Miracle-dz/UniFAR-FTUs huggingface dataset:
Genes Associated with Prostate Cancer Are Differentially Expressed in African American and European American Men

Background: Despite more aggressive screening across all demographics and gradual declines in mortality related to prostate cancer (PCa) in the United States, disparities among populations persist. A substantial proportion of African American men (AAM) have a higher overall incidence, earlier age of onset, increased proportion of clinically advanced disease, and increased bone metastases and mortality from PCa compared to European American men (EAM). Limited early evidence indicates that underlying causes for disparities may be observed in tumor-specific gene expression programs. Methods: This study used microarray-based methods to measure expression levels for 517 genes that were previously associated with PCa in archived formalin-fixed paraffin embedded (FFPE) specimens; testing the hypothesis that gene expression features of functional consequence to cancer distinguish PCa from AAM and EAM. A t test was conducted comparing AAM to EAM expression levels for each probe on the array. Results: Analysis of 639 tumor samples (270 AAM, 369 EAM) showed that 95 genes were overexpressed specifically in PCa from AAM relative to EAM and 132 were overexpressed in PCa from EAM relative to AAM. Furthermore, systems-level analyses highlight the relevant signaling pathways and functions associated with the EAM- or AAM-specific overexpressed gene sets, for example, inflammation and lipid metabolism. Conclusions: Results here bring further understanding to the potential for molecular differences for PCa in AAM versus EAM. Impact: The results support the notion that therapeutic benefits will be realized when targeted treatments are designed to acknowledge and address a greater spectrum of PCa subtypes and molecular distinctions. Cancer Epidemiol Biomarkers Prev; 22(5); 891–7. ©2013 AACR.
Real-Time Optimal Control of a 3-Phase PMSM in 2-Phase Degraded Mode

This paper aims to optimize real-time control for the degraded mode of a fault-tolerant power architecture but not the fault detection and isolation procedure itself. Such power architecture is dedicated to electric vehicles in which it performs the three following essential functions: traction, battery charging, and electric-grid assistance. For safety reasons, in the degraded mode, power control is limited to the traction mode. Thus, for a given torque, the proposed innovative strategy uses a novel current/voltage transform that leads to efficient real-time control of the torque. The key idea is to drive the current without a priori restrictions on its waveform, while minimizing Joule losses, i.e., the effective value of the current. It has been validated on a laboratory test bench. The studied system is based on a three-phase open-end-winding synchronous machine powered by an inverter with three full H-bridges. The last section of the paper analyzes the comparison between the classic sinusoidal current waveforms and the proposed sinusoidal current waveforms while operating on the two remaining motor phases. It results in a 14% increase of the torque produced by the permanent-magnet machine under test and a 14% decrease of the global system losses in traction mode. As a result, the new control strategy enhances traction performance in degraded mode and increases electric-vehicle autonomy in a postfailure condition.
Molecular Diagnosis of Cystic Fibrosis: Comparison of Four Analytical Procedures

Abstract We compared the analytical accuracy, times, costs and the detection rate of four procedures for the molecular analysis of cystic fibrosis (CF). DNA from 127 subjects bearing different genotypes was tested by denaturating gradient gel electrophoresis followed by sequencing (reference procedure) and, for comparison, by ASO dot-blot (in-house), reverse dot-blot (Innogenetics), ARMS (Zeneca Diagnostics) and OLA-PCR (PE Applied Biosystem). To assess inter-observer variability, all samples were tested twice. To evaluate intra- and between-series variability, two samples were tested twice in each series. All the procedures yielded reproducible results and assigned the correct genotype to each sample. ASO dot-blot is the cheapest procedure but has the longest analytical time (>24 h) and uses radioactive labeling. It can be adapted to analyze peculiar mutations in specific ethnic groups. ARMS from Zeneca Diagnostics is rapid (4 h), easy to perform, but, except for the ∆F508 mutation, does not distinguish the homozygote from the heterozygote genotype. It could be used for carrier analysis in families with known mutations. OLA-PCR has the highest detection rate in most ethnic groups, is automated for capillary electrophoresis but requires a high level of operator expertise: it is suitable when collected series of samples are analyzed from large patient cohorts. Reverse dot-blot is easy to perform and can be semiautomated: it can be used as first-line screening test. Given the heterogeneity of CF mutations, commercial kits should be developed to analyze mutations peculiar to specific ethnic groups.
Variation of the Ribosomal Operon 16S-23S Gene Spacer Region in Representatives of Salmonella enterica Subspecies

ABSTRACT The 16S-23S spacer regions of two ribosomal operons (rrnA and rrnE) have been sequenced in seven representatives of the Salmonella entericasubspecies. Isolated nucleotide substitutions were found at the same sites as in Escherichia coli but the number of polymorphic sites was much larger, as could be expected for a more heterogeneous species. Still, as in E. coli, most of the variation found was due to insertions and/or deletions affecting blocks of nucleotides generally located at equivalent regions of the putative secondary structure for both species. Isolated polymorphic sites generated phylogenetic trees generally consistent with the subspecies structure and the accepted relationships among the subspecies. However, the sequences of rrnE put subspecies I closer to E. coli K-12 than to the other S. enterica subspecies. The distribution of polymorphisms affecting blocks of nucleotides was much more random, and the presence of equivalent sequences in distantly related subspecies, and even in E. coli, could reflect relatively frequent horizontal transfer. The smallest 16S-23S spacers in other genera of the family Enterobacteriaceaewere also sequenced. As expected, the level of variation was much larger. Still, the phylogenetic tree inferred is consistent with those of 16S rRNA or housekeeping genes.
Motor Protein Function in Skeletal Muscle—A Multiple Scale Approach to Contractility

We present an approach to skeletal muscle contractility and its regulation over different scales ranging from biomechanical studies in intact muscle fibers down to the motility and interaction of single motor protein molecules. At each scale, shortening velocities as a measure for weak cross-bridge cycling rates are extracted and compared. Experimental approaches include transmitted light microscopy, second harmonic generation imaging of contracting myofibrils, and fluorescence microscopy of single molecule motility. Each method yields image sequences that are analyzed with automated image processing algorithms to extract the contraction velocity. Using this approach, we show how to isolate the contribution of the motor proteins actin and myosin and their modulation by regulatory proteins from the concerted action of electro-mechanical activation on a more complex cellular scale. The advantage of this approach is that averaged contraction velocities can be determined on the different scales ranging from isolated motor proteins to sarcomere levels in myofibrils and myofibril arrays within the cellular architecture. Our results show that maximum shortening velocities during in situ electrical activation of sarcomere contraction in intact single muscle cells can substantially deviate from sliding velocities obtained in oriented in vitro motility assays of isolated motor proteins showing that biophysical contraction kinetics not simply translate linearly between contractility scales. To adequately resolve the very fast initial mechanical activation kinetics of shortening at each scale, it was necessary to implement high-speed imaging techniques. In the case of intact fibers and single molecule motility, we achieved a major increase in temporal resolution up to frame rates of 200-1000 fps using CMOS image sensor technology. The data we obtained at this unprecedented temporal resolution and the parameters extracted can be used to validate results obtained from computational models of motor protein interaction and skeletal muscle contractility in health and muscle disease. Our approach is feasible to explain the possible underlying mechanisms that contribute to different shortening velocities at different scales and complexities.
Creatine enhances oxygen uptake and performance during alternating intensity exercise.

PURPOSE The main purpose of the present study was to measure the total oxygen consumed, accumulation of blood metabolites, and performance during alternating intensity exercise before and after a period of creatine (Cr) loading in well-trained humans. METHODS Fourteen males were randomly assigned to two groups of seven males and were tested before and after 5 d of placebo (PL) or Cr monohydrate (CR) loading (20 g x d(-1)). Oxygen uptake was measured using a breath-by-breath system during bicycle exercise alternating every 3 min between bouts at 30%(-30%) and 90% (-90%) of the maximal power output to exhaustion. Blood samples were also obtained at rest, before the end of each cycling load, at exhaustion, and 5-min postexercise. RESULTS The oxygen consumed during 1-90% (5.08 +/- 0.39 L) and 2-90% (5.32 +/- 0.30 L) was larger after CR (5.67 +/- 0.34 and 5.78 +/- 0.35 L, P < 0.01 and P < 0.05, respectively). Blood ammonia accumulation at the end of 1-90% (23.1 +/- 6.5 micromol x L(-1)) and 3-30% (64.7 +/- 15.2 micromol x L(-1)) was lower after CR (P < 0.05), whereas plasma uric acid accumulation was lower at exhaustion (P < 0.05) and 5-min postexercise (P < 0.01). Time to exhaustion increased (P < 0.05) from 29.9 +/- 3.8 to 36.5 +/- 5.7 min after CR, whereas it remained the same after PL. CONCLUSIONS The results indicate that Cr feeding increases the capacity of human muscle to perform work during alternating intensity contraction, possibly as a consequence of increased aerobic phosphorylation and flux through the creatine kinase system.
Development and validation of Chinese version of female sexual function index in a Chinese population-a pilot study.

INTRODUCTION Female sexual dysfunction (FSD) is a prevalent problem that has been continuously overlooked in mainland China. An assessment instrument for FSD is urgently needed. AIM To develop and validate the Chinese version of the Female Sexual Function Index (CVFSFI) to assess FSD in China. METHODS A total of 328 women (20-65 years old) participated in this study. The CVFSFI was developed through the procedures of translation, back translation, revision by research team, and pilot study. After an interview for clinical diagnosis of FSD based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria, all participants completed the CVFSFI for a validation study. Eighty-three women completed CVFSFI again 3-4 weeks after the first visit. Test-retest reliability was determined by Pearson product-moment correlations. Internal consistency reliability was estimated with Cronbach's alpha coefficient. Construct validity was evaluated by principal component analysis using varimax rotation. Discriminant validity was assessed with between-groups analysis of variance. MAIN OUTCOME MEASURES Including the reliability and the validity of the CVFSFI and its domains. RESULTS A total of 172 women (52.4%) met the DSM-IV-TR criteria for diagnosis of sexual dysfunction and were included in the FSD group, while 156 (47.6%) women without FSD were included in the control group. We showed that the overall test-retest reliability coefficients were high for total CVFSFI and each domain (r at least 0.69) and the internal consistency reliability of CVFSFI was within the acceptable range (Cronbach's alpha values: from 0.69 to 0.94). Moreover, the principal component analysis with varimax rotation produced six-factor structure similar to the original FSFI. We found significant differences in both total and domain scores between FSD and control groups, demonstrating a good discriminant validity of CVFSFI. CONCLUSION The CVFSFI is a reliable and valid questionnaire, which can be used in the assessment of FSD among Chinese women.
Functions of DNA methyltransferase 3‐like in germ cells and beyond

DNA methyltransferase 3‐like (DNMT3L) is one of the key players in de novo DNA methylation of imprinting control elements and retrotransposons, which occurs after genome‐wide epigenetic erasure during germ cell development. In this review, we summarise the biochemical properties of DNMT3L and discuss the possible mechanisms behind DNMT3L‐mediated imprinting establishment and retrotransposon silencing in germ cells. We also discuss possible connections between DNMT3L and non‐coding RNA‐mediated epigenetic remodelling, the roles of DNMT3L in germ cell development and the implications in stem cell and cancer research.
An anatomical, histopathological, and molecular biological function study of the fascias posterior to the interperitoneal colon and its associated mesocolon: their relevance to colonic surgery

The study aim was to explore the anatomy, histopathology, and molecular biological function of the fascias posterior to the interperitoneal colon and its mesocolon to provide information for improving complete mesocolic excision. To accomplish this aim, we performed intraoperative observations in 60 interperitoneal colon‐cancer patients accepted for complete mesocolic excision and conducted local anatomy observations for five embalmed cadavers. An additional two embalmed child cadaver specimens were studied with large slices and paraffin sections. Ten of the 60 patients were examined with a lymph node tracer technique in vivo, while fresh specimens from these patients were assessed by histopathological examination and transwell cell migration assays in vitro. The anatomical and histopathological findings showed that the fascias posterior to the interperitoneal colon and its associated mesocolon were composed of two independent layers: the visceral and parietal fascias. These two fascias were primarily composed of collagen fibers, with the parietal fascia containing a small amount of muscle fiber. The in vivo test showed that the visceral fascia surrounded the colon and its associated mesocolon, including vessels and lymphatics, and that it had no lymphatic flow through it into the rear tissues. Moreover, the in vitro assays showed the visceral fascia was able to block tumor cell migration. Although many surgical scholars have known of the existence of fascia tissue posterior to the intraperitoneal colon, the detailed structure has been ignored and been unclear. As shown by our findings, the visceral and parietal fascias are truly formed structures that have not been previously reported. A thorough understanding of fascial structures and the function of the visceral fascia barrier in blocking tumor cells will facilitate surgeons when performing high‐quality complete mesocolic excision procedures.
Induction of CD8+ cytotoxic T lymphocytes by immunization with syngeneic irradiated HIV-1 envelope derived peptide-pulsed dendritic cells.

Based on the evidence that CD8+ cytotoxic T cells (CTL) precursors do not appear to distinguish between virus-infected cells and viral peptide-pulsed syngeneic cells, we have developed methods for priming class I MHC molecule restricted CD8+ CTL with such peptides without using any adjuvant. We were able to prime in vivo such CTL immunity lasting at least 6 months with a single i.v. injection of syngeneic 2200-3300 rad irradiated peptide-pulsed spleen cells, and even more efficiently with a very small number of irradiated class II MHC molecule expressing splenic dendritic cells (DC). No foreign serum source was necessary during the pulsing. Interestingly, we could not generate significant CTL activity with unirradiated or low dose (< 1100 rad) irradiated spleen cells. Because even purified DC required irradiation for optimal activity, because unirradiated B cells did not significantly inhibit the immunization with DC, and because B cell depletion did not substitute for irradiation, we believe that the effect of irradiation is more to determine homing of the cells than to eliminate interference by B cells. Intravenous immunization was much more effective than s.c. or i.p. immunization. CTL generated by this method could kill both peptide-pulsed syngeneic targets and targets endogenously expressing the whole gp160 gene. Moreover, we found that we could prime CD8+ CTL with the minimal 10-residue core peptide (RGPGRAFVTI) for optimal presentation by class I MHC molecules as efficiently as the original p18. These results suggested that DC bearing antigenic peptide may prime antigen-specific CD8+ CTL in vivo. These results offer useful information for development of synthetic peptide vaccines and immunotherapy.
Efficient Graph Similarity Search in External Memory

Many real-world applications, such as bioinformatics, data mining, pattern recognition, and social network analysis, benefit from efficient solutions for the graph similarity search problem. Existing methods have limited scalability when they handle the large graph databases, for example, those with millions or billions of graphs that cannot fit in main memory. In this paper, we study the problem of graph similarity search under the graph edit distance constraint in external memory. We present an efficient framework for arbitrary <inline-formula> <tex-math notation="LaTeX">$q$ </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">${gram}$ </tex-math></inline-formula>-based representations of a graph. Specifically, we propose a <inline-formula> <tex-math notation="LaTeX">$q$ </tex-math></inline-formula>-<italic>gram</italic> matrix index stored in hybrid layout in external memory to achieve efficient query processing, by converting the <inline-formula> <tex-math notation="LaTeX">$q$ </tex-math></inline-formula>-<italic>gram</italic> counting filter into a sparse matrix-vector multiplication problem. Furthermore, we also boost the query performance by transforming the global filter to a 2-D query rectangle, which allows us to perform a query in a reduced region, significantly reducing the number of query I/Os in practice. Extensive experiments on real data sets confirm that 1) our method can compete with the state-of-the-art in-memory methods in index size and filtering ability, and outperform them on scalability of coping with the PubChem data set including 25 million chemical structure graphs and 2) compared with the popular <inline-formula> <tex-math notation="LaTeX">$q$ </tex-math></inline-formula>-<italic>gram</italic>-based external inverted index, our external index structure needs much fewer number of query I/Os on the PubChem data set.
Molecular Mechanisms Underlying Ketamine-mediated Inhibition of Sarcolemmal Adenosine Triphosphate-sensitive Potassium Channels

Background: Ketamine inhibits adenosine triphosphate-sensitive potassium (KATP) channels, which results in the blocking of ischemic preconditioning in the heart and inhibition of vasorelaxation induced by KATP channel openers. In the current study, the authors investigated the molecular mechanisms of ketamine’s actions on sarcolemmal KATP channels that are reassociated by expressed subunits, inwardly rectifying potassium channels (Kir6.1 or Kir6.2) and sulfonylurea receptors (SUR1, SUR2A, or SUR2B). Methods: The authors used inside-out patch clamp configurations to investigate the effects of ketamine on the activities of reassociated Kir6.0/SUR channels containing wild-type, mutant, or chimeric SURs expressed in COS-7 cells. Results: Ketamine racemate inhibited the activities of the reassociated KATP channels in a SUR subtype-dependent manner: SUR2A/Kir6.2 (IC50 = 83 &mgr;m), SUR2B/Kir6.1 (IC50 = 77 &mgr;m), SUR2B/Kir6.2 (IC50 = 89 &mgr;m), and SUR1/Kir6.2 (IC50 = 1487 &mgr;m). S-(+)-ketamine was significantly less potent than ketamine racemate in blocking all types of reassociated KATP channels. The ketamine racemate and S-(+)-ketamine both inhibited channel currents of the truncated isoform of Kir6.2 (Kir6.2&Dgr;C36) with very low affinity. Application of 100 &mgr;m magnesium adenosine diphosphate significantly enhanced the inhibitory potency of ketamine racemate. The last transmembrane domain of SUR2 was essential for the full inhibitory effect of ketamine racemate. Conclusions: These results suggest that ketamine-induced inhibition of sarcolemmal KATP channels is mediated by the SUR subunit. These inhibitory effects of ketamine exhibit specificity for cardiovascular KATP channels, at least some degree of stereoselectivity, and interaction with intracellular magnesium adenosine diphosphate.
Combined effects of ultraviolet‐B radiation and food shortage on the sensitivity of the Antarctic amphipod Paramoera walkeri to copper

Investigations on the combined effects of ultraviolet (UV)‐B radiation and anthropogenic toxicants have focused primarily on the chemical interactions between UV‐B and organic compounds. Only a few studies have examined whether exposure to UV‐B changes sensitivity to toxicants. This question is addressed in a laboratory study using the common shoreline Antarctic amphipod Paramoera walkeri and exposure to environmentally realistic levels of copper, UV‐B radiation, and food shortage. Exposure to copper for 21 d in the absence of any additional stressors (food present, no UV‐B) showed a lowest observable effective concentration (LOEC) of greater than 100 μg Cu/L. Exposure to copper and UV‐B in combination, with no shortage of food, resulted in a LOEC of 45 μg Cu/L. When exposed to copper and UV‐B, with shortage of food, a LOEC of 3 μg Cu/L was recorded. Hence, the combination of environmental stress from exposure to UV‐B radiation and shortage of food increases the sensitivity of P. walkeri to copper more than 30‐fold. Increased metabolic energy requirements for defense mechanisms in response to toxicants and UV‐B are discussed as possible explanations. It is concluded that consideration of environmental stressors in combination with toxicants increases the accuracy of ecological risk assessments of toxicants and should be part of the process for developing guidelines for ecologically acceptable concentrations of contaminants in the environment.