Coexistence of paraelectric/proton-glass and ferroelectric (antiferroelectric) orders in Rb₁₋x(NH₄)xH₂AsO₄ crystals

This paper reviews the results of dielectric studies of the proton glass state in a mixed crystal Rubidium Ammonium Dihydrogen Arsenate (RADA) The coexistence of paraelectric/proton glass and ferroelectric or antiferroelectric orders, confirmed by other studies, has been discussed in detail. The phase diagram of RADA is asymmetric. The proton glass state exists for ammonium concentration in the range of 0.1 < x < 0.5 . The phase diagram of deuterated DRADA is presented. The proton glass state region in DRADA, 0.2 < x < 0.35 is narrower than that for non-deuterated RADA. The effects of hydrostatic pressure on the dielectric properties in the proton glass state are presented. The glass temperature Tg decreases with pressure and is expected to vanish at 5 kbar. Low temperature behaviour is still an open question, since there is no experimental evidence of Tg(p) dependence below 4K for proton glass systems.Ця стаття є оглядом результатів діелектричного вивчення стану протонного скла у змішаних кристалах Rb₁₋x(NH₄)xH₂AsO₄ (RADA).Співіснування впорядкувань параелектричного/протонне скло та сегнетоелектричного чи антисегнетоелектричного, підтверджене іншими дослідженнями, детально обговорюється. Фазова діаграма RADA є асиметричною. Стан протонного скла існує для концентрації аміаку в межах 0, 1 < x < 0, 5 . Представлена фазова діаграма дейтерованого DRADA. Область стану протонного скла в DRADA (0, 2 < x < 0, 35) є вужчою, ніж у недейтерованому RADA. Представлені ефекти впливу гідростатичного тиску на діелектричні властивості кристалу в стані протонного скла. Температура склування Tg спадає з тиском і за оцінками прямує до нуля при 5 кбар. Низькотемпературна поведінка є все ще дискусійною, оскільки немає експериментально підтвердженої Tg(p) залежності нижче 4 К для систем протонного скла

Lipid dependence of peptide-membrane interactions Bilayer affinity and aggregation of the peptide alamethicin

AbstractMembrane incorporation and aggregation of the peptide alamethicin have been investigated as a function of lipid type. Head group and acyl chain regions both contribute to modulate alamethicin incorporation. Specifically, the peptide prefers thin membranes and saturated chains; incorporation is reduced by the presence of cholesterol. Aggregation of the peptide in the bilayer is virtually insensitive to changes in lipid composition. These findings show some analogies to results obtained with intrinsic membrane proteins and cast doubt on the use of global membrane parameters for interpreting lipid-peptide interactions

Design optimisation of separate-jet exhausts for the next generation of civil aero-engines

This paper presents the development and application of a computational framework for the aerodynamic design of separate-jet exhaust systems for Very-High-Bypass-Ratio (VHBR) gas-turbine aero-engines. An analytical approach is synthesised comprising a series of fundamental modelling methods. These address the aspects of engine performance simulation, parametric geometry definition, viscous/compressible flow solution, design space exploration, and genetic optimisation. Parametric design is carried out based on minimal user-input combined with the cycle data established using a zero-dimensional (0D) engine analysis method. A mathematical approach is developed based on Class-Shape Transformation (CST) functions for the parametric geometry definition of gas-turbine exhaust components such as annular ducts, nozzles, after-bodies, and plugs. This proposed geometry formulation is coupled with an automated mesh generation approach and a Reynolds Averaged Navier–Stokes (RANS) flow-field solution method, thus forming an integrated aerodynamic design tool. A cost-e ective Design Space Exploration (DSE) and optimisation strategy has been structured comprising methods for Design of Experiment (DOE), Response Surface Modelling (RSM), as well as genetic optimisation. The integrated framework has been deployed to optimise the aerodynamic performance of a separate-jet exhaust system for a large civil turbofan engine representative of future architectures. The optimisations carried out suggest the potential to increase the engine’s net propulsive force compared to a baseline architecture, through optimum re-design of the exhaust system. Furthermore, the developed approach is shown to be able to identify and alleviate adverse flow-features that may deteriorate the aerodynamic behaviour of the exhaust system

Geographical and seasonal barriers to mammography services and breast cancer stage at diagnosis

Introduction: Routine mammography screening and early detection are important prognostic indicators for breast cancer. Geographical and seasonal barriers to mammography services and relationship to breast cancer stage at diagnosis were examined. Methods: Travel time to mammography center, seasonal distribution of mammogram use, mammography frequency, and stage of cancer were retrospectively examined in 1428 female patients diagnosed with primary breast cancer at a tertiary care clinic system in Wisconsin, USA, from 2002 to 2008. Results: Women with no missed mammograms before diagnosis lived a median of 15 minutes from the nearest facility, while those who missed five of their past five annual mammograms lived nearly twice as far, with a median travel time of 27 minutes (p&#60;0.0001). There was a direct relationship between travel time to nearest mammogram facility and stage of breast cancer at diagnosis, with travel time increasing from 17 to 24 minutes for stage 0 and stage 4 breast cancers, respectively (p=0.0586). Women were less likely to undergo mammography screening during the winter months (p&#60;0.0001), especially women with greater than 30 mi (48.3 km) to travel to the nearest mammogram facility (p=0.0448). Conclusions: In the studied service area, travel time to nearest mammogram center appears inversely related to regular mammography screening and breast cancer stage at diagnosis. Mammograms are less common in the winter, especially in women with further to travel. This is the first study to demonstrate that inclement winter weather may impact on screening behaviors in rural areas and demonstrates the importance of considering climate as part of geographical access to preventative care

Thermodynamics and complex dielectric permittivity of mixed crystals of the Rb₁-x(NH₄)xH₂PO₄ type

We propose a pseudospin model for proton glasses of the Rb₁₋x(NH₄)xH₂PO₄(Rb₁₋x(ND₄)xD₂PO₄) type, which takes into account the energy levels of hydrogens (deuterons) around the PO₄ group, long-range interactions between the hydrogen bonds, and an internal random deformational field. Within the framework of a cluster approximation and a mean field approximation over the long-range interactions, we derive a system of equations for the state parameters for the regions which are in the ferroelectric and antiferroelectric states, as well as in the proton glass state. Within the Glauber dynamics approach, we obtain a system of equations for the frequency-dependent linear responses of polarization and the proton glass order parameter. We obtain a qualitative description of the temperature behavior of dielectric permittivities of the K₁₋x(ND₄)xD₂PO₄ and Rb₁₋x(NH₄)xH₂AsO₄ compounds at different frequencies. The origin of low-temperature peak in the imaginary part of dielectric permittivity in proton glasses is discussed.Запропонована псевдоспiнова модель протонних стекол типу Rb₁₋x(NH₄)xH₂PO₄(Rb₁₋x(ND₄)xD₂PO₄), яка враховує енергетичнi рiвнi протонiв (дейтронiв) бiля тетраедра PO₄, далекосяжну взаємодiю мiж водневими зв’язками i внутрiшнє хаотичне деформацiйне поле. В рамках кластерного наближення i наближення середнього поля по далекодiїї виведена система рiвнянь для параметрiв стану для областей, якi знаходяться в феро-, антифероелектричному станах, i в станi протонного скла. В рамках глауберiвської динамiки виведена система рiвнянь для частотнозалежних лiнiйних вiдгукiв полярiзацiї i параметра протонного скла. Отримано якiсний опис температурної поведiнки дiелектричних проникностей сполук K₁₋x(ND₄)xD₂PO₄ and Rb₁₋x(NH₄)xH₂AsO₄ при рiзних частотах. Обговорюються причини низькотемпературного пiку уявної частини дiелектричних проникностей в протонних стеклах

Installation aerodynamics of civil aero-engine exhaust systems

Without careful consideration of aerodynamic installation effects on exhaust system performance the projected benefits of high bypass ratio engines may not be achievable. This work presents a computational study of propulsion system integration in order to quantify the effect that aircraft installation has on the aerodynamic performance of separate-jet aero-engine exhaust systems. Within this study the sensitivity of exhaust nozzle performance metrics to aircraft incidence and under wing position were investigated for two engines of different specific thrust. Upon installation, thrust generation was found to be beneficial or detrimental relative to an isolated engine depending on the position of the engine relative to the wing leading edge. The dominant installation effect was observed on the exhaust afterbodies and, over the range of engine positions investigated at cruise conditions, the installed modified velocity coefficient was shown to vary up to 1 % relative to an isolated engine. Furthermore, due to variations in the core nozzle mass flow rate by up to 10% relative to an isolated engine, it is concluded that aerodynamic installation effects need to be taken into consideration when sizing the core nozzle in order to ensure engine operability

Chromosomal inversion polymorphisms are widespread across the species ranges of rough periwinkles (Littorina saxatilis and L. arcana)

Inversions are thought to play a key role in adaptation and speciation, suppressing recombination between diverging populations. Genes influencing adaptive traits cluster in inversions, and changes in inversion frequencies are associated with environmental differences. However, in many organisms, it is unclear if inversions are geographically and taxonomically widespread. The intertidal snail, Littorina saxatilis, is one such example. Strong associations between putative polymorphic inversions and phenotypic differences have been demonstrated between two ecotypes of L. saxatilis in Sweden and inferred elsewhere, but no direct evidence for inversion polymorphism currently exists across the species range. Using whole genome data from 107 snails, most inversion polymorphisms were found to be widespread across the species range. The frequencies of some inversion arrangements were significantly different among ecotypes, suggesting a parallel adaptive role. Many inversions were also polymorphic in the sister species, L. arcana, hinting at an ancient origin

A comparison of transgenic rodent mutation and in vivo comet assay responses for 91 chemicals.

A database of 91 chemicals with published data from both transgenic rodent mutation (TGR) and rodent comet assays has been compiled. The objective was to compare the sensitivity of the two assays for detecting genotoxicity. Critical aspects of study design and results were tabulated for each dataset. There were fewer datasets from rats than mice, particularly for the TGR assay, and therefore, results from both species were combined for further analysis. TGR and comet responses were compared in liver and bone marrow (the most commonly studied tissues), and in stomach and colon evaluated either separately or in combination with other GI tract segments. Overall positive, negative, or equivocal test results were assessed for each chemical across the tissues examined in the TGR and comet assays using two approaches: 1) overall calls based on weight of evidence (WoE) and expert judgement, and 2) curation of the data based on a priori acceptability criteria prior to deriving final tissue specific calls. Since the database contains a high prevalence of positive results, overall agreement between the assays was determined using statistics adjusted for prevalence (using AC1 and PABAK). These coefficients showed fair or moderate to good agreement for liver and the GI tract (predominantly stomach and colon data) using WoE, reduced agreement for stomach and colon evaluated separately using data curation, and poor or no agreement for bone marrow using both the WoE and data curation approaches. Confidence in these results is higher for liver than for the other tissues, for which there were less data. Our analysis finds that comet and TGR generally identify the same compounds (mainly potent mutagens) as genotoxic in liver, stomach and colon, but not in bone marrow. However, the current database content precluded drawing assay concordance conclusions for weak mutagens and non-DNA reactive chemicals

Overexpression of Parkinson's Disease-Associated Mutation LRRK2 G2019S in Mouse Forebrain Induces Behavioral Deficits and alpha-Synuclein Pathology

Citation: Xiong, Y. L., Neifert, S., Karuppagounder, S. S., Stankowski, J. N., Lee, B. D., Grima, J. C., . . . Dawson, V. L. (2017). Overexpression of Parkinson's Disease-Associated Mutation LRRK2 G2019S in Mouse Forebrain Induces Behavioral Deficits and alpha-Synuclein Pathology. Eneuro, 4(2), 10. https://doi.org/10.1523/eneuro.0004-17.2017Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified as an unambiguous cause of late-onset, autosomal-dominant familial Parkinson's disease (PD) and LRRK2 mutations are the strongest genetic risk factor for sporadic PD known to date. A number of transgenic mice expressing wild-type or mutant LRRK2 have been described with varying degrees of LRRK2-related abnormalities and modest pathologies. None of these studies directly addressed the role of the kinase domain in the changes observed and none of the mice present with robust features of the human disease. In an attempt to address these issues, we created a conditional LRRK2 G2019S (LRRK2 GS) mutant and a functionally negative control, LRRK2 G2019S/D1994A (LRRK2 GS/DA). Expression of LRRK2 GS or LRRK2 GS/DA was conditionally controlled using the tet-off system in which the presence of tetracycline-transactivator protein (tTA) with a CAMKII alpha promoter (CAMKII alpha-tTA) induced expression of TetP-LRRK2 GS or TetP-LRRK2 GS/DA in the mouse forebrain. Overexpression of LRRK2 GS in mouse forebrain induced behavioral deficits and alpha-synuclein pathology in a kinase-dependent manner. Similar to other genetically engineered LRRK2 GS mice, there was no significant loss of dopaminergic neurons. These mice provide an important new tool to study neurobiological changes associated with the increased kinase activity from the LRRK2 G2019S mutation, which may ultimately lead to a better understanding of not only the physiologic actions of LRRK2, but also potential pathologic actions that underlie LRRK2 GS-associated PD

Opportunities to integrate new approaches in genetic toxicology: An ILSI-HESI workshop report

Genetic toxicity tests currently used to identify and characterize potential human mutagens and carcinogens rely on measurements of primary DNA damage, gene mutation, and chromosome damage in vitro and in rodents. The International Life Sciences Institute Health and Environmental Sciences Institute (ILSI-HESI) Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity Testing held an April 2012 Workshop in Washington, DC, to consider the impact of new understanding of biology and new technologies on the identification and characterization of genotoxic substances, and to identify new approaches to inform more accurate human risk assessment for genetic and carcinogenic effects. Workshop organizers and speakers were from industry, academe, and government. The Workshop focused on biological effects and technologies that would potentially yield the most useful information for evaluating human risk of genetic damage. Also addressed was the impact that improved understanding of biology and availability of new techniques might have on genetic toxicology practices. Workshop topics included (1) alternative experimental models to improve genetic toxicity testing, (2) Biomarkers of epigenetic changes and their applicability to genetic toxicology, and (3) new technologies and approaches. The ability of these new tests and technologies to be developed into tests to identify and characterize genotoxic agents; to serve as a bridge between in vitro and in vivo rodent, or preferably human, data; or to be used to provide dose response information for quantitative risk assessment was also addressed. A summary of the workshop and links to the scientific presentations are provided.International Life Sciences Institute/Health and Environmental Sciences Institute Committe