Cloud droplet chemical composition is a key observable property that can aid understanding of how aerosols and clouds interact. As part of the Clouds, Aerosols and Monsoon Processes – Philippines ...Experiment (CAMP2Ex), three case studies were analyzed involving collocated airborne sampling of relevant clear and cloudy air masses associated with maritime warm convection. Two of the cases represented a polluted marine background, with signatures of transported East Asian regional pollution, aged over water for several days, while the third case comprised a major smoke transport event from Kalimantan fires.
Sea salt was a dominant component of cloud droplet composition, in spite of fine particulate enhancement from regional anthropogenic sources. Furthermore, the proportion of sea salt was enhanced relative to sulfate in rainwater and may indicate both a propensity for sea salt to aid warm rain production and an increased collection
efficiency of large sea salt particles by rain in subsaturated environments. Amongst cases, as precipitation became more significant, so too did the variability in the sea salt to (non-sea salt) sulfate ratio. Across cases, nitrate and ammonium were fractionally greater in cloud water than fine-mode aerosol particles; however, a strong
covariability in cloud water nitrate and sea salt was suggestive of prior uptake of nitrate on large salt particles.
A mass-based closure analysis of non-sea salt sulfate compared the cloud water air-equivalent mass concentration to the concentration of aerosol particles serving as cloud condensation nuclei for droplet activation. While sulfate found in cloud was generally constrained by the sub-cloud aerosol concentration, there was significant
intra-cloud variability that was attributed to entrainment – causing evaporation of sulfate-containing droplets –and losses due to precipitation. In addition, precipitation tended to promote mesoscale variability in the sub-cloud aerosol through a combination of removal, convective downdrafts, and dynamically driven convergence. Physical
mechanisms exerted such strong control over the cloud water compositional budget that it was not possible to isolate any signature of chemical production/loss using in-cloud observations. The cloud-free environment surrounding the non-precipitating smoke case indicated sulfate enhancement compared to convective mixing quantified by a stable gas tracer; however, this was not observed in the cloud water (either through use of ratios
or the mass closure), perhaps implying that the warm convective cloud timescale was too short for chemical production to be a leading-order budgetary term and because precursors had already been predominantly exhausted.
Closure of other species was truncated by incomplete characterization of coarse aerosol (e.g., it was found that only 10 %–50% of sea salt mass found in cloud was captured during clear-air sampling) and unmeasured gasphase abundances affecting closure of semi-volatile aerosol species (e.g., ammonium, nitrate and organic) and soluble volatile organic compound contributions to total organic carbon in cloud water.
Abstract
We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 ...motifs, finding that hRev1 exhibited stronger affinity for parallel-stranded G4 than either anti-parallel or hybrid folds. Amino acids in the αE helix of insert-2 were identified as being important for G4 binding. Mutating E466 and Y470 to alanine selectively perturbed G4 binding affinity. The E466K mutant restored wild-type G4 binding properties. Using a forward mutagenesis assay, we discovered that loss of hRev1 increased G4 mutation frequency >200-fold compared to the control sequence. Base substitutions and deletions occurred around and within the G4 motif. Pyridostatin (PDS) exacerbated this effect, as the mutation frequency increased >700-fold over control and deletions upstream of the G4 site more than doubled. Mutagenic replication of G4 DNA (±PDS) was partially rescued by wild-type and E466K hRev1. The E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency. These findings have implications for the role of insert-2, a motif conserved in vertebrates but not yeast or plants, in Rev1-mediated suppression of mutagenesis during G4 replication.
Hong Kong Chest Clinics.
To conduct a prospective study investigating the role of a whole-blood interferon-gamma release assay, QuantiFERON®-TB Gold In-Tube (QFT-GIT), in the diagnosis of ...smear-negative tuberculosis (TB). The QFT-GIT result was compared with the final confirmed diagnosis after 12 months.
Of 262 smear-negative subjects, 188 had active TB, 167 (88.8%) of whom were QFT-GIT-positive; 74 had inactive/non-TB, 30 (40.5%) of whom were QFT-GIT-negative. The positive (PPV) and negative predictive values for active TB were respectively 79.1% and 58.8%. For this target group with high TB prevalence (71.8%), a positive test increased the chance of active disease by only 7.3%. Despite a positive likelihood ratio (LR) of 1.49, the negative LR was 0.28, making the diagnosis of active TB much less likely after a negative test. Although sensitivity and specificity showed no difference across different age groups, the PPV decreased (P < 0.001) with increasing age, likely reflecting the increased prevalence of competing diagnoses.
In an area with a high prevalence of latent TB infection, a positive QFT-GIT test does not add much to confirm the diagnosis of smear-negative TB, while a negative test indicates a need for further investigation.
A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines ...from six 2.9 GW(th) nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the 10(-3) eV(2)<|Δm(41)(2) |< 0.3 eV(2) range. The relative spectral distortion due to the disappearance of electron antineutrinos was found to be consistent with that of the three-flavor oscillation model. The derived limits on sin(2) 2θ(14) cover the 10(-3) eV(2) ≲ |Δm(41)(2)| ≲ 0.1 eV(2) region, which was largely unexplored.
This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 ...m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse β decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18) cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43) cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.
Mr. Os (Hong Kong) is the first study to address the risk factors for osteoporosis in Asian men. A standardized, structured interview and dual X-ray densitometry (DEXA) were performed on 2,000 ...Chinese men aged 65-92. By multiple regression, the following factors were found to be positively associated with BMD at both the total hip and the spine: body weight, grip strength and a history of diabetes mellitus. The following factors were found to be negatively associated with BMD at both the total hip and spine: cigarette smoking, a history of gastrectomy or bowel resection, current use of inhaled steroid and a history of fracture after 50 years. Moreover, a history of chronic obstructive pulmonary disease (COPD) was negatively associated with BMD at the total hip, and age, the use of an alpha-blocker, thiazide diuretic and nitrate were associated with a higher BMD at the spine. A total of 21.8% of the variance in total hip and 31.5% of the variance in total spine BMD was accounted for in the multivariate analysis.
A regional chemical transport model assimilated with monthly mean satellite and ground based aerosol optical depth (AOD) observations was used to produce three dimensional distributions of aerosols ...throughout Asia for a period of four years. The model was evaluated with daily assimilation of AOD for the month of April 2005. Sulfur Transport dEposition Model (STEM), a regional chemical transport model, was used to simulate aerosol distributions at a resolution of 50
×
50
km with a time interval of 3
h. Monthly mean Moderate Resolution Imaging Spectroradiometer (MODIS) AOD along with AErosol RObotic NETwork (AERONET) AOD was used in an optimal interpolation assimilation scheme to yield regional distributions of aerosols. The MODIS AOD and aerosol fine mode fraction information (where available) were used in the assimilation technique. The daily assimilation of AOD results shows that the optimal interpolation algorithm is able to significantly improve model aerosol mass prediction skills at the two sites in Asia. Sensitivity studies were also conducted with different assimilation parameters on a daily assimilation scale and these results are discussed. The assimilation results of four-year aerosol fields were used to study the spatial and temporal distribution of aerosols in Asia. Two remote sites, Hanimaadhoo and Gosan were chosen as the case studies to study the outflow from the Indian subcontinent and East Asia. Seasonal and vertical structures of the aerosols are presented at these two sites. Positive Matrix Factorization (PMF), a factor analytic method was also used to characterize the source profile and source contribution at these two locations. A three-factor solution was able to explain more than 80% of the variation in the individual species at Hanimaadhoo and 90% variation of aerosol loadings at Gosan. The four-year averaged PMF model results were able to capture the seasonality of anthropogenic and dust loadings at both these locations. In addition, the PMF model identified the differences in the composition of anthropogenic aerosols over Hanimaadhoo and Gosan reflecting the differences in regional emissions. The PMF derived factors could be used as additional constraints for future assimilation studies.
Summary Telomere length (TL), as a reflection of aging and inflammatory processes, may be associated with bone mineral density (BMD). This study examines the association between TL and BMD ...cross-sectionally and the rate of bone loss over a 4-year period in 1,867 Chinese elderly community living subjects. After adjusting for confounding factors, no association was observed with BMD or bone loss. The decline in BMD with aging is not reflected by corresponding changes in telomere length. Introduction Bone mineral density (BMD) is influenced by the dynamics of aging, inflammatory, and bone remodeling processes. Telomere length (TL) is a reflection of the former two processes and may also be associated with bone loss. Methods Hip BMD was measured in 1,867 Chinese elderly community living subjects and the relationship between leukocyte TL measured using quantitative real-time polymerase chain reaction, and bone loss after 4 years was examined. Results Women had greater bone loss than men. In women, age of menopause, menarche, estrogen treatment/replacement therapy, and history of previous fracture were also among the significant covariates. However, in multivariate analyses, TL was not associated with BMD in either sex. Conclusions TL was not associated with either baseline BMD or bone loss over 4 years and accounted for less than 1.6% of the baseline BMD.
Thrombin-activatable fibrinolysis inhibitor (TAFI) is a circulating zymogen that is activated physiologically by the thrombin/thrombomodulin complex to activated TAFI (TAFIa) which is a basic ...carboxypeptidase. Substrates include fibrin, leading to a reduction in rate of plasmin generation, and several proinflammatory mediators such as bradykinin, thrombin-cleaved osteopontin and complement factor C5a. TAFI-deficient mice have no phenotype without being challenged and TAFIa appears to play a limited role in physiological fibrinolysis in vivo. In several disease models, the TAFI-deficient mice have different outcomes from the wild type (WT), but whether the difference is beneficial or an exacerbation of the disease depends on the model. The consequences of TAFI deficiency include increased plasmin as a result of enhanced incorporation of plasminogen and tissue plasminogen activator into the fibrin clot, but also loss of its ability to degrade other substrates, with the resultant up-regulation of several proinflammatory mediators, including C5a. Criteria are recommended to demonstrate that a substrate is a physiological substrate of TAFIa.
Summary Objective Investigate a role for calcitonin gene-related peptide (CGRP) in osteoarthritis (OA)-related pain. Design Neutralizing antibodies to CGRP were generated de novo . One of these ...antibodies, LY2951742, was characterized in vitro and tested in pre-clinical in vivo models of OA pain. Results LY2951742 exhibited high affinity to both human and rat CGRP (KD of 31 and 246 pM, respectively). The antibody neutralized CGRP-mediated induction of cAMP in SK-N-MC cells in vitro and capsaicin-induced dermal blood flow in the rat. Neutralization of CGRP significantly reduced pain behavior as measured by weight bearing differential in the rat monoiodoacetate model of OA pain in a dose-dependent manner. Moreover, pain reduction with neutralization of CGRP occurred independently of prostaglandins, since LY2951742 and NSAIDs worked additively in the NSAID-responsive version of the model and CGRP neutralization remained effective in the NSAID non-responsive version of the model. Neutralization of CGRP also provided dose-dependent and prolonged (>60 days) pain reduction in the rat meniscal tear model of OA after only a single injection of LY2951742. Conclusions LY2951742 is a high affinity, neutralizing antibody to CGRP. Neutralization of CGRP is efficacious in several OA pain models and works independently of NSAID mechanisms of action. LY2951742 holds promise for the treatment of pain in OA patients.
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