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The requirements for broadband photodetection are becoming exceedingly demanding in hyperspectral imaging. While intrinsic photoconductor arrays based on mercury cadmium telluride represent the most sensitive and suitable technology, their optical spectrum imposes a narrow spectral range with a sharp absorption edge that cuts their operation to <25 μm. Here we demonstrate a large ultra-broadband photoconductivity in twisted double bilayer graphene heterostructures spanning the spectral range of 2–100 μm with internal quantum efficiencies of approximately 40% at speeds of 100 kHz. The large response originates from unique properties of twist-decoupled heterostructures including pristine, crystal field-induced terahertz band gaps, parallel photoactive channels and strong photoconductivity enhancements caused by interlayer screening of electronic interactions by respective layers acting as sub-atomic spaced proximity screening gates. Our work demonstrates a rare instance of an intrinsic infrared–terahertz photoconductor that is complementary metal-oxide-semiconductor compatible and array integratable, and introduces twist-decoupled graphene heterostructures as a viable route for engineering gapped graphene photodetectors with three-dimensional scalability.Thanks to the unique properties of twisted double bilayer graphene heterostructures, an ultra-broadband photoconductivity spanning the spectral range of 2–100 μm with internal quantum efficiencies of approximately 40% at speeds of 100 kHz is reported.

General relativity (GR) extensions based on renormalization group (RG) flows may lead to scale-dependent couplings with nontrivial effects at large distance scales. Here we develop further the approach in which RG effects at large distance scales are fully encoded in an effective action and we apply it to cosmology. In order to evaluate the cosmological consequences, our main assumption is the use of a RG scale such that the (infrared) RG effects only appear at perturbative order (not at the background level). The emphasis here is on analytical results and qualitative understanding of the implied cosmology. We employ commonly used parametrizations for describing modified gravity in cosmology (as the slip parameter). From them, we describe the dynamics of the first order perturbations and estimate bounds on the single dimensionless parameter ( ν ) introduced by this framework. Possible impacts on dark matter and dark energy are discussed. It is also shown here that the ν parameter effects to f σ 8 are stronger at low redshifts ( z < 1.5 ), while different values for ν do not appreciably change f σ 8 at higher redshifts, thus opening a window to alleviate an issue that is currently faced by Λ CDM.

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Objectives To evaluate technical feasibility and oncologic and functional outcomes of three different surgical procedures of nerve-sparing radical cystectomy (NS-RC) for the treatment of organ-confined bladder cancer at a single referral centre. Materials and methods All consecutive cases of NS-RC carried out between 1997 and 2012 were retrospectively analysed. NS-RC included nerve-sparing cysto-vesicleprostatectomy (NS-CVP), capsule-sparing cystectomy (CS-C) and seminal-sparing cysto-prostatectomy (SS-CP). Peri-operative parameters and post-operative outcomes were analysed. Results Overall, 90 patients underwent NS-RC, 35 (38.9 %) of whom received a NS-CVP, while 36 (40 %) and 19 (21.1 %) underwent capsule CS-C and SS-CP, respectively. No difference was registered comparing oncologic outcomes of the three different techniques; however, two local recurrences after CS-C were attributed to the surgical technique. Complete post-operative daytime and night-time urinary continence (UC) at 24 and 48 months was achieved in 94.4 and 74.4 % and in 88.8 and 84.4 % of cases, respectively. CS-C showed both the best UC and sexual function preservation rate at early follow-up (24 months). Overall, a satisfactory post-operative erectile function (IIEF-5 ≥ 22) was proved in 57 (68.6 %) and 54 (65.0 %) patients at 24 and 48 months, respectively. Significant difference was found when comparing sexual function preservation rate of NS-CVP (28.5 %) to that of CS-C (91.6 %) and SS-CP (84.2 %). Conclusion NS-RC for male patients accounted for 7.4 % of overall radical cystectomy. To a limited extent of the selected organ-confined bladder cancers treated, the three different procedures analysed showed comparable results in terms of local recurrence and cancer-specific survival. Both CS-C and SS-CP procedures provided excellent functional outcomes when compared to original NS-CVP.

Background and purpose: Chemokine receptors CXCR1 and CXCR2 may mediate influx of neutrophils in models of acute and chronic inflammation. The potential benefits of oral administration of a CXCR1/2 inhibitor, DF 2162, in adjuvant‐induced polyarthritis (AIA) were investigated. Experimental approach: A model of AIA in rats was used to compare the therapeutic effects of the treatment with DF2162, anti‐TNF or anti‐CINC‐1 antibodies on joint inflammation and local production of cytokines and chemokines. Key results: DF2162 prevented chemotaxis of rat and human neutrophils induced by chemokines acting on CXCR1/2. DF2162 was orally bioavailable and metabolized to two major metabolites. Only metabolite 1 retained CXCR1/2 blocking activity. Treatment with DF2162 (15 mg kg−1, twice daily) or metabolite 1, but not metabolite 2, starting on day 10 after arthritis induction diminished histological score, the increase in paw volume, neutrophil influx and local production of TNF, IL‐1β, CCL2 and CCL5. The effects of DF2162 were similar to those of anti‐TNF, and more effective than those of anti‐CINC‐1, antibodies. DF2162 prevented disease progression even when started 13 days after arthritis induction. Conclusions and implications: DF 2162, a novel orally‐active non‐competitive allosteric inhibitor of CXCR1 and CXCR2, significantly ameliorates AIA in rats, an effect quantitatively and qualitatively similar to those of anti‐TNF antibody treatment. These findings highlight the contribution of CXCR2 in the pathophysiology of AIA and suggest that blockade of CXCR1/2 may be a valid therapeutic target for further studies aiming at the development of new drugs for treatment of rheumatoid arthritis. British Journal of Pharmacology (2008) 153, 992–1002; doi:10.1038/sj.bjp.0707462; published online 24 September 2007

Activation of complement via the innate and adaptive immune system is vital to the bodys defences in fighting infections. Unregulated complement activation is likely to play a crucial role in the pathogenesis of several diseases including psoriasis, adult (acute) respiratory distress syndrome (ARDS), bullous pemphigoid (BP), rheumatoid arthritis (RA) and ischemia-reperfusion (I / R) injury. The 74 amino acid peptide C5a is released after complement activation at sites of inflammation and is a potent chemoattractant for neutrophils, basophils, eosinophils, leukocytes, monocytes and macrophages. Recombinant proteins and humanized anti-C5 antibodies have been recently developed for blocking specific proteins of the complement system bringing renewed attention towards complement inhibition. Pharmacological studies have been highlighting the complement fragment C5a as an interesting target for the management of complement mediated diseases. Specific inhibition of C5a biological activity could gain therapeutic benefit without affecting the protective immune response. In the last few years several peptide and non-peptide antagonists of C5a have been discovered and tested in relevant pharmacological models; the availability of orally active compounds is rapidly helping to delineate the precise role of C5a in immunoinflammatory disorders. Moreover, mutagenesis data for the C5a / C5a receptor (C5aR) couple make C5aR a valuable model for mechanistic studies of peptidergic G-protein coupled receptors (GPCRs). The aim of this review is to outline the recent advances in C5a inhibition, especially highlighting the value of a multidisciplinary integrated approach in drug discovery.

Background and purpose: Neutrophil migration into tissues is involved in the genesis of inflammatory pain. Here, we addressed the hypothesis that the effect of CXC chemokines on CXCR1/2 is important to induce neutrophil migration and inflammatory hypernociception. Experimental approach: Mice were treated with a non‐competitive allosteric inhibitor of CXCR1/2, DF 2162, and neutrophil influx and inflammatory hypernociception were assessed by myeloperoxidase assay and electronic pressure meter test, respectively, in various models of inflammation. Key results: DF 2162 inhibited neutrophil chemotaxis induced by CXCR1/2 ligands but had no effect on CXCL8 binding to neutrophils. A single mutation of the allosteric site at CXCR1 abrogated the inhibitory effect of DF 2162 on CXCL‐8‐induced chemotaxis. Treatment with DF 2162 prevented influx of neutrophils and inflammatory hypernociception induced by CXCL1 in a dose‐dependent manner. The compound inhibited neutrophil influx and inflammatory hypernociception induced by carrageenan, lipopolysaccharide and zymosan, but not hypernociception induced by dopamine and PGE2. DF 2162 had a synergistic effect with indomethacin or the absence of TNFR1 to abrogate carrageenan‐induced hypernociception. Treatment with DF 2162 diminished neutrophil influx, oedema formation, disease score and hypernociception in collagen‐induced arthritis. Conclusions and implications: CXCR1/2 mediates neutrophil migration and is involved in the cascade of events leading to inflammatory hypernociception. In addition to modifying fundamental pathological processes, non‐competitive allosteric inhibitors of CXCR1/2 may have the additional benefit of providing partial relief for pain and, hence, may be a valid therapeutic target for further studies aimed at the development of new drugs for the treatment of rheumatoid arthritis. British Journal of Pharmacology (2008) 154, 460–470; doi:10.1038/bjp.2008.94; published online 24 March 2008

Cases of drugs being withdrawn have been triggered mainly by manufacturing authorisation holders rather than by regulatory authorities.7 Therefore doubts have been expressed worldwide on the capability of pharmacovigilance systems to detect safety signals and to take swift action, and on the transparency of regulatory agencies to provide effective information on drug safety.8 The new legislation1 provides the possibility to add conditions to marketing authorisations to meet specific obligations by the applicant (ie, studies, registries, etc) as part of a risk-management plan, and these conditions have to be made public.

This work proposes a committee of Cascade Correlation neural networks as an online smoother for random measurement noise. The goals of this paper are twofold: first it intends to explore the possibilities of using a constructive neural network algorithm to learn how to filter typical noisy data from a bioreactor, CO 2 mol fractions of the effluent gas during the aerobic cultivation of Bacillus megaterium to produce the enzyme penicillin G acylase. Second, to propose a committee of such networks for achieving more realistic results, capturing the inherent trend of the process. In order to do that this paper discusses the advantages of using a constructive neural network algorithm, describes how the committee of NNs operates and evaluates its performance using real CO 2 online data obtained in laboratorial experiments. The paper also presents results obtained with classical filtering algorithms, for comparison.

In France, more than 80% of human congenital toxoplasmosis is attributable to Toxoplasma gondii strains belonging to the type-II lineage, whereas 3 main lineages have been described in Europe. Cell invasion, parasite replication, and cyst formation of type-II strains isolated from congenital infections were compared in a human cell model. The phenotype patterns of the 4 type-II strains studied differed from each other; the 2 strains responsible for asymptomatic infection formed significantly fewer cysts than the 2 strains isolated from symptomatic toxoplasmosis. The capacity to form cysts was different among the type-II strains studied and may be related to the clinical form.