Dynamical signature of a domain phase transition in a perpendicularly-magnetized ultrathin film

Domain phases in ultrathin Fe/Ni/W(110) films with perpendicular anisotropy have been studied using the ac magnetic susceptibility. Dynamics on time scales of minutes to hours were probed by quenching the system from high temperature to the stripe phase region, and varying the constant rate of temperature increase as the susceptibility traces were measured. The entire susceptibility peak is observed to relax slowly along the temperature axis, with the peak temperature increasing as the rate of heating is decreased. This is precisely opposite to what would happen if this slow relaxation was driven by changes in the domain density within the stripe phase. The data are instead consistent with a simple model for the removal of a significant density of pattern defects and curvature trapped in the quench from high temperature. A quantitative analysis confirms that the relaxation dynamics are consistent with the mesoscopic rearrangement of domains required to remove pattern defects, and that the experiment constitutes a "dynamical" observation of the phase transition from a high temperature, positionally disordered phase to the low temperature, ordered stripe phase.Comment: 8 two column pages, 5 figures, full article with extra data figure

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

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 children’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 “Diabetes Symptoms”, “Treatment Adherence” and “Communication” 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 children’s and parents’ 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

SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission

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

Towards User Centric Data Governance and Control in the Cloud

Part 5: Problems in the CloudInternational audienceCloud Computing, i. e. providing on-demand access to virtualised computing resources over the Internet, is one of the current mega-trends in IT. Today, there are already several providers offering cloud computing infrastructure (IaaS), platform (PaaS) and software (SaaS) services. Although the cloud computing paradigm promises both economical as well as technological advantages, many potential users still have reservations about using cloud services as this would mean to trust a cloud provider to correctly handle their data according to previously negotiated rules. Furthermore, the virtualisation causes a location independence of offered services which could interfere with domain specific legislative regulations. In this paper, we present an approach of putting the cloud user back into power when migrating data and services into and within the cloud. We outline our work in progress, that aims at providing a platform for developing flexible service architectures for cloud computing with special consideration of security and non-functional properties

Infantile neurodegenerative disorder associated with mutations in TBCD, an essential gene in the tubulin heterodimer assembly pathway

© The Author 2016. Published by Oxford University Press. Mutation in a growing spectrum of genes is known to either cause or contribute to primary or secondary microcephaly. In primary microcephaly the genetic determinants frequently involve mutations that contribute to or modulate the microtubule cytoskeleton by causing perturbations of neuronal proliferation and migration. Here we describe four patients from two unrelated families each with an infantile neurodegenerative disorder characterized by loss of developmental milestones at 9-24 months of age followed by seizures, dystonia and acquired microcephaly. The patients harboured homozygous missense mutations (A475T and A586V) in TBCD, a gene encoding one of five tubulin-specific chaperones (termed TBCA-E) that function in concert as a nanomachine required for the de novo assembly of the a/b tubulin heterodimer. The latter is the subunit from which microtubule polymers are assembled. We found a reduced intracellular abundance of TBCD in patient fibroblasts to about 10% (in the case of A475T) or 40% (in the case of A586V) compared to age-matched wild type controls. Functional analyses of the mutant proteins revealed a partially compromised ability to participate in the heterodimer assembly pathway. We show via in utero shRNA-mediated suppression that a balanced supply of tbcd is critical for cortical cell proliferation and radial migration in the developing mouse brain. We conclude that TBCD is a novel functional contributor to the mammalian cerebral cortex development, and that the pathological mechanism resulting from the mutations we describe is likely to involve compromised interactions with one or more TBCD-interacting effectors that influence the dynamics and behaviour of the neuronal cytoskeleton

RECON syndrome is a genome instability disorder caused by mutations in the DNA helicase RECQL1

Despite being the first homolog of the bacterial RecQ helicase to be identified in humans, the function of RECQL1 remains poorly characterized. Furthermore, unlike other members of the human RECQ family of helicases, mutations in RECQL1 have not been associated with a genetic disease. Here, we identify 2 families with a genome instability disorder that we have named RECON (RECql ONe) syndrome, caused by biallelic mutations in the RECQL gene. The affected individuals had short stature, progeroid facial features, a hypoplastic nose, xeroderma, and skin photosensitivity and were homozygous for the same missense mutation in RECQL1 (p.Ala459Ser), located within its zinc binding domain. Biochemical analysis of the mutant RECQL1 protein revealed that the p.A459S missense mutation compromised its ATPase, helicase, and fork restoration activity, while its capacity to promote single-strand DNA annealing was largely unaffected. At the cellular level, this mutation in RECQL1 gave rise to a defect in the ability to repair DNA damage induced by exposure to topoisomerase poisons and a failure of DNA replication to progress efficiently in the presence of abortive topoisomerase lesions. Taken together, RECQL1 is the fourth member of the RecQ family of helicases to be associated with a human genome instability disorder

Global Emergencies in Child Health: Challenges and Solutions—Viewpoint and Recommendations from the European Paediatric Association and the International Pediatric Association

Global emergencies, including natural disasters, epidemics, drought, armed conflicts, and the SARS-CoV-2 pandemic, have affected populations on five continents, causing devastating socioeconomic effects.Children are a most vulnerable and defenseless group. In tense situations, they feel overwhelmed and insecure and are often left to their own devices. Their rights to protection and integrity are threatened.3 The European Paediatric Association, Union of the National European Paediatrics Societies and Associations and the International Pediatric Association, representing the national pediatric societies from 149 countries, held a joint conference on October 9, 2021, in Zagreb, Croatia, to discuss the issue of global emergencies in pediatrics and their significant economic and social impact. Delegates discussed the challenges posed by a wide variety of emergencies in the context of increasing global complexities, while also exploring possible solutions. This article, prepared by the European Paediatric Association, Union of the National European Paediatrics societies and Associations–International Pediatric Association working group, includes the viewpoint and recommendations from the conference he group strongly recommends that countries develop, reorganize, and strengthen their health systems to address the social and environmental issues caused by global emergencies to enable more efficient and effective allocation and use of available resources for disaster preparedness and emergency response resources in communities. The statement emphasizes the importance of active involvement of all stakeholders, including governments and healthcare professionals. Their joint effort should focus on developing strategic partnerships with key international constituencies, such as the diplomatic, nongovernmental, legal, and academic communities, and the media with the aim of providing adequate support to infants, children, and adolescents affected by adversities.6 Pediatricians and their professional societies across the world must collaborate and share their experiences with new and emerging challenges in child health and together mitigate against inequalities within and between countries and between continents and together strongly and courageously advocate for the health and well-being of children