217 research outputs found
The Physics of the Colloidal Glass Transition
As one increases the concentration of a colloidal suspension, the system
exhibits a dramatic increase in viscosity. Structurally, the system resembles a
liquid, yet motions within the suspension are slow enough that it can be
considered essentially frozen. This kinetic arrest is the colloidal glass
transition. For several decades, colloids have served as a valuable model
system for understanding the glass transition in molecular systems. The spatial
and temporal scales involved allow these systems to be studied by a wide
variety of experimental techniques. The focus of this review is the current
state of understanding of the colloidal glass transition. A brief introduction
is given to important experimental techniques used to study the glass
transition in colloids. We describe features of colloidal systems near and in
glassy states, including tremendous increases in viscosity and relaxation
times, dynamical heterogeneity, and ageing, among others. We also compare and
contrast the glass transition in colloids to that in molecular liquids. Other
glassy systems are briefly discussed, as well as recently developed synthesis
techniques that will keep these systems rich with interesting physics for years
to come.Comment: 56 pages, 18 figures, Revie
Detailed spectral and morphological analysis of the shell type SNR RCW 86
Aims: We aim for an understanding of the morphological and spectral
properties of the supernova remnant RCW~86 and for insights into the production
mechanism leading to the RCW~86 very high-energy gamma-ray emission. Methods:
We analyzed High Energy Spectroscopic System data that had increased
sensitivity compared to the observations presented in the RCW~86 H.E.S.S.
discovery publication. Studies of the morphological correlation between the
0.5-1~keV X-ray band, the 2-5~keV X-ray band, radio, and gamma-ray emissions
have been performed as well as broadband modeling of the spectral energy
distribution with two different emission models. Results:We present the first
conclusive evidence that the TeV gamma-ray emission region is shell-like based
on our morphological studies. The comparison with 2-5~keV X-ray data reveals a
correlation with the 0.4-50~TeV gamma-ray emission.The spectrum of RCW~86 is
best described by a power law with an exponential cutoff at TeV and a spectral index of ~. A static
leptonic one-zone model adequately describes the measured spectral energy
distribution of RCW~86, with the resultant total kinetic energy of the
electrons above 1 GeV being equivalent to 0.1\% of the initial kinetic
energy of a Type I a supernova explosion. When using a hadronic model, a
magnetic field of ~100G is needed to represent the measured data.
Although this is comparable to formerly published estimates, a standard
E spectrum for the proton distribution cannot describe the gamma-ray
data. Instead, a spectral index of ~1.7 would be required, which
implies that ~erg has been transferred into
high-energy protons with the effective density cm^-3. This
is about 10\% of the kinetic energy of a typical Type Ia supernova under the
assumption of a density of 1~cm^-3.Comment: accepted for publication by A&
Detection of variable VHE gamma-ray emission from the extra-galactic gamma-ray binary LMC P3
Context. Recently, the high-energy (HE, 0.1-100 GeV) -ray emission
from the object LMC P3 in the Large Magellanic Cloud (LMC) has been discovered
to be modulated with a 10.3-day period, making it the first extra-galactic
-ray binary.
Aims. This work aims at the detection of very-high-energy (VHE, >100 GeV)
-ray emission and the search for modulation of the VHE signal with the
orbital period of the binary system.
Methods. LMC P3 has been observed with the High Energy Stereoscopic System
(H.E.S.S.); the acceptance-corrected exposure time is 100 h. The data set has
been folded with the known orbital period of the system in order to test for
variability of the emission. Energy spectra are obtained for the orbit-averaged
data set, and for the orbital phase bin around the VHE maximum.
Results. VHE -ray emission is detected with a statistical
significance of 6.4 . The data clearly show variability which is
phase-locked to the orbital period of the system. Periodicity cannot be deduced
from the H.E.S.S. data set alone. The orbit-averaged luminosity in the
TeV energy range is erg/s. A luminosity of erg/s is reached during 20% of the orbit. HE and VHE
-ray emissions are anti-correlated. LMC P3 is the most luminous
-ray binary known so far.Comment: 5 pages, 3 figures, 1 table, accepted for publication in A&
Characterizing the gamma-ray long-term variability of PKS 2155-304 with H.E.S.S. and Fermi-LAT
Studying the temporal variability of BL Lac objects at the highest energies
provides unique insights into the extreme physical processes occurring in
relativistic jets and in the vicinity of super-massive black holes. To this
end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in
the high (HE, 100 MeV 200 GeV)
gamma-ray domain. Over the course of ~9 yr of H.E.S.S observations the VHE
light curve in the quiescent state is consistent with a log-normal behavior.
The VHE variability in this state is well described by flicker noise
(power-spectral-density index {\ss}_VHE = 1.10 +0.10 -0.13) on time scales
larger than one day. An analysis of 5.5 yr of HE Fermi LAT data gives
consistent results ({\ss}_HE = 1.20 +0.21 -0.23, on time scales larger than 10
days) compatible with the VHE findings. The HE and VHE power spectral densities
show a scale invariance across the probed time ranges. A direct linear
correlation between the VHE and HE fluxes could neither be excluded nor firmly
established. These long-term-variability properties are discussed and compared
to the red noise behavior ({\ss} ~ 2) seen on shorter time scales during
VHE-flaring states. The difference in power spectral noise behavior at VHE
energies during quiescent and flaring states provides evidence that these
states are influenced by different physical processes, while the compatibility
of the HE and VHE long-term results is suggestive of a common physical link as
it might be introduced by an underlying jet-disk connection.Comment: 11 pages, 16 figure
The exceptionally powerful TeV gamma-ray emitters in the Large Magellanic Cloud
The Large Magellanic Cloud, a satellite galaxy of the Milky Way, has been
observed with the High Energy Stereoscopic System (H.E.S.S.) above an energy of
100 billion electron volts for a deep exposure of 210 hours. Three sources of
different types were detected: the pulsar wind nebula of the most energetic
pulsar known N 157B, the radio-loud supernova remnant N 132D and the largest
non-thermal X-ray shell - the superbubble 30 Dor C. The unique object SN 1987A
is, surprisingly, not detected, which constrains the theoretical framework of
particle acceleration in very young supernova remnants. These detections reveal
the most energetic tip of a gamma-ray source population in an external galaxy,
and provide via 30 Dor C the unambiguous detection of gamma-ray emission from a
superbubble.Comment: Published in Science Magazine (Jan. 23, 2015). This ArXiv version has
the supplementary online material incorporated as an appendix to the main
pape
Molecular and Antigenic Characterization of Reassortant H3N2 Viruses from Turkeys with a Unique Constellation of Pandemic H1N1 Internal Genes
Triple reassortant (TR) H3N2 influenza viruses cause varying degrees of loss in egg production in breeder turkeys. In this study we characterized TR H3N2 viruses isolated from three breeder turkey farms diagnosed with a drop in egg production. The eight gene segments of the virus isolated from the first case submission (FAV-003) were all of TR H3N2 lineage. However, viruses from the two subsequent case submissions (FAV-009 and FAV-010) were unique reassortants with PB2, PA, nucleoprotein (NP) and matrix (M) gene segments from 2009 pandemic H1N1 and the remaining gene segments from TR H3N2. Phylogenetic analysis of the HA and NA genes placed the 3 virus isolates in 2 separate clades within cluster IV of TR H3N2 viruses. Birds from the latter two affected farms had been vaccinated with a H3N4 oil emulsion vaccine prior to the outbreak. The HAl subunit of the H3N4 vaccine strain had only a predicted amino acid identity of 79% with the isolate from FAV-003 and 80% for the isolates from FAV-009 and FAV-0010. By comparison, the predicted amino acid sequence identity between a prototype TR H3N2 cluster IV virus A/Sw/ON/33853/2005 and the three turkey isolates from this study was 95% while the identity between FAV-003 and FAV-009/10 isolates was 91%. When the previously identified antigenic sites A, B, C, D and E of HA1 were examined, isolates from FAV-003 and FAV-009/10 had a total of 19 and 16 amino acid substitutions respectively when compared with the H3N4 vaccine strain. These changes corresponded with the failure of the sera collected from turkeys that received this vaccine to neutralize any of the above three isolates in vitro
Wild Type and Mutant 2009 Pandemic Influenza A (H1N1) Viruses Cause More Severe Disease and Higher Mortality in Pregnant BALB/c Mice
BACKGROUND: Pregnant women infected by the pandemic influenza A (H1N1) 2009 virus had more severe disease and higher mortality but its pathogenesis is still unclear. PRINCIPAL FINDINGS: We showed that higher mortality, more severe pneumonitis, higher pulmonary viral load, lower peripheral blood T lymphocytes and antibody responses, higher levels of proinflammatory cytokines and chemokines, and worse fetal development occurred in pregnant mice than non-pregnant controls infected by either wild type (clinical isolate) or mouse-adapted mutant virus with D222G substitution in hemagglutinin. These disease-associated changes and the lower respiratory tract involvement were worse in pregnant mice challenged by mutant virus. Though human placental origin JEG-3 cell line could be infected and proinflammatory cytokines or chemokines were elevated in amniotic fluid of some mice, no placental or fetal involvement by virus were detected by culture, real-time reverse transcription polymerase chain reaction or histopathological changes. Dual immunofluorescent staining of viral nucleoprotein and type II alveolar cell marker SP-C protein suggested that the majority of infected alveolar epithelial cells were type II pneumocytes. CONCLUSION: The adverse effect of this pandemic virus on maternal and fetal outcome is largely related to the severe pulmonary disease and the indirect effect of inflammatory cytokine spillover into the systemic circulation
Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis
Background
Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult.
Methods
Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays.
Results
The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells.
Conclusions
For the first time this data associates altered CDK5 substrate phosphorylation with oncogenesis in some but not all tumour types, implicating altered CDK5 activity in aspects of pathogenesis. These data identify a novel oncogenic mechanism where CDK5 activation induces CRMP2A phosphorylation in the nuclei of tumour cells
A Recombinant Vaccine of H5N1 HA1 Fused with Foldon and Human IgG Fc Induced Complete Cross-Clade Protection against Divergent H5N1 Viruses
Development of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus
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