gebhart/patrepeval huggingface dataset:
Inhibition of Factor IX(a) Is Protective in a Rat Model of Thromboembolic Stroke (2002)

The data indicate that the inhibition of factor IX(a) within 4 hours of thromboembolic stroke produced a more favorable outcome than tPA. When treatment was initiated 6 hours after stroke, the benefits of factor IX(a) inhibition were lost, whereas tPA continued to suppress lesion development, albeit without a corresponding improvement in functional deficits. This study suggests that cerebral ischemia and the resultant perfusion deficit are exacerbated by the activation of blood coagulation and that anticoagulants like SB 249417 may find utility in the treatment of ischemic stroke.
A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements (2004)

We report a method for studying global DNA methylation based on using bisulfite treatment of DNA and simultaneous PCR of multiple DNA repetitive elements, such as Alu elements and long interspersed nucleotide elements (LINE). The PCR product, which represents a pool of approximately 15 000 genomic loci, could be used for direct sequencing, selective restriction digestion or pyrosequencing, in order to quantitate DNA methylation. By restriction digestion or pyrosequencing, the assay was reproducible with a standard deviation of only 2% between assays. Using this method we found that almost two-thirds of the CpG methylation sites in Alu elements are mutated, but of the remaining methylation target sites, 87% were methylated. Due to the heavy methylation of repetitive elements, this assay was especially useful in detecting decreases in DNA methylation, and this assay was validated by examining cell lines treated with the methylation inhibitor 5-aza-2'deoxycytidine (DAC), where we found a 1-16% decrease in Alu element and 18-60% LINE methylation within 3 days of treatment. This method can be used as a surrogate marker of genome-wide methylation changes. In addition, it is less labor intensive and requires less DNA than previous methods of assessing global DNA methylation.
Association of CD22 with the B cell antigen receptor (1993)

The antigen receptor on B lymphocytes is composed of membrane immunoglobulin sheathed by an alpha/beta heterodimer. This structure is in several respects analogous to the antigen receptor on T cells except that, in the case of the T cell but not the B cell receptor, several receptor-associated proteins have been described which may modulate the effects of antigen interaction (e.g. CD4, CD8, CD2 and CD5). To screen for specific associations with the B cell antigen receptor that might be of only low stoichiometry, we have exploited the sensitivity of in vitro kinase assays. We show that the B cell antigen receptor associates with CD22. The association is specific and stable, but Western blotting reveals it to be of low stoichiometry (0.2 to 2% of membrane immunoglobulin is CD22 associated). The CD22/antigen receptor association was demonstrated with multiple isotypes (IgM, IgD and IgG) and was evident both in Burkitt lymphoma lines and in tonsil cells. Whilst the significance of the association is unknown, it is notable that CD22 is a B cell-specific adhesion molecule which we find contains within its cytoplasmic domain a sequence bearing high homology to the "Reth motif" implicated in signal transduction. Indeed, CD22 becomes tyrosine phosphorylated less than one minute after antigen-receptor cross-linking. Thus, it is tempting to speculate that interactions involving CD22 assist in the antigen-mediated triggering of B cell activation.
A New DNA Minor Groove Binding Motif: Cross-Linked Lexitropsins (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA New DNA Minor Groove Binding Motif: Cross-Linked LexitropsinsYong-Huang Chen and J. William LownCite this: J. Am. Chem. Soc. 1994, 116, 16, 6995–7005Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/ja00095a001https://doi.org/10.1021/ja00095a001research-articleACS PublicationsRequest reuse permissionsArticle Views318Altmetric-Citations50LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A Human Novel Gene DERPC Located on 16q22.1 Inhibits Prostate Tumor Cell Growth and Its Expression Is Decreased in Prostate and Renal Tumors (2002)

This study suggests that decreased expression of DERPC may be implicated in tumorigenesis of renal and CaPs.
Helical structure determined by NMR of the HIV‐1 (345–392)Gag sequence, surrounding p2: Implications for particle assembly and RNA packaging (2005)

Gag protein oligomerization, an essential step during virus assembly, results in budding of spherical virus particles. This process is critically dependent on the spacer p2, located between the capsid and the nucleocapsid proteins. P2 contributes also, in association with NCp7, to specific recognition of the HIV-1 packaging signal resulting in viral genome encapsidation. There is no structural information about the 20 last amino acids of the C-terminal part of capsid (CA[CTD]) and p2, in the molecular mechanism of Gag assembly. In this study the structure of a peptide encompassing the 14 residues of p2 with the upstream 21 residues and the downstream 13 residues was determined by (1)H NMR in 30% trifluoroethanol (TFE). The main structural motif is a well-defined amphipathic alpha-helix including p2, the seven last residues of the CA(CTD), and the two first residues of NCp7. Peptides containing the p2 domain have a strong tendency to aggregate in solution, as shown by gel filtration analyses in pure H(2)O. To take into account the aggregation phenomena, models of dimer and trimer formed through hydrophobic or hydrophilic interfaces were constructed by molecular dynamic simulations. Gel shift experiments demonstrate that the presence of at least p2 and the 13 first residues of NCp7 is required for RNA binding. A computer-generated model of the Gag polyprotein segment (282-434)Gag interacting with the packaging element SL3 is proposed, illustrating the importance of p2 and NCp7 in genomic encapsidation.
Effect of antibodies on chemiluminescence and on killing of Streptococcus sobrinus by polymorphonuclear leukocytes (1996)

The effect of a polyclonal antiserum and OMVU10, a monoclonal antibody reactive with Antigen B of Streptococcus sobrinus, on the interaction of polymorphonuclear leukocytes with S. sobrinus was studied, using chemiluminescence and bacterial killing assays. Increased stimulation of neutrophils as measured in the chemiluminescence assays was established when S. sobrinus was preincubated with polyclonal antiserum or when polyclonal antiserum was added to the reaction mixture. Higher counts were measured in comparison to preimmune serum. After 90 min, 52% of S. sobrinus preincubated with polyclonal antiserum was killed. Killing was also increased when polyclonal antiserum was added to the reaction mixture in comparison to the controls. No killing was found when bacteria were preincubated with OMVU10 or when OMVU10 was added to the reaction mixture in comparison to Clone 24, a control antibody.
CD4+ T-cell immunity to mutated ras protein in pancreatic and colon cancer patients. (1995)

Mutated p21 ras proteins contain single substituted amino acid residues and represent cancer-specific proteins. The current study examined whether primed T cell immunity to mutant p21 ras proteins and/or peptides can be detected in patients with pancreatic or colon cancer. Studies focused on the aspartic acid substitution in amino acid position 12 (denoted D12) as the commonest mutation in gastrointestinal malignancy. Peripheral blood lymphocytes from patients or normal individuals were tested for the ability to proliferate in response to normal or mutated ras peptides or proteins. T-cell responses were defined as a stimulation index of > 2.0. Results showed that 7 of 16 (44%) pancreatic cancer patients responded to ras-D12 peptide. Responses to ras-D12 protein were studied in only the last four patients that responded to D12 peptides. Three of the 4 patients that responded to ras-D12 peptide showed a substantial response to p21 ras-D12 protein (stimulation indices of 12, 8, and 24). Specificity was validated by examining responses to normal and alternate ras peptides and proteins. T-cell responses to ras-D12 peptides were detected in only 2 of 25 (8%) colon cancer patients. None of 11 normal individuals tested had positive responses to normal or mutant ras p21 proteins and/or peptides. Thus, CD4+ T-cell immunity to the mutated segment of ras protein is present in some patients with gastrointestinal cancer.
Crucial role of metal surface in enhanced transmission through subwavelength apertures (2000)

In order to understand the details of the extraordinary enhancement of the optical transmission through subwavelength holes in metal films, we have fabricated perforated free-standing metal films where the nature of the bulk and surfaces can be controlled independently. We find that the transmission enhancement depends only on the dielectric properties of the metal within a skin depth of the two in-plane surfaces and not on those of the film core, nor on the metal constituting the hole walls. This provides direct and conclusive evidence that the phenomenon is mediated by surface plasmons.
Cutaneous manifestation of neurofibromatosis: cellular interaction, pigmentation, and mast cells. (1981)

The patchy, mosaic nature of the hyperpigmentation defect in neurofibromatosis (NF) is shown to be compatible with a cell-cell interaction model involving at least 2, and perhaps 3 cell types. Two approaches to analysis of the cellular interaction model are outlined in detail: 1) Demonstration of the more or less random number, size, and distribution of café-au-lait spots (CLS); 2) Documentation of topographic features of hyperpigmentation and neurofibroma skin lesions with special significance, including: a) Localized, intense pruritus coincident with developing or numerous neurofibromas, responding to treatment with antihistamines or oral disodium cromoglycate (the mast cell is suggested as a mediator of the pruritus and perhaps of neurofibroma development); b) The high frequency of areolar neurofibromas in postpubertal NF females, suggesting a localized estrogenic effect on neurofibroma development; c) The recognition that the usual NF freckling (eg axillary) is essentially restricted to intertriginous zones and that they therefore probably have a different mechanism of origin than do CLS.
A Bright and Fast Red Fluorescent Protein Voltage Indicator That Reports Neuronal Activity in Organotypic Brain Slices (2016)

Optical imaging of voltage indicators based on green fluorescent proteins (FPs) or archaerhodopsin has emerged as a powerful approach for detecting the activity of many individual neurons with high spatial and temporal resolution. Relative to green FP-based voltage indicators, a bright red-shifted FP-based voltage indicator has the intrinsic advantages of lower phototoxicity, lower autofluorescent background, and compatibility with blue-light-excitable channelrhodopsins. Here, we report a bright red fluorescent voltage indicator (fluorescent indicator for voltage imaging red; FlicR1) with properties that are comparable to the best available green indicators. To develop FlicR1, we used directed protein evolution and rational engineering to screen libraries of thousands of variants. FlicR1 faithfully reports single action potentials (∼3% ΔF/F) and tracks electrically driven voltage oscillations at 100 Hz in dissociated Sprague Dawley rat hippocampal neurons in single trial recordings. Furthermore, FlicR1 can be easily imaged with wide-field fluorescence microscopy. We demonstrate that FlicR1 can be used in conjunction with a blue-shifted channelrhodopsin for all-optical electrophysiology, although blue light photoactivation of the FlicR1 chromophore presents a challenge for applications that require spatially overlapping yellow and blue excitation.
Noninvasive, In Utero Imaging of Mouse Embryonic Heart Development With 40-MHz Echocardiography (1998)

We used 40-MHz echocardiography to identify key elements of the early mouse embryonic cardiovascular system and for noninvasive dimensional analysis of developing cardiac ventricles. The ability to perform serial measurements and to detect mutant embryos with cardiac defects highlights the usefulness of the technique for investigating normal and abnormal cardiovascular development.
Enteric β-Defensin: Molecular Cloning and Characterization of a Gene with Inducible Intestinal Epithelial Cell Expression Associated with Cryptosporidium parvum Infection (1998)

A growing body of evidence suggests that endogenous antibiotics contribute to the innate defense of mammalian mucosal surfaces. In the cow, beta-defensins constitute a large family of antibiotic peptides whose members have been previously isolated from the respiratory and oral mucosa, as well as circulating phagocytic cells. A novel bovine genomic clone with beta-defensin-related sequence [corrected] related to those of these alpha-defensins was isolated and characterized. The corresponding cDNA was isolated from a small intestinal library; its open reading frame predicts a deduced sequence of a novel beta-defensin, which we designate enteric beta-defensin (EBD). Northern blot analysis of a variety of bovine tissues revealed that EBD mRNA is highly expressed in the distal small intestine and colon, anatomic locations distinct from those for previously characterized beta-defensins. EBD mRNA was further localized by in situ hybridization to epithelial cells of the colon and small intestinal crypts. Infection of two calves with the intestinal parasite Cryptosporidium parvum induced 5- and 10-fold increases above control levels of EBD mRNA in intestinal tissues. An anchored-PCR strategy was used to identify other beta-defensin mRNAs expressed in the intestine. In addition to that of EBD, several low-abundance cDNAs which corresponded to other beta-defensin mRNAs were cloned. Most of these clones encoded previously characterized beta-defensins or closely related isoforms, but two encoded a previously uncharacterized prepro-beta-defensin. Northern blot evidence supported that all of these other beta-defensin genes are expressed at levels lower than that of the EBD gene in enteric tissue. Furthermore, some of these beta-defensin mRNAs were abundant in bone marrow, suggesting that in enteric tissue their expression may be in cells of hematopoietic origin. Extracts of small intestinal mucosa obtained from healthy cows have numerous active chromatographic fractions as determined by an antibacterial assay, and one peptide was partially purified. The peptide corresponded to one of the low-abundance cDNAs. This study provides evidence of beta-defensin expression in enteric tissue and that the mRNA encoding a major beta-defensin of enteric tissue, EBD, is inducibly expressed in enteric epithelial cells. These findings support the proposal that beta-defensins may contribute to host defense of enteric mucosa.
The structure of human parvovirus B19 (2004)

Human parvovirus B19 is the only parvovirus known to be a human pathogen. The structure of recombinant B19-like particles has been determined to approximately 3.5-A resolution by x-ray crystallography and, to our knowledge, represents the first near-atomic structure of an Erythrovirus. The polypeptide fold of the major capsid protein VP2 is a "jelly roll" with a beta-barrel motif similar to that found in many icosahedral viruses. The large loops connecting the strands of the beta-barrel form surface features that differentiate B19 from other parvoviruses. Although B19 VP2 has only 26% sequence identity to VP3 of adeno-associated virus, 72% of the C(alpha) atoms can be aligned structurally with a rms deviation of 1.8 A. Both viruses require an integrin as a coreceptor, and conserved surface features suggest a common receptor-binding region.
The EML4‐ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild‐type EGFR and KRAS (2009)

The EML4-ALK fusion gene was present in various histologic types of NSCLC. It occurred in mutual exclusion to EGFR and KRAS mutations and was associated with nonsmokers. The authors concluded that EML4-ALK may be useful for predicting the potential response to ALK inhibitors as a therapeutic option for patients with lung cancer.
Solid Supported Reaction of Substituted 2‐Oxazoline with Amines under Microwave Irradiation (2003)

Abstract 1,2‐Diaryl‐4‐phenylmethylene‐2‐imidazolin‐5‐ones were obtained by the interaction of primary amines with 2‐phenyl‐4‐phenylmethylene‐2‐oxazolin‐5‐one using acidic alumina or montmorillonite K10 clay under microwave irradiation (MWI). The same reaction over basic alumina gave arylamides of α‐arylamido‐β‐arylacrylic acids in good yield. Usage of acidic alumina for cyclization gave better results in comparison with clay. This procedure highlights the versatility of various solid supports.
Phytoecdysteroids Increase Protein Synthesis in Skeletal Muscle Cells (2008)

Phytoecdysteroids, which are structurally similar or identical to insect molting hormones, produce a range of effects in mammals, including increasing growth and physical performance. To study the mechanism of action of phytoecdysteroids in mammalian tissue, an in vitro cellular assay of protein synthesis was developed. In C2C12 murine myotubes and human primary myotubes, phytoecdysteroids increased protein synthesis by up to 20%. In vivo, ecdysteroids increased rat grip strength. Ecdysteroid-containing plant extracts produced similar results. The effect was inhibited by a phosphoinositide kinase-3 inhibitor, which suggests a PI3K-mediated mechanism.
Boronated Epidermal Growth Factor as a Potential Targeting Agent for Boron Neutron Capture Therapy of Brain Tumors (1996)

In order for boron neutron capture therapy (BNCT) to be successful, a large number (approximately 10(9)) of 10B atoms must be delivered to each cancer cell in order to sustain a lethal 10B(n, alpha)7Li reaction. The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and increased numbers of EGFR are found on the cell surface. If a sufficiently large number of 10B atoms could be attached to EGF, the resulting bioconjugates might be useful for targeting brain tumors. In order to accomplish this, we have boronated a fourth-generation starburst dendrimer (SD) using an isocyanato polyhedral borane, Na(CH3)3NB10H8NCO. For conjugation, reactive thiol groups were introduced into the boronated SD using N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP), and EGF was derivatized with m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester (sMBS). Subsequent reaction of thiol groups of derivatized BSD with maleimide groups of derivatized EGF produced stable BSD-EGF bioconjugates containing approximately 960 atoms of boron per molecule of EGF. As determined by electron spectroscopic imaging, the BSD-EGF initially was bound to the cell surface membrane and then was endocytosed, which resulted in accumulation of boron in lysosomes. The favorable in vitro properties of these bioconjugates suggest that they may be useful for the in vivo targeting of EGFR positive brain tumors.
Generation of human T-cell responses to an HLA-A2.1-restricted peptide epitope derived from alpha-fetoprotein. (1999)

Alpha-fetoprotein (AFP) is often derepressed in human hepatocellular carcinoma. Peptide fragments of AFP presented in the context of major histocompatibility molecules could serve as potential recognition targets by CD8 T cells, provided these lymphocytes were not clonally deleted in ontogeny. We therefore wished to determine whether the human T-cell repertoire could recognize AFP-derived peptide epitopes in the context of a common class I allele, HLA-A2.1. Dendritic cells genetically engineered to express AFP were capable of generating AFP-specific T-cell responses in autologous human lymphocyte cultures and in HLA-A2.1/Kb transgenic mice. These T cells recognize a 9-mer peptide derived from the AFP protein hAFP(542-550) (GVALQTMKQ). Identified as a potential A2.1-restricted peptide epitope from a computer analysis of the AFP sequence, hAFP(542-550) proved to have low binding affinity to A2.1, but slow off-kinetics. AFP-specific CTL- and IFN-gamma-producing cells recognize hAFP(542-550)-pulsed targets. Conversely, hAFP(542-550) peptide-generated T cells from both human lymphocyte cultures and A2.1/Kb transgenic mice recognized AFP-transfected targets in both cytotoxicity assays and cytokine release assays. These lines of evidence clearly demonstrate that AFP-reactive clones have not been deleted from the human T-cell repertoire and identify one immunodominant A2.1-restricted epitope. These findings also clearly establish AFP as a potential target for T-cell-based immunotherapy.
Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo (2001)

In 1986, Kärre and colleagues reported that natural killer (NK) cells rejected an MHC class I-deficient tumor cell line (RMA-S) but they did not reject the same cell line if it expressed MHC class I (RMA). Based on this observation, they proposed the concept that NK cells provide immune surveillance for "missing self," e.g., they eliminate cells that have lost class I MHC antigens. This seminal observation predicted the existence of inhibitory NK cell receptors for MHC class I. Here, we present evidence that NK cells are able to reject tumors expressing MHC class I if the tumor expresses a ligand for NKG2D. Mock-transfected RMA cells resulted in tumor formation. In contrast, when RMA cells were transfected with the retinoic acid early inducible gene-1 gamma or delta (RAE-1), ligands for the activating receptor NKG2D, the tumors were rejected. The tumor rejection was mediated by NK cells, and not by CD1-restricted NK1.1(+) T cells. No T cell-mediated immunological memory against the parental tumor was generated in the animals that had rejected the RAE-1 transfected tumors, which succumbed to rechallenge with the parental RMA tumor. Therefore, NK cells are able to reject a tumor expressing RAE-1 molecules, despite expression of self MHC class I on the tumor, demonstrating the potential for NK cells to participate in immunity against class I-bearing malignancies.
Synthesis, characterization and antimicrobial evaluation of some novelbenzenesulfonylhydrazone derivatives of benzimidazole (2015)

In the current research work, the synthesis of some new 2-(1H-benzo[d]imidazol-2-yl)-N-(4-(N’-substitutedphenylsulfonyl) benzohydrazide)benzamide derivatives(5a-5m) is described.The novel compounds were characterized using different spectroscopic methods. The new compounds were evaluated for antibacterial and antifungal activity. Assessment of the antibacterial andantifungal activities of these novel compounds against a different cell cultures revealed that compound 5d, 5k and 5m are the active ones.