Charles University in Prague

About: Charles University in Prague is a education organization based out in Prague, Czechia. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 32392 authors who have published 74435 publications receiving 1804208 citations.

Human Tumor Cells Killed by Anthracyclines Induce a Tumor-Specific Immune Response

Abstract: Immunogenic cell death is characterized by the early surface exposure of chaperones includingcalreticulin and HSPs, which affect dendritic cell (DC) maturation and the uptake and presentation oftumor antigens. It has also been shown that it is characterized by the late release of high mobility group box1 (HMGB1), which acts through Toll-like receptor 4 (TLR4) and augments the presentation of antigens fromdying tumor cells to DCs. Most of the data on immunogenic tumor cell death were obtained using mousemodels. In this study, we investigated the capacity of clinically used chemotherapeutics to induceimmunogenic cell death in human tumor cell lines and primary tumor cells. We found that onlyanthracyclines induced a rapid translocation of calreticulin, HSP70, and HSP90 to the cell surface andthe release of HMGB1 12 hours after the treatment. The interaction of immature DCs with immunogenictumor cells led to an increased tumor cell uptake and induces moderate phenotypic maturation of DCs.Killed tumor cell–loaded DCs efficiently stimulated tumor-specific IFN-g–producing T cells. DCs pulsedwith killed immunogenic tumor cells also induced significantly lower numbers of regulatory T cells thanthose pulsed with nonimmunogenic tumor cells. These data indicate that human prostate cancer, ovariancancer, and acute lymphoblastic leukemia cells share the key features of immunogenic cell death with micetumor cells. These data also identify anthracyclinesas anticancer drugs capable of inducing immunogeniccell death in sensitive human tumor cells. Cancer Res; 71(14); 4821–33. 2011 AACR.

Dijet cross sections and parton densities in diffractive DIS at HERA

Abstract: Differential dijet cross sections in diffractive deep-inelastic scattering are measured with the H1 detector at HERA using an integrated luminosity of 51.5 pb−1. The selected events are of the type ep → eXY , where the system X contains at least two jets and is well separated in rapidity from the low mass proton dissociation system Y . The dijet data are compared with QCD predictions at next-to-leading order based on diffractive parton distribution functions previously extracted from measurements of inclusive diffractive deepinelastic scattering. The prediction describes the dijet data well at low and intermediate zIP (the fraction of the momentum of the diffractive exchange carried by the parton entering the hard interaction) where the gluon density is well determined from the inclusive diffractive data, supporting QCD factorisation. A new set of diffractive parton distribution functions is obtained through a simultaneous fit to the diffractive inclusive and dijet cross sections. This allows for a precise determination of both the diffractive quark and gluon distributions in the range 0.05 < zIP < 0.9. In particular, the precision on the gluon density at high momentum fractions is improved compared to previous extractions.

Nomenclature of the micas

Abstract: End-members and species defined with permissible ranges of composition are presented for the true micas, the brittle micas, and the interlayer-deficient micas. The determination of the crystallochemical formula for different available chemical data is outlined, and a system of modifiers and suffixes is given to allow the expression of unusual chemical substitutions or polytypic stacking arrangements. Tables of mica synonyms, varieties, ill-defined materials, and a list of names formerly or erroneously used for micas are presented. The Mica Subcommittee was appointed by the Commission on New Minerals and Mineral Names of the International Mineralogical Association. The definitions and recommendations presented were approved by the Commission.

Measurement of Higgs boson production and properties in the WW decay channel with leptonic final states

Abstract: A search for the standard model Higgs boson decaying to a W-boson pair at the LHC is reported. The event sample corresponds to an integrated luminosity of 4.9 fb−1 and 19.4 fb−1 collected with the CMS detector in pp collisions at s√ = 7 and 8 TeV, respectively. The Higgs boson candidates are selected in events with two or three charged leptons. An excess of events above background is observed, consistent with the expectation from the standard model Higgs boson with a mass of around 125 GeV. The probability to observe an excess equal or larger than the one seen, under the background-only hypothesis, corresponds to a significance of 4.3 standard deviations for m H = 125.6 GeV. The observed signal cross section times the branching fraction to WW for m H = 125.6 GeV is 0.72+0.20−0.18 times the standard model expectation. The spin-parity J P = 0+ hypothesis is favored against a narrow resonance with J P = 2+ or J P = 0− that decays to a W-boson pair. This result provides strong evidence for a Higgs-like boson decaying to a W-boson pair.

The incidence and significance of anti-natalizumab antibodies: Results from AFFIRM and SENTINEL

Abstract: Objective: To determine the incidence and clinical effects of antibodies that develop during treatment with natalizumab. Methods: In two randomized, double-blind, placebo-controlled studies (natalizumab safety and efficacy in relapsing remitting multiple sclerosis [MS, AFFIRM] and safety and efficacy of natalizumab in combination with interferon β-1a [INFβ1a] in patients with relapsing remitting MS [SENTINEL]) of patients with relapsing multiple sclerosis, blood samples were obtained at baseline and every 12 weeks to determine the presence of antibodies against natalizumab. Antibodies to natalizumab were measured using an ELISA. Patients were categorized as “transiently positive” if they had detectable antibodies (≥0.5 μg/mL) at a single time point or “persistently positive” if they had antibodies at two or more time points ≥6 weeks apart. Results: In the AFFIRM study, antibodies were detected in 57 of 625 (9%) of natalizumab-treated patients: Twenty (3%) were transiently positive and 37 (6%) were persistently positive. Persistently positive patients showed a loss of clinical efficacy as measured by disability progression ( p ≤ 0.05), relapse rate ( p = 0.009), and MRI ( p ≤ 0.05) compared with antibody-negative patients. In transiently positive patients, full efficacy was achieved after approximately 6 months of treatment, the time when patients were becoming antibody negative. The incidence of infusion-related adverse events was significantly higher in persistently positive patients. Results of SENTINEL were similar to AFFIRM, except with regard to sustained disability progression; differences between persistently positive and antibody-negative patients were not statistically significant. Conclusions: The incidence of persistent antibody positivity associated with natalizumab is 6%. Reduced clinical efficacy is apparent in persistently positive patients. Patients with a suboptimal clinical response or persistent infusion-related adverse events should be considered for antibody testing. GLOSSARY: BLQ = below the limit of quantification; EDSS = Expanded Disability Status Scale; Gd+ = gadolinium enhancing; IFNβ1a = interferon β-1a; MS = multiple sclerosis; MSFC = multiple sclerosis functional composite; OD = optical density.