Oxidation and pyrolysis of methane and methyl formate in a plug flow reactor: computational and experimenal studies

Biodiesel represents a possible substitute to the fossil fuels; for this reason a good comprehension of the kinetics involved is important. Due to the complexity of the biodiesel mixture a common practice is the use of surrogate molecules to study its reactivity. In this work are presented the experimental and computational results obtained for the oxidation and pyrolysis of methane and methyl formate conducted in a plug flow reactor. The work was divided into two parts: the first one was the setup assembly whilst, in the second one, was realized a comparison between the experimental and model results; these last was obtained using models available in literature. It was started studying the methane since, a validate model was available, in this way was possible to verify the reliability of the experimental results. After this first study the attention was focused on the methyl formate investigation. All the analysis were conducted at different temperatures, pressures and, for the oxidation, at different equivalence ratios. The results shown that, a good comprehension of the kinetics is reach but efforts are necessary to better evaluate kinetics parameters such as activation energy. The results even point out that the realized setup is adapt to study the oxidation and pyrolysis and, for this reason, it will be employed to study a longer chain esters with the aim to better understand the kinetic of the molecules that are part of the biodiesel mixture.

Computational strategies to include protein flexibility in Ligand Docking and Virtual Screening

The dynamic character of proteins strongly influences biomolecular recognition mechanisms. With the development of the main models of ligand recognition (lock-and-key, induced fit, conformational selection theories), the role of protein plasticity has become increasingly relevant. In particular, major structural changes concerning large deviations of protein backbones, and slight movements such as side chain rotations are now carefully considered in drug discovery and development. It is of great interest to identify multiple protein conformations as preliminary step in a screening campaign. Protein flexibility has been widely investigated, in terms of both local and global motions, in two diverse biological systems. On one side, Replica Exchange Molecular Dynamics has been exploited as enhanced sampling method to collect multiple conformations of Lactate Dehydrogenase A (LDHA), an emerging anticancer target. The aim of this project was the development of an Ensemble-based Virtual Screening protocol, in order to find novel potent inhibitors. On the other side, a preliminary study concerning the local flexibility of Opioid Receptors has been carried out through ALiBERO approach, an iterative method based on Elastic Network-Normal Mode Analysis and Monte Carlo sampling. Comparison of the Virtual Screening performances by using single or multiple conformations confirmed that the inclusion of protein flexibility in screening protocols has a positive effect on the probability to early recognize novel or known active compounds.

Computational insight into materials properties

The aim of the work was to explore the practical applicability of molecular dynamics at different length and time scales. From nanoparticles system over colloids and polymers to biological systems like membranes and finally living cells, a broad range of materials was considered from a theoretical standpoint. In this dissertation five chemistry-related problem are addressed by means of theoretical and computational methods. The main results can be outlined as follows. (1) A systematic study of the effect of the concentration, chain length, and charge of surfactants on fullerene aggregation is presented. The long-discussed problem of the location of C60 in micelles was addressed and fullerenes were found in the hydrophobic region of the micelles. (2) The interactions between graphene sheet of increasing size and phospholipid membrane are quantitatively investigated. (3) A model was proposed to study structure, stability, and dynamics of MoS2, a material well-known for its tribological properties. The telescopic movement of nested nanotubes and the sliding of MoS2 layers is simulated. (4) A mathematical model to gain understaning of the coupled diffusion-swelling process in poly(lactic-co-glycolic acid), PLGA, was proposed. (5) A soft matter cell model is developed to explore the interaction of living cell with artificial surfaces. The effect of the surface properties on the adhesion dynamics of cells are discussed.

A 2-dimensional computational model to analyze the effects of cellular heterogeinity on cardiac pacemaking

The mechanical action of the heart is made possible in response to electrical events that involve the cardiac cells, a property that classifies the heart tissue between the excitable tissues. At the cellular level, the electrical event is the signal that triggers the mechanical contraction, inducing a transient increase in intracellular calcium which, in turn, carries the message of contraction to the contractile proteins of the cell. The primary goal of my project was to implement in CUDA (Compute Unified Device Architecture, an hardware architecture for parallel processing created by NVIDIA) a tissue model of the rabbit sinoatrial node to evaluate the heterogeneity of its structure and how that variability influences the behavior of the cells. In particular, each cell has an intrinsic discharge frequency, thus different from that of every other cell of the tissue and it is interesting to study the process of synchronization of the cells and look at the value of the last discharge frequency if they synchronized.

Synthesis and dynamic study of atropisomeric compounds containing boron-carbon bond

In this thesis we studied the stereodynamic behavior of 1,2-azaborines variously substituted on boron (7a, 7b, 13). Depending on the hindrance of the asymmetric aryl substituent the resulting conformations could be stereolabile or configurationally stable. Through dynamic NMR and lineshape simulation, the energy rotational barriers of the different conformers are obtained. When the barrier is higher than 22-23 kcal/mol stable atropisomers that are fisically separable could be obtained (case of compound 13) and the free activation energy barrier is determinable by kinetic analysis. Absolute configuration of two atropisomers were assigned by comparison between computational calculations and experimental ECD. Isosteric compound 21 is then synthesized in order to compare the rotational barrier around B-Caryl with the one around Cnaphth-Caryl bond.

Mesh-based vs. Image-based Statistical Appearance Model of the Human Femur: a Preliminary Comparison Study for the Creation of Finite Element Meshes

Statistical models have been recently introduced in computational orthopaedics to investigate the bone mechanical properties across several populations. A fundamental aspect for the construction of statistical models concerns the establishment of accurate anatomical correspondences among the objects of the training dataset. Various methods have been proposed to solve this problem such as mesh morphing or image registration algorithms. The objective of this study is to compare a mesh-based and an image-based statistical appearance model approaches for the creation of nite element(FE) meshes. A computer tomography (CT) dataset of 157 human left femurs was used for the comparison. For each approach, 30 finite element meshes were generated with the models. The quality of the obtained FE meshes was evaluated in terms of volume, size and shape of the elements. Results showed that the quality of the meshes obtained with the image-based approach was higher than the quality of the mesh-based approach. Future studies are required to evaluate the impact of this finding on the final mechanical simulations.

Semiempirical Study of the Bergman Reaction: Towards a Computationally Efficient and Accurate Method for Modeling Enediyne Anticancer Antibiotics

Over the past 7 years, the enediyne anticancer antibiotics have been widely studied due to their DNA cleaving ability. The focus of these antibiotics, represented by kedarcidin chromophore, neocarzinostatin chromophore, calicheamicin, esperamicin A, and dynemicin A, is on the enediyne moiety contained within each of these antibiotics. In its inactive form, the moiety is benign to its environment. Upon suitable activation, the system undergoes a Bergman cycloaromatization proceeding through a 1,4-dehydrobenzene diradical intermediate. It is this diradical intermediate that is thought to cleave double-stranded dna through hydrogen atom abstraction. Semiempirical, semiempiricalci, Hartree–Fock ab initio, and mp2 electron correlation methods have been used to investigate the inactive hex-3-ene-1,5-diyne reactant, the 1,4-dehydrobenzene diradical, and a transition state structure of the Bergman reaction. Geometries calculated with different basis sets and by semiempirical methods have been used for single-point calculations using electron correlation methods. These results are compared with the best experimental and theoretical results reported in the literature. Implications of these results for computational studies of the enediyne anticancer antibiotics are discussed.

Au@Hg nanoalloy formation through direct amalgamation: Structural, spectroscopic, and computational evidence for slow nanoscale diffusion

Dynamic core-shell nanoparticles have received increasing attention in recent years. This paper presents a detailed study of Au-Hg nanoalloys, whose composing elements show a large difference in cohesive energy. A simple method to prepare Au@Hg particles with precise control over the composition up to 15 atom% mercury is introduced, based on reacting a citrate stabilized gold sol with elemental mercury. Transmission electron microscopy shows an increase of particle size with increasing mercury content and, together with X-ray powder diffraction, points towards the presence of a core-shell structure with a gold core surrounded by an Au-Hg solid solution layer. The amalgamation process is described by pseudo-zero-order reaction kinetics, which indicates slow dissolution of mercury in water as the rate determining step, followed by fast scavenging by nanoparticles in solution. Once adsorbed at the surface, slow diffusion of Hg into the particle lattice occurs, to a depth of ca. 3 nm, independent of Hg concentration. Discrete dipole approximation calculations relate the UV-vis spectra to the microscopic details of the nanoalloy structure. Segregation energies and metal distribution in the nanoalloys were modeled by density functional theory calculations. The results indicate slow metal interdiffusion at the nanoscale, which has important implications for synthetic methods aimed at core-shell particles.

A Computational Analysis of the Collision-Induced Dissociation Mechanisms of the Dipeptide Glycine-Serine Under Mass Spectrometry

Collision-induced dissociation (CID) of peptides using tandem mass spectrometry (MS) has been used to determine the identity of peptides and other large biological molecules. Mass spectrometry (MS) is a useful tool for determining the identity of molecules based on their interaction with electromagnetic fields. If coupled with another method like infrared (IR) vibrational spectroscopy, MS can provide structural information, but in its own right, MS can only provide the mass-to-charge (m/z) ratio of the fragments produced, which may not be enough information to determine the mechanism of the collision-induced dissociation (CID) of the molecule. In this case, theoretical calculations provide a useful companion for MS data and yield clues about the energetics of the dissociation. In this study, negative ion electrospray tandem MS was used to study the CID of the deprotonated dipeptide glycine-serine (Gly-Ser). Though negative ion MS is not as popular a choice as positive ion MS, studies by Bowie et al. show that it yields unique clues about molecular structure which complement positive ion spectroscopy, such as characteristic fragmentations like the loss of formaldehyde from the serine residue.2 The increase in the collision energy in the mass spectrometer alters the flexibility of the dipeptide backbone, enabling isomerizations (reactions not resulting in a fragment loss) and dissociations to take place. The mechanism of the CID of Gly-Ser was studied using two computational methods, B3LYP/6-311+G* and M06-2X/6-311++G**. The main pathway for molecular dissociation was analyzed in 5 conformers in an attempt to verify the initial mechanism proposed by Dr. James Swan after examination of the MS data. The results suggest that the loss of formaldehyde from serine, which Bowie et al. indicates is a characteristic of the presence of serine in a protein residue, is an endothermic reaction that is made possible by the conversion of the translational energy of the ion into internal energy as the ion collides with the inert collision gas. It has also been determined that the M06-2X functional¿s improved description of medium and long-range correlation makes it more effective than the B3LYP functional at finding elusive transition states. M06-2X also more accurately predicts the energy of those transition states than does B3LYP. A second CID mechanism, which passes through intermediates with the same m/z ratio as the main pathway for molecular dissociation, but different structures, including a diketopiperazine intermediate, was also studied. This pathway for molecular dissociation was analyzed with 3 conformers and the M06-2X functional, due to its previously determined effectiveness. The results suggest that the latter pathway, which meets the same intermediate masses as the first mechanism, is lower in overall energy and therefore a more likely pathway of dissociation than the first mechanism.

Bioinformatics tools and databases for the study of human growth hormone

Advances in novel molecular biological diagnostic methods are changing the way of diagnosis and study of metabolic disorders like growth hormone deficiency. Faster sequencing and genotyping methods require strong bioinformatics tools to make sense of the vast amount of data generated by modern laboratories. Advances in genome sequencing and computational power to analyze the whole genome sequences will guide the diagnostics of future. In this chapter, an overview of some basic bioinformatics resources that are needed to study metabolic disorders are reviewed and some examples of bioinformatics analysis of human growth hormone gene, protein and structure are provided.

Reproducible Research: A Bioinformatics Case Study

While scientific research and the methodologies involved have gone through substantial technological evolution the technology involved in the publication of the results of these endeavors has remained relatively stagnant. Publication is largely done in the same manner today as it was fifty years ago. Many journals have adopted electronic formats, however, their orientation and style is little different from a printed document. The documents tend to be static and take little advantage of computational resources that might be available. Recent work, Gentleman and Temple Lang (2004), suggests a methodology and basic infrastructure that can be used to publish documents in a substantially different way. Their approach is suitable for the publication of papers whose message relies on computation. Stated quite simply, Gentleman and Temple Lang propose a paradigm where documents are mixtures of code and text. Such documents may be self-contained or they may be a component of a compendium which provides the infrastructure needed to provide access to data and supporting software. These documents, or compendiums, can be processed in a number of different ways. One transformation will be to replace the code with its output -- thereby providing the familiar, but limited, static document. In this paper we apply these concepts to a seminal paper in bioinformatics, namely The Molecular Classification of Cancer, Golub et al. (1999). The authors of that paper have generously provided data and other information that have allowed us to largely reproduce their results. Rather than reproduce this paper exactly we demonstrate that such a reproduction is possible and instead concentrate on demonstrating the usefulness of the compendium concept itself.

Study of and design procedure for dual circularly polarized waveguide slot arrays

For the past sixty years, waveguide slot radiator arrays have played a critical role in microwave radar and communication systems. They feature a well-characterized antenna element capable of direct integration into a low-loss feed structure with highly developed and inexpensive manufacturing processes. Waveguide slot radiators comprise some of the highest performance—in terms of side-lobe-level, efficiency, etc. — antenna arrays ever constructed. A wealth of information is available in the open literature regarding design procedures for linearly polarized waveguide slots. By contrast, despite their presence in some of the earliest published reports, little has been presented to date on array designs for circularly polarized (CP) waveguide slots. Moreover, that which has been presented features a classic traveling wave, efficiency-reducing beam tilt. This work proposes a unique CP waveguide slot architecture which mitigates these problems and a thorough design procedure employing widely available, modern computational tools. The proposed array topology features simultaneous dual-CP operation with grating-lobe-free, broadside radiation, high aperture efficiency, and good return loss. A traditional X-Slot CP element is employed with the inclusion of a slow wave structure passive phase shifter to ensure broadside radiation without the need for performance-limiting dielectric loading. It is anticipated this technology will be advantageous for upcoming polarimetric radar and Ka-band SatCom systems. The presented design methodology represents a philosophical shift away from traditional waveguide slot radiator design practices. Rather than providing design curves and/or analytical expressions for equivalent circuit models, simple first-order design rules – generated via parametric studies — are presented with the understanding that device optimization and design will be carried out computationally. A unit-cell, S-parameter based approach provides a sufficient reduction of complexity to permit efficient, accurate device design with attention to realistic, application-specific mechanical tolerances. A transparent, start-to-finish example of the design procedure for a linear sub-array at X-Band is presented. Both unit cell and array performance is calculated via finite element method simulations. Results are confirmed via good agreement with finite difference, time domain calculations. Array performance exhibiting grating-lobe-free, broadside-scanned, dual-CP radiation with better than 20 dB return loss and over 75% aperture efficiency is presented.

Estimation of the degree of polarization through computational sensing

The degree of polarization of a refected field from active laser illumination can be used for object identifcation and classifcation. The goal of this study is to investigate methods for estimating the degree of polarization for refected fields with active laser illumination, which involves the measurement and processing of two orthogonal field components (complex amplitudes), two orthogonal intensity components, and the total field intensity. We propose to replace interferometric optical apparatuses with a computational approach for estimating the degree of polarization from two orthogonal intensity data and total intensity data. Cramer-Rao bounds for each of the three sensing modalities with various noise models are computed. Algebraic estimators and maximum-likelihood (ML) estimators are proposed. Active-set algorithm and expectation-maximization (EM) algorithm are used to compute ML estimates. The performances of the estimators are compared with each other and with their corresponding Cramer-Rao bounds. Estimators for four-channel polarimeter (intensity interferometer) sensing have a better performance than orthogonal intensities estimators and total intensity estimators. Processing the four intensities data from polarimeter, however, requires complicated optical devices, alignment, and four CCD detectors. It only requires one or two detectors and a computer to process orthogonal intensities data and total intensity data, and the bounds and estimator performances demonstrate that reasonable estimates may still be obtained from orthogonal intensities or total intensity data. Computational sensing is a promising way to estimate the degree of polarization.

Development of a high performance parallel computing platform and its use in the study of nanostructures : clusters, sheets and tubes .

Small clusters of gallium oxide, technologically important high temperature ceramic, together with interaction of nucleic acid bases with graphene and small-diameter carbon nanotube are focus of first principles calculations in this work. A high performance parallel computing platform is also developed to perform these calculations at Michigan Tech. First principles calculations are based on density functional theory employing either local density or gradient-corrected approximation together with plane wave and gaussian basis sets. The bulk Ga2O3 is known to be a very good candidate for fabricating electronic devices that operate at high temperatures. To explore the properties of Ga2O3 at nonoscale, we have performed a systematic theoretical study on the small polyatomic gallium oxide clusters. The calculated results find that all lowest energy isomers of GamOn clusters are dominated by the Ga-O bonds over the metal-metal or the oxygen-oxygen bonds. Analysis of atomic charges suggest the clusters to be highly ionic similar to the case of bulk Ga2O3. In the study of sequential oxidation of these slusters starting from Ga2O, it is found that the most stable isomers display up to four different backbones of constituent atoms. Furthermore, the predicted configuration of the ground state of Ga2O is recently confirmed by the experimental result of Neumark's group. Guided by the results of calculations the study of gallium oxide clusters, performance related challenge of computational simulations, of producing high performance computers/platforms, has been addressed. Several engineering aspects were thoroughly studied during the design, development and implementation of the high performance parallel computing platform, rama, at Michigan Tech. In an attempt to stay true to the principles of Beowulf revolutioni, the rama cluster was extensively customized to make it easy to understand, and use - for administrators as well as end-users. Following the results of benchmark calculations and to keep up with the complexity of systems under study, rama has been expanded to a total of sixty four processors. Interest in the non-covalent intereaction of DNA with carbon nanotubes has steadily increased during past several years. This hybrid system, at the junction of the biological regime and the nanomaterials world, possesses features which make it very attractive for a wide range of applicatioins. Using the in-house computational power available, we have studied details of the interaction between nucleic acid bases with graphene sheet as well as high-curvature small-diameter carbon nanotube. The calculated trend in the binding energies strongly suggests that the polarizability of the base molecules determines the interaction strength of the nucleic acid bases with graphene. When comparing the results obtained here for physisorption on the small diameter nanotube considered with those from the study on graphene, it is observed that the interaction strength of nucleic acid bases is smaller for the tube. Thus, these results show that the effect of introducing curvature is to reduce the binding energy. The binding energies for the two extreme cases of negligible curvature (i.e. flat graphene sheet) and of very high curvature (i.e. small diameter nanotube) may be considered as upper and lower bounds. This finding represents an important step towards a better understanding of experimentally observed sequence-dependent interaction of DNA with Carbon nanotubes.