Development of Quantitative Tools for the Characterization and Analysis of the Blood Brain Barrier in Normal and MPS IIIB Mice

The Blood Brain Barrier (BBB) functions to control homeostasis within the central nervous system (CNS) via strict control over the passage of molecules into and out of the brain. The goal of this barrier is to protect the CNS from harmful external factors while allowing entry of essential nutrients and removal of metabolic byproducts. This restrictive nature of the BBB is due to the protein network at the borders of adjoining cerebral endothelial cells known as the tight junctions (TJs) and the relationship of other supporting cells and proteins such as astrocytes, pericytes, microglia, and the basement membrane and extracellular matrix proteins associated with the endothelial cells. While beneficial in health, the restrictive nature of the BBB has proved to be a hindrance towards drug administration in many brain diseases, blocking pharmaceutical compounds from diffusing out of the blood vessels and into the brain parenchyma. However, certain diseases such as the metabolic disease Mucopolysaccharidosis IIIB, have been shown to cause breaches in the BBB’s integrity, thus suggesting a possible mechanism to administer treatment around this restriction could be to utilize a specific disease’s own pathology. In order to understand the extent of BBB dysfunction a systematic and quantitative analysis of the BBB’s cellular and protein components and their relationships in each disease of interest during the disease’s progression compared to normal conditions is required. This project used advancing technologies in confocal microscopy and 3D image analysis to develop and utilize methodologies to analyze each of the components of the BBB in wild type mice with the goal to quantify their relationship with the cerebral microvascular endothelial cells. In doing so valuable image processing protocols were developed revealing the inadequacies of traditional 2D methods and has helped begin to shed light on the effects of MPS IIIB on the BBB including disrupted endothelial cells along the tight junctions, increased astrocyte contact area and points of contact with endothelial cells, and no changes in the contact area of desmin positive pericytes with endothelial cells

Multivariate phase space reconstruction by nearest neighbor embedding with different time delays

A recently proposed nearest neighbor based selection of time delays for phase space reconstruction is extended to multivariate time series, with an iterative selection of variables and time delays. A case study of numerically generated solutions of the x- and z coordinates of the Lorenz system, and an application to heart rate and respiration data, are used for illustration.Comment: 4 pages, 3 figure

Inextricably intertwined : identity development in adults with a disabled sibling

This study sought to answer the question What is the long-term impact on the identity formation of adults who grew up with a disabled sibling? The bulk of literature exploring the impact of a sibling\u27s disability on his/her non-disabled sibling focuses primarily on children. With so few studies asking non-disabled adult siblings about their experience, however, the research examining this unique relationship lacks depth and scope. In exploring this relationship through an adult lens, there were two primary hypotheses: 1) non-disabled siblings would report having an experience that was rich with both rewards and challenges, and 2) this relationship would have indelibly shaped their self concept and their identity. The study took a qualitative, exploratory approach. The researcher interviewed twelve participants, two men and ten women between the ages of 21 and 58. Their sibling\u27s disabilities covered a range of diagnoses from autism to Down Syndrome to spina bifida. Seven of the participant\u27s siblings were identified as being significantly to severely disabled and four of the DS were identified as being moderately disabled. There were several findings of the study which were divided into eight major categories. Some of these categories touched on how and when participants obtained knowledge of their sibling\u27s disability and the relevance of this knowledge. It also explored each participant\u27s perception of how their sibling\u27s disability shaped their sense of self, others, and the world. These findings highlighted the formative nature of this relationship and the role of disability therein, on adult siblings\u27 identities

The outer kinetochore protein KNL-1 contains a defined oligomerization domain in nematodes

The kinetochore is a large, macromolecular assembly that is essential for connecting chromosomes to microtubules during mitosis. Despite the recent identification of multiple kinetochore components, the nature and organization of the higher order kinetochore structure remain unknown. The outer kinetochore KNL-1/Mis12 complex/Ndc80 complex (KMN) network plays a key role in generating and sensing microtubule attachments. Here, we demonstrate that Caenorhabditis elegans KNL-1 exists as an oligomer and we identify a specific domain in KNL-1 responsible for this activity. An N-terminal KNL-1 domain from both C. elegans and the related nematode C. remanei oligomerizes into a decameric assembly that appears roughly circular when visualized by electron microscopy. Based on sequence and mutational analysis, we identify a small hydrophobic region as responsible for this oligomerization activity. However, mutants that precisely disrupt KNL-1 oligomerization did not alter KNL-1 localization or result in the loss of embryonic viability based on gene replacements in C. elegans. In C. elegans, KNL-1 oligomerization may coordinate with other kinetochore activities to ensure the proper organization, function, and sensory capabilities of the kinetochore-microtubule attachment.Leukemia & Lymphoma Society of America (Scholar Award)National Institute of General Medical Sciences (U.S.) (Grant GM088313)American Cancer Society (Research Scholar Grant 121776

Measuring Information Transfer

An information theoretic measure is derived that quantifies the statistical coherence between systems evolving in time. The standard time delayed mutual information fails to distinguish information that is actually exchanged from shared information due to common history and input signals. In our new approach, these influences are excluded by appropriate conditioning of transition probabilities. The resulting transfer entropy is able to distinguish driving and responding elements and to detect asymmetry in the coupling of subsystems.Comment: 4 pages, 4 Figures, Revte

Webteaching: sequencing of subject matter in relation to prior knowledge of pupils

Two experiments are discussed in which the sequencing procedure of webteaching is compared with a linear sequence for the presentation of text material.\ud \ud In the first experiment variations in the level of prior knowledge of pupils were studied for their influence on the sequencing mode of text presentation. Prior knowledge greatly reduced the effect of the size of sequencing procedures.\ud \ud In the second experiment pupils with a low level of prior knowledge studied a text, following either a websequence or a linear sequence. Webteaching was superior to linear teaching on a number of dependent variables. It is concluded that webteaching is an effective sequencing procedure in those cases where substantial new learning is required

Isothermal and Cyclic Oxidation of an Air Plasma-Sprayed Thermal Barrier Coating System

Thermogravimetric methods for evaluating bond coat oxidation in plasma-sprayed thermal barrier coating (TBC) systems were assessed by high-temperature testing of TBC systems with air plasma-sprayed (APS) Ni-22Cr-10Al-1Y bond coatings and yttria-stabilized zirconia top coatings. High-mass thermogravimetric analysis (at 1150{sup degrees}C) was used to measure bond coat oxidation kinetics. Furnace cycling was used to evaluate APS TBC durability. This paper describes the experimental methods and relative oxidation kinetics of the various specimen types. Characterization of the APS TBCs and their reaction products is discussed