Uncovering a role for micro-RNAs in sleep homeostasis and energy metabolism

Micro-RNAs (miRNAs) are key, post-transcriptional regulators of gene expression and have been implicated in almost every cellular process investigated thus far. However, their role in sleep, in particular the homeostatic aspect of sleep control, has received little attention. We here assessed the effects of sleep deprivation on the brain miRNA transcriptome in the mouse. Sleep deprivation affected miRNA expression in a brain-region specific manner. The forebrain expression of the miRNA miR-709 was affected the most and in situ analyses confirmed its robust increase throughout the brain, especially in the cerebral cortex and the hippocampus. The hippocampus was a major target of the sleep deprivation affecting 37 miRNAs compared to 52 in the whole forebrain. Moreover, independent from the sleep deprivation condition, miRNA expression was highly region-specific with 45% of all expressed miRNAs showing higher expression in hippocampus and 55% in cortex. Next we demonstrated that down-regulation of miRNAs in Com/c2o-expressing neurons of adult mice, through a conditional and inducible Dicer knockout mice model (cKO), results in an altered homeostatic response after sleep deprivation eight weeks following the tamoxifen-induced recombination. Dicer cKO mice showed a larger increase in the electro-encephalographic (EEG) marker of sleep pressure, EEG delta power, and a reduced Rapid Eye Movement sleep rebound, compared to controls, highlighting a functional role of miRNAs in sleep homeostasis. Beside a sleep phenotype, Dicer cKO mice developed an unexpected, severe obesity phenotype associated with hyperphagia and altered metabolism. Even more surprisingly, after reaching maximum body weight 5 weeks after tamoxifen injection, obese cKO mice spontaneously started losing weight as rapidly as it was gained. Brain transcriptome analyses in obese mice identified several obesity-related pathways (e.g. leptin, somatostatin, and nemo-like kinase signaling), as well as genes involved in feeding and appetite (e.g. Pmch, Neurotensin). A gene cluster with anti-correlated expression in the cerebral cortex of post-obese compared to obese mice was enriched for synaptic plasticity pathways. While other studies have identified a role for miRNAs in obesity, we here present a unique model that allows for the study of processes involved in reversing obesity. Moreover, our study identified the cortex as a brain area important for body weight homeostasis. Together, these observations strongly suggest a role for miRNAs in the maintenance of homeostatic processes in the mouse, and support the hypothesis of a tight relationship between sleep and metabolism at a molecular - Les micro-ARNS (miARNs) sont des r��gulateurs post-transcriptionnels de l'expression des g��nes, impliqu��s dans la quasi-totalit�� des processus cellulaires. Cependant, leur r��le dans la r��gulation du sommeil, et en particulier dans le maintien de l'hom��ostasie du sommeil, n'a re��u que tr��s peu d'attention jusqu'�� pr��sent. Dans cette ��tude, nous avons ��tudi�� les cons��quences d'une privation de sommeil sur l'expression c��r��brale des miARNs chez la souris, et observ�� des changements dans l'expression de nombreux miARNs. Dans le cerveau ant��rieur, miR-709 est le miARN le plus affect�� par la perte de sommeil, en particulier dans le cortex c��r��bral et l'hippocampe. L'hippocampe est la r��gion la plus touch��e avec 37 miARNs chang��s compar��s �� 52 dans le cerveau entier. Par ailleurs, ind��pendamment de la privation de sommeil, certains miARNs sont sp��cifiquement enrichis dans certaines aires c��r��brales, 45% des miARNs ��tant surexprim��s dans l'hippocampe contre 55% dans le cortex. Dans une seconde ��tude, nous avons observ�� que la d��l��tion de DICER, enzyme essentielle �� la biosynth��se des miARNs, et la perte subs��quente des miARNs dans les neurones exprimant la prot��ine CAMK2a alt��re la r��ponse hom��ostatique �� une privation de sommeil, 8 semaines apr��s l'induction de la recombinaison g��n��tique par le tamoxifen. Les souris sans Dicer (cKO) ont une plus large augmentation de l'EEG delta power, le principal marqueur ��lectro-enc��phalographique du besoin de sommeil, compar��e aux contr��les, ainsi qu'un rebond en sommeil paradoxal plus petit. De fa��on surprenante, les souris Dicer cKO d��veloppent une ob��sit�� rapide, s��v��re et transitoire, associ��e �� de l'hyperphagie et une alt��ration de leur m��tabolisme ��nerg��tique. Apr��s avoir atteint un pic maximal d'ob��sit��, les souris cKO entrent spontan��ment dans une p��riode de perte de poids rapide. L'analyse du transcriptome c��r��bral des souris ob��ses nous a permis d'identifier des voies associ��es �� l'ob��sit�� (leptine, somatostatine et nemo-like kinase), et �� la prise alimentaire (Pmch, Neurotensin), tandis que celui des souris post-ob��ses a r��v��l�� un groupe de g��nes li��s �� la plasticit�� synaptique. Au-del�� des nombreux mod��les d'ob��sit�� existant chez la souris, notre ��tude pr��sente un mod��le unique permettant d'��tudier les m��canismes sous-jacent la perte de poids. De plus, nous avons mis en ��vidence un r��le important du cortex c��r��bral dans le maintien de la balance ��nerg��tique. En conclusion, toutes ces observations soutiennent l'id��e que les miARNs sont des r��gulateurs cruciaux dans le maintien des processus hom��ostatiques et confortent l'hypoth��se d'une ��troite relation mol��culaire entre le sommeil et le m��tabolisme.

Biophysical requirements of power-supply systems: nuclear energy and fossil energy

The report presents a grammar capable of analyzing the process of production of electricity in modular elements for different power-supply systems, defined using semantic and formal categories. In this way it becomes possible to individuate similarities and differences in the process of production of electricity, and then measure and compare ���apples��� with ���apples��� and ���oranges��� with ���oranges���. For instance, when comparing the various unit operations of the process of production of electricity with nuclear energy to the analogous unit operations of the process of production of fossil energy, we see that the various phases of the process are the same. The only difference is related to characteristics of the process associated with the generation of heat which are completely different in the two systems. As a matter of facts, the performance of the production of electricity from nuclear energy can be studied, by comparing the biophysical costs associated with the different unit operations taking place in nuclear and fossil power plants when generating process heat or net electricity. By adopting this approach, it becomes possible to compare the performance of the two power-supply systems by comparing their relative biophysical requirements for the phases that both nuclear energy power plants and fossil energy power plants have in common: (i) mining; (ii) refining/enriching; (iii) generating heat/electricity; (iv) handling the pollution/radioactive wastes. This report presents the evaluation of the biophysical requirements for the two powersupply systems: nuclear energy and fossil energy. In particular, the report focuses on the following requirements: (i) electricity; (ii) fossil-fuels, (iii) labor; and (iv) materials.

Debris flow hazard modelling on medium scale: Valtellina di Tirano, Italy

Debris flow hazard modelling at medium (regional) scale has been subject of various studies in recent years. In this study, hazard zonation was carried out, incorporating information about debris flow initiation probability (spatial and temporal), and the delimitation of the potential runout areas. Debris flow hazard zonation was carried out in the area of the Consortium of Mountain Municipalities of Valtellina di Tirano (Central Alps, Italy). The complexity of the phenomenon, the scale of the study, the variability of local conditioning factors, and the lacking data limited the use of process-based models for the runout zone delimitation. Firstly, a map of hazard initiation probabilities was prepared for the study area, based on the available susceptibility zoning information, and the analysis of two sets of aerial photographs for the temporal probability estimation. Afterwards, the hazard initiation map was used as one of the inputs for an empirical GIS-based model (Flow-R), developed at the University of Lausanne (Switzerland). An estimation of the debris flow magnitude was neglected as the main aim of the analysis was to prepare a debris flow hazard map at medium scale. A digital elevation model, with a 10 m resolution, was used together with landuse, geology and debris flow hazard initiation maps as inputs of the Flow-R model to restrict potential areas within each hazard initiation probability class to locations where debris flows are most likely to initiate. Afterwards, runout areas were calculated using multiple flow direction and energy based algorithms. Maximum probable runout zones were calibrated using documented past events and aerial photographs. Finally, two debris flow hazard maps were prepared. The first simply delimits five hazard zones, while the second incorporates the information about debris flow spreading direction probabilities, showing areas more likely to be affected by future debris flows. Limitations of the modelling arise mainly from the models applied and analysis scale, which are neglecting local controlling factors of debris flow hazard. The presented approach of debris flow hazard analysis, associating automatic detection of the source areas and a simple assessment of the debris flow spreading, provided results for consequent hazard and risk studies. However, for the validation and transferability of the parameters and results to other study areas, more testing is needed.

Quantization of energy and writhe in self-repelling knots

Probably the most natural energy functional to be considered for knotted strings is that given by electrostatic repulsion. In the absence of counter-charges, a charged, knotted string evolving along the energy gradient of electrostatic repulsion would progressively tighten its knotted domain into a point on a perfectly circular string. However, in the presence of charge screening self-repelling knotted strings can be stabilized. It is known that energy functionals in which repulsive forces between repelling charges grow inversely proportionally to the third or higher power of their relative distance stabilize self-repelling knots. Especially interesting is the case of the third power since the repulsive energy becomes scale invariant and does not change upon Mobius transformations (reflections in spheres) of knotted trajectories. We observe here that knots minimizing their repulsive Mobius energy show quantization of the energy and writhe (measure of chirality) within several tested families of knots.

International regimes as knowledge syndicates? Energy and trends of global governance

El poder de l'Estat i la sobirania tradicional s'est�� deteriorant de manera constant, sobretot en termes de la provisi�� de certs b��ns p��blics fonamentals. Els Estats, en particular, s��n incapa��os de manejar el coneixement i la informaci�� que ��s essencial per mantenir la competitivitat i la sostenibilitat en una economia interdependent. Estructures fiables de la governan��a mundial i la cooperaci�� internacional estan lluny de ser establertes. Energia com a problema a les agendes p dels governs, les empreses privades i la societat civil ��s un exemple manifest d'aquesta din��mica.. L'actual sistema de governan��a mundial d'energia implica accions pol��tiques disperses per actors divers. L'Ag��ncia Internacional de l'Energia t�� un paper destacat, per�� est�� debilitat per la seva composici�� limitada i basada en el coneixement- epist��mic en lloc del material o executiu. Aquest treball sost�� que ni la mida ni nombre de membres disponibles estan dificultant la governabilitat mundial d'energia. M��s aviat, l'energia ��s una s��rie de b��ns p��blics que es troben als llimbs, on els estats no poden pagar la seva disposici��, aix�� com els diversos interessos impedir l'establiment d'una autoritat internacional. Despr��s de la introducci�� de la teoria del r��gim internacional i el concepte de coneixement basats en les comunitats epist��miques, l'article revisa l'estat actual de la governabilitat de l'energia mundia. A continuaci�� es presenta una comparaci�� d'aquesta estructura amb els r��gims de govern nacional i regional, d'una banda, i amb r��gims globals ambientals i de salut, de l'altra

Universality class of fiber bundles with strong heterogeneities

We study the effect of strong heterogeneities on the fracture of disordered materials using a fiber bundle model. The bundle is composed of two subsets of fibers, i.e. a fraction 0 ��� �� ��� 1 of fibers is unbreakable, while the remaining 1 - �� fraction is characterized by a distribution of breaking thresholds. Assuming global load sharing, we show analytically that there exists a critical fraction of the components ��c which separates two qualitatively diferent regimes of the system: below ��c the burst size distribution is a power law with the usual exponent ��= 5/2, while above ��c the exponent switches to a lower value �� = 9/4 and a cutoff function occurs with a diverging characteristic size. Analyzing the macroscopic response of the system we demonstrate that the transition is conditioned to disorder distributions where the constitutive curve has a single maximum and an inflexion point defining a novel universality class of breakdown phenomena

Two complementary molecular energy decomposition schemes: the Mayer and Ziegler-Rauk methods in comparison

In the present paper we discuss and compare two different energy decomposition schemes: Mayer's Hartree-Fock energy decomposition into diatomic and monoatomic contributions [Chem. Phys. Lett. 382, 265 (2003)], and the Ziegler-Rauk dissociation energy decomposition [Inorg. Chem. 18, 1558 (1979)]. The Ziegler-Rauk scheme is based on a separation of a molecule into fragments, while Mayer's scheme can be used in the cases where a fragmentation of the system in clearly separable parts is not possible. In the Mayer scheme, the density of a free atom is deformed to give the one-atom Mulliken density that subsequently interacts to give rise to the diatomic interaction energy. We give a detailed analysis of the diatomic energy contributions in the Mayer scheme and a close look onto the one-atom Mulliken densities. The Mulliken density ��A has a single large maximum around the nuclear position of the atom A, but exhibits slightly negative values in the vicinity of neighboring atoms. The main connecting point between both analysis schemes is the electrostatic energy. Both decomposition schemes utilize the same electrostatic energy expression, but differ in how fragment densities are defined. In the Mayer scheme, the electrostatic component originates from the interaction of the Mulliken densities, while in the Ziegler-Rauk scheme, the undisturbed fragment densities interact. The values of the electrostatic energy resulting from the two schemes differ significantly but typically have the same order of magnitude. Both methods are useful and complementary since Mayer's decomposition focuses on the energy of the finally formed molecule, whereas the Ziegler-Rauk scheme describes the bond formation starting from undeformed fragment densities

Systematic study of the static electrical properties of the CO molecule: influence of the basis set size and correlation energy

The influence of the basis set size and the correlation energy in the static electrical properties of the CO molecule is assessed. In particular, we have studied both the nuclear relaxation and the vibrational contributions to the static molecular electrical properties, the vibrational Stark effect (VSE) and the vibrational intensity effect (VIE). From a mathematical point of view, when a static and uniform electric field is applied to a molecule, the energy of this system can be expressed in terms of a double power series with respect to the bond length and to the field strength. From the power series expansion of the potential energy, field-dependent expressions for the equilibrium geometry, for the potential energy and for the force constant are obtained. The nuclear relaxation and vibrational contributions to the molecular electrical properties are analyzed in terms of the derivatives of the electronic molecular properties. In general, the results presented show that accurate inclusion of the correlation energy and large basis sets are needed to calculate the molecular electrical properties and their derivatives with respect to either nuclear displacements or/and field strength. With respect to experimental data, the calculated power series coefficients are overestimated by the SCF, CISD, and QCISD methods. On the contrary, perturbation methods (MP2 and MP4) tend to underestimate them. In average and using the 6-311 + G(3df) basis set and for the CO molecule, the nuclear relaxation and the vibrational contributions to the molecular electrical properties amount to 11.7%, 3.3%, and 69.7% of the purely electronic ��, ��, and �� values, respectively

Iowa Power Fund Board Project Report Update, July 29, 2009

Climate refers to the long-term course or condition of weather, usually over a time scale of decades and longer. It has been documented that our global climate is changing (IPCC 2007, Copenhagen Diagnosis 2009), and Iowa is no exception. In Iowa, statistically significant changes in our precipitation, streamflow, nighttime minimum temperatures, winter average temperatures, and dewpoint humidity readings have occurred during the past few decades. Iowans are already living with warmer winters, longer growing seasons, warmer nights, higher dew-point temperatures, increased humidity, greater annual streamflows, and more frequent severe precipitation events (Fig. 1-1) than were prevalent during the past 50 years. Some of the impacts of these changes could be construed as positive, and some are negative, particularly the tendency for greater precipitation events and flooding. In the near-term, we may expect these trends to continue as long as climate change is prolonged and exacerbated by increasing greenhouse gas emissions globally from the use of fossil fuels and fertilizers, the clearing of land, and agricultural and industrial emissions. This report documents the impacts of changing climate on Iowa during the past 50 years. It seeks to answer the question, ���What are the impacts of climate change in Iowa that have been observed already?��� And, ���What are the effects on public health, our flora and fauna, agriculture, and the general economy of Iowa?���

Iowa Office of Energy Independence Iowa Power Fund Summary of Economic Impact Study, December 16, 2010

A newly completed study commissioned by the Iowa Office of Energy Independence shows increased jobs, tax revenue and economic activity as a result of Iowa Power Fund projects. The analysis is divided into two parts. Part I assesses the specific impacts of projects that have been funded directly. Part II offers an analysis of the long term impacts when projects are successfully replicated.

Thermostatistical description of small systems in nonequilibrium conditions: Energy conversion and harvesting

Hysteresis cycles are very important features of energy conversion and harvesting devices, such as batteries. The ef���ciency of these may be strongly affected by the physical size of the system. Here, we show that in systems which are small enough, the existence of physical boundaries which produce nonhomogeneities of the interaction potential gives rise to in���ections and barriers in the associated free energy. This in turn brings on irreversible processes which can be triggered under suitable external conditions imposed by a heat bath. As an example, by controlling the temperature, the state of a small system may be impelled to oscillate between two different structural con���gurations or aggregation states avoiding equilibrium coexistence and therefore dissipating energy. This cyclical behavior associated with a hysteresis cycle may be prototypical of energy conversion, storage, or generating nanodevices, as exempli���ed by Li-ion insertion batteries.

On an asymptotic formula for the maximum voltage drop in a on-chip power distribution network

We present a new asymptotic formula for the maximum static voltage in a simplified model for on-chip power distribution networks of array bonded integrated circuits. In this model the voltage is the solution of a Poisson equation in an infinite planar domain whose boundary is an array of circular pads of radius ", and we deal with the singular limit �� ��� 0 case. In comparison with approximations that appear in the electronic engineering literature, our formula is more complete since we have obtained terms up to order ��15. A procedure will be presented to compute all the successive terms, which can be interpreted as using multipole solutions of equations involving spatial derivatives of functions. To deduce the formula we use the method of matched asymptotic expansions. Our results are completely analytical and we make an extensive use of special functions and of the Gauss constant G

City Energy Management Program A Regional Energy Manager Approach, May 2014

Through the City Energy Management Program, energy managers will directly work with up to 20 municipalities in Iowa to help identify opportunities to reduce energy costs in city-owned buildings, exterior lighting, and water/wastewater facilities. This assistance will be provided to the selected municipalities who will provide an in-kind match to achieve energy efficiency within their community. Power Point of theses resources.

Report on theorerical results of power generation and conversion

Experimental results of a new controller able to support bidirectional power flow in a full-bridge rectifier with boost-like topology are obtained. The controller is computed using port Hamiltonian passivity techniques for a suitable generalized state space averaging truncation system, which transforms the control objectives, namely constant output voltage dc-bus and unity input power factor, into a regulation problem. Simulation results for the full system show the essential correctness of the simplifications introduced to obtain the controller, although some small experimental discrepancies point to several aspects that need further improvement.