gebhart/patrepeval huggingface dataset:
Reconsideration of the catalytic center and mechanism of mammalian paraoxonase/arylesterase. (1995)

For three decades, mammalian paraoxonase (A-esterase, aromatic esterase, arylesterase; PON, EC 3.1.8.1) has been thought to be a cysteine esterase demonstrating structural and mechanistic homologies with the serine esterases (cholinesterases and carboxyesterases). Human, mouse, and rabbit PONs each contain only three cysteine residues, and their positions within PON have been conserved. In purified human PON, residues Cys-41 and Cys-352 form an intramolecular disulfide bond and neither could function as an active-center cysteine. Highly purified, enzymatically active PON contains a single titratable sulfhydryl group. Thus, Cys-283 is the only probable candidate for an active-center cysteine. Through site-directed mutagenesis of the human cDNA, Cys-283 was replaced with either serine (C283S) or alanine (C283A). The expressed C283 (wild-type) enzyme was inactivated by para-hydroxymercuribenzoate, but the C283S and C283A mutant enzymes were not inactivated. C283A and C283S mutant enzymes retained both paraoxonase and arylesterase activities, and the Km values for paraoxon and phenyl acetate were similar to those of the wild type. Clearly, residue Cys-283 is free in active PON, but a free sulfhydryl group is not required for either paraoxonase or arylesterase activities. Consequently, it is necessary to examine other models for the active-site structure and catalytic mechanism of PON.
NH2- and COOH-Terminal Truncations of Murine Granulocyte Chemotactic Protein-2 Augment the In Vitro and In Vivo Neutrophil Chemotactic Potency (1999)

Chemokines are important mediators of leukocyte migration during the inflammatory response. Post-translational modifications affect the biological potency of chemokines. In addition to previously identified NH2-terminally truncated forms, COOH-terminally truncated forms of the CXC chemokine murine granulocyte chemotactic protein-2 (GCP-2) were purified from conditioned medium of stimulated fibroblasts. The truncations generated 28 natural murine GCP-2 isoforms containing 69-92 residues, including most intermediate forms. Both NH2- and COOH-terminal truncations of GCP-2 resulted in enhanced chemotactic potency for human and murine neutrophils in vitro. The truncated isoform GCP-2(9-78) was 30-fold more potent than intact GCP-2(1-92)/LPS-induced CXC chemokine (LIX) at inducing an intracellular calcium increase in human neutrophils. After intradermal injection in mice, GCP-2(9-78) was also more effective than GCP-2(1-92)/LIX at inducing neutrophil infiltration. Similar to human IL-8 and GCP-2, murine GCP-2(9-78) and macrophage inflammatory protein-2 (MIP-2) induced calcium increases in both CXCR1 and CXCR2 transfectants. Murine GCP-2(9-78) could desensitize the calcium response induced by MIP-2 in human neutrophils and vice versa. Furthermore, MIP-2 and truncated GCP-2(9-78), but not intact GCP-2(1-92)/LIX, partially desensitized the calcium response to human IL-8 in human neutrophils. Taken together, these findings point to an important role of post-translationally modified GCP-2 to replace IL-8 in the mouse.
Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolism (2010)

Mutations in the gene encoding the Krebs cycle enzyme fumarate hydratase (FH) predispose to hereditary leiomyomatosis and renal cell cancer in affected individuals. FH-associated neoplasia is characterized by defective mitochondrial function and by upregulation of transcriptional pathways mediated by hypoxia-inducible factor (HIF), although whether and by what means these processes are linked has been disputed. We analysed the HIF pathway in Fh1-/- mouse embryonic fibroblasts (MEFs), in FH-defective neoplastic tissues and in Fh1-/- MEFs re-expressing either wild-type or an extra-mitochondrial restricted form of FH. These experiments demonstrated that upregulation of HIF-1alpha occurs as a direct consequence of FH inactivation. Fh1-/- cells accumulated intracellular fumarate and manifested severe impairment of HIF prolyl but not asparaginyl hydroxylation which was corrected by provision of exogenous 2-oxoglutarate (2-OG). Re-expression of the extra-mitochondrial form of FH in Fh1-/- cells was sufficient to reduce intracellular fumarate and to correct dysregulation of the HIF pathway completely, even in cells that remained profoundly defective in mitochondrial energy metabolism. The findings indicate that upregulation of HIF-1alpha arises from competitive inhibition of the 2-OG-dependent HIF hydroxylases by fumarate and not from disruption of mitochondrial energy metabolism.
Identification of a Novel Gene Family Encoding Human Liver-specific Organic Anion Transporter LST-1 (1999)

We have isolated a novel liver-specific organic anion transporter, LST-1, that is expressed exclusively in the human, rat, and mouse liver. LST-1 is a new gene family located between the organic anion transporter family and prostaglandin transporter. LST-1 transports taurocholate (Km = 13.6 microM) in a sodium-independent manner. LST-1 also shows broad substrate specificity. It transports conjugated steroids (dehydroepiandrosterone sulfate, estradiol-17beta-glucuronide, and estrone-3-sulfate), eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, leukotriene E4), and thyroid hormones (thyroxine, Km = 3.0 microM and triiodothyronine, Km = 2.7 microM), reflecting hepatic multispecificity. LST-1 is probably the most important transporter in human liver for clearance of bile acids and organic anions because hepatic levels of another organic anion transporter, OATP, is very low. This is also the first report of the human molecule that transports thyroid hormones.
Beta‐blocker treatment in heart failure (2001)

Heart failure treatment has markedly changed during the last few decades, with demonstration of benefit of afterload reduction by vasodilator therapy and introduction of the concept of the deleterious consequences of the neuro-hormonal compensatory stimulation. Blockade of beta-adrenergic receptors, initially contra-indicated in heart failure, provide a marked reduction of mortality and morbidity in combination with diuretics and angiotensin-converting enzyme inhibitors, as demonstrated in many clinical trials. We performed a review of all clinical trials that compare beta-blockers vs. placebo in chronic heart failure. Beta-blockers with different pharmacological profiles have been tested, mainly metoprolol, bisoprolol, bucindolol and carvedilol. With progressive dose increment, tolerance of such treatment was generally good, left ventricular function improved, hospitalisations for heart failure were less frequent and mortality was reduced. The meta-analysis of the 16 randomised trials, with at least one death in each treatment group, provides a 24% relative risk reduction for such hospitalisations (95% CI=19%-29%) and 22% reduction for mortality (95% CI=16%-28%). Heterogeneity of beta-blocker effect for mortality was found and related to the non-significant benefit obtained in the BEST trial with bucindolol. When such a trial is excluded, the effect model analysis shows that relative risk reduction (beta-blocker induced benefit) is constant whatever the severity of the disease. The mechanism of beta-blocker induced benefit remains unclear, but is at least partly related to left ventricular function improvement and prevention of severe ventricular arrhythmias. In conclusion, beta-blocker treatment has become an established therapy for heart failure, in combination with diuretics and ACE inhibitors. Complementary informations will be needed to clarify the mechanism of benefit and to define the best therapeutic strategy according to the individual characteristics of patients with heart failure.
The Human Genome (2001)

Today's publication of the draft human genome sequence compiled by J. Craig Venter and colleagues represents just the beginning, not the end, of the effort to decipher the human genome. Both the sequence published in this issue and the one in this week's issue of Nature , compiled by lead author Eric Lander of the public genome consortium, have yet to be finished, with all the i's dotted and the t's crossed. But even in this unpolished state, these two books provide the most comprehensive look at the human genome ever possible; they offer a tantalizing glimpse at the wealth of information contained in the sequence.
Density Functional Theory Study of Sn Adsorption on the CeO2Surface (2011)

The adsorption behaviors and electronic properties of Sn on the CeO2(111) surface were systematically investigated using the density functional theory (DFT) method. Our results suggested that Sn on the hollow site is more stable than that on the top oxygen site at the coverage of 0.25 ML, while Sn on the top oxygen site is the most stable configuration when the coverage of Sn is equal to or higher than 0.5 ML. Charge density difference (CDD) analysis indicates that electrons transfer from the Sn adatom to the substrate, leading to the reduction of Ce4+ to Ce3+ ion, which is in agreement with the experimental spectroscopy. The reduction degree of the substrate increases with the Sn coverage, which is well supported by the CDD and spin-resolved density of states (DOS) of the most stable xSn/CeO2(111) configurations. The adsorption of Sn can partially activate the surface oxygen of ceria. The tentative study of a probe molecule CO adsorption on the Sn/CeO2(111) surface indicates that CO adsorption is enhanced due to the strong tin–ceria interactions.
Role of sugar chains in the in vitro biological activity of human erythropoietin produced in recombinant Chinese hamster ovary cells. (1990)

Human erythropoietin contains three Asn-type and one mucin-type sugar chains. That the branching structure of the outer portion of Asn-type sugar chains is correlated to its biological activity in vivo has been reported recently (Takeuchi, M., Inoue, N., Strickland, T. W., Kubota, M., Wada, M., Shimizu, R., Hoshi, S., Kozutsumi, H., Takasaki, S., and Kobata, A. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 7819-7822). In this study, the effect of trimming of sugar chains on the biological activity in vitro of this hormone was examined by using several glycosidases. Human erythropoietin produced by recombinant Chinese hamster ovary cells showed three times higher activity after desialylation. The activity was not changed significantly by further removal of the mucin-type sugar chain from the hormone, indicating no contribution of this type of sugar chain to the activity of erythropoietin in vitro. Sequential removal of galactose and N-acetylglucosamine from the outer chain moieties of the desialylated Asn-type sugar chains raised the activity of the hormone up to four and five times the intact erythropoietin, respectively. The activation effect was diminished slightly by further removing alpha-mannosyl residues and to a great extent by removing beta-mannosyl residues from the core portions of the Asn-type sugar chains. N-Glycanase digestion of intact erythropoietin resulted in almost complete loss of the activity in vitro. These results indicate that the core portion of the Asn-type sugar chains is necessary for erythropoietin to express its full biological activity in vitro and suggest that removal of the core portion of the sugar chains destroys the active conformation of erythropoietin.
Development of computerized human static strength simulation model for job design (1997)

This article describes the development of models to predict population static strengths and low back forces resulting from common manual exertions in industry. The resulting biomechanical models are shown to be valid for their intended purposes, but limitations still exist. In particular, they are meant to aid in evaluating very slow or static exertions, such as when carefully lifting, pushing, or pulling on heavy objects, but do not allow dynamic exertions to be simulated. It is shown that use of these models in the early design of workplaces and equipment is dependent on the use of computerized homonoids and behavioral-based inverse kinematic algorithms in conjunction with CAD systems. © 1997 John Wiley & Sons, Inc.
2002 OTTO L. WALTER LECTURE: MULTIDISCIPLINARY PRACTICE AND THE EUROPEAN COURT OF JUSTICE (2002)

Lecture: Multidisciplinary Practice and the European Court of Justice.My name is Rick Matasar.I am the Dean of New York Law School, and I'm really pleased to welcome you here on behalf of all my colleagues at the law school.My job is very simple today.It is to set up our conversation with a quick introduction of the panel and its topic, and then it is my great pleasure to turn things over to Terry Cone, who directs the International Law Center here at New York Law School.This series honors Dr. Otto Walter, a 1954 graduate of New York Law School, and I must say that when you look through Otto's incredible record of achievement, it suggests exactly why it is that we are so delighted to have this lecture series in his honor.He was a lawyer in Germany and left that country at a time of great turmoil in its history and came here, and much as many people have discovered when they come to the United States with a foreign law degree, you cannot immediately practice law, and Dr Walter came to this country and set up his own business and eventually received his law degree from New York Law School.He then had a distinguished career as a practitioner, a member of our faculty, and in his honor, this series has been created to talk about things international and, in a very particular way, to talk about things that involve international business transactions and their major impact on the world of commerce between all of us.Our panel today are many distinguished individuals from different walks of life.We have Anthony Huydecoper, who is here from the Netherlands as our Advocate-General with the Supreme Court in the Netherlands.Bob Mac-Crate, who, as we know, is the senior counsel at Sullivan and Cromwell or, as we like to say, the senior counsel to all of us and all of our curious walks of life.And Deborah Schenk, who is here from NYU Law School to lend her expertise as a professor of tax law and one who has been doing a lot of thinking on these questions of multidisciplinary practice.It goes
Adiponectin Reduces Atherosclerosis in Apolipoprotein E-Deficient Mice (2002)

These findings documented for the first time that elevated plasma adiponectin suppresses the development of atherosclerosis in vivo.
An overview of Controller Area Network (1999)

The controller area network is a well-established networking system specifically designed with real-time requirements in mind. Developed in the 1980s by Robert Bosch, its ease of use and low cost has led to its wide adoption throughout the automotive and automation industries. However, for the beginner using CAN may seem somewhat bewildering. This article goes some way into explaining how CAN is used both at the hardware and the software levels.
Polypeptide Synthesis Using the S-Alkyl Thioester of a Partially Protected Peptide Segment. Synthesis of the DNA-Binding Domain of c-Myb Protein (142–193)–NH2 (1991)

Abstract A method for polypeptide synthesis using S-alkyl thioester of a partially protected peptide segment has been developed. The DNA-binding domain of c-Myb protein (142–193) was synthesized by this method to estimate its usefulness. The partially protected peptide segments, Boc–[Lys(Boc)143,144,160]–c-Myb protein(142–163)–SCH2CH2CONH2 and [Lys(Boc)171,182,192]–c-Myb protein(164–193)–NH2, were highly purified from peptides obtained by a solid-phase method. The thioester in the carboxyl component of the peptide segment was converted to the corresponding p-nitrophenyl ester in the presence of silver ions and p-nitrophenol and then the two segments were condensed. The coupling reaction proceeded almost completely yielding a highly-purified product after removal of Boc groups.
Inactivation of the Tuberous Sclerosis Complex-1 and -2 Gene Products Occurs by Phosphoinositide 3-Kinase/Akt-dependent and -independent Phosphorylation of Tuberin (2003)

The tuberous sclerosis complex (TSC) is a genetic disorder that is caused through mutations in either one of the two tumor suppressor genes, TSC1 and TSC2, that encode hamartin and tuberin, respectively. Interaction of hamartin with tuberin forms a heterodimer that inhibits signaling by the mammalian target of rapamycin to its downstream targets: eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). During mitogenic sufficiency, the phosphoinositide 3-kinase (PI3K)/Akt pathway phosphorylates tuberin on Ser-939 and Thr-1462 that inhibits the tumor suppressor function of the TSC complex. Here we show that tuberin-hamartin heterodimers block protein kinase C (PKC)/MAPK- and phosphatidic acid-mediated signaling toward mammalian target of rapamycin-dependent targets. We also show that two TSC2 mutants derived from TSC patients are defective in repressing phorbol 12-myristate 13-acetate-induced 4E-BP1 phosphorylation. PKC/MAPK signaling leads to phosphorylation of tuberin at sites that overlap with and are distinct from Akt phosphorylation sites. Phosphorylation of tuberin by phorbol 12-myristate 13-acetate was reduced by treatment of cells with either bisindolylmaleimide I or UO126, inhibitors of PKC and MAPK/MEK (MAPK/ERK kinase), respectively, but not by wortmannin (an inhibitor of PI3K). This work reveals that both PI3K-independent and -dependent mechanisms modulate tuberin phosphorylation in vivo.
The Stem Cell Continuum (2005)

Hematopoietic stem cells have been felt to exist in a hierarchical structure with a relatively fixed phenotype at each stage of differentiation. Recent studies on the phenotype of the marrow hematopoietic stem cell indicate that it is not a fixed entity, but rather that it fluctuates and shows marked heterogeneity. Past studies have shown that stem cell engraftment characteristics, adhesion protein, and gene expression varies with the phase of the cell cycle. More recently, we demonstrated that progenitor numbers and differentiation potential also vary reversibly during one cytokine-induced cell cycle transit. We have also shown high levels of conversion of marrow cells to skeletal muscle and lung cells, indicating a different level of plasticity. Recently, we demonstrated that homing to lung and conversion to lung cells in a mouse transplant model also fluctuates reversibly with cell cycle transit. This could be considered plasticity squared. These data indicate that marrow stem cells are regulated on a continuum related to the cell cycle both as to hematopoietic and to nonhematopoietic differentiation.
Low-speed rotational angioplasty in chronic peripheral artery occlusions: experience in 83 patients. Work in progress. (1989)

Between December 1986 and October 1988, 83 patients with chronic peripheral artery occlusions were treated with a new technique. In 56 patients, the superficial femoral artery was completely occluded; in 21 patients, the popliteal artery; and in six patients, the iliac artery. The length of occlusion ranged from 5 to 35 cm (mean, 12.5 cm). The duration, estimated by history, was 5-48 months (mean, 16.5 months). In seven patients, durations of 6-36 months were documented angiographically. A flexible, blunt, motor-driven rotating catheter was introduced through an 8-F sheath, and rotational angioplasty was performed at low speed (up to 200 rpm). In 49 of 60 (82%) patients in whom this new technique was used as the primary intervention, the occlusions were successfully reopened. In 23 patients in whom conventional methods had failed more than 4 weeks earlier, the success rate for rotational angioplasty was 67% (12 of 18 patients); when the time interval was less than 4 weeks, only one of five patients was treated successfully. In none of the 83 patients did a perforation occur. This new technique can reopen chronic artery occlusions with a high degree of success and without the danger of vessel-wall perforation, even after failure of conventional techniques.
Temperature Effects on Structural Properties of Pluronic P104 and F108 PEO-PPO-PEO Block Copolymer Solutions (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTemperature Effects on Structural Properties of Pluronic P104 and F108 PEO-PPO-PEO Block Copolymer SolutionsPaschalis Alexandridis, Thierry Nivaggioli, and T. Alan HattonCite this: Langmuir 1995, 11, 5, 1468–1476Publication Date (Print):May 1, 1995Publication History Published online1 May 2002Published inissue 1 May 1995https://pubs.acs.org/doi/10.1021/la00005a011https://doi.org/10.1021/la00005a011research-articleACS PublicationsRequest reuse permissionsArticle Views4425Altmetric-Citations294LEARN 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
Multilineage Cells from Adipose Tissue as Gene Delivery Vehicles (2003)

We have characterized a population of mesenchymal progenitor cells from adipose tissue, termed processed lipoaspirate (PLA) cells, which have multilineage potential similar to bone marrow-derived mesenchymal stem cells and are also easily expanded in culture. The primary benefit of using adipose tissue as a source of multilineage progenitor cells is its relative abundance and ease of procurement. We examined the infection of PLA cells with adenoviral, oncoretroviral, and lentiviral vectors. We demonstrate that PLA cells can be transduced with lentiviral vectors at high efficiency. PLA cells maintain transgene expression after differentiation into adipogenic and osteogenic lineages after lentiviral transduction. Therefore, PLA cells and lentiviral vectors may be an efficient combination for use as a therapeutic gene delivery vehicle.
Development of Navigation System for Autonomous Vehicle to Meet the DARPA Urban Grand Challenge (2007)

Spring Light team is the first, and the only, Asian team registered to the 2007 DARPA Urban Grand Challenge. In this paper, we present the navigation system of the Daughter Dragon vehicle of the spring light team. The purpose of the navigation is two fold. First of all, it takes the road map, the mission description file and in-vehicle GPS data as input, and plans in real-time an optimized route connecting the vehicle's actual position to the destination point as output. The optimization criteria considered in this work include the shortest traveling time, the shortest traveling distance, and the minimum number of traversed junctions. Second, the navigation system receives the data from visual perception such as laser-range finder, and generates a trajectory in terms of the vehicle's steering angle profile and velocity profile as output. In this paper, we detail the algorithms implemented inside the proposed navigation system. And, the proposed navigation system has been fully tested with simulations. Real experiments are actually undertaking, and will be presented in the conference.