Validation in agent-based models: an investigation on the CATS model

In this paper we deal with some validation experiments on the complex adaptive trivial system (CATS) model proposed in Gallegati et al. [Gallegati, M., Giulioni, G., Palestrini, A., Delli Gatti, D., 2003a. Financial fragility, patterns of firms’ entry and exit and aggregate dynamics. Journal of Economic Behavior and Organization 51, 79–97; Gallegati, M., Delli Gatti, D., Di Guilmi, C., Gaffeo, E., Giulioni, G., Palestrini, A., 2005. A new approach to business fluctuations: heterogeneous interacting agents, scaling laws and financial fragility. Journal of Economic Behavior and Organization 56, 489–512]. In particular starting from a sample of Italian firms included in the AIDA database, we perform several ex post validation experiments over the simulation period 1996–2001. In the experiments, the model parameters have been estimated using actual data and the initial set up consists of a sample of agents in 1996. The CATS model is then simulated over the period 1996–2001. Using alternative validation techniques, the simulations’ results are ex post validated respect to the actual data

The effect of prime-site occupancy on the hepatitis C virus NS3 protease structure.

We recently reported a new class of inhibitors of the chymotrypsin-like serine protease NS3 of the hepatitis C virus. These inhibitors exploit the binding potential of the S′ site of the protease, which is not generally used by the natural substrates. The effect of prime-site occupancy was analyzed by circular dichroism spectroscopy and limited proteolysis-mass spectrometry. Generally, nonprime inhibitors cause a structural change in NS3. Binding in the S′ site produces additional conformational changes with different binding modes, even in the case of the NS3/4A cofactor complex. Notably, inhibitor binding either in the S or S′ site also has profound effects on the stabilization of the protease. In addition, the stabilization propagates to regions not in direct contact with the inhibitor. In particular, the N-terminal region, which according to structural studies is endowed with low structural stability and is not stabilized by nonprime inhibitors, was now fully protected from proteolytic degradation. From the perspective of drug design, P-P′ inhibitors take advantage of binding pockets, which are not exploited by the natural HCV substrates; hence, they are an entry point for a novel class of NS3/4A inhibitors. Here we show that binding of each inhibitor is associated with a specific structural rearrangement. The development of a range of inhibitors belonging to different classes and an understanding of their interactions with the protease are required to address the issue of the most likely outcome of viral protease inhibitor therapy, that is, viral resistanc

Polyhedra in loop quantum gravity

Interwiners are the building blocks of spin-network states. The space of intertwiners is the quantization of a classical symplectic manifold introduced by Kapovich and Millson. Here we show that a theorem by Minkowski allows us to interpret generic configurations in this space as bounded convex polyhedra in Euclidean space: a polyhedron is uniquely described by the areas and normals to its faces. We provide a reconstruction of the geometry of the polyhedron: we give formulas for the edge lengths, the volume and the adjacency of its faces. At the quantum level, this correspondence allows us to identify an intertwiner with the state of a quantum polyhedron, thus generalizing the notion of quantum tetrahedron familiar in the loop quantum gravity literature. Moreover, coherent intertwiners result to be peaked on the classical geometry of polyhedra. We discuss the relevance of this result for loop quantum gravity. In particular, coherent spin-network states with nodes of arbitrary valence represent a collection of semiclassical polyhedra. Furthermore, we introduce an operator that measures the volume of a quantum polyhedron and examine its relation with the standard volume operator of loop quantum gravity. We also comment on the semiclassical limit of spinfoams with non-simplicial graphs.Comment: 32 pages, many figures. v2 minor correction

Spatiotemporal dynamics of single-letter reading: a combined ERP-FMRI study

This work investigates the neural correlates of single-letter reading by combining event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI), thus exploiting their complementary spatiotemporal resolutions. Three externally-paced reading tasks were administered with an event-related design: passive observation of letters and symbols and active reading aloud of letters. ERP and fMRI data were separately recorded from 8 healthy adults during the same experimental conditions. Due to the presence of artifacts in the EEG signals, two subjects were discarded from further analysis. Independent Component Analysis was applied to ERPs, after dimensionality reduction by Principal Component Analysis: some independent components were clearly related to specific reading functions and the associated current density distributions in the brain were estimated with Low Resolution Electromagnetic Tomography Analysis method (LORETA). The impulse hemodynamic response function was modeled as a linear combination of linear B-spline functions and fMRI statistical analysis was performed by multiple linear regression. fMRI and LORETA maps were superimposed in order to identify the overlapping activations and the activated regions specifically revealed by each modality. The results showed the existence of neuronal networks functionally specific for letter processing and for explicit verbal-motor articulation, including the temporo-parietal and frontal regions. Overlap between fMRI and LORETA results was observed in the inferior temporal-middle occipital gyrus, suggesting that this area has a crucial and multifunctional role for linguistic and reading processes, likely because its spatial location and strong interconnection with the main visual and auditory sensory systems may have favored its specialization in grapheme-phoneme matching

Exploring Holographic General Gauge Mediation

We study models of gauge mediation with strongly coupled hidden sectors, employing a hard wall background as an holographic dual description. The structure of the soft spectrum depends crucially on the boundary conditions one imposes on bulk fields at the IR wall. Generically, vector and fermion correlators have poles at zero momentum, leading to gauge mediation by massive vector messengers and/or generating Dirac gaugino masses. Instead, non-generic choices of boundary conditions let one cover all of GGM parameter space. Enriching the background with R-symmetry breaking scalars, the SSM soft term structure becomes more constrained and similar to previously studied top-down models, while retaining the more analytic control the present bottom-up approach offers.Comment: 28 pages, 4 figures; v2: typos corrected and refs adde

Cysteine oxidation targets peroxiredoxins 1 and 2 for exosomal release through a novel mechanism of redox-dependent secretion

Non-classical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of non-classical secretion. We have recently shown that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposure to inflammatory stimuli such as LPS or TNF-α. The released Prdx then acts to induce production of inflammatory cytokines. However, Prdx1 and 2 do not have signal peptides and therefore must be secreted by alternative mechanisms as has been postulated for the inflammatory mediators IL-1β and HMGB1. We show here that circulating Prdx1 and 2 are present exclusively as disulphide-linked homodimers. Inflammatory stimuli also induce in vitro release of Prdx1 and 2 as disulfide-linked homodimers. Mutation of cysteines Cys51 or Cys172 (but not Cys70) in Prdx2, and Cys52 or Cys173 (but not Cys71 or Cys83) in Prdx1 prevented dimer formation and this was associated with inhibition of their TNF-α-induced release. Thus, the presence and oxidation of key cysteine residues in these proteins are a prerequisite for their secretion in response to TNF-α and this release can be induced with an oxidant. In contrast, the secretion of the nuclear-associated danger signal HMGB1 is independent of cysteine oxidation, as shown by experiments with a cysteine-free HMGB1 mutant. Release of Prdx1 and 2 is not prevented by inhibitors of the classical secretory pathway; instead, both Prdx1 and 2 are released in exosomes from both HEK cells and monocytic cells. Serum Prdx1 and 2 are also associated with the exosomes. These results describe a novel pathway of protein secretion mediated by cysteine oxidation that underlines the importance of redox-dependent signalling mechanisms in inflammation

Children\u27s Health in Latin America: The Influence of Environmental Exposures

Background:Chronic diseases are increasing among children in Latin America. Objective and Methods:To examine environmental risk factors for chronic disease in LatinAmerican children and to develop a strategic initiative for control of these exposures, the WorldHealth Organization (WHO) including the Pan American Health Organization (PAHO), the Collegium Ramazzini, and Latin American scientists reviewed regional and relevant global data. Findings: Industrial development and urbanization are proceeding rapidly in Latin America and environmental pollution has become widespread. Environmental threats to children\u27s health include traditional hazards such as indoor air pollution and drinking water contamination; as well as the newer hazards of urban air pollution; toxic chemicals such as lead, asbestos, mercury,arsenic, and pesticides;hazardous and electronic waste;and climate change. The mix of traditional and modern hazards varies greatly across and within countries reflecting industrialization, urbanization and socioeconomic forces. Conclusions: To control environmental threats to children\u27s health in Latin America, WHO, including PAHO will focus on the most highly prevalent and serious hazards - indoor and outdoor air pollution, water pollution, and toxic chemicals. Strategies for controlling these hazards include developing tracking data on regional trends in children\u27s environmental health(CEH); building a network of Collaborating Centres; promoting biomedical research in CEH;building regional capacity; supporting development of evidence-based prevention policies; studying the economic costs of chronic diseases in children; and developing platforms for dialogue with relevant stakeholders.

Holographic renormalization and supersymmetry

Holographic renormalization is a systematic procedure for regulating divergences in observables in asymptotically locally AdS spacetimes. For dual boundary field theories which are supersymmetric it is natural to ask whether this defines a supersymmetric renormalization scheme. Recent results in localization have brought this question into sharp focus: rigid supersymmetry on a curved boundary requires specific geometric structures, and general arguments imply that BPS observables, such as the partition function, are invariant under certain deformations of these structures. One can then ask if the dual holographic observables are similarly invariant. We study this question in minimal N = 2 gauged supergravity in four and five dimensions. In four dimensions we show that holographic renormalization precisely reproduces the expected field theory results. In five dimensions we find that no choice of standard holographic counterterms is compatible with supersymmetry, which leads us to introduce novel finite boundary terms. For a class of solutions satisfying certain topological assumptions we provide some independent tests of these new boundary terms, in particular showing that they reproduce the expected VEVs of conserved charges.Comment: 70 pages; corrected typo

Holographic Correlators for General Gauge Mediation

We use holographic techniques to compute two-point functions of operators belonging to a conserved current supermultiplet in theories which break supersymmetry at strong coupling. These are the relevant quantities one has to compute in models of gauge mediation to determine the soft spectrum in supersymmetric extensions of the Standard Model (SSM). Such holographic approach can be used for diverse gravitational backgrounds, but here we focus, for definiteness, on asymptotically AdS backgrounds. After presenting the general framework, we apply our formulas to two explicit examples which differ by the nature of the SSM gauginos, which have Dirac or Majorana masses, corresponding to models that respectively preserve or break R-symmetry.Comment: 30 pages, 6 figures. v3: clarifications added, typos corrected, refs added, one figure improve

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group

OBJECTIVE: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. MATERIALS AND METHODS: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. RESULTS: Evidence from the selected studies were used to form evidence-based guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. CONCLUSIONS: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. HYPERCALCIURIA: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content 65 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. HYPEROXALURIA: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. HYPERURICOSURIA: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. HYPOCITRATURIA: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. CHILDREN: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein ( 3 liters/day) is strongly advised in children with cystinuria. ELDERLY: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved