Economics and quality attributes of hMSC production in xeno-free bioprocessing media

Human Mesenchymal Stem Cells (hMSCs) are key raw material in Regenerative Medicine and are widely used for therapeutics, engineered tissues, and medical devices. Yet, achieving an economical bioprocess for hMSC production remains a significant challenge for industry. Bioprocess economic modeling highlights media as a major cost driver in cell manufacturing. Hence, the availability of efficient and robust xeno-free bioprocessing media will not only reduce manufacturing cost, but also decrease regulatory burden associated with bovine serum components found in traditional culture media. Here, we evaluated and compared hMSCs quality parameters in bovine serum-containing and xeno-free bioprocess media formulations and assessed quality parameters such as cell identity, potency and functionality. Cells in xeno-free media maintained critical hMSC functional properties including angiogenic cytokine (FGF, HGF, IL8, TIMP1, TIMP2, and VEGF) secretion, trilineage differentiation, and immunomodulatory potential. In addition, hMSCs cultured in xeno-free media expanded rapidly and achieved confluency within 4-5 days of culture without media exchange. The economics of hMSC expansion in this xeno-free media were modeled and compared to other competitive hMSC cell or media systems where it consistently outperformed traditional hMSC systems by more than 8 fold on the critical productivity metric of Million cells per Liter, making it ideal for industrial-scale manufacturing of hMSCs

Disorder-enhanced phase coherence in trapped bosons on optical lattices

The consequences of disorder on interacting bosons trapped in optical lattices are investigated by quantum Monte Carlo simulations. At small to moderate strengths of potential disorder a unique effect is observed: if there is a Mott plateau at the center of the trap in the clean limit, phase coherence {\it increases} as a result of disorder. The localization effects due to correlation and disorder compete against each other, resulting in a partial delocalization of the particles in the Mott region, which in turn leads to increased phase coherence. In the absence of a Mott plateau, this effect is absent. A detailed analysis of the uniform system without a trap shows that the disordered states participate in a Bose glass phase.Comment: 4 pages, 4 figure

High-speed Civil Transport Aircraft Emissions

Estimates are given for the emissions from a proposed high speed civil transport (HSCT). This advanced technology supersonic aircraft would fly in the lower stratosphere at a speed of roughly Mach 1.6 to 3.2 (470 to 950 m/sec or 920 to 1850 knots). Because it would fly in the stratosphere at an altitude in the range of 15 to 23 km commensurate with its design speed, its exhaust effluents could perturb the chemical balance in the upper atmosphere. The first step in determining the nature and magnitude of any chemical changes in the atmosphere resulting from these proposed aircraft is to identify and quantify the chemically important species they emit. Relevant earlier work is summarized, dating back to the Climatic Impact Assessment Program of the early 1970s and current propulsion research efforts. Estimates are provided of the chemical composition of an HSCT's exhaust, and these emission indices are presented. Other aircraft emissions that are not due to combustion processes are also summarized; these emissions are found to be much smaller than the exhaust emissions. Future advances in propulsion technology, in experimental measurement techniques, and in understanding upper atmospheric chemistry may affect these estimates of the amounts of trace exhaust species or their relative importance

Order via Nonlinearity in Randomly Confined Bose Gases

A Hartree-Fock mean-field theory of a weakly interacting Bose-gas in a quenched white noise disorder potential is presented. A direct continuous transition from the normal gas to a localized Bose-glass phase is found which has localized short-lived excitations with a gapless density of states and vanishing superfluid density. The critical temperature of this transition is as for an ideal gas undergoing Bose-Einstein condensation. Increasing the particle-number density a first-order transition from the localized state to a superfluid phase perturbed by disorder is found. At intermediate number densities both phases can coexist.Comment: Author Information under http://www.theo-phys.uni-essen.de/tp/ags/pelster_dir/. International Journal of Bifurcation and Chaos (in press

Mean-field phase diagram of disordered bosons in a lattice at non-zero temperature

Bosons in a periodic lattice with on-site disorder at low but non-zero temperature are considered within a mean-field theory. The criteria used for the definition of the superfluid, Mott insulator and Bose glass are analysed. Since the compressibility does never vanish at non-zero temperature, it can not be used as a general criterium. We show that the phases are unambiguously distinguished by the superfluid density and the density of states of the low-energy exitations. The phase diagram of the system is calculated. It is shown that even a tiny temperature leads to a significant shift of the boundary between the Bose glass and superfluid

Precision atomic gravimeter based on Bragg diffraction

We present a precision gravimeter based on coherent Bragg diffraction of freely falling cold atoms. Traditionally, atomic gravimeters have used stimulated Raman transitions to separate clouds in momentum space by driving transitions between two internal atomic states. Bragg interferometers utilize only a single internal state, and can therefore be less susceptible to environmental perturbations. Here we show that atoms extracted from a magneto-optical trap using an accelerating optical lattice are a suitable source for a Bragg atom interferometer, allowing efficient beamsplitting and subsequent separation of momentum states for detection. Despite the inherently multi-state nature of atom diffraction, we are able to build a Mach-Zehnder interferometer using Bragg scattering which achieves a sensitivity to the gravitational acceleration of $\Delta g/g = 2.7\times10^{-9}$ with an integration time of 1000s. The device can also be converted to a gravity gradiometer by a simple modification of the light pulse sequence.Comment: 13 pages, 11 figure

Making Friends in the Rainforest: Negrito Adaptation to Risk and Uncertainty

The so-called negritos adapt not just to a tropical forest environment but also to an environment characterized by perturbations and fluctuations. As with other hunter-gatherers in the region and, indeed, throughout the world, they use both social and ecological methods to enhance their chances of survival in this changing environment: socially, they have developed networks of trading and marriage partners; ecologically, they maintain patches of key resources that are available for future harvesting. As evidenced in the case of the Batek (Orang Asli), patterns of forest structure and composition are sometimes direct outcomes of intentional resource concentration and enrichment strategies. While little of the above is controversial anthropologically, what has drawn some debate is the nature of the relationship with partner societies. Conventional wisdom posits relations of inequality between foragers and others : foragers and farmers are often construed as hierarchical dyads where foragers supply products or labor to farmers in exchange for agricultural harvests and other trade goods. This kind of adaptation appears to be one of divergent specialization. However, there are cases, such as in the relationship between Batek and Semaq Beri, where both societies follow a roughly similar mode of adaptation, and specialization has not materialized. In sum, while not denying that hierarchy and inequality exist, I suggest that they have to be contextualized within a larger strand of relationships that includes both hierarchy and egality. Further, such relationships are part of the general portfolio of risk reduction strategies, following which access to widely scattered environmental resources, and passage from one location to another, is enhanced not by competing with and displacing neighbors but by maintaining a flexible regime of friendly exchange partners

Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance

Purpose Diagnosis of genetic disorders is hampered by large numbers of variants of uncertain significance (VUSs) identified through next-generation sequencing. Many such variants may disrupt normal RNA splicing. We examined effects on splicing of a large cohort of clinically identified variants and compared performance of bioinformatic splicing prediction tools commonly used in diagnostic laboratories. Methods Two hundred fifty-seven variants (coding and noncoding) were referred for analysis across three laboratories. Blood RNA samples underwent targeted reverse transcription polymerase chain reaction (RT-PCR) analysis with Sanger sequencing of PCR products and agarose gel electrophoresis. Seventeen samples also underwent transcriptome-wide RNA sequencing with targeted splicing analysis based on Sashimi plot visualization. Bioinformatic splicing predictions were obtained using Alamut, HSF 3.1, and SpliceAI software. Results Eighty-five variants (33%) were associated with abnormal splicing. The most frequent abnormality was upstream exon skipping (39/85 variants), which was most often associated with splice donor region variants. SpliceAI had greatest accuracy in predicting splicing abnormalities (0.91) and outperformed other tools in sensitivity and specificity. Conclusion Splicing analysis of blood RNA identifies diagnostically important splicing abnormalities and clarifies functional effects of a significant proportion of VUSs. Bioinformatic predictions are improving but still make significant errors. RNA analysis should therefore be routinely considered in genetic disease diagnostics

Atom laser coherence and its control via feedback

We present a quantum-mechanical treatment of the coherence properties of a single-mode atom laser. Specifically, we focus on the quantum phase noise of the atomic field as expressed by the first-order coherence function, for which we derive analytical expressions in various regimes. The decay of this function is characterized by the coherence time, or its reciprocal, the linewidth. A crucial contributor to the linewidth is the collisional interaction of the atoms. We find four distinct regimes for the linewidth with increasing interaction strength. These range from the standard laser linewidth, through quadratic and linear regimes, to another constant regime due to quantum revivals of the coherence function. The laser output is only coherent (Bose degenerate) up to the linear regime. However, we show that application of a quantum nondemolition measurement and feedback scheme will increase, by many orders of magnitude, the range of interaction strengths for which it remains coherent.Comment: 15 pages, 6 figures, revtex