bluuebunny/crossref_metadata_2025 huggingface dataset:
TRAP INTEGRITY IN THE LAM IN ARIA HIGH-NANCAR TROUGH REGION,TIMOR SEA: PREDICTION OF FAULT SEAL FAILURE USING WELL-CONSTRAINED STRESS TENSORS AND FAULT SURFACES INTERPRETED FROM 3D SEISMIC
Authors: Castillo D.A. , Bishop D.J. , Donaldson I. , Kuek D. , Ruig M. de , Trupp M. , Shuster M.W.
Published: August 2017

Drilling in the Laminaria High and Nancar Trough areas has shown that many hydrocarbon traps are underfilled or completely breached. Previous studies have shown that fault-trap integrity is strongly influenced by the state of stress resolved on the reservoir bounding faults, suggesting that careful construction of a geomechanical model may reduce the risk of encountering breached reservoirs in exploration and appraisal wells. The ability of a fault to behave as a seal and support a hydrocarbon column is influenced in part by the principal stress directions and magnitudes, and fault geometry (dip and dip azimuth). If a fault is critically stressed with respect to the present-day stress field, there is a high likelihood that the fault will slip, thereby elevating fault zone permeability that enables hydrocarbons to leak. Leakage could be intermittent depending on the degree and rate of fracture healing, and on the recurrence rate between reactivated slip events.High-resolution wellbore images from over 15 wells have been analysed to construct a well-constrained stress tensor. Constraints are based on geomechanical parameters, along with drilling conditions that are consistent with the style of drilling-induced compressive and tensile wellbore wall failure seen in each of these wells. This regional stress analysis of permits AC/P8, AC/P16 and surrounding areas indicates a non-uniform strike-slip stress regime (SHmax > Sv > Shmin) with the orientation of the maximum principal horizontal stress (SHmax) varying systematically from north to south, similar to that previously reported for the western reaches of ZOCA. On the Laminaria High (AC/P8 and AC/L5), SHmax is 15°N ± 6°. Just south of the Laminaria High, there is a marked transition in the SHmax stress direction to about 63°N ± 6°. Over the Nancar Trough (AC/P16), the orientation is consistently NE-SW.Fault surfaces interpreted from 3D seismic data have been subdivided into discrete segments for the purpose of calculating the shear and normal stresses in order to resolve the Coulomb Failure Function (CFF) on each fault segment. The results have been displayed using 3D visualisation techniques to facilitate interpretation. The magnitude of hydrocarbon accumulation (column height) and leakage (residual column) deduced from well results may be explained in part by the CFF resolved on their respective reservoir-bounding faults. By integrating these stress determination and fault imaging technologies, explorationists and reservoir engineers will gain the ability to use these predictive tools to help quantify the likelihood of encountering a breached reservoir prior to drilling.
A STATE-OF-THE-ART REVIEW OF NEURAL NETWORKS FOR PERMEABILITY PREDICTION
Authors: Bruce A.G. , Wong P.M. , Zhang Y. , Salisch H.A. , Fung C.C. , Gedeon T.D.
Published: August 2017

This paper reviews the state-of-the-art of neural networks for permeability prediction from well logs. Good prediction of permeability is necessary for reservoir characterisation and is important for improving the reliability of the asset value of oil and gas companies. Two particular models, known as backpropagation and radial basis function networks, have been applied. From previous work, six innovative aspects are identified:choice of inputs;outlier detection and removal;data splitting;scaling;multiple networks; andprediction confidence.We have also provided a list of future research directions in the area, reflecting the current deficiencies of the use of neural networks. The topics are:the quality and quantity of core data;the maximum use of the logs;the compatibility of scales;the use of soft computing; andthe management of prediction confidence.The current applications are certainly the beginning of a new era. It is important for petrophysicists to take advantage of the advanced technologies.
APPLICATIONS OF MODERN AND ANCIENT GEOLOGICAL ANALOGUES IN CHARACTERISATION OF FLUVIAL AND FLUVIAL-LACUSTRINE DELTAIC RESERVOIRS IN THE COOPER BASIN
Authors: Lang S.C. , Kassan J. , Benson J.M. , Grasso C.A. , Avenell L.C.
Published: August 2017

Reservoir characterisation in fluvial and fluvial- lacustrine delta successions is enhanced by the use of appropriate modern and ancient analogues to understand subsurface reservoir architecture and to help build appropriately scaled reservoir models. Two case studies of reservoir characterisation in the Cooper Basin are used to illustrate the value of analogues. Firstly the Late Permian Toolachee Formation crevasse splay reservoirs of the Cooper Basin, southwest Queensland are outlined, and analogues from the Ob River in Western Siberia illustrate the relative scale of crevasse splay deposits within avulsion belts in a cool-temperate peat-forming environment. The South Blackwater coal mine in the Permian Bowen Basin is used as an analogue to quantify the 3D geometry and reservoir architecture of crevasse splays and to highlight subsurface reservoir heterogeneity.Secondly, the Early Permian Epsilon Formation shallow water lacustrine delta reservoirs are outlined, and analogues from the extant geometry of the distributary channels and relict mouth bar deposits from the fluvial dominated Neales Delta in Lake Eyre are used to interpret flow rate decline trends and probable reservoir architecture. The subsurface Tertiary lacustrine deltaic complex of the Sirikit Field from the Phitsanulok Basin, central Thailand, is selected as an ancient analogue for the multistorey reservoirs developed within amalgamated mouth bar complexes intersected in the lower Epsilon Formation.
AWAKENING OF A SLEEPING GIANT: SUNRISE- TROUBADOUR GAS-CONDENSATE FIELD
Authors: Seggie R.J. , Ainsworth R.B. , D.A.Johnson  , Koninx J.P.M. , Spaargaren B. , Stephenson P.M.
Published: August 2017

The Sunrise and Troubadour fields form a complex of giant gas-condensate accumulations located in the Timor Sea some 450 km northwest of Darwin. Left unappraised for almost a quarter of a century since discovery, recently renewed attention has brought these stranded hydrocarbon accumulations to the point of comm-ercialisation.A focussed appraisal program during 1997–1999 driven by expectations of growth in LNG and domestic gas markets, involved the acquisition and processing of an extensive grid of modern 2D seismic and the drilling, coring and testing of three wells. The aim of this program was to quantify better both in-place hydrocarbon volumes (reservoir properties and their distribution) and hydrocarbon recovery efficiency (gas quality and deliverability). Maximum value has been extracted from these data via a combination of deterministic and probabilistic methods, and the integration of analyses across all disciplines.This paper provides an overview of these efforts, describes the fields and details major subsurface uncertainties. Key aspects are:3D, object-based geological modelling of the reservoir, covering the spectrum of plausible sedimentological interpretations.Convolution of rock properties, derived from seismic (AVO) inversion, with 3D geological model realisations to define reservoir properties in inter-well areas.Incorporation of faults (both seismically mapped and probabilistically modelled sub-seismic faults) into both the static 3D reservoir models and the dynamic reservoir simulations.Interpretation of a tilted gas-water contact apparently arising from flow of water in the Plover aquifer away from active tectonism to the north.Extensive gas and condensate fluid analysis and modelling.Scenario-based approach to dynamic modelling.In summary, acquisition of an extensive suite of quality data during the past two-three years coupled with novel, integrated, state-of-the-art analysis of the subsurface has led to a major increase in estimates of potentially recoverable gas and condensate. Improved volumetric confidence in conjunction with both traditional and innovative engineering design (e.g. Floating Liquefied Natural Gas technology) has made viable a range of possible commercial developments from 2005 onwards.
INNOVATIONS IN SUBSEA DEVELOPMENT AND OPERATION
Authors: Henry W.C. , Hyden A.M. , Williams S.L.
Published: August 2017

Esso Australia Ltd on behalf of the Esso/BHP joint venture, recently completed Australia's first deep- water oil and gas development, Blackback, in 395 m water depth in eastern Bass Strait. Esso used a phased development approach and an innovative development concept to mitigate the effect of reserves uncertainty. The development consists of three wells in daisy-chain formation tied back to the existing Mackerel platform, 23 km distant. The development also used innovative approaches for installation of flexible flowline and umbilical jumpers from the drilling rig, management of hydrates in the production flowline and control system integration.In the same time frame, Esso repaired the failed electro-hydraulic control systems of two 10-year-old subsea wells. The repair program used an innovative approach to fault diagnosis and field work.
BENCHMARKING TO SET FIELD-LEVEL COST SAVINGS TARGETS AND SUCCESSFUL METHODS TO REDUCE FIELD OPERATING COSTS
Authors: Ziff P.H.
Published: August 2017

Oil and gas operators have been forced by rising investor expectations and a maturing resource base to both improve operating standards and reduce the cost of operations. During the past five years, the author's company has executed 20 studies in the US and Canada, examining the costs and methods of oil and gas operations for nearly 2,000 fields, for over 100 exploration and production companies. These studies cover more than a dozen basins from the Gulf of Mexico (Shelf and deepwater) to Alaska, including most producing basins in the US lower 48 states and Western Canada. They focus on developing an understanding of leading practices of successful operators, and identifying areas for remedial action to enhance cash flow.The paper examines various methods operators use to identify specific high cost areas for remedial action, and detail examples of successful operations. The focus will be on cost saving opportunities and practices utilised in offshore operations (Shelf and deepwater).
THE KYOTO PROTOCOL- THREATS AND OPPORTUNITIES
Authors: Beresford R. , Waller S.
Published: August 2017

In 1997, Australia signed the Kyoto Protocol under which it had been assigned what will become a legally binding emissions cap of 108% of its 1990 emissions. This target may be appropriate for our national circumstances but will be challenging to meet. This paper examines the way Woodside Energy Ltd is addressing the threats and opportunities raised by the Kyoto Protocol.The major risk to Woodside's business arises from the division of the Protocol into Annex B and non-Annex B. Australia is in Annex B, which is composed primarily of developed countries that have assigned emission amounts that will be legally binding when the protocol comes into force and is ratified.Meeting the Australian target and the global greenhouse emission reduction objective will require increasing the substitution of gas into national fuel mixes. Natural gas, including LNG, has the lowest lifecycle emissions of any fossil fuel.The Australian LNG industry is the only major Annex B supplier of LNG to Japan and thus would be at a severe competitive disadvantage if the costs of unilaterally imposed abatement policies and measures were applied to the industry in Australia that were not applied to its international competitors. The LNG industry is seeking differential treatment to alleviate this risk. Woodside has proposed a solution, put forward in this paper, that a scheme be negotiated into the Protocol at CoP6, allowing for the repatriation of credits from the LNG fuel cycle to the exporting country. This would permit fair competition across all LNG exporters.Woodside is keen to undertake its fair share of emission reduction and has already implemented some projects that have been successful in this regard. Further implementation of beyond no regrets projects relies on the Commonwealth resolving the recognition for early action question. A trial framework for making decisions on early abatement projects is described.Woodside is also investigating potential opportunities arising from the Protocol. Progress is reported on early investigation into clean development mechanism (CDM) projects and greenhouse abatement research and development (R&D). Sink enhancement studies are nearly complete and a detailed business case is under preparation.
MARINE SEISMIC SURVEYS— A STUDY OF ENVIRONMENTAL IMPLICATIONS
Authors: McCauley R.D. , Fewtrell J. , Duncan A.J. , Jenner C. , Jenner M-N. , Penrose J.D. , Prince R.I.T. , Adhitya A. , Murdoch J. , McCabe K.
Published: August 2017

An experimental program was run by the Centre for Marine Science and Technology of Curtin University between March 1996 and October 1999 to study the environmental implications of offshore seismic survey noise. This work was initiated and sponsored by the Australian Petroleum Production and Exploration Association. The program:characterised air gun signal measurements; modelled air gun array sources and horizontal air gun signal propagation;developed an 'exposure model' to predict the scale of potential biological effects for a given seismic survey over its duration;made observations of humpback whales traversing a 3D seismic survey;carried out experiments of approaching humpback whales with a single operating air gun;carried out trials with an air gun approaching a cage containing sea turtles, fishes or squid; andmodelled the response of fish hearing systems to airgun signals.The generalised response of migrating humpback whales to a 3D seismic vessel was to take some avoidance manoeuvre at >4 km then to allow the seismic vessel to pass no closer than 3 km. Humpback pods containing cows which were involved in resting behaviour in key habitat types, as opposed to migrating animals, were more sensitive and showed an avoidance response estimated at 7−12 km from a large seismic source. Male humpbacks were attracted to a single operating air gun due to what was believed the similarity of an air gun signal and a whale breaching event (leaping clear of the water and slamming back in). Based on the response of captive animals to an approaching single air gun and scaling these results, indicated sea turtles displayed a general 'alarm' response at an estimated 2 km range from an operating seismic vessel and behaviour indicative of avoidance estimated at 1 km. Similar trials with captive fishes showed a generic fish 'alarm' response of swimming faster, swimming to the bottom, tightening school structure, or all three, at an estimated 2−5 km from a seismic source. Modelling the fish ear predicted that at ranges
COAL SEAM METHANE—MEETING THE REQUIREMENTS OF BUYERS, FINANCIERS AND REGULATORS
Authors: Dighton P.F.
Published: August 2017

Significant work is taking place in Queensland and New South Wales to make the recovery of natural gas from coal seams (Coal Seam Methane) a viable industry. At this stage there are still some daunting hurdles to overcome. Australian buyers and financiers remain sceptical on resource risk and continuity of supply issues. In the USA commercial production has been taking place for 20 years, but the industry was only able to achieve credibility and viability by relying on tax breaks. Unfortunately, the same type of government incentives are not present in Australia. Whether, in the absence of these incentives, Australian producers can harness the resource on an economic basis remains to be seen.
1999 EXPLORATION REVIEW
Authors: Muir W.F.
Published: August 2017

Over the years, many issues have confronted the industry, and affected its approach to business. A brief analysis of seismic and exploration drilling levels over the past four decades demonstrates how marked these effects have been. During 1999, fewer wells have been drilled onshore in Australia than for any year since 1979. This is due in large part to the refusal of some State Governments to award newly gazetted acreage due to native title concerns. The solution required is a legislative one. Offshore drilling, however, is at a historically high level, and during 1999, had a success rate of one in five. Successes in both the onshore and offshore were restricted to currently producing basins.
Detection, prevalence and severity of upper canopy infection on mature Brassica napus plants caused by Leptosphaeria maculans in Australia
Authors: Sprague Susan J. , Marcroft Stephen J. , Lindbeck Kurt D. , Ware Andrew H. , Khangura Ravjit K. , Van de Wouw Angela P.
Published: August 2017

Blackleg, caused by Leptosphaeria maculans, is the main disease constraint for canola production in Australia. The fungus infects all aboveground and belowground parts of the canola plant. Yield loss in Australia and worldwide is generally associated with cankers at the crown, which arise from leaf infections during the early stages of seedling growth. Infection of flowers, peduncles, siliques, main stems and branches, with resultant lesions and canker formation, are typically uncommon symptoms. We propose the term ‘upper canopy infection’ to encompass symptoms on all of these plant parts because they generally occur together on the same plant and appear after the plant has undergone elongation. Branch and stem lesions observed in a commercial crop in 2010 were confirmed as L. maculans. Since then, assessment of upper canopy symptoms at 25 sites across the canola-producing regions of Australia between 2011 and 2016 show that symptoms are more prevalent, although they differed between sites and seasons. In 2011, symptoms were present at a single site, and this increased to seven sites in 2013 and 23 sites in 2016. Preliminary data indicate that infection arises from both ascospore and pycnidiospore inoculum, and that earlier onset of flowering is a key risk factor for more severe upper canopy infection. Evidence suggests that host genetic resistance may be an effective control for upper canopy infection.
Estimating nitrogen excretion and deposition by lactating cows in grazed dairy systems
Authors: Aarons Sharon R. , Gourley Cameron J. P. , Powell J. Mark , Hannah Murray C.
Published: August 2017

Large N surpluses are a feature of most dairy farms worldwide. Despite the predominance of grazing systems in Australia, increasing animal densities and greater reliance on purchased feed mean that feed nutrient inputs and the role of grazing animals in N flows and deposited loads have grown. However, quantifying nutrient intakes and N excretion is difficult on commercial farms due to challenges in estimating pasture dry matter (DM) intake by grazing cattle. The aim of the present study was to quantify for commercial dairy farms, N excreted by lactating herds, the relative amounts of excreta N versus farm N inputs, and N loads deposited to different within-farm locations. Data were collected on at least five occasions from 43 diverse grazing system farms located in different climatic zones. An animal performance method for estimating annual DM intake was modified to calculate daily N intake and excretion and animal feed N use efficiency (NUE; milk N secreted/feed N intake). On average, these herds received 52% of their energy requirements from supplementary feeds despite the grazing base. Mean N intake (545 g cow–1 day–1), which greatly exceeded recommended dietary intakes, resulted in mean excretion of 433 g N cow–1 day–1 and low mean NUE (21%; range 11–39%). Calculated annual N flows through the lactating herds were equivalent to 69% of total N inputs onto these farms. When excreted N was apportioned to the locations visited by the lactating herds, deposition to pasture paddocks was not uniform. Almost 50% more excreted N was deposited to paddocks that were closer to the dairy shed, and approximately twice as much N was returned to feedpads and holding areas as deposited in dairy sheds and yards, with the potential for N accumulation and loss in these places. On average, 20% more N was deposited as excreta on pasture paddocks by the lactating herd than was applied as commercial fertiliser (168 vs 141 kg N ha–1 respectively). These results demonstrate that quantifying excreta N loads and spatial nutrient distribution by lactating cows can assist in improving N management in grazing system dairy farms.
High-precision registration between zebrafish brain atlases using symmetric diffeomorphic normalization
Authors: Marquart Gregory D. , Tabor Kathryn M. , Horstick Eric J. , Brown Mary , Geoca Alexandra K. , Polys Nicholas F. , Nogare Damian Dalle , Burgess Harold A.
Published: August 2017

Atlases provide a framework for spatially mapping information from diverse sources into a common reference space. Specifically, brain atlases allow annotation of gene expression, cell morphology, connectivity, and activity. In larval zebrafish, advances in genetics, imaging, and computational methods now allow the collection of such information brain-wide. However, due to technical considerations, disparate datasets may use different references and may not be aligned to the same coordinate space. Two recent larval zebrafish atlases exemplify this problem: Z-Brain, containing gene expression, neural activity, and neuroanatomical segmentations, was acquired using immunohistochemical stains, while the Zebrafish Brain Browser (ZBB) was constructed from live scans of fluorescent reporters in transgenic larvae. Although different references were used, the atlases included several common transgenic patterns that provide potential “bridges” for transforming each into the other's coordinate space. We tested multiple bridging channels and registration algorithms and found that the symmetric diffeomorphic normalization algorithm improved live brain registration precision while better preserving cell morphology than B-spline-based registrations. Symmetric diffeomorphic normalization also corrected for tissue distortion introduced during fixation. Multi-reference channel optimization provided a transformation that enabled Z-Brain and ZBB to be co-aligned with precision of approximately a single cell diameter and minimal perturbation of cell and tissue morphology. Finally, we developed software to visualize brain regions in 3 dimensions, including a virtual reality neuroanatomy explorer. This study demonstrates the feasibility of integrating whole brain datasets, despite disparate reference templates and acquisition protocols, when sufficient information is present for bridging. Increased accuracy and interoperability of zebrafish digital brain atlases will facilitate neurobiological studies.
Bayes Forest: a data-intensive generator of morphological tree clones
Authors: Potapov Ilya , Järvenpää Marko , Åkerblom Markku , Raumonen Pasi , Kaasalainen Mikko
Published: August 2017

Detailed and realistic tree form generators have numerous applications in ecology and forestry. For example, the varying morphology of trees contributes differently to formation of landscapes, natural habitats of species, and eco-physiological characteristics of the biosphere. Here, we present an algorithm for generating morphological tree “clones” based on the detailed reconstruction of the laser scanning data, statistical measure of similarity, and a plant growth model with simple stochastic rules. The algorithm is designed to produce tree forms, i.e., morphological clones, similar (and not identical) in respect to tree-level structure, but varying in fine-scale structural detail. Although we opted for certain choices in our algorithm, individual parts may vary depending on the application, making it a general adaptable pipeline. Namely, we showed that a specific multipurpose procedural stochastic growth model can be algorithmically adjusted to produce the morphological clones replicated from the target experimentally measured tree. For this, we developed a statistical measure of similarity (structural distance) between any given pair of trees, which allows for the comprehensive comparing of the tree morphologies by means of empirical distributions describing the geometrical and topological features of a tree. Finally, we developed a programmable interface to manipulate data required by the algorithm. Our algorithm can be used in a variety of applications for exploration of the morphological potential of the growth models (both theoretical and experimental), arising in all sectors of plant science research.
De-Constitutionalising Collective Labour Rights: The Case of Greece
Authors: Katsaroumpas Ioannis
Published: August 2017

Since 2010, multiple waves of EU/IMF-imposed legislative reforms have led to extensive deregulation or ‘de-construction’ of Greek collective labour law. While there are many accounts of the Greek reforms, no systematic attention has been devoted to the following paradox: how is such a de-construction possible, in a jurisdiction enjoying a strong domestic constitutionalisation of labour rights, and apparently observing multiple transnational collective labour rights, derived from the CFREU, ECHR, and ILO Conventions? This article sets out to investigate the constitutional dynamics behind the process termed here as ‘de-constitutionalisation’ of collective labour rights. It seeks to add two contributions to the existing literature. Firstly, taking its cue from Eric Tucker’s mapping of multi-level ‘capital’ and ‘labour’ constitutions developed in the Canadian context, it suggests that the Greek case of de-constitutionalisation is the cumulative result of a specific configuration of interactions between ‘aggressive’ EU-IMF conditionality at the level of transnational capital rights, and ‘defensive’ articulation of labour rights at domestic and transnational levels. As will be seen, these interactions disguise an asymmetric clash between a strong constutionalisation of capital rights at transnational level, and a weak constitutionalisation of labour rights at both transnational and domestic levels. Secondly, the article projects the Greek case onto the broader constitutionalisation debate, which questions the desirability of constitutionalising collective labour rights as an effective response to neo-liberal policies and laws. While submitting that the Greek developments support the sceptical side of this debate, in particular by providing a continental European confirmation of Tucker’s thesis, the article offers several new reflections of relevance to the constitutionalisation debate.
The scatter, residual correlations and curvature of the sparc baryonic Tully–Fisher relation
Authors: Desmond Harry
Published: August 2017

In recent work, Lelli et al. argue that the tightness of the baryonic Tully–Fisher relation (BTFR) of the sparc galaxy sample, and the weakness of the correlation of its residuals with effective radius, pose challenges to Λ cold dark matter cosmology. In this Letter, we calculate the statistical significance of these results in the framework of halo abundance matching, which imposes a canonical galaxy–halo connection. Taking full account of sample variance among sparc-like realizations of the parent halo population, we find the scatter in the predicted BTFR to be 3.6σ too high, but the correlation of its residuals with galaxy size to be naturally weak. Further, we find abundance matching to generate BTFR curvature in 3.0σ disagreement with the data, and a fraction of galaxies with non-flat rotation curves somewhat larger than observed.
Incorporating Adjuvants with Captan to Manage Common Apple Diseases
Authors: Abbott Chelsi P. , Beckerman Janna L.
Published: August 2017

Captan has become an increasingly important fungicide in the management of common apple diseases such as apple scab (Venturia inaequalis) and bitter rot (Colletotrichum spp.) due to the low risk of fungicide resistance evolving in either pathogen population to this product. Restrictions on the amount of captan that can be applied per season limits the amount and the number of applications a grower may use, resulting in control failures during high disease pressure years. This 3-year field study evaluated how adjuvants combined with captan affected the incidence and severity of apple scab and bitter rot on two different apple cultivars. Results showed that Li700 plus captan and Bond Max plus captan reduced disease incidence of apple scab and bitter rot in years with moderate to high disease pressure by increasing the coverage and retention of captan. The addition of these adjuvants also resulted in possible yield losses due to russetting caused by phytotoxicity. The overall benefits of incorporating adjuvants with captan based on this study could reduce disease incidence while potentially saving a grower up to $5,329 ha–1due to fungicide reduction.
Stacked Generalization: An Introduction to Super Learning
Authors: Naimi Ashley I. , Balzer Laura B.
Published: August 2017

Stacked generalization is an ensemble method that allows researchers to combine several different prediction algorithms into one. Since its introduction in the early 1990s, the method has evolved several times into what is now known as “Super Learner”. Super Learner usesV-fold cross-validation to build the optimal weighted combination of predictions from a library of candidate algorithms. Optimality is defined by a user-specified objective function, such as minimizing mean squared error or maximizing the area under the receiver operating characteristic curve. Although relatively simple in nature, use of the Super Learner by epidemiologists has been hampered by limitations in understanding conceptual and technical details. We work step-by-step through two examples to illustrate concepts and address common concerns.
Characterizing a thermostable Cas9 for bacterial genome editing and silencing
Authors: Mougiakos Ioannis , Mohanraju Prarthana , Bosma Elleke F. , Vrouwe Valentijn , Bou Max Finger , Naduthodi Mihris I. S. , Gussak Alexander , Brinkman Rudolf B. L. , Kranenburg Richard van , der Oost John van
Published: August 2017

CRISPR-Cas9 based genome engineering tools have revolutionized fundamental research and biotechnological exploitation of both eukaryotes and prokaryotes. However, the mesophilic nature of the established Cas9 systems does not allow for applications that require enhanced stability, including engineering at elevated temperatures. Here, we identify and characterize ThermoCas9: an RNA-guided DNA-endonuclease from the thermophilic bacterium Geobacillus thermodenitrificans T12. We show that ThermoCas9 is active in vitro between 20°C and 70°C, a temperature range much broader than that of the currently used Cas9 orthologues. Additionally, we demonstrate that ThermoCas9 activity at elevated temperatures is strongly associated with the structure of the employed sgRNA. Subsequently, we develop ThermoCas9-based engineering tools for gene deletion and transcriptional silencing at 55°C in Bacillus smithii and for gene deletion at 37°C in Pseudomonas putida. Altogether, our findings provide fundamental insights into a thermophilic CRISPR-Cas family member and establish the first Cas9-based bacterial genome editing and silencing tool with a broad temperature range.
SPIN1 promotes tumorigenesis by blocking the uL18-MDM2-p53 pathway
Authors: Fang Ziling , Liao Jun-Ming , Cao Bo , Deng Jun , Plummer Kevin D , Liao Peng , Liu Tao , Zeng Shelya X. , Xiong Jianping , Lu Hua
Published: August 2017

Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of cancer cells by sequestering uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity towards p53. SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. Analysis of cancer genomic databases suggests that SPIN1 is highly expressed in several human cancers, and its overexpression is positively correlated with poor prognosis in cancer patients. Altogether, our findings reveal that the oncogenic property of SPIN1 is highly attributed to its negative regulation of uL18, leading to p53 inactivation.
Frequent paramutation-like features of natural epialleles in tomato
Authors: Gouil Quentin , Baulcombe David
Published: August 2017

Freakish and rare or the tip of the iceberg? Both phrases have been used to refer to paramutation, an epigenetic drive that contravenes Mendel's first law of segregation. Although its underlying mechanisms are beginning to unravel, its understanding relies only on a few examples that may involve transgenes or artificially generated epialleles. By using DNA methylation of introgression lines as an indication of past paramutation, we reveal that the paramutation-like properties of the H06 locus in hybrids of Solanum lycopersicum and a range of tomato relatives and cultivars depend on the timing of sRNA production and conform to an RNA-directed mechanism. In addition, by scanning the methylomes of tomato introgression lines for shared regions of differential methylation that are absent in the S. lycopersicum parent, we identify thousands of candidate regions for paramutation-like behaviour. The methylation patterns for a subset of these regions segregate with non Mendelian ratios, consistent with secondary paramutation-like interactions to variable extents depending on the locus. Together these results demonstrate that paramutation-like epigenetic interactions are common for natural epialleles in tomato, but vary in timing and penetrance.
BCL-3 enhances β-catenin signalling in colorectal tumour cells promoting a cancer stem cell phenotype
Authors: Legge Danny N , Shephard Alex P , Collard Tracey J , Greenhough Alexander , Chambers Adam C , Clarkson Richard W , Paraskeva Christos , Williams Ann C
Published: August 2017

Increased nuclear BCL-3 (a key regulator of inflammation and NF-κB signalling when associated with p50 or p52 homodimers) has been reported in a subset of colorectal cancers, but its role in colorectal tumorigenesis remains poorly understood. Interestingly, recent studies have highlighted the importance of the interplay between NF-κB signalling and the Wnt/β-catenin pathway in colorectal epithelial cells, reporting that non-stem cells engineered to undergo high levels of Wnt and NF-κB signalling can de-differentiate, initiating tumours in mice. Here we show that BCL-3 is an important co-activator of β-catenin/TCF-mediated transcriptional activity in colorectal cancer cells, increasing expression of Wnt-regulated intestinal stem cell genes. We demonstrate RNAi-mediated BCL-3 suppression reduced β-catenin/TCF-dependent transcription and the expression of intestinal stem cell genes and Wnt targetsLGR5andASCL2. Further we show that BCL-3 promotes the stem cell phenotype in colorectal cancer cells by increasing colorectal spheroid and tumoursphere formation in 3D culture conditions. Our data suggest that targeting BCL-3 may represent an exciting new approach for CRC treatment, particularly as it acts downstream of frequently mutated APC and β-catenin.
Precise, pan-cancer discovery of gene fusions reveals a signature of selection in primary tumors
Authors: Freeman Donald Eric , Hsieh Gillian Lee , Howard Jonathan Michael , Lehnert Erik , Salzman Julia
Published: August 2017

Short Abstract

The extent to which gene fusions function as drivers of cancer remains a critical open question in cancer biology. In principle, transcriptome sequencing provided by The Cancer Genome Atlas (TCGA) enables unbiased discovery of gene fusions and post-analysis that informs the answer to this question. To date, such an analysis has been impossible because of performance limitations in fusion detection algorithms. By engineering a new, more precise, algorithm and statistical approaches to post-analysis of fusions called in TCGA data, we report new recurrent gene fusions, including those that could be druggable; new candidate pan-cancer oncogenes based on their profiles in fusions; and prevalent, previously overlooked, candidate oncogenic gene fusions in ovarian cancer, a disease with minimal treatment advances in recent decades. The novel and reproducible statistical algorithms and, more importantly, the biological conclusions open the door for increased attention to gene fusions as drivers of cancer and for future research into using fusions for targeted therapy.
Deep learning: Using machine learning to study biological vision
Authors: Majaj Najib J. , Pelli Denis G.
Published: August 2017

Today many vision-science presentations employ machine learning, especially the version called “deep learning”. Many neuroscientists use machine learning to decode neural responses. Many perception scientists try to understand how living organisms recognize objects. To them, deep neural networks offer benchmark accuracies for recognition of learned stimuli. Originally machine learning was inspired by the brain. Today, machine learning is used as a statistical tool to decode brain activity. Tomorrow, deep neural networks might become our best model of brain function. This brief overview of the use of machine learning in biological vision touches on its strengths, weaknesses, milestones, controversies, and current directions. Here, we hope to help vision scientists assess what role machine learning should play in their research.
RNA editing of CAPS1 regulates synaptic vesicle organization, release and retrieval
Authors: Ulbricht Randi J. , Sun Sarah J. , DelBove Claire E. , Kitko Kristina E. , Rehman Saad C. , Wang Michelle Y. , Lazarenko Roman M. , Zhang Qi , Emeson Ronald B.
Published: August 2017

Calcium-dependent activator protein for secretion 1 (CAPS1) facilitates the docking and priming of synaptic and dense core vesicles. A conserved hairpin structure in the CAPS1 pre-mRNA allows an post-transcriptional adenosine-to-inosine RNA editing event to alter a genomically-encoded glutamate to a glycine codon. Functional comparisons of CAPS1 protein isoforms in primary hippocampal neurons show that elevation of edited CAPS1 isoforms facilitates presynaptic vesicle clustering and turnover. Conversely, non-edited CAPS1 isoforms slow evoked release, increase spontaneous fusion, and loosen the clustering of synaptic vesicles. Therefore, CAPS1 editing promotes organization of the vesicle pool in a way that is beneficial for evoked release, while non-edited isoforms promote more lax vesicle organization that widens distribution, attenuates evoked release and eases the control of spontaneous fusion. Overall, RNA editing of CAPS1 is a mechanism to fine tune neurotransmitter release.

IMPACT STATEMENT

Post-transcriptional RNA editing of CAPS1 is a mechanism to regulate neurotransmitter release from synaptic vesicles.
The Anti-Epileptic Ketogenic Diet Alters Hippocampal Transporter Levels and Reduces Adiposity in Aged Rats
Authors: Hernandez Abbi R. , Hernandez Caesar M. , Campos Keila T. , Truckenbrod Leah M. , Sakarya Yasemin , McQuail Joseph A. , Carter Christy S. , Bizon Jennifer L. , Maurer Andrew P. , Burke Sara N.
Published: August 2017

Nutritional ketosis is induced by high fat/low carbohydrate dietary regimens, which produce high levels of circulating ketone bodies, shifting metabolism away from glucose utilization. While ketogenic diets (KD) were initially introduced to suppress seizures, they are garnering attention for their potential to treat a myriad of neurodegenerative and metabolic disorders that are associated with advanced age. The feasibility and physiological impact of implementing a long-term KD in old animals, however, has not been systematically examined. In this study, young and aged rats consumed a calorically- and nutritionally-matched KD or control diet for 12 weeks. All KD-fed rats maintained higher levels of β-hydroxybutyrate (BHB) and lower levels of glucose relative to controls. However, it took the aged rats longer to reach asymptotic levels of BHB compared to young animals. Moreover, KD-fed rats had significantly less visceral white and brown adipose tissue than controls without a loss of lean mass. Interestingly, the KD lead to significant alterations in protein levels of hippocampal transporters for monocarboxylates, glucose and vesicular glutamate and GABA. Most notably, the age-related decline in vesicular glutamate transporter expression was reversed by the KD. These data demonstrate the feasibility and potential benefits of KDs for treating age-associated neural dysfunction.
Behavioral and neural indices of affective coloring for neutral social stimuli
Authors: Grupe Daniel W. , Schaefer Stacey M. , Lapate Regina C. , Schoen Andrew J. , Gresham Lauren K. , Mumford Jeanette A. , Davidson Richard J.
Published: August 2017

Emotional processing often continues beyond the presentation of emotionally evocative stimuli, which can result in affective biasing or coloring of subsequently encountered events. Here, we describe neural correlates of affective coloring and examine how individual differences in affective style impact the magnitude of affective coloring. We conducted functional magnetic resonance imaging in 117 adults who passively viewed negative, neutral, and positive pictures presented 2s prior to neutral faces. Brain responses to neutral faces were modulated by the valence of preceding pictures, with greater activation for faces following negative (vs. positive) pictures in the amygdala, dorsomedial and lateral prefrontal cortex, ventral visual cortices, posterior superior temporal sulcus, and angular gyrus. Three days after the MRI scan, participants rated their memory and liking of previously encountered neutral faces. Individuals higher in trait positive affect and emotional reappraisal rated faces as more likable when preceded by emotionally arousing (negative or positive) pictures. Additionally, greater amygdala responses to neutral faces preceded by positively valenced pictures were associated with greater memory for these faces three days later. Collectively, these results reveal individual differences in how emotions spill over onto the processing of unrelated social stimuli, resulting in persistent and affectively biased evaluations of such stimuli.
Current geography masks dynamic history of gene flow during speciation in northern Australian birds
Authors: Peñalba Joshua V. , Joseph Leo , Moritz Craig
Published: August 2017

During early stages of speciation, genome divergence is greatly influenced by gene flow. As populations diverge, geography can allow or restrict gene flow in the form of barriers. Current geography, e.g. whether sister species are allopatric or parapatric, is often used to predict the potential for gene flow during the divergence process. We test the validity of this assumption in eight meliphagoid bird species codistributed across four regions. These regions are separated by known biogeographic barriers within and between northern Australia and Papua New Guinea. We find that bird populations across the same barrier have a range of divergence levels and probability of gene flow regardless of range connectivity. Geographic distance and maximum range connectivity over time can better predict divergence and probability of gene flow than whether populations are currently allopatric or parapatric. We also find support for a nonlinear decrease of the probability of gene flow during the divergence process. This implies that although gene flow influences divergence early in speciation, other factors associated with higher divergence restrict gene flow later in speciation. Current geography may then mislead inferences regarding potential for gene flow during speciation under a complex and dynamic history of geographic and reproductive isolation.
Inferring propensity amongst lung and breast carcinomas via overlapped gene expression profiles
Authors: Jaiswal Rajni , Dhakal Sabin , Jauhari Shaurya
Published: August 2017

Reconstruction of biological networks for topological analyses helps in correlation identification between various types of biomarkers. These networks have been vital components of System Biology in present era. Genes are the basic physical and structural unit of heredity. Genes act as instructions to make molecules called proteins. Alterations in the normal sequence of these genes are the root cause of various diseases and cancer is the prominent example disease caused by gene alteration or mutation. These slight alterations can be detected by microarray analysis. The high throughput data obtained by microarray experiments aid scientists in reconstructing cancer specific gene regulatory networks. The purpose of experiment performed is to find out the overlapping of the gene expression profiles of breast and lung cancer data, so that the common hub genes can be sifted and utilized as drug targets which could be used for the treatment of diseased conditions. In this study, first the differentially expressed genes have been identified (lung cancer and breast cancer), followed by a filtration approach and most significant genes are chosen using paired t-test and gene regulatory network construction. The obtained result has been checked and validated with the available databases and literature.
WDR88,CCDC11, andARPP21genes indulge profoundly in the desmoplastic retort to prostate and breast cancer metastasis
Authors: Jaiswal Rajni , Jauhari Shaurya , Rizvi S.A.M.
Published: August 2017

Microarray technology has unlocked doors to a multitude of open analysis problems that if conceived with efficacy may uncover varied genotypic and phenotypic traits. Algorithms belonging to different cultures in computer science have been applied to gene expression data to derive correlation and stratification parameters. While most outcomes are subject to clinical validation, majority of which get declined, the search for the precisely targeted therapeutic agents is still on. This paper is an effort in the similar direction and strives to delineate genes with significant stromal signatures. We suggest a corroborative indulgence of a human laterality disorder gene, CCDC11 in the metastasis, in addition to the role ofWDR88andARPP21genes has been further materialized in the analysis. Another standout aspect of the study has been the associated implications of the genes in rare disorders of male breast and female prostate cancers. There is also a threshold proposal that stratifies “safe” expression space for genes. Complimentarily, the manuscript serves as an expedient protocol for anyone seeking microarray data analysis, particularly in R.