gebhart/patrepeval huggingface dataset:
Intravascular photoacoustic imaging using an IVUS imaging catheter (2007)

Catheter-based imaging of atherosclerosis with high resolution, albeit invasive, is extremely important for screening and characterization of vulnerable plaques. Currently, there is a need for an imaging technique capable of providing comprehensive morphological and functional information of plaques. In this paper, we present an intravascular photoacoustic imaging technique to characterize vulnerable plaques by using optical absorption contrast between normal tissue and atherosclerotic lesions. Specifically, we investigate the feasibility of obtaining intravascular photoacoustic (IVPA) images using a high-frequency intravascular ultrasound (IVUS) imaging catheter. Indeed, the combination of IVPA imaging with clinically available IVUS imaging may provide desired functional and morphological assessment of the plaque. The imaging studies were performed with tissue-mimicking arterial vessel phantoms and excised samples of rabbit artery. The results of our study suggest that catheter-based intravascular photoacoustic imaging is possible, and the combination of IVPA with IVUS has the potential to detect and differentiate atherosclerosis based on both the structure and composition of the plaque.
Signal attenuation and localization in optical coherence tomography studied by Monte Carlo simulation (1998)

A Monte Carlo model has been developed for optical coherence tomography (OCT). A geometrical optics implementation of the OCT probe with low-coherence interferometric detection was combined with three-dimensional stochastic Monte Carlo modelling of photon propagation in the homogeneous sample medium. Optical properties of the sample were selected to simulate intralipid and blood, representing moderately (g = 0.7) and highly (g = 0.99) anisotropic scattering respectively. For shallow optical depths in simulated intralipid (<3 scattering mean free path (mfp) units), the number of detected backscattered photons followed the extinction-single-backscatter model, and OCT was found to detect only minimally scattered photons. Within this depth range the backscatter positions of detected photons corresponded well with the nominal focus position of the probe. For propagation to deeper positions in intralipid, localization of backscattering was quickly lost due to detection of stray photons, and the number of detected photons remained constant with increasing depth in the non-absorbing medium. For strongly forward-directed scattering in simulated blood, the number of detected photons approached the extinction-single-backscatter model only for very shallow depths (<2 mfp units). However, backscattering positions for detected photons correlated well with the nominal focus position of the probe even for optical depths greater than 40 mfp units.
The Manganese Transporter MntH Is a Critical Virulence Determinant forBrucella abortus2308 in Experimentally Infected Mice (2009)

The gene designated BAB1_1460 in the Brucella abortus 2308 genome sequence is predicted to encode the manganese transporter MntH. Phenotypic analysis of an isogenic mntH mutant indicates that MntH is the sole high-affinity manganese transporter in this bacterium but that MntH does not play a detectable role in the transport of Fe(2+), Zn(2+), Co(2+), or Ni(2+). Consistent with the apparent selectivity of the corresponding gene product, the expression of the mntH gene in B. abortus 2308 is repressed by Mn(2+), but not Fe(2+), and this Mn-responsive expression is mediated by a Mur-like repressor. The B. abortus mntH mutant MWV15 exhibits increased susceptibility to oxidative killing in vitro compared to strain 2308, and a comparative analysis of the superoxide dismutase activities present in these two strains indicates that the parental strain requires MntH in order to make wild-type levels of its manganese superoxide dismutase SodA. The B. abortus mntH mutant also exhibits extreme attenuation in both cultured murine macrophages and experimentally infected C57BL/6 mice. These experimental findings indicate that Mn(2+) transport mediated by MntH plays an important role in the physiology of B. abortus 2308, particularly during its intracellular survival and replication in the host.
Molecular cloning of geranyl diphosphate synthase and compartmentation of monoterpene synthesis in plant cells (2000)

The nature of isoprenoids synthesized in plants is primarily determined by the specificity of prenyltransferases. Several of these enzymes have been characterized at the molecular level. The compartmentation and molecular regulation of geranyl diphosphate (GPP), the carbon skeleton that is the backbone of myriad monoterpene constituents involved in plant defence, allelopathic interactions and pollination, is poorly understood. We describe here the cloning and functional expression of a GPP synthase (GPPS) from Arabidopsis thaliana. Immunohistological analyses of diverse non-secretory and secretory plant tissues reveal that GPPS and its congeners, monoterpene synthase, deoxy-xylulose phosphate synthase and geranylgeranyl diphosphate synthase, are equally compartmentalized and distributed in non-green plastids as well in chloroplasts of photosynthetic cells. This argues that monoterpene synthesis is not solely restricted to specialized secretory structures but can also occur in photosynthetic parenchyma. These data provide new information as to how monoterpene biosynthesis is compartmentalized and induced de novo in response to biotic and abiotic stress in diverse plants.
Dolutegravir in antiretroviral-naive adults with HIV-1 (2013)

Throughout the 96 weeks of the SPRING-1 study, DTG demonstrated sustained efficacy and favorable safety/tolerability in treatment-naive individuals with HIV-1.
Familial aggregation ofV˙o 2 max response to exercise training: results from the HERITAGE Family Study (1999)

The aim of this study was to test the hypothesis that individual differences in the response of maximal O(2) uptake (VO(2max)) to a standardized training program are characterized by familial aggregation. A total of 481 sedentary adult Caucasians from 98 two-generation families was exercise trained for 20 wk and was tested for VO(2max) on a cycle ergometer twice before and twice after the training program. The mean increase in VO(2max) reached approximately 400 ml/min, but there was considerable heterogeneity in responsiveness, with some individuals experiencing little or no gain, whereas others gained >1.0 l/min. An ANOVA revealed that there was 2.5 times more variance between families than within families in the VO(2max) response variance. With the use of a model-fitting procedure, the most parsimonious models yielded a maximal heritability estimate of 47% for the VO(2max) response, which was adjusted for age and sex with a maternal transmission of 28% in one of the models. We conclude that the trainability of VO(2max) is highly familial and includes a significant genetic component.
Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. (1991)

Since high-affinity adenosine A2 receptors (A2a) are localized exclusively in dopamine-rich regions in the central nervous system and mediate inhibition of locomotor activity, we have examined the effect of A2a receptor activation on D1 and D2 receptor binding in membrane preparations of the rat striatum. The A2a agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'- N-ethylcarboxamidoadenosine (CGS 21680) increased the Kd of the dopamine D2 agonist L-(-)-N-[3H]propylnorapomorphine without affecting the Bmax. The increase in Kd was maximal (40%) at 30 nM CGS 21680. CGS 21680 (30 nM) decreased the dopamine-induced inhibition of [3H]raclopride (a D2 antagonist) binding due to an increase (about 3-fold) in KH and KL, the dissociation constants of high- and low-affinity binding sites. The effects of CGS 21680 were antagonized by the adenosine antagonist 8-phenyltheophylline (10 microM). (-)-N6-(2-Phenylisopropyl)adenosine produced an effect similar to that of CGS 21680, provided the concentration used was high enough to stimulate A2a receptors (300 nM). GTP (50 microM) also decreased the dopamine-induced inhibition of [3H]raclopride binding but, in contrast to CGS 21680, GTP decreased the proportion of D2 receptors in the high-affinity state. CGS 21680 (30 nM) did not affect the Kd or Bmax of [3H]raclopride and failed to affect ligand binding to D1 receptors. Thus, stimulation of A2a receptors potently reduces the affinity of D2 agonist binding sites within the plasma membrane of striatal neurons. This A2a-D2 interaction may underlie the neuroleptic-like actions of adenosine agonists and the enhancing effects of adenosine antagonists, such as caffeine, on locomotor activity.
Influence of chronic ethanol consumption on the metabolism and carcinogenicity of tobacco-related nitrosamines. (1982)

The effect of chronic ethanol consumption by Syrian golden hamsters (SGH) on the carcinogenicity and target tissue metabolism of N-nitroso-pyrrolidine (NPYR) and N'-nitrosonornicotine (NNN) has been examined. Ethanol-consuming hamsters treated with NPYR developed more nasal cavity and tracheal tumours than controls. Ethanol consumption did not affect the carcino-genicity of NNN. When the metabolism of NPYR and NNN by isolated tracheal rings was examined, it was observed that tracheal rings isolated from ethanol-consuming SGH metabolized NPYR at a higher rate than similar preparations from control animals. In contrast, no differences in the rates of metabolism of NNN were observed.
THGS: a web-based database of Transmembrane Helices in Genome Sequences (2003)

Transmembrane Helices in Genome Sequences (THGS) is an interactive web-based database, developed to search the transmembrane helices in the user-interested gene sequences available in the Genome Database (GDB). The proposed database has provision to search sequence motifs in transmembrane and globular proteins. In addition, the motif can be searched in the other sequence databases (Swiss-Prot and PIR) or in the macromolecular structure database, Protein Data Bank (PDB). Further, the 3D structure of the corresponding queried motif, if it is available in the solved protein structures deposited in the Protein Data Bank, can also be visualized using the widely used graphics package RASMOL. All the sequence databases used in the present work are updated frequently and hence the results produced are up to date. The database THGS is freely available via the world wide web and can be accessed at http:// pranag.physics.iisc.ernet.in/thgs/ or http://144.16. 71.10/thgs/.
Pharmacokinetics of the mouse monoclonal antibody 17-1A in cancer patients receiving various treatment schedules. (1990)

Twenty-four patients with metastatic colorectal carcinoma were treated with repeated doses (200-500 mg) of the mouse monoclonal antibody (MAb) 17-1A. Four different treatment schedules were used. The total dose was 1, 3.6, 7.6, and 12 g, respectively. Altogether, 263 infusions were administered. The interindividual variations in the maximum serum concentration at 2 h (max2 h) were large. The mean max2 h value after an infusion of 200 mg was 55 +/- 5 micrograms/ml and after 500 mg, 132 +/- 7 micrograms/ml. Max2 h concentration correlated inversely with the half-life of MAb 17-1A (P less than 0.001). The t1/2 beta for 200 mg was 25.9 +/- 1.4 h and after the administration of 500 mg, 19.8 +/- 1.0 h. The total area under the concentration versus time curve increased when high doses were administered on a continuous basis, in comparison with spaced infusions, thus increasing the exposure of the tumor tissues to MAb 17-1A. The pharmacokinetics of mouse MAb 17-1A are best described by a one-compartment model. All patients developed anti-mouse IgG antibodies and most also IgM antibodies. In the more intensive treatment schedules, the IgG antibody response was suppressed. Induction of high titers of anti-mouse antibodies did not cause clinical problems. Neither did they affect the pharmacokinetics of MAb 17-1A at these dose levels. Therapy was tolerated well. The side effects were mild and of short duration. The gastrointestinal adverse reactions were dose dependent and correlated to serum max2 h concentration. Allergic reactions were rare and easily clinically manageable.
Automated high resolution optical mapping using arrayed, fluid-fixed DNA molecules (1998)

New mapping approaches construct ordered restriction maps from fluorescence microscope images of individual, endonuclease-digested DNA molecules. In optical mapping, molecules are elongated and fixed onto derivatized glass surfaces, preserving biochemical accessibility and fragment order after enzymatic digestion. Measurements of relative fluorescence intensity and apparent length determine the sizes of restriction fragments, enabling ordered map construction without electrophoretic analysis. The optical mapping system reported here is based on our physical characterization of an effect using fluid flows developed within tiny, evaporating droplets to elongate and fix DNA molecules onto derivatized surfaces. Such evaporation-driven molecular fixation produces well elongated molecules accessible to restriction endonucleases, and notably, DNA polymerase I. We then developed the robotic means to grid DNA spots in well defined arrays that are digested and analyzed in parallel. To effectively harness this effect for high-throughput genome mapping, we developed: (i) machine vision and automatic image acquisition techniques to work with fixed, digested molecules within gridded samples, and (ii) Bayesian inference approaches that are used to analyze machine vision data, automatically producing high-resolution restriction maps from images of individual DNA molecules. The aggregate significance of this work is the development of an integrated system for mapping small insert clones allowing biochemical data obtained from engineered ensembles of individual molecules to be automatically accumulated and analyzed for map construction. These approaches are sufficiently general for varied biochemical analyses of individual molecules using statistically meaningful population sizes.
Fetal cells in the maternal circulation: isolation by multiparameter flow cytometry and confirmation by polymerase chain reaction (1991)

During pregnancy, nucleated fetal erythrocytes enter the maternal circulation and can be isolated efficiently from the maternal cells by multiparameter flow cytometry. Male DNA, implying presence of a male fetus, can be identified in flow-sorted maternal blood by polymerase chain reaction with oligonucleotide primers flanking single-copy Y-specific DNA sequences. Among flow-sorted samples, we correctly identified fetal sex in 17/18 (94%) pregnancies of 10-21 weeks gestation. Maternal blood thus provides a potential opportunity for prenatal diagnosis that could preclude the need for invasive procedures in current use.
Pathophysiology of peroxisomal beta-oxidation. (1989)

Mammalian peroxisomes are subcellular organelles involved in the metabolism of hydrogen peroxide (oxidases, catalase), lipid anabolism (ether lipid biosynthesis) and catabolism (oxidation of fatty acids and fatty acid derivatives), and intermediary metabolism (transaminases, dehydrogenases). Peroxisomes are formed by division, as is the case for mitochondria, but, in contrast to these organelles, they do not contain DNA. They were discovered and characterized (by biochemical and morphological techniques) later than the majority of the other cell components and specific procedures have been developed for their isolation. Functions of peroxisomes are, as a rule, shared by other cell compartments so that specific enzyme assays have also been developed. Combination of specific isolation procedures, enzyme assays and morphological analysis have resulted in our current knowledge of peroxisomal physiology which, however, has greatly benefited, as in the case of lysosomes, from the study of inborn errors of metabolism and the contribution of molecular biology. Novel enzymes and metabolic pathways have been demonstrated to exist in peroxisomes and human genetic disorders affecting one or several of these functions have been recognized.
Pursuing “Zero” Protein Adsorption of Poly(carboxybetaine) from Undiluted Blood Serum and Plasma (2009)

Human blood serum and plasma pose significant challenges to blood-contacting devices and implanted materials because of their high nonspecific adsorption onto surfaces. In this work, we investigated nonspecific protein adsorption from single protein solutions and complex media such as undiluted human blood serum and plasma onto poly(carboxybetaine acrylamide) (polyCBAA)-grafted surfaces at different temperatures. The polyCBAA grafting was done via atom-transfer radical polymerization (ATRP) with varying film thicknesses. The objective is to create a surface that experiences "zero" protein adsorption from complex undiluted human blood serum and plasma. Results show that protein adsorption from undiluted human blood serum, plasma, and aged serum on the polyCBAA-grafted surface is undetectable at both 25 and 37 degrees C by a surface plasmon resonance (SPR) sensor. This was achieved with a film thickness of approximately 21 nm. Furthermore, it is demonstrated that the polyCBAA surfaces after antibody immobilization maintain undetectable protein adsorption from undiluted human blood serum. This is the first time that an effective nonfouling material suitable for applications in complex blood media has been demonstrated.
Determinación de los valores de los factores de diseño para la obtención de productos robustos. Aplicación al caso de un circuito con bobina y resistencia: aplicación al caso de un circuito con bobina y resistencia (1995)

Frente a la vision antigua de controlar la calidad mediante la inspeccion final, o la clasica del control estadistico del proceso, la forma que actualmente podriamos denominar moderna, y desde luego la mas economica de asegurar la calidad, consiste en disenar productos tales que sus prestaciones se mantengan en el nivel deseado aunque estos no se hayan fabricado en las condiciones mas adecuadas, o se hayan elaborado con materias primas que no reunan las condiciones optimas, o bien que sean utilizados en condiciones distintas a las previstas.
A estos productos se les denomina robustos, y en este articulo se presenta, a traves de un caso concreto, una nueva metodologia para la seleccion de los valores de sus parametros.
Matrigel induces thymosin β4 gene in differentiating endothelial cells (1995)

We performed differential cDNA hybridization using RNA from endothelial cells cultured for 4 hours on either plastic or basement membrane matrix (Matrigel), and identified early genes induced during the morphological differentiation into capillary-like tubes. The mRNA for one clone, thymosin beta 4, was increased 5-fold. Immunostaining localized thymosin beta 4 in vivo in both growing and mature vessels as well as in other tissues. Endothelial cells transfected with thymosin beta 4 showed an increased rate of attachment and spreading on matrix components, and an accelerated rate of tube formation on Matrigel. An antisense oligo to thymosin beta 4 inhibited tube formation on Matrigel. The results suggest that thymosin beta 4 is induced and likely involved in differentiating endothelial cells. Thymosin beta 4 may play a role in vessel formation in vivo.
Free energy relationships for thiol-disulfide interchange reactions between charged molecules in 50% methanol. (1984)

Acid dissociation equilibrium constants and rate constants for disulfide interchange reactions have been measured in 50% methanol at low ionic strength for peptides containing cysteines with local ionic neighboring groups. These physical constants may be correlated by separation of free energy contributions into solvent-independent and solvent-dependent factors. The former represent inductive effects which may be evaluated by extrapolation of pKa values to the limit of infinite ionic strength. These solvent-independent contributions give Br onsted coefficients consistent with previously reported values for disulfides with neutral constituents. The solvent-dependent contributions represent thru-solvent electrostatic effects and are consistent with the form of the Bjerrum relationship correlating molecular charges, intergroup distances, and the dielectric constant of the solvent. These results provide a quantitative framework for developing strategies for employing coulombic interactions to direct disulfide pairing in synthetic polypeptides.
Elements distinct from human immunodeficiency virus type 1 splice sites are responsible for the Rev dependence of env mRNA (1994)

In the absence of the viral regulatory protein Rev, the human immunodeficiency virus type 1 gag/pol and env mRNAs are inefficiently expressed, since nucleocytoplasmic transport, stability, and polysomal loading are impaired. It has been suggested that splicing is necessary for Rev function and that the low expression of the unspliced and intermediate spliced mRNAs in the absence of Rev is associated with specific splice sites. Previous studies identified distinct RNA elements within the gag/pol region responsible for low expression that are not associated with splice sites. Here we study the determinants for Rev dependence of the authentic env mRNA. We demonstrate that upon removal of all the utilized splice sites, the env mRNA is still Rev dependent and Rev responsive for expression in human cells. We have identified several regions within the env mRNA that inhibit expression of a gag-env hybrid mRNA. Elimination of one of these elements, located within the Rev-responsive element, did not result in virus expression, supporting our model that several independently acting elements are responsible for the downregulatory effect. By analogy to the RNA elements within the gag/pol region, we propose that elements unrelated to utilized splice sites are responsible for the posttranscriptional regulation of env mRNA.
Functional activation of the cystic fibrosis trafficking mutant delta F508-CFTR by overexpression (1995)

The most common mutation in the gene associated with cystic fibrosis (CF) causes deletion of phenylalanine at residue 508 (delta F508) of the gene product called CFTR. This mutation results in the synthesis of a variant CFTR protein that is defective in its ability to traffic to the plasma membrane. Because earlier studies showed delta F508-CFTR retains significant phosphorylation-regulated chloride (Cl-) channel activity, processes capable of restoring the mislocalized delta F508-CFTR to the correct cellular destination may have therapeutic benefit. Here we report one such process that involves overexpression of the mutant protein and appears to result in the escape of a small amount of delta F508-CFTR to the plasma membrane. In recombinant cells where expression of delta F508-CFTR is controlled by the metallothionein promoter, this effect can be brought about by treatment with sodium butyrate. Although cAMP-activated Cl- channel activity could also be detected in immortalized human airway epithelial cells homozygous for the delta F508 mutation at the single cell level, treatment with butyrate did not generate a measurable cAMP-stimulated Cl- current in polarized monolayers of primary CF airway epithelia. However, the observation that overexpression can effect the presence of recombinant delta F508-CFTR at the plasma membrane suggests that perhaps other butyrate-like compounds that are more potent and more specific for the promoter of the CF gene may be efficacious in alleviating the Cl- channel defect associated with CF.
Hyperuricaemia and Long-Term Outcome After Hospital Discharge in Acute Heart Failure Patients (2006)

In hospitalized patients with acute HF and LV systolic dysfunction, hyperuricaemia is a long-term prognostic marker for death and/or new HF readmission.