gebhart/patrepeval huggingface dataset:
Safety, tolerability and pharmacokinetics of subcutaneous Å6, an 8-amino acid peptide with anti-angiogenic properties, in healthy men (2004)

Single doses of A6 up to 300 mg, and repeated doses up to 150 mg, were well-tolerated and safe in healthy young men. A6 was rapidly absorbed; it was eliminated, mainly unchanged, in urine. Plasma concentrations were dose-proportional. A6 did not trigger an early immunogenic response.
Heme Binding and Transport—A Spectrophotometric Study of Plasma Glycoglobulin Hemochromogens (1971)

A hitherto unreported phenomenon is the immediate production of the spectrum of ferrohemochromogens (in the presence of sodium dithionite) upon the addition in vitro of hydroxyhemin (pH 7.6-7.8) to the plasmas or sera, as well as to certain Cohn plasma protein fractions, of all mammalian species thus far examined. This distinctive reaction is characteristic of a coordination complex with heme iron, and is ascribed to a remarkable affinity for heme of certain plasma glycoglobulins, which include hemopexin. Spectrophotometry has permitted estimations of the specific heme-binding capacity (as ferrohemochromogen) of the plasmas, the rate of removal from plasma of injected heme, and the production of bile pigments therefrom. The study leads to a new proposal of the cooperative roles of the glycoglobulin hemochromogens and hematin-albumin in heme transport and bile pigment production.
The promoter of the gene encoding 3',5'-cyclic adenosine monophosphate (cAMP) response element binding protein contains cAMP response elements: evidence for positive autoregulation of gene transcription (1993)

The transcriptional transactivational activities of the phosphoprotein cAMP-response element-binding protein (CREB) are activated by the cAMP-dependent protein kinase A signaling pathway. Dimers of CREB bind to the palindromic DNA element 5'-TGACGTCA-3' (or similar motifs) called cAMP-responsive enhancers (CREs) found in the control regions of many genes, and activate transcription in response to phosphorylation of CREB by protein kinase A. Earlier we reported on the cyclical expression of the CREB gene in the Sertoli cells of the rat testis that occurred concomitant with the FSH-induced rise in cellular cAMP levels and suggested that transcription of the CREB gene may be autoregulated by cAMP-dependent transcriptional proteins. We now report the structure of the 5'-flanking sequence of the human CREB gene containing promoter activity. The promoter has a high content of guanosines and cytosines and lacks canonical TATA and CCAAT boxes typically found in the promoters of genes in eukaryotes. Notably, the promoter contains three CREs and transcriptional activities of a promoter-luciferase reporter plasmid transfected to placental JEG-3 cells are increased 3- to 5-fold over basal activities in response to either cAMP or 12-O-tetradecanoyl phorbol-14-acetate, and give 6- to 7-fold responses when both agents are added. The CREs bind recombinant CREB and endogenous CREB or CREB-like proteins contained in placental JEG-3 cells and also confer cAMP-inducible transcriptional activation to a heterologous minimal promoter. Our studies suggest that the expression of the CREB gene is positively autoregulated in trans.
Time course of change in ventilatory response to CO2 with long-term CPAP therapy for obstructive sleep apnea. (1987)

Nineteen subjects with the obstructive sleep apnea syndrome (10 with daytime arterial CO2 tension 44 mm Hg or higher) were treated with long-term nocturnal continuous positive airway pressure. The ventilatory response to CO2 (Read's method) was measured in triplicate prior to treatment and after 1, 2, 3, 7, and 14 or more nights of therapy. Seven subjects were tested on at least 4 occasions. For each test, slope of the response line and position of the response line (ventilation at a PCO2 of 60 mm Hg) were calculated. The subjects with initial high daytime CO2 showed no change in slope of response with treatment but showed a progressive increase in ventilation at any given degree of PCO2. Ventilation at a PCO2 of 60 mm Hg increased from a mean of 20.0 +/- 1.3 SEM L/min by 8.0 +/- 2.5 SEM L/min after 2 nights of therapy (p less than 0.05, two-way analysis of variance), and by 16.2 +/- 1.9 L/min after 2 wk or more (p less than 0.01). On average, there was no significant change in either slope or position of response in the subjects with initially normal daytime PCO2. We conclude that airway obstruction in sleep (in obstructive sleep apnea syndrome) leads in some subjects to respiratory failure in the daytime, with a left shift in the ventilatory response to CO2, and that this changes is usually reversible during the next several days.
Eph B4 Receptor Signaling Mediates Endothelial Cell Migration and Proliferation via the Phosphatidylinositol 3-Kinase Pathway (2002)

The goals of this study were 2-fold: 1) to determine whether stimulation of Eph B4 receptors promotes microvascular endothelial cell migration and/or proliferation, and 2) to elucidate signaling pathways involved in these responses. The human endothelial cells used possessed abundant Eph B4 receptors with no endogenous ephrin B2 expression. Stimulation of these receptors with ephrin B2/Fc chimera resulted in dose- and time-dependent phosphorylation of Akt. These responses were inhibited by LY294002 and ML-9, blockers of phosphatidylinositol 3-kinase (PI3K) and Akt, respectively. Eph B4 receptor activation increased proliferation by 38%, which was prevented by prior blockade with LY294002, ML-9, and inhibitors of protein kinase G (KT5823) and MEK (PD98059). Nitrite levels increased over 170% after Eph B4 stimulation, indicating increased nitric oxide production. Signaling of endothelial cell proliferation appears to be mediated by a PI3K/Akt/endothelial nitric-oxide synthase/protein kinase G/mitogen-activated protein kinase cascade. Stimulation with ephrin B2 also increased migration by 63% versus controls. This effect was inhibited by blockade with PP2 (Src inhibitor), LY294002 or ML-9 but was unaffected by the PKG and MEK blockers. Eph B4 receptor stimulation increased activation of both matrix metalloproteinase-2 and -9. The results from these studies indicate that Eph B4 stimulates migration and proliferation and may play a role in angiogenesis.
selection of Cancer Chemotherapy for a Patient by an In Vitro Assay Versus a Clinician (1990)

One hundred thirty-three patients with advanced metastatic cancer were randomized to receive single-agent chemotherapy selected by either a medical oncologist or an in vitro capillary cloning system. Thirty-six of the 65 patients (55%) who were randomly assigned to selection of a drug by the clinician actually received a drug; these patients were able to be evaluated for clinical response. Of these 36 patients, one had a partial tumor response (3%). Only 19 of the 68 patients (28%) who were randomly assigned to selection of a drug by the capillary system actually received a drug; these patients were able to be evaluated for clinical response. Of these 19 patients, four (21%) had partial tumor responses. In the assessable patients (36 in the clinician's choice group, 19 in the capillary cloning group), the partial response rate was superior for drug selection by the capillary cloning system (P = .04). For all patients randomly assigned to a group (65 in the clinician's choice group, 68 in the capillary cloning group), the response rate was not significantly different (1.5% and 5.9%, respectively; P = .37). When overall survival rates for patients in the two groups were compared, there was no difference. We conclude that drug sensitivity testing in capillary tubes can improve the response rate for patients with advanced malignancies. This improved response rate, however, does not translate into improved survival times for these patients.
Optical coherence tomography of the suprachoroid after CyPass Micro-Stent implantation for the treatment of open-angle glaucoma (2013)

OCT imaging provides adequate visualisation of the angle, the SCS and aqueous fluid drainage after implantation of a suprachoroidal microstent into the SCS.
The effect of direct-reverse pulse parameters on the morphology & corrosion resistance of nickel deposits (2001)

When electrodeposited nickel is used in the corrosion protection of steel, two factors are important: the porosity and corrosion resistance of the coating. The optimum direct-reverse pulse parameters of nickel deposits were determined using factorial experiments. Compared to direct current plating, electrodeposition of nickel using pulse plating can provide coatings with lower porosity and improved corrosion resistance. The reason for this is found in the distinct changes in texture and crystallite size as measured by XRD and SEM studies.
Black silicon method: X. A review on high speed and selective plasma etching of silicon with profile control: an in-depth comparison between Bosch and cryostat DRIE processes as a roadmap to next generation equipment (2009)

An intensive study has been performed to understand and tune deep reactive ion etch (DRIE) processes for optimum results with respect to the silicon etch rate, etch profile and mask etch selectivity (in order of priority) using state-of-the-art dual power source DRIE equipment. The research compares pulsed-mode DRIE processes (e.g. Bosch technique) and mixed-mode DRIE processes (e.g. cryostat technique). In both techniques, an inhibitor is added to fluorine-based plasma to achieve directional etching, which is formed out of an oxide-forming (O2) or a fluorocarbon (FC) gas (C4F8 or CHF3). The inhibitor can be introduced together with the etch gas, which is named a mixed-mode DRIE process, or the inhibitor can be added in a time-multiplexed manner, which will be termed a pulsed-mode DRIE process. Next, the most convenient mode of operation found in this study is highlighted including some remarks to ensure proper etching (i.e. step synchronization in pulsed-mode operation and heat control of the wafer). First of all, for the fabrication ...... Enjoy reading . Henri Jansen 18 June 2008
Functionally biased signalling properties of7TMreceptors – opportunities for drug development for the ghrelin receptor (2013)

This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7.
Salivary antioxidants and periodontal disease status (2002)

Periodontal disease is a common chronic adult condition. The bacterium Porphyromonas gingivalis has been implicated in the aetiology of this disease, which causes destruction of the connective tissue and bone around the root area of the tooth. It has been observed that invading P. gingivalis bacteria trigger the release of cytokines such as interleukin 8 and tumour necrosis factor a, leading to elevated numbers and activity of polymorphonucleocytes (PMN). As a result of stimulation by bacterial antigens, PMN produce the reactive oxygen species (ROS) superoxide via the respiratory burst as part of the host response to infection. Patients with periodontal disease display increased PMN number and activity. It has been suggested that this proliferation results in a high degree of ROS release, culminating in heightened oxidative damage to gingival tissue, periodontal ligament and alveolar bone. Antioxidant constituents in plasma have been well-documented, being chiefly ascorbate, albumin and urate, and these are known to display sensitivity to dietary antioxidant intakes. The concentration of antioxidants in saliva does not appear to mirror those of plasma. The extent of dietary influence upon salivary antioxidant status is unclear. Urate is the predominant salivary antioxidant, with albumin and ascorbate providing minor contributions. Previous research has found reduced salivary antioxidant activity in patients suffering from periodontal disease. An improved understanding of the role antioxidants play in periodontitis, and the influence of nutrition on antioxidant status, may lead to a possible nutritional strategy for the treatment of periodontal disease.
Novel Stilbenes as Probes for Amyloid Plaques (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNovel Stilbenes as Probes for Amyloid PlaquesHank F. Kung, Chi-Wan Lee, Zhi-Ping Zhuang, Mei-Ping Kung, Catherine Hou, and Karl PlösslView Author Information Departments of Radiology and Pharmacology University of Pennsylvania, Room 305 3700 Market Street, Philadelphia, Pennsylvania 19104 Cite this: J. Am. Chem. Soc. 2001, 123, 50, 12740–12741Publication Date (Web):November 21, 2001Publication History Received26 July 2001Published online21 November 2001Published inissue 19 December 2001https://doi.org/10.1021/ja0167147Copyright © 2001 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1481Altmetric-Citations148LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (31 KB) Get e-AlertsSupporting Info (4)»Supporting Information Supporting Information SUBJECTS:Central nervous system,Peptides and proteins,Probes,Reaction products,Screening assays Get e-Alerts
Syntheses of some azinylhydroxylamines (1979)

Abstract Syntheses of some hydroxylaminoazines and hydroxamic acids were investigated. For direct displacement with hydroxylamine a good leaving group, activated by other substituents, must be present.
A Method for Determining the Penetration of Reducing Agents into Wool Using Fluorescence Microscopy (1989)

The fluorogenic reagent 4-(aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (ABD- F) has been used to label thiol groups in partially reduced wool fibers. In fibers in which 10% of the disulfide bonds were reduced with either dithiothreitol or tributyl phosphine, up to 66% of the thiol groups were specifically labeled in 2 hours at pH 8. The extent of the labeling was determined by analysis of ABD-labeled wool for cysteine- S-ABD. Specificity of labeling was confirmed by comparing the amino acid analyses of untreated wool with reduced wool before and after treatment with ABD-F. Fibers were reduced with a variety of reducing agents, and sections were examined by fluo rescence microscopy. From the distribution of the fluorescence. reduction was largely confined to the outer regions of the fiber for 10% reduction at pH 9 (40°C, 30 minutes) with dithiothreitol, tributylphosphine, and tetrakis(hydroxymethyl)-phosphonium chloride. With sodium thioglycollate, however, there was more even penetration of the fibers under the same conditions. The application of this method is discussed for assessing the effect of reducing agents used in conjunction with polymer shrink-resist treatments.
Methyl 2-((Succinimidooxy)carbonyl)benzoate (MSB):  A New, Efficient Reagent forN-Phthaloylation of Amino Acid and Peptide Derivatives (2002)

A new, efficient, and readily available reagent, methyl 2-((succinimidooxy)carbonyl)benzoate (MSB), for N-phthaloylation of amino acids and amino acid derivatives is described. The phthaloylation procedure is simple and racemization-free and gives excellent results with α-amino acids, α-amino alcohols, dipeptides, α-amino carboxamides, and α-amino esters.
In vitro purging of bone marrow for autologous marrow transplantation in acute myelogenous leukemia using myeloid-specific monoclonal antibodies. (1988)

Autologous bone marrow transplantation (ABMT) for acute myelogenous leukemia has gained new popularity recently due to the availability of techniques to purge the autograft of residual leukemia cells. One of the methods of purging involves the use of monoclonal antibodies (mAbs) directed to antigens expressed on the surface of leukemia cells. Several mAbs lend themselves to this use because of their high degree of reactivity with leukemia cells and their lack of reactivity with normal pluripotent hematopoietic progenitor cells. Candidate mAbs include those directed to the CD14, CD15, and CD33 molecules. This review focuses on the pre-clinical data concerning the use of mAbs to these antigens and on the results of on-going clinical trials of ABMT using mAb-mediated purging.
Multi-Axis Bend Sensing Using a Single Surface Relief Fiber Bragg Grating (2006)

We use a single surface relief fiber Bragg grating as a bend sensor with two degrees of freedom. By monitoring the Bragg efficiency and Bragg wavelength, an effective multi-axis bend sensor can be realized.
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data (2010)

Next-generation DNA sequencing (NGS) projects, such as the 1000 Genomes Project, are already revolutionizing our understanding of genetic variation among individuals. However, the massive data sets generated by NGS--the 1000 Genome pilot alone includes nearly five terabases--make writing feature-rich, efficient, and robust analysis tools difficult for even computationally sophisticated individuals. Indeed, many professionals are limited in the scope and the ease with which they can answer scientific questions by the complexity of accessing and manipulating the data produced by these machines. Here, we discuss our Genome Analysis Toolkit (GATK), a structured programming framework designed to ease the development of efficient and robust analysis tools for next-generation DNA sequencers using the functional programming philosophy of MapReduce. The GATK provides a small but rich set of data access patterns that encompass the majority of analysis tool needs. Separating specific analysis calculations from common data management infrastructure enables us to optimize the GATK framework for correctness, stability, and CPU and memory efficiency and to enable distributed and shared memory parallelization. We highlight the capabilities of the GATK by describing the implementation and application of robust, scale-tolerant tools like coverage calculators and single nucleotide polymorphism (SNP) calling. We conclude that the GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.
The Nucleocapsid Protein of Coronaviruses Acts as a Viral Suppressor of RNA Silencing in Mammalian Cells (2015)

RNA interference (RNAi) is a process of eukaryotic posttranscriptional gene silencing that functions in antiviral immunity in plants, nematodes, and insects. However, recent studies provided strong supports that RNAi also plays a role in antiviral mechanism in mammalian cells. To combat RNAi-mediated antiviral responses, many viruses encode viral suppressors of RNA silencing (VSR) to facilitate their replication. VSRs have been widely studied for plant and insect viruses, but only a few have been defined for mammalian viruses currently. We identified a novel VSR from coronaviruses, a group of medically important mammalian viruses including Severe acute respiratory syndrome coronavirus (SARS-CoV), and showed that the nucleocapsid protein (N protein) of coronaviruses suppresses RNAi triggered by either short hairpin RNAs or small interfering RNAs in mammalian cells. Mouse hepatitis virus (MHV) is closely related to SARS-CoV in the family Coronaviridae and was used as a coronavirus replication model. The replication of MHV increased when the N proteins were expressed in trans, while knockdown of Dicer1 or Ago2 transcripts facilitated the MHV replication in mammalian cells. These results support the hypothesis that RNAi is a part of the antiviral immunity responses in mammalian cells. IMPORTANCE RNAi has been well known to play important antiviral roles from plants to invertebrates. However, recent studies provided strong supports that RNAi is also involved in antiviral response in mammalian cells. An important indication for RNAi-mediated antiviral activity in mammals is the fact that a number of mammalian viruses encode potent suppressors of RNA silencing. Our results demonstrate that coronavirus N protein could function as a VSR through its double-stranded RNA binding activity. Mutational analysis of N protein allowed us to find out the critical residues for the VSR activity. Using the MHV-A59 as the coronavirus replication model, we showed that ectopic expression of SARS-CoV N protein could promote MHV replication in RNAi-active cells but not in RNAi-depleted cells. These results indicate that coronaviruses encode a VSR that functions in the replication cycle and provide further evidence to support that RNAi-mediated antiviral response exists in mammalian cells.
The products of hydrolysis of cyclic orthoesters as a function of pH and the theory of stereoelectronic control (1985)

The acid hydrolysis of cyclic orthoesters 1, 3–6 (R = Me), and 2 (R = Me and Et) as a function of pH was studied. The bicyclic orthoester 5 yields mainly the hydroxy-ester (less than 5% lactone), and this result is essentially independent of pH. For the other orthoesters, the relative percentage of products differs for each case and varies with pH. At pH ≤ 3, the percentage of lactone is always larger than at pH &gt; 3. These results are explained on the basis of the stereoelectronic theory for the cleavage of tetrahedral intermediates.
哈萨克斯坦总统对《关于组织共和国对外经济活动的补充措施》修改和补充令 (1994)

为了进一步实现哈萨克斯坦共和国经济实体外贸活动自由化,我命令: (1)对1993年7月30日发布的1311号《关于组织共和国对外经济活动的补充措施》总统令(《共和国文件汇编》1993年第26期316页)做出下列修改和补充: 第2条按如下文字表述: “2.共和国经济实体从事国家级的产品出口,其中包括按确定的配额,既可通过共和国对外经济联络部
Differential Transcriptional Regulation of CD161 and a Novel Gene, 197/15a , by IL-2, IL-15, and IL-12 in NK and T Cells (1998)

Cytokine-mediated enhancement of spontaneous cytotoxicity depends, at least in part, on modulation of the expression of surface molecules responsible for recognition of target cell structures and triggering or inhibition of the cytotoxic machinery. We previously demonstrated that expression of transcription factors (e.g., Egr-1, JunB, and c-Fos) is differentially regulated by IL-2 and IL-12. Here we show that expression of CD161/NKR-P1A, a molecule involved in triggering cytotoxicity, is specifically upregulated by IL-12. CD161 transcription, mRNA accumulation, and surface expression are increased by IL-12. Other cytokines sharing the IL-2R beta- and/or common gamma-chains (i.e., IL-15, IL-4, and IL-7) do not mediate these effects. In an effort to analyze the mechanisms by which IL-2, IL-12, and IL-15 differentially regulate gene transcription, we have isolated a novel gene, 197/15a, the expression of which in NK and T cells is down-regulated by IL-2 and IL-15, up-regulated by IL-12, and not affected by IL-4 and IL-7. IL-2 and IL-15 act, at least in part, repressing 197/15a transcription; their effect on 197/15a mRNA accumulation is partially independent of novel protein synthesis, likely not mediated by JunB, Bcl-2, or Bax, and requires the activity of rapamycin-sensitive molecule(s). The observation that IL-2 and IL-12 differentially modulate CD161 expression suggests the existence of cytokine-specific mechanisms of modulation of spontaneous cytotoxicity based on the regulation of expression of surface molecules involved in target cell recognition and/or triggering of the cytolytic machinery.