3,448 research outputs found
RDX Induces Aberrant Expression of MicroRNAs in Mouse Brain and Liver
Background: Although microRNAs (miRNAs) have been found to play an important role in many biological and metabolic processes, their functions in animal response to environmental toxicant exposure are largely unknown.
Objectives: We used hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a common environmental contaminant, as a toxicant stressor to investigate toxicant-induced changes in miRNA expression in B6C3F1 mice and the potential mechanism of RDX-induced toxic action.
Methods: B6C3F1 mice were fed diets with or without 5 mg/kg RDX for 28 days. After the feeding trials, we isolated RNAs from both brain and liver tissues and analyzed the expression profiles of 567 known mouse miRNAs using microarray and quantitative real-time polymerase chain reaction technologies.
Results: RDX exposure induced significant changes in miRNA expression profiles. A total of 113 miRNAs, belonging to 75 families, showed significantly altered expression patterns after RDX exposure. Of the 113 miRNAs, 10 were significantly up-regulated and 3 were significantly down-regulated (p < 0.01) in both mouse brain and liver. Many miRNAs had tissue-specific responses to RDX exposure. Specifically, expression of seven miRNAs was up-regulated in the brain but down-regulated in the liver or up-regulated in the liver but down-regulated in the brain (p < 0.01). Many aberrantly expressed miRNAs were related to various cancers, toxicant-metabolizing enzymes, and neurotoxicity. We found a significant up-regulation of oncogenic miRNAs and a significant down-regulation of tumor-suppressing miRNAs, which included let-7, miR-17-92, miR-10b, miR-15, miR-16, miR-26, and miR-181.
Conclusions: Environmental toxicant exposure alters the expression of a suite of miRNAs. Originally published Environmental Health Perspectives, Vol. 117, No. 2, Feb 200
Kinetic Analysis of Discrete Path Sampling Stationary Point Databases
Analysing stationary point databases to extract phenomenological rate
constants can become time-consuming for systems with large potential energy
barriers. In the present contribution we analyse several different approaches
to this problem. First, we show how the original rate constant prescription
within the discrete path sampling approach can be rewritten in terms of
committor probabilities. Two alternative formulations are then derived in which
the steady-state assumption for intervening minima is removed, providing both a
more accurate kinetic analysis, and a measure of whether a two-state
description is appropriate. The first approach involves running additional
short kinetic Monte Carlo (KMC) trajectories, which are used to calculate
waiting times. Here we introduce `leapfrog' moves to second-neighbour minima,
which prevent the KMC trajectory oscillating between structures separated by
low barriers. In the second approach we successively remove minima from the
intervening set, renormalising the branching probabilities and waiting times to
preserve the mean first-passage times of interest. Regrouping the local minima
appropriately is also shown to speed up the kinetic analysis dramatically at
low temperatures. Applications are described where rates are extracted for
databases containing tens of thousands of stationary points, with effective
barriers that are several hundred times kT.Comment: 28 pages, 1 figure, 4 table
Group Leaders Optimization Algorithm
We present a new global optimization algorithm in which the influence of the
leaders in social groups is used as an inspiration for the evolutionary
technique which is designed into a group architecture. To demonstrate the
efficiency of the method, a standard suite of single and multidimensional
optimization functions along with the energies and the geometric structures of
Lennard-Jones clusters are given as well as the application of the algorithm on
quantum circuit design problems. We show that as an improvement over previous
methods, the algorithm scales as N^2.5 for the Lennard-Jones clusters of
N-particles. In addition, an efficient circuit design is shown for two qubit
Grover search algorithm which is a quantum algorithm providing quadratic
speed-up over the classical counterpart
Incidence of malignant neoplasms among HIV-infected persons in Scotland
Among 2574 persons diagnosed with HIV throughout Scotland and observed over the period 1981-1996, cancer incidence compared to the general population was 11 times higher overall; among homosexual/bisexual males, it was 21 times higher and among injecting drug users, haemophiliacs and heterosexuals it was five times higher, mostly due to AIDS-defining neoplasms. However, liver, lung and skin cancers (all non-AIDS-defining) were also significantly increased
Nanomechanics of graphene oxide-bacteriophage based self-assembled porous composites.
Graphene oxide, integrated with the filamentous bacteriophage M13, forms a 3D large-scale multifunctional porous structure by self-assembly, with considerable potential for applications. We performed Raman spectroscopy under pressure on this porous composite to understand its fundamental mechanics. The results show that at low applied pressure, the [Formula: see text] bonds of graphene oxide stiffen very little with increasing pressure, suggesting a complicated behaviour of water intercalated between the graphene layers. The key message of this paper is that water in a confined space can have a significant impact on the nanostructure that hosts it. We introduced carbon nanotubes during the self-assembly of graphene oxide and M13, and a similar porous macro-structure was observed. However, in the presence of carbon nanotubes, pressure is transmitted to the [Formula: see text] bonds of graphene oxide straightforwardly as in graphite. The electrical conductivity of the composite containing carbon nanotubes is improved by about 30 times at a bias voltage of 10 V. This observation suggests that the porous structure has potential in applications where good electrical conductivity is desired, such as sensors and batteries
Analyticity, Unitarity and One-loop Graviton Corrections to Compton Scattering
We compute spin-flip cross section for graviton photoproduction on a spin-1/2
target of finite mass. Using this tree-level result, we find one-loop graviton
correction to the spin-flip low-energy forward Compton scattering amplitude by
using Gerasimov-Drell-Hearn sum rule. We show that this result agrees with the
corresponding perturbative computations, implying the validity of the sum rule
at one-loop level, contrary to the previous claims. We discuss possible effects
from the black hole production and string Regge trajectory exchange at very
high energies. These effects seem to soften the UV divergence present at
one-loop graviton level. Finally, we discuss the relation of these observations
with the models that involve extra dimensions.Comment: 15 pages, 3 figure
Reasons for and consequences of missed appointments in general practice in the UK: questionnaire survey and prospective review of medical records
Background
Missed appointments are a common occurrence in primary care in the UK, yet little is known about the reasons for them, or the consequences of missing an appointment. This paper aims to determine the reasons for missed appointments and whether patients who miss an appointment subsequently consult their general practitioner (GP). Secondary aims are to compare psychological morbidity, and the previous appointments with GPs between subjects and a comparison group.
Methods
Postal questionnaire survey and prospective medical notes review of adult patients missing an appointment and the comparison group who attended appointments over a three week period in seven general practices in West Yorkshire.
Results
Of the 386 who missed appointments 122 (32%) responded. Of the 386 in the comparison group 223 (58%) responded, resulting in 23 case-control matched pairs with complete data collection. Over 40% of individuals who missed an appointment and participated said that they forgot the appointment and a quarter said that they tried very hard to cancel the appointment or that it was at an inconvenient time. A fifth reported family commitments or being too ill to attend. Over 90% of the patients who missed an appointment subsequently consulted within three months and of these nearly 60% consulted for the stated problem that was going to be presented in the missed consultation. The odds of missing an appointment decreased with increasing age and were greater among those who had missed at least one appointment in the previous 12 months. However, estimates for comparisons between those who missed appointments and the comparison group were imprecise due to the low response rate.
Conclusion
Patients who miss appointments tend to cite practice factors and their own forgetfulness as the main reasons for doing so, and most attend within three months of a missed appointment. This study highlights a number of implications for future research. More work needs to be done to engage people who miss appointments into research in a meaningful way
"Summary Page": a novel tool that reduces omitted data in research databases
<p>Abstract</p> <p>Background</p> <p>Data entry errors are common in clinical research databases. Omitted data are of particular concern because they are more common than erroneously inserted data and therefore could potentially affect research findings. However, few affordable strategies for their prevention are available.</p> <p>Methods</p> <p>We have conducted a prospective observational study of the effect of a novel tool called "<it>Summary Page</it>" on the frequency of correction of omitted data errors in a radiation oncology research database between July 2008 and March 2009. "<it>Summary Page</it>" was implemented as an optionally accessed screen in the database that visually integrates key fields in the record. We assessed the frequency of omitted data on the example of the <it>Date of Relapse </it>field. We considered the data in this field to be omitted for all records that had empty <it>Date of Relapse </it>field and evidence of relapse elsewhere in the record.</p> <p>Results</p> <p>A total of 1,156 records were updated and 200 new records were entered in the database over the study period. "<it>Summary Page</it>" was accessed for 44% of all updated records and for 69% of newly entered records. Frequency of correction of the omitted date of cancer relapse was six-fold higher in records for which "<it>Summary Page</it>" was accessed (p = 0.0003).</p> <p>Conclusions</p> <p>"<it>Summary Page</it>" was strongly associated with an increased frequency of correction of omitted data errors. Further, controlled, studies are needed to confirm this finding and elucidate its mechanism of action.</p
- …