gebhart/patrepeval huggingface dataset:
Genetic Mechanisms of Age Regulation of Human Blood Coagulation Factor IX (1999)

Blood coagulation capacity increases with age in healthy individuals. Through extensive longitudinal analyses of human factor IX gene expression in transgenic mice, two essential age-regulatory elements, AE5' and AE3', have been identified. These elements are required and together are sufficient for normal age regulation of factor IX expression. AE5', a PEA-3 related element present in the 5' upstream region of the gene encoding factor IX, is responsible for age-stable expression of the gene. AE3', in the middle of the 3' untranslated region, is responsible for age-associated elevation in messenger RNA levels. In a concerted manner, AE5' and AE3' recapitulate natural patterns of the advancing age-associated increase in factor IX gene expression.
Preventing wormhole attacks on wireless ad hoc networks: a graph theoretic approach (2005)

We study the problem of characterizing the wormhole attack, an attack that can be mounted on a wide range of wireless network protocols without compromising any cryptographic quantity or network node. A wormhole, in essence, creates a communication link between an origin and a destination point that could not exist with the use of the regular communication channel. Hence, a wormhole modifies the connectivity matrix of the network, and can be described by a graph abstraction of the ad hoc network. Making use of geometric random graphs induced by the communication range constraint of the nodes, we present the necessary and sufficient conditions for detecting and defending against wormholes. Using our theory, we also present a defense mechanism based on local broadcast keys. We believe our work is the first one to present analytical calculation of the probabilities of detection. We also present simulation results to illustrate our theory.
p16 gene homozygous deletions in acute lymphoblastic leukemia (1995)

The p16 protein is a cyclin inhibitor encoded by a gene located in 9p21, which may have antioncogenic properties, and is inactivated by homozygous p16 gene deletion or, less often, point mutation in several types of solid tumors often associated to cytogenetic evidence of 9p21 deletion. We looked for homozygous deletion and point mutation of the p16 gene in acute lymphoblastic leukemia (ALL), where 9p21 deletion or rearrangement are also nonrandom cytogenetic findings. Other hematologic malignancies including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), chronic lymphocytic leukemia (CLL), and myeloma were also studied. Homozygous deletion of the p16 gene was seen in 9 of the 63 (14%) ALL analyzed, including 6/39 precursor B-ALL, 3/12 T-ALL, and 0/12 Burkitt's ALL. Three of the 7 ALL with 9p rearrangement (including 3 of the 5 patients where this rearrangement was clearly associated to 9p21 monosomy) had homozygous deletion compared to 5 of the 55 patients with normal 9p (the last patient with homozygous deletion was not successfully karyotyped). Single stranded conformation polymorphism analysis of exons 1 and 2 of the p16 gene was performed in 88 cases of ALL, including the 63 patients analyzed by Southern blot. Twenty-six of the cases had 9p rearrangement, associated to 9p21 monosomy in at least 12 cases. A missense point mutation, at codon 49 (nucleotide 164), was seen in only 1 of the 88 patients. No homozygous deletion and no point mutation of the p16 gene was seen in AML, MDS, CLL, and myeloma. Homozygous deletion of interferon alpha genes (situated close to p16 gene in 9p21) was seen in only 3 of the 9 ALL patients with p16 gene homozygous deletion, and none of the ALL without p16 gene homozygous deletion. Our findings suggest that homozygous deletion of the p16 gene is seen in about 15% of ALL cases, is not restricted to cases with cytogenetically detectable 9p deletion, and could have a pathogenetic role in this malignancy. On the other hand, p16 point mutations are very rare in ALL, and we found no p16 homozygous deletions or mutations in the other hematologic malignancies studied.
Transplantation of Monocytes: A Novel Strategy for In Vivo Augmentation of Collateral Vessel Growth (2004)

Therapeutic augmentation of collateral vessel growth (arteriogenesis) is of particular clinical interest. Because monocytes localize to areas of collateral growth and create a highly arteriogenic environment through secretion of multiple growth factors, we tested the hypothesis that monocyte "homing" can therapeutically be exploited. We have used a rabbit model of arteriogenesis to investigate the therapeutic potential of transplanted rabbit monocytes that were either ex vivo stimulated or adenovirally transduced to express a transgene encoding an arteriogenic growth factor. The monocytes were intravenously injected 24 hr or 7 days after ligation of the animal's right femoral artery. Seven days after transplantation collateral flow was determined with a doppler flow probe and collateral vessels were quantified angiographically. Whereas transplantation of allogeneic cells (same species) resulted in a strong promotion of arteriogenesis, most likely through induction of local inflammation and recruitment of recipient monocytes, transplantation of autologous cells (same animal) was not able to significantly augment collateralization. However, when autologous monocytes were used as vehicles to deliver granulocyte macrophage-colony stimulating factor as therapeutic transgene, collateralization was strongly augmented. Their localization to the site of collateral development posttransplantation was demonstrated by ex vivo transduction with beta-galactosidase. Because isolation of monocytes is clinically widely available their ex vivo engineering and transplantation represents an intriguing new strategy for therapeutic arteriogenesis.
A Mechanism of the Irreversible Inactivation of Bovine Pancreatic Ribonuclease by Diethylpyrocarbonate (1970)

The irreversible inactivation of ribonuclease with diethylpyrocarbonate was studied. The products of the reaction were electrophoresed on polyacrylamide gels in sodium dodecyl sulfate and found to contain polymers of ribonuclease. Other proteins reacted similarly with diethylpyrocarbonate. Ribonuclease treated with maleic anhydride was unable to polymerize when treated with diethylpyrocarbonate, but when the N ‐maleyl group was removed by incubation at low pH, the capacity of the ribonuclease to polymerize was restored. It was concluded that the diethylpyrocarbonate reaction forms amide bonds between ɛ‐amino groups of lysine and carboxylic groups of aspartic or glutamic both intermolecularly or intramolecularly. In either case the enzyme was inactivated. A mechanism based on the known chemical reactivities of diethylpyrocarbonate is proposed. The conclusions are further substantiated by studies of tryptic peptides and microbiuret positive products obtained from a reaction of diethylpyrocarbonate with assorted amino acids.
Rapid Hypothesis Testing with Candida albicans through Gene Disruption with Short Homology Regions (1999)

Disruption of newly identified genes in the pathogen Candida albicans is a vital step in determination of gene function. Several gene disruption methods described previously employ long regions of homology flanking a selectable marker. Here, we describe disruption of C. albicans genes with PCR products that have 50 to 60 bp of homology to a genomic sequence on each end of a selectable marker. We used the method to disrupt two known genes, ARG5 and ADE2, and two sequences newly identified through the Candida genome project, HRM101 and ENX3. HRM101 and ENX3 are homologous to genes in the conserved RIM101 (previously called RIM1) and PacC pathways of Saccharomyces cerevisiae and Aspergillus nidulans. We show that three independent hrm101/hrm101 mutants and two independent enx3/enx3 mutants are defective in filamentation on Spider medium. These observations argue that HRM101 and ENX3 sequences are indeed portions of genes and that the respective gene products have related functions.
Exploration, normalization, and genotype calls of high-density oligonucleotide SNP array data (2006)

In most microarray technologies, a number of critical steps are required to convert raw intensity measurements into the data relied upon by data analysts, biologists, and clinicians. These data manipulations, referred to as preprocessing, can influence the quality of the ultimate measurements. In the last few years, the high-throughput measurement of gene expression is the most popular application of microarray technology. For this application, various groups have demonstrated that the use of modern statistical methodology can substantially improve accuracy and precision of the gene expression measurements, relative to ad hoc procedures introduced by designers and manufacturers of the technology. Currently, other applications of microarrays are becoming more and more popular. In this paper, we describe a preprocessing methodology for a technology designed for the identification of DNA sequence variants in specific genes or regions of the human genome that are associated with phenotypes of interest such as disease. In particular, we describe a methodology useful for preprocessing Affymetrix single-nucleotide polymorphism chips and obtaining genotype calls with the preprocessed data. We demonstrate how our procedure improves existing approaches using data from 3 relatively large studies including the one in which large numbers of independent calls are available. The proposed methods are implemented in the package oligo available from Bioconductor.
Strategies for gene disruption in Drosophila (2014)

Drosophila melanogaster has been a classic model organism for the studies of genetics. More than 15,000 Drosophila genes have been annotated since the entire genome was sequenced; however, many of them still lack functional characterization. Various gene-manipulating approaches in Drosophila have been developed for the function analysis of genes. Here, we summarize some representative strategies utilized for Drosophila gene targeting, from the unbiased ethyl methanesulfonate (EMS) mutagenesis and transposable element insertion, to insertional/replacement homologous recombination and site-specific nucleases such as the zinc-finger nuclease (ZFN), the transcription activator-like effector nuclease (TALEN) and the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system. Specifically, we evaluate the pros and cons of each technique in a historical perspective. This review discuss important factors that should be taken into consideration for the selection of a strategy that best fits the specific needs of a gene knockout project.
Anti‐tumor effects of tumor necrosis factor alone or combined with radiotherapy (1988)

Recombinant human tumor necrosis factor (rHuTNF) was investigated for its ability to increase the response of murine tumors to ionizing radiation. Both multiple i.v. administrations of rHuTNF and local tumor irradiation caused a significant delay in tumor growth. The effect of treatment with both agents combined was greater than the additive effect of the individual treatments. Furthermore, rHuTNF significantly increased tumor radiocurability, as assessed by the TCD50 assay. rHuTNF was not cytotoxic to tumor cells, nor did it affect their radiosensitivity. The in vivo anti-tumor effect of rHuTNF and its augmentation of tumor radioresponse were mediated through indirect mechanisms, either immunological or non-immunological. rHuTNF was also effective in reducing the damaging effect of ionizing radiation on bone-marrow progenitor cells, which could increase the therapeutic advantage of the rHuTNF-radiotherapy combination. These experiments suggest that rHuTNF is potentially beneficial in combination with radiotherapy.
The Role of Annexin II Tetramer in the Activation of Plasminogen (1998)

Annexin II tetramer (AIIt) is a major Ca2+-binding protein of endothelial cells which has been shown to exist on both the intracellular and extracellular surfaces of the plasma membrane. In this report, we demonstrate that AIIt stimulates the activation of plasminogen by facilitating the tissue plasminogen activator (t-PA)-dependent conversion of plasminogen to plasmin. Fluid-phase AIIt stimulated the rate of activation of [Glu]plasminogen about 341-fold compared with an approximate 6-fold stimulation by annexin II. AIIt bound to [Glu]plasminogen(S741C-fluorescein) with a Kd of 1. 26 +/- 0.04 microM (mean +/- S.D., n = 3) and this interaction resulted in a large conformational change in [Glu]plasminogen. Kinetic analysis established that AIIt produces a large increase of about 190-fold in the kcat, app and a small increase in the Km,app which resulted in a 90-fold increase in the catalytic efficiency (kcat/Km) of t-PA for [Glu]plasminogen. AIIt also stimulated the t-PA-dependent activation of [Lys]plasminogen about 28-fold. Furthermore, other annexins such as annexin I, V, or VI did not produce comparable activation of t-PA-dependent conversion of [Glu]plasminogen to plasmin. The stimulation of the activation of [Glu]plasminogen by AIIt was Ca2+-independent and inhibited by epsilon-aminocaproic acid. AIIt bound to human 293 cells potentiated t-PA-dependent plasminogen activation. AIIt that was bound to phospholipid vesicles or heparin also stimulated the activation of [Glu]plasminogen 5- or 11-fold, respectively. Furthermore, immunofluorescence labeling of nonpermeabilized HUVEC revealed a punctated distribution of AIIt subunits on the cell surface. These results therefore identify AIIt as a potent in vitro activator of plasminogen.
Synergistic and persistent effect of T‐cell immunotherapy with anti‐CD19 or anti‐CD38 chimeric receptor in conjunction with rituximab on B‐cell non‐Hodgkin lymphoma (2010)

Using artificial receptors, it is possible to redirect the specificity of immune cells to tumour-associated antigens, which is expected to provide a useful strategy for cancer immunotherapy. Given that B-cell non-Hodgkin lymphoma (B-NHL) cells invariably express CD19 and CD38, these antigens may be suitable molecular candidates for such immunotherapy. We transduced human peripheral T cells or a T-cell line with either anti-CD19-chimeric receptor (CAR) or anti-CD38-CAR, which contained an anti-CD19 or anti-CD38 antibody-derived single-chain variable domain respectively. Retroviral transduction led to anti-CD19-CAR or anti-CD38-CAR expression in T cells with high efficiency (>60%). The T cell line, Hut78, when transduced with anti-CD19-CAR or anti-CD38-CAR, exerted strong cytotoxicity against the B-NHL cell lines, HT and RL, and lymphoma cells isolated from patients. Interestingly, use of both CARs had an additive cytotoxic effect on HT cells in vitro. In conjunction with rituximab, human peripheral T cells expressing either anti-CD19-CAR or anti-CD38-CAR enhanced cytotoxicity against HT-luciferase cells in xenografted mice. Moreover, the synergistic tumour-suppressing activity was persistent in vivo for over 2 months. These results provide a powerful rationale for clinical testing of the combination of rituximab with autologous T cells carrying either CAR on aggressive or relapsed B-NHLs.
Comparison of Inverted Centrifugation, Saline Washing, and Dextran Sedimentation in the Preparation of Leukocyte‐Poor Red Cells (1973)

Three methods (inverted centrifugation; inverted centrifugation followed by continuous‐flow washing in 5 per cent dextrose‐saline; and dextran sedimentation followed by continuous‐flow washing in 5 per cent dextrose‐saline) were evaluated for the preparation of leukocyte‐poor red blood cells. Residual leukocyte contents were 0.32, 0.40, and 0.16 billion per 100 g of erythrocytes and erythrocyte losses were 24, 42, and 35 per cent, respectively, for the three methods. The mean removal of leukocytes per unit after inverted centrifugation was 80 per cent. Continuous‐flow washing after inverted centrifugation did not remove additional leukocytes. Dextran sedimentation removed a mean 92 per cent of leukocytes. Residual dextran was not detected in the terminal wash solution. These findings suggest dextran sedimentation may be useful for preparing leukocyte‐poor red blood cells for preventing sensitization to leukocytes in high risk recipients such as transplantation candidates.
Preassociation of STAT1 with STAT2 and STAT3 in Separate Signalling Complexes Prior to Cytokine Stimulation (1996)

A variety of cytokines and growth factors act through an induction of gene expression mediated by a family of latent transcription factors called STAT (signal transducers and activators of transcription) proteins. Ligand-induced tyrosine phosphorylation of the STATs promotes their homodimer and heterodimer formation and subsequent nuclear translocation. We demonstrate here that STAT protein heterocomplexes exist prior to cytokine treatment. When unstimulated HeLa cells are ruptured in hypotonic buffer without salt or detergent, immunoadsorption of either STAT1 or STAT2 from the resulting cytosol yields coimmunoadsorption of the other STAT protein. Similarly, STAT1-STAT3 heterocomplexes are coimmunoadsorbed from hypotonic cytosol. STAT1 and STAT2 or STAT1 and STAT3 translated in reticulocyte lysate spontaneously form heterocomplexes when the translation lysates are mixed at 0 degrees C. Our data suggest that interferon-alpha /beta-induced tyrosine phosphorylation increases the stability of a preexisting, latent, STAT1-STAT2 signaling complex. Newly translated STAT1 binds in equilibrium fashion to STAT2 and STAT3, but we show that STAT2 and STAT3 exist in separate heterocomplexes with STAT1, consistent with a model in which STAT1 contains a common binding site for other STAT proteins.
IL-10: The Master Regulator of Immunity to Infection (2008)

IL-10 is an anti-inflammatory cytokine. During infection it inhibits the activity of Th1 cells, NK cells, and macrophages, all of which are required for optimal pathogen clearance but also contribute to tissue damage. In consequence, IL-10 can both impede pathogen clearance and ameliorate immunopathology. Many different types of cells can produce IL-10, with the major source of IL-10 varying in different tissues or during acute or chronic stages of the same infection. The priming of these various IL-10-producing populations during infections is not well understood and it is not clear whether the cellular source of IL-10 during infection dictates its cellular target and thus its outcome. In this article we review the biology of IL-10, its cellular sources, and its role in viral, bacterial, and protozoal infections.
Using clustering algorithms in legacy systems remodularization (2002)

Incited by the observation that cluster analysis and the remodularization of software systems solve similar problems, we have done research in both these areas in order to provide theoretical background for the application of cluster analysis in systems remodularization. We present an overview of cluster analysis and of systems remodularization. It appears that system remodularization techniques often either reinvent clustering techniques or could be augmented by them. We also give directions for further research.
Translating the COPD Transcriptome: Insights into Pathogenesis and Tools for Clinical Management (2008)

While the role cigarette smoke plays in chronic obstructive pulmonary disease (COPD) is undisputed, the molecular mechanisms by which inhaled smoke contributes to disease pathogenesis remains unclear. One of the major barriers to effective approaches to diagnose and manage COPD is the remarkable heterogeneity displayed by patients with the disease. Whole-genome gene-expression studies of airway and lung tissue from patients with COPD provide an opportunity to gain insights into disease pathogenesis, allowing for both a molecular understanding of the pathogenic processes that contribute to this heterogeneity, and the ability to target therapies to these processes. This review focuses on synthesizing and integrating the limited numbers of high-throughput gene expression studies that have been conducted on lung tissue and airway samples from smokers with COPD. Comparing several lung tissue studies using computational approaches, we find that the results suggest fundamental similarities and identify common biological processes underlying COPD, despite each study having identified largely nonoverlapping lists of differentially expressed genes. Given these similarities, we argue that additional lung tissue and airway gene-expression studies are warranted, and present a roadmap for how such studies could lead to clinically relevant tools that would impact COPD management.
Modifications of bovine prothrombin fragment 1 in the presence and absence of Ca(II) ions. Loss of positive cooperativity in Ca(II) ion binding for the modified proteins. (1992)

Chemical modification of bovine prothrombin fragment 1 according to the procedure of D. J. Welsch and G. L. Nelsestuen (1988) [Biochemistry 27, 4946-4952 and ealier papers] provided a series of fragment 1 derivatives in which various nitrogen-containing side chains were N-acetylated and/or N-2,4,6-trinitrophenylated. In addition the des-[Ala-1,Asn-2]- and des-[Ala-1,Asn-2,Lys-3]-fragment 1 derivatives were prepared by limited enzymatic hydrolysis of fragment 1 using cathepsin C and plasmin, respectively. Quantitative studies on the Ca(II) binding of these proteins have been accomplished using 45Ca(II) equilibrium dialysis. Binding of these fragment 1 derivatives to phosphatidylserine/phosphatidylcholine (PS/PC) vesicles (25:75) in the presence of Ca(II) ions has been studied using the light-scattering technique. Acylation of the 5 lysine residues of fragment 1 by the action of acetic anhydride (500-fold molar excess) in the presence of 75 mM Ca(II), pH 8.0, results in loss of positive cooperativity in Ca(II) binding (Scatchard plot) and an increase in the number of Ca(II) ions bound. The Ca(II)-dependent PS/PC binding of the acylated protein is reduced. Removal of 2 and 3 residues from the amino terminus likewise leads to loss of positive cooperativity in Ca(II) binding and reduced binding affinity to PS/PC vesicles. The important role of the amino-terminal 1-10 sequence is discussed. We conclude that positive cooperativity in Ca(II) binding is not a prerequisite for the Ca(II)-dependent binding of bovine prothrombin fragment 1 to PS/PC vesicles.
Roles of Ion Pairing on Electroreduction of Dioxygen in Imidazolium-Cation-Based Room-Temperature Ionic Liquid (2008)

The ion-pairing phenomenon during the dioxygen (O2) reduction reaction (ORR) in a room-temperature ionic liquid (RTIL) was recognized and extensively studied using a voltammetric technique. Cyclic voltammetric two one-electron ORRs at a gold electrode in dimethyl sulfoxide (DMSO) solution containing 0.1 M tetraethylammonium perchlorate and in 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIBF4) RTIL were carried out, and the obtained results were compared. Two cathodic peaks at −0.71 and −1.35 V versus Ag|AgCl|NaCl (sat.) and a well-defined anodic peak at −0.71 V and two ill-defined anodic peaks at potentials more positive than −0.2 V were observed in EMIBF4. The first and second cathodic peak potentials obtained in EMIBF4 were by 0.07 and 0.65 V more positive than those observed for the reductions of O2 to superoxide (O2•-) and O2•- to peroxide (O22-) in DMSO solution, respectively. Such a potential shift in the ORR was considered to be due to the ion-paring phenomenon as observed in the redox reaction of 1,4-benzoquinone in DMSO in the presence of EMIBF4. A 57 mV positive shift of the midpoint potential of the O2/O2•- redox couple with a 10-fold increase of EMIBF4 in DMSO solution was obtained. The association constant and free-energy change (ΔG) of the ion-pairing were determined to be 13.5 M-1 and −6.4 kJ mol-1, respectively. The value of ΔG for the comproportionation reaction of O22- and O2 to form O2•- in EMIBF4 solution (−61.7 kJ mol-1) was one-half of that in DMSO solution (−117.7 kJ mol-1), suggesting a favorable stability of O22- in EMIBF4.