gebhart/patrepeval huggingface dataset:
Use of Sphingosine-1-Phosphate 1 Receptor Agonist, KRP-203, in Combination with a Subtherapeutic Dose of Cyclosporine A for Rat Renal Transplantation (2006)

Background. We demonstrate the long-term effectiveness of KRP-203 treatment in combination with a subtherapeutic dose of cyclosporine A (CsA) on rat renal allografts. Methods. We tested the effect of KRP-203 in combination with CsA using a rat skin allograft model. The Pharmacokinetic interaction between CsA and KRP-203 was evaluated. The selectivity of KRP-203 for sphingosine-1-phosphate (S1P)1 and S1P3 receptors were investigated in vitro. Heart rate alteration following bolus injection of phosphorylated KRP-203 (KRP-203-P) or FTY720 (FTY720-P) was also monitored in rats. Finally, the long-term effectiveness of KRP-203 in conjunction with a low dose of CsA was investigated in a rat renal transplantation model. Results. Administration of KRP-203 with CsA prolonged skin allograft survival. KRP-203 and CsA had no effect on the pharmacokinetics of the other. While FTY720-P activated both S1P1 and S1P3 receptors, KRP-203-P selectively activated S1P1, but not the S1P3 receptor (EC50: >1000 nM). Compared to FTY720-P, a tenfold higher dose of KRP-203-P was necessary to induce transient bradycardia. With a low dose of CsA (1 mg/kg/day), KRP-203 (0.3 mg/kg/day) significantly prolonged renal allograft survival (P<0.05, survival time: 9.8 days (CsA) vs. >27.4 days (CsA+KRP)). Although a higher dose of CsA (3 mg/kg/day) alone kept recipients alive, this caused severe renal graft dysfunction. Use of KRP-203 (3 mg/kg/day) in conjunction with CsA markedly improved graft function (P<0.05, creatinine clearance: 0.41±0.25 ml/min [CsA] vs. 1.15±0.16 ml/min [CsA+KRP]). Conclusions. The selectivity of KRP-203 for S1P1 reduces the risk of bradycardia, and the combination therapy of KRP-203 with CsA represents a safe and effective strategy for use in renal transplantation.
Evaluation of Dislocation Generation at Si3 N 4 Film Edges on Silicon Substrates by Selective Oxidation (1981)

The density of dislocations generated at film edges on silicon substrate by selective oxidation is measured and the relation between the selective oxidation conditions and dislocation generation at the film edges is investigated. Dislocations are observed using Secco etching. The results show that the density of dislocations does not continuously increase with oxidation temperature, but decreases markedly at temperatures above 1000°C. A further experiment with recessed oxide structure reveals that the generation of dislocations depends strongly on the cross‐sectional structure of the sample These results are interpreted in terms of viscous flow of film. Another experiment suggests that high pressure oxidation is not effective for suppressing dislocation generation, although it is useful for reducing oxidation time. Finally, collector‐emitter shorts of transistors in bipolar integrated circuits are examined quantitatively using a simple statistical method in relation to the dislocations generated at film edges.
In vitro degradation of some arginine-vasopressin analogs by homogenates of rat kidney, liver and serum. (1992)

Enzymatic degradations of arginine-vasopressin (AVP) and its [7-sarcosine]-substituted analogs were performed using homogenates of rat kidney, liver and serum. Under the experimental conditions used in this work, [Sar7]AVP and the parent hormone were inactivated much faster by the kidney cortex and liver homogenates than the remaining analogs, which were additionally modified at position 1 and did not contain the N-terminal amino group. Analytical data of the degradation products showed that, in the case of AVP and [Sar7]AVP, there were two major sites of cleavage: Tyr-Phe and Arg-Gly. The analogs which lack free N-terminal amino groups were deactivated very slowly. In these cases the main degradation product resulted from the cleavage of the Arg-Gly bond. The most surprising result observed during the incubation of AVP and its analogs with rat serum was the relatively high enzymatic stability of the parent hormone compared with the modified analogs. In contrast, the fastest degradation rate was found for [Cpp1,Sar7]AVP, which contains the bulky cyclopentamethylene moiety in position 1. The cleavage of the Arg-Gly peptide bond was exclusively responsible for the inactivation of all peptides with rat serum. The results showed that the degradation of vasopressin analogs in various blood and tissue samples differed both in speed and pattern of inactivation.
The immunobiology and clinical potential of immunostimulatory CpG oligodeoxynucleotides (2000)

Over 100 years ago, Coley first explored the use of bacterial products as immunostimulatory therapy for nonbacterial disease. It is now clear that bacterial DNA, and synthetic oligodeoxynucleotides containing specific motifs centered on a CpG dinucleotide (CpG ODN), are potent immunostimulatory agents. The molecular mechanisms responsible for the immunostimulatory effects of CpG ODN have yet to be elucidated fully, although it is clear that CpG ODN act rapidly on a variety of cell types. This includes activation of B cells, natural killer cells, and antigen-presenting cells including monocytes, macrophages, and dendritic cells. These effects have led to evaluation of CpG ODN as immune adjuvants in immunization where they have been shown in animal models to enhance the development of a TH1-type immune response. Preliminary results from clinical trials using CpG ODN as an immune adjuvant are promising. Preclinical studies suggest CpG ODN can also enhance innate immunity against a variety of infections, synergize with monoclonal antibody to enhance antibody-dependent cellular cytotoxicity, and alter the Th1/Th2 balance as a possible treatment for allergic diseases and asthma. Clinical evaluation has recently begun to determine whether promising preclinical results with CpG ODN can be translated into effective and tolerable clinical treatment approaches.
Solution and Optimization of Systems of Pseudo-Boolean Constraints (2007)

Optimized solvers for the Boolean satisfiability (SAT) problem have many applications in areas such as hardware and software verification, FPGA routing, planning, and so forth. Further uses are complicated by the need to express "counting constraints" in conjunctive normal form (CNF). Expressing such constraints by pure CNF leads to more complex SAT instances. Alternatively, those constraints can be handled by integer linear programming (ILP), but generic ILP solvers may ignore the Boolean nature of 0-1 variables. Therefore, specialized 0-1 ILP solvers extend SAT solvers to handle these so-called "pseudo-Boolean" (PB) constraints. This work provides an update on the on-going competition between generic ILP techniques and specialized 0-1 ILP techniques. To make a fair comparison, we generalize recent ideas for fast SAT-solving to more general 0-1 ILP problems that may include counting constraints and optimization. This generalization is embodied in our PB constraint solver and optimizer PBS, which is compared with state-of-the-art CNF and generic ILP solvers. Another aspect of our comparison is the evaluation on 0-1 ILP benchmarks that originate in electronic design automation (EDA) but that cannot be directly solved by an SAT solver. Specifically, we solve instances of the max-SAT and max-ONEs optimization problems, which seek to maximize the number of satisfied clauses and the "true" values over all satisfying assignments, respectively. Those problems have straightforward applications to SAT-based routing and are additionally important due to reductions from max-cut, max-clique, and min vertex cover. Our experimental results show that specialized 0-1 techniques implemented in PBS tend to outperform generic ILP techniques on Boolean optimization problems, as well as on general EDA SAT problems.
An integrated circuit/architecture approach to reducing leakage in deep-submicron high-performance I-caches (2002)

Deep-submicron CMOS designs maintain high transistor switching speeds by scaling down the supply voltage and proportionately, reducing the transistor threshold voltage. Lowering the threshold voltage increases leakage energy dissipation due to subthreshold leakage current even when the transistor is for switching. Estimates suggest a five-fold increase in leakage energy in every future generation. In modern microarchirectures, much of the leakage energy is dissipated in large on-chip cache memory structures with high transistor densities. While cache utilization varies both within and across applications, modern cache designs are fixed in size resulting in transistor leakage inefficiencies. This paper explores an integrated architectural and circuit level approach to reducing leakage energy in instruction caches (i-caches). At the architectural level, we propose the Dynamically Resizable i-cache (DRI i-cache), a novel i-cache design that dynamically resizes and adapts to an application's required size. At the circuit-level, we use gated-V/sub dd/, a mechanism that effectively turns of the supply voltage to, and eliminates leakage in, the SRAM cells in a DRI i-cache's unused sections. Architectural and circuit-level simulation results indicate that a DRI i-cache successfully and robust exploits the cache size variability both within and across applications. Compared to a conventional i-cache using an aggressively-scaled threshold voltage a 64K DRI i-cache reduces on average both the leakage energy-delay product and cache size 62%, with less than 4% impact on execution time.
Olfactory Deficits in Patients With Mild Cognitive Impairment Predict Alzheimer’s Disease at Follow-Up (2000)

In patients with mild cognitive impairment, olfactory identification deficits, particularly with lack of awareness of olfactory deficits, may have clinical utility as an early diagnostic marker for Alzheimer's disease.
A putative receptor for Venezuelan equine encephalitis virus from mosquito cells (1996)

We have identified a cellular protein from a continuous mosquito cell line (C6/36) that appears to play a significant role in the attachment of Venezuelan equine encephalitis (VEE) virus to these cells. VEE virus bound to a 32-kDa polypeptide present in the C6/36 plasma membrane fraction, and binding to this polypeptide was dose dependent and saturable and competed with homologous and heterologous alphaviruses. These observations suggest that this polypeptide binds virus via a receptor-ligand interaction. The 32-kDa polypeptide was expressed on the surfaces of C6/36 cells, and monoclonal antibodies directed against either this cell polypeptide or the VEE virus E2 glycoprotein, which is thought to be the viral attachment protein, interfered with virus attachment. Collectively, these data provide evidence suggesting that the 32-kDa polypeptide serves as a receptor for VEE virus infection of cells. We have characterized this cell polypeptide as a laminin-binding protein on the basis of its ability to interact directly with laminin as well as its immunologic cross-reactivity with the high-affinity human laminin receptor.
Brian: a simulator for spiking neural networks in Python (2008)

"Brian" is a new simulator for spiking neural networks, written in Python (http://brian. di.ens.fr). It is an intuitive and highly flexible tool for rapidly developing new models, especially networks of single-compartment neurons. In addition to using standard types of neuron models, users can define models by writing arbitrary differential equations in ordinary mathematical notation. Python scientific libraries can also be used for defining models and analysing data. Vectorisation techniques allow efficient simulations despite the overheads of an interpreted language. Brian will be especially valuable for working on non-standard neuron models not easily covered by existing software, and as an alternative to using Matlab or C for simulations. With its easy and intuitive syntax, Brian is also very well suited for teaching computational neuroscience.
Cytochrome c Oxidase Subassemblies in Fibroblast Cultures from Patients Carrying Mutations in COX10, SCO1, or SURF1 (2004)

Cytochrome c oxidase contains two redox-active copper centers (Cu(A) and Cu(B)) and two redox-active heme A moieties. Assembly of the enzyme relies on several assembly factors in addition to the constituent subunits and prosthetic groups. We studied fibroblast cultures from patients carrying mutations in the assembly factors COX10, SCO1, or SURF1. COX10 is involved in heme A biosynthesis. SCO1 is required for formation of the Cu(A) center. The function of SURF1 is unknown. Immunoblot analysis of native gels demonstrated severely decreased levels of holoenzyme in the patient cultures compared with controls. In addition, the blots revealed the presence of five subassemblies: three subassemblies involving the core subunit MTCO1 but apparently no other subunits; a subassembly containing subunits MTCO1, COX4, and COX5A; and a subassembly containing at least subunits MTCO1, MTCO2, MTCO3, COX4, and COX5A. As some of the subassemblies correspond to known assembly intermediates of human cytochrome c oxidase, we think that these subassemblies are probably assembly intermediates that accumulate in patient cells. The MTCO1.COX4.COX5A subassembly was not detected in COX10-deficient cells, which suggests that heme A incorporation into MTCO1 occurs prior to association of MTCO1 with COX4 and COX5A. SCO1-deficient cells contained accumulated levels of the MTCO1.COX4.COX5A subassembly, suggesting that MTCO2 associates with the MTCO1.COX4.COX5A subassembly after the Cu(A) center of MTCO2 is formed. Assembly in SURF1-deficient cells appears to stall at the same stage as in SCO1-deficient cells, pointing to a role for SURF1 in promoting the association of MTCO2 with the MTCO1.COX4.COX5A subassembly.
Brain N -acetylaspartate levels correlate with motor function in metachromatic leukodystrophy (2010)

We suggest that NAA levels could serve as a sensitive biomarker in children with MLD. Proton MRS may provide a valuable tool for measuring the effects of treatment interventions in this disorder.
Optimum design using radial basis function networks by adaptive range genetic algorithms (determination of radius in radial basis function networks) (2002)

We use the radial basis function (RBF) network to approximate the fitness function of genetic algorithms and try to obtain approximate optimum results. A RBF is a kind of neural network that is composed of a number of radial basis functions in a Gaussian distribution. When the positions of the basis functions and their radii are given, the learning system of the RBF is summarized in the calculation of the inverse matrix. Thus, the learning system is quite simple and very rapid. There are two important issues in a RBF: one is to place the basis functions and to give data, and the other is to give an appropriate radius to each radial basis function. For the first issue, we have proposed a data distribution and basis function distribution method, together with adaptive-range genetic algorithms (ARange GAs). In this study, we focus our attention on the second problem. For that purpose, we give an oval distribution for the basis functions and assume that every basis function has the same oval radius. In this way, we can reduce the number of radius functions as we reduce the number of design variables. We show the effectiveness of the proposed method through a benchmark problem.
Clinical Relevance of Age-Related Immune Dysfunction (2000)

Immunosenescence is the state of dysregulated immune function that contributes to the increased susceptibility to infection of the elderly. Extensive studies of inbred laboratory animals and very healthy elderly humans have identified changes in immunity; these studies have identified limited phenotypic and functional changes in the T cell component of adaptive immunity. However, no compelling scientific evidence has shown that these changes have direct relevance to the common infections seen in the aged population. This perspective will attempt to shed light on this dilemma. First, it will review clinically relevant infections in the elderly, focusing on influenza and influenza virus vaccination and how chronic illness contributes to increased risk and severity of infection and/or failed vaccine response. Second, key changes in immunity will be reviewed, keeping a perspective of the impact of confounding variables in addition to age but focusing on age-related changes in the interaction of the innate and acquired components of immunity. If the goal is to prevent serious infections in the elderly, it appears that the field of geriatric immunology and/or infectious diseases is faced with the tremendous challenge of studying a very diverse population, including mildly immunocompromised/chronically ill individuals and very healthy elderly.
Automated Classification of Usual Interstitial Pneumonia Using Regional Volumetric Texture Analysis in High-Resolution Computed Tomography (2014)

Our results are encouraging and suggest that an automated system may be useful in routine clinical practice as a diagnostic aid for identifying patients with complex lung disease such as classic UIP, obviating the need for invasive surgical lung biopsy and its associated risks.
A New Multicomponent Reaction Catalyzed by a [Lewis Acid]+[Co(CO)4]- Catalyst:  Stereospecific Synthesis of 1,3-Oxazinane-2,4-diones from Epoxides, Isocyanates, and CO (2007)

The use of mechanistic information to develop a new, catalytic multicomponent reaction is described. The complex [(salph)Al(THF)2]+[Co(CO)4]- (1, salph = N,N'-o-phenylenebis(3,5-di-tert-butylsalicylideneimine), THF = tetrahydrofuran), which is known to carbonylate epoxides, aziridines, and beta-lactones, was used to catalyze the synthesis of 1,3-oxazinane-2,4-diones from epoxides, isocyanates, and CO. Under optimized conditions, the reaction was both selective and high-yielding. 1,3-Oxazinane-2,4-diones were synthesized from a variety of epoxides and isocyanates, including some epoxides that do not undergo simple ring-expansion carbonylation. The best results were obtained using highly electrophilic isocyanates. The mechanism of the multicomponent reaction was investigated using labeling and stereochemistry, and the data obtained were consistent with the 1-catalyzed formation of beta-lactone and 1,3-oxazinane-2,4-dione from a common intermediate.
Hyaluronidase in ram semen. Quantitative determination, and isolation of multiple forms (1988)

A study was made of hyaluronidase in ram semen. The end-group assay conditions used to determine activity quantitatively were chosen to ensure reliability as well as sensitivity [Gacesa, Savitsky, Dodgson & Olavesen (1981) Anal. Biochem. 118, 76-84]; they led to 1 W.H.O. Standard International Hyaluronidase Unit displaying 0.1263 EC munit (1 EC unit of activity releases 1 mumol equivalent of N-acetylglucosamine end groups/min at 37 degrees C). All the activity in the semen was shown to be sperm-derived, and intact spermatozoa were estimated to contain 1.23 EC units per 10(9) cells. In a low-ionic-strength medium, only some 20% of the hyaluronidase was extractable, although up to 80% of the activity could be extracted as the ionic strength was increased; further addition of detergent extracted the remainder. During purification of the enzyme, it was found that inclusion of poly(vinyl alcohol) in the media stabilized the activity; detergent inclusion also improved the yield, especially during early stages. As a consequence both of reliable quantitative determination and of stabilization, a number of forms of hyaluronidase could be isolated in high yield, by using anion-exchange chromatography, cation-exchange chromatography, affinity chromatography and gel filtration. The existence of all these forms was confirmed by electrophoresis and immunoblotting with the use of a monoclonal anti-(ram hyaluronidase) antibody, and their presence in very freshly prepared sperm extracts was demonstrated. The specific activity of the isolated major hyaluronidase form was 15.0 EC units/mg; this was equivalent to 119,000 W.H.O. units/mg, higher than any other previously reported values.
Animal models of Huntington's disease. (2006)

Huntington's disease is an autosomal dominantly inherited progressive neurodegenerative disorder. The main symptoms are choreiform, involuntary movements, personality changes and dementia. Huntington's disease is a member of a group of diseases caused by CAG repeat expansions. One research aim is to determine the earliest molecular changes associated with Huntington's disease. There is no possibility for this in humans, but various early changes have been identified in an animal model of Huntington's disease. They are constructed by excitotoxin causing striatal lesion, or mitochondrial toxins inducing energy impairment, or by generating transgenic mice.
Memory of chirality: enantioselective alkylation reactions at an asymmetric carbon adjacent to a carbonyl group (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMemory of chirality: enantioselective alkylation reactions at an asymmetric carbon adjacent to a carbonyl groupTakeo Kawabata, Kiyoshi Yahiro, and Kaoru FujiCite this: J. Am. Chem. Soc. 1991, 113, 25, 9694–9696Publication Date (Print):December 1, 1991Publication History Published online1 May 2002Published inissue 1 December 1991https://doi.org/10.1021/ja00025a057RIGHTS & PERMISSIONSArticle Views1598Altmetric-Citations130LEARN 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 (388 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Intrafamilial Clustering ofHelicobacter pyloriInfection (1990)

Colonization of the gastric antrum by Helicobacter pylori (formerly Campylobacter pylori) has been associated with primary gastritis. We determined the frequency of colonization by H. pylori in gastric-antrum biopsy specimens from 93 children undergoing gastroscopy for the evaluation of upper gastrointestinal symptoms. We also determined H. pylori IgG antibody levels by enzyme-linked immunosorbent assay in coded serum samples from these children, family members, and control subjects of comparable ages. Among 27 children with primary, or unexplained, gastritis, H. pylori was identified by silver staining in 24 biopsy specimens and by culture in 22; specific antibodies were present in 23 children (96 percent). Three children with unexplained gastritis had no evidence of H. pylori in the antrum, nor did any of 13 children with secondary gastritis or any of 53 children with normal antral histologic features; specific antibodies were present in only 1 of these 69 children. H. pylori antibody was detected in 25 of 34 parents of colonized children, but in only 8 of 33 parents of noncolonized children (P less than 0.001). Of 22 siblings of children colonized by H. pylori, 18 had specific antibodies, as compared with only 5 of 37 controls (P less than 0.001). We conclude that H. pylori-specific IgG antibodies are associated with bacterial colonization of the gastric antrum by this organism. The intrafamilial clustering of H. pylori infection suggests that there may be person-to-person spread of these bacteria.