By adopting a continuation approach, the position analyses of a novel 3-5R parallel mechanism, which has three translation degrees of freedom, are conducted. Next, an equation system of the mechanism structure constraint and an initial equation system are established. Next, a versatile software for solving polynomial equation system is compiled. As giving one displacement, all inverse kinematics are obtained from this software


On 25 May 2002, FriedrichWilhelm Marquardt, Professor Emeritus for Systematic Theology at the Free University (FU) of Berlin, was called out of life, as the death announcement of his family put it, 'in the midst of a happy spring walk'. The readers would have known him above all as a tireless worker for the renewal of the relationship between Christians and Jews. The reflections concerning the encounter between Christians and Jews, the recognition of the shared responsibility of Christians for the National-Socialist murder of the Jews, but also the meaning of the return of Israel to her Land and the founding of the State of Israel were pulled by Marquardt into the center of his Dogmatics perhaps more than by any other Christian theologian. It was a long journey to that point.1


Introduction : Black tea leaf is one of the most important sources of Aluminum in dietary. Therefore this research was conducted to assess the amount of Aluminum in Iranian tea infusion. Methods: To assess Aluminum in Iranian consumed tea, 27 tea samples were analyzed for Al concentration for 10 and 60 min infusion, aluminum concentration was measured with atomic absorption and the results were analyzed by SPSS.13 version. The results showed that minimum and maximum concentration of Al in tea infusion for 10 min infusion was 1.59 and 18.60 mg.L-1 respectively in this regard Baroti and Bamdad tea show the highest and lowest concentration respectively in term of Al, Also Statistical analysis with pair T-test showed that infusion time doesn't significantly effects on aluminum leaching into infusion (P>0.05). Calculation of percentage 'available' Al to the human system showed that 1 L of tea can provide 17.68 % of the daily dietary intake of Al, the percentage 'available' for absorption in the intestine is only 8.49 % for overall mean Al concentration. Conclusion: Therefore based on our results, tea consumption in medium values cannot cause toxic effects on human. Although it is necessary to note that tea consumption might be toxic because of effects on people with absorption or secretion problems.


HIV stands for human immunodeficiency virus, which is the virus that causes HIV infection. The abbreviation "HIV" can refer to the virus or to HIV infection.

AIDS stands for acquired immunodeficiency syndrome. AIDS is the most advanced stage of HIV infection.

HIV attacks and destroys the infection-fighting CD4 cells of the immune system. The loss of CD4 cells makes it difficult for the body to fight off infections and certain cancer Without treatment, HIV can gradually destroy the immune system and advance to AIDS.

This article deals with the Key facts related to the Disease.


Abstract. Long-term monitoring of regulated organic chemicals, such as legacy persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons (PAHs) in ambient air provides valuable information about the compounds' environmental fate as well as temporal and spatial trends. This is the foundation to evaluate the effectiveness of national and international regulations of priority pollutants. Extracts of high-volume air samples, collected on glass fibre filters (GFF for particle phase) and polyurethane foam plugs (PUF for gaseous phase), for targeted analyses of legacy POPs are commonly cleaned by treatment with concentrated sulfuric acid, resulting in extracts clean from most interfering compounds and matrices, and suitable for multi quantitative trace analysis. Such standardised methods, however, severely restrict the number of analytes for quantification and are not applicable when targeting new and emerging compounds as some may be less stable to acid treatment. Recently developed suspect and non-target screening analytical strategies (SUS and NTS, respectively) are shown to be effective evaluation tools aiming at identifying a high number of compounds of emerging concern. These strategies, combining high sophisticated analytical technology with extensive data interpretation and statistics, are already widely accepted in environmental sciences for investigations of various environmental matrices but its application to air samples is still very limited. In order to apply SUS and NTS for the identification of organic contaminants in air samples, an adapted and more wide-scope sample clean-up method is needed, compared to the traditional method which is using concentrated sulphuric acid. Analysis of raw air sample extracts, without clean-up, would generate an extensive contamination of the analytical system with especially PUF matrix-based compounds and, thus, highly interfered mass spectra and detection limits which are unacceptable high for trace analysis in air samples. In this study, a novel wide-scope sample clean-up method for high-volume air samples has been developed and applied to real high-volume air samples, which facilitates simultaneous target, suspect and non-target analyses The scope and efficiency of the method was quantitatively evaluated with organic compounds, covering a wide range of polarities (logP 2-11), including legacy POPs, brominated flame retardants (BFRs), chlorinated pesticides and currently used pesticides (CUPs). In addition, data reduction and selection strategies for SUS and NTS were developed for comprehensive two-dimensional gas chromatography separation with low resolution time-of-flight mass spectrometric detection (GC×GC-LRMS) data and applied on real high-volume air samples. Combination of the newly developed clean-up procedure and data treatment strategy enabled the prioritisation of over 600 compounds of interest in the particle-phase (on GFF) and over 850 compounds in the gas-phase (on PUF), out of over 25 000 chemical features detected in the raw data set. Of these, 50 individual compounds were identified and confirmed with reference standards, 80 compounds were identified with a probable structure and 774 compounds were assigned to various compound classes. In the here available dataset, 11 hitherto unknown halogenated compounds were detected. These unknown compounds were not yet listed in the available mass spectral libraries.


Introduction: In the current era of comprehensive medical care in adults with sickle cell anemia (SCA), median survival is 48 years of age (Blood, 2019 Feb 7;133(6):615-617) with cardiopulmonary disease being a major cause of mortality. Despite lung disease being a major cause of death in young adults with SCD, no evidence-based guidelines are available to follow adults with SCD with pulmonary function tests (PFT). In addition to lung disease being a major cause of earlier death, we demonstrated forced expiratory in 1 second percent predicted (FEV1%) was associated with increased probability of premature death (hazard ratio per % predicted 1.02; 95% confidence interval [CI] 1.00-1.04; p=0.037) in a prospective cohort of young adults with SCA (n=430), with a mean age of 32.6 years (Blood, 2015 vol. 126(13) pp. 1544-50).
 To provide additional evidence that lung function surveillance should be part of standard care for adults with SCD, we elected to compare the FEV1 volume loss in young adults with SCD to FEV1 volume loss in young adults with cystic fibrosis (CF). We selected CF because this disease is a well-established genetic disease where cardiopulmonary complications are the major cause of death. We tested the hypothesis that older adults with SCD (> 30 years of age) would have an absolute change per year in FEV1 similar to older adults with CF. If the results support the hypothesis, such a finding would provide additional evidence that monitoring decline in FEV1 in adults with SCD may lead to more targeted approaches for decreasing mortality.
 Method: In a retrospective cohort study design conducted at Vanderbilt University Medical Center, we evaluated the electronic records of adults with SCD and CF. Individuals with either disease must have had at least 2 pulmonary function tests (PFTs) to be included. The absolute change in the FEV1 values was analyzed and compared between the groups. Adults with SCD received PFT evaluation at least once every two years as standard care. Only the first PFT in each year was used for adults with CF and evaluation could not be done within eight weeks of a hospital admission. A multivariable mixed model regression analysis was used to predict change over time in at least 2 spirometry evaluations with a pre-specified set of covariates previously associated with FEV1 decline in SCD or CF.
 Results: A total of 180 and 234 adults with SCD and CF, respectively, with a mean age of 25.1 and 31.0 years, respectively, were included (see Table 1). The mean duration of follow up for adults with SCD and CF was 4.7 and 7.3 years, respectively. Using a multivariable mixed model regression analysis after adjusting for the statistically significant covariates (sex, SCD phenotype, and height for SCD; and sex, pancreatic insufficiency, and height for CF), the rate of FEV1 decline in individuals with SCD and CF over 30 years of age was 28 ml (p<0.001) and 30 ml (p<0.001) per year, respectively (p<0.001), These rates of decline were not different between the adults with SCD and CF (p=0.636), as shown in Figure 1. The rate of FEV1 change in individuals with SCD and CF between 18 and < 30 years of age was an increase of 10 ml per year (p=0.074) and a decrease of 64 ml per year (p<0.001), respectively (p=0.003).
 Conclusion: Our results provide clear evidence that adults > 30 years of age with SCD have a rate of decline of FEV1 similar in magnitude to adults with CF greater than 30 years of age. Our new findings, coupled with our prior results indicating that lower FEV1% predicted was associated with earlier mortality in young adults with SCD, provide clear evidence that surveillance of FEV1 decline is warranted and therapeutic trials are needed if we are going to address all of the risk factors for attenuated life-span in adults with SCD.

 No relevant conflicts of interest to declare.


In this research an attempt has been made to fully characterize a diodes array in shunt configuration as ESD protection circuit in order to maximize ESD performance of the products in IBM SOI 0.18um technology. For full characterization of ESD protection of RF circuit, HBM and TLP tests and simulation have been conducted and discussed in detail. Test results for HBM and TLP are summarized and grouped according to their stack number. Simulations on HBM and TLP were carried out using Cadence Spectre environment and compared to the tests for HBM and TLP obtained using Celestron I. To consider the RF part, small signal analysis and large signal analysis are done in Advanced Design System. Small signal extracts the black box capacitance using S-parameter in ADS and compares with test results obtained using Murray Microwave system. Also large signal analysis is carried out to see the nonlinearity of the ESD protection device. In large signal analysis input power is swept and output power is observed on different harmonics caused by the inherent nonlinearity of the device. Again large signal simulation results were compared with test results obtained from Murray Microwave System. Lastly, this research has been conducted to fully characterize the diodes array as ESD protection in shunt configuration and to produce a predictive ESD model.


ABSTRACT The growth phase-dependent activity profile of the alternate transcription factor ςB and its effects on the expression of sar and agr were examined in three differentStaphylococcus aureus strains by Northern blot analyses and by the use of reporter gene fusion experiments. Significant ςB activity was detectable only in the clinical isolates MSSA1112 and Newman, carrying the wild-type rsbU allele, but not in the NCTC8325 derivative BB255, which is defective inrsbU. ςB activity peaked in the late exponential phase and diminished towards the stationary phase when bacteria were grown in Luria-Bertani medium. Transcriptional analysis and a sarP1-sarP2-sarP3(sarP1-P2-P3)-driven firefly luciferase (luc+) reporter gene fusion demonstrated a strong ςB activity- and growth phase-dependent increase in sar expression that was totally absent in either rsbU or ΔrsbUVWsigB mutants. In contrast, expression of theagr locus, as measured by RNAIII levels and by anhldp::luc+ fusion, was found to be higher in the absence of ςB activity, such as inrsbU or ΔrsbUVWsigB mutants, than in wild-type strains. Overexpression of ςB in BB255 derivatives resulted in a clear increase insarP1-P2-P3::luc+ expression as well as a strong decrease in hldp::luc+ expression. The data presented here suggest that ςBincreases sar expression while simultaneously reducing the RNAIII level in a growth phase-dependent manner.


We propose and demonstrate a cost-effective 112 Gb/s optical transceiver based on dual carrier-DQPSK with direct detection. The performances of DC-DQPSK are evaluated by transmitting 112 Gb/s signal over 480 km of SMF link carrying 10 Gb/s NRZ neighboring channels.


Consumer acceptance of new food technology, like genetically modified food, is essential for the product's success. Consumers have been skeptical toward the technology of genetically modified food due to lack of knowledge by the public, negative portrayal of the technology by the media, and a lack of communication about the technology from those who develop and use it. This research was guided by the Elaboration Likelihood Model to investigate the influence of persuasive communication on Florida consumers' attitude toward genetically modified food. Consumers typically use the peripheral route to assess food information, therefore a message source (peripheral cue) was manipulated to examine its effect on attitude. An experimental design administered through an online survey was used to collect data (n = 515). Respondents reported that they agreed they were knowledgeable about genetically modified food, but they were unsure about associated risks. Respondents neither agreed nor disagreed that the four sources were credible, and there were no differences in credibility. Additionally, there were no differences in their attitude toward genetically modified food associated with the source. The results showed that the source did not predict attitude, but source credibility, risk perception, and some demographic characteristics did. Prior knowledge was not a predictor of attitude, and the respondents likely used the peripheral route to assess the message. Agricultural communicators should target communication for specific audiences and deliver value-driven messages rather than trying to increase consumer knowledge alone. Future research should explore different peripheral cues and their effects on attitude formation.


Objective: To determine the impact of WhatsApp Messaging on learning paediatrics during clinical rotation of final year MBBS medical undergraduates.
Study Design: Quasi-Experimental study
Place and Duration of Study: Bahria University Medical and Dental College, Karachi Pakistan, from Apr to Oct 2018.
Methodology: Final year MBBS students attending the Department of Paediatrics for three months of clinical rotation were randomly allocated to two Groups. Group-A was the control Group without WhatsApp, and Group-B was the intervention Group with WhatsApp messaging. Both Groups had a pre-test and post-test before and after their clinical rotation. The evaluation was performed before and after clinical rotation using Multiple choice questions (MCQs) for the final evaluation.
Results: Of a total of 80 students, 19(23.8%) were males, and 61(76.3%) were females, with a median age of 23(22-23) years. Of 40 students in the WhatsApp Group, active participation was observed in 37(92.5%) students, whereas the quality of the shared content by students was found to be adequate/relevant in 35(87.5%) cases. The median score was significantly higher in both Groups' clinical rotation test than in the pre-clinical rotation assessment (p-value <0.001). However, the median score of the post-clinical rotation test was significantly higher in the WhatsApp Group than in the non-WhatsApp Group (p-value <0.001).
Conclusion: WhatsApp was found to be a highly effective tool for learning paediatrics among medical students during their clinical attachment.


This paper deals with the one-dimensional Green–Naghdi equations describing the behavior of fluid flow over an uneven bottom topography depending on time. Using Matsuno's approach, the corresponding equations are derived in Eulerian coordinates. Further study is performed in Lagrangian coordinates. This study allowed us to find the general form of the Lagrangian corresponding to the analyzed equations. Then, Noether's theorem is used to derive conservation laws. As some of the tools in the application of Noether's theorem are admitted generators, a complete group classification of the Green–Naghdi equations with respect to the bottom depending on time is performed. Using Noether's theorem, the found Lagrangians, and the group classification, conservation laws of the one-dimensional Green–Naghdi equations with uneven bottom topography depending on time are obtained.


The two-receiver Gaussian broadcast channel is a model of a communication system where a single codeword is transmitted over two distinct Gaussian channels that have different signal-to, noise ratios. The receiver with the better signal-to-noise ratio decodes all of the information carried by the codeword, while the other receiver decodes only some of the information. The concept of group codes for the Gaussian broadcast channel is developed and applied to permutation codes for the Gaussian broadcast channel. A group code for the Gaussian broadcast channel is a group code for the single-user Gaussian channel in which a subgroup of the generating matrix group is used to partition the codewords into disjoint subsets called clouds. Distinct clouds represent distinct messages for the noisier channel while the individual codewords represent distinct messages for the other channel. The clouds share some of the distance properties of group codes. Necessary and sufficient conditions are given for finding good group codes for the Gaussian broadcast channel (in terms of minimum distance).


Rationale: Repetitive transcranial magnetic stimulation (rTMS) is used alone or in combination with physiotherapy for rehabilitation of stroke patients. TMS mapping can also quantify the excitability of the motor area in both the ipsilesional (IL) and contralateral (CL) hemisphere. Objective: This study is the first to measure the dynamics of cortical excitability by TMS mapping before and after treatment with low-frequency (LF) rTMS in the contralesional hemisphere at three different timepoints. Furthermore, the patients were clinically evaluated during the same visit as the mapping to establish both short and long-term outcomes after rTMS treatment. Methods and Results: A total of 16 participants with acute ischemic stroke were assessed 10 days post-stroke by TMS mapping. The patients were randomized into two equal groups: a real rTMS group and a sham group. The rTMS group received LF-rTMS to the contralesional hemisphere for 10 days, starting on the first day after the first mapping. Each subject was also evaluated by mapping on days 45 and 90 after stroke onset. The primary clinical outcome measured was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) on days 10, 45 and 90 post-stroke. At 10 days after stroke onset, both groups presented low excitability in the lesion side and high excitability in the non-affected side. In the real rTMS group, at 45 days after stroke, a downward trend in the excitability of the contralesional hemisphere and an upward trend in the excitability of the lesioned side were observed. At 90 days after stroke, a tendency toward balanced excitability between both hemispheres was observed. In the sham group, at both 45 and 90 days, we observed increased excitability in the non-affected side compared to the side with the lesioned motor area. At 45 days, the real rTMS group demonstrated a better recovery of the upper limb motor function than the sham group, but at 90 days, there was no significant difference between the two groups. Discussion:These results demonstrated that LF-rTMS treatment enhances rebalance of the excitability patterns in both hemispheres and led us to question the "one size fits all" approach widely used in rTMS interventions. Abbreviations: Amax = maximum amplitude, Amean = AM = averaged amplitude, APB = abductor pollicis brevis, CL = contralesional, DTI = diffusion tensor imaging, EEG = electroencephalography, EMG = electromyography, FMA-UE = Fugl-Meyer Assessment for Upper Extremity, HS = hot spot, IHC = interhemispheric functional connectivity, IL = ipsilesional, LF-rTMS = low-frequency repetitive transcranial magnetic stimulation, MCA = middle cerebral artery, MEP(s) = motor evoked potential(s), NIBS = non-invasive brain stimulation, rMT = resting motor threshold, RP = responsive points, rTMS = repetitive transcranial magnetic stimulation, TMS = transcranial magnetic stimulation


An early form of procollagen I was found in acetic acid extracts of radioactively labeled chick embryo skull bones. It resembled native procollagen I, but sedimented slightly faster, and its component chains were slightly underhydroxylated and were not disulfide-linked to each other, although its propeptides were internally disulfide-bonded. Pulse-chase experiments showed its conversion to disulfide-linked procollagen. As the same conversion occurred when proline hydroxylation was blocked by 2,2'-dipyridyl, we infer that the formation of this precursor from its component chains does not require collagen triple helix formation. We suggest that interaction between the folded carboxyl propeptides of individual pro-alpha (I) chains is an important step in the formation of this precursor and of procollagen I. Studies of the refolding and association of fully reduced and denatured carboxyl propeptides supported this concept. In the presence of glutathione the correct disulfide bonds could be reestablished, as judged by a mapping of some tryptic peptides. Individual carboxyl propeptides refolded first, and this occurred even in 2 M urea. Recognition between folded carboxyl propeptides occurred only when less than 0.5 M urea was present. The presence of the carboxyl telopeptides was important for trimeric reassembly. Individual propeptides also folded spontaneously during cell-free translation of pro-alpha (I) chains and were recognized by specific antibodies. We consider the role of carboxyl propeptides in the formation of procollagen I molecules and suggest a model of self-assembly, possibly facilitated by interactions with the luminal surface of the rough endoplasmic reticulum.


Success is making a difference in wealth is the longing of every human being in general and believers in particular. Everyone longs for unity. However, the reality of conflict often occurs both within the family, in the church, and in the life of the nation. One of the causes of conflict is due to not being able to manage differences. The differences in question are differences in religion, ethnicity, culture, education, and so on. If these differences are not managed properly, conflicts will continue to exist both within the family, in the church, and in the life of the nation. Seeing the situation as described above, a theory is needed on how to manage differences into wealth. This article will provide a theory on how to manage the differences to become wealthy. This theory is an analysis of Colossians 3: 12-17.


A novel copper-catalyzed three-component reaction of monofluoroalkylation agents, alkenes and TMSCN is described. In addition, alkynes could also be compatible with the reaction system to obtain three-component products for the first time with moderate yield and excellent E/Z stereoselectivity. This reaction provides a facile method for the synthesis of cyanomonofluoroalkyl compounds, which may serve as potentially useful organic intermediates for further transformations. Preliminary mechanistic investigation indicated that monofluoroalkyl free radicals were involved in the cyanomonofluoroalkylation process.


Pulmonary symptoms are the primary manifestation of the COVID-19 disease, which originated in Wuhan in China in December 2019. However, it is now established to show widespread extrapulmonary manifestations, including gastrointestinal involvement. Abdominal pain, diarrhea, nausea, and vomiting are considered the most common gastrointestinal symptoms. Gastric perforation in association with COVID-19 is rarely reported in the literature. Here, we report a case of a 71-year-old male COVID-19-infected patient, medically free, who presented to the emergency department complaining of severe abdominal pain for a one-week duration. He was diagnosed with a case of perforated viscus and septic shock. The patient was shifted to the operating room for exploratory laparotomy. We aim in this report to highlight this fatal complication of COVID-19 infection in order to improve patients' outcomes.


We report the discovery of PSR J0952−0607, a 707 Hz binary millisecond pulsar that is now the fastest-spinning neutron star known in the Galactic field (i.e., outside of a globular cluster). PSR J0952−0607 was found using LOFAR at a central observing frequency of 135 MHz, well below the 300 MHz to 3 GHz frequencies typically used in pulsar searches. The discovery is part of an ongoing LOFAR survey targeting unassociated Fermi-Large Area Telescope γ-ray sources. PSR J0952−0607 is in a 6.42 hr orbit around a very low-mass companion ( ), and we identify a strongly variable optical source, modulated at the orbital period of the pulsar, as the binary companion. The light curve of the companion varies by 1.6 mag from at maximum to , indicating that it is irradiated by the pulsar wind. Swift observations place a 3σ upper limit on the X-ray luminosity of erg s−1 (using the 0.97 kpc distance inferred from the dispersion measure). Though no eclipses of the radio pulsar are observed, the properties of the system classify it as a black widow binary. The radio pulsed spectrum of PSR J0952−0607, as determined through flux density measurements at 150 and 350 MHz, is extremely steep with (where ). We discuss the growing evidence that the fastest-spinning radio pulsars have exceptionally steep radio spectra, as well as the prospects for finding more sources like PSR J0952−0607.


In this paper we propose the mutable consensus protocol, a pragmatic and theoretically appealing approach to enhance the performance of distributed consensus. First, an apparently inefficient protocol is developed using the simple stubborn channel abstraction for unreliable message passing. Then, performance is improved by introducing judiciously chosen finite delays in the implementation of channels. Although this does not compromise correctness, which rests on an asynchronous system model, it makes it likely that the transmission of some messages is avoided and thus the message exchange pattern at the network level changes noticeably. By choosing different delays in the underlying stubborn channels, the mutable consensus protocol can actually be made to resemble several different protocols. Besides presenting the mutable consensus protocol and four different mutations, we evaluate in detail the particularly interesting permutation gossip mutation, which allows the protocol to scale gracefully to a large number of processes by balancing the number of messages to be handled by each process with the number of communication steps required to decide. The evaluation is performed using a realistic simulation model which accurately reproduces resource consumption in real systems.


Surgical removal of colorectal cancer (CRC) liver metastases generates areas of tissue hypoxia. Hypoxia imposes a stem-like phenotype on residual tumor cells and promotes tumor recurrence. Moreover, in primary CRC, gene expression signatures reflecting hypoxia and a stem-like phenotype are highly expressed in the aggressive Consensus Molecular Subtype 4 (CMS4). Therapeutic strategies eliminating hypoxic stem-like cells may limit recurrence following resection of primary tumors or metastases. Here we show that expression of DNA repair genes is strongly suppressed in CMS4 and inversely correlated with hypoxia-inducible factor-1 alpha (HIF1α) and HIF-2α co-expression signatures. Tumors with high expression of HIF signatures and low expression of repair proteins showed the worst survival. In human tumors, expression of the repair proteins RAD51, KU70 and RIF1 was strongly suppressed in hypoxic peri-necrotic tumor areas. Experimentally induced hypoxia in patient derived colonospheres in vitro or in vivo (through vascular clamping) was sufficient to downregulate repair protein expression and caused DNA damage. Hypoxia-induced DNA damage was prevented by expressing the hydroperoxide-scavenging enzyme glutathione peroxidase-2 (GPx2), indicating that reactive oxygen species mediate hypoxia-induced DNA damage. Finally, the hypoxia-activated prodrug Tirapazamine greatly augmented DNA damage and reduced the fraction of stem-like (Aldefluorbright) tumor cells in vitro, and in vivo following vascular clamping. We conclude that decreased expression of DNA repair proteins and increased DNA damage in hypoxic tumor areas may be therapeutically exploited with hypoxia-activated prodrugs, and that such drugs reduce the fraction of Aldefluorbright (stem-like) tumor cells.


Introduction: TP53 is the most frequently mutated gene across all cancers at approximately 50% and in cancers such as high grade serous ovarian up to 96%. In addition to the high incidence of DNA mutations at the gene locus, the TP53 pathway is also dysregulated through alternative mechanisms which involve other members of the regulatory cascade such as overexpression of Mdm2 or Mdmx. In contrast to other tumor-suppressors, TP53 possesses a spectrum of mutations including both loss and gain of function. Some mutations such as E177R result in a partial loss of TP53 function, eliminating the apoptotic fate while retaining senescence and cell-cycle arrest. Despite the centrality of TP53 in cancer, its prognostic significance remains unclear and the development of targeted therapies is ongoing. Characterizing TP53 mutation status in conjunction with transcriptional profiling of tumor biopsies will enable a more comprehensive understanding of the functional consequences of different classes of TP53 mutations and aid in distinguishing partial from total abrogation of TP53 pathway function. Asuragen has developed sensitive assays and algorithms to characterize DNA mutations and RNA expression profiles from the most challenging poor quality clinical samples. In order to enable a more complete understanding of the functional consequences of TP53 mutations (or lack thereof), we present an application of these approaches to characterize TP53 function in FFPE ovarian cancer biopsies through an integrated analysis of DNA and RNA sequencing. Methods: Primary FFPE tumor biopsies were collected from a cohort of 200 paclitaxel/carboplatin resistant ovarian cancer patients. DNA from isolated tumor biopsies and matched normal specimens was profiled by the Quantidex™ NGS TP53 Assay (Asuragen, Inc.) and library analysis was performed using the Quantidex™ Reporter. TP53 mutation status was independently assessed by the AmpliSeq™ Cancer Hotspot Panel (Thermo Fisher Scientific). Whole transcriptome RNA-Seq was performed on isolated total RNA material. Gene and isoform expression quantitation as well as SNV and indel calling was performed on the RNA-Seq libraries. Results: TP53 mutation status for Quantidex TP53 and AmpliSeq assays was found to be concordant for regions of TP53 covered by both assays. The Quantidex TP53 Assay has more complete coverage of COSMIC mutations, 99% compared to 68% for AmpliSeq. Many TP53 positives were detected by the Quantidex Assay but negative by AmpliSeq due to coverage differences. The remaining discordant calls in commonly covered regions were assessed with matched RNA-Seq data. The comparison with RNA-Seq, led to the observation of specific cases of allele specific preferential expression of TP53 gain of function mutations. RNA-Seq expression profiles were also evaluated leading to the identification of gene signatures that associate with different TP53 mutation classes. Conclusions: TP53 profiling through orthogonal DNA-Seq assays and matched RNA-Seq has enabled the identification of a set of high confidence associations between TP53 mutations and RNA expression signatures in ovarian cancer. These results point to a path for clinical assays in which DNA mutations and pathway signatures are integrated in support of diagnostic and precision medicine applications. Citation Format: Brian C. Haynes, Diane Ilsley, Marie Fahey, Gary J. Latham, Elizabeth B. Somers, Daniel J. O9Shannessy. Characterization of TP53 mutations by DNA and RNA sequencing of platin-resistant ovarian cancer FFPE biopsies. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C204.


Platelet distribution width (PDW) and mean platelet volume are markers of platelet activation and have prognostic value in coronary heart diseases, as well as in cancers of solid organs. In this study, we evaluated the possibility of using PDW to predict chronic myeloproliferative neoplasms by comparing platelet indices obtained by automated analyzers in chronic myeloproliferative neoplasms with those in control specimens. We found that PDW greater than 66.4% has specificity of 99% and likelihood ratio of 19.5 for predicting chronic myeloproliferative neoplasms. Also, the area under curve (AUC) for platelet distribution width is 0.68.


The growth curves of aortic smooth muscle cells (SMCs) from spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar-Kyoto (WKY) rats, and genetically hypertensive (GH) rats and their normotensive outbred controls (N) were compared. The proportion of cells in the various phases of the cell cycle was measured by flow cytometry. SHR cells showed significantly shorter doubling time than WKY rat cells, but doubling times for GH and N rats did not differ and were nearly the same as for SHRs. SHRs showed significantly greater proportion of S-phase (DNA-synthesizing) cells compared to WKY rat cells in the exponential growth phase. No significant difference was observed between GH and N rats in the proportion of cells in other phases of the cell cycle. GH and N rat cells stopped dividing in fetal calf serum (FCS)-free Dulbecco's Modified Eagle Medium (DMEM), whereas SHR and WKY rat cells continued to progress through the cell cycle in serum-free DMEM. The responses of FCS-deprived-arrested cells to the addition of FCS were similar in GH and N rats. SHRs showed a prolonged increase in S-phase cells in response to FCS compared to WKY rat cells, but maximum effects were similar. Enhanced cell proliferation in SHRs is not present in the other hypertensive strain of rats and is not explained by a simple hyperresponse to FCS.


In the current study, Mahalanobis distance is used to compare the differences between two groups of university students' levels of self-efficacy, depression, anxiety, and stress. Differences between student groups for all dependent variables assessed at once aren't taken into account. Mahalanobis distance is an effective metric for determining a group of variables' dynamical character. For this study, three distinct dichotomous groupings of students are taken into account. Five dependent variables-general self-efficacy, specific self-efficacy, depression, anxiety, and stress-are compared using Mahalanobis Distance to see how dynamically they differ. It is discovered that the dynamical nature of five dependent variables for various sets of independent variables is not significantly different.

Keywords: General self-efficacy, Specific self-efficacy, Depression, Anxiety, Stress, Mahalanobis distance, University students.


Soil physical structure causes differential accessibility of soil organic carbon (SOC) to decomposer organisms and is an important determinant of SOC storage and turnover. Techniques for physical fractionation of soil organic matter in conjunction with isotopic analyses (dC, dN) of those soil fractions have been used previously to (a) determine where organic C is stored relative to aggregate structure, (b) identify sources of SOC, (c) quantify turnover rates of SOC in specific soil fractions, and (d) evaluate organic matter quality. We used these two complementary approaches to characterize soil C storage and dynamics in the Rio Grande Plains of southern Texas where C3 trees/shrubs (d C 1⁄4 27%) have largely replaced C4 grasslands (dC 1⁄4 14%) over the past 100–200 years. Using a chronosequence approach, soils were collected from remnant grasslands (Time 0) and from woody plant stands ranging in age from 10 to 130 years. We separated soil organic matter into specific size/density fractions and determined their C and N concentrations and natural dC and dN values. Mean residence times (MRTs) of soil fractions were calculated based on changes in their dC with time after woody encroachment. The shortest MRTs (average 1⁄4 30 years) were associated with all particulate organic matter (POM) fractions not protected within aggregates. Fine POM (53–250mm) within macroand microaggregates was relatively more protected from decay, with an average MRT of 60 years. All silt+clay fractions had the longest MRTs (average 1⁄4 360 years) regardless of whether they were found inside or outside of aggregate structure. dN values of soil physical fractions were positively correlated with MRTs of the same fractions, suggesting that higher dN values reflect an increased degree of humification. Increased soil C and N pools in wooded areas were due to both the retention of older C4-derived organic matter by protection within microaggregates and association with silt+clay, and the accumulation of new C3-derived organic matter in macroaggregates and POM fractions. r 2006 Elsevier Ltd. All rights reserved.


The design studio is an important part of design and architectural education, because of the unique approach of pedagogy used (Dutton, 1987, Salama, 1995, 2012). This research uses this space to examine the physical characteristics and properties of the design studio as a space, considering the ways it influences the behaviours and emotions of its users towards learning and collaborating with one another. Starting from the Sheffield School of Architecture, where the focus towards engaged and reflective learning. Trying to answer the research question 'How do the physical characteristics of the Design Studio influence certain behaviours of the studio user, relevant to collaborative learning?. Ultimately, attention is directed towards looking at their experience, which is created with the influence of the space, and the curriculum of architectural education, with both referred to as the 'design studio' (Crowther, 2013).
This research has 'empowered' users of the design studio (Literat, 2013), notably 'students' of four different universities in the context of the United Kingdom, through creating a hybrid research methodology that revolves around capturing their experience in relation to the physical space of the design studio. Under the umbrella of case study, using ethnography and focus groups, which were consisting of 'Student Designer Engagement Map', a method created based on a service design tool (Stickdorn and Schneider, 2011) to capture the current and aspired experience. These have then been analysed and interpreted through different lenses, i.e. the interior designer, tutor and the researcher.
The findings of the research were themed around spatial features in terms of social aspects, environmental control aspects and in terms of design organisation and furniture. The findings were related to the emotions experienced in the design studio through the project phases and stages. The hybrid methodology used and the methods have helped in creating a framework of propositional guidelines of design considerations, which may be beneficial for the stakeholders of the learning design studio and beyond.


The binding of thyroid hormone to the thyroid hormone receptor (TR) mediates important physiological effects. However, the transcriptional effects of TR mediated by the thyroid response element (TRE) cannot explain many actions of thyroid hormone. We postulate that TR can initiate rapid, non-TRE-mediated effects in the cardiovascular system through cross-coupling to the phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase Akt pathway. In vascular endothelial cells, the predominant TR isoform is TRα1. Treatment of endothelial cells with l-3,5,3′-triiodothyronine (T3) increased the association of TRα1 with the p85α subunit of PI3-kinase, leading to the phosphorylation and activation of Akt and endothelial nitric oxide synthase (eNOS). The activation of Akt and eNOS by T3 was abolished by the PI3-kinase inhibitors, LY294002 and wortmannin, but not by the transcriptional inhibitor, actinomycin D. To determine the physiological relevance of this PI3-kinase/Akt pathway, we administered T3 to mice undergoing transient focal cerebral ischemia. Compared with vehicle, a single bolus infusion of T3 rapidly increased Akt activity in the brain, decreased mean blood pressure, reduced cerebral infarct volume, and improved neurological deficit score. These neuroprotective effects of T3 were greatly attenuated or absent in eNOS−/− and TRα1−/−β−/− mice and were completely abolished in WT mice pretreated with LY294002 or a T3 antagonist, NH-3. These findings indicate that the activation of PI3-kinase/Akt pathways can mediate some of the rapid, non-TRE effects of TR and suggest that the activation of Akt and eNOS contributes to some of the acute vasodilatory and neuroprotective effects of thyroid hormone.


We study excitonic effects in two-dimensional massless Dirac fermions with Coulomb interactions by solving the ladder approximation to the Bethe-Salpeter equation. It is found that the general four-leg vertex has a power-law behavior with the exponent going from real to complex as the coupling constant is increased. This change of behavior is manifested in the antisymmetric response, which displays power-law behavior at small wave vectors reminiscent of a critical state, and a change in this power law from real to complex that is accompanied by poles in the response function for finite-size systems, suggesting a phase transition for strong enough interactions. The density-density response is also calculated, for which no critical behavior is found. We demonstrate that exciton correlations enhance the cusp in the irreducible polarizability at $2{k}_{F}$, leading to a strong increase in the amplitude of Friedel oscillations around a charged impurity.


Physical pain represents a common feature of Bondage and Discipline/Dominance and Submission/Sadism and Machochism (BDSM) activity. This article explores the literature accounting for how painful stimuli may be experienced as pleasurable among practitioners of BDSM, and contrasting this with how it is experienced as painful among non-BDSM individuals. We reviewed the available literature on pain and on BDSM, and used the findings to postulate a theory accounting for how painful stimuli are experienced as pleasurable. Our theory was then checked with BDSM practitioners. The emotional, physiological, and psychological elements of pain interact to facilitate the experience of pain as pleasure in BDSM. A multitude of interconnected factors was theorized to alter the experience of BDSM pain, including: neural networks, neurotransmitters, endogenous opioids and endocannabinoids, visual stimuli, environmental context, emotional state, volition and control, interpersonal connection, sexual arousal, and memories. The experience of pain in this context can bring about altered states of consciousness that may be similar to what occurs during mindfulness meditation. Through understanding the mechanisms by which pain may be experienced as pleasure, the role of pain in BDSM is demystified and, it is hoped, destigmatized.


Perhaps the most common dermal effect of quinin, when administered internally, is a form of hives or urticaria in which the surface is fairly covered with irregular shaped reddish colored blotches, varying in size from that of a dime to the palm of the hand. The skin is slightly elevated, has a hard, tense feel to the touch; there is usually intolerable itching and burning; sometimes the skin is so sensitive that even the slightest touch causes severe pain and feels as if a raw surface had been touched. In other cases the eruption is in the form of a rash, similar to that seen in scarlet fever. Often there is a uniform flush of the surface of the skin as in an erythema. Quite frequently a herpetic eruption follows the administration of quinin, which may be located on the lips, ear, cheek or prepuce. I have a lady patient


Type II topoisomerases modulate chromosome supercoiling, condensation, and catenation by moving one double-stranded DNA segment through a transient break in a second duplex. How DNA strands are chosen and selectively passed to yield appropriate topological outcomes – e.g., decatenation vs. catenation – is poorly understood. Here we show that at physiological enzyme concentrations, eukaryotic type IIA topoisomerases (topo IIs) readily coalesce into condensed bodies. DNA stimulates condensation and fluidizes these assemblies to impart liquid-like behavior. Condensation induces both budding yeast and human topo IIs to switch from DNA unlinking to active DNA catenation, and depends on an unstructured C-terminal region, the loss of which leads to high levels of knotting and reduced catenation. Our findings establish that local protein concentration and phase separation can regulate how topo II creates or dissolves DNA links, behaviors that can account for the varied roles of the enzyme in supporting transcription, replication, and chromosome compaction.


A Lattice Boltzmann Model (LBM) with the Poisson-Boltzmann equation for charge distribution is presented for the simulation of electroosmotic transport in straight rectangular micro- and nanochannels. Effects of the channel height, electrolyte concentration, surface potential, electric double layer thickness and externally applied electric field on the velocity profile of 50 to 800 nm channels were studied by means of a LBM. Our results are in excellent agreement with the corresponding analytical solution and the Lattice Boltzmann Model can be used to simulate electrokinetic transport phenomena in microchannels in the presence of an externally applied electric field.


We demonstrate a large area time domain terahertz (THz) imaging system capable of scanning 1 meter square area in less than 20-100 minutes for several security applications. The detection of concealed explosives; metallic and non-metallic weapons (such as ceramic, plastic or composite guns and knives); and flammables in luggage, packages and personnel has been demonstrated. Transmission mode images of luggage containing threat items are discussed. Reflection mode images of luggage and personnel are discussed. Time domain THz images can be analyzed for 3 dimensional and volumetric information. Time domain THz images have advantages over coherent narrow band imaging methods, with freedom from standing wave artifacts and with greater ability to discard irrelevant or intervening reflections through time discrimination.


During the coronavirus disease 2019 (COVID-19) pandemic, a novel multisystem inflammatory syndrome in children (MIS-C) has been reported worldwide since the first cases were reported in Europe in April 2020. MIS-C is temporally associated with severe acute respiratory syndrome coronavirus 2 infection and shows Kawasaki disease (KD)-like features. The epidemiological and clinical characteristics in COVID-19, KD, and MIS-C differ, but severe cases of each disease share similar clinical and laboratory findings such as a protracted clinical course, multiorgan involvement, and similar activated biomarkers. These findings suggest that a common control system of the host may act against severe disease insult. To solve the enigmas, we proposed the protein-homeostasis-system hypothesis in that every disease involves etiological substances and the host's immune system controls them by their size and biochemical properties. Also, it is proposed that the etiological agents of KD and MIS-C might be certain strains in the microbiota of human species and etiological substances in severe COVID-19, KD, and MIS-C originate from pathogen-infected cells. Since disease severity depends on the amounts of inflammation-inducing substances and corresponding immune activation in the early stage of the disease, an early proper dose of corticosteroids and/or intravenous immunoglobulin (IVIG) may help reduce morbidity and possibly mortality among patients with these diseases. Corticosteroids are low cost and an analogue of host-origin cortisol among immune modulators. This study's findings will help clinicians treating severe COVID-19, KD, and MIS-C, especially in developing countries, where IVIG and biologics supplies are insufficient.


The phenomenon of study analysis is limited to the spirit of service and applies the values nurses in a clinical service. Objective: is to identify the level of spirit service and ethical values in the participating nurses. Methodology: Its was a descriptive study observational and cross in a institution of second level care with 340 nurses assigned, of which 100 answered a self-applied form (emedic – 1 with a Crombach of 0,915) of 26 items, distributed at the beginning of the shift and collected through the floor managers at the end of the journey. The information is analyzed in relative frequencies. The hypothesis were: Spirit of service level in the study will qualify as high and means according to the scale emedic-1; the ethical values inherent nursing care such as humility , prudence and discretion will be at level low in the scale emedic-1 Results: The ethical values of caring identified in descending order are: caution, honesty, reliability, gentleness, discretion, diligence, humility and truth in clinical notes. The relevant indicators of the spirit of service are: call the patient by name, to avoid the cold and indifferent treatment, performance of procedures under a scientific and ethical principles, and good humor. Three indicator of the poor spirit of service are flexibility to the demands of the patient, patient neglect by overwork, and difficulty to offer a "plus" service. Conclusions: one important element is the related with the number of experts, who where in in this investigation. More than the third part of the nurses are clinic experts, the indicators of the spiritual service, which characterized the nurses is expressed in different ways.One attribute is definitely the best qualified to address the patient by name to avoid indifferent treatment although it is desirable that these two attributes will "always" accompanied by a good mood to perform the procedures.


Web and application servers nowadays often provide authorized users access to large amounts of sensitive data and services. These data and services need to be protected against unauthorized access. Thus, a lot of effort has been put into securing remote data access and network communication. However, attackers may get direct access to the data stored on the physical media, e.g., though theft or simply because of careless handling of disposed storage and backup media. In this paper, we describe a mechanism based on encrypted storage of documents and services on a server that enables transparent access to the data and services on the server while protecting the persistent data through encryption. In our approach, this data cannot be decrypted outside the context of a client connection and is thus worthless for anyone getting hold of the physical media.


Early diagnosis of Alzheimer's disease (AD) is an important task that facilitates the development of treatment and prevention strategies, and may potentially improve patient outcomes. Neuroimaging has shown great promise, including the amyloid-PET, which measures the accumulation of amyloid plaques in the brain—a hallmark of AD. It is desirable to train end-to-end deep learning models to predict the progression of AD for individuals at early stages based on 3D amyloid-PET. However, commonly used models are trained in a fully supervised learning manner, and they are inevitably biased toward the given label information. To this end, we propose a selfsupervised contrastive learning method to accurately predict the conversion to AD for individuals with mild cognitive impairment (MCI) with 3D amyloid-PET. The proposed method, SMoCo, uses both labeled and unlabeled data to capture general semantic representations underlying the images. As the downstream task is given as classification of converters vs. non-converters, unlike the general self-supervised learning problem that aims to generate task-agnostic representations, SMoCo additionally utilizes the label information in the pre-training. To demonstrate the performance of our method, we conducted experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. The results confirmed that the proposed method is capable of providing appropriate data representations, resulting in accurate classification. SMoCo showed the best classification performance over the existing methods, with AUROC = 85.17%, accuracy = 81.09%, sensitivity = 77.39%, and specificity = 82.17%. While SSL has demonstrated great success in other application domains of computer vision, this study provided the initial investigation of using a proposed self-supervised contrastive learning model, SMoCo, to effectively predict MCI conversion to AD based on 3D amyloid-PET.


Standard 10 of the Common Core State Standards attends to students' capacity with complex text. This standard distinguishes the Common Core State Standards from previous standards documents. This article describes a process—the Text Complexity Multi-Index (TCMI)—that supports teachers in studying texts to support their students in increasing capacity with complex text. The TCMI addresses the three prongs of the text complexity triad identified by the CCSS: quantitative, qualitative, and reader-task. As teachers apply steps of the TCMI process, they become increasingly knowledgeable about the features of texts that can create challenges for students and those that provide the content of lessons that support students in reading increasingly more complex texts across their school careers.


URING the last ten years it has been necessary to add to the traditional list of constituents of refuse a new item-plastics. Currently accounting for only one per cent of total weight, it is still at the bottom of the list, but its rapid growth rate and low density suggest that by 1980 it may account for as much as ten per cent by volume of all domestic refuse. It takes many forms: packaging film, expendable containers, lightweight foam, and consumer products; each with a different chemical structure. Most of Britain's refuse is disposed of by controlled tipping, and plastics are exacerbating the problem of maintaining visual amenity at tips because the lighter elements, especially thin sheets, are blown away during vehicle unloading. Plastic containers cause voids in the ground structure of the finished tip, increase the space required, and extend the time to complete consolidation. How convenient it would be if plastics were to decompose like paper, rags, and vegetable matter! t


During the last five years systematic explorations of the Natural History Museum of Crete have added more than 20 Pleistocene fossil localities ar ound Crete to the catalogue of the over 70 already known on the Island. The new localities are distributed in all four prefectures of Crete. The most important of these is the newly discovered site of Koutalas at Cape Drapano in Western Crete. The fossil remains are found in two levels a nd in red cemented clays of a collapsed cave. In the upper level a rich assemblage of micromammal, b ird and large mammal remains has been discovered. The large mammals consist of dwarf hipp opotamus (Hippopotamus creutzburgi) and elephants (Elephas sp.). A partly articulated skele ton (vertebral column, mandible and few long bones) of a dwarf hippo has been found next to a de ciduous molar of an elephantid, indicating that the two taxa probably coexisted. The micromammal re mains belong to the giant Cretan mouse Kritimys catreus. Therefore, the age of the assembl age is dated to the Kritimys catreus zone and thus to the late Middle Pleistocene. In the lower lscattered remains of deers, birds and micromammals have been identified, and their age is most likely younger than that of the upper level.


Turkey occupies eighth place in the world for cave tourism. In recent years, the development of the cave tourism industry throughout the country and the emergence of its positive and negative impacts have attracted the interest of rural development experts, local managers and scholars. Most research is related to scientific studies in caverns, but there has been insufficient study of the profiles of visitors, expenditure patterns and problems experienced by cave tourism destinations. The main aim of this study is to analyse the determinants of the expenditure of same-day visitors on cave tourism, the socio-economic characteristics of the tourists and their attitudes towards the Ballica Cave as a tourist destination. Data were collected from 598 visitors via a questionnaire survey. The double log function was used to determine visitor expenditure on cave tourism. The geographical position of the cave and characteristics of the visitors were taken into consideration when specifying the model. According to the findings, the effect of household income on visitor expenditure was positive but not significant. Distance, age, level of education and gender were important determinants of expenditure. In addition, the majority of respondents thought that the advertising of the Ballica Cave was inadequate. Relatives, friends and neighbours were the main information sources for visitors to the cave.


We performed a prospective study to determine the prevalence of cholelithiasis in patients with abdominal aortic aneurysm. Over an 18-month period, the gallbladder and the abdominal aorta were evaluated routinely in all consecutive patients referred to us for sonography of the abdomen and retroperitoneum. The patients were divided into two groups: those with an abdominal aortic aneurysm (aorta greater than 3 cm in transverse diameter) (n = 96) and those whose aorta measured less than 3 cm in transverse diameter (n = 538), who served as control subjects. Cholelithiasis was found in 50% of patients with and 26% of patients without aneurysm (p less than .0001). A stepwise logistic regression analysis found age alone to be predictive of cholelithiasis (p = .030). However, age was not predictive of cholelithiasis when included with abdominal aortic aneurysm in a multivariate model. Diabetes mellitus and gender were not predictive of cholelithiasis. We found cholelithiasis in approximately half of the patients who had abdominal aortic aneurysms. This is almost double the prevalence in the general elderly population. A pathophysiologic explanation for this observation remains to be found.


This article is a continuation of the series focusing on managing IT change in an organization. As businesses move from functional logic to integrated business processes, this series of articles has discussed the way in which different functions relate to new processes. Also, we have reviewed how other factors, such as tools and programs, used to organize and manage the enterprise, have a pronounced impact on performance. Further, this transition must be managed as part of longer-term continuous improvement programs for the overall enterprise. In our previous article, we discussed the role of business leadership in evaluating and defining IT strategy necessary to support these major and disruptive changes. One additional aspect of IT strategy that bears discussion is IT function staffing and where the work will be completed. When decisions are based on projected cost calculations, they invariably do not include an end-to-end understanding of knowledge transfer. This is a complex task moving from problem identification to whatever development organization will do the work and testing, and back. This article starts with a definition of knowledge transfer among organizational components and then discusses the role that each design component may play in efficiently and accurately completing the work. © 2017 Wiley Periodicals, Inc.


This book and the accompanying software (PC Diskette) is a toolbox for performing a set of numerical simulations on simple quantum mechanical problems. It is one in a series of similar books (CUPS) covering different fields in physics from classical mechanics to nuclear and particle physics. Each chapter of the book is written by a different author and deals with a different physical problem. The choice of problems is standard, e.g. bound state and scattering problems in one and three dimensions, quantum mechanical time development; the exceptions are, a study of identical particles and electron states in a one dimensional lattice, an example from solid state physics. Although the chapters are self-contained and can be studied independently (at the expense of some minor duplication of material), care was taken with a uniform style of presentation and similar format in numerical simulations. As a result, it is easy to proceed in the study of the different problems having understood the technical possibilities of one simulation. Each chapter starts with a section presenting the basic theoretical concepts to be studied using the numerical simulation. It is followed by a section with a short description of the numerical technique used and an extensive series of suggestions for problems and quantities to experiment with, using the computer codes provided. A final section describes in detail how to run the computer programs. This book is not, and is not intended to be, a textbook for learning quantum mechanics nor a textbook of numerical analysis. Nevertheless, I find the theoretical presentation clear and straightforward enough for its purpose. The extensive and up to date list of references to books and research articles at the end of each chapter is also very helpful. Technically, I found the software easy to install and, after some initial testing, easy to run. The produced plots are clear and the use of units of atomic dimension gives a touch of reality to the simulations. In contrast to other similar books, this is not a `picture' book of quantum mechanics where results of numerical simulations are illustrated; here the reader is given the necessary means to play and discover for himself the properties of quantum mechanical systems. I believe that this book, used by teachers for demonstrations and students for independent study, provides a versatile tool for numerical experimentation in quantum mechanics.


Two-dimensional (2D) photonic crystals composed of polymer pillar arrays were fabricated by a nanoimprinting process using ordered anodic porous alumina molds. The obtained 2D polymer photonic crystals exhibited a clear stop band in the visible wavelength region, which originated from the periodic pillar arrays. The position of the stop band could be controlled by changing the geometrical structure of the anodic porous alumina mold. The process allows the high throughput production of 2D photonic crystals, which are required for the preparation of various types of functional optical devices.


Abstract Relational contexts are a central issue in most people's lives, and people usually rely on the support of others in everyday circumstances. Social support, as a relational context, could have a positive influence on personal adjustment, and is particularly relevant in the psychological well-being of HIV patients. Guided by the Convoy Model of social networks, in a sample of 31 HIV-positive pregnant women we try to assess the role of social support and social network in the adjustment to pregnancy. Profile analysis suggests a greater importance of social support provided by the partner and both parents, especially the support provided by the mother. At the same time, it seems to highlight the buffering hypothesis of social support, which could be understood as a protection factor in the adjustment of HIV-infected women' to pregnancy.


Lymph nodes were withdrawn from twenty foetuses and eighteen newborns. Paraffin embedded tissues were stained by current histochemical methods and immunohistochemically processed with a panel of antibodies against dendritic reticulum cells (DRC) (CD21, CD35), endothelial cells (QBEnd/10-CD34, CD31, Factor VIII RAg), B lymphoid cells (L26, MB2), T lymphoid cells (UCHL1, DF-T1, OPD4), monocytic cells (PGM1, KP1) and interdigitating dendritic cells (S100 protein, PGM1). The immunohistochemistry was focused on determining the initial appearance of DRC whose origin is still debated. They are currently considered to be transformed mesenchymal cells. This study shows that DRC make their appearance in the superficial or subcutaneous lymph nodes just at the beginning of extrauterine life whereas they are identifiable in the mesenteric lymph-nodes already during the foetal life. They acting as an enhancing microenvironment, appear to be related to B lymphocyte expansion. Their derivation from endothelial cells rather than other mesenchymal cells seems more probable.


Metallic materials have gained much attention recently from the areas of medical devices and orthopaedics. Artificial organs, dental implants, prostheses and implants that replace damaged or malfunctioning parts in the body are, or contain, metal components. Our ageing society poses an increased demand to provide devices and implants that can demonstrate better performance than those presented by traditional solutions. Matching the mechanical properties (i.e. stiffness and strength) of the device to those of the host tissue is a major challenge for the design and manufacture of engineered metal materials for biomedical applications. Failure in doing so provokes implant loosening, patient discomfort and repeated surgeries. Therefore, tailoring physical properties and biocompatibility of those materials is the main final aim of this research programme.
This PhD study has focused on the tailoring of the mechanical properties of titanium-based materials and titanium-based alloys. Titanium inertness and the selection of biocompatible alloying elements were set as the baseline. Two approaches were employed to decrease stiffness (i.e. Young s modulus): one, by introducing porosity in a titanium matrix and therefore, reduce its Young s modulus, and two, by designing and manufacturing beta-titanium-based alloys with a reduced Young s modulus. Titanium scaffolds were manufactured using powder metallurgy with space holder technique and a sintering process. Different space holder sizes were used in four different categories to study the effect of pore size and porosity on the mechanical properties of the porosity engineered Ti scaffolds. Ti-based alloys were manufactured using manufacturing techniques such as sintering and arc-melting. The effect of different fabrication processes and the addition of beta-stabilising elements were studied and investigated.
The obtained results of mechanical properties for pore size and porosity were within the values that match bone properties. This means these materials are suitable for biomedical application and the beta-Ti alloys results show that the mechanical properties can be decreased via tailoring the crystal structures. The characterisation of the Ti-based alloys helps to develop this material for its use in biomedical application.


Reports of profound changes in species assemblages brought about by the influence of strongly interacting species are increasingly common. Where these strong interactors are sensitive to anthropogenic habitat changes, relatively small alterations in the environment can result in large and pervasive shifts in assemblages. We review the evidence for widespread assemblage‐level phase shifts across eastern Australia, triggered partly by anthropogenic habitat alteration and mediated by a native, despotic bird: the noisy miner Manorina melanocephala.


Zein is a hydrophobic plant protein characterized by a good biodegradability and insoluble characteristics making it a good candidate for the development of biopolymeric nanoparticles for drug delivery. In this study, three types of zein nanocarriers were developed for targeted delivery of poorly soluble anti-cancer drugs. First, zein nanospheres were successfully prepared via phase separation technique for co-delivery of exemestane and luteolin. Second, zein nanocapsules were successfully developed using spontaneous emulsification technique for co-delivery of exemestane and resveratrol. The developed drug-loaded zein nanospheres and nanocapsules demonstrated a suitable particle size (150-250 nm) and a negative zeta potential (above -30 mV) exhibiting a controlled drug release behavior. The surface of zein nanocarriers was successfully decorated with lactoferrin as a tumor-targeting ligand via electrostatic interaction. In the third part of this study, amphiphiliczein-lactoferrin co-polymeric micelles for co-delivery of rapamycin and wogonin were successfully developed. The chemical conjugation via carbodiimide-coupling technique was evidenced by NMR, IR and fluorescence spectroscopy while the core-shell structure of the micelles in aqueous solution was demonstrated by TEM. The drug-loaded self-assembled nanocarriers exhibited a nanometric size (100-250 nm) and a positive zeta potential (around +30 mV) in addition to high drug loading and a sustained release profile. The developed zein nanocarriers showed superior cytotoxicity and cellular uptake against MCF-7 breast cancer cells and powerful in vivo anti-tumor efficacy in breast cancer rat model compared to free drugs. Thereby, zein nanocarriers could evoke a new effective tumor-targeted delivery system to breast cancer by passive and active targeting. A nanocapsule is a nanoscale shell produced using a nontoxic polymer. They are vesicular frameworks made of a polymeric layer which epitomizes an inward fluid center at the nanoscale. Nanocapsules have numerous utilizations, including promising clinical applications for sedate conveyance, food improvement, nutraceuticals, and for self-recuperating materials. The advantages of embodiment strategies are for security of these substances to ensure in the antagonistic condition, for controlled discharge, and for accuracy targeting. Nanocapsules can possibly be utilized as MRI-guided nanorobots or nanobots, in spite of the fact that difficulties remain.The exemplification strategy relies upon the prerequisites for some random medication or substance. These procedures rely upon the physiochemical properties of the center material, the divider material, and the required size. The most widely recognized approaches to create nanocapsules are nanoprecipitation, emulsion-dispersion, and dissolvable dissipation. In the nanoprecipitation strategy, additionally named dissolvable uprooting technique, nanocapsules are framed by making a colloidal suspension between two separate stages. The natural stage comprises of an answer and a blend of natural solvents. The watery stage comprises of a blend of non-solvents that frames a surface film. The natural stage is gradually infused in the watery stage which at that point is unsettled to shape the colloidal suspension. When the colloidal suspension is framed it will be unsettled until nanocapsules start to shape. The size and state of the nanocapsule rely upon the pace of infusion alongside the pace of agitation. Another basic method to get ready nanocapsules is the emulsion dispersion strategy. This technique comprises of three stages: natural, fluid, and weakening stage. In this technique the natural stage is added to the watery stage under states of high disturbance which structure an emulsion. During this procedure water is added to the emulsion which makes the dissolvable diffuse. The aftereffect of this emulsion-dissemination is nanocapsule formation. Dissolvable vanishing is another compelling strategy to get ready nanocapsules. In this procedure, single or twofold emulsions are shaped from solvents and are utilized to plan a nanoparticle suspension. Fast homogenization or ultrasonication is utilized to frame little molecule size in the nanoparticle suspension. When the suspension is steady, the solvents are dissipated utilizing either constant attractive blending at room temperature, or by lessening the encompassing pressure.The table underneath shows how nanocapsules display various qualities dependent on the strategy by which they were readied. Nanocapsule types change by size, tranquilize fixation, and dynamic substance discharge time.Close infrared light: Drug discharge is activated from heat. The infrared innovation can be consumed somewhere down in the body, go to warm. The warmth delicate material, especially a polymer shell that swells after warming, breakdown. The activity of emptying is the thing that discharges the drug. Attractive fields: Magnetic bars of millimeter-scale are installed in poly(vinyl liquor). The attractive field inside the bars is rotated, which brings about the difference in shape and extreme breakdown of the nanocapsules. The adjustment in the structure at that point triggers the medication release. Ultrasound: Another choice of medication discharge is through ultrasound, which is a "longitudinal weight wave". The ultrasound can either be low-recurrence, or LFUS, (somewhere in the range of ~20 and ~100 kHz) or high-recurrence, HFUS, (>1 MHz). Transdermal conveyance (sonophoresis) is upgraded through LFUS, which at that point further permits the medication to be discharged. Since the flood of HFUS is higher, accomplishment of medication conveyance has been shown through the type of air pockets. The air pockets with in the container are framed and crumpled because of the higher temperatures of the wave. Some different ways incorporate oral, which is the most dynamic, nasal, transdermal, and through the lung. Oral is the most widely recognized, and the most testing. Requests for steady discharge continue, despite the fact that advancements are being made for medications to bioadhere to the intestinal tract. Bioadhesion is additionally being considered for nasal conveyance, to drag out the life of the medication inside the nose. Medications can likewise be moved through the skin (transdermal). Inhalers are additionally of enthusiasm, as, asthma drugs comprise of macromolecules. Right now, the inward breath frameworks are bothersome to patients, and it is trusted that there will be progresses in this conveyance framework at some time.


This book is a regional history of Lesbos and the Troad from the seventh century BC to the first century AD which examines the extent to which this geographical region became politically, economically, and culturally integrated over this extended timeframe. The case studies in each chapter examine the various human and geographical factors which promoted regional integration, but also consider the political and identity-based considerations which limited integration and curtailed co-operation in particular areas. It is argued that this produced a situation in which an economically well-integrated region nevertheless remained politically fragmented and was only capable of unified action at moments of crisis. The book is split into two halves, with the first examining both the human and geographical factors which contributed to regional integration in the Troad and the politics of this process and the second examining the insular identity of Lesbos, the extent to which it was integrated into the mainland, and the consequences of this integration for the internal dynamic of the island. Cross-cutting these regional dynamics are the various imperial systems (Persian, Athenian, Macedonian, Attalid, Roman) which ruled this region and shaped its internal dynamics both through direct interventions in regional politics and through the pressures and incentives which these imperial systems created for local communities.


Is the Aboriginal Flag art? And, if it is, to what end does that claim serve? 'Art' is not a helpful noun, and certainly a risky one on which to base an argument. Yet, to fail to read the Aboriginal Flag as art – or, more precisely, to fail to read it as Indigenous activist art – is to fail to understand the Aboriginal Flag , and more broadly the role of culture in Indigenous activism, post European settlement. The Aboriginal Flag 's Indigenous and Western art epistemologies are instrumental in shaping its form and semantics. As Aboriginal art, the flag represents a continuum with traditional Aboriginal themes and aesthetic values. In a Western context, it is read as a flag, and it exists as a mass-produced object. In all its guises the Aboriginal Flag has melded itself into many aspects of popular imagination and become one of Australia's significant symbols. The contested history of the Aboriginal Flag – evident in the passion it evokes on both sides of Australia's race-based cultural divide – demonstrates that both white and black Australians understand the Aboriginal Flag to be a powerful political symbol. The Aboriginal Flag is therefore two things simultaneously: a work of art and an activist symbol. As a successful pairing, this alliance is rare because each entity or discipline has different values and agendas: activism seeks to bring about social change, art-making is concerned with the subject of art. To confuse matters further, as a work of social and political art the Aboriginal Flag achieves something very rare: it brings about social change. Understood in this way, the Aboriginal Flag has three conceptualising foundations: art, activism and social change. In its totality, the Aboriginal Flag represents evidence of a particular type of art – of which it is exemplary – that remains largely unrecognised as an artistic genre. In light of these factors, it is necessary to define the Aboriginal Flag as distinct from other social and political contemporary works of art that have emerged in recent decades. These art-based interpretations of the Aboriginal Flag constitute the architecture or, more precisely, the armature of this thesis. They give form and structure to the flag's histories and meanings that in their totality form a cohesive reading of the Aboriginal Flag that is whole and distinctly Indigenous.


What do we mean when we say we "know" something? What is this knowledge and how do we come by it? What exactly counts as an object of knowledge? And on what basis do we defend our claims to know against those - the sceptics - who deny that knowledge is possible or that our criteria for knowing can ever be satisfied? These questions and many others are addressed in this fascinating collection of essays by leading philosophers, who discuss the nature, meaning, and extent of human knowledge. Included are works by Robert Almeder, William P Alston, Robert P Amico, Roderick M Chisholm, Edmund L Gettier, Richard Feldman, Peter D Klein, Keith Lehrer, Kenneth G Lucey, John Pollock, and others. Several essays are original to this collection and break new ground on such issues as the Problem of the Criterion.


Botanical diversity of the South of Tai National Park, Cote d'Ivoire The Tai National Park (TNP) is one of the last vestiges of ≪ primary ≫ forest remained in West Africa. The northern part is almost well known but the southern one is not. To mitigate this lack, we conducted a study in the South of the TNP. To achieve the inventory, two methods were used: "walk set up" and the "plot set up". Nine hundred height plants species were recorded. They belonged to 550 genera and 116 families. The richest families were Rubiaceae, Euphorbiaceae and Caesalpiniaceae. Among all the species, 175 were endemic of West African forests, 11 endemic to Ivorian forests and 61 "sassandrian". The study showed that for tree species with dbh ≥10 cm Hymenostegia afzelii, Strombosia pustulata,  Diospyros sanza-minika, Funtumia africana, Calpocalyx brevibracteatus and representatives of Caesalpiniaceae, Euphorbiaceae and Ebenaceae families were the richest and had the highest values of IVI and FIV. Endemic, "sassandrian", rare and threatened species constitute the major characteristic of the TNP and confirm that it includes in the Guinean Forests of West Africa Hotspot .


This study was conducted to assess the efficacy of systemic chemotherapy in patients with brain metastasis from non-small cell lung cancer. Sixty-three consecutive patients who were diagnosed as having non-small cell lung cancer (NSCLC) with synchronous brain metastasis (BM) and had not been previously treated were included in this study. After cranial radiation therapy (RT), all patients in 'the chemotherapy arm' (CTX) were treated with platinum-based combination chemotherapy, and best supportive care was selected for patients in 'the no-chemotherapy arm' (no-CTX). Thirty-one of the 63 patients received systemic chemotherapy. The median age of all patients was 55 years. The performance status of all patients was ECOG grade 1-2. Twenty-two patients had a solitary brain metastasis, 37 patients had more than two masses, and 38 patients had extracranial metastatic lesions. In the CTX arm, a paclitaxel-based combination chemotherapy was administered in 38.7%, gemcitabine-based in 25.8%, and vinorelbine-based in 25.8% as the first-line chemotherapy. Seventeen patients were treated with a second-line chemotherapy, and paclitaxel plus gemcitabine was used in 8 patients. For the first-line and second-line chemotherapies, extracranial overall responses were 36 and 35%, the median response durations were 29.1 weeks (range: 9.1-58.1 weeks) and 30.4 weeks (range: 19.4-44.0 weeks), respectively. 'Progression of the extracranial lesion' (58.1%) was more frequent than an 'aggravation of neurologic status' (19.4%) for the pattern of treatment failure in the first-line chemotherapy. The causes of failure were identical in the second-line chemotherapy. The median survival of the CTX arm was longer than that of the no-CTX arm (58.1 vs. 19.0 weeks, p<0.001). Toxicity in the CTX arm was tolerable. The systemic chemotherapy showed an effectiveness to increase the survival of patients with BM from NSCLC, and extracranial progression was the main cause of chemotherapeutic failure, although consideration for non-randomized methods should be made in this study.


solely, the cervical sympathetic nerves. The author may subsequent chapters review the patho-physiology of find that nervous control of the circulation in the brain is human muscular dystrophy (Richterich), the clinical more widely accepted than he appears to expect, and it characteristics of myopathy in childhood (Demos), will be interesting to know whether his other views are cardiac involvement (Weber), histopathology (Mumenconfirmed as new methods for the study of brain flow thaler), electron microscopy (Molbert), drug treatment become available. (Beckmann), orthopaedic treatment (Taillard), and the J. SPALDING differential diagnosis of the 'floppy infant' syndrome (Zellweger). Five of the chapters are written in German, SPONGY DEGENERATION OF THE BRAIN IN INFANCY By three in French, and one in English. As a short review of L. van Bogaert and I. Bertrand. (Pp. 178; 36 figures. current knowledge, intended for paediatricians and 50s.) North Holland Publishing Company: Amstergeneral physicians, the volume succeeds in its aim, but dam. 1967. owing to the relative brevity and unevenness of the The recognition of this familial disease as a distinctive various chapters the book will be of comparatively little pathological entity dates from the paper given by van interest to British neurologists; to those with a particular Bogaert and Bertrand at the Paris Neurological Congress interest in diseases of muscle a number of isolated observain 1949. In retrospect, it is probable that Globus and tions in the chapters by Zellweger, Mumenthaler, and Strauss (1928) and Canavan (1931) had given earlier Molbert will be of value. The remaining chapters contain descriptions of the condition, but it is certainly unjustilittle that is new and even the reviews of recent literature fiable to retain the term 'Canavan's disease' in present-day are somewhat incomplete; at a time when the proceedings classifications. of many large meetings and symposia devoted to muscle This monograph contains a full account of the clinical disease in its many aspects are being published, the appeal and pathological features of the 26 examples of this of this book will be very limited. disease which have so far appeared in the literature and the authors' personal cases are set out in considerable NEW CONCEPTS IN PAIN AND ITS CLINICAL MANAGEMENT detail. Pathologists will be grateful for van Bogaert's Edited by E. Leong Way. (Pp. xiv + 224; 51 figures. account of many other rare encephalopathies of early life 64s.) Blackwell Scientific Publications: Oxford. 1967. which are to be considered in differential diagnosis and The title of this book is something of a misnomer, since the book will be a valuable source of reference both to it is not concerned with new concepts in pain so much as clinicians and neuropathologists. new applications of old concepts. The work represents R. M. NORMAN the proceedings of a symposium held in San Francisco in


Thalassemia is a genetic hematologic disease, characterized by a defect in hemoglobin chain synthesis. Because of safe transfusions and effective chelation therapy, survival of affected patients has significantly improved in the last few decades. However new complications are appearing. Among them are hepatocellular carcinoma and other forms of cancer, particularly hematologic malignancies. The present review focuses on the frequency of cancer in thalassemia patients and on possible predisposing factors.


Human activities markedly modify diversity patterns of plant communities and their response to environmental conditions, with subsequent consequences for ecosystem functions. We measured 11 key functional traits of 47 plant species and assessed both taxonomic and functional composition as well as above‐ground biomass (AGB) of plant communities from 127 plots in the Lake Dongting wetland. Using a generalized multilevel path model, we examined the cascading effects of hydrological gradients on plant diversity and ecosystem functions in two distinct habitat types (short grassland with a natural community dominated by Carex spp. and tall grassland with a managed artificial community dominated by Triarrhena lutarioriparia and Phragmites australis). We found significant differences in the response of plant diversity and AGB to hydrological gradients. Species richness, Shannon–Wiener diversity, multiple‐trait functional diversity measures (i.e., functional richness, functional dispersion & Rao's quadratic entropy) and community‐weighted mean (CWM) of shoot height were all significantly higher and functional divergence and CWM of tuber significantly lower in tall grassland. AGB was significantly higher in short grassland, largely driven by variations of functional diversity rather than of taxonomic diversity. Moreover, we found a significant cascading effect of elevation and soil moisture on AGB, directly or indirectly induced by changes in functional diversity in the short grassland, while only direct effects of elevation on AGB were observed in the tall grassland. Therefore, our study provides strong evidence that human‐induced changes in habitat types uncoupled the cascading effects of hydrological gradients on ecosystem functions mediated by either the taxonomic or the functional diversity.


Acetaminophen (AAP) is a commonly analgesic found in numerous non-prescription pharmaceuticals. High dose and
chronic ingestion of AAP caused renal toxicity. This study is designed to assess the possible nephroprotective role of
flaxseed oil (FSO) in male rats. Nephrotoxicity was induced in rats via ingested a single dose of AAP (3 g/kg). Five groups
of rats were used; Control, AAP, FSO (1.5 ml/kg) + AAP, FSO (3 ml/kg) + AAP, and FSO (4.5 ml/kg) + AAP. Rats were received
orally FSO for 30 days and at the 30th day received AAP 1 h before FSO. Serum renal function indices were determined.
Also, antioxidants, oxidative stress, and pro-inflammatory cytokines indices were measured in serum. Ingestion of FSO (3
and 4.5 ml/kg) prior to AAP intoxication significantly decreased AAP-induced nephrotoxicity as evidenced by significant
decrease in renal functions relative to the AAP group. Prevented the oxidative stress as evidenced by significant increases
in SOD and GSH levels, concurrent with a significant decline in MDA level. Besides, there were significant decreases
in IL-1α and TNF-α relative to the AAP group. FSO (3 and 4.5 ml/kg) preserved the renal parenchyma, glomerulus and
tubules histological features induced by AAP. FSO (4.5 ml/kg) was markedly the most effective dose relative to the two
other doses. In conclusion, FSO protects AAP-induced renal toxicity in a dose dependent manner via its potent antioxidant
and anti-inflammatory activities.


As online crowdsourcing has shown, people will support a proposed business or cause that moves them. For entrepreneurs, the ability to test a proposed product or service's uniqueness and appeal has never been better. EIX panelists Heidi Neck of Babson College, Kim Eddleston of Northeastern University and Dan Holland of Utah State University discuss how entrepreneurs can test the waters before they roll out their business ideas.


The development of new technological solutions in the field of daily consumed food products, which have a directed corrective impact on the nutritional status of the human body and an extended shelf life is an important and urgent task. One of the alternative solutions to the problem faced is the introduction of flour products (crackers, biscuits, bread), enriched with biologically active substances of plant origin into the daily ration. They are economically accessible to the general population and suitable for sale in a network format, due to significant shelf life. Experimental studies to assess the effect of introduced biologically active substances on the shelf life of flour products through the study of changes in the content and ratio of various forms of bound moisture were carried out in the work. The study of moisture state in flour products was carried out by the method of differential thermal analysis using a synchronous thermal analysis device using thermogravimetry, differential scanning calorimetry and non-isothermal kinetics. The objects of research were samples of flour products containing the composition of partially defatted wheat germ flour "Vitazar" and wheat bran, which were additionally added with seaweed powder, soy protein isolate, pea protein isolate, black cumin seed flour. Samples of flour products (biscuits) made according to traditional technology served as controls. A quantitative assessment of the ratio of moisture fractions with various bonds was carried out by the methods of thermogravimetry, differential scanning calorimetry and non-isothermal kinetics. The ranges of endothermic effects, indicating stepwise moisture removal, in accordance with the forms and energy of its connection with the experimental samples biopolymers were identified in the work. Comparison of thermal effects characteristics recorded in the process of thermolysis of flour products samples, allows us to state an increase in the chemically bound moisture share in the test samples, as compared with the control sample and, as a result, an increase in shelf life.


Detailing the kinetics of particle formation for pharmaceutically relevant solutions is challenging, especially when considering the combination of formulations, containers, and timescales of clinical importance. This paper describes a method for using commercial software Automate with a stream-selector valve capable of sampling container solutions from within an environmental chamber. The tool was built to monitor changes in particle size distributions via instrumental particle counters but can be adapted to other solution-based sensors. The tool and methodology were demonstrated to be highly effective for measuring dynamic changes in emulsion globule distributions as a function of storage and mixing conditions important for parenteral nutrition. Higher levels of agitation induced the fastest growth of large globules (≥5 μm) while the gentler conditions actually showed a decrease in the number of these large globules. The same methodology recorded calcium phosphate precipitation kinetics as a function of [Ca2+] and pH. This automated system is readily adaptable to a wide range of pharmaceutically relevant systems where the particle size is expected to vary with time. This instrumentation can dramatically reduce the time and resources needed to probe complex formulation issues while providing new insights for monitoring the kinetics as a function of key variables.


The flow of formation waters in the Upper Devonian-Lower Cretaceous sedimentary succession in the south-central part of the Alberta basin is controlled mainly by (1) outcrops of Devonian and Mississippian strata at high elevation in the south in Montana, and at low elevation at the Peace River in the north; (2) subcrops of Devonian to Jurassic strata at the sub-Cretaceous unconformity; and (3) deposition of Cretaceous sediments on pre-Cretaceous relief exposed for a long period of time. Weathering of Upper Devonian strata during this long period of subaerial exposure and the concurrent paleokarsting of the Grosmont Formation led to high permeability in these aquifers. As a result, the Grosmont aquifer and the Upper Devonian aquifer system that subcrop at the sub-Cretaceous unconformity form a drainage path in a northward regional-scale flow system in the southern and central parts of the Alberta basin. This long-range flow system is fed by meteoric recharge in the south, by updip flow of connate waters from deep Paleozoic aquifers that subcrop along the western flank of the main system, and by downdip meteoric recharge through Cretaceous strata along the eastern basin edge. A plume of relatively high salinity is formed in the Lower Mannville aquifer in the area where highly saline Devonian waters discharge at the sub-Cretaceous unconformity and mix with fresh water of meteoric origin. Hydrocarbons generated in Upper Devonian to Lower Cretaceous strata of the deep foreland basin migrated northeastward updip, driven by buoyancy and supported by a concurrent hydrodynamic drive. The great majority of the generated hydrocarbons reached the sub-Cretaceous unconformity, where they were trapped in complex stratigraphic traps in the Lower Mannville Formation. Downward flow of meteoric water along (Begin page 638) the eastern flank of the basin hydrodynamically enhanced the trapping and led to hydrocarbon biodegradation in place into heavy oils and oil sands in the Cold Lake and Athabasca areas.


Background More than 50% of all patients with colorectal cancer (CRC) develop liver metastases (CLM), a clinical condition characterized by poor prognosis and lack of reliable prognostic markers. Vδ1 cells are a subset of tissue-resident gamma delta (γδ) T lymphocytes endowed with a broad array of antitumor functions and showing a natural high tropism for the liver. However, little is known about their impact in the clinical outcomes of CLM. Methods We isolated human γδ T cells from peripheral blood (PB) and peritumoral (PT) tissue of 93 patients undergone surgical procedures to remove CLM. The phenotype of freshly purified γδ T cells was assessed by multiparametric flow cytometry, the transcriptional profiles by single cell RNA-sequencing, the functional annotations by Gene Ontology enrichment analyses and the clonotype by γδ T cell receptor (TCR)-sequencing. Results The microenvironment of CLM is characterized by a heterogeneous immune infiltrate comprising different subsets of γδ tumor-infiltrating lymphocytes (TILs) able to egress the liver and re-circulate in PB. Vδ1 T cells represent the largest population of γδ TILs within the PT compartment of CLM that is greatly enriched in Vδ1 T effector (TEF) cells expressing constitutive high levels of CD69. These Vδ1 CD69+ TILs express a distinct phenotype and transcriptional signature, show high antitumor potential and correlate with better patient clinical outcomes in terms of lower numbers of liver metastatic lesions and longer overall survival (OS). Moreover, intrahepatic CD69+ Vδ1 TILs can egress CLM tissue to re-circulate in PB, where they retain a phenotype, transcriptional signature and TCR clonal repertoires resembling their liver origin. Importantly, even the increased frequencies of the CD69+ terminally differentiated (TEMRA) Vδ1 cells in PB of patients with CLM significantly correlate with longer OS. The positive prognostic score of high frequencies of CD69+ TEMRA Vδ1 cells in PB is independent from the neoadjuvant chemotherapy and immunotherapy regimens administered to patients with CLM prior surgery. Conclusions The enrichment of tissue-resident CD69+ Vδ1 TEMRA cells re-circulating at high frequencies in PB of patients with CLM limits tumor progression and represents a new important clinical tool to either predict the natural history of CLM or develop alternative therapeutic protocols of cellular therapies.