gebhart/patrepeval huggingface dataset:
Making large-scale support vector machine learning practical (1998)

Training a support vector machine (SVM) leads to a quadratic optimization problem with bound constraints and one linear equality constraint. Despite the fact that this type of problem is well understood, there are many issues to be considered in designing an SVM learner. In particular, for large learning tasks with many training examples, off-the-shelf optimization techniques for general quadratic programs quickly become intractable in their memory and time requirements. SVMlight is an implementation of an SVM learner which addresses the problem of large tasks. This chapter presents algorithmic and computational results developed for SVMlight V2.0, which make large-scale SVM training more practical. The results give guidelines for the application of SVMs to large domains.
COLD PCR HRM: a highly sensitive detection method for IDH1 mutations (2010)

The p.Arg132His mutation of isocitrate dehydrogenase 1 (IDH1(R132H) ) is a frequent alteration and a major prognostic marker in gliomas. However, direct sequencing of highly contaminated tumor samples may fail to detect this mutation. Our objective was to evaluated the sensitivity of a newly described amplification method, coamplification at lower temperature-PCR (COLD PCR), combined with high-resolution melting (HRM) for the detection of the IDH1(R132H) mutation. To this end, we used serial dilutions of mutant DNA with wild-type DNA. PCR-HRM assay detects IDH1(R132H) at an abundance of 25%, similar to the detection limit of direct Sanger sequencing. Introducing a run of COLD PCR allows the detection of 2% mutant DNA. Using two consecutive runs of COLD PCR, we detected 0.25% mutant DNA in a background of wild-type DNA, that mimics a tumor sample highly contaminated by normal DNA. We then analyzed 10 biopsies of tumor edges, considered free of tumor cells by histological analysis, and showed that immunohistochemistry of IDH1(R132H) was positive in three cases (30%), whereas double COLD PCR HRM was positive in the 10 cases studied (100%). In summary, COLD PCR HRM analysis is 100-fold more sensitive than Sanger sequencing, rendering this rapid and powerful strategy particularly useful for samples highly contaminated with normal tissue.
Thermal, Magnetic, and Luminescent Properties of Dendronized Ferrite Nanoparticles (2009)

The design, synthesis, and some properties of magnetic nanocrystals of ferrite functionalized by luminescent prodendritic ligands are described. Multipotent hybrids resulting from the coupling of an inorganic nanocore (metallic, alloy, or oxide nanoparticle) embedded in an organic shell currently elicit sustained research activity in various areas of materials science and notably in the development of numerous, potential applications, for example, as relevant building blocks for self-assembled arrays of nanoparticles with magneto-luminescence properties, as magnetically movable luminescent probes, or as platforms for biomedical applications. In this study, we have essentially focused on the covalent functionalization of γ-Fe2O3 magnetic nanoparticles, with an average diameter of 40 nm by engineered luminescent, liquid-crystalline oligo(phenylene vinylene)-based prodendritic ligands. The grafting rate of the various ligands on the oxide surface and the thermal stability and behavior of the hybrids have been studied in detail and are reported here. The dendronized nanoparticles exhibit room temperature ferrimagnetic behavior, as do the parent naked particle. Furthermore, the grafting of covalent organic chromophores confers to the ensemble luminescent properties that can be tuned by the structure of the luminophore. However, despite the liquid crystalline character of the luminescent ligands, none of the corresponding hybrids showed mesomorphic properties, a result attributed to the large size discrepancy between the nanocrystalline core and the ligand.
Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses (2001)

In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice. Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.
Structure‐Based Optimization of Protein Tyrosine Phosphatase‐1 B Inhibitors: Capturing Interactions with Arginine 24 (2008)

Further optimization efforts on the previously disclosed PTP-1B inhibitor 1 a led to the discovery of a new series of potent compounds, for example derivative 33, which targeted the second phosphotyrosine binding pocket near the catalytic site. In the new series, the N-sulfonylpiperidine group of 1 a was replaced with a smaller substituent, capable of forming a new hydrogen bond interaction with arginine 24. The series reported here maintains the binding mode of 1 a and has the added advantages of a lower molecular weight, smaller polar surface area, and fewer rotatable bonds.
Entire genome sequences of two new HCV subtypes, 6r and 6s, and characterization of unique HVR1 variation patterns within genotype 6 (2009)

Hepatitis C virus genotype 6 currently contains 21 recognized subtypes, 6a-6u, for which 6r and 6s lack complete genome sequences. In this study, we entirely sequenced variants QC245 and QC66 from Cambodian immigrants in Canada representing subtypes 6r and 6s, respectively. The two genomes shared 75.3% nucleotide similarities to each other and 72.0-82.9% to 21 reference sequences representing subtypes 6a-6q, 6t-6u and variants km41 and gz52557. QC66 and QC245 displayed genome lengths of 9473 and 9450 nt and each contained a single open reading frame of 9051 nt. In 10 protein encoding regions QC245 and QC66 shared common sizes with TV249/6t and 537796/6l isolates, respectively. Phylogenetic analyses demonstrated that QC245 was more closely related to subtype 6f, but both QC66 and QC245 were subtypically different from all other genotype 6 subtypes. Our full-length sequence data confirmed the status of subtype 6r and 6s within genotype 6. Analysis of partial sequences revealed seven 6t and two 6s isolates that were all isolated from Cambodian immigrants. Analysis of the hypervariable region 1 sequences of 81 genotype 6 variants revealed two unique patterns of variation. First, most variants showed an amino acid deletion at the 4th position and second, many contained a basic residue at the 7th position. Possible roles of these two variation patterns are further discussed.
Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT 1B/1D receptor agonists (2004)

Triptans are 5HT(1B/1D) receptor agonists commonly prescribed for migraine headache. Although originally designed to constrict dilated intracranial blood vessels, the mechanism and site of action by which triptans abort the migraine pain remain unknown. We showed recently that sensitization of peripheral and central trigeminovascular neurons plays an important role in the pathophysiology of migraine pain. Here we examined whether the drug sumatriptan can prevent and/or suppress peripheral and central sensitization by using single-unit recording in our animal model of intracranial pain. We found that sumatriptan effectively prevented the induction of sensitization (i.e., increased spontaneous firing; increased neuronal sensitivity to intracranial mechanical stimuli) in central trigeminovascular neurons (recorded in the dorsal horn), but not in peripheral trigeminovascular neurons (recorded in the trigeminal ganglion). After sensitization was established in both types of neuron, sumatriptan effectively normalized intracranial mechanical sensitivity of central neurons, but failed to reverse such hypersensitivity in peripheral neurons. In both the peripheral and central neurons, the drug failed to attenuate the increased spontaneous activity established during sensitization. These results suggest that neither peripheral nor central trigeminovascular neurons are directly inhibited by sumatriptan. Rather, triptan action appears to be exerted through presynaptic 5HT(1B/1D) receptors in the dorsal horn to block synaptic transmission between axon terminals of the peripheral trigeminovascular neurons and cell bodies of their central counterparts. We therefore suggest that the analgesic action of triptan can be attained specifically in the absence, but not in the presence, of central sensitization.
CROWDMOS: An approach for crowdsourcing mean opinion score studies (2011)

MOS (mean opinion score) subjective quality studies are used to evaluate many signal processing methods. Since laboratory quality studies are time consuming and expensive, researchers often run small studies with less statistical significance or use objective measures which only approximate human perception. We propose a cost-effective and convenient measure called crowdMOS, obtained by having internet users participate in a MOS-like listening study. Workers listen and rate sentences at their leisure, using their own hardware, in an environment of their choice. Since these individuals cannot be supervised, we propose methods for detecting and discarding inaccurate scores. To automate crowdMOS testing, we offer a set of freely distributable, open-source tools for Amazon Mechanical Turk, a platform designed to facilitate crowdsourcing. These tools implement the MOS testing methodology described in this pa per, providing researchers with a user-friendly means of performing subjective quality evaluations without the overhead associated with laboratory studies. Finally, we demonstrate the use of crowdMOS using data from the Blizzard text-to-speech competition, showing that it delivers accurate and repeatable results.
Engineering Guide to the Application of Microseismic Interpretations (2012)

abstract Microseismic monitoring (MSM) of hydraulic fracture treatments is routine in North America and has added significantly to our understanding of fracture growth. The interpretation of microseismic images is advancing steadily, extracting more information from event patterns, temporal evolution, and acoustic waveforms. The increasing amount of information from MSM provides significant opportunities to improve stimulation designs, completion strategies, and field development. However, the applications of microseismic interpretations are many times ill-defined, overlooked, or not applied properly. Numerous applications of microseismic measurements have been documented in technical publications, typically in the form of case histories focused on specific applications. The industry has lacked a compilation and comprehensive discussion of microseismic applications. This paper presents a practical guide for the engineering application of microseismic interpretations, documenting reliable application workflows while highlighting the consequences of misapplication of microseismic interpretations. The application of MSM starts with a reliable interpretation of fracture geometry and complexity, but the real value is in the application of the interpretation. This paper divides microseismic applications into three categories, real-time, completion strategies &amp; stimulation design, and field development. The MSM interpretation requirements for each category are documented and a comprehensive guide to properly applying these interpretations is presented. Applications issues such as determining the "effective" fracture surface area, the relationship between microseismic behavior and well performance, and fracture model calibration are addressed. There is a growing interest in advanced processing such as moment tensor inversion (MTI) and b-values to determine focal mechanisms, source parameters, and failure mechanisms associated with the microseismic events. However, the engineering application of these interpretations is not well understood. This paper includes a discussion of the applications of advanced processing results, emphasizing how the limitations and uncertainties of the processing affect the subsequent applications.
Immunostimulatory Sequences Regulate Interferon-inducible Genes but not Allergic Airway Responses (2006)

This study demonstrated that 1018 ISS is safe and pharmacologically active in the respiratory tract of asthmatics but, at this dose regimen, did not inhibit a fall in FEV(1) or other key features of the response to inhaled allergen challenge. This suggests that induction of IFN and IFN-inducible genes alone is not sufficient to inhibit allergen-induced responses in asthmatic subjects.
Effect of Vascular Lesions on Cognition in Alzheimer's Disease: A Community‐Based Study (2004)

In this comparison study of AD cases with and without vascular lesions, AD/V cases had less severe AD pathology than those with AD alone, indicating that cerebrovascular disease likely contributes to the severity of cognitive impairment in those with AD. Controlling for vascular risk factors in patients with AD may have a significant effect on severity of dementia.
Transformed PANSS Factors Intended to Reduce Pseudospecificity Among Symptom Domains and Enhance Understanding of Symptom Change in Antipsychotic-Treated Patients With Schizophrenia (2017)

Positive and Negative Syndrome Scale (PANSS) total score is the standard primary efficacy measure in acute treatment studies of schizophrenia. However, PANSS factors that have been derived from factor analytic approaches over the past several decades have uncertain clinical and regulatory status as they are, to varying degrees, intercorrelated. As a consequence of cross-factor correlations, the apparent improvement in key clinical domains (eg, negative symptoms, disorganized thinking/behavior) may largely be attributable to improvement in a related clinical domain, such as positive symptoms, a problem often referred to as pseudospecificity. Here, we analyzed correlations among PANSS items, at baseline and change post-baseline, in a pooled sample of 5 placebo-controlled clinical trials (N = 1710 patients), using clustering and factor analysis to identify an uncorrelated PANSS score matrix (UPSM) that minimized the degree of correlation between each resulting transformed PANSS factor. The transformed PANSS factors corresponded well with discrete symptom domains described by prior factor analyses, but between-factor change-scores correlations were markedly lower. We then used the UPSM to transform PANSS in data from 4657 unique schizophrenia patients included in 12 additional lurasidone clinical trials. The results confirmed that transformed PANSS factors retained a high degree of specificity, thus validating that low between-factor correlations are a reliable property of the USPM when transforming PANSS data from a variety of clinical trial data sets. These results provide a more robust understanding of the structure of symptom change in schizophrenia and suggest a means to evaluate the specificity of antipsychotic treatment effects.
The dispersed, repeated family of MAL loci in Saccharomyces spp (1984)

This report concludes our analysis of the various standard maltose-fermenting strains of Saccharomyces spp. We showed that, in addition to either the MAL2 or MAL4 functional locus present in the standard MAL2 and MAL4 strains, both strains contain two cryptic MALg genes mapping to the MAL1 and MAL3 locus positions. (Functional MAL loci appear to consist of two linked complementing gene functions, MALp and MALg. Cryptic MALg genes lack a linked functional MALp gene.) Using a probe containing a DNA fragment derived from the MAL6 locus, we detected three genomic HindIII fragments in both the MAL2 and MAL4 strains. Each of these HindIII fragments is shown to segregate in a Mendelian fashion and to be linked to one of the three MAL loci in each of the strains. We also detected additional fragments having significant sequence homology to the MAL6 probe but lacking in MAL-related functions.
A Screening Assay Cascade to Identify and Characterize Novel Selective Estrogen Receptor Downregulators (SERDs) (2015)

Here, we describe an approach to identify novel selective estrogen receptor downregulator (SERD) compounds with improved properties such as oral bioavailability and the potential of increased efficacy compared to currently marketed drug treatments. Previously, methodologies such as Western blotting and transient cell reporter assays have been used to identify and characterize SERD compounds, but such approaches can be limited due to low throughput and sensitivity, respectively. We have used an endogenous cell-imaging strategy that has both the throughput and sensitivity to support a large-scale hit-to-lead program to identify novel compounds. A screening cascade with a suite of assays has been developed to characterize compounds that modulate estrogen receptor α (ERα)-mediated signaling or downregulate ERα levels in cells. Initially, from a focused high-throughput screening, novel ERα binders were identified that could be modified chemically into ERα downregulators. Following this, cellular assays helped determine the mechanism of action of compounds to distinguish between on-target and off-target compounds and differentiate SERDs, selective estrogen receptor modulator (SERM) compounds, and agonist ERα ligands. Data are shown to exemplify the characterization of ERα-mediated signaling inhibitors using a selection of literature compounds and illustrate how this cascade has been used to drive the chemical design of novel SERD compounds.
Expression of human papillomavirus type 16 E6-E7 open reading frame varies quantitatively in biopsy tissue from different grades of cervical intraepithelial neoplasia (1995)

The proteins encoded by the human papillomavirus type 16 E6-E7 open reading frame are essential for transformation of the host cell. Two mRNA species, E6*I and E6*II, generated by alternative splicing of a polycistronic pre-mRNA, encode truncated E6 proteins and the E7 protein. Our investigation assessed whether or not the level of expression of E6*I and E6*II varies quantitatively in relation to the grade of cervical intraepithelial neoplasia (CIN). We used a quantitative reverse transcription PCR assay to quantify these transcripts in concurrently collected biopsy tissue and exfoliated cervical cells from 22 women with a normal cervix or various grades of CIN. We evaluated transcription profiles in relation to CIN grade and specimen type. The expression levels of E6*I and E6*II in exfoliated cervical cells did not vary significantly in relation to the grade of CIN. However, expression of E6*II was significantly diminished or absent in biopsy tissue obtained from CIN grade II and III lesions (P = 0.014). Our findings suggest that quantification of E6*I and E6*II expression in biopsy tissue may be more clinically relevant than analysis of exfoliated cells. The identification of distinct patterns of expression in association with low- and high-grade CIN suggests that quantification of E6*I and E6*II expression in biopsy tissue may have prognostic value as an indicator of CIN progression.
Soybean Seed Yield and Quality as a Response to Field Pennycress Residue (2012)

ABSTRACT Field pennycress ( Thlaspi arvense L.; hereafter pennycress) is an oilseed crop being investigated as an off‐season biofuel source that can potentially fit into the existing crop rotation cycle with soybean [ Glycine max (L.) Merr.]. The objective of this 2‐yr study was to evaluate the effect of pennycress residue on seed yield and quality components of soybean planted during five consecutive weeks, from mid‐May to mid‐June. In 2009 and 2010, the mean soybean dry weight seed yield after pennycress residue for all planting dates (4108 and 3490 kg ha −1 , respectively) was greater than yield from fallow control plots (3636 and 2992 kg ha −1 , respectively). However, in 2010, soybean planted after pennycress had slightly lower oil content (202 g kg −1 ) than that obtained from fallow control plots (207 g kg −1 ) ( P &lt; 0.01). Delayed planting until mid‐June resulted in lower population density, plant height, seed yield, and oil concentration. Before June, planting date had no significant influence on soybean seed yield and quality. Protein content in soybean seed was not affected by year, pennycress residue, or planting date. Variation in the experimental year temperature values led to significant changes in oil components. High temperatures decreased levels of linoleic, linolenic, and stearic acids but increased levels of palmitic and oleic acids. Overall, pennycress had no negative effect on the subsequent soybean crop.
Evaluation of mental retardation - Part 1: Etiologic classification of 4659 patients with mental retardation or multiple congenital abnormality and mental retardation (2007)

Patients with multiple congenital abnormalities and mental retardation are the most frequent patient group who are referred to a genetic clinic. Specific diagnosis for these patients will provide a better understanding of the possible reasons of pathogenesis, thereby providing more true information to families on recurrence risk, prognosis, possible treatment options and prenatal diagnosis. With the aim of finding out the etiology of the genetic diseases, 4659 patients who were classified into mental retardation or multiple congenital anomaly and mental retardation (MR or MCA/MR) group who were referred to Istanbul University, Departments of Medical Genetics of Cerrahpasa Medical Faculty and Istanbul Medical Faculty in between 1985 and 2005 were analyzed retrospectively and a two step study was generated: first step involved the etiologic classification of MR or MCA/MR group and the second evaluation of the factors that help in finding out the etiologies such as age at first observation, number and periods of observations and completion of laboratory tests. In the first part of the study, etiologic classification of the patients with MR or MCA/MR who were referred to genetic clinics of the two medical faculty of Istanbul University were mentioned. 2847 patients have had an etiological diagnosis (61.10%): from these patients, 1541 out of them had a chromosomal abnormality (33.07%), 555 were known single gene mutations (11.91%), 20 were recognized syndromes (00.42%), 567 were sequences (12.16%), 6 were associations (00.12%), 29 had spectrums (00.62%), 98 had structural abnormality of CNS (2.10%), and finally, 31 suffered from prematurity and its complications, toxic drugs, infections and hypoxic ischemic encephalopathy. This study will be the one of the biggest studies in Turkey and also around the world, evaluating the most frequent patient group referred to genetic clinics: MCA or MR.
Delayed Decision Switched Prediction Multi-Stage LSF Quantization (2005)

An apparatus and method of quantizing a sequence of input data vectors using delayed decision switched prediction and vector quantization. The method has the following steps of operation: (a) predicting a next vector element from said sequence of input data vectors to generate a set of prediction vectors; (b) subtracting the set of prediction vectors from the next vector element to generate a set of prediction error vectors; (c) multi-stage vector quantizing the set of prediction error vectors to generate a set of quantized prediction error vectors with each of the stages having at least one of the tables and local decision means to generate a final quantization error vector according to a predetermined distance measure; (d) selecting one predictor out of the set of predictors from the switched prediction step and selecting, for each of the stages, at least one entry from the set of tables of the vector quantization step according to the predetermined distance measure, generating a quantized data vector.