High resolution temporal transcriptomics of mouse embryoid body development reveals complex expression dynamics of coding and noncoding loci.

Cellular responses to stimuli are rapid and continuous and yet the vast majority of investigations of transcriptional responses during developmental transitions typically use long interval time courses; limiting the available interpretive power. Moreover, such experiments typically focus on protein-coding transcripts, ignoring the important impact of long noncoding RNAs. We therefore evaluated coding and noncoding expression dynamics at unprecedented temporal resolution (6-hourly) in differentiating mouse embryonic stem cells and report new insight into molecular processes and genome organization. We present a highly resolved differentiation cascade that exhibits coding and noncoding transcriptional alterations, transcription factor network interactions and alternative splicing events, little of which can be resolved by long-interval developmental time-courses. We describe novel short lived and cycling patterns of gene expression and dissect temporally ordered gene expression changes in response to transcription factors. We elucidate patterns in gene co-expression across the genome, describe asynchronous transcription at bidirectional promoters and functionally annotate known and novel regulatory lncRNAs. These findings highlight the complex and dynamic molecular events underlying mammalian differentiation that can only be observed though a temporally resolved time course

Albedo and laser threshold of a diffusive Raman gain medium

The diffuse reflectance (albedo) and transmittance of a Raman random gain medium are calculated via semi-analytic two-stream equations with power-dependent coefficients. The results show good agreement with the experimental data for barium nitrate powder. Both the Raman albedo AR and Raman transmittance TR diverge at a critical gain gc, interpreted as the threshold for diffusive Raman laser generation. However, the ratio TR/AR approaches a finite limiting value dependent on particle scattering albedo v and scattering asymmetry g. The dependence of the generation threshold on the scattering parameters is analysed and the feedback effect of Fresnel reflection at the gain boundaries evaluated. The addition of external mirrors, particularly at the pumped surface, significantly reduces the threshold gain.Comment: 15 pages, 8 figure

Cosmic D-Strings and Vortons in Supergravity

Recent developments in string inspired models of inflation suggest that D-strings are formed at the end of inflation. Within the supergravity model of D-strings there are 2(n-1) chiral fermion zero modes for a D-string of winding n. Using the bounds on the relic vorton density, we show that D-strings with winding number n>1 are more strongly constrained than cosmic strings arising in cosmological phase transitions. The D-string tension of such vortons, if they survive until the present, has to satisfy 8\pi G_N \mu \lesssim p 10^{-26} where p is the intercommutation probability. Similarly, D-strings coupled with spectator fermions carry currents and also need to respect the above bound. D-strings with n=1 do not carry currents and evade the bound. We discuss the coupling of D-strings to supersymmetry breaking. When a single U(1) gauge group is present, we show that there is an incompatibility between spontaneous supersymmetry breaking and cosmic D-strings. We propose an alternative mechanism for supersymmetry breaking, which includes an additional U(1), and might alleviate the problem. We conjecture what effect this would have on the fermion zero modes.Comment: 11 page

Statistical mechanics of triangulated ribbons

We use computer simulations and scaling arguments to investigate statistical and structural properties of a semiflexible ribbon composed of isosceles triangles. We study two different models, one where the bending energy is calculated from the angles between the normal vectors of adjacent triangles, the second where the edges are viewed as semiflexible polymers so that the bending energy is related to the angles between the tangent vectors of next-nearest neighbor triangles. The first model can be solved exactly whereas the second is more involved. It was recently introduced by Liverpool and Golestanian Phys.Rev.Lett. 80, 405 (1998), Phys.Rev.E 62, 5488 (2000) as a model for double-stranded biopolymers such as DNA. Comparing observables such as the autocorrelation functions of the tangent vectors and the bond-director field, the probability distribution functions of the end-to-end distance, and the mean squared twist we confirm the existence of local twist correlation, but find no indications for other predicted features such as twist-stretch coupling, kinks, or oscillations in the autocorrelation function of the bond-director field.Comment: 10 pages, 13 figures. submitted to PRE, revised versio

Samarium-153 labelled microparticles for liver tumour targeted therapy with imaging functionality

Samarium-153 (153Sm) are widely used in radia-tion synovectomy and pain management for patients with bone metastases. However, its therapeutic application has not been fully explored. 153Sm has been proven to be useful for imaging purposes. This provides a beneficial alternative for therapy with pure beta emitter especially for liver radioembolization with Yttrium-90 (90Y). This study aimed to develop an alterna-tive radioembolic agent using 153Sm and biocompatible resin microparticles for liver cancer therapy. The ion-exchange resin; Amberlite IR-120 H+ commercially available in large beads were crushed and sieved to 20 – 40 μm and labelled with 152SmCl3 salt prior to neutron activation. Administered activity of 3 GBq 153Sm was aimed based on the standard activity used by the 90Y SIR-Spheres. 6 hours irradiation in 1.494 x 1012 n.cm-2.s-1 flux produced 3.1 GBq.g-1 immediately after activa-tion. Characterization of the microparticles, gamma spectros-copy, and in-vitro radiolabelling studies were carried out and compared to a commercially available resin readily made in 20 – 40 μm, Fractogel EMD SO3- (S). 153Sm-Amberlite micropar-ticles possess a superior and suitable characteristics for liver radioembolization with added imaging capabilities

Cosmic Vortons and Particle Physics Constraints

We investigate the cosmological consequences of particle physics theories that admit stable loops of superconducting cosmic string - {\it vortons}. General symmetry breaking schemes are considered, in which strings are formed at one energy scale and subsequently become superconducting in a secondary phase transition at what may be a considerably lower energy scale. We estimate the abundances of the ensuing vortons, and thereby derive constraints on the relevant particle physics models from cosmological observations. These constraints significantly restrict the category of admissible Grand Unified theories, but are quite compatible with recently proposed effects whereby superconducting strings may have been formed close to the electroweak phase transition.Comment: 33 pages, 2 figures, RevTe

Stealth Branes

We discuss the brane world model of Dvali, Gabadadze and Porrati in which branes evolve in an infinite bulk and the brane curvature term is added to the action. If Z_2 symmetry between the two sides of the brane is not imposed, we show that the model admits the existence of "stealth branes" which follow the standard 4D internal evolution and have no gravitational effect on the bulk space. Stealth branes can nucleate spontaneosly in a Minkowski bulk. This process is described by the standard 4D quantum cosmology formalism with tunneling boundary conditions for the brane world wave function. The notorious ambiguity in the choice of boundary conditions is fixed in this case due to the presence of the embedding spacetime. We also point to some problematic aspects of models admitting stealth brane solutions.Comment: 24 pages; Final version, to appear in Phys. Rev. D. The discussion of "embeddability obstruction" is removed (thanks to Takahiro Tanaka who convinced us that there is no such obstruction

Microphysics of SO(10) Cosmic Strings

We uncover a rich microphysical structure for SO(10) cosmic strings. For the abelian string the electroweak symmetry is restored around it in a region depending on the electroweak scale. A rich structure of nonabelian strings is found. Some of these also restore the electroweak symmetry. We investigate the zero mode structure of our strings. Whilst there are right handed neutrino zero modes for the abelian string, they do not survive the electroweak phase transition. In general the nonabelian strings do not have fermion zero modes. We consider the generalisation of our results to other theories and consider cosmological consequences of them.Comment: 34 pages, LATEX. Replaced version is restructured, and has small correction to fermion zero mode analysis. To be published in Physical Review

Boron Phosphide Films by Reactive Sputtering Searching for a P Type Transparent Conductor

With an indirect band gap in the visible and a direct band gap at a much higher energy, boron phosphide BP holds promise as an unconventional p type transparent conductor. This work reports on reactive sputtering of amorphous BP films, their partial crystallization in a P containing annealing atmosphere, and extrinsic doping by C and Si. The highest hole concentration to date for p type BP 5 1020 cm amp; 8722;3 is achieved using C doping under B rich conditions. Furthermore, bipolar doping is confirmed to be feasible in BP. An anneal temperature of at least 1000 C is necessary for crystallization and dopant activation. Hole mobilities are low and indirect optical transitions are stronger than that predicted by theory. Low crystalline quality probably plays a role in both cases. High figures of merit for transparent conductors might be achievable in extrinsically doped BP films with improved crystalline qualit

Acute myeloid leukemia maturation lineage influences residual disease and relapse following differentiation therapy

Acute myeloid leukemia (AML) is a malignancy of immature progenitor cells. AML differentiation therapies trigger leukemia maturation and can induce remission, but relapse is prevalent and its cellular origin is unclear. Here we describe high resolution analysis of differentiation therapy response and relapse in a mouse AML model. Triggering leukemia differentiation in this model invariably produces two phenotypically distinct mature myeloid lineages in vivo. Leukemia-derived neutrophils dominate the initial wave of leukemia differentiation but clear rapidly and do not contribute to residual disease. In contrast, a therapyinduced population of mature AML-derived eosinophil-like cells persists during remission, often in extramedullary organs. Using genetic approaches we show that restricting therapy induced leukemia maturation to the short-lived neutrophil lineage markedly reduces relapse rates and can yield cure. These results indicate that relapse can originate from therapy resistant mature AML cells, and suggest differentiation therapy combined with targeted eradication of mature leukemia-derived lineages may improve disease outcome.Steven Ngo, Ethan P. Oxley, Margherita Ghisi, Maximilian M. Garwood, Mark D. McKenzie, Helen L. Mitchell, Peter Kanellakis, Olivia Susanto, Michael J. Hickey, Andrew C. Perkins, Benjamin T. Kile, Ross A. Dickin