Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-Wide Mutational Signature of the Chemotherapeutic Agent Mitomycin C in Caenorhabditis elegans

Cancer therapy largely depends on chemotherapeutic agents that generate DNA lesions. However, our understanding of the nature of the resulting lesions as well as the mutational profiles of these chemotherapeutic agents is limited. Among these lesions, DNA interstrand crosslinks are among the more toxic types of DNA damage. Here, we have characterized the mutational spectrum of the commonly used DNA interstrand crosslinking agent mitomycin C (MMC). Using a combination of genetic mapping, whole genome sequencing, and genomic analysis, we have identified and confirmed several genomic lesions linked to MMC-induced DNA damage in Caenorhabditis elegans. Our data indicate that MMC predominantly causes deletions, with a 5′-CpG-3′ sequence context prevalent in the deleted regions of DNA. Furthermore, we identified microhomology flanking the deletion junctions, indicative of DNA repair via nonhomologous end joining. Based on these results, we propose a general repair mechanism that is likely to be involved in the biological response to this highly toxic agent. In conclusion, the systematic study we have described provides insight into potential sequence specificity of MMC with DNA.
Pharmacokinetics, efficacy and safety profiles of etanercept monotherapy in Japanese patients with rheumatoid arthritis: review of seven clinical trials

Abstract Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The aim of this review was to summarize the clinical program for ETN monotherapy in Japanese patients with RA, which has included a pharmacokinetic study, clinical trials for registration, long-term studies, and once-weekly dosing studies. Pharmacokinetic results showed that serum concentrations of ETN were linear with dose levels and were similar to other international studies. Across interventional studies, 652 Japanese patients with active RA were treated with ETN. In the registration studies, ETN treatment led to consistent improvement in American College of Rheumatology 20/50/70 scores, European League Against Rheumatism Good Response, Disease Activity Score 28 erythrocyte sedimentation rate remission, and Health Assessment Questionnaire disability index. In the long-term studies, efficacy was maintained for up to 180 weeks. Similar results were seen in the once-weekly studies. Across the studies, more than 870 patient-years of exposure to ETN were recorded. Discontinuations owing to lack of efficacy or adverse events were modest and no new safety signals were recorded. These studies demonstrated that ETN monotherapy is efficacious and well-tolerated in Japanese patients with RA.
Comparative Study of VLSI Solutions to Independent Component Analysis

The advent of independent component analysis (ICA) has brought a paradigm shift to signal and image processing. ICA that extracts independent source signals by searching for a linear or nonlinear transformation and minimizing the statistical dependence between components has the promise of effective unsupervised signal separation capability. Due to the computation complexity of ICA and commonly high-volume data sets used in signal and image processing, the ICA process, however, is very time-consuming. Very large scale integration (VLSI) solutions with optimal parallelism provide potentially faster and even real-time implementations for ICA algorithms. In this paper, the authors study these solutions and discuss their limits. Critical challenges are identified, and issues associated with the VLSI implementation of ICA algorithms are designed. Design recommendations that have potentials in performing complicated ICA algorithms on large throughput are provided
Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid

Abstract Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN) alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA) in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (p<0.05) reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) content. Malondialdehyde, hydrogen peroxide (H2O2) and nitric oxide (NO) contents were also significantly (p<0.05) elevated following DZN exposure. DZN further caused a significant (p<0.05) decrease of heart rate and QT interval prolongation. Hematologic analysis revealed significant reduction (p<0.05) in packed cell volume (PCV), hemoglobin concentration (Hb), red blood cell (RBC) count, and total white blood cell count of rats administered only DZN. Observations in this study suggest a modulatory role of gallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened.
Globalization for Sale

We study the role of firms in the political economy of trade agreements. Using detailed information from lobbying reports filed under the Lobbying Disclosure Act, we find that virtually all firms that lobby on free trade agreements (FTAs) support their ratification. Moreover, relative to non-lobbying firms, lobbying firms are larger, and more likely to be engaged in international trade and to operate in comparative advantage sectors. To rationalize these findings, we develop a model in which heterogeneous firms decide whether to lobby and how much to spend in favor or against a proposed FTA. We show that the distributional effects are asymmetric: the winners from the FTA have higher stakes in the agreement than the losers, which explains why only pro-FTA firms select into lobbying. The model also delivers predictions on the intensive margin of lobbying. In line with these predictions, we find that firms spend more supporting agreements that generate larger potential gains - in terms of the extent of the reduction of tariffs on their final goods and intermediate inputs, the depth of the agreement, and the export and sourcing potential of the FTA partners - and when politicians are less likely to be in favor of ratification.
Salmonella virulence factor SipB induces activation and release of IL‐18 in human dendritic cells

Interleukin‐18 (IL‐18) plays an important role in innate and acquired immunity, in particular against intracellular pathogens. However, little is known about the microbial factors that trigger IL‐18 secretion by dendritic cells (DCs). To determine the influence of bacterial virulence factors on the activation and release of IL‐18, we infected human monocyte‐derived DCs with virulence mutants of the facultative intracellular pathogen Salmonella typhimurium. Our results show that infection by S. typhimurium causes caspase‐1‐dependent activation of IL‐18 and triggers the release of IL‐18 in human DCs. The secretion of IL‐18 by the DCs was closely correlated with the ability of the S. typhimurium strains to induce apoptosis. We demonstrate that activation and release of IL‐18 are blocked by mutations in the Salmonella sipB gene, which encodes a virulence factor that activates caspase‐1 to induce apoptosis. These findings indicate that the activation and release of IL‐18 induced by bacterial virulence factors may represent one component of innate immunity against the intracellular bacteria.
Informal learning with PDAs and smartphones

There has been increasing interest in informal learning in recent years alongside interest in how such learning can be supported by technology. However, relatively little is known about the extent to which adults make use of their own mobile devices to support informal learning. In this study, a survey was used to investigate whether, and to what extent, experienced users of mobile devices use their mobile devices to support intentional informal learning. If so, do they make use of mobile device connectivity to support opportunistic informal learning and does such connectivity support or encourage collaborative informal learning? Experienced mobile device users were recruited from web forums and business, and asked whether they used their devices to support informal learning. A pattern of learning uses emerged, some of which deployed the mobile device capabilities relatively unchanged, others triggered adaptations to typical learning activities to provide a better fit to the needs of the learner. These informal learning activities provided the basis for the design of a flexible mobile learning framework that can be extended to support developments in mobile technology, and increasing use of Web 2.0 technologies by informal learners.
Integrating Interpretive and Quantitative Methods in Socialization Research.

Those who study children's socialization are currently debating the relative merits of interpretive and quantitative approaches in research. In practice, an integrated research program in which both approaches are used in generating hypotheses, categories, measures, quantitative data, and interpretations can profit from the strengths of both approaches while compensating for their weaknesses. Three studies of the Yupno, Fiji, and Maya show how the interpretive approach contributes an understanding of the meaning of behavior in context whereas the quantitative approach contributes a precision of measurement that makes generalizations and comparisons possible
An Evaluation of Bias in Three Measures of Teacher Quality: Value-Added, Classroom Observations, and Student Surveys

There are three primary measures of teaching performance: student test-based measures (i.e., value added), classroom observations, and student surveys. Although all three types of measures could be biased by unmeasured traits of the students in teachers’ classrooms, prior research has largely focused on the validity of value-added measures. We conduct an experiment involving 66 mathematics teachers in four school districts and test the validity of all three types of measures. Specifically, we test whether a teacher’s performance on each measure under naturally occurring (i.e., non-experimental) settings predicts performance following random assignment of that teacher to a class of students. Combining our results with those from two previous experiments, we provide further evidence that value-added measures are unbiased predictors of teacher performance. In addition, we provide the first evidence that classroom observation scores are unbiased predictors of teacher performance on a rubric measuring the quality of mathematics instruction. Unfortunately, we lack the statistical power to reach any similar conclusions regarding the predictive validity of a teacher’s student survey responses.
Cytology and human papillomavirus screening test results associated with 2827 histopathologic diagnoses of cervical intraepithelial neoplasia 2/3.

CONTEXT Cervical screening in the United States increasingly involves newer US Food and Drug Administration-approved cytologic methods and adjunctive high-risk human papillomavirus (hrHPV) DNA testing. OBJECTIVE To document cervical screening test performance preceding histopathologic cervical intraepithelial neoplasia (CIN) 2/3 diagnoses. DESIGN Preceding screening test results with computer-imaged, liquid-based cytology (LBC) and hrHPV results were analyzed for 2827 patients with histopathologic CIN 2/3 diagnoses. RESULTS Of 2827 patients with CIN 2/3 diagnoses, 2074 (73.4%) had system LBC findings within 4 months of CIN 2/3 diagnoses: high-grade squamous intraepithelial lesion (n = 862; 41.6%), low-grade squamous intraepithelial lesion (n = 464; 22.4%), atypical squamous cells of undetermined significance (n = 445; 21.5%), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (n = 288; 13.9%), and atypical glandular cells/adenocarcinoma in situ (n = 15; 0.7%). Of the 2827 patients, 1488 (52.6%) also had earlier system LBC results at more than 4 months to 3 years before CIN 2/3 diagnoses: one or more abnormal LBC results (n = 978; 65.7%), one or more negative LBC results (n = 911; 61.2%), both abnormal and negative LBC (n = 401; 26.9%). Of 807 patients with hrHPV cotest results within 4 months of CIN 2/3 diagnoses, 786 (97.4%) had hrHPV(+) results. Of 454 patients who also had earlier hrHPV results at more than 4 months to 3 years before CIN 2/3 diagnoses: 377 (83.0%) had one or more hrHPV(+) result, 110 (24.2%) had one or more hrHPV(-) result, and 33 (7.3%) had both positive and negative HPV results. CONCLUSION Patients with histopathologic CIN 2/3 had recent abnormal LBC results, most often, high-grade squamous intraepithelial lesions. Among cotested patients, 97.4% (786 of 807) tested hrHPV(+). However, a significant number of patients tested during an extended period of several years had earlier negative Papanicolaou or negative HPV test results, suggesting the recent development of some CIN 2/3 lesions and supporting the value of cotesting for enhanced detection of other developing, small, inaccessible, or nondiagnostic precursor lesions.
Comparative Study of 27-Gauge versus 25-Gauge Vitrectomy for the Treatment of Primary Rhegmatogenous Retinal Detachment

Purpose. To compare the vitrectomy time, clinical outcomes, and complications between 27-gauge (27-G) and 25-gauge (25-G) vitrectomy in patients with primary rhegmatogenous retinal detachment (PRRD). Methods. Prospective, nonrandomized, comparative, interventional study. Forty consecutive patients with PRRD were recruited. Twenty patients underwent the 27-gauge procedure and twenty patients had the 25-gauge procedure. The main outcome measure of the study was the actual vitrectomy time. Results. The mean duration of vitreous removal was 23.2 min (SD 6.5) with 27-G vitrectomy and 19.6 min (SD 7.3) with 25-G vitrectomy, resulting in a difference of 3.6 min (95% confidence interval (95%CI): −8.0 to 0.8 mins, p = 0.11). Mean logMAR visual acuity improved from 1.70 ± 1.18 preoperatively to 0.12 ± 0.14 at final postoperative visit (p < 0.001) in the 27-G group and from 1.52 ± 1.15 preoperatively to 0.22 ± 0.30 at final postoperative visit (p < 0.001) in the 25-G group. The anatomical success rate after a single operation was 90.0% and 85.0% in the 27-G and in the 25-G groups (p = 0.63), respectively. Intraoperative iatrogenic retinal breaks (IRBs) occurred in 2 eyes in the 27-G group and 1 eye in the 25-G group. Conclusions. Twenty-seven-gauge vitrectomy may be a safe and effective surgery for the treatment of PRRD.
In Search of the Physics: The Interplay of Experiment and Computation in Airframe Noise Research: Flap-Edge Noise

The LaRC investigative process for airframe noise has proven to be a useful guide for elucidation of the physics of flow-induced noise generation over the last five years. This process, relying on a close interplay between experiment and computation, is described and demonstrated here on the archetypal problem of flap-edge noise. Some detailed results from both experiment and computation are shown to illustrate the process, and a description of the multi-source physics seen in this problem is conjectured.
Currency demand stability in the presence of seasonality and endogenous financial innovation: Evidence from India

Based on the money-in-the-utility function, this paper intends to examine the stability of the currency demand function for India with real private consumption expenditure, tax-GDP ratio and deposit rate as explanatory variables by applying the seasonal cointegration technique developed by EGHL (1993) and HEGY (1990) for the period 1996:1 to 2014:4. The empirical findings show that there is absence of long-run cointegrationg relationship among the variables at the zero and annual frequency, however, there is evidence of a relationship among the variables at the biannual frequency. Moreover, the time-varying coefficient of deposit rate elasticity, used to test the Gurley-Shaw hypothesis, suggests that innovations in financial markets, especially improvements in the payment technology, raises the deposit rate elasticity, beginning from 2010 onward.
Determination of low-molecular-mass antioxidant concentrations in human respiratory tract lining fluids

ALBERT VAN DER VLIET,1,2 CHARLES A. O’NEILL,1,3 CARROLL E. CROSS,1 JOHN M. KOOSTRA,1 WILLIAM G. VOLZ,1 BARRY HALLIWELL,1,4 AND SAMUEL LOUIE1 1Division of Pulmonary/Critical Care Medicine, University of California, Davis Medical Center, Sacramento 95817; 2Center for Comparative Respiratory Biology and Medicine, Department of Internal Medicine, University of California, Davis 95616; 3Toxicology Department, Genentech, Inc., So. San Francisco, California 94080; and 4Pharmacology Group, International Antioxidant Research Centre, King’s College, London SW3 6LX, United Kingdom
An advanced system for the automatic classification of multitemporal SAR images

A novel system for the classification of multitemporal synthetic aperture radar (SAR) images is presented. It has been developed by integrating an analysis of the multitemporal SAR signal physics with a pattern recognition approach. The system is made up of a feature-extraction module and a neural-network classifier, as well as a set of standard preprocessing procedures. The feature-extraction module derives a set of features from a series of multitemporal SAR images. These features are based on the concepts of long-term coherence and backscattering temporal variability and have been defined according to an analysis of the multitemporal SAR signal behavior in the presence of different land-cover classes. The neural-network classifier (which is based on a radial basis function neural architecture) properly exploits the multitemporal features for producing accurate land-cover maps. Thanks to the effectiveness of the extracted features, the number of measures that can be provided as input to the classifier is significantly smaller than the number of available multitemporal images. This reduces the complexity of the neural architecture (and consequently increases the generalization capabilities of the classifier) and relaxes the requirements relating to the number of training patterns to be used for classifier learning. Experimental results (obtained on a multitemporal series of European Remote Sensing 1 satellite SAR images) confirm the effectiveness of the proposed system, which exhibits both high classification accuracy and good stability versus parameter settings. These results also point out that properly integrating a pattern recognition procedure (based on machine learning) with an accurate feature extraction phase (based on the SAR sensor physics understanding) represents an effective approach to SAR data analysis.
Pathogenicity and Transmission of Reticuloendotheliosis Virus Isolated from Endangered Prairie Chickens

Abstract The pathogenicity and transmission of a field isolate of reticuloendotheliosis virus (REV) was studied using an experimental model in Japanese quail. Oncogenicity was also evaluated after inoculations in chickens and turkeys. The original REV (designated APC-566) was isolated from Attwater's prairie chickens (Tympanuchus cupido attwateri), an endangered wild avian species of the southern United States. The transmissibility of the REV isolate was studied in young naive Japanese quail in contact with experimentally infected quail. Vertical transmission was not detected by virus isolation and indirect immunofluorescence. Seroconversion was detected in few contact quails, suggesting horizontal transmission. The APC-566 isolate induced tumors beginning at 6 wk of age in quails infected as embryos. Most of the tumors detected in Japanese quail were lymphosarcomas, and 81% of these neoplasias contained CD3+ cells by immunoperoxidase. REV APC-566 was also oncogenic in chickens and turkeys infected at 1 day of age, with tumors appearing as early as 58 days after infection in chickens and at 13 wk of age in turkeys. This study was conducted in part as an attempt to understand the potential for pathogenicity and transmission of REV isolated from endangered avian species.
Efficient high dimension data clustering using constraint-partitioning k-means algorithm

With the ever-increasing size of data, clustering of large dimensional databases poses a demanding task that should satisfy both the requirements of the computation efficiency and result quality. In order to achieve both tasks, clustering of feature space rather than the original data space has received importance among the data mining researchers. Accordingly, we performed data clustering of high dimension dataset using Constraint-Partitioning K-Means clustering algorithm which did not fit properly to cluster high dimensional data sets in terms of effectiveness and efficiency, because of the intrinsic sparse of high dimensional data and resulted in producing indefinite and inaccurate clusters. Hence, we carry out two steps for clustering high dimension dataset. Initially, we perform dimensionality reduction on the high dimension dataset using Principal Component Analysis as a preprocessing step to data clustering. Later, we integrate the Constraint-Partitioning K- Means clustering algorithm to the dimension reduced dataset to produce good and accurate clusters. The performance of the approach is evaluated with high dimensional datasets such as Parkinson's dataset and Ionosphere dataset. The experimental results showed that the proposed approach is very effective in producing accurate and precise clusters.
[Effect of Triptolide on TNFalpha-induced activation of NF-kappaB and expression of COX-2 and iNOS in human rheumatoid arthritis synovial fibroblasts].

OBJECTIVE To explore the effects of Triptolide (TP) on TNFalpha-induced cell proliferation and expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and their inducing products PGE2, NO in human rheumatoid arthritis synovial fibroblasts (RASF). METHODS Fibroblasts (RASF) were obtained from synovial tissue of patients with RA and were cultured in vitro. RASF were stimulated with TNFalpha(20 microg/L) in the presence or absence of TP(0 - 100 microg/L) for 20 h. The RASF proliferation was determined by (3)H-TdR incorporation, and the productions of PGE2 and NO in culture supernatants of RASF were detected with competitive ELISA and enzyme reduction of nitrate. Expressions of COX-2 and iNOS mRNA in RASF were analyzed by semi-quantitative RT-PCR. Expressions of COX-2 and iNOS protein were estimated by Western-blot method and cellular enzyme immunoassay in synovial fibroblasts. NF-kappaB activity in whole-cell extract of RASF was also measured by an ELISA-based method. RESULTS TP (>20 microg/L) down-regulated markedly TNFalpha-induced COX-2 and iNOS mRNA and protein expression, and their inducing products PGE2 and NO of synovial fibroblasts. This effect was positively correlated with TP concentrations. NF-kappaB activity in TNFalpha-stimulated synovial cells was suppressed profoundly by TP treatment (IC(50) approximately 35microg/L). The activity of NF-kappaB was correlated with the levels of COX-2 and iNOS expression in TNFalpha-stimulated RASF. No change was observed in proliferation of synovial cells after treatment of TP. CONCLUSION TP could significantly down-regulate TNFalpha-induced COX-2, iNOS expression and production of PGE2, NO in human RASF, which is associated with the suppression of NF-kappaB activity.