gebhart/patrepeval huggingface dataset:
Double Anti-angiogenic and Anti-inflammatory Protein Valpha Targeting VEGF-A and TNF-α in Retinopathy and Psoriasis (2011)

Pathological angiogenesis usually involves disrupted vascular integrity, vascular leakage, and infiltration of inflammatory cells, which are governed mainly by VEGF-A and TNF-α. Although many inhibitors targeting either VEGF-A or TNF-α have been developed, there is no single inhibitor molecule that simultaneously targets both molecules. Here, we designed and generated a novel chimeric decoy receptor (Valpha) that can simultaneously bind to VEGF-A and TNF-α and block their actions. In this experimental design, we have shown that Valpha, which is an effective synchronous blocker of VEGF-A and TNF-α, can drastically increase treatment effectiveness through its dual-blocking characteristics. Valpha contains the VEGF-A-binding domain of VEGFR1, the TNF-α-binding domain of TNFR2, and the Fc domain of IgG1. Valpha exhibited strong binding characteristics for its original counterparts, VEGF-A and TNF-α, but not for the extracellular matrix, resulting in a highly favorable pharmacokinetic profile in vivo. Compared with VEGF-Trap or Enbrel, both of which block either VEGF-A or TNF-α, singularly, Valpha is a highly effective molecule for reducing abnormal vascular tufts and the number of F4/80(+) macrophages in a retinopathy model. In addition, Valpha showed superior relief effects in a psoriasis model with regard to epidermal thickness and the area of blood and lymphatic vessels. Thus, the simultaneous blocking of VEGF-A and TNF-α using Valpha is an effective therapeutic strategy and cost-efficient for treatment of retinopathy and psoriasis.
T cell costimulatory pathways: blockade for autoimmunity (2003)

AbstractThe activation of T lymphocytes is thought to require at least two signals, one delivered by the T cell receptor (TCR) complex after antigen recognition, and one provided on engagement of costimulatory receptors. The B7-1/B7-2–CD28/cytotoxic T lymphocyte antigen-4 (CTLA-4) and CD154–CD40 pathways have been shown to be crucial in regulating T cell activation and tolerance. Novel members of the B7–CD28 superfamily have recently been discovered and they seem to be particularly important for regulating the responses of previously activated T cells. Superimposition of inhibitory signals like those delivered by CTLA-4 and programmed death (PD)-1–PD-1-ligand (PD-L1) pathway leads to a complex network of positive and negative costimulatory signals, the integration of which modulates immune responses. Furthermore, expression of several B7 homologues on cells other than professional antigen-presenting cells (APCs), indicate new mechanisms for regulating T cell responses in peripheral tissues. This review focuses on our current understanding of the members of the B7–CD28 superfamily and discusses their therapeutic potential.KeywordsautoimmunityCD28costimulationCTLA-4ICOSPD-1
Alemtuzumab Induction Prior to Cardiac Transplantation with Lower Intensity Maintenance Immunosuppression: One-Year Outcomes (2009)

Induction therapy with alemtuzumab (C-1H) prior to cardiac transplantation (CTX) may allow for lower intensity maintenance immunosuppression. This is a retrospective study of patients who underwent CTX at a single institution from January 2001 until April 2009 and received no induction versus induction with C-1H on a background of tacrolimus and mycophenolate. Those with C-1H received dose-reduced calcineurin inhibitor and no steroids. A total of 220 patients were included, 110 received C-1H and 110 received no induction. Recipient baseline characteristics, donor age and gender were not different between the two groups. Mean tacrolimus levels (ng/mL) for C-1H versus no induction: months 1-3 (8.5 vs. 12.9), month 4-6 (10.2 vs. 13.0), month 7-9 (10.2 vs. 11.9) and month 10-12 (9.9 vs. 11.3) were all significantly lower for the C-1H group, p < 0.001. There were no differences between the C-1H and no induction groups at 12 months for overall survival 85.1% versus 93.6% p = 0.09, but freedom from significant rejection was significantly higher for the C-1H group, 84.5% versus 51.6%, p < 0.0001. In conclusion, induction therapy after CTX with C-1H results in a similar 12 month survival, but a greater freedom from rejection despite lower calcineurin levels and without the use of steroids.
Comparison of the factor VII:C clot analysis and a modified activated factor VII analysis for monitoring factor VII activity in patients treated with recombinant activated factor VII (NovoSeven®) (2000)

Bleeding episodes in haemophilia A and B inhibitor patients are now frequently treated with recombinant activated factor VII (NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark). Until now, the FVII:C coagulation assay has been used to monitor NovoSeven-mediated coagulation. However, a new assay (Staclot VIIa-rTF, Diagnostica Stago, France) has been designed to specifically detect activated factor (F)VII. Replacement of the buffer supplied by the manufacturer with a PIPES buffer containing BSA (modified FVIIa assay), resulted in a linear standard curve, greater sample stability and a reduced coefficient of variation. The FVII:C assay and the modified FVIIa assay were compared in a recovery experiment using the International FVIIa standard No 89/688(IS). Recovery of FVIIa was 93-97% for the modified FVIIa assay and 91-115% for the FVII:C assay. However, because samples in the FVII:C assay were not parallel to the standard curve, confidence limits for recovery were as wide as 67-130% compared with 92-106% for the FVIIa assay. In conclusion, a modified version of the Staclot VIIa-rTF assay, suitable for monitoring treatment with NovoSeven, even at low concentrations, has been developed. It provides an alternative to the FVII:C assay, which is not suitable for monitoring FVIIa at low concentrations.
Diameter-Dependent Growth Direction of Epitaxial Silicon Nanowires (2005)

We found that silicon nanowires grown epitaxially on Si (100) via the vapor-liquid-solid growth mechanism change their growth direction from 111 to 110 at a crossover diameter of approximately 20 nm. A model is proposed for the explanation of this phenomenon. We suggest that the interplay of the liquid-solid interfacial energy with the silicon surface energy expressed in terms of an edge tension is responsible for the change of the growth direction. The value of the edge tension is estimated by the product of the interfacial thickness with the surface energy of silicon. For large diameters, the direction with the lowest interfacial energy is dominant, whereas for small diameters the surface energy of the silicon nanowire determines the preferential growth direction.
Inositol regulates phosphatidylglycerolphosphate synthase expression in Saccharomyces cerevisiae. (1988)

The enzyme phosphatidylglycerolphosphate synthase (PGPS; CDPdiacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase; EC 2.7.8.5) catalyzes the committed step in the synthesis of cardiolipin, a phospholipid found predominantly in the mitochondrial inner membrane. To determine whether PGPS is regulated by cross-pathway control, we analyzed PGPS expression under conditions in which the regulation of general phospholipid synthesis could be examined. The addition of inositol resulted in a three- to fivefold reduction in PGPS expression in wild-type cells in the presence or absence of exogenous choline. The reduction in enzyme activity in response to inositol was seen in minutes, suggesting that inactivation or degradation of the enzyme plays an important role in inositol-mediated repression of PGPS. In cho2 and opi3 mutants, which are blocked in phosphatidylcholine synthesis, inositol-mediated repression of PGPS did not occur unless choline was added to the media. Three previously identified genes that regulate general phospholipid synthesis, INO2, INO4, and OP11, did not affect PGPS expression. Thus, ino2 and ino4 mutants, which are unable to derepress biosynthetic enzymes involved in general phospholipid synthesis, expressed wild-type levels of PGPS activity under derepressing conditions. PGPS expression in the opi1 mutant, which exhibits constitutive synthesis of general phospholipid biosynthetic enzymes, was fully repressed in the presence of inositol and partially repressed even in the absence of inositol. These results demonstrate for the first time that an enzymatic step in cardiolipin synthesis is coordinately controlled with general phospholipid synthesis but that this control is not mediated by the same genetic regulatory circuit.
Mushroom Tyrosinase Inhibition Activity of Some Chromones. (2002)

Currently, aloesin is used in the cosmetic industry as a whitening agent because it inhibits tyrosinase activity. Aloesin is a C-glycosylated chromone compound isolated from aloe, and it is difficult to synthesize because of C-glycosyl moiety in the molecule. The purpose of this study is to search for a new chromone compound which is easy to synthesize and which posesses stronger tyrosinase inhibitory activity than aloesin. Fourteen chromone derivatives were synthesized and screened for their mushroom-tyrosinase inhibitory activity. 5-Methyl-7-methoxy-2-(2'-benzyl-3'-oxobutyl)chromone (15) showed the strongest activity among tested compounds. Its activity was not only stronger than aloesin, but also stronger than arbutin and kojic acid. The kinetic analysis revealed a competitive inhibition of 15 with tyrosinase for the L-tyrosine binding site.
A multivariable neural controller for automatic ship berthing (1997)

This article describes the development and application of a multivariable neural controller for automatic ship berthing. Following a brief review of various methods employed in automatic ship control, an online trained, backpropagation-based neural network controller is presented. The principal intention is to take advantage of the learning ability of neural networks, and to derive an autonomous neural control algorithm which is independent of the mathematical model of the ship. The proposed neural network controller is designed to adjust its parameters online from a direct evaluation of performance accuracy, thereby eliminating the need for off-line training and a "trainer" associated with supervised control. In addition, the nonlinearity of the rudder and the transfer lag of the propeller have been considered in the system design to increase the realism of the simulation. A series of simulation studies, which include wind disturbances and shallow water effects, have been undertaken to demonstrate the adaptive features and the robust performance of the proposed neural control scheme.
Square Root SAM: Simultaneous Localization and Mapping via Square Root Information Smoothing (2006)

Solving the SLAM (simultaneous localization and mapping) problem is one way to enable a robot to explore, map, and navigate in a previously unknown environment. Smoothing approaches have been investigated as a viable alternative to extended Kalman filter (EKF)-based solutions to the problem. In particular, approaches have been looked at that factorize either the associated information matrix or the measurement Jacobian into square root form. Such techniques have several significant advantages over the EKF: they are faster yet exact; they can be used in either batch or incremental mode; are better equipped to deal with non-linear process and measurement models; and yield the entire robot trajectory, at lower cost for a large class of SLAM problems. In addition, in an indirect but dramatic way, column ordering heuristics automatically exploit the locality inherent in the geographic nature of the SLAM problem. This paper presents the theory underlying these methods, along with an interpretation of factorization in terms of the graphical model associated with the SLAM problem. Both simulation results and actual SLAM experiments in large-scale environments are presented that underscore the potential of these methods as an alternative to EKF-based approaches.
An adjuvant-modulated vaccine response in human whole blood (2017)

The restimulation of an immune memory response by in vitro culture of blood cells with a specific antigen has been used as a way to gauge immunity to vaccines for decades. In this commentary we discuss a less appreciated application to support vaccine process development. We report that human whole blood from pre-primed subjects can generate a profound adjuvant-modulated, antigen-specific response to several different vaccine formulations. The response is able to differentiate subtle changes in the quality of an immune memory response to vaccine formulations and can be used to select optimal conditions relating to a particular manufacture process step. While questions relating to closeness to in vivo vaccination remain, the approach is another big step nearer to the more relevant human response. It has special importance for new adjuvant development, complementing other preclinical in vivo and in vitro approaches to considerably de-risk progression of novel vaccines before and throughout early clinical development. Broader implications of the approach are discussed.
Xylitol Pediatric Topical Oral Syrup to Prevent Dental Caries (2009)

Xylitol oral syrup administered topically 2 or 3 times daily at a total daily dose of 8 g was effective in preventing early childhood caries.
Small RNAs and Small Proteins Involved in Resistance to Cell Envelope Stress and Acid Shock in Escherichia coli : Analysis of a Bar-Coded Mutant Collection (2009)

More than 80 small regulatory RNAs (sRNAs) and 60 proteins of 16 to 50 amino acids (small proteins) are encoded in the Escherichia coli genome. The vast majority of the corresponding genes have no known function. We screened 125 DNA bar-coded mutants to identify novel cell envelope stress and acute acid shock phenotypes associated with deletions of genes coding for sRNAs and small proteins. Nine deletion mutants (ssrA, micA, ybaM, ryeF, yqcG, sroH, ybhT, yobF, and glmY) were sensitive to cell envelope stress and two were resistant (rybB and blr). Deletion mutants of genes coding for four small proteins (yqgB, mgrB, yobF, and yceO) were sensitive to acute acid stress. We confirmed each of these phenotypes in one-on-one competition assays against otherwise-wild-type lacZ mutant cells. A more detailed investigation of the SsrA phenotype suggests that ribosome release is critical for resistance to cell envelope stress. The bar-coded deletion collection we generated can be screened for sensitivity or resistance to virtually any stress condition.
Clinical and Biochemical Assessment of Hypogonadism in Men With Type 2 Diabetes (2007)

Testosterone levels are frequently low in men with type 2 diabetes, and the majority of these men have symptoms of hypogonadism. Obesity is associated with low testosterone levels in diabetic men.
Cellstat—A continuous culture system of a bacteriophage for the study of the mutation rate and the selection process at the DNA level (1982)

A bacteriophage is continuously cultured in the flow of the host bacterial cell under the control of a minicomputer. In the culture, the population of the noninfected cell is kept constant by the endogeneous regulation mechanism, so it is called the ’’cellstat’’ culture. Due to the high dilution rate of the host cell, the mutant cell cannot be selected in the cellstat. Therefore, the cellstat is suitable for the study of the mutation rate and the selection process of a bacteriophage under well-defined environmental conditions (including physiological condition of the host cell) without being interfered by host-cell mutations. Applications to coliphage fd, a secretion type phage, are shown as a measurement example. A chimera between fd and a plasmid pBR322 is cultured more than 100 h. The process of population changeovers by deletion mutants indicates that the deletion hot spots exist in this cloning vector and that this apparatus can be used also for testing instability of a recombinant DNA.
Synthesis and tautomeric equilibrium of 6-amino-5-benzyl-3-methylpyrazin-2-one. An acceptor-donor-donor nucleoside base analog (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and tautomeric equilibrium of 6-amino-5-benzyl-3-methylpyrazin-2-one. An acceptor-donor-donor nucleoside base analogJohannes J. Voegel, Ulrike von Krosigk, and Steven A. BennerCite this: J. Org. Chem. 1993, 58, 26, 7542–7547Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://pubs.acs.org/doi/10.1021/jo00078a038https://doi.org/10.1021/jo00078a038research-articleACS PublicationsRequest reuse permissionsArticle Views226Altmetric-Citations33LEARN 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
Fragile X Syndrome (2011)

Recent data from a national survey highlighted a significant difference in obesity rates in young fragile X males (31%) compared to age matched controls (18%). Fragile X syndrome (FXS) is the most common cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (>200) on the promotor region of the fragile X mental retardation 1 gene (FMR1). As a result, the promotor region often becomes methylated which leads to a deficiency or absence of the FMR1 protein (FMRP). Common characteristics of FXS include mild to severe cognitive impairments in males but less severe cognitive impairment in females. Physical features of FXS include an elongated face, prominent ears, and post-pubertal macroorchidism. Severe obesity in full mutation males is often associated with the Prader-Willi phenotype (PWP) which includes hyperphagia, lack of satiation after meals, and hypogonadism or delayed puberty; however, there is no deletion at 15q11-q13 nor uniparental maternal disomy. Herein, we discuss the molecular mechanisms leading to FXS and the Prader-Willi phenotype with an emphasis on mouse FMR1 knockout studies that have shown the reversal of weight increase through mGluR antagonists. Finally, we review the current medications used in treatment of FXS including the atypical antipsychotics that can lead to weight gain and the research regarding the use of targeted treatments in FXS that will hopefully have a significantly beneficial effect on cognition and behavior without weight gain.
Clarifications on the Routing of Diameter Requests Based on the Username and the Realm (2009)

This specification defines the behavior required of Diameter agents to
route requests when the User-Name Attribute Value Pair contains a
Network Access Identifier formatted with multiple realms. These multi-
realm, or Decorated, Network Access Identifiers are used in order to
force the routing of request messages through a predefined list of
mediating realms. [STANDARDS-TRACK]
Overview of a compiler for synthesizing MATLAB programs onto FPGAs (2004)

This paper describes a behavioral synthesis tool called AccelFPGA which reads in high-level descriptions of digital signal processing (DSP) applications written in MATLAB, and automatically generates synthesizable register transfer level (RTL) models and simulation testbenches in VHDL or Verilog. The RTL models can be synthesized using commercial logic synthesis tools and place and route tools onto field-programmable gate arrays (FPGAs). This paper describes how powerful directives are used to provide high-level architectural tradeoffs for the DSP designer. Experimental results are reported on a set of eight MATLAB benchmarks that are mapped onto the Xilinx Virtex II and Altera Stratix FPGAs.
NMR-Based Model of an Ecteinascidin 743−DNA Adduct (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNMR-Based Model of an Ecteinascidin 743−DNA AdductBob M. Moore, Frederick C. Seaman, and Laurence H. HurleyView Author Information Drug Dynamics Institute, College of Pharmacy The University of Texas at Austin, Austin, Texas 78712-1074 Cite this: J. Am. Chem. Soc. 1997, 119, 23, 5475–5476Publication Date (Web):June 11, 1997Publication History Received11 February 1997Published online11 June 1997Published inissue 1 June 1997https://pubs.acs.org/doi/10.1021/ja9704500https://doi.org/10.1021/ja9704500rapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views612Altmetric-Citations65LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Alcohols,Biopolymers,Genetics,Noncovalent interactions,Nucleic acid structure Get e-Alerts
Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. (1999)

Internal tandem duplication of the FLT3 gene and point mutations of the N-RAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). However, their prognostic importance is unclear. In this study, their prognostic significance was analyzed in 201 newly diagnosed patients with de novo AML except acute promyelocytic leukemia. Three patients had mutations in both genes, 43 had only the FLT3 gene mutation, 25 had only the N-RAS gene mutation, and 130 had neither. These mutations seemed to occur independently. Both mutations were related to high peripheral white blood cell counts, and the FLT3 gene mutation was infrequently observed in the French-American-British (FAB)-M2 type. AML cases with wild FLT3/mutant N-RAS had a lower complete remission (CR) rate than those with wild FLT3/wild N-RAS, whereas the presence of mutant FLT3 did not affect the CR rate. Univariate analysis showed that unfavorable prognostic factors for overall survival were age 60 years or older (P =.0002), cytogenetic data (P =.002), FAB types other than M2 (P =.002), leukocytosis over 100 +/- 10(9)/L (P =.003), and the FLT3 gene mutation (P =.004). However, the N-RAS gene mutation was only a marginal prognostic factor (P =.06). For the subjects under 60 years old, multivariate analysis showed that the FLT3 gene mutation was the strongest prognostic factor (P =.008) for overall survival. The FLT3 gene mutation, whose presence is detectable only by genomic polymerase chain reaction amplification and gel electrophoresis, might serve as an important molecular marker to predict the prognosis of patients with AML.