gebhart/patrepeval huggingface dataset:
The structure and evolution of a 461 amino acid human protein C precursor and its messenger RNA, based upon the DNA sequence of cloned human liver cDNAs (1985)

Human liver cDNA coding for protein C has been synthesized, cloned and sequenced. The abundance of protein C message is approximately 0.02% of total mRNA. Three overlapping clones contain 1,798 nucleotides of contiguous sequence, which approximates the size of the protein's mRNA, based upon Northern hybridization. The cDNA sequence consists of 73 5'-noncoding bases, coding sequence for a 461 amino acid nascent polypeptide precursor, a TAA termination codon, 296 3'-noncoding bases, and a 38 base polyadenylation segment. The nascent protein consists of a 33 amino acid "signal", a 9 amino acid propeptide, a 155 amino acid "light" chain, a Lys-Arg connecting dipeptide, and a 262 amino acid "heavy" chain. Human protein C and Factor IX and X precursors possess about one third identical amino acids (59% in the gamma-carboxyglutamate domain), including two forty-six amino acid segments homologous to epidermal growth factor. Human protein C also has similar homology with prothrombin in the "leader", gamma-carboxyglutamate and serine protease domains, but lacks the two "kringle" domains found in prothrombin.
H3N2 Influenza Virus Infection Induces Broadly Reactive Hemagglutinin Stalk Antibodies in Humans and Mice (2013)

Broadly neutralizing antibodies directed against the conserved stalk domain of the viral hemagglutinin have attracted increasing attention in recent years. However, only a limited number of stalk antibodies directed against group 2 influenza hemagglutinins have been isolated so far. Also, little is known about the general level of induction of these antibodies by influenza virus vaccination or infection. To characterize the anti-stalk humoral response in the mouse model as well as in humans, chimeric hemagglutinin constructs previously developed in our group were employed in serological assays. Whereas influenza virus infection induced high titers of stalk-reactive antibodies, immunization with inactivated influenza virus vaccines failed to do so in the mouse model. Analysis of serum samples collected from human individuals who were infected by influenza viruses also revealed the induction of stalk-reactive antibodies. Finally, we show that the hemagglutinin stalk-directed antibodies induced in mice and humans have broad reactivity and neutralizing activity in vitro and in vivo. The results of the study point toward the existence of highly conserved epitopes in the stalk domains of group 2 hemagglutinins, which can be targeted for the development of a universal influenza virus vaccine in humans.
Soluble, prolonged-acting insulin derivatives. I. Degree of protraction and crystallizability of insulins substituted in the termini of the B-chain (1987)

Hydrophilic insulins, more positively charged than human insulin at neutral pH, have been prepared by substitution with basic amino acids at the termini of the B-chain and by blocking the C-terminal carboxyl group of the B-chain. The isoelectric pH of the insulin is thereby moved from 5.4 towards physiological levels. Slightly acid solutions of derivatives, in which charge has been added in the C-terminus of the B-chain, have a prolonged action in vivo, in particular if the carboxyl group is blocked. It is found that the prolonged-acting hydrophilic insulins crystallize instantly when the pH is adjusted to 7. The prolonged action is ascribed to this readiness to crystallization combined with a low solubility, which may be further decreased by increased concentration of zinc ions. Hydrophobic insulins have a prolonged action independent of the site of substitution even if the derivative is soluble at physiological pH. Some derivatives were prepared from porcine insulin by tryptic transpeptidation. N-terminal B-chain substituted insulins were prepared by alkylation of a biosynthetic single-chain insulin precursor, followed by tryptic transpeptidation rendering the double chain insulin derivative. The observed blood glucose lowering in the rabbits implies that neither N- nor C-terminal B-chain substitution results in substantial deterioration of biological potency. An index for the degree of protraction based on the blood glucose data is used to compare the insulins.
Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells (2007)

Invasion and metastasis of aggressive breast cancer cells is the final and fatal step during cancer progression, and is the least understood genetically. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Clearly, effective and nontoxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. Using a mouse model, we previously determined that metastatic breast cancer cells became significantly less invasive in vitro and less metastatic in vivo when Id-1 was down-regulated by stable transduction with antisense Id-1. It is not possible at this point, however, to use antisense technology to reduce Id-1 expression in patients with metastatic breast cancer. Here, we report that cannabidiol (CBD), a cannabinoid with a low-toxicity profile, could down-regulate Id-1 expression in aggressive human breast cancer cells. The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion. These effects seemed to occur as the result of an inhibition of the Id-1 gene at the promoter level. Importantly, CBD did not inhibit invasiveness in cells that ectopically expressed Id-1. In conclusion, CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness.
원보 : 폐렴구균 Type 23 협막다당류 생산의 최적화 (1999)

Streptococcus pneumoniae (pneumococcus) is the most frequent causative agent of acute bacterial pneumonia. Outstanding characteristic of pneumococcus is an ample polysaccharide capsule that is highly antigenic agent and is the major factor for classification of pneumococcus into more than 94 serotypes. In this study, production of capsular polysaccharide from Streptococcus pneumoniae type 23 was optimized by supplementation of metal ions or by modulation of culture conditions. When brain heart infusion (BHI) broth was supplemented with 1 mM concentration of CaCl₂, CuS0₄ and MgS0₄, growth of pneumococcus as well as polysaccharide yield were stimulated. Also slight aeration gave rise to better polysaccharide yield.
Robust Cell Line Development Using Meganucleases (2008)

Cell line development for protein production or for the screening of drug targets requires the reproducible and stable expression of transgenes. Such cell lines can be engineered with meganucleases, sequence-specific endonucleases that recognize large DNA target sites. These proteins are powerful tools for genome engineering because they can increase homologous gene targeting by several orders of magnitude in the vicinity of their cleavage site. Here, we describe in details the use of meganucleases for gene targeting in Chinese hamster ovary-K1 cells, with a special emphasis on a gene insertion procedure using a promoter-less marker gene for selection. We have also monitored the expression of genes inserted by meganucleases-induced recombination, and show that expression is reproducible among different targeted clones, and stable over a 4 mo period. These experiments were conducted with the natural yeast I-SceI meganuclease, but the general design and process can also be applied to engineered meganucleases.
Bidirectional Forwarding Detection (BFD) (2010)

This document describes a protocol intended to detect faults in the bidirectional path between two forwarding engines, including interfaces, data link(s), and to the extent possible the forwarding engines themselves, with potentially very low latency.It operates independently of media, data protocols, and routing protocols.
Validation of the interleukin-10 knockout mouse model of colitis: antitumour necrosis factor-antibodies suppress the progression of colitis (2003)

SUMMARY Advances in understanding pathogenesis and developing new therapies are hastened by the use of effective animal models of disease. In inflammatory bowel disease, such as Crohn's disease, a variety of models have been used, including the IL-10 knockout mouse. However, in order to be truly valuable, the models need to respond to existing therapy in a way which resembles the human disease. In the light of recent developments, in which refractory Crohn's disease responds well to anti-TNF antibody therapy, we set out to validate the IL-10 knockout model of Crohn's disease by examining its response to anti-TNF therapy. We developed a new scoring system for IL-10 knockout mice, similar to the Crohn's Disease Activity Index in humans, analysed stool samples for cytokines and compared the findings with histology. We found that anti-TNF antibody therapy starting at 4 weeks markedly ameliorated the disease, as judged by the clinical score or by histological analysis of the gut. Furthermore, analysis of stool samples for cytokines revealed a marked diminution of inflammatory cytokines, adding a further accurate measure of the improvement. This model may thus be useful for evaluating other therapeutic modalities of relevance to Crohn's disease.
Monoclonal antibodies that recognize lacto-N-fucopentaose III (CD15) react with the adhesion-promoting glycoprotein family (LFA-1/HMac-1/gp 150,95) and CR1 on human neutrophils. (1987)

A variety of monoclonal antibodies has been used to study the roles of surface proteins in neutrophil function. Many monoclonal antibodies that bind to human neutrophils react with the oligosaccharide lacto-N-fucopentaose III. Sequential immunoprecipitation of radiolabeled proteins from extracts of neutrophils labeled at the cell surface with 125I, and partial proteolysis peptide mapping studies were used to compare the proteins recognized by several widely used monoclonal antibodies that react with human neutrophils. The monoclonal antibodies that react with lacto-N-fucopentaose III (CD15) immunoprecipitated five distinct neutrophil surface proteins. The data indicate that CD15 monoclonal antibodies react with a subset of the LFA-1/HMac-1/gp 150,95 glycoprotein family as well as with CR1 on human neutrophils. The CD15 antibodies studied differed in their avidities for these proteins. The molecules immunoprecipitated by the CD15 antibodies tested were more resistant to proteolysis than the homologous proteins immunoprecipitated by the other monoclonal antibodies studied that react directly with the alpha M (CD11) or beta (CD18) chains of the LFA-1/HMac-1/gp 150,95 glycoprotein family. Some of the differences in antibody reactivity and protease sensitivity of the membrane proteins recognized by these antibodies may be due to differences in glycosylation. The data suggest that the antibodies studied can detect differences in post-translational modification among copies of certain surface proteins.
Theoretical and practical considerations in the application of killed poliovirus vaccine for the control of paralytic poliomyelitis. (1981)

This paper contains a summary of the principles upon which the preparation and use of killed poliovirus vaccine (KPV) are based, as well as a summary of earlier and more recent work suggesting the feasibility of formulating a KPV preparation that would be fully and durably effective in a one- or two-dose regimen. The essential factor in the preparation of such a vaccine is the inclusion of a sufficient mass of the immunizing antigen, for each of the three antigenic types of poliovirus, to induce the formation of humoral antibody and/or immunologic memory after the first dose. The results of a series of studies carried out in West African and Scandinavian countries are summarized, which suggest that such a vaccine should contain 40, 8, and 32 D-antigen units for types I, II and III, respectively. If the D-antigen unit measurement is to be used as a guide to KPV standardization, the details of the method of manufacture are important; in this regard, the method of vaccine preparation used at the Rijks Instituut voor de Volksgezondheid should serve as a reference standard for the preparation of vaccines expected to produce the effects described.
Microembolization in pigs: effects on coronary blood flow and myocardial ischemic tolerance (1999)

Coronary microembolization has been reported to increase coronary blood flow (CBF) through adenosine release. Because adenosine may increase ischemic tolerance against infarction, we tested the hypothesis that myocardial microembolization, a common finding in patients with ischemic heart disease, induces cardioprotection. Additionally, because the use of microspheres is a common tool to measure tissue perfusion, the effects of small amounts of microspheres on CBF were examined. Using anesthetized pigs, we measured CBF with a transit time flow probe on the left anterior descending coronary artery (LAD). In six pigs the relationship between the amount of injected microspheres (0-40 x 10(6), 15 micrometer in diameter, left atrial injections) and the effect on CBF was examined. Coronary hyperemia occurred, which was linearly related to the amount of microspheres injected: maximal increase in CBF (%) = 2.8 +/- 1.5 (SE) + (5.8 +/- 0.7 x 10(-7) x number of injected microspheres). Because injection of 40 x 10(6) microspheres induced a long-lasting hyperemic response, which could be blocked by 8-p-sulfophenyl theophylline, ischemic tolerance was examined in five other pigs after two injections, each of 40 x 10(6) microspheres, at a 30-min interval. Six control pigs had no injections. Ischemic tolerance was evaluated by measuring infarct size (tetrazolium stain) as the percentage of area at risk (fluorescent particles) after 45 min of LAD occlusion followed by 2 h of reperfusion. Pretreatment by microspheres increased infarct size from 60 +/- 3% of area at risk in control animals to 84 +/- 6% (P < 0.05). The injection of microspheres induced a significant hyperemic flow response without causing necrosis by itself. We conclude that microembolization, evoking coronary hyperemia, does not improve but reduces myocardial ischemic tolerance against infarction in pigs.
Systemic absorption of oral vancomycin in patients with Clostridium difficile infection (2011)

Oral vancomycin is utilized in the treatment of severe Clostridium difficile infection (CDI). We prospectively measured serum vancomycin concentrations (SVC) in patients treated with oral vancomycin. The SVC was measured by immunoassay prior to, and at least 3 days after, the administration of oral vancomycin 125 mg every 6 h. Patients treated with intravenous vancomycin were excluded. Fifty-seven patients with a mean age of 74 y (± 18) were enrolled. There was no detectable SVC in 56 patients (98%); 1 patient had a transient SVC of 6.7 μg/ml that was not detectable on subsequent testing. The severity of the CDI and/or renal failure did not have an effect on SVC. Orally administered vancomycin at 125 mg 4 times daily was not absorbed from the gastrointestinal tract.
Binding and Cytotoxicity of Conjugated and Recombinant Fusion Proteins Targeted to the Gonadotropin-Releasing Hormone Receptor (2004)

Pokeweed antiviral protein (PAP) is a plant-derived, highly potent ribosome inactivating protein that causes inhibition of protein translation and rapid cell death. We and others have delivered this protein to various cell types, including cancer cells, using hormones to specifically target cells bearing the hormone receptor. Here, we compare binding and cytotoxicity of GnRH-PAP hormonotoxins prepared either by protein conjugation (GnRH-PAP conjugate) or through recombinant DNA technology (GnRH-PAP fusion). Although GnRH-PAP conjugate protein bound specifically to and caused cell death in cells bearing the gonadotropin-releasing hormone (GnRH) receptor, we could not detect binding or cytotoxicity using two different versions of the fusion protein in receptor-positive cells. We conclude that generation of an active GnRH-PAP fusion protein may not be feasible either because both ends of the GnRH molecule are required for receptor binding, but only the NH(2) terminus is free in the fusion protein and/or that more potent analogues of GnRH (inclusion of which is not feasible in the fusion protein) are needed for efficient targeting. In contrast, the GnRH-PAP conjugate shows promise as a novel anticancer agent, capable of targeting cancer cells expressing the GnRH receptor such as prostate, breast, ovarian, endometrial, and pancreatic cells. It may also be useful as a therapeutic agent to eliminate pituitary gonadotrophs, eliminating the need for chronic GnRH analogue administration to treat hormone-sensitive diseases.
Genetic Deletion of Chemokine Receptor Ccr6 Decreases Atherogenesis inApoE-Deficient Mice (2011)

Ccr6 promotes atherosclerosis in ApoE-deficient mice, which may be due in part to Ccr6 support of normal monocyte levels in blood, as well as direct Ccr6-dependent monocyte migration.
The Spectrum of Perianal Crohn’s Disease in a Population-Based Cohort (2012)

This study provides the first detailed classification of perianal Crohn's disease in a population-based cohort.
Fully microwave-tunable universal gates in superconducting qubits with linear couplings and fixed transition frequencies (2010)

A register of quantum bits with fixed transition frequencies and weakly coupled to one another through simple linear circuit elements is an experimentally minimal architecture for a small-scale superconducting quantum information processor. Presently, the known schemes for implementing two-qubit gates in this system require microwave signals having amplitudes and frequencies precisely tuned to meet a resonance condition, leaving only the signal phases as free experimentally adjustable parameters. Here, we report a minimal and robust microwave scheme to generate fast, tunable universal two-qubit gates: simply irradiate one qubit (the ``control'') at the transition frequency of another (the ``target''). The effective coupling between them is then switched on by tuning only the frequency of this single drive tone; the drive amplitude adjusts the effective coupling strength; and the drive phase selects the particular two-qubit gate implemented. This cross-resonance effect turns on linearly with the ratio of the drive amplitude $\ensuremath{\Omega}$ to the qubit-qubit detuning $\ensuremath{\Delta}$, as compared with earlier proposals that turn on as ${(\ensuremath{\Omega}/\ensuremath{\Delta})}^{4}$.
Multipotent Adult Progenitor Cells from Swine Bone Marrow (2006)

We show that multipotent adult progenitor cells (MAPCs) can be derived from both postnatal and fetal swine bone marrow (BM). Although swine MAPC (swMAPC) cultures are initially mixed, cultures are phenotypically homogenous by 50 population doublings (PDs) and can be maintained as such for more than 100 PDs. swMAPCs are negative for CD44, CD45, and major histocompatibility complex (MHC) classes I and II; express octamer binding transcription factor 3a (Oct3a) mRNA and protein at levels close to those seen in human ESCs (hESCs); and have telomerase activity preventing telomere shortening even after 100 PDs. Using quantitative-reverse transcription-polymerase chain reaction (Q-RT-PCR), immunofluorescence, and functional assays, we demonstrate that swMAPCs differentiate into chondrocytes, adipocytes, osteoblasts, smooth muscle cells, endothelium, hepatocyte-like cells, and neuron-like cells. Consistent with what we have shown for human and rodent MAPCs, Q-RT-PCR demonstrated a significant upregulation of transcription factors and other lineage-specific transcripts in a time-dependent fashion similar to development. When swMAPCs were passaged for 3-6 passages at high density (2,000-8,000 cells per cm(2)), Oct3a mRNA levels were no longer detectable, cells acquired the phenotype of mesenchymal stem cells (CD44(+), MHC class I(+)), and could differentiate into typical mesenchymal lineages (adipocytes, osteoblasts, and chondroblasts), but not endothelium, hepatocyte-like cells, or neuron-like cells. Even if cultures were subsequently replated at low density (approximately 100-500 cells per cm(2)) for >20 PDs, Oct3a was not re-expressed, nor were cells capable of differentiating to cells other than mesenchymal-type cells. This suggests that the phenotype and functional characteristics of swMAPCs may not be an in vitro culture phenomenon.
Scalar operand networks: on-chip interconnect for ILP in partitioned architectures (2003)

The bypass paths and multiported register files in microprocessors serve as an implicit interconnect to communicate operand values among pipeline stages and multiple ALU. Previous superscalar designs implemented this interconnect using centralized structures that do not scale with increasing ILP demands. In search of scalability, recent microprocessor designs in industry and academia exhibit a trend towards distributed resources such as partitioned register files, banked caches, multiple independent compute pipelines, and even multiple program counters. Some of these partitioned microprocessor designs have begun to implement bypassing and operand transport using point-to-point interconnects rather than centralized networks. We call interconnects optimized for scalar data transport, whether centralized or distributed, scalar operand networks. Although these networks share many of the challenges of multiprocessor networks such as scalability and deadlock avoidance, they have many unique requirements, including ultra-low latencies (a few cycles versus tens of cycles) and ultra-fast operation-operand matching. This paper discusses the unique properties of scalar operand networks, examines alternative ways of implementing them, and describes in detail the implementation of one such network in the Raw microprocessor. The paper analyzes the performance of these networks for ILP workloads and the sensitivity of overall ILP performance to network properties.
Sequence of a Complementary DNA from Cucumis sativus L. Encoding the Stearoyl-Acyl-Carrier Protein Desaturase (1991)

The stearoyl-ACP2 desaturase (EC 1.14.99.6) is responsible for introducing a cis double bond between carbons 9 and 10 ofstearoyl-ACP to form oleoyl-ACP (1) (Table I).Purification of the avocado enzyme and isolation of cDNA clones from Ricinus communis (castor) and Cucumis sativus L. (cucumber) and their corresponding amino acid sequences have recently been reported (2).Here we present the nucleotide sequence of a full-length cucumber cDNA (from plasmid pCSDl) and the deduced amino acid sequence of the open reading frame.The 396 amino acid open reading frames of the cucumber and the castor clones are 80.1% identical at the nucleotide level and 88. 1% identical at the amino acid level.ACKNOWLEDGMENT We thank Dr. J. Greenler and Dr. W. Becker for the generous gift of a