Miracle-dz/UniFAR-FTUs huggingface dataset:
Proapoptotic Effect on Normal and Tumor Intestinal Cells of Cytostatic Drugs with Enterohepatic Organotropism

The proapoptotic effect of cisplatin bile acid derivatives Bamet-R2 [cis-diamminechloro-cholylglycinate-platinum(II)] and Bamet-UD2 [cis-diammine-bisursodeoxycholate-platinum(II)], developed to treat liver and intestinal tumors, was investigated in vitro using human enterohepatic cells HepG2 (hepatoblastoma), LS 174T (colon adenocarcinoma), and its cisplatin-resistant subline LS 174T/R. Uptake by wild-type tumor cells was higher for Bamets than for cisplatin. In LS 174T/R cells, copper transporter-1 was down-regulated and multidrug resistance-associated protein-2 was up-regulated. Consequently, uptake and efflux of cisplatin, but not those of Bamets, were reduced and increased, respectively. The degree of necrosis (lactate dehydrogenase release) induced by these three drugs was small and similar in all cell types. In contrast, proapoptotic effect (caspase-3 activity and DNA fragmentation) was Bamet-UD2 > cisplatin > Bamet-R2 in HepG2 and LS 174T cells, but Bamet-UD2 > Bamet-R2 >> cisplatin in LS 174T/R cells. This effect was consistent with the ability of these compounds to form DNA-adducts (DNA-platination, changes in the DNA melting temperature, and MspI-induced restriction sequence cleavage). Oral administration of Bamet-UD2 to mice induced mild apoptosis in the small intestine (ileum > duodenum), which was not severe enough to modify its structure or function as determined by water absorption and glycocholic acid uptake by in situ perfused ileum. These results indicate that Bamet-UD2 overcomes the resistance to cisplatin when this is due in part to enhanced ability of intestinal tumors to reduce intracellular cisplatin contents. Moreover, its strong proapoptotic versus its weak pronecrotic effect together with its mild effect on normal tissues, including intestinal mucosa, may account for the high antitumor activity of Bamet-UD2 together with its very low toxicity.
"I check my emails on the toilet": Email Practices and Work-Home Boundary Management

Email is widely used as a means of communication, a task management system and an archive and it often seems impossible to live without it. Our always-online society expects us to be available 24/7 at the cost of potentially blurring the boundaries between work and personal life. Furthermore, mobile and handheld devices have made it even easier to be connected and therefore increased the sense of needing to be available to respond at any time. Whilst research to date has focused on identifying email practices on the desktop, little has been done to understand whether and how the introduction of mobile devices has changed our way of handling emails. In this paper, we describe preliminary results from an interview study that explored in particular the role of mobile devices in email management and work-home boundary management. We found that mobile technology impacts even on the most private of non-work moments. We provide examples of the ways in which technology supports frequent switching between work and non-work contexts, and demonstrate the strategies that people develop in order to manage these boundaries, by using what we call micro-boundaries (e.g. having two email apps on a phone).
Emission of particulate matter from a desktop three-dimensional (3D) printer

ABSTRACT Desktop three-dimensional (3D) printers are becoming commonplace in business offices, public libraries, university labs and classrooms, and even private homes; however, these settings are generally not designed for exposure control. Prior experience with a variety of office equipment devices such as laser printers that emit ultrafine particles (UFP) suggests the need to characterize 3D printer emissions to enable reliable risk assessment. The aim of this study was to examine factors that influence particulate emissions from 3D printers and characterize their physical properties to inform risk assessment. Emissions were evaluated in a 0.5-m3 chamber and in a small room (32.7 m3) using real-time instrumentation to measure particle number, size distribution, mass, and surface area. Factors evaluated included filament composition and color, as well as the manufacturer-provided printer emissions control technologies while printing an object. Filament type significantly influenced emissions, with acrylonitrile butadiene styrene (ABS) emitting larger particles than polylactic acid (PLA), which may have been the result of agglomeration. Geometric mean particle sizes and total particle (TP) number and mass emissions differed significantly among colors of a given filament type. Use of a cover on the printer reduced TP emissions by a factor of 2. Lung deposition calculations indicated a threefold higher PLA particle deposition in alveoli compared to ABS. Desktop 3D printers emit high levels of UFP, which are released into indoor environments where adequate ventilation may not be present to control emissions. Emissions in nonindustrial settings need to be reduced through the use of a hierarchy of controls, beginning with device design, followed by engineering controls (ventilation) and administrative controls such as choice of filament composition and color.
Efficient diagnosable design of the IEEE P1500 architecture for SoC testing

System-on-a-chip (SoC) as a platform for system integration has been used extensively in modern VLSI design. The IEEE P1500 has been proposed as a standard for the challenging SoC testing problem. In order to improve the correctness of SoC testing, the IEEE P1500 hardware itself should be tested and diagnosed first before using it. This paper proposes an efficient design-for-diagnosability architecture for the IEEE P1500 and evaluates its performance. Effective diagnosis procedures are presented and the response sequences of the output are analyzed for fault diagnosis. With our proposed designs, single stuck-at faults and fault location can be efficiently determined.
A Study of the Effect of Reward systemâs Mechanisms on New Product development considering the mediating role of Knowledge-Sharing (Case study: Home Appliances Province Manufacturing Companies in Esfahan)

The present paper, titled ‘A Study of the Effect of reward systemʼs mechanisms on new product development the mediating role of knowledge-sharing’ examines the important role of rewarding mechanisms in facilitating the knowledge-sharing among individuals and the effects of a joint reward system on knowledge-sharing among the members and the new product development performance in home appliances factories in Isfahan Province. This research, in terms of its purpose, is an applied one; and in terms of implementation method, is a survey with a correlation approach. The statistical population include 170 managers (senior, marketing, manufacturing and R&D) of the home appliances manufacturing companies in Esfahan Province. Since the population is limited no sampling is necessary. Thus, the whole population is studied. The data collection tool is a researcher-made questionnaire containing 30 items, of which the validity has been confirmed using the comments from advisors, professionals and experts; and the reliability, determined through Cronbach's alpha coefficient of 92%) The questionnaire includes personal data and main, specialized items for examining the research hypotheses. The collected data were analyzed using SPSS and AMOS software programs through statistical tests at descriptive (frequency, percentage, accumulated percentage, average and standard deviation) and inferential (t-test, regression modeling, variance analysis, nonparametric Kolmogorov and Smirnov test, and Freedman nonparametric test) levels. According to the results obtained, all hypotheses were supported. 1. Corresponding Author: M.S.C. , Business management, Islamic Azad University, Branch of Mobarakeh, Iran. tanialadoni@yahoo.com International Journal of Academic Research in Business and Social Sciences November 2013, Vol. 3, No. 11 ISSN: 2222-6990 155 www.hrmars. com/journals Therefore, it was concluded that joint design of reward system has a significant effect on the development of a new product.
Validation of Two-Sample Bootstrap in ROC Analysis on Large Datasets Using AURC | NIST

– Sampling variability results in uncertainties of measures. The nonparametric two-sample bootstrap method has been used to compute uncertainties of measures in receiver operating characteristic (ROC) analysis on large datasets, such as the standard error (SE) of the equal error rate in biometrics, the SE of a detection cost function in speaker recognition evaluation, and others. Specifically, the SE of the area under ROC curve (AURC) can be computed analytically using the Mann-Whitney statistic. It can also be calculated using the nonparametric two-sample bootstrap method. The analytical result could be treated as a ground truth. The relative errors of bootstrap-method results with respect to the analytical-method results using different matching algorithms were examined, and they were quite small. Hence, this validates the nonparametric two-sample bootstrap method applied in ROC analysis on large datasets.
Subequivalence Relations and Positive-Definite Functions

We study a positive-definite function associated to a measure-preserving equivalence relation on a standard probability space and use it to measure quantitatively the proximity of subequivalence relations. This is combined with a recent co-inducing construction of Epstein to produce new kinds of mixing actions of an arbitrary infinite discrete group and it is also used to show that orbit equivalence of free, measure preserving, mixing actions of non-amenable groups is unclassifiable in a strong sense. Finally, in the case of property (T) groups we discuss connections with invariant percolation on Cayley graphs and the calculation of costs.
Saxagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus

Introduction: The worldwide prevalence of type 2 diabetes mellitus (T2DM) is high, and the chronically poor metabolic control that can result from T2DM is associated with a high risk for microvascular and macrovascular complications. Because of the progressive pathophysiology of T2DM, oral antidiabetic agents often fail to provide sustained glycemic control, indicating the need for new therapies. Saxagliptin (Onglyza™; Bristol-Myers Squibb Company, Princeton, NJ, USA; AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA) is an oral dipeptidyl peptidase-4 inhibitor, recently approved for the treatment of T2DM. Evidence review: Saxagliptin significantly improves glycemic control vs placebo, as demonstrated by decreasing glycated hemoglobin, fasting plasma glucose, and postprandial plasma glucose levels when used as monotherapy; in initial combination with metformin; and as add-on therapy with metformin, sulfonylurea (SU), or thiazolidinedione (TZD). Saxagliptin also significantly improves β-cell function, is weight neutral, has a low risk for hypoglycemia, and has been shown to have cardiovascular safety. Place in therapy: The clinical profile for saxagliptin indicates that it is useful as an adjunct to diet and exercise as first-line monotherapy and in combination with metformin; or as add-on treatment for patients who cannot achieve glycemic control with a combination of diet and lifestyle changes and metformin, SU, or TZD.
The Profile of Academic Offenders: Features of Students Who Admit to Academic Dishonesty

Dishonesty in academic settings is a reckless behavior that is unique to students and is associated with cheat ing and plagiarism of academic tasks. Incidents involving dishonesty in higher education have increased considerably in the past decade, with regard to the extent of these practices, the types of dishonesty employed, and their prevalence. The current study examines the profile of “academic offenders”. Which types are more prone to commit academic offenses? To what degree are they “normative” and do they represent the average student with regard to personal traits, personal perceptions, features of their academic studies, risk behaviors, and health risks. The study is based on a structured anonymous questionnaire. The sample consisted of 1,432 students, of whom 899 were female (63%) and 533 male (37%). The research findings indicate a common tendency among more than one quarter of the sample reported cheating on homework and 12.5% reported cheating on tests. Strong associations were found between academic dishonesty and various personal perceptions, the academic study experience, and involvement in other risky and deviant behaviors. Significant predictors of academic dishonesty were found, i.e., self-image, ethics, grades, time devoted to homework, and deviant and daring behaviors. The research findings might help indicate policies for optimally dealing with dishonesty, maybe even before the offense is committed, by means of cooperation between academic forces.
Predictive Approaches For Gaussian Process Classifier Model Selection

In this paper we consider the problem of Gaussian process classifier (GPC) model selection with different Leave-One-Out (LOO) Cross Validation (CV) based optimization criteria and provide a practical algorithm using LOO predictive distributions with such criteria to select hyperparameters. Apart from the standard average negative logarithm of predictive probability (NLP), we also consider smoothed versions of criteria such as F-measure and Weighted Error Rate (WER), which are useful for handling imbalanced data. Unlike the regression case, LOO predictive distributions for the classifier case are intractable. We use approximate LOO predictive distributions arrived from Expectation Propagation (EP) approximation. We conduct experiments on several real world benchmark datasets. When the NLP criterion is used for optimizing the hyperparameters, the predictive approaches show better or comparable NLP generalization performance with existing GPC approaches. On the other hand, when the F-measure criterion is used, the F-measure generalization performance improves significantly on several datasets. Overall, the EP-based predictive algorithm comes out as an excellent choice for GP classifier model selection with different optimization criteria.
Population, Unemployment and Economic Growth Cycles: A Further Explanatory Perspective

In this paper we investigate the dynamic interaction between economic growth, unemployment, income distribution and population growth. The reference framework combines rational behaviour of agents with endogenous fertility and unemployment, while profits are the determinant of the accumulation of firms. In particular the supply of labour is determined by the micro-founded fertility choices of individuals. We first demonstrate, consistently with the empirical evidence, the existence of a positive income growth trend with sustained oscillations, therefore providing an alternative explanation of the relation between growth and cycle. Moreover interesting results are given on the relation between unemployment and growth. So far the literature has traditionally shown a negative relation between unemployment and growth (with the exception of the positive relation arising in a Schumpeter 'creative' disruption context). In contrast, we find a twofold effect of unemployment (via its effects on population) on economic growth: this can be both positive or negative depending on the relative level of the cost of childrearing of employed and unemployed persons, and on the level of unemployment benefits. This allows us to argue that an increase in unemployment benefit-as has occurred in recent years in many countries such as France and Spain-could lead to wide demo-economic fluctuations and to a positive effect of unemployment on economic growth. Copyright Blackwell Publishing Ltd 2003.
MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model

Fibrosis of organs is observed in systemic autoimmune disease. Using a scleroderma mouse, we show that transplantation of MHC compatible, minor antigen mismatched bone marrow stromal/stem cells (BMSCs) play a role in the pathogenesis of fibrosis. Removal of donor BMSCs rescued mice from disease. Freshly isolated PDGFRα+ Sca-1+ BMSCs expressed MHC class II following transplantation and activated host T cells. A decrease in FOXP3+ CD25+ Treg population was observed. T cells proliferated and secreted IL-6 when stimulated with mismatched BMSCs in vitro. Donor T cells were not involved in fibrosis because transplanting T cell-deficient RAG2 knock out mice bone marrow still caused disease. Once initially triggered by mismatched BMSCs, the autoimmune phenotype was not donor BMSC dependent as the phenotype was observed after effector T cells were adoptively transferred into naïve syngeneic mice. Our data suggest that minor antigen mismatched BMSCs trigger systemic fibrosis in this autoimmune scleroderma model. DOI: http://dx.doi. org/10.7554/eLife.09394. 001
Adapting a Database of Text Messages to a Mobile-Based Weight Loss Program: The Case of the Middle East

Obesity has become a worldwide epidemic. Qatar, a rapidly developing country in the Middle East, has seen a sharp increase in the prevalence of obesity. The increase can be attributed to several reasons, including sedentary lifestyles imposed by a harsh climate and the introduction of Western fast food. Mobile technologies have been used and studied as a technology to support individuals' weight loss. The authors have developed a mobile application that implements three strategies drawn from proven theories of behavioral change. The application is localized to the cultural context of its proposed users. The objective of this paper is to present a method through which we adapted the messaging content of a weight loss application to the context of its users while retaining an effective degree of automation. The adaptation addressed body image, eating and physical exercise habits, and regional/cultural needs. The paper discusses how surveying potential users can be used to build a profile of a target population, find common patterns, and then develop a database of text messages. The text messages are automated and sent to the users at specific times of day, as suggested by the survey results.
Cellular Proteins PML and Daxx Mediate an Innate Antiviral Defense Antagonized by the Adenovirus E4 ORF3 Protein

ABSTRACT The adenovirus (Ad) E4 ORF3 protein is both necessary and sufficient to reorganize a nuclear subdomain, the PML nuclear body (PML-NB), from punctate structures into elongated nuclear tracks. PML-NB disruption is recapitulated by a variety of DNA viruses that encode proteins responsible for compromising PML-NB integrity through different mechanisms. PML-NB disruption has been correlated with the antagonism of both innate and intrinsic immune responses. The E4 ORF3 protein is required for adenoviral DNA replication in the interferon (IFN)-induced antiviral state. This may reflect the fact that PML itself, in addition to several other PML-NB proteins, is encoded by an interferon-stimulated gene. Here, we demonstrate that reorganization of the PML-NB by E4 ORF3 antagonizes an innate antiviral response mediated by both PML and Daxx. Reduction of either of these proteins is sufficient to restore the replicative capacity of virus with the E4 ORF3 protein deleted in the IFN-induced antiviral state. Further, we provide evidence that both the HSV1 ICP0 and HCMV IE1 proteins, which disrupt PML-NBs by mechanistically distinct strategies, behave in a manner functionally analogous to E4 ORF3 with respect to antagonizing the IFN-induced antiviral state. In addition, we assert that this innate antiviral strategy mediated by PML and Daxx does not involve transcriptional repression. While early gene transcription is modestly diminished in the absence of E4 ORF3 protein expression, this reduction does not affect early protein function. We propose that, in addition to its ability to repress gene expression, the PML-NB participates in additional innate immune activities.
Superior Control of HIV-1 Replication by CD8+ T Cells Targeting Conserved Epitopes: Implications for HIV Vaccine Design

A successful HIV vaccine will likely induce both humoral and cell-mediated immunity, however, the enormous diversity of HIV has hampered the development of a vaccine that effectively elicits both arms of the adaptive immune response. To tackle the problem of viral diversity, T cell-based vaccine approaches have focused on two main strategies (i) increasing the breadth of vaccine-induced responses or (ii) increasing vaccine-induced responses targeting only conserved regions of the virus. The relative extent to which set-point viremia is impacted by epitope-conservation of CD8+ T cell responses elicited during early HIV-infection is unknown but has important implications for vaccine design. To address this question, we comprehensively mapped HIV-1 CD8+ T cell epitope-specificities in 23 ART-naïve individuals during early infection and computed their conservation score (CS) by three different methods (prevalence, entropy and conseq) on clade-B and group-M sequence alignments. The majority of CD8+ T cell responses were directed against variable epitopes (p<0.01). Interestingly, increasing breadth of CD8+ T cell responses specifically recognizing conserved epitopes was associated with lower set-point viremia (r = - 0.65, p = 0.009). Moreover, subjects possessing CD8+ T cells recognizing at least one conserved epitope had 1.4 log10 lower set-point viremia compared to those recognizing only variable epitopes (p = 0.021). The association between viral control and the breadth of conserved CD8+ T cell responses may be influenced by the method of CS definition and sequences used to determine conservation levels. Strikingly, targeting variable versus conserved epitopes was independent of HLA type (p = 0.215). The associations with viral control were independent of functional avidity of CD8+ T cell responses elicited during early infection. Taken together, these data suggest that the next-generation of T-cell based HIV-1 vaccines should focus on strategies that can elicit CD8+ T cell responses to multiple conserved epitopes of HIV-1.
Signatures of Incomplete Paschen-Back Splitting in the Polarization Profiles of the He I λ10830 Multiplet

We investigate the formation of polarization profiles induced by a magnetic field in the He I multiplet at 10830 Å. Our analysis considers the Zeeman splitting in the incomplete Paschen-Back regime. The effects turn out to be important and produce measurable signatures on the profiles, even for fields significantly weaker than the level-crossing field (~400 G). When compared to profiles calculated with the usual linear Zeeman effect, the incomplete Paschen-Back profiles exhibit the following conspicuous differences: (1) a non-Doppler blueshift of the Stokes V zero-crossing wavelength of the blue component; (2) area and peak asymmetries, even in the absence of velocity and magnetic gradients; and (3) a ~25% reduction in the amplitude of the red component. These features do not vanish in the weak-field limit. The spectral signatures that we analyze in this paper may be found in previous observations published in the literature.
Catastrophic Mortality Bonds: Analysing Basis Risk and Hedge Effectiveness

Life insurers are exposed to catastrophic mortality risk. Catastrophic mortality bonds are a recent market innovation that provide an alternative risk management tool to address this risk. However there is little in the way of published studies that examines their effectiveness, given that they are subject to basis risk arising from the use of country-level general population mortality in their construction. By constructing a typical mortality risk portfolio and calibrating a bond for this portfolio, the hedge effectiveness of the instrument is analysed under a wide variety of circumstances. We find that, on a stand-alone basis, hedge effectiveness may be too low to be acceptable to small to medium insurers. However, effectiveness of the bond increases when used in combination with surplus reinsurance and/or when pooling is used to increase portfolio size.