Hollow Fiber Bioreactors for In Vivo-like Mammalian Tissue Culture

Tissue culture has been used for over 100 years to study cells and responses ex vivo. The convention of this technique is the growth of anchorage dependent cells on the 2-dimensional surface of tissue culture plastic. More recently, there is a growing body of data demonstrating more in vivo-like behaviors of cells grown in 3-dimensional culture systems. This manuscript describes in detail the set-up and operation of a hollow fiber bioreactor system for the in vivo-like culture of mammalian cells. The hollow fiber bioreactor system delivers media to the cells in a manner akin to the delivery of blood through the capillary networks in vivo. The system is designed to fit onto the shelf of a standard CO2 incubator and is simple enough to be set-up by any competent cell biologist with a good understanding of aseptic technique. The systems utility is demonstrated by culturing the hepatocarcinoma cell line HepG2/C3A for 7 days. Further to this and in line with other published reports on the functionality of cells grown in 3-dimensional culture systems the cells are shown to possess increased albumin production (an important hepatic function) when compared to standard 2-dimensional tissue culture

Age-related changes to the neural correlates of working memory which emerge after midlife

Previous research has indicated that the neural processes which underlie working memory change with age. Both age-related increases and decreases to cortical activity have been reported. This study investigated which stages of working memory are most vulnerable to age-related changes after midlife. To do this we examined age-differences in the 13 Hz steady state visually evoked potential (SSVEP) associated with a spatial working memory delayed response task. Participants were 130 healthy adults separated into a midlife (40-60 years) and an older group (61-82 years). Relative to the midlife group, older adults demonstrated greater bilateral frontal activity during encoding and this pattern of activity was related to better working memory performance. In contrast, evidence of age-related under activation was identified over left frontal regions during retrieval. Findings from this study suggest that after midlife, under-activation of frontal regions during retrieval contributes to age-related decline in working memory performance. © 2014 Macpherson, White, Ellis, Stough, Camfield, Silberstein and Pipingas

Hollow Fiber Bioreactors for In Vivo-like Mammalian Tissue Culture

Tissue culture has been used for over 100 years to study cells and responses ex vivo. The convention of this technique is the growth of anchorage dependent cells on the 2-dimensional surface of tissue culture plastic. More recently, there is a growing body of data demonstrating more in vivo-like behaviors of cells grown in 3-dimensional culture systems. This manuscript describes in detail the set-up and operation of a hollow fiber bioreactor system for the in vivo-like culture of mammalian cells. The hollow fiber bioreactor system delivers media to the cells in a manner akin to the delivery of blood through the capillary networks in vivo. The system is designed to fit onto the shelf of a standard CO2 incubator and is simple enough to be set-up by any competent cell biologist with a good understanding of aseptic technique. The systems utility is demonstrated by culturing the hepatocarcinoma cell line HepG2/C3A for 7 days. Further to this and in line with other published reports on the functionality of cells grown in 3-dimensional culture systems the cells are shown to possess increased albumin production (an important hepatic function) when compared to standard 2-dimensional tissue culture

Using the local density approximation and the LYP, BLYP, and B3LYP functionals within Reference--State One--Particle Density--Matrix Theory

For closed-shell systems, the local density approximation (LDA) and the LYP, BLYP, and B3LYP functionals are shown to be compatible with reference-state one-particle density-matrix theory, where this recently introduced formalism is based on Brueckner-orbital theory and an energy functional that includes exact exchange and a non-universal correlation-energy functional. The method is demonstrated to reduce to a density functional theory when the exchange-correlation energy-functional has a simplified form, i.e., its integrand contains only the coordinates of two electron, say r1 and r2, and it has a Dirac delta function -- delta(r1 - r2) -- as a factor. Since Brueckner and Hartree--Fock orbitals are often very similar, any local exchange functional that works well with Hartree--Fock theory is a reasonable approximation with reference-state one-particle density-matrix theory. The LDA approximation is also a reasonable approximation. However, the Colle--Salvetti correlation-energy functional, and the LYP variant, are not ideal for the method, since these are universal functionals. Nevertheless, they appear to provide reasonable approximations. The B3LYP functional is derived using a linear combination of two functionals: One is the BLYP functional; the other uses exact exchange and a correlation-energy functional from the LDA.Comment: 26 Pages, 0 figures, RevTeX 4, Submitted to Mol. Phy

Holographic metastability

We show how supersymmetric QCD in a slice of AdS can naturally acquire metastable vacua. The formulation closely follows that of Intriligator, Seiberg and Shih (ISS), with an "electric" sector on the UV brane and a "magnetic" sector on the IR brane. However the 't Hooft anomaly matching that constrains the Seiberg duality central to ISS is replaced by anomaly inflow and cancellation, and the source of strong coupling is the CFT to which the theory couples rather than the gauge groups. The theory contains an anomaly free R-symmetry that, when broken by UV effects, leads to an O'Raifeartaigh model on the IR brane. In contrast to ISS, the R-symmetry breaking in the UV can be maximal, and yet the R-symmetry breaking in the IR theory remains under strict control: there is no need for retrofitting of small parameters.Comment: 20 pages, 2 figure

Light Higgsino in Heavy Gravitino Scenario with Successful Electroweak Symmetry Breaking

We consider, in the context of the minimal supersymmetric standard model, the case where the gravitino weighs 10^6 GeV or more, which is preferred by various cosmological difficulties associated with unstable gravitinos. Despite the large Higgs mixing parameter B together with the little hierarchy to other soft supersymmetry breaking masses, a light higgsino with an electroweak scale mass leads to successful electroweak symmetry breaking, at the price of fine-tuning the higgsino mixing mu parameter. Furthermore the light higgsinos produced at the decays of gravitinos can constitute the dark matter of the universe. The heavy squark mass spectrum of O(10^4) GeV can increase the Higgs boson mass to about 125 GeV or higher.Comment: 13 pages, 3 figures; v2: version to appear in JHE

Cosmological vacuum selection and metastable susy breaking

We study gauge mediation in a wide class of O'Raifeartaigh type models where supersymmetry breaking metastable vacuum is created by gravity and/or quantum corrections. We examine their thermal evolution in the early universe and the conditions under which the susy breaking vacuum can be selected. It is demonstrated that thermalization typically makes the metastable supersymmetry breaking cosmologically disfavoured but this is not always the case. Initial conditions with the spurion displaced from the symmetric thermal minimum and a small coupling to the messenger sector can result in the realization of the susy breaking vacuum even if the reheating temperature is high. We show that this can be achieved without jeopardizing the low energy phenomenology. In addition, we have found that deforming the models by a supersymmetric mass term for messengers in such a way that the susy breaking minimum and the susy preserving minima are all far away from the origin does not change the conclusions. The basic observations are expected to hold also in the case of models with an anomalous U(1) group.Comment: 28 pages, 4 figures, plain Latex, journal versio

Electrostatics in a simple wormhole revisited

The electrostatic potential generated by a point charge at rest in a simple static, spherically symmetric wormhole is given in the form of series of multipoles and in closed form. The general potential which is physically acceptable depends on a parameter due to the fact that the monopole solution is arbitrary. When the wormhole has Z2-symmetry, the potential is completely determined. The calculation of the electrostatic self-energy and of the self-force is performed in all cases considered.Comment: 16 pages, no figure

Fine Tuning in General Gauge Mediation

We study the fine-tuning problem in the context of general gauge mediation. Numerical analyses toward for relaxing fine-tuning are presented. We analyse the problem in typical three cases of the messenger scale, that is, GUT ($2\times10^{16}$ GeV), intermediate ($10^{10}$ GeV), and relatively low energy ($10^6$ GeV) scales. In each messenger scale, the parameter space reducing the degree of tuning as around 10% is found. Certain ratios among gluino mass, wino mass and soft scalar masses are favorable. It is shown that the favorable region becomes narrow as the messenger scale becomes lower, and tachyonic initial conditions of stop masses at the messenger scale are favored to relax the fine-tuning problem for the relatively low energy messenger scale. Our spectra would also be important from the viewpoint of the $\mu-B$ problem.Comment: 22 pages, 16 figures, comment adde

Condensate cosmology in O'Raifeartaigh models

Flat directions charged under an R-symmetry are a generic feature of O'Raifeartaigh models. Non-topological solitons associated with this symmetry, R-balls, are likely to form through the fragmentation of a condensate, itself created by soft terms induced during inflation. In gravity mediated SUSY breaking R-balls decay to gravitinos, reheating the universe. For gauge mediation R-balls can provide a good dark matter candidate. Alternatively they can decay, either reheating or cooling the universe. Conserved R-symmetry permits decay to gravitinos or gauginos, whereas spontaneously broken R-symmetry results in decay to visible sector gauge bosons.Comment: 29 pages, 5 figures. Comments and references added, accepted for publication in JHE