gebhart/patrepeval huggingface dataset:
Histone Deacetylase Inhibitors (2003)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTHistone Deacetylase InhibitorsThomas A. Miller, David J. Witter, and Sandro BelvedereView Author Information Aton Pharma, Inc., 777 Old Sawmill River Road, Tarrytown, New York 10591 Cite this: J. Med. Chem. 2003, 46, 24, 5097–5116Publication Date (Web):October 28, 2003Publication History Received24 June 2003Published online28 October 2003Published inissue 1 November 2003https://doi.org/10.1021/jm0303094Copyright © 2003 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views5211Altmetric-Citations447LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (556 KB) Get e-AlertscloseSUBJECTS:Chemical structure,Inhibition,Inhibitors,Ketones,Peptides and proteins Get e-Alerts
Boosting Contextual Information for Deep Neural Network Based Voice Activity Detection (2015)

Voice activity detection (VAD) is an important topic in audio signal processing. Contextual information is important for improving the performance of VAD at low signal-to-noise ratios. Here we explore contextual information by machine learning methods at three levels. At the top level, we employ an ensemble learning framework, named multi-resolution stacking (MRS), which is a stack of ensemble classifiers. Each classifier in a building block inputs the concatenation of the predictions of its lower building blocks and the expansion of the raw acoustic feature by a given window (called a resolution). At the middle level, we describe a base classifier in MRS, named boosted deep neural network (bDNN). bDNN first generates multiple base predictions from different contexts of a single frame by only one DNN and then aggregates the base predictions for a better prediction of the frame, and it is different from computationally-expensive boosting methods that train ensembles of classifiers for multiple base predictions. At the bottom level, we employ the multi-resolution cochleagram feature, which incorporates the contextual information by concatenating the cochleagram features at multiple spectrotemporal resolutions. Experimental results show that the MRS-based VAD outperforms other VADs by a considerable margin. Moreover, when trained on a large amount of noise types and a wide range of signal-to-noise ratios, the MRS-based VAD demonstrates surprisingly good generalization performance on unseen test scenarios, approaching the performance with noise-dependent training.
Therapy of human non-small-cell lung carcinoma using antibody targeting of a modified superantigen (2001)

Superantigens activate T-cells by linking the T-cell receptor to MHC class II on antigen-presenting cells, and novel reactivity can be introduced by fusing the superantigen to a targeting molecule. Thus, an antibody-targeted superantigen, which activates T cells to destroy tumour cells, might be used as cancer therapy. A suitable target is the 5T4 oncofetal antigen, which is expressed on many carcinomas. We constructed a fusion protein from a Fab of a monoclonal antibody recognizing the 5T4 antigen, and an engineered superantigen. The recombinant product 5T4FabV13-SEA(D227A)bound the 5T4 antigen expressed on the human non-small-cell lung cancer cell line Calu-1 with a Kd of 1.2 nM while the substitution of Asp227 to Ala in the superantigen moiety reduced binding activity to MHC class II. 5T4FabV13-SEA(D227A)tumour reactivity was demonstrated in 7/7 NSCLC samples by immunohistochemistry, while normal tissue reactivity was low to moderate. 5T4FabV13-SEA(D227A)induced significant T-cell-dependent in vitro killing of sensitive 5T4 bearing Calu-1 cells, with maximum lysis at 10(-10)M, while the capacity to lyse MHC class II expressing cells was approximately 1000 times less effective. Immunotherapy of 5T4FabV13-SEA(D227A)against human NSCLC was investigated in SCID mice reconstituted with human peripheral blood mononuclear cells. Mice carrying intreperitoneally growing Calu-1 cells showed significant reduction in tumour mass and number after intravenous therapy with 5T4FabV13-SEA(D227A). Thus, 5T4FabV13-SEA(D227A)has highly attractive properties for therapy of human NSCLC.
PROSTATE-SPECIFIC ANTIGEN AFTER ANATOMIC RADICAL RETROPUBIC PROSTATECTOMY (1997)

In a series of 1623 men with a follow-up of 5 +/- 3 years (range 1-13) after anatomic RRP for clinically localized prostate cancer, 17% (276/1623) have shown recurrence. A detectable PSA was the only evidence of recurrence in 7.9%, whereas 2.5% have recurred locally and 5.4% have developed distant metastases. The overall actuarial progression-free rate for these men at 10 years was 68%. Actuarial rates at 10 years were 18% for development of an isolated PSA recurrence, 8% for local recurrence, and 9% for distant recurrence. The actuarial likelihood of a postoperative recurrence increased with increasing clinical stage, Gleason score, preoperative PSA level, and pathologic stage. Although not shown in our previous report, the actuarial rate of recurrence of tumors with a Gleason score of 7 was statistically different from that of tumors of higher Gleason score (8-10). As well, men with preoperative PSA levels of 10.1 to 20 ng/mL experienced recurrence at a significantly lower rate than did men with preoperative PSA levels greater than 20 ng/mL. By using a combination of Gleason score, pathologic stage, and surgical margin status, we demonstrated that the presence of a positive surgical margin did not dramatically affect recurrence in tumors of Gleason scores 2 to 6 with capsular penetration. Surgical margin status was important in high-grade tumors with capsular penetration. In fact, tumors with capsular penetration, Gleason score of at least 7, and a positive surgical margin behaved similarly to tumors with invasion of the seminal vesicles. Preservation of potency did not adversely influence cancer control. The Gleason score, presence or absence of seminal vesicle or lymph node involvement, and the timing of PSA recurrence are all important variables in predicting eventual local versus distant failure associated with an isolated rise in serum PSA. Overall actuarial cause-specific survival at 5 and 10 years was 99% and 93%. Although there was no difference in survival among men grouped by TNM stage or preoperative PSA, advancing histologic grade and pathologic stage did have an effect on actuarial cause-specific survival. Men undergoing RRP for clinically localized prostate cancer showed a 16% actuarial rate of development of metastatic disease at 10 years. This is considerably better than conservative therapy and justifies RRP as the treatment of choice for men with clinically localized disease who are otherwise healthy and have a greater than 10-year life expectancy.
In Search of Improved Fat Transfer Viability: A Quantitative Analysis of the Role of Centrifugation and Harvest Site (2003)

Fat grafting is an unpredictable procedure that continues to challenge the field of plastic surgery due to irregular resorption. Applications for this procedure are broad in both reconstructive and cosmetic plastic surgery. Fat grafts are carefully obtained and manipulated to obtain better graft takes and results, yet there is no universal agreement on what constitutes an ideal methodology. The present study examines adipocyte viability from four commonly used donor sites in five subjects. No statistical differences in adipocyte viability were demonstrated among abdominal fat, thigh fat, flank fat, or knee fat donor sites that were immediately removed and untreated (p < 0.225). In addition, no differences were observed in representative tissue samples that were removed and centrifuged (thigh, p = 0.508; knee, p = 0.302; flank, p = 0.088; abdomen, p = 0.533). On the basis of these quantitative data, neither harvest location nor centrifugation demonstrated any advantage in terms of lipocyte viability. Fat tissue transfers from these common sites may be considered equal, and centrifugation does not appear to enhance immediate fat tissue viability before implantation.
Sudden Cardiac Death With Apparently Normal Heart (2000)

In 50% of cases of SCD with structurally normal hearts, sudden death was the first manifestation of disease. An approach combining archived heart examinations with detailed review of the clinical history was effective in elucidating potential SCD mechanisms in 57% of cases.
Gait analysis of a human walker wearing robot feet as shoes (2002)

This work takes part in the project of development of an anthropomorphic biped robot, Bip. The technological construction has been completed and the robot has performed some slow static walks. The next stage is the implementation of fast and dynamic walking gaits, in other words anthropomorphic gaits. The robot feet have been designed with a three-axes force-moment sensor for reconstructing the center of pressure-zero moment point. To study and test these feet, the idea is simple: the experimental setup consists of a human walker wearing the Bip feet as shoes, a force-plate and a motion analysis system. The purpose is double. The first one is aimed at comparing the contact pressure forces reconstructed with the Bip sensor feet, with the data recorded by the force-plate. The second one consists in determining the influence of (relatively) heavy and rigid metallic shoes on the gait of a human walker. If these feet were proving to be a handicap for efficient and elegant human walking gaits, how could it be any different for the robot Bip? Fortunately the analysis shows that they do not really handicap the walker.
Palladium(II)-Catalyzed Tandem Cyclization/C–H Functionalization of Alkynes for the Synthesis of Functionalized Indoles (2012)

A palladium-catalyzed tandem cyclization/C-H functionalization of two alkynes was accomplished to construct a series of polycyclic functionalized indoles. A range of internal alkynes bearing synthetically useful functional groups were tolerated. A good regioselectivity was observed when alkyl-substituted alkynes were introduced into the reaction system, and a single product was obtained. Molecular oxygen was used as the terminal oxidant in the approach, rendering the reaction more sustainable.
Accumulation of intercellular adhesion molecule-1 in senile plaques in brain tissue of patients with Alzheimer's disease. (1994)

The still unsolved pathogenesis of Alzheimer's disease (AD) has been the subject of extensive speculation. Some years ago, a local acute phase reaction involving production of interleukin-1 (IL-1) and IL-6 was proposed as the triggering event in AD. Since it has been reported that these cytokines induce expression of intercellular adhesion molecule-1 (ICAM-1), we analyzed AD brain tissue cryosections for the presence of ICAM-1 by immunostaining and for ICAM-2 expression as a control. In senile plaques a marked diffuse or granular staining for the ICAM-1 domains 1, 4, and 5 was observed, whereas ICAM-2 expression was observed in microglial cells. Immunoprecipitation analysis demonstrated the presence of a 85 kd ICAM-1 molecule in AD frontal cortex. Our findings indicate that ICAM-1 accumulates in senile plaques as a complete 5-domain molecule at a relatively early stage of senile plaque formation. Our results are in support of a cytokine-mediated pathogenesis of senile plaque formation.
Protein Engineering Approaches in the Post-Genomic Era (2017)

Proteins are one of the most multifaceted macromolecules in living systems. Proteins have evolved to function under physiological conditions and, therefore, are not usually tolerant of harsh experimental and environmental conditions. The growing use of proteins in industrial processes as a greener alternative to chemical catalysts often demands constant innovation to improve their performance. Protein engineering aims to design new proteins or modify the sequence of a protein to create proteins with new or desirable functions. With the emergence of structural and functional genomics, protein engineering has been invigorated in the post-genomic era. The three-dimensional structures of proteins with known functions facilitate protein engineering approaches to design variants with desired properties. There are three major approaches of protein engineering research, namely, directed evolution, rational design, and de novo design. Rational design is an effective method of protein engineering when the threedimensional structure and mechanism of the protein is well known. In contrast, directed evolution does not require extensive information and a three-dimensional structure of the protein of interest. Instead, it involves random mutagenesis and selection to screen enzymes with desired properties. De novo design uses computational protein design algorithms to tailor synthetic proteins by using the three-dimensional structures of natural proteins and their folding rules. The present review highlights and summarizes recent protein engineering approaches, and their challenges and limitations in the post-genomic era. Keywords: De novo design, directed evolution, genomics, protein engineering, random mutagenesis, rational design.
The Evaluation and Management of Bradycardia (2000)

Bradycardia is a common finding during the clinical evaluation of both healthy patients and those who are ill. Bradycardia may be caused either by intrinsic dysfunction of or damage to the conduction system or by the response of normal tissues to extrinsic factors. In many cases, even profound bradycardia may be asymptomatic and have no immediate or long-term pathologic importance. In this article, we will briefly review the clinical presentation, pathophysiology, diagnostic evaluation, and treatment of patients with bradycardia.Clinical PresentationCardiac output is the left ventricular forward stroke volume multiplied by the heart rate. Patients with bradycardia may be . . .
Enhanced Pseudomonas aeruginosa Biofilm Development Mediated by Human Neutrophils (2005)

Cystic fibrosis (CF) lung disease features persistent neutrophil accumulation to the airways from the time of infancy. CF children are frequently exposed to Pseudomonas aeruginosa, and by adulthood, 80% of CF patients are chronically infected. The formation of biofilms is a particularly important phenotypic characteristic of P. aeruginosa that allows for bacterial survival despite aggressive antibiotic therapy and an exuberant immune response. Here, we show that the presence of neutrophils enhances initial P. aeruginosa biofilm development over a period of 72 h through the formation of polymers comprised of actin and DNA. F-actin was found to be a site of attachment for P. aeruginosa. These actin and DNA polymers are present in CF sputum, and disruption of the polymers dispersed the associated P. aeruginosa cells and reduced biofilm development. These findings demonstrate a potential maladaptation of the primary innate response. When the host fails to eradicate the infection, cellular components from necrotic neutrophils can serve as a biological matrix to facilitate P. aeruginosa biofilm formation.
Isotope dilution-liquid chromatography/electrospray ionization-tandem mass spectrometry for the determination of serum thyroxine as a potential reference method (1998)

A new candidate reference method is presented for the determination of thyroxine in serum. The method is based on isotope dilution-liquid chromatography/tandem mass spectrometry using electrospray for ionization. The internal standard used was 13C6-thyroxine, sample pretreatment consisted of protein precipitation and a two-step liquid/liquid extraction procedure, HPLC was performed on a C-18 column with an eluent containing methanol/water/formic acid (60:40:0.1, by volume), and finally thyroxine and its isotopically labeled analogue were measured in the selected reaction monitoring mode for the transitions m/z 777.7--> 731.7 and m/z 783.7--> 737.7, respectively. The detection limit for thyroxine was 6 pg, the within-run coefficient of variation was 1.1%. The samples were measured in six-fold: in duplicate on three independent days. The mean overall coefficient of variation of the method was 1.6%. The new method was evaluated by measuring nine control sera previously determined by an existing ID-GC/MS method. The differences between the results of the two methods ranged from-1.6% to +3.3%, with a mean of +0.2%.
Silicon-Germanium Strained Layer Materials in Microelectronics (1999)

Review: The use of Si1–xGex in microelectronics production is appealing not only because it is compatible with existing industrial technology used for the production of silicon-based microelectronics, but also because the induced strain caused by insertion of a layer of Si1–xGex(see Figure) can significantly improve their performance. The production and properties of these new materials are reviewed.
Induction of HIV‐specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV‐capturing nanospheres in macaques (2004)

We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and that intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody response in mice. In this study, to evaluate the protective effect of immunization, each three macaques was intranasally immunized with Con A-NS or inactivated simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) and then intravaginally challenged with a pathogenic virus, SHIV KU-2. After a series of six immunizations, vaginal anti-HIV-1 gp120 IgA and IgG antibodies were detected in all SHIV-NS-immunized macaques. After intravaginal challenge, one of the three macaques in each of the Con A-NS- and SHIV-NS-immunized groups was infected. Plasma viral RNA load of infected macaque in SHIV-NS-immunized macaques was substantially less than that in unimmunized control macaque and reached below the detectable level. However, it could not be determined whether intranasal immunization with SHIV-NS is effective in giving complete protection against intravaginal challenge. To explore the effect of the SHIV-NS vaccine, the remaining non-infected macaques were rechallenged intravenously with SHIV KU-2. After intravenous challenge, all macaques became infected. However, SHIV-NS-immunized macaques had lower viral RNA loads and higher CD4(+) T cell counts than unimmunized control macaques. Plasma anti-HIV-1 gp120 IgA and IgG antibodies were induced more rapidly in the SHIV-NS-immunized macaques than in the controls. The rapid antibody responses having neutralizing activity might contribute to the clearance of the challenge virus. Thus, SHIV-NS-immunized macaques exhibited partial protection to vaginal and systemic challenges with SHIV KU-2.
Glutathione-Dependent Dehydroascorbate Reduction:a Determinant of Dehydroascorbate Uptake by HumanPolymorphonuclear Leukocytes (1980)

Dehydroascorbate uptake and reduction are impaired in normal human polymorphonuclear leukocytes (PMN) preincubated with N-ethylmaleimide, and in glutathione reductase-deficient cells. We conclude that human PMN dehydroascorbate reduction is glutathione-dependent, and that dehydroascorbate reduction appears to be a necessary condition for cellular dehydroascorbate uptake.
FcγRIIB is differentially expressed during B cell maturation and in B‐cell lymphomas (2003)

FcgammaRIIB, a low affinity receptor for the Fc portion of immunoglobulin G (IgG), is thought to drive negative selection of B cells in germinal centers (GC) by inducing apoptosis upon interaction with immune complexes. Its expression was investigated by immunohistochemistry in 22 reactive lymphoid tissues and 112 B-cell lymphomas. Pre-GC mantle cells, marginal zone cells and their neoplastic counterparts expressed FcgammaRIIB. The B chronic lymphocytic leukaemia (B-CLL)/small lymphocytic lymphomas were also positive. Not detected in GC, FcgammaRIIB was expressed in 52% of follicular lymphomas and in 20% of diffuse large B cell lymphomas (DLBCL). In DLBCL, FcgammaRIIB expression was linked to transformation (P < 0.001). Re-analysis of a gene profile data set from the Lymphochip microarrays showed that FcgammaRIIB expression in the activated B-like DLBCL subgroup was higher than in the GC-like one (P < 0.04), and was associated with an adverse prognostic both in univariate (P < 0.003) and in multivariate analysis including the International Prognostic Indicator (IPI) (P < 0.01). Thus these results challenge the potential role of FcgammaRIIB during B-cell selection in GC, and suggest a prognostic value of FcgammaRIIB expression in DLBCL.
Increased Serum Vascular Endothelial Growth Factor Levels and Intrathyroidal Vascular Area in Patients with Graves’ Disease and Hashimoto’s Thyroiditis (1998)

Vascular endothelial growth factor (VEGF) is one of the angiogenic factors. We examined both thyroid volume and intrathyroidal vascular area by color flow Doppler ultrasonography in patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and subacute thyroiditis. The serum concentrations of thyroid hormones, TSH, TSH receptor antibodies, and VEGF were also examined. There was a significant increase in serum VEGF levels in patients with untreated GD and goitrous HT compared with those in healthy subjects. The serum VEGF levels in untreated patients with subacute thyroiditis were significantly higher than those in patients with untreated GD or HT. There was a significant correlation between serum VEGF levels and the ratio of intrathyroidal vascular area and thyroid area in untreated patients with GD who had a goiter larger than or equal to 40 cm3. There was also a significant correlation between serum VEGF and TSH levels in patients with HT who were hypothyroid and had a goiter. Serum VEGF levels decreased significantly in these patients after treatment; this was accompanied by a significant decrease in intrathyroidal vascular area and thyroid volume. Our study demonstrates that VEGF appears to play an important role in intrathyroidal angiogenesis in patients with GD and goitrous HT.
Effects of smoking on oral ecology. A review of the literature. (1990)

The smoking habit is associated with a variety of deleterious changes in the mouth. In this review, the toxicology of tobacco smoke and its effects on the saliva, oral commensal bacteria and fungi, and oral polymorphonuclear leukocytes, are described. Smoking increases salivary flow rate, but does not alter the composition of plaque or its rate of deposition. Smoking appears to enhance anaerobiosis in the oral cavity, and depress the activity of oral leukocytes. Additionally, tobacco smoke components may have a selective toxic effect on particular species of microbiota. Gingival fluid exudate is reduced in smokers, with the consequence that the carriage of leukocytes and immunoglobulins is likely to be diminished.