Optimization of piers for retaining walls

The ultimate strength design of reinforced concrete members under flexure and axial loads is well known, with solutions dating back to the 1950s. There is little motivation for engineers to change solution approaches in the absence of a clear benefit, particularly given that current solution approaches are well-known and do not raise controversy. Recently, a different solution approach has been presented in the form of Reinforcement Sizing Diagrams and Optimal Domains, but applications to rectangular sections were limited and thus the approach has been mainly of academic or theoretical interest. This paper presents an application to circular sections, which allow the advantages to be realized in the commonly encountered situation of retaining walls supported by circular section piers. Using the approach presented herein, longitudinal reinforcement can be reduced up to 50% compared with traditional designs, allowing significant financial savings while also reducing the greenhouse gas emissions associated with the reinforcement component of reinforced concrete construction.     

Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.     

Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens

Outer Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a tool for linking antigens, also from phylogenetically distant pathogens, to OMV. Here we develop two simple and widely applicable conjugation chemistries targeting proteins or lipopolysaccharides on the surface of Generalized Modules for Membrane Antigens (GMMA), OMV spontaneously released from Gram-negative bacteria mutated to increase vesicle yield and reduce potential reactogenicity. A Design of Experiment approach was used to identify optimal conditions for GMMA activation before conjugation, resulting in consistent processes and ensuring conjugation efficiency. Conjugates produced by both chemistries induced strong humoral response against the heterologous antigen and GMMA. Additionally, the use of the two orthogonal chemistries allowed to control the linkage of two different antigens on the same GMMA particle. This work supports the further advancement of this novel platform with great potential for the design of effective vaccines.     

Dihydroartemisinin–Bile Acid Hybridization as an Effective Approach to Enhance Dihydroartemisinin Anticancer Activity

A series of hybrid compounds based on natural products—bile acids and dihydroartemisinin—were prepared by different synthetic methodologies and investigated for their in vitro biological activity against HL-60 leukemia and HepG2 hepatocellular carcinoma cell lines. Most of these hybrids presented significantly improved antiproliferative activities with respect to dihydroartemisinin and the parent bile acid. The two most potent hybrids of the series exhibited a 10.5- and 15.4-fold increase in cytotoxic activity respect to dihydroartemisinin alone in HL-60 and HepG2 cells, respectively. Strong evidence that an ursodeoxycholic acid hybrid induced apoptosis was obtained by flow cytometric analysis and western blot analysis.     

Identification of two glutamic acid residues essential for catalysis in the {beta}-glycosidase from the thermoacidophilic archaeon Sulfolobus solfataricus

The Sulfolobus solfataricus, strain MT4, ß-glycosidase(Ssßgly) is a thermophilic member of glycohydrolasefamily 1. To identify active-site residues, glutamic acids 206and 387 have been changed to isosteric glutamine by site-directedmutagenesis. Mutant proteins have been purified to homogeneityusing the Schistosoma japonicum glutathione S-transferase (GST)fusion system. The proteolytic cleavage of the chimeric proteinwith thrombin was only obtainable after the introduction ofa molecular spacer between the GST and the Ssß-glydomains. The Glu387 Gin mutant showed no detectable activity,as expected for the residue acting as the nucleophile of thereaction. The Glu206 Gin mutant showed 10- and 60-fold reducedactivities on aryl-galacto and aryl-glucosides, respectively,when compared with the wild type. Moreover, a significant K_mdecrease with plo-nitrophenyl-ß-D-glucoside was observed.The residual activity of the Glu206 Gln mutant lost the typicalpH dependence shown by the wild type. These data suggest thatGlu206 acts as the general acid/base catalyst in the hydrolysisreaction.     

Commercial Supported Gold Nanoparticles Catalyzed Alkyne Hydroamination and Indole Synthesis

Commercial gold nanoparticles supported on titanium dioxide (TiO₂) were found to be a highly efficient catalyst for alkyne hydroamination. Terminal alkynes could easily undergo intermolecular hydroamination with low catalyst loadings (0.2 mol% Au) under solvent‐free conditions. Indoles were efficiently synthesized using microwave heating through intramolecular hydroamination.

     

Targeting Serotonin 2A and Adrenergic α1 Receptors for Ocular Antihypertensive Agents: Discovery of 3,4‐Dihydropyrazino[1,2‐b]indazol‐1(2H)‐one Derivatives

Glaucoma affects millions of people worldwide and causes optic nerve damage and blindness. The elevation of the intraocular pressure (IOP) is the main risk factor associated with this pathology, and decreasing IOP is the key therapeutic target of current pharmacological treatments. As potential ocular hypotensive agents, we studied compounds that act on two receptors (serotonin 2A and adrenergic α₁) linked to the regulation of aqueous humour dynamics. Herein we describe the design, synthesis, and pharmacological profiling of a series of novel bicyclic and tricyclic N2‐alkyl‐indazole‐amide derivatives. This study identified a 3,4‐dihydropyrazino[1,2‐b]indazol‐1(2H)‐one derivative with potent serotonin 2A receptor antagonism, >100‐fold selectivity over other serotonin subtype receptors, and high affinity for the α₁ receptor. Moreover, upon local administration, this compound showed superior ocular hypotensive action in vivo relative to the clinically used reference compound timolol.     

A log square average case algorithm to make insertions in fast similarity search

To speed up similarity based searches many indexing techniques have been proposed in order to address the problem of efficiency. However, most of the proposed techniques do not admit fast insertion of new elements once the index is built. The main effect is that changes in the environment are very costly to be taken into account.In this work, we propose a new technique to allow fast insertions of elements in a family of static tree-based indexes. Unlike other techniques, the resulting index is exactly equal to the index that would be obtained by building it from scratch. Therefore there is no performance degradation in search time.We show that the expected number of distance computations (and the average time complexity) is bounded by a function that grows with log²(n) where n is the size of the database.In order to check the correctness of our approach some experiments with artificial and real data are carried out.     

Industrial Requirements for Distributed SCM Tool

As software development comes to be viewed more and more as an engineering discipline, Software Configuration Management is increasingly recognised as a key technology in the development of software. The Esprit VISCOUNT project¹ aim is to implement an innovative Software Configuration Management (SCM) tool to use in a geographically distributed software development environment, a Virtual Software Corporation (VSC). The features implemented by the tool will be the following: ·Configurable process modelling ·Inter-working capabilities with COTS SCM tools ·Selective replication of archives ·Open to include plug-in applications (security mechanism, encryption, etc) This paper is based on the work undertaken as part of the VISCOUNT project, partially funded by European Union's Esprit Programme, and it describes the SIA (Societa' Italiana Avionica) requirements defined in the framework of VISCOUNT. This revised version was published online in August 2006 with corrections to the Cover Date.     

Music staff removal with supervised pixel classification

This work presents a novel approach to tackle the music staff removal. This task is devoted to removing the staff lines from an image of a music score while maintaining the symbol information. It represents a key step in the performance of most optical music recognition systems. In the literature, staff removal is usually solved by means of image processing procedures based on the intrinsics of music scores. However, we propose to model the problem as a supervised learning classification task. Surprisingly, although there is a strong background and a vast amount of research concerning machine learning, the classification approach has remained unexplored for this purpose. In this context, each foreground pixel is labelled as either staff or symbol. We use pairs of scores with and without staff lines to train classification algorithms. We test our proposal with several well-known classification techniques. Moreover, in our experiments no attempt of tuning the classification algorithms has been made, but the parameters were set to the default setting provided by the classification software libraries. The aim of this choice is to show that, even with this straightforward procedure, results are competitive with state-of-the-art algorithms. In addition, we also discuss several advantages of this approach for which conventional methods are not applicable such as its high adaptability to any type of music score.