With digital equipment becoming increasingly networked, either on wired or wireless networks, for personal and professional use alike, distributed software systems have become a crucial element in information and communications technologies. The study of these systems forms the core of the ARLES' work, which is specifically concerned with defining new system software architectures, based on the use of emerging networking technologies. In this context, we concentrate on the study of distributed systems which bring to life the vision of ubiquitous computing systems, also known as ambient intelligence.

반도체 공정 overview

The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage, and utilization, dependent on availability and requirement, is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue, and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage, and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways, which are regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors such as dietary composition and feeding frequency, exercise training, and use of pharmacological compounds, influence metabolic flexibility and will be discussed here. Last, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.

Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease.

Background Platinum-based anticancer drugs are widely used in the chemotherapy of human neoplasms. The major obstacle for the clinical use of this class of drugs is the development of resistance and toxicity. It is therefore very important to understand the chemical properties, transport and metabolic pathways and mechanism of actions of these compounds. There is a large body of evidence that therapeutic and toxic effects of platinum drugs on cells are not only a consequence of covalent adducts formation between platinum complexes and DNA but also with RNA and many proteins. These processes determine molecular mechanisms that underlie resistance to platinum drugs as well as their toxicity. Increased expression levels of various transporters and increased repair of platinum-DNA adducts are both considered as the most significant processes in the development of drug resistance. Functional genomics has an increasing role in predicting patients' responses to platinum drugs. Genetic polymorphisms affecting these processes may play an important role and constitute the basis for individualized approach to cancer therapy. Similar processes may also influence therapeutic potential of nonplatinum metal compounds with anticancer activity. Conclusions Cisplatin is the most frequently used platinum based chemotherapeutic agent that is clinically proven to combat different types of cancers and sarcomas.

Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy

Current growth in aquaculture production is parallel with the increasing number of disease outbreaks, which negatively affect the production, profitability, and sustainability of the global aquaculture industry. Vibriosis is among the most common diseases leading to massive mortality of cultured shrimp, fish, and shellfish in Asia. High incidence of vibriosis can occur in hatchery and grow-out facilities, but juveniles are more susceptible to the disease. Various factors, particularly the source of fish, environmental factors (including water quality and farm management), and the virulence factors of Vibrio, influence the occurrence of the disease. Affected fish show weariness, with necrosis of skin and appendages, leading to body malformation, slow growth, internal organ liquefaction, blindness, muscle opacity, and mortality. A combination of control measures, particularly a disease-free source of fish, biosecurity of the farm, improved water quality, and other preventive measures (e.g., vaccination) might be able to control the infection. Although some control measures are expensive and less practical, vaccination is effective, relatively cheap, and easily implemented. In this review, the latest knowledge on the pathogenesis and control of vibriosis, including vaccination, is discussed.

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Vibriosis in Fish: A Review on Disease Development and Prevention

In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides

This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.

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The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers.

High-performance liquid chromatography coupled with tandem mass spectrometry is commonly used for quantitation of analytes in biological matrices, because of the selectivity, sensitivity, and high throughput offered by this technique. However, the presence of both suppression and enhancement of ionization (SEI) by matrix components is an increasingly recognized impediment to accurate results. The existence of SEI indicates that ionization efficiency is a result of the chemical environment seen by both the analyte and internal standard during ion formation. SEI is influenced by the type and the make of ion source used, mobile-phase composition, extent of sample preparation, and the ability to chromatographically separate other compounds that may influence ionization of the analyte and/or internal standard. A comprehensive review of the phenomenon of SEI in high-performance liquid chromatography coupled with tandem mass spectrometry was conducted, and a summary of salient papers relating to therapeutic agents in biological matrices is presented. Suggestions for approaches to minimize, normalize, or assess SEI and its deleterious effect on accuracy and sensitivity, and hence the validity of quantitative results, are provided. Consideration is also given to a strategy to test for SEI, including the number of samples from different sources that are required to adequately test for SEI.

/pdf/enhancement-and-suppression-of-ionization-in-drug-analysis-330x93zrlr.pdf

Enhancement and Suppression of Ionization in Drug Analysis Using HPLC-MS/MS in Support of Therapeutic Drug Monitoring: A Review of Current Knowledge of Its Minimization and Assessment.

Joshua Simmonds

Papers

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers.

Enhancement and Suppression of Ionization in Drug Analysis Using HPLC-MS/MS in Support of Therapeutic Drug Monitoring: A Review of Current Knowledge of Its Minimization and Assessment.