gebhart/patrepeval huggingface dataset:
The p38 Mitogen-Activated Protein Kinase Is Involved in Associative Learning in Rabbits (2001)

This study examined the role of the mitogen-activated protein kinase (MAPK) family during acquisition of the rabbit's classically conditioned eye-blink response. Eye-blink conditioning produced a significant, bilateral activation of both extracellular signal-regulated protein kinases (ERKs) and p38 MAPK in the anterior cerebellar vermis. There was also a significant bilateral activation of ERKs in the dorsal hippocampus with no change in p38 MAPK. These changes were seen at 2 min after the last conditioning session, were maintained for at least 180 min, and occurred without any change in the protein expression of either ERKs or p38 MAPK. There were no changes in ERKs or p38 MAPK in frontal cortex, in cerebellar hemispheral lobule VI, or in a section of brainstem containing the inferior olive. Moreover, the stress-related protein kinase Jun N-terminal kinase (JNK), another subfamily of MAPKs, was not altered in any of the brain regions examined. Animals receiving explicitly unpaired presentations of a conditioned stimulus and an unconditioned stimulus did not acquire conditioned responses (CRs) and did not demonstrate any changes in ERKs, p38 MAPK, or JNK. The intraventricular injection of SB203580, a selective p38 MAPK inhibitor, significantly retarded CR acquisition and blocked the learning-related increases in p38 MAPK activity in the anterior vermis. PD98059, a selective MAPK kinase inhibitor, had a smaller and only marginally significant effect on CR acquisition, although it did block the learning-related increases in ERK activity in both the hippocampus and anterior vermis. These results indicate that p38 MAPK is activated during associative learning and may play a role in the transcriptional events that lead to memory consolidation.
Signal transduction through NF-κB (1998)

The inducible transcription factor NF-κB plays a central role in the regulation of many immune and inflammatory responses. Advances in our knowledge of the signaling mechanisms that control the activation of NF-κB and recent insights into the nature of the IκB-kinase represent significant steps forward in understanding this important signaling pathway.
The effect of triethylenetetramine dihydrochloride on the in vivo susceptibility of Pseudomonas aeruginosa to gentamicin. (1979)

A chelating agent, triethylenetetramine dihydrochloride (TRIEN dihydrochloride) increased the efficacy of gentamicin in vivo against a clinical isolate of P. aeruginosa, designated Ps 15. Mice which were inoculated with 10 X LD50 of Ps 15 and treated with doses of 2 approximately 16 mg of gentamicin per kg per day all died. However, treatment with 8 mg of gentamicin per kg body weight per day plus 30 mg of Trien dihydrochloride per day markedly reduced the mortality. The combined therapy also reduced the number of viable organisms that accumulated in the kidney during a 24-hour period post inoculation. When a dosage level of 8 mg of gentamicin was exceeded in the combined treatment regimen, all of the infected mice died, and a high concentration of endotoxin could be detected in the mouse sera by the limulus assay.
Solving and analyzing side-chain positioning problems using linear and integer programming (2004)

We present an integer linear programming (ILP) formulation of side-chain positioning that allows us to tackle large problem sizes. We relax the integrality constraint to give a polynomial-time linear programming (LP) heuristic. We apply LP to position side chains on native and homologous backbones and to choose side chains for protein design. Surprisingly, when positioning side chains on native and homologous backbones, optimal solutions using a simple, biologically relevant energy function can usually be found using LP. On the other hand, the design problem often cannot be solved using LP directly; however, optimal solutions for large instances can still be found using the computationally more expensive ILP procedure. While different energy functions also affect the difficulty of the problem, the LP/ILP approach is able to find optimal solutions. Our analysis is the first large-scale demonstration that LP-based approaches are highly effective in finding optimal (and successive near-optimal) solutions for the side-chain positioning problem.
Evidence for protein 4.1B acting as a metastasis suppressor (2007)

We compared a non-metastasising sarcoma cell population with three related populations of increasing metastatic potential. The metastatic cells in vitro exhibited a significantly reduced incidence of actin stress fibres but enhanced motility and chemotaxis. We also investigated gene expression underlying progression to a metastatic phenotype by performing a microarray analysis of the four sarcoma populations. We identified a subset of genes with significantly altered expression levels between non-metastasising and metastasising cells in tissue culture and in primary tumours. One such gene, encoding protein 4.1B, is downregulated in the metastatic sarcoma populations. To investigate possible roles of 4.1B in the mechanisms of metastasis, we used RNA interference (RNAi) to reduce its expression in the non-metastatic cells. Cells with reduced 4.1B expression displayed an altered F-actin morphology, with significantly fewer stress fibres. We also found that the 4.1B RNAi cells migrated at twice the speed of the untreated cells. Metastatic cells exogenously expressing 4.1B migrated at half the speed of control metastatic cells and displayed suppressed chemotaxis. Therefore, we propose that the reduction of 4.1B in the metastatic cells promotes the metastatic phenotype as a result of inducing a loss of actin stress fibres and a concomitant increase in cell motility.
Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. (1987)

We have previously shown that at least two types of Lyt-1+, Lyt-2-, L3T4+ helper T cell clones can be distinguished in vitro by different patterns of lymphokine secretion and by different forms of B cell help. Evidence is presented here to show that one type of helper T cell clone (TH1) causes delayed-type hypersensitivity (DTH) when injected with the appropriate antigen into the footpads of naive mice. The antigen-specific, major histocompatability complex (MHC)-restricted footpad swelling reaction peaked at approximately 24 hr. Footpad swelling was induced by all TH1 clones tested so far, including clones specific for soluble, particulate, or allogeneic antigens. In contrast, local transfer of TH2 cells and antigen did not produce a DTH reaction, even when supplemented with syngeneic spleen accessory cells. Similarly, local transfer of an alloreactive cytotoxic T lymphocyte clone into appropriate recipients did not produce DTH. The requirements for the DTH reaction induced by TH1 cells were investigated further by using TH1 clones with dual specificity for both foreign antigens and M1s antigens. Although these clones responded in vitro to either antigen + syngeneic presenting cells, or M1s disparate spleen cells, they responded in vivo only to antigen + MHC and did not cause footpad swelling in an M1s-disparate mouse in the absence of antigen. Moreover, in vitro preactivation of TH1 or TH2 cells with the lectin concanavalin A was insufficient to induce DTH reactions upon subsequent injection into footpads. From these results, we conclude that the lack of DTH given by TH2 clones in vivo could be due to the inability of the TH2 cells to produce the correct mediators of DTH, or to a lack of stimulation of TH2 clones in the footpad environment.
Expression Profile of Two Storage-Protein Gene Families in Hexaploid Wheat Revealed by Large-Scale Analysis of Expressed Sequence Tags (2005)

To discern expression patterns of individual storage-protein genes in hexaploid wheat (Triticum aestivum cv Chinese Spring), we analyzed comprehensive expressed sequence tags (ESTs) of common wheat using a bioinformatics technique. The gene families for alpha/beta-gliadins and low molecular-weight glutenin subunit were selected from the EST database. The alignment of these genes enabled us to trace the single nucleotide polymorphism sites among both genes. The combinations of single nucleotide polymorphisms allowed us to assign haplotypes into their homoeologous chromosomes by allele-specific PCR. Phylogenetic analysis of these genes showed that both storage-protein gene families rapidly diverged after differentiation of the three genomes (A, B, and D). Expression patterns of these genes were estimated based on the frequencies of ESTs. The storage-protein genes were expressed only during seed development stages. The alpha/beta-gliadin genes exhibited two distinct expression patterns during the course of seed maturation: early expression and late expression. Although the early expression genes among the alpha/beta-gliadin and low molecular-weight glutenin subunit genes showed similar expression patterns, and both genes from the D genome were preferentially expressed rather than those from the A or B genome, substantial expression of two early expression genes from the A genome was observed. The phylogenetic relationships of the genes and their expression patterns were not correlated. These lines of evidence suggest that expression of the two storage-protein genes is independently regulated, and that the alpha/beta-gliadin genes possess novel regulation systems in addition to the prolamin box.
Einführung (2004)

Vor dem Hintergrund eines zunehmend liberalisierten Welthandels und vereinfachter weltweiter Ressourcentransfers ist die globale Geschäftstätigkeit für viele Unternehmen zum Schlüsselfaktor ihres Erfolges geworden. Als seit langem empirisch feststellbares Phänomen kann die Internationalisierung von Unternehmen dabei gerade in den letzten beiden Dekaden besondere Zuwachsraten verzeichnen.1 So ist seit Mitte der 80er Jahre ein starkes Wachstum des Welthandels zu verzeichnen.2 Daneben haben sich die weltweiten Direktinvestitionsbestände in den 80er und 90er Jahren stark erhöht und werden inzwischen auf mehr als 6,5 Billionen US-$ geschätzt, was im Vergleich zu 1980 etwa eine Verzwölffachung bedeutet.3
Clinical applications of arterial stiffness; definitions and reference values (2002)

Arterial stiffening is the most important cause of increasing systolic and pulse pressure, and for decreasing diastolic pressure beyond 40 years of age. Stiffening affects predominantly the aorta and proximal elastic arteries, and to a lesser degree the peripheral muscular arteries. While conceptually a Windkessel model is the simplest way to visualize the cushioning function of arteries, this is not useful clinically under changing conditions when effects of wave reflection become prominent. Many measures have been applied to quantify stiffness, but all are approximations only, on account of the nonhomogeneous structure of the arterial wall, its variability in different locations, at different levels of distending pressure, and with changes in smooth muscle tone. This article summarizes the methods and indices used to estimate arterial stiffness, and provides values from a survey of the literature, followed by recommendations of an international group of workers in the field who attended the First Consensus Conference on Arterial Stiffness, which was held in Paris during 2000, under the chairmanship of M.E. Safar and E.D. Frohlich.
scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair. (1991)

C.B-17 severe combined immunodeficient (scid) mice carry the scid mutation and are severely deficient in both T cell- and B cell-mediated immunity, apparently as a result of defective V(D)J joining of the immunoglobulin and T-cell receptor gene elements. In the present studies, we have defined the tissue, cellular, and molecular basis of another characteristic of these mice: their hypersensitivity to ionizing radiation. Bone marrow stem cells, intestinal crypt cells, and epithelial skin cells from scid mice are 2- to 3-fold more sensitive when irradiated in situ than are congenic BALB/c or C.B-17 controls. Two independently isolated embryo fibroblastic scid mouse cell lines display similar hypersensitivities to gamma-rays. In addition, these cell lines are sensitive to cell killing by bleomycin, which also produces DNA strand breaks, but not by the DNA crosslinking agent mitomycin C or UV irradiation. Measurement of the rejoining of gamma-ray-induced DNA double-strand breaks by pulsed-field gel electrophoresis indicates that these animals are defective in this repair system. This suggests that the gamma-ray sensitivity of the scid mouse fibroblasts could be the result of reduced repair of DNA double-strand breaks. Therefore, a common factor may participate in both the repair of DNA double-strand breaks as well as V(D)J rejoining during lymphocyte development. This murine autosomal recessive mutation should prove extremely useful in fundamental studies of radiation-induced DNA damage and repair.
Transmembrane signaling by the high-affinity IgE receptor on membrane preparations. (1992)

Aggregating the receptor with high affinity for IgE (Fc epsilon RI) stimulates a variety of phenomena in mast cells. Previous efforts to reproduce some of these events in broken-cell preparations such as isolated membranes have had limited success, possibly because the phenomena being monitored were too distal from the initial events. One of the earliest responses is now known to be the phosphorylation of tyrosine residues on several proteins, including the beta and gamma subunits of Fc epsilon RI. We show that in cell sonicates or on partially purified membranes derived from tumor mast cells, aggregating Fc epsilon RI stimulates phosphorylation of receptor tyrosine residues. As in the intact cells, receptor-mediated phosphorylation occurs only on receptors that are themselves aggregated. Because even in the unfractionated sonicates the phosphorylation of other cellular components was not detectably enhanced, and because the evidence is against the receptor itself being a kinase, our results suggest that phosphorylation of Fc epsilon RI is one of the earliest events stimulated by the receptor--an event that can now be investigated on simpler biological preparations than previously available.
Conducting bio-materials based on gellan gum hydrogels (2009)

Hydrogels, a class of highly hydrated polymer materials, are emerging as a viable bio-material for tissue engineering applications due to their bio-degradability, process-ability, and similarity with the natural extra-cellular matrix. Here, we report on gellan gum hydrogels and demonstrate that the gelation temperature can be tailored to be physiologically relevant. Furthermore, we demonstrate the biocompatibility of these hydrogels and show that cell behaviour is influenced by gel modulus and the incorporation of surface topographical features. Carbon nanotubes were incorporated into hydrogels as conducting fillers to achieve an electrically conducting hydrogel for the future purpose of electrical cell stimulation. Percolation studies revealed that a carbon nanotube concentration of 1.3% by weight is required to achieve electrical conduction through the hydrogel.
The importance of genetic diagnosis for Duchenne muscular dystrophy (2016)

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy are caused by mutations in the dystrophin-encoding DMD gene. Large deletions and duplications are most common, but small mutations have been found as well. Having a correct diagnosis is important for family planning and providing proper care to patients according to published guidelines. With mutation-specific therapies under development for DMD, a correct diagnosis is now also important for assessing whether patients are eligible for treatments. This review discusses different mutations causing DMD, diagnostic techniques available for making a genetic diagnosis for children suspected of DMD and the importance of having a specific genetic diagnosis in the context of emerging genetic therapies for DMD.
Experimental carotid thrombosis in the guinea pig. (1994)

The aim of our study was to develop a new carotid thrombosis model with an arterial shear rate close to that prevailing in affected arteries of patients with transient ischemic attacks (TIAs) and moderate carotid stenosis and to test various antithrombotic principles. In anaesthetized guinea pigs, carotid blood flow was monitored by a Doppler flow probe and the vessel was damaged by 2 or 3 brief pinches by a surgical forceps. The intravenous effects of aspirin (20 mg/kg), heparin (200 U/kg) and hirudin (500 micrograms/kg) or Ro 44-9883 (0.2 to 1 mg/kg), a new selective non-peptidic GP IIb-IIIa inhibitor were tested. After the damage, blood flow progressively decreased to zero and could regularly and reproducibly be restored by a mechanical shaking of the artery. The occlusive thrombus consisted mainly of platelet aggregates. The estimated shear rate in the damaged carotid artery was in the range of 1500 to 2800 s-1. The resulting cyclic flow variations (CFVs) were obtained in all the guinea pigs and were abolished in 10%, 20% and 60% of the animals treated with heparin, hirudin and aspirin, respectively. Ro 44-9883 abolished dose dependently the CFVs with 100% abolition at 1 mg/kg. Thus reproducible thrombosis without additional stenosis can be generated in the carotid artery of the guinea pig at a lower shear rate than that prevailing in the classical thrombosis models. GPIIb-IIIa blockade showed a higher curative efficacy than inhibition of the cyclooxygenase pathway or that of thrombin generation either through an antithrombin III dependent or independent mechanism.
Surface Modification of Carbon Microbead by the Grafting of Polymers (1995)

Abstract The surface grafting of polymers onto carbon microbead, a sphere of carbonized phenol resin, was achieved by two methods: 1) the radical graft polymerization initiated by azo groups introduced onto the surface and 2) the trapping of polymer radicals by a carbon microbead surface. The introduction of azo groups onto a carbon microbead surface was achieved by the reaction of surface carboxyl groups on the bead with 2,2′-azobis[2-(hydroxymethyl)-propionitrile] using N, N′-dicyclohexyl-carbodiimide as a condensing agent. The radical polymerization of methyl methacrylate (MMA) was initiated by surface azo groups introduced onto the surface, and polyMMA was grafted onto the bead through the propagation of polymer chains from the surface: the percentage of grafting reached to 18% after 16 hours. Furthermore, it was found that by the reaction of an azo polyamide (a polyamide having an azo bond in the main chain) and peroxide polymers (polymers having peroxide groups in the main chain and/or pendant group) with carbon microbead at 70–110°C, polymer radicals formed by the thermal decomposition of these azo and peroxide polymers gave the corresponding polymer-grafted carbon microbead. The percentage of grafting decreased with increasing molecular weight of the polymer radicals. It was found that the reactivity of surface functional groups and polycondensed aromatic rings on carbon microbead are analogous with those of a carbon-black surface.
Studies of the cellulolytic system of Trichoderma reesei QM 9414 (1985)

The 1,4-beta-glucan cellobiohydrolase II (CBH II) from Trichoderma reesei QM 9414 catalyses the hydrolysis of the 4-methylumbelliferyl beta-D-glycosides derived from cellotriose, cellotetraose and cellopentaose [MeUmb(Glc)n; n = 3 - 5]. The reaction has been followed by quantitative high-performance liquid chromatography. Specific activity for cellobiose removal at apparent substrate saturation were determined as (0.8 +/- 0.2) min-1 for MeUmb(Glc)3 and (9 +/- 2) min-1 for MeUmb(Glc)4. The enzyme showed a deviant specificity with MeUmb(Glc)5 as substrate. Two chromophoric products were formed simultaneously [MeUmb(Glc)3 and MeUmb(Glc)2] with turn-over numbers (17 +/- 4) min-1 and (21 +/- 6) min-1, respectively. Methylumbelliferyl beta-glucoside (MeUmbGlc) and the corresponding cellobioside [MeUmb(Glc)2] were used in equilibrium binding experiments. Both ligands yielded one binding site per molecule of Mr = 54000 upon forced flow dialysis (diafiltration). The association constants found were in fair agreement with those determined from MeUmb fluorescence quenching titrations. Quenching was total at all temperatures investigated for MeUmb(Glc)2, whereas for MeUmbGlc it increased from 80% to 100% between 2 degrees C and 20 degrees C. The association constants fitted linear van't Hoff plots in both cases. MeUmb(Glc)2 and MeUmbGlc were also used as indicator ligands to determine the association constants and thermodynamic parameters of several non-chromophoric ligands of CBH II. The binding of glucose increased the affinity for MeUmb(Glc)2 whereas it displaced MeUmbGlc from its complex. A putative binding site of the CBH II containing four subsites can be proposed. The thermodynamic data for methyl beta-D-glucopyranoside and cellobiose as ligands also point at an extended binding site.
Studies with positron emission tomography after systemic administration of fluorine-18-uracil in patients with liver metastases from colorectal carcinoma. (1993)

Fluorouracil (FU) is the most common cytostatic agent used for chemotherapy in patients with colorectal tumors. Fifty patients with 78 hepatic metastases from colorectal tumors were examined with positron emission tomography (PET) following intravenous infusion of 18F-FU. The uptake of the cytostatic agent was evaluated in normal liver parenchyma, liver metastases and the aorta. Tracer uptake was expressed with the standardized uptake value (SUV). The maximum liver activity was 11.3 SUV (mean value) with a standard deviation of 1.85 SUV. The highest activity concentrations were noted 30 min (mean value) postinjection. In comparison, the activity concentration of individual metastasis was low. Two hours after tracer injection, the mean activity in metastases was 1.3 SUV, but notable individual variation in uptake was seen. Fluorine-18 concentration values 2 hr after FU infusion were approximately 44% of the FU uptake 20 min postinfusion. Fifty-three metastases were also examined with 15O-labeled water. The examination was performed to compare the uptake of the nonmetabolized tracer with FU uptake. We noted a statistically significant correlation between 15O-water concentration, uptake of nonmetabolized FU 8 min after the end of the infusion and FU retention (120 min postinjection) in a subgroup of metastases. The results suggest that FU retention in different metastases is highly variable and mainly dependent on early FU uptake into tumor cells.
Characterization of interleukin 2-dependent cytotoxic T-cell clones: specificity, cell surface phenotype, and susceptibility to blocking by Lyt antisera. (1983)

Cytotoxic T-cells were derived from the peritoneal cavity of a C57BL/6 mouse immunized with BALB/c sarcoma Meth A and from the spleens of BALB/c x C57BL/6 F1 (hereafter called CB6F1) mice immunized with BALB/c leukemia RL male 1. The cells were cultured in interleukin 2 and cloned by limiting dilution, and their specificity was determined by direct tests and competitive inhibition assays. C57BL/6 anti-Meth A effector cells recognized H-2Dd determinants. CB6F1 anti-RL male 1 effector cells recognized a unique cell surface antigen of leukemia RL male 1. The specificity was maintained in long-term culture. The cell surface phenotype of the cloned effector cell lines as determined by absorption analysis was Thy-1.2+, Lyt-1.2+, 2.2+, and 3.2+. Cytotoxicity was blocked at the target cell level by antisera against H-2Dd, but not H-2Dk or H-2b, and at the effector cell level by antisera against Lyt-2.2 and 3.2, but not Lyt-1.2, Ly-5.1 or Thy-1.2.