State space reduction by non-standard semantics for deadlock analysis

In recent years many techniques have been developed for automatically verifying concurrent systems and most of them are based on the representation of the concurrent system by means of a transition system. State explosion is one of the most serious problems of this approach: often the prohibitive number of states renders the verification inefficient and, in some cases, impossible.

We propose a method for reducing the state space of the transition system corresponding to a CCS process that suites deadlock analysis. The reduced transition system is generated by means of a non-standard operational semantics containing a set of rules which are, in some sense, an abstraction, preserving deadlock freeness, of the inference rules of the standard semantics. Our method does not build the standard transition system, but directly generates an abstract system with a fewer number of states, so saving memory space. We characterize a class of processes whose abstract transition system is not exponential in the number of parallel components.     

Glass Fiber Reinforced Polymer Pultruded Members: Constitutive Model and Stability Analysis

The increasingly widespread use of fiber-reinforced polymers as an alternative to conventional materials makes it necessary to formulate theoretical models which adequately evaluate the influence of the anisotropy of such composites on the structural behavior. While the cross section shapes adopted for compressed members are generally the same as in steel structures, the anisotropy which characterizes these polymers may reduce the critical loading threshold due to local buckling phenomena. A procedure to study the buckling of glass fiber reinforced polymer pultruded members by means of an homogenization approach is proposed here. A two-stage buckling model permits the determination of both global and local critical loads as explicit functions of the member geometry and its material behavior. These functions may be used for optimization of the shape of the above-mentioned members. Besides the model shows its reliability as it fits the results of experimental testson members with different slenderness ratios.     

Real-time networked control of an industrial robot manipulator via discrete-time second-order sliding modes

This article presents the networked control of a robotic anthropomorphic manipulator based on a second-order sliding mode technique, where the control objective is to track a desired trajectory for the manipulator. The adopted control scheme allows an easy and effective distribution of the control algorithm over two networked machines. While the predictability of real-time tasks execution is achieved by the Soft Hard Real-Time Kernel (S.Ha.R.K.) real-time operating system, the communication is established via a standard Ethernet network. The performances of the control system are evaluated under different experimental system configurations using, to perform the experiments, a COMAU SMART3-S2 industrial robot, and the results are analysed to put into evidence the robustness of the proposed approach against possible network delays, packet losses and unmodelled effects.     

Automated approaches for analysis of multimodal MRI acquisitions in a study of cognitive aging

In this work we describe an integrated and automated workflow for a comprehensive and robust analysis of multimodal MR images from a cohort of more than hundred subjects. Image examinations are done three years apart and consist of 3D high-resolution anatomical images, low resolution tensor-valued DTI recordings and 4D resting state fMRI time series. The integrated analysis of the data requires robust tools for segmentation, registration and fiber tracking, which we combine in an automated manner. Our automated workflow is strongly desired due to the large number of subjects. Especially, we introduce the use of histogram segmentation to processed fMRI data to obtain functionally important seed and target regions for fiber tracking between them. This enables analysis of individually important resting state networks. We also discuss various approaches for the assessment of white matter integrity parameters along tracts, and in particular we introduce the use of functional data analysis (FDA) for this task.     

Presynaptic Inhibition of Pain and Touch in the Spinal Cord: From Receptors to Circuits

Sensory primary afferent fibers, conveying touch, pain, itch, and proprioception, synapse onto spinal cord dorsal horn neurons. Primary afferent central terminals express a wide variety of receptors that modulate glutamate and peptide release. Regulation of the amount and timing of neurotransmitter release critically affects the integration of postsynaptic responses and the coding of sensory information. The role of GABA (γ-aminobutyric acid) receptors expressed on afferent central terminals is particularly important in sensory processing, both in physiological conditions and in sensitized states induced by chronic pain. During the last decade, techniques of opto- and chemogenetic stimulation and neuronal selective labeling have provided interesting insights on this topic. This review focused on the recent advances about the modulatory effects of presynaptic GABAergic receptors in spinal cord dorsal horn and the neural circuits involved in these mechanisms.     

Proteomic Analysis of Marinesco–Sjogren Syndrome Fibroblasts Indicates Pro-Survival Metabolic Adaptation to SIL1 Loss

Marinesco–Sjogren syndrome (MSS) is a rare multisystem pediatric disorder, caused by loss-of-function mutations in the gene encoding the endoplasmic reticulum cochaperone SIL1. SIL1 acts as a nucleotide exchange factor for BiP, which plays a central role in secretory protein folding. SIL1 mutant cells have reduced BiP-assisted protein folding, cannot fulfil their protein needs, and experience chronic activation of the unfolded protein response (UPR). Maladaptive UPR may explain the cerebellar and skeletal muscle degeneration responsible for the ataxia and muscle weakness typical of MSS. However, the cause of other more variable, clinical manifestations, such as mild to severe mental retardation, hypogonadism, short stature, and skeletal deformities, is less clear. To gain insights into the pathogenic mechanisms and/or adaptive responses to SIL1 loss, we carried out cell biological and proteomic investigations in skin fibroblasts derived from a young patient carrying the SIL1 R111X mutation. Despite fibroblasts not being overtly affected in MSS, we found morphological and biochemical changes indicative of UPR activation and altered cell metabolism. All the cell machineries involved in RNA splicing and translation were strongly downregulated, while protein degradation via lysosome-based structures was boosted, consistent with an attempt of the cell to reduce the workload of the endoplasmic reticulum and dispose of misfolded proteins. Cell metabolism was extensively affected as we observed a reduction in lipid synthesis, an increase in beta oxidation, and an enhancement of the tricarboxylic acid cycle, with upregulation of eight of its enzymes. Finally, the catabolic pathways of various amino acids, including valine, leucine, isoleucine, tryptophan, lysine, aspartate, and phenylalanine, were enhanced, while the biosynthetic pathways of arginine, serine, glycine, and cysteine were reduced. These results indicate that, in addition to UPR activation and increased protein degradation, MSS fibroblasts have profound metabolic alterations, which may help them cope with the absence of SIL1.     

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.     

Oxidative stability of polyunsaturated fatty acids: effect of squalene

The propensity of polyunsaturated fatty acids (PUFAs) to undergo oxidation plays an important role in the integrity of biological membrane and lipid containing foods. The ability of squalene (SQ), a naturally occurring dehydrotriterpene present in animal and plant tissues, to protect linoleic, linolenic, arachidonic and docosahexaenoic acids against temperature‐dependent autoxidation and UVA (ultraviolet A, 320‐380 nm) mediated oxidation was assessed. The oxidation of PUFAs was protected in varying degrees, with highest protection observed for linolenic, arachidonic and docosahexaenoic acids. Linoleic acid was less protected. At a molar ratio of 7:1 (PUFA:SQ) the inhibition of the oxidation process was 22% in the presence of linoleic acid and about 50% in presence of the other PUFAs tested. The different protection exerted by SQ against PUFAs with different degrees of unsaturation may be accounted for by the higher stability of octadecadienoic acid hydroperoxide isomers compared with respective PUFA hydroperoxides. Observing mild UVA‐mediated oxidation and the temperature‐dependent autoxidation reactions we found similarities in the oxidation pattern and the protection exerted by SQ. These findings suggest that the reaction of autoxidation is predominant and SQ acts mainly as peroxyl radical scavenger.