gebhart/patrepeval huggingface dataset:
JAK2Mutations in Polycythemia Vera — Molecular Mechanisms and Clinical Applications (2007)

Janus kinase 2 (JAK2) is a cytoplasmic tyrosine kinase that transduces signals, especially those triggered by hematopoietic growth factors such as erythropoietin, in normal and neoplastic cells. In March and April 2005, four groups of investigators reported finding an acquired JAK2 mutation (termed JAK2 V617F) in association with polycythemia vera and related myeloproliferative disorders.1 These seminal reports have already been cited many times, and JAK2 is now a target for the development of new treatments for the myeloproliferative disorders. JAK2 V617F is detectable in more than 95% of patients who have polycythemia vera, as defined according to conventional criteria. The . . .
Field Cage Studies and Progressive Evaluation of Genetically-Engineered Mosquitoes (2013)

Our results indicate that OX3604C may not be effective in large-scale releases. A strain with the same transgene that is not encumbered by a large mating disadvantage, however, could have improved prospects for dengue prevention. Insights from large outdoor cage experiments may provide an important part of the progressive, stepwise evaluation of genetically-engineered mosquitoes.
An Introduction to molecular electronics (1996)

Theory photochromics and electrochromics piezoelectric and pyroelectronic materials liquid crystals and devices organics for nonlinear optics conducting polymers charge transfer complexes LB films magnetism ion transport/biological systems biosensors biomolecular optoelectronics STM/APM molecular electronic logic and architectures molecular MBE.
Biodegradable microspheres targeting mucosal immune-regulating cells: new approach for treatment of inflammatory bowel disease. (2003)

Several studies have indicated that active monocytes, such as macrophages and T cells, play an important role in the pathogenesis of chronic human inflammatory bowel disease (IBD), although the etiology remains unclear. Manipulation of these cells appears essential for the treatment of patients with IBD. Recently, considerable attention has been paid to the use of polymer microspheres for the sustained release of various drugs and the targeting of therapeutic agents to their site of action. It was reported that biodegradable poly-D,L-lactic acid (PDLLA) microspheres can be efficiently taken up by macrophages and M cells. We evaluated the effect of a new drug delivery system targeting microfold cells and macrophages with PDLLA microspheres and gelatin microspheres (GM) on colitis models. In the first experiment, colitis was induced in Balb/c mice by 5% dextran sodium sulfate, and microspheres containing dexamethsone (Decadrone, Dx; Dx microspheres) were orally administered to these mice. Serum levels of Dx did not reach a detectable level after administration of Dx microspheres. The tissue distribution of microspheres containing 125I-Dx in inflamed colon was significantly higher than that in other organs. The histological score, myeloperoxidase activity, and nitric oxide production of mice treated with Dx microspheres were significantly lower than in those treated with Dx alone. Gene expression of proinflammatory cytokines was remarkably downregulated in mice treated with Dx microspheres compared to Dx alone. Next, we investigated the effect of elimination of resident macrophages using microspheres containing dichloromethylene diphosphonate (DMDP) on IL-10 knockout mice. We administered DMDP microspheres to IL-10 KO mice rectally and assessed whether this reagent could reduce the number of local Mac-1-positive cells in the intestine and suppress the development of colitis in IL-10 KO mice. DMDP microspheres reduced the numbers of resident macrophages in the colon of IL-10 KO mice but did not reduce the percentage of Mac-1-positive cells in the spleen, peritoneal cavity, or mesenteric lymph nodes. Depletion of intestinal macrophages significantly suppressed development of chronic colitis in IL-10 KO mice, however. Third, we developed gelatin microspheres containing IL-10, which can be released sustainedly to a local site without losing bioactivity. We administered these microspheres to IL-10 KO mice rectally to investigate whether this treatment can ameliorate colitis. Colonic inflammation in mice treated with GM-IL-10 is remarkably reduced compared to those treated with IL-10 alone. Moreover, expression of CD 40 on Mac-1-positive cells treated with GM-IL-10 is decreased more notably than in mice treated with IL-10 alone. These data suggest that a drug delivery system using these microspheres containing immunomodulatory agents may be a therapeutic approach to human IBD.
Comparison of the Influenza Virus-Specific Effector and Memory B-Cell Responses to Immunization of Children and Adults with Live Attenuated or Inactivated Influenza Virus Vaccines (2006)

Cellular immune responses to influenza virus infection and influenza virus vaccination have not been rigorously characterized. We quantified the effector and memory B-cell responses in children and adults after administration of either live attenuated (LAIV) or inactivated (TIV) influenza virus vaccines and compared these to antibody responses. Peripheral blood mononuclear cells were collected at days 0, 7 to 12, and 27 to 42 after immunization of younger children (6 months to 4 years old), older children (5 to 9 years old), and adults. Influenza virus-specific effector immunoglobulin A (IgA) and IgG circulating antibody-secreting cells (ASC) and stimulated memory B cells were detected using an enzyme-linked immunospot assay. Circulating influenza virus-specific IgG and IgA ASC were detected 7 to 12 days after TIV and after LAIV immunization. Seventy-nine percent or more of adults and older children had demonstrable IgG ASC responses, while IgA ASC responses were detected in 29 to 53% of the subjects. The IgG ASC response rate to LAIV immunization in adults was significantly higher than the response rate measured by standard serum antibody assays (26.3% and 15.8% by neutralization and hemagglutination inhibition assays, respectively). IgG ASC and serum antibody responses were relatively low in the younger children compared to older children and adults. TIV, but not LAIV, significantly increased the percentage of circulating influenza virus-specific memory B cells detected at 27 to 42 days after immunization in children and adults. In conclusion, although both influenza vaccines are effective, we found significant differences in the B-cell and antibody responses elicited after LAIV or TIV immunization in adults and older children and between young children and older age groups.
Investigation of nucleic acid secondary structure by means of chemical modification with a carbodiimide reagent. I. Reaction between N-cyclohexyl-N'-β-(4-methylmorpholinium)ethylcarbodiimide and model nucleotides (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInvestigation of nucleic acid secondary structure by means of chemical modification with a carbodiimide reagent. I. Reaction between N-cyclohexyl-N'-β-(4-methylmorpholinium)ethylcarbodiimide and model nucleotidesDavid Henry Metz and Geoffrey L. BrownCite this: Biochemistry 1969, 8, 6, 2312–2328Publication Date (Print):June 1, 1969Publication History Published online1 May 2002Published inissue 1 June 1969https://doi.org/10.1021/bi00834a012Request reuse permissionsArticle Views143Altmetric-Citations41LEARN 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 InReddit PDF (2 MB) Get e-Alertsclose Get e-Alerts
Vanadium(IV) causes 2'-deoxyguanosine hydroxylation and deoxyribonucleic acid damage via free radical reactions. (1996)

Vanadium(IV) caused molecular oxygen dependent 2'-deoxyguanosine (dG) hydroxylation to form 8-hydroxyl-2'-deoxyguanosine (8-OHdG). During a 15-minute incubation of 1.0 mM dG and 1.0 mM VOSO4 (vanadium(IV)) in phosphate buffer solution (pH 7.4) at room temperature under ambient air, dG was converted to 8-OHdG with a yield of about 0.31 percent. Catalase and formate inhibited the 8-OHdG formation while superoxide dismutase enhanced it. Diethylenetriaminepentaacetic acid (DTPA) and deferoxamine blocked the 8-OHdG formation. Incubation of vanadium(IV) with dG in argon did not generate any significant amount of 8-OHdG, indicating the role of molecular oxygen in the mechanism of vanadium(IV)-induced dG hydroxylation. Vanadium(IV) also caused molecular oxygen dependent deoxyribonucleic acid (DNA) strand breaks in a pattern similar to that observed for dG hydroxylation. Reaction of vanadium(IV) with H2O2 generated OH radicals, which were inhibited by DTPA and deferoxamine. Incubation of vanadium(IV) with dG or with DNA in the presence of H2O2 resulted in an enhanced 8-OHdG formation and substantial DNA strand breaks. Reaction of vanadium(IV) with t-butyl hydroperoxide generated hydroperoxide-derived free radicals, which caused 8-OHdG formation from dG and DNA strand breaks.
Photomodulated Blocking of Gramicidin Ion Channels (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPhotomodulated Blocking of Gramicidin Ion ChannelsLinda Lien, Dominic C. J. Jaikaran, Zhihua Zhang, and G. Andrew WoolleyView Author Information Department of Chemistry, University of Toronto 80 St. George Street, Toronto, M5S 3H6, Canada Cite this: J. Am. Chem. Soc. 1996, 118, 48, 12222–12223Publication Date (Web):December 4, 1996Publication History Received1 July 1996Published online4 December 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja962217shttps://doi.org/10.1021/ja962217srapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views1003Altmetric-Citations72LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Azobenzene,Conformation,Isomerization,Organic compounds,Reaction products Get e-Alerts
Induction of an immune response by oral administration of recombinant botulinum toxin (1997)

A gene encoding the full-size botulinum neurotoxin serotype C was reconstructed in vector pQE-30 and expressed at high levels in Escherichia coli. Three amino acid mutations (H229-->G, E230-->T, and H233-->N) were generated in the zinc-binding motif, resulting in complete detoxification of the modified recombinant holotoxin. The PCR-amplified wild-type light chain of botulinum neurotoxin serotype C was also expressed in E. coli and used as a control in all experiments. Modified recombinant holotoxin and light chain contained a histidine affinity tag at the amino terminus, which was used for detection and purification. Recombinant proteins were purified on nickel affinity resin and analyzed by Western blotting with the anti-histidine tag and anti-neurotoxin C antibodies. The results indicated that the 150-kDa molecule of modified recombinant holotoxin and the 50-kDa recombinant light chain were synthesized without degradation; however, E. coli did not provide for efficient nicking of modified recombinant toxin. Modified recombinant holotoxin was not toxic to mice, had no effect on nerve-evoked muscle twitch in vitro, and was not able to cleave syntaxin in crude synaptosome preparations. The recombinant light chain was also nontoxic in vivo, had no effect on evoked muscle twitch, but was able to cleave syntaxin. Modified recombinant neurotoxin and light chain were administered to animals either orally or subcutaneously. Both oral administration and subcutaneous administration of modified recombinant neurotoxin evoked high levels of serum antibodies and protective immunity. Oral administration of recombinant light chain evoked no systemic response, whereas subcutaneous administration evoked antibody production and immunity.
Cytokines in Haemopoietic Progenitor Mobilisation for Peripheral Blood Stem Cell Transplantation (2002)

Haemopoietic progenitors mobilised into peripheral blood are now almost universally used in autologous haemopoietic stem cell transplantation in the treatment of a range of malignant and some nonmalignant disease. Although chemotherapy alone was initially used, all modern protocols now involve the use of cytokines, with or without chemotherapy. Important developments have included an in understanding of the importance of prior cancer therapy on progenitor yield, knowledge of the kinetics of mobilisation and development of necessary skills to collect and cryopreserve progenitors. More accurate measurement of haemopoietic progenitors and definitions of target cell yields for optimal haemopoietic recovery after high-dose therapy have also contributed to more predictable outcomes and provide a reference point for newer mobilisation approaches. Although G-CSF based regimens are usually successful, some patients either fail to mobilise sufficient progenitors or require an excessive number of collections. Clinical studies with the early acting cytokine, stem cell factor, in combination with G-CSF have demonstrated increased progenitor yields in a range of patients which may translate to clinical benefit in selected situations. In animal models and to a lesser extent in humans, other cytokines such as thrombopoietin and Flt-3 ligand or a number of engineered small molecules with single or dual agonist activity for cytokine receptors (IL-3, Flt-3L, TPO, G-CSF), have also been found to be promising mobilising agents. Further research into the relative importance of cell proliferation, cellular adhesion and the role of accessory cells and other signalling events is leading to an improved understanding of the underlying mechanisms of haemopoietic progenitor mobilisation. Administration of appropriate high-dose chemotherapy followed by re-infusion of haemopoietic progenitor cells capable of long-term reconstitution has long had a place in the treatment of a number of malignant (largely haematological) and non-malignant diseases. For many years these progenitor cells were obtained by direct aspiration of bone marrow under general anaesthetic, hence the term bone marrow transplantation. However, it has also been recognized that haemopoietic stem cells may be recovered from peripheral blood, albeit in low numbers, and also from umbilical cord blood. Further empirical observations showed that the number of haemopoietic progenitors circulating in the blood could be transiently augmented after chemotherapy and/or administration of one or more of a number of cytokines. Refinements to the clinical practice of progenitor mobilisation, collection and enumeration have proved very successful such that in many cases peripheral blood stem cells (PBSC) have largely replaced bone marrow as the preferred source.
Evaluation of Antimicrobial Efficacy and Release Pattern of Tetracycline and Metronidazole Using a Local Delivery System (1998)

The present study compared the effectiveness of two antimicrobials, tetracycline and metronidazole, in reducing subgingival microorganisms in periodontal pockets using an ethyl cellulose strip as the delivery medium. The study involved 30 patients, with a minimum of 3 periodontal pockets with probing depths > 6 mm throughout the oral cavity. Patients were given supragingival scaling and then divided into 5 groups, depending on the length of time the medication was in place. Sites were marked for tetracycline, metronidazole, and placebo. Sites were wiped and isolated, and baseline microbiology samples were taken for Gram staining and culture methods. After treatment, subgingival microbiological samples were taken again. The ethyl cellulose strips were removed and analyzed for any remaining drug. Results showed that tetracycline and metronidazole can both be applied locally to periodontal sites using ethyl cellulose strips and markedly suppress the subgingival bacteria over a period of several days. The tetracycline showed a faster release; however, the metronidazole required a lesser concentration to achieve complete reduction of the subgingival flora.
Ketoacids? Good medicine? (2003)

D-beta-hydroxybutyrate, the principal "ketone" body in starving man, displaces glucose as the predominating fuel for brain, decreasing the need for glucose synthesis in liver (and kidney) and accordingly spares its precursor, muscle-derived amino acids. Thus normal 70 kg. man survives 2-3 months of starvation instead of several weeks, and obese man many months to over a year. Without this metabolic adaptation, H. sapiens could not have evolved such a large brain. Recent studies have shown that D-beta-hydroxybutyrate, the principal "ketone", is not just a fuel, but a "superfuel" more efficiently producing ATP energy than glucose or fatty acid. In a perfused rat heart preparation, it increased contractility and decreased oxygen consumption. It has also protected neuronal cells in tissue culture against exposure to toxins associated with Alzheimer's or Parkinson's. In a rodent model it decreased the death of lung cells induced by hemorrhagic shock. Also, mice exposed to hypoxia survived longer. These and other data suggest a potential use of beta-hydroxybutyrate in a number of medical and non-medical conditions where oxygen supply or substrate utilization may be limited. Efforts are underway to prepare esters of beta-hydroxybutyrate which can be taken orally or parenterally to study its potential therapeutic applications.
The Use of Drugs in Combination for the Treatment of Cancer (1973)

INTEREST in the use of drugs in combination tor the treatment of cancer is not a new phenomenon. It stems from the inability to obtain entirely satisfactory results when available agents are given singly. Theoretical interest in this area can be traced back more than 10 years with the work of Goldin,1 Potter,2 Elion,3 Skipper,4 and Lepage and Sartorelli.5 6 7 The first major clinical effort began in the late 1950's, with the use of drug combinations in the treatment of neoplasms of the testes and other tumors.8 , 9 The current intensity of the interest in this approach derives from two major sources. . . .
Phase II trial of murine monoclonal antibody D612 combined with recombinant human monocyte colony-stimulating factor (rhM-CSF) in patients with metastatic gastrointestinal cancer. (1995)

In a Phase II study, 14 patients with metastatic gastrointestinal cancer received the mAb D612 (40 mg/m2, days 4, 7, and 11) in combination with recombinant human monocyte colony-stimulating factor [(rhM-CSF) 80 micrograms/kg/days 1-14]. The combined treatment was well tolerated and resulted in characteristic biological activity associated with each of the agents. Thus, 10 of 14 patients experienced D612-associated secretory diarrhea, which responded to the prostaglandin inhibitor Indomethacin in 5 of 7 patients. rhM-CSF therapy was associated with peripheral monocytosis (peak absolute monocyte count, 1444 +/- 394/mm3) and thrombocytopenia (nadir count, 78 +/- 10/mm3). Monocyte surface marker analysis revealed a high baseline expression of CD16+ cells in our patient population with an additional increase with rhM-CSF therapy. We observed a correlation between the degree of thrombocytopenia and the pretreatment CD16+ monocyte count. Of the plasma cytokines assayed, serum Neopterin demonstrated the most consistent increase during rhM-CSF therapy. There was a significant difference in the half-life of the first and last dose of D612 (35.8 +/- 2 versus 27 +/- 2.9 h; P < 0.05). Eleven of fourteen patients developed low-moderate levels of anti-D612 antibody. Despite the observed biological activity of both rhM-CSF and D612 and the previously described in vitro synergy, no clinical antitumor responses were observed in this Phase II study.
Enhanced light extraction efficiency of GaN-based LED fabricated by multi-chip array (2015)

In this study, we report the enhanced light extraction efficiency of light emitting diode (LED) devices by employing multi-chip arrayed LED structures. We analyze the optoelectronic property of multi-chip arrayed LED structures with 16, 36 and 64 LED chips in the same 1 × 1 mm2 device as well as 2 × 2 and 3 × 3 mm2 devices. When compared with a conventional large area single-chip LED structure with the same device size, the multi-chip arrayed LED structures generally exhibit enhanced light extraction efficiency and electrical efficiency owing to the reduced current crowding effect. The effect of chip and device size on the LED performance is discussed.
Automatic Choice of Dimensionality for PCA (2000)

A central issue in principal component analysis (PCA) is choosing the number of principal components to be retained. By interpreting PCA as density estimation, this paper shows how to use Bayesian model selection to determine the true dimensionality of the data. The resulting estimate is simple to compute yet guaranteed to pick the correct dimensionality, given enough data. In simulations, it is more accurate than cross-validation and other proposed algorithms, plus it runs much faster. 1 Introduction Principal component analysis (PCA) decomposes high-dimensional data into a low-dimensional subspace component and a noise component. This decomposition is useful for data compression as well as de-noising, making it a common rst step for many data processing tasks. Tipping and Bishop (1997b) have shown that PCA can be interpreted as maximum-likelihood density estimation. This paper extends their work by applying Bayesian model selection to the probabilistic PCA model, providing a simple...
Update onEpidermal Growth Factor ReceptorMutations in Non–Small Cell Lung Cancer (2006)

In 2004, several investigators reported that somatic mutations in the epidermal growth factor receptor gene were associated with clinical responses to erlotinib and gefitinib in patients with non-small cell lung cancer. Since then, multiple groups have examined the biological properties that such mutations confer as well as the clinical relevance of these mutations in patients with non-small cell lung cancer. Although a tremendous amount of knowledge has been gained in the past 2 years, there remain a number of important epidemiologic, biological, and clinical questions.