Computational models in the age of large datasets.

Technological advances in experimental neuroscience are generating vast quantities of data, from the dynamics of single molecules to the structure and activity patterns of large networks of neurons. How do we make sense of these voluminous, complex, disparate and often incomplete data? How do we find general principles in the morass of detail? Computational models are invaluable and necessary in this task and yield insights that cannot otherwise be obtained. However, building and interpreting good computational models is a substantial challenge, especially so in the era of large datasets. Fitting detailed models to experimental data is difficult and often requires onerous assumptions, while more loosely constrained conceptual models that explore broad hypotheses and principles can yield more useful insights.Charles A King TrustThis is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.conb.2015.01.00

The Boundaries of Verifiable Accuracy, Robustness, and Generalisation in Deep Learning

In this work, we assess the theoretical limitations of determining guaranteed stability and accuracy of neural networks in classification tasks. We consider classical distribution-agnostic framework and algorithms minimising empirical risks and potentially subjected to some weights regularisation. We show that there is a large family of tasks for which computing and verifying ideal stable and accurate neural networks in the above settings is extremely challenging, if at all possible, even when such ideal solutions exist within the given class of neural architectures

Dynamics and Excitation of Radio Galaxy Emission-Line Regions - I. PKS 2356-61

Results are presented from a programme of detailed longslit spectroscopic observations of the extended emission-line region (EELR) associated with the powerful radio galaxy PKS 2356-61. The observations have been used to construct spectroscopic datacubes, which yield detailed information on the spatial variations of emission-line ratios across the EELR, together with its kinematic structure. We present an extensive comparison between the data and results obtained from the MAPPINGS II shock ionization code, and show that the physical properties of the line-emitting gas, including its ionization, excitation, dynamics and overall energy budget, are entirely consistent with a scenario involving auto-ionizing shocks as the dominant ionization mechanism. This has the advantage of accounting for the observed EELR properties by means of a single physical process, thereby requiring less free parameters than the alternative scheme involving photoionization by radiation from the active nucleus. Finally, possible mechanisms of shock formation are considered in the context of the dynamics and origin of the gas, specifically scenarios involving infall or accretion of gas during an interaction between the host radio galaxy and a companion galaxy.Comment: 35 pages, LaTeX, uses aas2pp4.sty file, includes 9 PostScript figures. Two additional colour plates are available from the authors upon request. Accepted for publication in the Astrophysical Journa

Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation

The NLRP3 inflammasome is a cytosolic complex sensing phagocytosed material and various damage-associated molecular patterns, triggering production of the pro-inflammatory cytokines interleukin-1 beta (IL)-1β and IL-18 and promoting pyroptosis. Here, we characterize glutathione transferase omega 1-1 (GSTO1-1), a constitutive deglutathionylating enzyme, as a regulator of the NLRP3 inflammasome. Using a small molecule inhibitor of GSTO1-1 termed C1-27, endogenous GSTO1-1 knockdown, and GSTO1-1−/− mice, we report that GSTO1-1 is involved in NLRP3 inflammasome activation. Mechanistically, GSTO1-1 deglutathionylates cysteine 253 in NIMA related kinase 7 (NEK7) to promote NLRP3 activation. We therefore identify GSTO1-1 as an NLRP3 inflammasome regulator, which has potential as a drug target to limit NLRP3-mediated inflammation.We would like to acknowledge the following grants: the National Health and Medical Research Council of Australia (NHMRC) is thanked for Project Grant APP1124673 to P.G.B., M.G.C., and L.A.J.O.; Principal Research Fellowship 1117602 to J.B.B.; and NHMRC Project Grant APP1156455 to J.B.B., P.G.B., and M.G.C. The O’Neill laboratory acknowledges the following grant support: European Research Council (ECFP7-ERC-MICROINNATE) and Science Foundation Ireland Investigator Award (SFI 12/IA/1531)

Evidence synthesis as the key to more coherent and efficient research

<p>Abstract</p> <p>Background</p> <p>Systematic review and meta-analysis currently underpin much of evidence-based medicine. Such methodologies bring order to <it>previous </it>research, but <it>future </it>research planning remains relatively incoherent and inefficient.</p> <p>Methods</p> <p>To outline a framework for evaluation of health interventions, aimed at increasing coherence and efficiency through i) making better use of information contained within the existing evidence-base when designing future studies; and ii) maximising the information available and thus potentially reducing the need for future studies.</p> <p>Results</p> <p>The framework presented insists that an up-to-date meta-analysis of existing randomised controlled trials (RCTs) should always be considered before future trials are conducted. Such a meta-analysis should inform critical design issues such as sample size determination. The contexts in which the use of individual patient data meta-analysis and mixed treatment comparisons modelling may be beneficial before further RCTs are conducted are considered. Consideration should also be given to how any newly planned RCTs would contribute to the totality of evidence through its incorporation into an updated meta-analysis. We illustrate how new RCTs can have very low power to change inferences of an existing meta-analysis, particularly when between study heterogeneity is taken into consideration.</p> <p>Conclusion</p> <p>While the collation of existing evidence as the basis for clinical practice is now routine, a more coherent and efficient approach to planning future RCTs to strengthen the evidence base needs to be developed. The framework presented is a proposal for how this situation can be improved.</p

Annual estimates of occupancy for bryophytes, lichens and invertebrates in the UK, 1970–2015

Here, we determine annual estimates of occupancy and species trends for 5,293 UK bryophytes, lichens, and invertebrates, providing national scale information on UK biodiversity change for 31 taxonomic groups for the time period 1970 to 2015. The dataset was produced through the application of a Bayesian occupancy modelling framework to species occurrence records supplied by 29 national recording schemes or societies (n = 24,118,549 records). In the UK, annual measures of species status from fine scale data (e.g. 1 × 1 km) had previously been limited to a few taxa for which structured monitoring data are available, mainly birds, butterflies, bats and a subset of moth species. By using an occupancy modelling framework designed for use with relatively low recording intensity data, we have been able to estimate species trends and generate annual estimates of occupancy for taxa where annual trend estimates and status were previously limited or unknown at this scale. These data broaden our knowledge of UK biodiversity and can be used to investigate variation in and drivers of biodiversity change

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

No abstract available

Coupled atmosphere–mixed layer ocean response to ocean heat flux convergence along the Kuroshio Current Extension

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Climate Dynamics 36 (2011): 2295-2312, doi:10.1007/s00382-010-0764-8.The winter response of the coupled atmosphere-ocean mixed layer system to anomalous geostrophic ocean heat flux convergence in the Kuroshio Extension is investigated by means of experiments with an atmospheric general circulation model coupled to an entraining ocean mixed layer model in the extra-tropics. The direct response consists of positive SST anomalies along the Kuroshio Extension and a baroclinic (low-level trough and upper-level ridge) circulation anomaly over the North Pacific. The low-level component of this atmospheric circulation response is weaker in the case without coupling to an extratropical ocean mixed layer, especially in late winter. The inclusion of an interactive mixed layer in the tropics modifies the direct coupled atmospheric response due to a northward displacement of the Pacific Inter-Tropical Convergence Zone which drives an equivalent barotropic anomalous ridge over the North Pacific. Although the tropically-driven component of the North Pacific atmospheric circulation response is comparable to the direct response in terms of sea level pressure amplitude, it is less important in terms of wind stress curl amplitude due to the mitigating effect of the relatively broad spatial scale of the tropically-forced atmospheric teleconnection.We gratefully acknowledge financial support from NOAA’s Office of Global Programs (grant to C. Deser and Y.-O. Kwon). Y.-O. Kwon is also supported through the Claudia Heyman Fellowship of the WHOI Ocean Climate Change Institute

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure