831 research outputs found

    Local current distribution at large quantum dots (QDs): a self-consistent screening model

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    We report the implementation of the self-consistent Thomas-Fermi screening theory, together with the local Ohm's law to a quantum dot system in order to obtain local current distribution within the dot and at the leads. We consider a large dot (size >700>700 nm) defined by split gates, and coupled to the leads. Numerical calculations show that the non-dissipative current is confined to the incompressible strips. Due to the non-linear screening properties of the 2DES at low temperatures, this distribution is highly sensitive to external magnetic field. Our findings support the phenomenological models provided by the experimental studies so far, where the formation of the (direct) edge channels dominate the transport.Comment: 6 Pages, 2 Figure

    Detection of respiratory bacterial pathogens causing atypical pneumonia by multiplex Lightmix<sup>®</sup> RT-PCR.

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    Pneumonia is a severe infectious disease. In addition to common viruses and bacterial pathogens (e.g. Streptococcus pneumoniae), fastidious respiratory pathogens like Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella spp. can cause severe atypical pneumonia. They do not respond to penicillin derivatives, which may cause failure of antibiotic empirical therapy. The same applies for infections with B. pertussis and B. parapertussis, the cause of pertussis disease, that may present atypically and need to be treated with macrolides. Moreover, these fastidious bacteria are difficult to identify by culture or serology, and therefore often remain undetected. Thus, rapid and accurate identification of bacterial pathogens causing atypical pneumonia is crucial. We performed a retrospective method evaluation study to evaluate the diagnostic performance of the new, commercially available Lightmix &lt;sup&gt;®&lt;/sup&gt; multiplex RT-PCR assay that detects these fastidious bacterial pathogens causing atypical pneumonia. In this retrospective study, 368 clinical respiratory specimens, obtained from patients suffering from atypical pneumonia that have been tested negative for the presence of common agents of pneumonia by culture and viral PCR, were investigated. These clinical specimens have been previously characterized by singleplex RT-PCR assays in our diagnostic laboratory and were used to evaluate the diagnostic performance of the respiratory multiplex Lightmix &lt;sup&gt;®&lt;/sup&gt; RT-PCR. The multiplex RT-PCR displayed a limit of detection between 5 and 10 DNA copies for different in-panel organisms and showed identical performance characteristics with respect to specificity and sensitivity as in-house singleplex RT-PCRs for pathogen detection. The Lightmix &lt;sup&gt;®&lt;/sup&gt; multiplex RT-PCR assay represents a low-cost, time-saving and accurate diagnostic tool with high throughput potential. The time-to-result using an automated DNA extraction device for respiratory specimens followed by multiplex RT-PCR detection was below 4 h, which is expected to significantly improve diagnostics for atypical pneumonia-associated bacterial pathogens

    On Spectra of Linearized Operators for Keller-Segel Models of Chemotaxis

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    We consider the phenomenon of collapse in the critical Keller-Segel equation (KS) which models chemotactic aggregation of micro-organisms underlying many social activities, e.g. fruiting body development and biofilm formation. Also KS describes the collapse of a gas of self-gravitating Brownian particles. We find the fluctuation spectrum around the collapsing family of steady states for these equations, which is instrumental in derivation of the critical collapse law. To this end we develop a rigorous version of the method of matched asymptotics for the spectral analysis of a class of second order differential operators containing the linearized Keller-Segel operators (and as we argue linearized operators appearing in nonlinear evolution problems). We explain how the results we obtain are used to derive the critical collapse law, as well as for proving its stability.Comment: 22 pages, 1 figur

    Preventing tumor escape by targeting a post-proteasomal trimming independent epitope

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    Adoptive T cell therapy (ATT) can achieve regression of large tumors in mice and humans; however, tumors frequently recur. High target peptide-major histocompatibility complex-I (pMHC) affinity and T cell receptor (TCR)-pMHC affinity are thought to be critical to preventing relapse. Here, we show that targeting two epitopes of the same antigen in the same cancer cells via monospecific T cells, which have similar pMHC and pMHC-TCR affinity, results in eradication of large, established tumors when targeting the apparently subdominant but not the dominant epitope. Only the escape but not the rejection epitope required postproteasomal trimming, which was regulated by IFN-gamma, allowing IFN-gamma-unresponsive cancer variants to evade. The data describe a novel immune escape mechanism and better define suitable target epitopes for ATT

    Eclipsing white dwarf binaries in Gaia and the Zwicky Transient Faaccility

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    Gaia provided the largest ever catalogue of white dwarf stars. We use this catalogue, along with the third public data release of the Zwicky Transient Facility (ZTF), to identify new eclipsing white dwarf binaries. Our method exploits light-curve statistics and the box least-squares algorithm to detect periodic light-curve variability. The search revealed 18 new binaries, of which 17 are eclipsing. We use the position in the Gaia H-R diagram to classify these binaries and find that the majority of these white dwarfs have MS companions. We identify one system as a candidate eclipsing white dwarf–brown dwarf binary and a further two as extremely low-mass white dwarf binaries. We also provide identification spectroscopy for 17 of our 18 binaries. Running our search method on mock light curves with real ZTF sampling, we estimate our efficiency of detecting objects with light curves similar to the ones of the newly discovered binaries. Many more binaries are to be found in the ZTF footprint as the data releases grow, so our survey is ongoing

    Self-gravitating Brownian particles in two dimensions: the case of N=2 particles

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    We study the motion of N=2 overdamped Brownian particles in gravitational interaction in a space of dimension d=2. This is equivalent to the simplified motion of two biological entities interacting via chemotaxis when time delay and degradation of the chemical are ignored. This problem also bears some similarities with the stochastic motion of two point vortices in viscous hydrodynamics [Agullo & Verga, Phys. Rev. E, 63, 056304 (2001)]. We analytically obtain the density probability of finding the particles at a distance r from each other at time t. We also determine the probability that the particles have coalesced and formed a Dirac peak at time t (i.e. the probability that the reduced particle has reached r=0 at time t). Finally, we investigate the variance of the distribution and discuss the proper form of the virial theorem for this system. The reduced particle has a normal diffusion behaviour for small times with a gravity-modified diffusion coefficient =r_0^2+(4k_B/\xi\mu)(T-T_*)t, where k_BT_{*}=Gm_1m_2/2 is a critical temperature, and an anomalous diffusion for large times ~t^(1-T_*/T). As a by-product, our solution also describes the growth of the Dirac peak (condensate) that forms in the post-collapse regime of the Smoluchowski-Poisson system (or Keller-Segel model) for T<T_c=GMm/(4k_B). We find that the saturation of the mass of the condensate to the total mass is algebraic in an infinite domain and exponential in a bounded domain.Comment: Revised version (20/5/2010) accepted for publication in EPJ

    High-affinity T-cell receptor specific for MyD88 L265P mutation for adoptive T-cell therapy of B-cell malignancies

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    BACKGROUND: Adoptive transfer of engineered T cells has shown remarkable success in B-cell malignancies. However, the most common strategy of targeting lineage-specific antigens can lead to undesirable side effects. Also, a substantial fraction of patients have refractory disease. Novel treatment approaches with more precise targeting may be an appealing alternative. Oncogenic somatic mutations represent ideal targets because of tumor specificity. Mutation-derived neoantigens can be recognized by T-cell receptors (TCRs) in the context of MHC-peptide presentation. METHODS: Here we have generated T-cell lines from healthy donors by autologous in vitro priming, targeting a missense mutation on the adaptor protein MyD88, changing leucine at position 265 to proline (MyD88 L265P), which is one of the most common driver mutations found in B-cell lymphomas. RESULTS: Generated T-cell lines were selectively reactive against the mutant HLA-B*07:02-restricted epitope but not against the corresponding wild-type peptide. Cloned TCRs from these cell lines led to mutation-specific and HLA-restricted reactivity with varying functional avidity. T cells engineered with a mutation-specific TCR (TCR-T cells) recognized and killed B-cell lymphoma cell lines characterized by intrinsic MyD88 L265P mutation. Furthermore, TCR-T cells showed promising therapeutic efficacy in xenograft mouse models. In addition, initial safety screening did not indicate any sign of off-target reactivity. CONCLUSION: Taken together, our data suggest that mutation-specific TCRs can be used to target the MyD88 L265P mutation, and hold promise for precision therapy in a significant subgroup of B-cell malignancies, possibly achieving the goal of absolute tumor specificity, a long sought-after dream of immunotherapy

    ‘Brands in Higher Education ; Challenges and Potential Strategies’

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    This study explores the challenges of university branding and the qualities that make university branding different from commercial branding in terms of cultural issues, branding concepts and frameworks and brands architecture. The literature about branding in the university sector is described and viewed in the context of exploratory interviews with fifty five university managers. The results present the differences between university and commercial brandings as well as culture, brand concepts and brand architecture,. The study was conducted in UK universities, but similar issues in many other countries means that the results are comparable internationally. Overall, the findings presented in this research offer a valuable contribution to our understanding of the complexities of higher education branding

    Vibrio gazogenes-dependent disruption of aflatoxin biosynthesis in Aspergillus flavus: the connection with endosomal uptake and hyphal morphogenesis

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    Aflatoxins, a family of fungal secondary metabolites, are toxic and carcinogenic compounds that pose an enormous threat to global food safety and agricultural sustainability. Specifically agricultural products in African, Southeast Asian and hot and humid regions of American countries suffer most damage from aflatoxin producing molds due to the ideal climate conditions promoting their growth. Our recent studies suggest that Vibrio gazogenes (Vg), an estuarine bacterium non-pathogenic to plants and humans, can significantly inhibit aflatoxin biosynthesis in the producers. In this study, we investigated the mechanism underlying Vg-dependent aflatoxin inhibition using the prominent aflatoxin producer, Aspergillus flavus. We show that aflatoxin inhibition upon Vg treatment was associated with fungal uptake of Vg-prodigiosin, a red pigment, which was consistently visible inside fungal hyphae during treatment. The association of prodigiosin with aflatoxin inhibition was further evident as Serratia marcescens, another prodigiosin producer, significantly inhibited aflatoxin, while non-producers like Escherichia coli, Staphylococcus aureus, Vibrio harveyi, and Vibrio fischeri did not. Also, pure prodigiosin significantly inhibited aflatoxin biosynthesis. Endocytosis inhibitors, filipin and natamycin, reduced the Vg-prodigiosin uptake by the fungus leading to a significant increase in aflatoxin production, suggesting that uptake is endocytosis-dependent. The Vg treatment also reduced hyphal fusion (>98% inhibition) and branching, which are both endosome-dependent processes. Our results, therefore, collectively support our theory that Vg-associated aflatoxin inhibition is mediated by an endocytosis-dependent uptake of Vg-prodigiosin, which possibly leads to a disruption of normal endosomal functions
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