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Hedgehog pathway inhibitors (HPI) inactivating SMO 1, have become first line treatment for patients with locally advanced BCC (laBCC). HPI safety and efficacy have been shown in clinical trials2,3. Nevertheless, common adverse events lead to treatment discontinuation.

In performance prediction of IR sensor systems for missile detection, apart from the sensor specifications, target signatures are essential variables. Very often, for velocities up to Mach 2-2.5, a simple model based on the aerodynamic heating of a perfect gas was used to calculate the temperatures of missile targets. This typically results in an overestimate of the target temperature with correspondingly large infrared signatures and detection ranges. Especially for even higher velocities, this approach is no longer accurate. Alternatives like CFD calculations typically require more complex sets of inputs and significantly more computing power. The MATLAB code Hyperheat was developed to calculate the time-resolved skin temperature of axisymmetric high speed missiles during flight, taking into account the behaviour of non-perfect gas and proper heat transfer to the missile surface. Allowing for variations in parameters like missile shape, altitude, atmospheric profile, angle of attack, flight duration and super-and hypersonic velocities up to Mach 30 enables more accurate calculations of the actual target temperature. The model calculates a map of the skin temperature of the missile, which is updated over the flight time of the missile. The sets of skin temperature maps are calculated within minutes, even for >100 km trajectories, and can be easily converted in thermal infrared signatures for further processing. This paper discusses the approach taken in Hyperheat. Then, the thermal signature of a set of typical missile threats is calculated using both the simple aerodynamic heating model and the Hyperheat code. The respective infrared signatures are compared, as well as the difference in the corresponding calculated detection ranges. © 2017 SPIE. The Society of Photo-Optical Instrumentation Engineers (SPIE)

We report $^{35}$Cl NMR, ESR, $\mu$SR and specific heat measurements on the $S=1/2$ frustrated kagom\'e magnet kapellasite, $\alpha-$Cu$_3$Zn(OH)$_6$Cl$_2$, where a gapless spin liquid phase is stabilized by a set of competing exchange interactions. Our measurements confirm the ferromagnetic character of the nearest-neighbour exchange interaction $J_1$ and give an energy scale for the competing interactions $|J| \sim 10$ K. The study of the temperature-dependent ESR lineshift reveals a moderate symmetric exchange anisotropy term $D$, with $|D/J|\sim 3$%. These findings validate a posteriori the use of the $J_1 - J_2 - J_d$ Heisenberg model to describe the magnetic properties of kapellasite [Bernu et al., Phys. Rev. B 87, 155107 (2013)]. We further confirm that the main deviation from this model is the severe random depletion of the magnetic kagom\'e lattice by 27%, due to Cu/Zn site mixing, and specifically address the effect of this disorder by $^{35}$Cl NMR, performed on an oriented polycrystalline sample. Surprisingly, while being very sensitive to local structural deformations, our NMR measurements demonstrate that the system remains homogeneous with a unique spin susceptibility at high temperature, despite a variety of magnetic environments. Unconventional spin dynamics is further revealed by NMR and $\mu$SR in the low-$T$, correlated, spin liquid regime, where a broad distribution of spin-lattice relaxation times is observed. We ascribe this to the presence of local low-energy modes., Comment: 15 pages, 11 figures. To appear in Phys. Rev. B

Study Objectives: In this work, we studied the behavior of the fractal dimension during each of the neonatal electroencephalogram (EEG) sleep phases and during the awake state, comparing the results with those of the classical spectral parameters and with zero crossing values. Design: Fractal dimension, zero crossing, and spectral parameters of the EEG bands were determined for each 2-second frame of the EEG sleep-time series. Eight channels of each EEG recording were examined. Participants: Twenty healthy full-term newborns (10 boys and 10 girls) with normal psychomotor development evaluated at 24 and 36 months of age, were chosen to participate in this study. Measurements and Results: Fractal analysis showed that where rhythmic and regular activity are present, as during quiet sleep, the fractal dimension is low and rises when bioelectric activity is more variable and complex, reaching its maximum value during wakefulness. The discriminative value of this parameter was similar to ...

The main objective of this work package is to enable assurance in the development of software-based services in order to increase confidence in their security. The core goal is to incept a transverse methodology that enables to manage assurance throughout the software development life cycle (SDLC). Our research is divided into two main sub-domains: early assurance at the level of requirements, architecture and design using techniques such as refinement and model checking and complementary implementation-based assurance techniques such as testing and runtime verification. This deliverable summarizes the results obtained during the first year of the project. We cover most of the tasks and activities of the work package and address the majority of the challenges set out in the preceding deliverable about the state-of-the-art in assurance for services. Building on this state-of-theart, we have obtained a wide range of strong results and we were able to produce a number of highrated publications, most notably in the areas of refinement, model checking, testing and debugging, and runtime verification.

How to design a security engineering process that can cope with the dynamic evolution of Future Internet scenarios and the rigidity of existing system engineering processes? The SecureChange approach is to orchestrate (as opposed to integrate) security and system engineering concerns by two types of relations between engineering processes: (i) vertical relations between successive security-related processes; and (ii) horizontal relations between mainstream system engineering processes and concurrent security-related processes. This approach can be extended to cover the complete system/ software lifecycle, from early security requirement elicitation to runtime configuration and monitoring, via high-level architecting, detailed design, development, integration and design-time testing. In this paper we illustrate the high-level scientific principles of the approach. © 2011 Springer-Verlag.

International audience; The transient response of Ba(Fe1−xCox)2As2, x=0.08 was studied by pump-probe optical reflectivity. After ultrafast photoexcitation, hot electrons were found to relax with two different characteristic times, indicating the presence of two distinct decay channels: a faster one, of less than 1 ps in the considered pump fluence range and a slower one, corresponding to lattice thermalization and lasting ≅6 ps. Our analysis indicates that the fast relaxation should be attributed to preferential scattering of the electrons with only a subset of the lattice-vibration modes with a second moment of the Eliashberg function λ⟨ω^2⟩≅64 meV^2. The simultaneous excitation of a strong fully symmetric A1g optical phonon corroborates this conclusion and makes it possible to deduce the value of λ≅0.12. This small value for the electron-phonon coupling confirms that a phonon-mediated process cannot be the only mechanism leading to the formation of superconducting pairs in this family of pnictides.

For the next generation high thrust engine Aerospace Propulsion Products (APP) and TNO Defence Security and Safety are developing technology for a high-power innovative restartable igniter working on 90% hydrogen peroxide and a liquid or gaseous fuel (ethanol, methane or hydrogen). This development has been done in steps: from a RGHP monopropellant device to a full-scale bi-propellant catalytic igniter with methane that delivers a minimum of 500 kW of thermal power. The latest version of the igniter has an actively cooled tube that delivers a hot core flow and a cooling flow into the engine combustion chamber that combust further outside of the igniter near a stoichiometric mixture ratio. The advantages of this system are the absence of high voltage electronics to start the igniter, which contribute a considerable part of the development costs and possible failure modes of electrically started igniters. The paper describes the functional design of the bi-propellant methane igniter and will present recent test results.

NATO and the US are involved in developing Ballistic missile defense (BMD) capabilities that must provide protection against various threats, which has received global attention. One needs to carefully consider the consequences of employing the defensive missiles. It is assumed that there will be no subsequent ground effects other than debris from the ballistic missile and the interceptor, when a ballistic missile with a high-explosive warhead has been intercepted. The released warfare agent and the missile contained submunitions are the two major contributors to the ground effects after interception. The consequences of intercepting a ballistic missile with a biological or chemical load are complex, which may provide a host of benefits.

CeRhIn5is known to show an unusual transition at a critical pressure of ∼15 kbar. Specific-heat data show a gradual change in the zero-field "magnetic" specific-heat anomaly from one typical of antiferromagnetic (AF) ordering at ambient pressure to one more characteristic of a Kondo singlet ground state at 21 kbar. However, at 15 kbar there is a discontinuous change from an AF ground state to a superconducting ground state, and evidence of a weak thermodynamic first-order transition. Above the critical pressure, the low-energy excitations are characteristic of superconductivity with line nodes in the energy gap, and, at intermediate pressures, of extended gaplessness. © 2003 Elsevier Science B.V. All rights reserved.

There have been anecdotal reports of an association between coeliac disease and epilepsy with cerebral calcifications that resemble those of the Sturge-Weber syndrome. A series of patients who had epilepsy with calcifications, in whom coeliac disease (CD) was incidentally observed, prompted us to study this association. 43 patients (15 male, age range 4·6-30·7 years) were selected from two series. 31 patients with cerebral calcifications of unexplained origin and epilepsy (series A) underwent intestinal biopsy. 12 patients with CD and epilepsy (series B) underwent computed tomography. Antibodies to gluten, folic acid serum concentrations, were measured, and H LA typing was done in most patients. 24 of the series A patients were identified as having CD on the basis of a flat intestinal mucosa (15/22 with a high concentration of serum antigluten), and 5 series B patients showed cerebral calcifications, giving a total of 29 cases with the combination of CD, epilepsy, and cerebral calcifications (CEC). In 27 of these CEC patients, calcifications were located in the parieto-occipital regions. Only 2 of the series A patients had gastrointestinal symptoms at the time of intestinal biopsy; most patients had recurrent diarrhoea, anaemia, and other symptoms suggestive of CD in the first 3 years of life. The epilepsy in CEC patients was poorly responsive to antiepileptic drugs. Gluten-free diet beneficially affected the course of epilepsy only when started soon after epilepsy onset. Cases of "atypical Sturge-Weber syndrome" (characterised by serpiginous cerebral calcifications and epilepsy without facial port-wine naevus) should be reviewed, and CD should be ruled out in all cases of epilepsy and cerebral calcifications of unexplained origin. © 1992.

Cet article présente les résultats d'une étude du système racinaire de Douglas adultes observé in situ sur fosses pédologiques dans 74 peuplements purs des monts du Beaujolais. Ces travaux mettent en évidence le fait que la morphologie du système racinaire du Douglas est adaptée aux contraintes géopédologiques engendrées par les structures du sol et du substratum géologique, ce qui conditionne sa croissance en hauteur. Des analyses multifactorielles (AFC et CAH) menées sur les variables descriptives de la morphologie du système racinaire des 74 arbres dominants étudiés et sur celles décrivant les systèmes géopédologiques ont permis d'établir sept groupes présentant des caractéristiques homogènes. Ces groupes expliquent 52,6 % de la variance de l'indice de fertilité du peuplement. La croissance en hauteur du Douglas est généralement forte dans cette région mais elle est nettement réduite quand le système racinaire subit de fortes contraintes dans les horizons peu profonds. Les meilleures croissances correspondent à des systèmes racinaires profonds et à décroissance régulière. Une régression linéaire multiple (R² = 0,57) a été établie entre l'indice de production du peuplement et les variables racinaires qui influent le plus fortement sur la croissance du Douglas : la profondeur maximale apparente de l'enracinement, la densité maximale de racines dans un même horizon, la surface racinaire correspondant aux racines fines (diamètre < 5 mm). Des analyses complémentaires montrent en effet que la croissance en hauteur des arbres est fortement liée à la surface occupée par les racines les plus fines, de diamètre inférieur à 1 mm, qui assurent l'essentiel de la nutrition minérale et hydrique du Douglas. Ces observations doivent permettre de mieux choisir les stations et les sols les plus favorables à l'implantation de cette essence, et mettent en évidence des risques de mauvaise croissance, de problèmes sanitaires ou d'échec sur certains sols. / Relationships between geopedological systems and rooting system. Influence on height growth for Douglas-fir in the monts du Beaujolais (France). This paper deals with a study of mature Douglas-fir root systems in 74 pure and even-aged forest stands of middle mountain areas (mounts of Beaujolais). Root systems were studied in situ using trenches open in soils at 1 meter distance from the stem of dominant trees. The results stress that geopedological constraints due to substratum and soil structures have a strong influence on root systems morphology, and on height growth of forest stands. Multivariate analysis (CA and HCA) were led on root systems variables and geopedological variables. Seven homogeneous groups were identified. They explain 52,6 % of variance of dominant height. Douglas fir height growth is correct or strong for all stands but distinctly reduced when root system is superficial and jammed in surface soil horizons. Highest growth correspond to deep and regular root system profiles. A multiple linear regression was carried out between dominant height and major root system variables (R² = 0,57 %) : estimated maximal rooting depth, maximal root density per horizon, fine roots surface (diameter < 5 mm). Height growth is strongly correlated (R² = 0,61) to surface of finest roots (diameter < 1 mm) which provide the main part of water and nutrients. These observations aim at choosing better sites and soils for settling Douglas fir, and at stressing risks of failure, pests or diseases.