506 research outputs found
The physical determinants of the thickness of lamellar polymer crystals
Based upon kinetic Monte Carlo simulations of crystallization in a simple
polymer model we present a new picture of the mechanism by which the thickness
of lamellar polymer crystals is constrained to a value close to the minimum
thermodynamically stable thickness. This description contrasts with those given
by the two dominant theoretical approaches.Comment: 4 pages, 4 figures, revte
Intraneural pseudocyst (so-called ganglion) in an unusual retroperitoneal periadnexal location?
A case of an unusual unilocular cystic lesion of diameter 7 cm located retroperitoneally in the pelvis in close
connection to the right adnexa of a 61 year-old woman is presented. Macroscopically, the lesion had a smooth
outer and inner surface and was filled with translucent fluid. Histological examination revealed a fibrous and
hyalinized wall which lacked a specific lining. Numerous nerve bundles in the cyst wall constituted the most
conspicuous element of its histology possibly with some contribution of perineurial and/or mesothelial components.
The morphology and immunohistochemistry speak for an intraneural pseudocyst sometimes called intraneural
ganglion cyst which is rare in this location
Intraneural pseudocyst (so-called ganglion) in an unusual retroperitoneal periadnexal location?
Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome
A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR). Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR) pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression
The next detectors for gravitational wave astronomy
This paper focuses on the next detectors for gravitational wave astronomy
which will be required after the current ground based detectors have completed
their initial observations, and probably achieved the first direct detection of
gravitational waves. The next detectors will need to have greater sensitivity,
while also enabling the world array of detectors to have improved angular
resolution to allow localisation of signal sources. Sect. 1 of this paper
begins by reviewing proposals for the next ground based detectors, and presents
an analysis of the sensitivity of an 8 km armlength detector, which is proposed
as a safe and cost-effective means to attain a 4-fold improvement in
sensitivity. The scientific benefits of creating a pair of such detectors in
China and Australia is emphasised. Sect. 2 of this paper discusses the high
performance suspension systems for test masses that will be an essential
component for future detectors, while sect. 3 discusses solutions to the
problem of Newtonian noise which arise from fluctuations in gravity gradient
forces acting on test masses. Such gravitational perturbations cannot be
shielded, and set limits to low frequency sensitivity unless measured and
suppressed. Sects. 4 and 5 address critical operational technologies that will
be ongoing issues in future detectors. Sect. 4 addresses the design of thermal
compensation systems needed in all high optical power interferometers operating
at room temperature. Parametric instability control is addressed in sect. 5.
Only recently proven to occur in Advanced LIGO, parametric instability
phenomenon brings both risks and opportunities for future detectors. The path
to future enhancements of detectors will come from quantum measurement
technologies. Sect. 6 focuses on the use of optomechanical devices for
obtaining enhanced sensitivity, while sect. 7 reviews a range of quantum
measurement options
Action spectroscopy of gas-phase carboxylate anions by multiple photon IR electron detachment/attachment
We report on a form of gas-phase anion action spectroscopy based on infrared
multiple photon electron detachment and subsequent capture of the free
electrons by a neutral electron scavenger in a Fourier Transform Ion Cyclotron
Resonance (FTICR) mass spectrometer. This method allows one to obtain
background-free spectra of strongly bound anions, for which no dissociation
channels are observed. The first gas-phase spectra of acetate and propionate
are presented using SF6 as electron scavenger and a free electron laser as
source of intense and tunable infrared radiation. To validate the method, we
compare infrared spectra obtained through multiple photon electron
detachment/attachment and multiple photon dissociation for the benzoate anion.
In addition, different electron acceptors are used, comparing both associative
and dissociative electron capture. The relative energies of dissociation (by
CO2 loss) and electron detachment are investigated for all three anions by DFT
and CCSD(T) methods. DFT calculations are also employed to predict vibrational
frequencies, which provide a good fit to the infrared spectra observed. The
frequencies of the symmetric and antisymmetric carboxylate stretching modes for
the aliphatic carboxylates are compared to those previously observed in
condensed-phase IR spectra and to those reported for gas-phase benzoate,
showing a strong influence of the solution environment and a slight substituent
effect on the antisymmetric stretch.Comment: Revised version, Submitted to J Phys Chem
Wilson Lines and a Canonical Basis of SU(4) Heterotic Standard Models
The spontaneous breaking of SU(4) heterotic standard models by Z_3 x Z_3
Wilson lines to the MSSM with three right-handed neutrino supermultiplets and
gauge group SU(3)_C x SU(2)_L x U(1) x U(1) is explored. The two-dimensional
subspace of the Spin(10) Lie algebra that commutes with su(3)_C + su(2)_L is
analyzed. It is shown that there is a unique basis for which the initial soft
supersymmetry breaking parameters are uncorrelated and for which the U(1) x
U(1) field strengths have no kinetic mixing at any scale. If the Wilson lines
"turn on" at different scales, there is an intermediate regime with either a
left-right or a Pati-Salam type model. We compute their spectra directly from
string theory, and adjust the associated mass parameter so that all gauge
parameters exactly unify. A detailed analysis of the running gauge couplings
and soft gaugino masses is presented.Comment: 59 pages, 9 figure
The Medium Is the Danger: Discourse about Television among Amish and Ultra-Orthodox (Haredi) Women
This study shows how Old Order Amish and ultra-Orthodox women’s discourse about television can help develop a better understanding of the creation, construction, and strengthening of limits and boundaries separating enclave cultures from the world. Based on questionnaires containing both closed- and open-ended questions completed by 82 participants, approximately half from each community, I argue that both communities can be understood as interpretive communities that negatively interpret not only television content, like other religious communities, but also the medium itself. Their various negative interpretive strategies is discussed and the article shows how they are part of an “us-versus-them” attitude created to mark the boundaries and walls that enclave cultures build around themselves. The comparison between the two communities found only a few small differences but one marked similarity: The communities perceive avoidance of a tool for communication, in this case television, as part of the communities’ sharing, participation, and common culture
No Remdesivir Resistance Observed in the Phase 3 Severe and Moderate COVID-19 SIMPLE Trials
Remdesivir (RDV) is a broad-spectrum nucleotide analog prodrug approved for the treatment of COVID-19 in hospitalized and non-hospitalized patients with clinical benefit demonstrated in multiple Phase 3 trials. Here we present SARS-CoV-2 resistance analyses from the Phase 3 SIMPLE clinical studies evaluating RDV in hospitalized participants with severe or moderate COVID-19 disease. The severe and moderate studies enrolled participants with radiologic evidence of pneumonia and a room-air oxygen saturation of ≤94% or >94%, respectively. Virology sample collection was optional in the study protocols. Sequencing and related viral load data were obtained retrospectively from participants at a subset of study sites with local sequencing capabilities (10 of 183 sites) at timepoints with detectable viral load. Among participants with both baseline and post-baseline sequencing data treated with RDV, emergent Nsp12 substitutions were observed in 4 of 19 (21%) participants in the severe study and none of the 2 participants in the moderate study. The following 5 substitutions emerged: T76I, A526V, A554V, E665K, and C697F. The substitutions T76I, A526V, A554V, and C697F had an EC50 fold change of ≤1.5 relative to the wildtype reference using a SARS-CoV-2 subgenomic replicon system, indicating no significant change in the susceptibility to RDV. The phenotyping of E665K could not be determined due to a lack of replication. These data reveal no evidence of relevant resistance emergence and further confirm the established efficacy profile of RDV with a high resistance barrier in COVID-19 patients
Notch Signaling Regulates Bile Duct Morphogenesis in Mice
BACKGROUND: Alagille syndrome is a developmental disorder caused predominantly by mutations in the Jagged1 (JAG1) gene, which encodes a ligand for Notch family receptors. A characteristic feature of Alagille syndrome is intrahepatic bile duct paucity. We described previously that mice doubly heterozygous for Jag1 and Notch2 mutations are an excellent model for Alagille syndrome. However, our previous study did not establish whether bile duct paucity in Jag1/Notch2 double heterozygous mice resulted from impaired differentiation of bile duct precursor cells, or from defects in bile duct morphogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Here we characterize embryonic biliary tract formation in our previously described Jag1/Notch2 double heterozygous Alagille syndrome model, and describe another mouse model of bile duct paucity resulting from liver-specific deletion of the Notch2 gene. CONCLUSIONS/SIGNIFICANCE: Our data support a model in which bile duct paucity in Notch pathway loss of function mutant mice results from defects in bile duct morphogenesis rather than cell fate specification
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