Towards 5G Software-Defined Ecosystems: Technical Challenges, Business Sustainability and Policy Issues

Techno-economic drivers are creating the conditions for a radical change of paradigm in the design and operation of future telecommunications infrastructures. In fact, SDN, NFV, Cloud and Edge-Fog Computing are converging together into a single systemic transformation termed “Softwarization” that will find concrete exploitations in 5G systems. The IEEE SDN Initiative1 has elaborated a vision, an evolutionary path and some techno-economic scenarios of this transformation: specifically, the major technical challenges, business sustainability and policy issues have been investigated. This white paper presents: 1) an overview on the main techno-economic drivers steering the “Softwarization” of telecommunications; 2) an introduction to the Open Mobile Edge Cloud vision (covered in a companion white paper); 3) the main technical challenges in terms of operations, security and policy; 4) an analysis of the potential role of open source software; 5) some use case proposals for proof-of-concepts; and 6) a short description of the main socio-economic impacts being produced by “Softwarization”. Along these directions, IEEE SDN is also developing of an open catalogue of software platforms, toolkits, and functionalities aiming at a step-by-step development and aggregation of test-beds/field-trials on SDNNFV- 5G

Plasma Kallikrein Mediates Retinal Vascular Dysfunction and Induces Retinal Thickening in Diabetic Rats

Objective: Plasma kallikrein (PK) has been identified in vitreous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dysfunction. In this report, we examined the effects of PK on retinal vascular functions and thickness in diabetic rats. Research Design and Methods: We investigated the effects of a selective PK inhibitor, ASP-440, and C1 inhibitor (C1-INH), the primary physiological inhibitor of PK, on retinal vascular permeability (RVP) and hemodynamics in rats with streptozotocin-induced diabetes. The effect of intravitreal PK injection on retinal thickness was examined by spectral domain optical coherence tomography. Results: Systemic continuous administration of ASP-440 for 4 weeks initiated at the time of diabetes onset inhibited RVP by 42% (P = 0.013) and 83% (P < 0.001) at doses of 0.25 and 0.6 mg/kg per day, respectively. Administration of ASP-440 initiated 2 weeks after the onset of diabetes ameliorated both RVP and retinal blood flow abnormalities in diabetic rats measured at 4 weeks’ diabetes duration. Intravitreal injection of C1-INH similarly decreased impaired RVP in rats with 2 weeks’ diabetes duration. Intravitreal injection of PK increased both acute RVP and sustained focal RVP (24 h postinjection) to a greater extent in diabetic rats compared with nondiabetic control rats. Intravitreal injection of PK increased retinal thickness compared with baseline to a greater extent (P = 0.017) in diabetic rats (from 193 $\pm$ 10 $\mu$m to 223 $\pm$ 13 $\mu$m) compared with nondiabetic rats (from 182 $\pm$ 8 $\mu$m to 193 $\pm$ 9 $\mu$m). Conclusions: These results show that PK contributes to retinal vascular dysfunctions in diabetic rats and that the combination of diabetes and intravitreal injection of PK in rats induces retinal thickening

Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition

Diabetic retinopathy is a leading cause of adult vision loss and blindness. Much of the retinal damage that characterizes the disease results from retinal vascular leakage and nonperfusion. This study shows that diabetic retinal vascular leakage and nonperfusion are temporally and spatially associated with retinal leukocyte stasis (leukostasis) in the rat model of streptozotocin-induced diabetes. Retinal leukostasis increases within days of developing diabetes and correlates with the increased expression of retinal intercellular adhesion molecule-1 (ICAM-1). ICAM-1 blockade with a mAb prevents diabetic retinal leukostasis and vascular leakage by 48.5% and 85.6%, respectively. These data identify the causal role of leukocytes in the pathogenesis of diabetic retinopathy and establish the potential utility of ICAM-1 inhibition as a therapeutic strategy for the prevention of diabetic retinopathy

The effect of Puerariae radix on lipoprotein metabolism in liver and intestinal cells

BACKGROUND: Animal studies investigating the beneficial effects of Puerariae radix on cardiovascular disease have suggested this plant possesses anti-diabetic and lipid lowering properties. However, the exact mechanism by which Puerariae radix affects lipid metabolism is currently unknown. The aim of this study was to investigate the effect of the water extract of Puerariae radix on the secretion of VLDL and chylomicrons from HepG2 liver cells and CaCo2 cells, respectively, in humans. METHODS: The amount of apoB(100 )(a protein marker for VLDL) and apoB(48 )(a protein marker for chylomicrons) in cells and media were quantified by Western Blotting and enhanced chemiluminescence (ECL). Total, free and esterified cholesterol concentrations were measured by gas liquid chromatography. RESULTS: Treatment of cells with water extract of Puerariae radix significantly decreased apoB(100 )production and secretion from HepG2 cells up to 66% in a dose dependent manner. The intracellular total cholesterol and free cholesterol concentration in HepG2 cells also decreased with increasing concentration of the Puerariae radix. In contrast, water extract of Puerariae radix attenuated apoB(48 )concentrations in cells, but not apoB(48 )secretion from CaCo2 enterocytes. CONCLUSIONS: Collectively, our findings suggest that the water extract of Puerariae radix attenuates the hepatic lipoprotein production and secretion. Our present cell culture findings may explain why circulating VLDL and LDL levels were attenuated in animals supplemented with Puerariae radix. Since decreasing the production and secretion of atherogenic lipoproteins decreases the risk of development of cardiovascular disease, diets supplemented with radix may provide a safe and effective beneficial cardioprotective effects in humans

Evaluation of host-derived volatiles for trapping Culicoides biting midges (Diptera: Ceratopogonidae)

Culicoides biting midges (Diptera: Ceratopognidae) cause pain and distress through blood feeding, and transmit viruses that threaten both animal and human health worldwide. There are few effective tools for monitoring and control of biting midges, with semiochemical-based strategies offering the advantage of targeting host-seeking populations. In previous studies, we identified the host preference of multiple Culicoides species, including Culicoides impunctatus, as well as cattle-derived compounds that modulate the behavioral responses of C. nubeculosus under laboratory conditions. Here, we test the efficacy of these compounds, when released at different rates, in attracting C. impunctatus under field conditions in Southern Sweden. Traps releasing 1-octen-3-ol, decanal, phenol, 4-methylphenol or 3-propylphenol, when combined with carbon dioxide (CO2), captured significantly higher numbers of C. impunctatus compared to control traps baited with CO2 alone, with low release rates (0.1 mg h−1, 1 mg h−1) being generally more attractive. In contrast, traps releasing octanal or (E)-2-nonenal at 1 mg h−1 and 10 mg h−1 collected significantly lower numbers of C. impunctatus than control traps baited with CO2 only. Nonanal and 2-ethylhexanol did not affect the attraction of C. impunctatus when compared to CO2 alone at any of the release rates tested. The potential use of these semiochemicals as attractants and repellents for biting midge control is discussed

Riboflavin alleviates cardiac failure in Type I diabetic cardiomyopathy

Heart failure (HF) is a common and serious comorbidity of diabetes. Oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. Riboflavin constitutes an essential nutrient for humans and animals and it is an important food additive. Riboflavin, a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), enhances the oxidative folding and subsequent secretion of proteins. The objective of this study was to investigate the cardioprotective effect of riboflavin in diabetic rats. Diabetes was induced in 30 rats by a single injection of streptozotocin (STZ) (70 mg /kg). Riboflavin (20 mg/kg) was orally administered to animals immediately after induction of diabetes and was continued for eight weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV) remadynamic function. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), the level of malondialdehyde (MDA) as well as heme oxygenase-1 (HO-1) protein level. Myocardial connective tissue growth factor (CTGF) level was measured by Western blot in all rats at the end of the study. In the untreated diabetic rats, left ventricular systolic pressure (LVSP) rate of pressure rose (+dp/dt), and rate of pressure decay (−dp/dt) were depressed while left ventricular end-diastolic pressure (LVEDP) was increased, which indicated the reduced left ventricular contractility and slowing of left ventricular relaxation. The level of SOD decreased, CTGF and HO-1 protein expression and MDA content rose. Riboflavin treatment significantly improved left ventricular systolic and diastolic function in diabetic rats, there were persistent increases in significant activation of SOD and the level of HO-1 protein, and a decrease in the level of CTGF. These results suggest that riboflavin treatment ameliorates myocardial function and improves heart oxidant status, whereas raising myocardial HO-1 and decreasing myocardial CTGF levels have beneficial effects on diabetic cardiomyopathy

A Multi-Host Agent-Based Model for a Zoonotic, Vector-Borne Disease. A Case Study on Trypanosomiasis in Eastern Province, Zambia

Background: This paper presents a new agent-based model (ABM) for investigating T. b. rhodesiense human African trypanosomiasis (rHAT) disease dynamics, produced to aid a greater understanding of disease transmission, and essential for development of appropriate mitigation strategies. Methods: The ABM was developed to model rHAT incidence at a fine spatial scale along a 75 km transect in the Luangwa Valley, Zambia. The method offers a complementary approach to traditional compartmentalised modelling techniques, permitting incorporation of fine scale demographic data such as ethnicity, age and gender into the simulation. Results: Through identification of possible spatial, demographic and behavioural characteristics which may have differing implications for rHAT risk in the region, the ABM produced output that could not be readily generated by other techniques. On average there were 1.99 (S.E. 0.245) human infections and 1.83 (S.E. 0.183) cattle infections per 6 month period. The model output identified that the approximate incidence rate (per 1000 person-years) was lower amongst cattle owning households (0.079, S.E. 0.017), than those without cattle (0.134, S.E. 0.017). Immigrant tribes (e.g. Bemba I.R. = 0.353, S.E.0.155) and school-age children (e.g. 5–10 year old I.R. = 0.239, S.E. 0.041) were the most at-risk for acquiring infection. These findings have the potential to aid the targeting of future mitigation strategies. Conclusion: ABMs provide an alternative way of thinking about HAT and NTDs more generally, offering a solution to the investigation of local-scale questions, and which generate results that can be easily disseminated to those affected. The ABM can be used as a tool for scenario testing at an appropriate spatial scale to allow the design of logistically feasible mitigation strategies suggested by model output. This is of particular importance where resources are limited and management strategies are often pushed to the local scale. © 2016 Alderton et al

Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity

Aquaglyceroporins (AQPs) transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock. The aqp1-2-3 trypanosomes did, however, display glycerol uptake and efflux defects. They failed to accumulate glycerol or to utilise glycerol as a carbon-source and displayed increased sensitivity to salicylhydroxamic acid (SHAM), octyl gallate or propyl gallate; these inhibitors of trypanosome alternative oxidase (TAO) can increase intracellular glycerol to toxic levels. Notably, disruption of AQP2 alone generated cells with glycerol transport defects. Consistent with these findings, AQP2-defective, melarsoprol-resistant clinical isolates were sensitive to the TAO inhibitors, SHAM, propyl gallate and ascofuranone, relative to melarsoprol-sensitive reference strains. We conclude that African trypanosome AQPs are dispensable for viability and osmoregulation but they make important contributions to drug-uptake, glycerol-transport and respiratory-inhibitor sensitivity. We also discuss how the AQP-dependent inverse sensitivity to melarsoprol and respiratory inhibitors described here might be exploited