gebhart/patrepeval huggingface dataset:
Critical binding site amino acids of anti-Z-DNA single chain Fv molecules. Role of heavy and light chain CDR3 and relationship to autoantibody activity. (1994)

Bacterial expression of single chain variable fragment (scFv) domains was used to assess Ag-binding contributions of specific regions and residues in a mouse mAb to Z-DNA (AbZ22). A variant scFv (Z3-3) that did not bind Z-DNA had the Z22 light chain but differed from the Z22 heavy chain at four complimentarity determining region 3 (CDR3), one FR4 and five VH segment residues. Gene segment swapping and site-directed mutagenesis indicated that the major contribution of the Z22 heavy chain is its CDR3. A scFv with the CDR3H-FR4H of Ab Z22 and the VH segment of Z3-3 had the same selective high affinity Z-DNA binding as Z22. Some Z-DNA binding was retained even when the CDR3H-FR4H of Ab Z22 was combined with a VH segment that shared only 44% sequence identity with Z22. Directed mutations indicated further that residues N99 and S98 in heavy chain CDR3 and F96 in light chain CDR3 were particularly important for Ag binding. Certain substitutions in CDR3H converted the highly selective Z22 Fv into a polyreactive Fv with autoantibody-like binding to B-DNA and denatured DNA. In a graphic molecular model, heavy chain N99 protrudes from the CDR3 loop at the base of the Ag-binding groove, and the light chain F96 is barely exposed on the base of this groove; the light chain F96 may be important in heavy chain-light chain association. Autoantibody and immunization-induced Ab to nucleic acid can be built on a very similar framework and differ by a small number of amino acid CDR3H residues.
Effect of Low-Level Laser Radiation on Some Rheological Factors in Human Blood: An in Vitro Study (2000)

This study has shown that LLLR, even though used at low doses and low power densities, produced some changes of the rheological factors of the blood, as follows: a revitalizing and regenerating effect on mitosis stimulation and a nondamaging and biostimulating effect on the cell membrane (by keeping unmodified MCV, MCH, and MCHC). In 3 cases out of 22, hemolysis (complete or partially) occurred, but we are not yet sure whether this was caused by laser exposure or by certain environmental physical factors.
αNAC Requires an Interaction With c-Jun to Exert its Transcriptional Coactivation (2002)

alphaNAC is a transcriptional coactivator known to interact with the N-terminal activation domain of the c-Jun transcription factor. In this article, we describe the identification of the c-Jun interaction domain within the alphaNAC protein. Deletion analysis of alphaNAC indicated that the c-Jun binding site was located in the middle part of the protein, between residues 89 and 129. The deletion of the C-terminal end of alphaNAC, including the c-Jun interacting domain, induced a nuclear translocation of the mutated coactivator. Despite its presence in the nucleus, this deletion mutant did not retain the capacity to coactivate an AP-1 response. These results demonstrate that the interaction between alphaNAC and c-Jun was necessary for the potentiation of theAP-1 transcriptional activity. These data are consistent with a mechanism by which alphaNAC acts as a coactivator for c-Jun-dependent transcription by interacting with the c-Jun N-terminal activation domain.
High-power air-clad large-mode-area photonic crystal fiber laser (2003)

We report on a 2.3 m long air-clad ytterbium-doped large-mode area photonic crystal fiber laser generating up to 80 W output power with a slope efficiency of 78%. Single transverse mode operation is achieved with a mode-field area of 350 µm2. No thermo-optical limitations are observed at the extracted ~35W/m, there fore such fibers allow scaling to even higher powers.
Reversible inhibition of lysine specific demethylase 1 is a novel anti-tumor strategy for poorly differentiated endometrial carcinoma (2014)

Our findings demonstrate the anti-cancer properties of the LSD1 inhibitor HCI2509 on poorly differentiated endometrial carcinoma cell lines, AN3CA and KLE. HCI2509 showed single-agent efficacy in orthotopic xenograft studies. Continued studies are needed to preclinically validate LSD1 inhibition as a therapeutic strategy for endometrial carcinoma.
Expression of Cholesteryl Ester Transfer Protein in Mice Promotes Macrophage Reverse Cholesterol Transport (2007)

The present results demonstrate that CETP expression promotes macrophage RCT in mice, that this effect is dependent on the low-density lipoprotein receptor, and that CETP expression restores to normal the impaired RCT in mice deficient in scavenger receptor class B, type I.
Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease (1997)

Little is known about the potential for engraftment of autologous hematopoietic stem cells in human adults not subjected to myeloablative conditioning regimens. Five adult patients with the p47(phox) deficiency form of chronic granulomatous disease received intravenous infusions of autologous CD34(+) peripheral blood stem cells (PBSCs) that had been transduced ex vivo with a recombinant retrovirus encoding normal p47(phox). Although marrow conditioning was not given, functionally corrected granulocytes were detectable in peripheral blood of all five patients. Peak correction occurred 3-6 weeks after infusion and ranged from 0.004 to 0.05% of total peripheral blood granulocytes. Corrected cells were detectable for as long as 6 months after infusion in some individuals. Thus, prolonged engraftment of autologous PBSCs and continued expression of the transduced gene can occur in adults without conditioning. This trial also piloted the use of animal protein-free medium and a blood-bank-compatible closed system of gas-permeable plastic containers for culture and transduction of the PBSCs. These features enhance the safety of PBSCs directed gene therapy.
Three‐dimensional fabrication of engineered bone with human bio‐derived bone scaffolds in a rotating wall vessel bioreactor (2007)

Bone tissue engineering has emerged as a promising strategy in the effort to regenerate and repair diseased or damaged bone. The bioreactor, within which engineered bone tissue is cultured, plays a key role in the development of engineered bone graphs. In this work, the potentials of the rotating wall vessel bioreactor (RWVB) and the human bio-derived bone scaffolds (BDBS) for 3D bone culture are evaluated. The osteoblasts isolated from the cranium of neonatal Sprague-Dawley (SD) rat of 3 days old were expanded firstly with microcarrier suspension culture in a RWVB. After the assessment of the biological functions of the expanded cells by histomorphometry, the cells were seeded at 2 x 10(6) and 1 x 10(6) cells/mL, respectively, onto the 3D human BDBS and cultured for 3 weeks in the RWVB. The cells metabolism and nutrient concentration were monitored in the whole culture processes. The structure of the harvested bone tissues was observed with optical microscope and scanning electron microscope (SEM). The biological properties of the engineered bone were detected by alkaline phosphatase (ALP) expression and alizarin red staining to visualize the newly formed bone. Acridine orange/ethidium bromide (AO/EB) double fluorescence staining was used to analyze the cell activity. For a comparative study, cell seeded constructs were also cultured in static conditions. The results indicate that the bone grafts cultured in RWVB with two different seeded cell densities grew well, and the cell number expanded in RWVB was five times as that in T-flask and spinner flask. There were significantly more collagen fibers mineralized nodules and new osteoid tissue formed than those in T-flask and spinner flask. It also demonstrated that with the stress stimulation inside the fluid in the RWVB, the ALP expression could be increased; the formation of mineralized nodules can be accelerated.
cDNA Cloning and Tissue Distribution of a Rat Ubiquitin Carboxyl-Terminal Hydrolase PGP9.51 (1992)

We have isolated a cDNA clone encoding ubiquitin carboxyl-terminal hydrolase PGP9.5 from a rat brain cDNA library and examined the tissue distribution. The primary structure of the cDNA consists of 856 nucleotides including the entire coding region for 223 amino acids, and the calculated molecular mass is 24,782 Da. The rat PGP9.5 is strikingly homologous to the human PGP9.5, 75.2% of nucleic acids and 95.1% of amino acids being identical. The mRNA of PGP9.5 is most abundant in the rat brain and to a lesser degree in the testis. In other peripheral tissues we tested, the mRNA was undetectable. Western blotting using an anti-rat PGP9.5 antibody revealed the parallel distribution of mRNA and protein in various brain regions and testis. The availability of the rat PGP9.5 clone provides a new approach to examine the function of PGP9.5 and the role that it plays in the pathology of neurodegenerative diseases.
Comprehensive Approach to Modeling and Simulation of Photovoltaic Arrays (2009)

This paper proposes a method of modeling and simulation of photovoltaic arrays. The main objective is to find the parameters of the nonlinear <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I-V</i> equation by adjusting the curve at three points: open circuit, maximum power, and short circuit. Given these three points, which are provided by all commercial array data sheets, the method finds the best <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I-V</i> equation for the single-diode photovoltaic (PV) model including the effect of the series and parallel resistances, and warranties that the maximum power of the model matches with the maximum power of the real array. With the parameters of the adjusted <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I-V</i> equation, one can build a PV circuit model with any circuit simulator by using basic math blocks. The modeling method and the proposed circuit model are useful for power electronics designers who need a simple, fast, accurate, and easy-to-use modeling method for using in simulations of PV systems. In the first pages, the reader will find a tutorial on PV devices and will understand the parameters that compose the single-diode PV model. The modeling method is then introduced and presented in details. The model is validated with experimental data of commercial PV arrays.
Physiological Diversity of Nicotinic Acetylcholine Receptors Expressed by Vertebrate Neurons (1995)

The last decade has revealed an astounding degree of physiological and st ruct ural divers it y in neurot ransmitteract ivated receptors. In part icular, mo­ lecular st udies of the acet ylcholine-gated recept ors in vert ebrate muscle cells and Torpedo elect rocyt es gave birt h to a new era of research on a relat ed s ubfamil y of nicotinic r eceptors ( nA Ch Rs) expressed by centr al and periph­ eral neurons. Th is review focuses on the nA ChR s ubt ypes expressed by neurons , viewed mainly from a ph ys iological pers pect ive. It is intended t o complement s everal excellent recent reviews o n muscle-type A ChRs (42, 45, 56) and on the anatomi cal dist ri buti on, bi ochemistry, and molecular bi ology of neuronal nAChRs (35, 61, 66, 95). The work s ummarized in this review has helped answer a long-standing q uest ion: How can t he wellknown behavioral, cognit ive, and addict ive eff ects of ni cotine be reconci led with the paucity of evidence for CNS s ynapses where t he t rans mission is mediat ed by nicot inic recept ors? The ident ificat ion of a large family of neuronal nA ChR s ubu nit genes and an array of funct ionally dist inct nA ChRs has given a bas is for t he divers e effects of nicot ine. P erhaps
Hepatic Atypical Protein Kinase C: An Inherited Survival-Longevity Gene that Now Fuels Insulin-Resistant Syndromes of Obesity, the Metabolic Syndrome and Type 2 Diabetes Mellitus (2014)

This review focuses on how insulin signals to metabolic processes in health, why this signaling is frequently deranged in Western/Westernized societies, how these derangements lead to, or abet development of, insulin-resistant states of obesity, the metabolic syndrome and type 2 diabetes mellitus, and what our options are for restoring insulin signaling, and glucose/lipid homeostasis. A central theme in this review is that excessive hepatic activity of an archetypal protein kinase enzyme, "atypical" protein kinase C (aPKC), plays a critically important role in the development of impaired glucose metabolism, systemic insulin resistance, and excessive hepatic production of glucose, lipids and proinflammatory factors that underlie clinical problems of glucose intolerance, obesity, hepatosteatosis, hyperlipidemia, and, ultimately, type 2 diabetes. The review suggests that normally inherited genes, in particular, the aPKC isoforms, that were important for survival and longevity in times of food scarcity are now liabilities in times of over-nutrition. Fortunately, new knowledge of insulin signaling mechanisms and how an aberration of excessive hepatic aPKC activation is induced by over-nutrition puts us in a position to target this aberration by diet and/or by specific inhibitors of hepatic aPKC.
The receptor-binding sequence of urokinase. A biological function for the growth-factor module of proteases. (1987)

Previous studies have shown that the region of human urokinase-type plasminogen activator (uPA) responsible for receptor binding resides in the amino-terminal fragment (ATF, residues 1-135) (Stoppelli, M.P., Corti, A., Soffientini, A., Cassani, G., Blasi, F., and Assoian, R.K. (1985) Proc. Natl. Acad. Sci. U.S. A. 82, 4939-4943). The area within ATF responsible for specific receptor binding has now been identified by the ability of different synthetic peptides corresponding to different regions of the amino terminus of uPA to inhibit receptor binding of 125I-labeled ATF. A peptide corresponding to human [Ala19]uPA-(12-32) resulted in 50% inhibition of ATF binding at 100 nM. Peptides uPA-(18-32) and [Ala13]uPA-(9-20) inhibit at 100 and 2000 microM, respectively. The human peptide uPA-(1-14) and the mouse peptide [Ala20]uPA-(13-33) have no effect on ATF receptor binding. This region of uPA is referred to as the growth factor module since it shares partial amino acid sequence homology (residues 14-33) to epidermal growth factor (EGF). Furthermore, this region of EGF is responsible for binding of EGF to its receptor (Komoriya, A. Hortsch, M., Meyers, C., Smith, M., Kanety, H., and Schlessinger, J. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1351-1355). However, EGF does not inhibit ATF receptor binding. Comparison of the sequences responsible for receptor binding of uPA and EGF indicate that the region of highest homology is between residues 13-19 and 14-20 of human uPA and EGF, respectively. In addition, there is a conservation of the spacings of four cysteines in this module whereas there is no homology between residues 20-30 and 21-33 of uPA and EGF. Thus, residues 20-30 of uPA apparently confer receptor binding specificity, and residues 13-19 provide the proper conformation to the adjacent binding region.
Treatment with gamma‐interferon triggers the onset of collagen arthritis in mice (1988)

We investigated the effect of gamma-interferon (gamma-IFN) on the development of type II collagen (CII)-induced arthritis. DBA/1 mice were immunized with rat CII and 16 days later, were treated with subcutaneous injections of recombinant rat gamma-IFN into the right paws twice a week. Compared with controls, the gamma-IFN-treated mice developed arthritis with a higher frequency and severity. Immunohistochemical analysis of gamma-IFN-treated paws from CII-immunized mice revealed an increase in the numbers of class II antigen-expressing cells and an infiltration of CD4+ lymphocyte-like cells. The auto-antibody response toward CII was suppressed by gamma-IFN treatment. The findings implicate gamma-IFN in a role that triggers arthritis by enhancing local inflammatory processes in the joints, or possibly, by permitting homing of T cells to the joints.
The energetic cost of domain reorientation in maltose-binding protein as studied by NMR and fluorescence spectroscopy (2003)

Maltose-binding protein (MBP) is a two-domain protein that undergoes a ligand-mediated conformational rearrangement from an "open" to a "closed" structure on binding to maltooligosaccharides. To characterize the energy landscape associated with this transition, we have generated five variants of MBP with mutations located in the hinge region of the molecule. Residual dipolar couplings, measured in the presence of a weak alignment medium, have been used to establish that the average structures of the mutant proteins are related to each other by domain rotation about an invariant axis, with the rotation angle varying from 5 degrees to 28 degrees. Additionally, the domain orientations observed in the wild-type apo and ligand-bound (maltose, maltotriose, etc.) structures are related through a rotation of 35 degrees about the same axis. Remarkably, the free energy of unfolding, measured by equilibrium denaturation experiments and monitored by fluorescence spectroscopy, shows a linear correlation with the rotation angle, with the stability of the (apo)protein decreasing with domain closure by 212 +/- 16 cal mol-1 per degree of rotation. The apparent binding energy for maltose also shows a similar correlation with the interdomain angle, suggesting that the mutations, as they relate to binding, affect predominantly the ligand-free structure. The linearity of the energy change is interpreted in terms of an increase in the extent of hydrophobic surface that becomes solvent accessible on closure. The combination of structural, stability, and binding data allows separation of the energetics of domain reorientation from ligand binding. This work presents a near quantitative structure-energy-binding relationship for a series of mutants of MBP, illustrating the power of combined studies involving protein engineering and solution NMR spectroscopy.
An Approach for Secure Software Installation (2002)

We present an approach that addresses the problem of securing software configurations from the security-relevant actions of poorly built/faulty installation packages. Our approach is based on apolicy-based control of the package manager’s actions and is customizable for site-specific policies. We discuss an implementation of this approach in the context of the Linux operating system for the Red Hat Package manager (RPM).
Pathophysiology of the blood-brain barrier (1990)

Content Headings: List of Participants. Preface. The Erik K. Fernstrom Foundation. Acknowledgements. Section I. Current Concepts of the Blood-Brain Barrier (papers 1-8). Section II. Pathophysiology of Barrier Mechanisms (papers 9-16). Section III. Therapeutic Role of Barrier Modifications (papers 17-22). Section IV. Blood-Brain Barrier in Neurotoxicology (papers 23-27). Section V. The Blood-Brain Barrier in the Pathophysiology of Cerebrovascular Lesions (papers 28-34). Section VI . Afferent and Efferent Pathways from the Brain to the Immune System (papers 35-41). Section VII . Antigen Presentation in the Central Nervous System (papers 42-44). Section VIII . Immunocytotherapy in the Brain (papers 45-47). Section IX . Transplantation in the Central Nervous System (papers 48-53). Full contents list available on request from the Publisher. Imprint Amsterdam
flp‐1, the first representative of a new pilin gene subfamily, is required for non‐specific adherence of Actinobacillus actinomycetemcomitans (2001)

Actinobacillus actinomycetemcomitans, a Gram-negative bacterium responsible for localized juvenile periodontitis and other infections such as endocarditis, produces long fibrils of bundled pili that are believed to mediate non-specific, tenacious adherence to surfaces. Previous investigations have implicated an abundant, small ( approximately 6.5 kDa), fibril-associated protein (Flp/Fap) as the primary fibril subunit. Here, we report studies on fibril structure and on the function and evolution of Flp. High-resolution electron microscopy of adherent clinical strain CU1000N revealed long bundles of 5- to 7-nm-diameter pili, whose subunits appear to be arranged in a helical array similar to that observed for type IV pili in other bacteria. Fibrils were found to be associated with the bacterial cell surface and smaller structures thought to be membrane vesicles. A modified version of the CU1000N Flp1 polypeptide with the T7-TAG epitope fused to its C-terminus was expressed in the wild-type strain, and the presence of the modified Flp1 in fibrils was confirmed by immunogold electron microscopy with monoclonal antibody to T7-TAG. To determine the importance of Flp1 in fibril formation and cell adherence, we used transposon IS903phikan to isolate insertion mutations in the flp-1 gene (formerly designated flp). Mutants with insertions early in flp-1 fail to produce fibrils and do not adhere to surfaces. Both fibril production and adherence were restored by cloned flp-1 in trans, thus providing the first evidence that flp-1 is required for fibril formation and tight, non-specific adherence. One mutant was found to have an insertion near the 3' end of flp-1 that results in the expression of a truncated and altered C-terminus of Flp1. This mutant produced short, unbundled pili, and its adherence to surfaces was significantly less than that of wild-type bacteria. These findings and related observations with the Flp1-T7-TAG protein indicate that the C-terminus of Flp1 is important for the bundling and adherence properties of pili. Extensive sequence comparisons and phylogenetic analysis of 61 predicted prepilin genes of bacteria revealed flp-1 to be a member of a novel and widespread subfamily of type IV prepilin genes. Thus, Flp pili are likely to be expressed by diverse bacterial species. Furthermore, we found that it is common for bacterial genomes to contain multiple alleles of flp-like genes, including the open reading frame (flp-2, previously designated orfA) immediately downstream of flp-1 in A. actinomycetemcomitans. The duplication and divergence of flp genes in bacteria may be important to the diversification of the colonization properties of these organisms.
Chiral synthesis via organoboranes. 28. Reaction of .alpha.-chiral organyldichloroboranes with organyl azides providing a synthesis of secondary amines with exceptionally high enantiomeric purities (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral synthesis via organoboranes. 28. Reaction of .alpha.-chiral organyldichloroboranes with organyl azides providing a synthesis of secondary amines with exceptionally high enantiomeric puritiesHerbert C. Brown, Ashok M. Salunkhe, and Bakthan SingaramCite this: J. Org. Chem. 1991, 56, 3, 1170–1175Publication Date (Print):February 1, 1991Publication History Published online1 May 2002Published inissue 1 February 1991https://doi.org/10.1021/jo00003a046RIGHTS & PERMISSIONSArticle Views531Altmetric-Citations56LEARN 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 InReddit PDF (798 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts