Translational arrest due to cytoplasmic redox stress delays adaptation to growth on methanol and heterologous protein expression in a typical fed-batch culture of Pichia pastoris

Results We have followed a typical fed-batch induction regime for heterologous protein production under the control of the AOX1 promoter using both microarray and metabolomic analysis. The genetic constructs involved 1 and 3 copies of the TRY1 gene, encoding human trypsinogen. In small-scale laboratory cultures, expression of the 3 copy-number construct induced the unfolded protein response (UPR) sufficiently that titres of extracellular trypsinogen were lower in the 3-copy construct than with the 1-copy construct. In the fed-batch-culture, a similar pattern was observed, with higher expression from the 1-copy construct, but in this case there was no significant induction of UPR with the 3-copy strain. Analysis of the microarray and metabolomic information indicates that the 3-copy strain was undergoing cytoplasmic redox stress at the point of induction with methanol. In this Crabtree-negative yeast, this redox stress appeared to delay the adaptation to growth on methanol and supressed heterologous protein production, probably due to a block in translation. Conclusion Although redox imbalance as a result of artificially imposed hypoxia has previously been described, this is the first time that it has been characterised as a result of a transient metabolic imbalance and shown to involve a stress response which can lead to translational arrest. Without detailed analysis of the underlying processes it could easily have been mis-interpreted as secretion stress, transmitted through the UPR

Assimilative real-time models of HF absorption at high latitudes

Improved real-time HF communications frequency management is required for aircraft on trans-polar routes. Polar cap absorption (PCA) models have therefore been adapted to assimilate real-time measurements of zenithal cosmic radio noise absorption (~ 30 MHz) from a large network of online riometers in Canada and Finland. Two types of PCA model have been developed and improvements to model accuracy following optimisation are quantified. Real-time optimisation is performed by age-weighting riometer measurements in a non-linear regression. This reduces root-mean-square errors (RMSE) from 2-3 dB to less than 1 dB and mean errors to within ±0.2 dB over a wide latitude range. This paper extends previous work by further optimising the models’ dependences on solar-zenith angle to account for differences in the ionospheric response at sunrise and sunset (the Twilight Anomaly). Two models of the rigidity cutoff latitudes are compared and one is optimised in real time by regression to riometer measurements. Whilst measurements from the NASA POES satellites may provide a direct measurement of the rigidity cut-off, it is observed that proton flux measurements from POES often need correcting for relativistic electron contamination for several hours at the start of a PCA event. An optimised real-time absorption model will be integrated into HF ray-tracing propagation predictions relating to measurements of HF signal strengths on a network of HF transmitters and receivers in the high northern latitudes

Electromagnetic navigation in total knee arthroplasty—a single center, randomized, single-blind study comparing the results with conventional techniques

We report on the results of a randomized study (n = 200) to compare total knee arthroplasty performed using conventional instrumentation or electromagnetic computer assisted surgical technique. 92% of navigated and 85% of conventional knees were implanted within ± 3° from neutral mechanical alignment; there was no statistically significant difference between these proportions. There was also no difference in femoral or tibial rotation assessed by CT scan. At 1 year follow up there was no statistical difference between the two groups in American Knee Society Score, Oxford Knee Scores, patient satisfaction, quality of life, hospital length of stay, complication rates or other adverse events. Tourniquet time in the navigated group was longer. Proving value for navigation in total knee arthroplasty surgery remains a challenge

Harnessing Erebus volcano's thermal energy to power year-round monitoring

Year-round monitoring of Erebus volcano (Ross Island) has proved challenging due to the difficulties of maintaining continuous power for scientific instruments, especially through the Antarctic winter. We sought a potential solution involving the harvesting of thermal energy dissipated close to the summit crater of the volcano in a zone of diffuse hot gas emissions. We designed, constructed and tested a power generator based on the Seebeck effect, converting thermal energy to electrical power, which could, in principle, be used to run monitoring devices year round. We report here on the design of the generator and the results of an 11 day trial deployment on Erebus volcano in December 2014. The generator produced a mean output power of 270 mW, although we identified some technical issues that had impaired its efficiency. Nevertheless, this is already sufficient power for some monitoring equipment and, with design improvements, such a generator could provide a viable solution to powering a larger suite of instrumentation

Fundamental performance similarities between individual pitch control strategies for wind turbines.

The use of blade individual pitch control (IPC) offers a means of reducing the harmful turbine structural loads that arise from the uneven and unsteady forcing from the oncoming wind. In recent years two different and competing IPC techniques have emerged that are characterised by the specific loads that they are primarily designed to attenuate. In the first instance, methodologies such as single-blade control and Clarke Transform-based control have been developed to reduce the unsteady loads on the rotating blades, whilst tilt-yaw control and its many variants instead target load reductions in the non rotating turbine structures, such as the tower and main bearing. Given the seeming disparities between these controllers, the aim of this paper is to show the fundamental performance similarities that exist between them and hence unify research in this area. Specifically, we show that single-blade controllers are equivalent to a particular class of tilt-yaw controller, which itself is equivalent to Clarke~Transform-based control. This means that three architecturally dissimilar IPC controllers exist that yield exactly the same performance in terms of load reductions on fixed and rotating turbine structures. We further demonstrate this outcome by presenting results obtained from high-fidelity closed-loop turbine simulations

Robotic arm-assisted bi-unicompartmental knee arthroplasty maintains natural knee joint anatomy compared with total knee arthroplasty : a prospective randomized controlled trial

Aims The aim of this study was to compare robotic arm-assisted bi-unicompartmental knee arthroplasty (bi-UKA) with conventional mechanically aligned total knee arthroplasty (TKA) in order to determine the changes in the anatomy of the knee and alignment of the lower limb following surgery. Methods An analysis of 38 patients who underwent TKA and 32 who underwent bi-UKA was performed as a secondary study from a prospective, single-centre, randomized controlled trial. CT imaging was used to measure coronal, sagittal, and axial alignment of the knee preoperatively and at three months postoperatively to determine changes in anatomy that had occurred as a result of the surgery. The hip-knee-ankle angle (HKAA) was also measured to identify any differences between the two groups. Results The pre- to postoperative changes in joint anatomy were significantly less in patients undergoing bi-UKA in all three planes in both the femur and tibia, except for femoral sagittal component orientation in which there was no difference. Overall, for the six parameters of alignment (three femoral and three tibial), 47% of bi-UKAs and 24% TKAs had a change of < 2° (p = 0.045). The change in HKAA towards neutral in varus and valgus knees was significantly less in patients undergoing bi-UKA compared with those undergoing TKA (p < 0.001). Alignment was neutral in those undergoing TKA (mean 179.5° (SD 3.2°)) while those undergoing bi-UKA had mild residual varus or valgus alignment (mean 177.8° (SD 3.4°)) (p < 0.001). Conclusion Robotic-assisted, cruciate-sparing bi-UKA maintains the natural anatomy of the knee in the coronal, sagittal, and axial planes better, and may therefore preserve normal joint kinematics, compared with a mechanically aligned TKA. This includes preservation of coronal joint line obliquity. HKAA alignment was corrected towards neutral significantly less in patients undergoing bi-UKA, which may represent restoration of the pre-disease constitutional alignment (p < 0.001)

The Fornax Spectroscopic Survey: The Number of Unresolved Compact Galaxies

We describe a sample of thirteen bright (18.5<Bj<20.1) compact galaxies at low redshift (0.05<z<0.21) behind the Fornax Cluster. These galaxies are unresolved on UK Schmidt sky survey plates, so would be missing from most galaxy catalogs compiled from this material. The objects were found during initial observations of The Fornax Spectroscopic Survey. This project is using the Two-degree Field spectrograph on the Anglo-Australian Telescope to obtain spectra for a complete sample of all 14000 objects, stellar and non-stellar, with 16.5<Bj<19.7, in a 12 square degree area centered on the Fornax cluster of galaxies. The surface density of compact galaxies with magnitudes 16.5<Bj<19.7 is 7+/-3 /sq.deg., representing 2.8+/-1.6% of all local (z<0.2) galaxies to this limit. There are 12+/-3 /sq.deg. with 16.5<Bj<20.2. They are luminous (-21.5<Mb<-18.0, for H0=50 km/s/mpc) and most have strong emission lines (H alpha equivalent widths of 40-200 A) and small sizes typical of luminous HII galaxies and compact narrow emission line galaxies. Four out of thirteen have red colors and early-type spectra, so are unlikely to have been detected in any previous surveys.Comment: LaTeX source; 5 pages including 3 figures; uses emulateapj.st

Assessing the applicability of terrestrial laser scanning for mapping englacial conduits

his is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike licence (http://creativecommons.org/licenses/by-nc-sa/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the same Creative Commons licence is included and the original work is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use.The morphology of englacial drainage networks and their temporal evolution are poorly characterised, particularly within cold ice masses. At present, direct observations of englacial channels are restricted in both spatial and temporal resolution. Through novel use of a terrestrial laser scanning (TLS) system, the interior geometry of an englacial channel in Austre Brøggerbreen, Svalbard, was reconstructed and mapped. Twenty-eight laser scan surveys were conducted in March 2016, capturing the glacier surface around a moulin entrance and the uppermost 122 m reach of the adjoining conduit. The resulting point clouds provide detailed 3-D visualisation of the channel with point accuracy of 6.54 mm, despite low (<60%) overall laser returns as a result of the physical and optical properties of the clean ice, snow, hoar frost and sediment surfaces forming the conduit interior. These point clouds are used to map the conduit morphology, enabling extraction of millimetre-to-centimetre scale geometric measurements. The conduit meanders at a depth of 48 m, with a sinuosity of 2.7, exhibiting teardrop shaped cross-section morphology. This improvement upon traditional surveying techniques demonstrates the potential of TLS as an investigative tool to elucidate the nature of glacier hydrological networks, through reconstruction of channel geometry and wall composition.Peer reviewedFinal Published versio