bluuebunny/crossref_metadata_2025 huggingface dataset:
Report on milestones for care and support under the U.S. National Plan to Address Alzheimer's Disease
Authors:   Alzheimer's Association National Plan Care and Support Milestone Workgroup, Borson Soo , Boustani Malaz A. , Buckwalter Kathleen C. , Burgio Louis D. , Chodosh Joshua , Fortinsky Richard H. , Gifford David R. , Gwyther Lisa P. , Koren Mary Jane , Lynn Joanne , Phillips Cheryl , Roherty Martha , Ronch Judah , Stahl Claudia , Rodgers Lauren , Kim Hye , Baumgart Matthew , Geiger Angela
Published: February 2016

Introduction

Under the U.S. national Alzheimer's plan, the National Institutes of Health identified milestones required to meet the plan's biomedical research goal (Goal 1). However, similar milestones have not been created for the goals on care (Goal 2) and support (Goal 3).

Methods

The Alzheimer's Association convened a workgroup with expertise in clinical care, long‐term services and supports, dementia care and support research, and public policy. The workgroup reviewed the literature on Alzheimer's care and support; reviewed how other countries are addressing the issue; and identified public policies needed over the next 10 years to achieve a more ideal care and support system.

Results

The workgroup developed and recommended 73 milestones for Goal 2 and 56 milestones for Goal 3.

Discussion

To advance the implementation of the U.S. national Alzheimer's plan, the U.S. government should adopt these recommended milestones, or develop similar milestones, to be incorporated into the national plan.
Alternative approach for management of an electrical storm in Brugada syndrome: Importance of primary ablation within a narrow time window
Authors: Talib Ahmed Karim , Yui Yoshiaki , Kaneshiro Takashi , Sekiguchi Yukio , Nogami Akihiko , Aonuma Kazutaka
Published: February 2016

Placement of an implantable cardioverter–defibrillator (ICD) is the only powerful treatment modality for Brugada syndrome in patients presenting with ventricular fibrillation (VF). For those whose first presentation is an electrical storm, pharmacologic therapy is typically used to control VF followed by ICD implantation. We report an alternative approach whereby, before ICD implantation, emergency catheter ablation of the VF‐triggering premature ventricular contraction (PVC) resulted in long‐term VF‐free survival. The results suggest that, because VF triggers appear in a narrow time window, ablation of the culprit PVCs that initiate VF before the index PVCs subside is a reasonable alternative approach.
Plate tectonics and mantle plumes as a basis of deep-seated Earth’s tectonic activity for the last 2 Ga
Authors: Kuzmin M.I. , Yarmolyuk V.V.
Published: February 2016

The onset of the modern tectonic style that combines plate-related and plume-related mechanisms has been discussed. Such a tectonic style could have started on the Earth when all layers of our planet had formed. Analysis of available geological data shows that the solid inner core crystallized by 2.7 Ga. Typical geologic complexes appeared on the continents as a result of plate tectonics processes at that time. The layer D″ that accumulates lithospheric slabs, which do not remain at the upper-lower mantle interface but can go down to the core-mantle boundary, was finally produced by 2 Ga. At pressures and temperatures of the D″ layer perovskite, a principal mineral of the lower mantle transforms into postperovskite phase. The isotope data suggest the existence of mantle (EM-I and EM-II) domains, being the sources for oceanic island basalts (OIB) and the depleted upper mantle (asthenosphere), the source for mid-ocean ridge basalts (MORB), from at least 2 Ga. It is accepted that the recent tectonic style started on the Earth at that period. Deep-seated processes suggest the involvement of all Earth’s layers. The asthenosphere–lithosphere interaction is responsible for different types of large surface structures that develop as fold mountains, oceanic spaces, and subduction zones. The descending lithospheric slabs (cold mantle material) and ascending mantle material in hot mantle provinces or the so-called low shear velocity provinces are responsible for the lower mantle convection. The plume is produced in the layer D″, which accumulates the descending lithosphere slabs as well as light elements released from the outer liquid core, which are oxidized in this layer, thus resulting in thermochemical plume formation. At the same time the molten ferric iron penetrates the core. So, we see the interaction of all Earth’s layers. The article also considers the evolutionary history of the Siberian continent over 700 Myr as early as the breakdown of Rodinia and the formation of mountain folds and rifting structures and the associated metallogeny.
Composition of the Earth’s core: A review
Authors: Litasov K.D. , Shatskiy A.F.
Published: February 2016

This paper provides the state-of-the-art discussion of major aspects of the composition and evolution of the Earth’s core. A comparison of experimentally-derived density of Fe with seismological data shows that the outer liquid core has a homogeneous structure and a ~10% density deficit, whereas the solid inner core has a complex heterogeneous anisotropic structure and a ~5% density deficit. Recent estimations of the core-mantle boundary (CMB) and inner core boundary temperatures are equal to 3800–4200 K and 5200–5700 K, respectively. Si and O (up to 5–7 wt.%) are considered to be the most likely light element candidates in the liquid core. Cosmochemical estimates show that the core must contain about 2 wt.% S and new experimental data indicate that the inner core structure gives the best match to the properties of Fe carbides. Our best estimate of the Earth’s core calls for 5–6 wt.% Si, 0.5–1.0 wt.% O, 1.8–1.9 wt.% S, and 2.0 wt.% C, with the Fe7C3 carbide being the dominant phase in the inner core. The study of short-lived isotope systems shows that the core could have formed early in the Earth’s history within about 30–50 Myr after the formation of the Solar System, t0 = 4567.2 ± 0.5 Ma. Studies on the partitioning of siderophile elements between liquid iron and silicate melt suggest that the core material would be formed in a magma ocean at ~1000–1500 km depths and 3000–4000 K. The oxygen fugacity for the magma ocean is estimated to vary from 4–5 to 1–2 log units below the Iron-Wustite oxygen buffer. However, the data for Mo, W, and S suggest addition of a late veneer of 10–15% of oxidized chondritic material as a result of the Moon-forming giant impact. Thermal and energetics core models agree with the estimate of a mean CMB heat flow of 7–17 TW. The excess heat is transported out of the core via two large low shear velocity zones at the base of superplumes. These zones may not be stable in their positions over geologic time and could move according to cycles of mantle plume and plate tectonics. The CMB heat fluxes are controlled either by high heat production from the core or subduction of cold slabs, but in both cases are closely linked with surface geodynamic processes and plate tectonic motions. Considerable amounts of exchange may have occurred between the core and mantle early in the Earth’s history even up to the formation of a basal magma ocean. However, the extent of material exchange across the CMB upon cooling of the mantle was no greater than 1–2% of the core’s mass, which, however, was sufficient to supply thermochemical plumes with volatiles H, C, and S.
Neoproterozoic tectonic structure of the Yenisei Ridge and formation of the western margin of the Siberian craton based on new geological, paleomagnetic, and geochronological data
Authors: Vernikovsky V.A. , Metelkin D.V. , Vernikovskaya A.E. , Matushkin N.Yu. , Kazansky A.Yu. , Kadilnikov P.I. , Romanova I.V. , Wingate M.T.D. , Larionov A.N. , Rodionov N.V.
Published: February 2016

There are continuing issues concerning the formation and reconstruction of the geographic position of the Neoproterozoic Yenisei Ridge—a key element of the western framing of the Siberian craton and the Central Asian orogenic belt. This study focuses on the inner structure, composition, and boundaries of the Central Angara terrane, which is the largest in the Transangarian segment of the Yenisei Ridge. We propose a scheme of fault deformation of the region and demonstrate that the fault tectonics of the Central Angara terrane is distinct from that of adjacent terranes. We study in detail the Yeruda pluton granitoids of the Teya complex, which indicate accretionary-collisional magmatic events in this terrane prior to its collision with Siberia. New geochemistry and SHRIMP U–Th–Pb zircon geochronology of the granites indicate that they formed at 880–860 Ma in a collisional setting. Integrated petromagnetic and paleomagnetic investigations yield a paleomagnetic pole that is significantly different from the corresponding Neoproterozoic interval of the apparent polar wander path (APWP) for Siberia. The difference in paleolatitudes between the Central Angara terrane and the Siberian craton at the time of the Teya granites formation was at least 8.6 degrees, which equals a latitudinal separation of at least 1000 km. We consider various possible positions for the terrane relative to the Siberian craton. These results demonstrate that the 880–860 Ma magmatic events in the Central Angara terrane are not related to events in the western margin of the Siberian craton. Therefore, they do not indicate the existence of a Grenville-age orogenic belt in this location, as proposed by some authors.
Evidence for a subduction component in the diamond-bearing mantle of the Siberian craton
Authors: Shatsky V.S. , Zedgenizov D.A. , Ragozin A.L.
Published: February 2016

Evidence for the involvement of a subduction component in diamond formation is analyzed based on literature data and our studies. Examination of xenoliths of diamondiferous eclogites, including X-ray tomography analysis, testifies to the superposed character of most diamonds. Diamond generation is accompanied by the serious modification of eclogite substratum. Isotope–geochemical data show that the eclogites originated from oceanic-crust rocks. The oxygen isotope compositions of garnets and clinopyroxenes from websterite xenoliths are similar to the mantle average (5.3–5.6‰). The eclogite minerals vary considerably in oxygen isotope composition (δ18O of 5.3 to 12.4‰). Diamonds of eclogitic paragenesis predominate dramatically in the placers of the northeastern Yakutian diamondiferous province. In placer eclogitic diamonds, δ13C varies from − 27.2 to − 3‰ (n = 28). In diamonds of ultrabasic paragenesis, the range of δ13C values is much narrower (from − 7.1 to − 0.5‰). All diamonds of variety V have a lighter carbon isotope composition (from − 24.1 to − 17.4‰). In a wide range of crystals with a contrasting carbon isotope composition, the isotope composition of the rim tends toward the average mantle value. This suggests that the eclogitic diamonds grew first with the participation of carbon from subducted continental crust and finally with the involvement of mantle carbon.
A Pilot Placebo Controlled Randomized Trial of Dexamethasone for Chronic Subdural Hematoma
Authors: Prud’homme Michel , Mathieu François , Marcotte Nicolas , Cottin Sylvine
Published: February 2016

Background: Current opinions regarding the use of dexamethasone in the treatment of chronic subdural hematomas (CSDH) are only based on observational studies. Moreover, the use of corticosteroids in asymptomatic or minimally symptomatic patient with this condition remains controversial. Here, we present data from a prospective randomized pilot study of CSDH patients treated with dexamethasone or placebo. Methods: Twenty patients with imaging-confirmed CSDH were recruited from a single center and randomized to receive dexamethasone (12 mg/day for 3 weeks followed by tapering) or placebo as a conservative treatment. Patients were followed for 6 months and the rate of success of conservative treatment with dexamethasone versus placebo was measured. Parameters such as hematoma thickness and clinical changes were also compared before and after treatment with chi-square tests. Adverse events and complications were documented. Results: During the 6-month follow-up, one of ten patients treated with corticosteroids had to undergo surgical drainage and three of ten patients were treated surgically after placebo treatment. At the end of the study, all remaining patients had complete radiological resolution. No significant differences were observed in terms of hematoma thickness profile and impression of change; however, patients experienced more severe side effects when treated with steroids as compared with placebo. Dexamethasone contributed to many serious adverse events. Conclusions: Given the small sample size, these preliminary results have not shown a clear beneficial effect of dexamethasone against placebo in our patients. However, the number of secondary effects reported was much greater for corticosteroids, and dexamethasone treatment was responsible for significant complications.
Stiffness analysis and comparison of a Biglide parallel grinder with alternative spatial modular parallelograms
Authors: Wu Guanglei , Zou Ping
Published: February 2016

This paper deals with the stiffness modeling, analysis and comparison of a Biglide parallel grinder with two alternative modular parallelograms. It turns out that the Cartesian stiffness matrix of the manipulator has the property that it can be decoupled into two homogeneous matrices, corresponding to the translational and rotational aspects, through which the principal stiffnesses and the associated directions are identified by means of the eigenvalue problem, allowing the evaluation of the translational and rotational stiffness of the manipulator either at a given pose or the overall workspace. The stiffness comparison of the two alternative Biglide machines reveals the (dis)advantages of the two different spatial modular parallelograms.
IV. Plato and Politics
Authors: Findlay J. N.
Published: February 2016

Plato is best regarded as having constructed an imaginary Pythagorean commune, hanging in the pure ether of hypothesis, in order to show how political life derives from the metaphysical Ultimates of the Universe, and how the same Unity which everywhere disciplines variety into excellence and limit and expresses itself in cosmic and individual life, soul and mind, is also expressed in the mutual regard that different individuals and different groups of individuals have for one another in an ordered social whole.

But this view is not tenable unless one is ready to regard all Western political thought as mistaken. For when Aquinas adapted the basic concepts of Aristotle’s Politics to medieval Christianity and to Christendom, he was taking over Plato’s thought, although in a reduced form. Findlay removes all real concern for human institutions from Plato. Moreover, Augustine’s conception of two cities, one of them heavenly, remained in Europe as a vision, to supplement what Aristotle had reduced and Aquinas had codified.
Ionic polarization-induced current–voltage hysteresis in CH3NH3PbX3 perovskite solar cells
Authors: Meloni Simone , Moehl Thomas , Tress Wolfgang , Franckevičius Marius , Saliba Michael , Lee Yong Hui , Gao Peng , Nazeeruddin Mohammad Khaja , Zakeeruddin Shaik Mohammed , Rothlisberger Ursula , Graetzel Michael
Published: February 2016

CH3NH3PbX3 (MAPbX3) perovskites have attracted considerable attention as absorber materials for solar light harvesting, reaching solar to power conversion efficiencies above 20%. In spite of the rapid evolution of the efficiencies, the understanding of basic properties of these semiconductors is still ongoing. One phenomenon with so far unclear origin is the so-called hysteresis in the current–voltage characteristics of these solar cells. Here we investigate the origin of this phenomenon with a combined experimental and computational approach. Experimentally the activation energy for the hysteretic process is determined and compared with the computational results. First-principles simulations show that the timescale for MA+ rotation excludes a MA-related ferroelectric effect as possible origin for the observed hysteresis. On the other hand, the computationally determined activation energies for halide ion (vacancy) migration are in excellent agreement with the experimentally determined values, suggesting that the migration of this species causes the observed hysteretic behaviour of these solar cells.
Experimental control of transport resonances in a coherent quantum rocking ratchet
Authors: Grossert Christopher , Leder Martin , Denisov Sergey , Hänggi Peter , Weitz Martin
Published: February 2016

The ratchet phenomenon is a means to get directed transport without net forces. Originally conceived to rectify stochastic motion and describe operational principles of biological motors, the ratchet effect can be used to achieve controllable coherent quantum transport. This transport is an ingredient of several perspective quantum devices including atomic chips. Here we examine coherent transport of ultra-cold atoms in a rocking quantum ratchet. This is realized by loading a rubidium atomic Bose–Einstein condensate into a periodic optical potential subjected to a biharmonic temporal drive. The achieved long-time coherence allows us to resolve resonance enhancement of the atom transport induced by avoided crossings in the Floquet spectrum of the system. By tuning the strength of the temporal modulations, we observe a bifurcation of a single resonance into a doublet. Our measurements reveal the role of interactions among Floquet eigenstates for quantum ratchet transport.
Single crystal functional oxides on silicon
Authors: Bakaul Saidur Rahman , Serrao Claudy Rayan , Lee Michelle , Yeung Chun Wing , Sarker Asis , Hsu Shang-Lin , Yadav Ajay Kumar , Dedon Liv , You Long , Khan Asif Islam , Clarkson James David , Hu Chenming , Ramesh Ramamoorthy , Salahuddin Sayeef
Published: February 2016

Single-crystalline thin films of complex oxides show a rich variety of functional properties such as ferroelectricity, piezoelectricity, ferro and antiferromagnetism and so on that have the potential for completely new electronic applications. Direct synthesis of such oxides on silicon remains challenging because of the fundamental crystal chemistry and mechanical incompatibility of dissimilar interfaces. Here we report integration of thin (down to one unit cell) single crystalline, complex oxide films onto silicon substrates, by epitaxial transfer at room temperature. In a field-effect transistor using a transferred lead zirconate titanate layer as the gate insulator, we demonstrate direct reversible control of the semiconductor channel charge with polarization state. These results represent the realization of long pursued but yet to be demonstrated single-crystal functional oxides on-demand on silicon.
Shaping metallic glasses by electromagnetic pulsing
Authors: Kaltenboeck Georg , Demetriou Marios D. , Roberts Scott , Johnson William L.
Published: February 2016

With damage tolerance rivalling advanced engineering alloys and thermoplastic forming capabilities analogous to conventional plastics, metallic glasses are emerging as a modern engineering material. Here, we take advantage of their unique electrical and rheological properties along with the classic Lorentz force concept to demonstrate that electromagnetic coupling of electric current and a magnetic field can thermoplastically shape a metallic glass without conventional heating sources or applied mechanical forces. Specifically, we identify a process window where application of an electric current pulse in the presence of a normally directed magnetic field can ohmically heat a metallic glass to a softened state, while simultaneously inducing a large enough magnetic body force to plastically shape it. The heating and shaping is performed on millisecond timescales, effectively bypassing crystallization producing fully amorphous-shaped parts. This electromagnetic forming approach lays the groundwork for a versatile, time- and energy-efficient manufacturing platform for ultrastrong metals.
Oriented Nucleation of both Ge-Fresnoite and Benitoite/BaGe4O9 during the Surface Crystallisation of Glass Studied by Electron Backscatter Diffraction
Authors: Wisniewski Wolfgang , Patschger Marek , Murdzheva Steliana , Thieme Christian , Rüssel Christian
Published: February 2016

Two glasses of the compositions 2 BaO - TiO2 - 2.75 GeO2 and 2 BaO – TiO2 –3.67 GeO2 (also known as BTG55) are annealed at temperatures from 680 to 970 °C to induce surface crystallization. The resulting samples are analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM) including electron backscatter diffraction (EBSD). Ge-Fresnoite (Ba2TiGe2O8, BTG) is observed at the immediate surface of all samples and oriented nucleation is proven in both compositions. After a very fast kinetic selection, the crystal growth of BTG into the bulk occurs via highly oriented dendrites where the c-axes are oriented perpendicular to the surface. The growth of this oriented layer is finally blocked by dendritc BTG originating from bulk nucleation. The secondary phases BaTiGe3O9 (benitoite) and BaGe4O9 are also identified near the surface by XRD and localized by EBSD which additionally indicates orientation preferences for these phases. This behaviour is in contrast with previous reports from the Ba2TiSi2O8 as well as the Sr2TiSi2O8 systems.
Brain zinc chelation by diethyldithiocarbamate increased the behavioral and mitochondrial damages in zebrafish subjected to hypoxia
Authors: Braga Marcos M. , Silva Emerson S. , Moraes Tarsila B. , Schirmbeck Gabriel Henrique , Rico Eduardo P. , Pinto Charles B. , Rosemberg Denis B. , Dutra-Filho Carlos S. , Dias Renato D. , Oliveira Diogo L. , T. Rocha João Batista , Souza Diogo O.
Published: February 2016

The increase in brain levels of chelatable zinc (Zn) in dysfunctions involving oxygen deprivation has stimulated the treatment with Zn chelators, such as diethyldithiocarbamate (DEDTC). However, DEDTC is a redox-active compound and it should be better evaluated during hypoxia. We use the hypoxia model in zebrafish to evaluate DEDTC effects. The exploratory behavior, chelatable Zn content, activities of mitochondrial dehydrogenases, reactive species levels (nitric oxide, superoxide anion, hydroxyl radical scavenger capacity) and cellular antioxidants (sulfhydryl, superoxide dismutase) of zebrafish brain were assessed after recovery, with or without 0.2 mM DEDTC. The increased brain levels of chelatable Zn induced by hypoxia were mitigated by DEDTC. However, the novel tank task indicated that DEDTC did further enhance the exploratory deficit caused by hypoxia. Furthermore, these behavioral impairments caused by DEDTC were more associated with a negative action on mitochondrial activity and brain oxidative balance. Thus, due to apparent pro-oxidant action of DEDTC, our data do not support its use for neuroprotection in neuropathologies involving oxygen deprivation.
The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1
Authors: Abella Vanessa , Scotece Morena , Conde Javier , López Verónica , Pirozzi Claudio , Pino Jesús , Gómez Rodolfo , Lago Francisca , González-Gay Miguel Ángel , Gualillo Oreste
Published: February 2016

Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1β (IL1β) stimulates several mediators of cartilage degradation. Toll like receptor-4 (TLR4) can bind to various damage-associated molecular patterns, leading to inflammatory condition. So far, no data exist of PGRN effects in inflammatory conditions induced by IL1β or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1β- or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1β or LPS. First, we showed that recombinant PGRN had no effects on cell viability. We present evidence that PGRN expression was increased during the differentiation of ATDC-5 cell line. Moreover, PGRN mRNA and protein expression is increased in cartilage, synovial and infrapatellar fat pad tissue samples from OA patients. PGRN mRNA levels are upregulated under TNFα and IL1β stimulation. Our data showed that PGRN is able to significantly counteract the IL1β-induced expression of NOS2, COX2, MMP13 and VCAM-1. LPS-induced expression of NOS2 is also decreased by PGRN. These effects are mediated, at least in part, through TNFR1. Taken together, our results suggest that PGRN has a clear anti-inflammatory function.
Differentially pumped spray deposition as a rapid screening tool for organic and perovskite solar cells
Authors: Jung Yen-Sook , Hwang Kyeongil , Scholes Fiona H. , Watkins Scott E. , Kim Dong-Yu , Vak Doojin
Published: February 2016

We report a spray deposition technique as a screening tool for solution processed solar cells. A dual-feed spray nozzle is introduced to deposit donor and acceptor materials separately and to form blended films on substrates in situ. Using a differential pump system with a motorised spray nozzle, the effect of film thickness, solution flow rates and the blend ratio of donor and acceptor materials on device performance can be found in a single experiment. Using this method, polymer solar cells based on poly(3-hexylthiophene) (P3HT):(6,6)-phenyl C61 butyric acid methyl ester (PC61BM) are fabricated with numerous combinations of thicknesses and blend ratios. Results obtained from this technique show that the optimum ratio of materials is consistent with previously reported values confirming this technique is a very useful and effective screening method. This high throughput screening method is also used in a single-feed configuration. In the single-feed mode, methylammonium iodide solution is deposited on lead iodide films to create a photoactive layer of perovskite solar cells. Devices featuring a perovskite layer fabricated by this spray process demonstrated a power conversion efficiencies of up to 7.9%.
Colonic Fermentation Promotes Decompression sickness in Rats
Authors: de Maistre Sébastien , Vallée Nicolas , Gempp Emmanuel , Lambrechts Kate , Louge Pierre , Duchamp Claude , Blatteau Jean-Eric
Published: February 2016

Massive bubble formation after diving can lead to decompression sickness (DCS). During dives with hydrogen as a diluent for oxygen, decreasing the body’s H2 burden by inoculating hydrogen-metabolizing microbes into the gut reduces the risk of DCS. So we set out to investigate if colonic fermentation leading to endogenous hydrogen production promotes DCS in fasting rats. Four hours before an experimental dive, 93 fasting rats were force-fed, half of them with mannitol and the other half with water. Exhaled hydrogen was measured before and after force-feeding. Following the hyperbaric exposure, we looked for signs of DCS. A higher incidence of DCS was found in rats force-fed with mannitol than in those force-fed with water (80%, [95%CI 56, 94] versus 40%, [95%CI 19, 64], p < 0.01). In rats force-fed with mannitol, metronidazole pretreatment reduced the incidence of DCS (33%, [95%CI 15, 57], p = 0.005) at the same time as it inhibited colonic fermentation (14 ± 35 ppm versus 118 ± 90 ppm, p = 0.0001). Pre-diveingestion of mannitol increased the incidence of DCS in fasting rats when colonic fermentation peaked during the decompression phase. More generally, colonic fermentation in rats on a normal diet could promote DCS through endogenous hydrogen production.
Changes in heterosubtypic antibody responses during the first year of the 2009 A(H1N1) influenza pandemic
Authors: Freidl Gudrun S. , van den Ham Henk-Jan , Boni Maciej F. , de Bruin Erwin , Koopmans Marion P.G.
Published: February 2016

Seropositivity to avian influenza (AI) via low-level antibody titers has been reported in the general population and poultry-exposed individuals, raising the question whether these findings reflect true infection with AI or cross-reactivity. Here we investigated serological profiles against human and avian influenza viruses in the general population using a protein microarray platform. We hypothesized that higher antibody diversity across recent H1 and H3 influenza viruses would be associated with heterosubtypic reactivity to older pandemic- and AI viruses. We found significant heterogeneity in antibody profiles. Increased antibody diversity to seasonal influenza viruses was associated with low-level heterosubtypic antibodies to H9 and H7, but not to H5 AI virus. Individuals exposed to the recent 2009 A(H1N1) pandemic showed higher heterosubtypic reactivity. We show that there is a complex interplay between prior exposures to seasonal and recent pandemic influenza viruses and the development of heterosubtypic antibody reactivity to animal influenza viruses.
Bioluminescent imaging of ABCG2 efflux activity at the blood-placenta barrier
Authors: Kumar Jeyan S. , Wei Bih-Rong , Madigan James P. , Simpson R. Mark , Hall Matthew D. , Gottesman Michael M.
Published: February 2016

Physiologic barriers such as the blood placenta barrier (BPB) and the blood brain barrier protect the underlying parenchyma from pathogens and toxins. ATP-binding cassette (ABC) transporters are transmembrane proteins found at these barriers and function to efflux xenobiotics and maintain chemical homeostasis. Despite the plethora of ex vivo and in vitro data showing the function and expression of ABC transporters, no imaging modality exists to study ABC transporter activity in vivo at the BPB. In the present study, we show that in vitro models of the placenta possess ABCG2 activity and can specifically transport D-luciferin, the endogenous substrate of firefly luciferase. To test ABCG2 transport activity at the BPB, we devised a breeding strategy to generate a bioluminescent pregnant mouse model to demonstrate transporter function in vivo. We found that coadministering the ABCG2 inhibitors Ko143 and gefitinib with D-luciferin increased bioluminescent signal from fetuses and placentae, whereas the control P-gp inhibitor DCPQ had no effect. We believe that our bioluminescent pregnant mouse model will facilitate greater understanding of the BPB and ABCG2 activity in health and disease.
A Novel PET Imaging Probe for the Detection and Monitoring of Translocator Protein 18 kDa Expression in Pathological Disorders
Authors: Perrone Mara , Moon Byung Seok , Park Hyun Soo , Laquintana Valentino , Jung Jae Ho , Cutrignelli Annalisa , Lopedota Angela , Franco Massimo , Kim Sang Eun , Lee Byung Chul , Denora Nunzio
Published: February 2016

A new fluorine-substituted ligand, compound 1 (CB251), with a very high affinity (Ki = 0.27 ± 0.09 nM) and selectivity for the 18-kDa translocator protein (TSPO), is presented as an attractive biomarker for the diagnosis of neuroinflammation, neurodegeneration and tumour progression. To test compound 1 as a TSPO PET imaging agent in vivo, 2-(2-(4-(2-[18F]fluoroethoxy)phenyl)-6,8-dichloroimidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide ([18F]1; [18F]CB251) was synthesized by nucleophilic aliphatic substitution in a single-step radiolabelling procedure with a 11.1 ± 3.5% (n = 14, decay corrected) radiochemical yield and over 99% radiochemical purity. In animal PET imaging studies, [18F]CB251 provided a clearly visible image of the inflammatory lesion with the binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND 1.83 ± 0.18), in a neuroinflammation rat model based on the unilateral stereotaxic injection of lipopolysaccharide (LPS), comparable to that of [11C]PBR28 (BPND 1.55 ± 0.41). [18F]CB251 showed moderate tumour uptake (1.96 ± 0.11%ID/g at 1 h post injection) in human glioblastoma U87-MG xenografts. These results suggest that [18F]CB251 is a promising TSPO PET imaging agent for neuroinflammation and TSPO-rich cancers.
Transcription Factor RFX2 Is a Key Regulator of Mouse Spermiogenesis
Authors: Wu Yujian , Hu Xiangjing , Li Zhen , Wang Min , Li Sisi , Wang Xiuxia , Lin Xiwen , Liao Shangying , Zhang Zhuqiang , Feng Xue , Wang Si , Cui Xiuhong , Wang Yanling , Gao Fei , Hess Rex A. , Han Chunsheng
Published: February 2016

The regulatory factor X (RFX) family of transcription factors is crucial for ciliogenesis throughout evolution. In mice, Rfx1-4 are highly expressed in the testis where flagellated sperm are produced, but the functions of these factors in spermatogenesis remain unknown. Here, we report the production and characterization of the Rfx2 knockout mice. The male knockout mice were sterile due to the arrest of spermatogenesis at an early round spermatid step. The Rfx2-null round spermatids detached from the seminiferous tubules, forming large multinucleated giant cells that underwent apoptosis. In the mutants, formation of the flagellum was inhibited at its earliest stage. RNA-seq analysis identified a large number of cilia-related genes and testis-specific genes that were regulated by RFX2. Many of these genes were direct targets of RFX2, as revealed by chromatin immunoprecipitation-PCR assays. These findings indicate that RFX2 is a key regulator of the post-meiotic development of mouse spermatogenic cells.
Correction: Corrigendum: Epigenetic silencing of the XAF1 gene is mediated by the loss of CTCF binding
Authors: Victoria-Acosta Georgina , Vazquez-Santillan Karla , Jimenez-Hernandez Luis , Muñoz-Galindo Laura , Maldonado Vilma , Martinez-Ruiz Gustavo Ulises , Melendez-Zajgla Jorge
Published: February 2016

XAF1 is a tumour suppressor gene that compromises cell viability by modulating different cellular events such as mitosis, cell cycle progression and apoptosis. In cancer, the XAF1 gene is commonly silenced by CpG-dinucleotide hypermethylation of its promoter. DNA demethylating agents induce transcriptional reactivation of XAF1, sensitizing cancer cells to therapy. The molecular mechanisms that mediate promoter CpG methylation have not been previously studied. Here, we demonstrate that CTCF interacts with the XAF1 promoter in vivo in a methylation-sensitive manner. By transgene assays, we demonstrate that CTCF mediates the open-chromatin configuration of the XAF1 promoter, inhibiting both CpG-dinucleotide methylation and repressive histone posttranslational modifications. In addition, the absence of CTCF in the XAF1 promoter inhibits transcriptional activation induced by well-known apoptosis activators. We report for the first time that epigenetic silencing of the XAF1 gene is a consequence of the loss of CTCF binding.
Comparative analyses of fungicide sensitivity and SSR marker variations indicate a low risk of developing azoxystrobin resistance in Phytophthora infestans
Authors: Qin Chun-Fang , He Meng-Han , Chen Feng-Ping , Zhu Wen , Yang Li-Na , Wu E-Jiao , Guo Zheng-Liang , Shang Li-Ping , Zhan Jiasui
Published: February 2016

Knowledge of the evolution of fungicide resistance is important in securing sustainable disease management in agricultural systems. In this study, we analyzed and compared the spatial distribution of genetic variation in azoxystrobin sensitivity and SSR markers in 140 Phytophthora infestans isolates sampled from seven geographic locations in China. Sensitivity to azoxystrobin and its genetic variation in the pathogen populations was measured by the relative growth rate (RGR) at four fungicide concentrations and determination of the effective concentration for 50% inhibition (EC50). We found that all isolates in the current study were sensitive to azoxystrobin and their EC50 was similar to that detected from a European population about 20 years ago, suggesting the risk of developing azoxystrobin resistance in P. infestans populations is low. Further analyses indicate that reduced genetic variation and high fitness cost in resistant mutations are the likely causes for the low evolutionary likelihood of developing azoxystrobin resistance in the pathogen. We also found a negative correlation between azoxystrobin tolerance in P. infestans populations and the mean annual temperature of collection sites, suggesting that global warming may increase the efficiency of using the fungicide to control the late blight.
Novel Osteogenic Ti-6Al-4V Device For Restoration Of Dental Function In Patients With Large Bone Deficiencies: Design, Development And Implementation
Authors: Cohen D. J. , Cheng A. , Kahn A. , Aviram M. , Whitehead A. J. , Hyzy S. L. , Clohessy R. M. , Boyan B. D. , Schwartz Z.
Published: February 2016

Custom devices supporting bone regeneration and implant placement are needed for edentulous patients with large mandibular deficiencies where endosteal implantation is not possible. We developed a novel subperiosteal titanium-aluminum-vanadium bone onlay device produced by additive manufacturing (AM) and post-fabrication osteogenic micro-/nano-scale surface texture modification. Human osteoblasts produced osteogenic and angiogenic factors when grown on laser-sintered nano-/micro-textured surfaces compared to smooth surfaces. Surface-processed constructs caused higher bone-to-implant contact, vertical bone growth into disk pores (microCT and histomorphometry) and mechanical pull-out force at 5 and 10 w on rat calvaria compared to non surface-modified constructs, even when pre-treating the bone to stimulate osteogenesis. Surface-modified wrap-implants placed around rabbit tibias osseointegrated by 6 w. Finally, patient-specific constructs designed to support dental implants produced via AM and surface-processing were implanted on edentulous mandibular bone. 3 and 8 month post-operative images showed new bone formation and osseointegration of the device and indicated stability of the dental implants.
Sustainability of Transient Kinetic Regimes and Origins of Death
Authors: Zubarev Dmitry Yu. , Pachón Leonardo A.
Published: February 2016

It is generally recognized that a distinguishing feature of life is its peculiar capability to avoid equilibration. The origin of this capability and its evolution along the timeline of abiogenesis is not yet understood. We propose to study an analog of this phenomenon that could emerge in non-biological systems. To this end, we introduce the concept of sustainability of transient kinetic regimes. This concept is illustrated via investigation of cooperative effects in an extended system of compartmentalized chemical oscillators under batch and semi-batch conditions. The computational study of a model system shows robust enhancement of lifetimes of the decaying oscillations which translates into the evolution of the survival function of the transient non-equilibrium regime. This model does not rely on any form of replication. Rather, it explores the role of a structured effective environment as a contributor to the system-bath interactions that define non-equilibrium regimes. We implicate the noise produced by the effective environment of a compartmentalized oscillator as the cause of the lifetime extension.
Serological Evaluation of Immunity to the Varicella-Zoster Virus Based on a Novel Competitive Enzyme-Linked Immunosorbent Assay
Authors: Liu Jian , Ye Xiangzhong , Jia Jizong , Zhu Rui , Wang Lina , Chen Chunye , Yang Lianwei , Wang Yongmei , Wang Wei , Ye Jianghui , Li Yimin , Zhu Hua , Zhao Qinjian , Cheng Tong , Xia Ningshao
Published: February 2016

Varicella-zoster virus (VZV) is a highly contagious agent of varicella and herpes zoster. Varicella can be lethal to immunocompromised patients, babies, HIV patients and other adults with impaired immunity. Serological evaluation of immunity to VZV will help determine which individuals are susceptible and evaluate vaccine effectiveness. A collection of 110 monoclonal antibodies (mAbs) were obtained by immunization of mice with membrane proteins or cell-free virus. The mAbs were well characterized and a competitive sandwich ELISA (capture mAb: 8H6; labelling mAb: 1B11) was established to determine neutralizing antibodies in human serum with reference to the FAMA test. A total of 920 human sera were evaluated. The competitive sandwich ELISA showed a sensitivity of 95.6%, specificity of 99.77% and coincidence of 97.61% compared with the fluorescent-antibody-to-membrane-antigen (FAMA) test. The capture mAb 8H6 was characterized as a specific mAb for VZV ORF9, a membrane-associated tegument protein that interacts with glycoprotein E (gE), glycoprotein B (gB) and glycoprotein C (gC). The labelling mAb 1B11 was characterized as a complement-dependent neutralizing mAb specific for the immune-dominant epitope located on gE, not on other VZV glycoproteins. The established competitive sandwich ELISA could be used as a rapid and high-throughput method for evaluating immunity to VZV.
The relationship between the preoperative plasma level of HIF-1α and clinic pathological features, prognosis in non-small cell lung cancer
Authors: He Jiabei , Hu Ying , Hu Mingming , Zhang Siyi , Li Baolan
Published: February 2016

Studies have found that hypoxia is the most common feature in all of solid tumor progression, thus it has become a central issue in tumor physiology and cancer treatment. Hypoxia-inducible factor-1α (HIF-1α) could make the tumor produce adaptive biological response to hypoxia and become more aggressive. In this paper, we used enzyme linked immune sorbent assay to detect the plasma level of HIF-1α in patients with NSCLC and healthy volunteers. The results indicated that the 5-year survival rate of patients with squamous cell carcinomas is negatively correlated with the plasma level of HIF-1α and the 5-year survival rate of patients with low level of HIF-1α is higher than those with high level of HIF-1α. The plasma level of HIF-1α in patients with NSCLC is significantly higher than healthy volunteers. There is no significant correlation between the plasma level of HIF-1α and clinical features of NSCLC patients. In a word, there is no connection between the plasma level of HIF-1α and the clinical features of NSCLC patients as well as their prognosis. In stratified analysis, the plasma level of HIF-1α in patients with squamous cell carcinoma is associated with regional lymph node status.
Doubly Resonant Optical Periodic Structure
Authors: Alagappan G. , Png C. E.
Published: February 2016

Periodic structures are well known in various branches of physics for their ability to provide a stopband. In this article, using optical periodic structures we showed that, when a second periodicity – very closed to the original periodicity is introduced, large number of states appears in the stopband corresponding to the first periodicity. In the limit where the two periods matches, we have a continuum of states and the original stopband completely disappears. This intriguing phenomena is uncovered by noticing that, regardless of the proximities of the two periodicities, there is an array of spatial points where the dielectric functions corresponding to the two periodicities interfere destructively. These spatial points mimic photonic atoms by satisfying the standards equations of quantum harmonic oscillators and exhibit lossless, atom-like dispersions.
Joint estimation over multiple individuals improves behavioural state inference from animal movement data
Authors: Jonsen Ian
Published: February 2016

State-space models provide a powerful way to scale up inference of movement behaviours from individuals to populations when the inference is made across multiple individuals. Here, I show how a joint estimation approach that assumes individuals share identical movement parameters can lead to improved inference of behavioural states associated with different movement processes. I use simulated movement paths with known behavioural states to compare estimation error between nonhierarchical and joint estimation formulations of an otherwise identical state-space model. Behavioural state estimation error was strongly affected by the degree of similarity between movement patterns characterising the behavioural states, with less error when movements were strongly dissimilar between states. The joint estimation model improved behavioural state estimation relative to the nonhierarchical model for simulated data with heavy-tailed Argos location errors. When applied to Argos telemetry datasets from 10 Weddell seals, the nonhierarchical model estimated highly uncertain behavioural state switching probabilities for most individuals whereas the joint estimation model yielded substantially less uncertainty. The joint estimation model better resolved the behavioural state sequences across all seals. Hierarchical or joint estimation models should be the preferred choice for estimating behavioural states from animal movement data, especially when location data are error-prone.
Using shared needles for subcutaneous inoculation can transmit bluetongue virus mechanically between ruminant hosts
Authors: Darpel Karin E. , Barber James , Hope Andrew , Wilson Anthony J. , Gubbins Simon , Henstock Mark , Frost Lorraine , Batten Carrie , Veronesi Eva , Moffat Katy , Carpenter Simon , Oura Chris , Mellor Philip S. , Mertens Peter P. C.
Published: February 2016

Bluetongue virus (BTV) is an economically important arbovirus of ruminants that is transmitted byCulicoides spp. biting midges. BTV infection of ruminants results in a high viraemia, suggesting that repeated sharing of needles between animals could result in its iatrogenic transmission. Studies defining the risk of iatrogenic transmission of blood-borne pathogens by less invasive routes, such as subcutaneous or intradermal inoculations are rare, even though the sharing of needles is common practice for these inoculation routes in the veterinary sector. Here we demonstrate that BTV can be transmitted by needle sharing during subcutaneous inoculation, despite the absence of visible blood contamination of the needles. The incubation period, measured from sharing of needles, to detection of BTV in the recipient sheep or cattle, was substantially longer than has previously been reported after experimental infection of ruminants by either direct inoculation of virus, or through blood feeding by infectedCulicoides. Although such mechanical transmission is most likely rare under field condition, these results are likely to influence future advice given in relation to sharing needles during veterinary vaccination campaigns and will also be of interest for the public health sector considering the risk of pathogen transmission during subcutaneous inoculations with re-used needles.
Cross-talk between freezing response and signaling for regulatory transcriptions of MIR475b and its targets by miR475b promoter in Populus suaveolens
Authors: Niu Jun , Wang Jia , Hu Huiwen , Chen Yinlei , An Jiyong , Cai Jian , Sun Runze , Sheng Zhongting , Liu Xieping , Lin Shanzhi
Published: February 2016

MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in post-transcriptional regulation of their target genes, yet the transcriptional regulation of plant miRNAs by promoter is poorly understood. Here, we firstly clone pri-miR475b cDNA and its native promoter from P. suaveolens and characterize Psu-MIR475b as class-II gene transcribed by RNA polymerase II. By 5′ deletion analysis of Psu-miR475b promoter in a series of promoter-GUS chimeric vectors, we functionally identify three positive regulatory regions and multiple cis-acting elements responsible for Psu-miR475b promoter activity in response to freezing stress and exogenous hormone treatment. Moreover, the Psu-miR475b promoter activity displays a tissue-specific manner, negatively regulated by freezing stress and positively by MeJA, SA or GA treatment. Importantly, we comparatively analyze the time-course transcriptional profiles of Psu-miR475b and its targets in Psu-miR475b over-expression transgenic plants controlled by Psu-miR475b-specific promoter or CaMV 35S constitutive promoter and explore the regulatory mechanism of Psu-miR475b promoter controlling transcriptional expressions of Psu-MIR475b and its targets in response to freezing stress and exogenous hormone treatment. Our results reveal that Psu-miR475b promoter-mediated transcriptions of Psu-MIR475b and its targets in response to freezing stress may be involved in a cross-talk between freezing response and stress signaling process.