: Phonecards have been collected as a hobby by Brazilian people with a peak in the number of collectors (around 300 thousand people) from 1994 to the beginning of the 2010s. The objective of this study was to report the revival of phonecard collection as a hobby in Brazil through estimating the number of collectors and other associated parameters from April to June 2021. The number of phonecard collectors was evaluated on Facebook groups for each Brazilian State and the Federal District (Brasília) on 16 April, 5 May and 5 June 2021. The number of phonecard collection groups on Facebook from other countries was also evaluated. The number of Brazilian groups was 44 and of members, 81,104 in the last assessment date on 5 June 2021, being the country with the highest number of collectors. In thirteen Brazilian States and the Federal District (Brasília), most of the groups (10) had been opened for around 10 years. Italy had the second highest number of phonecard collectors. The revival of phonecard collection as a hobby in Brazil is clear. This revival is suggested to be associated with the attractive images pictured on phonecards, financial condition of the collectors and locations where they live as well as an increase in the number of hours spent with recreational activities at home.


Nonvolatile and thermolabile antibiotics are investigated both by field desorption and by secondary ion mass spectrometry (SIMS). It has been successfully demonstrated that these two methods are complementary in obtaining informations about molecular weight and structure. Although FD is most widely used for the investigation of nonvolatile biologically active compounds, there are some compounds of which FD can not provide reliable information. SIMS is successfully applied to obtain structural information of these compounds. SIMS spectra frequently depend on the surface conditions of sample holder materials.


Crude palm oil (CPO) is one commodity that could be consumed and also as one alternative of non- fossil fuel: biodiesel. Since 2006, CPO commodity trade has its significant raise, followed by forward contract trade. The increasing of CPO price in 2006 is the lowest in historic analysis data period 2007-2008. Cyclic forecasting model is used following cycle pattern of twice-a-year, with a combination of Solver function in Ms. Excel that could minimize MSE as 161,02, Beta 0,0688 and intercept in -11,0396. Cyclic forecasting period is supposed to be used along with technical analysis, using stop loss to reduce risk. It needs additional research to adjust confidence level so VaR value is not too high that could fix trading strategy along this research.


The Mutual Agreement Procedure (Article 25 OECD Model Convention) is a rather helpful tool to sort out all kind of interpretation conflicts between two contracting states. If tax treaties are in an intra-Union setting replaced by a Directive and if the content of the OECD Model Convention is transformed in such a Directive, the Court of Justice would become competent to solve all interpretation issues. There does not seem to be room for a MAP any more. However, the author explains that the settled case-law of the Court of Justice allows to give some room for the MAP, although the Court of Justice has to have the last word.


Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.


The central and expanding role of the National Security Council (NSC) in drone and other extrajudicial killings of both U.S. citizens and citizens of other nations highlights the troubling and largely overlooked fact that, since the mid-1990s, the U.S. government has taken the categorical position that the NSC is exempt from both the documentation requirements of the Federal Records Act (FRA) and the disclosure requirements of the Freedom of Information Act (FOIA). Instead, the U.S. government treats all NSC records pursuant to the much less stringent, and nearly unenforceable, Presidential Records Act (PRA). The current situation undermines the ability to assess, evaluate, and, where appropriate, hold accountable the U.S. government for the extrajudicial killing of U.S. citizens and citizens of other nations. This obstacle to accountability obtains before a court adjudicating a wrongful death suit by the family members of people killed; it impedes deliberations by current and future government officials deciding whether to continue the program; it hinders Congress's role in evaluating whether to impose limits on the program; and it largely prevents future historians from meaningfully studying the extraordinary period in U.S. history when senior officials personally marked for death individuals beyond the borders. This article describes the NSC's expanding role in the drone killing program; the history of the NSC's relationship to the FRA, the PRA, and the FOIA; and the consequences of limited documentation requirements governing the NSC's involvement in the program, including implications of the lack of transparency and accountability for the expansion of executive power. The article argues for greater documentation and disclosure requirements for the NSC to ensure accountability to Congress, the public, and history regarding the current program of extrajudicial killings of U.S. citizens and citizens of other nations.


The financial statement analysis are elements of the financial planning. They are being used by investors and managers for professional investment or managerial decision making. Depending on the specific task, the analysis has different content and scale and every analyst compiles and applies its own method. No matter how the specific tasks are defined, it is always about identifying trends that serve to predict and on this basis for planning, i.e. the goal is to make a financial decision. The theory suggests a methodology that is studies based on differences in specific practical examples and in practice models are set up in which will be reflected the choice of goals and mediums.


MEDICAL SCIENCES Retraction for "Mutant surfactant A2 proteins associated with familial pulmonary fibrosis and lung cancer induce TGF-β1 secretion," by Meenakshi Maitra, Christopher A. Cano, and Christine Kim Garcia, which appeared in issue 51, December 18, 2012, of Proc Natl Acad Sci USA (109:21064–21069; first published December 5, 2012; 10.1073/pnas.1217069110). Christopher A. Cano and Christine Kim Garcia wish to note, "Current members of the C.K.G. laboratory are unable to reproduce key findings reported in the paper. Specifically, we cannot demonstrate a marked increase in ELISA-detectable TGF-β from HBEC-3KT cells expressing the mutant human surfactant proteins. Although the replication experiments could not be performed using the exact reagents as the original experiments, our current findings are not compatible with the conclusions of the published report. Accordingly, we have decided to retract the article at this time and apologize to our colleagues for any inconvenience this may have caused."


We calculate the shift in emission frequency of the trion and biexciton (relative to that of the single exciton) for nanocrystals (NCs) of inorganic perovskites CsPbBr3 and CsPbI3. The calculations use an envelope-function k.p model combined with self-consistent Hartree-Fock and a treatment of the intercarrier correlation energy in the lowest (second) order of many-body perturbation theory. The carriers in the trion and biexciton are assumed to have relaxed nonradiatively to the ground state at the band edge before emission occurs. The theoretical trion shifts for both CsPbBr3 and CsPbI3 are found to be in fair agreement with available experimental data, which include low-temperature single-dot measurements, though are perhaps systematically small by a factor of order 1.5, which can plausibly be explained by a combination of a slightly overestimated dielectric constant and omitted third- and higher-order terms in the correlation energy. Taking this level of agreement into account, we estimate that the ground-state biexciton shift for CsPbBr3 is a redshift of order 10-20 meV for NCs with an edge-length of 12 nm. This value is intermediate among the numerous high-temperature measurements on NCs of CsPbBr3, which vary from large redshifts of order 100 meV to blueshifts of several meV.


Management inaction can have disastrous consequences for firms despite many managers' belief that doing nothing does not impact performance. Doing nothing does something because management nonresponse to desirable or undesirable employee performance changes future worker behavior for the worse. Supervisory nonresponse to good employee performance sets the stage for extinction to occur which decades of research have demonstrated result in lower levels of desired conduct. Alternatively, supervisors who fail to address poor worker behavior may communicate to their subordinates that such undesirable performance is acceptable. Both practices lead to poor performance which can substantially damage firms.


Recent progress in semiconductor quantum-dot (QD) lasers approaches qualitatively new levels, when dramatic progress in the development of the active medium already motivates search for new concepts in device and system designs. QDs, which represent coherent inclusions of narrower bandgap semiconductor in a wider gap semiconductor matrix, offer a possibility to extend the wavelength range of heterostructure lasers on GaAs substrates to 1.3 /spl mu/m and beyond and create devices with dramatically improved performance, as compared to commercial lasers on InP substrates. Low-threshold current density (100 A/cm/sup 2/), very high characteristic temperature (170 K up to 65/spl deg/C), and high differential efficiency (85%) are realized in the same device. The possibility to stack QDs (e.g., tenfold) without an increase in the threshold current density and any degradation of the other device parameters allow realization of high modal gain devices suitable for applications in 1.3-/spl mu/m short-cavity transmitters and vertical-cavity surface-emitting lasers (VCSELs). The 1.3-/spl mu/m QD GaAs VCSELs operating at 1.2-mW continuous-wave output power at 25/spl deg/C are realized, and long operation lifetime is manifested. Evolution of GaAs-based 1.3-/spl mu/m lasers offers a unique opportunity for telecom devices and systems. Single-epitaxy VCSEL vertical integration with intracavity electrooptic modulators for lasing wavelength adjustment and/or ultrahigh-frequency wavelength modulation is possible. Arrays of wavelength-tunable VCSELs and wavelength-tunable resonant-cavity photodetectors may result in a new generation of "intelligent" cost-efficient systems for ultrafast data links in telecom.


Background NF-κB-inducing kinase (NIK) is a critical regulator of immunity and inflammation and NIK loss-of-function mutations have recently been described in patients with primary immunodeficiency disease. Based on our previous work showing that NIK regulates adaptive metabolic responses in glucose-starved cancer cells, we investigated whether NIK is required for mitochondrial functions in bioenergetic processes and metabolic responses to nutritional stress in NIK knockout (KO) mice, which recapitulate the clinical presentation of NIK PID patients. Methods We performed whole body composition analysis of wild type (WT) and NIK KO mice using EchoMRI and DEXA imaging. Seahorse extracellular flux analyses were used to monitor oxidative phosphorylation and glycolysis through oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) in preadipocyte cells and in ex vivo adipose tissue. NIK regulation of systemic metabolic output was measured by indirect calorimetry using TSE Phenomaster metabolic chambers under basal conditions as well as in response to nutritional stress induced by a prolonged high-fat diet (HFD). Finally, we analyzed a role for NIK in adipocyte differentiation, as well as the contributions of canonical and noncanonical NF-κB signaling to adipose development and metabolic output. Results We observed that in adipose cells, NIK is required for maintaining efficient mitochondrial membrane potential and spare respiratory capacity (SRC), indicators of mitochondrial fitness. NIK KO preadipocytes and ex vivo adipose tissue exhibited diminished SRC, increased proton leak, with compensatory upregulation of glycolysis. Systemically, NIK KO mice exhibited increased glucose utilization, increased energy expenditure, and reduced adiposity, which persisted under the stress of HFD. Finally, while NIK controlled adipocyte differentiation through activation of RelB and the noncanonical NF-κB pathway, NIK regulation of metabolism in preadipocytes was NF-κB/RelB-independent. Conclusion Our results demonstrate that NIK is required for metabolic homeostasis both locally, on a cellular and tissue level, as well as systemically, on an organismal level. Collectively, the data suggest that NIK KO cells upregulate glycolytic metabolism as a compensatory response to impaired mitochondrial fitness (diminished SRC) and mitochondrial efficiency (increased proton leak). To meet changes in bioenergetic demands, NIK KO mice undergo metabolic rewiring through increased glucose utilization and glycolysis, which persists under the stress of overnutrition with a HFD. Moreover, while NIK regulation of metabolism is RelB-independent, NIK regulation of adipocyte development requires RelB and activation of the noncanonical NF-κB pathway. Our findings establish NIK as an important regulator of cellular and systemic metabolic homeostasis, suggesting that metabolic dysfunction may be an important component of primary immunodeficiency diseases arising from loss of NIK function.


When a failure occurs in a network, network operators need to recognize service impact, since service impact is essential information for handling failures. In this paper, we propose Deep learning based Service Impact Prediction (DeepSIP), a system to predict the time to recovery from the failure and the loss of traffic volume due to the failure in a network element using a temporal multimodal convolutional neural network (CNN). Since the time to recovery is useful information for a service level agreement (SLA) and the loss of traffic volume is directly related to the severity of the failures, we regard these as the service impact. The service impact is challenging to predict, since a network element does not explicitly contain any information about the service impact. Thus, we aim to predict the service impact from syslog messages and traffic volume by extracting hidden information about failures. To extract useful features for prediction from syslog messages and traffic volume which are multimodal and strongly correlated, and have temporal dependencies, we use temporal multimodal CNN. We experimentally evaluated DeepSIP and DeepSIP reduced prediction error by approximately 50% in comparison with other NN-based methods with a synthetic dataset.


IntroductionAdministrative data are widely used to estimate epidemiologic indicators. The look-back period is needed to define baseline population for the incidence. However, short look-back period is known to overestimate incidence of diseases misclassifying prevalent cases to incident cases. A short look-back period with longer observation period causes misclassification more inconsistent.
Objectives and ApproachThe purpose of the study is to estimate the incidence rate of uterine leiomyoma by adjusting the misclassification error. We selected 319,608 women aged 15- 54 in 2002 from Korean National Health Insurance Service (KNHIS) cohort data. 34,445 cases were identified during 2002 - 2013. We applied 1-year look-back period as of 2003 and the actual look-back period increases with year, which incurs inconsistent misclassification error. Multiple regression model was used to estimate the number of incidence cases of the 11th look-back year for each year. Annual and adjusted annual incidence rates of uterine leiomyoma were calculated and compared.
ResultsThe annual number of patients(X1) is linearly related with the number of misclassification cases, and the number of misclassification cases are logarithmically associated with the look-back periods(X2). The regression equation was 0.07217 (y= 0.07217+ 0.00003213* X1 + 0.07992*ln(X2), R2=94.3). Crude incidence rate of uterine leiomyoma during the study period was 11.7% (35,992 cases) and adjusted rate was 10.5% (32,477cases). The annual incidence and adjusted annual incidence increased by 2.29 times and 2.86 times between 2003 and 2013, respectively. With look-back period of 11 years, 4,588(53.8 %) patients with uterine leiomyoma were estimated to have prior history of the disease.
Conclusion/ImplicationsWe proposed an adjustment for the misclassification error according to look-back periods. The method is applicable to estimate various healthcare events such as disease incidences and healthcare usage. Although the regression model showed very strong R-squared, follow-up study after several years is needed to validate the study results.


This paper explores how prudential regulations can support monetary policy in reducing output fluctuations while maintaining financial stability. It uses a new framework that blends a standard model for monetary policy analysis with a contingent claims model of financial sector vulnerabilities. The results suggest that binding countercyclical prudential regulations can help reduce output fluctuations and lessen the risk of financial instability. More specifically, countercyclical rules such as countercyclical capital adequacy rules, can allow monetary authorities to achieve the same output and inflation objectives but with smaller adjustments in interest rates. The countercyclical rules can help stem swings in asset prices, lean against a financial accelerator process, and thereby help to lower risks of macroeconomic and financial instability. In economies with fixed exchange rates, where countercyclical monetary policy is not possible, prudential regulations can provide a useful mechanism for mitigating a run-up in asset prices and for promoting output stability.


A regulated cross-couple charge pump with new charging current smoothing technique is proposed and verified in a 0.18- $\mu \text {m}~1.8$ -V/3.3-V CMOS process. The transient behaviors of 3-stage cross-couple charge pump and the expressions for the charging current are described in detail. The experiment results show that the charging current ripples are reduced by a factor of three through using the proposed new clocking scheme. The voltage ripples in the power supply line, which is connected with the charge pump input, are also smoothed greatly as the filter circuit does. The proposed scheme is used to decrease the smoothing capacitance in the power line of charge pump for reducing the size of implantable devices in biomedical application. In addition, the power efficiency is improved. The proposed cross-couple charge pump can provide 10.5-V output voltage with 3.5-mA output current, and the power efficiency of the charge pump can be up to 69%.


The study of ultra-high energy cosmic rays provides information about the hadronic interactions in an energy and kinematic region well beyond those explored in accelerators. The Pierre Auger Observatory is the largest cosmic ray observatory ever built (3000 km2), operating since 2004 in the Argentinian Pampa. Its hybrid design allows one to measure the longitudinal and lateral distribution of extensive air showers and the establishment of an almost model-independent, calorimetric, energy scale. The observatory is sensitive to the electromagnetic and to the muonic components of extensive air showers, which are directly related to the energy and type of the primary particle and to the hadronic interaction parameters. In this contribution an overview of the results obtained by the Auger collaboration in the field of particle physics will be given. We will show the proton-Air cross section at 38.7 and 55.5 TeV. Our data indicate that hadronic interaction models fail in the predictions of the muon densities on the surface, too low with respect to the measured ones. Possible future lines of research to investigate this inconsistency will be identified.


A throttle control apparatus includes a valve. A motor is provided for generating driving force to rotate the valve. Gears transmit the driving force to the valve. A biasing unit generates biasing force to bias the valve in a close rotative direction. A control unit is provided for supplying electricity to the motor to generate the driving force. When the control unit terminates electricity supply to the motor, the valve is biased to a full close position by the biasing force. When the control unit performs a full close control to manipulate the valve toward the full close position, the control unit continues electricity supply to the motor to stop the valve at a full close control point, which is set in advance of the full close position.


Ultraviolet irradiation (UV) induced cellular damage is classically associated with apoptosis and known to result in systemic immunosuppression. How the decision to undergo apoptosis is made following UV is not fully understood. We hypothesize that a central mediator of TLR signaling, MyD88, determines cell fate after UV. Survival after UV of immortalized bone marrow-derived macrophages (BMM) from MyD88 germline-deficient mice (MyD88-/-) was significantly higher and apoptotic morphology reduced, vs. wild-type (WT) BMM. UV-induced DNA laddering in peritoneal macrophages (PM) and epidermis of MyD88-/- animals, vs. WT, was decreased. In MyD88-/- PM, decreased cleavage of pro-necroptotic protein RIP1, elevated mRNA levels of RIP1 and RIP3, and significantly increased TNF-α release suggests that necroptosis rather than apoptosis has been initiated. In vivo studies after UV showed significantly less TUNEL-positive cells and more profound inflammation in MyD88-/- skin sections. MyD88-/- mice are also found to be resistant to UV-induced immunosuppression. Considering that MyD88 participates in many TLR pathways, TLR2-/-, TLR4-/-, and WT BMM were compared for evidence of UV-induced apoptosis. Only TLR4-/- BMM had a similar phenotype to MyD88-/-, suggesting that the TLR4-MyD88 axis importantly contributes to cell fate decision. Our study describes a new cellular consequence of MyD88 signaling after UV, and may provide rationale for therapies to mitigate UV-induced immunosuppression.


. Indoor Environmental Quality (IEQ) is a very important aspect in the de- sign of spaces. It depends on fundamental requirements, and it aims to improve living quality and ensure high well-being for the occupants. Poor IEQ has significant health consequences as people spend a considerable portion of their time indoors. The restrictions imposed by the current SARS-CoV-2 pandemic have worsened this situation by requiring people to spend more time at home and adopt home-working as a primary work model. Such a situation requires individuals to reconfigure their interior home spaces for adapting to new emerging needs. This paper proposes an approach based on reinforcement learning to support the rearrangement of indoor spaces by maximizing the indoor environmental quality index in terms of thermal, acoustic and visual comfort in the new furniture layout scheme.


When murder is the crime, the clash in the courts is likely to be between two constitutionally enshrined rightsfreedom of speech and the right to a fair trial.Peter E. Kane shows what happened in seven famous court cases when First Amendment rights (concerning freedom of speech) conflicted with Sixth Amendment rights (concerning fair trial). He reports the circumstances of each crime, the court proceedings, and the conduct of the press in the trials of Sam Sheppard, Charles Manson and his followers, John Paul Stevenson, Claus von Bulow, and Arthur Shawcross and the cases involving the Kellie family and the Wayne Clapp murders. Kane s narrative and analytical approach illuminates legal principles and shows the roles of actual human beings underlying the abstractions of court opinions.In this revised and expanded edition, Kane considers two new topics stemming from recent court cases: cameras in the courtroom and a code of ethics for crime reporting. Kane explores the issue of cameras through the famous Claus von Bulow retrial, which featured live television broadcasts; regarding a journalistic code, Kane examines the massive pretrial reporting of the serial murders of Arthur Shawcross. Kane notes that sensational crime stories serve the interests of many people: the public wants to read them; journalists want to write them because they can make a reporter s fortune and reputation; and editors and publishers want to sell papers. The sensational crime story serves everyone s purpose except that of the accused.In addition to exploring journalistic ethics and the proper procedures for trial judges in guaranteeing a fair trial, these cases also provide an introduction to the operation of the courts in criminal justice. "The trial court is the arena in which the conflicts between a free press and a fair trial are played out," Kane writes. "This play is described here as are the subsequent evaluations of that play by the appellate courts. Thus the legal process is considered from its beginning with the original crime to the final resolution of the case in the United States Supreme Court.""


The aim of this study was to test effects of age, gender, and sire line on dairy cattle behaviour. We have analyzed results of ethological tests for 40 Holstein breed animals (23 males and 17 females), offsprings of three sires. Maintenance behaviour were observed at the age of 90, 130 and 170 days. Behaviour in the maze was conducted at the age of 119 days, an open-field test was applied at the age of 124, 168, and 355 days. The social behaviour was determined by feeding on 155th day of the age. The times and the number of periods in all activities of maintenance behaviour were changing significantly (P<0.001) according to the age. The total time of lying, lying with ruminating, ruminating, feeding was increasing from the age of 90 days to the age of 170 days, on the other hand the time of standing was decreasing. The times of total lying, lying with ruminating, total ruminating, feeding were increased, and time of standing was decreased from the age of 90 days to the age of 170 days. Calves spent more time lying on the left side than on the right side. The number of ruminating periods was increasing according to the age. Eating periods were decreasing from the age of 90 to 170 days. The most of lying periods were recorded at the age of 130 days. The differences between sex were found in total time of lying, lying on the right side (P<0.05), and the males rest longer and had more periods of lying than females. We have found differences in times of feeding (P<0.001), total lying, standing (P<0.01), and lying on the left side (P<0.05) according to sire by comparing behaviour of the calves. Sire genotypes were significantly manifested in period number of total lying (P<0.001), lying on the right side, feeding (P<0.01), and standing (P<0.05). Males stood in the first part of maze longer than females (P<0.001), also length of total standing was longer by bulls (P<0.01). Heifers took shorter time to leave the maze than bulls (P<0.05). Sire lineages significantly differed in times of standing in the first part of maze and maze leaving. We did not find any significant differences either among sire lineage groups or between genders in locomotor behaviour measured by the number of crossed squares in open-field test. During all observations were more mobile heifers. No significant differences were found between males and females in social behaviour. The sire line influenced only the number of total duels (P<0.001). We found significant positive relationship between live body weight and time of staying in the first part of maze (r=0.3957**), time of maze leaving (r=0.3720**), and number of total and win duels (0.4031**, 0.3216*). Significant relationships were recorded in almost maintenance behaviour activities (P<0.001). Consistency of locomotor behaviour was proved only between the ages of 124 and 168 days (r=0.3177*). Significant relationship between maze behaviours and number of crossed squares were found only in ages of 119 and 124 days (r=-0.3721**; r=- 0.4110**; r=-0.3994**).


Cotranslational protein transport to the endoplasmic reticulum is controlled by the concerted interaction of three GTPases: the SRP54 subunit of the signal recognition particle (SRP) and the α- and β-subunits of the SRP receptor (SR). SRβ is related to ADP-ribosylation factor (ARF)-type GTPases, and the recently published crystal structure of SRβ-GTP in complex with the binding domain of SRα suggested that SRβ, like all ARF-type GT-Pases, requires a guanine nucleotide exchange factor (GEF) for function. Searching the sequence data base, we identified significant sequence similarity between the Sec7 domain of ARF-GEFs and the cytosolic domains of the β-subunits of the two homologous heterotrimeric protein-conducting channels in yeast. Using a fluorescence nucleotide exchange assay, we show that the β-subunits of the heterotrimeric protein-conducting channels function as the GEFs for SRβ. Both the cytosolic domain of Sec61β as well as the holo-Sec61β, when part of the isolated trimeric Sec61p complex, function as the GEF for SRβ, whereas the same Sec61β, when part of the heptameric complex that facilitates posttranslational protein transport, is inactive as the GEF for SRβ


Background: The oral PARP inhibitor olaparib (AZD2281, KU‐0059436) is in Phase II clinical trials in patients with BRCA‐mutated breast and ovarian cancer. Early results in these trials have provided positive clinical evidence for the targeted therapy concept of synthetic lethality using PARP inhibitors in molecularly‐defined tumors with little effect on normal tissues. However, olaparib offers the potential to treat a broader range of patient tumors and pre‐clinical studies have indicated that homologous recombination deficiency (HRD) due to loss of other DNA repair genes or through impaired cell‐cycle checkpoints can also lead to sensitivity to PARP inhibitors. The ability to stratify patients whose tumors will respond to treatment will be critical to realise the potential of this targeted therapy approach. In order to identify predictive biomarkers of olaparib response and to provide further insights into mechanisms of olaparib sensitivity a study was undertaken using a panel of cell lines correlating response with molecular profiles. Methods: A cross tumor‐type panel of 95 cell lines (KU‐95 panel) representing breast, ovarian, colorectal, lung, head & neck and pancreatic cancers was tested for sensitivity to olaparib using 2D‐clonogenic survival assays. Baseline (untreated) gene expression profiles using Affymetrix genome‐wide U133A 2.0 arrays together with protein expression and mutational status of genes, such as BRCA1, known to modify of olaparib response were determined for each cell line. Novel statistical, bioinformatics and pathway analysis approaches were used to identify genes that are predictive for olaparib response. Results: Across the KU‐95 cell‐line panel, 30 cell lines were highly sensitive to olaparib (IC50 4 M). Deleterious mutations in BRCA1 or BRCA2 genes were associated with only a small subset of highly sensitive cell lines indicating the presence of other factors able to modulate olaparib responsiveness. Directed analysis of several other DNA repair genes showed correlations with response consistent with previous data. Genome‐wide transcriptome and pathway mapping analysis revealed DNA repair and proliferation associated genes to be most consistently correlated with olaparib sensitivity. Based on results from all these approaches a candidate baseline gene expression profile predictive of olaparib response was established. Conclusions: By profiling a large panel of cell lines we have determined that factors in addition to BRCA mutation can be linked with olaparib sensitivity. A list of candidate gene transcripts was identified that predicts sensitivity to olaparib across a broad range of tumor types in vitro and may have utility as predictive biomarkers in the clinic. Studies are already underway to determine whether this baseline transcript tumor profile can be correlated with patient responses to olaparib. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C119.


AbstractThe aim of this essay is to analyse what roll repression has had in the making of my unpublished collection of poems entitled Hopp som i hare. I examine how the autobiographical subject abortion has influenced the writing process and the outcome of the poems. By presenting literature that's been important in the making of the collection I show some thoughts and ideas about Post Abortion Stress Disorder, a diagnosis without scientific grounds. In a discussion I go through the whole writing process from subject and genre choice through the revisions till the final version that were sent to be commented by the class in creative writing at Vaxjo University 2008. Finally I analyse my own reading before and after the workshop where the class commented the collection. It shows how repression influenced my reading before the workshop and how the class comments changed the way I red it afterwards. By hearing the class comment on my collection I also came to the conclusion that the poems was under repression and that constituted the ground of this essay.


When developing and maintaining a software system, programmers often rely on IDEs to provide editor services such as syntax highlighting, auto-completion, and "jump to declaration". In dynamic web applications, such tool support is currently limited to either the server-side code or to hand-written or generated client-side code. Our goal is to build a call graph for providing editor services on client-side code while it is still embedded as string literals within server-side code. First, we symbolically execute the server-side code to identify all possible client-side code variations. Subsequently, we parse the generated client-side code with all its variations into a VarDOM that compactly represents all DOM variations for further analysis. Based on the VarDOM, we build conditional call graphs for embedded HTML, CSS, and JS. Our empirical evaluation on real-world web applications show that our analysis achieves 100% precision in identifying call-graph edges. 62% of the edges cross PHP strings, and 17% of them cross files - in both situations, navigation without tool support is tedious and error prone.


This article is an investigation into the concepts of charity in the works of Emmanuel Levinas and Jean-Luc Marion. It consists, in the first place, of a critique of Levinas' concept of charity or love of neighbour, which, as appears in his later texts, is problematic. The problem arises when he equates charity with the moment of the bad conscience, experienced in relation with a particular other. In line of J-L Marion's critique of Levinas, I defend that charity, which is love for what is good for the unique other, cannot merely consist in suffering the bad conscience, because the bad conscience opens to the relation with the universal ethical injunction. Suffering bad conscience towards the concrete other is still the passive affection that one cannot hurt another (any other); it is not yet the relation of love, i.e., a relation in which one loves the other in his or her uniqueness. Secondly, the article is a critique of Marion's own concept of charity, defined, in response to Levinas, as love for the other in her/his uniqueness or the other as such. In defining his concept of love of neighbour as a relation of respect for the other, so I defend, Marion however ultimately equates it again with a relation with the universal ethical injunction, commanding one to respect every possible other rather than working up love for the uniqueness of the other. In response to Levinas and Marion I argue, in the final part of the text, for a necessity of the distinction between the passive moment of the bad conscience and the active moment of love of neighbour. Suffering bad conscience is surely the warning for the ethical fault, but this moment of passive accusation does not yet explain why one loves what is good for the other. As I will defend, such love includes a moment of wishing for or desiring what is good for the other in his/her uniqueness.


From an Escherichia coli K-12 strain lacking adenylate cyclase (cya) and cyclic AMP receptor protein (crp), two mutants were isolated that synthesize uridine phosphorylase constitutively. The mutations differ from one another and also from a wild type in the maximum rate of uridine phosphorylase synthesis. They have constitutive expression of the uridine phosphorylase gene (udp) in the presence of repressor protein coded by the cytR regulatory gene and decrease the sensitivity of the udp gene simultaneously with catabolite repression. Both mutations cause a high level of udp expression whether they are in a cya crp or in a cya+ crp+ background. Another mutation (udpP1) isolated previously alters the response of udp gene to the ctyR repressor and produces a higher constitutive level of uridine phosphorylase in a cytR+ than in a cytR background when bacteria are grown in glucose. The synthesis of uridine phosphorylase in this mutant is dependent on an intact cyclic AMP-cyclic AMP receptor protein complex. All mutations studied are cis-acting and extremely closely linked to the udp structural gene, and appear to affect the uridine phosphorylase promoter-operator region. The data obtained are in accordance with a suggestion that the cytR repressor protein normally asserts its function by preventing the positive action of cyclic AMP-cyclic AMP receptor protein complex.


The HaCaT cell line represents the spontaneously immortalized non-carcinogenic human keratinocytes that are used as a model for studying the function of normal human keratinocytes. There are two TP53 alleles in the HaCaT cell genome, which comprise two gain-of-function (GOF) mutations acquired through spontaneous immortalization (mutTP53). Mutations result in the increased proliferation rate and violation of the stratification program. The study was aimed to assess the effects of the mutTP53 gene knockout on the HaCaT keratinocytes capability of proliferation and migration in the in vitro model of epidermal injury and regeneration (scratch test), and on the ability to form stratified epithelium in the organotypic epidermal model. To perform the scratch-test, cells were cultured until monolayer was formed, then the standardized injury was created. The organotypic model was obtained by growing keratinocytes in the polycarbonate membrane inserts with the pore size of 0.4 μm at the interface between the phases (air-liquid). It has been shown that the mutant TP53 gene knockout results in the increased migration capability of the HaCaT keratinocytes: in the HaCaT with the mutTP53 knockout, the defect closure occurred faster than in the appropriate group of the WT HaCaT (p < 0.05), on day three the defect size was 12% ± 3% and 66% ± 5% of the initial size. There is evidence that mutant TP53 in the HaCaT cells is a negative regulator of the laminin 5 expression (LAMC2 expression was 9.96 ± 1.92 times higher in the cells with the mutTP53 knockout, p < 0.05), however, this does not promote normalization of the program of epithelial differentiation and stratification followed by formation of the stratum corneum in the organotypic model.


OBJECTIVE
Dysfunction of autophagy has been implicated in development and progression of diverse human cancers. However, the exact role and mechanism of autophagy have not been fully understood in human cancers, especially in retinoblastoma (Rb).

PATIENTS AND METHODS
We determined the autophagy activity in human Rb tissues by assessing the autophagy markers microtubule-associated protein light chain 3B (LC3) and p62 (SQSTM1) in formalin fixed and paraffin embedded human tissue by immunohistochemistry and then associated their expression with patient clinicopathological features. We further explored the correlation between the expression of LC3B and p62 and the expression of cytoplasmic p53, a newly identified autophagy suppressor, in Rb tissues.

RESULTS
Our data revealed that the expression of LC3B and p62, was significantly associated with disease progression and tumor invasion of Rb. Furthermore, we also revealed that cytoplasmic expression of p53 was inversely associated with the behavior of tumor invasion. Finally, Spearman correlation analysis demonstrated that cytoplasmic expression of p53 was significantly and inversely correlated to the expression of both LC3B and p62.

CONCLUSIONS
Autophagy might play an important role in human Rb progression, and LC3B and p62 may be useful predictors of disease progression in patients with Rb.


The aim of the present work is to design active acoustic metamaterial consisting of an array of Helmholtz resonators and fabricating them using additive manufacturing technique in order to assist in reduction of noise levels in aerospace applications. To this aim, initially, a passive metamaterial consisting of an array of 64 Helmholtz resonator unit cells is designed and tested to establish the effectiveness and region of performance. The selected design variable for change is identified as the resonator cavity depth through the frequency response for each parameter of the Helmholtz resonance equation and randomized to achieve a broadband frequency range of the passive metamaterial. An active model of this design (actuated by a stepper motor) is fabricated and tested. The metamaterials are tested under two acoustic set-ups: a closed system aimed at recreating the environment of a soundproof room and an open-system aimed to recreate the condition of an active liner. For the case of passive system, the metamaterial gave sound attenuation of 18 dB (for f=150 Hz) in open system configuration and 33 dB (f=350 Hz) in closed system configuration. The attenuation obtained for the active model was 10–15 dB over the mean line performance for the case of closed system and 15–20 dB for the case of open system. The closed system was also tested for performance at multiple cavity depths by setting two wall depths at 10 mm and three walls at 50 mm. This test yielded an attenuation of 15 dB at 180 Hz, the frequency corresponding to 50 mm cavity depth, and 10 dB at 515 Hz, corresponding to 10 mm cavity depth.


The role of Kenya National Union of Teachers in enhancing quality education in Kenya cannot be over emphasized. Despite the role of Kenya National Union of Teachers (KNUT) on teachers' performance in Public Primary Schools, Rachuonyo North Sub-County continues to pose unimpressive negative deviation index in Kenya Certificate of Primary School Education (KCPE). The purpose of this study was to investigate the influence of KNUT  on teacher timely syllabus coverage' in public primary schools in Rachuonyo North Sub-County.  Employing Descriptive Survey Design, this study adopted Committed and Work Engagement Goals Theory. Five hundred and forty nine  (549)  respondents were sampled out as follows:- Headteachers (55), KNUT school representatives (55),Std 8 class teachers (55),  other school subject teachers (337 out of  55 selected primary schools), KNUT executive officials (4) and 330 School Management Committee members, from 55 primary schools. Questionnaires, interview schedules and focus group discussion guide were used to collect data as the instruments were used due to their flexibility and adoptability. The validity of the research instrument was ascertain by use of a five—point Likert scale rating by experienced experts to ascertain whether questions were relevant, while the reliability was ascertain by test re-test technique using pilot study. Both validity and reliability depended on accuracy of research instrument i.e; technique procedure and findings. Heterogeneous aspects of the respondents were considered, including respondents ability, clarity of instructions and nature of construction. The instruments was administered for twelve weeks, then data was sorted, edited and coded for the purpose of allocation and entered for analysis using the Statistical Package for Social Science (SPSS version 22).Data from interviews and Focus Group Discussion were analyzed qualitatively in an on- going processes as  themes and sub—themes emerged from the data. Quantitative data were analyzed using percentages, frequencies and bar-graphs. Inferential statistics were used to help making inferences and draw conclusions. The findings of the study asserted that KNUT has enabled teachers to improve in curriculum content implementation in-terms of syllabus coverage to enhance academic performance.


The representation and archiving of design information play an essential role in product conceptual design by enabling the design teams to reuse existing solutions. However, most existing studies on information management of conceptual design focus mainly on the systematisation of function related design knowledge, while few studies are related to the aesthetic aspect of design information. The challenge lies in acquiring and quantifying the aesthetic information involved in conceptual design activities. It is also difficult to represent and archive the relationships and hierarchies of aesthetic information in conceptual design. In this context, this study proposes a method to facilitate the searching and retrieval of existing design solutions with effective representation and archiving of both functional and aesthetic information in conceptual design. Firstly, to address the challenge of acquiring and quantifying the aesthetic information, Kansei adjectives and aesthetic design principles were applied to quantify the aesthetic design information. Secondly, a model using knowledge-based information representation and an approach for archiving conceptual design information was proposed to represent and archive the aesthetic information in hierarchal relationships. The proposed approach was illustrated by a case study of digital camera design. A system prototype with a domain-driven vocabulary to represent and archive aesthetic information for digital camera design was successfully developed to show the feasibility of the proposed approach.


Purpose Following coronary artery bypass graft (CABG) surgery, some patients experience psycho-mental problems such as hopelessness. The Phase 2 cardiac rehabilitation (CR) program is an important element of the secondary prevention program in treating patients with cardiovascular disease (CVD). The present study aimed to determine the effect of the Phase 2 CR program on the level of hope in cardiac patients after CABG surgery. Patients and Methods A clinical trial was conducted from July 2017 to late January 2018 at the Heart Surgery Centre, Al-Zahra Hospital, Shiraz, Iran. The target population was patients who sought CR therapy after CABG surgery. A total of 104 cardiac patients were recruited and equally divided into control and intervention groups. The intervention group received 20 sessions of Phase 2 CR program combined with education and counselling during 8 weeks. The control group only received routine observations and education. The data were collected pre- and post-intervention using a demographic form and the Miller Hope Scale (MHS). Descriptive statistics were expressed as percentages, frequency distribution, mean and standard deviation. Paired t-test and independent t-test were used for statistical inference. Data were analyzed using the SPSS statistical software (version 23.0) and P values <0.05 were considered statistically significant. Results There was no significant difference in the mean score of hope between the control and intervention groups before the intervention. However, a significant difference between the groups was observed post-intervention (P<0.001). The results showed a significant difference in the mean score of hope between pre-intervention (182.36±23.07) and post-intervention (216.94±23.05) in the intervention group (P<0.001), whereas the difference in the control group was not significant (P=0.095). The measured post-intervention effect size was high (1.05). Conclusion The Phase 2 CR program combined with education and counseling increased hope in CVD patients after CABG surgery.


The use of buyer/planners may becoming more popular. If they are, the reason is probably that many companies are integrating materiel management skill sets as a way of increasing the effectiveness of their supply chains. Harley-Davidson recently created a supply management function composed of buyer/planners. This article describes the method it used to achieve the transition, the training plan it implemented to support the process, and the role management played in achieving success.


AIM
Development of effective medications for the treatment of cocaine dependence remains a major priority for the National Institute on Drug Abuse (NIDA) at the National Institutes of Health. The Cocaine Rapid Efficacy Screening Trial (CREST) paradigm was developed by the Division of Treatment Research and Development (DT R&D) at NIDA with the goal of enhancing pilot clinical trial validity when systematically assessing a range of medications and drug classes for potential utility in treatment of cocaine dependence.

DESIGN
CREST utilizes a randomized, controlled, parallel group, blinded methodology for comparing one or more marketed medications against a standard, pharmaceutical grade placebo. The trial design is comprised of a flexible 24-week screening/baseline period followed by randomization to an 8-week treatment period.

MEASURES
Standard measures of outcomes for the CREST included urinary benzoylecgonine (primary metabolite of cocaine), retention, cocaine craving, depression, clinical global impression and HIV-risk behaviors. In order to facilitate comparisons of data from the CREST studies across sites, drug classes and time, standardized procedures, measures and psychosocial counseling were used.

RESULTS
A total of 19 medications were evaluated in out-patient treatment research clinics in Boston, Cincinnati, Los Angeles, New York and Philadelphia.

CONCLUSIONS
Findings supported decisions to move forward three medications (cabergoline, reserpine, tiagabine) using full-scale, adequately powered, randomized placebo-controlled trial designs. Lessons learned from the CREST experience continue to shape cocaine pharmacotherapy trial design and execution.


Hardware-in-the-loop testing is usually a part of the design cycle of control systems. Efficient and fast models can be created in a Hardware Description Language (HDL), which is implemented in a Field-Programmable Gate Array (FPGA). Control engineers are more skilled in higher-level approaches. HDL models derived automatically from schematics have noticeably lower performance, while HDL models derived from their equations are faster and smaller. However, even models translated automatically into HDL using the equations might be worse than manually coded models. A design workflow is proposed to achieve manual-like performance with automatic tools. It consists of the identification of similar operations, forcing signal signedness, and adjusting to multiplier input sizes. A detailed comparison was performed between three workflows: (1) translation of high-level MATLAB code, (2) translation of a Simulink model, and (3) working directly in the HDL. Sources of inefficiency were shown in a buck converter, and the process was validated in a full-bridge with electrical losses using a Runge–Kutta method. The results showed that the proposed approach delivered code that performed very close to a reference VHDL implementation, even for complex designs. Finally, the model was implemented in an off-the-shelf FPGA board suitable for a hardware-in-the-loop test setup.


Optimization is often cast as a deterministic problem, where the solution is found through some iterative procedure such as gradient descent. However, when training neural networks the loss function changes over (iteration) time due to the randomized selection of a subset of the samples. This randomization turns the optimization problem into a stochastic one. We propose to consider the loss as a noisy observation with respect to some reference optimum. This interpretation of the loss allows us to adopt Kalman filtering as an optimizer, as its recursive formulation is designed to estimate unknown parameters from noisy measurements. Moreover, we show that the Kalman Filter dynamical model for the evolution of the unknown parameters can be used to capture the gradient dynamics of advanced methods such as Momentum and Adam. We call this stochastic optimization method KaFiStO. KaFiStO is an easy to implement, scalable, and efficient method to train neural networks. We show that it also yields parameter estimates that are on par with or better than existing optimization algorithms across several neural network architectures and machine learning tasks, such as computer vision and language modeling.


Background Thoracic endovascular aortic repair (TEVAR) has been increasingly used for the treatment of descending thoracic aortic aneurysms and dissections. This study sought to evaluate the influence of sex on outcomes after TEVAR. Methods and Results This was an observational study from the Nationwide Readmissions Database analyzing all patients who underwent TEVAR from 2010 to 2018. Sampling weights were used to generate national estimates. International Classification of Diseases-Clinical Modification codes were used to identify patients with thoracic aortic aneurysms or dissections who underwent TEVAR. Patients were dichotomized according to sex, and 1:1 propensity score matching was applied. Mixed model regression for in-hospital mortality and weighted logistic regression with bootstrapping for 30-day readmissions were performed. A supplemental analysis was performed according to pathology (aneurysm or dissection). A weighted total of 27 118 patients were identified. Propensity-matching yielded 5026 risk-adjusted pairs. Men were more likely to undergo TEVAR for type B aortic dissection, whereas women were more likely to undergo TEVAR for aneurysm. In-hospital mortality was roughly 5% and was equivalent in the matched groups. Men were more likely to have paraplegia, acute kidney injury, and arrhythmias, while women were more likely to require transfusions after TEVAR. There were no significant differences in myocardial infarction, heart failure, respiratory failure, spinal cord ischemia, mesenteric ischemia, stroke, or 30-day readmission between the matched groups. On regression analysis, sex was not an independent risk factor for in-hospital mortality. Female sex was, however, significantly associated with a decreased odds of 30-day readmission (odds ratio, 0.90 [95% CI, 0.87-0.92]; P<0.001). Conclusions Women are more likely to undergo TEVAR for aneurysms, while men are more likely to undergo TEVAR for type B aortic dissection. In-hospital mortality after TEVAR is comparable among men and women irrespective of indication. Female sex is independently associated with a reduced odds of 30-day readmission after TEVAR.


A family risk index was developed that compares the distribution of an endpoint in all families (regardless of disease status) with multiple, random, internal comparison groups. This index incorporates the person-time approach to adjust for risk due to age, birth cohort, sex, and race. It was validated and applied to a population-based sample of 51,714 individuals in 3,277 families from metropolitan Detroit to evaluate the role of familial risk factors in the development of cancer. Interviews took place between June 1973 and July 1977. A measure of familial heterogeneity of risk was used to determine whether cancer risk in families differed from cancer risk in randomly generated comparison groups of the same age, sex, race, birth cohort, and size distributions. For cancers of all sites combined, familial heterogeneity of risk was expressed in the study sample both as lower risk than expected among some families and as higher risk than expected among some families. It is estimated that 27% of the variability in cancer occurrence in the families is due to familial factors.


Abstract Improving efficacy of inflammation treatment by increasing drug delivery to the inflammatory sites is a challenging endeavor. N-formyl-methionyl-leucyl–phenylalanine (fMLP), the first discovered leukocyte chemotaxis peptide, is composed of formyl methionine, leucine and phenylalanine. It conjugates with formyl peptide receptors on the target cells with high receptor expression on the surface such as macrophages. With this in mind, we developed a novel fMLP-modified liposome (fMLP–LIP) for enhancing drug delivery to the inflammatory sites and resolving the systemic reaction issue with conventional anti-inflammatory drugs. Being a more stable and cheaper liposomal component than phospholipids, cholesterol (CHO) has been thoroughly investigated as an alternative anchor. In this study, fMLP was covalently conjugated with CHO with polyethylene glycol link to prepare the liposomes, cellular uptake of liposomes by differentiated human U937 cells was examined and cellular uptake experiment in vitro was employed to optimize fMLP–LIP prescription and investigate the uptake mechanism. An in vivo inflammatory model was established to evaluate the targeting performance of fMLP–LIP to inflammatory site. The in vitro and in vivo findings indicate that the fMLP ligands playing an important role in increasing drug delivery to inflammatory sites and fMLP–LIP as a promising anti-inflammatory drug carrier.


David Kohls' story, like those of most Strimple awardees, is a love story. It is because of David's love for fossil insects that he has dedicated so many years to the careful collection and study of Eocene insects from the Green River Formation. He has made important contributions to the field through the outstanding specimens he has collected and donated, through his scientific presentations, and through his persistence and ability to bring together local geologists and international researchers. I first met David when I was a graduate student looking for localities, but then I was fortunate to reconnect with him when I took up my position at the University of Colorado. We have worked together now for over 8 years.

Let me start by describing David's work process. In the spring, when the outcrops are covered with snow, David and I talk about a plan for the coming year. He plots out when and where to collect and with whom he plans to meet. In …


What does accountability mean in the context of public education? Many charter school advocates often argue that charters are superior to traditional public schools because they are more accountable but do not identify how they are accountable or to whom. This article interrogates the meaning of "accountability" in the conversation about charter schools, particularly in the context of Philadelphia, where over one third of the public school population is enrolled in charters and charter funding occupies approximately 40 percent of the Philadelphia School District budget.

I argue that accountability should go beyond simply market accountability in the form of parental choice. Oversight of charters is essential if the Commonwealth is to fulfill its obligation to provide a thorough and efficient system of public education to the residents of Pennsylvania. Pennsylvania has a primary constitutional obligation to provide public education. To the extent those in government decide to include charters in the mix of how that education is provided, they must ensure oversight of the funds provided for charters to avoid use of public funds that are spent to the detriment, not the benefit, of Pennsylvanians. This article provides a granular examination of the charter application process in Philadelphia.

The Philadelphia School District's Charter Schools Office (CSO) has developed best practices for oversight which have increased the information available to the public about the education, finances, governance, and regulatory compliance of the charters it oversees. It carefully and extensively evaluates applications for new charters and requests for renewal. But the reaction to this effort has been hostility from those who appear to think that oversight equals attack, rather than careful stewardship of public funds. True accountability should involve careful oversight and not blind approval of anything a charter school operator chooses to do with the public money entrusted to it.


+e function of 1-methylcyclopropene (1-MCP) in the regulation of quality and antioxidative system of mango fruit was investigated during storage at ambient temperature. Changes in fruit quality, colour, ethylene production, respiration rate, fruit softening enzyme activities, and antioxidative enzyme activities were studied in this study. +e results demonstrated that 1-MCP was beneficial for maintaining quality. 1-MCP treatment retarded the decline of firmness, weight, total soluble solid, and titratable acidity, which served as significant parameters for assessing fruit quality in the process of storage. Compared with the fruit of the control group, the treatment with 1-MCP dramatically delayed the colour change of both the pulp and peel and suppressed climacteric peaks of ethylene generation and respiration speed.+e significant inducement of peroxidase, catalase, and superoxide dismutase activities were followed by 1-MCP treatment. +e fruit treated with 1-MCP displayed significantly inhibited activation of enzymes on the cell wall, i.e., pectin esterase (PE), endo-1,4-β-d-glucanase (EGase), exopolygalacturonase (exo-PG), and endopolygalacturonase (endo-PG), during storage. +e results suggested that 1-MCP imposed underlying impact on the maintenance of the softening and extension of postharvest life of mango fruit.


Protein adsorption on surfaces occurs shortly after scaffold insertion. This process is of pivotal importance to achieve therapeutic success in tissue engineering (TE), and favorable proteins should be adsorbed at the interface without unfolding to preserve their structure and function. Protein misfolding at the interface is a common phenom‐ enon, which can impair cell adhesion and scaffold colonization. Many efforts have been done to improve scaffold biocompatibility by ameliorating protein adsorption, but with poor results. In the present chapter, we propose the use of a novel class of molecules, aptamers, to improve scaffold biocompatibility. Aptamers are small, single stranded oligonucleotides, which specifically bind to a target molecule: they work as antibod‐ ies, but without many of the drawbacks associated to the use of antibodies. We propose to immobilize aptamers on scaffolds to retain specific proteins, acting as docking points to guide cell activity. In particular, we show the results obtained by enriching different polymeric scaffolds with aptamers against human fibronectin, a naturally abundant protein in tissues, which plays a pivotal role in cell adhesion. We demonstrate that scaffold enrichment with aptamers lead to a better colonization of the substrate from cells. The results we obtained pave the way to the possibility of further investigating the role of aptamers as useful molecules to improve scaffold biocompatibility in the contest of tissue engineering.


Although, it is a long time that human know about the importance of environment in life, but at the last decade of 20 century, the space that was full of hot scientific, collegial and political were made in environmental challenge, So much that, this problem not only disarrange the peace and security of life, but also it has threatened human existence. One of the problems in last years that are significant for authorities is unsatisfactory achieved results against of using huge cost for magnificent environmental projects. This subject leads thinker to this thought that for solving the environmental problems it is needed new methods include of sociology, ethics and philosophic, etc. methods apart of technical affairs. Environment ethics is a new branch of philosophic ethics discussion that discusses about the ethics relationship between humans and universe that is around them. By notifying to the above considered affairs, in today world, necessity of environmental ethics for environment management is reduplicated. In the following the article has been focused on environmental ethics role and environmental management methods and techniques for developing


The 11q23 chromosomal abnormality is frequently observed in infantile leukemia and secondary leukemia, and the translocation associated gene in infantile leukemia is called mixed-lineage leukemia (MLL) gene. A 50-year-old man was admitted because of left axillary lymphadenopathy and IBL like T cell lymphoma was diagnosed by lymph node biopsy. The patient responded to the LSG-9 protocol with complete remission. After 10 months he was readmitted because of fever and was diagnosed acute myeloblastic leukemia by bone marrow aspiration. Chromosome analysis revealed 11q23 abnormality, suggesting that the leukemia was induced by etoposide treatment. Southern blot analysis demonstrated DNA rearrangement in the MLL gene at 11q23. It was suggested that the breakpoint region of the MLL gene in secondary leukemia is the same as that of infantile leukemia.


Background: Several problems are associated with manual muscle testing and dynamometry in the hands of patients with Charcot–Marie–Tooth (CMT) disease. Objective: To evaluate the efficacy of the Rotterdam Intrinsic Hand Myometer (RIHM) to directly measure intrinsic hand muscle strength in CMT disease. Methods: We measured hand muscle strength and hand function in 41 patients with CMT disease. Results: RIHM measurement of intrinsic strength had excellent reliability. We found overlapping RIHM strength values in Medical Research Council grades 3 to 5. High grip and pinch strength could be found in patients with severe intrinsic muscle weakness. RIHM measurements were more strongly correlated with fine motor skills of the hand than grip and pinch strength. Conclusions: The Rotterdam Intrinsic Hand Myometer is a reliable instrument to measure intrinsic hand muscles strength in patients with Charcot–Marie–Tooth disease, providing more detailed information than manual muscle testing and a more direct assessment of intrinsic muscle loss than grip and pinch dynamometers.


A critical analysis of aesthetical views by Pierre Francastel, a well-known French art sociologist and art critic, is presented. The author's attention is focused on solving the problem of interaction of art and technology. A number of constructive points of the theory by Francastel are singled out, such as, the accent of polysemantic character of a work of art, the growth of intellectual basis in creative work, etc.


Hypoxia is associated with aggressive and poor prognosis of breast cancer. Generally, pan-genome analyses of hypoxia have focussed on protein-coding genes, however, the role of non-coding RNAs, in particular long non-coding RNAs (lncRNA) in hypoxia is not well characterised. We undertook an integrated genomic analysis of the hypoxic transcriptome in MCF7 breast cancer cells, employing total RNA-seq together with ChIP-seq for the hypoxia-inducible transcription factor (HIF) and for epigenetic marks of transcriptional activation (RNApol2 and histone H3K4me3). Analyses revealed that all classes of RNA are significantly regulated by hypoxia including piwiRNA, miRNA, tRNA, and sn/snoRNA. Significant numbers of lncRNAs were upregulated in hypoxia and were associated with increased RNApol2 and H3K4me3 markers and with HIF binding, indicating direct transcriptional activation of lncRNAs by HIF. The most hypoxiclly upregulated lncRNA was NEAT1, which is a direct transcriptional target of HIF-2a but not HIF-1a. The role of NEAT1 in cancer has not been previously studied. We demonstrated that hypoxic NEAT1 induction is common in breast cancer cell lines and xenografts models treated with bevacizumab. NEAT1 directly induces the formation of nuclear paraspeckle bodies in hypoxia. Moreover, it contributes to tumourigenicity by increasing cell proliferation, colony formation, and reducing apoptosis. In addition, we report that NEAT1 is required to retain hypoxia induced hyper edited Junctional Adhesion Molecule A (JAM-A) mRNA in the nucleus, thus preventing export into the cytoplasm for translation. Finally, in a large cohort of 2000 breast cancers, high levels of NEAT1 were associated with poor clinical outcomes and clinicopathological features. Our results extend knowledge of the hypoxic transcriptional response into the spectrum of non-coding transcripts. These findings provide novel mechanisms of transcriptional regulation in hypoxia and open new avenues to find novel pathways and targets to develop therapies for breast cancer. Citation Format: Hani Choudhry, Johannes Schodel, Ashwag Albukhari, Syed Haider, Francesca Buffa, Peter J Ratcliffe, David R Mole, Ioannis Ragousis, Adrian L Harris. The non-coding transcriptome of hypoxic breast cancer: Novel insights of clinical relevant long non-coding RNA in hypoxia signalling [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-01.


We obtain the primitively divergent diagrams in $\kappa$-deformed scalar field in four-dimensional spacetime with quartic self-interaction in order to investigate the effect of the fundamental length $q=1/(2\kappa)$ on such diagrams. Thanks to $\kappa$-deformation, we find that the dimensionally regularized forms of the diagrams lead to finite results in the limit of space-time dimension four. The effect of the deformation appears as a displacement of the poles in the complex plane.


Solar energy is used mainly in two forms, as thermal energy and as electrical energy. On the one hand, in most applications where thermal energy is used, electrical energy is also required. On the other hand, photovoltaic systems utilise only a fraction of the incident solar energy, and the rest is wasted in the form of heat. Besides, silicon cells perform poorly at high operating temperatures, thus cooling of the cells is beneficial. Though concentration of sunlight enhances photovoltaic cell output, the high temperature associated with it prohibits its effective application. A hybrid collector is designed in such a way that the surface of the collector is partially or completely covered by photovoltaic cells, while a circulating fluid stream passes through the top and/or bottom sides of the collector plate, carrying away the excess heat and thus maintaining the cells at their optimum operating temperature. For the past twenty years very few studies of actual experimentations of the photovoltaic thermal air heaters have been conducted. Most studies have concentrated on simulations to determine the performance of such systems.


Cadmium telluride is a semiconductor material which is now widely used in both spectroscopic and imaging applications. Among its properties, the most advantageous is its ability to operate at room-temperatures, so as to avoid the need for bulk cooling devices. Nevertheless, a quantitative evaluation of the temperature dependance of the detectors response is needed in order to establish a temperature range for safe operation. In this paper, some parameters are evaluated at temperatures ranging from -35/spl deg/C up to 40/spl deg/C with an energy source of 511 keV for a set of three spectroscopy grade CdTe detectors. The data obtained seem to indicate a significant temperature independence below O/spl deg/C, while at temperatures over 10/spl deg/C spectra degradations occur.<<ETX>>


Background/Case Studies: FDA guidance, finalized in December 2020, requires large-volume delayed sampling (LVDS) with a 12-h hold prior to release to reduce the risk of bacterial contamination of platelet products. Microbially contaminated products accounted for 24 (13%) fatalities reported to the FDA for fiscal years 2016–2020, with bacterial contamination of platelets accounting for 10 of the 24. However, the initial hold for the first 12 h of incubation reduces the available time on this product for use in a patient. Our center gathered retrospective data to determine the effectiveness of the 12-h hold in preventing release of contaminated products. Study Design/Methods: Our center's blood establishment computer system was queried for all apheresis platelet culture data, including the number of hours after incubation that bacterial culture samples flagged positive, from inception of LVDS. In addition, confirmatory gram stain and agar plate culture results were abstracted for those platelet products that initially flagged positive. Results/Findings: Since implementation of LVDS in 2021, our center has had 52 apheresis platelet products that initially flagged positive on an automated culture system (BacT Alert Virtuo, BioMerieux). The average length of time to a positive flag was 61 h after inoculation, or 109 h following collection. Of the total 52 positive flags, 6 (11.5%) flagged positive within the 12-h hold period. Of the six that flagged positive, four showed organisms on gram stain that were able to be cultured on agar and identified, equating to a true positive rate of 66%. Data presented last year by our center showed a true positive rate of 37.5% when looking at all positive flags during the entire 6-day incubation period. Although the true positive rate during the 12-h hold appears higher than the rate during the entire incubation period, the data sets are too small to show statistical significance. The organisms recovered in the four that showed growth on agar were: one bacillus cereus group, two streptococcus gallolyticus ssp pasturianus, and one Streptococcus mitis/Streptococcus oralis. Conclusions: Since the implementation of LVDS, our center's data show that we have had 52 apheresis platelet products initially flag positive with flags occurring on average 61 h after incubation but with 6 flagging within the 12-h hold. True positive rate for flags within the 12-h hold is 66%, appearing to be higher than the true positive rate of 37.5% seen overall for all positive flags, although the numbers are too small for statistical significance. More data are needed to determine if this trend persists. Importantly, in our experience, the 12-h hold has prevented the release of four contaminated units to patients.


Shock-induced melt veins in the Acfer 040 L5-6 (S6) chondrite contain a previously unknown set of high pressure phases consisting of amorphous grains similar in composition to majorite, MgSiO3-ilmenite, and ringwoodite. The amorphous grains have compositions that are similar to those of synthetic MgSiO3-perovskites from chemically complex systems and are inferred to be MgSiO3-perovskite that crystallized from the melt at high pressure and temperature and subsequently amorphized after pressure release. The ilmenite represents a natural occurrence of a potentially important mineral in Earth9s mantle. The MgSiO3-perovskite–MgSiO3-ilmenite–ringwoodite assemblage is not predicted by phase equilibria studies, but appears to result from crystallization of a melt at pressures above 26 gigapascals.


OBJECTIVE
To investigate the feasibility of host endothelialization of transplanted hetero-heart valve by transfer of VEGF gene.

METHODS
Bovine pericardium treated with glutaraldehyde and L-glutamine was positioned into ping's right atrium, then gene suture carrying plasmids with pcD2/hVEGF121 gene or only with pcD2 was sewn into the anterior wall of right ventricle. The contents of VEGF protein in blood from right atrium and peripheral vein were determined by ELISA 10 days after the transplantation. The expression of VFGF mRNA in the myocardium near the gene suture was detected by RT-PCR 16 days after the transplantatipn. Microscopy and unltrastructural analysis of the transplanted valve were carried out.

RESULTS
The content of VEGF protein in blood from the right atrium in the pcD2/hVEGF121 group was significantly higher than that in the pcD2 group 10 days after the VEGF gene transfer (P < 0.01). The expression of VEGF mRNA in the myocardium of right ventricle in pcD2/VEGF121 group was much higher than that in the left ventricle of the same group and that in the right ventricle in pcD2 group. Morphological observation showed that the coverage rate of host endothelium in pcD2/hVEGF121 group was higher than in pcD2 group 16 days after the gene transfer (P < 0.05). 30 days after the gene transfer. Complete host endothelialization was observed 30 days after the operation.

CONCLUSION
VEGF gene transfer with surgical suture promotes the host endothelialization of bioprothesis, thus inhibiting calcification of biological valves and improving biocompatibility and long-term durability of bioprothesis.


The problem of a circular elastic inclusion in a thin pressurized spherical shell is considered. Using Reissner's differential equations governing the behavior of a thin shallow spherical shell, the solutions for the two regions are obtained in terms of Bessel and Hankel functions. Particular cases of a rigid circular inclusion free to move with the shell and a clamped rigid circular inclusion are also considered. Results are presented in nondimensional form which will greatly facilitate their use in the design of spherical shells containing a rigid or an elastic inclusion.


The freedom of fast iterations of distributed deep learning tasks is crucial for smaller companies to gain competitive advantages and market shares from big tech giants. HorovodRunner brings this process to relatively accessible spark clusters. There have been, however, no benchmark tests on HorovodRunner per se, nor specifically graph convolutional network (GCN, hereafter), and very limited scalability benchmark tests on Horovod, the predecessor requiring custom built GPU clusters. For the first time, we show that Databricks' HorovodRunner achieves significant lift in scaling efficiency for the convolutional neural network (CNN, hereafter) based tasks on both GPU and CPU clusters, but not the original GCN task. We also implemented the Rectified Adam optimizer for the first time in HorovodRunner.


EMFET is an open source and flexible tool that can be used to extract a large number of features from any email corpus with emails saved in EML format. The extracted features can be categorized into three main groups: header features, payload (body) features, and attachment features. The purpose of the tool is to help practitioners and researchers to build datasets that can be used for training machine learning models for spam detection. So far, 140 features can be extracted using EMFET. EMFET is extensible and easy to use. The source code of EMFET is publicly available at GitHub (this https URL)


Developing expertise in physics entails learning to use mathematics effectively and efficiently as applied to the context of physical situations. Doing so involves coordinating a variety of concepts and skills including mathematical processing, computation, blending ancillary information with the math, and reading out physical implications from the math and vice versa. From videotaped observations of intermediate level students solving problems in groups, we note that students often "get stuck" using a limited group of skills or reasoning and fail to notice that a different set of tools (which they possess and know how to use effectively) could quickly and easily solve their problem. We refer to a student's perception/judgment of the kind of knowledge that is appropriate to bring to bear in a particular situation as epistemic framing. Although epistemic framing is often unstated (and even unconscious), in group problem solving situations students sometimes get into disagreements about how to progress. During these disagreements, they bring forth explicit reasons or warrants in support of their point of view. For the context of mathematics use in physics problem solving, we present a system for classifying physics students' warrants. This warrant analysis offers tangible evidence of their epistemic framing.


PURPOSE
The presentation aims at illustrating the draft proposal of personal factors of the ICF for German-speaking regions which has been published in 2010 by the working group ICF of Faculty II "Social Medicine and Rehabilitation" of the German Society for Social Medicine and Prevention, DGSMP. For this reason, each personal factor is illustrated by two examples. Thus, the benefit is intended to be convincing.

METHODS
Applying a qualitative approach, the working group ICF consisting of members of various professions and institutions including a patients' representative selected for each item one example the factor serving as a facilitator and a second the factor serving as a barrier.

RESULTS
The components of the personal factors, as proposed, are presented, each factor is accompanied by two examples.

CONCLUSION
The presentation demonstrates the various possibilities of applying personal factors and intends to prove that the selection of items chosen makes sense. The process of a comprehensive discussion about the possible format of the component of personal factors in the ICF should lead to a further optimization of the proposal and the preparation of a discussion at an international level.


Prefabricated forms of construction have led to the rapid onsite assembly of buildings however there are still on-site tasks and processes which can be reevaluated and redone specifically in keeping with the principles of prefabrication instead being adapted to fit its purpose. One such process is that of waterproofing between prefabricated panels and modules which come from the factory fully complete façade and all. Conventional means of waterproofing can be used however it results in more work done on site, potential delays and generally requires access from the external face of the building. This paper presents the Modelling, Implementation and Evaluation of purpose developed weatherproof seals specific for Prefabricated Construction. An overview is provided of the entire development process and specific focus is given to the modeling using FEA computer simulations, manufacturing and testing which then resulted in the implementation in a prefabricated panelised building which is used as a case study and the means of further evaluation. These strategies have enabled an efficient and robust prefabricated waterproofing solution specific for this form of construction to be understood and implemented. The resulting case study has successfully verified the time and cost savings when compared to conventional techniques whilst still providing a durable and effective weatherproof seal for prefabricated panelised and modular systems.


Colorectal cancer (CRC) ranks third in incidence and second in mortality of all cancers worldwide. At the time of primary diagnosis, around 20% of patients already have metastatic CRC and only around 20% are candidates for radical resection. Thus, most of the patients have to undergo chemotherapy (CTx). Due to chemoresistance and side effects, novel treatment additives are crucial for controlling the disease and prolonging patient survival. The aim of this study was to evaluate probiotic supplementation and its antitumorigenic effects in an experimental CRC liver metastasis model. Six-week-old male Wistar rats received either a multispecies probiotic (1.2 × 109 CFU/daily) or placebo mixture. On day 14 of the experiment, rat CRC cells (CC531) were implanted under the liver capsule later treated by FOLFOX CTx. Change in tumor volume was measured by performing micro computed tomography (micro-CT) scanning on experimental days 28 and 34. Additionally, immunohistochemical staining with anti-MPO, anti-Ki67, and anti-CD31 were performed. Tumor apoptosis was evaluated using TUNEL staining. Micro-CT image analysis indicates that probiotic supplementation significantly inhibits tumor growth. No synergistic effects between probiotic supplementation and FOLFOX CTx was observed. Reduced tumor volume was achieved by inhibiting angiogenesis, as tumor microvascular density was significantly lower in rats receiving probiotic supplementation. This study shows that a multispecies probiotic mixture significantly reduces angiogenesis and inhibits CRC liver metastasis growth in an experimental rat model.


The Distributed Constraint Optimization Problem (DCOP) is a fundamental formalism for multi-agent cooperation. A dedicated framework called Resource Constrained DCOP (RCDCOP) has recently been proposed. RCDCOP models objective functions and resource constraints separately. A resource constraint is an n-ary constraint that represents the limit on the number of resources of a given type available to agents. Previous research addressing RCDCOPs employs the Adopt algorithm, which is a basic solver for DCOPs. In this paper we propose another version of the Adopt algorithm for RCDCOP using a pseudo-tree that is generated ignoring resource constraints. The key ideas of our work are as follows: (i) The pseudo-tree is generated ignoring resource constraints. (ii) Virtual variables are introduced, representing the usage of resources. These virtual variables are used to share resources among sub-trees. These ideas are used to extend Adopt. The proposed method reduces the previous limitations in the construction of RCDCOP pseudo-trees. The efficiency of our technique depends on the class of problems being considered, and we describe the obtained experimental results.


The automotive sector is one of the main pillars of the Brazilian industry and supplier companies – although often neglected in the literature have a crucial role in its growth. In these companies, processes associated with product development have increasing importance due to shorter products' life cycles and the continuous spillover of R&D activities to emergent countries, as observed in last decades. This study aims at proposing a managerial tool to support the business process of a plastics company, focused on activities triggered by the Request For Quotation (RFQ of "buy" non-Codesign parts, often sent by a car manufacturer) till the formal response to the client and the project planning. To achieve this objective, a search on the product development literature nurtured the contours of a first version of the proposal. Then, data about the quotation processes of two other automotive suppliers was collected in order to allow a comparative study. Finally, structured interviews were conducted with some managers of the plastics company to refine the understanding about the information flow and generate a final version of the proposed process and tool. As a result, a new process was designed as so as a new managerial tool to support its systematic application within the company. Such a proposal intends to guide the assignment of responsibilities among the functional areas, define clear inputs and outputs for each task and also assure that precise information can be generated for each involved agent throughout the quotation process and project planning. As a conclusion, not just the risk associated with the quotation process is expected to reduce, but also the horizontal communication and reliance among all internal functions involved is expected to improve. The experience described in this study also intends to serve as a reference for other non-codesign supplier companies in their challenge of establishing processes that enable a better insertion in the automotive supply chain and in its inter-organizational product development processes.


The main problems in the area studied were the irreversible drying and shrinkage of the soils. Factors of importance in this process were defined. To trace such factors the origin of pure peats and of mixtures of peat and clays was considered. Ways were suggested of preventing drying out and soil shrinkage.


The thermal conductivity of single-wall carbon nanotubes (SWCNTs) is predicted to increase with length, but this has never been proved experimentally because of limitations in previous measurement methods. Here, the authors report the measurement of the length-dependent thermal conductivities of individual SWCNTs on a Si substrate using a four-pad 3 omega method. An increase in thermal conductivity with length was observed at room temperature, which is consistent with a theoretical prediction that considers higher order three-phonon processes. When SWCNTs are longer than the phonon mean path, they showed dissipative thermal transport. The observed increase of thermal conductivity with length makes SWCNTs ideal for thermal management.(c) 2007 American Institute of Physics.


The aim of this research is to improve the conceptual understanding ability of student through problem based learning model was done in Mts. Al-Washliyah Tembung. The type of this research is Classroom Action Research. The research has done respect to the student of VIII-1 in number 40 students.
Instrument used to collect the data is conceptual understanding mathematics test and observation sheet. These researches consist of two cycles and the end of every cycle given conceptual understanding mathematics test. Before given, at the first test must be validity. Validity test done is contents validity where expert as validator.
The result in this research has shown that learning by problem based learning model can improve the conceptual understanding mathematics. From initial test that given to student said that student has good ability in prerequisite material. It indicate from the average value of initial test of 40 student is 82.50. This case shown from the result before treatment, in first conceptual understanding test I of 40 students there are 18 students (45%) gained the score  70 with the average class is 48.25.
After given treatment so the students do the conceptual understanding test II of 40 students there are 35 students (87.5%) gained the score  70 with the average class is 82.25. The observation sheet get average score 2.735 in cycle 1, its in good category. In cycle 2 get average score 3.365, it indicate teacher is very good category in implement problem based learning in classroom.
From the result of research can conclude that by implementation problem based learning model can improve the conceptual understanding of student. Mathematics teacher of Mts. Al-Washliyah Tembung suggested can implement problem based learning model in improving conceptual understanding of student. To students suggested more active to found the concept of mathematics.


We introduce temporally and contextually-aware models for the novel task of predicting unseen but plausible concepts, as conveyed by noun-noun compounds in a time-stamped corpus. We train compositional models on observed compounds, more specifically the composed distributed representations of their constituents across a time-stamped corpus, while giving it corrupted instances (where head or modifier are replaced by a random constituent) as negative evidence. The model captures generalisations over this data and learns what combinations give rise to plausible compounds and which ones do not. After training, we query the model for the plausibility of automatically generated novel combinations and verify whether the classifications are accurate. For our best model, we find that in around 85% of the cases, the novel compounds generated are attested in previously unseen data. An additional estimated 5% are plausible despite not being attested in the recent corpus, based on judgments from independent human raters.


Rationale Human coronaviruses (HCoVs) seriously affect human health by causing respiratory diseases ranging from common colds to severe acute respiratory diseases. Immunophilins, including peptidyl-prolyl isomerases of the FK506-binding protein (FKBP) and the cyclophilin family, are promising targets for pharmaceutical inhibition of coronavirus replication, but cell-type specific effects have not been elucidated. FKBPs and cyclophilins bind the immunosuppressive drugs FK506 and cyclosporine A (CsA), respectively. Methods Primary human bronchial epithelial cells (phBECs) were treated with CsA, Alisporivir (ALV), FK506, and FK506-derived non-immunosuppressive analogs and infected with HCoV-229E. RNA and protein were assessed by RT-qPCR and immunoblot analysis. Treatment with the same compounds was performed in hepatoma cells (Huh-7.5) infected with HCoV-229E expressing Renilla luciferase (HCoV-229E-RLuc) and the kidney cell line HEK293 transfected with a SARS-CoV-1 replicon expressing Renilla luciferase (SARS-CoV-1-RLuc), followed by quantification of luminescence as a measure of viral replication. Results Both CsA and ALV robustly inhibited viral replication in all models; both compounds decreased HCoV-229E RNA in phBECs and reduced luminescence in HCoV-229E-RLuc-infected Huh7.5 and SARS-CoV-1-RLuc replicon-transfected HEK293. In contrast, FK506 showed inconsistent and less pronounced effects in phBECs while strongly affecting coronavirus replication in Huh-7.5 and HEK293. Two non-immunosuppressive FK506 analogs had no antiviral effect in any infection model. Conclusion The immunophilin inhibitors CsA and ALV display robust anti-coronaviral properties in multiple infection models, including phBECs, reflecting a primary site of HCoV infection. In contrast, FK506 displayed cell-type specific effects, strongly affecting CoV replication in Huh7.5 and HEK293, but inconsistently and less pronounced in phBECs.


The effects of a highly selective Na+/H+ exchange inhibitor cariporide on the reperfused in situ heart were assessed. Male Sprague-Dawley (SD) rats weighing 200-300 g were anesthetized with pentobarbital sodium (60 mg/kg, i.p.) and divided into four groups; sham-operated (n = 6), vehicle (n = 15), 0.1 mg/kg (n = 15), and 1.0 mg/kg (n = 15) groups. The left coronary artery was ligated for 5 min and then released with ECG and blood pressure monitoring. Cariporide was intravenously given as a bolus 2 min before the reperfusion. The heart was rapidly excised and frozen 3 min after the onset of ventricular fibrillation, otherwise 10 min after the reperfusion. The adenosine triphosphate (ATP), creatine phosphate (CP), and glycogen contents were measured in the reperfused ischemic myocardium by using an enzymatic fluorometric assay technique. The incidence of the lethal ventricular fibrillation was 53% in the vehicle, 27% in the low-dose and 7% in the high-dose group. The concentrations (mean+/-SEM) of ATP, CP (nmol/mg protein), and glycogen (nmol as glucose/mg protein) were 74+/-4, 255+/-19, and 164+/-21 in the sham, 23+/-4, 763+/-70, and 61+/-7 in the vehicle, 27+/-4, 180+/-16, and 104+/-14 in the low-dose, and 32+/-4, 178+/-24, and 108+/-8 in the high-dose groups, respectively, indicating that cariporide significantly blunted CP overshoot as well as glycogenolysis during reperfusion. Thus cariporide can be expected to depress arrhythmogenesis and protect the metabolic status of the heart.


methods of diagnosis, treatment, and prevention, which are also considered in the earlier chapters. As a synopsis of parasitology, this book is useful, and its 12 tables and 34 line drawings are clear and precise; as a guide to the action of drugs on parasites, it is much less valuable, and one looks in vain for information regarding the nature of the antimalarial or anthelminthic activity of the new synthetic compounds.


The ever-increasing urbanisation and deforestation in the metropolises of the Eastern region has led to the loss of a great diversity of fruit and even forest species. In view of this difficulty, a study was carried out on diversity of fruit species and production contraints in home gardens in the metropolises of Eastern region of Cameroon. The methodological approach involved snowball sampling through the administration of a semi-structured questionnaire to 189 home gardens in the districts of Mandjou, Bertoua II and Batouri. The results showed a diversity of 15 fruit species corresponding to an abundance of 4126 individuals. The mandarin tree is the most cultivated species (1153 trees). Young trees (<10) are in the majority in Bertoua (55,3%) and Mandjou (60,5%). Seeds are mainly sourced from local markets (73%) and trees maintenance is almost non-existent (86,4%). The most important production contraint is low production (41,6%). This study highlighted the diversity of fruit species and production contraints in home gardens in the East Cameroon region.
Key words : Diversity, fruit species, production contraints, home gardens.