239. Ocena efektu przeciwnowotworowego genetycznie modyfikowanej szczepionki komórkowej w mysim modelu raka nerki

CelGenetycznie modyfikowane szczepionki komórkowe (GMTV) mają za zadanie indukcję efektywnej odpowiedzi przeciwnowotworowej. Postanowiliśmy ocenić efekt protekcyjny dwóch różnych GMTV w mysim modelu raka jasnokomórkowego nerki, oraz rolę komórek dendrytycznych w fazie indukcji przeciwnowotworowej odpowiedzi komórkowej.MetodyPrzy wykorzystaniu wektorów retrowirusowych DCCMV-IRES-Neo-H-6 oraz DCCMV-IRES-Neo-IL-6 wprowadzono do komórek mysiego raka jasnokomórkowego (RenCa) skonstruowano dwa rodzaje GMTV: (i) Komórki RenCa wykazujące ekspresję genu Interleukiny-6, (ii) komórki RenCa wykazujące ekspresję genu Hyper-lnterleukiny-6 (sztuczna cytokina będąca białkiem fuzyjnym składającym się z IL-6 powiązanej sztucznym linkerem z agonistycznym rozpuszczalnym receptorem) W celu oceny efektu protekcyjnego GMTV, myszy Balb/c w wieku 8–12 tygodni (8 osobników w jednej grupie eksperymentalnej) immunizowano podając podskórnie w lewe udo, 1×10^6 naświetlonych (80 Gy) komórek (RenCa w/t, RenCa-IL-6, Renca-H6). Po 14 dniach myszom podawano podskórnie w prawe udo wyjściowe komórki RenCa w/t w ilości 5×10^5. Następnie oceniano dynamikę pojawiania się guzów oraz kinetykę ich wzrostu. W celu oceny mechanizmów indukcji odpowiedzi immunologicznej postanowiono ocenić in situ wpływ poszczególnych rodzajów GMTV na komórki dendrytyczne. Myszy Balb/c otrzymywały w okolicy śródbrzusza, podskórnie 2×10^6 napromienionych (80 Gy) komórek Renca w/t, Renca-IL-6, Renca H-6 zawieszonych w Matrigelu™. Po 7 dniach przy pomocy cytometru przepływowego analizowano komórki naciekające Matrigel.Wyniki i podsumowanieImmunizacja myszy komórkami RenCa-H6 okazała się najbardziej efektywna w porównaniu do komórek RenCa w/t i RenCa-IL-6. Jakkolwiek nie przeciwdziałała wzrostowi guzów. Aktywowane komórki DC naciekały najsilniej komórki RenCa-H6. Efekt protekcyjny wyraźnie korelował z ilością aktywowanych komórek DC naciekających miejsce podania GMTV. Intensywna infiltracja miejsca podania GMTV przez komórki DC o wysokim poziomie aktywacji wskazuje na silną role Hyper-Interleukiny-6 w procesie indukcji funkcjonalnej przeciwnowotworowej odpowiedzi immunologicznej

Active Amplification of the Terrestrial Albedo to Mitigate Climate Change: An Exploratory Study

This study explores the potential to enhance the reflectance of solar insolation by the human settlement and grassland components of the Earth's terrestrial surface as a climate change mitigation measure. Preliminary estimates derived using a static radiative transfer model indicate that such efforts could amplify the planetary albedo enough to offset the current global annual average level of radiative forcing caused by anthropogenic greenhouse gases by as much as 30 percent or 0.76 W/m2. Terrestrial albedo amplification may thus extend, by about 25 years, the time available to advance the development and use of low-emission energy conversion technologies which ultimately remain essential to mitigate long-term climate change. However, additional study is needed to confirm the estimates reported here and to assess the economic and environmental impacts of active land-surface albedo amplification as a climate change mitigation measure.Comment: 21 pages, 3 figures. In press with Mitigation and Adaptation Strategies for Global Change, Springer, N

‘Ethnic group’, the state and the politics of representation

The assertion, even if only by implication, that ‘ethnic group’ categories represent ‘real’ tangible entities, indeed identities, is commonplace not only in the realms of political and policy discourse but also amongst contemporary social scientists. This paper, following Brubaker (2002), questions this position in a number of key respects: of these three issues will dominate the discussion that follows. First, there is an interrogation of the proposition that those to whom the categories/labels refer constitute sociologically meaningful ‘groups’ as distinct from (mere) human collectivities. Secondly, there is the question of how these categories emerge, i.e. exactly what series of events, negotiations and contestations lie behind their construction and social acceptance. Thirdly, and as a corollary to the latter point, we explore the process of reification that leads to these categories being seen to represent ‘real things in the world’ (ibid.)

Chronic probiotic supplementation with or without glutamine does not influence the eHsp72 response to a multi-day ultra-endurance exercise event

Probiotic and glutamine supplementation increases tissue Hsp72, but their influence on extracellular Hsp72 (eHsp72) has not been investigated. The aim of this study was to investigate the effect of chronic probiotic supplementation, with or without glutamine, on eHsp72 concentration before and after an ultramarathon. Thirty-two participants were split into three independent groups, where they ingested probiotic capsules (PRO, n = 11), probiotic + glutamine powder (PGLn, n = 10) or no supplementation (CON, n = 11), over a 12-week period prior to commencement of the Marathon des Sables (MDS). eHsp72 concentration in the plasma was measured at baseline, 7 days pre-race, 6-8 hours post-race, and 7 days post-race. The MDS increased eHsp72 concentrations by 124% (F1,3 = 22.716, p 0.05). In conclusion, the MDS caused a substantial increase in eHsp72 concentration indicating high levels of systemic stress. However, chronic PRO or PGLn supplementation did not effect eHsp72 compared to control pre- or post-MDS. Given the role of eHsp72 in immune activation, the commercially available supplements used in this study are unlikely to influence this cascade

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

OBJECTIVE: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. METHODS: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. RESULTS: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. CONCLUSION: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration

Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (p_T), elliptic flow, two-particle correlations, non-statistical fluctuations, and suppression of particle production at high p_T. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted to Nuclear Physics A as a regular article; v3 has minor changes in response to referee comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results