Escape times for rigid Brownian rotators in a bistable potential from the time evolution of the Green function and the characteristic time of the probability evolution

The greatest relaxation time for an assembly of three- dimensional rigid rotators in an axially symmetric bistable potential is obtained exactly in terms of continued fractions as a sum of the zero frequency decay functions (averages of the Legendre polynomials) of the system. This is accomplished by studying the entire time evolution of the Green function (transition probability) by expanding the time dependent distribution as a Fourier series and proceeding to the zero frequency limit of the Laplace transform of that distribution. The procedure is entirely analogous to the calculation of the characteristic time of the probability evolution (the integral of the configuration space probability density function with respect to the position co-ordinate) for a particle undergoing translational diffusion in a potential; a concept originally used by Malakhov and Pankratov (Physica A 229 (1996) 109). This procedure allowed them to obtain exact solutions of the Kramers one-dimensional translational escape rate problem for piecewise parabolic potentials. The solution was accomplished by posing the problem in terms of the appropriate Sturm-Liouville equation which could be solved in terms of the parabolic cylinder functions. The method (as applied to rotational problems and posed in terms of recurrence relations for the decay functions, i.e., the Brinkman approach c.f. Blomberg, Physica A 86 (1977) 49, as opposed to the Sturm-Liouville one) demonstrates clearly that the greatest relaxation time unlike the integral relaxation time which is governed by a single decay function (albeit coupled to all the others in non-linear fashion via the underlying recurrence relation) is governed by a sum of decay functions. The method is easily generalized to multidimensional state spaces by matrix continued fraction methods allowing one to treat non-axially symmetric potentials, where the distribution function is governed by two state variables. (C) 2001 Elsevier Science B.V. All rights reserved.

Surrogate-Based Optimization Using Multifidelity Models with Variable Parameterization and Corrected Space Mapping

Surrogate-based-optimization methods provide a means to achieve high-fidelity design optimization at reduced computational cost by using a high-fidelity model in combination with lower-fidelity models that are less expensive to evaluate. This paper presents a provably convergent trust-region model-management methodology for variableparameterization design models: that is, models for which the design parameters are defined over different spaces. Corrected space mapping is introduced as a method to map between the variable-parameterization design spaces. It is then used with a sequential-quadratic-programming-like trust-region method for two aerospace-related design optimization problems. Results for a wing design problem and a flapping-flight problem show that the method outperforms direct optimization in the high-fidelity space. On the wing design problem, the new method achieves 76% savings in high-fidelity function calls. On a bat-flight design problem, it achieves approximately 45% time savings, although it converges to a different local minimum than did the benchmark.

Two-stage mixed discrete-continuous identification of radial basis function (RBF) neural models for nonlinear systems

The identification of nonlinear dynamic systems using radial basis function (RBF) neural models is studied in this paper. Given a model selection criterion, the main objective is to effectively and efficiently build a parsimonious compact neural model that generalizes well over unseen data. This is achieved by simultaneous model structure selection and optimization of the parameters over the continuous parameter space. It is a mixed-integer hard problem, and a unified analytic framework is proposed to enable an effective and efficient two-stage mixed discrete-continuous; identification procedure. This novel framework combines the advantages of an iterative discrete two-stage subset selection technique for model structure determination and the calculus-based continuous optimization of the model parameters. Computational complexity analysis and simulation studies confirm the efficacy of the proposed algorithm.

Macronutrient balance mediates trade-offs between immune function and life history traits

1. Diet and health are intimately linked and recent studies have found that caloric restriction can affect immune function. However, when given a choice between diets that differ in their macronutrient composition, pathogen-infected individuals can select a diet that improves their survival, suggesting that the nutritional composition of the diet, as well as its calorie content, can play a role in defence against disease. Moreover, as individuals change their diet when infected, it suggests that a diet that is optimal for growth is not optimal for immunity, leading to trade-offs.
2. Currently, our knowledge of the effects of diet on immunity is limited because previous experiments have manipulated either single nutrients or the calorie content of the diet without considering their interactive effects. By simultaneously manipulating both the diet composition (quality) and its caloric density (quantity), in both naive and immune-challenged insects, we asked how do diet quality and quantity influence an individual's ability to mount an immune response? And to what extent are allocation trade-offs driven by quantity- versus quality-based constraints?
3. We restricted individuals to 20 diets varying in their protein and carbohydrate content and used 3D response surfaces to visualize dietary effects on larval growth and immune traits. Our results show that both constitutive and induced immune responses are not limited by the total quantity of nutrients consumed, but rather different traits respond differently to variation in the ratios of macronutrients (diet quality), and peak in different regions of macronutrient space. The preferred dietary composition therefore represents a compromise between the nutritional requirements of growth and immune responses. We also show that a non-pathogenic immune challenge does not affect diet choice, rather immune-challenged insects modify their allocation of nutrients to improve their immune response.
4. Our results indicate that immune traits are affected by the macronutrient content of the diet and that no diet can simultaneously optimize all components of the immune system. To date the emphasis has been on the effects of micronutrients in improving immunity, our findings indicate that this must be widened to include the neglected impact of macronutrients on defence against disease.

Exploratory Space-Time Analyses of Rift Valley Fever in South Africa in 2008-2011

Background: Rift Valley fever (RVF) is a zoonotic arbovirosis for which the primary hosts are domestic livestock (cattle, sheep and goats). RVF was first described in South Africa in 1950-1951. Mechanisms for short and long distance transmission have been hypothesised, but there is little supporting evidence. Here we describe RVF occurrence and spatial distribution in South Africa in 2008-11, and investigate the presence of a contagious process in order to generate hypotheses on the different mechanisms of transmission. Methodology/Principal Findings: A total of 658 cases were extracted from World Animal Health Information Database. Descriptive statistics, epidemic curves and maps were produced. The space-time K-function was used to test for evidence of space-time interaction. Five RVF outbreak waves (one in 2008, two in 2009, one in 2010 and one in 2011) of varying duration, location and size were reported. About 70% of cases (n = 471) occurred in 2010, when the epidemic was almost country-wide. No strong evidence of space-time interaction was found for 2008 or the second wave in 2009. In the first wave of 2009, a significant space-time interaction was detected for up to one month and over 40 km. In 2010 and 2011 a significant intense, short and localised space-time interaction (up to 3 days and 15 km) was detected, followed by one of lower intensity (up to 2 weeks and 35 to 90 km). Conclusions/Significance: The description of the spatiotemporal patterns of RVF in South Africa between 2008 and 2011 supports the hypothesis that during an epidemic, disease spread may be supported by factors other than active vector dispersal. Limitations of under-reporting and space-time K-function properties are discussed. Further spatial analyses and data are required to explain factors and mechanisms driving RVF spread. © 2012 Métras et al.

Efficient Architectural Design Space Exploration via Predictive Modeling

Efficiently exploring exponential-size architectural design spaces with many interacting parameters remains an open problem: the sheer number of experiments required renders detailed simulation intractable.We attack this via an automated approach that builds accurate predictive models. We simulate sampled points, using results to teach our models the function describing relationships among design parameters. The models can be queried and are very fast, enabling efficient design tradeoff discovery. We validate our approach via two uniprocessor sensitivity studies, predicting IPC with only 1–2% error. In an experimental study using the approach, training on 1% of a 250-K-point CMP design space allows our models to predict performance with only 4–5% error. Our predictive modeling combines well with techniques that reduce the time taken by each simulation experiment, achieving net time savings of three-four orders of magnitude.

Nonclassicality Criteria from Phase-Space Representations and Information-Theoretical Constraints Are Maximally Inequivalent

We consider two celebrated criteria for defining the nonclassicality of bipartite bosonic quantum systems, the first stemming from information theoretic concepts and the second from physical constraints on the quantum phase space. Consequently, two sets of allegedly classical states are singled out: (i) the set C composed of the so-called classical-classical (CC) states—separable states that are locally distinguishable and do not possess quantum discord; (ii) the set P of states endowed with a positive P representation (P-classical states)—mixtures of Glauber coherent states that, e.g., fail to show negativity of their Wigner function. By showing that C and P are almost disjoint, we prove that the two defining criteria are maximally inequivalent. Thus, the notions of classicality that they put forward are radically different. In particular, generic CC states show quantumness in their P representation, and vice versa, almost all P-classical states have positive quantum discord and, hence, are not CC. This inequivalence is further elucidated considering different applications of P-classical and CC states. Our results suggest that there are other quantum correlations in nature than those revealed by entanglement and quantum discord.

Liouville-space R-matrix-Floquet description of atomic radiative processes involving autoionizing states in the presence of intense electromagnetic fields

A reduced-density-operator description is developed for coherent optical phenomena in many-electron atomic systems, utilizing a Liouville-space, multiple-mode Floquet–Fourier representation. The Liouville-space formulation provides a natural generalization of the ordinary Hilbert-space (Hamiltonian) R-matrix-Floquet method, which has been developed for multi-photon transitions and laser-assisted electron–atom collision processes. In these applications, the R-matrix-Floquet method has been demonstrated to be capable of providing an accurate representation of the complex, multi-level structure of many-electron atomic systems in bound, continuum, and autoionizing states. The ordinary Hilbert-space (Hamiltonian) formulation of the R-matrix-Floquet method has been implemented in highly developed computer programs, which can provide a non-perturbative treatment of the interaction of a classical, multiple-mode electromagnetic field with a quantum system. This quantum system may correspond to a many-electron, bound atomic system and a single continuum electron. However, including pseudo-states in the expansion of the many-electron atomic wave function can provide a representation of multiple continuum electrons. The 'dressed' many-electron atomic states thereby obtained can be used in a realistic non-perturbative evaluation of the transition probabilities for an extensive class of atomic collision and radiation processes in the presence of intense electromagnetic fields. In order to incorporate environmental relaxation and decoherence phenomena, we propose to utilize the ordinary Hilbert-space (Hamiltonian) R-matrix-Floquet method as a starting-point for a Liouville-space (reduced-density-operator) formulation. To illustrate how the Liouville-space R-matrix-Floquet formulation can be implemented for coherent atomic radiative processes, we discuss applications to electromagnetically induced transparency, as well as to related pump–probe optical phenomena, and also to the unified description of radiative and dielectronic recombination in electron–ion beam interactions and high-temperature plasmas.

REDUCED ORDER MODELLING OF THE THERMAL BEHAVIOUR OF AN OFFICE SPACE

Reduced Order Models (ROMs) have proven to be a valid and efficient approach to model the thermal behaviour of building zones. The main issues associated with the use of zonal/lumped models are how to (1) divide the domain (lumps) and (2) evaluate the pa- rameters which characterise the lump-to-lump exchange of energy and momentum. The object of this research is to develop a methodology for the generation of ROMs from CFD models. The lumps of the ROM and their average property values are automatically ex- tracted from the CFD models through user defined constraints. This methodology has been applied to validated CFD models of a zone of the Environmental Research Insti- tute (ERI) Building in University College Cork (UCC). The ROM predicts temperature distribution in the domain with an average error lower than 2%. It is computationally efficient with an execution time of 3.45 seconds. Future steps in this research will be the development of the procedure to automatically extract the parameters which define lump-to-lump energy and momentum exchange. At the moment these parameters are evaluated through the minimisation of a cost function. The ROMs will also be utilised to predict the transient thermal behaviour of the building zone.

Regulating macrophage phenotype and function by retinal pigment epithelial cells

Purpose: We have shown previously that macrophages/microglia accumulate in the subretinal space and express CD68 and Arginase-1 in the aging eye. Subretinal macrophages are in close contact with retinal pigment epithelial (RPE) cells. We hypothesize that RPE cells may play an important role in regulating macrophage/microglial phenotype and function. The aim of this study was to investigate the effect of RPE cells on the phenotype and function of bone marrow–derived macrophages (BM-DMs).
Methods: BM-DM from C57BL/6J mice were cultured in DMEM supplemented with 20%L929 cell supernatant for 5 days. The phenotype of BM-DMs was confirmed by flow cytometry as CD11b+F4/80+. Primary RPE cells were cultured from C57BL/6J mice and confirmed by RPE65 and cytokeratin staining. BMDMs were co-cultured with different types of RPE cells (healthy, oxidized, and apoptotic RPE) and then isolated from the co-culture system for phenotypic and functional assays.
Results: Co-culture of BM-DMs with RPE cells results in a time-dependent down-regulation of MHC-II expression and the generation of CD11b+F4/80+Ly6G+ myeloid-derived suppressor cells (MDSC). qRT-PCR analysis showed that RPE-induced MDSCs expressed high levels of IL-6, IL-1β, and Arginase-1, but lower levels of IL-12p40 and TNF-a compared to naïve BM-DMs. The expression levels of iNOS, TGF-β and Ym1 did not differ 207 between naive BMDMs and RPE-induced MDSCs. Furthermore, functional studies showed that these cells had reduced phagocytic activity and lower ability to stimulate T cell activation and proliferation. When RPE cells were pre-treated with oxidized photoreceptor outer segments before co-culturing with BMDMs, the expression of IL-1β and IL-6 in BMDMs was increased whereas the expression of Arginase-1 was decreased. 
Conclusion: Our results suggest that healthy RPE cells can convert BMDMs into myeloid-derived suppressor cells under in vitro culture conditions, RPE-induced myeloid-derived suppressor cells are CD11b+F4/80+Ly6G+MHCIIlowIL6+IL1b+Arg-1+. The ability of RPE cells is reduced when suffering from oxidative insults.

Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation

Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g. chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged (∼2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders (Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation (FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intima–media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO₂^–) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3–4 (acute high altitude) and 12–14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders’ FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P = 0.004) and GTN-induced dilatation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2vs. 6.6 ± 0.3 m s⁻¹; P = 0.001). These changes persisted at days 12–14, and after allometrically scaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio (∼19%, P ≤ 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO₂^– increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilatation evident during acute (n = 11, r = −0.53) and chronic (n = 7, r = −0.69; P ≤ 0.01) exposure to 5050 m. In a follow-up, placebo-controlled experiment (n = 11 healthy lowlanders) conducted in a normobaric hypoxic chamber (inspired O₂ fraction () = 0.11; 6 h), a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7 ± 1.6 vs. 8.0 ±1.3%; P < 0.01); this decline in FMD was largely reversed following α₁-adrenoreceptor blockade. In conclusion, high-altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure, chronic high-altitude exposure appears to be associated with arterial remodelling.

Materials in extreme environments for energy, accelerators and space applications at ELI-NP.

As a leading facility in laser-driven nuclear physics, ELI-NP will develop innovative research in the fields of materials behavior in extreme environments and radiobiology, with applications in the development of accelerator components, new materials for next generation fusion and fission reactors, shielding solutions for equipment and human crew in long term space missions and new biomedical technologies. The specific properties of the laser-driven radiation produced with two lasers of 1 PW at a pulse repetition rate of 1 Hz each are an ultra-short time scale, a relatively broadband spectrum and the possibility to provide simultaneously several types of radiation. Complex, cosmic-like radiation will be produced in a ground-based laboratory allowing comprehensive investigations of their effects on materials and biological systems. The expected maximum energy and intensity of the radiation beams are 19 MeV with 10^9 photon/pulse for photon radiation, 2 GeV with 108 electron/pulse for electron beams, 60 MeV with 10^12 proton/pulse for proton and ion beams and 60 MeV with 107 neutron/pulse for a neutron source. Research efforts will be directed also towards measurements for radioprotection of the prompt and activated dose, as a function of laser and target characteristics and to the development and testing of various dosimetric methods and equipment.