gebhart/patrepeval huggingface dataset:
Fibroblast Growth Factor 19 Increases Metabolic Rate and Reverses Dietary and Leptin-Deficient Diabetes (2004)

Hormonal control of metabolic rate can be important in regulating the imbalance between energy intake and expenditure that underlies the development of obesity. In mice fed a high-fat diet, human fibroblast growth factor 19 (FGF19) increased metabolic rate [1.53 +/- 0.06 liters O(2)/h.kg(0.75) (vehicle) vs. 1.93 +/- 0.05 liters O(2)/h.kg(0.75) (FGF19); P < 0.001] and decreased respiratory quotient [0.82 +/- 0.01 (vehicle) vs. 0.80 +/- 0.01 (FGF19); P < 0.05]. In contrast to the vehicle-treated mice that gained weight (0.14 +/- 0.05 g/mouse.d), FGF19-treated mice lost weight (-0.13 +/- 0.03 g/mouse.d; P < 0.001) without a significant change in food intake. Furthermore, in addition to a reduction in weight gain, treatment with FGF19 prevented or reversed the diabetes that develops in mice made obese by genetic ablation of brown adipose tissue or genetic absence of leptin. To explore the mechanisms underlying the FGF19-mediated increase in metabolic rate, we profiled the FGF19-induced gene expression changes in the liver and brown fat. In brown adipose tissue, chronic exposure to FGF19 led to a gene expression profile that is consistent with activation of this tissue. We also found that FGF19 acutely increased liver expression of the leptin receptor (1.8-fold; P < 0.05) and decreased the expression of acetyl coenzyme A carboxylase 2 (0.6-fold; P < 0.05). The gene expression changes were consistent with the experimentally determined increase in fat oxidation and decrease in liver triglycerides. Thus, FGF19 is able to increase metabolic rate concurrently with an increase in fatty acid oxidation.
Distinct tyrosine phosphorylation sites in JAK3 kinase domain positively and negatively regulate its enzymatic activity (1997)

Cytokines are critically important for the growth and development of a variety of cells. Janus kinases (JAKs) associate with cytokine receptors and are essential for transmitting downstream cytokine signals. However, the regulation of the enzymatic activity of the JAKs is not well understood. Here, we investigated the role of tyrosine phosphorylation of JAK3 in regulating its kinase activity by analyzing mutations of tyrosine residues within the putative activation loop of the kinase domain. Specifically, tyrosine residues 980 and 981 of JAK3 were mutated to phenylalanine individually or doubly. We found that JAK3 is autophosphorylated on multiple sites including Y980 and Y981. Compared with the activity of wild-type (WT) JAK3, mutant Y980F demonstrated markedly decreased kinase activity, and optimal phosphorylation of JAK3 on other sites was dependent on Y980 phosphorylation. The mutant Y980F also exhibited reduced phosphorylation of its substrates, gammac and STAT5A. In contrast, mutant Y981F had greatly increased kinase activity, whereas the double mutant, YY980/981FF, had intermediate activity. These results indicate that Y980 positively regulates JAK3 kinase activity whereas Y981 negatively regulates JAK3 kinase activity. These observations in JAK3 are similar to the findings in the kinase that is closely related to the JAK family, ZAP-70; mutations of tyrosine residues within the putative activation loop of ZAP-70 also have opposing actions. Thus, it will be important to determine whether this feature of regulation is unique to JAK3 or if it is also a feature of other JAKs. Given the importance of JAKs and particularly JAK3, it will be critical to fully dissect the positive and negative regulatory function of these and other tyrosine residues in the control of kinase activity and hence cytokine signaling.
Hemodynamic Aspects of Alzheimer's Disease (2002)

Neuroradiological functional imaging techniques demonstrate the patterns of hypoperfusion and hypometabolism that are thought to be useful in the differential diagnosis of Alzheimer's disease (AD) from other dementing disorders. Besides the distribution patterns of perfusion or energy metabolism, vascular transit time (VTT), vascular reactivity (VR), and oxygen extraction fraction (OEF), which can be measured with positron emission tomography (PET), provide hemodynamic aspects of brain pathophysiology. In order to evaluate the hemodynamic features of AD, PET studies were carried out in 20 patients with probable AD and 20 patients with vascular dementia (VaD). The PET findings were not included in their diagnostic process of AD. Using oxygen-15-labeled compounds, cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), OEF, cerebral blood volume, and VTT were measured quantitatively during resting state. To evaluate VR, CBF was also measured during CO(2) inhalation. There was a significant increase in OEF in and around the parietotemporal cortices, but both VTT and VR were well preserved in patients with AD. By contrast, VR was markedly depressed and VTT was mildly prolonged in patients with VaD. Thus, from the hemodynamic point of view, the preservation of vascular reserve may be a distinct difference between AD and VaD. Furthermore, this indicates a hemodynamic integrity of the vasculature in the level of arterioles in AD.
Correlation between oxidation potential and open-circuit voltage of composite solar cells based on blends of polythiophenes/ fullerene derivative (2004)

The photovoltaic parameters of donor/acceptor blend organic solar cells are highly influenced by several parameters, such as the strength of the acceptor species, the morphology of the film due to the solvent, and the mobility of the free charge carriers. In this work, the open-circuit voltage (Voc) of solar cells based on series of conjugated polythiophene polymers were measured and compared. In every cell, the donor polymer was blended with an electron acceptor fullerene molecule. The devices were constructed in a sandwich structure with indium tin oxide (ITO)/metallic polymer (PEDOT:PSS) acting as an anode and Al or LiF/Al acting as a cathode. Comparing the Voc of all the cells shows that this important photovoltaic parameter is systematically varying with the polymer. The variation of photovoltage is attributed to the variation of the oxidation potential of the donor conjugated polymers after due consideration of the different injection conditions in the varying polymers.
The potential utility of urinary biomarkers for risk prediction in combat casualties: a prospective observational cohort study (2015)

Urinary biomarker levels at the time of admission are associated with death or need for renal replacement therapy. Larger multicenter studies will be required to determine how urinary biomarkers can best be used in future prediction models.
Three-Dimensional Free-Flight Analysis of the Rapid Turning of a Dragonfly Using Fluid-Structure Interaction Analysis (2013)

Recent studies of the flapping flight of insects have succeeded in solving the unsteady aerodynamics of hovering and contributed to realizing bio-inspired micro aerial vehicles (MAVs). However, the effect of wing deformation on the aerodynamics has not been investigated because of a lack of appropriate analysis methods. As an initial step to creating a “total” simulator for flapping flight, we developed a free-flight simulator by combining fluid-structure interaction finite element analysis based on the arbitrary Lagrangian-Eulerian method, which can quantitatively treat the strong interaction between the wing deformation and its surrounding airflow, and a rigid body dynamics analytical solver. With biologically-inspired flapping motion, which mimicked the changes in the stroke motion of the wing, the numerical model of the dragonfly performed rapid turning over 1200°/s of yaw angular velocity. Although the flapping motion for the left wing on the trigger flapping and the right wing on the resumed flapping (or its inversed combination) are identical, a considerable difference in the deformation of the wing during this identical flapping between the former and latter halves of the turn was observed. Thus, while these actuations were identical, the directions of the aerodynamic forces were largely controlled by passive deformations of the wings. These results meant that the effect of wing deformation on its aerodynamics should be taken into account and thus fluid-structure interaction analysis is required to effectively design the actuation of the wing on an artificial MAV.
Pharmaceutical quality of seven generic Levodopa/Benserazide products compared with original Madopar® / Prolopa® (2013)

Deviations for the active ingredients may go unnoticed by a new user of the generic product, but may entail clinical consequences when switching from original to generic during a long-term therapy. Degradation products may pose a safety concern. Our results should prompt caution when prescribing a generic of Madopar®/Prolopa®, and also invite to further investigations in view of a more comprehensive approach, both pharmaceutical and clinical.
EIT images of ventilation: what contributes to the resistivity changes? (2005)

One promising application of electrical impedance tomography (EIT) is the monitoring of pulmonary ventilation and edema. Using three-dimensional (3D) finite difference human models as virtual phantoms, the factors that contribute to the observed lung resistivity changes in the EIT images were investigated. The results showed that the factors included not only tissue resistivity or vessel volume changes, but also chest expansion and tissue/organ movement. The chest expansion introduced artifacts in the center of the EIT images, ranging from -2% to 31% of the image magnitude. With the increase of simulated chest expansion, the percentage contribution of chest expansion relative to lung resistivity change in the EIT image remained relatively constant. The averaged resistivity changes in the lung regions caused by chest expansion ranged from 0.65% to 18.31%. Tissue/organ movement resulted in an increased resistivity in the lung region and in the center anterior region of EIT images. The increased resistivity with inspiration observed in the heart region was caused mainly by a drop in the heart position, which reduced the heart area at the electrode level and was replaced by the lung tissue with higher resistivity. This study indicates that for the analysis of EIT, data errors caused by chest expansion and tissue/organ movement need to be considered.
Mathematics and the unexpected (1989)

Not the least unexpected thing about Mathematics and the Unexpected is that a real mathematician should write not just a literate work, but a literary one.-Ian Stewart, New Scientist In this brief, elegant treatise, assessable to anyone who likes to think, Ivar Ekelund explains some philosophical implications of recent mathematics. He examines randomness, the geometry involved in making predictions, and why general trends are easy to project (it will snow in January) but particulars are practically impossible (it will snow from 2 p.m. to 5 p.m. on the 21st).-Village Voice
Nonstationary environment compensation based on sequential estimation (1998)

Sequential approaches are proposed to compensate for the effects of the nonstationary environment for robust speech recognition. Unlike the batch approaches, the proposed methods derive a different parameter estimate for each time using the sequential expectation maximization (EM) algorithm. Moreover, we also propose the forward-backward estimation scheme as an improvement of the sequential parameter estimation.
Automatic approaches towards vehicle make and model recognition (2008)

A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy at Loughborough University.
Superquenching and Its Applications in J-Aggregated Cyanine Polymers (2001)

We report the observation of a “superquenching” for water-soluble poly-l-lysine derivatives containing an appended cationic cyanine dye on each repeat unit. The formally nonconjugated cyanine dye chromophores strongly associate in a “J” aggregate structure characterized by a sharp red-shifted absorption (compared to the monomer) and a similarly sharp red-shifted fluorescence. Superquenching is manifested by very large “Stern−Volmer” constants for fluorescence quenching by oppositely charged electron acceptors or energy transfer dyes; substantial quenching is observed at levels of quencher corresponding to one to four molecules per polymer chain. The quenching observed for these polymers is equivalent or greater to that previously observed for conjugated polyelectrolytes. We have been able to exploit the superquenching of the “J” aggregate polymer fluorescence in a competitive bioassay.
Equilibrium Polymerization of Sulfur (1959)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEquilibrium Polymerization of SulfurArthur V. Tobolsky and Adi EisenbergCite this: J. Am. Chem. Soc. 1959, 81, 4, 780–782Publication Date (Print):March 1, 1959Publication History Published online1 May 2002Published inissue 1 March 1959https://pubs.acs.org/doi/10.1021/ja01513a004https://doi.org/10.1021/ja01513a004research-articleACS PublicationsRequest reuse permissionsArticle Views908Altmetric-Citations248LEARN 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
Similarity and functional analyses of expressed parasitism genes in Heterodera schachtii and Heterodera glycines (2008)

The secreted proteins encoded by expressed within the esophageal glands cells of cyst nematodes play important roles in plant parasitism. Homologous transcripts and encoded proteins of the Heterodera glycines pioneer parasitism genes Hgsyv46, Hg4e02 and Hg5d08 were identified and similarly expressed within the esophageal glands cells of Heterodera schachtii. Constitutive expression of Hs4E02 and Hs5D08 in transgenic Arabidopsis thaliana did not produce any visible phenotypic changes in plant growth and development nor affect the number of H. schachtii females that developed on roots of those plants. Constitutive and nematode-inducible Arabidopsis expression of double-stranded RNA complementary to Hssyv46, a parasitism gene with function similar to plant CLAVATA3/ESR peptides, resulted in a significant (P less than or equal to 0.05) 36% decrease in H. schachtii female numbers and significant host-derived RNA interference-mediated silencing of Hssyv46 transcript levels in nematodes excised from those roots. Significant and specific effects of Arabidopsis host-derived RNAi complementary to Hs5d08 or Hs4e02 on H. schachtii female development were not observed, however, up to 20% reduction in H. schachtii female numbers were observed in roots of these plants.
MafB negatively regulates RANKL-mediated osteoclast differentiation (2006)

Receptor activator of nuclear factor kappaB ligand (RANKL) induces osteoclast formation from hematopoietic cells via regulation of various transcription factors. Here, we show that MafB negatively regulates RANKL-induced osteoclast differentiation. Expression levels of MafB are significantly reduced by RANKL during osteoclastogenesis. Overexpression of MafB in bone marrow-derived monocyte/macrophage lineage cells (BMMs) inhibits the formation of TRAP(+) multinuclear osteoclasts, but phagocytic activity of BMMs is retained. Furthermore, overexpression of MafB in BMMs attenuates the gene induction of NFATc1 and osteoclast-associated receptor (OSCAR) during RANKL-mediated osteoclastogenesis. In addition, MafB proteins interfere with the DNA-binding ability of c-Fos, Mitf, and NFATc1, inhibiting their transactivation of NFATc1 and OSCAR. Furthermore, reduced expression of MafB by RNAi enhances osteoclastogenesis and increases expression of NFATc1 and OSCAR. Taken together, our results suggest that MafB can act as an important modulator of RANKL-mediated osteoclastogenesis.
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer (2016)

In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov number, NCT02142738 .).
Bronchial Epithelium as a Key Regulator of Airway Allergen Sensitization and Remodeling in Asthma (2000)

Asthma is a chronic inflammatory disorder of the airways manifesting as intermittent airflow limitation, which over time may become progressive (1). Both in the allergic and nonallergic forms of the disease there is evidence of an altered local T cell response in favor of Th2 cytokine release resulting in B cell isotype switching to IgE; mast cell, eosinophil, and basophil recruitment; and activation and release of a wide range of inflammatory mediators (2). However, it has become clear that, by itself, inflammation is not able to explain many of the features characteristic of chronic asthma and that restructuring of the airway wall is also required (3). This “remodeling” response presumably accounts for the incomplete therapeutic efficacy of corticosteroids, with persistence of bronchial hyperresponsiveness (BHR), and the progressive decline in pulmonary function over time that occurs in those asthmatic individuals with more chronic and severe disease (1). Although atopy, the propensity to generate allergen-specific IgE, is one of the strongest risk factors for asthma, especially in children and young adults, only 10% of atopics develop chronic asthma and, as adults, asthma occurs in the absence of atopy, most notably in those with more severe and chronic disease. It seems plausible that, rather than IgE-mediated inflammation being the initiator of disordered airway function, the epithelium itself is abnormal and it is this that predisposes the individual with asthma toward local allergen sensitization, and the injurious effects of respiratory viruses and air pollutants (including tobacco smoke). A disordered epithelium could also provide a basis for airway remodeling in asthma.
Interaction of Radicicol with Members of the Heat Shock Protein 90 Family of Molecular Chaperones (1999)

The Hsp90 family of proteins in mammalian cells consists of Hsp90 alpha and beta, Grp94, and Trap-1 (Hsp75). Radicicol, an antifungal antibiotic that inhibits various signal transduction proteins such as v-src, ras, Raf-1, and mos, was found to bind to Hsp90, thus making it the prototype of a second class of Hsp90 inhibitors, distinct from the chemically unrelated benzoquinone ansamycins. We have used two novel methods to immobilize radicicol, allowing for detailed analyses of drug-protein interactions. Using these two approaches, we have studied binding of the drug to N-terminal Hsp90 point mutants expressed by in vitro translation. The results point to important drug contacts with amino acids inside the N-terminal ATP/ADP-binding pocket region and show subtle differences when compared with geldanamycin binding. Radicicol binds more strongly to Hsp90 than to Grp94, the Hsp90 homolog that resides in the endoplasmic reticulum. In contrast to Hsp90, binding of radicicol to Grp94 requires both the N-terminal ATP/ADP-binding domain as well as the adjacent negatively charged region. Radicicol also specifically binds to yeast Hsp90, Escherichia coli HtpG, and a newly described tumor necrosis factor receptor-interacting protein, Trap-1, with greater homology to bacterial HtpG than to Hsp90. Thus, the radicicol-binding site appears to be specific to and is conserved in all members of the Hsp90 family of molecular chaperones from bacteria to mammals, but is not present in other molecular chaperones with nucleotide-binding domains.
Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin (2012)

Malaria, caused by Plasmodium sp , results in almost one million deaths and over 200 million new infections annually. The World Health Organization has recommended that artemisinin-based combination therapies be used for treatment of malaria. Artemisinin is a sesquiterpene lactone isolated from the plant Artemisia annua . However, the supply and price of artemisinin fluctuate greatly, and an alternative production method would be valuable to increase availability. We describe progress toward the goal of developing a supply of semisynthetic artemisinin based on production of the artemisinin precursor amorpha-4,11-diene by fermentation from engineered Saccharomyces cerevisiae , and its chemical conversion to dihydroartemisinic acid, which can be subsequently converted to artemisinin. Previous efforts to produce artemisinin precursors used S. cerevisiae S288C overexpressing selected genes of the mevalonate pathway [Ro et al. (2006) Nature 440:940–943]. We have now overexpressed every enzyme of the mevalonate pathway to ERG20 in S. cerevisiae CEN.PK2, and compared production to CEN.PK2 engineered identically to the previously engineered S288C strain. Overexpressing every enzyme of the mevalonate pathway doubled artemisinic acid production, however, amorpha-4,11-diene production was 10-fold higher than artemisinic acid. We therefore focused on amorpha-4,11-diene production. Development of fermentation processes for the reengineered CEN.PK2 amorpha-4,11-diene strain led to production of &gt; 40 g/L product. A chemical process was developed to convert amorpha-4,11-diene to dihydroartemisinic acid, which could subsequently be converted to artemisinin. The strains and procedures described represent a complete process for production of semisynthetic artemisinin.
The murine rac1 gene: cDNA cloning, tissue distribution and regulated expression of rac1 mRNA by disassembly of actin microfilaments. (1991)

A 886 bp cDNA encoding the murine rac1 protein has been isolated. The abundance of rac1 mRNA was determined in fourteen tissues from both mouse and pig. The mRNA 5' non-coding sequence is very rich in G + C, and has the potential to form several stable secondary structures. In addition, this region contains a putative open reading frame of 57 amino acids. Disruption of the actin microfilament network by cytochalasin B in LLC-PK1 cells results in down regulation of rac1 mRNA. In agreement with the proposed role of rac1 in exocytosis, these results could explain the inhibitory effect of cytochalasin B on secretory processes.
Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases (2016)

Mitogen-activated protein kinase (MAPK)-activated protein kinase (MK2) is exclusively regulated by p38 MAPK in vivo. Upon activation of p38 MAPK, MK2 binds with p38 MAPK, leading to phosphorylation of TTP, Hsp27, Akt, and Cdc25 that are involved in regulation of various essential cellular functions. In this review, we discuss current knowledge about molecular mechanisms of MK2 in regulation of TNF-α production, NADPH oxidase activation, neutrophil migration, and DNA-damage-induced cell cycle arrest which are involved in the molecular pathogenesis of acute lung injury, pulmonary fibrosis, and non-small-cell lung cancer. Collectively current and emerging new information indicate that developing MK2 inhibitors and blocking MK2-mediated signal pathways are potential therapeutic strategies for treatment of inflammatory and fibrotic lung diseases and lung cancer.