122 research outputs found
On the Bergman representative coordinates
We study the set where the so-called Bergman representative coordinates (or
Bergman functions) form an immersion. We provide an estimate of the size of a
maximal geodesic ball with respect to the Bergman metric, contained in this
set. By concrete examples we show that these estimates are the best possible.Comment: 20 page
Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices
BackgroundEmissions from a large peat fire in North Carolina in 2008 were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments.MethodsSize-fractionated particulate matter (PM; ultrafine, fine, and coarse) were obtained from the peat fire while smoldering (ENCF-1) or when nearly extinguished (ENCF-4). Extracted samples were analyzed for chemical constituents and endotoxin content. Female CD-1 mice were exposed via oropharyngeal aspiration to 100ΞΌg/mouse, and assessed for relative changes in lung and systemic markers of injury and inflammation. At 24h post-exposure, hearts were removed for ex vivo functional assessments and ischemic challenge. Lastly, 8mm diameter lung slices from CD-1 mice were exposed (11ΞΌg)βΒ±βco-treatment of PM with polymyxin B (PMB), an endotoxin-binding compound.ResultsOn an equi-mass basis, coarse ENCF-1PM had the highest endotoxin content and elicited the greatest pro-inflammatory responses in the mice including: increases in bronchoalveolar lavage fluid protein, cytokines (IL-6, TNF-Ξ±, and MIP-2), neutrophils and intracellular reactive oxygen species (ROS) production. Exposure to fine or ultrafine particles from either period failed to elicit significant lung or systemic effects. In contrast, mice exposed to ENCF-1 ultrafine PM developed significantly decreased cardiac function and greater post-ischemia-associated myocardial infarction. Finally, similar exposures to mouse lung slices induced comparable patterns of cytokine production; and these responses were significantly attenuated by PMB.ConclusionsThe findings suggest that exposure to coarse PM collected during a peat fire causes greater lung inflammation in association with endotoxin and ROS, whereas the ultrafine PM preferentially affected cardiac responses. In addition, lung tissue slices were shown to be a predictive, alternative assay to assess pro-inflammatory effects of PM of differing size and composition. Importantly, these toxicological findings were consistent with the cardiopulmonary health effects noted in epidemiologic reports from exposed populations
Operator theory and function theory in Drury-Arveson space and its quotients
The Drury-Arveson space , also known as symmetric Fock space or the
-shift space, is a Hilbert function space that has a natural -tuple of
operators acting on it, which gives it the structure of a Hilbert module. This
survey aims to introduce the Drury-Arveson space, to give a panoramic view of
the main operator theoretic and function theoretic aspects of this space, and
to describe the universal role that it plays in multivariable operator theory
and in Pick interpolation theory.Comment: Final version (to appear in Handbook of Operator Theory); 42 page
A Survey on the Krein-von Neumann Extension, the corresponding Abstract Buckling Problem, and Weyl-Type Spectral Asymptotics for Perturbed Krein Laplacians in Nonsmooth Domains
In the first (and abstract) part of this survey we prove the unitary
equivalence of the inverse of the Krein--von Neumann extension (on the
orthogonal complement of its kernel) of a densely defined, closed, strictly
positive operator, for some in a Hilbert space to an abstract buckling problem operator.
This establishes the Krein extension as a natural object in elasticity theory
(in analogy to the Friedrichs extension, which found natural applications in
quantum mechanics, elasticity, etc.).
In the second, and principal part of this survey, we study spectral
properties for , the Krein--von Neumann extension of the
perturbed Laplacian (in short, the perturbed Krein Laplacian)
defined on , where is measurable, bounded and
nonnegative, in a bounded open set belonging to a
class of nonsmooth domains which contains all convex domains, along with all
domains of class , .Comment: 68 pages. arXiv admin note: extreme text overlap with arXiv:0907.144
Phonon dispersion in 1-layer cuprate HgBa2CuO4+d
We investigate the low energy acoustical and optical modes in
using inelastic x-ray scattering (IXS). The
experimental phonon dispersion and the dynamical structure factor are compared
with an atomic shell model, and the set of the atomic potentials obtained are
discussed. Our results are also compared with those obtained by Raman
spectroscopy and with density-of-state data measured by inelastic neutron
scattering
Mediator and cohesin connect gene expression and chromatin architecture
Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect two DNA segments. The cohesin-loading factor Nipbl is associated with mediatorβcohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell.National Institutes of Health (U.S.) (Fellowship)Canadian Institutes of Health Research (Research Fellowship)National Institutes of Health (U.S.) (Grant R01 HG002668
Mutator Suppression and Escape from Replication ErrorβInduced Extinction in Yeast
Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase Ξ΄ (Pol Ξ΄) proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10β3 inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex) rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol Ξ΄ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol Ξ΄ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer
Face scanning and spontaneous emotion preference in Cornelia de Lange syndrome and Rubinstein-Taybi syndrome
Background
Existing literature suggests differences in face scanning in individuals with different socio-behavioural characteristics. Cornelia de Lange syndrome (CdLS) and Rubinstein-Taybi syndrome (RTS) are two genetically defined neurodevelopmental disorders with unique profiles of social behaviour.
Methods
Here, we examine eye gaze to the eye and mouth regions of neutrally expressive faces, as well as the spontaneous visual preference for happy and disgusted facial expressions compared to neutral faces, in individuals with CdLS versus RTS.
Results
Results indicate that the amount of time spent looking at the eye and mouth regions of faces was similar in 15 individuals with CdLS and 17 individuals with RTS. Both participant groups also showed a similar pattern of spontaneous visual preference for emotions.
Conclusions
These results provide insight into two rare, genetically defined neurodevelopmental disorders that have been reported to exhibit contrasting socio-behavioural characteristics and suggest that differences in social behaviour may not be sufficient to predict attention to the eye region of faces. These results also suggest that differences in the social behaviours of these two groups may be cognitively mediated rather than subcortically mediated
The impact of oxygen on the transcriptome of recombinant S. cerevisiae and P. pastoris - a comparative analysis
Background: Saccharomyces cerevisiae and Pichia pastoris are two of the most relevant microbial eukaryotic platforms for the production of recombinant proteins. Their known genome sequences enabled several transcriptomic profiling studies under many different environmental conditions, thus mimicking not only perturbations and adaptations which occur in their natural surroundings, but also in industrial processes. Notably, the majority of such transcriptome analyses were performed using non-engineered strains. In this comparative study, the gene expression profiles of S. cerevisiae and P. pastoris, a Crabtree positive and Crabtree negative yeast, respectively, were analyzed for three different oxygenation conditions (normoxic, oxygen-limited and hypoxic) under recombinant protein producing conditions in chemostat cultivations. Results: The major differences in the transcriptomes of S. cerevisiae and P. pastoris were observed between hypoxic and normoxic conditions, where the availability of oxygen strongly affected ergosterol biosynthesis, central carbon metabolism and stress responses, particularly the unfolded protein response. Steady state conditions under low oxygen set-points seemed to perturb the transcriptome of S. cerevisiae to a much lesser extent than the one of P. pastoris, reflecting the major tolerance of the baker's yeast towards oxygen limitation, and a higher fermentative capacity. Further important differences were related to Fab production, which was not significantly affected by oxygen availability in S. cerevisiae, while a clear productivity increase had been previously reported for hypoxically grown P. pastoris. Conclusions: The effect of three different levels of oxygen availability on the physiology of P. pastoris and S. cerevisiae revealed a very distinct remodelling of the transcriptional program, leading to novel insights into the different adaptive responses of Crabtree negative and positive yeasts to oxygen availability. Moreover, the application of such comparative genomic studies to recombinant hosts grown in different environments might lead to the identification of key factors for efficient protein production
Multiple Organ System Defects and Transcriptional Dysregulation in the Nipbl+/β Mouse, a Model of Cornelia de Lange Syndrome
Cornelia de Lange Syndrome (CdLS) is a multi-organ system birth defects disorder linked, in at least half of cases, to heterozygous mutations in the NIPBL gene. In animals and fungi, orthologs of NIPBL regulate cohesin, a complex of proteins that is essential for chromosome cohesion and is also implicated in DNA repair and transcriptional regulation. Mice heterozygous for a gene-trap mutation in Nipbl were produced and exhibited defects characteristic of CdLS, including small size, craniofacial anomalies, microbrachycephaly, heart defects, hearing abnormalities, delayed bone maturation, reduced body fat, behavioral disturbances, and high mortality (75β80%) during the first weeks of life. These phenotypes arose despite a decrease in Nipbl transcript levels of only βΌ30%, implying extreme sensitivity of development to small changes in Nipbl activity. Gene expression profiling demonstrated that Nipbl deficiency leads to modest but significant transcriptional dysregulation of many genes. Expression changes at the protocadherin beta (Pcdhb) locus, as well as at other loci, support the view that NIPBL influences long-range chromosomal regulatory interactions. In addition, evidence is presented that reduced expression of genes involved in adipogenic differentiation may underlie the low amounts of body fat observed both in Nipbl+/β mice and in individuals with CdLS
- β¦