18,428 research outputs found
Low-background temperature sensors fabricated on parylene substrates
Temperature sensors fabricated from ultra-low radioactivity materials have
been developed for low-background experiments searching for neutrinoless
double-beta decay and the interactions of WIMP dark matter. The sensors consist
of electrical traces photolithographically-patterned onto substrates of
vapor-deposited parylene. They are demonstrated to function as expected, to do
so reliably and robustly, and to be highly radio-pure. This work is a
proof-of-concept study of a technology that can be applied to broad class of
electronic circuits used in low-background experiments
ATP-Stimulated, DNA-Mediated Redox Signaling by XPD, a DNA Repair and Transcription Helicase
Using DNA-modified electrodes, we show DNA-mediated signaling by XPD, a helicase that contains a [4Fe-4S] cluster and is critical for nucleotide excision repair and transcription. The DNA-mediated redox signal resembles that of base excision repair proteins, with a DNA-bound redox potential of ~80 mV versus NHE. Significantly, this signal increases with ATP hydrolysis. Moreover, the redox signal is substrate-dependent, reports on the DNA conformational changes associated with enzymatic function, and may reflect a general biological role for DNA charge transport
Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape.
Vaccination has essentially eradicated poliovirus. Yet, its mutation rate is higher than that of viruses like HIV, for which no effective vaccine exists. To investigate this, we infer a fitness model for the poliovirus viral protein 1 (vp1), which successfully predicts in vitro fitness measurements. This is achieved by first developing a probabilistic model for the prevalence of vp1 sequences that enables us to isolate and remove data that are subject to strong vaccine-derived biases. The intrinsic fitness constraints derived for vp1, a capsid protein subject to antibody responses, are compared with those of analogous HIV proteins. We find that vp1 evolution is subject to tighter constraints, limiting its ability to evade vaccine-induced immune responses. Our analysis also indicates that circulating poliovirus strains in unimmunized populations serve as a reservoir that can seed outbreaks in spatio-temporally localized sub-optimally immunized populations
A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis
© Queen’s Printer and Controller of HMSO 2013Severe allergic rhinitis uncontrolled by conventional medication can substantially affect quality of life. Immunotherapy involves administering increasing doses of a specific allergen, with the aim of reducing sensitivity and symptomatic reactions. Recent meta-analyses have concluded that both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are more effective than placebo in reducing symptoms. It is uncertain which route of administration is more effective and whether or not treatment is cost-effective.National Institute for Health Research Health Technology Assessment programm
DNA charge transport as a first step in coordinating the detection of lesions by repair proteins
Damaged bases in DNA are known to lead to errors in replication and transcription, compromising the integrity of the genome. We have proposed a model where repair proteins containing redox-active [4Fe-4S] clusters utilize DNA charge transport (CT) as a first step in finding lesions. In this model, the population of sites to search is reduced by a localization of protein in the vicinity of lesions. Here, we examine this model using single-molecule atomic force microscopy (AFM). XPD, a 5′-3′ helicase involved in nucleotide excision repair, contains a [4Fe-4S] cluster and exhibits a DNA-bound redox potential that is physiologically relevant. In AFM studies, we observe the redistribution of XPD onto kilobase DNA strands containing a single base mismatch, which is not a specific substrate for XPD but, like a lesion, inhibits CT. We further provide evidence for DNA-mediated signaling between XPD and Endonuclease III (EndoIII), a base excision repair glycosylase that also contains a [4Fe-4S] cluster. When XPD and EndoIII are mixed together, they coordinate in relocalizing onto the mismatched strand. However, when a CT-deficient mutant of either repair protein is combined with the CT-proficient repair partner, no relocalization occurs. These data not only indicate a general link between the ability of a repair protein to carry out DNA CT and its ability to redistribute onto DNA strands near lesions but also provide evidence for coordinated DNA CT between different repair proteins in their search for damage in the genome
Search for correlation effects in linear chains of trapped ions
We report a precise search for correlation effects in linear chains of 2 and
3 trapped Ca+ ions. Unexplained correlations in photon emission times within a
linear chain of trapped ions have been reported, which, if genuine, cast doubt
on the potential of an ion trap to realize quantum information processing. We
observe quantum jumps from the metastable 3d 2D_{5/2} level for several hours,
searching for correlations between the decay times of the different ions. We
find no evidence for correlations: the number of quantum jumps with separations
of less than 10 ms is consistent with statistics to within errors of 0.05%; the
lifetime of the metastable level derived from the data is consistent with that
derived from independent single-ion data at the level of the experimental
errors 1%; and no rank correlations between the decay times were found with
sensitivity to rank correlation coefficients at the level of |R| = 0.024.Comment: With changes to introduction. 5 pages, including 4 figures. Submitted
to Europhys. Let
Moving Mirrors and Thermodynamic Paradoxes
Quantum fields responding to "moving mirrors" have been predicted to give
rise to thermodynamic paradoxes. I show that the assumption in such work that
the mirror can be treated as an external field is invalid: the exotic
energy-transfer effects necessary to the paradoxes are well below the scales at
which the model is credible. For a first-quantized point-particle mirror, it
appears that exotic energy-transfers are lost in the quantum uncertainty in the
mirror's state. An accurate accounting of these energies will require a model
which recognizes the mirror's finite reflectivity, and almost certainly a model
which allows for the excitation of internal mirror modes, that is, a
second-quantized model.Comment: 7 pages, Revtex with Latex2
Plastic-crystalline solid-state electrolytes: Ionic conductivity and orientational dynamics in nitrile mixtures
Many plastic crystals, molecular solids with long-range, center-of-mass
crystalline order but dynamic disorder of the molecular orientations, are known
to exhibit exceptionally high ionic conductivity. This makes them promising
candidates for applications as solid-state electrolytes, e.g., in batteries.
Interestingly, it was found that the mixing of two different
plastic-crystalline materials can considerably enhance the ionic dc
conductivity, an important benchmark quantity for electrochemical applications.
An example is the admixture of different nitriles to succinonitrile, the latter
being one of the most prominent plastic-crystalline ionic conductors. However,
until now only few such mixtures were studied. In the present work, we
investigate succinonitrile mixed with malononitrile, adiponitrile, and
pimelonitrile, to which 1 mol% of Li ions were added. Using differential
scanning calorimetry and dielectric spectroscopy, we examine the phase behavior
and the dipolar and ionic dynamics of these systems. We especially address the
mixing-induced enhancement of the ionic conductivity and the coupling of the
translational ionic mobility to the molecular reorientational dynamics,
probably arising via a "revolving-door" mechanism.Comment: 9 pages, 7 figures; revised version as accepted for publication in J.
Chem. Phy
Optimal Computation of Avoided Words
The deviation of the observed frequency of a word from its expected
frequency in a given sequence is used to determine whether or not the word
is avoided. This concept is particularly useful in DNA linguistic analysis. The
value of the standard deviation of , denoted by , effectively
characterises the extent of a word by its edge contrast in the context in which
it occurs. A word of length is a -avoided word in if
, for a given threshold . Notice that such a word
may be completely absent from . Hence computing all such words na\"{\i}vely
can be a very time-consuming procedure, in particular for large . In this
article, we propose an -time and -space algorithm to compute all
-avoided words of length in a given sequence of length over a
fixed-sized alphabet. We also present a time-optimal -time and
-space algorithm to compute all -avoided words (of any
length) in a sequence of length over an alphabet of size .
Furthermore, we provide a tight asymptotic upper bound for the number of
-avoided words and the expected length of the longest one. We make
available an open-source implementation of our algorithm. Experimental results,
using both real and synthetic data, show the efficiency of our implementation
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