Cold atmospheric pressure plasma jets:Interaction with plasmid DNA and tailored electron heating using dual-frequency excitation

Recent progress in plasma science and technology has enabled the development of a new generation of stable cold non-equilibrium plasmas operating at ambient atmospheric pressure. This opens horizons for new plasma technologies, in particular in the emerging field of plasma medicine. These non-equilibrium plasmas are very efficient sources for energy transport through reactive neutral particles (radicals and metastables), charged particles (ions and electrons), UV radiation, and electro-magnetic fields. The effect of a cold radio frequency-driven atmospheric pressure plasma jet on plasmid DNA has been investigated. The formation of double strand breaks correlates well with the atomic oxygen density. Taken with other measurements, this indicates that neutral components in the jet are effective in inducing double strand breaks. Plasma manipulation techniques for controlled energy delivery are highly desirable. Numerical simulations are employed for detailed investigations of the electron dynamics, which determines the generation of reactive species. New concepts based on nonlinear power dissipation promise superior strategies to control energy transport for tailored technological exploitations. © 2012 American Institute of Physics.

A theoretical assessment of surface defect machining and hot machining of nanocrystalline silicon carbide

In this paper, a newly proposed machining method named “surface defect machining” (SDM) [Wear, 302, 2013 (1124-1135)] was explored for machining of nanocrystalline beta silicon carbide (3C-SiC) at 300K using MD simulation. The results were compared with isothermal high temperature machining at 1200K under the same machining parameters, emulating ductile mode micro laser assisted machining (µ-LAM) and with conventional cutting at 300 K. In the MD simulation, surface defects were generated on the top of the (010) surface of the 3C-SiC work piece prior to cutting, and the workpiece was then cut along the <100> direction using a single point diamond tool at a cutting speed of 10 m/sec. Cutting forces, sub-surface deformation layer depth, temperature in the shear zone, shear plane angle and friction coefficient were used to characterize the response of the workpiece. Simulation results showed that SDM provides a unique advantage of decreased shear plane angle which eases the shearing action. This in turn causes an increased value of average coefficient of friction in contrast to the isothermal cutting (carried at 1200 K) and normal cutting (carried at 300K). The increase of friction coefficient however was found to aid the cutting action of the tool due to an intermittent dropping in the cutting forces, lowering stresses on the cutting tool and reducing operational temperature. Analysis shows that the introduction of surface defects prior to conventional machining can be a viable choice for machining a wide range of ceramics, hard steels and composites compared to hot machining.

Investigation into the radiobiological consequences of pre-treatment verification imaging with megavoltage X-rays in radiotherapy

Objective: The aim of this study was to investigate the effect of pre-treatment verification imaging with megavoltage (MV) X-rays on cancer and normal cell survival in vitro and to compare the findings with theoretically modelled data. Since the dose received from pre-treatment imaging can be significant, incorporation of this dose at the planning stage of treatment has been suggested.

Methods: The impact of imaging dose incorporation on cell survival was investigated by clonogenic assay, irradiating DU-145 prostate cancer, H460 non-small cell lung cancer and AGO-1522b normal tissue fibroblast cells. Clinically relevant imaging-to-treatment times of 7.5 minutes and 15 minutes were chosen for this study. The theoretical magnitude of the loss of radiobiological efficacy due to sublethal damage repair was investigated using the Lea-Catcheside dose protraction factor model.

Results: For the cell lines investigated, the experimental data showed that imaging dose incorporation had no significant impact upon cell survival. These findings were in close agreement with the theoretical results.

Conclusions: For the conditions investigated, the results suggest that allowance for the imaging dose at the planning stage of treatment should not adversely affect treatment efficacy.

Advances in Knowledge: There is a paucity of data in the literature on imaging effects in radiotherapy. This paper presents a systematic study of imaging dose effects on cancer and normal cell survival, providing both theoretical and experimental evidence for clinically relevant imaging doses and imaging-to-treatment times. The data provide a firm foundation for further study into this highly relevant area of research.

Low-energy scattering of electrons by caesium atoms

The relativistic R-matrix method is used to calculate elastic and inelastic cross sections for electrons incident on caesium atoms with energies from 0-3 eV. These cross sections reveal a wealth of resonance structure in this energy range. The differential cross sections as well as the spin polarisation function S( theta ) and the left-right asymmetry function S( theta ) are calculated and enable conclusions to be drawn on the importance of spin-dependent interactions.

Low-energy scattering of electrons by caesium atoms. II

The relativistic R-matrix method is used to calculate elastic and inelastic cross sections for electrons incident on caesium atoms with energies from 0-3 eV. In addition to the total cross sections, results are presented on the differential cross sections, sigma , and the spin polarisation, P, of the scattered electrons as a function of energy at the scattering angles 10 degrees , 50 degrees , 90 degrees and 150 degrees . The calculation reveals a wealth of resonances around the P and P thresholds. The resonances are analysed in detail and their role in the scattering process is discussed.

Enabling ultra high precision on hard steels using surface defect machining

This paper is an extension to an idea coined during the 13th EUSPEN Conference (P6.23) named "surface defect machining" (SDM). The objective of this work was to demonstrate how a conventional CNC turret lathe can be used to obtain ultra high precision machined surface finish on hard steels without recourse to a sophisticated ultra precision machine tool. An AISI 4340 hard steel (69 HRC) workpiece was machined using a CBN cutting tool with and without SDM. Post-machining measurements by a Form Talysurf and a Scanning Electron Microscope (FEI Quanta 3D) revealed that SDM culminates to several key advantages (i) provides better quality of the machined surface integrity and offers (ii) lowering feed rate to 5μm/rev to obtain a machined surface roughness of 30 nm (optical quality).

When terror hits home: Identity Fused Americans who saw Boston bombing victims as “family” provided aid

When tragedy strikes a group, only some group members characteristically rush to the aid of the victims. What motivates the altruism of these exceptional individuals? Here, we provide one set of answers based on data collected before and shortly after the 15 April 2013, Boston Marathon bombings. The results of three studies indicated that Americans who were strongly “fused” with their country were especially inclined to provide various forms of support to the bombing victims. Moreover, the degree to which participants reported perceiving fellow Americans as psychological kin statistically mediated links between fusion and pro-group outcomes. Together, these findings shed new light on relationships between personal and group identity, cognitive representations of group members, and personally costly, pro-group actions.

Gold nanoparticle cellular uptake, toxicity and radiosensitisation in hypoxic conditions

Background and purpose: Gold nanoparticles (GNPs) are novel agents that have been shown to cause radiosensitisation in vitro and in vivo. Tumour hypoxia is associated with radiation resistance and reduced survival in cancer patients. The interaction of GNPs with cells in hypoxia is explored.

Materials and methods: GNP uptake, localization, toxicity and radiosensitisation were assessed in vitro under oxic and hypoxic conditions.

Results: GNP cellular uptake was significantly lower under hypoxic than oxic conditions. A significant reduction in cell proliferation in hypoxic MDA-MB-231 breast cancer cells exposed to GNPs was observed. In these cells significant radiosensitisation occurred in normoxia and moderate hypoxia. However, in near anoxia no significant sensitisation occurred.

Conclusions: GNP uptake occurred in hypoxic conditions, causing radiosensitisation in moderate, but not extreme hypoxia in a breast cancer cell line. These findings may be important for the development of GNPs for cancer therapy.

Prediction of surface roughness during hard turning of AISI 4340 steel (69 HRC)

In this study, 39 sets of hard turning (HT) experimental trials were performed on a Mori-Seiki SL-25Y (4-axis) computer numerical controlled (CNC) lathe to study the effect of cutting parameters in influencing the machined surface roughness. In all the trials, AISI 4340 steel workpiece (hardened up to 69 HRC) was machined with a commercially available CBN insert (Warren Tooling Limited, UK) under dry conditions. The surface topography of the machined samples was examined by using a white light interferometer and a reconfirmation of measurement was done using a Form Talysurf. The machining outcome was used as an input to develop various regression models to predict the average machined surface roughness on this material. Three regression models - Multiple regression, Random Forest, and Quantile regression were applied to the experimental outcomes. To the best of the authors’ knowledge, this paper is the first to apply Random Forest or Quantile regression techniques to the machining domain. The performance of these models was compared to each other to ascertain how feed, depth of cut, and spindle speed affect surface roughness and finally to obtain a mathematical equation correlating these variables. It was concluded that the random forest regression model is a superior choice over multiple regression models for prediction of surface roughness during machining of AISI 4340 steel (69 HRC).

Parametric design optimization of hard turning of AISI 4340 steel (69 HRC)

Continuous research endeavors on hard turning (HT), both on machine tools and cutting tools, have made the previously reported daunting limits easily attainable in the modern scenario. This presents an opportunity for a systematic investigation on finding the current attainable limits of hard turning using a CNC turret lathe. Accordingly, this study aims to contribute to the existing literature by providing the latest experimental results of hard turning of AISI 4340 steel (69 HRC) using a CBN cutting tool. An orthogonal array was developed using a set of judiciously chosen cutting parameters. Subsequently, the longitudinal turning trials were carried out in accordance with a well-designed full factorial-based Taguchi matrix. The speculation indeed proved correct as a mirror finished optical quality machined surface (an average surface roughness value of 45 nm) was achieved by the conventional cutting method. Furthermore, Signal-to-noise (S/N) ratio analysis, Analysis of variance (ANOVA), and Multiple regression analysis were carried out on the experimental datasets to assert the dominance of each machining variable in dictating the machined surface roughness and to optimize the machining parameters. One of the key findings was that when feed rate during hard turning approaches very low (about 0.02mm/rev), it could alone be most significant (99.16%) parameter in influencing the machined surface roughness (Ra). This has, however also been shown that low feed rate results in high tool wear, so the selection of machining parameters for carrying out hard turning must be governed by a trade-off between the cost and quality considerations.

Radiosensitising Nanoparticles as Novel Cancer Therapeutics — Pipe Dream or Realistic Prospect?

The field of high atomic number nanoparticle radiosensitising agents is reviewed. After a brief discussion of the new mode of physicochemical action implied by irradiation of high atomic number nanoparticles embedded in biological systems, a series of exemplars are discussed. Silver-, gadolinium- and gold-based nanoparticles are discussed in order of increasing atomic number with functionalisation strategies being outlined. In vitro and in vivo evidence for radio-enhancement and the mechanisms attributed to the increased biological effect are discussed.

Intravitreal AAV2.COMP-Ang1 prevents neurovascular degeneration in a murine model of diabetic retinopathy

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in the United States. The vision-threatening processes of neuroglial and vascular dysfunction in DR occur in concert, driven by hyperglycemia and propelled by a pathway of inflammation, ischemia, vasodegeneration, and breakdown of the blood retinal barrier. Currently, no therapies exist for normalizing the vasculature in DR. Here we show that a single intravitreal dose of adeno-associated virus serotype 2 encoding a more stable, soluble, and potent form of angiopoietin 1 (AAV2.COMP-Ang1) can ameliorate the structural and functional hallmarks of DR in Ins2Akita mice, with sustained effects observed through six months. In early DR, AAV2.COMP-Ang1 restored leukocyte-endothelial interaction, retinal oxygenation, vascular density, vascular marker expression, vessel permeability, retinal thickness, inner retinal cellularity, and retinal neurophysiological response to levels comparable to non-diabetic controls. In late DR, AAV2.COMP-Ang1 enhanced the therapeutic benefit of intravitreally-delivered endothelial colony-forming cells by promoting their integration into the vasculature and thereby stemming further visual decline. AAV2.COMP-Ang1 single-dose gene therapy can prevent neurovascular pathology, support vascular regeneration, and stabilize vision in DR.

Novel role of androgens in mitochondrial fission and apoptosis

Androgen and androgen receptors (AR) play critical roles in the proliferation of prostate cancer through transcriptional regulation of target genes. Here, we found that androgens upregulated the expression of dynamin-related protein 1 (Drp1), which is involved in the induction of mitochondrial fission, a common event in mitosis and apoptosis. Clinical tissue samples and various prostate cancer cell lines revealed a positive correlation between Drp1 and AR levels. Treatment of androgen-sensitive cells with an AR agonist, R1881, and antagonist, bicalutamide, showed that Drp1 is transcriptionally regulated by androgens, as confirmed by an AR ChIP-seq assay. Live imaging experiments using pAcGFP1-Mito stably transfected LNCaP (mito-green) cells revealed that androgen did not induce significant mitochondrial fission by itself, although Drp1 was upregulated. However, when treated with CGP37157 (CGP), an inhibitor of mitochondrial Ca²⁺ efflux, these cells exhibited mitochondrial fission, which was further enhanced by pretreatment with R1881, suggesting that androgen-induced Drp1 expression facilitated CGP-induced mitochondrial fission. This enhanced mitochondrial fission was correlated with increased apoptosis. Transfection with dominant-negative (DN-Drp1, K38A) rescued cells from increased apoptosis, confirming the role of androgen-induced Drp1 in the observed apoptosis with combination treatment. Furthermore, we found that CGP reduced the expression of Mfn1, a protein that promotes mitochondrial fusion, a process which opposes fission. We suggest that androgen-increased Drp1 enhanced mitochondrial fission leading to apoptosis. The present study shows a novel role for androgens in the regulation of mitochondrial morphology that could potentially be utilized in prostate cancer therapy.