140 research outputs found
Critical Trapped Surfaces Formation in the Collision of Ultrarelativistic Charges in (A)dS
We study the formation of marginally trapped surfaces in the head-on
collision of two ultrarelativistic charges in space-time. The metric of
ultrarelativistic charged particles in is obtained by boosting
Reissner-Nordstr\"om space-time to the speed of light. We show that
formation of trapped surfaces on the past light cone is only possible when
charge is below certain critical - situation similar to the collision of two
ultrarelativistic charges in Minkowski space-time. This critical value depends
on the energy of colliding particles and the value of a cosmological constant.
There is richer structure of critical domains in case. In this case
already for chargeless particles there is a critical value of the cosmological
constant only below which trapped surfaces formation is possible. Appearance of
arbitrary small nonzero charge significantly changes the physical picture.
Critical effect which has been observed in the neutral case does not take place
more. If the value of the charge is not very large solution to the equation on
trapped surface exists for any values of cosmological radius and energy density
of shock waves. Increasing of the charge leads to decrease of the trapped
surface area, and at some critical point the formation of trapped surfaces of
the type mentioned above becomes impossible.Comment: 30 pages, Latex, 7 figures, Refs. added and typos correcte
Explicit de Sitter Flux Vacua for Global String Models with Chiral Matter
We address the open question of performing an explicit stabilisation of all
closed string moduli (including dilaton, complex structure and Kaehler moduli)
in fluxed type IIB Calabi-Yau compactifications with chiral matter. Using toric
geometry we construct Calabi-Yau manifolds with del Pezzo singularities.
D-branes located at such singularities can support the Standard Model gauge
group and matter content. In order to control complex structure moduli
stabilisation we consider Calabi-Yau manifolds which exhibit a discrete
symmetry that reduces the effective number of complex structure moduli. We
calculate the corresponding periods in the symplectic basis of invariant
three-cycles and find explicit flux vacua for concrete examples. We compute the
values of the flux superpotential and the string coupling at these vacua.
Starting from these explicit complex structure solutions, we obtain AdS and dS
minima where the Kaehler moduli are stabilised by a mixture of D-terms,
non-perturbative and perturbative alpha'-corrections as in the LARGE Volume
Scenario. In the considered example the visible sector lives at a dP_6
singularity which can be higgsed to the phenomenologically interesting class of
models at the dP_3 singularity.Comment: 49 pages, 5 figures; v2: references adde
Ten considerations for effectively managing the COVID-19 transition
Governments around the world have implemented measures to manage the transmission of coronavirus disease 2019 (COVID-19). While the majority of these measures are proving effective, they have a high social and economic cost, and response strategies are being adjusted. The World Health Organization (WHO) recommends that communities should have a voice, be informed and engaged, and participate in this transition phase. We propose ten considerations to support this principle: (1) implement a phased approach to a 'new normal'; (2) balance individual rights with the social good; (3) prioritise people at highest risk of negative consequences; (4) provide special support for healthcare workers and care staff; (5) build, strengthen and maintain trust; (6) enlist existing social norms and foster healthy new norms; (7) increase resilience and self-efficacy; (8) use clear and positive language; (9) anticipate and manage misinformation; and (10) engage with media outlets. The transition phase should also be informed by real-time data according to which governmental responses should be updated
A Novel Laser Vaccine Adjuvant Increases the Motility of Antigen Presenting Cells
Background
Development of a potent vaccine adjuvant without introduction of any side effects remains an unmet challenge in the field of the vaccine research.
Methodology/Principal Findings
We found that laser at a specific setting increased the motility of antigen presenting cells (APCs) and immune responses, with few local or systemic side effects. This laser vaccine adjuvant (LVA) effect was induced by brief illumination of a small area of the skin or muscle with a nondestructive, 532 nm green laser prior to intradermal (i.d.) or intramuscular (i.m.) administration of vaccines at the site of laser illumination. The pre-illumination accelerated the motility of APCs as shown by intravital confocal microscopy, leading to sufficient antigen (Ag)-uptake at the site of vaccine injection and transportation of the Ag-captured APCs to the draining lymph nodes. As a result, the number of Ag+ dendritic cells (DCs) in draining lymph nodes was significantly higher in both the 1° and 2° draining lymph nodes in the presence than in the absence of LVA. Laser-mediated increases in the motility and lymphatic transportation of APCs augmented significantly humoral immune responses directed against a model vaccine ovalbumin (OVA) or influenza vaccine i.d. injected in both primary and booster vaccinations as compared to the vaccine itself. Strikingly, when the laser was delivered by a hair-like diffusing optical fiber into muscle, laser illumination greatly boosted not only humoral but also cell-mediated immune responses provoked by i.m. immunization with OVA relative to OVA alone.
Conclusion/Significance
The results demonstrate the ability of this safe LVA to augment both humoral and cell-mediated immune responses. In comparison with all current vaccine adjuvants that are either chemical compounds or biological agents, LVA is novel in both its form and mechanism; it is risk-free and has distinct advantages over traditional vaccine adjuvants.National Institutes of Health (U.S.) (grant AI070785)National Institutes of Health (U.S.) (grant RC1 DA028378)Bill & Melinda Gates Foundation (Grand Challenges Explorations grant # 53273)Boston BioCom (Firm) (Sponsored Research agreement grant #2008A25652
Physics of Neutron Star Crusts
The physics of neutron star crusts is vast, involving many different research
fields, from nuclear and condensed matter physics to general relativity. This
review summarizes the progress, which has been achieved over the last few
years, in modeling neutron star crusts, both at the microscopic and macroscopic
levels. The confrontation of these theoretical models with observations is also
briefly discussed.Comment: 182 pages, published version available at
<http://www.livingreviews.org/lrr-2008-10
Genome Wide Association Study to predict severe asthma exacerbations in children using random forests classifiers
<p>Abstract</p> <p>Background</p> <p>Personalized health-care promises tailored health-care solutions to individual patients based on their genetic background and/or environmental exposure history. To date, disease prediction has been based on a few environmental factors and/or single nucleotide polymorphisms (SNPs), while complex diseases are usually affected by many genetic and environmental factors with each factor contributing a small portion to the outcome. We hypothesized that the use of random forests classifiers to select SNPs would result in an improved predictive model of asthma exacerbations. We tested this hypothesis in a population of childhood asthmatics.</p> <p>Methods</p> <p>In this study, using emergency room visits or hospitalizations as the definition of a severe asthma exacerbation, we first identified a list of top Genome Wide Association Study (GWAS) SNPs ranked by Random Forests (RF) importance score for the CAMP (Childhood Asthma Management Program) population of 127 exacerbation cases and 290 non-exacerbation controls. We predict severe asthma exacerbations using the top 10 to 320 SNPs together with age, sex, pre-bronchodilator FEV1 percentage predicted, and treatment group.</p> <p>Results</p> <p>Testing in an independent set of the CAMP population shows that severe asthma exacerbations can be predicted with an Area Under the Curve (AUC) = 0.66 with 160-320 SNPs in comparison to an AUC score of 0.57 with 10 SNPs. Using the clinical traits alone yielded AUC score of 0.54, suggesting the phenotype is affected by genetic as well as environmental factors.</p> <p>Conclusions</p> <p>Our study shows that a random forests algorithm can effectively extract and use the information contained in a small number of samples. Random forests, and other machine learning tools, can be used with GWAS studies to integrate large numbers of predictors simultaneously.</p
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Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson's disease on chromosome 7p15.3
Genome wide association studies (GWAS) for Parkinson's disease (PD) have previously revealed a significant association with a locus on chromosome 7p15.3, initially designated as the glycoprotein non-metastatic melanoma protein B (GPNMB) locus. In this study, the functional consequences of this association on expression were explored in depth by integrating different expression quantitative trait locus (eQTL) datasets (Braineac, CAGEseq, GTEx, and Phenotype-Genotype Integrator (PheGenI)). Top risk SNP rs199347 eQTLs demonstrated increased expressions of GPNMB, KLHL7, and NUPL2 with the major allele (AA) in brain, with most significant eQTLs in cortical regions, followed by putamen. In addition, decreased expression of the antisense RNA KLHL7-AS1 was observed in GTEx. Furthermore, rs199347 is an eQTL with long non-coding RNA (AC005082.12) in human tissues other than brain. Interestingly, transcript-specific eQTLs in immune-related tissues (spleen and lymphoblastoid cells) for NUPL2 and KLHL7-AS1 were observed, which suggests a complex functional role of this eQTL in specific tissues, cell types at specific time points. Significantly increased expression of GPNMB linked to rs199347 was consistent across all datasets, and taken in combination with the risk SNP being located within the GPNMB gene, these results suggest that increased expression of GPNMB is the causative link explaining the association of this locus with PD. However, other transcript eQTLs and subsequent functional roles cannot be excluded. This highlights the importance of further investigations to understand the functional interactions between the coding genes, antisense, and non-coding RNA species considering the tissue and cell-type specificity to understand the underlying biological mechanisms in PD
Investigating Tissue Optical Properties and Texture Descriptors of the Retina in Patients with Multiple Sclerosis
PURPOSE: To assess the differences in texture descriptors and optical properties of retinal tissue layers in patients with multiple sclerosis (MS) and to evaluate their usefulness in the detection of neurodegenerative changes using optical coherence tomography (OCT) image segmentation. PATIENTS AND METHODS: 38 patients with MS were examined using Stratus OCT. The raw macular OCT data were exported and processed using OCTRIMA software. The enrolled eyes were divided into two groups, based on the presence of optic neuritis (ON) in the history (MSON+ group, n = 36 and MSON- group, n = 31). Data of 29 eyes of 24 healthy subjects (H) were used as controls. A total of seven intraretinal layers were segmented and thickness as well as optical parameters such as contrast, fractal dimension, layer index and total reflectance were measured. Mixed-model ANOVA analysis was used for statistical comparisons. RESULTS: Significant thinning of the retinal nerve fiber layer (RNFL), ganglion cell/inner plexiform layer complex (GCL+IPL) and ganglion cell complex (GCC, RNFL+GCL+IPL) was observed between study groups in all comparisons. Significant difference was found in contrast in the RNFL, GCL+IPL, GCC, inner nuclear layer (INL) and outer plexiform layer when comparing MSON+ to the other groups. Higher fractal dimension values were observed in GCL+IPL and INL layers when comparing H vs. MSON+ groups. A significant difference was found in layer index in the RNFL, GCL+IPL and GCC layers in all comparisons. A significant difference was observed in total reflectance in the RNFL, GCL+IPL and GCC layers between the three examination groups. CONCLUSION: Texture and optical properties of the retinal tissue undergo pronounced changes in MS even without optic neuritis. Our results may help to further improve the diagnostic efficacy of OCT in MS and neurodegeneration
Prosociality in business: a human empowerment framework
This study introduces a human empowerment framework to better understand why some businesses are more socially oriented than others in their policies and activities. Building on Welzel’s theory of emancipation, we argue that human empowerment—comprised of four components: action resources, emancipative values, social movement activity, and civic entitlements—enables, motivates, and entitles individuals to pursue social goals for their businesses. Using a sample of over 15,000 entrepreneurs from 43 countries, we report strong empirical evidence for two ecological effects of the framework components on prosociality. We find that human empowerment (1) lifts entrepreneurs’ willingness to choose a social orientation for their business, and (2) reinforces the gender effect on prosociality in business activity. We discuss the human empowerment framework’s added value in understanding how modernization processes fully leverage the potential of social business activities for societies
Large Tandem, Higher Order Repeats and Regularly Dispersed Repeat Units Contribute Substantially to Divergence Between Human and Chimpanzee Y Chromosomes
Comparison of human and chimpanzee genomes has received much attention,
because of paramount role for understanding evolutionary step distinguishing us
from our closest living relative. In order to contribute to insight into Y
chromosome evolutionary history, we study and compare tandems, higher order
repeats (HORs), and regularly dispersed repeats in human and chimpanzee Y
chromosome contigs, using robust Global Repeat Map algorithm. We find a new
type of long-range acceleration, human-accelerated HOR regions. In peripheral
domains of 35mer human alphoid HORs, we find riddled features with ten
additional repeat monomers. In chimpanzee, we identify 30mer alphoid HOR. We
construct alphoid HOR schemes showing significant human-chimpanzee difference,
revealing rapid evolution after human-chimpanzee separation. We identify and
analyze over 20 large repeat units, most of them reported here for the first
time as: chimpanzee and human ~1.6 kb 3mer secondary repeat unit (SRU) and
~23.5 kb tertiary repeat unit (~0.55 kb primary repeat unit, PRU); human 10848,
15775, 20309, 60910, and 72140 bp PRUs; human 3mer SRU (~2.4 kb PRU); 715mer
and 1123mer SRUs (5mer PRU); chimpanzee 5096, 10762, 10853, 60523 bp PRUs; and
chimpanzee 64624 bp SRU (10853 bp PRU). We show that substantial
human-chimpanzee differences are concentrated in large repeat structures, at
the level of as much as ~70% divergence, sizably exceeding previous numerical
estimates for some selected noncoding sequences. Smeared over the whole
sequenced assembly (25 Mb) this gives ~14% human--chimpanzee divergence. This
is significantly higher estimate of divergence between human and chimpanzee
than previous estimates.Comment: 22 pages, 7 figures, 12 tables. Published in Journal of Molecular
Evolutio
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