994 research outputs found
Nanopore sensing at ultra-low concentrations using single molecule dielectrophoretic trapping
Single-molecule techniques are being developed with the exciting prospect of revolutionizing the healthcare industry by generating vast amounts of genetic and proteomic data. One exceptionally promising route is in the use of nanopore sensors. However, a well-known complexity is that detection and capture is predominantly diffusion limited. This problem is compounded when taking into account the capture volume of a nanopore, typically 108–1010 times smaller than the sample volume. To rectify this disproportionate ratio, we demonstrate a simple, yet powerful, method based on coupling single-molecule dielectrophoretic trapping to nanopore sensing. We show that DNA can be captured from a controllable, but typically much larger, volume and concentrated at the tip of a metallic nanopore. This enables the detection of single molecules at concentrations as low as 5 fM, which is approximately a 103 reduction in the limit of detection compared with existing methods, while still maintaining efficient throughput
Supersymmetric Charged Clouds in AdS_5
We consider supersymmetric holographic flows that involve background gauge
fields dual to chemical potentials in the boundary field theory. We use a
consistent truncation of gauged N=8 supergravity in five dimensions and we give
a complete analysis of the supersymmetry conditions for a large family of
flows. We examine how the well-known supersymmetric flow between two fixed
points is modified by the presence of the chemical potentials and this yields a
new, completely smooth, solution that interpolates between two global AdS
spaces of different radii and with different values of the chemical potential.
We also examine some black-hole-like singular flows and a new
non-supersymmetric black hole solution. We comment on the interpretation of our
new solutions in terms of giant gravitons and discuss the implications of our
work for finding black-hole solutions in AdS geometries.Comment: 31 pages, 6 figures; minor corrections, updated reference
Wilsonian Approach to Fluid/Gravity Duality
The problem of gravitational fluctuations confined inside a finite cutoff at
radius outside the horizon in a general class of black hole geometries
is considered. Consistent boundary conditions at both the cutoff surface and
the horizon are found and the resulting modes analyzed. For general cutoff
the dispersion relation is shown at long wavelengths to be that of a
linearized Navier-Stokes fluid living on the cutoff surface. A cutoff-dependent
line-integral formula for the diffusion constant is derived. The
dependence on is interpreted as renormalization group (RG) flow in the
fluid. Taking the cutoff to infinity in an asymptotically AdS context, the
formula for reproduces as a special case well-known results derived
using AdS/CFT. Taking the cutoff to the horizon, the effective speed of sound
goes to infinity, the fluid becomes incompressible and the Navier-Stokes
dispersion relation becomes exact. The resulting universal formula for the
diffusion constant reproduces old results from the membrane
paradigm. Hence the old membrane paradigm results and new AdS/CFT results are
related by RG flow. RG flow-invariance of the viscosity to entropy ratio is shown to follow from the first law of thermodynamics together with
isentropy of radial evolution in classical gravity. The ratio is expected to
run when quantum gravitational corrections are included.Comment: 34 pages, harvmac, clarified boundary conditio
Q methodology and a Delphi poll: a useful approach to researching a narrative approach to therapy
Q methodology and a Delphi poll combined qualitative and quantitative methods to explore definitions of White and Epston's (1990) narrative approach to therapy among a group of UK practitioners. A Delphi poll was used to generate statements about narrative therapy. The piloting of statements by the Delphi panel identified agreement about theoretical ideas underpinning narrative therapy and certain key practices. A wider group of practitioners ranked the statements in a Q sort and made qualitative comments about their sorting. Quantitative methods (principal components analysis) were used to extract eight accounts of narrative therapy, five of which are qualitatively analysed in this paper. Agreement and differences were identified across a range of issues, including the social construction of narratives, privileging a political stance or narrative techniques and the relationship with other therapies, specifically systemic psychotherapy. Q methodology, combined with the Delphi poll, was a unique and innovative feature of this study
Differential Effects of MYH9 and APOL1 Risk Variants on FRMD3 Association with Diabetic ESRD in African Americans
Single nucleotide polymorphisms (SNPs) in MYH9 and APOL1 on chromosome 22 (c22) are powerfully associated with non-diabetic end-stage renal disease (ESRD) in African Americans (AAs). Many AAs diagnosed with type 2 diabetic nephropathy (T2DN) have non-diabetic kidney disease, potentially masking detection of DN genes. Therefore, genome-wide association analyses were performed using the Affymetrix SNP Array 6.0 in 966 AA with T2DN and 1,032 non-diabetic, non-nephropathy (NDNN) controls, with and without adjustment for c22 nephropathy risk variants. No associations were seen between FRMD3 SNPs and T2DN before adjusting for c22 variants. However, logistic regression analysis revealed seven FRMD3 SNPs significantly interacting with MYH9—a finding replicated in 640 additional AA T2DN cases and 683 NDNN controls. Contrasting all 1,592 T2DN cases with all 1,671 NDNN controls, FRMD3 SNPs appeared to interact with the MYH9 E1 haplotype (e.g., rs942280 interaction p-value = 9.3E−7 additive; odds ratio [OR] 0.67). FRMD3 alleles were associated with increased risk of T2DN only in subjects lacking two MYH9 E1 risk haplotypes (rs942280 OR = 1.28), not in MYH9 E1 risk allele homozygotes (rs942280 OR = 0.80; homogeneity p-value = 4.3E−4). Effects were weaker stratifying on APOL1. FRMD3 SNPS were associated with T2DN, not type 2 diabetes per se, comparing AAs with T2DN to those with diabetes lacking nephropathy. T2DN-associated FRMD3 SNPs were detectable in AAs only after accounting for MYH9, with differential effects for APOL1. These analyses reveal a role for FRMD3 in AA T2DN susceptibility and accounting for c22 nephropathy risk variants can assist in detecting DN susceptibility genes
Preliminary Report: Missense mutations in the APOL gene family are associated with end stage kidney disease risk previously attributed to the MYH9 gene
MYH9 has been proposed as a major genetic risk locus for a spectrum of
non-diabetic end stage kidney disease (ESKD). We use recently released
sequences from the 1000 Genomes Project to identify two western African
specific missense mutations (S342G and I384M) in the neighbouring APOL1 gene,
and demonstrate that these are more strongly associated with ESKD than
previously reported MYH9 variants. We also show that the distribution of these
risk variants in African populations is consistent with the pattern of African
ancestry ESKD risk previously attributed to the MYH9 gene. Additional
associations were also found among other members of the APOL gene family, and
we propose that ESKD risk is caused by western African variants in members of
the APOL gene family, which evolved to confer protection against pathogens,
such as Trypanosoma.Comment: 25 pages, 6 figure
Distances from Surface Brightness Fluctuations
The practice of measuring galaxy distances from their spatial fluctuations in
surface brightness is now a decade old. While several past articles have
included some review material, this is the first intended as a comprehensive
review of the surface brightness fluctuation (SBF) method. The method is
conceptually quite simple, the basic idea being that nearby (but unresolved)
star clusters and galaxies appear "bumpy", while more distant ones appear
smooth. This is quantified via a measurement of the amplitude of the Poisson
fluctuations in the number of unresolved stars encompassed by a CCD pixel
(usually in an image of an elliptical galaxy). Here, we describe the technical
details and difficulties involved in making SBF measurements, discuss
theoretical and empirical calibrations of the method, and review the numerous
applications of the method from the ground and space, in the optical and
near-infrared. We include discussions of stellar population effects and the
"universality" of the SBF standard candle. A final section considers the future
of the method.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles',
A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 22
pages, including 3 postscript figures; uses Kluwer's crckapb.sty LaTex macro
file, enclose
Holographic renormalization and supersymmetry
Holographic renormalization is a systematic procedure for regulating
divergences in observables in asymptotically locally AdS spacetimes. For dual
boundary field theories which are supersymmetric it is natural to ask whether
this defines a supersymmetric renormalization scheme. Recent results in
localization have brought this question into sharp focus: rigid supersymmetry
on a curved boundary requires specific geometric structures, and general
arguments imply that BPS observables, such as the partition function, are
invariant under certain deformations of these structures. One can then ask if
the dual holographic observables are similarly invariant. We study this
question in minimal N = 2 gauged supergravity in four and five dimensions. In
four dimensions we show that holographic renormalization precisely reproduces
the expected field theory results. In five dimensions we find that no choice of
standard holographic counterterms is compatible with supersymmetry, which leads
us to introduce novel finite boundary terms. For a class of solutions
satisfying certain topological assumptions we provide some independent tests of
these new boundary terms, in particular showing that they reproduce the
expected VEVs of conserved charges.Comment: 70 pages; corrected typo
A frequentist framework of inductive reasoning
Reacting against the limitation of statistics to decision procedures, R. A.
Fisher proposed for inductive reasoning the use of the fiducial distribution, a
parameter-space distribution of epistemological probability transferred
directly from limiting relative frequencies rather than computed according to
the Bayes update rule. The proposal is developed as follows using the
confidence measure of a scalar parameter of interest. (With the restriction to
one-dimensional parameter space, a confidence measure is essentially a fiducial
probability distribution free of complications involving ancillary statistics.)
A betting game establishes a sense in which confidence measures are the only
reliable inferential probability distributions. The equality between the
probabilities encoded in a confidence measure and the coverage rates of the
corresponding confidence intervals ensures that the measure's rule for
assigning confidence levels to hypotheses is uniquely minimax in the game.
Although a confidence measure can be computed without any prior distribution,
previous knowledge can be incorporated into confidence-based reasoning. To
adjust a p-value or confidence interval for prior information, the confidence
measure from the observed data can be combined with one or more independent
confidence measures representing previous agent opinion. (The former confidence
measure may correspond to a posterior distribution with frequentist matching of
coverage probabilities.) The representation of subjective knowledge in terms of
confidence measures rather than prior probability distributions preserves
approximate frequentist validity.Comment: major revisio
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