Simple Objective Detection of Human Lyme Disease Infection Using Immuno-PCR and a Single Recombinant Hybrid Antigen

A serology-based tiered approach has, to date, provided the most effective means of laboratory confirmation of clinically suspected cases of Lyme disease, but it lacks sensitivity in the early stages of disease and is often dependent on subjectively scored immunoblots. We recently demonstrated the use of immuno-PCR (iPCR) for detecting Borrelia burgdorferi antibodies in patient serum samples that were positive for Lyme disease. To better understand the performance of the Lyme disease iPCR assay, the repeatability and variability of the background of the assay across samples from a healthy population (n = 36) were analyzed. Both of these parameters were found to have coefficients of variation of \u3c 3%. Using eight antigen-specific iPCR assays and positive call thresholds established for each assay, iPCR IgM and/or IgG diagnosis from Lyme disease patient serum samples (n = 12) demonstrated a strong correlation with that of 2-tier testing. Furthermore, a simplified iPCR approach using a single hybrid antigen and detecting only IgG antibodies confirmed the 2-tier diagnosis in the Lyme disease patient serum samples (n = 12). Validation of the hybrid antigen IgG iPCR assay using a blinded panel of Lyme disease and non-Lyme disease patient serum samples (n = 92) resulted in a sensitivity of 69% (95% confidence interval [CI], 50% to 84%), compared to that of the 2-tier analysis at 59% (95% CI, 41% to 76%), and a specificity of 98% (95% CI, 91% to 100%) compared to that of the 2-tier analysis at 97% (95% CI, 88% to 100%). A single-tier hybrid antigen iPCR assay has the potential to be an improved method for detecting host-generated antibodies against B. burgdorferi

Mechanical design of rotors for permanent magnet high speed electric motors for turbocharger applications

Realization of electrically boosted turbochargers requires electric motors capable of operating at very high speeds. These motors often use a permanent magnet rotor with the magnets retained within an interference fit external sleeve. Whilst it is possible to model such systems numerically, these models are an inefficient tool for design optimization. Current analytical models of rotors typically consider the stresses induced by the shrink fit of the sleeve separately from the stresses generated by centripetal forces due to rotation. However, such an approach ignores the frictional interaction between the components in the axial direction. This paper presents an analytical model that simultaneously accounts for interaction between the magnet and outer sleeve in both the radial and axial directions at designed interference and with the assembly subjected to centripetal and thermal loads. Numerical models presented show that with only moderate coefficients of friction and rotor lengths; axial load transfer between magnet and sleeve takes place over a short distance at the ends of the assembly. The paper then demonstrates how the analytical model aids definition of a feasible set of rotor designs and selection of an optimum design

Understanding human vulnerability to climate change: A global perspective on index validation for adaptation planning

Climate change is a severe global threat. Research on climate change and vulnerability to natural hazards has made significant progress over the last decades. Most of the research has been devoted to improving the quality of climate information and hazard data, including exposure to specific phenomena, such as flooding or sea-level rise. Less attention has been given to the assessment of vulnerability and embedded social, economic and historical conditions that foster vulnerability of societies. A number of global vulnerability assessments based on indicators have been developed over the past years. Yet an essential question remains how to validate those assessments at the global scale. This paper examines different options to validate global vulnerability assessments in terms of their internal and external validity, focusing on two global vulnerability indicator systems used in the WorldRiskIndex and the INFORM index. The paper reviews these global index systems as best practices and at the same time presents new analysis and global results that show linkages between the level of vulnerability and disaster outcomes. Both the review and new analysis support each other and help to communicate the validity and the uncertainty of vulnerability assessments. Next to statistical validation methods, we discuss the importance of the appropriate link between indicators, data and the indicandum. We found that mortality per hazard event from floods, drought and storms is 15 times higher for countries ranked as highly vulnerable compared to those classified as low vulnerable. These findings highlight the different starting points of countries in their move towards climate resilient development. Priority should be given not just to those regions that are likely to face more severe climate hazards in the future but also to those confronted with high vulnerability already

On the political feasibility of climate change mitigation pathways: Is it too late to keep warming below 1.5°C?

Keeping global warming below 1.5°C is technically possible but is it politically feasible? Understanding political feasibility requires answering three questions: (a) “Feasibility of what?,” (b) “Feasibility when and where?,” and (c) “Feasibility for whom?.” In relation to the 1.5°C target, these questions translate into (a) identifying specific actions comprising the 1.5°C pathways; (b) assessing the economic and political costs of these actions in different socioeconomic and political contexts; and (c) assessing the economic and institutional capacity of relevant social actors to bear these costs. This view of political feasibility stresses costs and capacities in contrast to the prevailing focus on benefits and motivations which mistakes desirability for feasibility. The evidence on the political feasibility of required climate actions is not systematic, but clearly indicates that the costs of required actions are too high in relation to capacities to bear these costs in relevant contexts. In the future, costs may decline and capacities may increase which would reduce political constraints for at least some solutions. However, this is unlikely to happen in time to avoid a temperature overshoot. Further research should focus on exploring the “dynamic political feasibility space” constrained by costs and capacities in order to find more feasible pathways to climate stabilization. This article is categorized under: The Carbon Economy and Climate Mitigation > Decarbonizing Energy and/or Reducing Demand

A Synthesis of Global Urbanization Projections

This chapter reviews recent literature on global projections of future urbanization, covering the population, economic and physical extent perspectives. We report on several recent findings based on studies and reports on global patterns of urbanization. Specifically, we review new literature that makes projections about the spatial pattern, rate, and magnitude of urbanization change in the next 30–50 years. While projections should be viewed and utilized with caution, the chapter synthesis reports on several major findings that will have significant socioeconomic and environmental impacts including the following: By 2030, world urban population is expected to increase from the current 3.4 billion to almost 5 billion; Urban areas dominate the global economy – urban economies currently generate more than 90 % of global Gross Value Added; From 2000 to 2030, the percent increase in global urban land cover will be over 200 % whereas the global urban population will only grow by a little over 70 %. Our synthesis of recent projections suggest that between 50%–60% of the total urban land in existence in 2030 will be built in the first three decades of the 21st century. Challenges and limitations of urban dynamic projections are discussed, as well as possible innovative applications and potential pathways towards sustainable urban futures

Evaluating Knowledge to Support Climate Action: A Framework for Sustained Assessment. Report of an Independent Advisory Committee on Applied Climate Assessment

As states, cities, tribes, and private interests cope with climate damages and seek to increase preparedness and resilience, they will need to navigate myriad choices and options available to them. Making these choices in ways that identify pathways for climate action that support their development objectives will require constructive public dialogue, community participation, and flexible and ongoing access to science- and experience-based knowledge. In 2016, a Federal Advisory Committee (FAC) was convened to recommend how to conduct a sustained National Climate Assessment (NCA) to increase the relevance and usability of assessments for informing action. The FAC was disbanded in 2017, but members and additional experts reconvened to complete the report that is presented here. A key recommendation is establishing a new nonfederal "climate assessment consortium" to increase the role of state/local/tribal government and civil society in assessments. The expanded process would 1) focus on applied problems faced by practitioners, 2) organize sustained partnerships for collaborative learning across similar projects and case studies to identify effective tested practices, and 3) assess and improve knowledge-based methods for project implementation. Specific recommendations include evaluating climate models and data using user-defined metrics; improving benefit-cost assessment and supporting decision-making under uncertainty; and accelerating application of tools and methods such as citizen science, artificial intelligence, indicators, and geospatial analysis. The recommendations are the result of broad consultation and present an ambitious agenda for federal agencies, state/local/tribal jurisdictions, universities and the research sector, professional associations, nongovernmental and community-based organizations, and private-sector firms.New York State Energy Research and Development Authority [123416]; Columbia University's Earth Institute; American Meteorological Society; Kresge Foundation6 month embargo; published online: 21 May 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The Onconeural Antigen cdr2 Is a Novel APC/C Target that Acts in Mitosis to Regulate C-Myc Target Genes in Mammalian Tumor Cells

Cdr2 is a tumor antigen expressed in a high percentage of breast and ovarian tumors and is the target of a naturally occurring tumor immune response in patients with paraneoplastic cerebellar degeneration, but little is known of its regulation or function in cancer cells. Here we find that cdr2 is cell cycle regulated in tumor cells with protein levels peaking in mitosis. As cells exit mitosis, cdr2 is ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) and rapidly degraded by the proteasome. Previously we showed that cdr2 binds to the oncogene c-myc, and here we extend this observation to show that cdr2 and c-myc interact to synergistically regulate c-myc-dependent transcription during passage through mitosis. Loss of cdr2 leads to functional consequences for dividing cells, as they show aberrant mitotic spindle formation and impaired proliferation. Conversely, cdr2 overexpression is able to drive cell proliferation in tumors. Together, these data indicate that the onconeural antigen cdr2 acts during mitosis in cycling cells, at least in part through interactions with c-myc, to regulate a cascade of actions that may present new targeting opportunities in gynecologic cancer

Notch signaling in glioblastoma: a developmental drug target?

Malignant gliomas are among the most devastating tumors for which conventional therapies have not significantly improved patient outcome. Despite advances in imaging, surgery, chemotherapy and radiotherapy, survival is still less than 2 years from diagnosis and more targeted therapies are urgently needed. Notch signaling is central to the normal and neoplastic development of the central nervous system, playing important roles in proliferation, differentiation, apoptosis and cancer stem cell regulation. Notch is also involved in the regulation response to hypoxia and angiogenesis, which are typical tumor and more specifically glioblastoma multiforme (GBM) features. Targeting Notch signaling is therefore a promising strategy for developing future therapies for the treatment of GBM. In this review we give an overview of the mechanisms of Notch signaling, its networking pathways in gliomas, and discuss its potential for designing novel therapeutic approaches