Synthesis,Structure–Activity,and Structure–Stability Relationships of 2‐Substituted‐N‐(4‐oxo‐3‐oxetanyl) N‐Acylethanolamine Acid Amidase (NAAA) Inhibitors

N‐Acylethanolamine acid amidase (NAAA) is a cysteine amidase that preferentially hydrolyzes saturated or monounsaturated fatty acid ethanolamides (FAEs), such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), which are endogenous agonists of nuclear peroxisome proliferator‐activated receptor‐α (PPAR‐α). Compounds that feature an α‐amino‐β‐lactone ring have been identified as potent and selective NAAA inhibitors and have been shown to exert marked anti‐inflammatory effects that are mediated through FAE‐dependent activation of PPAR‐α. We synthesized and tested a series of racemic, diastereomerically pure β‐substituted α‐amino‐β‐lactones, as either carbamate or amide derivatives, investigating the structure–activity and structure–stability relationships (SAR and SSR) following changes in β‐substituent size, relative stereochemistry at the α‐ and β‐positions, and α‐amino functionality. Substituted carbamate derivatives emerged as more active and stable than amide analogues, with the cis configuration being generally preferred for stability. Increased steric bulk at the β‐position negatively affected NAAA inhibitory potency, while improving both chemical and plasma stability.     

Temperature-dependent microtensile testing of thin film materials for application to microelectromechanical system

A specially designed microtensile apparatus capable of carrying out a series of tests on microscale thin films for microelectromechanical system (MEMS) applications at room temperature and at temperature up to 400°C has been developed and tested, and is described here. Several MEMS-applicable thin films were measured with it, including thermally grown silicon dioxide, gold, and gold–vanadium. The silicon dioxide was tested at room temperature. Gold and gold–vanadium films were tested at room temperature and at 200 and 400°C. Examples of these results are presented.     

Electrically Controlled Nano and Micro Actuation in Memristive Switching Devices with On‐Chip Gas Encapsulation

Nanoactuators are a key component for developing nanomachinery. Here, an electrically driven device yielding actuation stresses exceeding 1 MPa withintegrated optical readout is demonstrated. 10 nm thick Al₂O₃ electrolyte films are sandwiched between graphene and Au electrodes. These allow reversible room‐temperature solid‐state redox reactions, producing Al metal and O₂ gas in a memristive‐type switching device. The resulting high‐pressure oxygen micro‐fuel reservoirs are encapsulated under the graphene, swelling to heights of up to 1 µm, which can be dynamically tracked by plasmonic rulers. Unlike standard memristors where the memristive redox reaction occurs in single or few conductive filaments, the mechanical deformation forces the creation of new filaments over the whole area of the inflated film. The resulting on–off resistance ratios reach 10⁸ in some cycles. The synchronization of nanoactuation and memristive switching in these devices is compatible with large‐scale fabrication and has potential for precise and electrically monitored actuation technology.     

Towards a new approach to query search engines: the Search Tree visual language

In this paper, we describe theit Search Tree visual language. It is a novel methodology able to support users to build up complex queries to be run on given search engines. For using this visual language, neither parentheses nor precedence rules are needed, nor the specific ability to perform advanced search tasks. The language is proven to have the same expressive power as the expressions in Sum Of Product form. In order to prove the appropriateness of our proposal, we measured the usability of the proposed querying approach against the traditional Yahoo ^TM web search query language. Results show that, even if both the approaches fully support users in terms of efficacy, the Search Tree visual language significantly improves task efficiency, both in terms of the number of actions performed and the time requested with respect to the advanced search interface. Copyright © 2010 John Wiley & Sons, Ltd.     

Dependability issues in visual–haptic interfaces

Dependability of a system is commonly referred to its reliability, its availability and its maintenability (RAM), but when this concept is applied to user interfaces there is no common agreement on what aspects of user–system interaction are related to a satisfactory RAM level for the whole system. In particular, when dealing with haptic systems, interface dependability may become a crucial issue in medical and in military domains when life-critical systems are to be manipulated or where costly remote control operations are to be performed, like in industrial processes control or in aerospace/automotive engineering and manufacturing. This paper discusses the role of dependability in haptic user interfaces, aiming to the definition of a framework for the assessment of the usability and dependability properties of haptic systems and their possible correlations. The research is based on the analysis of a visual–haptic-based simulator targeted to maintenance activity training for aerospace industry which is taken as a case study. As a result, we propose a novel framework able to collect and then process relevant interaction data during the execution of haptic tasks, enabling to analyze dependability vs. usability correlations.     

Entropy analysis of muscular near-infrared spectroscopy (NIRS) signals during exercise programme of type 2 diabetic patients: Quantitative assessment of muscle metabolic pattern

Diabetes mellitus (DM) is a metabolic disorder that is widely rampant throughout the world population these days. The uncontrolled DM may lead to complications of eye, heart, kidney and nerves. The most common type of diabetes is the type 2 diabetes or insulin-resistant DM.     

Pediatric Celiac Disease Patients Show Alterations of Dendritic Cell Shape and Actin Rearrangement

Celiac disease (CD) is a frequent intestinal inflammatory disease occurring in genetically susceptible individuals upon gluten ingestion. Recent studies point to a role in CD for genes involved in cell shape, adhesion and actin rearrangements, including a Rho family regulator, Rho GTPase-activating protein 31 (ARHGAP31). In this study, we investigated the morphology and actin cytoskeletons of peripheral monocyte-derived dendritic cells (DCs) from children with CD and controls when in contact with a physiological substrate, fibronectin. DCs were generated from peripheral blood monocytes of pediatric CD patients and controls. After adhesion on fibronectin, DCs showed a higher number of protrusions and a more elongated shape in CD patients compared with controls, as assessed by immunofluorescence actin staining, transmitted light staining and video time-lapse microscopy. These alterations did not depend on active intestinal inflammation associated with gluten consumption and were specific to CD, since they were not found in subjects affected by other intestinal inflammatory conditions. The elongated morphology was not a result of differences in DC activation or maturation status, and did not depend on the human leukocyte antigen (HLA)-DQ2 haplotype. Notably, we found that ARH-GAP31 mRNA levels were decreased while RhoA-GTP activity was increased in CD DCs, pointing to an impairment of the Rho pathway in CD cells. Accordingly, Rho inhibition was able to prevent the cytoskeleton rearrangements leading to the elongated morphology of celiac DCs upon adhesion on fibronectin, confirming the role of this pathway in the observed phenotype. In conclusion, adhesion on fibronectin discriminated CD from the controls’ DCs, revealing a gluten-independent CD-specific cellular phenotype related to DC shape and regulated by RhoA activity.     

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy

Moyamoya arteriopathy (MA) is a rare cerebrovascular disorder characterized by ischemic/hemorrhagic strokes. The pathophysiology is unknown. A deregulation of vasculogenic/angiogenic/inflammatory pathways has been hypothesized as a possible pathophysiological mechanism. Since lipids are implicated in modulating neo-vascularization/angiogenesis and inflammation, their deregulation is potentially involved in MA. Our aim is to evaluate angiogenic/vasculogenic/inflammatory proteins and lipid profile in plasma of MA patients and control subjects (healthy donors HD or subjects with atherosclerotic cerebrovascular disease ACVD). Angiogenic and inflammatory protein levels were measured by ELISA and a complete lipidomic analysis was performed on plasma by mass spectrometry. ELISA showed a significant decrease for MMP-9 released in plasma of MA. The untargeted lipidomic analysis showed a cumulative depletion of lipid asset in plasma of MA as compared to HD. Specifically, a decrease in membrane complex glycosphingolipids peripherally circulating in MA plasma with respect to HD was observed, likely suggestive of cerebral cellular recruitment. The quantitative targeted approach demonstrated an increase in free sphingoid bases, likely associated with a deregulated angiogenesis. Our findings indicate that lipid signature could play a central role in MA and that a detailed biomarker profile may contribute to untangle the complex, and still obscure, pathogenesis of MA.     

The Lipid Asset Is Unbalanced in Peripheral Nerve Sheath Tumors

Peripheral nerve sheath tumors (PNSTs) include schwannomas, neurofibromas (NFs), and plexiform neurofibromas (PNFs), among others. While they are benign tumors, according to their biological behavior, some have the potential for malignant degeneration, mainly PNFs. The specific factors contributing to the more aggressive behavior of some PNSTs compared to others are not precisely known. Considering that lipid homeostasis plays a crucial role in fibrotic/inflammatory processes and in several cancers, we hypothesized that the lipid asset was also unbalanced in this group of nerve tumors. Through untargeted lipidomics, NFs presented a significant increase in ceramide, phosphatidylcholine, and Vitamin A ester. PNFs displayed a marked decrease in 34 out of 50 lipid class analyzed. An increased level of ether- and oxidized-triacylglycerols was observed; phosphatidylcholines were reduced. After sphingolipidomic analysis, we observed six sphingolipid classes. Ceramide and dihydroceramides were statistically increased in NFs. All the glycosylated species appeared reduced in NFs, but increased in PNFs. Our findings suggested that different subtypes of PNSTs presented a specific modulation in the lipidic profile. The untargeted and targeted lipidomic approaches, which were not applied until now, contribute to better clarifying bioactive lipid roles in PNS natural history to highlight disease molecular features and pathogenesis.     

Toxicity assessment of nano‐TiO2 in Apis mellifera L., 1758: histological and immunohistochemical assays

The aim of this study was to evaluate the toxicity of titanium dioxide nanoparticles (TiO₂NPs) by short‐term toxicity tests in Apis mellifera, considered an excellent bioindicator organism mainly due to its sensitivity. Bees have been exposed to several concentrations of TiO₂NPs (1 × 10^?3, 1 × 10^?4, 1 × 10^?5, 1 × 10^?6 mg/10 ml) for 10 days. Morphostructural and histological assays were done on gut and honey sac. The research of exposure biomarkers like metallothioneins 1 (MT1) and Heat Shock Protein 70 (HSP70) was performed to verify if a detoxification mechanism has been activated in the exposed animals. No histological alteration on the epithelium of the gut and honey sac were observed in exposed samples. A significant positivity for anti‐MT1 antibody was observed only in the honey sac cells. A weak positivity for HSP70 was observed in both structures analyzed. In several studies have shown the non‐toxicity of TiO₂NPs on other model organisms, in our study, titanium dioxide nanoparticles was proven to be highly toxic at the highest concentration tested (100% of lethality to 1 × 10^?3 mg/10 ml) and moderately toxic at lower concentrations. Honey bees proved to be excellent models for study of NPs toxicity and for monitoring environment.