gebhart/patrepeval huggingface dataset:
Nutritional therapy improves function and complements corticosteroid intervention in <i>mdx</i> mice (2005)

Corticosteroid therapy for Duchenne muscular dystrophy is effective but associated with long-term side effects. To determine the potential therapeutic benefit from four nutritional compounds (creatine monohydrate, conjugated linoleic acid, alpha-lipoic acid, and beta-hydroxy-beta-methylbutyrate) alone, in combination, and with corticosteroids (prednisolone), we evaluated the effects on several variables in exercising mdx mice. Outcome measures included grip strength, rotarod performance, serum creatine kinase levels, muscle metabolites, internalized myonuclei, and retroperitoneal fat pad weight. In isolation, each nutritional treatment showed some benefit, with the combination therapy showing the most consistent benefits. Prednisolone and the combination therapy together provided the most consistent evidence of efficacy; increased peak grip strength (P < 0.05), decreased grip strength fatigue (P < 0.05), decreased number of internalized myonuclei (P < 0.01), and smaller retroperitoneal fat pad stores (P < 0.001). This study provided evidence for therapeutic benefit from a four-compound combination therapy alone, and in conjunction with corticosteroids in the mdx model of DMD.
Interface fluid syndrome in laser in situ keratomileusis after complicated trabeculectomy (2006)

A 69-year-old man developed stromal edema and a pocket of fluid in the laser in situ keratomileusis (LASIK) interface wound in the left eye after acute endothelial cell loss from complicated trabeculectomy. He eventually required penetrating keratoplasty along with cataract surgery. Histologic examination of the corneal button showed an edematous 720 microm central residual stromal bed, a 54 microm empty space at the level of the central interface wound, and a 154 microm LASIK flap. The endothelial cell count was 0 to 2 cells per high-power field, corresponding to a cell density of 450 to 500 cells/mm(2). Four years after LASIK, the central interface wound was susceptible to forming a pocket of serous fluid after the corneal endothelial function was compromised.
Monolithic integration of an AlGaAs/GaAs multiple quantum well distributed feedback laser and a grating coupler for surface emission (1987)

Monolithically integrated surface-emitting device consisting of an AlGaAs/GaAs multiple quantum well distributed feedback laser and a grating coupler is demonstrated for the first time. The grating coupler was made by utilizing the properties of low loss and easily saturable absorption in the multiple quantum well structure. No additional crystal growths or complicated fabrication processes were required for the integration. An output power of 2 mW and a narrow beam divergence of 0.22° were obtained under continuous wave operation.
Guanosine pentaphosphate and guanosine tetraphosphate accumulation and induction of Myxococcus xanthus fruiting body development (1980)

Development of multicellular fruiting bodies of Myxococcus xanthus can be induced by limitation of any of a number of different classes of amino acids. Investigated were amino acids that wild-type strains of M. xanthus are unable to synthesize (isoleucine, leucine, and valine), can synthesize at a low rate (phenylalanine), or can normally synthesize at an adequate rate (tryptophan and serine). In general, gradual rather than abrupt starvation for an essential amino acid was required for the induction of fruiting. Perhaps gradual starvation in general minimizes antagonism between amino acids present in the medium, as was documented for valine starvation. The previously reported induction of fruiting by a high concentration of threonine was shown to be specifically reversed by lysine. Threonine addition may starve cells for lysine by feedback inhibition of aspartokinase activity. Starvation for carbon-energy sources or inorganic phosphate also induced fruiting. As in other bacteria, amino acid starvation of M. xanthus leads to increases in cellular guanosine polyphosphate, usually consisting of large increases in the amount of guanosine pentaphosphate with smaller increases in the level of guanosine tetraphosphate. Guanosine polyphosphate accumulation is thus shown to be correlated with nutritional conditions that induce fruiting, and therefore may serve as an intracellular signal to trigger cells to end vegetative growth and initiate fruiting body development.
Tissue-Specific Cultured Human Pericytes: Perivascular Cells from Smooth Muscle Tissue Have Restricted Mesodermal Differentiation Ability (2016)

Microvascular pericytes (PCs) are considered the adult counterpart of the embryonic mesoangioblasts, which represent a multipotent cell population that resides in the dorsal aorta of the developing embryo. Although PCs have been isolated from several adult organs and tissues, it is still controversial whether PCs from different tissues exhibit distinct differentiation potentials. To address this point, we investigated the differentiation potentials of isogenic human cultured PCs isolated from skeletal (sk-hPCs) and smooth muscle tissues (sm-hPCs). We found that both sk-hPCs and sm-hPCs expressed known pericytic markers and did not express endothelial, hematopoietic, and myogenic markers. Both sk-hPCs and sm-hPCs were able to differentiate into smooth muscle cells. In contrast, sk-hPCs, but not sm-hPCs, differentiated in skeletal muscle cells and osteocytes. Given the reported ability of the Notch pathway to regulate skeletal muscle and osteogenic differentiation, sk-hPCs and sm-hPCs were treated with N-[N-(3,5- difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a known inhibitor of Notch signaling. DAPT treatment, as assessed by histological and molecular analysis, enhanced myogenic differentiation and abolished osteogenic potential of sk-hPCs. In contrast, DAPT treatment did not affect either myogenic or osteogenic differentiation of sm-hPCs. In summary, these results indicate that, despite being isolated from the same anatomical niche, cultured PCs from skeletal muscle and smooth muscle tissues display distinct differentiation abilities.
Biochemical and Biophysical Characterization of Type I Retinal Binding Proteins for their Application in Device Electronics (2011)

Type I retinal binding proteins are simple photoactive membrane proteins that translocate ions against a chemical gradient to serve a biological function. Harnessing the photophysical properties of two such proton pumps, Bacteriorhodopsin (BR) and Proteorhodopsin (PR), is of interest for application in biophotonic (e.g., volumetric and associative memories) and biomimetic (e.g., artificial retina) technologies. Proteorhodopsin, a recently discovered cubacterial rhodopsin, is found throughout the oceans of the Earth and exhibits many similarities with BR, which has long been the paradigm of protein based device electronics. Many of the current biochemical and biophysical studies of PR use a detergent solubilized form of the protein that is expressed in Escherichia coli. The first half of this thesis characterizes the structural and photochemical properties of PR in non-ionic detergent and various nanoscale phospholipid bilayers, or so-called nanodisc structures. These studies demonstrate that the detergent solubilized protein is both photochemically (9,000 to 70,000 photocycles protein -1) and thermally (>75 °C) stable. Incorporation of PR into small or large nanodiscs demonstrates that PR exists as a photoactive oligomer that exhibits a moderately fast photocycle (∼ 100 ins) in thick phospholipid bilayer. The second half of this thesis characterizes a novel blue BR mutant (i.e., D85E/D96Q) that is capable of forming the Q state photoproduct with >99% efficiency at pH 8.5. The Q photoproduct is the basis of several biophotonic technologies that employ BR as the photoactive element, but have yet to be practical because of the low Q formation efficiency from native and mutant BRs. The D85E/D96Q mutant also exhibits higher synthesis yields of the stable protein and the greatest stability of all investigated blue BR mutants. ^
P2‐191: Three dimensional structure of signal peptide peptidase (2009)

γ-Secretase is a membrane-embedded protease that executes an intramembrane proteolysis in the production of amyloid β-peptide. Regulation of the γ-secretase activity is an important pharmaceutical strategy. However, as γ-secretase is a gigantic membrane protein complex comprised of presenilin, nicastrin, APH-1 and PEN-2, the fine structure of the active complex still remains unclear. In this regard, signal peptide peptidase (SPP) can model the structure of the γ-secretase-mediated processing: SPP and presenilin, the latter being the catalytic subunit of the γ-secretase complex, harbor similar active site motifs and are inhibited by the same set of aspartyl protease transition-state analogue inhibitors. Moreover, recent studies suggest that SPP and γ-secretase share the same basic mechanism in the intramembrane proteolysis. To gain insight into the structure-function relationship of SPP, we expressed 3xFLAG-tagged human SPP by Spodoptera frugiperda Sf9 insect cells/baculovirus expression system and purified it by anti-FLAG M2-agarose column from DDM solubilized membrane fraction. Purified SPP were then separated by size exclusion chromatography. SPP activity in each fraction was monitored by in vitro assay using a synthetic peptide substrate. We found that SPP activities were mainly detected at a tetramer- (200 kDa) or doubled tetramer-size (400 kDa) molecular weight fractions. Moreover, not only purified 3xFLAG SPP, but endogenous human SPP as well as Drosophila SPP, were detected at a tetramer size in Blue-Native PAGE analysis, suggesting that active SPP forms tetramer in solubilized fraction. We then analyzed the negatively stained 3xFLAG human SPP by transmission electron microscopy. Relatively uniform particles were observed as major species in electron micrographs in fractions showing SPP activity. We collected ~5,000 images and reconstituted a three dimensional representation at 23 angstroms resolution. The structure of the purified SPP occupies a volume of 83 x 83 x 129 angstroms and a bullet-shaped structure forming rhombus face.
Temporal dependence of hyperthermic augmentation of macrophage-TNF production and tumor cell-TNF sensitization (1989)

Hyperthermia in the therapeutic (greater than or equal to 42-43 degrees C) and febrile (less than or equal to 39-40.5 degrees C) ranges modulated the cytotoxic activities of macrophages cocultured with tumour cells and of the monokine tumour necrosis factor (TNF) against tumour cells. These modulatory interactions had clear treatment-sequence dependencies, and some sequences markedly augmented cytotoxic activities. Heated murine bacillus Calmette-Guerin-activated macrophages retained their cytotoxic activities better in coculture with unheated tumour cells if triggering with the endotoxin lipopolysaccharide preceded 1 h of heating at 42 or 43 degrees C than they did if heating to the same extent was concomitant with, or preceded, triggering. Retention of cytotoxicity in coculture during 24 h of 39 or 40.5 degrees C heating was less dependent on pre-heating triggering. The triggering/heating sequence also had modulatory effects on the secretion by heated macrophages of TNF which is involved in cytotoxic manifestations in coculture. Production of TNF by macrophages heated for 1 h at 40.5-43 degrees C or 24 h at 39 or 40.5 degrees C was augmented 1.5- to 6-fold (depending on the heat dose) when triggering preceded heating, whereas sequences in which heating was concomitant with triggering or preceded triggering were detrimental to TNF secretion. Profound treatment-sequence dependencies were also seen when timing of the addition of recombinant human TNF was varied in relation to the heat treatment of tumour cells. Sensitization of TNF-responsive L-929 and TNF-resistant EMT-6 tumour cells occurred if monokine addition preceded heating, whereas the reverse treatment-sequence reduced or eliminated sensitization. Both tumour cell types were also sensitized to TNF if monokine treatment preceded 24 h heating at 40.5 degrees C. These results support the hypothesis that appropriately constructed sequences for either macrophage priming/triggering or monokine treatment of tumour cells, combined with hyperthermia, could augment the cytotoxic actions of macrophages and the cytotoxicity of endogenously added monokines.
A new look at reaction mechanisms with 4. pi. charged-particle and neutron multiplicity measurements (1987)

We have studied the excitation of target-like fragments produced in the reactions of 331.9 MeV /sup 28/Si + /sup 181/Ta. The light charged particles and intermediate mass fragments were detected in a small, highly segmented 4..pi.. phoswich detector system placed inside the spin spectrometer, a 4..pi.. NaI array which served as a neutron and ..gamma..-ray detector. All target emissions indicate that excitation ceases to increase with decreasing projectile-like fragment energy, as it should if the primary reaction is binary. Non-equilibrium neutron, proton and ..cap alpha..-particle emission and projectile fragmentation conspire and limit the conversion of kinetic energy into target excitation. This effect is more pronounced for PLF away from the injection point and for the largest kinetic energy losses. 8 refs., 10 figs.
Integration and stability of CHO amplicons containing plasmid sequences. (1992)

Fluorescence in situ hybridization (FISH, 15) and high density, non-selective long term perfusion culture were used to study aspects of genetic stability and productivity in recombinant CHO cells. We analysed the distribution and structure of recombinant amplicons in chromosomes of CHO cells used for the production of proteins. In the presence, but not in the absence, of methotrexate (MTX) we found a high proportion of cells (40-60%) with multiple and/or unusually structured and extended chromosome regions containing amplified sequences. Removal of MTX from culture media resulted in the rapid decline in the frequency of cells containing amplified sequences exhibiting multiple and heterogeneous integrations. In cloned lines cultivated in the absence of MTX, a well defined signal motif on a specific chromosome, interpreted as the "master integration" unit, became increasingly abundant over time until almost all cells contained that signal motif. We used fluorescence in situ hybridization (FISH) with chemically modified DNA probes complementary to the integrated sequences to verify the stability of master integrations in cells cultured for extended periods in medium lacking MTX. In a second approach, we studied long-term stability of recombinant sequences during non-selective perfusion culture of CHO populations with non-cloned, MTX resistant heterogeneous populations of cells producing CD4IgG chimeric molecules. Due to the mode of transfection and primary selection the resulting cell lines consisted of subpopulations of cells derived from various independent integration events. The amplification and MTX selection procedure used consecutively generated multiple, structurally different amplicon types in the cell population, thus increasing the degree of heterogeneity. High density perfusion culture of these cells in the absence of MTX was used to maximize growth rates and was thought to select against cells with reduced growth rates, due to the highly amplified state of their introduced DNA, with concomitantly high productivity. However we found no evidence for such a selection; cells showed no reduction in copy number or total loss of amplified sequences at the end of the culture. More significantly, specific productivity of these cell lines grown under non-selective conditions did not decrease over the 100 days observation period.
ALGORITHM OF COMPENSATING AN INERTIAL NAVIGATION SENSOR WITH A GPS RECEIVER (1995)

In vehicle navigation systems, the determination of vehicle location requires high accuracy to provide appropriate route-guidance by voice or some other method. With the price of gyros to detect a heading having been reduced for total cost reduction, a deterioration in directional accuracy has also occurred. To solve this problem, an algorithm is proposed to compensate a gyro with a global positioning system (GPS) receiver and a prototype is constructed. As a result, a level of directional detecting accuracy equal to that of advanced fiber-optic gyroscopes is achieved. This paper contains the general description of each adjustment method, and an evaluative result for location accuracy during actual traveling.
Cryptic Variation between Species and the Basis of Hybrid Performance (2010)

Crosses between closely related species give two contrasting results. One result is that species hybrids may be inferior to their parents, for example, being less fertile [1]. The other is that F1 hybrids may display superior performance (heterosis), for example with increased vigour [2]. Although various hypotheses have been proposed to account for these two aspects of hybridisation, their biological basis is still poorly understood [3]. To gain further insights into this issue, we analysed the role that variation in gene expression may play. We took a conserved trait, flower asymmetry in Antirrhinum, and determined the extent to which the underlying regulatory genes varied in expression among closely related species. We show that expression of both genes analysed, CYC and RAD, varies significantly between species because of cis-acting differences. By making a quantitative genotype-phenotype map, using a range of mutant alleles, we demonstrate that the species lie on a plateau in gene expression-morphology space, so that the variation has no detectable phenotypic effect. However, phenotypic differences can be revealed by shifting genotypes off the plateau through genetic crosses. Our results can be readily explained if genomes are free to evolve within an effectively neutral zone in gene expression space. The consequences of this drift will be negligible for individual loci, but when multiple loci across the genome are considered, we show that the variation may have significant effects on phenotype and fitness, causing a significant drift load. By considering these consequences for various gene-expression-fitness landscapes, we conclude that F1 hybrids might be expected to show increased performance with regard to conserved traits, such as basic physiology, but reduced performance with regard to others. Thus, our study provides a new way of explaining how various aspects of hybrid performance may arise through natural variation in gene activity.
Clinical severity of human infections with avian influenza A(H7N9) virus, China, 2013/14 (2014)

Assessing the severity of emerging infections is challenging because of potential biases in case ascertainment. The first human case of infection with influenza A(H7N9) virus was identified in China in March 2013; since then, the virus has caused two epidemic waves in the country. There were 134 laboratory-confirmed cases detected in the first epidemic wave from January to September 2013. In the second epidemic wave of human infections with avian influenza A(H7N9) virus in China from October 2013 to October 2014, we estimated that the risk of death among hospitalised cases of infection with influenza A(H7N9) virus was 48% (95% credibility interval: 42-54%), slightly higher than the corresponding risk in the first wave. Age-specific risks of death among hospitalised cases were also significantly higher in the second wave. Using data on symptomatic cases identified through national sentinel influenza-like illness surveillance, we estimated that the risk of death among symptomatic cases of infection with influenza A(H7N9) virus was 0.10% (95% credibility interval: 0.029-3.6%), which was similar to previous estimates for the first epidemic wave of human infections with influenza A(H7N9) virus in 2013. An increase in the risk of death among hospitalised cases in the second wave could be real because of changes in the virus, because of seasonal changes in host susceptibility to severe infection, or because of variation in treatment practices between hospitals, while the increase could be artefactual because of changes in ascertainment of cases in different areas at different times.
Diclofenac Increases Beta-Endorphin Plasma Concentrations (1984)

Plasma and ventricular cerebro-spinal fluid (CSF) Beta-endorphin concentrations were evaluated after chromatographic separation in patients carrying a ventricular shunt before and after the administration of diclofenac or placebo. In the same subjects the ventricular CSF concentrations of the serotonin and the catecholamine metabolites 5-hydroxyindole-acetic acid (5-HIAA), homovanillic acid (HVA) and MOPEG were also evaluated. Plasma, but not ventricular, Beta-endorphin concentrations increased significantly after diclofenac, while placebo was ineffective. No significant changes in ventricular 5-HIAA, HVA or MOPEG levels were observed. These data suggest a role for Beta-endorphin in the analgesic effect of diclofenac.
Cloning, Expression and Regulation of Angiotensin II Receptors (1994)

Angiotensin II isoform 1 (AT1) receptor cDNAs were cloned by expression cloning from bovine adrenal and rat vascular smooth muscles. Human AT1 receptor was also cloned. Seven transmembrane structures emerged. A single type of receptor seems to interact with more than one type of G-protein. AT1 consists of subtypes AT1A and AT1B, and the regulation of the receptors occurs at many stages. The isoform AT2 was also expression cloned from rat pheochromocytoma cells. Although its ligand binding is not affected by GTP analogs, it is a seven transmembrane domain receptor. It mediates the inhibition of phosphotyrosine phosphatase by angiotensin II and AT2 specific CGP42112A; the inhibition was abolished by pertussis toxin. Thus, AT2 belongs to a new class of angiotensin receptors with unique signalling and regulatory mechanisms.
CheY-dependent Methylation of the Asparagine Receptor, McpB, during Chemotaxis in Bacillus subtilis (1999)

For the Gram-positive organism Bacillus subtilis, chemotaxis to the attractant asparagine is mediated by the chemoreceptor McpB. In this study, we show that rapid net demethylation of B. subtilis McpB results in the immediate production of methanol, presumably due to the action of CheB. We also show that net demethylation of McpB occurs upon both addition and removal of asparagine. After each demethylation event, McpB is remethylated to nearly prestimulus levels. Both remethylation events are attributable to CheR using S-adenosylmethionine as a substrate. Therefore, no methyl transfer to an intermediate carrier need be postulated to occur during chemotaxis in B. subtilis as was previously suggested. Furthermore, we show that the remethylation of asparagine-bound McpB requires the response regulator, CheY-P, suggesting that CheY-P acts in a feedback mechanism to facilitate adaptation to positive stimuli during chemotaxis in B. subtilis. This hypothesis is supported by two observations: a cheRBCD mutant is capable of transient excitation and subsequent oscillations that bring the flagellar rotational bias below the prestimulus value in the tethered cell assay, and the cheRBCD mutant is capable of swarming in a Tryptone swarm plate.