The relative importance of competing pathways for the formation of high-molecular-weight peroxides in the ozonolysis of organic aerosol particles

High-molecular-weight (HMW) organic compounds are an important component of atmospheric particles, although their origins, possibly including in situ formation pathways, remain incompletely understood. This study investigates the formation of HMW organic peroxides through reactions involving stabilized Criegee intermediates (SCI's). The model system is methyl oleate (MO) mixed with dioctyl adipate (DOA) and myristic acid (MA) in submicron aerosol particles, and Criegee intermediates are formed by the ozonolysis of the double bond in methyl oleate. An aerosol flow tube coupled to a quadrupole aerosol mass spectrometer (AMS) is employed to determine the relative importance of different HMW organic peroxides following the ozonolysis of different mixing mole fractions of MO in DOA and MA. Possible peroxide products include secondary ozonides (SOZ's), α-acyloxyalkyl hydroperoxides and α-acyloxyalkyl alkyl peroxides (αAAHP-type compounds), diperoxides, and monoperoxide oligomers. Of these, the AMS data identify two SOZ's as major HMW products in the ozonolysis of pure methyl oleate as well as in an inert matrix of DOA to as low as 0.04 mole fraction MO. In comparison, in mixed particles of MO and MA, αAAHP-type compounds form in high yields for MO mole fractions of 0.5 or less, suggesting that SCI's efficiently attack the carboxylic acid group of myristic acid. The reactions of SCI's with carboxylic acid groups to form αAAHP-type compounds therefore compete with those of SCI's with aldehydes to form SOZ's, provided that both types of functionalities are present at significant concentrations. The results therefore suggest that SCI's in atmospheric particles contribute to the transformation of carboxylic acids and other protic groups into HMW organic peroxides

Attaching negative structures to model cut-outs in the vibration analysis of structures

The presence of a hole, cut-out or void in a structure makes it difficult to be modelled for calculating natural frequencies. A theoretical basis for simplifying the modelling of cut-outs in a structure by attaching a negative structure is presented. The Dynamic Stiffness Method has been used to prove that this method yields the required natural frequencies. The derivations also show the presence of additional natural frequencies which correspond to the vibration of the positive and negative parts vibrating together while the actual structure with the hole or cut-out usually remains stationary

Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc

published_or_final_versio

An essential function for the ATR-Activation-Domain (AAD) of TopBP1 in mouse development and cellular senescence

ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development

Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome

While next-generation sequencing has accelerated the discovery of human disease genes, progress has been largely limited to the "low hanging fruit" of mutations with obvious exonic coding or canonical splice site impact. In contrast, the lack of high-throughput, unbiased approaches for functional assessment of most noncoding variants has bottlenecked gene discovery. We report the integration of transcriptome sequencing (RNA-seq), which surveys all mRNAs to reveal functional impacts of variants at the transcription level, into the gene discovery framework for a unique human disease, microcephaly-micromelia syndrome (MMS). MMS is an autosomal recessive condition described thus far in only a single First Nations population and causes intrauterine growth restriction, severe microcephaly, craniofacial anomalies, skeletal dysplasia, and neonatal lethality. Linkage analysis of affected families, including a very large pedigree, identified a single locus on Chromosome 21 linked to the disease (LOD > 9). Comprehensive genome sequencing did not reveal any pathogenic coding or canonical splicing mutations within the linkage region but identified several nonconserved noncoding variants. RNA-seq analysis detected aberrant splicing in DONSON due to one of these noncoding variants, showing a causative role for DONSON disruption in MMS. We show that DONSON is expressed in progenitor cells of embryonic human brain and other proliferating tissues, is co-expressed with components of the DNA replication machinery, and that Donson is essential for early embryonic development in mice as well, suggesting an essential conserved role for DONSON in the cell cycle. Our results demonstrate the utility of integrating transcriptomics into the study of human genetic disease when DNA sequencing alone is not sufficient to reveal the underlying pathogenic mutation

On the link between ocean biota emissions, aerosol, and maritime clouds: Airborne, ground, and satellite measurements off the coast of California

Surface, airborne, and satellite measurements over the eastern Pacific Ocean off the coast of California during the period between 2005 and 2007 are used to explore the relationship between ocean chlorophyll a, aerosol, and marine clouds. Periods of enhanced chlorophyll a and wind speed are coincident with increases in particulate diethylamine and methanesulfonate concentrations. The measurements indicate that amines are a source of secondary organic aerosol in the marine atmosphere. Subsaturated aerosol hygroscopic growth measurements indicate that the organic component during periods of high chlorophyll a and wind speed exhibit considerable water uptake ability. Increased average cloud condensation nucleus (CCN) activity during periods of increased chlorophyll a levels likely results from both size distribution and aerosol composition changes. The available data over the period of measurements indicate that the cloud microphysical response, as represented by either cloud droplet number concentration or cloud droplet effective radius, is likely influenced by a combination of atmospheric dynamics and aerosol perturbations during periods of high chlorophyll a concentrations

Treatment of multiple liver metastasis from gastric carcinoma

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Regional variation of organic functional groups in aerosol particles on four U.S. east coast platforms during the International Consortium for Atmospheric Research on Transport and Transformation 2004 campaign

Submicron atmospheric aerosol samples were collected during the International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) 2004 campaign on four platforms: Chebogue Point (Nova Scotia, Canada), Appledore Island (Maine), the CIRPAS Twin Otter over Ohio, and the NOAA R/V Ronald H. Brown in the Gulf of Maine. Saturated aliphatic C-C-H, unsaturated aliphatic C=C−H, aromatic C=C−H, organosulfur C-O-S, carbonyl C=O, and organic hydroxyl C-OH functional groups were measured by calibrated Fourier Transform Infrared (FTIR) spectroscopy at all four sampling platforms. The ratio of molar concentrations of carbonyl C=O to saturated aliphatic C-C-H groups was nearly constant at each sampling platform, with the Twin Otter samples having the lowest ratio at 0.1 and the three more coastal platforms having ratios of 0.4 and 0.5. Organic mass (OM) to organic carbon (OC) ratios follow similar trends for the four platforms, with the Twin Otter having the lowest ratio of 1.4 and the coastal platforms having slightly higher values typically between 1.5 and 1.6. Organosulfur compounds were occasionally observed. Collocated organic aerosol sampling with two Aerodyne aerosol mass spectrometers for OM, a Sunset Laboratory thermo-optical analysis instrument for OC, and an ion chromatography-particle into liquid sampler (IC-PILS) for speciated carboxylic acids provided comparable results for most of the project, tracking the time series of FTIR OM, OC, and carbonyl groups, respectively, and showing simultaneous peaks of similar magnitude during most of the project. The FTIR/IC-PILS comparison suggests that about 9% of the carbonyl groups found in submicron organic particles on the Twin Otter are typically associated with low molecular weight carboxylic acids