gebhart/patrepeval huggingface dataset:
Analysis of speech segments using variable spectral/temporal resolution (2002)

The authors present an approach for efficiently computing a compact temporal/spectral feature set for representing a segment of speech, with effective resolution depending on both frequency and time position within the segment. The goal is to mimic the resolution properties of the human auditory system, but using a computationally efficient FFT-based front end rather than a more complex auditory model. In particular they apply both frequency and time "warping" to FFT spectra to obtain good frequency resolution at low frequencies and good time resolution at high frequencies. Time resolution is also varied so that the center of the segment is better represented than the endpoints. The resolution can be varied by the selection of "warping" functions controlled using a small number of parameters. The method was experimentally verified for the classification of six stops extracted from the TIMIT continuous speech database. The best classification rate obtained was 81.2% for test data using 50 features computed with the method presented.
Employment pathways in a large cohort of adult cancer survivors (2005)

Cancer survival sometimes has long-term effects on employment and the ability to work. Employment outcomes can be improved with innovations in treatment and with clinical and supportive services aimed at better management of symptoms, rehabilitation, and accommodation of disabilities.
The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism (2020)

Urea transporters are a family of urea-selective channel proteins expressed in multiple tissues that play an important role in the urine-concentrating mechanism of the mammalian kidney. Previous studies have shown that knockout of urea transporter (UT)-B, UT-A1/A3, or all UTs leads to urea-selective diuresis, indicating that urea transporters have important roles in urine concentration. Here, we sought to determine the role of UT-A1 in the urine-concentrating mechanism in a newly developed UT-A1-knockout mouse model. Phenotypically, daily urine output in UT-A1-knockout mice was nearly 3-fold that of WT mice and 82% of all-UT-knockout mice, and the UT-A1-knockout mice had significantly lower urine osmolality than WT mice. After 24-h water restriction, acute urea loading, or high-protein (40%) intake, UT-A1-knockout mice were unable to increase urine-concentrating ability. Compared with all-UT-knockout mice, the UT-A1-knockout mice exhibited similarly elevated daily urine output and decreased urine osmolality, indicating impaired urea-selective urine concentration. Our experimental findings reveal that UT-A1 has a predominant role in urea-dependent urine-concentrating mechanisms, suggesting that UT-A1 represents a promising diuretic target.
A Galectin-3 Ligand Corrects the Impaired Function of Human CD4 and CD8 Tumor-Infiltrating Lymphocytes and Favors Tumor Rejection in Mice (2010)

Human CD8(+) tumor-infiltrating T lymphocytes (TIL), in contrast with CD8(+) blood cells, show impaired IFN-γ secretion on ex vivo restimulation. We have attributed the impaired IFN-γ secretion to a decreased mobility of T-cell receptors on trapping in a lattice of glycoproteins clustered by extracellular galectin-3. Indeed, we have previously shown that treatment with N-acetyllactosamine, a galectin ligand, restored this secretion. We strengthened this hypothesis here by showing that CD8(+) TIL treated with an anti-galectin-3 antibody had an increased IFN-γ secretion. Moreover, we found that GCS-100, a polysaccharide in clinical development, detached galectin-3 from TIL and boosted cytotoxicity and secretion of different cytokines. Importantly, we observed that not only CD8(+) TIL but also CD4(+) TIL treated with GCS-100 secreted more IFN-γ on ex vivo restimulation. In tumor-bearing mice vaccinated with a tumor antigen, injections of GCS-100 led to tumor rejection in half of the mice, whereas all control mice died. In nonvaccinated mice, GCS-100 had no effect by itself. These results suggest that a combination of galectin-3 ligands and therapeutic vaccination may induce more tumor regressions in cancer patients than vaccination alone.
A physiologic reduced oxygen protocol decreases the incidence of threshold retinopathy of prematurity. (2006)

Physiologic hypoxia is the normal fetal state. Exposure of newborn premature infants to hyperoxia down-regulates retinal vascular endothelial growth factor. This arrests the normal retinal vascular migration and causes vaso-obliteration, the first phase of ROP. The hypothesis is that maintaining SpO2 values between 83% and 93% in the immediate postgestation life, combined with strict control of oxygen fluctuations, prevents the early vaso-obliterative phase and subsequent development of severe ROP. Significant reduction of threshold disease after implementation of PROP in all three centers supports the hypothesis.
Infectivity Difference Between the Two Phenotypes of Autographa californica Nuclear Polyhedrosis Virus: Importance of the 64K Envelope Glycoprotein (1985)

SUMMARY Two phenotypes of Autographa californica nuclear polyhedrosis virus (AcNPV), occluded virus and budded virus (BV), are responsible for causing disease in Trichoplusia ni. Virus released from occlusion bodies by alkali (LOVAL) is more infectious in the gut than in the haemocoel whereas BV is more infectious in the haemocoel than in the gut. Reduction of infectivity of BV in the haemocoel by the monoclonal antibody AcV1 to a level comparable to LOVAL clearly implicates its target, a 64K phosphoglycoprotein abundant in the BV envelope but not detected in LOVAL, as being involved in BV×s greater infectivity in that location. Homologous antiserum reduces the infectivity of LOVAL in the gut to that of LOVAL in the haemocoel, suggesting an analogous envelope component may account for its greater infectivity in the gut.
Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta (2001)

Preclinical models have shown that transplantation of marrow mesenchymal cells has the potential to correct inherited disorders of bone, cartilage, and muscle. The report describes clinical responses of the first children to undergo allogeneic bone marrow transplantation (BMT) for severe osteogenesis imperfecta (OI), a genetic disorder characterized by defective type I collagen, osteopenia, bone fragility, severe bony deformities, and growth retardation. Five children with severe OI were enrolled in a study of BMT from human leukocyte antigen (HLA)–compatible sibling donors. Linear growth, bone mineralization, and fracture rate were taken as measures of treatment response. The 3 children with documented donor osteoblast engraftment had a median 7.5-cm increase in body length (range, 6.5-8.0 cm) 6 months after transplantation compared with 1.25 cm (range, 1.0-1.5 cm) for age-matched control patients. These patients gained 21.0 to 65.3 g total body bone mineral content by 3 months after treatment or 45% to 77% of their baseline values. With extended follow-up, the patients' growth rates either slowed or reached a plateau phase. Bone mineral content continued to increase at a rate similar to that for weight-matched healthy children, even as growth rates declined. These results suggest that BMT from HLA-compatible donors may benefit children with severe OI. Further studies are needed to determine the full potential of this strategy.
A Hidden Markov Model method, capable of predicting and discriminating β-barrel outer membrane proteins (2004)

Based on the above, we developed a strategy, that enabled us to screen the entire proteome of E. coli for outer membrane proteins. The results were satisfactory, thus the method presented here appears to be suitable for screening entire proteomes for the discovery of novel outer membrane proteins. A web interface available for non-commercial users is located at: http://bioinformatics.biol.uoa.gr/PRED-TMBB, and it is the only freely available HMM-based predictor for beta-barrel outer membrane protein topology.
New Reactions in the Crotonase Superfamily:  Structure of Methylmalonyl CoA Decarboxylase from Escherichia coli, (2000)

The molecular structure of methylmalonyl CoA decarboxylase (MMCD), a newly defined member of the crotonase superfamily encoded by the Escherichia coli genome, has been solved by X-ray crystallographic analyses to a resolution of 1.85 A for the unliganded form and to a resolution of 2.7 A for a complex with an inert thioether analogue of methylmalonyl CoA. Like two other structurally characterized members of the crotonase superfamily (crotonase and dienoyl CoA isomerase), MMCD is a hexamer (dimer of trimers) with each polypeptide chain composed of two structural motifs. The larger N-terminal domain contains the active site while the smaller C-terminal motif is alpha-helical and involved primarily in trimerization. Unlike the other members of the crotonase superfamily, however, the C-terminal motif is folded back onto the N-terminal domain such that each active site is wholly contained within a single subunit. The carboxylate group of the thioether analogue of methylmalonyl CoA is hydrogen bonded to the peptidic NH group of Gly 110 and the imidazole ring of His 66. From modeling studies, it appears that Tyr 140 is positioned within the active site to participate in the decarboxylation reaction by orienting the carboxylate group of methylmalonyl CoA so that it is orthogonal to the plane of the thioester carbonyl group. Surprisingly, while the active site of MMCD contains Glu 113, which is homologous to the general acid/base Glu 144 in the active site of crotonase, its carboxylate side chain is hydrogen bonded to Arg 86, suggesting that it is not directly involved in catalysis. The new constellation of putative functional groups observed in the active site of MMCD underscores the diversity of function in this superfamily.
Investigation of High-Reactivity Calcium Carbonate Sorbent for Enhanced SO2 Capture (1996)

Kinetics of ultrafast, high-temperature sulfation is investigated for two calcium carbonates from different sources, a commercial calcium hydroxide and a laboratory-made modified hydrated lime powder. Time-resolved kinetic data are obtained for a 0−600 ms time scale at a temperature of 1080 °C with in-situ particle size classification. A mean particle size of 3.9 μm is considered for sorbent comparison studies. It is observed that the high-surface-area Forsby carbonate exhibits extraordinarily high reactivity (50% in 500 ms) compared to other carbonate and hydrate powders. The difference in reactivity is most prominent in the short time scale of under 50 ms. Thorough investigations of the internal pore structure and surface area evolution in the initial 50 ms are conducted for both calcination and sulfation. The results elucidate the influence of internal pore structure in determining the initial reactivity and the final sorbent utilization.
Vom Labor zur Klinik: vollsynthetische Antitumor-Impfstoffe auf Kohlenhydratbasis (2000)

Dieser Aufsatz gibt einen Überblick über die Untersuchungen unserer Arbeitsgruppe zur Synthese von Oligosacchariden und Glycokonjugaten mit dem Ziel der Herstellung und Erprobung von Impfstoffen auf der Basis kohlenhydrathaltiger Tumorantigene. Unser Ausgangspunkt war die bekannte Tendenz transformierter Zellen, auf der Zelloberfläche vergleichsweise selektiv Kohlenhydratmotive in Form von Glycoproteinen oder Glycolipiden zu exprimieren. Angeregt wurden diese Untersuchungen dadurch, dass derartige Antitumor-Impfstoffe effektive Targets für Immunerkennung und -angriff sein könnten; es ist jedoch schwierig, ausreichende Substanzmengen aus natürlichen Quellen zu gewinnen. Nachdem die Totalsynthese tumorassoziierter Kohlenhydratantigene gelungen war, war im klinischen Umfeld zu klären, ob das menschliche Immunsystem auf solche vollsynthetischen Antigene zielgerichtet und sinnvoll antworten kann. Dafür wurden die Ressourcen von Chemie und Immunologie zu einem gemeinsamen Angriff zusammengeführt. Die Synthese von tumorassoziierten Kohlenhydratantigenen sowie die Immunkonjugation und die Ergebnisse der Impfung von Mäusen mit solchen Konstrukten werden beschrieben. Hierfür war die Konjugation an einen immunogenen Träger notwendig, wofür sich KLH-Konjugate als geeignet erwiesen. In präklinischen und klinischen Studien mit synthetischen Kohlenhydratkonjugaten als Impfstoffen ließ sich die Induktion einer IgM- und IgG-Antikörper-Reaktion zeigen. Eine andere Strategie bestand in der Verwendung von Glycopeptidclustern als Targets für den Immunangriff. Anfänglich richtete sich unsere Aufmerksamkeit auf mucinähnliche, O-glycosidisch gebundene Glycopeptide. Synthetische trimere Cluster von Glycoepitopen, die sich von den Tn-, TF- und Ley-Antigenen ableiteten, erwiesen sich nach geeigneter Biokonjugation als immunogen. Die Hoffnung ist, dass Patienten, die mit den synthetischen Kohlenhydrat-Impfstoffen in Kombination mit einem Adjuvans immunisiert werden, Antikörper gegen Tumorzellen produzieren und dass die Produktion solcher Antikörper der Ausbreitung des Tumors entgegenwirkt, wodurch die Überlebenschancen und die Prognose für die „Lebensqualität”︁ verbessert werden.
Fluorescein Provides a Resonance Gate for FRET from Conjugated Polymers to DNA Intercalated Dyes (2004)

Fluorescence spectra show that excitation of the cationic water-soluble conjugated polymer poly[(1,4-phenylene)-2,7-[9,9-bis(6'-N,N,N-trimethylammonium)-hexyl]fluorene diiodide] (1) results in inefficient fluorescence resonance energy transfer (FRET) to ethidium bromide (EB) intercalated within double-stranded DNA (dsDNA). When fluorescein (Fl) is attached to one terminus of the dsDNA, there is efficient FRET from 1 through Fl to EB. The cascading energy-transfer process was examined mechanistically via fluorescence decay kinetics and fluorescence anisotropy measurements. These experiments show that the proximity and conformational freedom of Fl provide a FRET gate to dyes intercalated within DNA which are optically amplified by the properties of the conjugated polymer. The overall process provides a substantial improvement over previous homogeneous conjugated polymer based DNA sensors, namely, in the form of improved selectivity.
Butane and propane oxidation by engineered cytochrome P450cam (2002)

The haem monooxygenase cytochrome P450cam has been engineered to oxidise the gaseous alkanes butane and propane to butan-2-ol and propan-2-ol, respectively, by the use of bulky amino acid substitutions to reduce the volume of the substrate pocket and thus improve the enzyme-substrate fit: the F87W/Y96F/T101L/V247L mutant oxidizes butane with a turnover rate of 750 min-1 and 95% yield based on NADH consumed while the wild-type enzyme has an activity of 0.4 min-1 with 4% yield.
Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. (2000)

We have previously shown that antibodies to CTLA-4, an inhibitory receptor on T cells, can be effective at inducing regression of transplantable murine tumors. In this study, we demonstrate that an effective immune response against primary prostate tumors in transgenic (TRAMP) mice can be elicited using a strategy that combines CTLA-4 blockade and an irradiated tumor cell vaccine. Treatment of TRAMP mice at 14 weeks of age resulted in a significant reduction in tumor incidence (15% versus control, 75%), as assessed 2 months after treatment. Histopathological analysis revealed that treated mice had a lower tumor grade with significant accumulation of inflammatory cells in interductal spaces when treated with anti-CTLA-4 and a granulocyte-macrophage colony-stimulating factor-expressing vaccine. Vaccination of nontransgenic mice with this regimen resulted in marked prostatitis accompanied by destruction of epithelium, indicating that the immune response was, at least in part, directed against normal prostate antigens. These findings demonstrate that this combinatorial treatment can elicit a potent antiprostate response and suggest potential of this approach for treatment of prostate cancer.
Surgical treatment of atrial fibrillation: a review (2004)

The optimal treatment of atrial fibrillation (AF) depends upon a proper understanding of the electrophysiological basis of its clinical manifestations. Whether AF is continuous (persistent) or intermittent (paroxysmal) depends on variable underlying electrophysiology and determines the choice of interventional treatment. The initiation of intermittent AF requires a "trigger", often, though not always, located near the orifices of pulmonary veins. In contrast, continuous AF does not need a "trigger" to be re-induced repetitively and does not depend on the pulmonary veins or other abnormal automatic foci for its induction or perpetuation. Simple pulmonary vein encircling confines the trigger to the pulmonary veins and, if expertly performed, will cure the majority of patients with intermittent AF. On the other hand, continuous AF requires a Maze procedure or variant thereof to eliminate atrial macro-reentry while allowing sinus rhythm to activate the entire atrial myocardium and preserve atrial transport function. This article reviews the development of the surgical Maze procedure and its implications for the treatment of AF by percutaneous intracardiac or epicardial, minimally invasive techniques. High-intensity focussed ultrasound, a new energy source generating frictional heat, appears promising in the creation of focussed transmural lesions, while preserving the integrity of coronary arterial walls.
MALDI-TOF MS Quantification of Coccidiostats in Poultry Feeds (2000)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a relatively new technique that is having a great impact on analyses. This study is the first to demonstrate the use of linear MALDI-TOF MS to identify and quantify coccidiostats in poultry feeds. 2,5-Dihydroxybenzoic acid (DHB) was found to be the best matrix. In MALDI-TOF MS, coccidiostats form predominantly [M + Na](+) ions, with additional small amounts of [M + K](+) and [M - H + 2Na](+) ions, and no obvious fragment ions. Salinomycin and narasin were unstable in the concentrated DHB matrix solution but were stable when dried on the MALDI-TOF MS probe. A simple fast Sep-pak C18 cartridge purification procedure was developed for the MALDI-TOF MS quantification of coccidiostats in poultry feeds. The MALDI-TOF MS limit of detection for lasalocid, monensin, salinomycin, and narasin standards was 251, 22, 24, and 24 fmol, respectively. The method detection limit for salinomycin and narasin in poultry feeds was 2.4 microgram/g.
Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid (2007)

Valproic acid (VPA) is a powerful teratogen causing birth defects in humans, including autism spectrum disorder (ASD), if exposure occurs during the first trimester of embryogenesis. Learning and memory alterations are common symptoms of ASD, but underlying molecular and synaptic alterations remain unknown. We therefore studied plasticity-related mechanisms in the neocortex of 2-week-old rats prenatally exposed to VPA and tested for changes in glutamate-mediated transmission and plasticity in the neocortex. We found a selective overexpression of NR2A and NR2B subunits of NMDA receptors, as well as the commonly linked kinase calcium/calmodulin-dependent protein kinase II. Synaptic plasticity experiments between pairs of pyramidal neurons revealed an augmented postsynaptic form of long-term potentiation. These results indicate that VPA significantly enhances NMDA receptor-mediated transmission and causes increased plasticity in the neocortex. Enhanced plasticity introduces a surprising perspective to the potential molecular and synaptic mechanisms involved in children prenatally exposed to VPA.
Chimeric antibody with human constant regions and mouse variable regions directed against carcinoma-associated antigen 17-1A. (1987)

We have cloned the genomic DNA fragments encoding the heavy and light chain variable regions of monoclonal antibody 17-1A, and we have inserted them into mammalian expression vectors containing genomic DNA segments encoding human gamma 3 and kappa constant regions. The transfer of these expression vectors containing mouse-human chimeric immunoglobulin genes into Sp2/0 mouse myeloma cells resulted in the production of functional IgG that retained the specific binding to the surface antigen 17-1A expressed on colorectal carcinoma cells.
Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs (2007)

Narcotic antitussives such as codeine reveal the antitussive effect primarily via the mu-opioid receptor in the central nervous system (CNS). The kappa-opioid receptor also seems to contribute partly to the production of the antitussive effect of the drugs. There is controversy as to whether delta-receptors are involved in promoting an antitussive effect. Peripheral opioid receptors seem to have certain limited roles. Although narcotic antitussives are the most potent antitussives at present, certain types of coughs, such as chronic cough, are particularly difficult to suppress even with codeine. In guinea pigs, coughs elicited by mechanical stimulation of the bifurcation of the trachea were not able to be suppressed by codeine. In gupigs with sub-acute bronchitis caused by SO2 gas exposure, coughing is difficult to inhibit with centrally acting antitussives such as codeine. Some studies suggest that neurokinins are involved in the development of codeine-resistant coughs. However, evidence supporting this claim is still insufficient. It is very important to characterize opiate-resistant coughs in experimental animals, and to determine which experimentally induced coughs correspond to which types of cough in humans. In this review, we describe the mechanisms of antitussive effects of narcotic antitussives, addressing codeine-sensitive and -resistant coughs, and including our own results.
Immobilized Iron(III) Metal Affinity Chromatography for the Separation of Phosphorylated Macromolecules: Ligands and Applications (1997)

Abstract This review highlights the advances in Fe(III)-Immobilized Metal Affinity Chromatography [Fe(III)-IMAC] for the separation and characterization of phosphorylated biomolecules. Fe(III)-IMAC has demonstrated a selective interaction with phosphate groups and other hard Lewis bases such as carboxylate and phenol functional groups. These properties make this technique useful for separating and studying macromolecules. Since phosphorylation is a central means of regulation in eukaryotes and prokaryotes, the development of Fe(III)-IMAC is important. Various iron chelating ligands and their properties are discussed. General features of Fe(III)-IMAC are examined and examples of useful separations are considered.
P-selectin mediates the interaction of circulating leukocytes with platelets and microvascular endothelium in response to oxidized lipoprotein in vivo. (1994)

These data emphasize the similarities between leukocyte adhesion in response to oxLDL and in other pathophysiologic conditions, identifying P-selectin as a crucial player in the interaction between leukocytes and microvascular endothelium as well as in the formation of circulating leukocyte/platelet aggregates.