Characterization of a rare variant (c.2635-2A>G) of the MSH2 gene in a family with Lynch syndrome

Abstract Introduction: Lynch syndrome is caused by germline mutations in one of the mismatch repair genes (MLH1, MSH2, MSH6, and PMS2) or in the EPCAM gene. Lynch syndrome is defined on the basis of clinical, pathological, and genetic findings. Accordingly, the identification of predisposing genes allows for accurate risk assessment and tailored screening protocols. Case Description: Here, we report a family case with three family members manifesting the Lynch syndrome phenotype, all of which harbor the rare variant c.2635-2A>G affecting the splice site consensus sequence of intron 15 of the MSH2 gene. This mutation was previously described only in one family with Lynch syndrome, in which mismatch repair protein expression in tumor tissues was not assessed. In this study, we report for the first time the molecular characterization of the MSH2 c.2635-2A>G variant through in silico prediction analysis, microsatellite instability, and mismatch repair protein expression experiments on tumor tissues of Lynch syndrome patients. The potential effect of the splice site variant was revealed by three splicing prediction bioinformatics tools, which suggested the generation of a new cryptic splicing site. The potential pathogenic role of this variant was also revealed by the presence of microsatellite instability and the absence of MSH2/MSH6 heterodimer protein expression in the tumor cells of cancer tissues of the affected family members. Conclusions: We provide compelling evidence in favor of the pathogenic role of the MSH2 variant c.2635-2A>G, which could induce an alteration of the canonical splice site and consequently an aberrant form of the protein product (MSH2)

Assessing the inter-method reliability and correlational validity of the Body Type Dictionary (BTD)

The political negotiation, erection, and fall of national and cultural borders represent an issue that frequently occupies the media. Given the historical importance of boundaries as a marker of cultural identity, as well as their function to separate and unite people, the Body Type Dictionary (BTD; Wilson, 2006) represents a suitable computerized content analysis measure to analyse vocabulary qualified to measure body boundaries and their penetrability. Out of this context, this study aimed to assess the inter-method reliability of the BTD (Wilson, 2006) in relation to Fisher and Cleveland’s (1956, 1958) manual scoring system for high and low barrier personalities. The results indicated that Fisher and Cleveland’s manually coded barrier and penetration imagery scores showed an acceptable positive correlation with the computerized frequency counts of the BTD’s coded barrier and penetration imagery scores, thereby indicating an inter-method reliability. In addition, barrier and penetration imagery correlated positively with primordial thought language in the picture response test, and narratives of everyday and dream memories, thereby indicating correlational validity

Trapping in irradiated p-on-n silicon sensors at fluences anticipated at the HL-LHC outer tracker

The degradation of signal in silicon sensors is studied under conditions expected at the CERN High-Luminosity LHC. 200 $\mu$m thick n-type silicon sensors are irradiated with protons of different energies to fluences of up to $3 \cdot 10^{15}$ neq/cm$^2$. Pulsed red laser light with a wavelength of 672 nm is used to generate electron-hole pairs in the sensors. The induced signals are used to determine the charge collection efficiencies separately for electrons and holes drifting through the sensor. The effective trapping rates are extracted by comparing the results to simulation. The electric field is simulated using Synopsys device simulation assuming two effective defects. The generation and drift of charge carriers are simulated in an independent simulation based on PixelAV. The effective trapping rates are determined from the measured charge collection efficiencies and the simulated and measured time-resolved current pulses are compared. The effective trapping rates determined for both electrons and holes are about 50% smaller than those obtained using standard extrapolations of studies at low fluences and suggests an improved tracker performance over initial expectations

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

Test beam performance measurements for the Phase I upgrade of the CMS pixel detector

A new pixel detector for the CMS experiment was built in order to cope with the instantaneous luminosities anticipated for the Phase I Upgrade of the LHC. The new CMS pixel detector provides four-hit tracking with a reduced material budget as well as new cooling and powering schemes. A new front-end readout chip mitigates buffering and bandwidth limitations, and allows operation at low comparator thresholds. In this paper, comprehensive test beam studies are presented, which have been conducted to verify the design and to quantify the performance of the new detector assemblies in terms of tracking efficiency and spatial resolution. Under optimal conditions, the tracking efficiency is (99.95 ± 0.05) %, while the intrinsic spatial resolutions are (4.80 ± 0.25) μm and (7.99 ± 0.21) μm along the 100 μm and 150 μm pixel pitch, respectively. The findings are compared to a detailed Monte Carlo simulation of the pixel detector and good agreement is found.Peer reviewe

Performance studies of the CMS strip tracker before installation

Peer reviewe

Characterisation of irradiated thin silicon sensors for the CMS phase II pixel upgrade

The high luminosity upgrade of the Large Hadron Collider, foreseen for 2026, necessitates the replacement of the CMS experiment's silicon tracker. The innermost layer of the new pixel detector will be exposed to severe radiation, corresponding to a 1 MeV neutron equivalent fluence of up to Phi(eq) = 2x10(16) cm(-2), and an ionising dose of approximate to 5 MGy after an integrated luminosity of 3000 fb(-1). Thin, planar silicon sensors are good candidates for this application, since the degradation of the signal produced by traversing particles is less severe than for thicker devices. In this paper, the results obtained from the characterisation of 100 and 200 mu m thick p-bulk pad diodes and strip sensors irradiated up to fluences of Phi(eq) = 1.3 x 10(16) cm(-2) are shown.Peer reviewe

Selection of the silicon sensor thickness for the Phase-2 upgrade of the CMS Outer Tracker

During the operation of the CMS experiment at the High-Luminosity LHC the silicon sensors of the Phase-2 Outer Tracker will be exposed to radiation levels that could potentially deteriorate their performance. Previous studies had determined that planar float zone silicon with n-doped strips on a p-doped substrate was preferred over p-doped strips on an n-doped substrate. The last step in evaluating the optimal design for the mass production of about 200 m$^{2}$ of silicon sensors was to compare sensors of baseline thickness (about 300 μm) to thinned sensors (about 240 μm), which promised several benefits at high radiation levels because of the higher electric fields at the same bias voltage. This study provides a direct comparison of these two thicknesses in terms of sensor characteristics as well as charge collection and hit efficiency for fluences up to 1.5 × 10$^{15}$ n$_{eq}$/cm$^{2}$. The measurement results demonstrate that sensors with about 300 μm thickness will ensure excellent tracking performance even at the highest considered fluence levels expected for the Phase-2 Outer Tracker