Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Resistance Study of AG-021541, a Novel Nonnucleoside Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase

ABSTRACT A novel class of nonnucleoside hepatitis C virus (HCV) polymerase inhibitors characterized by a dihydropyrone core was identified by high-throughput screening. Crystallographic studies of these compounds in complex with the polymerase identified an allosteric binding site close to the junction of the thumb and finger domains, approximately 30 Å away from the catalytic center. AG-021541, a representative compound from this series, displayed measurable in vitro antiviral activity against the HCV genotype 1b subgenomic replicon with a mean 50% effective concentration of 2.9 μM. To identify mutations conferring in vitro resistance to AG-021541, resistance selection was carried out using HCV replicon cells either by serial passages in increasing concentrations of AG-021541 or by direct colony formation at fixed concentrations of the compound. We identified several amino acid substitutions in the AG-021541-binding region of the polymerase, including M423(T/V/I), M426T, I482(S/T), and V494A, with M423T as the predominant change observed. These mutants conferred various levels of resistance to AG-021541 and structurally related compounds but remained sensitive to interferon and HCV polymerase inhibitors known to interact with the active site or other allosteric sites of the protein. In addition, dihydropyrone polymerase inhibitors retained activity against replicons that contain signature resistance changes to other polymerase inhibitors, including S282T, C316N, M414T, and P495(S/L), indicating their potential to be used in combination therapies with these polymerase inhibitors. AG-021541-resistant replicon cell lines provide a valuable tool for mechanism-of-action studies of dihydropyrone polymerase inhibitors. The clinical relevance of in vitro resistance to HCV polymerase inhibitors remains to be investigated.
Graph-Based Semi-Supervised Learning and Spectral Kernel Design

In this paper, we consider a framework for semi-supervised learning using spectral decomposition-based unsupervised kernel design. We relate this approach to previously proposed semi-supervised learning methods on graphs. We examine various theoretical properties of such methods. In particular, we present learning bounds and derive optimal kernel representation by minimizing the bound. Based on the theoretical analysis, we are able to demonstrate why spectral kernel design based methods can improve the predictive performance. Empirical examples are included to illustrate the main consequences of our analysis.
Analytical Features: A Knowledge-Based Approach to Audio Feature Generation

We present a feature generation system designed to create audio features for supervised classification tasks. The main contribution to feature generation studies is the notion of analytical features (AFs), a construct designed to support the representation of knowledge about audio signal processing. We describe the most important aspects of AFs, in particular their dimensional type system, on which are based pattern-based random generators, heuristics, and rewriting rules. We show how AFs generalize or improve previous approaches used in feature generation. We report on several projects using AFs for difficult audio classification tasks, demonstrating their advantage over standard audio features. More generally, we propose analytical features as a paradigm to bring raw signals into the world of symbolic computation.
Engineering and Characterization of an Enhanced Fluorescent Protein Voltage Sensor

Background Fluorescent proteins have been used to generate a variety of biosensors to optically monitor biological phenomena in living cells. Among this class of genetically encoded biosensors, reporters for membrane potential have been a particular challenge. The use of presently known voltage sensor proteins is limited by incorrect subcellular localization and small or absent voltage responses in mammalian cells. Results Here we report on a fluorescent protein voltage sensor with superior targeting to the mammalian plasma membrane and high responsiveness to membrane potential signaling in excitable cells. Conclusions and Significance This biosensor, which we termed VSFP2.1, is likely to lead to new methods of monitoring electrically active cells with cell type specificity, non-invasively and in large numbers, simultaneously.
Speed cameras in an urban setting: a cost–benefit analysis

Background To perform a cost–benefit analysis of the installation of speed cameras on the beltways of Barcelona. Methods The analysis was performed from the society perspective over a 2-year period using a controlled before-and-after study design. The net benefit was calculated using, as benefits, the willingness to pay for the estimated number of people who avoided injury as a consequence of the intervention, subtracting costs and savings. Sensitivity analyses were performed using the maximum and minimum estimated number of people who avoided injury, assuming that there was a minimum of one death avoided, using the maximum value of a statistical life, assigning all implementation costs to the first year and assuming there was no time lost due to speed reduction. Results Base case results showed a net benefit of €6.8 million. Sensitivity analyses suggested that net benefits could range from €5.6 to €23.1 million over 2 years. Conclusions The use of speed cameras in urban areas has a favourable economic impact even when assessed using conservative assumptions.
Features of the interactions between a vacancy and interstitial loops in metals

Point defects and defect clusters have been observed in metals irradiated by high-energy particles. Interactions of these defects between themselves and with existing microstructure features cause microstructure evolution and lead to changes in mechanical and physical properties of the irradiated materials. Models for prediction of radiation-induced changes should include details of reactions involving defects, and so in this paper we present the results of atomic-scale computer modelling of interactions between a cluster of self-interstitial atoms (SIAs) and a single vacancy in models of bcc, fcc and hcp metals. The vacancy is taken to lie on or within the glide prism of the cluster. This type of reaction is considered to be one of the most frequent because formation of SIA clusters, particularly glissile clusters, is commonly observed in high-energy displacement cascades in all metals. The interaction depends strongly on the dislocation nature of the cluster and therefore these interactions are different in the three crystal structures. Vacancy–SIA recombination, in particular, is inhibited by dissociation of the SIA loop on its glide prism.
A Stakeholder Analysis for Telemedicine in China

Telemedicine is considered as one of the technological approaches that could alleviate the healthcare disparity in China and improve the accessibility, affordability and quality of health services. However, the success and diffusion rates of telemedicine keep at a very low level in China. While related technologies have been intensively studied and significantly improved, much fewer researches are directed to the social and organizational issues on telemedicine in the country. We employ the stakeholder theory to examine the key groups that have significant impacts on the implementation and operations of telemedicine so that management strategies can be developed to release the power of telemedicine as a new approach to healthcare delivery.
Infections After Kidney Transplantation: The Bug Bear Of Kidney Transplantation In Tropics

Infections are the bugbear of kidney transplantation in the tropics, being responsible for majority of the deaths. Despite the several challenges posed by infections in kidney transplant recipient in the tropics, various developments have resulted in a decline in the rate of infections as well as their consequences. This review aims to be a basic overview of the common infections in KTR with an attempt to provide a unique tropical country perspective.
Application properties of TCP/OMMT flame-retardant system in NR composites

Due to high flammability setback of most natural and synthetic rubbers, a novel organic/inorganic hybrid flame-retardant additive by the combination of tricresyl phosphate (TCP) and organomontmorillonite (OMMT) was prepared and used in the preparation of flame-retardant rubber composites. Different types of natural rubber (NR)/TCP/OMMT composites were prepared with different amounts of this novel additive. Then, the main properties were researched and compared with the composites directly incorporated with TCP or OMMT. The tensile strength and elongation at break of NR/TCP-10/OMMT-5 were 15.5 MPa and 673%, respectively, which increased about 10% and 16% compared with that of NR/TCP-10 composite. Meanwhile, the abrasion loss of NR/TCP-10/OMMT-5 was 0.49 cm3, decreased by 26% in comparison with that of NR/OMMT-5 composite, that is, to 0.62 cm3. Moreover, the limiting oxygen index value was increased to about 34.0% and the thermal stability of which was also improved with the addition of 10 parts per hundreds of rubber of TCP and OMMT into NR systems. In addition, the plausible mechanism for the improvement of reinforcing, wear resistant, and flame-retardant properties were put forward.
Electrochemical Impedance Spectroscopy Of Epoxy-Coated Steel Exposed To Dead Sea Water

Electrochemical impedance tests were applied to steel specimens which were coated by epoxy and tested after immersion in Dead Sea water for different periods at room temperature and at 50C. Results taken from Nyquist and Bode plots and as were analyzed by means of software provided with the instrument. Results were presented as the values of capacitance and resistance (Cdl and Rct). Results show that degradation occurred after immersion in the test solution, and were more severe at higher temperature. Specimens were examined under scanning electron microscope, and micrographs showed clear rupture and degradation in epoxy coatings.
Approximating bounded, nonorientable surfaces from points

We present an approach to surface approximation from points that allows reconstructing surfaces with boundaries, including globally nonorientable surfaces. The surface is defined implicitly using directions of weighted covariances and weighted averages of the points. Specifically, a point belongs to the surface, if its direction to the weighted average has no component into the direction of smallest covariance. For bounded surfaces, we require in addition that any point on the surface is close to the weighted average of the input points. We compare this definition to alternatives and discuss the details and parameter choices. Points on the surface can be determined by intersection computations. We show that the computation is local and, therefore, no globally consistent orientation of normals is needed. Continuity of the surfaces is not affected by the particular choice of local orientation. We demonstrate our approach by rendering several bounded (and nonorientable) surfaces using ray casting.
Revisiting financial conflicts of interest in FDA advisory committees.

CONTEXT The Food and Drug Administration (FDA) Safety and Innovation Act has recently relaxed conflict-of-interest rules for FDA advisory committee members, but concerns remain about the influence of members' financial relationships on the FDA's drug approval process. Using a large newly available data set, this study carefully examined the relationship between the financial interests of FDA Center for Drug Evaluation and Research (CDER) advisory committee members and whether members voted in a way favorable to these interests. METHODS The study used a data set of voting behavior and reported financial interests of 1,379 FDA advisory committee members who voted in CDER committee meetings that were convened during the 15-year period of 1997-2011. Data on 1,168 questions and 15,739 question-votes from 379 meetings were used in the analyses. Multivariable logit models were used to estimate the relationship between committee members' financial interests and their voting behavior. FINDINGS Individuals with financial interests solely in the sponsoring firm were more likely to vote in favor of the sponsor than members with no financial ties (OR = 1.49, p = 0.03). Members with interests in both the sponsoring firm and its competitors were no more likely to vote in favor of the sponsor than those with no financial ties to any potentially affected firm (OR = 1.16, p = 0.48). Members who served on advisory boards solely for the sponsor were significantly more likely to vote in favor of the sponsor (OR = 4.97, p = 0.005). CONCLUSIONS There appears to be a pro-sponsor voting bias among advisory committee members who have exclusive financial relationships with the sponsoring firm but not among members who have nonexclusive financial relationships (ie, those with ties to both the sponsor and its competitors). These findings point to important heterogeneities in financial ties and suggest that policymakers will need to be nuanced in their management of financial relationships of FDA advisory committee members.
Aging, nutrition and immunity – their relationship and interaction

Demographic shifts worldwide are resulting in ever-increasing numbers of the elderly in both developed and developing countries. With aging come changes in physical and physiological integrity that are accompanied by a gradual decline in immunocompetence, commonly termed 'immunosenescence'. Indeed, there are marked differences between young and old subjects with respect to the proportions of naand memory T cells and less marked differences in B cells and other immune cells. The number and proportion of late-stage memory T and B cells commonly increases, being particularly prominent in the CD8+ cytotoxic T cell pool. The accumulation of late-stage potentially "terminally" differentiated CD8+CD27−CD28−CD45RA+ cells is often considered a hallmark of immunosenescence. Malnutrition in old age can further add to the severity of this age-associated remodeling of the immune system. Age-associated obesity, in particular, is accompanied by greater chronic inflammation, as reflected in increased plasma concentrations of C-reactive protein (CRP), IL-6, TNF and other factors which may mark compromised immunity. These physiological and immunological changes accompanying aging, markedly affected by nutritional status, are likely to be different in different parts of the globe. Data suggest a gradual decline in both nutritional status and immune functions with aging, but the details of these processes, and potential differences in different societies are unclear. In the following review, we will discuss the hallmarks of age-associated immune system changes and consider how these might be affected by nutritional status.
Thermal laser attack and high temperature heating on HfO2-based OxRAM cells

The last 10 years have seen the rise of new NVM technologies as alternative solutions to Flash technology, which is facing downsizing issues. Apart from offering higher performance than the state of the art of Flash, one of their key features is lower power consumption, which makes them even more suitable for the IoT era. But one of the other main concerns regarding IoT is data security, which is yet to be evaluated for emerging NVM. Our previous work aimed at putting under test the integrity of HfO2 based resistive RAM (OxRAM cells). Bit-set occurrences were found after thermal laser attacks. This present work investigates the difference in behaviour when a selector is added to the resistive element, thanks to attack on different stacks. The results obtained give interesting tracks for the design of secure OxRAM-based ICs. It also studies the kinetic role of temperature through heating experiments.
The Ironies of Affirmative Action: Empirical Analyses of UC Students' Views on Fallacies and Problems of Affirmative Action

The 1990s may be said to have been tumultuous for affirmative action. They mark the culmination of profound disagreements over the moral and political status of affirmative action programs American citizens had an opportunity to decide whether affirmative action programs should be terminated from all federal programs. The Equal Opportunity Act introduced by Republican presidential candidate Robert Dole seeks to abolish three decades of affirmative action programs initiated by The intense debates on affirmative action have ranged over a number of social, political, and legal issues such as practical reasoning about effective policy making Surprisingly, one core controversy in the affirmative action debate is the disagreement over the social and legal definition of affirmative action-what affirmative action really involves and how affirmative action policies should be judged. Affirmative action policies have been subject to a variety of divergent interpretations. For instance, opponents of affim1ative action focus on quotas and preferences (Steele, 1990; Ward, 1995). By contrast, advocates of affirmative action concentrate on outreach, recruiting, and equal opportunities . [2] As a result, a variety of myths and fallacies have emerged on the definition and judgment of the policy of affirmative action, creating even greater controversies over the proprieties of race-or gender-conscious remedies to counteract inequities in modern The position taken in this paper seeks to expose certain inaccuracies or fallacies that permeate the opposition to affirmative action. Part I focuses on a variety of myths and misconceptions impacting affirmative action programs. This section places greater emphasis on race-conscious affirmative action programs than on gender considerations. Part II then provides an empirical analysis of University of California (UC) students' perceptions of affirmative action. Given that the UC system became the first major institution of higher education to abolish affirmative action programs based on race and gender considerations, UC students' views provide an important barometer of the relevance of gender-and color-blind policies. Finally, Part III discusses the current controversies over affirmative action and how misconceptions of affirmative action are entwined with attitudes towards the use of race-or gender-conscious remedies to rectify racial and gender discrimination. The main thrust of this paper, then, is intended to be both explanatory and prescriptive. It is explanatory insofar as it explains why many individuals misunderstand the intent and spirit of affirmative action, and prescriptive to the extent that its arguments and findings can form the basis for future affirn1ative action policies. By breaking down some of the …
Detecting and visualizing refactorings from software archives

We perform knowledge discovery in software archives in order to detect refactorings on the level of classes and methods. Our REFVIS prototype finds these refactorings in CVS repositories and relates them to transactions and configurations. Additionally, REFVIS relates movements of methods to the class inheritance hierarchy of the analyzed project. Furthermore, we present our visualization technique that illustrates these refactorings. REFVIS provides both a class hierarchy layout and a package layout and uses color coding to distinguish different kinds of refactorings. Details on each can be displayed on demand using mouse-over tooltips. Finally, we demonstrate by case studies on two open source projects how REFVIS facilitates understanding of refactorings applied to a software project.
Uncertainty Relations for Shift-Invariant Analog Signals

The past several years have witnessed a surge of research investigating various aspects of sparse representations and compressed sensing. Most of this work has focused on the finite-dimensional setting in which the goal is to decompose a finite-length vector into a given finite dictionary. Underlying many of these results is the conceptual notion of an uncertainty principle: a signal cannot be sparsely represented in two different bases. Here, we extend these ideas and results to the analog, infinite-dimensional setting by considering signals that lie in a finitely generated shift-invariant (SI) space. This class of signals is rich enough to include many interesting special cases such as multiband signals and splines. By adapting the notion of coherence defined for finite dictionaries to infinite SI representations, we develop an uncertainty principle similar in spirit to its finite counterpart. We demonstrate tightness of our bound by considering a bandlimited lowpass train that achieves the uncertainty principle. Building upon these results and similar work in the finite setting, we show how to find a sparse decomposition in an overcomplete dictionary by solving a convex optimization problem. The distinguishing feature of our approach is the fact that even though the problem is defined over an infinite domain with infinitely many variables and constraints, under certain conditions on the dictionary spectrum our algorithm can find the sparsest representation by solving a finite-dimensional problem.
Prospective Validation of Modified NEXUS Cervical Spine Injury Criteria in Low-risk Elderly Fall Patients

Introduction The National Emergency X-radiography Utilization Study (NEXUS) criteria are used extensively in emergency departments to rule out C-spine injuries (CSI) in the general population. Although the NEXUS validation set included 2,943 elderly patients, multiple case reports and the Canadian C-Spine Rules question the validity of applying NEXUS to geriatric populations. The objective of this study was to validate a modified NEXUS criteria in a low-risk elderly fall population with two changes: a modified definition for distracting injury and the definition of normal mentation. Methods This is a prospective, observational cohort study of geriatric fall patients who presented to a Level I trauma center and were not triaged to the trauma bay. Providers enrolled non-intoxicated patients at baseline mental status with no lateralizing neurologic deficits. They recorded midline neck tenderness, signs of trauma, and presence of other distracting injury. Results We enrolled 800 patients. One patient fall event was excluded due to duplicate enrollment, and four were lost to follow up, leaving 795 for analysis. Average age was 83.6 (range 65–101). The numbers in parenthesis after the negative predictive value represent confidence interval. There were 11 (1.4%) cervical spine injuries. One hundred seventeen patients had midline tenderness and seven of these had CSI; 366 patients had signs of trauma to the face/neck, and 10 of these patients had CSI. Using signs of trauma to the head/neck as the only distracting injury and baseline mental status as normal alertness, the modified NEXUS criteria was 100% sensitive (CI [67.9–100]) with a negative predictive value of 100 (98.7–100). Conclusion Our study suggests that a modified NEXUS criteria can be safely applied to low-risk elderly falls.