gebhart/patrepeval huggingface dataset:
Site‐directed mutagenesis of the amino acid residues in β‐strand III [Val30‐Val36] of d‐amino acid aminotransferase of Bacillus sp. YM‐1 (1996)

The beta-strand III formed by amino acid residues Val30-Val36 is located across the active site of the thermostable D-amino acid aminotransferase (D-AAT) from thermophilic Bacillus sp. YM-1, and the odd-numbered amino acids (Tyr31, Val33, Lys35) in the strand are revealed to be directed toward the active site. Interestingly, Glu32 is also directed toward the active site. We first investigated the involvement of these amino acid residues in catalysis by alanine scanning mutagenesis. The Y31A and E32A mutant enzymes showed a marked decrease in k(cat) value, retaining less than 1% of the wild-type enzyme activity. The k(cat) values of V33A and K35A were changed slightly, but the Km of K35A for alpha-ketoglutarate was increased to 35.6 mM, compared to the Km value of 2.5 mM for the wild-type enzyme. These results suggested that the positive charge at Lys35 interacted electrostatically with the negative charge at the side chain of alpha-ketoglutarate. Site-directed mutagenesis of the Glu32 residue was conducted to demonstrate the role of this residue in detail. From the kinetic and spectral characteristics of the Glu32-substituted enzymes, the Glu32 residue seemed to interact with the positive charge at the Schiff base formed between the aldehyde group of pyridoxal 5'-phosphate (PLP) and the epsilon-amino group of the Lys145 residue.
Circadian Rhythm of Circulating Levels of the Endocannabinoid 2-Arachidonoylglycerol (2014)

The findings demonstrate that activity of the eCB system is profoundly modulated by circadian rhythmicity and suggest that its impact on the regulation of food intake is suppressed during sleep and is maximal during early to midafternoon.
Percutaneous implantation of pulmonary valves (2003)

Percutaneous implantation of valves is evolving as the most exciting innovation in transcatheter therapeutics. Valve repairs and replacements form an important indication of re-operations after congenital heart operations. Right ventricular outflow tract surgery is common after repair of conditions such as pulmonary atresia with Tetralogy of Fallot, common arterial trunk and Rastelli operation for transposition of great arteries, ventricular septal defect with pulmonary stenosis. Conduit survival is improving, nevertheless, re-operations are common. Although the re-operations can be performed at low risk, they still involve morbidity and mortality. Percutaneous implantation of valves is emerging as an alternative option for these group of patients. Our experience in percutaneous implantation of pulmonary valves has yielded encouraging results. For incompetence, the results are excellent. Evolving technology is making it applicable in wider clinical situations. Similar technology could also be applied to implantation of valves in the aortic position.
CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA (2014)

Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.
Direct kinematics of manipulators with hyper degrees of freedom and Frenet-Serret formula (2002)

The kinematic structure of a manipulator with hyper degrees of freedom is discussed from a theoretical viewpoint. Conditions for the kinematic structure are derived from a geometrically natural requirement that its direct kinematics tends to Frenet-Serret formula as its number of degrees of freedom increases. It is shown that the manipulator has to have two-degree-of-freedom joints, each of which consists of a twist and a one-directional bend.
Comprehensive health assessment and five‐yr follow‐up of allogeneic islet transplant recipients (2013)

In patients with type 1 diabetes mellitus (T1DM) complicated by severe hypoglycemic episodes, fear of hypoglycemia can significantly impact daily life. We evaluated whether restoration of glycemic awareness and prevention of hypoglycemia by islet allotransplant could reduce fear and improve health status. We conducted a comprehensive evaluation of patient-based outcomes in 48 T1DM subjects screened for allogeneic islet transplant alone (ITA) and 27 subjects who received an ITA. A battery of generic health status and diabetes-specific measures were used to assess ITA at evaluation, six months, and then annually after ITA. Allogeneic islet transplant was associated with a reduction in behaviors adopted in avoiding hypoglycemia (p Value < 0.001) and attenuation in concerns about hypoglycemic episodes (p Value < 0.001). Changes in hypoglycemia fear tracked most closely with insulin use. While there was a trend toward global improvement in health as measured by the EQ-5D (p Value = 0.002) and in depression symptoms as measured by the Beck (p Value = 0.003), physical health remained unchanged following ITA. Our findings support the socioemotional benefits of ITA during the five years after ITA, which to some extent remains dependent on preservation of islet graft function.
Introduction [Chapter 1] (2010)

The concept of sustainable management encompasses ecological, economic, and social criteria and indicators (C&I) for monitoring and assessing the association between maintaining a healthy rangeland base and sustaining the well-being of communities and economies. During a series of meetings from 2001 to 2003, the Sustainable Rangelands Roundtable (SRR) developed five criteria and 64 indicators of sustainable rangeland management. The SRR is a collaborative, inclusive organization, comprised of participants representing universities, federal research agencies, federal, state and local land management agencies, tribal governments, scientific societies, and both environmental and commodity-oriented non-governmental organizations. To achieve its goal, the SRR dealt with multiple issues, including those of scale and definitions. The Delphi technique was employed to maintain participant involvement between meetings and to help reach consensus about topics pertaining to the SRR's mission and the various indicators being considered. We used a six-point framework to develop indicators and standardize reporting upon them. One of the factors affecting indicator consideration was potential for obtaining data. To record attributes of various data sets in a way that allows summarizations and comparisons, SRR participants devised a data matrix that considered the kind of data, its grain and extent, applicable spatial and temporal scales, and various aspects of data quality. The SRR coordinated with other C&I programs in developing its suite of indicators. Applications and challenges to employing C&I for monitoring sustainable rangeland management are discussed.
Impaired Spatial Learning in α-Calcium-Calmodulin Kinase II Mutant Mice (1992)

Although long-term potentiation (LTP) has been studied as the mechanism for hippocampus-dependent learning and memory, evidence for this hypothesis is still incomplete. The mice with a mutation in the alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII), a synaptic protein enriched in the hippocampus, are appropriate for addressing this issue because the hippocampus of these mice is deficient in LTP but maintains intact postsynaptic mechanisms. These mutant mice exhibit specific learning impairments, an indication that alpha-CaMKII has a prominent role in spatial learning, but that it is not essential for some types of non-spatial learning. The data considerably strengthen the contention that the synaptic changes exhibited in LTP are the basis for spatial memory.
Vascular Permeability Factor, an Endothelial Cell Mitogen Related to PDGF (1989)

Vascular permeability factor (VPF) is a 40-kilodalton disulfide-linked dimeric glycoprotein that is active in increasing blood vessel permeability, endothelial cell growth, and angiogenesis. These properties suggest that the expression of VPF by tumor cells could contribute to the increased neovascularization and vessel permeability that are associated with tumor vasculature. The cDNA sequence of VPF from human U937 cells was shown to code for a 189-amino acid polypeptide that is similar in structure to the B chain of platelet-derived growth factor (PDGF-B) and other PDGF-B-related proteins. The overall identity with PDGF-B is 18%. However, all eight of the cysteines in PDGF-B were found to be conserved in human VPF, an indication that the folding of the two proteins is probably similar. Clusters of basic amino acids in the COOH-terminal halves of human VPF and PDGF-B are also prevalent. Thus, VPF appears to be related to the PDGF/v-sis family of proteins.
Expression cloning of a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase). (1994)

A cDNA encoding a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase) was obtained from an expression cDNA library of human melanoma cell line WM266-4 by enrichment of Namalwa KJM-1 cells highly expressing GD3 using an anti-GD3 antibody and a fluorescence-activated cell sorter. Selection of B-cell line Namalwa cells expressing transfected cDNAs in the presence of anti-GD3 monoclonal antibody KM641 gave a cDNA (pAMo-GD3) encoding a protein with a type II transmembrane topology as found for mammalian glycosyltransferases. The following evidence confirms that the cDNA encodes an alpha-2,8-sialyltransferase, which specifically converts GM3 to GD3. (i) Transfection of pAMo-GD3 into Namalwa KJM-1 cells leads to the appearance of GD3 and a GD3 synthase activity. (ii) Northern blot analysis revealed a correlation between the expression of this gene and GD3 in several cell lines. (iii) The putative COOH-terminal active domain of this cloned enzyme fused with protein A has been purified with IgG-Sepharose beads and has been shown to possess GD3-synthesizing activity, excluding the possibility that the cloned cDNA encodes a transacting factor inducing a GD3 synthase. The deduced primary sequence also contains the "sialyl motif" conserved among all the sialyltransferases cloned to date. The polymerase chain reaction analysis reveals that this gene is located on chromosome 12.
Export of microRNAs and microRNA-protective protein by mammalian cells (2010)

The discovery of microRNAs (miRNAs) as a new class of regulators of gene expression has triggered an explosion of research activities, but has left many unanswered questions about how this regulation functions and how it is integrated with other regulatory mechanisms. A number of miRNAs have been found to be present in plasma and other body fluids of humans and mice in surprisingly high concentrations. This observation was unexpected in two respects: first, the fact that these molecules are present at all outside the cell at significant concentrations and second, that these molecules appear to be stable outside of the cell. In light of this it has been suggested that the biological function of miRNAs may also extend outside of the cell and mediate cell-cell communication. We report here that after serum deprivation several human cell lines tested promptly export a substantial amount of miRNAs into the culture medium and the export process is largely energy dependent. The exported miRNAs are found both within and outside of the 16.5 and 120 K centrifugation pellets which contain most of the known cell-derived vesicles, the microvesicles and exosomes. We have identified some candidate proteins involved in this system, and one of these proteins may also play a role in protecting extracellular miRNAs from degradation. Our results point to a hitherto unrecognized and uncharacterized miRNA trafficking system in mammalian cells that is consistent with the cell-cell communication hypothesis.
Platelet Adhesion following the Administration of Tissue-type Plasminogen Activator and Its Reversal by Vitamin E in Rats (1996)

Thrombolytic therapy is known to induce platelet-related side effects. We used a parallel-plate flow chamber, which was connected to the femoral artery of the rat, to measure platelet adhesion ex vivo. A collagen-coated arterioarterial shunt between two carotid arteries was used to measure shunt patency duration as an index of antithrombotic efficacy. Tissue-type plasminogen activator (t-PA), vitamin E, and the combination of these two were intravenously administered for 60 min. Measurements were performed before drug administration, and at 30, 60, 120 min after the initiation of drug infusion. Our results indicated that (1) treatments with t-PA or t-PA/vitamin E prolonged the time to shunt occlusion at 30 and 60 min; (2) t-PA enhanced platelet adhesion at 60 and 120 min; (3) vitamin E tended to reduce platelet adhesion; (4) t-PA/vitamin E reduced the t-PA-enhanced platelet adhesion; (5) at the high-density area of platelet adhesion under t-PA treatment, the adherent platelets demonstrated severe morphological changes which could be blocked by vitamin E. These data suggest that t-PA may enhance platelet adhesion in rats and that this adverse effect can be suppressed by co-administration of vitamin E.
The health impact of chronic sinusitis in patients seeking otolaryngologic care (1995)

Although chronic sinusitis is an increasingly common diagnosis in the United States, the health burden of this disorder relative to the general population and to other chronic diseases has not been previously evaluated. One hundred fifty-eight patients with chronic sinusitis and no prior surgery underwent cross-sectional evaluation by use of the Medical Outcome Study Short-form 36-Item Health Survey. These patients were all referred for otolaryngologic care, and more than 80% subsequently underwent sinus surgery. Mean scores were compared from the eight subscales of general health assessment with similarly derived data for the United States general population. Significant differences (p < 0.05) were seen in several domains, including bodily pain, general health, vitality, and social functioning. Comparisons with other chronic diseases revealed significantly lower scores (p < 0.05) in measures of bodily pain and social functioning for sinusitis patients than in patients with congestive heart failure, angina, chronic obstructive pulmonary disease, and back pain. These findings suggest that the national health impact of chronic sinusitis is far greater than is currently appreciated.
Sealed vacuum electronic devices by surface micromachining (2002)

Solid-state planar micromachining techniques have been applied in the fabrication of two types of vacuum microelectronic devices. Cold-cathode devices based on field emission and hot-cathode devices based on thermal-field emission have been fabricated for possible use in high-speed, high-operating-temperature device applications. Polycrystalline silicon has been used as the cathode, anode, and gate material in these device structures. On-chip vacuum-sealed cavities have been formed through the micromachining of polycrystalline silicon microbridges. An elevated and sealed polycrystalline silicon emission filament has also been formed by surface micromachining techniques. The measured transconductance of the hot-cathode triode is 3.4 mu A/V. Device operation and measured current versus voltage characteristics are presented for these devices.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Simulation-based comparisons of Tahoe, Reno and SACK TCP (1996)

This paper uses simulations to explore the benefits of adding selective acknowledgments (SACK) and selective repeat to TCP. We compare Tahoe and Reno TCP, the two most common reference implementations for TCP, with two modified versions of Reno TCP. The first version is New-Reno TCP, a modified version of TCP without SACK that avoids some of Reno TCP's performance problems when multiple packets are dropped from a window of data. The second version is SACK TCP, a conservative extension of Reno TCP modified to use the SACK option being proposed in the Internet Engineering Task Force (IETF). We describe the congestion control algorithms in our simulated implementation of SACK TCP and show that while selective acknowledgments are not required to solve Reno TCP's performance problems when multiple packets are dropped, the absence of selective acknowledgments does impose limits to TCP's ultimate performance. In particular, we show that without selective acknowledgments, TCP implementations are constrained to either retransmit at most one dropped packet per round-trip time, or to retransmit packets that might have already been successfully delivered.
EGene: a configurable pipeline generation system for automated sequence analysis (2005)

Summary: EGene is a generic, flexible and modular pipeline generation system that makes pipeline construction a modular job. EGene allows for third-party programs to be used and integrated according to the needs of distinct projects and without any previous programming or formal language experience being required. EGene comes with CoEd, a visual tool to facilitate pipeline construction and documentation. A series of components to build pipelines for sequence processing is provided. Availability: http://www.lbm.fmvz.usp.br/egene/ Contact: alan@ime.usp.br; argruber@usp.br Supplementary information: http://www.lbm.fmvz.usp.br/egene/
P2Y 12 H2 Haplotype Is Associated With Peripheral Arterial Disease (2003)

These data point to a role of the H2 haplotype in atherosclerosis and raise the possibility of relative thienopyridine resistance in carriers of the P2Y12 H2 haplotype.
One dose of cyclosporine A is protective at initiation of folic acid-induced acute kidney injury in mice (2012)

A single dose of CsA, currently used for organ transplant, significantly protects mice from FA-induced AKI, presumably through inhibition of cell death, inflammatory reaction, interstitial cell infiltration and fibrosis. The protective effects have the potential to open a completely new line of investigation in the prevention and treatment of AKI.
Calcium binding proteins. Elucidating the contributions to calcium affinity from an analysis of species variants and peptide fragments (1990)

This paper describes the sequence homology of calcium-binding proteins belonging to the troponin C superfamily. Specifically, this similarity has been examined for 276 twelve-residue calcium-binding loops. It has been found that, in the calcium-binding loop, several residues appear invariant, regardless of the species of origin or the affinity of the protein. These residues are Asp at position 1 (+X of the coordinating position of the calcium), Asp or Asn at position 3 (+Y), Gly at position 6, Ile at position 8, and Glu at position 12 (-Z). It has also been found that conservation of certain residues can vary in similar sites in similar proteins. For example, position 3 (+Y) in site 3 of troponin C is always an Asn, whereas in calmodulin the residue is always Asp. This study also examined the calcium-binding affinities of peptide fragments comprising the loop, helix-loop, loop-helix, and helix-loop-helix. These were compared with larger enzymatic or chemically generated protein fragments in an effort to understand the various contributions to the calcium-binding affinity of a single-site versus a two-site domain as found in troponin C and calmodulin. Based on free energy differences, it was found that a 34-residue helix-loop-helix peptide represents about 60% of the binding affinity found in the intact protein. Cooperativity with a second calcium binding site accounted for the remaining 40% of the affinity.
Deep learning with COTS HPC systems (2013)

Scaling up deep learning algorithms has been shown to lead to increased performance in benchmark tasks and to enable discovery of complex high-level features. Recent efforts to train extremely large networks (with over 1 billion parameters) have relied on cloudlike computing infrastructure and thousands of CPU cores. In this paper, we present technical details and results from our own system based on Commodity Off-The-Shelf High Performance Computing (COTS HPC) technology: a cluster of GPU servers with Infiniband interconnects and MPI. Our system is able to train 1 billion parameter networks on just 3 machines in a couple of days, and we show that it can scale to networks with over 11 billion parameters using just 16 machines. As this infrastructure is much more easily marshaled by others, the approach enables much wider-spread research with extremely large neural networks. 1.
Optimization of cardiac cell seeding and distribution in 3D porous alginate scaffolds (2002)

Cardiac tissue engineering has evolved as a potential therapeutic approach to assist in cardiac regeneration. We have recently shown that tissue-engineered cardiac graft, constructed from cardiomyocytes seeded within an alginate scaffold, is capable of preventing the deterioration in cardiac function after myocardial infarction in rats. The present article addresses cell seeding within porous alginate scaffolds in an attempt to achieve 3D high-density cardiac constructs with a uniform cell distribution. Due to the hydrophilic nature of the alginate scaffold, its >90% porosity and interconnected pore structure, cell seeding onto the scaffold was efficient and short, up to 30 min. Application of a moderate centrifugal force during cell seeding resulted in a uniform cell distribution throughout the alginate scaffolds, consequently enabling the loading of a large number of cells onto the 3D scaffolds. The percent cell yield in the alginate scaffolds ranged between 60-90%, depending on cell density at seeding; it was 90% at seeding densities of up to 1 x 10(8) cells/cm(3) scaffold and decreased to 60% at higher densities. The highly dense cardiac constructs maintained high metabolic activity in culture. Scanning electron microscopy revealed that the cells aggregated within the scaffold pores. Some of the aggregates were contracting spontaneously within the matrix pores. Throughout the culture there was no indication of cardiomyocyte proliferation within the scaffolds, nor was it found in 3D cultures of cardiofibroblasts. This may enable the development of cardiac cocultures, without domination of cardiofibroblasts with time.
CHS 828, a novel pyridyl cyanoguanidine with potent antitumor activity in vitro and in vivo. (1999)

A new class of recently discovered antineoplastic agents, the pyridyl cyanoguanidines, exert a potent antitumor activity in rodents after oral administration. Optimization in vitro and in vivo has resulted in the selection of the lead candidate CHS 828 (N-(6-chlorophenoxyhexyl)-N'cyano-N"-4-pyridylguanidine). CHS 828 was found to exert potent cytotoxic effects in human breast and lung cancer cell lines, with lesser effects on normal fibroblasts and endothelial cells. In a study using a panel of cell lines with different resistance patterns, the effects of CHS 828 showed a low correlation with the activity patterns of known anticancer agents, and no sensitivity to known mechanisms of multidrug resistance was observed. In nude mice bearing human tumor xenografts, CHS 828, at doses from 20 to 50 mg/kg/day p.o., inhibited the growth of MCF-7 breast cancer tumors and caused regression of NYH small cell lung cancer tumors. Oral administration of CHS 828 once weekly improved efficacy without increasing toxicity. CHS 828 was found to compare favorably with established chemotherapeutic agents such as cyclophosphamide, etoposide, methotrexate, and paclitaxel. In mice with NYH tumors, long-term survival (>6 months) was observed after treatment with CHS 828 was stopped. In conclusion, CHS 828 is an effective new antitumor agent, with a potentially new mechanism of action. CHS 828 is presently being tested in Phase I clinical trials in collaboration with the European Organization for Research and Treatment of Cancer.