gebhart/patrepeval huggingface dataset:
Independent modes of transcriptional activation by the p50 and p65 subunits of NF-kappa B. (1992)

Recombinant subunits of the transcription factor NF-kappa B, p50 and p65, were analyzed both for binding to various kappa B motifs and in vitro activation. The subunits preferentially form a heterodimer that activates transcription. Although p50 and p65 bind DNA individually as homodimers and are structurally related, their activation mechanisms are distinct. p65 activates transcription by its unique carboxy-terminal activation domain. (p50)2 displays higher affinity DNA binding than (p65)2 for many distinct kappa B motifs and provides strong transcriptional activation only when adopting a chymotrypsin-resistant conformation induced by certain kappa B motifs but not others. Thus, (p50)2 acts as a positive regulator in vitro, consistent with its isolation as a putative constitutive regulator of MHC class I genes. Both subunits of NF-kappa B, therefore, contribute independently to provide regulation at given kappa B motifs.
Antisense-mediated silencing of a gene encoding a major ryegrass pollen allergen (1999)

Type 1 allergic reactions, such as hay fever and allergic asthma, triggered by grass pollen allergens are a global health problem that affects approximately 20% of the population in cool, temperate climates. Ryegrass is the dominant source of allergens because of its prodigious production of airborne pollen. Lol p 5 is the major allergenic protein of ryegrass pollen, judging from the fact that almost all of the individuals allergic to grass pollen show presence of serum IgE antibodies against this protein. Moreover, nearly two-thirds of the IgE reactivity of ryegrass pollen has been attributed to this protein. Therefore, it can be expected that down-regulation of Lol p 5 production can significantly reduce the allergic potential of ryegrass pollen. Here, we report down-regulation of Lol p 5 with an antisense construct targeted to the Lol p 5 gene in ryegrass. The expression of antisense RNA was regulated by a pollen-specific promoter. Immunoblot analysis of proteins with allergen-specific antibodies did not detect Lol p 5 in the transgenic pollen. The transgenic pollen showed remarkably reduced allergenicity as reflected by low IgE-binding capacity of pollen extract as compared with that of control pollen. The transgenic ryegrass plants in which Lol p 5 gene expression is perturbed showed normal fertile pollen development, indicating that genetic engineering of hypoallergenic grass plants is possible.
Monoclonal Antibodies in Immunoscintigraphy (1989)

This book examines the role of immunoscintigraphy using radiolabeled monoclonal antibodies in the imaging of malignant recurrences, infarcts, and thrombi, as well as its real contribution to diagnostic strategy in comparison with conventional methods such as the use of ultrasonography, computed tomography, and magnetic resonance imaging.
Limits on the performance of RF-over-fiber links and their impact on device design (2006)

This paper is divided into two major parts. Following a brief introduction that establishes some definitions and assumptions, Section II updates our earlier study on the limits of the RF performance of optical links. Section III reviews progress since our 1997 review paper in the development of devices enabling link performance closer to these limits, including (but not limited to): 1) cascade lasers that permit broad-band direct modulation links with gain >0 dB; 2) injection-locked edge- and surface-emitting lasers at 1300 and 1550 nm with modulation frequency responses as great as 40 GHz; 3) modulators with improved performance, especially electroabsorption modulators that now have switching voltages as low as 0.36 V, or handle optical powers as great as 60 mW, or have bandwidths as great as 50 GHz (but not all three of these in one device yet); and 4) high-speed photodetectors with high saturation currents, e.g., a 20-GHz device with a saturation current of 90 mA and a 55-GHz device with saturation at 50 mA. We conclude in Section IV by summarizing the component developments necessary for higher performance RF-over-fiber links, i.e.: 1) semiconductor lasers (for direct modulation) that have higher slope efficiency and bandwidth and lower relative intensity noise (RIN) at reasonable bias current levels; 2) continuous wave (CW) lasers (for external modulation) with higher fiber-coupled power and lower RIN; 3) higher frequency lower loss external modulators with more linear transfer functions and lower V/sub /spl pi// that can withstand larger CW optical powers; and 4) photodetectors with higher responsivity and bandwidth that respond linearly even when illuminated by greater average optical powers.
Synthesis, DNA-binding properties, and antitumor activity of novel distamycin derivatives [Erratum to document cited in CA110(19):173740j] (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis, DNA-binding properties, and antitumor activity of novel distamycin derivatives [Erratum to document cited in CA110(19):173740j]Federico Maria Arcamone, Fabio Animati, Brunella Barbieri, Emanuela Configliacchi, Roberto D'Alessio, Cristina Geroni, Fernando Carlo Giuliani, Ettore Lazzari, Milena Menozzi, and Cite this: J. Med. Chem. 1989, 32, 12, 2583Publication Date (Print):December 1, 1989Publication History Published online1 May 2002Published inissue 1 December 1989https://pubs.acs.org/doi/10.1021/jm00132a022https://doi.org/10.1021/jm00132a022research-articleACS PublicationsRequest reuse permissionsArticle Views29Altmetric-Citations-LEARN 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
Binding characteristics and affinity labeling of protein constituents of the human IM-9 lymphoblast receptor for substance P. (1986)

The neuropeptide substance P (SP) stimulates human T-lymphocyte function in vitro. Human blood T-lymphocytes and cultured human IM-9 B-lymphoblasts express 7,000-10,000 and 25,000-30,000 substance P receptors per cell, respectively. The specific binding of 125I-SP is retained in IM-9 lymphoblast membranes solubilized in 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS) at a detergent-to-protein ratio of 1.0. In addition, specific and reversible SP binding to soluble IM-9 cell membrane proteins is demonstrated by gel filtration. The saturation of binding of 125I-SP to both intact and solubilized IM-9 cell membranes attained a steady state after 40-50 min at 4 degrees C. Scatchard analysis of the concentration dependence of 125I-SP binding to IM-9 cell membranes revealed a KD of 0.87 +/- 0.8 nM (mean +/- S.D., n = 4), which is similar to that observed in intact cells, and a density of receptors of 21 +/- 3 fmol/mg of membrane protein (mean +/- S.D.). Binding of 125I-SP to solubilized membranes demonstrated a KD of 0.75 +/- 0.33 nM (mean +/- S.D., n = 3) and a density of receptors of 3.7 +/- 1.5 fmol/mg of membrane protein (mean +/- S.D., n = 3). Affinity cross-linking of 125I-SP by disuccinimidyl suberate to intact IM-9 cells and membranes revealed specifically labeled proteins of Mr 58,000 and 33,000 in cells, and 58,000, 33,000, and 16,000 in membranes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under both reducing and nonreducing conditions. Competitive effects of substituent peptides of SP on cross-linking and 125I-SP binding to membranes demonstrated that the SP receptor recognized the carboxyl-terminal domain of the peptide. Membranes from cells preincubated in vitro for 12 h at 37 degrees C with 10(-8) M SP demonstrated a decrease in SP receptor density to 13 +/- 2 fmol/mg (mean +/- S.D., n = 2), and a parallel diminution in the specific labeling of membrane proteins of Mr 58,000 and 33,000. These observations suggest that solubilization in CHAPS preserves the binding characteristics of the IM-9 lymphoblast receptor for SP, and that affinity cross-linking techniques identify by sodium dodecyl sulfate-polyacrylamide gel electrophoresis membrane proteins that are specifically labeled by SP.
Identification of a Linear Heparin Binding Domain for Human Respiratory Syncytial Virus Attachment Glycoprotein G (1999)

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in infants and young children worldwide. Infection is mediated, in part, by an initial interaction between attachment protein (G) and a highly sulfated heparin-like glycosaminoglycan (Gag) located on the cell surface. Synthetic overlapping peptides derived from consensus sequences of the G protein ectodomain from both RSV subgroups A and B were tested by heparin-agarose affinity chromatography for their abilities to bind heparin. This evaluation identified a single linear heparin binding domain (HBD) for RSV subgroup A (184A-->T198) and B (183K-->K197). The binding of these peptides to Vero cells was inhibited by heparin. Peptide binding to two CHO cell mutants (pgsD-677 and pgsA-745) deficient in heparan sulfate or total Gag synthesis was decreased 50% versus the parental cell line, CHO-K1, and decreased an average of 87% in the presence of heparin. The RSV-G HBD peptides were also able to inhibit homologous and heterologous virus infectivity of Vero cells. These results indicate that the sequence 184A/183K-->198T/K197 for RSV subgroups A and B, respectively, defines an important determinant of RSV-G interactions with heparin.
Cholesteryl ester accumulation in macrophages resulting from receptor-mediated uptake and degradation of hypercholesterolemic canine beta-very low density lipoproteins. (1980)

The synthesis and accumulation of cholesteryl esters by monolayers of mouse peritoneal macrophages was stimulated 20- to 160-fold by incubation with beta-migrating very low density lipoproteins (beta-VLDL, density less than 1.006 g/ml) isolated from the plasma of cholesterol-fed dogs. Three other cholesterol-rich lipoprotein fractions obtained from the plasma of the same hypercholesterolemic dogs, including low density lipoprotein (LDL), cholesterol-induced high density lipoprotein (HDLc), and apo-E HDLc, had little to no stimulatory effect. Plasma VLDL (density less than 1.006 g/ml) from normal dogs did not increase cholesteryl ester formation in macrophages. The enhancement in cholesteryl ester synthesis and accumulation by hypercholesterolemic canine beta-VLDL was due to the presence of a high affinity binding site on the macrophage cell surface that mediated the uptake and lysosomal degradation of the beta-VLDL. Competition studies with fucoidin and dextran sulfate indicated that the receptor for canine beta-VLDL was different from that previously described for human acetylated low density lipoprotein (acetyl-LDL). Prior incubation of macrophage monolayers with either unlabeled canine beta-VLDL or human acetyl-LDL, both of which raised the cellular content of cholesteryl esters, reduced the ability of the cells to degrade 125I-labeled beta-VLDL, suggesting that the receptor for beta-VLDL is subject to regulation. The current findings indicate: 1) that macrophages possess a high affinity receptor that recognizes one of the four cholesterol-rich lipoproteins present in the plasma of cholesterol-fed dogs, beta-VLDL, and 2) that the receptor-mediated ingestion of beta-VLDL leads to cholesteryl ester deposition in these cells.
Review series on helminths, immune modulation and the hygiene hypothesis: Immunity against helminths and immunological phenomena in modern human populations: coevolutionary legacies? (2008)

Although the molecules and cells involved in triggering immune responses against parasitic worms (helminths) remain enigmatic, research has continued to implicate expansions of T-helper type 2 (Th2) cells and regulatory T-helper (T(reg)) cells as a characteristic response to these organisms. An intimate association has also emerged between Th2 responses and wound-healing functions. As helminth infections in humans are associated with a strong Th2/T(reg) immunoregulatory footprint (often termed a 'modified Th2' response), plausible links have been made to increased susceptibility to microbial pathogens in helminth-infected populations in the tropics and to the breakdowns in immunological control (allergy and autoimmunity) that are increasing in frequency in helminth-free developed countries. Removal of helminths and their anti-inflammatory influence may also have hazards for populations exposed to infectious agents, such as malaria and influenza, whose worst effects are mediated by excessive inflammatory reactions. The patterns seen in the control of helminth immunity are discussed from an evolutionary perspective. Whilst an inability to correctly regulate the immune system in the absence of helminth infection might seem highly counter-adaptive, the very ancient and pervasive relationship between vertebrates and helminths supports a view that immunological control networks have been selected to function within the context of a modified Th2 environment. The absence of immunoregulatory stimuli from helminths may therefore uncover maladaptations that were not previously exposed to selection.
Identification of novel antimitotic agents acting at the tubulin level by computer-assisted evaluation of differential cytotoxicity data. (1992)

Data generated in the new National Cancer Institute drug evaluation program, which are based on inhibition of cell growth in 60 human tumor cell lines, were probed with nine known antimitotic agents using the COMPARE algorithm. Cytotoxicity data were available on approximately 7000 compounds at the time of the analysis, and, based on the criteria used, 82 compounds were selected as positive by the computer search. Nine were the probe compounds themselves, and 41 were analogues of known antimitotic agents. Among the remaining 32 compounds there were 19 distinct chemical species. Agents in ten of these groups (containing 20 compounds) were effective inhibitors of in vitro tubulin polymerization and caused the mitotic arrest of cells grown in culture. Two compounds were related natural products binding in the Vinca domain of tubulin, and the others were synthetic agents which interfered with colchicine binding. The remaining 12 agents (one natural product, the remainder synthetic) fell into several groups: two compounds were weak inhibitors of tubulin polymerization, inhibited colchicine binding, and caused mitotic arrest; one compound weakly inhibited tubulin polymerization but did not cause an increase in the number of cells arrested in mitosis; two compounds caused mitotic arrest at micromolar concentrations, but thus far no in vitro interaction with tubulin has been observed; the remainder neither inhibited tubulin polymerization nor caused a rise in the number of cultured cells arrested in mitosis. Tubulin-dependent GTP hydrolysis was stimulated or inhibited by all agents which inhibited tubulin polymerization with the exception of one compound. The analysis of differential cytotoxicity data thus appears to have great promise for the identification of new antimitotic agents with antineoplastic potential.
Adaptive server selection for large scale interactive online games (2004)

In this paper, we present a novel distributed algorithm that dynamically selects game servers for a group of game clients participating in large scale interactive online games. The goal of server selection is to minimize server resource usage while satisfying the real-time delay constraint. We develop a synchronization delay model for interactive games and formulate the server selection problem, and prove that the considered problem is NP-hard. The proposed algorithm, called zoom-in-zoom-out, is adaptive to session dynamics (e.g. clients join and leave) and lets the clients select appropriate servers in a distributed manner such that the number of servers used by the game session is minimized. Using simulation, we present the performance of the proposed algorithm and show that it is simple yet effective in achieving its design goal. In particular, we show that the performance of our algorithm is comparable to that of a greedy selection algorithm, which requires global information and excessive computation.
Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues (1995)

High titre replication of human cytomegalovirus (HCMV) in cell culture is restricted to primary human fibroblasts. During acute infection in vivo, HCMV nucleic acids and antigens have been found in various organs. Using only morphological criteria, inconsistent data have been reported about the cell types that can be infected by HCMV. In particular, the role of fibroblasts in organ infections has remained unclear. To define accurately the target cells of HCMV in vivo, tissue sections from lung and gastrointestinal tract of patients suffering from acute HCMV infection were investigated using immunohistochemical double-labelling analyses. Monoclonal antibodies with defined specificity against immediate early (IE), early (E) and late (L) viral antigens and antibodies directed against cell marker proteins were employed to identify infected cells. The results demonstrated that a broad spectrum of cells was infected by HCMV in vivo. Consistent with their susceptibility in culture, fibroblasts formed a major population of HCMV-infected cells. In contrast, haemopoietic cells were only infrequently stained with virus-specific antibodies. Fibroblasts, epithelial cells, endothelial cells, smooth muscle cells and macrophages appeared to be permissive for HCMV replication. Contrary to this, polymorphonuclear cells showed only IE gene expression, indicating that these cells were abortively infected. The analysis of the distribution of infected cells in tissue supported the hypothesis that endothelial cells and monocytes/macrophages may play a crucial role in the haematogenous spread of HCMV; in contrast, fibroblasts, smooth muscle cells and epithelial cells may form the cell populations important for the multiplication and spread of the virus in infected tissues.
Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications. (1992)

The substrate specificities of human aldose reductase and aldehyde reductase toward trioses, triose phosphates, and related three-carbon aldehydes and ketones were evaluated. Both enzymes are able to catalyze the NADPH-dependent reduction of all of the substrates used. Aldose reductase shows more discrimination among substrates than does aldehyde reductase and is generally the more efficient catalyst. The best substrate for aldose reductase is methylglyoxal (kcat = 142 min-1, kcat/Km = 1.8 x 10(7) M-1 min-1), a toxic 2-oxo-aldehyde that is produced nonenzymatically from triose phosphates and enzymatically from acetone/acetol metabolism. D- and L-glyceraldehyde and D- and L-lactaldehyde are also good substrates for aldose reductase. The aldose reductase-catalyzed reduction of methylglyoxal produces 95% acetol, 5% D-lactaldehyde. Further reduction of acetol produces only L-1,2-propanediol. Acetol and propanediol are two products that accumulate in uncontrolled diabetes. Both acetol and methylglyoxal were compared with glucose for their abilities to produce covalent modification of albumin. All three of these carbonyl compounds reacted with albumin to produce modified proteins with new absorption and emission bands that are spectrally similar. Both methylglyoxal and acetol are much more reactive than glucose. A new integrative model of diabetic complications is proposed that combines the aldose reductase/polyol pathway theory and the nonenzymatic glycation theory except that emphasis is placed both on methylglyoxal/acetol metabolism and on glucose metabolism.
Effect of Cardiopulmonary Bypass and Heparin on Plasma Levels of Lp(a) and Apo(a) Fragments (1999)

Fragments of apolipoprotein(a) [apo(a)], the distinctive glycoprotein of lipoprotein(a) [Lp(a)], are present in human plasma and urine and have been implicated in the development of atherosclerosis. The mechanism responsible for the generation of apo(a) fragments in vivo is poorly understood. In this study, we examined the plasma levels of Lp(a) and apo(a) fragments [or free apo(a)] and urinary apo(a) in 15 subjects who underwent cardiac surgery necessitating cardiopulmonary bypass. We also measured the plasma concentration and activity of polymorphonuclear elastase, an Lp(a)-cleaving enzyme in vitro, and plasma levels of C-reactive protein. Despite a marked activation of polymorphonuclear cells and a pronounced inflammatory response, as documented by an 8-fold and a 35-fold increase in plasma levels of polymorphonuclear elastase and C-reactive protein, respectively, the proportion of plasma free apo(a) to Lp(a) and urinary excretion of apo(a) remained unchanged over a 7-day period after surgery, and polymorphonuclear elastase activity remained undetectable in plasma. No fragmentation of apo(a) was observed ex vivo in plasma samples collected before and after surgery. These data indicate that in this model, apo(a) is not fragmented in plasma and are consistent with the hypothesis that apo(a) fragments result from a constitutively active tissue mechanism that is not modified by cardiac surgery with cardiopulmonary bypass.
Dissolved Oxygen Levels Alter Gene Expression and Antigen Profiles in Borrelia burgdorferi (2004)

The Lyme disease spirochete, Borrelia burgdorferi, encounters many environmental signals as it cycles between the arthropod vector and mammalian hosts, including temperature, pH, and other host factors. To test the possibility that dissolved oxygen modulates gene expression in B. burgdorferi, spirochetes were exposed to differential levels of dissolved oxygen, and distinct alterations were observed at both the transcriptional and translational levels. Specifically NapA, a Dps/Dpr homologue involved in the oxidative stress response in other bacteria, was reduced when B. burgdorferi was grown under oxygen-limiting conditions. In contrast, several immunoreactive proteins were altered when tested with infection-derived sera from different hosts. Specifically, OspC, DbpA, and VlsE were synthesized at greater levels when cells were grown in limiting oxygen, whereas VraA was reduced. The levels of oxygen in the medium did not affect OspA production. Real-time reverse transcription-PCR analysis of RNA isolated from infectious isolates of strains B31 and cN40 indicated that the expression of ospC, dbpA, and vlsE increased while napA expression decreased under dissolved-oxygen-limiting conditions, whereas flaB was not affected. The reverse transcription-PCR results corroborated the immunoblot analyses and indicated that the increase in OspC, DbpA, and VlsE was due to regulation at the transcriptional level of the genes encoding these antigens. These results indicate that dissolved oxygen modulates gene expression in B. burgdorferi and imply that the redox environment may be an additional regulatory cue that spirochetes exploit to adapt to the disparate niches that they occupy in nature.