gebhart/patrepeval huggingface dataset:
The R1 Conjugative Plasmid Increases Escherichia coli Biofilm Formation through an Envelope Stress Response (2008)

Differential gene expression in biofilm cells suggests that adding the derepressed conjugative plasmid R1drd19 increases biofilm formation by affecting genes related to envelope stress (rseA and cpxAR), biofilm formation (bssR and cstA), energy production (glpDFK), acid resistance (gadABCEX and hdeABD), and cell motility (csgBEFG, yehCD, yadC, and yfcV); genes encoding outer membrane proteins (ompACF), phage shock proteins (pspABCDE), and cold shock proteins (cspACDEG); and phage-related genes. To investigate the link between the identified genes and biofilm formation upon the addition of R1drd19, 40 isogenic mutants were classified according to their different biofilm formation phenotypes. Cells with class I mutations (those in rseA, bssR, cpxA, and ompA) exhibited no difference from the wild-type strain in biofilm formation and no increase in biofilm formation upon the addition of R1drd19. Cells with class II mutations (those in gatC, yagI, ompC, cspA, pspD, pspB, ymgB, gadC, pspC, ymgA, slp, cpxP, cpxR, cstA, rseC, ompF, and yqjD) displayed increased biofilm formation compared to the wild-type strain but decreased biofilm formation upon the addition of R1drd19. Class III mutants showed increased biofilm formation compared to the wild-type strain and increased biofilm formation upon the addition of R1drd19. Cells with class IV mutations displayed increased biofilm formation compared to the wild-type strain but little difference upon the addition of R1drd19, and class V mutants exhibited no difference from the wild-type strain but increased biofilm formation upon the addition of R1drd19. Therefore, proteins encoded by the genes corresponding to the class I mutant phenotype are involved in R1drd19-promoted biofilm formation, primarily through their impact on cell motility. We hypothesize that the pili formed upon the addition of the conjugative plasmid disrupt the membrane (induce ompA) and activate the two-component system CpxAR as well as the other envelope stress response system, RseA-sigma(E), both of which, along with BssR, play a key role in bacterial biofilm formation.
Electrostriction mechanism of soliton interaction in optical fibers (1990)

In contrast to the mechanism of interaction determined by the Kerr nolinearity, the electrostrictive interaction between picosecond pulses in optical fibers can occur when the temporal interval between them is much greater than their duration. The width of the interval is determined by the lifetime of the sound wave in the fiber core region, i.e., ~1 nsec. It follows from our calculations that for long propagation distances (L &gt; 1000 km) the relative temporal separation of the interacting pulses can reach hundreds of picoseconds at the temporal interval between them of ~1 nsec.
Data from Network Analysis Identifies an HSP90-Central Hub Susceptible in Ovarian Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Epithelial ovarian cancer (EOC) is usually detected at an advanced stage and is frequently lethal. Although many patients respond to initial surgery and standard chemotherapy consisting of a platinum-based agent and a taxane, most experience recurrence and eventually treatment-resistant disease. Although there have been numerous efforts to apply protein-targeted agents in EOC, these studies have so far documented little efficacy. Our goal was to identify broadly susceptible signaling proteins or pathways in EOC.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; As a new approach, we conducted data-mining meta-analyses integrating results from multiple siRNA screens to identify gene targets that showed significant inhibition of cell growth. On the basis of this meta-analysis, we established that many genes with such activity were clients of the protein chaperone HSP90. We therefore assessed ganetespib, a clinically promising second-generation small-molecule HSP90 inhibitor, for activity against EOC, both as a single agent and in combination with cytotoxic and targeted therapeutic agents.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Ganetespib significantly reduced cell growth, induced cell-cycle arrest and apoptosis &lt;i&gt;in vitro&lt;/i&gt;, inhibited growth of orthotopic xenografts and spontaneous ovarian tumors in transgenic mice &lt;i&gt;in vivo&lt;/i&gt;, and inhibited expression and activation of numerous proteins linked to EOC progression. Importantly, paclitaxel significantly potentiated ganetespib activity in cultured cells and tumors. Moreover, combined treatment of cells with ganetespib and siRNAs or small molecules inhibiting genes identified in the meta-analysis in several cases resulted in enhanced activity.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; These results strongly support investigation of ganetespib, a single-targeted agent with effects on numerous proteins and pathways, in augmenting standard EOC therapies. &lt;i&gt;Clin Cancer Res; 19(18); 5053–67. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Incorporation of 65Zn in Rat Liver Nuclei (1970)

The intracellular distribution of 65Zn in rat liver has been studied in vivo and in vitro 1 The highest 65Zn uptake can be observed in the nuclear fraction. A maximum occurs after approx. 5 hours which is in contrast to the rapid rise of detectable 65Zn in the whole homogenate appearing immediately after the intraperitoneal injections of this metal ion. Further, 65Zn is retained by the nuclei for a much longer period. When Zn-deficient rats are employed 65Zn uptake is considerable enhanced at the beginning. However, the total 65Zn radioactivity of whole liver homogenate is only slightly increased. 2 The uptake of 65Zn by isolated liver nuclei suggests a strong temperature dependence in vitro. No 65Zn uptake at all can be measured when nuclei are employed which have been stored at –25° for two months. 3 An attempt has been made to isolate a double stranded DNA-65Zn complex from liver nuclei derived from 65Zn injected rats or from nuclei incubated with 65Zn. However, high ionic strength buffers or phenol displace 65Zn from the polynucleotide during the isolation procedure. 4 The intracellular 65Zn distribution in the liver portions remaining after partial hepatectomy in rats is in accordance with the results obtained above.
Relation between the Chemical Properties of Aromatic Carboxylic Acids and the Tc-Complexes Obtained Using Sn(II) as Reductant. Α Potentiometrie-Photometrie Study (1988)

Article Relation between the Chemical Properties of Aromatic Carboxylic Acids and the Tc-Complexes Obtained Using Sn(II) as Reductant. Α Potentiometrie-Photometrie Study was published on March 1, 1988 in the journal Radiochimica Acta (volume 43, issue 3).
A Fourier theory for cast shadows (2005)

Cast shadows can be significant in many computer vision applications, such as lighting-insensitive recognition and surface reconstruction. Nevertheless, most algorithms neglect them, primarily because they involve nonlocal interactions in nonconvex regions, making formal analysis difficult. However, many real instances map closely to canonical configurations like a wall, a V-groove type structure, or a pitted surface. In particular, we experiment with 3D textures like moss, gravel, and a kitchen sponge, whose surfaces include canonical configurations like V-grooves. This paper takes a first step toward a formal analysis of cast shadows, showing theoretically that many configurations can be mathematically analyzed using convolutions and Fourier basis functions. Our analysis exposes the mathematical convolution structure of cast shadows and shows strong connections to recent signal-processing frameworks for reflection and illumination.
Deleting exon 55 from the nebulin gene induces severe muscle weakness in a mouse model for nemaline myopathy (2013)

Nebulin--a giant sarcomeric protein--plays a pivotal role in skeletal muscle contractility by specifying thin filament length and function. Although mutations in the gene encoding nebulin (NEB) are a frequent cause of nemaline myopathy, the most common non-dystrophic congenital myopathy, the mechanisms by which mutations in NEB cause muscle weakness remain largely unknown. To better understand these mechanisms, we have generated a mouse model in which Neb exon 55 is deleted (Neb(ΔExon55)) to replicate a founder mutation seen frequently in patients with nemaline myopathy with Ashkenazi Jewish heritage. Neb(ΔExon55) mice are born close to Mendelian ratios, but show growth retardation after birth. Electron microscopy studies show nemaline bodies--a hallmark feature of nemaline myopathy--in muscle fibres from Neb(ΔExon55) mice. Western blotting studies with nebulin-specific antibodies reveal reduced nebulin levels in muscle from Neb(ΔExon55) mice, and immunofluorescence confocal microscopy studies with tropomodulin antibodies and phalloidin reveal that thin filament length is significantly reduced. In line with reduced thin filament length, the maximal force generating capacity of permeabilized muscle fibres and single myofibrils is reduced in Neb(ΔExon55) mice with a more pronounced reduction at longer sarcomere lengths. Finally, in Neb(ΔExon55) mice the regulation of contraction is impaired, as evidenced by marked changes in crossbridge cycling kinetics and by a reduction of the calcium sensitivity of force generation. A novel drug that facilitates calcium binding to the thin filament significantly augmented the calcium sensitivity of submaximal force to levels that exceed those observed in untreated control muscle. In conclusion, we have characterized the first nebulin-based nemaline myopathy model, which recapitulates important features of the phenotype observed in patients harbouring this particular mutation, and which has severe muscle weakness caused by thin filament dysfunction.
Specializing FGPU for Persistent Deep Learning (2019)

Overlay architectures are a good way to enable fast development and debug on FPGAs at the expense of potentially limited performance when compared to fully customized FPGA designs. When used in concert with a hand-tuned FPGA solution, a performant overlay architecture can improve the time-to-solution and thus overall productivity of FPGA solutions. In this work, we tune and specialize FGPU, an open source OpenCL-programmable GPU overlay for FPGAs. We demonstrate that our PDL-FGPU architecture is able to maintain the ease-of-programming and generality of a software programmable soft GPU while achieving high performance due to specialization in the persistent deep learning domain. We also propose a easy method to specialize for different domains. PDL-FGPU includes new instructions, along with micro-architecture and compiler enhancements. We evaluate both the FGPU baseline and the proposed PDL-FGPU on a modern high-end Intel Stratix 10 2800 FPGA running a set of persistent DL applications (RNN, GRU, LSTM), as well as general non-DL applications to demonstrate generality. PDL-FGPU requires 1.5-3x more ALMs, 4.4-6.4x more M20ks, and 4.6-10x more DSPs than the FGPU baseline, but improves performance by 55-727x for persistent DL applications with an average 15% degradation on general non-PDL applications. We also demonstrate that the PDL-FGPU is only 4-7x slower than the Nvidia Volta V100 GPU.
Tissue-specific Antibodies Against the Fibroblast Insulin Receptor in a Patient with Lupus Nephritis and Hypoglycemia (1985)

We recently reported that the serum from a patient with lupus nephritis, insulin resistance, and hypoglycemia contains multiple populations of antibodies directed at the human insulin receptor. In the present study, we found a subpopulation of antibodies (eluted from a protein A-Sepharose affinity column at pH 4.3) directed at the human fibroblast insulin receptor. When tested against human placental membranes, IM-9 lymphocytes, circulating monocytes and erythrocytes, and isolated adipocytes, the antibody subpopulation did not compete with 125I-insulin for binding to its receptor. In contrast, the antibody subpopulation competed with 125I-insulin for binding to the human fibroblast insulin receptor. This antibody subpopulation stimulated [3H]alpha-aminoisobutyric acid [( 3H]AIB) uptake to these cells. Unlike the effect of insulin, however, this regulation of transport was not antagonized by a mouse monoclonal antibody to the human insulin receptor that inhibits 125I-insulin binding. These studies indicate, therefore, that a tissue-specific antibody subpopulation can occur spontaneously in patients with antibodies to the human insulin receptor. Furthermore, they indicate the presence of anti-insulin receptor autoantibodies specifically directed against a tissue that is not primarily involved in glucose metabolism.
Synthesis of an extra-large molecular sieve using proton sponges as organic structure-directing agents (2013)

The synthesis of crystalline microporous materials containing large pores is in high demand by industry, especially for the use of these materials as catalysts in chemical processes involving bulky molecules. An extra-large-pore silicoaluminophosphate with 16-ring openings, ITQ-51, has been synthesized by the use of bulky aromatic proton sponges as organic structure-directing agents. Proton sponges show exceptional properties for directing extra-large zeolites because of their unusually high basicity combined with their large size and rigidity. This extra-large-pore material is stable after calcination, being one of the very few examples of hydrothermally stable molecular sieves containing extra-large pores. The structure of ITQ-51 was solved from submicrometer-sized crystals using the rotation electron diffraction method. Finally, several hypothetical zeolites related to ITQ-51 have been proposed.
Methods for Monitoring Canine Prostate Size: Internal and External Caliper Measurements (1985)

No AccessJournal of Urology1 Sep 1985Methods for Monitoring Canine Prostate Size: Internal and External Caliper Measurements S.J. Berry, R. Sterner, D.S. Coffey, and L.L. Ewing S.J. BerryS.J. Berry More articles by this author , R. SternerR. Sterner More articles by this author , D.S. CoffeyD.S. Coffey More articles by this author , and L.L. EwingL.L. Ewing More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)47343-5AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Methods for Monitoring Canine Prostate Size: Internal and External Caliper Measurements." The Journal of Urology, 134(3), p. 636 © 1985 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 134Issue 3September 1985Page: 636 Advertisement Copyright & Permissions© 1985 by The American Urological Association Education and Research, Inc.Metrics Author Information S.J. Berry More articles by this author R. Sterner More articles by this author D.S. Coffey More articles by this author L.L. Ewing More articles by this author Expand All Advertisement PDF downloadLoading ...
Using Unentangled Oligomers To Toughen Materials (2018)

Entanglements between polymer chains are responsible for the strength and toughness of polymeric materials. When the chains are too short to form entanglements, the polymer becomes weak and brittle. Here we show that molecular bridging of oligomers in molecular-scale confinement can dramatically toughen materials even when intermolecular entanglements are completely absent. We describe the fabrication of nanocomposite materials that confine oligomer chains to molecular-scale dimensions and demonstrate that partially confined unentangled oligomers can toughen materials far beyond rule-of-mixtures estimates. We also characterize how partially confined oligomers affect the kinetics of nanocomposite cracking in moist environments and show that the presence of a backfilled oligomeric phase within a nanoporous organosilicate matrix leads to atomistic crack path meandering in which the failure path is preferentially located within the matrix phase.
Nonacog gamma, a novel recombinant factor IX with low factor IXa content for treatment and prophylaxis of bleeding episodes (2015)

Nonacog gamma is a new recombinant factor IX to treat factor IX deficiency. It is indicated for control of bleeding episodes, perioperative management and routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia B. Nonacog gamma was first approved in the USA in June 2013 under the trade name RIXUBIS followed by market approvals in Australia and the EU in 2014, and marketing authorization decision is pending in Japan. Nonacog gamma is derived from a recombinant Chinese hamster ovary cell line using a state of the art biotechnological manufacturing process. Recombinant factor IX is produced by Baxter's protein-free fermentation technology, which was first developed for ADVATE. The product is purified and formulated in the absence of any human or animal-derived protein. Nonacog gamma was characterized both in comprehensive in vitro and in vivo non-clinical studies as well as in an extensive clinical trial program.
Discovery of Novel, Induced-Pocket Binding Oxazolidinones as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors (2013)

Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates β-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of β-catenin-mediated transcription and inhibit tumorigenesis. Compound 1 is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties. Herein, we describe the utilization of structure-based design and molecular modeling toward novel, potent, and selective tankyrase inhibitors with improved pharmacokinetic properties (39, 40).
Dibasic Benzo[b]thiophene Derivatives as a Novel Class of Active Site-Directed Thrombin Inhibitors. 1. Determination of the Serine Protease Selectivity, Structure−Activity Relationships, and Binding Orientation (1997)

ADVERTISEMENT RETURN TO ISSUELetterNEXTDibasic Benzo[b]thiophene Derivatives as a Novel Class of Active Site-Directed Thrombin Inhibitors. 1. Determination of the Serine Protease Selectivity, Structure−Activity Relationships, and Binding OrientationDaniel J. Sall, Jolie A. Bastian, Stephen L. Briggs, John A. Buben, Nickolay Y. Chirgadze, David K. Clawson, Michael L. Denney, Deborah D. Giera, Donetta S. Gifford-Moore, Richard W. Harper, Kenneth L. Hauser, Valentine J. Klimkowski, Todd J. Kohn, Ho-Shen Lin, Jefferson R. McCowan, Alan D. Palkowitz, Gerald F. Smith, Kumiko Takeuchi, Kenneth J. Thrasher, Jennifer M. Tinsley, Barbara G. Utterback, Sau-Chi B. Yan, and Minsheng ZhangView Author Information Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285 Cite this: J. Med. Chem. 1997, 40, 22, 3489–3493Publication Date (Web):October 24, 1997Publication History Received9 July 1997Published online24 October 1997Published inissue 1 October 1997https://pubs.acs.org/doi/10.1021/jm9704107https://doi.org/10.1021/jm9704107rapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views439Altmetric-Citations50LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Inhibition,Inhibitors,Peptides and proteins,Reaction products,Thiophenes Get e-Alerts
Overexpression of arginase in the aged mouse penis impairs erectile function and decreases eNOS activity: influence of in vivo gene therapy of anti-arginase (2006)

Since both increased nitric oxide (NO) synthase (NOS) abundance and diminished NO signaling have been reported in the aging penis, the role of NO in the adaptations of aging remains controversial. Here we tested the hypothesis that arginase, an enzyme that competes with NOS for the substrate l-arginine, contributes to erectile dysfunction with advanced age in the B6/129 mouse strain. Arginase protein abundance, mRNA expression, and enzyme activity were elevated in aged compared with young penile endothelial cells. In addition, endothelial NOS (NOS3) protein abundance was greater in aged versus young penile endothelial cells, whereas NOS activity and cGMP levels were reduced. Calcium-dependent l-arginine-to-l-citrulline conversion and cGMP formation increased significantly in aged mouse penes in the presence of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH). However, there was no effect on l-arginine-to-l-citrulline conversion or cGMP accumulation in the endothelium from young mouse penes. To assess the functional role of arginase in the inhibition of NOS pathway responsiveness in the penis, we evaluated the effects of ABH and an adeno-associated virus encoding an antisense sequence to arginase I (AAVanti-arginase) on erectile function in vivo. ABH and AAVanti-arginase enhanced endothelium-dependent erectile responses in the aged mice without altering endothelium-independent responses. Paralleling our in vitro observations, ABH or AAVanti-arginase did not affect vascular responses in the young mice. Inhibition of the arginase pathway improves endothelial function in the aging penile circulation, suggesting that the arginase pathway may be exploited to improve erectile dysfunction associated with aging.
Mitogen-activated protein kinase pathway: A critical regulator in tumor-associated macrophage polarization (2019)

The notion that inflammation is a critical component of cancer has been researched extensively. Tumor-associated macrophages (TAMs) are among the inflammatory cells that greatly influence cancer. In the tumor microenvironment (TME), macrophages can either stimulate or inhibit tumorigenesis. TAMs that stimulate tumor cell proliferation (M2-phenotype) enrich the TME with growth factors and immunosuppressive molecules, whereas tumor inhibitory TAMs (M1-phenotype) initiate the immune response to dampen tumor progression. Shifting between phenotypes is controlled by several components of the TME. Targeting macrophages, specifically inhibiting M2 TAMs, has been introduced successfully in cancer immunotherapy. However, signaling mechanisms underlining TAM polarization are largely unknown. This review analyzed studies of the role of mitogen-activated protein kinase (MAPK) as a determinant of macrophage polarization. It is proposed that activation of MAPK, particularly extracellular signal-regulated kinase 1/2 and p38, might favor the differentiation into M2 TAMs. Thus, pharmacological modification of MAPK pathways will potentially offer exciting new targets in cancer immunotherapy.