Neurological and Mental Disorders

Mental disorders can result from disruption of neuronal circuitry, damage to the neuronal and non-neuronal cells, altered circuitry in the different regions of the brain and any changes in the permeability of the blood brain barrier. Early identification of these impairments through investigative means could help to improve the outcome for many brain and behaviour disease states.The chapters in this book describe how these abnormalities can lead to neurological and mental diseases such as ADHD (Attention Deficit Hyperactivity Disorder), anxiety disorders, Alzheimer’s disease and personality and eating disorders. Psycho-social traumas, especially during childhood, increase the incidence of amnesia and transient global amnesia, leading to the temporary inability to create new memories.Early detection of these disorders could benefit many complex diseases such as schizophrenia and depression

STABLE ADAPTIVE STRATEGY of HOMO SAPIENS and EVOLUTIONARY RISK of HIGH TECH. Transdisciplinary essay

The co-evolutionary concept of Three-modal stable evolutionary strategy of Homo sapiens is developed. The concept based on the principle of evolutionary complementarity of anthropogenesis: value of evolutionary risk and evolutionary path of human evolution are defined by descriptive (evolutionary efficiency) and creative-teleological (evolutionary correctly) parameters simultaneously, that cannot be instrumental reduced to others ones. Resulting volume of both parameters define the trends of biological, social, cultural and techno-rationalistic human evolution by two gear mechanism ˗ gene-cultural co-evolution and techno- humanitarian balance. The resultant each of them can estimated by the ratio of socio-psychological predispositions of humanization/dehumanization in mentality. Explanatory model and methodology of evaluation of creatively teleological evolutionary risk component of NBIC technological complex is proposed. Integral part of the model is evolutionary semantics (time-varying semantic code, the compliance of the biological, socio-cultural and techno-rationalist adaptive modules of human stable evolutionary strategy)

Investigation of proteins and their modifications using high-resolution mass spectrometry

Advances in mass spectrometry (MS) has allowed for the deep analysis of various proteomes, providing identifications of proteins and their modifications. The true power in modern-day proteomics is the application of MS techniques to address various biological questions, propelling disease research and biochemical understanding of organisms. We have utilized high-resolution mass spectrometry to investigate biological questions leading to a greater knowledge of cellular biology. The transcriptional co-activator with PDZ-binding motif (TAZ), is regulated by reversible phosphorylation. However, sequence analysis suggests many potential uncharacterized sites of TAZ phosphorylation, specifically in regions in close proximity to a critical phosphorylation site making site assignment challenging. Using both targeted and untargeted approaches, we identified novel TAZ phosphorylation sites, using a reaction monitoring scheme to resolve positional phosphoisomers, and determined the biological consequence of a novel site, serine 93, on TAZ localization. Spinal muscular atrophy (SMA) is a motor neuron disease affecting 1 in 10,000 individuals. SMA has been shown to involve the release of extracellular vesicles (EVs), which have been used as a source of biomarkers for disease. We examined the use of EVs as a source of SMA biomarkers. We isolated and quantified \u3e650 proteins from SMA-derived vesicles finding potential biomarkers, one of which was confirmed in patients, suggesting these vesicles coupled with our methods are suitable for SMA biomarker discovery. In the model plant species Arabidopsis thaliana gene expression is heavily regulated through post-translational ubiquitination, however a gap between the number of ubiquitinated substrates identified and genes encoding the ubiquitin machinery exists, suggesting many unidentified modifications exist. The main strategy for studying ubiquitomes across species uses diglycine enrichment followed by MS analysis. We developed a DIA-based MS method coupled with novel sample preparation methods to overcome plant-specific challenges and increase the repository of the Arabidopsis ubiquitome, identifying 160 proteins with over 400 ubiquitination sites. The prevalent Charcot-Marie-Tooth disease can be caused by mutations in the lipid phosphatase MTMR2, a protein critical for regulating endosomal dynamics. MTMR2 is regulated by phosphorylation at serine 58. However, the phosphatase and the alterations in protein-protein interactions occurring with this modification have not been thoroughly investigated. To isolate MTMR2 interacting proteins, we utilized in vivo labeling fusing BirA biotin ligase to MTMR2, followed by MS analysis, identifying a putative interactor, TSSC1. We also provide evidence that MTMR2 itself may be subjected to phosphorylation-dependent degradation. This work utilizes high-resolution MS techniques to link protein regulation and function in a variety of biological and cellular contexts. The techniques presented here can be applied to address the gaps of knowledge in various proteomes and are amenable to user-specific modifications. The techniques here provide a framework for determining disease biomarkers for neurological diseases from EVs, investigating proteome-wide changes through protein modifications, and ultimately link high-resolution analytical mass spectrometry techniques and data to address critical biological events in a robust fashion

Shortest Route at Dynamic Location with Node Combination-Dijkstra Algorithm

Abstract— Online transportation has become a basic requirement of the general public in support of all activities to go to work, school or vacation to the sights. Public transportation services compete to provide the best service so that consumers feel comfortable using the services offered, so that all activities are noticed, one of them is the search for the shortest route in picking the buyer or delivering to the destination. Node Combination method can minimize memory usage and this methode is more optimal when compared to A* and Ant Colony in the shortest route search like Dijkstra algorithm, but can’t store the history node that has been passed. Therefore, using node combination algorithm is very good in searching the shortest distance is not the shortest route. This paper is structured to modify the node combination algorithm to solve the problem of finding the shortest route at the dynamic location obtained from the transport fleet by displaying the nodes that have the shortest distance and will be implemented in the geographic information system in the form of map to facilitate the use of the system. Keywords— Shortest Path, Algorithm Dijkstra, Node Combination, Dynamic Location (key words

Neurochemical and Neuropharmacological Studies on a Range of Novel Psychoactive Substances

Introduction: Over recent decades, there has been an increase in the availability and use of Novel Psychoactive Substances (NPS) all over the world. They include several classes of chemicals that mimic the effects of illicit drugs and have been purposefully introduced into the market to circumvent or undermine the purpose of legal regulation. Currently, there is information lacking on the pharmacology of these substances; however, the increasing number of cases and outbreaks of intoxications/deaths is becoming a cause for deepening concern. Multi-disciplinary research in the fields of biology, chemistry, clinical medicine and web analysis is needed to develop responses against this tidal wave. Aim: The overall aim of this project is to gain insights into pharmacological, neurochemical and molecular properties of selected NPS to provide a reliable background needed for detection, assessment, and management of NPS-related harms. A range of approaches and methodologies was employed and a spectrum of different fields of knowledge has been engaged to gain some understanding into the complex multi-faceted phenomenon of NPS. Methods: Different substances have been selected as targets for the present project according to the clinical pattern of toxicity raised by their worldwide use and the lack of scientific knowledge available about them. The methods employed were: in vitro quantitative autoradiography (to evaluate the binding properties of the novel SCs BB-22, 5F-PB-22, 5F-AKB-48 and STS-135 at the cannabinoid receptor type 1 and N-methyl-D-aspartate receptor; and the binding properties of the synthetic stimulants 5-IT and 2-DPMP at the dopamine transporter in rat brain slices); in vitro Fast Scan Cyclic Voltammetry (to assess the effects of BB-22 on evoked dopamine efflux and dopamine re-uptake half-life in nucleus accumbens brain slices); in vivo microdialysis (to monitor dopamine release in terminal areas of the reward system after acute administration of the synthetic cannabinoids BB-22, 5F-PB-22, 5F-AKB-48 and STS-135; the dieting aid compound 2,4-DNP; the synthetic stimulants 2-DPMP and D2PM in freely moving animals); in silico molecular docking (to investigate the intermolecular interactions of the SCs BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, and other referent compounds, with a homology model of the rodent cannabinoid receptor type 1 (CB1R) and the crystal structure of the human CB1R); and a web-based analysis approach (to analyse the information provided by a range of fora communities on 4,4’-DMAR use, additionally critical reviewing the available evidence-based literature on this topic). Results: Our in vitro quantitative autoradiography studies, confirmed that the index compounds BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, behave as highly potent CB1R ligands able to compete with the radioligand [3H]CP-55,940 in cortical and striatal brain slices. On the other hand, all synthetic cannabinoids tested were unable to compete with the radioligand [3H]MK-801 in the same cerebral areas, rejecting the hypothesis of their potential binding to the N-methyl-D-aspartate receptor (NMDAR) at all concentrations investigated. Consistent with previous in vitro studies, 5-IT and 2-DPMP behaved as highly potent dopamine transporter (DAT) ligands able to compete with the radioligand [125 I]RTI-121 in a concentration-dependent way in the Caudate Putamen (CPu) and Nucleus Accumbens (NAc) brain slices. Notably, 2-DPMP was able to displace the radioligand in both cerebral regions, starting from lower concentrations compared to 5-IT. In vitro Fast Scan Cyclic Voltammetry findings demonstrated that local application of the synthetic cannabinoid BB-22 in brain slices, was unable to change evoked dopamine efflux and dopamine reuptake time-constant in the NAc shell at any doses tested. The results obtained would suggest the relative contributions of complex neuronal circuits, either within or outside the NAc, whose modulation would interfere with the interactions between BB-22 and dopaminergic neurons and represent critical pathways accounting for some of the rewarding properties of BB-22 exposure. In vivo microdialysis outcomes suggested that all SCs tested could increase dopamine release in the NAc shell at specific doses, while no changes in dopamine output were observed in other areas of the reward system, namely NAc core and medial prefrontal cortex (mPFCx) after BB-22 administration. These outcomes provided a circumstantial pre-clinical evidence for a greater putative abuse liability of SCs compared to the natural compound found in cannabis (Δ9‐THC). Furthermore, the acute treatment with 2,4-DNP did not cause any change in dopamine release in the NAc shell and CPu rejecting the hypothesis of psychoactivity of this substance at the dose tested. On the other hand, the synthetic stimulant 2-DPMP elicited a comparable increase of dopamine (DA) release in the NAc shell and CPu at the higher doses tested, while D2PM caused a selective increase of DA release in the NAc shell, providing a circumstantial preclinical evidence for a putative abuse liability of this compound at the highest dose assessed. The in silico molecular docking studies demonstrated that the SCs BB-22, 5F-PB-22, 5F-AKB-48 and STS-135 interact with CB1 receptor residues that, according to previous mutation and computational studies, are considered crucial for synthetic cannabinoid binding recognition. Additionally, they share some interacting residues with other aminoalkylindole derivatives (e.g. WIN-55,212-2). The web-based analysis focused on 4,4’-DMAR, suggested that fora members co-operate in exchanging an extensive body of knowledge about this drug, and the recurring topics of discussion include: routes of administration and dosages; desired and undesired effects; comparison and association with other drugs and medications; overall impression; provision of harm reduction advice. This approach has been useful to better understand some of the clinical and psychopharmacological issues pertaining to 4,4’-DMAR. Conclusions: Overall, these studies provided new pharmacological, neurochemical and molecular knowledge on a range of Novel Psychoactive Substances essential for identifying potential therapeutical approaches against their use/abuse. The novelty of this project lies in the adoption of a multi-disciplinary approach involving a range of methodologies from different areas of expertise (neurobiology, pharmacology, chemistry, netnography) all integrated to clarify some aspects of the index NPS, which were not yet available in the current literature. Additional studies are needed to better explain short and long-term effects of the index NPS, their abuse potential, and their interactions with other drugs of abuse

Advanced Modeling and Research in Hybrid Microgrid Control and Optimization

This book presents the latest solutions in fuel cell (FC) and renewable energy implementation in mobile and stationary applications. The implementation of advanced energy management and optimization strategies are detailed for fuel cell and renewable microgrids, and for the multi-FC stack architecture of FC/electric vehicles to enhance the reliability of these systems and to reduce the costs related to energy production and maintenance. Cyber-security methods based on blockchain technology to increase the resilience of FC renewable hybrid microgrids are also presented. Therefore, this book is for all readers interested in these challenging directions of research

A Review of Resonant Converter Control Techniques and The Performances

paper first discusses each control technique and then gives experimental results and/or performance to highlights their merits. The resonant converter used as a case study is not specified to just single topology instead it used few topologies such as series-parallel resonant converter (SPRC), LCC resonant converter and parallel resonant converter (PRC). On the other hand, the control techniques presented in this paper are self-sustained phase shift modulation (SSPSM) control, self-oscillating power factor control, magnetic control and the H-∞ robust control technique

A Review of Resonant Converter Control Techniques and The Performances

paper first discusses each control technique and then gives experimental results and/or performance to highlights their merits. The resonant converter used as a case study is not specified to just single topology instead it used few topologies such as series-parallel resonant converter (SPRC), LCC resonant converter and parallel resonant converter (PRC). On the other hand, the control techniques presented in this paper are self-sustained phase shift modulation (SSPSM) control, self-oscillating power factor control, magnetic control and the H-∞ robust control technique

OBSERVER-BASED-CONTROLLER FOR INVERTED PENDULUM MODEL

This paper presents a state space control technique for inverted pendulum system. The system is a common classical control problem that has been widely used to test multiple control algorithms because of its nonlinear and unstable behavior. Full state feedback based on pole placement and optimal control is applied to the inverted pendulum system to achieve desired design specification which are 4 seconds settling time and 5% overshoot. The simulation and optimization of the full state feedback controller based on pole placement and optimal control techniques as well as the performance comparison between these techniques is described comprehensively. The comparison is made to choose the most suitable technique for the system that have the best trade-off between settling time and overshoot. Besides that, the observer design is analyzed to see the effect of pole location and noise present in the system