bluuebunny/crossref_metadata_2025 huggingface dataset:
Was machst du denn da den ganzen Tag?
Authors: Deckelmann Beate , Kocks Andreas
Published: April 2018

Arbeitsalltag einer Schulkrankenschwester Das gebrochene Bein während des Sportunterrichts, der angeborene Herzfehler oder die Allergie bis hin zur Frage
der gesundheitsfördernden Mensa – die Erkenntnis, dass Themen der Gesundheit und Krankheit vor den Schultüren nicht Halt machen, setzt sich auch in Deutschland
zunehmend durch. International arbeiten in diesem Bereich an Schulen sogenannte School Nurses – Schulgesundheitspflegende. Die Chancen und Herausforderungen
sind groß, wie Beate Deckelmann, Schulgesundheitspflegerin an der BBIS, einer internationalen Schule in Brandenburg, aus ihrem Arbeitsalltag zu berichten
weiß.
Eine Reform, die es in sich hat
Authors: Franken Thomas
Published: April 2018

Was ist neu? Bei groß angekündigten Gesetzesreformen ist oftmals Skepsis angebracht. Nur allzu oft wird die Wirkung eines wohlgemeinten Vorhabens im
politischen Kompromisspoker so sehr aufgeweicht, dass nur noch bestenfalls ein Reförmchen übrig bleibt. Mit den sogenannten Pflegestärkungsgesetzen 2 und 3
verhält es sich hingegen grundlegend anders. Sie sind aus Sicht unseres Autors Thomas Franken der Einstieg in einen wirklichen Reformprozess und erschöpfen sich
eben nicht in lediglich partiellen Änderungen und den marginalen Drehungen an einzelnen Stellschrauben.
Boundary-induced pattern formation from uniform temporal oscillation
Authors: Kohsokabe Takahiro , Kaneko Kunihiko
Published: April 2018

Pattern dynamics triggered by fixing a boundary is investigated. By considering a reaction-diffusion equation that has a unique spatially uniform and limit cycle attractor under a periodic or Neumann boundary condition, and then by choosing a fixed boundary condition, we found three novel phases depending on the ratio of diffusion constants of activator to inhibitor: transformation of temporally periodic oscillation into a spatially periodic fixed pattern, travelling wave emitted from the boundary, and aperiodic spatiotemporal dynamics. The transformation into a fixed, periodic pattern is analyzed by crossing of local nullclines at each spatial point, shifted by diffusion terms, as is analyzed by using recursive equations, to obtain the spatial pattern as an attractor. The generality of the boundary-induced pattern formation as well as its relevance to biological morphogenesis is discussed.
Seismic isolation of small modular reactors using metamaterials
Authors: Witarto Witarto , Wang S. J. , Yang C. Y. , Nie Xin , Mo Y. L. , Chang K. C. , Tang Yu , Kassawara Robert
Published: April 2018

Adaptation of metamaterials at micro- to nanometer scales to metastructures at much larger scales offers a new alternative for seismic isolation systems. These new isolation systems, known as periodic foundations, function both as a structural foundation to support gravitational weight of the superstructure and also as a seismic isolator to isolate the superstructure from incoming seismic waves. Here we describe the application of periodic foundations for the seismic protection of nuclear power plants, in particular small modular reactors (SMR). For this purpose, a large-scale shake table test on a one-dimensional (1D) periodic foundation supporting an SMR building model was conducted. The 1D periodic foundation was designed and fabricated using reinforced concrete and synthetic rubber (polyurethane) materials. The 1D periodic foundation structural system was tested under various input waves, which include white noise, stepped sine and seismic waves in the horizontal and vertical directions as well as in the torsional mode. The shake table test results show that the 1D periodic foundation can reduce the acceleration response (transmissibility) of the SMR building up to 90%. In addition, the periodic foundation-isolated structure also exhibited smaller displacement than the non-isolated SMR building. This study indicates that the challenge faced in developing metastructures can be overcome and the periodic foundations can be applied to isolating vibration response of engineering structures.
Modulation period dependent mechanical properties of Cu/Fe metallic multilayered films
Authors: Gao Fengshan , Peng Xianghe , Huang Cheng , Yue Xing , Yang Bo , Sun Sha , Fu Tao
Published: April 2018

We performed molecular dynamics simulations for uniaxial tension of Cu/Fe nano-multilayered films with different modulation periods (λ) using Kurdjumov-Sachs (K-S) relationship to investigate their interfacial morphologies and the effects of λ on their mechanical properties. It shows that the mismatch dislocation lines at the interfaces are periodic. At the Cu side of the interface, triangles distribute with the smallest period; while at the Fe side, parallelograms distribute with the smallest period. There are two yield points, except the case of λ=2.10 nm where there is only one yield point, in the stress-strain curve of Cu/Fe multilayer film under tension, corresponding to the sequential nucleation of dislocations in the Cu and Fe layers from interface, respectively. We further found that there is a critical modulation period, λc, and the flow stress decreases with the increases of λ if λ > λc while increases with the increases of λ if λ < λc. The possible mechanisms are discussed.
Soft-mode driven polarity reversal in ferroelectrics mapped by ultrafast x-ray diffraction
Authors: Hauf Christoph , Hernandez Salvador Antonio-Andres , Holtz Marcel , Woerner Michael , Elsaesser Thomas
Published: April 2018

Quantum theory has linked microscopic currents and macroscopic polarizations of ferroelectrics, but the interplay of lattice excitations and charge dynamics on atomic length and time scales is an open problem. Upon phonon excitation in the prototypical ferroelectric ammonium sulfate [(NH4)2SO4], we determine transient charge density maps by femtosecond x-ray diffraction. A newly discovered low frequency-mode with a 3 ps period and sub-picometer amplitudes induces periodic charge relocations over some 100 pm, a hallmark of soft-mode behavior. The transient charge density allows for deriving the macroscopic polarization, showing a periodic reversal of polarity.
Measurement and analysis of time-domain characteristics of corona-generated radio interference from a single positive corona source
Authors: Li Xuebao , Li Dayong , Chen Bo , Cui Xiang , Lu Tiebing , Li Yinfei
Published: April 2018

The corona-generated electromagnetic interference commonly known as radio interference (RI) has become a limiting factor for the design of high voltage direct current transmission lines. In this paper, a time-domain measurement system is developed to measure the time-domain characteristics of corona-generated RI from a single corona source under a positive corona source. In the experiments, the corona current pulses are synchronously measured through coupling capacitors. The one-to-one relationship between the corona current pulse and measured RI voltage pulse is observed. The statistical characteristics of pulse parameters are analyzed, and the correlations between the corona current pulse and RI voltage pulse in the time-domain and frequency-domain are analyzed. Depending on the measured corona current pulses, the time-domain waveform of corona-generated RI is calculated on the basis of the propagation model of corona current on the conductor, the dipolar model for electric field calculation, and the antenna model for inducing voltage calculation. The well matched results between measured and simulated waveforms of RI voltage can show the validity of the measurement and calculation method presented in this paper, which also further show the close correlation between corona current and corona-generated RI.
Brown-midrib corn silage in finishing steer diet: effects on animal performance, in vivo digestibility and ruminal kinetics disappearance
Authors: Spetter M. J. , Ramiro F. A. , Della Rosa M. M. , Maglietti C. S. , Depetris J. G. , Santini F. J. , Raimondi J. P. , Roig J. M. , Pavan E.
Published: April 2018

Lower lignin content in brown-midrib corn silage (BMRCS) than in conventional corn silage results in greater digestibility and dry-matter intake. Despite this advantage, the use of BMRCS has not been widely evaluated in beef cattle. The aim of the present study was to determine the effects of BMRCS chopped at 22-mm as the main component (79% DM basis) for finishing steer diet on digestion, animal performance and ruminal kinetics disappearance. In a first trial, 56 Angus and crossbred steers (339 ± 18 kg initial bodyweight) were divided into 14 pens that were randomly assigned to one of the following two treatments: BMR total mixed ration (BMRT) or conventional total mixed ration. Data were analysed under a completely randomised design using pen as the experimental unit (n = 7). In a second trial, BMRCS and conventional corn silage were incubated (0, 3, 6, 12, 24, 36, 72 and 120 h) in the rumen of three ruminally cannulated cows. Data were analysed under a completely randomised block (cow) design. The inclusion of BMRCS in 79% corn silage diet for finishing steers improved total diet neutral detergent fibre and acid detergent fibre digestibility, but did not improve DM digestibility. While there was no significant improvement in animal performance, carcass yield was improved in BMRT. Future studies are needed to evaluate the improvement of carcass weight in steers fed BMRT.
Morphological and molecular systematics of the ‘Monanchora arbuscula complex’ (Poecilosclerida : Crambeidae), with the description of five new species and a biogeographic discussion of the genus in the Tropical Western Atlantic
Authors: Esteves Eduardo L. , de Paula Thiago S. , Lerner Clea , Lôbo-Hajdu Gisele , Hajdu Eduardo
Published: April 2018

Monanchora Carter, 1883 is a genus of shallow-water marine sponges comprising 16 species distributed worldwide, two of them in the Tropical Western Atlantic (TWA): M. arbuscula (Duchassaing & Michelotti, 1864) and M. brasiliensis Esteves, Lerner, Lôbo-Hajdu & Hajdu, 2012. The former species stands out as one of the most variable demosponges, and is very similar in spicule complement and in secondary metabolite chemistry to the Mediterranean/eastern Atlantic Crambe crambe (Schmidt, 1862), type species of Crambe Vosmaer, 1880. The aim of the present study was to revise the genus Monanchora in the TWA. In addition, we critically analyse the monophyly of Crambe and Monanchora. Maximum Likelihood and Bayesian Inference analyses of 28S and 16S rRNA sequences of the latter genera, and a redescription of the ‘M. arbuscula complex’, revealed three species: M. arbuscula s.s., M. coccinea, sp. nov. and a new species of Acarnidae – Iophon parvachela, sp. nov. Three other new species from the TWA previously assigned to Monanchora were revealed by morphological analyses, and are also described: M. bahamensis, sp. nov., M. megasigmifera, sp. nov. and a new species of Chondropsidae – Batzella catarinensis, sp. nov. A key for species identification is provided. Our results suggest that the Eastern Brazil and Southeastern Brazil Ecoregions may represent centres of diversity for Monanchora in the TWA.
Unexpected species diversity within Japanese Mundochthonius pseudoscorpions (Pseudoscorpiones : Chthoniidae) and the necessity for improved species diagnosis revealed by molecular and morphological examination
Authors: Ohira Hajime , Kaneko Shingo , Faulks Leanne , Tsutsumi Tadaaki
Published: April 2018

Using the complementary approaches of morphological and molecular taxonomy is essential to further our understanding of invertebrate diversity, including the identification of cryptic species. Although the species classification of a widespread group of arachnids, the pseudoscorpions, has been based on traditional diagnostic characters for a long time, recent taxonomic studies have suggested that some of these are unreliable for distinguishing species. Thus, the application of molecular taxonomy may be particularly useful in this group. Here, we performed molecular phylogenetic analyses and species delimitation analyses based on partial sequences of mitochondrial DNA cytochrome c oxidase I and nuclear DNA 18S rRNA genes to assess the taxonomy of species and the reliability of morphological characteristics for distinguishing species in the Japanese soil-dwelling genus Mundochthonius (Chthoniidae). Our results revealed the existence of seven major genetic clades, likely corresponding to three described species and four cryptic species. Although two described species, M. kiyoshii and M. itohi, were represented by single clades in the phylogenetic analysis, a third, M. japonicus, was composed of multiple clades, highlighting inconsistencies between phylogenetic relationships and current species classifications using traditional morphological diagnostics. This study exemplifies the need for further exploration of pseudoscorpion taxonomy and species diversity. In particular, detailed morphological examinations are expected to help determine differences among cryptic species.
Morphological phylogeny of the Australian genera of the bee fly subfamily Bombyliinae (Diptera : Bombyliidae) with description of four new genera
Authors: Li Xuankun , Yeates David K.
Published: April 2018

Bombyliinae, one of the largest subfamilies of Bombyliidae, including 78 genera assigned to four tribes, is distributed on all continents except Antarctica. Their larvae are parasitoids, and adults are important pollinators. The Australian Bombyliinae currently has 17 described genera and 87 described species. The purpose of this study is to establish the phylogeny of the Australian members of the subfamily Bombyliinae, including the boundaries and relationships of the genera, using morphological characters. One maximum parsimony tree was generated from 83 morphological characters scored for 50 species, representing all recognised genera and some unplaced species that we considered may represent new genera. Phylogenetic analysis recovered the relationships between the recognised Australian genera of Bombyliinae and clarified generic limits. The group comprises five main clades, with the genus Pilosia being sister to the remaining Bombyliinae. On the basis of this analysis, four new genera are described: Lambkinomyia Li & Yeates, gen. nov., Dissodesma Bowden & Li, gen. nov., Nigromyia Li & Yeates, gen. nov. and Robertsmyia Li & Yeates, gen. nov. Ten new species are described: Dissodesma immaculata Li & Yeates, sp. nov., Dissodesma flava Li & Yeates, sp. nov., Dissodesma smarti Li & Yeates, sp. nov., Nigromyia collessi Li & Yeates, sp. nov., Nigromyia crocea Li & Yeates, sp. nov., Nigromyia flavimana Li & Yeates, sp. nov., Nigromyia longistriata Li & Yeates, sp. nov., Nigromyia pantherina Li & Yeates, sp. nov., Nigromyia parva Li & Yeates, sp. nov. and Nigromyia tomentosa Li & Yeates, sp. nov. Two new junior synonyms are identified: Apiformyia is a junior synonym of Eristalopsis and Brychosoma is a junior synonym of Staurostichus. The following new combinations are proposed: from Apiformyia: Eristalopsis australis (Yeates), comb. nov.; from Bombylius: Dissodesma primogenita (Walker) comb. nov.; from Brychosoma: Staurostichus aureolatus (Walker), comb. nov., Staurostichus hilaris (Walker), comb. nov. and Staurostichus pictipennis (Macquart), comb. nov.; from Laurella: Robertsmyia pallidoventris (Roberts), comb. nov.; from Mandella: Lambkinomyia cinctiventris (Roberts), comb. nov., Lambkinomyia flavovillosa (Roberts), comb. nov., Lambkinomyia pallida (Roberts), comb. nov. and Lambkinomyia rubida (Roberts), comb. nov.; and from Meomyia: Mandella australis (Guérin-Méneville), comb. nov. http://zoobank.org/urn:lsid:zoobank.org:pub:E4A86A19-4AC3-498C-8BDF-B8B501E5A248
Supporting primary care nurses to work at an advanced level through changing practices’ organisational governance
Authors: Forsdike Kirsty , Murphy Tracy Ann , Hegarty Kelsey
Published: April 2018

General practice nurses wishing to develop their careers in general practice are often unsupported, relying on the culture of individual practices. Given the structural diversity of Australian general practice, we qualitatively explored staff experiences of organisational governance, what supports are in place and can be used to assist nurses to advance. Semi-structured interviews with 28 staff (including nurses, GPs, receptions and practice managers) were undertaken across three practices, as part of a case-study approach. It was found that general practice staff know little of organisational governance and how it may be harnessed. Practical and flexible organisational governance were the most important factors in supporting general practice nurses to develop and utilise nursing skills, but advocacy from medical colleagues was necessary to support advancement. Barriers include funding structures, non-supportive cultures and inflexible organisational governance structures. Organisation governance has the potential to assist nurses to work at an advanced level, but significant financial, structural and cultural barriers may be too difficult for organisational governance resources alone to overcome. In addition to utilising resources, it may be useful for general practices to undertake a review of how they function as a team and reflect upon their practice culture.
Partners in Recovery: paving the way for the National Disability Insurance Scheme
Authors: Stewart Victoria , Slattery Maddy , Roennfeldt Helena , Wheeler Amanda J.
Published: April 2018

Australians experiencing severe and persistent mental illness and who require services from multiple agencies, experience a fragmented service delivery system. In 2014, the Commonwealth Government introduced the Partners in Recovery (PIR) service, which provides service coordination and flexible funding to improve outcomes for this group of people. This study presents qualitative findings from a research project that aimed to understand the experiences of PIR participants, including aspects of the planning process and the effectiveness of the PIR program in meeting their needs from the perspective of the participant, their carer or family member and other support people within their lives. Semi-structured interviews were conducted with 31 stakeholders involved in the PIR program, of which 14 were participants, 17 were members of the participant’s support network and three were members of a consumer and carer advisory group. Overall participation in the PIR program had a positive effect on the participant’s lives. Relationships with the support facilitators were seen as an important element of the process, along with a focus on recovery-oriented goals and advocacy and linking to other agencies. These findings are important for informing the roll-out of the National Disability Insurance Scheme in Australia, which will replace PIR.
Pervasive contingency and entrenchment in a billion years of Hsp90 evolution
Authors: Starr Tyler N. , Flynn Julia M. , Mishra Parul , Bolon Daniel N. A. , Thornton Joseph W.
Published: April 2018

Significance

When mutations within a protein change each other’s functional effects—a phenomenon called epistasis—the paths available to evolution at any moment in time depend on the specific set of changes that previously occurred in the protein. The extent to which epistasis has shaped historical evolutionary trajectories is unknown. Using a high-precision bulk fitness assay and ancestral protein reconstruction, we measured the fitness effects in ancestral and extant sequences of all historical substitutions that occurred during the billion-year trajectory of an essential protein. We found that most historical substitutions were contingent on prior epistatic substitutions and/or entrenched by subsequent changes. These results establish that epistasis caused widespread, consequential shifts in the site-specific fitness constraints that shaped the protein’s historical trajectory.
Identification of EGFR in pearl oyster (Pinctada fucata martensii) and correlation analysis of its expression and growth traits
Authors: Wang Qingheng , Hao Ruijuan , Zhao Xiaoxia , Huang Ronglian , Zheng Zhe , Deng Yuewen , Chen Weiyao , Du Xiaodong
Published: April 2018

Marine pearl production is directly influenced by the growth speed of Pinctada fucata martensii. However, the slow growth rate of this organism remains the main challenge in aquaculture production. Epidermal growth factor receptor (EGFR), an important receptor of tyrosine kinases in animals, plays versatile functions in development, growth and tissue regeneration. In this study, we described the characteristic and function of an EGFR gene identified from P. f. martensii (PmEGFR). PmEGFR possesses a typical EGFR structure and is expressed in all studied tissues, with the highest expression level in adductor muscle. PmEGFR expression level is significantly higher in the fast-growing group than that in the slow-growing one. Correlation analysis represents that shell height and shell weight show positive correlation with PmEGFR expression (p < 0.05), and total weight and tissue weight exhibit positive correlation with it (p < 0.01). This study indicates that PmEGFR is a valuable functional gene associated with growth traits.
Unique GH18 chitinase fromEuglena gracilis: full-length cDNA cloning and characterization of its catalytic domain
Authors: Taira Toki , Gushiken Chika , Sugata Kobeni , Ohnuma Takayuki , Fukamizo Tamo
Published: April 2018

A cDNA of putative chitinase from Euglena gracilis, designated EgChiA, encoded 960 amino acid residues, which is arranged from N-terminus in the order of signal peptide, glycoside hydrolase family 18 (GH18) domain, carbohydrate binding module family 18 (CBM18) domain, GH18 domain, CBM18 domain, and transmembrane helix. It is likely that EgChiA is anchored on the cell surface. The recombinant second GH18 domain of EgChiA, designated as CatD2, displayed optimal catalytic activity at pH 3.0 and 50 °C. The lower the polymerization degree of the chitin oligosaccharides [(GlcNAc)4–6] used as the substrates, the higher was the rate of degradation by CatD2. CatD2 degraded chitin nanofibers as an insoluble substrate, and it produced only (GlcNAc)2 and GlcNAc. Therefore, we speculated that EgChiA localizes to the cell surface of E. gracilis and is involved in degradation of chitin polymers into (GlcNAc)2 or GlcNAc, which are easily taken up by the cells.
How autocracy impedes de-securitization, or why democracy matters: the case of Nagorno-Karabagh in the eyes of Azerbaijanis
Authors: Alieva Leila , Aslanov Bakhtiyar
Published: April 2018

This article analyses the democracy/security nexus by looking at how autocratic rule guides popular opinion in what have come to be known as “frozen conflicts”. In tackling the role of democracy in security, we draw on the concepts of “securitization” and “desecuritization”. Based on the studies of Buzan, Waever and Aradau, we extend current approaches to desecuritization by indicating how democratic systems can unleash emancipatory social processes. This helps us understand not only the limited nature of de-securitization by autocrats, but also the impediments that autocratic rule presents to de-securitization from below. Besides direct limits placed on political freedoms, autocratic governments can prevent the liberalization and modernization of views in society through economic control and reproduction of the dominant socio-economic structures. Based on an uncommonly wide range of interviews, this article shows how a broader set of views affects the views on conflict and its resolution.
Centromere transcription allows CENP-A to transit from chromatin association to stable incorporation
Authors: Bobkov Georg O.M. , Gilbert Nick , Heun Patrick
Published: April 2018

Centromeres are essential for chromosome segregation and are specified epigenetically by the presence of the histone H3 variant CENP-A. In flies and humans, replenishment of the centromeric mark is uncoupled from DNA replication and requires the removal of H3 “placeholder” nucleosomes. Although transcription at centromeres has been previously linked to the loading of new CENP-A, the underlying molecular mechanism remains poorly understood. Here, we used Drosophila melanogaster tissue culture cells to show that centromeric presence of actively transcribing RNA polymerase II temporally coincides with de novo deposition of dCENP-A. Using a newly developed dCENP-A loading system that is independent of acute transcription, we found that short inhibition of transcription impaired dCENP-A incorporation into chromatin. Interestingly, initial targeting of dCENP-A to centromeres was unaffected, revealing two stability states of newly loaded dCENP-A: a salt-sensitive association with the centromere and a salt-resistant chromatin-incorporated form. This suggests that transcription-mediated chromatin remodeling is required for the transition of dCENP-A to fully incorporated nucleosomes at the centromere.
Macrophage/microglial Ezh2 facilitates autoimmune inflammation through inhibition of Socs3
Authors: Zhang Xingli , Wang Yan , Yuan Jia , Li Ni , Pei Siyu , Xu Jing , Luo Xuan , Mao Chaoming , Liu Junli , Yu Tao , Gan Shucheng , Zheng Qianqian , Liang Yinming , Guo Weixiang , Qiu Ju , Constantin Gabriela , Jin Jin , Qin Jun , Xiao Yichuan
Published: April 2018

Histone 3 Lys27 (H3K27) trimethyltransferase Ezh2 is implicated in the pathogenesis of autoimmune inflammation. Nevertheless, the role of Ezh2 in macrophage/microglial activation remains to be defined. In this study, we identified that macrophage/microglial H3K27me3 or Ezh2, rather than functioning as a repressor, mediates toll-like receptor (TLR)-induced proinflammatory gene expression, and therefore Ezh2 depletion diminishes macrophage/microglial activation and attenuates the autoimmune inflammation in dextran sulfate sodium–induced colitis and experimental autoimmune encephalomyelitis. Mechanistic characterizations indicated that Ezh2 deficiency directly stimulates suppressor of cytokine signaling 3 (Socs3) expression and therefore enhances the Lys48-linked ubiquitination and degradation of tumor necrosis factor receptor–associated factor 6. As a consequence, TLR-induced MyD88-dependent nuclear factor κB activation and the expression of proinflammatory genes in macrophages/microglia are compromised in the absence of Ezh2. The functional dependence of Ezh2 for Socs3 is further illustrated by the rescue experiments in which silencing of Socs3 restores macrophage activation and rescues autoimmune inflammation in macrophage/microglial Ezh2-deficient mice. Together, these findings establish Ezh2 as a macrophage lineage-specific mediator of autoimmune inflammation and highlight a previously unknown mechanism of Ezh2 function.
Combination anti-Aβ treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice
Authors: Chiang Angie C.A. , Fowler Stephanie W. , Savjani Ricky R. , Hilsenbeck Susan G. , Wallace Clare E. , Cirrito John R. , Das Pritam , Jankowsky Joanna L.
Published: April 2018

Drug development for Alzheimer’s disease has endeavored to lower amyloid β (Aβ) by either blocking production or promoting clearance. The benefit of combining these approaches has been examined in mouse models and shown to improve pathological measures of disease over single treatment; however, the impact on cellular and cognitive functions affected by Aβ has not been tested. We used a controllable APP transgenic mouse model to test whether combining genetic suppression of Aβ production with passive anti-Aβ immunization improved functional outcomes over either treatment alone. Compared with behavior before treatment, arresting further Aβ production (but not passive immunization) was sufficient to stop further decline in spatial learning, working memory, and associative memory, whereas combination treatment reversed each of these impairments. Cognitive improvement coincided with resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of hyperactive mammalian target of rapamycin signaling. Computational modeling corroborated by in vivo microdialysis pointed to the reduction of soluble/exchangeable Aβ as the primary driver of cognitive recovery.
Atom-by-atom tuning of the electrostatic potassium-channel modulator dehydroabietic acid
Authors: Silverå Ejneby Malin , Wu Xiongyu , Ottosson Nina E. , Münger E. Peter , Lundström Ingemar , Konradsson Peter , Elinder Fredrik
Published: April 2018

Dehydroabietic acid (DHAA) is a naturally occurring component of pine resin that was recently shown to open voltage-gated potassium (KV) channels. The hydrophobic part of DHAA anchors the compound near the channel’s positively charged voltage sensor in a pocket between the channel and the lipid membrane. The negatively charged carboxyl group exerts an electrostatic effect on the channel’s voltage sensor, leading to the channel opening. In this study, we show that the channel-opening effect increases as the length of the carboxyl-group stalk is extended until a critical length of three atoms is reached. Longer stalks render the compounds noneffective. This critical distance is consistent with a simple electrostatic model in which the charge location depends on the stalk length. By combining an effective anchor with the optimal stalk length, we create a compound that opens the human KV7.2/7.3 (M type) potassium channel at a concentration of 1 µM. These results suggest that a stalk between the anchor and the effector group is a powerful way of increasing the potency of a channel-opening drug.
Filament winding technique, experiment and simulation analysis on tubular structure
Authors: Quanjin Ma , Rejab M R M , Kaige Jiang , Idris M S , Harith M N
Published: April 2018

Filament winding process has emerged as one of the potential composite fabrication processes with lower costs. Filament wound products involve classic axisymmetric parts (pipes, rings, driveshafts, high-pressure vessels and storage tanks), non-axisymmetric parts (prismatic nonround sections and pipe fittings). Based on the 3-axis filament winding machine has been designed with the inexpensive control system, it is completely necessary to make a relative comparison between experiment and simulation on tubular structure. In this technical paper, the aim of this paper is to perform a dry winding experiment using the 3-axis filament winding machine and simulate winding process on the tubular structure using CADWIND software with 30°, 45°, 60° winding angle. The main result indicates that the 3-axis filament winding machine can produce tubular structure with high winding pattern performance with different winding angle. This developed 3-axis winding machine still has weakness compared to CAWIND software simulation results with high axes winding machine about winding pattern, turnaround impact, process error, thickness, friction impact etc. In conclusion, the 3-axis filament winding machine improvements and recommendations come up with its comparison results, which can intuitively understand its limitations and characteristics.
Charity and the End of Empire: British Non-Governmental Organizations, Africa, and International Development in the 1960s
Authors: Hilton Matthew
Published: April 2018

British non-governmental organizations (NGOs) became a part of the modern aid industry in the 1960s, particularly across Africa. At the moment of decolonization, humanitarian charities were recast into modern NGOs focused on small-scale grassroots initiatives nevertheless tied to long-term official development planning. NGOs and charities were popular because they represented many things for many people. For the late colonial state, they were the agents that would step in where government retreated, providing vital lessons in self-help for the future leaders of the country. For newly independent governments, they were both suppliers of Western funds and props to impoverished social service departments. For donors and international aid agencies, they were a route through which liberal internationalist sympathies could be directed. That no one in these early decades of development was certain which aid initiatives actually worked on the ground was therefore of less importance than the optimistic hopes placed upon charity to tackle global poverty. Indeed, it was the ad hoc, confusing, and complex landscape of charitable aid that lay behind the rise of the modern NGO. For a variety of reasons, all had a stake in their continued presence and expansion across the developing world.
Circulating non-coding RNAs in biomarker-guided cardiovascular therapy: a novel tool for personalized medicine?
Authors: de Gonzalo-Calvo David , Vea Angela , Bär Christian , Fiedler Jan , Couch Liam S , Brotons Carlos , Llorente-Cortes Vicenta , Thum Thomas
Published: April 2018

Current clinical guidelines emphasize the unmet need for technological innovations to guide physician decision-making and to transit from conventional care to personalized cardiovascular medicine. Biomarker-guided cardiovascular therapy represents an interesting approach to inform tailored treatment selection and monitor ongoing efficacy. However, results from previous publications cast some doubts about the clinical applicability of biomarkers to direct individualized treatment. In recent years, the non-coding human transcriptome has emerged as a new opportunity for the development of novel therapeutic strategies and biomarker discovery. Non-coding RNA (ncRNA) signatures may provide an accurate molecular fingerprint of patient phenotypes and capture levels of information that could complement traditional markers and established clinical variables. Importantly, ncRNAs have been identified in body fluids and their concentrations change with physiology and pathology, thus representing promising non-invasive biomarkers. Previous publications highlight the translational applicability of circulating ncRNAs for diagnosis and prognostic stratification within cardiology. Numerous independent studies have also evaluated the potential of the circulating non-coding transcriptome to predict and monitor response to cardiovascular treatment. However, this field has not been reviewed in detail. Here, we discuss the state-of-the-art research into circulating ncRNAs, specifically microRNAs and long non-coding RNAs, to support clinical decision-making in cardiovascular therapy. Furthermore, we summarize current methodological and conceptual limitations and propose future steps for their incorporation into personalized cardiology. Despite the lack of robust population-based studies and technical barriers, circulating ncRNAs emerge as a promising tool for biomarker-guided therapy.
EMC10 governs male fertility via maintaining sperm ion balance
Authors: Zhou Yuchuan , Wu Fei , Zhang Man , Xiong Zuquan , Yin Qianqian , Ru Yanfei , Shi Huijuan , Li Jinsong , Mao Shanhua , Li Yanliang , Cao Xinyi , Hu Renming , Liew Chong Wee , Ding Qiang , Wang Xuanchun , Zhang Yonglian
Published: April 2018

Infertility is a severe public health problem worldwide that prevails up to 15% in reproductive-age couples, and male infertility accounts for half of total infertility. Studies on genetically modified animal models have identified lots of genes involved in the pathogenesis of male infertility. The underlying causes, however, remain largely unclear. In this study, we provide evidence that EMC10, one subunit of endoplasmic reticulum (ER) membrane protein complex (EMC), is required for male fertility. EMC10 is significantly decreased in spermatozoa from patients with asthenozoospermia and positively associated with human sperm motility. Male mice lacking Emc10 gene are completely sterile. Emc10-null spermatozoa exhibit multiple defects including abnormal morphology, decreased motility, impaired capacitation, and impotency of acrosome reaction, thereby which are incapable of fertilizing intact or ZP-free oocytes. However, intracytoplasmic sperm injection could rescue this defect caused by EMC10 deletion. Mechanistically, EMC10 deficiency leads to inactivation of Na/K-ATPase, in turn giving rise to an increased level of intracellular Na+ in spermatozoa, which contributes to decreased sperm motility and abnormal morphology. Other mechanistic investigations demonstrate that the absence of EMC10 results in a reduction of HCO3− entry and subsequent decreases of both cAMP-dependent protein kinase A substrate phosphorylation and protein tyrosine phosphorylation. These data demonstrate that EMC10 is indispensable to male fertility via maintaining sperm ion balance of Na+ and HCO3−, and also suggest that EMC10 is a promising biomarker for male fertility and a potential pharmaceutical target to treat male infertility.
Case Report of an Extensively Drug-Resistant Klebsiella pneumoniae Infection With Genomic Characterization of the Strain and Review of Similar Cases in the United States
Authors: Krapp Fiorella , Ozer Egon A , Qi Chao , Hauser Alan R
Published: April 2018

Reports of extensively drug-resistant and pan-drug-resistant Klebsiella pneumoniae (XDR-KP and PDR-KP) cases are increasing worldwide. Here, we report a case of XDR-KP with an in-depth molecular characterization of resistance genes using whole-genome sequencing, and we review all cases of XDR-KP and PDR-KP reported in the United States to date.
Neurocognitive Function after Cardiac Surgery
Authors: Berger Miles , Terrando Niccolò , Smith S. Kendall , Browndyke Jeffrey N. , Newman Mark F. , Mathew Joseph P.
Published: April 2018

For half a century, it has been known that some patients experience neurocognitive dysfunction after cardiac surgery; however, defining its incidence, course, and causes remains challenging and controversial. Various terms have been used to describe neurocognitive dysfunction at different times after cardiac surgery, ranging from “postoperative delirium” to “postoperative cognitive dysfunction or decline.” Delirium is a clinical diagnosis included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Postoperative cognitive dysfunction is not included in the DSM-5 and has been heterogeneously defined, though a recent international nomenclature effort has proposed standardized definitions for it. Here, the authors discuss pathophysiologic mechanisms that may underlie these complications, review the literature on methods to prevent them, and discuss novel approaches to understand their etiology that may lead to novel treatment strategies. Future studies should measure both delirium and postoperative cognitive dysfunction to help clarify the relationship between these important postoperative complications.
Working Memory Training Following Neonatal Critical Illness: A Randomized Controlled Trial*
Authors: Schiller Raisa M. , Madderom Marlous J. , van Rosmalen Joost , van Heijst Arno F. J. , de Blaauw Ivo , Utens Elisabeth , Rietman André B. , Verhulst Frank , Tibboel Dick , White Tonya , IJsselstijn Hanneke
Published: April 2018

Objectives:

To test the immediate and long-term effectiveness of Cogmed Working Memory Training following extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia.

Design:

A nationwide randomized controlled trial assessing neuropsychologic outcome immediately and 1 year post Cogmed Working Memory Training, conducted between October 2014 and June 2017. Researchers involved in the follow-up assessments were blinded to group allocation.

Setting:

Erasmus MC-Sophia Children’s Hospital, Rotterdam, and Radboud University Medical Center, Nijmegen, the Netherlands.

Patients:

Eligible participants were neonatal extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia survivors (8–12 yr) with an intelligence quotient greater than or equal to 80 and azscore less than or equal to –1.5 on at least one (working) memory test at first assessment.

Interventions:

Cogmed Working Memory Training, comprising 25 45-minute training sessions for 5 consecutive weeks at home.

Measurements and Main Results:

Participants were randomized to Cogmed Working Memory Training (n= 19) or no intervention (n= 24) (two dropped out after T0). Verbal working memory (estimated coefficient = 0.87;p= 0.002) and visuospatial working memory (estimated coefficient=0.96,p= 0.003) significantly improved at T1 post Cogmed Working Memory Training but was similar between groups at T2 (verbal,p= 0.902; visuospatial,p= 0.416). Improvements were found at T2 on long-term visuospatial memory following Cogmed Working Memory Training (estimated coefficient = 0.95;p= 0.003). Greater improvements in this domain at T2 following Cogmed Working Memory Training were associated with better self-rated school functioning (r= 0.541;p= 0.031) and parent-rated attention (r= 0.672;p= 0.006).

Conclusions:

Working memory improvements after Cogmed Working Memory Training disappeared 1 year post training in neonatal extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia survivors. Gains in visuospatial memory persisted 1 year post intervention. Cogmed Working Memory Training may be beneficial for survivors with visuospatial memory deficits.
INJECTION FREQUENCY OF AFLIBERCEPT VERSUS RANIBIZUMAB IN A TREAT-AND-EXTEND REGIMEN FOR CENTRAL RETINAL VEIN OCCLUSION
Authors: Casselholm de Salles Manuel , Amrén Urban , Kvanta Anders , Epstein David L.
Published: April 2018

Purpose:

To prospectively investigate the injection frequency of aflibercept and ranibizumab in the treatment of macular edema in central retinal vein occlusion.

Methods:

Patients with treatment-naive central retinal vein occlusion and macular edema were randomized to receive intravitreal injections with aflibercept (n = 22) or ranibizumab (n = 23) in a treat-and-extend regimen with a follow-up time of 18 months. After 3 loading doses, the treatment intervals were extended by 2 weeks to a maximum of 12 weeks. Intervals were shortened by 2 weeks if macular edema recurred.

Results:

The number of injections was significantly lower in the aflibercept group with a mean of 10.9 injections (95% confidence interval, 9.6–12.3) compared with 14.4 in the ranibizumab group (95% confidence interval 12.7–16.1) at study completion (P = 0.0017). The mean treatment interval was significantly longer in the aflibercept group compared with the ranibizumab group 10.0 (95% confidence interval, 8.7–11.3) and 6.6 (95% confidence interval, 5.2–8.0) weeks, respectively (P < 0.001). No significant difference between the groups regarding visual acuity or central retinal thickness was observed.

Conclusion:

Patients with macular edema secondary to central retinal vein occlusion required significantly fewer intravitreal injections of aflibercept compared with ranibizumab when treated with a treat-and-extend regimen. This may reduce the treatment burden and, to some extent, the need for close monitoring of patients.
Viscoelastic Tamponade Applied to the Ocular Surface for Enhanced Control of Gaseous Egress From the Anterior Chamber During Final Bubble Titration in DMEK Surgery: The “Polite” Burp
Authors: Sales Christopher S. , Fernandez Ana Alzaga , Anwar Zane
Published: April 2018

Purpose:

To present a novel technique for enhancing the surgeon's control over the volume of air or gas that is “burped” from the anterior chamber during final bubble and intraocular pressure (IOP) titration in Descemet membrane endothelial keratoplasty.

Methods:

After ascertaining that the intracameral bubble is either too large and/or has rendered IOP too high, a bead of ophthalmic viscoelastic is applied to the ocular surface over a paracentesis incision, which is then depressed in the usual fashion to burp gas from the anterior chamber.

Results:

The weight and viscosity of the viscoelastic create a tamponade that slows the egress of gas from the anterior chamber, thereby making it more controllable.

Conclusions:

If the bubble size or IOP needs to be reduced at the conclusion of the Descemet membrane endothelial keratoplasty procedure, application of ophthalmic viscoelastic over the paracentesis can enhance the surgeon's control over the volume of gas burped from the anterior chamber, thereby reducing the tendency to swing between a bubble that is too large or too small.
Neural pathways in medial septal cholinergic modulation of chronic pain: distinct contribution of the anterior cingulate cortex and ventral hippocampus
Authors: Jiang Ying-Ying , Shao Shan , Zhang Yu , Zheng Jie , Chen Xi , Cui Shuang , Liu Feng-Yu , Wan You , Yi Ming
Published: April 2018

One specific behavior can be synergistically modulated by different neural pathways. Medial septal (MS) cholinergic system innervates widespread cortical and subcortical regions and participates in pain modulation, but the underlying neural pathways are not fully understood. This study examined the contribution of MS cholinergic neurons and 2 neural pathways: MS–rostral anterior cingulate cortex (rACC) and MS–ventral hippocampal CA1 (vCA1), in modulating perceptual and affective pain behaviors in a mouse model of chronic inflammatory pain. We found that chronic pain activated MS cholinergic neurons and pyramidal neurons in the rACC, but suppressed pyramidal neuronal activities in the vCA1, all of which contributed to the maintenance of pathological pain. Chemogenetic inhibition of MS cholinergic neurons or the MS–rACC pathway inhibited rACC pyramidal neuronal activities and attenuated perceptual and affective dimensions of chronic pain. By contrast, chemogenetic activation of MS cholinergic neurons also produced analgesia, but by rescuing hypofunctional pyramidal neurons in vCA1. These results clearly demonstrate that the MS cholinergic system differentially modulates chronic inflammatory pain through MS–rACC or MS–vCA1 pathways. More significantly, our research provides evidence for a novel paradigm of neural circuit modulation: MS cholinergic inhibition and activation induce similar analgesia but through distinct neural pathways.
β-Blocker therapy for cirrhotic cardiomyopathy: a randomized-controlled trial
Authors: Silvestre Odilson M. , Farias Alberto Q. , Ramos Danusa S. , Furtado Meive S. , Rodrigues Ana C. , Ximenes Rafael O. , de Campos Mazo Daniel F. , Yoshimura Zitelli Patricia M. , Diniz Marcio A. , Andrade José L. , Strunz Celia , Friedmann Antônio A. , Lee Samuel S. , Carrilho Flair J. , D’Albuquerque Luiz A.C. , Bacal Fernando
Published: April 2018

Background

Cirrhotic cardiomyopathy is characterized by an attenuated contractile response to stress. Long-term exposure of β-adrenergic receptors to persistently high levels of catecholamines has been implicated in its pathogenesis. We hypothesized that β-blockade with metoprolol could reverse the changes in heart function and morphology in cirrhotic cardiomyopathy.

Patients and methods

In this prospective randomized trial, we included 78 patients aged between 18 and 60 years with abnormal cardiac output response under dobutamine stress echocardiography, without primary cardiac disease or a history of alcohol intake. Patients were assigned randomly to receive metoprolol or placebo for 6 months. The primary endpoint was the improvement in cardiac output response to stress, measured by an increase in the left ventricle stroke volume more than 30%.

Results

Three (7.3%) patients in the metoprolol group and nine (24.3%) patients in the placebo group showed improved stroke volume (P=0.057). Diastolic dysfunction was found in two (4.8%) patients before and in five (15.6%) patients after therapy in the metoprolol group, and in 10 (27%) patients before and nine (31%) patients after therapy in the placebo group (P=0.67). After treatment, no echocardiography parameter of morphology was significantly different between metoprolol or placebo groups. No significant differences were observed in noradrenaline, plasma renin activity, and troponin levels between groups. Cirrhosis-related clinical events, including hospitalizations and mortality, were not significantly different between the two groups. Six months of therapy with β-blocker did not ameliorate heart function and morphology in patients with cirrhotic cardiomyopathy.