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This is a copy of the slides presented at the meeting but not formally
written up for the volume.
Proteomics based clinical diagnostics systems utilize the principle of
protein identification as a means of biomarker profiling for disease
diagnosis. The current standardized immunoassay techniques such as Enzyme
linked Immunosorbent Assays (ELISA) are based on the fluorescent
detection of the antibody (Ab)-antigen (Ag) binding event. These
techniques are expensive; time consuming requiring a large sample volume.
We present here two electrical immunoassay techniques that can
potentially used for the rapid, multiplexed diagnosis of proteins for
disease identification. The first technique involves the use of
nanoporous templates in conjunction with microfabricated platforms with
metallic base electrodes resulting In the formation of a “nanowell” assay
system that is analogous to the micro titer well plate system. The
detection of the formation of binding complex is achieved by capacitive
measurement techniques. The dynamic range and the calibration of the
device has been performed with respective to the current gold standard in
proteomics. The second technique involves the use of microscale carriers
to transport ab’s to sensing sites on microfabricated base platforms. The
binding of the Ag’s to the Ab’s coupled to the carriers’ results in
measurable voltage changes that are recorded in a real time manner. The
calibration and the dynamic range of this device has also been
determined. Both these techniques demonstrate potential as early
diagnostic devices and their performance in detection of clinically
relevant proteins is demonstrated.
The regeneration niche defines the specific environmental requirements of the early phases of a plant's life cycle. It is critical for the long-term persistence of plant populations, particularly for obligate seeders that are highly vulnerable to stochastic events in fire-prone ecosystems. Here, we assessed germination characteristics and the relationship between population structure, soil seed bank density and fire response in Stachystemon vinosus (Euphorbiaceae), a rare endemic shrub from Western Australia, from burnt and long unburnt habitats. Many plants in long unburnt habitat were similar in size to those in recently burnt habitat. Soil seed bank density was related to plant abundance and fire history with density lower in burnt than unburnt sites. Thus, inter-fire recruitment may play a critical role in the requirements of the study species. To assess the dormancy status and germination requirements we used a ‘move-along’ experiment with temperatures from six seasonal phases of the year. Seeds were incubated under light and dark conditions, with and without smoked water, and with and without dry after-ripening. Germination was most effective when seeds were treated with smoked water and incubated in the dark at temperatures resembling autumn/winter conditions. After-ripening increased germination in light and dark incubated seeds in the absence of smoked water but was unnecessary for optimal germination in smoked water treated seeds. Irrespective of treatment, seeds showed a requirement for cooler temperatures for germination. These results suggest that rising temperatures and changes in fire regime associated with global warming may alter future germination responses of Stachystemon vinosus.
Consumption of certain berries appears to slow postprandial glucose absorption, attributable to polyphenols, which may benefit exercise and cognition, reduce appetite and/or oxidative stress. This randomised, crossover, placebo-controlled study determined whether polyphenol-rich fruits added to carbohydrate-based foods produce a dose-dependent moderation of postprandial glycaemic, glucoregulatory hormone, appetite and ex vivo oxidative stress responses. Twenty participants (eighteen males/two females; 24 (sd 5) years; BMI: 27 (sd 3) kg/m2) consumed one of five cereal bars (approximately 88 % carbohydrate) containing no fruit ingredients (reference), freeze-dried black raspberries (10 or 20 % total weight; LOW-Rasp and HIGH-Rasp, respectively) and cranberry extract (0·5 or 1 % total weight; LOW-Cran and HIGH-Cran), on trials separated by ≥5 d. Postprandial peak/nadir from baseline (Δmax) and incremental postprandial AUC over 60 and 180 min for glucose and other biochemistries were measured to examine the dose-dependent effects. Glucose AUC0–180 min trended towards being higher (43 %) after HIGH-Rasp v. LOW-Rasp (P=0·06), with no glucose differences between the raspberry and reference bars. Relative to reference, HIGH-Rasp resulted in a 17 % lower Δmax insulin, 3 % lower C-peptide (AUC0–60 min and 3 % lower glucose-dependent insulinotropic polypeptide (AUC0–180 min) P<0·05. No treatment effects were observed for the cranberry bars regarding glucose and glucoregulatory hormones, nor were there any treatment effects for either berry type regarding ex vivo oxidation, appetite-mediating hormones or appetite. Fortification with freeze-dried black raspberries (approximately 25 g, containing 1·2 g of polyphenols) seems to slightly improve the glucoregulatory hormone and glycaemic responses to a high-carbohydrate food item in young adults but did not affect appetite or oxidative stress responses at doses or with methods studied herein.
Several grass and broadleaf weed species around the world have evolved multiple-herbicide resistance at alarmingly increasing rates. Research on the biochemical and molecular resistance mechanisms of multiple-resistant weed populations indicate a prevalence of herbicide metabolism catalyzed by enzyme systems such as cytochrome P450 monooxygenases and glutathione S-transferases and, to a lesser extent, by glucosyl transferases. A symposium was conducted to gain an understanding of the current state of research on metabolic resistance mechanisms in weed species that pose major management problems around the world. These topics, as well as future directions of investigations that were identified in the symposium, are summarized herein. In addition, the latest information on selected topics such as the role of safeners in inducing crop tolerance to herbicides, selectivity to clomazone, glyphosate metabolism in crops and weeds, and bioactivation of natural molecules is reviewed.
Whole grain intake is associated with lower CVD risk in epidemiological studies. It is unclear to what extent cereal fibre, located primarily within the bran, is responsible. This review aimed to evaluate association between intake of whole grain, cereal fibre and bran and CVD risk. Academic databases were searched for human studies published before March 2018. Observational studies reporting whole grain and cereal fibre or bran intake in association with any CVD-related outcome were included. Studies were separated into those defining whole grain using a recognised definition (containing the bran, germ and endosperm in their natural proportions) (three studies, seven publications) and those using an alternative definition, such as including added bran as a whole grain source (eight additional studies, thirteen publications). Intake of whole grain, cereal fibre and bran were similarly associated with lower risk of CVD-related outcomes. Within the initial analysis, where studies used the recognised whole grain definition, results were less likely to show attenuation after adjustment for cereal fibre content. The fibre component of grain foods appears to play an important role in protective effects of whole grains. Adjusting for fibre content, associations remained, suggesting that additional components within the whole grain, and the bran component, may contribute to cardio-protective association. The limited studies and considerable discrepancy in defining and calculating whole grain intake limit conclusions. Future research should utilise a consistent definition and methodical approach of calculating whole grain intake to contribute to a greater body of consistent evidence surrounding whole grains.
In §1, we define a differential-integral operator, which for positive real indices is commonly known as the Liouville-Riemann generalized integral. For positive integer indices, we obtain an iterated integral. For negative real indices we obtain the Riemann-Holmgren (5; 9) generalized derivative, which for negative integer indices gives the ordinary derivative of order corresponding to the negative of such an integer. Following M. Riesz (10) we extend these ideas to include complex indices.
Utilising routine surveillance data, this study presents a method for generating a baseline comparison that can be used in future foodborne outbreak investigations following a case–case methodology. Salmonella and Campylobacter cases (2012–2015) from Maricopa County, AZ were compared to determine differences in risk factors, symptoms and demographics. For foods and other risk factors, adjusted odds ratios were developed using Campylobacter as the reference. Comparisons were also made for three major Salmonella subtypes, Typhimurium, Enteritidis and Poona as compared with Campylobacter. Salmonella cases were younger, while Campylobacter cases were more Hispanic and female. Campylobacter cases reported consuming peppers, sprouts, poultry, queso fresco, eggs and raw nuts more and reported contact with animal products, birds, visiting a farm or dairy, owning a pet, a sick pet, swimming in a river, lake or pond, or handling multiple raw meats more. Salmonella cases reported visiting a petting zoo and contact with a reptile more. There were significant variations by Salmonella subtype in both foods and exposures. We recommend departments conduct this analysis to generate a baseline comparison and a running average of relevant odds ratios allowing staff to focus on trace-back of contaminated food items earlier in the outbreak investigation process.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
Fe is an essential nutrient for many bacteria, and Fe supplementation has been reported to affect the composition of the gut microbiota in both Fe-deficient and Fe-replete individuals outside pregnancy. This study examined whether the dose of Fe in pregnancy multivitamin supplements affects the overall composition of the gut microbiota in overweight and obese pregnant women in early pregnancy. Women participating in the SPRING study with a faecal sample obtained at 16 weeks’ gestation were included in this substudy. For each subject, the brand of multivitamin used was recorded. Faecal microbiome composition was assessed by 16S rRNA sequencing and analysed with the QIIME software suite. Dietary intake of Fe was assessed using a FFQ at 16 weeks’ gestation. Women were grouped as receiving low (<60 mg/d, n 94) or high (≥60 mg/d; n 65) Fe supplementation. The median supplementary Fe intake in the low group was 10 (interquartile range (IQR) 5–10) v. 60 (IQR 60–60) mg/d in the high group (P<0·001). Dietary Fe intake did not differ between the groups (10·0 (IQR 7·4–13·3) v. 9·8 (IQR 8·2–13·2) mg/d). Fe supplementation did not significantly affect the composition of the faecal microbiome at any taxonomic level. Network analysis showed that the gut microbiota in the low Fe supplementation group had a higher predominance of SCFA producers. Pregnancy multivitamin Fe content has a minor effect on the overall composition of the gut microbiota of overweight and obese pregnant women at 16 weeks’ gestation.
Solvency II is currently one of the most sophisticated insurance regulatory regimes in the world. It is built around the principles of market consistency and embedding strong risk management and governance within insurance companies. For business with long-term guarantees, the original basis produced outcomes that were unacceptable to the member states. The original design was amended through Omnibus II. The working party has looked back at the outcome of the final regulation and comments on how well Solvency II has fared, principally from a UK perspective, relative to its initial goals of improved consumer protection, harmonisation, effective risk management and financial stability. We review Pillar 1’s market consistent valuation (including the risk margin and transitional measures) as well as the capital requirements (including internal models). We look at the impact this has on asset and liability management, pro-cyclicality and product design. We look at Pillars 2 and 3 in respect of the Own Risk and Solvency Assessment, liquidity and disclosure. Finally, we stand back and look at harmonisation and the implications of Brexit. In summary we conclude that Solvency II represents a huge improvement over Solvency I although it has not fully achieved the goals it aspired to. There are acknowledged shortfalls and imperfections where adjustments to Solvency II are likely. There remain other concerns around pro-cyclicality, and the appropriateness of market consistency is still open to criticism. It is hoped that the paper and the discussion that goes with it provide an insight into where Solvency II has taken European Insurance regulation and the directions in which it could evolve.
Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, anogenital distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette distance (AGD-AF) and anoclitoral distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls’ AGD. In total, 300 mother–daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: β=1.21, P=0.05; AGD-AC: β=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: β=1.65, P=0.02; AGD-AC: β=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.
We agree with Lake and colleagues on their list of “key ingredients” for building human-like intelligence, including the idea that model-based reasoning is essential. However, we favor an approach that centers on one additional ingredient: autonomy. In particular, we aim toward agents that can both build and exploit their own internal models, with minimal human hand engineering. We believe an approach centered on autonomous learning has the greatest chance of success as we scale toward real-world complexity, tackling domains for which ready-made formal models are not available. Here, we survey several important examples of the progress that has been made toward building autonomous agents with human-like abilities, and highlight some outstanding challenges.
McMurdo Dry Valleys (MDV; Ross Sea region, Antarctica) precipitation exhibits extreme seasonality in ion concentration, 3–5 orders of magnitude between summer and winter precipitation. To identify aerosol sources and investigate causes for the observed amplitude in concentration variability, four snow pits were sampled along a coast–Polar Plateau transect across the MDV. The elevation of the sites ranges from 50 to 2400 m and the distance from the coast from 8 to 93 km. Average chemistry gradients along the transect indicate that most species have either a predominant marine or terrestrial source in the MDV. Empirical orthogonal function analysis on the snow-chemistry time series shows that at least 57% of aerosol deposition occurs concurrently. A conceptual climate model, based on meteorological observations, is used to explain the strong seasonality in the MDV. Our results suggest that radiative forcing of the ice-free valleys creates a surface low-pressure cell during summer which promotes air-mass flow from the Ross Sea. The associated precipitating air mass is relatively warm, humid and contains a high concentration of aerosols. During winter, the MDV are dominated by air masses draining off the East Antarctic ice sheet, that are characterized by cold, dry and low concentrations of aerosols. The strong differences between these two air-mass sources create in the MDV a polar version of the monsoonal flow, with humid, warm summers and dry, cold winters.
Ice-core chemistry data from Victoria Lower Glacier, Antarctica, suggest, at least for the last 50 years, a direct influence of solar activity variations on the McMurdo Dry Valleys (MDV) climate system via controls on air-mass input from two competing environments: the East Antarctic ice sheet and the Ross Sea. During periods of increased solar activity, when total solar irradiance is relatively high, the MDV climate system appears to be dominated by air masses originating from the Ross Sea, leading to higher aerosol deposition. During reduced solar activity, the Antarctic interior seems to be the dominant air-mass source, leading to lower aerosol concentration in the ice-core record. We propose that the sensitivity of the MDV to variations in solar irradiance is caused by strong albedo differences between the ice-free MDV and the ice sheet.
An updated compilation of published and new data of major-ion (Ca, Cl, K, Mg, Na, NO3, SO4) and methylsulfonate (MS) concentrations in snow from 520 Antarctic sites is provided by the national ITASE (International Trans-Antarctic Scientific Expedition) programmes of Australia, Brazil, China, Germany, Italy, Japan, Korea, New Zealand, Norway, the United Kingdom, the United States and the national Antarctic programme of Finland. The comparison shows that snow chemistry concentrations vary by up to four orders of magnitude across Antarctica and exhibit distinct geographical patterns. The Antarctic-wide comparison of glaciochemical records provides a unique opportunity to improve our understanding of the fundamental factors that ultimately control the chemistry of snow or ice samples. This paper aims to initiate data compilation and administration in order to provide a framework for facilitation of Antarctic-wide snow chemistry discussions across all ITASE nations and other contributing groups. The data are made available through the ITASE web page (http://www2.umaine.edu/itase/content/syngroups/snowchem.html) and will be updated with new data as they are provided. In addition, recommendations for future research efforts are summarized.
A noticeable trait of iceberg ice is the presence of several sets of planar features cross-cutting each other at various angles. Close-up views of these features show that they consist of an array of individual air inclusions that differ in size, shape and spatial distribution. In none of the cases resolvable at the scale of our observations were these inclusions physically linked to form a continuous fracture plane, although they may have originated as such. All postdate the formation of ice veins.
OBJECTIVES/SPECIFIC AIMS: Accumulation of cholesterol-laden macrophages in arterial walls leads to atherosclerosis. LXRs induce expression of genes that are atheroprotective in macrophages including CCR7, a chemokine receptor that promotes their emigration from the plaque. CCR7 expression has been shown to be negatively regulated by phosphorylation of LXRα at S198 and is reduced in diabetic mice that show impaired plaque regression. I hypothesized that LXRα phosphorylation at S198 diminishes macrophage emigration from atherosclerotic plaque and contributes to impaired regression in diabetes. METHODS/STUDY POPULATION: Inducible LXRα S198A phosphorylation deficient knock in mouse were used as donors for bone marrow transplantation into mice prone to develop atherosclerosis. Plaques were developed by placing mice on western diet; and regression was induced by lowering their lipid levels. Aortic plaques were then analyzed by using morphometric, histological, and molecular analyses in control and diabetic mice expressing either LXRα WT or LXRα S198A during regression. RESULTS/ANTICIPATED RESULTS: Surprisingly, lack of phosphorylation increased plaque macrophage content and impaired regression under normoglycemic condition; however, it did not exacerbate diabetic regression. Plaques in diabetic mice were associated with increased LXRα S198 phosphorylation. Consistent with this, LXRα phosphorylation is enhanced in macrophages cultured under hyperglycemic conditions indicating glucose-dependent regulation of LXRα phosphorylation. Monocyte trafficking studies reveal that lack of phosphorylation and diabetes independently increase recruitment of monocytes in the plaque that might contribute to increased macrophage content. Importantly, I found that diabetes also increases macrophage retention in the plaque, which is reversed in the absence of phosphorylation. We predict that this increased retention results from inhibition of emigration of plaque macrophages through enhanced phosphorylation in diabetes. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that inhibiting LXRα phosphorylation could be beneficial in diabetic atherosclerosis to reverse the accumulation of macrophages in the plaque. This study imparts insight on regulation of plaque macrophage trafficking through LXRα S198 phosphorylation.