Molecular fragment and substituent effect studies of styrene derivatives by electron density shape analysis

The research work leading to the content of this thesis and to the related publications represents a novel way to analyze and characterize some aspects of the most fundamental interactions within molecules, namely through-space and through-bond interactions, which are also relevant to substituent effects. The approach and the results give quantum chemical justification for some components of the associated fundamental phenomena which are often difficult or even impossible to examine separately by experimental means. The results are obtained using well-established, thoroughly tested and verified methods of electron density shape analysis approaches, based on input electron densities obtained by various established quantum chemistry computational methods, such as Hartree-Fock, Density Functional, and Møller-Plesset methodologies. The shape analysis methods, applicable to both complete molecules and locally to molecular fragments such as functional groups, are based on two fundamental theorems of quantum chemistry: the Hohenberg-Kohn theorem and the Holographic Electron Density theorem. The first of these theorems establishes that the molecular electron density must contain all molecular properties, whereas the second of these theorems gives justification that even small molecular fragments, such as a vinyl group in our studies, can be used as a “fingerprint”, fully representing all the unique intramolecular interactions within each molecule. As a consequence of these theorems, the electron density shape analysis methods, when applied to the complete electron density cloud of a target molecule, or locally to that of a molecular fragment, yield shape information which can, in principle, give highly detailed theoretical information about all molecular properties, hence, providing a suitable basis for establishing correlations with experimentally available data about various measured chemical properties. In earlier studies, such shape analysis approaches have been used in various applied fields of chemistry, such as pharmacology and toxicology. The present study describes the use of a series of small molecules, specifically, substituted styrenes for the analysis and shape correlations involving through-bond and through-space correlations. As a consequence of their specific structural features, the chosen molecules appear as ideal candidates to study both effects separately. In spite of their specificity, the results provide some general conclusions which are likely to contribute to a better understanding of far more complex phenomena, such as some of the components contributing to the complex folding pattern of globular proteins and more general interaction problems in the emerging field of molecular design. Even in these latter fields, these two types of interactions, through-space and through-bond, play significant roles as well. The presence of aromatic rings in these styrene derivatives is very useful as through-bond transmitting media whilst the distance between the studied molecular fragments obtained after removing the ring is also nearly optimal to be used in through-space interaction studies. The structural specificities of the model molecules have played an important role in all three publications constituting the main chapters of this thesis. Therefore, there is a strong emphasis on the effect transmitting capabilities of the aromatic ring in all 3 of these papers

Developments and Applications of Synchrotron Radiation Computed Laminography with Micrometer and Nanometer resolution

The aim of this thesis is to enable and to improve computed laminography using synchrotron radiation. This has consisted of optimizing imaging setups, techniques and data treatment methods. Extending the techniques towards better resolution and new contrast modes has been the main driving factor. We have exploited a wide variety of imaging applications, ranging from biology and medical studies to in situ and ex situ studies of materials and microelectronic devices

Aerospace Medicine and Biology: A continuing bibliography (supplement 160)

This bibliography lists 166 reports, articles, and other documents introduced into the NASA scientific and technical information system in October 1976

Digital Holography Microscopy at Lab-on-a-Chip scale: novel algorithms and recording strategies

Il lavoro presentato è mirato allo sviluppo di nuove tecniche di microscopia olografica digitale (Digital Holography Microscopy, DHM), e di opportuni algoritmi numerici per lo studio di biomateriali in ambiente microfluidico. Nello specifico vengono affrontate due problematiche di imaging particolarmente rilevanti nello studio di sistemi Lab-on-a-Chip (LoC). Dapprima è stato studiato il problema della microscopia quantitativa di oggetti biologici osservati attraverso mezzi complessi, come soluzioni torbide e substrati diffondenti, dove la formazione dell’immagine è ostacolata da processi di scattering. Lo studio condotto è stato mirato all’analisi di processi di diffusione da layer statico e da mezzo liquido di tipo colloidale, in regime quasi-statico e dinamico. Sono stati sviluppati a tale scopo dei metodi di registrazione e nuovi algoritmi di ricostruzione dell’immagine olografica (Multi-Look Digital Holography, MLDH) che consentono di fornire un imaging quantitativo dei campioni in esame. Di particolare interesse è il caso di volumi di liquido costituiti da globuli rossi: nel lavoro presentato viene dimostrata la possibilità di studiare, mediante MLDH, processi di adesione cellulare di materiale biologico situato in presenza di flussi di globuli rossi ad alta concentrazione. La possibilità di visualizzare e analizzare quantitativamente materiale biologico all’interno di un capillare o una vena, compensando l’effetto di diffusione del sangue, potrebbe in futuro consentire di studiare la formazione all’interno del vaso di coaguli e placche di colesterolo, sintomatici dell’insorgere di malattie cardiache. La stessa tecnica è in grado di recuperare l’informazione distorta a causa della presenza all’interno del canale di ostacoli statici o quasi-statici (dovuti alla formazione di bio-film o sospensioni batteriche, o causata da processi di fabbricazione del canale microfluidico), aumentando così notevolmente la varietà dei processi biologici analizzabili su piattaforme LoC. Nel lavoro viene anche dimostrato come la presenza di un mezzo torbido possa essere sfruttata vantaggiosamente al fine di migliorare la qualità dell’immagine in sistemi di imaging basati su luce coerente. Parallelamente è stata messa a punto una tecnica interferometrica che, sfruttando il movimento dei campioni nei canali microfluidici, consente di sostituire un sensore convenzionale 2D con un sensore lineare, più compatto e integrabile a bordo del chip, e capace di fornire prestazioni superiori in termini di velocità di acquisizione. Il lavoro presentato descrive il processo di sintesi di un nuovo tipo di ologramma (Space-Time Digital Hologram, STDH), che consente di ottenere un Field-of-View (FoV) illimitato nella direzione del flusso e, quindi, di superare il trade-off esistente tra fattore di ingrandimento e FoV, comune ad ogni tecnica di microscopia convenzionale. Viene inoltre dimostrato che un STDH mantiene le caratteristiche e i vantaggi di un ologramma digitale standard, quali la focalizzazione numerica flessibile, che permette di analizzare contemporaneamente tutti gli oggetti presenti in un volume di liquido, e la possibilità di estrarre la segnatura di fase degli stessi

Microfabricated Devices for Adherent Stem Cell Culture

This thesis details the development of a system of microfabricated devices for the adherent culture of stem cells. The multipotency and self renewal of stem cells make them a potentially abundant source of valuable human cells, for both drug screening and regenerative medicine. However, processing stem cells is challenging due to the complexity of whole cell products, the number of process parameters, and the typical use of adherent culture. It is hypothesised that a microfabricated adherent culture system could facilitate process development with minimal use of resources. Furthermore, microfluidic systems offer advantages in spatial and temporal control over the microenvironment that would benefit process development. An existing prototype culture system is critically evaluated by: assessing the design, modelling fluid flow and dissolved oxygen, and successfully co-culturing human embryonic stem cells, on inactivated mouse embryonic fibroblasts, under perfused conditions. The utilisation of reversible seals facilitates the use of standard tissue-culture polystyrene culture surfaces and manual seeding techniques. The evaluation of the prototype system is used to inform improvements to the design, making it easier to use, increasing the robustness, allowing monitoring of whole culture chambers by microscopy, and improving control over mean pericellular dissolved oxygen. Modelling shows the improved culture system also achieves more uniform distribution of both pericellular dissolved oxygen and fluid velocity. The improved culture system shows similar mouse embryonic stem cell seeding behaviour to tissue culture flasks, but, with medium perfused at 300 μl.h 1, mouse embryonic stem cells reach full confluency in less than 48 h, compared with 72 hours for cells maintained statically in flasks. There is also inconclusive data suggesting that the growth rate is limited by pericellular dissolved oxygen and is, therefore, increased and made more uniform by the inclusion of a gas permeable lid system. The reliability, ease of use, comparability with traditional culture systems, and control over process parameters of the improved system should make it a useful tool for stem cell process development

Aerospace medicine and biology: A cumulative index to the continuing bibliography of the 1973 issues

A cumulative index to the abstracts contained in Supplements 112 through 123 of Aerospace Medicine and Biology A Continuing Bibliography is presented. It includes three indexes: subject, personal author, and corporate source

Reports to the President

A compilation of annual reports for the 1989-1990 academic year, including a report from the President of the Massachusetts Institute of Technology, as well as reports from the academic and administrative units of the Institute. The reports outline the year's goals, accomplishments, honors and awards, and future plans

Aerospace Medicine and Biology: Cumulative index, 1979

This publication is a cumulative index to the abstracts contained in the Supplements 190 through 201 of 'Aerospace Medicine and Biology: A Continuing Bibliography.' It includes three indexes-subject, personal author, and corporate source

2016 Oklahoma Research Day Full Program

This document contains all abstracts from the 2016 Oklahoma Research Day held at Northeastern State University