Proteasome inhibitor (MG132) rescues Nav1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx (5cv) mice

The cardiac voltage-gated sodium channel, Nav1.5, plays a central role in cardiac excitability and impulse propagation and associates with the dystrophin multiprotein complex at the lateral membrane of cardiomyocytes. It was previously shown that Nav1.5 protein content and the sodium current (l Na) were both decreased in cardiomyocytes of dystrophin-deficient mdx (5cv) mice. In this study, wild-type and mdx (5cv) mice were treated for 7 days with the proteasome inhibitor MG132 (10 μg/Kg/24 h) using implanted osmotic mini pumps. MG132 rescued both the total amount of Nav1.5 protein and l Na but, unlike in previous studies, de novo expression of dystrophin was not observed in skeletal or cardiac muscle. This study suggests that the reduced expression of Nav1.5 in dystrophin-deficient cells is dependent on proteasomal degradation.

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1.

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have shown that transgenic mice expressing R192Q or S218L FHM1 mutations have increased SD frequency and propagation speed; enhanced corticostriatal propagation; and, similar to the human FHM1 phenotype, more severe and prolonged post-SD neurological deficits. The susceptibility to SD and neurological deficits is affected by allele dosage and is higher in S218L than R192Q mutants. Further, female S218L and R192Q mutant mice were more susceptible to SD and neurological deficits than males. This sex difference was abrogated by ovariectomy and senescence and was partially restored by estrogen replacement, implicating ovarian hormones in the observed sex differences in humans with FHM1. These findings demonstrate that genetic and hormonal factors modulate susceptibility to SD and neurological deficits in FHM1 mutant mice, providing a potential mechanism for the phenotypic diversity of human migraine and aura.

Monte Carlo modeling of polarized light propagation: Stokes vs Jones - Part I

This bipartite comparative study aims at inspecting the similarities and differences between the Jones and Stokes–Mueller formalisms when modeling polarized light propagation with numerical simulations of the Monte Carlo type. In this first part, we review the theoretical concepts that concern light propagation and detection with both pure and partially/totally unpolarized states. The latter case involving fluctuations, or “depolarizing effects,” is of special interest here: Jones and Stokes–Mueller are equally apt to model such effects and are expected to yield identical results. In a second, ensuing paper, empirical evidence is provided by means of numerical experiments, using both formalisms.

Mass Movement-Induced Tsunami Hazard on Perialpine Lake Lucerne (Switzerland): Scenarios and Numerical Experiments

Previous studies of the sediments of Lake Lucerne have shown that massive subaqueous mass movements affecting unconsolidated sediments on lateral slopes are a common process in this lake, and, in view of historical reports describing damaging waves on the lake, it was suggested that tsunamis generated by mass movements represent a considerable natural hazard on the lakeshores. Newly performed numerical simulations combining two-dimensional, depth-averaged models for mass-movement propagation and for tsunami generation, propagation and inunda- tion reproduce a number of reported tsunami effects. Four analysed mass-movement scenarios—three based on documented slope failures involving volumes of 5.5 to 20.8 9 106 m3—show peak wave heights of several metres and maximum runup of 6 to [10 m in the directly affected basins, while effects in neighbouring basins are less drastic. The tsunamis cause large-scale inundation over distances of several hundred metres on flat alluvial plains close to the mass-movement source areas. Basins at the ends of the lake experience regular water-level oscillations with characteristic periods of several minutes. The vulnerability of potentially affected areas has increased dramatically since the times of the damaging historical events, recommending a thorough evaluation of the hazard.

Auxin Regulates the Initiation and Radial Position of Plant Lateral Organs

Leaves originate from the shoot apical meristem, a small mound of undifferentiated tissue at the tip of the stem. Leaf formation begins with the selection of a group of founder cells in the so-called peripheral zone at the flank of the meristem, followed by the initiation of local growth and finally morphogenesis of the resulting bulge into a differentiated leaf. Whereas the mechanisms controlling the switch between meristem propagation and leaf initiation are being identified by genetic and molecular analyses, the radial positioning of leaves, known as phyllotaxis, remains poorly understood. Hormones, especially auxin and gibberellin, are known to influence phyllotaxis, but their specific role in the determination of organ position is not clear. We show that inhibition of polar auxin transport blocks leaf formation at the vegetative tomato meristem, resulting in pinlike naked stems with an intact meristem at the tip. Microapplication of the natural auxin indole-3-acetic acid (IAA) to the apex of such pins restores leaf formation. Similarly, exogenous IAA induces flower formation on Arabidopsis pin-formed1-1 inflorescence apices, which are blocked in flower formation because of a mutation in a putative auxin transport protein. Our results show that auxin is required for and sufficient to induce organogenesis both in the vegetative tomato meristem and in the Arabidopsis inflorescence meristem. In this study, organogenesis always strictly coincided with the site of IAA application in the radial dimension, whereas in the apical–basal dimension, organ formation always occurred at a fixed distance from the summit of the meristem. We propose that auxin determines the radial position and the size of lateral organs but not the apical–basal position or the identity of the induced structures.

Fine-grained indoor positioning and tracking systems

Indoor positioning has attracted considerable attention for decades due to the increasing demands for location based services. In the past years, although numerous methods have been proposed for indoor positioning, it is still challenging to find a convincing solution that combines high positioning accuracy and ease of deployment. Radio-based indoor positioning has emerged as a dominant method due to its ubiquitousness, especially for WiFi. RSSI (Received Signal Strength Indicator) has been investigated in the area of indoor positioning for decades. However, it is prone to multipath propagation and hence fingerprinting has become the most commonly used method for indoor positioning using RSSI. The drawback of fingerprinting is that it requires intensive labour efforts to calibrate the radio map prior to experiments, which makes the deployment of the positioning system very time consuming. Using time information as another way for radio-based indoor positioning is challenged by time synchronization among anchor nodes and timestamp accuracy. Besides radio-based positioning methods, intensive research has been conducted to make use of inertial sensors for indoor tracking due to the fast developments of smartphones. However, these methods are normally prone to accumulative errors and might not be available for some applications, such as passive positioning. This thesis focuses on network-based indoor positioning and tracking systems, mainly for passive positioning, which does not require the participation of targets in the positioning process. To achieve high positioning accuracy, we work on some information of radio signals from physical-layer processing, such as timestamps and channel information. The contributions in this thesis can be divided into two parts: time-based positioning and channel information based positioning. First, for time-based indoor positioning (especially for narrow-band signals), we address challenges for compensating synchronization offsets among anchor nodes, designing timestamps with high resolution, and developing accurate positioning methods. Second, we work on range-based positioning methods with channel information to passively locate and track WiFi targets. Targeting less efforts for deployment, we work on range-based methods, which require much less calibration efforts than fingerprinting. By designing some novel enhanced methods for both ranging and positioning (including trilateration for stationary targets and particle filter for mobile targets), we are able to locate WiFi targets with high accuracy solely relying on radio signals and our proposed enhanced particle filter significantly outperforms the other commonly used range-based positioning algorithms, e.g., a traditional particle filter, extended Kalman filter and trilateration algorithms. In addition to using radio signals for passive positioning, we propose a second enhanced particle filter for active positioning to fuse inertial sensor and channel information to track indoor targets, which achieves higher tracking accuracy than tracking methods solely relying on either radio signals or inertial sensors.

A generic framework for the analysis and specialization of kogic programs

The relationship between abstract interpretation [2] and partial evaluation [5] has received considerable attention and (partial) integrations have been proposed starting from both the partial deduction (see e.g. [6] and its references) and abstract interpretation perspectives. Abstract interpretation-based analyzers (such as the CiaoPP analyzer [9,4]) generally compute a program analysis graph [1] in order to propagate (abstract) call and success information by performing fixpoint computations when needed. On the other hand, partial deduction methods [7] incorporate powerful techniques for on-line specialization including (concrete) call propagation and unfolding.

Five-year results of a slant-path propagation experiment at 20 GHz in Madrid

Satellite operators are starting to use the Ka-band (30/20 GHz) for communications systems requiring higher traffic capacity. The use of this band is expected to experience a significant growth in the next few years, as several operators have reported plans to launch new satellites with Ka-band capacity. It is worth mentioning the Ka-Sat satellite in Europe, launched in 2010, and ViaSat-1, of 2011, with coverage of USA1. Some other examples can be found in other parts of the World. Recent satellite communications standards, such as DVB-S22 or DVB-RCS3, which provide means to mitigate propagation impairments, have been developed with the objective of improving the use of the Ka-band, in comparison with previous technical standards. In the next years, the ALPHASAT satellite will bring about new opportunities4 for carrying out propagation and telecommunication experiments in the Ka- and Q/V-bands. Commercial uses are focused on the provision of high speed data communications, for Internet access and other applications. In the near future, it is expected that higher and higher data rates will also be needed to broadcast richer multimedia contents, including HD-TV, interactive content or 3D-TV. All of these services may be provided in the future by satellites of the current generation, whose life span can extend up to 2025 in some cases. Depending on local regulations, the available bandwidth for the satellite fixed and broadcasting services in the Ka-band is in excess of several hundred MHz, bidirectional, comprising more than 1 GHz for each sub-band in some cases. In this paper, the results of a propagation experiment that is being carried out at Universidad Politécnica de Madrid (UPM), Spain, are presented5. The objective of the experiment is twofold: gathering experimental time series of attenuation and analyzing them in order to characterize the propagation channel at these frequencies6. The experiment and statistical results correspond to five complete years of measurements. The experiment is described in more detail in Section II. Yearly characteristics of rain attenuation are presented in Section III, whereas Section IV is dedicated to the monthly, seasonal, and hourly characteristics. Section V covers the dynamic characteristics of this propagation effect, just before the conclusions are described in Section VI.

Neurite, a finite difference large scale parallel program for the simulation of the electrical signal propagation in neurites under mechanical loading

With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, function of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells has only very recently been proposed (Jerusalem et al., 2013). In this paper, we present the implementation details of Neurite: the finite difference parallel program used in this reference. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite-explicit and implicit-were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between lectrophysiology and mechanics (Jerusalem et al., 2013). This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon, a segmented dendritic tree, and a damaged axon. The capabilities of the program to deal with large scale scenarios, segmented neuronal structures, and functional deficits under mechanical loading are specifically highlighted.

Improved walnut mass micropropagation through the combined use of phloroglucinol and FeEDDHA

Despite the socioeconomic importance of walnut trees, poor rooting and recalcitrance to in vitro culture have hampered the establishment of high-yield clonal plantations. To improve walnut micropropagation, we introduced several modifications to current methods and evaluated the effects on microshoot performance and acclimatization. Nine selected genotypes (13-year-old trees) of the commercial hybrid Juglans major 209 x J. regia were cultured in vitro on DKW-C medium supplemented with 4.4 µM BA and 50 µM IBA. A protocol was developed that relies on the use of 0.40 mM phloroglucinol during shoot multiplication, 0.20 mM previous root induction, and 6.81 mg/L Fe3+ (FeEDDHA). Moreover, the addition of 83.2 µM glucose during the root expression phase significantly improved plant survival during acclimatization. Phloroglucinol promoted microshoot elongation but inhibited rooting, especially at concentrations above 0.40 mM. Replacing FeEDTA by FeEDDHA diminished chlorotic symptoms and improved rooting, with up to 90% microshoots developing viable roots. Likewise, glucose was more efficient than sucrose or fructose in promoting plant survival. At the proposed working concentrations, neither glucose nor FeEDDHA caused any noticeable deleterious effect on walnut micropropagation. Microscopic analysis revealed the physical continuity between adventitious roots and stem pericycles. Analysis of leaf genomic DNA with eight polymorphic microsatellite markers was supportive of the clonal fidelity and genetic stability of the micropropagated material. Successful clonal plantations (over 5,800 ramets) have been established by applying this protocol.

Regulation of cell signaling by the cytoplasmic domains of the heat-stable enterotoxin receptor: identification of autoinhibitory and activating motifs.

Infection with enterotoxigenic Escherichia coli is a leading cause of traveler's diarrhea. Many enterotoxigenic E. coli strains produce heat-stable enterotoxin (ST), a peptide that binds to the intestinal receptor guanylyl cyclase C known as STaR. The toxin-receptor interaction elevates intracellular cGMP, which then activates apical chloride secretion, resulting in secretory diarrhea. In this report, we examine how the intracellular domains of STaR participate in the propagation and regulation of signaling. We show that STaR exists as an oligomer in both the presence and the absence of toxin. We also demonstrate that deletion of the intracellular kinase-homology domain produces a constitutively active mutant, suggesting that this domain subserves an autoinhibitory function. Finally, we constructed a point mutant within a highly conserved region of the cyclase domain that completely inactivates the catalytic activity of guanylyl cyclase. Cotransfection of this point mutant with wild-type receptor causes a dominant-negative effect on receptor activation. This suggests that interaction of receptor subunits is required for toxin-induced activation and that the cyclase domain is involved in this essential interaction. We propose that the binding of ST to STaR promotes a conformational change across the cell membrane. This removes the inhibitory effects of the kinase-homology domain and promotes an interaction between cyclase domains that leads to receptor activation. The data suggest a paradigm of signal transduction that may also be relevant to other members of the guanylyl cyclase receptor family.

Temperature influence on the physical and mechanical properties of a porous rock: San Julian's calcarenite

This work discusses the results from tests which were performed in order to study the effect of high temperatures in the physical and mechanical properties of a calcarenite (San Julian's stone). Samples, previously heated at different temperatures (from 105 °C to 600 °C), were tested. Non-destructive tests (porosity and ultrasonic wave propagation) and destructive tests (uniaxial compressive strength and slake durability test) were performed over available samples. Furthermore, the tests were carried out under different conditions (i.e. air-cooled and water-cooled) in order to study the effect of the fire off method. The results show that uniaxial compressive strength and elastic parameters (i.e. elastic modulus and Poisson's ratio), decrease as the temperature increases for the tested range of temperatures. A reduction of the uniaxial compressive strength up to 35% and 50% is observed in air-cooled and water-cooled samples respectively when the samples are heated to 600 °C. Regarding the Young's modulus, a fall over 75% and 78% in air-cooled and water-cooled samples respectively is observed. Poisson's ratio also declines up to 44% and 68% with the temperature in air-cooled and water-cooled samples respectively. Slake durability index also exhibits a reduction with temperature. Other physical properties, closely related with the mechanical properties of the stone, are porosity, attenuation and propagation velocity of ultrasonic waves in the material. All exhibit considerable changes with temperature.

Statistical digest - U.S. Fish and Wildlife Service.

Title varies slightly.

Belief propagation vs. TAP for decoding corrupted messages

We employ two different methods, based on belief propagation and TAP,for decoding corrupted messages encoded by employing Sourlas's method, where the code word comprises products of K bits selected randomly from the original message. We show that the equations obtained by the two approaches are similar and provide the same solution as the one obtained by the replica approach in some cases K=2. However, we also show that for K>=3 and unbiased messages the iterative solution is sensitive to the initial conditions and is likely to provide erroneous solutions; and that it is generally beneficial to use Nishimori's temperature, especially in the case of biased messages.

Coloring random graphs and maximizing local diversity

We study a variation of the graph coloring problem on random graphs of finite average connectivity. Given the number of colors, we aim to maximize the number of different colors at neighboring vertices (i.e. one edge distance) of any vertex. Two efficient algorithms, belief propagation and Walksat are adapted to carry out this task. We present experimental results based on two types of random graphs for different system sizes and identify the critical value of the connectivity for the algorithms to find a perfect solution. The problem and the suggested algorithms have practical relevance since various applications, such as distributed storage, can be mapped onto this problem.