592 research outputs found
Recombination lifetimes in gamma-irradiated P-type float zone silicon
Electron decay rate and absorption cross sections for electron holes and recombination in gamma irradiated n-type silico
Recombination lifetimes in gamma-irradiated silicon
Recombination lifetimes of minority carriers measured as function of temperature in silicon before and after irradiation by cobalt 60 gamma ray
APOE ε4 and exercise interact in a sex-specific manner to modulate dementia risk factors
Abstract
Introduction: Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer\u27s disease and related dementias (ADRDs), affecting many different pathways that lead to cognitive decline. Exercise is one of the most widely proposed prevention and intervention strategies to mitigate risk and symptomology of ADRDs. Importantly, exercise and APOE ε4 affect similar processes in the body and brain. While both APOE ε4 and exercise have been studied extensively, their interactive effects are not well understood.
Methods: To address this, male and female APOE ε3/ε3, APOE ε3/ε4, and APOE ε4/ε4 mice ran voluntarily from wean (1 month) to midlife (12 months). Longitudinal and cross-sectional phenotyping were performed on the periphery and the brain, assessing markers of risk for dementia such as weight, body composition, circulating cholesterol composition, murine daily activities, energy expenditure, and cortical and hippocampal transcriptional profiling.
Results: Data revealed chronic running decreased age-dependent weight gain, lean and fat mass, and serum low-density lipoprotein concentration dependent on APOE genotype. Additionally, murine daily activities and energy expenditure were significantly influenced by an interaction between APOE genotype and running in both sexes. Transcriptional profiling of the cortex and hippocampus predicted that APOE genotype and running interact to affect numerous biological processes including vascular integrity, synaptic/neuronal health, cell motility, and mitochondrial metabolism, in a sex-specific manner.
Discussion: These data in humanized mouse models provide compelling evidence that APOE genotype should be considered for population-based strategies that incorporate exercise to prevent ADRDs and other APOE-relevant diseases
The APOEε3/ε4 Genotype Drives Distinct Gene Signatures in the Cortex of Young Mice
Introduction: Restrictions on existing APOE mouse models have impacted research toward understanding the strongest genetic risk factor contributing to Alzheimer\u27s disease (AD) and dementia, APOEε4 , by hindering observation of a key, common genotype in humans - APOEε3/ε4 . Human studies are typically underpowered to address APOEε4 allele risk as the APOEε4/ε4 genotype is rare, which leaves human and mouse research unsupported to evaluate the APOEε3/ε4 genotype on molecular and pathological risk for AD and dementia.
Methods: As a part of MODEL-AD, we created and validated new versions of humanized APOEε3/ε3 and APOEε4/ε4 mouse strains that, due to unrestricted breeding, allow for the evaluation of the APOEε3/ε4 genotype. As biometric measures are often translatable between mouse and human, we profiled circulating lipid concentrations. We also performed transcriptional profiling of the cerebral cortex at 2 and 4 months (mos), comparing APOEε3/ε4 and APOEε4/ε4 to the reference APOEε3/ε3 using linear modeling and WGCNA. Further, APOE mice were exercised and compared to litter-matched sedentary controls, to evaluate the interaction between APOEε4 and exercise at a young age.
Results: Expression of human APOE isoforms were confirmed in APOEε3/ε3, APOEε3/ε4 and APOEε4/ε4 mouse brains. At two mos, cholesterol composition was influenced by sex, but not APOE genotype. Results show that the APOEε3/ε4 and APOEε4/ε4 genotype exert differential effects on cortical gene expression. APOEε3/ε4 uniquely impacts \u27hormone regulation\u27 and \u27insulin signaling,\u27 terms absent in APOEε4/ε4 data. At four mos, cholesterol and triglyceride levels were affected by sex and activity, with only triglyceride levels influenced by APOE genotype. Linear modeling revealed APOEε3/ε4 , but not APOEε4/ε4 , affected \u27extracellular matrix\u27 and \u27blood coagulation\u27 related terms. We confirmed these results using WGCNA, indicating robust, yet subtle, transcriptional patterns. While there was little evidence of APOE genotype by exercise interaction on the cortical transcriptome at this young age, running was predicted to affect myelination and gliogenesis, independent of APOE genotype with few APOE genotype-specific affects identified.
Discussion: APOEε4 allele dosage-specific effects were observed in circulating lipid levels and cortical transcriptional profiles. Future studies are needed to establish how these data may contribute to therapeutic development in APOEε3/ε4 and APOEε4/ε4 dementia patients
Experiment Simulation Configurations Used in DUNE CDR
The LBNF/DUNE CDR describes the proposed physics program and experimental
design at the conceptual design phase. Volume 2, entitled The Physics Program
for DUNE at LBNF, outlines the scientific objectives and describes the physics
studies that the DUNE collaboration will perform to address these objectives.
The long-baseline physics sensitivity calculations presented in the DUNE CDR
rely upon simulation of the neutrino beam line, simulation of neutrino
interactions in the far detector, and a parameterized analysis of detector
performance and systematic uncertainty. The purpose of this posting is to
provide the results of these simulations to the community to facilitate
phenomenological studies of long-baseline oscillation at LBNF/DUNE.
Additionally, this posting includes GDML of the DUNE single-phase far detector
for use in simulations. DUNE welcomes those interested in performing this work
as members of the collaboration, but also recognizes the benefit of making
these configurations readily available to the wider community.Comment: 9 pages, 4 figures, configurations in ancillary file
The promotion of local wellbeing: A primer for policymakers
There is growing interest among policymakers in the promotion of wellbeing as an
objective of public policy. In particular, local authorities have been given powers to
undertake action to promote wellbeing in their area. Recent advances in the academic
literature on wellbeing are giving rise to an increasingly detailed picture of the factors
that determine people’s subjective wellbeing (how they think and feel about their lives).
However, the concept of subjective wellbeing is poorly understood within local
government and much of the evidence base is extremely recent. I therefore review the
literature on the definition, measurement, and determinants of wellbeing, and discuss
some of its implications for local public policy
The Impact of Immersive Outdoor Activities in Local Woodlands on Young Carers Emotional Literacy and Well-Being
Children’s well-being is linked to a complex web of factors including the child’s personality, inherent protective mechanisms, family relationships, social capital, and economic status. Young carers are particularly at risk from poor mental health outcomes and low well-being. In this study the impact of immersive activities in nature on the well-being of 8 young carers (3 girls and 5 boys; aged 9–13 years) was explored. The immersive woodland activities included practical skills such as fire making, cooking, and using tools as well as team building and activities to help build trust. A mixed method, pre-test/post-test approach was undertaken using Emotional Literacy Checklists and interviews, poems and discussion. There were measurable improvements—specifically in motivation and self-awareness—in the young carers’ emotional literacy as reported by the parents and teachers. The well-being indicators that were referenced most frequently by parents and teachers related to the children’s social relationships and their development as individuals. The children reported changes related to social, physical, and “natural connection” well-being
Meox2 Haploinsufficiency Accelerates Axonal Degeneration in DBA/2J Glaucoma.
Purpose: Glaucoma is a complex disease with major risk factors including advancing age and increased intraocular pressure (IOP). Dissecting these earliest events will likely identify new avenues for therapeutics. Previously, we performed transcriptional profiling in DBA/2J (D2) mice, a widely used mouse model relevant to glaucoma. Here, we use these data to identify and test regulators of early gene expression changes in DBA/2J glaucoma.
Methods: Upstream regulator analysis (URA) in Ingenuity Pathway Analysis was performed to identify potential master regulators of differentially expressed genes. The function of one putative regulator, mesenchyme homeobox 2 (Meox2), was tested using a combination of genetic, biochemical, and immunofluorescence approaches.
Results: URA identified Meox2 as a potential regulator of early gene expression changes in the optic nerve head (ONH) of DBA/2J mice. Meox2 haploinsufficiency did not affect the characteristic diseases of the iris or IOP elevation seen in DBA/2J mice but did cause a significant increase in the numbers of eyes with axon damage compared to controls. While young mice appeared normal, aged Meox2 haploinsufficient DBA/2J mice showed a 44% reduction in MEOX2 protein levels. This correlated with modulation of age- and disease-specific vascular and myeloid alterations.
Conclusions: Our data support a model whereby Meox2 controls IOP-dependent vascular remodeling and neuroinflammation to promote axon survival. Promoting these earliest responses prior to IOP elevation may be a viable neuroprotective strategy to delay or prevent human glaucoma
Analysing Port Community System Network Evolution
Ports have played an important role in facilitating exchanges among countries since the day when inland transportation was poor. As ports become hubs for global supply chain, they have to maintain their competitiveness not only by reassuring their efficiency, reliability, accessibility to hinterland, and sustainability. In addition, there is a constant challenge from all operational parties of the port to acquire needed information or to trust information received, due to multiple legacy systems and platforms that do not integrate with each other, and to the lack of real time updates. There are differing agendas between parties and, sometimes, distrust within the multi-stakeholder ecosystem leads to working in silos. This jeopardises seamless data exchange and cooperation across the port value chain, resulting in significant inefficiencies. Port community system (PCS) can enhance communication and simplify administrative process resulting economic and environmental benefit for actors in the supply chain. The invisibility of the benefit, actors’ heterogeneity and significant investment to develop the system resulting a reluctance in implementing PCS. This chapter aims to study the evolution mechanism behind the process of PCS network development using lessons learned from industrial symbiosis network development and network trajectories theory. The PCS network development follows a serendipitous and goal-oriented process that can be categorised into three stages: pre-PCS network, PCS network emergence, and PCS network expansion. This chapter contributes to the exploration of network evolution and documents lesson learned to foster PCS implementation.© 2020 Springer. This is a post-peer-review, pre-copyedit version of an article published in European Port Cities in Transition: Moving Towards More Sustainable Sea Transport Hubs. The final authenticated version is available online at: http://dx.doi.org/10.1007/978-3-030-36464-9_10fi=vertaisarvioitu|en=peerReviewed
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