The POSSIM Force Field in Biochemical Applications

Computational modeling of chemical systems has provided a fast and cost-effective method of approximating molecular properties and interactions, especially those that cannot be determined experimentally. Here, the POSSIM (POlarizable Simulations with Second order Interaction Model) force field is used in order to demonstrate the efficacy of polarizability. While a fixed-charge force field provided an average error of binding energy of about 8.9 kcal/mol with Molecular Dynamics and 4.2 kcal/mol with one inhibitor with Monte Carlo without fitting, it is anticipated that the POSSIM model will achieve a higher accuracy when implemented, with the hope that parameters can be developed as tools for investigating protein-ligand binding

Selection of polymer binders and fabrication of SiC fiber-reinforced reaction-bonded silicon nitride matrix composites

The topics discussed include the following: effects of solvent and polymer exposures on nitriding kinetics of high purity Si powders and on resulting phase distributions; effects of solvent and polymer exposures on Si Surface Chemistry; effects of solvent and polymeric exposures on nitriding kinetics; and fabrication of flexural test samples

Structural and functional distinctions between auditory centers revealed with MRI in living humans

Thesis (Ph. D.)--Harvard University--MIT Division of Health Sciences and Technology, 2005.Vita.Includes bibliographical references.From brainstem to cortex, sound is processed in centers that are functionally and structurally distinct. In animals, invasive electrophysiology and histology has revealed these distinctions and, consequently, organizational principles behind sound processing. In humans, however, comparable demonstrations are sparse. This thesis presents three MRI studies that provide new information regarding structural and functional distinctions between auditory centers in living humans. The first study compared the effect of a fundamental acoustic variable, sound level, on the population neural activity of auditory brainstem, thalamus and cortex. Brainstem and cortex exhibited contrasting sensitivities to sound level (growth in activation followed by saturation in brainstem vs. plateau then growth in cortex), with thalamus showing intermediate properties. The second study identified functional distinctions between cortical areas by spatially mapping the temporal properties of fMRI responses. Using a continuous noise stimulus, we found sustained responses on Heschl's gyrus flanked medially and laterally by more phasic activity. This pattern suggests that transient activity marking the beginning and end of a sound is most pronounced in non-primary areas of auditory cortex. The region of sustained responses may correspond to primary and primary-like areas. Thus, it may present a physiological marker for these areas in neuroimaging studies, something that has long been needed in the auditory neuroimaging field. The third study examined whether auditory cortical areas can be distinguished - in the living human brain - based on classical features of cortical gray matter previously resolvable only in postmortem tissue.(cont.) By mapping the imaging parameter R1, we identified regions of heavily myelinated gray matter that may correspond to primary auditory cortex. We further found greater gray matter myelination of the left temporal lobe, which may be a substrate for higher fidelity temporal processing on the left, and for left-hemispheric speech and language specializations. Being able to resolve gray matter structure in-vivo opens the way to relating cortical physiology and structure directly in living humans in ways previously possible only in animals.by Irina S. Sigalovsky.Ph.D

Computational Chemistry in the High School Classroom

Computational chemistry programs have proven to be powerful research tools, and our project aimed to bring this technology to the classroom. We developed a teaching module based on the web-based software WebMO to address topics chemistry students typically struggle with. Through implementation of the curriculum at Millbury High School, it was found that the students generally possessed a stronger understanding of the topics addressed after using WebMO and that integration of computational chemistry into the classroom is a worthwhile endeavor

Mapping the human cortical surface by combining quantitative T(1) with retinotopy

We combined quantitative relaxation rate (R1= 1/T1) mapping-to measure local myelination-with fMRI-based retinotopy. Gray-white and pial surfaces were reconstructed and used to sample R1 at different cortical depths. Like myelination, R1 decreased from deeper to superficial layers. R1 decreased passing from V1 and MT, to immediately surrounding areas, then to the angular gyrus. High R1 was correlated across the cortex with convex local curvature so the data was first "de-curved". By overlaying R1 and retinotopic maps, we found that many visual area borders were associated with significant R1 increases including V1, V3A, MT, V6, V6A, V8/VO1, FST, and VIP. Surprisingly, retinotopic MT occupied only the posterior portion of an oval-shaped lateral occipital R1 maximum. R1 maps were reproducible within individuals and comparable between subjects without intensity normalization, enabling multi-center studies of development, aging, and disease progression, and structure/function mapping in other modalities

Histological basis of laminar MRI patterns in high resolution images of fixed human auditory cortex

Functional magnetic resonance imaging (fMRI) studies of the auditory region of the temporal lobe would benefit from the availability of image contrast that allowed direct identification of the primary auditory cortex, as this region cannot be accurately located using gyral landmarks alone. Previous work has suggested that the primary area can be identified in magnetic resonance (MR) images because of its relatively high myelin content. However, MR images are also affected by the iron content of the tissue and in this study we sought to confirm that different MR image contrasts did correlate with the myelin content in the grey matter and were not primarily affected by iron content as is the case in the primary visual and somatosensory areas. By imaging blocks of fixed post-mortem cortex in a 7 Tesla scanner and then sectioning them for histological staining we sought to assess the relative contribution of myelin and iron to the grey matter contrast in the auditory region. Evaluating the image contrast in T2*-weighted images and quantitative R2* maps showed a reasonably high correlation between the myelin density of the grey matter and the intensity of the MR images. The correlation with T1-weighted phase sensitive inversion recovery (PSIR) images was better than with the previous two image types, and there were clearly differentiated borders between adjacent cortical areas in these images. A significant amount of iron was present in the auditory region, but did not seem to contribute to the laminar pattern of the cortical grey matter in MR images. Similar levels of iron were present in the grey and white matter and although iron was present in fibres within the grey matter, these fibres were fairly uniformly distributed across the cortex. Thus we conclude that T1- and T2*-weighted imaging sequences do demonstrate the relatively high myelin levels that are characteristic of the deep layers in primary auditory cortex and allow it and some of the surrounding areas to be reliably distinguished

Quantitative MRI provides markers of intra-, inter-regional, and age-related differences in young adult cortical microstructure

Measuring the structural composition of the cortex is critical to understanding typical development, yet few investigations in humans have charted markers in vivo that are sensitive to tissue microstructural attributes. Here, we used a well-validated quantitative MR protocol to measure four parameters (R1, MT, R2*, PD*) that differ in their sensitivity to facets of the tissue microstructural environment (R1, MT: myelin, macromolecular content; R2*: myelin, paramagnetic ions, i.e., iron; PD*: free water content). Mapping these parameters across cortical regions in a young adult cohort (18–39 years, N = 93) revealed expected patterns of increased macromolecular content as well as reduced tissue water content in primary and primary adjacent cortical regions. Mapping across cortical depth within regions showed decreased expression of myelin and related processes – but increased tissue water content – when progressing from the grey/white to the grey/pial boundary, in all regions. Charting developmental change in cortical microstructure cross-sectionally, we found that parameters with sensitivity to tissue myelin (R1 & MT) showed linear increases with age across frontal and parietal cortex (change 0.5–1.0% per year). Overlap of robust age effects for both parameters emerged in left inferior frontal, right parietal and bilateral pre-central regions. Our findings afford an improved understanding of ontogeny in early adulthood and offer normative quantitative MR data for inter- and intra-cortical composition, which may be used as benchmarks in further studies