Atomistic fracture: QFM vs. MD

In this work we discuss the paradigmatic case of brittle fracture in defective elastic-plastic cubic silicon carbide, by a combination of Quantized Fracture Mechanics and Molecular Dynamics atomistic simulations. Different defect sizes and shapes, or crack-inclusion interactions are considered. Our results show that Quantized Fracture Mechanics is able to effectively incorporate the main lattice-related features, while Molecular Dynamics atomistic simulations do provide the most basic level of understanding of mechanical behaviour of brittle materials.     

Physiological basis of sensitivity to enzymatic browning in ‘lettuce’, ‘escarole’ and ‘rocket salad’ when stored as fresh-cut products

In fresh-cut leafy vegetables, the operation of cutting may stimulate enzymatic browning, with important commercial consequences. In this work, a number of physiological and biochemical parameters, including the activities of key enzymes involved in the metabolism of phenols (such as PAL, PPO, and PODs) and ascorbic acid (ASA), were measured in three species: lettuce (Lactuca sativa var. capitata L.), escarole (Cichorium indivia var. latifolium) and rocket salad (Eruca sativa), upon cold storage as fresh cuts. The first two species are quite sensitive to leaf browning, which does not affect rocket salad.     

Luminescence of heat-treated silicon-based polymers: promising materials for LED applications

A new strategy to obtain transparent, thermally stable, and formable photoluminescent materials for LED applications is presented. Starting from commercially available silicon-based polymers, luminescence properties are developed by means of simple heat treatment. Solid polymethylsilsesquioxane MK (Wacker-Besil^®PMS MK) and liquid poly(ureamethylvinyl)silazane Ceraset (Kion Ceraset^® PUVMS) were thermally treated between 200 and 700 °C for 2 h under Ar atmosphere. Photoluminescence properties were observed in all the samples. The structural rearrangements during thermal annealing were effective in order to red-shift the emission spectra of the untreated polymers to the visible range. The formation of dangling bonds and carbon sp², associated with the annealing procedure and confirmed by means of Electron Paramagnetic Resonance (EPR) spectroscopy and solid state Magic Angle Spinning NMR (MAS-NMR) contribute to the red-shift of the photoluminescence emissions of the polymers. After heat treatment at low temperatures (200, 300, and 400 °C), both the polymers show fluorescence in the UV range. While the polysiloxane reveals white luminescence after annealing at 500 and 600 °C, the polysilazane heat-treated at 500 °C exhibits emission in the blue-green range and is transparent. At higher temperatures the presence of free carbon counteracts the luminescence properties.     

Vitamin D-Related Single Nucleotide Polymorphisms as Risk Biomarker of Cardiovascular Disease

Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels. In addition to environmental risk factors, genetic predisposition increases the risk; this includes alterations in the vitamin D receptor gene (VDR). These alterations play a key role in modifying vitamin D uptake, being able to modify its function and increasing susceptibility to cardiovascular disorders. The aim of this study was to evaluate the association of polymorphisms in the VDR gene and risk of CVD in a Caucasian population. A retrospective case-control study was conducted comprising 246 CVD patients and 246 controls of Caucasian origin from Southern Spain. The genetic polymorphisms BsmI (rs1544410), TaqI (rs731236), ApaI (rs7975232), FokI (rs2228570) and Cdx2 (rs11568820) were determined by means of real-time polymerase chain reaction (PCR) for allelic discrimination using TaqMan^® probes. The logistic regression analysis adjusted for body mass index and diabetes revealed that the TT genotype was associated with a higher risk of CVD in both the genotypic model (p = 0.0430; OR = 2.30; 95% CI = 1.06–5.37; TT vs. CC) and the recessive model (p = 0.0099; OR = 2.71; 95% CI = 1.31–6.07; TT vs. C). Haplotype analysis revealed that the haplotype GAC (p = 0.047; OR = 0.34; 95% CI = 0.12–0.98) was associated with increased risk of CVD. The VDR polymorphisms FokI (rs2228570) was significantly associated with the development of CVD. No influence was observed of the VDR polymorphisms BsmI (rs1544410), TaqI (rs731236), ApaI (rs7975232) and Cdx2 (rs11568820) on the risk of developing CVD in the patients studied.     

In Peripheral Blood Mononuclear Cells Helicobacter pylori Induces the Secretion of Soluble and Exosomal Cytokines Related to Carcinogenesis

Helicobacter pylori promotes the secretion of cytokines that regulate inflammation and carcinogenesis. Immune cells secrete cytokines into the extracellular medium or packaged in exosomes. The objective of this study was to analyze the profile of soluble and exosomal cytokines that were secreted by human peripheral blood mononuclear cells (PBMCs) that were infected with H. pylori and to build a network of interaction between cytokines and cellular proteins. PBMCs were obtained by density gradient centrifugation and infected with H. pylori for 24 h. The infection was verified by immunofluorescence and Western blot for CagA. The exosomes were obtained from culture supernatant by ultracentrifugation and characterized by transmission electron microscopy, particle size analysis, and Western blot for CD9 and CD81. Cytokines were quantified using a multiplex immunoassay in the culture supernatant, intact exosomes, and lysed exosomes. H. pylori adheres to lymphocytes and translocates CagA. In PBMCs, H. pylori induces an increase in the soluble and exosomal IL-1β, IL-6, TNF-α, IL-10, IL-17A, IL-21, and IL-22. The protein–protein interaction (PPI) network shows that soluble and exosomal cytokines interact with proteins that participate in signaling pathways such as NF-κB, MAPK, PI3K-Akt, Jak-STAT, FoxO, and mTOR, that are related to carcinogenesis; moreover, TNF-α had the highest number of interactions. Cytokine-loaded exosomes represent another means of intercellular communication that is activated by H. pylori to stimulate inflammation, carcinogenesis, or cancer progression. Cytokine-loaded exosomes are likely to be associated with extragastrointestinal diseases of inflammatory origin.     

Conjugation of the 9-kDa Isoform of Granulysin with Liposomes Potentiates Its Cytotoxicity

Nine kDa granulysin (GRNLY) is a human cytolytic protein secreted by cytotoxic T lymphocytes (CTL) and NK cells of the immune system whose demonstrated physiological function is the elimination of bacteria and parasites. In previous studies by our group, the anti-tumor capacity of recombinant granulysin was demonstrated, both in vitro and in vivo. In the present work, we developed lipid nanoparticles whose surfaces can bind recombinant granulysin through the formation of a complex of coordination between the histidine tail of the protein and Ni²⁺ provided by a chelating lipid in the liposome composition and termed them LUV-GRNLY, for granulysin-bound large unilamellar vesicles. The objective of this formulation is to increase the granulysin concentration at the site of contact with the target cell and to increase the cytotoxicity of the administered dose. The results obtained in this work indicate that recombinant granulysin binds to the surface of the liposome with high efficiency and that its cytotoxicity is significantly increased when it is in association with liposomes. In addition, it has been demonstrated that the main mechanism of death induced by both granulysin and LUV-GRNLY is apoptosis. Jurkat-shBak cells are resistant to GRNLY and also to LUV-GRNLY, showing that LUV-GRNLY uses the mitochondrial apoptotic pathway to induce cell death. On the other hand, we show that LUV-GRNLY induces the expression of the pro-apoptotic members of the Bcl-2 family Bim and especially PUMA, although it also induced the expression of anti-apoptotic Bcl-x_L. In conclusion, we demonstrate that binding of GRNLY to the surfaces of liposomes clearly augments its cytotoxic potential, with cell death executed mainly by the mitochondrial apoptotic pathway.     

Low-Frequency Harmonic Perturbations Drive Protein Conformational Changes

Protein dynamics has been investigated since almost half a century, as it is believed to constitute the fundamental connection between structure and function. Elastic network models (ENMs) have been widely used to predict protein dynamics, flexibility and the biological mechanism, from which remarkable results have been found regarding the prediction of protein conformational changes. Starting from the knowledge of the reference structure only, these conformational changes have been usually predicted either by looking at the individual mode shapes of vibrations (i.e., by considering the free vibrations of the ENM) or by applying static perturbations to the protein network (i.e., by considering a linear response theory). In this paper, we put together the two previous approaches and evaluate the complete protein response under the application of dynamic perturbations. Harmonic forces with random directions are applied to the protein ENM, which are meant to simulate the single frequency-dependent components of the collisions of the surrounding particles, and the protein response is computed by solving the dynamic equations in the underdamped regime, where mass, viscous damping and elastic stiffness contributions are explicitly taken into account. The obtained motion is investigated both in the coordinate space and in the sub-space of principal components (PCs). The results show that the application of perturbations in the low-frequency range is able to drive the protein conformational change, leading to remarkably high values of direction similarity. Eventually, this suggests that protein conformational change might be triggered by external collisions and favored by the inherent low-frequency dynamics of the protein structure.     

State-feedback implementation of cascade compensators

For general dynamical system Σ and cascade compensator conditions are developed for the existence of a state-feedback law F which when applied to Σ causes the resulting closed-loop system Σ_F to exhibit the same input-output behavior as the cascade connection of Σ with . For a controllable, observable linear system Σ with transfer matrix T_Σ, it is shown that an invertible linear cascade compensator with transfer matrix can be implemented with state feedback if and only if the McMillan degree of T_Σ equal the McMillan degree of .     

Impact of Atorvastatin on Skeletal Muscle Mitochondrial Activity,Locomotion and Axonal Excitability—Evidence from ApoE-/- Mice

The cardiovascular benefit of statins is well established. However, only 20% of high-risk patients remain adequately adherent after 5 years of treatment. Among reasons for discontinuation, statin associated-muscle pain symptoms are the most prevalent. Aim of the present study was to evaluate the impact of high dose atorvastatin on skeletal muscle mitochondrial activity, aerobic and anaerobic exercise, and axonal excitability in a murine model of atherosclerosis. ApoE^-/- mice were fed 12 weeks a high-fat high-cholesterol diet alone or containing atorvastatin (40 mg/Kg/day). Outcomes were the evaluation of muscle mitochondrial functionality, locomotion, grip test, and axonal excitability (compound action potential recording analysis of Aα motor propioceptive, Aβ mechanoceptive and C nociceptive fibres). Atorvastatin led to a reduction in muscle mitochondrial biogenesis and mitochondrial ATP production. It did not affect muscular strength but led to a time-dependent motor impairment. Atorvastatin altered the responsiveness of mechanoceptive and nociceptive fibres, respectively, the Aβ and C fibres. These findings point out to a mild sensitization on mechanical, tactile and pain sensitivity. In conclusion, although the prevalence of muscular side effects from statins may be overestimated, understanding of the underlying mechanisms can help improve the therapeutic approach and reassure adherence in patients needing-to-be-treated.     

Solvable Set/Hyperset Contexts: II. A Goal-Driven Unification Algorithm for the Blended Case

A universe composed by rational ground terms is characterized, both constructively and axiomatically, where the interpreted construct with which designates the operation of adjoining one element to a set, coexists with free Herbrand functors. Ordinary syntactic equivalence must be superseded by a bisimilarity relation ≈, between trees labeled over a signature, that suitably reflects the semantics of with. Membership (definable as “d∈t =_Def (t with d≈t”) meets the non-well-foundedness property characteristic of hyperset theory A goal-driven algorithm for solving the corresponding unification problem is provided, it is proved to be totally correct, and exploited to show that the problem itself is NP-complete. The results are then extended to the treatment of the operator less, designating the one-element removal operation. Applications to the automaton matching and type-finding problems are illustrated. Received: March 4, 1996; revised version: August 24, 1998