1,770 research outputs found
Deploying Jupyter Notebooks at scale on XSEDE resources for Science Gateways and workshops
Jupyter Notebooks have become a mainstream tool for interactive computing in
every field of science. Jupyter Notebooks are suitable as companion
applications for Science Gateways, providing more flexibility and
post-processing capability to the users. Moreover they are often used in
training events and workshops to provide immediate access to a pre-configured
interactive computing environment. The Jupyter team released the JupyterHub web
application to provide a platform where multiple users can login and access a
Jupyter Notebook environment. When the number of users and memory requirements
are low, it is easy to setup JupyterHub on a single server. However, setup
becomes more complicated when we need to serve Jupyter Notebooks at scale to
tens or hundreds of users. In this paper we will present three strategies for
deploying JupyterHub at scale on XSEDE resources. All options share the
deployment of JupyterHub on a Virtual Machine on XSEDE Jetstream. In the first
scenario, JupyterHub connects to a supercomputer and launches a single node job
on behalf of each user and proxies back the Notebook from the computing node
back to the user's browser. In the second scenario, implemented in the context
of a XSEDE consultation for the IRIS consortium for Seismology, we deploy
Docker in Swarm mode to coordinate many XSEDE Jetstream virtual machines to
provide Notebooks with persistent storage and quota. In the last scenario we
install the Kubernetes containers orchestration framework on Jetstream to
provide a fault-tolerant JupyterHub deployment with a distributed filesystem
and capability to scale to thousands of users. In the conclusion section we
provide a link to step-by-step tutorials complete with all the necessary
commands and configuration files to replicate these deployments.Comment: 7 pages, 3 figures, PEARC '18: Practice and Experience in Advanced
Research Computing, July 22--26, 2018, Pittsburgh, PA, US
Epilepsy in older people
Globally, as populations age there will be challenges and opportunities to deliver optimal health care to senior citizens. Epilepsy, a condition characterised by spontaneous recurrent seizures, is common in older adults (aged >65 years) and yet has received comparatively little attention in this age group. In this Review, we evaluate the underlying causes of epilepsy in older people, explore difficulties in establishing a diagnosis of epilepsy in this population, discuss appropriate antiseizure medications, and evaluate potential surgical treatment options. We consider cognitive, psychological, and psychosocial comorbidities and the effect that epilepsy might have on an older person's broader social or care network in high-income versus middle-income and low-income countries. We emphasise the need for clinical trials to be more inclusive of older people with epilepsy to help inform therapeutic decision making and discuss whether measures to improve vascular risk factors might be an important strategy to reduce the probability of developing epilepsy
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Interdependence of Bad and Puma during Ionizing-Radiation-Induced Apoptosis
Ionizing radiation (IR)-induced DNA double-strand breaks trigger an extensive cellular signaling response that involves the coordination of hundreds of proteins to regulate DNA repair, cell cycle arrest and apoptotic pathways. The cellular outcome often depends on the level of DNA damage as well as the particular cell type. Proliferating zebrafish embryonic neurons are highly sensitive to IR-induced apoptosis, and both p53 and its transcriptional target puma are essential mediators of the response. The BH3-only protein Puma has previously been reported to activate mitochondrial apoptosis through direct interaction with the pro-apoptotic Bcl-2 family proteins Bax and Bak, thus constituting the role of an âactivatorâ BH3-only protein. This distinguishes it from BH3-only proteins like Bad that are thought to indirectly promote apoptosis through binding to anti-apoptotic Bcl-2 family members, thereby preventing the sequestration of activator BH3-only proteins and allowing them to directly interact with and activate Bax and Bak. We have shown previously that overexpression of the BH3-only protein Bad in zebrafish embryos supports normal embryonic development but greatly sensitizes developing neurons to IR-induced apoptosis. While Bad has previously been shown to play only a minor role in promoting IR-induced apoptosis of T cells in mice, we demonstrate that Bad is essential for robust IR-induced apoptosis in zebrafish embryonic neural tissue. Moreover, we found that both p53 and Puma are required for Bad-mediated radiosensitization in vivo. Our findings show the existence of a hierarchical interdependence between Bad and Puma whereby Bad functions as an essential sensitizer and Puma as an essential activator of IR-induced mitochondrial apoptosis specifically in embryonic neural tissue
Caries Epidemiology and Community Dentistry: Chances for Future Improvements in Caries Risk Groups. Outcomes of the ORCA Saturday Afternoon Symposium, Greifswald, 2014. Part 1
This paper reviews the first part of the outcomes of the ORCA Saturday Afternoon Symposium 2014 dealing with âcaries epidemiology and community dentistry: chances for future improvements in caries risk groups'. After the caries decline in many countries, there are remaining pockets of higher caries levels, mostly in the primary dentition and/or linked to a low socio-economic status (SES). The review into the evidence of caries-preventive measures clearly points to the use of fluorides, especially toothbrushing with fluoridated toothpaste and collective measures such as water fluoridation. In contrast to several unsuccessful high-risk approaches, community and public health programmes seem to be able to ensure a population-wide access and compliance in risk groups. Their simple and evidence-based measures mostly combine regular plaque removal and fluoride applications via toothbrushing, at least for children and adolescents. For the future, the common risk factor approach which addresses associations between oral health, social deprivation, diet, hygiene, smoking, alcohol use and stress should lead to combined efforts with other community health and education specialists. Further engagement with public policy, community leaders and administration is needed in order to strengthen healthy choices and behaviour, e.g. in âhealthy' schools and kindergartens. It seems advisable that these population programmes also aim at improving upstream factors
Targeting Fusion Proteins of HIV-1 and SARS-CoV-2
Viruses are disease-causing pathogenic agents that require host cells to replicate. Fusion of host and viral membranes is critical for the lifecycle of enveloped viruses. Studying viral fusion proteins can allow us to better understand how they shape immune responses and inform the design of therapeutics such as drugs, monoclonal antibodies, and vaccines. This thesis discusses two approaches to targeting two fusion proteins: Env from HIV-1 and S from SARS-CoV-2. The first chapter of this thesis is an introduction to viruses with a specific focus on HIV-1 CD4 mimetic drugs and antibodies against SARS-CoV-2. It discusses the architecture of these viruses and fusion proteins and how small molecules, peptides, and antibodies can target these proteins successfully to treat and prevent disease. In addition, a brief overview is included of the techniques involved in structural biology and how it has informed the study of viruses. For the interested reader, chapter 2 contains a review article that serves as a more in-depth introduction for both viruses as well as how the use of structural biology has informed the study of viral surface proteins and neutralizing antibody responses to them. The subsequent chapters provide a body of work divided into two parts. The first part in chapter 3 involves a study on conformational changes induced in the HIV-1 Env protein by CD4-mimemtic drugs using single particle cryo-EM. The second part encompassing chapters 4 and 5 includes two studies on antibodies isolated from convalescent COVID-19 donors. The former involves classification of antibody responses to the SARS-CoV-2 S receptor-binding domain (RBD). The latter discusses an anti-RBD antibody class that binds to a conserved epitope on the RBD and shows cross-binding and cross-neutralization to other coronaviruses in the sarbecovirus subgenus.</p
Electron dose calculations using the Method of Moments
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134898/1/mp7920.pd
Risk factors for dementia development, frailty, and mortality in older adults with epilepsy â A population-based analysis
Objective:
Although the prevalence of comorbid epilepsy and dementia is expected to increase, the impact is not well understood. Our objectives were to examine risk factors associated with incident dementia and the impact of frailty and dementia on mortality in older adults with epilepsy.
Methods:
The CALIBER scientific platform was used. People with incident epilepsy at or after age 65 were identified using Read codes and matched by age, sex, and general practitioner to a cohort without epilepsy (10:1). Baseline cohort characteristics were compared using conditional logistic regression models. Multivariate Cox proportional hazard regression models were used to examine the impact of frailty and dementia on mortality, and to assess risk factors for dementia development.
Results:
One thousand forty eight older adults with incident epilepsy were identified. The odds of having dementia at baseline were 7.39 [95% CI 5.21â10.50] times higher in older adults with epilepsy (nâŻ=âŻ62, 5.92%) compared to older adults without epilepsy (nâŻ=âŻ88, 0.86%). In the final multivariate Cox model (nâŻ=âŻ326), age [HR: 1.20, 95% CI 1.09â1.32], Charlson comorbidity index score [HR: 1.26, 95% CI 1.10â1.44], and sleep disturbances [HR: 2.41, 95% CI 1.07â5.43] at baseline epilepsy diagnosis were significantly associated with an increased hazard of dementia development over the follow-up period. In a multivariate Cox model (nâŻ=âŻ1047), age [HR: 1.07, 95% CI 1.03â1.11], baseline dementia [HR: 2.66, 95% CI 1.65â4.27] and baseline e-frailty index score [HR: 11.55, 95% CI 2.09â63.84] were significantly associated with a higher hazard of death among those with epilepsy. Female sex [HR: 0.77, 95% CI 0.59â0.99] was associated with a lower hazard of death.
Significance:
The odds of having dementia were higher in older adults with incident epilepsy. A higher comorbidity burden acts as a risk factor for dementia, while prevalent dementia and increasing frailty were associated with mortality
Patterns of variability of retinol levels in a harbour porpoise population from an unpolluted environment
Organochlorine compounds (OC) are known to induce vitamin A (retinoids) deficiency in mammals, which may be associated with impairment of immunocompetence, reproduction and growth. This makes retinoids a potentially useful biomarker of organochlorine impact on marine mammals. However, use of retinoids as a biomarker requires knowledge about its intrapopulation patterns of variation in natural conditions, information which is not currently available. We investigated these patterns in a cetacean population living in an unpolluted environment. 100 harbour porpoises Phocoena phocoena from West Greenland were sampled during the 1995 hunting season. Sex, age, morphometrics, nutritive condition, and retinol (following saponification) and OC levels in blubber were determined for each individual. OC levels found were extremely low and therefore considered unlikely to affect the population adversely: mean blubber concentrations, expressed on an extractable basis, were 2.04 (SD = 1.1) ppm for PCBs and 2.76 (SD = 1.66) ppm for tDDT. The mean blubber retinol concentration for the overall population was 59.66 (SD = 45.26) mu g g(-1). Taking into account the high contribution of blubber to body mass, blubber constitutes a significant body site for retinoid deposition in harbour porpoises. Retinol concentrations did not differ significantly between geographical regions or sexes, but they did correlate significantly (p <0.001) with age. Body condition, measured by determining the lipid content of the blubber, did not have a significant effect on retinol levels but the individuals examined were considered to be in an overall good nutritive condition. It is concluded that measurement of retinol concentrations in blubber samples is feasible and has a potential for use as a biomarker of organochlorine exposure in cetaceans. However, in order to do so, biological information, particularly age, is critical for the correct assessment of physiological impac
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