Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele

Experiences of wearing support garments by people living with a urostomy

BACKGROUND:support garments are commonly worn by people with a urostomy but there are no published data about their experiences of doing so. AIMS:to identify the views of people living with a urostomy on the role of support garments. METHODS:a cross-sectional survey of the stoma population's experiences of support garments was conducted in 2018. Recruitment was by social media. The free-text responses provided by a sub-sample of 58 people out of 103 respondents with a urostomy, were analysed. FINDINGS:thematic analysis revealed four themes: physical self-management; psychosocial self-management; lifestyle; and healthcare advice and support. There were mixed feelings about the value of support garments. Many cited a sense of reassurance and confidence and being able to be more sociable and active; others reported discomfort and uncertainty about their value. CONCLUSION:these findings add new understanding of experiences of support garments and provide novel theoretical insights about life with a urostomy

İki küçük avcının korkunç sergüzeştleri

M. K.'nın Yeni Yol'da tefrika edilen İki Küçük Avcının Korkunç Sergüzeştleri adlı romanıArşivdeki eksikler nedeniyle romanın tam metni verilememiştir. Bkz. Tefrika bilgi form

Goal-Directed Reasoning and Cooperation in Robots in Shared Workspaces: an Internal Simulation Based Neural Framework

From social dining in households to product assembly in manufacturing lines, goal-directed reasoning and cooperation with other agents in shared workspaces is a ubiquitous aspect of our day-to-day activities. Critical for such behaviours is the ability to spontaneously anticipate what is doable by oneself as well as the interacting partner based on the evolving environmental context and thereby exploit such information to engage in goal-oriented action sequences. In the setting of an industrial task where two robots are jointly assembling objects in a shared workspace, we describe a bioinspired neural architecture for goal-directed action planning based on coupled interactions between multiple internal models, primarily of the robot’s body and its peripersonal space. The internal models (of each robot’s body and peripersonal space) are learnt jointly through a process of sensorimotor exploration and then employed in a range of anticipations related to the feasibility and consequence of potential actions of two industrial robots in the context of a joint goal. The ensuing behaviours are demonstrated in a real-world industrial scenario where two robots are assembling industrial fuse-boxes from multiple constituent objects (fuses, fuse-stands) scattered randomly in their workspace. In a spatially unstructured and temporally evolving assembly scenario, the robots employ reward-based dynamics to plan and anticipate which objects to act on at what time instances so as to successfully complete as many assemblies as possible. The existing spatial setting fundamentally necessitates planning collision-free trajectories and avoiding potential collisions between the robots. Furthermore, an interesting scenario where the assembly goal is not realizable by either of the robots individually but only realizable if they meaningfully cooperate is used to demonstrate the interplay between perception, simulation of multiple internal models and the resulting complementary goal-directed actions of both robots. Finally, the proposed neural framework is benchmarked against a typically engineered solution to evaluate its performance in the assembly task. The framework provides a computational outlook to the emerging results from neurosciences related to the learning and use of body schema and peripersonal space for embodied simulation of action and prediction. While experiments reported here engage the architecture in a complex planning task specifically, the internal model based framework is domain-agnostic facilitating portability to several other tasks and platforms

Crise de abastecimento de água em São Paulo e falta de planejamento estratégico

Embora a crise no abastecimento de água na Região Metropolitana de São Paulo (RMSP) tenha se manifestado de maneira mais intensa no verão de 2013-2014, ela revela um problema crônico que vem afetando toda a Região nos últimos dez anos. Esse problema foi gerado pela falta de um planejamento estratégico que considere questões climatológicas que podem indicar, com meses de antecedência, problemas de recomposição dos níveis dos mananciais, permitindo que ações sejam empreendidas com razoável antecedência, reduzindo os impactos para a população. Este estudo mostra como é possível utilizar informações climáticas na gestão estratégica do sistema de abastecimento da RMSP.Though the crisis in the water supplying system in the Metropolitan Region of São Paulo (RMSP) was more intensively felt in the 2013-2014 summer, it reveals a chronic problem that has been affecting the whole RMSP for the past ten years. This problem is originated from the lack of a strategic planning that takes into consideration climate issues that could, months before, foresee problems to restore the levels of water resources, allowing measures to be implemented within a reasonable anticipation, therefore reducing the impacts on the population. This study shows how it is possible to use climate information in the strategic management of the water supply in the RMSP

Combining and solving sequence dependent traveling salesman and quadratic assignment problems in PCB assembly

Due to copyright restrictions, the access to the full text of this article is only available via subscription.In this study we undertake the optimization of chip shooter component placement machines which became popular in assembling printed circuit boards (PCB) in recent years. A PCB is usually a rectangular plastic board on which the electrical circuit to be used in a particular electronic equipment is printed. The overall optimization of the chip shooter placement machines leads to a very complicated optimization problem which we formulate here for the first time (without any simplifying assumptions). However, it is possible to decompose the problem into placement sequencing problem and feeder configuration problem which turn out to be sequence dependent traveling salesman problem (SDTSP) and Quadratic Assignment Problem (QAP), respectively. We use simulated annealing metaheuristic approach and the heuristics developed for the SDTSP in an earlier study to solve these two problems in an iterative manner. We also attempt to solve the combined overall optimization problem by simulated annealing and artificial bee colony metaheuristics and compare their performances with the iterative approach. The results are in favor of iterative approach.TÜBİTAK ; Marmara University Scientific Research Committe

Application of sequence-dependent traveling salesman problem in printed circuit board assembly

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Optimization issues regarding the automated assembly of printed circuit boards attracted the interest of researchers for several decades. This is because even small gains in assembly time result in very important benefits in mass production. In this paper, the focus is on a particular placement machine type that has a rotational turret and a stationary component magazine. So far, this type of machine received little attention among the researchers. In this paper, the feeder configuration, placement sequencing, and assembly time minimization problems are formulated explicitly and completely (without simplifying assumptions) using nonlinear integer programming. In addition, the placement sequencing problem is shown to be a recently introduced new generalization of the traveling salesman problem (the sequence-dependent traveling salesman). These formulations show the complexity of the problems and the need for effective heuristic designs for solving them. We propose three heuristics that improve previously suggested solution methods and give comparable results when compared to simulated annealing that is a widely accepted good performing metaheuristic on combinatorial optimization problems. The heuristics are experimentally shown to improve previous methods significantly in assembly time that implies a huge economic benefit. The heuristics proposed could also be applied to other placement machines with similar operation principles.TÜBİTA

Supporting NPD teams in innovation: Structuring user data on the foundations of empathy

Gathering and analyzing user data in new product development (NPD), both qualitative and quantitative, can be a strong driver for innovation in companies. While ideally user data should be obtained through direct interactions between NPD departments and targeted users, time and cost restrictions often make this impossible within organisations. Moreover, in larger companies, user data is not always shared across departments and/or is not presented in a way that is useful for NPD departments. This paper presents a tool specially developed for the NPD department of a large company in the retail branche to collect and combine user data generated by various departments and use this for inspiration for new product ideas. The tool is based on theory of empathy in design and on the requirements of the NPD department of this companyProduct Innovation ManagementIndustrial Design Engineerin

Cooling Strategy Optimization of a Permanent Magnet Synchronous Motor

In this study, 250 kW, 9 phase, outer rotor types of Permanent Magnet Synchronous Motor (PMSM) are taken into consideration. To optimize the cooling efficiency of the motor, firstly, the motor geometry is obtained, and the e-magnetic model of the geometry is validated with the manufacturer`s data. Secondly, by using the validated e-magnetic model, the cooling system of the motor was analyzed by using the thermal model of the Motor-CAD. The thermal model is also validated with the real-time experiments which are held on an electric bus at constant speed experimentally. For finding the best cooling strategy for the motor, after validation, the effect of the mass flow rate, the type of the cooling refrigerant, the cooling pipe diameter size, and the change of torque are analyzed on the validated model. The results showed us that mass flow rate and torque have a significant effect on winding temperature, and the Taguchi method showed that [mass flow rate (A)=50 l/min, pipe diameter (B) = 17.7 mm, number of turns (C)=20, type of fluid (D)= EGW50/50, torque (E)=2000 Nm] is the best cooling design parameters for the cooling strategy of the considered PMSM