gebhart/patrepeval huggingface dataset:
Reconstitution of I KATP : An Inward Rectifier Subunit Plus the Sulfonylurea Receptor (1995)

A member of the inwardly rectifying potassium channel family was cloned here. The channel, called BIR (Kir6.2), was expressed in large amounts in rat pancreatic islets and glucose-responsive insulin-secreting cell lines. Coexpression with the sulfonylurea receptor SUR reconstituted an inwardly rectifying potassium conductance of 76 picosiemens that was sensitive to adenosine triphosphate (ATP) (IKATP) and was inhibited by sulfonylureas and activated by diazoxide. The data indicate that these pancreatic beta cell potassium channels are a complex composed of at least two subunits--BIR, a member of the inward rectifier potassium channel family, and SUR, a member of the ATP-binding cassette superfamily. Gene mapping data show that these two potassium channel subunit genes are clustered on human chromosome 11 at position 11p15.1.
High-sensitivity two-color detection of double-stranded DNA with a confocal fluorescence gel scanner using ethidium homodimer and thiazole orange (1991)

Ethidium homodimer (EthD; lambda Fmax 620 nm) at EthD:DNA ratios up to 1 dye:4-5 bp forms stable fluorescent complexes with double-stranded DNA (dsDNA) which can be detected with high sensitivity using a confocal fluorescence gel scanner (Glazer, A.N., Peck, K. & Mathies, R.A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3851-3855). However, on incubation with unlabeled DNA partial migration of EthD takes place from its complex with dsDNA to the unlabeled DNA. It is shown here that this migration is dependent on the fractional occupancy of intercalating sites in the original dsDNA-EthD complex and that there is no detectable transfer from dsDNA-EthD complexes formed at 50 bp: 1 dye. The monointercalator thiazole orange (TO; lambda Fmax 530 nm) forms readily dissociable complexes with dsDNA with a large fluorescence enhancement on binding (Lee, L.G., Chen, C. & Liu, L.A. (1986) Cytometry 7, 508-517). However, a large molar excess of TO does not displace EthD from its complex with dsDNA. When TO and EthD are bound to the same dsDNA molecule, excitation of TO leads to efficient energy transfer from TO to EthD. This observation shows the practicability of 'sensitizing' EthD fluorescence with a second intercalating dye having a very high absorption coefficient and efficient energy transfer characteristics. Electrophoresis on agarose gels, with TO in the buffer, of preformed linearized M13mp18 DNA-EthD complex together with unlabeled linearized pBR322 permits sensitive fluorescence detection in the same lane of pBR322 DNA-TO complex at 530 nm and of M13mp18 DNA-EthD complex at 620 nm. These observations lay the groundwork for the use of stable DNA-dye intercalation complexes carrying hundreds of chromophores in two-color applications such as the physical mapping of chromosomes.
Clinical pharmacology of the novel marine-derived anticancer agent Ecteinascidin 743 administered as a 1- and 3-h infusion in a phase I study (2002)

Ecteinascidin 743 (ET-743) is an anticancer agent derived from the Caribbean tunicate Ecteinascidia turbinata. In the present article, the pharmacokinetics and pharmacodynamics of ET-743 are described within a phase I study. Forty patients with solid tumors initially received ET-743 as a 1-h i.v. infusion every 21 days at nine dose levels (50-1100 microg/m(2)). The maximal tolerated dose (MTD) was 1100 microg/m(2), with thrombocytopenia and fatigue as dose-limiting toxicities (DLTs). As this MTD was substantially lower than in parallel phase I studies, dose escalation continued using a prolonged, 3-h infusion. Thirty-two patients were entered at five dose levels (1000-1800 microg/m(2)). The MTD was 1800 microg/m(2) with pancytopenia and fatigue as DLTs. The recommended phase II dose was 1650 microg/m(2) given over 3 h at which 12 patients were treated. Pharmacokinetic monitoring was performed for both treatment schedules. Non-compartmental pharmacokinetic parameters at the recommended dose with the 3-h infusion were (mean value+/-SD): clearance 87+/-30 l/h and mean elimination half-life 26+/-7 h. Pharmacokinetics were linear at the dose range tested with this schedule. The percentage decrease in platelets, white blood cells and neutrophils correlated with the area under the plasma concentration versus time curve (AUC), dose and maximal plasma concentration (C(max)). Hepatic toxicity increased with dose, AUC and C(max). Administration of 1650 microg/m(2) ET-743 over 3 h seemed clinically feasible; pharmacokinetics were linear with this schedule. Hepatic and hematological toxicities correlated with exposure to ET-743.
High level of cFLIP correlates with resistance to death receptor-induced apoptosis in bladder carcinoma cells. (2003)

cFLIP is an important determinant of susceptibility to death receptor-induced apoptosis in bladder carcinomas and could function as a prognostic marker for death receptor sensitivity in future immune therapy.
Interpreting the Sounds of Swallowing: Fluid Flow through the Cricopharyngeus (1990)

The sounds of swallowing in normal subjects were recorded by means of a miniature accelerometer on the throat, simultaneously with videofluoroscopy of a modified barium swallow. Consistent correspondence was found between a rapid change in the acoustic spectrum of the accelerometer signal (the appearance of a region of energy prominence above 1,000 Hz) and bolus flow through the cricopharyngeus.
Analyses of volatile organic compounds from human skin (2008)

The natural variation in nonaxillary skin odorants described in this study provides a baseline of compounds we have identified from both endogenous and exogenous sources. Although complex, the profiles of volatile constituents suggest that the two body locations share a considerable number of compounds, but both quantitative and qualitative differences are present. In addition, quantitative changes due to ageing are also present. These data may provide future investigators of skin VOCs with a baseline against which any abnormalities can be viewed in searching for biomarkers of skin diseases.
Arginine-rich Anti-vascular Endothelial Growth Factor Peptides Inhibit Tumor Growth and Metastasis by Blocking Angiogenesis (2000)

Tumor angiogenesis is a critical step for the growth and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) is a specific and potent angiogenic factor and contributes to the development of solid tumors by promoting tumor angiogenesis. Therefore, it is a prime therapeutic target for the development of antagonists for treatment of cancer. We identified from peptide libraries arginine-rich hexapeptides that inhibit the interaction of VEGF(165) with VEGF receptor (IC(50) = 2-4 micrometer). They have no effect on binding of basic fibroblast growth factor to cellular receptor. The hexapeptides inhibit the proliferation of human umbilical vein endothelial cells induced by VEGF(165) without toxicity. The peptides bind to VEGF and inhibit binding of both VEGF(165) and VEGF(121), suggesting that the peptides interact with the main body of VEGF but not the heparin-binding domain that is absent in VEGF(121). The identified peptides block the angiogenesis induced by VEGF(165) in vivo in the chick chorioallantoic membrane and the rabbit cornea. Furthermore, one of the hexapeptides, RRKRRR, blocks the growth and metastasis of VEGF-secreting HM7 human colon carcinoma cells in nude mice. Based on our results, the arginine-rich hexapeptides may be effective for the treatment of various human tumors and other angiogenesis-dependent diseases that are related to the action of VEGF and could also serve as leads for development of more effective drugs.
Electrolysis in liquid ammonia solution in peptide chemistry (1969)

An adaptation of an electrolytic method is suggested for the removal of protecting groups in peptide chemistry. Some initial experiments are reported indicating the scope and possible limitations of the method.
A promiscuous split intein with expanded protein engineering applications (2017)

The protein <i>trans</i>-splicing (PTS) activity of naturally split inteins has found widespread use in chemical biology and biotechnology. However, currently used naturally split inteins suffer from an "extein dependence," whereby residues surrounding the splice junction strongly affect splicing efficiency, limiting the general applicability of many PTS-based methods. To address this, we describe a mechanism-guided protein engineering approach that imbues ultrafast DnaE split inteins with minimal extein dependence. The resulting "promiscuous" inteins are shown to be superior reagents for protein cyclization and protein semisynthesis, with the latter illustrated through the modification of native cellular chromatin. The promiscuous inteins reported here thus improve the applicability of existing PTS methods and should enable future efforts to engineer promiscuity into other naturally split inteins.
Deep Private-Feature Extraction (2018)

We present and evaluate Deep Private-Feature Extractor (DPFE), a deep model which is trained and evaluated based on information theoretic constraints. Using the selective exchange of information between a user's device and a service provider, DPFE enables the user to prevent certain sensitive information from being shared with a service provider, while allowing them to extract approved information using their model. We introduce and utilize the log-rank privacy, a novel measure to assess the effectiveness of DPFE in removing sensitive information and compare different models based on their accuracy-privacy trade-off. We then implement and evaluate the performance of DPFEon smartphones to understand its complexity, resource demands, and efficiency trade-offs. Our results on benchmark image datasets demonstrate that under moderate resource utilization, DPFE can achieve high accuracy for primary tasks while preserving the privacy of sensitive information.
An intermediate representation for speculative optimizations in a dynamic compiler (2013)

We present a compiler intermediate representation (IR) that allows dynamic speculative optimizations for high-level languages. The IR is graph-based and contains nodes fixed to control flow as well as floating nodes. Side-effecting nodes include a framestate that maps values back to the original program. Guard nodes dynamically check assumptions and, on failure, deoptimize to the interpreter that continues execution. Guards implicitly use the framestate and program position of the last side-effecting node. Therefore, they can be represented as freely floating nodes in the IR. Exception edges are modeled as explicit control flow and are subject to full optimization. We use profiling and deoptimization to speculatively reduce the number of such edges. The IR is the core of a just-in-time compiler that is integrated with the Java HotSpot VM. We evaluate the design decisions of the IR using major Java benchmark suites.
Principles and Techniques of Biochemistry and Molecular Biology (2005)

This is a new and expanded edition of the bestselling Principles and Techniques of Practical Biochemistry. It includes discussion of the theoretical principles, practical details and applications of the key experimental techniques that are routinely used in modern biochemistry and molecular biology, including those that have led to the emergence of the new disciplines of genomics, proteomics and bioinformatics. All chapters have been updated and new sections added to cover the principles of experimental design, the statistical analysis of quantitative analytical data, and the principles and practice of clinical biochemistry. here are new chapters covering cell culture, microscopy and mass spectrometry. To enhance student understanding of each topic, in-text worked examples are included in each chapter. The textbook will be essential reading for all bioscience students and pre-clinical medical students.
Flow cytometry distinction between adherent and phagocytized yeast particles (1994)

Our laboratory recently developed a light microscopy staining technique that provides a mean to distinguish between yeast that are simply bound to the surface of macrophages and yeast that have actually been phagocytized by macrophages (7). We adapted this technique by using fluorescent probes in order to test phagocytic activity by flow cytometry. Thus we are able to distinguish unambiguously extracellular from intracellular yeast during phagocytosis with the fast rate of flow cytometry (approximately 200 cells/s). The fluorescence quenching induced by a 1% tannic acid solution (w/v) can be applied to any FITC-labeled, heat-killed yeast cell or bacteria. The yeast cells already engulfed in the macrophage remain with their native fluorescence (internal and external pH equilibrated by 50 microM monensin 30 min/4 degrees C) protected from the action of tannic acid, a nonmembrane permeable molecule. The results presented here validate this new technique. An application is presented showing the inhibition of endocytosis by cytochalasin-B.
Process verification of two-qubit quantum gates by randomized benchmarking (2013)

We implement a complete randomized benchmarking protocol on a system of two superconducting qubits. The protocol consists of randomizing over gates in the Clifford group, which experimentally are generated via an improved two-qubit cross-resonance gate implementation and single-qubit unitaries. From this we extract an optimal average error per Clifford operation of $0.0936$. We also perform an interleaved experiment, alternating our optimal two-qubit gate with random two-qubit Clifford gates, to obtain a two-qubit gate error of $0.0653$. We compare these values with a two-qubit gate error of $\ensuremath{\sim}0.12$ obtained from quantum process tomography, which is likely limited by state preparation and measurement errors.
High density lipoproteins, but not other lipoproteins, provide a vehicle for sterol transport to bile. (1997)

Unesterified cholesterol (UC) that is taken up by the liver from lipoproteins is rapidly mixed by exchange with liver UC. Thus, it is not possible to quantitate the transport of UC from different lipoproteins into bile using radiolabeled UC. However, plant sterols do not exchange with UC and are secreted in bile with the same kinetics as UC. To compare the contribution to bile of sterols from different lipoproteins, we perfused isolated rat livers with VLDL, LDL, and HDL that were obtained from patients with hereditary phytosterolemia and were rich in plant sterols. After 30-min recirculating perfusions, hepatic concentrations of plant sterols were not different after different lipoproteins were perfused. However, biliary plant sterol secretion was markedly different: with the perfusion of either VLDL or LDL there was no increase in plant sterols in bile, but with perfusion of HDL, the secretion of plant sterols was increased two- to threefold (P = 0.0005). The increase in biliary plant sterols was detected 5-10 min after HDL was added to perfusates and was similarly large for each of three individual plant sterols that was tracked. Results show that when sterol transport from lipoproteins into bile can be determined, only HDL provides a vehicle for UC elimination in bile that is consistent with its putative function in reverse cholesterol transport.
Arabidopsis ABA Response Gene ABI1 : Features of a Calcium-Modulated Protein Phosphatase (1994)

The Arabidopsis ABI1 locus is essential for a wide spectrum of abscisic acid (ABA) responses throughout plant development. Here, ABI1 was shown to regulate stomatal aperture in leaves and mitotic activity in root meristems. The ABI1 gene was cloned and predicted to encode a signaling protein. Although its carboxyl-terminal domain is related to serine-threonine phosphatase 2C, the ABI1 protein has a unique amino-terminal extension containing an EF hand calcium-binding site. These results suggest that the ABI1 protein is a Ca(2+)-modulated phosphatase and functions to integrate ABA and Ca2+ signals with phosphorylation-dependent response pathways.
A new concept in maxillary implant surgery: the osteotome technique. (1994)

This article reviews the limitations of drilling into soft bone to place endosseous implants. Differences among bone types and the anatomy of the maxilla are described. The osteotome technique, which is a new method of placing implants into maxillary bone without drilling, and the rationale for two other procedures, the osteotome sinus floor elevation and the ridge expansion osteotomy, are detailed. How osteotomes conserve osseous tissue and may improve bone density around the implant is also discussed. A pilot study that shows excellent results with several types of press-fit implants using the osteotome technique is provided. The author concludes that the osteotome technique is superior to drilling for many applications in soft maxillary bone. Furthermore, the osteotome technique allows more implants to be inserted in a greater variety of sites during a routine office procedure.
Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients (2002)

Current theories of CF pathogenesis predict different predisposing “local environmental” conditions and sites of bacterial infection within CF airways. Here we show that, in CF patients with established lung disease, Psuedomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In vitro studies revealed that CF-specific increases in epithelial O2 consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate production. With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted. These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments.
Brain tissue reaction to permselective polymer capsules (1989)

The brain tissue reaction to permselective polymer capsules implanted in rats was evaluated for 1 to 54 weeks. The polymer capsules were well tolerated in all animals and no recognizable neurological or behavioral deficits were associated with the implants. Necrosis at the brain/polymer interface, as assessed with Nissl stain, was not observed. Foreign body giant cells were consistently absent. Immunocytochemically identified reactive neuroglial cells showed a remarkably low-grade tissue response to the synthetic material beyond the first 2 weeks of observation. Immunolabeled cortical neurons revealed conserved columnar arrays around the implants. Transmission electron microscopy showed a minimal degree of collagen deposition compared to implants in peripheral sites, and normal synapses within a few micrometers from the brain/polymer interface, supporting the prospect of biocompatible, immunoisolated xenografts in the central nervous system.
A nitric oxide agonist stimulates consolidation of long-term memory in the 1-day-old chick. (1994)

Chicks, age 1 to 2 days, that have been trained on a passive avoidance task with a strongly reinforced training trial yield a memory trace that is composed of 3 behaviorally and pharmacologically distinguishable stages, with the final long-term memory stage being dependent on protein synthesis. In contrast, chicks trained with a weakly reinforced learning trial typically do not demonstrate this final stage of memory. Sodium nitroprusside 150 microM intracranially administered immediately after a weak training trial promoted the formation of long-term memory, whereas saline did not. The results suggest that nitric oxide synthesis is either itself critical or stimulates other processes that are critical for the consolidation of long-term memory.
Evidence-Based Medicine and Clinical Research: Both Are Needed, Neither Is Perfect (2018)

Currently, it is impossible to think of modern healthcare that ignores evidence-based medicine (EBM), a concept which relies on 3 pillars: individual clinical expertise, the values and desires of the patient, and the best available research. However, EBM is not perfect. Clinical research is also far from being perfect. This article provides an overview of the basic principles, opportunities, and controversies offered by EBM. It also summarizes current discussions on clinical research. Potential solutions to the problems of EBM and clinical research are discussed as well. If there were specific issues related to pediatric nutrition, an attempt was made to discuss the basic principles and limitations in this context. However, the conclusions are applicable to EBM and clinical research in general. In the future, considering that new ways of obtaining health data will continue to emerge, the world of EBM and clinical research is likely to change. The ultimate goal, however, will remain the same: improving health outcomes for patients.
Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells (2003)

The retinoid X receptor (RXR) is essential as a common heterodimerization partner of several nuclear receptors (NRs). However, its function as a bona fide receptor for endogenous ligands has remained poorly understood. Such a role would depend on the existence of RXR activating ligands in vivo and on the ability of such ligands to influence relevant biological functions. Here we demonstrate the presence of endogenous RXR ligands in the embryonic central nervous system (CNS) and show that they can activate heterodimers formed between RXR and the orphan NR Nurr1 in vivo. Moreover, RXR ligands increase the number of surviving dopaminergic cells and other neurons in a process mediated by Nurr1-RXR heterodimers. These results provide evidence for a role of Nurr1 as a ligand-independent partner of RXR in its function as a bona fide ligand-activated NR. Finally, our findings identify RXR-Nurr1 heterodimers as a potential target in the treatment of neurodegenerative disease.
Transduction of Redox Signaling by Electrophile-Protein Reactions (2009)

Over the last 50 years, the posttranslational modification (PTM) of proteins has emerged as a central mechanism for cells to regulate metabolism, growth, differentiation, cell-cell interactions, and immune responses. By influencing protein structure and function, PTM leads to a multiplication of proteome diversity. Redox-dependent PTMs, mediated by environmental and endogenously generated reactive species, induce cell signaling responses and can have toxic effects in organisms. PTMs induced by the electrophilic by-products of redox reactions most frequently occur at protein thiols; other nucleophilic amino acids serve as less favorable targets. Advances in mass spectrometry and affinity-chemistry strategies have improved the detection of electrophile-induced protein modifications both in vitro and in vivo and have revealed a high degree of amino acid and protein selectivity of electrophilic PTM. The identification of biological targets of electrophiles has motivated further study of the functional impact of various PTM reactions on specific signaling pathways and how this might affect organisms.
Testing Carbon‐Coated VOx Prepared via Reaction under Autogenic Pressure at Elevated Temperature as Li‐Insertion Materials (2006)

V2O3 nanoparticles covered by a 15 nm thick uniform carbon coating are prepared by reaction under autogenic pressure at elevated temperature of VO(OC2H5)3 at 700 °C. Further oxidation of this material produces carbon-coated V2O5 nanoparticles. Both materials reversibly insert Li (see figure) electrochemically in nonaqueous Li-salt solutions.