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1
Ellegård, Alvar, Sabina Kielow, Arne Olofsson, Ronald Paul, Ted Tapper, Magnus Ankarsjö, Monica Armini i in. "Reviews and notices". Moderna Språk 93, nr 2 (1.12.1999): 238–55. http://dx.doi.org/10.58221/mosp.v93i2.9703.
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Includes the following reviews:
p. 238. Alvar Ellegård. Svartvik, J., Engleska - öspråk, världsspråk, trendspråk.
p. 239. Sabina Kielow. Ryan, M., Literary Theory. + Widdowson, P., Literature. The New Critical Idiom.
p. 239-243. Arne Olofsson. Olsson, H., Språket - så fungerar det. Lärobok i allmän grammatik och lingvistik.
p. 243-244. Ronald Paul. Ellegård, A., Jesus, One Hundred Years Before Christ: A Study in Creative Mythology.
p. 244-245. Ted Tapper. Löfgre, H. & Shima, A. (eds), After Consensus: Critical Challende and Social Change in America.
p. 245-246. Magnus Ankarsjö. Mahood, M.M., Playing Bit Parts in Shakespeare.
p. 246-247. Monica Armini. Mikalachki, J., The Legacy of Boadicea: Gender and Nation in Early Modern England.
p. 247-249. Esbjörn Nyström. Packalén, S., Im Spiegel der Literatur. Den tyskspråkiga litteraturen under tolv hundra år.
p. 249-251. Christine Pankow/Ingmar Söhrman. Nordstedts bildordbok. Svenska, Engelska, Tyska, Franska.
p. 251-253. Gösta Björn. Kirsch, F. -M., Stille aber ist Mangelware. Deutschland und die Deutschen in schwedischen Schulbüchern für das Fach Deutsch 1970-1995.
p. 253-254. Frank-Michael Kirsch. Müller Waldeck, G. & Ulrich, R. (Hrsg.), Hans Fallada: Sein Leben in Bildern und Briefen.
p. 254-255. Ingmar Söhrman. Nordstedts spanska ordbok. Spansk - svensk, svensk - spansk.
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Jordan, Robert, Deborah Tien, Tove' C. Bolken, Kevin F. Jones, Shanthakumar R. Tyavanagimatt, Josef Strasser, Annie Frimm, Michael L. Corrado, Phoebe G. Strome i Dennis E. Hruby. "Single-Dose Safety and Pharmacokinetics of ST-246, a Novel Orthopoxvirus Egress Inhibitor". Antimicrobial Agents and Chemotherapy 52, nr 5 (3.03.2008): 1721–27. http://dx.doi.org/10.1128/aac.01303-07.
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ABSTRACT ST-246 is a novel, potent orthopoxvirus egress inhibitor that is being developed to treat pathogenic orthopoxvirus infections of humans. This phase I, double-blind, randomized, placebo-controlled single ascending dose study (first time with humans) was conducted to determine the safety, tolerability, and pharmacokinetics of ST-246 in healthy human volunteers. ST-246 was administered in single oral doses of 500, 1,000, and 2,000 mg to fasting healthy volunteers and 1,000 mg to nonfasting healthy volunteers. ST-246 was generally well tolerated with no serious adverse events, and no subject was withdrawn from the study due to ST-246. The most commonly reported drug-related adverse event was neutropenia, which was found, upon further analysis, not to be treatment related. ST-246 was readily absorbed following oral administration with mean times to maximum concentration from 2 h to 3 h. Absorption was greater in nonfasting volunteers than in fasting volunteers. Administration of ST-246 resulted in exposure levels predicted to be sufficient for inhibiting orthopoxvirus replication compared to exposure levels in nonhuman primates in which ST-246 protected animals from lethal orthopoxvirus infection.
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Quenelle, Debra C., R. M. L. Buller, Scott Parker, Kathy A. Keith, Dennis E. Hruby, Robert Jordan i Earl R. Kern. "Efficacy of Delayed Treatment with ST-246 Given Orally against Systemic Orthopoxvirus Infections in Mice". Antimicrobial Agents and Chemotherapy 51, nr 2 (20.11.2006): 689–95. http://dx.doi.org/10.1128/aac.00879-06.
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ABSTRACT ST-246 was evaluated for activity against cowpox virus (CV), vaccinia virus (VV), and ectromelia virus (ECTV) and had an in vitro 50% effective concentration (EC50) of 0.48 μM against CV, 0.05 μM against VV, and 0.07 μM against ECTV. The selectivity indices were >208 and >2,000 for CV and VV, respectively. The in vitro antiviral activity of ST-246 was significantly greater than that of cidofovir, which had an EC50 of 41.1 μM against CV and 29.2 μM against VV, with selectivity indices of >7 and >10, respectively. ST-246 administered once daily by oral gavage to mice infected intranasally with CV beginning 4 h or delayed until 72 h postinoculation was highly effective when given for a 14-day duration using 100, 30, or 10 mg/kg of body weight. When 100 mg/kg of ST-246 was administered to VV-infected mice, a duration of 5 days was sufficient to significantly reduce mortality even when treatment was delayed 24 h postinoculation. Viral replication in liver, spleen, and kidney, but not lung, of CV- or VV-infected mice was reduced by ST-246 compared to levels for vehicle-treated mice. When 100 mg/kg of ST-246 was given once daily to mice infected by the intranasal route with ECTV, treatment for 10 days prevented mortality even when treatment was delayed up to 72 h after viral inoculation. Viral replication in target organs of ECTV-infected mice was also reduced.
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Hosier, I. L., i D. C. Bassett. "A study of the morphologies and growth kinetics of three monodisperse n -alkanes: C 122 H 246 , C 162 H 326 and C 246 H 494". Polymer 41, nr 25 (grudzień 2000): 8801–12. http://dx.doi.org/10.1016/s0032-3861(00)00223-8.
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Yang, Guangjun, Xiaoling Yang i Ping Wang. "Hölder Derivative of the Koch Curve". Journal of Applied Mathematics and Physics 11, nr 01 (2023): 101–14. http://dx.doi.org/10.4236/jamp.2023.111008.
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Finger, Eduardo, Alessandra Finardi de Souza, Thaissa Galante Coimbra i Daniel dos Santos. "Immunodominance of the Sm-p40 antigen contributes to the development of severe schistosomiasis mansoni (99.5)". Journal of Immunology 186, nr 1_Supplement (1.04.2011): 99.5. http://dx.doi.org/10.4049/jimmunol.186.supp.99.5.
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Abstract In murine schistosomiasis, H-2k CBA and C3H mice develop severe CD4 T cell(CD4) mediated liver pathology(LP) and a high Th1/17 response very focused on a single epitope of the parasite egg antigen Sm-p40(p234-246). Low pathology C57BL/6 mice do not recognize this antigen. A possible reason for this result is that p234-246 exacerbated dominance(ED) polarizes the anti-egg response causing severe LP. To test this hypothesis we: a)analyze the LP of SJL mice whose H-2 haplotype also exhibit ED of a single Sm-p40 epitope and b) analyze the LP of CBA mice whose p234-246 ED was neutralized by an epitope cocktail. Methodology:H-2s Sm-p40 restriction pattern was determined with the rankpep software. SJL LP was documented by comparative liver morphometric analysis(LMA) of infected CBA, C57BL/6 and SJL mice euthanized 7 weeks-post-infection(wpi). The effect of p234-246 ED neutralization was studied by LMA of 3 groups of infected CBA mice euthanized at 7wpi. The 1st group was treated with an emulsion of adjuvant and 4 synthetic epitopes designed to compete for I-Ak with an affinity equal or higher than p234-246, the 2nd was treated with adjuvant alone and the 3rd was not treated. Results:LMA shows that SJL mice develop as severe a LP as CBA mice and that p234-246 ED neutralization prevents development of severe LP. Conclusion:These results show that ED may be pathogenic in CD4 mediated diseases and that its neutralization may be an effective therapeutic strategy that deserves exploration.
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Waters, Jennifer C., Rey-Huei Chen, Andrew W. Murray i E. D. Salmon. "Localization of Mad2 to Kinetochores Depends on Microtubule Attachment, Not Tension". Journal of Cell Biology 141, nr 5 (1.06.1998): 1181–91. http://dx.doi.org/10.1083/jcb.141.5.1181.
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A single unattached kinetochore can delay anaphase onset in mitotic tissue culture cells (Rieder, C.L., A. Schultz, R. Cole, G. Sluder. 1994. J. Cell Biol. 127:1301–1310). Kinetochores in vertebrate cells contain multiple binding sites, and tension is generated at kinetochores after attachment to the plus ends of spindle microtubules. Checkpoint component Mad2 localizes selectively to unattached kinetochores (Chen, R.-H., J.C. Waters, E.D. Salmon, and A.W. Murray. 1996. Science. 274:242–246; Li, Y., and R. Benezra. Science. 274: 246–248) and disappears from kinetochores by late metaphase, when chromosomes are properly attached to the spindle. Here we show that Mad2 is lost from PtK1 cell kinetochores as they accumulate microtubules and re-binds previously attached kinetochores after microtubules are depolymerized with nocodazole. We also show that when kinetochore microtubules in metaphase cells are stabilized with taxol, tension at kinetochores is lost. The phosphoepitope 3f3/2, which has been shown to become dephosphorylated in response to tension at the kinetochore (Nicklas, R.B., S.C. Ward, and G.J. Gorbsky. 1995. J. Cell Biol. 130:929–939), is phosphorylated on all 22 kinetochores after tension is reduced with taxol. In contrast, Mad2 only localized to an average of 2.6 out of the 22 kinetochores in taxol-treated PtK1 cells. Therefore, loss of tension at kinetochores occupied by microtubules is insufficient to induce Mad2 to accumulate on kinetochores, whereas unattached kinetochores consistently bind Mad2. We also found that microinjecting antibodies against Mad2 caused cells arrested with taxol to exit mitosis after ∼12 min, while uninjected cells remained in mitosis for at least 6 h, demonstrating that Mad2 is necessary for maintenance of the taxol-induced mitotic arrest. We conclude that kinetochore microtubule attachment stops the Mad2 interactions at kinetochores which are important for inhibiting anaphase onset.
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Próchniak, Joanna, i Renata Płoska. "WIG-20 Warsaw Stock Exchange Companies: Are They Ready for Governance Matters Disclosures Based on EU Sustainable Reporting Standards?" Annales Universitatis Mariae Curie-Skłodowska, sectio H – Oeconomia 56, nr 5 (19.04.2023): 227–46. http://dx.doi.org/10.17951/h.2022.56.5.227-246.
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Theoretical background: In 2022, the European Commission’s intensive efforts to revise and enhance the Non-Financial Reporting Directive (NFRD) from 2014 resulted in the proposal of Corporate Sustainability Reporting Directive (CSRD) and the exposure draft on ESRS EDs (EFRAG Sustainable Reporting Standards Exposure Drafts). The ESRS drafts for public consultation presented the mandatory concepts and principles for sustainability reporting under the CSRD. The implementation of corporate sustainability is closely related to reporting that stimulates robustness of companies’ commitment to sustainability, and sustainable long-term actions taken by companies. Environment is priority, however, having in mind sophisticated environmental performance indicators, it is governance that ensures stakeholders whether the company exercises the sustainable obligations effectively. Purpose of the article: The purpose of the article is to determine EFRAG draft standards compliance with the Warsaw Stock Exchange best practices and Global Reporting Initiative (GRI) standards, and an assessment of WIG-20 reporting practices regarding EFRAG draft standards. The main research question was whether and to what extent WIG-20 companies meet the sustainable reporting exposure drafts on governance matters proposed by EFRAG. Research methods: The study method was desk-based research using the gathered corporate data. The assumptions on the importance of governance matters were supported by VOSviewer analysis of Scopus bibliometric database analysis. Main findings: The results of the study have shown that the scope and level of reported disclosures by WIG-20 companies – that are best performing and positive toward sustainability – is insufficient and reporting practices do not meet proposed EFRAG draft standards. The study contributes to scarce research addressing the sustainability reporting approach. It provides a study of the governance maters regarding draft governance reporting ESRS drafts.
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İşcan, İmdat. "A new improvement of Hölder inequality via isotonic linear functionals". AIMS Mathematics 5, nr 3 (2020): 1720–28. http://dx.doi.org/10.3934/math.2020116.
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Danelli, Anderson Luiz Durante, i Erlei Melo Reis. "Quantification of incubation, latent and infection periods of Phakopsora pachyrhizi in soybean, according to chronological time and degree-days". Summa Phytopathologica 42, nr 1 (marzec 2016): 11–17. http://dx.doi.org/10.1590/0100-5405/1920.
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ABSTRACT In experiments conducted in a growth chamber, the chronological time and the accumulated degree-days were determined for the duration of incubation, latent and infectious periods of Phakopsora pachyrhizi cultivars BRSGO 7560 and BRS 246 RR. Detached soybean leaflets were placed in gerbox-type acrylic boxes and inoculated with 20 x 103 uredospores/mL. The study was conducted at 12-h photoperiod and temperatures of 10ºC, 15ºC, 22ºC, 25ºC and 30°C for 30 days. Lesions and uredia/cm2were evaluated and the number of uredia per lesion was quantified after the beginning of sporulation. The sporulation potential was also quantified for cultivars BRSGO 7560 and BRS 246 RR. The steps of the infection process can be quantified based on both the chronological time and the accumulated heat. The cultivar BRSGO 7560 produced 4,012.8 spores/cm2 and BRS 246 RR, 7,348.4 uredospores/cm2. The largest number of uredia was produced at 25ºC in both cultivars; however, BRS 246 RR presented 372.7 uredia/cm2 and BRSGO 7560, 231.6 uredia/cm2. At 10ºC and 30°C, leaf infection did not occur in both cultivars.
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Jordan, Robert, Jarasvech Chinsangaram, Tove' C. Bolken, Shanthakumar R. Tyavanagimatt, Deborah Tien, Kevin F. Jones, Annie Frimm i in. "Safety and Pharmacokinetics of the Antiorthopoxvirus Compound ST-246 following Repeat Oral Dosing in Healthy Adult Subjects". Antimicrobial Agents and Chemotherapy 54, nr 6 (12.04.2010): 2560–66. http://dx.doi.org/10.1128/aac.01689-09.
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ABSTRACT ST-246, a novel compound that inhibits egress of orthopoxvirus from infected cells, is being evaluated as a treatment for pathogenic orthopoxvirus infections in humans. This phase I, double-blind, randomized, placebo-controlled, escalating multiple-dose study was conducted to determine the safety, tolerability, and pharmacokinetics of ST-246 administered as a single daily oral dose of 250, 400, or 800 mg for 21 days to nonfasting healthy human volunteers. ST-246 appeared to be well tolerated, with no serious adverse events (AEs). Headache, for which one subject in the 800-mg group discontinued the study, was the most commonly reported AE in all treatment groups. The multiple-dose pharmacokinetics of ST-246 was well characterized. The day 21 mean elimination half-lives were calculated at 18.8, 19.8, and 20.7 h for each of the 250-, 400-, and 800-mg/day dose groups, respectively. Steady state was reached by day 6 (within 3 to 5 half-lives), saturable absorption was observed at the 800-mg dose level, and the fraction of parent drug excreted in the urine was very low. Based on these results, administration of 400 mg/day ST-246 can be expected to provide plasma concentrations above the efficacious concentration demonstrated in nonhuman primate models in earlier studies.
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Tarasenko, Anna, i Oleksandr Karelin. "On Invertibility of Functional Operators with Shift in Weighted Hölder Spaces". Advances in Pure Mathematics 04, nr 11 (2014): 595–600. http://dx.doi.org/10.4236/apm.2014.411068.
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Li, Chenyu, i Miao Li. "Hölder Regularity for Abstract Fractional Cauchy Problems with Order in (0,1)". Journal of Applied Mathematics and Physics 06, nr 01 (2018): 310–19. http://dx.doi.org/10.4236/jamp.2018.61030.
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Tedaldi, Chiara. "Iberianism and Crisis: Spain and Portugal at the Turn of the Twentieth Century, Robert P. Newcomb (2018)". International Journal of Iberian Studies 33, nr 1 (1.03.2020): 99–100. http://dx.doi.org/10.1386/ijis_00016_5.
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Review of: Iberianism and Crisis: Spain and Portugal at the Turn of the Twentieth Century, Robert P. Newcomb (2018)Toronto, Buffalo and London: University of Toronto Press, ix + 246 pp.,ISBN 978-1-48750-296-6, h/bk, $60.00
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George, Vic. "A. Evers, H. Nowotny and H. Winterberger (eds), The Changing Face of Welfare, Gower, Farnborough, 1987. 246 pp. £21.50." Journal of Social Policy 17, nr 2 (kwiecień 1988): 259–61. http://dx.doi.org/10.1017/s0047279400016767.
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Moreira, Adônis, Márcia Pereira de Almeida, Danielle Gonçalves Costa i Lucilene Silva Santos. "Acidez potencial pelo método do pH SMP no Estado do Amazonas". Pesquisa Agropecuária Brasileira 39, nr 1 (styczeń 2004): 89–92. http://dx.doi.org/10.1590/s0100-204x2004000100013.
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O objetivo deste trabalho foi definir um modelo matemático que estime o H+Al a partir do pH SMP medido em água e em solução de CaCl2 0,01 mol L-1 nas condições edafoclimáticas locais. Foram utilizadas 246 amostras de solo provenientes de diversas localidades. Mesmo apresentando menor coeficiente da correlação (r = 0,89*), a equação H+Al = 30,646 - 3,848pH SMP obtida em H2O foi mais eficiente que a obtida em solução CaCl2 (H+Al = 30,155 - 3,834pH SMP, r = 0,91*), a qual subestima os valores da acidez potencial.
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Łączek, Marcin. "Elżbieta JENDRYCH, Business English. Wydawnictwo C. H. Beck, Warszawa, 2015, 246 str. , 207–209". Lingwistyka Stosowana 1/2017, nr 21 (27.03.2017): 207–9. http://dx.doi.org/10.32612/uw.20804814.2017.1.pp.207-209.
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Grünenwald, Elisabeth, i Herbert Bauer. "Rezension von: Bauer, Herbert u.a. (Hrsg.), 500 Jahre Hallenchor St. Lorenz in Nürnberg ..." Württembergisch Franken 65 (28.02.2024): 300. http://dx.doi.org/10.53458/wfr.v65i.10637.
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500 Jahre Hallenchor St. Lorenz zu Nürnberg 1477-1977. Hg. im Auftrag des Vereins zur Erhaltung der St. Lorenzkirche und des Vereins für Geschichte der Stadt Nürnberg durch H. Bauer, G. Hirschmann und Gg. Stolz. Nürnberger Forschungen. Band 20. Nürnberg: Verein für Geschichte der Stadt Nürnberg 1977. 246 S., zahlt. Abb.600 Jahre Ostchor St. Sebald - Nürnberg 1379-1979. Hg. von H. Baier im Auftrag des Ev.-Luth. Pfarramtes St. Sebald. Neustadt/Aisch: Schmidt 1979. 221 S., 63 Abb.
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Jones, S. A., i A. J. S. Summerlee. "Effects of chronic infusion of porcine relaxin on oxytocin release in lactating rats". Journal of Endocrinology 114, nr 2 (sierpień 1987): 241–46. http://dx.doi.org/10.1677/joe.0.1140241.
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ABSTRACT The effects of chronic infusion of porcine relaxin on oxytocin release were studied in lactating rats. Infusion of relaxin (4·2 μg/h for either 4 or 6 days) suppressed reflex milk ejection and reduced litter weight gain for 48 h compared with saline-infused controls. After 2 days, neither the rate of growth nor the frequency of milk ejection were significantly different from controls. For 24 h after the infusion of relaxin ended, litters gained weight more quickly than controls but there was no difference seen in the frequency of milk ejection. The effects on oxytocin release of stopping an infusion of relaxin after 3 days were investigated. There was a significant (P <0·01) rise in plasma oxytocin (up to 90 pmol/l) 30 min after the infusion was stopped, followed by a sustained rise in intramammary pressure. Treatment of relaxin-infused rats with naloxone (0·1 mg/kg) when the infusion was halted caused a more rapid release of oxytocin (within 2 min), a greater release of oxytocin (up to 140 pmol/l) and a prolonged rise in intramammary pressure. J. Endocr. (1987) 114, 241–246
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Борисевич, С. С., Я. В. Горохов i С. Г. Архипов. "Место связывания тековиримата – ингибитора мембранного белка p37 ортопоксвирусов". Журнал структурной химии 65, nr 4 (2024): 125428. http://dx.doi.org/10.26902/jsc_id125428.
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Методами молекулярного моделирования (докинг и динамика) определили место связывания тековиримата – ингибитора мембранного белка p37 ортопоксвирусов. Показано, что тековиримат или ST-246 связывается в области фосфолипазного домена H(N)KD, с образованием ряда межмолекулярных контактов с ключевыми а.о. N312 и K314. Данный сайт связывания может рассматриваться, как возможный для локации других малых молекул, со схожим с тековириматом фармакофорным профилем.
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Kreckel, K., P. J. E. Peebles, J. H. van Gorkom, R. van de Weygaert i J. M. van der Hulst. "KK 246: A DWARF GALAXY WITH AN EXTENDED H I DISK IN THE LOCAL VOID". Astronomical Journal 141, nr 6 (12.05.2011): 204. http://dx.doi.org/10.1088/0004-6256/141/6/204.
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Kapoor, Ankita, Arya Mariam Roy, Sanjana Aggarwal, Simrat Gill, Kristopher Attwood, Anthony George, Yagya Ahlawat i in. "From abstract to publication: Factors predictive of publication success in the field of breast and gynecological malignancy." Journal of Clinical Oncology 41, nr 16_suppl (1.06.2023): e23007-e23007. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e23007.
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e23007 Background: Cancer research has rapidly evolved over the last few decades which has led to an improvement in patient care and outcomes. Dissemination of this research presented at meetings is essential to inform clinical practice. However, there continues to be a delay in the publication of data even after successful presentation of research as abstracts. In our study, we aim to determine abstract characteristics associated with successful peer-reviewed publication after presentation at the American Society of Clinical Oncology (ASCO) annual meeting for Breast and Gynecological malignancies. Methods: All oral abstracts (OA) & poster abstracts (PA) presented in the Breast & Gynecologic cancers categories from 2017/2018 ASCO annual meetings were included in the retrospective study. Manuscript publication was confirmed by searching PubMed using a data cut-off of December 2022. Publication characteristics like number of authors, time to publication (in months (mo)), study size, nature of results, impact factor, gender, H-index, citation of first author (FA) & last author (LA), NIH funding of LA were collected. Univariate logistic regression modeling was used to measure the association between publication status and select predictors. Results: 40/50 (80%) OA & 246/527 (46.6%) PA were published in PubMed indexed journals. Mean time to publication for OA was 17.41 mo & for PA was 19.52 mo. Mean IF for published OA was 28 & PA was 9.98. Of presented abstracts, 30/50 (60%) OA & 313/527 (59.39%) PA had positive results. Of the ones published, 23/40 (57.5%) of OA (p=0.72) & 190/246 (77.2%) of PA (p<0.001) had positive findings. 250/527 (49.14%) PA & 17/50 (33.3%) of OA were presented by females. Of the published OA, 15/40 (37.5%) had female FA & 10/40 (25%) female LA. For published PA, FA females were 118/246 (47.9%) while LA females were 86/246 (34.9%). For published PA, median H-index for FA was 33 & LA was 68. 16/40 (40%) LA of published OA & 62/246 (25%) of published PA had NIH funding. Conclusions: Our study reveals that poster abstracts with positive findings are more likely to be published, implying publication bias in research. In addition, there is also higher likelihood of publication if last author is NIH funded. Our study highlights the need to address these factors to maximize the chances of publication of impactful research. [Table: see text]
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Mohell, Nina, Charlotta Liljebris, Jessica Alfredsson, Ylva Lindman, Maria Uustalu, Thomas Uhlin, Mats R. H. Linderholm i Klas G. Wiman. "Preclinical Efficacy and Toxicology Studies of APR-246, a Novel Anticancer Compound Currently In Clinical Trials for Refractory Hematological Malignancies and Prostate Cancer". Blood 116, nr 21 (19.11.2010): 1806. http://dx.doi.org/10.1182/blood.v116.21.1806.1806.
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Abstract Abstract 1806 The tumor suppressor protein p53 is a transcription factor involved in cell cycle arrest, senescence and apoptosis. The p53 gene is frequently mutated in cancer, and cancer cells carrying defects in p53 are generally more resistant to conventional chemotherapy. Thus, restoration of wild type function of p53 is a promising novel strategy for cancer therapy. APR-246 belongs to a new class of small molecules (quinuclidinones) that reactivates non-functional p53 by promoting its correct folding and triggering apoptosis (Lambert et al. Cancer Cell 15, 2009). The lead compound of APR-246, PRIMA-1 (p53 Reactivation and Induction of Massive Apoptosis) was identified by a cellular screen of a NCI (National Cancer Institute) library, and an optimization program led to the discovery of the analog APR-246 (PRIMA-1MET). In various in vitro,ex vivo andin vivo cancer models, APR-246 has shown good antitumor activity. It reduces cell viability and/or induces apoptosis in a large number of human cancer cell lines with different p53 status, including leukemia, lymphoma and myeloma cell lines (Mohell et al. Blood 114, 2009). Ex vivo efficacy of APR-246 alone and in combination with conventional chemotherapeutic drugs has been shown in primary cells from patients with acute myeloid leukemia (AML) (Jonsson-Videsater et al. Blood 114, 2009). Ex vivo efficacy of APR-246 has also been shown in primary cells from patients with chronic lymphocytic leukemia (CLL). APR-246 was 4–8 fold more potent in killing malignant than normal lymphocytes, whereas common cytostatics often have negative ratio (Mohell et al. Blood 114, 2009). In vivo efficacy of APR-246/PRIMA-1 has been demonstrated in xenograft studies using many solid tumor cell lines (Mohell et al. Blood 114, 2009). Here we present results from studies with APR-246 using in vivo systemic and metastasic xenograft model with the human AML primary cell line AML-PS. This model was established by Giovazzi et al. (Int. J. Cancer 61, 1995) and is considered as a predictive in vivo model for human AML. In addition, some key results from preclinical safety and toxicology studies are reported. Briefly, SCID (severe combined immunodeficiency) mice were inoculated i.v. with 5×106 human AML-PS primary cells. Three days after inoculation treatment with i.v. injections of APR-246 (200 and 300 mg/kg), twice daily for 10 days, was initiated. Mice were monitored daily for health status and mortality. Blood samples were collected for determination of the percentage of circulating human leukemia cells by FACS analysis. Human leukemic cells were detected using a fluorescent antibody against the major histocompatibility complex (HLA). In parallel, pharmacokinetic experiments to measure the concentration of APR-246 in the blood were performed. We found that APR-246 had a statistically significant antitumor effect by decreasing the percentage of circulating human AML-PS cells and increasing the survival time of the mice (P=0.0024, n=10). A good correlation between increase in survival time and decrease in circulating tumor cells in the blood was observed. Further in vivo efficacy studies using various treatment schedules and combinations with conventional cytostatics are ongoing. APR-246 was also investigated in pivotal toxicology studies using single and repeat-dose regimen. In dogs, APR-246 was well tolerated when administered as 2 h infusion with NOAEL (no observed adverse effect level) of 200 mg/kg/day (4000 mg/m2/day). In both dogs and mice, Cmax levels less than 100 μg/ml did not induce any toxicity, regardless of the administration protocol. No systemic target organ toxicity was observed in mice or dogs, including blood and bone-marrow parameters. In conclusion, APR-246 has in various efficacy models demonstrated significant antitumor activity and a unique pharmacological profile. In preclinical safety/toxicity studies no toxicity at predicted therapeutic plasma concentrations was observed. Thus, APR-246 appears to be a promising novel anticancer compound to treat patients resistant to common chemotherapy. Currently, APR-246 is investigated in a dose escalating Phase I/IIa First-in-Man study for refractory hematological malignancies and prostate cancer. The Phase II Proof of Concept study is planned to start in 2011. Disclosures: Mohell: Aprea AB: Employment. Liljebris:Aprea AB: Employment. Alfredsson:Aprea AB: Employment. Lindman:Aprea AB: Employment. Uustalu:Aprea AB: Employment. Uhlin:Aprea AB: Employment. Linderholm:Aprea AB: Consultancy. Wiman:Aprea AB: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.
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Kimura, Mitsutaka, Mitsuhiro Imaizumi i Toshio Nakagawa. "Replication Policy of Real-Time Distributed System for Cloud Computing". International Journal of Reliability, Quality and Safety Engineering 22, nr 05 (październik 2015): 1550024. http://dx.doi.org/10.1142/s0218539315500242.
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Recently, cloud computing has been widely used for the purpose of protecting client data on the Internet [A. Weiss, Computing in the clouds, netWorker11 (2007) 16–25; M. Armbrust et al., Above the clouds: A Berkeley view of cloud computing, Technical Report UCV/EECS-2009-28, University of California at Berkeley (2009)]. But when a client receives network service, response time may be slow because the data center is located in a remote place. In order to solve the problem, real-time distributed systems for cloud computing has been proposed [M. Okuno, D. Ito, H. Miyamoto, H. Aoki, Y. Tsushima and T. Yazaki, A study on distributed information and communication processing architecture for next generation cloud system, IEICE Tech. Report109(A48) (2010) 241–246; M. Okuno, S. Tsutsumi and T. Yazaki, A study of high available distributed network processing technique for next generation cloud system, IEICE Tech. Report111(8) (2011) 25–30; S. Yamada, J. Marukawa, D. Ishii, S. Okamoto and N. Yamanaka, A study of parallel transmission technique with GMPLS in intelligent cloud network, IEICE Tech. Report109(455) (2010) 51–56]. The cloud computing system consists of some intelligent nodes as well as a data center. The data center manages all client data. The intelligent node provides client service near clients. It enables to provide client service at short response time [M. Okuno, D. Ito, H. Miyamoto, H. Aoki, Y. Tsushima and T. Yazaki, A study on distributed information and communication processing architecture for next generation cloud system, IEICE Tech. Report109(448) (2010) 241–246]. We considered the reliability model of distributed information processing for cloud computing, derived cost effectiveness and discussed the optimal replication interval to minimize it [M. Kimura, M. Imaizumi and T. Nakagawa, Reliability modeling of distributed information processing for cloud computing, in Proc. 20th ISSAT Int. Conf. Reliability and Quality in Design (2014), pp. 183–187]. Authors had dealt with the server system with one failure mode. In this paper, we consider the reliability model of a real-time distributed system with n intelligent nodes and formulate a stochastic model of the server system with n intelligent nodes for changing the other normal intelligent node at failure. We derive the expected numbers of the replication and of updating the client data. Further, we derive the expected cost and discuss an optimal replication interval to minimize it. Next, we derive the cost effectiveness and discuss an optimal number of intelligent nodes to minimize it.
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Larcombe, Alexander N., Philip C. Withers i Stewart C. Nicol. "Thermoregulatory, metabolic and ventilatory physiology of the eastern barred bandicoot (Perameles gunnii)". Australian Journal of Zoology 54, nr 1 (2006): 9. http://dx.doi.org/10.1071/zo05071.
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Thermoregulatory, metabolic and ventilatory parameters measured for the Tasmanian eastern barred bandicoot (Perameles gunnii) in thermoneutrality (ambient temperature = 30°C) were: body temperature 35.1°C, basal metabolic rate 0.55 mL O2 g–1 h–1, wet thermal conductance 2.2 mL O2 g–1 h–1 °C–1, dry thermal conductance 1.4 J g–1 h–1 °C–1, ventilatory frequency 24.8 breaths min–1, tidal volume 9.9 mL, minute volume of 246 mL min–1, and oxygen extraction efficiency 22.2%. These physiological characteristics are consistent with a cool/wet distribution, e.g. high basal metabolic rate (3.33 mL O2 g–0.75 h–1) for thermogenesis, low thermal conductance (0.92 J g–1 h–1 °C–1 at 10°C) for heat retention and intolerance of high ambient temperatures (≥35°C) with panting, hyperthermia and high total evaporative water loss (16.9 mg H2O g–1 h–1).
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Delorenzo Neto, A. "A Codificação Municipal de Florianópolis". Revista do Serviço Público 72, nr 02 (14.02.2020): 178–86. http://dx.doi.org/10.21874/rsp.v72i02.4409.
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A mais complexa codificação municipal vigente no País é a de Florianópolis,aprovada psla Lei n.° 246 de 15 de novembro de 1955, louvável iniciativado Prefeito O s m a r C u n h a . Com efeito, nêsse texto redobramos nossos esforçosem apurar as ncrrnas e estender ao máximo o campo da competência própriado Município. Seguimos rigorosamente nossa metodologia, que comporta asseguintes fases:
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Fung, Y. C., i S. Q. Liu. "Changes of zero-stress state of rat pulmonary arteries in hypoxic hypertension". Journal of Applied Physiology 70, nr 6 (1.06.1991): 2455–70. http://dx.doi.org/10.1152/jappl.1991.70.6.2455.
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Zero-stress state of the main pulmonary arteries, from the main trunk to a vessel with a lumen diameter approximately 60 microns, was determined in 25 normal control and 38 hypoxic pulmonary hypertensive rats. Pulmonary hypertension was induced by placing the rats in a hypoxic chamber with 10% O2-90% N2 at atmospheric pressure. The zero-stress state of each vessel was obtained by first cutting the vessel transversely into a series of rings and then cutting each ring radially, whereupon the ring opened into a sector, which is characterized by an opening angle defined as the angle subtended between two lines originating from the midpoint of the inner wall (endothelium) to the tips of the inner wall. Whereas the pulmonary blood pressure increased monotonically during the development of pulmonary hypertension, the opening angle followed a different course; e.g., the values (means +/- SD) of the opening angle at the pulmonary trunk at times 0 (control) and 2, 12, 28, 96, 144, 240, 480, and 720 h after exposure to hypoxia are, respectively, 294 +/- 30 degrees, 378 +/- 24 degrees, 385 +/- 12 degrees, 374 +/- 11 degrees, 246 +/- 63 degrees, 267 +/- 49 degrees, 193 +/- 19 degrees, 195 +/- 83 degrees, and 239 +/- 38 degrees. Trends at other places on the artery are similar, but the magnitudes differ. In this period of time, intimal edema and thickening were found. The intima media thickened rapidly from 48 to 240 h and then more slowly from 240 to 720 h. Adventitia thickened later; its thickness exceeded that of the intima media at approximately 96 h. Thus the changes of zero-stress state of the pulmonary arteries are seen to be related to the nonuniform remodeling of the vessel wall as revealed by the edema, blebs, and thickening of different layers.
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Ni, Jiahao, i Shan Zhang. "Uniform H&#246;lder Bounds for Competition Systems with Strong Interaction on a Subdomain". Journal of Applied Mathematics and Physics 11, nr 06 (2023): 1525–40. http://dx.doi.org/10.4236/jamp.2023.116100.
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Hernandez, Hector J., i Miguel J. Stadecker. "Elucidation and Role of Critical Residues of Immunodominant Peptide Associated with T Cell-Mediated Parasitic Disease". Journal of Immunology 163, nr 7 (1.10.1999): 3877–82. http://dx.doi.org/10.4049/jimmunol.163.7.3877.
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Abstract Granulomatous inflammation in schistosomiasis is strictly dependent on CD4+ Th lymphocytes sensitized to egg Ags, but its intensity is genetically regulated. C3H and CBA (H-2k) are strains of mice that develop large granulomas; they also strongly respond to the major egg Ag Sm-p40. We now show that the immunodominant epitope recognized by CD4+ Th cells from infected H-2k mice is confined to 13-mer peptide 234–246 (PKSDNQIKAVPAS), which elicits an I-Ak-restricted Th1-type response. Using a panel of alanine-monosubstituted peptides, we identified Asp237 as the main contact residue with I-Ak. On the other hand, three TCR contact residues were essential to stimulate epitope-specific T cell hybridomas: for two hybridomas these were Asn238, Gln239, and Lys241; and for one, Asn238, Lys241, and Pro244. In one instance, alanine substitution for Gln239 generated an antagonist that blocked subsequent stimulation with wild-type peptide. Most importantly, replacement of Asn238, Gln239, or Lys241 caused a profound loss of polyclonal CD4+ T cell reactivity from schistosome-infected mice. This study identifies the critical residues of immunodominant peptide 234–246 involved in the T cell response against the Sm-p40 egg Ag and suggests that suitable altered peptides may be capable of precipitating its down-regulation.
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Fujii, Nobuharu, Kellie V. Rosinski, Paulo V. Campregher i Edus H. Warren. "Identification of Novel MHC Class II-Restricted Male-Specific mHAg Encoded bySMCY(JARID1D).." Blood 114, nr 22 (20.11.2009): 1344. http://dx.doi.org/10.1182/blood.v114.22.1344.1344.
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Abstract Abstract 1344 Poster Board I-366 Male recipients of female hematopoietic cell grafts, when compared with all other donor/recipient gender combinations, have an increased risk for both acute and chronic GVHD, but also have a significantly decreased risk of posttransplant relapse. F→M HCT is also characterized at the cellular level by donor (female) T cell responses against male-specific minor histocompatibility (H-Y) antigens, which can contribute to both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) activity. SMCY is a Y-chromosome gene that has previously been shown to encode at least two distinct MHC class I-restricted H-Y antigens presented by HLA-A*0201 and HLA-B*0702, respectively. Also, association between CD8+ T cell responses specific for the SMCY311-319 FIDSYICQV epitope and GVHD or GVL has been reported. A CD8+ FIDSYICQV-specific T cell clone was also reported to induce histological signs of GVHD reaction in an in vitro skin-explant assay. To date, however, only two MHC class I-restricted, and no MHC class II-restricted, H-Y antigens encoded by SMCY have been characterized. Given the large size of the SMCY and the homologous SMCX proteins and the fact that they are only 85% identical at the amino acid sequence level, we hypothesized that SMCY encodes other MHC class I- and class II-restricted H-Y antigens, and that T cell responses against these epitopes may likewise contribute to GVHD and GVL activity after F→M HCT. Arrays of pentadecapeptides with eleven-residue overlap were designed to tile regions of the SMCY protein that are non-identical to the corresponding regions of its X chromosome-encoded homologue SMCX, and then used to generate SMCY-specific T cell lines recognizing novel SMCY-encoded MHC class I- and class II-restricted H-Y antigens. Peripheral blood mononuclear cells (PBMC) were obtained on posttransplant day +126 from a 46 year-old male patient with monosomy 7 AML who had received a hematopoietic cell graft from his MHC-identical sister, and were stimulated in vitro with dendritic cells derived from his pretransplant PBMC that had been pulsed with the SMCY pentadecapeptides. After three stimulations, a SMCY peptide-specific CD4+ T cell line as well as a SMCY311-319 (FIDSYICQV)-specific CD8+ T cell line were obtained. After cloning by limiting dilution, we further characterized the SMCY-specific CD4+ T cell clone, 13H3. The 13H3 T cell clone recognizes the SMCY232-246 15-mer peptide, ELKKLQIYGPGPKMM, presented by HLA-DRB1*1501, and has a CD3+, CD4+, CD8−, CD45RA−, CD45RO+ surface phenotype. The cytokine release profile of this clone when assessed with SMCY232-246-loaded donor-derived EBV-LCL, as measured by the Luminex assay, is characterized mainly by Th1 cytokines (IFN-g and IL-2), but the clone also produced low to moderate levels of the Th2 cytokines IL-4, IL-10, and TGF-β. A minigene encoding SMCY232-246 was recognized by the 13H3 clone in a HLA-DRB1*1501-dependent fashion when transfected into COS-7 cells, but a minigene encoding the homologous SMCX-derived ELKKLQIYGAGPKMM peptide was not recognized, demonstrating that the clone is SMCY-specific. The 13H3 clone recognized 3 of 5 HLA-DRB1*1501+ male primary leukemia cells, but did not recognize either of 2 HLA-DRB1*1501− male or either of 2 HLA-DRB1*1501+ female primary leukemia cells. These results suggest that CD4+ T cell responses against the SMCY232-246 epitope could potentially contribute to GVL activity after F→M HCT. A SMCY232-246/HLA-DRB1*1501 tetramer has been constructed which specifically marks the 13H3 T cell clone, and future studies will use this reagent to determine whether CD4+ T cells specific for this epitope can be detected directly ex vivo in posttransplant blood samples from HLA-DRB1*1501+ F→M HCT recipients. Disclosures No relevant conflicts of interest to declare.
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Glöckner, Andreas. "Johann Sebastian Bachs Aufführungen zeitgenössischer Passionsmusiken". Bach-Jahrbuch 63 (22.03.2018): 75–119. http://dx.doi.org/10.13141/bjb.v19772029.
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Es handelt sich um die erhaltenen Manuskripte der Matthäuspassion von Reinhard Keiser, der Lukaspassion eines unbekannten Komponisten (BWV 246), der Händelschen Passionsvertonung nach einem Text von B. H. Brockes, eines Pasticcios mit Musik von Keiser und Händel und eines weiteren Pasticcios. Die Manuskripte werden im Hinblick auf die Frage nach Bachs Veränderungen im musikalischen Text betrachtet. Verschiedene Umstände deuten auf Bachs zunehmende Nutzung von Passionsvertonungen anderer Komponisten ab etwa 1740 hin. (Übertragung des englischen Resümees am Ende des Bandes)
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Walters, E. G., D. G. Proctor, G. H. Elder i G. Walters. "Urinary Excretion of HMMA in Children". Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 26, nr 1 (styczeń 1989): 44–48. http://dx.doi.org/10.1177/000456328902600106.
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In two centres urinary excretion of HMMA was measured in a total of 359 children, aged from birth to 17 years, who were suspected of having a neuroblastoma; the diagnosis was subsequently confirmed in 39. Measurements were made on 24 h urine samples in 246 children, and on random samples in a further 113. The urinary excretion of HMMA relative to creatinine declined progressively with increasing age. After the age of four years the rate of decline was such that some age groups could be combined for statistical analysis. The range of values for each group was similar whether 24 h or random urine collections were used. It is concluded that the latter are adequate for the initial assessment of HMMA excretion.
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Donath, Matthias. "Familie von Felgenhauer in Riesa und Hirschstein". Sächsische Heimatblätter 65, nr 3 (1.07.2019): 243–46. http://dx.doi.org/10.52410/shb.bd.65.2019.h.3.s.243-246.
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Demir, Salih, Galina Selivanova, Eugen Tausch, Lisa Wiesmüller, Stephan Stilgenbauer, Geertruy Te Kronnie, Klaus-Michael Debatin i Lüder Hinrich Meyer. "Targeting Mutant p53 in Pediatric Acute Lymphoblastic Leukemia". Blood 126, nr 23 (3.12.2015): 903. http://dx.doi.org/10.1182/blood.v126.23.903.903.
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Abstract Mutations of the tumor suppressor gene TP53 have been described to be associated with aggressive disease and inferior prognosis in different types of cancer, including hematological malignancies. In acute lymphoblastic leukemia (ALL), TP53 alterations are infrequently found at diagnosis but have recently been described in about 12% of patients at relapse. This suggests an association with therapy resistance in high risk/relapsed ALL and patients with TP53 mutated ALL have in fact an inferior outcome. Small molecule compounds targeting mutated TP53 such as APR-246, initially described as PRIMA-1MET (p53-dependent reactivation and induction of massive apoptosis) leading to apoptosis induction have shown activity in several types of malignancies with mutated TP53. In ALL, however, mutant TP53 has so far not been addressed as a target for therapeutic intervention. In this study, we investigated a large cohort of patient-derived pediatric B cell precursor (BCP)-ALL primograft samples to identify cases with mutated TP53. Further, we analyzed the effects of APR-246 and evaluated its activity on BCP-ALL cell lines and primografts with mutated (mut) orwild type (wt) TP53. Altogether, 62 BCP-ALL primograft samples established from patients at diagnosis (n=53) or relapse (n=9) by transplantation of primary ALL cells onto NOD/SCID mice were screened for TP53 mutations by denaturating high-performance liquid chromatography (dHPLC) followed by Sanger sequencing of exons 4 to 10 to confirm detected mutations. We identified 4 cases with TP53 mut, 3 obtained from diagnosis (5.6%) and one at relapse (11.1%), corresponding to frequencies described in clinical studies. Mutated cases were further analyzed by fluorescence in situ hybridization (FISH), revealing a 17p deletion in one TP53 mut sample. Similarly, we analyzed 6 BCP-ALL cell lines and identified 2 TP53 mut and 4 TP53 wt lines. Exposure of BCP-ALL primograft (TP53 mut n=4, TP53 wt n=4) and cell line (TP53 mut n=2, TP53 wt n=4) samples to the DNA damaging agent doxorubicin showed, as expected, resistance of TP53 mut leukemia cells for cell death induction, reflected by significantly higher half maximal inhibitory concentrations (IC50; TP53 mut 49 and 143 ng/ml, TP53 wt mean 12 ng/ml) and lower induction of cell death (TP53 mut 16 to 23%, TP53 wt 10 to 60%) in TP53 mut ALL, corroborating the tumor-suppressive function of p53 in ALL. We then investigated the sensitivity of BCP-ALL cell lines for cell death induction by APR-246 (kindly provided by Aprea, Stockholm, Sweden). We observed high sensitivity for APR-246 in TP53 mut (IC50: 5 µM for both cell lines) as compared to TP53 wt ALL (mean IC50: 58 µM). DNA fragmentation and Annexin-V/propidium-iodide (PI) positivity revealed apoptosis as mechanism of APR-246 mediated cell death. Reactive oxygen species (ROS) have recently been described to mediate APR-246 induced cell death in multiple myeloma cells. Therefore, we investigated ROS levels by detection of oxidation-specific fluorescence of dichlorodihydrofluorescein diacetate (DCFDA) in ALL cells. Interestingly, ROS quenching by N-acetyl cysteine abolished induction of cell death in TP53 mut but not TP53 wt ALL cells indicating ROS as a mediator of APR-246 induced cell death in TP53 mut ALL. Furthermore, we addressed p53 activation in response to APR-246 by assessing phosphorylation of p53 (p53pSer15) using phosphoflow cytometry. Most interestingly, APR-246 led to 6-fold increased p53pSer15 levels in TP53 mut compared to no activation in TP53 wt leukemia cells, indicating restoration of p53function upon APR-246treatment in BCP-ALL. Based on these findings, we addressed the effectivity of APR-246on primary, patient-derived primografts and compared sensitivities for cell death induction in TP53 mut (n=4) and TP53 wt (n=4) samples. Importantly, the pattern of responsiveness of TP53 mut ALL was also identified in TP53 mut patient-derived ALL samples with induction of significantly higher cell death rates in TP53 mut ALL (TP53 mut 48%, TP53 wt 18%, 5 µM APR-246, 24 h). Taken together, we showed that TP53 mut BCP-ALL can be targeted by APR-246 leading to re-activation of p53, induction of ROS dependent apoptosis and effective leukemia cell killing. Thus, targeting and re-activation of mutated p53 provides a promising novel strategy for therapeutic intervention in this high-risk subtype of BCP-ALL. Disclosures Selivanova: Aprea: Patents & Royalties: APR-246. Tausch:Gilead: Other: Travel support. Stilgenbauer:Gilead: Honoraria, Research Funding.
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Chernonosov, Alexander A., Galina A. Oleinik i Vladimir V. Koval. "Application of Parallel Reaction Monitoring to the Development and Validation of a Quantitative Assay for ST-246 in Human Plasma". International Journal of Molecular Sciences 23, nr 14 (21.07.2022): 8021. http://dx.doi.org/10.3390/ijms23148021.
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In this work, we developed and validated a robust and sensitive method of liquid chromatography with high-resolution mass spectrometry in parallel reaction monitoring (PRM) mode for ST-246 (tecovirimat) quantification in human blood plasma. The method was compared with the multiple reaction monitoring (MRM) technique and showed better selectivity and similar sensitivity in a wider concentration range (10–5000 ng/mL). Within this range, intra- and interday variability of precision and accuracy were within acceptable ranges in accordance with the European Medicines Agency guidelines, and recovery was 87.9–100.6%. Samples were stable at 4 °C within 48 h and at −20 °C up to 3 months. The recovery and matrix effects in the proposed HRMS method were about 5% higher than those reported for the MRM method, but the PRM method showed better accuracy with comparable precision. It was found that the ST-246 concentration shown by the PRM method is approximately 24% higher than the output of the MRM one. Nonetheless, the high selectivity with similar sensitivity, as compared with traditional MRM methods, makes the proposed approach attractive for research and clinical use.
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Leonard, Charles T., Daniel Y. Sandholdt, James A. McMillan i Susan Queen. "Short- and Long-Latency Contributions to Reciprocal Inhibition During Various Levels of Muscle Contraction of Individuals With Cerebral Palsy". Journal of Child Neurology 21, nr 3 (marzec 2006): 240–47. http://dx.doi.org/10.2310/7010.2006.00068.
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Deficits in reciprocal inhibition likely contribute to excessive antagonist muscle cocontraction during voluntary movements of individuals with cerebral palsy. This study examined neural contributions to reciprocal inhibition of the soleus motoneurons of individuals with spastic, diplegic cerebral palsy and nondisabled individuals during various levels of voluntary tibialis anterior contraction. A condition-test H-reflex paradigm examined short- and long-latency contributions to reciprocal inhibition of soleus neural pools during changing levels of voluntary tibialis anterior contraction. Electrically induced short- and long-latency inhibition was similar between healthy, neurologically intact control subjects and subjects with cerebral palsy during rest. With increasing levels of tibialis anterior contraction, control subjects experienced increasing levels of soleus motoneuron inhibition, especially of long-latency inhibitory responses. In contrast, there was no evidence of modulation of short- or long-latency inhibition with increasing levels of tibialis anterior contraction among subjects with cerebral palsy. Deficits in long-latency (presynaptic) inhibition appear to contribute prominently to voluntary movement impairment of individuals with cerebral palsy. ( J Child Neurol 2006;21:240—246).
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Ewing, Laura E., Charles M. Skinner, Charles M. Quick, Stefanie Kennon-McGill, Mitchell R. McGill, Larry A. Walker, Mahmoud A. ElSohly, Bill J. Gurley i Igor Koturbash. "Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model". Molecules 24, nr 9 (30.04.2019): 1694. http://dx.doi.org/10.3390/molecules24091694.
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The goal of this study was to investigate Cannabidiol (CBD) hepatotoxicity in 8-week-old male B6C3F1 mice. Animals were gavaged with either 0, 246, 738, or 2460 mg/kg of CBD (acute toxicity, 24 h) or with daily doses of 0, 61.5, 184.5, or 615 mg/kg for 10 days (sub-acute toxicity). These doses were the allometrically scaled mouse equivalent doses (MED) of the maximum recommended human maintenance dose of CBD in EPIDIOLEX® (20 mg/kg). In the acute study, significant increases in liver-to-body weight (LBW) ratios, plasma ALT, AST, and total bilirubin were observed for the 2460 mg/kg dose. In the sub-acute study, 75% of mice gavaged with 615 mg/kg developed a moribund condition between days three and four. As in the acute phase, 615 mg/kg CBD increased LBW ratios, ALT, AST, and total bilirubin. Hepatotoxicity gene expression arrays revealed that CBD differentially regulated more than 50 genes, many of which were linked to oxidative stress responses, lipid metabolism pathways and drug metabolizing enzymes. In conclusion, CBD exhibited clear signs of hepatotoxicity, possibly of a cholestatic nature. The involvement of numerous pathways associated with lipid and xenobiotic metabolism raises serious concerns about potential drug interactions as well as the safety of CBD.
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Bauer, Joachim, G. G. Gottfries, Hans Förstl i H. H. Kornhuber. "Critical Comments on “Propionibacterium acnes in the cortex of patients with Alzheimer's disease” by H. H. Kornhuber (Eur Arch Psychiatry Clin Neurosci, 1996, 246:108–109)". European Archives of Psychiatry and Clinical Neuroscience 246, nr 4 (czerwiec 1996): 224–26. http://dx.doi.org/10.1007/bf02188958.
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Beura, D., D. Acharya, P. Singh i S. Acharya. "Högbomite Associated with Vanadium bearing Titaniferous Magnetite of Mafic-Ultramafic Suite of Moulabhanj Igneous Complex, Orissa, India". Journal of Minerals and Materials Characterization and Engineering 08, nr 09 (2009): 745–53. http://dx.doi.org/10.4236/jmmce.2009.89064.
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Ahmed, T., T. Syriste, J. Lucio, W. Abraham, M. Robinson i J. D'Brot. "Inhibition of antigen-induced airway and cutaneous responses by heparin: a pharmacodynamic study". Journal of Applied Physiology 74, nr 4 (1.04.1993): 1492–98. http://dx.doi.org/10.1152/jappl.1993.74.4.1492.
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We have previously shown that heparin attenuates the acute bronchoconstrictor response and immediate cutaneous reaction (ICR) to antigen in allergic sheep. In the present investigation, we studied the pharmacodynamics of the antiallergic action of heparin. Specific lung resistance (sRL) was measured in eight sheep, allergic to Ascaris suum antigen, before and 5 min after inhalation challenge with the antigen. On different experiment days, antigen challenge was repeated after pretreatment with 1) aerosol heparin (1,000 U/kg) administered < or = 20 min, 6 h, 12 h, and 24 h and 2) intravenous heparin (1,000 U/kg) administered < or = 20 min, 1 h, 6 h, and 12 h before antigen challenge. sRL increased by 374 +/- 116% (SE) above baseline with antigen alone. Both aerosol and intravenous heparin attenuated the antigen effects on sRL in a time-dependent fashion. Prolonging the lag time between pretreatment and antigen challenge decreased the inhibitory effect of aerosol heparin; delta sRL was 31 +/- 29, 99 +/- 38, 142 +/- 40, and 306 +/- 60% for < or = 20-min, 6-h, 12-h, and 24-h pretreatment protocols, respectively. In contrast, prolonging the lag time increased the inhibitory effect of intravenous heparin: delta sRL was 246 +/- 64, 66 +/- 26, and 76 +/- 32% for < or = 20 min, 1 h, and 6 h, respectively. In seven additional sheep pretreatment with intravenous heparin (1,000 U/kg) attenuated the ICR also in a time-dependent manner; the inhibitory effect of heparin on ICR to antigen was enhanced 60% by increasing the heparin pretreatment interval from 20 to 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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Peng, Yifan, Jifeng Tang i Jiaqin Xie. "Transcriptomic Analysis of the Brown Planthopper, Nilaparvata lugens, at Different Stages after Metarhizium anisopliae Challenge". Insects 11, nr 2 (24.02.2020): 139. http://dx.doi.org/10.3390/insects11020139.
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Nilaparvata lugens is one of the major pests of rice and results in substantial yield loss every year. Our previous study found that the entomopathogenic fungus Metarhizium anisopliae showed effective potential for controlling this pest. However, the mechanisms underlying M. anisopliae infection of N. lugens are not well known. In the present study, we further examined the transcriptome of N. lugens at 4 h, 8 h, 16 h, and 24 h after M. anisopliae infection by Illumina deep sequencing. In total, 174.17 Gb of data was collected after sequencing, from which 23,398 unigenes were annotated by various databases, including 3694 newly annotated genes. The results showed that there were 246 vs 75, 275 vs 586, 378 vs 1055, and 638 vs 182 up- and downregulated differentially expressed genes (DEGs) at 4 h, 8 h, 16 h, and 24 h after M. anisopliae infection, respectively. The biological functions and associated metabolic processes of these genes were determined with the Clusters of Orthologous Groups (COG), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The DEGs data were verified using RT-qPCR. These results indicated that the DEGs during the initial fungal infection appropriately reflected the time course of the response to the fungal infection. Taken together, the results of this study provide new insights into the molecular mechanisms underlying the insect host response to fungal infection, especially during the initial stage of infection, and may improve the potential control strategies for N. lugens.
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Elliott, Jessie A., Neil G. Docherty, Jacqueline Haag, Hans-Georg Eckhardt, Narayanasamy Ravi, John V. Reynolds i Carel W. le Roux. "Attenuation of satiety gut hormones increases appetitive behavior after curative esophagectomy for esophageal cancer". American Journal of Clinical Nutrition 109, nr 2 (1.02.2019): 335–44. http://dx.doi.org/10.1093/ajcn/nqy324.
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ABSTRACT Background Reduced appetite and weight loss are common after esophagectomy (ES), and this cohort demonstrates an exaggerated postprandial satiety gut hormone response. Satiety gut hormones modulate food reward, resulting in reduced energy intake. Objectives This study aimed to determine the effect of satiety gut hormone modulation by measuring the effect of the somatostatin analog octreotide on appetitive behavior among patients after ES. Methods In this randomized, double-blind, placebo-controlled crossover study, patients ≥1 y after ES and matched controls received either 1 mL 0.9% saline or 1 mL (100 μg) octreotide subcutaneously before completing a progressive ratio task. A measure of appetitive behavior, this task requires subjects to undertake progressively increasing amounts of work to obtain a sweet-fat reinforcer; the final completed increment (breakpoint) represents reinforcer reward value. Separate cohorts were studied in the fasted or 1-h postprandial states. Results Thirty-six subjects (ES, n = 18; matched controls, n = 18) were studied. The ES subjects were 2.5 ± 0.3 y postoperation and had a weight loss of 14.6% ± 2.6% and elevated postprandial glucagon-like peptide 1 compared with controls (49.2 ± 13.4 compared with 20.2 ± 2.3 pM; P = 0.04). Octreotide did not alter the breakpoint among ES or control subjects when tested in a fasting condition (ES: 980 ± 371 compared with 1700 ± 584 clicks; P = 0.16; controls: 1056 ± 274 compared with 1124 ± 273 clicks; P = 0.81). When tested 1 h postprandially, octreotide was associated with an increased breakpoint compared with placebo among ES subjects (322 ± 143 compared with 246 ± 149 clicks; P = 0.04) but not controls (248 ± 119 compared with 247 ± 120 clicks; P = 0.97). Conclusions Attenuation of the exaggerated postprandial satiety gut hormone response is associated with increased appetitive behavior toward a sweet-fat stimulus among patients post-ES. Suppression of satiety gut hormones may be a novel target to increase appetite, food intake, and body weight among patients after ES. This study was registered at clinicaltrials.gov as NCT02381249.
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Kujbida, Marcin, Agnieszka Wróblewska, Grzegorz Lewandowski, Piotr Miądlicki i Beata Michalkiewicz. "W-SBA-15 as an Effective Catalyst for the Epoxidation of 1,5,9-Cyclododecatriene". Molecules 27, nr 24 (10.12.2022): 8769. http://dx.doi.org/10.3390/molecules27248769.
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The results of a study on the epoxidation of 1,5,9-cyclododecatriene (CDT) on a W-SBA-15 catalyst using the batch and half-periodic methods are presented. During this study, the activity of the W-SBA-15 catalyst was compared to that of the Ti-SBA-15 catalyst, and the W-SBA-15 catalyst was found to be about 20 times more active than the Ti-SBA-15 catalyst. The highest CDT conversion so far, amounting to 86 mol%, was obtained after carrying out the 4 h epoxidation process. Conducting the studied process using the semi-batch method did not result in the significant improvement in value functions describing this process (CDT conversion and selectivity of CDT transformation to ECDD), but the fastest H2O2 dosing rate (246 µL/h) allowed us to obtain 9 mol% higher CDT conversion in comparison to the batch method.
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Sarwar, Huma, Meshal M. Meshal M Naeem, Sumaiya Shabbir, Sania Riaz, Hasan Afaq i Juzer Shabbir. "Effect of Hydrogen Peroxide on Cyclic Fatigue Resistance of NiTi Endodontic Files". Journal of the Pakistan Dental Association 29, nr 04 (11.11.2020): 246–48. http://dx.doi.org/10.25301/jpda.294.246.
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OBJECTIVE: To investigate the effect of nickel titanium rotary endodontic file immersion in hydrogen peroxide on cyclic fatigue resistance. METHODOLOGY: Twenty Six Protaper Universal (Dentsply Maillerfier) F1 files were randomly divided into two experimental groups. In Group I, Protaper universal variable taper F1 files were immersed in normal saline where as in Group II, the files were soaked in hydrogen peroxide (6% w/v) for 2 hours at 37°C. Cyclic fatigue of each file was checked by recording the number of rotations required to break a file in a 90°curve with a 5 mm radius. For statistical analysis of data, Two-way ANOVA was applied. A p value of <0.05 was considered significant. RESULT: Out of Twenty Six, Six files fractured spontaneously after immersion in hydrogen peroxide. Twenty files were subjected to fracture resistance testing. Statistically significant difference in cyclic fatigue resistace between the two groups was found (p=0.002). The files soaked in Group II required less revolutions to fracture than the ones immersed Group I. CONCLUSION: The immersion of NiTi endodontic files in hydrogen peroxide significantly reduces cyclic fatigue resistance. Therefore, immersion of the NiTi endodontic files in hydrogen peroxide solution for removal of clogged debris should be discouraged. KEYWORDS: Cyclic fatigue, Endodontic instruments, Hydrogen peroxide, NiTi HOW TO CITE: Sarwar H, Naeem MM, Shabbir S, Riaz S, Afaq H, Shabbir J. Effect of hydrogen peroxide on cyclic fatigue resistance of NiTi endodontic files. J Pak Dent Assoc 2020;29(4):246-248.
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Burt, D. S., K. H. Mills, J. J. Skehel i D. B. Thomas. "Diversity of the class II (I-Ak/I-Ek)-restricted T cell repertoire for influenza hemagglutinin and antigenic drift. Six nonoverlapping epitopes on the HA1 subunit are defined by synthetic peptides." Journal of Experimental Medicine 170, nr 2 (1.08.1989): 383–97. http://dx.doi.org/10.1084/jem.170.2.383.
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H-2k-restricted T cell clones derived from CBA mice infected with X31 (H3N2) influenza virus, were shown to recognize distinct, nonoverlapping sequences within the HA1 subunit of the viral hemagglutinin (HA) using synthetic peptides. Three I-Ak-restricted T cell sequences were identified within HA1 68-83, 120-139, and 269-288, and two recognition sites presented in the context of the I-Ek molecule were mapped to HA1 sequences 226-245 and 246-265. T cell clones specific for these regions of HA1 demonstrated varying abilities to differentiate between natural variant viruses that had accumulated substitutions within their HA molecules as a result of antigenic drift. Clones that recognized sequences HA1 226-245 and HA1 246-265 failed to discriminate between natural variants and focused on conserved sequences within these epitopes. A majority of T cell clones were sensitive to amino acid substitutions that have featured in antigenic drift occurring within three major antigenic sites of the HA1 subunit; substitutions at HA1 residues 78 (V)/83(K) and 275(D)/278(I) within the HA1 subunit of mutant viruses correlated with a 75% reduction in the proliferative response for T cell clones specific for sequences HA1 68-83 and HA1 269-288, respectively. Furthermore, a clone that recognized HA1 120-139 was nonresponsive to a mutant virus HK/71, implicating amino acids at HA1 position 129(G) and/or 132(Q) within this sequence as crucial for recognition. Our data, together with the previous finding that sequence HA1 53-63 is also a major I-Ak-restricted T cell recognition site, demonstrate a level of diversity in the T cell recognition of influenza HA, within a single mouse haplotype hitherto unrecognized, and imply that the T cell repertoire diversity against foreign antigens may be greater than previously assumed. Furthermore, the frequency at which HA-specific T cells have been identified that focus on amino acids within the HA1 subunit of HA also featuring in antigenic drift, suggests that a failure of MHC class II-restricted T cells to recognize specific epitopes within mutant HA molecules may contribute significantly to the capacity of variant influenza viruses to evade immune recognition.
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Jafarzadeh, Hamid, Zahed Mohammadi, Sousan Shalavi, Rasoul Sahebalam i Jun-Ichiro Kinoshita. "Additive and reducing Effects between Calcium Hydroxide and Current Irrigation Solutions". Journal of Contemporary Dental Practice 18, nr 3 (2017): 246–49. http://dx.doi.org/10.5005/jp-journals-10024-2025.
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ABSTRACT Introduction Microorganisms should be considered to have the major role in starting and perpetuation of pulpo-periapical diseases. Using intracanal medicaments is necessary to gain a bacteria-free environment in the canal system. Calcium hydroxide (abbreviated as Ca(OH)2), which is the most commonly used medicament in endodontic therapy, has been shown to be effective against primary sources of infection; however, its effectiveness against some microorganisms, such as Candida albicans and Enterococcus faecalis has not been proved. On the other hand, sodium hypochlorite (NaOCl), chlorhexidine (CHX), and iodine potassium iodide (IKI) have been shown to be the potent medicaments against these microorganisms. Because of this fact, combination of Ca(OH)2 and some irrigants of the root canal has been suggested as potential intracanal medicaments. The aim of this literature review is to identify and address the efficacy of Ca(OH)2 in combined with some of these irrigating solutions. How to cite this article Mohammadi Z, Jafarzadeh H, Shalavi S, Sahebalam R, Kinoshita JI. Additive and reducing Effects between Calcium Hydroxide and Current Irrigation Solutions. J Contemp Dent Pract 2017;18(3):246-249.
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VanHook, Annalisa M. "Papers of note in Science". Science Signaling 9, nr 423 (12.04.2016): ec87-ec87. http://dx.doi.org/10.1126/scisignal.aaf8405.
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CANCERMacrophages block tumors' spreadLymph node macrophages provide a physical barrier against tumor spread.F. Pucci, C. Garris, C. P. Lai, A. Newton, C. Pfirschke, C. Engblom, D. Alvarez, M. Sprachman, C. Evavold, A. Magnuson, U. H. von Andrian, K. Glatz, X. O. Breakefield, T. R. Mempel, R. Weissleder, M. J. Pittet, SCS macrophages suppress melanoma by restricting tumor-derived vesicle–B cell interactions. Science352, 242–246 (2016). [Abstract]CANCER BIOLOGYOncogene control of antitumor immunityAberrant activation of the MYC gene helps tumor cells evade the immune response.S. C. Casey, L. Tong, Y. Li, R. Do, S. Walz, K. N. Fitzgerald, A. M. Gouw, V. Baylot, I. Gütgemann, M. Eilers, D. W. Felsher, MYC regulates the antitumor immune response through CD47 and PD-L1. Science352, 227–231 (2016). [Abstract]TRANSCRIPTIONHow bacteria switch between tracksA powerful technique is described for discovering riboswitches and attenuators that respond to previously unknown ligands.D. Dar, M. Shamir, J. R. Mellin, M. Koutero, N. Stern-Ginossar, P. Cossart, R. Sorek, Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria. Science352, aad9822 (2016). [Abstract]M. O. A. Sommer, B. Suess, (Meta-)genome mining for new ribo-regulators. Science352, 144–145 (2016). [Abstract]
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Jacobson, J. M., M. Davidian, P. M. Rainey, R. Hafner, R. H. Raasch i B. J. Luft. "Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii." Antimicrobial Agents and Chemotherapy 40, nr 6 (czerwiec 1996): 1360–65. http://dx.doi.org/10.1128/aac.40.6.1360.
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Pyrimethamine pharmacokinetics were studied in 11 human immunodeficiency virus (HIV)-positive patients who were seropositive for exposure to Toxoplasma gondii and were taking zidovudine (AIDS Clinical Trials Group Protocol 102). Pyrimethamine was administered at 50 mg daily for 3 weeks to achieve steady state, and pharmacokinetic profiles were determined after administration of the last dose. Noncompartmental and compartmental analyses were performed. Population pharmacokinetic analysis assuming a one-compartment model yielded the following estimates: area under the 24-h concentration-time curve, 42.7 +/- 12.3 micrograms.h/ml; halflife, 139 +/- 34 h; clearance, 1.28 +/- 0.41 liters/h; volume of distribution, 246 +/- 641; and absorption rate constant, 1.5 +/- 1.3 liters/h. These values are similar to those seen in subjects without HIV infection. Pyrimethamine pharmacokinetics did not differ significantly in those subjects who were intravenous drug users. Adverse effects were noted in 73% of those initially enrolled in this study, leading to discontinuation for 38%. No association was noted between pyrimethamine levels and the incidence of adverse events. No significant differences were seen in zidovudine pharmacokinetic parameters obtained from studies performed before and during treatment with pyrimethamine. In summary, pyrimethamine exhibited pharmacokinetics in HIV-infected patients that were similar to those in non-HIV-infected subjects and it did not alter the pharmacokinetics of zidovudine in these patients.
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Karelin, Oleksandr, i Anna Tarasenko. "Application of Interpolation Inequalities to the Study of Operators with Linear Fractional Endpoint Singularities in Weighted Hölder Spaces". Applied Mathematics 05, nr 17 (2014): 2779–85. http://dx.doi.org/10.4236/am.2014.517266.
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McMaster, P. "Experimental and clinical liver transplantation. R. Engemann and H. Hamelmann. 246 × 170 mm. Pp. 254 + xii. Illustrated. 1991. Amsterdam: Elsevier". British Journal of Surgery 79, nr 7 (lipiec 1992): 719. http://dx.doi.org/10.1002/bjs.1800790764.
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