gebhart/patrepeval huggingface dataset:
Fibroblast Growth Factor 21 Prevents Atherosclerosis by Suppression of Hepatic Sterol Regulatory Element-Binding Protein-2 and Induction of Adiponectin in Mice (2015)

FGF21 protects against atherosclerosis via fine tuning the multiorgan crosstalk among liver, adipose tissue, and blood vessels.
Protective Effect of Dietary Supplementation with <i>L-</i>Arginine and <i>L-</i>Carnitine on Hypoxia/Reoxygenation-Induced Necrotizing Enterocolitis in Young Mice (2002)

Oxygen-derived free radicals are important components of gastrointestinal injury in necrotizing enterocolitis (NEC). In the present investigation, we examined the protective actions of L-arginine, a nitric oxide synthase substrate, and L-carnitine against hypoxia-reoxygenation (H/R) induced NEC in young mice. Young mice were divided into four groups: group 1 mice were subjected to H/R only; group 2 H/R mice were supplemented with L-arginine in the drinking water (2 g/l) for 7 days; group 3 H/R mice were given L-carnitine solution in water (50 mg/kg p.o.) for 7 days, and group 4 mice served as controls. Hypoxia was induced by placing the mice in a 100% CO(2) chamber for 5 min. After hypoxia, the mice were reoxygenated for 10 min with 100% oxygen. We examined the intestinal lesions by light microscopy and measured the intestinal generation of thiobarbituric acid reactive substances (TBARS) and the activities of superoxide dismutase and catalase in the H/R-induced model of NEC. In both L-arginine and L-carnitine groups, the NEC-induced intestinal tissue damage was greatly attenuated, with necrosis limited partially to the mucosa. The tissue TBARS level was significantly higher in group 1 than in any of the other groups (p < 0.001). However, those treated with L-arginine and L-carnitine had TBARS levels similar to those in the control animals. An increased tissue concentration of nitrate, a stable metabolite of nitric oxide, was found in the L-arginine-supplemented group as compared with the control group (p < 0.05). Both superoxide dismutase and catalase activities in the intestine were similar in H/R groups when compared with the intestine of control animals. The present study suggests that oxygen-derived free radicals are involved in the pathogenesis of H/R-induced NEC. This study also shows that dietary supplementation with L-arginine and L-carnitine ameliorates the histological evidence of H/R-induced intestinal injury and significantly decreases lipid peroxidation in H/R-induced bowel injury. Based on these findings, the beneficial effects of L-arginine and L-carnitine in this model may be mediated via mechanisms preventing free radical damage.
A2E, a Pigment of the Lipofuscin of Retinal Pigment Epithelial Cells, Is an Endogenous Ligand for Retinoic Acid Receptor (2008)

Lipofuscin contains fluorophores, which represent a biomarker for cellular aging. Although it remains unsubstantiated clinically, experimental results support that the accumulation of lipofuscin is related to an increased risk of choroidal neovascularization due to age-related macular degeneration, a leading cause of legal blindness. Here, we report that a major lipofuscin component, A2E, activates the retinoic acid receptor (RAR). In vitro experiments using luciferase reporter assay, competitional binding assay, analysis of target genes, and chromatin immunoprecipitation (ChIP) assay strongly suggest that A2E is a bona fide ligand for RAR and induces sustained activation of RAR target genes. A2E-induced vascular endothelial growth factor (VEGF) expression in a human retinal pigment epithelial cell line (ARPE-19) and RAR antagonist blocked the up-regulation of VEGF. The conditioned medium of A2E-treated ARPE-19 cells induced tube formation in human umbilical vascular endothelial cells, which was blocked by the RAR antagonist and anti-VEGF antibody. These results suggest that A2E accumulation results in the phenotypic alteration of retinal pigment epithelial cells, predisposing the environment to choroidal neovascularization development. This is mediated through the agonistic function of A2E, at least in part. The results of this study provide a novel potential therapeutic target for this incurable condition.
Detection of tumor stem cell markers in pancreatic carcinoma cell lines. (2007)

Two stem cell markers, ABCG2 and CD133 are expressed in pancreatic carcinoma cell lines. ABCG2 and/or CD133 positive cells may represent subpopulation of putative cancer stem cells also in this malignancy. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, they may be a very promising target for new drug developments.
In vitro characterization of an internal ribosomal entry site (IRES) present within the 5' nontranslated region of hepatitis A virus RNA: comparison with the IRES of encephalomyocarditis virus (1994)

The lengthy 5' nontranslated region (5'NTR) of hepatitis A virus (HAV) forms a highly ordered secondary structure, which has been suggested to play an important role in controlling viral translation by allowing for translation initiation by internal ribosome entry. To test this hypothesis, synthetic bicistronic RNAs, with all or part of the HAV 5'NTR in the intercistronic space, were translated in rabbit reticulocyte lysates. In the presence of an upstream cistron designed to block ribosomal scanning, the HAV 5'NTR was capable of directing the internal initiation of translation, confirming the presence of an internal ribosome entry site (IRES). Analysis of various deletion mutants demonstrated that the 5' border of the IRES is located between nucleotides 151 and 257, while the 3' border extends to the 3' end of the 5'NTR, between nucleotide 695 and the first initiation codon at 735. Except for a segment between bases 638 and 694, deletion of stem-loop structures between bases 151 and the 3' end of the 5'NTR inhibited or abolished translation. The addition of a 5' cap structure (m7GpppN) to monocistronic or bicistronic transcripts decreased the translation of a reporter gene downstream of the HAV 5'NTR but enhanced translation of the upstream cistron in bicistronic transcripts. This finding indicates that a 5' cap structure is inhibitory to HAV IRES-directed translation initiation and that the cap structure and the HAV IRES probably compete for the same limiting translation factors. The efficiency with which monocistronic constructs containing the HAV 5'NTR directed translation in reticulocyte lysates was compared with results for monocistronic constructs containing the IRES of the more rapidly growing encephalomyocarditis virus (EMCV). These results indicated that the HAV 5'NTR was more than 25-fold less active than the EMCV IRES in producing translation product. HAV 5'NTR-directed translation was inhibited by the presence of a one-fifth molar quantity of RNA containing the EMCV IRES, while a fivefold molar excess of the HAV 5'NTR did not inhibit EMCV IRES-directed translation. The relatively weak activity of the HAV IRES may thus be due to a reduced affinity for cellular translation factors which are present in limiting quantities in rabbit reticulocyte lysate.
Monolithic integration of RF-MEMS within CMOS (2015)

The evolution of mobile air interface standards continues to proliferate the modes and bands that must be supported in mobile devices. The mobile RF front-end has seen limited integration due to the diverse technologies required to meet the stringent performance requirements and poor scaling due to physical power and wavelength limitations. Programmable/tunable RF front-ends have been considered for many years but technologies providing sufficient performance at low cost were not available. We present a tunable RF product platform based on RF-MEMS integrated within CMOS that enables programmable front-ends and early products based on that platform.
The Yale-Brown Obsessive Compulsive Scale (1989)

The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessive-compulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's alpha coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.
The splicing regulatory element, UGCAUG, is phylogenetically and spatially conserved in introns that flank tissue-specific alternative exons (2005)

Previous studies have identified UGCAUG as an intron splicing enhancer that is frequently located adjacent to tissue-specific alternative exons in the human genome. Here, we show that UGCAUG is phylogenetically and spatially conserved in introns that flank brain-enriched alternative exons from fish to man. Analysis of sequence from the mouse, rat, dog, chicken and pufferfish genomes revealed a strongly statistically significant association of UGCAUG with the proximal intron region downstream of brain-enriched alternative exons. The number, position and sequence context of intronic UGCAUG elements were highly conserved among mammals and in chicken, but more divergent in fish. Control datasets, including constitutive exons and non-tissue-specific alternative exons, exhibited a much lower incidence of closely linked UGCAUG elements. We propose that the high sequence specificity of the UGCAUG element, and its unique association with tissue-specific alternative exons, mark it as a critical component of splicing switch mechanism(s) designed to activate a limited repertoire of splicing events in cell type-specific patterns. We further speculate that highly conserved UGCAUG-binding protein(s) related to the recently described Fox-1 splicing factor play a critical role in mediating this specificity.
Secretory Pathway of Trypanosomatid Parasites (2002)

The Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Trypanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles in the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory transport and protein glycosylation that may be exploited in developing new antiparasite drugs.
Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population (2001)

OBJECTIVE To report the mortality of left ventricular systolic dysfunction (LVD), assessed objectively by echocardiography, and its association with natriuretic peptide hormones in a random sample of 1640 men and women aged 25–74 years from a geographical, urban population. METHODS Left ventricular function was measured by echocardiography in 1640 attendees studied in 1992–3. LVD was defined as a left ventricular ejection fraction (LVEF) ⩽ 30%. Plasma concentrations of N-terminal atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP) were measured by standard radioimmunoassays. Mortality was documented at four years. RESULTS The four year all cause mortality rate in the whole cohort was 4.9% (80 deaths). It was 21% (nine deaths) in those with an LVEF ⩽ 30% and 4% in those whose LVEF was &gt; 30% (p &lt; 0.001). The median (interquartile range) BNP concentration in those who died was 16.9 pg/ml (8.8–27) and 7.8 pg/ml (3.4–13) in survivors (p &lt; 0.0001). Similarly, N-ANP had a median concentration of 2.35 ng/ml (1.32–3.36) in those with a fatal outcome and 1.27 ng/ml (0.9–2.0) in those alive at four years (p &lt; 0.0001). Subjects with an LVEF ⩽ 40% also had a significant mortality rate of 17% if they also had a BNP concentration ⩾ 17.9 pg/ml compared with 6.8% if their BNP was below this concentration (p = 0.013). Multivariate analysis revealed the independent predictors of four year all cause mortality to be increasing age (p &lt; 0.001), a BNP concentration ⩾ 17.9 pg/ml (p = 0.006), the presence of ischaemic heart disease (p = 0.03), and male sex (p = 0.04). CONCLUSIONS LVD is associated with a considerable mortality rate in this population. BNP also independently predicts outcome. In addition to its role as a diagnostic aid in chronic heart failure and LVD, it provides prognostic information and clarifies the meaning of a given degree of LVD.
The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes. (1999)

These results indicate that IL-1beta and TNF-alpha secreted by macrophages may promote, at least in part, angiogenesis in CNVMs by stimulating VEGF production in RPE cells.
The potential of nitric oxide releasing therapies as antimicrobial agents (2012)

Nitric oxide (NO) is a short-lived, diatomic, lipophilic gas that plays an integral role in defending against pathogens. Among its many functions are involvement in immune cell signaling and in the biochemical reactions by which immune cells defend against bacteria, fungi, viruses and parasites. NO signaling directs a broad spectrum of processes, including the differentiation, proliferation, and apoptosis of immune cells. When secreted by activated immune cells, NO diffuses across cellular membranes and exacts nitrosative and oxidative damage on invading pathogens. These observations led to the development of NO delivery systems that can harness the antimicrobial properties of this evanescent gas. The innate microbicidal properties of NO, as well as the antimicrobial activity of the various NO delivery systems, are reviewed.
Nicotinamide and dexamethasone inhibit interleukin-1-induced nitric oxide production by RINm5F cells without decreasing messenger ribonucleic acid expression for nitric oxide synthase (1993)

Nitric oxide (NO) generation may be a final common pathway for beta-cell damage in early insulin-dependent diabetes mellitus. Insulin-producing cells express an inducible form of NO synthase (iNOS), which is similar to that observed in activated macrophages. Induction of iNOS mRNA in these cells depends on protein synthesis. To further characterize the regulation of iNOS induction in insulin-producing cells, RINm5F cells (RIN cells) were exposed for 6 h to human recombinant interleukin-1 beta (rIL-1 beta; 1 ng/ml) alone or in combination with either nicotinamide (10, 20, or 50 mM) or dexamethasone (1 or 5 microM). These agents have been previously shown to prevent activation of iNOS in macrophages, fibroblasts, and hepatocytes. rIL-1 beta induced the expression of iNOS mRNA in RIN cells and a 12- to 13-fold increase in medium nitrite accumulation, the latter indicating NO production. Nicotinamide decreased nitrite production in a dose-dependent way. Thus, 10 mM nicotinamide decreased rIL-1 beta-induced nitrite formation by 30%, 20 mM by 60%, and 50 mM by 90%. The highest concentration of nicotinamide also prevented rIL-1 beta-induced iNOS mRNA, an effect associated with inhibition of total protein biosynthesis. However, 10 or 20 mM nicotinamide did not modify rIL-1 beta-induced iNOS mRNA expression or inhibit protein biosynthesis. Dexamethasone also decreased rIL-1 beta-induced nitrite production without affecting iNOS mRNA expression. As a whole, these data suggest that both nicotinamide and dexamethasone may prevent NO accumulation in insulin-producing cells by posttranscriptional mechanisms. It is also possible that these drugs induce direct inhibition of iNOS enzymatic activity and/or scavenge NO. Higher concentrations of nicotinamide might also inhibit iNOS mRNA expression, possibly by blocking protein biosynthesis.
Power of the prepupillary pseudophakos. (1972)

lens" designed by the author (Binkhorst, I 959, I 967a,b).
Quantitative Magnetic Particle Imaging Monitors the Transplantation, Biodistribution, and Clearance of Stem Cells In Vivo (2015)

Stem cell therapies have enormous potential for treating many debilitating diseases, including heart failure, stroke and traumatic brain injury. For maximal efficacy, these therapies require targeted cell delivery to specific tissues followed by successful cell engraftment. However, targeted delivery remains an open challenge. As one example, it is common for intravenous deliveries of mesenchymal stem cells (MSCs) to become entrapped in lung microvasculature instead of the target tissue. Hence, a robust, quantitative imaging method would be essential for developing efficacious cell therapies. Here we show that Magnetic Particle Imaging (MPI), a novel technique that directly images iron-oxide nanoparticle-tagged cells, can longitudinally monitor and quantify MSC administration in vivo. MPI offers near-ideal image contrast, depth penetration, and robustness; these properties make MPI both ultra-sensitive and linearly quantitative. Here, we imaged, for the first time, the dynamic trafficking of intravenous MSC administrations using MPI. Our results indicate that labeled MSC injections are immediately entrapped in lung tissue and then clear to the liver within one day, whereas standard iron oxide particle (Resovist) injections are immediately taken up by liver and spleen. Longitudinal MPI-CT imaging also indicated a clearance half-life of MSC iron oxide labels in the liver at 4.6 days. Finally, our ex vivo MPI biodistribution measurements of iron in liver, spleen, heart, and lungs after injection showed excellent agreement (R(2) = 0.943) with measurements from induction coupled plasma spectrometry. These results demonstrate that MPI offers strong utility for noninvasively imaging and quantifying the systemic distribution of cell therapies and other therapeutic agents.
The N-Terminal Sequence of Tyrosine Hydroxylase Is a Conformationally Versatile Motif That Binds 14-3-3 Proteins and Membranes (2013)

Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the synthesis of catecholamine neurotransmitters, and a reduction in TH activity is associated with several neurological diseases. Human TH is regulated, among other mechanisms, by Ser19-phosphorylation-dependent interaction with 14-3-3 proteins. The N-terminal sequence (residues 1-43), which corresponds to an extension to the TH regulatory domain, also interacts with negatively charged membranes. By using X-ray crystallography together with molecular dynamics simulations and structural bioinformatics analysis, we have probed the conformations of the Ser19-phosphorylated N-terminal peptide [THp-(1-43)] bound to 14-3-3γ, free in solution and bound to a phospholipid bilayer, and of the unphosphorylated peptide TH-(1-43) both free and bilayer bound. As seen in the crystal structure of THp-(1-43) complexed with 14-3-3γ, the region surrounding pSer19 adopts an extended conformation in the bound state, whereas THp-(1-43) adopts a bent conformation when free in solution, with higher content of secondary structure and higher number of internal hydrogen bonds. TH-(1-43) in solution presents the highest mobility and least defined structure of all forms studied, and it shows an energetically more favorable interaction with membranes relative to THp-(1-43). Cationic residues, notably Arg15 and Arg16, which are the recognition sites of the kinases phosphorylating at Ser19, are also contributing to the interaction with the membrane. Our results reveal the structural flexibility of this region of TH, in accordance with the functional versatility and conformational adaptation to different partners. Furthermore, this structural information has potential relevance for the development of therapeutics for neurodegenerative disorders, through modulation of TH-partner interactions.
<title>Multiscale approach to mutual information matching</title> (1998)

Methods based on mutual information have shown promising results for matching of multimodal brain images. This paper discusses a multiscale approach to mutual information matching, aiming for an acceleration of the matching process while considering the accuracy and robustness of the method. Scaling of the images is done by equidistant sampling. Rigid matching of 3D magnetic resonance and computed tomography brain images is performed on datasets of varying resolution and quality. The experiments show that a multiscale approach to mutual information matching is an appropriate method for images of high resolution and quality. For such images an acceleration up to a factor of around 3 can be achieved. For images of poorer quality caution is advised with respect to the multiscale method, since the optimization method used (Powell) was shown to be highly sensitive to the local optima occurring in these cases. When incorrect intermediate results are avoided, an acceleration up to a factor of around 2 can be achieved for images of lower resolution. ©2003 Copyright SPIE - The International Society for Optical Engineering.
Evolution of amyloid: What normal protein folding may tell us about fibrillogenesis and disease (1999)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock (2008)

Low-dose vasopressin did not reduce mortality rates as compared with norepinephrine among patients with septic shock who were treated with catecholamine vasopressors. (Current Controlled Trials number, ISRCTN94845869 [controlled-trials.com].).
Searching Distributed Collections With Inference Networks (2017)

The use of information retrieval systems in networked environments raises a new set of issues that have received little attention. These issues include ranking document collections for relevance to a query, selecting the best set of collections from a ranked list, and merging the document rankings that are returned from a set of collections. This paper describes methods of addressing each issue in the inference network model, discusses their implementation in the INQUERY system, and presents experimental results demonstrating their effectiveness.