Peripheral O2 diffusion does not affect V(O2)on-kinetics in isolated insitu canine muscle

To test the hypothesis that muscle O2 uptake (V(O2)) on-kinetics is limited, at least in part, by peripheral O2 diffusion, we determined the V(O2) on-kinetics in 1) normoxia (Control); 2) hyperoxic gas breathing (Hyperoxia); and 3) hyperoxia and the administration of a drug (RSR-13, Allos Therapeutics), which right-shifts the Hb-O2 dissociation curve (Hyperoxia+RSR-13). The study was conducted in isolated canine gastrocnemius muscles (n = 5) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% peak V(O2)). In all conditions, before and during contractions, muscle was pump perfused with constantly elevated blood flow (Q), at a level measured at steady state during contractions in preliminary trials with spontaneous Q x Adenosine was infused intra-arterially to prevent inordinate pressure increases with the elevated Q x Q was measured continuously, arterial and popliteal venous O2 concentrations were determined at rest and at 5- to 7-s intervals during contractions, and V(O2) was calculated as Q x arteriovenous O2 content difference. PO2 at 50% HbO2 saturation (P50) was calculated. Mean capillary PO2 (Pc(O2)) was estimated by numerical integration. P50 was higher in Hyperoxia+RSR-13 [40 +/- 1 (SE) Torr] than in Control and in Hyperoxia (31 +/- 1 Torr). After 15 s of contractions, Pc(O2) was higher in Hyperoxia (97 +/- 9 Torr) vs. Control (53 +/- 3 Torr) and in Hyperoxia+RSR-13 (197 +/- 39 Torr) vs. Hyperoxia. The time to reach 63% of the difference between baseline and steady-state V(O2) during contractions was 24.7 +/- 2.7 s in Control, 26.3 +/- 0.8 s in Hyperoxia, and 24.7 +/- 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement of peripheral O2 diffusion (obtained by increased PcO2 at constant O2 delivery) during the rest-to-contraction (60-70% of peak V(O2)) transition did not affect muscle V(O2) on- kinetics.     

Sentic Computing for social media marketing

In a world in which millions of people express their opinions about commercial products in blogs, wikis, fora, chats and social networks, the distillation of knowledge from this huge amount of unstructured information can be a key factor for marketers who want to create an image or identity in the minds of their customers for their product, brand or organization. Opinion mining for product positioning, in fact, is getting a more and more popular research field but the extraction of useful information from social media is not a simple task. In this work we merge AI and Semantic Web techniques to extract, encode and represent this unstructured information. In particular, we use Sentic Computing, a multi-disciplinary approach to opinion mining and sentiment analysis, to semantically and affectively analyze text and encode results in a semantic aware format according to different web ontologies. Eventually we represent this information as an interconnected knowledge base which is browsable through a multi-faceted classification website.     

Stannate and permanganate conversion coatings on AZ31 magnesium alloy

The formation of stannate and permanganate–phosphate conversion coatings on AZ31 magnesium alloy was investigated in situ by EIS measurements and their protective performances were studied by different electrochemical techniques in diluted (0.05 M) sodium sulphate solution.The influence that short or long treatment times exert on the performances of such conversion coatings is discussed. While permanganate–phosphate baths always built layers characterized by penetrating cracks, long stannate baths produced layers without interconnected porosity, but were defective. This accounted for the initial greater protectiveness achieved with the stannate treatment; nevertheless, the easy penetration of the electrolytic solution through such a layer quickly decreased its corrosion resistance.     

Neuroprotective Effects of Testosterone in the Hypothalamus of an Animal Model of Metabolic Syndrome

Metabolic syndrome (MetS) is known to be associated to inflammation and alteration in the hypothalamus, a brain region implicated in the control of several physiological functions, including energy homeostasis and reproduction. Previous studies demonstrated the beneficial effects of testosterone treatment (TTh) in counteracting some MetS symptoms in both animal models and clinical studies. This study investigated the effect of TTh (30 mg/kg/week for 12 weeks) on the hypothalamus in a high-fat diet (HFD)-induced animal model of MetS, utilizing quantitative RT-PCR and immunohistochemical analyses. The animal model recapitulates the human MetS features, including low testosterone/gonadotropin plasma levels. TTh significantly improved MetS-induced hypertension, visceral adipose tissue accumulation, and glucose homeostasis derangements. Within hypothalamus, TTh significantly counteracted HFD-induced inflammation, as detected in terms of expression of inflammatory markers and microglial activation. Moreover, TTh remarkably reverted the HFD-associated alterations in the expression of important regulators of energy status and reproduction, such as the melanocortin and the GnRH-controlling network. Our results suggest that TTh may exert neuroprotective effects on the HFD-related hypothalamic alterations, with positive outcomes on the circuits implicated in the control of energy metabolism and reproductive tasks, thus supporting a possible role of TTh in the clinical management of MetS.     

High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.     

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.     

Simulating protection rackets: a case study of the Sicilian Mafia

Protection racketeering groups are powerful, deeply entrenched in multiple societies across the globe, and they harm the societies and economies in which they operate in multiple ways. These reasons make their dynamics important to understand and an objective of both scientific and application-oriented interest. Legal and social norm-based approaches arguably play significant roles in influencing protection racket dynamics. We propose an agent-based simulation model, the Palermo Scenario, to enrich our understanding of these influences and to test the effect of different policies on protection racket dynamics. Our model integrates the legal and the social norm-based approaches and uses a complex normative agent architecture that enables the analysis of both agents’ behaviours and mental normative representations driving behaviour. We demonstrate the usefulness of the model and the benefits of using this complex normative architecture through a case study of the Sicilian Mafia.     

Fibroblast protein profile analysis highlights the role of oxidative stress and vitamin K recycling in the pathogenesis of pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a genetic disorder associated to mutations in the ABCC6 gene; however, the pathogenetic mechanisms leading to elastic fibre calcifications and to clinical manifestations are still unknown. Dermal fibroblasts, directly involved in the production of the extracellular milieu, have been isolated from healthy subjects and from patients affected by PXE, cultured in vitro and characterized for their ability to produce reactive oxygen species, for structural and functional properties of their cell membranes, for changes in their protein profile. Data demonstrate that oxidative stress has profound and endurable consequences on PXE fibroblast phenotype being responsible for: reduced levels of global DNA methylation, increased amount of carbonylated proteins and of lipid peroxidation products, altered structural properties of cell membranes, modified protein expression. Data shed new light on the pathogenetic pathways in PXE, by identifying a network of proteins affecting elastic fibre calcification through inefficient vitamin K recycling, and highlight the role of differentially expressed proteins as targets for validating the efficacy of future therapeutic strategies aiming to delay and/or revert the pathologic phenotype of PXE fibroblasts. Moreover, data open new perspectives for investigating PXE-like phenotypes in the absence of ABCC6 mutations.     

Travel time models for deep-lane unit-load autonomous vehicle storage and retrieval system (AVS/RS)

Autonomous vehicle storage and retrieval systems use vehicles that move horizontally along rails within the storage racks, while vertical movements are provided by lifts. The solution proposed in this paper addresses a particular system configuration that works with multiple deep storage lanes that are widely used in the food and beverage industry, characterised by large volumes of products of limited variety. The generic deep lane is single item, i.e. one stock keeping unit, and single batch, i.e. one production lot, thereby affecting the performance of the system in terms of storage capacity utilisation and throughput. Determining the number and depth of the lanes is crucial to aid the design and control of such a storage system. The aim of this paper was to support the design of AVS/RSs though a set of original analytic models for the determination of the travelled distance and time for single-command and dual-command cycles given alternative layout configurations. The models are validated by simulation and exemplified with a real-warehousing case study. The paper presents useful guidelines for the configuration of the system layout including the determination of the optimal shape ratio and the length of the lanes.