gebhart/patrepeval huggingface dataset:
Industrializing Structural Biology (2001)

X-ray crystallography is the method of choice for determining molecular structure. The accumulation of molecular structure information has allowed a more complete representation of three-dimensional protein folds, enabling more successful homology modeling of unknown structures. Breakthroughs in genome sequencing projects have underscored the need for concomitant advances in structural biology if we hope to determine the extent of protein folding-space and elucidate how an assembly of proteins constitutes a cellular organism. This essay outlines an industrial approach to high-throughput (HT) determination of molecular structures.
A Complex Program of Striatal Gene Expression Induced by Dopaminergic Stimulation (1998)

Dopamine acting in the striatum is necessary for normal movement and motivation. Drugs that change striatal dopamine neurotransmission can have long-term effects on striatal physiology and behavior; these effects are thought to involve alterations in gene expression. Using the 6-hydroxydopamine lesion model of Parkinson's disease and differential display PCR, we have identified a set of more than 30 genes whose expression rapidly increases in response to stimulation of striatal dopamine D1 receptors. The induced mRNAs include both novel and previously described genes, with diverse time courses of expression. Some genes are expressed at near-maximal levels within 30 min, whereas others show no substantial induction until 2 hr or more after stimulation. Some of the induced genes, such as CREM, CHOP, and MAP kinase phosphatase-1, may be components of a homeostatic response to excessive stimulation. Others may be part of a genetic program involved in cellular and synaptic plasticity. A very similar set of genes is induced in unlesioned animals by administration of the psychostimulant cocaine or the antipsychotic eticlopride, although in distinct striatal cell populations. In contrast to some previously described early genes, most of the novel genes are not induced in cortex by apomorphine, indicating specificity of induction. Thus we have identified novel components of a complex, coordinated genetic program that is induced in striatal cells in response to various dopaminergic manipulations.
Cluster architectures and S/390 Parallel Sysplex scalability (1997)

Supporting high transaction rates and high availability for on-line transaction processing and emerging applications requires systems consisting of multiple computing nodes. We outline various cluster architectures and describe the factors that motivate the S/390® Parallel Sysplex™ architecture and its resulting advantages. We quantify the scalability of the S/390 Parallel Sysplex and show that the transaction rate supported is close to linear as nodes are added to the system. The key facet of the S/390 Parallel Sysplex architecture is the coupling facility. The coupling facility provides for very efficient intertransaction concurrency control, buffer cache coherency control, and shared buffer management, among other functions, that lead to the excellent scalability achieved. It also provides for effective dynamic load balancing, high data buffer hit ratios, and load balancing after a failure.
Proteolytic Cleavage Governs Interleukin-11 Trans-signaling (2016)

Interleukin (IL)-11 has been shown to be a crucial factor for intestinal tumorigenesis, lung carcinomas, and asthma. IL-11 is thought to exclusively mediate its biological functions through cell-type-specific expression of the membrane-bound IL-11 receptor (IL-11R). Here, we show that the metalloprotease ADAM10, but not ADAM17, can release the IL-11R ectodomain. Chimeric proteins of the IL-11R and the IL-6 receptor (IL-6R) revealed that a small juxtamembrane portion is responsible for this substrate specificity of ADAM17. Furthermore, we show that the serine proteases neutrophil elastase and proteinase 3 can also cleave the IL-11R. The resulting soluble IL-11R (sIL-11R) is biologically active and binds IL-11 to activate cells. This IL-11 trans-signaling pathway can be inhibited specifically by the anti-inflammatory therapeutic compound sgp130Fc. In conclusion, proteolysis of the IL-11R represents a molecular switch that controls the IL-11 trans-signaling pathway and widens the number of cells that can be activated by IL-11.
Posicionamiento y proyección actual del motor de paso en aplicaciones industriales. (2002)

Resumen es: El presente trabajo aborda el empleo del motor de paso en las aplicaciones industriales actuales, los recientes avances y tendencias en la construccion d...
Suppression of Inflammatory Cytokine Production by Carbon Monoxide Involves the JNK Pathway and AP-1 (2003)

The stress-inducible protein heme oxygenase-1 provides protection against oxidative stress and modulates pro-inflammatory cytokines. As the sepsis syndrome results from the release of pro-inflammatory mediators, we postulated that heme oxygenase-1 and its enzymatic product CO would protect against lethality in a murine model of sepsis. Mice treated with a lethal dose of lipopolysaccharide (LPS) and subsequently exposed to inhaled CO had significantly better survival and lower serum interleukin (IL)-6 and IL-1beta levels than their untreated counterparts. In vitro, mouse macrophages exposed to LPS and CO had significantly attenuated IL-6 production; this effect was concentration-dependent and occurred at a transcriptional level. The same effect was seen with increased endogenous CO production through overexpression of heme oxygenase-1. Mutation within the AP-1-binding site in the IL-6 promoter diminished the effect of CO on promoter activity, and treatment of macrophages with CO decreased AP-1 binding in an electrophoretic mobility shift assay. Electrophoretic mobility supershift assay indicated that the JunB, JunD, and c-Fos components of AP-1 were particularly affected. Upstream of AP-1, CO decreased JNK phosphorylation in murine macrophages and lung endothelial cells. Mice deficient in the JNK pathway had decreased serum levels of IL-6 and IL-1beta in response to LPS compared with control mice, and no effect of CO on these cytokine levels was seen in Jnk1 or Jnk2 genedeleted mice. In summary, these results suggest that CO provides protection in a murine model of sepsis through modulation of inflammatory cytokine production. For the first time, the effect of CO is shown to be mediated via the JNK signaling pathway and the transcription factor AP-1.
The Asialoglycoprotein Receptor Mediates Hepatic Binding and Uptake of Natural Hepatitis B Virus Particles Derived From Viraemic Carriers (1994)

As a putative mechanism of hepatitis B virus (HBV) uptake into hepatocytes the interaction between HBV and the hepatic, human-derived asialoglycoprotein receptor (ASGPR) was investigated. Sera from patients with different variations of hepatitis B surface antigen-(HBsAg) positive chronic hepatitis, HBV particles isolated from HBV carriers with high-titre viraemia and commercial HBsAg served as sources of HBV. ASGPR was affinity-purified from human liver. HBV that had bound to isolated ASGPR was either detected by radioimmunoassay using solid-phase bound ASGPR or enzyme immunoassay with biotin-ASGPR bound to immobilized HBV. Furthermore, binding and uptake of purified, 125I-labelled HBV particles into human hepatoma cell lines (HepG2 and HuH7), which constitutively express functional ASGPR molecules, were compared to that of ASGPR-negative COS cells. As a result HBV was found to bind to purified human ASGPR in two different assays. Circulating virus particles from sera with high titre viraemia showed the highest attachment activity to ASGPR. HBV binding to purified ASGPR was saturable and inhibitable by an excess of D-galactose-bearing ligands, by EDTA and anti-receptor immunoglobulin. Lysis of particles by adding detergent abolished immunodetectable HBV binding to purified ASGPR. Commercial HBsAg did not adhere to solid phase-immobilized ASGPR. Monoclonal anti-preS1 antibody (MA18/7) but not anti-preS2 antibody (Q19/10) inhibited virus attachment. Purified and radiolabelled HBV particles showed binding to HepG2 and HuH7 cells but to much lesser degree to COS cells. Cellular binding of HBV was significantly inhibited by blocking of ASGPR function. Both ASGPR ligands and rabbit anti-ASGPR immunoglobulin but not non-immune rabbit serum inhibited uptake of radiolabelled HBV particles into HepG2 cells or HuH7 cells, respectively. This study suggests that HBV virions may enter human hepatocytes via ASGPR molecules by attachment of viral preS1-related envelope binding sites to this receptor.
Reduction of Target Gene Expression by a Modified U1 snRNA (2001)

Although the primary function of U1 snRNA is to define the 5' donor site of an intron, it can also block the accumulation of a specific RNA transcript when it binds to a donor sequence within its terminal exon. This work was initiated to investigate if this property of U1 snRNA could be exploited as an effective method for inactivating any target gene. The initial 10-bp segment of U1 snRNA, which is complementary to the 5' donor sequence, was modified to recognize various target mRNAs (chloramphenicol acetyltransferase [CAT], beta-galactosidase, or green fluorescent protein [GFP]). Transient cotransfection of reporter genes and appropriate U1 antitarget vectors resulted in >90% reduction of transgene expression. Numerous sites within the CAT transcript were suitable for targeting. The inhibitory effect of the U1 antitarget vector is directly related to the hybrid formed between the U1 vector and target transcripts and is dependent on an intact 70,000-molecular-weight binding domain within the U1 gene. The effect is long lasting when the target (CAT or GFP) and U1 antitarget construct are inserted into fibroblasts by stable transfection. Clonal cell lines derived from stable transfection with a pOB4GFP target construct and subsequently stably transfected with the U1 anti-GFP construct were selected. The degree to which GFP fluorescence was inhibited by U1 anti-GFP in the various clonal cell lines was assessed by fluorescence-activated cell sorter analysis. RNA analysis demonstrated reduction of the GFP mRNA in the nuclear and cytoplasmic compartment and proper 3' cleavage of the GFP residual transcript. An RNase protection strategy demonstrated that the transfected U1 antitarget RNA level varied between 1 to 8% of the endogenous U1 snRNA level. U1 antitarget vectors were demonstrated to have potential as effective inhibitors of gene expression in intact cells.
Radiation/Paclitaxel Treatment of p53-Abnormal Non-Small Cell Lung Cancer Xenograft Tumor and Associated Mechanism (2012)

Our study suggested that a PTEN-PI3K-Akt-Bax signaling cascade is involved in the therapeutic effect of combined radiation/paclitaxel treatment in NSCLC without p53 expression. Our study also suggested that PTEN is an ideal target in tumors with wild-type PTEN and a lack of functional p53.
An overview of biotechnological production of propionic acid: From upstream to downstream processes (2017)

The increasing demand for propionic acid (PA) production and its wide applications in several industries, especially the food industry (as a preservative and satiety inducer), have led to studies on the low-cost biosynthesis of this acid. This paper gives an overview of the biotechnological aspects of PA production and introduces Propionibacterium as the most popular organism for PA production. Moreover, all process variables influencing the production yield, different simple and complex carbon sources, the metabolic pathway of production, engineered mutants with increased productivity, and modified tolerance against high concentrations of acid have been described. Furthermore, possible methods of extraction and analysis of this organic acid, several applied bioreactors, and different culture systems and substrates are introduced. It can be concluded that maximum biomass and PA production may be achieved using metabolically engineered microorganisms and analyzing the most significant factors influencing yield. To date, the maximum reported yield for PA production is 0.973 g·g-1, obtained from Propionibacterium acidipropionici in a three-electrode amperometric culture system in medium containing 0.4 mM cobalt sepulchrate. In addition, the best promising substrate for PA bioproduction may be achieved using glycerol as a carbon source in an extractive continuous fermentation. Simultaneous production of PA and vitamin B12 is suggested, and finally, the limitations of and strategies for competitive microbial production with respect to chemical process from an economical point of view are proposed and presented. Finally, some future trends for bioproduction of PA are suggested.
Induction of sarcomas by mutant IDH2 (2013)

More than 50% of patients with chondrosarcomas exhibit gain-of-function mutations in either isocitrate dehydrogenase 1 (IDH1) or IDH2. In this study, we performed genome-wide CpG methylation sequencing of chondrosarcoma biopsies and found that IDH mutations were associated with DNA hypermethylation at CpG islands but not other genomic regions. Regions of CpG island hypermethylation were enriched for genes implicated in stem cell maintenance/differentiation and lineage specification. In murine 10T1/2 mesenchymal progenitor cells, expression of mutant IDH2 led to DNA hypermethylation and an impairment in differentiation that could be reversed by treatment with DNA-hypomethylating agents. Introduction of mutant IDH2 also induced loss of contact inhibition and generated undifferentiated sarcomas in vivo. The oncogenic potential of mutant IDH2 correlated with the ability to produce 2-hydroxyglutarate. Together, these data demonstrate that neomorphic IDH2 mutations can be oncogenic in mesenchymal cells.
InP@ZnSeS, Core@Composition Gradient Shell Quantum Dots with Enhanced Stability (2011)

Utilizing the reactivity difference between TOPSe and TOPS, we synthesized InP@ZnSeS QDs with the composition gradient in a radial direction where ZnSe alleviated lattice strain and ZnS protected QDs from degradation so that we achieved QDs with high QE and photo/chemical stability. In terms of systematic investigation on the relationship between the shell nanostructure and QD stability, we demonstrated that QDs with thick gradient shells exhibited high QE and much enhanced stability against the shell degradation under UV irradiation, ligand exchange, or rigorous purification. This enhanced stability of InP@ZnSeS QDs is attributed to the improved uniformity of composition gradient shells, the efficient confinement of exciton wavefunctions, and the minimized surface oxidation and non-radiative decay via surface states generated by photo-oxidation or ligand exchange. Using InP@ZnSeS QDs with enhanced stability, we were able to demonstrate InP-based colloidal green-emitting QD-LEDs. Although the current status of InP@ZnSeS QDs is not fully optimized to realize practical optoelectronic devices, the approach taken in the present study (i.e., the composition gradient shell structure naturally made from reactivity difference in precursors) will give clues to facilitate the synthesis of InP QDs with advanced nanostructures.
Safety and Tolerance of Lactobacillus reuteri in Healthy Adult Male Subjects (1995)

Thirty healthy, male subjects (age 18 to 75 yrs) were used in a two-group, double-blinded, parallel design to evaluate the safety and tolerance of a potential probiotic organism, Lactobacillus reuteri. Subjects (15/treatment) consumed two gelatin capsules daily for 21 d that contained either a freeze dried L. reuteri preparation in a cryoprotectant, or a placebo (cryoprotectant). The concentration of L. reuteri was such that subjects consumed 1 × 1011 CFU per day. The study was 28 d in length with daily documentation of the presence of gastrointestinal symptoms (nausea, diarrhoea, cramping, distention, flatulence, vomiting, constipation, burping and reflux). In addition, serum chemistries, haematology, urinalysis, urinary indican excretion, and faecal microbiota (L. reuteri and total Lactobacillus spp. enumeration) were measured weekly (day 0, 7, 14, 21 and 28). A physical exam was given on day 0, 21, and 28. An additional faecal sample was obtained on day 77 for microbial enumeration. Subjects could consume their regular diets; however, alcohol was not allowed. Physical exam and urinalysis parameters were not clinically different between treatments. Supplemental L. reuteri reduced (P < 0.05) urinary indican excretion at day 7, but had no effect (P > 0.05) on subsequent urine collections. Although significant differences were observed for a few of the serum chemistry and haematology variables, all of the values remained within the expected normal range for healthy adult males. Subjects consuming supplemental L. reuteri had increased (P < 0.01) levels of L. reuteri in their faeces on day 7, 14, 21, and 28. However, colonisation was lost within 2 mths of termination of L. reuteri consumption (day 77). Levels of total Lactobacillus spp. never differed (P > 0.05) between treatments; however, the ratio of L. reuteri: total Lactobacillus spp. increased (P < 0.05) for subjects consuming supplemental L. reuteri. Incidence of subjective tolerance factors was infrequent and similar for both treatments. In conclusion, supplemental L. reuteri may be fed at 1 × 1011 CFU/day without any clinically significant safety or tolerance problems. Intake of L. reuteri (1 × 1011 CFU/day) results in colonisation (as measured by faecal level) within 7 d of consumption and is maintained for at least 7 d post consumption; however, colonisation is lost within 2 mths of washout.
Biosynthesis and Regulation of Immunoglobulins (1983)

Immunoglobulin gene expression exhibits a number of intriguing regulatory features. Immunoglobulin genes undergo dynamic DNA rearrangements and somatic mutations. The expression of immunoglobulin genes exhibits allelic exclusion and isotypic exclusion. The developmental regulation of immunoglobulin gene expression during B cell differentiation is character­ ized by (a) the differential onset of heavy and light chain production, (b) great changes in the level of expression, and (c) transition from the insertion of immunoglobulin as antigen receptors in the lymphocyte membrane to its active secretion. Darnell (40, 41) and Brown (27) have recently reviewed the variety of transcriptional, post-transcriptional (e.g. RNA processing), and transla­ tional mechanisms employed in the regulation of eukaryotic gene expres­ sion. This review summarizes recent progress towards understanding the molecular mechanisms in immunoglobulin gene expression and regulation in the context of the developments in other eukaryotic genes. The complex array of lymphoid cell and lymphokine factor interactions that affect im­ munoglobulin gene expression are not considered here.
Image distortion in multimode fibers and restoration by polarization-preserving phase conjugation (1987)

Image restoration after a double pass through a multimode fiber using a polarization-preserving phase conjugator is demonstrated. Results indicate that the resolution of the restored image is limited by the number of guided modes and that the contrast is restored only when the phase conjugator preserves polarization on reflection.
CD4+ T Cells Elicit Host Immune Responses to MHC Class II− Ovarian Cancer through CCL5 Secretion and CD40-Mediated Licensing of Dendritic Cells (2010)

T cell adoptive transfer strategies that have produced clinical remissions against specific tumors have so far produced disappointing results against ovarian cancer. Recent evidence suggests that adoptively transferred CD4(+) T cells can trigger endogenous immune responses in particular patients with ovarian cancer through unknown mechanisms. However, conflicting reports suggest that ovarian cancer-infiltrating CD4(+) T cells are associated with negative outcomes. In this study, we elucidate the phenotypic attributes that enable polyclonal CD4(+) T cells briefly primed against tumor Ags to induce therapeutically relevant endogenous antitumor immune responses. Our results unveil a therapeutic mechanism whereby tumor-primed CD4(+) T cells transferred into ovarian cancer-bearing mice secrete high levels of CCL5, which recruits endogenous CCR5(+) dendritic cells to tumor locations and activate them through CD40-CD40L interactions. These newly matured dendritic cells are then able to prime tumor-specific endogenous CD8(+) T cells, which mediate long-term protection. Correspondingly, administration of tumor-primed CD4(+) T cells significantly delayed progression of MHC class II(-) ovarian cancers, similarly to CD8(+) T cells only, and directly activated wild-type but not CD40-deficient dendritic cells recruited to the tumor microenvironment. Our results unveil a CCL5- and CD40L-dependent mechanism of transferring immunity from exogenously activated CD4(+) T cells to tumor-exposed host cells, resulting in sustained antitumor effects. Our data provide a mechanistic rationale for incorporating tumor-reactive CD4(+) T cells in adoptive cell transfer immunotherapies against ovarian cancer and underscore the importance of optimizing immunotherapeutic strategies for the specific microenvironment of individual tumors.
Development of Spontaneous Airway Changes Consistent with Human Asthma in Mice Lacking T-bet (2002)

Human asthma is associated with airway infiltration by T helper 2 (TH2) lymphocytes. We observed reduced expression of the TH1 transcription factor, T-bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4+ cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma. Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma.
Role of testosterone on pain threshold in rats. (1995)

Pain thresholds were recorded in rats by progressive increase in electrical stimulation to induce tail withdrawal, vocalisation and vocalisation after discharge. It was observed that castration resulted in significant reduction of pain threshold which however returned to normal level on substitution with testosterone therapy.