A structure-based approach for novel immunodiagnostics targeting Trypanosoma cruzi and Schistosoma spp.

The tropical diseases Chagas Disease and Schistosomiasis, caused by the parasites Trypanosoma cruzi and Schistosoma spp, respectively, are often misdiagnosed and if untreated can be fatal. Indeed, their diagnosis presents a current challenge, due to difficulties in recognizing clinical symptoms and the lack of specific and reliable diagnostic tools. Highest prevalence is respectively in Latin America and Central Africa. However, massive human migration from endemic areas and travelling to tropical regions, contribute to the diffusion of these diseases in non-endemic areas, increasing the need of rapid diagnostic tools and prevention strategies. The aim of this project is to develop rapid, peptide-based microarrays that present multiple immunoreactive epitopes predicted from 3D protein structures of antigens from several pathogens, to be applied in point-of-care diagnostic kits for use in the Lombardy area of Italy. This approach showed promising results when applied to antigens from bacterial pathogens, in particular Burkholderia pseudomallei that led to the identification of epitopes with both diagnostic and therapeutic potential. Putative antigens selected from both parasites will be overexpressed, purified and crystallized for 3D structure studies. Based on the determined 3D protein structures, Molecular Dynamics (MD) analyses will be carried out and epitope predictions will be made on output MD structures using the Matrix of Local Coupling Energies method that detects residues located in conformationally dynamic regions of the protein surface. Predicted reactive epitopes will be synthetized as peptides, tested for immunoreactivity against immune sera from infected patients and used for antibody production. Selected immunoreactive synthetic peptides will be immobilised in specific orientations, using click chemistry, on a polymeric coated microarray chip. Sensitivity and specificity of the chip will be evaluated with sera of infected patients

Exploring the Hard X-/soft gamma-ray Continuum Spectra with Laue Lenses

The history of X-ray astronomy has shown that any advancement in our knowledge of the X-ray sky is strictly related to an increase in instrument sensitivity. At energies above 60 keV, there are interesting prospects for greatly improving the limiting sensitivity of the current generation of direct viewing telescopes (with or without coded masks), offered by the use of Laue lenses. We will discuss below the development status of a Hard X-Ray focusing Telescope (HAXTEL) based on Laue lenses with a broad bandpass (from 60 to 600 keV) for the study of the X-ray continuum of celestial sources. We show two examplesof multi-lens configurations with expected sensitivity orders of magnitude better ($\sim 1 \times 10^{-8}$ photons cm$^{-2}$ s$^{-1}$ keV$^{-1}$ at 200 keV) than that achieved so far. With this unprecedented sensitivity, very exciting astrophysical prospects are opened.Comment: 4 pages, 10 figures, to be published in the Proc. of the 39th ESLAB Symosium, 19-21 April 200

Feasibility study of a Laue lens for hard X-rays for space astronomy

We report on the feasibility study of a Laue lens for hard X-rays (>60 keV)based on mosaic crystals, for astrophysical applications. In particular we discuss the scientific motivations, its functioning principle, the procedure followed to select the suitable crystal materials, the criteria adopted to establish crystal dimensions and their distribution on the lens in order to obtain the best lens focusing capabilities, and the criteria for optimizing the lens effective area in a given passband. We also discuss the effects of misalignments of the crystal tiles due to unavoidable mechanical errors in assembling the lens. A software was developed to face all these topics and to evaluate the expected lens performance.Comment: 10 pages, corrected Fig. 1b and Fig. 2, which are wrong in the published version, corrected typo

The GINGER Project and status of the ring-laser of LNGS

A ring-laser attached to the Earth measures the absolute angular velocity of the Earth summed to the relativistic precessions, de Sitter and Lense-Thirring. GINGER (Gyroscopes IN GEneral Relativity) is a project aiming at measuring the LenseThirring effect with a ground based detector; it is based on an array of ring-lasers. Comparing the Earth angular velocity measured by IERS and the measurement done with the GINGER array, the Lense-Thirring effect can be evaluated. Compared to the existing space experiments, GINGER provides a local measurement, not the averaged value and it is unnecessary to model the gravitational field. It is a proposal, but it is not far from being a reality. In fact the GrossRing G of the Geodesy Observatory of Wettzell has a sensitivity very close to the necessary one. G ofWettzell is part of the IERS system which provides the measure of the Length Of the DAY (LOD); G provides information on the fast component of LOD. In the last few years, a roadmap toward GINGER has been outlined. The experiment G-GranSasso, financed by the INFN Commission II, is developing instrumentations and tests along the roadmap of GINGER. In this short paper the main activities of G-GranSasso and some results will be presented. The first results of GINGERino will be reported, GINGERino is the large ring-laser installed inside LNGS and now in the commissioning phase. Ring-lasers provide as well important informations for geophysics, in particular the rotational seismology, which is an emerging field of science. GINGERino is one of the three experiments of common interest between INFN and INGV

Measurement results and improvements on an open EPR system

Electron spin resonance (ESR) is a spectroscopic method that allows to measure stable radicals induced by ionizing radiation. The EPR measurements can help to estimate the dose absorbed by people exposed during a nuclear disaster, detecting the number of radicals induced in their mobile phones due to the exposition [1]. Using conventional closed microwave cavities, the phone display must be fragmented in order to be introduced inside the resonator, becoming no more usable. The aim of this work is to develop a system, compatible with the spectrometer Bruker Elexys E500, able to preserve the sample integrity. The system uses an X-band resonant metallic cavity with a slit, realized on one side, for the leak of the excitation magnetic field and a Helmotz coil pair. The resonator allows measuring a sample lodged outside the cavity, while the coils produce a 100 kHz modulated field that encodes the output signal at a particular frequency and increases the SNR

Standard survey methods for estimating colony losses and explanatory risk factors in Apis mellifera

This chapter addresses survey methodology and questionnaire design for the collection of data pertaining to estimation of honey bee colony loss rates and identification of risk factors for colony loss. Sources of error in surveys are described. Advantages and disadvantages of different random and non-random sampling strategies and different modes of data collection are presented to enable the researcher to make an informed choice. We discuss survey and questionnaire methodology in some detail, for the purpose of raising awareness of issues to be considered during the survey design stage in order to minimise error and bias in the results. Aspects of survey design are illustrated using surveys in Scotland. Part of a standardized questionnaire is given as a further example, developed by the COLOSS working group for Monitoring and Diagnosis. Approaches to data analysis are described, focussing on estimation of loss rates. Dutch monitoring data from 2012 were used for an example of a statistical analysis with the public domain R software. We demonstrate the estimation of the overall proportion of losses and corresponding confidence interval using a quasi-binomial model to account for extra-binomial variation. We also illustrate generalized linear model fitting when incorporating a single risk factor, and derivation of relevant confidence intervals

KRAS status and risk of venous thromboembolic events in patients with metastatic colorectal cancer: a case-control study.

No abstract availabl

Tumor-derived interleukin-10 as a prognostic factor in stage III patients undergoing adjuvant treatment with an autologous melanoma cell vaccine.

OBJECTIVES: Interleukin-10 (IL-10) downregulates T-cell-mediated immune responses. We studied the association between IL-10 production by freshly isolated melanoma cell suspensions in vitro and overall survival in patients undergoing adjuvant treatment with a vaccine prepared from the same autologous melanoma cells modified with a hapten, dinitrophenyl (DNP). METHODS: Forty-four patients with cutaneous melanoma (29 stage III and 15 stage IV) were prospectively evaluated. Tumor cells were extracted from metastatic deposits for production of DNP-modified autologous melanoma cell vaccine. Small aliquots of the melanoma cell suspensions were separated prior to vaccine processing and cultured overnight for IL-10 production. Based on a blind assessment of the distribution of IL-10 levels in the culture supernatants, a cutoff of 200 pg/ml was used to define high versus low IL-10 producers. Cox regression model was used for multivariate analysis. Overall survival was calculated using the Kaplan-Meier method, and survival curves were compared with the log-rank test. RESULTS: Out of 44 patients, 29 were low and 15 were high IL-10 producers. The median OS was significantly worse for high compared with low IL-10 producers (10.5 months vs. 42 months; P = 0.022). In stage III patients, the multivariate hazard ratio for high versus low IL-10 producers was 2.92 (95% CI, 1.04-8.20; P = 0.041). The corresponding hazard ratio in stage IV patients was 0.92 (95% CI, 1.04-8.20; P = 0.888). CONCLUSIONS: High IL-10 production in the tumor microenvironment could be a determinant of clinical outcomes in stage III melanoma patients receiving autologous melanoma cell vaccine