21,418 research outputs found
Covariant Bardeen Perturbation Formalism
In a previous work we obtained a set of necessary conditions for the linear
approximation in cosmology. Here we discuss the relations of this approach with
the so called covariant perturbations. It is often argued in the literature
that one of the main advantages of the covariant approach to describe
cosmological perturbations is that the Bardeen formalism is coordinate
dependent. In this paper we will reformulate the Bardeen approach in a
completely covariant manner. For that, we introduce the notion of pure and
mixed tensors, which yields an adequate language to treat both perturbative
approaches in a common framework. We then stress that in the referred covariant
approach one necessarily introduces an additional hyper-surface choice to the
problem. Using our mixed and pure tensors approach, we were able to construct a
one-to-one map relating the usual gauge dependence of the Bardeen formalism
with the hyper-surface dependence inherent to the covariant approach. Finally,
through the use of this map, we define full non-linear tensors that at first
order correspond to the three known gauge invariant variables ,
and , which are simultaneously foliation and gauge invariant. We then
stress that the use of the proposed mixed tensors allows one to construct
simultaneously gauge and hyper-surface invariant variables at any order.Comment: 15 pages, no figures, revtex4-1, accepted for publication in PRD,
typos fixed, improved discussion about higher order gauge and foliation
invarianc
Evolution of TFF-based perfusion: A path towards non product sieving and direct chromatography integration
Manufacturers of therapeutic proteins are becoming increasingly interested in continuous bioprocessing. Via uninterrupted medium exchange, perfusion cell culture yields higher volumetric productivity than traditional batch/fed-batch processes with 2 to 5 fold higher cell density and cultivation duration. In addition, an uninterrupted removal of therapeutic proteins promotes a desired alignment with integrated continuous purification processes to eliminate large hold tanks. Hollow fiber tangential flow filtration (TFF) is commonly used for cell retention in perfusion cell culture. In these perfusion systems the major limitation can be inefficient or decaying product sieving. This increases product’s retention time in the bioreactor, which may detrimentally affect the target protein quality attributes and decrease yield.
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The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues
Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation
within intron 1 of the FXN gene, leading to reduced expression of frataxin protein.
Evidence suggests that the mutation may induce epigenetic changes and heterochromatin
formation, thereby impeding gene transcription. In particular, studies using FRDA patient
blood and lymphoblastoid cell lines have detected increased DNA methylation of specific
CpG sites upstream of the GAA repeat and histone modifications in regions flanking the
GAA repeat. In this report we show that such epigenetic changes are also present in
FRDA patient brain, cerebellum and heart tissues, the primary affected systems of the
disorder. Bisulfite sequence analysis of the FXN flanking GAA regions reveals a shift in
the FRDA DNA methylation profile, with upstream CpG sites becoming consistently
hypermethylated and downstream CpG sites becoming consistently hypomethylated. We
also identify differential DNA methylation at three specific CpG sites within the FXN
promoter and one CpG site within exon 1. Furthermore, we show by chromatin
immunoprecipitation (ChIP) analysis that there is overall decreased histone H3K9
acetylation together with increased H3K9 methylation of FRDA brain tissue. Further
studies of brain, cerebellum and heart tissues from our GAA repeat expansion-containing
FRDA YAC transgenic mice reveal comparable epigenetic changes to those detected in
FRDA patient tissue. We have thus developed a mouse model that will be a valuable
resource for future therapeutic studies targeting epigenetic modifications of the FXN gene
to increase frataxin expression
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