Dihydrotanshinone,a Natural Diterpenoid,Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor

Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.     

Energy and comfort: A new type for TRNSYS

Two subroutines have been developed which permit users of the TRNSYS programme to calculate the parameters of ambiental comfort (PMV and PPD).The first subroutine deals with the calculation of the view factors inside a room for all the values of the spatial coordinates and, thus, permits the average radiant temperature to be calculated in every position. The second subroutine has been developed in accordance with the indications of the ISO 7730 standard.Both subroutines have been validated and then interfaced to TRNSYS.The integrated programme has been utilised to compare the performances of different heating systems in terms of energy consumption and comfort, maintaining the temperature of the interior constant for different climatic conditions.     

The KlaperSuite framework for model-driven reliability analysis of component-based systems

Automatic prediction tools play a key role in enabling the application of non-functional requirements analysis, to simplify the selection and the assembly of components for component-based software systems, and in reducing the need for strong mathematical skills for software designers. By exploiting the paradigm of Model-Driven Engineering (MDE), it is possible to automatically transform design models into analytical models, thus enabling formal property verification. MDE is the core paradigm of the KlaperSuite framework presented in this paper, which exploits the KLAPER pivot language to fill the gap between design and analysis of component-based systems for reliability properties. KlaperSuite is a family of tools empowering designers with the ability to capture and analyze quality of service views of their systems, by building a one-click bridge towards a number of established verification instruments. In this article, we concentrate on the reliability-prediction capabilities of KlaperSuite and we evaluate them with respect to several case studies from literature and industry.     

Report of the Second Workshop on the Usage of NetFlow/IPFIX in Network Management

Following the success of the First Workshop on the Usage of NetFlow/IPFIX (Pras et al. in J Netw Syst Manag 17(4), 2009) in 2008, the European EMANICS Network of Excellence organized a second workshop in October 2009, held at Jacobs University Bremen. This report summarizes the workshop and presents its main conclusions.     

Iterative performance improvement of fuzzy control systems for three tank systems

This paper suggests the performance improvement of fuzzy control systems (FCSs) for three tank systems using iterative feedback tuning (IFT). The stable design of Takagi–Sugeno–Kang fuzzy controllers is guaranteed by means of a stability theorem based on LaSalle’s global invariant set theorem formulated for a class of multi input-multi output (MIMO) nonlinear processes. An IFT algorithm characterized by setting the step size to guarantee the FCS stability is proposed. The theoretical approaches are applied in a case study that deals with the IFT-based stable design of fuzzy controllers dedicated to the level control of a cylindrical three tank system as a representative MIMO system. A set of experimental results for a laboratory setup illustrates the performance improvement.     

Precooked sorghum flour as proper vehicle of ACE-I and DPP-IV inhibitory sorghum peptides

Sorghum flour was heat treated for producing an instant dispersion ingredient. The precooked sorghum flour was added with ACE-I and DPP-IV inhibitory sorghum peptides (3.0 g peptide 100 g⁻¹). The product was reconstituted in water, and peptide bioaccessibility was evaluated by equilibrium dialysis method after simulated gastrointestinal digestion. Total peptide dialysability of precooked sorghum flour added with sorghum peptides was higher than those obtained for precooked sorghum flour (315.9 ± 14.8 vs. 45.2 ± 5.6 µmol, respectively) (P < 0.05). The ACE-I and DPP-IV-IC₅₀ values of the bioaccessible peptides from the bioactive product were lower than those obtained for precooked sorghum flour ingredient (1.04 ± 0.12 vs. 1.82 ± 0.09 and 0.86 ± 0.02 vs. 2.12 ± 0.08 mg protein mL⁻¹, for ACE-I and DPP-IV, respectively) indicating a higher activity. Precooked sorghum flour was a good vehicle since it did not affect the bioaccessibility of ACE-I and DPP-IV inhibitory peptides provided by sorghum protein hydrolysate.     

Influence of pH on colour and iron content of peptide fractions obtained from bovine Hb concentrate hydrolysates

The effect of pH on colour and iron content (Fe) of peptide fractions obtained from bovine haemoglobin concentrate (BHC) hydrolysates was studied. Four hydrolysates were obtained using three enzymes: Protex‐6‐L (P), Fungal–Protease–Concetrate (FC) and Flavourzyme (F). BHC and its hydrolysates (P, FC, P + F, FC + F) were fractioned at pH 4.5, 7.0 and 9.5. Solubility and Fe from different fractions were measured. Correlations between CIELAB colour parameters and Fe from different fractions were analysed. The colour from different fractions varied from red to yellow (a* and b* positives). Lightness values (L*) ranged from twenty‐four to seventy. FC4.5 and FC + F4.5 fractions were the clearest and yellow (higher L*, b*, h), while BHC9.5 and P + F9.5 fractions had the lowest values of L*, b* and h. There was an inverse linear relationship between b* and L* parameters and Fe from fractions. This relationship could be associated with the pH of extraction. As pH increases Fe significantly increases and lower b* and L* values were obtained.     

Physical and nutritional properties of extruded products based on whole grain with the addition of wild legumes (Vicia lutea subsp. lutea var. hirta and Vicia sativa subsp. sativa)

Flour blends based on whole corn and rice with two added wild legumes at 15% level of cereal replacement were extruded to produce whole grain snacks. Extrusion temperature was 175 °C, and the moisture content was adjusted to 14%. The extruded products were evaluated for their physical, chemical and nutritional properties. Results showed that the addition of legumes produces a decrease in expansion in rice‐containing samples and an increase in solubility in corn‐containing samples. With only 15% of legume added to cereal, a significant increase in protein content and quality was obtained. An increase in fibre, polyphenol, iron and zinc content was also obtained. Protein digestibility was in the range of 81.8–85.3%. Mineral availability ranged from 6.4 to 16.3% for iron and 10–16.3% for zinc. The performance of each mixture during extrusion and the physical properties of the extruded products were considered to be similar to those expected for snack‐type products and described in the literature.     

Micromechanics of spatially uniform heterogeneous media: A critical review and emerging approaches

Outside of the classical microstructural detail-free estimates of effective moduli, micromechanical analyses of macroscopically uniform heterogeneous media may be grouped into two categories based on different geometric representations of material microstructure. Analysis of periodic materials is based on the repeating unit cell (RUC) concept and the associated periodic boundary conditions. This contrasts with analysis of statistically homogeneous materials based on the representative volume element (RVE) concept and the associated homogeneous boundary conditions. In this paper, using the above classification framework we provide a critical review of the various micromechanical approaches that had evolved along different paths, and outline recent emerging trends. We begin with the basic framework for the solution of micromechanics problems independent of microstructural representation, and then clarify the often confused RVE and RUC concepts. Next, we describe classical models, including the available RVE-based models, and critically examine their limitations. This is followed by discussion of models based on the concept of microstructural periodicity. In the final part, two recent unit cell-based models, which continue to evolve, are outlined. First, a homogenization technique called finite-volume direct averaging micromechanics theory is presented as a viable and easily implemented alternative to the mainstream finite-element based asymptotic homogenization of unit cells. The recent incorporation of parametric mapping into this approach has made it competitive with the finite-element method. Then, the latest work based on locally-exact solutions of unit cell problems is described. In this approach, the interior unit cell problem is solved exactly using the elasticity approach. The exterior problem is tackled with a new variational principle that successfully overcomes the non-separable nature of the overall unit cell problem.