Actin dynamics in the cell cytoplasm and the role of actin associated proteins

Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 1998.Includes bibliographical references.by James L. McGrath.Ph.D

Measuring actin dynamics in endothelium

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1994.Includes bibliographical references (p. [113]-121).by James L. McGrath.M.S

Moving interpretations : using drama-based arts strategies to deepen learning about The diary of a young girl.

Three drama-based arts strategies enhanced middle grades teachers’ and students’ engagement with Anne Frank’s diary and historical circumstances

TEM tomography of pores with application to computational nanoscale flows in nanoporous silicon nitride (NPN)

Silicon nanomembrane technologies (NPN, pnc-Si, and others) have been used commercially as electron microscopy (EM) substrates, and as filters with nanometer-resolution size cut-offs. Combined with EM, these materials provide a platform for catching or suspending nanoscale-size structures for analysis. Usefully, the nanomembrane itself can be manufactured to achieve a variety of nanopore topographies. The size, shapes, and surfaces of nanopores will influence transport, fouling, sieving, and electrical behavior. Electron tomography (ET) techniques used to recreate nanoscale-sized structures would provide an excellent way to capture this variation. Therefore, we modified a sample holder to accept our standardized 5.4 mm × 5.4 mm silicon nanomembrane chips and imaged NPN nanomembranes (50–100 nm thick, 10–100 nm nanopore diameters) using transmission electron microscopy (TEM). After imaging and ET reconstruction using a series of freely available tools (ImageJ, TomoJ, SEG3D2, Meshlab), we used COMSOL Multiphysics™ to simulate fluid flow inside a reconstructed nanopore. The results show flow profiles with significantly more complexity than a simple cylindrical model would predict, with regions of stagnation inside the nanopores. We expect that such tomographic reconstructions of ultrathin nanopores will be valuable in elucidating the physics that underlie the many applications of silicon nanomembranes

Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects.

BackgroundNeural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population.MethodsReplication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case-control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case-control models and NTD groupings in white, African American and Hispanic cohorts from NYS.ResultsOf the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans.ConclusionsWe report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis

The use of TeleMedicine in the Treatment of Pediatric Obesity: Feasibility and Acceptability

This is the peer reviewed version of the following article: Davis, A. M., James, R. L., Boles, R. E., Goetz, J. R., Belmont, J. and Malone, B. (2011), The use of TeleMedicine in the treatment of paediatric obesity: feasibility and acceptability. Maternal & Child Nutrition, 7: 71–79. doi:10.1111/j.1740-8709.2010.00248.x, which has been published in final form at http://doi.org/10.1111/j.1740-8709.2010.00248.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.OBJECTIVE: To assess the feasibility of conducting empirically supported family based pediatric obesity group treatment via telemedicine. METHODS: Seventeen families were randomly assigned to one of two conditions (physician visit, TeleMedicine). Measures included feasibility, satisfaction, and intervention outcome measures such as BMI percentile, and nutrition and activity behaviors. Measures were completed at baseline, post-treatment, and at one-year follow-up. RESULTS: Analyses indicate that both feasibility and satisfaction data regarding the TeleMedicine intervention were positive. Intervention outcome indicates no change in BMI percentile or nutrition and activity behaviors for either treatment group. CONCLUSIONS: A behavioral family-based weight loss intervention delivered via TeleMedicine was well received by both parents and providers. Due to the small sample size, null findings regarding intervention outcome should be interpreted with caution. Future research should focus on methods to increase the impact of this intervention on key outcome variables

Use of the MicroSiM (µSiM) Barrier Tissue Platform for Modeling the Blood-Brain Barrier.

The microSiM (µSiM) is a membrane-based culture platform for modeling the blood-brain barrier (BBB). Unlike conventional membrane-based platforms, the µSiM provides experimentalists with new capabilities, including live cell imaging, unhindered paracrine signaling between 'blood' and 'brain' chambers, and the ability to directly image immunofluorescence without the need for the extraction/remounting of membranes. Here we demonstrate the basic use of the platform to establish monoculture (endothelial cells) and co-culture (endothelial cells and pericytes) models of the BBB using ultrathin nanoporous silicon-nitride membranes. We demonstrate compatibility with both primary cell cultures and human induced pluripotent stem cell (hiPSC) cultures. We provide methods for qualitative analysis of BBB models via immunofluorescence staining and demonstrate the use of the µSiM for the quantitative assessment of barrier function in a small molecule permeability assay. The methods provided should enable users to establish their barrier models on the platform, advancing the use of tissue chip technology for studying human tissues

A design study for the isolation of the 281-3H retention basin at the Savannah River Site using the viscous liquid barrier technology

This report is a description of the design study for a pilot-scale field demonstration of the Viscous Liquid Barrier (VLB) technology, a new subsurface containment technology for waste isolation using a new generation of barrier liquids. The demonstration site was Retention Basin 281-3H, a shallow catchment basin at the Savannah River Site, which is contaminated mainly by radionuclides ({sup 137}Cs, {sup 90}Sr, and {sup 238}Pu). The goals of the field demonstration were (a) to demonstrate the ability to create a continuous subsurface barrier in order to isolate the contaminants, and (b) to demonstrate the continuity, performance, and integrity of the barrier. The site was characterized, and preliminary hydraulic conductivity data were obtained from core samples. Based on the site characteristics and the functional requirements, a conceptual model was developed, the barrier specifications were defined, and lance injection was selected as the emplacement method. The injection strategy for the subsurface conditions at the site was determined using numerical simulations. An appropriate variant of Colloidal Silica (CS) was selected as the barrier liquid based on its relative insensitivity to interactions with the site soils, and the formulation for optimum site performance was determined. A barrier verification strategy, including hydraulic, pneumatic, tracer, and geophysical methods, was developed. A lance water injection test was conducted in order to obtain representative estimates of the hydraulic conductivity and its distribution for the design of the barrier emplacement. The water injection test demonstrated the lack of permeable zones for CS injection, and a decision not to proceed with the barrier emplacement was reached

Brain endothelial tricellular junctions as novel sites for T cell diapedesis across the blood–brain barrier

The migration of activated T cells across the blood-brain barrier (BBB) is a critical step in central nervous system (CNS) immune surveillance and inflammation. Whereas T cell diapedesis across the intact BBB seems to occur preferentially through the BBB cellular junctions, impaired BBB integrity during neuroinflammation is accompanied by increased transcellular T cell diapedesis. The underlying mechanisms directing T cells to paracellular versus transcellular sites of diapedesis across the BBB remain to be explored. By combining in vitro live-cell imaging of T cell migration across primary mouse brain microvascular endothelial cells (pMBMECs) under physiological flow with serial block-face scanning electron microscopy (SBF-SEM), we have identified BBB tricellular junctions as novel sites for T cell diapedesis across the BBB. Downregulated expression of tricellular junctional proteins or protein-based targeting of their interactions in pMBMEC monolayers correlated with enhanced transcellular T cell diapedesis, and abluminal presence of chemokines increased T cell diapedesis through tricellular junctions. Our observations assign an entirely novel role to BBB tricellular junctions in regulating T cell entry into the CNS. This article has an associated First Person interview with the first author of the paper