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e18929Background: There exists significant variation in lung cancer treatment depending on physician, payer and stage of disease without significant difference in survival or QoL (Quality of Life)....

The greenhouses of solar drying for urban residual sludge represent an economic alternative to the classic thermal dryers. The aim of this study is the modelling with a two-scale approach of the process Solia ™ . A three-dimensional modelling with the software Ansys ® /Fluent ® allows to visualize internal aeraulics and exchanges, and so to underline influent parameters on the process effiency. The systemic zero-dimensional model is developed on Matlab ® /Simulink ® software. It takes into account the previous exchanges and allows a higher physical simulation time, at a day or season scale.

2-Methoxyestradiol (2ME), an end-metabolite of 17beta-estradiol, is an antiproliferative agent that is currently being tested in clinical trials for cancer treatment. We hereby report that sub-cytotoxic concentrations of 2ME influence the in vitro proliferation of human peripheral blood B lymphocytes. More surprisingly, we have observed that 2ME induces the conversion of CD138(-) B lymphocytes into CD138(+) cells of phenotype similar to immunoglobulin (Ig)-secreting plasma cells. Normal human B lymphocytes expressing CD138 increased in response to 2ME in a dose-dependent fashion, from 2% at baseline up to 31% in cells cultured in the presence of 0.75 microM 2ME. Moreover, most of the converted cells were also CD27(+) and secreted high levels of IgG (151 microg/10(6)cells/24h). IEF studies revealed that conversion occurred in a polyclonal manner. We then exploited this effect of 2ME to gain further insights into the molecular mechanisms that govern changes in transcription factors involved in plasma cells differentiation. Plasma cells generated by 2ME treatment of normal human B lymphocytes expressed elevated levels of IRF4 and reduced levels of Pax5 and Bcl-6. Similarly, levels of XBP-1 and Blimp-1 transcripts were increased. Our results suggest that the differentiation of peripheral blood B lymphocytes into plasma cells requires a similar modulation of transcription factors expression that for tonsil and bone marrow B lymphocytes.

Electrons have been accelerated from ultra-thin diamond-like carbon (DLC) foils by an ultrahigh-intensity laser pulse. A distinct quasi-monoenergetic electron spectrum peaked at 30 MeV is observed at a target thickness as thin as 5 nm which is in contrast to the observations of wide spectral distributions for thicker targets. At the same time, a substantial drop in laser-accelerated ion energies is found. The experimental findings give first indication that relativistic electron sheets can be generated from ultra-thin foils which in future may be used to generate brilliant X-ray beams by the coherent reflection of a second laser.

The ultra-high fields of high-power short-pulse lasers are expected to contribute to understanding fundamental properties of the quantum vacuum and quantum theory in very strong fields. For example, the neutral QED vacuum breaks down at the Schwinger field strength of 1.3×1018 V/m, where a virtual e+e- pair gains its rest mass energy over a Compton wavelength and materializes as a real pair. At such an ultra-high field strength, an electron experiences an acceleration of aS=2×1028g and hence fundamental phenomena such as the long predicted Unruh effect start to play a role. The Unruh effect implies that the accelerated electron experiences the vacuum as a thermal bath with the Unruh temperature. In its accelerated frame the electron scatters photons off the thermal bath, corresponding to the emission of an entangled pair of photons in the laboratory frame. While it remains an experimental challenge to reach the critical Schwinger field strength within the immediate future even in view of the enormous thrust in high-power laser developments in recent years, the near-future laser technology may allow to probe the signatures of the Unruh effect mentioned above. Using a laser-accelerated electron beam (γ∼300) and a counter-propagating laser beam acting as optical undulator should allow to create entangled Unruh photon pairs (i.e., signatures of the Unruh effect) with energies of the order of several hundred keV. An even substantially improved experimental scenario can be realized by using a brilliant 20 keV photon beam as X-ray undulator together with a low-energy (γ≈2) electron beam. In this case the separation of the Unruh photon pairs from background originating from linearly accelerated electrons (classical Larmor radiation) is significantly improved. Detection of the Unruh photons may be envisaged by Compton polarimetry in a 2D-segmented position-sensitive germanium detector.

Several human histo-blood groups are glycosphingolipids, including P/P1/P(k). Glycosphingolipids are implicated in HIV-host-cell-fusion and some bind to HIV-gp120 in vitro. Based on our previous studies on Fabry disease, where P(k) accumulates and reduces infection, and a soluble P(k) analog that inhibits infection, we investigated cell surface-expressed P(k) in HIV infection. HIV-1 infection of peripheral blood-derived mononuclear cells (PBMCs) from otherwise healthy persons, with blood group P(1)(k), where P(k) is overexpressed, or blood group p, that completely lacks P(k), were compared with draw date-matched controls. Fluorescence-activated cell sorter analysis and/or thin layer chromatography were used to verify P(k) levels. P(1)(k) PBMCs were highly resistant to R5 and X4 HIV-1 infection. In contrast, p PBMCs showed 10- to 1000-fold increased susceptibility to HIV-1 infection. Surface and total cell expression of P(k), but not CD4 or chemokine coreceptor expression, correlated with infection. P(k) liposome-fused cells and CD4(+) HeLa cells manipulated to express high or low P(k) levels confirmed a protective effect of P(k). We conclude that P(k) expression strongly influences susceptibility to HIV-1 infection, which implicates P(k) as a new endogenous cell-surface factor that may provide protection against HIV-1 infection.

Summaryc-Src is the normal human cellular protein homologue of the viral oncogene v-src. c-Src activity was reported recently to increase in CD40-activated human B lymphocytes, suggesting its involvement in proliferation. To elucidate the exact role of c-Src in this process, we investigated the effects of c-Src over-expression on normal B lymphocyte growth. B lymphocytes purified from human peripheral blood were infected with Ad5/F35 vector encoding either a constitutively active c-Src (c-Src/dominant-positive) or a dominant-negative c-Src (c-Src/DN). Little variation of B lymphocytes expansion could be observed between control enhanced yellow fluorescent protein and c-Src/dominant-positive-infected cells. In contrast, over-expression of c-Src/DN results in a 40% inhibition of B lymphocyte expansion. These results suggest that DN c-Src may compete with endogenous c-Src, resulting in partial inhibition of a transcriptional pathway involved in B lymphocyte proliferation. We demonstrate further that c-Src can phosphorylate signal transducer and activator of transcription 5b (STAT5b) on tyrosine 699 and that c-Src and STAT5b co-associate during B lymphocyte proliferation. These results confirm an important role for c-Src in the expansion of normal human B lymphocytes in vitro, in which c-Src may regulate STAT5b in the intracellular signalling pathway important for the proliferation of normal human B lymphocytes.

Model-based diagnosis compares observations from a system with predictions using a mathematical model to detect and isolate faulty components. Analyzing which faults that can be detected and isolat ...

We study effects of classical magnetic impurities on the Anderson metal-insulator transition numerically. We find that a small concentration of Heisenberg impurities enhances the critical disorder amplitude $W_{\rm c}$ with increasing exchange coupling strength $J$. The resulting scaling with $J$ is analyzed which supports an anomalous scaling prediction by Wegner due to the combined breaking of time-reversal and spin-rotational symmetry. Moreover, we find that the presence of magnetic impurities lowers the critical correlation length exponent $\nu$ and enhances the multifractality parameter $\alpha_0$. The new value of $\nu$ improves the agreement with the value measured in experiments on the metal-insulator transition (MIT) in doped semiconductors like phosphor-doped silicon, where a finite density of magnetic moments is known to exist in the vicinity of the MIT. The results are obtained by a finite-size scaling analysis of the geometric mean of the local density of states which is calculated by means of the kernel polynomial method. We establish this combination of numerical techniques as a method to obtain critical properties of disordered systems quantitatively., Comment: 5 pages, 2 figures, 2 tables, submitted to PRB

A model-based misfire detection algorithm is proposed. The algorithm is able to detect misfires and identify the failing cylinder during different conditions, such as cylinder-to-cylinder variations, cold starts, and different engine behavior in different operating points. Also, a method is proposed for automatic tuning of the algorithm based on training data. The misfire detection algorithm is evaluated using data from several vehicles on the road and the results show that a low misclassification rate is achieved even during difficult conditions. (C) 2014 Elsevier Ltd. All rights reserved. Funding Agencies|Volvo Car Corporation; Swedish Research Council within the Linnaeus Center CADICS

Local changes in the topology of electricity grids can cause overloads far away from the disturbance, making the prediction of the robustness against changes in the topology - for example caused by power outages or grid extensions - a challenging task. The impact of single-line additions on the long-range response of DC electricity grids has recently been studied. By solving the real part of the static AC load flow equations, we conduct a similar investigation for AC grids. In a regular 2D grid graph with cyclic boundary conditions, we find a power law decay for the change of power flow as a function of distance to the disturbance over a wide range of distances. The power exponent increases and saturates for large system sizes. By applying the same analysis to the German transmission grid topology, we show that also in real-world topologies a long-ranged response can be found., Comment: 12 pages, 16 figures, submitted to PRE

A number of residual generation methods have been developed for robust model-based fault detection and isolation (FDI). There have also been a number of offline (i.e., design-time) methods that focus on optimizing FDI performance (e.g., trading off detection performance versus cost). However, design-time algorithms are not tuned to optimize performance for different operating regions of system behavior. To do this, would need to define online measures of sensitivity and robustness, and use them to select the best residual set online as system behavior transitions between operating regions. In this paper we develop a quantitative measure of residual performance, called the detectability ratio that applies to additive and multiplicative uncertainties when determining the best residual set in different operating regions. We discuss this methodology and demonstrate its effectiveness using a case study.

Diagnostic for investigating and distinguishing different laser ion acceleration mechanisms has been developed and successfully tested. An ion separation wide angle spectrometer can simultaneously investigate three important aspects of the laser plasma interaction: (1) acquire angularly resolved energy spectra for two ion species, (2) obtain ion energy spectra for multiple species, separated according to their charge to mass ratio, along selected axes, and (3) collect laser radiation reflected from and transmitted through the target and propagating in the same direction as the ion beam. Thus, the presented diagnostic constitutes a highly adaptable tool for accurately studying novel acceleration mechanisms in terms of their angular energy distribution, conversion efficiency, and plasma density evolution.

Vectors carrying the origin of replication (oriP) and driving expression of the EBNA-1 protein from Epstein–Barr virus (EBV) replicate as extrachromosomal episomes in human cells. Whether these vectors can be maintained as episomes in murine cells is still controversial. Here we demonstrate that EBNA-1 expression alone was unable to maintain episomal expression of an EBV-based vector in the murine Sp2/0 cell line. However, we were able to obtain long-term episome maintenance in Sp2/0 cells after exogenously expressing human EBP2 by genetic engineering. Our results provide further evidence for the fundamental role of human EBP2 in episomal maintenance of EBV-based vectors. Moreover, we demonstrate that EBV-based vectors can be successfully used in cells presumably incompetent for episomal maintenance.Key words: EBV vector, EBNA-1, EBP2, episomal maintenance, mouse cell, Sp2/0 myeloma cell line.

Background To examine the effect of office-based duplex-guided balloon-assisted maturation (DG-BAM) on arteriovenous fistula (AVF), we retrospectively analyzed our experience. Methods Over the past 10 months, we performed 185 DG-BAMs (range, 1–8 procedures; mean, 3.7) in 45 patients (29 male, 16 female; mean age, 68.2 ± 12.8 years) with 31 radial–cephalic, 7 brachial–cephalic, and 7 brachial–basilic AVFs. Balloon sizes (3–10 mm) were chosen based on duplex measurements (1–2 mm larger than minimal vein diameter). Forearm AVFs were dilated to 8 mm, and arm AVFs were dilated to 10 mm. Results All cases but one (99.5%) were successfully dilated. This exception was a large AVF rupture that required surgical repair. AVFs failed to mature in seven of the remaining 44 patients (16%) despite DG-BAM because of proximal vein stenoses (PVS). Four patients had cephalic arch stenoses, and three had proximal subclavian vein stenoses. Arm AVFs were more commonly associated with PVS (6 of 14 patients, 43%) as compared with the ones placed in the forearm (1 of 30 patients, 3.3%), with a P value of 0.0024. All these seven AVFs subsequently matured after successful balloon angioplasty of the venous outflow. Conclusions These data suggest that office-based DG-BAM of AVFs is feasible, safe, and averts nephrotoxic contrast and radiation. PVS appear to be the most common cause of failure for AVFs subjected to BAM. Because arm AVFs are at increased risk of PVS, we suggest that a careful duplex evaluation of the outflow be performed in these cases and in all AVFs that fail to mature.

A novel method for characterising the full spectrum of deuteron ions emitted by laser driven multi-species ion sources is discussed. The procedure is based on using differential filtering over the detector of a Thompson parabola ion spectrometer, which enables discrimination of deuterium ions from heavier ion species with the same charge-to-mass ratio (such as C6+, O8+, etc.). Commonly used Fuji Image plates were used as detectors in the spectrometer, whose absolute response to deuterium ions over a wide range of energies was calibrated by using slotted CR-39 nuclear track detectors. A typical deuterium ion spectrum diagnosed in a recent experimental campaign is presented., 7 pages, 7 figures

We study the effects of classical magnetic impurities on the Anderson metal-insulator transition (AMIT) numerically. In particular we find that while a finite concentration of Ising impurities lowers the critical value of the site-diagonal disorder amplitude Wc, in the presence of Heisenberg impurities, Wc is first increased with increasing exchange coupling strength J due to time-reversal symmetry breaking. The resulting scaling with J is compared to analytical predictions by Wegner [1]. The results are obtained numerically, based on a finite-size scaling procedure for the typical density of states [2], which is the geometric average of the local density of states. The latter can efficiently be calculated using the kernel polynomial method [3]. Although still suffering from methodical shortcomings, our method proves to deliver results close to established results for the orthogonal symmetry class [4]. We extend previous approaches [5] by combining the KPM with a finite-size scaling analysis. We also disc...

Emerging approaches to short-pulse laser-driven neutron production offer a possible gateway to compact, low cost, and intense broad spectrum sources for a wide variety of applications. They are based on energetic ions, driven by an intense short-pulse laser, interacting with a converter material to produce neutrons via breakup and nuclear reactions. Recent experiments performed with the high-contrast laser at the Trident laser facility of Los Alamos National Laboratory have demonstrated a laser-driven ion acceleration mechanism operating in the regime of relativistic transparency, featuring a volumetric laser-plasma interaction. This mechanism is distinct from previously studied ones that accelerate ions at the laser-target surface. The Trident experiments produced an intense beam of deuterons with an energy distribution extending above 100 MeV. This deuteron beam, when directed at a beryllium converter, produces a forward-directed neutron beam with ∼5 × 109 n/sr, in a single laser shot, primarily due to ...

CD30 and its counter-receptor CD30 ligand (CD30L) are members of the TNF-receptor/TNFalpha superfamily and function to regulate lymphocyte survival and differentiation. Several monoclonal antibodies (MAbs) have been developed against CD30 and, based on mutual inhibition assays, are grouped into three nonoverlapping serologic clusters. However, the relationship between the epitopes recognized by the antibodies comprising each cluster and the binding domain for CD30L is not known. Using a soluble CD30L/CD8alpha chimeric protein, we assessed the ability of anti-CD30 MAb to inhibit the binding of CD30L to CD30 expressed by the CD30+ Karpas 299 cell line. CD30L binding by CD30 is blocked by MAb that recognize epitopes belonging to cluster Group A (like Ber-H2, Ber-H8, and HRS-4) as well as cluster Group C (like HeFi-1 and M44). Cluster Group B antibodies, including M67 and Ki-1, do not affect CD30L binding to CD30. The pattern of CD30L binding inhibition shows only limited correspondence to the functional capacity of some anti-CD30 MAb to trigger CD30 signaling. Finally, we demonstrate that the anti-CD30L MAb M81 also completely inhibits CD30/CD30L interaction. This information is useful for applying these MAbs in functional studies to further investigate the CD30/CD30L system and for designing assays for soluble CD30L.

The scaled boundary finite element method (SBFEM) is a semi-analytical method in which only the boundary is discretized. The results on the boundary are scaled into the domain with respect to a scaling center which must be “visible” from the whole boundary. For beam-like problems the scaling center can be selected at infinity and only the cross-section is discretized. Two new elements for thin-walled beams have been developed on the basis of the first order shear deformation theory. The beam sections are considered to be multilayered laminate plates with arbitrary layup. The arbitrary cross-section is discretized with beam elements of Timoshenko type. Using the virtual work principle gives the SBFEM equation, which is a system of differential equations of a gyroscopic type. The solution is calculated using the matrix exponential function. The elements have been tested and compared with a finite element model and they give good results. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)

Autosomal recessive limb girdle muscular dystrophy (LGMD2) is a clinically and genetically heterogenous group of diseases involving at least six different loci. Five genes have already been identified: calpain-3 at LGMD2A (15q15), and four members of the sarcoglycan (SG) complex, alpha-SG at LGMD2D (17q21), beta-SG at LGMD2E (4q12), gamma-SG at LGMD2C (13q12), and delta-SG at LGMD2F (5q33-q34). The gene product at LGMD2B (2p13-p16) is still unknown and at least one other gene is still unmapped. We investigated 20 Turkish families (18 consanguineous) diagnosed as having LGMD2. Most of our patients had onset of symptoms before age 10. The phenotypes varied from severe to benign. We analyzed the SG complex by immunofluorescence and/or western blot. Genotyping was performed using markers defining the six known loci and the suspected genes were screened for mutations. Six of 17 index cases showed deficiency of the SG complex, by immunofluorescence and/or western blot. Seven cases involved one of the known genes of the SG complex (alpha, 2; beta, 1; and gamma, 4 cases), and five mutations were documented in the alpha- and gamma-SG genes. After linkage analysis, 10 families were characterized as having LGMD2A (calpain-3 deficiency), and all mutations were eventually identified. One family was classified as having LGMD2B and 1 family that has normal SGs was linked to the chromosome 5q33-q34 locus (LGMD2F). In 1 family there was no linkage to any of the known LGMD2 loci. It appears that in Turkey, there is a broad spectrum of genes and defects involved in LGMD2. It may be possible to correlate genotype to phenotype in LGMD2. All severe cases belonged to the gamma-SG-deficiency group. Nine calpain-3-deficient cases had intermediate and 1 had moderate clinical courses. The LGMD2B patient had a moderate clinical expression, whereas the LGMD2F case was truly benign.

Dystroglycan is a cell surface complex which in muscle links the extracellular matrix protein laminin-2 to the membrane associated cytoskeletal protein dystrophin. Recently it was found that dystroglycan is also expressed in developing epithelial cells. Moreover, antibodies against dystroglycan can perturb epithelial cell development in kidney organ culture. Dystroglycan could provide a link between the basement membrane and the intracellular space also in epithelial cells. However, there is no dystrophin in epithelial cells. Byin situhybridization here we show prominent expression of a shorter isoform of dystrophin, Dp140, in embryonic kidney tubules. In addition, another isoform, Dp71, is expressed by all studied embryonic epithelial cells. Both isoforms share the dystroglycan-binding region of dystrophin but lack the region known to bind to actin. Here we also characterized monoclonal antibodies against different domains of dystrophin and used these to study the distribution of Dp140 protein. In embryonic kidney tubules the dystrophin antibody VIA42A3 stained an intracellular antigen close to the basal cells. In contrast, no staining was observed in adult kidney. We suggest that Dp140 is a structural component during kidney tubulogenesis but it may also be involved in signal transduction.

Here we present experimental results on laser-driven ion accel- eration from relativistically transparent, overdense plasmas in the break-out afterburner (BOA) regime. Experiments were preformed at the Trident ultra-high contrast laser facility at Los Alamos National Laboratory, and at the Texas Petawatt laser facility, located in the University of Texas at Austin. It is shown that when the target becomes relativistically transparent to the laser, an epoch of dramatic acceleration of ions occurs that lasts until the electron density in the expanding target reduces to the critical density in the non-relativistic limit. For given laser parameters, the optimal target thickness yielding the highest maximum ion energy is one in which this time window for ion acceleration overlaps with the intensity peak of the laser pulse. A simple analytic model of relativistically induced transparency is presented for plasma expansion at the

Experimental data are presented for laser-driven carbon C6+ ion-acceleration, verifying 2D-PIC studies for multi-species targets in the Break-Out Afterburner regime. With Trident's ultra-high contrast at relativistic intensities of 5 × 1020 W/cm2 and nm-scale diamond targets, acceleration of carbon ions has been optimized by using target laser-preheating for removal of surface proton contaminants. Using a high-resolution wide angle spectrometer, carbon C6+ ion energies exceeding 1 GeV or 83 MeV/amu have been measured, which is a 40% increase in maximum ion energy over uncleaned targets. These results are consistent with kinetic plasma modeling and analytic theory.

We present experimental data and PIC simulations on laser driven ion acceleration in the relativistic transparent regime. We measured carbon C6+ ions energies exceeding 1GeV and proton energies exceeding 100MeV. Conversion efficiency of laser light into ions, beam shape and scaling laws are presented for this regime and compared to the Target Normal Sheath acceleration and Radiation pressure acceleration regime.

Fourth-order cross-correlation of the laser pulse is obtained from the spectral interferogram produced from the laser pulse and a self-created reference pulse. High dynamic range contrast measurement (60 dB) is demonstrated by measuring an imposed pre-pulse.

The sarcoglycan complex is known to be involved in limb-girdle muscular dystrophy (LGMD) and is composed of at least three proteins: alpha-, beta-, and gamma-sarcoglycan. delta-Sarcoglycan has now been identified as a second 35-kDa sarcolemmal transmembrane glycoprotein that shares high homology with gamma-sarcoglycan and is expressed mainly in skeletal and cardiac muscle. Biochemical analysis has demonstrated that gamma- and delta-sarcoglycan are separate entities within the sarcoglycan complex and that all four sarcoglycans exist in the complex on a stoichiometrically equal basis. Immunohistochemical analysis of skeletal muscle biopsies from patients with LGMD2C, LGMD2D, and LGMD2E demonstrated a reduction of the entire sarcoglycan complex in these muscular dystrophies. Furthermore, we have mapped the human delta-sarcoglycan gene to chromosome 5q33-q34 in a region overlapping the recently linked autosomal recessive LGMD2F locus.

We report adhalin deficiency in 8 patients with clinically diagnosed muscular dystrophy, dystrophic histopathological features, high plasma creatine kinase levels, normal expression of dystrophin, and marked variability of symptoms. Although the distribution of hyposthenia was similar in all 8 patients and predominantly involved muscles in the pelvic girdle, age at onset and rate of disease progression were highly variable: In 2 patients onset, at ages 24 and 25, was later than has been previously observed. We found no apparent relation between disease severity and the quantity of adhalin expressed. Two kinds of myopathy with adhalin deficiency have been reported: one caused by a mutation in the adhalin gene on chromosome 17 (primary adhalinopathy) and the other linked to chromosome 13. The product of the gene on chromosome 13 is probably associated with adhalin and its deficiency results in secondary adhalinopathy. The severity of clinical phenotypes in these adhalinopathies seems to relate more to the kind and site of the mutations than to the residual amount of the protein. We also detected a variable reduction in the laminin beta 1 subunit by immunohistochemistry in most patients, confirming that this is commonly associated with adhalin deficiency.

We study the (Anderson) metal-insulator transition (MIT) in tight binding models (TBM) of disordered systems using the scaling behavior of the typical density of states (GDOS) as localization criterion. The GDOS is obtained as the geometrical mean value of the local density of states (LDOS) averaged over many different lattice sites and disorder realizations. The LDOS can efficiently be obtained within the kernel polynomial method (KPM). To check the validity and accuracy of the method, we apply it here to the standard Anderson model of disordered systems, for which the results (for instance for the critical disorder strength of the Anderson transition) are well known from other methods.

Neutrons are unique particles to probe samples in many fields of research ranging from biology to material sciences to engineering and security applications. Access to bright, pulsed sources is currently limited to large accelerator facilities and there has been a growing need for compact sources over the recent years. Short pulse laser driven neutron sources could be a compact and relatively cheap way to produce neutrons with energies in excess of 10 MeV. For more than a decade experiments have tried to obtain neutron numbers sufficient for applications. Our recent experiments demonstrated an ion acceleration mechanism based on the concept of relativistic transparency. Using this new mechanism, we produced an intense beam of high energy (up to 170 MeV) deuterons directed into a Be converter to produce a forward peaked neutron flux with a record yield, on the order of ${10}^{10}\text{ }\text{ }\mathrm{n}/\mathrm{sr}$. We present results comparing the two acceleration mechanisms and the first short pulse laser generated neutron radiograph.

Dystroglycan is a novel laminin receptor that links the extracellular matrix and sarcolemma in skeletal muscle. The dystroglycan complex containing alpha- and beta-dystroglycan also serves as an agrin receptor in muscle, where it may regulate agrin-induced acetylcholine receptor clustering at the neuromuscular junction. beta-Dystroglycan has now been expressed in vitro and shown to directly interact with Grb2, an adapter protein involved in signal transduction and cytoskeletal organization. Protein binding assays with two Grb2 mutants, Grb2/P49L and Grb2/G203R, which correspond to the loss-of-function mutants in the Caenorhabditis elegans sem-5, demonstrated that the dystroglycan-Grb2 association is through beta-dystroglycan C-terminal proline-rich domains and Grb2 Src homology 3 domains. Affinity chromatography has also shown endogenous skeletal muscle Grb2 interacts with beta-dystroglycan. Immunoprecipitation experiments have demonstrated that Grb2 associates with alpha/beta-dystroglycan in vivo in both skeletal muscle and brain. The specific dystroglycan-Grb2 interaction may play an important role in extracellular matrix-mediated signal transduction and/or cytoskeleton organization in skeletal muscle that may be essential for muscle cell viability.

Syntrophin represents three cytoplasmic components of the dystrophin-glycoprotein complex that links the cytoskeleton to the extracellular matrix in skeletal muscle. alpha-Syntrophin has now been translated in vitro and shown to associate directly with all three components of the syntrophin triplet and with dystrophin. The in vitro translated 71-kDa non-muscle dystrophin isoform, containing the cystein-rich/C-terminal domain, can also interact with the syntrophin triplet. The syntrophin binding motif in dystrophin was localized to exons 73 and 74 including amino acids 3447-3481 by comparing the interactions of alpha-syntrophin and seven overlapping human dystrophin fusion proteins. More than one syntrophin interaction site in this binding motif was suggested. alpha-Syntrophin also interacts directly with a C-terminal utrophin fusion protein. alpha-Syntrophin is localized to the muscle sarcolemma as well as to the neuromuscular junction in control mouse muscle. However, similar to utrophin, alpha-syntrophin is only present at the neuromuscular junction in mdx mouse muscle in which dystrophin is absent. Our data suggest that alpha-syntrophin binds all syntrophin isoforms, and syntrophin directly interacts with dystrophin through more than one binding site in dystrophin exons 73 and 74 including amino acids 3447-3481.

Neutrons are a unique tool to alter and diagnose material properties and excite nuclear reactions with a large field of applications. It has been stated over the last years, that there is a growing need for intense, pulsed neutron sources, either fast or moderated neutrons for the scientific community. Accelerator based spallation sources provide unprecedented neutron fluxes, but could be complemented by novel sources with higher peak brightness that are more compact. Lasers offer the prospect of generating a very compact neutron source of high peak brightness that could be linked to other facilities more easily. We present experimental results on the first short pulse laser driven neutron source powerful enough for applications in radiography. For the first time an acceleration mechanism (BOA) based on the concept of relativistic transparency has been used to generate neutrons. This mechanism not only provides much higher particle energies, but also accelerated the entire target volume, thereby circumventing the need for complicated target treatment and no longer limited to protons as an intense ion source. As a consequence we have demonstrated a new record in laser-neutron production, not only in numbers, but also in energy and directionality based on an intense deuteron beam. The beam contained, for the first time, neutrons with energies in excess of 100 MeV and showed pronounced directionality, which makes then extremely useful for a variety of applications. The results also address a larger community as it paves the way to use short pulse lasers as a neutron source. They can open up neutron research to a broad academic community including material science, biology, medicine and high energy density physics as laser systems become more easily available to universities and therefore can complement large scale facilities like reactors or particle accelerators. We believe that this has the potential to increase the user community for neutron research largely.

We report experimental evidence for a Rayleigh-Taylor-like instability driven by radiation pressure of an ultraintense (${10}^{21}\text{ }\text{ }\mathrm{W}/{\mathrm{cm}}^{2}$) laser pulse. The instability is witnessed by the highly modulated profile of the accelerated proton beam produced when the laser irradiates a 5 nm diamondlike carbon (90% C, 10% H) target. Clear anticorrelation between bubblelike modulations of the proton beam and transmitted laser profile further demonstrate the role of the radiation pressure in modulating the foil. Measurements of the modulation wavelength, and of the acceleration from Doppler-broadening of back-reflected light, agree quantitatively with particle-in-cell simulations performed for our experimental parameters and which confirm the existence of this instability.

Investigation of the molecular processes that control the development and function of lymphocytes is essential for our understanding of humoral immunity, as well as lymphocyte-associated pathogenesis. Adenovirus-mediated gene transfer provides a powerful tool for investigating these processes. However, we observed variation in transgene expression among normal human peripheral blood B lymphocytes from different donors and at distinct stages of differentiation. It is recognized that efficient gene transfer is highly dependent on the intracellular route by which the viruses travel within the host cell. Thus, we aimed to examine this aspect in the present study.We analyzed the binding, uptake, intracellular trafficking and fate of CY3-labelled Ad5/F35 vectors in lymphoid cell lines and primary B cells. Furthermore, we decreased protein synthesis levels and rapid endocytosis in a plasma cell line exhibiting a high level of protein synthesis activity and activated transcription and endocytosis in primary B cells, which are less active than plasma cells.Major differences in intracellular trafficking pattern between B cells and plasma cell line U266 were identified that explain the observed divergence in transgene expression efficiency. Importantly, modification of the transcriptional or translational activity of U266 cells reverted the Ad5/F35 endocytic trafficking to that seen in B cells, with a loss of transgene expression, whereas activation of B cells with phorbol 12-myristate 13-acetate had the opposite effects.Taken together, these results suggest that Ad5/F35 is more efficiently transduced in cells with a strong transcriptional activity as a result of differences in intracellular trafficking. This finding extends our current knowledge of the mechanisms of adenovirus-mediated gene transfer.

In the last few years several multi-view display systems appeared increasing in size and the number of views that can be displayed. The increasing number of views allow for more realistic content with a high level of detail and complex lighting. For highest quality the images of synthetic scenes are usually ray traced. For large displays that are able to resolve a large amount of different views the number of viewing rays is enormous and it would take several month to render the content via ray tracing. One solution is to render only a few images and interpolate the remaining images with an image based rendering approach. This work introduces an algorithm that selects the best viewpoints for an image based rendering algorithm on the basis of given criteria. Special care is taken to cover occlusions and account for the dimension and angular resolution of multi-view displays.

Background Venous outflow obstruction may play a role in patients with chronic venous stasis symptoms who fail to improve despite conventional modalities of treatment that focus on the reflux component of the disease with little attention to the possibility of an obstructive component. The introduction of minimally invasive venous stenting using venography and intravenous ultrasonography (IVUS) provides the ability to treat the “obstructive” component of the disease. Methods We undertook a retrospective review of 56 limbs in 53 patients with chronic venous stasis symptoms. Initial transcutaneous Doppler ultrasonographic evaluation of the inferior vena cava, iliac, femoral, greater saphenous, and perforator veins was performed looking for any evidence of deep venous thrombosis, superficial venous thrombosis, perforator veins, and reflux (location and degree). Afterword, the patients were managed in the conventional fashion (leg elevation, compression, and great saphenous vein (GSV) and perforator ablation, if present) for a period of 3 months. If ulcer healing was not noted, iliac-femoral venography and IVUS were undertaken. A significant stenosis was defined as a 50% reduction in vein cross-sectional area as measured by IVUS. 1,2,3 Stenotic lesions were managed with stenting followed by balloon angioplasty. Patients were followed up for ulcer healing or improvement of stasis symptoms. Results Of the 56 limbs, 10 (17.8%) had postthrombotic changes, 7 (12.5%) had incompetent perforators, and 27 (48.2%) had an incompetent superficial venous system. In the stented group ( n = 29), 3 limbs had perforator ablation alone, 13 limbs had GSV ablation alone, and 1 limb had both perforator and GSV ablation. In the unstented group ( n = 27), 10 limbs had GSV ablation alone, and 3 limbs had both perforator and GSV ablation. The overall incidence of deep reflux was 51.8%; 17 of 29 limbs (58.6%) in the stented group had evidence of deep reflux, and 12 of 27 limbs (44.4%) in the unstented group had deep reflux. All venograms except one (98.2%) were performed under local anesthesia with sedation. The procedure was performed in an ambulatory setting in 69.6% (39 of 56) of the limbs. CEAP clinical severity class distribution was as follows: C2, 4%; C3, 16%; C4, 18%; C5, 5%; C6, 57%. Over half of the limbs (29 of 56) were found to have stenotic lesions and required stenting. Eight patients (11 limbs) did not return for ulcer healing assessment. The majority (19 of 29) of limbs in the stented group had a CEAP of 6. Among the patients with CEAP 6 who returned for follow-up ( n = 26), 7 had no evidence of stenosis and required no stenting. Only one of those (14.3%) healed his ulcers after 3 months (average follow-up of 4.8 months). The remainder 19 limbs were found to have stenotic lesions and underwent stenting. The ulcers healed in 11 of those (58%) over a period of 1 week to 8 months (average of 5 months), with average follow-up of 3.6 months ( p = 0.08). The cumulative primary and secondary patency rates were 93.1% (27 of 29) and 100% (29 of 29), respectively. Two stent thromboses occurred within 4 weeks of the initial procedure. Both occurred in patients with postthrombotic obstruction. One patient developed a superficial femoral artery pseudoaneurysm. Conclusion Over half of our patients with open ulcers had stenotic lesions. The ulcers healed in 58% of the stented limbs. That indicates that outflow obstruction may play a significant role in patients with chronic venous stasis symptoms, especially those with open ulcers who failed to respond to other treatment modalities. The procedure itself is relatively safe and simple and can be performed on an ambulatory basis.

Recently a new display type has emerged that is able to display 50,000 views offering a full parallax autostereoscopic view of static scenes. With the advancement in the manufacturing technology, multi-view displays come with more and more views of dynamic content, closing the gap to this high quality full parallax display. The established method of content generation for synthetic stereo images is to render both views. To ensure a high quality these images are often ray traced. With the increasing number of views, rendering of all views is not feasible for multi-view displays. Therefore methods are required that can render the large amount of different views required by those displays efficiently. In the following a complete solution is presented that describes how all views for a full parallax display can be rendered from a small set of input images and their associated depth images with an image-based rendering algorithm. An acceleration of the rendering of two orders of magnitude is achieved by different parallelization techniques and the use of efficient data structures. Moreover, the problem of finding the best-next-view for an image-based rendering algorithm is addressed and a solution is presented that ranks possible viewpoints based on their suitability for an image-based rendering algorithm.

Relevant to laser based electron/ion accelerations, a single shot second harmonic generation frequency resolved optical gating (FROG) system has been developed to characterize laser pulses (80 J, ∼600 fs) incident on and transmitted through nanofoil targets, employing relay imaging, spatial filter, and partially coated glass substrates to reduce spatial nonuniformity and B-integral. The device can be completely aligned without using a pulsed laser source. Variations of incident pulse shape were measured from durations of 613 fs (nearly symmetric shape) to 571 fs (asymmetric shape with pre- or postpulse). The FROG measurements are consistent with independent spectral and autocorrelation measurements.

Greenhouses of solar sludge drying are developed as an economical alternative to the classic thermal dryers. In this study, two complementary models are used to observe and predict the operation of Solia™ units at different time and space scales. A 3D model informs on solar aspects and internal profiles of the multi-physical phenomena. A 0D model integrates drying kinetics and a new approach in stratified windrow in order to forecast the drying cycle efficiency on a large time scale. These tools are confronted to experimental data acquired on a Solia™ unit located in Fonsorbes (France).

Gene transfer applications with adenovirus (Ad) type 5 are limited by its native tropism, hampering their use in several cell types. To address this limitation, several Ad vectors bearing chimeric fiber have been produced to take advantage of the different cellular receptors used by other subgroups of Ads. In this study, we have compared the transduction efficiency of Ad5 and the chimeric Ad5/F35 in primary human B lymphocytes and B-cell lines as a function of the developmental stage. We found that transduction efficiencies of the two Ads differ independently of their targeted cellular receptor but are related to the intracellular localization of the virus. In efficiently transduced cells, Ads were localized in early endosomes or cytosol, whereas in poorly transduced cells they were localized within late endosomes/lysosomes. Finally, we demonstrate that treatment of cells with phosphatase inhibitors known to redirect endocytosis towards caveolae, increased Ad5/F35 transduction efficiency.

We present experimental studies on ion acceleration from ultrathin diamondlike carbon foils irradiated by ultrahigh contrast laser pulses of energy 0.7 J focused to peak intensities of $5\ifmmode\times\else\texttimes\fi{}{10}^{19}\text{ }\text{ }\mathrm{W}/{\mathrm{cm}}^{2}$. A reduction in electron heating is observed when the laser polarization is changed from linear to circular, leading to a pronounced peak in the fully ionized carbon spectrum at the optimum foil thickness of 5.3 nm. Two-dimensional particle-in-cell simulations reveal that those ${\mathrm{C}}^{6+}$ ions are for the first time dominantly accelerated in a phase-stable way by the laser radiation pressure.

We report on the acceleration of ion beams from ultrathin diamondlike carbon foils of thickness 50, 30, and 10 nm irradiated by ultrahigh contrast laser pulses at intensities of $\ensuremath{\sim}7\ifmmode\times\else\texttimes\fi{}{10}^{19}\text{ }\text{ }\mathrm{W}/{\mathrm{cm}}^{2}$. An unprecedented maximum energy of 185 MeV ($15\text{ }\text{ }\mathrm{MeV}/\mathrm{u}$) for fully ionized carbon atoms is observed at the optimum thickness of 30 nm. The enhanced acceleration is attributed to self-induced transparency, leading to strong volumetric heating of the classically overdense electron population in the bulk of the target. Our experimental results are supported by both particle-in-cell (PIC) simulations and an analytical model.

The acceleration of electrons from ultra-thin foils using high-intensity lasers has recently gained high interest due to the outstanding characteristics of the generated electron beam observed in particle-in-cell simulations. Here, the generation of a relativistic electron bunch of ultra-high density was demonstrated which may be well-suited for the generation of ultra-short coherent x-ray radiation via Thomson back-scattering2.

The high contrast front-end for the 200 TW Trident laser has shown in recent experiments the importance roles that Amplified Spontaneous Emission (ASE) and prepulse contrast play in laser-ion acceleration. Ion energies above 58 MeV with efficiencies of greater than 5% into ions above 4 MeV have been observed even at modest intensities, on par with the Nova Petawatt results2 at half the intensity1, and a fifth of the energy and power, at an intrinsic laser ASE contrast of ≫ 10−7. Scalings for, laser energy, intensity, and target thickness are presented and compared to other empirical scalings and theories, including results of the new ultra-high contrast ≫10−10 Optical Parametric Chirped-Pulse Amplification (OPCPA) front-end system3.