gebhart/patrepeval huggingface dataset:
Protein-protein interactions: methods for detection and analysis (1995)

The function and activity of a protein are often modulated by other proteins with which it interacts. This review is intended as a practical guide to the analysis of such protein-protein interactions. We discuss biochemical methods such as protein affinity chromatography, affinity blotting, coimmunoprecipitation, and cross-linking; molecular biological methods such as protein probing, the two-hybrid system, and phage display: and genetic methods such as the isolation of extragenic suppressors, synthetic mutants, and unlinked noncomplementing mutants. We next describe how binding affinities can be evaluated by techniques including protein affinity chromatography, sedimentation, gel filtration, fluorescence methods, solid-phase sampling of equilibrium solutions, and surface plasmon resonance. Finally, three examples of well-characterized domains involved in multiple protein-protein interactions are examined. The emphasis of the discussion is on variations in the approaches, concerns in evaluating the results, and advantages and disadvantages of the techniques.
The use of surface tension measurements in the design of antibody-based product formulations. (1991)

Many proteins in aqueous solution are susceptible to interfacial denaturation and precipitation during mechanical agitation. With the large number of protein parenteral products currently in research or clinical testing, it is important not only to understand this denaturation process but also to develop effective methods for stabilizing the products. Surfactants, such as Polysorbate 80 or sodium dodecyl sulfate (SDS), are frequently used to stabilize parenteral products. While it is a commonly accepted technique, little has been published about the precipitation and stabilization processes in general. We describe the stabilization of antibody products in solution by preferential adsorption of a water-soluble, non-ionic surfactant at the air-liquid interface. Data are presented from antibody and immunotoxin solution shake studies and surface tension measurements to support the utility of surface tension measurements in formulation design.
Impact of hydrogen on electrical levels and luminescence of dislocation network at the interface of hydrophilically bonded silicon wafers (2012)

Abstract The hydrogen penetration and its impact on electro‐physical properties of dislocation network (DN) at the interface of directly bonded silicon wafers located close to the surface of semiconductor are investigated. The evolution of spectra of deep level transient spectroscopy (DLTS) after low temperature reverse bias annealing (RBA) procedure was monitored. It is established that DN resists the penetration of hydrogen ions into the bulk of silicon wafer. The dependence of amount of penetrated hydrogen on of dislocation density in DN is obtained and the model of its explanation is suggested. It is demonstrated that the hydrogenation did not reduce the concentration of shallow dislocation‐related levels and that the amount of hydrogen introduced by wet chemical etching is sufficient to eliminate detrimental action of deep levels. (© 2012 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Autoimmunity and cancer - Beneficial relationships (1997)

Autoimmune diseases are the consequence of the immune system attack on the self. Autoimmunity, sometimes, is reflected through the production of autoantibodies to various self antigens leading to cellular malfunction or destruction. In the current study we employ such autoantibodies for the treatment of cancer originated from the respective normal cells. This concept is wide and entails many autoimmune disorders and diversity of malignant conditions. To illustrate the therapeutic and practical potential we depicted four examples: vitiligo and melanoma - vitiligo is considered dermatologic autoimmune disorder presented as depigmented skin areas. The destruction of the pigmented cells (melanocytes) is mediated by autoantibodies. We have purified these anti-melanocyte antibodies from patients with vitiligo and showed their cytotoxic effect towards malignant melanoma cells in vitro and in vivo; anti-phospholipid syndrome (APLS) and cancer-cancer cells differ from normal cells by the expression of phosphatydilserine (PS) on their outer membrane surface. We have used such anti-PS autoantibodies, derived from patients with APLS, as effective treatment for melanoma in a murine system; Autoimmune hemolytic anemia (AIHA) and hematological malignancies - in patients with AIHA, the red blood cells (RBC) destruction is mediated by binding of autoantibodies to RBC. We have shown the specific binding of these anti-RBC autoantibodies to RBC and to malignant cells of the erythroid lineage. Thus, these autoantibodies may have diagnostic/therapeutic potential for conditions such as erythroleukemia and polycythemia vera; anti-lymphocyte antibodies and lymphoproliferative diseases - in SLE and other systemic autoimmune conditions autoantibodies directed against lymphocytes can be found. These cytotoxic antibodies can be targeted against lymphocytes of lymphoproliferative diseases such as chronic lymphocytic leukemia, or lymphoma. The diversity of autoimmune diseases provides a great source for human preformed highly specific autoantibodies which can be used as an effective immunotherapy by themselves, for diagnostic purposes, as a cell specific carrier conjugated to other cytotoxic agents and in combined therapy in the combat against cancer.
Effect of the GABAAagonist gaboxadol on nocturnal sleep and hormone secretion in healthy elderly subjects (2001)

Aging is associated with a dramatic decrease in sleep intensity and continuity. The selective GABA(A) receptor agonist gaboxadol has been shown to increase non-REM sleep and the duration of the non-REM episodes in rats and sleep efficiency in young subjects and to enhance low-frequency activity in the electroencephalogram (EEG) within non-REM sleep in both rats and humans. In this double-blind, placebo-controlled study, we investigated the influence of an oral dose of 15 mg of gaboxadol on nocturnal sleep and hormone secretion (ACTH, cortisol, prolactin, growth hormone) in 10 healthy elderly subjects (6 women). Compared with placebo, gaboxadol did not affect endocrine activity but significantly reduced perceived sleep latency, elevated self-estimated total sleep time, and increased sleep efficiency by decreasing intermittent wakefulness and powerfully augmented low-frequency activity in the EEG within non-REM sleep. These findings indicate that gaboxadol is able to increase sleep consolidation and non-REM sleep intensity, without disrupting REM sleep, in elderly individuals and that these effects are not mediated by a modulation of hormone secretion.
Echocardiographic Modeling of Cardiac Dyssynchrony Before and During Multisite Stimulation: A Prospective Study (2003)

Multisite biventricular pacing therapy offers significant clinical improvement in some stimulated patients with electrocardiographic criteria of cardiac dyssynchrony. However, observational data increasingly suggest that patients suffering from congestive heart failure in presence of modest QRS widening may also derive benefit from cardiac resynchronization therapy (CRT), and that some patients can be significantly improved clinically after system implantation despite no apparent change in QRS width. This pilot study explored the value of an echocardiographic model to identify cardiac electromechanical dyssynchrony parameters (EDP) in candidates for CRT, and their potential correction after implantation. The study included 66 consecutive CRT recipients of CRT in NYHA functional class III or IV who had one or more atrioventricular, interventricular or intraventricular dyssynchrony criteria. An immediate improvement was observed in 85% of the population with a partial or total correction of their EDP. However, the modifications in EDP differed considerably between recipients of de novo CRT systems and patients with previously implanted standard pacing systems upgraded with the implantation of a left ventricular lead. EDP measurements appear to identify potential candidates for CRT, and to confirm the success of system implantation.
Heregulin β1 drives gefitinib-resistant growth and invasion in tamoxifen-resistant MCF-7 breast cancer cells (2007)

HRGbeta1 can overcome the inhibitory effects of gefitinib on cell growth and invasion in Tam-R cells through promotion of erbB3/erbB2 heterodimerization and activation of the phosphatidylinositol 3-kinase/AKT signalling pathway. This may have implications for the effectiveness of anti-EGFR therapies in breast cancer as HRGbeta1 is enriched in many EGFR-positive breast tumours.
A chiral stationary phase which affords unusually high levels of enantioselectivity (1991)

Abstract A chiral stationary phase (CSP) derived from N ‐(1‐naphthyl) leucine has been prepared. This CSP is conceptually similar to the CSP derived from N ‐(2‐naphthyl)alanine and was expected to separate the enantiomers of the same clientele of analytes as does the latter. The magnitudes of the separation factors observed on the two CSPs may differ markedly for a given analyte, the new CSP often affording much greater enantioselectivity.
Stadium norm and Douglas-Rachford splitting: a new approach to road design optimization (2014)

The basic optimization problem of road design is quite challenging due to a objective function that is the sum of nonsmooth functions and the presence of set constraints. In this paper, we model and solve this problem by employing the Douglas-Rachford splitting algorithm. This requires a careful study of new proximity operators related to minimizing area and to the stadium norm. We compare our algorithm to a state-of-the-art projection algorithm. Our numerical results illustrate the potential of this algorithm to significantly reduce cost in road design.
Helena e Iaiá Garcia: representações de práticas de leitura e configuraçãoes do leitorado oitocentista brasileiro no romance machadiano (2008)

Este artigo estuda as representações de atos de leitura presentes nos romances Helena e Iaiá Garcia, de Machado de Assis, interpretando-as como instrumentos capazes de configurar o leitorado brasileiro oitocentista. Para tanto, são analisadas comparativamente as cenas de leitura protagonizadas por D. Úrsula, Helena, Estela e Iaiá. São observados modos de ler “femininos”, que viabilizam a reflexão sobre o lugar da mulher nesse Brasil ainda patriarcal e já caminhando para o capitalismo. A argumentação se sustenta, fundamentando-se nas idéias de Wolfgang Iser, Marisa Lajolo, Regina Zilberman, entre outros. This article studies the representations of reading acts presented in the novels Helena e Iaiá Garcia, by Machado de Assis, by assuming that these representations are tools capable of configuring the 18th century Brazilian reader profile. In order to demonstrate this hypothesis, a comparative analysis is carried out - concerning the scenes that are performed by D. Úrsula, Helena, Estela and Iaiá. We have noted “feminine” modes of reading, which permits one to reflect on the role played by women in Brazil at a patriarchal society, going through capitalism. The whole argumentation is underpinned by theoretical developments of authors such as Wolfgang Iser, Marisa Lajolo, Regina Zilberman, among others.
Induction of HIF–1α in response to hypoxia is instantaneous (2001)

ABSTRACT Despite the pivotal role the hypoxia‐inducible factor‐1α (HIF‐1α) plays in physiological and pathological processes, little is known regarding the timeframe and mechanisms involved in its regulation. We determined the onset, accumulation, and degradation of HIF‐1α and a number of redox‐sensitive nuclear factors over a range of pathophysiological oxygen concentrations. Experiments were carried out on nonadherent human HeLaS3 cells placed in tonometers to achieve rapid equilibration between the cell suspension and the various hypoxic/reoxygenation conditions. Exposure to hypoxia for less than 2 min already revealed nuclear HIF‐1α protein induction on Western blots and HIF‐1 DNA binding in EMSAs. One hour after anoxic/hypoxic exposure, nuclear HIF‐1α proteins reached maximal levels, which were maintained for 4 h. Reoxygenation reduced HIF‐1 DNA binding within 2 min, and nuclear HIF‐1α protein levels within 4 to 8 min, down to a level below the detection limit within 32 min. Western blot analysis of the redox sensitive nuclear factors NF‐κB, c‐Fos, c‐Jun, Ref‐1, and thioredoxin showed no alteration in their nuclear levels in response to anoxia/hypoxia, but reoxygenation rapidly caused a transient increase in nuclear NF‐κB and thioredoxin protein levels. The instant initiation of HIF‐1α accumulation shown here limits the hypoxic signaling pathway to below 2 min.
Endocrine Response in Rabbits Immunized with Native versus Deglycosylated Porcine Zona Pellucida Antigens1 (1991)

Previous studies evaluating porcine zona pellucida antigens for immunocontraceptive purposes have in some cases revealed altered ovarian function in association with antibody response. This study was undertaken in an attempt to identify zona immunogens that do not cause adverse endocrine effects. To this end, we investigated the effects of highly purified preparations of native and deglycosylated pig zona pellucida antigens on ovarian function and immune response in the rabbit. Thirty female rabbits were immunized, 5 per group, with 100 micrograms each of either 1) SIZP, solubilized isolated zonae pellucidae; 2) ZP3, a purified porcine zona preparation containing the two principle glycoproteins, ZP3 alpha and ZP3 beta, endo-beta-galactosidase-digested ZP3 glycoproteins (approximately 30% deglycosylated) termed 3) ZP3 alpha/EBGD and 4) ZP3 beta/EBGD; and chemically deglycosylated ZP3 alpha and ZP3 beta (greater than or equal to 92% deglycosylated), termed 5) ZP3 alpha/DG and 6) ZP3 beta/DG. Rabbits injected with saline (n = 2) or Freund's adjuvant alone (n = 3) served as controls. Serum LH, FSH, estradiol, and progesterone were measured at 5-day intervals during seven 20-day cycles of hCG-induced pseudopregnancy over 42 wk. Anti-ZP3 titers, determined by RIA, developed in all treatment groups and correlated directly with carbohydrate content. Animals immunized with SIZP, ZP3, and ZP3 beta/EBGD showed a significant elevation of LH and FSH and a significant decline of peak progesterone levels by the fourth pseudopregnancy cycle. In contrast, animals immunized with ZP3 alpha/EBGD, ZP3 alpha/DG, and ZP3 beta/DG showed no significant elevations of gonadotropins and continued to display cyclic progesterone secretion in response to hCG.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative investigation of acoustic streaming in blood (2002)

Acoustic streaming may have practical utility in diagnostic medical ultrasound in distinguishing between stagnant blood and tissue as well as clotted and unclotted blood. This distinction can be difficult with conventional ultrasound but have high value in managing trauma patients with internal hemorrhage. Ultrasound energy applies a force to blood by momentum transfer, resulting in bulk streaming that is a function of the acoustic attenuation, sound speed, acoustic intensity, blood viscosity, and the boundary conditions posed by the geometry around the hematoma. A simple tubular model was studied analytically, by finite element simulation, and experimentally by in vitro measurement. The simulation agreed closely with measurements while the analytic solutions were found to be valid only for beam diameters approximating the diameter of the tubular channel. Experimentally, the acoustic streaming in blood decreased as the blood began to clot and the streaming flow was not detected in clotted blood. In contrast, the echogenicity of the same blood samples did not change appreciably from the unclotted to the clotted state for the stagnant blood studied. Streaming detection appears to offer a potential tool for improving hemorrhage diagnosis.
Percutaneous Left Atrial Appendage Transcatheter Occlusion to Prevent Stroke in High-Risk Patients With Atrial Fibrillation (2002)

Thus, transcatheter closure of the LAA is feasible in humans. This novel implant technology may be appropriate for patients with AF who are not suitable candidates for anticoagulation therapy. Further trials are needed to show the long-term safety and its efficacy in reducing stroke.
Induction of NKG2D ligands on human dendritic cells by TLR ligand stimulation and RNA virus infection (2007)

Monocyte-derived dendritic cells (mDCs) and NK cells are reciprocally activate via cytokines and cell-cell contact. Although seven human NKG2D ligands (NKG2DLs), UL16-binding proteins (ULBP) 1, 2, 3 and 4, retinoic acid early transcript 1G (RAET1G) and MHC class I-related chains A and B, have been reported, the differential distribution and roles of these ligands in the maturation of human mDCs have not been elucidated. In the present study, we produced polyclonal antibodies (pAbs) directed against human ULBP1, 2 and 3. All these ULBPs were detected on human mDCs when probed by the pAbs, although their expression profiles were different. We next investigated what kinds of Toll-like receptor agonists and RNA viruses [influenza virus, human respiratory syncytial virus (RSV), measles virus and hepatitis C virus (HCV)] induced the expression of NKG2DLs on mDCs. ULBP1 was up-regulated on mDCs in response to LPS or infection with RSV. The expression of ULBP2 was induced by LPS and poly I:C, indicating that the TIR-containing adapter molecule-1 (TIR domain-containing adaptor-inducing IFN) pathway is associated with ULBP2 induction. Although infection with HCV did not cause up-regulation of NKG2DLs, other RNA virus infections and poly I:C promoted expression of ULBP2 and RAET1G in an IFN-alpha/beta-independent manner. Finally, the over-expression of ULBP1 and 2 on mDCs facilitated NK cell proliferation and IFN-gamma production through a mDC-NK cell interaction in the presence of IL-2. Hence, the results reflect the important role of NKG2DLs on human mDCs in mDC-mediated NK cell activation.
HLA-G1 co-expression boosts the HLA class I-mediated NK lysis inhibition (2001)

It is now acknowledged that the pattern of HLA-G expression is not restricted to extravillous cytotrophoblast cells, as several studies described HLA-G in HLA class I+ cells, such as thymic epithelial cells, cytokine-activated monocytes and some tumors. In these situations, HLA-G may provide an additional inhibitory signal to escape from NK cell-mediated cytotoxicity. Accordingly, the aim of this study was to define the behavior of HLA-G once it is co-expressed into an HLA-A, -B, -C and -E+ cell line. For this purpose, HLA-G1 cDNA was transfected into an HLA class I+ melanoma cell line which was used as a target towards freshly isolated peripheral blood NK cells. Cytotoxic experiments using either anti-HLA-G1 or anti-HLA-G1 inhibitory receptor mAb show that HLA-G1 boosts the HLA class I-mediated inhibition of polyclonal NK cells through interaction with ILT-2, which appears as the major HLA-G1 inhibitory receptor involved. Nevertheless, HLA-G1 is also able to inhibit the cytolytic activity of an ILT-2- NK clone which otherwise expresses another HLA-G1 inhibitory receptor belonging to the KIR103 gene family. In order to more precisely define the relative role exerted by HLA-G1 versus -E on polyclonal NK cells, antibody-blocking assays were carried out using either anti-HLA class I or anti-CD94/NKG2A. Results demonstrate that in the absence of HLA-G1, the naturally expressed HLA class I-mediated NK inhibition is predominantly exerted by HLA-E through binding with CD94/NKG2A. In contrast, once HLA-G1 is expressed, it becomes the major NK inhibitory ligand.
Protective Role of Arginase in a Mouse Model of Colitis (2004)

Arginase is the endogenous inhibitor of inducible NO synthase (iNOS), because both enzymes use the same substrate, l-arginine (Arg). Importantly, arginase synthesizes ornithine, which is metabolized by the enzyme ornithine decarboxylase (ODC) to produce polyamines. We investigated the role of these enzymes in the Citrobacter rodentium model of colitis. Arginase I, iNOS, and ODC were induced in the colon during the infection, while arginase II was not up-regulated. l-Arg supplementation of wild-type mice or iNOS deletion significantly improved colitis, and l-Arg treatment of iNOS(-/-) mice led to an additive improvement. There was a significant induction of IFN-gamma, IL-1, and TNF-alpha mRNA expression in colitis tissues that was markedly attenuated with l-Arg treatment or iNOS deletion. Treatment with the arginase inhibitor S-(2-boronoethyl)-l-cysteine worsened colitis in both wild-type and iNOS(-/-) mice. Polyamine levels were increased in colitis tissues, and were further increased by l-Arg. In addition, in vivo inhibition of ODC with alpha-difluoromethylornithine also exacerbated the colitis. Taken together, these data indicate that arginase is protective in C. rodentium colitis by enhancing the generation of polyamines in addition to competitive inhibition of iNOS. Modulation of the balance of iNOS and arginase, and of the arginase-ODC metabolic pathway may represent a new strategy for regulating intestinal inflammation.
Roles of RuvC and RecG in Phage λ Red-Mediated Recombination (1999)

The recombination properties of Escherichia coli strains expressing the red genes of bacteriophage lambda and lacking recBCD function either by mutation or by expression of lambda gam were examined. The substrates for recombination were nonreplicating lambda chromosomes, introduced by infection; Red-mediated recombination was initiated by a double-strand break created by the action of a restriction endonuclease in the infected cell. In one type of experiment, two phages marked with restriction site polymorphisms were crossed. Efficient formation of recombinant DNA molecules was observed in ruvC+ recG+, ruvC recG+, ruvC+ recG, and ruvC recG hosts. In a second type of experiment, a 1-kb nonhomology was inserted between the double-strand break and the donor chromosome's restriction site marker. In this case, recombinant formation was found to be partially dependent upon ruvC function, especially in a recG mutant background. In a third type of experiment, the recombining partners were the host cell chromosome and a 4-kb linear DNA fragment containing the cat gene, with flanking lac sequences, released from the infecting phage chromosome by restriction enzyme cleavage in the cell; the formation of chloramphenicol-resistant bacterial progeny was measured. Dependence on RuvC varied considerably among the three types of cross. However, in all cases, the frequency of Red-mediated recombination was higher in recG than in recG+. These observations favor models in which RecG tends to push invading 3'-ended strands back out of recombination intermediates.
News Keyword Extraction for Topic Tracking (2008)

This paper presents a keyword extraction technique that can be used for tracking topics over time. In our work, keywords are a set of significant words in an article that gives high-level description of its contents to readers. Identifying keywords from a large amount of on-line news data is very useful in that it can produce a short summary of news articles. As on-line text documents rapidly increase in size with the growth of WWW, keyword extraction has become a basis of several text mining applications such as search engine, text categorization, summarization, and topic detection. Manual keyword extraction is an extremely difficult and time consuming task; in fact, it is almost impossible to extract keywords manually in case of news articles published in a single day due to their volume. For a rapid use of keywords, we need to establish an automated process that extracts keywords from news articles. We propose an unsupervised keyword extraction technique that includes several variants of the conventional TF-IDF model with reasonable heuristics.