gebhart/patrepeval huggingface dataset:
Blocking Angiogenesis and Tumorigenesis with GFA-116, a Synthetic Molecule that Inhibits Binding of Vascular Endothelial Growth Factor to its Receptor (2004)

A small synthetic library of cyclohexapeptidomimetic calixarenes was prepared to identify disrupters of vascular endothelial growth factor (VEGF) binding to its receptor that inhibits angiogenesis. From this library, we discovered GFA-116, which potently inhibits (125)I-VEGF binding to Flk-1 in Flk-1-overexpressing NIH 3T3 cells and human prostate tumor cells with an IC(50) of 750 nM. This inhibition is highly selective for VEGF in that (125)I- platelet-derived growth factor binding to its receptor is not affected. GFA-116 inhibits VEGF-stimulated Flk-1 tyrosine phosphorylation and subsequent activation of Erk1/2 mitogen-activated protein kinases. Furthermore, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor-dependent stimulation of Erk1/2 phosphorylation are not affected at concentrations as high as 10 microM. In vitro, GFA-116 inhibits angiogenesis as measured by inhibition of migration and formation of capillary-like structures by human endothelial cells as well as suppression of microvessel outgrowth in rat aortic rings and rat cornea angiogenesis. In vivo, GFA-116 (50 mpk/day) inhibits tumor growth and angiogenesis as measured by CD31 staining of A-549 human lung tumors in nude mice. Furthermore, GFA-116 is also effective at inhibiting tumor growth and metastasis to the lung of B16-F10 melanoma cells injected into immunocompetent mice. Taken together, these results demonstrate that a synthetic molecule capable of disrupting the binding of VEGF to its receptor selectively inhibits VEGF-dependent signaling and suppresses angiogenesis and tumorigenesis.
A new regulator of the cell cycle (2011)

The ability of eukaryotes to alter chromatin structure and function is modulated, in part, by histone-modifying enzymes and the post-translational modifications they create. One of these enzymes, PR-Set7/Set8/KMT5a, is the sole histone methyltransferase responsible for the monomethylation of histone H4 lysine 20 (H4K20me1) in higher eukaryotes. Both PR-Set7 and H4K20me1 were previously found to be tightly cell cycle regulated suggesting that they play an important, although unknown, role in cell cycle progression. Several recent reports reveal that PR-Set7 abundance is dynamically regulated during different cell cycle phases by distinct enzymes including cdk1/cyclinB, Cdc14, SCF(Skp2), CRL4(cdt2) and APC(cdh1). Importantly, these reports demonstrate that inappropriate levels of PR-Set7 result in profound cell cycle defects including the inability to initiate S phase, the re-replication of DNA and the improper timing of mitotic progression. Here, we summarize the significance of these new findings, raise some important questions that require further investigation and explore several possibilities of how PR-Set7 and methylated H4K20 may likely function as novel regulators of the cell cycle.
Prospects for a hepcidin mimic to treat β-thalassemia and hemochromatosis (2011)

Keywords:: anemiaβ-thalassemiahemochromatosishepcidinineffective erythropoiesisiron overloadsplenomegaly
The effect of matrix on the binding of albumin to immobilized Cibacron Blue (1977)

With Cibacron Blue as a ligand, the suitability of Sepharose, Sephacryl, cellulose and Ultrogel as column supports for the affinity chromatography of human serum albumin was examined. Sepharose and Sephacryl were the most effective matrices. Albumin was readily removed from such columns by using an electrophoretic desorption technique.
Prostacyclin and Atherosclerosis — Experimental and Clinical Approach (1983)

Prostacyclin (PGI2) stimulates platelet adenylate cyclase, increases c-AMP levels in platelets and, therefore, inhibits release reaction, suppresses platelet aggregation and dissipates white platelet thrombi.
Paper spray ionization of polar analytes using non-polar solvents (2011)

Non-polar solvents like hexane allow ionization of insoluble drugs, peptides, nucleotides and phospholipids as solids from paper. Ambient ionization is achieved simply by application of a high voltage to the wet paper. Transport and ionization mechanisms are discussed, including the possibility of field desorption from dendritic structures formed on the paper.
Jagged-1 is required for the expansion of CD4+ CD25+ FoxP3+ regulatory T cells and tolerogenic dendritic cells by murine mesenchymal stromal cells (2015)

The current study suggests that MSC-mediated immune modulation involves the education and expansion of regulatory immune cells in a Jagged-1 dependent manner and provides the first report of the importance of Jagged-1 signalling in MSC protection against inflammation in vivo.
CD40/CD40 ligand interactions in immune responses and pulmonary immunity. (2011)

The CD40 ligand/CD40 pathway is widely recognized for its prominent role in immune regulation and homeostasis. CD40, a member of the tumor necrosis factor receptor family, is expressed by antigen-presenting cells, as well as non-immune cells and tumors. The engagement of the CD40 and CD40 ligands, which are transiently expressed on T cells and other non-immune cells under inflammatory conditions, regulates a wide spectrum of molecular and cellular processes, including the initiation and progression of cellular and humoral adaptive immunity. Based on recent research findings, the engagement of the CD40 with a deregulated amount of CD40 ligand has been implicated in a number of inflammatory diseases. We will discuss the involvement of the CD40 ligand/CD40 interaction in the pathophysiology of inflammatory diseases, including autoimmune diseases, atherothrombosis, cancer, and respiratory diseases.
Mimicking the nanofeatures of bone increases bone-forming cell adhesion and proliferation (2005)

There is a great need to design better orthopaedic implant devices by modifying their surface properties. In this respect, one approach that has received much attention of late is the simulation of the surface roughness of bone in synthetic orthopaedic implant materials. Bone has numerous nanometre features due to the presence of nanostructured entities such as collagen and hydroxyapatite. Despite this fact, current orthopaedic implant materials are smooth at the nanoscale. Previous studies have measured increased osteoblast (bone-forming cell) functions on biologically inspired nanophase titania compared to conventional titania formulations. In fact, in vitro calcium deposition by osteoblasts was up to three times higher on nanostructured compared to conventional titania. However, it was unclear in those studies what underlying surface properties (roughness, crystallinity, crystal phase, chemistry, etc) promoted enhanced functions of osteoblasts on nanophase titania. For that reason, the objective of the present in vitro study was to specifically determine the role nanostructured surface roughness of titania had on increasing functions of osteoblasts. To achieve this, the surface roughness of nanophase and conventional titania was transferred to a model tissue engineering polymer: poly-lactic-co-glycolic acid (PLGA). Results of the present study demonstrated greater osteoblast adhesion and proliferation for up to 5 days of culture on PLGA moulds of nanophase compared to conventional titania. In this manner, this study elucidated that the property of nanophase titania which increased osteoblast function was a large degree of nanometre surface features that mimicked bone. For this reason, nanophase materials deserve more attention in improving orthopaedic implant applications.
Plasma Adiponectin Concentrations in Relation to Endometrial Cancer: A Case-Control Study in Greece (2003)

Adiponectin is a hormone secreted exclusively by adipocytes, and obesity is an established risk factor for endometrial cancer. We have, thus, evaluated the association of adiponectin with the occurrence of endometrial cancer. Questionnaire information and blood samples were taken before treatment from 84 women with newly diagnosed, histologically confirmed endometrial cancer and 84 control women who were admitted for minor gynecologic problems, mainly pelvic prolapse. Adiponectin levels were measured by immunoassay. The results were analyzed through multiple logistic regression and controlled for known risk factors for endometrial cancer, leptin, as well as major components of the IGF system (IGF-I, IGF-II, and IGF-binding protein 3). Among control women, there was no significant association of adiponectin with age or parity. Although there was no association of adiponectin with endometrial cancer among women 65 yr or older, there was an inverse, fairly strong, and statistically significant inverse association among younger women. Among women younger than 65 yr, an increase of adiponectin by 1 SD was associated with a more than 50% reduction of the risk for endometrial cancer [odds ratio (OR) 0.44; 95% confidence interval (CI) 0.24-0.81], even after controlling for body mass index and other potential confounders. Among all women, the adjusted OR for a 1 SD increase in adiponectin was not significant (OR, 0.78; 95% CI, 0.56-1.10) but was significant for a one quintile increase in adiponectin (OR, 0.74; 95% CI, 0.56-0.97). In women younger than 65 yr, among whom obesity represents a powerful risk factor for endometrial cancer, adiponectin is inversely and significantly related to the risk of this disease. This association is independent of possible effects of major components of the IGF system, leptin, body mass index, sociodemographic variables, and known endometrial cancer risk factors. Future studies are needed to prove causality and provide insight on both the mechanism of action of this hormone and its potential role in endometrial cancer.
Extending the Stalk Enhances Immunogenicity of the Influenza Virus Neuraminidase (2019)

Influenza viruses express two surface glycoproteins, the hemagglutinin (HA) and the neuraminidase (NA). Anti-NA antibodies protect from lethal influenza virus challenge in the mouse model and correlate inversely with virus shedding and symptoms in humans. Consequently, the NA is a promising target for influenza virus vaccine design. Current seasonal vaccines, however, poorly induce anti-NA antibodies, partly because of the immunodominance of the HA over the NA when the two glycoproteins are closely associated. To address this issue, here we investigated whether extending the stalk domain of the NA could render it more immunogenic on virus particles. Two recombinant influenza viruses based on the H1N1 strain A/Puerto Rico/8/1934 (PR8) were rescued with NA stalk domains extended by 15 or 30 amino acids. Formalin-inactivated viruses expressing wild-type NA or the stalk-extended NA variants were used to vaccinate mice. The virus with the 30-amino-acid stalk extension induced significantly higher anti-NA IgG responses (characterized by increased <i>in vitro</i> antibody-dependent cellular cytotoxicity [ADCC] activity) than the wild-type PR8 virus, while anti-HA IgG levels were unaffected. Similarly, extending the stalk domain of the NA of a recent H3N2 virus enhanced the induction of anti-NA IgGs in mice. On the basis of these results, we hypothesize that the subdominance of the NA can be modulated if the protein is modified such that its height surpasses that of the HA on the viral membrane. Extending the stalk domain of NA may help to enhance its immunogenicity in influenza virus vaccines without compromising antibody responses to HA.<b>IMPORTANCE</b> The efficacy of influenza virus vaccines could be improved by enhancing the immunogenicity of the NA protein. One of the reasons for its poor immunogenicity is the immunodominance of the HA over the NA in many seasonal influenza virus vaccines. Here we demonstrate that, in the mouse model, extending the stalk domain of the NA protein can enhance its immunogenicity on virus particles and overcome the immunodominance of the HA without affecting antibody responses to the HA. The antibody repertoire is broadened by the extended NA and includes additional ADCC-active antibodies. Our findings may assist in the efforts toward more effective influenza virus vaccines.
Apolipoprotein B100 Metabolism in Autosomal-Dominant Hypercholesterolemia Related to Mutations inPCSK9 (2004)

These results showed that the effect of the S127R mutation of PCSK9 on plasma cholesterol homeostasis is mainly related to an overproduction of apolipoprotein B100.
The L-4F mimetic peptide prevents insulin resistance through increased levels of HO-1, pAMPK, and pAKT in obese mice (2009)

We examined mechanisms by which L-4F reduces obesity and diabetes in obese (ob) diabetic mice. We hypothesized that L-4F reduces adiposity via increased pAMPK, pAKT, HO-1, and increased insulin receptor phosphorylation in ob mice. Obese and lean mice were divided into five groups: lean, lean-L-4F-treated, ob, ob-L-4F-treated, and ob-L-4F-LY294002. Food intake, insulin, glucose adipocyte stem cells, pAMPK, pAKT, CB1, and insulin receptor phosphorylation were determined. Subcutaneous (SAT) and visceral adipose tissue (VAT) were determined by MRI and hepatic lipid content by magnetic resonance spectroscopy. SAT and VAT volumes decreased in ob-L-4F-treated animals compared with control. L-4F treatment decreased hepatic lipid content and increased the numbers of small adipocytes (P < 0.05) and phosphorylation of insulin receptors. L-4F decreased CB1 in SAT and VAT and increased pAKT and pAMPK in endothelium. L-4F-mediated improvement in endothelium was prevented by LY294002. Inhibition of pAKT and pAMPK by LY294002 was associated with an increase in glucose levels. Upregulation of HO-1 by L-4F produced adipose remodeling and increased the number of small differentiated adipocytes. The anti-obesity effects of L-4F are manifested by a decrease in visceral fat content with reciprocal increases in adiponectin, pAMPK, pAKT, and phosphorylation of insulin receptors with improved insulin sensitivity.
Longitudinal assessment of multiplex patient-specific ctDNA biomarkers in bladder cancer for diagnosis, surveillance and recurrence (2018)

Background: The use of circulating tumor DNA (ctDNA) as a biomarker for disease staging at diagnosis (DX), treatment response, and recurrence monitoring is an emerging field in many cancer types. In bladder cancer, the utility of ctDNA has shown promising results. Here we present a highly sensitive and specific NGS-based approach to ctDNA monitoring. Methods: A cohort of 50 patients with locally advanced muscle-invasive bladder cancer treated with neoadjuvant chemotherapy were included prospectively. For each patient, a panel of 16 tumor-specific mutations was designed (SignateraTM RUO) based on whole-exome sequencing of tumor and germline DNA. In total, we analyzed ctDNA from longitudinally collected plasma samples from 386 time points procured at diagnosis, during treatment, at cystectomy (Cx), and during monitoring until disease recurrence or up to 2 years follow-up. Results of ctDNA analyses were compared to radiographic imaging and clinical outcomes. ctDNA from longitudinally-collected urine samples will also be analyzed for treatment response and disease recurrence. Results: At DX, plasma ctDNA status was strongly prognostic of recurrence-free survival. Specifically, 62% (8/13) of the ctDNA+ patients at DX recurred after neoadjuvant treatment and Cx; conversely, none (0/22) of the ctDNA- patients recurred (log-rank; p < 0.0001). In addition, a strong correlation was also observed between presence of ctDNA after CX and disease relapse. Specifically, relapse after Cx was detected in 100% (10/10) of ctDNA+ patients ∼120 days (0–245 days) prior to radiographic imaging, while 0% (0/38) of ctDNA- patients relapsed (log-rank; p < 0.0001). Conclusions: We demonstrate a strong prognostic potential of ctDNA in bladder cancer at time of DX, suggesting a potential role for ctDNA in the staging of bladder cancer. Furthermore, we show ctDNA is detected in all patients with disease recurrence after Cx. Incorporation of ctDNA analysis into routine follow-up for early detection of relapse may allow earlier initiation of alternate treatment modalities. Legal entity responsible for the study: The National Committee on Health Research Ethics (#1302183), Denmark. Funding: Novo Nordisk Foundation, Danish Cancer Society, Natera Inc San Carlos USA. Disclosure: H. Sethi, S. Sharma, H-T. Wu, R. Swenerton, R. Salari, D. Hafez, R. Srinivasan, M. Balcioglu, S. Navarro, Z. Assaf, B. Zimmermann, J. Lin: Employee, stockownership or options to stock: Natera, Inc. All other authors have declared no conflicts of interest.
Derivatization in LC/MS (1998)

LC/MS is now considered to be the most promising analytical method for the determination of biological substances, especially nonvolatile or high molecular weight substances. But one of the drawbacks of this method is its low sensitivity in comparison with GC/MS. In order to overcome this problem, the derivatization methods are used in LC/MS. This report overviews the detection-oriented derivatization methods in LC/MS including our results. The typical examples are as follows. The derivatization of vitamin D with a Cookson-type reagent (analog of 4-phenyl-1, 2, 4-triazoline-3, 5-dione) gave satisfactory sensitivity, which was also observed on the derivatization of oxosteroids with O-methylhydroxylamine. Although the oxosteroid fatty acid esters gave a de-esterified ion as a base peak in atmospheric pressure chemical-ionization MS, the methyloxime of which gave a quasimolecular ion as a base peak, which is helpful to identify the compounds in the brain.
Inhibition of Hepadnavirus Reverse Transcriptase-ε RNA Interaction by Porphyrin Compounds (2007)

The hepatitis B virus (HBV) reverse transcriptase (RT) plays a multitude of fundamental roles in the viral life cycle and is the key target in the development of anti-HBV chemotherapy. We report here that the endogenous small molecule iron protoporphyrin IX (hemin) and several related porphyrin compounds potently blocked a critical RT interaction with the viral RNA packaging signal/origin of replication, called epsilon. As RT-epsilon interaction is essential for the initiation of viral reverse transcription, which is primed by RT itself (protein priming), the porphyrin compounds dramatically suppressed the protein-priming reaction. Further studies demonstrated that these compounds could target the unique N-terminal domain of the RT protein, the so-called terminal protein. Hemin and related porphyrin compounds thus represent a novel class of agents that can block HBV RT functions through a mechanism and target that are completely distinct from those of existing anti-HBV drugs.
CHARMS (2002)

Finite element solvers are a basic component of simulation applications; they are common in computer graphics, engineering, and medical simulations. Although adaptive solvers can be of great value in reducing the often high computational cost of simulations they are not employed broadly. Indeed, building adaptive solvers can be a daunting task especially for 3D finite elements. In this paper we are introducing a new approach to produce conforming, hierarchical, adaptive refinement methods (CHARMS). The basic principle of our approach is to refine basis functions, not elements. This removes a number of implementation headaches associated with other approaches and is a general technique independent of domain dimension (here 2D and 3D), element type (e.g., triangle, quad, tetrahedron, hexahedron), and basis function order (piece-wise linear, higher order B-splines, Loop subdivision, etc.). The (un-)refinement algorithms are simple and require little in terms of data structure support. We demonstrate the versatility of our new approach through 2D and 3D examples, including medical applications and thin-shell animations.
Interface exploration for reduced power in core-based systems (1998)

Reducing power dissipation is becoming more important in the design of embedded systems. Core-based system design opens up the opportunity for exploring different bus interfaces in order to optimize for reduced power. We give a first approach for exploring a range of possible bus configurations, such as width and coding schemes, for a given set of communication channels. Our approach uses power estimation formulas, for fast performance. We use this approach to explore different bus interfaces for a real GPS navigation system in order to select the optimal bus interface for minimum power consumption.
Optical biomolecular sensor based on surface plasmon resonance (1999)

A new optical bio-molecular sensors was developed for bio- molecular sensing based on light-excited surface plasmon resonance. Thickness of bio-molecule films absorbed onto a gold film is measured by the resonance condition of the surface plasmon on the sensing mental surface. The resonance condition is given by thickness of bio-molecule films faced on the mental. The developed sensor can be compact and simple, because of the absence of mechanical moving parts, by using a wedge of laser beam to obtain incident angle scanning and multi-channel angular light intensity detection with a charge coupled device. The sensor using Kretschmann configuration includes three parts: an optical measuring unit, a power source of laser, and a microcomputer used as data collection and handling. The adsorption of ferritin from phosphate buffered saline onto a gold film has been examined using the sensor. Application of the sensor allows elucidation of the surface layer thickness of dry ferritin on gold. Experiment results suggest less than monolayer coverage of ferritin on gold.
Clinical and Pharmacologic Study of Orally Administrated Uridine (1991)

Effects of oral administrations of uridine were investigated in a study of six healthy volunteer control subjects and nine patients with metastatic colorectal cancer. Oral uridine was studied as single-dose administrations at doses escalating from 0.3 to 12 g/m2 and as multiple-dose administrations every 6 hours for 3 days at doses from 5 to 10 g/m2. The maximum tolerated dose (MTD) was 10 to 12 g/m2 for a single dose of uridine and 5 g/m2 for the multiple-dose regimen. Diarrhea was the dose-limiting toxic effect. Single-dose oral uridine resulted in an increase in plasma uridine concentrations in the range of 60 to 80 microM after doses of 8 to 12 g/m2. At these doses, bioavailability of oral uridine ranged from 5.8% to 9.9%. At the MTD of 5 g/m2 in the multiple-dose uridine schedule, steady-state plasma uridine levels of approximately 50 microM were achieved. Further studies should explore the role of oral uridine in the modulation of the toxicity of fluorouracil.
Sickle cell disease and stroke (2009)

Twenty-four percent of sickle cell disease (SCD) patients have a stroke by the age of 45 years. Blood transfusions decrease stroke risk in patients deemed high risk by transcranial Doppler. However, transcranial Doppler has poor specificity, and transfusions are limited by alloimmunization and iron overload. Transfusion withdrawal may be associated with an increased rebound stroke risk. Extended blood typing decreases alloimmunization in SCD but is not universally adopted. Transfusions for thalassemia begun in early childhood are associated with lower rates of alloimmunization than are seen in SCD, suggesting immune tolerance. Optimal oxygen transport efficiency occurs at a relatively low hematocrit for SCD patients because of hyperviscosity. Consequently, exchange rather than simple transfusions are more effective in improving oxygen transport efficiency, but the former are technically more demanding and require more blood units. Although viscosity is of importance in the noncerebral manifestations of SCD, inflammation may play a larger role than viscosity in the development of large-vessel stroke. The future of SCD stroke management lies in the avoidance of transfusion. Hydroxyurea and anti-inflammatory measures may reduce the need for transfusion. Recent genome-wide association studies may provide methods for modulating fetal hemoglobin production enough to attenuate stroke risk and other complications of SCD.