gebhart/patrepeval huggingface dataset:
Microbial Metabolic Networks at the Mucus Layer Lead to Diet-Independent Butyrate and Vitamin B 12 Production by Intestinal Symbionts (2017)

<i>Akkermansia muciniphila</i> has evolved to specialize in the degradation and utilization of host mucus, which it may use as the sole source of carbon and nitrogen. Mucus degradation and fermentation by <i>A. muciniphila</i> are known to result in the liberation of oligosaccharides and subsequent production of acetate, which becomes directly available to microorganisms in the vicinity of the intestinal mucosa. Coculturing experiments of <i>A</i><i>muciniphila</i> with non-mucus-degrading butyrate-producing bacteria <i>Anaerostipes caccae</i>, <i>Eubacterium hallii</i>, and <i>Faecalibacterium prausnitzii</i> resulted in syntrophic growth and production of butyrate. In addition, we demonstrate that the production of pseudovitamin B<sub>12</sub> by <i>E. hallii</i> results in production of propionate by <i>A. muciniphila</i>, which suggests that this syntrophy is indeed bidirectional. These data are proof of concept for syntrophic and other symbiotic microbe-microbe interactions at the intestinal mucosal interface. The observed metabolic interactions between <i>A</i><i>muciniphila</i> and butyrogenic bacterial taxa support the existence of colonic vitamin and butyrate production pathways that are dependent on host glycan production and independent of dietary carbohydrates. We infer that the intestinal symbiont <i>A. muciniphila</i> can indirectly stimulate intestinal butyrate levels in the vicinity of the intestinal epithelial cells with potential health benefits to the host.<b>IMPORTANCE</b> The intestinal microbiota is said to be a stable ecosystem where many networks between microorganisms are formed. Here we present a proof of principle study of microbial interaction at the intestinal mucus layer. We show that indigestible oligosaccharide chains within mucus become available for a broad range of intestinal microbes after degradation and liberation of sugars by the species <i>Akkermansia muciniphila</i> This leads to the microbial synthesis of vitamin B<sub>12</sub>, 1,2-propanediol, propionate, and butyrate, which are beneficial to the microbial ecosystem and host epithelial cells.
A bovine papillomavirus type 1-encoded modulator function is dispensable for transient viral replication but is required for establishment of the stable plasmid state (1986)

A bovine papillomavirus (BPV) type 1-encoded function (M) which is a negative regulator of viral plasmid replication has been described elsewhere (Berg et al. Cell, in press; Roberts and Weintraub, Cell, in press). We report here that expression of M, which is a repressor of transient BPV replication and is not required as a positive factor in these assays, is required for the establishment of the viral genome as a stable nuclear plasmid. This function is encoded in part by the 5' portion of the BPV E1 open reading frame, whereas the 3' part of this open reading frame encodes a positive replication function (R). The R function is required for early replication events. We used transient replication assays to define the phenotypes of mutants in both the R and M genes and complementation tests to show that R and M define two separate genes. We showed that R- and M- mutants could also complement each other in stable assays. In cotransfection experiments, M- mutants had a lethal effect on the growth of G418-resistant colonies, and in addition their morphological transformation efficiencies were reduced. The rare colonies which did appear contained the mutant DNA integrated into the cellular genome. R- mutants transformed with wild-type efficiency, and the mutant DNA was also found integrated. When cotransfected, R- and M- mutants could each be established as unrearranged plasmids.
Characterization of cancer stroma markers: in silico analysis of an mRNA expression database for fibroblast activation protein and endosialin. (2005)

Standardized, high-throughput RNA detection with microarray chips allows for the construction of genome-wide databases for tissue specimens suitable for in silico electronic Northern blot (eNorthern) analysis of marker genes. We used the BioExpress database, which contains transcriptional profiles of normal and cancer samples, to examine two putative markers of cancer stroma: fibroblast activation protein-alpha (FAP-alpha) and endosialin. Analyses for FAP-alpha showed that normal tissues generally lack RNA signals, with the exception of endometrium. Typing of tumors revealed prominent FAP-alpha signals in cancer types marked by desmoplasia, and localization of FAP-alpha in reactive cancer stroma was confirmed by immunohistochemistry. A subset of sarcomas displayed prominent FAP-alpha signals localizing to the malignant cells. For endosialin, eNorthern analyses showed low to moderate RNA signals in many normal organs, whereas immunohistochemistry revealed endosialin in only some tissues, such as endometrium. Endosialin was detected at the RNA and protein level in sarcomas, notably malignant fibrous histiocytomas. Low to moderate endosialin RNA signals were found in epithelial cancer types for which immunostaining identifies expression in subsets of tumor capillaries or fibroblasts. These findings extend the FAP-alpha and endosialin profiling in silico to an unbiased tumor database and place both molecules in a novel context of endometrial biology and sarcoma subtyping. Our findings suggest that BioExpress can be searched directly for tumor stroma markers but may need prior enrichment for markers with narrow cellular representation, such as endosialin. Constructing databases from microdissected cancer tissues may be an essential step for tumor stroma-targeted therapies.
polyhomeotic regulatory sequences induce developmental regulator-dependent variegation and targeted P-element insertions in Drosophila. (1993)

Variegation of the miniwhite gene is observed in a euchromatic context in transformant lines that contain a P transposon including regulatory sequences of the polyhomeotic (ph) gene upstream of the resident miniwhite gene (P[ph]). This variegated phenotype is not affected by most of the genetic modifiers of heterochromatic position-effect variegation (PEV) nor by removal of the Y chromosome. Interestingly, it is sensitive to ph and Polycomb (Pc) mutations, which are known to affect homeotic gene regulation. Regulatory DNA of ph can also mediate transvection of the miniwhite gene. This transvection is abolished in a ph but not in a zeste mutant background. In addition, P[ph] inserts preferentially in sites corresponding to PH/PC protein-binding sites as defined at the polytene chromosome level. These insertions induce an unusually high proportion of mutations in genes affecting homeotic gene regulation. In particular, one insertion is located within the tramtrack locus, which is thought to regulate fushi tarazu, an Ultrabithorax activator. We suggest that a multimeric complex containing PH and PC proteins, at a minimum, causes a local and clonally inherited heterochromatinization, which maintains the repressed state of transcription of the homeotic genes.
Analysis of an immunodominant region of infectious bronchitis virus. (1989)

We analyzed the antigenic fine-structure of an immunodominant region in the peplomer protein of infectious bronchitis virus. This region near the N-terminus of the S2 subunit is recognized by polyclonal antisera and by the majority of mAb that cross-react with denatured protein. Despite their involvement in neutralization, epitopes in this region were conserved in different serotypes. Epitopes of four mAb and two chicken antisera were localized by using prokaryotic expression of cDNA fragments, and overlapping peptides with lengths increasing from 3 to 12 residues (PEPSCAN). We found overlapping epitopes with lengths of 6, 9, 11, and more than 17 residues. The results indicate that the expression products are antigenically equivalent to denatured protein fragments. This suggests a general strategy for the localization of sequential epitopes in large proteins. We propose that the immunodominance of the N-terminal region of S2 is explained by features of the protein structure. Presumably, this region is a protruding protein segment of about 20 residues with a high local mobility, as indicated by the antigenicity of the peptides. The conservation of the sequence points to an involvement in a molecular recognition process during infection.
HTS-Corrector: software for the statistical analysis and correction of experimental high-throughput screening data (2006)

This paper describes HTS-Corrector, a software application for the analysis of HTS data, detection and visualization of systematic error, and corresponding correction of HTS signals. Three new methods for the statistical analysis and correction of raw HTS data are included in HTS-Corrector: background evaluation, well correction and hit-sigma distribution procedures intended to minimize the impact of systematic errors. We discuss the main features of HTS-Corrector and demonstrate the benefits of the algorithms.
Emotion, olfaction, and the human amygdala: Amygdala activation during aversive olfactory stimulation (1997)

Electrophysiologic and lesion studies of animals increasingly implicate the amygdala in aspects of emotional processing. Yet, the functions of the human amygdala remain poorly understood. To examine the contributions of the amygdala and other limbic and paralimbic regions to emotional processing, we exposed healthy subjects to aversive olfactory stimuli while measuring regional cerebral blood flow (rCBF) with positron emission tomography. Exposure to a highly aversive odorant produced strong rCBF increases in both amygdalae and in the left orbitofrontal cortex. Exposure to less aversive odorants produced rCBF increases in the orbitofrontal cortex but not in the amygdala. Change of rCBF within the left amygdala and the left OFC was highly intercorrelated, indicating a strong functional interaction between these brain regions. Furthermore, the activity within the left amygdala was associated significantly with subjective ratings of perceived aversiveness. These findings provide evidence that the human amygdala participates in the hedonic or emotional processing of olfactory stimuli.
Differential Activation of Peroxisome Proliferator-activated Receptors by Eicosanoids (1995)

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that regulate gene transcription in response to peroxisome proliferators and fatty acids. PPARs also play an important role in the regulation of adipocyte differentiation. It is unclear, however, what naturally occurring compounds activate each of the PPAR subtypes. To address this issue, a screening assay was established using heterologous fusions of the bacterial tetracycline repressor to several members of the peroxisome proliferator-activated receptor (PPAR) family. This assay was employed to compare the activation of PPAR family members by known PPAR activators including peroxisome proliferators and fatty acids. Interestingly, the activation of PPARs by fatty acids was partially inhibited by the cyclooxygenase inhibitor indomethacin, which prevents prostaglandin synthesis. Indeed, prostaglandins PGA1 and 2, PGD1 and 2, and PGJ2-activated PPARs, while a number of other prostaglandins had no effect. We also screened a variety of hydroxyeicosatetraenoic acids (HETEs) for the ability to activate PPARs. 8(S)-HETE, but not other (S)-HETEs, was a strong activator of PPAR alpha. Remarkably, PPAR activation by 8(S)-HETE was stereoselective. In addition, 8(S)-HETE was able to induce differentiation of 3T3-L1 preadipocytes. These results indicate that PPARs are differentially activated by naturally occurring eicosanoids and related molecules.
EDIBLE FILMS AND COATINGS: A REVIEW (1986)

A technical overview discussed the rationale for using edible films for preventing moisture loss from films while allowing permeability of oxygen and carbon dioxide to prevent anaerobic bacterial growth within the encased food. Detailed attention also is given to the characteristics of the types of edible films, covering specific polysaccharide, protein, and lipid films or blends of these. Moisture-, gas-, and solute-barrier properties are discussed, as well as the use of film additives. Further research needs are identified.(wz)
Transformations of steroidal neopentyl systems. Part IV. Stereochemistry of products of reaction of methyl-lithium with Δ5-19-aldehydes (1968)

The reaction of methyl-lithium with 3β,17β-diacetoxyandrost-5-en-19-al and certain transformations of the derived products have been studied. Only the 19R-alcohol was formed by this reaction and its stereochemistry was proved through transformation into 17β-acetoxy-3α-methoxy-19-methyl-5α-androstane 3,19-oxide (9d). A reduction–oxidation reaction involving a 1,5-hydride ion transfer was observed during ethylene dioxide formation.
Complementary Effects of Interleukin-15 and Alpha Interferon Induce Immunity in Hepatitis B Virus Transgenic Mice (2016)

With 350 million people affected worldwide and 600,000 annual deaths due to HBV-induced liver cirrhosis and/or hepatocellular carcinoma, chronic hepatitis B (CHB) is a major health problem. However, current treatment options are costly and not very effective and/or need to be administered for life. The unprecedented efficacy of the strategy described in our paper may offer an alternative and is relevant for a broad spectrum of readers because of its clear translational importance to other chronic viral infections in which a hyporesponsive antigen-specific T cell repertoire prevents clearance of the pathogen.
Non-conventional liquid crystals—the importance of micro-segregation for self-organisation (1998)

Selected examples of recently synthesised non-conventional liquid crystals are highlighted. These are cyclic and open chain oligoamides, molecules containing tetrahedral or octahedral central cores, dendrimers, polyhydroxy amphiphiles, taper shaped molecules, liquid crystals with perfluorinated or oligosiloxane segments, rod-coil molecules as well as special types of polycatenar and laterally branched calamitic molecules. Their mesomorphic properties are discussed as a consequence of incompatibility, micro-segregation and space filling. The analysis is based on the general concept of amphiphilicity, which describes any chemical or structural contrast within a molecule, such as hydrophilic/lipophilic, polar/non-polar, hydrocarbon/fluorocarbon, oligosiloxane/hydrocarbon or rigid/flexible. These non-conventional liquid crystals will be regarded as block molecules. Depending on the degree of chemical and structural difference and the size of the different building blocks micro-segregation can occur with formation of lamellar, columnar or spheroidal aggregates which organise to smectic, columnar and cubic mesophases. The striking analogies between the polymorphism of thermotropic and lyotropic liquid crystals and block-copolymers are pointed out.
Monoclonal antibody disulfide reduction during manufacturing (2013)

Manufacturing-induced disulfide reduction has recently been reported for monoclonal human immunoglobulin gamma (IgG) antibodies, a widely used modality in the biopharmaceutical industry. This effect has been tied to components of the intracellular thioredoxin reduction system that are released upon cell breakage. Here, we describe the effect of process parameters and intrinsic molecule properties on the extent of reduction. Material taken from cell cultures at the end of production displayed large variations in the extent of antibody reduction between different products, including no reduction, when subjected to the same reduction-promoting harvest conditions. Additionally, in a reconstituted model in which process variables could be isolated from product properties, we found that antibody reduction was dependent on the cell line (clone) and cell culture process. A bench-scale model using a thioredoxin/thioredoxin reductase regeneration system revealed that reduction susceptibility depended on not only antibody class but also light chain type; the model further demonstrates that the trend in reducibility was identical to DTT reduction sensitivity following the order IgG1λ > IgG1κ > IgG2λ > IgG2κ. Thus, both product attributes and process parameters contribute to the extent of antibody reduction during production.
Disk scheduling with quality of service guarantees (2003)

The paper introduces YFQ, a new disk scheduling algorithm that allows applications to set aside for exclusive use portions of the disk bandwidth. We implemented YFQ as part of the Eclipse/BSD operating system, which is derived from FreeBSD, a version of 4.4 BSD Unix. YFQ's disk bandwidth reservations can guarantee file accesses with high throughput, low delay, and good fairness. Such quality of service (QoS) guarantees to individual applications unfortunately can also hinder global disk scheduling optimizations. We propose and evaluate several disk scheduling enhancements that promote global optimizations and give to YFQ aggregate disk throughput approaching that of FreeBSD's conventional disk scheduler, which does not provide QoS guarantees. We believe that our enhancements may be helpful also in other disk scheduling algorithms.
Techniques for investigating substrate metabolism in patients. (1981)

Studies of dynamic aspects of substrate metabolism in patients can be made with a variety of techniques. Methods include indirect calorimetry, substrate load tests, measurement of arteriovenous differences with use of the Fick principle, and isotope infusions. Recent developments in stable isotope methodology have made available safe techniques for accurate measurement of the turnover of plasma substrates in patients. The use of deuterated, 13C, and 15N isotopes enables the turnover of several substrates to be measured at the same time. It is hoped that the primed constant infusion of stable isotopes combined with indirect calorimetry will lead to a greater understanding of metabolism in ill patients.
Object oriented design with applications (1990)

Booch gives practical guidance for the construction of complex object-oriented design methods. A pioneer in the area, he draws on his extensive experience in developing very large software systems to illuminate both the complex challenges and potential problems developers often face.
PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells (2016)

Glioblastoma is the most aggressive primary brain tumor and responds poorly to currently available therapies. Transcriptomic characterization of glioblastoma has identified distinct molecular subtypes of glioblastoma. Gain-of-function alterations leading to enhanced platelet-derived growth factor (PDGF) signaling are commonly observed in the proneural subtype of glioblastoma and can drive gliomagenesis. However, little is known about the downstream effectors of PDGF signaling in glioblastoma. Using a mouse model of proneural glioma and comparative transcriptomics, we determined that PDGF signaling upregulated ubiquitin-specific peptidase 1 (Usp1) to promote the survival of murine proneural glioma cells. Mechanistically, we found that PDGF signaling regulated the expression of the E2F transcription factors, which directly bound to and activated Usp1 Furthermore, PDGF-mediated expression of USP1 led to the stabilization of Inhibitor of DNA-binding 2 (ID2), which we found to be required for glioma cell survival. Genetic ablation of Id2 delayed tumor-induced mortality, and pharmacologic inhibition of USP1, resulting in decreased ID2 levels, also delayed tumorigenesis in mice. Notably, decreased USP1 expression was associated with prolonged survival in patients with proneural glioblastoma, but not with other subtypes of glioblastoma. Collectively, our findings describe a signaling cascade downstream of PDGF that sustains proneural glioblastoma cells and suggest that inhibition of the PDGF-E2F-USP1-ID2 axis could serve as a therapeutic strategy for proneural glioblastoma featuring increased PDGF signaling. Cancer Res; 76(10); 2964-76. ©2016 AACR.
Meniscal material properties are minimally affected by matrix stabilization using glutaraldehyde and glycation with ribose (2004)

Knee meniscus replacement holds promise, but current allografts are susceptible to biodegradation. Matrix stabilization with glutaraldehyde, a crosslinking agent used clinically to fabricate cardiovascular bioprostheses, or with glycation, a process of crosslinking collagen with sugars such as ribose, is a potential means of rendering tissue resistant to such degradation. However, stabilization should not significantly alter meniscal material properties, which could disturb normal function in the knee. Our objective was to evaluate the effects of glutaraldehyde- and glycation-induced matrix stabilization on the material properties of porcine meniscus. Normal untreated meniscus specimens were tested in confined compression at one of three applied stresses (0.069, 0.208, 0.347 MPa), subjected to either a glutaraldehyde or glycation stabilization treatment, and then re-tested to measure changes in tissue aggregate modulus, permeability, and compressive strain at equilibrium. Changes in these properties significantly increased with glutaraldehyde concentration and exposure time to ribose. One glutaraldehyde and three glycation treatments did not alter aggregate modulus or compressive strain at equilibrium compared to controls (p > 0.10). However, all treatments increased permeability by at least 108% compared to controls (p < 0.001). This study reveals a dose-dependent relationship between meniscal material properties and certain stabilization conditions and identifies treatments that minimally affect these properties. Further research is necessary to determine whether these treatments prevent enzymatic degradation before and after surgical implantation in the knee.
A population‐based case‐control study of EBV and other viral antibodies among persons with Hodgkin's disease and their siblings (1984)

The Epstein-Barr virus (EBV) has been consistently found to be associated with Hodgkin's disease (HD) in two ways: cases generally have elevated titer distributions of antibodies against the viral capsid antigen, and the occurrence of HD among persons with a history of EBV infectious mononucleosis is two or three times higher than expected. We evaluated this association by measuring the prevalence and level of antibodies against EBV and related viruses among 304 cases of HD interviewed in a population-based study in comparison to 285 of their siblings. The most significant finding was that antibody titers to the viral capsid antigen of EBV were elevated (greater than or equal to 1:320) in 39% of the cases and in only 14% of the sibling-controls; the relative risk adjusted for age and sex was 4.1. The geometric mean titer was three-fold higher among cases (175.6 vs. 58.1) Subjects who reported a history of IM had a higher distribution of titers than those who did not. Cases also had elevated titers against the early antigen of EBV - the D Component being most prominent. A significantly higher proportion of cases has elevated titers against CMV, relative risk = 3.4, but the prevalence of CMV antibody was relatively low and not consistently higher among cases. The findings support the hypothesis that EBV may play a role in the pathogenesis of HD among persons with elevated titers. The findings neither confirm nor deny a possible role of CMV.