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Most model-based diagnosis approaches reported in the literature adopt a generic architecture and approach. However, the fault hypotheses generated by these methods may differ. This is not only due to the methods, but also on the basic assumptions made by different diagnostic algorithms on fault manifestation and evolution. While comparing different diagnosis approaches, the assumptions made in each case will have a significant effect on fault diagnosability performance and must therefore also be taken into consideration. Thus, to make a fair comparison, the different approaches should be designed based on the same assumptions. This paper studies the relation between a set of commonly made assumptions and fault isolability performance in order to compare different diagnosis approaches. As a case study, five developed diagnosis systems for a wind turbine benchmark problem are evaluated to analyze the type of assumptions that are applied in the different designs.

To be able to evaluate quantitative fault diagnosability performance in model-based diagnosis is useful during the design of a diagnosis system. Different fault realizations are more or less likely ...

This paper presents a framework for distributed fault detection and isolation in dynamic systems. Our approach uses the dynamic model of each subsystem to derive a set of independent, local diagnosers. If needed, the subsystem model is extended to include measurements and model equations from its immediate neighbors to compute its diagnosis. Our approach is designed to ensure that each subsystem diagnoser provides the correct results, therefore, a local diagnosis result is equivalent to the results that would be produced by a global system diagnoser. We discuss the distribute diagnosis algorithm, and illustrate its application using a multi-tank system.

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The present paper proposes an advanced approach for Polymer Electrolyte Membrane Fuel Cell (PEMFC) systems fault detection and isolation through a model-based diagnostic algorithm. The considered algorithm is developed upon a lumped parameter model simulating a whole PEMFC system oriented towards automotive applications. This model is inspired by other models available in the literature, with further attention to stack thermal dynamics and water management. The developed model is analysed by means of Structural Analysis, to identify the correlations among involved physical variables, defined equations and a set of faults which may occur in the system (related to both auxiliary components malfunctions and stack degradation phenomena). Residual generators are designed by means of Causal Computation analysis and the maximum theoretical fault isolability, achievable with a minimal number of installed sensors, is investigated. The achieved results proved the capability of the algorithm to theoretically detect and isolate almost all faults with the only use of stack voltage and temperature sensors, with significant advantages from an industrial point of view. The effective fault isolability is proved through fault simulations at a specific fault magnitude with an advanced residual evaluation technique, to consider quantitative residual deviations from normal conditions and achieve univocal fault isolation.

BACKGROUND During early HIV-1 infection of CD4 T-lymphocytes, many host protein tyrosine kinases become activated within minutes, including phosphoprotein pp60 (c-Src) and the focal adhesion kinase family member, proline-rich tyrosine kinase 2 (Pyk2). Whether their activation facilitates or impedes infection remains to be determined. METHODS c-Src kinase inhibitors (SU6656, PP1, and PP2), adenovectors [wild-type and dominant-negative (DN) c-src] or siRNA (targeting c-src or pyk2) were used to inhibit, compete with or knockdown c-Src in Jurkat C, Jurkat E6-1, Hut 78 or Kit225 T-cell lines. Cells were then infected with HIV-1 luciferase reporter virus expressing VSV-G or HXB2(X4) envelope, and luciferase activity was measured after 2 days. Reverse transcriptase activity and viral cDNA were measured 1 hour after infection, whereas integrated virus was measured 12 hours after infection. RESULTS Pretreating Jurkat T-cells with SU6656 led to increased VSV-G luciferase activity. In the adenovector experiments, T-cells overexpressing dominant-negative c-Src, but not wild-type c-Src, showed increased luciferase activity after VSV-G infection. siRNA knockdown of c-Src or Pyk2, followed by HXB2 infection in Jurkat T-cells, lead to increased reverse transcriptase activity, viral cDNA, integrated virus, and increased luciferase activity. CONCLUSIONS Pyk2 is known to interact with c-Src. Thus, Pyk2 activation that coincides with increased c-Src activity during HIV-1 infection could be responsible for c-Src activation. Reduced c-Src activation increases HIV-1 reverse transcription, integration, and/or transcription, suggesting the high c-Src activity seen early in HIV-1 infection may be a cellular response to slow or prevent early infection in CD4 T-cells.

A hybrid diagnosis system design is proposed that combines model-based and data-driven diagnosis methods for fault isolation. A set of residuals are used to detect if there is a fault in the system and a consistency-based fault isolation algorithm is used to compute all diagnosis candidates that can explain the triggered residuals. To improve fault isolation, diagnosis candidates are ranked by evaluating the residuals using a set of one-class support vector machines trained using data from different faults. The proposed diagnosis system design is evaluated using simulations of a model describing the air-flow in an internal combustion engine.

A generalized fault isolability matrix is proposed for quantitative analysis of fault isolability properties. The original fault isolability matrix gives information about which faults that are isolable from each other. However, other relavant isolability properties are not visible which can be important, for example, information regarding alternative fault hypotheses and multiple-fault isolability. The result of the analysis can be presented in the same compact form as the existing fault isolability matrix which makes it simple to visualize. As a case study, a model of an internal combustion engine is analyzed and two different solutions to the test selection problem are compared.

In this paper, we solve the local gathering problem of a swarm of $n$ indistinguishable, point-shaped robots on a two dimensional grid in asymptotically optimal time $\mathcal{O}(n)$ in the fully synchronous $\mathcal{FSYNC}$ time model. Given an arbitrarily distributed (yet connected) swarm of robots, the gathering problem on the grid is to locate all robots within a $2\times 2$-sized area that is not known beforehand. Two robots are connected if they are vertical or horizontal neighbors on the grid. The locality constraint means that no global control, no compass, no global communication and only local vision is available; hence, a robot can only see its grid neighbors up to a constant $L_1$-distance, which also limits its movements. A robot can move to one of its eight neighboring grid cells and if two or more robots move to the same location they are \emph{merged} to be only one robot. The locality constraint is the significant challenging issue here, since robot movements must not harm the (only globally checkable) swarm connectivity. For solving the gathering problem, we provide a synchronous algorithm -- executed by every robot -- which ensures that robots merge without breaking the swarm connectivity. In our model, robots can obtain a special state, which marks such a robot to be performing specific connectivity preserving movements in order to allow later merge operations of the swarm. Compared to the grid, for gathering in the Euclidean plane for the same robot and time model the best known upper bound is $\mathcal{O}(n^2)$., Comment: arXiv admin note: substantial text overlap with arXiv:1510.05454

Sudden failure of a single transmission element in a power grid can induce a domino effect of cascading failures, which can lead to the isolation of a large number of consumers or even to the failure of the entire grid. Here we present results of the simulation of cascading failures in power grids, using an alternating current (AC) model. We first apply this model to a regular square grid topology. For a random placement of consumers and generators on the grid, the probability to find more than a certain number of unsupplied consumers decays as a power law and obeys a scaling law with respect to system size. Varying the transmitted power threshold above which a transmission line fails does not seem to change the power law exponent $q \approx 1.6$. Furthermore, we study the influence of the placement of generators and consumers on the number of affected consumers and demonstrate that large clusters of generators and consumers are especially vulnerable to cascading failures. As a real-world topology we consider the German high-voltage transmission grid. Applying the dynamic AC model and considering a random placement of consumers, we find that the probability to disconnect more than a certain number of consumers depends strongly on the threshold. For large thresholds the decay is clearly exponential, while for small ones the decay is slow, indicating a power law decay., Comment: submitted to Phys. Rev. E, 7 pages, 7 figures

Extreme ultraviolet and X-ray radiation can be generated when the high harmonics of incident laser light are reflected by a dense plasma, the so-called relativistically oscillating mirror mechanism. Theoretical studies have, however, predicted an alternative regime in which short-wavelength light is generated by dense electron nanobunches that form at the plasma–vacuum boundary. Signatures of this coherent synchrotron emission are now experimentally observed.

Background To identify patients with pulmonary embolism (PE) without deep venous thrombosis (DVT), and to compare them with those with an identifiable source on upper (UED) and lower-extremity venous duplex scans (LED). Methods We performed a retrospective review of 2700 computed tomography angiograms of the chest between January 2008 and September 2010 and identified 230 patients with PE. We then evaluated the results of UED and LED and divided the patients into four groups based on the results of their duplex studies. We compared patients with PE and DVT with those with PE and no DVT in terms of age, gender, size and location of PE, critical illness, malignancy, and in-hospital mortality. Results We identified 152 women and 78 men (mean age, 68 years) with PE. One hundred thirty-one patients had a documented source of PE (group 1). Fifty-three patients had negative LED results, but did not undergo UED (group 2). Thirty-one patients did not undergo either LED or UED (group 3). Seven men and eight women had no documented source of PE on UED and LED (group 4). Ten of 15 patients in group 4 had a documented malignancy listed as one of their diagnoses. Because patients in groups 2 and 3 did not undergo complete duplex studies, we excluded them from our analysis. We then reviewed the discharge summaries of patients in groups 1 and 4. There was no statistically significant difference in age and gender distribution, size and location of PE, critical illness, smoking status, cardiovascular disease, trauma, and in-hospital mortality between patients in group 1 and 4. Patients in group 4 had a statistically significant increased prevalence of malignancy (67% vs. 40%, P = 0.046). Patients in group 4 also had a higher percentage of active cancer than those in group 1 (47% vs. 24%, P = 0.084), although not statistically significant. We defined active cancer as either a metastatic disease or a malignancy diagnosed shortly before or after the diagnosis of PE. Patients who were undergoing treatment for cancer at the time of diagnosis of PE were also considered to have active cancer. Conclusion We demonstrated a statistically significant increased prevalence of malignancy in patients with PE without DVT. However, pathophysiology and clinical significance are the aspects that remain to be understood after accrual of more patients and further research. Possibilities such as de novo thrombosis of pulmonary arteries, complete dislodgement of thrombi from peripheral veins, or false-negative venous duplex need to be explored.

When electrons are accelerated to near light-speeds through an overdense plasma by an intense laser beam, the usually opaque plasma becomes optically transparent. High-speed laser experiments provide unprecedented insight into the dynamics of this process.

In addition to its classical CD40 receptor, CD154 also binds to αIIbβ3, α5β1, and αMβ2 integrins. Binding of CD154 to these receptors seems to play a key role in the pathogenic processes of chronic inflammation. This investigation was aimed at analyzing the functional interaction of CD154 with CD40, αIIbβ3, and α5β1 receptors. We found that the binding affinity of CD154 for αIIbβ3 is ∼4-fold higher than for α5β1. We also describe the generation of sCD154 mutants that lost their ability to bind CD40 or αIIbβ3 and show that CD154 residues involved in its binding to CD40 or αIIbβ3 are distinct from those implicated in its interaction to α5β1, suggesting that sCD154 may bind simultaneously to different receptors. Indeed, sCD154 can bind simultaneously to CD40 and α5β1 and biologically activate human monocytic U937 cells expressing both receptors. The simultaneous engagement of CD40 and α5β1 activates the mitogen-activated protein kinases, p38, and extracellular signal-related kinases 1/2 and synergizes in the release of inflammatory mediators MMP-2 and -9, suggesting a cross-talk between these receptors.

Investigation of the molecular processes which 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 provided a powerful tool to investigate these processes. We have previously demonstrated that adenoviral vector Ad5/F35 transduces plasma cell lines at a higher efficiency than primary B cells, owing to differences in intracellular trafficking. Given that phosphatases are effectors of intracellular trafficking, here we have analyzed the effects of a panel of phosphatase inhibitors on Ad5/F35 transduction efficiency in B lymphocytes in the present study. FACS analysis was conducted to determine Ad5/F35-EYFP transduction efficiency in lymphoid cells, including human primary B cells, following serine/threonine phosphatase (PSP) inhibitor treatment. We further used confocal microscopy to analyze intracellular trafficking and fate of CY3 labeled Ad5/F35 vectors, in PSP treated lymphoid cell. Finally, we analyzed the MAPK pathway by Western blot in PSP treated cells. Adenoviral transduction efficiency was unresponsive to inhibition of PP1 whereas inhibition of PP2A by cantharidic acid, or PP1 and PP2A by okadaic acid, substantially increased transduction efficiency. Importantly, confocal microscopy analyses revealed that inhibition of PP2A shut down adenovirus recycling. Moreover, inhibition of PP2A resulted in increased phosphorylation of AKT, ERK1/2 and MEK1/2. Taken together, these results suggest that Ad5/F35 is more efficiently transduced in cells following PP2A inhibition. Our results are in agreement with reports indicating that PP2A is involved in the formation of recycling vesicles and might be of interest for gene therapy applications.

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.

Advancement of ion acceleration by intense laser pulses is studied with ultra-thin nanometer-thick diamond like carbon and micrometer-thick Titanium target foils. Both investigations aim at optimizing the electron density distribution which is the key for efficient laser driven ion acceleration. While recently found maximum ion energies achieved with ultra-thin foils mark record values micrometer thick foils are flexible in terms of atomic constituents. Electron recirculation is one prerequisite for the validity of a very simple model that can approximate the dependence of ion energies of nanometer-thick targets when all electrons of the irradiated target area interact coherently with the laser pulse and Coherent Acceleration of Ions by Laser pulses (CAIL) becomes dominant. Complementary experiments, an analytical model and particle in cell computer simulations show, that with regard to ultra-short laser pulses (duration ~45 fs at intensities up to 5 × 1019 W/cm2) and a micrometer-thick target foil with higher atomic number a close to linear increase of ion energies manifests in a certain range of laser intensities.

Ultrathin (o 5 nm) self-supporting diamond-like carbon (DLC) foils are prepared by filtered cathodic vacuum arc (FCVA) deposition method as targets for laser-driven ion acceleration. The thickness and the morphology of these foils are characterized by atomic force microscope (AFM) and scanning electron microscope (SEM).

In this paper we report on an experimental study of high harmonic radiation generated in nanometer-scale foil targets irradiated under normal incidence. The experiments constitute the first unambiguous observation of odd-numbered relativistic harmonics generated by the v × B component of the Lorentz force verifying a long predicted property of solid target harmonics. Simultaneously the observed harmonic spectra allow in-situ extraction of the target density in an experimental scenario which is of utmost interest for applications such as ion acceleration by the radiation pressure of an ultraintense laser.

Background 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. Methods 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. Results 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. Conclusions 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. Copyright © 2011 John Wiley & Sons, Ltd.

In this paper the route towards the current optimum of laser generated ion beams by subsequently changing the important parameters such as target thickness, laser pulse contrast, angle of incidence and laser pulse polarization is sketched. Beginning with parameters of isothermal target normal sheath acceleration (TNSA), we reached the regime where the plasma expansion can be described adiabatically and results in a symmetric ion acceleration. Further we demonstrated a way to phase match the accelerating electron population with the ions, namely coherent acceleration of ions by laser pulses (CAIL), which finally lead to radiation pressure acceleration (RPA) if the laser polarization was changed from linear to circular. These findings of ion acceleration with transparent solid targets are additionally supported by analyzing the optical properties of the transmitted laser pulse (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Background The technique of long segment stenting of the superficial femoral artery (SFA) has been associated with poorer short- and long-term results. The full metal jacket (FMJ) stenting is typically described as long segment continuous stenting of a vessel segment. Initially, this technique was described in percutaneous coronary interventions. However, until recently, FMJ of the SFA has not been studied. We examined our experience with FMJ of the SFA to evaluate the outcomes and the safety of this technique. Methods Retrospective data were gathered for peripheral angioplasties and stenting for the period between January 2005 and December 2008. The cases involving FMJ stenting of the SFA were identified by angiographic findings and the operative dictations providing the stent data. Selective FMJ stenting of the SFA was performed for the residual stenosis after balloon angioplasty of the SFA because of either dissection or significant recoil. The cases with concomitant iliac artery angioplasty and/or stenting were excluded from the data set for analysis. The variables for the evaluation were primary patency rate, mortality rate, and limb salvage rate, which were stratified on the basis of the risk factors. Results A total of 63 cases involving FMJ stenting of the SFA were identified from the database of 707 patients who had peripheral endovascular interventions between January 2005 and December 2008. Average age of the patients was 70 years (range: 52-104 years, SD: 10.1 years). There were no transatlantic inter-society consensus (TASC) A lesions, 11% (7/63) of the lesions were TASC B, 68% (43/63) were TASC C, and 21% (13/63) were TASC D. The median primary patency rate was 9 months (95% CI: 5.06-12.94). The mortality rate was 4% at 6-month follow-up. The limb salvage rate was 85.7%. In all, 65% (41/63) of the patients were claudicants, whereas 23% (15/63) had intervention for some form of tissue loss (ischemic ulcer, gangrene). Associated infrapopliteal intervention was performed in 15.9% of the patients. Average creatinine level was 1.67 (range: 0.7-10.9, SD: 2.03) and 49% (31/63) of the patients had diabetes. The average 6-month patency rate was 55% (SD: 0.5). Multivariate logistic regression analysis showed that diabetes (OR: 0.33, p = 0.044, 95% CI: 0.11-0.97) and a creatinine level of ≥1.6 (OR: 0.16, p = 0.038, 95% CI: 0.03-0.9) were the independent risk factors for loss of patency in Conclusion Our experience suggests promising results for the technique of FMJ of the SFA and also that further examination of the technique is warranted.

Introduction La technique de stenting long d’un segment de l’artere femorale superficielle (AFS) a ete associee a des resultats mediocres a court et long termes. Le full metal jacket (FMJ) stenting est typiquement decrit comme le stenting continu d’un long segment vasculaire. Au debut, cette technique a ete decrite dans les interventions coronaires percutanees. Cependant, jusqu’a recemment, le FMJ de l’AFS n’a pas ete etudie. Nous avons examine notre experience de FMJ de l’AFS afin d’evaluer les resultats et la surete de cette technique. Methodes Les donnees retrospectives etaient recueillies concernant les angioplasties peripheriques avec stenting sur la periode de janvier 2005 a decembre 2008. Les cas impliquant un stenting en FMJ de l’AFS etaient identifies par les resultats angiographiques et les comptes-rendus operatoires fournissant les donnees du stent. Le stenting selectif en FMJ de l’AFS etait realise pour une stenose residuelle apres angioplastie au ballon de l’AFS en raison d’une dissection ou d’un recoil significatif. Les cas d’angioplastie concomitante et/ou stenting de l’artere iliaque etaient exclus des donnees analysees. Les criteres d’evaluation etaient les taux primaires de permeabilite, taux de mortalite, et taux de sauvetage de membre, qui etaient stratifiees sur la base des facteurs de risque. Resultats Un total de 63 cas impliquant un stenting en FMJ de l’AFS ont ete identifies dans la base de donnees de 707 patients qui avaient eu des interventions endovasculaires peripheriques entre janvier 2005 et decembre 2008. L’âge moyen des patients etait de 70 ans (extremes : 52-104 ans, ecart-type : 10,1 ans). Il n’y avait aucune lesion TASC A, 11% (7/63) des lesions etaient TASC B, 68% (43/63) etaient TASC C, et 21% (13/63) etaient TASC D. Le taux primaire median de permeabilite etait de 9 mois (IC a 95% : 5,06-12,94). Le taux de mortalite etait de 4% au cours du suivi de six mois. Le taux de sauvetage de membre etait de 85,7%. En tout, 65% (41/63) des patients etaient des claudicants, tandis que 23% (15/63) ont eu une intervention pour un trouble trophique (ulcere, gangrene ischemique). Une intervention sous poplitee associee a ete effectuee dans 15,9% des patients. Le niveau moyen de creatininemie etait de 1,67 (extremes : 0,7-10,9, ecart-type : 2,03) et 49% (31/63) des patients etaient diabetiques. Le taux moyen a six mois de permeabilite etait de 55% (ecart-type : 0,5). L’analyse de regression logistique multivariee montrait que le diabete (OR : 0,33, p = 0,044, IC a 95% : 0,11-0,97) et un niveau de creatininemie ≥ 1,6 (OR : 0,16, p = 0,038, ic a 95% : 0,03-0,9) etaient des facteurs de risque independants de thrombose Conclusion Notre experience suggere des resultats prometteurs de la technique de FMJ de l’AFS, et d’autres etudes sur cette technique sont justifiees.

PAX5 is an essential transcription factor for the commitment of lymphoid progenitors to the B-lymphocyte lineage. PAX5 suppression results in retrodifferentiation of B lymphocytes to an uncommitted progenitor cell stage, whereas PAX5 suppression in mature B lymphocytes leads to further development into plasma cells. Here, we have analyzed the fate of plasma cell lines following PAX5 reexpression. Human B cell lines were infected with Ad5/F35 adenoviruses encoding either EYFP or PAX5. Expression analysis of specific plasma cell transcription factors (IRF4, Blimp-1 and XBP-1) suggests that PAX5 reexpression does not induce retrodifferentiation of plasma cells into B lymphocytes. Interestingly, the viability of RPMI-8226 and U266 multiple myeloma cell lines markedly declined at 4-7 days post-transduction, whereas other plasma cell lines maintained their viability. Apoptosis analysis through Annexin V measurement also revealed a higher level of apoptosis in PAX5-expressing myeloma cell lines. Finally, Western blot analysis of pro- and anti-apoptotic proteins revealed that the anti-apoptotic protein MCL-1 was down-modulated in PAX5-transduced multiple myeloma cell lines. In conclusion, our results show that the expression of PAX5 in plasma cell lines induces apoptosis exclusively in multiple myelomas. This might represent a potential therapeutic avenue in the treatment of multiple myeloma.

e19010Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have revolutionized the treatment of acute promyelocytic leukemia (APML). Anthracycline is added at induction for high ri...

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.

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.

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.

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