Miracle-dz/UniFAR-FTUs huggingface dataset:
Azd7009: a new antiarrhythmic drug with predominant effects on the atria effectively terminates and prevents reinduction of atrial fibrillation and flutter in the sterile pericarditis model.

INTRODUCTION We tested the hypothesis that AZD7009 terminates induced atrial fibrillation (AF) and flutter (AFL) and prevents their reinduction, and that effects on refractoriness, conduction, and excitability are predominantly on the atria. METHODS AND RESULTS Thirty-eight electrophysiologic studies were performed during AZD7009 infusion in 11 dogs with sterile pericarditis. The effects of AZD7009 on refractoriness, conduction, and capture threshold were studied and its antiarrhythmic efficacy tested. Simultaneous multisite biatrial mapping was performed in 7 dogs to assess arrhythmia termination. AZD7009 prolonged arrhythmia cycle length (CL) from 121 +/- 7.8 to 157 +/- 9.7 msec (P < 0.001) before terminating 23 of 23 AF/AFL episodes. Mapping demonstrated that AF/AFL CL prolonged and then terminated in area(s) of slow conduction in a reentrant circuit. Arrhythmia reinduction failed in 19 of 20 attempts. At 400-msec CL, atrial and ventricular refractoriness and QT interval increased 33%, 17% (P < 0.001 vs atrial refractoriness), and 9%, respectively. Atrial capture threshold increased in a CL-dependent manner: 1.8 +/- 0.3 to 2.2 +/- 0.3 mA (CL 400 msec); 2.1 +/- 0.3 to 2.8 +/- 0.5 mA (CL 300 msec), and 2.2 +/- 0.3 to 5.3 +/- 0.8 mA (CL 200 msec). Only minor nonsignificant changes occurred in the ventricles: 0.95 +/- 0.05 to 0.98 +/- 0.06 mA (CL 400 msec), and 1.14 +/- 0.12 to 1.16 +/- 0.13 mA (CL 333 msec). Atrial conduction time increased 8 +/- 1.4 msec (CL 400 msec), 8.3 +/- 1.5 msec (CL 300 msec), and 13.2 +/- 1.6 msec (CL 200 msec, all P < 0.001), but ventricular conduction time was unchanged. CONCLUSION AZD7009 is highly efficacious in terminating AF/AFL and preventing reinduction in this model. It exhibits marked effects on atrial electrophysiology but has only modest effects on the ventricle.
Adenine and guanine recognition of stop codon is mediated by different N domain conformations of translation termination factor eRF1

Positioning of release factor eRF1 toward adenines and the ribose-phosphate backbone of the UAAA stop signal in the ribosomal decoding site was studied using messenger RNA (mRNA) analogs containing stop signal UAA/UAAA and a photoactivatable cross-linker at definite locations. The human eRF1 peptides cross-linked to these analogs were identified. Cross-linkers on the adenines at the 2nd, 3rd or 4th position modified eRF1 near the conserved YxCxxxF loop (positions 125–131 in the N domain), but cross-linker at the 4th position mainly modified the tripeptide 26-AAR-28. This tripeptide cross-linked also with derivatized 3′-phosphate of UAA, while the same cross-linker at the 3′-phosphate of UAAA modified both the 26–28 and 67–73 fragments. A comparison of the results with those obtained earlier with mRNA analogs bearing a similar cross-linker at the guanines indicates that positioning of eRF1 toward adenines and guanines of stop signals in the 80S termination complex is different. Molecular modeling of eRF1 in the 80S termination complex showed that eRF1 fragments neighboring guanines and adenines of stop signals are compatible with different N domain conformations of eRF1. These conformations vary by positioning of stop signal purines toward the universally conserved dipeptide 31-GT-32, which neighbors guanines but is oriented more distantly from adenines.
Moderating Role of Gender between Job Characteristics and Job Satisfaction: An Empirical Study of Software Industry Using Structural Equation Modeling

This study examines the moderating role of gender between job characteristics and job satisfaction among Indian software employees which has received less attention in the Indian context. Additionally, it also examines difference in the job characteristics that affect male and female employee's job satisfaction. Structural Equation Modeling SEM and chi-square difference in multi group moderation analysis, used to test the hypothesized relationships. Chi-square difference test showed invariant moderation effect of gender on the relationship between job characteristics and job satisfaction. It has been also found that five job characteristics skill variety, task significance, task identity, autonomy and feedback have a significant positive impact on job satisfaction among male employees, whereas in case of female, only two job characteristics task significance and task identity were significant predictors of job satisfaction. Interestingly, task significance and task identity were common significant positive predictors of job satisfaction for both male and female software employees.
Inhibition of the Staphylococcus aureusNADPH-dependent Enoyl-Acyl Carrier Protein Reductase by Triclosan and Hexachlorophene*

Enoyl-acyl carrier protein reductase (FabI) plays a determinant role in completing cycles of elongation in type II fatty acid synthase systems and is an important target for antibacterial drugs. The FabI component of Staphylococcus aureus (saFabI) was identified, and its properties were compared with Escherichia coli FabI (ecFabI). ecFabI and saFabI had similar specific activities, and saFabI expression complemented the E. coli fabI(Ts) mutant, illustrating that the Gram-positive FabI was interchangeable with the Gram-negative FabI enzyme. However, ecFabI was specific for NADH, whereas saFabI exhibited specific and positive cooperative binding of NADPH. Triclosan and hexachlorophene inhibited both ecFabI and saFabI. The triclosan-resistant ecFabI(G93V) protein was also refractory to hexachlorophene inhibition, illustrating that both drugs bind at the FabI active site. Both the introduction of a plasmid expressing the safabI gene or a missense mutation in the chromosomal safabI gene led to triclosan resistance in S. aureus; however, these strains did not exhibit cross-resistance to hexachlorophene. The replacement of the ether linkage in triclosan by a carbon bridge in hexachlorophene prevented the formation of a stable FabI-NAD(P)+-drug ternary complex. Thus, the formation of this ternary complex is a key determinant of the antibacterial activity of FabI inhibitors.
Prostate-specific antigen in the early detection of prostate cancer

Throughout Canada, the United States and much of Europe, prostate-specific antigen (PSA) screening for prostate cancer has proliferated over the past 2 decades, leading to dramatic increases in detection rates of prostate cancer. Although it has unquestionably led to increased detection of cancer and a migration to lower-stage and -volume tumours, it is still unknown whether PSA screening significantly reduces mortality from prostate cancer. Often thought to be dichotomous (i.e., either normal or elevated), PSA measurements actually reflect cancer risk, with the risks of cancer and of aggressive cancer increasing with the level of PSA. The recently developed risk calculator from the Prostate Cancer Prevention Trial, which integrates family history of prostate cancer, digital rectal examination findings, PSA test result, age, ethnicity, and history of a prior prostate biopsy with a negative result, allows clinicians to assess a patient's individual risk of cancer. This risk should be examined in the context of a patient's life expectancy and comorbidity as well as his concern about the possibility of prostate cancer. The terms “normal” and “elevated” as descriptors of PSA results should be abandoned.
Beyond the long-term mean: exploring the potential of F0 distribution parameters in traditional forensic speaker recognition

Despite its many prima facie attractive properties for Forensic Speaker Recognition, F0 is regarded as having limited forensic value due to its large within-speaker variability. However, its forensic use to date has been limited mostly to its long-term mean and standard deviation. This paper examines the discriminatory potential, within a Likelihood Ratio-based approach, of additional parametric features from the distribution of long-term F0: its skew, kurtosis, modal F0 and modal density. Motivated by the observation that the overall long-term F0 distribution shows less within-speaker occasion-to-occasion difference, we report a forensic discrimination experiment with noncontemporaneous speech samples from 201 male Japanese speakers. Using a multivariate LR as discriminant distance with the six LTF0 distribution parameters, an EER of 10.7% is obtained from 201 target and 80400 non-target trials. We also investigate how the EER degrades as a function of amount of voiced speech.
A Phase I Dose Escalation Study of the Triple Angiokinase Inhibitor Nintedanib Combined with Low-Dose Cytarabine in Elderly Patients with Acute Myeloid Leukemia

Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg subcutaneous injection twice daily for 10 days) were administered in 28-day cycles. Dose-limiting toxicity (DLT) was defined as non-hematological severe adverse reaction CTC grade ≥ 4 with possible or definite relationship to nintedanib. Between April 2012 and October 2013, 13 patients (median age 73 [range: 62–86] years) were enrolled. One patient did not receive study medication and was replaced. Nine (69%) patients had relapsed or refractory disease and 6 (46%) patients had unfavorable cytogenetics. The most frequently reported treatment-related adverse events (AE) were gastrointestinal events. Twelve SAEs irrespective of relatedness were reported. Two SUSARs were observed, one fatal hypercalcemia and one fatal gastrointestinal infection. Two patients (17%) with relapsed AML achieved a complete remission (one CR, one CRi) and bone marrow blast reductions without fulfilling PR criteria were observed in 3 patients (25%). One-year overall survival was 33%. Nintedanib combined with LDAC shows an adequate safety profile and survival data are promising in a difficult-to-treat patient population. Continuation of this trial with a phase II recommended dose of 2 x 200 mg nintedanib in a randomized, placebo-controlled phase II study is planned. The trial is registered to EudraCT as 2011-001086-41. Trial Registration: ClinicalTrials.gov NCT01488344
The Effects of Walking and Cycling Computer Workstations on Keyboard and Mouse Performance

Objective: This study aimed to determine the effects of active workstation designs on speed and error during typing, mouse pointing, and combined type and mouse-use tasks. Background: Office ergonomics has focused on musculoskeletal disorder prevention; however, increasing computer-based work also increases health risks associated with inactivity. Workstations allowing computer users to walk or cycle while performing computer tasks have been shown to demand sufficient energy expenditure to result in significant health benefits. However the performance effects of being active while using a computer have not been documented. Method: Thirty office workers (16 female, 15 touch typists) performed standardized computer tasks in six workstation conditions: sitting, standing, walking at 1.6 km/h and 3.2 km/h, and cycling at 5 and 30 watts. Performance, perceived performance, and heart rate were measured. Results: Computer task performance was lower when walking and slightly lower when cycling, compared with chair sitting. Standing performance was not different from sitting performance. Mouse performance was more affected than typing performance. Performance decrements were equal for females and males and for touch typists and nontouch typists. Conclusion: Performance decrements maybe related to both biomechanical and cognitive processes. Active workstations may be less suitable for mouse-intensive work and susceptible users. Application: Although active workstations may result in some decrement in performance, their ability to increase daily energy expenditure may make them a feasible solution for workplace inactivity.
430 LIPOSOMAL DOXORUBICIN, CYCLOPHOSPHAMIDE, AND ETOPOSIDE AND ANTIRETROVIRAL THERAPY FOR PATIENTS WITH AIDS-RELATED LYMPHOMA: A PILOT STUDY.

Purpose To evaluate in a pilot study the safety and efficacy of liposomal doxorubicin in conjunction with cyclophosphamide and etoposide (LACE) and antiretroviral therapy (ART) in patients with AIDS-related lymphoma (ARL) and Hodgkin's disease (HD). The impact of HIV viral control on therapy and survival was also assessed. Patients and Methods Between 1994 and 2005, 50 patients were diagnosed with ARL (n = 40) and HD (n = 10) at VMMC, of whom 15 received liposomal doxorubicin (30 mg/m2 IV d1), cyclophosphamide (700 mg/m2 IV d1), and etoposide (60 mg/m2 IV d1 and 120 mg/m2 po d2-3) q 28 days. All patients received intrathecal chemoprophylaxis, ART, and G-CSF (d 3-12). Results The median patient CD4+ count was 181 cells/μL (range 20-853 cells/μL), and the median HIV VL was 34,011 copies/mL (range < 50-500,000 copies/mL). Eight patients (53%) had an International Prognostic Index score of 3 or 4. Six patients (40%) were ART naïve, 7 patients were viremic despite ART, and 2 had an undetectable HIV VL. Eleven patients (73%) achieved a complete response (CR), and the median overall survival was 62.6 months. At a median follow-up of 29 months, recurrence-free survival is 47%. Three patients died from relapsed/refractory ARL and 2 patients achieved CR with salvage therapy. One CR patient died from complications of pneumonia and another CR patient died from uncertain causes 5 years after treatment. Grade 3 or 4 neutropenia occurred in 33 of 78 (42%) chemotherapy cycles. Hospitalization was required after 4% of treatment cycles due to neutropenic fever. Conclusion LACE is an effective and tolerable treatment for ARL. HIV viral control could be maintained in the majority of patients during and after completion of LACE.
Rationale and design of the GRACE (Global Registry of Acute Coronary Events) Project: a multinational registry of patients hospitalized with acute coronary syndromes.

BACKGROUND Acute coronary syndromes (ACS), including the spectrum of conditions from unstable angina to ST segment elevation myocardial infarction, represent a major cause of morbidity and mortality throughout the world. GRACE (the Global Registry of Acute Coronary Events) is a large, prospective, multinational observational study of patients hospitalized with ACS. The aim of GRACE is to improve the quality of care for patients with ACS by describing differences in, and relationships between, patient characteristics, treatment practices, and in-hospital and postdischarge outcomes at hospitals around the world. A goal of this study is to study approximately 10,000 patients with ACS on an annual basis. METHODS A total of 18 cluster sites in 14 countries in North America, South America, Europe, Australia, and New Zealand are currently collaborating in GRACE. Clusters were chosen on the basis of local demographic characteristics and hospital facilities to ensure a representative sample of patients with ACS from each country. Patients are identified by use of either active or passive surveillance approaches. A standardized core case report form is completed for all patients. Information on patient demographics, medical history, acute symptoms, clinical characteristics, electrocardiographic findings, treatment approaches, and in-hospital outcomes is collected. Patients are followed up at 6 months after hospital discharge to identify recurrent coronary events, use of various medications, and mortality. CONCLUSIONS The information collected from the GRACE project will provide important and extensive insights into patient demographic and clinical characteristics, current practice patterns, and outcomes for patients with ACS from a number of countries throughout the world. Given the pressures of practicing evidence-based medicine, the results of GRACE should provide a multinational perspective into these important outcomes and identify practice variations that will allow new opportunities to improve patient care.
Glypican-3-Expressing Hepatocellular Carcinoma in a Non-Cirrhotic Patient with Nonalcoholic Steatohepatitis: Case Report and Literature Review

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Nonalcoholic steatohepatitis (NASH) is now considered as the major cause of cryptogenic cirrhosis, which can progress to HCC. Glypican-3 is a member of the Heparan Sulfate Proteoglycan (HSP) family that plays a role in cell growth, differentiation, and migration. Glypican-3 is significantly up-regulated in a majority of HCCs compared to normal and benign liver samples. Glypican-3 protein is detectable in around 40-53% of HCC patients whereas it is not detectable in the serum of healthy individuals. There are several reports of HCC arising in the setting of non-cirrhotic NASH. This report describes a case of HCC that expressed Glypican-3 and arose in a 47-year-old female with noncirrhotic NASH.
Physikit: Data Engagement Through Physical Ambient Visualizations in the Home

Internet of things (IoT) devices and sensor kits have the potential to democratize the access, use, and appropriation of data. Despite the increased availability of low cost sensors, most of the produced data is "black box" in nature: users often do not know how to access or interpret data. We propose a "human-data design" approach in which end-users are given tools to create, share, and use data through tangible and physical visualizations. This paper introduces Physikit, a system designed to allow users to explore and engage with environmental data through physical ambient visualizations. We report on the design and implementation of Physikit, and present a two-week field study which showed that participants got an increased sense of the meaning of data, embellished and appropriated the basic visualizations to make them blend into their homes, and used the visualizations as a probe for community engagement and social behavior.
Online Algorithms for Covering and Packing Problems with Convex Objectives

We present online algorithms for covering and packing problems with (non-linear) convex objectives. The convex covering problem is defined as: min<sub>xϵ</sub>R<sub>+</sub><sup>n</sup>f(x) s.t. Ax ≥ 1, where f:R<sub>+</sub><sup>n</sup> → R<sub>+</sub> is a monotone convex function, and A is an m×n matrix with non-negative entries. In the online version, a new row of the constraint matrix, representing a new covering constraint, is revealed in each step and the algorithm is required to maintain a feasible and monotonically non-decreasing assignment x over time. We also consider a convex packing problem defined as: max<sub>yϵR+</sub><sup>m</sup> Σ<sub>j=1</sub><sup>m</sup> yj - g(A<sup>T</sup> y), where g:R<sub>+</sub><sup>n</sup>→R<sub>+</sub> is a monotone convex function. In the online version, each variable yj arrives online and the algorithm must decide the value of yj on its arrival. This represents the Fenchel dual of the convex covering program, when g is the convex conjugate of f. We use a primal-dual approach to give online algorithms for these generic problems, and use them to simplify, unify, and improve upon previous results for several applications.
The Impact of the Introduction and Use of an Informational Website on Offline Customer Buying Behavior

Do customers increase or decrease their spending in response to the introduction of an informational website? To answer this question, this study considers the effects of the introduction and use of an informational website by a large national retailer on offline customer buying behavior. More specifically, we study a website's effects on the number of shopping trips and the amount spent per category per shopping trip. The model is calibrated through the estimation of a Poisson model (shopping trips) and a type-II tobit model (the amount spent per category per shopping trip), with effect parameters that vary across customers. For the focal retailer, an informational website creates more bad than good news; most website visitors engage in fewer shopping trips and spend less in all product categories. The authors also compare the characteristics of shoppers who exhibit negative website effects with those few shoppers who show positive effects and thus derive key implications for research and practice.
Universal viscosity behavior of polycondensation polymer/silica nanocomposites

Viscosity control is very important in polymer processing. Recent studies suggest that melt viscosity can be reduced by the addition of nanoparticles without compromising the mechanical properties. In this chapter, the rheological behavior of poly(carbonate) (PC) and poly(styrene) (PS) and nanosilica composites prepared via melt compounding is investigated by means of oscillatory shear rheology, Fourier transform infrared spectroscopy (FTIR), X-ray Photoelectron Spectroscopy (XPS), and differential scanning calorimetry (DSC). The melt viscosity behavior of the nanocomposites was found to depend on the interaction between the polymer matrix and the nanoparticle surface. The PS nanocomposite exhibited a viscosity increase for all nanosilica concentrations, while PC nanocomposites exhibit a decrease in viscosity of up to 25% at concentrations below 0.7 vol% of nanosilica, followed by a increase thereafter. FTIR, XPS and DSC revealed that the decrease in viscosity could be attributed to the grafted PC chains on the nanosilica surface that caused disentanglement in the surroundings of the nanoparticle. The thickness of the grafted layer was found to be approximately equal to the tube diameter. Furthermore, it is shown that the grafting has a profound effect on the motions of the PC on all timescales. At shorter timescales the nanoparticles were found to impose additional constraints on the tube thereby constraining the motion of the PC chain, while at longer timescales the grafts reduced the entanglement density at the nanosilica-PC interface resulting in the formation of a low viscous layer which speeds up the relaxation of PC. The influence zone of these grafts was calculated to be of the order of Rg using the Wang-Hill model. Finally, the viscosity behavior in the PC nanocomposites was found to be independent of the molar mass and Rg of PC within the tested range. These results highlight that by choosing the right polymer-particle system and tuning the interaction between them, unique and enhanced bulk properties can be achieved.
Nucleotide sequencing and characterization of Pseudomonas putida catR: a positive regulator of the catBC operon is a member of the LysR family

Pseudomonas putida utilizes the catBC operon for growth on benzoate as a sole carbon source. This operon is positively regulated by the CatR protein, which is encoded from a gene divergently oriented from the catBC operon. The catR gene encodes a 32.2-kilodalton polypeptide that binds to the catBC promoter region in the presence or absence of the inducer cis-cis-muconate, as shown by gel retardation studies. However, the inducer is required for transcriptional activation of the catBC operon. The catR promoter has been localized to a 385-base-pair fragment by using the broad-host-range promoter-probe vector pKT240. This fragment also contains the catBC promoter whose -35 site is separated by only 36 nucleotides from the predicted CatR translational start. Dot blot analysis suggests that CatR binding to this dual promoter-control region, in addition to inducing the catBC operon, may also regulate its own expression. Data from a computer homology search using the predicted amino acid sequence of CatR, deduced from the DNA sequence, showed CatR to be a member of a large class of procaryotic regulatory proteins designated the LysR family. Striking homology was seen between CatR and a putative regulatory protein, TfdS.