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The current coronavirus pandemic has resulted in an unprecedented acceleration of online instruction, particularly in the form of e-learning, yet there has not been a commensurate movement exploring the role of study within a digital context. While e-learning seeks to replicate analog learning practices that result in measurable outcomes, e-study presents an alternative educational logic. E-study embraces the rhizomatic dimensions of the internet to foster singular educational experiences devoid of progress indicators, engaging with the digital on its own terms while revealing new potentialities. This article posits that these potentialities are actualized through studious drift, a yielding to a flow beyond one’s control that results in an ongoing process of stupification. The authors use the occasion of an experiment titled Studio_D to provide a framework for creating digital spaces that provoke studious drift and demonstrate its potential.

BACKGROUND: Holistic approach to the clinical management pathway for malignancy of undefined primary origin (MUO)/carcinoma of unknown primary (CUP) patients remains an unmet clinical need. To address this, an MUO/CUP service was implemented during conception of a new acute oncology service (AOS). METHODOLOGY: Over a comparable 17 months’ duration, patient outcomes pre-MUO/CUP service implementation was retrospectively analysed and compared prospectively with post-service implementation database. Performance measures of MUO/CUP service were compared against national recommendations. RESULTS: In the retrospective cohort (n=32), median age was 71.5 years and median length of hospital stay (LOS) was 11.25 days. In the prospective cohort (n=42), median age was 75.5 years, median LOS was 7.75 days (p=0.037). Post-service implementation, 100% patients were discussed in MUO/CUP multidisciplinary team meeting; 96% of inpatient referrals were reviewed by oncology within 24–48 hours. In the prospective group, median overall survival (OS) was 73 days vs 35 days in the retrospective group (p=0.045; hazard ratio (HR) 1.61). Out of 20 patients suitable for anti-cancer treatment in the prospective group, 85% were treated within 31 days from the decision-to-treat; 90% were treated within 62 days of referral. Within the prospective group, median OS was 214 days in the treated sub-group, compared with 44 days in patients receiving best supportive care only (p

Engineering the redox cofactor metabolism is known to be a key challenge in developing a platform strain for biosynthesis of valuable products. Hence, general strategies for manipulation of co-factor metabolism in industrially relevant hosts are of significance. Here, we demonstrate an improvement in α-ketoglutarate (AKG) production in S. cerevisiae using a novel approach based on synthetic rescue. Here, we first perturb the cytosolic NADPH metabolism via deletion of glucose-6-phosphate dehydrogenase (ZWF1). In parallel, we used a strain design algorithm to identify strategies for further improvement in AKG production. Implementation of the identified genetic targets, including disruption of succinyl-CoA Ligase (LSC2) and constitutive expression of NADP+-specific isocitrate dehydrogenases (IDP1 and IDP2) resulted in more than 3 fold improvement in AKG production as compared to the wild type. Our results demonstrate this improvement is due to a synthetic rescue mechanism in which the metabolic flux was redirected towards AKG production through the manipulation of redox cofactors. Disrupting lsc2 in zwf1 mutant improved specific growth rate more than 15% as compared to the zwf1 mutant. In addition, our result suggests that cytosolic isocitrate dehydrogenase (IDP2) may be regulated by isocitrate pools. Together, these results suggest the ability to improve metabolite production via a model guided synthetic rescue mechanism in S. cerevisiae and the potential for using IDP2 expression as a generalized strategy to effectively meet NADPH requirements in engineered strains.

This paper presents the results and lessons learned to improve the performance while drilling the 36-in tophole sections in the Culzean field field HPHT development. Seven 36-in sections were drilled in a batch sequence with less than four days between wells. This presented a challenge in quickly identifying operational and equipment changes necessary to improve performance in each subsequent well. The first well was drilled with no operational issues; however, the rate of penetration (ROP) was lower than had been expected for this area. Borehole inclination increased in the following two wells and required significant reaming to reduce the inclination observed. Damage was also observed to the 26-in × 36-in Hole Opener, suspected to be due to the additional reaming work. As the reaming impacted operational efficiency and equipment, a re-design of the bottomhole assembly (BHA) was initiated. To maintain verticality without the need to backream a 17.5-in Rotary Steerable System (RSS) was added between the 17.5-in Bit and the 26-in × 36-in staged Hole Opener on the fourth well. The RSS system was then used in this configuration for the remaining three wells, resulting in a 24% improvement in drilling performance over the baseline well.

// Aine G. O’Sullivan 1, * , Eamon P. Mulvaney 1, * , Paula B. Hyland 1 , B. Therese Kinsella 1 1 UCD School of Biomolecular and Biomedical Sciences, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland * These authors have contributed equally to this work Correspondence to: B. Therese Kinsella, e-mail: therese.kinsella@ucd.ie Keywords: thromboxane, receptor, cancer, prostate, protein kinase C-related kinase Received: May 01, 2015 Accepted: July 06, 2015 Published: July 20, 2015 ABSTRACT The prostanoid thromboxane (TX) A 2 is increasingly implicated in neoplastic progression, including prostate cancer (PCa). Mechanistically, we recently identified protein kinase C-related kinase (PRK) 1 as a functional interactant of both the TPα and TPβ isoforms of the human T prostanoid receptor (TP). The interaction with PRK1 was not only essential for TPα/TPβ-induced PCa cell migration but also enabled the TXA 2 -TP axis to induce phosphorylation of histone H3 at Thr11 (H3Thr11), an epigenetic marker both essential for and previously exclusively associated with androgen-induced chromatin remodelling and transcriptional activation. PRK1 is a member of a subfamily of three structurally related kinases comprising PRK1/PKNα, PRK2/PKNγ and PRK3/PKNβ that are widely yet differentially implicated in various cancers. Hence, focusing on the setting of prostate cancer, this study investigated whether TPα and/or TPβ might also complex with PRK2 and PRK3 to regulate their activity and neoplastic responses. While TPα and TPβ were found in immune complexes with PRK1, PRK2 and PRK3 to regulate their activation and signalling, they do so differentially and in a TP agonist-regulated manner dependent on the T-loop activation status of the PRKs but independent of their kinase activity. Furthermore, TXA 2 -mediated neoplastic responses in prostate adenocarcinoma PC-3 cells, including histone H3Thr11 phosphorylation, was found to occur through a PRK1- and PRK2-, but not PRK3-, dependent mechanism. Collectively, these data suggest that TXA 2 acts as both a neoplastic and epigenetic regulator and provides a mechanistic explanation, at least in part, for the prophylactic benefits of Aspirin in reducing the risk of certain cancers.

New reactor concepts to implement thorium-based fuel cycles have been explored to achieve maximum resource utilization. Pressure tube heavy water reactors (PT-HWRs) are highly advantageous for impl...

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.

Accurate and complete nuclear data are a fundamental requirement for any nuclear reactor model. Present nuclear data evaluations have been tested and validated against experiments that cover operating conditions and materials that are typical of conventional reactors (e.g. thermal light and heavy water moderated reactors, and some fast reactors). The Canadian supercritical water-cooled reactor (SCWR) is an advanced reactor concept for which, like all advanced GEN-IV reactor concepts, operating conditions and materials differ significantly from conventional reactors. Consequently, current nuclear data evaluations may not be suitable for modeling the Canadian SCWR, either due to assumptions or gaps in the evaluations or gaps in the experimental data on which the evaluations are based. In this paper, a simplified model of an SCWR fuel channel with fresh fuel is analyzed in order to determine the sensitivities and uncertainties of the model to nuclear data. The results are used to determine which isotopes and which reactions make the largest contributions to the sensitivity and uncertainties in key reactor physics parameters such as the neutron multiplication factor, k, and various lattice reactivity coefficients.

The use of lignocellulosic biomass is critical for the economic production of transportation fuels and chemicals in renewable bioprocesses. While biomass is an abundant resource, necessary pretreatment to yield fermentable monosaccharides produces toxic compounds that dramatically affect fermentation performance. Weak acids such as acetic acid play an important role in the toxicity of lignocellulosic hydrolysate to Saccharomyces cerevisiae, a commonly used industrial organism. In order to explore the ramifications of weak acid inhibition on cellular metabolism, we adapted a genome-scale metabolic model of S. cerevisiae to describe toxicity of acetic acid by a decoupling mechanism. We evaluated the performance of the model in predicting growth rates and ethanol production characteristics under aerobic and anaerobic cultivations. We found that the model was able to capture the decreased growth during aerobic cultivations in the presence of acetic acid, but was unable to capture the increase in etha...

Flattening filter free (FFF) linear accelerators allow for an increase in instantaneous dose-rate of the x-ray pulses by a factor of 2-6 over the conventional flattened output. As a result, radiobiological investigations are being carried out to determine the effect of these higher dose-rates on cell response. The studies reported thus far have presented conflicting results, highlighting the need for further investigation. To determine the radiobiological impact of the increased dose-rates from FFF exposures a Varian Truebeam medical linear accelerator was used to irradiate two human cancer cell lines in vitro, DU-145 prostate and H460 non-small cell lung, with both flattened and FFF 6 MV beams. The fluence profile of the FFF beam was modified using a custom-designed Nylon compensator to produce a similar dose profile to the flattened beam (6X) at the cell surface but at a higher instantaneous dose-rate. For both cell lines there appeared to be no significant change in cell survival. Curve fitting coefficients for DU145 cells irradiated with constant average dose-rates were 6X: α = 0.09 ± 0.03, β = 0.03 ± 0.01 and 6FFF: α = 0.14 ± 0.13, β = 0.03 ± 0.02 with a significance of p = 0.75. For H460 cells irradiated with the same instantaneous dose-rate but different average dose-rate the fit coefficients were 6FFF (low dose-rate): α = 0.21 ± 0.11, 0.07 ± 0.02 and 6FFF (high dose-rate): α = 0.21 ± 0.16, 0.07 ± 0.03, with p = 0.79. The results indicate that collective damage behaviour does not occur at the instantaneous dose-rates investigated here and that the use of either modality should result in the same clinical outcome, however this will require further validation in vivo.

Gold nanoparticle radiosensitization represents a novel technique in enhancement of ionising radiation dose and its effect on biological systems. Variation between theoretical predictions and experimental measurement is significant enough that the mechanism leading to an increase in cell killing and DNA damage is still not clear. We present the first experimental results that take into account both the measured biodistribution of gold nanoparticles at the cellular level and the range of the product electrons responsible for energy deposition. Combining synchrotron-generated monoenergetic X-rays, intracellular gold particle imaging and DNA damage assays, has enabled a DNA damage model to be generated that includes the production of intermediate electrons. We can therefore show for the first time good agreement between the prediction of biological outcomes from both the Local Effect Model and a DNA damage model with experimentally observed cell killing and DNA damage induction via the combination of X-rays and GNPs. However, the requirement of two distinct models as indicated by this mechanistic study, one for short-term DNA damage and another for cell survival, indicates that, at least for nanoparticle enhancement, it is not safe to equate the lethal lesions invoked in the local effect model with DNA damage events.

MATTHEW R. FIRST1*, EDWARD J. LEMIEUX2, WAYNE B. HYLAND3, JONATHAN F. GRANT4, CAMERON S. MOSER5, SCOTT C. RILEY1, STEPHANIE H. ROBBINS-WAMSLEY1, MIA K. STEINBERG6, TIMOTHY P. WIER5 AND LISA A. DRAKE7 1 SAIC, INC., KEY WEST, FL, USA, NAVAL RESEARCH LABORATORY, CODE 6130, WASHINGTON, DC, USA, AZIMUTH TECHNICAL CONSULTANTS, KEY WEST, FL, USA, BATTENKILL TECHNOLOGIES, MANCHESTER CENTER, VT, USA, EXCET, INC., KEY WEST, FL, USA, NAVAL RESEARCH LABORATORY, CODE 6136, WASHINGTON, DC, USA AND NAVAL RESEARCH LABORATORY, CODE 6136, KEY WEST, FL, USA

Gold nanopa rticles (GNPs) are of considerableinterest for use as a radiosensitizer, because of their biocompat-ibility and their ability to increase dose deposited because oftheir high mass energy absorption coefficient. Their sensitizingproperties have been verified experimentally, but a discrepancybetween the exper imental results and theoretical predictionssuggests that the sensitizing effect does not depend solely ongold’s superior absorption of energetic photons. Thi s workpresents the results of three sets of experiments that indepen-dently mapped out the energy dependence of the radiosensitiz-ing effects of GNPs on plasmid DNA suspended in water. Incident photon energy was varied from 11.8 to 80 keV through the use ofmonochromatic synchrotron and broadband X-rays. These results depart significantly from the theoretical predictions in two ways:First, the sensitization is signi ficantly larger than would be predicted; second, it does not vary with energy as would be predicted fromenergy absorption coefficients. These results clearly demonstra te that the effects of GNP-enhanced therapies cannot be predicted byconsidering additional dose alone and that a greater understanding of the processes involved is necessary for the development offuture therapeutics

Purpose Gold nanoparticles (GNPs) have been shown to cause sensitization with kilovoltage (kV) radiation. Differences in the absorption coefficient between gold and soft tissue, as a function of photon energy, predict that maximum enhancement should occur in the kilovoltage (kV) range, with almost no enhancement at megavoltage (MV) energies. Recent studies have shown that GNPs are not biologically inert, causing oxidative stress and even cell death, suggesting a possible biological mechanism for sensitization. The purpose of this study was to assess GNP radiosensitization at clinically relevant MV X-ray energies. Methods and Materials Cellular uptake, intracellular localization, and cytotoxicity of GNPs were assessed in normal L132, prostate cancer DU145, and breast cancer MDA-MB-231 cells. Radiosensitization was measured by clonogenic survival at kV and MV photon energies and MV electron energies. Intracellular DNA double-strand break (DSB) induction and DNA repair were determined and GNP chemosensitization was assessed using the radiomimetic agent bleomycin. Results GNP uptake occurred in all cell lines and was greatest in MDA-MB-231 cells with nanoparticles accumulating in cytoplasmic lysosomes. In MDA-MB-231 cells, radiation sensitizer enhancement ratios (SERs) of 1.41, 1.29, and 1.16 were achieved using 160 kVp, 6 MV, and 15 MV X-ray energies, respectively. No significant effect was observed in L132 or DU145 cells at kV or MV energies (SER 0.97–1.08). GNP exposure did not increase radiation-induced DSB formation or inhibit DNA repair; however, GNP chemosensitization was observed in MDA-MB-231 cells treated with bleomycin (SER 1.38). Conclusions We have demonstrated radiosensitization in MDA-MB-231 cells at MV X-ray energies. The sensitization was cell-specific with comparable effects at kV and MV energies, no increase in DSB formation, and GNP chemopotentiation with bleomycin, suggesting a possible biological mechanism of radiosensitization.

Efforts to develop a better diagnostic assay for bovine tuberculosis have shown that the sensitivity and specificity of an assay can be improved by the use of two or more antigens. As reported here, we developed a multiplex chemiluminescent immunoassay that can simultaneously detect antibody activity to 25 antigens in a single well in a 96-well plate array format. The chemiluminescent signal is captured with a digital imaging system and analyzed with a macro program that tracks each serum for its pattern of antibody activity for Mycobacterium bovis antigens. The comparison of sera from 522 infected and 1,489 uninfected animals showed that a sensitivity of 93.1% and a specificity of 98.4% can be achieved with a combination of antigens. The assay system is rapid and can be automated for use in a centralized laboratory.

A general technique that corrects γ -ray gated β decay-curve data for detector pulse pile-up is presented. The method includes corrections for non-zero time-resolution and energy-threshold effects in addition to a special treatment of saturating events due to cosmic rays. This technique is verified through a Monte Carlo simulation and experimental data using radioactive beams of Na 26 implanted at the center of the 8 π γ -ray spectrometer at the ISAC facility at TRIUMF in Vancouver, Canada. The β -decay half-life of Na 26 obtained from counting 1809-keV γ -ray photopeaks emitted by the daughter Mg 26 was determined to be T 1 / 2 = 1.07167 ± 0.00055 s following a 27 σ correction for detector pulse pile-up. This result is in excellent agreement with the result of a previous measurement that employed direct β counting and demonstrates the feasibility of high-precision β -decay half-life measurements through the use of high-purity germanium γ -ray detectors. The technique presented here, while motivated by superallowed-Fermi β decay studies, is general and can be used for all half-life determinations (e.g. α -, β -, X-ray, fission) in which a γ -ray photopeak is used to select the decays of a particular isotope.

Methods of optimizing the performance of an array of Compton-suppressed, segmented HPGe clover detectors have been developed which rely on the physical position sensitivity of both the HPGe crystals and the Compton-suppression shields. These relatively simple analysis procedures promise to improve the precision of experiments with the TRIUMF-ISAC Gamma-Ray Escape-Suppressed Spectrometer (TIGRESS). Suppression schemes will improve the efficiency and peak-to-total ratio of TIGRESS for high γ-ray multiplicity events by taking advantage of the 20-fold segmentation of the Compton-suppression shields, while the use of different summing schemes will improve results for a wide range of experimental conditions. The benefits of these methods are compared for many γ-ray energies and multiplicities using a GEANT4 simulation, and the optimal physical configuration of the TIGRESS array under each set of conditions is determined.

Tests of the performance of a 32-fold segmented HPGe clover detector coupled to a 20-fold segmented Compton-suppression shield, which form a prototype element of the TRIUMF-ISAC Gamma-Ray Escape-Suppressed Spectrometer (TIGRESS), have been made. Peak-to-total ratios and relative efficiencies have been measured for a variety of γ -ray energies. These measurements were used to validate a GEANT4 simulation of the TIGRESS detectors, which was then used to create a simulation of the full 12-detector array. Predictions of the expected performance of TIGRESS are presented. These predictions indicate that TIGRESS will be capable, for single 1 MeV γ rays, of absolute detection efficiencies of 17% and 9.4%, and peak-to-total ratios of 54% and 61% for the “high-efficiency” and “optimized peak-to-total” configurations of the array, respectively.

The TRIUMF-ISAC gamma-ray escape-suppressed spectrometer (TIGRESS) is a new γ-ray detector array being developed for use at TRIUMF's Isotope Separator and Accelerator (ISAC) radioactive ion beam facility. TIGRESS will comprise 12 32-fold segmented clover-type HPGe detectors coupled with 20-fold segmented modular Compton suppression shields and custom digital signal processing electronics. This paper provides an overview of the TIGRESS project and progress in its development to date.

A measurement of the half-life of 62Ga was made as part of a programme of high-precision superallowed Fermi β decay studies at the ISAC radioactive beam facility. The experiment was conducted by counting β+ particles from the decay of 62Ga in a 4π gas proportional counter. The half-life was measured to be 116.01 ± 0.19 ms. Several parameters were varied during the experiment to test for systematic effects, but no significant effects were found.

High-resolution γ-ray spectroscopy is essential to fully exploit the unique, high-quality beams available at the next generation of radioactive ion beam facilities such as the TRIUMF isotope separator and accelerator (ISAC). The 8π spectrometer, which consists of 20 Compton-suppressed HPGe detectors, has recently been reconfigured for a vigorous research programme in weak interaction and nuclear structure physics. With the addition of a variety of ancillary detectors it has become the world's most powerful device dedicated to β-decay studies. This paper provides a brief overview of the apparatus and highlights from recent experiments.

BaF 2 detectors for picosecond gamma-ray decay lifetime measurements have been installed into the 8π gamma-ray spectrometer as a proof-of-principle for a possible installation of a full array of ten detectors. Using four detectors a test measurement of the half-life of the 2 + state in 152 Sm resulted in a value of 1.33(6) ns, compared with a published value of 1.396 ns. Measurements with a 26 Na stopped beam were performed with various master-trigger conditions. Using a master trigger of germanium-SCEPTAR-BaF 2 OR BaF 2 -BaF 2 , the FWHM of the BaF 2 -BaF 2 triggered events was found to be ∼290 ps compared with ∼ 1.9 ns for the germanium-SCEPTAR-BaF 2 triggered events. Simulations using GEANT4 of a suggested BaF 2 lifetime measurement system have been carried out. These illustrate the considerable gain in spectrum quality which can be expected using simple add-back protocols.

The TRIUMF-ISAC Gamma-Ray Escape-Suppressed Spectrometer (TIGRESS) will consist of twelve units of four high-purity germanium (HPGe) crystals in a common cryostat. The outer contacts of each crystal will be divided into four quadrants and two lateral segments for a total of eight outer contacts. The performance of a prototype HPGe four-crystal unit has been investigated. Integrated noise spectra for all contacts were measured. Energy resolutions, relative efficiencies for both individual crystals and for the entire unit, and peak-to-total ratios were measured with point-like sources. Position-dependent performance was measured by moving a collimated source across the face of the detector.

Sensitivity to the locations of γ -ray interactions within a 32-fold segmented clover-type HPGe detector has been investigated through 90 ∘ Compton scattering of 661.6 keV γ -rays from a collimated Cs 137 source. A mean position sensitivity of 0.44 mm at an energy of 373 keV is deduced by comparing the average pulse shapes for net charge collecting signals, as well as transient induced signals in neighbouring contacts, from 1007 pairs of three-dimensionally localized interaction points. The reconstruction of individual event locations based on a χ 2 comparison with the measured set of basis waveforms is presented.

The properties of high-K isomers have been investigated by measuring γ rays from a source of the 31-year 178Hfm2 isomer and from the decay of implanted 178,179Lu beams. Low-intensity transitions have been identified in the decay of 178Hfm2, demonstrating a consistent extension of K-hindrance systematics to higher multipolarities, and elucidating the spin-dependence of the mixing between the two Kπ = 8- bands. A search is underway for new isomers in 178,179Lu and the preliminary results of the analysis are reported. © 2004 Elsevier B.V. All rights reserved.

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.

High-spin states in the N=Z nucleus 72Kr have been populated in the 40Ca(40Ca, 2α)72Kr fusion–evaporation reaction at a beam energy of 165 MeV and using a thin isotopically enriched 40Ca target. The experiment, performed at Argonne National Laboratory close to Chicago, USA, employed the Gammasphere array for γ-ray detection coupled to the Microball array for charged particle detection. The previously observed bands in 72Kr were extended to a higher excitation energy of ~24 MeV and higher angular momentum of 30. Using the Doppler-shift attenuation method, the lifetimes of high-spin states were measured for the first time in order to investigate deformation changes associated with the g9/2 proton and neutron alignments in this N=Z nucleus. An excellent agreement with theoretical calculations including only standard t=1 np pairing was observed.

CORRIGENDUM: Biological consequences of nanoscale energy deposition near irradiated heavy atom nanoparticles

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.

Use of lignocellulosic biomass as a second generation feedstock in the biofuels industry is a pressing challenge. Among other difficulties in using lignocellulosic biomass, one major challenge is the optimal utilization of both 6-carbon (glucose) and 5-carbon (xylose) sugars by industrial microorganisms. Most industrial microorganisms preferentially utilize glucose over xylose owing to the regulatory phenomenon of carbon catabolite repression (CCR). Microorganisms that can co-utilize glucose and xylose are of considerable interest to the biofuels industry due to their ability to simplify the fermentation processes. However, elimination of CCR in microorganisms is challenging due to the multiple coordinating mechanisms involved. We report a novel algorithm, SIMUP, which finds metabolic engineering strategies to force co-utilization of two sugars, without targeting the regulatory pathways of CCR. Mutants of Escherichia coli based on SIMUP algorithm showed predicted growth phenotypes and co-utilized glucose and xylose; however, consumed the sugars slower than the wild-type. Some solutions identified by the algorithm were based on stoichiometric imbalance and were not obvious from the metabolic network topology. Furthermore, sequencing studies on the genes involved in CCR showed that the mechanism for co-utilization of the sugars could be different from previously known mechanisms.

Background and purpose The addition of gold nanoparticles (GNPs) to tumours leads to an increase in dose due to their high density and energy absorption coefficient, making it a potential radiosensitiser. However, experiments have observed radiosensitisations significantly larger than the increase in dose alone, including at megavoltage energies where gold's relative energy absorption is lowest. This work investigates whether GNPs create dose inhomogeneities on a sub-cellular scale which combine with non-linear dose dependence of cell survival to be the source of radiosensitisation at megavoltage energies. Materials and methods Monte Carlo simulations were carried out to calculate dose in the vicinity of a single GNP on the nanoscale. The effect of this nanoscale dose distribution was then modelled for MDA-MB-231 cells exposed to 2nm GNPs, and compared to experimental results. Results Dramatic dose inhomogeneities occur around GNPs exposed to megavoltage radiation. When analysed using the Local Effect Model, these inhomogeneities lead to significant radiosensitisation, in agreement with experimental results. Conclusions This work suggests that GNP radiosensitisation is driven by inhomogeneities in dose on the nanoscale, rather than changes in dose over the entire cell, which may contribute to the similar radiosensitisation observed in megavoltage and kilovoltage experiments. The short range of these inhomogeneities and the variation in enhancement in different cells suggests sub-cellular localisation is important in determining GNP radiosensitisation.

Gold nanoparticles (GNPs) are being proposed as contrast agents to enhance X-ray imaging and radiotherapy, seeking to take advantage of the increased X-ray absorption of gold compared to soft tissue. However, there is a great discrepancy between physically predicted increases in X-ray energy deposition and experimentally observed increases in cell killing. In this work, we present the first calculations which take into account the structure of energy deposition in the nanoscale vicinity of GNPs and relate this to biological outcomes, and show for the first time good agreement with experimentally observed cell killing by the combination of X-rays and GNPs. These results are not only relevant to radiotherapy, but also have implications for applications of heavy atom nanoparticles in biological settings or where human exposure is possible because the localised energy deposition high-lighted by these results may cause complex DNA damage, leading to mutation and carcinogenesis.

The effect of a cold (

Two of the four known rotational bands in {sup 75}Rb were studied via the {sup 40}Ca({sup 40}Ca,{alpha}p){sup 75}Rb reaction at a beam energy of 165 MeV. Transitions were observed up to the maximum spin I{sub max} of the assigned configuration in one case and one-transition short of I{sub max} in the other. Lifetimes were determined using the residual Doppler shift attenuation method. The deduced transition quadrupole moments show a small decrease with increasing spin, but remain large at the highest spins. The results obtained are in good agreement with cranked Nilsson-Strutinsky calculations, which indicate that these rotational bands do not terminate, but remain collective at I{sub max}.

Cold atmospheric pressure plasmas offer a unique environment for treatments of soft materials, including bio-materials and living tissue. Single plasma devices can be as small as micro-meters allowing very precise treatments reducing damage to surrounding healthy living cells. It is essential to correlate direct plasma parameters with effects on bio-materials. There are various energy carrying species in the plasma such as charged particles, excited neutrals, radicals, and photons. In particular radical oxygen species ROS e.g. O, OH, have been identified as important.

AECL has developed enhanced versions of the reactor physics computer codes for analysis of CANDU® reactors and the ACR-1000™. The central codes that comprise the analysis toolset are WIMS-AECL (a lattice code), RFSP (a core code) and MCNP5 (a Monte Carlo code). The toolset, with ENDF/B-VI nuclear data, has been validated for application to the ACR-1000 design. In addition to comparisons of code predictions against relevant experiments conducted in AECL’s ZED-2 critical facility, advanced methods based on cross-section sensitivity/uncertainty (S/U) analysis were used to extend the results of bias and uncertainty in reactivity coefficients, derived from analysis of ZED-2 tests, to the ACR-1000 reactor. The validation of this toolset with ENDF/B-VII nuclear data is proposed for application to analysis of a Thorium-fuelled CANDU Reactor (TCR). The TCR is based on the Enhanced CANDU 6™ (EC6™) reactor [1] and would operate with a fuel design that incorporates both low-enriched uranium (LEU) oxide and thorium oxide fuel elements in the same fuel bundle to achieve enhanced fuel and core performance with thorium fuel. For the initial TCR toolset qualification, important reactor physics phenomena would be validated using several relevant ZED-2 experiments performed in the past. Results from experiments with a variety of oxide fuels are available, including plutonium/thorium (Pu/Th), 233 U/Th, 235 U/Th, LEU and CANDU-MOX (containing a mixture of plutonium, uranium and dysprosium to simulate the reactor physics affects of fuel burnup). Taken together along with other relevant experimental data, these experiments would be expected to address the important isotopes and many phenomena for the TCR and to enable the validation of the reactor physics toolset for this design. Additional confirmatory experiments would reduce uncertainties. This paper describes the qualification process, including validation, which is proposed to support the use of the reactor physics toolset for the TCR.Copyright © 2010 by ASME

With world stockpiles of used nuclear fuel increasing, the need to address the long-term utilization of this resource is being studied. Many of the transuranic (TRU) actinides in nuclear spent fuel produce decay heat for long durations, resulting in significant nuclear waste management challenges. These actinides can be transmuted to shorter-lived isotopes to reduce the decay heat period or consumed as fuel in a CANDU(R) reactor. Many of the design features of the CANDU reactor make it uniquely adaptable to actinide transmutation. The small, simple fuel bundle simplifies the fabrication and handling of active fuels. Online refuelling allows precise management of core reactivity and separate insertion of the actinides and fuel bundles into the core. The high neutron economy of the CANDU reactor results in high TRU destruction to fissile-loading ratio. This paper provides a summary of actinide transmutation schemes that have been studied in CANDU reactors at AECL, including the works performed in the past ( Boczar et al., 1996 , Chan et al., 1997 , Hyland and Dyck, 2007 , Hyland et al., 2009 ). The schemes studied include homogeneous scenarios in which actinides are uniformly distributed in all fuel bundles in the reactor, as well as heterogeneous scenarios in which dedicated channels in the reactor are loaded with actinide targets and the rest of the reactor is loaded with fuel. The transmutation schemes that are presented reflect several different partitioning schemes. Separation of americium, often with curium, from the other actinides enables targeted destruction of americium, which is a main contributor to the decay heat 100–1000 years after discharge from the reactor. Another scheme is group-extracted transuranic elements, in which all of the transuranic elements, plutonium (Pu), neptunium (Np), americium (Am), and curium (Cm) are extracted together and then transmuted. This paper also addresses ways of utilizing the recycled uranium, another stream from the separation of spent nuclear fuel, in order to drive the transmutation of other actinides.

The CANDU® reactor is the most resource-efficient reactor commercially available. The features that enable the CANDU reactor to utilize natural uranium facilitate the use of a wide variety of thorium fuel cycles. In the short term, the initial fissile material would be provided in a “mixed bundle”, in which low-enriched uranium (LEU) would comprise the outer two rings of a CANFLEX® bundle, with ThO2 in the central 8 elements. This cycle is economical, both in terms of fuel utilization and fuel cycle costs. The medium term strategy would be defined by the availability of plutonium and recovered uranium from reprocessed used LWR fuel. The plutonium could be used in Pu/Th bundles in the CANDU reactor, further increasing the energy derived from the thorium. Recovered uranium could also be effectively utilized in CANDU reactors. In the long term, the full energy potential from thorium could be realized through the recycle of the U-233 (and thorium) in the used CANDU fuel. Plutonium would only be required to top up the fissile content to achieve the desired burnup. Further improvements to the CANDU neutron economy could make possible a very close approach to the Self-Sufficient Equilibrium Thorium (SSET) cycle with a conversion ratio of unity, which would be completely self-sufficient in fissile material (recycled U-233).Copyright © 2010 by ASME

AUVs have proved robustness and high performance in applications including naval mine counter measures, marine research and deep water offshore oil and gas surveys. A next step is to introduce AUVs to under ice geophysical surveys. A main challenge for regular under ice operations is to handle the risk of a loss of a vehicle, or long operational interruptions. The paper discusses how to reduce this risk by careful tailoring of critical AUV subsystems. A fundamental requirement is to apply a robust, well designed and well proven vehicle, continually upgraded from field experiences. Another main challenge is to design a sensor suite that allows for cost efficient and fast mapping of the vast areas under ice. A geophysical sensor suite is presented and solutions for high area coverage rates examined.

A high-precision branching ratio measurement for the superallowed ${\ensuremath{\beta}}^{+}$ decay of $^{62}\mathrm{Ga}$ was performed at the Isotope Separator and Accelerator (ISAC) radioactive ion beam facility. The 8\ensuremath{\pi} spectrometer, an array of 20 high-purity germanium detectors, was employed to detect the \ensuremath{\gamma} rays emitted following Gamow-Teller and nonanalog Fermi ${\ensuremath{\beta}}^{+}$ decays of $^{62}\mathrm{Ga}$, and the SCEPTAR plastic scintillator array was used to detect the emitted \ensuremath{\beta} particles. Thirty \ensuremath{\gamma} rays were identified following $^{62}\mathrm{Ga}$ decay, establishing the superallowed branching ratio to be $99.858(8)%$. Combined with the world-average half-life and a recent high-precision $Q$-value measurement for $^{62}\mathrm{Ga}$, this branching ratio yields an $\mathit{ft}$ value of $3074.3\ifmmode\pm\else\textpm\fi{}1.1$ s, making $^{62}\mathrm{Ga}$ among the most precisely determined superallowed $\mathit{ft}$ values. Comparison between the superallowed $\mathit{ft}$ value determined in this work and the world-average corrected $\overline{\mathcal{F}t}$ value allows the large nuclear-structure-dependent correction for $^{62}\mathrm{Ga}$ decay to be experimentally determined from the CVC hypothesis to better than 7$%$ of its own value, the most precise experimental determination for any superallowed emitter. These results provide a benchmark for the refinement of the theoretical description of isospin-symmetry breaking in $A\ensuremath{\geqslant}62$ superallowed decays.

The nucleus Kr-74 has been populated in the Ca-40(Ca-40,2p alpha)Kr-74 fusion-evaporation reaction at a beam energy of 165 MeV and studied using the Gammasphere and Microball multidetector arrays. The lifetimes for low-spin states in the ground-state and two signature-split negative-parity bands were determined using the Doppler-shift attenuation method. These results are discussed together with the lifetimes measured for the high-spin states of these bands and compared with theoretical calculations.

The half-life of the superallowed {beta}{sup +} emitter {sup 62}Ga has been measured at TRIUMF's Isotope Separator and Accelerator facility using a fast-tape-transport system and 4{pi} continuous-flow gas proportional counter to detect the positrons from the decay of {sup 62}Ga to the daughter {sup 62}Zn. The result, T{sub 1/2}=116.100{+-}0.025 ms, represents the most precise measurement to date (0.022%) for any superallowed {beta}-decay half-life. When combined with six previous measurements of the {sup 62}Ga half-life, a new world average of T{sub 1/2}=116.121{+-}0.021 ms is obtained. This new half-life measurement results in a 20% improvement in the precision of the {sup 62}Ga superallowed ft value while reducing its mean by 0.9{sigma} to ft=3074.3(12) s. The impact of this half-life measurement on precision tests of the CVC hypothesis and isospin symmetry breaking corrections for A{>=}62 superallowed decays is discussed.

High-spin states in the N=Z nucleus {sup 72}Kr have been populated in the {sup 40}Ca({sup 40}Ca, 2{alpha}){sup 72}Kr fusion-evaporation reaction at a beam energy of 165 MeV using the Gammasphere array for {gamma}-ray detection coupled to the Microball array for charged particle detection. The previously observed bands in {sup 72}Kr were extended to an excitation energy of {approx}24 MeV and angular momentum of 30({Dirac_h}/2{pi}). Using the Doppler shift attenuation method the lifetimes of high-spin states were measured for the first time. Excellent agreement between the results of calculations within the isovector mean field theory and experiment is observed both for rotational and deformation properties. No enhancement of quadrupole deformation expected in the presence of isoscalar t=0 np pairing is observed. Current data do not show any evidence for the existence of the isoscalar np pairing.

The \ensuremath{\beta}-decay of $^{32}\mathrm{Na}$ has been studied using $\ensuremath{\beta}\text{\ensuremath{-}}\ensuremath{\gamma}$ coincidences. New transitions and levels are tentatively placed in the level scheme of $^{32}\mathrm{Mg}$ from an analysis of $\ensuremath{\gamma}\text{\ensuremath{-}}\ensuremath{\gamma}$ and $\ensuremath{\beta}\text{\ensuremath{-}}\ensuremath{\gamma}\text{\ensuremath{-}}\ensuremath{\gamma}$ coincidences. The observation of the indirect feeding of the 2321 keV state in $^{32}\mathrm{Mg}$ removes some restrictions previously placed on the spin assignment for this state. No evidence of a state at 2117 keV in $^{32}\mathrm{Mg}$ is found. Previously unobserved weak transitions up to 5.4 MeV were recorded but could not be placed in the decay scheme of $^{32}\mathrm{Na}$.