gebhart/patrepeval huggingface dataset:
Constitutive expression of a truncated INT3 gene in mouse mammary epithelium impairs differentiation and functional development. (1995)

INT3 is interrupted by retroviral DNA insertion in approximately 18% of primary Czech mouse mammary tumors induced by mouse mammary tumor virus. One consequence of these insertions is the production of a 2.4-kilobase, tumor-specific RNA transcript encoding the entire intracellular domain of the Int3 protein which is initiated from the 3' long terminal repeat promoter of the inserted viral genome. Female mice (FVB-3) transgenic for a genomic fragment comprised of this truncated region of INT3 express the 2.4-kilobase truncated INT3 transcript and exhibit focal mammary tumors at 100% penetrance. INT3 is a member of a family of genes, highly conserved through evolution and characterized by Drosophila melanogaster Notch and Caenorhabditis elegans lin-12, the function of which relates to cell fate determination. Upon transfection into the appropriate hosts, expression vectors of truncated Notch and lin-12, representing their respective cytoplasmic domains, have been demonstrated to effect their complete gene function with respect to cell fate determination. This suggests that the extracellular portion of these proteins function only to regulate activity. Reciprocal transplantation of transgenic FVB-3 and normal mammary tissue to the epithelium-divested fat pads of the respective donor females demonstrates that FVB-3 mammary epithelium is unable to grow and/or to functionally differentiate. However, normal epithelium grows and fully differentiates in transgenic FVB-3 fat pads, indicating that the dysfunction of FVB-3 mammary glands is due to a deficiency inherent in their epithelium. Electron microscopy reveals that transgenic INT3 epithelial cells do not form intercellular junctional complexes in the developing subadult mammary gland. The hormonal stimulation of pregnancy overcomes the deficiency for ductal growth so apparent in the virgin gland such that pregnant FVB-3 glands produce complete ductal systems. Nevertheless, during pregnancy, FVB-3 mammary cells fail to form secretory lobules and to produce milk. Examination of INT3 expression by immunocytochemistry and reverse transcriptase-PCR show that INT3 is expressed constitutively in mammary stroma and epithelia at all stages of postpubertal mammary evolution. These results indicate that deregulated expression of a truncated Int3 in mammary epithelial cells limits their capacity to perform the cell fate decisions required for morphogenesis and functional differentiation.
Ribosomal DNA spacer-length polymorphisms in barley: mendelian inheritance, chromosomal location, and population dynamics. (1984)

Spacer-length (sl) variation in ribosomal RNA gene clusters (rDNA) was surveyed in 502 individual barley plants, including samples from 50 accessions of cultivated barley, 25 accessions of its wild ancestor, and five generations of composite cross II (CCII), an experimental population of barley. In total, 17 rDNA sl phenotypes, made up of 15 different rDNA sl variants, were observed. The 15 rDNA sl variants comprise a complete ladder in which each variant differs in length from adjacent variants by approximately equal to 115 nucleotide pairs. Studies of four rDNA sl variants in an F2 population showed that these variants are located at two unlinked loci, Rrn1 and Rrn2, each with two codominant alleles. Using wheat-barley addition lines, we determined that Rrn1 and Rrn2 are located on chromosomes 6 and 7, respectively. The nonrandom distribution of sl variants between loci suggests that genetic exchange occurs much less frequently between than within the two loci, which demonstrates that Rrn1 and Rrn2 are useful as new genetic markers. Frequencies of rDNA sl phenotypes and variants were monitored over 54 generations in CCII. A phenotype that was originally infrequent in CCII ultimately became predominant, whereas the originally most frequent phenotype decreased drastically in frequency, and all other phenotypes originally present disappeared from the population. We conclude that the sl variants and/or associated loci are under selection in CCII.
On Active-Site Heterogeneity in Pyrolyzed Carbon-Supported Iron Porphyrin Catalysts for the Electrochemical Reduction of Oxygen:  An In Situ Mössbauer Study (2002)

Some FeTPP−Cl/carbon electrocatalysts, heat-treated at temperatures up to 800 °C, have been studied with cyclic voltammetry, x-ray photoelectron spectroscopy, extended X-ray absorption fine structure, and in situ Mössbauer spectroscopy. It appears that the heat treatment induces considerable site heterogeneity in electronic terms, although structurally the Fe−N4 moiety seems persistent. The data indicate that only part of these Fe−N4 sites contributes to the activity for the electrochemical reduction of O2 but that they operate according to the well-known redox mechanism.
Integration of Microseismic Fracture Mapping Results With Numerical Fracture Network Production Modeling in the Barnett Shale (2006)

Abstract This paper presents the results of integrating microseismic fracture mapping with numerical production modeling of fracture networks in the Barnett shale. Microseismic fracture mapping has shown that hydraulic fracture treatments create large-scale fracture networks in the Barnett shale1–2. In this paper an approach is presented, where the fracture network measured with microseismic mapping is approximated with a numerical production simulator that discretely models the network structure in both vertical and horizontal wells. The work includes a production history match of a vertical Barnett shale well, where the microseismic mapping results were directly used to approximate a fracture network in the reservoir simulator, resulting in an estimate of effective fracture network length, average fracture conductivity and effective drainage area. In addition, a parametric study for horizontal wells is presented to show how fracture network size and density, fracture conductivity, matrix permeability and gaps in the network affect well productivity. Simulations on the effect of fracture face damage along the network, the effect of non-darcy flow in the network, and tapered fracture network conductivity that decreases away from the well are also included. The numerical model was also used to simulate how a pressure buildup test would appear based on given fracture network properties, which could be a useful diagnostic to evaluate the effectiveness of the fracture network. The results of this work illustrate how different fracture network characteristics impact well performance, which is critical for improving future horizontal well completion and fracturing strategies in the Barnett shale. This could include optimizing the number of fracture stages along the lateral, length of the lateral, treatment sizes, and perforation strategies as well as enhancing fracture network conductivity and the effectiveness of re-fracture treatments. The work also shows how microseismic mapping results can be integrated with production modeling, thereby providing a tool for more realistic infill drilling and well placement studies in the Barnett shale or similar types of reservoirs.
Enhanced clearance of Aβ in brain by sustaining the plasmin proteolysis cascade (2008)

The amyloid hypothesis states that a variety of neurotoxic beta-amyloid (Abeta) species contribute to the pathogenesis of Alzheimer's disease. Accordingly, a key determinant of disease onset and progression is the appropriate balance between Abeta production and clearance. Enzymes responsible for the degradation of Abeta are not well understood, and, thus far, it has not been possible to enhance Abeta catabolism by pharmacological manipulation. We provide evidence that Abeta catabolism is increased after inhibition of plasminogen activator inhibitor-1 (PAI-1) and may constitute a viable therapeutic approach for lowering brain Abeta levels. PAI-1 inhibits the activity of tissue plasminogen activator (tPA), an enzyme that cleaves plasminogen to generate plasmin, a protease that degrades Abeta oligomers and monomers. Because tPA, plasminogen and PAI-1 are expressed in the brain, we tested the hypothesis that inhibitors of PAI-1 will enhance the proteolytic clearance of brain Abeta. Our data demonstrate that PAI-1 inhibitors augment the activity of tPA and plasmin in hippocampus, significantly lower plasma and brain Abeta levels, restore long-term potentiation deficits in hippocampal slices from transgenic Abeta-producing mice, and reverse cognitive deficits in these mice.
Design Considerations for a Message File Server (1984)

In this paper we describe a message server facility for handling large organizational archives of messages in an office information system environment. Messages can be retrieved according to attribute values specified and to some pattern of words appearing in the text of the message. We discuss design decisions and performance considerations in this environment and we derive analytic formulas for the optimal choice of the parameters of the message file organization.
Molecular basis of mild hyperphenylalaninaemia in Poland. (1997)

The major cause of the different forms of hyperphenylalaninaemia (HPA) is mutations in the gene encoding phenylalanine hydroxylase (PAH). The aim of this study was to determine the mutations responsible for mild forms of HPA and to relate different clinical phenotypes of HPA patients to their PAH genotypes. Four "mild" mutations, including the most frequent A403V and R297H mutations, occurred exclusively in mild hyperphenylalaninaemia (MHP). Mutations A104D, R243Q, R241H, and Y414C were detected in patients with mild phenylketonuria (mild PKU) only. These results may be useful in establishing a molecular differential diagnosis for PAH deficiency in Poland.
Separation of human breast cancer cells from blood by differential dielectric affinity. (1995)

Electrorotation measurements were used to demonstrate that the dielectric properties of the metastatic human breast cancer cell line MDA231 were significantly different from those of erythrocytes and T lymphocytes. These dielectric differences were exploited to separate the cancer cells from normal blood cells by appropriately balancing the hydrodynamic and dielectrophoretic forces acting on the cells within a dielectric affinity column containing a microelectrode array. The operational criteria for successful particle separation in such a column are analyzed and our findings indicate that the dielectric affinity technique may prove useful in a wide variety of cell separation and characterization applications.
The Safety Profile of Naltrexone in the Treatment of Alcoholism (1997)

This is the largest study to date describing the safety of naltrexone in a heterogeneous population of persons with alcoholism. No new safety concerns were identified.
A Dose Ranging Study of the Pharmacokinetics, Safety, and Preliminary Efficacy of Lamivudine in Children and Adolescents with Chronic Hepatitis B (2000)

ABSTRACT Fifty-three patients with chronic hepatitis B and active viral replication were studied for 4 weeks while on treatment and for 12 weeks after treatment with the oral nucleoside analogue lamivudine. Children aged 2 to 12 years were randomized to receive twice-daily doses of 0.35, 1.5, or 4 mg of lamivudine solution per kg of body weight or once-daily doses of 3 mg of lamivudine solution per kg. Adolescents aged 13 to 17 years received lamivudine at 100 mg (as tablets). Blood samples for pharmacokinetic assay were taken on days 1 and 28. Lamivudine was rapidly absorbed following oral administration, with the maximum concentration in serum being reached 0.5 to 1 h postdosing. Apparent oral clearance (CL/F) was higher in younger children and decreased with age, with CL/F values for adolescents reaching those seen for adults by the age of 12. All doses produced a dramatic fall in serum hepatitis B virus (HBV) DNA levels, with a median reduction of ≥99.5% after 4 weeks of treatment and with the levels returning to the baseline levels posttreatment. The correlation of dose, area under the concentration-time curve (AUC), and changes in HBV DNA levels, as measured by the Chiron Quantiplex assay, showed maximal antiviral effects (99.9% inhibition and a reduction of the amount of HBV DNA of approximately 3 log 10 ) at 3 mg/kg/day, with no discernible increase in effect seen whether the drug was given at 4 mg/kg twice daily or whether it was given once daily or twice daily. The limit of detection of the assay (2.5 pg/ml) was reached for some but not all patients across the dose ranges, with the smallest number ( n = 2) of those having values negative by the Chiron Quantiplex assay being in the lowest-dose group. The 13- to 17-year-olds showed a similar overall response in terms of the HBV DNA level reduction compared to that for patients younger than age 13. Analysis of the same samples by PCR, which has a lower limit of sensitivity than the Chiron Quantiplex assay, also showed average drops in HBV DNA levels of about 3 log 10 at 4 weeks for patients for which the AUC was ≥4,000 ng · h/ml, confirming the conclusions given above. Lamivudine treatment was well tolerated at all doses, with no significant adverse events or laboratory data changes. On the basis of pharmacokinetic and pharmacodynamic data, a 3-mg/kg/day dose in children (ages 2 to 12 years) with chronic hepatitis B provides levels of exposure and trough concentrations similar to those seen in adults following the receipt of doses of 100 mg. The 100-mg dose is being evaluated in a large phase III study with HBV-infected pediatric patients.
The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. (1994)

Late-phase human T-cell lymphotropic virus I-associated adult T-cell leukemia cells express IL-2 receptors (IL-2R) but no longer produce IL-2. We have reported that the IL-2-independent adult T-cell leukemia line HuT-102 secretes a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and lymphokine-activated killer cell activity. Stimulation of proliferation of the cytokine-dependent human T-cell line Kit-225 mediated by HuT-102-conditioned medium or by 3200-fold-purified IL-T was not blocked by the addition of antibodies against IL-2 or IL-2R alpha subunit. However, IL-T-mediated stimulation of this human T-cell line was inhibited by addition of Mik-beta 1, an antibody that binds specifically to IL-2R beta subunit. In addition, the activation of large granular lymphocytes to lymphokine-activated killer cells mediated by IL-T-containing conditioned medium was not blocked by antibodies directed toward IL-2 or IL-2 alpha but was inhibited by an antibody to IL-2R beta, suggesting the requirement of this receptor subunit for IL-T action. This conclusion was confirmed using an IL-3-dependent murine myeloid precursor cell line, 32D, that expresses IL-2R alpha and IL-2R gamma, but not IL-2R beta. Neither IL-2 nor IL-T stimulated 32D cell proliferation. However, after transfection with the gene encoding human IL-2R beta, 32D beta cells proliferated on addition of either cytokine. The IL-T-mediated stimulation of 32D beta proliferation was inhibited by an anti-IL-2R beta antibody but not by an anti-IL-2 antibody. Thus, the IL-T-mediated stimulation of T-cell and lymphokine-activated killer cell activation requires the expression of the IL-2R beta subunit.
Analysis of Abnormality Diagnosis in Emergency Medicine by Integrating K-means and Decision Trees-a Case Study of Dongyang People’s Hospital in China (2014)

The performance of a triage system can facilitate patient classification in an emergency department, enabling patients in critical condition to receive better medical care; therefore, more perfect allocation and use of resources of emergency medical treatment are required. The correctness of nurses and doctors is related to triage medical care quality, patient satisfaction, and life safety. Hence, how to effectively extract experience by data mining and triage in the background of continuously increasing numbers of emergency patients is an issue worth exploring. Based on the case of Dongyang People’s Hospital in China, this study established a triage prediction model from process construction, parameter selection, and sampling, and randomly generated 501 samples of patients from the emergency database for cluster analysis (Ward’s method and K-means) and decision trees analysis upon data mining. The findings of this study show that the triage categorization of nurses is higher than that of doctors and most abnormal diagnoses occur to patients not examined on the date of admittance. The vital signs of pulse and temperature are more discerning. According to the confidence and support proportion, this study proposed seven association rules.
T cell peptide of a self-protein elicits autoantibody to the protein antigen. Implications for specificity and pathogenetic role of antibody in autoimmunity. (1993)

A 13-mer peptide of the ZP3 glycoprotein from mouse zona pellucida has a T cell epitope that induces autoimmune oophoritis and a B cell epitope that reacts with antibody to murine ZP3. When the B cell epitope was partially truncated, the ZP3 peptides no longer induced antibody to the B cell epitope, but unexpectedly they elicited antibody to the zona pellucida. These autoantibodies were of IgG class, detected in sera and bound to the ovarian zona pellucida. That an exclusive T cell peptide of murine ZP3, without coinjection of the whole ZP3 protein, elicited autoantibodies against ZP3 outside the T cell peptide was confirmed as follows. First, the ZP3 T cell peptide did not contain additional B cell epitopes that cross-reacted with native ZP3. Second, endogenous ovarian Ag were required because autoantibodies were not detected in ovariectomized mice immunized with ZP3 peptides lacking the B epitope. This autoantibody amplification phenomenon demonstrates conclusively that 1) self-reactive B cells for ovarian autoantigens respond to endogenous ovarian Ag in vivo after activation of ZP3-specific Th cells and 2) serum antibody in an autoimmune disease need not mirror the immunogen that initiates the disease process. Nonetheless, the autoantibodies bound to the zona pellucida in vivo and are potentially important in disease pathogenesis.
CpG and double-stranded RNA trigger human NK cells by Toll-like receptors: Induction of cytokine release and cytotoxicity against tumors and dendritic cells (2004)

Toll-like receptors (TLRs) are pattern-recognition receptors responsible for triggering cells of innate immunity. In this study we investigated the expression and function of TLRs 3 and 9 in human natural killer (NK) cells. In the presence of IL-12, freshly isolated NK cells responded to double-stranded RNA or unmethylated CpG DNA and expressed CD69 and CD25 activation markers. Because both markers were expressed by virtually all NK cells, this would suggest that most of them can be triggered by TLRs. Remarkably, NK cell stimulation also resulted in the induction of their functional program as revealed by IFN-gamma and tumor necrosis factor-alpha release and by up-regulation of cytolytic activity against tumor cells. IL-8 could efficiently substitute IL-12 in supporting NK cell responses to TLR-mediated stimulation. Importantly, freshly isolated NK cells acquired the ability to lyse immature dendritic cells after stimulation with double-stranded RNA and IL-12. However, responses to these stimuli were not restricted to fresh NK cells, because significant responses were also detected in polyclonal NK cells cultured in the presence of exogenous IL-2 for several weeks. The analysis of NK cell clones revealed some degree of heterogeneity in the ability to respond to TLR stimulation also among NK clones derived from a single donor. These data suggest that stimuli acting on TLR not only activate immature dendritic cells to release IL-12 but also render NK cells capable of receiving triggering signals from pathogen-associated molecules, thus exerting a regulatory control on the early steps of innate immune responses against infectious agents.
Removal of antibiotic growth promoters from poultry diets: implications and strategies to minimise subsequent problems (2000)

Studies with germ-free chicks and antimicrobial compounds have indicated the significance of the interaction between host nutrition and the intestinal microflora. This interaction has suddenly leapt to prominence as a result of the decision of the European Union to remove several antibacterial agents from use in animal feed. A consequence of this decision has been a loosening of some of the constraints on intestinal bacterial growth rates which will benefit from the use of slowly digested ingredients, because undigested feed is a potential substrate for bacterial fermentation. The use of poorly digestible ingredients runs the risk not only of poor performance, which has always been the case, but now there is an additional danger from bacterial overgrowth and subsequent disease/intestinal disorders. Variations in the nutritional quality of the ingredients are therefore of increased relevance, and any measures that reduce such variations are likely to be of benefit. As a result, the use of enzymes, which are known to reduce variations in the performance of birds fed on barley-, wheat- and maize-based diets, will need to be revisited, particularly with reference to correct dosage. In the past the use of antibiotics effectively reduced the need to consider enzyme use and dose. Coccidiosis control is also of great interest because of its association with necrotic enteritis. Prevention of coccidiosis and limitation of the damage to the intestines associated with this disease is of paramount importance if necrotic enteritis is subsequently to be avoided. As a result, the use of coccidiostats for direct control and betaine and other pronutrients for amelioration of the symptoms is receiving greater attention. Ultimately it is hoped that nutritional control will lead to microbiological control, allowing for more consistent production responses in the absence of antibiotics.
DNA Nanotechnology Grows Up (2011)

Once dismissed as molecular parlor tricks, techniques for piecing ultrasmall structures together with DNA are starting to prove their worth in serious research.
Combination of Trastuzumab and Tanespimycin (17-AAG, KOS-953) Is Safe and Active in Trastuzumab-Refractory HER-2–Overexpressing Breast Cancer: A Phase I Dose-Escalation Study (2007)

Tanespimycin plus trastuzumab is well tolerated and has antitumor activity in patients with HER-2+ breast cancer whose tumors have progressed during treatment with trastuzumab. These data suggest that Hsp90 function can be inhibited in vivo to a degree sufficient to cause inhibition of tumor growth.