gebhart/patrepeval huggingface dataset:
Albondin-mediated capillary permeability to albumin. Differential role of receptors in endothelial transcytosis and endocytosis of native and modified albumins. (1994)

Specific albumin binding to the surface of endothelium initiates its transcytosis across continuous endothelium via noncoated plasmalemmal vesicles. Past work has identified several putative albumin-binding proteins (SPARC, gp60, gp30, and gp18). In this study, we examined the specific role of these proteins in the binding of bovine serum albumin (BSA) to endothelium. The 60-kDa albumin-binding protein (gp60, now called albondin) was purified from cultured rat microvascular endothelial cells for antibody production. Anti-albondin antibodies (alpha gp60) specifically recognized albondin expressed by rat, bovine, and human endothelial cells (EC). alpha gp60 and unlabeled native BSA inhibited 125I-BSA binding to confluent EC monolayers and to both albondin and SPARC extracts immobilized on filters. Modification of BSA by maleic anhydride treatment (Mal-BSA) or by surface adsorption to colloidal gold particles (A-Au) renders the ligand specific for gp30 and gp18 while eliminating its ability to inhibit 125I-BSA binding to EC and to both albondin and SPARC extracts. Mal-BSA and A-Au interacted with EC via distinct binding sites not recognizing native BSA. EC internalization of 125I-BSA is inhibited by unlabeled BSA and alpha gp60 IgG but not nonimmune IgG, Mal-BSA, or A-Au. Conversely, internalization of modified BSA is inhibited by unlabeled modified BSA but not BSA or alpha gp60 IgG. Specific 125I-BSA transendothelial transport in rat lungs perfused in situ and for EC monolayers in vitro is inhibited (> or = 90%) by unlabeled BSA and alpha gp60 IgG but not nonimmune IgG and Mal-BSA. No specific transport of 125I-Mal-BSA is detected across bovine lung microvascular endothelial cell monolayers, only paracellular and/or fluid-phase transport. Low temperatures reduce BSA transport by 5-fold and Mal-BSA by 2-fold. Interestingly, 3-fold more native BSA is transported than Mal-BSA at 37 degrees C, whereas at 8-10 degrees C they are nearly equal, suggesting facilitation of BSA transport. Cumulatively, it appears that gp30 and gp18 mediate the binding, endocytosis, and degradation of modified albumins, whereas albondin mediates native albumin binding which significantly enhances its transcytosis and capillary permeability.
A Systems Approach to Specifying a High Reliability, High Quality Thick Film Passive Component for Hybrid, Multi-Chip Module and Surface Mount Applications (1998)

A quantitative analysis of thick film chip resistors is presented regarding design and construction. Critical reliability and performance data are compared for two techniques used to adjust final resistance tolerance — abrasive trimming and laser trimming. Additional enhanced performance characteristics are discussed for diamond sawing versus laser scribing methods of die separation, and 3-sided versus 5-sided surface mount terminations, including nickel barrier and solderability aspects. This analysis will provide vital information for component engineers working with parts specifications for thick film passive components. Additionally, specification guidelines are defined based upon each given packaging and electrical application for optimum performance and reliability of a thick film passive component. These guidelines are specified for applications involving epoxy die attach, eutectic die attach, wire bonding, and surface mount reflow soldering. Some typical pitfalls that occur when using an incorrectly specified component for a given application are discussed.
Selective inhibition of ADAM metalloproteases blocks HER-2 extracellular domain (ECD) cleavage and potentiates the anti-tumor effects of trastuzumab (2006)

The HER-2 receptor tyrosine kinase is an important regulator of cell proliferation and survival, and it is a clinically validated target of therapeutic intervention for HER-2 positive breast cancer patients. Its extracellular domain (ECD) is frequently cleaved by protease(s) in HER-2 overexpressing breast cancer patients, rendering the remaining membrane-bound portion (p95) a constitutively activated kinase. The presence of both serum ECD and cellular p95 protein has been linked to poor clinical outcome as well as reduced effectiveness of some therapeutic treatments. We have identified a series of potent, selective small molecule inhibitors of ADAM proteases, exemplified here by INCB003619, and demonstrate that these inhibitors effectively block HER-2 cleavage in HER-2 overexpressing human breast cancer cell lines. Intriguingly, when used in combination, INCB003619 dramatically enhances the antiproliferative activity of suboptimal doses of the anti-HER-2 antibody, trastuzumab, in HER-2 overexpressing/shedding breast cancer cell lines, accompanied by reduced ERK and AKT phosphorylation. Furthermore, INCB003619, in combination with trastuzumab, augments the pro-apoptotic and antiproliferative effects of the chemotherapeutic agent paclitaxel. Consistent with these in vitro data, INCB003619 reduces serum ECD levels and enhances the antitumor effect of trastuzumab in a xenograft tumor model derived from the HER-2 overexpressing BT-474 breast cancer cell line. Collectively, these findings suggest that blocking HER-2 cleavage with selective ADAM inhibitors may represent a novel therapeutic approach for treating HER-2 overexpressing breast cancer patients.
MYC-Dependent Regulation and Prognostic Role of CIP2A in Gastric Cancer (2009)

CIP2A immunopositivity is a predictor of survival for some subgroups of gastric cancer patients. CIP2A and MYC appear to be regulated in a positive feedback loop, wherein they promote each other's expression and gastric cancer cell proliferation.
Crystal structure of the CRISPR RNA–guided surveillance complex from Escherichia coli (2014)

Clustered regularly interspaced short palindromic repeats (CRISPRs) are essential components of RNA-guided adaptive immune systems that protect bacteria and archaea from viruses and plasmids. In Escherichia coli, short CRISPR-derived RNAs (crRNAs) assemble into a 405-kilodalton multisubunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defense). Here we present the 3.24 angstrom resolution x-ray crystal structure of Cascade. Eleven proteins and a 61-nucleotide crRNA assemble into a seahorse-shaped architecture that binds double-stranded DNA targets complementary to the crRNA-guide sequence. Conserved sequences on the 3' and 5' ends of the crRNA are anchored by proteins at opposite ends of the complex, whereas the guide sequence is displayed along a helical assembly of six interwoven subunits that present five-nucleotide segments of the crRNA in pseudo-A-form configuration. The structure of Cascade suggests a mechanism for assembly and provides insights into the mechanisms of target recognition.
Biology and Clinical Development of Vascular Endothelial Growth Factor–Targeted Therapy in Renal Cell Carcinoma (2004)

Therapeutic targeting of VEGF in RCC has strong biologic rationale and preliminary clinical efficacy. Further investigation will determine the optimal timing, sequence, and utility of these agents in RCC.
Monoclonal antibodies to murine gamma-interferon which differentially modulate macrophage activation and antiviral activity. (1985)

Four monoclonal IgG antibodies to purified, recombinant murine gamma-interferon (rIFN-gamma) have been produced by fusion of immune hamster splenocytes with HAT-sensitive murine myeloma cells. Specificity was confirmed either with an enzyme-linked immunosorbent assay (ELISA) that used immobilized rIFN-gamma or with a radioimmunoassay that employed soluble 125I-rIFN-gamma and heat-killed, fixed Staphylococcus aureus-bearing Protein A. Competition binding experiments suggested that the monoclonal antibodies (MoAb) displayed two distinct epitope specificities: one displayed by H1 and H2, and the other displayed by H21 and H22. By using murine-human recombinant IFN-gamma hybrid molecules, the H1/H2 epitope was shown to depend on the amino-terminus of IFN-gamma, whereas the H21/H22 epitope was formed by the carboxy-terminal amino acid sequence. The MoAb also reacted with natural IFN-gamma. When bound to a surface, all four MoAb, but not normal hamster IgG, removed 100% of the antiviral and MAF activities present in supernatants of cultures of the murine 24/G1 T cell hybridoma. In free solution, all four antibodies inhibited IFN-gamma dependent antiviral activity, but with different efficiencies. Soluble H21/H22 also blocked all of the 24/G1-derived activity that induces nonspecific tumoricidal activity in macrophages (MAF) while H1/H2 enhanced MAF activity. The differential inhibitory or enhancing activities of H21 or H1 reflected their ability to inhibit or enhance binding of 125I-rIFN-gamma to macrophages, respectively. Soluble H21/H22 and solid-phase H1/H2 inhibited 100% of the MAF, microbicidal, and Ia-inducing activities from lymphokine preparations produced by mitogen stimulation of normal murine splenic cells. These results help to establish definitive structure-function relationships for the IFN-gamma molecule, and indicate that IFN-gamma is the primary lymphokine responsible for inducing nonspecific tumoricidal activity and Ia antigen expression, and for enhancing microbicidal activity in macrophages.
Dietary Carotenoids and Vitamins A, C, and E and Risk of Breast Cancer (1999)

Consumption of fruits and vegetables high in specific carotenoids and vitamins may reduce premenopausal breast cancer risk.
Gastroesophageal Reflux Disease (2003)

Gastroesophageal reflux disease (GERD) is generally a lifelong illness that affects many people, but its significance is often underestimated. Chronic abnormal gastric reflux results in erosive esophagitis in up to 60% of patients with GERD. Esophageal stricture, Barrett's esophagus, and esophageal adenocarcinoma are the most serious complications of GERD. Although heartburn and acid regurgitation are the most common complaints, extraesophageal symptoms such as noncardiac chest pain, laryngitis, coughing, and wheezing can be manifestations of GERD. Unfortunately, the severity of symptoms is not a reliable indicator of the severity of erosive esophagitis. Endoscopy is the preferred method to diagnose and grade erosive esophagitis, and various classification systems are used to grade disease severity. The Los Angeles Classification is a valid and widely accepted system to evaluate the severity of erosive esophagitis. The immediate goals of treatment are to provide effective symptomatic relief and to achieve healing in patients with esophageal damage. The treatment regimen often begins by prescribing a therapy to reduce gastric acid secretion. A proton pump inhibitor is the preferred agent for many patients. Because GERD is a chronic, relapsing disease, long-term maintenance therapy is usually necessary to relieve symptoms, prevent complications, and improve the quality of life in patients with GERD.
High Tunnel Magnetoresistance at Room Temperature in Fully Epitaxial Fe/MgO/Fe Tunnel Junctions due to Coherent Spin-Polarized Tunneling (2004)

We fabricated fully epitaxial Fe(001)/MgO(001)/Fe(001) magnetic tunnel junctions (MTJs) and observed a magneto-resistance (MR) ratio of 88% at T = 293 K (146% at T = 20 K), the highest value yet reported. The origin of the high MR ratio is not the diffusive tunneling of Julliere's model but the coherent spin-polarized tunneling in epitaxial MTJs, in which only the electrons with totally symmetric wave functions with respect to the barrier-normal axis can tunnel. The bias-voltage dependence of the MR was very small, resulting in a high output voltage of 380 mV. This high voltage will help overcome problems in the development of high-density magnetoresistive random-access-memory (MRAM).
Two simple stopping criteria for turbo decoding (1999)

This paper presents two simple and effective criteria for stopping the iteration process in turbo decoding with a negligible degradation of the error performance. Both criteria are devised based on the cross-entropy (CE) concept. They are as efficient as the CE criterion, but require much less and simpler computations.
Acute Pancreatitis Results in Induction of Heat Shock Proteins 70 and 27 and Heat Shock Factor-1 (2000)

Heat shock proteins (HSPs) 70 and 27 are stress-responsive proteins that are important for cell survival after injury; the expression of these HSPs is regulated primarily by the transcription factor heat shock factor-1 (HSF-1). The purpose of this study was to determine the effect of acute pancreatitis on pancreatic HSPs (70, 27, 60, and 90) expression and to assess potential mechanisms for HSP induction using a murine model of cerulein-induced pancreatitis. We found an increase of both HSP70 and HSP27 levels with expression noted throughout the pancreas after induction of pancreatitis. HSP60 and HSP90 levels were constitutively expressed in the pancreas and did not significantly change with acute pancreatitis. HSF-1 DNA binding activity increased in accordance with increased HSP expression. We conclude that acute pancreatitis results in a marked increase in the expression of HSP70 and HSP27. Furthermore, the induction of HSP70 and HSP27 expression was associated with a concomitant increase in HSF-1 binding activity. The increased expression of both HSP70 and HSP27 noted with pancreatic inflammation may confer a protective effect for the remaining acini after acute pancreatitis.
Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new mutations and the paradox between genotype and phenotype. (1996)

Up to now eight patients with alpha-NAGA deficiency have been described. This includes the newly identified patient reported here who died unexpectedly aged 1 1/2 years of hypoxia during convulsions; necropsy was not performed. Three patients have been genotyped previously and here we report the mutations in the other five patients, including two new mutations (S160C and E193X). The newly identified patient is consanguineous with the first patients reported with alpha-NAGA deficiency and neuroaxonal dystrophy and they all had the alpha-NAGA genotype E325K/E325K. Clinical heterogeneity among patients with alpha-NAGA deficiency is extreme. Two affected sibs, homozygotes for E325K, are severely affected and have the signs and symptoms of infantile neuroaxonal dystrophy, but prominent vacuolisation is lacking. The mildly affected patients (two families, three patients) at the opposite end of the clinical spectrum have clear vacuolisation and angiokeratoma but no overt neurological manifestations. Two of them are homozygous for the stop mutation E193X, leading to complete loss of alpha-NAGA protein. These observations are difficult to reconcile with a simple genotype-phenotype correlation and we suggest that factors or genes other than alpha-NAGA contribute to the clinical heterogeneity of the eight patients with alpha-NAGA deficiency. At the metabolic level, the patients with alpha-NAGA deficiency are similar. The major abnormal urinary oligosaccharides are sialylglycopeptides of the O linked type. Our enzymatic studies indicated that these compounds are not the primary lysosomal storage products.
Combining Several Screening Tests: Optimality of the Risk Score (2002)

The development of biomarkers for cancer screening is an active area of research. While several biomarkers exist, none is sufficiently sensitive and specific on its own for population screening. It is likely that successful screening programs will require combinations of multiple markers. We consider how to combine multiple disease markers for optimal performance of a screening program. We show that the risk score, defined as the probability of disease given data on multiple markers, is the optimal function in the sense that the receiver operating characteristic (ROC) curve is maximized at every point. Arguments draw on the Neyman-Pearson lemma. This contrasts with the corresponding optimality result of classic decision theory, which is set in a Bayesian framework and is based on minimizing an expected loss function associated with decision errors. Ours is an optimality result defined from a strictly frequentist point of view and does not rely on the notion of associating costs with misclassifications. The implication for data analysis is that binary regression methods can be used to yield appropriate relative weightings of different biomarkers, at least in large samples. We propose some modifications to standard binary regression methods for application to the disease screening problem. A flexible biologically motivated simulation model for cancer biomarkers is presented and we evaluate our methods by application to it. An application to real data concerning two ovarian cancer biomarkers is also presented. Our results are equally relevant to the more general medical diagnostic testing problem, where results of multiple tests or predictors are combined to yield a composite diagnostic test. Moreover, our methods justify the development of clinical prediction scores based on binary regression.
Tamoxifen induces Na+ -dependent uridine transport and dome formation in a human breast tumor cell line. (2006)

The induction of a concentrative transport of uridine is a concomitant of cellular differentiation of breast tumor cells. These findings give added weight to evidence that uridine may play a regulatory role in the transition to the neoplastic state. The absence of the transporter and low intracellular uridine concentrations in the undifferentiated state may relate to 5-FU sensitivity of breast tumors. Induction of the transporter by tamoxifen and the consequent major increase in intracellular concentrations of free uridine suggests a potentially negative effect of tamoxifen on regimens containing 5-FU.
Tanshinone ( Salviae miltiorrhizae Extract) Preparations Attenuate Aminoglycoside-Induced Free Radical Formation In Vitro and Ototoxicity In Vivo (2003)

Antioxidant therapy protects against aminoglycoside-induced ototoxicity in animal models. A clinically suitable antioxidant must not affect the therapeutic efficacy of aminoglycosides or exhibit any side effects of its own. In addition, the treatment should be inexpensive and convenient in order to be implemented in developing countries where the use of aminoglycosides is most common. Standardized Salviae miltiorrhizae extracts (Danshen) are used clinically in China and contain diterpene quinones and phenolic acids with antioxidant properties. We combined in vitro and in vivo approaches to investigate the effect of a clinically approved injectable Danshen solution on aminoglycoside-induced free radical generation and ototoxicity. In vitro, Danshen inhibited gentamicin-dependent lipid peroxidation (formation of conjugated dienes from arachidonic acid), as well as the gentamicin-catalyzed formation of superoxide (in a lucigenin-based chemiluminescence assay) and hydroxyl radicals (oxidation of N,N-dimethyl-p-nitrosoaniline). Danshen extracts were then administered to adult CBA mice receiving concurrent treatment with kanamycin (700 mg/kg of body weight twice daily for 15 days). Auditory threshold shifts induced by kanamycin (approximately 50 dB) were significantly attenuated. Danshen did not reduce the levels in serum or antibacterial efficacy of kanamycin. These results suggest that herbal medications may be a significantly underexplored source of antidotes for aminoglycoside ototoxicity. Such traditional medicines are widely used in many developing countries and could become an easily accepted and inexpensive protective therapy.
Production of 3-hydroxypropionic acid from glycerol by acid tolerantEscherichia coli (2014)

The biological production of 3-hydroxypropionic acid (3-HP) has attracted significant attention because of its industrial importance. The low titer, yield and productivity, all of which are related directly or indirectly to the toxicity of 3-HP, have limited the commercial production of 3-HP. The aim of this study was to identify and select a 3-HP tolerant Escherichia coli strain among nine strains reported to produce various organic acids efficiently at high titer. When transformed with heterologous glycerol dehydratase, reactivase and aldehyde dehydrogenase, all nine E. coli strains produced 3-HP from glycerol but the level of 3-HP production, protein expression and activities of the important enzymes differed significantly according to the strain. Two E. coli strains, W3110 and W, showed higher levels of growth than the others in the presence of 25 g/L 3-HP. In the glycerol fed-batch bioreactor experiments, the recombinant E. coli W produced a high level of 3-HP at 460 ± 10 mM (41.5 ± 1.1 g/L) in 48 h with a yield of 31 % and a productivity of 0.86 ± 0.05 g/L h. In contrast, the recombinant E. coli W3110 produced only 180 ± 8.5 mM 3-HP (15.3 ± 0.8 g/L) in 48 h with a yield and productivity of 26 % and 0.36 ± 0.02 g/L h, respectively. This shows that the tolerance to and the production of 3-HP differ significantly among the well-known, similar strains of E. coli. The titer and productivity obtained with E. coli W were the highest reported thus far for the biological production of 3-HP from glycerol by E. coli.
Detection of Drugs in Saliva of Impaired Drivers (1984)

This study examined the feasibility of detecting drugs using saliva samples obtained from impaired drivers. Screening procedures on 1- to 2-mL samples were for cannabinoids, volatiles, benzodiazepines, and other acidic/neutral/basic drugs. Methodology consisted of enzyme multiple immunoassay technique (EMIT) and temperature programmed gas chromatography with confirmation by gas chromatography/mass spectrometry (GC/MS). Fifty-six samples were obtained from drivers arrested for suspicion of impaired driving. Other than alcohol, the major drugs detected were cannabinoids and diazepam. Cocaine was found in one case.
Glass fibers for stimulated Brillouin scattering and phase conjugation (2007)

Stimulated Brillouin scattering (SBS) and the laser-induced damage threshold (LIDT) in different multimode glass fibers with a core diameter of 200 μm are determined. Antireflective coatings for fiber end-faces with high LIDT are developed, which enhance the SBS reflectivity and reduce unwanted front-face reflections. The morphology of pump- and Stokes-radiation induced damages is investigated using atomic force microscopy.
Far-red fluorescent proteins evolved from a blue chromoprotein from Actinia equina (2005)

Proteins of the GFP (green fluorescent protein) family demonstrate a great spectral and phylogenetic diversity. However, there is still an intense demand for red-shifted GFP-like proteins in both basic and applied science. To obtain GFP-like chromoproteins with red-shifted absorption, we performed a broad search in blue-coloured Anthozoa species. We revealed specimens of Actinia equina (beadlet anemone) exhibiting a bright blue circle band at the edge of the basal disc. A novel blue chromoprotein, aeCP597, with an absorption maximum at 597 nm determining the coloration of the anemone basal disk was cloned. AeCP597 carries a chromophore chemically identical with that of the well-studied DsRed (red fluorescent protein from Discosoma sp.). Thus a strong 42-nm bathochromic shift of aeCP597 absorption compared with DsRed is determined by peculiarities of chromophore environment. Site-directed and random mutagenesis of aeCP597 resulted in far-red fluorescent mutants with emission maxima at up to 663 nm. The most bright and stable mutant AQ143 possessed excitation and emission maxima at 595 and 655 nm respectively. Thus aeCP597 and its fluorescent mutants set a new record of red-shifted absorption and emission maxima among GFP-like proteins.