gebhart/patrepeval huggingface dataset:
HMM-based speech recognition system for the dysarthric speech evaluation of articulatory subsystem (2012)

Dysarthria is a neuromotor impairment of speech that affects one or more of the speech subsystems, but is often associated with irregular co-ordination of articulators and restricted movement of articulators among other problems. It is reflected in the acoustic characteristics of the phonemes as deviations from their healthy counterparts. To capture these deviations, in this work, isolated-style, phoneme recognition system is developed using monophone as the sub word unit. The performance of this phoneme recognition system for a dysarthric speaker can be directly related to the severity of the problem. To train the sub word unit models, speech data is collected from seven normal speakers. Time-aligned phonetic transcriptions are derived using forced Viterbi alignment procedure. Using this data, hidden Markov models for the required phonemes are trained. Nemours database contains time-aligned phonetic transcriptions for all the ten dysarthric speakers. Using these transcriptions, phonetic inventory is created for each of the dysarthric speakers separately. These phoneme segments are tested with the phoneme models trained using the normal speakers' data. The performance of this speech recognition system is analyzed after phoneme grouping, based on the place of articulation, for the assessment of the articulatory subsystem of the dysarthric speech. The analysis output correlates well with the Frenchey dysarthria assessment (FDA) scores provided with the database.
Clomiphene Prevents Cancellous Bone Loss from Tibia of Ovariectomized Rats (1997)

Estrogen inhibits postmenopausal bone loss and decreases fracture risk. Unfortunately, estrogen replacement therapy has many undesirable side effects, the majority of which are due to stimulation of reproductive tissues. Tissue specific estrogen agonists provide a promising new alternative to natural estrogens for hormone replacement. Clomiphene (CLO) is a substituted triphenylethylene antiestrogen based on its ability to antagonize estrogen-mediated uterine growth in rodents. CLO is used clinically for the treatment of disorders of ovulation in patients wishing to become pregnant. In order to determine whether CLO has tissue selective actions, we performed a dose-response study in adult (6-month-old) ovariectomized (OVX'd) rats. The rats received daily (gavage) doses of either 17 α-ethynyl estradiol (E) (0.1 mg/kg) or CLO (0.01–10 mg/kg) daily for 5 weeks. Long-term loss of ovarian function had no effect on serum cholesterol, greatly decreased uterine weight, cancellous bone area and trabecular number, and increased bone formation rate (BFR) and osteoblast and osteoclast perimeters. E treatment of OVX'd rats prevented uterine atrophy, greatly lowered cholesterol, and prevented many of the bone changes. CLO was a very weak estrogen agonist in supporting uterine weight, a partial agonist in reducing serum cholesterol, and an excellent agonist in maintaining normal bone mass and indices of bone turnover. We conclude from these studies that CLO exhibits pronounced tissue selective estrogen agonism in the rat. Specifically, CLO is effective in preventing cancellous bone loss in the OVX'd rats and has minimal uterotrophic activity.
Depletion of Regulatory T Cells in HIV Infection Is Associated with Immune Activation (2005)

Immune activation during chronic HIV infection is a strong clinical predictor of death and may mediate CD4(+) T cell depletion. Regulatory T cells (Tregs) are CD4(+)CD25(bright)CD62L(high) cells that actively down-regulate immune responses. We asked whether loss of Tregs during HIV infection mediates immune activation in a cross-sectional study of 81 HIV-positive Ugandan volunteers. We found that Treg number is strongly correlated with both CD4(+) and CD8(+) T cell activation. In multivariate modeling, this relationship between Treg depletion and CD4(+) T cell activation was stronger than any other clinical factor examined, including viral load and absolute CD4 count. Tregs appear to decline at different rates compared with other CD4(+) T cells, resulting in an increased regulator to helper ratio in many patients with advanced disease. We hypothesize that this skewing may contribute to T cell effector dysfunction. Our findings suggest Tregs are a major contributor to the immune activation observed during chronic HIV infection.
Detection of single nucleotide substitution by competitive allele-specific short oligonucleotide hybridization (CASSOH) with immunochromatographic strip (2003)

Recent advances in human genome research have revealed that genetic polymorphisms, such as single nucleotide polymorphisms (SNPs), are closely associated with susceptibility to various common diseases and adverse drug reactions. Also, numerous mutations responsible for a number of genetic diseases have been identified. Clinical application of genetic information to individual health care requires simple and rapid identification of nucleotide changes in clinical settings. We have devised a novel low-tech method for the detection of a single nucleotide substitution using competitive allele-specific short oligonucleotide hybridization with immunochromatographic strip. The gene of interest is PCR-amplified, hybridized to an allele-specific short oligonucleotide probe in the presence of a competitive oligonucleotide, and subjected to chromatography using a DNA test strip at room temperature. The genotype is unambiguously determined by the presence or the absence of visible purple lines on a strip. Feasibility of the method was demonstrated by the detection of a prevalent disease-causing mutations in glycogen storage disease type Ia (G6PC), medium-chain acyl-CoA dehydrogenase deficiency (ACADM), non-ketotic hyperglycinemia (GLDC), and clinically important polymorphisms in the CYP2C19 gene and the aldehyde dehydrogenase 2 gene (ALDH2). The procedure does not demand either technical expertise or expensive instruments and is readily performed in local clinical laboratories. The result is obtained within 10 min after PCR. This rapid and simple method of SNP detection may be used for point-of-care genetic diagnosis with potentially diverse clinical applications. Hum Mutat 22:166-172, 2003.
Direction finding for unstructured emitters in the presence of structured interferers (2002)

This paper addresses the problem of direction finding for unstructured emitters in environments that contain interference signals with exploitable properties. The CA-JML (copy aided joint maximum likelihood) algorithm, presented here, offers dramatic angle estimation improvement in environments that contain exploitable interference. The performance improvement is equivalent to the removal of the interferers from the environment. The complexity of the algorithm, however, is comparable to MUSIC. Even when structured interferers are not present, the CA-JML algorithm can reduce the angle error bias exhibited in MUSIC in challenging environments. The CA-JML algorithm also admits a simple relaxation technique as each emitter is localized, which reduces the probability of angle estimation error due to the presence of ambiguous peaks in the angle objective function.
Mutational Analysis of a Conserved Signal-Transducing Element: the HAMP Linker of theEscherichia coliNitrate Sensor NarX (2002)

The HAMP linker, a predicted structural element observed in sensor proteins from all domains of life, is proposed to transmit signals between extracellular sensory input domains and cytoplasmic output domains. HAMP (histidine kinase, adenylyl cyclase, methyl-accepting chemotaxis protein, and phosphatase) linkers are located just inside the cytoplasmic membrane and are projected to form two short amphipathic alpha-helices (AS-1 and AS-2) joined by an unstructured connector. The presumed helices are comprised of hydrophobic residues in heptad repeats, with only three positions exhibiting strong conservation. We generated missense mutations at these three positions and throughout the HAMP linker in the Escherichia coli nitrate sensor kinase NarX and screened the resulting mutants for defective responses to nitrate. Most missense mutations in this region resulted in a constitutive phenotype mimicking the ligand-bound state, and only one residue (a conserved Glu before AS-2) was essential for HAMP linker function. We also scanned the narX HAMP linker with an overlapping set of seven-residue deletions. Deletions in AS-1 and the connector resulted in constitutive phenotypes. Two deletions in AS-2 resulted in a novel reversed response phenotype in which the response to ligand was the opposite of that seen for the narX(+) strain. These observations are consistent with the proposed HAMP linker structure, show that the HAMP linker plays an active role in transmembrane signal transduction, and indicate that the two amphipathic alpha-helices have different roles in signal transduction.
Nerve growth factor binds to normal human keratinocytes through high and low affinity receptors and stimulates their growth by a novel autocrine loop. (1993)

Normal human keratinocytes synthesize and secrete biologically active nerve growth factor (NGF) in a growth regulated fashion (Di Marco, E., Marchisio, P. C., Bondanza, S., Franzi, A. T., Cancedda, R., and De Luca, M. (1991) J. Biol. Chem. 266, 21718-21722). Here we show that the same human keratinocytes bind NGF via low and high affinity receptors. In parallel with the course of NGF synthesis, the expression of low affinity NGF receptor (p75NGFr) decreases when a confluent, differentiated, and fully stratified epithelium is obtained. In skin sections, p75NGFr is present in basal keratinocytes and absent from suprabasal, terminally differentiated cells. The trkA protooncogene product (p140trkA), a component of the NGF receptor, is not expressed by keratinocytes. Instead, keratinocytes express a new member of the trk family (that we termed trkE), which generates 3.9-kilobase transcripts. Keratinocyte-derived NGF plays a key role in the autocrine epidermal cell proliferation. This has been proven by (i) direct effect of NGF on [3H]thymidine incorporation, (ii) inhibition of autocrine keratinocyte growth by monoclonal antibodies (alpha D11) inhibiting human NGF biological activity, and (iii) inhibition of autocrine keratinocyte proliferation by a trk-specific inhibitor, the natural alkaloid K252a. These data provide evidence that NGF, in addition to its effect as a survival and differentiation factor, is a potent regulator of cell proliferation, at least in human epithelial cells.
Conserved Structures and Diversity of Functions of RNA-Binding Proteins (1994)

In eukaryotic cells, a multitude of RNA-binding proteins play key roles in the posttranscriptional regulation of gene expression. Characterization of these proteins has led to the identification of several RNA-binding motifs, and recent experiments have begun to illustrate how several of them bind RNA. The significance of these interactions is reflected in the recent discoveries that several human and other vertebrate genetic disorders are caused by aberrant expression of RNA-binding proteins. The major RNA-binding motifs are described and examples of how they may function are given.
On the Affinity of Pig Pancreas Lipase for Tricaproin in Heterogeneous Solution (1945)

Summary The affinity of pig pancreas lipase towards tricaproin in heterogeneous mixtures has been determined at 30° C in the presence of sodium taurocholate and calcium chloride with constant shaking, (250 double oscillations per min.), the initial velocity of the reaction of hydrolysis in the lipid phase being calculated in relation to the initial surface of the lipid phase. In the investigated tricaproin emulsions with increasing amounts of tricaproin a normal and approximately uniform frequency distribution was found with regard to the logarithm of the diameters of the fatty particles. A conversion factor is computed from the relation between the total surface and the total volume of the particles and by means of this factor the total initial surface of the lipid phase in each enzymatic hydrolysis experiment can be calculated. – By the calculation of the affinity, FREUNDLICH'S adsorption isotherm has been applied to the adsorption of the enzyme in the surface layer of the lipid phase. The reciprocal value of k, where k is measure of the affinity of lipase towards undissolved tricaproin, is under the given experimental conditions equal to 130 cm 2 per 250 cc reaction mixture.
Lymph node localisation of biodegradable nanospheres surface modified with poloxamer and poloxamine block co‐polymers (1997)

Studies were performed to develop a sub-100 nm biodegradable colloidal system for the efficient delivery of drugs and diagnostic agents to the lymphatic system. Nanospheres of poly(lactide-co-glycolide) were prepared by interfacial polymer deposition. The nanospheres were coated with block co-polymers in order to modify their surface characteristics. Radiolabelling of the nanospheres for in vivo tracing was achieved by the incorporation of the lipophilic complex 111In-oxine during nanosphere preparation. In vitro stability of the radiolabelled nanospheres was determined in rat serum at 37 degrees C. The lymphatic distribution of the nanospheres was determined after subcutaneous administration to the rat. Lymphatic uptake of all coated systems was enhanced compared to the uncoated nanospheres, and a maximal uptake of 17% of the administered dose in the regional lymph nodes was achieved. These observations suggest that the nanospheres are suitable for diagnostic and therapeutic applications in clinical and experimental medicine.
How Polar Are Ionic Liquids? Determination of the Static Dielectric Constant of an Imidazolium-based Ionic Liquid by Microwave Dielectric Spectroscopy (2005)

In a pilot study of the dielectric constant of room-temperature ionic liquids, we use dielectric spectroscopy in the megahertz/gigahertz regime to determine the complex dielectric function of five 1-alkyl-3-methylimidazolium salts, from which the static dielectric constant epsilon is obtained by zero-frequency extrapolation. The results classify the salts as moderately polar solvents. The observed epsilon-values at 298.15 K fall between 15.2 and 8.8, and epsilon decreases with increasing chain length of the alkyl residue of the cation. The anion sequence is trifluoromethylsulfonate > tetrafluoroborate approximately tetrafluorophosphate. The results indicate markedly lower polarities than found by spectroscopy with polarity-sensitive solvatochromic dyes.
Isolation of a cDNA clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues. (1986)

We have isolated a hamster cDNA clone representing the coding sequences for the entire precursor of prion protein (PrP) 27-30. This clone encodes a protein of 254 residues and contains an in-frame ATG codon 42 bases upstream from the one previously reported. Analysis of the predicted amino acid sequence suggests that the PrP precursor protein contains an amino-terminal signal sequence, and a membrane-spanning domain in the carboxyl terminus. Cleavage of the signal peptide would produce a mature protein of 232 amino acids. Sequences homologous to the hamster PrP cDNA were detected in hamster, mouse, sheep, human, and rabbit genomes. A related 2.5-kilobase transcript was present in the brain of normal and scrapie-infected rodents. Two homologous transcripts, 2.5 and 1.1 kilobases, were detected in the lung and heart of normal animals. No PrP mRNA was detected in spleen stroma, a tissue known to contain high titers of scrapie. Antisera raised to the 27- to 30-kDa polypeptide detected the PrP in both normal and infected brains but failed to detect this protein in either normal or infected spleens. Homologous mRNA species were detected in human, sheep, and rabbit brain, even though the latter is resistant to scrapie infection. Our data suggest that PrP is not a necessary component of the infectious agent.
Infrared mesh filters fabricated by electron-beam lithography (1985)

Capacitive and inductive infrared mesh filters have been fabricated using electron-beam lithography combined with a lift-off procedure. A single level of PMMA was used to create positive tone patterns while a two-level metal-on-polymer process was used to create negative tone patterns. Resonant structures consisting of arrays of crossed metal dipoles and arrays of crossed slots in otherwise continuous metal films have been fabricated that have linewidths less than 0.25 μm, and which exhibit bandstop and bandpass transmissive properties, respectively.
Acetate production from hydrogen and [13C]carbon dioxide by the microflora of human feces (1988)

Fecal suspensions from humans were incubated with 13CO2 and H2. The suspensions were from subjects who harbored 10(8) and 10(10) methanogens per g (dry weight) of feces, respectively, and from a subject who did not harbor methanogens. Quantitative nuclear magnetic resonance spectroscopy showed that acetate labeled in both the methyl and carboxyl groups was formed by suspensions from the subject without methanogens and the subject with the lower concentrations of methanogens. The amounts of labeled acetate formed were in agreement with the amounts expected based on measurements of H2 utilization. No labeled acetate was formed by suspensions from the subject with the higher concentrations of methanogens, and essentially all of the H2 used was accounted for by CH4 production. Suspensions from the subject with lower concentrations of methanogens produced both methane and acetate from H2 and CO2. The results indicate that reduction of CO2 to acetate may be a major pathway for microbial production of acetate in the human colon except when very high concentrations of methanogens (ca. 10(10) per g [dry weight] of feces) are present. Double-labeled acetate was also formed from H2 and 13CO2 by fecal suspensions from nonmethanogenic and moderately methanogenic rats.
Neutralizing antibody responses to HIV: role in protective immunity and challenges for vaccine design (2004)

AIDS continues to be a major health problem throughout the world with a high degree of mortality and morbidity. Therefore, there is an urgent need for an effective anti-HIV vaccine. Although the correlates of protective immunity against infection by HIV remain unidentified, recent studies have demonstrated that both humoral and cellular responses are required for controlling viral replication. Vaccine efforts should therefore aim at developing broad and potent humoral as well as cellular responses. Anti-HIV T-cell responses can be generated both in animals and humans by several vaccine modalities. In contrast, broadly neutralizing antibody responses against HIV have not been elicited by any strategy tested in the clinic thus far. The presence of such responses has the potential to prevent the establishment of infection. If not, the presence of neutralizing antibodies may significantly reduce the number of cells that become infected, therefore reducing the inoculum, which may delay viral spread and allow for a better control of viral replication in the infected host. Finally, cytotoxic T-lymphocytes may facilitate the clearance of virally infected cells. One of the biggest challenges in HIV vaccine development is to design a HIV envelope immunogen that can induce protective neutralizing antibodies effective against the diverse HIV-1 strains that characterize the global pandemic. The focus of this article is to review the importance of antibodies and the strategies that are currently being used for inducing such antibodies.
Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. (1984)

A procedure is described for rapid concurrent synthesis on solid supports of hundreds of peptides, of sufficient purity to react in an enzyme-linked immunosorbent assay. Interaction of synthesized peptides with antibodies is then easily detected without removing them from the support. In this manner an immunogenic epitope of the immunologically important coat protein of foot-and-mouth disease virus (type O1) is located with a resolution of seven amino acids, corresponding to amino acids 146-152 of that protein. Then, a complete replacement set of peptides in which all 20 amino acids were substituted in turn at every position within the epitope was synthesized, and the particular amino acids conferring specificity for the reaction with antibody were determined. It was found that the leucine residues at positions 148 and 151 were essential for reaction with antisera raised against intact virus. A lesser contribution was derived from the glutamine and alanine residues at positions 149 and 152, respectively. Aside from the practical significance for locating and examining epitopes at high resolution, these findings may lead to better understanding of the basis of antigen-antibody interaction and antibody specificity.
Anti–prostate‐Specific membrane antigen‐based radioimmunotherapy for prostate cancer (2010)

Despite recent advances, advanced prostate cancer is suboptimally responsive to current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that targets prostate-specific membrane antigen (PSMA) shows promise and is an area of active investigation. J591 is a deimmunized IgG monoclonal antibody developed to target the extracellular domain of PSMA. Preclinical and early phase clinical studies using radiolabeled J591 have demonstrated efficacy in targeting tumor cells and decreasing levels of prostate-specific antigen. Radiolabeled J591 is well-tolerated, nonimmunogenic, and can be administered in multiple doses. The dose-limiting toxicity is reversible myelosuppression with little nonhematologic toxicity. Future studies will include approaches to optimize patient selection and incorporate novel strategies to improve the success of anti-PSMA radioimmunotherapy.
Study of some polyoxometallates of Keggin's type as potential antitumour agents (2004)

The antitumour action of three polyoxometallate compounds of Keggin's type: 12-molibdophosphoric acid (MoPA), 12-tungstophosphoric acid (WPA) and Mg salt of WPA (MgHWPA) was studied in vitro. For human cervix carcinoma (HeLa) cells survival, as well as for nonstimulated and stimulated peripheral blood mononuclear cells (PBMC), MTT test was applied and IC50 values of POMs were determinated. Index selectivity for WPA and MgHWPA are 1.9 and 1.8, calculated for nonstimulated, as well as 2.5 and 2.0, calculated for stimulated PBMS. Combination of studied POMs do not contribute to their lower IC50 values. Apoptosis detection implies mild cytotoxic effect of WPA and more cytostatical effect of MgHWPA. Combination of each of the studied POMs with caffeine decreases HeLa survival in dose dependent way. None of the studied POMs in the used concentrations (up to 100 mmol/L) damages blood cells and/or decreases their number.
The Chemotactic Behavior of Eosinophils in Patients With Chronic Rhinosinusitis (2003)

Nasal mucin and nasal tissue in chronic rhinosinusitis contains chemoattractants, which can induce active eosinophil migration. The eosinophil migration from patients with chronic rhinosinusitis was consistently higher compared with eosinophils from healthy control subjects. Because the eosinophils were obtained from the peripheral blood, this finding suggests activation of eosinophils in the systemic circulation in chronic rhinosinusitis.
How Women Legislate. By Sue Thomas. New York: Oxford University Press, 1994. 205p. $35.00 cloth, $14.95 paper. (1994)

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