gebhart/patrepeval huggingface dataset:
Efficient Intracellular Assembly of Papillomaviral Vectors (2003)

Although the papillomavirus structural proteins, L1 and L2, can spontaneously coassemble to form virus-like particles, currently available methods for production of L1/L2 particles capable of transducing reporter plasmids into mammalian cells are technically demanding and relatively low-yield. In this report, we describe a simple 293 cell transfection method for efficient intracellular production of papillomaviral-based gene transfer vectors carrying reporter plasmids. Using bovine papillomavirus type 1 (BPV1) and human papillomavirus type 16 as model papillomaviruses, we have developed a system for producing papillomaviral vector stocks with titers of several billion transducing units per milliliter. Production of these vectors requires both L1 and L2, and transduction can be prevented by papillomavirus-neutralizing antibodies. The stocks can be purified by an iodixanol (OptiPrep) gradient centrifugation procedure that is substantially more effective than standard cesium chloride gradient purification. Although earlier data had suggested a potential role for the viral early protein E2, we found that E2 protein expression did not enhance the intracellular production of BPV1 vectors. It was also possible to encapsidate reporter plasmids devoid of BPV1 DNA sequences. BPV1 vector production efficiency was significantly influenced by the size of the target plasmid being packaged. Use of 6-kb target plasmids resulted in BPV1 vector yields that were higher than those with target plasmids closer to the native 7.9-kb size of papillomavirus genomes. The results suggest that the intracellular assembly of papillomavirus structural proteins around heterologous reporter plasmids is surprisingly promiscuous and may be driven primarily by a size discrimination mechanism.
Hierarchical and distributed information handling for UPT (1990)

Various types of personal telecommunications (PT) services are summarized, and the service information required to provide them are identified. Information-allocation schemes over multiple networks are examined. Hierarchical information-handling and information-localization schemes and their applicability to PT services are discussed. The effects of hierarchical information handling and information localization are discussed in the framework of the intelligent network.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Immunoregulation of Dendritic Cells (2005)

The paradigm of tolerogenic/immature versus inflammatory/mature dendritic cells has dominated the recent literature regarding the role of these antigen-presenting cells in mediating immune homeostasis or self-tolerance and response to pathogens, respectively. This issue is further complicated by the identification of distinct subtypes of dendritic cells that exhibit different antigen-presenting cell effector functions. The discovery of pathogen-associated molecular patterns and toll-like receptors provides the mechanistic basis for dendritic cell recognition of specific pathogens and induction of appropriate innate and adaptive immune responses. Only recently has insight been gained into how dendritic cells contribute to establishing and/or maintaining immunological tolerance to self. Soluble and cellular mediators have been reported to effectively regulate the function of dendritic cells by inducing several outcomes ranging from non-inflammatory dendritic cells that lack the ability to induce T lymphocyte activation to dendritic cells that actively suppress T lymphocyte responses. A thorough discussion of these stimuli and their outcomes is essential to understanding the potential for modulating dendritic cell function in the treatment of inflammatory disease conditions.
An analytic reflection method for time-domain fluorescence diffuse optical tomography based on a generalized pulse spectrum technique (2008)

An image reconstruction scheme for time-domain fluorescence diffuse optical tomography is proposed using a reflection-mode for a semi-infinite turbid geometry. The method is based on a generalized pulse spectrum technique that employs analytic expressions of the Laplace-transformed time-domain photon-diffusion model to construct a Born normalized inverse model, and a pair of real domain transform-factors to separate distributions of the fluorescent yield and lifetime. The methodology is validated with a specifically-developed fluorescent Monte-Carlo simulator or finite-element-based methods and its robustness to the background uncertainties is investigated.
Trimethoprim and rifampicin: in vitro activities separately and in combination (1975)

Journal Article Trimethoprim and rifampicin: in vitro activities separately and in combination Get access D. W. Kerry, D. W. Kerry Department of Medical MicrobiologyThe Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, England Search for other works by this author on: Oxford Academic PubMed Google Scholar J. M. T. Hamilton-Miller, J. M. T. Hamilton-Miller Department of Medical MicrobiologyThe Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, England Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Brumfitt W. Brumfitt Department of Medical MicrobiologyThe Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, England Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 1, Issue 4, December 1975, Pages 417–427, https://doi.org/10.1093/jac/1.4.417 Published: 01 December 1975 Article history Accepted: 30 July 1975 Published: 01 December 1975
Conditional okay for cannabis prescription drug (2005)

Health Canada has conditionally approved the first cannabis-derived prescription pain killer. Cannabis sativa extract (Sativex), an under-the-tongue spray, was approved in April for use as an adjunctive treatment for the symptom relief of neuropathic pain in patients with multiple sclerosis (MS).
Solid supported hydrolysis of apurinic sites in synthetic oligonudeotides for rapid and efficient purification on reverse-phase cartridges (1988)

Rapid purification methods for synthetic oligonucleotides involving reverse-phase cartridges (RPC) and enzymatic hydrolysis have been introduced. These methods are based on a discrimination between the desired target fragment protected with a 5'-DMT group and incompletely elongated products possessing a 5'-hydroxyl function. For target products over 60 nucleotides, the rapid methods are of little use as reported to date. We have found that the problem is due to the presence of truncated 5'-DMT fragments generated from apurinic sites within the target product during NH4OH deprotection. These side products are co-purified with the target fragment when the rapid purification procedures are employed. If a step is included during deprotection to cleave the apurinic sites prior to removal of the crude product from the solid support (1 M lysine-HCl, pH 9 for 90 min at 60 degrees C), fragments up to 118 bases can be purified by RPC to near homogeneity.
Gene expression during leaf senescence (1994)

Leaf senescence is a hiphly-controlled sequence of events comprising the final stage of development. Cells remain viable during the process and new gene expression is required. There is some similarity between senescence in plants and programmed cell death in animals. In this review, different classes of senescence-related genes are defined and progress towards isolating such genes is reported. A range of internal and external factors which appear to cause leaf senescence is considered and various models for the mechanism of senescence- initiation are described. The current understanding of senescence at the wrganelle and molecular levels is presented. Finally, same ideas are mooted as to why senescence occurs and why it should be studied further. Contents Summary 419 I. Introduction 420 II. Internal factors that cause senescence 423 III. External factors that cause senescence 427 IV. What is the mechanism of senescence initiation? 428 V. Progress in the understanding of organelle senescence 431 VI. Progress in the understanding of senescence at the molecular level 434 VII. The control of senescence in animals and plants 440 VIII. Why is senescence necessary? 441 IX. Why study senescence? 441 References 442.
Ketamine in Chronic Pain Management: An Evidence-Based Review (2003)

Ketamine has diverse effects that may be of relevance to chronic pain including: N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, gamma-aminobutyric acid(A) receptors; inhibition of voltage gated Na(+) and K(+) channels and serotonin, dopamine re-uptake. Ketamine has been in clinical practice for over 30 yr; however, there has been little formal research on the effectiveness of ketamine for chronic pain management. In this review we evaluate the available clinical data as a basis for defining the potential use of ketamine for chronic pain. Literature referenced in this review was obtained from a computer search of EMBASE and MEDLINE from 1966 through August, 2002. Search terms included ketamine, ketalar, pain, painful, analgesic, and analgesia. Abstracts were screened for relevance and publications relating to chronic pain use were obtained. Levels of evidence were stratified according to accepted guidelines (level I-IV). For central pain, there is level II and level IV evidence of efficacy for parenteral and oral ketamine. For complex regional pain syndromes, there is only level IV evidence of efficacy of epidural ketamine. For fibromyalgia, there is level II evidence of pain relief, reduced tenderness at trigger points, and increased endurance. For ischemic pain, a level II study reported a potent dose-dependent analgesic effect, but with a narrow therapeutic window. For nonspecific neuropathic pain, level II and level IV studies reported divergent results with questionable long-term effects on pain. For phantom limb pain and postherpetic neuralgia, level II and level II studies provided objective evidence of reduced hyperpathia and pain relief was usually substantial either after parenteral or oral ketamine. Acute on chronic episodes of severe neuropathic pain represented the most frequent use of ketamine as a "third line analgesic," often by IV or subcutaneous infusion (level IV). In conclusion, the evidence for efficacy of ketamine for treatment of chronic pain is moderate to weak. However, in situations where standard analgesic options have failed ketamine is a reasonable "third line" option. Further controlled studies are needed.
Oxidative dna Damage of Lymphocytes in Peripheral Blood and Ascites in Cancer Patients (2012)

Results indicate the presence of significant oxidative damage to the dna of lymphocytes in peripheral blood and ascites from patients with ma, being especially higher in the cells from ascites. The lower tac of ma supernatant may be related to a higher degree of dna damage to tals. The present study suggests that an oxidant-antioxidant imbalance may be one of the mechanisms leading to the dna damage detected in peripheral blood and local tals in patients with ma, which may provide a novel approach to the treatment of ma.
Utilizing Structures of CYP2D6 and BACE1 Complexes To Reduce Risk of Drug–Drug Interactions with a Novel Series of Centrally Efficacious BACE1 Inhibitors (2015)

In recent years, the first generation of β-secretase (BACE1) inhibitors advanced into clinical development for the treatment of Alzheimer's disease (AD). However, the alignment of drug-like properties and selectivity remains a major challenge. Herein, we describe the discovery of a novel class of potent, low clearance, CNS penetrant BACE1 inhibitors represented by thioamidine 5. Further profiling suggested that a high fraction of the metabolism (>95%) was due to CYP2D6, increasing the potential risk for victim-based drug-drug interactions (DDI) and variable exposure in the clinic due to the polymorphic nature of this enzyme. To guide future design, we solved crystal structures of CYP2D6 complexes with substrate 5 and its corresponding metabolic product pyrazole 6, which provided insight into the binding mode and movements between substrate/inhibitor complexes. Guided by the BACE1 and CYP2D6 crystal structures, we designed and synthesized analogues with reduced risk for DDI, central efficacy, and improved hERG therapeutic margins.
Viability of the free newspaper business model (2008)

Data HK 2026 hasil undian angka togel Hongkong pools melalui keluaran HK prize dan pengeluaran HK dari siaran langsung live HK yang disusun dalam Tabel untuk menampilkan hasil result HK dalam putaran togel hari ini.
Using Your Beam Efficiently: Reducing Electron Dose in the STEM via Flyback Compensation (2022)

Abstract In the scanning transmission electron microscope, fast-scanning and frame-averaging are two widely used approaches for reducing electron-beam damage and increasing image signal noise ratio which require no additional specialized hardware. Unfortunately, for scans with short pixel dwell-times (less than 5 μs), line flyback time represents an increasingly wasteful overhead. Although beam exposure during flyback causes damage while yielding no useful information, scan coil hysteresis means that eliminating it entirely leads to unacceptably distorted images. In this work, we reduce this flyback to an absolute minimum by calibrating and correcting for this hysteresis in postprocessing. Substantial improvements in dose efficiency can be realized (up to 20%), while crystallographic and spatial fidelity is maintained for displacement/strain measurement.
Improved glucose tolerance by acute vanadate but not by selenate exposure in genetically obese rats (fa/fa). (1995)

The results demonstrate improved glucose tolerance and decreased plasma insulin concentration during acute vanadate exposure. Only a transient insulinotropic effect with improved glucose tolerance is induced during acute selenate exposure, and is followed by progressive development of hyperglycemia indicating selenate toxicity.
Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. (1993)

Two classes of sequences in the yeast Saccharomyces cerevisiae are subject to transcriptional silencing: the silent mating-type cassettes and telomeres. In this report we demonstrate that the silencing of these regions is strictly associated with acetylation of the epsilon-amino groups of lysines in the amino-terminal domains of three of the four core histones. Both the silent mating-type cassettes and the Y domains of telomeres are packaged in nucleosomes in vivo that are hypoacetylated relative to those packaging active genes. This difference in acetylation is eliminated by genetic inactivation of silencing: The silent cassettes from sir2, sir3, or sir4 cells show the same level of acetylation as other active genes. The correspondence of silencing and hypoacetylation of the mating-type cassettes is observed even for an allele lacking a promoter, indicating that silencing per se, rather than the absence of transcription, is correlated with hypoacetylation. Finally, overexpression of Sir2p, a protein required for transcriptional silencing in yeast, yields substantial histone deacetylation in vivo. These studies fortify the hypothesis that silencing in yeast results from heterochromatin formation and argue that the silencing proteins participate in this formation.
Human cathepsin H (1980)

Cathepsin H was purified from human liver by a method involving autolysis and acetone fractionation, and chromatography on DEAE-cellulose, Ultrogel AcA 54, hydroxyapatite and concanavalin A-Sepharose. The procedure allowed for the simultaneous isolation of cathepsin B and cathepsin D. Cathepsin H was shown to consist of a single polypeptide chain of 28 000 mol.wt., and affinity for concanavalin A-Sepharose indicated that it was a glycoprotein. The enzyme existed in multiple isoelectric forms, the two major forms having pI values of 6.0 and 6.4; it hydrolysed azocasein (pH optimum 5.5), benzoylarginine 2-naphthylamide (Ba-Arg-NNap), leucyl 2-naphthylamide (Arg-NNap), (pH optimum 6.8). Arg-NNap and Arg-NMec, unlike Bz-Arg-NNap-, were not hydrolysed by human cathepsin B. Cathepsin H was similar to cathepsin B in being irreversibly inactivated by exposure to alkaline pH. Sensitivity to chemical inhibitors by 1 microM-leupeptin, which gave essentially complete inhibition of the other lysosomal cysteine proteinases, cathepsins B and L.
Fluorescence-Enhanced Europium-Diethylenetriaminepentaacetic (DTPA)-Monoamide Complexes for the Assessment of Renal Function (2008)

Real-time, noninvasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we have prepared and evaluated Eu(3+) complexes of several diethylenetriamine pentaacetate (DTPA)-monoamide ligands bearing molecular "antennae" to enhance metal fluorescence via intramolecular ligand-metal fluorescence resonance energy transfer process. The results show that Eu-DTPA-monoamide complex 18b, which contains a quinoxanlinyl antenna, exhibits large (ca. 2700-fold) Eu(3+) fluorescence enhancement. Indeed, complex 18b exhibits the highest fluorescent enhancement observed thus far in the DTPA-type metal complexes. The renal clearance property was assessed using the corresponding radioactive (111)In complex 18a, and the data suggest that this complex clears via a complex mechanism that includes glomerular filtration.
High current density emitter-down InGaAlAs heterojunction bipolar transistors (1989)

The authors discuss the use of deep O/sup +/ ion implantation, in conjunction with multiple self-aligned device geometries, to more efficiently block parasitic injection through the extrinsic base diode and allow much higher current density operation of inverted HBTs (heterojunction bipolar transistors) than would be achieved by standard techniques. In GaAlAs on InP, inverted HBTs were fabricated using several self-aligned as well as standard processes, with the final goal a novel four-mask, triple self-aligned process using semi-insulating substrates. The collector current density for maximum current gain (I/sub max/) has been measured for inverted HBTs of varying emitter stripe width and exhibits a clear inverse proportionality to the stripe width. While maximum current densities of approximately=150 A/cm/sup 2/ were measured for devices of 60- mu m stripe width, values in excess of 1000 A/cm/sup 2/ were measured for a device with a 6- mu m stripe width.
A Common Binding Site Mediates Heterodimerization and Homodimerization of Bcl-2 Family Members (1997)

Bcl-2 inhibits apoptosis induced by a wide variety of stimuli. In contrast, the Bcl-2 homologue, Bax, antagonizes Bcl-2's death protecting function. Bcl-2 forms protein-protein homodimers with itself and heterodimers with Bax, and previous experiments have shown that point mutations in Bcl-2 can abrogate Bax binding while leaving homodimerization intact. These mutagenesis results can be interpreted to suggest that Bcl-2 has separate binding sites that are responsible for homodimer and heterodimer formation. Results from yeast two-hybrid studies have also suggested that homodimerization and heterodimerization reflect distinct modes of interaction. However, using quantitative plate binding assays, we now show that Bax as well as peptides derived from the BH3 domains of Bax and Bak block both Bcl-2/Bax binding and Bcl-2/Bcl-2 binding. Similar assays demonstrate that Bcl-xL can form both homodimers and heterodimers and that these interactions are also inhibited by Bax and the BH3-derived peptides. These results demonstrate that the same binding motifs are responsible for both homodimerization and heterodimerization of Bcl-2 family members.
Uncovering Physiologic Mechanisms of Circadian Rhythms and Sleep/Wake Regulation through Mathematical Modeling (2007)

Mathematical models of neurobehavioral function are useful both for understanding the underlying physiology and for predicting the effects of rest-activity-work schedules and interventions on neurobehavioral function. In a symposium titled "Modeling Human Neurobehavioral Performance I: Uncovering Physiologic Mechanisms" at the 2006 Society for Industrial and Applied Mathematics/Society for Mathematical Biology (SIAM/SMB) Conference on the Life Sciences, different approaches to modeling the physiology of human circadian rhythms, sleep, and neurobehavioral performance and their usefulness in understanding the underlying physiology were examined. The topics included key elements of the physiology that should be included in mathematical models, a computational model developed within a cognitive architecture that has begun to include the effects of extended wake on information-processing mechanisms that influence neurobehavioral function, how to deal with interindividual differences in the prediction of neurobehavioral function, the applications of systems biology and control theory to the study of circadian rhythms, and comparisons of these methods in approaching the overarching questions of the underlying physiology and mathematical models of circadian rhythms and neurobehavioral function. A unifying theme was that it is important to have strong collaborative ties between experimental investigators and mathematical modelers, both for the design and conduct of experiments and for continued development of the models.
The periplasmic serine protease inhibitor ecotin protects bacteria against neutrophil elastase (2004)

Ecotin is a dimeric periplasmic protein from Escherichia coli that has been shown to inhibit potently many trypsin-fold serine proteases of widely varying substrate specificity. To help elucidate the physiological function of ecotin, we examined the family of ecotin orthologues, which are present in a subset of Gram-negative bacteria. Phylogenetic analysis suggested that ecotin has an exogenous target, possibly neutrophil elastase. Recombinant protein was expressed and purified from E. coli, Yersinia pestis and Pseudomonas aeruginosa, all species that encounter the mammalian immune system, and also from the plant pathogen Pantoea citrea. Notably, the Pa. citrea variant inhibits neutrophil elastase 1000-fold less potently than the other orthologues. All four orthologues are dimeric proteins that potently inhibit (<10 pM) the pancreatic digestive proteases trypsin and chymotrypsin, while showing more variable inhibition (5 pM to 24 microM) of the blood proteases Factor Xa, thrombin and urokinase-type plasminogen activator. To test whether ecotin does, in fact, protect bacteria from neutrophil elastase, an ecotin-deficient strain was generated in E. coli. This strain is significantly more sensitive in cell-killing assays to human neutrophil elastase, which causes increased permeability of the outer membrane that persists even during renewed bacterial growth. Ecotin affects primarily the ability of E. coli to recover and grow following treatment with neutrophil elastase, rather than the actual rate of killing. This suggests that an important part of the antimicrobial mechanism of neutrophil elastase may be a periplasmic bacteriostatic effect of protease that has translocated across the damaged outer membrane.