Minimum requirements for feedback enhanced force sensing

The problem of estimating an unknown force driving a linear oscillator is revisited. When using linear measurement, feedback is often cited as a mechanism to enhance bandwidth or sensitivity. We show that as long as the oscillator dynamics are known, there exists a real-time estimation strategy that reproduces the same measurement record as any arbitrary feedback protocol. Consequently some form of nonlinearity is required to gain any advantage beyond estimation alone. This result holds true in both quantum and classical systems, with non-stationary forces and feedback, and in the general case of non-Gaussian and correlated noise. Recently, feedback enhanced incoherent force sensing has been demonstrated [Nat. Nano. \textbf{7}, 509 (2012)], with the enhancement attributed to a feedback induced modification of the mechanical susceptibility. As a proof-of-principle we experimentally reproduce this result through straightforward filtering.Comment: 5 pages + 2 pages of Supplementary Informatio

Descendents of Edward Melcher, a Baker of Portsmouth, NH in 1657

Alt title : Descendants of Edward Melcher, a Baker of Portsmouth, NH in 1657https://digitalmaine.com/books/1153/thumbnail.jp

Melcher in New England : 1657-1973 (1992 Edition)

https://digitalmaine.com/books/1152/thumbnail.jp

Melcher in New England : 1657-1973 (1989 Edition)

https://digitalmaine.com/books/1154/thumbnail.jp

The kinetics of the reaction of superoxide radical with Fe(III) complexes of EDTA, DETAPAC and HEDTA

AbstractTo gain an understanding of the mechanism by which the hydroxyl free radical can arise in superoxide generating systems and learn how different chelaters of iron can inhibit this reaction, a pulse radiolysis kinetic study of the reaction of O−2 with Fe(III)EDTA, Fe(III)HEDTA and Fe(III)DETAPAC (or DTPA) was undertaken. Superoxide reacts readily with Fe(III)EDTA and Fe(III)HEDTA with a pH-dependent second-order rate constant having values of 1.9 × 106 M−1.s−1 and 7.6 × 105 M−1.s−1 at pH 7, respectively. However, the rate constant for the reaction of O−2 with Fe(III)DETAPAC was found to be much slower, the upper limit for the rate constant being 104 M−1.s−1. These results in conjunction with spin-trapping experiments with Fe(II)EDTA, Fe(II)HEDTA, Fe(II)DETAPAC and H2O2 suggests that DETAPAC inhibits the formation of OH by slowing the reduction of Fe(III) to Fe(II) and not by inhibiting the Fenton reaction

Artificial intelligence for dementia drug discovery and trials optimization

Drug discovery and clinical trial design for dementia have historically been challenging. In part these challenges have arisen from patient heterogeneity, length of disease course, and the tractability of a target for the brain. Applying big data analytics and machine learning tools for drug discovery and utilizing them to inform successful clinical trial design has the potential to accelerate progress. Opportunities arise at multiple stages in the therapy pipeline and the growing availability of large medical data sets opens possibilities for big data analyses to answer key questions in clinical and therapeutic challenges. However, before this goal is reached, several challenges need to be overcome and only a multi‐disciplinary approach can promote data‐driven decision‐making to its full potential. Herein we review the current state of machine learning applications to clinical trial design and drug discovery, while presenting opportunities and recommendations that can break down the barriers to implementation

High Prevalence of the Amphibian Chytrid Fungus (\u3cem\u3eBatrachochytrium dendrobatidis\u3c/em\u3e) across Multiple Taxa and Localities in the Highlands of Ethiopia

Surveys of the potentially lethal amphibian chytrid fungus (Batrachochytrium dendrobatidis - Bd) in Africa are patchy, especially in some regions of high species endemicity. We present results of the first Bd surveys of wild amphibians in Ethiopia, for two upland regions on either side of the Rift Valley: the Bale Mountains and the Kaffa region. Surveys were opportunistic so that robust interpretation of the data is limited. Utilizing diagnostic qPCR assays, 51 out of 120 frogs (14 species in 10 genera) tested positive for Bd at altitudes of 1,620–3,225 m, across all genera and species, and all but two localities. Prevalence was not significantly different between the two regions or two years (2008, 2009) sampled. Prevalence and parasite load was higher in species with aquatic tadpoles than those with terrestrial early life-history stages, but these differences were not significant. Impacts of Bd infection were not investigated, but no dead or dying frogs were found. This is the first report of Bd in Ethiopia, a country in which approximately 40% of its more than 60 species are endemic. Declines have occurred in some frog species in some localities in Ethiopia, and although habitat degradation is a likely cause in at least some places, further studies of Bd in Ethiopia are required to understand if it is a threat

The outer halos of elliptical galaxies

Recent progress is summarized on the determination of the density distributions of stars and dark matter, stellar kinematics, and stellar population properties, in the extended, low surface brightness halo regions of elliptical galaxies. With integral field absorption spectroscopy and with planetary nebulae as tracers, velocity dispersion and rotation profiles have been followed to ~4 and ~5-8 effective radii, respectively, and in M87 to the outer edge at ~150 kpc. The results are generally consistent with the known dichotomy of elliptical galaxy types, but some galaxies show more complex rotation profiles in their halos and there is a higher incidence of misalignments, indicating triaxiality. Dynamical models have shown a range of slopes for the total mass profiles, and that the inner dark matter densities in ellipticals are higher than in spiral galaxies, indicating earlier assembly redshifts. Analysis of the hot X-ray emitting gas in X-ray bright ellipticals and comparison with dynamical mass determinations indicates that non-thermal components to the pressure may be important in the inner ~10 kpc, and that the properties of these systems are closely related to their group environments. First results on the outer halo stellar population properties do not yet give a clear picture. In the halo of one bright galaxy, lower [alpha/Fe] abundances indicate longer star formation histories pointing towards late accretion of the halo. This is consistent with independent evidence for on-going accretion, and suggests a connection to the observed size evolution of elliptical galaxies with redshift.Comment: 8 pages. Invited review to appear in the proceedings of "Galaxies and their Masks" eds. Block, D.L., Freeman, K.C. & Puerari, I., 2010, Springer (New York

Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins

PrimPol is a recently identified polymerase involved in eukaryotic DNA damage tolerance, employed in both re-priming and translesion synthesis mechanisms to bypass nuclear and mitochondrial DNA lesions. In this report, we investigate how the enzymatic activities of human PrimPol are regulated. We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and does not interact with it in vivo. We identify that PrimPol interacts with both of the major single-strand binding proteins, RPA and mtSSB in vivo. Using NMR spectroscopy, we characterize the domains responsible for the PrimPol-RPA interaction, revealing that PrimPol binds directly to the N-terminal domain of RPA70. In contrast to the established role of SSBs in stimulating replicative polymerases, we find that SSBs significantly limit the primase and polymerase activities of PrimPol. To identify the requirement for this regulation, we employed two forward mutation assays to characterize PrimPol's replication fidelity. We find that PrimPol is a mutagenic polymerase, with a unique error specificity that is highly biased towards insertion-deletion errors. Given the error-prone disposition of PrimPol, we propose a mechanism whereby SSBs greatly restrict the contribution of this enzyme to DNA replication at stalled forks, thus reducing the mutagenic potential of PrimPol during genome replication

Scalable context-dependent analysis of emergency egress models

Pervasive environments offer an increasing number of services to a large number of people moving within these environments, including timely information about where to go and when, and contextual information about the surrounding environment. This information may be conveyed to people through public displays or direct to a person's mobile phone. People using these services interact with the system but they are also meeting other people and performing other activities as relevant opportunities arise. The design of such systems and the analysis of collective dynamic behaviour of people within them is a challenging problem. We present results on a novel usage of a scalable analysis technique in this context. We show the validity of an approach based on stochastic process-algebraic models by focussing on a representative example, i.e. emergency egress. The chosen case study has the advantage that detailed data is available from studies employing alternative analysis methods, making cross-methodology comparison possible. We also illustrate how realistic, context-dependent human behaviour, often observed in emergency egress, can naturally be embedded in the models, and how the effect of such behaviour on evacuation can be analysed in an efficient and scalable way. The proposed approach encompasses both the agent modelling viewpoint, as system behaviour emerges from specific (discrete) agent interaction, and the population viewpoint, when classes of homogeneous individuals are considered for a (continuous)approximation of overall system behaviour