gebhart/patrepeval huggingface dataset:
Short Linear Motifs: Ubiquitous and Functionally Diverse Protein Interaction Modules Directing Cell Regulation (2014)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTShort Linear Motifs: Ubiquitous and Functionally Diverse Protein Interaction Modules Directing Cell RegulationKim Van Roey†, Bora Uyar†, Robert J. Weatheritt‡, Holger Dinkel†, Markus Seiler†, Aidan Budd†, Toby J. Gibson†, and Norman E. Davey*†§View Author Information† Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany‡ MRC Laboratory of Molecular Biology (LMB), Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom§ Department of Physiology, University of California, San Francisco, San Francisco, California 94143, United States*E-mail: [email protected]Cite this: Chem. Rev. 2014, 114, 13, 6733–6778Publication Date (Web):June 13, 2014Publication History Received17 October 2013Published online13 June 2014Published inissue 9 July 2014https://pubs.acs.org/doi/10.1021/cr400585qhttps://doi.org/10.1021/cr400585qreview-articleACS PublicationsCopyright © 2014 American Chemical SocietyRequest reuse permissionsArticle Views7806Altmetric-Citations326LEARN 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:Cell and molecular biology,Modification,Peptides and proteins,Post-translational modification,Receptors Get e-Alerts
SAT: a Late NS Protein of Porcine Parvovirus (2005)

The genomes of all members of the Parvovirus genus were found to contain a small open reading frame (ORF), designated SAT, with a start codon four or seven nucleotides downstream of the VP2 initiation codon. Green fluorescent protein or FLAG fusion constructs of SAT demonstrated that these ORFs were expressed. Although the SAT proteins of the different parvoviruses are not particularly conserved, they were all predicted to contain a membrane-spanning helix, and mutations in this hydrophobic stretch affected the localization of the SAT protein. SAT colocalized with calreticulin in the membranes of the endoplasmic reticulum and the nucleus. A knockout mutant (SAT(-)), with an unmodified VP sequence, showed a "slow-spreading" phenotype. These knockout mutants could be complemented with VP2(-) SAT(+) mutant. The SAT protein is a late nonstructural (NS) protein, in contrast to previously identified NS proteins, since it is expressed from the same mRNA as VP2.
Poisson Statistics of Combinatorial Library Sampling Predict False Discovery Rates of Screening (2017)

Microfluidic droplet-based screening of DNA-encoded one-bead-one-compound combinatorial libraries is a miniaturized, potentially widely distributable approach to small molecule discovery. In these screens, a microfluidic circuit distributes library beads into droplets of activity assay reagent, photochemically cleaves the compound from the bead, then incubates and sorts the droplets based on assay result for subsequent DNA sequencing-based hit compound structure elucidation. Pilot experimental studies revealed that Poisson statistics describe nearly all aspects of such screens, prompting the development of simulations to understand system behavior. Monte Carlo screening simulation data showed that increasing mean library sampling (ε), mean droplet occupancy, or library hit rate all increase the false discovery rate (FDR). Compounds identified as hits on k > 1 beads (the replicate k class) were much more likely to be authentic hits than singletons (k = 1), in agreement with previous findings. Here, we explain this observation by deriving an equation for authenticity, which reduces to the product of a library sampling bias term (exponential in k) and a sampling saturation term (exponential in ε) setting a threshold that the k-dependent bias must overcome. The equation thus quantitatively describes why each hit structure's FDR is based on its k class, and further predicts the feasibility of intentionally populating droplets with multiple library beads, assaying the micromixtures for function, and identifying the active members by statistical deconvolution.
Food‐Based Edible and Nutritive Electronics (2017)

Abstract A new class of electronic materials derived predominantly from natural foods and foodstuffs, with minimal levels of inorganic materials, is developed and studied to build edible electronic components and devices compatible with the gastrointestinal (GI) tract. A “toolkit” of food‐based electronic materials, fabrication schemes, basic device components, and functional devices with integrated sensing and wireless signal transmission is reported. These new materials establish the possibility to extend GI electronic devices beyond the ingested nondegradable systems to edible and nutritive systems, in which the described materials may be ingested and assimilated as metabolized nutrients. This study represents a new era of edible electronics with the potential to revolutionize modern biomedical technologies and devices.
From System F to Typed Assembly Language (Extended Version) (1997)

We motivate the design of a statically typed assembly language (TAL) and present a typepreserving translation from System F to TAL. The TAL we present is based on a conventional RISC assembly language, but its static type system provides support for enforcing high-level language abstractions, such as closures, tuples, and objects, as well as user-defined abstract data types. The type system ensures that well-typed programs cannot violate these abstractions. In addition, the typing constructs place almost no restrictions on low-level optimizations such as register allocation, instruction selection, or instruction scheduling. Our translation to TAL is specified as a sequence of type-preserving transformations, including CPS and closure conversion phases; type-correct source programs are mapped to type-correct assembly language. A key contribution is an approach to polymorphic closure conversion that is considerably simpler than previous work. The compiler and typed assembly language provide a fully automatic way to produce proof carrying code, suitable for use in systems where untrusted and potentially malicious code must be checked for safety before execution. 1
Inhibition of the multiple antibiotic resistance (mar) operon in Escherichia coli by antisense DNA analogs (1997)

The multiple antibiotic resistance operon (marORAB) in Escherichia coli controls intrinsic susceptibility and resistance to multiple, structurally different antibiotics and other noxious agents. A plasmid construct with marA cloned in the antisense direction reduced LacZ expression from a constitutively expressed marA::lacZ translational fusion and inhibited the induced expression of LacZ in cells bearing the wild-type repressed fusion. The marA antisense construction also decreased the multiple antibiotic resistance of a Mar mutant. Two antisense phosphorothioate oligonucleotides, one targeted to marO and the other targeted to marA of the mar operon, introduced by heat shock or electroporation reduced LacZ expression in the strain having the marA::lacZ fusion. One antisense oligonucleotide, tested against a Mar mutant of E. coli ML308-225, increased the bactericidal activity of norfloxacin. These studies demonstrate the efficacy of exogenously delivered antisense oligonucleotides targeted to the marRAB operon in inhibiting expression of this chromosomal regulatory locus.
Fault detection in continuous processes using multivariate statistical methods (2000)

The approach to process monitoring known as multivariate statistical process control (MSPC) has developed as a distinct technology, closely related to the field of fault detection and isolation. A body of technical research and industrial applications indicate a unique applicability to complex large-scale processes, but has paid relatively little attention to generic live process issues. In this paper, the impact of various classes of generic abnormality in the operation of continuous process plants on MSPC monitoring is investigated. It is shown how the effectiveness of the MSPC approach may be understood in terms of model and signal-based fault detection methods, and how the multivariate tools may be configured to maximize their effectiveness. A brief review of MSPC for the process industries is also presented, indicating the current state of the art.
Cell surface expression of functional hepatitis C virus E1 and E2 glycoproteins (2003)

Hepatitis C virus (HCV) glycoproteins E1 and E2 are believed to be retained in the endoplasmic reticulum (ER) or cis-Golgi compartment via retention signals located in their transmembrane domains. Here we describe the detection of E1 and E2 at the surface of transiently transfected HEK 293T and Huh7 cells. Surface-localized E1E2 heterodimers presented exclusively as non-covalently associated complexes. Surface-expressed E2 contained trans-Golgi modified complex/hybrid type carbohydrate and migrated diffusely between 70 and 90 kDa while intracellular E1 and E2 existed as high mannose 35 kDa and 70 kDa precursors, respectively. In addition, surface-localized E1E2 heterodimers were incorporated into E1E2-pseudotyped HIV-1 particles that were competent for entry into Huh7 cells. These studies suggest that functional HCV glycoproteins are not retained exclusively in the ER and transit through the secretory pathway.
Prevalence of obesity in the United States, 2009-2010. (2012)

The most recent national data on obesity prevalence among U.S. adults, adolescents, and children show that more than one-third of adults and almost 17% of children and adolescents were obese in 2009–2010. Differences in prevalence between men and women diminished between 1999–2000 and 2009–2010, with the prevalence of obesity among men reaching the same level as that among women. Age differences in obesity prevalence varied between men and women. The prevalence of obesity was higher among older women compared with younger women, but there was no difference by age in obesity prevalence among men. Among children and adolescents, the prevalence of obesity was higher among adolescents than among preschool-aged children. There has been no change in obesity prevalence in recent years; however, over the last decade there has been a significant increase in obesity prevalence among men and boys but not among women and girls overall. The Healthy People 2010 goals of 15% obesity among adults and 5% obesity among children were not met (6).
Normobaric Hypoxia and Nitroglycerin as Trigger Factors for Migraine (2006)

Migraine prevalence is increased in high-altitude populations and symptoms of acute mountain sickness mimic migraine symptoms. Here we tested whether normobaric hypoxia may trigger migraine attacks. As positive control we used nitrolgycerin (NTG), which has been shown to induce migraine attacks in up to 80% of migraineurs. Sixteen patients (12 females, mean age 28.9 +/- 7.2 years) suffering from migraine with (n = 8) and without aura (n = 8) underwent three different provocations (normobaric hypoxia, NTG and placebo) in a randomized, cross-over, double dummy design. Each provocation was performed on a separate day. The primary outcome measure was the proportion of patients developing a migraine attack according to the criteria of the International Headache Society within 8 h after provocation onset. Fourteen patients completed all three provocations. Migraine was provoked in six (42%) patients by hypoxia, in three (21%) by NTG and in two (14%) by placebo. The differences among groups were not significant (P = 0.197). The median time to attacks was 5 h. In conclusion, the (remarkably) low response rate to NTG is surprising in view of previous data. Further studies are required to establish fully the potency of hypoxia in triggering migraine attacks.
Interferon induction of fibroblast proteins with guanylate binding activity. (1983)

Treatment of human diploid fibroblastic cells with interferon induces the synthesis of two guanylate binding proteins (GBP) with molecular weights of 67,000 and 56,000. The Mr = 67,000 protein (67K GBP) is synthesized upon treatment with either alpha-, beta-, or gamma-interferon. Among these interferons, gamma-interferon induces a higher level of 67K GBP synthesis. The 67K GBP synthesized in either beta- or gamma-interferon-treated cells has two charge forms with isoelectric points of 6.0 and 5.8, respectively. The synthesis of the Mr = 56,000 protein is induced by the treatment using either alpha- or beta-interferon, but its synthesis in gamma-interferon-treated cells is undetectable. The amounts of the radioactive GBPs synthesized in human fibroblasts are proportional to the amounts of the purified beta-interferon used for the inductions. Syntheses of GBPs require the transcription of cellular genes because their syntheses are completely blocked by actinomycin D treatments. The mRNA for the 67K GBP is found in fibroblasts that are treated by either alpha-, beta-, or gamma-interferon, but it is not detected in untreated cells. More 67K GBP mRNA is accumulated in the gamma-interferon-treated than in alpha- or beta-interferon-treated fibroblasts. This is consistent with more 67K GBP synthesis found in gamma-interferon-treated fibroblasts.
Forwarding metamorphosis (2013)

In Software Defined Networking (SDN) the control plane is physically separate from the forwarding plane. Control software programs the forwarding plane (e.g., switches and routers) using an open interface, such as OpenFlow. This paper aims to overcomes two limitations in current switching chips and the OpenFlow protocol: i) current hardware switches are quite rigid, allowing ``Match-Action'' processing on only a fixed set of fields, and ii) the OpenFlow specification only defines a limited repertoire of packet processing actions. We propose the RMT (reconfigurable match tables) model, a new RISC-inspired pipelined architecture for switching chips, and we identify the essential minimal set of action primitives to specify how headers are processed in hardware. RMT allows the forwarding plane to be changed in the field without modifying hardware. As in OpenFlow, the programmer can specify multiple match tables of arbitrary width and depth, subject only to an overall resource limit, with each table configurable for matching on arbitrary fields. However, RMT allows the programmer to modify all header fields much more comprehensively than in OpenFlow. Our paper describes the design of a 64 port by 10 Gb/s switch chip implementing the RMT model. Our concrete design demonstrates, contrary to concerns within the community, that flexible OpenFlow hardware switch implementations are feasible at almost no additional cost or power.
The ergogenic supplement β-hydroxy-β-methylbutyrate (HMB) attenuates insulin resistance through suppressing GLUT-2 in rat liver (2015)

This study investigates the effect of the ergogenic supplement β-hydroxy-β-methylbutyrate (HMB) on insulin resistance induced by high-fructose diet (HFD) in rats. Male Sprague Dawley rats were fed 60% HFD for 12 weeks and HMB (320 mg·kg(-1)·day(-1), orally) for 4 weeks. HFD significantly increased fasting insulin, fasting glucose, glycosylated hemoglobin (HBA1C), liver glycogen content, and homeostasis model assessment of insulin resistance (HOMA-IR) index, while it decreased glucose and insulin tolerance. Furthermore, HFD significantly increased serum triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol (VLDL-C) levels, while it significantly decreased high density lipoprotein cholesterol (HDL-C). Moreover, HFD significantly increased mRNA expression of glucose transporter type-2 (GLUT-2), the mammalian target of rapamycin (mTOR), and sterol regulatory element-binding protein-1c (SREBP-1c) but decreased peroxisome proliferator-activated receptor-alpha (PPAR-α) in liver. Aortic relaxation to acetylcholine (ACh) was impaired and histopathology showed severe hepatic steatosis. HMB significantly increased insulin tolerance and decreased fasting insulin, HOMA-IR, HBA1C, hepatic glycogen content, serum TG, LDL-C, and VLDL-C. Additionally, HMB enhanced ACh-induced relaxation, ameliorated hepatic steatosis, and decreased mRNA expression of GLUT-2. In conclusion, HMB may attenuate insulin resistance and hepatic steatosis through inhibiting GLUT-2 in liver.
The influence of Sodium Butyrate on hybridoma proliferation and antibody production (1991)

Using different concentration of sodium butyrate in RPMI 1640-20 or serum-free medium to culture hybridoma cells which secreted monoclonal antibodies (McAbs) against tissue-type plasminogen activator (t-PA). The results indicate that 0.25mmol/L-0. 5mmol/L of sodium butyrate could incite hybridoma cells to produce McAbs and had no inhibition on hybridoma cell growth. The maximum titer of McAb was 1:2500, 2-4 fold more than control. Sodium butyrate may be as an additive to enhance the ability of hybridoma secreting McAbs.
Protective Immune Responses Induced by Vaccination with an Expression Genomic Library of Leishmania major (1999)

To develop an effective vaccine against the intracellular protozoan parasite Leishmania spp., we investigated the feasibility of expression library immunization (ELI) in the mouse. Genomic expression libraries of L. major were constructed and used to immunize mice. One of the three libraries (L1, with 10(5) clones) induced a significant protective immune response and delayed the onset of lesion development in highly susceptible BALB/c mice after i.m. immunization, compared with control mice immunized with the empty vector (EV). L1 was then divided into five sublibraries of approximately 2 x 10(4) clones each. Mice immunized with one of the sublibraries (SL1A) developed an even stronger protective effect than that induced by L1. SL1A was further divided into 20 sublibraries (SL2) of approximately 10(3) clones each. One of the SL2 libraries (SL2G) induced a strong protective effect against L. major infection. In direct comparative studies, the protective effect of the sublibraries was in the order of SL2G > SL1A > L1. Lymphoid cells from mice vaccinated with SL2G produced more IFN-gamma and NO, compared with cells from control mice injected with EV. Serum from the vaccinated mice also contained more parasite-specific IgG2a Ab, compared with controls. Therefore, these data demonstrate that ELI is feasible against this complex intracellular parasitic infection, by preferentially inducing the development of Th1 responses. Furthermore, by sequential division of the libraries, this approach may be used to enrich and identify protective genes for effective gene vaccination against other parasitic infections.
Diastereo- and Enantioselective Synthesis of ∆2-1,2,4-Oxadiazolines by 1,3-Dipolar Cycloaddition of Nitrile Oxides with Chiral Hydrazones (1999)

Diastereo-and enantioselective 1,3-dipolar cycloadditions of nitrile oxides (3) with a,P-unsaturated hydrazones (2) gave spiro oxadiazolines (4) in good yields and low to excellent diastereomeric excesses (de = 5 -298%).Open chain hydrazones (6) afforded 5,5-disubstituted ~2-1,2,4axadiazolines (7).A subsequent N-N bond cleavage to remove the chiral auxiliary was achieved with formic acid and gave the oxadiazolines (8) (ee = 0 -91%).Intermolecular 1,3-dipolar cycloaddition reactions of chiral nitrile oxides usually proceed with moderate control of stereoselectivity.' Possible causes for moderate ratios of diastereomers (usually < 75:25) are the linear dipole, the lack of orientation by complexation and the relatively long distance between the auxiliary and center of reaction.2However, intramolecular stereoselective 1,3-dipolar cycloadditions via nitrile oxides have been successfully carried out, for instance by Takahashi and Iwamoto, generating two key building blocks for the synthesis of taxol derivatives?Further examples of intramolecular diastereoand enantioselective nitrile oxide cycloadditions leading to functionalized cis-decalins 4 or the stereoselective total synthesis of (+)-pumiliotoxin C by Fukumoto et a1.5 have recently been reported.Chiral dipolarophiles have also been used for diastereo-and enantioselective 1,3-dipolar cycloadditions with nitrile oxides.6For example, Carretero et al. successfully utilized a,D-unsaturated sulfones as enantiopure dipolarophiles and opened an efficient entry to functionalized isoxazolines.7Some of the observed diastereoselectivities can he explained with the "inside alkoxy-model" by Houk ef aL8Isoxazolines may also be prepared by a catalytic 1,3-dipolar cycloaddition of nitrile oxides as was reported by Ukaji et 01.9Using equimolar amounts of (R,R)-diisopropyl tartrate in the presence of diethylzinc as catalyst furnished the heterocycles in good yields and ee-values of 84 -93%.We wish now to report our results on diastereo-and enantioselective 1,3-dipolar cycloaddition reactions of nitrile oxides utilizing proline derived hydrazones as enantiopure dipolarophiles.H 37 86 -322.6 -54.1 c C6H5 CH2CHj H 57 86 -333.8 -112.4 d (CH2)2CH3 CH3 CH3 63 96 -276.7 e (CH2)jCHj CH3 CH3 59 71 -217.9 -214.
Activation of Human Polymorphonuclear Leukocytes by Products Derived from the Peroxidation of Human Red Blood Cell Membranes (1998)

Oxidation of red blood cell (RBC) ghost preparations initiated by tert-butyl hydroperoxide (tBuOOH) was employed to explore the formation of lipid products derived from endogenous phospholipids that specifically expressed biological activity toward the human polymorphonuclear leukocyte (PMN). Common measure of lipid peroxidation, thiobarbituric acid-reactive substances (TBARS) and the increased absorbance at 235 nm consistent with the formation of conjugated dienes, was observed following a 90-min incubation of RBC ghosts with tBuOOH. Saponification of phospholipids and separation of the resultant fatty acids by RP-HPLC permitted direct mass spectrometric analysis of oxidized fatty acids. Individual HPLC fractions were assayed for their ability to increase intracellular free calcium ion concentrations in human PMN to guide structural investigations. Two fractions were found to contain biologically active components, and tandem mass spectrometric analysis of the abundant ions observed in these fractions resulted in the characterization of several oxidized polyunsaturated fatty acids derived from arachidonic and linoleic acids. The major components in these fractions included 5-hydroxyeicosatetraenoic acid (5-HETE) and 5-hydroperoxyeicosatetraenoic acid (5-HpETE). The dose-dependent increases in intracellular calcium in the neutrophil using synthetic 5(rac)-HETE, 5(rac)-HpETE, and 5-oxo-ETE were found to have EC50's of 250, 6, and 3 nM, respectively. The quantity of 5-oxygenated arachidonate components present in oxidized RBC was consistent with the observed biological response elicited by fractions A and B. This study suggests that 5-HETE and 5-HpETE are abundant products of lipid peroxidation of cellular membranes and that these racemic products possess significant biological activity. Such compounds could play important roles as mediators of the cellular response to toxicologic stimuli that generate free radical species.