Strategies against nonsense: oxadiazoles as translational readthrough-inducing drugs (TRIDs)

This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison to aminoglycosides. Additionally, recent results on the efficiency of new candidate TRIDs in restoring the production of the cystic fibrosis transmembrane regulator (CFTR) protein will be presented. Finally, a prospectus on complementary strategies to enhance the effect of TRIDs will be illustrated together with a conclusive paragraph about perspectives, opportunities, and caveats in developing small molecules as TRIDs

EChO Payload electronics architecture and SW design

EChO is a three-modules (VNIR, SWIR, MWIR), highly integrated spectrometer, covering the wavelength range from 0.55 $\mu$m, to 11.0 $\mu$m. The baseline design includes the goal wavelength extension to 0.4 $\mu$m while an optional LWIR module extends the range to the goal wavelength of 16.0 $\mu$m. An Instrument Control Unit (ICU) is foreseen as the main electronic subsystem interfacing the spacecraft and collecting data from all the payload spectrometers modules. ICU is in charge of two main tasks: the overall payload control (Instrument Control Function) and the housekeepings and scientific data digital processing (Data Processing Function), including the lossless compression prior to store the science data to the Solid State Mass Memory of the Spacecraft. These two main tasks are accomplished thanks to the Payload On Board Software (P-OBSW) running on the ICU CPUs.Comment: Experimental Astronomy - EChO Special Issue 201

ONE-TROCAR VIDEO-ASSISTED STRIPPING TECHNIQUE FOR USE IN THE TREATMENT OF LARGE OVARIAN CYSTS IN INFANTS

Background Management of ovarian cysts in infants is controversial; it can be conservative or surgical, and the management is determined by the cyst''s size and sonographic features. Methods A surgical approach using a 10-mm umbilically placed operative laparoscope was taken in 3 female infants with antenatally diagnosed large, simple ovarian cysts. The contents of the cysts were partially aspirated and the cyst walls were stripped off the remaining ovarian parenchyma. No intraoperative or postoperative complications were recorded. Conclusions The one-trocar video-assisted stripping technique for large ovarian cysts in infants appears to be an ovarian-tissue-preserving procedure, and it sidesteps the disadvantages of large scars and formation of adhesions

Two Variables Algorithms for Solving the Stochastic Equilibrium Assignment with Variable Demand: Performance Analysis and Effects of Path Choice Models

In this paper a general fixed-point approach dealing with multi-user (stochastic) equilibrium assignment with variable demand is proposed. The main focus is on (i) the implementation and comparison of different algorithm solutions based on successive averages methods calculated on one (arc flows, arc costs) and on two variables (arc flows and path satisfaction; arc costs and demand flows); (ii) the effects of algorithm efficiency on different path choice models and/or travel demand choice models. In terms of the best performing algorithmic solution, the effects of different path choice models, such as Multinomial Logit model, C-Logit model and Multinomial Probit model were implemented, and algorithmic efficiency was investigated w.r.t. a real network

Breast Reconstruction and the Covid-19 Pandemic: Adapting Practice

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Can alexithymia be assessed through an interview in adolescents? The Toronto Structured Interview for Alexithymia: Reliability, concurrent validity, discriminant validity, and relationships with emotional-behavioral symptoms

Alexithymia is connected to adolescents' psychopathology, but the current methods of assessment present limitations. The Toronto Structured Interview for Alexithymia (TSIA) was developed to overcome the limits of the main used self-rating scale in adults, but no studies investigated its feasibility with adolescents. This study involved 95 community adolescents aged 12-19 years. Adolescents were assessed with the TSIA, the 20-item Toronto Alexithymia Scale (TAS-20), the Verbal Comprehension Index of the WISC-IV for verbal skills, and the Child Behavior Checklist and Youth Self Report for emotional-behavioral symptoms. The aims were to investigate the TSIA internal consistency, concurrent validity with the TAS-20, discriminant validity with participants' verbal skills, and relationships with emotional-behavioral symptoms. TSIA showed good internal consistency, concurrent validity with the TAS-20 (except for factor DDF), and independence by participants' verbal skills, but few relationships with emotional-behavioral symptoms. In conclusion, TSIA showed some good psychometric proprieties but little convergence with research findings obtained with the TAS-20, suggesting the need for further research to check the feasibility of using the TSIA with adolescents. Meanwhile, a precautionary multi-method assessment of alexithymia is recommended

Detection of the Vortex Dynamic Regimes in MgB2 by Third Harmonic AC Susceptibility Measurements

In a type-II superconductor the generation of higher harmonics in the magnetic response to an alternating magnetic field is a consequence of the non-linearity in the I-V relationship. The shape of the current-voltage (I-V) curve is determined by the current dependence of the thermal activation energy U(J) and is thus related to the dynamical regimes governing the vortex motion. In order to investigate the vortex dynamics in MgB2 bulk superconductors we have studied the fundamental (chi1) and third (chi3) harmonics of the ac magnetic susceptibility. Measurements have been performed as a function of the temperature and the dc magnetic field, up to 9 T, for various frequencies and amplitudes of the ac field. We show that the analysis of the behaviour in frequency of chi3(T) and chi3(B) curves can provide clear information about the non-linearity in different regions of the I-V characteristic. By comparing the experimental curves with numerical simulations of the non-linear diffusion equation for the magnetic field we are able to resolve the crossover between a dissipative regime governed by flux creep and one dominated by flux flow phenomena.Comment: to be published in "Horizons in Superconductivity Research" (Nova Science Publishers, Inc., NY, 2003

Ileocecal duplication cysts: Is the loss of the valve always necessary?

Ileocecal (IC) duplication cysts are enteric duplications located at the IC junction, not clearly identified in all the published series. The reported treatment is IC resection and ileocolic anastomosis. It is well known that the loss of the IC valve has several adverse effects. This study is aimed at demonstrating that cyst removal together with the common ileal wall and following enterorrhapy is possible, safe, and effective in preserving the IC region. Methods Medical records of 3 patients who underwent surgery for IC duplication between 2003 and 2013 were retrospectively reviewed evaluating follow-up results. Results All patients had an antenatal diagnosis of intrabdominal cystic mass. In two cases associated malformations were reported. The lesions presented at newborn age with intermittent small bowel obstruction and required removal. No patients underwent IC resection. The diagnosis of duplication cyst was confirmed by histo-pathologic examination. The postoperative course was uneventful, even in the long-term follow-up

Focus Point on Microplastic Pollution: Assessment, Effects and Mitigation Strategies

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The Visible and Near Infrared module of EChO

The Visible and Near Infrared (VNIR) is one of the modules of EChO, the Exoplanets Characterization Observatory proposed to ESA for an M-class mission. EChO is aimed to observe planets while transiting by their suns. Then the instrument had to be designed to assure a high efficiency over the whole spectral range. In fact, it has to be able to observe stars with an apparent magnitude Mv= 9-12 and to see contrasts of the order of 10-4 - 10-5 necessary to reveal the characteristics of the atmospheres of the exoplanets under investigation. VNIR is a spectrometer in a cross-dispersed configuration, covering the 0.4-2.5 micron spectral range with a resolving power of about 330 and a field of view of 2 arcsec. It is functionally split into two channels respectively working in the 0.4-1 and 1.0-2.5 micron spectral ranges. Such a solution is imposed by the fact the light at short wavelengths has to be shared with the EChO Fine Guiding System (FGS) devoted to the pointing of the stars under observation. The spectrometer makes use of a HgCdTe detector of 512 by 512 pixels, 18 micron pitch and working at a temperature of 45K as the entire VNIR optical bench. The instrument has been interfaced to the telescope optics by two optical fibers, one per channel, to assure an easier coupling and an easier colocation of the instrument inside the EChO optical bench.Comment: 26 page