Application of molecular simulation techniques to the design of nanosystems

Nanotechnology is a multidisciplinary branch of science and technology that involves a widerange of different fields such as chemistry, materials science, physics or chemical engineeringwhose goal is the production of new functional materials and devicesthrough the control of their organization at the atomic and molecular scale.Nanotechnology has jumped from research laboratories to our daily life and today all theprogresses made in this field have been translated into direct applications in different fields being electronics and computer science and biomedicine, where the most striking advances have beendone.What differences nanotechnology from traditional chemistry and physics can be summarized inthree points: (i) Analysis and control of the matterat the atomic and molecular level focusing in individual atoms; (ii) the appearance of novel physical properties because of the nanoscopicdimensions; (iii) the possibility of generating new complex functional systems with novelproperties.Modeling and theory are becoming vital to designing and improving nanodevices. The intrinsicnature of nano and supramolecular scale that involves tens, hundreds and thousands of atomsmakes computational chemistry the perfect ally to design new devices and predict their properties. Computational chemistry provides the perfect tools to describe the electronic structureand the dynamic behavior, as well as the properties derived from them, through quantummechanics and classical mechanics formalisms.The suitability of such techniques in the design and improvement of nanodevices as well as theprediction of their properties is clearly proven throughout the four blocks in which this thesis isdivided:· Nanotubes based on natural peptide sequencesNanotubes have gained extensive interest because of their applicability in different fieldsranging from medicine to electronics. Among nanotubes, those based on natural peptidesequences taken from some natural proteins with a tubular or fibrillar motif are gaining abroad attention because of their high biocompatibility, the possibility of adding functionalitiesby tuning them and their potentiality to self-assemble. The enhancement of the ability to retain the tubular geometry of such structures can be achieved by substituting targeted amino acids located in the more flexible parts of the nanoconstruct by synthetic amino acids withlow conformational flexibility providing a larger rigidity to the overall structure.· Dendronized polymersDendronized polymers are a specific kind of macromolecule structure that consists of a linearpolymeric backbone where dendritic units are attached regularly leading to a highly branchedthree-dimensional architecture. This fact provides dendronized polymers the peculiarity of the coexistence within the same macromolecule of three topological regions: (i) the internalbackbone; (ii) the dendron region around the backbone and (iii) the external surface. Thesemolecules have a wide range of applications in different fields such as biomedical engineering, host-guest chemistry or catalysis.· Theoretical study of ð-conjugated systemsConducting polymers are polymers bearing a characteristic polyconjugated nature which makethem electronic conductors. In particular thiophene-based conducting polymers have been widely studied because of their electric and nonlinear optical properties, excellent environmentalstability and relatively low cost of production. Due to the crucial role played by the electronicstructure of these systems in their relevant properties, a good knowledge of it is a key factor todesign and improve new conducting polymers. To achieve this goal QM calculations suitperfectly to get accurate estimates of such properties.· Molecular actuators and sensors based on conducting polymersBoth experimental and computational research in nanoactuators and nanosensors are widelyreported in the literature. Among them, those based in conducting polymers are flourishingbecause of their great transport properties, electrical conductivity or rate of energy migrationwhich provide amplified sensitivity in nanosensors and a rapid response in nanoactuators. In thissense electron-rich thiophene-based oligomers and polymers combined with versatilecalix[4]arenes units are presented in the present thesis. Calix[4]arenes are synthetic macrocyclic molecules consisting of four phenol or anisole rings connected via methylene bridges that canhost different guest molecules leading to conformational rearrangement of the whole device making it useful to be employed as a sensor or actuator

Фінансовий облік. Методичні рекомендації до виконання курсової роботи з дисципліни для студентів денної та заочної форм навчання напряму підготовки 6.030509 Облік і аудит

Містять тематику курсових робіт. Супроводжуються методичними порадами до виконання, оформлення, захисту залікових робіт і досліджень. Призначено для організації самостійної роботи студентів денної та заочної форм навчання напряму 6.030509 Облік і аудит з виконання курсової роботи на основі використання ними теоретичних і практичних знань, навичок та вмінь, отриманих під час вивчення дисциплін «Фінансовий облік 1» та «Фінансовий облік 2». Орієнтовано на активізацію виконавчого етапу навчальної діяльності студентів та на формування в студентів практичних професійних навичок і вмінь, необхідних для подальшого засвоєння навчальних дисциплін професійно-практичного циклу

OLIMPO, An Ad-Hoc Wireless Sensor Network Simulator for Public Utilities Applications

This paper introduces OLIMPO, an useful simulation tool for researchers who are developing wireless sensor communication protocols. OLIMPO is a discreteevent simulator design to be easily recon gured by the user, providing a way to design, develop and test communication protocols. In particular, we have designed a self-organizing wireless sensor network for low data rate. Our premise is that, due to their inherent spread location over large areas, wireless sensor networks are well-suited for SCADA applications, which require relatively simple control and monitoring. To show the facilities of our simulator, we have studied our network protocol with OLIMPO, developing several simulations. The purpose of these simulations is to demonstrate, quantitatively, the capability of our network to support this kind of applications

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Pre-mRNA splicing takes place in a large ribonucleoprotein complex, the spliceosome, which contains five small nuclear ribonucleoprotein complexes (snRNPs) and over 100 protein factors. There are two types of introns, the major- and the minor-type, that are excised by two different spliceosomes, assembled by two distinct sets of snRNPs: U1, U2, U4, and U6 snRNPs are required for splicing of the major-type introns; U11, U12, U4atac, and U6atac are their corresponding counterparts, involved in minor-type intron splicing. U5 snRNP is common for both spliceosomes. U4 and U6 snRNAs enter the spliceosome in the form of the U4/U6.U5 tri-snRNP, in which they are extensively base-paired. After splicing, U4 and U6 are released as singular snRNPs. In order to restore the tri-snRNP that can participate in another round of splicing, the U4/U6 hybrid must be recycled. The Prp24 protein in the yeast system, and its distant human homologue p110 have been identified as U4/U6 recycling factors and as specific protein components of U6 and U4/U6 snRNPs. This work focuses on the recycling the minor spliceosome and of the minor spliceosomal U4atac/U6atac snRNP. Using a recycling assay coupled to splicing in vitro, p110 was demonstrated to function also as U4atac/U6atac recycling factor. p110 was detected in U6atac snRNP. In contrast to the major U4/U6, however, it is associated only at background levels with U4atac/U6atac snRNP. Interestingly, U4/U6 and U4atac/U6atac hybrids can be also disrupted independently of splicing in vitro. This process may provide a mechanism to control splicing rates in vivo. The sequence elements of U6 and U6atac snRNA, required for interaction with p110 were identified: U6 nucleotides 38 to 57, and U6atac nucleotides 10 to 30 are sufficient for p110 binding. These regions are the most highly conserved between U6 and U6atac. Finally, singular U6 snRNP was purified from HeLa S100 extract. It contained a novel protein, p85 (cDNA GenBank accession AK001239), identified by mass-spectrometric analysis. p85 localizes to the nucleoplasm, and associates not only with U6, but also with U2 snRNA, and 5S and 5.8S rRNAs. This protein is weakly similar to the yeast rRNA processing factor NOP4, which implicates a function of p85 in maturation of U2 and U6 snRNAs.mRNA-Spleißen findet in einem großen Ribonukleoproteinkomplex (RNP) statt, dem Spleißosom, das sich aus 5 kleinen nukleären RNPs (snRNPs) und über 100 Proteinfaktoren zusammensetzt. Es gibt zwei Klassen von Introns, die sogenannten major- und minor-Introns, die von zwei verschiedenen Spleißosomen prozessiert werden. Diese enthalten unterschiedliche Gruppen von snRNPs: U1, U2, U4 und U6 snRNPs werden für das Spleißen von major-Introns benötigt; U11, U12, U4atac und U6atac bilden die funktionsanalogen snRNPs, welche für das Spleissen von minor-Introns essentiell sind. Der U5 snRNP dagegen kommt in beiden Spleissosom-Formen vor. Die U4 und U6 snRNAs werden in das Spleißosom in Form des U4/U6.U5 tri-snRNPs integriert, in welchem sie eine ausgedehnte Basenpaarung aufweisen. Nach Ablauf der Spleissreaktion werden U4 und U6 separat voneinander freigesetzt. Um daraus den tri-snRNP für weitere Runden der Spleißreaktion zu bilden, muß zunächst der U4/U6-Hybrid durch eine Recycling-Reaktion wiederhergestellt werden. Im Hefesystem wurde das Prp24-Protein, im Humansystem dessen verwandtes Protein p110 als U4/U6-Recyclingfaktor identifiziert und als spezifische Proteinkomponente der U6 und U4/U6 snRNPs. Diese Arbeit konzentriert sich auf das Recycling der U4atac und U6atac snRNPs. Mit Hilfe eines mit der Spleissreaktion gekoppelten in vitro-Assays konnte gezeigt werden, daß p110 auch als U4atac/U6atac Recyclingfaktor wirkt. Das p110-Protein wurde im U6atac snRNP nachgewiesen; im Gegensatz zum normalen U4/U6 snRNP ist p110 nur minimal mit dem U4atac/U6atac snRNP assoziiert. Interessanterweise können die U4/U6- und U4atac/U6atac-Hybride auch unabhängig von der in vitro-Spleissreaktion gespalten werden. Dieser Prozeß stellt in vivo möglicherweise einen Kontrollmechanismus der Spleißreaktion dar. Die für die p110-Interaktion notwendigen Sequenzelemente der U6 und U6atac snRNAs wurden kartiert: p110 benötigt Positionen 38-57 in U6 bzw. 10-30 in U6atac. Diese Bereiche sind zwischen den U6 und U6atac snRNAs am stärksten konserviert. Der singuläre U6 snRNP wurde außerdem biochemisch aus HeLa S100-Extrakt gereinigt. Als eine neue Komponente wurde ein Protein, p85, mittels Massenspektrometrie identifiziert (cDNA GenBank accession AK001239). Diese Protein befindet sich im Nukleoplasma und liegt nicht nur mit U6 snRNA gebunden vor, sondern auch mit U2 sowie 5S und 5.8S ribosomaler RNA. p85 zeigt eine geringe Ähnlichkeit mit dem an der ribosomalen RNA-Prozessierung beteiligten NOP4-Faktor aus der Hefe, was eine Funktion von p85 bei der Reifung der U2 und U6 snRNAs nahelegt

A framework to secure the development and auditing of SSL pinning in mobile applications: The case of android devices

Article number 1136The use of mobile devices has undergone rapid growth in recent years. However, on some occasions, security has been neglected when developing applications. SSL/TLS has been used for years to secure communications although it is not a vulnerability-free protocol. One of the most common vulnerabilities is SSL pinning bypassing. This paper first describes some security controls to help protect against SSL pinning bypassing. Subsequently, some existing methods for bypassing are presented and two new methods are defined. We performed some experiments to check the use of security controls in widely used applications, and applied SSL pinning bypassing methods. Finally, we created an applicability framework, relating the implemented security controls and the methods that are applicable. This framework provides a guideline for pentesters and app developers.Ministerio de Ciencia y Tecnología (España) RTI2018-094283-B-C3

Automatic modeling of dynamic drug-hERG channel interactions using three voltage protocols and machine learning techniques: A simulation study

[EN] Background: Assessment of drug cardiac safety is critical in the development of new compounds and is commonly addressed by evaluating the half-maximal blocking concentration of the potassium human ether-à-go-go related gene (hERG) channels. However, recent works have evidenced that the modelling of drug-binding dynamics to hERG can help to improve early cardiac safety assessment. Our goal is to de- velop a methodology to automatically generate Markovian models of the drug-hERG channel interactions. Methods: The training and the test sets consisted of 20800 and 5200 virtual drugs, respectively, dis- tributed into 104 groups with different affinities and kinetics to the conformational states of the chan- nel. In our system, drugs may bind to any state (individually or simultaneously), with different degrees of preference for a conformational state and the change of the conformational state of the drug bound channels may be restricted or allowed. To model such a wide range of possibilities, 12 Markovian chains are considered. Our approach uses the response of the drugs to our three previously developed voltage clamp protocols, which enhance the differences in the probabilities of occupying a certain conformational state of the channel (open, closed and inactivated). The computing tool is comprised of a classifier and a parameter optimizer and uses linear interpolation, support vector machines and a simplex method for function minimization. Results: We propose a novel methodology that automatically generates dynamic drug models using Markov model formulations and that elucidates the states where the drug binds and unbinds and the preferential binding state using data obtained from simple voltage clamp protocols that captures the preferential state-dependent binding properties, the relative affinities, trapping and non-trapping dynam- ics and the onset of I Kr block. Overall, the tool correctly predicted the class of 92.04% of the drugs and the model provided by the tool accurately fitted the response of the target compound, the mean accu- racy being 97.53%. Moreover, generation of the dynamic model of an I Kr blocker from its response to our voltage clamp protocols usually takes less than an hour on a common desktop computer. Conclusion: Our methodology could be very useful to model and simulate dynamic drug¿hERG channel interactions. It would contribute to the improvement of the preclinical assessment of the proarrhythmic risk of drugs that inhibit I Kr and the efficacy of antiarrhythmic I Kr blockers.This work was the Spanish Ministerio de Ciencia, Innovacion y Universidades [grant "Formacion de Profesorado Universitario" FPU19/02200; grant PID2019-104356RB-C41 funded by MCIN/AEI/10.13039/50110 0 011033 ]; the European Union's Horizon 2020 research and innovation program [grant agreement No 101016496 (SimCardioTest)]; and the Direccion General de Politica Cientifica de la Generalitat Valenciana [grant PROMETEO/2020/043]. Patenting of the proposed system/software is under considerationEscobar-Ropero, F.; Gomis-Tena Dolz, J.; Saiz Rodríguez, FJ.; Romero Pérez, L. (2022). Automatic modeling of dynamic drug-hERG channel interactions using three voltage protocols and machine learning techniques: A simulation study. Computer Methods and Programs in Biomedicine. 226:1-10. https://doi.org/10.1016/j.cmpb.2022.10714811022

OLIMPO, an ad-hoc wireless sensor network simulator for optimal scada-applications

This paper introduces OLIMPO, an useful simulation tool for researchers who are developing wireless sensor communication protocols. OLIMPO is a discrete-event simulator design to be easily recon gured by the user, providing a way to design, develop and test communication protocols. In particular, we have designed a self-organizing wireless sensor network for low data rate. Our premise is that, due to their inherent spread location over large areas, wireless sensor networks are well-suited for SCADA applications, which require relatively simple control and monitoring. To show the facilities of our simulator, we have studied our network protocol with OLIMPO, developing several simulations. The purpose of these simulations is to demonstrate, quantitatively, the capability of our network to support this kind of applications

A Hybrid Intelligent Multiagent System for the Remote Control of Solar Farms

This paper describes a multiagent architecture integrated system designed to supervise infrastructures in solar farms. The system enables monitoring the environment by means of sensor networks that are in charge of collecting data. It is designed using a hybrid model composed of an inference engine and an ontology. The former makes the system intelligent, while the latter structures knowledge. We have also developed a tool to configure and use the multiagent system in a simple and intuitive way

Semi-classical treatment of proton-neutron monopole interaction

We apply a time dependent variational method to a many-body Hamiltonian consisting of a spherical shelf model term, a proton-proton and neutron-neutron pairing interaction and a monopole particle-hole and particle-particle proton-neutron interaction. The variational state is a generalized BCS state where all T = 1 Cooper pairs with T-z = 0, +/- 1 are included. Stationary solutions correspond to generalized BCS equations and define the static ground state. The linearized equations of motion are of RPA type and describe small oscillations of the nuclear system around the static ground state. Numerical application is made for a one level case. In contrast to previous treatments, the proton-neutron particle-particle interaction is included first in the mean field equations, defining the quasiparticle approximation, and then the residual interaction is taken into account by the RPA approach. In this way one obtains a noncollapsing RPA ground state.Peer reviewe