The Evershed Effect with SOT/Hinode

The Solar Optical Telescope onboard Hinode revealed the fine-scale structure of the Evershed flow and its relation to the filamentary structures of the sunspot penumbra. The Evershed flow is confined in narrow channels with nearly horizontal magnetic fields, embedded in a deep layer of the penumbral atmosphere. It is a dynamic phenomenon with flow velocity close to the photospheric sound speed. Individual flow channels are associated with tiny upflows of hot gas (sources) at the inner end and downflows (sinks) at the outer end. SOT/Hinode also discovered ``twisting'' motions of penumbral filaments, which may be attributed to the convective nature of the Evershed flow. The Evershed effect may be understood as a natural consequence of thermal convection under a strong, inclined magnetic field. Current penumbral models are discussed in the lights of these new Hinode observations.Comment: To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Les Houches 2015: Physics at TeV colliders - new physics working group report

We present the activities of the 'New Physics' working group for the 'Physics at TeV Colliders' workshop (Les Houches, France, 1-19 June, 2015). Our report includes new physics studies connected with the Higgs boson and its properties, direct search strategies, reinterpretation of the LHC results in the building of viable models and new computational tool developments. Important signatures for searches for natural new physics at the LHC and new assessments of the interplay between direct dark matter searches and the LHC are also considered.Comment: Proceedings of the New Physics Working Group of the 2015 Les Houches Workshop, Physics at TeV Colliders, Les Houches 1-19 June 2015. 197 page

A systems approach to model natural variation in reactive properties of bacterial ribosomes

<p>Abstract</p> <p>Background</p> <p>Natural variation in protein output from translation in bacteria and archaea may be an organism-specific property of the ribosome. This paper adopts a systems approach to model the protein output as a measure of specific ribosome reactive properties in a ribosome-mediated translation apparatus. We use the steady-state assumption to define a transition state complex for the ribosome, coupled with mRNA, tRNA, amino acids and reaction factors, as a subsystem that allows a focus on the completed translational output as a measure of specific properties of the ribosome.</p> <p>Results</p> <p>In analogy to the steady-state reaction of an enzyme complex, we propose a steady-state translation complex for mRNA from any gene, and derive a maximum specific translation activity, <it>T</it>_{<it>a</it>(max)}, as a property of the ribosomal reaction complex. <it>T</it>_{<it>a</it>(max)}has units of <it>a</it>-protein output per time per <it>a</it>-specific mRNA. A related property of the ribosome, <inline-formula><m:math name="1752-0509-2-62-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:msub><m:mover accent="true"><m:mi>T</m:mi><m:mo>˜</m:mo></m:mover><m:mrow><m:mi>a</m:mi><m:mo stretchy="false">(</m:mo><m:mi>max</m:mi><m:mo>⁡</m:mo><m:mo stretchy="false">)</m:mo></m:mrow></m:msub></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmivaqLbaGaadaWgaaWcbaGaemyyaeMaeiikaGIagiyBa0MaeiyyaeMaeiiEaGNaeiykaKcabeaaaaa@3464@</m:annotation></m:semantics></m:math></inline-formula>, has units of <it>a</it>-protein per time per total RNA with the relationship <inline-formula><m:math name="1752-0509-2-62-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:msub><m:mover accent="true"><m:mi>T</m:mi><m:mo>˜</m:mo></m:mover><m:mrow><m:mi>a</m:mi><m:mo stretchy="false">(</m:mo><m:mi>max</m:mi><m:mo>⁡</m:mo><m:mo stretchy="false">)</m:mo></m:mrow></m:msub></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmivaqLbaGaadaWgaaWcbaGaemyyaeMaeiikaGIagiyBa0MaeiyyaeMaeiiEaGNaeiykaKcabeaaaaa@3464@</m:annotation></m:semantics></m:math></inline-formula> = <it>ρ</it>_{<it>a </it>}<it>T</it>_{<it>a</it>(max)}, where <it>ρ</it>_{<it>a </it>}represents the fraction of total RNA committed to translation output of <it>P</it>_{<it>a </it>}from gene <it>a </it>message. <it>T</it>_{<it>a</it>(max)}as a ribosome property is analogous to <it>k</it>_catfor a purified enzyme, and <inline-formula><m:math name="1752-0509-2-62-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:msub><m:mover accent="true"><m:mi>T</m:mi><m:mo>˜</m:mo></m:mover><m:mrow><m:mi>a</m:mi><m:mo stretchy="false">(</m:mo><m:mi>max</m:mi><m:mo>⁡</m:mo><m:mo stretchy="false">)</m:mo></m:mrow></m:msub></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmivaqLbaGaadaWgaaWcbaGaemyyaeMaeiikaGIagiyBa0MaeiyyaeMaeiiEaGNaeiykaKcabeaaaaa@3464@</m:annotation></m:semantics></m:math></inline-formula> is analogous to enzyme specific activity in a crude extract.</p> <p>Conclusion</p> <p>Analogy to an enzyme reaction complex led us to a ribosome reaction model for measuring specific translation activity of a bacterial ribosome. We propose to use this model to design experimental tests of our hypothesis that specific translation activity is a ribosomal property that is subject to natural variation and natural selection much like <it>V</it>_maxand <it>K</it>_mfor any specific enzyme.</p

Convection and the Origin of Evershed Flows

Numerical simulations have by now revealed that the fine scale structure of the penumbra in general and the Evershed effect in particular is due to overturning convection, mainly confined to gaps with strongly reduced magnetic field strength. The Evershed flow is the radial component of the overturning convective flow visible at the surface. It is directed outwards -- away from the umbra -- because of the broken symmetry due to the inclined magnetic field. The dark penumbral filament cores visible at high resolution are caused by the 'cusps' in the magnetic field that form above the gaps. Still remaining to be established are the details of what determines the average luminosity of penumbrae, the widths, lengths, and filling factors of penumbral filaments, and the amplitudes and filling factors of the Evershed flow. These are likely to depend at least partially also on numerical aspects such as limited resolution and model size, but mainly on physical properties that have not yet been adequately determined or calibrated, such as the plasma beta profile inside sunspots at depth and its horizontal profile, the entropy of ascending flows in the penumbra, etc.Comment: 13 pages, 7 figures. To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Development of a Tumor-Selective Approach to Treat Metastatic Cancer

BACKGROUND: Patients diagnosed with metastatic cancer have almost uniformly poor prognoses. The treatments available for patients with disseminated disease are usually not curative and have side effects that limit the therapy that can be given. A treatment that is selectively toxic to tumors would maximize the beneficial effects of therapy and minimize side effects, potentially enabling effective treatment to be administered. METHODS AND FINDINGS: We postulated that the tumor-tropic property of stem cells or progenitor cells could be exploited to selectively deliver a therapeutic gene to metastatic solid tumors, and that expression of an appropriate transgene at tumor loci might mediate cures of metastatic disease. To test this hypothesis, we injected HB1.F3.C1 cells transduced to express an enzyme that efficiently activates the anti-cancer prodrug CPT-11 intravenously into mice bearing disseminated neuroblastoma tumors. The HB1.F3.C1 cells migrated selectively to tumor sites regardless of the size or anatomical location of the tumors. Mice were then treated systemically with CPT-11, and the efficacy of treatment was monitored. Mice treated with the combination of HB1.F3.C1 cells expressing the CPT-11-activating enzyme and this prodrug produced tumor-free survival of 100% of the mice for >6 months (P<0.001 compared to control groups). CONCLUSIONS: The novel and significant finding of this study is that it may be possible to exploit the tumor-tropic property of stem or progenitor cells to mediate effective, tumor-selective therapy for metastatic tumors, for which no tolerated curative treatments are currently available

Plakophilin3 Loss Leads to an Increase in PRL3 Levels Promoting K8 Dephosphorylation, Which Is Required for Transformation and Metastasis

The desmosome anchors keratin filaments in epithelial cells leading to the formation of a tissue wide IF network. Loss of the desmosomal plaque protein plakophilin3 (PKP3) in HCT116 cells, leads to an increase in neoplastic progression and metastasis, which was accompanied by an increase in K8 levels. The increase in levels was due to an increase in the protein levels of the Phosphatase of Regenerating Liver 3 (PRL3), which results in a decrease in phosphorylation on K8. The increase in PRL3 and K8 protein levels could be reversed by introduction of an shRNA resistant PKP3 cDNA. Inhibition of K8 expression in the PKP3 knockdown clone S10, led to a decrease in cell migration and lamellipodia formation. Further, the K8 PKP3 double knockdown clones showed a decrease in colony formation in soft agar and decreased tumorigenesis and metastasis in nude mice. These results suggest that a stabilisation of K8 filaments leading to an increase in migration and transformation may be one mechanism by which PKP3 loss leads to tumor progression and metastasis