Turkish D-light : accentuating heritage values with daylight

Historic buildings have their own cultural identity, which is often related to their aesthetic qualities such as period characteristics (geometry, size, colour, form and shape), materials and construction. Daylight is one of the primary elements contributing to the distinctiveness of the visual environment of many historic buildings, but is rarely considered as one of the components that shape the character of a building when adaptive preservation schemes of historical buildings are planned. Many historic buildings were originally designed to accommodate activities different to their new use and preserving the quality of daylight that originally contributed to their visual identity is a challenging task. Maintaining the ‘day-lit appearance’ of a building can be particularly problematic if the building is to be used as a museum or a gallery owing to the artefacts’ conservation requirements. This work investigated the opportunities of maintaining the original ambient conditions of renovated historical buildings while meeting the required daylight levels of the proposed new use. The study utilised an annual daylight simulation method and hourly weather data to preserve daylight conditions in renovated historic buildings. The model was piloted in a Turkish bathhouse situated in Bursa, Turkey, that is currently under renovation. The simulation model produces 4483 hourly values of daylight illuminance for a period of a whole year using the computer program Radiance. It is concluded that daylight characteristics should be taken into account when developing a renovation scheme. With increasing pressure on valuing historic buildings in many parts of the world, the work reported here should be beneficial to those concerned with the conservation and adaptive reuse of historic buildings. The study findings could also be useful to those interested in predicting potential energy savings by combining daylighting and electric lighting in historic buildings

Runoff response of a small agricultural basin in the argentine Pampas considering connectivity aspects

Our manuscript analyses the surface runoff variability, and its controlling factors in a small basin with gentle slopes, at the headwaters of a flat catchment, to improve the knowledge of the hydrology of plain areas under agriculture. We study runoff, rainfall and antecedent conditions in the argentine Pampas region. We use correlations, regressions and quantitative and qualitative descriptive information of the system: erosion signs, ground cover by crops, groundwater depth data and temporal changes in the drainage network, to discuss and understand the complexity of the runoff process by frameworks to study (dis)connectivity. The analysis of 56 events evidenced a nonlinear rainfall–runoff relationship. In contrast with other works, we identified clear upper limit events, under which hydrological responses emerge, as a result of combinations of antecedent wetness, rainfall erosivity, ground cover and preferential drainage paths. We separated the nonlinear rainfall–runoff response in three linear relationships according to differences in antecedent wetness conditions. We found differences in runoff responses under wet and dry antecedent conditions, but complex responses under medium antecedent conditions. The analyses of the inputs, the structural and the functional elements of the (dis)connectivity frameworks, were key in the understanding of the temporal changes of runoff, and its complex responses. Temporal coincidences of connectivity components and their feedbacks appear to be strongly associated with the runoff dynamics. High-magnitude hydrological responses occur with complete coincidences, while partial coincidences between the components reduce connectivity and low magnitude and/or heterogeneous responses prevail. Thus, these analyses suggest that runoff is controlled by (dis)connectivity in this basin with gentle slopes. Our work contributes to the understanding of the process of surface runoff in the context of humid flatlands under agricultural land use, by the identification of the complex combinations of factors which regulate/control the (dis)connectivity that helps to interpret the nonlinearities of runoff.Fil: Ares, María Guadalupe. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff". - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff". - Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff"; ArgentinaFil: Varni, Marcelo Raúl. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff". - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff". - Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff"; ArgentinaFil: Chagas, Celio Ignacio. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Ingenieria Agricola y Uso de la Tierra. Cátedra de Manejo y Conservación de Suelo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Disturbance and Recovery of Salt Marsh Arthropod Communities following BP Deepwater Horizon Oil Spill

Oil spills represent a major environmental threat to coastal wetlands, which provide a variety of critical ecosystem services to humanity. The U.S. Gulf of Mexico is a hub of oil and gas exploration activities that historically have impacted intertidal habitats such as salt marsh. Following the BP Deepwater Horizon oil spill, we sampled the terrestrial arthropod community and marine invertebrates found in stands of Spartina alterniflora, the most abundant plant in coastal salt marshes. Sampling occurred in 2010 as oil was washing ashore and a year later in 2011. In 2010, intertidal crabs and terrestrial arthropods (insects and spiders) were suppressed by oil exposure even in seemingly unaffected stands of plants; however, Littoraria snails were unaffected. One year later, crab and arthropods had largely recovered. Our work is the first attempt that we know of assessing vulnerability of the salt marsh arthropod community to oil exposure, and it suggests that arthropods are both quite vulnerable to oil exposure and quite resilient, able to recover from exposure within a year if host plants remain healthy

Exercise training as S-Klotho protein stimulator in sedentary healthy adults: Rationale, design, and methodology

Aims: The secreted form of the α-Klotho gene (S-Klotho), which is considered a powerful biomarker of longevity, makes it an attractive target as an anti-ageing therapy against functional decline, sarcopenic obesity, metabolic and cardiovascular diseases, osteoporosis, and neurodegenerative disorders. The S-Klotho plasma levels could be related to physical exercise inasmuch physical exercise is involved in physiological pathways that regulate the SKlotho plasma levels. FIT-AGEING will determine the effect of different training modalities on the S-Klotho plasma levels (primary outcome) in sedentary healthy adults. FIT-AGEING will also investigate the physiological consequences of activating the klotho gene (secondary outcomes). Methods: FIT-AGEING will recruit 80 sedentary, healthy adults (50% women) aged 45–65 years old. Eligible participants will be randomly assigned to a non-exercise group, i.e. the control group, (n=20), a physical activity recommendation from World Health Organization group (n=20), a high intensity interval training group (n=20), and a whole-body electromyostimulation group (n=20). The laboratory measurements will be taken at the baseline and 12 weeks later including the S-Klotho plasma levels, physical fitness (cardiorespiratory fitness, muscular strength), body composition, basal metabolic rate, heart rate variability, maximal fat oxidation, health blood biomarkers, free-living physical activity, sleep habits, reaction time, cognitive variables, and health-related questionnaires. We will also obtain dietary habits data and cardiovascular disease risk factors.The study is supported by the Spanish Ministry of Education (FPU14/04172 and FPU15/03960). The study was partially supported by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES)

The Signaling Petri Net-Based Simulator: A Non-Parametric Strategy for Characterizing the Dynamics of Cell-Specific Signaling Networks

Reconstructing cellular signaling networks and understanding how they work are major endeavors in cell biology. The scale and complexity of these networks, however, render their analysis using experimental biology approaches alone very challenging. As a result, computational methods have been developed and combined with experimental biology approaches, producing powerful tools for the analysis of these networks. These computational methods mostly fall on either end of a spectrum of model parameterization. On one end is a class of structural network analysis methods; these typically use the network connectivity alone to generate hypotheses about global properties. On the other end is a class of dynamic network analysis methods; these use, in addition to the connectivity, kinetic parameters of the biochemical reactions to predict the network's dynamic behavior. These predictions provide detailed insights into the properties that determine aspects of the network's structure and behavior. However, the difficulty of obtaining numerical values of kinetic parameters is widely recognized to limit the applicability of this latter class of methods

Phosphoproteomics-Based Modeling Defines the Regulatory Mechanism Underlying Aberrant EGFR Signaling

BACKGROUND: Mutation of the epidermal growth factor receptor (EGFR) results in a discordant cell signaling, leading to the development of various diseases. However, the mechanism underlying the alteration of downstream signaling due to such mutation has not yet been completely understood at the system level. Here, we report a phosphoproteomics-based methodology for characterizing the regulatory mechanism underlying aberrant EGFR signaling using computational network modeling. METHODOLOGY/PRINCIPAL FINDINGS: Our phosphoproteomic analysis of the mutation at tyrosine 992 (Y992), one of the multifunctional docking sites of EGFR, revealed network-wide effects of the mutation on EGF signaling in a time-resolved manner. Computational modeling based on the temporal activation profiles enabled us to not only rediscover already-known protein interactions with Y992 and internalization property of mutated EGFR but also further gain model-driven insights into the effect of cellular content and the regulation of EGFR degradation. Our kinetic model also suggested critical reactions facilitating the reconstruction of the diverse effects of the mutation on phosphoproteome dynamics. CONCLUSIONS/SIGNIFICANCE: Our integrative approach provided a mechanistic description of the disorders of mutated EGFR signaling networks, which could facilitate the development of a systematic strategy toward controlling disease-related cell signaling

Simulation of Postsynaptic Glutamate Receptors Reveals Critical Features of Glutamatergic Transmission

Activation of several subtypes of glutamate receptors contributes to changes in postsynaptic calcium concentration at hippocampal synapses, resulting in various types of changes in synaptic strength. Thus, while activation of NMDA receptors has been shown to be critical for long-term potentiation (LTP) and long term depression (LTD) of synaptic transmission, activation of metabotropic glutamate receptors (mGluRs) has been linked to either LTP or LTD. While it is generally admitted that dynamic changes in postsynaptic calcium concentration represent the critical elements to determine the direction and amplitude of the changes in synaptic strength, it has been difficult to quantitatively estimate the relative contribution of the different types of glutamate receptors to these changes under different experimental conditions. Here we present a detailed model of a postsynaptic glutamatergic synapse that incorporates ionotropic and mGluR type I receptors, and we use this model to determine the role of the different receptors to the dynamics of postsynaptic calcium with different patterns of presynaptic activation. Our modeling framework includes glutamate vesicular release and diffusion in the cleft and a glutamate transporter that modulates extracellular glutamate concentration. Our results indicate that the contribution of mGluRs to changes in postsynaptic calcium concentration is minimal under basal stimulation conditions and becomes apparent only at high frequency of stimulation. Furthermore, the location of mGluRs in the postsynaptic membrane is also a critical factor, as activation of distant receptors contributes significantly less to calcium dynamics than more centrally located ones. These results confirm the important role of glutamate transporters and of the localization of mGluRs in postsynaptic sites in their signaling properties, and further strengthen the notion that mGluR activation significantly contributes to postsynaptic calcium dynamics only following high-frequency stimulation. They also provide a new tool to analyze the interactions between metabotropic and ionotropic glutamate receptors

Modeling and Analysis of the Molecular Basis of Pain in Sensory Neurons

Intracellular calcium dynamics are critical to cellular functions like pain transmission. Extracellular ATP plays an important role in modulating intracellular calcium levels by interacting with the P2 family of surface receptors. In this study, we developed a mechanistic mathematical model of ATP-induced P2 mediated calcium signaling in archetype sensory neurons. The model architecture, which described 90 species connected by 162 interactions, was formulated by aggregating disparate molecular modules from literature. Unlike previous models, only mass action kinetics were used to describe the rate of molecular interactions. Thus, the majority of the 252 unknown model parameters were either association, dissociation or catalytic rate constants. Model parameters were estimated from nine independent data sets taken from multiple laboratories. The training data consisted of both dynamic and steady-state measurements. However, because of the complexity of the calcium network, we were unable to estimate unique model parameters. Instead, we estimated a family or ensemble of probable parameter sets using a multi-objective thermal ensemble method. Each member of the ensemble met an error criterion and was located along or near the optimal trade-off surface between the individual training data sets. The model quantitatively reproduced experimental measurements from dorsal root ganglion neurons as a function of extracellular ATP forcing. Hypothesized architecture linking phosphoinositide regulation with P2X receptor activity explained the inhibition of P2X-mediated current flow by activated metabotropic P2Y receptors. Sensitivity analysis using individual and the whole system outputs suggested which molecular subsystems were most important following P2 activation. Taken together, modeling and analysis of ATP-induced P2 mediated calcium signaling generated qualitative insight into the critical interactions controlling ATP induced calcium dynamics. Understanding these critical interactions may prove useful for the design of the next generation of molecular pain management strategies

A Kinetic Model of Dopamine- and Calcium-Dependent Striatal Synaptic Plasticity

Corticostriatal synapse plasticity of medium spiny neurons is regulated by glutamate input from the cortex and dopamine input from the substantia nigra. While cortical stimulation alone results in long-term depression (LTD), the combination with dopamine switches LTD to long-term potentiation (LTP), which is known as dopamine-dependent plasticity. LTP is also induced by cortical stimulation in magnesium-free solution, which leads to massive calcium influx through NMDA-type receptors and is regarded as calcium-dependent plasticity. Signaling cascades in the corticostriatal spines are currently under investigation. However, because of the existence of multiple excitatory and inhibitory pathways with loops, the mechanisms regulating the two types of plasticity remain poorly understood. A signaling pathway model of spines that express D1-type dopamine receptors was constructed to analyze the dynamic mechanisms of dopamine- and calcium-dependent plasticity. The model incorporated all major signaling molecules, including dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP32), as well as AMPA receptor trafficking in the post-synaptic membrane. Simulations with dopamine and calcium inputs reproduced dopamine- and calcium-dependent plasticity. Further in silico experiments revealed that the positive feedback loop consisted of protein kinase A (PKA), protein phosphatase 2A (PP2A), and the phosphorylation site at threonine 75 of DARPP-32 (Thr75) served as the major switch for inducing LTD and LTP. Calcium input modulated this loop through the PP2B (phosphatase 2B)-CK1 (casein kinase 1)-Cdk5 (cyclin-dependent kinase 5)-Thr75 pathway and PP2A, whereas calcium and dopamine input activated the loop via PKA activation by cyclic AMP (cAMP). The positive feedback loop displayed robust bi-stable responses following changes in the reaction parameters. Increased basal dopamine levels disrupted this dopamine-dependent plasticity. The present model elucidated the mechanisms involved in bidirectional regulation of corticostriatal synapses and will allow for further exploration into causes and therapies for dysfunctions such as drug addiction

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s=7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb(-1) of root s = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved