43 research outputs found

    An efficient shortest path routing algorithm in the data centre network DPillar.

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    DPillar has recently been proposed as a server-centric data centre network and is combinatorially related to the well-known wrapped butterfly network. We explain the relationship between DPillar and the wrapped butterfly network before proving a symmetry property of DPillar. We use this symmetry property to establish a single-path routing algorithm for DPillar that computes a shortest path and has time complexity O(klog(n))O(klogā”(n)), where k parameterizes the dimension of DPillar and n the number of ports in its switches. Moreover, our algorithm is trivial to implement, being essentially a conditional clause of numeric tests, and improves significantly upon a routing algorithm earlier employed for DPillar. A secondary and important effect of our work is that it emphasises that data centre networks are amenable to a closer combinatorial scrutiny that can significantly improve their computational efficiency and performance

    Lessons learned from COVID-19 Lockdown: An ASPED/MENA Study on Lifestyle Changes and Quality of Life during Ramadan Fasting in Children and Adolescents living with Type 1 Diabetes

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    Background: Lockdown was a unique experience that affected many aspects of life, particularly during the challenge of Ramadan fasting (RF). Studying this can increase understanding of the effects of lifestyle changes on quality of life (QoL) for children with type 1 diabetes (T1D) during RF. Methods: A cross-sectional study that assessed the effect of lockdown on lifestyle and QoL on fasting children living with T1D during Ramadan in the Middle East and North Africa region (2020-2021). We compared the child (self) and parent (proxy) reports using PEDQoL v3.0 disease specific questionnaire during lockdown and non-lockdown periods, and assessed correlations with lifestyle changes using regression and gap analyses. Results: A total of 998 reports from 499 children with T1D aged 8-18 years (study=276, control=223), and their parents during RF in lockdown and non-lockdown periods. Fathers were more involved in their childrenā€™s care during lockdown (p=0.019). Patients had better compliance with treatment (p= 0.002), a reversed sleep pattern (p= 0.033), increased food intake (p=<0.001) and less exercise (p<0.001). Children and parents perceived better QoL during lockdown (p=<0.001) with no differences between their reports in ā€œDiabetes Symptomsā€, ā€œTreatment Adherenceā€ and ā€œCommunicationā€ domains. Self and proxy reports were different in all domains during non-lockdown (p-values <0.001- 0.009). In gap analysis, although not statistically significant, the gap was approximated between childrenā€™s and parentsā€™ perceptions in all domains during lockdown. Conclusion: COVID-19 lockdown had a positive impact on QoL of children living with T1D during RF, possibly due to lifestyle changes and superior psychosocial family dynamics

    Novel De Novo Mutation in Sulfonylurea Receptor 1 Presenting as Hyperinsulinism in Infancy Followed by Overt Diabetes in Early Adolescence

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    OBJECTIVEā€”Congenital hyperinsulinism, usually associated with severe neonatal hypoglycemia, may progress to diabetes, typically during the 4th decade of life in nonpancreatectomized patients. We aimed to genotype the ATP-sensitive K+ channel in a 10.5-year-old girl presenting with overt diabetes following hyperinsulinism in infancy

    SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission

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    SLC4A10 is a plasma-membrane bound transporter which utilizes the Na+ gradient to drive cellular HCO3- uptake, thus mediating acid extrusion. In the mammalian brain, SLC4A10 is expressed in principal neurons and interneurons, as well as in epithelial cells of the choroid plexus, the organ regulating the production of cerebrospinal fluid. Using next generation sequencing on samples from five unrelated families encompassing ten affected individuals, we show that biallelic SLC4A10 loss-of-function variants cause a clinically recognizable neurodevelopmental disorder in humans. The cardinal clinical features of the condition include hypotonia in infancy, delayed psychomotor development across all domains and typically severe intellectual impairment. Affected individuals commonly display traits associated with autistic spectrum disorders including anxiety, hyperactivity and stereotyped movements. In two cases isolated episodes of seizures were reported in the first few years of life, and a further affected child displayed bitemporal epileptogenic discharges on EEG without overt clinical seizures. While occipitofrontal circumference was reported to be normal at birth, progressive postnatal microcephaly evolved in 7 out of 10 affected individuals. Neuroradiological features included a relative preservation of brain volume compared to occipitofrontal circumference, characteristic narrow sometimes 'slit-like' lateral ventricles and corpus callosum abnormalities. Slc4a10 -/- mice, deficient for SLC4A10, also display small lateral brain ventricles and mild behavioral abnormalities including delayed habituation and alterations in the 2-object novel object recognition task. Collapsed brain ventricles in both Slc4a10-/- mice and affected individuals suggests an important role of SLC4A10 in the production of the cerebrospinal fluid. However, it is notable that despite diverse roles of the cerebrospinal fluid in the developing and adult brain, the cortex of Slc4a10-/- mice appears grossly intact. Co-staining with synaptic markers revealed that in neurons, SLC4A10 localizes to inhibitory, but not excitatory, presynapses. These findings are supported by our functional studies which show the release of the inhibitory neurotransmitter GABA is compromised in Slc4a10-/- mice, while the release of the excitatory neurotransmitter glutamate is preserved. Manipulation of intracellular pH partially rescues GABA release. Together our studies define a novel characteristic neurodevelopmental disorder associated with biallelic pathogenic variants in SLC4A10 and highlight the importance of further analyses of the consequences of SLC4A10 loss-of-function for brain development, synaptic transmission and network properties

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    Cloud Data Federation for Scientific Applications

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    Nowadays, data-intensive scientific research needs storage capabilities that enable efficient data sharing. This is of great importance for many scientific domains such as the Virtual Physiological Human. In this paper, we introduce a solution that federates a variety of systems ranging from file servers to more sophisticated ones used in clouds or grids. Our solution follows a client-centric approach that loosely couples a variety of data resources that may use different technologies such as Openstack-Swift, iRODS, GridFTP, and may be geographically distributed. It is implemented as a lightweight service which does not require installation of a software on the resources it uses. In this way we are able to efficiently use heterogeneous storage resources, reduce the usage complexity of multiple storage resources, and avoid vendor lock-in in case of cloud storage. To demonstrate the usability of our approach we performed a number of experiments that assess the performance and functionality of the developed system

    Organic Solute Transporter-beta (SLC51B) Deficiency in Two Brothers with Congenital Diarrhea and Features of Cholestasis

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    Primary bile acid malabsorption (PBAM) is associated with congenital diarrhea, steatorrhea, and a block in the intestinal return of bile acids in the enterohepatic circulation. Mutations in the ileal Na(+) -dependent bile acid transporter (ASBT; SLC10A2) can cause PBAM, but do not appear to account for most familial cases. Another major transporter involved in the intestinal reclamation of bile acids is the heteromeric Organic Solute Transporter alpha-beta (OSTĪ±-OSTĪ²; SLC51A-SLC51B), which exports bile acid across the basolateral membrane. Here we report the first patients with OSTĪ² deficiency, clinically characterized by chronic diarrhea, severe fat soluble vitamin deficiency, and features of cholestatic liver disease including elevated serum gamma-glutamyltransferase activity. Whole exome sequencing revealed a homozygous single nucleotide deletion in codon 27 of SLC51B, resulting in a frameshift and premature termination at codon 50. Functional studies in transfected cells showed that the SLC51B mutation resulted in markedly reduced taurocholic acid uptake activity and reduced expression of the OSTĪ± partner protein. The findings identify OSTĪ² deficiency as a new cause of congenital chronic diarrhea with features of cholestatic liver disease. These studies underscore OSTĪ±-OSTĪ²'s key role in the enterohepatic circulation of bile acids in humans. This article is protected by copyright. All rights reserve
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