A TD-LTE Prototype System with Modules for General-Purpose Cognitive Resource Management and Radio-Environmental Mapping

In this article we describe a demonstrator that shows how the cognitive resource manager (CRM) and the radio-environmental map (REM) can be efficiently implemented in full commercial grade cellular system (i.e., LTE system). The demonstrator shows how the modular CRM together with its open interface, the universal link-layer API (ULLA), facilitates the implementation of efficient radio resource management techniques guaranteeing the quality of service in the LTE system. The CRM, through ULLA, is able to obtain PHY/MAC status information of the link between the tested eNode B and the user equipment, and reconfigure link parameters. This measure-and-control by CRM/ULLA is independent of the underlying radio access technology, which shows the neutrality of CRM/ULLA towards PHY/MAC characteristics. The article also shows how the REM can be easily implemented in such system and how the REM provides the CRM with environmental information that enhances system management performance.     

Long Noncoding RNA GAS5 in Breast Cancer: Epigenetic Mechanisms and Biological Functions

Long noncoding RNAs (lncRNAs) have been identified as contributors to the development and progression of cancer through various functions and mechanisms. LncRNA GAS5 is downregulated in multiple cancers and acts as a tumor suppressor in breast cancer. GAS5 interacts with various proteins (e.g., E2F1, EZH2, and YAP), DNA (e.g., the insulin receptor promoter), and various microRNAs (miRNAs). In breast cancer, GAS5 binds with miR-21, miR-222, miR-221-3p, miR-196a-5p, and miR-378a-5p that indicates the presence of several elements for miRNA binding (MREs) in GAS5. Mediated by the listed miRNAs, GAS5 is involved in the upregulation of a number of mRNAs of suppressor proteins such as PTEN, PDCD4, DKK2, FOXO1, and SUFU. Furthermore, the aberrant promoter methylation is involved in the regulation of GAS5 gene expression in triple-negative breast cancer and some other carcinomas. GAS5 can stimulate apoptosis in breast cancer via diverse pathways, including cell death receptors and mitochondrial signaling pathways. GAS5 is also a key player in the regulation of some crucial signal pathways in breast cancer, such as PI3K/AKT/mTOR, Wnt/β-catenin, and NF-κB signaling. Through epigenetic and other mechanisms, GAS5 can increase sensitivity to multiple drugs and improve prognosis. GAS5 is thus a promising target in the treatment of breast cancer patients.     

Optimization and Validation of a Fluorescence Polarization Immunoassay for Rapid Detection of T-2 and HT-2 Toxins in Cereals and Cereal-Based Products

A fluorescence polarization (FP) immunoassay has been optimized and validated for rapid quantification of T-2 and HT-2 toxins in both unprocessed cereals, including oats, barley and rye, and cereal-based products for direct human consumption, such as oat flakes, oats crispbread and pasta. Samples were extracted with 90 % methanol, and the extract was filtered and diluted with water or sodium chloride solution prior to the FP immunoassay. Overall mean recoveries from spiked oats, rye, barley, oat flakes, oats crispbread and pasta ranged from 101 to 107 %, with relative standard deviations lower than 7 %. Limits of detection (LODs) of the FP immunoassay were 70 μg/kg for oats, 40 μg/kg for oat flakes and barley, 25 μg/kg for pasta and 20 μg/kg for rye and oats crispbread. The trueness of the immunoassay was assessed by using two oat and oat flake reference materials for T-2 and HT-2 toxins, showing good accuracy and precision. Good correlations (r?>?0.953) were observed between T-2 and HT-2 toxin contents in naturally and artificially contaminated samples determined by both FP immunoassay and ultra-high-performance liquid chromatography (UHPLC) with immunoaffinity column cleanup used as reference method. These results, combined with rapidity and simplicity of the assay, show that the optimized assay is suitable for high-throughput screening, as well as for reliable quantitative determination of T-2 and HT-2 toxins in cereals and cereal-based products.     

Bacteriocin production by Enterococcus faecium FAIR-E 198 in view of its application as adjunct starter in Greek Feta cheese making

Bacteriocin production by Enterococcus faecium FAIR-E 198, isolated from Greek Feta cheese, was studied in batch fermentations, under conditions simulating Feta cheese preparation. Maximum enterocin activity and growth rate was obtained in de Man-Rogosa-Sharpe (MRS) broth at 37 degrees C with controlled pH 6.5. The enterocin was produced throughout the growth phase of the microorganism, showing primary metabolite kinetics with a peak activity during the mid-exponential phase. The use of skimmed milk as substrate revealed low enterocin activity. When fermentations were performed in skimmed milk in the presence of rennet, CaCl2, and a mixed starter culture, no enterocin activity was observed, although the examined strain grew well under the above conditions. Finally, when E. faecium FAIR-E 198 was applied as adjunct starter in Feta cheese making, no enterocin activity was detected throughout ripening. Results obtained underline the frequently underestimated finding that in vitro production by novel bacteriocinogenic starter or co-cultures is no guarantee for in situ efficiency. It was concluded that the complex food environment thoroughly interferes with bacteriocin production levels.     

Changes in firmness and thermal behavior of ice-stored muscle of jumbo squid (<Emphasis Type="Italic">Dosidicus gigas</Emphasis>)

Changes in firmness, muscle total protease activity, and the thermal behavior of jumbo squid (Dosidicus gigas) were measured throughout 15 days of ice-storage. A significant decrease (p<0.05) in the shear force of raw mantle muscle was observed after 7-days ice-storage. The highest total protease activity detected was 1.24 U/g mantle. The thermograms obtained at day zero showed four transition states. The first three transition states were endothermic and correspond to myosin (50 °C), sarcoplasmic proteins (69 °C), and actin (79 °C). The fourth transition state was exothermic at 107 °C, and was probably associated with protein aggregation. The thermal behavior of the muscle showed a decreasing trend in temperature and enthalpy of transition for myosin, sarcoplasmic proteins, and actin with storage time. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis showed a change in the myofibrillar protein pattern, which with the shear force, and differential scanning calorimetry data, suggests a partial denaturation of that protein fraction during ice-storage.     

Conjugated linoleic acid (CLA) effects on pups growth, milk composition and lipogenic enzymes in lactating rats

Conjugated linoleic acid (CLA) has a range of biological properties, including effects on lipid metabolism, milk and body composition in animals. This study investigated the effects of dietary CLA on lactating rats and development of the suckling pups. Dams were fed either a control diet or the same diet supplemented with 25 g/kg of a fat supplement containing 540 g CLA/kg (final concentration of 13.5 g CLA/kg diet) from parturition to the 15th day post-partum. The CLA mixture used in this study contained the following isomers (per 100 g): cis-9, trans-11 (24 g); cis-10, trans-12 (35 g); cis-8, trans-10 (15 g); cis-11, trans-13 (17 g) and others (9 g). On d 15 post partum, CLA supplementation reduced milk fat content by 33% and pup growth by 21%. The milk fatty acid profile, with decreased content of short and medium chain acids, suggests CLA inhibition was more pronounced for de novo lipid synthesis. Consistent with these results, activities of fatty acid synthase, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were reduced by CLA treatment in the mammary gland and liver. In contrast, the activity of NADP-malate dehydrogenase was unchanged.     

Exploratory Metabolomic Analysis Based on Reversed-Phase Liquid Chromatography–Mass Spectrometry to Study an In Vitro Model of Hypoxia-Induced Metabolic Alterations in HK-2 Cells

Oxygen deficiency in cells, tissues, and organs can not only prevent the proper development of biological functions but it can also lead to several diseases and disorders. In this sense, the kidney deserves special attention since hypoxia can be considered an important factor in the pathophysiology of both acute kidney injury and chronic kidney disease. To provide better knowledge to unveil the molecular mechanisms involved, new studies are necessary. In this sense, this work aims to study, for the first time, an in vitro model of hypoxia-induced metabolic alterations in human proximal tubular HK-2 cells because renal proximal tubules are particularly susceptible to hypoxia. Different groups of cells, cultivated under control and hypoxia conditions at 0.5, 5, 24, and 48 h, were investigated using untargeted metabolomic approaches based on reversed-phase liquid chromatography–mass spectrometry. Both intracellular and extracellular fluids were studied to obtain a large metabolite coverage. On the other hand, multivariate and univariate analyses were carried out to find the differences among the cell groups and to select the most relevant variables. The molecular features identified as affected metabolites were mainly amino acids and Amadori compounds. Insights about their biological relevance are also provided.     

Chitosan interaction with iron from yoghurt using an in vitro digestive model: comparative study with plant dietary fibers

The objective of this work was to investigate the interaction of chitosan with iron from yoghurt by an in vitro gastrointestinal tract model. Taking into account that chitosan is a polysaccharide included in fiber definition by Codex Alimentarius; chitosan behavior was studied and compared with different plant fiber (wheat, bamboo, apple, psyllium and inulin) behaviors, in the same in vitro conditions. Ferrous sulfate was added to yoghurts with each type of fiber. The gastric environment was simulated with HCl (pH 1.0-2.0). The duodenal environment was simulated with NaHCO(3) (pH 6.8-7.2) and a dialysis tubing cellulose membrane. Results showed that chitosan had the highest iron retention percentages (53.2% at 30 min; 56.8% at 60 min) interacting in a more pronounced manner with iron than the plant fibers used in this work.     

Design, synthesis, ADME properties, and pharmacological activities of β-alanyl-D-histidine (D-carnosine) prodrugs with improved bioavailability

β-Alanyl-D-histidine (D-CAR, the enantiomer of the natural dipeptide carnosine) is a selective and potent sequestering agent of reactive carbonyl species (RCS) that is stable against carnosinase, but is poorly absorbed in the gastrointestinal tract. Herein we report a drug discovery approach aimed at increasing the oral bioavailability of D-CAR. In our study we designed, synthesized, and evaluated a series of novel lipophilic D-CAR prodrugs. The considered prodrugs can be divided into two categories: 1) derivatives with both terminal groups modified, in which the carboxyl terminus is always esterified while the amino terminus is protected by an amidic (N-acetyl derivatives) or a carbamate (ethyloxy or benzyloxy derivatives) function; 2) derivatives with only one terminus modified, which can be alkyl esters as well as amidic or carbamate derivatives. The prodrugs were designed considering their expected lipophilicity and their hydrolysis predicted by docking simulations on the most important human carboxylesterase (hCES1). The stability and metabolic profile of the prodrugs were studied by incubating them with rat and human serum and liver fractions. The octyl ester of D-CAR (compound 13) was chosen as a candidate for further pharmacological studies due to its rapid hydrolysis to the bioactive metabolite in vitro. Pharmacokinetic studies in rats confirmed the in vitro data and demonstrated that the oral bioavailability of D-CAR is increased 2.6-fold if given as an octyl ester relative to D-CAR. Compound 13 was then found to dose-dependently (at daily doses of 3 and 30 mg kg(-1) equivalent of D-CAR) decrease the development of hypertension and dyslipidemia, to restore renal functions of Zucker fa/fa obese rats, and to inhibit the carbonylation process (AGEs and pentosidine) as well as oxidative stress (urinary 8-epi-prostaglandin F2α and nitrotyrosine). A plausible mechanism underlying the protective effects of 13 is RCS sequestration, as evidenced by the significant increase in the level of adduct between CAR and 4-hydroxy-trans-2-nonenal (HNE, the main RCS generated by lipid oxidation) in the urine of treated animals.