Activation of pluripotency genes in human fibroblast cells by a novel mRNA based approach

Background: Several methods have been used to induce somatic cells to re-enter the pluripotent state. Viral transduction of reprogramming genes yields higher efficiency but involves random insertions of viral sequences into the human genome. Although induced pluripotent stem (iPS) cells can be obtained with the removable PiggyBac transposon system or an episomal system, both approaches still use DNA constructs so that resulting cell lines need to be thoroughly analyzed to confirm they are free of harmful genetic modification. Thus a method to change cell fate without using DNA will be very useful in regenerative medicine. Methodology/Principal Findings: In this study, we synthesized mRNAs encoding OCT4, SOX2, cMYC, KLF4 and SV40 large T (LT) and electroporated them into human fibroblast cells. Upon transfection, fibroblasts expressed these factors at levels comparable to, or higher than those in human embryonic stem (ES) cells. Ectopically expressed OCT4 localized to the cell nucleus within 4 hours after mRNA introduction. Transfecting fibroblasts with a mixture of mRNAs encoding all five factors significantly increased the expression of endogenous OCT4, NANOG, DNMT3 beta, REX1 and SALL4. When such transfected fibroblasts were also exposed to several small molecules (valproic acid, BIX01294 and 5'-aza-2'-deoxycytidine) and cultured in human embryonic stem cell (ES) medium they formed small aggregates positive for alkaline phosphatase activity and OCT4 protein within 30 days. Conclusion/Significance: Our results demonstrate that mRNA transfection can be a useful approach to precisely control the protein expression level and short-term expression of reprogramming factors is sufficient to activate pluripotency genes in differentiated cells

Auroral Cluster: A Space Physics Mission for Multiple, Electronically Tethered Small Satellites

Auroral Cluster is a space physics mission that has been identified by the NASA Space Physics Strategic Implementation Study as a candidate for flight in the next decade. Auroral Cluster will employ multiple spacecraft outfitted with similar complements of science instruments allowing simultaneous multipoint plasma measurements in the Earth\u27s auroral regions. Co-orbiting small satellites (mass \u3c 400 kg each) that are electronically tethered to share distributed spacecraft systems represent an efficient approach for achieving the science goals of the Auroral Cluster mission. Multisatellite missions represent a new trend in gathering space science data and pose many new and difficult challenges for the space systems engineer. The results of an Auroral Cluster feasibility study, which discusses a variety of mission trade-offs, are presented. A discussion of the science background and mission goals is used to identify the technical drivers for the design of the multiple spacecraft system. A mission plan and some considerations for a Auroral Cluster satellite design are presented. Special consideration is given to the spacecraft subsystems that will allow the system to be operated as a network of electronically tethered interdependent small satellites. These subsystems include attitude determination, spatial separation knowledge and control, data storage, and intersatellite communication

Advance telephone calls ahead of reminder questionnaires increase response rate in non-responders compared to questionnaire reminders only : The RECORD phone trial

Peer reviewedPublisher PD

On the Properties of Special Functions on the linear-type lattices

We present a general theory for studying the difference analogues of special functions of hypergeometric type on the linear-type lattices, i.e., the solutions of the second order linear difference equation of hypergeometric type on a special kind of lattices: the linear type lattices. In particular, using the integral representation of the solutions we obtain several difference-recurrence relations for such functions. Finally, applications to $q$-classical polynomials are given

Ramanujan and Extensions and Contractions of Continued Fractions

If a continued fraction $K_{n=1}^{\infty} a_{n}/b_{n}$ is known to converge but its limit is not easy to determine, it may be easier to use an extension of $K_{n=1}^{\infty}a_{n}/b_{n}$ to find the limit. By an extension of $K_{n=1}^{\infty} a_{n}/b_{n}$ we mean a continued fraction $K_{n=1}^{\infty} c_{n}/d_{n}$ whose odd or even part is $K_{n=1}^{\infty} a_{n}/b_{n}$. One can then possibly find the limit in one of three ways: (i) Prove the extension converges and find its limit; (ii) Prove the extension converges and find the limit of the other contraction (for example, the odd part, if $K_{n=1}^{\infty}a_{n}/b_{n}$ is the even part); (ii) Find the limit of the other contraction and show that the odd and even parts of the extension tend to the same limit. We apply these ideas to derive new proofs of certain continued fraction identities of Ramanujan and to prove a generalization of an identity involving the Rogers-Ramanujan continued fraction, which was conjectured by Blecksmith and Brillhart.Comment: 16 page

Cropping system effects on soil quality in the Great Plains: Synthesis from a regional project

Soils perform a number of essential functions affecting management goals. Soil functions were assessed by measuring physical, chemical, and biological properties in a regional assessment of conventional (CON) and alternative (ALT) management practices at eight sites within the Great Plains. The results, reported in accompanying papers, provide excellent data for assessing how management practices collectively affect agronomic and environmental soil functions that benefit both farmers and society. Our objective was to use the regional data as an input for two new assessment tools to evaluate their potential and sensitivity for detecting differences (aggradation or degradation) in management systems. The soil management assessment framework (SMAF) and the agro-ecosystem performance assessment tool (AEPAT) were used to score individual soil properties at each location relative to expected conditions based on inherent soil-forming factors and to compute index values that provide an overall assessment of the agronomic and environmental impact of the CON and ALT practices. SMAF index values were positively correlated with grain yield (an agronomic function) and total organic matter (an agronomic and environmental function). They were negatively correlated with soil nitrate concentration at harvest (an indicator of environmental function). There was general agreement between the two assessment tools when used to compare management practices. Users can measure a small number of soil properties and use one of these tools to easily assess the effectiveness of soil management practices. A higher score in either tool identifies more environmentally and agronomically sustainable management. Temporal variability in measured indicators makes dynamic assessments of management practices essential. Water-filled pore space, aggregate stability, particulate organic matter, and microbial biomass were sensitive to management and should be included in studies aimed at improving soil management. Reductions in both tillage and fallow combined with crop rotation has resulted in improved soil function (e.g., nutrient cycling, organic C content, and productivity) throughout the Great Plains

On the complete analytic structure of the massive gravitino propagator in four-dimensional de Sitter space

With the help of the general theory of the Heun equation, this paper completes previous work by the authors and other groups on the explicit representation of the massive gravitino propagator in four-dimensional de Sitter space. As a result of our original contribution, all weight functions which multiply the geometric invariants in the gravitino propagator are expressed through Heun functions, and the resulting plots are displayed and discussed after resorting to a suitable truncation in the series expansion of the Heun function. It turns out that there exist two ranges of values of the independent variable in which the weight functions can be divided into dominating and sub-dominating family.Comment: 21 pages, 9 figures. The presentation has been further improve

Dilogarithm Identities in Conformal Field Theory and Group Homology

Recently, Rogers' dilogarithm identities have attracted much attention in the setting of conformal field theory as well as lattice model calculations. One of the connecting threads is an identity of Richmond-Szekeres that appeared in the computation of central charges in conformal field theory. We show that the Richmond-Szekeres identity and its extension by Kirillov-Reshetikhin can be interpreted as a lift of a generator of the third integral homology of a finite cyclic subgroup sitting inside the projective special linear group of all $2 \times 2$ real matrices viewed as a {\it discrete} group. This connection allows us to clarify a few of the assertions and conjectures stated in the work of Nahm-Recknagel-Terhoven concerning the role of algebraic $K$-theory and Thurston's program on hyperbolic 3-manifolds. Specifically, it is not related to hyperbolic 3-manifolds as suggested but is more appropriately related to the group manifold of the universal covering group of the projective special linear group of all $2 \times 2$ real matrices viewed as a topological group. This also resolves the weaker version of the conjecture as formulated by Kirillov. We end with the summary of a number of open conjectures on the mathematical side.Comment: 20 pages, 2 figures not include

Non-destructive, dynamic detectors for Bose-Einstein condensates

We propose and analyze a series of non-destructive, dynamic detectors for Bose-Einstein condensates based on photo-detectors operating at the shot noise limit. These detectors are compatible with real time feedback to the condensate. The signal to noise ratio of different detection schemes are compared subject to the constraint of minimal heating due to photon absorption and spontaneous emission. This constraint leads to different optimal operating points for interference-based schemes. We find the somewhat counter-intuitive result that without the presence of a cavity, interferometry causes as much destruction as absorption for optically thin clouds. For optically thick clouds, cavity-free interferometry is superior to absorption, but it still cannot be made arbitrarily non-destructive . We propose a cavity-based measurement of atomic density which can in principle be made arbitrarily non-destructive for a given signal to noise ratio

Order Parameters of the Dilute A Models

The free energy and local height probabilities of the dilute A models with broken \Integer_2 symmetry are calculated analytically using inversion and corner transfer matrix methods. These models possess four critical branches. The first two branches provide new realisations of the unitary minimal series and the other two branches give a direct product of this series with an Ising model. We identify the integrable perturbations which move the dilute A models away from the critical limit. Generalised order parameters are defined and their critical exponents extracted. The associated conformal weights are found to occur on the diagonal of the relevant Kac table. In an appropriate regime the dilute A$_3$ model lies in the universality class of the Ising model in a magnetic field. In this case we obtain the magnetic exponent $\delta=15$ directly, without the use of scaling relations.Comment: 53 pages, LaTex, ITFA 93-1