gebhart/patrepeval huggingface dataset:
Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. (1985)

Repeated immunization of normal C57L/J (H-2b) mice with peripheral T cells from BALB.B (H-2b) mice results in the production of antibodies which react with the T cell receptor. A monoclonal antibody-producing hybridoma, F23.1, was isolated from immunized C57L/J mice showing this property. This monoclonal antibody recognizes approximately 25% of peripheral T cells in BALB mice. It stains approximately the same fraction of T cells and precipitates the same heterodimer as the rat monoclonal antibody described previously that was made against isolated receptor material. The allotypic determinant recognized by this monoclonal antibody is present in most common laboratory strains (BALB, C57BL, CBA, A, DBA, C3H) and is absent in C57L, C57BR, and SJL mice. Sorting peripheral T cells from BALB.B or (SJL X BALB/c)F1 mice for the F23.1+ and F23.1- subsets revealed that both populations contain approximately the same CTL precursor frequency for alloantigen. Thus, the T cell receptor allotype defined by F23.1 is present on CTL. Furthermore, cytotoxicity mediated by an F23.1+ CTL line could be blocked specifically by the F23.1 monoclonal antibody. Under appropriate conditions, the monoclonal antibody F23.1 bound to Sepharose 4B beads can induce resting peripheral T lymphocytes of allotype-positive strains to proliferate.
Metagenomics: Key to Human Gut Microbiota (2011)

The human gastrointestinal tract harbors the most complex human microbial ecosystem (intestinal microbiota). The comprehensive genome of these microbial populations (intestinal microbiome) is estimated to have a far greater genetic potential than the human genome itself. Correlations between changes in composition and activity of the gut microbiota and common disorders, such as inflammatory bowel diseases, obesity, diabetes, and atopic diseases, have been proposed, increasing the interest of the scientific community in this research field. In this perspective, a comprehensive and detailed view of the human gut microbiota, in terms of phylogenetic composition as well as genetic and metabolic potential, is essential to understand the dynamics and possible mechanisms of the cause/effect relationships between gut microbiota and pathology. Metagenomics has emerged as one of the most powerful sequence-driven approaches to study the composition and the genetic potential of this complex ecosystem, and efforts in this direction have been smoothed by the implementation of next generation sequencing platforms. Here, we highlight the potential of the newest high-throughput, culture-independent approaches for the characterization of the human gut microbiome in health and disease. Recent and promising results in this field are presented, underlining the perspectives and future research direction of human gut microbial ecology.
Cell-surface heparan sulfate proteoglycans: dynamic molecules mediating ligand catabolism (1997)

Though sometimes regarded as merely passive, space-filling components, proteoglycans are in fact metabolically active molecules with carbohydrate and protein domains that are highly conserved throughout evolution, indicating specific, crucial functions. Here we review recent evidence that heparan sulfate proteoglycans, particularly syndecans and perlecan, are able to mediate directly the internalization of lipoproteins and other ligands, without requiring the participation of LDL receptor family members. Thus, heparan sulfate proteoglycans can function as receptors. In the case of syndecan heparan sulfate proteoglycans, efficient internalization is triggered by clustering of the transmembrane and cytoplasmic domains and then proceeds through a noncoated pit pathway, possibly caveolae. The physiologic and pathophysiologic importance of these direct heparan sulfate proteoglycan-mediated catabolic pathways in the liver and in the arterial wall in vivo remains to be settled.
Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source (2019)

Substitution of Primex with palm oil promotes a similar phenotype of biopsy-confirmed NASH in <i>ob/ob</i> and C57BL/6J mice, making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.
Biochemistry of azacitidine: a review. (1987)

Azacitidine is a pyrimidine ring analog of cytidine that is incorporated into RNA causing alteration in RNA synthesis and processing and resulting in inhibition of protein synthesis. Azacitidine as the deoxynucleotide is also incorporated into DNA inhibiting its synthesis and blocking cytosine methylation by noncompetitive inhibition of DNA methyltransferase. The resulting hypomethylation of DNA is thought to induce gene activation and expression and cell differentiation. This may be an underlying factor in azacitidine's antileukemic activity and also contributes to its carcinogenic and tumor-promoting properties in experimental models.
Vascular Endothelial Growth Factor Has Neurotrophic Activity and Stimulates Axonal Outgrowth, Enhancing Cell Survival and Schwann Cell Proliferation in the Peripheral Nervous System (1999)

Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells, and it promotes angiogenesis in vivo. Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth. Maximal effect was observed at 10-50 ng/ml for SCG and 100 ng/ml for DRG. VEGF-induced axonal outgrowth was inhibited by the mitogen-activated protein kinase kinase inhibitor PD 98059 but not by the protein kinase inhibitor K252a. VEGF also increased survival of both neurons and satellite cells and the number of proliferating Schwann cells. Immunocytochemistry and immunoblotting revealed that VEGF was expressed in virtually all nerve cells in the SCG but only in a population of small-diameter (<35 micrometers) neurons representing approximately 30% of the neurons in DRG. Immunostaining showed that the VEGF receptor fetal liver kinase receptor (flk-1) was found on nerve cell bodies in DRG and to a lesser extent on neurons in SCG. Growth cones of regenerating axons from both types of ganglia exhibited flk-1 immunoreactivity, as did Schwann cells. We conclude that VEGF has both neurotrophic and mitogenic activity on cells in the peripheral nervous system.
Development and Evaluation of Functional Gene Arrays for Detection of Selected Genes in the Environment (2001)

To determine the potential of DNA array technology for assessing functional gene diversity and distribution, a prototype microarray was constructed with genes involved in nitrogen cycling: nitrite reductase (nirS and nirK) genes, ammonia mono-oxygenase (amoA) genes, and methane mono-oxygenase (pmoA) genes from pure cultures and those cloned from marine sediments. In experiments using glass slide microarrays, genes possessing less than 80 to 85% sequence identity were differentiated under hybridization conditions of high stringency (65 degrees C). The detection limit for nirS genes was approximately 1 ng of pure genomic DNA and 25 ng of soil community DNA using our optimized protocol. A linear quantitative relationship (r(2) = 0.89 to 0.94) was observed between signal intensity and target DNA concentration over a range of 1 to 100 ng for genomic DNA (or genomic DNA equivalent) from both pure cultures and mixed communities. However, the quantitative capacity of microarrays for measuring the relative abundance of targeted genes in complex environmental samples is less clear due to divergent target sequences. Sequence divergence and probe length affected hybridization signal intensity within a certain range of sequence identity and size, respectively. This prototype functional gene array did reveal differences in the apparent distribution of nir and amoA and pmoA gene families in sediment and soil samples. Our results indicate that glass-based microarray hybridization has potential as a tool for revealing functional gene composition in natural microbial communities; however, more work is needed to improve sensitivity and quantitation and to understand the associated issue of specificity.
Diagnosis, Evaluation and Follow-Up of Asymptomatic Microhematuria (AMH) in Adults: AUA Guideline (2012)

AMH is only diagnosed by microscopy; a dipstick reading suggestive of hematuria should not lead to imaging or further investigation without confirmation of three or greater red blood cells per high power field. The evaluation and follow-up algorithm and guidelines provide a systematic approach to the patient with AMH. All patients 35 years or older should undergo cystoscopy, and upper urinary tract imaging is indicated in all adults with AMH in the absence of known benign causation. The imaging modalities and physical evaluation techniques are evolving, and these guidelines will need to be updated as the effectiveness of these become available. Please visit the AUA website at http://www.auanet.org/content/media/asymptomatic_microhematuria_guideline.pdf to view this guideline in its entirety.
On-Chip Process Variation Detection and Compensation Using Delay and Slew-Rate Monitoring Circuits (2008)

In the nm design era, post-fabrication process characterization and compensation have become extremely important for mitigating the impact of process variations on the parametric yield. In this paper, a new variation detection and compensation scheme is presented that uses both slew and delay metrics to gauge the drive-strengths of and mismatch of NMOS and PMOS devices. The importance of considering both of these metrics is illustrated. Four compensation schemes are analyzed, based on delay or slew as the detection metric, with the ability to apply forward and reverse body-biasing. Design considerations, simulation results and power-performance characteristics of these schemes in a 45 nm SOI technology are presented. These schemes are shown to be capable of adjusting the critical path delay of the die to within the desired plusmn3% of the nominal delay while reducing the total power dissipation by an average of ~8% across various process corners.
Molecular Recognition of a Three‐Way DNA Junction by a Metallosupramolecular Helicate (2006)

Three point turn: A metallosupramolecular helicate with trigonal-antiprismatic geometry fits perfectly into the central hydrophobic cavity of a three-way DNA junction allowing a new mode of DNA recognition.
A Novel Three-Pronged Approach to Kill Cancer Cells Selectively: Concomitant Viral, Double Suicide Gene, and Radiotherapy (1998)

Two obstacles limiting the efficacy of nearly all cancer gene therapy trials are low gene transduction efficiencies and the lack of tumor specificity. Recently, a replication-competent, E1B-attenuated adenovirus (ONYX-015) was developed that could overcome these limitations, because it was capable of efficiently and selectively destroying tumor cells lacking functional p53. In an attempt to improve both the efficacy and safety of this approach, we constructed a similar adenovirus (FGR) containing a cytosine deaminase (CD)/herpes simplex virus type-1 thymidine kinase (HSV-1 TK) fusion gene, thereby allowing for the utilization of double-suicide gene therapy, which has previously been demonstrated to produce significant antitumor effects and potentiate the therapeutic effects of radiation. The FGR virus exhibited the same tumor cell specificity and replication kinetics as the ONYX-015 virus in vitro. Importantly, both the CD/5-FC and HSV-1 TK/GCV suicide gene systems markedly enhanced the tumor cell-specific cytopathic effect of the virus, and, as expected, sensitized tumor cells to radiation. By contrast, neither the FGR virus nor either suicide gene system showed significant toxicity to normal human cells. Both suicide gene systems could be used to suppress viral replication effectively, thereby providing a means to control viral spread. The results support the thesis that the three-pronged approach of viral therapy, suicide gene therapy, and radiotherapy may represent a powerful and safe means of selectively destroying tumor cells in vivo.
DNA sequence specificity of doxorubicin-induced mutational damage in uvrB- Escherichia coli. (1991)

In the absence of excision repair, doxorubicin caused a striking (41-fold) increase in the frequency of large deletion mutations extending from the lac operator (lacO) into the lac repressor gene (lacI) of Escherichia coli. In contrast, there was only a 2-fold increase in the frequency of small deletions despite a 3-fold increase in overall mutation frequency. The 5'-endpoints of doxorubicin-induced lacO and lacI/lacO deletions occurred at the DNA sequence 5'-pyTAA or 5'-AATpy (where py is pyrmidine) (16%), at runs of purines or pyrimidines (41%) and adjacent to 5'-dGdC or 5'-dCdG doublets (34%). Ninety % (27 of 30) of the doxorubicin-induced deletions involving the region of the lacO palindrome had 3'-endpoints within the palindrome sequence as compared with 40% (4 of 10) spontaneous deletions in an untreated set. Doxorubicin-induced single base substitutions were highly focused at one site (4 of 6) in the i-d region of lacI, in contrast to the spontaneous distribution of point mutations, where 16 mutants were recovered at 12 different sites. An increased frequency (3-fold) of highly focused base substitutions was also observed at 2 sites in the lac operator region (at lacO +6, which is a transition "hotspot" in the spontaneous spectra of both wild type and uvrB- organisms and at the adjacent +5 site). Notably, the frequency of 1- and 2-base frameshifts did not increase in the doxorubicin-induced spectrum, relative to the spontaneous mutation spectrum. These in vivo observations in E. coli suggest that in the absence of excision repair, doxorubicin causes highly focused deletions and base substitutions. These mutations occur adjacent to DNA sequences identified in previous in vitro studies as preferential sites of doxorubicin binding.
Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium‐dependent potassium channel opening (2009)

Probiotics are live non-pathogenic commensal organisms that exert therapeutic effects in travellers' diarrhea, irritable bowel syndrome and inflammatory bowel disease. Little is known about mechanisms of action of commensal bacteria on intestinal motility and motility-induced pain. It has been proposed that probiotics affect intestinal nerve function, but direct evidence for this has thus far been lacking. We hypothesized that probiotic effects might be mediated by actions on colonic intrinsic sensory neurons. We first determined whether sensory neurons were present in rat colon by their responses to chemical mucosal stimulation and identified them in terms of physiological phenotype and soma morphotype. Enteric neuron excitability and ion channel activity were measured using patch clamp recordings. We fed 10(9)Lactobacillus reuteri (LR) or vehicle control to rats for 9 days. LR ingestion increased excitability (threshold for evoking action potentials) and number of action potentials per depolarizing pulse, decreased calcium-dependent potassium channel (IK(Ca)) opening and decreased the slow afterhyperpolarization (sAHP) in sensory AH neurons, similar to the IK(Ca) antagonists Tram-34 and clotrimazole. LR did not affect threshold for action potential generation in S neurons. Our results demonstrate that LR targets an ion channel in enteric sensory nerves through which LR may affect gut motility and pain perception.
Experimental vaccination against group B streptococcus, an encapsulated bacterium, with highly purified preparations of cell surface proteins Rib and alpha (1996)

Encapsulated bacteria cause some of the most common diseases in humans. Although the polysaccharide capsules of these pathogens have attracted the most attention with regard to vaccine development, recent evidence suggests that bacterial surface proteins may also be used to confer protective immunity. We have analyzed this possibility in group B streptococcus (GBS), an encapsulated bacterium that is the major cause of invasive bacterial disease in the neonatal period. Previous work has shown that the majority of GBS strains causing invasive infections express the Rib protein, and that most strains lacking Rib express a protein designated alpha. Here we report that active immunization with highly purified preparations of Rib or alpha protected mice against lethal infection with strains expressing the corresponding protein. Vaccination with the Rib protein protected against two strains of capsular type III and two strains of type II, and vaccination with the alpha protein protected against one strain of type II and one strain of type Ib. The mice vaccinated with Rib or alpha showed a good immunoglobulin G response to the immunogen. These data suggest that a vaccine against GBS disease may be based on cell surface proteins and support the notion that proteins may be used for immunization against encapsulated bacteria.
Hepatic growth induced by injection of the liver growth factor into normal rats. (1994)

Normal Wistar rats injected with the liver growth factor (LGF), a mitogen specific for liver cells, experienced hepatic growth. LGF shows two peaks of activity in vivo, both of them mitogenic. Rats injected either with 6.8 ng or 3.9 micrograms LGF/rat every 3-4 days experienced liver growth showing a see-saw profile. Dry liver weight usually peaked at day 2 (microgram doses) or at day 3 (ng doses) after each injection, with increases of about 30% over controls. Liver DNA synthesis, measured by [3H]-thymidine incorporation, peaked 24 h after LGF injection at both doses. Liver protein synthesis, measured by [14]C-leucine incorporation, usually peaked 24 h after DNA synthesis maximums. Mitogen-stimulated cells were also assessed by immunohistochemical staining for proliferating cell nuclear antigen in livers of LGF-injected rats. Rats injected with rat serum albumin purified from normal rats to serve as controls showed a 6% increase in dry liver weight, but when serum albumin from 3-day fasted rats was injected instead, the increase was not statistically significant. The mild effect of rat serum albumin could be due to the lipid content of the solutions injected, but the level of lipids/mg protein in LGF solutions was half that determined with serum albumin from 3-day fasted rats. From the microscopic and ultramicroscopic studies carried out in rat livers injected with LGF at each dose, we observed: (1) an increase in the number of hepatocytes undergoing mitosis; (2) transient increases in lipid and glycogen contents, as occur after liver resection; (3) no signs of degeneration, such as the appearance of amyloids or fibrosis; (4) no increase in lysosome number, as in hepatotoxicity; (5) no alterations in endothelial or Kupffer cells; and (6) no ultrastructural signs of degeneration either in cytoplasmic organelles (rough endoplasmic reticulum, mitochondria) or in nuclei. One year after LGF injection, rat liver, pancreas, kidneys and spleen were normal, with no signs of degeneration or onset of fibrosis.
The effect of splanchnic nerve stimulation on adrenocortical activity in conscious calves. (1987)

1. Right adrenal and various cardiovascular responses to stimulation of the peripheral end of the right splanchnic nerve have been investigated in the presence and absence of exogenous adrenocorticotrophin, ACTH1-24, (5 ng min-1 kg-1). The adrenal-clamp technique was employed in conscious calves in which the pituitary stalk had been cauterized 3-4 days previously. 2. The I.V. infusion of ACTH1-24 increased mean plasma ACTH concentration by about 1200 pg/ml and mean right adrenal cortisol output by about 500 ng min-1 kg-1. Stimulation of the peripheral end of the right splanchnic nerve at 4 Hz for 10 min produced a further rise in cortisol output, amounting to about 400 ng min-1 kg-1 (P less than 0.01). These changes in output were reflected accurately by changes in peripheral plasma cortisol concentration. 3. Closely similar amounts of adrenaline were released in response to splanchnic nerve stimulation in the presence and absence of exogenous ACTH. In the presence of ACTH the average mean output of noradrenaline (58 +/- 2 ng min-1 kg-1) was significantly less than that of adrenaline (102 +/- 4 ng min-1 kg-1; P less than 0.001), whereas the corresponding values were not significantly different in the absence of ACTH. 4. These results also confirm the fact that the fall in adrenal vascular resistance which occurs during splanchnic nerve stimulation is substantially reduced by ACTH, as is the rise in met5-enkephalin output. 5. It is concluded that the splanchnic innervation is capable of enhancing the secretion of adrenal glucocorticoids in response to ACTH under physiological conditions in the conscious calf.
The role of metacaspase 1 in Plasmodium berghei development and apoptosis (2007)

The malaria parasite encodes a wide range of proteases necessary to facilitate its many developmental transitions in vertebrate and insect hosts. Amongst these is a predicted cysteine protease structurally related to caspases, named Plasmodium metacaspase 1 (PxMC1). We have generated Plasmodium berghei parasites in which the PbMC1coding sequence is removed and replaced with a green fluorescent reporter gene to investigate the expression of PbMC1, its contribution to parasite development, and its involvement in previously reported apoptosis-like cell death of P. berghei ookinetes. Our results show that the pbmc1 gene is expressed in female gametocytes and all downstream mosquito stages including sporozoites, but not in asexual blood stages. We failed to detect an apparent loss-of-function phenotype, suggesting that PbMC1 constitutes a functionally redundant gene. We discuss these findings in the context of two other putative Plasmodium metacaspases that we describe here.
Agonists and Antagonists Acting at P2X7 Receptor (2004)

The P2X(7) receptor is involved in several processes relevant to inflammation (cytokine release, NO generation, killing of intracellular pathogens, cytotoxicity), thus, it may be an appealing target for pharmacological intervention. The characterisation of native and recombinant P2X(7) receptor continues to be hindered by the lack of specific and subtype-selective agonists and antagonists. BzATP is currently the most potent agonist known at the endogenous and recombinant P2X(7) receptor A tyrosine derivative named KN-62 exhibits selective P2X(7) receptor-blocking properties. In this review article we have reported novel series of KN-62-related compounds of the general structure R(1)-Tyr(OR(2))-piperazinyl-R(3), in which three positions (R(1), R(2) and R(3)) were systematically varied. Two recent articles published by AstraZeneca have reported that novel series of cyclic imides and adamantane amides are potent P2X(7) receptor antagonists.
Multicache-based content management for Web caching (2002)

Large-scale Web caches are, in fact, localized sources of Web contents. Besides replacement policies, which decide the contents of a cache, the management of such contents is an issue of special significance to Web caching. This paper introduces our ongoing work on the research of cache content management. We propose a multi-cache-based content management scheme in which Web contents are distributed to several subcaches rather than maintained in a monolithic priority queue. This scheme is suitable for managing a large cache space and is capable of implementing sophisticated control logic. The efficiency of this scheme is demonstrated by the design and implementation of a new replacement policy. Trace-driven simulations are used to evaluate these results.