Design and Manufacture of Injection Mold

Import 05/08/2014Diplomová práce se zabývá konstrukcí plastové součásti a vstřikovacího nástroje podle současných standardů. V úvodu diplomové práce je shrnuta problematika vstřikování plastů, konstrukční požadavky na výstřiky a vstřikovací formy. Na základě analýz vstřikování a pevnostních výpočtů je zadaný plastový díl upraven a následně vhodně zaformován do vstřikovacího nástroje. Dále je řešena příslušná vstřikovací forma se všemi náležitostmi pro využití v praxi a navrhnut základní technologický postup výroby tvarové dutiny. Práce obsahuje příslušné 3D data a 2D výkresovou dokumentací.This diploma thesis deals with a design of plastic parts and injection mold according to current standards. At the beginning of the thesis are summarized issues of injection molding, design requirements for the molding parts and injection molds. Based on the analysis of injection and finite element method calculations the specific plastic part is modified and then suitably adapted to the injection mold tool. Below this thesis the injection mold with all requirements for practical use is soluted and designed the basic technological process of production of the mold cavity. Thesis includes appropriate 3D data and 2D drawings.340 - Katedra výrobních strojů a konstruovánívýborn

Elucidating DNA binding of dithienylethenes from molecular dynamics and dichroism spectra

DNA binding modes of the stereoisomeric rotamers of two dithenylethene derivatives (DTE1 and DTE2) representing candidate molecular photoswitches of great promise for photopharmacology and nanotechnology have been identified and characterized in terms of their binding energies and electronic circular dichroism (CD) responses. In the open form, two binding modes are identified namely minor-groove binding of the lowest-energy conformer with an anti-parallel arrangement of methyl groups and major-groove double-intercalation of the P-enantiomers of an intermediate-state rotamer. Only the latter binding mode is found to be enantiomerically selective and expected to have an overall negative linear dichroism (LD) as observed in the experiment for DTE1 (Angew. Chem., Int. Ed., 2013, 52, 4393). In the closed form, the most favorable binding mode is found to be minor groove binding. Also this binding mode is found to be enantiomerically selective and for DTE1, it is the M-enantiomer that binds the strongest, showing a positive theoretical signature CD band in the long wavelength region with origin in pyridinium ligands. The theoretical CD spectrum is found to be in good agreement with the experimental one, which provides an indirect evidence for a correct identification of the binding mode in the closed form

Wire Tension Systems on the Ring Fixator

Import 03/08/2012Bakalářská práce se zabývá novým řešením napínání drátu u kruhového fixátoru. V úvodu této práce je zpracována problematika zlomenin a rozdělení fixátorů. Dále jsou zde podrobně popsány hlavní části kruhového fixátoru (prstence a typy upínek) různých výrobců, včetně systémů napínání drátu. V této práci jsou také popsány lékařské požadavky na materiál, jednoduchost konstrukce a snadné dopínání drátů. Na základě těchto požadavků, které jsou kladeny na upínku a napínák drátu, jsou v této práci detailně popsána různá konstrukční řešení, která jsou podložena MKP výpočtem a výkresovou dokumentací.This bachelor thes is delas with a new solution of tension wire circular fixator. The introduction of this thesis analyses the problem of fractures and distribution of fixators. Below this thesis, there are discribed the main parts of a circular fixator (rings and clamp types) from different producers, including wire tensioning systems. In this thesis the medical requirements for materials, simple construction and easy tensioning of the wire are also described here. Based on these requirements placed on the wire clamp and tensor are in these thesis describes various design solutions based on FEM calculation and drawing documentation.340 - Katedra výrobních strojů a konstruovánívýborn

Description moléculaires dans le suivi des propriétés optiques et des activités antioxydantes des polyphénols

Polyphenols are abundantly found in many fruit, vegetables, beverages, etc. and they possess many potential health benefits. Computational methods were thoroughly used through this thesis to rationalize, describe and predict physical chemical properties of flavonolignans and pyranoanthocyanins. Here, we aim at an understanding of polyphenol biological actions at a molecular level. All outcomes from the theoretical computations were discussed with respect to experimental data. The properties related to antioxidant activity of flavonolignans were investigated by density functional theory (DFT) methods. The pH dependence of ultraviolet/visible (UV/Vis) absorption properties of flavonolignans and pyranoanthocyanins were evaluated by time dependent (TD-) DFT methods, and noncovalent interactions were investigated within dispersion-corrected DFT methods. A short overview is also given on interaction of such compounds with biomolecules. Chapter 6 presents yet not published results of several noncovalent pigment: copigment systems. This part of the results serves as a good starting point to search for ‘the best copigment’.Les polyphénols sont abondamment trouvés dans de nombreux fruits, légumes, boissons etc. et ils possèdent de nombreux effets bénéfiques pour la santé. Les méthodes de calcul ont été utilisées dans le cadre de cette thèse pour rationaliser, décrire et prédire les propriétés physiques et chimiques des flavonolignanes et des pyranoanthocyanines pour la compréhension de leurs actions biologiques au niveau moléculaire. Tous les résultats des calculs théoriques ont été discutés par rapport aux données expérimentales. Les propriétés liées à l'activité antioxydante des flavonolignanes ont été étudiées par les méthodes de la théorie de la densité fonctionnelle (DFT). La dépendance au pH des propriétés d'absorption UV/Vis des flavonolignanes et des pyranoanthocyanines ont été évaluée par des méthodes DFT dépendante du temps (TD-), et les interactions non-covalentes ont été étudiées avec les méthodes de DFT incluant la correction de dispersion. Un bref aperçu est également donné sur l'interaction de ces composés avec des biomolécules. Le chapitre 6 présente des résultats non encore publiés de plusieurs systèmes non-covalents pigment: copigment. Cette partie des résultats constitue un bon point de départ pour la recherche du ‘meilleur copigment’

Kinetic Monte Carlo simulations of organic ferroelectrics

Ferroelectrics find broad applications, e.g. in non-volatile memories, but the switching kinetics in real, disordered, materials is still incompletely understood. Here, we develop an electrostatic model to study ferroelectric switching using 3D Monte Carlo simulations. We apply this model to the prototypical small molecular ferroelectric trialkylbenzene-1,3,5-tricarboxamide (BTA) and find good agreement between the Monte Carlo simulations, experiments, and molecular dynamics studies. Since the model lacks any explicit steric effects, we conclude that these are of minor importance. While the material is shown to have a frustrated antiferroelectric ground state, it behaves as a normal ferroelectric under practical conditions due to the large energy barrier for switching that prevents the material from reaching its ground state after poling. We find that field-driven polarization reversal and spontaneous depolarization have orders of magnitude different switching kinetics. For the former, which determines the coercive field and is relevant for data writing, nucleation occurs at the electrodes, whereas for the latter, which governs data retention, nucleation occurs at disorder-induced defects. As a result, by reducing the disorder in the system, the polarization retention time can be increased dramatically while the coercive field remains unchanged.Funding Agencies|Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]; Vetenskapsradet; SeRC (Swedish e-Science Research Center)</p

Ground-State Destabilization by Active-Site Hydrophobicity Controls the Selectivity of a Cofactor- Free Decarboxylase

Bacterial arylmalonate decarboxylase (AMDase) and evolved variants have become a valuable tool with which to access both enantiomers of a broad range of chiral arylaliphatic acids with high optical purity. Yet, the molecular principles responsible for the substrate scope, activity and selectivity of this enzyme are only poorly understood to this day, greatly hampering the predictability and design of improved enzyme variants for specific applications. In this work, empirical valence bond and metadynamics simulations were performed on wild-type AMDase and variants thereof, to obtain a better understanding of the underlying molecular processes determining reaction outcome. Our results clearly reproduce the experimentally observed substrate scope, and support a mechanism driven by ground-state destabilization of the carboxylate group being cleaved by the enzyme. In addition, our results indicate that, in the case of the non-converted or poorly-converted substrates studied in this work, increased solvent exposure of the active site upon binding of these substrates can disturb the vulnerable network of interactions responsible for facilitating the AMDase-catalyzed cleavage of CO2. Finally, our results indicate a switch from preferential cleavage of the pro-(R) to the pro-(S) carboxylate group in the CLG-IPL variant of AMDase for all substrates studied. This appears to be due to the emergence of a new hydrophobic pocket generated by the insertion of the six amino acid substitutions, into which the pro-(S) carboxylate binds. Our results allow insight into the tight interaction network determining AMDase selectivity, which in turn provides guidance for the identification of target residues for future enzyme engineering. </div

Ground-State Destabilization by Active-Site Hydrophobicity Controls the Selectivity of a Cofactor-Free Decarboxylase

Bacterial arylmalonate decarboxylase (AMDase) and evolved variants have become a valuable tool with which to access both enantiomers of a broad range of chiral arylaliphatic acids with high optical purity. Yet, the molecular principles responsible for the substrate scope, activity, and selectivity of this enzyme are only poorly understood to date, greatly hampering the predictability and design of improved enzyme variants for specific applications. In this work, empirical valence bond and metadynamics simulations were performed on wild-type AMDase and variants thereof to obtain a better understanding of the underlying molecular processes determining reaction outcome. Our results clearly reproduce the experimentally observed substrate scope and support a mechanism driven by ground-state destabilization of the carboxylate group being cleaved by the enzyme. In addition, our results indicate that, in the case of the nonconverted or poorly converted substrates studied in this work, increased solvent exposure of the active site upon binding of these substrates can disturb the vulnerable network of interactions responsible for facilitating the AMDase-catalyzed cleavage of CO2. Finally, our results indicate a switch from preferential cleavage of the pro-(R) to the pro-(S) carboxylate group in the CLG-IPL variant of AMDase for all substrates studied. This appears to be due to the emergence of a new hydrophobic pocket generated by the insertion of the six amino acid substitutions, into which the pro-(S) carboxylate binds. Our results allow insight into the tight interaction network determining AMDase selectivity, which in turn provides guidance for the identification of target residues for future enzyme engineering

Loop Dynamics and Enzyme Catalysis in Protein Tyrosine Phosphatases

Protein tyrosine phosphatases (PTPs) play an important role in cellular signalling and have been implicated in human cancers, diabetes, and obesity. Despite shared catalytic mechanisms and transition states for the chemical steps of catalysis, catalytic rates within the PTP family vary over several orders of magnitude. These rate differences have been implied to arise from differing conformational dynamics of the closure of a protein loop, the WPD-loop, which carries a catalytically critical residue. The present work reports computational studies of the human protein tyrosine phosphatase 1B (PTP1B), and YopH from Yersinia pestis, for which NMR has demonstrated a link between both their respective rates of WPD-loop motion and catalysis rates, which differ by an order of magnitude. We have performed detailed structural analysis, both conventional and enhanced sampling simulations of their loop dynamics, as well as empirical valence bond simulations of the chemical step of catalysis. These analyses revealed the key residues and structural features responsible for these differences, as well as the residues and pathways that facilitate allosteric communication in these enzymes. Curiously, our wild-type YopH simulations also identify a catalytically incompetent hyper-open conformation of its WPD-loop, sampled as a rare event, previously only experimentally observed in YopH-based chimeras. The effect of differences within the WPD-loop and its neighbouring loops on the modulation of loop dynamics, as revealed in this work, may provide a facile means for the family of PTP enzymes to respond to environmental changes and regulate their catalytic activities. </p

Manipulating Conformational Dynamics To Repurpose Ancient Proteins for Modern Catalytic Functions

Departamento de Quımíca Física, Facultad de Ciencias, Unidad de Excelencia de Quımíca Aplicada a Biomedicina y Medioambiente (UEQ), Universidad de Granada, 18071 Granada, SpainHuman Frontier Science Program (to J.M.S.-R. and S.C.L.K., Grant No. RGP0041/2017), FEDER-funds/Spanish Ministry of Economy and Competitiveness (to J.M.S.-R. Grant No. BIO2015-66426-R), FEDER Funds/Spanish Ministry of Science, Innovation and Universities (to J.M.S.-R., Grant No. RTI2018-097142-B-100), and FEDER Funds/Junta de Andalucia − Consejerıá de Economıá , Conocimiento, Empresas y Universidad (to V.A.R. Grant No. E.FQM.113.UGR18).Universidad de Granad

Negative piezoelectric effect in an organic supramolecular ferroelectric

The vast majority of ferroelectric materials demonstrate a positive piezoelectric effect. Theoretically, the negative piezoelectric coefficient d33 could be found in certain classes of ferroelectrics, yet in practice, the number of materials showing linear longitudinal contraction with increasing applied field (d33 &lt; 0) is limited to few ferroelectric polymers. Here, we measure a pronounced negative piezoelectric effect in the family of organic ferroelectric small-molecular BTAs (trialkylbenzene-1,3,5-tricarboxamides), which can be tuned by mesogenic tail substitution and structural disorder. While the large- and small-signal strain in highly-ordered thin-film BTA capacitor devices are dominated by intrinsic contributions and originates from piezostriction, rising disorder introduces additional extrinsic factors that boost the large-signal d33 up to â\u88\u9220 pm V-\u88\u921 in short-tailed molecules. Interestingly, homologues with longer mesogenic tails show a large-signal electromechanical response that is dominated by the quadratic Maxwell strain with significant mechanical softening upon polarization switching, whereas the small-signal strain remains piezostrictive. Molecular dynamics and DFT calculations both predict a positive d33 for defect-free BTA stacks. Hence, the measured negative macroscopic d33 is attributed to the presence of structural defects that enable the dimensional effect to dominate the piezoelectric response of BTA thin films