Nanoporous membrane-sealed microfluidic devices for improved cell viability

Abstract Cell-laden microfluidic devices have broad potential in various biomedical applications, including tissue engineering and drug discovery. However, multiple difficulties encountered while culturing cells within devices affecting cell viability, proliferation, and behavior has complicated their use. While active perfusion systems have been used to overcome the diffusive limitations associated with nutrient delivery into microchannels to support longer culture times, these systems can result in non-uniform oxygen and nutrient delivery and subject cells to shear stresses, which can affect cell behavior. Additionally, histological analysis of cell cultures within devices is generally laborious and yields inconsistent results due to difficulties in delivering labeling agents in microchannels. Herein, we describe a simple, cost-effective approach to preserve cell viability and simplify labeling within microfluidic networks without the need for active perfusion. Instead of bonding a microfluidic network to glass, PDMS, or other solid substrate, the network is bonded to a semipermeable nanoporous membrane. The membrane-sealed devices allow free exchange of proteins, nutrients, buffers, and labeling reagents between the microfluidic channels and culture media in static culture plates under sterile conditions. The use of the semi-permeable membrane dramatically simplifies microniche cell culturing while avoiding many of the complications which arise from perfusion systems

Enhanced structural correlations accelerate diffusion in charge-stabilized colloidal suspensions

Theoretical calculations for colloidal charge-stabilized and hard sphere suspensions show that hydrodynamic interactions yield a qualitatively different particle concentration dependence of the short-time self-diffusion coefficient. The effect, however, is numerically small and hardly accessible by conventional light scattering experiments. Applying multiple-scattering decorrelation equipment and a careful data analysis we show that the theoretical prediction for charged particles is in agreement with our experimental results from aqueous polystyrene latex suspensions.Comment: 1 ps-file (MS-Word), 14 page

Lithium in the Intermediate-Age Open Cluster, NGC 3680

High-dispersion spectra centered on the Li 6708 A line have been obtained for 70 potential members of the open cluster NGC 3680, with an emphasis on stars in the turnoff region. A measurable Li abundance has been derived for 53 stars, 39 of which have radial velocities and proper motions consistent with cluster membership. After being transferred to common temperature and abundance scales, previous Li estimates have been combined to generate a sample of 49 members, 40 of which bracket the cluster Li-dip. Spectroscopic elemental analysis of 8 giants and 5 turnoff stars produces [Fe/H] = -0.17 +/- 0.07 (sd) and -0.07 +/- 0.02 (sd), respectively. We also report measurements of Ca, Si and Ni which are consistent with scaled-solar ratios within the errors. Adopting [Fe/H] = -0.08 (Sect. 3.6), Y^2 isochrone comparisons lead to an age of 1.75 +/- 0.10 Gyr and an apparent modulus of (m-M) = 10.30 +/- 0.15 for the cluster, placing the center of the Li-dip at 1.35 +/- 0.03 solar masses. Among the giants, 5 of 9 cluster members are now known to have measurable Li with A(Li) near 1.0. A combined sample of dwarfs in the Hyades and Praesepe is used to delineate the Li-dip profile at 0.7 Gyr and [Fe/H] = +0.15, establishing its center at 1.42 +/- 0.02 solar masses and noting the possible existence of secondary dip on its red boundary. When evolved to the typical age of the clusters NGC 752, IC 4651 and NGC 3680, the Hyades/Praesepe Li-dip profile reproduces the observed morphology of the combined Li-dip within the CMD's of the intermediate-age clusters while implying a metallicity dependence for the central mass of the Li-dip given by Mass = (1.38 +/-0.04) + (0.4 +/- 0.2)[Fe/H]. The implications of the similarity of the Li-dichotomy among giants in NGC 752 and IC 4651 and the disagreement with the pattern among NGC 3680 giants are discussed.Comment: Latex ms. is 56 pages, including 10 figures and 4 tables. Accepted for the Astronomical Journa

Absolute dimensions of the unevolved B-type eclipsing binary GG Orionis

We present photometric observations in B and V as well as spectroscopic observations of the detached, eccentric 6.6-day double-lined eclipsing binary GG Ori, a member of the Orion OB1 association. Absolute dimensions of the components, which are virtually identical, are determined to high accuracy (better than 1% in the masses and better than 2% in the radii) for the purpose of testing various aspects of theoretical modeling. We obtain M(A) = 2.342 +/- 0.016 solar masses and R(A) = 1.852 +/- 0.025 solar radii for the primary, and M(B) = 2.338 +/- 0.017 solar masses and R(B) = 1.830 +/- 0.025 solar radii for the secondary. The effective temperature of both stars is 9950 +/- 200 K, corresponding to a spectral type of B9.5. GG Ori is very close to the ZAMS, and comparison with current stellar evolution models gives ages of 65-82 Myr or 7.7 Myr depending on whether the system is considered to be burning hydrogen on the main sequence or still in the final stages of pre-main sequence contraction. We have detected apsidal motion in the binary at a rate of dw/dt = 0.00061 +/- 0.00025 degrees per cycle, corresponding to an apsidal period of U = 10700 +/- 4500 yr. A substantial fraction of this (approximately 70%) is due to the contribution from General Relativity.Comment: To appear in The Astronomical Journal, December 200

Obliquities of Hot Jupiter host stars: Evidence for tidal interactions and primordial misalignments

We provide evidence that the obliquities of stars with close-in giant planets were initially nearly random, and that the low obliquities that are often observed are a consequence of star-planet tidal interactions. The evidence is based on 14 new measurements of the Rossiter-McLaughlin effect (for the systems HAT-P-6, HAT-P-7, HAT-P-16, HAT-P-24, HAT-P-32, HAT-P-34, WASP-12, WASP-16, WASP-18, WASP-19, WASP-26, WASP-31, Gl 436, and Kepler-8), as well as a critical review of previous observations. The low-obliquity (well-aligned) systems are those for which the expected tidal timescale is short, and likewise the high-obliquity (misaligned and retrograde) systems are those for which the expected timescale is long. At face value, this finding indicates that the origin of hot Jupiters involves dynamical interactions like planet-planet interactions or the Kozai effect that tilt their orbits, rather than inspiraling due to interaction with a protoplanetary disk. We discuss the status of this hypothesis and the observations that are needed for a more definitive conclusion.Comment: Accepted for publication in ApJ; typos corrected, 2 broken references fixed, 26 pages, 25 figure

AGEMAP: A Gene Expression Database for Aging in Mice

We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project) gene expression database, which is a resource that catalogs changes in gene expression as a function of age in mice. The AGEMAP database includes expression changes for 8,932 genes in 16 tissues as a function of age. We found great heterogeneity in the amount of transcriptional changes with age in different tissues. Some tissues displayed large transcriptional differences in old mice, suggesting that these tissues may contribute strongly to organismal decline. Other tissues showed few or no changes in expression with age, indicating strong levels of homeostasis throughout life. Based on the pattern of age-related transcriptional changes, we found that tissues could be classified into one of three aging processes: (1) a pattern common to neural tissues, (2) a pattern for vascular tissues, and (3) a pattern for steroid-responsive tissues. We observed that different tissues age in a coordinated fashion in individual mice, such that certain mice exhibit rapid aging, whereas others exhibit slow aging for multiple tissues. Finally, we compared the transcriptional profiles for aging in mice to those from humans, flies, and worms. We found that genes involved in the electron transport chain show common age regulation in all four species, indicating that these genes may be exceptionally good markers of aging. However, we saw no overall correlation of age regulation between mice and humans, suggesting that aging processes in mice and humans may be fundamentally different

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm

Inhibition of Adaptive Immune Responses Leads to a Fatal Clinical Outcome in SIV-Infected Pigtailed Macaques but Not Vervet African Green Monkeys

African green monkeys (AGM) and other natural hosts for simian immunodeficiency virus (SIV) do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIVagmVer90 to infect vervet AGM and pigtailed macaques (PTM). This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM) but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4) and AGM (n = 4), and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms