Designed spiro-bicyclic analogues targeting the ribosomal decoding center

The bacterial ribosome represents the confirmed biological target for many known antibiotics that interfere with bacterial protein synthesis. Aminoglycosides represent a lead paradigm in RNA molecular recognition and constitute ideal starting points for the design and synthesis of novel RNA binders. Previous rational design approaches of RNA-targeting small molecules have been mainly concentrated on direct functionalization of aminoglycosidic substructures. Herein, we successfully designed and synthesized rigid spirocyclic scaffolds locked in a predicted ribosome-bound "bioactive" conformation. These analogues are able to mimic many of the interactions of the natural products for the A-site, as proven by their obtained binding affinities. The development of an optimized approach for their synthesis and their potential to inhibit protein production in vitro are presented. Our results could be further utilized for the development of analogues with improved antibiotic profiles.     

Ezetimibe Treatment Lowers Indicators of Oxidative Stress in Hypercholesterolemic Subjects with High Oxidative Stress

Ezetimibe effectively reduces low-density lipoprotein cholesterol (LDL-C). In this study, we tested the hypothesis that ezetimibe monotherapy may also decrease markers of oxidative stress in subjects with hypercholesterolemia. Subjects with hypercholesterolemia and no evidence of cardiovascular disease were randomly allocated to open-label ezetimibe monotherapy 10 mg/day (EZT group) or therapeutic lifestyle changes (TLC group). At baseline and 12 weeks post-treatment serum lipoprotein and apolipoprotein levels as well as oxidative stress parameters, including oxidized LDL (ox-LDL), 8-isoprostanes (8-epiPGF2a) and reactive oxygen metabolites (d-ROMs) levels, were blindly determined. A total of 60 patients were included; 30 in each group. Despite a significant decrease in ox-LDL levels (by 20.8%, p < 0.001 vs. baseline; p < 0.001 vs. TLC group) in the EZT group no change in the ratio ox-LDL to LDL-C was noticed following ezetimibe treatment. No significant change in 8-epiPGF2a and d-ROMs levels was observed in the EZT group. Of note, a significant decrease in 8-epiPGF2a and d-ROMs levels (by 20.4% and 18.2%, respectively, p < 0.01 vs. baseline for both), was noted among patients in the EZT group who exhibited ‘high oxidative stress’ at baseline. No change in any of oxidative stress parameters was noted in the TLC group. Ezetimibe may decrease markers of oxidative stress in hypercholesterolemic subjects. This benefit may be more profound among patients who exhibit ‘high oxidative stress’ at baseline.     

发展小型清洁发展机制可再生能源项目的简化程序

各种灵活的京都机制已经作为以市场为基础的解决气候变化的方法发展起来了。更具体的说，清洁发展机制(CDM)是指一个工业化国家通过在发展中国家实施减排项目(特别是可再生能源项目)来实现其部分减排义务的一种灵活机制。目前发展中国家没有承担减少温室气体排放方面的义务。介绍了京都议定书的清洁发展机制促进可再生能源(RES)投资的能力，并且分析了在CDM机制下小型项目的发展潜力。     

Electrochemical enhancement of solar photocatalysis: degradation of endocrine disruptor bisphenol-A on Ti/TiO2 films

The photoelectrocatalytic oxidation over immobilized Ti/TiO₂ films in the presence of simulated solar light was investigated for the degradation of bisphenol-A (BPA) in water. The catalyst, consisting of 75:25 anatase:rutile, was prepared by a sol-gel method and characterized by cyclic voltammetry, X-ray diffraction and scanning electron microscopy. Experiments were conducted to assess the effect of applied current (0.02-0.32 mA/cm²), TiO₂ loading (1.3-9.2 mg), BPA concentration (120-820 μg/L), initial solution pH (1 and 7.5) and the aqueous matrix (pure water and treated effluent) on BPA photoelectrocatalytic degradation which was monitored by high performance liquid chromatography equipped with a fluorescence detector. The reaction was favored at anodic currents up to 0.04 mA/cm² and lower substrate concentrations, but it was hindered by the presence of residual organic matter and radical scavengers (e.g. bicarbonates) in treated effluents. Moreover, a pseudo-first order kinetic model could fit the experimental data well with the apparent reaction constant taking values between 2.9 and 32.4 10⁻³/min. The degradation of BPA by pure photocatalysis or electrochemical oxidation alone was also studied leading to partial substrate removal. In all cases, the contribution of applied potential to photocatalytic degradation was synergistic with the photocatalytic efficiency increasing between 24% and 97% possibly due to a more efficient separation and utilization of the photogenerated charge carriers. The effect of photoelectrocatalysis on the ecotoxic and estrogenic properties of BPA was also evaluated measuring the bioluminescence inhibition of Vibrio fischeri and performing the yeast estrogen screening assay, respectively.     

Formation of furan in baby food products: Identification and technical challenges

Furan is generally produced during thermal processing of various foods including baked, fried, and roasted food items such as cereal products, coffee, canned, and jarred prepared foods as well as in baby foods. Furan is a toxic and carcinogenic compound to humans and may be a vital hazard to infants and babies. Furan could be formed in foods through thermal degradation of carbohydrates, dissociation of amino acids, and oxidation of polyunsaturated fatty acids. The detection of furan in food products is difficult due to its high volatility and low molecular weight. Headspace solid-phase microextraction coupled with gas chromatography/mass spectrometer (GC/MS) is generally used for analysis of furan in food samples. The risk assessment of furan can be characterized using margin of exposure approach (MOE). Conventional strategies including cooking in open vessels, reheating of commercially processed foods with stirring, and physical removal using vacuum treatment have remained unsuccessful for the removal of furan due to the complex production mechanisms and possible precursors of furan. The innovative food-processing technologies such as high-pressure processing (HPP), high-pressure thermal sterilization (HPTS), and Ohmic heating have been adapted for the reduction of furan levels in baby foods. But in recent years, only HPP has gained interest due to successful reduction of furan because of its nonthermal mechanism. HPP-treated baby food products are commercially available from different food companies. This review summarizes the mechanism involved in the formation of furan in foods, its toxicity, and identification in infant foods and presents a solution for limiting its formation, occurrence, and retention using novel strategies.     

High-level customization framework for application-specific NoC architectures

Network-on-Chip (NoC) has been recognized as the new paradigm to interconnect and organize a high number of cores. NoCs address global communication issues in System-on-Chips (SoC) involving communication-centric design and implementation of scalable communication structures evolving application-specific NoC design as a key challenge to modern SoC design. In this paper we present a SystemC customization framework and methodology for automatic design and evaluation of regular and irregular NoC architectures. The presented framework also supports application-specific optimization techniques such as priority assignment, node clustering and buffer sizing. Experimental results show that generated regular NoC architectures achieve an average of 5.5 % lower communication-cost compared to other regular NoC designs while irregular NoCs proved to achieve on average 4.5×higher throughput and 40 % network delay reduction compared to regular mesh topologies. In addition, employing a buffer sizing algorithm we achieve a reduction in network’s power consumption by an average of 45 % for both regular and irregular NoC design flow.     

UDS: A Distributed RAT Selection Mechanism for Heterogeneous Wireless Networks

The selection of the most suitable radio access technology to serve as the communication means for a service in a heterogeneous wireless access network is a complex task. It considers a number of different parameters and it involves numerous network technologies and entities. Several mechanisms have been proposed that focus on different aspects and follow different strategies. We introduce a policy based scheme that takes into consideration the user preferences, along with network conditions and user moving speed. Its ultimate goal is to support a session through the most desirable radio access technology, from the user perspective, while managing the overall network resources in an optimum way. It comprises a distributed algorithm running at the terminal and the network side. The performance of the proposed mechanism is evaluated against that of a typical load balancing scheme, commonly used in the literature. The results show that the holistic treatment of the diverse parameters fulfils the aforementioned goal.     

Integrating the self‐growing concept in a self‐organizing wireless network for topology optimization

The concept of self‐organizing networks is considered one of the most promising approaches for the efficient management of future wireless networks that will support a large number of nodes and a plethora of services with diverse characteristics. Today, different types of networks (e.g. WLANs, wireless sensor networks) are deployed to serve different needs but do not interoperate. Their possible loose integration will provide opportunities that could be exploited through collaborative approaches to devise novel solutions to extend the capabilities and improve the performance of these networks. The self‐growing paradigm addresses this challenge by extending network nodes to dynamically evolve in terms of purpose and operational features. In this paper we describe the CONSERN architecture, which targets the realization of the self‐growing concept in the context of self‐organized networks. To test our ideas we designed and implemented a WLAN topology optimization scheme that provides the best coverage at a minimum energy consumption, through dynamic access point (AP) deactivation and reactivation. Using self‐growing mechanisms and typical motion detectors we present how the operation of the proposed topology optimization mechanism can be improved. The reduced energy consumption attained under the proposed scheme at the AP side, as well as the efficient utilization of network resources, are evaluated via a proof‐of‐concept implementation that we have deployed in a real office environment that consists of WLAN APs and motion sensors. Copyright © 2014 John Wiley & Sons, Ltd.