2,020 research outputs found
Geometry of Policy Improvement
We investigate the geometry of optimal memoryless time independent decision
making in relation to the amount of information that the acting agent has about
the state of the system. We show that the expected long term reward, discounted
or per time step, is maximized by policies that randomize among at most
actions whenever at most world states are consistent with the agent's
observation. Moreover, we show that the expected reward per time step can be
studied in terms of the expected discounted reward. Our main tool is a
geometric version of the policy improvement lemma, which identifies a
polyhedral cone of policy changes in which the state value function increases
for all states.Comment: 8 page
Time-Domain Simulation of Mixed Nonlinear Magnetic and Electronic Systems
This paper describes a technique for the simulation of complex magnetic systems intimately connected to any necessary drive electronics. The system is split into two Kirchhoffian domains, one magnetic and one electric. Two-way interaction between the domains is supported by a virtual device called a magneto-electric differential gyrator. Using this technique, arbitrarily complex, non-linear, hysteretic magnetic systems may be simulated in the time domain, coupled to any appropriate non-linear electronics, at a fraction of the cost of a comparable finite element calculation. The capabilities of the system are demonstrated by the simulation of a feedback-controlled current sensing system, and the simulation tracks the measured behaviour of the system well outside its linear region, to the point that the non-linear hysteretic core is being driven into and out of saturation, a consequence of a time delay inherent in the electronics. This is compared with a simulation of the same system using a 'conventional' electronic simulation, and the increased accuracy of this technique clearly demonstrated
Vascular adaptation to exercise in humans: Role of hemodynamic stimuli
On the 400th anniversary of Harveyâs Lumleian lectures, this review focuses on âhemodynamicâ forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century discovery that endothelial cells modify arterial tone via paracrine transduction provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the interrelationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions, and the implications for human health. Exercise modifies blood flow, luminal shear stress, arterial pressure, and tangential wall stress, all of which can transduce changes in arterial function, diameter, and wall thickness. There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute to the well-established decrease in cardiovascular risk attributed to physical activity. © 2017 the American Physiological Society
The impact of low erythrocyte density in human blood on the fitness and energetic reserves of the African malaria vector Anopheles gambiae
Background
Anaemia is a common health problem in the developing world. This condition is characterized by a reduction in erythrocyte density, primarily from malnutrition and/or
infectious diseases such as malaria. As red blood cells are the primary source of protein for haematophagous mosquitoes, any reduction could impede the ability of mosquito vectors to transmit malaria by influencing their fitness or that of the parasites they transmit. The aim of this study was to determine the impact of differences in the density of red blood cells in human blood on malaria vector (Anopheles gambiae sensu stricto) fitness. The hypotheses tested are that mosquito vector energetic reserves and fitness are negatively influenced by reductions in the red cell density of host human blood meals commensurate with those expected from severe anaemia.
Methods
Mosquitoes (An. gambiae s.s.) were offered blood meals of different packed cell volume(PCV) of human blood consistent with those arising from severe anaemia (15%) and normalPCV (50%). Associations between mosquito energetic reserves (lipid, glucose and glycogen)and fitness measures (reproduction and survival) and blood meal PCV were investigated.
Results
The amount of protein that malaria vectors acquired from blood feeding (indexed by
haematin excretion) was significantly reduced at low blood PCV. However, mosquitoes
feeding on blood of low PCV had the same oviposition rates as those feeding on blood of normal PCV, and showed an increase in egg production of around 15%. The long-term survival of An. gambiae s.s was reduced after feeding on low PCV blood, but PCV had no significant impact on the proportion of mosquitoes surviving through the minimal period required to develop and transmit malaria parasites (estimated as 14 days post-blood feeding). The impact of blood PCV on the energetic reserves of mosquitoes was relatively minor.
Conclusions
These results suggest that feeding on human hosts whose PCV has been depleted due to severe anaemia does not significantly reduce the fitness or transmission potential of malaria vectors, and indicates that mosquitoes may be able exploit resources for reproduction more
efficiently from blood of low rather than normal PCV
Systematic review and meta-analysis of hepatitis C virus infection and HIV viral load: New insights into epidemiologic synergy
INTRODUCTION: Hepatitis C virus (HCV) and HIV infection frequently co-occur due to shared transmission routes. Co-infection is associated with higher HCV viral load (VL), but less is known about the effect of HCV infection on HIV VL and risk of onward transmission.
METHODS: We undertook a systematic review comparing 1) HIV VL among ART-naĂŻve, HCV co-infected individuals versus HIV mono-infected individuals and 2) HIV VL among treated versus untreated HCV co-infected individuals. We performed a random-effects meta-analysis and quantified heterogeneity using the I2 statistic. We followed Cochrane Collaboration guidelines in conducting our review and PRISMA guidelines in reporting results.
RESULTS AND DISCUSSION: We screened 3925 articles and identified 17 relevant publications. A meta-analysis found no evidence of increased HIV VL associated with HCV co-infection or between HIV VL and HCV treatment with pegylated interferon-alpha-2a/b and ribavirin.
CONCLUSIONS: This finding is in contrast to the substantial increases in HIV VL observed with several other systemic infections. It presents opportunities to elucidate the biological pathways that underpin epidemiological synergy in HIV co-infections and may enable prediction of which co-infections are most important to epidemic control
Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice
Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed ”CT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass
Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1
Aberrant transforming growth factorâÎČ (TGF-ÎČ) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-ÎČ signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-ÎČ signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-ÎČâinduced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment
Spontaneous R-Parity Violation, Flavor Symmetry and Tribimaximal Mixing
We explore the possibility of spontaneous R parity violation in the context
of flavor symmetry. Our model contains singlet matter chiral superfields which are arranged as triplet of
and as well as few additional Higgs chiral superfields which are singlet
under MSSM gauge group and belong to triplet and singlet representation under
the flavor symmetry. R parity is broken spontaneously by the vacuum
expectation values of the different sneutrino fields and hence we have
neutrino-neutralino as well as neutrino-MSSM gauge singlet higgsino mixings in
our model, in addition to the standard model neutrino- gauge singlet neutrino,
gaugino-higgsino and higgsino-higgsino mixings. Because all of these mixings we
have an extended neutral fermion mass matrix. We explore the low energy
neutrino mass matrix for our model and point out that with some specific
constraints between the sneutrino vacuum expectation values as well as the MSSM
gauge singlet Higgs vacuum expectation values, the low energy neutrino mass
matrix will lead to a tribimaximal mixing matrix. We also analyze the potential
minimization for our model and show that one can realize a higher vacuum
expectation value of the singlet
sneutrino fields even when the other sneutrino vacuum expectation values are
extremely small or even zero.Comment: 18 page
X-ray Absorption and Reflection in Active Galactic Nuclei
X-ray spectroscopy offers an opportunity to study the complex mixture of
emitting and absorbing components in the circumnuclear regions of active
galactic nuclei, and to learn about the accretion process that fuels AGN and
the feedback of material to their host galaxies. We describe the spectral
signatures that may be studied and review the X-ray spectra and spectral
variability of active galaxies, concentrating on progress from recent Chandra,
XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for
absorption covering a wide range of column densities, ionization and dynamics,
and discuss the growing evidence for partial-covering absorption from data at
energies > 10 keV. Such absorption can also explain the observed X-ray spectral
curvature and variability in AGN at lower energies and is likely an important
factor in shaping the observed properties of this class of source.
Consideration of self-consistent models for local AGN indicates that X-ray
spectra likely comprise a combination of absorption and reflection effects from
material originating within a few light days of the black hole as well as on
larger scales. It is likely that AGN X-ray spectra may be strongly affected by
the presence of disk-wind outflows that are expected in systems with high
accretion rates, and we describe models that attempt to predict the effects of
radiative transfer through such winds, and discuss the prospects for new data
to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58
pages, 9 figures. V2 has fixed an error in footnote
A branch and efficiency algorithm for the optimal design of supply chain networks
Supply chain operations directly affect service levels. Decision on amendment of facilities is generally decided based on overall cost, leaving out the efficiency of each unit. Decomposing the supply chain superstructure, efficiency analysis of the facilities (warehouses or distribution centers) that serve customers can be easily implemented. With the proposed algorithm, the selection of a facility is based on service level maximization and not just cost minimization as this analysis filters all the feasible solutions utilizing Data Envelopment Analysis (DEA) technique. Through multiple iterations, solutions are filtered via DEA and only the efficient ones are selected leading to cost minimization. In this work, the problem of optimal supply chain networks design is addressed based on a DEA based algorithm. A Branch and Efficiency (B&E) algorithm is deployed for the solution of this problem. Based on this DEA approach, each solution (potentially installed warehouse, plant etc) is treated as a Decision Making Unit, thus is characterized by inputs and outputs. The algorithm through additional constraints named âefficiency cutsâ, selects only efficient solutions providing better objective function values. The applicability of the proposed algorithm is demonstrated through illustrative examples
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