gebhart/patrepeval huggingface dataset:
Functional cooperation between the neural adhesion molecules L1 and N-CAM is carbohydrate dependent. (1990)

The neural cell adhesion molecules L1 and N-CAM have been suggested to interact functionally by formation of a complex between the two molecules (Kadmon, G., A. Kowitz, P. Altevogt, and M. Schachner. 1990. J. Cell Biol. 110:193-208). To determine the molecular mechanisms underlying this functional cooperation, we have studied the contribution of carbohydrates to the association of the two molecules at the cell surface. Aggregation or adhesion between L1- and N-CAM-positive neuroblastoma N2A cells was reduced when the synthesis of complex and/or hybrid glycans was modified by castanospermine. Fab fragments of polyclonal antibodies to L1 inhibited aggregation and adhesion of castanospermine-treated cells almost completely, whereas untreated cells were inhibited by approximately 50%. Fab fragments of polyclonal antibodies to N-CAM did not interfere with the interaction between castanospermine-treated cells, whereas they inhibited aggregation or adhesion of untreated cells by approximately 50%. These findings indicate that cell interactions depending both on L1 and N-CAM ("assisted homophilic" binding) can be reduced to an L1-dominated interaction ("homophilic binding"). Treatment of cells with the carbohydrate synthesis inhibitor swainsonine did not modify cell aggregation in the absence or presence of antibodies compared with untreated cells, indicating that castanospermine-sensitive, but swainsonine-insensitive glycans are involved. To investigate whether the appropriate carbohydrate composition is required for an association of L1 and N-CAM in the surface membrane (cis-interaction) or between L1 on one side and L1 and N-CAM on the other side of interacting partner cells (trans-interaction), an L1-positive lymphoid tumor cell line was coaggregated with and adhered to neuroblastoma cells in the various combinations of castanospermine-treated and untreated cells. The results show that it is the cis-interaction between L1 and N-CAM that depends on the appropriate carbohydrate structures.
The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations (2008)

Characterization of the molecular pathways that are required for the viability and maintenance of self-renewing tumor-initiating cells may ultimately lead to improved therapies for cancer. In this study, we show that a CD133(+)/CD44(+) population of cells enriched in prostate cancer progenitors (PCaPs) has tumor-initiating potential and that these progenitors can be expanded under nonadherent, serum-free, sphere-forming conditions. Cells grown under these conditions have increased in vitro clonogenic and in vivo tumorigenic potential. mRNA expression analysis of cells grown under sphere-forming conditions, compared with long-term monolayer cultures, revealed preferential activation of the PI3K/AKT signaling pathway. PI3K p110alpha and beta-protein levels were higher in cells grown under sphere-forming conditions, and phosphatase and tensin homolog (PTEN) knockdown by shRNA led to an increase in sphere formation as well as increased clonogenic and tumorigenic potential. Similarly, shRNA knockdown of FoxO3a led to an increase in tumorigenic potential. Consistent with these results, inhibition of PI3K activity by the dual PI3K/mTOR inhibitor NVP-BEZ235 led to growth inhibition of PCaPs. Taken together, our data strongly suggest that the PTEN/PI3K/Akt pathways are critical for prostate cancer stem-like cell maintenance and that targeting PI3K signaling may be beneficial in prostate cancer treatment by eliminating prostate cancer stem-like cells.
Multimerization behaviour of single chain Fv variants for the tumour-binding antibody B72.3 (1994)

A systematic study has been performed on the relationship between linker length, relative orientation of variable domains, multimerization behaviour and antigen binding activity for single chain Fvs (scFvs) of the tumour-binding antibody B72.3. Thirteen scFv variants with linkers comprising up to six repeats of the motif Gly-Gly-Gly-Gly-Ser were studied. All these scFvs showed a tendency to form dimers or higher molecular weight species, and this tendency decreased with increasing linker length. The dimers and higher molecular weight forms may arise from head to tail intermolecular association of VH and VL domains. For each linker length, scFvs with the organization VL-linker-VH showed greater binding activity than those with the organization VH-linker-VL. In fact, for the latter organization only the variant with a 30 amino acid linker showed good binding activity, suggesting that (i) for B72.3 the C-terminus of VH or the N-terminus of VL makes a structural contribution to antigen binding, and (ii) shorter linkers interfere with this contribution. Antigen binding studies on scFvs should be interpreted with caution because of their tendency to multimerize. Such multimerization can be minimized by using linkers longer than those in common use.
Keyword recognition using template concatenation (2005)

The error rates typically reported for connected speech recognition (CSR) and keyword recognition (KWR) differ by at least an order of magnitude. We present a simple new KWR method and use the new method to investigate the factors that are responsible for this large apparent "performance gap". The new KWR method concatenates templates to match all the input speech, and can utilize knowledge about the vocabulary and syntax of the input speech. We present performance results for systems that differ in the following factors: syntax, speaker training, and template vocabulary. The results suggest that template-concatenation KWR methods can give good results for unrestricted input speech.
Magnetic materials for MEMS applications (2004)

This topical review discusses magnetic microelectromechanical systems (MagMEMS). A number of exemplars are drawn from the authors' own work, and a review is given of other significant literature in the area. The case is made that MagMEMS offer unique features over conventional MEMS, such as remote interrogation and self-test. A review of the key magnetic principles and magnetic materials is included by way of a guide to the general reader. Finally, a roadmap for the future development of MagMEMS is set out.
Complement and neutrophil activation in the pathogenesis of ischemic myocardial injury. (1988)

Complement depletion with cobra venom factor (CVF) before coronary artery ligation has been previously shown to reduce subsequent ischemic myocardial tissue injury in the baboon; however, whether complement depletion after the initiation of acute myocardial ischemia affords similar myocardial preservation is not known. Both complement depletion with CVF or the administration of certain nonsteroidal anti-inflammatory drugs, including ibuprofen, are thought to decrease myocardial infarct size by reducing polymorphonuclear leukocytic (PMN) infiltration; nevertheless, complement activation also could alter tissue injury by PMN-independent actions. Thus, the relative effects of CVF administered after coronary artery ligation on the subsequent development of myocardial tissue injury were assessed in a baboon myocardial infarction model. The animals were randomized into three treatment groups (n = 6): either CVF (125 units/kg) or saline was given 30 minutes after coronary artery ligation, and ibuprofen (12.5 mg/kg) was administered 30 minutes and 4 hours after ligation. The extent of ischemic myocardial injury was assessed 24 hours later. Relative to saline-treated baboons, both CVF and ibuprofen reduced PMN infiltration (36 +/- 4 vs. 24 +/- 4 and 24 +/- 4 PMN/mm2, respectively; mean +/- SEM) and histological evidence of transmural myocardial infarction (100% vs. 47% and 53%, respectively) in electrocardiographically designated, expected infarct sites. In both saline- and ibuprofen-treated animals, there was extensive localization of C4, C3, and C5 in all infarct sites; in contrast, there was only C4 localization in the CVF-treated baboons. When expected infarct sites were assessed for creatine kinase content as an indicator of tissue injury, there was significantly less epicardial and endocardial creatine kinase depletion in the CVF-treated animals (31.7 +/- 5.6% and 39.3 +/- 4.8%) than in the saline-treated animals (54.1 +/- 5.4% and 59.0 +/- 4.7%; p = 0.012 and 0.011, respectively). The percent creatine kinase depletion in the ibuprofen-treated animals was intermediate between the two other groups. These results suggest that depletion of complement after coronary ligation has beneficial effects in reducing tissue injury that cannot be explained solely on the basis of reducing PMN infiltration into the ischemic myocardium.
Role of p38α Map Kinase in Type I Interferon Signaling (2004)

Multiple signaling pathways are activated during engagement of the Type I interferon (IFN) receptor to mediate biological responses, including the Jak-Stat and Rac1/p38 Map kinase signaling cascades. In the present study we sought to determine the functional relevance of the p38alpha isoform in IFN signaling, using cells from mouse embryos with targeted disruption of the p38alpha gene. Our data demonstrate that p38alpha activation is essential for Type I IFN-dependent transcriptional regulation via ISRE or GAS elements. On the other hand, the function of p38alpha is not required for IFN-dependent Ser727 or Tyr701 phosphorylation of Stat1 and does not impact on the formation of ISGF3 or SIF nuclear binding complexes. In efforts to identify downstream effectors of p38 that may mediate IFN-dependent transcriptional responses, we found that IFNalpha activates the kinase Msk1, a known regulator of histone phosphorylation and chromatin remodeling. In other studies, we demonstrate that Type I IFN-dependent activation of the kinases MapKapK-2 and MapKapK-3 is defective in the absence of p38alpha, while Type I IFN-dependent antiviral properties are decreased in cells with targeted disruption of the MapKapK-2 gene. Altogether, our data establish that the p38alpha Map kinase pathway regulates activation of downstream effectors that participate in the induction of IFN-dependent gene transcription, to mediate IFN-responses.
The Inhibitory Effect of Lidocaine on the Release of High Mobility Group Box 1 in Lipopolysaccharide-Stimulated Macrophages (2011)

Our data suggest that lidocaine functions as an antiinflammatory by inhibiting expression of HMGB1 mRNA, and translocating both HMGB1 and NF-κB from the nucleus to cytoplasm. The mechanism of these effects might be involved, at least partly, in the inhibition of the NF-κB signal pathway.
Screen-based trading in futures markets: recent developments and research propositions (2003)

Screen-based futures markets are gaining trading volumes at the expense of traditional open outcry floor markets. In comparison with open outcry trading-used on the Chicago Board of Trade (CBOT), the world largest future market-electronic markets offer enhanced transparency, and greater access to users, who can enter orders directly. Screen markets can also maintain strict time priorities among submitted orders, and can provide incentives for users to place competitive orders and enhance the price discovery process. We describe several new screen-based markets, and examine in detail the Cantor Financial Futures Exchange (CFFE), a screen market for Treasury futures contracts. The CFFE trading rules and order matching algorithms are shown to provide important incentives to place competitive quotes and supply liquidity. The design of an experimental economics study of the two alternative market structures-open outcry and a screen mechanism-is described.
Deriving cse-specific live forensics investigation procedures from FORZA (2007)

Performing live forensics investigation becomes a trend in digital forensics. Different vendors and software developer implement their own investigation procedures. By applying FORZA framework -- a digital forensics investigation framework, investigation requirement could be translated and formulated into criteria in applying appropriate forensics investigation requirement. Through this model, only necessary searching would be applied to live investigation process instead of simply passing all investigation process to live investigation unintentionally.
Prolonged Remissions of Cystic and Conglobate Acne with 13-cis-Retinoic Acid (1979)

Fourteen patients with treatment-resistant cystic and conglobate acne were treated for four months with oral 13-cis-retinoic acid, a synthetic isomer of naturally occurring all-trans-retinoic acid. The average dose was 2.0 mg per kilogram per day. Thirteen patients experienced complete clearing of their disease; the other had 75 per cent improvement, as determined by the number of acne nodules and cysts present before and after therapy. Prolonged remissions, currently lasting as long as 20 months after discontinuation of therapy, have been observed in all 14 patients. Clinical toxicity was limited to the skin and mucous membranes in most patients and was dose dependent and rapidly reversible upon discontinuation of therapy. The mechanism of action of 13-cis-retinoic acid in the therapy of acne probably involves a direct inhibitory effect of the drug on the sebaceous gland.
Proteomics‐based identification of α‐enolase as a tumor antigen in non‐small lung cancer (2007)

Autoantibodies against tumor antigens represent one type of biomarker that may be assayed in serum for detection of cancer and monitoring of disease progression. In the present study, we used a proteomics-based approach to identify novel tumor antigens in non-small cell lung cancer (NSCLC). By combining two-dimensional electrophoresis, western blotting, mass spectrometry and enzyme-linked immunosorbent assay technology, we detected autoantibodies against alpha-enolase in a subset of NSCLC patients' sera. When 'Mean OD(healthy control sera) + 3 SD(healthy control sera)' was used as the cut-off point, the prevalence of this autoantibody was 27.7% in patients with NSCLC (26 of 94), 1.7% in healthy control subjects (1 of 60), and not detectable in sera from 15 patients with small cell lung cancer, 18 patients with gastrointestinal cancer and nine patients with Mycobacterium avium complex infection of lung. Immunohistochemical staining showed that expression of alpha-enolase was increased in cancer tissues of NSCLC patients, and flow cytometric analysis confirmed the expression of alpha-enolase at the surface of cancer cells. The combined detection of autoantibodies against alpha-enolase, carcinoembryonic antigen and cytokeratin 19 fragment (CYFRA21-1) enhanced sensitivity for the diagnosis of NSCLC. Therefore, autoantibodies against alpha-enolase may constitute a promising biomarker for NSCLC.
Topoisomerase‐I, thymidylate synthase primary tumour expression and clinical efficacy of 5‐FU/CPT‐11 chemotherapy in advanced colorectal cancer patients (2004)

While several studies have reported that thymidylate synthase (TS) tumour expression can be a reliable predictive marker of clinical response to 5-Fluorouracil (5-FU) for advanced colorectal cancer patients, only a few studies that searched for predictive factors of irinotecan (CPT-11) clinical response are available. The aim of the present study has been to verify the predictive value of immunohistochemical topoisomerase-I (Topo-I) and TS primary tumour expression in a consecutive series of 62 advanced colorectal cancer patients that received a first line 5-FU/CPT-11 chemotherapy. TS and Topo-I immunostaining was observed in 76% and 43% of tumours, respectively, resulting in a significant relationship within each tumour (r=0.365, p<0.004). Patients with different TS tumour expression showed a similar percentage of Objective Clinical Response, OR (40% vs. 28% of OR in low and high TS-expressing tumours, respectively, p=ns); also, patients with different Topo-I tumour expression did not show a different probability of OR (39% vs. 29% of OR in high and low Topo-I expressing tumours, respectively; p=ns). The tumour expression of these 2 biomarkers also did not impact on time to progression and overall survival of patients. Furthermore, the combined analysis of TS and Topo-I tumour status did not permit to individualize subgroups of patients with different probability of OR. With multivariate analysis, only patient Performance Status significantly impacted on OS (Hazard ratio 4.87; p=0.02) of these patients. We can conclude that high TS tumour expression seems not to preclude a clinical activity for 5-FU/CPT-11 polichemotherapy in advanced colorectal cancer patients; furthermore, clinical response and prognosis of colorectal cancer patients treated with 5-FU/CPT-11 regimen do not differ in tumours with different TS or Topo-I expression.
Metabolic and health effects of isomeric fatty acids (2005)

Evidence is increasing that trans monounsaturated fatty acids from hydrogenated oils increase plasma markers of low-grade chronic inflammation. From epidemiological studies, however, it is not clear if effects of ruminant and industrial trans fatty acids on cardiovascular risk are different. Effects of CLA on body composition remain controversial and more research is needed before the widely available CLA supplements should be advocated as an adjunct to control body weight.
A Dynamic Three-Dimensional Network Visualization Program for Integration into CyberCIEGE and Other Network Visualization Scenarios (2007)

Detailed information and intellectual understanding of a network's topology and vulnerabilities is invaluable to better securing computer networks. Network protocol analyzers and intrusion detection systems can provide this additional information. In particular, game-based trainers, such as CyberCIEGE, have been shown to improve the level of training and understanding of network security professionals. This thesis' objective is to enhance these applications by developing NTAV3D, or, Network Topology and Attack Visualizer (Three Dimensional). NTAV3D is a tool that displays network topology, vulnerabilities, and attacks in an interactive, three-dimensional environment. This augments the design and game play of CyberCIEGE by increasing game player interaction and data display. Additionally, NTAV3D can be expanded to provide this capability to network analysis and intrusion detection tools. Furthermore, NTAV3D expands on ideas and results from related work of the best ways to visualize network topology, vulnerabilities, and attacks. NTAV3D was created using open-source software technologies including Xj3D, X3D, Java, and XML. It is also one of the first applications to be built with only the Xj3D toolkit. Therefore, the development process allowed evaluation of these technologies, resulting in recommendations for future improvements.
A Comparison of Text Retrieval Models (1992)

Many retrieval models have been proposed as the basis of text retrieval systems. The three main classes that have been investigated are the exact-match, vector space and probabilistic models. The retrieval effectiveness of strategies based on these models has been evaluated experimentally, but there has been little in the way of comparison in terms of their formal properties. In this paper we introduce a recent form of the probabilistic model based on inference networks, and show how the vector space and exact-match can be described in this framework. Differences between these models can be explained as differences in the estimation of probabilities, both in the initial search and during relevance feedback.
Lack of association of CFD polymorphisms with advanced age-related macular degeneration. (2010)

Our findings suggest that CFD may not play a major role in the genetic susceptibility to AMD because no association was found between the six SNPs analyzed in the CFD region and advanced AMD.
Enzymes: a practical introduction to structure, mechanism, and data analysis (2001)

A Brief History of Enzymology. Chemical Bonds and Reactions in Biochemistry. Structural Components of Enzymes. Protein-Ligand Binding Equilibria. Kinetics of Single-Substrate Enzyme Reactions. Chemical Mechanisms in Enzyme Catalysis. Experimental Measures of Enzyme Activity. Reversible Inhibitors. Tight Binding Inhibitors. Time-Dependent Inhibition. Enzyme Reactions with Multiple Substrates. Cooperativity in Enzyme Catalysis. Appendices. Index.
Cyclosporin Analogs Modified in the 3,7,8-Positions: Substituent Effects on Peptidylprolyl Isomerase Inhibition and Immunosuppressive Activity Are Nonadditive (1995)

Four analogs of cyclosporin A (CsA) were synthesized to determine if the biological activities of CsA analogs generated by multiple amino acid replacements are predictable from the effects on biological activity of analogs with single residue changes. CsA analogs [Phe7]CsA (8a), [D-MeAla3,Phe7]CsA (8b), [D-Ser8,Phe7]CsA (8c), and [D-MeAla3,Phe7,D-Ser8]CsA (8d) were designed by modification of positions 3, 7, and 8, which are adjacent to one effector region of the cyclophilin-bound CsA complex. The syntheses of CsA analogs 8a-d were carried out by suitable modifications of the reported strategy. Each analog was characterized by NMR in deuterated chloroform and DMSO solutions, and their biological activities as inhibitors of cis-trans-peptidyl prolyl isomerase (PPIase), inhibitors of proliferation in BDF1 mouse spleen cells stimulated with concanavalin A (Con A), and inhibitors of IL-2 release stimulated with PMA/ionomycin by Jurkat cells were determined. Incorporation of the phenylalanine residue in position 7 diminished activities 5-8-fold. Substitution at position 3 decreased activity nearly 2-fold, and substitution at position 8 did not lower activities. However, when all three modifications (D-MeAla3,Phe7, and D-Ser8) were incorporated into one molecule, the resulting analog, 8d, was found to bind more tightly to cyclophilin than CsA (Ki = 3 +/- 1.5 vs 6 +/- 2 nM) and to produce the full immunosuppressive effect in the other assay systems. Our structure-activity results show that combinations of substitutions that individually lower PPIase or immunosuppressive activity produce fully active analogs when combined in a single compound. These results suggest that other, multimodified CsA derivatives may be discovered that possess excellent or improved immunosuppressive activities even though they contain a substitution that otherwise reduces immunosuppressive activity.
One dimensional heterostructures and resonant tunneling in III-V nanowires (2004)

We use a bottom-up approach to grow epitaxially nucleated semiconductor nanowires from gold particles. Heterostructure barriers of InP are introduced inside InAs nanowires to form resonant tunneling diodes and single-electron transistors.