Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure-Function Relationships Underlying the Replication Fidelity of Viral RNA-Dependent RNA Polymerases

ABSTRACT Viral RNA-dependent RNA polymerases are considered to be low-fidelity enzymes, providing high mutation rates that allow for the rapid adaptation of RNA viruses to different host cell environments. Fidelity is tuned to provide the proper balance of virus replication rates, pathogenesis, and tissue tropism needed for virus growth. Using our structures of picornaviral polymerase-RNA elongation complexes, we have previously engineered more than a dozen coxsackievirus B3 polymerase mutations that significantly altered virus replication rates and in vivo fidelity and also provided a set of secondary adaptation mutations after tissue culture passage. Here we report a biochemical analysis of these mutations based on rapid stopped-flow kinetics to determine elongation rates and nucleotide discrimination factors. The data show a spatial separation of fidelity and replication rate effects within the polymerase structure. Mutations in the palm domain have the greatest effects on in vitro nucleotide discrimination, and these effects are strongly correlated with elongation rates and in vivo mutation frequencies, with faster polymerases having lower fidelity. Mutations located at the top of the finger domain, on the other hand, primarily affect elongation rates and have relatively minor effects on fidelity. Similar modulation effects are seen in poliovirus polymerase, an inherently lower-fidelity enzyme where analogous mutations increase nucleotide discrimination. These findings further our understanding of viral RNA-dependent RNA polymerase structure-function relationships and suggest that positive-strand RNA viruses retain a unique palm domain-based active-site closure mechanism to fine-tune replication fidelity. IMPORTANCE Positive-strand RNA viruses represent a major class of human and animal pathogens with significant health and economic impacts. These viruses replicate by using a virally encoded RNA-dependent RNA polymerase enzyme that has low fidelity, generating many mutations that allow the rapid adaptation of these viruses to different tissue types and host cells. In this work, we use a structure-based approach to engineer mutations in viral polymerases and study their effects on in vitro nucleotide discrimination as well as virus growth and genome replication fidelity. These results show that mutation rates can be drastically increased or decreased as a result of single mutations at several key residues in the polymerase palm domain, and this can significantly attenuate virus growth in vivo. These findings provide a pathway for developing live attenuated virus vaccines based on engineering the polymerase to reduce virus fitness.
Surgical treatment of the Charcot foot

With the increased number of diabetics worldwide and the increased incidence of morbid obesity in more prosperous cultures, there has become an increased awareness of Charcot arthropathy of the foot and ankle. Outcome studies would suggest that patients with deformity associated with Charcot Foot arthropathy have impaired health related quality of life. This awareness has led reconstructive‐minded foot and ankle surgeons to develop surgical strategies to treat these acquired deformities. This article outlines the current clinical approach to this disabling medical condition. Copyright © 2016 John Wiley & Sons, Ltd.
Validated Assessment Scales for Décolleté Wrinkling and Pigmentation

BACKGROUND Décolleté aging includes skin dyspigmentation, laxity, and visible wrinkling. The development of globally accepted scales for the assessment of décolleté aging is essential for aesthetic research and patient evaluation. OBJECTIVE To develop a set of grading scales for the objective assessment of décolleté aging criteria and establish the reliability and validity of these scales. MATERIALS AND METHODS To describe age-related changes to the décolleté, 3 photonumeric grading scales were created and validated: décolleté wrinkles—at rest, décolleté wrinkles—dynamic, and décolleté pigmentation—at rest. Thirteen aesthetic experts rated photographs of the décolleté of 50 women at rest and at dynamic “hand-to-elbow” positions in 2 validation sessions. Responses were analyzed to assess interrater and intrarater reliability. RESULTS Interrater and intrarater reliability were both “almost perfect” (≥0.81, intraclass correlation coefficient and weighted kappa) for décolleté wrinkles—dynamic, summary score for décolleté, and estimated age. Reliability was “substantial” (0.61–0.80) for all other décolleté assessments. There was high correlation between all décolleté scales, estimated age, and estimated aesthetic treatment effort. CONCLUSION Consistent outcomes between raters and by individual raters at different time points confirm the reliability of the décolleté grading scales, indicating that they will be a valuable tool for use in clinical research and practice.
An Attack Vector for Deception Through Persuasion Used by Hackers and Crakers

We always uses the Anti-virus or Anti- Spyware software to secure our data but still most of our computers are infected by the Malware because we thought computer security as just technical field and anti-virus or firewall only can prevent us. Despite all the technological advancement in security, there is still one attack vector that leaves our network and computer unsecured. Psychology; Hackers and crackers are adept at psychologically for manipulating people into giving them access or the information necessary to get access using a variety of Techniques. People have a natural instinct to trust and help other people. This paper discusses the inner working of social engineering. One case study of Spyware is provided, in this case study. We got 100% success using social engineering techniques. As well as few other case studies of social engineering is also given and this will give vital information on combating social engineering. Defending techniques against social engineering is also provided which will prove significant in preventing such attacks.
TACO: Visualizing Changes in Tables Over Time

Multivariate, tabular data is one of the most common data structures used in many different domains. Over time, tables can undergo changes in both structure and content, which results in multiple versions of the same table. A challenging task when working with such derived tables is to understand what exactly has changed between versions in terms of additions/deletions, reorder, merge/split, and content changes. For textual data, a variety of commonplace “diff” tools exist that support the task of investigating changes between revisions of a text. Although there are some comparison tools which assist users in inspecting differences between multiple table instances, the resulting visualizations are often difficult to interpret or do not scale to large tables with thousands of rows and columns. To address these challenges, we developed TACO, an interactive comparison tool that visualizes the differences between multiple tables at various levels of detail. With TACO we show (1) the aggregated differences between multiple table versions over time, (2) the aggregated changes between two selected table versions, and (3) detailed changes between the selected tables. To demonstrate the effectiveness of our approach, we show its application by means of two usage scenarios.
Changes in neuropsychological performance of AIDS‐related complex patients who progress to AIDS

ObjectiveTo investigate the changes in neuropsychological performance associated with progression from AIDS-related complex (ARC) to AIDS. DesignA repeated measures design was used to compare three groups: ARC patients who progressed to AIDS (n = 15), those who did not (n = 19) and seronegative controls (n = 16). MethodsThe three groups were compared on tests of memory, information processing, motor performance, attention and conceptual flexibility. Clinical and immunological characteristics were recorded. Rates of neuropsychological impairment among the three groups were calculated and compared. ResultsThe only significant difference between the groups at baseline was for one measure of motor performance. Repeated measures analysis indicated that there was a differential rate of change for the three subject groups for tasks of motor performance and attention. ARC patients who progressed to AIDS did not differ significantly from the non-progressors, although both groups showed significant deterioration over time compared with seronegative controls. Although there was a tendency for the progressors to have a higher rate of impairment, there were no consistent significant differences between visits. ConclusionThere were no significant changes in performance exclusively associated with progression to AIDS.
CB1 knockout mice display impaired functionality of 5‐HT1A and 5‐HT2A/C receptors

Interaction between brain endocannabinoid (EC) and serotonin (5‐HT) systems was investigated by examining 5‐HT‐dependent behavioral and biochemical responses in CB1 receptor knockout mice. CB1 knockout animals exhibited a significant reduction in the induction of head twitches and paw tremor by the 5‐HT2A/C receptor selective agonist (±) DOI, as well as a reduced hypothermic response following administration of the 5‐HT1A receptor agonist (±)‐8‐OH‐DPAT. Additionally, exposure to the tail suspension test induced enhanced despair responses in CB1 knockout mice. However, the tricyclic antidepressant imipramine and the 5‐HT selective reuptake inhibitor fluoxetine induced similar decreases in the time of immobility in the tail suspension test in CB1 receptor knockout and wild‐type mice. No differences were found between both genotypes with regard to 5‐HT2A receptor and 5‐HT1A receptors levels, measured by autoradiography in different brain areas. However, a significant decrease in the ability of both, the 5‐HT1A receptor agonist (±)‐8‐OH‐DPAT and the 5‐HT2A/C receptor agonist (−)DOI, to stimulate [35S]GTPγS binding was detected in the hippocampal CA1 area and fronto‐parietal cortex of CB1 receptor knockout mice, respectively. This study provides evidence that CB1 receptors are involved in the regulation of serotonergic responses mediated by 5‐HT2A/C and 5‐HT1A receptors, and suggests that a reduced coupling of 5‐HT1A and 5‐HT2A receptors to G proteins might be involved in these effects.
Tensions and synergies in the Central Valley of Tarija, Bolivia: commercial viticulture and agrobiodiversity in smallholder farming systems

ABSTRACT New policy directions supporting small-scale, ecologically diverse agriculture often remain un-reconciled with decades of modernist agricultural development. We examine the case of campesino grape producers in the Central Valley of Tarija, Bolivia, and how and why they combine commercial grape production with species-level agrobiodiversity. High production costs and ecological and economic risks of viticulture, alongside other species’ sociocultural and economic values, are factors informing campesino production strategies. The importance of agrobiodiversity for campesino viticulturalists, however, is underrecognized by rural development authorities and we discuss opportunities to narrow the persisting gaps between rural development theory and practice in the Central Valley.
The Americans With Disabilities Act and Test Anxiety: When Accommodations Are Appropriate

The Americans with Disabilities Act (ADA) requires institutions of higher learning, including health professional training programs, to abide by the regulations set forth governing the provision of accommodations for students with disabilities. Accommodations are provided when a disability substantially limits one or more major life activities, which include reading, learning, communicating, and working. One request that professional programs may receive comes from the student seeking special accommodations for test-taking anxiety and the challengeof determiningwhether the student has genuine impairment or whether the anxiety is simply a normal physiologic response. This article provides some guidelines to consider in determining the obligations of the program to the student who is requesting this accommodation.
Socioeconomic differences in risk of myocardial infarction 1971-1994 in Sweden: time trends, relative risks and population attributable risks.

BACKGROUND The general trend in incidence of myocardial infarction (MI) in the Stockholm area changed from increasing to decreasing around 1980. The objective of this study is to examine time trends in incidence in major socioeconomic strata, relative risk between socioeconomic groups and population risk attributable to socioeconomic differences during this period. METHODS All cases of MI from 1971 to 1986 were identified from hospital discharge and cause-of-death registers. Person-years for each year of follow-up were calculated from the population register in the Stockholm region 1971-1986. Census registers were used for information on socioeconomic status. Register information was individually linked through the Swedish personal identification number. Supplementary information for 1992-1994 was taken from the case-control study SHEEP (Stockholm Heart Epidemiology Program). RESULTS The decline in MI risk among male high- and middle-level employees started in 1976 and in male manual workers in 1981. For women incidence increased from 1971 to 1986 among manual workers and decreased among high- and middle-level employees. The increase over time of the relative risk from low socioeconomic position continued into the 1990s. Despite the reduction of the category of manual workers, the population attributable risk from socioeconomic differences also increased over time. The process of social change influencing the size of the socioeconomic groups contributes to the change in time trends of MI morbidity. CONCLUSIONS The increase over time of relative and population attributable risks of MI from low socioeconomic status add to the public health importance of social inequity.
Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons.

BACKGROUND Lower muscle mass has been correlated with poor physical function; however, no studies have examined this relationship prospectively. This study aims to investigate whether low muscle mass, low muscle strength, and greater fat infiltration into the muscle predict incident mobility limitation. METHODS Our study cohort included 3075 well-functioning black and white men and women aged 70-79 years participating in the Health, Aging, and Body Composition study. Participants were followed for 2.5 years. Muscle cross-sectional area and muscle tissue attenuation (a measure of fat infiltration) were measured by computed tomography at the mid-thigh, and knee extensor strength by using a KinCom dynamometer. Incident mobility limitation was defined as two consecutive self-reports of any difficulty walking one-quarter mile or climbing 10 steps. RESULTS Mobility limitations were developed by 22.3% of the men and by 31.8% of the women. Cox's proportional hazards models, adjusting for demographic, lifestyle, and health factors, showed a hazard ratio of 1.90 [95% confidence interval (CI), 1.27-2.84] in men and 1.68 (95% CI, 1.23-2.31) in women for the lowest compared to the highest quartile of muscle area (p <.01 for trend). Results for muscle strength were 2.02 (95% CI, 1.39-2.94) and 1.91 (95% CI, 1.41-2.58), p <. 001 trend, and for muscle attenuation were 1.91 (95% CI, 1.31-2.83) and 1.68 (95% CI, 1.20-2.35), p <. 01 for trend. When included in one model, only muscle attenuation and muscle strength independently predicted mobility limitation (p < .05). Among men and women, associations were similar for blacks and whites. CONCLUSION Lower muscle mass (smaller cross-sectional thigh muscle area), greater fat infiltration into the muscle, and lower knee extensor muscle strength are associated with increased risk of mobility loss in older men and women. The association between low muscle mass and functional decline seems to be a function of underlying muscle strength.
Rotavirus Spike Protein VP4 Binds to and Remodels Actin Bundles of the Epithelial Brush Border into Actin Bodies

ABSTRACT We demonstrate here that VP4, a rotaviral protein, is able to specifically bind to bundled actin microfilaments that are subsequently profoundly remodeled into actin bodies. These cytoplasmic actin bodies do not localize within identified intracellular compartments. VP4-induced actin remodeling is similar to cytochalasin D effects with kinetics compatible with that of rotavirus infection. Actin bundles' remodeling occurs both in infected and in VP4-transfected cells and in various cell lines, indicating that this is a general property of the viral protein itself. Interestingly, in intestinal epithelial cells, which represent the natural target of rotavirus, VP4 is addressed to the apical membrane where it binds specifically to brush border actin bundles and elicits its remodeling, whereas cytochalasin D impaired all the filamentous actin. These observations indicate that these original properties of VP4 likely explain the previously described brush border alterations that follow rotavirus infection of enterocytes and may also participate to the mechanism of rotavirus final assembly.
Immunocytochemical localization of the GABA transporter in rat brain

Polyclonal antibodies were raised against the GABA transporter (GABA- Tp) purified from rat brain tissue (Radian et al., 1986) and used for immunocytochemical localization of the antigen in several rat brain areas, including the cerebellum, hippocampus, substantia nigra, and cerebral cortex. Light microscopic studies with the peroxidase- antiperoxidase and biotin-avidin-peroxidase techniques suggested that GABA-Tp is localized in the same types of axons and terminals that contain endogenous GABA, as judged by comparison with parallel sections incubated with antibodies against glutaraldehyde-conjugated GABA. However, as expected from biochemical results, different neurons differed in their relative contents of GABA-Tp and GABA; thus, GABA-Tp was relatively low in striatonigral and Purkinje axon terminals and relatively high in nerve plexus around the bases of cerebellar Purkinje cells and hippocampal pyramidal and granule cells. The GABA-Tp antiserum did not produce detectable labeling of nerve cell bodies. Electron microscopic studies supported the light microscopic observations and provided direct evidence of cellular co-localization of GABA-Tp and GABA (as visualized by the peroxidase-antiperoxidase technique and postembedding immunogold labeling, respectively). The ultrastructural studies indicated the presence of GABA-Tp also in glial processes but not in glial cell bodies. The relative intensity of the neuronal and glial staining varied among regions: glial staining predominated over neuronal staining in the substantia nigra, whereas the converse was true in the cerebellum and hippocampus. The present immunocytochemical data demonstrate directly what has previously been inferred from biochemical and autoradiographic evidence: that the mechanisms for high-affinity GABA uptake is selectively and differentially localized in GABAergic neurons and in glial cells.
REGRESSION, THEIL'S AND MLP FORECASTING MODELS OF STOCK INDEX

Financial Forecasting or specifically Stock Market prediction is one of the hottest fields of research lately due to its commercial applications owing to the high stakes and the kinds of attractive benefits that it has to offer. Financial time-series is one of the ‘noisiest’ and ‘non-stationary’ signals present and hence very difficult to forecast. In this paper we have made an attempt to forecast the daily prices of stock index using a Regression, Theil’s and MLP models and the predictive ability of these models are compared using standard error measures.
[Incremental doses of diltiazem in patients with coronary artery disease in end-stage renal failure maintained on hemodialysis: which is the optimal dose?].

End-stage renal disease patients on maintenance hemodialysis suffering from coronary artery disease probably receive too low doses of calcium-antagonists, because the attempt to avoid adverse effects prevails the well-documented antianginal activity of the drug. The aim of our study was to assess the safety and efficacy of incremental doses of diltiazem in treating angina pectoris in hemodialyzed patients with coronary artery disease, to identify the optimal dose. Ninety-four chronic hemodialyzed patients (59 males and 35 females; mean age 55.2 +/- 3.3 years; on periodic dialysis for 80.3 +/- 25.6 months) with coronary artery disease and more than 5 min of transient myocardial ischemia during 48 hours of Holter monitoring were included in the study. A double-blind, randomized, placebo-controlled trial design was used. Incremental doses of diltiazem (from 120 to 240 mg/day) were administered in 4 months. At doses of 120 and 180 mg/day it was observed a statistically significant reduction in the number and duration of total and symptomatic ischemic episodes in 48 hours, compared with baseline (p < 0.001). Instead, the number and the duration of silent ischemic episodes did not significantly change (NS). The efficacy on silent myocardial ischemia was obtained only with the dosage of 240 mg/day (p < 0.001). If this dosage was obtained with a sustained-release formulation (120 mg twice a day), the efficacy was similar to the administration of 4 tablets/day of 60 mg, but the tolerability was better, especially during dialysis. The circadian variations of transient ischemic episodes showed two peaks in the 24 hours, one from 6.00 to 9.00 a.m. and another from 4.00 to 8.00 p.m. , just during the dialysis. Both peaks were reduced only with 240 mg/day. In conclusion, this study demonstrates that sustained-release diltiazem (120 mg twice a day) is greatly useful in patients with coronary artery disease on maintenance dialysis because it reduces the frequency of silent ischemic episodes, has a good tolerability, and modifies the circadian pattern of ischemic episodes, reducing both peaks during the day.
Feature Point Detection in Image Morphing Based Steganography

In today's society, information hiding is becoming a key mechanism to protecting one's secrets. In our study, we have proposed several new information hiding methods based on image morphing. To synthesize a large number of virtual but natural images through morphing to cover different kinds of secrets, it is necessary to propose some efficient and effective method for automatic feature point detection. For this purpose, we proposed a method based on iterative evolutionary algorithm (IEA) earlier. This method, however, is not efficient because it is too time consuming. In this paper, we propose a neural network (NN) based method for feature point detection. The basic idea is to detect a neighborhood of a specified feature point, and use the center of the neighborhood as the estimated position of the feature point. The performance of the proposed method is verified through experiments.