gebhart/patrepeval huggingface dataset:
When should we measure lipoprotein (a)? (2013)

Recently published epidemiological and genetic studies strongly suggest a causal relationship of elevated concentrations of lipoprotein (a) [Lp(a)] with cardiovascular disease (CVD), independent of low-density lipoproteins (LDLs), reduced high density lipoproteins (HDL), and other traditional CVD risk factors. The atherogenicity of Lp(a) at a molecular and cellular level is caused by interference with the fibrinolytic system, the affinity to secretory phospholipase A2, the interaction with extracellular matrix glycoproteins, and the binding to scavenger receptors on macrophages. Lipoprotein (a) plasma concentrations correlate significantly with the synthetic rate of apo(a) and recent studies demonstrate that apo(a) expression is inhibited by ligands for farnesoid X receptor. Numerous gaps in our knowledge on Lp(a) function, biosynthesis, and the site of catabolism still exist. Nevertheless, new classes of therapeutic agents that have a significant Lp(a)-lowering effect such as apoB antisense oligonucleotides, microsomal triglyceride transfer protein inhibitors, cholesterol ester transfer protein inhibitors, and PCSK-9 inhibitors are currently in trials. Consensus reports of scientific societies are still prudent in recommending the measurement of Lp(a) routinely for assessing CVD risk. This is mainly caused by the lack of definite intervention studies demonstrating that lowering Lp(a) reduces hard CVD endpoints, a lack of effective medications for lowering Lp(a), the highly variable Lp(a) concentrations among different ethnic groups and the challenges associated with Lp(a) measurement. Here, we present our view on when to measure Lp(a) and how to deal with elevated Lp(a) levels in moderate and high-risk individuals.
Micro active guide wire catheter system (2002)

We propose a new prototype model of micro-active guide wire catheter that has two bending degrees of freedom. The fabrication methods of this micro-active catheters (MAC) are described. Prototype models are 3Fr, 4Fr, 6Fr (1Fr=1 mm) in diameter and consist of catheter tube and active guide wire with ionic conducting polymer film on its front end as the servo actuator. The bending characteristics of the MAC have been measured by application of electricity in physiological saline solution. By using simulators (whose conditions are similar to those of a body cavity), we carried out simulation experiments "in vitro" and the contrast experiments of operability between the proposed catheter and a conventional guide wire catheter. The experimental results indicate that the proposed MAC is applicable to intracavity operations.
Gene Expression Classification of Colon Cancer into Molecular Subtypes: Characterization, Validation, and Prognostic Value (2013)

We describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways.
Rapid induction of apoptosis by cell-to-cell transmission of human immunodeficiency virus type 1 (1995)

The kinetics of human immunodeficiency virus type 1 (HIV-1)-induced cell death were investigated in cell-to-cell and cell-free models of virus transmission. Cocultivation of HIV-1 chronically infected H9 donor cells with uninfected H9 recipient cells resulted in rapid induction of programmed cell death. Within 8 h, apoptotic chromatin condensation was identified by histologic staining. In addition, many single cells with apoptotic nuclei were observed, indicating that stable cell fusion was not a requirement for apoptosis to occur. By 12 to 18 h of coculture, a DNA fragmentation ladder characteristic of apoptosis was detected by agarose gel electrophoresis. Quantitation of apoptosis by measurement of nuclear DNA content revealed that at least 20 to 30% of the nuclei were undergoing apoptosis by 24 h after cocultivation. The appearance of condensed nuclei and fragmented DNA occurred as HIV reverse transcription was completed, and it was not inhibited by zidovudine, suggesting that induction of apoptosis did not require new HIV replication. Soluble CD4 inhibited apoptosis, demonstrating that Env-CD4 interactions were required for apoptosis. In contrast to that in cell-to-cell transmission, apoptosis in cell-free HIV infections was markedly inefficient and was not observed until 70 to 90 h after infections were initiated. These findings indicate that HIV-1 induction of programmed destruction of the nucleus is initiated at the time of cell-cell cocultivation by a mechanism which requires CD4-Env interactions but not new HIV replication.
Immature dendritic cells kill ovarian carcinoma cells by a FAS/FASL pathway, enabling them to sensitize tumor-specific CTLs (2001)

Dendritic cells (DCs) can acquire antigen(s) from apoptotic tumor cells, resulting in an immunogen that can induce class I-restricted cytotoxic T lymphocytes (CTLs) and protective tumor rejection. Here, we investigated whether DCs derived from ascitic monocytes of patients with ovarian carcinoma could kill autologous ovarian tumor cells and if as a result they would acquire antigen(s) enabling them to induce a tumor-specific immunity. We found that the immature DCs could exert a significant cytotoxicity towards autologous and allogeneic ovarian tumor cells. This cytotoxicity was independent of Ca(2+) and could be inhibited by anti-Fas IgG1 monoclonal antibody, indicating the involvement of the Fas/Fas ligand (FasL) pathway in the cytotoxic mechanism. Further supporting this conclusion, the ascitic monocyte-derived DCs expressed high levels of FasL mRNA and intracellular FasL and significant levels of Fas were also revealed on the surface of ovarian tumor cells. Coculture of DCs induced apoptosis in ovarian carcinoma cells, as well as uptake of apoptotic tumor cells into the cytoplasma of the DCs, as visualized by immunofluoresence. Autologous DCs cocultured with apoptotic ovarian tumor cells were able to specifically stimulate tumor-specific CTLs, whereas DCs cocultured with necrotic ovarian cells were unable to do so. Collectively, these results demonstrate that immature DCs can kill autologous ovarian carcinoma cells via the Ca(2+)-independent Fas/FasL pathway and that this may have important consequences for their ability to stimulate tumor-specific CTLs.
Biosynthetic Intermediate Analysis and Functional Homology Reveal a Saxitoxin Gene Cluster in Cyanobacteria (2008)

Saxitoxin (STX) and its analogues cause the paralytic shellfish poisoning (PSP) syndrome, which afflicts human health and impacts coastal shellfish economies worldwide. PSP toxins are unique alkaloids, being produced by both prokaryotes and eukaryotes. Here we describe a candidate PSP toxin biosynthesis gene cluster (sxt) from Cylindrospermopsis raciborskii T3. The saxitoxin biosynthetic pathway is encoded by more than 35 kb, and comparative sequence analysis assigns 30 catalytic functions to 26 proteins. STX biosynthesis is initiated with arginine, S-adenosylmethionine, and acetate by a new type of polyketide synthase, which can putatively perform a methylation of acetate, and a Claisen condensation reaction between propionate and arginine. Further steps involve enzymes catalyzing three heterocyclizations and various tailoring reactions that result in the numerous isoforms of saxitoxin. In the absence of a gene transfer system in these microorganisms, we have revised the description of the known STX biosynthetic pathway, with in silico functional inferences based on sxt open reading frames combined with liquid chromatography-tandem mass spectrometry analysis of the biosynthetic intermediates. Our results indicate the evolutionary origin for the production of PSP toxins in an ancestral cyanobacterium with genetic contributions from diverse phylogenetic lineages of bacteria and provide a quantum addition to the catalytic collective available for future combinatorial biosyntheses. The distribution of these genes also supports the idea of the involvement of this gene cluster in STX production in various cyanobacteria.
In situ triaxial magnetic field compensation for the spin-exchange-relaxation-free atomic magnetometer (2012)

The spin-exchange-relaxation-free (SERF) atomic magnetometer is an ultra-high sensitivity magnetometer, but it must be operated in a magnetic field with strength less than about 10 nT. Magnetic field compensation is an effective way to shield the magnetic field, and this paper demonstrates an in situ triaxial magnetic field compensation system for operating the SERF atomic magnetometer. The proposed hardware is based on optical pumping, which uses some part of the SERF atomic magnetometer itself, and the compensation method is implemented by analyzing the dynamics of the atomic spin. The experimental setup for this compensation system is described, and with this configuration, a residual magnetic field of strength less than 2 nT (±0.38 nT in the x axis, ±0.43 nT in the y axis, and ±1.62 nT in the z axis) has been achieved after compensation. The SERF atomic magnetometer was then used to verify that the residual triaxial magnetic fields were coincident with what were achieved by the compensation system.
Oligomeric proanthocyanidin complexes: history, structure, and phytopharmaceutical applications. (2000)

Considerable recent research has explored therapeutic applications of oligomeric proanthocyanidin complexes (OPCs), naturally occurring plant metabolites widely available in fruits, vegetables, nuts, seeds, flowers, and bark. OPCs are primarily known for their antioxidant activity. However, these compounds have also been reported to demonstrate antibacterial, antiviral, anticarcinogenic, anti-inflammatory, anti-allergic, and vasodilatory actions. In addition, they have been found to inhibit lipid peroxidation, platelet aggregation, capillary permeability and fragility, and to affect enzyme systems including phospholipase A2, cyclooxygenase, and lipoxygenase. Based on these reported findings, OPCs may be a useful component in the treatment of a number of conditions.
Time-scale modification of speech signals using cross-correlation functions (1992)

A high-performance method of modifying the time scale of speech signals into an arbitrary time scale was developed. It requires substantially reduced arithmetic operations. This process is performed within a time domain where the time-scale expansion or compression is performed by inserting or substituting composite segments into or from an original input signal, and the length of the segment is optimized by an objective evaluation process. A monosyllable articulation test comparing this method with a conventional time-scale modification method performed by a simple modification of sampling frequency proved that there are definite advantages to using the new method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
High-Fidelity In Vitro Recombination Using a Proofreading Polymerase (2001)

We describe a convenient PCR-based protocol for in vitro recombination of homologous genes, thereby minimizing the rate of associated point mutations. High-fidelity recombination conditions were obtained using Vent DNA polymerase, which, in contrast to Taq DNA polymerase, shows significant proofreading activity and ranges among the slowest thermostable DNA polymerases, allowing tight control of the polymerase-catalyzed DNA extension. To determine the mutagenesis rate and to analyze the efficiency of recombination, 89 clones from a standard experiment were randomly selected for further analysis. Sequence comparison revealed that 21% (19/89) of the clones result from different recombination events in the marker-containing region (260 bp). The overall mutation rate is only 0.02%, which is the lowest rate thus far reported for in vitro recombination experiments.
The High Molecular Weight Subunits Of Wheat, Barley And Rye: Genetics, Molecular Biology, Chemistry And Role In Wheat Gluten Structure And Functionality (1990)

Abstract Although almost unheard of only a decade ago, the High Molecular Weight subunits of wheat glutenin have since become the most intens¬ ively studied group of wheat proteins. This is in spite of the fact that they account for only about 5% of the total proteins of the mature grain. This sudden interest resulted from the demonstration by Payne and coworkers at the Plant Breeding Institute (Cambridge, UK) that allelic variation in the polypeptide composition of the HMW subunits was closely correlated with the breadmaking quality of European cultivars of wheat, and of the progeny of crosses between them (Payne et al. 1979; 1981a). These observations have since been confirmed and extended in a number of other laboratories and countries and “subunit screening” is now routinely used in many plant breeding program mes.
Physiological Characterization of the ARO10 -Dependent, Broad-Substrate-Specificity 2-Oxo Acid Decarboxylase Activity of Saccharomyces cerevisiae (2005)

Aerobic, glucose-limited chemostat cultures of Saccharomyces cerevisiae CEN.PK113-7D were grown with different nitrogen sources. Cultures grown with phenylalanine, leucine, or methionine as a nitrogen source contained high levels of the corresponding fusel alcohols and organic acids, indicating activity of the Ehrlich pathway. Also, fusel alcohols derived from the other two amino acids were detected in the supernatant, suggesting the involvement of a common enzyme activity. Transcript level analysis revealed that among the five thiamine-pyrophospate-dependent decarboxylases (PDC1, PDC5, PDC6, ARO10, and THI3), only ARO10 was transcriptionally up-regulated when phenylalanine, leucine, or methionine was used as a nitrogen source compared to growth on ammonia, proline, and asparagine. Moreover, 2-oxo acid decarboxylase activity measured in cell extract from CEN.PK113-7D grown with phenylalanine, methionine, or leucine displayed similar broad-substrate 2-oxo acid decarboxylase activity. Constitutive expression of ARO10 in ethanol-limited chemostat cultures in a strain lacking the five thiamine-pyrophosphate-dependent decarboxylases, grown with ammonia as a nitrogen source, led to a measurable decarboxylase activity with phenylalanine-, leucine-, and methionine-derived 2-oxo acids. Moreover, even with ammonia as the nitrogen source, these cultures produced significant amounts of the corresponding fusel alcohols. Nonetheless, the constitutive expression of ARO10 in an isogenic wild-type strain grown in a glucose-limited chemostat with ammonia did not lead to any 2-oxo acid decarboxylase activity. Furthermore, even when ARO10 was constitutively expressed, growth with phenylalanine as the nitrogen source led to increased decarboxylase activities in cell extracts. The results reported here indicate the involvement of posttranscriptional regulation and/or a second protein in the ARO10-dependent, broad-substrate-specificity decarboxylase activity.
Predicting data cache misses in non-numeric applications through correlation profiling (1997)

To maximize the benefit and minimize the overhead of software-based latency tolerance techniques, we would like to apply them precisely to the set of dynamic references that suffer cache misses. Unfortunately, the information provided by the state-of-the-art cache miss profiling technique (summary profiling) is inadequate for references with intermediate miss ratios - it results in either failing to hide latency, or else inserting unnecessary overhead. To overcome this problem, we propose and evaluate a new technique - correlation profiling - which improves predictability by correlating the caching behavior with the associated dynamic context. Our experimental results demonstrate that roughly half of the 22 non-numeric applications we study can potentially enjoy significant reductions in memory stall time by exploiting at least one of the three forms of correlation profiling we consider.
Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain genePitx3 (2004)

The mesencephalic dopamine (mesDA) system is involved in the control of movement and behavior. The expression of Pitx3 in the brain is restricted to the mesDA system and the gene is induced relatively late, at E11.5, a time when tyrosine hydroxylase (Th) gene expression is initiated. We show here that, in the Pitx3-deficient aphakia (ak) mouse mutant, the mesDA system is malformed. Owing to the developmental failure of mesDA neurons in the lateral field of the midbrain, mesDA neurons are not found in the SNc and the projections to the caudate putamen are selectively lost. However, Pitx3 is expressed in all mesDA neurons in control animals. Therefore, mesDA neurons react specifically to the loss of Pitx3. Defects of motor control where not seen in the ak mice, suggesting that other neuronal systems compensate for the absence of the nigrostriatal pathway. However, an overall lower activity was observed. The results suggest that Pitx3 is specifically required for the formation of the SNc subfield at the onset of dopaminergic neuron differentiation.
A small-molecule antagonist of LFA-1 blocks a conformational change important for LFA-1 function (2001)

Lymphocyte function-associated antigen (LFA)-1/intercellular adhesion molecule (ICAM)-1 interactions mediate several important steps in the evolution of an immune response. LFA-1 is normally expressed in a quiescent state on the surface of leukocytes and interacts weakly with its ligands ICAM-1, -2, and -3. LFA-1 activity may be regulated by receptor clustering and by increasing the affinity of LFA-1 for its ligands. Affinity modulation of LFA-1 has been shown to occur via a conformational change in the LFA-1 heterodimer that can be detected by using monoclonal antibody 24 (mAb24). We have recently described a small-molecule antagonist of LFA-1, BIRT 377, that demonstrates selective in vitro and in vivo inhibition of LFA-1/ICAM-1-mediated binding events. We now demonstrate that BIRT 377 blocks the induction of the mAb24 reporter epitope on LFA-1 on the surface of SKW-3 cells treated with various agonists known to induce high-affinity LFA-1. These data imply that BIRT 377 exerts its inhibitory effects by preventing up-regulation of LFA-1 to its high-affinity conformation.
Strategies for induction, autologous hematopoietic stem cell transplantation, consolidation, and maintenance for transplantation-eligible multiple myeloma patients (2013)

There have been major advances in the past decade in the continuum of therapy for transplantation-eligible multiple myeloma patients. For patients requiring therapy, recommended induction treatment consists of triple drug regimens followed by the collection of hematopoietic stem cells. The question of early versus delayed transplantation is under investigation and may identify patients for whom early transplantation is optimal therapy and those for whom it may be delayed. For transplantation-eligible patients, high-dose melphalan remains the standard regimen. After transplantation, consolidation can be considered for patients with less than a complete remission. Maintenance therapy with bortezomib or lenalidomide (or both in very-high-risk patients) is a reasonable option for long-term disease control and improvement in overall survival. Incorporation of new agents into the continuum of multiple myeloma care should result in improved outcomes and long-term disease control.
Watershed Runoff and Erosion Modeling with a Hybrid Mesh Model (2008)

Distributed watershed modeling has gained popularity in recent years. Prevalent models in the United States include CASC2D and WEPP, among others. Although the existing models have been successful for some applications, a number of limitations exist. This paper presents a new watershed runoff and erosion model, SRH-W, with the aim to improve the numerical methods used by the existing models. The new model builds upon process features of the existing models such as CASC2D. However, a new representation of the watershed geometry with the zonal hybrid mesh is proposed, and a new solution technique with the conservative finite-volume formulation is implemented. The modeling concept and the mathematical and numerical formulations are first described. An illustrative case is then simulated to show some new features of the model. A number of verification and validation cases are also presented to demonstrate the model performance, accuracy, and efficiency. The new model is flexible, overcomes some shortcomings of the existing models, and performs well in the selected verification cases.
Sidelobe suppression in corrugated-waveguide filters (1977)

The reflection sidelobes of a corrugated optical waveguide filter are shown to be suppressed when the corrugation depth is tapered with a function that has low, Fourier-transform sidelobes. Several specific taper functions are considered, and sidelobe levels lower than −70 dB are shown to be feasible. A simple rule for estimating the 3-dB reflection bandwidth of a tapered corrugation is also presented.
Low nucleotide diversity in man. (1991)

The nucleotide diversity (pi) in humans is studied by using published cDNA and genomic sequences that have been carefully checked for sequencing accuracy. This measure of genetic variability is defined as the number of nucleotide differences per site between two randomly chosen sequences from a population. A total of more than 75,000 base pairs from 49 loci are compared. The DNA regions studied are the 5' and 3' untranslated regions and the amino acid coding regions. The coding regions are divided into nondegenerate sites (i.e., sites at which all possible changes are nonsynonymous), twofold degenerate sites (i.e., sites at each of which one of the three possible changes is synonymous) and fourfold degenerate sites (i.e., sites at which all three possible changes are synonymous). The pi values estimated are, respectively, 0.03 and 0.04% for the 5' and 3' UT regions, and 0.03, 0.06 and 0.11% for nondegenerate, twofold degenerate and fourfold degenerate sites. Since the highest pi value is only 0.11%, which is about one order of magnitude lower than those in Drosophila populations, the nucleotide diversity in humans is very low. The low diversity is probably due to a relatively small long-term effective population size rather than any severe bottleneck during human evolution.
An Architecture for Scalable and Manageable File Services (2001)

distributed file service, namespace, resource aggregation, manageability Monolithic file servers are limited by the power of an individual system. Cluster file servers are limited by resource sharing and recovery issues as the number of cluster nodes increases. DiFFS is a file service architecture that allows system resources to be added (or removed) dynamically, e.g., storage and processors. Resources are partitioned in such a way that contention is avoided, while maintaining a single namespace. Resources may be heterogeneous, and geographically dispersed. This architecture has several advantages. A file&amp;apos;s physical location is decoupled from its location in the namespace. This decoupling enables a powerful and flexible mechanism for the placement of file system objects. For example, different types of files, e.g., text or video, may reside anywhere in the namespace while being hosted by servers best suited to handling their content type. DiFFS also provides lightweight protocols for online dynamic reconfiguration (volume reassignment and object migration) to address fluctuating demand and potentially mobile file system entities. A DiFFS prototype has been implemented in Linux. Performance results indicate that the architecture achieves its flexibility and scalability goals without sacrificing performance.