gebhart/patrepeval huggingface dataset:
Peptide Arrays Identify Isoform-Selective Substrates for Profiling Endogenous Lysine Deacetylase Activity (2010)

This paper reports the development of a class of isoform-selective peptide substrates for measuring endogenous lysine deacetylase (KDAC) activities in cell culture. The peptides were first identified by comparing the substrate specificity profiles of the four KDAC isoforms KDAC2, KDAC3, KDAC8, and sirtuin 1 (SIRT1) on a 361-member hexapeptide array wherein the two C-terminal residues to the acetylated lysine were varied. The arrays were prepared by immobilizing the peptides to a self-assembled monolayer of alkanethiolates on gold and could therefore be analyzed by a mass spectrometry technique termed SAMDI (self-assembled monolayers for matrix assisted laser desorption/ionization time-of-flight mass spectrometry). Arrays presenting the selective substrates were treated with nuclear extracts from HeLa, Jurkat, and smooth muscle cells and analyzed to measure endogenous deacetylase activities. We then use the arrays to profile KDAC activity through the HeLa cell cycle. We find that the activity profile of the KDAC3 selective peptide closely mirrors the changing acetylation state of the H4 histone, suggesting a role for this enzyme in cell cycle regulation. This work is significant because it describes a general route for identifying selective substrates that can be used to understand the differential roles of members of the deacetylase enzyme family in complex biological processes and further because the label-free approach avoids perturbation of enzyme activity that has plagued fluorescence-based assays.
Comparison of Common γ-Chain Cytokines, Interleukin-2, Interleukin-7, and Interleukin-15 for the In Vitro Generation of Human Tumor-Reactive T Lymphocytes for Adoptive Cell Transfer Therapy (2006)

The adoptive transfer of human tumor-reactive T lymphocytes into autologous patients can mediate the regression of metastatic melanoma. Here, the in vitro generation of melanoma-reactive T lymphocytes was compared using 3 common gamma-chain cytokines, interleukin (IL)-2, IL-7, and IL-15, alone or in combination. The proliferation, function, and phenotype were evaluated for tumor-reactive T cells derived from peripheral blood mononuclear cells (PBMCs) from patients previously immunized with the melanoma-associated peptide gp100:209-217(210M) and PBMCs transduced with a retrovirus encoding the alpha and beta chains of a gp100-reactive T-cell receptor (TCR). IL-7 alone did not induce significant proliferation of any tumor-reactive T-cell population, whereas IL-2 and IL-15 induced significant proliferation of tumor-reactive T lymphocytes from both sources. Cells cultured in the presence of IL-2 or IL-15 secreted comparable amounts of interferon-gamma and IL-2 in response to melanoma cells in vitro and were phenotypically similar in terms of costimulatory molecules (CD27 and CD28), cytokine receptors (CD25, CD122, and CD127), and a lymphoid homing molecule (CD62L). In addition, the proliferation, function, and phenotype of T cells cultured with combinations of IL-2, IL-7, and IL-15 were similar to those grown with IL-2 alone. The effects of these cytokines on TCR stimulation of CD45RA+ naive cells derived from adult patients and from human umbilical cord blood were also compared. Similar to the data with activated tumor-reactive T lymphocytes, IL-7 alone did not support significant proliferation of naive T cells after TCR stimulation with anti-CD3, although IL-2 and IL-15 induced comparable proliferation of T lymphocytes with similar phenotypic attributes.
Nucleic acid aptamers for targeting of shRNA-based cancer therapeutics. (2007)

Aptamers are nucleic acid ligands which have been validated to bind to epitopes with a specificity similar to that of monoclonal antibodies. Aptamers have been primarily investigated for their direct function in terms of inhibition of protein targets; however, recent evidence gives reason to actively explore aptamers as targeting moieties for delivery of anticancer therapeutics. Many aptamers have been developed to bind to extracellular membrane domains of proteins overexpressed on cancer cells and have the potential to be modified for use in targeting cancer therapeutics. The use of DNA vector-based short hairpin RNA (shRNA) for RNA interference (RNAi) is a precise means for the disruption of target gene expression but its clinical usage in cancer is limited by obstacles related to delivery into cancer cells. Nucleic acid aptamers are attractive candidates for targeting of shRNA therapies. Their small size, ease of production and modification, and high specificity are valued attributes in comparison to other targeting moieties currently being tested. Here we review the development of aptamers directed to PSMA, Nucleolin, HER-3, RET, TN-C, and MUC1 and focus on their potential for use in targeting of shRNA-based cancer therapeutics.
90 Characterisation of an HCV NS3/NS4A proteinase fusion protein expressed in E.coli using synthetic peptide substrates (1997)

Conference Article| November 01 1997 90 Characterisation of an HCV NS3/NS4A proteinase fusion protein expressed in E.coli using synthetic peptide substrates TREVOR C.I. WILKINSON; TREVOR C.I. WILKINSON 1Roche Discovery Welwyn, Broadwater Road, Welwyn Garden City, Herts., AL7 3AY, U.K. Search for other works by this author on: This Site PubMed Google Scholar PETER R. BUNYARD; PETER R. BUNYARD 1Roche Discovery Welwyn, Broadwater Road, Welwyn Garden City, Herts., AL7 3AY, U.K. Search for other works by this author on: This Site PubMed Google Scholar KATHLEEN QUIRK; KATHLEEN QUIRK 1Roche Discovery Welwyn, Broadwater Road, Welwyn Garden City, Herts., AL7 3AY, U.K. Search for other works by this author on: This Site PubMed Google Scholar CLAIRE S. WILKINSON CLAIRE S. WILKINSON 1Roche Discovery Welwyn, Broadwater Road, Welwyn Garden City, Herts., AL7 3AY, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1997) 25 (4): S624. https://doi.org/10.1042/bst025s624 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation TREVOR C.I. WILKINSON, PETER R. BUNYARD, KATHLEEN QUIRK, CLAIRE S. WILKINSON; 90 Characterisation of an HCV NS3/NS4A proteinase fusion protein expressed in E.coli using synthetic peptide substrates. Biochem Soc Trans 1 November 1997; 25 (4): S624. doi: https://doi.org/10.1042/bst025s624 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: DABCYL, 4-(4-dimethylaminophenylazo) benzoic acid, EDANS, 5-[(2-aminoethyl)amino]naphthalene-1-sulphonic acid This content is only available as a PDF. © 1997 Biochemical Society1997 Article PDF first page preview Close Modal You do not currently have access to this content.
Prodrugs of a 1′-CN-4-Aza-7,9-dideazaadenosine C-Nucleoside Leading to the Discovery of Remdesivir (GS-5734) as a Potent Inhibitor of Respiratory Syncytial Virus with Efficacy in the African Green Monkey Model of RSV (2021)

A discovery program targeting respiratory syncytial virus (RSV) identified <i>C</i>-nucleoside <b>4</b> (RSV A2 EC<sub>50</sub> = 530 nM) as a phenotypic screening lead targeting the RSV RNA-dependent RNA polymerase (RdRp). Prodrug exploration resulted in the discovery of remdesivir (<b>1</b>, GS-5734) that is >30-fold more potent than <b>4</b> against RSV in HEp-2 and NHBE cells. Metabolism studies in vitro confirmed the rapid formation of the active triphosphate metabolite, <b>1</b>-<b>NTP</b>, and in vivo studies in cynomolgus and African Green monkeys demonstrated a >10-fold higher lung tissue concentration of <b>1-NTP</b> following molar normalized IV dosing of <b>1</b> compared to that of <b>4</b>. A once daily 10 mg/kg IV administration of <b>1</b> in an African Green monkey RSV model demonstrated a >2-log<sub>10</sub> reduction in the peak lung viral load. These early data following the discovery of <b>1</b> supported its potential as a novel treatment for RSV prior to its development for Ebola and approval for COVID-19 treatment.
Monitoring Cell Signaling Pathways by Quantitative Flow Cytometry (2007)

As the signaling pathways involved in leukemogenesis are being elucidated, several proteins have emerged as potential targets for therapy. Downstream from those targets are numerous intracellular factors that are constantly modulated. Monitoring those factors could provide insight into the potential efficacy of therapies by predicting which patients will respond to them and by determining the optimal dosage that will inhibit the target protein. We describe a flow cytometry method for quantitation of total and phosphorylated intracellular proteins. Compared with Western blot analysis, this technique dramatically decreases time and labor while providing multiparameter information on specific cell populations. As an example, total and phosphorylated CRKL is quantitated. The methodology has the potential for widespread application in the monitoring of targeted therapy.
Einleitung (1997)

Als Umberto Eco 1962 seine Studie über Das offene Kunstwerk veröffentlichte, fügte er dem Text eine Anmerkung bei, aus der schlaglichtartig die weltbildnerische Funktion des Romans erhellt. Diese Anmerkung lautet: »Es ist nur natürlich, daß das Leben mehr dem als den gleicht: dennoch sind wir alle eher geneigt, es in den Kategorien der zu denken als in denen des : oder besser: ich kann das Leben nur erinnern und beurteilen, wenn ich es als traditionellen Roman denke.« (Eco 1977, S. 206).
Currents and vibrations in asynchronous motor with externally induced vibration (2011)

This paper presents an experimental investigation of the airgap variation model for vibration and current harmonics relationship in induction motors. To this aim, an external vibration source was employed, together with ball bearing alterations in order to decrease stiffness. The direction of the external vibration is radial with respect to the axis of the electric machine under test. To maximize the effect of externally induced vibrations, the frequency chosen was near the flexural resonance of the rotor, determined by FEM analysis. During tests both currents and vibration of the machine were acquired. The test rig allowed to vary speed, vibration level and bearing stiffness. An electromagnetic brake provided a variable output load for the electric machine. The focus of the paper is the review of fault models used in literature. Radial effects are usually visible only in case of large failures that result in air-gap variations, as the experiments confirmed.
Learning multiple collaborative tasks with a mixture of Interaction Primitives (2015)

Robots that interact with humans must learn to not only adapt to different human partners but also to new interactions. Such a form of learning can be achieved by demonstrations and imitation. A recently introduced method to learn interactions from demonstrations is the framework of Interaction Primitives. While this framework is limited to represent and generalize a single interaction pattern, in practice, interactions between a human and a robot can consist of many different patterns. To overcome this limitation this paper proposes a Mixture of Interaction Primitives to learn multiple interaction patterns from unlabeled demonstrations. Specifically the proposed method uses Gaussian Mixture Models of Interaction Primitives to model nonlinear correlations between the movements of the different agents. We validate our algorithm with two experiments involving interactive tasks between a human and a lightweight robotic arm. In the first, we compare our proposed method with conventional Interaction Primitives in a toy problem scenario where the robot and the human are not linearly correlated. In the second, we present a proof-of-concept experiment where the robot assists a human in assembling a box.
Rapid, Universal Method to Isolate PCR-Ready DNA Using Magnetic Beads (1997)

A magnetic bead-based system for DNA isolation utilizing monodisperse beads was tested with the aim of producing a general approach for PCR-ready DNA. This commercially available system was originally designed for isolating PCR-ready DNA from human whole blood. We tested diverse organisms belonging to the major groups: bacteria, fungi, algae, vascular plants and vertebrates. Optimization of sample amounts and lysis conditions was done using several types of tissue (fish epithelium, plant leaves, mammalian liver and muscle tissues, fungal fruit-bodies and mycelium). The standard lysis conditions used for blood could be applied with good results for most bacteria, algae and vertebrates, while plant leaves and fungal fruit-bodies had to be mechanically broken to obtain proper lysis. For vascular plants and some cyanobacteria, lysis by heating to 65 degrees C gave better DNA yields than standard lysis at room temperature. In all cases, DNA suitable for PCR was prepared in less than 30 min. The PCR products yielded 350 to 500 bases of DNA sequence (99% accurate) by direct manual or automated sequencing.
Ring Closing Metathesis for the Asymmetric Synthesis of (S)-Homopipecolic Acid, (S)-Homoproline and (S)-Coniine (2002)

Diastereoselective conjugate addition of lithium (S)-N-allyl-N-α-methylbenzylamide to α,β-unsaturated esters or Weinreb amides, followed by ring closing metathesis is used to afford the cyclic β-amino acids (S)-homopipecolic acid and (S)-homoproline and the amine (S)-coniine in high ee.
热阻——何意？如何测量？它给设计者提供何信息？ (2004)

1引言 当今市场上需要占地面积较小且又具有较高功率水平的DC／DC变换器。为了获得这样的功率密度，开关频率提高了，这使MOSFET的功率损耗增加。因而要求设计者对热阻有较好的了解，即何谓热阻?如何测量?它给设计者提供何信息?
Amperometric Glucose Biosensor Based on Immobilization of Glucose Oxidase in Chitosan Matrix Cross-Linked with Glutaraldehyde (2001)

A glucose biosensor was fabricated using chitosan film for the immobilization of glucose oxidase (GOX) and mediator in the following “sandwich” configuration:chitosan-ferrocene:GOX:chitosan using a carbon paste electrode as the basic electrode. To prevent loss of immobilized GOX under optimized conditions, the biosensor surface was cross-linked with glutaraldehyde (GA). Despite the multilayer configuration, the biosensor exhibited a relatively fast response (less than 10 s) and a linear response with glucose in the range of 8×10−4 to 1.7×10−2 M. The biosensor retained about 65 % of its original activity after 30 days of storage in a phosphate buffer at 4 °C. Applicability of the biosensor was demonstrated in real samples and the results obtained by this biosensor corroborate well with a classical UV spectrophotometric technique.
The existence of epithelial-to-mesenchymal cells with the ability to support hematopoiesis in human fetal liver (2005)

The fetal liver is the major hematopoietic organ during mid-gestation, and it is also a source of stem cells that exist in a complex environment. In this study, we isolated a population of actively replicating cells with the characteristic of the epithelial-to-mesenchymal transition (EMT) from fetal liver. These cells were identified with the epithelial markers, including alpha-fetoprotein (AFP), albumin (ALB), cytokeratins (CK) 7, and CK18, as well as the mesenchymal markers, such as alpha-smooth muscle actin (ASMA), CD29, CD44, CD49, CD54, collagen I and osteopontin (OPN). Furthermore, they also expressed some hematopoiesis-related genes. In addition, the cell population had the ability to retain hematopoietic stem cells (HSCs) in an undifferentiated state in vitro during cytokine-stimulated proliferation. These results provide an insight about early human liver development and may also help to understand hematopoiesis in the fetal liver.
Polyoxometalates: Powerful Catalysts for Atom‐Efficient Cyclopropanations (2010)

Abstract The polyoxometalate‐based catalytic cyclopropanation of olefins by ethyl diazoacetate (EDA) is reported. The outstanding catalyst productivity (TONs up to 100,000) and the use of equimolar EDA/olefin ratio confer to the methodology a high sustainability. Preliminary mechanistic investigations are also discussed.
Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities. (1989)

HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes. Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotype. In addition, primarily chronic progressive MS was positively associated with the DQB1 restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQB1 allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQB1 allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers of each clinical form of MS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS. The observed immunogenetic heterogeneity between the different clinical forms of MS favors the hypothesis that primarily chronic progressive MS and relapsing/remitting MS are two distinct disease entities.
Graphene Reknits Its Holes (2012)

Nanoholes, etched under an electron beam at room temperature in single-layer graphene sheets as a result of their interaction with metal impurities, are shown to heal spontaneously by filling up with either nonhexagon, graphene-like, or perfect hexagon 2D structures. Scanning transmission electron microscopy was employed to capture the healing process and study atom-by-atom the regrown structure. A combination of these nanoscale etching and reknitting processes could lead to new graphene tailoring approaches.
Preliminary Assessment of the Tolerance and Efficacy of Florfenicol against Edwardsiella ictaluri Administered in Feed to Channel Catfish (2003)

Abstract A tolerance study was conducted to determine the palatability of florfenicol to channel catfish Ictalurus punctatus. Four tanks of fish (20 fish/tank) were assigned to each of five treatments distinguished by the amount of florfenicol given in feed per kilogram of body weight, namely, 0, 10, 20, 40, or 100 mg. Fish were fed at a rate of 2.5% of body weight per day for 10 consecutive days. On day 11, all surviving fish were euthanatized, counted, and weighed as a group. Florfenicol- medicated feed was palatable to fish at doses of 10, 20, 40, and 100 mg for 10 consecutive days. All 400 fish were necropsied and examined by histopathology, and no treatment-related changes were observed. In a separate exploratory efficacy study, four tanks (20 fish/tank) were assigned to each of the following treatments: (1) not challenged with Edwardsiella ictaluri and fed unmedicated feed, (2) challenged with E. ictaluri and fed unmedicated feed, (3) challenged with E. ictaluri and fed florfenicol at 10 mg per kilogram of body weight, (4) challenged and fed florfenicol at 20 mg/kg, and (5) challenged and fed florfenicol at 40 mg/kg. Treatment was initiated the day after inoculation, and feed was administered by hand for five consecutive days at 2.5% of body weight. The cumulative mortality observed over a 17-d period in treatment groups 1–5 was 2.5, 57.5, 0, 1.25, and 1.25%, respectively. All 400 fish were necropsied and examined by histopathology. The results indicate that florfenicol was effective in controlling mortality from enteric septicemia of catfish with no adverse treatment-related tissue changes. Florfenicol was palatable, safe, and efficacious in controlling mortality due to infection by E. ictaluri in channel catfish.
The effect of feeding salmon oil to sows throughout pregnancy on pre-weaning mortality of piglets (2001)

Abstract Salmon oil (16·5 kg /t), a source of long-chain polyunsaturated n-3 fatty acids, was included in diets offered to multiparous sows during pregnancy and lactation to measure responses in pre-weaning mortality and performance of piglets in two studies. The first study, carried out under commercial conditions, included 196 sows which were offered salmon oil and control diets from immediately post service until weaning. The same diets were also offered to 10 sows per treatment from day 58 of pregnancy in a controlled nutritional study which measured the effects of salmon oil on piglet tissue fatty acid composition. Offering salmon oil to the sow significantly increased gestation length and decreased individual piglet birth weight but had no effect on litter size at birth. Overall, salmon oil reduced pre-weaning mortality from 11·7% to 10·2% mainly by reducing the incidence of deaths from crushing by the sow. More detailed analysis of mortality using a general linear mixed model and 2294 piglet records, demonstrated that the incidence of pre-weaning mortality was significantly decreased with increasing individual piglet birth weight and by inclusion of salmon oil in the diet; the incidence of mortality increased with average piglet birth weight in a litter. Salmon oil inclusion had no effect on weight of litter weaned, sow lactation food intake or subsequent reproductive performance. In both studies, dietary salmon oil increased the proportions of long-chain n-3 polyunsaturated fatty acids in colostrum to a similar extent. In the nutritional study, inclusion of salmon oil reduced the proportions of 20: 4 n-6 in piglet liver and brain at birth and increased the proportions of long-chain n-3 polyunsaturated fatty acids. Therefore, despite reducing piglet birth weight, offering sows salmon oil reduced pre-weaning mortality of piglets. The nutritional study showed that the amount and type of marine oil used may not have been optimal.
Improving RNA-Seq expression estimates by correcting for fragment bias (2011)

The biochemistry of RNA-Seq library preparation results in cDNA fragments that are not uniformly distributed within the transcripts they represent. This non-uniformity must be accounted for when estimating expression levels, and we show how to perform the needed corrections using a likelihood based approach. We find improvements in expression estimates as measured by correlation with independently performed qRT-PCR and show that correction of bias leads to improved replicability of results across libraries and sequencing technologies.
HATs off to Hop: recruitment of a class I histone deacetylase incriminates a novel transcriptional pathway that opposes cardiac hypertrophy (2003)

Histone acetylation, regulated by two antagonistic enzymes — histone acetyltransferases (HATs) and histone deacetylases (HDACs) — results in transcriptional changes and also plays a critical role in cardiac development and disease. A new study shows that overexpression of the atypical transcriptional corepressor homeodomain-only protein (Hop) causes cardiac hypertrophy via recruitment of a class I HDAC. In contrast to the body of work on transcriptional mechanisms that drive cardiac hypertrophy, including class II HDACs, this report elucidates a novel growth-suppressing transcriptional pathway in cardiac muscle that opposes hypertrophic growth.