889 research outputs found
Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma.
DICER1 is a critical gene in the biogenesis of mature microRNAs, short non-coding RNAs that derive from either -3p or -5p precursor microRNA strands. Germline mutations of DICER1 are associated with a range of human malignancies, including pleuropulmonary blastoma (PPB). Additional somatic 'hotspot' mutations in the microRNA processing ribonuclease IIIb (RNase IIIb) domain of DICER1 are reported in cancer, and which affect microRNA biogenesis, resulting in a -3p mature microRNA strand bias. Here, in a germline (exon11 c.1806_1810insATTGA) DICER1-mutated PPB, we first confirmed the presence of an additional somatic RNase IIIb hotspot mutation (exon25 c.5425G>A [p.G1809R]) by conventional sequencing. Second, we investigated serum levels of mature microRNAs at the time of PPB diagnosis, and compared the findings with serum results from a comprehensive range of pediatric cancer patients and controls (n=52). We identified a panel of 45 microRNAs that were present at elevated levels in the serum at the time of PPB diagnosis, with a significant majority noted be derived from the -3p strand (P=0.013). In addition, we identified a subset of 10 serum microRNAs (namely miR-125a-3p, miR-125b-2-3p, miR-380-5p, miR-125b-1-3p, let-7f-2-3p, let-7a-3p, let-7b-3p, miR-708-3p, miR-138-1-3p and miR-532-3p) that were most abundant in the PPB case. Serum levels of two representative microRNAs, miR-125a-3p and miR-125b-2-3p, were not elevated in DICER1 germline-mutated relatives. In the PPB case, serum levels of miR-125a-3p and miR-125b-2-3p increased before chemotherapy, and then showed an early reduction following treatment. These microRNAs may offer future utility as serum biomarkers for screening patients with known germline DICER1 mutations for early detection of PPB, and for potential disease-monitoring in cases with confirmed PPB.We would like to thank the following for providing financial support: SPARKS (NC, MJM), Medical Research Council Fellowship (MJM), TD Bank/LDI scholarship (LdK), Alex’s Lemonade Stand Foundation (WDF), Cancer Research UK (NC) and European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 310018 (MT).This is the final published version. It first appeared at http://www.nature.com/oncsis/journal/v3/n2/full/oncsis20141a.html
Three-dimensional heterostructure of metallic nanoparticles and carbon nanotubes as potential nanofiller
The effect of the dimensionality of metallic nanoparticle-and carbon nanotube-based fillers on the mechanical properties of an acrylonitrile butadiene styrene (ABS) polymer matrix was examined. ABS composite films, reinforced with low dimensional metallic nanoparticles (MNPs, 0-D) and carbon nanotubes (CNTs, 1-D) as nanofillers, were fabricated by a combination of wet phase inversion and hot pressing. The tensile strength and elongation of the ABS composite were increased by 39% and 6%, respectively, by adding a mixture of MNPs and CNTs with a total concentration of 2 wt%. However, the tensile strength and elongation of the ABS composite were found to be significantly increased by 62% and 55%, respectively, upon addition of 3-D heterostructures with a total concentration of 2 wt%. The 3-D heterostructures were composed of multiple CNTs grown radially on the surface of MNP cores, resembling a sea urchin. The mechanical properties of the ABS/3-D heterostructured nanofiller composite films were much improved compared to those of an ABS/mixture of 0-D and 1-D nanofillers composite films at various filler concentrations. This suggests that the 3-D heterostructure of the MNPs and CNTs plays a key role as a strong reinforcing agent in supporting the polymer matrix and simultaneously serves as a discrete force-transfer medium to transfer the loaded tension throughout the polymer matrix
Phase Structure and Compactness
In order to study the influence of compactness on low-energy properties, we
compare the phase structures of the compact and non-compact two-dimensional
multi-frequency sine-Gordon models. It is shown that the high-energy scaling of
the compact and non-compact models coincides, but their low-energy behaviors
differ. The critical frequency at which the sine-Gordon model
undergoes a topological phase transition is found to be unaffected by the
compactness of the field since it is determined by high-energy scaling laws.
However, the compact two-frequency sine-Gordon model has first and second order
phase transitions determined by the low-energy scaling: we show that these are
absent in the non-compact model.Comment: 21 pages, 5 figures, minor changes, final version, accepted for
publication in JHE
Global Analysis of the Higgs Candidate with Mass ~ 125 GeV
We analyze the properties of the Higgs candidate with mass ~ 125 GeV
discovered by the CMS and ATLAS Collaborations, constraining the possible
deviations of its couplings from those of a Standard Model Higgs boson. The
CMS, ATLAS and Tevatron data are compatible with Standard Model couplings to
massive gauge bosons and fermions, and disfavour several types of composite
Higgs models unless their couplings resemble those in the Standard Model. We
show that the couplings of the Higgs candidate are consistent with a linear
dependence on particle masses, scaled by the electroweak scale ~ 246 GeV, the
power law and the mass scale both having uncertainties ~ 20%.Comment: 22 pages, 9 figures, v2 incorporates experimental data released
during July 2012 and corrected (and improved) treatment of mass dependence of
coupling
Composite Higgs Sketch
The coupling of a composite Higgs to the standard model fields can deviate
substantially from the standard model values. In this case perturbative
unitarity might break down before the scale of compositeness is reached, which
would suggest that additional composites should lie well below this scale. In
this paper we account for the presence of an additional spin 1 custodial
triplet of rhos. We examine the implications of requiring perturbative
unitarity up to the compositeness scale and find that one has to be close to
saturating certain unitarity sum rules involving the Higgs and the rho
couplings. Given these restrictions on the parameter space we investigate the
main phenomenological consequences of the spin 1 triplet. We find that they can
substantially enhance the Higgs di-photon rate at the LHC even with a reduced
Higgs coupling to gauge bosons. The main existing LHC bounds arise from
di-boson searches, especially in the experimentally clean channel where the
charged rhos decay to a W-boson and a Z, which then decay leptonically. We find
that a large range of interesting parameter space with 700 GeV < m(rho) < 2 TeV
is currently experimentally viable.Comment: 37 pages, 12 figures; v4: sum rule corrected, conclusions unchange
Results of the treatment of bone metastases with modular prosthetic replacement—analysis of 67 patients
Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania
Background: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude.
Methodology/Principal Findings: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0–0.085) for G. swynnertoni and 0% (0–0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0–0.054) and 0.0089% (0–0.059) respectively, and by model inference 0.0064% and 0.00085% respectively.
Conclusions/Significance: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data
Dispersion of carbon nanotubes in polyamide 6 for microinjection moulding
The focus of this study was to investigate the
dispersion state of pure and functionalized carbon nanotubes in polyamide 6, on composites prepared by twin-screw extrusion and then processed by microinjection moulding. Nanocomposites were prepared with different carbonvnanotube compositions, with and without functionalization. The nanotubes were functionalized by the 1,3-dipolar cycloaddition reaction. The dispersion of the carbon nanotube agglomerates was quantified using optical microscopy and image analysis. The effect of functionalization on the polyamide 6/carbon nanotube interface, the nanocomposite morphology and the mechanical and electrical properties were studied. It was observed that the microinjected composites with functionalized carbon nanotubes presented improved dispersion, with smaller carbon nanotube agglomerate area ratio compared to the composites with pure nanotubes. The functionalized nanotubes showed better adhesion to polyamide 6 compared to pure nanotubes, as observed by scanning electron microscopy. The incorporation of carbon nanotubes considerably improved the mechanical properties. The effect of high polymer shear rate on carbon nanotube alignment during microinjection moulding was assessed by comparing the electrical resistivity of the composite after extrusion and after microinjection moulding, through the thickness and along the flow direction. The experiments showed that the mould design and processing conditions significantly affected electrical resistivity.Fundação para a Ciência e Tecnologia (project PEst-C/CTM/LA0025/2013
Phenomenology and Cosmology of an Electroweak Pseudo-Dilaton and Electroweak Baryons
In many strongly-interacting models of electroweak symmetry breaking the
lowest-lying observable particle is a pseudo-Goldstone boson of approximate
scale symmetry, the pseudo-dilaton. Its interactions with Standard Model
particles can be described using a low-energy effective nonlinear chiral
Lagrangian supplemented by terms that restore approximate scale symmetry,
yielding couplings of the pseudo-dilaton that differ from those of a Standard
Model Higgs boson by fixed factors. We review the experimental constraints on
such a pseudo-dilaton in light of new data from the LHC and elsewhere. The
effective nonlinear chiral Lagrangian has Skyrmion solutions that may be
identified with the `electroweak baryons' of the underlying
strongly-interacting theory, whose nature may be revealed by the properties of
the Skyrmions. We discuss the finite-temperature electroweak phase transition
in the low-energy effective theory, finding that the possibility of a
first-order electroweak phase transition is resurrected. We discuss the
evolution of the Universe during this transition and derive an
order-of-magnitude lower limit on the abundance of electroweak baryons in the
absence of a cosmological asymmetry, which suggests that such an asymmetry
would be necessary if the electroweak baryons are to provide the cosmological
density of dark matter. We revisit estimates of the corresponding
spin-independent dark matter scattering cross section, with a view to direct
detection experiments.Comment: 34 pages, 4 figures, additional references adde
Composite GUTs: models and expectations at the LHC
We investigate grand unified theories (GUTs) in scenarios where electroweak
(EW) symmetry breaking is triggered by a light composite Higgs, arising as a
Nambu-Goldstone boson from a strongly interacting sector. The evolution of the
standard model (SM) gauge couplings can be predicted at leading order, if the
global symmetry of the composite sector is a simple group G that contains the
SM gauge group. It was noticed that, if the right-handed top quark is also
composite, precision gauge unification can be achieved. We build minimal
consistent models for a composite sector with these properties, thus
demonstrating how composite GUTs may represent an alternative to supersymmetric
GUTs. Taking into account the new contributions to the EW precision parameters,
we compute the Higgs effective potential and prove that it realizes
consistently EW symmetry breaking with little fine-tuning. The G group
structure and the requirement of proton stability determine the nature of the
light composite states accompanying the Higgs and the top quark: a coloured
triplet scalar and several vector-like fermions with exotic quantum numbers. We
analyse the signatures of these composite partners at hadron colliders:
distinctive final states contain multiple top and bottom quarks, either alone
or accompanied by a heavy stable charged particle, or by missing transverse
energy.Comment: 55 pages, 13 figures, final version to be published in JHE
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