832 research outputs found
Surface immobilization of hexa-histidine-tagged adeno-associated viral vectors for localized gene delivery.
Adeno-associated viral (AAV) vectors, which are undergoing broad exploration in clinical trials, have significant promise for therapeutic gene delivery because of their safety and delivery efficiency. Gene delivery technologies capable of mediating localized gene expression may further enhance the potential of AAV in a variety of therapeutic applications by reducing spread outside a target region, which may thereby reduce off-target side effects. We have genetically engineered an AAV variant capable of binding to surfaces with high affinity through a hexa-histidine metal-binding interaction. This immobilized AAV vector system mediates high-efficiency delivery to cells that contact the surface and thus may have promise for localized gene delivery, which may aid numerous applications of AAV delivery to gene therapy
Efficient Online Timed Pattern Matching by Automata-Based Skipping
The timed pattern matching problem is an actively studied topic because of
its relevance in monitoring of real-time systems. There one is given a log
and a specification (given by a timed word and a timed automaton
in this paper), and one wishes to return the set of intervals for which the log
, when restricted to the interval, satisfies the specification
. In our previous work we presented an efficient timed pattern
matching algorithm: it adopts a skipping mechanism inspired by the classic
Boyer--Moore (BM) string matching algorithm. In this work we tackle the problem
of online timed pattern matching, towards embedded applications where it is
vital to process a vast amount of incoming data in a timely manner.
Specifically, we start with the Franek-Jennings-Smyth (FJS) string matching
algorithm---a recent variant of the BM algorithm---and extend it to timed
pattern matching. Our experiments indicate the efficiency of our FJS-type
algorithm in online and offline timed pattern matching
Guidelines on the measurement of ultraviolet radiation levels in ultraviolet phototherapy:report issued by the British Association of Dermatologists and British Photodermatology Group 2015
Photocatalytic proton reduction by a computationally identified, molecular hydrogen-bonded framework
We show that a hydrogen-bonded framework, TBAP-α, with extended Ï-stacked pyrene columns has a sacrificial photocatalytic hydrogen production rate of up to 3108 ÎŒmol g^{â1} h^{â1}. This is the highest activity reported for a molecular organic crystal. By comparison, a chemically-identical but amorphous sample of TBAP was 20â200 times less active, depending on the reaction conditions, showing unambiguously that crystal packing in molecular crystals can dictate photocatalytic activity. Crystal structure prediction (CSP) was used to predict the solid-state structure of TBAP and other functionalised, conformationally-flexible pyrene derivatives. Specifically, we show that energyâstructureâfunction (ESF) maps can be used to identify molecules such as TBAP that are likely to form extended Ï-stacked columns in the solid state. This opens up a methodology for the a priori computational design of molecular organic photocatalysts and other energy-relevant materials, such as organic electronics
Topological Surface States Protected From Backscattering by Chiral Spin Texture
Topological insulators are a new class of insulators in which a bulk gap for
electronic excitations is generated by strong spin orbit coupling. These novel
materials are distinguished from ordinary insulators by the presence of gapless
metallic boundary states, akin to the chiral edge modes in quantum Hall
systems, but with unconventional spin textures. Recently, experiments and
theoretical efforts have provided strong evidence for both two- and
three-dimensional topological insulators and their novel edge and surface
states in semiconductor quantum well structures and several Bi-based compounds.
A key characteristic of these spin-textured boundary states is their
insensitivity to spin-independent scattering, which protects them from
backscattering and localization. These chiral states are potentially useful for
spin-based electronics, in which long spin coherence is critical, and also for
quantum computing applications, where topological protection can enable
fault-tolerant information processing. Here we use a scanning tunneling
microscope (STM) to visualize the gapless surface states of the
three-dimensional topological insulator BiSb and to examine their scattering
behavior from disorder caused by random alloying in this compound. Combining
STM and angle-resolved photoemission spectroscopy, we show that despite strong
atomic scale disorder, backscattering between states of opposite momentum and
opposite spin is absent. Our observation of spin-selective scattering
demonstrates that the chiral nature of these states protects the spin of the
carriers; they therefore have the potential to be used for coherent spin
transport in spintronic devices.Comment: to be appear in Nature on August 9, 200
Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies
We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queenâs University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD
New Physics Signals in Longitudinal Gauge Boson Scattering at the LHC
We introduce a novel technique designed to look for signatures of new physics
in vector boson fusion processes at the TeV scale. This functions by measuring
the polarization of the vector bosons to determine the relative longitudinal to
transverse production. In studying this ratio we can directly probe the high
energy E^2-growth of longitudinal vector boson scattering amplitudes
characteristic of models with non-Standard Model (SM) interactions. We will
focus on studying models parameterized by an effective Lagrangian that include
a light Higgs with non-SM couplings arising from TeV scale new physics
associated with the electroweak symmetry breaking, although our technique can
be used in more general scenarios. We will show that this technique is stable
against the large uncertainties that can result from variations in the
factorization scale, improving upon previous studies that measure cross section
alone
Functional Locomotor Consequences of Uneven Forefeet for Trot Symmetry in Individual Riding Horses
ABSTRACT: Left-right symmetrical distal limb conformation can be an important prerequisite for a successful performance, and it is often hypothesized that asymmetric or uneven feet are important enhancing factors for the development of lameness. On a population level, it has been demonstrated that uneven footed horses are retiring earlier from elite level competition, but the biomechanical consequences are not yet known. The objectives of this study were to compare the functional locomotor asymmetries of horses with uneven to those with even feet. Hoof kinetics and distal limb kinematics were collected from horses (n = 34) at trot. Dorsal hoof wall angle was used to classify horses as even or uneven (1.5° difference between forefeet respectively) and individual feet as flat (55°). Functional kinetic parameters were compared between even and uneven forefeet using MANOVA followed by ANOVA. The relative influences of differences in hoof angle between the forefeet and of absolute hoof angle on functional parameters were analysed using multiple regression analysis (P<0.05). In horses with uneven feet, the side with the flatter foot showed a significantly larger maximal horizontal braking and vertical ground reaction force, a larger vertical fetlock displacement and a suppler fetlock spring. The foot with a steeper hoof angle was linearly correlated with an earlier braking-propulsion transition. The conformational differences between both forefeet were more important for loading characteristics than the individual foot conformation of each individual horse. The differences in vertical force and braking force between uneven forefeet could imply either an asymmetrical loading pattern without a pathological component or a subclinical lameness as a result of a pathological development in the steeper foot
Cosmic Flows on 100 Mpc/h Scales: Standardized Minimum Variance Bulk Flow, Shear and Octupole Moments
The low order moments, such as the bulk flow and shear, of the large scale
peculiar velocity field are sensitive probes of the matter density fluctuations
on very large scales. In practice, however, peculiar velocity surveys are
usually sparse and noisy, which can lead to the aliasing of small scale power
into what is meant to be a probe of the largest scales. Previously, we
developed an optimal ``minimum variance'' (MV) weighting scheme, designed to
overcome this problem by minimizing the difference between the measured bulk
flow (BF) and that which would be measured by an ideal survey. Here we extend
this MV analysis to include the shear and octupole moments, which are designed
to have almost no correlations between them so that they are virtually
orthogonal. We apply this MV analysis to a compilation of all major peculiar
velocity surveys, consisting of 4536 measurements. Our estimate of the BF on
scales of ~ 100 Mpc/h has a magnitude of |v|= 416 +/- 78 km/s towards Galactic
l = 282 degree +/- 11 degree and b = 6 degree +/- 6 degree. This result is in
disagreement with LCDM with WMAP5 cosmological parameters at a high confidence
level, but is in good agreement with our previous MV result without an
orthogonality constraint, showing that the shear and octupole moments did not
contaminate the previous BF measurement. The shear and octupole moments are
consistent with WMAP5 power spectrum, although the measurement noise is larger
for these moments than for the BF. The relatively low shear moments suggest
that the sources responsible for the BF are at large distances.Comment: 13 Pages, 7 figures, 4 tables. Some changes to reflect the published
versio
Strong Double Higgs Production at the LHC
The hierarchy problem and the electroweak data, together, provide a plausible
motivation for considering a light Higgs emerging as a pseudo-Goldstone boson
from a strongly-coupled sector. In that scenario, the rates for Higgs
production and decay differ significantly from those in the Standard Model.
However, one genuine strong coupling signature is the growth with energy of the
scattering amplitudes among the Goldstone bosons, the longitudinally polarized
vector bosons as well as the Higgs boson itself. The rate for double Higgs
production in vector boson fusion is thus enhanced with respect to its
negligible rate in the SM. We study that reaction in pp collisions, where the
production of two Higgs bosons at high pT is associated with the emission of
two forward jets. We concentrate on the decay mode hh -> WW^(*)WW^(*) and study
the semi-leptonic decay chains of the W's with 2, 3 or 4 leptons in the final
states. While the 3 lepton final states are the most relevant and can lead to a
3 sigma signal significance with 300 fb^{-1} collected at a 14 TeV LHC, the two
same-sign lepton final states provide complementary information. We also
comment on the prospects for improving the detectability of double Higgs
production at the foreseen LHC energy and luminosity upgrades.Comment: 54 pages, 26 figures. v2: typos corrected, a few comments and one
table added. Version published in JHE
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