bluuebunny/crossref_metadata_2025 huggingface dataset:
Hohlraum modeling for opacity experiments on the National Ignition Facility
Authors: Dodd E. S. , DeVolder B. G. , Martin M. E. , Krasheninnikova N. S. , Tregillis I. L. , Perry T. S. , Heeter R. F. , Opachich Y. P. , Moore A. S. , Kline J. L. , Johns H. M. , Liedahl D. A. , Cardenas T. , Olson R. E. , Wilde B. H. , Urbatsch T. J.
Published: June 2018

This paper discusses the modeling of experiments that measure iron opacity in local thermodynamic equilibrium (LTE) using laser-driven hohlraums at the National Ignition Facility (NIF). A previous set of experiments fielded at Sandia's Z facility [Bailey et al., Nature 517, 56 (2015)] have shown up to factors of two discrepancies between the theory and experiment, casting doubt on the validity of the opacity models. The purpose of the new experiments is to make corroborating measurements at the same densities and temperatures, with the initial measurements made at a temperature of 160 eV and an electron density of 0.7 × 1022 cm−3. The X-ray hot spots of a laser-driven hohlraum are not in LTE, and the iron must be shielded from a direct line-of-sight to obtain the data [Perry et al., Phys. Rev. B 54, 5617 (1996)]. This shielding is provided either with the internal structure (e.g., baffles) or external wall shapes that divide the hohlraum into a laser-heated portion and an LTE portion. In contrast, most inertial confinement fusion hohlraums are simple cylinders lacking complex gold walls, and the design codes are not typically applied to targets like those for the opacity experiments. We will discuss the initial basis for the modeling using LASNEX, and the subsequent modeling of five different hohlraum geometries that have been fielded on the NIF to date. This includes a comparison of calculated and measured radiation temperatures.
Order-disorder transition of intrinsically disordered kinase inducible transactivation domain of CREB
Authors: Liu Hao , Guo Xiang , Han Jingcheng , Luo Ray , Chen Hai-Feng
Published: June 2018

Transcription factor cyclic Adenosine monophosphate response-element binding protein plays a critical role in the cyclic AMP response pathway via its intrinsically disordered kinase inducible transactivation domain (KID). KID is one of the most studied intrinsically disordered proteins (IDPs), although most previous studies focus on characterizing its disordered state structures. An interesting question that remains to be answered is how the order-disorder transition occurs at experimental conditions. Thanks to the newly developed IDP-specific force field ff14IDPSFF, the quality of conformer sampling for IDPs has been dramatically improved. In this study, molecular dynamics (MD) simulations were used to study the order-to-disorder transition kinetics of KID based on the good agreement with the experiment on its disordered-state properties. Specifically, we tested four force fields, ff99SBildn, ff99IDPs, ff14IDPSFF, and ff14IDPs in the simulations of KID and found that ff14IDPSFF can generate more diversified disordered conformers and also reproduce more accurate experimental secondary chemical shifts. Kinetics analysis of MD simulations demonstrates that the order-disorder transition of KID obeys the first-order kinetics, and the transition nucleus is I127/L128/L141. The possible transition pathways from the nucleus to the last folded residues were identified as I127-R125-L138-L141-S143-A145 and L128-R125-L138-L141-S143-A145 based on a residue-level dynamical network analysis. These computational studies not only provide testable prediction/hypothesis on the order-disorder transition of KID but also confirm that the ff14IDPSFF force field can be used to explore the correlation between the structure and function of IDPs.
Application of the space-resolving flux detector for radiation measurements from an octahedral-aperture spherical hohlraum
Authors: Xie Xufei , Du Huabing , Chen Jinwen , Liu Shenye , Li Zhichao , Yang Dong , Huang Yunbao , Ren Kuan , Hou Lifei , Li Sanwei , Guo Liang , Jiang Xiaohua , Huo Wenyi , Chen Yaohua , Ren Guoli , Lan Ke , Wang Feng , Jiang Shaoen , Ding Yongkun
Published: June 2018

Space-resolving flux detection is an important technique for the diagnostic of the radiation field within the hohlraum in inertial confinement fusion, especially for the radiation field diagnostic in the novel spherical hohlraum with octahedral six laser entrance holes (LEHs), where localized measurements are necessary for the discrimination of the radiation flux from different LEHs. A novel space-resolving flux detector (SRFD) is developed at the SG-III laser facility for the radiation flux measurement in the first campaign of the octahedral spherical hohlraum energetics experiment. The principle and configuration of the SRFD system is introduced. The radiation flux from the wall of a gas-filled octahedral spherical hohlraum is measured for the first time by placing the SRFD system at the equatorial position of the SG-III laser facility, aiming at the hohlraum wall through one of the six LEHs. The absolute radiation flux from the re-emission area on the hohlraum wall is measured, and good consistency is found between the experimental data and the calculated data from a three-dimensional view factor analysis.
Calibration of micro-capacitance measurement system for thermal barrier coating testing
Authors: Ren Yuan , Chen Dixiang , Wan Chengbiao , Tian Wugang , Pan Mengchun
Published: June 2018

In order to comprehensively evaluate the thermal barrier coating system of an engine blade, an integrated planar sensor combining electromagnetic coils with planar capacitors is designed, in which the capacitance measurement accuracy of the planar capacitor is a key factor. The micro-capacitance measurement system is built based on an impedance analyzer. Because of the influence of non-ideal factors on the measuring system, there is an obvious difference between the measured value and the actual value. It is necessary to calibrate the measured results and eliminate the difference. In this paper, the measurement model of a planar capacitive sensor is established, and the relationship between the measured value and the actual value of capacitance is deduced. The model parameters are estimated with the least square method, and the calibration accuracy is evaluated with experiments under different dielectric conditions. The capacitance measurement error is reduced from 29% ∼ 46.5% to around 1% after calibration, which verifies the feasibility of the calibration method.
Power dissipation in the mixed metal-insulator state of self-heated VO2 single crystals and the effect of sliding domains
Authors: Fisher B. , Patlagan L.
Published: June 2018

The mixed metal-insulator state in VO2 sets on within the current-controlled negative differential resistivity regime of I-V loops traced at ambient temperature. In this state, the stability of I(V) and/or spontaneous switching between initial and final steady states are governed by the load resistance RL in series with the sample. With increasing current (decreasing voltage), the power P = IV reaches a maximum (Pmax) and drops to a minimum (Pmin) along a path that depends on RL. For low enough RL, the ratio Pmax/Pmin may exceed by far the contrast in thermal emissivity from films of VO2 over the metal-insulator transition as reported in Kats et al. [Phys. Rev. X 3, 041004 (2013)]. The minimum is followed by a range of currents where the power increases with current. The return path overlaps the original path and continues towards backward switching. For a few samples, there is evidence from optical microscopy that the portion of the P(I) loop between Pmin and backward switching coincides with the range of currents where semiconducting domains slide within a metallic background. Damage induced in crystals by repeated I-V cycling suppresses domain sliding and flattens P(I) in the respective range of currents. This is consistent with the current dependent excess power dissipation being induced by the sliding domains.
Efficient disintegration strategies with cost constraint in complex networks: The crucial role of nodes near average degree
Authors: Deng Ye , Wu Jun , Xiao Yu , Li Yapeng
Published: June 2018

The study of network disintegration, including controlling disease spread and destroying terrorist organizations, has wide application scenarios and attracts many researchers. In this paper, we concentrate on the network disintegration problem with heterogeneous disintegration cost, where the disintegration cost to eliminate each node might be non-identical. We first put forward a disintegration cost model and an optimization model for disintegration strategy. Then, we analyze the hub strategy, leaf strategy, and the average degree strategy to investigate the nodes tendency of the optimal disintegration strategy. Numerical experiments in three synthetic networks and real-world networks indicate that the disintegration effect of hub strategy drops gradually when the disintegration cost changes from homogeneity to heterogeneity. For the situation of strong heterogeneity of disintegration cost of each node, average degree strategy achieves the maximum disintegration effect gradually. Also, taking another perspective, average degree strategy might enlighten efficient solutions to protect critical infrastructure through strengthening the nodes which are chosen by the average degree strategy.
Dynamics of zonal shear collapse with hydrodynamic electrons
Authors: Hajjar R. J. , Diamond P. H. , Malkov M. A.
Published: June 2018

This paper presents a theory for the collapse of the edge zonal shear layer, as observed at the density limit at low β. This paper investigates the scaling of the transport and mean profiles with the adiabaticity parameter α, with special emphasizes on fluxes relevant to zonal flow (ZF) generation. We show that the adiabaticity parameter characterizes the strength of production of zonal flows and so determines the state of turbulence. A 1D reduced model that self-consistently describes the spatiotemporal evolution of the mean density n¯, the azimuthal flow v¯y, and the turbulent potential enstrophy ε=⟨(ñ−∇2ϕ̃)2/2⟩—related to fluctuation intensity—is presented. Quasi-linear analysis determines how the particle flux Γn and vorticity flux Π=−χy∇2vy+Πres scale with α, in both hydrodynamic and adiabatic regimes. As the plasma response passes from adiabatic (α > 1) to hydrodynamic (α < 1), the particle flux Γn is enhanced and the turbulent viscosity χy increases. However, the residual flux Πres—which drives the flow—drops with α. As a result, the mean vorticity gradient ∇2v¯y=Πres/χy—representative of the strength of the shear—also drops. The shear layer then collapses and turbulence is enhanced. The collapse is due to a decrease in ZF production, not an increase in damping. A physical picture for the onset of collapse is presented. The findings of this paper are used to motivate an explanation of the phenomenology of low β density limit evolution. A change from adiabatic (α=kz2vth2/(|ω|νei)>1) to hydrodynamic (α < 1) electron dynamics is associated with the density limit.
Ion density evolution in a high-power sputtering discharge with bipolar pulsing
Authors: Britun N. , Michiels M. , Godfroid T. , Snyders R.
Published: June 2018

Time evolution of sputtered metal ions in high power impulse magnetron sputtering (HiPIMS) discharge with a positive voltage pulse applied after a negative one (regime called “bipolar pulse HiPIMS”—BPH) is studied using 2-D density mapping. It is demonstrated that the ion propagation dynamics is mainly affected by the amplitude and duration of the positive pulse. Such effects as ion repulsion from the cathode and the ionization zone shrinkage due to electron drift towards the cathode are clearly observed during the positive pulse. The BPH mode also alters the film crystallographic structure, as observed from X-ray diffraction analysis.
Improving computational accuracy in dissipative particle dynamics via a high order symplectic method
Authors: Yamada Toru , Itoh Shugo , Morinishi Yohei , Tamano Shinji
Published: June 2018

This study was focused on improving the numerical accuracy of the dissipative particle dynamics simulation via modifying its numerical time integration scheme. Despite the integration of the pairwise Langevin part dealt with by most of the previous studies, we paid attention to the improvement of the standard Liouville part. The numerical accuracy was measured by the configurational temperature in this study. Employing a fourth order symplectic scheme showed a significant improvement of the numerical accuracy for the simulations especially with a large time increment when comparing it with existing schemes, which indicates that enough resolution in time was attained when our modified scheme was employed. In addition, a set of simulations was performed for a wider range of time increments than previous studies. The results showed that the computational error demonstrated different orders of accuracy for different time increment ranges, which led to the fact that the dominant effect on the error is conservative and random forces for the large and small increment ranges.
Effect of curvature in the magnetic shear profile on micro-tearing modes in the tokamak pedestal
Authors: Mahajan S. M. , Hazeltine R. D.
Published: June 2018

The pedestal region of a tokamak plasma differs from the core in several respects. This work emphasizes the magnetic shear profile in the pedestal which is distinctive for two reasons: the pedestal is close to a magnetic-field separatrix so that the q-profile is intrinsically steep, and the steep pedestal gradients cause a peak in the bootstrap current with obvious effects on q(r). In fact, the pedestal q-profile has a complicated structure yielding a curved magnetic shear profile. Global linear simulations suggest that such a q-profile could substantially affect the nature of micro-instabilities. This paper analytically investigates this special feature of the pedestal, after appropriately modifying the slab-model field equations to allow for more complicated variation of the parallel wave vector. Surprisingly, the departure from a locally linear q profile (flat magnetic shear), even when small, supports a qualitatively novel mode whose width is fixed by curvature in the profile. The mode is unstable; its substantial growth rate is robust in the sense of persisting even when the q-profile modification is assumed to be small. However, this mode, originating from details of the q-profile, will not be found in a typical local ballooning gyrokinetic simulation.
Feeding flocks on rangelands: insights into the local ecological knowledge of shepherds in Boulemane province (Morocco)
Authors: Gobindram N.-E. , Boughalmi A. , Moulin C. H. , Meuret M. , Bastianelli D. , Araba A. , Jouven M.
Published: June 2018

In Mediterranean regions, traditional pastoral systems involve shepherds leading flocks along daily grazing circuits on arid rangelands. Over the past decades, these systems have become increasingly agro-pastoral and the importance given to feeding flocks on rangelands is variable. Our study aimed at investigating the local ecological knowledge (LEK) about forage plants and animal foraging behaviour of shepherds in a pastoral area of Morocco, and eventually analysing the possible interactions between such LEK, its utilisation for grazing management and the pastoral status of the farm. Eleven semi-directive interviews with shepherds, either salaried or owning their own farm, were carried out at three sites differing in terms of agricultural context and available forage resources. Shepherds’ LEK included recognising and naming forage plants and rangeland types, identifying preferred or less preferred plants or plant parts, describing circumstantial palatability of plants depending mainly on season, other locally available plants and watering times. LEK about animal feeding preferences and its integration into grazing management was more extensive at sites where pastoral systems were still most valued, and for shepherds who were either experienced or who were considering the activity in the future. Conversely, young salaried shepherds or farmer-shepherds who devoted more attention to the agricultural component of their system seemed to be less knowledgeable about the subject. In a context where pastoralism is challenged both by the higher profitability of agriculture and by the depletion of pastoral resources as a result of frequent droughts and decreased surface area devoted to grazing lands, the future of such LEK is uncertain. The perpetuation of LEK might depend on the ability of local extension services to value farmers’ LEK and to help them enrich it with scientific knowledge.
Upset-resistance welding of aluminium to copper rods: Effect of interface on performance
Authors: Shamsian M. , Movahedi M. , Kokabi A. H. , Ozlati A.
Published: June 2018

Upset resistance dissimilar welding of aluminium and copper narrow rods was performed. Effect of the interface characteristics was studied on the joint mechanical and electrical properties. Upset resistance welding (URW) was successful for production of joints with high strength and electrical conductivity between aluminium and copper rods. Reaction layer at the joint interface was composed of the Al2Cu cellular phase and lamellar eutectic structure of α-Al and Al2Cu. Enhancement of the welding current and decrease in the upset force increased the reaction layer thickness and strength of the joint. URW had no significant detrimental effect on the electrical conductivity of the weld zone. Neither the joint strength nor the joint electrical conductivity was improved by in situ post weld heat treatment.
Application of the filter plate microbial trap (FPMT), for cultivating thermophilic bacteria from thermal springs in Barguzin area, eastern Baikal, Russia
Authors: Jung Dawoon , Seo Eun-Young , Owen Jeffrey S , Aoi Yoshiteru , Yong Seungcheon , Lavrentyeva Elena V , Ahn Tae Seok
Published: June 2018

Hot springs are regarded as treasury of valuable thermophiles. Like other bacteria, thermophiles are not easily cultivated using conventional culture methods. We used an advanced cultivation method, the filter plate microbial trap (FPMT), to isolate bacteria from thermal springs. In total, 184 isolates were obtained from five thermal springs using the FPMT and standard agar plate method, and their 16S rRNA gene sequences were analyzed. FPMT allowed us to obtain a culture collection that was larger, richer, and more novel than that obtained by standard cultivation. Seven novel species were obtained using the FPMT technique, whereas only one was isolated using a standard cultivation. We also found clear differences in the patterns of phylogenetic diversity and physiological properties between isolates from two cultivation methods. The results have encouraged us to apply the FPMT method in other extreme environments and offer further support for fostering the development of new cultivation methods.
The Lilien Partbooks in the Sonsfeld Collection (D-HRD Fü 3741a): A Reconsideration of the Role of Eighteenth-Century Prussian Hautboisten and their Engagement in ‘Art’ Music
Authors: Corall Georg
Published: June 2018

In assuming that the violin family of instruments is the staple of Western instrumental art music, Hautboisten, among the most important musicians of the seventeenth and eighteenth centuries, constitute a neglected area of research. Hautboisten are known to have been among the major suppliers of musical entertainment in the German-speaking lands in the first half of the eighteenth century. The term Hautboistenbande has often been translated by contemporary scholars as ‘oboe band’. Indeed, these ensembles developed into wind bands known as Harmoniemusik; Hautboisten, however, were originally routinely trained to perform on multiple wind instruments as well as string instruments.

The Lilien Partbooks, which are part of the Sonsfeld Collection (the Sonsfeldsche Musikalien Sammlung; now held in the Bibliotheca Fürstenbergiana in Herdringen; D-HRD Fü 3741a), represent the most comprehensive primary source of music for such an ensemble. A detailed incipit catalogue of the compositions compiled in these partbooks draws together our current knowledge of the Lilien Partbooks and of eighteenth-century Prussian Hautboisten. The extensive catalogue of the works collated in the six partbooks constitutes a valuable aid for future research.
Strong approximation over function fields
Authors: Chen Qile , Zhu Yi
Published: June 2018

By studying

A

1

\mathbb {A}^1

-curves on varieties, we propose a geometric approach to the strong approximation problem over function fields of complex curves. We prove that strong approximation holds for smooth, low degree affine complete intersections with smooth boundary at infinity.
A structural equation model of the family physicians attitude towards their role in prevention: a cross-sectional study in Switzerland
Authors: Cohidon Christine , Wild Pascal , Senn Nicolas
Published: June 2018

Background

In contrast to many studies exploring barriers to preventive care in family medicine, there is less quantitative research regarding the self-perceived role of family physicians (FPs) in prevention and its predictive factors. Moreover, the existing studies considered this attitude as a homogeneous entity. The objective of this study is firstly, to characterize FPs’ attitudes towards prevention taking into account nine different prevention themes, and secondly, to explore the factors that could be predictive of this attitude.

Methods

The data stem from a cross-sectional national survey on prevention we conducted in Switzerland from 2015 to 2016 (170 physicians randomly drawn, online questionnaire). We first performed a confirmatory factor analysis to define a homogeneous latent variable regarding physicians’ attitude towards prevention, then, a structural equation modeling to identify potential predictors.

Results

The FP’ attitude towards their role in preventive care was homogeneously positive whatever the topic (smoking, drinking dietary habits, physical activities, and more generally, cardiovascular risk factors) except for occupational risks and cannabis consumption. A feeling of good effectiveness was a positive predictor of this positive attitude while seniority, the lack of reimbursement and being a physician from the German-speaking area were negative predictors.

Conclusion

The FP’ attitude about their role in prevention is homogeneous concerning the ‘classical’ topics of prevention, whereas they still under-recognize certain topics as important fields for prevention. To change this situation, we probably need a global effort to introduce other ways of thinking about prevention, including not only FP but also all stakeholders.
Beyond Victimhood and Beyond Employment? Exploring Avenues for Labour Law to Empower Women Trafficked into the Sex Industry
Authors: Thiemann Inga K
Published: June 2018

This article explores under which circumstances a labour law approach could make a meaningful contribution to combatting human trafficking into the sex industry. In this, I critique the existing criminal law approach to human trafficking and its policies, which focus on trafficked persons as idealised victims in need of protection, rather than on their rights as workers, migrants and women. Furthermore, I also challenge the exclusion of sex workers from arguments for a labour law response to human trafficking, as they maintain the construction of trafficking for sexual exploitation and trafficking for labour exploitation as separate phenomena. Instead, this article advocates an alternative labour law approach to human trafficking, which incorporates wider interdisciplinary issues of gender equality and societal exclusions for women and migrants, and particularly female migrant sex workers, within a labour response. My focus is therefore on exclusions maintained by existing labour legislation, which are based on the standard employment contract and amplified by barriers to labour protections faced by workers in female-dominated service jobs in general and by sex workers in particular. As sex workers’ embodied feminised labour is deemed not to be ‘real work’, they seem to be unworthy of labour protections. My proposed labour response to human trafficking into the sex industry therefore combines some of the strengths of the existing labour rights-focussed anti-trafficking and exploitation discourse with arguments from feminist labour law theory in order to tackle the intersectional dimension of human trafficking into the sex industry.
Association of the rs495392 Klotho polymorphism with atheromatosis progression in patients with chronic kidney disease
Authors: Valdivielso José M , Bozic Milica , Galimudi Rajesh Kumar , Bermudez-López Marcelino , Navarro-González Juan F , Fernández Elvira , Betriu Àngels
Published: June 2018

Background

Prevalence of atherosclerotic cardiovascular disease and its rate of progression are higher in patients with chronic kidney disease (CKD) compared with the general population. Mineral metabolism parameters have been shown to be involved in the increased velocity of atheromatosis progression. The aim of this study is to determine the role of 11 single-nucleotide polymorphisms (SNPs) of the Klotho gene on the rate of atherosclerosis progression in CKD.

Methods

This was a multicentre, prospective, observational study of 1439 CKD patients from the NEFRONA cohort. Carotid and femoral ultrasounds were performed at baseline and after 24 months in 10 arterial territories. Progression of atheromatosis was defined as an increase in the number of territories with plaque. Genotyping of 11 SNPs of the Klotho gene was performed and its association with atheromatosis progression was determined by multivariate logistic regression.

Results

Bivariate analysis showed that none of the 11 SNPs was associated with atheroma plaque prevalence, but 3 of them (rs495392, rs562020 and rs567170) showed association with atheromatosis progression. The multivariate analysis revealed that only rs495392 showed a statistically significant association with atheromatosis progression, after adjustment for several parameters known to affect it in CKD patients. Thus, the presence of one allele T was associated with a reduction of 30% of the odds of progression, whereas the presence of the two T alleles was associated with a decrease close to 50%.

Conclusions

The presence of the allele T of the SNP rs495392 of the Klotho gene is associated with a decrease in the odds of progression of atheromatosis in CKD patients.
Can the Ceftriaxone Breakpoints Be Increased Without Compromising Patient Outcomes?
Authors: Tamma Pranita D , Pierce Virginia M , Cosgrove Sara E , Lautenbach Ebbing , Harris Anthony , Rayapati Divya , Han Jennifer H
Published: June 2018

Background

In 2010, the Clinical Laboratory and Standards Institute recommended a 3-fold lowering of ceftriaxone breakpoints to 1 mcg/mL for Enterobacteriaceae. Supportive clinical data at the time were from fewer than 50 patients. We compared the clinical outcomes of adults with Enterobacteriaceae bloodstream infections treated with ceftriaxone compared with matched patients (with exact matching on ceftriaxone minimum inhibitory concentrations [MICs]) treated with extended-spectrum agents to determine if ceftriaxone breakpoints could be increased without negatively impacting patient outcomes.

Methods

A retrospective cohort study was conducted at 3 large academic medical centers and included patients with Enterobacteriaceae bacteremia with ceftriaxone MICs of 2 mcg/mL treated with ceftriaxone or extended-spectrum β-lactams (ie, cefepime, piperacillin/tazobactam, meropenem, or imipenem/cilastatin) between 2008 and 2014; 1:2 nearest neighbor propensity score matching was performed to estimate the odds of recurrent bacteremia and mortality within 30 days.

Results

Propensity score matching yielded 108 patients in the ceftriaxone group and 216 patients in the extended-spectrum β-lactam group, with both groups well-balanced on demographics, preexisting medical conditions, severity of illness, source of bacteremia, and source control interventions. No difference in recurrent bacteremia (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.49–2.73) or mortality (OR, 1.27; 95% CI, 0.56–2.91) between the treatment groups was observed for patients with isolates with ceftriaxone MICs of 2 mcg/mL. Only 6 isolates (1.6%) with ceftriaxone MICs of 2 mcg/mL were extended-spectrum β-lactamase (ESBL)–producing.

Conclusions

Our findings suggest that patient outcomes are similar when receiving ceftriaxone vs extended-spectrum agents for the treatment of Enterobacteriaceae bloodstream infections with ceftriaxone MICs of 2 mcg/mL. This warrants consideration of adjusting the ceftriaxone susceptibility breakpoint from 1 to 2 mcg/mL, as a relatively small increase in the antibiotic breakpoint could have the potential to limit the use of large numbers of extended-spectrum antibiotic agents.
Antiviral treatment for outpatient use during an influenza pandemic: a decision tree model of outcomes averted and cost-effectiveness
Authors: Venkatesan Sudhir , Carias Cristina , Biggerstaff Matthew , Campbell Angela P , Nguyen-Van-Tam Jonathan S , Kahn Emily , Myles Puja R , Meltzer Martin I
Published: June 2018

Background

Many countries have acquired antiviral stockpiles for pandemic influenza mitigation and a significant part of the stockpile may be focussed towards community-based treatment.

Methods

We developed a spreadsheet-based, decision tree model to assess outcomes averted and cost-effectiveness of antiviral treatment for outpatient use from the perspective of the healthcare payer in the UK. We defined five pandemic scenarios—one based on the 2009 A(H1N1) pandemic and four hypothetical scenarios varying in measures of transmissibility and severity.

Results

Community-based antiviral treatment was estimated to avert 14–23% of hospitalizations in an overall population of 62.28 million. Higher proportions of averted outcomes were seen in patients with high-risk conditions, when compared to non-high-risk patients. We found that antiviral treatment was cost-saving across pandemic scenarios for high-risk population groups, and cost-saving for the overall population in higher severity influenza pandemics. Antiviral effectiveness had the greatest influence on both the number of hospitalizations averted and on cost-effectiveness.

Conclusions

This analysis shows that across pandemic scenarios, antiviral treatment can be cost-saving for population groups at high risk of influenza-related complications.
Targeting toll-like receptor-4 (TLR4)—an emerging therapeutic target for persistent pain states
Authors: Bruno Kelly , Woller Sarah A. , Miller Yury I. , Yaksh Tony L. , Wallace Mark , Beaton Graham , Chakravarthy Krishnan
Published: June 2018

Toll-like receptors (TLRs) are a family of pattern recognition receptors that initiate signaling in innate and adaptive immune pathways. The highly conserved family of transmembrane proteins comprises an extracellular domain that recognizes exogenous and endogenous danger molecules and an ectodomain that activates downstream pathways in response. Recent studies suggest that continuous activation or dysregulation of TLR signaling may contribute to chronic disease states. The receptor is located not only on inflammatory cells (meningeal and peripheral macrophages) but on neuraxial glia (microglia and astrocytes), Schwann cells, fibroblasts, dorsal root ganglia, and dorsal horn neurons. Procedures blocking TLR functionality have shown pronounced effects on pain behavior otherwise observed in models of chronic inflammation and nerve injury. This review addresses the role of TLR4 as an emerging therapeutic target for the evolution of persistent pain and its role in noncanonical signaling, mediating anomalous pro-algesic actions of opiates. Accordingly, molecules targeting inhibition of this receptor have promise as disease-modifying and opioid-sparing alternatives for persistent pain states.
Engaging Smokeless Tobacco Users in Population-Based Cessation Services: Findings From an Observational Study
Authors: Keller Paula A. , Boyle Raymond G. , Lien Rebecca K. , Christiansen Bruce , Kobinsky Kate
Published: June 2018

Although telephone quitlines are effective for helping smokeless tobacco (ST) users quit, ST users are underrepresented among quitline participants. After ClearWay MinnesotaSM implemented multiple changes to its quitline service (QUITPLAN® Services), utilization increased dramatically, including by ST users. We examined data from Minnesota and Wisconsin to determine whether these changes were unique to Minnesota. Four years of quitline registration data were analyzed for both states. A significant increase in enrollees reporting any ST use was seen in Minnesota after changes were made to services; no change was seen in Wisconsin. A 2-week starter kit of nicotine replacement therapy and the ability to register for services online were popular among Minnesotans reporting ST use. This study suggests that quitline services can be designed to increase participation by ST users.
Varicella Vaccination Among US Adolescents: Coverage and Missed Opportunities, 2007-2014
Authors: Leung Jessica , Reagan-Steiner Sarah , Lopez Adriana , Jeyarajah Jenny , Marin Mona
Published: June 2018

Context:

Since 2007, 2 doses of varicella vaccine have been routinely recommended, with a catch-up second dose recommended for those who received only 1 prior dose.

Objective:

To examine varicella vaccination coverage with 2 or more doses and the proportions of adolescents with evidence of immunity to varicella (≥2 doses of vaccine or varicella history) during 2007-2014. To assess timing of second-dose receipt, factors associated with 2 or more vaccine doses, and missed second-dose opportunities during 2014.

Design, Setting, and Participants:

We used data from the 2007-2014 National Immunization Survey–Teen (NIS-Teen), which collects information on adolescents aged 13 to 17 years in the United States.

Results:

From 2007 to 2014, varicella vaccination coverage with 2 or more doses increased from 8.3% to 66.9% in 13- to 15-year-olds and from 3.6% to 56.7% in 16- to 17-year-olds. The proportions with evidence of immunity also increased from 68.0% to 84.1% (13- to 15-year-olds) and 78.6% to 83.4% (16- to 17-year-olds). In 2014, 13.4% of 13- to 15-year-olds and 3.2% of 16- to 17-year-olds had received their second dose at 4 to 6 years of age. Factors most significantly associated with lower coverage with 2 or more doses were not having an 11- to 12-year well-child visit, not receiving an adolescent vaccine, and residence in a state with no 2-dose immunization school entry requirement. Seventy-seven percent of 1-dose vaccinated adolescents had 1 or more missed opportunities to receive their second dose; if were they not missed, 2-dose coverage would have increased from 79.5% to 94.8%.

Conclusions:

Levels of varicella vaccination coverage with 2 or more doses and the proportion of adolescents with evidence of immunity increased from 2007 to 2014, though 16% lacked evidence of immunity in 2014. Although catch-up campaigns have succeeded, missed vaccination opportunities persist.
Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation
Authors: Adorno Maddalena , di Robilant Benedetta Nicolis , Sikandar Shaheen , Acosta Veronica Haro , Antony Jane , Heller Craig , Clarke Michael F.
Published: June 2018

Regulation of the Wnt pathway in stem cells and primary tissues is still poorly understood. Here we report that Usp16, a negative regulator of Bmi1/PRC1 function, modulates the Wnt pathway in mammary epithelia, primary human fibroblasts and MEFs, affecting their expansion and self-renewal potential. In mammary glands, reduced levels of Usp16 increase tissue responsiveness to Wnt, resulting in upregulation of the downstream Wnt target Axin2, expansion of the basal compartment and increased in vitro and in vivo epithelial regeneration. Usp16 regulation of the Wnt pathway in mouse and human tissues is at least in part mediated by activation of Cdkn2a, a regulator of senescence. At the molecular level, Usp16 affects Rspo-mediated phosphorylation of LRP6. In Down’s Syndrome (DS), triplication of Usp16 dampens the activation of the Wnt pathway. Usp16 copy number normalization restores normal Wnt activation in Ts65Dn mice models. Genetic upregulation of the Wnt pathway in Ts65Dn mice rescues the proliferation defect observed in mammary epithelial cells. All together, these findings link important stem cell regulators like Bmi1/Usp16 and Cdkn2a to Wnt signaling, and have implications for designing therapies for conditions, like DS, aging or degenerative diseases, where the Wnt pathway is hampered.
Fast Non-Parametric Estimation of Outbreak Growth from Cumulative Incidence Applied to the Current Ebola Epidemic
Authors: House Thomas
Published: June 2018

A method is presented that works with cumulative incidence data to provide a real-time estimate of the growth rate of an outbreak, without assuming any particular disease dynamics, and this is applied to the current Ebola outbreak.
A promoter interaction map for cardiovascular disease genetics
Authors: Montefiori Lindsey E. , Sobreira Débora R. , Sakabe Noboru J. , Aneas Ivy , Joslin Amelia C. , Hansen Grace T. , Bozek Grazyna , Moskowitz Ivan P. , McNally Elizabeth M. , Nóbrega Marcelo A.
Published: June 2018

Over 500 genetic loci have been associated with risk of cardiovascular diseases (CVDs), however most loci are located in gene-distal non-coding regions and their target genes are not known. Here, we generated high-resolution promoter capture Hi-C (PCHi-C) maps in human induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes (CMs) to provide a resource for identifying and prioritizing the functional targets of CVD associations. We validate these maps by demonstrating that promoters preferentially contact distal sequences enriched for tissue-specific transcription factor motifs and are enriched for chromatin marks that correlate with dynamic changes in gene expression. Using the CM PCHi-C map, we linked 1,999 CVD-associated SNPs to 347 target genes. Remarkably, more than 90% of SNP-target gene interactions did not involve the nearest gene, while 40% of SNPs interacted with at least two genes, demonstrating the importance of considering long-range chromatin interactions when interpreting functional targets of disease loci.
The role of homology and orthology in the phylogenomic analysis of metazoan gene content
Authors: Pett Walker , Adamski Marcin , Adamska Maja , Francis Warren R. , Eitel Michael , Pisani Davide , Wörheide Gert
Published: June 2018

Resolving animal (Metazoa) relationships is crucial to our understanding of, for example, the origin of their key traits such as muscles, guts and nerves. However, a broadly accepted metazoan consensus phylogeny has yet to emerge. In part this is because the genomes of deeply-diverging and fast-evolving lineages may undergo significant gene turnover, reducing the number of orthologs shared with related phyla. This can limit the usefulness of traditional phylogenetic methods that rely on alignments of orthologous sequences. Phylogenetic analysis of gene content has the potential to circumvent this orthology requirement, with binary presence/absence of homologous gene families representing a source of phylogenetically informative characters. Applying binary substitution models to the gene content of 26 complete animal genomes, we demonstrate that patterns of gene conservation differ markedly depending on whether gene families are defined by orthology or homology, i.e., whether paralogs are excluded or included. We conclude that the placement of deeply-diverging lineages, like ctenophores, may exceed the limit of resolution afforded by methods based on comparisons of orthologous protein supermatrices, and novel approaches are required to fully capture the evolutionary signal from genes within genomes.
Cryptic Dispersal Networks Connect Habitat Patches in ways not Captured by Distance
Authors: Germain Rachel M. , Jones Natalie T. , Grainger Tess N.
Published: June 2018

Species interact with the physical world in complex ways, and life history strategies might cause species to differ in how they experience connectedness of the same landscape. As a consequence, dispersal limitation might be present but not captured by distance-based measures of connectivity. To test these ideas, we surveyed plant communities that associate with serpentine soils but differ in dispersal mode (gravity, animal, or wind), and used satellite imagery to quantify forms of landscape connectivity associated with each dispersal mode. Our data yielded two key insights: First, dispersal limitation appeared to be absent using a conventional distance-based measure of connectivity, but emerged after considering forms of landscape connectivity relevant to each dispersal mode. Second, the landscape variables that emerged as important to each dispersal mode were generally consistent with our predictions based on putative dispersal vectors, and included interactive effects that allude to the altered efficacy of animal dispersal in invaded landscapes. Our results have broad implications for understanding how ecological communities reorganize as landscapes are fragmented, patches are lost, and the function of dispersal life histories is altered.
Distinct CED-10/Rac1 Domains Confer Context-Specific Functions in Neuronal Development
Authors: Nørgaard Steffen , Deng Shuer , Cao Wei , Pocock Roger
Published: June 2018

Rac GTPases act as master switches to coordinate multiple interweaved signaling pathways. A major function for Rac GTPases is to control neurite development by influencing downstream effector molecules and pathways. InCaenorhabditis elegans, the Rac proteins CED-10, RAC-2 and MIG-2 act in parallel to control axon outgrowth and guidance. Here, we have identified a single glycine residue in the CED-10/Rac1 Switch 1 region that confers a non-redundant function in axon outgrowth but not guidance. Mutation of this glycine to glutamic acid (G30E) reduces GTP binding and inhibits axon outgrowth but does not affect other canonical CED-10 functions. This demonstrates previously unappreciated domain-specific functions within the CED-10 protein. Further, we reveal that when CED-10 function is diminished, the adaptor protein NAB-1 (Neurabin) and its interacting partner SYD-1 (Rho-GAP-like protein) can act as inhibitors of axon outgrowth. Together, we reveal that specific domains and residues within Rac GTPases can confer context-dependent functions during animal development.
Arabidopsis species deploy distinct strategies to cope with drought stress
Authors: Bouzid M. , He F. , Schmitz G. , Häusler R.E. , Weber A.P.M. , Mettler-Altmann T. , de Meaux J.
Published: June 2018

Background and Aims Water limitation is an important determinant of the distribution, abundance and diversity of plant species. Yet, little is known about how the response to limiting water supply changes among closely related plant species with distinct ecological preferences. Comparison of the model annual species A. thaliana to its close perennial relatives A. lyrata and A. halleri, can help disentangle the molecular and physiological changes contributing to tolerance and avoidance mechanisms, because these species must maintain tolerance and avoidance mechanisms to increase long-term survival, but they are exposed to different levels of water stress and competition in their natural habitat.

Methods We conducted a dry-down experiment that mimics a period of missing precipitation. We quantified the covariation of progressive decrease in soil water content (SWC) with various physiological and morphological plant traits across a set of representative genotypes in Arabidopsis thaliana, A. lyrata and A. halleri. To quantify the degree of plant stress, transcriptome changes were also monitored.

Key Results The analysis of trait co-variation demonstrates that the three species differ in the strategies they deploy to respond to drought stress. A. thaliana showed drought avoidance reaction but failed to survive wilting. A. lyrata efficiently combined avoidance and tolerance mechanisms. By contrast, A. halleri showed some degree of tolerance to wilting but it did not seem to protect itself from the stress imposed by drought. Transcriptome data collected just before plant wilting and after recovery corroborated the phenotypic analysis, with A. lyrata and A. halleri showing a stronger activation of recovery- and stress-related genes, respectively.

Conclusions We conclude that these three Arabidopsis species have evolved distinct strategies to face drought stress, and discuss the extent to which these strategic differences reflect their respective ecological priorities.
Genetic Diversity Study of Fusarium culmorum: Causal agent of wheat crown rot in Iraq
Authors: Matny O. N. , Shamsallah S. A. , Haas M.
Published: June 2018

Fusarium crown rot (FCR), caused by Fusarium culmorum (Wm.G.Sm) Sacc., is an important disease of wheat both in Iraq and other regions of wheat production worldwide. Changes in environmental conditions and cultural practices such as crop rotation generate stress on pathogen populations leading to the evolution of new strains that can tolerate more stressful environments. This study aims to investigate the genetic diversity among isolates of F. culmorum in Iraq. Twenty-nine samples were collected from different regions of wheat cultivation in Iraq to investigate the pathogenicity and genetic diversity of F. culmorum using the REP-PCR technique. Among the twenty-nine isolates of F. culmorum examined for pathogenicity, 96% were pathogenic to wheat at the seedling stage. The most aggressive isolate, from Baghdad, was IF 0021 at 0.890 on the FCR severity index. Three primer sets were used to assess the genotypic diversity via REP, ERIC and BOX elements. The amplicon sizes ranged from 200-800 bp for BOX-ERIC2, 110-1100 bp for ERIC-ERIC2 and 200-1300 bp for REP. In total, 410 markers were polymorphic, including 106 for BOX, 175 for ERIC and 129 for the REP. Genetic similarity was calculated by comparing markers according to minimum variance (Squared Euclidean). Clustering analysis generated two major groups, group 1 with two subgroup 1a and 1b with 5 and 12 isolates respectively, and group 2 with two subgroups 2a and 2b with 3 and 9 isolates respectively. This is the first study in this field that has been reported in Iraq.
Thresholding of sensory inputs by extrasynaptic glutamate receptors in olfactory bulb glomeruli
Authors: Gire D.H. , Zak J.D. , Bourne J.N. , Goodson N.B. , Lynch B.E. , Dulla C.G. , Schoppa N.E.
Published: June 2018

The mammalian olfactory bulb has presented a challenging system for understanding information processing, in part because the bulb largely lacks the topographical ordering of neurons that promotes processes such as lateral inhibition. Here we have used dual and triple-cell recordings in rodent bulb slices combined with ultrastructural methods to provide the first experimental evidence for a processing mechanism circumventing this problem that operates at the level of single glomeruli, the bulb’s odorant receptor-specific modules. A key feature is non-traditional, extrasynaptic glutamatergic signaling derived from excitatory interneurons and what it means for the local balance between excitation (E) and inhibition (I). We found that the distinct dynamic properties of extrasynaptic excitation versus synaptic inhibition create a thresholding effect whereby only strong stimuli produce a favorable E/I balance enabling an output. This single-glomerulus threshold could have a number of important functions during natural odor responses, for example enhancing stimulus tuning.