gebhart/patrepeval huggingface dataset:
Functional Antagonism between Endogenous Mouse Growth Hormone (GH) and a GH Analog Results in Dwarf Transgenic Mice* (1991)

A dwarf transgenic mouse (DTM) line has been established in which mice express relatively high levels of a mutated bovine (b) GH gene. This bGH analog binds to mouse liver membrane preparations with an affinity similar to that of wild-type bGH. The mean growth ratio of these mice is approximately 0.7 relative to that of their nontransgenic littermates. Serum insulin-like growth factor-I (IGF-I) levels of DTM were found to be approximately half those in nontransgenic littermates. Liver GH receptor levels were up-regulated in DTM or wild-type bGH transgenic mice. Pituitary GH levels were negatively correlated with serum IGF-I concentrations. Wild-type bGH transgenic mice contain relatively high serum IGF-I and low pituitary GH levels, whereas DTM possess low serum IGF-I and high pituitary GH levels. The decrease in serum IGF-I resulting from the interaction between the bGH analog, the endogenous mouse GH, and GH receptor(s) apparently leads to a dwarf phenotype. These data suggest that this bGH analog has uncoupled GH ligand-receptor binding from IGF-I production and acts as a functional antagonist to the action of endogenous mGH.
Mutation in NS2, a nonstructural protein of influenza A virus, extragenically causes aberrant replication and expression of the PA gene and leads to generation of defective interfering particles. (1990)

Several consecutive undiluted passages of infectious virus are usually required to obtain defective interfering particles of influenza virus. In contrast, a reassortant (Wa-182) of influenza A/WSN, which we isolated, whose NS gene was replaced with the NS gene of A/Aichi, was readily converted to defective interfering form after only a single high-multiplicity infection. The defective interfering particles of Wa-182 were devoid of the PA gene (RNA segment 3) but possessed several species of subgenomic RNAs of the PA gene origin. Such aberrant replication of the PA gene was shown to be caused by an extragenic effect of the NS gene of Wa-182, because, when the NS gene of Wa-182 was singly transferred to the wild-type A/Ann Arbor/6/60 virus, the recipient showed exactly the same features. Analysis of nucleotide sequence demonstrated that the NS gene of Wa-182 contained three point mutations relative to the wild-type NS gene that resulted in two amino acid substitutions in the nonstructural protein NS2, suggesting that the mutation in NS2 protein affected the normal replication of the PA gene of Wa-182. The results also suggest that the NS2 protein plays an important role in the synthesis of intact genome RNAs.
Capillary droplets on Leidenfrost micro-ratchets (2012)

Leidenfrost ratchets are structures with the ability of transporting liquid droplets when heated over the critical Leidenfrost temperature. Once this temperature is reached, the droplet levitates over the surface and moves in the direction marked by the slope of the ratchet at terminal velocities around 10 cm/s. Here we provide new experiments with micron-sized ratchets, which have been produced with picosecond pulse laser ablation. In the following work, we use a simple method to measure the thrust driving droplets of capillary size over the micro-ratchets. The mechanism responsible for the force acting on the drop on superheated ratchets has been recently under debate. We extend the recently proposed “viscous mechanism” proposed by Dupeux et al. [Europhys. Lett. 96, 58001 (2011)10.1209/0295-5075/96/58001] to capillary droplets and find good agreement with our measurements.
Bacillus subtilis CodY represses early-stationary-phase genes by sensing GTP levels (2001)

CodY, a highly conserved protein in the low G + C, gram-positive bacteria, regulates the expression of many Bacillus subtilis genes that are induced as cells make the transition from rapid exponential growth to stationary phase and sporulation. This transition has been associated with a transient drop in the intracellular pool of GTP. Many stationary-phase genes are also induced during exponential-growth phase by treatment of cells with decoyinine, a GMP synthetase inhibitor. The effect of decoyinine on an early-stationary-phase gene is shown here to be mediated through CodY and to reflect a reduction in guanine nucleotide accumulation. CodY proved to bind GTP in vitro. Moreover, CodY-mediated repression of target promoters was dependent on a high concentration of GTP, comparable to that found in rapidly growing exponential-phase cells. Because a codY-null mutant was able to sporulate under conditions of nutrient excess, CodY also appears to be a critical factor that normally prevents sporulation under such conditions. Thus, B. subtilis CodY is a novel GTP-binding protein that senses the intracellular GTP concentration as an indicator of nutritional conditions and regulates the transcription of early-stationary-phase and sporulation genes, allowing the cell to adapt to nutrient limitation.
Treatment of chemotherapy-induced neutropenia by subcutaneously administered granulocyte colony-stimulating factor with optimization of dose and duration of therapy. (1989)

In patients who have not received extensive prior chemotherapy or radiotherapy, it has been previously demonstrated that granulocyte colony-stimulating factor (G-CSF) abrogated the leukopenia following administration of melphalan (25 mg/m2). This study examined the necessity of a prechemotherapy period of G-CSF administration and the effect of varying the timing and duration of postchemotherapy G-CSF. Initially, patients received 0.3, 1.0, 3.0, and 10 micrograms/kg/d subcutaneously on days 1 to 5 and days 10 to 18. Melphalan was given on day 9. In the next portion of the study melphalan was administered on day 1 and G-CSF, 10 micrograms/kg/d, was administered by subcutaneous infusion on five schedules: (1) days 2 to 13; (2) days 8 to 13; (3) days 2 to 18; (4) days 8 to 18; (5) days -9 to -2 and 2 to 13. G-CSF produced a rapid and sustained elevation in neutrophil levels within 24 hours even when started 8 days after melphalan. This treatment was sufficient to abrogate the neutropenia in patients who had received no prior chemotherapy. It was not necessary to continue G-CSF for more than 7 days. G-CSF did not consistently alter the course of the thrombocytopenia that followed this dose of melphalan. G-CSF was well tolerated, although mild bone pain occurred and was reduced with acetaminophen. One of 22 patients developed cellulitis at an infusion site. We conclude that after melphalan chemotherapy, G-CSF may need to be given for only a short period to prevent chemotherapy-induced neutropenia, and that G-CSF induces a rapid rise in neutrophil levels even when started 8 days after melphalan administration.
Natalizumab plus Interferon Beta-1a for Relapsing Multiple Sclerosis (2006)

Natalizumab added to interferon beta-1a was significantly more effective than interferon beta-1a alone in patients with relapsing multiple sclerosis. Additional research is needed to elucidate the benefits and risks of this combination treatment. (ClinicalTrials.gov number, NCT00030966.).
Identification of putative downstream genes of Oct‐3, a pluripotent cell‐specific transcription factor (1996)

A large proportion of pluripotent cell-specific genes appear to be downstream targets of Oct-3.
Comparative Effects of Microtubules Disruption on Glucocorticoid Receptor Functions in Proliferating and Quiescent Cells (2010)

We have recently demonstrated that the alkaloid colchicine (COL) inhibits glucocorticoid receptor (GR) transcriptional activity. In addition, we described proteasome-mediated degradation of GR in COL-treated HeLa cells. While these effects were previously attributed to cell cycle arrest in G2/M phase, this explanation is not applicable for nonproliferating cells such as human hepatocytes (HH). In the current study, we compared COL-mediated microtubule disruption and cell cycle arrest with selected GR functions in HeLa cells and HH as models of proliferating and quiescent cells, respectively. Microtubule disruption led to irreversible decrease in GR binding capacity and protein level in HeLa cells. None of the parameters was restored 24 hours after COL withdrawal. In contrast, dexamethasone (DEX) binding was increased in HH at the beginning of the treatment, with following transient activation of extracellular signal-regulated kinase (ERK). The findings of these investigations emphasize the GR-signaling differences between primary and transformed cells.
Cytomegalovirus detection in cryopreserved semen samples collected for therapeutic donor insemination (1997)

The presence of cytomegalovirus (CMV) in semen was retrospectively evaluated in 178 cryopreserved semen samples obtained from 97 donors recruited by two sperm banks. Thirty-three (34.0%) donors were CMV-seronegative, 51 (52.6%) were CMV-seropositive and 13 (13.4%) had an unknown serological status. CMV was detected in sperm specimens by cell culture and polymerase chain reaction (PCR). CMV was detected in five (2.8%) samples from two (2.0%) donors by cell culture and in 10 samples (5.6%) from five donors (5.1%) by PCR; all the samples which were positive by cell culture were also positive by PCR. Our data indicate that cryopreserved semen specimens obtained from healthy volunteer donors represent a potential source of CMV infection through therapeutic donor insemination. PCR, which is more sensitive than cell culture, should be used for direct and rapid identification of CMV in semen samples collected from volunteer donors. CMV detection in semen by PCR could be advantageously compared to CMV-antibody tests in serum which are only indicative of a former CMV infection.
An antigen immunologically related to the external domain of gp185 is shed from nude mouse tumors overexpressing the c-erbB-2 (HER-2/neu) oncogene. (1991)

An antigen, immunologically related to the external domain of the c-erbB-2 (HER-2/neu) protein, was found shed into the serum of nude mice bearing tumors that overexpress the c-erbB-2 protein (gp185). Utilizing paired combinations from a panel of monoclonal antibodies (TAbs 250-265), with specificity for extracellular epitopes of gp185, an immunoradiometric assay was developed to quantitate this shed antigen. The immunoradiometric assay detected membrane-bound and soluble gp185 as well as a soluble derivative corresponding in sequence to the extracellular domain of gp185 (designated gp75). This recombinantly expressed gp75 was immunoaffinity purified and used to generate a standard curve from which serum samples were quantitated. Increases in antigen levels measured in the sera of tumor-bearing nude mice correlated with both overexpression of the c-erbB-2 protein and increased tumor volume. Positive sera were obtained from mice given implants of NIH3T3 cells transfected with c-erbB-2 complementary DNA (NIH3T3t), or ovarian (SK-OV-3) or breast (MDA-MB-361) tumor cell lines overexpressing the c-erbB-2 protein. In mice bearing NIH3T3t tumors, increases in tumor volume from 80 to 9000 mm3 resulted in levels of shed antigen from 8 to greater than 1000 ng/ml gp75 equivalents. Sera from mice with c-erbB-2-negative tumors or tumors overexpressing the epidermal growth factor receptor were negative in the assay. This assay, and the quantitation of shed antigen levels, may have diagnostic or monitoring utility in cancers, such as breast and ovarian, in which the c-erbB-2 protein is overexpressed.
Interleukin-18 binding protein reduces b16 melanoma hepatic metastasis by neutralizing adhesiveness and growth factors of sinusoidal endothelium. (2003)

We studied the role of endogenous interleukin (IL)-18 in hepatic metastasis by blocking this cytokine using the naturally occurring IL-18 binding protein (IL-18BP). A single i.p. dose of IL-18BP given 30 min before intrasplenic injection of murine B16 melanoma (B16M) cells reduced the number of hepatic metastatic foci by 75% and metastatic volume by 80%. Same treatment reduced the intrahepatic retention of luciferase-transfected B16M by 50% and abolished VCAM-1 up-regulation in the hepatic microvasculature, as assessed by reverse transcription-PCR, Western blot, and immunohistochemistry. Twelve hours after IL-18BP, hepatic sinusoidal endothelium (HSE) cells were isolated, and adhesion of B16M cells to these cultured HSE cells was reduced to the level of vehicle-treated mice. IL-18BP treatment of mice with established micrometastases resulted in a 25% decrease in metastasis number and 40% decrease in metastasis volume, suggesting inhibition of endogenous growth factors. Indeed, the addition of IL-18BP to normal HSE abolished the release of melanoma cell growth factor(s) induced by B16M. IL-18 promoted the in vitro growth of B16M and human melanoma cells, which was IL-1 dependent. These data demonstrate a significant role of endogenous IL-18 on hepatic metastasis by up-regulating melanoma cell adhesion to HSE cells and tumor growth, implicating a possible antimetastatic benefit of neutralizing IL-18.
RECOMENDACIONES PARA EL USO DE UN MODELO DE SOPORTE DE SOFTWARE Informática (2006)

This work is focused in the analysis of the software support state of art. The themes in this paper can help to the application of a model to carry out the software supports activities by investigation groups in universities.The application of this proposal aims to put the customers in the developer group attention. The author has described the creation, organization, structure and roles involved in the constitution of software supports teams. Finally, it is included a set of recommendations to put in practice the theoretical proposal in organizations.
Word sense disambiguation (2009)

Word sense disambiguation (WSD) is the ability to identify the meaning of words in context in a computational manner. WSD is considered an AI-complete problem, that is, a task whose solution is at least as hard as the most difficult problems in artificial intelligence. We introduce the reader to the motivations for solving the ambiguity of words and provide a description of the task. We overview supervised, unsupervised, and knowledge-based approaches. The assessment of WSD systems is discussed in the context of the Senseval/Semeval campaigns, aiming at the objective evaluation of systems participating in several different disambiguation tasks. Finally, applications, open problems, and future directions are discussed.
Complexity, Democratisation and Conflict (2008)

This chapter builds upon the combination of complexity theory and post-structuralism to draw out the implications of complexity for understanding political conflicts. By examining the dynamics of conflict in sites such as Northern Ireland and the Middle East, the argument points to a range of issues that give rise to multiple readings of conflict situations. On this basis, it is important to realise that attempts to reduce conflicts to their simplest components do not necessarily facilitate understanding of the contemporary dynamics of a contested situation. Explanations of different disputes as primarily national, territorial, religious, ethnic, or cultural can help to obscure the interaction of a multiplicity of reasons for a particular conflict. However, rather than merely fusing together some of these explanatory arguments to provide a more comprehensive model, this chapter suggests that varying issues come to the fore in different political contestations.
[Study on high mobility group-1 protein in patients with multiple trauma]. (2005)

Serum HMG-1 increases in patients with trauma and is positively correlated with severity of trauma. Serial determination of HMG-1 is helpful to discover clinical infection earlier. HMG-1 can be used as a warning indicator of the onset of MODS.
Phase I study of recombinant tumor necrosis factor in cancer patients. (1987)

Tumor necrosis factor is a cytokine derived from activated macrophages. This agent is cytostatic and cytolytic against transformed human cell lines in vitro and has in vivo activity against a variety of murine tumors. We report a clinical study of the pharmacokinetics, toxicity, and biological activity of i.v. and i.m. administered recombinant human tumor necrosis factor (rTNF). Twenty patients with metastatic cancer were given rTNF in doses ranging from 1 to 200 micrograms/m2 by alternating i.m. and i.v. bolus injections with a minimal intervening period of 72 h. Each patient received a maximum of eight treatments given twice weekly over a 4-week period. With i.v. bolus administration, serum concentrations of rTNF were detected by enzyme-linked immunosorbent assay at doses of 25 micrograms/m2 or greater. The clearance of rTNF in the serum was described by a monoexponential equation with a half-life calculated to be 14-18 min. After i.m. administration, serum concentrations of rTNF were consistently detected by enzyme-linked immunosorbent assay at doses of 150 micrograms/m2 or greater. Peak concentrations were observed within 2 h and rTNF was occasionally detected, at the lower limit of sensitivity of the assay, at 24 h postinjection. rTNF was well tolerated clinically in this dose range, and there was evidence of antitumor effect.
Visualization of Retroviral Replication in Living Cells Reveals Budding into Multivesicular Bodies (2003)

Retroviral assembly and budding is driven by the Gag polyprotein and requires the host-derived vacuolar protein sorting (vps) machinery. With the exception of human immunodeficiency virus (HIV)-infected macrophages, current models predict that the vps machinery is recruited by Gag to viral budding sites at the cell surface. However, here we demonstrate that HIV Gag and murine leukemia virus (MLV) Gag also drive assembly intracellularly in cell types including 293 and HeLa cells, previously believed to exclusively support budding from the plasma membrane. Using live confocal microscopy in conjunction with electron microscopy of cells generating fluorescently labeled virions or virus-like particles, we observed that these retroviruses utilize late endosomal membranes/multivesicular bodies as assembly sites, implying an endosome-based pathway for viral egress. These data suggest that retroviruses can interact with the vps sorting machinery in a more traditional sense, directly linked to the mechanism by which cellular proteins are sorted into multivesicular endosomes.
Failure of Bone Marrow Cells to Transdifferentiate into Neural Cells in Vivo (2002)

Reports have suggested that adult mouse bone marrow cells (BMCs) are capable of transdifferentiating into cells with neural characteristics in the central nervous system (CNS) ([1][1],[2][2]). Because side-population (SP) cells within whole bone marrow are hematopoietic stem cells that can
Large-Scale Prediction of Protein Structure and Function from Sequence (2006)

The identification of novel drug targets from genomic data involves the large-scale analysis of many protein sequences. Methods for automated structure and function prediction are an essential tool for this purpose. In this review we concentrate on the recent developments in the field of protein structure prediction and how these can be used to gain hints about the function of proteins. The current state-of-the-art is highlighted through recent community-wide experiments aimed at comparing different approaches. For structure prediction this allows the identification of key improvements to increase the crucial sequence to structure alignment needed for accurate models. Function prediction is a rapidly maturing field that is still being benchmarked. Definitions for protein function are presented and available methods, mostly concentrating on functional site descriptors and structural motifs, presented.
Chemical instability of protein pharmaceuticals: Mechanisms of oxidation and strategies for stabilization (1995)

Oxidation is one of the major chemical degradation pathways for protein pharmaceuticals. Methionine, cysteine, histidine, tryptophan, and tyrosine are the amino acid residues most susceptible to oxidation due to their high reactivity with various reactive oxygen species. Oxidation during protein processing and storage can be induced by contaminating oxidants, catalyzed by the presence of transition metal ions and induced by light. Oxidative modification depends on the structural features of the proteins as well as the particular oxidation mechanisms inherent in various oxidative species, and may also be influenced by pH, temperature, and buffer composition. Protein oxidation may result in loss of biological activity and other undesirable pharmaceutical consequences. Strategies to stabilize proteins against oxidation can be classified into intrinsic methods (site-directed mutagenesis and chemical modification), physical methods (solid vs. liquid formulations) and use of chemical additives. The optimum choice of chemical additives needs to be evaluated on the basis of the specific oxidation mechanism. Oxidation induced by the presence of oxidants in the system is referred to as a non-site-specific mechanism. Under such conditions, oxidation can be effectively inhibited by the appropriate addition of antioxidants or free radical scavengers. metal-catalyzed oxidation is a site-specific process, in which the addition of antioxidants may accelerate the oxidation reaction. Careful screening of chelating agents has been shown to be an alternative method for preventing metal-catalyzed oxidation. (c) 1995 John Wiley & Sons, Inc.
It’s time… (2002)

Bekes, Carolyn MD; Stechert, Judy; Rudis, Maria I. PharmD; Brilli, Richard J. MD; Rainey, Thomas G. MD Author Information
Manipulation of androgens and alterations in the androgen receptor axis in prostate cancer. (2008)

Androgens play a key role in prostate cancer (PCa) development and progression. For decades, androgen deprivation therapy (ADT) has been the primary treatment for men with metastatic prostate cancer. ADT initially results in the regression of prostate cancers, however, this effect is limited and patients inevitably develop an androgen refractory form of the disease. Many studies have implicated the androgen receptor (AR), the key mediator of androgen action, as an important player in PCa recurrence. Changes such as AR gene amplification, AR mutations, and in AR subcellular localization, and AR coregulator status that result in the upregulation of AR activity are often associated with androgen refractory prostate cancers. This review seeks to highlight some of the changes in the AR axis in androgen refractory tumors and the recent advances in ADT. A greater understanding of the AR axis will provide a basis for improving existing methods and developing new methods for the treatment of prostate cancer.
Use of Morpholinonucleosides To Conjugate Oxidized DNA Bases to Proteins (1996)

The universal method of Erlanger and Beiser was unsuccessful in conjugating 5-hydroxycytidine to proteins because of the instability of the base under the conditions used. A new strategy was developed to conjugate fragile modified nucleosides to proteins. This involves the use of morpholino derivatives of modified nucleosides. The validity of this method was demonstrated by the production of polyclonal antibodies specific for the DNA modification, 8-oxo-7,8-dihydro-2'-deoxyguanosine.