gebhart/patrepeval huggingface dataset:
VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma. (2002)

Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is the most potent growth factor of tumor neovasculature, has been shown to be up-regulated in every tumor studied thus far, and is correlated with tumor stage and progression. To determine whether specific VEGF splice variants were differentially expressed in renal cell carcinomas, 18 polar tumor samples were analyzed by reverse transcription-PCR using primers designed to differentiate between VEGF splice variants. Control tissue was derived from the opposite normal pole. An amplicon of length consistent with the previously described variant VEGF(148) was found in normal kidney tissue. Subsequent sequencing revealed a new VEGF isoform formed by differential splicing from the end of exon 7 into the 3' untranslated region of the mRNA. Cloning of this transcript showed that translation would result in a 165-amino acid peptide with an alternative terminal 6 amino acids, followed by a stop codon. We have termed this new isoform VEGF165b. This isoform was present in 17 of 18 normal kidney samples but only 4 of 18 cases from matched malignant tissue. VEGF165b was therefore expressed in a significantly higher proportion of normal tissue than malignant tissue from the same patients (P < 0.001). To determine the functional significance of this new isoform, we expressed the full-length protein in a heterologous expression system. Conditioned medium containing this isoform significantly and dose dependently inhibited VEGF165-mediated proliferation, migration of endothelial cells, and vasodilatation of mesenteric arteries. This novel isoform VEGF165b is therefore an endogenous inhibitory form of VEGF that is down-regulated in renal tumors and, therefore, may be anti-angiogenesis.
Functional analysis of the Candida albicans ALS1 gene product (2004)

ALS1 encodes a cell surface protein that mediates adherence of Candida albicans to endothelial cells. The predicted Als1p has an N-terminal region, which contains a signal peptide; a middle region, which contains 20 36-amino acid tandem repeats; and a C-terminal region, which contains a glycosylphosphotidylinositol-anchorage sequence. We used site-directed mutagenesis to delineate the regions in Als1p required for endothelial cell adherence and cell surface expression of the protein. Mutant alleles of ALS1 containing either deletions or insertions were expressed in the normally non-adherent Saccharomyces cerevisiae. These transformants were analysed for endothelial cell adherence and cell surface expression of Als1p. We found that mutations centred around amino acid 285 in the N-terminus completely abolished adherence, but had no effect on cell surface expression of Als1p. Deletion of 15 of the tandem repeats reduced adherence by 50%, whereas deletion of all abolished adherence completely, even though cell surface expression of the N-terminus of Als1p was maintained. Insertions into the C-terminus at amino acids 413 and 254 upstream of the stop codon resulted in a modest loss of adherence, while cell surface expression of Als1p was maintained. An insertion at amino acid 249 in the C-terminus caused complete loss of both adherence and cell surface expression, even though the glycosylphosphotidylinositol-anchorage sequence remained intact. These data suggest a model of Als1p in which the endothelial cell binding region is localized within its N-terminus, the tandem repeats are essential for the proper presentation of the binding site, and the C-terminus is required for localizing Als1p to the cell surface.
Novel mutations of thePCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia (2005)

Autosomal dominant hypercholesterolemia (ADH) is a frequent (1/500) monogenic inherited disorder characterized by isolated elevation of LDL leading to premature cardiovascular disease. ADH is known to result from mutations at two main loci: LDLR (encoding the low density lipoprotein receptor), and APOB (encoding apolipoprotein B100), its natural ligand. We previously demonstrated that ADH is also caused by mutations of the PCSK9 (proprotein convertase subtilisin/kexin type 9) gene that encodes Narc-1 (neural apoptosis-regulated convertase 1). However, the role of this novel disease locus as a cause of hypercholesterolemia remains unclear. In the present study, we analysed the PCSK9 coding region and intronic junctions in 130 adult or pediatric patients with ADH, previously found as being non LDLR/non APOB mutation carriers. Four novel heterozygous missense variations were found: c.654A>T (p.R218S), c.1070G>A (p.R357H), c.1405C>T (p.R469W), and c.1327G>A (p.A443T). All mutations were absent in 340 normolipidemic controls. Except for the A443T, all mutations are nonconservative and modify a highly conserved residue. Segregation with hypercholesterolemia is incomplete in one pedigree. Type and severity of hyperlipidemia and of cardiovascular disease could vary among subjects from the same family. Finally, the proband carrying the R357H mutation exhibited very high plasma cholesterol during pregnancy, whereas the proband carrying the p.R469W mutation exhibited a severe phenotype of hypercholesterolemia in combination with a LDLR mutation resulting from a frameshift at residue F382 (1209delC). These observations suggest that variations in PCSK9 are a rare cause of non LDLR/non APOB ADH (approximately 2.3%) and that additional environmental or genetic factors may contribute to the phenotype caused by PCSK9 missense mutations in humans.
PRRSV, the virus (2000)

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-strand RNA virus that belongs to the Arteriviridae family. PRRSV grows in primary alveolar macrophages and in monkey kidney cell lines. The genomic RNA is approximately 15 kb. The genome encodes the RNA replicase (ORF1a and ORF1b), the glycoproteins GP2 to GP5, the integral membrane protein M, and the nucleocapsid protein N (ORFs 2 to 7). A comparison of nucleotide sequences of different strains indicates that European and North American strains represent two distinct antigenic types. Various PRRSV-specific monoclonal antibodies and recombinant structural proteins have been produced. Well-defined PRRSV mutants can be generated with the recently developed infectious cDNA clone of PRRSV.
Biofilms and Device-Associated Infections (2001)

Microorganisms commonly attach to living and nonliving surfaces, including those of indwelling medical devices, and form biofilms made up of extracellular polymers. In this state, microorganisms are highly resistant to antimicrobial treatment and are tenaciously bound to the surface. To better understand and control biofilms on indwelling medical devices, researchers should develop reliable sampling and measurement techniques, investigate the role of biofilms in antimicrobial drug resistance, and establish the link between biofilm contamination and patient infection.
Photonic Crystal Using Anodic Porous Alumina (1999)

Two-dimensional (2D) photonic crystals in the visible wavelength region were fabricated using anodic porous alumina with a highly ordered hole array configuration. The transmission properties of an ordered triangular array of an air cylinders with high aspect ratio in alumina matrix showed a stop band in the spectrum which corresponds to the band gap in the 2D photonic crystals.
A platelet biomarker for assessing phosphoinositide 3-kinase inhibition during cancer chemotherapy (2007)

Thrombin cleavages of selective proteinase-activated receptors (PAR) as well as PAR-activating peptide ligands can initiate the phosphoinositide 3-kinase (PI3K) signaling cascade in platelets. Downstream to this event, fibrinogen receptors on platelets undergo conformational changes that enhance fibrinogen binding. In our study, we used this phenomenon as a surrogate biomarker for assessing effects on PI3K activity. Our method, using flow cytometric measurement of fluorescent ligand and antibody binding, uncovered a 16- to 45-fold signal window after PAR-induced platelet activation. Pretreatment (in vitro) with the PI3K inhibitors wortmannin and LY294002 resulted in concentration-dependent inhibition at predicted potencies. In addition, platelets taken from mice treated with wortmannin were blocked from PAR-induced ex vivo activation concomitantly with a decrease in phosphorylation of AKT from excised tumor xenografts. This surrogate biomarker assay was successfully tested (in vitro) on blood specimens received from volunteer cancer patients. Our results indicate that measurement of platelet activation could serve as an effective drug activity biomarker during clinical evaluation of putative PI3K inhibitors.
359. The phenazine series. Part VI. Reactions of alkyl phenazonium salts; the phenazyls (1937)

H. McIlwain, J. Chem. Soc., 1937, 1704 DOI: 10.1039/JR9370001704
Initial Binding of Murine Leukemia Virus Particles to Cells Does Not Require Specific Env-Receptor Interaction (1999)

The initial step of virus-cell interaction was studied by immunofluorescence microscopy. Single particles of murine leukemia virus (MLV) vectors and human immunodeficiency virus (HIV) were visualized by immunofluorescence. Fluorescent dots representing single virions could be localized by staining of capsid proteins (CA) or surface envelope proteins (SU) after fixation of virus supernatants. This technique can be used to determine particle concentration in viral supernatants and also to study virus-cell interaction. We investigated the role of the Env-receptor interaction for the initial binding event between the cell and the viral particles. Ecotropic MLV vector particles were shown to bind to human cells which do not express the specific viral receptor. In addition, MLV particles defective for Env were shown to bind the cells similarly to infectious MLV. Time course experiments of virus-cell binding and dissociation showed identical profiles for infectious and Env-defective MLV particles and suggested that MLV Env is not involved in the early phases of attachment of virus to cells. The possible implication of cellular factors in enhancing viral binding and infectivity is discussed.
Synthesis and Pharmacological Characterization of O-Alkynyloximes of Tropinone and N-Methylpiperidinone as Muscarinic Agonists (1998)

A number of O-alkynyloximes of tropinone and N-methyl-4-piperidinone have been synthesized and evaluated for muscarinic activity. The affinities of these oximes were tested in homogenates of cerebral cortex, heart, and submandibulary glands from rats using [3H]pirenzepine and [3H]-N-methylscopolamine as radioligands. The oximes bind to the cortical muscarinic receptors with pKi values varying from 3 to 7. Higher binding affinities were observed for the O-alkynyl tropinone oximes than the corresponding piperidinone analogues. Binding to the muscarinic sites in the heart and submandibulary glands was also observed but with lower affinities. Good M1 subtype selectivity (10-fold or greater) was observed with some oximes (26a, 28a, 32a) at the cortical sites. These oximes also attenuated scopolamine-induced impairment of the water mask task in mice. Functional assays for M3 activity on the rat aorta showed that all oximes possessed M3 agonist action but M2 agonist activity was not observed at the endothelium-denuded rabbit aorta. Analysis of the quantitative structure-activity relationship (QSAR) indicated that the Connolly surface area is an important determinant of activity, accounting for 70% of the variation in cortical binding affinity among the oximes.
Technology trends of silicon-on-insulator-its advantages and problems to be solved (2002)

Recent progress in SOI technology is reviewed and problems which need be solved are discussed. Emphasis is placed on the substrate floating effect, for which the bandgap engineering method is proposed for the first time. It is demonstrated that Si-Ge formation in the source region can improve the drain breakdown voltage significantly.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Transcervical Approach With Protective Flow Reversal for Carotid Angioplasty and Stenting (2005)

Our initial experience demonstrates that a transcervical approach is a viable alternative for CAS. The procedure can be performed safely, with good initial clinical outcomes. The approach allows carotid flow reversal and emboli protection without introducing neuroprotection devices. The method appears best suited for patients at high risk for endarterectomy and transfemoral access.
Controlled/Living Radical Polymerization: State of the Art in 2005 (2006)

Recent progress and future challenges in Controlled/Living Radical Polymerization (CRP) are discussed. Stable free radical polymerization (SFRP), atom transfer radical polymerization (ATRP), and degenerate transfer processes, including reversible addition fragmentation transfer (RAFT) are the most successful CRP techniques. They enable preparation of new materials from readily available monomers under undemanding conditions. Future developments require better understanding structure-reactivity relationship and deeper insight into the reactive intermediates by spectroscopic and computational techniques. The precise relationship between the structure and properties of materials prepared by CRP is also needed. This study should include the effect of higher polydispersities and other imperfections to optimize cost-performance ratio. Fast growth of areas related to hybrids and bioconjugate materials is anticipated.
Amnion graft for treatment of congenital absence of the vagina (1984)

The successful application of an amniotic membrane graft in the treatment of congenital absence of the vagina is described. Follow up with vaginal smears and vaginal biopsies revealed that amnion when used alone with mesenchyme applied to the host gives protection to the underlying granulation tissue and facilitates epithelialization.
Duration and Magnitude of Hypotension and Monocyte Deactivation in Patients With Community-Acquired Pneumonia (2011)

The objective was to examine the relationship of duration and magnitude of arterial hypotension to subsequent cellular immune suppression and cytokinemia in patients hospitalized with community-acquired pneumonia (CAP). We studied an observational cohort of 525 subjects hospitalized after presenting to the emergency department with radiographic and clinical signs of CAP. We compared the duration and magnitude of hypotension, using the cardiovascular Sequential Organ Failure Assessment (CV SOFA) subscore, to day 3 monocyte expression of human leukocyte antigen-DR (mHLA-DR), a previously validated marker of cellular immune suppression. A significant association of CV SOFA with decreased mHLA-DR expression was present in univariate analysis (P < 0.001) and persisted after adjustment for illness severity and other covariates (P = 0.01). With CV SOFA separated into components of magnitude and duration, after covariate adjustment, only duration was associated with day 3 mHLA-DR expression (P = 0.03). Levels of key proinflammatory and anti-inflammatory cytokines (interleukin 6 [IL-6], IL-10, tumor necrosis factor) increased with hypotension exposure and were also associated with mHLA-DR expression. In patients admitted with CAP, arterial hypotension over the first 3 days is associated with markers of monocyte deactivation. The duration of exposure to hypotension may be more important than the magnitude, and monocyte deactivation correlates with IL-6 and IL-10 release. These results suggest that persistent hypotension might contribute to immunosuppression following septic shock.
The regulation of elevated EphA2 protein levels in metastatic cancer cells: Roles for ligand binding, protein degradation, and c -Cbl (2001)

A number of studies have shown that elevated protein tyrosine kinase activity is required for cancer metastasis. Knowledge of the specific tyrosine kinases that promote metastatic behaviors is therefore critical to understanding and treating cancer. One tyrosine kinase that is increasingly recognized to be a critical regulator of metastasis is the EphA2 receptor tyrosine kinase. EphA2 protein levels in human and canine models of prostate cancer were elevated in the most aggressive cancer cells. EphA2 immunoreactivity in vivo also was significantly greater in human prostate cancers as compared with benign prostate epithelium. Despite its elevated levels in cancer, the EphA2 on malignant cells demonstrated lower levels of ligand binding and tyrosine phosphorylation than the EphA2 on non-transformed epithelial cells. Metastatic cancer cells often have weak cell-cell adhesions, which prevent EphA2 from binding its cell-bound ligands on the surface of neighboring cells. Thus, we hypothesized that decreased EphA2-ligand binding may elevate EphA2 protein levels in metastatic cancer cells by preventing EphA2 protein degradation. Decreased EphA2-ligand binding is important because conditions that restore or mimic ligand binding decrease metastatic cell growth and invasiveness. EphA2 on metastatic cancer cells was stimulated, which caused the rapid internalization of EphA2 into endosomal vesicles as detected by immunofluorescence and electron microscopies. Western blot and pulse-chase analyses revealed a rapid and dramatic decrease in EphA2 protein levels following EphA2 stimulation. EphA2 stimulation also promoted an association between EphA2 and the c-Cbl adaptor protein as detected by co-immunoprecipitation and co-localization studies. These results demonstrate that stimulated EphA2 is internalized and degraded, and provide insight into the basic biochemical mechanism of stimulation induced EphA2 protein degradation. This information provides insight into the causes of elevated EphA2 protein levels in metastatic cancer cells and may assist in the design of therapeutic approaches to target the large number of metastatic human cancer cells that have elevated levels of EphA2 protein. EphA2 protein levels are also elevated following transformation of epithelial cells by oncogenic Ras. The mechanism through which Ras transformation increases EphA2 protein levels is not known but appears to be dependent upon the geranylgeranylation of certain cellular proteins.
FLAG assay as a novel method for real-time signal generation during PCR: application to detection and genotyping of KRAS codon 12 mutations (2007)

Real-time signal generation methods for detection and characterization of low-abundance mutations in genomic DNA are powerful tools for cancer diagnosis and prognosis. Mutations in codon 12 of the oncogene KRAS, for example, are frequently found in several types of human cancers. We have developed a novel real-time PCR technology, FLAG (FLuorescent Amplicon Generation) and adapted it for simultaneously (i) amplifying mutated codon 12 KRAS sequences, (ii) monitoring in real-time the amplification and (iii) genotyping the exact nucleotide alteration. FLAG utilizes the exceptionally thermostable endonuclease PspGI for real-time signal generation by cleavage of quenched fluorophores from the 5'-end of the PCR products and, concurrently, for selecting KRAS mutations over wild type. By including peptide-nucleic-acid probes in the reaction, simultaneous genotyping is achieved that circumvents the requirement for sequencing. FLAG enables high-throughput, closed-tube KRAS mutation detection down to approximately 0.1% mutant-to-wild type. The assay was validated on model systems and compared with allele-specific PCR sequencing for screening 27 cancer specimens. Diverse applications of FLAG for real-time PCR or genotyping applications in cancer, virology or infectious diseases are envisioned.
Identification of Immunologic Biomarkers Associated with Clinical Response after Immune‐Based Therapy for Cancer (2009)

The identification of immunologic biomarkers associated with clinical response after immune intervention for cancer is an area of intensive investigation. The field would benefit from a more systemic and directed approach for biomarker identification and evaluation. Lessons can be learned from other fields, such as cancer diagnostics, as to how to develop response-associated biomarkers. Studies in both human in vitro models as well as murine models of cancer can significantly inform and streamline the choice of candidates. Adoptive T-cell therapy is an interesting model for exploring potential immunologic surrogates that may predict clinical response. Most likely the clinical effectiveness of immune-based treatments will be predicted by panels of markers rather than single assays of a specific immune effector cell.
Introduction to Space-Time Wireless Communications (2003)

Wireless networks are under constant pressure to provide ever-higher data rates to increasing numbers of users with greater reliability. This book is an accessible introduction to every fundamental aspect of space-time wireless communications. Space-time processing technology is a powerful tool for improving system performance that already features in the UMTS and CDMA2000 mobile standards. The ideal volume for graduate students and professionals, it features homework problems and other supporting material on a companion website.
The influence of circulating anti-Müllerian hormone on ovarian responsiveness to ovulation induction with gonadotrophins in women with polycystic ovarian syndrome: a pilot study (2013)

PCOS women with markedly raised circulating AMH seem to be resistant to hMG ovulation induction and may require a higher starting dose.
Generalization to Novel Images in Upright and Inverted Faces (1996)

An image of a face depends not only on its shape, but also on the viewpoint, illumination conditions, and facial expression. A face recognition system must overcome the changes in face appearance induced by these factors. Two related questions were investigated: the capacity of the human visual system to generalize the recognition of faces to novel images, and the level at which this generalization occurs. This problem was approached by comparing the identification and generalization capacity for upright and inverted faces. For upright faces, remarkably good generalization to novel conditions was found. For inverted faces, the generalization to novel views was significantly worse for both new illumination and viewpoint, although the performance on the training images was similar to that on the upright condition. The results indicate that at least some of the processes that support generalization across viewpoint and illumination are neither universal (because subjects did not generalize as easily for inverted faces as for upright ones) nor strictly object specific (because in upright faces nearly perfect generalization was possible from a single view, by itself insufficient for building a complete object-specific model). It is proposed that generalization in face recognition occurs at an intermediate level that is applicable to a class of objects, and that at this level upright and inverted faces initially constitute distinct object classes.