gebhart/patrepeval huggingface dataset:
Vertical Focusing Device Utilizing Dielectrophoretic Force and Its Application on Microflow Cytometer (2004)

Focusing of particles/cells in the vertical direction inside a micromachined flow cytometer is a critical issue while using an embedded optical detection system aligned with microchannels. Even if the particles/cells have been focused centrally in the horizontal direction using coplanar sheath flows, appreciable errors may still arise if they are randomly distributed in the vertical direction. This work presents a vertical focusing device utilizing dielectrophoretic (DEP) forces and its application on micromachined flow cytometer. A pair of parallel microelectrodes is deposited on the upper and bottom surface of the microfluidic channel to drive particles/cells into the vertical center of the sample flow. This new microfluidic device is capable of three-dimensional (3-D) focusing of microparticles/cells and thus improves the uniformity of the optical detection signals. This 3-D focusing feature of the sample flow is realized utilizing the combination of dielectrophoretic and hydrodynamic forces. Initially, two sheath flows are used to focus the sample flow horizontally by means of hydrodynamic forces, and then two embedded planar electrodes apply negative DEP forces to focus the particles/cells vertically. A new micromachined flow cytometer integrated with an embedded optical detection mechanism is then demonstrated. Numerical simulation is used to analyze the operation conditions and the dimension of the microelectrodes for DEP manipulation. The dynamic trace of the moving particles/cells within a flow stream under the DEP manipulation is calculated numerically. Micro polystyrene beads and diluted human red blood cells (RBC) are used to test the performance of the proposed device. The experimental results confirm the suitability of the proposed device for applications requiring precise counting of particles or cells. Experimental data indicates the proposed method can provide more stable signals over the other types of micromachined flow cytometers that were previously reported.
Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes (2003)

Incretins are peptide hormones, exemplified by glucose-dependent insulinotropic peptide and glucagon-like peptide 1 that are released from the gut in response to nutrient ingestion and enhance glucose-stimulated insulin secretion. Incretin action is terminated due to N-terminal cleavage of the peptides by the aminopeptidase dipeptidyl peptidase IV (DPP-IV). Hence, inhibition of glucose-dependent insulinotropic peptide and glucagon-like peptide 1 degradation via reduction of DPP-IV activity represents an innovative strategy for enhancing incretin action in vivo. This review summarises the biology of incretin action, the structure, expression and pleiotropic biological activities of DPP-IV and provides an overview of the rationale, potential merits and theoretical pitfalls in the development of DPP-IV inhibitors for the treatment of type 2 diabetes.
ChemInform Abstract: Regioselective Synthesis of Substituted and Fused Pyrazolo(1,5‐a) pyrimidines as Leishmanicides. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Cluster-based text categorization (1995)

Article Cluster-based text categorization: a comparison of category search strategies Share on Authors: Makoto Iwayama Advanced Research Laboratory, Hitachi Ltd., Hatoyama, Saitama 350-03, Japan Advanced Research Laboratory, Hitachi Ltd., Hatoyama, Saitama 350-03, JapanView Profile , Takenobu Tokunaga Department of Computer Science, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro, Tokyo 152, Japan Department of Computer Science, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro, Tokyo 152, JapanView Profile Authors Info & Claims SIGIR '95: Proceedings of the 18th annual international ACM SIGIR conference on Research and development in information retrievalJuly 1995 Pages 273–280https://doi.org/10.1145/215206.215371Online:01 July 1995Publication History 63citation1,299DownloadsMetricsTotal Citations63Total Downloads1,299Last 12 Months38Last 6 weeks6 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features (2013)

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na(+)/K(+)-ATPase activity (-66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-ω3 with a consequent increase in ω6/ω3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD.
Re-Engineering Biopharmaceuticals for Delivery to Brain with Molecular Trojan Horses (2008)

Biopharmaceuticals, including recombinant proteins, monoclonal antibody therapeutics, and antisense or RNA interference drugs, cannot be developed as drugs for the brain, because these large molecules do not cross the blood-brain barrier (BBB). Biopharmaceuticals must be re-engineered to cross the BBB, and this is possible with genetically engineered molecular Trojan horses. A molecular Trojan horse is an endogenous peptide, or peptidomimetic monoclonal antibody (mAb), which enters brain from blood via receptor-mediated transport on endogenous BBB transporters. Recombinant neurotrophins, single chain Fv antibodies, or therapeutic enzymes may be re-engineered as IgG fusion proteins. The engineering of IgG-avidin fusion proteins enables the BBB delivery of biotinylated drugs. The IgG fusion proteins are new chemical entities that are dual or triple function molecules that bind multiple receptors. The fusion proteins are able both to enter the brain, by binding an endogenous BBB receptor, and to induce the desired pharmacologic effect in brain, by binding target receptors in the brain behind the BBB. The development of molecular Trojan horses for BBB drug delivery allows the re-engineering of biopharmaceuticals that, owing to the BBB problem, could not otherwise be developed as new drugs for the human brain.
Second-generation high-throughput forward genetic screen in mice to isolate subtle behavioral mutants (2011)

Forward genetic screens have been highly successful in revealing roles of genes and pathways in complex biological events. Traditionally these screens have focused on isolating mutants with the greatest phenotypic deviance, with the hopes of discovering genes that are central to the biological event being investigated. Behavioral screens in mice typically use simple activity-based assays as endophenotypes for more complex emotional states of the animal. They generally set the selection threshold for a putative mutant at 3 SDs (z score of 3) from the average behavior of normal animals to minimize false-positive results. Behavioral screens using a high threshold for detection have generally had limited success, with high false-positive rates and subtle phenotypic differences that have made mapping and cloning difficult. In addition, targeted reverse genetic approaches have shown that when genes central to behaviors such as open field behavior, psychostimulant response, and learning and memory tasks are mutated, they produce subtle phenotypes that differ from wild-type animals by 1 to 2 SDs (z scores of 1 to 2). We have conducted a second-generation (G2) dominant N-ethyl-N-nitrosourea (ENU) screen especially designed to detect subtle behavioral mutants for open field activity and psychostimulant response behaviors. We successfully detect mutant lines with only 1 to 2 SD shifts in mean response compared with wild-type control animals and present a robust statistical and methodological framework for conducting such forward genetic screens. Using this methodology we have screened 229 ENU mutant lines and have identified 15 heritable mutant lines. We conclude that for screens in mice that use activity-based endophenotypic measurements for complex behavioral states, this G2 screening approach yields better results.
The values and principles underlying the 1993 Constitution (1994)

*This is a revised version of the paper delivered at the conference 'Towards a new Constitution', held by the VerLoren van Themaat Centre for Public Law Studies, University of South Africa, 28 to 29 March 1994.
Parallel computing method for intermodal shipping network design (2012)

This study aims to improve the efficiency of design technique for intermodal shipping network design, by virtue of parallel computing system. The existing methods for maritime liner shipping network design are mainly dealing with port-to-port demand. However, a big portion of the customers of a liner shipping company locate in the inland part. Thus, a holistic analysis is necessary to deal with the inland OD pairs, where the transport mode-change from inland transportation to maritime shipping is involved. This paper first reviews a solution method for the conversion of inland OD demand to port-to-port demand. Due to the size of the global shipping network, the computational burden of solving this method is quite intensive. Hence, this paper proposes a framework for parallel computing approaches to accelerate the computation speed.
Fermentation of Propionibacterium acnes, a Commensal Bacterium in the Human Skin Microbiome, as Skin Probiotics against Methicillin-Resistant Staphylococcus aureus (2013)

Bacterial interference creates an ecological competition between commensal and pathogenic bacteria. Through fermentation of milk with gut-friendly bacteria, yogurt is an excellent aid to balance the bacteriological ecosystem in the human intestine. Here, we demonstrate that fermentation of glycerol with Propionibacterium acnes (P. acnes), a skin commensal bacterium, can function as a skin probiotic for in vitro and in vivo growth suppression of USA300, the most prevalent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). We also promote the notion that inappropriate use of antibiotics may eliminate the skin commensals, making it more difficult to fight pathogen infection. This study warrants further investigation to better understand the role of fermentation of skin commensals in infectious disease and the importance of the human skin microbiome in skin health.
Aversive and Appetitive Events Evoke the Release of Corticotropin-Releasing Hormone and Bombesin-Like Peptides at the Central Nucleus of the Amygdala (1998)

There is wide agreement that corticotropin-releasing hormone (CRH) systems within the brain are activated by stressful stimuli. There is also mounting evidence for the role of bombesin (BN)-like peptides in the mediation of the stress response. To date, however, the extent to which other stimuli increase the activity of these peptidergic systems has received little attention. In the present investigation we validated and used in vivo microdialysis sampling followed by ex vivo radioimmunoassays to monitor the release of CRH and BN-like peptides during appetitive (food intake) and stressful (restraint) events. It is demonstrated for the first time that the in vivo release of CRH and BN-like peptides at the central nucleus of the amygdala was markedly increased by both stressor exposure and food ingestion. In fact, the meal-elicited rise of CRH release was as great as that associated with 20 min of restraint stress. Paralleling these findings, circulating ACTH and corticosterone levels were also increased in response to both food intake and restraint. Contrary to the current views, these results indicate that either food ingestion is interpreted as a "stressful" event by certain neural circuits involving the central amygdala or that the CRH- and BN-related peptidergic systems may serve a much broader role than previously envisioned. Rather than evoking feelings of fear and anxiety, these systems may serve to draw attention to events or cues of biological significance, such as those associated with food availability as well as those posing a threat to survival.
Inhibition of Hsp72-Mediated Protein Refolding by 4-Hydroxy-2-nonenal (2004)

A proteomic approach was applied to liver cytosol from rats fed a diet consisting of high fat and ethanol to identify 4-hydroxy-2-nonenal (4-HNE)-modified proteins in vivo. Cytosolic Hsp72, the inducible variant of the Hsp70 heat shock protein family, was consistently among the proteins modified by 4-HNE. Despite 1.3-fold induction of Hsp72 in the livers of ethanol-fed animals, no increase in Hsp70-mediated luciferase refolding in isolated heptocytes was observed, suggesting inhibition of this process by 4-HNE. A 50% and 75% reduction in luciferase refolding efficiency was observed in rabbit reticulocyte lysate (RRL) supplemented with recombinant Hsp72 which had been modified in vitro with 10 and 100 microM 4-HNE, respectively. This observation was accompanied by a 25% and 50% decrease in substrate binding by the chaperone following the same treatment; however, no effect on complex formation between Hsp72 and its co-chaperone Hsp40 was observed. Trypsin digest and mass spectral analysis of Hsp72 treated with 10 and 100 microM 4-HNE consistently identified adduct formation at Cys267 in the ATPase domain of the chaperone. The role of this residue in the observed inhibition was demonstrated through the use of DnaK, a bacterial Hsp70 variant lacking Cys267. DnaK was resistant to 4-HNE inactivation. Additionally, Hsp72 was resistant to inactivation by the thiol-unreactive aldehyde malondialdehyde (MDA), further supporting a role for Cys in Hsp72 inhibition by 4-HNE. Finally, the affinity of Hsp72 for ATP was decreased 32% and 72% following treatment of the chaperone with 10 and 100 microM 4-HNE, respectively. In a model of chronic alcoholic liver injury, induction of Hsp72 was not accompanied by an increase in protein refolding ability. This is likely the result of 4-HNE modification of the Hsp72 ATPase domain.
Characterization of the DA26 Gene in a Hypervariable Region of the Autographa Californica Nuclear Polyhedrosis Virus Genome (1990)

A region of the baculovirus Autographa californica nuclear polyhedrosis virus genome that is frequently found to be altered after serial passage of the virus in cell culture was characterized. Sequence analysis of this region of the genome in wild-type and mutant viruses revealed that some of the mutations affected a 675 bp open reading frame, designated DA26. The DA26 gene was disrupted both by deletion and by insertion of sequences that resembled transposable elements. Northern blot analysis of DA26 showed that it was expressed very early after infection. DA26-specific transcripts could be detected after the 1 h viral adsorption period upon infection of cultured Trichoplusia ni cells. These transcripts were mapped by nuclease protection assays. A recombinant virus was constructed in which DA26 was disrupted by insertion of the Escherichia coli lacZ gene. This virus was viable in both T. ni and Spodoptera frugiperda cells and analysis of the kinetics of protein synthesis revealed no differences between wild-type and recombinant viruses. The disruption of DA26 also did not interfere with the ability of the virus to infect T. ni or S. frugiperda larvae.
High prevalence of small intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten withdrawal (2003)

This study showed that SIBO affects most celiacs with persistence of GI symptoms after gluten withdrawal.
ChemInform Abstract: SYNTHESIS OF DEHYDROAMINO ACIDS AND DIDEHYDRODIOXOPIPERAZINES AND THEIR CONVERSION INTO α‐MERCAPTO‐α‐AMINO ACID DERIVATIVES (1981)

Abstract Ausgehend von den α‐Oximinoestern (I) werden durch Reduktion, Acetylierung und DBU‐Dehydratisierung der N‐ Acety1‐Hydroxylamino‐ester (II) die ogß‐Dehydroaminosäureester (III) dargestellt.
Cytotoxic Simplified Tubulysin Analogues (2008)

An efficient route for the synthesis of the tubulysin family of antimitotic peptides was developed. Simplified tubulysin analogues were synthesized to define the minimum pharmacophore required for cytotoxicity. Simplified tubulysin analogues retain significant cytotoxicity and reveal important preliminary structure-activity relationships.
High-Density Growth of Single-Wall Carbon Nanotubes on Silicon by Fabrication of Nanosized Catalyst Thin Films (2002)

A simple method for the synthesis of metal oxide thin films through gel solutions of inorganic metal salts using poly(ethylene glycol) was developed. The technique was then applied to fabricate nanoscale MgO-supported catalysts for the surface CVD growth of single-wall carbon nanotubes (SWNTs.) The results showed that the catalytic films greatly promoted the growth of SWNTs of high quality, density, and uniformity. The bundle sizes, growth density, and orientation of the resulting SWNTs could be controlled to some extent by choosing the type of catalyst and by suitable modification of the reaction parameters.
Toward the future of psychiatric diagnosis: the seven pillars of RDoC (2013)

Future diagnostic systems cannot reflect ongoing advances in genetics, neuroscience and cognitive science until a literature organized around these disciplines is available to inform the revision efforts. The goal of the RDoC project is to provide a framework for research to transform the approach to the nosology of mental disorders.
Genetic Dissection of Complex Traits (1994)

Medical genetics was revolutionized during the 1980s by the application of genetic mapping to locate the genes responsible for simple Mendelian diseases. Most diseases and traits, however, do not follow simple inheritance patterns. Genetics have thus begun taking up the even greater challenge of the genetic dissection of complex traits. Four major approaches have been developed: linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses. This article synthesizes the current state of the genetic dissection of complex traits--describing the methods, limitations, and recent applications to biological problems.
Autochthonous liver tumors induce systemic T cell tolerance associated with T cell receptor down-modulation # (2008)

The reason the adaptive immune system fails in advanced liver tumors is largely unclear. To address this question, we have developed a novel murine model that combines c-myc-induced autochthonous tumorigenesis with expression of a cognate antigen, ovalbumin (OVA). When c-myc/OVA transgenic mice were crossed with liver-specific inducer mice, multifocal hepatocellular carcinomas co-expressing OVA developed in a tetracycline-dependent manner with a short latency and 100% penetrance. Transferred OVA-specific T cells, although infiltrating the tumor at high numbers, were hyporesponsive, as evidenced by a lack of in vivo cytotoxicity and interferon gamma production. This allowed the tumor to progress even in the presence of large numbers of antigen-specific T cells and even after vaccination (OVA+CpG-DNA). Interestingly, T cell receptor down-modulation was observed, which may explain antigen-specific hyporesponsiveness. This model is helpful in understanding liver cancer-specific mechanisms of T cell tolerance and dissection of antigen-specific and nonspecific mechanisms of immunotherapies in the preclinical phase.
Synthesis and Biological Evaluation of 8-Oxoadenine Derivatives as Toll-like Receptor 7 Agonists Introducing the Antedrug Concept (2010)

Systemic administration of a Toll-like receptor 7 (TLR7) agonist is effective to in suppressing Th2 derived inflammation, however systemic induction of various cytokines such as IL-6, IL-12, and type I interferon (IFN) is observed. This cytokine induction would be expected to cause flu-like symptoms. We have previously reported adenine compounds (3, 4) as interferon inducing agents acting as TLR7 agonists. To identify potent anti-inflammatory compounds without systemic side effects, a labile carboxylic ester as an antedrug functionality onto the N(9)-benzyl group of the adenine was introduced. We found that 9e was a potent TLR7 agonist (EC(50) 50 nM) and rapidly metabolized by human plasma (T(1/2) 2.6 min) to the pharmacologically much less active carboxylic acid 16. Intratracheal administration of 9e effectively inhibited allergen-induced airway inflammation without inducing cytokines systemically. Therefore, the TLR7 agonist with antedrug characteristics 9e (SM-324405) is a novel candidate for immunotherapy of allergic diseases.
Fatty Acids and Other Compounds with Nematicidal Activity from Cultures of Basidiomycetes (1994)

In a screening for nematicidal activities in cultures of Basidiomycetes, cultures of Pleurotus pulmonarius and Hericium coralloides exhibited toxic effects towards the saprophytic nematode Caenorhabditis elegans. Subsequently S-coriolic acid (1), linoleic acid (2), p-anisaldehyde (3), p-anisyl alcohol (4), 1-(4-methoxyphenyl)-1,2-propanediol (5), and 2-hydroxy-(4'-methoxy)-propiophenone (6) were isolated from submerged cultures of P. pulmonarius. All compounds showed nematicidal activities towards C. elegans. The most active compounds were 1 and 2 with LD50 values between 5 and 10 ppm. Compounds 1, 4, and 5 have not been previously isolated from higher fungi, 6 is a new natural product. From cultures of H. coralloides, which exhibited both repellant and nematicidal effects, a nematicidal fatty acid mixture was obtained, containing linoleic acid, oleic acid, and palmitic acid as its main components.