Baroclinic Vorticity Production in Protoplanetary Disks; Part I: Vortex Formation

The formation of vortices in protoplanetary disks is explored via pseudo-spectral numerical simulations of an anelastic-gas model. This model is a coupled set of equations for vorticity and temperature in two dimensions which includes baroclinic vorticity production and radiative cooling. Vortex formation is unambiguously shown to be caused by baroclinicity because (1) these simulations have zero initial perturbation vorticity and a nonzero initial temperature distribution; and (2) turning off the baroclinic term halts vortex formation, as shown by an immediate drop in kinetic energy and vorticity. Vortex strength increases with: larger background temperature gradients; warmer background temperatures; larger initial temperature perturbations; higher Reynolds number; and higher resolution. In the simulations presented here vortices form when the background temperatures are $\sim 200K$ and vary radially as $r^{-0.25}$, the initial vorticity perturbations are zero, the initial temperature perturbations are 5% of the background, and the Reynolds number is $10^9$. A sensitivity study consisting of 74 simulations showed that as resolution and Reynolds number increase, vortices can form with smaller initial temperature perturbations, lower background temperatures, and smaller background temperature gradients. For the parameter ranges of these simulations, the disk is shown to be convectively stable by the Solberg-H{\o}iland criteria.Comment: Originally submitted to The Astrophysical Journal April 3, 2006; resubmitted November 3, 2006; accepted Dec 5, 200

Ethanol-induced Modulation of Hepatocellular Extracellular Signal-regulated Kinase-1/2 Activity via 4-Hydroxynonenal

Modulation of the extracellular signal-regulated kinases (ERK-1/2), a signaling pathway directly associated with cell proliferation, survival, and homeostasis, has been implicated in several pathologies, including alcoholic liver disease. However, the underlying mechanism of ethanol-induced ERK-1/2 modulation remains unknown. This investigation explored the effects of ethanol-associated oxidative stress on constitutive hepatic ERK-1/2 activity and assessed the contribution of the lipid peroxidation product 4-hydroxynonenal (4-HNE) to the observations made in vivo. Constitutive ERK-1/2 phosphorylation was suppressed in hepatocytes isolated from rats chronically consuming ethanol for 45 days. This observation was associated with an increase in 4-HNE-ERK monomer adduct concentration and a hepatic cellular and lobular redistribution of ERK-1/2 that correlated with 4-HNE-protein adduct accumulation. Chronic ethanol consumption was also associated with a decrease in hepatocyte nuclear ELK-1 phosphorylation, independent of changes in total nuclear ELK-1 protein. Primary hepatocytes treated with concentrations of 4-HNE consistent with those occurring during oxidative stress displayed a concentration-dependent decrease in constitutive ERK-1/2 phosphorylation, activity, and nuclear localization that negatively correlated with 4-HNE-ERK-1/2 monomer adduct accumulation. These data paralleled the decreased phosphorylation of the downstream kinase ELK-1. Molar ratios of purified ERK-2 to 4-HNE consistent with pathologic ratios found in vivo resulted in protein monomer-adduct formation across a range of concentrations. Collectively, these data demonstrate a novel association between ethanol-induced lipid peroxidation and the inhibition of constitutive ERK-1/2, and suggest an inhibitory mechanism mediated by the lipid peroxidation product 4-hydroxynonenal

Comparison of tumour-based (Petersen Index) and inflammation-based (Glasgow Prognostic Score) scoring systems in patients undergoing curative resection for colon cancer

After resection, it is important to identify colon cancer patients, who are at a high risk of recurrence and who may benefit from adjuvant treatment. The Petersen Index (PI), a prognostic model based on pathological criteria is validated in Dukes' B and C disease. Similarly, the modified Glasgow Prognostic Score (mGPS) based on biochemical criteria has also been validated. This study compares both the scores in patients undergoing curative resection of colon cancer. A total of 244 patients underwent elective resection between 1997 and 2005. The PI was constructed from pathological reports; the mGPS was measured pre-operatively. The median follow-up was 67 months (minimum 36 months) during which 109 patients died; 68 of them from cancer. On multivariate analysis of age, Dukes' stage, PI and mGPS, age (hazard ratio, HR, 1.74, P=0.001), Dukes' stage (HR, 3.63, P<0.001), PI (HR, 2.05, P=0.010) and mGPS (HR, 2.34, P<0.001) were associated independently with cancer-specific survival. Three-year cancer-specific survival rates for Dukes' B patients with the low-risk PI were 98, 92 and 82% for the mGPS of 0, 1 and 2, respectively (P<0.05). The high-risk PI population is small, in particular for Dukes' B disease (9%). The mGPS further stratifies those patients classified as low risk by the PI. Combining both the scoring systems could identify patients who have undergone curative surgery but are at high-risk of cancer-related death, therefore guiding management and trial stratification

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Imaging Lipid Distributions in Model Monolayers by ToF-SIMS with Selectively Deuterated Components and Principal Components Analysis

Abstract Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) provides the capability to image the distribution of molecular ions and their associated fragments that are emitted from monolayer films. ToF-SIMS can be applied to the analysis of monolayers of complex lipid mixtures that act as a model to understand the organization of cell membranes into solid-like domains called lipid rafts. The ability to determine the molecular distribution of lipids using ToF-SIMS in monolayer films is also important in studies of the function of pulmonary surfactant. One of the limitations of the use of ToF-SIMS to studies of complex lipid mixtures found in biological systems, arises from the similarity of the mass fragments that are emitted from the components of the lipid mixture. The use of selectively deuterated components in a mixture overcomes this limitation and results in an unambiguous assignment of specific lipids to particular surface domains. The use of deuterium labeling to identify specific lipids in a multi-component mixture can be done by the deuteration of a single lipid or by the addition of more than one lipid with selectively deuterated components. The incorporation of deuterium into the lipid chains does not alter the miscibility or phase behavior of these systems. The use of deuterium labeling to identify lipids and determine their distribution in monolayer films will be demonstrated using two biological systems. Principal components analysis (PCA) is used to further analyze these deuterated systems checking for the origin of the various mass fragments present

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

Effects of spring temperature and volcanic eruptions on wader productivity

Key demographic parameters often show substantial annual variation that can have important consequences for rates of population growth. Since 2011 we have conducted annual estimates of the productivity of Icelandic Black-tailed Godwits Limosa limosa islandica over a large part of its breeding range. During this period, a volcanic eruption resulted in extensive dust deposition across the region

Global Precipitation Measurement Cold Season Precipitation Experiment (GCPEx): For Measurement Sake Let it Snow

As a component of the Earth's hydrologic cycle, and especially at higher latitudes,falling snow creates snow pack accumulation that in turn provides a large proportion of the fresh water resources required by many communities throughout the world. To assess the relationships between remotely sensed snow measurements with in situ measurements, a winter field project, termed the Global Precipitation Measurement (GPM) mission Cold Season Precipitation Experiment (GCPEx), was carried out in the winter of 2011-2012 in Ontario, Canada. Its goal was to provide information on the precipitation microphysics and processes associated with cold season precipitation to support GPM snowfall retrieval algorithms that make use of a dual-frequency precipitation radar and a passive microwave imager on board the GPM core satellite,and radiometers on constellation member satellites. Multi-parameter methods are required to be able to relate changes in the microphysical character of the snow to measureable parameters from which precipitation detection and estimation can be based. The data collection strategy was coordinated, stacked, high-altitude and in-situ cloud aircraft missions with three research aircraft sampling within a broader surface network of five ground sites taking in-situ and volumetric observations. During the field campaign 25 events were identified and classified according to their varied precipitation type, synoptic context, and precipitation amount. Herein, the GCPEx fieldcampaign is described and three illustrative cases detailed

A developmental analysis of communication between mothers and infants with Down's syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68850/2/10.1177_027112148300300110.pd

The association between subjective memory complaint and objective cognitive function in older people with previous major depression

The goal of this study is to investigate associations between subjective memory complaint and objective cognitive performance in older people with previous major depression-a high-risk sample for cognitive impairment and later dementia. A cross-sectional study was carried out in people aged 60 or over with previous major depression but not fulfilling current major depression criteria according to DSM-IV-TR. People with dementia or Mini-Mental State Examination score less than 17 were excluded. Subjective memory complaint was defined on the basis of a score ≧4 on the subscale of Geriatric Mental State schedule, a maximum score of 8. Older people aged equal or over 60 without any psychiatric diagnosis were enrolled as healthy controls. Cognitive function was evaluated using a series of cognitive tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility in all participants. One hundred and thirteen older people with previous major depression and forty-six healthy controls were enrolled. Subjective memory complaint was present in more than half of the participants with depression history (55.8%). Among those with major depression history, subjective memory complaint was associated with lower total immediate recall and delayed verbal recall scores after adjustment. The associations between subjective memory complaint and worse memory performance were stronger in participants with lower depressive symptoms (Hamilton Depression Rating Scale score<7). The results suggest subjective memory complaint may be a valid appraisal of memory performance in older people with previous major depression and consideration should be given to more proactive assessment and follow-up in these clinical samples