Crystal structure prediction for multicomponent systems: energy models and structure generation

Crystalline materials have a wide application in the pharmaceutical and agrochemical sectors. The aim of Crystal Structure Prediction (CSP) is to conduct polymorph screening by predicting all possible polymorphs given the chemical diagram of a compound. Various computational programmes have been developed for both academic and industrial use. However, the application to hydrate systems remains challenging. The aim of this thesis is to explore and improve the applicability of CSP for hydrates. In this thesis, I first examined the applicability of a current lattice energy model for hydrates: This model consists of anisotropic distributed multipole moments derived from isolated-molecule quantum mechanical calculations to model the electrostatic interactions, combined with isotropic atom-atom exp-6 Buckingham potential along with empirical pa- rameters to model repulsion and dispersion interactions. It has been shown to be successful in determining the low-energy structures of small organic crystals. By giving 107 exper- imental hydrates extracted from the Cambridge Structural Database as starting points, I found that the energy model is able to reproduce around 95% of the structural geometry with different quantum mechanical levels of theory. The relative stability ordering based on the lattice energy for computed structures was, however, not always satisfactory and varies with the level of theory adopted. The energy model also revealed an underestima- tion of the binding energy for hydrate and hydrogen-bonding systems. The accuracy of our current energy model was insufficient for modelling crystals with complex short-range interactions, especially hydrogen bonds. I postulated that this can be addressed with the inclusion of an explicit induction energy correction in the model. Hence I examined the use of the isolated-molecule assumption and the polarisable con- tinuum model (PCM) corrections within hydrate prediction. The electrostatics derived from ab initio molecular charge densities in the gas phase are replaced by simulations within a field of the surrounding molecules represented by point charges. Distributed multipolar representation of the electron density perturbation was applied in the classi- cal polarisation model for the evaluation of the induction energy. The integration of this process for modelling induction into a current CSP methodology was achieved. The im- plementation was based on the recently developed lattice energy minimisation programme known as Crystal Structure Optimizer – Rigid Molecules (CSO-RM) for rigid-body sys- tems, and its companion Crystal Structure Optimizer – Flexible Molecules (CSO-FM) to account for conformational flexibility. I assessed the energy rankings of experimental matches before and after induction corrections for three small organic hydrate systems, namely 2,6-diamino-4(3H)-pyrimidinone, gallic acid and theophylline, as well as demon- strating the importance of induction in the carbamazepine and diglycine crystals. The contribution to the lattice energy from explicit induction term was generally found to favour hydrogen-bonding systems, and has been found to result in significant improvement among polymorphic/computed forms. Another aspect of this work focused on improving the global search efficiency of the initial structure generation. I modified the current methodology, which suffers the frequent occurrence of molecular overlaps. The modification could increase the initial structure generation speed by to four times while preserving the quality of structures generated.Open Acces

Common Polymorphisms in IFI16 and AIM2 Genes Are Associated With Periodontal Disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/1/jper0663-sup-0009.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/2/jper0663-sup-0008.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/3/jper0663-sup-0010.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/4/jper0663-sup-0005.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/5/jper0663.pd

Systemic Dietary Hesperidin Modulation of Osteoclastogenesis, Bone Homeostasis and Periodontal Disease in Mice

This study aimed to evaluate the effects of hesperidin (HE) on in vitro osteoclastogenesis and dietary supplem entation on mouse periodontal disease and femoral bone phenotype. RAW 264.7 cells were stimulated with RANKL in the presence or absence of HE (1, 100 or 500 µM) for 5 days, and evaluated by TRAP, TUNEL and Western Blot (WB) analyses. In vivo, C57BL/6 mice were given HE via oral gavage (125, 250 and 500 mg/kg) for 4 weeks. A sterile silk ligature was placed between the first and second right maxillary molars for 10 days and microcomputed tomography (μCT), histopathological and immunohistochemical evaluation were performed. Femoral bones subjected or not to dietary HE (500 mg/kg) for 6 and 12 weeks were evaluated using μCT. In vitro, HE 500 µM reduced formation of RANKL-stimulated TRAP-positive(+) multinucleated cells (500 µM) as well as c-Fos and NFATc1 protein expression (p < 0.05), markers of osteoclasts. In vivo, dietary HE 500 mg/kg increased the alveolar bone resorption in ligated teeth (p < 0.05) and resulted in a significant increase in TRAP+ cells (p < 0.05). Gingival inflammatory infiltrate was greater in the HE 500 mg/kg group even in the absence of ligature. In femurs, HE 500 mg/kg protected trabecular and cortical bone mass at 6 weeks of treatment. In conclusion, HE impaired in vitro osteoclastogenesis, but on the contrary, oral administration of a high concentration of dietary HE increased osteoclast numbers and promoted inflammation-induced alveolar bone loss. However, HE at 500 mg/kg can promote a bone-sparing effect on skeletal bone under physiological conditions

Telephone number system and ring back tone

Master's thesis in Computer scienceThe development of Computer Network Technology has brought great changes to the modern society, especially e-commerce relying on network has leap-type development. So, how to use the network to improve users’ experience, enabling users’ operation to become faster, more convenient and intuitive, is now the focus of many enterprises. So that customers can stay at home for business, not only convenient for customers, but also saves the company's human resources. I did this project with Altibox company, trying to establish a telephone number system, making individuals and business users can complete the business on the internet, and also implements a simple ring back tones system, the program is built with struts2, hibernate, oracle-database , tomcat, using HTML, JSP and struts2 tag for page display

Untersuchungen zur heterogen-katalytischen SO_2-Entfernung aus simuliertem Rauchgas

Available from the library of Berlin Technische Univ. (DE) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

A molecular thermodynamic approach to phase partitioning of biomolecues and protein folding

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1992.Includes bibliographical references.by Yizu Zhu.Ph.D

Brownian motion and heat kernel on manifolds

Abstract not currently available

Similar but Not Identical Resuscitation Trajectories of the Soil Microbial Community Based on Either DNA or RNA after Flooding

Both drought and flooding are unfavorable for soil microorganisms, but nevertheless, are highly relevant to the extreme weather events that have been predicted to increase in the future. The switch of soil water status from drought to flooding can happen rapidly and microbial activity might be either stimulated or further inhibited, but we have insufficient understanding of the underlying microbial processes. Here, we tracked the changes in soil bacterial and fungal abundance and their community structures, assaying the total (DNA-based) and potentially active (RNA-based) communities in response to abrupt flooding of dry soil. Also, rates of soil respiration and enzyme activity were measured after flooding. Results showed that the bacterial community was found to be more responsive than the fungal community to flooding. The bacterial community responses were clearly classified into three distinct patterns in which the intermediate pattern displayed highly phylogenetic clustering. A transient flourish of Bacilli which belongs to Firmicutes was detected at 8&ndash;48 h of flooding, suggesting its potential importance in the microbial assemblage and subsequent ecosystem functioning. Finally, the accumulative amount of CO2 released was more closely related than enzyme activity to the change in structure of the bacterial community after flooding. In conclusion, these findings extended our understanding of the underlying soil microbial processes following abrupt water condition changes

Overexpression of Sugarcane <i>ScDIR</i> Genes Enhances Drought Tolerance in <i>Nicotiana benthamiana</i>

Dirigent proteins (DIRs) are known to function in lignin biogenesis and to be involved in stress resistance in plants. However, the sugarcane DIRs have not been functionally characterized. In this study, we investigated the DIR−protein−encoding genes in Saccharum spp. (ScDIR) by screening collections of sugarcane databases, monitoring the responses of these genes to drought stress by real−time quantitative PCR, and identifying their heterologous expression in tobacco. Of the 64 ScDIRs identified, four belonging to the DIR−b/d (ScDIR5 and ScDIR11) and DIR−c (ScDIR7 and ScDIR40) subfamilies showed a significant transcriptional response when subjected to drought stress. ScDIR5, ScDIR7, and ScDIR11 are localized in the cell membrane, whereas ScDIR40 is found in the cell wall. The overexpression of these ScDIR genes in tobacco generally increased the drought tolerance of the transgenic lines, with ScDIR7 conferring the highest degree of drought tolerance. The characterization of the physiological and biochemical indicators (superoxide dismutase, catalase, malondialdehyde, and H2O2) confirmed that the ScDIR−overexpressing lines outperformed the wild type. These results demonstrated that specific ScDIRs in sugarcane respond and contribute to tolerance of drought stress, shedding light on potential means of improving drought tolerance in this crop

The Genomic Sequence of the Oral Pathobiont Strain NI1060 Reveals Unique Strategies for Bacterial Competition and Pathogenicity.

Strain NI1060 is an oral bacterium responsible for periodontitis in a murine ligature-induced disease model. To better understand its pathogenicity, we have determined the complete sequence of its 2,553,982 bp genome. Although closely related to Pasteurella pneumotropica, a pneumonia-associated rodent commensal based on its 16S rRNA, the NI1060 genomic content suggests that they are different species thriving on different energy sources via alternative metabolic pathways. Genomic and phylogenetic analyses showed that strain NI1060 is distinct from the genera currently described in the family Pasteurellaceae, and is likely to represent a novel species. In addition, we found putative virulence genes involved in lipooligosaccharide synthesis, adhesins and bacteriotoxic proteins. These genes are potentially important for host adaption and for the induction of dysbiosis through bacterial competition and pathogenicity. Importantly, strain NI1060 strongly stimulates Nod1, an innate immune receptor, but is defective in two peptidoglycan recycling genes due to a frameshift mutation. The in-depth analysis of its genome thus provides critical insights for the development of NI1060 as a prime model system for infectious disease