Clinical features of the pathogenic m.5540G>A mitochondrial transfer RNA tryptophan gene mutation

AbstractMitochondrial DNA disease is one of the most common groups of inherited neuromuscular disorders and frequently associated with marked phenotypic and genotypic heterogeneity. We describe an adult patient who initially presented with childhood-onset ataxia without a family history and an unremarkable diagnostic muscle biopsy. Subsequent multi-system manifestations included basal ganglia calcification, proteinuria, cataract and retinitis pigmentosa, prompting a repeat muscle biopsy that showed features consistent with mitochondrial myopathy 13 years later. She had a stroke with restricted diffusion change in the basal ganglia and internal capsule at age 44 years. Molecular genetic testing identified a previously-reported pathogenic, heteroplasmic mutation in the mitochondrial-encoded transfer RNA tryptophan (MT-TW) gene which based on family studies was likely to have arisen de novo in our patient. Interestingly, we documented an increase in the mutant mtDNA heteroplasmy level in her second biopsy (72% compared to 56%), reflecting the progression of clinical disease

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

The Design and Implementation of a Novel Open Source Massive Deployment System

The hypervisor and container are emerging cloud computing and fog computing technologies, which enable rapid system deployment. However, both of the technologies depend on the operating system (OS) and applications that are installed on the host machines. System deployment is the activity to deliver and install OSs and applications onto computers. Such deployment activities are widely required in the infrastructure of cloud computing, fog computing, high-performance computing clusters, and classrooms of computer education. Albeit the concept of system deployment is not new, traditional solutions cannot support the rapid evolution of open source file systems. Furthermore, existing solutions cannot support the massive deployment of disks in a computer as well as the massive deployment in large-scale computers. To resolve the issue, the authors proposed novel system architecture as well as software that is openly available. The experiments are undertaken by deploying a Linux system to 1 to 30 Universal Serial Bus (USB) flash drives in a single machine and to 1 to 32 machines in a network using the software that is being developed in this work. The results have demonstrated the feasibility and efficiency of the proposed work. The relationships between the bus bandwidth, the writing rate of the USB flash drive, and the number of flash drives were also formulated as a govern equation. Performance evaluation and cost savings in comparing to the deployment cases adopting commercial software were also provided for demonstrating the performance enhancement and cost reduction by using the novel deployment system. In general, the proposed architecture and the developed software are highly effective from the aspects of both performance and cost

A Derivation of Factors Influencing the Diffusion and Adoption of an Open Source Learning Platform

During the past two decades, open source learning platforms (OSLPs) have become a dominant part of modern education. OSLPs are free for usage and customization—unlike proprietary software restricted by copyright licenses. By utilizing OSLPs, users can download and use the source code, write new features, fix bugs, improve performances, or learn from others how specific problems can be solved. Albeit dominant, the frequency of usage and motivation of OSLPs by students is not high; however, there has been very little research about this, and the problem is significant. Therefore, this research aimed to derive the factors that affect the adoption and diffusion of OSLPs. The factors on the diffusion and adoption were defined based on the innovation diffusion theory (IDT) and the technology acceptance model (TAM), where the integrated theoretical framework is called the IDT-TAM. Partial Least Square structural equation modeling was used to confirm the hypothesized IDT-TAM. An empirical study was based on the sample data collected from 340 Taiwanese technical university students to demonstrate the feasibility of the analytical framework and derive the factors related to the adoption and diffusion of the OSLP for students. Based on the results of the empirical study, through the mediation of perceived attitude (PA) and perceived usefulness (PU), trialability (TL), observability (OS), ease of use (EU), and relative advantage (RA) are the factors most related to the diffusion and acceptance of the OSLP innovations. The analytical results can serve as the basis for the design, development, and enhancement of acceptance and diffusion of OSLP

A Derivation of Factors Influencing the Innovation Diffusion of the OpenStreetMap in STEM Education

Geographic information is a confluence of knowledge from spatial science, information technologies, engineering, and mathematics, etc. Effective spatial training can enhance achievement in science, technology, engineering, and mathematics (STEM) education. Therefore, the geographic information system (GIS) plays a daily role in modern STEM education. Volunteered Geographical Information (VGI) is characterized by the openness of the geographic information being generated and accumulated by volunteers. Within the VGI sphere, OpenStreetMap (OSM) is one of the most well-known VGI due to its openness, flexibility, cost-effectiveness, and web-based mapping capability, making it one of the best alternatives for use as the mapping application for STEM education. However, very few or no prior works have investigated the factors influencing the innovation diffusion of OSM in STEM education. Therefore, to fill this gap, this work aims to investigate these factors. To achieve this purpose, the authors have defined an analytic framework based on innovation diffusion theory (IDT) and the technology acceptance model (TAM). The factors influencing students’ acceptance and intention to continue using and diffusing OSM in STEM education will be investigated. Partial least squares structural equation modeling (PLS-SEM) was used to confirm the hypothesized IDT–TAM integrated model. An empirical study based on sample data collected from 145 Taiwanese undergraduate and graduate students from engineering-related institutes was used to demonstrate the feasibility of the proposed analytic framework and to derive the factors related to the adoption and diffusion of OSM in STEM education. The proposed theoretical framework forged in this study was proven to be successful. Based on the empirical study results, ease of use, observability, and compatibility are the most influential factors in OSM diffusion. Therefore, activities that enhance the ease of use, observability, and compatibility of OSM should be emphasized so that STEM students’ perception of the usefulness of the technology and their perceived attitude towards it leads to the intention to continue the use of OSM. The analytic results can serve as a foundation for the design, development, and accelerated adoption and diffusion of OSM in STEM education

The Design and Implementation of a Novel Open Source Massive Deployment System

The hypervisor and container are emerging cloud computing and fog computing technologies, which enable rapid system deployment. However, both of the technologies depend on the operating system (OS) and applications that are installed on the host machines. System deployment is the activity to deliver and install OSs and applications onto computers. Such deployment activities are widely required in the infrastructure of cloud computing, fog computing, high-performance computing clusters, and classrooms of computer education. Albeit the concept of system deployment is not new, traditional solutions cannot support the rapid evolution of open source file systems. Furthermore, existing solutions cannot support the massive deployment of disks in a computer as well as the massive deployment in large-scale computers. To resolve the issue, the authors proposed novel system architecture as well as software that is openly available. The experiments are undertaken by deploying a Linux system to 1 to 30 Universal Serial Bus (USB) flash drives in a single machine and to 1 to 32 machines in a network using the software that is being developed in this work. The results have demonstrated the feasibility and efficiency of the proposed work. The relationships between the bus bandwidth, the writing rate of the USB flash drive, and the number of flash drives were also formulated as a govern equation. Performance evaluation and cost savings in comparing to the deployment cases adopting commercial software were also provided for demonstrating the performance enhancement and cost reduction by using the novel deployment system. In general, the proposed architecture and the developed software are highly effective from the aspects of both performance and cost

A Novel Massive Deployment Solution Based on the Peer-to-Peer Protocol

: The BitTorrent (BT) is a peer-to-peer (P2P) file sharing protocol that was developed approximately 20 years ago, is becoming increasingly popular, and has been widely accepted. The BT-based mass deployment system can be used to improve performance and scalability that cannot be achieved by the unicasting, broadcasting, and multicasting protocols. However, when the BT-based system is applied in massive deployments, a major issue related to insufficient temporary storage space to store the whole system image before deploying needs to be resolved. Such problems arose because the system is deployed to the disk space, meaning that it cannot be used for temporary storage. Therefore, a novel BT-based solution that can remove the limitations caused by the insufficient temporary storage issue is proposed. The BT-based mass deployment system was designed by using the file system blocks transferring (FSBT) mechanism. The receiver of the FSBT mechanism can obtain the blocks of the file system from other peers. Then, those blocks will be written directly to raw disks or partitions. The sender of the FSBT mechanism can read the blocks of file systems directly from raw disks or partitions. Then, the blocks can be sent to other peers. This approach solves the insufficient temporary storage issue. The novel BT-based mass deployment system was tested and verified for the configuration consisting of at most 32 personal computers (PCs). To demonstrate the achievable performance of the novel BT-based system, comparisons were made between the novel program and the traditional multicast solutions, as well as other solutions for mass deployment. The proposed BT solution can be much faster than the multicast solution when deploying 11 machines or more. The experimental results demonstrated the feasibility and superior performance of the proposed system. Furthermore, performance comparisons of the proposed BT-based mass deployment system versus other solutions demonstrated the feasibility and efficiency of the proposed solution. In the future, the BT parameters can be further optimized, and the simultaneous read and write features can be implemented to improve the deployment performance. In addition, the BT-based mass deployment system can serve as the basis for the development of other mass deployment systems

Adeno-associated virus type 2 in US children with acute severe hepatitis

As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein-Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses