The radiation-inducible pE9 promoter driving inducible nitric oxide synthase radiosensitizes hypoxic tumour cells to radiation

Driving high-level transgene expression in a tumour-specific manner remains a key requirement in the development of cancer gene therapy. We have previously demonstrated the strong anticancer effects of generating abnormally high levels of intracellular NO• following the overexpression of the inducible nitric oxide synthase (iNOS) gene. Much of this work has focused on utilizing exogenously activated promoters, which have been primarily induced using X-ray radiation. Here we further examine the potential of the pE9 promoter, comprising a combination of nine CArG radio-responsive elements, to drive the iNOS transgene. Effects of X-ray irradiation on promoter activity were compared in vitro under normoxic conditions and various degrees of hypoxia. The pE9 promoter generated high-level transgene expression, comparable with that achieved using the constitutively driven cytomegalovirus promoter. Furthermore, the radio-resistance of radiation-induced fibrosarcoma-1 (RIF-1) mouse sarcoma cells exposed to 0.1 and 0.01% O2 was effectively eliminated following transfection with the pE9/iNOS construct. Significant inhibition of tumour growth was also observed in vivo following direct intratumoural injection of the pE9/iNOS construct compared to empty vector alone (P<0.001) or to a single radiation dose of 10?Gy (P<0.01). The combination of both therapies resulted in a significant 4.25 day growth delay compared to the gene therapy treatment alone (P<0.001). In summary, we have demonstrated the potential of the pE9/iNOS construct for reducing radio-resistance conferred by tumour cell hypoxia in vitro and in vivo, with greater tumour growth delay observed following the treatment with the gene therapy construct as compared with radiotherapy alone.

The influence of the relative phase between the driving voltages on electron heating in asymmetric dual frequency capacitive discharges

The influence of the relative phase between the driving voltages on electron heating in asymmetric phase-locked dual frequency capacitively coupled radio frequency plasmas operated at 2 and 14 MHz is investigated. The basis of the analysis is a nonlinear global model with the option to implement a relative phase between the two driving voltages. In recent publications it has been reported that nonlinear electron resonance heating can drastically enhance the power dissipation to electrons at moments of sheath collapse due to the self-excitation of nonlinear plasma series resonance (PSR) oscillations of the radio frequency current. This work shows that depending on the relative phase of the driving voltages, the total number and exact moments of sheath collapse can be influenced. In the case of two consecutive sheath collapses a substantial increase in dissipated power compared with the known increase due to a single PSR excitation event per period is observed. Phase resolved optical emission spectroscopy (PROES) provides access to the excitation dynamics in front of the driven electrode. Via PROES the propagation of beam-like energetic electrons immediately after the sheath collapse is observed. In this work we demonstrate that there is a close relation between moments of sheath collapse, and thus excitation of the PSR, and beam-like electron propagation. A comparison of simulation results to experiments in a single and dual frequency discharge shows good agreement. In particular the observed influence of the relative phase on the dynamics of a dual frequency discharge is described by means of the presented model. Additionally, the analysis demonstrates that the observed gain in dissipation is not accompanied by an increase in the electrode’s dc-bias voltage which directly addresses the issue of separate control of ion flux and ion energy in dual frequency capacitively coupled radio frequency plasmas.

Millimeter-wave stealth radio for special operations forces

For Special Operations Forces, an important attribute of any future radio will be the ability to conceal transmissions from the enemy while transmitting large amounts of data for situational awareness and communications. These requirements will mean that military wireless systems designers will need to consider operating frequencies in the mm-wave bands: The high data rates that are achievable at these frequencies and the propagation characteristics at this wavelength will provide many benefits for the implementation of 'stealth radio'. This article discusses some of the recent advances in RF front-end technology, alongside physical layer transmission schemes that could be employed for millimeter-wave soldier-mounted radio. The operation of a hypothetical millimeter-wave soldier-to-soldier communications system that makes use of smart antenna technology is also described.

Nonconservative generalized current-induced forces

A recent result for the curl of forces on ions under steady-state current in atomic wires with noninteracting electrons is extended to generalized forces on classical degrees of freedom in the presence of mean-field electron-electron screening. Current is described within a generic multiterminal picture, forces within the Ehrenfest approximation, and screening within an adiabatic, but not necessarily spatially local, mean-field picture.

Nonconservative current-induced forces: A physical interpretation

We give a physical interpretation of the recently demonstrated non-conservative nature of interatomic forces in current-carrying nanostructures. We start from the analytical expression for the curl of these forces, and evaluate it for a point defect in a current-carrying system. We obtain a general definition of the capacity of electrical current flow to exert a non-conservative force, and thus do net work around closed paths, by a formal non-invasive test procedure. Second, we show that the gain in atomic kinetic energy in time, generated by non-conservative current-induced forces, is equivalent to the uncompensated stimulated emission of directional phonons. This connection with electron-phonon interactions quantifies explicitly the intuitive notion that non-conservative forces work by angular momentum transfer.

A comparison of the strengths of gastropod shells with forces generated by potential crab predators

Carcinus manenas, Liocarcinus puber and Cancer pagurs are thought to be three likely crab predators of the gastropod Calliostoma Zizyphinum. In order to compare the strenghts of predators and their prey, the whole shell and aperture lip strengh of white and pink Calliostoma morphotypes and the maximum forces exerted by the chelipeds of three crab species were measured. Although white shells were thicker than pink shells, Calliostoma colour morphotyes did not differ significantly in either the force required to break the shell lip or the whole shell. Both Liocarcinus puber and Carcinus maenas have dimorphic chelipeds and their “crusher” chelipeds deliver almost double the forces generated by the‘cutter’chelipeds. In constrast, Cancer pagurus has monomorphic chelipeds both delivering similar forces. When compared with Calliostoma shell strenght, the forces generated by the‘crusher’chelipeds of most L. puber tested were, in general, sufficient to break the shell lip of Calliostoma shells, whereas forces generated by the‘cutter’chelipeds of only the larger individuals were sufficient to break the shell lip. In C. manenas, forces generated by both the‘cutter’and‘crusher’chelipeds often exceeded the minimum recorded force required to break the shell lip and the‘crusher’cheliped reached the minimum force required to break whole Calliostoma shells. Both chelipeds of all C. pagurus tested generated forces in excess of the minimum required to break the shell lip, and the proportion of individuals capable of generating the minimum force required to break the whole shell increased with the size of the size of the crab. Carcinus maenas and Cancer pagurus were capable of breaking both the shell lips and the whole shells of a wider range of shell sizes than L. puber.