woman in the poem feels lost but, at the same time, it makes the world hers: there is a sense of infinity surrouding her. So here you have both the original poem and the song. Hope you enjoy it as much as I do! Lady Weeping at the Crossroads Lady, weeping at the crossroads, Would you meet your love In the twilight with his greyhounds, And the hawk on his glove? Bribe the birds then on the branches, Bribe them to be dumb, Stare the hot sun out of heaven That the night may come. Starless are the nights of travel, Bleak the winter wind; Run with terror all before you And regret behind. Run until you hear the ocean’s Everlasting cry; Deep though it may be and bitter You must drink it dry, Wear out patience in the lowest Dungeons of the sea, Searching through the stranded shipwrecks For the golden key, Push on to the world’s end, pay the Dread guard with a kiss, Cross the rotten bridge that totters Over the abyss. There stands the deserted castle Ready to explore; Enter, climb the marble staircase, Open the locked door. Cross the silent ballroom, Doubt and danger past; Blow the cobwebs from the mirror See yourself at last. Put your hand behind the wainscot, You have done your part; Find the penknife there and plunge it Into your false heart. Share the literary love: Like this: Today, in my 19th century literature lesson we read the following poem by Lord Byron and I inmediately fell in love with it. I have a soft spot for certain romantic poems (not any by Cooleridge or Wordsworth) because they appeal very directly to the reader’s feelings. This creates a unique bond between the reader and the author: once again, literature proves ist universality and its power to unite human beings across time and space. Here is the poem: When we Two Parted When we two parted In silence and tears, Half broken-hearted To sever for years, Pale grew thy cheek and cold, Colder thy kiss; Truly that hour foretold Sorrow to this. The dew of the morning Sunk chill on my brow– It felt like the warning Of what I feel now. Thy vows are all broken, And light is thy fame; I hear thy name spoken, And share in its shame. They name thee before me, A knell to mine ear; A shrudder comes o’er me– Why wert thou so dear? They know not I knew thee, Who knew thee so well– Long, long I shall rue thee, Too deeply to tell. In secret we met— In silence I grieve, That thy heart could forget, Thy spirit deceive If I should meet thee After long years, How should I greet thee?– With silence and tears. I happened to had a dream about departing from my boyfriend that same night, so this reading just arose the (unpleasant) feelings I woke up with. But, there is no need for a fictional situation to feel identified with the author’s feelings. However, our professor suggested that this poem is dedicated to Byron’s half-sister, Augusta, with whom he was rumored to have had an affair. Obviously, we (hopefully) cannot identify with the frustration reflected in certain lines (In secret we met / How should I greet thee?) that comes with the relationship, but I also see the pressure from pretending, of abscribing to the English social rules – especially if we take into account Byron’s affairs that would still call our attention even in the 21st century! Share the literary love: Like this: The Canterbury Tales by Geoffrey Chaucer was a compulsory reading for a monographic course on the author. I wasn’t very attracted to the idea at first but I quickly changed my mind. 3/5 Basically, The Canterbury Tales is the transcription of the tales of a group of pilgrims competing for a prize: a soup. It is very important to highlight that it is a transcription and it has a lot of oral features, like interruptions. However, most of the tales rhyme and it is difficult to actually imagine someone speaking like that (even in the 14th century!). Our professor selected some tales for us to read, amounting to 20 in total. However, they could all be linked with one another thanks to their themes or the connection between the narrators. The characters held extensive debates on marriage, sex and appearances versus reality which makes the stories very interesting since each narrator has a different view according to their social class. It is very difficult to actually write a review on the tales: there were some I loved (The Clerk’s Tale) and others I did not really understand because you need to know quite a lot of history/English and French culture to get the references. However, I can assure you they are a great and complete description of the 14th century, its people and how they were affected by the enormous changes of English history (The Peasants’ Revolt, the Black Death). So, I recommend a great book that actually helped me to understand everything better, as a read-along: The Oxford Companion to the Canterbury Tales. It helps if, like me, you choose the Penguin Edition of the tales, translated to Modern English but keeping the rhyming scheme. In general, I enjoyed reading such a classic and I was really surprised to find out that many modern thoughts already existed in Medieval times. For example, Chaucer defends essentialism instead of nominalism: that is, like science, what matters is the facts and not the authority of who says it. Also, some post-modern writing devices were already used back in the 14th century which suggests a long narrative tradition. However, Medieval literature is not really my cup of tea and I found myself struggling with history and Classica literature to understand most of the tales. On the other hand, I think this is the best work for a first approach to English Medieval literature! Click on The Clerk’s Tale above to read a prose translation to Modern English. Share the literary love: Like this: Just recently I did a series on postcolonialism and did not include a wonderful author I did not know yet: Derek Walcott. He is a West Indian with mixed ancestry: two of his grandparents were black and two were white. Being superficial, the result could not be better: he got both blue eyes and dark skin. But, leaving superficial comments besides, his mixed ancestry has also influenced his work as an artist (a decision he took being a kid). However, reading one of his poems, I also found he is very influenced by the sea and the fluidity. This last concept of fluidity is very important in postcolonial theory: we are not fixed entities, we are in continous change and can adapt ourselves to new situations and contexts. Just like water does in different containers! So, I leave here the first poem I read by Walcott, the one I liked the most and that deals with that reconstruction of an African past based on a continent many descendants of slaves have never visited and means nothing to them. Hope you enjoy it. A wind is ruffling the tawny peltOf Africa, Kikuyu, quick as flies,Batten upon the bloodstreams of the veldt.Corpses are scattered through a paradise.Only the worm, colonel of carrion, cries:“Waste no compassion on these separate dead!”Statistics justify and scholars seizeThe salients of colonial policy.What is that to the white child hacked in bed?To savages, expendable as Jews?Threshed out by beaters, the long rushes breakIn a white dust of ibises whose criesHave wheeled since civilizations dawnFrom the parched river or beast-teeming plain.The violence of beast on beast is readAs natural law, but upright manSeeks his divinity by inflicting pain.Delirious as these worried beasts, his warsDance to the tightened carcass of a drum, While he calls courage still that native dreadOf the white peace contracted by the dead. Again brutish necessity wipes its handsUpon the napkin of a dirty cause, againA waste of our compassion, as with Spain,The gorilla wrestles with the superman.I who am poisoned with the blood of both,Where shall I turn, divided to the vein?I who have cursedThe drunken officer of British rule, how chooseBetween this Africa and the English tongue I love?Betray them both, or give back what they give?How can I face such slaughter and be cool?How can I turn from Africa and live? I have added links to the most complicated works so you can read a little bit and understand the poem. Basically, Walcott criticizes both African and European people because they both did the same: end other people’s lives. He also sees his mixed ancestry as something poisoning instead of enriching but still praises the African landscape, separating it from its inhabitants. At the same time, he also praises the English tongue, despite being an important tool of colonialism. I would like to know your opinion about the poem: As I said on my last post, I am a narrative girl, but I’ve discovered a like postcolonial poetry too much. I find it enriching and easier to understand thatnclassical poetry (Whitman, Dickinson etc). So, I have bought an antology on the diaspora poetry called Ten and which I have already recommended to any reader interested in postcolonialism. Did you like the poem? Do you agree with the idea of returning to an African past (unknown to many) as something dangerous? I personally agree with Walcott. Such a return is on a myth and not a reality. I understand that your ancestors being slaves may affect you, but, how can returning to a landscape you don’t know, a language that means nothing to you and to a culture that may be a slight part of you, enrich your life? I would rather focus on the multiculturality of my present and try to enjoy it as much as I can. Share the literary love: Like this: I’ve always considered myself a narrative girl since poetry was never an option. But, things are changing this year because thanks to my Chaucer and Caribbean Literature courses, I am beginning to enjoy poetry. To tell you the truth, I could not be happier! ‘Now listen with good will, as I go straight to my subject matter, in which you may hear the double sorrows of Troilus in his love for Criseyde, and how she forsook him before she died’ Like Romeo and Juliet, or Tristan and Iseult, the names of Troilus and Criseyde will always be united: a pair of lovers whose names are inseparable from passion and tragedy. Troilus and Criseyde is Chaucer’s masterpiece and was prized for centuries as his supreme achievement. The story of how Troilus and Criseyde discover love and how she abandons him for Diomede after her departure from Troy is dramatically presented in all its comedy and tragic pathos. With its deep humanity and penetrating insight, Troilus and Criseyde is now recognized as one of the finest narrative poems in the English language. This is a new translation into contemporary English of Chaucer’s greatest single poem which can be read alongside the Middle English original, or as an accurate and readable version in its own right. First of all I got to admit I got really scared when I realised I had to read one thousand stanzas. How could I do it? I have never enjoyed reading poetry so it just felt a real challenge… but it wasn’t. Troilus and Criseyde has become a work I would consider re-reading in my free time and that has made me love Chaucer’s works a little bit more. The story is very interesting and it is not that different to Romeo and Juliet in that they both deal with an impossible love. In fact, I must admit I love the Chaucerian style over the Shakesperian one (but I cheated, because I read a translation to Modern English). Also, because it is a work from the Middle Ages, there are a lot of intertextuality and interior monologues. Regarding the characters, especially Criseyde, what can I say? She is a modern woman in her own right. Abandoned by her father, she married and there is no reference to her having children. When Troilus approaches her, she has two concerns: her honor and her freedom! In their relationship, she is the strong one, always reluctant to accept Troilus too romantic discourse. Her only blind spot is her fixation on her honor. As a widow, she does not want to be seen with any man and always wears black clothes. Obviously, it is hard to understand but, at the same time, we are still very close in history to the discrimination not only of widows but also of divorced women and single mothers. The love story is difficult to understand for a modern reader. It is based on the idea of courtly love and sometimes the characters have too much affected manners. However, it has the elements of any romantic movie we would be sold nowadays: the boy in love, the strong girl, the funny friend (No Strings Attached comes to my mind right now) and the impossibility of their love. However, some previous reading on courtly love and an open mind will work this problem out. Would I recommend Troilus and Criseyde? Totally! However, readers should keep in mind that the interesting thing of the work is not the ending but how and why the story unfolds as it does. Also, unless you can read Middle English, I recommend to buy the Penguin Edition: the text is translated to Modern English but the stanzas and the rhyme are kept. For those who have read the Postcolonial Series, please keep visiting this post for new aditions as my courses progress. At the moment, I plan to add, at least, one novel, a collection of poems, single poems and a play (their reviews will be post in the main page anyways) Thanks! Share the literary love: Like this: Posts navigation Hi there! My name is Elena. I've always loved reading and writing, and I'm now devoting my life to both. I'm an English and American Literature graduate with a special interest in philosophy, women's studies and crime fiction. You can also find me at: B&R is a Book Depository Affiliate. This means we get 5% of your purchases if you enter the site via Books & Reviews. All profit will be devoted to books | Mid | [
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Provision of psychosocial care for cancer patients: service delivery in urban and rural settings. Although common, psychosocial distress is frequently under diagnosed and untreated in the US health care system. Previous research shows that cancer patients have unmet psychosocial needs, and provision of psychosocial care frequently falls to primary care providers who may lack the resources to adequately deal with complex psychosocial issues. We conducted 25 in-depth key informant interviews with health care professionals working within medical facilities that provide care to cancer patients. Cancer care centers included in the sample were located within both rural and urban communities in a midwestern state, and included providers of both inpatient and outpatient services. Interview questions addressed the assessment of psychosocial needs, availability of psychosocial care, perceptions of the effectiveness of psychosocial services, and perceptions of organizational processes to manage psychosocial needs among their patients. Respondents were also queried regarding recommendations for improving psychosocial care for patients with cancer. Assessment of psychosocial need in most settings was often subjective, not performed, or completed without access to an accepted standardized assessment tool, and clinical pathways to direct psychosocial care were often lacking. Because of the lack of systematic assessment, access to psychosocial care was frequently dependent on the subjective judgment of busy clinicians. This study shows the clear need for organizational and practice redesign initiatives in both rural and urban settings to improve the delivery of psychosocial services to cancer patients. A number of possible system improvements were identified, including the use of allied health providers, standardized screening, and information technology to increase the ease and efficiency of psychosocial assessment. | High | [
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Functional and quantitative analysis of splenic T cell immune responses following oral toxoplasma gondii infection in mice. Functional and quantitative analysis of splenic T cell immune responses following oral Toxoplasma gondii infection in mice. Experimental Parasitology 91, 212-221. Immunity to Toxoplasma gondii is mediated primarily by the host T cell response. Although there is considerable information regarding host immunity following intraperitoneal infection with tachyzoites, little information is available regarding naturally acquired infection following peroral infection with bradyzoites. In this study, a sequential quantitative analysis of the cell-mediated immune response was performed at the single cell level. To assess the kinetics of this response and parasitic loads, inbred mice were orally infected with the 76K strain bradyzoites of T. gondii. Within 24 h of infection, follicular hyperplasia followed by infiltration with histiocytes, macrophages, and apoptotic bodies was observed in the spleens of infected mice. T. gondii were detected from day 1, and counts increased gradually during the experimental period. Splenocyte DNA synthesis to antigen and mitogen was severely suppressed at days 7 and 10. The percentages of NK1.1(+) or delta gamma T cells were increased from day 1, whereas CD4(+) and CD8alpha+ T cells were signficantly increased after day 7 postinfection. CD25 expression and intracellular IFN-gamma production increased in NK1.1(+) cells on day 1 and by all other T cell subsets after day 4. Intracellular IL-4 did not increase until day 7, and IL-10 production was increased in all T cell subsets after day 4. Together, these findings indicate that oral infection with T. gondii stimulates a strong cellular immune response that appears to polarize toward an early Th1 response. However, within 7 days, a strong immune Th2 regulatory response as well as high parasitic loads can be observed, with a reduction in lymphoproliferation to mitogen stimulation, increased production of IL-4 and IL-10, and evidence of T cell apoptosis in the splenic immune compartment. | High | [
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VISA to Test Blockchain Payments among Banks; a SWIFT Rival? VISA and blockchain-technology partner BTL will invite a select group of European banks to participate in a blockchain project that will see inter-bank payments made via transfers over the ledger. Hot on the heels of the likes of R3, Visa will experiment its own blockchain-based payments platform with a select group of banks who will send money over a blockchain. The proof-of-concept project will use Interbit, a cross-border blockchain remittance and settlement platform developed by industry startup BTL.Launched earlier this year, the Interbit platform is seen by Visa as the solution to “reduce cost, settlement time, credit risk, and by leveraging smart contracts to automate many of the regulation and compliance requirements of domestic and international transfers.” BTL estimates that remittance costs can be reduced by over 80% through the Interbit platform, compared to traditional means, such as SWIFT. Hendrik Kleinsmiede, co-founder of Visa Europe Collab, stated: We’re now inviting a small number of European banks to participate in the project alongside us and BTL. Participating banks will be able to connect to the network and send funds to other banks in the network across multiple currencies. The proof-of-concept project is expected to complete the banking experiment within 100 days. Visa has made notable strides to research and develop blockchain technology with various endeavors in recent times. For instance, the world’s largest payments network revealedplans to expand its team of 750 engineers at its technology innovation lab in India. The blockchain-focused technology center is aiming at employing over 1,000 employees before end of 2017, up from 400 engineers during its August 2015 launch. In late 2015, Visa Europe Collab partnered with Epiphyte, a blockchain-based software-as-a-solution (SaaS) provider to develop a proof-of-concept. Earlier this year, Visa published a job posting that sought to hire a senior software engineer to join as a part of its research team to develop a “secure and scalable blockchain” network. Kleinsmiede added: Through the use of smart contracts and blockchains, I believe we can create a fast, compliant and low-cost interbank payment and settlement service, with embedded regional compliance. Blockchain Remittance One of the first known instances of banks using a blockchain to exchange value came to light in early 2016 when R3 revealed an experiment with a total of 11 participating banks, across four continents. Each bank was connected to a private R3-managed ledger, underpinned by Ethereum technology while hosted on a VPN on Azure, Microsoft’s public cloud platform. The successful test ran continuously 24 hours a day for five days in total. In February 2016, a report revealed that JP Morgan Chase, the largest bank in the United States, was discreetly testing U.S. dollar transfers between London and Tokyo with some 2,200 participating clients. JPMorgan is expected to introduce the technology for live transactions later this year. Follow Us on Facebook Join me on Linkedin Subscribe by Email Recent Posts By Samburaj Das for CCN.LA VISA and blockchain-technology partner BTL will invite a select group of European banks to participate in a blockchain project that will see inter-bank payments made via transfers over the ledger. Financial innovation firm R3 has announced the addition of China Merchants Bank (CMB) to its partnership dedicated to designing and applying distributed and shared ledger-inspired technologies (DLT) to global financial markets. In an effort to prove that blockchain technology is not just the preserve of big ticket banking associations, US credit unions have formed a collaborative venture to explore the application of distributed ledgers for member-owned... | Mid | [
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Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension. We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and with the 100-mg dose, it was maintained for 24 hours. Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated (r = .68, P < .01). Renin did not change with the 1-mg dose, but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration. With the 100-mg dose, renin was still elevated twofold 24 hours after dosing. The changes in renin induced by the AT1 receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II. Aldosterone, despite AT1 receptor blockade, did not fall.(ABSTRACT TRUNCATED AT 250 WORDS) | High | [
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THE WAY, WAY BACK is the funny and poignant coming of age story of 14-year-old Duncan’s (Liam James) summer vacation with his mother, Pam (Toni Collette), her overbearing boyfriend, Trent (Steve Carell), and his daughter, Steph (Zoe Levin). Having a rough time fitting in, the introverted Duncan finds an unexpected friend in gregarious Owen (Sam Rockwell), manager of the Water Wizz water park. Through his funny, clandestine friendship with Owen, Duncan slowly opens up to and begins to finally find his place in the world - all during a summer he will never forget. | Mid | [
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Korean sandwich Healthy Bites Ready to discover the creative kitchen of Greenway? This vegan and vegetarian concept aims to offer an alternative to the unhealthy fastfood kitchen with its healthy burgers and other options. This sandwich containing pulled barbecue soy comes with vanilla, kimchi aioli, fresh herbs and a crunchy salad. | Low | [
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Sydney Packard of Georgetown, Mass., Earns All-America and top New England Finish at NCAA Championships Packard's seventh-place time 2:11.05 was also the top New England performance. It is the second consecutive outdoor meet the Engineers have boasted an All-America and it is the program's 10th overall for head coach Brian Chabot. Ohio Northern's Emily Richards repeated as national champion. | High | [
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1. Field of the Invention The present invention relates to a management system, an image forming apparatus, an information processing method, and a storage medium. 2. Description of the Related Art A multifunction peripheral (MFP) utilized in an office includes various functions. More specifically, the MFP like this may include a scan function, a FAX transmission function, and a function for converting scan data into portable document format (PDF) data. These functions are stored on a memory included in the printing apparatus (MFP) as processing programs. A processing program operates according to a user instruction and provides a function requested by the user. In recent years, an MFP has been used that realizes these functions by using a processing program located on a network, via a communication line. For example, if a function for converting scan data into PDF data is located on a network, the following processing is to be executed. Specifically, an MFP, which is installed in an office, scans an original. Then, the scan data is transmitted to the function via a communication line. Subsequently, the function converts the received data into PDF data and temporarily stores the PDF data as a file. Then the PDF file is transmitted to the MFP installed in the office. A conventional management apparatus and a management application (hereinafter collectively referred to as a “management apparatus”) configured to manage a network-connected image forming apparatus (apparatus to be managed) have been used. Japanese Patent Application Laid-Open No. 2007-172274 discusses the following management method. In the conventional method, the management apparatus communicates with the image forming apparatus and acquire information about a function of the image forming apparatus and information about the installation status of an option device installed to the image forming apparatus, such as a paper feed device or a paper discharge device. In the method discussed in Japanese Patent Application Laid-Open No. 2007-172274, information about a function of the option device installed to the image forming apparatus and information about a function included in the image forming apparatus can be acquired. However, in managing an image forming apparatus whose function is located on a network, the availability of a function may vary according to the state of communication between the image forming apparatus and the network-located function, unlike the conventional case of a function locally included in the image forming apparatus. More specifically, although the function information about the image forming apparatus can be acquired by using the conventional management method, if the communication between the device (image forming apparatus) and the function is not available when the function is to be actually utilized, the desired function cannot be utilized. | Mid | [
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Description: In the far future….mankind has been annihilated and the oceans have risen to cover the once daunting landmasses. Now, tribes of sea creatures fight for dominance in the open seas as God intended I think. Lead your squad of fish, crustaceans, marine mammals, and battleships to attack reefs and expand your territory through beam warfare. No real plot, just go out and explore the deep seas. Kill enemy fish, absorb their DNA, and gain their race as an option to use. Take over reefs to have more checkpoints to start from. Every enemy you face is a potential playable unit and they all have their own movesets. | Low | [
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Q: asyncio.run inside sync function returning None Sorry if seems basic, but I really don't understand why this returns None: import asyncio def syncFunc(): async def testAsync(): return 'hello' asyncio.run(testAsync()) # in a different file: x = syncFunc() print(x) # want to return 'hello' how to return 'hello' from asyncio.run? this works but not what I want: def syncFunc(): async def testAsync(): print('hello') asyncio.run(testAsync()) syncFunc() A: why this returns None: Because in your code syncFunc function doesn't have return statement. Here's slightly different version that will do what you want: def syncFunc(): async def testAsync(): return 'hello' return asyncio.run(testAsync()) # return result of asyncio.run from syncFunc # in a different file: x = syncFunc() print(x) | Mid | [
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I went and watched the movie Thor last week. It was entertaining, full of action and laughs, and the lead character – played by Chris Hemsworth – had a pretty incredible transformation – gaining over 20 pounds of lean muscle for the role… And so it has found it’s way onto this blog. After the […] | Low | [
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details Already placed (exclusively) with Ford Paris, new guy Sascha is another gorgeous native of Hamburg, Germany. This thrill seeker, who has Argentinian heritage as well as German, is into bungee jumping and parachuting. With no fear of heights and an incredible look, reaching the model stratosphere ought to be no problem for this very beautiful boy. | Low | [
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MSU's Day 1 draft recap and looking ahead to day 2 Mississippi State first baseman Wes Rea, left, and closing pitcher Jonathan Holder celebrate after a 4-1 win over Oregon State in an NCAA College World Series baseball game in Omaha, Neb., Friday, June 21, 2013. Mississippi State advances to the championship series while Oregon State is eliminated. (AP Photo/Eric Francis)(Photo: Eric Francis AP) Tags Two players associated with Mississippi State heard their names called during the first day of the MLB Draft on Friday. MSU signee Chase Vallot was selected 40th overall by Kansas City. The New York Yankees picked the first current Bulldog with the 55th overall selection. The Royals took Vallot in the competitive balance round A, which follows the first round. The Yankees selected Lindgren with their first pick in the draft, which came in the second round. The southpaw became the third Bulldog in three years to be selected on the first day of the draft. He joined Chris Stratton (2012) and Hunter Renfroe (2013), who were both selected in the first round. Vallot batted .545 as a senior at St. Thomas More High School in Lafayette, Louisiana. He hit .456 in 65 career games with 25 home runs. Lindgren owns a 12-6 record with 189 Ks and a 2.64 ERA during his three seasons in Starkville. As a junior he went 6-1 in his junior year in 26 appearances. He led the team with a 0.81 ERA and opponent's batting average of.124. Both players have until July 18 to sign with their respective professional teams. If terms are not agree upon they can enroll or return to Mississippi State. Today rounds 3-10 begin at noon. Mississippi State could see a host of names fly off the board. Here are a few to watch in rounds 3-10. Brandon Woodruff, P The numbers don't jump out, but his stuff does. Woodruff has always had some of best stuff of any Mississippi State pitcher. Scouts continually lined the front row of Dudy Noble Field hoping to see him pitch. Talent has never been Woodruff's problem. Putting it all together has. He started the season as MSU's ace and finished it as a mop-up duty reliever. He went 1-3 with a 6.75 ERA. He walked 25 in 37 1/3 innings. Jonathan Holder, P When Holder's curveball is on, it's one of the best in baseball. The closer admitted to working on mechanics even up until Mississippi State's final game this season. He had some of his best stuff in the Lafayette Regional. His mid-90s fastball compliments a devastating mid-70s curveball. Holder punched out 71 in 55 2/3 innings this year. He entered the season primarily a three or four-out closer. MSU extended him out recently which should improve his stock. Brett Pirtle, 2B, Nothing jumps off the page when looking at Pirtle's stats. He doesn't have much power (two home runs, 10 doubles). He lacks speed (four stolen bases in nine attempts). But he can hit. In his two years at MSU he hit .337. He led the team this year at .363 – higher than Adam Frazier's a season ago. Frazier was taken in the sixth round last year. Pirtle also is also a plus defender, with good range and is an on-base machine. | Mid | [
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Q: Model opening using ng-repeat My problem is everytime I click on any item pop up opens with first item data instead of the one clicked. Please find code for reference : <div class="quote-inner-section"> <div class="col-xs-6 col-md-6 quote-wrapper" ng-repeat="appreciate in customerQuotes | filter:search"> <div class="quote-wrapper-inner thumbnail" data-toggle="modal" data-target="#myModal" ng-click="modal.selected = clientquote"> <div class="appreciator-snap"> <figure class="appreciator1"> <img src="modules/main/img/icon_user.png" class="img-responsive img-circle" width="35"> </figure> <div class="pointer"></div> <figure class="appreciator2"> <img src="modules/main/img/icon_user.png" class="img-responsive img-circle" width="45"> </figure> </div> <div class="tile-content"> <div class="keymetric-based"> <div class="appreciation-box"> <span class="quote-name" ng-model="writer" ng-bind="appreciate.by"></span> <span class="arrow-right">►</span> <span class="quote-name" ng-bind="appreciate.to"></span> <span class="badge quote-date"> 5 days ago</span> </div> <div class="quote-details"> <blockquote class="truncate"> <p>{{appreciate.description}}</p> <span class = "dotThree">....Read more</span> </blockquote> </div> </div> </div> </div> <div class="modal fade col-md-6 col-sm-6" id="myModal" role="dialog" aria-labelledby="myModalLabel"> <div class="modal-dialog" role="document"> <div class="modal-content"> <div class="modal-header"> <button type="button" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button> </div> <div class="modal-body" > <p>Written by <span ng-model="writer">{{appreciate.by}}</span></p> <p>To <span >{{appreciate.to}}</span></p> <p>Description: <span >{{appreciate.description}}</span> </p> <p>Date : <span> {{date | date:'yyyy-MM-dd'}}</span></p> </div> <div class="modal-footer"> <button type="button" class="btn btn-default" data-dismiss="modal">Close</button> </div> </div> </div> </div> </div> <div class="clearfix"> </div> <nav style="padding-left:15px;"> <ul class="pagination"> <li> <a href="#" aria-label="Previous"> <span aria-hidden="true">«</span> </a> </li> <li class="active"><a href="#">1</a></li> <li><a href="#">2</a></li> <li><a href="#">3</a></li> <li><a href="#">4</a></li> <li><a href="#">5</a></li> <li> <a href="#" aria-label="Next"> <span aria-hidden="true">»</span> </a> </li> </ul> </nav> </div> A: Fixed the issue by adding {{$index}} Updated my HTML as follows : On call : data-target="#myModal{{$index}}" and On model : id="myModal{{$index}}" | Low | [
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#include "stdafx.h" #include "VulkanSwapChainOutputFactory.h" #include "VulkanSwapChainOutput.h" namespace VEngine { namespace Renderer { using namespace VEngine::Renderer::Internal; VulkanSwapChainOutputFactory::VulkanSwapChainOutputFactory(VulkanDevice* device, SemaphoreFactoryInterface* semaphoreFactory) : device(device), semaphoreFactory(semaphoreFactory) { } VulkanSwapChainOutputFactory::~VulkanSwapChainOutputFactory() { } SwapChainOutputInterface * VulkanSwapChainOutputFactory::build(RenderStageInterface * stage) { return new VulkanSwapChainOutput(device, semaphoreFactory, stage); } } } | Mid | [
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Op-eds Corporate Investments Can Help Accelerate Economic Growth in the Developing World: Op-Ed by Ambassador Bloomfield (F80) Many people assume that foreign aid from governments and international bodies is the key driver of economic growth and modernization in much of the developing world. In fact, direct investment by corporations is greater, and increasingly is helping to fill the gap created by declining foreign aid. The 34-nation Organization for Economic Cooperation and Development (OECD) reports that its Assistance Committee distributed $125.6 billion in foreign assistance to developing nations in 2012 -- down from a peak of $128.5 billion in 2010. The United Nations 2013 World Investment Report cites $637 billion in direct foreign investment in developing nations in 2010, and $735 billion in 2011. Corporations are profit-driven, while governments distribute foreign aid both for humanitarian and foreign policy reasons. When conditions in a nation worsen – such as during times of conflict or natural disasters – foreign aid often rises while corporate investment declines due to perceived risk. But corporations have shown that earning profits and helping societies develop are not mutually exclusive activities. Every day, corporations exercise social responsibility, demonstrating that they can serve both their business goals and the public interest… … James Stavridis, who became dean of the Fletcher School of Law and Diplomacy at Tufts University in July following his retirement as a U.S. Navy admiral and his final military tour as the NATO supreme allied commander in Europe, has a reputation for successfully building bridges connecting the public and private sectors around the world as a way to strengthen both security and development. Stavridis advocates “smart power” – the creation of durable partnerships with friends and allies to achieve mutual goals of security, prosperity and peace. He helped develop public-private partnerships that have enabled the U.S. government to work with businesses and non-profits to promote economic development and enable humanitarian assistance as foundations of greater security. Such partnerships enable the government to harness non-governmental expertise to increase the effectiveness of assistance programs. | High | [
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Q: groovy transliteration any language to latin I would like to do transliteration in groovy of a text string UTF to latin characters( for URL purpose). I checked several libs and some are working other not. Currently I'm working with this code: @Grab(group='com.ibm.icu', module='icu4j', version='58.2') import com.ibm.icu.text.Transliterator; String cyrilic = "ш щ ч ц х ф г я "; String id = "Bulgarian-Latin/BGN"; String id1 = "Latin"; String latin = Transliterator.getInstance(id).transform(cyrilic); println "ok : " + latin; String latin1 = Transliterator.getInstance(id1).transform(cyrilic); println "nok : " + latin1; Result ok : sh sht ch ts kh f g ya nok : š ŝ č c h f g â The problem is that I'm not able to detect the correct identifier for a string. I want to do it for an arbitrary language: Japanese, Chinese, German A: Use Any: @Grab(group='com.ibm.icu', module='icu4j', version='58.2') import com.ibm.icu.text.Transliterator; String anything = "ш щ ч ц х ф г я चंब्रिद्गॆ цамбридге كَمبرِدگِ かんぶりでげ"; String id = "Any-Latin"; println Transliterator.getInstance(id).transform(anything); Update per comment: @Grab(group='com.ibm.icu', module='icu4j', version='58.2') import com.ibm.icu.text.Transliterator; String anything = "ш ч с"; String id = "Cyrillic-Latin"; Transliterator.getInstance(id).transform(anything); The code snippet above returns š č s; š in Latin script transliteration result is indeed a representation of the sound of "sh". The same is for č which is "ch". I provided с here to show the distinction that s is returned for it. The rules that ICU4J does Cyrillic-Latin transliteration with is recorded in CLDR project (e.g. see rules for Cyrillic to Latin). To get the output you like to get, you could do another transform with your own customized rules: @Grab(group='com.ibm.icu', module='icu4j', version='58.2') import com.ibm.icu.text.Transliterator; String anything = "ш ч с"; String id = "Cyrillic-Latin"; String myRules = "š>sh; č>ch"; Transliterator myTransliterator = Transliterator.createFromRules("myRules", myRules, Transliterator.FORWARD); myTransliterator.transform(Transliterator.getInstance(id).transform(anything)); which outputs sh ch s. You might also decide to define all your rules for Cyrillic from the scratch if you think that better suit your purpose. | Mid | [
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Roger Craig Smith is my favorite voice for Sonic, and Ryan Drummond comes in second. Jason Griffith was fine in Sonic X, but he was kind of annoying in the games and I don't think Jason Griffith's voice fits Sonic quite as well as Ryan or Roger's voices. I have no idea why anyone likes Jaleel White's Sonic voice, I think it sounds terrible. Roger Craig Smith, Jason Griffith, Jaleel White and Ryan Drummond all give the Blue Blur a unique feeling when they voice or have voiced Sonic, but if I had to pick a favorite, it would be a tie between Jaleel since he was the first and Jason hands down my favorite our of all of them 1. Roger... ROGER... FREAKIN' ROGER.... this man is some kinda Sonic voice actor man. His delivery is always natural, spot on and he provides an entertaining, cool voice for the blue dude. I was sold on his performance in Free Riders, Colors and Gens, but in Lost World.... he just shows the best portrayal of Sonic's character in any game. Towards the end (without too many spoilers), you really do sense Sonic's struggle and I feel pretty sorry for him. I hope he becomes the Jun'ichi Kanemaru of the English cast. 2. Jason Griffith... The man showed his true colors in Secret Rings, Unleashed and Black Knight (coming off the atrocity that was Sonic 06...). Before Roger, he was the first one to give Sonic a slightly older sound to his voice. And while in the first few games where he voiced Sonic, it came off really flat... and I mean REALLY flat. When he improved, he did the writing and Sonic's character in Unleashed and Black Knight justice. 3. Ryan Drummond. He still holds a good place as Sonic's voice imo, but it's easy to see that RCS and Griffith (post 06) surpass him, in terms of acting. Does this mean he's terrible? Hell no. Does it mean he did a great job for Sonic first full fledged voice in a game? Absolutely. Particularly in SA2, he was at his peak. He sounded natural, most of the time, and made Sonic sound hip and with it (....why on earth did I just say that...?). And particularly in the final scene of SA2, with his farewell to Shadow, he showed pretty genuine emotion the whole scene. He was great. @SonicWarrior234 No offense, but I have to disagree with about Roger. In my opinion, he was a downgrade to Sonic's personality. Now, Sonic's just HALF of what he should be. His voice also unfitting for Sonic's age. I mean, he's 15 years old, not 20-30 years old. He's just so average (and somewhat miscast). If anything, I'd always prefer Ryan and Jason over him. Ryan Drummond brought an adventurous Sonic Jason Griffith brought a caring Sonic Roger Craig Smith brought a confident Sonic they all brought something different to the table but they are all good for voicing the Blue Blur. My favorite would have to be Roger though. i was very impressed by his performance. @SteveP Man, that's awful. Having him leave the union? Yikes! I feel bad for Ryan, to be so close to returning to his most famous role, and have it lost because of Sega's unreasonable demands. That was seriously bad of them, like holding a steak up to a dog and yanking it away at the last second. I believe the guy who gave the best performance was Jaleel White, although I don't know if he'd work for a Modern looking Sonic. I like Ryan, but he seemed to be over the top. Martin... sounded like he had a cold. And roger is very good. A little deeper than I'd prefer but a hedgehog has to grow up sometime. A lot of people will disagree with my opinion, but my favorite Sonic voice is Jason. Yeah, sometimes his acting is a little wierd, but for some reason, the voice just clicks. Like, if you played any of these guys, regular people wouldn't know who they're playing, play Jason, and they go, " That's Sonic!" And, overtime, Jason's acting does get better, like in Sonic and the Black knight. I'll just remind you guys this is my opinion and if you don't like it that's great, but that's no reason to start a fan war over it. These are actors, all different and all bring something unique to the character. Who you think is the best is truly based on preference. One thing is for certain, our little blue guy will keep on running for a long time. | Low | [
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McCarthy says he structured #Packers coaching staff with run and pass game coordinators on both sides of the ball because assistants "were a bit restrictive for growth" in the past. "With this new structure, it gives our talented coaches an opportunity to advance within." McCarthy said Pettine was a good fit based on the characteristics he was looking for. Had five things he wanted to focus on in interviews and "Mike nailed them all." Said Joe Whitt had an excellent interview as well. McCarthy says he had five components he was looking for in new defensive coordinator, won't specify what they were. He thought Joe Whitt did a good job addressing those five areas in his interview, but MIke Pettine "really knocked it out of the park." McCarthy already seeing changes in #Packers organizational restructuring: "I've talked to Mark Murphy more in the last three weeks than I did in my first 12 years here. It's been great. Mark's a football man. In his own words, Joe Philbin on what his role was as #Packers offensive coordinator in his last stint, and what he envisions it being this time: "Making Mike McCarthy look like the smartest play caller in the National Football League." Philbin on returning to Green Bay after family tragedy: "It's very, very emotional for all of us, but at the end of the day, we care and love a lot of people here, and a lot of people care about and love us." Philbin said it will be a challenge to break down the offense and find ways to improve an offense that has had success. "How can we score more points? Is it doing more, doing less? Running more, running less?" Philbin says Jim Hostler -- "everybody calls him Hos" -- fits well with his coaching style. Both worked together in Indy. Now, Hostler will be his pass-game coordinator. "We hit it off, thought about football the same way." Mike Pettine said he and McCarthy had mutual friends. Just missed each other at the University of Pittsburgh. Got to spend some time at an owners meeting when I was with Cleveland. Felt like we were in tune. Pettine reiterates exactly what Mike McCarthy has said about "base" defense: "The 3-4, 4-3 debate has really fallen by the wayside." It's a sub league, and #Packers will remain a sub defense. Pettine expects it will be rare to have more than 12-15 "base" snaps most weeks. Pettine said his experience in Seattle was outstanding. Went there in spring and then in training camp and then was able to watch games on film and give advance report on Seattle opponents. Got a chance to really study personnel. Pettine on his defense: "First we're going to be prepared. Scheme is a small part. It starts with fundamentals. I want to make sure guys know scheme is worthless unless you play with emotion and technique. I like to appear multiple without necessarily putting that much in." Pettine said the league has changed and you can't have as many defenses as you once could because of how many young players are on rosters. Used to have 50 defenses, said now 20-25 with all the young players in the league. Asked Mike Pettine if he wants to be head coach again. He says he has no interest. "That's the furthest thing from my mind." When he was HC, Pettine said he missed teaching part of the game. "It's like going from being a teacher to being the principle." Wants to remain a teacher. That's it for the news conference. Check back later today on jsonline.com and packersnews.com for more coverage and analysis of what McCarthy and his new coaches had to say. And stay tuned for Pete Dougherty's weekly chat at 1 p.m. Thursday. | Mid | [
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Q: Graphics Intensive Application in Java I'm making a particle engine in Java, and right now I'm using a subclass of java.awt.canvas. I'm using canvas.getBufferStrategy().getDrawGraphics() and then, when I'm done, using canvas.getBufferStrategy().Show(). Now that I've got some particles (graphics.fillOval(...)) - I need to do some additive blending! Problem is, I can't find additive blending anywhere (googled). What I came up with from a google search is open gl through jogl. jogl would be a great move from graphics, since I have change the graphics color thousands of times a tick, and I can't find additive blending, but I'm just unsure as to whether or not jogl is standard and works on all (or most) computers. Any thoughts or suggestions are welcome. A: You may want to consider AlphaComposite, as shown in this kinetic model. Addendum: This utility may be helpful in visualizing the effect of various compositing rules. | Mid | [
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Matthew McConaughey is super skinny! Matthew McConaughey has gone from "Magic Mike" to minimum Method actor: The guy is so skinny, and it's for a role! The actor, spotted at LAX on Friday, revealed his new shape as he took off his jacket to head through security, according to E! Online. McConaughey has dropped the weight — reportedly 30 pounds off his normal number — to play a man suffering from AIDS and given six months to live in the film "The Dallas Buyers Club." According to IMDb, his character is loosely based on the life of Ron Woodruff, who after being diagnosed with the disease in 1986 and striking out with the one drug then FDA-approved to treat it wound up smuggling alternative drugs into the U.S. for himself and eventually others. The movie, which also stars Jennifer Garner and Jared Leto, is currently filming in New Orleans, where McConaughey's pregnant wife, Camila Alves, visited the set Sunday with their two kids in tow. Expect to see "The Dallas Buyers Club" in theaters in 2013 — but you can peek at a super-skinny McConaughey right now in the video above. | Mid | [
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Bus Rapid Transit UNM / CNM / Sunport Transit Study Bus Rapid Transit (BRT) refers to high-end bus services that provide a fast, comfortable, and convenient way to travel. BRT can include any or all of these features: Sleek, advanced buses that are safe, comfortable, and easier to board. These buses may be branded with a specific logo or identity to distinguish them from regular bus service. Dedicated bus lanes that allow buses to avoid traffic jams, making trips faster and more reliable. Queue-jump lanes that can give buses a head start over cars, reducing the wait time at red lights. Well-designed bus stations that provide shade structures, ticket machines, and real-time arrival information. These stations can be located next to the road or in the median. Stations can also be raised so they are level with the bus floor, allowing people with wheelchairs, strollers, or bikes to roll straight onto the bus. Frequent and fast service so that riders don’t have to wait long for the next bus. Longer hours to allow more people to ride. Here are some examples of how it works in other cities: Eugene, Oregon The Emerald Express (EmX) is a Bus Rapid Transit system linking downtown Eugene to downtown Springfield and including stops at the University of Oregon and Sacred Heart Medical Center. Over 60% of the route consists of dedicated bus lanes, allowing buses to avoid traffic congestion. This increases bus speed and reliability. The bus lanes consist of two concrete tire tracks surrounded by grass, which not only looks good but also allows rain to soak into the ground instead of running off. Many EmX stations are located in the median, allowing passengers to easily travel in either direction, and buses have doors on both sides. Passengers buy their tickets from ticket machines at the stations using cash, debit cards, or credit cards. EmX stations are also raised to be level with the bus floor. This allows people with wheelchairs, strollers, and bikes to roll straight onto the bus, instead of having to use a retractable ramp like on most buses. EmX buses arrive every 10 minutes during the day, 15 minutes during evenings and Saturdays, and 30 minutes on Sundays. After the success of the first EmX line, Eugene opened a second line in 2011, and more are planned. Flagstaff, Arizona Mountain Link is a new bus route connecting Northern Arizona University (NAU) to downtown Flagstaff and nearby residential and commercial areas. The bus runs through the middle of the NAU campus on a street that only allows buses, pedestrians, and bicyclists. Off-campus, the bus shares the road with cars. Buses arrive every 10-15 minutes on weekdays and every 40 minutes on weekends, and real-time data lets riders see exactly where the buses are at any time. Mountain Link carries up to 4,000 riders per day, far more than any other route in Flagstaff. It is jointly funded by NAU and the regional transit provider. El Paso, Texas El Paso recently began construction on a new rapid bus system known as “Brio.” Brio buses will be faster than existing buses and have fewer stops. The bus stations will include shade structures, WiFi internet access, real-time displays telling when the next bus will arrive, and ticket machines so that passengers can pay before they get on the bus. These ticket machines will accept cash, debit cards, and credit cards. Buses will arrive every 10 to 15 minutes and will share the streets with cars. The first Brio line will open in 2014, followed by one new line per year in 2015, 2016, and 2017. Fort Collins, Colorado Fort Collins is currently building a five-mile Bus Rapid Transit “MAX” corridor along Mason Boulevard, connecting downtown, Colorado State University, and other major destinations. MAX will operate in a bus-only lane for most of the route, allowing buses to bypass traffic congestion. Passengers buy their tickets from ticket machines at the stations using cash, debit cards, or credit cards. MAX is the backbone of a larger plan to revitalize the Mason corridor. Fort Collins is building new pedestrian and bicycle paths and using MAX to attract new development to the area, highlighting the economic development potential of Bus Rapid Transit. | High | [
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<!-- NO LONGER USED REPLACED BY UNIFIED Apero-Choix-ImSec.xml (using ${CalPerIm}) --> <Global> <ParamApero> <DicoLoc> <Symb> AeroIn=XXXX </Symb> <Symb> Out=XXXX </Symb> <Symb> PatternAllIm=XXXX </Symb> <Symb> Ext=XXXX </Symb> <Symb> SeuilP3d=1.5 </Symb> <Symb> TetaOpt=0.17 </Symb> </DicoLoc> <SectionBDD_Observation> <BDD_PtsLiaisons> <Id> Id_Pastis_Hom </Id> <KeySet> NKS-Set-Homol@@${Ext} </KeySet> <KeyAssoc> NKS-Assoc-CplIm2Hom@@${Ext} </KeyAssoc> </BDD_PtsLiaisons> <BDD_Orient> <Id> Or-Init </Id> <KeySet> NKS-Set-Orient@${AeroIn} </KeySet> <KeyAssoc> NKS-Assoc-Im2Orient@${AeroIn} </KeyAssoc> </BDD_Orient> </SectionBDD_Observation> <SectionInconnues> <CalibrationCameraInc> <Name>Generate-CalibPerIm</Name> <CalValueInit> <CalFromFileExtern> <NameFile> #### </NameFile> <NameTag> Interne</NameTag> <AutorizeNonExisting>true</AutorizeNonExisting> </CalFromFileExtern> </CalValueInit> <CalibPerPose> <KeyPose2Cal> NKS-Assoc-Id </KeyPose2Cal> <KeyInitFromPose> NKS-Assoc-Im2Orient@${AeroIn} </KeyInitFromPose> </CalibPerPose> </CalibrationCameraInc> <PoseCameraInc> <PatternName> ${PatternAllIm} </PatternName> <CalcNameCalib> Generate-CalibPerIm </CalcNameCalib> <PosValueInit> <PosFromBDOrient> Or-Init </PosFromBDOrient> </PosValueInit> </PoseCameraInc> </SectionInconnues> <SectionChantier> <DirectoryChantier> ThisDir </DirectoryChantier> </SectionChantier> <SectionSolveur> <ModeResolution> eSysL2BlocSym </ModeResolution> </SectionSolveur> <SectionCompensation> <EtapeCompensation> <IterationsCompensation> <SectionContraintes> <ContraintesCamerasInc> <Val> eAllParamFiges </Val> </ContraintesCamerasInc> <ContraintesPoses> <NamePose> .* </NamePose> <ByPattern> true </ByPattern> <Val> ePoseFigee </Val> </ContraintesPoses> </SectionContraintes> </IterationsCompensation> <SectionObservations> <ObsLiaisons> <NameRef> Id_Pastis_Hom </NameRef> <Pond> <EcartMesureIndiv> 1.0 </EcartMesureIndiv> <Show> eNSM_Paquet </Show> <NbMax> 100 </NbMax> <ModePonderation> eL1Secured </ModePonderation> <SigmaPond> 2.0 </SigmaPond> <EcartMax> 5.0 </EcartMax> </Pond> </ObsLiaisons> </SectionObservations> <SectionExport> <ChoixImMM> <ChoixImSec> <KeyAssoc> NKS-Assoc-ImSec@${Out} </KeyAssoc> <PatternSel> .* </PatternSel> <NbMin > 4 </NbMin> <IdBdl > Id_Pastis_Hom </IdBdl> <NbMinPtsHom > 15 </NbMinPtsHom> <TetaMinPreSel> 0.025</TetaMinPreSel> <TetaOpt > 0.17 </TetaOpt> <TetaMaxPreSel> 0.8 </TetaMaxPreSel> <NbMaxPresel> 15</NbMaxPresel> </ChoixImSec> </ChoixImMM> <ExportNuage> <PatternSel> .* </PatternSel> <NameOut> Ori${Out}/Pts3d.dat </NameOut> <ExportNuageByImage> <KeyCalc> NKS-Assoc-Pts3dIm@${Out} </KeyCalc> <SymPts> true </SymPts> </ExportNuageByImage> <PlyModeBin> true </PlyModeBin> <NameRefLiaison> Id_Pastis_Hom </NameRefLiaison> <Pond> <EcartMesureIndiv> 1.0 </EcartMesureIndiv> <EcartMax> ${SeuilP3d} </EcartMax> </Pond> <KeyFileColImage> NKS-Assoc-Cste@NoAttr </KeyFileColImage> </ExportNuage> </SectionExport> </EtapeCompensation> </SectionCompensation> </ParamApero> </Global> | Low | [
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<!-- agents top nav --> <br/> <p>* Adhoc and none adhoc logs will be archived if more than 2 days and deleted after 5 days by daily cron job. Go to <a href="/logs/exploreFiles">Explore Files</a> to check archived logs. </p> | Low | [
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This application also claims the benefit of Japanese Application No. 10-066200 which is hereby incorporated by reference. 1. Field of the Invention The present invention relates to a projection display apparatus having a polarized beam splitter for receiving a light from a light valve and analyzing a modulated light. More specifically, the present invention relates to an improvement on the polarized beam splitter. 2. Description of the Related Art In Published Japanese Patent Registration No. 2599309, disclosed is a color projection display apparatus for separating a light from a light source into respective color lights of R, G and B by a color-separation optical system, making incident each of the color lights on a polarized beam splitter to be polarized and separated, making incident one of lights obtained by polarizing and separating a color light on a reflection light valve arranged for each color light to be modulated, making incident emitted reflected lights including the modulated lights on the polarized beam splitter, analyzing the same and thereby extracting the modulated lights, composing such analyzed modulated lights with one another by a composing optical system and then projecting the composed light by a projection optical system. In FIG. 7, shown is a structure of the projection display apparatus disclosed in the Published Japanese Patent Registration No. 2599309. Specifically, a light emitted from a light source 71 is made incident on a dichroic mirror 72 arranged as a xe2x80x9ccolor-separation optical systemxe2x80x9d on an optical axis. Then, the light is subjected to a color-separation into a B light to be transmitted and R and G lights to be reflected according to a dichroic characteristic of the mirror 72. The transmitted B light is made incident on a polarized beam splitter 74B for the B light as a xe2x80x9cpolarization and separation optical systemxe2x80x9d. An S polarized light of the B light reflected by a polarizing and separating section of the polarized beam splitter 74B is made incident on a reflection light valve 75B. On the other hand, a mixed light of the reflected R and G lights is made incident on a dichroic mirror 73 arranged as a xe2x80x9ccolor-separation optical systemxe2x80x9d on the optical axis in parallel with the dichroic mirror 72. Then, the mixed light is subjected to a color-separation into a G light to be reflected and an R light to be transmitted according to a dichroic characteristic of the mirror 73. The G light obtained by the color-separation is made incident on a polarized beam splitter 74G as a xe2x80x9cpolarization and separation optical systemxe2x80x9d. An S polarized light reflected by a polarizing and separating section of the polarized beam splitter 74G is made incident on a light valve 75G for the G light. Likewise, the R light is made incident on a polarized beam splitter 74R as a xe2x80x9cpolarization and separation optical systemxe2x80x9d. Then, an S polarized light reflected by a polarizing and separating section of the polarized beam splitter 74R is made incident on a light valve 75R for the R light. The S polarized lights respectively made incident on the light valves 75B, 75G and 75R are modulated by signals applied to the same, reflected and emitted as lights including modulated and unmodulated lights. These lights are then made incident on the polarized beam splitters 74B, 74G and 74R for the respective colors, and subjected to an analysis by the polarizing and separating sections of the polarized beam splitters 74B, 74G and 74R. Only the modulated lights are extracted as P polarized lights transmitted through the polarized beam splitters 74B, 74G and 74R, and the analyzed lights are color-composed by a dichroic mirror 76 and a dichroic mirror 77 arranged as a xe2x80x9ccomposing optical systemxe2x80x9d. Then, a result of the color composing is projected to a projection lens 78 as a xe2x80x9cprojection optical systemxe2x80x9d. In the projection display apparatus disclosed in the foregoing Published Patent Gazette, as described above, the dichroic mirrors 76 and 77 are used as the composing optical system. Another apparatus has also been disclosed, where a cross dichroic prism is used as xe2x80x9ccomposing optical systemxe2x80x9d. The inventors of the present invention have investigated a significant problem inherent in the foregoing conventional projection display apparatus, which is constructed in a manner that the reflection light valves 75B, 75G and 75R are arranged for the respective colors, modulated lights among lights reflected by the light valves 75B, 75G and 75R are analyzed by the polarized beam splitters 74B, 74G and 74R arranged for the respective colors and then the analyzed lights are color-composed. Specifically, for an image projected on a screen by the projection optical system (projection lens 78), it was impossible to make registration adjustment (pixel positioning) coincident among the colors. Consequently, pixel deviation occurred. Usually, with reference to the pixel positioning, relative to projected images from one of the light valves 75B, 75G and 75R for specified color lights, pixel deviation of specified positions of the other light valves 75B, 75G and 75R for the other colors must be limited to xc2xd pixel or lower, preferably within ⅓ pixel on full surfaces of the projected images. A level of pixel deviation which is not a problem at all for the conventional light valves 75B, 75G and 75R, each of these having a pixel size of about 40 xcexcm, becomes a severe problem for a light valve having a very small pixel size of about 10 xcexcm. Further, as a projected image is increased in size to be displayed on a large screen, the foregoing problem of pixel deviation will become more severe. The inventors found as a result of extensive investigation that the problem of pixel deviation is not a problem that is created after execution of a vibration test or an environmental test such as a temperature cycle for the projection display apparatus. Rather, this is a basic problem which is created at the time of assembling the constituent members of the projection display apparatus. The inventors found a characteristic of the problem is that although an original shape of the display section of the light valve is rectangular, the display section is deformed to be a parallelogram, and consequently, pixel deviation occurs in a projected light from the light valve for a specified color light. Furthermore, the inventors investigated projected images by replacing, among the constituent members of the projection display apparatus, the members for the respective light colors. When an experiment was made by replacing the polarized beam splitter with another for the other color light and arranging the same, a projected image of another color light was also projected in a parallelogram of the same size. Therefore, it was discovered that the projection of the image in the parallelogram rather than in the original rectangular shape can be attributed to the polarized beam splitter. It is an object of the present invention to provide a projection display apparatus capable of reducing distortion of a projected light. It is another object of the invention to provide a projection display apparatus for enabling registration of pixels of a plurality of light valves. The present invention provides a projection display apparatus which comprises: a modulator including two-dimensionally arrayed pixel units for modulating an incident light and emitting the modulated light; an analyzer for analyzing the emitted light from the modulator; and a projection optical system for projecting the analyzed light from the analyzer. The analyzer includes a polarized beam splitter having a pair of prisms and an adhesive layer held between the pair of prisms. A difference in thickness between thin and thick portions of the adhesive layer is set equal to a predetermined value or lower based on a pixel pitch of the modulator. According to the projection apparatus constructed in the foregoing manner, since a difference in thickness between the thin and thick portions of the adhesive layer is set equal to a specified value or lower based on the pixel pitch of the modulator, an occurrence of pixel deviation after passing through the polarized beam splitter can be prevented corresponding to an accuracy of the pixel pitch, and thus distortion of a projected image can be easily eliminated. Moreover, in the case of the projection display apparatus using the plurality of light valves, accurate pixel registration can be made for each light valve. In accordance with a preferred aspect of the present invention, if a refractive index of the pair of prisms is n1, a refractive index of the adhesive layer is n2, a difference in thickness between the thin and thick portions of the adhesive layer is D and a pixel pitch is P, a value xcex94X is determined by the following expression Δ xe2x80x83 X = D xe2x80x83 ( n 1 2 · n 2 2 - 0.5 · n 1 2 - 1 2 ) and satisfies a following relationship: xcex94X less than (xc2xd)P With the projection display apparatus constructed in the foregoing manner, an occurrence of pixel deviation after passing through the polarized beam splitter can be prevented more effectively. In accordance with a first aspect of the present invention, provided is a projection display apparatus which comprises: a light valve for modulating an incident light and emitting the modulated light; a polarized beam splitter for receiving a light emitted from the light valve and analyzing a modulated light as a light to be transmitted; and a projection optical system for projecting an analyzed light which has been transmitted through and emitted from the polarized beam splitter, wherein the polarized beam splitter has a structure where an adhesive layer exhibiting a refractive index n2 is held between two glass prisms, each of which exhibits a refractive index n1, and if a difference in thickness between thin and thick portions of the adhesive layer is D and a pixel pitch of the light valve is P, a value xcex94X satisfies a relationship of xcex94X less than (xc2xd)P, the value xcex94X being determined by the following expression: Δ xe2x80x83 X = D xe2x80x83 ( n 1 2 · n 2 2 - 0.5 · n 1 2 - 1 2 ) In accordance with a second aspect of the present invention, provided is a projection display apparatus which comprises: a light source; a color-separation optical system for color-separating a light emitted from the light source into R, G and B lights; polarization and separation optical systems arranged for respective color lights obtained by the color-separation of the color-separation optical system, each polarization and separation optical system performing a polarization and separation for a corresponding color light; light valves for the respective color lights, each of which has incident thereon a corresponding one of the polarized lights obtained by the polarization and separation of the corresponding polarization and separation optical system, modulates the corresponding color light, reflects and emits the modulated light; analyzing optical systems for the respective color lights, each of which has incident thereon a corresponding color light emitted from the corresponding light valve and analyzes the modulated light; a composing optical system for color-composing lights analyzed by the analyzing optical systems; and a projection optical system for projecting a light obtained by composing of the composing optical system, wherein the polarization and separation optical systems and the analyzing optical systems are polarized beam splitters arranged for the respective color lights, a polarized light reflected by each of the polarized beam splitters is made incident on the corresponding light valve, and among lights emitted from the light valves, a polarized light to be transmitted is used, and wherein each of the polarized beam splitters has a structure where an adhesive layer exhibiting a refractive index n2 is held between two glass prisms, each of which has a refractive index n1, and if a difference in thickness between thin and thick portions of the adhesive layer is D and a pixel pitch of the light valve is P, a value xcex94X satisfies a relationship of xcex94X less than (xc2xd)P, the value xcex94X being determined by the following expression: Δ xe2x80x83 X = D xe2x80x83 ( n 1 2 · n 2 2 - 0.5 · n 1 2 - 1 2 ) In accordance with a third aspect of the present invention, provided is a projection display apparatus which comprises: a light source; a polarization and separation optical system for polarizing and separating a light emitted from the light source; a color-separation optical system for color-separating one polarized light obtained by polarization and separation of the polarization and separation optical system in the foregoing polarization and separation optical system into R, G and B lights; light valves arranged for respective color lights, each of which makes incident each color light obtained by separation of the color-separation optical system, modulates the same based on a color signal and then emits the modulated light; a composing optical system for color-composing color lights emitted from the light valves; an analyzing optical system for extracting only a modulated light from a composed light obtained by the composing optical system; and a projection lens for projecting a light analyzed by the analyzing optical system, wherein the polarization and separation optical system and the analyzing optical system are polarized beam splitters arranged for respective color lights, a polarized light reflected by each of the polarized beam splitters is made incident on the corresponding light valve, and among lights emitted from the light valves, a polarized light to be transmitted is used as an analyzed light, and wherein each of the polarized beam splitters has a structure where an adhesive layer having a refractive index n2 is held between two glass prisms, each of which has a refractive index n1, and if a difference in thickness between thin and thick portions of the adhesive layer is D and a pixel pitch of the light valve is P, a value xcex94X satisfies a relationship of xcex94X less than (xc2xd)P, the value xcex94X being determined by the following expression: Δ xe2x80x83 X = D xe2x80x83 ( n 1 2 · n 2 2 - 0.5 · n 1 2 - 1 2 ) | Low | [
0.48910891089108904,
30.875,
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Many people like to invest in stock market with their own set of reasons. To some it is a matter of securing sort of personal finance after retirement and to some it a challenging game of easy money. However, very few people actually pay heed to the real concept of stock market and creating a portfolio according to it. And for this accomplishment, it is essential to study the economy impacts of stocks, research on stock and how to buy a stock. In fact, there are two ways to make an investment in stock market -short or long term. And so the functionality of the entire stock depends largely on your overall approach for making cash with the stock market. It is completely on you as to which way you choose. However when it comes to beginners, it is always better to opt for short term. Those who are interested in investing huge amounts and posses a long-term outlook must deal with the big companies including RelianceInd and ONGC. Big companies often do not come up with profitable offers for short-term investors, but long-term investors can stay assured as they surely get a chance to earn profits. These are considered as stable companies where certain amount of profit is almost fixed. There are really two types of investment strategies you can follow-short or long term. Therefore, the stock you decide on largely depends on your overall strategy for making money with the stock market. However, it is widely accepted that the procedure of making some quick money in the stock market through short-term investments is not usually very rewarding. But on the other hand, it is undoubtedly one of the best alternatives for people trying out long-term investments in stock exchange. But the factor of risk sustains in both sorts of trading. Guarantee does not come with any of these two. The market is always fluctuating on momentary basis, showing good augmentation and deft crashes simultaneously. Lets discus on how and in what form should people invest. It is not that one can only invest through the means of shares, which is the most popular kind; you may also invest through bonds and cash. And from starts the heavy confusion of what, where and how to invest. Investors who are conservative by nature must get involved with the investment in cash. These are safe and secured form of investments, where money is rented out on interest comportment through savings accounts, money market accounts, mutual funds, Treasury bills, and Certificates of Deposit. However, a little more avid investors can try with cash and bonds. The risk factor is comparatively more in this sort of investment and so is the amount of profit. Those who are willing to take risk and make quick money they should stick to stock market and can hire some stock market consultant like sharetipsinfo , who can guide there funds in a better way to grow. We have observed people are actually shifting toward stock market in the urge to make quick money however the truth is something else. Stock market is not a game nor any gamble it need hard core analysis and study. Please remember its your money use it wisely don’t invest without proper knowledge or without professionals advice. | Mid | [
0.6359447004608291,
34.5,
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