Fractal Nanotechnology

Self-similar patterns are frequently observed in Nature. Their reproduction is possible on a length scale 102–105 nm with lithographic methods, but seems impossible on the nanometer length scale. It is shown that this goal may be achieved via a multiplicative variant of the multi-spacer patterning technology, in this way permitting the controlled preparation of fractal surfaces

automotive turbochargers power estimation based on speed fluctuation analysis

Turbocharging technology will play a crucial role in the near future as a way to meet the requirements for pollutant emissions and fuel consumption reduction. However, optimal turbocharger control is still an issue, especially for downsized engines fitted with a low number of cylinders. As a matter of fact, automotive turbochargers are characterized by wide operating range and unsteady gas flow through the turbine, while only steady flow maps are usually provided by the manufacturer. In addition, in passenger cars applications, real-time turbocharger optimal control is even more difficult because of the lack of information about pressure/temperature in turbine upstream/downstream circuits and turbocharger rotational speed. In order to overcome these unknowns, this work presents a methodology for instantaneous turbocharger rotational speed determination through a proper processing of the signal coming from one accelerometer mounted on the compressor diffuser, or one microphone facing the compressor. The presented approach can be used to evaluate both turbocharger speed mean value and the amplitude of turbocharger speed fluctuations caused by the pulsating gas flow in turbine upstream and downstream circuits. Once turbocharger speed has been determined, it can be used to estimate power delivered by the turbine. The whole estimation algorithm has been developed and validated for a light duty turbocharged Common-Rail Diesel engine mounted in a test cell. However, the developed methodology is general and can be applied to different turbochargers, both for Spark Ignited and Diesel applications. © 2015 Published by Elsevier Ltd

Integrative Approaches in Structural Biology: A More Complete Picture from the Combination of Individual Techniques

With the recent technological and computational advancements, structural biology has begun to tackle more and more difficult questions, including complex biochemical pathways and transient interactions among macromolecules. This has demonstrated that, to approach the complexity of biology, one single technique is largely insufficient and unable to yield thorough answers, whereas integrated approaches have been more and more adopted with successful results. Traditional structural techniques (X-ray crystallography and Nuclear Magnetic Resonance (NMR)) and the emerging ones (cryo-electron microscopy (cryo-EM), Small Angle X-ray Scattering (SAXS)), together with molecular modeling, have pros and cons which very nicely complement one another. In this review, three examples of synergistic approaches chosen from our previous research will be revisited. The first shows how the joint use of both solution and solid-state NMR (SSNMR), X-ray crystallography, and cryo-EM is crucial to elucidate the structure of polyethylene glycol (PEG)ylated asparaginase, which would not be obtainable through any of the techniques taken alone. The second deals with the integrated use of NMR, X-ray crystallography, and SAXS in order to elucidate the catalytic mechanism of an enzyme that is based on the flexibility of the enzyme itself. The third one shows how it is possible to put together experimental data from X-ray crystallography and NMR restraints in order to refine a protein model in order to obtain a structure which simultaneously satisfies both experimental datasets and is therefore closer to the ‘real structure’.Microbial Biotechnolog

Critical Review of Theoretical Models for Anomalous Effects (Cold Fusion) in Deuterated Metals

We briefly summarize the reported anomalous effects in deuterated metals at ambient temperature, commonly known as "Cold Fusion" (CF), with an emphasis on important experiments as well as the theoretical basis for the opposition to interpreting them as cold fusion. Then we critically examine more than 25 theoretical models for CF, including unusual nuclear and exotic chemical hypotheses. We conclude that they do not explain the data.Comment: 51 pages, 4 Figure

A Structurally Simple Vaccine Candidate Reduces Progression and Dissemination of Triple-Negative Breast Cancer

The Tn antigen is a well-known tumor-associated carbohydrate determinant, often incorporated in glycopeptides to develop cancer vaccines. Herein, four copies of a conformationally constrained mimetic of the antigen TnThr (GalNAc-Thr) were conjugated to the adjuvant CRM197, a protein licensed for human use. The resulting vaccine candidate, mime[4]CRM elicited a robust immune response in a triple-negative breast cancer mouse model, correlated with high frequency of CD4+ T cells and low frequency of M2-type macrophages, which reduces tumor progression and lung metastasis growth. Mime[4]CRM-mediated activation of human dendritic cells is reported, and the proliferation of mime[4]CRM-specific T cells, in cancer tissue and peripheral blood of patients with breast cancer, is demonstrated. The locked conformation of the TnThr mimetic and a proper presentation on the surface of CRM197 may explain the binding of the conjugate to the anti-Tn antibody Tn218 and its efficacy to fight cancer cells in mice

Endo-therapies for biliary duct-to-duct anastomotic stricture after liver transplantation: outcomes of a nationwide survey

BACKGROUND: The most appropriate endo-therapeutic approach to biliary anastomotic strictures is yet to be defined. AIM: To retrospectively report on the endo-therapy of duct-to-duct anastomotic strictures during 2013 in Italy. METHODS: Data were collected from 16 Endoscopy Units at the Italian Liver Transplantation Centers (BASALT study group). RESULTS: Complete endo-therapy and follow-up data are available for 181 patients: 101 treated with plastic multistenting, 26 with fully covered self-expandable metal stenting (SEMS) and 54 with single stenting. Radiological success was achieved for 145 patients (80%), i.e. 88% of plastic multistenting, 88% of SEMS and 61% of single stenting (p<0.001 vs plastic multistenting; p<0.05 vs SEMS)]. After first-line endo-therapy failure, the patients underwent a second-line endo-therapy with plastic multistenting for 25%, fully covered SEMS for 53% and single stenting for 22% of cases, and radiological success was achieved for 84%, i.e. 100%, 85%, and 63% with plastic multistenting, SEMS and single stenting (p<0.05 vs plastic multistenting or SEMS), respectively. Procedure-related complications occurred in 7.8% of ERCP. Overall clinical success was achieved in 87% of patients after a median follow-up of 25 months. CONCLUSION: Plastic multistenting is confirmed as the preferred first-line treatment, while fully covered SEMS as rescue option for biliary anastomotic strictures. Single stenting has sub-optimal results and should be abandoned. This article is protected by copyright. All rights reserved

Regulation of HuR structure and function by dihydrotanshinone-I

The Human antigen R protein (HuR) is an RNA-binding protein that recognizes U/AU-rich elements in diverse RNAs through two RNA-recognition motifs, RRM1 and RRM2, and post-transcriptionally regulates the fate of target RNAs. The natural product dihydrotanshinone-I (DHTS) prevents the association of HuR and target RNAs in vitro and in cultured cells by interfering with the binding of HuR to RNA. Here, we report the structural determinants of the interaction between DHTS and HuR and the impact of DHTS on HuR binding to target mRNAs transcriptome-wide. NMR titration and Molecular Dynamics simulation identified the residues within RRM1 and RRM2 responsible for the interaction between DHTS and HuR. RNA Electromobility Shifts and Alpha Screen Assays showed that DHTS interacts with HuR through the same binding regions as target RNAs, stabilizing HuR in a locked conformation that hampers RNA binding competitively. HuR ribonucleoprotein immunoprecipitation followed by microarray (RIP-chip) analysis showed that DHTS treatment of HeLa cells paradoxically enriched HuR binding to mRNAs with longer 3'UTR and with higher density of U/AU-rich elements, suggesting that DHTS inhibits the association of HuR to weaker target mRNAs. In vivo, DHTS potently inhibited xenograft tumor growth in a HuR-dependent model without systemic toxicity

Mixing Aβ(1-40) and Aβ(1-42) peptides generates unique amyloid fibrils

Recent structural studies show distinct morphologies for the fibrilsof Ab(1-42) and Ab(1-40), which are believed not to co-fibrillize.We describe here a novel, structurally-uniform 1 : 1 mixed fibrillarspecies, which differs from bothpure fibrils. It forms preferen-tially even when Ab(1-42) : Ab(1-40) peptides are mixed in a non-stoichiometric ratio