gebhart/patrepeval huggingface dataset:
Transepithelial Transport of Fc-Targeted Nanoparticles by the Neonatal Fc Receptor for Oral Delivery (2013)

Nanoparticles are poised to have a tremendous impact on the treatment of many diseases, but their broad application is limited because currently they can only be administered by parenteral methods. Oral administration of nanoparticles is preferred but remains a challenge because transport across the intestinal epithelium is limited. We show that nanoparticles targeted to the neonatal Fc receptor (FcRn), which mediates the transport of immunoglobulin G antibodies across epithelial barriers, are efficiently transported across the intestinal epithelium using both in vitro and in vivo models. In mice, orally administered FcRn-targeted nanoparticles crossed the intestinal epithelium and reached systemic circulation with a mean absorption efficiency of 13.7%*hour compared with only 1.2%*hour for nontargeted nanoparticles. In addition, targeted nanoparticles containing insulin as a model nanoparticle-based therapy for diabetes were orally administered at a clinically relevant insulin dose of 1.1 U/kg and elicited a prolonged hypoglycemic response in wild-type mice. This effect was abolished in FcRn knockout mice, indicating that the enhanced nanoparticle transport was specifically due to FcRn. FcRn-targeted nanoparticles may have a major impact on the treatment of many diseases by enabling drugs currently limited by low bioavailability to be efficiently delivered though oral administration.
Antigen Presentation in the CNS by Myeloid Dendritic Cells Drives Progression of Relapsing Experimental Autoimmune Encephalomyelitis (2007)

Chronic progression of relapsing experimental autoimmune encephalomyelitis (R-EAE), a mouse model of multiple sclerosis (MS), is dependent on the activation of T cells to endogenous myelin epitopes, that is, epitope spreading. This review focuses on the cellular and molecular mechanisms underlying the process of epitope spreading. Surprisingly, activation of naïve T cells to endogenous myelin epitopes in SJL mice undergoing R-EAE occurs directly in the central nervous system (CNS), a site generally perceived to be immunologically privileged. Determination of the antigen presentation capacity of antigen-presenting cell (APC) populations purified from the CNS of mice with established R-EAE shows that peripherally derived CD11b(+)CD11c(+)CD45(hi) myeloid dendritic cells (mDCs) most efficiently present endogenous myelin antigens to activate both preactivated effector myelin-specific T cells and naïve T cells. The mDCs, which drive epitope spreading, preferentially polarize pathogenic Th17 responses correlating with their enhanced expression of TGF-beta1, IL-6, and IL-23. Both B220(+)CD11c(+) plasmacytoid (pDCs) and CD8alpha(+)CD11c(+) (CD8 DCs) were superior to CD11b(+)CD11c(-)CD45(hi) macrophages, but less efficient than mDCs at presenting endogenous peptide to induce Th17 cells. In contrast, CNS-resident CD11b(+)CD11c(-)CD45(low) microglia purified from the inflamed CNS were found to be largely incapable of activating either naïve or effector T cells.
The role of dietary nucleotides in neonatal and infant nutrition. (1998)

Human milk has a higher concentration of nucleotides than bovine milk which is the source of most infant formulas. As the composition of human milk is considered the 'gold standard,' an increasing number of infant formulas are supplemented with nucleotides. This review summarises the biology of human milk nucleotides and evaluates the studies which investigated the clinical benefits of feeding infants with nucleotide-supplemented formulas. Although dietary nucleotides have been suggested to have beneficial gastrointestinal and immunological effects, nucleotide-supplemented formula feeding has not been shown to confer the same benefits as breast feeding, and randomised controlled trials have yet to prove that healthy term infants fed nucleotide-supplemented formulas compared to those fed nonsupplemented formulas, have accelerated physical growth and neurological development, better growth and development of their gastrointestinal tract resulting in improved digestive and absorptive functions, enhanced development of their immune system resulting in increased resistance to infection and lower bacterial and viral infection rates during infancy, and a more favourable intestinal microflora associated with a lower rate of infectious diarrhoea. However, a randomised controlled trial has reported that term infants with severe intrauterine growth retardation do have better catch-up growth with nucleotide supplementation. The hypothesis that nucleotides are semi-essential nutrients needs to be further studied, in particular in the presence of prematurity, fetal growth retardation, intestinal injury and limited nutrient intake. As no deleterious effects have been reported with the use of nucleotide-supplemented formulas, the first of which was introduced over 30 years ago, such products are considered safe when nucleotides are supplemented to an amount equivalent to the free nucleotide concentration of human milk. More basic and clinical research studies are awaited to further define the biology and role of human milk nucleotides, and to critically assess the potential benefits and appropriate level of nucleotide supplementation of infant formula.
Metabonomics Based on NMR Spectroscopy (2004)

Understanding the chemical processes that occur in cells has captured the attention of scientists for over a century and yet work in this area has waned in the face of the 'molecular biology' revolution, until the past few years. The renaissance in this activity has arisen through the availability of techniques that allow the study of biochemical reactions in whole cells and tissues.
Isolation and Characterization of Methanomethylovorans hollandica gen. nov., sp. nov., Isolated from Freshwater Sediment, a Methylotrophic Methanogen Able To Grow on Dimethyl Sulfide and Methanethiol (1999)

A newly isolated methanogen, strain DMS1(T), is the first obligately anaerobic archaeon which was directly enriched and isolated from a freshwater sediment in defined minimal medium containing dimethyl sulfide (DMS) as the sole carbon and energy source. The use of a chemostat with a continuous DMS-containing gas stream as a method of enrichment, followed by cultivation in deep agar tubes, resulted in a pure culture. Since the only substrates utilized by strain DMS1(T) are methanol, methylamines, methanethiol (MT), and DMS, this organism is considered an obligately methylotrophic methanogen like most other DMS-degrading methanogens. Strain DMS1(T) differs from all other DMS-degrading methanogens, since it was isolated from a freshwater pond and requires NaCl concentrations (0 to 0.04 M) typical of the NaCl concentrations required by freshwater microorganisms for growth. DMS was degraded effectively only in a chemostat culture in the presence of low hydrogen sulfide and MT concentrations. Addition of MT or sulfide to the chemostat significantly decreased degradation of DMS. Transient accumulation of DMS in MT-amended cultures indicated that transfer of the first methyl group during DMS degradation is a reversible process. On the basis of its low level of homology with the most closely related methanogen, Methanococcoides burtonii (94.5%), its position on the phylogenetic tree, its morphology (which is different from that of members of the genera Methanolobus, Methanococcoides, and Methanohalophilus), and its salt tolerance and optimum (which are characteristic of freshwater bacteria), we propose that strain DMS1(T) is a representative of a novel genus. This isolate was named Methanomethylovorans hollandica. Analysis of DMS-amended sediment slurries with a fluorescence microscope revealed the presence of methanogens which were morphologically identical to M. hollandica, as described in this study. Considering its physiological properties, M. hollandica DMS1(T) is probably responsible for degradation of MT and DMS in freshwater sediments in situ. Due to the reversibility of the DMS conversion, methanogens like strain DMS1(T) can also be involved in the formation of DMS through methylation of MT. This phenomenon, which previously has been shown to occur in sediment slurries of freshwater origin, might affect the steady-state concentrations and, consequently, the total flux of DMS and MT in these systems.
The Salmonella spvB virulence gene encodes an enzyme that ADP‐ribosylates actin and destabilizes the cytoskeleton of eukaryotic cells (2001)

ADP-ribosylating enzymes, such as cholera and diphtheria toxins, are key virulence factors for a variety of extracellular bacterial pathogens but have not been implicated previously during intracellular pathogenesis. Salmonella strains are capable of invading epithelial cells and localizing in macrophages during infection. The spvB virulence gene of Salmonella is required for human macrophage cytotoxicity in vitro and for enhancing intracellular bacterial proliferation during infection. Here, we present evidence that spvB encodes an ADP-ribosylating enzyme that uses actin as a substrate and depolymerizes actin filaments when expressed in CHO cells. Furthermore, site-directed mutagenesis demonstrates that the ADP-ribosylating activity of SpvB is essential for Salmonella virulence in mice. As spvB is expressed by Salmonella strains after invasion of epithelial cells or phagocytosis by macrophages, these results suggest that SpvB functions as an intracellular ADP-ribosylating toxin critical for the pathogenesis of Salmonella infections.
Reactive poly(2-vinyl-4,4-dimethyl-5-oxazolone) and poly[(2-vinyl-4,4-dimethyl-5-oxazolone)-co-(methyl methacrylate)]s. Synthesis, characterization and chemical modification with 4-methoxy-4'-(-aminoethoxy)biphenyl (1998)

Poly(2-vinyl-4,4-dimethyl-5-oxazolone) (P0) and poly[(2-vinyl-4,4-dimethyl-5-oxazolone)-co-(methyl methacrylate)]s with increasing content of methyl methacrylate units (P1–P4) were synthesized and characterized. NMR spectra were discussed in terms of monomer sequence distribution and tacticity effects. The reaction of 4-methoxy-4′-hydroxybiphenyl (1) with 2-ethyl-2-oxazoline was utilized to prepare 4-methoxy-4′-(β-aminoethoxy)biphenyl (3) through the intermediate 4-methoxy-4′-[(N-propanoyl)-β-aminoethoxy]biphenyl (2). The homopolymer P0 and two copolymers P2 and P3 were functionalized with 4-methoxybiphenyl side groups by reaction with 3 via a ring-opening process in N,N-dimethylformamide (DMF) or 1,2-dichloroethane. The resulting copolymers P5–P8 were characterized by 1H and 13C NMR. The highest degree of functionalized units was obtained in DMF at 80°C.
Differential Antigenic Stimulation Influences Cytokine Production Patterns in T Cells and CD4+ Subpopulations (1996)

The regulatory mechanisms that govern the commitment of T cells to a Th1 or Th2 lineage in terms of cytokine production patterns have not yet been fully elucidated. The authors have endeavored to study the role of the antigen in regulating the production of cytokines. To study this matter, a panel of antigens was chosen to include two random poly amino acids, PA1 (Poly(1-Phe, L-Glu)Poly-dL-Ala-PolyL-Lys), PA2 (Poly(Glu-NaAla), and two purified protein derivatives PPD1 (H37Rv virulent) and PPD2 (H37Ra non-virulent) obtained from WHO strains of Mycobacterium tuberculosis. After in vivo priming, murine spleen cells were prepared and three groups of cells (unfractionated, T cells, and CD4+ populations) were each separately stimulated in vitro with the original antigen Staphylococcal enterotoxin B (SEB) and phorbol myristate acetate (PMA). ELISA assays were subsequently performed on supernatants for IL-4, IL-5, IL-2 and IFN-g. The results indicate a different cytokine pattern for the various antigenic stimulations. The PPD1 induced IL-5 production, while the PPD2 induced high levels of IFN-gamma. SEB was shown to exert a strong effect on the cytokine profile shifting it towards a Th1-like profile. A comparison is made between the cytokine patterns in different cells. The role of antigens and superantigens in regulating cytokine production and determining the outcome of the pathological process in relation to other regulatory factors is discussed.
Classification of hepatitis C viruses based on phylogenetic analysis of the envelope 1 and nonstructural 5B regions and identification of five additional subtypes. (1994)

Genotyping of hepatitis C virus-positive sera by means of a line probe assay indicated that < 3% of European samples, but up to 30% of Gabonese sera, could not be classified as either 1a, 1b, 2a, 2b, 3a, 3b, 4c, 5a, or 6a. Such samples were analyzed in the 5' untranslated region and in the nonstructural 5 (NS5) region. Classification based on phylogenetic analysis of the commonly used 222-bp-long NS5B region was possible for most but not all of the selected sera. Therefore, the core/envelope 1 region (579 bp) and a larger NS5B (340 bp) region were also analyzed. Only the phylogenetic analysis of the 340-bp NS5B region of these newly identified and published isolates provided unambiguous classification into types and subtypes. Furthermore, unequivocal evidence for four subtypes in type 2 and eight subtypes in type 4 was provided. A specific recognition sequence in the 5' untranslated region was observed for every newly identified subtype. Based on 1830 pair-wise comparisons in NS5B, isolates belonging to the same subtype showed evolutionary distances of < 0.127 and isolates of the same type exhibited evolutionary distances of < 0.328. These phylogenetic border distances can be conveniently used for classification of hepatitis C virus isolates into types and subtypes.
Triatlón y entrenamiento: 101 plus consejos esenciales para triatletas (2003)

Este artículo expuesto en forma de inventario, desglosa consejos que los triatletas tienen que tener en cuenta para la mejora de su rendimiento. El cuestionario ha sido diseñado de forma que el deportista o el entrenador puedan identificar los puntos que necesitan más cuidado y consideración para que no se nos pasen de largo. El inventario ha sido dividido en diferentes categorías: Carrera, natación, ciclismo, nutrición, psicología, entrenamiento general...
A novel peak power reduction scheme for OFDM (2002)

An efficient and distortionless scheme for peak power reduction in orthogonal frequency division multiplexing (OFDM) is proposed, which introduces some additional complexity but nearly vanishing redundancy. The approach is very flexible and works with arbitrary numbers of subcarriers and without restriction on the type of modulation applied in them. The core of the approach is the coordination of appropriately phase rotated signal parts to minimize the peak power of the multiplex signal. The improved statistics of peak power in the optimized transmit signal are demonstrated by simulation results. Finally, it is shown that this scheme is close to the theoretical limit curve of redundancy versus minimum peak-to-average power ratio (PAR).
Endocyclic α,β-Unsaturated Ketones. V.1 Synthesis and Reaction of 3-Bromo-1,1-dimethyl-2-keto-1,2-dihydronaphthalene with Morpholine (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEndocyclic α,β-Unsaturated Ketones. V.1 Synthesis and Reaction of 3-Bromo-1,1-dimethyl-2-keto-1,2-dihydronaphthalene with MorpholineNORMAN H. CROMWELL and RICHARD D. CAMPBELLCite this: J. Org. Chem. 1957, 22, 5, 520–523Publication Date (Print):May 1, 1957Publication History Published online1 May 2002Published inissue 1 May 1957https://pubs.acs.org/doi/10.1021/jo01356a013https://doi.org/10.1021/jo01356a013research-articleACS PublicationsRequest reuse permissionsArticle Views208Altmetric-Citations8LEARN 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
Environmental Modeling for Automated Cloud Application Testing (2011)

Platforms such as Windows Azure let applications conduct data-intensive cloud computing. Unit testing can help ensure high-quality development of such applications, but the results depend on test inputs and the cloud environment's state. Manually providing various test inputs and cloud states is laborious and time-consuming. However, automated test generation must simulate various cloud states to achieve effective testing. To address this challenge, a proposed approach models the cloud environment and applies dynamic symbolic execution to generate test inputs and cloud states. Applying this approach to open-source Azure cloud applications shows that it can achieve high structural coverage.
Implantation of dispersed cells into primate brain (1989)

Although several experimental therapies such as dopaminergic cell implantation in parkinsonian models and intratumoral placement of lymphokine-activated killer cells require intracerebral deposition of dispersed cell suspensions, a successful technique of needle implantation of cells into primate brain has not been demonstrated. The authors have sought to establish a stereotaxic technique to predictably deposit dispersed cells in primate brain. Human lymphocytes were cultured in recombinant interleukin-2, labeled with sodium 51 chromate (51Cr), and stereotaxically injected into the frontal white matter of six anesthetized rhesus monkeys. A 10-microliters aliquot of cell suspension (2 X 10(7) cells/ml) was deposited 16 mm deep to the dura at 5 microliters/min via Hamilton No. 22s or 26s needles. Five control aliquots were counted for each injection. Reflux out of the needle track was absorbed on gauze, and the recovered cells were counted. The animals were sacrificed 1 hour after implantation and the brain was removed and sectioned such that the cortex and white matter along the needle track were separate. The tissue sections were then counted. Recovery was expressed as the percentage of total injected radioactivity (cpm) that was present in each brain section. Two additional injected hemispheres were processed for autoradiography and histological study. Cell recovery in the brain (mean +/- standard deviation) was 87.2% +/- 13.9% (3.3% +/- 4.9% in cortex and 83.9% +/- 15.9% in white matter). The autoradiograms and histological examination showed a dense accumulation of radioactivity (cells) at the target site and minimal radioactivity (cells) in the needle track. Accurate intracerebral deposition of dispersed cells in primates was achieved with the technique described. This knowledge permits reliable stereotaxic implantation of cells into the brains of nonhuman primates and humans for investigation and therapy.
T-CELL DERIVED LYMPHOKINES AS REGULATORS OF CHRONIC INFLAMMATION (1996)

In recent years, compelling evidence has accumulated that inflammation results from a cascade of events that are orchestrated by cytokines. Cytokines are products of nonimmune and immune cells which regulate the recruitment, differentiation, and proliferation of inflammatory cells. Although there is redundancy in cytokine production and function, major pathways of cytokines have been identified. Besides macrophages, T cells represent important sources of pro- and anti-inflammatory cytokines. In support of a critical regulatory role of T cells in inflammation, two T cell subtypes characterized by different cytokine profiles have been described. TH1 cells produce interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and are prone to interact with macrophages. TH2 cells are producers of IL-4, IL-5, and IL-10 and are capable of supporting B cells and eosinophils. Here, we are providing evidence that different human inflammatory diseases are characterized by distinct in situ cytokine patterns. Giant cell vasculitis represents a typical TH1-like disease, whereas TH2 helper cells appear to be more important in rheumatoid arthritis. Given the association of different diseases with cytokine profiles, the question arises how the microenvironment influences cytokine pattern and thus disease and whether mediators produced at the site of inflammation could serve as therapeutic targets to modulate the cytokine cascade. Prostaglandin E(2) (PGE(2)) is an important inflammatory mediator. We have examined the influence of PGE(2) and the PGE analog misoprostol on T-cell function and T-cell cytokine production. Here, we describe that IL-2 and IFN-gamma production are sensitive to PGE(2) and misoprostol, whereas IL-4 and IL-5 are unaffected. Thus, in the presence of PGE(2), TH0 cells acquire a TH2-like function, whereas TH1-like aspects are suppressed. We suggest that PGE(2) and misoprostol might represent useful modulators of the cytokine network.
Heat-shock proteins protect cells from monocyte cytotoxicity: possible mechanism of self-protection. (1993)

We have previously shown that major heat-shock protein (hsp 70) protects WEHI-S tumor cells from cytotoxicity mediated by tumor necrosis factor alpha (TNF-alpha) and TNF-beta. In the present study, the effect of altered expression of hsp70 and low molecular weight heat-shock protein, hsp27, on tumor cell sensitivity to monocytes and lymphokine-activated killer (LAK) cells was studied. Constitutive and stable expression of transfected human hsp70 rendered cells almost completely resistant to monocytes. Conversely, inhibition of endogenous hsp70 by expression of antisense hsp70 RNA enhanced the sensitivity of cells to monocyte-mediated killing. Surprisingly, overexpression of human hsp27, which does not protect WEHI-S cells from TNF killing, conferred partial resistance to monocytes. Only approximately 60% of monocyte-mediated killing of WEHI-S cells could be blocked by neutralizing TNF-alpha antibody or immunoglobulin G-TNF receptor chimeric protein, suggesting the presence of both TNF-dependent and TNF-independent lytic mechanisms. As free radicals have been suggested to be mediators of monocyte cytotoxicity, we tested the sensitivity of transfected cells to oxidative stress. Overexpression of either hsp70 or hsp27 rendered cells partially resistant to hydrogen peroxide. No significant changes in the susceptibility of cell lines overexpressing hsp70 or hsp27 to cytotoxicity mediated by LAK cells were observed. Interestingly, monocytes but not LAK cells contained detectable levels of hsp27 and hsp70 in nonstressed conditions. Taken together, these data indicate that hsp70 protects tumor cells from TNF-mediated monocyte cytotoxicity and that both hsp27 and hsp70 confer resistance to TNF-independent, probably free radical-mediated lysis by monocytes. Moreover, hsp27 and hsp70 may provide monocytes with a protective mechanism against their own toxicity.
Tramadol Added to Lidocaine for Intravenous Regional Anesthesia (2001)

Tramadol, a centrally acting analgesic, might have local anesthetic properties, as do some opioid drugs. We demonstrated that 0.25% tramadol solution containing 100 mg tramadol is not effective as a sole drug, but may improve the action of 0.5% lidocaine for intravenous regional anesthesia. The increased incidence of side effects may limit the clinical use of tramadol.