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

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

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

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

Systems, interactions and macrotheory

A significant proportion of early HCI research was guided by one very clear vision: that the existing theory base in psychology and cognitive science could be developed to yield engineering tools for use in the interdisciplinary context of HCI design. While interface technologies and heuristic methods for behavioral evaluation have rapidly advanced in both capability and breadth of application, progress toward deeper theory has been modest, and some now believe it to be unnecessary. A case is presented for developing new forms of theory, based around generic “systems of interactors.” An overlapping, layered structure of macro- and microtheories could then serve an explanatory role, and could also bind together contributions from the different disciplines. Novel routes to formalizing and applying such theories provide a host of interesting and tractable problems for future basic research in HCI

Oral dosing with papaya latex is an effective anthelmintic treatment for sheep infected with Haemonchus contortus

Background The cysteine proteinases in papaya latex have been shown to have potent anthelmintic properties in monogastric hosts such as rodents, pigs and humans, but this has not been demonstrated in ruminants. Methods In two experiments, sheep were infected concurrently with 5,000 infective larvae of Haemonchus contortus and 10,000 infective larvae of Trichostrongylus colubriformis and were then treated with the supernatant from a suspension of papaya latex from day 28 to day 32 post-infection. Faecal egg counts were monitored from a week before treatment until the end of the experiment and worm burdens were assessed on day 35 post-infection. Results We found that the soluble fraction of papaya latex had a potent in vivo effect on the abomasal nematode H. contortus, but not on the small intestinal nematode T. colubriformis. This effect was dose-dependent and at tolerated levels of gavage with papaya latex (117 μmol of active papaya latex supernatant for 4 days), the H. contortus worm burdens were reduced by 98%. Repeated treatment, daily for 4 days, was more effective than a single dose, but efficacy was not enhanced by concurrent treatment with the antacid cimetidine. Conclusions Our results provide support for the idea that cysteine proteinases derived from papaya latex may be developed into novel anthelmintics for the treatment of lumenal stages of gastro-intestinal nematode infections in sheep, particularly those parasitizing the abomasum

Artificial intelligence for dementia drug discovery and trials optimization

Drug discovery and clinical trial design for dementia have historically been challenging. In part these challenges have arisen from patient heterogeneity, length of disease course, and the tractability of a target for the brain. Applying big data analytics and machine learning tools for drug discovery and utilizing them to inform successful clinical trial design has the potential to accelerate progress. Opportunities arise at multiple stages in the therapy pipeline and the growing availability of large medical data sets opens possibilities for big data analyses to answer key questions in clinical and therapeutic challenges. However, before this goal is reached, several challenges need to be overcome and only a multi‐disciplinary approach can promote data‐driven decision‐making to its full potential. Herein we review the current state of machine learning applications to clinical trial design and drug discovery, while presenting opportunities and recommendations that can break down the barriers to implementation