gebhart/patrepeval huggingface dataset:
An apparent Bacillus subtilis folic acid biosynthetic operon containing pab, an amphibolic trpG gene, a third gene required for synthesis of para-aminobenzoic acid, and the dihydropteroate synthase gene (1990)

McDonald and Burke (J. Bacteriol. 149:391-394, 1982) previously cloned a sulfanilamide-resistance gene, sul, residing on a 4.9-kb segment of Bacillus subtilis chromosomal DNA, into plasmid pUB110. In this study we determined the nucleotide sequence of the entire 4.9-kb fragment. Genes identified on the fragment include pab, trpG, pabC, sul, one complete unidentified open reading frame, and one incomplete unidentified open reading frame. The first three of these genes, pab, trpG, and pabC, are required for synthesis of p-aminobenzoic acid. The trpG gene encodes an amphibolic glutamine amidotransferase required for synthesis of both p-aminobenzoate and anthranilate, the latter an intermediate in the tryptophan biosynthetic pathway. The pabC gene may encode a B. subtilis analog of enzyme X, an enzyme needed for p-aminobenzoate synthesis in Escherichia coli. The sul gene probably encodes dihydropteroate synthase, the enzyme responsible for formation of 7,8-dihydropteroate, the immediate precursor of folic acid. All six of the cloned genes are arranged in a single operon. Since all four of the identified genes are needed for folate biosynthesis, we refer to this operon as a folic acid operon. Expression of the trpG gene is known to be negatively controlled by tryptophan. We propose that this regulation is at the level of translation. This hypothesis is supported by the finding of an apparent Mtr-binding site which overlaps with the trpG ribosome-binding site.
Visually exploring multi-dimensional code couplings (2011)

Dependencies and coupling relationships between code entities can be manifold. They form a graph structure with several different types of edges. Visualizing these graphs presents two challenges: the often large size of the graphs and the readable representation of the different edge types. In this paper we present a new node-link graph visualization technique addressing these challenges. Different types of edges are represented in multiple, small diagrams. These diagrams are placed side-by-side like the pictures of a comic strip. Among other things, edge bundling is applied to improve the scalability of the visualization. Elaborate interaction techniques with respect to focusing and merging data aim at providing help for comparing different edge types. A case study demonstrates how the visualization can be used to analyze a mid-size software project in practice.
Novel pharmacological chaperones that correct phenylketonuria in mice (2012)

Phenylketonuria (PKU) is caused by inherited phenylalanine-hydroxylase (PAH) deficiency and, in many genotypes, it is associated with protein misfolding. The natural cofactor of PAH, tetrahydrobiopterin (BH(4)), can act as a pharmacological chaperone (PC) that rescues enzyme function. However, BH(4) shows limited efficacy in some PKU genotypes and its chemical synthesis is very costly. Taking an integrated drug discovery approach which has not been applied to this target before, we identified alternative PCs for the treatment of PKU. Shape-focused virtual screening of the National Cancer Institute's chemical library identified 84 candidate molecules with potential to bind to the active site of PAH. An in vitro evaluation of these yielded six compounds that restored the enzymatic activity of the unstable PAHV106A variant and increased its stability in cell-based assays against proteolytic degradation. During a 3-day treatment study, two compounds (benzylhydantoin and 6-amino-5-(benzylamino)-uracil) substantially improved the in vivo Phe oxidation and blood Phe concentrations of PKU mice (Pah(enu1)). Notably, benzylhydantoin was twice as effective as tetrahydrobiopterin. In conclusion, we identified two PCs with high in vivo efficacy that may be further developed into a more effective drug treatment of PKU.
The Platelet Glycoprotein Ib&hyphen;V&hyphen;IX System: Regulation of Gene Expression (1996)

Platelet glycoproteins (GPs) Ib-V-IX form the surface receptor for von Willebrand factor, and this receptor-ligand interaction mediates the shear-dependent adhesion of platelets to damaged arterial vessel walls. The receptor is a multicomponent structure consisting of four distinct polypeptides (heterodimeric GPIb: Ib alpha-Mr143k and Ib beta-Mr22k; GPV-Mr83k; GPIX-Mr20k), and each of the four cDNAs and genes has been cloned and characterized. The genes appear to have evolved from a common progenitor genomic sequence related to that encoding GPIX. They share simple structures with few introns and possess common consensus regulatory sequences (GATA, ets, Sp-1) in their 5' flanks. Both the GPIb alpha and the GPIX promoters have been analyzed by transfection of reporter constructs into hematopoietic and nonhematopoietic cells. The promoters function in a tissue-specific fashion, and gel shift and mutational analyses indicate that GATA and ets sequences regulate activity. In the case of the GPIX promoter, footprints confirm the role of the ets-related consensus region. Recent studies of GPIb beta transcriptional regulation suggest that an aberrant polyadenylation signal, located in the 3' end of the gene immediately upstream of the GPIb beta gene, allows in vitro expression of a rare extended fusion transcript encoding both the upstream protein and GPIb beta. Little detailed information is available in regard to expression of the GPV gene. In summary, the genes of the GPIb-V-IX system display features of other megakaryocyte/platelet genes, but the unique regulatory events that direct the selective expression of these genes in megakaryocytes remain to be defined.
Rho and Rac but not Cdc42 regulate endothelial cell permeability (2001)

Endothelial permeability induced by thrombin and histamine is accompanied by actin stress fibre assembly and intercellular gap formation. Here, we investigate the roles of the Rho family GTPases Rho1, Rac1 and Cdc42 in regulating endothelial barrier function, and correlate this with their effects on F-actin organization and intercellular junctions. RhoA, Rac1 and Cdc42 proteins were expressed efficiently in human umbilical vein endothelial cells by adenovirus-mediated gene transfer. We show that inhibition of Rho prevents both thrombin- and histamine-induced increases in endothelial permeability and decreases in transendothelial resistance. Dominant-negative RhoA and a Rho kinase inhibitor, Y-27632, not only inhibit stress fibre assembly and contractility but also prevent thrombin- and histamine-induced disassembly of adherens and tight junctions in endothelial cells, providing an explanation for their effects on permeability. In contrast, dominant-negative Rac1 induces permeability in unstimulated cells and enhances thrombin-induced permeability, yet inhibits stress fibre assembly, indicating that increased stress fibre formation is not essential for endothelial permeability. Dominant-negative Cdc42 reduces thrombin-induced stress fibre formation and contractility but does not affect endothelial cell permeability or responses to histamine. These results demonstrate that Rho and Rac act in different ways to alter endothelial barrier function, whereas Cdc42 does not affect barrier function.
TLRs in the Gut.IV. Negative regulation of Toll-like receptors and intestinal homeostasis: addition by subtraction (2007)

Toll-like receptors (TLRs) are a family of transmembrane proteins that recognize conserved molecular motifs on microorganisms. Ligand binding to TLRs initiates signaling cascades that activate NF-kappaB, MAPK, and interferon response factors. These culminate in cellular responses including activation of antimicrobial killing mechanisms, production of cytokines and chemokines, maturation of antigen presenting cells, and the recruitment of the adaptive immune response. Intestinal epithelial cells represent a unique population of cells that exist in direct contact with a biomass of bacteria. Initiation of TLR signaling is tightly regulated because prolonged and excessive activation of TLRs can lead to uncontrolled inflammation detrimental to the host. Varied mechanisms appear to contribute to control of TLR activation in the intestinal epithelium. These include the collective effects of several negative regulators that include IRAK-M, TOLLIP, SIGIRR, A20, Nod2, and PPARgamma. However, it remains to be determined whether they comprise the entire spectrum of negative control mechanisms and how they are bypassed to trigger activation during challenge by pathogens.
Cost Optimization of Thermoelectric Sub-Cooling in Air-cooled CO2 Air Conditioners (2016)

This paper presents a cost-effective enhancement of a trans-critical carbon dioxide (CO2) cycle in air-conditioning mode by utilizing a thermoelectric sub-cooler. It is well-documented that the cooling COP of the transcritical CO2 cycle decreases as the ambient air temperature significantly increases above the critical temperature of the refrigerant.Â A high gas cooler outlet temperature limits the enthalpy of evaporation so that the air-conditioning cooling performance is reduced. Sub-cooling is known as a mitigation method to this problem.Â However, adding a small-scale heat pump to a residential or light commercial air conditioner can be quite costly. Therefore, a thermoelectric solid-state sub-cooler is proposed. The thermoelectric cooling (TEC) devices utilized in small temperature differences ranging from 5 to 15 oC can be quite efficient since the intrinsic heat loss of the TEC by heat conduction in reverse direction of pumping heat is minimal. Based on the prior work, the optimum design for cost-per-performance shows that the cost for sub-cooling is dominated by the heat exchangers and it is not by the thermoelectric material itself. The TECs are compact and have a low thickness, which is in the range of a few mm. Hence the TEC modules can be integrated into the form factor of a plate heat exchanger. In this study, the cooling COP of the CO2 air conditioner is enhanced by approximately 12% using an optimally designed thermoelectric sub-cooler at an ambient temperature of 35 oC. This potential improvement is based on a figure-of-merit (ZT) of currently available thermoelectric materials (ZT~1). The seasonal primary energy efficiency and the cost performance of the optimized TE sub-cooled CO2 heat pump system will be presented in comparison to other compact sub-cooling technologies.
Phosphorothioate oligodeoxycytidine interferes with binding of HIV-1 gp120 to CD4. (1991)

In addition to their properties as sequence-specific inhibitors of gene expression, sequence nonspecific phosphorothioate oligodeoxynucleotides have been shown to protect against the cytopathic effects of HIV-1. Although these compounds are effective inhibitors of HIV-1 reverse transcriptase in vitro, it is not certain that they exert their cytoprotective effect only in this manner. Initial binding of the HIV-1 virion to cells involves the interaction of the viral envelope protein gp120 with CD4. In this report, we describe flow cytometric data and a solid-phase ELISA assay that document the ability of a phosphorothioate deoxycytidine 28-mer to interfere with this interaction by competing with gp120 binding to CD4. The biological importance of this interaction is demonstrated by the fact that phosphorothioate oligodeoxycytidine inhibits syncytium formation resulting from HIV-1-induced cell fusion. These data suggest that phosphorothioate oligodeoxynucleotides may exert their cytoprotective effects, perhaps at least in part, by interfering with the binding of HIV-1 to the target cells.
Histone deacetylase (HDAC) inhibitor activation of p21 WAF1 involves changes in promoter-associated proteins, including HDAC1 (2004)

Histone deacetylase (HDAC) inhibitors (HDACi) cause cancer cell growth arrest and/or apoptosis in vivo and in vitro. The HDACi suberoylanilide hydroxamic acid (SAHA) is in phase I/II clinical trials showing significant anticancer activity. Despite wide distribution of HDACs in chromatin, SAHA alters the expression of few genes in transformed cells. p21(WAF1) is one of the most commonly induced. SAHA does not alter the expression of p27(KIPI), an actively transcribed gene, or globin, a silent gene, in ARP-1 cells. Here we studied SAHA-induced changes in the p21(WAF1) promoter of ARP-1 cells to better understand the mechanism of HDACi gene activation. Within 1 h, SAHA caused modifications in acetylation and methylation of core histones and increased DNase I sensitivity and restriction enzyme accessibility in the p21(WAF1) promoter. These changes did not occur in the p27(KIPI) or epsilon-globin gene-related histones. The HDACi caused a marked decrease in HDAC1 and Myc and an increase in RNA polymerase II in proteins bound to the p21(WAF1) promoter. Thus, this study identifies effects of SAHA on p21(WAF1)-associated proteins that explain, at least in part, the selective effect of HDACi in altering gene expression.
Sarcopenia, Cachexia and Aging: Diagnosis, Mechanisms and Therapeutic Options - A Mini-Review (2014)

By the year 2050, individuals over the age of 65 years will comprise 20% of the US population. Loss of muscle mass and strength is common in this age group and it is associated with increased dependence, frailty and mortality. Sarcopenia, defined as the loss of muscle mass and function associated with aging, and cachexia, defined as weight loss due to an underlying illness, are muscle wasting disorders of particular relevance in the aging population, but they go largely unrecognized. In this review we highlight the common pathophysiological mechanisms underlying muscle loss in sarcopenia and cachexia, the factors unique to each condition and means of diagnosing and differentiating them clinically. Therapeutic options including exercise, nutritional therapy, androgens and growth hormone as well as their practical limitations are discussed. We also shed light on newer agents being developed as potential therapeutic options for wasting diseases.
Synthesis and application of derivatizable oligonucleotides (1987)

To investigate protein-DNA interactions, we have synthesized a versatile phthalimide-protected 5-(3-aminopropyl)-2'-deoxyuridine nucleoside probe. The modified residue was incorporated into deoxyoligonucleotides by automated synthesis. The standard oligonucleotide workup also exposed the pendent amino group, which was found to react with either fluorescent labelling agents or, as detailed below, a photoactivatable cross-linking agent. In the dark, a strand with a photolabile group adjacent to the 3' end served as a primer for synthetic template-directed DNA synthesis by the Klenow fragment of E. coli DNA polymerase I, by bacteriophage T4 DNA polymerase, and by avian myeloblastosis virus (AMV) reverse transcriptase. Brief illumination with 302 nm light afforded covalent complexes between DNA and the polymerases; labelling of AMV reverse transcriptase was predominantly in the beta subunit.
Chemical and Electrochemical Electron-Transfer Theory (1964)

One of the active areas in reaction kinetics during the post-war years has&#13;\nbeen that of electron-transfer reactions. These reactions constitute one type&#13;\nof oxidation-reduction process and include both chemical and electrochemical&#13;\nsystems. Many rate constants have now been measured (1-8) and&#13;\nthey have stimulated a variety of theoretical studies (9-37). The field has&#13;\nbeen characterized by a strong interplay of theory and experiment, which&#13;\nnow includes the testing of theoretically predicted quantitative correlations&#13;\n(34). Because of a certain unique feature of the purely electron-transfer&#13;\nreactions--the absence of bond rupture in the reaction step--these correlations&#13;\nare unusual. They do not have the arbitrary parameters that occur&#13;\nin theoretical studies of most other reactions in chemical kinetics. This review&#13;\nwill be limited to purely electron transfer reactions.
Waveguided Ge/Si Avalanche Photodiode With Separate Vertical SEG-Ge Absorption, Lateral Si Charge, and Multiplication Configuration (2009)

A novel Si-waveguide-integrated Ge/Si avalanche photodiode (APD) is demonstrated for the first time, in which light propagating along the Si waveguide is evanescently absorbed by an overlaying Ge layer selectively grown on it, whereas the avalanche multiplication of photoexcited carriers occurs laterally in the Si-waveguide layer. The APD provides a responsivity of ~7.2 A/W at 1550 nm, which is ~26 times larger than the corresponding vertical Ge/Si p-i-n photodiode, and exhibits a 3-dB bandwidth of ~3.3 GHz, a dark current of ~22 ¿A at 22-V bias, and an excess noise factor of ~4, respectively.
Proxy Prefix Caching for Multimedia Streams TITLE2 (1998)

Proxies are emerging as an important way to reduce user-perceived latency and network resource requirements in the Internet. While relaying traffic between servers and clients, a proxy can cache resources in the hope of satisfying future client requests directly at the proxy. However, existing techniques for caching text and images are not appropriate for the rapidly growing number of continuous media streams. In addition, high latency and loss rates in the Internet make it difficult to stream audio and video without introducing a large playback delay. To address these problems, we propose that, instead of caching entire audio or video streams (which may be quite large), the proxy should store a {\em prefix\/} consisting of the initial frames of each clip. Upon receiving a request for the stream, the proxy immediately initiates transmission to the client, while simultaneously requesting the remaining frames from the server. In addition to hiding the latency between the server and the proxy, storing the prefix of the stream aids the proxy in performing {\em workahead smoothing\/} into the client playback buffer. By transmitting large frames in advance of each burst, workahead smoothing substantially reduces the peak and variability of the network resource requirements along the path from the proxy to the client. We describe how to construct a smooth transmission schedule, based on the size of the prefix, smoothing, and playback buffers, without increasing client playback delay. Through experiments with MPEG-1 and MPEG-2 traces, we show how a few megabytes of buffer space at the proxy can offer substantial reductions in the bandwidth requirements of variable-bit-rate video. Drawing on these results, we present guidelines for allocating buffer space for each stream, and how to effectively share buffer and bandwidth resources among multiple clients and streams.
Endothelial potential of human embryonic stem cells (2007)

Growing interest in using endothelial cells for therapeutic purposes has led to exploring human embryonic stem cells as a potential source for endothelial progenitor cells. Embryonic stem cells are advantageous when compared with other endothelial cell origins, due to their high proliferation capability, pluripotency, and low immunogenity. However, there are many challenges and obstacles to overcome before the vision of using embryonic endothelial progenitor cells in the clinic can be realized. Among these obstacles is the development of a productive method of isolating endothelial cells from human embryonic stem cells and elucidating their differentiation pathway. This review will focus on the endothelial potential of human embryonic stem cells that is described in current studies, with respect to the differentiation of human embryonic stem cells to endothelial cells, their isolation, and their characterization.
99mTc Labeling of Highly Potent Small Peptides (1997)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXT99mTc Labeling of Highly Potent Small PeptidesShuang Liu, D. Scott Edwards, and John A. BarrettView Author Information Radiopharmaceuticals Division, The DuPont Merck Pharmaceutical Company, 331 Treble Cove Road, North Billerica, Massachusetts 01862Cite this: Bioconjugate Chem. 1997, 8, 5, 621–636Publication Date (Web):September 25, 1997Publication History Received21 April 1997Published online25 September 1997Published inissue 1 September 1997https://pubs.acs.org/doi/10.1021/bc970058bhttps://doi.org/10.1021/bc970058breview-articleACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views1001Altmetric-Citations108LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Labeling,Ligands,Nuclear medicine,Peptides and proteins,Technetium Get e-Alerts
Preparation of a biomimetic nanocomposite scaffold for bone tissue engineering via mineralization of gelatin hydrogel and study of mineral transformation in simulated body fluid (2012)

In this study, double diffusion method in a physiologically relevant environment was used to prepare a biomimetic gelatin-amorphous calcium phosphate nanocomposite scaffold. The precipitated calcium phosphate within gelatin as well as produced nanocomposite scaffolds were characterized by the commonly used bulk techniques. The results showed that nanocomposite scaffolds were porous with three-dimensionally interconnected microstructure, pore size ranging from 150 to 350 μm. Porosity was about 82% and nanocrystalline precipitated minerals were dispersed evenly among gelatin fibers. A mineral containing amorphous calcium phosphate and brushite precipitate was formed within the gelatin matrix at 4°C. After incubation in SBF solution at 37°C for 5 days, the mineral phase was transformed to nanocrystalline hydroxyapatite. It should be noted that precursor phases inside a scaffold implanted into the body can result in biomimetic conversion of precursors to hydroxyapatite that is very similar to the bone mineral and has a profound level of biocompatibility. Thus, our results highlight the potential use of engineered biomimetic bone tissue scaffolds in the bone tissue repair process.
Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial (2014)

Genentech.