gebhart/patrepeval huggingface dataset:
The effect of long-term vasodilatation on capillary growth and performance in rabbit heart and skeletal muscle (1984)

The long-term effect of adenosine and of a new xanthine derivative, 1-(5-oxohexyl)-3-methyl-7-propylxanthine (HWA 285) on capillary density was studied in rabbits. Doses of both agents were established in acute experiments such that they would produce a prolonged increase in coronary and skeletal muscle blood flows without significantly affecting blood pressure or cardiac output. These doses were then chronically administered (3 to 5 weeks) by continuous intravenous infusion from portable infusion pumps carried by the rabbits. Control animals were infused with saline. Long-term administration of adenosine and HWA 285 was well tolerated by the animals. In the acute experiments, adenosine (42 mumol.h-1 iv) reduced the heart rate and produced an increase in coronary blood flow (studied using 15 micrometers radioactive microspheres) and conductance of 38% and 65% respectively, with increases in skeletal muscle of 65% and 92%. Blood pressure, cardiac output and cardiac minute work were not affected. HWA 285 (57 mumol.h-1) slightly but significantly increased blood pressure, but did not affect heart rate, cardiac output or minute work. Coronary and skeletal muscle blood flow were increased by 41% and 72%, with conductance increases of 33% and 62% respectively. The number of all capillaries present was studied in the heart and skeletal muscle using histochemical staining for alkaline phosphatase. Myocardial capillary density (capillaries per mm2, means +/- SE) was 3092 +/- 97 in the adenosine infused group and 2870 +/- 153 in the HWA 285 infused group compared with 2426 +/- 93 in the controls, ie an increase of 27% (p less than 0.001) and 18% (p less than 0.02) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Structural Basis for the Active Site Inhibition Mechanism of Human Kidney-Type Glutaminase (KGA) (2014)

Glutaminase is a metabolic enzyme responsible for glutaminolysis, a process harnessed by cancer cells to feed their accelerated growth and proliferation. Among the glutaminase isoforms, human kidney-type glutaminase (KGA) is often upregulated in cancer and is thus touted as an attractive drug target. Here we report the active site inhibition mechanism of KGA through the crystal structure of the catalytic domain of KGA (cKGA) in complex with 6-diazo-5-oxo-L-norleucine (DON), a substrate analogue of glutamine. DON covalently binds with the active site Ser286 and interacts with residues such as Tyr249, Asn335, Glu381, Asn388, Tyr414, Tyr466 and Val484. The nucleophilic attack of Ser286 sidechain on DON releases the diazo group (N2) from the inhibitor and results in the formation of an enzyme-inhibitor complex. Mutational studies confirmed the key role of these residues in the activity of KGA. This study will be important in the development of KGA active site inhibitors for therapeutic interventions.
Fat tissue, aging, and cellular senescence (2010)

Fat tissue, frequently the largest organ in humans, is at the nexus of mechanisms involved in longevity and age-related metabolic dysfunction. Fat distribution and function change dramatically throughout life. Obesity is associated with accelerated onset of diseases common in old age, while fat ablation and certain mutations affecting fat increase life span. Fat cells turn over throughout the life span. Fat cell progenitors, preadipocytes, are abundant, closely related to macrophages, and dysdifferentiate in old age, switching into a pro-inflammatory, tissue-remodeling, senescent-like state. Other mesenchymal progenitors also can acquire a pro-inflammatory, adipocyte-like phenotype with aging. We propose a hypothetical model in which cellular stress and preadipocyte overutilization with aging induce cellular senescence, leading to impaired adipogenesis, failure to sequester lipotoxic fatty acids, inflammatory cytokine and chemokine generation, and innate and adaptive immune response activation. These pro-inflammatory processes may amplify each other and have systemic consequences. This model is consistent with recent concepts about cellular senescence as a stress-responsive, adaptive phenotype that develops through multiple stages, including major metabolic and secretory readjustments, which can spread from cell to cell and can occur at any point during life. Senescence could be an alternative cell fate that develops in response to injury or metabolic dysfunction and might occur in nondividing as well as dividing cells. Consistent with this, a senescent-like state can develop in preadipocytes and fat cells from young obese individuals. Senescent, pro-inflammatory cells in fat could have profound clinical consequences because of the large size of the fat organ and its central metabolic role.
Fabrication of an Organic p-n Homojunction Diode Using Electrochemically Cation- and Photochemically Anion-Doped Polymer (1995)

An organic p-n homojunction has been successfully constructed in a single strip of poly(3-methylthiophene) (PMT) film by electrochemical cation doping on one side and photosensitized anion doping on the other side. The rectifying effect observed with the Al/(cation:anion)-doped PMT/Au cell provides evidence for the formation of a p-n homojunction in the PMT film since both Al/cation-doped PMT/Al and Au/anion-doped PMT/Au cells exhibit ohmic behavior. The formation of p-n homojunction can be inferred from measured work functions of the electrochemically cation-doped PMT, photochemically anion-doped PMT, Al and Au films. The p-n homojunction cell yields a short-circuit photocurrent of 0.16 µ A· cm -2 , an open-circuit photovoltage of 0.23 V and a fill factor of 0.30. These voltaic and photovoltaic properties are found to be superior to those of the polymer diode based on a p-n junction made by pressure contact of the p-doped PMT film with the n-doped PMT film.
Tandem-free VoIP conferencing: a bridge to next-generation networks (2003)

This article surveys approaches to teleconferencing in voice over IP networks. The considerations for conferencing include perceived quality, scalability, control, and compatibility. Architectures used for conferencing range from centralized bridges to full mesh. Centralized conference bridges used with compressed speech degrade speech quality when multiple talkers are mixed and subjected to tandem coding operations. Full mesh and multicast solutions (mixing at the end-points) are inappropriate when the number of conferees is large. This article discusses a hybrid solution that incorporates tandem-free bridging (the bridge selects and forwards packets) and endpoint mixing.
On rectangular partitionings in two dimensions: algorithms, complexity and applications (1998)

Abstract. Partitioning a multi-dimensional data set into rectangular partitions subject to certain constraints is an important problem that arises in many database applications, including histogram-based selec-tivity estimation, load-balancing, and construction of index structures. While provably optimal and ecient algorithms exist for partitioning one-dimensional data, the multi-dimensional problem has received less attention, except for a few special cases. As a result, the heuristic parti-tioning techniques that are used in practice are not well understood, and come with no guarantees on the quality of the solution. In this paper, we present algorithmic and complexity-theoretic results for the fundamental problem of partitioning a two-dimensional array into rectangular tiles of arbitrary size in a way that minimizes the number of tiles required to sat-isfy a given constraint. Our main results are approximation algorithms for several partitioning problems that provably approximate the optimal solutions within small constant factors, and that run in linear or close to linear time. We also establish the NP-hardness of several partitioning problems, therefore it is unlikely that there are ecient, i.e., polynomial time, algorithms for solving these problems exactly. We also discuss a few applications in which partitioning problems arise. One of the applications is the problem of constructing multi-dimensional histograms. Our results, for example, give an ecient algorithm to con-struct the V-Optimal histograms which are known to be the most ac-curate histograms in several selectivity estimation problems. Our algo-rithms are the rst to provide guaranteed bounds on the quality of the solution. 1
House dust mite major allergens Der p 1 and Der p 5 activate human airway-derived epithelial cells by protease-dependent and protease-independent mechanisms (2006)

House dust mite allergens (HDM) cause bronchoconstriction in asthma patients and induce an inflammatory response in the lungs due to the release of cytokines, chemokines and additional mediators. The mechanism how HDM components achieve this is largely unknown. The objective of this study was to assess whether HDM components of Dermatophagoides pteronissinus with protease activity (Der p 1) and unknown enzymatic activity (Der p 2, Der p 5) induce biological responses in a human airway-derived epithelial cell line (A549), and if so, to elucidate the underlying mechanism(s) of action. A549 cells were incubated with HDM extract, Der p 1, recombinant Der p 2 and recombinant Der p 5. Cell desquamation was assessed by microscopy. The proinflammatory cytokines, IL-6 and IL-8, were measured by ELISA. Intracellular Ca2+ levels were assessed in A549 cells and in mouse fibroblasts expressing the human protease activated receptor (PAR)1, PAR2 or PAR4. HDM extract, Der p 1 and Der p 5 dose-dependently increased the production of IL-6 and IL-8. Added simultaneously, Der p 1 and Der p 5 further increased the production of IL-6 and IL-8. The action of Der p 1 was blocked by cysteine-protease inhibitors, while that of Der p 5 couldn't be blocked by either serine- or cysteine protease inhibitors. Der p 5 only induced cell shrinking, whereas HDM extract and Der p1 also induced cell desquamation. Der p 2 had no effect on A549 cells. Der p 1's protease activity causes desquamation and induced the release of IL6 and IL-8 by a mechanism independent of Ca2+ mobilisation and PAR activation. Der p 5 exerts a protease-independent activation of A549 that involves Ca2+ mobilisation and also leads to the production of these cytokines. Together, our data indicate that allergens present in HDM extracts can trigger protease-dependent and protease-independent signalling pathways in A549 cells.
A Case Report of Successful Treatment of Recalcitrant Childhood Localized Scleroderma with Infliximab and Leflunomide (2015)

Herein we report successful treatment of an adolescent Caucasian female with severe progressive localized scleroderma (mixed subtype, including generalized morphea and linear scleroderma of the trunk/limb) using infliximab and leflunomide. The patient demonstrated improvement after the first 9 months of therapy based on her clinical examination, objective measures, and patient and parent global assessments. Infliximab is a potential treatment option for pediatric localized scleroderma patients who have progression of disease or who are unable to tolerate the side effect profile of more standard systemic therapy. Larger longitudinal studies or case series are needed to confirm and further investigate infliximab's role in localized scleroderma.
Characterization of Fluorescein Isothiocyanate-Dextrans Used in Vesicle Permeability Studies (2002)

Fluorescein Isothiocyanate-dextrans of various weight average molecular masses (4,400-487,000) were analyzed in buffer solution for pH, osmolarity, fluorescence intensity as a function of the polymer concentration, average molecular masses, and radii of gyration. Labeling of polymers and conformation of the polymers were characterized by high-performance gel exclusion chromatography (HPLC-GEC) and small-angle X-ray scattering. The fluorescence measurements evidence the absence of fluorescence quenching of the FITC chromophores but the existence of an inner filter effect at high polymer concentration. The conformation of the polymers in buffer is very likely of random coil type, as shown by the relationship between the radii of gyration and the weight-average molecular masses of the dextrans (Mw). The medium used to analyze the FITC-dextrans by HPLC-GEC strongly influences their elution behavior. In buffer medium, they are sieved over the TSK G4000 PW column through a single population according to their Mw. whereas in pure water, they are separated into several species by an exclusion mechanism that depends on the number of labeled sites per dextran molecule. A Monte Carlo simulation was used to analyze the distribution of the fluorescent labels. HPLC-GEC in water could interestingly be applied to yield labeled polymers bearing a known number of functionalized groups.
Studies on sulphatases. 13. The hydrolysis of substituted phenyl sulphates by the arylsulphatase of Alcaligenes metalcaligenes (1956)

transitions appearing in the solidification-point curves of binary mixtures of branched-chain acids with normal fatty acids. As is characteristic of iso acids, the melting points of these fractions are about 1below the melting points of their corresponding normal acids (Weitkamp, 1945; Cason, 1948).
Transformation of follicular lymphoma to diffuse large B‐cell lymphoma proceeds by distinct oncogenic mechanisms (2006)

This study was undertaken to further elucidate the biological mechanisms underlying the frequent event of transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL). The gene expression profiles of 20 paired lymph node biopsies, derived from the same patient pre- and post-transformation, were analysed using the Lymphochip cDNA microarray. TP53 mutation analysis was performed and copy number alterations at the c-REL and CDNK2A examined. Immunohistochemistry was performed on an independent panel of paired transformation paraffin-embedded samples. Transformed follicular lymphoma was predominantly of the germinal centre B-like phenotype both at the mRNA and protein level. Despite this homogeneity, transformation proceeded by at least two pathways. One mechanism was characterised by high proliferation, as assessed by the co-ordinately expressed genes of the proliferation signature. This group was associated with the presence of recurrent oncogenic abnormalities. In the remaining cases, proliferation was not increased and transformation proceeded by alternative routes as yet undetermined. Genes involved in cellular proliferation prevailed amongst those that were significantly increased upon transformation and T cell and follicular dendritic-associated genes predominated amongst those that decreased. t-FL is a germinal centre B (GCB)-like malignancy that evolves by two pathways, one that is similar in proliferation rate to the antecedent FL and the other that has a higher proliferation rate and is characterised by the presence of recognised oncogenic abnormalities.
D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease (2003)

Parkinson disease (PD) is a neurodegenerative disorder characterized by a loss of the nigrostriatal dopaminergic neurons accompanied by a deficit in mitochondrial respiration. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes dopaminergic neurodegeneration and a mitochondrial deficit reminiscent of PD. Here we show that the infusion of the ketone body d-beta-hydroxybutyrate (DbetaHB) in mice confers partial protection against dopaminergic neurodegeneration and motor deficits induced by MPTP. These effects appear to be mediated by a complex II-dependent mechanism that leads to improved mitochondrial respiration and ATP production. Because of the safety record of ketone bodies in the treatment of epilepsy and their ability to penetrate the blood-brain barrier, DbetaHB may be a novel neuroprotective therapy for PD.
A Comparison of Selected Strategies for Adaptive Control of Wave Energy Converters (2011)

Wave-energy converters of the point-absorbing type (i.e., having small extension compared with the wavelength) are promising for achieving cost reductions and design improvements because of a high power-to-volume ratio and better possibilities for mass production of components and devices as compared with larger converter units. However, their frequency response tends to be narrow banded, which means that the performance in real seas (irregular waves) will be poor unless their motion is actively controlled. Only then the invested equipment can be fully exploited, bringing down the overall energy cost. In this work various control methods for point-absorbing devices are reviewed, and a representative selection of methods is investigated by numerical simulation in irregular waves, based on an idealized example of a heaving semisubmerged sphere. Methods include velocity-proportional control, approximate complex conjugated control, approximate optimal velocity tracking, phase control by latching and clutching, and model-predictive control, all assuming a wave pressure measurement as the only external input to the controller. The methods are applied for a single-degree-of-freedom heaving buoy. Suggestions are given on how to implement the controllers, including how to tune control parameters and handle amplitude constraints. Based on simulation results, comparisons are made on absorbed power, reactive power flow, peak-to-average power ratios, and implementation complexity. Identified strengths and weaknesses of each method are highlighted and explored. It is found that overall improvements in average absorbed power of about 100–330% are achieved for the investigated controllers as compared with a control strategy with velocity-proportional machinery force. One interesting finding is the low peak-to-average ratios resulting from clutching control for wave periods about 1.5 times the resonance period and above.
Challenges of sequencing human genomes (2010)

Massively parallel sequencing technologies continue to alter the study of human genetics. As the cost of sequencing declines, next-generation sequencing (NGS) instruments and datasets will become increasingly accessible to the wider research community. Investigators are understandably eager to harness the power of these new technologies. Sequencing human genomes on these platforms, however, presents numerous production and bioinformatics challenges. Production issues like sample contamination, library chimaeras and variable run quality have become increasingly problematic in the transition from technology development lab to production floor. Analysis of NGS data, too, remains challenging, particularly given the short-read lengths (35-250 bp) and sheer volume of data. The development of streamlined, highly automated pipelines for data analysis is critical for transition from technology adoption to accelerated research and publication. This review aims to describe the state of current NGS technologies, as well as the strategies that enable NGS users to characterize the full spectrum of DNA sequence variation in humans.
Platelet-Derived Growth Factor B, but Not Fibroblast Growth Factor 2, Plasmid DNA Improves Survival of Ischemic Myocutaneous Flaps (2004)

Matrix-enabled gene therapy may provide an effective nonsurgical approach for promoting flap survival and is well suited for surgical applications in which transient therapeutic transgene expression is desired.
Marginal Zone B-Cells, a Gatekeeper of Innate Immunity (2011)

To maintain the integrity of an organism constantly challenged by pathogens, the immune system is endowed with a variety of cell types. B lymphocytes were initially thought to only play a role in the adaptive branch of immunity. However, a number of converging observations revealed that two B-cell subsets, marginal zone (MZ) and B1 cells, exhibit unique developmental and functional characteristics, and can contribute to innate immune responses. In addition to their capacity to mount a local antibody response against type-2 T-cell-independent (TI-2) antigens, MZ B-cells can participate to T-cell-dependent (TD) immune responses through the capture and import of blood-borne antigens to follicular areas of the spleen. Here, we discuss the multiple roles of MZ B-cells in humans, non-human primates, and rodents. We also summarize studies - performed in transgenic mice expressing fully human antibodies on their B-cells and in macaques whose infection with Simian immunodeficiency virus (SIV) represents a suitable model for HIV-1 infection in humans - showing that infectious agents have developed strategies to subvert MZ B-cell functions. In these two experimental models, we observed that two microbial superantigens for B-cells (protein A from Staphylococcus aureus and protein L from Peptostreptococcus magnus) as well as inactivated AT-2 virions of HIV-1 and infectious SIV preferentially deplete innate-like B-cells - MZ B-cells and/or B1 B-cells - with different consequences on TI and TD antibody responses. These data revealed that viruses and bacteria have developed strategies to deplete innate-like B-cells during the acute phase of infection and to impair the antibody response. Unraveling the intimate mechanisms responsible for targeting MZ B-cells in humans will be important for understanding disease pathogenesis and for designing novel vaccine strategies.
Reductive Dissolution of Manganese(III/Iv) Oxides by Substituted Phenols (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReductive Dissolution of Manganese(III/Iv) Oxides by Substituted PhenolsAlan T. StoneCite this: Environ. Sci. Technol. 1987, 21, 10, 979–988Publication Date (Print):October 1, 1987Publication History Published online1 May 2002Published inissue 1 October 1987https://pubs.acs.org/doi/10.1021/es50001a011https://doi.org/10.1021/es50001a011research-articleACS PublicationsRequest reuse permissionsArticle Views2146Altmetric-Citations420LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Automated model-based bias field correction of MR images of the brain (1999)

We propose a model-based method for fully automated bias field correction of MR brain images. The MR signal is modeled as a realization of a random process with a parametric probability distribution that is corrupted by a smooth polynomial inhomogeneity or bias field. The method we propose applies an iterative expectation-maximization (EM) strategy that interleaves pixel classification with estimation of class distribution and bias field parameters, improving the likelihood of the model parameters at each iteration. The algorithm, which can handle multichannel data and slice-by-slice constant intensity offsets, is initialized with information from a digital brain atlas about the a priori expected location of tissue classes. This allows full automation of the method without need for user interaction, yielding more objective and reproducible results. We have validated the bias correction algorithm on simulated data and we illustrate its performance on various MR images with important field inhomogeneities. We also relate the proposed algorithm to other bias correction algorithms.