gebhart/patrepeval huggingface dataset:
Reduced Hospitalization with Cardiovascular and Pulmonary Disease in Obstructive Sleep Apnea Patients on Nasal CPAP Treatment (1997)

Cardiovascular and pulmonary disease (CVPD) is common in patients with obstructive sleep apnea syndrome (OSAS). This retrospective study addressed the accumulated in-hospital time during 2 years prior to treatment with nasal continuous positive airway pressure (nCPAP) as compared to 2 years after initiating of nCPAP in patients with OSAS and CVPD. A cohort representing all patients (n = 88) receiving nCPAP during the period 1988-1994 at the Skövde Central Hospital, Skövde, Sweden, was studied. Data collection was based on interviews with patients as well as reviews of clinic charts. All hospitalizations and diagnostic codes by any type were thereby successfully gathered for the whole group. Six patients with confounding serious diseases were excluded from the analysis. A CVPD diagnosis (ICD-9, codes 401-435 and 490-496) was found in 54 out of 82 patients (66%), of whom 36 of 58 were nCPAP users (62%) and 18 of 24 were nonusers (75%). In 54 sleep apneics with CVPD, 31 were hospitalized acutely under one or more of these diagnostic codes during the study period of 4 years. The total number of in-hospital days due to CVPD in the nCPAP users (n = 19) before nCPAP prescription was 413 days (median 10, range 3-66) compared to 54 days (median 0, range 0-25) after nCPAP (p < 0.0001). The corresponding values for the nonuser group (n = 12) was 137 days (median 8.5, range 0-42) before and 188 days (median 9.5, range 0-47) after the nCPAP prescription (ns). We conclude that nCPAP treatment reduces the need for acute hospital admission due to CVPD in patients with OSAS. This reduction of concomitant health care consumption should be taken into consideration when assessing the cost-benefit evaluation of nCPAP therapy.
Trehalose metabolism in Escherichia coli: stress protection and stress regulation of gene expression (1993)

Endogenously synthesized trehalose is a stress protectant in Escherichia coli. Externally supplied trehalose does not serve as a stress protectant, but it can be utilized as the sole source of carbon and energy. Mutants defective in trehalose synthesis display an impaired osmotic tolerance in minimal growth media without glycine betaine, and an impaired stationary-phase-induced heat tolerance. Mechanisms for stress protection by trehalose are discussed. The genes for trehalose-6-phosphate synthase (otsA) and anabolic trehalose-6-phosphate phosphatase (otsB) constitute an operon. Their expression is induced both by osmotic stress and by growth into the stationary phase and depend on the sigma factor encoded by rpoS (katF). rpoS is amber-mutated in E. coli K-12 and its DNA sequence varies among K-12 strains. For trehalose catabolism under osmotic stress E. coli depends on the osmotically inducible periplasmic trehalase (TreA). In the absence of osmotic stress, trehalose induces the formation of an enzyme IITre (TreB) of the group translocation system, a catabolic trehalose-6-phosphate phosphatase (TreE), and an amylotrehalase (TreC) which converts trehalose to free glucose and a glucose polymer.
Invasion of murine intestinal M cells by Salmonella typhimurium inv mutants severely deficient for invasion of cultured cells (1996)

We have examined the role of the Salmonella typhimurium inv locus in invasion of the murine intestine. Previous studies have demonstrated that M cells within the lymphoid-follicle-associated epithelia are the primary site of intestinal invasion by S. typhimurium. In this study, we show that mutants possessing defects in one of two inv genes, invA or invG, which render them severely deficient for invasion of polarized epithelial MDCK cells, retain their ability to actively invade mouse Peyer's patch M cells. The interaction of these mutants with M cells was associated with apical membrane remodelling resembling that induced by wild-type strains. These data demonstrate that Salmonella invasion in vivo can proceed via mechanisms other than those previously defined in cultured cells.
Overexpression of fetal human pigment epithelium-derived factor in Escherichia coli. A functionally active neurotrophic factor. (1993)

Pigment epithelium-derived factor (PEDF) is a neurotrophic protein present in low amounts in conditioned medium of cultured fetal human retinal pigment epithelial cells. Recently, the PEDF cDNA has been cloned from a fetal human cDNA library, and its derived amino acid sequence identified it as a member of the serine protease inhibitor (serpin) supergene family (Steele, F. R., Chader, G. J., Johnson, L. V., and Tombran-Tink, J. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 1526-1530). We have prepared recombinant expression constructs from the fetal human PEDF cDNA and obtained milligram amounts of biologically active PEDF from Escherichia coli. The full-length open reading frame (Met1-Pro418) and a truncated form (Asp44-Pro418) were used in our constructs. Induction from a vector containing the truncated PEDF version, named pEV-BH, produced a protein (BH) of expected size (M(r) 42,800) associated with inclusion bodies, which contained 25-40% of expressed protein. After solubilization, BH was highly purified by gel filtration and cation exchange chromatography. The NH2-terminal sequence of the purified protein matched that of the pEV-BH construct. We have conducted neurite outgrowth assays in a human retinoblastoma Y-79 cell culture system. Recombinant PEDF (BH) demonstrated neurotrophic activity, as reported for the native PEDF. Thus, unfolded and refolded in vitro BH retained a potent biological activity. In parallel experiments, protease inhibition assays were performed. Recombinant PEDF did not have an effect on trypsin, chymotrypsin, elastase, cathepsin G, endoproteinase Lys-C, endoproteinase Glu-C, or subtilisin activity, suggesting that inhibition of known serine proteases is not the biochemical pathway for the PEDF neutrophic activity.
Solubilization and Microemulsification of Chlorinated Solvents Using Direct Food Additive (Edible) Surfactants (1994)

Abstract Surfactant enhanced subsurface remediation is being evaluated as an innovative technology to expedite contaminant extraction from the subsurface. Regulatory approval of this technology will likely be enhanced by use of surfactants with FDA direct food additive status (“edible” surfactants). This research establishes edible surfactant systems capable of solubilizing (via micellar partitioning) and microemulsifying (via middle phase microemulsions) chlorinated solvents (PCE, TCE, and trans 1,2‐DCE). Micellar partition coefficients with edible surfactants are observed to be comparable to values previously reported for other surfactants, with solubilization increasing aqueous concentrations by one to two orders of magnitude for the chlorinated organics. Middle phase microemulsion formation is dependent on surfactant structure and cosurfactant concentration. Solubility enhancement in the middle phase systems (microemulsification) is at least one to two orders of magnitude higher than solubilization for the same surfactant concentration, but is much more sensitive to the surfactant system and the contaminant. In addition, successful microemulsion formation is seen to be a function of ground‐water temperature and hardness, indicating the need to consider these and additional factors for successful design and implementation of surfactant enhanced subsurface remediation. This research thus establishes a variety of edible surfactant systems that can significantly expedite subsurface remediation of chlorinated solvents, and illustrates the importance of proper selection and design of surfactant systems.
FAA Pre-Emption: When Should Conflicting State Law Be Pre-Empted by the FAA - Weston Securities Corp. v. Aykanian (1999)

Since the creation of the F.A.A., courts, including the United States Supreme Court, have considered whether the F.A.A. pre-empts conflicting state law. Although courts generally find that the F.A.A. pre-empts state substantive and procedural law when it stands as an obstacle to Congress' goal of enforcing arbitration,5 the Massachusetts Court of Appeals, in Weston Securities Corp. v. Aykanian, made its own determination on this issue, since it was a case of first impression for the court. The court faced the question of whether a Massachusetts procedural rule, which did not allow an immediate appeal from an order to arbitrate, was pre-empted by the F.A.A. The court's holding expanded the federal policy favoring enforcement of arbitration agreements in Massachusetts by upholding a state procedural rule that promoted arbitration agreements by disallowing certain judicial appeals. The court, therefore, held that the rule was not pre-empted by the F.A.A., even though it contradicted the F.A.A.'s corresponding rule.
Mutations in the cueA gene encoding a copper homeostasis P-type ATPase reduce the pathogenicity of Pseudomonas aeruginosa in mice (2005)

A sequencing project identified a putative copper homeostasis gene, cueA, in Pseudomonas aeruginosa strain PAO1. Strains with mutations of the cueA gene, encoding a P-type ATPase linked to copper homeostasis in P. putida, displayed greater sensitivity to copper compared to wild-type bacteria using MIC determinations and in vitro passage in growth media with different concentrations of copper added. An LD50 assay showed a cueA deletion mutant was 50-fold more attenuated than wild-type strain PAO1 bacteria. Complementation of the cueA mutation restored in vitro tolerance to copper and virulence in a systemic model of infection to near wild-type levels. Competition assays between cueA mutants and wild-type P. aeruginosa strains demonstrated 20-fold attenuation by the cueA mutants within spleens of mice. This data suggests the P. aeruginosa CueA protein may be important in maintaining copper homeostasis both in vitro and in vivo.
a Long Sequence (1991)

We discuss a kinematic model based approach for the estimation of 3-D motion and structure parameters from a sequence of noisy monocular images. The approach is based on representing the constant velocity translation and constant angular velocity motion using nine rectilinear motion parameters, which are the 3D vectors of initial position, linear velocity, and angular velocity. The rotational motion is propagated in the kinematic model using the standard 3 x 3 rotation matrix. The measurements are noisy perturbations of two dimensional image locations of feature points. It is assumed that the 3-D feature points are extracted from the images and matched over the frames. The structure of the moving object is represented by the coordinates of feature points in a 3-D coordinate system fixed on the object. A nonlinear least squares method is used to formulate the batch estimation of motion and structure parameters. Owing to the nonlinearity in perspective projection, a conjugate gradient search method is used to obtain the estimates of motion and structure parameters. Occlusion is allowed among image frames. Images taken at nonuniform instances are also considered. Simulation results are included.
Cellular and molecular mechanics by atomic force microscopy: Capturing the exocytotic fusion pore  in vivo ? (1997)

The atomic force microscope (AFM) is a remarkably simple instrument that can measure forces down to piconewtons and can resolve force changes caused by the displacement of its probe by a fraction of a nanometer. Furthermore, these measurementscanbedoneunderwater,allowingforthestudy of biological material under conditions that resemble thosein vivo.TheAFMfunctionslikeaminiaturephonograph.Asharp tip,mountedonacantilever,interactswiththesample,causing minutedeflectionsthatcanbecalibratedasaforce.TheAFM, in its force-measuring mode, has been applied to the study of molecular mechanics. For example, the laboratory of Hermann Gaub in Munich succeeded in the remarkable feat of measuring the adhesion force between single avidin‐biotin pairs (’160 pN; ref. 1). These measurements were independently confirmed by molecular dynamic simulations of the avidin‐biotininteractionthatrevealedtheatomictrajectoryof a rupture and predicted the associated forces (2). Hence, the techniquesofmolecularmechanicsnowrivalthecapabilitiesof patch-clamp techniques (3) in describing the activity of single proteins. The patch-clamp technique seals a lipid membrane, containingionchannelproteins,ontoaglasspipetteelectrode. Ioniccurrentsflowingthroughasingleionchannelproteinare then easily measured, reporting on the conformational states of the transmembrane protein. In contrast to the patch-clamp technique, useful mainly for the characterization of ion channels, molecular mechanics studies can be done on single proteins or more complex structures that do not carry an associated electrical activity. ThemostfamiliaruseoftheAFMisincreatingtopographic imagesofasample.ThisisdonebyscanningtheAFMtipover the sample and recording the z axis displacement required to maintain a constant contact force. The nanometer resolution of the AFM imaging technique has been used to examine the structural features of proteins, producing data that is comparable to that obtained by x-ray crystallography (4). However, the biggest promise of the AFM technique is in the measurement of the activity of single protein structuresin vivoduring signaling events or during other types of cellular activities. Indeed, we may be getting close. A recent example demonstratedthatitispossibletoobserveconformationalchangesin the structure of a single nuclear pore in Xenopus oocyte nuclear envelopes (5). However, these measurements were doneinfixedtissue.RecentworkfromthelaboratoryofBhanu
Polymer hydrophilicity and hydrophobicity induced by femtosecond laser direct irradiation (2009)

Controlled modification of surface wettability of polymethyl methacrylate (PMMA) was achieved by irradiation of PMMA surface with femtosecond laser pulses at various laser fluences and focus distances. Fluences from 0.40 to 2.1 J/cm2 produced a hydrophobic surface and 2.1 to 52.7 J/cm2 (maximum investigated) produced a hydrophilic surface. Fluences less than 0.31 J/cm2 had no effect on the wettability of the raw PMMA. This change in wettability was caused dominantly by laser induced chemical structure modification and not by a change in surface roughness.
Isolation and characterization of human melanoma cell variants expressing high and low levels of CD44. (1991)

Variants of the human melanoma cell line LT5.1 were selected for high and low expression of the Mr 90,000 CD44 glycoprotein by using the Hermes-3 monoclonal antibody combined with fluorescence-activated cell sorting. Cells were single cell cloned and clones of CD44 high-expressing and CD44 low-expressing phenotype were isolated. The variants, which exhibited up to a 7-fold difference between high and low expression, have maintained a stable phenotype over a period of 3 months in tissue culture. Northern blot analysis of mRNA from the different clones showed correlation of levels of transcripts with fluorescence-activated cell sorting analysis data. Wound migration assays, utilizing the different clones, showed that the low-expressing clones manifested less motility than did cells showing high levels of CD44. Homotypic aggregation of cells was increased in those cells expressing high levels of CD44, and these variants were also better able to adhere to hyaluronate substrates. All of these activities were inhibited by the presence of anti-CD44 antibody. When injected i.v. into nu/nu BALB/c mice, the low-expressing clones gave significantly fewer lung nodules than the high-expressing clones, although the two variant types did not differ in their capacity to form s.c. tumors in similar mice. These results suggest that the CD44 molecule, possibly as a function of its activities as a hyaluronate receptor, may play a vital role in determining the fate of hematogenously disseminating melanoma cells.
HA receptors: Regulators of signalling to the cytoskeleton (1996)

Hyaluronan (HA) is a ubiquitous component of the extracellular matrix (ECM) and occurs transiently in both the cell nucleus and cytoplasm. It has been shown to promote cell motility, adhesion, and proliferation and thus it has an important role in such processes as morphogenesis, wound repair, inflammation, and metastasis. These processes require massive cell movement and tissue reorganization and are always accompanied by elevated levels of HA. Many of the effects of HA are mediated through cell surface receptors, three of which have been molecularly characterized, namely CD44, RHAMM, and ICAM-1. Binding of the HA ligand to its receptors triggers signal transduction events which, in concert with other ECM and cytoskeletal components, can direct cell trafficking during physiological and pathological events. The HA mediated signals are transmitted, at least in part, by the activation of protein phosphorylation cascades, cytokine release, and the stimulation of cell cycle proteins. A variety of extracellular signals regulate the expression of both HA and the receptors necessitating that HA-receptor signalling is a tightly controlled process. Regulated production of soluble forms of the receptors, alternately spliced cell surface isoforms, and glycosylation variants of these receptors can dramatically modulate HA binding, ligand specificity, and stimulation of the signalling pathway. When these processes are deregulated cell behaviour becomes uncontrolled leading to developmental abnormalities, abnormal physiological responses, and tumorigenesis. The elucidation of the molecular mechanisms regulating HA-mediated events will not only contribute greatly to our understanding of a variety of disease processes but will also offer many new avenues of therapeutic intervention.
Autonomic Dysfunction in Migraineurs (1999)

Subjects with migraine with aura had resting supine sympathetic hypofunction and intact parasympathetic function. With head-up tilt, sympathovagal balance is increased. The dynamic alterations in autonomic nervous system function may contribute to the development of aura in patients with migraine.
Effect of febuxostat on pharmacokinetics of desipramine, a CYP2D6 substrate, in healthy subjects (2005)

Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase (NP-SIXO) being developed for the management of hyperuricemia in patients with gout. Background In-vitro data showed that febuxostat had no significant effect on CYP1A2, CYP2C9, CYP2C19 or CYP3A4 activity (Ki>100 μM), and a weak inhibitory effect on CYP2D6 (Ki=40 μM). Aim The effect of febuxostat on desipramine pharmacokinetics (PK) was evaluated. Methods A phase-1, two-period, crossover, double-blind study was conducted in 18 CYP2D6 extensive-metabolizer subjects. Each subject received a single 25 mg oral dose of desipramine (DES) after multiple oral dosing with febuxostat (FBX) 120 mg or placebo (PLA) once daily. Blood samples were collected to assess the PK of DES and 2-hydroxydesipramine (2-HD). Results The results are shown in the table below. The increase in total exposure to DES and the concomitant decrease in the 2-HD/DES AUC ratio suggest that the metabolism of DES to 2-HD via CYP2D6 was mildly inhibited. However, this effect was not considered to be clinically significant. The incidence of adverse events was similar between treatment regimens with the majority being mild and moderate in severity. Conclusion No dose adjustment is expected for CYP2D6 substrates when co-administered with febuxostat. Clinical Pharmacology & Therapeutics (2005) 77, P43–P43; doi: 10.1016/j.clpt.2004.12.059 Table 1. Mean±SD Plasma PK for DES and 2-HD, Point Estimates (PE) and Confidence Intervals (CI) Parameter DES + FBX DES + PLA PE (90% CI)1 DES Cmax (ng/mL) 9.6 ± 3.5 8.4 ± 3.2 1.16 (1.10–1.23) AUC∞ (ng h/mL) 295 ± 194 263 ± 249 1.22 (1.11–1.35) 2-HD Cmax (ng/mL) 6.2 ± 2.0 6.6 ± 2.3 0.96 (0.90–1.02) AUC∞ (ng h/mL) 163 ± 30 166 ± 62 1.02 (0.93–1.11) AUC Ratio2 0.74 ± 0.40 0.88 ± 0.49 0.83 (0.76–0.91} 1 Ratio of DES+FBX to DES+PLA 2 AUC Ratio: 2-HD/DES AUC ratio
Relation of Intima-Media Thickness to Atherosclerotic Plaques in Carotid Arteries (1996)

This study examined the relation between arterial wall thickness and local atherosclerosis in the carotid arteries (CAs) and their specific risk factors. B-mode ultrasonography of the CAs was performed in a cohort of 516 men and 756 women aged 59 to 71 years who had been recruited for the European Vascular Aging Study. Ultrasound examination included measurement of intima-media thickness of the common CA (CCA) and the sites of plaque in the internal CA and bifurcations. Significant associations between increases in CCA intima-media thickness and both the presence and severity of atherosclerotic plaque were found in men and women. Examination of specific risk factors for increases in CCA intima-media thickness in the presence of plaque showed that, after adjustment for sex, both ultrasound measurements were independently related to age, body mass index, hypertension, and ever smoking (versus never smoking). Diabetes and current smoking were associated with intima-media thickness only, whereas hypercholesterolemia was related to plaque only. However, when subjects who were taking lipid-lowering drugs were excluded, lipoproteins and apolipoproteins were more consistently related to intima-media thickness than to plaque. In subjects free from any antihypertensive treatment, both intima-media thickness and plaques were independently associated with systolic blood pressure. After adjustment for sex and other risk factors, the odds ratio for having at least one plaque associated with a 0.10-mm increase in CCA intima-media thickness was 1.18 (95% confidence interval, 1.05 to 1.32). In this relatively aged population, increases in intima-media thickness as measured in the CCAs were clearly related to locally detected atherosclerosis and known risk factors for atherosclerosis. Longitudinal studies are needed to clarify the role of arterial wall thickening in the atherosclerotic process.
In vitro evaluation of novel antisense oligonucleotides is predictive of in vivo exon skipping activity for Duchenne muscular dystrophy (2010)

In vitro screening of different AOs within the same chemical class is a reliable method for predicting the in vivo exon skipping efficiency of AOs for DMD.
Pharmacogenetics of Antiangiogenic and Antineovascular Therapies of Age-Related Macular Degeneration (2012)

Age-related macular degeneration (AMD), the most common age-related disease causing irreversible visual loss in industrialized countries, is a complex and multifactorial illness. Researchers have found components of the complement alternative pathway inside drusen and Bruch's membrane of AMD patients, underlying a possible important role of complement factor H in the pathogenesis of AMD. The neovascular (wet) AMD is the most destructive form and it is characterized by invasion of new blood vessels into subretinal spaces with subsequent exudation and bleeding, resulting in scarring of the macular region and loss of the central vision. The hallmark of the neovascular form is the choroidal neovascularization, where VEGF-A has an important role in the pathogenesis of the disease. SNPs of these genes have recently been investigated as potential pharmacogenetic markers of the antiangiogenic and antineovascular therapy of AMD, which includes verteporfin photodynamic therapy and anti-VEGF-A drugs, such as pegaptanib, bevacizumab and ranibizumab. The CFH rs1061170 CT and TT genotypes have been associated with an improvement of visual acuity in bevacizumab or ranibizumab treated patients, whereas patients harboring VEGF-A rs699946 G allele responded better to bevacizumab-based therapy if compared with patients carrying the A allele. In conclusion, the discovery of pharmacogenetic markers for the personalization of the antiangiogenic and/or antineovascular therapy could be, in the future, a key issue in ophthalmology to obtain a personalization of the therapy and to avoid unnecessary costs and adverse drug reactions.