gebhart/patrepeval huggingface dataset:
Combining Network Modeling and Gene Expression Microarray Analysis to Explore the Dynamics of Th1 and Th2 Cell Regulation (2010)

Two T helper (Th) cell subsets, namely Th1 and Th2 cells, play an important role in inflammatory diseases. The two subsets are thought to counter-regulate each other, and alterations in their balance result in different diseases. This paradigm has been challenged by recent clinical and experimental data. Because of the large number of genes involved in regulating Th1 and Th2 cells, assessment of this paradigm by modeling or experiments is difficult. Novel algorithms based on formal methods now permit the analysis of large gene regulatory networks. By combining these algorithms with in silico knockouts and gene expression microarray data from human T cells, we examined if the results were compatible with a counter-regulatory role of Th1 and Th2 cells. We constructed a directed network model of genes regulating Th1 and Th2 cells through text mining and manual curation. We identified four attractors in the network, three of which included genes that corresponded to Th0, Th1 and Th2 cells. The fourth attractor contained a mixture of Th1 and Th2 genes. We found that neither in silico knockouts of the Th1 and Th2 attractor genes nor gene expression microarray data from patients with immunological disorders and healthy subjects supported a counter-regulatory role of Th1 and Th2 cells. By combining network modeling with transcriptomic data analysis and in silico knockouts, we have devised a practical way to help unravel complex regulatory network topology and to increase our understanding of how network actions may differ in health and disease.
Oxazolone‐induced murine model of ulcerative colitis (2004)

Oxazolone colitis is Th2-mediated and has similar histologic features and distribution of inflammation to ulcerative colitis (UC), which has important implications for the use of this model in the study of the pathogenesis and treatment of UC.
Prevention of the Decrease in Sensitivity of an Amperometric Glucose Sensor in Undiluted Human Serum (1999)

reported increased fecal uroporphyrin in two of three patients with AIP and all four patients with VP.Because our three patients were excreting high concentrations of urine PBG at the time of fecal collection, their serum PBG was probably increased.If this is the source of fecal uroporphyrin, it probably would also be seen during acute attacks of the other acute porphyrias, as has been reported for VP (12).HCP was excluded from the differential diagnosis in all three cases by the low proportion of fecal coproporphyrin III (2) and by the proportion of coproporphyrin I exceeding coproporphyrin III for all three cases (13).VP is characterized by a fecal porphyrin trace in which protoporphyrin predominates (2) and was excluded because protoporphyrin was Ͻ5% of the total porphyrin in all three patients.We therefore concluded that all three patients have AIP with increased fecal porphyrins and an increased fecal uroporphyrin fraction.The source of the uroporphyrin is probably the nonenzymatic condensation of PBG produced during the acute attack and excreted into the bile.Fecal uroporphyrin in patients excreting excess PBG could, therefore, be a feature of the acute attack in any of the three acute porphyrias.I thank D. Blake and V.
RELATIONSHIP OF LEUKOPENIA TO 6MP INDUCED REMISSION OF CROHN'S DISEASE (CD) (1998)

8 A previous report (Am J Gastro 1994;89:362) suggests that leukopenia due to 6-mercaptopurine (6MP) promotes clinical remission in adults with active CD. As part of a prospective multicenter trial we evaluated the frequency of leukopenia and its relationship to induction of clinical CD remission by 6MP. Methods: 55 children (ages 13±2 yrs) with moderate-severe CD were randomized within 6 wks of initial diagnosis to 6MP (1.5 mg/kg/day) + prednisone (Grp1) or placebo + prednisone (Grp2). In both groups pred was started at 40 mg/day, weaned per defined schedule based on change in CD activity score, & discontinued as remission was achieved. WBC counts were obtained at 0, 1, 2 & 6 months, and percent change from baseline calculated. The temporal relationship of leukopenia (WBC<4,000/mm3) to onset of remission was noted. Statistical significance required p<0.01. Results: Grp1 and Grp2 were comparable for age, sex, site of CD & initial CD activity score. Both groups had similar cumulative pred dose at 2 & 6 months, but by 12 months it was significantly lower (p<0.008) in Grp1 than Grp2. At 1 mos, 25/27 Grp1 and 22/28 Grp2 subjects had inactive disease (p=NS). By 3 mos, 85% of both groups were in remission. Remission was maintained to 12 mos in 23/24 (96%) Grp1 but in only 15/25 (60%) Grp2 (p<0.004). Median WBC at baseline differed (Grp1 7.3 IQR 3.9; Grp2 10.3 IQR 4.3; p=0.01). Percent increases over baseline in median WBC at 2 mos (20-30%) and percent decreases at 6 mos (-10 to -30%) were similar in both groups. One subject had leukopenia at study onset. During 12 mos of study, 6 Grp1 & 0 Grp2 subjects had leukopenia (p=0.03). Four of 6 with leukopenia had a clinical remission with WBC>4000. Overall, active CD remitted without leukopenia in 22 Grp1 subjects. The lowest recorded WBC=3,100 and absolute neutrophil count=1221. No significant infections or adverse reactions were reported. Conclusions: Newly diagnosed children with moderate-severe CD treated with 6MP + pred require less steroid and maintain remission longer than those treated with pred alone. 6MP + pred is safe and does not require leukopenia to induce CD remission.
Restriction of the in vitro and in vivo tyrosine protein kinase activities of pp60c-src relative to pp60v-src. (1985)

The tyrosine protein kinase activities of pp60c-src and pp60v-src were compared. The activities were qualitatively similar in vitro when the src proteins were bound in an immune complex with monoclonal antibody; both proteins utilized either ATP or GTP as phosphate donors, preferred Mn2+ to Mg2+, and had similar exogenous substrate specificities. The specific activity of pp60c-src was about 10-fold lower than that of pp60v-src for exogenous substrate phosphorylation but was only 1.1- to 2-fold lower than that of pp60v-src for autophosphorylation. Six glycolytic enzymes, including three not previously identified as substrates for pp60src phosphorylation, were phosphorylated by both pp60c-src and pp60v-src. Levels of pp60c-src fourfold higher than the amount of pp60v-src in src-plasmid-transformed cells did not detectably alter the level of phosphotyrosine in cellular proteins, but increasing the expression of pp60c-src another twofold (which induces cells to form foci in monolayer culture (P.J. Johnson, P.M. Coussens, A.V. Danko, and D. Shalloway, Mol. Cell. Biol. 5:1073-1083, 1985) resulted in a threefold increase in the level of cellular protein phosphotyrosine. Immunoprecipitation and analysis of the alkali-stable phosphoproteins by two-dimensional electrophoresis showed that, in contrast to pp60v-src-transformed cells, pp36 and enolase are only weakly phosphorylated in these high-level pp60c-src overexpresser cells. Even allowing for the in vitro differences in specific activities of phosphorylation, these results suggest that the pp60c-src tyrosine protein phosphorylating activity may be restricted relative to that of pp60v-src by additional in vivo mechanisms.
Androgen Receptor Antagonists in Castration-Resistant Prostate Cancer (2013)

Persistent androgen receptor (AR) signaling despite low levels of serum androgens has been identified as a critical target for drug discovery in castration-resistant prostate cancer (CRPC). As proof of principle that the AR remains relevant in CRPC, 2 AR-targeted agents recently approved by the Food and Drug Administration-abiraterone and enzalutamide-have increased overall survival for patients with CRPC in the setting of prior chemotherapy. This review focuses on the AR and 2 direct antagonists, enzalutamide and ARN-509. These next-generation AR antagonists offer great promise for patients with advanced disease. Relative to conventional antiandrogens such as bicalutamide, they bind to the receptor with higher affinity, prevent nuclear translocation and DNA binding, and induce apoptosis without agonist activity in preclinical models. The success of these AR-targeted agents in the clinic has changed the landscape of therapy for patients with CRPC, and further therapeutic options building on this platform are currently in development.
Non‐steroidal anti‐oestrogens inhibit the differentiation of synovial macrophages into dendritic cells (2001)

By inhibiting the differentiation of SF macrophages into DC, non-steroidal anti-oestrogens may have beneficial effects in RA.
Iron Sources Used by the Nonpathogenic Lactic Acid Bacterium Lactobacillus sakei as Revealed by Electron Energy Loss Spectroscopy and Secondary-Ion Mass Spectrometry (2009)

Lactobacillus sakei is a lactic acid bacterium naturally found on meat. Although it is generally acknowledged that lactic acid bacteria are rare species in the microbial world which do not have iron requirements, the genome sequence of L. sakei 23K has revealed quite complete genetic equipment dedicated to transport and use of this metal. Here, we aimed to investigate which iron sources could be used by this species as well as their role in the bacterium's physiology. Therefore, we developed a microscopy approach based on electron energy loss spectroscopy (EELS) analysis and nano-scale secondary-ion mass spectrometry (SIMS) in order to analyze the iron content of L. sakei cells. This revealed that L. sakei can use iron sources found in its natural ecosystem, myoglobin, hemoglobin, hematin, and transferrin, to ensure long-term survival during stationary phase. This study reveals that analytical image methods (EELS and SIMS) are powerful complementary tools for investigation of metal utilization by bacteria.
Differential antagonism of Ras biological activity by catalytic and Src homology domains of Ras GTPase activation protein. (1993)

Ras p120 GTPase activation protein (GAP), a cytosolic protein, is a negative mediator and potential downstream effector of Ras function. Since membrane association is critical for Ras function, we introduced the Ras membrane-targeting signal (a 19-residue peptide ending in CAAX, where C = cysteine, A = aliphatic amino acid, and X = any amino acid) onto the GAP N-terminal Src homology 2 and 3 and the C-terminal catalytic domains (designated nGAP/CAAX and cGAP/CAAX, respectively) to determine the role of membrane association in GAP function. cGAP/CAAX and full-length GAP/CAAX, but not GAP or nGAP/CAAX, exhibited potent growth inhibitory activity. Whereas both oncogenic and normal Ras activity were inhibited by cGAP/CAAX, nGAP/CAAX, despite lacking the Ras binding domain, inhibited the activity of oncogenic Ras without affecting the action of normal Ras. Altogether, these results demonstrate that membrane association potentiates GAP catalytic activity, support an effector function for GAP, and suggest that normal and oncogenic Ras possess different downstream interactions.
Cyclin D1 G870A Polymorphism Contributes to Colorectal Cancer Susceptibility: Evidence from a Systematic Review of 22 Case-Control Studies (2012)

The available evidence demonstrates that the CCND1 870A allele might be a low-penetrant risk factor for colorectal cancer.
Bipolar Microsecond Pulses and Insulated Needle Electrodes for Reducing Muscle Contractions During Irreversible Electroporation (2017)

The study provides guidance for treatment planning and reducing muscle contractions in the clinical application of H-FIRE.
Dendritic cell activating peptides induce distinct cytokine profiles (2006)

High-mobility group box 1 protein (HMGB1), a DNA-binding nuclear and cytosolic protein, is a pro-inflammatory cytokine released by monocytes and macrophages. HMGB1 as well as its B box domain induce maturation of human dendritic cells (DCs). This report demonstrates that the B box domain induces phenotypic maturation of murine bone marrow-derived dendritic cells (BM-DCs) as evidenced by increased CD86, CD40 and MHC-II expression. The B box domain enhanced secretion of pro-inflammatory cytokines and chemokines: IL-1beta, IL-2, IL-5, IL-8, IL-12 and tumor necrosis factor (TNF)-alpha, but not IL-6 and IL-10. Furthermore, four peptides whose sequences correspond to different regions of HMGB1 induced production of IL-1beta, IL-2 and IL-12 (p70), but not IL-10 and IL-6 in mouse BM-DCs. Interestingly, these peptides differed in their capacity to induce TNF-alpha, IL-5, IL-18 and IL-8. B box domain as well as peptide-activated DCs acted as potent stimulators of allogeneic T cells in a mixed leukocyte reaction. DCs exposed to HMGB1 peptides induced proliferation of ovalbumin-specific syngeneic T cells. These DC-activating peptides could serve as an adjuvant in immunotherapeutic or vaccine context and the selective activity of these different peptides suggests a means to customize the functional properties of DCs.
Intensification of Freeze‐Drying for the Pharmaceutical and Food Industries (2014)

This chapter contains sections titled: Introduction Exergetic Analysis (and Optimization) of the Freeze-Drying Process Process Intensification in Vacuum Freeze-Drying of Liquids Atmospheric Freeze-Drying Use of Combined Technologies for Drying Heat-Sensitive Products Continuous Freeze-Drying Conclusions
BAND-NOTCHED UWB CROSSED SEMI-RING MONOPOLE ANTENNA (2011)

A novel type of ultra-wide band (UWB) crossed semi-ring monopole antenna with band notched characteristics is presented. The proposed antenna consists of a wideband crossed semi-ring monopole and four L-shaped slots, producing band-notched characteristic. Efiects of the various parameters for antenna performances are discussed. The central frequency and bandwidth of the notched band can be controlled easily by adjusting three key design parameters. A prototype is constructed and measured flnally.
Modern approaches to wettability : theory and applications (1992)

The Modern Theory of Contact Angles and the Hydrogen Bond Component of Surface Energies (R.J. Good, C.J. van Oss). The LongRange Attraction Between Macroscopic Hydrophobic Surfaces (H.K. Cristenson). High and MediumEnergy Surfaces (M.E. Schrader). Determination of the Surface Energy of Solids by the Two Liquid Phase Method (J. Schultz, M. Nardin). The Equation of State Approach to Interfacial Tensions (J.K. Spelt et al.). Thermal Reconstruction of the Functionalized Interface of Polyethylene Carboxylic Acid and its Derivatives (G.S. Ferguson, G.M. Whitesides). Block Copolymers and Hydrophilicity (A. Takahara). Wettability and Bioadhesion in Ophthalmology (F.J. Holly). Wettability of Surfaces in the Oral Cavity (H.J. Busscher). Wettability as a Surface Signal for Aquatic Organisms (G.I. Loeb, J.W. Mihm). Wettability of Clay Minerals (S. Yariv). 5 additional articles. Index.
DNAlignTT: Pairwise DNA alignment with sequence specific transition-transversion ratio (2008)

Pairwise DNA and protein sequence alignment is an important task in bioinformatics which forms the basis of many other tasks like multiple sequence alignment, protein structure and function prediction, phylogenetic analysis. In general, more emphasis is given to protein sequence alignment, and the alignment methods designed for protein sequences can usually be used with little modification for DNA sequences as well. However, it is desirable to design methods specifically for DNA alignments, making use of specific DNA sequence models and if possible, also of the specific sequences being aligned. In this paper, we present an iterative method for DNA sequence alignment with sequence specific transition-transversion ratio. Preliminary experiments indicate that the proposed technique has significant potential. The approach better suits to the nature of the specific DNA sequence pair, and could be a significant step in the direction of using sequence specific substitution matrices for DNA sequences.
Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers (2005)

Hepsin is a membrane-anchored, trypsin-like serine protease with prominent expression in the human liver and tumours of the prostate and ovaries. To better understand the biological functions of hepsin, we identified macromolecular substrates employing a tetrapeptide PS-SCL (positional scanning-synthetic combinatorial library) screen that rapidly determines the P1-P4 substrate specificity. Hepsin exhibited strong preference at the P1 position for arginine over lysine, and favoured threonine, leucine or asparagine at the P2, glutamine or lysine at the P3, and proline or lysine at the P4 position. The relative activity of hepsin toward individual AMC (7-amino-4-methylcoumarin)-tetrapeptides was generally consistent with the overall peptide profiling results derived from the PC-SCL screen. The most active tetrapeptide substrate Ac (acetyl)-KQLR-AMC matched with the activation cleavage site of the hepatocyte growth factor precursor sc-HGF (single-chain HGF), KQLR downward arrowVVNG (where downward arrow denotes the cleavage site), as identified by a database analysis of trypsin-like precursors. X-ray crystallographic studies with KQLR chloromethylketone showed that the KQLR peptide fits well into the substrate-binding cleft of hepsin. This hepsin-processed HGF induced c-Met receptor tyrosine phosphorylation in SKOV-3 ovarian cancer cells, indicating that the hepsin-cleaved HGF is biologically active. Activation cleavage site mutants of sc-HGF with predicted non-preferred sequences, DPGR downward arrowVVNG or KQLQ downward arrowVVNG, were not processed, illustrating that the P4-P1 residues can be important determinants for substrate specificity. In addition to finding macromolecular hepsin substrates, the extracellular inhibitors of the HGF activator, HAI-1 and HAI-2, were potent inhibitors of hepsin activity (IC50 4+/-0.2 nM and 12+/-0.5 nM respectively). Together, our findings suggest that the HGF precursor is a potential in vivo substrate for hepsin in tumours, where hepsin expression is dysregulated and may influence tumorigenesis through inappropriate activation and/or regulation of HGF receptor (c-Met) functions.
A stable crystalline carbene (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA stable crystalline carbeneAnthony J. Arduengo III, Richard L. Harlow, and Michael KlineCite this: J. Am. Chem. Soc. 1991, 113, 1, 361–363Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://pubs.acs.org/doi/10.1021/ja00001a054https://doi.org/10.1021/ja00001a054research-articleACS PublicationsRequest reuse permissionsArticle Views30534Altmetric-Citations3599LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Transitional B cells are the target of negative selection in the B cell compartment. (1995)

B lymphocytes recognize antigen through membrane-bound antigen-receptors, membrane IgM and IgD (mIgM and mIgD). Binding to foreign antigens initiates a cascade of biochemical events that lead to activation and differentiation. In contrast, binding to self-antigens leads to death or to inactivation. It is commonly believed that the B cells acquire the ability to discriminate between self and nonself in the early phases of development. We report here that immature B cells, which have just emerged from the mIgMneg, B220pos pool, are not deleted upon binding of self-antigen. In vivo, developing B cells become sensitive to tolerance induction in a relatively late window of differentiation, when they are in transition from the immature (HSAbright, B220dull) to the mature (HSAdull, B220bright) stage. In the transitional B cells, early markers of differentiation such as Pgp1 (CD44) and ThB reach the highest level of expression, while the expression of CD23 and mIgD, late markers of differentiation, and expression of class II MHC, progressively increases. Most of the transitional B cells, but only few of the mature and of the immature B cells, express the fas antigen, while mature B cells, but not immature and transitional B cells, express bcl-2 protein. mIgM is present in low amounts in immature B cells, reaches the highest level of expression in transitional B cells and is down-regulated in mature resting B cells, where it is coexpressed with mIgD. The high expression of mIgM, the presence of the fas antigen and the absence of bcl-2 protein is compatible with the high sensitivity of transitional B cells to negative selection. In vitro, immature B cells die rapidly by apoptosis after cross-linking of mIgM. This result, combined with the resistance of immature B cells to elimination in vivo, suggests that early in development the stroma cell microenvironment modulates signals transduced through mIgM. The functional and phenotypic division of IgMpos bone marrow B cells in three compartments not only allows to define the target population of physiological processes like negative selection, but will also be a helpful tool for an accurate description of possible developmental blocks in mutant mice.
Influence Of Hypoxia And Hypoxia-Reoxygenation On Endothelial P-Selectin Expression (1996)

P-selectin is an endothelial adhesion molecule involved in the initial step of the neutrophil recruitment. We investigated the effect of hypoxia (95% N2, 5% CO2) and of hypoxia-reoxygenation (95% air, 5% CO2) on the expression of P-selectin by human umbilical vein endothelial cells (HUVEC). P-selectin expression was detected by immunolabelling and quantified by flow cytometric analysis. Our data indicate that hypoxia induces an increase in P-selectin expression with a maximum reached after 90 minutes. A hypoxic exposure of 90 minutes results in a highly significant increase compared to normoxia (p < 0.001, n = 13). Furthermore, when a reoxygenation period follows 90 minutes of hypoxia, the initially elevated levels of P-selectin are dramatically enhanced with a maximum obtained after 60 minutes of reoxygenation.