Characterizing upward lightning with and without a terrestrial gamma-ray flash

We compare two observations of gamma-rays before, during, and after lightning flashes initiated by upward leaders from a tower during low-altitude winter thunderstorms on the western coast of Honshu, Japan. While the two leaders appear similar, one produced a terrestrial gamma-ray flash (TGF) so bright that it paralyzed the gamma-ray detectors while it was occurring, and could be observed only via the weaker flux of neutrons created in its wake, while the other produced no detectable TGF gamma-rays at all. The ratio between the indirectly derived gamma-ray fluence for the TGF and the 95% confidence gamma-ray upper limit for the gamma-ray quiet flash is a factor of $1\times10^7$. With the only two observations of this type providing such dramatically different results -- a TGF probably as bright as those seen from space and a powerful upper limit -- we recognize that weak, sub-luminous TGFs in this situation are probably not common, and we quantify this conclusion. While the gamma-ray quiet flash appeared to have a faster leader and more powerful initial continuous current pulse than the flash that produced a TGF, the TGF-producing flash occurred during a weak gamma-ray "glow", while the gamma-ray quiet flash did not, implying a higher electric field aloft when the TGF was produced. We suggest that the field in the high-field region approached by a leader may be more important for whether a TGF is produced than the characteristics of the leader itself.Comment: 21 pages, 6 figures, accepted for publication by the Journal of Geophysical Research - Atmosphere

Mouse models for preeclampsia: disruption of redox-regulated signaling

The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

Development of a cadmium telluride pixel detector for astrophysical applications

We are developing imaging Cadmium Telluride (CdTe) pixel detectors optimized for astrophysical hard X-ray applications. Our hybrid detector consist of a CdTe crystal 1mm thick and 2cm × 2cm in area with segmented anode contacts directly bonded to a custom low-noise application specific integrated circuit (ASIC). The CdTe sensor, fabricated by ACRORAD (Okinawa, Japan), has Schottky blocking contacts on a 605 micron pitch in a 32 × 32 array, providing low leakage current and enabling readout of the anode side. The detector is bonded using epoxy-gold stud interconnects to a custom low noise, low power ASIC circuit developed by Caltech's Space Radiation Laboratory. We have achieved very good energy resolution over a wide energy range (0.62keV FWHM @ 60keV, 10.8keV FWHM @ 662keV). We observe polarization effects at room temperature, but they are suppressed if we operate the detector at or below 0°C degree. These detectors have potential application for future missions such as the International X-ray Observatory (IXO)

Quantum magneto-optics of graphite family

The optical conductivity of graphene, bilayer graphene, and graphite in quantizing magnetic fields is studied. Both dynamical conductivities, longitudinal and Hall's, are analytically evaluated. The conductivity peaks are explained in terms of electron transitions. We have shown that trigonal warping can be considered within the perturbation theory for strong magnetic fields larger than 1 T and in the semiclassical approach for weak fields when the Fermi energy is much larger than the cyclotron frequency. The main optical transitions obey the selection rule with \Deltan = 1 for the Landau number n, however the \Deltan = 2 transitions due to the trigonal warping are also possible. The Faraday/Kerr rotation and light transmission/reflection in the quantizing magnetic fields are calculated. Parameters of the Slonczewski-Weiss-McClure model are used in the fit taking into account the previous dHvA measurements and correcting some of them for the case of strong magnetic fields.Comment: 28 pages, 12 figures. arXiv admin note: text overlap with arXiv:1106.340

Restricted feedback control of one-dimensional maps

Dynamical control of biological systems is often restricted by the practical constraint of unidirectional parameter perturbations. We show that such a restriction introduces surprising complexity to the stability of one-dimensional map systems and can actually improve controllability. We present experimental cardiac control results that support these analyses. Finally, we develop new control algorithms that exploit the structure of the restricted-control stability zones to automatically adapt the control feedback parameter and thereby achieve improved robustness to noise and drifting system parameters.Comment: 29 pages, 9 embedded figure

Grb2 depletion under non-stimulated conditions inhibits PTEN, promotes Akt-induced tumor formation and contributes to poor prognosis in ovarian cancer

In the absence of extracellular stimulation the adaptor protein growth factor receptor-bound protein (Grb2) and the phospholipase Plcγ1 compete for the same binding site on fibroblast growth factor receptor 2 (FGFR2). Reducing cellular Grb2 results in upregulation of Plcγ1 and depletion of the phospholipid PI(4,5)P2. The functional consequences of this event on signaling pathways are unknown. We show that the decrease in PI(4,5)P2 level under non-stimulated conditions inhibits PTEN activity leading to the aberrant activation of the oncoprotein Akt. This results in excessive cell proliferation and tumor progression in a xenograft mouse model. As well as defining a novel mechanism of Akt phosphorylation with important therapeutic consequences, we also demonstrate that differential expression levels of FGFR2, Plcγ1 and Grb2 correlate with patient survival. Oncogenesis through fluctuation in the expression levels of these proteins negates extracellular stimulation or mutation and defines them as novel prognostic markers in ovarian cancer

Attenuation of doxorubicin-induced cardiotoxicity by mdivi-1: a mitochondrial division/mitophagy inhibitor

Doxorubicin is one of the most effective anti-cancer agents. However, its use is associated with adverse cardiac effects, including cardiomyopathy and progressive heart failure. Given the multiple beneficial effects of the mitochondrial division inhibitor (mdivi-1) in a variety of pathological conditions including heart failure and ischaemia and reperfusion injury, we investigated the effects of mdivi-1 on doxorubicin-induced cardiac dysfunction in naïve and stressed conditions using Langendorff perfused heart models and a model of oxidative stress was used to assess the effects of drug treatments on the mitochondrial depolarisation and hypercontracture of cardiac myocytes. Western blot analysis was used to measure the levels of p-Akt and p-Erk 1/2 and flow cytometry analysis was used to measure the levels p-Drp1 and p-p53 upon drug treatment. The HL60 leukaemia cell line was used to evaluate the effects of pharmacological inhibition of mitochondrial division on the cytotoxicity of doxorubicin in a cancer cell line. Doxorubicin caused a significant impairment of cardiac function and increased the infarct size to risk ratio in both naïve conditions and during ischaemia/reperfusion injury. Interestingly, co-treatment of doxorubicin with mdivi-1 attenuated these detrimental effects of doxorubicin. Doxorubicin also caused a reduction in the time taken to depolarisation and hypercontracture of cardiac myocytes, which were reversed with mdivi-1. Finally, doxorubicin caused a significant elevation in the levels of signalling proteins p-Akt, p-Erk 1/2, p-Drp1 and p-p53. Co-incubation of mdivi-1 with doxorubicin did not reduce the cytotoxicity of doxorubicin against HL-60 cells. These data suggest that the inhibition of mitochondrial fission protects the heart against doxorubicin-induced cardiac injury and identify mitochondrial fission as a new therapeutic target in ameliorating doxorubicin-induced cardiotoxicity without affecting its anti-cancer properties