gebhart/patrepeval huggingface dataset:
Abstract SY38-03: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia (2012)

Abstract Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia Recurrent chromosomal translocations involving the mixed lineage leukemia (MLL) gene initiate aggressive forms of leukemia, which are often refractory to conventional therapies. Many MLL-fusion partners are members of the super elongation complex (SEC), a critical regulator of transcriptional elongation, suggesting that aberrant control of this process plays an important role in leukemia induction. Here we will describe a global proteomic strategy to demonstrate that MLL-fusions, as part of SEC and the polymerase associated factor (PAFc) complex are associated with the BET family of acetyl-lysine recognising, chromatin “adaptor” proteins. These data provided the basis for therapeutic intervention in MLL-fusion leukemia, via the displacement of the BET family of proteins from chromatin. We will show that a novel small molecule inhibitor of the BET family GSK1210151A (I-BET151) has profound efficacy against human and murine MLL-fusion leukemic cell lines, through the induction of early cell cycle arrest and apoptosis. I-BET151 treatment in two human leukemia cell lines with different MLL-fusions alters the expression of a common set of genes whose function may account for these phenotypic changes. The mode of action of I-BET151 is, at least in part, due to the inhibition of transcription at key genes (BCL2, C-MYC and CDK6) through the displacement of BRD3/4, PAFc and SEC components from chromatin. In vivo studies will demonstrate that I-BET151 has significant therapeutic value, providing survival benefit in two distinct mouse models of murine MLL-AF9 and human MLL-AF4 leukemia. In addition, the efficacy of I-BET151 against human leukemia stem cells (LSC) will be shown, providing further evidence of its potent therapeutic potential. These findings establish the displacement of BET proteins from chromatin as a promising epigenetic therapy for these aggressive leukemias. To extend the applications of our work, we will also present preliminary data to demonstrate that inhibition of BET proteins has therapeutic promise in a larger number of AML subtypes. We will speculate on potential mechanisms for this, the investigation of which is ongoing. Finally, we will discuss extension of the paradigm of BET inhibition to the numerous other epigenetic “readers” implicated in the induction and progression of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY38-03. doi:1538-7445.AM2012-SY38-03
Evaluation of a Public Open Space Depending on User Behaviour in the Post Occupancy Phase (2014)

This study analysed the evaluation of a public open space based on user behaviour in the occupancy phase. The study further analysed to what extent the design projects prepared for the study area satisfied the needs of the users in the post occupancy, and the methods of behavioural observations, environmental measurements and interviews were used in the study. Behaviour observations were performed on a total of 7.896 users in 9 sub - spaces, for a period of nine days between the dates of 18 April - 15 May in Izmir Konak Square. The temperature, humidity and wind strength in the area concerning on the observation days was recorded on the commencement of each observation period. This information revealed the relationship between climatic data and user behaviour. The study was completed with the interviews made with designer and implementing firms. It was found that the space brings together people from every age group and different social groups; the space is mostly used for shopping, socio - cultural activities, transit, short - term relaxation, meeting, gathering and dining and although limited, it offered the users the opportunity of coming together. Unlike what was expected, it was found that the space was not alive for 24 hours
Fucosylation of serum glycoproteins in lung cancer patients (2005)

Increased expression of sialyl Lewis X or A antigens on metastatic cancer cells leads to their selectin-mediated extravasation. Profound fucosylation of the serum microenvironment may be a factor that interrupts adhesion and influences the formation of metastases. In this study we quantitatively analyzed fucosylation of serum glycoproteins in small-cell and non-small-cell lung cancer patients. Fucosylation of four chosen glycoprotein bands was measured as the reactivity with Aleuria aurantia lectin on nitrocellulose blots, preceded by polyacrylamide gel electrophoresis. Relative fucosylation and fucosylation coefficients were calculated by densitometric analysis. Fucosylated oligosaccharides were observed in higher amounts in cancer sera when compared to sera from healthy individuals in all bands analyzed. Glycoproteins of a molecular mass of 29 kDa appear to carry more fucose residues than the 42-kDa band, comprising alpha(1)-acid glycoprotein and haptoglobin. Glycans of the 26-kDa band were fucosylated to a higher extent in non-small-cell vs. small-cell lung cancer. The results suggest that the extent of fucosylation could be a useful marker for estimation of the glycosylation status of serum proteins in cancer patients. Cluster analysis leads to the preliminary suggestion that the fucosylation status could serve as a predictive factor for patient survival.
Genome‐wide search for genes affecting the risk for alcohol dependence (1998)

Alcohol dependence is a leading cause of morbidity and premature death. Several lines of evidence suggest a substantial genetic component to the risk for alcoholism: sibs of alcoholic probands have a 3–8 fold increased risk of also developing alcoholism, and twin heritability estimates of 50–60% are reported by contemporary studies of twins. We report on the results of a six-center collaborative study to identify susceptibility loci for alcohol dependence. A genome-wide screen examined 291 markers in 987 individuals from 105 families. Two-point and multipoint nonparametric linkage analyses were performed to detect susceptibility loci for alcohol dependence. Multipoint methods provided the strongest suggestions of linkage with susceptibility loci for alcohol dependence on chromosomes 1 and 7, and more modest evidence for a locus on chromosome 2. In addition, there was suggestive evidence for a protective locus on chromosome 4 near the alcohol dehydrogenase genes, for which protective effects have been reported in Asian populations. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:207–215, 1998. © 1998 Wiley-Liss, Inc.
Prediction of aqueous solubility of drugs and pesticides with COSMO‐RS (2001)

The COSMO-RS method, originally developed for the prediction of liquid-liquid and liquid-vapor equilibrium constants based on quantum chemical calculations, has been extended to solid compounds by addition of a heuristic expression for the Gibbs free energy of fusion. By this addition, COSMO-RS is now capable of a priori prediction of aqueous solubilities of a wide range of typical neutral drug and pesticide compounds. Only three parameters in the heuristic expression have been fitted on a data set of 150 drug-like compounds. On these data an rms deviation of 0.66 log-units was achieved. Later, the model was tested on a set of 107 pesticides, which have been critically selected based on two experimental data sources and by a crosscheck with an independent HQSAR model. On this data set an rms of 0.61 log-units was achieved, without any adjustments to the structurally extremely diverse pesticides. This result verifies the ability of this extended COSMO-RS to predict aqueous solubilities of drugs and pesticides of almost arbitrary structural classes. The new method is COSMO-RSol.
Capture and analysis of quantitative proteomic data (2007)

Whilst the array of techniques available for quantitative proteomics continues to grow, the attendant bioinformatic software tools are similarly expanding in number. The data capture and analysis of such quantitative data is obviously crucial to the experiment and the methods used to process it will critically affect the quality of the data obtained. These tools must deal with a variety of issues, including identification of labelled and unlabelled peptide species, location of the corresponding MS scans in the experiment, construction of representative ion chromatograms, location of the true peptide ion chromatogram start and end, elimination of background signal in the mass spectrum and chromatogram and calculation of both peptide and protein ratios/abundances. A variety of tools and approaches are available, in part restricted by the nature of the experiment to be performed and available instrumentation. Currently, although there is no single consensus on precisely how to calculate protein and peptide abundances, many common themes have emerged which identify and reduce many of the key sources of error. These issues will be discussed, along with those relating to deposition of quantitative data. At present, mature data standards for quantitative proteomics are not yet available, although formats are beginning to emerge.
Stimulation of Tumor Cell Motility Linked to Phosphodiesterase Catalytic Site of Autotaxin (1996)

A family of extracellular type I phosphodiesterases has recently been isolated by cDNA cloning, but a physiological function linked to the phosphodiesterase active site has remained unknown. We now present evidence that the phosphodiesterase catalytic site, 201YMRPVYPTKTFPN213, is essential for the motility stimulating activity of autotaxin (ATX), one member of the exophosphodiesterase family. Native ATX possesses phosphodiesterase activity at neutral and alkaline pH, binds ATP noncovalently, and undergoes threonine phosphorylation. Homogeneously purified recombinant ATX, based on the teratocarcinoma sequence, retains these same activities. A single amino acid in the phosphodiesterase catalytic site, Thr210, is found to be necessary for motility stimulation, phosphodiesterase activity, and phosphorylation. Two mutant recombinant proteins, Ala210- and Asp210-ATX, lack motility stimulation and lack both enzymatic activities; Ser210-ATX possesses intermediate activities. Another mutation, with the adjacent lysine (Lys209) changed to Leu209-ATX, possesses normal motility stimulation with sustained phosphodiesterase activity but exhibits no detectable phosphorylation. This mutation eliminates the phosphorylation reaction and indicates that the dephosphorylated state is an active motility-stimulating form of the ATX molecule. By demonstrating that the phosphodiesterase enzymatic site is linked to motility stimulation, these data reveal a novel role for this family of exo/ecto-enzymes and open up the possibility of extracellular enzymatic cascades as a regulatory mechanism for cellular motility.
Rapid Progression of Basal-Type Breast Cancer (2007)

This 33-year-old woman with a BRCA1mutation had an enhancing lesion on MRI. Biopsies showed no evidence of cancer. One year later there was a large, invasive carcinoma.
Do mtDNA deletions drive premature aging in mtDNA mutator mice? (2009)

Deletions in mitochondrial DNA (mtDNA) have long been suspected to be involved in mammalian aging, but their role remains controversial. Recent research has demonstrated that relatively higher levels of mtDNA deletions correlate with premature aging in mtDNA mutator mice, which led to the conclusion that premature aging in these mice is driven by mtDNA deletions. However, it is reported here that the absolute level of deletions in mutator mice is quite low, especially when compared with the level of point mutations in these mice. It is thus argued that the available data are insufficient to conclude that mtDNA mutations drive premature aging in mtDNA mutator mice. It remains possible that clonal expansion of mtDNA deletions may result in sufficiently high levels to play a role in age-related dysfunction in some cells, but assessing this possibility will require studies of the distribution of these deletions among different cell types and in individual cells.
Chromosomal assignment of a gene encoding a new collagen type (COL15A1) to 9q21 → q22 (1992)

The collagens constitute a large family of extracellular matrix components primarily responsible for maintaining the structure and biological integrity of connective tissue. These proteins exhibit considerable diversity size, sequence, tissue distribution, and molecular composition. Fourteen types of homo- and/or heterotrimeric molecules, thus far reported, are encoded by a minimum of 27 genes. Nineteen of these genes, including several that are closely linked, have been assigned to 10 separate autosomes, and one collagen gene has been mapped to the X chromosome. We have isolated a 2.1-kb human cDNA clone coding for a collagen molecule different in sequence and structure from types I-XIV collagens. This polypeptide has been designated the alpha 1 chain of type XV collagen. To determine the location of the corresponding gene, the cDNA clone was hybridized to rodent-human hybrid DNAs and to human metaphase chromosomes. The results obtained using the hybrid cell lines showed that this newly identified collagen gene, COL15A1, is present in the pter --> q34 region of chromosome 9. In situ hybridization allowed sublocalization to 9q21 --> q22, a region to which no other collagen genes had previously been assigned. Our data further demonstrate the complex arrangement of the many collagen genes in the human genome.
Structural Determinants of Opioid Activity in Derivatives of 14-Aminomorphinones:  Effects of Changes to the Chain Linking of the C14-Amino Group to the Aryl Ring (2006)

The 14-aminodihydromorphinone and codeinone series of opioid ligands have produced a number of ligands of substantial interest. To investigate the importance of the 14-substituent, a series of analogues in which the side chain length is varied and the amide and alkene functions are reduced have been prepared. Binding affinity, particularly at the mu-opioid receptor (MOR), was largely determined by the aromatic group of the side chain. In the [35S]GTPgammaS functional assay, the ligands having a three-carbon side chain were more potent antagonists than their longer chain counterparts, while shorter, two-carbon chain analogues were of higher MOR efficacy, an effect that was confirmed in vivo. Wash-resistant binding was observed within this series and appeared to be unrelated to side-chain length.
[Expression and significance of PTEN/PI3K signal transduction-related proteins in non-small cell lung cancer]. (2006)

Overexpression of IGF-1R and PI3K, and low expression of PTEN are closely correlated to the development, invasion and metastasis of NSCLC.
Protein design to understand peptide ligand recognition by tetratricopeptide repeat proteins (2004)

Protein design aims to understand the fundamentals of protein structure by creating novel proteins with pre-specified folds. An equally important goal is to understand protein function by creating novel proteins with pre-specified activities. Here we describe the design and characterization of a tetratricopeptide (TPR) protein, which binds to the C-terminal peptide of the eukaryotic chaperone Hsp90. The design emphasizes the importance of both direct, short-range protein-peptide interactions and of long-range electrostatic optimization. We demonstrate that the designed protein binds specifically to the desired peptide and discriminates between it and the similar C-terminal peptide of Hsp70.
A Mobile Food Intake Monitoring System based on Breathing Signal Analysis (2013)

This paper presents a mobile food intake monitoring system. The system works based on a key observation that a person’s otherwise continuous breathing signal is interrupted by a short apnea during swallowing. The breathing signal is collected using two Respiratory Inductance Plethysmography (RIP) be
A Fluorescent Zinc Probe Based on Metal-Induced Peptide Folding (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Fluorescent Zinc Probe Based on Metal-Induced Peptide FoldingHilary Arnold Godwin and Jeremy M. BergView Author Information Department of Biophysics and Biophysical Chemistry Johns Hopkins University School of Medicine 725 N. Wolfe Street, Baltimore, Maryland 21205-2185 Cite this: J. Am. Chem. Soc. 1996, 118, 27, 6514–6515Publication Date (Web):July 10, 1996Publication History Received10 April 1996Published online10 July 1996Published inissue 1 January 1996https://doi.org/10.1021/ja961184dCopyright © 1996 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1178Altmetric-Citations137LEARN 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 InReddit Read OnlinePDF (135 KB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Dyes and pigments,Fluorescence,Peptides and proteins,Probes,Zinc Get e-Alerts
Androgens and Erythropoiesis (1973)

SINCE early investigations exploring the role of sex hormones on the red cell, hemoglobin and hematocrit,1 , 2 numerous reports have now firmly established that androgens stimulate erythropoiesis. Administration of androgens to a variety of mammals and fowl has increased the reticulocyte count, hemoglobin and bone-marrow erythropoietic activity.3 4 5 Conversely, castration of the adult male in the same species results in a definite decrease in the peripheral red-cell count and hemoglobin concentration.3 , 5 6 7 8 The anemia in castrated male animals is restored to normal by administration of androgens.3 , 4 , 7 , 8 In man, repeated observations have shown that the adult male has higher hemoglobin, hematocrit and red-cell count . . .
Synthesis of Enantiomerically Enriched Propargylamines by Copper‐Catalyzed Addition of Alkynes to Enamines (2003)

Abstract The first copper( I ) bromide/Quinap‐catalyzed synthesis of enantiomerically enriched propargylamines by addition of alkynes to enamines is reported. Various functionalized terminal alkynes add smoothly to Nprotected enamines to afford the corresponding amines in good to high yields and moderate to good enantiomeric excesses. The influence of the metal salt, the ligand, and the protecting group on the conversion, the reaction rate, and the stereoselectivity of the reaction are investigated. The scope of the reaction and further transformations of the resulting propargylamines (deprotection, Pauson–Khand reaction) are also described.
Identification of mitogen‐activated protein kinase‐activated protein kinase‐2 as a vimentin kinase activated by okadaic acid in 9L rat brain tumor cells (1998)

Organization of intermediate filament, a major component of cytoskeleton, is regulated by protein phosphorylation/dephosphorylation, which is a dynamic process governed by a balance between the activities of involved protein kinases and phosphatases. Blocking dephosphorylation by protein phosphatase inhibitors such as okadaic acid (OA) leads to an apparent activation of protein kinase(s) and to genuine activation of phosphatase-regulated protein kinase(s). Treatment of 9L rat brain tumor cells with OA results in a drastically increased phosphorylation of vimentin, an intermediate filament protein. In-gel renaturing assays and in vitro kinase assays using vimentin as the exogenous substrate indicate that certain protein kinase(s) is activated in OA-treated cells. With specific protein kinase inhibitors, we show the possible involvement of the cdc2 kinase- and p38 mitogen-activated protein kinase (p38MAPK)-mediated pathways in this process. Subsequent in vitro assays demonstrate that vimentin may serve as an excellent substrate for MAPK-activated protein kinase-2 (MAPKAPK-2), the downstream effector of p38MAPK, and that MAPKAPK-2 is activated with OA treatment. Comparative analysis of tryptic phosphopeptide maps also indicates that corresponding phosphopeptides emerged in vimentin from OA-treated cells and were phosphorylated by MAPKAPK-2. Taken together, the results clearly demonstrate that MAPKAPK-2 may function as a vimentin kinase in vitro and in vivo. These findings shed new light on the possible involvement of the p38MAPK signaling cascade, via MAPKAPK-2, in the maintenance of integrity and possible physiological regulation of intermediate filaments. J. Cell. Biochem. 71:169–181, 1998. © 1998 Wiley-Liss, Inc.
Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy (2002)

Ten percent of newly diagnosed myeloma patients treated with any type of chemotherapy develop deep venous thrombosis (DVT). Thalidomide has proven activity in refractory multiple myeloma (MM), and although single-agent thalidomide has minimal prothrombogenic activity, its combination with cytotoxic chemotherapy is associated with a significantly increased risk of DVT. We analyzed the incidence of DVT in 232 MM patients who received a combination of chemotherapy and thalidomide on 2 protocols that differed only by the inclusion of doxorubicin in one. DT-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide) was offered to patients with preceding standard dose therapy, but no prior autotransplantation, while DCEP-T (dexamethasone/cyclophosphamide/etoposide/cisplatin/thalidomide) was administered for relapse after transplantation. If there were signs or symptoms suggestive of DVT, patients received additional investigations, including Doppler ultrasonography, followed by venography if indicated. Only patients on DT-PACE but not DCEP-T experienced an increased incidence of DVT. A statistical association between the incidence of DVT and combination chemotherapy including doxorubicin (P =.02) was observed; this association was confirmed on multivariate analysis. MM patients treated with thalidomide and doxorubicin have a high risk of developing DVT.
Anaerobic fermentation balance of Escherichia coli as observed by in vivo nuclear magnetic resonance spectroscopy (1989)

Fermenting anaerobic cultures of Escherichia coli were observed by the nonintrusive technique of in vivo, whole-culture nuclear magnetic resonance. Fermentation balances were calculated for hexoses, pentoses, sugar alcohols, and sugar acids. Substrates more reduced than glucose yielded more of the highly reduced fermentation product ethanol, whereas more-oxidized substrates produced more of the less-reduced fermentation product acetate. These relationships were made more obvious by the introduction of ldhA mutations, which abolished lactate production, and delta frd mutations, which eliminated succinate. When grown anaerobically on sugar alcohols such as sorbitol, E. coli produced ethanol in excess of the amount calculated by the standard fermentation pathways. Reducing equivalents must be recycled from formate to account for this excess of ethanol. In mutants deficient in hydrogenase (hydB), ethanol production from sorbitol was greatly decreased, implying that hydrogen gas released from formate by the formate-hydrogen lyase system may be partially recycled, in the wild type, to increase the yield of the highly reduced fermentation product ethanol.