The use of superparamagnetic nanoparticles for prosthetic biofilm prevention

As with all surgical procedures, implantation comes with the added risk of infection. The goal of this in vitro study was to explore the use of superparamagnetic iron oxide nanoparticles (SPION) as a multifunctional platform to prevent biofilm formation. Results showed for the first time decreased Staphylococcus epidermidis numbers when exposed to 100 μg/ml of SPION for 12 hours and this trend continued for up to 48 hours. Prevention of colony assembly, a prerequisite to biofilm formation, was also observed at lower SPION dosages of 10 μg/ml after 12 hours. Coupled with previous studies demonstrating enhanced bone cell functions in the presence of the same concentration of SPION, the present results provided much promise for the use of SPION for numerous anti-infection orthopedic applications

The chiral ring of AdS3/CFT2 and the attractor mechanism

We study the moduli dependence of the chiral ring in N = (4,4) superconformal field theories, with special emphasis on those CFTs that are dual to type IIB string theory on AdS3xS3xX4. The chiral primary operators are sections of vector bundles, whose connection describes the operator mixing under motion on the moduli space. This connection can be exactly computed using the constraints from N = (4,4) supersymmetry. Its curvature can be determined using the tt* equations, for which we give a derivation in the physical theory which does not rely on the topological twisting. We show that for N = (4,4) theories the chiral ring is covariantly constant over the moduli space, a fact which can be seen as a non-renormalization theorem for the three-point functions of chiral primaries in AdS3/CFT2. From the spacetime point of view our analysis has the following applications. First, in the case of a D1/D5 black string, we can see the matching of the attractor flow in supergravity to RG-flow in the boundary field theory perturbed by irrelevant operators, to first order away from the fixed point. Second, under spectral flow the chiral primaries become the Ramond ground states of the CFT. These ground states represent the microstates of a small black hole in five dimensions consisting of a D1/D5 bound state. The connection that we compute can be considered as an example of Berry's phase for the internal microstates of a supersymmetric black hole.Comment: 72 pages (60 + appendices

Molecular robots guided by prescriptive landscapes

Traditional robots rely for their function on computing, to store internal representations of their goals and environment and to coordinate sensing and any actuation of components required in response. Moving robotics to the single-molecule level is possible in principle, but requires facing the limited ability of individual molecules to store complex information and programs. One strategy to overcome this problem is to use systems that can obtain complex behaviour from the interaction of simple robots with their environment. A first step in this direction was the development of DNA walkers, which have developed from being non-autonomous, to being capable of directed but brief motion on one-dimensional tracks. Here we demonstrate that previously developed random walkers—so-called molecular spiders that comprise a streptavidin molecule as an inert ‘body’ and three deoxyribozymes as catalytic ‘legs’—show elementary robotic behaviour when interacting with a precisely defined environment. Single-molecule microscopy observations confirm that such walkers achieve directional movement by sensing and modifying tracks of substrate molecules laid out on a two-dimensional DNA origami landscape. When using appropriately designed DNA origami, the molecular spiders autonomously carry out sequences of actions such as ‘start’, ‘follow’, ‘turn’ and ‘stop’. We anticipate that this strategy will result in more complex robotic behaviour at the molecular level if additional control mechanisms are incorporated. One example might be interactions between multiple molecular robots leading to collective behaviour; another might be the ability to read and transform secondary cues on the DNA origami landscape as a means of implementing Turing-universal algorithmic behaviour

Influence of history on saccade countermanding performance in humans and macaque monkeys

AbstractThe stop-signal or countermanding task probes the ability to control action by requiring subjects to withhold a planned movement in response to an infrequent stop signal which they do with variable success depending on the delay of the stop signal. We investigated whether performance of humans and macaque monkeys in a saccade countermanding task was influenced by stimulus and performance history. In spite of idiosyncrasies across subjects several trends were evident in both humans and monkeys. Response time decreased after successive trials with no stop signal. Response time increased after successive trials with a stop signal. However, post-error slowing was not observed. Increased response time was observed mainly or only after cancelled (signal inhibit) trials and not after noncancelled (signal respond) trials. These global trends were based on rapid adjustments of response time in response to momentary fluctuations in the fraction of stop signal trials. The effects of trial sequence on the probability of responding were weaker and more idiosyncratic across subjects when stop signal fraction was fixed. However, both response time and probability of responding were influenced strongly by variations in the fraction of stop signal trials. These results indicate that the race model of countermanding performance requires extension to account for these sequential dependencies and provide a basis for physiological studies of executive control of countermanding saccade performance

A supramolecular assembly mediates lentiviral DNA integration

Retroviral integrase (IN) functions within the intasome nucleoprotein complex to catalyze insertion of viral DNA into cellular chromatin. Using cryo–electron microscopy, we now visualize the functional maedi-visna lentivirus intasome at 4.9 angstrom resolution. The intasome comprises a homo-hexadecamer of IN with a tetramer-of-tetramers architecture featuring eight structurally distinct types of IN protomers supporting two catalytically competent subunits. The conserved intasomal core, previously observed in simpler retroviral systems, is formed between two IN tetramers, with a pair of C-terminal domains from flanking tetramers completing the synaptic interface. Our results explain how HIV-1 IN, which self-associates into higher-order multimers, can form a functional intasome, reconcile the bulk of early HIV-1 IN biochemical and structural data, and provide a lentiviral platform for design of HIV-1 IN inhibitors

The Resolved Properties of Extragalactic Giant Molecular Clouds

We use high spatial resolution observations of CO to systematically measure the resolved size-line width, luminosity-line width, luminosity-size, and the mass-luminosity relations of Giant Molecular Clouds (GMCs) in a variety of extragalactic systems. Although the data are heterogeneous we analyze them in a consistent manner to remove the biases introduced by limited sensitivity and resolution, thus obtaining reliable sizes, velocity dispersions, and luminosities. We compare the results obtained in dwarf galaxies with those from the Local Group spiral galaxies. We find that extragalactic GMC properties measured across a wide range of environments are very much compatible with those in the Galaxy. We use these results to investigate metallicity trends in the cloud average column density and virial CO-to-H2 factor. We find that these measurements do not accord with simple predictions from photoionization-regulated star formation theory, although this could be due to the fact that we do not sample small enough spatial scales or the full gravitational potential of the molecular cloud. We also find that the virial CO-to-H2 conversion factor in CO-bright GMCs is very similar to Galactic, and that the excursions do not show a measurable metallicity trend. We contrast these results with estimates of molecular mass based on far-infrared measurements obtained for the Small Magellanic Cloud, which systematically yield larger masses, and interpret this discrepancy as arising from large H2 envelopes that surround the CO-bright cores. We conclude that GMCs identified on the basis of their CO emission are a unique class of object that exhibit a remarkably uniform set of properties from galaxy to galaxy (abridged).Comment: 21 pages, 7 figures, 4 tables (one of them electronic). The Astrophysical Journal, accepted. Revised to reflect changes made to proof

On the concentration of large deviations for fat tailed distributions, with application to financial data

Large deviations for fat tailed distributions, i.e. those that decay slower than exponential, are not only relatively likely, but they also occur in a rather peculiar way where a finite fraction of the whole sample deviation is concentrated on a single variable. The regime of large deviations is separated from the regime of typical fluctuations by a phase transition where the symmetry between the points in the sample is spontaneously broken. For stochastic processes with a fat tailed microscopic noise, this implies that while typical realizations are well described by a diffusion process with continuous sample paths, large deviation paths are typically discontinuous. For eigenvalues of random matrices with fat tailed distributed elements, a large deviation where the trace of the matrix is anomalously large concentrates on just a single eigenvalue, whereas in the thin tailed world the large deviation affects the whole distribution. These results find a natural application to finance. Since the price dynamics of financial stocks is characterized by fat tailed increments, large fluctuations of stock prices are expected to be realized by discrete jumps. Interestingly, we find that large excursions of prices are more likely realized by continuous drifts rather than by discontinuous jumps. Indeed, auto-correlations suppress the concentration of large deviations. Financial covariance matrices also exhibit an anomalously large eigenvalue, the market mode, as compared to the prediction of random matrix theory. We show that this is explained by a large deviation with excess covariance rather than by one with excess volatility.Comment: 38 pages, 12 figure

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Short-Term Visual Deprivation Does Not Enhance Passive Tactile Spatial Acuity

An important unresolved question in sensory neuroscience is whether, and if so with what time course, tactile perception is enhanced by visual deprivation. In three experiments involving 158 normally sighted human participants, we assessed whether tactile spatial acuity improves with short-term visual deprivation over periods ranging from under 10 to over 110 minutes. We used an automated, precisely controlled two-interval forced-choice grating orientation task to assess each participant's ability to discern the orientation of square-wave gratings pressed against the stationary index finger pad of the dominant hand. A two-down one-up staircase (Experiment 1) or a Bayesian adaptive procedure (Experiments 2 and 3) was used to determine the groove width of the grating whose orientation each participant could reliably discriminate. The experiments consistently showed that tactile grating orientation discrimination does not improve with short-term visual deprivation. In fact, we found that tactile performance degraded slightly but significantly upon a brief period of visual deprivation (Experiment 1) and did not improve over periods of up to 110 minutes of deprivation (Experiments 2 and 3). The results additionally showed that grating orientation discrimination tends to improve upon repeated testing, and confirmed that women significantly outperform men on the grating orientation task. We conclude that, contrary to two recent reports but consistent with an earlier literature, passive tactile spatial acuity is not enhanced by short-term visual deprivation. Our findings have important theoretical and practical implications. On the theoretical side, the findings set limits on the time course over which neural mechanisms such as crossmodal plasticity may operate to drive sensory changes; on the practical side, the findings suggest that researchers who compare tactile acuity of blind and sighted participants should not blindfold the sighted participants