Gene Expression Signature in Peripheral Blood Detects Thoracic Aortic Aneurysm

BACKGROUND: Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcome of TAA is preventable by elective surgical repair; however, identifying at-risk individuals is difficult. We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status. Our goal was to identify a distinct gene expression signature in peripheral blood that may identify individuals at risk for TAA. METHODS AND FINDINGS: Whole genome gene expression profiles from 94 peripheral blood samples (collected from 58 individuals with TAA and 36 controls) were analyzed. Significance Analysis of Microarray (SAM) identified potential signature genes characterizing TAA vs. normal, ascending vs. descending TAA, and sporadic vs. familial TAA. Using a training set containing 36 TAA patients and 25 controls, a 41-gene classification model was constructed for detecting TAA status and an overall accuracy of 78+/-6% was achieved. Testing this classifier on an independent validation set containing 22 TAA samples and 11 controls yielded an overall classification accuracy of 78%. These 41 classifier genes were further validated by TaqMan real-time PCR assays. Classification based on the TaqMan data replicated the microarray results and achieved 80% classification accuracy on the testing set. CONCLUSIONS: This study identified informative gene expression signatures in peripheral blood cells that can characterize TAA status and subtypes of TAA. Moreover, a 41-gene classifier based on expression signature can identify TAA patients with high accuracy. The transcriptional programs in peripheral blood leading to the identification of these markers also provide insights into the mechanism of development of aortic aneurysms and highlight potential targets for therapeutic intervention. The classifier genes identified in this study, and validated by TaqMan real-time PCR, define a set of promising potential diagnostic markers, setting the stage for a blood-based gene expression test to facilitate early detection of TAA

Business Taxes in Kansas and Nearby States: Volume 2 -- Results from a Tax Simulation Model

Business taxation continues to be a major concern of legislators, policy makers, and other community leaders. Kansas must offer a sufficiently attractive business climate in order to maintain jobs, income, and a high standard of living in the 1990s. The business climate in a state depends on the productivity of its labor, the proximity of the state to major markets, the strength of its educational system, the quality of life in its communities, and a multitude of factors in addition to taxation. But taxes remain a focus of attention because, unlike quality of life factors, they fall under the direct control of state decision makers. Kansas Inc. has recently funded a two-part study of business taxation and business costs in Kansas and five nearby states: Colorado, Iowa, Missouri, Nebraska, and Oklahoma. The first part of the study, presented in Volume 1 of the Final Report, describes state and local taxation in the region. The report presents a historical overview and then turns to a detailed comparison of specific taxes on income, labor, sales, and property. The study considers the basic tax rate structures of the states and identifies the numerous tax incentives available to new and expanding businesses. The second part of the study, presented in Volume 2 of the Final Report, takes a quantitative approach to interstate tax comparisons. The Institute for Public Policy and Business Research developed a tax and cost simulation model to analyze the impact of business taxes on typical firms in each of several important industries. The estimates of taxes and costs provided by the simulation model provide insights into whether taxes place Kansas at a competitive disadvantage

Business Taxes in Kansas and Nearby States: Executive Summary

Business taxation continues to be a major concern of legislators, policy makers, and other com­munity leaders. Kansas must offer a sufficiently attractive business climate in order to maintain jobs, income, and a high standard of living in the 1990s. The business climate in a state depends on the productivity of its labor, its proximity to major markets, the strength of its educational system, the quality of life in its communities, and a multitude of factors in addition to taxation. But taxes remain a focus of attention because, unlike quality of life factors, they fall under the direct control of state decision makers. Kansas Inc. has recently funded a two-part study of business taxation and business costs in Kansas and five nearby states: Colorado, Iowa, Missouri, Nebraska, and Oklahoma. The first part of the study, presented in Volume 1 of Business Taxes in Kansas and Nearby States, describes state and local taxation in the region. The report presents a historical overview, and then turns to a detailed comparison of specific taxes on income, property, sales, and labor. The study considers the basic tax rate structures of the states and identifies the numerous tax incentives available to new and expanding businesses. The second part of the study, presented in Volume 2 of Business Taxes in Kansas and Nearby States, takes a quantitative approach to interstate tax comparisons. The Institute for Public Policy and Business Research developed a tax and cost simulation model to analyze the impact of business taxes on typical firms in each of several important industries. The estimates of taxes and costs provided by the simulation model provide insights into whether taxes place Kansas at a competitive disadvantage

Business Taxes in Kansas and Nearby States: Volume 1 -- Overview of State and Local Taxation in the Region

Business taxation continues to be a major concern of legislators, policy makers, and other commun­ity leaders. Kansas must offer a sufficiently attractive business climate in order to maintain jobs, income, and a high standard of living in the 1990s. The business climate in a state depends on the productivity of its labor, its proximity to major markets, the strength of its educational system, the quality of life in its communities, and a multitude of factors in addition to taxation. But taxes remain a focus of attention because, unlike quality of life factors, they fall under the direct control of state decision makers. Kansas Inc. has recently funded a two-part study of business taxation and business costs in Kansas and five nearby states: Colorado, Iowa, Missouri, Nebraska, and Oklahoma. The first part of the study, presented in Volume 1 of the Final Report, describes state and local taxation in the region. The report presents a historical overview, and then turns to a detailed comparison of specific taxes on income, prop­erty, sales, and labor. The study considers the basic tax rate structures of the states and identifies the numerous tax incentives available to new and expanding businesses. The second part of the study, presented in Volume 2 of the Final Report, takes a quantitative approach to interstate tax comparisons. The Institute for Public Policy and Business Research developed a tax and cost simulation model to analyze the impact of business taxes on typical firms in each of several important industries. The estimates of taxes and costs provided by the simulation model provide insights into whether taxes place Kansas at a competitive disadvantage

The Impacts of Three Alternative Tax Plans on Selected Firms Results from a Tax Simulation Model for Kansas

This study was commissioned by Kansas Inc. at the request of the State Legislature. The study looks at the impact of a number of proposed tax changes on the Kansas business climate. The specifics of the alternative tax plans considered in the study were outlined by members of a bipartisan committee chaired by Representative Joan Wagnon. The alternate plans were provided to the Institute for Public Policy and Business Research through Kansas IncKansas Inc

Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model.

The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs) can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce.To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model.GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro.Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties.Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue remodeling