gebhart/patrepeval huggingface dataset:
Pseudophosphorylation of tau at serine 422 inhibits caspase cleavage: in vitro evidence and implications for tangle formation in vivo (2006)

The tangles of Alzheimer's disease (AD) are comprised of the tau protein displaying numerous alterations, including phosphorylation at serine 422 (S422) and truncation at aspartic acid 421 (D421). Truncation at the latter site appears to result from activation of caspases, a class of proteases that cleave specifically at aspartic acid residues. It has been proposed that phosphorylation at or near caspase cleavage sites could regulate the ability of the protease to cleave at those sites. Here, we use tau pseudophosphorylated at S422 (S422E) to examine the effects of tau phosphorylation on its cleavage by caspase 3. We find that S422E tau is more resistant to proteolysis by caspase 3 than non-pseudophosphorylated tau. Additionally, we use antibodies directed against the phosphorylation site and against the truncation epitope to assess the presence of these epitopes in neurofibrillary tangles in the aged human brain. We show that phosphorylation precedes truncation during tangle maturation. Moreover, the distribution of the two epitopes suggests that a significant length of time (perhaps as much as two decades) elapses between S422 phosphorylation and cleavage at D421. We further conclude that tau phosphorylation at S422 may be a protective mechanism that inhibits cleavage in vivo.
Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor alpha required as a costimulatory factor for interferon gamma-induced activation. (1992)

Interleukin 10 (IL-10) inhibits interferon gamma-induced macrophage activation for cytotoxicity against larvae of the human parasite Schistosoma mansoni by suppressing production of the toxic effector molecule nitric oxide (NO). In this study, the mechanism of IL-10 action was identified as inhibition of endogenous tumor necrosis factor alpha (TNF-alpha) production by interferon gamma-activated macrophages. TNF-alpha appears to serve as a cofactor for interferon gamma-mediated activation, since both schistosomulum killing and NO production were inhibited by anti-TNF-alpha antibody, whereas TNF-alpha alone was unable to stimulate these macrophage functions. IL-10 blocked TNF-alpha production by interferon gamma-treated macrophages at the levels of both protein and mRNA synthesis. Addition of exogenous TNF-alpha reversed IL-10-mediated suppression of macrophage cytotoxic activity as well as NO production. Likewise, addition of a macrophage-triggering agent (bacterial lipopolysaccharide or muramyl dipeptide), which induced the production of TNF-alpha, also reversed the suppressive effect of IL-10 on cytotoxic function. In contrast to IL-10, two other cytokines, IL-4 and transforming growth factor beta, which also inhibit macrophage activation for schistosomulum killing and NO production, did not substantially suppress endogenous TNF-alpha production. These results, therefore, describe a separate pathway by which macrophage microbicidal function is inhibited by the down-regulatory cytokine IL-10.
Insulin rapidly induces the biosynthesis of elongation factor 2 (1989)

Abstract Insulin increases the rate of overall protein synthesis in many cells and tissues, while inducing the preferential expression of individual proteins. To identify and characterize such proteins, NIH 3T3 cells stably expressing more than 10(6) human insulin receptors per cell (HIR 3.5; Whittaker, J., Okamoto, A. K., Thys, R., Bell, G. I., Steiner, D. F., and Hofmann, C. A. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 5237-5241) were treated with insulin in the presence of [35S]methionine, and labeled proteins were separated using ultra-high resolution (giant) two-dimensional gel electrophoresis. Overall protein synthesis was enhanced as much as 3-fold by insulin treatment; the synthesis of approximately 1% of the 2,500 proteins visible on the gel autoradiographs was further selectively increased. By using immunoblotting, immunoprecipitation and comigration assays, we identified one of the rapidly induced proteins (Mr 96,000; pI 6.8) as eukaryotic elongation factor 2 (EF-2), a major component of the protein translation apparatus. Insulin induced the synthesis of EF-2 within 20 min of treatment, with a half-maximal dose of 10(-11) M. It was synthesized as a precursor form that was processed to a more basic mature species within 30 min. Long term treatment with insulin led to accumulation of EF-2 within the cell and prevented the substantial decrease in EF-2 concentration that occurred during serum deprivation. Finally, we found that insulin induction of EF-2 occurred normally in the presence of the RNA-transcription inhibitor, actinomycin D. Thus, insulin rapidly induced the synthesis of EF-2 predominantly or exclusively at the level of mRNA translation.
A model for the RNA-catalyzed replication of RNA. (1986)

A shortened form of the self-splicing ribosomal RNA intervening sequence of Tetrahymena thermophila has enzymatic activity as a poly(cytidylic acid) polymerase [Zaug, A.J. & Cech, T.R. (1986) Science 231, 470-475]. Based on the known properties of this enzyme, a detailed model is developed for the template-dependent synthesis of RNA by an RNA polymerase itself made of RNA. The monomer units for RNA synthesis are tetra- and pentanucleotides of random base sequence. Polymerization occurs in a 5'-to-3' direction, and elongation rates are expected to approach two residues per minute. If the RNA enzyme could use another copy of itself as a template, RNA self-replication could be achieved. Thus, it seems possible that RNA catalysts might have played a part in prebiotic nucleic acid replication, prior to the availability of useful proteins.
Evaluation of technetium-99m-L,L-EC in renal transplant recipients: a comparative study with technetium-99m-MAG3 and iodine-125-OIH. (1994)

The labeling procedure of kit-formulated 99mTc-L,L-EC is easy and efficient. This tracer is safe and suitable for both imaging and quantitative measurement of the renal tubular function. Technetium-99m-L,L-EC represents an excellent alternative to 99mTc-MAG3.
Learning Deconvolution Network for Semantic Segmentation (2015)

We propose a novel semantic segmentation algorithm by learning a deep deconvolution network. We learn the network on top of the convolutional layers adopted from VGG 16-layer net. The deconvolution network is composed of deconvolution and unpooling layers, which identify pixelwise class labels and predict segmentation masks. We apply the trained network to each proposal in an input image, and construct the final semantic segmentation map by combining the results from all proposals in a simple manner. The proposed algorithm mitigates the limitations of the existing methods based on fully convolutional networks by integrating deep deconvolution network and proposal-wise prediction, our segmentation method typically identifies detailed structures and handles objects in multiple scales naturally. Our network demonstrates outstanding performance in PASCAL VOC 2012 dataset, and we achieve the best accuracy (72.5%) among the methods trained without using Microsoft COCO dataset through ensemble with the fully convolutional network.
Microfabricated Devices for Enhanced Bioadhesive Drug Delivery: Attachment to and Small‐Molecule Release Through a Cell Monolayer Under Flow (2009)

The development of a novel microfabricated device for oral drug delivery that overcomes many of the common barriers present in the gastrointestinal tract is reported. Specifically, the attachment of targeting ligands, subsequent device binding, and small molecule release from the microdevices in flow are investigated. A diffusion chamber that permits the simultaneous study of particle binding and small-molecule release under physiologically relevant shear conditions is developed. It is observed that once the particles bind to the cell surface, they remain attached. A small fraction of the devices detach in flow; however, most of these devices readily reattach to the cell layer in a new location. This steady-state density of microdevices is most likely the result of larger order microdevice clusters releasing their loose interactions with nearby microdevices, shifting slightly downstream, and subsequently reattaching to the cell monolayer. The release of a model small molecule from microdevices over time is roughly linear and approximately ten times greater than that observed with the small molecule alone. Overall, the preparation and characterization of an oral drug-delivery microdevice system capable of both targeting and asymmetric release in flow is reported.
Z-Selective Olefin Metathesis Processes Catalyzed by a Molybdenum Hexaisopropylterphenoxide Monopyrrolide Complex (2009)

The molybdenum-based monoaryloxide monopyrrolide (MAP) species, Mo(NAd)(CHCMe(2)Ph)(C(4)H(4)N)(HIPTO) (2a), which contains "small" imido (Ad = 1-adamantyl) and "large" aryloxide (HIPTO = O-2,6(2,4,6-i-Pr(3)C(6)H(2))C(6)H(3)) ligands, catalyzes Z-selective metathesis reactions as a consequence of intermediate metallacyclobutane species not being able to have an (anti) substituent pointing toward the HIPTO group. Ring-opening metathesis polymerization (ROMP) of dicarbomethoxynorbornadiene (DCMNBD) with 2% 2a in toluene leads to >99% cis and >99% syndiotactic poly(DCMNBD), while ROMP of cyclooctene and 1,5-cyclooctadiene (300 equiv) with initiator 2a leads to poly(cyclooctene) and poly(cyclooctadiene) that have cis contents of >99%; all are previously unknown microstructures. Z-Selectivity is also observed in the metathesis of cis-4-octene and cis-3-hexene by initiator 2a to give cis-3-heptene.
BCL‐2 expression by leukaemic blasts in a SCID mouse model of biphenotypic leukaemia associated with the t(4;ll)(q21;q23) translocation (1995)

Acute leukaemia of infancy is associated with abnormalities at chromosome band 11q23, and has a poor prognosis. The gene involved. Mixed Lineage Leukaemia (MLL), has been identified and has the characteristics of a transcription factor. The BCL-2 gene responsible for blocking of programmed cell death is highly expressed in a number of haematological malignancies, both with and without the t(14;18) translocation. Those without the translocation include acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL). In these diseases the BCL-2 protein is implicated in drug resistance to apoptosis-inducing chemotherapeutic agents. High BCL-2 expression is also associated with autonomous growth of leukaemic blasts in culture and predicts a poor prognosis. The SEM cell line, established using blood lymphoblasts from a 5-year-old girl in first relapse with t(4;11) ALL, expresses lymphoid (CD19) and myeloid (CD13) cell surface markers. In cell culture, a subpopulation of cells (< 30%) express the BCL-2 protein. A reproducible model of true biphenotypic leukaemia in the SCID mouse has been established using the SEM-K2 cell line (a subclone of the SEM cell line). Between 5 and 50 million cells injected intravenously (i.v.) produce complete replacement of the murine bone marrow by day 30, associated with blood lymphoblastosis and infiltration of the spleen. No tumour masses were seen. Fluorescence in situ hybridization (FISH) analysis of the cell line and blood from the SCID-human (SCID-hu) chimaera has confirmed the presence of the t(4;11). Reverse transcriptional-polymerase chain reaction (RT-PCR) reveals that the breakpoint lies between exons 7 and 8 of the MLL-1 gene on chromosome 11 (the main breakpoint region). A further translocation, t(7;13), has been identified. Fluorescent antibody cell sorter (FACS) analysis of tumour material recovered from the SCID-hu model confirms expression of CD19 and CD13 identical to that of the cell line. In addition, BCL-2 expression in SCID-hu marrow is now seen in the majority of tumour cells. BCL-2 expression appears to confer a survival advantage to the blast cells in vivo. This reproducible model of biphenotypic leukaemia suggests that BCL-2 expression may play a role in leukaemogenesis. The model is suitable for the investigation of gene-targeted therapy, including antisense oligonucleotides, directed towards the MLL and BCL-2 genes.
ChemInform Abstract: Monolith Structures, Materials, Properties and Uses. (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Leptin receptor‐mediated regulation of cholinergic neurotransmitter phenotype in cells of central nervous system origin (2000)

Leptin is an adipocyte-secreted hormone that regulates body weight and exerts effects on hematopoiesis, reproduction, and immunity. The leptin receptor (OBR) shares sequence similarity and signaling capabilities with receptors for cytokines of the ciliary neurotrophic factor (CNTF) family. Our previous finding that CNTF and leptin exert similar anti-obesity effects and activate common neuronal signaling pathways, prompted us to investigate whether leptin may share with CNTF the ability to regulate the expression of specific neuronal genes. To this end, we established a cell line, derived from the murine septal cholinergic neuronal cell line SN-56, which stably expresses OBR. In this cell line, termed SN-56/OBR, leptin induces STAT transcription factor activation and STAT-dependent reporter gene expression in a manner similar to that of CNTF. Furthermore, in SN-56/OBR cells both CNTF and leptin produce changes in neurotransmitter and neuropeptide phenotype characteristic of cholinergic neurons, such as an increase in choline acetyltransferase and vasoactive intestinal polypeptide, and a decrease in neuropeptide Y expression. SN-56/OBR cells thus constitute an interesting new model system to investigate leptin action in cells of central nervous system origin. Possible physiological implications of OBR's intrinsic ability to regulate cholinergic phenotypic markers are discussed.
NOVARTIS SETS NEW STRATEGY FOR R&D (2002)

RETURN TO ISSUEPREVNewsNEXTNOVARTIS SETS NEW STRATEGY FOR R&DGenomics advances push pharmaceutical company to change how it carries out researchPATRICIA L. SHORTView Author Information C&EN LONDONCite this: Chem. Eng. News 2002, 80, 9, 19–20Publication Date (Print):March 4, 2002Publication History Published online13 November 2010Published inissue 4 March 2002https://pubs.acs.org/doi/10.1021/cen-v080n009.p019https://doi.org/10.1021/cen-v080n009.p019newsACS PublicationsCopyright © 2002 AMERICAN CHEMICAL SOCIETYArticle Views13Altmetric-Citations-LEARN 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 options SUBJECTS:Genomics Get e-Alerts
Abnormal structure and expression of p53 gene in human hepatocellular carcinoma. (1990)

There is little information regarding the molecular mechanisms of hepatocarcinogenesis. We studied the p53 gene at the DNA, RNA, and protein level in seven human hepatocellular carcinoma (HCC)-derived cell lines; six of seven showed p53 abnormalities. By Southern blotting, the p53 gene was found to be partially deleted in Hep 3B and rearranged in SK-HEP-1 cells. Transcripts of the p53 gene were undetectable in Hep 3B as well as in FOCUS cells that had no apparent deletion or rearrangement of the p53 gene. Immunoprecipitation after [35S]methionine labeling of HCC cells demonstrated that p53 protein was absent in Hep 3B and FOCUS and reduced in concentration in PLC/PRF/5 cells. p53 synthesized by Mahlavu cells showed a slower migration on SDS/polyacrylamide gels suggesting it was an abnormal protein. In Huh7 cells, p53 protein had a prolonged half-life leading to its accumulation in the nuclei; increased levels of p53 protein were also found by immunoblotting. The p53 gene and its expression appeared to be unaltered in the hepatoblastoma-derived Hep G2 cell line. We found that the loss of p53 expression did not occur as a late in vitro event in the FOCUS cell line because p53 protein was also nondetectable at an early passage. We conclude that the loss of p53 expression or the presence of abnormal forms of the protein are frequently associated with HCC cell lines. These observations suggest that alterations in p53 may be important events in the transformation of hepatocytes to the malignant phenotype.
A bacterially expressed single-chain Fv construct from the 2B4 T-cell receptor. (1993)

A single-chain Fv construct of the 2B4 T-cell receptor has been made and expressed in Escherichia coli as bacterial inclusion bodies. After solubilization in 6 M guanidine hydrochloride and formation of mixed disulfides with glutathione, the protein was refolded by diluting out the denaturant and allowing intramolecular disulfide bridges to form by disulfide exchange. Approximately 65-100 mg of refolded protein was obtained from 1 liter of bacterial culture, an appreciable fraction of which was monomeric in nondenaturing solvents. This protein bound to three monoclonal antibodies specific for allotypic or idiotypic determinants on the native 2B4 variable region but did not bind several other anti-T-cell-receptor monoclonal antibodies that lacked such specificity. These experiments show that T-cell-receptor variable regions, like the V regions of antibodies, can form a well-behaved single-chain Fv molecule and provide large amounts of recombinant single-chain Fv T-cell receptor that can be used to study T-cell function.
A large-scale car dataset for fine-grained categorization and verification (2015)

This paper aims to highlight vision related tasks centered around “car”, which has been largely neglected by vision community in comparison to other objects. We show that there are still many interesting car-related problems and applications, which are not yet well explored and researched. To facilitate future car-related research, in this paper we present our on-going effort in collecting a large-scale dataset, “CompCars”, that covers not only different car views, but also their different internal and external parts, and rich attributes. Importantly, the dataset is constructed with a cross-modality nature, containing a surveillance-nature set and a web-nature set. We further demonstrate a few important applications exploiting the dataset, namely car model classification, car model verification, and attribute prediction. We also discuss specific challenges of the car-related problems and other potential applications that worth further investigations. The latest dataset can be downloaded at http://mmlab.ie.cuhk.edu.hk/ datasets/comp_cars/index.html.
Optobionic vision—a new genetically enhanced light on retinal prosthesis (2009)

The recent discovery that neurons can be photostimulated via genetic incorporation of artificial opsins is creating a revolution in the field of neural stimulation. In this paper we show its potential in the field of retinal prosthesis. We show that we need typically 100 mW cm(-2) in instantaneous light intensity on the neuron in order to stimulate action potentials. We also show how this can be reduced down to safe levels in order to negate thermal and photochromic damage to the eye. We also describe a gallium nitride LED light source which is also able to generate patterns of the required intensity in order to transfer reliable images.
Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial (2018)

Introduction Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide, used for migraine prevention. Methods A global, double-blind, 6-month study of patients with episodic migraine was undertaken with 915 intent-to-treat patients randomized to monthly galcanezumab 120 mg (n = 231) or 240 mg (n = 223) or placebo (n = 461) subcutaneous injections. Primary endpoint was overall mean change from baseline in monthly migraine headache days. Key secondary endpoints were ≥50%, ≥ 75%, and 100% response rates; monthly migraine headache days with acute migraine medication use; Patient Global Impression of Severity rating; the Role Function-Restrictive score of the Migraine-Specific Quality of Life Questionnaire. Results Mean monthly migraine headache days were reduced by 4.3 and 4.2 days by galcanezumab 120 and 240 mg, respectively, and 2.3 days by placebo. The group differences (95% CIs) versus placebo were 2.0 (-2.6, -1.5) and 1.9 (-2.4, -1.4), respectively. Both doses were superior to placebo for all key secondary endpoints. Injection site pain was the most common treatment-emergent adverse event, reported at similar rates in all treatment groups. Both galcanezumab doses had significantly more injection site reactions and injection site pruritus, and the 240 mg group had significantly more injection site erythema versus placebo. Conclusions Galcanezumab 120 or 240 mg given once monthly was efficacious, safe, and well tolerated. Study identification EVOLVE-2; NCT02614196; https://clinicaltrials.gov/ct2/show/NCT02614196 . Trial Registration NCT02614196.
SYNTHESIS OF 1-ARYLCYCLOPROPANECARBONITRILES UNDER PHASE-TRANSFER CATALYTIC CONDITIONS (1995)

(1995). SYNTHESIS OF 1-ARYLCYCLOPROPANECARBONITRILES UNDER PHASE-TRANSFER CATALYTIC CONDITIONS. Organic Preparations and Procedures International: Vol. 27, No. 3, pp. 355-359.
The design of a similarity based deduplication system (2009)

We describe some of the design choices that were made during the development of a fast, scalable, inline, deduplication device. The system's design goals and how they were achieved are presented. This is the firs deduplication device that uses similarity matching. The paper provides the following original research contributions: we show how similarity signatures can serve in a deduplication scheme; a novel type of similarity signatures is presented and its advantages in the context of deduplication requirements are explained. It is also shown how to combine similarity matching schemes with byte by byte comparison or hash based identity schemes.