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

Optimized Collaborative Brain-Computer Interfaces for Enhancing Face Recognition

The aim of this study is to maximize group decision performance by optimally adapting EEG confidence decoders to the group composition. We train linear support vector machines to estimate the decision confidence of human participants from their EEG activity. We then simulate groups of different size and membership by combining individual decisions using a weighted majority rule. The weights assigned to each participant in the group are chosen solving a small-dimension, mixed, integer linear programming problem, where we maximize the group performance on the training set. We therefore introduce optimized collaborative brain-computer interfaces (BCIs), where the decisions of each team member are weighted according to both the individual neural activity and the group composition. We validate this approach on a face recognition task undertaken by 10 human participants. The results show that optimal collaborative BCIs significantly enhance team performance over other BCIs, while improving fairness within the group. This research paves the way for practical applications of collaborative BCIs to realistic scenarios characterized by stable teams, where optimizing the decision policy of a single group may lead to significant long-term benefits of team dynamics

Improving P300 Speller performance by means of optimization and machine learning

Brain-Computer Interfaces (BCIs) are systems allowing people to interact with the environment bypassing the natural neuromuscular and hormonal outputs of the peripheral nervous system (PNS). These interfaces record a user’s brain activity and translate it into control commands for external devices, thus providing the PNS with additional artificial outputs. In this framework, the BCIs based on the P300 Event-Related Potentials (ERP), which represent the electrical responses recorded from the brain after specific events or stimuli, have proven to be particularly successful and robust. The presence or the absence of a P300 evoked potential within the EEG features is determined through a classification algorithm. Linear classifiers such as stepwise linear discriminant analysis and support vector machine (SVM) are the most used discriminant algorithms for ERPs’ classification. Due to the low signal-to-noise ratio of the EEG signals, multiple stimulation sequences (a.k.a. iterations) are carried out and then averaged before the signals being classified. However, while augmenting the number of iterations improves the Signal-to-Noise Ratio, it also slows down the process. In the early studies, the number of iterations was fixed (no stopping environment), but recently several early stopping strategies have been proposed in the literature to dynamically interrupt the stimulation sequence when a certain criterion is met in order to enhance the communication rate. In this work, we explore how to improve the classification performances in P300 based BCIs by combining optimization and machine learning. First, we propose a new decision function that aims at improving classification performances in terms of accuracy and Information Transfer Rate both in a no stopping and early stopping environment. Then, we propose a new SVM training problem that aims to facilitate the target-detection process. Our approach proves to be effective on several publicly available datasets

The Na+/Ca2+ Exchanger 3 Is Functionally Coupled With the NaV1.6 Voltage-Gated Channel and Promotes an Endoplasmic Reticulum Ca2+ Refilling in a Transgenic Model of Alzheimer’s Disease

The remodelling of neuronal ionic homeostasis by altered channels and transporters is a critical feature of the Alzheimer’s disease (AD) pathogenesis. Different reports converge on the concept that the Na+/Ca2+ exchanger (NCX), as one of the main regulators of Na+ and Ca2+ concentrations and signalling, could exert a neuroprotective role in AD. The activity of NCX has been found to be increased in AD brains, where it seemed to correlate with an increased neuronal survival. Moreover, the enhancement of the NCX3 currents (INCX) in primary neurons treated with the neurotoxic amyloid β 1–42 (Aβ1–42) oligomers prevented the endoplasmic reticulum (ER) stress and neuronal death. The present study has been designed to investigate any possible modulation of the INCX, the functional interaction between NCX and the NaV1.6 channel, and their impact on the Ca2+ homeostasis in a transgenic in vitro model of AD, the primary hippocampal neurons from the Tg2576 mouse, which overproduce the Aβ1–42 peptide. Electrophysiological studies, carried in the presence of siRNA and the isoform-selective NCX inhibitor KB-R7943, showed that the activity of a specific NCX isoform, NCX3, was upregulated in its reverse, Ca2+ influx mode of operation in the Tg2576 neurons. The enhanced NCX activity contributed, in turn, to increase the ER Ca2+ content, without affecting the cytosolic Ca2+ concentrations of the Tg2576 neurons. Interestingly, our experiments have also uncovered a functional coupling between NCX3 and the voltage-gated NaV1.6 channels. In particular, the increased NaV1.6 currents appeared to be responsible for the upregulation of the reverse mode of NCX3, since both TTX and the Streptomyces griseolus antibiotic anisomycin, by reducing the NaV1.6 currents, counteracted the increase of the INCX in the Tg2576 neurons. In agreement, our immunofluorescence analyses revealed that the NCX3/NaV1.6 co-expression was increased in the Tg2576 hippocampal neurons in comparison with the WT neurons. Collectively, these findings indicate that NCX3 might intervene in the Ca2+ remodelling occurring in the Tg2576 primary neurons thus emerging as a molecular target with a neuroprotective potential, and provide a new outcome of the NaV1.6 upregulation related to the modulation of the intracellular Ca2+ concentrations in AD neurons

Rebound effects of NCX3 pharmacological inhibition: A novel strategy to accelerate myelin formation in oligodendrocytes

The Na+/Ca2+ exchanger NCX3 is an important regulator of sodium and calcium homeostasis in oligodendrocyte lineage. To date, no information is available on the effects resulting from prolonged exposure to NCX3 blockers and subsequent drug washout in oligodendroglia. Here, we investigated, by means of biochemical, morphological and functional analyses, the pharmacological effects of the NCX3 inhibitor, the 5–amino-N-butyl-2–(4–ethoxyphenoxy)-benzamide hydrochloride (BED), on NCXs expression and activity, as well as intracellular [Na+]i and [Ca2+]i levels, during treatment and following drug washout both in human MO3.13 oligodendrocytes and rat primary oligodendrocyte precursor cells (OPCs). BED exposure antagonized NCX activity, induced OPCs proliferation and [Na+]i accumulation. By contrast, 2 days of BED washout after 4 days of treatment significantly upregulated low molecular weight NCX3 proteins, reversed NCX activity, and increased intracellular [Ca2+]i. This BED-free effect was accompanied by an upregulation of NCX3 expression in oligodendrocyte processes and accelerated expression of myelin markers in rat primary oligodendrocytes. Collectively, our findings show that the pharmacological inhibition of the NCX3 exchanger with BED blocker maybe followed by a rebound increase in NCX3 expression and reversal activity that accelerate myelin sheet formation in oligodendrocytes. In addition, they indicate that a particular attention should be paid to the use of NCX inhibitors for possible rebound effects, and suggest that further studies will be necessary to investigate whether selective pharmacological modulation of NCX3 exchanger may be exploited to benefit demyelination and remyelination in demyelinating diseases

Exploring the DNA2-PNA heterotriplex formation in targeting the Bcl-2 gene promoter: A structural insight by physico-chemical and microsecond-scale MD investigation

Peptide Nucleic Acids (PNAs) represent a promising tool for gene modulation in anticancer treatment. The uncharged peptidyl backbone and the resistance to chemical and enzymatic degradation make PNAs highly advantageous to form stable hybrid complexes with complementary DNA and RNA strands, providing higher stability than the corresponding natural analogues. Our and other groups’ research has successfully shown that tailored PNA sequences can effectively downregulate the expression of human oncogenes using antigene, antisense, or anti-miRNA approaches. Specifically, we identified a seven bases-long PNA sequence, complementary to the longer loop of the main G-quadruplex structure formed by the bcl2midG4 promoter sequence, capable of downregulating the expression of the antiapoptotic Bcl-2 protein and enhancing the anticancer activity of an oncolytic adenovirus. Here, we extended the length of the PNA probe with the aim of including the double-stranded Bcl-2 promoter among the targets of the PNA probe. Our investigation primarily focused on the structural aspects of the resulting DNA2-PNA heterotriplex that were determined by employing conventional and accelerated microsecond-scale molecular dynamics simulations and chemical-physical analysis. Additionally, we conducted preliminary biological experiments using cytotoxicity assays on human A549 and MDA-MB-436 adenocarcinoma cell lines, employing the oncolytic adenovirus delivery strategy

Transcriptomics and metabolomics integration reveals redox-dependent metabolic rewiring in breast cancer cells

Rewiring glucose metabolism toward aerobic glycolysis provides cancer cells with a rapid generation of pyruvate, ATP, and NADH, while pyruvate oxidation to lactate guarantees refueling of oxidized NAD+ to sustain glycolysis. CtPB2, an NADH-dependent transcriptional co-regulator, has been proposed to work as an NADH sensor, linking metabolism to epigenetic transcriptional reprogramming. By integrating metabolomics and transcriptomics in a triple-negative human breast cancer cell line, we show that genetic and pharmacological down-regulation of CtBP2 strongly reduces cell proliferation by modulating the redox balance, nucleotide synthesis, ROS generation, and scavenging. Our data highlight the critical role of NADH in controlling the oncogene-dependent crosstalk between metabolism and the epigenetically mediated transcriptional program that sustains energetic and anabolic demands in cancer cells

Investigations of the Mars Upper Atmosphere with ExoMars Trace Gas Orbiter

The Martian mesosphere and thermosphere, the region above about 60 km, is not the primary target of the ExoMars 2016 mission but its Trace Gas Orbiter (TGO) can explore it and address many interesting issues, either in-situ during the aerobraking period or remotely during the regular mission. In the aerobraking phase TGO peeks into thermospheric densities and temperatures, in a broad range of latitudes and during a long continuous period. TGO carries two instruments designed for the detection of trace species, NOMAD and ACS, which will use the solar occultation technique. Their regular sounding at the terminator up to very high altitudes in many different molecular bands will represent the first time that an extensive and precise dataset of densities and hopefully temperatures are obtained at those altitudes and local times on Mars. But there are additional capabilities in TGO for studying the upper atmosphere of Mars, and we review them briefly. Our simulations suggest that airglow emissions from the UV to the IR might be observed outside the terminator. If eventually confirmed from orbit, they would supply new information about atmospheric dynamics and variability. However, their optimal exploitation requires a special spacecraft pointing, currently not considered in the regular operations but feasible in our opinion. We discuss the synergy between the TGO instruments, specially the wide spectral range achieved by combining them. We also encourage coordinated operations with other Mars-observing missions capable of supplying simultaneous measurements of its upper atmosphere

Water Vapor Vertical Profiles on Mars in Dust Storms Observed by TGO/NOMAD

It has been suggested that dust storms efficiently transport water vapor from the near‐surface to the middle atmosphere on Mars. Knowledge of the water vapor vertical profile during dust storms is important to understand water escape. During Martian Year 34, two dust storms occurred on Mars: a global dust storm (June to mid‐September 2018) and a regional storm (January 2019). Here we present water vapor vertical profiles in the periods of the two dust storms (Ls = 162–260° and Ls = 298–345°) from the solar occultation measurements by Nadir and Occultation for Mars Discovery (NOMAD) onboard ExoMars Trace Gas Orbiter (TGO). We show a significant increase of water vapor abundance in the middle atmosphere (40–100 km) during the global dust storm. The water enhancement rapidly occurs following the onset of the storm (Ls~190°) and has a peak at the most active period (Ls~200°). Water vapor reaches very high altitudes (up to 100 km) with a volume mixing ratio of ~50 ppm. The water vapor abundance in the middle atmosphere shows high values consistently at 60°S‐60°N at the growth phase of the dust storm (Ls = 195°–220°), and peaks at latitudes greater than 60°S at the decay phase (Ls = 220°–260°). This is explained by the seasonal change of meridional circulation: from equinoctial Hadley circulation (two cells) to the solstitial one (a single pole‐to‐pole cell). We also find a conspicuous increase of water vapor density in the middle atmosphere at the period of the regional dust storm (Ls = 322–327°), in particular at latitudes greater than 60°S