1,240 research outputs found
Astrophysical Gyrokinetics: Basic Equations and Linear Theory
Magnetohydrodynamic (MHD) turbulence is encountered in a wide variety of
astrophysical plasmas, including accretion disks, the solar wind, and the
interstellar and intracluster medium. On small scales, this turbulence is often
expected to consist of highly anisotropic fluctuations with frequencies small
compared to the ion cyclotron frequency. For a number of applications, the
small scales are also collisionless, so a kinetic treatment of the turbulence
is necessary. We show that this anisotropic turbulence is well described by a
low frequency expansion of the kinetic theory called gyrokinetics. This paper
is the first in a series to examine turbulent astrophysical plasmas in the
gyrokinetic limit. We derive and explain the nonlinear gyrokinetic equations
and explore the linear properties of gyrokinetics as a prelude to nonlinear
simulations. The linear dispersion relation for gyrokinetics is obtained and
its solutions are compared to those of hot-plasma kinetic theory. These results
are used to validate the performance of the gyrokinetic simulation code {\tt
GS2} in the parameter regimes relevant for astrophysical plasmas. New results
on global energy conservation in gyrokinetics are also derived. We briefly
outline several of the problems to be addressed by future nonlinear
simulations, including particle heating by turbulence in hot accretion flows
and in the solar wind, the magnetic and electric field power spectra in the
solar wind, and the origin of small-scale density fluctuations in the
interstellar medium.Comment: emulateapj, 24 pages, 10 figures, revised submission to ApJ:
references added, typos corrected, reorganized and streamline
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An assessment of brain function predicts functional gains in a clinical stroke trial
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Predicting functional gains in a stroke trial.
A number of therapies in development for patients with central nervous system injury aim to reduce disability by improving function of surviving brain elements rather than by salvaging tissue. The current study tested the hypothesis that, after adjusting for a number of clinical assessments, a measure of brain function at baseline would improve prediction of behavioral gains after treatment.Twenty-four patients with chronic stroke underwent baseline clinical and functional MRI assessments, received 6 weeks of rehabilitation therapy with or without investigational motor cortex stimulation, and then had repeat assessments. Thirteen baseline clinical/radiological measures were evaluated for ability to predict subsequent trial-related gains.Across all patients, bivariate analyses found that greater trial-related functional gains were predicted by (1) smaller infarct volume, (2) greater baseline clinical status, and (3) lower degree of activation in stroke-affected motor cortex on baseline functional MRI. When these 3 variables were further assessed using multivariate linear regression modeling, only lower motor cortex activation and greater clinical status at baseline remained significant predictors. Note that lower baseline motor cortex activation was also associated with larger increases in motor cortex activation after treatment.Lower motor cortex activity at baseline predicted greater behavioral gains after therapy, even after controlling for a number of clinical assessments. The boosts in cortical activity that paralleled behavioral gains suggest that in some patients, low baseline cortical activity represents underuse of surviving cortical resources. A measure of brain function might be important for optimal clinical decision-making in the context of a restorative intervention
A Uniform Approximation for the Fidelity in Chaotic Systems
In quantum/wave systems with chaotic classical analogs, wavefunctions evolve
in highly complex, yet deterministic ways. A slight perturbation of the system,
though, will cause the evolution to diverge from its original behavior
increasingly with time. This divergence can be measured by the fidelity, which
is defined as the squared overlap of the two time evolved states. For chaotic
systems, two main decay regimes of either Gaussian or exponential behavior have
been identified depending on the strength of the perturbation. For perturbation
strengths intermediate between the two regimes, the fidelity displays both
forms of decay. By applying a complementary combination of random matrix and
semiclassical theory, a uniform approximation can be derived that covers the
full range of perturbation strengths. The time dependence is entirely fixed by
the density of states and the so-called transition parameter, which can be
related to the phase space volume of the system and the classical action
diffusion constant, respectively. The accuracy of the approximations are
illustrated with the standard map.Comment: 16 pages, 4 figures, accepted in J. Phys. A, special edition on
Random Matrix Theor
Raising the participation age in historical perspective : Policy learning from the past?
The raising of the participation age (RPA) to 17 in 2013 and 18 in 2015 marks a historic expansion of compulsory education. Despite the tendency of New Labour governments to eschew historical understanding and explanation, RPA was conceived with the benefit of an analysis of previous attempts to extend compulsion in schooling. This paper assesses the value of a historical understanding of education policy. The period from inception to the projected implementation of RPA is an extended one which has crossed over the change of government, from Labour to Coalition, in 2010. The shifting emphases and meanings of RPA are not simply technical issues but connect to profound historical and social changes. An analysis of the history of the raising of the school leaving age reveals many points of comparison with the contemporary situation. In a number of key areas it is possible to gain insights into the ways in which the study of the past can help to comprehend the present: the role of human capital, the structures of education, in curriculum development and in terms of preparations for change
Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer
Background: Previously we identified a DNA damage response–deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance.
Methods: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype. Isogenic cell lines, which represent DDRD-positive and -negative, were used to study the effects of chemokine release on peripheral blood mononuclear cell (PBMC) migration and the mechanism of immune signaling activation. Finally, we studied the association between the DDRD subtype and expression of the immune-checkpoint protein PD-L1 as detected by IHC. All statistical tests were two-sided.
Results: We found that DDRD breast tumors were associated with CD4+ and CD8+ lymphocytic infiltration (Fisher’s exact test P < .001) and that DDRD cells expressed the chemokines CXCL10 and CCL5 3.5- to 11.9-fold more than DNA damage response–proficient cells (P < .01). Conditioned medium from DDRD cells statistically significantly attracted PBMCs when compared with medium from DNA damage response–proficient cells (P < .05), and this was dependent on CXCL10 and CCL5. DDRD cells demonstrated increased cytosolic DNA and constitutive activation of the viral response cGAS/STING/TBK1/IRF3 pathway. Importantly, this pathway was activated in a cell cycle–specific manner. Finally, we demonstrated that S-phase DNA damage activated expression of PD-L1 in a STING-dependent manner.
Conclusions: We propose a novel mechanism of immune infiltration in DDRD tumors, independent of neoantigen production. Activation of this pathway and associated PD-L1 expression may explain the paradoxical lack of T-cell-mediated cytotoxicity observed in DDRD tumors. We provide a rationale for exploration of DDRD in the stratification of patients for immune checkpoint–based therapies
Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus
BACKGROUND: Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy.
METHODS AND RESULTS: Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed. Forty-eight percent and 24% of the perinatally HIV-infected adolescents had coronary arteries and abdominal aorta scores ≥1, representing increased cardiovascular disease risk factor burden. Significant predictors of coronary arteries scores ≥1 included male sex, history of an AIDS-defining condition, longer duration of use of a ritonavir-boosted protease inhibitor, and no prior use of tenofovir. Significant predictors of abdominal aorta scores ≥1 included suppressed viral load, history of an AIDS-defining condition, and longer duration of boosted protease inhibitor use. No significant changes in coronary arteries and abdominal aorta risk scores were observed over the 4-year study period.
CONCLUSIONS: A substantial proportion of perinatally HIV-infected youth have high PDAY scores, reflecting increased aggregate atherosclerotic cardiovascular disease risk factor burden. High scores were predicted by HIV disease severity and boosted protease inhibitor use. PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions
Physiological constraints dictate toxin spatial heterogeneity in snake venom glands
Background: Venoms are ecological innovations that have evolved numerous times, on each occasion accompanied by the co-evolution of specialised morphological and behavioural characters for venom production and delivery. The close evolutionary interdependence between these characters is exemplified by animals that control the composition of their secreted venom. This ability depends in part on the production of different toxins in different locations of the venom gland, which was recently documented in venomous snakes. Here, we test the hypothesis that the distinct spatial distributions of toxins in snake venom glands are an adaptation that enables the secretion of venoms with distinct ecological functions.
Results: We show that the main defensive and predatory peptide toxins are produced in distinct regions of the venom glands of the black-necked spitting cobra (Naja nigricollis), but these distributions likely reflect developmental effects. Indeed, we detected no significant differences in venom collected via defensive ‘spitting’ or predatory ‘biting’ events from the same specimens representing multiple lineages of spitting cobra. We also found the same spatial distribution of toxins in a non-spitting cobra and show that heterogeneous toxin distribution is a feature shared with a viper with primarily predatory venom.
Conclusions: Our findings suggest that heterogeneous distributions of toxins are not an adaptation to controlling venom composition in snakes. Instead, it likely reflects physiological constraints on toxin production by the venom glands, opening avenues for future research on the mechanisms of functional differentiation of populations of protein-secreting cells within adaptive contexts
Response to comment on 'Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity'
Lambert et al. question our retrospective and holistic epidemiological assessment of the role of chytridiomycosis in amphibian declines. Their alternative assessment is narrow and provides an incomplete evaluation of evidence. Adopting this approach limits understanding of infectious disease impacts and hampers conservation efforts. We reaffirm that our study provides unambiguous evidence that chytridiomycosis has affected at least 501 amphibian species
Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)
Background: The English National Health Service has made a major investment in nine partnerships between
higher education institutions and local health services called Collaborations for Leadership in Applied Health
Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and
implement research through sustained interactions between academics and health services. CLAHRCs provide a
natural ‘test bed’ for exploring questions about research implementation within a partnership model of delivery.
This protocol describes an externally funded evaluation that focuses on implementation mechanisms and
processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances.
Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which
deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see
it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual
framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to
Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth
comparative case studies of research implementation using multiple data collection methods including
interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of
data collection. We will test the wider applicability of emerging findings with a wider community using an
interpretative forum.
Discussion: The idea that collaboration between academics and services might lead to more applicable health
research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is
limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for
implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g.,
Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge
translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts
particularly with respect to integrated stakeholder involvement
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