Comparisons of trace constituents from ground stations and the DC-8 aircraft during PEM-West B

Chemical data from ground stations in Asia and the North Pacific are compared with data from the DC-8 aircraft collected during the Pacific Exploratory Measurements in the Western Pacific Ocean (PEM-West B) mission. Ground station sampling took place on Hong Kong, Taiwan, Okinawa, and Cheju; and at three Pacific islands, Shemya, Midway, and Oahu. Aircraft samples were collected during 19 flights, most over the western North Pacific. Aluminum was used as an indicator of mineral aerosol, and even though the aircraft did sample Asian dust, strong dust storms were not encountered. The frequency distribution for non-sea-salt sulfate (nss SO4=) in the aircraft samples was bimodal: the higher concentration mode (∼1 μg m−3) evidently originated from pollution or, less likely, from volcanic sources, while the lower mode, with a peak at 0.040 μg m−3, probably was a product of biogenic emissions. In addition, the concentrations of aerosol sulfate varied strongly in the vertical: arithmetic mean SO4=concentrations above 5000 m ( = 0.21±0.69 μg m−3) were substantially lower than those below ( = 1.07±0.87 μg m−3), suggesting the predominance of the surface sources. Several samples collected in the stratosphere exhibited elevated SO4=, however, probably as a result of emissions from Mount Pinatubo. During some boundary layer legs on the DC-8, the concentrations of CO and O3 were comparable to those of clean marine air, but during other legs, several chemically distinct air masses were sampled, including polluted air in which O3was photochemically produced. In general, the continental outflow sampled from the aircraft was substantially diluted with respect to what was observed at the ground stations. Higher concentrations of aerosol species, O3, and CO at the Hong Kong ground station relative to the aircraft suggest that much of the continental outflow from southeastern Asia occurs in the lower troposphere, and extensive long-range transport out of this part of Asia is not expected. In comparison, materials emitted farther to the north apparently are more susceptible to long-range transport

Estimation of the atmospheric flux of nutrients and trace metals to the Eastern Tropical North Atlantic Ocean

Atmospheric deposition contributes potentially significant amounts of the nutrients iron, nitrogen and phosphorus (via mineral dust and anthropogenic aerosols) to the oligotrophic tropical North Atlantic Ocean. Transport pathways, deposition processes and source strengths contributing to this atmospheric flux are all highly variable in space and time. Atmospheric sampling was conducted during 28 research cruises through the Eastern Tropical North Atlantic (ETNA) over a 12 year period and a substantial dataset of measured concentrations of nutrients and trace metals in aerosol and rainfall over the region was acquired. This database was used to quantify (on a spatial- and seasonal-basis) the atmospheric input of ammonium, nitrate, soluble phosphorus and soluble and total iron, aluminium and manganese to the ETNA. The magnitude of atmospheric input varies strongly across the region, with high rainfall rates associated with the Inter-tropical Convergence Zone contributing to high wet deposition fluxes in the south, particularly for soluble species. Dry deposition fluxes of species associated with mineral dust exhibited strong seasonality, with highest fluxes associated with winter-time low-level transport of Saharan dust. Overall (wet plus dry) atmospheric inputs of soluble and total trace metals were used to estimate their soluble fractions. These also varied with season and were generally lower in the dry north than in the wet south. The ratio of ammonium plus nitrate to soluble iron in deposition to the ETNA was lower than the N:Fe requirement for algal growth in all cases, indicating the importance of the atmosphere as a source of excess iron

Recapitulating Parkinson's disease pathology in a three-dimensional human neural cell culture model.

Extensive loss of dopaminergic neurons, and aggregation of the protein α-synuclein into ubiquitin-positive Lewy bodies represents a major neuropathological hallmark of Parkinson's disease. At present the generation of large nuclear-associated Lewy bodies from endogenous wild-type α-synuclein, translationally regulated under its own promoter in human cell culture models requires costly and time-consuming protocols. Here, we demonstrate that fully differentiated human SH-SY5Y neuroblastoma cells grown in three-dimensional cell culture develop Lewy body-like pathology upon exposure to exogenous α-synuclein species. In contrast to most cell- and rodent-based models that exhibit multiple diffuse α-synuclein aggregates throughout the cytoplasm, a single large nuclear inclusion immuno-positive for α-synuclein and ubiquitin is rapidly obtained in our model. This was achieved, without the need for over-expression of α-synuclein or genetic modification of the cell line. However, phosphorylation of α-synuclein within these inclusions was not observed. The system described here provides an ideal tool to screen compounds to therapeutically intervene in Lewy body formation and to investigate the mechanisms involved in disease progression in synucleinopathies

Cortical AAV-CNTF gene therapy combined with intraspinal mesenchymal precursor cell transplantation promotes functional and morphological outcomes after spinal cord injury in adult rats

Ciliary neurotrophic factor (CNTF) promotes survival and enhances long-distance regeneration of injured axons in parts of the adult CNS. Here we tested whether CNTF gene therapy targeting corticospinal neurons (CSN) in motor-related regions of the cerebral cortex promotes plasticity and regrowth of axons projecting into the female adult F344 rat spinal cord after moderate thoracic (T10) contusion injury (SCI). Cortical neurons were transduced with a bicistronic adeno-associated viral vector (AAV1) expressing a secretory form of CNTF coupled to mCHERRY (AAV-CNTFmCherry) or with control AAV only (AAV-GFP) two weeks prior to SCI. In some animals, viable or nonviable F344 rat mesenchymal precursor cells (rMPCs) were injected into the lesion site two weeks after SCI to modulate the inhibitory environment. Treatment with AAV-CNTFmCherry, as well as with AAV-CNTFmCherry combined with rMPCs, yielded functional improvements over AAV-GFP alone, as assessed by open-field and Ladderwalk analyses. Cyst size was significantly reduced in the AAV-CNTFmCherry plus viable rMPC treatment group. Cortical injections of biotinylated dextran amine (BDA) revealed more BDA-stained axons rostral and alongside cysts in the AAV-CNTFmCherry versus AAV-GFP groups. After AAV-CNTFmCherry treatments, many sprouting mCherry-immunopositive axons were seen rostral to the SCI, and axons were also occasionally found caudal to the injury site. These data suggest that CNTF has the potential to enhance corticospinal repair by transducing parent CNS populations

The anthelmintic efficacy of plant-derived cysteine proteinases against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, in vivo

Gastrointestinal (GI) nematodes are important disease-causing organisms, controlled primarily through treatment with synthetic drugs, but the efficacy of these drugs has declined due to widespread resistance, and hence new drugs, with different modes of action, are required. Some medicinal plants, used traditionally for the treatment of worm infections, contain cysteine proteinases known to damage worms irreversibly in vitro. Here we (i) confirm that papaya latex has marked efficacy in vivo against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, (ii) demonstrate the dosedependent nature of the activity (>90% reduction in egg output and 80% reduction in worm burden at the highest active enzyme concentration of 133 nmol), (iii) establish unequivocally that it is the cysteine proteinases that are the active principles in vivo (complete inhibition of enzyme activity when pre-incubated with the cysteine proteinase-specific inhibitor, E-64) and (iv) show that activity is confined to worms that are in the intestinal lumen. The mechanism of action was distinct from all current synthetic anthelmintics, and was the same as that in vitro, with the enzymes attacking and digesting the protective cuticle. Treatment had no detectable side-effects on immune cell numbers in the mucosa (there was no difference in the numbers of mast cells and goblet cells between the treated groups) and mucosal architecture (length of intestinal villi). Only the infected and untreated mice had much shorter villi than the other 3 groups, which was a consequence of infection and not treatment. Plant-derived cysteine proteinases are therefore prime candidates for development as novel drugs for the treatment of GI nematode infections

Microwave-assisted in situ laser dye incorporation into high sensitivity whispering gallery mode microresonators

Optical whispering gallery mode microresonators (WGM-μRs) are powerful sensitive components with many analytical applications. Here, spherical WGM-μRs have been synthesised in a single-step microwave (MW)-assisted heterophase polymerisation. The microresonators are based on poly(styrene) beads into which the organic lasing dye nile red was incorporated as gain medium in situ during the polymerisation. The particle diameter and diameter distribution of the synthesised particles were tuned in the range of around 200 nm up to 50 μm by adjusting the concentration between stabiliser poly-(N-vinyl pyrrolidone) (PVP) and monomer styrene, and the solvent composition in the dispersion process. Lower water content enabled the synthesis of spherical particles with large size polydispersity, from which WGM-μRs with a variety of diameters were selected. Microspheres with diameters ≳3.5 μm supported WGMs. The WGMs were excited through free space via the fluorescence of the laser dye. Pumping power levels <1 μW were sufficient to excite WGMs. WGM shifts of beads with diameter between ≈5 and 30 μm measured in air and water show a sensitivity up to 54 nm/RIU for the smallest particles. Dye doped WGM-μR in the low μm size range obtained by the MW-assisted polymerisation process with its versatility, low processing times and high yields opens new horizons for the applications of these systems as sensors

Past, present and future atmospheric nitrogen deposition

Reactive nitrogen emissions into the atmosphere are increasing due to human activities, affecting nitrogen deposition to the surface and impacting the productivity of terrestrial and marine ecosystems. An atmospheric chemistry-transport model (TM4-ECPL) is here used to calculate the global distribution of total nitrogen deposition, accounting for the first time for both its inorganic and organic fractions in gaseous and particulate phases, and past and projected changes due to anthropogenic activities. The anthropogenic and biomass burning ACCMIP historical and RCP6.0 and RCP8.5 emissions scenarios are used. Accounting for organic nitrogen (ON) primary emissions, the present-day global nitrogen atmospheric source is about 60% anthropogenic, while total N deposition increases by about 20% relative to simulations without ON primary emissions. About 20-25% of total deposited N is ON. About 10% of the emitted nitrogen oxides are deposited as ON instead of inorganic nitrogen (IN) as is considered in most global models. Almost a 3-fold increase over land (2-fold over the ocean) has been calculated for soluble N deposition due to human activities from 1850 to present. The investigated projections indicate significant changes in the regional distribution of N deposition and chemical composition, with reduced compounds gaining importance relative to oxidized ones, but very small changes in the global total flux. Sensitivity simulations quantify uncertainties due to the investigated model parameterizations of IN partitioning onto aerosols and of N chemically fixed on organics to be within 10% for the total soluble N deposition and between 25-35% for the dissolved ON deposition. Larger uncertainties are associated with N emissions

Automating the Semantic Mapping between Regulatory Guidelines and Organizational Processes

The mapping of regulatory guidelines with organizational processes is an important aspect of a regulatory compliance management system. Automating this mapping process can greatly improve the overall compliance process. Currently, there is research on mapping between different entities such as ontology mapping, sentence similarity, semantic similarity and regulation-requirement mapping. However, there has not been adequate research on the automation of the mapping process between regulatory guidelines and organizational processes. In this paper, we explain how Natural Language Processing and Semantic Web technologies can be applied in this area. In particular, we explain how we can take advantage of the structures of regulation-ontology and the process-ontology in order to compute the similarity between a regulatory guideline and a process. Our methodology is validated using a case study in the Pharmaceutical industry, which has shown promising results

Human factors and data logging processes with the use of advanced technology for adults with type 1 diabetes (T1DM): A systematic integrative review

Background: People with T1DM are confronted with self-management tasks and strategies to reduce risks of long-term complications against the risk of hypoglycemic events. The potential of advanced and evolving technology to address these issues involves consideration of psychological and behavioral constructs alongside the usability of devices. Access and uptake of advanced technology is further influenced by economic factors and health care provider capacity to support such interventions. Previous reviews have focused upon either clinical outcomes or descriptively scoped the literature or have synthesized studies on adults with children and young people where human factors are different. Objective: The objective of this review was to describe the relationship between human factors and adherence with technology for data logging processes in adults (> 18 years) with T1DM and to explore the factors which influence this association. Methods: A systematic literature review. Results: 18 studies were included in the review following a literature search using the PRISMA guidelines and a quality appraisal process. This included 3320 participants with a mean age of 42 years. Overall, adults felt more satisfied with their treatment on transition to advanced technology (insulin pump and CGM), the most significant contributing factor was when BG levels were consistently < 7.00mmol/l (P =.009). However, participants spent considerable time on their diabetes self-care. There was evidence that logging of data was positively correlated with increasing age with the use of an app that provided meaningful feedback (regression coefficient = 55.8 recordings/ year; P = 0.009). Furthermore, there were benefits of CGM use for older adults in mediating complexities and their fears of hypoglycemia with reported significant differences in well-being (P= .009). Qualitative studies within the review aimed to explore the use and uptake of technology within the context of everyday lives. Participants experienced ‘frustrations’ with CGM, CSII, calibration of devices and alarms. In addition, there were implications for ‘body image’ when carrying and using a device. This takes into account wide variations in individual use and interaction with technology across a continuum of sociocultural contexts. This has implications for the way in which future technologies are designed. Conclusions: Many of the quantitative studies in the review were limited by small sample sizes. This may make it difficult to generalize findings to other contexts. This is further limited by a sample that was predominantly Caucasian, well-controlled and engaged with their self-care. However, the use of critical appraisal frameworks has highlighted areas where research into human factors and data logging processes of individuals could be improved. This includes engaging people in the design of the technology, and further exploration of the way in which significant others impact on the behavior and attitude of the individual towards technology use