Introduction: looking beyond the walls

In its consideration of the remarkable extent and variety of non-university researchers, this book takes a broader view of ‘knowledge’ and ‘research’ than in the many hot debates about today’s knowledge society, ‘learning age’, or organisation of research. It goes beyond the commonly held image of ‘knowledge’ as something produced and owned by the full-time experts to take a look at those engaged in active knowledge building outside the university walls

From error bounds to the complexity of first-order descent methods for convex functions

This paper shows that error bounds can be used as effective tools for deriving complexity results for first-order descent methods in convex minimization. In a first stage, this objective led us to revisit the interplay between error bounds and the Kurdyka-\L ojasiewicz (KL) inequality. One can show the equivalence between the two concepts for convex functions having a moderately flat profile near the set of minimizers (as those of functions with H\"olderian growth). A counterexample shows that the equivalence is no longer true for extremely flat functions. This fact reveals the relevance of an approach based on KL inequality. In a second stage, we show how KL inequalities can in turn be employed to compute new complexity bounds for a wealth of descent methods for convex problems. Our approach is completely original and makes use of a one-dimensional worst-case proximal sequence in the spirit of the famous majorant method of Kantorovich. Our result applies to a very simple abstract scheme that covers a wide class of descent methods. As a byproduct of our study, we also provide new results for the globalization of KL inequalities in the convex framework. Our main results inaugurate a simple methodology: derive an error bound, compute the desingularizing function whenever possible, identify essential constants in the descent method and finally compute the complexity using the one-dimensional worst case proximal sequence. Our method is illustrated through projection methods for feasibility problems, and through the famous iterative shrinkage thresholding algorithm (ISTA), for which we show that the complexity bound is of the form $O(q^{k})$ where the constituents of the bound only depend on error bound constants obtained for an arbitrary least squares objective with $\ell^1$ regularization

The influence of soil communities on the temperature sensitivity of soil respiration

Soil respiration represents a major carbon flux between terrestrial ecosystems and the atmosphere, and is expected to accelerate under climate warming. Despite its importance in climate change forecasts, however, our understanding of the effects of temperature on soil respiration (RS) is incomplete. Using a metabolic ecology approach we link soil biota metabolism, community composition and heterotrophic activity, to predict RS rates across five biomes. We find that accounting for the ecological mechanisms underpinning decomposition processes predicts climatological RS variations observed in an independent dataset (n = 312). The importance of community composition is evident because without it RS is substantially underestimated. With increasing temperature, we predict a latitudinal increase in RS temperature sensitivity, with Q10 values ranging between 2.33 ±0.01 in tropical forests to 2.72 ±0.03 in tundra. This global trend has been widely observed, but has not previously been linked to soil communities

Understanding the limits to generalizability of experimental evolutionary models.

Post print version of article deposited in accordance with SHERPA RoMEO guidelines. The final definitive version is available online at: http://www.nature.com/nature/journal/v455/n7210/abs/nature07152.htmlGiven the difficulty of testing evolutionary and ecological theory in situ, in vitro model systems are attractive alternatives; however, can we appraise whether an experimental result is particular to the in vitro model, and, if so, characterize the systems likely to behave differently and understand why? Here we examine these issues using the relationship between phenotypic diversity and resource input in the T7-Escherichia coli co-evolving system as a case history. We establish a mathematical model of this interaction, framed as one instance of a super-class of host-parasite co-evolutionary models, and show that it captures experimental results. By tuning this model, we then ask how diversity as a function of resource input could behave for alternative co-evolving partners (for example, E. coli with lambda bacteriophages). In contrast to populations lacking bacteriophages, variation in diversity with differences in resources is always found for co-evolving populations, supporting the geographic mosaic theory of co-evolution. The form of this variation is not, however, universal. Details of infectivity are pivotal: in T7-E. coli with a modified gene-for-gene interaction, diversity is low at high resource input, whereas, for matching-allele interactions, maximal diversity is found at high resource input. A combination of in vitro systems and appropriately configured mathematical models is an effective means to isolate results particular to the in vitro system, to characterize systems likely to behave differently and to understand the biology underpinning those alternatives

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration

BACKGROUND: HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: OBJECTIVES: To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes. DESIGN: A proof of concept double-masked randomized controlled study. PARTICIPANTS: 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA ≥ 20/60 in at least one eye, and a normal lipid profile. INTERVENTION: Simvastatin 40 mg/day or placebo, allocated 1:1. MAIN OUTCOME MEASURES: Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected. CONCLUSION/SIGNIFICANCE: Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065

Role of the PAS sensor domains in the Bacillus subtilis sporulation kinase KinA

Histidine kinases are sophisticated molecular sensors that are used by bacteria to detect and respond to a multitude of environmental signals. KinA is the major histidine kinase required for initiation of sporulation upon nutrient deprivation in Bacillus subtilis. KinA has a large N-terminal region (residues 1 to 382) that is uniquely composed of three tandem Per-ARNT-Sim (PAS) domains that have been proposed to constitute a sensor module. To further enhance our understanding of this "sensor" region, we defined the boundaries that give rise to the minimal autonomously folded PAS domains and analyzed their homo- and heteroassociation properties using analytical ultracentrifugation, nuclear magnetic resonance (NMR) spectroscopy, and multiangle laser light scattering. We show that PAS(A) self-associates very weakly, while PAS(C) is primarily a monomer. In contrast, PAS(B) forms a stable dimer (K-d [dissociation constant] o

A Preliminary Study on Robot-Assisted Ankle Rehabilitation for the Treatment of Drop Foot

This paper involves the use of a compliant ankle rehabilitation robot (CARR) for the treatment of drop foot. The robot has a bio-inspired design by employing four Festo Fluidic muscles (FFMs) that mimic skeletal muscles actuating three rotational degrees of freedom (DOFs). A trajectory tracking controller was developed in joint task space to track the predefined trajectory of the end effector. This controller was achieved by controlling individual FFM length based on inverse kinematics. Three patients with drop foot participated in a preliminary study to evaluate the potential of the CARR for clinical applications. Ankle stretching exercises along ankle dorsiflexion and plantarflexion (DP) were delivered for treating drop foot. All patients gave positive feedback in using this ankle robot for the treatment of drop foot, although some limitations exist. The proposed controller showed satisfactory accuracy in trajectory tracking, with all root mean square deviation (RMSD) values no greater than 0.0335 rad and normalized root mean square deviation (NRMSD) values less than 6.7%. These preliminary findings support the potentials of the CARR for clinical applications. Future work will investigate the effectiveness of the robot for treating drop foot on a large sample of subjects

Biosynthesis of copper carbonate nanoparticles by ureolytic fungi

In this research, the ureolytic fungi Neurospora crassa, Pestalotiopsis sp. and Myrothecium gramineum were investigated for the preparation of nanoscale copper carbonate and the role of fungal extracellular protein in such mineral formation. After incubation in urea-modified media, carbonate-laden fungal supernatants were used for the precipitation of copper carbonate, with experimental results agreeing closely with those obtained using geochemical modelling (Geochemist's Workbench). Compared with commercial and chemically synthesized copper carbonate, the minerals obtained using fungal supernatants were nanoscale and showed varying morphologies. It was found that extracellular protein played an important role in determining the size and morphology of the carbonate minerals precipitated, and after mixture with CuCl2 and resultant copper carbonate precipitation, more than 80% protein was removed from the N. crassa supernatant. Moreover, with addition of extracellular protein extracted from different fungal supernatants or standard bovine serum albumin, more than 96% of protein was removed by carbonate mineral precipitation. These results provide direct experimental evidence for the preparation of copper carbonate nanoparticles utilizing fungal ureolytic activity and show that fungal extracellular protein plays an important role in the formation and size of specific nano metal carbonates. Such a process provides opportunities for production of specific and/or novel metal carbonate nanoparticles of applied relevance, and as precursors of other useful biomineral products such as oxides.</p

Vision and visual history in elite-/near-elite level cricketers and rugby-league players

Background: The importance of optimal and/or superior vision for participation in high-level sport remains the subject of considerable clinical research interest. Here we examine the vision and visual history of elite/near-elite cricketers and rugby-league players. Methods: Stereoacuity (TNO), colour vision, and distance (with/without pinhole) and near visual acuity (VA) were measured in two cricket squads (elite/international-level, female, n=16; near-elite, male, n=23) and one professional rugby-league squad (male, n=20). Refractive error was determined, and details of any correction worn and visual history were recorded. Results: Overall, 63% had their last eye-examination within 2 years. However, some had not had an eye examination for 5 years, or had never had one (near-elite-cricketers: 30%; rugby-league players: 15%; elite-cricketers: 6%). Comparing our results for all participants to published data for young, optimally-corrected, non-sporting adults, distance VA was ~1 line of letters worse than expected. Adopting α=0.01, the deficit in distance-VA deficit was significant, but only for elite-cricketers (p0.02 for all comparisons). On average, stereoacuity was better than in young adults, but only in elite-cricketers (p<0.001; p=0.03, near-elite-cricketers; p=0.47, rugby-league -players). On-field visual issues were present in 27% of participants, and mostly (in 75% of cases) comprised uncorrected ametropia. Some cricketers (near-elite: 17.4%; elite: 38%) wore refractive correction during play but no rugby-league player did. Some individuals with prescribed correction choose not to wear it when playing. Conclusion: Aside from near stereoacuity in elite-cricketers, these basic visual abilities were not better than equivalent, published data for optimally-corrected adults. 20-25% exhibited sub-optimal vision, suggesting that the clearest possible vision might not be critical for participation at the highest levels in the sports of cricket or rugby-league. Although vision could be improved in a sizeable proportion of our sample, the impact of correcting these, mostly subtle, refractive anomalies on playing performance is unknown