263 research outputs found
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
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