Identification of a very long chain polyunsaturated fatty acid Δ4-desaturase from the microalga Pavlova lutheri11The sequence reported in this paper has been submitted to GenBank database under the accession number AY332747.

AbstractPavlova lutheri, a marine microalga, is rich in the very long chain polyunsaturated fatty acids (VLCPUFAs) eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Using an expressed sequence tag approach, we isolated a cDNA designated Pldes1, and encoding an amino acid sequence showing high similarity with polyunsaturated fatty acid front-end desaturases. Heterologous expression in yeast demonstrated that PlDES1 desaturated 22:5n-3 and 22:4n-6 into 22:6n-3 and 22:5n-6 respectively, and was equally active on both substrates. Thus, PlDES1 is a novel VLCPUFA Δ4-desaturase. Pldes1 expression is four-fold higher during the mid-exponential phase of growth compared to late exponential and stationary phases

Quantisation of Hopping Magnetoresistance Prefactor in Strongly Correlated Two-Dimensional Electron Systems

We report an universal behaviour of hopping transport in strongly interacting mesoscopic two-dimensional electron systems (2DES). In a certain window of background disorder, the resistivity at low perpendicular magnetic fields follows the expected relation $\rho(B_\perp) = \rho_{\rm{B}}\exp(\alpha B_\perp^2)$. The prefactor $\rho_{\rm{B}}$ decreases exponentially with increasing electron density but saturates to a finite value at higher densities. Strikingly, this value is found to be universal when expressed in terms of absolute resistance and and shows quantisation at $R_{\rm{B}}\approx h/e^2$ and $R_{\rm{B}}\approx 1/2$ $h/e^2$. We suggest a strongly correlated electronic phase as a possible explanation.Comment: 5 pages, 3 figures, Proceedings of EP2DS 17, Reference adde

Evolution since z = 0.5 of the Morphology-Density relation for Clusters of Galaxies

Using traditional morphological classifications of galaxies in 10 intermediate-redshift (z~0.5) clusters observed with WFPC-2 on the Hubble Space Telescope, we derive relations between morphology and local galaxy density similar to that found by Dressler for low-redshift clusters. Taken collectively, the `morphology-density' relationship, M-D, for these more distant, presumably younger clusters is qualitatively similar to that found for the local sample, but a detailed comparison shows two substantial differences: (1) For the clusters in our sample, the M-D relation is strong in centrally concentrated ``regular'' clusters, those with a strong correlation of radius and surface density, but nearly absent for clusters that are less concentrated and irregular, in contrast to the situation for low redshift clusters where a strong relation has been found for both. (2) In every cluster the fraction of elliptical galaxies is as large or larger than in low-redshift clusters, but the S0 fraction is 2-3 times smaller, with a proportional increase of the spiral fraction. Straightforward, though probably not unique, interpretations of these observations are (1) morphological segregation proceeds hierarchically, affecting richer, denser groups of galaxies earlier, and (2) the formation of elliptical galaxies predates the formation of rich clusters, and occurs instead in the loose-group phase or even earlier, but S0's are generated in large numbers only after cluster virialization.Comment: 35 pages, 19 figures, uses psfig. Accepted for publication in Ap

Use of methods for specifying the target difference in randomised controlled trial sample size calculations : Two surveys of trialists' practice

© The Author(s), 2014.Peer reviewedPublisher PD

Shale prospectivity onshore Britain

The UK Department of Energy and Climate Change (DECC) commissioned the British Geological Survey (BGS) to summarize the available geological knowledge, integrate new seismic mapping and well analysis, and make preliminary in-place resource assessments for the three most prospective areas onshore Britain to foster a greater understanding of the unconventional shale resource potential in advance of the 14th Landward Licensing Round. The first study, published in June 2013, reviewed the Carboniferous Bowland–Hodder shales across central Britain where a large volume of in-place gas was assessed to be present. The second study, of the Jurassic shale of the Weald Basin in southern England, published in May 2014, concluded that owing to insufficient burial there was no significant Jurassic shale gas potential, but there could still be shale oil resources at several levels in the centre of the basin. The third study, published in June 2014, covered the Midland Valley of Scotland where both oil and gas potential in Carboniferous shales was identified. A large volume of in-place gas and oil resource has been assessed to be present. However, not enough is known at the time of writing to estimate a recovery factor or to estimate potential producible reserves. This paper summarizes the results of the BGS reports and their impact on the subsequent licensing process in England

175 GHz, 400-fs-pulse harmonically mode-locked surface emitting semiconductor laser

We report a harmonically mode-locked vertical external cavity surface emitting laser (VECSEL) producing 400 fs pulses at a repetition frequency of 175 GHz with an average output power of 300 mW. Harmonic mode-locking was established using a 300 µm thick intracavity single crystal diamond heat spreader in thermal contact with the front surface of the gain sample using liquid capillary bonding. The repetition frequency was set by the diamond microcavity and stable harmonic mode locking was achieved when the laser cavity length was tuned so that the laser operated on the 117th harmonic of the fundamental cavity. When an etalon placed intracavity next to the gain sample, but not in thermal contact was used pulse groups were observed. These contained 300 fs pulses with a spacing of 5.9 ps. We conclude that to achieve stable harmonic mode locking at repetition frequencies in the 100s of GHz range in a VECSEL there is a threshold pulse energy above which harmonic mode locking is achieved and below which groups of pulses are observed

Designing personalised cancer treatments

The concept of personalised medicine for cancer is not new. It arguably began with the attempts by Salmon and Hamburger to produce a viable cellular chemosensitivity assay in the 1970s, and continues to this day. While clonogenic assays soon fell out of favour due to their high failure rate, other cellular assays fared better and although they have not entered widespread clinical practice, they have proved to be very useful research tools. For instance, the ATP-based chemosensitivity assay was developed in the early 1990s and is highly standardised. It has proved useful for evaluating new drugs and combinations, and in recent years has been used to understand the molecular basis of drug resistance and sensitivity to anti-cancer drugs. Recent developments allow unparalleled genotyping and phenotyping of tumours, providing a plethora of targets for the development of new cancer treatments. However, validation of such targets and new agents to permit translation to the clinic remains difficult. There has been one major disappointment in that cell lines, though useful, do not often reflect the behaviour of their parent cancers with sufficient fidelity to be useful. Low passage cell lines — either in culture or xenografts are being used to overcome some of these issues, but have several problems of their own. Primary cell culture remains useful, but large tumours are likely to receive neo-adjuvant treatment before removal and that limits the tumour types that can be studied. The development of new treatments remains difficult and prediction of the clinical efficacy of new treatments from pre-clinical data is as hard as ever. One lesson has certainly been that one cannot buck the biology — and that understanding the genome alone is not sufficient to guarantee success. Nowhere has this been more evident than in the development of EGFR inhibitors. Despite overexpression of EGFR by many tumour types, only those with activating EGFR mutations and an inability to circumvent EGFR blockade have proved susceptible to treatment. The challenge is how to use advanced molecular understanding with limited cellular assay information to improve both drug development and the design of companion diagnostics to guide their use. This has the capacity to remove much of the guesswork from the process and should improve success rates

Designing personalised cancer treatments

The concept of personalised medicine for cancer is not new. It arguably began with the attempts by Salmon and Hamburger to produce a viable cellular chemosensitivity assay in the 1970s, and continues to this day. While clonogenic assays soon fell out of favour due to their high failure rate, other cellular assays fared better and although they have not entered widespread clinical practice, they have proved to be very useful research tools. For instance, the ATP-based chemosensitivity assay was developed in the early 1990s and is highly standardised. It has proved useful for evaluating new drugs and combinations, and in recent years has been used to understand the molecular basis of drug resistance and sensitivity to anti-cancer drugs. Recent developments allow unparalleled genotyping and phenotyping of tumours, providing a plethora of targets for the development of new cancer treatments. However, validation of such targets and new agents to permit translation to the clinic remains difficult. There has been one major disappointment in that cell lines, though useful, do not often reflect the behaviour of their parent cancers with sufficient fidelity to be useful. Low passage cell lines — either in culture or xenografts are being used to overcome some of these issues, but have several problems of their own. Primary cell culture remains useful, but large tumours are likely to receive neo-adjuvant treatment before removal and that limits the tumour types that can be studied. The development of new treatments remains difficult and prediction of the clinical efficacy of new treatments from pre-clinical data is as hard as ever. One lesson has certainly been that one cannot buck the biology — and that understanding the genome alone is not sufficient to guarantee success. Nowhere has this been more evident than in the development of EGFR inhibitors. Despite overexpression of EGFR by many tumour types, only those with activating EGFR mutations and an inability to circumvent EGFR blockade have proved susceptible to treatment. The challenge is how to use advanced molecular understanding with limited cellular assay information to improve both drug development and the design of companion diagnostics to guide their use. This has the capacity to remove much of the guesswork from the process and should improve success rates

What do older people do when sitting and why? Implications for decreasing sedentary behaviour

Background and Objectives: Sitting less can reduce older adults’ risk of ill health and disability. Effective sedentary behavior interventions require greater understanding of what older adults do when sitting (and not sitting), and why. This study compares the types, context, and role of sitting activities in the daily lives of older men and women who sit more or less than average. Research Design and Methods: Semistructured interviews with 44 older men and women of different ages, socioeconomic status, and objectively measured sedentary behavior were analyzed using social practice theory to explore the multifactorial, inter-relational influences on their sedentary behavior. Thematic frameworks facilitated between-group comparisons. Results: Older adults described many different leisure time, household, transport, and occupational sitting and non-sitting activities. Leisure-time sitting in the home (e.g., watching TV) was most common, but many non-sitting activities, including “pottering” doing household chores, also took place at home. Other people and access to leisure facilities were associated with lower sedentary behavior. The distinction between being busy/not busy was more important to most participants than sitting/not sitting, and informed their judgments about high-value “purposeful” (social, cognitively active, restorative) sitting and low-value “passive” sitting. Declining physical function contributed to temporal sitting patterns that did not vary much from day-to-day. Discussion and Implications: Sitting is associated with cognitive, social, and/or restorative benefits, embedded within older adults’ daily routines, and therefore difficult to change. Useful strategies include supporting older adults to engage with other people and local facilities outside the home, and break up periods of passive sitting at home