gebhart/patrepeval huggingface dataset:
Transcriptional switch by activating transcription factor 2-derived peptide sensitizes melanoma cells to apoptosis and inhibits their tumorigenicity (2004)

The notorious resistance of melanoma cells to drug treatment can be overcome by expression of a 50-aa peptide derived from activating transcription factor 2 (ATF2(50-100)). Here we demonstrate that ATF2(50-100) induced apoptosis by sequestering ATF2 to the cytoplasm, thereby inhibiting its transcriptional activities. Furthermore, ATF2(50-100) binds to c-Jun N-terminal kinase (JNK) and increases its activity. Mutation within ATF2(50-100) that impairs association with JNK and the inhibition of JNK or c-Jun expression by RNA interference (RNAi) reduces the degree of ATF2(50-100)-induced apoptosis. In contrast, TAM67, a dominant negative of the Jun family of transcription factors, or JunD RNAi attenuates sensitization of melanoma cells expressing ATF2(50-100) to apoptosis after treatment with anisomycin, which is used as a model drug. Mutations within the JNK binding region of ATF2(50-100) or expression of TAM67 or JunD RNAi attenuates inhibition of melanoma's tumorigenicity by ATF2(50-100). We conclude that inhibition of ATF2 in concert with increased JNK/Jun and JunD activities is central for the sensitization of melanoma cells to apoptosis and inhibition of their tumorigenicity.
New Insights into the Mechanism of Ruthenium-Catalyzed Olefin Metathesis Reactions (2001)

Over the past two decades, olefin metathesis has emerged as a mild and efficient method for the formation of carbon−carbon double bonds. In particular, (PCy_3)_2(Cl)_2RuCHPh (1)^2 has found extensive use in organic and polymer chemistry due to its high reactivity with olefins in the presence of a diverse array of functional groups. Recently, a new family of ruthenium-based olefin metathesis catalysts have been prepared by the substitution of a single PCy_3 ligand of 1 with an N-heterocyclic carbene. These new alkylidenes, particularly [Figure 1], exhibit dramatically increased activity over the parent system in ring-opening metathesis polymerization, ring-closing metathesis,4a and cross metathesis reactions. The mechanism of olefin metathesis reactions catalyzed by 1 has received intense investigation in our group and others and early studies established that phosphine dissociation is a crucial step along the reaction coordinate. As such, it has been suggested that the high activity of 2 and its analogues is due to their increased ability to promote this critical phosphine dissociation step. We report herein a detailed mechanistic study of phosphine exchange and initiation kinetics in alkylidenes 1 and 2. This study provides new and surprising evidence concerning the origin of the large activity differences between these two catalysts.
Molecular cloning and characterization of a novel type of regulatory protein (GDI) for smg p25A, a ras p21-like GTP-binding protein. (1990)

We recently purified to near homogeneity a novel type of regulatory protein for smg p25A, a ras p21-like GTP-binding protein, from bovine brain cytosol. This regulatory protein, named smg p25A GDP dissociation inhibitor (GDI), regulates the GDP-GTP exchange reaction of smg p25A by inhibiting dissociation of GDP from and subsequent binding of GTP to it. In the present studies, we isolated and sequenced the cDNA of smg p25A GDI from a bovine brain cDNA library by using an oligonucleotide probe designed from the partial amino acid sequence of purified smg p25A GDI. The cDNA has an open reading frame that encodes a protein of 447 amino acids with a calculated Mr of 50,565. This Mr is similar to those of the purified smg p25A GDI estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and sucrose density gradient ultracentrifugation, which are about 54,000 and 65,000, respectively. The isolated cDNA is expressed in Escherichia coli, and the encoded protein exhibits GDI activity. smg p25A GDI is hydrophilic overall, except for one hydrophobic region near the N terminus. smg p25A GDI shares low amino acid sequence homology with the Saccharomyces cerevisiae CDC25-encoded protein, which has been suggested to serve as a factor that regulates the GDP-GTP exchange reaction of the yeast RAS2-encoded protein, but not with the beta gamma subunits of GTP-binding proteins having an alpha beta gamma subunit structure, such as Gs and Gi. The smg p25A GDI mRNA was present in various tissues, including not only tissues in which smg p25A was detectable but also tissues in which it was not detectable. This fact has raised the possibility that smg p25A GDI interacts with another G protein in tissues in which smg p25A is absent.
Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. (1995)

Resting autoreactive T cells are present in the circulation of normal individuals without pathologic consequences. In autoimmune animal models, stimulation of these self-reactive T cells in the presence of costimulatory molecules B7-1 results in T cell-mediated autoimmune disease, whereas B7-2 stimulation generates regulatory autoreactive T cells that abrogate disease severity. Thus, reactivation in the brain of myelin-autoreactive T cells by antigen with costimulatory molecules may be a critical event in the pathophysiology of multiple sclerosis (MS), a putative autoimmune disease of central nervous system (CNS) myelin. We investigated the expression of cytokines and costimulatory molecules in a panel of 41 histologically characterized CNS specimens from 15 MS and 10 control cases using semiquantitative reverse transcriptase-polymerase chain reaction and immunocytochemistry. In four cases, vascular CNS infarcts with inflammation were compared with MS plaques from the same brain. We observed increased expression of B7-1 and interleukin (IL) 12p40 in acute MS plaques, particularly from early disease cases but not in inflammatory infarcts. B7-1 staining was localized predominantly to the lymphocytes in perivenular inflammatory cuffs but not the parenchyma. In contrast, B7-2 was expressed predominantly on macrophages both in MS lesions of varied time duration and in inflammatory infarcts. These findings indicate that an early event in the initiation of MS involves upregulation of B7-1 and IL-12, resulting in conditions that maximally stimulate T cell activation and induction of T helper 1-type immune responses.
Interpretation of Changes in Health-related Quality of Life (2003)

In most circumstances, the threshold of discrimination for changes in health-related quality of life for chronic diseases appears to be approximately half a SD.
An adaptive post-filtering technique based on the modified Yule-Walker filter (1999)

This paper presents an adaptive time-domain post-filtering technique based on the modified Yule-Walker filter. Conventionally, post-filtering is derived from an original LPC spectrum. In general, this time-domain technique produces unpredictable spectral tilt that is hard to control by the modified LPC synthesis, inverse and high pass filtering and causes unnecessary attenuation or amplification of some frequency components that introduces muffling in speech quality. This effect increases when voice coders are tandemed together. Another approach of designing a post-filter was developed by McAulay and Quatieri (1991) which can only be used in sinusoidal based speech coders. We have also developed another new time-domain post-filtering technique. This technique eliminates the problem of spectral tilt in the speech spectrum and can be applied to various speech coders. The new post-filter has a flat frequency response at the formant peaks of the speech spectrum. Instead of looking at the modified LPC synthesis, inverse, and high pass filtering in the conventional time-domain technique, we gather information about the poles of the LPC spectrum in the new technique. This post-filtering technique has been used in a 4 kb/s harmonic excitation linear predictive coder (HE-LPC) and a subjective listening tests have indicated that this technique outperforms the conventional one in both one and two tandem connections.
A plant‐produced influenza subunit vaccine protects ferrets against virus challenge (2008)

Plants can be used as a production vehicle for vaccine development against influenza. Domains of HA can generate protective immune responses in ferrets.
Duodenal and ileal calcium absorption in the rat and effects of vitamin D (1983)

An in situ ligated loop procedure was applied to dissect transmural calcium transport in the intestine into two components, a saturable and a nonsaturable process. The existence of two such processes was confirmed in the duodenum, but ileal calcium transport was devoid of the saturable component. There was a small saturable component in the upper jejunum. The level of CaBP, the vitamin D-dependent cytosolic calcium-binding protein (Mr, approximately or equal to 9,000), corresponded to the magnitude of the saturable component. No CaBP was detected in the ileum. Vitamin D dependence of the saturable component was established by inducing it in the duodenum of vitamin D-deficient animals following intraperitoneal injection of 1,25-dihydroxyvitamin D3. In these same animals, conversely, the ileum did not respond to exogenous 1,25-dihydroxyvitamin D3. This confirms the absence in the ileum of the saturable component of transmural calcium movement and the fact that the nonsaturable component is not vitamin D dependent. Everted sac experiments also showed that duodenal sacs from vitamin D-replete or -repleted animals transported calcium against a chemical gradient, whereas ileal sacs did not. Vitamin D regulation of intestinal calcium absorption thus occurs only in the proximal intestine, even though calcium is absorbed down its chemical gradient all along the small intestine.
Robertsonian translocations--reproductive risks and indications for preimplantation genetic diagnosis (2001)

For fertile couples, careful risk assessment and genetic counselling should precede consideration for PGD. Where translocation couples need assisted conception for subfertility, PGD is a valuable screen for imbalance, even when the risk of viable chromosome abnormality is low.
Oligolysine-based Oligosaccharide Clusters (2003)

Dendritic cells are potent antigen-presenting cells that express several membrane lectins, including the mannose receptor and DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin). To identify highly specific ligands for these dendritic cell receptors, oligosaccharides were converted into glycosynthons (Os1) and were used to prepare oligolysine-based glycoclusters, Os-[Lys(Os)]n-Ala-Cys-NH2. Clusters containing two to six dimannosides as well as clusters containing four or five pentasaccharides (Lewisa or Lewisx) or hexasaccharides (Lewisb) were synthesized. The thiol group of the appended cysteine residue allows easy tagging by a fluorescent probe or convenient substitution with an antigen. Surface plasmon resonance was used to determine the affinity of the different glycoclusters for purified mannose receptor and DC-SIGN, whereas flow cytometry and confocal microscopy analysis allowed assessment of cell uptake of fluoresceinyl-labeled glycoclusters. Dimannoside clusters are recognized by the mannose receptor with an affinity constant close to 106 liter.mol-1 but have a very low affinity for DC-SIGN (less than 104 liter x mol-1). Conversely, Lewis clusters have a higher affinity toward DC-SIGN than toward the mannose receptor. Dimannoside clusters are efficiently taken up by human dendritic cells as well as by rat fibroblasts expressing the mannose receptor but not by HeLa cells or rat fibroblasts expressing DC-SIGN; DC-SIGN-expressing cells take up Lewis clusters. The results suggest that ligands containing dimannoside clusters can be used specifically to target the mannose receptor, whereas ligands containing Lewis clusters will be targeted to DC-SIGN.
Live Oka/Merck Varicella Vaccine in Healthy Children (1985)

A clinical trial among 137 healthy children, ages 1 to 12 years, was conducted with four different doses (4,350, 870, 435, and 43 plaque-forming units [pfu]) of live Oka/Merck varicella vaccine to evaluate clinical reactions and selected laboratory parameters and to determine the minimum effective dose and induction time of antibody. The vaccine was well tolerated with no significant difference in the rate of reported symptoms by dose. The frequency of varicellalike rash was 3% (4/137); all rashes were mild. Serum aminotransferase values were essentially unchanged after vaccination. Minor variations found in platelet counts after vaccination were not associated with any bleeding, bruising, or clotting. Among initially seronegative children who received doses of 435 pfu or greater, 94% assayed at two weeks and 100% assayed at four or six weeks seroconverted. The geometric mean titers were similar for all four doses at six weeks. IgG and IgA responses were demonstrated with no relation to the vaccine dose.
Cystic fibrosis mutation detection by hybridization to light‐generated DNA probe arrays (1996)

We have combined photochemistry and photolithography with solid-phase DNA synthesis chemistry to form a new technology that makes high density oligonucleotide probe array synthesis possible. Hybridization to these two-dimensional arrays containing hundreds or thousands of oligonucleotide probes provides a powerful DNA sequence analysis tool. Two types of light-generated DNA probe arrays have been used to test for a variety of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. One array, made up of 428 probes, was designed to scan through the length of CFTR exon 11 and identify differences from the wild type reference sequence. The second type of array contained 1480 probes chosen to detect known deletions, insertions, or base substitution mutations. The validity of the probe arrays was established by hybridizing them with fluorescently labeled control oligonucleotide targets. Characterized mutant CFTR genomic DNA samples were then used to further test probe array hybridization specificity. Finally, ten unknown patient samples were genotyped using the CFTR probe array assay. The genotype assignments were identical to those obtained by PCR product restriction fragment analysis. Our results show that light-generated DNA probe arrays are highly effective in analyzing complex mutation and polymorphism patterns in a relatively large gene such as CFTR. © 1996 Wiley-Liss, Inc.
Comparison of Antibody Repertoires Produced by HIV-1 Infection, Other Chronic and Acute Infections, and Systemic Autoimmune Disease (2011)

The striking difference between the Abs produced during chronic vs. acute viral infection suggests that Abs bearing long CDR-H3s, high levels of SM and V(H)1-69 gene usage may be preferentially selected during persistent infection.
Novel Biomarkers for Predicting Preeclampsia (2008)

Preeclampsia is a major cause of maternal morbidity and mortality worldwide. Despite decades of research into the condition, the ability of clinicians to predict preeclampsia prior to the onset of symptoms has not improved significantly. In this review, we will examine the pathophysiology underlying preeclampsia and will look at potential biomarkers for early prediction and diagnosis. In addition, we will explore potential future areas of research into the condition.
Polymers with tunable toxicity: A reference scale for cytotoxicity testing of biomaterial surfaces (2007)

A series of copolymers, with varying ratio di-methylamino-ethylmethacrylate (DMAEMA) and methyl-methacrylate (MMA), was designed as a potential scale for cytotoxicity. These copolymers were characterized for toxicity of their surface. The surfaces of washed copolymers display increasing toxicity with increasing DMAEMA content. The toxicity was observed for three different cell-types, namely mouse fibroblasts, human endothelial cells and human osteoblast-like cells. With an increasing toxic surface, cell growth was inhibited as was indicated by the proliferation marker Ki-67. Staining for F-actin revealed that with increasing DMAEMA, cells adopted a more and more round morphology, resulting in decreased surface-contact area. Immuno-staining for phospho-tyrosine or vinculin demonstrated gradual loss of focal adhesions on increasingly toxic surfaces. Surprisingly loss of focal adhesions coincided with an increase in paxillin and vinculin protein, indicating cells try compensating for loss of adhesion. This series of copolymers may have potential as a cytotoxicity scale. They provoke cellular responses ranging from highly toxic to completely non-toxic, with some showing intermediate toxicity.
Long-term compatibility of intraocular lens implant materials. (1991)

This paper provides a general review of the long-term compatibility of intraocular lenses (IOLs), with specific reference to the compatibility of synthetic polymers used to fabricate IOLs. The first IOL was implanted in 1949. It was composed of polymethylmethacrylate (PMMA) and placed in the posterior chamber of the eye. In 1990, approximately 1.4 million IOLs were implanted in the U.S., nearly all composed of PMMA and nearly all implanted in the posterior chamber of the eye. However, many changes have taken place in the past 40 years to improve the compatibility of IOLs and to make cataract surgery and IOL implantation among the safest and most effective major surgical procedures.
Measurement of regional cerebral blood flow in cat brain using intracarotid 2H2O and 2H NMR imaging (1990)

Cerebral blood flow (CBF) was measured in cat brain in vivo at 2.7 T using 2H NMR to monitor the washout of deuterated saline injected into both carotid arteries via the lingual arteries. In anesthetized cats, global CBF varied directly with PaCO2 over a range of 20-50 mm Hg, and the corresponding global CBF values ranged from 25 to 125 ml.100 g-1.min-1. Regional CBF was measured in a 1-cm axial section of cat brain using intracarotid deuterated saline and gradient-echo 2H NMR imaging. Blood flow images with a maximum pixel resolution of 0.3 x 0.3 x 1.0 cm were generated from the deuterium signal washout at each pixel. Image derived values for CBF agreed well with other determinations, and decreased significantly with hypocapnia.
CRP-mediated activation of complement in vivo: assessment by measuring circulating complement-C-reactive protein complexes (1996)

The in vivo function of C-reactive protein (CRP) is unknown. Among the in vitro functions assigned to CRP is the ability to activate complement via the classical pathway. To date, there is no evidence supporting that CRP exerts this function in vivo. We here show a novel approach to assess CRP-mediated complement activation in vivo, which is based on the property that activated complement factors C3 and C4 fix to CRP during complement activation induced by this acute phase protein. We developed specific ELISAs for complexes between CRP and C4b, C4d, C3b, or C3d. We established that in vitro complement-CRP complexes were formed only during CRP-dependent activation, and not during activation by other activators, even in the presence of high CRP levels. Circulating levels of complement-CRP complexes were undetectable in normal donors, but significantly increased in nine patients following implantation of a renal allograft. Importantly, levels of complement-CRP complexes did not change in these patients upon a bolus infusion of mAb OKT3, which induces activation of the classical complement pathway, demonstrating in vivo that complement-CRP complexes are not formed during CRP-independent activation of complement, even when CRP is elevated. We conclude that measurement of complement-CRP complexes provides a suitable tool to study CRP-mediated activation of complement in vivo. Furthermore, increased levels of these complexes occur in clinical samples, indicating that CRP may induce activation of complement in vivo.
Risks and Benefits of Celecoxib to Prevent Recurrent Adenomas (2006)

In late September 2004, the cardiovascular risks identified in a placebo-controlled adenoma-prevention trial that was terminated early precipitated the voluntary withdrawal from the market of the cyclooxygenase-2 (COX-2) inhibitor rofecoxib.1 Later that year, in another adenoma-prevention trial, the COX-2 inhibitor, celecoxib, was also associated with an increase in the risk of cardiovascular events.2 For this reason, on December 17, 2004, the data and safety monitoring boards of two celecoxib trials recommended stopping drug administration in the trials.2,3 Articles describing the cardiovascular risks seen in the two adenoma prevention trials were published rapidly.1,4 However, in the absence of evidence . . .
Behavioral responses of streamer F mutants of Dictyostelium discoideum: Effects of cyclic GMP on cell motility (1992)

Streamer F (stmF) mutants have a prolonged increase in intracellular cGMP in response to addition of the chemoattractant cAMP. The speed of movement and area of stmF cells were quantitated as the cells were stimulated with a rapid, uniform increase in extracellular cAMP. The speed of stmF cells rapidly drops as does that of the wild-type, but then requires about 300 seconds to recover. In contrast, the speed of the parental strain, XP55, recovers within 60-70 seconds. This prolonged drop in speed correlates with the time during which intracellular cGMP remains high, suggesting that intracellular cGMP induces this prolonged reduction in speed. Mutants from other streamer complementation groups do not show this altered response. Area measurements indicate that stmF cells do not cringe or round up as XP55 does, but spread with the same kinetics as XP55. Chemotactic orientation of the stmF cells in stable spatial gradients is similar to or slightly greater than that of the wild-type. Tracking of cells moving during aggregation indicates that the stmF cells show large drops in speed between pulses, resulting in the banding pattern seen in streams. The cells can still respond to new pulses, resulting in an aggregation time that is similar to that of XP55.
Molecular Determinants of the Caspase-promoting Activity of Smac/DIABLO and Its Role in the Death Receptor Pathway (2000)

Smac/DIABLO is a mitochondrial protein that is released along with cytochrome c during apoptosis and promotes cytochrome c-dependent caspase activation by neutralizing inhibitor of apoptosis proteins (IAPs). We provide evidence that Smac/DIABLO functions at the levels of both the Apaf-1-caspase-9 apoptosome and effector caspases. The N terminus of Smac/DIABLO is absolutely required for its ability to interact with the baculovirus IAP repeat (BIR3) of XIAP and to promote cytochrome c-dependent caspase activation. However, it is less critical for its ability to interact with BIR1/BIR2 of XIAP and to promote the activity of the effector caspases. Consistent with the ability of Smac/DIABLO to function at the level of the effector caspases, expression of a cytosolic Smac/DIABLO in Type II cells allowed TRAIL to bypass Bcl-xL inhibition of death receptor-induced apoptosis. Combined, these data suggest that Smac/DIABLO plays a critical role in neutralizing IAP inhibition of the effector caspases in the death receptor pathway of Type II cells.