gebhart/patrepeval huggingface dataset:
Death of the Escherichia coli K-12 strain W3110 in soil and water (1996)

Whether Escherichia coli K-12 strain W3110 can enter the "viable but nonculturable" state was studied with sterile and nonsterile water and soil at various temperatures. In nonsterile river water, the plate counts of added E. coli cells dropped to less than 10 CFU/ml in less than 10 days. Acridine orange direct counts, direct viable counts, most-probable-number estimates, and PCR analyses indicated that the added E. coli cells were disappearing from the water in parallel with the number of CFU. Similar results were obtained with nonsterile soil, although the decline of the added E. coli was slower. In sterile water or soil, the added E. coli persisted for much longer, often without any decline in the plate counts even after 50 days. In sterile river water at 37 degrees C and sterile artificial seawater at 20 and 37 degrees C, the plate counts declined by 3 to 5 orders of magnitude, while the acridine orange direct counts remained unchanged. However, direct viable counts and various resuscitation studies all indicated that the nonculturable cells were nonviable. Thus, in either sterile or nonsterile water and soil, the decline in plate counts of E. coli K-12 strain W3110 is not due to the cells entering the viable but nonculturable state, but is simply due to their death.
Translational Mini-Review Series on B Cell-Directed Therapies: Recent advances in B cell-directed biological therapies for autoimmune disorders (2009)

B cell-directed therapies are promising treatments for autoimmune disorders. Besides targeting CD20, newer B cell-directed therapies are in development that target other B cell surface molecules and differentiation factors. An increasing number of B cell-directed therapies are in development for the treatment of autoimmune disorders. Like rituximab, which is approved as a treatment for rheumatoid arthritis (RA), many of these newer agents deplete B cells or target pathways essential for B cell development and function; however, many questions remain about their optimal use in the clinic and about the role of B cells in disease pathogenesis. Other therapies besides rituximab that target CD20 are the furthest along in development. Besides targeting CD20, the newer B cell-directed therapies target CD22, CD19, CD40-CD40L, B cell activating factor belonging to the TNF family (BAFF) and A proliferation-inducing ligand (APRIL). Rituximab is being tested in an ever-increasing number of autoimmune disorders and clinical studies of rituximab combined with other biological therapies are being pursued for the treatment of rheumatoid arthritis (RA). B cell-directed therapies are being tested in clinical trials for a variety of autoimmune disorders including RA, systemic lupus erythematosus (SLE), Sjögren's syndrome, vasculitis, multiple sclerosis (MS), Graves' disease, idiopathic thrombocytopenia (ITP), the inflammatory myopathies (dermatomyositis and polymyositis) and the blistering skin diseases pemphigus and bullous pemphigoid. Despite the plethora of clinical studies related to B cell-directed therapies and wealth of new information from these trials, much still remains to be discovered about the pathophysiological role of B cells in autoimmune disorders.
Endocannabinoids and cannabinoid receptors in ischaemia–reperfusion injury and preconditioning (2007)

Ischaemia-reperfusion (I/R) is a pivotal mechanism of organ injury during stroke, myocardial infarction, organ transplantation and vascular surgeries. Ischaemic preconditioning (IPC) is a potent endogenous form of tissue protection against I/R injury. On the one hand, endocannabinoids have been implicated in the protective effects of IPC through cannabinoid CB1/CB2 receptor-dependent and -independent mechanisms. However, there is evidence suggesting that endocannabinoids are overproduced during various forms of I/R, such as myocardial infarction or whole body I/R associated with circulatory shock, and may contribute to the cardiovascular depressive state associated with these pathologies. Previous studies using synthetic CB1 receptor agonists or knockout mice demonstrated CB1 receptor-dependent protection against cerebral I/R injury in various animal models. In contrast, several follow-up reports have shown protection afforded by CB1 receptor antagonists, but not agonists. Excitedly, emerging studies using potent CB2 receptor agonists and/or knockout mice have provided compelling evidence that CB2 receptor activation is protective against myocardial, cerebral and hepatic I/R injuries by decreasing the endothelial cell activation/inflammatory response (for example, expression of adhesion molecules, secretion of chemokines, and so on), and by attenuating the leukocyte chemotaxis, rolling, adhesion to endothelium, activation and transendothelial migration, and interrelated oxidative/nitrosative damage. This review is aimed to discuss the role of endocannabinoids and CB receptors in various forms of I/R injury (myocardial, cerebral, hepatic and circulatory shock) and preconditioning, and to delineate the evidence supporting the therapeutic utility of selective CB2 receptor agonists, which are devoid of psychoactive effects, as a promising new approach to limit I/R-induced tissue damage.
Rapid injury to peas by soil waterlogging (1979)

Abstract Short‐term responses of pea plants ( Pisum sativum L. cv. ‘Sprite’) to waterlogging of the soil have been examined under glasshouse conditions. The symptoms of injury arising from one to four days of waterlogging included extensive desiccation and chlorosis of the foliage and lower rates of transpiration, stem extension, and growth of shoots and fruits. Premature quiescence of the apical bud of waterlogged plants reduced the number of fruiting nodes and extending internodes. Flowering plants at the 9‐ to 10‐leaf stage were found to be damaged more severely than young veetative plants bearing only 2 or 3 leaves. Waterlogging inhibited the uptake of nitrogen from the soil sufficiently to reduce its concentration in vegetative and fruit tissues. The uptake of potassium and phosphorus was less severely affected and the overall concentration in shoot tissues was slightly higher in waterlogged plants than in controls. The concentrations of manganese and calcium were not changed greatly by waterlogging. The equilibrium concentration of oxygen in the soil water fell to below 1% after 24 h of waterlogging while the amounts of carbon dioxide, nitrous oxide and ethylene increased considerably. The injury to plants grown in nutrient solution supplied with oxygen and carbon dioxide, at concentrations present in waterlogged soil, was much less than that sustained by plants growing in the waterlogged soil itself.
Heteroepitaxy of high-quality Ge on Si by nanoscale seed pads grown through a SiO 2 interlayer (2005)

Growing a lattice-mismatched, dislocation-free epitaxial film on Si has been a challenge for many years. Herein, we exploit nanoscale heterojunction engineering to grow high-quality Ge epilayer on Si. A 1.2-nm-thick chemical SiO<sub>2</sub> film is produced on Si in a H<sub>2</sub>O<sub>2</sub> and H<sub>2</sub>SO<sub>4</sub> solution. When the chemically oxidized Si substrate is exposed to Ge molecular beam, relatively uniform-size nanoscale seed pads form in the oxide layer and "touchdown" on the underlying Si substrate. Although the touchdown location is random, the seed pad growth is self-limiting to 7 nm in size. Upon continued exposure, Ge selectively grows on the seed pads rather than on SiO<sub>2</sub>, and the seeds coalesce to form an epilayer. The Ge epilayer is characterized by high-resolution, cross-sectional as well as plan-view transmission electron microscopy, Raman spectroscopy, and etch-pit density (EPD). The cross-sectional TEM images reveal that the Ge epilayer is free of dislocation network and that the epilayer is fully relaxed at 2 nm from the heterojunction. The Raman shift of Ge optical phonon mode exactly matches that of relaxed bulk Ge, further supporting that the epilayer is fully relaxed. The cross-sectional TEM images, however, show that stacking faults exist near the Ge-SiO<sub>2</sub> interface. A small fraction (~4x10<sup>-3</sup>%) of these stacking faults propagate to the epilayer surface. The plan-view TEM sampling provides an estimate on the density of stacking faults (SF) at approximately 10<sup>6</sup> cm<sup>-2</sup> and threading dislocations (TD) far below 10<sup>6</sup> cm<sup>-2</sup>. The SF and TD propagating to the surface form etch pits, when immersed in a solution containing HF, HNO<sub>3</sub>, glacial acetic acid, and I<sub>2</sub>. The total EPD, as a statistically more reliable estimate on SF and TD than the plan-view TEM, is consistently less than 2x10<sup>6</sup> cm<sup>-2</sup>, where SFs constitute 99 %, and TDs constitute 1 %. That is, the TD density is ~10<sup>5</sup> cm<sup>-2</sup> as a conservative upper bound. The reduction of strain density near the Ge-Si heterojunction, leading to high quality Ge epilayer, is attributed to (1) a high density (~10<sup>11</sup> cm<sup>-2</sup>) of nanoscale Ge seed pads interspaced by 2- to 12-nm-wide SiO<sub>2</sub> patches and (2) the SiO<sub>2</sub> patches serving as artificially introduced dislocation centers. Burgers circuit around each SiO<sub>2</sub> patch results in b = (1/2)[210]. We have also determined that the surface mechanism responsible for the selective growth of Ge on Si over SiO<sub>2</sub> is the high desorption rate of Ge adspecies based on their low desorption activation energy of 42 ± 3 kJ/mol.
Identification of a family of alternatively spliced mRNA species of angiopoietin-1 (2000)

Angiopoietin-1 (Ang-1) is required for developing vessels, and its absence leads to defects in vessel remodeling. Ang-1 has been identified as the ligand for the tyrosine kinase receptor Tie-2, which is expressed specifically on endothelial cells and early hematopoietic cells. In studying the role of Tie-2 and Ang-1 in megakaryocytopoiesis, 3 alternatively spliced species of Ang-1 mRNA (Ang-1.3 kb, Ang-0.9 kb, and Ang-0.7 kb) were identified in addition to the full-length Ang-1 (Ang-1.5 kb), in the megakaryocyte cell line CHRF by reverse transcription-polymerase chain reaction (RT-PCR), and then cloned and sequenced. The expression of 3 alternatively spliced isoforms of Ang-1 was confirmed by RT-PCR using specific primer pairs derived from junction sites and the 3' end of Ang-1 cDNA, and it was further demonstrated by nuclease protection assay, Northern blotting, and immunoblotting in CHRF cells. Expression of the Ang-1.3 kb isoform was also detected in human primary fibroblast cell line FS4, breast cancer cell line MDAMB-468, and CD34(+)CD41(+) cells of fetal liver and platelets. The function of the 1.5-kb, 1.3-kb, and 0.9-kb isoforms was examined. Recombinant proteins Ang-1.5 and 0.9 kb bind strongly to the recombinant Tie-2 receptor (Tie-2-Fc), whereas the 1.3-kb isoform does not. The Ang-1.3 kb isoform binds to the 1.5-kb isoform. Ang-1. 5 kb, but not the 1.3-kb and 0.9-kb isoforms, induces tyrosine phosphorylation of Tie-2 in human umbilical vein endothelial cells. These data suggest that isoforms 1.3 kb and 0.9 kb could serve as dominant negative molecules for the full-length Ang-1. The possible involvement of the newly identified Ang-1 isoforms in angiogenesis and in growth and differentiation of hematopoietic progenitor cells provides a greater complexity to these processes. (Blood. 2000;95:1993-1999)
Structural and functional organization of the colicin E1 operon. (1985)

We analyzed the structural and functional relationships among independently cloned segments of the plasmid ColE1 region that regulates and codes for colicin E1 (cea), immunity (imm), and the mitomycin C-induced lethality function (lys). On the basis of physiological properties, restriction endonuclease mapping, and DNA sequence analysis, the following recombinant plasmids were determined to represent three major functional classes: pNP12 (cea+, imm+, lys+), pNP4 (cea+, imm+, lys-), and pNP6 (cea+, imm-, lys-). Our results have established the order, boundaries, and relative orientation of the three structural genes, the location of the promoter region for imm gene transcription, and the predicted amino acid sequences of the imm and lys gene products. Hydropathicity analysis suggests that both proteins have hydrophobic amino acid segments characteristic of membrane-associated proteins. A model for the structure and expression of the colicin E1 operon is proposed in which the cea and lys genes are expressed from a single inducible promoter that is controlled by the lexA repressor in response to the SOS system of Escherichia coli. The imm gene lies between the cea and lys genes and is expressed by transcription in the opposite direction from a promoter located within the lys gene. This arrangement of structural genes indicates that the transcriptional units for all three genes overlap. We suggest that the formation of anti-sense RNA may be an important element in the coordinate regulation of gene expression in this system.
CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer (2007)

Activation of PI3K is among the earliest signaling events observed in T cells after conjugate formation with antigen-presenting cells (APCs). The relevant PI3K catalytic isoform and relative contribution of the TcR and CD28 to PI3K activity at the immune synapse have not been determined unequivocally. Using a quantitative imaging-based assay, we show that the PI3K activity at the T cell-APC contact area is dependent on the p110delta, but not the p110gamma, isoform of PI3K. CD28 enhanced PIP3 production at the T-cell synapse independently of its YMNM PI3K-recruitment motif that instead was required for efficient PKC recruitment. CD28 could partially compensate for the lack of p110delta activity during T-cell activation, which indicates that CD28 and p110delta act in parallel and complementary pathways to activate T cells. Consistent with this, CD28 and p110delta double-deficient mice were severely immune compromised. We therefore suggest that combined pharmaceutic targeting of p110delta activity and CD28 costimulation has potent therapeutic potential.
Blood-Brain Barrier Transport of Opioid Analgesics (2011)

Opioid analgesics exhibit cationic properties under physiological conditions, and the mechanism underlying permeation of the blood-brain barrier thus cannot be fully explained by simple diffusion alone. Various types of transporters that exhibit substrate specificity are localized on the blood-brain barrier, and play a role in transporting substances from circulating blood and from brain interstitial fluid. Progress is being made in explaining the mechanisms, functions, and physiological roles of polyspecific organic cation transporters, but little evidence has indicated that these previously identified organic cation transporters are involved in the transport of opioid analgesics across the blood-brain barrier. Consequently, clarifying the role of transporters in the distribution of opioid analgesics into the brain and determining their transport molecule will not only provide clues to effective drug delivery to the brain, but will also contribute to optimizing pain relief treatment, and by extension play a role in drug discovery for analgesics. Currently there are enthusiastic discussions in the literature regarding the existence of putative transporters involved in the transport of opioid analgesics across the blood-brain barrier. This review article introduces the results of our research as well as recent findings on the involvement of transporters in the blood-brain barrier transport of opioid analgesics such as morphine, morphine metabolites, oxycodone, fentanyl, codeine, and pentazocine.
Site-Specific Hydrolytic Cleavage of Cytochrome c and of Its Heme Undecapeptide, Promoted by Coordination Complexes of Palladium(II) (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSite-Specific Hydrolytic Cleavage of Cytochrome c and of Its Heme Undecapeptide, Promoted by Coordination Complexes of Palladium(II)Longgen Zhu, Ling Qin, Tatjana N. Parac, and Nenad M. KosticCite this: J. Am. Chem. Soc. 1994, 116, 12, 5218–5224Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/ja00091a028https://doi.org/10.1021/ja00091a028research-articleACS PublicationsRequest reuse permissionsArticle Views470Altmetric-Citations96LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Natural Soluble Interleukin-15Rα Is Generated by Cleavage That Involves the Tumor Necrosis Factor-α-converting Enzyme (TACE/ADAM17) (2004)

This study shows that the high affinity alpha-chain of the interleukin (IL)-15 receptor exists not only in membrane-anchored but also in soluble form. Soluble IL-15Ralpha (sIL-15Ralpha) can be detected in mouse sera and cell-conditioned media by enzyme-linked immunosorbent assay and by immunoprecipitation and Western blotting. This protein has a molecular mass of about 30 kDa because of the presence of a single N-glycosylation site, which is reduced to 26 kDa after N-glycosidase treatment. Transmembrane IL-15Ralpha is constitutively converted into its soluble form by proteolytic cleavage that involves tumor necrosis factor-alpha-converting enzyme (TACE), and this process is further enhanced by phorbol 12-myristate 13-acetate (PMA) stimulation. The hydroxamate GW280264X, which is capable of blocking TACE and the closely related disintegrin-like metalloproteinase 10 (ADAM10), effectively inhibited both spontaneous and PMA-inducible cleavage of IL-15Ralpha, whereas GI254023X, which preferentially blocks ADAM10, was ineffective. Overexpression of TACE but not ADAM10 in COS-7 cells enhanced the constitutive and PMA-inducible cleavage of IL-15Ralpha. Moreover, murine fibroblasts deficient in TACE but not ADAM10 expression exhibited a significant reduction in the spontaneous and inducible IL-15Ralpha shedding, whereas a reconstitution of TACE in these cells restored the release of sIL-15Ralpha, thereby suggesting that TACE-mediated proteolysis may represent a major mechanism for sIL-15Ralpha generation in mice. The existence of natural sIL-15Ralpha offers novel insights into the complex biology of IL-15 and envisages a new level for therapeutic intervention.
GTPases and T cell activation (2003)

Guanine nucleotide binding proteins rapidly cycle between a guanosine diphosphate (GDP)-bound and guanosine triphosphate (GTP)-bound state, and they operate as binary switches that control cell activation in response to environmental cues. GTPases adopt different conformations when binding GTP vs. GDP. The GTP-bound state is generally considered to be the active conformation that allows GTPases to interact with downstream effectors and thereby initiate downstream signaling pathways, which regulate many important biological processes. Many members of the Ras family of GTPases, notably Ras and Rap1A, and the Rho family GTPases, Cdc42Hs, Rac1, Rac2 and RhoA, are important components of signal transduction pathways used by antigen receptors, costimulatory, cytokine and chemokine receptors to regulate the immune response. This review discusses current knowledge and ideas about the regulation and function of these GTPases in lymphocytes.
Structure of Neuroblastoma Suppressor of Tumorigenicity 1 (NBL1) (2015)

Bone morphogenetic proteins (BMPs) are antagonized through the action of numerous extracellular protein antagonists, including members from the differential screening-selected gene aberrative in neuroblastoma (DAN) family. In vivo, misregulation of the balance between BMP signaling and DAN inhibition can lead to numerous disease states, including cancer, kidney nephropathy, and pulmonary arterial hypertension. Despite this importance, very little information is available describing how DAN family proteins effectively inhibit BMP ligands. Furthermore, our understanding for how differences in individual DAN family members arise, including affinity and specificity, remains underdeveloped. Here, we present the structure of the founding member of the DAN family, neuroblastoma suppressor of tumorigenicity 1 (NBL1). Comparing NBL1 to the structure of protein related to Dan and Cerberus (PRDC), a more potent BMP antagonist within the DAN family, a number of differences were identified. Through a mutagenesis-based approach, we were able to correlate the BMP binding epitope in NBL1 with that in PRDC, where introduction of specific PRDC amino acids in NBL1 (A58F and S67Y) correlated with a gain-of-function inhibition toward BMP2 and BMP7, but not GDF5. Although NBL1(S67Y) was able to antagonize BMP7 as effectively as PRDC, NBL1(S67Y) was still 32-fold weaker than PRDC against BMP2. Taken together, this data suggests that alterations in the BMP binding epitope can partially account for differences in the potency of BMP inhibition within the DAN family.
Towards a comprehensive structural variation map of an individual human genome (2010)

Our results indicate that a large number of structural variants have been unreported in the individual genomes published to date. This significant extent and complexity of structural variants, as well as the growing recognition of their medical relevance, necessitate they be actively studied in health-related analyses of personal genomes. The new catalogue of structural variants generated for this genome provides a crucial resource for future comparison studies.
Influence of subinhibitory concentrations of loracarbef (LY 163892) and daptomycin (LY 146032) on bacterial phagocytosis, killing and serum sensitivity (1990)

The aim of this study was to evaluate whether pre-exposure of bacteria to a subinhibitory concentration (sub-MIC) of loracarbef (LY 163892) or daptomycin (LY 146032) could modify bacterial susceptibility to serum bactericidal activity and to phagocytosis and killing by murine peritoneal macrophages and by human polymorphonuclear leucocytes. Escherichia coli, Haemophilus influenzae type b and Staphylococcus aureus grown in the presence of one quarter the MIC of loracarbef, and S. aureus exposed to one quarter the MIC of daptomycin were phagocytosed and killed in numbers significantly higher than non-exposed bacteria. Pre-exposure to loracarbef resulted in increased susceptibility of E. coli and H. influenzae type b to the bactericidal activity of antiserum, but exposure to loracarbef or daptomycin did not modify serum sensitivity of S. aureus. Loracarbef treatment and antiserum enhanced phagocytosis and killing of E. coli and H. influenzae type b to a greater extent than either antibiotic treatment or antiserum alone. These data indicate that loracarbef and daptomycin at sub-MIC enhance the susceptibility of bacterial pathogens to cellular and host defence mechanisms.