Phase Separation in Rapid Solidified Ag-rich Ag-Cu-Zr Alloys

The microstructure and phase formation of rapid solidified Ag-rich Ag-Cu-Zr alloys were investigated. Two types of structure; interconnected- and droplet-type structures, were obtained due to phase separation mechanisms. The former was spinodal decomposition and the later was nucleation and growth mechanism. Depending on the alloy compositions, three crystalline phases; FCC-Ag, AgZr and Cu10Zr7 phases were observed along with an in-situ nanocrystalline/amorphous composite. Vickers hardness testing indicated a significant increase of hardness in the nanocrystalline/amorphous-composite alloy

Crowdcloud: A Crowdsourced System for Cloud Infrastructure

The widespread adoption of truly portable, smart devices and Do-It-Yourself computing platforms by the general public has enabled the rise of new network and system paradigms. This abundance of wellconnected, well-equipped, affordable devices, when combined with crowdsourcing methods, enables the development of systems with the aid of the crowd. In this work, we introduce the paradigm of Crowdsourced Systems, systems whose constituent infrastructure, or a significant part of it, is pooled from the general public by following crowdsourcing methodologies. We discuss the particular distinctive characteristics they carry and also provide their “canonical” architecture. We exemplify the paradigm by also introducing Crowdcloud, a crowdsourced cloud infrastructure where crowd members can act both as cloud service providers and cloud service clients. We discuss its characteristic properties and also provide its functional architecture. The concepts introduced in this work underpin recent advances in the areas of mobile edge/fog computing and co-designed/cocreated systems

A Vaccine against Nicotine for Smoking Cessation: A Randomized Controlled Trial

BACKGROUND: Tobacco dependence is the leading cause of preventable death and disabilities worldwide and nicotine is the main substance responsible for the addiction to tobacco. A vaccine against nicotine was tested in a 6-month randomized, double blind phase II smoking cessation study in 341 smokers with a subsequent 6-month follow-up period. METHODOLOGY/PRINCIPAL FINDINGS: 229 subjects were randomized to receive five intramuscular injections of the nicotine vaccine and 112 to receive placebo at monthly intervals. All subjects received individual behavioral smoking cessation counseling. The vaccine was safe, generally well tolerated and highly immunogenic, inducing a 100% antibody responder rate after the first injection. Point prevalence of abstinence at month 2 showed a statistically significant difference between subjects treated with Nicotine-Qbeta (47.2%) and placebo (35.1%) (P = 0.036), but continuous abstinence between months 2 and 6 was not significantly different. However, in subgroup analysis of the per-protocol population, the third of subjects with highest antibody levels showed higher continuous abstinence from month 2 until month 6 (56.6%) than placebo treated participants (31.3%) (OR 2.9; P = 0.004) while medium and low antibody levels did not increase abstinence rates. After 12 month, the difference in continuous abstinence rate between subjects on placebo and those with high antibody response was maintained (difference 20.2%, P = 0.012). CONCLUSIONS: Whereas Nicotine-Qbeta did not significantly increase continuous abstinence rates in the intention-to-treat population, subgroup analyses of the per-protocol population suggest that such a vaccination against nicotine can significantly increase continuous abstinence rates in smokers when sufficiently high antibody levels are achieved. Immunotherapy might open a new avenue to the treatment of nicotine addiction. TRIAL REGISTRATION: Swiss Medical Registry 2003DR2327; ClinicalTrials.gov NCT00369616

Vaccination with nanoparticles combined with micro-adjuvants protects against cancer.

Induction of strong T cell responses, in particular cytotoxic T cells, is a key for the generation of efficacious therapeutic cancer vaccines which yet, remains a major challenge for the vaccine developing world. Here we demonstrate that it is possible to harness the physiological properties of the lymphatic system to optimize the induction of a protective T cell response. Indeed, the lymphatic system sharply distinguishes between nanoscale and microscale particles. The former reaches the fenestrated lymphatic system via diffusion, while the latter either need to be transported by dendritic cells or form a local depot. Our previously developed cucumber-mosaic virus-derived nanoparticles termed (CuMV <sub>TT</sub> -VLPs) incorporating a universal Tetanus toxoid epitope TT830-843 were assessed for their draining kinetics using stereomicroscopic imaging. A nano-vaccine has been generated by coupling p33 epitope as a model antigen to CuMV <sub>TT</sub> -VLPs using bio-orthogonal Cu-free click chemistry. The CuMV <sub>TT</sub> -p33 nano-sized vaccine has been next formulated with the micron-sized microcrystalline tyrosine (MCT) adjuvant and the formed depot effect was studied using confocal microscopy and trafficking experiments. The immunogenicity of the nanoparticles combined with the micron-sized adjuvant was next assessed in an aggressive transplanted murine melanoma model. The obtained results were compared to other commonly used adjuvants such as B type CpGs and Alum. Our results showed that CuMV <sub>TT</sub> -VLPs can efficiently and rapidly drain into the lymphatic system due to their nano-size of ~ 30 nm. However, formulating the nanoparticles with the micron-sized MCT adjuvant of ~ 5 μM resulted in a local depot for the nanoparticles and a longer exposure time for the immune system. The preclinical nano-vaccine CuMV <sub>TT</sub> -p33 formulated with the micron-sized MCT adjuvant has enhanced the specific T cell response in the stringent B16F10p33 murine melanoma model. Furthermore, the micron-sized MCT adjuvant was as potent as B type CpGs and clearly superior to the commonly used Alum adjuvant when total CD8 <sup>+</sup> , specific p33 T cell response or tumour protection were assessed. The combination of nano- and micro-particles may optimally harness the physiological properties of the lymphatic system. Since the nanoparticles are well defined virus-like particles and the micron-sized adjuvant MCT has been used for decades in allergen-specific desensitization, this approach may readily be translated to the clinic

Fibroblast cell-based therapy prevents induction of alopecia areata in an experimental model

YesAlopecia areata (AA) is an autoimmune hair loss disease with infiltration of proinflammatory cells into hair follicles. Current therapeutic regimens are unsatisfactory mainly because of the potential for side effects and/or limited efficacy. Here we report that cultured, transduced fibroblasts, which express the immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO), can be applied to prevent hair loss in an experimental AA model. A single intraperitoneal (IP) injection of IDO-expressing primary dermal fibroblasts was given to C3H/HeJ mice at the time of AA induction. While 60–70% of mice that received either control fibroblasts or vehicle injections developed extensive AA, none of the IDO-expressing fibroblast-treated mice showed new hair loss up to 20 weeks post injection. IDO cell therapy significantly reduced infiltration of CD4+ and CD8+ T cells into hair follicles and resulted in decreased expression of TNF-α, IFN-γ and IL-17 in the skin. Skin draining lymph nodes of IDO fibroblast-treated mice were significantly smaller, with more CD4+ CD25+ FoxP3+ regulatory T cells and fewer Th17 cells than those of control fibroblast and vehicle-injected mice. These findings indicate that IP injected IDO-expressing dermal fibroblasts can control inflammation and thereby prevent AA hair loss.Canadian Institutes of Health Researches (Funding Reference Number: 134214 and 136945)

The Transformation of Arenes into Acetyl Dienes via Nucleophilic Addition to Arene-Cr(CO)>3> Complexes and Trapping with Mel

Anionic cyclohexadienyl–Cr(CO)3 complexes, formed by addition of reactive carbanions to benzene–Cr(CO)3 and naphthalene–Cr(CO)3 complexes, react with Mel by addition and carbonylation to yield disubstituted cyclohexadienes and dihydronaphthalenes, respectively