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Two key challenges in optimal control include efficiently solving high-dimensional problems and handling optimal control problems with state-dependent running costs. In this paper, we consider a class of optimal control problems whose running costs consist of a quadratic on the control variable and a convex, non-negative, piecewise affine function on the state variable. We provide the analytical solution for this class of optimal control problems as well as a Hopf-type representation formula for the corresponding Hamilton-Jacobi partial differential equations. Finally, we propose efficient numerical algorithms based on our Hopf-type representation formula, convex optimization algorithms, and min-plus techniques. We present several high-dimensional numerical examples, which demonstrate that our algorithms overcome the curse of dimensionality. We also describe a field-programmable gate array (FPGA) implementation of our numerical solver whose latency scales linearly in the spatial dimension and that achieves approximately a 40 times speedup compared to a parallelized central processing unit (CPU) implementation. Thus, our numerical results demonstrate the promising performance boosts that FPGAs are able to achieve over CPUs. As such, our proposed methods have the potential to serve as a building block for solving more complicated high-dimensional optimal control problems in real-time. [ABSTRACT FROM AUTHOR]

We propose a class of novel fractional-order optimization algorithms. We define a fractional-order gradient via the Caputo fractional derivatives that generalizes integer-order gradient. We refer it to as the Caputo fractional-based gradient, and develop an efficient implementation to compute it. A general class of fractional-order optimization methods is then obtained by replacing integer-order gradients with the Caputo fractional-based gradients. To give concrete algorithms, we consider gradient descent (GD) and Adam, and extend them to the Caputo fractional GD (CfGD) and the Caputo fractional Adam (CfAdam). We demonstrate the superiority of CfGD and CfAdam on several large scale optimization problems that arise from scientific machine learning applications, such as ill-conditioned least squares problem on real-world data and the training of neural networks involving non-convex objective functions. Numerical examples show that both CfGD and CfAdam result in acceleration over GD and Adam, respectively. We also derive error bounds of CfGD for quadratic functions, which further indicate that CfGD could mitigate the dependence on the condition number in the rate of convergence and results in significant acceleration over GD. [ABSTRACT FROM AUTHOR]

Abstract: Brain-derived neurotrophic factor (BDNF) is involved in the differentiation and the survival of neurons. It has also been shown to be associated with the regrowth of neurons of damaged spinal cord and the modulation of ionic currents by acting on sodium channels and NMDA receptors through tyrosine kinase B (TrkB) receptors. We investigated the effects of BDNF on rhythm generation induced by disinhibition in dissociated cultures from embryonic rat spinal cord (E14), with extracellular multisite recordings (MultiElectrode Arrays, MEAs) or intracellular patch-clamp recordings. Exogenous BDNF had only minor effects on the bursting by increasing the activity during the burst. This increase of activity is suggested to be mediated by a potentiation of the postsynaptic NMDA receptors because it has been found that BDNF potentiates the NMDA-evoked depolarization in cultures incubated with BDNF for 10min. Possible direct effects of BDNF on sodium channels were also investigated by local application of BDNF to the soma of patched neurons but no depolarization was observed. Long-term application of BDNF strongly decreased the activity during the burst and also the number of active electrodes, possibly due to a decrease in network density. [Copyright &y& Elsevier]

Kawasaki disease (KD) is an acute vasculitis with a particular tropism for the coronary arteries. KD mainly affects male children between 6 months and 5 years of age. The diagnosis is clinical, based on the international American Heart Association criteria. It should be systematically considered in children with a fever, either of 5 days or more, or of 3 days if all other criteria are present. It is important to note that most children present with marked irritability and may have digestive signs. Although the biological inflammatory response is not specific, it is of great value for the diagnosis. Because of the difficulty of recognising incomplete or atypical forms of KD, and the need for urgent treatment, the child should be referred to a paediatric hospital as soon as the diagnosis is suspected. In the event of signs of heart failure (pallor, tachycardia, polypnea, sweating, hepatomegaly, unstable blood pressure), medical transfer to an intensive care unit (ICU) is essential. The standard treatment is an infusion of IVIG combined with aspirin (before 10 days of fever, and for a minimum of 6 weeks), which reduces the risk of coronary aneurysms. In case of coronary involvement, antiplatelet therapy can be maintained for life. In case of a giant aneurysm, anticoagulant treatment is added to the antiplatelet agent. The prognosis of KD is generally good and most children recover without sequelae. The prognosis in children with initial coronary involvement depends on the progression of the cardiac anomalies, which are monitored during careful specialised cardiological follow-up. [ABSTRACT FROM AUTHOR]

• Developing countries' (DCs') people who are neither poor nor rich are increasingly categorized as the "middle class". • The heterogeneous socio-economic characteristics and subjective preferences of this group are mapped over four countries. • DCs' middle-classes share strong and identifying commonalities as to consumption, investment and preference for stability. • They also present strong specificities across subgroups that might preclude class identification and stabilization. • Knowing better this vulnerable group is urgent to target policies and investment on their socio-economic consolidation. The term "middle class" is increasingly used to qualify the mass of people in developing countries who are neither poor nor rich and share consumption patterns historically associated with the western middle class. However, what differentiates them from the ideal-typical middle class, as well as the extent to which emerging middle classes differ across developing countries, has only been marginally documented by economists to date. This article proposes to scratch beneath the surface of the so-called middle-class that is burgeoning in developing countries by documenting the commonalities and differences hidden by the all-encompassing term of "middle class" for a set of developing countries exhibiting different levels of income, economic structures and socio-political systems: Brazil, Côte d'Ivoire, Turkey and Vietnam. Relying on quantitative and qualitative micro-economic data, our paper compares the objective characteristics (occupation, education, income), behavior and subjective expectations of the people standing in the middle of the income distribution in the four countries. Four main research questions structure the paper. Where is the middle? How is the middle specific? Who is in the middle? What does the middle aspire to? Results show that the middle-income group in each country covers distinct realities. Although some similar characteristics and behaviors are observable, our results reveal a strong heterogeneity within each national middle class, with no fewer than four to seven socio-economic subgroups, and strong country-specific traits as most of the subgroups are deeply rooted in the country's specific historical trajectory. In each country, our analysis also unveils a pattern of bipolarization between a rather affluent and stable middle class and a "new" or more vulnerable one. Finally, middle class members appear to be characterized by an individualist positioning and the absence of a marked political commitment, challenging the common assumption that developing countries' middle classes are agents of political change. [ABSTRACT FROM AUTHOR]

Résumé La catastrophe de type attentat constitue un événement qui, par son intentionnalité humaine, sa forte valence médiatique, symbolique et sociétale, revêt un fort potentiel traumatogène. Depuis quelques années déjà, les Cellules d’Urgence Médico-Psychologiques interviennent en immédiat sur ces événements. Leur action « sur le terrain », par exemple lors de l’attentat perpétré à Saint-Quentin-Fallavier, petite commune située entre l’Isère et le Rhône, le 26 juin 2015, mérite d’être mieux comprise. Outre le repérage de l’état clinique par le tri et les soins directs prodigués aux victimes impliquées, l’organisation et la gestion psychologique de la crise générée par un tel événement constituent des stratégies thérapeutiques indirectes tout à fait essentielles et spécifiques. Disaster such as terrorist attack is a human design event that has a strong mediatic, symbolic and social impact and therefore is a high potentially traumatic event. For several years now, medico-psychological units have been providing immediate cares on that kind of event. Their action “on the field”, for example on Saint-Quentin-Fallavier terrorist attack, a little municipality between the Rhône and the Isère area, the 26th of June 2015, has to be better understood. Furthermore the screening of clinical state and direct cares provided to the victims involved in such event, organization and crisis intervention are indirect but part of health care strategies; they are specific and essential. [ABSTRACT FROM AUTHOR]

Nociceptive processing is tuned by GABAA receptor-mediated inhibition in the spinal cord dorsal horn that undergoes postnatal maturation in rodents. These GABAergic inhibitory postsynaptic currents (IPSCs) are modulated by 3α5α-reduced steroids during early postnatal development in spinal cord lamina II. Thus an enhanced phasic inhibition is present in neonates and decreases over time. GABA can also activate extrasynaptic receptors, giving rise to tonic inhibition. In this study, we characterized the contribution of plasma corticosterone (CORT) to postnatal maturation of spinal phasic and, for the first time, tonic GABAergic inhibitions. We used Fisher and Lewis rat strains displaying respectively high and low hypothalamic-pituitary-adrenal axis reactivity, compared to control Sprague-Dawley rats. Measured plasma CORT levels were significantly higher in Fisher rats, which also displayed significantly higher mechanical nociceptive thresholds, supporting the hypothesis of an antinociceptive action of CORT. Recorded GABAA IPSCs shortened during maturation in all strains while remaining larger in Fisher rats. Blocking the 5α-reduction of steroids in Fisher rats produced a further decrease of IPSC deactivation time constant. In contrast, GABAA tonic inhibition progressively increased during maturation, without any difference among strains. In conclusion, we show that both phasic and tonic GABAergic inhibitions undergo postnatal maturation in lamina II. Moreover spinal production of 3α5α-reduced steroids that presumably derive from plasma CORT is correlated to spinal GABAA phasic (but not tonic) inhibition and to mechanical nociceptive thresholds. [ABSTRACT FROM AUTHOR]

Abstract: To the aim of development of a spatially resolved x-ray imaging system intended for Inertial Confinement Fusion (ICF) experiments at the Laser Méga Joule (LMJ) facility, new plastic scintillators have been designed. The main characteristics are the following: fast decay time, red emission and good x-rays photoelectric absorption in the range 10–40keV. These scintillators are synthesized by copolymerization of different monomers with an organometallic compound. In this matrix two fluorescent compounds are embedded, allowing to shift the energy from the UV to the near IR spectrum. Several parameters were studied: fluorophores concentration, nature of the secondary fluorophore and lead concentration. An outstanding effective atomic number of 53 has been reached, for a loading of lead corresponding to 29wt%. Thus, small cylinders were prepared and their performances under x-ray beam studied and compared with those of inorganic Cerium-doped Yttrium Aluminum Garnet reference scintillator (Y3Al5O12:Ce3+). Eventually, such new scintillators or their next generation could replace expensive and brittle inorganic scintillators, inducing a strong industrial potential. [Copyright &y& Elsevier]

The Henipavirus genome is encapsidated by the nucleoprotein (N) within a helical nucleocapsid that recruits the polymerase complex via the phosphoprotein (P). In a previous study, we reported that in henipaviruses, the N-terminal domain of the phosphoprotein and the C-terminal domain of the nucleoprotein (TAIL) are both intrinsically disordered. Here we show that Henipavirus TAIL domains are also disordered in the context of full-length nucleoproteins. We also report the cloning, purification, and characterization of the C-terminal X domains (PXD) of Henipavirus phosphoproteins. Using isothermal titration calorimetry, we show that N TAIL and P~ form a 1:1 stoichiometric complex that is stable under NaCI concentrations as high as 1 M and has a KD in the μM range. Using far-UV circular dichroism and nuclear magnetic resonance, we show that PXD triggers an increase in the a-helical content of TAIL, Using fluorescence spectroscopy, we show that Pxi has no impact on the chemical environment of a Trp residue introduced at position 527 of the Henipavirus TAIL domain, thus arguing for the lack of stable contacts between the C termini of TAIL and PXD Finally, we present a tentative structural model of the TAIL-PXD interaction in which a short, order-prone region of TAIL (α-MoRE; amino acids 473493) adopts an a-helical conformation and is embedded between helices a2 and α3 of αXD)' leading to a relatively small interface dominated by hydrophobic contacts. The present results provide the first detailed experimental characterization of the N-P interaction in henipaviruses and designate the NTAIL-PXD interaction as a valuable target for rational antiviral approaches. [ABSTRACT FROM AUTHOR]

Maurocalcine is a 33-mer peptide initially isolated from the venom of a Tunisian scorpion. It has proved itself valuable as a pharmacological activator of the ryanodine receptor and has helped the understanding of the molecular basis underlying excitation-contraction coupling in skeletal muscles. Because of its positively charged nature, it is also an innovative vector for the cell penetration of various compounds. We report a novel maurocalcine analog with improved properties: (i) the complete loss of pharmacological activity, (ii) preservation of the potent ability to carry cargo molecules into cells, and (iii) coupling chemistries not affected by the presence of internal cysteine residues of maurocalcine. We did this by replacing the six internal cysteine residues of maurocalcine by isosteric 2-aminobutyric acid residues and by adding an additional N-terminal biotinylated lysine (for a proof of concept analog) or an N-terminal cysteine residue (for a chemically competent coupling analogue). Additional replacement of a glutamate residue by alanyl at position 12 further improves the potency of these analogues. Coupling to several cargo molecules or nanoparticles are presented to illustrate the cell penetration potency and usefulness of these pharmacologically inactive analogs. [ABSTRACT FROM AUTHOR]

Chk2 is a key player of the DNA damage signalling pathway. To identify new regulators of this kinase, we performed a yeast two-hybrid screen and found that Chk2 associated with the B′ regulatory subunit of protein phosphatase PP2A. In vitro GST-Chk2 pulldowns demonstrated that B′γ isoforms bound to Chk2 with the strongest apparent affinity. This was confirmed in cellulo by co-immunoprecipitation after overexpression of the respective partners in HEK293 cells. The A and C subunits of PP2A were present in the complexes, suggesting that Chk2 was associated with a functionnal PP2A. In vitro kinase assays showed that B′γ3 was a potent Chk2 substrate. This phosphorylation increased the catalytic phosphatase activity of PP2A measured on MAP kinase-phosphorylated myelin basic protein as well as on autophosphorylated Chk2. Finally, we demonstrated that overexpressing B′γ3 in HEK293 suppressed the phosphorylation of Chk2 induced by a genotoxic treatment, suggesting that PP2A may counteract the action of the checkpoint kinase in living cells. [Copyright &y& Elsevier]

Maurotoxin (MTX) is a 34-residue toxin that has been isolated initially from the venom of the scorpion Scorpio maurus palmatus. It presents a large number of pharmacological targets, including small conductance Ca[sup 2+]activated and voltage-gated K[sup +] channels. Contrary to other toxins of the α-KTx6 family (Pi1, Pi4, Pi7, and HsTx1), MTX exhibits a unique disulfide bridge organization of the type C1-C5, C2-C6, C3-C4, and C7-C8 (instead of the conventional C1-C5, C2-C6, C3-C7, and C4C8, herein referred to as Pi1-like) that does not prevent its folding along the classic α/β scaffold of scorpion toxins. Here, we developed an innovative strategy of chemical peptide synthesis to produce an MTX variant (MTX[sub Pi1]) with a conventional pattern of disulfide bridging without any alteration of the toxin chemical structure. This strategy was used solely to address the impact of half-cystine pairings on MTX structural properties and pharmacology. The data indicate that MTX[sub Pi1] displays some marked changes in affinities toward the target K[sup +] channels. Computed docking analyses using molecular models of both MTX[sub Pi1] and the various voltage-gated K[sup +] channel subtypes (Shaker B, K[sub v]1.2, and I[sub v]1.3) were found to correlate with MTX[sub Pi1] pharmacology. A functional map detailing the interaction between MTX[sub Pi1] and Shaker B channel was generated in line with docking experiments. [ABSTRACT FROM AUTHOR]

Discusses a study suggesting that the C-terminal domain of the measles virus nucleoprotein is intrinsically disordered and folds upon binding to the C-terminal moiety of the phosphoprotein. Bacterial expression of the virus; Purification and characterization; Sequence, spectroscopic and hydrodynamic properties.