Structural transitions of monoolein bicontinuous cubic phase induced by inclusion of protein lysozyme solutions

Inclusion of protein lysozyme molecules in lipidic monoolein cubic phase induces a transition from a $\rm Pn\bar{3}m$ structure to $\rm Im\bar{3}m$ one. Small-angle X-ray scattering (SAXS) method with high intensity synchrotron radiation enabled us to follow closely the transition depending on the conditions of lysozyme solutions. We showed that concentrated lysozyme solutions induced the appearance of the $\rm Im\bar{3}m$ structure coexisting with the $\rm Pn\bar{3}m$ structure. From the relation between the lattice parameters of these two structures it was shown that they were related by the Bonnet transformation of underlying triply periodic minimal surfaces. We found that the transition also occurred at lower lysozyme concentration when NaCl induced attraction between lysozyme molecules. The origin of the transition was considered as a frustration in the cubic phase where lysozyme molecules were highly confined. A simple estimation of the frustration was given, which took into account of the translational entropy of lysozyme molecules. At the highest concentration of lysozyme and NaCl the $\rm Im\bar{3}m$ structure was found to disappear and left only the $\rm Pn\bar{3}m$ structure. This was probably either due to the crystallization or phase separation of lysozyme solutions ongoing microscopically, which absorbed lysozyme molecules from channels of the cubic phase and thus removed the frustration.Comment: 8 pages, 5 figure

Moving Difference (MDIFF) Non-adiabatic Rapid Sweep (NARS) EPR of Copper(II)

Non-adiabatic rapid sweep (NARS) EPR spectroscopy has been introduced for application to nitroxide-labeled biological samples (Kittell et al., 2011). Displays are pure absorption, and are built up by acquiring data in spectral segments that are concatenated. In this paper we extend the method to frozen solutions of copper-imidazole, a square planar copper complex with four in-plane nitrogen ligands. Pure absorption spectra are created from concatenation of 170 5-gauss segments spanning 850 G at 1.9 GHz. These spectra, however, are not directly useful since nitrogen superhyperfine couplings are barely visible. Application of the moving difference (MDIFF) algorithm to the digitized NARS pure absorption spectrum is used to produce spectra that are analogous to the first harmonic EPR. The signal intensity is about four times higher than when using conventional 100 kHz field modulation, depending on line shape. MDIFF not only filters the spectrum, but also the noise, resulting in further improvement of the SNR for the same signal acquisition time. The MDIFF amplitude can be optimized retrospectively, different spectral regions can be examined at different amplitudes, and an amplitude can be used that is substantially greater than the upper limit of the field modulation amplitude of a conventional EPR spectrometer, which improves the signal-to-noise ratio of broad lines

Conformational transformations induced by the charge-curvature interaction at finite temperature

The role of thermal fluctuations on the conformational dynamics of a single closed filament is studied. It is shown that, due to the interaction between charges and bending degrees of freedom, initially circular aggregates may undergo transformation to polygonal shape. The transition occurs both in the case of hardening and softening charge-bending interaction. In the former case the charge and curvature are smoothly distributed along the chain while in the latter spontaneous kink formation is initiated. The transition to a non-circular conformation is analogous to the phase transition of the second kind.Comment: 23 pages (Latex), 10 figures (Postscript), 2 biblio file (bib-file and bbl-file

A telehealth approach to improving clinical trial access for infants with tuberous sclerosis complex.

BackgroundResearch in rare genetic syndromes associated with ASD is often hampered by the wide geographic distribution of families and the presence of medical comorbidities, such as epilepsy, that may preclude travel to clinical sites. These challenges can limit the sample size and generalizability of the cohorts included in both natural history studies and clinical trials. Tuberous sclerosis complex (TSC) is a rare genetic syndrome that confers an elevated risk for autism spectrum disorder (ASD), with social communication delays identified in this population as early as 12 months of age. Early identification of risk necessitates parallel testing of early intervention, prompting the first randomized controlled clinical trial of behavioral intervention for infants with TSC (NCT03422367). However, considerable early recruitment challenges have mandated the systematic identification of enrollment barriers followed by modification of the study design to address these barriers.MethodsCaregivers were interviewed regarding barriers to enrollment (phase 1). Adaptations to the intervention were made to address these barriers (phase 2). Outcomes based on this modification to the study design were defined by enrollment rate and participant demographics.ResultsQualitative reports from caregivers indicated that distance and time were the primary barriers to clinical trial enrollment. The intervention was then modified to a remote model, with at-home, parent-delivered intervention, and weekly video conferencing with interventionists at the study sites. Enrollment increased 10-fold (from 3 to 30 participants) within 1 year and included a more diverse and clinically representative cohort of infants.ConclusionThe design and implementation of more scalable methods to disseminate research remotely can substantially improve access to clinical trials in rare neurodevelopmental disorders. The lessons learned from this trial can serve as a model for future studies not only in rare conditions, but in other populations that lack adequate access, such as families with limited financial or clinical resources. Continued efforts will further refine delivery methods to enhance efficiency and ease of these delivery systems for families

Neutron spin structure with polarized deuterons and spectator proton tagging at EIC

The neutron's deep-inelastic structure functions provide essential information for the flavor separation of the nucleon parton densities, the nucleon spin decomposition, and precision studies of QCD phenomena in the flavor-singlet and nonsinglet sectors. Traditional inclusive measurements on nuclear targets are limited by dilution from scattering on protons, Fermi motion and binding effects, final-state interactions, and nuclear shadowing at x << 0.1. An Electron-Ion Collider (EIC) would enable next-generation measurements of neutron structure with polarized deuteron beams and detection of forward-moving spectator protons over a wide range of recoil momenta (0 < p_R < several 100 MeV in the nucleus rest frame). The free neutron structure functions could be obtained by extrapolating the measured recoil momentum distributions to the on-shell point. The method eliminates nuclear modifications and can be applied to polarized scattering, as well as to semi-inclusive and exclusive final states. We review the prospects for neutron structure measurements with spectator tagging at EIC, the status of R&D efforts, and the accelerator and detector requirements.Comment: 11 pages, 3 figures. To appear in proceedings of Tensor Polarized Solid Target Workshop, Jefferson Lab, March 10-12, 201

Re-evaluation of Cryptosporiopsis eucalypti and Cryptosporiopsis-like species occurring on Eucalyptus

Cryptosporiopsis eucalypti is a common follicolous pathogen of Eucalyptus species in tropical and temperate regions where these trees are grown in plantations. The taxonomy of C. eucalypti is confused by the fact that it is phylogenetically unrelated to the type species of Cryptosporiopsis (Cryptosporiopsis nigra = C. scutellata, Helotiales). The aim of this study was to resolve the taxonomic position of C. eucalypti based on morphology and phylogenetic inference. Thirty-two Eucalyptus leaf samples with symptoms typical of C. eucalypti infection were collected from 10 tropical and temperate countries across four continents. Cultures were established from single conidia, as well as from ascospores of a previously unreported teleomorph state. DNA sequences were obtained for the 28 S nrDNA, the internal transcribed spacers of the nrDNA operon, and beta-tubulin regions to determine generic and species-level relationships. DNA-sequence analysis showed that conidial and ascospore isolates of C. eucalypti have low intraspecific variation, although two collections from Australia and one from Uruguay represented two novel taxa. Based on the newly collected teleomorph stage, as well as the phylogenetic data, C. eucalypti is shown to represent a new genus closely related to Plagiostoma (Gnomoniaceae, Diaporthales) for which the names Pseudoplagiostoma gen. nov. and Pseudoplagiostomaceae fam. nov. (Diaporthales) are introduced. Two new species of Cryptosporiopsis (Dermateaceae, Helotiales) on Eucalyptus from Australia and California (USA) are also described

Attenuation of amiodarone induced lung fibrosis and phospholipidosis in hamsters, by treatment with the platelet activating factor receptor antagonist, WEB 2086

Therapeutic use of amiodarone (AMD), a Class III antiarrhythmic drug is complicated by the development of lung fibrosis (LF) and phospholipidosis (PL). In the present study, the effectiveness of a PAF antagonist, WEB 2086, against AMD induced LF and PL has been tested in hamsters. The animals were randomly divided into four groups: (1) saline + H2O; (2) WEB + H2O; (3) saline + AMD; and (4) WEB + AMD. Saline or WEB (10 mg/kg i.p.) was given 2 days prior to intratracheal instillation of water or AMD (1.5 μmol/0.25 ml/100 g BW) and thereafter daily throughout the study. Twenty-eight days after intratracheal instillation, the animals were killed and the lungs processed for various assays. The amount of lung hydroxyproline, an index of LF, in saline + H2O, WEB + H2O, saline + AMD, and WEB + AMD groups were 959 ± 46, 1035 ± 51, 1605 ± 85 and 1374 ± 69 μg/lung, respectively. Total lung PL, an index of phospholipidosis, in the corresponding groups were 8.4 ± 0.4, 8.3 ± 0.3, 11.7 ± 0.3 and 9.9 μg/lung. Lung malondialdehyde, an index of lipid peroxidation and superoxide dismutase activity in saline + H2O WEB + H2O, saline + AMD, and WEB + AMD were 93.0 ± 4.3, 93.0 ± 2.7, 138.9 ± 6.0 and 109.0 ± 3.8 nmol/lung and 359.7 ± 13.9, 394.0 ± 22.8, 497.5 ± 19.7 and 425.5 ± 4.9 units/lung, respectively. Administration of AMD alone caused significant increases in all the above indexes of lung toxicity, and treatment with WEB 2086 minimized the AMD induced toxicity as reflected by significant decreases in these indexes. Histopathological studies revealed a marked reduction in the extent and severity of lung lesions in the WEB + AMD group compared with the saline + AMD group. Treatment with WEB 2086 also reduced the acute mortality from 35% in saline + AMD group to 22% in WEB + AMD group. It was concluded that PAF is involved in the AMD induced lung fibrosis and phospholipidosis and that the PAF receptor antagonist may, therefore, be potentially useful in reducing AMD induced lung toxicity

Characteristics, accuracy and reverification of robotised articulated arm CMMs

VDI article 2617 specifies characteristics to describe the accuracy of articulated arm coordinate measuring machines (AACMMs) and outlines procedures for checking them. However the VDI prescription was written with a former generation of machines in mind: manual arms exploiting traditional touch probe technologies. Recent advances in metrology have given rise to noncontact laser scanning tools and robotic automation of articulated arms – technologies which are not adequately characterised using the VDI specification. In this paper we examine the “guidelines” presented in VDI 2617, finding many of them to be ambiguous and open to interpretation, with some tests appearing even to be optional. The engineer is left significant flexibility in the execution of the test procedures and the manufacturer is free to specify many of the test parameters. Such flexibility renders the VDI tests of limited value and the results can be misleading. We illustrate, with examples using the Nikon RCA, how a liberal interpretation of the VDI guidelines can significantly improve accuracy characterisation and suggest ways in which to mitigate this problem. We propose a series of stringent tests and revised definitions, in the same vein as VDI 2617 and similar US standards, to clarify the accuracy characterisation process. The revised methodology includes modified acceptance and reverification tests which aim to accommodate emerging technologies, laser scanning devices in particular, while maintaining the spirit of the existing and established standards. We seek to supply robust re-definitions for the accepted terms “zero point” and “useful arm length”, pre-supposing nothing about the geometry of the measuring device. We also identify a source of error unique to robotised AACMMs employing laser scanners – the forward-reverse pass error. We show how eliminating this error significantly improves the repeatability of a device and propose a novel approach to the testing of probing error based on statistical uncertainty