Chemical data assimilation estimates of continental U.S. ozone and nitrogen budgets during the Intercontinental Chemical Transport Experiment-North America

Global ozone analyses, based on assimilation of stratospheric profile and ozone column measurements, and NOy predictions from the Real-time Air Quality Modeling System (RAQMS) are used to estimate the ozone and NOy budget over the continental United States during the July-August 2004 Intercontinental Chemical Transport Experiment-North America (INTEX-A). Comparison with aircraft, satellite, surface, and ozonesonde measurements collected during INTEX-A show that RAQMS captures the main features of the global and continental U.S. distribution of tropospheric ozone, carbon monoxide, and NOy with reasonable fidelity. Assimilation of stratospheric profile and column ozone measurements is shown to have a positive impact on the RAQMS upper tropospheric/lower stratosphere ozone analyses, particularly during the period when SAGE III limb scattering measurements were available. Eulerian ozone and NOy budgets during INTEX-A show that the majority of the continental U.S. export occurs in the upper troposphere/lower stratosphere poleward of the tropopause break, a consequence of convergence of tropospheric and stratospheric air in this region. Continental U.S. photochemically produced ozone was found to be a minor component of the total ozone export, which was dominated by stratospheric ozone during INTEX-A. The unusually low photochemical ozone export is attributed to anomalously cold surface temperatures during the latter half of the INTEX-A mission, which resulted in net ozone loss during the first 2 weeks of August. Eulerian NOy budgets are shown to be very consistent with previously published estimates. The NOy export efficiency was estimated to be 24%, with NOx + PAN accounting for 54% of the total NOy export during INTEX-A. Copyright 2007 by the American Geophysical Union

High pressure induced precipitation in Al7075 alloy

Precipitate-matrix interactions govern the mechanical behavior of precipitate strengthened Al-based alloys. These alloys find a wide range of applications ranging from aerospace to automobile and naval industries due to their low cost and high strength to weight ratio. Structures made from Al-based alloys undergo complex loading conditions such as high strain rate impact, which involves high pressures. Here we use diamond anvil cells to study the behavior of Al-based Al7075 alloy under quasi-hydrostatic and non-hydrostatic pressure up to ~53 GPa. In situ X-ray diffraction (XRD) and pre- and post-compression transmission electron microscopy (TEM) imaging are used to analyze microstructural changes and estimate high pressure strength. We find a bulk modulus of 75.2 +- 1.9 GPa using quasi-hydrostatic pressure XRD measurements. XRD showed that non-hydrostatic pressure leads to a significant increase in defect density and peak broadening with pressure cycling. XRD mapping under non-hydrostatic pressure revealed that the region with the highest local pressure had the greatest increase in defect nucleation, whereas the region with the largest local pressure gradient underwent texturing and had larger grains. TEM analysis showed that pressure cycling led to the nucleation and growth of many precipitates. The significant increase in defect and precipitate density leads to an increase in strength for Al7075 alloy at high pressures.Comment: 15 pages, 5 figure

Proteomic Analysis of Saliva from Patients with Oral Chronic Graft-Versus-Host Disease

AbstractChronic graft-versus-host disease (cGVHD) is an immune-mediated disorder and is the major long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The oral mucosa, including the salivary glands, is affected in the majority of patients with cGVHD; however, at present there is only a limited understanding of disease pathobiology. In this study, we performed a quantitative proteomic analysis of saliva pooled from patients with and without oral cGVHD—cGVHD(+) and cGVHD(−), respectively—using isobaric tags for relative and absolute quantification labeling, followed by tandem mass spectrometry. Among 249 salivary proteins identified by tandem mass spectrometry, 82 exhibited altered expression in the oral cGVHD(+) group compared with the cGVHD(−) group. Many of the identified proteins function in innate or acquired immunity, or are associated with tissue maintenance functions, such as proteolysis or the cytoskeleton. Using ELISA immunoassays, we further confirmed that 2 of these proteins, IL-1 receptor antagonist and cystatin B, showed decreased expression in patients with active oral cGVHD (P < .003). Receiver operating curve characteristic analysis revealed that these 2 markers were able to distinguish oral cGVHD with a sensitivity of 85% and specificity of 60%, and showed slightly better discrimination in newly diagnosed patients evaluated within 12 months of allo-HSCT (sensitivity, 92%; specificity 73%). In addition to identifying novel potential salivary cGVHD biomarkers, our study demonstrates that there is coordinated regulation of protein families involved in inflammation, antimicrobial defense, and tissue protection in oral cGVHD that also may reflect changes in salivary gland function and damage to the oral mucosa

Tumor Cell-Surface Binding of Immune Stimulating Polymeric Glyco-Adjuvant via Cysteine-Reactive Pyridyl Disulfide Promotes Antitumor Immunity

Immune stimulating agents like Toll-like receptor 7 (TLR7) agonists induce potent antitumor immunity but are limited in their therapeutic window due to off-target immune activation. Here, we developed a polymeric delivery platform that binds excess unpaired cysteines on tumor cell surfaces and debris to adjuvant tumor neoantigens as an in situ vaccine. The metabolic and enzymatic dysregulation in the tumor microenvironment produces these exofacial free thiols, which can undergo efficient disulfide exchange with thiol-reactive pyridyl disulfide moieties upon intratumoral injection. These functional monomers are incorporated into a copolymer with pendant mannose groups and TLR7 agonists to target both antigen and adjuvant to antigen presenting cells. When tethered in the tumor, the polymeric glyco-adjuvant induces a robust antitumor response and prolongs survival of tumor-bearing mice, including in checkpoint-resistant B16F10 melanoma. The construct additionally reduces systemic toxicity associated with clinically relevant small molecule TLR7 agonists

World radiocommunication conference 12 : implications for the spectrum eco-system

Spectrum allocation is once more a key issue facing the global telecommunications industry. Largely overlooked in current debates, however, is the World Radiocommunication Conference (WRC). Decisions taken by WRC shape the future roadmap of the telecommunications industry, not least because it has the ability to shape the global spectrum allocation framework. In the debates of WRC-12 it is possible to identify three main issues: enhancement of the international spectrum regulatory framework, regulatory measures required to introduce Cognitive Radio Systems (CRS) technologies; and, additional spectrum allocation to mobile service. WRC-12 eventually decided not to change the current international radio regulations with regard to the first two issues and agreed to the third issue. The main implications of WRC-12 on the spectrum ecosystem are that most of actors are not in support of the concept of spectrum flexibility associated with trading and that the concept of spectrum open access is not under consideration. This is explained by the observation that spectrum trading and spectrum commons weaken state control over spectrum and challenge the main principles and norms of the international spectrum management regime. In addition, the mobile allocation issue has shown the lack of conformity with the main rules of the regime: regional spectrum allocation in the International Telecommunication Union (ITU) three regions, and the resistance to the slow decision making procedures. In conclusion, while the rules and decision-making procedures of the international spectrum management regime were challenged in the WRC-12, the main principles and norms are still accepted by the majority of countries

With or without force? : European public opinion on democracy promotion

A Large part of the education provided at colleges and universities of today requires for thestudent to be more independent in their studies. This demands that the physical space,where the students choose to study, is designed in a way that can encourage and supportlearning. It seems as though that many of the learning spaces of today don’t always meetthe students’ needs. The university library at the University of Umeå is currently planningto design new learning spaces for the students. The aim of this study is to examine how thephysical learning space can be designed to engage and encourage the students in theirlearning process. Based on literature describing learning spaces we have initially identified three mainareas to examine- Learning, Information Technology and Learning space design. Theseareas are all important features in the design of new learning spaces. With informationdrawn from that literature we conducted an empirical study at the library of the Universityof Umeå. The empirical study was carried out through observations and focus groupinterviews. To give us more insight about the students’ thoughts about the learning spacewe also compared our findings with a survey conducted by the library personnel in 2008and 2010. The result of our study shows that there are some areas to be improved in theexisting learning space. The students are working more collaboratively which requiresmore group areas. Our study also shows that flexibility, more student interaction and asocial and engaging environment are all important features in the design of new learningspaces

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

Measuring access to primary care appointments: a review of methods

BACKGROUND: Patient access to primary care appointments is not routinely measured despite the increasing interest in this aspect of practice activity. The generation of standardised data (or benchmarks) for access could inform developments within primary care organisations and act as a quality marker for clinical governance. Logically the setting of targets should be based on a sound system of measurement. The practicalities of developing appropriate measures need debate. Therefore we aimed to search for and compare methods that have been published or are being developed to measure patient access to primary care appointments, with particular focus on finding methods using appointment system data. METHOD: A search and review was made of the primary care literature from 1990 to 2001, which included an assessment of online resources (websites) and communication with recognised experts. The identified methods were assessed. RESULTS: The published literature in this specific area was not extensive but revealed emerging interest in the late 1990s. Two broad approaches to the measurement of waiting times to GP appointments were identified. Firstly, appointment systems in primary care organisations were analysed in differing ways to provide numerical data and, secondly, patient perceptions (reports) of access were evaluated using survey techniques. Six different methods were found which were based on appointment systems data. CONCLUSION: The two approaches of either using patient questionnaires or appointment system data are methods that represent entirely different aims. The latter method when used to represent patient waiting times for 'routine' elective appointments seems to hold promise as a useful tool and this avoids the definitional problems that surround 'urgent' appointments. The purpose for which the data is being collected needs to be borne in mind and will determine the chosen methods of data retrieval and representation