Search

Objective We outline our vision for a 14 Tesla MR system. This comprises a novel whole-body magnet design utilizing high temperature superconductor; a console and associated electronic equipment; an optimized radiofrequency coil setup for proton measurement in the brain, which also has a local shim capability; and a high-performance gradient set. Research fields The 14 Tesla system can be considered a ‘mesocope’: a device capable of measuring on biologically relevant scales. In neuroscience the increased spatial resolution will anatomically resolve all layers of the cortex, cerebellum, subcortical structures, and inner nuclei. Spectroscopic imaging will simultaneously measure excitatory and inhibitory activity, characterizing the excitation/inhibition balance of neural circuits. In medical research (including brain disorders) we will visualize fine-grained patterns of structural abnormalities and relate these changes to functional and molecular changes. The significantly increased spectral resolution will make it possible to detect (dynamic changes in) individual metabolites associated with pathological pathways including molecular interactions and dynamic disease processes. Conclusions The 14 Tesla system will offer new perspectives in neuroscience and fundamental research. We anticipate that this initiative will usher in a new era of ultra-high-field MR.

Summary - The role of industry in being able to scale up vaccine production was crucial to the programme - Pace was also a key factor in the programme’s success - Many businesses operated at risk in order to deliver the required outcome - It is important to maintain a diversity of industrial players that can deliver globally - The networks of experts and the research institutes play a vital role in meeting these challenges.

BACKGROUNDPancreatic cancer (PaC) has poor (10%) 5-year overall survival, largely due to predominant late-stage diagnosis. Patients with new-onset diabetes (NOD) are at a six-to eightfold increased risk for PaC. We developed a pancreatic cancer detection test for the use in a clinical setting that employs a logistic regression model based on 5-hydroxymethylcytosine (5hmC) profiling of cell-free DNA (cfDNA).METHODScfDNA was isolated from plasma from 89 subjects with PaC and 596 case-control non-cancer subjects, and 5hmC libraries were generated and sequenced. These data coupled with machine-learning, were used to generate a predictive model for PaC detection, which was independently validated on 79 subjects with PaC, 163 non-cancer subjects, and 506 patients with non-PaC cancers.RESULTSThe area under the receiver operating characteristic curve for PaC classification was 0.93 across the training data. Training sensitivity was 58.4% (95% confidence interval [CI]: 47.5– 68.6) after setting a classification probability threshold that resulted in 98% (95% CI: 96.5–99) specificity. The independent validation dataset sensitivity and specificity were 51.9% (95% CI: 40.4–63.3) and 100.0% (95% CI: 97.8–100.0), respectively. Early-stage (stage 1 and 2) PaC detection was 47.6% (95% CI: 23%–58%) and 39.4% (95% CI: 32%–64%) in the training and independent validation datasets, respectively. Sensitivity and specificity in NOD patients were 55.2% [95% CI: 35.7–73.6] and 98.4% [95% CI: 91.3–100.0], respectively. The PaC signal was identified in intraductal papillary mucinous neoplasm (64%), pancreatitis (56%), and non-PaC cancers (17%).CONCLUSIONSThe pancreatic cancer detection assay showed robust performance in the tested cohorts and carries the promise of becoming an essential clinical tool to enable early detection in high-risk NOD patients.

The Salton Sea Basin in California suffers from poor air quality, and an expanding dry lakebed (playa) presents a new potential dust source. In 2017-18, depositing dust was collected approximately monthly at five sites in the Salton Sea Basin and analyzed for total elemental and soluble anion content. These data were analyzed with Positive Matrix Factorization (PMF). The PMF method resolved seven dust sources with distinct compositional markers: Playa (Mg, SO42-, Na, Ca, Sr), Colorado Alluvium (U, Ca), Local Alluvium (Al, Fe, Ti), Agricultural Burning (K, PO43-), Sea Spray (Na, Cl-, Se), Anthropogenic Trace Metals (Sb, As, Zn, Cd, Pb, Na), and Anthropogenic Copper (Cu). All sources except Local Alluvium are influenced or caused by current or historic anthropogenic activities. PMF attributed 55 to 80% of the measured dust flux to these six sources. The dust fluxes at the site where the playa source was dominant (89 g m-2 yr-1) were less than, but approaching the scale of, those observed at Owens Lake playas in the late 20th century. Playa emissions in the Salton Sea region were most intense during the late spring to early summer and contain high concentrations of evaporite mineral tracers, particularly Mg, Ca, and SO42-.

The authors acknowledge funding support from the NSF FESD and Earth-Life Transitions programs (T.L.), the NASA Astrobiology Institute under Cooperative Agreement No. NNA15BB03A issued through the Science Mission Directorate (T.L.), the key project of the Natural Science Foundation of China (C.-F.C.) (No. 41730424), and the program of China Scholarships Council (Y.C.) (No. 201504910582). Nitrogen and carbon isotope analyses were funded by startup funds from Virginia Tech to B.C.G. The Ediacaran-Cambrian transition is characterized by the evolution of complex eukaryotes and rapid diversification of metazoans. However, linkages between environmental triggers and evolutionary patterns remain unclear. Here, we present high-resolution records of carbon and nitrogen isotopic data (δ13C, δ15N) for a drill core extending from the early Ediacaran Doushantuo Formation to the early Cambrian Jiumenchong Formation, located on the slope of the Yangtze Block. Our data show that sedimentary bulk nitrogen isotope values (δ15Nbulk) decrease progressively from the early Ediacaran to the early Cambrian, broadly concurrent with nitrogen isotope data from other sections throughout the Yangtze Block. During the early Ediacaran, however, δ15Nbulk values from our study are higher (maximum 11.2‰) compared to those from more restricted coeval sections, suggesting a higher degree of denitrification in our slope section. The early Ediacaran δ15Nbulk data from the Yangtze Block may thus provide indirect evidence for an upwelling system that led to a shallower redoxcline in slope environments of the Upper Yangtze region. Widespread light δ15Nbulk values from the early Cambrian (minimum −7.5‰) paired with excess silicate-bound nitrogen throughout much of the Yangtze Block are most parsimoniously interpreted as non-quantitative assimilation of ammonium (NH4+) with relatively high concentrations of NH4+ accumulating in the deep basin. Overall, the spatial and temporal trends in nitrogen cycling across the Yangtze Block suggest that fixed nitrogen was more bioavailable in the Ediacaran-Cambrian Yangtze Basin compared to previously studied Mesoproterozoic sections, although nitrogen speciation in the photic zone may have varied with time. Environmental factors such as oxygen levels and nitrogen bioavailability may have shaped the evolutionary trajectory of life on the Yangtze Block and potentially elsewhere across the Ediacaran-Cambrian transition. Postprint

ObjectivesTo determine if urinary biomarkers of effect and potential harm are elevated in electronic cigarette users compared with non-smokers and if elevation correlates with increased concentrations of metals in urine.Study design and settingThis was a cross-sectional study of biomarkers of exposure, effect and potential harm in urine from non-smokers (n=20), electronic cigarette users (n=20) and cigarette smokers (n=13). Participant’s screening and urine collection were performed at the Roswell Park Comprehensive Cancer Center, and biomarker analysis and metal analysis were performed at the University of California, Riverside.ResultsMetallothionein was significantly elevated in the electronic cigarette group (3761±3932 pg/mg) compared with the non-smokers (1129±1294 pg/mg, p=0.05). 8-OHdG (8-hydroxy-2′-deoxyguanosine) was significantly elevated in electronic cigarette users (442.8±300.7 ng/mg) versus non-smokers (221.6±157.8 ng/mg, p=0.01). 8-Isoprostane showed a significant increase in electronic cigarette users (750.8±433 pg/mg) versus non-smokers (411.2±287.4 pg/mg, p=0.03). Linear regression analysis in the electronic cigarette group showed a significant correlation between cotinine and total metal concentration; total metal concentration and metallothionein; cotinine and oxidative DNA damage; and total metal concentration and oxidative DNA damage. Zinc was significantly elevated in the electronic cigarette users (584.5±826.6 µg/g) compared with non-smokers (413.6±233.7 µg/g, p=0.03). Linear regression analysis showed a significant correlation between urinary zinc concentration and 8-OHdG in the electronic cigarette users.ConclusionsThis study is the first to investigate biomarkers of potential harm and effect in electronic cigarette users and to show a linkage to metal exposure. The biomarker levels in electronic cigarette users were similar to (and not lower than) cigarette smokers. In electronic cigarette users, there was a link to elevated total metal exposure and oxidative DNA damage. Specifically, our results demonstrate that zinc concentration was correlated to oxidative DNA damage.

This work was supported at the University of California, Riverside by the NSF-EAR FESD Program and the NASA Astrobiology Institute under Cooperative Agreement No. NNA15BB03A issued through the Science Mission Directorate. We thank Roger Buick (UW) for financial support of the carbon and nitrogen isotope work. EES acknowledges support from a NASA postdoctoral fellowship, as well as valuable discussions about the Newark basin with Charlotte B. Schreiber. GDL thanks the Agouron Institute for providing funding for the Waters Autospec GC-MS instrument at UCR. It is widely agreed that the Earth’s atmosphere and oceans have undergone major redox changes over the last 2.5 billion years. However, the magnitude of these shifts remains a point of debate because it is difficult to reconstruct concentrations of dissolved O2 from indirect proxies in sedimentary archives. In this study, we show that an additional complicating factor that is rarely considered may be the pH of the water column. We analyzed rock samples from the early Jurassic Towaco Formation in the Newark basin (eastern USA), comprising deposits of a rift lake that became temporarily redox stratified. New biomarker evidence points to increasingly saline aquatic conditions during the second half of the lake’s history, with a salinity stratification that induced redox stratification, including evidence for water column anoxia, and that state may also explain the disappearance of macrofauna at this time. Distinctive lipid biomarker assemblages and stable nitrogen isotope data support previous mineralogical indications that the lake was alkaline (pH ≥ 9) during its saline episode. Despite the biomarker and macrofaunal evidence for anoxia, ratios of Fe/Al and FeHR/FeT show only small to no enrichments in the anoxic horizon compared to oxic facies in the same section – counter to what is commonly observed in anoxic marine settings. Molybdenum, As, V, U and to some degree Cd show enrichments in the anoxic interval, whereas Co, Ni, Cu, Zn and Cr do not. These patterns are most parsimoniously explained by differential pH effects on the solubility of these elements. Extrapolating from these observations in lacustrine strata, we speculate that a secular increase in seawater pH over Earth’s history as recently proposed may have helped modulate the magnitude of trace metal enrichments in marine shales, although other factors such as atmospheric and oceanic redox likely dominated the observed enrichment patterns. Further, a decrease in the solubility of ferrous iron, a major O2 sink, with increasing pH may have contributed to ocean oxygenation. In summary, our results highlight the potential importance of pH in influencing global biogeochemical cycles for multiple elements and for the interpretation of ancient nitrogen isotope signatures. Postprint

The isotopic composition of phosphate-bound oxygen (δ 18 O PO4 ) in bioapatite (Ca 10 (PO 4 ,CO 3 ) 6 (OH,F,Cl) 2 ) is increasingly used in paleoclimatology, paleoecology, and paleoceanography studies as a proxy for environmental conditions during mineral precipitation. However, a minimum total sample size (≥ 0.5 mg to > 1 mg) required for requisite triplicate analysis can limit the spatial and temporal application of the proxy, in particular in studies using microfossils (e.g., conodonts) for δ 18 O PO4 analysis. Here we present a systematically evaluated extraction-conversion-analysis protocol for conodont δ 18 O PO4 of total sample mass as small as 0.3 mg while maintaining standard analytical precision (~0.3‰, 1σ). These results were produced by systematic testing of existing methodologies in combination with the vario PYRO cube high-temperature pyrolysis system. Our data indicate that bulk carbonate samples dissolved in 7% acetic acid buffered to a pH of 3.6 provide the highest conodont yields while minimizing bioapatite etching, thus avoiding potential oxygen isotope fractionation due to selective dissolution of conodont material. Isolating phosphate from the other components of dissolved bioapatite using a highly buffered silver amine solution produces larger silver phosphate crystals and greater phosphate yields compared to the standard silver amine protocol. Analysis of silver phosphate using a high-temperature pyrolysis system with reverse helium flushing and a thermodynamic carbon monoxide trap generates reproducible δ 18 O values (0.1 to ≤ 0.4‰, 1σ) on atypically small bioapatite samples (0.3 mg). Application of this refined technique to Middle Pennsylvanian age conodonts from Arrow Canyon, NV, demonstrates the potential of the conodont δ 18 O PO4 proxy for high temporal resolution (sub-10 4 -yr) studies. Further, we propose a δ 18 O PO4 methodology to serve as a community standard that will permit more effective inter-dataset comparisons by limiting the potential influence of methodological variability on δ 18 O PO4 values.

To improve estimates of the extent of ocean oxygenation during the late Ediacaran Period, we measured the U and Mo isotope compositions of euxinic (anoxic and sulfidic) organic-rich mudrocks (ORM) of Member IV, upper Doushantuo Formation, South China. The average δ 238 U of most samples is 0.24 ± 0.16‰ (2SD; relative to standard CRM145), which is slightly higher than the average δ 238 U of 0.02 ± 0.12‰ for restricted Black Sea (deep-water Unit I) euxinic sediments and is similar to a modeled δ 238 U value of 0.2‰ for open ocean euxinic sediments in the modern well-oxygenated oceans. Because 238 U is preferentially removed to euxinic sediments compared to 235 U, expanded ocean anoxia will deplete seawater of 238 U relative to 235 U, ultimately leading to deposition of ORM with low δ 238 U. Hence, the high δ 238 U of Member IV ORM points to a common occurrence of extensive ocean oxygenation ca. 560 to 551 Myr ago. The Mo isotope composition of sediments deposited from strongly euxinic bottom waters ([H 2 S] aq >11 μM) either directly records the global seawater Mo isotope composition (if Mo removal from deep waters is quantitative) or represents a minimum value for seawater (if Mo removal is not quantitative). Near the top of Member IV, δ 98 Mo approaches the modern seawater value of 2.34 ± 0.10‰. High δ 98 Mo points to widespread ocean oxygenation because the preferential removal of isotopically light Mo to sediments occurs to a greater extent in O 2 -rich compared to O 2 -deficient marine environments. However, the δ 98 Mo value for most Member IV ORM is near 0‰ (relative to standard NIST SRM 3134 = 0.25‰), suggesting extensive anoxia. The low δ 98 Mo is at odds with the high Mo concentrations of Member IV ORM, which suggest a large seawater Mo inventory in well-oxygenated oceans, and the high δ 238 U. Hence, we propose that the low δ 98 Mo of most Member IV ORM was fractionated from contemporaneous seawater. Possible mechanisms driving this isotope fractionation include: (1) inadequate dissolved sulfide for quantitative thiomolybdate formation and capture of a seawater-like δ 98 Mo signature in sediments or (2) delivery of isotopically light Mo to sediments via a particulate Fe–Mn oxyhydroxide shuttle. A compilation of Mo isotope data from euxinic ORM suggests that there were transient episodes of extensive ocean oxygenation that break up intervals of less oxygenated oceans during late Neoproterozoic and early Paleozoic time. Hence, Member IV does not capture irreversible deep ocean oxygenation. Instead, complex ocean redox variations likely marked the transition from O 2 -deficient Proterozoic oceans to widely oxygenated later Phanerozoic oceans.

The late Neoproterozoic Era was characterized by dramatic transitions in climate, including Snowball Earth glaciation, and in the increasing oxygenation state of the atmosphere and oceans. However, late Neoproterozoic glacial deposits are poorly documented in North China. To better understand the Neoproterozoic glacial events in North China, we investigated five sections along a north-south transect across the Helan Mountains capturing a transition from shelf margin to intrashelf basin. This effort revealed an excellent exposure of Neoproterozoic diamictite and associated carbonate succession (Zhengmuguan Formation) on the western shelf margin of North China. Sedimentary features in the diamictite indicate that it might be a glacial sequence partially influenced by sediment gravity flows, with values for the Chemical Index of Alternation (CIA) consistent with cold, arid depositional environment. The overlying carbonate succession is sporadic, with exposures confined mostly to southern areas that disappear to the north. Identification of the Zhengmuguan sequence as a cap carbonate is based on the occurrence of distinctive attributes that are widely found in typical Neoproterozoic cap carbonates around the world. The ∼1.6-m-thick cap carbonate consists of a lower thinly laminated dolomite and an upper thick-bedded dolomite, directly overlying the top of the Zhengmuguan glacial diamictite. Based on field and petrographic observations and high-resolution geochemical analyses of major, trace, and rare earth elements; organic carbon isotopes (δ13Corg); and total organic carbon (TOC), we are able to interpret the depositional environments and the possible origin of the cap carbonate. The occurrence of late Ediacaran fossils in the overlying Tuerkeng Formation imply that the Zhengmuguan Formation is mid-late Ediacaran and thus may represent a mid-late Ediacaran glaciation. Our petrographic and geochemical results suggest the Zhengmuguan cap carbonate was initially deposited via glacial meltwater with significant inputs from continental weathering subsequently overprinted by upwelling anoxic deep seawaters along a continental margin. In summary, our data from a poorly known mid-late Ediacaran cap carbonate capture a high-resolution record of shifting climatic and oceanographic conditions of at least regional importance. The uncertainties of these interpretations are high, but the potential importance of these findings justifies the need to publish the data and our conclusions—along with the unavoidable caveats that come with any poorly dated frontier section.

© 2017 John Wiley & Sons Ltd The Athel silicilyte is an enigmatic, hundreds of meters thick, finely laminated quartz deposit, in which silica precipitated in deep water (>~100–200 m) at the Ediacaran–Cambrian boundary in the South Oman Salt Basin. In contrast, Meso-Neoproterozoic sinks for marine silica were dominantly restricted to peritidal settings. The silicilyte is known to contain sterane biomarkers for demosponges, which today are benthic, obligately aerobic organisms. However, the basin has previously been described as permanently sulfidic and time-equivalent shallow-water carbonate platform and evaporitic facies lack silica. The Athel silicilyte thus represents a unique and poorly understood depositional system with implications for late Ediacaran marine chemistry and paleoecology. To address these issues, we made petrographic observations, analyzed biomarkers in the solvent-extractable bitumen, and measured whole-rock iron speciation and oxygen and silicon isotopes. These data indicate that the silicilyte is a distinct rock type both in its sedimentology and geochemistry and in the original biology present as compared to other facies from the same time period in Oman. The depositional environment of the silicilyte, as compared to the bounding shales, appears to have been more reducing at depth in sediments and possibly bottom waters with a significantly different biological community contributing to the preserved biomarkers. We propose a conceptual model for this system in which deeper, nutrient-rich waters mixed with surface seawater via episodic mixing, which stimulated primary production. The silica nucleated on this organic matter and then sank to the seafloor, forming the silicilyte in a sediment-starved system. We propose that the silicilyte may represent a type of environment that existed elsewhere during the Neoproterozoic. These environments may have represented an important locus for silica removal from the oceans.

Recent sequencing and assembly of the genome for the fungal pathogen Candida albicans used simple automated procedures for the identification of putative genes. We have reviewed the entire assembly, both by hand and with additional bioinformatic resources, to accurately map and describe 6,354 genes and to identify 246 genes whose original database entries contained sequencing errors (or possibly mutations) that affect their reading frame. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that might be targeted for antifungal therapy. We also observed that, compared to other fungi, the protein-coding sequences in the C. albicans genome are especially rich in short sequence repeats. Finally, our improved annotation permitted a detailed analysis of several multigene families, and comparative genomic studies showed that C. albicans has a far greater catabolic range, encoding respiratory Complex 1, several novel oxidoreductases and ketone body degrading enzymes, malonyl-CoA and enoyl-CoA carriers, several novel amino acid degrading enzymes, a variety of secreted catabolic lipases and proteases, and numerous transporters to assimilate the resulting nutrients. The results of these efforts will ensure that the Candida research community has uniform and comprehensive genomic information for medical research as well as for future diagnostic and therapeutic applications., Synopsis Candida albicans is a commonly encountered fungal pathogen usually responsible for superficial infections (thrush and vaginitis). However, an estimated 30% of severe fungal infections, most due to Candida, result in death. Those who are most at risk include individuals taking immune-suppressive drugs following organ transplantation, people with HIV infection, premature infants, and cancer patients undergoing chemotherapy. Current therapies for this pathogen are made more difficult by the significant secondary effects of anti-fungal drugs that target proteins that are also found in the human host. Recent sequencing and assembly of the genome for the fungal pathogen C. albicans used simple automated procedures for the identification of putative genes. Here, we report a detailed annotation of the 6,354 genes that are present in the genome sequence of this organism, essentially writing the dictionary of the C. albicans genome. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that are absent from the human genome and whose products might be targeted for antifungal therapy. The results of these efforts will thus ensure that the Candida research community has uniform and comprehensive genomic information for medical research, for the development of functional genomic tools as well as for future diagnostic and therapeutic applications.

Wireless Mesh Networks (WMN) with multiple gateway leads to load sharing problem. Good amount of work has been done on static load distribution in WMN. But has its own limitation because of dynamic nature load. Dynamic load sharing has been the focus of this work, as very little work is done on this. IEEE 802.11s proposal is in place have protocol for dynamic load shifting from one gateway region to the other. However creating dynamic partition around each gateway remains problem of research. We in this paper have proposed and simulated enhance dynamic load balancing among the partitions. That is, Internet Gateway (called Mesh Portal Point in 802.11s) load balancing problem using a graph theory heuristic for graph partitioning. Simulation results show increased mesh throughput.

High-resolution geochemical analyses of organic-rich shale and carbonate through the 2500 million-year-old Mount McRae Shale in the Hamersley Basin of northwestern Australia record changes in both the oxidation state of the surface ocean and the atmospheric composition. The Mount McRae record of sulfur isotopes captures the widespread and possibly permanent activation of the oxidative sulfur cycle for perhaps the first time in Earth's history. The correlation of the time-series sulfur isotope signals in northwestern Australia with equivalent strata from South Africa suggests that changes in the exogenic sulfur cycle recorded in marine sediments were global in scope and were linked to atmospheric evolution. The data suggest that oxygenation of the surface ocean preceded pervasive and persistent atmospheric oxygenation by 50 million years or more.

The recent resurgence of regionalism is not Asia-specific, but part of a worldwide phenomenon. In the 1950s and 1960s the phenomenon of regionalism was particularly pronounced not only in Europe but also in Africa, the Americas and Asia and the Pacific. These early efforts were followed by a period of stagnation in region formation in the 1970s. In the 1980s and 1990s, however, there was a dramatic renewal of interest in regionalism, that shows every sign of continuing into the twenty-first century. This chapter examines how and why change to regional structures such as ASEAN, APEC, the ASEAN Regional Forum and the Asian Development Bank is occurring.

Coho salmon, Oncorhynchus kisutch, fry were exposed for 40 days to stable, sublethal concentrations of toluene (0.4, 0.8, 1.6, 3.2, 5.8 μl/liter) and naphthalene (0.2, 0.4, 0.7, 1.4 mg/liter) in fresh water. All fry were fed equal daily rations of Oregon Moist Pellet Formula II. Dry weights, wet weights, and lengths of fry exposed to the two highest concentrations of each toxicant for 40 days were significantly less than controls (P < 0.01). Growth per day, determined from weights and lengths, decreased linearly with increased concentrations. Fry exposed to naphthalene had a slower growth rate than fry exposed to equivalent concentrations (percentage of the 96-hour median lethal concentration or LC50) of toluene. Concentrations 18% of the LC50 of naphthalene and 26% of the LC50 of toluene had no effect on dry weight, wet weight, or length of exposed fry.