1,678 research outputs found
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Kelch proteins: emerging roles in skeletal muscle development and diseases
Our understanding of genes that cause skeletal muscle disease has increased tremendously over the past three decades. Advances in approaches to genetics and genomics have aided in the identification of new pathogenic mechanisms in rare genetic disorders and have opened up new avenues for therapeutic interventions by identification of new molecular pathways in muscle disease. Recent studies have identified mutations of several Kelch proteins in skeletal muscle disorders. The Kelch superfamily is one of the largest evolutionary conserved gene families. The 66 known family members all possess a Kelch-repeat containing domain and are implicated in diverse biological functions. In skeletal muscle development, several Kelch family members regulate the processes of proliferation and/or differentiation resulting in normal functioning of mature muscles. Importantly, many Kelch proteins function as substrate-specific adaptors for Cullin E3 ubiquitin ligase (Cul3), a core component of the ubiquitin-proteasome system to regulate the protein turnover. This review discusses the emerging roles of Kelch proteins in skeletal muscle function and disease
Finite difference time domain modeling of steady state scattering from jet engines with moving turbine blades
The approach chosen to model steady state scattering from jet engines with moving turbine blades is based upon the Finite Difference Time Domain (FDTD) method. The FDTD method is a numerical electromagnetic program based upon the direct solution in the time domain of Maxwell's time dependent curl equations throughout a volume. One of the strengths of this method is the ability to model objects with complicated shape and/or material composition. General time domain functions may be used as source excitations. For example, a plane wave excitation may be specified as a pulse containing many frequencies and at any incidence angle to the scatterer. A best fit to the scatterer is accomplished using cubical cells in the standard cartesian implementation of the FDTD method. The material composition of the scatterer is determined by specifying its electrical properties at each cell on the scatterer. Thus, the FDTD method is a suitable choice for problems with complex geometries evaluated at multiple frequencies. It is assumed that the reader is familiar with the FDTD method
Periodic Neural Activity Induced by Network Complexity
We study a model for neural activity on the small-world topology of Watts and
Strogatz and on the scale-free topology of Barab\'asi and Albert. We find that
the topology of the network connections may spontaneously induce periodic
neural activity, contrasting with chaotic neural activities exhibited by
regular topologies. Periodic activity exists only for relatively small networks
and occurs with higher probability when the rewiring probability is larger. The
average length of the periods increases with the square root of the network
size.Comment: 4 pages, 5 figure
Scaling law for the transient behavior of type-II neuron models
We study the transient regime of type-II biophysical neuron models and
determine the scaling behavior of relaxation times near but below the
repetitive firing critical current, . For both
the Hodgkin-Huxley and Morris-Lecar models we find that the critical exponent
is independent of the numerical integration time step and that both systems
belong to the same universality class, with . For appropriately
chosen parameters, the FitzHugh-Nagumo model presents the same generic
transient behavior, but the critical region is significantly smaller. We
propose an experiment that may reveal nontrivial critical exponents in the
squid axon.Comment: 6 pages, 9 figures, accepted for publication in Phys. Rev.
Self-Organized Criticality model for Brain Plasticity
Networks of living neurons exhibit an avalanche mode of activity,
experimentally found in organotypic cultures. Here we present a model based on
self-organized criticality and taking into account brain plasticity, which is
able to reproduce the spectrum of electroencephalograms (EEG). The model
consists in an electrical network with threshold firing and activity-dependent
synapse strenghts. The system exhibits an avalanche activity power law
distributed. The analysis of the power spectra of the electrical signal
reproduces very robustly the power law behaviour with the exponent 0.8,
experimentally measured in EEG spectra. The same value of the exponent is found
on small-world lattices and for leaky neurons, indicating that universality
holds for a wide class of brain models.Comment: 4 pages, 3 figure
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Genomic organization and single-nucleotide polymorphism map of desmuslin, a novel intermediate filament protein on chromosome 15q26.3
BACKGROUND: Desmuslin is an α-dystrobrevin-interacting protein expressed primarily in heart and skeletal muscle. The desmuslin protein interacts with and is closely related to desmin, a protein encoded by a locus mutated in some forms of hereditary distal myopathy. As a muscle-specific intermediate filament protein, desmuslin is also a candidate for myopathies of unknown etiology. RESULTS: The desmuslin gene was localized to chromosome 15q26.3 by electronic screening of the human DNA sequence database. Primer pairs were designed to amplify the 5 exons of the desmuslin gene in 11 overlapping DNA segments. The desmuslin gene was screened for mutations in 71 patients with various forms of myopathy for which there was no known cause. In this analysis, 10 common and 2 rare amino acid altering single-nucleotide polymorphisms were identified, all of which were seen in a control population of individuals thus making these unlikely causes of the phenotype. Interestingly, one of the single-nucleotide polymorphisms found in a patient resulted in a premature stop codon in the first exon. The nonsense mutation was also detected in the patient's unaffected father and one unaffected control; it was detected in 0.44% (2/454) of unrelated chromosomes and is therefore predicted to have a homozygous frequency of 0.002%. CONCLUSION: No causative mutations were found in the desmuslin gene. However, the single-nucleotide polymorphisms mapped in this study represent a well-mapped group that can be used for disequilibrium studies of this region of chromosome 15q26.3
TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres.
Shorter telomeres have been associated with increased risk of malignancy, including colorectal cancer (CRC). Telomere length is heritable and may be an intermediate phenotype linked to genetic susceptibility to CRC
Does the 1/f frequency-scaling of brain signals reflect self-organized critical states?
Many complex systems display self-organized critical states characterized by
1/f frequency scaling of power spectra. Global variables such as the
electroencephalogram, scale as 1/f, which could be the sign of self-organized
critical states in neuronal activity. By analyzing simultaneous recordings of
global and neuronal activities, we confirm the 1/f scaling of global variables
for selected frequency bands, but show that neuronal activity is not consistent
with critical states. We propose a model of 1/f scaling which does not rely on
critical states, and which is testable experimentally.Comment: 3 figures, 6 page
Aerial dissemination of Clostridium difficile spores
Background:
Clostridium difficile-associated diarrhoea (CDAD) is a frequently occurring healthcare-associated infection, which is responsible for significant morbidity and mortality amongst elderly patients in healthcare facilities. Environmental contamination is known to play an important contributory role in the spread of CDAD and it is suspected that contamination might be occurring as a result of aerial dissemination of C. difficile spores. However previous studies have failed to isolate C. difficile from air in hospitals. In an attempt to clarify this issue we undertook a short controlled pilot study in an elderly care ward with the aim of culturing C. difficile from the air.
Methods:
In a survey undertaken during February (two days) 2006 and March (two days) 2007, air samples were collected using a portable cyclone sampler and surface samples collected using contact plates in a UK hospital. Sampling took place in a six bedded elderly care bay (Study) during February 2006 and in March 2007 both the study bay and a four bedded orthopaedic bay (Control). Particulate material from the air was collected in Ringer's solution, alcohol shocked and plated out in triplicate onto Brazier's CCEY agar without egg yolk, but supplemented with 5 mg/L of lysozyme. After incubation, the identity of isolates was confirmed by standard techniques. Ribotyping and REP-PCR fingerprinting were used to further characterise isolates.
Results:
On both days in February 2006, C. difficile was cultured from the air with 23 samples yielding the bacterium (mean counts 53 – 426 cfu/m3 of air). One representative isolate from each of these was characterized further. Of the 23 isolates, 22 were ribotype 001 and were indistinguishable on REP-PCR typing. C. difficile was not cultured from the air or surfaces of either hospital bay during the two days in March 2007.
Conclusion:
This pilot study produced clear evidence of sporadic aerial dissemination of spores of a clone of C. difficile, a finding which may help to explain why CDAD is so persistent within hospitals and difficult to eradicate. Although preliminary, the findings reinforce concerns that current C. difficile control measures may be inadequate and suggest that improved ward ventilation may help to reduce the spread of CDAD in healthcare facilities
The Serre spectral sequence of a noncommutative fibration for de Rham cohomology
For differential calculi on noncommutative algebras, we construct a twisted
de Rham cohomology using flat connections on modules. This has properties
similar, in some respects, to sheaf cohomology on topological spaces. We also
discuss generalised mapping properties of these theories, and relations of
these properties to corings. Using this, we give conditions for the Serre
spectral sequence to hold for a noncommutative fibration. This might be better
read as giving the definition of a fibration in noncommutative differential
geometry. We also study the multiplicative structure of such spectral
sequences. Finally we show that some noncommutative homogeneous spaces satisfy
the conditions to be such a fibration, and in the process clarify the
differential structure on these homogeneous spaces. We also give two explicit
examples of differential fibrations: these are built on the quantum Hopf
fibration with two different differential structures.Comment: LaTeX, 33 page
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