gebhart/patrepeval huggingface dataset:
Copper–Nitrene Complexes in Catalytic CH Amination (2008)

Hydrocarbons activate! Isolable β-diketiminato dicopper–nitrene complexes such as 1 derived from the reaction of [{(Cl2NN)Cu}2(μ-benzene)] and 1-adamantylazide are potent towards nitrene insertion into unactivated sp3-hybridized CH bonds. 1 allows stoichiometric and catalytic intermolecular CH amination of hydrocarbons to give secondary amines (see scheme). Catalyst loadings as low as 0.05 mol % may be used. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Expression of human DNA topoisomerase I in yeast cells lacking yeast DNA topoisomerase I: restoration of sensitivity of the cells to the antitumor drug camptothecin. (1989)

Yeast Saccharomyces cerevisiae strains that are permeable to the antitumor alkaloid camptothecin are killed by the drug if they express DNA topoisomerase I, the cellular target of the drug (J. Nitiss and J.C. Wang, Proc. Natl. Acad. Sci. USA, 85: 7501-7505, 1988). We show that in a yeast strain permeable to camptothecin but lacking DNA topoisomerase I, sensitivity to the drug was restored upon expression of human DNA topoisomerase I from a plasmid-borne human complementary DNA clone. When the human enzyme was expressed from a galactose-inducible, glucose-repressible yeast promoter, PGAL1, sensitivity to camptothecin was observed in the presence of galactose but not in the presence of glucose. Expression of human DNA topoisomerase I in Escherichia coli was also demonstrated by the complementation of a conditional lethal E. coli DNA topoisomerase I mutant. These systems can be used in the study of human DNA topoisomerase I-camptothecin interactions and in the screening of additional therapeutics targeting the enzyme.
Modulation of Ras and a-Factor Function by Carboxyl-Terminal Proteolysis (1997)

Prenylated proteins contain a covalently linked cholesterol intermediate near their carboxyl-termini. Maturation of most prenylated proteins involves proteolytic removal of the last three amino acids. Two genes in Saccharomyces cerevisiae, RCE1 and AFC1, were identified that appear to be responsible for this processing. The Afc1 protein is a zinc protease that participates in the processing of yeast a-factor mating pheromone. The Rce1 protein contributes to the processing of both Ras protein and a-factor. Deletion of both AFC1 and RCE1 resulted in the loss of proteolytic processing of prenylated proteins. Disruption of RCE1 led to defects in Ras localization and signaling and suppressed the activated phenotype associated with the allele RAS2val19.
An Automated Model to Identify Heart Failure Patients at Risk for 30-Day Readmission or Death Using Electronic Medical Record Data (2010)

Clinical and social factors available within hours of hospital presentation and extractable from an EMR predicted mortality and readmission at 30 days. Incorporating complex social factors increased the model's accuracy, suggesting that such factors could enhance risk adjustment models designed to compare hospital readmission rates.
A computer model of the interleukin‐4/receptor complex (1993)

Interleukin-4 is a member of the cytokine family, a group of related messenger proteins which collectively help to moderate and control the immune response. It is believed that the folding topology of the beta-sheets of the interleukin-4 receptor (IL4R) is the same as that seen in the crystal structure of CD4. Although the sequence identity is low, homology modeling techniques have been used to model the IL4R structure from CD4. Refinement by molecular dynamics leads to a suggested structure which has been docked to interleukin-4 (IL4). Several residues of apparent importance for binding are identified.
The clinical impact and molecular biology of del(17p) in multiple myeloma treated with conventional or thalidomide‐based therapy (2011)

Hemizygous deletion of 17p (del(17p)) has been identified as a variable associated with poor prognosis in myeloma, although its impact in the context of thalidomide therapy is not well described. The clinical outcome of 85 myeloma patients with del(17p) treated in a clinical trial incorporating both conventional and thalidomide-based induction therapies was examined. The clinical impact of deletion, low expression, and mutation of TP53 was also determined. Patients with del(17p) did not have inferior response rates compared to patients without del(17p), but, despite this, del(17p) was associated with impaired overall survival (OS) (median OS 26.6 vs. 48.5 months, P < 0.001). Within the del(17p) group, thalidomide induction therapy was associated with improved response rates compared to conventional therapy, but there was no impact on OS. Thalidomide maintenance was associated with impaired OS, although our analysis suggests that this effect may have been due to confounding variables. A minimally deleted region on 17p13.1 involving 17 genes was identified, of which only TP53 and SAT2 were underexpressed. TP53 was mutated in <1% in patients without del(17p) and in 27% of patients with del(17p). The higher TP53 mutation rate in samples with del(17p) suggests a role for TP53 in these clinical outcomes. In conclusion, del(17p) defined a patient group associated with short survival in myeloma, and although thalidomide induction therapy was associated with improved response rates, it did not impact OS, suggesting that alternative therapeutic strategies are required for this group.
Translation of 2′-modified mRNAin vitroandin vivo (1994)

2'-Fluoro- and 2'-amino-2'-deoxynucleoside triphosphates have been used for in vitro transcription of 2'-modified luciferase mRNA. The 2'-modified deoxynucleoside-containing transcripts were tested for the expression of luciferase in X.Laevis oocytes as well as in rabbit reticulocyte lysate. Only 2'-fluoro-2'-deoxy-adenosine-modified mRNA gave rise to luciferase as shown by SDS gel as well as by enzyme activity measurements in vivo as well as in vitro. 2'-Fluoro-2'-deoxy-pyrimidine nucleoside-modified mRNA did not give rise to luciferase activity. However, they directed incorporation of 35S-labeled methionine into peptide fragments in rabbit reticulocyte lysate indicating premature termination of translation. No or only extremely little of such incorporation could be detected with 2'-amino modified transcripts.
Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine (1999)

Cyclin-dependent kinase (cdk) inhibitors, such as p16(INK4a) and p21(WAF1/CIP1), often inhibit G(1) cyclin kinases and result in G(1) arrest. It has been suggested that p21(WAF1/CIP1) may also play a role in other chemopreventive activities such as DNA repair, slowdown of DNA replication and induction of cellular differentiation. In this report we demonstrate that the antioxidant N-acetylcysteine (NAC), a well-known chemopreventive agent, induces p16(INK4a) and p21(WAF1/CIP1) gene expression and prolongs cell-cycle transition through G(1) phase. A portion of the G(1) arrest by NAC is governed by p16(INK4a); it is independent of p53. NAC's usual mechanism of increasing intracellular glutathione level is not required for the G(1) arrest. An antioxidant whose action is limited to scavenging radicals, Trolox, does not induce G(1) arrest. Taken together, these results suggest a potential novel molecular basis for chemoprevention by NAC.
Charcot-Marie-Tooth Disease Type 1A -- Association with a Spontaneous Point Mutation in the PMP22 Gene (1993)

The PMP22 gene has a causative role in CMT type 1. Either a point mutation in PMP22 or a duplication of the region including the PMP22 gene can result in the disease phenotype.
Cloning, nucleotide sequence, and characterization of genes encoding the secretion function of the Pasteurella haemolytica leukotoxin determinant (1989)

The structural gene of the Pasteurella haemolytica leukotoxin determinant is highly homologous to that of the Escherichia coli hemolysin determinant, which also encodes a specialized set of genes involved in the secretion of the hemolysin. In this report, we describe the cloning and nucleotide sequence of the analogous secretion genes from P. haemolytica which make up the remainder of the leukotoxin determinant. The secretion genes were cloned directly from the P. haemolytica chromosome to form the recombinant plasmid pPH5B. By subcloning the secretion genes together with the leukotoxin structural gene, the cloned leukotoxin determinant was reconstructed on a single plasmid, pLKT52, which directs the synthesis of active leukotoxin to the culture supernatant when expressed in E. coli. DNA sequence analysis showed the presence of two secretion genes, designated lktB and lktD in order of their genetic organization, which code for proteins of 79.7 and 54.7 kilodaltons, both of which were detected when pLKT52 was expressed in E. coli minicells. The lktB and lktD genes were found to be highly homologous to the hlyB and hlyD secretion genes of the hemolysin determinant, and the predicted LktB-HlyB and LktD-HlyD proteins were 90.5 and 75.6% homologous. Nucleotide sequence homology between the leukotoxin and hemolysin determinants was limited to the C, A, B, and D coding regions, although the presence of similar transcriptional terminators in the A-B intercistronic region is suggestive of a similar transcriptional organization. On the basis of these data, we hypothesize that the two determinants share a common evolutionary history and are prototypes for a widely disseminated family of virulence factors, the RTX cytotoxins.
Expression of Mouse Proopiomelanocortin in an Insulinoma Cell Line (1989)

Proopiomelanocortin (POMC) is a neuroendocrine precursor protein which is processed at paired basic amino acids in a tissue-specific manner. To study this phenomenon, a vaccinia virus recombinant, which directs the synthesis of mouse POMC (VV:mPOMC) was constructed and used to infect epithelial (BSC-40) and endocrine (Rin m5F) cell lines. Bona fide mPOMC was produced in both cell types and beta-endorphin immunoreactivity was secreted in a nonregulated manner from BSC-40 cells and in a regulated manner from Rin m5F cells. Although the precursor was not cleaved to smaller beta-MSH or beta-endorphin immunoreactive peptides in BSC-40 cell extracts, Rin m5F cells produced primarily authentic gamma-lipotropin and des-acetyl beta-endorphin. Furthermore, production of these peptides was restricted to the regulated secretory pathway in Rin m5F cells. Site-directed mutagenesis was then used to change the inefficiently recognized Lys-Lys potential cleavage site near the carboxyl terminus of beta-endorphin to Lys-Arg. Expression of the mutant precursor in Rin m5F cells resulted in the synthesis of both des-acetyl beta-endorphin and beta-endorphin.
Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1 beta. (1991)

The three-dimensional structure of the 146-residue form of human basic fibroblast growth factor (bFGF), expressed as a recombinant protein in yeast, has been determined by x-ray crystallography to a resolution of 1.8 A. bFGF is composed entirely of beta-sheet structure, comprising a three-fold repeat of a four-stranded antiparallel beta-meander. The topology of bFGF is identical to that of interleukin 1 beta, showing that although the two proteins share only 10% sequence identity, bFGF, interleukin 1, and their homologs comprise a family of structurally related mitogenic factors. Analysis of the three-dimensional structure in light of functional studies of bFGF suggests that the receptor binding site and the positively charged heparin binding site correspond to adjacent but separate loci on the beta-barrel.
What Macromolecular Crowding Can Do to a Protein (2014)

The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the "real life" situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model "crowding agents". Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area.
Production of luciferase-magnetic particle complex by recombinantMagnetospirillum sp. AMB-1 (2000)

Luciferase-bacterial magnetic particle (BMP) complexes were produced by recombinant Magnetospirillum sp. AMB-1. We constructed plasmids pKML and pNELM, respectively, by fusing luc to the 5' and 3' terminal of magA, encoding an integral iron translocating protein situated in the BMP membrane, of AMB-1. In addition, we produced bifunctional active-fusion proteins on BMPs by using a plasmid pAcML. In this plasmid, acetate kinase and luciferase genes were fused to the N-terminus and the C-terminus of MagA, respectively. Bacterial magnetic particles isolated from transconjugants for pKML, pNELM and pAcML exhibited luciferase activity. Bacterial magnetic particles isolated from transconjugants for pAcML also exhibited acetate kinase activity. Fed-batch culture of pKML transconjugant yielded 2.6 mg BMPs per liter of culture, and 95% conversion of iron into magnetite was obtained, at a nitrate concentration of 1.4 mM. Continuous feeding of iron as ferric quinate significantly enhanced growth and total magnetic production. Final cell concentration of 1.8 x 10(9) cells/mL and 6 mg per liter of culture was obtained. Magnetite production by fed-batch culture of AMB-1 was about 3 times that obtained by batch culture. There were no significant differences in BMPs yield between recombinant AMB-1 cultivated by fed-batch culture and wild type of AMB-1.
Kinetics of Metastatic Breast Cancer Cell Trafficking in Bone (2006)

Early arrest in metaphysis and minimal retention in diaphysis highlight the importance of the local milieu in determining metastatic potential. These results extend the Seed and Soil hypothesis by demonstrating both intertissue and intratissue differences governing metastatic location. Ours is the first in vivo evidence that tumor cells influence not only osteoclasts, as widely believed, but also eliminate functional osteoblasts, thereby restructuring the bone microenvironment to favor osteolysis. The data may also explain why patients receiving bisphosphonates fail to heal bone despite inhibiting resorption, implying that concurrent strategies that restore osteoblast function are needed to effectively treat osteolytic bone metastases.
Obinutuzumab induces superior B-cell cytotoxicity to rituximab in rheumatoid arthritis and systemic lupus erythematosus patient samples (2017)

Taken together, these data provide a mechanistic basis for resistance to rituximab-induced B-cell depletion, and for considering obinutuzumab as an alternative B-cell depleting agent in RA and SLE.
Characteristics of Zn-Al-Cu Alloys for High Temperature Solder Application (2008)

Melting range, microstructure, mechanical properties and spreadabililty of Zn-(4∼6 mass%)Al-(1∼6 mass%)Cu alloys were investigated. Liquidus temperature was targeted between 655 and 675 K, and solidus temperature was targeted to 645 K. The liquidus temperature of the Zn-Al-Cu solders increased with Cu contents, but it decreased with Al contents. Microstructures of the Zn-Al-Cu solders consisted of primary ε-phase (CuZn4), η-phase (Zn matrix), α-η eutectic phase (Zn-Al eutectic) and ε-η eutectic phase (Zn-Cu eutectic), irrespective of the Al and Cu contents. Increasing the Al and Cu contents, hardness and tensile strength increased, but elongation decreased. The Al content played an important role in improving the spread ratio, the Cu content had no significant influence on the spread ratio.
Deep GrabCut for Object Selection (2017)

Most previous bounding-box-based segmentation methods assume the bounding box tightly covers the object of interest. However it is common that a rectangle input could be too large or too small. In this paper, we propose a novel segmentation approach that uses a rectangle as a soft constraint by transforming it into an Euclidean distance map. A convolutional encoder-decoder network is trained end-to-end by concatenating images with these distance maps as inputs and predicting the object masks as outputs. Our approach gets accurate segmentation results given sloppy rectangles while being general for both interactive segmentation and instance segmentation. We show our network extends to curve-based input without retraining. We further apply our network to instance-level semantic segmentation and resolve any overlap using a conditional random field. Experiments on benchmark datasets demonstrate the effectiveness of the proposed approaches.
Colonic epithelial cells are a major site of macrophage inflammatory protein 3α (MIP-3α) production in normal colon and inflammatory bowel disease (2002)

These findings indicate that increased enterocyte MIP-3alpha production may play an important role in lymphocyte activation and recruitment to the colonic epithelium in Crohn's disease and ulcerative colitis.
Rapid spread of transposable p elements in experimental populations of Drosophila melanogaster. (1989)

The invasion of P elements in natural populations of Drosophila melanogaster was modeled by establishing laboratory populations with 1%, 5% and 10% P genomes and monitoring the populations for 20 generations. In one experiment, the ability of flies to either induce or suppress gonadal sterility in different generations was correlated with the amount of P element DNA. In a second experiment, the percentage of genomes that contained P elements, and the distribution of P elements among individual flies was monitored. The ability to induce gonadal dysgenesis increased rapidly each generation. However, the increase in P cytotype lagged behind by five to ten generations. The total amount of P element DNA and the frequency of flies containing P elements increased each generation. The number of P elements within individual genomes decreased initially, but then increased. Finally, the distribution of P elements within the genomes of individuals from later generations varied considerably, and this pattern differed from the parental P strain. These results suggest that the interaction between the assortment and recombination of chromosomal segments, and multiplicative transposition could result in the rapid spread of P elements in natural populations.
Kallikrein/Kinin Protects against Myocardial Apoptosis after Ischemia/Reperfusion via Akt-Glycogen Synthase Kinase-3 and Akt-Bad·14-3-3 Signaling Pathways (2004)

Our previous study has shown that human tissue kallikrein protected against ischemia/reperfusion-induced myocardial injury. In the present study, we investigated the protective role of local kallikrein gene delivery in ischemia/reperfusion-induced cardiomyocyte apoptosis and its signaling mechanisms in promoting cardiomyocyte survival. Adenovirus carrying the human tissue kallikrein gene was delivered locally into the heart using a catheter-based technique. Expression and localization of recombinant human kallikrein in rat myocardium after gene transfer were determined immunohistochemically. Kallikrein gene delivery markedly reduced reperfusion-induced cardiomyocyte apoptosis identified by both in situ nick end-labeling and DNA fragmentation. Delivery of the kallikrein gene increased phosphorylation of Src, Akt, glycogen synthase kinase (GSK)-3beta, and Bad(Ser-136) but reduced caspase-3 activation in rat myocardium after reperfusion. The protective effect of kallikrein on apoptosis and its signaling mediators was blocked by icatibant and dominant-negative Akt, indicating a kinin B2 receptor-Akt-mediated event. Similarly, kinin or transduction of kallikrein in cultured cardiomyocytes promoted cell viability and attenuated apoptosis induced by hypoxia/reoxygenation. The effect of kallikrein on cardiomyocyte survival was blocked by dominant-negative Akt and a constitutively active mutant of GSK-3beta, but it was facilitated by constitutively active Akt, catalytically inactive GSK-3beta, lithium, and caspase-3 inhibitor. Moreover, kallikrein promoted Bad.14-3-3 complex formation and inhibited Akt-GSK-3beta-dependent activation of caspase-3, whereas caspase-3 administration caused reduction of the Bad.14-3-3 complex, indicating an interaction between Akt-GSK-caspase-3 and Akt-Bad.14-3-3 signaling pathways. In conclusion, kallikrein/kinin protects against cardiomyocyte apoptosis in vivo and in vitro via Akt-Bad.14-3-3 and Akt-GSK-3beta-caspase-3 signaling pathways.
Influence of Dopants on the Suspension Properties and Reactive Electrophoretic Deposition (REPD) (2006)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Estimación de la prevalencia e incidencia mundial de la infección por virus del herpes simple de tipo 2 (2008)

OBJECTIVE: To estimate the global prevalence and incidence of herpes simplex virus type 2 (HSV-2) infection in 2003. METHODS: A systematic review was undertaken of published seroprevalence surveys describing the prevalence or incidence of HSV-2 by age and gender. For each of 12 regions, pooled prevalence values by age and gender were generated in a random-effect model. HSV-2 incidence was then estimated from these pooled values using a constant-incidence model. Values of the HSV-2 seroprevalence from the model fits were applied to the total population to estimate the numbers of people infected. FINDINGS: The total number of people aged 15-49 years who were living with HSV-2 infection worldwide in 2003 is estimated to be 536 million, while the total number of people who were newly infected with HSV-2 in 2003 is estimated to be 23.6 million. While the estimates are limited by poor availability of data, general trends are evident. For example, more women than men were infected, and the number infected increased with age. Although prevalence varied substantially by region, predicted prevalence was mostly higher in developing regions than developed regions. CONCLUSION: The prevalence of HSV-2 is relatively easy to measure since infection is lifelong and has a specific serological test. The burden of disease is less easy to quantify. Despite the often sparse data on which these estimates are based, it is clear that HSV-2 infection is widespread. The dramatic differences in prevalence between regions are worthy of further exploration.