Camptothecin‐7‐yl‐methanthiole: Semisynthesis and Biological Evaluation

The introduction of a methylenthiol group at position 7 of camptothecin was carried out in four steps. This preparation also yielded the corresponding disulfide, which behaves as a prodrug due to its reactivity with glutathione. Assessment of their antiproliferative activities, investigations of their mechanism of action, and molecular modeling analysis indicated that the 7‐modified camptothecin derivatives described herein maintain the biological activity and drug–target interactions of the parent compound.     

Early Nascent Chain Folding Events on the Ribosome

To maintain optimal protein homeostasis within the cell, a complex interplay exists between factors determining the production, transport, and folding of nascent chains. Here we review the evidence for the structural and dynamical properties of nascent polypeptide chains as they emerge from the ribosome and that enable them to acquire their biologically active, three-dimensional structures. In particular, we focus on the application of NMR spectroscopy, which is now emerging as a powerful technique to probe the behavior and properties of emerging nascent chains.     

Policy plan for the use of biomass and biofuels in Greece: Part I: Available biomass and methodology

Greece is a country in which biomass can play an important role in achieving the 2010 national target of 20% electricity production from Renewable Energy Sources (RES) Residues from traditional agricultural activities, but also the cultivation of new energy crops, can lead to a high level of availability and utilization of biomass energy products in Greece. In order for biomass to make a substantial contribution to the 2010 national target, set by the EU RES Directive 2001/77, as well as the corresponding 2020 target, to be set by the upcoming RES Framework Directive, a national policy plan for biomass and biofuels has to be formulated. This plan will assess the available biomass quantities and the potential and routes, by which this biomass can be converted to final energy products. The aim of the present paper is to discuss the current situation and prospects of biomass availability and exploitation in Greece and to develop a coherent and reliable methodology, in order to assess the conversion of the country’ s biomass potential into useful energy products.     

Measurement of the electromagnetic field radiating by commercial ESD generators with the Pellegrini target on insulating material

The aim of this work is the investigation of the transient electromagnetic field radiating by two different commercial generators of electrostatic discharges. Measurements of both magnetic and electric field generated by contact electrostatic discharges have been carried out a few centimeters away from the discharge point. In this paper the current transducer, which is used for the measurement of the discharge current is not mounted on a grounded metal plate, but on an insulating material. With this aberration to the Standard a closer simulation to the electromagnetic field produced by the electrostatic discharge generators on the equipment under test is obtained. This experiment is closer to real conditions of electrostatic discharges, which do not involve a metal plate. It is proved by measurements that each generator produces a different transient electromagnetic field, which has different repercussions on the equipment that is tested. Comparisons of the radiating field between the two generators and useful conclusions for the variation of the electromagnetic field are also presented.     

A new approach to the design of amperometric gas sensors

Preliminary experiments are described in order to demonstrate the principle of a new design of amperometric gas sensors. In this design, non-porous electrodes are all fabricated onto the gas side of a proton conducting medium so that the oxidation/reduction of the gas to be sensed occurs at the three phase interface between the atmosphere, the electrode and the proton conducting medium, i.e. the system approximates to a line electrode. Such a cell is described which gives good quality responses for the oxidation of SO₂ from the gas phase.     

Lactobacillus fermentum ACA-DC 179 displays probiotic potential in vitro and protects against trinitrobenzene sulfonic acid (TNBS)-induced colitis and Salmonella infection in murine models

Lactobacillus fermentum ACA-DC 179, Lactobacillus plantarum ACA-DC 287 and Streptococcus macedonicus ACA-DC 198 were studied for their probiotic potential. Firstly, strains were screened for antimicrobial activity towards a broad range of target strains, including lactic acid bacteria, food spoilage and pathogenic bacteria. L. fermentum ACA-DC 179 was active against five streptococci, including the two pathogenic strains Streptococcus oralis LMG 14532T and Streptococcus pneumoniae LMG 14545T. S. macedonicus ACA-DC 198 was active against the majority of the strains tested, including not only lactic acid bacteria but also many food spoilage or pathogenic species. The three potential probiotic strains were found to survive variably at pH 2.5 and were unaffected by bile salts. Only S. macedonicus ACA-DC 198 exhibited bile salt hydrolase activity, while none of the strains was haemolytic. Moreover, strains exhibited variable susceptibility towards commonly used antibiotics. L. plantarum ACA-DC 287 and S. macedonicus ACA-DC 198 induced the secretion of the pro-inflammatory cytokines IL-12, IFN-gamma and TNF-alpha by human peripheral blood mononuclear cells. Also elevated levels of the anti-inflammatory IL-10 were observed with L. fermentum ACA-DC 179. This strain consequently was found to significantly reduce colitis in a TNBS-induced colitis mouse model. Furthermore, L. fermentum ACA-DC 179 was successfully applied in an experimental Salmonella-infection mouse model. To conclude, strain L. fermentum ACA-DC 179 possesses desirable probiotic properties, such as antimicrobial activity and immunomodulation in vitro, which were confirmed in vivo by the use of animal models.     

EEG transient event detection and classification using association rules.

In this paper, a methodology for the automated detection and classification of transient events in electroencephalographic (EEG) recordings is presented. It is based on association rule mining and classifies transient events into four categories: epileptic spikes, muscle activity, eye blinking activity, and sharp alpha activity. The methodology involves four stages: 1) transient event detection; 2) clustering of transient events and feature extraction; 3) feature discretization and feature subset selection; and 4) association rule mining and classification of transient events. The methodology is evaluated using 25 EEG recordings, and the best obtained accuracy was 87.38%. The proposed approach combines high accuracy with the ability to provide interpretation for the decisions made, since it is based on a set of association rules.     

Structural model updating and prediction variability using Pareto optimal models

A multi-objective identification method for structural model updating based on modal residuals is presented. The method results in multiple Pareto optimal structural models that are consistent with the experimentally measured modal data and the modal residuals used to measure the discrepancies between the measured and model predicted modal characteristics. These Pareto optimal models are due to uncertainties arising from model and measurement errors. The relation between the multi-objective identification method and the conventional single-objective weighted modal residuals method for model updating is investigated. Using this relation, an optimally weighted modal residuals method is also proposed to rationally select the most preferred model among the alternative multiple Pareto optimal models for further use in structural model prediction studies. Computational issues related to the reliable solution of the resulting multi-objective and single optimization problems are addressed. The model updating methods are compared and their effectiveness is demonstrated using experimental results obtained from a three-story laboratory structure tested at a reference and a mass modified configuration. The variability of the Pareto optimal models and their associated response prediction variability are explored using two structural model classes, a simple 3-DOF model class and a higher fidelity 546-DOF finite element model class. It is demonstrated that the Pareto optimal structural models and the corresponding response and reliability predictions may vary considerably, depending on the fidelity of the model class and the size of measurement errors.     

Improving the Price of Anarchy for Selfish Routing via Coordination Mechanisms

We reconsider the well-studied Selfish Routing game with affine latency functions. The Price of Anarchy for this class of games takes maximum value 4/3; this maximum is attained already for a simple network of two parallel links, known as Pigou’s network. We improve upon the value 4/3 by means of Coordination Mechanisms. We increase the latency functions of the edges in the network, i.e., if ? _e (x) is the latency function of an edge e, we replace it by $\hat{\ell}_{e}(x)$ with $\ell_{e}(x) \le \hat{\ell}_{e}(x)$ for all x. Then an adversary fixes a demand rate as input. The engineered Price of Anarchy of the mechanism is defined as the worst-case ratio of the Nash social cost in the modified network over the optimal social cost in the original network. Formally, if $\hat{C}_{N} (r)$ denotes the cost of the worst Nash flow in the modified network for rate r and C _opt (r) denotes the cost of the optimal flow in the original network for the same rate then $$\mathit{ePoA} = \max_{r \ge 0} \frac{\hat{C}_N(r)}{C_{\mathit{opt}}(r)}. $$ We first exhibit a simple coordination mechanism that achieves for any network of parallel links an engineered Price of Anarchy strictly less than 4/3. For the case of two parallel links our basic mechanism gives 5/4=1.25. Then, for the case of two parallel links, we describe an optimal mechanism; its engineered Price of Anarchy lies between 1.191 and 1.192.     

The importance of loop length in the folding of an immunoglobulin domain

Immunoglobulin (Ig)-like proteins have been shown to fold following formation of a nucleus comprising interactions between residues that are distant in the primary sequence. What role do the loops connecting these nucleus residues play? Here, the importance of loops connecting beta-strands in different sheets of the Ig fold is investigated, by insertion of five glycine residues into the B-C loop of an Ig domain from human titin, TI I27. The folding pathway of this elongated 'pseudo wild-type' TI I27 is probed using protein engineering and Phi-value analysis. The Phi-values calculated for mutants within the pseudo wild-type protein indicate that the folding nucleus in wild-type TI I27 is conserved, supporting the hypothesis that the inter-sheet loop is not critical to the formation of a long-range folding nucleus.