Pollution Prevention: Factors Behind Toxic Release Reduction in the U.S. Paper Industry

Drs. Tiefenbacher and Solecki analyze the factors associated with, and influential in, the reduction of toxic releases in the U.S. paper industry

Part Two: From City Parks to Regional Green Infrastructure

Part Two: From City Parks to Regional Green Infrastructure -- The Excellent City Park System: What Makes It Great and How to Get There / Peter Harnik -- The Role of Place Attachment in Sustaining Urban Parks / Robert L. Ryan -- The Role of Place Attachment in Sustaining Urban Parks / Robert L. Ryan -- Promoting Health and Fitness through Urban Design / Anne C. Lusk -- A Metropolitan New York Biosphere Reserve? / William D. Solecki and Cynthia Rosenzweig

Deliverable 9.1 - Report on mixtures and implementation strategy in Europe – Assessment of chemical mixtures under consideration of current and future regulatory requirements and scientific approaches

This report gives an overview on the regulatory processes and requirements for risk assessment of chemical mixtures, identifies gaps in the European legislation and summarises potential approaches for the health risk assessment of chemical mixtures

Cross-species epigenetics identifies a critical role for VAV1 in SHH subgroup medulloblastoma maintenance

The identification of key tumorigenic events in Sonic Hedgehog (SHH) subgroup medulloblastomas (MBSHH) will be essential for the development of individualized therapies and improved outcomes. However, beyond confirmation of characteristic SHH pathway mutations, recent genome-wide sequencing studies have not revealed commonly mutated genes with widespread relevance as potential therapeutic targets. We therefore examined any role for epigenetic DNA methylation events in MBSHH using a cross-species approach to candidate identification, prioritization and validation. MBSHH-associated DNA methylation events were first identified in 216 subgrouped human medulloblastomas (50 MBSHH, 28 Wnt/Wingless, 44 Group 3 and 94 Group 4) and their conservation then assessed in tumors arising from four independent murine models of Shh medulloblastoma, alongside any role in tumorigenesis using functional assessments in mouse and human models. This strategy identified widespread regional CpG hypo-methylation of VAV1, leading to its elevated expression, as a conserved aberrant epigenetic event, which characterizes the majority of MBSHH tumors in both species, and is associated with a poor outcome in MBSHH patients. Moreover, direct modulation of VAV1 in mouse and human models revealed a critical role in tumor maintenance, and its abrogation markedly reduced medulloblastoma growth. Further, Vav1 activity regulated granule neuron precursor germinal zone exit and migration initiation in an ex vivo model of early postnatal cerebellar development. These findings establish VAV1 as a critical epigenetically regulated oncogene with a key role in MBSHH maintenance, and highlight its potential as a validated therapeutic target and prognostic biomarker for the improved therapy of medulloblastoma

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

The role of myosin-II in force generation of DRG filopodia and lamellipodia

Differentiating neurons process the mechanical stimulus by exerting the protrusive forces through lamellipodia and filopodia. We used optical tweezers, video imaging and immunocytochemistry to analyze the role of non-muscle myosin-II on the protrusive force exerted by lamellipodia and filopodia from developing growth cones (GCs) of isolated Dorsal Root Ganglia (DRG) neurons. When the activity of myosin-II was inhibited by 30\ue2 ... 1/4M Blebbistatin protrusion/retraction cycles of lamellipodia slowed down and during retraction lamellipodia could not lift up axially as in control condition. Inhibition of actin polymerization with 25\ue2 ...nM Cytochalasin-D and of microtubule polymerization with 500\ue2 ...nM Nocodazole slowed down the protrusion/retraction cycles, but only Cytochalasin-D decreased lamellipodia axial motion. The force exerted by lamellipodia treated with Blebbistatin decreased by 50%, but, surprisingly, the force exerted by filopodia increased by 20-50%. The concomitant disruption of microtubules caused by Nocodazole abolished the increase of the force exerted by filopodia treated with Blebbistatin. These results suggest that; i-Myosin-II controls the force exerted by lamellipodia and filopodia; ii-contractions of the actomyosin complex formed by filaments of actin and myosin have an active role in ruffle formation; iii-myosin-II is an essential component of the structural stability of GCs architecture

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

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

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

Comparison of the force exerted by hippocampal and DRG growth cones

Mechanical properties such as force generation are fundamental for neuronal motility, development and regeneration. We used optical tweezers to compare the force exerted by growth cones (GCs) of neurons from the Peripheral Nervous System (PNS), such as Dorsal Root Ganglia (DRG) neurons, and from the Central Nervous System (CNS) such as hippocampal neurons. Developing GCs from dissociated DRG and hippocampal neurons were obtained from P1-P2 and P10-P12 rats. Comparing their morphology, we observed that the area of GCs of hippocampal neurons was 8-10 \ub5m(2) and did not vary between P1-P2 and P10-P12 rats, but GCs of DRG neurons were larger and their area increased from P1-P2 to P10-P12 by 2-4 times. The force exerted by DRG filopodia was in the order of 1-2 pN and never exceeded 5 pN, while hippocampal filopodia exerted a larger force, often in the order of 5 pN. Hippocampal and DRG lamellipodia exerted lateral forces up to 20 pN, but lamellipodia of DRG neurons could exert a vertical force larger than that of hippocampal neurons. Force-velocity relationships (Fv) in both types of neurons had the same qualitative behaviour, consistent with a common autocatalytic model of force generation. These results indicate that molecular mechanisms of force generation of GC from CNS and PNS neurons are similar but the amplitude of generated force is influenced by their cytoskeletal properties