gebhart/patrepeval huggingface dataset:
Exchange of Viral Promoter/Enhancer Elements with Heterologous Regulatory Sequences Generates Targeted Hybrid Long Terminal Repeat Vectors for Gene Therapy of Melanoma (1998)

To generate transcriptionally targeted vectors, tissue-specific elements of the human tyrosinase promoter were exchanged with corresponding viral elements in the Moloney murine leukemia virus long terminal repeat (LTR). From these experiments, a vesicular stomatitis virus type G pseudotyped, hybrid LTR vector that contained three tyrosinase enhancer elements and gave high-level, tightly tissue-specific expression at high titers (3 x 10(7) CFU/ml) was constructed.
Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival (2003)

Multiple myeloma (MM) is a progressive disease that is thought to result from multiple genetic insults to the precursor plasma cell that ultimately affords the tumor cell with proliferative potential despite its differentiated phenotype and resistance to undergoing apoptosis. Altered expression of antiapoptotic factors as well as growth factors have been described in a significant number of patients. However, the key regulatory elements that control myeloma development and progression remain largely undefined. Because of the knowledge that B-lymphocyte stimulator (BLyS), a tumor necrosis factor (TNF) family member shown to be critical for maintenance of normal B-cell development and homeostasis, promotes the survival of malignant B cells, we began a coordinated study of BLyS and its receptors in MM. All MM cells studied expressed one or more of 3 known receptors (B-cell maturation antigen [BCMA], transmembrane activator and CAML interactor [TACI], and B-cell activating factor receptor [BAFF-R]) for BLyS; however, the pattern of expression was variable. Additionally, we provide evidence that BLyS can modulate the proliferative capacity and survival of MM cells. Finally, we provide evidence that BLyS is expressed by MM cells and is present in the bone marrow of patients with MM. Expression of BCMA, TACI, and BAFF-R by MM taken together with the ability of BLyS to support MM cell growth and survival has exciting implications because they may be potential therapeutic targets.
Suppression of the Induction of Alpha, Beta, and Gamma Interferons by the NS1 and NS2 Proteins of Human Respiratory Syncytial Virus in Human Epithelial Cells and Macrophages (2004)

Wild-type human respiratory syncytial virus (HRSV) is a poor inducer of alpha/beta interferons (IFN-alpha/beta). However, recombinant HRSV lacking the NS1 and NS2 genes (Delta NS1/2) induced high levels of IFN-alpha and -beta in human pulmonary epithelial cells (A549) as well as in macrophages derived from primary human peripheral blood monocytes. Results with NS1 and NS2 single- and double-gene-deletion viruses indicated that the two proteins function independently as well as coordinately to achieve the full inhibitory effect, with NS1 having a greater independent role. The relative contributions of the individual NS proteins were the converse of that recently described for bovine RSV (J. F. Valarcher, J. Furze, S. Wyld, R. Cook, K. K. Conzelmann, and G. Taylor, J. Virol. 77:8426-8439, 2003). This pattern of inhibition by HRSV NS1 and NS2 also extended to the newly described antiviral cytokines IFN-lambda 1, -2 and -3.
Vision-based technique for bolt-loosening detection in wind turbine tower (2015)

In this study, a novel vision-based bolt-loosening monitoring technique is proposed for bolted joints connecting tubular steel segments of the wind turbine tower (WTT) structure. Firstly, a bolt-loosening detection algorithm based on image processing techniques is developed. The algorithm consists of five steps: image acquisition, segmentation of each nut, line detection of each nut, nut angle estimation, and bolt-loosening detection. Secondly, experimental tests are conducted on a lab-scale bolted joint model under various bolt-loosening scenarios. The bolted joint model, which is consisted of a ring flange and 32 sets of bolt and nut, is used for simulating the real bolted joint connecting steel tower segments in the WTT. Finally, the feasibility of the proposed vision-based technique is evaluated by bolt-loosening monitoring in the lab-scale bolted joint model.
Safety and Efficacy of Sildenafil Citrate for the Treatment of Female Sexual Arousal Disorder: A Double-Blind, Placebo Controlled Study (2003)

Sildenafil was effective and well tolerated in postmenopausal women with FSAD without concomitant HSDD or contributory emotional, relationship or historical abuse issues. All patients had protocol specified estradiol and free testosterone concentrations or were receiving estrogen and/or androgen replacement therapy.
Relevant use of Klotho in FGF19 subfamily signaling system in vivo (2010)

Alpha-Klotho (alpha-Kl) and its homolog, beta-Klotho (beta-Kl) are key regulators of mineral homeostasis and bile acid/cholesterol metabolism, respectively. FGF15/ humanFGF19, FGF21, and FGF23, members of the FGF19 subfamily, are believed to act as circulating metabolic regulators. Analyses of functional interactions between alpha- and beta-Kl and FGF19 factors in wild-type, alpha-kl(-/-), and beta-kl(-/-) mice revealed a comprehensive regulatory scheme of mineral homeostasis involving the mutually regulated positive/negative feedback actions of alpha-Kl, FGF23, and 1,25(OH)(2)D and an analogous regulatory network composed of beta-Kl, FGF15/humanFGF19, and bile acids that regulate bile acid/cholesterol metabolism. Contrary to in vitro data, beta-Kl is not essential for FGF21 signaling in adipose tissues in vivo, because (i) FGF21 signals are transduced in the absence of beta-Kl, (ii) FGF21 could not be precipitated by beta-Kl, and (iii) essential phenotypes in Fgf21(-/-) mice (decreased expressions of Hsl and Atgl in WAT) were not replicated in beta-kl(-/-) mice. These findings suggest the existence of Klotho-independent FGF21 signaling pathway(s) where undefined cofactors are involved. One-to-one functional interactions such as alpha-Klotho/FGF23, beta-Klotho/FGF15 (humanFGF19), and undefined cofactor/FGF21 would result in tissue-specific signal transduction of the FGF19 subfamily.
Regulation of Immune Responses by mTOR (2012)

mTOR is an evolutionarily conserved serine/threonine kinase that plays a central role in integrating environmental cues in the form of growth factors, amino acids, and energy. In the study of the immune system, mTOR is emerging as a critical regulator of immune function because of its role in sensing and integrating cues from the immune microenvironment. With the greater appreciation of cellular metabolism as an important regulator of immune cell function, mTOR is proving to be a vital link between immune function and metabolism. In this review, we discuss the ability of mTOR to direct the adaptive immune response. Specifically, we focus on the role of mTOR in promoting differentiation, activation, and function in T cells, B cells, and antigen-presenting cells.
Time course and dose response of relaxin-mediated renal vasodilation, hyperfiltration, and changes in plasma osmolality in conscious rats (2003)

The pregnancy hormone relaxin elicits renal vasodilation, hyperfiltration, and osmoregulatory changes when chronically administered to conscious, nonpregnant rats. The objective in this study was to determine the dose response and time course of hormone action, as well as the time required for recovery on stopping its administration. The threshold dose of recombinant human relaxin (rhRLX) for renal vasodilation and reduction in plasma osmolality was 0.15 microg/h when given by subcutaneous osmotic minipump for 2 days (an infusion rate that achieved circulating levels of approximately 6 ng/ml). The peak response was observed during the 0.4 microg/h infusion rate (serum rhRLX of approximately 11 ng/ml), which was comparable to our previous work using a 4.0 microg/h (serum rhRLX of approximately 20 ng/ml). In contrast, a dose of 40 microg/h was ineffective (serum rhRLX of approximately 80 ng/ml). When 4.0 microg/h rhRLX was administered by osmotic minipump for shorter periods (</=24 h), renal circulatory and osmoregulatory changes were observed by </=6 h. After removal of the osmotic minipump, these changes persisted for at least 12 h, but they were fully restored by 24 h. Even briefer administration of 4.0 microg/h rhRLX by intravenous infusion showed an onset of action in the kidney by 1-2 h. In contrast, the 40 microg/h dose of rhRLX elicited minimal effects, and comparable to our earlier report, 4.0 microg/h purified porcine relaxin was also relatively ineffective during short-term intravenous administration. In conclusion, the effect of relaxin on the renal circulation and osmoregulation is biphasic, insofar as high doses are relatively inactive, and the onset of action is more rapid than previously believed. These findings may be important to consider when evaluating relaxin in the treatment of renal disease.
Glycosaminoglycan Sulfation Requirements for Respiratory Syncytial Virus Infection (2000)

Glycosaminoglycans (GAGs) on the surface of cultured cells are important in the first step of efficient respiratory syncytial virus (RSV) infection. We evaluated the importance of sulfation, the major biosynthetic modification of GAGs, using an improved recombinant green fluorescent protein-expressing RSV (rgRSV) to assay infection. Pretreatment of HEp-2 cells with 50 mM sodium chlorate, a selective inhibitor of sulfation, for 48 h prior to inoculation reduced the efficiency of rgRSV infection to 40%. Infection of a CHO mutant cell line deficient in N-sulfation was three times less efficient than infection of the parental CHO cell line, indicating that N-sulfation is important. In contrast, infection of a cell line deficient in 2-O-sulfation was as efficient as infection of the parental cell line, indicating that 2-O-sulfation is not required for RSV infection. Incubating RSV with the purified soluble heparin, the prototype GAG, before inoculation had previously been shown to neutralize its infectivity. Here we tested chemically modified heparin chains that lack their N-, C6-O-, or C2-O-sulfate groups. Only heparin chains lacking the N-sulfate group lost the ability to neutralize infection, confirming that N-sulfation, but not C6-O- or C2-O-sulfation, is important for RSV infection. Analysis of heparin fragments identified the 10-saccharide chain as the minimum size that can neutralize RSV infectivity. Taken together, these results show that, while sulfate modification is important for the ability of GAGs to mediate RSV infection, only certain sulfate groups are required. This specificity indicates that the role of cell surface GAGs in RSV infection is not based on a simple charge interaction between the virus and sulfate groups but instead involves a specific GAG structural configuration that includes N-sulfate and a minimum of 10 saccharide subunits. These elements, in addition to iduronic acid demonstrated previously (L. K. Hallak, P. L. Collins, W. Knudson, and M. E. Peeples, Virology 271:264-275, 2000), partially define cell surface molecules important for RSV infection of cultured cells.
Design and Optimization of Networks With Dynamic Routing (1981)

The growth of electronic switching systems and the high-capacity interoffice signaling network provide an opportunity to extend telephone network routing rules beyond the conventional hierarchy. Network models are described that illustrate the savings inherent in designing networks for dynamic, nonhierarchical routing. An algorithm for engineering such networks is discussed, and the comparative advantages of various path-routing and progressive-routing techniques are illustrated. A particularly simple implementation of dynamic routing called two-link dynamic routing with crankback is discussed and is shown to yield benefits comparable to much more complicated routing schemes. The efficient solution of embedded linear programming (LP) routing problems is an essential ingredient for the practicality of the design algorithm We introduce an efficient heuristic optimization method for solution of the LP routing problems, which greatly improves computational speed with minimal loss of accuracy. We also project computational requirements for a 200-node design problem, which is the estimated size of the intercity Bell System dynamic routing network in the 1990s.
A low-cost data-glove for Human computer interaction based on ink-jet printed sensors and ZigBee networks (2010)

In this paper, a data-glove based on new kind of sensors is presented as an alternative to expensive devices. These sensors were realized using a conductive polymer (PEDOT:PSS) thin film printed on glossy photo paper. To demonstrate the printed sensors, we constructed a data glove using such sensors and developed software for real-time hand tracking. Wireless networks based on low-cost ZigBee technology were used to transfer data from the glove to a computer. This data-glove is very useful in many contexts such as telerobotics, rehabilitation and HCI applications.
Immunological effects of interleukin 12 administered by bolus intravenous injection to patients with cancer. (1999)

The immunological effects of recombinant human interleukin 12 (rhIL-12) administration were examined during the conduct of a Phase I clinical trial. Forty patients with advanced cancer received bolus i.v. injections of rhIL-12 in doses ranging between 3 and 1000 ng/kg. Dose-dependent increases in serum IFN-gamma levels were seen during rhIL-12 therapy. Significant lymphopenia was observed 24 h after single i.v. injections of rhIL-12 at each dose level. The degree of lymphopenia was dose dependent, and a plateau effect was seen with rhIL-12 doses of 100 ng/kg and higher. Lymphocyte counts reached nadir levels at approximately 10 h after rhIL-12 injection and returned to baseline within 14 days postinjection. Rebound lymphocytosis, as seen after interleukin 2 therapy, was not observed after recovery from rhIL-12-induced lymphopenia. rhIL-12-induced lymphopenia involved all major lymphocyte subsets, although natural killer (NK) cell numbers were the most profoundly affected, and CD4 T-cell numbers were the least affected. CD2, LFA-1, and CD56 were transiently up-regulated on the surface of NK cells exposed to rhIL-12 in vivo. Peripheral blood mononuclear cells obtained from cancer patients before rhIL-12 therapy exhibited defective NK cell cytotoxicity and T-cell-proliferative responses. Peripheral blood mononuclear cells obtained after lymphocyte recovery following the administration of a single 500 ng/kg dose of rhIL-12 displayed augmented NK cell cytolytic activity in four of four patients tested and enhanced T-cell proliferation in three of four patients tested. These studies confirm that doses of rhIL-12 resulting in significant immunological activity can be administered with acceptable toxicity to cancer patients. Furthermore, rhIL-12 therapy can reverse defects in NK cell and T-cell function that are associated with advanced cancer in humans.
Sodium Channels and Neuropathic Pain (2004)

Although it has long been known that sodium channels play an important role in the generation of abnormal neuronal activity and neuropathic pain, it is only recently that we have begun to understand the subtypes of sodium channels which are particularly important in neuropathic pain. Many of the identified subtypes of sodium channels are localized in dorsal root ganglion (DRG) neurons. Based on their sensitivity to tetrodotoxin (TTX), these sodium channels are classified as TTX-sensitive (TTXs) or TTX-resistant (TTXr) subtypes. In in vitro electrophysiological experiments, ectopic discharges arising from DRG neurons with injured axons are blocked by TTX at doses that are too low to block TTXr subtypes. Furthermore, the same low doses of TTX applied to the DRG of the injured segment in neuropathic rats significantly reduce pain behaviours. These data suggest that TTXs subtypes of sodium channels are playing an important role in the generation of both ectopic discharges and neuropathic pain. Analysis of mRNA of the TTXs subtypes of sodium channels in the DRG after spinal nerve ligation showed that Nav1.3 (Type III) and Nax (NaG) are the only two subtypes that are up-regulated, suggesting their potentially important role in ectopic discharge and neuropathic pain generation.
Single base polymorphism in the human Tumour Necrosis Factor alpha (TNFα) gene detectable by Ncol restriction of PCR product (1992)

Journal Article Single base polymorphism in the human Tumour Necrosis Factor alpha (TNFα) gene detectable by Ncol restriction of PCR product Get access A.G. Wilson, A.G. Wilson * Section of Molecular Medicine, Department of Medicine and Pharmacology, University of SheffieldRoyal Hallamshire Hospital, Sheffield S10 2JF, UK *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar F.S. di Giovine, F.S. di Giovine Section of Molecular Medicine, Department of Medicine and Pharmacology, University of SheffieldRoyal Hallamshire Hospital, Sheffield S10 2JF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar A.I.F. Blakemore, A.I.F. Blakemore Section of Molecular Medicine, Department of Medicine and Pharmacology, University of SheffieldRoyal Hallamshire Hospital, Sheffield S10 2JF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar G.W. Duff G.W. Duff Section of Molecular Medicine, Department of Medicine and Pharmacology, University of SheffieldRoyal Hallamshire Hospital, Sheffield S10 2JF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 1, Issue 5, August 1992, Page 353, https://doi.org/10.1093/hmg/1.5.353 Published: 01 August 1992
Applications of Higher-Order Mixed Organocuprates to Organic Synthesis (1987)

Recent developments in the chemistry of higher-order cyanocuprates are discussed, including the appearance and use of several new reagents prepared from copper(I) cyanide (CuCN) or copper(I) thiocyanate (CuSCN) and two equivalents of various organometallics. Numerous applications to synthetic problems in natural products chemistry are also described. 1. Introduction 2. New Synthetic Methodology 2.1. R2Cu(CN)Li2/CO 2.1.1. RCu(CN)Li/CO 2.2. (R3Si)2Cu(CN)Li2 2.3. RTRRCu(CN)Li2 2.3.1. Effects of Lewis Acids 2.4. RTRRCu(CN)LiM 2.4.1. RTRRCu(CN)Li[(n-C4H9)4N] 2.4.2. RTRRCu(CN)LiMgX 2.5. R2Cu(SCN)Li2 3. Uses of Higher-Order Cyanocuprates in Synthesis 3.1. Applications to Natural Products Total Synthesis 3.1.1. Epoxide Openings 3.1.2. Other Displacement Reactions 3.1.3. Conjugate Additions 3.1.4. 1,2-Additions 4. Concluding Remarks
Identification of sesquiterpene hydrocarbons by gas phase analytical methods (1999)

Current techniques are described and demonstrated for the isolation and structural elucidation of sesquiterpene hydrocarbons, on the basis of enantioselective capillary gas chromatography, with cyclodextrin derivatives as chiral stationary phases and chemical microreactions for correlation of unknown sesquiterpenes with compounds of known constitution and absolute configuration. Copyright © 1999 John Wiley & Sons, Ltd.
Calorimetric and spectroscopic studies of the interaction of Manduca sexta apolipophorin III with zwitterionic, anionic, and nonionic lipids (1993)

The nature of the interaction of apolipophorin III (apoLp-III) from the insect Manduca sexta with a variety of zwitterionic and anionic phospholipids and with several nonionic glycolipids was investigated by differential scanning calorimetry (DSC) and 31P-NMR spectroscopy. Monoglucosyldiacylglycerol, phosphatidylethanolamine, and phosphatidic acid (pH 7.2) appear to exhibit the weakest interaction with apoLp-III. DSC studies revealed that the gel/liquid-crystalline phase transition of these lipids is little affected by the binding of apoLp-III. Diglucosyldiacylglycerol, phosphatidylcholine (PC), phosphatidylserine, and phosphatidic acid (pH congruent to 8.8) seem to exhibit somewhat stronger interactions with apoLp-III. The binding of apoLp-III to these lipids induces the formation of lipid domains which melt less cooperatively and at higher temperatures than do the pure lipid dispersions, while having little effect on the melting enthalpy of lipid hydrocarbon chains. Phosphatidylglycerol (PG) and phosphatidic acid (pH > 9.3) appear to exhibit the strongest interactions with apoLp-III. The binding of apoLp-III to these lipids severely disrupts their bilayer structure, resulting in marked reductions in the cooperativity and enthalpy of the gel/liquid-crystalline phase transition of the lipids. Studies of binary mixtures of PC and PG indicate that such bilayer-disrupting interactions only occur in the presence of nonphysiologically high concentrations of PG. The binding of apoLp-III to binary mixtures of diacylglycerol and zwitterionic phospholipid has little effect on the chain-melting or the bilayer/nonbilayer phase transitions of these lipids, but it appears to promote the retention of water at the surface of the lipid aggregate. Our results indicate that the binding of apoLp-III to lipid bilayers is mediated primarily through polar and/or ionic interactions at the lipid bilayer surface. Our results also suggest that the interaction of apoLp-III with lipid bilayers promotes the hydration of their surfaces, a property which is consistent with the proposed in vivo functions of this protein.
Complex-frequency leaky mode computations using PML boundary layers for dielectric resonant structures (2003)

Perfectly matched layers are used for finite-difference computation of complex-frequency leaky modes of resonant dielectric structures in cylindrical and Cartesian coordinates. Examples of dielectric-halfspace-perturbed 3D rings and 2D round, square and coupled resonators are given.
Effect of age on therapeutic outcome in advanced diffuse histiocytic lymphoma: the Southwest Oncology Group experience. (1986)

To study the influence of chronologic age on treatment outcome in patients with advanced, diffuse large-cell (histiocytic) lymphoma (DHL), we reviewed the results of two recent Southwest Oncology Group (SWOG) clinical trials. From 1974 to 1982, members entered 307 eligible patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without bleomycin, and CHOP with or without immunotherapy using BCG, levamisole, or both. Complete response (CR) rates declined progressively with advancing age: 65% in those under 40, 60% in the 40 to 54 age group, 55% in the 55 to 64 age group, and 37% in those 65 and older (P = .001). Likewise, survival decreased significantly in older patients: medians were 101 +, 52, 34, and 16 months, respectively (P less than .001). Treatment guidelines included an initial dose reduction of 50% for patients aged 65 or older and for younger patients with bone marrow compromise. Despite protocol specifications, 23 of 81 patients aged 65 or older received initial full-dose therapy. When these patients were compared with younger patients on whom full-dose chemotherapy was started, survival curves, but not CR rates, were still significantly different. There were no significant differences in duration of CR or frequency of treatment complications. These data suggest that older age is associated with a worse prognosis in advanced DHL. Moreover, the initial dose reduction for patients aged 65 or older may have contributed to their inferior outcomes.
Weak Magnetic Fields as a Novel Therapeutic Modality in Parkinson's Disease (1992)

AbstractMen who have excessive faith in their theories or ideas are not only ill prepared for making discoveries; they also make very poor observations. Claude Bernard (1813–1878)
Investigating the utility of combining Φ29 whole genome amplification and highly multiplexed single nucleotide polymorphism BeadArray™ genotyping (2004)

We conclude that the BeadArray technology successfully produces high quality genotyping data from MDA product. The combination of these technologies improves the feasibility and efficiency of mapping common disease susceptibility genes despite limited stocks of gDNA samples.