Altered cortical activation patterns associated with baroreflex unloading following 24 h of physical deconditioning

Cardiovascular arousal is associated with patterned cortical activity changes. Head-down-tilt bed rest (HDBR) dimishes the baroreflex-mediated cardiac control. The present study tested the hypothesis that HDBR deconditioning would modify the forebrain organization for heart rate (HR) control during baroreflex unloading. Heart rate variability (HRV), blood pressure and plasma hormones were analysed at rest, whereas HR and cortical autonomic activation patterns (functional magnetic resonance imaging) were measured during graded and randomly assigned lower body negative pressure treatments (LBNP, -15 and -35 mmHg) both before (Pre) and after (Post) a 24 h HDBR protocol (study 1; n= 8). An additional group was tested before and following diuretic-induced hypovolaemia (study 2; n= 9; spironolactone, 100 mg day-1 for 3 days) that mimicked the plasma volume lost during HDBR (-15% in both studies; P \u3c 0.05). Head-down bed rest with hypovolaemia did not affect baseline HR, mean arterial pressure, HRV or plasma catecholamines. Head-down bed rest augmented the LBNP-induced HR response (P \u3c 0.05), and this was associated with bed-rest-induced development of the following changes: (i) enhanced activation within the genual anterior cingulate cortex and the right anterior insular cortex; and (ii) deactivation patterns within the subgenual regions of the anterior cingulate cortex. Diuretic treatment (without HDBR) did not affect baseline HR and mean arterial pressure, but did reduce resting HRV and elevated circulating noradrenaline and plasma renin activity (P \u3c 0.05). The greater HR response to LBNP following diuretic (P \u3c 0.05) was associated with diminished activation of the right anterior insula. Our findings indicate that 24 h of HDBR minimized the impact of diuretic treatment on baseline autonomic and cardiovascular variables. The findings also indicate that despite the similar augmentation of HR responses to LBNP and despite similar pre-intervention cortical activation patterns, HDBR and diuretic treatment produced different effects on the cortical responses, with HDBR affecting anterior cingulate cortex and right insula regions, whereas diuretic treatment affected primarily the right insula alone, but in a direction that was opposite to HDBR. The data indicate that physical deconditioning can induce rapid functional changes within the cortical circuitry associated with baroreflex unloading, changes that are distinct from diuretic-induced hypovolaemia. The results suggest that physical activity patterns exert a rapid and notable impact on the cortical circuitry associated with cardiovascular control. © 2012 The Physiological Society

Control sideband generation for dual-recycled laser interferometric gravitational wave detectors

We present a discussion of the problems associated with generation of multiple control sidebands for length sensing and control of dual-recycled, cavity-enhanced Michelson interferometers and the motivation behind more complicated sideband generation methods. We focus on the Mach–Zehnder interferometer as a topological solution to the problem and present results from tests carried out at the Caltech 40 m prototype gravitational wave detector. The consequences for sensing and control for advanced interferometry are discussed, as are the implications for future interferometers such as Advanced LIGO

MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis.

BACKGROUND AND PURPOSE: The relationship between middle cerebral artery (MCA) flow velocity (CFV) and cerebral blood flow (CBF) is uncertain because of unknown vessel diameter response to physiological stimuli. The purpose of this study was to directly examine the effect of a simulated orthostatic stress (lower body negative pressure [LBNP]) as well as increased or decreased end-tidal carbon dioxide partial pressure (P(ET)CO(2)) on MCA diameter and CFV. METHODS: Twelve subjects participated in a CO(2) manipulation protocol and/or an LBNP protocol. In the CO(2) manipulation protocol, subjects breathed room air (normocapnia) or 6% inspired CO(2) (hypercapnia), or they hyperventilated to approximately 25 mm Hg P(ET)CO(2) (hypocapnia). In the LBNP protocol, subjects experienced 10 minutes each of -20 and -40 mm Hg lower body suction. CFV and diameter of the MCA were measured by transcranial Doppler and MRI, respectively, during the experimental protocols. RESULTS: Compared with normocapnia, hypercapnia produced increases in both P(ET)CO(2) (from 36+/-3 to 40+/-4 mm Hg, P CONCLUSIONS: Under the conditions of this study, changes in MCA diameter were not detected. Therefore, we conclude that relative changes in CFV were representative of changes in CBF during the physiological stimuli of moderate LBNP or changes in P(ET)CO(2)

Adaptive thermal compensation of test masses in advanced LIGO

As the first generation of laser interferometric gravitational wave detectors near operation, research and development has begun on increasing the instrument's sensitivity while utilizing the existing infrastructure. In the Laser Interferometer Gravitational Wave Observatory (LIGO), significant improvements are being planned for installation in ~2007, increasing strain sensitivity through improved suspensions and test mass substrates, active seismic isolation, and higher input laser power. Even with the highest quality optics available today, however, finite absorption of laser power within transmissive optics, coupled with the tremendous amount of optical power circulating in various parts of the interferometer, result in critical wavefront deformations which would cripple the performance of the instrument. Discussed is a method of active wavefront correction via direct thermal actuation on optical elements of the interferometer. A simple nichrome heating element suspended off the face of an affected optic will, through radiative heating, remove the gross axisymmetric part of the original thermal distortion. A scanning heating laser will then be used to remove any remaining non-axisymmetric wavefront distortion, generated by inhomogeneities in the substrate's absorption, thermal conductivity, etc. A proof-of-principle experiment has been constructed at MIT, selected data of which are presented.Comment: 11 pages, 7 figures, submitted to Classical and Quantum Gravit

Payments for Carbon Sequestration to Alleviate Development Pressure in a Rapidly Urbanizing Region

The purpose of this study was to determine individuals’ willingness to enroll in voluntary payments for carbon sequestration programs through the use of a discrete choice experiment delivered to forest owners living in the rapidly urbanizing region surrounding Charlotte, North Carolina. We examined forest owners’ willingness to enroll in payments for carbon sequestration policies under different levels of financial incentives (annual revenue), different contract lengths and different program administrators (e.g., private companies versus a state or federal agency). We also examined the influence forest owners’ sense of place had on their willingness to enroll in hypothetical programs. Our results showed a high level of ambivalence towards participating in payments for carbon sequestration programs. However, both financial incentives and contract lengths significantly influenced forest owners’ intent to enroll. Neither program administration nor forest owners’ sense of place influenced intent to enroll. While our analyses indicated payments from carbon sequestration programs are not currently competitive with the monetary returns expected from timber harvest or property sales, certain forest owners might see payments for carbon sequestration programs as a viable option for offsetting increasing tax costs as development encroaches and property values rise

Vascularization of the human intervertebral disc: A scoping review

Intervertebral discs (IVDs) are often referred to as the largest avascular structures of the human body, yet a collective resource characterizing the vascularization of the IVD does not exist. To address this gap, the objective of this study was to conduct a comprehensive search of the literature to review and summarize current knowledge of the prevalence and localization of blood supply in human IVDs, with a scoping review. A comprehensive search of peer-reviewed publications on the topic of IVD vascularization in humans was conducted across six electronic databases: PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and BIOSIS Previews. Studies of humans were included regardless of age, sex, ethnicity, and health status, with the exception of IVD herniation. Two independent reviewers screened titles and abstracts and full-texts according to eligibility criteria. The review was conducted and reported according to Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews guidelines. Our search yielded 3122 articles, with 22 articles meeting the inclusion criteria. The study samples ranged in age from fetal to \u3e90 years and included both sexes, various health statuses, and used different methodologies (eg, histology, medical imaging, and gross dissection) to assess vasculature. Overall, consistent observations were that (a) the nucleus pulposus of the IVD is avascular throughout life, (b) both the cartilage endplates and annulus fibrosus receive considerable blood supply early in life that diminishes over the lifespan, and (c) vascular ingrowth into the cartilage endplates and inner layers of the annulus fibrosus is commonly associated with damaged or disrupted tissue, irrespective of age. Histology and immunohistochemistry are often used to report vascularization of the IVD. The body of the current literature suggests that the IVD should not be generalized as an avascular tissue. Instead, vascularization of the IVD differs based on the constituent tissues, their age, and state of degeneration or damage

Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows

We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows. Finally, we discuss several major problems, including the occurrence of drug-resistant mutations, drug promiscuity, and the design of dual-effect inhibitors.Fil: Goncearenco, Alexander. National Institutes of Health; Estados UnidosFil: Li, Minghui. Soochow University; China. National Institutes of Health; Estados UnidosFil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Shoemaker, Benjamin A. National Institutes of Health; Estados UnidosFil: Panchenko, Anna R. National Institutes of Health; Estados Unido

Asymmetric WIMP dark matter

In existing dark matter models with global symmetries the relic abundance of dark matter is either equal to that of anti-dark matter (thermal WIMP), or vastly larger, with essentially no remaining anti-dark matter (asymmetric dark matter). By exploring the consequences of a primordial asymmetry on the coupled dark matter and anti-dark matter Boltzmann equations we find large regions of parameter space that interpolate between these two extremes. Interestingly, this new asymmetric WIMP framework can accommodate a wide range of dark matter masses and annihilation cross sections. The present-day dark matter population is typically asymmetric, but only weakly so, such that indirect signals of dark matter annihilation are not completely suppressed. We apply our results to existing models, noting that upcoming direct detection experiments will constrain a large region of the relevant parameter space.Comment: 32 pages, 6 figures, updated references, updated XENON100 bounds, typo in figure caption correcte

Beyond the Refugee Crisis how the UK news media represent asylum seekers across national boundaries

Migration is one of the most pressing, divisive issues in global politics today, and media play a crucial role in how communities understand and respond. This study examines how UK newspapers (n = 974) and popular news websites (n = 1044) reported on asylum seekers throughout 2017. It contributes to previous literature in two important ways. First, by examining the ‘new normal’ of daily news coverage in the wake of the 2015 ‘refugee crisis’ in Europe. Second, by looking at how asylum seekers from different regions are represented. The content analysis finds significant variations in how asylum seekers are reported, including terminology use and topics they are associated with. The paper also identifies important commonalities in how all asylum seekers are represented - most notably, the dominance of political elites as sources across all media content. It argues that Entman’s ‘cascade network model’ can help to explain this, with elites in one country able to influence transnational reports

Properties of Accretion Flows Around Coalescing Supermassive Black Holes

What are the properties of accretion flows in the vicinity of coalescing supermassive black holes (SBHs)? The answer to this question has direct implications for the feasibility of coincident detections of electromagnetic (EM) and gravitational wave (GW) signals from coalescences. Such detections are considered to be the next observational grand challenge that will enable testing general relativity in the strong, nonlinear regime and improve our understanding of evolution and growth of these massive compact objects. In this paper we review the properties of the environment of coalescing binaries in the context of the circumbinary disk and hot, radiatively inefficient accretion flow models and use them to mark the extent of the parameter space spanned by this problem. We report the results from an ongoing, general relativistic, hydrodynamical study of the inspiral and merger of black holes, motivated by the latter scenario. We find that correlated EM+GW oscillations can arise during the inspiral phase followed by the gradual rise and subsequent drop-off in the light curve at the time of coalescence. While there are indications that the latter EM signature is a more robust one, a detection of either signal coincidentally with GWs would be a convincing evidence for an impending SBH binary coalescence. The observability of an EM counterpart in the hot accretion flow scenario depends on the details of a model. In the case of the most massive binaries observable by the Laser Interferometer Space Antenna, upper limits on luminosity imply that they may be identified by EM searches out to z~0.1-1. However, given the radiatively inefficient nature of the gas flow, we speculate that a majority of massive binaries may appear as low luminosity AGN in the local universe.Comment: Revised version accepted to Class. Quantum Grav. for proceedings of 8th LISA Symposium. 15 pages, 3 figures, includes changes suggested in referee report