Solid-State Excitation Laser for Laser-Ultrasonics

The inspection speed of laser-ultrasonics compared with conventional ultrasonic testing is limited by the pulse repetition rate of the excitation laser. The maximum pulse repetition rate reported up to now for CO2-lasers, which are presently used for nearly all systems, is in the range of 400 Hz. In this paper a new approach based on a diode-pumped solid-state laser is discussed, which is currently being developed. This new excitation laser is designed for a repetition rate of 1 kHz and will operate at a mid-IR wavelength of 3.3 m. The higher repeti-tion rate enables a higher inspection speed, whereas the mid-IR wavelength anticipates a better coupling efficiency. The total power for pumping the laser crystals is transported via flexible optical fibres to the compact laser head, thus allowing operation on a robot arm. The laser head consists of a master oscillator feeding several lines of power amplifiers and in-cludes nonlinear optical wavelength conversion by an optical parametric process. It is char-acterized by a modular construction which provides optimal conditions for operation at high average power as well as for easy maintenance. These features will enable building reliable, long-lived, rugged, smart laser ultrasonic systems in futur

Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal αDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When αDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4-48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of αDEC-205:OVA to DCs in the steady state initially induced 4-7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund\u27s adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with αDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic αCD40 antibody produced large amounts of interleukin 2 and interferon γ, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation

Phosphor im Grünland – Antrieb der Leguminosen, aber Bremse der Phytodiversität?

In our study we investigated the effect of soil phosphorus (P) status on legume occurrence and on phytodiversity of organically managed permanent grassland sites. Therefore, we realized screenings on 2 m x 2 m plots with a clear spatial differentiation between the functional groups ‘legumes’ and ‘non-legumes’ on five mown pasture sites under organic management in north-eastern Germany. We found no significant difference between the phosphorus content of aboveground biomass of legumes and the associated non-legume group. However, we detected a significant difference between the soil PDL contents of these two groups with lower contents in soils of the legume patches whereas the different P fractions and thus different P availability on the mineral site could not explain the occurrence of legumes. Contrary to reports by many ecologists, we could not confirm a clear relationship between soil phosphorus and species number

Experimental verification of calculated lattice relaxations around impurities in CdTe

We have measured the lattice distortion around As acceptor and Br donor in CdTe with fluorescence detected X ray absorption spectroscopy. We could experimentally verify the lattice relaxation with a bond length reduction of 8 around the As atom as inferred indirectly from ab initio calculations of the electric field gradient performed with the WIEN97 package in comparison with the measured value in a Perturbed Angular Correlation experiment as recently reported. We have complemented our own calculations of relaxation with WIEN97 with calculations using the FHI96md pseudo potential program which allows the use of larger super cell sizes. Encouraged by the good agreement between experiment and model calculation for As in CdTe as well as similarly for the isovalent Se in CdTe, we extended our investigation to Br in CdTe, where the electric field gradient has also been measured, and could not only verify the derived lattice expansion around Br with our EXAFS analysis but additionally observe fractions of Br in the A center as well as in a DX center configuratio

Gaming with eutrophication: Contribution to integrating water quantity and quality management at catchment level

The Metropolitan Region of Sao Paulo (MRSP) hosts 18 million inhabitants. A complex system of 23 interconnected reservoirs was built to ensure its water supply. Half of the potable water produced for MRSP's population (35 m3/s) is imported from a neighbour catchment, the other half is produced within the Alto Tietê catchment, where 99% of the population lives. Perimeters of land use restriction were defined to contain uncontrolled urbanization, as domestic effluents were causing increasing eutrophication of some of these reservoirs. In the 90's catchment committees and sub committees were created to promote discussion between stakeholders and develop catchment plans. The committees are very well structured "on paper". However, they are not very well organised and face a lack of experience. The objective of this work was to design tools that would strengthen their discussion capacities. The specific objective of the AguAloca process was to integrate the quality issue and its relation to catchment management as a whole in these discussions. The work was developed in the Alto Tietê Cabeceiras sub-catchment, one of the 5 sub catchments of the Alto-Tietê. It contains 5 interconnected dams, and presents competitive uses such as water supply, industry, effluent dilution and irrigated agriculture. A RPG was designed following a companion modelling approach (Etienne et al., 2003). It contains a friendly game-board, a set of individual and collective rules and a computerized biophysical model. The biophysical model is used to simulate water allocation and quality processes at catchment level. It articulates 3 modules. A simplified nutrient discharge model permits the estimation of land use nutrient exportation. An arc-node model simulates water flows and associated nutrient charges from one point of the hydrographical network to another. The Vollenweider model is used for simulating specific reservoir dynamics. The RPG allows players to make individual and collective decisions related to water allocation and the management of its quality. Impacts of these decisions are then simulated using the biophysical model. Specific indicators of the game are then updated and may influence player's behaviour (actions) in following rounds. To introduce discussions on the management of water quality at a catchment level, an issue that is rarely explicitly dealt with, four game sessions were implemented involving representatives of basin committees and water and sanitation engineers. During the game session, the participants took advantage of the water quality output of the biophysical model to test management alternatives such as rural sewage collection or effluent dilution. The biophysical model accelerated calculations of flows and eutrophication rates that were then returned to the game board with explicit indicators of quantity and quality. Players could easily test decisions impacting on qualitative water processes and visualize the simulation results directly on the game board that was representing a friendly, virtual and simplified catchment. The Agualoca game proved its ability to turn complex water processes understandable for a non totally initiated public. This experience contributed to a better understanding of multiple-use water management and also of joint management of water quality and quantity. (Résumé d'auteur

Human gene copy number spectra analysis in congenital heart malformations

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (≥200 kb) and losses (≥100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P ≤ 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P ≤ 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways

Towards a variational principle for motivated vehicle motion

We deal with the problem of deriving the microscopic equations governing the individual car motion based on the assumptions about the strategy of driver behavior. We suppose the driver behavior to be a result of a certain compromise between the will to move at a speed that is comfortable for him under the surrounding external conditions, comprising the physical state of the road, the weather conditions, etc., and the necessity to keep a safe headway distance between the cars in front of him. Such a strategy implies that a driver can compare the possible ways of his further motion and so choose the best one. To describe the driver preferences we introduce the priority functional whose extremals specify the driver choice. For simplicity we consider a single-lane road. In this case solving the corresponding equations for the extremals we find the relationship between the current acceleration, velocity and position of the car. As a special case we get a certain generalization of the optimal velocity model similar to the "intelligent driver model" proposed by Treiber and Helbing.Comment: 6 pages, RevTeX

Thermodynamic correction of particle concentrations measured by underwing probes on fast flying aircraft

Particle concentration measurements with underwing probes on aircraft are impacted by air compression upstream of the instrument body as a function of flight velocity. In particular for fast-flying aircraft the necessity arises to account for compression of the air sample volume. Hence, a correction procedure is needed to invert measured particle number concentrations to ambient conditions that is commonly applicable for different instruments to gain comparable results. In the compression region where the detection of particles occurs (i.e. under factual measurement conditions), pressure and temperature of the air sample are increased compared to ambient (undisturbed) conditions in certain distance away from the aircraft. Conventional procedures for scaling the measured number densities to ambient conditions presume that the particle penetration speed through the instruments' detection area equals the aircraft speed (True Air Speed, TAS). However, particle imaging instruments equipped with pitot-tubes measuring the Probe Air Speed (PAS) of each underwing probe reveal PAS values systematically below those of the TAS. We conclude that the deviation between PAS and TAS is mainly caused by the compression of the probed air sample. From measurements during two missions in 2014 with the German Gulfstream G-550 (HALO – High Altitude LOng range) research aircraft we develop a procedure to correct the measured particle concentration to ambient conditions using a thermodynamic approach. With the provided equation the corresponding concentration correction factor ξ is applicable to the high frequency measurements of each underwing probe which is equipped with its own air speed sensor (e.g. a pitot-tube). ξ-values of 1 to 0.85 are calculated for air speeds (i.e. TAS) between 60 and 260 m s−1. From HALO data it is found that ξ does not significantly vary between the different deployed instruments. Thus, for the current HALO underwing probe configuration a parameterisation of ξ as a function of TAS is provided for instances if PAS measurements are lacking. The ξ-correction yields higher ambient particle concentration by about 15–25 % compared to conventional procedures – an improvement which can be considered as significant for many research applications. The calculated ξ-values are specifically related to the considered HALO underwing probe arrangement and may differ for other aircraft or instrument geometries. Moreover, the ξ-correction may not cover all impacts originating from high flight velocities and from interferences between the instruments and, e.g., the aircraft wings and/or fuselage. Consequently, it is important that PAS (as a function of TAS) is individually measured by each probe deployed underneath the wings of a fast-flying aircraft

Long-lived states in synchronized traffic flow. Empirical prompt and dynamical trap model

The present paper proposes a novel interpretation of the widely scattered states (called synchronized traffic) stimulated by Kerner's hypotheses about the existence of a multitude of metastable states in the fundamental diagram. Using single vehicle data collected at the German highway A1, temporal velocity patterns have been analyzed to show a collection of certain fragments with approximately constant velocities and sharp jumps between them. The particular velocity values in these fragments vary in a wide range. In contrast, the flow rate is more or less constant because its fluctuations are mainly due to the discreteness of traffic flow. Subsequently, we develop a model for synchronized traffic that can explain these characteristics. Following previous work (I.A.Lubashevsky, R.Mahnke, Phys. Rev. E v. 62, p. 6082, 2000) the vehicle flow is specified by car density, mean velocity, and additional order parameters $h$ and $a$ that are due to the many-particle effects of the vehicle interaction. The parameter $h$ describes the multilane correlations in the vehicle motion. Together with the car density it determines directly the mean velocity. The parameter $a$, in contrast, controls the evolution of $h$ only. The model assumes that $a$ fluctuates randomly around the value corresponding to the car configuration optimal for lane changing. When it deviates from this value the lane change is depressed for all cars forming a local cluster. Since exactly the overtaking manoeuvres of these cars cause the order parameter $a$ to vary, the evolution of the car arrangement becomes frozen for a certain time. In other words, the evolution equations form certain dynamical traps responsible for the long-time correlations in the synchronized mode.Comment: 16 pages, 10 figures, RevTeX

ps7 133 exposure response modelling and exposure safety modelling analyses in two phase ii studies of atacicept in sle

Purpose Atacicept targets the B-cell stimulating factors BLyS and APRIL, and has been shown to reduce SLE disease activity. Methods APRIL-SLE (NCT00624338) and ADDRESS II (NCT01972568) were phase II, multicenter studies in patients (pts) with autoantibody-positive SLE randomised (1:1:1) to weekly SC injections of atacicept (75 or 150 mg) or placebo (PBO). In APRIL-SLE, pts had BILAG A/B flare at Screening that was reduced to BILAG C/D before randomization using corticosteroids; the primary endpoint was BILAG A/B flare over 52 weeks. In ADDRESS II, pts had SLEDAI-2K≥6 at Screening; the primary endpoint was SRI-4 response at Week 24. SLE responder index (SRI)−6 response was analysed post-hoc in high disease activity (HDA; SLEDAI-2K≥10) pts. Population pharmacokinetic (PK) model-derived exposure vs the probability of response (BILAG A/B flare, SRI-4, SRI-6), exploratory analysis of exposure vs safety, and population model simulations of serum IgG were analysed. Results Exposure-response modelling suggests a relationship between atacicept exposure and SLE clinical response [figure 1], including serum IgG changes from baseline. The optimal atacicept exposure was AUCtau,ss ≥~1 mg.hr/mL, which is more achievable with weekly SC doses of atacicept 150 mg than 75 mg across a range of body weights. Body weight-based dosing is unlikely to offer any value over a fixed 150 mg dose, based on comparable predicted clinical response. In HDA pts, greater reductions in serum IgG from baseline corresponded to a higher probability of SRI-6 response. Greater IgG reductions from baseline were associated with higher atacicept exposure; however, even at the highest exposure range, mean IgG reductions did not exceed ~40%. There was no association between serious/severe infections and exposure by PK quartile. Conclusions Exposure-response modelling indicated robust relationships between atacicept exposure and clinical response or IgG levels, supporting the proposed mechanism of action for atacicept. Atacicept 150 mg weekly SC is likely to provide an effective level of exposure with an acceptable safety profile. There was no evidence of an increased risk of severe or serious infections at higher exposures. Based on these results, the 150 mg dose merits further evaluation