gebhart/patrepeval huggingface dataset:
Serum C-reactive protein metabolite (CRPM) is associated with incidence of contralateral knee osteoarthritis (2021)

The heterogeneous nature of osteoarthritis (OA) and the need to subtype patients is widely accepted in the field. The biomarker CRPM, a metabolite of C-reactive protein (CRP), is released to the circulation during inflammation. Blood CRPM levels have shown to be associated with disease activity and response to treatment in rheumatoid arthritis (RA). We investigated the level of blood CRPM in OA compared to RA using data from two phase III knee OA and two RA studies (N = 1591). Moreover, the association between CRPM levels and radiographic progression was investigated. The mean CRPM levels were significantly lower in OA (8.5 [95% CI 8.3-8.8] ng/mL, n = 781) compared to the RA patients (12.8 [9.5-16.0] ng/mL, n = 60); however, a significant subset of OA patients (31%) had CRPM levels (≥ 9 ng/mL) comparable to RA. Furthermore, OA patients (n = 152) with CRPM levels ≥ 9 ng/mL were more likely to develop contra-lateral knee OA assessed by X-ray over a two-year follow-up period with an odds ratio of 2.2 [1.0-4.7]. These data suggest that CRPM is a blood-based biochemical marker for early identification OA patients with an inflammatory phenotype.
Analysis of sequencing strategies and tools for taxonomic annotation: Defining standards for progressive metagenomics (2018)

Metagenomics research has recently thrived due to DNA sequencing technologies improvement, driving the emergence of new analysis tools and the growth of taxonomic databases. However, there is no all-purpose strategy that can guarantee the best result for a given project and there are several combinations of software, parameters and databases that can be tested. Therefore, we performed an impartial comparison, using statistical measures of classification for eight bioinformatic tools and four taxonomic databases, defining a benchmark framework to evaluate each tool in a standardized context. Using in silico simulated data for 16S rRNA amplicons and whole metagenome shotgun data, we compared the results from different software and database combinations to detect biases related to algorithms or database annotation. Using our benchmark framework, researchers can define cut-off values to evaluate the expected error rate and coverage for their results, regardless the score used by each software. A quick guide to select the best tool, all datasets and scripts to reproduce our results and benchmark any new method are available at https://github.com/Ales-ibt/Metagenomic-benchmark . Finally, we stress out the importance of gold standards, database curation and manual inspection of taxonomic profiling results, for a better and more accurate microbial diversity description.
Characterization and removal of silicon surface residue resulting from CHF3/C2F6 reactive ion etching (1994)

The surface properties of an underlying Si substrate after reactive ion etching of SiO2 in CHF3/C2F6 gas plasmas have been studied using x-ray photoelectron spectroscopy (XPS), secondary ion mass spectrometry, Rutherford backscattering spectroscopy, and high resolution transmission electron microscopy (HRTEM). A 50-nm-thick silicon layer that contains carbon and fluorine and a 4-nm-thick uniform residue layer composed entirely of carbon, fluorine, oxygen, and hydrogen on the silicon surface have been observed. The residue film has nine different kinds of chemical bonds. At the surface, O—F bond is found on C—F polymer that contains C—CFx (x≤3), C—F1, C—F2, and C—F3 bonds. Between the C—F polymer layer and the silicon substrate, C—C/H, Si—C, Si—O, and Si—F bonds exist. Neither point defect clusters nor distinct planar defects are found in cross-sectional HRTEM images of the silicon substrate. The changes of peak shapes for C, Si, O, and F in the residual film have been analyzed through an in situ resistive anneal under ultrahigh vacuum condition. C—F1, C—F2, and C—F3 bonds decompose and form C—CFx bonds above 200 °C. Above 400 °C, C—CFx bonds also decompose to C—C/H bonds. For removal of the silicon surface residue, reactive ion etched specimens have been exposed to O2, NF3, Cl2, and SF6 plasmas. By XPS analysis, NF3 treatment has been revealed to be the most effective. With 10 s exposure to NF3 plasma, the fluorocarbon residue film decomposes and the remaining fluorine is mostly bound to silicon. The fluorine completely disappears after wet cleaning.
Tubulin Photoaffinity Labeling with Biotin‐Tagged Derivatives of Potent Diketopiperazine Antimicrotubule Agents (2008)

NPI-2358 (1) is a potent antimicrotubule agent that was developed from a natural diketopiperazine, phenylahistin, which is currently in Phase I clinical trials as an anticancer drug. To understand the precise recognition mechanism of tubulin by this agent, we focused on its potent derivative, KPU-244 (2), which has been modified with a photoreactive benzophenone structure, and biotin-tagged KPU-244 derivatives (3 and 4), which were designed and synthesized for tubulin photoaffinity labeling. Introduction of the biotin structure at the p'-position of the benzophenone ring in 2 exhibited reduced, but significant biological activities with tubulin binding, tubulin depolymerization and cytotoxicity in comparison to the parent KPU-244. Therefore, tubulin photoaffinity labeling studies of biotin-derivatives 3 and 4 were performed by using Western blotting analysis after photoirradiation with 365 nm UV light. The results indicated that tubulin was covalently labeled by these biotin-tagged photoprobes. The labeling of compound 4 was competitively inhibited by the addition of diketopiperazine 1 or colchicine, and weakly inhibited by the addition of vinblastine. The results suggest that photoaffinity probe 4 specifically recognizes tubulin at the same binding site as anticancer drug candidate 1, and this leads to the disruption of microtubules. Probe 4 serves well as a useful chemical probe for potent antimicrotubule diketopiperazines, much like phenylahistin, and it also competes for the colchicine-binding site.
TRPM5 is a target in the modulation of taste perception and insulin secretion (133.4) (2014)

TRPM5 is a monovalent cation selective ion channels, activated by an increase of the intracellular Ca2+ concentration. Physiologically, TRPM5 is a key player in the transduction of taste signals and plays a role in the release of insulin from pancreatic ß‐cells. To date no pharmacological tools are available to evaluate the potential of TRPM5 as drug target for taste modulation or as insulin secretagogue. Here we show that the TRPM5 ion channel has potential as a target to stimulate insulin secretion in a mouse model We present a new class of compounds capable of potentiating TRPM5 signaling and analyze their working mechanism. We show activation of TRPM5 in a heterologous overexpression system and in a murine animal model. We show potentiation of sweet and bitter taste in a TRPM5 dependent way, using a two bottle preference test. Furthermore we observe increased glucose induced activity in the insulin secreting islets of Langerhans upon perfusion with our activator. These effects were completely abolished in TRPM5 knock‐out mice. In the high fat fed mouse, a model for type II diabetes, we showed that activating TRPM5 with our compound allows them to maintain a healthier glucose metabolism and delays the development of diabetes.
First Draft Genome Sequence of the Pathogenic Fungus <i>Lomentospora prolificans</i> (Formerly <i>Scedosporium prolificans</i> ) (2017)

Here we describe the sequencing and assembly of the pathogenic fungus <i>Lomentospora prolificans</i> using a combination of short, highly accurate Illumina reads and additional coverage in very long Oxford Nanopore reads. The resulting assembly is highly contiguous, containing a total of 37,627,092 bp with over 98% of the sequence in just 26 scaffolds. Annotation identified 8896 protein-coding genes. Pulsed-field gel analysis suggests that this organism contains at least 7 and possibly 11 chromosomes, the two longest of which have sizes corresponding closely to the sizes of the longest scaffolds, at 6.6 and 5.7 Mb.
MODY-like diabetes associated with an apparently balanced translocation: possible involvement of MPP7 gene and cell polarity in the pathogenesis of diabetes (2009)

Abstract Background Characterization of disease-associated balanced translocations has led to the discovery of genes responsible for many disorders, including syndromes that include various forms of diabetes mellitus. We studied a man with unexplained m aturity o nset d iabetes of the y oung (MODY)-like diabetes and an apparently balanced translocation [46,XY,t(7;10)(q22;p12)] and sought to identify a novel diabetes locus by characterizing the translocation breakpoints. Results Mutations in coding exons and splice sites of known MODY genes were first ruled out by PCR amplification and DNA sequencing. Fluorescent in situ hybridization (FISH) studies demonstrated that the translocation did not disrupt two known diabetes-related genes on 10p12. The translocation breakpoints were further mapped to high resolution using FISH and somatic cell hybrids and the junctions PCR-amplified and sequenced. The translocation did not disrupt any annotated transcription unit. However, the chromosome 10 breakpoint was 220 kilobases 5' to the Membrane Protein, Palmitoylated 7 ( MPP7 ) gene, which encodes a protein required for proper cell polarity. This biological function is shared by HNF4A , a known MODY gene. Databases show MPP7 is highly expressed in mouse pancreas and is expressed in human islets. The translocation did not appear to alter lymphoblastoid expression of MPP7 or other genes near the breakpoints. Conclusion The balanced translocation and MODY-like diabetes in the proband could be coincidental. Alternatively, the translocation may cause islet cell dysfunction by altering MPP7 expression in a subtle or tissue-specific fashion. The potential roles of MPP7 mutations in diabetes and perturbed islet cell polarity in insulin secretion warrant further study.
Recombinant human granulocyte ma_crophage colony_stimulating factor on leucopenia patients phase II clinical trials (1999)

AIM: To evaluate recombinant human granulocyte macrophage colony_stimulating factors (domestic rhGM_CSF) in prevention of neutropenia induced by cancer chemotherapy. METHODS: A multicenter, randomized, match and cross_over clinical trial of rhGM_CSF on leucopenia and neutropenia induced by combination chemotherapy on cancer patients was conducted. Sixty enrolled patients were randomized into AB and BA group. Each patients received two cycle treatment. In group AB, combination chemotherapy and rhGM_CSF were used in the first cycle and combination chemotherapy alone was used in the second cycle, while in group BA, combination chemotherapy alone was used in the first cycle and combination chemotherapy and rhGM_CSF were used in the second cycle. Four patients study were stopped for rhGM_CSF adverse reactions in 3 patients or disease progression in 1 patient, 56 patients were eligible for analysis of clinical efficacy. RESULTS: rhGM_CSF significantly increased the number of white blood cell (WBC) and absolute neutrophil count (ANC) at the nadir, decreased incidence of leucopenia and neutropenia and shorten the days with leucopenia and neutropenia induced by chemotherapy, rhGM_CSF also resulted in accelerating recovery of leucopenia and neutropenia on chemotherapy patients. The administration of rhGM_CSF ensures the cancer patients' chemotherapy in progress on schedule. The main adverse reactions with mild or moderate fever, injection side reaction, bone pain, myalgia, asthenia and skin rash were generally acceptable. CONCLUSION: The rhGM_CSF is a good adjuvant chemotherapy for cancer.
Per sub-block equalization and channel estimation for next generation handheld DVB (2009)

Orthogonal frequency division multiplexing (OFDM) systems may experience significant intercarrier interference (ICI) when used in doubly selective channels (time- and frequency-selective), particularly when large OFDM blocks are employed in order to achieve a high spectral efficiency. In this paper we recall a technique to mitigate ICI by splitting equalization at the receiver in two parts. A first pre-equalizer operates on sub-blocks of the received OFDM block with the aim of minimizing ICI, while a second, conventional equalizer adjusts phases on a per-subcarrier basis after OFDM demodulation. Moreover, we propose an estimation of channel parameters needed for equalization based on a superimposed pseudo-noise (PN) sequence method. Performance of the proposed receiver is evaluated for a possible extension of the new digital video broadcasting DVB-T2 standard to an handheld version (DVB-NGH). We show that bit error rate targets after channel decoding can be met at up to twice the speed of a conventional OFDM receiver, depending on channel dispersion.
Numerical simulation of carbon arc discharge for nanoparticle synthesis (2012)

Arc discharge with catalyst-filled carbon anode in helium background was used for the synthesis of carbon nanoparticles. In this paper, we present the results of numerical simulation of carbon arc discharges with arc current varying from 10 A to 100 A in a background gas pressure of 68 kPa. Anode sublimation rate and current voltage characteristics are compared with experiments. Distribution of temperature and species density, which is important for the estimation of the growth of nanoparticles, is obtained. The probable location of nanoparticle growth region is identified based on the temperature range for the formation of catalyst clusters.
Face recognition using distributed, mobile computing (2014)

This paper describes a distributed computing framework called Blue-Hoc, that uses mobile devices connected using a Bluetooth, wireless ad hoc network. For a network composed of different devices, we have developed a load balancing method to optimize performance of BlueHoc. The eigenfaces technique for face recognition is implemented and used to benchmark performance. With four devices and an 80 subject face database, we can achieve a speedup (including all overheads) of 1.37× without load balancing and with a 40 subject database a speedup of 1.08× with load balancing. Because of fixed communications and initialization costs, the speedup factor can grow as the number of subjects in the recognition system grows. Consequently, by aggregating the computing capabilities of local mobile devices, BlueHoc provides an effective solution for distributed mobile computing.
Controlled trial of cimetidine in upper gastrointestinal haemorrhage. (1979)

One hundred and one patients were studied in a double-blind controlled trial to assess the role of oral cimetidine in preventing the continuation or recurrence of acute upper gastrointestinal haemorrhage from various sources, chiefly peptic ulcer. The dose of cimetidine was 800 mg on entering the study followed by 400 mg six hourly. The source of bleeding was identified endoscopically in 96% of patients, peptic ulcer comprising 70%. Bleeding continued or recurred in 11 of 51 (21.5%) of patients on cimetidine and in 12 of 50 (24%) of patients on placebo. Analysis of the effect of cimetidine according to age or severity of bleeding showed no significant advantage for the drug.
Gasdynamic Characteristics of a Free-Vortex-Type Supersonic Laser Window. The Effect of Diffuser Configuration. (1996)

This paper describes an experimental study on the gasdynamic and aero-optical performance of a free-vortex aerodynamic laser window. The emphasis was placed on the effect of diffuser configuration. The pressure of a simulated laser cavity strongly depended on the position of diffuser blocks, especially on that of cavity side one. Although, the transversely averaged density and temporal fluctuation of the window jet gradually increased along the flow direction, the fluctuation level was 4kHz at worst.
Data from Nonequivalent Gene Expression and Copy Number Alterations in High-Grade Serous Ovarian Cancers with &lt;i&gt;BRCA1&lt;/i&gt; and &lt;i&gt;BRCA2&lt;/i&gt; Mutations (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; High-grade serous carcinoma (HGSC) accounts for the majority of epithelial ovarian cancer deaths. Genomic and functional data suggest that approximately half of unselected HGSC have disruption of the BRCA pathway and defects in homologous recombination repair (HRR). Pathway disruption is regarded as imparting a &lt;i&gt;BRCAness&lt;/i&gt; phenotype. We explored the molecular changes in HGSC arising in association with specific &lt;i&gt;BRCA1&lt;/i&gt;/&lt;i&gt;BRCA2&lt;/i&gt; somatic or germline mutations and in those with &lt;i&gt;BRCA1&lt;/i&gt; DNA promoter methylation.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We describe gene expression and copy number analysis of two large cohorts of HGSC in which both germline and somatic inactivation of HRR has been measured.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt;&lt;i&gt;BRCA1&lt;/i&gt; disruptions were associated with the C2 (immunoreactive) molecular subtype of HGSC, characterized by intense intratumoral T-cell infiltration. We derived and validated a predictor of &lt;i&gt;BRCA1&lt;/i&gt; mutation or methylation status, but could not distinguish &lt;i&gt;BRCA2&lt;/i&gt; from wild-type tumors. DNA copy number analysis showed that cases with &lt;i&gt;BRCA1&lt;/i&gt; mutation were significantly associated with amplification both at 8q24 (frequencies: &lt;i&gt;BRCA1&lt;/i&gt; tumors 50%, &lt;i&gt;BRCA2&lt;/i&gt; tumors 32%, and wild-type tumors 9%) and regions of the X-chromosome specifically dysregulated in basal-like breast cancer (BLBC; &lt;i&gt;BRCA1&lt;/i&gt; 62%, &lt;i&gt;BRCA2&lt;/i&gt; 34%, and wild-type 35%). Tumors associated with &lt;i&gt;BRCA1&lt;/i&gt;/&lt;i&gt;BRCA2&lt;/i&gt; mutations shared a negative association with amplification at 19p13 (&lt;i&gt;BRCA1&lt;/i&gt; 0%, &lt;i&gt;BRCA2&lt;/i&gt; 3%, and wild-type 20%) and 19q12 (&lt;i&gt;BRCA1&lt;/i&gt; 6%, &lt;i&gt;BRCA2&lt;/i&gt; 3%, and wild-type 29%).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; The molecular differences between tumors associated with &lt;i&gt;BRCA1&lt;/i&gt; compared with &lt;i&gt;BRCA2&lt;/i&gt; mutations are in accord with emerging clinical and pathologic data and support a growing appreciation of the relationship between HGSC and BLBC. &lt;i&gt;Clin Cancer Res; 19(13); 3474–84. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Quantitative Comparison of Conformational Ensembles (2012)

A number of measures have been used in the structural biology literature to compare the shapes or conformations of biological macromolecules. However, the issue of how to compare two ensembles of conformations has received far less attention. Herein, the problem of how to quantitatively compare two such ensembles is addressed in several different ways using concepts from probability and information theory. Ultimately, such metrics could be used in the evaluation of structure-prediction algorithms and the analysis of how conformational mobility is inhibited by bound ligands.
Deletion of D-helix in bovine pancreatic phospholipase A2. (1990)

D-Helix-deleted bovine pancreatic phospholipase A2 was designed using molecular mechanic calculations, and synthesized. Effects of the deletion on the enzymatic activity and on the structure were investigated. The enzymatic activity of the mutant protein was about 40% of that of the native one for a micellar substrate of 1,2-dioctanoyl-phosphatidylcholine. Although the Michaelis constant of the mutant enzyme was not changed, the catalytic constant was decreased. The dissociation constant of calcium ion was also changed. 1H NMR study revealed a slight conformation change around the active site of the mutant enzyme in addition to changes around the mutated region. The effect on the activity of the mutation seems to be due to the conformational changes around the active site.
A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness (2015)

Our study provides evidence that common DNA hypomethylation signature exists between cancer cells derived from different tissues, pointing to a common mechanism of cancer invasiveness in cancer cells from different origins that could serve as drug targets.
Compressing forwarding tables (2013)

With the rise of datacenter virtualization, the number of entries in forwarding tables is expected to scale from several thousands to several millions. Unfortunately, such forwarding table sizes can hardly be implemented today in on-chip memory. In this paper, we investigate the compressibility of forwarding tables. We first introduce a novel forwarding table architecture with separate encoding in each column. It is designed to keep supporting fast random accesses and fixed-width memory words. Then, we suggest an encoding whose memory requirement per row entry is guaranteed to be within a small additive constant of the optimum. Next, we analyze the common case of two-column forwarding tables, and show that such tables can be presented as bipartite graphs. We deduce graph-theoretical bounds on the encoding size. We also introduce an algorithm for optimal conditional encoding of the second column given an encoding of the first one. In addition, we explain how our architecture can handle table updates. Last, we evaluate our suggested encoding techniques on synthetic forwarding tables as well as on real-life tables.
Inhibition of <i>Mycobacterium tuberculosis</i> Dethiobiotin Synthase (<i>Mt</i>DTBS): Toward Next-Generation Antituberculosis Agents (2021)

<i>Mycobacterium tuberculosis</i> dethiobiotin synthase (<i>Mt</i>DTBS) is a crucial enzyme involved in the biosynthesis of biotin in the causative agent of tuberculosis, <i>M. tuberculosis</i>. Here, we report a binder of <i>Mt</i>DTBS, cyclopentylacetic acid <b>2</b> (<i>K</i><sub>D</sub> = 3.4 ± 0.4 mM), identified <i>via</i> <i>in silico</i> screening. X-ray crystallography showed that <b>2</b> binds in the 7,8-diaminopelargonic acid (DAPA) pocket of <i>Mt</i>DTBS. Appending an acidic group to the para-position of the aromatic ring of the scaffold revealed compounds <b>4c</b> and <b>4d</b> as more potent binders, with <i>K</i><sub>D</sub> = 19 ± 5 and 17 ± 1 μM, respectively. Further optimization identified tetrazole <b>7a</b> as a particularly potent binder (<i>K</i><sub>D</sub> = 57 ± 5 nM) and inhibitor (<i>K</i><sub>i</sub> = 5 ± 1 μM) of <i>Mt</i>DTBS. Our findings highlight the first reported inhibitors of <i>Mt</i>DTBS and serve as a platform for the further development of potent inhibitors and novel therapeutics for the treatment of tuberculosis.
Primary Cementless Hip Arthroplasty With a Titanium Plasma Sprayed Prosthesis (1996)

One hundred two patients underwent 105 primary uncemented total hip arthroplasties and werereviewed at a minimum of 5 years after operation (mean, 6.1 years). The components were titanium alloy with a titanium plasma spray coating. The acetabular revision rate was 11.4%. Acetabular cavitary lytic lesions were identified in 25.5% at 5 years. All acetabular revisions were performed for a combination of wear and osteolysis. One femoral revision was performed to facilitate an acetabular revision, but the femoral revision rate for aseptic loosening was 0%. In addition, no femoral components had subsided or were thought to be loose radiographically. Thigh pain was present in 4% at 5 years. Despite the 25.5% incidence of acetabular osteolysis, distal femoral lysis was not seen and only 5% showed focal osteolysis in the trochanteric region proximal to the circumferential porous coating of the femoral component. Component design features were thought to be critical to the excellent performance of the femoral component and to the poor performance of the acetabular component.