gebhart/patrepeval huggingface dataset:
Paracetamol (Acetaminophen)-Induced Toxicity: Molecular and Biochemical Mechanisms, Analogues and Protective Approaches (2001)

An overview is presented on the molecular aspects of toxicity due to paracetamol (acetaminophen) and structural analogues. The emphasis is on four main topics, that is, bioactivation, detoxication, chemoprevention, and chemoprotection. In addition, some pharmacological and clinical aspects are discussed briefly. A general introduction is presented on the biokinetics, biotransformation, and structural modification of paracetamol. Phase II biotransformation in relation to marked species differences and interorgan transport of metabolites are described in detail, as are bioactivation by cytochrome P450 and peroxidases, two important phase I enzyme families. Hepatotoxicity is described in depth, as it is the most frequent clinical observation after paracetamol-intoxication. In this context, covalent protein binding and oxidative stress are two important initial (Stage I) events highlighted. In addition, the more recently reported nuclear effects are discussed as well as secondary events (Stage II) that spread over the whole liver and may be relevant targets for clinical treatment. The second most frequent clinical observation, renal toxicity, is described with respect to the involvement of prostaglandin synthase, N-deacetylase, cytochrome P450 and glutathione S-transferase. Lastly, mechanism-based developments of chemoprotective agents and progress in the development of structural analogues with an improved therapeutic index are outlined.
Cell-cell interactions in synovitis. Interactions between T lymphocytes and synovial cells. (2000)

Mechanisms whereby T lymphocytes contribute to synovial inflammation in rheumatoid arthritis are poorly understood. Here we review data that indicate an important role for cell contact between synovial T cells, adjacent macrophages and fibroblast-like synoviocytes (FLS). Thus, T cells activated by cytokines, endothelial transmigration, extracellular matrix or by auto-antigens can promote cytokine, particularly TNF alpha, metalloproteinase production by macrophages and FLS through cell-membrane interactions, mediated at least through beta-integrins and membrane cytokines. Since soluble factors thus induced may in turn contribute directly to T cell activation, positive feedback loops are likely to be created. These novel pathways represent exciting potential therapeutic targets.
Altered enteroendocrine cell expression in T cell receptor alpha chain knock-out mice (2000)

Mice lacking T cell receptor alpha chain (TCRalpha(-/-)) develop inflammation of the colon. We have examined the effect of this inflammation on the colonic epithelium by studying markers of epithelial cuff, enteroendocrine, and immune cell differentiation. Using immunohistochemical techniques, colons were compared in normal C57/BL6 and murine TCR alpha(-/-) mice aged 2 and 3 weeks and 3-11 months. TCR alpha(-/-) mice aged 3-11 months had histologic evidence of inflammation with increased expression of CD45, CD4+, CD8+, and B220+ cells and a decrease in expression of IgA+ cells. There was a decrease in the number of cholecystokinin, serotonin, and neurotensin enteroendocrine expressing cells in the colon of TCR alpha(-/-) mice. These changes were not present in 2-3-week-old suckling/weaning mice. In contrast, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1, and gastrin expression did not change and small intestinal enteroendocrine cells remained unaltered. The change in colonic enteroendocrine cell expression appears to be a specific response, since only a subset of these cells was altered, and the epithelium was intact by histologic analysis. The absence of functional T cells in TCR alpha(-/-) colon has a marked effect on differentiation of a specific subpopulation of enteroendocrine cells, prior to loss of integrity of the epithelium.
Strength and Muscle Quality in a Well‐Functioning Cohort of Older Adults: The Health, Aging and Body Composition Study (2003)

In this older cohort, lower strength with older age was predominantly due to a lower muscle mass. Age and body fat also had significant inverse associations with strength and muscle quality. Both preservation of lean mass and prevention of gain in fat may be important in maintaining strength and muscle quality in old age.
Effects of in vivo recombinant methionyl human granulocyte colony- stimulating factor on the neutrophil response and peripheral blood colony-forming cells in healthy young and elderly adult volunteers (1994)

Recombinant granulocyte colony stimulating factor (G-CSF) was administered daily for 14 days to healthy young (Y) (20 to 30 years) and elderly (O) (70 to 80 years) volunteers to evaluate the effects of age on the neutrophil (polymorphonuclear leukocytes, PMN) responses. Thirty-eight volunteers were randomized to receive 0 micrograms, 30 micrograms, or 300 micrograms per day. Baseline neutrophil counts (ANC), peak ANCs, and the rate of attaining the peak ANC were similar in both age groups at both doses. The peak ANC was increased 5-fold at 30 micrograms and 15-fold at 300 micrograms in both the young and elderly. Daily tests of PMN function, as measured by an automated chemiluminescence system, showed nearly identical responses to several agonists for both age groups. Marrow proliferative activity as reflected by the percentage of cells in the marrow neutrophil mitotic pool also increased similarly for both age groups at both doses. In contrast, there was an age-related change in blood colony formation as measured by the blood CFU-GM assay. Compared with controls at the 30 micrograms dose, mean colony formation was increased 2-fold in the young versus no change in the elderly and at the 300 micrograms dose 24-fold in the young versus 12-fold in the elderly. These studies indicate that neutrophil responses to rhG-CSF are equivalent in healthy young and elderly volunteers but the mobilization of progenitor cells, as measured by the CFU-GM assay appears to differ substantially.
Short synthetic oligodeoxyribonucleotide leader sequences enhance accumulation of human proinsulin synthesized in Escherichia coli. (1986)

Enhanced accumulation of human proinsulin synthesized in Escherichia coli has been achieved by inserting a short leader of homooligopeptide at the amino end of proinsulin. Out of 20 amino acid oligomers studied, (Ala)6, (Asn)6, (Cys)7, (Gln)7, (His)6, (Ser)6, and (Thr)6 leaders were the most effective, with the yield of proinsulin ranging between 6% and 26% of the total bacterial protein. These constructions were made by inserting a synthetic oligodeoxyribonucleotide duplex, coding for a small homooligopeptide, between a synthetic proinsulin gene and an eight-codon beta-galactosidase gene residue in vector pUC8. Cyanogen bromide cleavage of the 102 amino acid fused polypeptide yielded a species identical to authentic proinsulin, as judged by NaDodSO4/PAGE and radioimmunoassay.
The Oxidation of Acetals by Ozone (1974)

Ozone reacts very smoothly with acetals to give the corresponding esters. There are six gauche conformations that are theoretically possible for an acetal function. It is shown that only three of them are reactive toward ozone. It is proposed that a reactive acetal function must take a conformation in which each oxygen must have an electron pair orbital oriented antiperiplanar to the C—H bond. The mechanism of this reaction is also discussed.
A Space Tribology Handbook (1997)

The need for a Space Tribology Handbook Tribology (from the Greek ‘tribos’ meaning ‘to rub’) is the study of friction, wear and lubrication. Friction and wear are generated at the interface of contacting bodies in relative motion and therefore occur in components such as bearings, gears, screws and slip-rings. If the friction (or adhesion) forces are high, a component may prove difficult to drive or, even worse, may seize; if high wear occurs, a component will lose its precision and, ultimately, its ability to operate at all. Tribology is, therefore, an important issue, especially in mechanisms intended for use on spacecraft – for if spacecraft mechanisms fail, there is (usually) no means to repair the damage or to apply fresh lubrication. Furthermore, if the mechanism in question is critical to the spacecraft’s operation (as would be the case with solar array drives, antenna pointing mechanisms and deployment devices), then loss of the mission could result. (European Space Tribology Laboratory), which is now part of AEA Technology. Since then, ESTL has generated a considerable amount of tribological data, advised on tribological design issues, and tested tribo-components and mechanisms under space simulated conditions. As a consequence, a wealth of knowledge has been generated and much of this has been disseminated to the space community by way of publications and courses on space tribology. These activities have undoubtedly raised awareness of tribology and encouraged mechanism engineers to give due consideration to tribological issues in their designs. However, there was no handbook available detailing the tribological performance of materials and providing guidelines on their use in mechanisms design. It was for this reason that the Space Tribology Handbook was produced. With its publication, the space community now has a unique document which provides a source of information consolidated by test validation.
Stereochemical Assignment of Intermediates in the Rifamycin Biosynthetic Pathway by Precursor-Directed Biosynthesis (2005)

Natural and semisynthetic rifamycins are clinically important inhibitors of bacterial DNA-dependent RNA polymerase. Although the polyketide-nonribosomal peptide origin of the naphthalene core of rifamycin B is well established, the absolute and relative configuration of both stereocenters introduced by the first polyketide synthase module is obscured by aromatization of the naphthalene ring. To decode the stereochemistry of the rifamycin polyketide precursor, we synthesized all four diastereomers of the biosynthetic substrate for module 2 of the rifamycin synthetase in the form of their N-acetylcysteamine (SNAC) thioester. Only one diastereomer was turned over in vivo into rifamycin B, thus establishing the absolute and relative configuration of the native biosynthetic intermediates.
?Silent? MRI with soft gradient pulses (1999)

A method to reduce the acoustic noise generated by gradient systems in magnetic resonance imaging (MRI) is proposed based on the linear response theory. Since the acoustic frequency response function of typical gradient coils is low in the range below 200 Hz, the noise level can be significantly reduced by using gradient pulse sequences whose spectra are limited to this frequency range. Such "soft," i.e., band-limited, pulse shapes can be designed using sinusoidal ramps individually adjusted to available delays. "Silent" versions of three basic MRI sequences [gradient-echo (GE), spin-echo (SE), and rapid acquisition with relaxation enhancement (RARE)] were programmed on 2 and 3 T whole-body scanners. High-quality images could be acquired at noise levels as low as 40 dBA (GE and SE) and 60 dBA (RARE).
Human β‐mannosidase deficiency associated with peripheral neuropathy (1994)

Human beta-mannosidosis is an inherited lysosomal storage disorder described in only seven families. We present a further case in a black African 14-year-old boy with severely deficient beta-mannosidase activity, bilateral thenar and hypothenar amyotrophy, electrophysiologically demonstrable demyelinating peripheral neuropathy, and cytoplasmic vacuolation of skin fibroblasts and lymphoid cells. The clinical and biochemical features of our patient are compared to those of previously reported patients.
Colorectal carcinogenesis is associated with stromal expression of COL11A1 and COL5A2 (2001)

Collagen is the major component of the interstitial extracellular matrix (ECM). ECM is known to play an active role in numerous biological processes such as cell shape, proliferation, migration, differentiation, apoptosis as well as carcinogenesis. We used mRNA differential display RT-PCR to study differentially expressed genes in tissue samples from 24 colorectal cancers and four normal colon epithelia. Twenty of the 24 tumours showed expression of a gene COL11A1, not expressed in the normal samples. This gene is not normally expressed in adult colon tissue, but was here found to be expressed in 27 out of a total of 34 (79%) colorectal carcinomas. An analysis of other collagens showed that COL5A2 was not expressed in normal colon but was co-expressed with COL11A1 in the tumours. Our results suggest that stromal expression of COL11A1 and COL5A2 is associated with malignancy in colorectal cancer.
A Java-based information browsing system in a remote display environment (2004)

In this paper, we describe our design and implementation of an information browsing system using Java-based cellular phones in a remote display environment which we have proposed. In this system, an application on a remote display displays various information for users, and a Java application on a cellular phone displays operational pages for users to operate the application on the remote display. Users can operate the application and browse information on the remote display by operating the corresponding operational pages on the cellular phone.
CA125 in Ovarian Cancer (2007)

A quarter of a century since its discovery, circulating CA125 antigen is recommended for clinical use in the USA for ovarian cancer screening of high-risk women with ovaries, despite its limited sensitivity and specificity. Recent findings suggest that CA125 might also serve as a predictive marker for pre-invasive ovarian carcinoma. Methods to quantify circulating CA125 evolved toward sensitive and reliable double-determinant ELISA assays. The CA125 gene, MUC16, was cloned 20 years after the protein discovery and revealed a very complex and unusual glycoprotein structure, suggesting an immunological role. Recent evidence points toward CA125 function in the induction of materno-fetal tolerance through the alteration of natural killer phenotype. Two receptors for CA125 have been described: mesothelin and galectin-1. The specific location and functional proprieties of CA125 make it a therapeutic target of choice; clinical trials have demonstrated that anti-CA125 injections are well tolerated and suggest a potential survival benefit.
The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces (2005)

Secretory antibodies of the immunoglobulin A (IgA) class form the first line of antigen-specific immune protection against inhaled, ingested, and sexually transmitted pathogens and antigens at mucosal surfaces. Epithelial transcytosis of polymeric IgA (pIgA) is mediated by the polymeric immunoglobulin receptor (pIgR). At the apical surface, the extracellular ligand-binding region of pIgR, known as secretory component (SC), is cleaved and released in free form or as a component of secretory IgA (SIgA). SC has innate anti-microbial properties, and it protects SIgA from proteolytic degradation. Expression of pIgR is regulated by microbial products through Toll-like receptor signaling and by host factors such as cytokines and hormones. Recent studies of the structure of the extracellular ligand-binding domain of pIgR have revealed mechanisms by which it binds pIgA and other ligands. During transcytosis, pIgA has been shown to neutralize pathogens and antigens within intracellular vesicular compartments. The recent identification of disease-associated polymorphisms in human pIgR near the cleavage site may help to unravel the mystery of how pIgR is cleaved to SC. The identification of novel functions for SC and SIgA has expanded our view of the immunobiology of pIgR, a key component of the mucosal immune system that bridges innate and adaptive immune defense.
Reversible in situ acid formation for β-pinene hydrolysis using CO2expanded liquid and hot water (2004)

Large amounts of waste may result from the neutralization of homogeneous acid catalysts following reaction. Here we present examples of in situ acid formation and self-neutralization, thus eliminating waste and offering advantages for product recovery. The formation of α-terpineol (2) from β-pinene (1) is a reaction of commercial significance that is typically run with strong acid. We demonstrate that the reaction can be performed under more environmentally benign conditions using the in situ acid formation capabilities of two different green technologies: CO2 expanded liquids and reactions in hot water (200 °C). This work presents an example of the application of these methods to a reaction that has commercial significance and adds to our knowledge about the benefits and effects of co-solvents. The relative rates and product distributions achieved in each system are presented and discussed.
ZAP-70 and SLP-76 Regulate Protein Kinase C-θ and NF-κB Activation in Response to Engagement of CD3 and CD28 (2001)

The transcription factor NF-kappaB is a critical regulator of T cell function that becomes strongly activated in response to coengagement of TCR and CD28. Although events immediately proximal to NF-kappaB activation are well understood, uncertainty remains over which upstream signaling pathways engaged by TCR and CD28 lead to NF-kappaB activation. By using Jurkat T cell lines that are deficient or replete for either the protein tyrosine kinase ZAP-70 or the cytosolic adapter molecule SLP-76, the role of these proteins in modulating NF-kappaB activation was examined. NF-kappaB was not activated in response to coengagement of TCR and CD28 in either the ZAP-70- or SLP-76-negative cells, whereas stimuli that bypass these receptors (PMA plus A23187, or TNF-alpha) activated NF-kappaB normally. Protein kinase C (PKC) theta activation, which is required for NF-kappaB activation, also was defective in these cells. Reexpression of ZAP-70 restored PKCtheta and NF-kappaB activation in response to TCR and CD28 coengagement. p95(vav) (Vav)-1 tyrosine phosphorylation was largely unperturbed in the ZAP-70-negative cells; however, receptor-stimulated SLP-76/Vav-1 coassociation was greatly reduced. Wild-type SLP-76 fully restored PKCtheta and NF-kappaB activation in the SLP-76-negative cells, whereas 3YF-SLP-76, which lacks the sites of tyrosine phosphorylation required for Vav-1 binding, only partially rescued signaling. These data illustrate the importance of the ZAP-70/SLP-76 signaling pathway in CD3/CD28-stimulated activation of PKC theta and NF-kappaB, and suggest that Vav-1 association with SLP-76 may be important in this pathway.
Acute Nicotine Administration in Alzheimer’s Disease: An Exploratory EEG Study (2000)

Previous findings of cognitive deficits and EEG slowing in Alzheimer's patients, together with independent reports of the performance enhancing and electrocortical activating properties of nicotine in normal adults, stimulated this study to examine the acute effects of nicotine on spectrum-analyzed EEG in patients with dementia of the Alzheimer type (DAT). Thirteen patients, 6 currently receiving cholinesterase inhibitor treatment and the remaining being medication free, were administered 2 mg of nicotine polacrilex under randomized, placebo-controlled conditions. Compared to age-regressed EEG norms, the pretreatment EEG spectrums of patients in general were characterized by excessive slow (delta and theta)-wave power, diminished fast (alpha and beta)-wave power and slow mean alpha and total band frequencies. Although postnicotine EEG indices remained within the abnormal range, nicotine, compared to placebo, significantly shifted EEG towards normal values by reducing slow wave (relative delta and theta) power and augmenting fast (relative alpha-1, alpha-2, beta-1) wave power. No differences were observed between treated and nontreated patients in response to nicotine. The results are discussed in relation to cholinergic and brain arousal systems and their relationship to cognitive processes.
MicroRNA Expression Analysis in Multiple Myeloma Plasma Cells and Cell Lines by a Quantitative Real-Time PCR Approach. (2007)

Abstract MicroRNAs (miRNAs) are small RNA molecules that negatively regulate gene expression at the post transcriptional level. Over the past few years, these miRNAs have been shown to be widely involved in diverse biological processes, like apoptosis, cell metabolism and cancer. The aim of this study was to compare the miRNA expression in multiple myeloma plasma cells to that in their normal counterparts. A subset of ten miRNAs was chosen based upon evidence in the literature for their role in tumorigenesis with special emphasis on B cell malignancies. The expression of mature miRNAs was examined with quantitative real-time reverse transcription based polymerase chain reaction (TaqMan®MicroRNA assay) in 7 human multiple myeloma (MM) cell lines, in purified bone marrow derived plasma cells from 4 MM patients, one MGUS patient and 3 healthy adults. The plasma cells from patients and controls were positively selected using CD138-coated microbeads. Our results showed that miR-15a and miR-21 were equally expressed in cell lines, patients and healthy controls. Therefore, these 2 miRNAs were used for normalization. All data were compared with the data derived from normal plasma cells. Higher expression was seen for let-7a, miR-16 and 2 members of the miR-17 cluster (miR-17-5p and miR-19b) both in MM patients and cell lines. Expression of miR-16 was much higher in the MM plasma cells than in the MGUS plasma cells (only one sample). The miR-181a showed a heterogeneous expression in cell lines but was normally expressed in patients. The miR-372 expression was below the level of accurate quantification in all samples. There was a dramatic difference between the stroma dependent (MM5.1) and the stroma independent cell line (MM5.2) in miR-155 expression. The miR-143 was less abundant in all cell lines and in one MM sample that contained more than 90% plasma cells. Interestingly, the MM5.2 cell line, which is stroma independent, reflecting a more aggressive MM stage, showed also a much lower expression for miR-143 than the stroma dependent counterpart (MM5.1). In summary, the results of this study show that there is a difference in miRNA expression between MM plasma cells and their healthy counterparts and also between more and less aggressive MM plasma cells, suggesting that miRNAs could play a role in disease onset and progression.