Novel KCND3 Variant Underlying Nonprogressive Congenital Ataxia or SCA19/22 Disrupt KV4.3 Protein Expression and K+ Currents with Variable Effects on Channel Properties

KCND3 encodes the voltage-gated potassium channel K_V4.3 that is highly expressed in the cerebellum, where it regulates dendritic excitability and calcium influx. Loss-of-function K_V4.3 mutations have been associated with dominant spinocerebellar ataxia (SCA19/22). By targeted NGS sequencing, we identified two novel KCND3 missense variants of the K_V4.3 channel: p.S347W identified in a patient with adult-onset pure cerebellar syndrome and p.W359G detected in a child with congenital nonprogressive ataxia. Neuroimaging showed mild cerebellar atrophy in both patients. We performed a two-electrode voltage-clamp recording of K_V4.3 currents in Xenopus oocytes: both the p.G345V (previously reported in a SCA19/22 family) and p.S347W mutants exhibited reduced peak currents by 50%, while no K+ current was detectable for the p.W359G mutant. We assessed the effect of the mutations on channel gating by measuring steady-state voltage-dependent activation and inactivation properties: no significant alterations were detected in p.G345V and p.S347W disease-associated variants, compared to controls. K_V4.3 expression studies in HEK293T cells showed 53% (p.G345V), 45% (p.S347W) and 75% (p.W359G) reductions in mutant protein levels compared with the wildtype. The present study broadens the spectrum of the known phenotypes and identifies additional variants for KCND3-related disorders, outlining the importance of SCA gene screening in early-onset and congenital ataxia.     

Porous 3D printed concrete beams show an environmental promise: a cradle-to-grave comparative life cycle assessment

3D Concrete Printing (3DCP) is a rapidly expanding area in the field of architecture, engineering, and construction, but very limited research has quantitatively investigated its environmental impact. The existing Life Cycle Assessment (LCA) studies on 3DCP lack clearly defined functional units of comparison, especially considering load-bearing structures. This paper investigates the potential environmental benefits of 3DCP over conventional concrete construction for structural beams based on a cradle-to-grave comparative LCA. Unlike existing studies, this paper employs a recarbonation model to account for the carbon offsetting from the use-stage of 3DP concrete, which shows significant results. The assessment includes three-beam designs, each analyzed for both prefabrication and on-site construction scenarios. While currently, 3DCP has a generally higher environmental impact due to the larger quantity of cement employed in the process, the reduction of material through infill optimization for printed beams is a promising design principle to positively offset the environmental impacts in the construction sector. The paper draws recommendations for future research on material- and recarbonation-efficient 3DCP design for load-bearing structures, as well as on material development, e.g. integration of larger aggregates and low-clinker cement.

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TCMI: a non-parametric mutual-dependence estimator for multivariate continuous distributions

Data Mining and Knowledge Discovery - The identification of relevant features, i.e., the driving variables that determine a process or the properties of a system, is an essential part of the...     

A Computational Methodology for Assessing the Time‐Dependent Structural Performance of Electric Road Infrastructures

An infrastructure adapted to dynamic wireless recharging of electric vehicles is often referred to generically as Electric Road (“e‐road”). E‐roads are deemed to become essential components of future grid environments and smart city strategies. Several technologies already exist that propose different ways to integrate dynamic inductive charging systems within the infrastructure. One e‐road solution uses a very thin rail with box‐section made of fibre‐reinforced polymer, inside which an electric current flows producing a magnetic field. In spite of the great interest and research generated by recharging technologies, the structural problems of e‐roads, including vibrations and structural integrity in the short and/or long period, have received relatively little attention to date. This article presents a novel computational methodology for assessing the time‐dependent structural performance of e‐roads, including a recursive strategy for the estimation of the lifetime of surface layers. The article also reports some numerical findings about e‐roads that will drive further numerical analyses and experimental studies on this novel type of infrastructure. Finally, numerical simulations have been conducted to compare an e‐road with a traditional road (“t‐road”), in terms of static, dynamic and fatigue behavior.     

Diagrid structures for tall buildings: case studies and design considerations

The originality of form is one of the new trends that can be identified in the current design of tall buildings. In this design trend, the so‐called diagrid structures, which represent the latest mutation of tubular structures, play a major role due to their inherent esthetic quality, structural efficiency and geometrical versatility. In this paper, an overview on application of such typology to high‐rise buildings is carried out; in particular, in the first part of the paper, the peculiarities of diagrid systems are described: starting from the analysis of the internal forces arising in the single diagrid module due to vertical and horizontal loads, the resisting mechanism of diagrid buildings under gravity and wind loads is described, and recent researches and studies dealing with the effect of geometry on the structural behavior are discussed. In the second part of the paper, a comparative analysis of the structural performance of some recent diagrid tall buildings, characterized by different number of stories and different geometries, namely the Swiss Re building in London, the Hearst Headquarters in New York and the West Tower in Guangzhou, is carried out, and some general design remarks are derived. Copyright © 2012 John Wiley & Sons, Ltd.     

Simulation modelling for groundwater safety in an overexploitation situation: the Maggiore Valley context (Piedmont,Italy)

The Maggiore Valley well field plays a fundamental role in supplying drinking water to a large territory of the Piedmont (north-western Italy). However, an increasing demand for water has led to the overexploitation of the groundwater resources. This situation has caused a progressive drawdown of the piezometric level (locally, up to 0.8 m/year), a spatial reduction in the artesian zone, localised land subsidence and damage to wells. The main purpose of this study was the development of a groundwater flow model of the area for analysing the aquifer response to various pumping strategies. Initially, the groundwater flow simulation (achieved by the application of the MODFLOW code) was calibrated satisfactorily. Then, the groundwater response to four scenarios was simulated to explore the best option to mitigate the problem. In three of the scenarios, a withdrawal reduction of 110 l/s was simulated, whilst considering various relocation options for extraction within the well field. The fourth scenario simulated a withdrawal reduction of 150 l/s; this option also assumed a supplementary water supply from the Monferrato Aqueduct, located north of the study area. All the simulations provided an increase in the piezometric level; in some instances, up to 30 m. Based on these simulations, the most promising management strategy for the Maggiore Valley well field would seem to be the option using a supplementary feed from the Monferrato Aqueduct. In this instance, the predicted piezometric level rise would be up to 25 m; this option also precludes the need for drilling additional wells.