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

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

A Geometric Approach to CP Violation: Applications to the MCPMFV SUSY Model

We analyze the constraints imposed by experimental upper limits on electric dipole moments (EDMs) within the Maximally CP- and Minimally Flavour-Violating (MCPMFV) version of the MSSM. Since the MCPMFV scenario has 6 non-standard CP-violating phases, in addition to the CP-odd QCD vacuum phase \theta_QCD, cancellations may occur among the CP-violating contributions to the three measured EDMs, those of the Thallium, neutron and Mercury, leaving open the possibility of relatively large values of the other CP-violating observables. We develop a novel geometric method that uses the small-phase approximation as a starting point, takes the existing EDM constraints into account, and enables us to find maximal values of other CP-violating observables, such as the EDMs of the Deuteron and muon, the CP-violating asymmetry in b --> s \gamma decay, and the B_s mixing phase. We apply this geometric method to provide upper limits on these observables within specific benchmark supersymmetric scenarios, including extensions that allow for a non-zero \theta_QCD.Comment: 34 pages, 16 eps figures, to appear in JHE

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

CP violation in sbottom decays

We study CP asymmetries in two-body decays of bottom squarks into charginos and tops. These asymmetries probe the SUSY CP phases of the sbottom and the chargino sector in the Minimal Supersymmetric Standard Model. We identify the MSSM parameter space where the CP asymmetries are sizeable, and analyze the feasibility of their observation at the LHC. As a result, potentially detectable CP asymmetries in sbottom decays are found, which motivates further detailed experimental studies for probing the SUSY CP phases.Comment: 29 pages, 7 figure

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

Removal of ecotoxicity of 17α-ethinylestradiol using TAML/peroxide water treatment

17α -ethinylestradiol (EE2), a synthetic oestrogen in oral contraceptives, is one of many pharmaceuticals found in inland waterways worldwide as a result of human consumption and excretion into wastewater treatment systems. At low parts per trillion (ppt), EE2 induces feminisation of male fish, diminishing reproductive success and causing fish population collapse. Intended water quality standards for EE2 set a much needed global precedent. Ozone and activated carbon provide effective wastewater treatments, but their energy intensities and capital/operating costs are formidable barriers to adoption. Here we describe the technical and environmental performance of a fast- developing contender for mitigation of EE2 contamination of wastewater based upon smallmolecule, full-functional peroxidase enzyme replicas called “TAML activators”. From neutral to basic pH, TAML activators with H2O2 efficiently degrade EE2 in pure lab water, municipal effluents and EE2-spiked synthetic urine. TAML/H2O2 treatment curtails estrogenicity in vitro and substantially diminishes fish feminization in vivo. Our results provide a starting point for a future process in which tens of thousands of tonnes of wastewater could be treated per kilogram of catalyst. We suggest TAML/H2O2 is a worthy candidate for exploration as an environmentally compatible, versatile, method for removing EE2 and other pharmaceuticals from municipal wastewaters.Heinz Endowments, the Swiss National Science Foundation, the Steinbrenner Institute for a Steinbrenner Doctoral Fellowship. NMR instrumentation at CMU was partially supported by NSF (CHE-0130903 and CHE-1039870)