A nonmonotone GRASP

A greedy randomized adaptive search procedure (GRASP) is an itera- tive multistart metaheuristic for difficult combinatorial optimization problems. Each GRASP iteration consists of two phases: a construction phase, in which a feasible solution is produced, and a local search phase, in which a local optimum in the neighborhood of the constructed solution is sought. Repeated applications of the con- struction procedure yields different starting solutions for the local search and the best overall solution is kept as the result. The GRASP local search applies iterative improvement until a locally optimal solution is found. During this phase, starting from the current solution an improving neighbor solution is accepted and considered as the new current solution. In this paper, we propose a variant of the GRASP framework that uses a new “nonmonotone” strategy to explore the neighborhood of the current solu- tion. We formally state the convergence of the nonmonotone local search to a locally optimal solution and illustrate the effectiveness of the resulting Nonmonotone GRASP on three classical hard combinatorial optimization problems: the maximum cut prob- lem (MAX-CUT), the weighted maximum satisfiability problem (MAX-SAT), and the quadratic assignment problem (QAP)

Hybridization of multi-objective deterministic particle swarm with derivative-free local searches

The paper presents a multi-objective derivative-free and deterministic global/local hybrid algorithm for the efficient and effective solution of simulation-based design optimization (SBDO) problems. The objective is to show how the hybridization of two multi-objective derivative-free global and local algorithms achieves better performance than the separate use of the two algorithms in solving specific SBDO problems for hull-form design. The proposed method belongs to the class of memetic algorithms, where the global exploration capability of multi-objective deterministic particle swarm optimization is enriched by exploiting the local search accuracy of a derivative-free multi-objective line-search method. To the authors best knowledge, studies are still limited on memetic, multi-objective, deterministic, derivative-free, and evolutionary algorithms for an effective and efficient solution of SBDO for hull-form design. The proposed formulation manages global and local searches based on the hypervolume metric. The hybridization scheme uses two parameters to control the local search activation and the number of function calls used by the local algorithm. The most promising values of these parameters were identified using forty analytical tests representative of the SBDO problem of interest. The resulting hybrid algorithm was finally applied to two SBDO problems for hull-form design. For both analytical tests and SBDO problems, the hybrid method achieves better performance than its global and local counterparts

A multi-objective DIRECT algorithm for ship hull optimization

The paper is concerned with black-box nonlinear constrained multi-objective optimization problems. Our interest is the definition of a multi-objective deterministic partition-based algorithm. The main target of the proposed algorithm is the solution of a real ship hull optimization problem. To this purpose and in pursuit of an efficient method, we develop an hybrid algorithm by coupling a multi-objective DIRECT-type algorithm with an efficient derivative-free local algorithm. The results obtained on a set of “hard” nonlinear constrained multi-objective test problems show viability of the proposed approach. Results on a hull-form optimization of a high-speed catamaran (sailing in head waves in the North Pacific Ocean) are also presented. In order to consider a real ocean environment, stochastic sea state and speed are taken into account. The problem is formulated as a multi-objective optimization aimed at (i) the reduction of the expected value of the mean total resistance in irregular head waves, at variable speed and (ii) the increase of the ship operability, with respect to a set of motion-related constraints. We show that the hybrid method performs well also on this industrial problem

Neuroprotective potential of isothiocyanates in an in vitro model of neuroinflammation

Isothiocyanates (ITCs), present as glucosinolate precursors in cruciferous vegetables, have shown anti-inflammatory, antioxidant and anticarcinogenic activities. Here, we compared the effects of three different ITCs on ROS production and on the expression of matrix metalloproteinase (MMP)-2 and -9, which represent important pathogenetic factors of various neurological diseases. Primary cultures of rat astrocytes were activated by LPS and simultaneously treated with different doses of Allyl isothiocyanate (AITC), 2-Phenethyl isothiocyanate (PEITC) and 2-Sulforaphane (SFN). Results showed that SFN and PEITC were able to counteract ROS production induced by H2O2. The zymographic analysis of cell culture supernatants evidenced that PEITC and SFN were the most effective inhibitors of MMP-9, whereas, only SFN significantly inhibited MMP-2 activity. PCR analysis showed that all the ITCs used significantly inhibited both MMP-2 and MMP-9 expression. The investigation on the mitogen-activated protein kinase (MAPK) signaling pathway demonstrated that ITCs modulate MMP transcription by inhibition of extracellular-regulated protein kinase (ERK) activity. Results of this study suggest that ITCs could be promising nutraceutical agents for the prevention and complementary treatment of neurological diseases associated with MMP involvement

Status of the Cylindical-GEM project for the KLOE-2 Inner Tracker

The status of the R&D on the Cylindrical-GEM (CGEM) detector foreseen as Inner Tracker for KLOE-2, the upgrade of the KLOE experiment at the DAFNE phi-factory, will be presented. The R&D includes several activities: i) the construction and complete characterization of the full-size CGEM prototype, equipped with 650 microns pitch 1-D longitudinal strips; ii) the study of the 2-D readout with XV patterned strips and operation in magnetic field (up to 1.5T), performed with small planar prototypes in a dedicated test at the H4-SPS beam facility; iii) the characterization of the single-mask GEM technology for the realization of large-area GEM foils.Comment: 4 pages, 10 figures, Presented at Vienna Conference on Instrumentation (Feb 15-20, 2010, Vienna, Austria). Submitted to the Proceeding

Biological variations in a long-term ex situ cultivation: a Mediterranean demosponge as model system

The demosponge Tethya citrina Sarà & Melone was subjected to long-term aquarium farming, considering that several species belonging to this genus are a rich source of useful bioactive metabolites. The rearing method in the present research was mainly based on applying parameters taken from the current literature. The sponge's biological activity was assessed in terms of survival and growth over time; status of filtering apparatus; protein banding profiles. Farmed sponges showed a high survival rate and marked reduction in size. In addition, they were frequently affected by massive production of asexual buds. Histological and ultrastructural observations showed a gradual disorganization of the sponge choanocyte chambers, with a drastic reduction in choanocytes and a progressive increase in spherulous cells. Comparative electrophoretic analysis of the protein profiles of wild and reared specimens showed differences in protein composition and abundance between the tested groups. Such data are consistent with the increase in spherulous cells whose content was markedly electron-dense, a feature stressing the proteinaceous nature of these inclusions. Experimental tank-rearing of Tethya provided promising responses in terms of high survival rate of the species and easy reproduction, though the rearing protocol used led to profound morpho-functional changes in the sponge. This confirms the inadequate state of knowledge on farming techniques for this taxon, while also highlighting potential applications in biotechnology of ex situ breeding techniques, in order to modify the sponges' biological responses

Noninvasive Ultrasound Monitoring of Embryonic and Fetal Development in Chinchilla lanigera to Predict Gestational Age: Preliminary Evaluation of This Species as a Novel Animal Model of Human Pregnancy

Ultrasound is a noninvasive routine method that allows real-time monitoring of fetal development in utero to determine gestational age and to detect congenital anomalies and multiple pregnancies. To date, the developmental biology of Chinchilla lanigera has not yet been characterized. This species has been found to undergo placentation, long gestation, and fetal dimensions similar to those in humans. The aim of this study was to assess the use of high-frequency ultrasound (HFUS) and clinical ultrasound (US) to predict gestational age in chinchillas and evaluate the possibility of this species as a new animal model for the study of human pregnancy. In this study, 35 pregnant females and a total of 74 embryos and fetuses were monitored. Ultrasound examination was feasible in almost all chinchilla subjects. It was possible to monitor the chinchilla embryo with HFUS from embryonic day (E) 15 to 60 and with US from E15 to E115 due to fetus dimensions. The placenta could be visualized and measured with HFUS from E15, but not with US until E30. From E30, the heartbeat became detectable and it was possible to measure fetal biometrics. In the late stages of pregnancy, stomach, eyes, and lenses became visible. Our study demonstrated the importance of employing both techniques while monitoring embryonic and fetal development to obtain an overall and detailed view of all structures and to recognize any malformation at an early stage. Pregnancy in chinchillas can be confirmed as early as the 15th day postmating, and sonographic changes and gestational age are well correlated. The quantitative measurements of fetal and placental growth performed in this study could be useful in setting up a database for comparison with human fetal ultrasounds. We speculate that, in the future, the chinchilla could be used as an animal model for the study of US in human pregnancy

Predictors of Postabsorptive Ghrelin Secretion after Intake of Different Macronutrients

Abstract Context: Release of ghrelin, a gastrointestinal hormone regulating feeding and energy balance, is blunted in obesity, a condition associated with insulin resistance. Objective: The objective was to identify anthropometric and metabolic predictors of postabsorptive ghrelin secretion. Design: We evaluated ghrelin, insulin, glucose, and leptin secretion overnight and after intake of different macronutrients. Subjects: Ten obese subjects (age, 31.8 ± 2.5 yr; body mass index, 43.4 ± 0.8 kg/m2) and six lean subjects (age, 33.5 ± 2.4 yr; body mass index, 21.8 ± 1.4 kg/m2) participated in the study. Main Outcome Measures: The main outcome measures were resting energy expenditure (REE); fat mass; nighttime approximate entropy (ApEn) and synchronicity (cross-ApEn) of ghrelin, insulin, and leptin; insulin sensitivity by homeostatic model approach insulin-sensitivity (HOMA-S%); postabsorptive area under the curve (AUC); and Δ of ghrelin, insulin, glucose, and leptin after carbohydrate-, lipid-, and protein-rich test meals. Results: Nighttime ApEn scores were higher in obese than lean subjects (P < 0.01). Cross-ApEn revealed a synchronicity between ghrelin-insulin, ghrelin-leptin, and insulin-leptin in both groups. Compared with baseline, ghrelin decreased significantly (P < 0.01) in lean and obese subjects after carbohydrates (42.2 vs. 28.5%; P < 0.05), lipids (40.2 vs. 26.2%; P < 0.01), and proteins (42.2 vs. 26.3%; P < 0.01) devoid of between-meal ghrelin differences. Significant associations occurred between nocturnal ghrelin ApEn and insulin (r = 0.53; P < 0.05), postmeal ghrelin AUCs and REE (r = −0.57; P < 0.05), and HOMA-S% (r = 0.52; P < 0.05), postmeal ghrelin Δ and HOMA-S% (r = 0.60; P < 0.05). REE (β = −0.57; P = 0.02) and ghrelin ApEn (β = −0.62; P = 0.01) were predictors of postmeal ghrelin AUC and Δ, respectively. Conclusions: Obesity determined a decreased orderliness of ghrelin secretion and a relative loss of ghrelin-insulin synchrony. Postabsorptive ghrelin secretion decreased significantly both in obese and lean subjects, was related to insulin sensitivity, and was predicted by energy expenditure and hormone pulsatility

Enniatin and Beauvericin Biosynthesis in Fusarium Species: Production Profiles and Structural Determinant Prediction

Citation: Liuzzi, V. C., Mirabelli, V., Cimmarusti, M. T., Haidukowski, M., Leslie, J. F., Logrieco, A. F., . . . Mule, G. (2017). Enniatin and Beauvericin Biosynthesis in Fusarium Species: Production Profiles and Structural Determinant Prediction. Toxins, 9(2), 17. doi:10.3390/toxins9020045Members of the fungal genus Fusarium can produce numerous secondary metabolites, including the nonribosomal mycotoxins beauvericin (BEA) and enniatins (ENNs). Both mycotoxins are synthesized by the multifunctional enzyme enniatin synthetase (ESYN1) that contains both peptide synthetase and S-adenosyl-L-methionine-dependent N-methyltransferase activities. Several Fusarium species can produce ENNs, BEA or both, but the mechanism(s) enabling these differential metabolic profiles is unknown. In this study, we analyzed the primary structure of ESYN1 by sequencing esyn1 transcripts from different Fusarium species. We measured ENNs and BEA production by ultra-performance liquid chromatography coupled with photodiode array and Acquity QDa mass detector (UPLC-PDA-QDa) analyses. We predicted protein structures, compared the predictions by multivariate analysis methods and found a striking correlation between BEA/ENN-producing profiles and ESYN1 three-dimensional structures. Structural differences in the beta strand's Asn789-Ala793 and His797-Asp802 portions of the amino acid adenylation domain can be used to distinguish BEA/ENN-producing Fusarium isolates from those that produce only ENN