Molecular Biology of Brain Metastasis

Metastasis to the central nervous system (CNS) remains a major cause of morbidity and mortality in patients with systemic cancer. As the length of survival in patients with systemic cancer improves, thanks to multimodality therapies, focusing on metastases to the CNS becomes of paramount importance. Unique interactions between the brain’s micro-environment, blood-brain barrier, and tumor cells are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. This review will focus on the pathophysiology, epigenetics, and immunobiology of brain metastases in order to understand the metastatic cascade. Cancer cells escape the primary tumor, intravasate into blood vessels, survive the hematogenous dissemination to the CNS, arrest in brain capillaries, extravasate, proliferate, and develop angiogenic abilities to establish metastases. Molecular biology, genetics, and epigenetics are rapidly expanding, enabling us to advance our knowledge of the underlying mechanisms involved. Research approaches using cell lines that preferentially metastasize in vivo to the brain and in vitro tissue-based studies unfold new molecular leads into the disease. It is important to identify and understand the molecular pathways of the metastatic cascade in order to target the investigation and development of more effective therapies and research directions.     

Medullary Thymic Epithelial Cells and Central Tolerance in Autoimmune Hepatitis Development: Novel Perspective from a New Mouse Model

Autoimmune hepatitis (AIH) is an immune-mediated disorder that affects the liver parenchyma. Diagnosis usually occurs at the later stages of the disease, complicating efforts towards understanding the causes of disease development. While animal models are useful for studying the etiology of autoimmune disorders, most of the existing animal models of AIH do not recapitulate the chronic course of the human condition. In addition, approaches to mimic AIH-associated liver inflammation have instead led to liver tolerance, consistent with the high tolerogenic capacity of the liver. Recently, we described a new mouse model that exhibited spontaneous and chronic liver inflammation that recapitulated the known histopathological and immunological parameters of AIH. The approach involved liver-extrinsic genetic engineering that interfered with the induction of T-cell tolerance in the thymus, the very process thought to inhibit AIH induction by liver-specific expression of exogenous antigens. The mutation led to depletion of specialized thymic epithelial cells that present self-antigens and eliminate autoreactive T-cells before they exit the thymus. Based on our findings, which are summarized below, we believe that this mouse model represents a relevant experimental tool towards elucidating the cellular and molecular aspects of AIH development and developing novel therapeutic strategies for treating this disease.     

Investigating the enhancement of three-dimensional diffraction tomography by using multiple illumination planes

The three dimensional (3-D) extension of the two well-known diffraction tomography algorithms, namely, direct Fourier interpolation (DFI) and filtered backpropagation (FBP), are presented and the problem of the data needed for a full 3-D reconstruction is investigated. These algorithms can be used efficiently to solve the inverse scattering problem for weak scatterers in the frequency domain under the first-order Born and Rytov approximations. Previous attempts of 3-D reconstruction with plane-wave illumination have used data obtained with the incident direction restricted at the xy plane. However, we show that this restriction results in the omission of the contribution of certain spatial frequencies near the omegaz axis for the final reconstruction. The effect of this omission is studied by comparing the results of reconstruction with and without data obtained from other incident directions that fill the spatial frequency domain. We conclude that the use of data obtained for incident direction in only the xy plane is sufficient to achieve a satisfactory quality of reconstruction for a class of objects presenting smooth variation along the z axis, while abrupt variations along the z axis cannot be imaged. This result should be taken into account in the process of designing the acquisition geometry of a tomography scanner.     

An empirical analysis of farm vehicle crash injury severities on Iowa's public road system

Farm vehicle crashes are a major safety concern for farmers as well as all other users of the public road system in agricultural states. Using data on farm vehicle crashes that occurred on Iowa's public roads between 2004 and 2006, we estimate a multinomial logit model to identify crash-, farm vehicle-, and driver-specific factors that determine farm vehicle crash injury severity outcomes. Estimation findings indicate that there are crash patterns (rear-end manner of collision; single-vehicle crash; farm vehicle crossed the centerline or median) and conditions (obstructed vision and crash in rural area; dry road, dark lighting, speed limit 55 mph or higher, and harvesting season), as well as farm vehicle and driver-contributing characteristics (old farm vehicle, young farm vehicle driver), where targeted intervention can help reduce the severity of crash outcomes. Determining these contributing factors and their effect is the first step to identifying countermeasures and safety strategies in a bid to improve transportation safety for all users on the public road system in Iowa as well as other agricultural states.     

Arsenic removal from geothermal waters with zero-valent iron--effect of temperature, phosphate and nitrate

Field column studies and laboratory batch experiments were conducted in order to assess the performance of zero-valent iron in removing arsenic from geothermal waters in agricultural regions where phosphates and nitrates were present. A field pilot study demonstrated that iron filings could remove arsenic, phosphate and nitrate from water. In addition, batch studies were performed to evaluate the effect of temperature, phosphate and nitrate on As(III) and As(V) removal rates. All batch experiments were conducted at three temperatures (20, 30 and 40 degrees C). Pseudo-first-order reaction rate constants were calculated for As(III), As(V), phosphate, nitrate and ammonia for all temperatures. As(V) exhibited greater removal rates than As(III). The presence of phosphate and nitrate decreased the rates of arsenic removal. The temperature of the water played a dominant role on the kinetics of arsenic, phosphate and nitrate removal. Nitrate reduction resulted in the formation of nitrite and ammonia. In addition, the activation energy, Eact, and the constant temperature coefficient, theta were determined for each removal process.     

Growth of low temperature silicon nano-structures for electronic and electrical energy generation applications

This paper represents the lowest growth temperature for silicon nano-wires (SiNWs) via a vapour-liquid–solid method, which has ever been reported in the literature. The nano-wires were grown using plasma-enhanced chemical vapour deposition technique at temperatures as low as 150°C using gallium as the catalyst. This study investigates the structure and the size of the grown silicon nano-structure as functions of growth temperature and catalyst layer thickness. Moreover, the choice of the growth temperature determines the thickness of the catalyst layer to be used.The electrical and optical characteristics of the nano-wires were tested by incorporating them in photovoltaic solar cells, two terminal bistable memory devices and Schottky diode. With further optimisation of the growth parameters, SiNWs, grown by our method, have promising future for incorporation into high performance electronic and optical devices.