gebhart/patrepeval huggingface dataset:
Relaxin Family Peptides and Their Receptors (2013)

There are seven relaxin family peptides that are all structurally related to insulin. Relaxin has many roles in female and male reproduction, as a neuropeptide in the central nervous system, as a vasodilator and cardiac stimulant in the cardiovascular system, and as an antifibrotic agent. Insulin-like peptide-3 (INSL3) has clearly defined specialist roles in male and female reproduction, relaxin-3 is primarily a neuropeptide involved in stress and metabolic control, and INSL5 is widely distributed particularly in the gastrointestinal tract. Although they are structurally related to insulin, the relaxin family peptides produce their physiological effects by activating a group of four G protein-coupled receptors (GPCRs), relaxin family peptide receptors 1-4 (RXFP1-4). Relaxin and INSL3 are the cognate ligands for RXFP1 and RXFP2, respectively, that are leucine-rich repeat containing GPCRs. RXFP1 activates a wide spectrum of signaling pathways to generate second messengers that include cAMP and nitric oxide, whereas RXFP2 activates a subset of these pathways. Relaxin-3 and INSL5 are the cognate ligands for RXFP3 and RXFP4 that are closely related to small peptide receptors that when activated inhibit cAMP production and activate MAP kinases. Although there are still many unanswered questions regarding the mode of action of relaxin family peptides, it is clear that they have important physiological roles that could be exploited for therapeutic benefit.
The relationship between ventricular electrical delay and left ventricular remodelling with cardiac resynchronization therapy (2011)

Electrical dyssynchrony, as measured by QLV, was strongly and independently associated with reverse remodelling and QOL with CRT. Acute measurements of QLV may be useful to guide LV lead placement.
Comprehensive Analysis of the Factors Contributing to the Stability and Solubility of Autonomous Human VH Domains (2007)

We report a comprehensive analysis of sequence features that allow for the production of autonomous human heavy chain variable (V(H)) domains that are stable and soluble in the absence of a light chain partner. Using combinatorial phage-displayed libraries and conventional biophysical methods, we analyzed the entire former light chain interface and the third complementarity determining region (CDR3). Unlike the monomeric variable domains of camelid heavy chain antibodies (V(H)H domains), in which autonomous behavior depends on interactions between the hydrophobic former light chain interface and CDR3, we find that the stability of many in vitro evolved V(H) domains is essentially independent of the CDR3 sequence and instead derives from mutations that increase the hydrophilicity of the former light chain interface by replacing exposed hydrophobic residues with structurally compatible hydrophilic substitutions. The engineered domains can be expressed recombinantly at high yield, are predominantly monomeric at high concentrations, unfold reversibly, and are even more thermostable than typical camelid V(H)H domains. Many of the stabilizing mutations are rare in natural V(H) and V(H)H domains and thus could not be predicted by studying natural sequences and structures. The results demonstrate that autonomous V(H) domains with structural properties beyond the scope of natural frameworks can be derived by using non-natural mutations, which differ from those found in camelid V(H)H domains. These findings should enable the development of libraries of synthetic V(H) domains with CDR3 diversities unconstrained by structural demands.
Metastasis and AKT activation (2008)

Metastasis is responsible for 90% of cancer patient deaths. More information is needed about the molecular basis for its potential detection and treatment. The activated AKT kinase is necessary for many events of the metastatic pathway including escape of cells from the tumor's environment, into and then out of the circulation, activation of proliferation, blockage of apoptosis, and activation of angiogenesis. A series of steps leading to metastatic properties can be initiated upon activation of AKT by phosphorylation on Ser-473. These findings lead to the question of how this activation is connected to metastasis. Activated AKT phosphorylates GSK-3beta causing its proteolytic removal. This increases stability of the negative transcription factor SNAIL, thereby decreasing transcription of the transmembrane protein E-cadherin that forms adhesions between adjacent cells, thereby permitting their detachment. How is AKT hyperactivated in metastatic cells? Increased PI3K or TORC2 kinase activity- or decreased PHLPP phosphatase could be responsible. Furthermore, a positive feedback mechanism is that the decrease of E-cadherin lowers PTEN and thereby increases PIP3, further activating AKT and metastasis.
Innate Immunity to Adenovirus (2014)

Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and self-limiting in immunocompetent individuals. Here we describe how adenoviruses are recognized by the host innate defense system during entry and replication in immune and nonimmune cells. Innate defense protects the host and represents a major barrier to using adenoviruses as therapeutic interventions in humans. Innate response against adenoviruses involves intrinsic factors present at constant levels, and innate factors mounted by the host cell upon viral challenge. These factors exert antiviral effects by directly binding to viruses or viral components, or shield the virus, for example, soluble factors, such as blood clotting components, the complement system, preexisting immunoglobulins, or defensins. In addition, Toll-like receptors and lectins in the plasma membrane and endosomes are intrinsic factors against adenoviruses. Important innate factors restricting adenovirus in the cytosol are tripartite motif-containing proteins, nucleotide-binding oligomerization domain-like inflammatory receptors, and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 and cyclic guanosine monophosphate-adenosine monophosphate synthase. Adenovirus tunes the function of antiviral autophagy, and counters innate defense by virtue of its early proteins E1A, E1B, E3, and E4 and two virus-associated noncoding RNAs VA-I and VA-II. We conclude by discussing strategies to engineer adenovirus vectors with attenuated innate responses and enhanced delivery features.
Storage Resource Broker Global Data Grids (2006)

Abstract 1 International collaborations now manage globally distributed data collections based on the data and trust virtualization mechanisms provided by the Storage Resource Broker data grid. We examine the key requirements that have emerged from four production environments and illustrate how the desired capabilities have been implemented in the SRB. 1. Introduction. Globally distributed data reside in a complex heterogeneous environment characterized by multiple institutions, multiple administrative domains, multiple types of storage systems,
Increased Expression of Dihydrodiol Dehydrogenase Induces Resistance to Cisplatin in Human Ovarian Carcinoma Cells (2002)

We employed cDNA microarrays to identify the differentially expressed genes in a cisplatin-sensitive parental (2008) human ovarian carcinoma cell line and its cisplatin-resistant variant (2008/C13*). Differential expression of five genes was found in the 2008/C13* cells, a result confirmed by semi-quantitative reverse transcription-PCR. The five genes were identified as fibroblast muscle-type tropomyosin and skeletal muscle-type tropomyosin, dihydrodiol dehydrogenase, apolipoprotein J and glucose-6-phosphate dehydrogenase variant-A. Treatment of the 2008 cells with cisplatin (at its IC(50) concentration of 2 microm) induced expression of these genes, as determined by semi-quantitative reverse transcription-PCR analysis using gene-specific primers. In contrast, treatment of the drug-resistant 2008/C13* cells with cisplatin (at its IC(50) concentration of 20 microm) did not lead to the induction of any of the aforementioned genes. Most importantly, constitutive overexpression of dihydrodiol dehydrogenase (but not the other genes) in the 2008 cells led to induction of cisplatin resistance, clearly indicating its role in the development of the resistance phenotype in the 2008/C13* cells. The development of cisplatin resistance in the transfected cells was associated with an increase in the dihydrodiol dehydrogenase enzyme activity. Although at present it is not clear how dihydrodiol dehydrogenase is involved in cisplatin resistance, the identification of this gene as a causal factor suggests the existence of a hitherto undefined pathway resulting in cisplatin resistance.
Hydroboration of Unsaturated Phosphonic Esters:  Synthesis of Boronophosphonates and Trisubstituted Vinylphosphonates (2001)

[figure: see text] Hydroboration of vinyl phosphonates with pinacolborane (PBH) proceeds to give phosphonoboronates, 2. Surprisingly, such compounds have not been reported before. The reaction works well with terminal alkenylphosphonates. Internal alkenylphosphonates give complex mixtures. Hydroboration/Suzuki coupling of alkynylphosphonates, with PBH, in a one-pot procedure gives trisubstituted vinylphosphonates in good overall yields and provides a new synthesis of these compounds.
Ionizing radiation stimulates unidentified tyrosine-specific protein kinases in human B-lymphocyte precursors, triggering apoptosis and clonogenic cell death. (1992)

Very little is known regarding the effects of ionizing radiation on cytoplasmic signal transduction pathways. Here, we show that ionizing radiation induces enhanced tyrosine phosphorylation of multiple substrates in human B-lymphocyte precursors. This response to ionizing radiation was also observed in cells pretreated with vanadate, a potent protein-tyrosine-phosphatase (PTPase) inhibitor, and phosphotyrosyl [Val5]angiotensin II phosphatase assays showed no decreased PTPase activity in irradiated cells. Thus, enhanced tyrosine phosphorylation in irradiated B-lymphocyte precursors is not triggered by inhibition of total cellular PTPase activity. Immune-complex kinase assays using anti-phosphotyrosine antibodies demonstrated enhanced protein-tyrosine kinase (PTK) activity in the immunoprecipitates from irradiated cells, and the PTK inhibitors genistein and herbimycin effectively prevented radiation-induced tyrosine phosphorylation. Immune-complex kinase assays on irradiated and unirradiated B-lymphocyte precursors using antibodies prepared against unique amino acid sequences of p59fyn, p56/p53lyn, p55blk, and p56lck demonstrated that these Src-family tyrosine kinases were not the primary PTKs responsible for enhanced tyrosine kinase activity in the anti-phosphotyrosine antibody immunoprecipitates or for enhanced tyrosine phosphorylation of multiple substrates. Thus, our findings favor the hypothesis that ionizing radiation induces enhanced tyrosine phosphorylation in B-lymphocyte precursors by stimulation of as yet unidentified PTKs. Tyrosine phosphorylation appears to be an important proximal step in radiation-induced apoptosis and clonogenic cell death because inhibition of PTK prevents DNA fragmentation and loss of clonogenicity of irradiated B-lymphocyte precursors. Since PTKs play myriad roles in the regulation of cell function and proliferation, the activation of a PTK cascade, as detailed in this report, may explain some of the pleiotropic effects of ionizing radiation on cellular functions of B-lymphocytes and their precursors.
TGFβ alters growth and differentiation related gene expression in proliferating osteoblasts in vitro, preventing development of the mature bone phenotype (1994)

This study examines the mechanism by which TGF-beta 1, an important mediator of cell growth and differentiation, blocks the differentiation of normal rat diploid fetal osteoblasts in vitro. We have established that the inability for pre-osteoblasts to differentiate is associated with changes in the expression of cell growth, matrix forming, and bone related genes. These include histone, jun B, c-fos, collagen, fibronectin, osteocalcin, alkaline phosphatase, and osteopontin. Morphologically, the TGF-beta 1-treated osteoblasts exhibit an elongated, spread shape as opposed to the characteristic cuboidal appearance during the early stages of growth. This is followed by a decrease in the number of bone nodules formed and the amount of calcium deposition. These effects on differentiation can occur without dramatic changes in cell growth if TGF-beta 1 is given for a short time early in the proliferative phase. However, continuous exposure to TGF-beta 1 leads to a bifunctional growth response from a negative effect during the proliferative phase to a positive growth effect during the later matrix maturation and mineralization phases of the osteoblast developmental sequence. Extracellular matrix genes, fibronectin, osteopontin and alpha 1(I) collagen, are altered in their expression pattern which may provide an aberrant matrix environment for mineralization and osteoblast maturation and potentiate the TGF-beta 1 response throughout the course of osteoblast differentiation. The initiation of a TGF-beta 1 effect on cell growth and differentiation is restricted to the proliferative phase of the culture before the cells express the mature osteoblastic phenotype. Second passage cells that are accelerated to differentiate by the addition of dexamethasone or by seeding cultures at a high density are refractory to TGF-beta 1. These in vitro results indicate that TGF-beta 1 exerts irreversible effects at a specific stage of osteoblast phenotype development resulting in a potent inhibition of osteoblast differentiation at concentrations from 0.1 ng/ml.
A Human Leucocyte Antigen‐DR1 Transgene Confers Susceptibility to Experimental Allergic Encephalomyelitis Elicited by an Epitope of Myelin Basic Protein (2003)

Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA-restricted presentation of T-cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of myelin epitopes presented by HLA class II molecules in experimental model of multiple sclerosis (experimental allergic encephalomyelitis (EAE)). As a first step towards humanized disease models in HLA Tg mice, we have analysed immune response of lymph node cells of HLA-DR1 Tg mice immunized with the human myelin basic protein (MBP) peptides 13-33, 87-106 and 139-154 bound by HLA-DR1. We report here that HLA-DR1 Tg mice display a hierarchy of response in vivo and in vitro to MBP epitopes depending on the binding affinity to DRB*0101 molecule. In fact, the 13-33 epitope induced a strong T helper 1 (Th1) response accompanied by high T-cell precursor frequency and caused mild EAE, while the two other epitopes gave poor (139-154) or no disease (87-106), and these data correlate with in vitro Th1 response. These data could prove a useful tool in understanding the role played by different MBP epitopes in EAE.
Purification and Characterization of 3'-Phosphoadenosine-5'-Phosphosulfate: GalCer Sulfotransferase from Human Renal Cancer Cells (1996)

We have purified 3'-phosphoadenosine-5'-phosphosulfate:GalCer sulfotransferase [EC 2.8.2.11] from a human renal cancer cell line SMKT-R3 through a combination of affinity chromatographies using galactosylsphingosine, 3',5'-bisphosphoadenosine and heparin as ligands. The purified sulfotransferase showed a specific activity of 1.2 mumol/min/mg, which is 300 times more than the highest activity among the enzyme preparations purified so far from other sources. Homogeneity of the purified sulfotransferase was supported by the facts that the enzyme preparation showed a single protein band with an apparent molecular mass of 54 kDa on reducing SDS-PAGE and that protein bands coincided with the enzyme activity on both native PAGE and nonreducing SDS-PAGE. GalCer was the best acceptor for the purified enzyme. LacCer, GalAAG, and GalDG were also good acceptors. GlcCer, Gg3Cer, Gg4Cer, Gb4Cer, and nLc4Cer did serve as acceptors although the relative activities were low. On the other hand, the enzyme could not act on Gb3Cer, which possesses alpha-galactoside at the nonreducing terminus. Neither galactose nor lactose served as an acceptor. These observations suggest that the sulfotransferase prefers beta-glycoside, especially beta-galactoside, at the nonreducing termini of sugar chains attached to a lipid moiety.
Image-based visual hulls (2000)

In this paper, we describe an efficient image-based approach to computing and shading visual hulls from silhouette image data. Our algorithm takes advantage of epipolar geometry and incremental computation to achieve a constant rendering cost per rendered pixel. It does not suffer from the computation complexity, limited resolution, or quantization artifacts of previous volumetric approaches. We demonstrate the use of this algorithm in a real-time virtualized reality application running off a small number of video streams.
Early cleavage of human embryos to the two-cell stage after intracytoplasmic sperm injection as an indicator of embryo viability (1998)

In-vitro fertilization (IVF) embryos are selected for transfer on the basis of morphology and rate of development. However, when a number of embryos have similar characteristics, the selection of the best embryos is left to chance. Recently, we proposed a simple, novel method to overcome this problem, based on pre-selection of embryos cleaving early to the two-cell stage. In this study we have adopted the same method to choose embryos fertilized after intracytoplasmic sperm injection (ICSI). Fertilized embryos that had cleaved to the two-cell stage by 27 h post-injection were designated as 'early cleavage' embryos, while those that had not yet reached the two-cell stage were designated as 'no early cleavage'. In all cases, the early cleavage embryos were transferred when available. Early cleavage was observed in 54 (61.4%) of the 88 cycles assessed. There were significantly (P = 0.04) more clinical pregnancies in the early cleavage group, 14/54 (25.9%), compared with the no early cleavage group 2/34 (3.2%). No differences between the groups were found when comparing key parameters (age, stimulation protocol and semen characteristics) of the couples. Using the ICSI technique, we have shown that early cleavage to the two-cell stage is not influenced by the timing of fertilization, and is more likely due to intrinsic factors within the oocyte or embryo that promote embryo cleavage after fertilization.
Methodology for trench capacitor etch optimization using voltage contrast inspection and special processing (2010)

Embedded DRAM will play a much larger part in IBM server microprocessors for new SOI technologies. Etch of a deep trench (DT) into the substrate, which is used to form the capacitor, is a complicated multi-step process. One of the key elements is etch of the buried oxide layer. Voltage contrast (VC) inspection is used to detect defective DTs and can differentiate between opens in the buried oxide and those in the oxide hard mask. So these defects have a VC signal, special processing is needed to seal off the SOI layer. The process of finding the right beam conditions to detect the opens in the buried oxide, which are very subtle, is described. Failure analysis of these defects is also presented.
The fractional maximal effect method: a new way to characterize the effect of antibiotic combinations and other nonlinear pharmacodynamic interactions (1993)

The checkerboard technique leading to the fractional inhibitory concentration indexes and the killing curve method are currently the most widely used methods to study antibiotic combinations. For both methods, experimental conditions and interpretation criteria are somewhat arbitrary. The relevance of the fractional inhibitory concentration index computation, in the classic case of additivity [P = d1/(D1)p + d2/(D2)p, where d1 and d2 are the doses of drugs 1 and 2 in combination to produce an effect at a percent level (P) and (D1)p and (D2)p are the doses required for the two respective drugs alone to produce the same effect] relies on the assumption of a linear relationship between the MIC and the concentration of the test antibiotics. In addition, there is no consensus as to the definition of synergy in killing curve interpretation. The fractional maximal effect (FME) method is a new approach which was developed to handle the nonlinear pharmacodynamics exhibited by antibiotics and other drugs. This method relies on the mathematical linearization of the nonlinear concentration-effect scales and eventual construction of an isobologram-type data plot. The FME method was applied to study interactions between several antibiotic combinations: amoxicillin and tetracycline, ciprofloxacin and erythromycin, and ticarcillin and tobramycin. These combinations were selected because the pharmacologic basis for their interactions has been previously described. The FME method correctly identified antagonism for the first two combinations and synergism for the last combination. Conclusions were reproducible across the range of concentrations studied. Besides providing information on the nature of the interaction, the method can rapidly explore the effect of changing concentration ratios of two antimicrobial agents on the degrees of interaction. The FME method may be applied to interactions between drugs or agents with either a linear or nonlinear endpoint measurement. Methods frequently used for drug combination testing are also discussed in the paper.
Four-valued interface circuits for NMOS VLSI (1987)

Abstract In this paper we present radix 4 to binary encoder and decoder interface circuits for NMOS VLSI. The circuits can be implemented using standard binary NMOS fabrication processes and are designed to operate correctly over the entire target range of device parameters specified by MOSIS. They have been simulated using SPICE with the typical parameters provided by MOSIS, and found to work correctly. Thus these circuits can be readily used to reduce pinouts of binary NMOS logic chips, and thereby allow significant cost savings.
C-Reactive Protein and Other Markers of Inflammation in the Prediction of Cardiovascular Disease in Women (2000)

The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events.
Commonly asked questions about nightguard vital bleaching. (1994)

There are three basic classes of materials and techniques used for the bleaching of vital teeth. These include the in-office bleaching technique with 35 percent hydrogen peroxide, the Nightguard vital bleaching technique with 10 percent carbamide peroxide, and the over-the-counter bleaching kits with three-to-six percent hydrogen peroxide. The most popular of these techniques is Nightguard vital bleaching, also referred to as dentist-prescribed, home-applied bleaching. This article looks at the current status of the Nightguard vital bleaching technique, with a special emphasis on the clinical aspects of the treatment, along with the most commonly asked questions concerning the procedure. It would still appear than this form of dentist-prescribed, home-applied bleaching, when preceded by a proper examination and correct diagnosis, applied with a properly fitted prosthesis, and monitored as needed by a dentist, is as safe as other accepted dental procedures or commonly ingested foodstuffs.