Lupin: a new hidden food allergen

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.William B Smith, David Gillis and Frank E Kett

Application of novel analytical ultracentrifuge analysis to solutions of fungal mannans

Polysaccharides, the most abundant biopolymers, are required for a host of activities in lower organisms, animals, and plants. Their solution characterization is challenging due to their complex shape, heterogeneity, and size. Here, recently developed data analysis approaches were applied for traditional sedimentation equilibrium and velocity methods in order to investigate the molar mass distribution(s) of a subtype of polysaccharide, namely, mannans from four Candida spp. The molecular weight distributions of these mannans were studied using two recently developed equilibrium approaches: SEDFIT-MSTAR and MULTISIG, resulting in corroboratory distribution profiles. Additionally, sedimentation velocity data for all four mannans, analyzed using ls-g*(s) and Extended Fujita approaches, suggest that two of the fungal mannans (FM-1 and FM-3) have a unimodal distribution of molecular species whereas two others (FM-2 and FM-4) displayed bi-modal and broad distributions, respectively: this demonstrates considerable molecular heterogeneity in these polysaccharides, consistent with previous observations of mannans and polysaccharides in general. These methods not only have applications for the characterization of mannans but for other biopolymers such as polysaccharides, DNA, and proteins (including intrinsically disordered proteins)

Astronaut Thermal Exposure: Re-Entry After Low Earth Orbit Rescue Mission

The STS-125 mission, launched May 11, 2009, is the final servicing mission to the Hubble Space Telescope. The repair mission's EVA tasks are described, including: installing a new wide field camera; installing the Cosmic Origins Spectrograph; repairing the Space Telescope Imaging Spectrograph; installing a new outer blanket layer; adding a Soft Capture and Rendezvous System for eventual controlled deorbit in about 2014; replacing the 'A' side Science Instrument Command and Data Handling module; repairing the Advanced Camera for surveys; and, replacing the rate sensor unit gyroscopes, fine guidance sensors and 3 batteries. Additionally, the Shuttle crew cabin thermal environment is described. A CFD model of per person CO2 demonstrates a discrepancy between crew breathing volume and general mid-deck levels of CO2. A follow-on CFD analysis of the mid-deck temperature distribution is provided. Procedural and engineering mitigation plans are presented to counteract thermal exposure upon reentry to the Earth atmosphere. Some of the procedures include: full cold soak the night prior to deorbit; modifying deck stowage to reduce interference with air flow; and early securing of avionics post-landing to reduce cabin thermal load prior to hatch opening. Engineering mitigation activities include modifying the location of the aft starboard ICUs, eliminating the X3 stack and eliminating ICU exhaust air directed onto astronauts; improved engineering data of ICU performance; and, verifying the adequacy of mid-deck temperature control using CFD models in addition to lumped parameter models. Post-mitigation CFD models of mid-deck temperature profiles and distribution are provided

The Apollo Medical Operations Project: Recommendations to Improve Crew Health and Performance for Future Exploration Missions and Lunar Surface Operations

Medical requirements for the future Crew Exploration Vehicle (CEV), Lunar Surface Access Module (LSAM), advanced Extravehicular Activity (EVA) suits and Lunar habitat are currently being developed. Crews returning to the lunar surface will construct the lunar habitat and conduct scientific research. Inherent in aggressive surface activities is the potential risk of injury to crewmembers. Physiological responses and the operational environment for short forays during the Apollo lunar missions were studied and documented. Little is known about the operational environment in which crews will live and work and the hardware will be used for long-duration lunar surface operations. Additional information is needed regarding productivity and the events that affect crew function such as a compressed timeline. The Space Medicine Division at the NASA Johnson Space Center (JSC) requested a study in December 2005 to identify Apollo mission issues relevant to medical operations that had impact to crew health and/or performance. The operationally oriented goals of this project were to develop or modify medical requirements for new exploration vehicles and habitats, create a centralized database for future access, and share relevant Apollo information with the multiple entities at NASA and abroad participating in the exploration effort

Characterisation of insulin analogues therapeutically available to patients

The structure and function of clinical dosage insulin and its analogues were assessed. This included ‘native insulins’ (human recombinant, bovine, porcine), ‘fast-acting analogues’ (aspart, glulisine, lispro) and ‘slow-acting analogues’ (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein

Empty spaces and the value of symbols: Estonia's 'war of monuments' from another angle

Taking as its point of departure the recent heightened discussion surrounding publicly sited monuments in Estonia, this article investigates the issue from the perspective of the country's eastern border city of Narva, focusing especially upon the restoration in 2000 of a 'Swedish Lion' monument to mark the 300th anniversary of Sweden's victory over Russia at the first Battle of Narva. This commemoration is characterised here as a successful local negotiation of a potentially divisive past, as are subsequent commemorations of the Russian conquest of Narva in 1704. A recent proposal to erect a statue of Peter the Great in the city, however, briefly threatened to open a new front in Estonia's ongoing 'war of monuments'. Through a discussion of these episodes, the article seeks to link the Narva case to broader conceptual issues of identity politics, nationalism and post-communist transition

Does knowledge of cancer diagnosis affect quality of life? A methodological challenge

BACKGROUND: As part of an assessment of quality of life in lung cancer patients an investigation was carried out to examine whether the knowledge of their diagnosis affected their quality of life. METHODS: Every patient in a defined geographical area with a potential diagnosis of lung cancer was interviewed at first consultation and after a definitive treatment has been given. Quality of life was assessed using three standard measures: the Nottingham Health Profile (NHP), the EORTC quality of life questionnaire (QLQ-C30) and its lung cancer supplementary questionnaire (QLQ-LC13). Comparison was made in quality of life scores between patients who knew their cancer diagnosis and those who did not. RESULTS: In all, 129 lung cancer patients were interviewed. Of these, 30 patients (23%) knew and 99 (78%) did not know their cancer diagnosis at the time of baseline assessment. The patient groups were similar in their characteristics except for age (P = 0.04) and cell type (P < 0.0001). Overall, there were no significant differences between these two groups with regard to their scores on the three instruments used. A major finding was that both group scored almost the same on emotional reactions (P = 0.8) and social isolation (P = 1.0) as measured by the NHP, and emotional (P = 0.7) and social functioning (P = 1.0) as measured by the EORTC QLQ-C30. In addition there were no significant differences in patients' symptom scores between those who knew their diagnosis and those who did not, nor did any consistent pattern emerge. The only significant difference was for sleep difficulties (P = 0.02). CONCLUSION: The findings suggest that the knowledge of cancer diagnosis does not affect the way in which patients respond to quality of life questionnaires

High resolution time-course mapping of early transcriptomic, molecular and cellular phenotypes in Huntington\u27s disease CAG knock-in mice across multiple genetic backgrounds.

Huntington\u27s disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in understanding the disease progression that leads from the HD mutation to massive cell death in the striatum is the ability to characterize the subtle and early functional consequences of the CAG expansion longitudinally. We used dense time course sampling between 4 and 20 postnatal weeks to characterize early transcriptomic, molecular and cellular phenotypes in the striatum of six distinct knock-in mouse models of the HD mutation. We studied the effects of the HttQ111 allele on the C57BL/6J, CD-1, FVB/NCr1, and 129S2/SvPasCrl genetic backgrounds, and of two additional alleles, HttQ92 and HttQ50, on the C57BL/6J background. We describe the emergence of a transcriptomic signature in HttQ111/+  mice involving hundreds of differentially expressed genes and changes in diverse molecular pathways. We also show that this time course spanned the onset of mutant huntingtin nuclear localization phenotypes and somatic CAG-length instability in the striatum. Genetic background strongly influenced the magnitude and age at onset of these effects. This work provides a foundation for understanding the earliest transcriptional and molecular changes contributing to HD pathogenesis

Predicting outcome in acute interstitial nephritis: a case series examining the importance of histological parameters

Background: The clinical significance of common histological parameters in acute interstitial nephritis (AIN) is uncertain. We aimed to evaluate the utility of histology in predicting clinical outcomes in patients with AIN. Methods and results: Adult renal biopsies yielding a diagnosis of AIN between 2000 and 2015 were re‐examined. Patients were divided into groups based on: 1) the percentage of non‐fibrotic cortex containing inflammation (NFI‐score), (NFI‐1=0‐24%, NFI‐2=25‐74%, NFI‐3=75‐100%), and 2) the percentage of cortex containing tubular atrophy (TA score), (TA1=0‐9%, TA2=10‐24%, TA3=25‐100%). The primary outcome was a composite of ≥50% reduction in serum creatinine (sCr) or an eGFR &gt;60 ml/min/1.73m2 1‐year post‐biopsy. From a total of 2817 native renal biopsies, there were 120 patients with AIN and adequate data for analysis. Of these, 66 (56%) achieved the primary outcome. On univariable logistic regression, NFI‐3 was associated with a 16 times increased likelihood of achieving the primary outcome compared to NFI‐1 (OR 16 (95% CI 5.2‐50)). In contrast, TA3 were associated with a 90% reduced likelihood of achieving the primary outcome compared to TA1 (OR=0.10 (95%CI 0.0‐0.3)). Maximal clinical utility was achieved by combining TA and NFI into a single prognostic ‘TANFI’ score, which had an independent predictive effect on the primary outcome in a multivariable regression model consisting of age, sex, baseline sCr and identified drug cause. Conclusions: In patients with biopsy‐proven AIN, a lower percentage of cortical tubular atrophy and, paradoxically, a higher percentage of inflammation in non‐fibrosed cortex were associated with an increased likelihood of a positive clinical outcome

Dissipative Chaos in Semiconductor Superlattices

We consider the motion of ballistic electrons in a miniband of a semiconductor superlattice (SSL) under the influence of an external, time-periodic electric field. We use the semi-classical balance-equation approach which incorporates elastic and inelastic scattering (as dissipation) and the self-consistent field generated by the electron motion. The coupling of electrons in the miniband to the self-consistent field produces a cooperative nonlinear oscillatory mode which, when interacting with the oscillatory external field and the intrinsic Bloch-type oscillatory mode, can lead to complicated dynamics, including dissipative chaos. For a range of values of the dissipation parameters we determine the regions in the amplitude-frequency plane of the external field in which chaos can occur. Our results suggest that for terahertz external fields of the amplitudes achieved by present-day free electron lasers, chaos may be observable in SSLs. We clarify the nature of this novel nonlinear dynamics in the superlattice-external field system by exploring analogies to the Dicke model of an ensemble of two-level atoms coupled with a resonant cavity field and to Josephson junctions.Comment: 33 pages, 8 figure