Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats

Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA), a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM)-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition, and activation of transforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.
The Relationship of Community Factors and Self-Efficacy with Adjustment and Well-being of First-Generation College Students

As of 2010, the National Center for Education Statistics (NCES) reported that first-generation college students (FGCS) composed almost 50% of the population within higher education (U.S. Department of Education, 2010). Consequently, this unique subgroup of college students are the focus of many post-secondary education studies to determine factors that contribute to their success (Mehta, Newbold, & O’Rourke, 2011; Owens, Lacey, Rawls, & Holbert-Quince, 2010; Pascarella, Wolniak, Pierson, & Terenzini, 2003; Prospero & Vohra-Gupta, 2007). Literature on FGCS calls for an examination of ecological (e.g., community factors) and individual factors relating to college adjustment and well-being as well as the role of general self-efficacy in these links (Dennis, Phinney, & Chuateco, 2005; Plybon, Edwards, Butler, Belgrave, & Allison, 2003). Sampling ethnic and racial minority FGCS and White FGCS at various U.S. American institutions, the present study examined the direct and indirect relations between community factors and college student adjustment and personal well-being (i.e., life satisfaction), through general self-efficacy. Findings suggest that the relations between community factors, selfefficacy, college adjustment, and life satisfaction differ for ethnic and racial minority FGCS and White FGCS. Implications are provided for the design of more effective counseling interventions and higher education programming for ethnically and racially diverse FGCS.
Bootstrap Decision Making for Polygraph Examinations

Abstract : The authors examined human numerical evaluation, discriminant analysis, and a bootstrap approach to decision making in the psychophysiological detection of deception with the control question test. The data for these analyses were obtained from the Utah Cooperative Working Group Database and consisted of 100 innocent and 100 guilty subjects of mock crime experiments. They found statistically equivalent performance for the three approaches. However, it should be noted that the human evaluators used in this study were not representative of the average polygraph examiner, and the human evaluation data reported here are likely to have substantially overestimated the accuracy of human numerical evaluation in the field. Taken in that context, the performance of the statistical classifiers should be viewed very favorably. In absolute terms, the bootstrap approach outperformed the other two approaches. As compared to discriminant analysis, the bootstrap has much to recommend it. It avoids the restrictive mathematical assumptions of discriminant analysis, and since it is not tied to any empirical standardization sample, the bootstrap approach is likely to be widely generalizable. The authors conclude that statistical decision making has come of age in the detection of deception and should see universal applications in the field in the near future.
Molecular Basis for Kv1.5 Channel Block

Kv1.5 channels conduct the ultrarapid delayed rectifier current (IKur) that contributes to action potential repolarization of human atrial myocytes. Block of these channels has been proposed as a treatment for atrial arrhythmias. Here we report a novel and potent inhibitor of Kv1.5 potassium channels, N-benzyl-N-pyridin-3-yl-methyl-2-(toluene-4-sulfonylamino)-benzamide hydrochloride (S0100176), which exhibits features consistent with preferential block of the open state. The IC50 of S0100176 for Kv1.5 expressed in Xenopus oocytes was 0.7 μm. Ala-scanning mutagenesis within the pore helix and the S6 segment, regions that form the walls of the central cavity, was combined with voltage clamp analysis to identify point mutations that altered drug affinity. This approach identified Thr-479, Thr-480, Val-505, Ile-508, and Val-512 as the most important residues for block by S0100176. Mutations of these key residues to Ala or other amino acids caused marked changes in the IC50 of S0100176 (p < 0.01). For example, the IC50 of S0100176 increased 362-fold for T480A, 26-fold for V505A, 150-fold for I508A, and 99-fold for V512A. We used modeling to dock S0100176 into the inner cavity of a Kv1.5 pore homology model that was generated based on the crystal structure of KcsA. The docking predicted that the five residues identified by the Ala scan were positioned less than 4.5 Å from the compound. Based on the homology models, the positions of the five amino acids identified to interact with S0100176 face toward the central cavity and overlap with putative binding sites for other blockers and voltage-gated potassium channels.
Anterior medial temporal lobe in human cognition: Memory for fear and the unexpected

Introduction. To survive, an organism must remember occurrences of value in its environment. These include those that pose a threat to survival, novel or unexpected stimuli, or a general class of stimuli that represent punishment or reward. There is substantial evidence that memory for novel and emotionally salient events is enhanced relative to familiar or emotionally neutral events. Methods. We present human functional magnetic resonance imaging (fMRI) experiments that address the neurobiological processes underlying upregulation of memory for novel or emotional events. Results. Enhanced memory for novel or unexpected stimuli is mediated by anterior hippocampus, whereas increased memory for emotional stimuli is mediated by a β‐adrenergic‐dependent modulation of amygdala‐hippocampal interactions. We introduce a hypothesis that medial temporal connectivity with autonomic control centres may be central to this memory enhancement. Conclusion. Enhanced memory for stimuli that are of adaptive importance to survival is mediated by the anterior medial temporal lobe and effected via connections with the autonomic system.
Tracking of moving wireless LAN terminals

The ability to locate and track mobile terminals in wireless communication networks is an essential prerequisite for the deployment of context-aware services and pervasive systems, in indoor environments the most popular approach to this problem is to calculate terminal positions based on radio signal strength samples taken from a deployed wireless LAN infrastructure. This paper proposes a probabilistic scheme for tracking mobile terminals. The scheme has proven to be highly robust and accurate when locating stationary terminals, yet moving terminals pose different requirements. Hence, the proposed scheme has been adapted to the problem of tracking terminals in indoor environments. Performance measurements are presented comparing the accuracy of the proposed scheme to a simple deterministic pattern matching algorithm.
Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients

AbstractAim:To investigate whether the CYP3A5*3 polymorphism would affect cyclosporine A (CsA) metabolism in Chinese renal transplant patients.Methods:The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA). The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio (MR) values were calculated.Results:The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous (*3*3) and heterozygous variants (*1 *3). However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows: 0.92±0.62 for CYP3A5*3/ *3 (n=14), 0.99±0.51 for CYP3A5*1/*3 (n=15), and 1.45±0.62 for CYP3A5*1/*1 (n=9), respectively. Post hoc comparisons showed that only the MR values between the CYP3A5*3/*3 group and the CYP3A5*1/*1 group were significantly different.Conclusion:The CYP3A5*3 polymorphism exerted little effect on cyclosporine metabolism. The MR may be a more accurate indicator for therapeutic drug monitoring, considering its integrated information on body exposure of both parent drugs and metabolites.
Metaphors Ubiquitous in Computer and Internet Terminologies

Computer and Internet sciences are developing so rapidly that they are pervasive in every aspect of our society and life, which forms computer and Internet culture. Concomitant with this computer and Internet culture is the large amount of computer and Internet metaphorical language. This thesis would like to employ the contemporary cognitive linguistic theories of metaphor to make a systematic analysis of the metaphors ubiquitous in computer and Internet terminologies. After that, it probes into the coherence of the metaphors, which has a great impact on the language production of human being in their everyday life.
Effect of E(sev) and Su(Raf) Hsp83 Mutants and Trans-heterozygotes on Bristle Trait Means and Variation in Drosophila melanogaster

The Hsp90 protein encoded by the Hsp83 gene is required for the development of many traits in Drosophila. Hsp83 is also thought to play a role in the expression of phenotypic and genetic variability for subsequent selection and evolutionary change. Here we examine the impact of different E(sev) and Su(Raf) Hsp83 mutants on means and phenotypic variances of invariant and variable bristle traits. One of the mutants influenced the normally invariant thoracic bristle number, while none affected invariant scutellar bristle number. E(sev) alleles consistently influenced variable bristle traits while there were fewer effects of the Su(Raf) alleles. For the variable traits, none of the Hsp83 alleles had any effect on phenotypic variance, environmental variance, or developmental stability of the bristle traits. When alleles were combined in trans-heterozygotes, there were both cumulative and complementary effects on thoracic and variable bristle trait numbers, depending on the allelic combination. Overall, the results suggest that Hsp83 mutants do not have detectable effects on the phenotypic or environmental variance of bristle traits and that complementation of E(sev) and Su(Raf) Hsp83 mutants can extend to thoracic bristles as well as previously reported effects on viability. Some allelic combinations lead to more severe effects on variable bristle trait means than do single Hsp83 mutations.
Seasonal variability of trace metals in the Lena River and the southeastern Laptev Sea : Impact of the spring freshet

The distribution of dissolved and particulate trace metals (Fe, Mn, Cu, Ni, Zn, and Pb) was studied for the first time during the spring high flow period of the Lena River (Arctic Siberia). The results show that concentrations of dissolved metals in the river Lena during the spring high flow in June 1996 (spring freshet) were significantly higher than those reported for the rest of the year. For example the measured average concentration of dissolved Fe (6349F2122 nM) during the high flow is approximately 7 times higher than previously published concentrations measured during the summer months. Dissolved Fe concentrations in the freshwater (salinityb1) are positively correlated with the amount of suspended particulate matter (SPM) ( p b0.01), but negatively correlated with the Fe concentrations in SPM ( p b0.01). The data showed that the aluminium-normalized concentrations of particulate Fe, Mn, Pb, Ni, and Zn in the freshwater are negatively correlated with SPM. This suggests that the mobilization of metals from suspended particulate matter is the driving force for the observed high concentrations of dissolved Fe, Mn, Zn and Pb in the water of the Lena River during the spring freshet. During the high flow period in June about 35% of the total annual flow of the river Lena flows into the Laptev Sea. Previously published metal budgets for the river Lena that did not incorporate data from the spring high flow period, therefore, underestimate the fluxes of dissolved trace metals from the Siberian rivers to the Arctic Ocean. For instance, the estimated input of dissolved Fe in June 1996 is approximately 4.5 times higher than the average annual dissolved Fe input calculated on the basis of summer data. The results of this study demonstrate that the previous evaluations of the trace metal flux of the Lena river–which are based on data obtained from August to October–may underestimate the total riverine input of dissolved trace metals to the Arctic Ocean. D 2005 Elsevier B.V. All rights reserved.
Monoclonal Antibodies to the V2 Domain of MN-rgp120: Fine Mapping of Epitopes and Inhibition of α4β7 Binding

Background Recombinant gp120 (MN-rgp120) was a major component of the AIDSVAX B/E vaccine used in the RV144 trial. This was the first clinical trial to show that vaccination could prevent HIV infection in humans. A recent RV144 correlates of protection study found that protection correlated with the presence of antibodies to the V2 domain. It has been proposed that antibodies to the α4β7 binding site in the V2 domain might prevent HIV-1 infection by blocking the ability of virions to recognize α4β7 on activated T-cells. In this study we investigated the specificity of monoclonal antibodies (MAbs) to the V2 domain of MN-rgp120 and examined the possibility that these antibodies could inhibit the binding of MN-rgp120 to the α4β7 integrin. Methodology/Principal Findings Nine MAbs to the V2 domain were isolated from mice immunized with recombinant envelope proteins. The ability of these MAbs to inhibit HIV infection, block the binding of gp120 to CD4, and block the binding of MN-rgp120 to the α4β7 integrin was measured. Mutational analysis showed that eight of the MAbs recognized two immunodominant clusters of amino acids (166–168 and 178–183) located at either end of the C strand within the four-strand anti-parallel sheet structure comprising the V1/V2 domain. Conclusions/Significance These studies showed that the antigenic structure of the V2 domain is exceedingly complex and that MAbs isolated from mice immunized with MN-rgp120 exhibited a high level of strain specificity compared to MAbs to the V2 domain isolated from HIV-infected humans. We found that immunization with MN-rgp120 readily elicits antibodies to the V2 domain and some of these were able to block the binding of MN-rgp120 to the α4β7 integrin.
Relation between circulating angiotensin II type 1 receptor agonistic autoantibodies and soluble fms-like tyrosine kinase 1 in the pathogenesis of preeclampsia.

CONTEXT Placental and circulatory soluble fms-like tyrosine kinase 1 (sFlt1) has proven to be elevated in pregnant women with preeclampsia, a disease characterized by hypertension, proteinuria, and endothelial dysfunction. Recent studies also demonstrated an autoantibody against the angiotensin II type 1 (AT1) receptor (AT1-AA) in that disease. OBJECTIVE Both factors are discussed as key players in the etiology of preeclampsia. However, it has not yet been clarified whether these two circulating factors correlate and whether synergy determines the severity of pathology. DESIGN AT1-AA was retrospectively determined by a bioassay and sFlt1 by an ELISA. PATIENTS Serum from second-trimester pregnancies with normal or abnormal uterine perfusion and in women at term with or without pregnancy pathology was analyzed. RESULTS Most of the preeclamptic patients were characterized by high sFlt1 levels and the presence of AT1-AA, although the agonistic effects of the antibody did not correlate with the sFlt1 concentrations (P = 0.85). Although AT1-AA was also detected in second-trimester pregnancies evidencing abnormal uterine perfusion without later pathology, sFlt1 was not significantly elevated in these pregnancies, compared with those with normal uterine perfusion. However, whereas women with abnormal perfusion and later pregnancy pathology did not differ in AT1-AA, compared with those with normal outcome, sFlt1 was significantly increased. Again, the two factors did not correlate (P = 0.15). CONCLUSIONS We conclude that AT1-AA bioactivity and sFlt1 concentrations do not correlate, are not mutually dependent, and are thus probably involved in distinct pathogenetic mechanisms. Both factors in combination may not be causative for the early impaired trophoblast invasion and pathological uterine perfusion.
Biomarker-based predictive models for prognosis in amyotrophic lateral sclerosis.

IMPORTANCE Although median survival in amyotrophic lateral sclerosis (ALS) is 2 to 4 years, survival ranges from months to decades, creating prognostic uncertainty. Strategies to predict prognosis would benefit clinical management and outcomes assessments of clinical trials. OBJECTIVE To identify biomarkers in plasma and cerebrospinal fluid (CSF) of patients with ALS that can predict prognosis. DESIGN, PARTICIPANTS, AND SETTING We conducted a retrospective study of plasma (n = 29) and CSF (n = 33) biomarkers identified in samples collected between March 16, 2005, and August 22, 2007, from patients with ALS at an academic tertiary care center. Participants included patients who were undergoing diagnostic evaluation in the neurology outpatient clinic and were eventually identified as having definite, probable, laboratory-supported probable, or possible ALS as defined by revised El-Escorial criteria. All were white and none had a family history of ALS. Clinical information extended from initial presentation to death. Genotyping for hemochromatosis (HFE) gene status was performed. Multiplex and immunoassay analysis of plasma and CSF was used to measure levels of 35 biomarkers. Statistical modeling was used to identify biomarker panels that could predict total disease duration. MAIN OUTCOMES AND MEASURES Total disease duration, defined as the time from symptom onset to death, was the main outcome. The hypothesis being tested was formulated after data collection. RESULTS Multivariable models for total disease duration using biomarkers from plasma, CSF, and plasma and CSF combined incorporated 7, 6, and 6 biomarkers to achieve goodness-of-fit R2 values of 0.769, 0.617, and 0.962, respectively. After classification into prognostic categories, actual and predicted values achieved moderate to good agreement, with Cohen κ values of 0.526, 0.515, and 0.930 for plasma, CSF, and plasma and CSF combined models, respectively. Inflammatory biomarkers, including select interleukins, growth factors such as granulocyte colony-stimulating factor, and l-ferritin, had predictive value. CONCLUSIONS AND RELEVANCE This study provides proof-of-concept for a novel multivariable modeling strategy to predict ALS prognosis. These results support unbiased biomarker discovery efforts in larger patient cohorts with detailed longitudinal follow-up.
Active Learning From Stream Data Using Optimal Weight Classifier Ensemble

In this paper, we propose a new research problem on active learning from data streams, where data volumes grow continuously, and labeling all data is considered expensive and impractical. The objective is to label a small portion of stream data from which a model is derived to predict future instances as accurately as possible. To tackle the technical challenges raised by the dynamic nature of the stream data, i.e., increasing data volumes and evolving decision concepts, we propose a classifier-ensemble-based active learning framework that selectively labels instances from data streams to build a classifier ensemble. We argue that a classifier ensemble's variance directly corresponds to its error rate, and reducing a classifier ensemble's variance is equivalent to improving its prediction accuracy. Because of this, one should label instances toward the minimization of the variance of the underlying classifier ensemble. Accordingly, we introduce a minimum-variance (MV) principle to guide the instance labeling process for data streams. In addition, we derive an optimal-weight calculation method to determine the weight values for the classifier ensemble. The MV principle and the optimal weighting module are combined to build an active learning framework for data streams. Experimental results on synthetic and real-world data demonstrate the performance of the proposed work in comparison with other approaches.
The Fundamental Role of Pirouettes in Caenorhabditis elegans Chemotaxis

To investigate the behavioral mechanism of chemotaxis inCaenorhabditis elegans, we recorded the instantaneous position, speed, and turning rate of single worms as a function of time during chemotaxis in gradients of the attractants ammonium chloride or biotin. Analysis of turning rate showed that each worm track could be divided into periods of smooth swimming (runs) and periods of frequent turning (pirouettes). The initiation of pirouettes was correlated with the rate of change of concentration (dC/dt) but not with absolute concentration. Pirouettes were most likely to occur when a worm was heading down the gradient (dC/dt < 0) and least likely to occur when a worm was heading up the gradient (dC/dt > 0). Further analysis revealed that the average direction of movement after a pirouette was up the gradient. These observations suggest that chemotaxis is produced by a series of pirouettes that reorient the animal to the gradient. We tested this idea by imposing the correlation between pirouettes and dC/dt on a stochastic point model of worm motion. The model exhibited chemotaxis behavior in a radial gradient and also in a novel planar gradient. Thus, the pirouette model ofC. elegans chemotaxis is sufficient and general.