gebhart/patrepeval huggingface dataset:
The Biochemical Pathway Mediating the Proliferative Response of Bone Cells to a Mechanical Stimulus* (1996)

Calvarial bone cells of rats were subjected to either a cyclic biaxial strain of 0.17 per cent (1700 microstrain) or a hydrostatic pressure of 2.5, five, or ten pounds per square inch (17.2, 34.5, or sixty-nine kilopascals). The frequency was held constant at one hertz for both types of mechanical stimulation. When cultured bone cells that had been subjected to a cyclic biaxial strain for two hours were harvested twenty-two hours later, it was found that the level of prostaglandin E2 had increased significantly (p < 0.01) as had cellular proliferation (p < 0.01), as indicated by the incorporation of [3H]-thymidine. The addition to the medium of indomethacin, an inhibitor of prostaglandin synthesis, at a ten-micromolar concentration significantly inhibited (p < 0.01) the increase in prostaglandin E2 synthesis but had no effect on the strain-induced increase in cellular proliferation, as indicated by the incorporation of [3H]-thymidine. Twenty-four hours after exposure to the same cyclic biaxial strain for thirty seconds, other cultured bone cells showed a significant increase in the level of cytoskeletal calmodulin (p < 0.05) and in the DNA content (p < 0.05). N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), a calmodulin antagonist, was added to the medium at a one-micromolar concentration, which had been shown to have no effect on the increase in the DNA content of control cells; W-7 completely blocked the increase in the level of cytoskeletal calmodulin and in the DNA content in the cells that were subjected to a cyclic biaxial strain. The bone cells subjected to a hydrostatic pressure showed a dose-dependent increase in the concentration of cytosolic Ca2+, as measured with Fura 2-AM, a fluorescent indicator of intracellular calcium. With a pressure of ten pounds per square inch (sixty-nine kilopascals), the increase in the concentration of cytosolic Ca2+ was nearly eight times greater than that at 2.5 pounds per square inch (17.2 kilopascals) (126 +/- 15.2 compared with 16 +/- 8.0 nanomolar, mean and standard deviation). The addition to the medium of neomycin, an inhibitor of the inositol phosphate cascade, at a ten-millimolar concentration completely blocked the increase in the concentration of cytosolic Ca2+ in these cells; this concentration of neomycin had been shown to have no effect on proliferation in control bone cells. There was also a dose-dependent relationship between the duration of the stimulus and the cellular proliferation. Remarkably, one cycle of pressure at ten pounds per square inch (sixty-nine kilopascals) and a frequency of approximately one hertz produced a 57 per cent increase in the incorporation of [3H]-thymidine at twenty-four hours (p < 0.001). From these findings, we hypothesized that the inositol phosphate cascade-cytosolic Ca(2+)-cytoskeletal calmodulin system plays a dominant role in the signal transduction of a mechanical stimulus into increased proliferation of bone cells, at least under the conditions reported here.
Signaling Through the Hematopoietic Cytokine Receptors (1995)

Hematopoiesis is regulated through the interaction of a variety of growth factors with specific receptors of the cytokine receptor superfamily. Although lacking catalytic domains, all the receptors couple ligand binding to the rapid induction of protein tyrosine phosphorylation. This is mediated through a novel family of protein tyrosine kinases termed the Janus kinases (Jaks) which associate with the receptors and are activated following ligand binding. Depending upon the cytokine/receptor system, one or more of the four known Jaks (Jak1, Jak2, Jak3, Tyk2) is/are involved. The activated Jaks phosphorylate both themselves and the receptor subunits, creating docking sites for SH2-containing proteins including SHC, which couples receptor engagement to activation of the ras pathway, and HCP, a protein tyrosine phosphatase which negatively affects the response. In addition, the Jaks phosphorylate one or more of a family of signal transducers and activators of transcription (Stats). Phosphorylation of Stats induces their nuclear translocation and DNA-binding activity. Activation of Stats is independent of activation of the ras pathway and represents a novel signaling pathway correlated with mitogenesis.
Generation of Mucosal Dendritic Cells from Bone Marrow Reveals a Critical Role of Retinoic Acid (2010)

It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that a subset of bone marrow cells freshly isolated from C57BL/6 mice express the retinoic acid (RA)-synthesizing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1a2) and are capable of providing RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs to express CCR9 and ALDH1a2 and conferred upon them mucosal DC functions, including induction of Foxp3(+) regulatory T cells, IgA-secreting B cells, and gut-homing molecules. This response of DCs to RA was dependent on a narrow time window and stringent dose effect. RA promoted bone marrow-derived DC production of bioactive TGF-β by inhibiting suppressor of cytokine signaling 3 expression and thereby enhancing STAT3 activation. These RA effects were evident in vivo, in that mucosal DCs from vitamin A-deficient mice had reduced mucosal DC function, namely failure to induce Foxp3(+) regulatory T cells. Furthermore, MyD88 signaling enhanced RA-educated DC ALDH1a2 expression and was required for optimal TGF-β production. These data indicate that RA plays a critical role in the generation of mucosal DCs from bone marrow and in their functional activity.
The Role of C5 in Septic Lung Injury (1985)

One proposed mechanism for the pathogenesis of lung injury in septic animals is the stimulation by C5a of granulocytes to produce and release toxic oxygen radicals that damage cellular membranes in pulmonary capillaries. The authors have investigated the possible role of C5 in septic lung injury, utilizing C5-sufficient and C5-deficient twin mice strains. In this lethal sepsis model, mean survival time is increased in C5-deficient mice in comparison to the survival of their C5-sufficient twins. Morphometric results demonstrate a significant increase in intracapillary granulocrit and air-blood barrier thickness 24 hours after cecal ligation and puncture in C5-sufficient septic mice. Similarly, mean arterial pO2 is significantly decreased in the C5-sufficient animals. Intracapillary granulocrit, air-blood barrier thickness, and arterial pO2 are normal in the septic C5-deficient twins of these animals. These data support the hypothesis that C5 is involved in the pathogenesis of septic lung injury.
A Virus in a Fungus in a Plant: Three-Way Symbiosis Required for Thermal Tolerance (2007)

A mutualistic association between a fungal endophyte and a tropical panic grass allows both organisms to grow at high soil temperatures. We characterized a virus from this fungus that is involved in the mutualistic interaction. Fungal isolates cured of the virus are unable to confer heat tolerance, but heat tolerance is restored after the virus is reintroduced. The virus-infected fungus confers heat tolerance not only to its native monocot host but also to a eudicot host, which suggests that the underlying mechanism involves pathways conserved between these two groups of plants.
Effect of NKTR-214 on the number and activity of CD8+ tumor infiltrating lymphocytes in patients with advanced renal cell carcinoma. (2017)

454 Background: Patients with low baseline CD8+ T-cells within the tumor microenvironment (TILs) have a poor response to immune checkpoint inhibitors. Agents designed to specifically activate and expand CD8+ T cells may improve clinical outcomes in patients with low TILs. NKTR-214 is a CD-122-biased agonist designed to provide sustained signaling through the heterodimeric IL-2 receptor pathway (IL-2Rβɣ) and preferentially activate and expand NK and effector CD8+ T cells over CD4+ T regulatory cells. Methods: A dose escalation, open-label, trial was initiated to assess the safety of NKTR-214 and explore immune changes in the blood and tumor microenvironment in patients with advanced solid tumors. NKTR-214 was administered IV in an outpatient setting with initial dosing at 0.003 mg/kg. Pre and post treatment blood and tumor samples were analyzed for immune phenotyping, gene expression, T cell receptor diversity, and changes in the tumor microenvironment by immunohistochemistry. Results: Among 25 patients dosed, 15 had RCC (10@0.006mg/kg, 4@0.009mg/kg, and 1@0.012mg/kg). Treatment with NKTR-214 was well tolerated and the MTD was not reached. One patient experienced DLTs (Gr3 syncope and hypotension) at 0.012 mg/kg. There were no immune-related AEs. Of 12 patients evaluable for response, 75% had SD at their first on treatment scan. Of 5 patients, who were immune checkpoint naïve with ≥ 1 prior TKI treatments, 3 experienced tumor shrinkage, 1 with PR per RECIST 1.1 (unconfirmed). Interrogation of the tumor microenvironment revealed many significant immunological changes post treatment, including increase in total and proliferating NK, CD8+, and CD4+ T cells. There was good correlation between increase in activated CD4+ and CD8+ T cells in peripheral blood with an increase in T cell infiltrates within the tumor tissue. Conclusions: NKTR-214 increased immune infiltration in the tumor and anti-tumor activity in patients who previously progressed on TKIs, with a favorable safety profile. The ability to alter the immune environment and increase PD-1 expression on effectors T cells may improve the effectiveness of anti-PD-1 blockade. A trial combining NKTR-214 and nivolumab is enrolling. Clinical trial information: 02869295.
Binding of alkaline‐earth metal cations and some anions to hosphatidylcholine liposomes (1987)

The dependence of electrophoretic mobility of multilamellar liposomes composed of egg phosphatidylcholine (PtdCho), dimyristoyl-glycerophosphocholine (Myr2Gro-P-Cho) and dipalmitoyl-glycerophosphocholine (Pam2-Gro-P-Cho) on the concentration of several cations and anions has been measured. Values of surface densities of binding sites and intrinsic binding constants of ions to liposome membranes were determined by processing the results in the framework of Gouy-Stern theory. Sharp reductions in the positive surface potential of Myr2Gro-P-Cho and Pam2Gro-P-Cho liposomes have been detected at the thermotropic transition of the lipids from the gel to liquid-crystalline phase. Similar alterations of liposome surface potential were revealed at the temperature of pretransition, as well as at about 50 degrees C, in the case of Pam2Gro-P-Cho. A model is suggested for ion binding to PtdCho membranes, according to which the ion-binding sites are considered as point defects (vacancies) in the structure of lipid head-groups arranged over a trigonal lattice.
Enzyme entrapment in electrically conducting polymers. Immobilisation of glucose oxidase in polypyrrole and its application in amperometric glucose sensors (1986)

A technique is described for the entrapment of glucose oxidase in a polypyrrole matrix electrochemically deposited on a printed platinum electrode. The enzyme activity incorporated into the polymer was quantified by spectrophotometric assay using a flow-through cell and found to be proportional to the activity in the electropolymerisation medium. Polymer-entrapped glucose oxidase electrodes can be operated as amperometric glucose sensors in the presence or absence of soluble mediators. These electrodes respond rapidly, reaching a steady state within 20–40 s, with the enzymatic response being current limiting. The potential of this new immobilisation technique to the development of biosensors is discussed.
Regiospecific synthesis of 2‐substituted furanonaphthoquinones (2000)

Abstract The naturally‐occurring furanonaphthoquinones 1a‐d have been synthesized from 3‐furancarboxylic acid and 2,3‐dimethoxybenzaldehyde via the Birch reduction‐elimination.
TRANSPLANTATION TIMELINE MANKINDʼS (1991)

The Division of Immunology and Organ Transplantation, Department of Surgery, The University of Texas Medical School at Houston, Houston, Texas 77030
The biosynthetic gene cluster for sophorolipids: a biotechnological interesting biosurfactant produced by Starmerella bombicola (2013)

Sophorolipids are promising biological derived surfactants or detergents which find application in household cleaning, personal care and cosmetics. They are produced by specific yeast species and among those, Starmerella bombicola (former Candida bombicola) is the most widely used and studied one. Despite the commercial interest in sophorolipids, the biosynthetic pathway of these secondary metabolites remained hitherto partially unsolved. In this manuscript we present the sophorolipid gene cluster consisting of five genes directly involved in sophorolipid synthesis: a cytochrome P450 monooxygenase, two glucosyltransferases, an acetyltransferase and a transporter. It was demonstrated that disabling the first step of the pathway - cytochrome P450 monooxygenase mediated terminal or subterminal hydroxylation of a common fatty acid - results in complete abolishment of sophorolipid production. This phenotype could be complemented by supplying the yeast with hydroxylated fatty acids. On the other hand, knocking out the transporter gene yields mutants still able to secrete sophorolipids, though only at levels of 10% as compared with the wild type, suggesting alternative routes for secretion. Finally, it was proved that hampering sophorolipid production does not affect cell growth or cell viability in laboratory conditions, as can be expected for secondary metabolites.
Rational design of receptor-specific variants of human growth hormone. (1991)

Human growth hormone (hGH) binds to both the growth hormone (GH) and the prolactin (PRL) receptors. Competition experiments followed by mutational analysis show that the epitope on hGH for hPRL receptor consists of strong determinants in the middle of helix 1 (comprising residues His-18, His-21, and Phe-25), a loop region (including Ile-58, Ser-62, and Asn-63), and the central portion of helix 4 (containing residues Arg-167, Lys-168, Lys-172, Glu-174, Phe-176, and Arg-178). When these residues are mapped on a structural model of hGH, they form a patch that overlaps but is not identical to that previously determined for the hGH receptor. Three of these side chains (His-18, His-21, and Glu-174) are ligands for binding Zn2+, which is required for high-affinity hGH-hPRL receptor complex formation. By introducing pairs of mutations into hGH that exploit the zinc dependency for hPRL receptor binding and remove side chains in the nonoverlapping regions, we have shifted the binding preference toward the hGH receptor by a factor of 34,000 or toward the hPRL receptor by a factor of 150 without substantial loss in binding affinity for the preferred receptor. The energetic effects of the individual mutations are additive within the double mutants, suggesting that each functions independently and does not introduce gross perturbations in structure. Such receptor-selective variants of hGH should be useful molecular probes to link specific receptor binding events to the various biological activities of hGH.
Flow Classification of Encrypted Traffic Streams using Multi-fractal Features (2018)

The increased usage of encrypted application layer traffic is making it harder for traditional traffic categorization methods like deep packet inspection to function. Without ways of categorizing traffic, network service providers have a hard time optimizing traffic flows, resulting in worse quality of experience for the end user. Recent solutions to this problem typically apply some statistical measurements on network flows and use the resulting values as features in a machine learning model. However, by utilizing recent advances in multi-fractal analysis, multi-fractal features can be extracted from time-series via wavelet leaders, which can be used as features instead. In this thesis, these features are used exclusively, together with support vector machines, to build a model that categorizes encrypted network traffic into six categories that, according to a report, accounts for over 80% of the mobile traffic composition. The resulting model achieved a F1-score of 0.958 on synthetic traffic while only using multi-fractal features, leading to the conclusion that incorporating multi-fractal features in a traffic categorization framework, implemented at a base station, would be beneficial for the categorization score for such a framework.
Novel Saccharide-Photoinduced Electron Transfer Sensors Based on the Interaction of Boronic Acid and Amine (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel Saccharide-Photoinduced Electron Transfer Sensors Based on the Interaction of Boronic Acid and AmineTony D. James, K. R. A. Samankumara Sandanayake, Ritsuko Iguchi, and Seiji ShinkaiCite this: J. Am. Chem. Soc. 1995, 117, 35, 8982–8987Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/ja00140a013https://doi.org/10.1021/ja00140a013research-articleACS PublicationsRequest reuse permissionsArticle Views5446Altmetric-Citations410LEARN 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
The Chemistry of Enamel Caries (2000)

The chemical changes which occur during the process of carious destruction of enamel are complex due to a number of factors. First, substituted hydroxyapatite, the main component of dental enamel, can behave in a very complex manner during dissolution. This is due not only to its ability to accept substituent ions but also to the wide range of calcium phosphate species which can form following dissolution. In addition, the composition, i.e., the extent of substitution, changes throughout enamel in the direction of carious attack, i.e., from surface to interior. Both surface and positively birefringent zones of the lesion clearly illustrate that carious destruction is not simple dissolution. Selective dissolution of soluble minerals occurs, and there is the probability of reprecipitation. The role of fluoride here is crucial in that not only does it protect enamel per se but also its presence in solution means that rather insoluble fluoridated species can form very easily, encouraging redeposition. The role of organic material clearly needs further investigation, but there is the real possibility of both inhibition of repair and facilitation of redeposition. For the future, delivering fluoride deep into the lesion would appear to offer the prospect of improved repair. This would entail a delivery vehicle which solved the problem of fluoride uptake by apatite at the tooth surface. Elucidation of the role of organic material may also reveal putative mechanisms for encouraging repair and/or protecting the enamel mineral.
Green Fluorescent Protein as a Transcriptional Reporter in Epithelial Cells: Real-Time Studies of the Human Involucrin Promoter (2002)

Green Fluorescent Protein (GFP) is a popular reporter for numerous uses in mammalian cells because its activity can be measured directly without cofactors or reagents. We show that an improved GFP variant, the cycle-three GFP gene in the pGlow-TOPO® vector is useful as a reporter of mammalian promoter activity. The 5´ regulatory region from the human involucrin gene was cloned upstream of the cycle-three GFP gene and the resultant constructs transfected into C33-A epithelial tumor cells and normal keratinocytes. Fluorescence analysis whole cells showed that cyclethree GFP in pGlow-TOPO® is reliable for reporting mammalian promoter function under different conditions. GFP activity was comparable to that of CAT, indicating that this method can be used in transcriptional studies for numerous mammalian promoters.
On visible surface generation by a priori tree structures (1980)

This paper describes a new algorithm for solving the hidden surface (or line) problem, to more rapidly generate realistic images of 3-D scenes composed of polygons, and presents the development of theoretical foundations in the area as well as additional related algorithms. As in many applications the environment to be displayed consists of polygons many of whose relative geometric relations are static, we attempt to capitalize on this by preprocessing the environment's database so as to decrease the run-time computations required to generate a scene. This preprocessing is based on generating a “binary space partitioning” tree whose in order traversal of visibility priority at run-time will produce a linear order, dependent upon the viewing position, on (parts of) the polygons, which can then be used to easily solve the hidden surface problem. In the application where the entire environment is static with only the viewing-position changing, as is common in simulation, the results presented will be sufficient to solve completely the hidden surface problem.
Polymer encapsulated neurotransmitter secreting cells. Potential treatment for Parkinson's disease. (1992)

Parkinson's disease, a neurologic disorder characterized by a dopamine deficit within the striatum, may be improved by transplantation of polymer encapsulated neurosecretory cells. Surrounding cells with a selectively permeable barrier offers several advantages, including preventing immune rejection and tumor formation while allowing functional efficacy. Bovine adrenal medullary chromaffin cells, or PC12 cells, a rat-derived pheochromocytoma cell line, were encapsulated within polyelectrolyte-based microcapsules or thermoplastic-based macrocapsules. Histologic and biochemical analyses revealed that both types of cells survived and that neurotransmitter release from capsules was sustained for several months in vitro, irrespective of the encapsulation method employed. Both of the encapsulation systems protected the enclosed cells from an immunologic challenge in vitro, and prevented immune rejection when cell containing capsules were implanted in an immunologically incompatible host. Chromaffin or PC12 cell containing capsules implanted into the dopamine (DA) depleted striatum of rats reduced the lesion associated functional deficit. These results suggest that encapsulated neurosecretory cell implants may be useful in treating various central nervous system (CNS) deficits, particularly in cases involving a specific neurochemical lesion.
Prevention of hyperacute xenograft rejection through direct thrombin inhibition with hirudin. (2011)

Direct thrombin inhibition with Hirudin could be a successful strategy in primate xenotransplantation experiments to prevent tissue damage thus improving the graft survival.