A glance into mthfr deficiency at a molecular level

MTHFR deficiency still deserves an investigation to associate the phenotype to protein structure variations. To this aim, considering the MTHFR wild type protein structure, with a catalytic and a regulatory domain and taking advantage of state‐of‐the‐art computational tools, we explore the properties of 72 missense variations known to be disease associated. By computing the thermodynamic ΔΔG change according to a consensus method that we recently introduced, we find that 61% of the disease‐related variations destabilize the protein, are present both in the catalytic and regulatory domain and correspond to known biochemical deficiencies. The propensity of solvent accessible residues to be involved in protein‐protein interaction sites indicates that most of the interacting residues are located in the regulatory domain, and that only three of them, located at the interface of the functional protein homodimer, are both disease‐related and destabilizing. Finally, we compute the protein architecture with Hidden Markov Models, one from Pfam for the catalytic domain and the second computed in house for the regulatory domain. We show that patterns of disease‐associated, physicochemical variation types, both in the catalytic and regulatory domains, are unique for the MTHFR deficiency when mapped into the protein architecture

Inferring DNA sequences from mechanical unzipping: an ideal-case study

We introduce and test a method to predict the sequence of DNA molecules from in silico unzipping experiments. The method is based on Bayesian inference and on the Viterbi decoding algorithm. The probability of misprediction decreases exponentially with the number of unzippings, with a decay rate depending on the applied force and the sequence content.Comment: Source as TeX file with ps figure

Inferring DNA sequences from mechanical unzipping data: the large-bandwidth case

The complementary strands of DNA molecules can be separated when stretched apart by a force; the unzipping signal is correlated to the base content of the sequence but is affected by thermal and instrumental noise. We consider here the ideal case where opening events are known to a very good time resolution (very large bandwidth), and study how the sequence can be reconstructed from the unzipping data. Our approach relies on the use of statistical Bayesian inference and of Viterbi decoding algorithm. Performances are studied numerically on Monte Carlo generated data, and analytically. We show how multiple unzippings of the same molecule may be exploited to improve the quality of the prediction, and calculate analytically the number of required unzippings as a function of the bandwidth, the sequence content, the elasticity parameters of the unzipped strands

Parylene C-based, breathable tattoo electrode for high-quality biopotential measurements

A breathable tattoo electrode for bio-potential recording based on a Parylene C nanofilm is presented in this study. The proposed approach allows for the fabrication of micro-perforated epidermal submicrometer-thick electrodes that conjugate the unobtrusiveness of Parylene C nanofilms and the very important feature of breathability. The electrodes were fully validated for electrocardiography (ECG) measurements showing performance comparable to that of conventional disposable gelled Ag/AgCl electrodes, with no visible negative effect on the skin even many hours after their application. This result introduces interesting perspectives in the field of epidermal electronics, particularly in applications where critical on-body measurements are involved

The X-Gamma Imaging Spectrometer (XGIS) onboard THESEUS

A compact and modular X and gamma-ray imaging spectrometer (XGIS) has been designed as one of the instruments foreseen on-board the THESEUS mission proposed in response to the ESA M5 call. The experiment envisages the use of CsI scintillator bars read out at both ends by single-cell 25 mm 2 Silicon Drift Detectors. Events absorbed in the Silicon layer (lower energy X rays) and events absorbed in the scintillator crystal (higher energy X rays and Gamma-rays) are discriminated using the on-board electronics. A coded mask provides imaging capabilities at low energies, thus allowing a compact and sensitive instrument in a wide energy band (~2 keV up to ~20 MeV). The instrument design, expected performance and the characterization performed on a series of laboratory prototypes are discussed.Comment: To be published in the Proceedings of the THESEUS Workshop 2017 (http://www.isdc.unige.ch/theseus/workshop2017.html), Journal of the Italian Astronomical Society (Mem.SAIt), Editors L. Amati, E. Bozzo, M. Della Valle, D. Gotz, P. O'Brien. Details on the THESEUS mission concept can be found in the white paper Amati et al. 2017 (arXiv:171004638) and Stratta et al. 2017 (arXiv:1712.08153

Development and tests of a new prototype detector for the XAFS beamline at Elettra Synchrotron in Trieste

The XAFS beamline at Elettra Synchrotron in Trieste combines X-ray absorption spectroscopy and X-ray diffraction to provide chemically specific structural information of materials. It operates in the energy range 2.4-27 keV by using a silicon double reflection Bragg monochromator. The fluorescence measurement is performed in place of the absorption spectroscopy when the sample transparency is too low for transmission measurements or the element to study is too diluted in the sample. We report on the development and on the preliminary tests of a new prototype detector based on Silicon Drift Detectors technology and the SIRIO ultra low noise front-end ASIC. The new system will be able to reduce drastically the time needed to perform fluorescence measurements, while keeping a short dead time and maintaining an adequate energy resolution to perform spectroscopy. The custom-made silicon sensor and the electronics are designed specifically for the beamline requirements.Comment: Proceeding of the 6YRM 12th-14th Oct 2015 - L'Aquila (Italy). Accepted for publication on Journal of Physics: Conference Serie

LOFT - a Large Observatory For x-ray Timing

The high time resolution observations of the X-ray sky hold the key to a number of diagnostics of fundamental physics, some of which are unaccessible to other types of investigations, such as those based on imaging and spectroscopy. Revealing strong gravitational field effects, measuring the mass and spin of black holes and the equation of state of ultradense matter are among the goals of such observations. At present prospects for future, non-focused X-ray timing experiments following the exciting age of RXTE/PCA are uncertain. Technological limitations are unavoidably faced in the conception and development of experiments with effective area of several square meters, as needed in order to meet the scientific requirements. We are developing large-area monolithic Silicon Drift Detectors offering high time and energy resolution at room temperature, which require modest resources and operation complexity (e.g., read-out) per unit area. Based on the properties of the detector and read-out electronics that we measured in the lab, we developed a realistic concept for a very large effective area mission devoted to X-ray timing in the 2-30 keV energy range. We show that effective areas in the range of 10-15 square meters are within reach, by using a conventional spacecraft platform and launcher of the small-medium class.Comment: 13 pages, 8 figures, 1 table, Proceedings of SPIE Vol. 7732, Paper No. 7732-66, 201

Silicon strip detectors for two-dimensional soft X-ray imaging at normal incidence

A simple prototype system for static two-dimensional soft X-ray imaging using silicon microstrip detectors irradiated at normal incidence is presented. Radiation sensors consist of single-sided silicon detectors made from 300 mum thick wafers, read by RX64 ASICs. Data acquisition and control is performed by a Windows PC workstation running dedicated LabVIEW routines, connected to the sensors through a PCI-DIO-96 interface. Two-dimensional images are obtained by scanning a lead collimator with a thin slit perpendicular to the strip axis, along the whole detector size; the several strip profiles (slices) taken at each position are then put together to form a planar image. Preliminary results are presented, illustrating the high-resolution imaging capabilities of the system with soft X-rays. (C) 2003 Elsevier B.V. All rights reserved.info:eu-repo/semantics/publishedVersio

Steps towards the hyperfine splitting measurement of the muonic hydrogen ground state: pulsed muon beam and detection system characterization

The high precision measurement of the hyperfine splitting of the muonic-hydrogen atom ground state with pulsed and intense muon beam requires careful technological choices both in the construction of a gas target and of the detectors. In June 2014, the pressurized gas target of the FAMU experiment was exposed to the low energy pulsed muon beam at the RIKEN RAL muon facility. The objectives of the test were the characterization of the target, the hodoscope and the X-ray detectors. The apparatus consisted of a beam hodoscope and X-rays detectors made with high purity Germanium and Lanthanum Bromide crystals. In this paper the experimental setup is described and the results of the detector characterization are presented.Comment: 22 pages, 14 figures, published and open access on JINS