Fast Ensemble Smoothing

Smoothing is essential to many oceanographic, meteorological and hydrological applications. The interval smoothing problem updates all desired states within a time interval using all available observations. The fixed-lag smoothing problem updates only a fixed number of states prior to the observation at current time. The fixed-lag smoothing problem is, in general, thought to be computationally faster than a fixed-interval smoother, and can be an appropriate approximation for long interval-smoothing problems. In this paper, we use an ensemble-based approach to fixed-interval and fixed-lag smoothing, and synthesize two algorithms. The first algorithm produces a linear time solution to the interval smoothing problem with a fixed factor, and the second one produces a fixed-lag solution that is independent of the lag length. Identical-twin experiments conducted with the Lorenz-95 model show that for lag lengths approximately equal to the error doubling time, or for long intervals the proposed methods can provide significant computational savings. These results suggest that ensemble methods yield both fixed-interval and fixed-lag smoothing solutions that cost little additional effort over filtering and model propagation, in the sense that in practical ensemble application the additional increment is a small fraction of either filtering or model propagation costs. We also show that fixed-interval smoothing can perform as fast as fixed-lag smoothing and may be advantageous when memory is not an issue

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

ortho and para chromophores of green fluorescent protein: controlling electron emission and internal conversion

Green fluorescent protein (GFP) continues to play an important role in the biological and biochemical sciences as an efficient fluorescent probe and is also known to undergo light-induced redox transformations. Here, we employ photoelectron spectroscopy and quantum chemistry calculations to investigate how the phenoxide moiety controls the competition between electron emission and internal conversion in the isolated GFP chromophore anion, following photoexcitation with ultraviolet light in the range 400–230 nm. We find that moving the phenoxide group from the para position to the ortho position enhances internal conversion back to the ground electronic state but that adding an additional OH group to the para chromophore, at the ortho position, impedes internal conversion. Guided by quantum chemistry calculations, we interpret these observations in terms of torsions around the C–C–C bridge being enhanced by electrostatic repulsions or impeded by the formation of a hydrogen-bonded seven-membered ring. We also find that moving the phenoxide group from the para position to the ortho position reduces the energy required for detachment processes, whereas adding an additional OH group to the para chromophore at the ortho position increases the energy required for detachment processes. These results have potential applications in tuning light-induced redox processes of this biologically and technologically important fluorescent protein

Can standardized patients replace physicians as OSCE examiners?

BACKGROUND: To reduce inter-rater variability in evaluations and the demand on physician time, standardized patients (SP) are being used as examiners in OSCEs. There is concern that SP have insufficient training to provide valid evaluation of student competence and/or provide feedback on clinical skills. It is also unknown if SP ratings predict student competence in other areas. The objectives of this study were: to examine student attitudes towards SP examiners; to compare SP and physician evaluations of competence; and to compare predictive validity of these scores, using performance on the multiple choice questions examination (MCQE) as the outcome variable. METHODS: This was a cross-sectional study of third-year medical students undergoing an OSCE during the Internal Medicine clerkship rotation. Fifty-two students rotated through 8 stations (6 physician, 2 SP examiners). Statistical tests used were Pearson's correlation coefficient, two-sample t-test, effect size calculation, and multiple linear regression. RESULTS: Most students reported that SP stations were less stressful, that SP were as good as physicians in giving feedback, and that SP were sufficiently trained to judge clinical skills. SP scored students higher than physicians (mean 90.4% +/- 8.9 vs. 82.2% +/- 3.7, d = 1.5, p < 0.001) and there was a weak correlation between the SP and physician scores (coefficient 0.4, p = 0.003). Physician scores were predictive of summative MCQE scores (regression coefficient = 0.88 [0.15, 1.61], P = 0.019) but there was no relationship between SP scores and summative MCQE scores (regression coefficient = -0.23, P = 0.133). CONCLUSION: These results suggest that SP examiners are acceptable to medical students, SP rate students higher than physicians and, unlike physician scores, SP scores are not related to other measures of competence

Experimental investigation of GafChromic® EBT3 intrinsic energy dependence with kilovoltage x rays, 137Cs, and 60Co

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141567/1/mp12682_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141567/2/mp12682.pd

Insulin resistance in lean and overweight non-diabetic Caucasian adults: Study of its relationship with liver triglyceride content, waist circumference and BMI

Insulin resistance is the pathophysiological precursor of type 2 diabetes mellitus (DM-2), and its relationship with non-alcoholic fatty liver disease (NAFLD) has been widely studied in patients with obesity or metabolic syndrome using not only ultrasound but also liver biopsies or proton magnetic resonance spectroscopy (H1-MRS) to assess liver fat content. In contrast, there are no studies on insulin resistance and NAFLD in lean or overweight Caucasian individuals using H1-MRS or liver biopsies for the quantification of hepatic triglyceride content. Our objectives were to study the presence of insulin resistance in lean and overweight Caucasian adults and investigate its possible relationship with liver triglyceride content, waist circumference (as proxy of visceral adiposity), BMI, and cardiometabolic risk factors.A cross-sectional study was conducted in 113 non-obese, non-diabetic individuals classified as overweight (BMI 25–29.9 kg/m2) or lean (BMI 19.5–24.9 kg/m2). Hepatic triglyceride content was quantified by 3T H1-MRS. NAFLD was defined as hepatic triglyceride content >5.56%. Insulin resistance (HOMA-IR), serum adiponectin, and tumor necrosis factor (TNF) were determined.HOMA-IR was significantly correlated with hepatic triglyceride content (r:0.76; p<0.0001). The lean-with-NAFLD group had significantly higher HOMA-IR (p<0.001) and lower serum adiponectin (p<0.05) than the overweight-without-NAFLD group. Insulin resistance was independently associated with NAFLD but not with waist circumference or BMI. Regression analysis showed hepatic triglyceride content to be the most important determinant of insulin resistance (p<0.01).Our findings suggest that NAFLD, once established, seems to be involved in insulin resistance and cardio-metabolic risk factors above and beyond waist circumference and BMI in non-obese, non-diabetic Caucasian individuals

Conformational changes in α7 acetylcholine receptors underlying allosteric modulation by divalent cations

Allosteric modulation of membrane receptors is a widespread mechanism by which endogenous and exogenous agents regulate receptor function. For example, several members of the nicotinic receptor family are modulated by physiological concentrations of extracellular calcium ions. In this paper, we examined conformational changes underlying this modulation and compare these with changes evoked by ACh. Two sets of residues in the α7 acetylcholine receptor extracellular domain were mutated to cysteine and analyzed by measuring the rates of modification by the thiol-specific reagent 2-aminoethylmethane thiosulfonate. Using Ba2+ as a surrogate for Ca2+, we found a divalent-dependent decrease the modification rates of cysteine substitutions at M37 and M40, residues at which rates were also slowed by ACh. In contrast, Ba2+ had no significant effect at N52C, a residue where ACh increased the rate of modification. Thus divalent modulators cause some but not all of the conformational effects elicited by agonist. Cysteine substitution of either of two glutamates (E44 or E172), thought to participate in the divalent cation binding site, caused a loss of allosteric modulation, yet Ba2+ still had a significant effect on modification rates of these residues. In addition, the effect of Ba2+ at these residues did not appear to be due to direct occlusion. Our data demonstrate that modulation by divalent cations involves substantial conformational changes in the receptor extracellular domain. Our evidence also suggests the modulation occurs via a binding site distinct from one which includes either (or both) of the conserved glutamates at E44 or E172