Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 4 uppsatser.

Cells are complex active materials that display fascinating phenomena in response to changes in their physical environments. It is well established that the physical environment dictates cell fate and function; nevertheless, the standard method of culturing and studying cells is on stiff 2- dimensional Petri dishes and glass cover slips. The difference in the magnitude of the stiffness of the substrate in addition to the 2-dimensional character, leads to an incomplete and perhaps misleading picture of the cellular process under scrutiny. As such, an entire field has been dedicated to developing materials that more closely match the characteristics of the natural cellular milieu: biomaterials. Despite significant progress in the field, we are still far from fully recapturing the native environment. Importantly, many of the current strategies for engineering 3-dimensional biomaterials have specific applications yet lack flexibility to be adapted to a wide variety of functions. Our approach is to repurpose existing complex, readily available materials to create a platform for biomaterial production; our biomaterials are derived from plant tissue. Plants have evolved over millions of years to attain structures with intricate geometries for specialized functions. Due to the wide variety of plant structures, one can easily select a plant-based material with analogous features to the tissue of interest. A series of investigations are presented on these novel biomaterials to demonstrate this approach, quantify the mechanical properties, and study the cellular responses. First, we developed a method of processing plant materials to yield decellularized, cellulose-based, biocompatible scaffolds that can be repopulated with mammalian cells. We then created composite materials by casting hydrogels around the cellulose-based scaffolds, which allowed us to incorporate distinct temporal and spatial cues to the local cell populations. Spatial organization of tissues and tissue interfaces remains a primary challenge in biomedical engineering, as tissue interfaces mark complex transitional zones between distinct cell populations. Replicating and repairing this intricate delineation of cell types and mechanical profiles has proven to be a major concern in regenerative medicine. As such, we sought to develop a platform for engineered tissue interfaces, wherein components are combined in a modular fashion into a functional unit. The mechanical cues of the microenvironment affect a plethora of cellular processes, namely cell migration, proliferation, and differentiation. Consequently, the rheological properties of our decellularized, plant-based scaffolds were thoroughly investigated. An in-depth knowledge of the mechanics of the underlying substrate is required to guide future applications and refinements of this technology. The potential applications of these 3-dimensional constructs, as demonstrated through our findings, include designing in vitro models of tissue interactions, new biomaterials for in vivo applications, and studies on fundamental cellular processes. We highlight the significance of our results in a collection of scientific articles, which are presented in the body of this thesis (Chapters 2-5). This work is focused on the use of plant- derived cellulose materials, which forms a subsection of the cellulose biomaterial field. A review article centered on the use of cellulose materials for tissue engineering serves as an introductory chapter.

No description available.

Brain metastases (BM) are the most frequently diagnosed neoplasm to affect the adult central nervous system (CNS), occurring in 20-40% of all cancer patients throughout the course of the disease. The significant advancements to the treatment and control of primary cancers have unfortunately resulted in an increased incidence of BM, however, this complication of cancer progression continues to be met with a dismal outcome and limited therapeutic options. There remains a poor understanding of the several cellular hallmarks of BM, encompassing various molecular, genetic and epigenetic changes that underlay the stages of metastasis, which requires the development of clinically relevant models of metastasis. Our group has previously established the existence of a cancer stem cell/tumor initiating population with patient samples of BM, which established the foundation of this thesis. Thus, I postulate that there exists a subpopulation of cancer stem-like cells, termed brain metastasis initiating cells (BMICs), that is responsible for the initiation of BM and is identifiable by an exclusive subset of genes that regulate self-renewal and metastasis. To support this hypothesis, I established novel experimental models of BM by inoculation of BMICs derived from patient samples of lung-to-brain metastases into intracranial (ICr), intracardiac (ICa), and intrathoracic (IT) routes into NOD/SCID mice. ICr injections validated the presence of a tumor initiating cell (TIC) capacity of BMICs in the secondary environment (brain). From ICa injections I was able to recapitulate macro-metastatic growth, whereas with IT injections I was able to capture the complete metastatic process, from primary lung tumor formation to micro-metastasis growth. Utilizing these models, I determined that the STAT3 pathway and genes SPOCK1 and TWIST2 all contribute to the regulation of BM development, where SPOCK1 may pose as a potential BMIC marker. Further interrogation of the metastatic process utilizing the IT model of BM led to the characterization of “pre-metastasis”, a stage where BMIC cells have crossed the blood-brain barrier and employ mechanisms to invade and seed the neural environment, while simultaneously repressing mechanisms of proliferation and cell growth that would indicate tissue colonization. In summation, I propose a shift in the cancer research paradigm to target the metastatic process itself, to prevent the dissemination of primary tumor cells to the brain. I present models of clinically relevant models of human BM that have proved to be reliable as platforms to interrogate the process of BM, providing insight into the stage of pre-metastasis as a novel therapeutic window into BM prevention and possible extension of patient survival. / Thesis / Doctor of Philosophy (PhD)

Precipitation estimates from the satellite-based Tropical Rainfall Measuring Mission (TRMM) instrumentation play a key role in flood analysis and water resource management across many regions of the world where rain gauge data are sparsely available. Previous studies have produced conflicting results regarding the accuracy of satellite-derived precipitation products, and several authors have called for further examination of their utility, specifically across the Himalaya Mountains region of southern Asia. In this study, daily precipitation estimates generated by TRMM were compared to daily precipitation measurements from a rain gauge network across the country of Nepal. TRMM data were statistically analyzed to quantify their representation of the gauge data during the four precipitation-defined seasons of Nepal. A detailed case study was assembled for the TRMM grid cell characterized by the greatest precipitation gauge density to develop a deeper understanding of local precipitation variability that the coarse resolution TRMM product cannot capture. The results illustrate that TRMM performs relatively well across all seasons, though the performance of TRMM during frozen precipitation events is not clear. In general, TRMM underestimates daily precipitation during the monsoon and pre-monsoon seasons, and overestimates during the winter and post-monsoon season. The case study analysis revealed a threshold for TRMM bias of 10-20mm of daily precipitation, overestimating lighter precipitation events while underestimating heavier precipitation events. Still, TRMM data compare favorably to gauge data, which contributes to the confidence with which they and other satellite-derived data products are used. / Master of Science

No description available.

ITC/USA 2011 Conference Proceedings / The Forty-Seventh Annual International Telemetering Conference and Technical Exhibition / October 24-27, 2011 / Bally's Las Vegas, Las Vegas, Nevada / The measurement result is complete only if it contains the measurand and its units, uncertainty and coverage factor. The uncertainty estimation for the parameters acquired by the FTI is a known process. To execute this task the Institute of Research and Flight Test (IPEV) developed the SALEV© system which is fully compliant with the applicable standards. But the measurement set also includes Derived Parameters. The uncertainty evaluation of these parameters can be solved by cumbersome partial derivates. The search for a simpler solution leads us to a Monte-Carlo based algorithm. The result of using this approach are presented and discussed.

Absolutely pure modules act in ways similar to injective modules. Therefore, through-out this document we investigate many of these properties of absolutely pure modules which are modelled after those similar properties of injective modules. The results we develop can be broken into three categories: localizations, covers and derived functors. We form S1M, an S1R module, for any Rmodule M. We state and prove some known results about localizations. Using these known techniques and properties of localizations, we arrive at conditions on the ring R which make an absolutely pure S1Rmodule into an absolutely pure Rmodule. We then show that under certain conditions, if A is an absolutely pure Rmodule, then S1A will be an absolutely pure S1Rmodule. Also, we dene conditions on the ring R which guarantee that the class of absolutely pure modules will be covering. These include R being left coherent, which we show implies a number of other necessary properties. We also develop derived functors similar to Extn R (whose development uses injective modules). We call these functors Axtn R, prove they are well dened, and develop many of their properties. Then we dene natural maps between Axtn(M;N) and Extn(M;N) and discuss what conditions on M and N guarantee that these maps are isomorphisms.

No description available.

No description available.