gebhart/patrepeval huggingface dataset:
Hydrogen induced crack growth rate in steel plates under uniaxial stress (2013)

The purpose of this work was to determine in a quantitative manner the effect of an external uniaxial stress on the kinetics of the hydrogen induced cracking. In this study, the hydrogen induced cracking was done by cathodic charging of API–5L–X52 steel plates. The growth of the induced cracks was recorded at increasing inspection times by ultrasonic inspection. The external uniaxial stress affected the number of initial cracks in the HIC tests, having more initial cracks as the stress increases. This effect is related with the stress fields interaction from the internal pressure produced by the molecular hydrogen and the applied external stress, which weakens the interface between the matrix and the non-metallic inclusions, thus facilitating the nucleation of cracks by the pressure mechanism. A greater number of individual cracks causes that the number of cracks interconnections to increase, thus affecting the crack shape and growth. The external uniaxial stress, however did not show a significant effect on the hydrogen induced crack growth rate, at least in the interval of the applied stresses used in this work.
Mechanism-based design of prolactin receptor antagonists. (1993)

The mechanism of action of two forms of the prolactin (PRL) receptor was studied using analogs of human growth hormone (hGH). At low concentrations (approximately 1 pM), hGH binds and stimulates proliferation of Nb2 cells containing the 391-residue PRL receptor as well as murine lymphoid FDC-P1 cells transfected with the 591-residue hPRL receptor. However, at high concentrations (approximately 70 microM) hGH inhibits proliferation of both these cell lines. Such a "bell-shaped" hormone response curve was observed for hGH stimulation of the hGH receptor (Fuh, G., Cunningham, B.C., Fukunaga, R., Nagata, S., Goeddel, D. V., and Wells, J.A. (1992) Science 256, 1677-1680) and is consistent with the sequential formation of an active hormone-(receptor)2 complex in which hGH binds through a first site (Site 1) to a first receptor and then through a second site (Site 2) to a second receptor. By analogy to hGH activation of the hGH receptor, we find that hGH variants that are mutated in Site 1 or Site 2 are greatly reduced as agonists. Similarly, only Site 2 mutants are potent antagonists of either hGH or hPRL stimulated cell proliferation. These and other data support the notion that hGH and hPRL activate the PRL receptor by sequential dimerization and provide a rational basis for the design of potent antagonists to the prolactin receptor.
A novel role for RIP1 kinase in mediating TNFα production (2012)

Receptor-interacting protein 1 (RIP1) is a Ser/Thr kinase with both kinase-dependent and kinase-independent roles in death receptor signaling. The kinase activity of RIP1 is required for necroptosis, a caspase-independent pathway of programmed cell death. In some cell types, the inhibition of caspases leads to autocrine production of TNFα, which then activates necroptosis. Here, we describe a novel role for RIP1 kinase in regulating TNFα production after caspase inhibition. Caspase inhibitors activate RIP1 kinase and another protein, EDD, to mediate JNK signaling, which stimulates Sp1-dependent transcription of TNFα. This pathway is independent of nuclear factor κB and also occurs after Smac mimetic/IAP antagonist treatment or the loss of TNF receptor-associated factor 2 (Traf2). These findings implicate cIAP1/2 and Traf2 as negative regulators of this RIP1 kinase-dependent TNFα production pathway and suggest a novel role for RIP1 kinase in mediating TNFα production under certain conditions.
Microwave-assisted synthesis of potent PDE7 inhibitors containing a thienopyrimidin-4-amine scaffold (2014)

A series of novel thienopyrimidin-4-amines have been synthesized and evaluated as phosphodiesterase (PDE) inhibitors. A rationale for the observed selectivity against PDE7 has been obtained from molecular modelling studies on the most active compounds.
Exubera inhaled insulin: a review (2004)

The focus of this review is inhaled insulin, specifically Exubera, which represents a novel prandial insulin delivery method. Fear of hypoglycaemia and the reluctance of patients to use multiple daily injection regimens is a major barrier to achieving good glycaemic control in patients with type 1 and type 2 diabetes. Inhaled insulin has been developed to provide more physiological prandial insulin replacement than regular human insulin in patients with diabetes, with the advantage of non-invasive delivery. Good glycaemic control, comparable to modern subcutaneously administered insulin preparations, has already been demonstrated, and no unexpected safety concerns have been reported with inhaled insulin. The development of such insulin delivery technologies that are better tailored to patients' needs may improve patient compliance, thereby facilitating the attainment of treatment targets. This review summarises the studies available and discusses the potential implications to patients of needle-free insulin administration.
Steerable Microcatheters Actuated by Embedded Conducting Polymer Structures (1996)

Steerable microstructures, i.e., catheters, are presented. They exploit the electromechanochemical phenomena of ir-electron conjugated conducting polymers occurring when ionic species are exchanged with the surrounding medium. In this paper we considered polypyrrole as conducting polymer and a fast ionic conductor solid polyelectrolyte as ionic reservoir. Experimental determination of the governing material constants, modelling of conducting polymer/solid polyelectrolyte composite material and finite element computer simulations of the mechanical properties of cylindrical structures provide favourable indication about the feasibility of effective steerable, miniaturised catheters.
Training on a Tight Budget. (1994)

In mitosis, cells undergo a precisely orchestrated series of spatiotemporal changes in cytoskeletal structure to divide their genetic material. These changes are coordinated by a sophisticated network of protein-protein interactions and posttranslational modifications. In this study, we report a bifurcation in a signaling cascade of the NIMA-related kinases (Neks) Nek6, Nek7, and Nek9 that is required for the localization and function of two kinesins essential for cytokinesis, Mklp2 and Kif14. We demonstrate that a Nek9, Nek6, and Mklp2 signaling module controls the timely localization and bundling activity of Mklp2 at the anaphase central spindle. We further show that a separate Nek9, Nek7, and Kif14 signaling module is required for the recruitment of the Rho-interacting kinase citron to the anaphase midzone. Our findings uncover an anaphase-specific function for these effector kinesins that is controlled by specific Nek kinase signaling modules to properly coordinate cytokinesis.
Notch signaling in cardiac valve development and disease (2011)

The Notch pathway is an intercellular signaling mechanism involved in multiple cell-to-cell communication processes that regulate cell fate specification, differentiation, and tissue patterning during embryogenesis and adulthood. Functional studies in the mouse have shown that a Hey-Bmp2 regulatory circuit restricts Bmp2 expression to presumptive valve myocardium (atrioventricular canal and outflow tract). Likewise, a Notch-Hey-Bmp2 axis represses Bmp2 in the endocardium. During cardiac valve formation, endocardial Notch signaling activates the epithelial-mesenchyme transition (EMT) that will give rise to the cardiac valve primordia. During this process, Notch integrates with myocardially derived signals (Bmp2 or Bmp4) to promote, via Snail1/2 activation a complete, invasive EMT in presumptive valve tissue. In humans, mutations in Notch signaling components are associated with several congenital disorders involving malformed valves, aortic arch, and defective chamber septation. Data suggest that the same embryonic Notch-Hey-Bmp2 regulatory axis is active in the adult valve. This review examines the experimental evidence supporting a role for Notch in heart valve development and homeostasis, and how altered Notch signaling may lead to valve disease in the newborn and adult.
Is patient education helpful in providing care for patients with rheumatoid arthritis? A qualitative study involving French nurses (2013)

This French study explored nurses' involvement in patient education for patients with rheumatoid arthritis. The study design was qualitative. Semistructured interviews were conducted with 16 hospital nurses. Data analysis was performed according to Giorgi's descriptive phenomenological method, and supported by specific qualitative analysis software (Sphinx). The results showed the important role of hospital nurses in rheumatoid arthritis care. Patient education is a core part of nurses' work, allowing them to give patients information and emotional support. The interviewees displayed skills in helping patients learn to care for themselves. However, patient education mostly concerned patients who are already committed to their health care. Non-adherent patients warrant special attention; their acceptance of their disease, perceptions about disease and treatment, motivation, and autonomy should be specifically addressed. French nurses could benefit from more training, and could be aided by psychologists. Ambulatory services could also be developed for patient education in France, based on examples from other countries.
Inhibition of Interleukin-12 p40 Transcription and NF-κB Activation by Nitric Oxide in Murine Macrophages and Dendritic Cells (2004)

Nitric oxide (NO), an important effector molecule of the innate immune system, can also regulate adaptive immunity. In this study, the molecular effects of NO on the toll-like receptor signaling pathway were determined using interleukin-12 (IL-12) as an immunologically relevant target gene. The principal conclusion of these experiments is that NO inhibits IL-1 receptor-associated kinase (IRAK) activity and attenuates the molecular interaction between tumor necrosis factor receptor-associated factor-6 and IRAK. As a consequence, the NO donor S-nitroso-N-acetylpenicillamine (SNAP) inhibits lipopolysaccharide (LPS)-induced IL-12 p40 mRNA expression, protein production, and promoter activity in murine macrophages, dendritic cells, and the murine macrophage cell line RAW 264.7. Splenocytes from inducible nitric-oxide synthase-deficient mice demonstrate markedly increased IL-12 p40 protein and mRNA expression compared with wild type splenocytes. The inhibitory action of NO on IL-12 p40 is independent of the cytokine IL-10. The effects of NO can be directly attributed to inhibition of NF-kappaB activation through IRAK-dependent pathways. Accordingly, SNAP strongly reduces LPS-induced NF-kappaB DNA binding to the p40 promoter and inhibits LPS-induced IkappaB phosphorylation. Similarly, NO attenuates IL-1beta-induced NF-kappaB activation. These experiments provide another example of how an innate immune molecule may have a profound effect on adaptive immunity.
Learning layer-specific edges for segmenting retinal layers with large deformations (2016)

We present an algorithm for layer-specific edge detection in retinal optical coherence tomography images through a structured learning algorithm to reinforce traditional graph-based retinal layer segmentation. The proposed algorithm simultaneously identifies individual layers and their corresponding edges, resulting in the computation of layer-specific edges in 1 second. These edges augment classical dynamic programming based segmentation under layer deformation, shadow artifacts noise, and without heuristics or prior knowledge. We considered Duke's online data set containing 110 B-scans of 10 diabetic macular edema subjects with 8 retinal layers annotated by two experts for experimentation, and achieved a mean distance error of 1.38 pixels whereas that of the state-of-the-art was 1.68 pixels.
DC11: a novel monoclonal antibody revealing Alzheimer’s disease-specific tau epitope (2003)

Using tau protein extracts from Alzheimer's disease (AD) brain tissue, we generated a monoclonal antibody (mAb DC11) which decorated neurofibrillary pathology in brain derived from AD patients on immunohistochemistry, and which lacked reactivity with healthy brain tissue. The same pattern of DC11 specificity was observed on Western blot. The main constituent of structures decorated by DC11 is microtubule-associated protein tau. In Western blot, DC11 recognized neither native healthy tau nor its full length recombinant counterpart. However, the mAb showed strong immunoreactivity with truncated tau (residues tau151-421), thus indicating the requirement for a conformational epitope. Importantly, the DC11 epitope was phosphorylation independent. The immunochemical parameters of mAb show that DC11 could represent a novel structural probe with the specificity for conformation of pathological tau present in AD brains.
In Vitro Susceptibilities of Wild-Type or Drug-Resistant Hepatitis B Virus to (−)-β-d-2,6-Diaminopurine Dioxolane and 2′-Fluoro-5-Methyl-β-l-Arabinofuranosyluracil (2001)

Prolonged treatment of chronic hepatitis B virus (HBV) infection with lamivudine ([-]-beta-L-2',3'-dideoxy-3' thiacytidine) or famciclovir may select for viral mutants that are drug resistant due to point mutations in the polymerase gene. Determining whether such HBV mutants are sensitive to new antiviral agents is therefore important. We used a transient transfection system to compare the sensitivities of wild-type HBV and four lamivudine- and/or famciclovir-resistant HBV mutants to adefovir [9-(2-phosphonyl-methoxyethyl)-adenine; PMEA] and the nucleoside analogues (-)-beta-D-2, 6-diaminopurine dioxolane (DAPD) and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU). The drug-resistant mutants contained amino acid substitutions in the polymerase protein. We found that the M550I and M550V plus L526M substitutions, which confer lamivudine resistance, did not confer cross-resistance to adefovir or DAPD, but conferred cross-resistance to L-FMAU. The M550V substitution in isolation conferred a similar phenotype to M550I, except that it did not confer significant resistance to L-FMAU. The L526M substitution, which is associated with famciclovir resistance, conferred cross-resistance to L-FMAU but not to adefovir or DAPD. Inhibition of HBV secretion by DAPD, L-FMAU, and adefovir did not always correlate with inhibition of the generation of intracellular HBV replicative intermediates, suggesting that these analogs may preferentially inhibit specific stages of the viral replication cycle.
Characterization of a nonspecific activator protein for the enzymatic hydrolysis of glycolipids. (1988)

We have studied the substrate specificities of a non-specific activator protein on the enzymatic hydrolyses of the following compounds: GM1 and GM2, as well as several of their derivatives including oligosaccharides, GgOse3Cer-II3-sulfate and LacCer-II3-sulfate, Gb-Ose3Cer and GbOse4Cer, three neolacto-series glycosphingolipids, and two non-ceramide glycolipids. Our results show that this activator protein has a broad spectrum of activity and exhibits the properties of a nonspecific natural detergent. The evidence of non-specificity was the ability of this activator protein to stimulate the hydrolyses of glycolipids, regardless of glycosphingolipids or non-ceramide glycolipids, carried out by glycosidases from animals, plants, and microorganisms. Its activity was, however, limited to substrates that had a lipid moiety. The oligosaccharide of GM1 and deacetyl-fatty acid free GM1 (II3-NeuGg-Ose4-sphingosine) were hydrolyzed by beta-galactosidase in the absence of this activator protein.
Accurate Models for Microstrip Computer-Aided Design (1980)

Very accurate and simple equations are presented for both single and coupled microstrip lines' electrical parameters, i.e. impedances, effective dielectric constants, and attenuation including the effect of anisotropy in the substrate. For the single microstrip the effects of dispersion and non-zero strip thickness are also included.
Coherent frequency-domain reflectometry for characterization of single-mode integrated-optical waveguides (1993)

Based on the principles of optical frequency domain reflectometry (OFDR), a highly resolving and sensitive technique suitable for detecting, localizing, and quantifying weakly reflecting irregularities in single-mode optical waveguides is developed. A distributed feedback (DFB)-laser diode at lambda /sub 0/ equivalent to 1.3 mu m tuned within a range of Delta lambda equivalent to 6 nm and Delta v equivalent to 1 THz, respectively, is used as a source in the experimental arrangement. An auxiliary interferometer is employed so that the tuning need not be linear in time, in contrast to early implementations. At present, with waveguide structures on InP under test, a spatial resolution of 50 mu m and a dynamic range of about 60 dB are obtained. These data surpass OFDR results published so far. Prospects of closing the gap to coherence-domain reflectometric results and specific advantages make OFDR a promising technique.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Zebrafish: A Preclinical Model for Drug Screening (2002)

The zebrafish embryo has become an important vertebrate model for assessing drug effects. It is well suited for studies in genetics, embryology, development, and cell biology. Zebrafish embryos exhibit unique characteristics, including ease of maintenance and drug administration, short reproductive cycle, and transparency that permits visual assessment of developing cells and organs. Because of these advantages, zebrafish bioassays are cheaper and faster than mouse assays, and are suitable for large-scale drug screening. Here we describe the use of zebrafish bioassays for assessing toxicity, angiogenesis, and apoptosis. Using 18 chemicals, we demonstrated that toxic response, teratogenic effects, and LC(50) in zebrafish are comparable to results in mice. The effects of compounds on various organs, including the heart, brain, intestine, pancreas, cartilage, liver, and kidney, were observed in the transparent animals without complicated processing, demonstrating the efficiency of toxicity assays using zebrafish embryos. Using endogenous alkaline phosphatase staining and a whole-animal enzyme assay, we demonstrated that SU5416 and flavopiridol, compounds shown to have antiangiogenic effects in mammals, inhibit blood vessel growth in zebrafish, and this bioassay is suitable for high-throughput screening using a 96-well microplate reader. We also demonstrated that in vivo acridine orange staining can be used to visualize apoptotic events in embryos treated with brefeldin A, neomycin, or caspase inhibitors. After in vivo staining, acridine orange can be extracted and quantitated using a fluorescence microplate reader, providing a screening system for agents that modulate apoptosis.
A new SONOS memory using source-side injection for programming (1998)

We reported a new polysilicon-oxide-nitride-oxide-silicon (SONOS) nonvolatile memory using channel hot electron injection for high-speed programming. For the first time, we demonstrated that source-side injection technique, which is commonly used in floating gate nonvolatile memories for its high programming efficiency, can also be used in a SONOS device for achieving high-speed programming. Erase of the device is achieved by tunneling of electrons through the thin top oxide of the ONO charge storage stack. Since the thin top oxide is grown from the nitride layer, the self-saturated nature of the oxidation allows better thickness control. Endurance characteristics indicates that quality of the thin top grown from nitride is as good as the tunnel oxide grown from the silicon substrate. By increasing the top oxide thickness, it is possible to achieve ten years of retention requirement. The self-aligned sidewall gate structure allows small cell size for high density applications.
Modeling Latch-Up in CMOS Integrated Circuits (1982)

Latch-up is a common problem in CMOS integrated circuits. The modeling of latch-up with circuit simulation programs is addressed in this paper. The general features of a lumped element latch-up model are discussed along with a step-by-step approach to the component determination of the model. An example is presented to show the value of the latch-up model in latch-up threshold prediction. Finally, some latch-up control methods are discussed.
Endotoxin stimulates bronchial epithelial cells to release chemotactic factors for neutrophils. A potential mechanism for neutrophil recruitment, cytotoxicity, and inhibition of proliferation in bronchial inflammation (1991)

To test the effect of endotoxin on bronchial epithelial cells (BEC), BEC were isolated from bovine lungs and cultured in the presence of bacterial endotoxin. The BEC culture supernatant fluids were harvested, and neutrophil chemotactic activity (NCA) was determined with a blindwell chamber technique; cytotoxicity determined by lactate dehydrogenase release and BEC proliferation determined by Coulter counting. Endotoxin caused a dose- and time-dependent release of NCA from BEC cultures compared with media alone (82.3 +/- 8.1 vs 12.0 +/- 3.1 cells/high power field, p less than 0.001). To further characterize this activity, reverse phase HPLC analysis of release eicosanoid metabolites after [3H]arachidonic acid incorporation was performed. Endotoxin stimulated the release of the neutrophil chemoattractants, leukotriene B4 and 12-hydroxyeicosatetraenoic acids. Endotoxin also resulted in a dose and time dependent release of lactate dehydrogenase (42.9 +/- 4.2 vs 20.2 +/- 2.2 U/liter, p less than 0.001) although higher doses were required to cause cytotoxicity than to stimulate chemotaxis. Finally, endotoxin resulted in a dose dependent inhibition of BEC proliferation (176 x 10(3) +/- 16 x 10(3) vs 1,080 x 10(3) +/- 38 x 10(3) cells/ml measured at day 14, p less than 0.001). These data suggest that bacterial release of endotoxin may contribute to the pathophysiologic changes observed in bronchial inflammation by stimulating BEC to release NCA, denuding airway epithelium by causing cytotoxicity of BEC, and inhibiting epithelial repair by inhibiting BEC proliferation.
Nipah Virus Encephalitis Reemergence, Bangladesh (2004)

We retrospectively investigated two outbreaks of encephalitis in Meherpur and Naogaon, Bangladesh, which occurred in 2001 and We collected serum samples from persons who were ill, their household contacts, randomly selected residents, hospital workers, and various animals. Cases were classified as laboratory confirmed or probable. We identified 13 cases (4 confirmed, 9 probable) in Meherpur; 7 were in persons in two households. Patients were more likely than nonpatients to have close contact with other patients or have contact with a sick cow. In Naogaon, we identified 12 cases (4 confirmed, 8 probable); 7 were in persons clustered in 2 households. Two Pteropus bats had antibodies for Nipah virus. Samples from hospital workers were negative for Nipah virus antibodies. These outbreaks, the first since 1999, suggest that transmission may occur through close contact with other patients or from exposure to a common source.