RLumCarlo:Simulating Cold Light using Monte Carlo Methods

International audienceAbstract The luminescence phenomena of insulators and semiconductors (e.g., natural minerals such as quartz) have various application domains. For instance, Earth Sciences and archaeology exploit luminescence as a dating method. Herein, we present the R package RLumCarlo implementing sets of luminescence models to be simulated with Monte Carlo (MC) methods. MC methods make a powerful ally to all kinds of simulation attempts involving stochastic processes. Luminescence production is such a stochastic process in the form of charge (electron-hole pairs) interaction within insulators and semiconductors. To simulate luminescence-signal curves, we distribute single and independent MC processes to virtual MC clusters. RLumCarlo comes with a modularized design and consistent user interface: (1) C++ functions represent the modeling core and implement models for specific stimulations modes. (2) R functions give access to combinations of models and stimulation modes, start the simulation and render terminal and graphical feedback. The combination of MC clusters supports the simulation of complex luminescence phenomena

On the stochastic uncertainties of thermally and optically stimulated luminescence signals:A Monte Carlo approach

International audiencePhenomenological models are frequently used to analyze experimental signals in thermally and optically stimulated luminescence experiments. Typically, these models consist of systems of differential equations describing various electronic transitions. An alternative to the differential equation approach is the use of Monte Carlo (MC) methods, which also allow an estimation of the theoretical stochastic uncertainty of the intensity of the lumi- nescence signal. By running and averaging several MC variants, these stochastic uncertainties are estimated in this paper for various luminescence models. In the case of first-order kinetics processes, the MC results compare well with previously published analytical results for the coefficient of variation (CV) in stochastic linear pure death processes. By contrast, no analytical results are available for the more general one trap one recombination center model (OTOR), and MC is the only method available for estimating the stochastic uncertainties. In this paper the CV coefficients are simulated for three commonly used experimental stimulation modes, namely thermally stimulated luminescence (TL), continuous-wave optically stimulated luminescence (CW-OSL) and linearly modulated OSL (LM-OSL). The results of the simulations show that CW-OSL signals have the smallest CV values among the three stimulation modes, and therefore these signals are least likely to exhibit stochastic variations. The stochastic uncertainties in these phenomenological models are discussed in the context of single grain luminescence experiments and nanodosimetric materials, in which one deals with small numbers of charge carriers

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

RLumCarlo: Monte-Carlo Methods for Simulating Luminescence Phenomena

A collection of functions to simulate luminescence production in dosimetric materials using Monte Carlo methods. Implemented are models for delocalised transitions (e.g., Chen and McKeever (1997) ), localised transitions (e.g., Pagonis et al. (2019) ) and tunnelling transitions (Jain et al. (2012) and Pagonis et al. (2019) ). Supported stimulation methods are thermal luminescence (TL), continuous-wave optically stimulated luminescence (CW-OSL), linearly-modulated optically stimulated luminescence (LM-OSL), linearly-modulated infrared stimulated luminescence (LM-IRSL), and isothermal luminescence (ITL or ISO-TL)

RLumCarlo: Monte-Carlo Methods for Simulating Luminescence Phenomena

A collection of functions to simulate luminescence production i

RLumCarlo:Monte-Carlo Methods for Simulating Luminescence Phenomena

A collection of functions to simulate luminescence production in dosimetric materials using Monte Carlo methods. Implemented are models for delocalised transitions (e.g., Chen and McKeever (1997) ), localised transitions (e.g., Pagonis et al. (2019) ) and tunnelling transitions (Jain et al. (2012) and Pagonis et al. (2019) ). Supported stimulation methods are thermal luminescence (TL), continuous-wave optically stimulated luminescence (CW-OSL), linearly-modulated optically stimulated luminescence (LM-OSL), linearly-modulated infrared stimulated luminescence (LM-IRSL), and isothermal luminescence (ITL or ISO-TL)

Oral focal mucinosis of the tongue: A rare clinical entity?

Oral focal mucinosis (OFM) is regarded as a very rare clinical entity with only 62 cases previously reported in the literature. The majority of these cases have been present on gingiva and only 3 cases have been diagnosed on the tongue. The clinical appearance of OFM is relatively non-specific and resembles other and more prevalent conditions like fibroepithelial hyperplasia or other reactive mucosal lesions. The present case report describes OFM in the tongue in an 88-year-old woman. The report addresses the diagnostic considerations of OFM, but also if the lesion is really as rare as the literature indicates