gebhart/patrepeval huggingface dataset:
NanoLuc Complementation Reporter Optimized for Accurate Measurement of Protein Interactions in Cells (2015)

Protein-fragment complementation assays (PCAs) are widely used for investigating protein interactions. However, the fragments used are structurally compromised and have not been optimized nor thoroughly characterized for accurately assessing these interactions. We took advantage of the small size and bright luminescence of NanoLuc to engineer a new complementation reporter (NanoBiT). By design, the NanoBiT subunits (i.e., 1.3 kDa peptide, 18 kDa polypeptide) weakly associate so that their assembly into a luminescent complex is dictated by the interaction characteristics of the target proteins onto which they are appended. To ascertain their general suitability for measuring interaction affinities and kinetics, we determined that their intrinsic affinity (KD = 190 μM) and association constants (kon = 500 M(-1) s(-1), koff = 0.2 s(-1)) are outside of the ranges typical for protein interactions. The accuracy of NanoBiT was verified under defined biochemical conditions using the previously characterized interaction between SME-1 β-lactamase and a set of inhibitor binding proteins. In cells, NanoBiT fusions to FRB/FKBP produced luminescence consistent with the linear characteristics of NanoLuc. Response dynamics, evaluated using both protein kinase A and β-arrestin-2, were rapid, reversible, and robust to temperature (21-37 °C). Finally, NanoBiT provided a means to measure pharmacology of kinase inhibitors known to induce the interaction between BRAF and CRAF. Our results demonstrate that the intrinsic properties of NanoBiT allow accurate representation of protein interactions and that the reporter responds reliably and dynamically in cells.
An Introduction to Metal Matrix Composites (1993)

Metal matrix composites constitute a new class of materials, now starting to make a major industrial impact in fields as diverse as aerospace, automotives and electronics. This book gives a comprehensive, integrated coverage of these materials, including the background to analytical-, experimental-, production and application-oriented aspects. Clear pictorial descriptions are given of the basic principles governing various properties and characteristics; these encompass mechanical, thermal, electrical, environmental and wear behaviour. Coverage also extends to material processing and component fabrication aspects and to a survey of commercial usage. This book is aimed primarily at scientists, engineers, production managers and all those involved in research on new materials in general, and metal matrix composites in particular, but may also be suitable for use as a text in beginning graduate and advanced undergraduate courses.
Activation of β-catenin by carcinogenic Helicobacter pylori (2005)

Persistent gastritis induced by Helicobacter pylori is the strongest known risk factor for adenocarcinoma of the distal stomach, yet only a fraction of colonized persons ever develop gastric cancer. The H. pylori cytotoxin-associated gene (cag) pathogenicity island encodes a type IV secretion system that delivers the bacterial effector CagA into host cells after bacterial attachment, and cag+ strains augment gastric cancer risk. A host effector that is aberrantly activated in gastric cancer precursor lesions is beta-catenin, and activation of beta-catenin leads to targeted transcriptional up-regulation of genes implicated in carcinogenesis. We report that in vivo adaptation endowed an H. pylori strain with the ability to rapidly and reproducibly induce gastric dysplasia and adenocarcinoma in a rodent model of gastritis. Compared with its parental noncarcinogenic isolate, the oncogenic H. pylori strain selectively activates beta-catenin in model gastric epithelia, which is dependent on translocation of CagA into host epithelial cells. Beta-catenin nuclear accumulation is increased in gastric epithelium harvested from gerbils infected with the H. pylori carcinogenic strain as well as from persons carrying cag+ vs. cag- strains or uninfected persons. These results indicate that H. pylori-induced dysregulation of beta-catenin-dependent pathways may explain in part the augmentation in the risk of gastric cancer conferred by this pathogen.
Aspiration catheter for percutaneous thrombectomy: clinical results. (1990)

The clinical application of an aspiration thrombectomy system is presented. The system consists of a 7-F Teflon catheter with a rotating coaxial propeller-tipped wire. Thrombectomy was successful in treating occlusion of two femoropopliteal arteries and one hemodialysis implant but was not completely successful in a draining shunt vein. Preliminary results are encouraging; mechanical thrombectomy may offer an alternative to local lysis therapy.
Lidocaine toxicity. (1998)

Local anesthetics are the most commonly used drugs in dentistry. The number of adverse reactions reported, particularly toxic reactions, are extraordinarily negligible. This article reports a case of lidocaine toxicity with its typical manifestation in a 37-yr-old healthy male. The toxic reaction followed transoral/transpharyngeal topical spraying of lidocaine preoperatively during preparation for general anesthesia. A review of dosages of the most commonly used local anesthetic drugs in dentistry and the management of a toxic reaction is presented. Clinicians need to be in a position to recognize and successfully manage this potential adverse reaction.
Optimum element spacings for Yagi-Uda arrays (1973)

A method is developed for the maximization of the forward gain of a Yagi-Uda array by adjusting the interelement spacings. The effects of a finite dipole radius and the mutual coupling between the elements are taken into consideration. Currents in the array elements are approximated by three-term expansions with complex coefficients which convert the governing integral equations into simultaneous algebraic equations. The array gain is maximized by the repeated application of a perturbation procedure which converges rapidly to yield a set of optimum, generally unequal, element spacings. This method eliminates the need for a haphazard trial-and-error approach or for interpreting a vast data collection. Illustrative examples are given.
Fabrication of hollow glass microspheres used for ICF targets by dried-gel method (2006)

The parameters that affect the transformation process from dried-gel to microshell and the hollow glass microsphere(HGM) quality were investigated.The results show that increasing the volume fraction of Helium in furnace atmosphere can raise HGM yield and aspect ratio,but increasing the volume fraction of Argon properly is favorable for HGM surface finish.Decreasing furnace atmosphere pressure will increase HGM aspect ratio. HGM yield and quality increase with the increase of the furnace atmosphere temperature.When the volume fraction of helium in furnace atmosphere ranges from 50% to 80%,the furnace atmosphere pressure from 0.75×10~5 Pa to 1.00×10~5 Pa, the furnace atmosphere temperature from 1 500 ℃ to 1 650 ℃,high-quality HGM can be fabricated with high yield.Under the above optimized fabrication process parameters,hollow glass microspheres with a diameter of 100~500 μm,a wall thickness of 0.5~3.0 μm,a surface finish better than 5 nm,a concentricity better than 97%,a sphericity higher than 99% were fabricated,whose geometric characteristics,surface finish and failure pressures meet the stringent requirements for ICF targets.
Electro-anatomic mapping systems in arrhythmias (2008)

Electroanatomic mapping systems have permitted and facilitated difficult interventional ablation procedures for more than a decade. Initially, their use has been in arrhythmias in which the ablation target is difficult to identify, such as ventricular tachycardias in structural heart disease, atypical atrial flutters, or arrhythmias in patients with complex congenital heart defects. In the recent years, electroanatomic mapping systems have also been used to guide catheter-based isolation of the pulmonary veins, an important component of the modern management of atrial fibrillation (AF). Electroanatomic mapping systems integrate three important functionalities, namely (i) non-fluoroscopic localization of electrophysiological catheters in three-dimensional (3D) space; (ii) analysis and 3D display of activation sequences computed from local or calculated electrograms, and 3D display of electrogram voltage ('scar tissue'); and (iii) integration of this 'electroanatomic' information with non-invasive images of the heart (mainly computed tomography or magnetic resonance images). Although better understanding and ablation of complex arrhythmias mostly relies on the 3D integration of catheter localization and electrogram-based information to illustrate re-entrant circuits or areas of focal initiation of arrhythmias, the use of electroanatomic mapping systems in AF is currently based on integration of anatomic images of the left atrium and non-fluoroscopic visualization of the ablation catheter. Their use in the treatment of AF is mainly driven by safety considerations such as shorter fluoroscopy and procedure times, or visualization of cardiac (pulmonary veins) and extra-cardiac (oesophagus) structures that need to be protected during the procedure. In the future, the use of magnetic resonance images, and potentially of high-quality 3D ultrasound images, could provide anatomic information without ionizing radiation and may be helpful to visualize left atrial scar tissue.
An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance (2012)

We have developed a robust EMT signature that predicts resistance to EGFR and PI3K/Akt inhibitors, highlights different patterns of drug responsiveness for epithelial and mesenchymal cells, and identifies Axl as a potential therapeutic target for overcoming EGFR inhibitor resistance associated with the mesenchymal phenotype.
Oxidative stress in the denervated muscle (2010)

Following experimental hind limb denervation in rats, this study demonstrates that oxidative stress occurs and advances an hypothesis about its origin. In fact: (i) ROS are formed; (ii) membrane lipids are oxidized; (iii) oxidized ion channels and pumps may lead to increased [Ca(2+)](i); all the above mentioned events increase with denervation time. In the denervated muscle, (iv) mRNA abundance of cytoprotective and anti-oxidant proteins (Hsp70, Hsp27, Sod1, Catalase, Gpx1, Gpx4, Gstm1), as well as (v) SOD1 enzymatic activity and HSP70i protein increase; (vi) an unbalance in mitochondrial OXPHOS enzymes occurs, presumably leading to excess mitochondrial ROS production; (vii) increased cPLA2alpha expression (mRNA) and activation (increased [Ca(2+)](i)) may lead to increased hydroperoxides release. Since anti-oxidant defences appear inadequate to counterbalance increased ROS production with increased denervation time, an anti-oxidant therapeutic strategy seems to be advisable in the many medical conditions where the nerve-muscle connection is impaired.
Identification of an Astrocyte Cell Population from Human Brain that Expresses Perforin, a Cytotoxic Protein Implicated in Immune Defense (1998)

The brain is an immunoprivileged organ isolated from the peripheral immune system. However, it has been shown that resident cells, notably astrocytes and microglia, can express numerous innate immune molecules, providing the capacity to generate a local antipathogen system. Perforin is a cytolytic protein present in the granules of cytotoxic T lymphocytes and natural killer cells. Expression in cells other than those of the hemopoetic lineage has not been described. We report here that fetal astrocytes in culture (passages 2 to 15), astrocytoma, and adult astrocytes expressed perforin. Reverse transcriptase polymerase chain reaction followed by Southern blot was carried out using multiple specific primers and all cDNAs were cloned and sequenced. Human fetal astrocyte perforin cDNA sequence was approximately 100% identical to the reported perforin cDNA cloned from T cells. Western blot analysis using monoclonal and polyclonal antiperforin peptide antibodies revealed a protein of 65 kD in both human fetal astrocyte and rat natural killer cell lysates (n = 4). Immunostaining followed by FACS(R) and confocal and electron microscopy analysis revealed that perforin was expressed by 40-50% of glial fibrillary acidic protein positive cells present in the fetal brain culture (n = 11). Perforin was not localized to granules in astrocytes but was present throughout the cytoplasm, probably in association with the endoplasmic reticulum. Perforin was not detected in normal adult brain tissue but was present in and around areas of inflammation (white and grey matter) in multiple sclerosis and neurodegenerative brains. Perforin-positive cells were identified as reactive astrocytes. These findings demonstrate that perforin expression is not unique to lymphoid cells and suggest that perforin produced by a subpopulation of astrocytes plays a role in inflammation in the brain.
Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma (2017)

Pembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. (Funded by Merck; KEYNOTE-045 ClinicalTrials.gov number, NCT02256436 .).
Isolation of Candida tropicalis auxotrophic mutants (1990)

An enrichment scheme using nystatin was designed for the isolation of auxotrophic mutants from the diploid-alkane-utilizing yeast Candida tropicalis. A collection of 194 auxotrophs representing 7 phenotypes was isolated. One class of mutants was identified as having a defect in histidinol dehydrogenase activity and a second class of mutants was identified as having a defect in orotidine monophosphate decarboxylase activity. These strains are good candidates to be carrying mutations corresponding to the HIS4 and URA3 genes of Saccharomyces cerevisiae.
Overexpression and gene amplification of BAG‐1L in hormone‐refractory prostate cancer (2007)

BAG-1L (Bcl-2-associated anthanogene 1) has been found to interact with androgen receptor (AR), and has been suggested to be involved in the development of prostate cancer. In order to determine the presence of genetic and/or expression alterations of BAG-1L in prostate cancer, we analysed human prostate cancer cell lines and xenografts as well as patient samples of untreated, hormone-naïve, and hormone-refractory prostate carcinomas for sequence variations using denaturing high-performance liquid chromatography (DHPLC), for gene copy number using fluorescence in situ hybridization (FISH), and for expression using both quantitative RT-PCR and immunostaining. Only one sequence variation was found in all 37 cell lines and xenografts analysed. BAG-1 gene amplification was detected in two xenografts. In addition, gene amplification was found in 6 of 81 (7.4%) hormone-refractory clinical tumours, whereas no amplification was found in any of the 130 untreated tumours analysed. Additionally, gain of the BAG-1 gene was observed in 27.2% of the hormone-refractory tumours and in 18.5% of the untreated carcinomas. In a set of 263 patient samples, BAG-1L protein expression was significantly higher in hormone-refractory tumours than in primary tumours (p = 0.002). Altogether, these data suggest that amplification and overexpression of BAG-1L may be involved in the progression of prostate cancer.
Insulin receptor substrate‐2 is expressed in kidney epithelium and up‐regulated in diabetic nephropathy (2013)

Diabetic nephropathy (DN) is a progressive fibrotic condition that may lead to end-stage renal disease and kidney failure. Transforming growth factor-β1 and bone morphogenetic protein-7 (BMP7) have been shown to induce DN-like changes in the kidney and protect the kidney from such changes, respectively. Recent data identified insulin action at the level of the nephron as a crucial factor in the development and progression of DN. Insulin requires a family of insulin receptor substrate (IRS) proteins for its physiological effects, and many reports have highlighted the role of insulin and IRS proteins in kidney physiology and disease. Here, we observed IRS2 expression predominantly in the developing and adult kidney epithelium in mouse and human. BMP7 treatment of human kidney proximal tubule epithelial cells (HK-2 cells) increases IRS2 transcription. In addition, BMP7 treatment of HK-2 cells induces an electrophoretic shift in IRS2 migration on SDS/PAGE, and increased association with phosphatidylinositol-3-kinase, probably due to increased tyrosine/serine phosphorylation. In a cohort of DN patients with a range of chronic kidney disease severity, IRS2 mRNA levels were elevated approximately ninefold, with the majority of IRS2 staining evident in the kidney tubules in DN patients. These data show that IRS2 is expressed in the kidney epithelium and may play a role in the downstream protective events triggered by BMP7 in the kidney. The specific up-regulation of IRS2 in the kidney tubules of DN patients also indicates a novel role for IRS2 as a marker and/or mediator of human DN progression.
Murine Model of Niemann-Pick C Disease: Mutation in a Cholesterol Homeostasis Gene (1997)

An integrated human-mouse positional candidate approach was used to identify the gene responsible for the phenotypes observed in a mouse model of Niemann-Pick type C (NP-C) disease. The predicted murine NPC1 protein has sequence homology to the putative transmembrane domains of the Hedgehog signaling molecule Patched, to the cholesterol-sensing regions of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and SREBP cleavage-activating protein (SCAP), and to the NPC1 orthologs identified in human, the nematode Caenorhabditis elegans, and the yeast Saccharomyces cerevisiae. The mouse model may provide an important resource for studying the role of NPC1 in cholesterol homeostasis and neurodegeneration and for assessing the efficacy of new drugs for NP-C disease.
Studies of the Mechanism of the Antidiarrheal Effect of Codeine (1982)

To determine whether the antidiarrheal action of opiate drugs in humans is due to enhanced intestinal absorption rates, as suggested by recent experiments in animals, or is due to altered intestinal motility, as traditionally thought, we studied the effect of therapeutic doses of codeine on experimental diarrhea and on the rate of intestinal absorption of water and electrolytes in normal human subjects. Our results show that codeine (30-60 mg i.m.) markedly reduced stool volume during experimental diarrhea induced by rapid intragastric infusion of a balanced electrolyte solution. There was, however, no evidence that codeine stimulated the rate of intestinal absorption in the gut as a whole or in any segment of the gastrointestinal tract, either in the basal state or when absorption rates were reduced by intravenous infusion of vasoactive intestinal polypeptide. We also measured segmental transit times to determine whether and where codeine delayed the passage of fluid through the intestine. Codeine caused a marked slowing of fluid movement through the jejunum, but had no effect on the movement of fluid through the ileum or colon. In other studies, we found that the opiate antagonist naloxone did not significantly affect water or electrolyte absorption rates in the jejunum or ileum. We conclude (a) that therapeutic doses of codeine increase net intestinal absorption (and thereby reduce stool volume) by increasing the contact time of luminal fluid with mucosal cells, not by increasing the rate of absorption by the mucosal cells; and (b) that endogenous opiates do not regulate intestinal absorption in humans.
Analytical Chemistry of Nitric Oxide (2009)

Nitric oxide (NO) is the focus of intense research primarily because of its wide-ranging biological and physiological actions. To understand its origin, activity, and regulation, accurate and precise measurement techniques are needed. Unfortunately, analytical assays for monitoring NO are challenged by NO's unique chemical and physical properties, including its reactivity, rapid diffusion, and short half-life. Moreover, NO concentrations may span the picomolar-to-micromolar range in physiological milieus, requiring techniques with wide dynamic response ranges. Despite such challenges, many analytical techniques have emerged for the detection of NO. Herein, we review the most common spectroscopic and electrochemical methods, with a focus on the underlying mechanism of each technique and on approaches that have been coupled with modern analytical measurement tools to create novel NO sensors.
Identification of Quantitative Trait Loci for Production Traits in Commercial Pig Populations (2003)

The aim of this study was to investigate methods for detecting QTL in outbred commercial pig populations. Several QTL for back fat and growth rate, previously detected in experimental resource populations, were examined for segregation in 10 different populations. Two hundred trait-by-population-by-chromosome tests were performed, resulting in 20 tests being significant at the 5% level. In addition, 53 QTL tests for 11 meat quality traits were declared significant, using a subset of the populations. These results show that a considerable amount of phenotypic variance observed in these populations can be explained by major alleles segregating at several of the loci described. Thus, despite a relatively strong selection pressure for growth and back fat traits in these populations, these alleles have not yet reached fixation. The approaches used here demonstrate that it is possible to verify segregation of QTL in commercial populations by limited genotyping of a selection of informative animals. Such verified QTL may be directly exploited in marker-assisted selection (MAS) programs in commercial populations and their molecular basis may be revealed by positional candidate cloning.
Arginine Biosynthesis in Escherichia coli (2007)

A basic challenge in cell biology is to understand how interconnected metabolic pathways are regulated to provide the adequate cellular outcome when changing levels of metabolites and enzyme expression. In Escherichia coli, the arginine and pyrimidine biosynthetic pathways are connected through a common metabolite provided by a single enzyme. The different elements of the arginine biosynthetic system of Escherichia coli, including the connection with pyrimidine biosynthesis, and the principal regulatory mechanisms operating at genetic and enzymatic levels were integrated in a mathematical model using a molecular kinetic approach combined with a modular description of the system. The model was then used to simulate a set of perturbed conditions as follows: genetic derepression, feedback resistance of the first enzymatic step, and low constitutive synthesis of the intermediate carbamyl phosphate. In all cases, an excellent quantitative agreement between simulations and experimental results was found. The model was used to gain further insight into the function of the system, including the synergy between the different regulations. The outcome of combinations of perturbations on cellular arginine concentration was predicted accurately, establishing the model as a powerful tool for the design of arginine-overproducing strains.