gebhart/patrepeval huggingface dataset:
Controlling Subtilisin Activity and Selectivity in Organic Media by Imprinting with Nucleophilic Substrates (1997)

The activity and substrate specificity of subtilisin-catalyzed acylation of nucleosides in organic solvents can be controlled by lyophilizing the enzyme from an aqueous solution containing the substrate. This “molecular imprinting” technique was examined using thymidine as a model nucleoside, and the resulting subtilisin preparation was up to 50-fold more reactive toward thymidine acylation in nearly anhydrous tetrahydrofuran than subtilisin lyophilized from aqueous buffer in the absence of the nucleoside. Although several compounds lyophilized with subtilisin, including thymine and ribose, improved the rate of thymidine acylation, the thymidine-imprinted enzyme was the most efficient catalyst for this reaction. Furthermore, it was possible to alter the substrate selectivity of subtilisin by lyophilizing the enzyme in the presence of a different nucleophilic substrate. For example, imprinting made possible the discrimination between structurally different (i.e., sucrose versus thymidine) as well as structurally similar (i.e., thymidine versus deoxyadenosine) nucleophiles. Molecular modeling studies of the interaction of thymidine or the unrelated sucrose with subtilisin revealed that structural changes upon imprinting in the serine protease's catalytic triad may be responsible for the observed activation and selectivity changes. Further use of molecular dynamics indicated that structural changes in the catalytic triad occur during imprinting, and that these changes may be the major factor that contributes to imprinting-induced substrate selectivity. This contrasts with the previously held notion that imprinting influences mainly substrate binding.
Targeted disruption of the murine lecithin:cholesterol acyltransferase gene is associated with reductions in plasma paraoxonase and platelet-activating factor acetylhydrolase activities but not in apolipoprotein J concentration (1999)

Lecithin:cholesteryl acyltransferase (LCAT) deficiency resulting from targeted disruption of the Lcat gene in the mouse is associated with dramatic decreases in HDL concentration and the accumulation of nascent HDL in the plasma. We examined whether LCAT deficiency in mice is associated with a concomitant decrease in two antioxidative enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH). In control Lcat (+/+) mice both these enzymes are transported on HDL. Compared to Lcat (+/+) mice, HDL-cholesterol is reduced 94% and apoA-I, 90%, in Lcat (-/-) mice; this reduction in HDL is paralleled by a 71% decrease in PAF-AH activity and in a 58% decrease in PON activity. Apolipoprotein J (apoJ) levels, rather than being decreased, were significantly (P = 0.01) higher (36%) in Lcat (-/-) than in Lcat (+/+) mice, and the apo J/PON ratio was 3-fold greater in Lcat (-/-) than in Lcat (+/+) animals. Even though apolipoprotein A-I (apoA-I) concentration and PON activity were drastically reduced, there was no reduction in apoA-I and PON liver mRNA levels suggesting that post-transcriptional events are responsible for the reduction of plasma PON and apoA-I levels. Fast protein liquid chromatography (FPLC) revealed that in Lcat (+/+) mice both PON and PAF-AH activity is associated with large, apoA-I-containing HDL particles (9.7 nm by non-denaturing gradient gel electrophoresis) while in Lcat (-/-) mice both enzymes are associated with small 8.2 nm particles. We conclude that the concomitant reduction in HDL and apoA-I concentrations and PON and PAF-AH activities is best explained by rapid clearance of the small HDL particles found in LCAT deficiency.
Using the Global Positioning System (GPS) to fulfill the position/location requirements of the National Training Center (NTC) and other U.S. Army instrumented testing and training ranges. (1991)

This thesis discusses the use of the Global Positioning System (GPS) to fulfill requirements for exact position/location (P/L) of combat elements on Army testing and training ranges. These requirements include the control of the ranges, measuring effectiveness of employing new systems or doctrine, use in after action reviews (AARs) to discuss battlefield events, recording operations for later analysis, and safety. It also addresses use of GPS equipped systems by the player units while participating in simulated combat on these ranges. The National Training Center (NTC) at Fort Irwin, California, is currently the largest and most complex of the Army's instrumented ranges. It is referred to throughout this thesis for examples of P/L requirements and instrumentation capabilities. The development and fielding of GPS has added a new dimension in the Army's ability to accurately measure and record P/L. The designers of future instrumentation upgrades are incorporating GPS capabilities. This thesis will show how capabilities can be improved and money saved by using a coordinated effort when employing GPS on the Army's instrumented ranges.
Comparative Protein Structure Modeling: Introduction and Practical Examples with Modeller (2003)

A useful three-dimensional (3D) model for a protein of unknown structure (the target) can frequently be built based on one or more related proteins of known structure (the templates). This is the aim of comparative or homology protein structure modeling. The necessary conditions are that the similarity between the target sequence and the template structures is detectable and that the correct alignment between them can be constructed. For reviews of comparative modeling, see refs. , , , , . This approach to structure prediction is possible because a small change in the protein sequence usually results in a small change in its 3D structure (,).
BiMOS modeling for reliable SOI circuit design (2002)

Summary form only given. Recent work has clearly revealed that transient current in the parasitic bipolar junction transistor (BJT) of the floating-body SOI MOSFET can be significant and degrading even in SOI circuits operating at voltages well below the BJT-defined drain-source breakdown. The BJT is also critically important with regard to soft errors in low-voltage SOI memory circuits. In these cases, the BJT current is driven by dynamic charging of the body and concomitant forward biasing of the source (or drain) junction, supported by capacitive, or charge coupling between the BJT and the MOSFET. A reliable circuit model for the floating-body SOI MOSFET must therefore account for the coupled BJT. In this paper we present a new, quasi-2D parasitic BJT model physically coupled to the SOISPICE MOSFET models and defined in terms of their parameters. We further use physical insight derived from this BiMOS modeling to identify a new means of controlling the transient BJT, or leakage current in SOI MOSFETs which could be exploited in design.
Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies (2001)

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 x 10(7)/kg (range, 1.01 x 10(7)/kg to 4.96 x 10(7)/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 x 10(9)/L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 x 10(9)/L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P =.01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor.
Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia (2000)

The hallmark of chronic myeloid leukemia (CML) is the BCR-ABL fusion gene, which is usually formed as a result of the t(9;22) translocation. Patients with CML show considerable heterogeneity both in their presenting clinical features and in the time taken for evolution to blast crisis. In this study, metaphase fluorescence in situ hybridization showed that a substantial minority of patients with CML had large deletions adjacent to the translocation breakpoint on the derivative 9 chromosome, on the additional partner chromosome in variant translocations, or on both. The deletions spanned up to several megabases, had variable breakpoints, and could be detected by microsatellite polymerase chain reaction in unfractionated bone marrow and purified peripheral blood granulocytes. The deletions were likely to occur early and possibly at the time of the Philadelphia (Ph) chromosome translocation: deletions were detected at diagnosis in 11 patients, were found in all Ph-positive metaphases, and were more prevalent in patients with variant Ph chromosomes. Kaplan-Meier analysis showed a median survival time of 36 months in patients with a deletion; patients without a detectable deletion survived > 90 months. The survival-time difference was significant on log-rank analysis (P =. 006). Multivariate analysis demonstrated that the prognostic importance of deletion status was independent of age, sex, percentage of peripheral blood blasts, and platelet count. Our data therefore suggest that an apparently simple, balanced translocation may result not only in the generation of a dominantly acting fusion oncogene but also in the loss of one or more genes that influence disease progression. (Blood. 2000;95:738-743)
The influence of female gender on cardiac arrest outcomes: a systematic review of the literature (2014)

In the reported literature female gender seems to offer survival and outcome advantages following out-of-hospital cardiac arrest over male gender. This is in contrast to most other aspects of heart disease in which women tend to have a worse prognosis.
Rupture of the Anterior Tibial Tendon: Three Clinical Cases, Anatomical Study, and Literature Review (2006)

According to literature, surgical repair is the treatment of choice for acute ruptures and for patients with high activity levels. For chronic ruptures and patients with low demands, conservative management may lead to an equally good outcome. Knowledge of the anatomy in this region may be helpful for diagnosis and for the interpretation of intraoperative findings and choosing the most appropriate surgical procedure.
Gene therapy for asthma (2003)

The accessibility of the airway epithelium and the limitations of current treatments for asthma make the disease a logical target for gene therapy. Study of the immunopathology of chronic airway inflammation has recently identified several pathways that lead to the maladaptive, antigen-induced polarization of CD4+ T cells to a type-2 phenotype. This polarization is thought to lead to IgE production and eosinophil recruitment and activation that is associated with epithelial cell injury and airway hyper-reactivity. Gene transfer to the bronchial epithelium has been used in experimental models to redirect these pathways toward a less injurious, type-1 phenotype. This mini-review highlights recent mechanism-based immunomodulatory and supportive gene transfer approaches to treat animal models of asthma. Although substantial hurdles to airway gene transfer remain, gene transfer offers the possibility of interrupting the pathophysiology of airway inflammation. Doing so can be expected to yield long-lasting protection from bronchospastic challenge and reduced dependence on inhaled and oral medications.
Mechanism of fibrin coagulation based on selective, cation‐driven, protofibril association (1988)

Abstract The cation sensitivity of linear and lateral assembly processes of thrombin‐ and reptilase‐activated fibrinogen was examined. Analytic ultracentrifugation shows that the linear assembly of fibrin oligomers (protofibrils) is neither cation dependent nor sensitive to chelating agents. Protofibrils generated with thrombin–hirudin gelate with either 1–2 mM Ca(II) or 15–100 μ M Zn(II). By contrast, protofibril B, generated with reptilase–diisopropylfluorophosphonate, gelates only with Ca(II) but is insensitive to Zn(II). These results indicate that the release of fibrinopeptides A and B (FPA and FPB) expose two types of lateral binding sites that are sensitive to Ca(II) and Zn(II) respectively. Transmission electron (TEM) micrographs of negatively stained gels indicate that the linear packing of the monomers within the fibrin‐ and cation‐induced protofibrin fibers is essentially identical. Scanning electron (SEM) micrographs show that the Ca(II)‐induced protofibrin B gel is similar to fibrin. In all, it seems that branching and gelation derive from two types of cation‐sensitive, lateral associative processes. Based on these findings, a new paradigm for fibrin coagulation is proposed.
Tamoxifen enhances cell death in implanted MCF7 breast cancer by inhibiting endothelium growth. (1994)

Magnetic resonance imaging at high spatial resolution and histochemical staining were applied to monitor the influence of tamoxifen versus estrogen on the growth, endothelial density, and extent of necrosis in tumors of MCF7 human breast cancer cells implanted in nude mice. Concomitantly with tamoxifen growth arrest, a highly significant decrease, by more than 2-fold, in the endothelial density of viable tumor regions had occurred, together with a significant increase in the extent of necrosis. The results suggest that the antiestrogenic activity of tamoxifen in breast cancer, which results in enhanced necrosis and tumor regression, is due to the inhibition of angiogenesis and of endothelial growth, thus reducing vascularization and impairing tumor perfusion.
Processing of the gp55-116 envelope glycoprotein complex (gB) of human cytomegalovirus (1989)

The processing pathway of the major envelope glycoprotein complex, gp55-116 (gB), of human cytomegalovirus was studied using inhibitors of glycosylation and endoglycosidases. The results of these studies indicated that the mature gp55-116 is synthesized by the addition of both simple and complex N-linked sugars to a nonglycosylated precursor of estimated Mr 105,000. In a rapid processing step, the Mr 105,000 precursor is glycosylated to a protein of Mr 150,000 (gp150) which contains only endoglycosidase H-sensitive sugar linkages. The gp150 is then processed relatively slowly to a Mr 165,000 to 170,000 species (gp165-170), which is then cleaved to yield the mature gp55-116. Monensin prevented the final processing steps of the gp150, including cleavage, suggesting that transport through the Golgi apparatus is required for complete processing. Digestion of the intracellular forms of this complex as well as the virion forms confirmed the above findings and indicated that the mature virion form of gp55 contains 8,000 daltons of N-linked sugars. The virion gp116 contains some 52,000 to 57,000 daltons of N-linked carbohydrates and approximately 5,000 daltons of O-linked sugars.
Ondansetron for Reduction of Drinking Among Biologically Predisposed Alcoholic Patients (2000)

Our results suggest that ondansetron (particularly the 4 microg/kg twice per day dosage) is an effective treatment for patients with early-onset alcoholism, presumably by ameliorating an underlying serotonergic abnormality. JAMA. 2000;284:963-971
Tumor-specific cytotoxic T cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells transfected with polymorphic epithelial mucin complementary DNA. (1993)

Human breast and pancreatic adenocarcinomas are tumors of ductal epithelial cell origin and as such produce and express on their surface polymorphic epithelial cell mucin encoded by the MUC 1 gene. We have previously reported that tumor-specific cytotoxic T cells derived from patients bearing such tumors recognize specific epitopes on the mucin polypeptide core. This recognition was not MHC-restricted because of the highly repetitive sequence of the polypeptide core, which allows simultaneous recognition of many identical epitopes, and cross-linking and aggregation of TCR on mucin-specific T cells. Those studies were performed with limited numbers of tumor cells or allogeneic tumor cell lines. A renewable source of autologous cells presenting this Ag was necessary to further explore mucin-specific immunity. We report here successful establishment and functional analysis of mucin-specific CTL lines and clones derived from breast and pancreatic cancer patients, using either autologous or allogeneic mucin-transfected B cells as Ag. Our results demonstrate that transfection of autologous or allogeneic B cells with mucin confers upon them tumor Ag-presenting ability as well as susceptibility to lysis by mucin-specific CTL. Transfection of APC with this or any other human tumor Ag that may be molecularly defined in the future provides a unique and powerful tool with which to examine the ability of a tumor-associated Ag to stimulate T cell responses.
The group A streptococcal virR49 gene controls expression of four structural vir regulon genes (1995)

Within a genomic locus termed the vir regulon, virR genes of opacity factor-nonproducing (OF-) group A streptococci (GAS) are known to control the expression of the genes encoding M protein (emm) and C5a peptidase (scpA) and of virR itself. Within the corresponding genomic locus, opacity factor-producing (OF+) GAS harbor additional emm-related genes encoding immunoglobulin G- and immunoglobulin A-binding proteins (fcrA and enn, respectively). The virR gene region of the OF+ GAS M-type 49 strain CS101 was amplified by PCR, and 2,650 bp were directly sequenced. An open reading frame of 1,599 bp exhibited 76% overall homology to published virR sequences. By utilizing mRNA analysis, the 5' ends of two specific transcripts were mapped 370 and 174 bp upstream of the start codon of this open reading frame. The deduced sequences of the corresponding promoters and their locations differed from those of previously reported virR promoters. Transcripts from wild-type fcrA49, emm49, enn49, and scpA49 genes located downstream of virR49 were characterized as being monocistronic. The transcripts were quantified and mapped for their 5' ends. Subsequently, the virR49 gene was inactivated by specific insertion of a nonreplicative pSF152 vector containing recombinant virR49 sequences. The RNA from the resulting vir-mut strain did not contain transcripts of virR49, fcrA49, emm49, or enn49 and contained reduced amounts of the scpA49 transcript when compared with wild-type RNA. The mRNA control from the streptokinase gene was demonstrated not to be affected. When strain vir-mut was rotated in human blood, it was found to be fully sensitive to phagocytosis by human leukocytes. Thus, the present study provides evidence that virR genes in OF+ GAS could be involved in the control of up to five vir regulon genes, and their unaffected regulatory activity is associated with features postulated as crucial for GAS virulence.
Voltage-dependent voltage-acceleration of oxide breakdown for ultra-thin oxides (2002)

We report the voltage-dependence of voltage acceleration for ultra-thin oxides from 2.2 V to 5 V over a range of T/sub ox/ values from 1.7 nm to 5.0 nm. This unique behavior manifest itself as a power-law voltage-dependence for time-to-breakdown (T/sub BD/) over a variety of experimental observations. Using the concept of energy-to-breakdown, we explore the possible scenarios such as fractional energy or defect generation probability as a function of voltage to account for the increase in voltage acceleration with decreasing voltages.
Nanocubes for Real-Time Exploration of Spatiotemporal Datasets (2013)

Consider real-time exploration of large multidimensional spatiotemporal datasets with billions of entries, each defined by a location, a time, and other attributes. Are certain attributes correlated spatially or temporally? Are there trends or outliers in the data? Answering these questions requires aggregation over arbitrary regions of the domain and attributes of the data. Many relational databases implement the well-known data cube aggregation operation, which in a sense precomputes every possible aggregate query over the database. Data cubes are sometimes assumed to take a prohibitively large amount of space, and to consequently require disk storage. In contrast, we show how to construct a data cube that fits in a modern laptop's main memory, even for billions of entries; we call this data structure a nanocube. We present algorithms to compute and query a nanocube, and show how it can be used to generate well-known visual encodings such as heatmaps, histograms, and parallel coordinate plots. When compared to exact visualizations created by scanning an entire dataset, nanocube plots have bounded screen error across a variety of scales, thanks to a hierarchical structure in space and time. We demonstrate the effectiveness of our technique on a variety of real-world datasets, and present memory, timing, and network bandwidth measurements. We find that the timings for the queries in our examples are dominated by network and user-interaction latencies.
Dissection of Multibeam Satellite Communications with a Large-scale Antenna System Toolbox (2014)

Current multibeam satellite systems consist of a very large number of spot beams. In this paper, we analyze them from the large scale MIMO perspective, and establish a comparison with massive MIMO systems. It will be shown that the large number of beams has important operational implications, and that it simplifies the analysis because it allows using asymptotic results. However, it will also be shown that current multibeam satellite links, despite their large number of antennas, do not qualify as massive MIMO systems.