Electronic Construction Collaboration System – Final Phase, SPR RB02-008, 2014

This phase of the research project involved two major efforts: (1) Complete the implementation of AEC-Sync (formerly known as Attolist) on the Iowa Falls Arch Bridge project and (2) develop a web-based project management system (WPMS) for projects under $10 million. For the first major effort, AEC-Sync was provided for the Iowa Department of Transportation (DOT) in a software as a service agreement, allowing the Iowa DOT to rapidly implement the solution with modest effort. During the 2010 fiscal year, the research team was able to help with the implementation process for the solution. The research team also collected feedback from the Broadway Viaduct project team members before the start of the project and implementation of the solution. For the 2011 fiscal year, the research team collected the post-project surveys from the Broadway Viaduct project members and compared them to the pre-project survey results. The result of the AEC-Sync implementation in the Broadway Viaduct project was a positive one. The project members were satisfied with the performance of AEC-Sync and how it facilitated document management and transparency. In addition, the research team distributed, collected, and analyzed the pre-project surveys for the Iowa Falls Arch Bridge project. During the 2012 fiscal year, the research team analyzed the post-project surveys for the Iowa Falls Arch Bridge project AEC-Sync implementation and found a positive outcome when compared to the pre-project surveys. The second major effort for this project involved the identification and implementation of a WPMS solution for smaller bridge and highway projects. During the 2011 fiscal year, Microsoft SharePoint was selected to be implemented on these smaller highway projects. In this year, workflows for the shop/working drawings for the smaller highway projects specified in Section 1105 of the Iowa DOT Specifications were developed. These workflows will serve as the guide for the development of the SharePoint pages. In order to implement the Microsoft SharePoint pages, the effort of an integrated team proved to be vital because it brought together the expertise required from researchers, programmers, and webpage developers to develop the SharePoint pages.

Electronic Construction Collaboration System—Phase II, SPR RB02-008, 2010

During the first year of research, work was completed to identify Iowa DOT needs for web-based project management system (WPMS) and evaluate how commercially available solutions could meet these needs. Researchers also worked to pilot test custom developed WPMS solutions on Iowa DOT bridge projects. At the end of the first year of research, a Request for Proposals (RFP) was developed and issued by the Iowa DOT for the selection of a commercial WPMS to pilot test on multiple bridge projects. During the second year of research, the responses to the RFP issued during the first year of research were evaluated and a solution was selected. The selected solution, Attolist, was customized, tested, and implemented during the fall of 2009. Beginning in the winter of 2010, the solution was implemented on Iowa DOT projects. Researchers worked to assist in the training, implementation, and performance evaluation of the solution. Work will continue beyond the second year of research to implement Attolist on an additional pilot project. During this time, work will be completed to evaluate the impact of WPMS on Iowa DOT bridge projects.

New reference tables and user-friendly Internet application for predicted heart weights.

BACKGROUND: Knowledge of normal heart weight ranges is important information for pathologists. Comparing the measured heart weight to reference values is one of the key elements used to determine if the heart is pathological, as heart weight increases in many cardiac pathologies. The current reference tables are old and in need of an update. AIMS: The purposes of this study are to establish new reference tables for normal heart weights in the local population and to determine the best predictive factor for normal heart weight. We also aim to provide technical support to calculate the predictive normal heart weight. METHODS: The reference values are based on retrospective analysis of adult Caucasian autopsy cases without any obvious pathology that were collected at the University Centre of Legal Medicine in Lausanne from 2007 to 2011. We selected 288 cases. The mean age was 39.2 years. There were 118 men and 170 women. Regression analyses were performed to assess the relationship of heart weight to body weight, body height, body mass index (BMI) and body surface area (BSA). RESULTS: The heart weight increased along with an increase in all the parameters studied. The mean heart weight was greater in men than in women at a similar body weight. BSA was determined to be the best predictor for normal heart weight. New reference tables for predicted heart weights are presented as a web application that enable the comparison of heart weights observed at autopsy with the reference values. CONCLUSIONS: The reference tables for heart weight and other organs should be systematically updated and adapted for the local population. Web access and smartphone applications for the predicted heart weight represent important investigational tools.

Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator of immune responses and therefore an important therapeutic target for the treatment of diseases that involve pathological immune escape, such as cancer. Here, we describe a robust and sensitive high-throughput screen (HTS) for IDO1 inhibitors using the Prestwick Chemical Library of 1200 FDA-approved drugs and the Maybridge HitFinder Collection of 14,000 small molecules. Of the 60 hits selected for follow-up studies, 14 displayed IC50 values below 20 μM under the secondary assay conditions, and 4 showed an activity in cellular tests. In view of the high attrition rate we used both experimental and computational techniques to identify and to characterize compounds inhibiting IDO1 through unspecific inhibition mechanisms such as chemical reactivity, redox cycling, or aggregation. One specific IDO1 inhibitor scaffold, the imidazole antifungal agents, was chosen for rational structure-based lead optimization, which led to more soluble and smaller compounds with micromolar activity.

Reduction of choroidal neovascularization in mice by adeno-associated virus-delivered anti-vascular endothelial growth factor short hairpin RNA.

BACKGROUND: Strategies leading to the long-term suppression of inappropriate ocular angiogenesis are required to avoid the need for repetitive monthly injections for treatment of diseases of the eye, such as age-related macular degeneration (AMD). The present study aimed to develop a strategy for the sustained repression of vascular endothelial growth factor (VEGF), which is identified as the key player in exudative AMD. METHODS: We have employed short hairpin (sh)RNAs combined with adeno-associated virus (AAV) delivery to obtain the targeted expression of potent gene-regulatory molecules. Anti-VEGF shRNAs were analyzed in human retinal pigment epithelial (RPE) cells using Renilla luciferase screening. For in vivo delivery of the most potent shRNA, self-complementary AAV vectors were packaged in serotype 8 capsids (scAAV2/8-hU6-sh9). In vivo efficacy was evaluated either by injection of scAAV2/8-hU6-sh9 into murine hind limb muscles or in a laser-induced murine model of choroidal neovascularization (CNV) following scAAV2/8-hU6-sh9 subretinal delivery. RESULTS: Plasmids encoding anti-VEGF shRNAs showed efficient knockdown of human VEGF in RPEs. Intramuscular administration led to localized expression and 91% knockdown of endogenous murine (m)VEGF. Subsequently, the ability of AAV2/8-encoded shRNAs to impair vessel formation was evaluated in the murine model of CNV. In this model, the sizes of the CNV were significantly reduced (up to 48%) following scAAV2/8-hU6-sh9 subretinal delivery. CONCLUSIONS: Using anti-VEGF vectors, we have demonstrated efficient silencing of endogenous mVEGF and showed that subretinal administration of scAAV2/8-hU6-sh9 has the ability to impair vessel formation in an AMD animal model. Thus, AAV-encoded shRNA can be used for the inhibition of neovascularization, leading to the development of sustained anti-VEGF therapy. Copyright © 2012 John Wiley & Sons, Ltd.

Issue review : electronic document management system or EDMS.

This issue review provides an overview of the electronic documents management system, or EDMS project.

Issue review : electronic document management system, or EDMS.

This issue review provides an overview of the electronic document management system, or EDMS, project, withing the judicial branch and courts.

Phylogenetics of Olea (Oleaceae) based on plastid and nuclear ribosomal DNA sequences: tertiary climatic shifts and lineage differentiation times.

BACKGROUND AND AIMS: The genus Olea (Oleaceae) includes approx. 40 taxa of evergreen shrubs and trees classified in three subgenera, Olea, Paniculatae and Tetrapilus, the first of which has two sections (Olea and Ligustroides). Olive trees (the O. europaea complex) have been the subject of intensive research, whereas little is known about the phylogenetic relationships among the other species. To clarify the biogeographical history of this group, a molecular analysis of Olea and related genera of Oleaceae is thus necessary. METHODS: A phylogeny was built of Olea and related genera based on sequences of the nuclear ribosomal internal transcribed spacer-1 and four plastid regions. Lineage divergence and the evolution of abaxial peltate scales, the latter character linked to drought adaptation, were dated using a Bayesian method. KEY RESULTS: Olea is polyphyletic, with O. ambrensis and subgenus Tetrapilus not sharing a most recent common ancestor with the main Olea clade. Partial incongruence between nuclear and plastid phylogenetic reconstructions suggests a reticulation process in the evolution of subgenus Olea. Estimates of divergence times for major groups of Olea during the Tertiary were obtained. CONCLUSIONS: This study indicates the necessity of revising current taxonomic boundaries in Olea. The results also suggest that main lines of evolution were promoted by major Tertiary climatic shifts: (1) the split between subgenera Olea and Paniculatae appears to have taken place at the Miocene-Oligocene boundary; (2) the separation of sections Ligustroides and Olea may have occurred during the Early Miocene following the Mi-1 glaciation; and (3) the diversification within these sections (and the origin of dense abaxial indumentum in section Olea) was concomitant with the aridification of Africa in the Late Miocene.

A plan for an electronic library and information services program for Iowa : presented to the Honorable Terry E. Branstad and members of the Iowa General Assembly, 1995

This document summarizes the conclusions and recommendations of the Library Services Advisory Council who were appointed by Governor Terry E. Branstad to develop a coordinated, cost-effective and comprehensive plan for the implementation of an electronic statewide library and information services program.

Cardiac repair with allogeneic mesenchymal stem cells after myocardial infarction.

Over the past decade, use of autologous bone marrow-derived mononuclear cells (BMCs) has proven to be safe in phase-I/II studies in patients with myocardial infarction (MI). Taken as a whole, results support a modest yet significant improvement in cardiac function in cell-treated patients. Skeletal myoblasts, adipose-derived stem cells, and bone marrow-derived mesenchymal stem cells (MSCs) have also been tested in clinical studies. MSCs expand rapidly in vitro and have a potential for multilineage differentiation. However, their regenerative capacity decreases with aging, limiting efficacy in old patients. Allogeneic MSCs offer several advantages over autologous BMCs; however, immune rejection of allogeneic cells remains a key issue. As human MSCs do not express the human leukocyte antigen (HLA) class II under normal conditions, and because they modulate T-cell-mediated responses, it has been proposed that allogeneic MSCs may escape immunosurveillance. However, recent data suggest that allogeneic MSCs may switch immune states in vivo to express HLA class II, present alloantigen and induce immune rejection. Allogeneic MSCs, unlike syngeneic ones, were eliminated from rat hearts by 5 weeks, with a loss of functional benefit. Allogeneic MSCs have also been tested in initial clinical studies in cardiology patients. Intravenous allogeneic MSC infusion has proven to be safe in a phase-I trial in patients with acute MI. Endoventricular allogeneic MSC injection has been associated with reduced adverse cardiac events in a phase-II trial in patients with chronic heart failure. The long-term safety and efficacy of allogeneic MSCs for cardiac repair remain to be established. Ongoing phase-II trials are addressing these issues.

Endogenous angiotensin II induces atherosclerotic plaque vulnerability and elicits a Th1 response in ApoE-/- mice.

Rupture of vulnerable plaques is the main cause of acute cardiovascular events. However, mechanisms responsible for transforming a stable into a vulnerable plaque remain elusive. Angiotensin II, a key regulator of blood pressure homeostasis, has a potential role in atherosclerosis. To study the contribution of angiotensin II in plaque vulnerability, we generated hypertensive hypercholesterolemic ApoE-/- mice with either normal or endogenously increased angiotensin II production (renovascular hypertension models). Hypertensive high angiotensin II ApoE-/- mice developed unstable plaques, whereas in hypertensive normal angiotensin II ApoE-/- mice plaques showed a stable phenotype. Vulnerable plaques from high angiotensin II ApoE-/- mice had thinner fibrous cap (P<0.01), larger lipid core (P<0.01), and increased macrophage content (P<0.01) than even more hypertensive but normal angiotensin II ApoE-/- mice. Moreover, in mice with high angiotensin II, a skewed T helper type 1-like phenotype was observed. Splenocytes from high angiotensin II ApoE-/- mice produced significantly higher amounts of interferon (IFN)-gamma than those from ApoE-/- mice with normal angiotensin II; secretion of IL4 and IL10 was not different. In addition, we provide evidence for a direct stimulating effect of angiotensin II on lymphocyte IFN-gamma production. These findings suggest a new mechanism in plaque vulnerability demonstrating that angiotensin II, within the context of hypertension and hypercholesterolemia, independently from its hemodynamic effect behaves as a local modulator promoting the induction of vulnerable plaques probably via a T helper switch.

IL-12-mediated STAT4 signaling and TCR signal strength cooperate in the induction of CD40L in human and mouse CD8(+) T cells.

CD40L is one of the key molecules bridging the activation of specific T cells and the maturation of professional and nonprofessional antigen-presenting cells including B cells. CD4(+) T cells have been regarded as the major T-cell subset that expresses CD40L upon cognate activation; however, we demonstrate here that a putative CD8(+) helper T-cell subset expressing CD40L is induced in human and murine CD8(+) T cells in vitro and in mice immunized with antigen-pulsed dendritic cells. IL-12 and STAT4-mediated signaling was the major instructive cytokine signal boosting the ability of CD8(+) T cells to express CD40L both in vitro and in vivo. Additionally, TCR signaling strength modulated CD40L expression in CD8(+) T cells after primary differentiation in vitro as well as in vivo. The induction of CD40L in CD8(+) T cells regulated by IL-12 and TCR signaling may enable CD8(+) T cells to respond autonomously of CD4(+) T cells. Thus, we propose that under proinflammatory conditions, a self-sustaining positive feedback loop could facilitate the efficient priming of T cells stimulated by high affinity peptide displaying APCs.

MR connectomics: a conceptual framework for studying the developing brain.

THE COMBINATION OF ADVANCED NEUROIMAGING TECHNIQUES AND MAJOR DEVELOPMENTS IN COMPLEX NETWORK SCIENCE, HAVE GIVEN BIRTH TO A NEW FRAMEWORK FOR STUDYING THE BRAIN: "connectomics." This framework provides the ability to describe and study the brain as a dynamic network and to explore how the coordination and integration of information processing may occur. In recent years this framework has been used to investigate the developing brain and has shed light on many dynamic changes occurring from infancy through adulthood. The aim of this article is to review this work and to discuss what we have learned from it. We will also use this body of work to highlight key technical aspects that are necessary in general for successful connectome analysis using today's advanced neuroimaging techniques. We look to identify current limitations of such approaches, what can be improved, and how these points generalize to other topics in connectome research.

Needs, expectations, and concerns of medical students regarding end-of-life issues before the introduction of a mandatory undergraduate palliative care curriculum.

BACKGROUND: In the past, implementation of effective palliative care curricula has emerged as a priority in medical education. In order to gain insight into medical students' needs and expectations, we conducted a survey before mandatory palliative care education was introduced in our faculty. METHODS: Seven hundred nine students answered a questionnaire mainly consisting of numeric rating scales (0-10). RESULTS: Participants attributed a high importance to palliative care for their future professional life (mean, 7.51 ± 2.2). For most students, symptom control was crucial (7.72 ± 2.2). However, even higher importance was assigned to ethical and legal issues (8.16 ± 1.9). "Self-reflection regarding their own role as a physician caring for the terminally ill along with psychological support" was also regarded as highly important (7.25 ± 2.4). Most students were moderately concerned at the prospect of being confronted with suffering and death (5.13 ± 2.4). This emotional distress was rated significantly higher by female students (5.4 ± 2.4 versus 4.6 ± 2.4; p < 0.001). Seventeen percent of all students rated their distress as being 7 of 10 or higher, which indicates a considerable psychological strain in terms of dealing with end-of-life issues in the future. Professional or personal experience with terminally ill persons lowered these anxieties significantly (4.99 ± 2.34 versus 5.47 ± 2.5, p < 0.05). CONCLUSIONS: Medical students stated a remarkably high interest in learning palliative care competencies. Responding to their specific concerns and needs-especially with regard to the acquisition of emotional coping skills-may be key for the development of successful palliative care curricula.