gebhart/patrepeval huggingface dataset:
Regulation of mucosal and systemic antibody responses by T helper cell subsets, macrophages, and derived cytokines following oral immunization with live recombinant Salmonella (1996)

We have assessed regulatory Th cell and cytokine responses in mice after oral immunization with recombinant Salmonella (BRD 847) expressing fragment C of tetanus toxoid, since little information is available to explain how these vectors induce mucosal IgA responses. A single dose of BRD 847 elicited serum IgG2a and mucosal IgA anti-tetanus toxoid Ab responses. To assess Th1-and Th2-type responses, CD4+ T cells from Peyer's patches and spleen were restimulated in vitro, and cytokine-specific ELISPOT, ELISA, and reverse transcriptase-PCR assays were used to assess cytokine patterns. CD4+ T cells produced IFN-gamma and IL-2 as well as IL-10, but not IL-4 or IL-5. Although IL-6 was elevated, further purification of cells from in vitro cultures into CD4+ Mac-1- T cells and Mac-1+ CD4- cells revealed that only the latter cell population had consistently elevated IL-6 gene expression, whereas both sorted populations exhibited increased IFN-gamma and IL-10 gene expression. Thus, orally administered recombinant Salmonella expressing fragment C of tetanus toxoid elicited dominant Ag-specific Th1-type responses together with Th2-type cells producing IL-10 in both mucosal and systemic tissues. Macrophages producing IL-6 were also evident. Our results are consistent with the suggestion that Ag-specific Th1 cells and their derived cytokines, IFN-gamma and IL-2, and Th2-derived IL-10 together with IL-6 produced by macrophages provide important signals for the development of mucosal IgA and serum IgG subclass responses in the absence of preferential expression of Th2 cytokines IL-4 and IL-5.
A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding (2009)

This work describes the rational design, synthesis, and study of a ligand that selectively complexes CUG repeats in RNA (and CTG repeats in DNA) with high nanomolar affinity. This sequence is considered a causative agent of myotonic dystrophy type 1 (DM1) because of its ability to sequester muscleblind-like (MBNL) proteins. Ligand 1 was synthesized in two steps from commercially available compounds, and its binding to CTG and CUG repeats in oligonucleotides studied. Isothermal titration calorimetry studies of 1 with various sequences showed a preference toward the T-T mismatch (K(d) of 390 +/- 80 nM) with a 13-, 169-, and 85-fold reduction in affinity toward single C-C, A-A, and G-G mismatches, respectively. Binding and Job analysis of 1 to multiple CTG step sequences revealed high affinity binding to every other T-T mismatch with negative cooperativity for proximal T-T mismatches. The affinity of 1 for a (CUG)(4) step provided a K(d) of 430 nM with a binding stoichiometry of 1:1. The preference for the U-U in RNA was maintained with a 6-, >143-, and >143-fold reduction in affinity toward single C-C, A-A, and G-G mismatches, respectively. Ligand 1 destabilized the complexes formed between MBNL1N and (CUG)(4) and (CUG)(12) with IC(50) values of 52 +/- 20 microM and 46 +/- 7 microM, respectively, and K(i) values of 6 +/- 2 microM and 7 +/- 1 microM, respectively. These values were only minimally altered by the addition of competitor tRNA. Ligand 1 does not destabilize the unrelated RNA-protein complexes the U1A-SL2 RNA complex and the Sex lethal-tra RNA complex. Thus, ligand 1 selectively destabilizes the MBNL1N-poly(CUG) complex.
Laccase-Catalyzed Oxidation of Mn 2+ in the Presence of Natural Mn 3+ Chelators as a Novel Source of Extracellular H 2 O 2 Production and Its Impact on Manganese Peroxidase (2002)

A purified and electrophoretically homogeneous blue laccase from the litter-decaying basidiomycete Stropharia rugosoannulata with a molecular mass of approximately 66 kDa oxidized Mn(2+) to Mn(3+), as assessed in the presence of the Mn chelators oxalate, malonate, and pyrophosphate. At rate-saturating concentrations (100 mM) of these chelators and at pH 5.0, Mn(3+) complexes were produced at 0.15, 0.05, and 0.10 micromol/min/mg of protein, respectively. Concomitantly, application of oxalate and malonate, but not pyrophosphate, led to H(2)O(2) formation and tetranitromethane (TNM) reduction indicative for the presence of superoxide anion radical. Employing oxalate, H(2)O(2) production, and TNM reduction significantly exceeded those found for malonate. Evidence is provided that, in the presence of oxalate or malonate, laccase reactions involve enzyme-catalyzed Mn(2+) oxidation and abiotic decomposition of these organic chelators by the resulting Mn(3+), which leads to formation of superoxide and its subsequent reduction to H(2)O(2). A partially purified manganese peroxidase (MnP) from the same organism did not produce Mn(3+) complexes in assays containing 1 mM Mn(2+) and 100 mM oxalate or malonate, but omitting an additional H(2)O(2) source. However, addition of laccase initiated MnP reactions. The results are in support of a physiological role of laccase-catalyzed Mn(2+) oxidation in providing H(2)O(2) for extracellular oxidation reactions and demonstrate a novel type of laccase-MnP cooperation relevant to biodegradation of lignin and xenobiotics.
Determination of seed oil content and fatty acid composition in sunflower through the analysis of intact seeds, husked seeds, meal and oil by near‐infrared reflectance spectroscopy (1998)

Abstract A methodological study was conducted to test the potential of near‐infrared reflectance spectroscopy (NIRS) to estimate the oil content and fatty acid composition of sunflower seeds. A set of 387 intact‐seed samples, each from a single plant, were scanned by NIRS, and 120 of them were selected and further scanned as husked seed, meal, and oil. All samples were analyzed for oil content (nuclear magnetic resonance) and fatty acid composition (gas chromatography), and calibration equations for oil content and individual fatty acids (C 16:0 , C 16:1 , C 18:0 , C 18:1 , and C 18:2 ) were developed for intact seed, husked seed, meal, and oil. For intact seed, the performance of the calibration equations was evaluated through both cross‐ and external validation, while cross‐validation was used in the rest. The results showed that NIRS is a reliable and accurate technique to estimate these traits in sunflower oil (validation r 2 ranged from 0.97 to 0.99), meal ( r 2 from 0.92 to 0.98), and husked seeds ( r 2 from 0.90 to 0.97). According to these results, there is no need to grind the seeds to scan the meal; similarly accurate results are obtained by analyzing husked seeds. The analysis of intact seeds was less accurate ( r 2 from 0.76 to 0.85), although it is reliable enough to use for pre‐screening purposes to identify variants with significantly different fatty acid compositions from standard phenotypes. Screening of intact sunflower seeds by NIRS represents a rapid, simple, and cost‐effective alternative that may be of great utility for users who need to analyze a large number of samples.
Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells. (1981)

The cytotoxicities of a number of antineoplastic agents to oxygenated and hypoxic EMT6 mouse mammary tumor cells in culture were examined. Based on the relative sensitivities of cells under aerobic and hypoxic conditions, drugs were placed into three categories. Drugs that were preferentially toxic to cells under oxygenated conditions were classified as type 1 agents; this group includes bleomycin, procarbazine, streptonigrin, actinomycin D, and vincristine. Type 2 agents were those preferentially toxic to cells under hypoxic conditions. These include mitomycin C and Adriamycin. On the basis of other published reports, the glucose analogs, 5-thio-D-glucose and 2-deoxy-D-glucose, and the radiosensitizers, misonidazole and metronidazole, can also be placed in this category. Several antineoplastic agents showed no major preferential toxicity to cells under the conditions of oxygenation or hypoxia used in these experiments and were placed in a third class. This group (type 3) includes 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, cis-diamminedichloroplatinum(II), 5-fluorouracil, and methotrexate. The success of many combination chemotherapy and combined modality treatments may be due to their ability to kill both the hypoxic and aerobic cell populations of solid tumors. Future chemotherapeutic regimens for the treatment of solid tumors should include agents and modalities directed toward the hypoxic cell population of the tumor, as well as toward the proliferating and nonproliferating tumor cell compartments; a therapeutic approach to the selection of antineoplastic agents for use in combination based upon physiological considerations of the architecture of solid tumors is presented.
An SC35-like Protein and a Novel Serine/Arginine-rich Protein Interact with Arabidopsis U1-70K Protein (1999)

The U1 small nuclear ribonucleoprotein 70-kDa protein, a U1 small nuclear ribonucleoprotein-specific protein, has been shown to have multiple roles in nuclear precursor mRNA processing in animals. By using the C-terminal arginine-rich region of Arabidopsis U1-70K protein in the yeast two-hybrid system, we have identified an SC35-like (SR33) and a novel plant serine/arginine-rich (SR) protein (SR45) that interact with the plant U1-70K. The SR33 and SR45 proteins share several features with SR proteins including modular domains typical of splicing factors in the SR family of proteins. However, both plant SR proteins are rich in proline, and SR45, unlike most animal SR proteins, has two distinct arginine/serine-rich domains separated by an RNA recognition motif. By using coprecipitation assays we confirmed the interaction of plant U1-70K with SR33 and SR45 proteins. Furthermore, in vivo and in vitro protein-protein interaction experiments have shown that SR33 protein interacts with itself and with SR45 protein but not with two other members (SRZ21 and SRZ22) of the SR family that are known to interact with the Arabidopsis full-length U-70K only. A Clk/Sty protein kinase (AFC-2) from Arabidopsis phosphorylated four SR proteins (SR33, SR45, SRZ21, and SRZ22). Coprecipitation studies have confirmed the interaction of SR proteins with AFC2 kinase, and the interaction between AFC2 and SR33 is modulated by the phosphorylation status of these proteins. These and our previous results suggest that the plant U1-70K interacts with at least four distinct members of the SR family including SR45 with its two arginine/serine-rich domains, and the interaction between the SR proteins and AFC2 is modulated by phosphorylation. The interaction of plant U1-70K with a novel set of proteins suggests the early stages of spliceosome assembly, and intron recognition in plants is likely to be different from animals.
Identification of the Minimal Replicon of Lactococcus lactis subsp. lactis UC317 Plasmid pCI305 (1990)

Replication functions of the stable, cryptic 8.7-kilobase (kb) plasmid pCI305 from multi-plasmid-containing Lactococcus lactis subsp. lactis UC317 were studied. Analysis of this replicon was facilitated by the construction of replication probe vectors that consisted of the pBR322 replication region, a pUC18-derived multiple cloning site, and either the cat gene of pC194 (pCI341; 3.1 kb) or the erm gene of pAMbeta1 (pCI3330; 4.0 kb). Plasmid pCI305 was introduced into plasmid-free L. lactis subsp. lactis MG1363Sm, a streptomycin-resistant derivative of MG1363, by a transformation procedure with the 75-kb lactose-proteinase plasmid pCI301 of UC317 as a marker plasmid. A combination of transposon Tn5 mutagenesis and subcloning in pCI341 and pCI3330 with individual Tn5 insertions around the replication region facilitated the identification of a 1.6-kb minimal replicon on pCI305. This region was separable into two domains: (i) a 1.3-kb region (repB) encoding a trans-acting function (in vitro transcription-translation studies suggested the involvement of a 48-kilodalton protein); and (ii) a 0.3-kb region (repA) sufficient to direct replication when provided with repB in trans and thus probably containing the origin of replication. Lactococcus-Escherichia coli shuttle vectors based on the pCI305 replication region were constructed.
Inhibition of Extratesticular Stimuli to Prostatic Growth in the Castrate Rat by Antiandrogens (1970)

In the immature castrate rat, the antiandrogens cyproterone (C) (30 or 150 mg⁄ kg) and cyproterone acetate (CA) (10 or 50 mg⁄kg) inhibited the growth of the ventral prostate and seminal vesicles that was induced by dehydroepiandrosterone (DHA), androstenedione (A), or testosterone (T) injected at various doses for 7 days. When the lowest doses of androgen were used (DHA 0.4 mg, A 0.02 mg, and T 0.015 mg), C and CA were often able to maintain the weights of target organs at castrate levels. CA was about 3 times more potent than C in antiandrogenic activity. CA also significantly inhibited the increase in prostatic weight that occurred after 14 days of administration of ACTH (20 U⁄day), prolactin (1 mg⁄day) plus ACTH (5 mg⁄day), or prolactin (1 mg⁄day) plus DHA (0.2 mg⁄day). It is concluded that C and CA can inhibit the known extratesticular stimuli to prostatic growth in the rat. These stimuli may all be mediated by an androgendependent cellular response. (Endocrinology87: 624, 1970)
Observation of High‐Aspect‐Ratio Nanostructures Using Capillary Lithography (2005)

Several intriguing nanostructures, such as mushroom-like nanopillars, vertical nanopillars (see Figure), and nanospheres, are made using capillary lithography and a new, UV-curable mold consisting of polyurethane functionalized with an acrylate group. An aspect ratio as high as five is achieved for nanopillars 90 nm in diameter.
Differential Effects of Endogenous and Exogenous Interferon-γ on Immunoglobulin E, Cellular Infiltration, and Airway Responsiveness in a Murine Model of Allergic Asthma (1998)

The inflammatory response as seen in human allergic asthma is thought to be regulated by Th2 cells. It has been shown that interferon-gamma (IFN-gamma) can downregulate the proliferation of Th2 cells and therefore might be of therapeutic use. In the present study we have investigated the in vivo role of endogenous and exogenous IFN-gamma in a murine model with features reminiscent of human allergic asthma. IFN-gamma gene knockout (GKO) and wild-type mice were sensitized with ovalbumin and exposed to repeated ovalbumin aerosol challenges. In addition, wild-type mice were treated with intraperitoneal or nebulized recombinant murine IFN-gamma during the challenge period. Sensitized wild-type mice exhibited upregulated ovalbumin-specific IgE in serum, and airway hyperresponsiveness and infiltration of eosinophils and mononuclear cells in the bronchoalveolar lavage fluid (BALF) after ovalbumin challenge. In contrast, in GKO mice only reduced eosinophilic infiltration in the BALF was observed after ovalbumin challenge. In wild-type mice, parenteral IFN-gamma treatment downregulated ovalbumin-specific IgE levels in serum, and airway hyperresponsiveness and cellular infiltration in the BALF, whereas aerosolized IFN-gamma treatment only suppressed airway hyperresponsiveness. In vitro experiments showed that these effects of IFN-gamma appear not to be mediated via a direct effect on the cytokine production of antigen-specific Th2 cells. These data indicate that airway hyperresponsiveness can be downregulated by IFN-gamma locally in the airways, whereas for downregulation of IgE and cellular infiltration systemic IFN-gamma is needed. The present study shows that exogenous IFN-gamma can downregulate the allergic response via an antigen-specific T-cell independent mechanism, but at the same time endogenous IFN-gamma plays a role in an optimal response.
Stress-controlled x-ray mask absorber using pulse-current gold plating (1992)

The application of pulse-current gold plating has been studied in the fabrication of x-ray mask patterns to attain uniform thickness and low stress. Pulse-current plating with low average current density (iav) has proven effective in improving uniform plating thickness over a wide range of pattern sizes. This result can be explained through the duplex-diffusion layer model. Stress in the gold plated by low iav becomes compressive. However, this stress can be eliminated by annealing. This annealing effect is attributable to the contraction in volume of plated gold due to the thermal desorption of hydrogen atoms.
Reports on contrast media reactions: analysis of data from reports to the U.S. Food and Drug Administration. (1997)

All of these factors merit consideration in the evaluation of the utility of a given contrast medium.
Expressed human immunoglobulin ϰ genes and their hypermutation (1993)

The question of which germ-line V kappa genes are expressed was studied by sequencing 70 different cDNA clones from a human spleen library and one clone from a fetal liver library. The sequences were compared to a data base containing all germ-line V kappa gene and pseudogene sequences. In addition, 51 rearranged genomic V kappa genes, 170 cDNA and 74 kappa proteins from the literature were assigned to specific germ-line V kappa genes and included in the comparisons. Not all the known, potentially functional V kappa genes were found to be expressed, while some genes with minor defects are. The total number of expressed genes is smaller than expected: so far 21 germ-line genes and 5 pairs of duplicated identical genes are known to be transcribed. The corresponding numbers for rearranged genomic V kappa genes and kappa proteins are 17 plus 4 and 7 plus 7, respectively. A second aim of the study was to find out whether the expressed repertoire contains derivatives of germ-line V kappa genes still missing in our data base; no evidence for the existence of such genes was found. Several cDNA clones contained additional nucleotides between the V kappa and J kappa gene segments, which may be germ-line derived, inserted by terminal deoxynucleotidyl transferase or introduced by other mechanisms. Somatic gene conversion seems not to play a major role in creating the human kappa gene diversity. Various aspects of the hypermutation of kappa genes are discussed and the formation of block mutations, i.e. the alterations of two or more adjacent nucleotides is stressed as a remarkable feature of the process.
The effects and effectiveness of gamma-hydroxybutyrate in patients with narcolepsy. (1985)

Thirty patients with polysomnographically confirmed narcolepsy were treated with GHB (gamma-hydroxybutyrate) for up to 30 weeks. The number of nightly awakenings significantly decreased, while Stages 3 and 4 sleep substantially increased. The clinical symptoms of cataplexy, sleep paralysis, hypnogogic hallucinations, daily naps, and sleep attacks all showed significant improvements. Daytime sleepiness, while not completely eliminated, was controlled with lower doses of stimulant medication than patients were taking before the study. No patient developed tolerance to the drug, and no serious side effects were noted.
Role of endotoxemia in cardiovascular dysfunction and mortality. Escherichia coli and Staphylococcus aureus challenges in a canine model of human septic shock. (1989)

Using different types of bacteria and a canine model simulating human septic shock, we investigated the role of endotoxin in cardiovascular dysfunction and mortality. Either Escherichia coli (a microorganism with endotoxin) or Staphylococcus aureus (a microorganism without endotoxin) were placed in an intraperitoneal clot in doses of viable or formalin-killed bacteria. Cardiovascular function of conscious animals was studied using simultaneous radionuclide heart scans and thermodilution cardiac outputs. Serial plasma endotoxin levels were measured. S. aureus produced a pattern of reversible cardiovascular dysfunction over 7-10 d that was concordant (P less than 0.01) with that of E. coli. Although this cardiovascular pattern was not altered by formalin killing (S. aureus and E. coli), formalin-killed organisms produced a lower mortality and less myocardial depression (P less than 0.01). S. aureus, compared to E. coli, produced higher postmortem concentrations of microorganisms and higher mortality (P less than 0.025). E. coli produced significant endotoxemia (P less than 0.01), though viable organisms (versus nonviable) resulted in higher endotoxin blood concentrations (P less than 0.05). Significant endotoxemia did not occur with S. aureus. Thus, in the absence of endotoxemia, S. aureus induced the same cardiovascular abnormalities of septic shock as E. coli. These findings indicate that structurally and functionally distinct microorganisms, with or without endotoxin, can activate a common pathway resulting in similar cardiovascular injury and mortality.
Topical sodium cromoglycate in the management of atopic eczema—a controlled trial (1985)

A double-blind, group comparison trial of a topical cream containing 4% sodium cromoglycate (SCG) was undertaken in forty-six patients with chronic atopic eczema. A statistically significant improvement was seen after 9 weeks in the actively treated patients compared with the placebo group. However, in general, no benefit was observed in severe eczema, perhaps due in some part to the seemingly late onset of action of SCG. Measurement of total serum IgE before and after the trial showed an increase in levels which was apparently unrelated to treatment with SCG or placebo or to a change in severity of the eczema. The amount of SCG in the urine was small and very variable, indicating low percutaneous absorption. The calculated bioavailability ranged from 0.01% to 2.75% of the applied dose. These results together with follow-up studies suggest that topical SCG as a long-term measure may be useful in the management of mild or moderately severe eczema, reducing the frequency of acute exacerbations.
Optical equalization of fiber chromatic dispersion in a 5-Gb/s transmission system (1990)

A 5-Gb/s lightwave transmission experiment demonstrates the effectiveness of an all-pass-type fiber Fabry-Perot optical equalizer for eliminating an error floor caused by laser chirp and chromatic dispersion.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
MiS-MALDI: microgel-selected detection ofproteinbiomarkers by MALDI-ToFmass spectrometry (2010)

Intensified efforts to decipher the origin of disease at the molecular level stimulate the emergence of more efficient proteomic technologies. To complement this, attempts are being made to identify new predictive biomarkers for building more reliable biomarker patterns. As biomarker research gathers pace an immediate interest becomes focused on platforms, which although based on mainstream approaches, are more amenable to specialist tasks. Particularly relevant this is for disease-specific biomarkers, which are present at very low concentrations in multicomponent biological fluids and require depletion protocols enabling their separation from high-abundance components. In this report, we describe a new strategy allowing the rapid detection of target protein biomarkers by MALDI-ToF mass spectrometry. The approach relies on selective sequestering of target proteins from complex media by engineered microgels, which select proteins by their size (<30 kDa) and isoelectric points (protein pI <6.5). Subsequently, biomarker-loaded microgels are subjected to direct mass-spectrometric analysis without the need for preceding protein extraction. Exemplified by a natural protein-folding motif, coiled-coil, the monitoring of hierarchical folding-dependent macromolecular systems by the approach is also shown. The described strategy offers a general rationale for versatile platforms for high throughput proteomics and holds promise for proteome fingerprinting of biomolecular interactions.