gebhart/patrepeval huggingface dataset:
pH-Responsive Nanoparticle Vaccines for Dual-Delivery of Antigens and Immunostimulatory Oligonucleotides (2013)

Protein subunit vaccines offer important potential advantages over live vaccine vectors but generally elicit weaker and shorter-lived cellular immune responses. Here we investigate the use of pH-responsive, endosomolytic polymer nanoparticles that were originally developed for RNA delivery as vaccine delivery vehicles for enhancing cellular and humoral immune responses. Micellar nanoparticles were assembled from amphiphilic diblock copolymers composed of an ampholytic core-forming block and a redesigned polycationic corona block doped with thiol-reactive pyridyl disulfide groups to enable dual-delivery of antigens and immunostimulatory CpG oligodeoxynucleotide (CpG ODN) adjuvants. Polymers assembled into 23 nm particles with simultaneous packaging of CpG ODN and a thiolated protein antigen, ovalbumin (ova). Conjugation of ova to nanoparticles significantly enhanced antigen cross-presentation in vitro relative to free ova or an unconjugated, physical mixture of the parent compounds. Subcutaneous vaccination of mice with ova-nanoparticle conjugates elicited a significantly higher CD8(+) T cell response (0.5% IFN-γ(+) of CD8(+)) compared to mice vaccinated with free ova or a physical mixture of the two components. Significantly, immunization with ova-nanoparticle conjugates electrostatically complexed with CpG ODN (dual-delivery) enhanced CD8(+) T cell responses (3.4% IFN-γ(+) of CD8(+)) 7-, 18-, and 8-fold relative to immunization with conjugates, ova administered with free CpG, or a formulation containing free ova and CpG complexed to micelles, respectively. Similarly, dual-delivery carriers significantly increased CD4(+)IFN-γ(+) (Th1) responses and elicited a balanced IgG1/IgG2c antibody response. Intradermal administration further augmented cellular immune responses, with dual-delivery carriers inducing ∼7% antigen-specific CD8(+) T cells. This work demonstrates the ability of pH-responsive, endosomolytic nanoparticles to actively promote antigen cross-presentation and augment cellular and humoral immune responses via dual-delivery of protein antigens and CpG ODN. Hence, pH-responsive polymeric nanoparticles offer promise as a delivery platform for protein subunit vaccines.
β-PEPTIDES: NATURE IMPROVED? (1997)

RETURN TO ISSUEPREVNewsNEXTβ-PEPTIDES: NATURE IMPROVED?Peptide analogs from β-amino acids fold into defined three-dimensional structures similar to those of natural peptidesSTU BORMANView Author Information C&EN WashingtonCite this: Chem. Eng. News 1997, 75, 24, 32–35Publication Date (Print):June 16, 1997Publication History Published online12 November 2010Published inissue 16 June 1997https://doi.org/10.1021/cen-v075n024.p032Copyright © 1997 American Chemical SocietyArticle Views20Altmetric-Citations6LEARN 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 (1 MB) SUBJECTS:Antineoplastic agents,Oligomers,Peptides and proteins,Reaction products Get e-Alerts
Innate immune signaling by Toll-like receptor-4 (TLR4) shapes the inflammatory microenvironment in colitis-associated tumors (2009)

These findings indicate that TLR4 signaling on CEC is necessary for recruitment and activation of Cox-2-expressing macrophages and increasing the number and size of dysplastic lesions. Our results implicate innate immune signaling on CEC as a key regulator of a tumor-promoting microenvironment.
Using case-based retrieval for customer technical support (1992)

Cascade, a case-based interactive system that helps technical support engineers solve the problems of customers whose hardware or software has stopped working, is discussed. Cascade has a case library of failures of VMS device drivers and suggests solutions to new failures. The system uses validated retrieval to address aspects of failure recovery that are specific to help desks. Cascade's implementation, which was accomplished by developing a seed case base, a knowledge base containing knowledge about similarities between surface-feature values, and a validation model containing the necessary probes and knowledge about them, is described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A unique gene expression signature discriminates familial Alzheimer's disease mutation carriers from their wild-type siblings (2005)

Alzheimer's disease (AD) is a neurodegenerative disease with an insidious onset and progressive course that inevitably leads to death. The current diagnostic tools do not allow for diagnosis until the disease has lead to irreversible brain damage. Genetic studies of autosomal dominant early onset familial AD has identified three causative genes: amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2). We performed a global gene expression analysis on fibroblasts from 33 individuals (both healthy and demented mutation carriers as well as wild-type siblings) from three families segregating the APP(SWE), APP(ARC) and PSEN1 H163Y mutations, respectively. The mutations cause hereditary progressive cognitive disorder, including typical autosomal dominant AD. Our data show that the mutation carriers share a common gene expression profile significantly different from that of their wild-type siblings. The results indicate that the disease process starts several decades before the onset of cognitive decline, suggesting that presymptomatic diagnosis of AD and other progressive cognitive disorders may be feasible in the near future.
Intracellular Cl- activity and cellular Cl- pathways in cultured human airway epithelium (1989)

Cl- transport was studied in human nasal epithelium, a predominantly Na+-absorbing proximal airway epithelium. Intracellular Cl- activity (aClc) and the electrical potentials across the apical (Va) and basolateral (Vb) membranes were measured with double-barreled, Cl- -selective microelectrodes to characterize the driving forces for Cl- flow across each membrane. Under control conditions (bilateral Krebs-bicarbonate Ringer), Va was -26.1 +/- 1.2 mV, Vb was -36.2 +/- 1.2 mV, and aCL(c) was 42.7 +/- 2.0 mM (n = 34), indicating that Cl- is near electrochemical equilibrium across the apical membrane but significantly above equilibrium across the basolateral membrane. Reduction of luminal [Cl-] from 120 to 3 mM reduced aClc from 42.7 +/- 4.0 to 27.0 +/- 3.5 mM, depolarized Va, and increased fractional apical membrane resistance (fRa) and transepithelial resistance (Rt). Serosal bumetanide reduced aClc by 10 mM without affecting electrical parameters. Reduction of serosal [Cl-] from 120 to 3 mM resulted in a rapid decrease in Vb, a decrease in fRa and an increase in Rt. Also, serosal [Cl-] reduction led to a slow decrease in aClc rom 45.5 +/- 2.5 to 31.1 +/- 4.2 mM) that could be inhibited by bumetanide. The data are consistent with the following conclusions: 1) Cl- is transported across the apical membrane through a conductive pathway; and 2) Cl- is translocated across the basolateral membrane by an electrically silent bumetanide-sensitive cotransport system and by a minor conductive path.
The Thrombogenic Effect of Anticancer Drug Therapy in Women with Stage II Breast Cancer (1988)

Thromboembolic disease has long been recognized as a complication of cancer. Recent reports have suggested that drugs used in the treatment of cancer, including chemotherapeutic agents and hormones, may contribute to this risk, but it has not been possible to separate the effect of these drugs from that of the cancer. We performed a randomized trial comparing 12 weeks of chemohormonal therapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, doxorubicin, and tamoxifen) with 36 weeks of chemotherapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone) in patients with Stage II breast cancer. Among 205 patients randomly assigned to treatment, there were 14 episodes of thrombosis (6.8 percent). These 14 episodes occurred during 979 patient-months of chemotherapy; by comparison, there were no events during 2413 patient-months without therapy. During the first 12 weeks of the study, five patients in the 12-week group and four patients in the 36-week group had thrombosis. During the subsequent 24 weeks, when only patients in the 36-week group were still receiving chemotherapy, there was no thrombosis in the 12-week group, but there were five additional events in the 36-week group (P = 0.03). These findings suggest that chemotherapy contributes to thrombosis in patients with breast cancer.
Reduced instruction set computers (1985)

Reduced instruction set computers aim for both simplicity in hardware and synergy between architectures and compilers. Optimizing compilers are used to compile programming languages down to instructions that are as unencumbered as microinstructions in a large virtual address space, and to make the instruction cycle time as fast as possible.
Towards a mutation-based automatic framework for evaluating code clone detection tools (2008)

In the last decade, a great many code clone detection tools have been proposed. Such a large number of tools calls for a quantitative comparison, and there have been several attempts to empirically evaluate and compare many of the state-of-the-art tools. However, a recent study shows that there are several factors that could influence the the validity of the results of such comparisons. In order to overcome the effects of such factors (at least in part), in this student poster paper we outline a mutation-based controlled frame-work for evaluating clone detection tools using edit-based mutation operators that model cloning actions. While the framework is not yet completely implemented and as yet we do not have experimental data, we anticipate that such a framework will provide a useful contribution to the community by providing a more solid objective foundation for tool evaluation.
Immune Complex/Ig Negatively Regulate TLR4-Triggered Inflammatory Response in Macrophages through FcγRIIb-Dependent PGE2 Production (2009)

Excessive activation of TLR may induce endotoxin shock and inflammatory diseases, so the negative regulation of TLR-triggered inflammatory response attracts much attention. Nonpathogenic immune complex (IC) and Ig (IC/Ig) have been shown to play important roles in the regulation of immune responses and to be therapeutic in some kinds of autoimmune diseases. However, the role of IC/Ig in the regulation of TLR-triggered inflammatory responses and the underlying mechanisms remain to be fully understood. In this study we demonstrate that IC/Ig can significantly inhibit LPS-induced secretion of TNF-alpha and IL-6 from macrophages by preferentially inducing PGE(2). Pretreatment of mice with IC can protect wild-type mice, but not Fc gammaRIIb(-/-) mice, from lethal endotoxin shock, and significantly reduce the levels of serum TNF-alpha and IL-6 in wild-type mice but not in Fc gammaR IIb(-/-) mice. Furthermore, blockade of PGE(2) by celecoxib restores LPS-induced production of TNF-alpha and IL-6 in the presence of IC both in vitro and in vivo. Accordingly, blockade of PGE(2) production in vivo results in the increased sensitivity of IC-pretreated mice to lethal endotoxin shock. Therefore, IC/Ig can negatively regulate TLR4-triggered inflammatory response in macrophages through Fc gammaRIIb-dependent PGE(2). In addition, our results suggest that down-regulation of NF-kappaB activation and TLR4 expression but activation of protein kinase A pathway in macrophages by IC/Ig contribute to the negative regulatory process. Thus we provide new manner for the immune regulation and mechanistic explanation for nonpathogenic IC/Ig in the treatment of inflammatory or autoimmune diseases.
Advanced sequencing technologies and their wider impact in microbiology (2007)

In the past 10 years, microbiology has undergone a revolution that has been driven by access to cheap high-throughput DNA sequencing. It was not long ago that the cloning and sequencing of a target gene could take months or years, whereas now this entire process has been replaced by a 10 min Internet search of a public genome database. There has been no single innovation that has initiated this rapid technological change; in fact, the core chemistry of DNA sequencing is the same as it was 30 years ago. Instead, progress has been driven by large sequencing centers that have incrementally industrialized the Sanger sequencing method. A side effect of this industrialization is that large-scale sequencing has moved out of small research labs, and the vast majority of sequence data is now generated by large genome centers. Recently, there have been advances in technology that will enable high-throughput genome sequencing to be established in research labs using bench-top instrumentation. These new technologies are already being used to explore the vast microbial diversity in the natural environment and the untapped genetic variation that can occur in bacterial species. It is expected that these powerful new methods will open up new questions to genomic investigation and will also allow high-throughput sequencing to be more than just a discovery exercise but also a routine assay for hypothesis testing. While this review will concentrate on microorganisms, many of the important arguments about the need to measure and understand variation at the species, population and ecosystem level will hold true for many other biological systems.
Semi‐quantitative assay of D antigen site density by flow cytometric analysis (1991)

This study describes the comparative measurement of D antigen site density using a fluorescent indirect antiglobulin test (FIAT) read by flow cytometry. The test results confirmed the continuum of D antigen strength from weakest D through to R2R2 and also allowed the majority of weak D samples to be adequately distinguished from D-negative samples.
Inequality in the Legal Order: Some Further Analysis and Commentary (1981)

I challenge David Jacobs' support for the conflict model of the legal order, finding serious limitations in his cross-sectional test of the model. To avoid these limitations and to extend the scope of Jacobs' study, I (1) apply his model to four additional crimes against persons and property; (2) examine race as an additional dimension of social inequality; and (3) consider how levels of crime might influence imprisonment ratios, a factor Jacobs ignored. I find no support for the hypothesis that race is a significant determinant of state imprisonment practices. Nor do I find income inequality a significant factor in imprisonment for crimes against persons and property, except in the case of larceny.
Aptamer mediated siRNA delivery (2006)

Nucleic acids that bind to cells and are subsequently internalized could prove to be novel delivery reagents. An anti-prostate specific membrane antigen aptamer that has previously been shown to bind to prostate tumor cells was coupled to siRNAs via a modular streptavidin bridge. The resulting conjugates could be simply added onto cells without any further preparation, and were taken up within 30 min. The siRNA-mediated inhibition of gene expression was as efficient as observed with conventional lipid-based reagents, and was dependent upon conjugation to the aptamer. These results suggest new venues for the therapeutic delivery of siRNAs and for the development of reagents that can be used to probe cellular physiology.
Same behaviours, different reasons: what do patients with co-occurring anorexia and autism want from treatment? (2019)

Research suggests that up to one in four individuals with anorexia nervosa (AN) may be on the autistic spectrum, and that these autistic traits may not have been recognized or diagnosed prior to eating disorder (ED) treatment. Significantly, these heightened autistic traits are associated with poorer treatment outcomes, suggesting that treatment may need to be adapted for this population. The purpose of this study was to explore with people with AN on the autistic spectrum their experiences of ED treatment, and their views on what needs to be changed. Women with AN (<i>n=</i> 13), either with an autism diagnosis or presenting with clinically significant levels of autistic traits, were interviewed on their experiences of treatment and potential improvements. Interviews were analysed using thematic analysis. The findings suggest that this population experience unique needs associated with their autism that are not being met by standard ED treatments, and recommendations are made for potential future adaptations. Future research into a more systematic approach for treatment adaptations for this population, including education programmes for clinicians, could potentially lead to better treatment experiences.
Speech and Language Processing, 2nd Edition (2008)

Dextran 70 and enoxaparin appeared to be equally effective in decreasing fibrinogen and platelet uptake in the grafts. Their combination was not significantly more effective although there was a favourable trend.
Formal Asymmetric Biocatalytic Reductive Amination (2008)

All for one: A combination of three biocatalysts (ω-transaminase, alanine dehydrogenase, and an enzyme such as formate dehydrogenase for cofactor recycling) catalyze a cascade to achieve the asymmetric transformation of a ketone into a primary α-chiral unprotected amine through a formal stereoselective reductive amination (see scheme). Only ammonia and the reducing agent (formate) are consumed during this reaction.
Efficient expression in insect cells of a soluble, active human insulin receptor protein-tyrosine kinase domain by use of a baculovirus vector (1988)

The human insulin receptor (IR) is a transmembrane glycoprotein, whose cytoplasmic domain contains an insulin-activated protein-tyrosine kinase (EC 2.7.1.112). By the use of an appropriately engineered baculovirus expression vector, a soluble cytoplasmic derivative of this domain was expressed in the insect cell line Spodoptera frugiperda (Sf9). At 24 to 48 h after Sf9 cells were infected with recombinant virus, a protein of the size expected for this domain (approximately 48 kilodaltons) constituted a major band when total cell lysates of metabolically labeled cells were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. This protein (designated AchIRPTK) was immunoprecipitated by three monoclonal antibodies, each of which recognizes a distinct antigenic site of the IR cytoplasmic domain and requires the native structure of the protein for recognition and one of which binds at or near the physiologically relevant site(s) of IR autophosphorylation. In vivo, AchIRPTK was phosphorylated on both tyrosine and serine residues. When affinity purified, the kinase was active in vitro; it autophosphorylated exclusively on tyrosine residues, and phosphorylated the exogenous substrates histone H2b and poly(Glu-Tyr). The expression of an active IR protein-tyrosine kinase molecule in this heterologous cell system provides an efficient experimental method for producing this domain in quantity for enzymatic and structural studies.
Experiments with automated protein crystallization (1987)

A liquid handling system for setting up crystallization experiments by the hanging-drop technique has been developed. The system, organized about a pipetting station and multiport rotary valve under computer control, increases the speed at which experiments can be set up and facilitates systematic studies of protein crystallization. The system is described and results of crystallization trials on 14 proteins are reported.
Factors Affecting Immunogenic Activity of Mycobacterial Ribosomal and Ribonucleic Acid Preparations (1969)

By following careful procedures, mycobacterial ribosomal fractions and ribonucleic acid (RNA) prepared by ethyl alcohol precipitation were obtained which have immunogenic activities similar to the viable attenuated H37Ra cells of Mycobacterium tuberculosis from which they were obtained. This comparison was based on the amount of ribonucleic acid (RNA) present. These preparations consisted of approximately 63% RNA and 37% protein; no deoxyribonucleic acid or polysaccharide was detected by chemical tests. A high correlation was found between the immunogenic activity of a preparation and the per cent increase in hyperchromicity at 260 nm of a ribonuclease-hydrolyzed portion. Final concentrations of sodium dodecyl sulfate higher than 0.25% when used for the preparation of the ribosomal fractions and RNA resulted in significantly lower immune responses and greater variation between experiments. This was not related to the amount of protein present. The stability of the ribosomal and RNA preparations was tested under a variety of conditions. The need for a good protective adjuvant again was shown since mouse serum readily hydrolyzed the RNA. Equal immunity was obtained after immunization by the intraperitoneal and subcutaneous routes; however, no immune response was obtained when the intravenous route was used. Preliminary results with RNA prepared with phenol showed that it was more easily degraded during preparation. This resulted in a lower immune response than was obtained with the RNA prepared with ethyl alcohol.
Regulation of gene expression by insulin (1996)

While insulin has long been known to modulate intracellular metabolism by altering the activity or intracellular location of various enzymes, it is only in the past 10 years that the regulation of gene expression by insulin has been recognized as a major action of this hormone. This review principally focuses on the regulation of gene transcription by insulin, although recent progress in the understanding of insulin-regulated mRNA stability and translation is also summarized. The identification of cis-acting elements and associated trans-acting factors through which insulin either increases or decreases the transcription of specific genes is reviewed in detail. Recent advances in the understanding of the mechanisms of insulin signaling are discussed in the context of insulin-regulated gene transcription, and emphasis is placed on the gaps that remain between the upstream signaling molecules and the downstream trans-acting factors whose binding/transactivation potential is ultimately regulated. Finally, potential gene expression defects that may contribute to the pathophysiology of non-insulin-dependent diabetes mellitus and hypertriglyceridemia are considered.
RESTRICTION AND MODIFICATION SYSTEMS (1991)

Orthologs and paralogs are two fundamentally different types of homologous genes that evolved, respectively, by vertical descent from a single ancestral gene and by duplication. Orthology and paralogy are key concepts of evolutionary genomics. A ...Read More