bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of donor cells’ sex on nuclear transfer efficiency and telomere lengths of cloned goats
Authors: Liu H‐j , Peng H , Hu C‐c , Li X‐y , Zhang J‐l , Zheng Z , Zhang W‐c
Published: August 2016

Contents

The aim of this study was to investigate the effects of donor cells’ sex on nuclear transfer efficiency and telomere length of cloned goats from adult skin fibroblast cells. The telomere length of somatic cell cloned goats and their offspring was determined by measuring their mean terminal restriction fragment (TRF) length. The result showed that (i) reconstructed embryos with fibroblast cells from males Boer goats obtained significantly higher kids rate and rate of live kids than those of female embryos and (ii) the telomere lengths of four female cloned goats were shorter compared to their donor cells, but five male cloned goats had the same telomere length with their donor cells, mainly due to great variation existed among them. The offspring from female cloned goats had the same telomere length with their age‐matched counterparts. In conclusion, the donor cells’ sex had significant effects on nuclear transfer efficiency and telomere lengths of cloned goats.
Celebrities and the stage: theatrical stardom in early modern Spain
Authors: García‐Reidy Alejandro
Published: August 2016

This article seeks to apply a number of concepts and approaches developed by celebrity studies during the past decades in the field of early modern theatre. More specifically, I will focus on the commercial theatre that developed in Spain from the 1560s onwards. This dramatic practice represents a privileged vantage point from which to observe how a number of key dynamics related to celebrity culture came into play within the context of early modern society, as the characteristics of this business and its cultural impact allowed for the emergence of processes of celebrification among performers. This study focuses on the characteristics of this theatre that made it possible for an early modern version of celebrity to emerge, such as the large role that actresses played in its success or the contact with performers that a wide variety of audiences enjoyed all along the country. I also analyse how actors and actresses were subject to forces of commodification, eroticization and the public's attention to their private lives, which led them to become early modern stars.
A comparison of coping strategies in patients with fibromyalgia, chronic neuropathic pain, and pain‐free controls
Authors: Baastrup Sidsel , Schultz Rikke , Brødsgaard Inger , Moore Rod , Jensen Troels S. , Vase Toft Lene , Bach Flemming W. , Rosenberg Raben , Gormsen Lise
Published: August 2016

Patients suffering from chronic pain may benefit from learning adaptive coping strategies. Consensus on efficient strategies for this group of patients is, however, lacking, and previous studies have shown inconsistent results. The present study has examined coping strategies in two distinctly different groups of chronic pain patients and a group of healthy controls. Thirty neuropathic pain (NP) patients, 28 fibromyalgia (FM) patients, and 26 pain‐free healthy controls completed the Coping Strategy Questionnaire (CSQ‐48/27) and rated their daily pain. The results showed that FM and NP patients did not cope differently with pain. The only difference between the groups was that FM patients felt more in control of their pain than NP patients. Both patient groups used more maladaptive/passive coping strategies, but surprisingly also more adaptive/active coping strategies than healthy controls. However, FM patients with high levels of passive strategies felt less in control than FM patients with low levels of passive strategies. This was not seen in NP patients. An important implication for clinical practice is therefore that passive coping strategies should be restructured into active ones, especially for FM patients. Otherwise, the same psychological treatment model can be applied to both groups since they use similar coping styles.
How to characterize ‘good’ and ‘greening’ in the EU Common Agricultural Policy (CAP): the case of clay soils in the Netherlands
Authors: Bouma J. , Wösten J. H. M.
Published: August 2016

The change in the Common Agricultural Policy (CAP) of the European Union from product to producer support, including requirements for ‘good agricultural and environmental conditions’ and ‘greening’, is excellent. However, these requirements are now defined in rather general terms. Questions can be raised about suitable indicators, and there is a recognized need for effective management recommendations to support farmers in achieving the required ‘good’ conditions. These recommendations are bound to be quite different for different soils in different countries. A study of Dutch clay soils was based on a storyline describing current problems and management options for improvement, which were quantified using a soil–water–crop simulation model. Indicators were defined for agricultural conditions and suggestions made for the use of the model in a predictive mode to help farmers improve their soil management. Environmental conditions were judged by current environmental guidelines for water and air. When modelling, implicit assumptions that soils are homogeneous were shown to be unrealistic for these clay soils, requiring development of innovative methods and procedures, presenting a challenge for soil research.
Lime placement on subsoil as a strategy to reduce phosphorus leaching from agricultural soils
Authors: Andersson H. , Bergström L. , Djodjic F. , Ulén B. , Kirchmann H.
Published: August 2016

Leaching of phosphorus (P) from agricultural land is a major contributor to eutrophication of surface waters in many countries, and effective mitigation options to reduce P in leachate are needed. In this study, intact columns (0.77 m deep) of subsoil from three Swedish agricultural soils (one sand and two clay) were used to examine whether placing quicklime (calcium oxide, CaO) on the subsoil could reduce P leaching over a 3‐yr period. Leaching of particulate P (PP) was significantly less from clay soil columns with lime than from clay soil columns without (P < 0.001 andP < 0.05, respectively), with a relative reduction of 49 and 51% in the two soils. Leaching of dissolved reactive P (DRP) was less from sand columns with lime than from sand columns without, although not significantly so due to large variation in P leaching between columns. These results indicate that placement of lime on subsoil has potential to reduce P leaching, especially ofPPfrom clay soils. However, more studies including both topsoil and subsoil and a range of soil types are needed to assess the full potential of this P mitigation option.
DNA‐binding and repressor function are prerequisites for the turnover of the tomato heat stress transcription factor HsfB1
Authors: Röth Sascha , Mirus Oliver , Bublak Daniela , Scharf Klaus‐Dieter , Schleiff Enrico
Published: August 2016

HsfB1 is a central regulator of heat stress (HS) response and functions dually as a transcriptional co‐activator of HsfA1a and a general repressor in tomato. HsfB1 is efficiently synthesized during the onset of HS and rapidly removed in the course of attenuation during the recovery phase. Initial results point to a complex regime modulating HsfB1 abundance involving the molecular chaperone Hsp90. However, the molecular determinants affecting HsfB1 stability needed to be established. We provide experimental evidence that DNA‐bound HsfB1 is efficiently targeted for degradation when active as a transcriptional repressor. Manipulation of the DNA‐binding affinity by mutating the HsfB1 DNA‐binding domain directly influences the stability of the transcription factor. During HS, HsfB1 is stabilized, probably due to co‐activator complex formation with HsfA1a. The process of HsfB1 degradation involves nuclear localized Hsp90. The molecular determinants of HsfB1 turnover identified in here are so far seemingly unique. A mutational switch of the R/KLFGV repressor motif's arginine and lysine implies that the abundance of other R/KLFGV type Hsfs, if not other transcription factors as well, might be modulated by a comparable mechanism. Thus, we propose a versatile mechanism for strict abundance control of the stress‐induced transcription factor HsfB1 for the recovery phase, and this mechanism constitutes a form of transcription factor removal from promoters by degradation inside the nucleus.
Distinct roles of the two VPS33 proteins in the endolysosomal system in Caenorhabditis elegans
Authors: Gengyo‐Ando Keiko , Kage‐Nakadai Eriko , Yoshina Sawako , Otori Muneyoshi , Kagawa‐Nagamura Yuko , Nakai Junichi , Mitani Shohei
Published: August 2016

Sec1/Munc‐18 (SM) family proteins are essential regulators in intracellular transport in eukaryotic cells. The SM protein Vps33 functions as a core subunit of two tethering complexes, class C core vacuole/endosome tethering (CORVET) and homotypic fusion and vacuole protein sorting (HOPS) in the endocytic pathway in yeast. Metazoan cells possess two Vps33 proteins, VPS33A and VPS33B, but their precise roles remain unknown. Here, we present a comparative analysis of Caenorhabditis elegans null mutants for these proteins. We found that the vps‐33.1 (VPS33A) mutants exhibited severe defects in both endocytic function and endolysosomal biogenesis in scavenger cells. Furthermore, vps‐33.1 mutations caused endocytosis defects in other tissues, and the loss of maternal and zygotic VPS‐33.1 resulted in embryonic lethality. By contrast, vps‐33.2 mutants were viable but sterile, with terminally arrested spermatocytes. The spermatogenesis phenotype suggests that VPS33.2 is involved in the formation of a sperm‐specific organelle. The endocytosis defect in the vps‐33.1 mutant was not restored by the expression of VPS‐33.2, which indicates that these proteins have nonredundant functions. Together, our data suggest that VPS‐33.1 shares most of the general functions of yeast Vps33 in terms of tethering complexes in the endolysosomal system, whereas VPS‐33.2 has tissue/organelle specific functions in C. elegans.
Use of an Absorbable Urethral Stent for the Management of a Urethral Stricture in a Stallion
Authors: Trela Jan M. , Dechant Julie E. , Culp William T. , Whitcomb Mary B. , Palm Carrie A. , Nieto Jorge E.
Published: August 2016

Objective

To describe the successful management of a urethral stricture with an absorbable stent in a stallion.

Study Design

Clinical report.

Animals

Stallion with a urethral stricture.

Results

A 12‐year‐old Thoroughbred breeding stallion was evaluated for acute onset of colic. Uroperitoneum because of presumptive urinary bladder rupture, with urethral obstruction by a urethrolith, was diagnosed. The uroperitoneum was treated conservatively. The urethrolith was removed through a perineal urethrotomy. Approximately 15 weeks after urethrolith removal, the stallion presented with a urethral stricture. The stricture was unsuccessfully treated with an indwelling urinary catheter and 4 attempts at balloon dilation. Eight weeks after diagnosis of stricture, an absorbable polydioxanone (20 mm × 80 mm) urethral stent was implanted under percutaneous, ultrasound guidance. Urethroscopy was performed at 70, 155, and 230 days after stent placement and the endoscope passed through the affected site without complication. Urethroscopy at 155 days showed the stent had been reabsorbed. Follow‐up 20 months after stent placement reports the stallion was able to void a normal urine stream.

Conclusions

Absorbable urethral stent placement was a feasible treatment for urethral stricture in this stallion.
COP21 Management: How to Link up International Governance with National Policy-implementation
Authors: Lane Jan-Erik
Published: August 2016

It seems scientifically legitimate to move beyond the natural sciences' perspective upon he COP21 project. Can really social science theory be mustered to manage this global project for such a long time span? Or is it all make belief, decarbonisation writ large a figment of imagination? The natural sciences can deliver predictions about emissions and temperature as well as their interconnections. But only economics and social science have knowledge that is relevant to the implementation of the three goals of decarbonisation, subject to the requirement of economic growth. Neither implementation theory nor the management approach would render COP21 much chance of success. To understand COP21 management, one must analyse the country situations with regard to GDP-GHG(CO2) links as well as the mix of energy sources in each country.
A Parametrically Broadband Nonlinear Energy Harvester
Authors: Yildirim Tanju , Ghayesh Mergen H. , Searle Thomas , Li Weihua , Alici Gursel
Published: August 2016

In this work, for the first time, an energy harvester based on the nonlinear dynamical response of a parametrically excited cantilever beam in contact with mechanical stoppers has been fabricated and tested; a 145% increase in the bandwidth at which energy can be effectively harvested has been observed. Experimental and theoretical investigations have been performed in order to assess the increased operating bandwidth of the energy harvester fabricated; for the experimental investigations, an electrodynamic shaker connected to a shaking table has been used to parametrically stimulate the energy harvesting device. Results showed that the parametric energy harvester without stoppers displayed a weak softening-type nonlinear response; however, with the addition of mechanical stoppers the energy harvester displayed a strong hardening-type nonlinear response which is ideal for capturing kinetic energy over larger bandwidths. The addition of mechanical stoppers on a parametrically excited cantilever beam has significant qualitative and quantitative effects on the nonlinear parametric energy harvesting; the energy harvesting bandwidth was increased in the range of 35–145% by adjusting the stoppers.
Effect of Curvature on Penetration Resistance of Polycarbonate Panels
Authors: Antoine G. O. , Batra R. C.
Published: August 2016

Three-dimensional transient deformations of clamped flat and doubly curved polycarbonate (PC) panels impacted by a rigid smooth hemispherical-nosed circular cylinder have been numerically studied by the finite-element (FE) method to delineate effects of the panel radius of curvature to its thickness ratio on their penetration resistance. The PC is modeled as thermoelastoviscoplastic with the effective plastic strain rate depending upon the hydrostatic pressure. The effective plastic strain of 3.0 at failure is ascertained by matching for one set of flat panels the computed and the experimental minimum perforation speeds. It is found that a negative curvature (i.e., the center of curvature toward the impactor) of a panel degrades its penetration performance, and the positive curvature enhances it especially for thin panels with thickness/radius of curvature of 0.01. However, the benefit is less evident for panels with the panel thickness/radius of curvature of 0.04 or more. For positively curved thin panels, an elastic hinge forms around the central impacted area during an early stage of deformations, and subsequent deformations occur within this region. No such hinge is observed for flat plates, negatively curved panels of all the thicknesses, and positively curved thick panels. Furthermore, the maximum effective stress induced in regions surrounding the impacted area is less for positively curved panels than that for flat panels. The dominant failure mechanism is found to be the deletion of failed elements due to the effective plastic strain in them exceeding 3.0 rather than due to plug formation. For an example problem, the dependence of the effective plastic strain rate upon the hydrostatic pressure and the consideration of the Coulomb friction at the contact surfaces exhibited minimal effects on the penetration characteristics. This information should be useful for designers of impact-resistant transparent armor, such as an airplane canopy, automobile windshield, and goggles.
Miniature Viscous Disk Pump: Performance Variations From Non-Newtonian Elastic Turbulence
Authors: Ligrani Phil , Lund Benjamin , Fatemi Arshia
Published: August 2016

Within the present investigation, a miniature viscous disk pump (VDP) is utilized to characterize and quantify non-Newtonian fluid elastic turbulence effects, relative to Newtonian flow behavior. Such deviations from Newtonian behavior are induced by adding polyacrylamide to purified water. The VDP consists of a 10.16 mm diameter disk that rotates above a C-shaped channel with inner and outer radii of 1.19 mm and 2.38 mm, respectively. A channel depth of 230 μm is employed. Fluid inlet and outlet ports are located at the ends of the C-shaped channel. Experimental data are given for rotational speeds of 126 1/s, 188 1/s, 262 1/s, and 366 1/s, pressure rises as high as 700 Pa, and flow rates up to approximately 0.00000005 m3/s. Reynolds number ranges from 2.9 to 6.5 for the non-Newtonian polyacrylamide solution flows and from 51.6 to 149.8 for the Newtonian pure water flows. To characterize deviations due to non-Newtonian elastic turbulence phenomena, two new parameters are introduced, PrR and HCR, where HCR is the ratio of head coefficient (HC) for the polyacrylamide solution and head coefficient for the water solution, and PrR is the ratio of pump power for the polyacrylamide solution and pump power for the water solution. Relative to Newtonian, pure water flows, the polyacrylamide solution flows give pump head coefficient data, dimensional pressure rise data, slip coefficients (SCs), specific speed (SS) values, and dimensional power data, which show significant variations and differences as they vary with flow coefficient (FC) or dimensional volumetric flow rate. Also important are different ranges of specific speed (SS) for the pure water and polyacrylamide solutions, and a lower range of SC or slip coefficient values for the polyacrylamide solution flows, compared to the pure water flows. These variations are due to increased elastic turbulence losses, which occur as viscosity magnitudes increase and the elastic polymers are excited by mechanical stress, which causes them to extend, deform, stretch, and intertwine.
Conduction and rectification in NbOx- and NiO-based metal-insulator-metal diodes
Authors: Osgood Richard M. , Giardini Stephen , Carlson Joel , Periasamy Prakash , Guthrey Harvey , O'Hayre Ryan , Chin Matthew , Nichols Barbara , Dubey Madan , Fernandes Gustavo , Kim Jin Ho , Xu Jimmy , Parilla Philip , Berry Joseph , Ginley David
Published: August 2016

Conduction and rectification in nanoantenna-coupled NbOx- and NiO-based metal-insulator-metal (MIM) diodes (“nanorectennas”) are studied by comparing new theoretical predictions with the measured response of nanorectenna arrays. A new quantum mechanical model is reported and agrees with measurements of current–voltage (I–V) curves, over 10 orders of magnitude in current density, from [NbOx(native)-Nb2O5]- and NiO-based samples with oxide thicknesses in the range of 5–36 nm. The model, which introduces new physics and features, including temperature, electron effective mass, and image potential effects using the pseudobarrier technique, improves upon widely used earlier models, calculates the MIM diode's I–V curve, and predicts quantitatively the rectification responsivity of high frequency voltages generated in a coupled nanoantenna array by visible/near-infrared light. The model applies both at the higher frequencies, when high-energy photons are incident, and at lower frequencies, when the formula for classical rectification, involving derivatives of the I–V curve, may be used. The rectified low-frequency direct current is well-predicted in this work's model, but not by fitting the experimentally measured I–V curve with a polynomial or by using the older Simmons model (as shown herein). By fitting the measured I–V curves with our model, the barrier heights in Nb-(NbOx(native)-Nb2O5)-Pt and Ni-NiO-Ti/Ag diodes are found to be 0.41/0.77 and 0.38/0.39 eV, respectively, similar to literature reports, but with effective mass much lower than the free space value. The NbOx (native)-Nb2O5 dielectric properties improve, and the effective Pt-Nb2O5 barrier height increases as the oxide thickness increases. An observation of direct current of ∼4 nA for normally incident, focused 514 nm continuous wave laser beams are reported, similar in magnitude to recent reports. This measured direct current is compared to the prediction for rectified direct current, given by the rectification responsivity, calculated from the I–V curve times input power.
Acoustic time‐of‐flight for proton range verification in water
Authors: Jones Kevin C. , Vander Stappen François , Sehgal Chandra M. , Avery Stephen
Published: August 2016

Purpose:

Measurement of the arrival times of thermoacoustic waves induced by pulsed proton dose depositions (protoacoustics) may provide a proton range verification method. The goal of this study is to characterize the required dose and protoacoustic proton range (distance) verification accuracy in a homogeneous water medium at a hospital‐based clinical cyclotron.

Methods:

Gaussian‐like proton pulses with 17 μs widths and instantaneous currents of 480 nA (5.6 × 107 protons/pulse, 3.4 cGy/pulse at the Bragg peak) were generated by modulating the cyclotron proton source with a function generator. After energy degradation, the 190 MeV proton pulses irradiated a water phantom, and the generated protoacoustic emissions were measured by a hydrophone. The detector position and proton pulse characteristics were varied. The experimental results were compared to simulations. Different arrival time metrics derived from acoustic waveforms were compared, and the accuracy of protoacoustic time‐of‐flight distance calculations was assessed.

Results:

A 27 mPa noise level was observed in the treatment room during irradiation. At 5 cm from the proton beam, an average maximum pressure of 5.2 mPa/1 × 107 protons (6.1 mGy at the Bragg peak) was measured after irradiation with a proton pulse with 10%–90% rise time of 11 μs. Simulation and experiment arrival times agreed well, and the observed 2.4 μs delay between simulation and experiment is attributed to the difference between the hydrophone's acoustic and geometric centers. Based on protoacoustic arrival times, the beam axis position was measured to within (x, y) = (−2.0,  0.5) ± 1 mm. After deconvolution of the exciting proton pulse, the protoacoustic compression peak provided the most consistent measure of the distance to the Bragg peak, with an error distribution with mean = − 4.5 mm and standard deviation = 2.0 mm.

Conclusions:

Based on water tank measurements at a clinical hospital‐based cyclotron, protoacoustics is a potential method for measuring the beam's position (x and y within 2.0 mm) and Bragg peak range (2.0 mm standard deviation), although range verification will require simulation or experimental calibration to remove systematic error. Based on extrapolation, a protoacoustic arrival time reproducibility of 1.5 μs (2.2 mm) is achievable with 2 Gy of total deposited dose. Of the compared methods, deconvolution of the excitation proton pulse is the best technique for extracting protoacoustic arrival times, particularly if there is variation in the proton pulse shape.
Noise suppressed partial volume correction for cardiac SPECT/CT
Authors: Chan Chung , Liu Hui , Grobshtein Yariv , Stacy Mitchel R. , Sinusas Albert J. , Liu Chi
Published: August 2016

Purpose:

Partial volume correction (PVC) methods typically improve quantification at the expense of increased image noise and reduced reproducibility. In this study, the authors developed a novel voxel‐based PVC method that incorporates anatomical knowledge to improve quantification while suppressing noise for cardiac SPECT/CT imaging.

Methods:

In the proposed method, the SPECT images were first reconstructed using anatomical‐based maximum a posteriori (AMAP) with Bowsher's prior to penalize noise while preserving boundaries. A sequential voxel‐by‐voxel PVC approach (Yang's method) was then applied on the AMAP reconstruction using a template response. This template response was obtained by forward projecting a template derived from a contrast‐enhanced CT image, and then reconstructed using AMAP to model the partial volume effects (PVEs) introduced by both the system resolution and the smoothing applied during reconstruction. To evaluate the proposed noise suppressed PVC (NS‐PVC), the authors first simulated two types of cardiac SPECT studies: a 99mTc‐tetrofosmin myocardial perfusion scan and a 99mTc‐labeled red blood cell (RBC) scan on a dedicated cardiac multiple pinhole SPECT/CT at both high and low count levels. The authors then applied the proposed method on a canine equilibrium blood pool study following injection with 99mTc‐RBCs at different count levels by rebinning the list‐mode data into shorter acquisitions. The proposed method was compared to MLEM reconstruction without PVC, two conventional PVC methods, including Yang's method and multitarget correction (MTC) applied on the MLEM reconstruction, and AMAP reconstruction without PVC.

Results:

The results showed that the Yang's method improved quantification, however, yielded increased noise and reduced reproducibility in the regions with higher activity. MTC corrected for PVE on high count data with amplified noise, although yielded the worst performance among all the methods tested on low‐count data. AMAP effectively suppressed noise and reduced the spill‐in effect in the low activity regions. However it was unable to reduce the spill‐out effect in high activity regions. NS‐PVC yielded superior performance in terms of both quantitative assessment and visual image quality while improving reproducibility.

Conclusions:

The results suggest that NS‐PVC may be a promising PVC algorithm for application in low‐dose protocols, and in gated and dynamic cardiac studies with low counts.
Role of contextual cues on the perception of spectrally reduced interrupted speech
Authors: Patro Chhayakanta , Mendel Lisa Lucks
Published: August 2016

Understanding speech within an auditory scene is constantly challenged by interfering noise in suboptimal listening environments when noise hinders the continuity of the speech stream. In such instances, a typical auditory-cognitive system perceptually integrates available speech information and “fills in” missing information in the light of semantic context. However, individuals with cochlear implants (CIs) find it difficult and effortful to understand interrupted speech compared to their normal hearing counterparts. This inefficiency in perceptual integration of speech could be attributed to further degradations in the spectral-temporal domain imposed by CIs making it difficult to utilize the contextual evidence effectively. To address these issues, 20 normal hearing adults listened to speech that was spectrally reduced and spectrally reduced interrupted in a manner similar to CI processing. The Revised Speech Perception in Noise test, which includes contextually rich and contextually poor sentences, was used to evaluate the influence of semantic context on speech perception. Results indicated that listeners benefited more from semantic context when they listened to spectrally reduced speech alone. For the spectrally reduced interrupted speech, contextual information was not as helpful under significant spectral reductions, but became beneficial as the spectral resolution improved. These results suggest top-down processing facilitates speech perception up to a point, and it fails to facilitate speech understanding when the speech signals are significantly degraded.
The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs
Authors: Lee Hyunwook , Shingler Kristin L. , Organtini Lindsey J. , Ashley Robert E. , Makhov Alexander M. , Conway James F. , Hafenstein Susan
Published: August 2016

Nanodiscs used as a mock membrane captured a picornavirus undergoing global and local changes to enter host cells.
Anthropocene pinned to postwar period
Authors: Voosen Paul
Published: August 2016

Geologists vote to seek a “golden spike,” but push for formal acceptance faces skepticism
Europe's new hepatitis problem
Authors: Kupferschmidt Kai
Published: August 2016

Many get infected with hepatitis E, and a few get very sick. How can the virus be stopped?
Targeting health subsidies through a nonprice mechanism: A randomized controlled trial in Kenya
Authors: Dupas Pascaline , Hoffmann Vivian , Kremer Michael , Zwane Alix Peterson
Published: August 2016

Delivering chlorine to those who use it

In developed countries, a consumer's valuation of a health product can be measured by his or her willingness to pay for it. But poorer individuals, especially those in developing countries, might want and need a product yet be unable to pay for it with money. Dupaset al.demonstrate that a nonprice voucher mechanism can be used to deliver chlorine for water treatment to people in Kenya who are too poor to pay for it, but who use it when they get it (see the Perspective by Olken). Having to redeem the vouchers screens out people who would accept the free chlorine solution but not use it.

Science, this issue p.889; see also p.864
Teleseismic
S
wave microseisms
Authors: Nishida Kiwamu , Takagi Ryota
Published: August 2016

A seismic “weather bomb” detector

Seismic tomography is like an x-ray of Earth's interior, except that it uses earthquakes for the illumination. Earthquakes are imperfect illuminators because they are clustered on plate boundaries, leaving much of the interior in the shadows. Using a seismic array in Japan, Nishida and Takagi detected seismic waves that they attribute to a severe and distant North Atlantic storm called a “weather bomb” (see the Perspective by Gerstoft and Bromirski). The seismic energy traveling from weather bombs through the Earth appears to be capable of illuminating the many dark patches of Earth's interior.

Science
, this issue p.
919
; see also p.
869
Information leverage in interconnected ecosystems: Overcoming the curse of dimensionality
Authors: Ye Hao , Sugihara George
Published: August 2016

Harnessing complexity in ecology

Ecology concerns the behavior of complex, dynamic, interconnected systems of populations, communities, and ecosystems over time. Yet ecological time series can be relatively short, owing to practical limits on study duration. Ye and Sugihara introduce an analytical approach called multiview embedding, which harnesses the complexity of short, noisy time series that are common in ecology and other disciplines such as economics. Using examples from published data sets, they show how this approach enhances the tractability of complex data from multiple interacting components and offers a way forward in ecological forecasting.

Science
, this issue p.
922
“Weather bomb” induced seismic signals
Authors: Gerstoft Peter , Bromirski Peter D.
Published: August 2016

Seismic waves generated by intense storms can reveal details of Earth's interior
Building molecular complexity from scratch
Authors: Verdaguer Xavier
Published: August 2016

The Pauson-Khand cycloaddition reaction builds the tetracyclic core of (+)-ryanodol
Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications
Authors: Avettand-Fènoël Véronique , Hocqueloux Laurent , Ghosn Jade , Cheret Antoine , Frange Pierre , Melard Adeline , Viard Jean-Paul , Rouzioux Christine
Published: August 2016

HIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis.
Navigating Microbiological Food Safety in the Era of Whole-Genome Sequencing
Authors: Ronholm J. , Nasheri Neda , Petronella Nicholas , Pagotto Franco
Published: August 2016

The epidemiological investigation of a foodborne outbreak, including identification of related cases, source attribution, and development of intervention strategies, relies heavily on the ability to subtype the etiological agent at a high enough resolution to differentiate related from nonrelated cases. Historically, several different molecular subtyping methods have been used for this purpose; however, emerging techniques, such as single nucleotide polymorphism (SNP)-based techniques, that use whole-genome sequencing (WGS) offer a resolution that was previously not possible. With WGS, unlike traditional subtyping methods that lack complete information, data can be used to elucidate phylogenetic relationships and disease-causing lineages can be tracked and monitored over time. The subtyping resolution and evolutionary context provided by WGS data allow investigators to connect related illnesses that would be missed by traditional techniques. The added advantage of data generated by WGS is that these data can also be used for secondary analyses, such as virulence gene detection, antibiotic resistance gene profiling, synteny comparisons, mobile genetic element identification, and geographic attribution. In addition, several software packages are now available to generate
in silico
results for traditional molecular subtyping methods from the whole-genome sequence, allowing for efficient comparison with historical databases. Metagenomic approaches using next-generation sequencing have also been successful in the detection of nonculturable foodborne pathogens. This review addresses state-of-the-art techniques in microbial WGS and analysis and then discusses how this technology can be used to help support food safety investigations. Retrospective outbreak investigations using WGS are presented to provide organism-specific examples of the benefits, and challenges, associated with WGS in comparison to traditional molecular subtyping techniques.
Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination
Authors: Levine Min Z. , Martin Judith M. , Gross F. Liaini , Jefferson Stacie , Cole Kelly Stefano , Archibald Crystal Ann , Nowalk Mary Patricia , Susick Michael , Moehling Krissy , Spencer Sarah , Chung Jessie R. , Flannery Brendan , Zimmerman Richard K.
Published: August 2016

Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure.
Real-Time Genome Sequencing of Resistant Bacteria Provides Precision Infection Control in an Institutional Setting
Authors: Mellmann Alexander , Bletz Stefan , Böking Thomas , Kipp Frank , Becker Karsten , Schultes Anja , Prior Karola , Harmsen Dag
Published: August 2016

The increasing prevalence of multidrug-resistant (MDR) bacteria is a serious global challenge. Here, we studied prospectively whether bacterial whole-genome sequencing (WGS) for real-time MDR surveillance is technical feasible, returns actionable results, and is cost-beneficial. WGS was applied to all MDR isolates of four species (methicillin-resistant
Staphylococcus aureus
[MRSA], vancomycin-resistant
Enterococcus faecium
, MDR
Escherichia coli
, and MDR
Pseudomonas aeruginosa
) at the University Hospital Muenster, Muenster, Germany, a tertiary care hospital with 1,450 beds, during two 6-month intervals. Turnaround times (TAT) were measured, and total costs for sequencing per isolate were calculated. After cancelling prior policies of preemptive isolation of patients harboring certain Gram-negative MDR bacteria in risk areas, the second interval was conducted. During interval I, 645 bacterial isolates were sequenced. From culture, TATs ranged from 4.4 to 5.3 days, and costs were €202.49 per isolate. During interval II, 550 bacterial isolates were sequenced. Hospital-wide transmission rates of the two most common species (MRSA and MDR
E. coli
) were low during interval I (5.8% and 2.3%, respectively) and interval II (4.3% and 5.0%, respectively). Cancellation of isolation of patients infected with non-pan-resistant MDR
E. coli
in risk wards did not increase transmission. Comparing sequencing costs with avoided costs mostly due to fewer blocked beds during interval II, we saved in excess of €200,000. Real-time microbial WGS in our institution was feasible, produced precise actionable results, helped us to monitor transmission rates that remained low following a modification in isolation procedures, and ultimately saved costs.
Molecular Characteristics of Group B Streptococci Isolated from Adults with Invasive Infections in Japan
Authors: Morozumi Miyuki , Wajima Takeaki , Takata Misako , Iwata Satoshi , Ubukata Kimiko
Published: August 2016

Streptococcus agalactiae
(group B streptococcus) isolates (
n
= 443) obtained from Japanese adults with invasive infections between April 2010 and March 2013 were analyzed for capsular serotype, multilocus sequence type (ST), antibiotic susceptibility, and resistance genes. Among these cases, bacteremia without primary focus was the most common variety of infection (49.9%), followed by cellulitis (12.9%) and pneumonia (9.0%). Concerning patient age (18 to 59, 60 to 69, 70 to 79, 80 to 89, and 90 years old or older), the incidence of pneumonia increased in patients in their 70s and 80s (
P
< 0.001), while younger patients (18 to 59 and 60 to 69 years old) were more likely to have abscesses (
P
< 0.05). The mortality rate was 10.2% for all ages. The most common capsular serotype was Ib (39.5%), followed by V (16.0%), III (13.8%), VI (9.5%), and Ia (8.6%). The main ST of serotype Ib strains was ST10, which belonged to clonal complex 10 (88.0%). The predominant clonal complexes of serotypes V and III, respectively, were 1 (78.9%) and 19 (75.4%). Among these isolates, 9 strains (2.0%) were identified as group B streptococci with reduced penicillin susceptibility, reflecting amino acid substitutions in penicillin-binding protein 2X (PBP2X). In addition, 19.2% of all strains possessed
mef
(A/E),
erm
(A), or
erm
(B) genes, which mediate macrolide resistance, while 40.2% of strains were resistant to quinolones resulting from amino acid substitutions in GyrA and ParC. Our data argue strongly for the continuous surveillance of microbial characteristics and judicious antibiotic use in clinical practice.
Cerebrospinal Fluid (1,3)-Beta-
d
-Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis
Authors: Stevens David A. , Zhang Yonglong , Finkelman Malcolm A. , Pappagianis Demosthenes , Clemons Karl V. , Martinez Marife
Published: August 2016

Diagnosing coccidioidal meningitis (CM) can be problematic owing to its infrequency and/or a delay in the positivity of a cerebrospinal fluid (CSF) culture or CSF antibody, particularly if the primary coccidioidal infection is unrecognized. We tested 37 CSF specimens, 26 from patients with confirmed CM and 11 from patients with suspected microbial meningitis without fungal diagnosis, for (1,3)-beta-glucan (BG). BG in CM CSF specimens ranged from 18 to 3,300 pg/ml and in controls ranged from <3.9 to 103 pg/ml. Diagnostic performance was determined using a 31-pg/ml cutoff (the bottom of the serum range according to the directions for the commercial kit, although further serial dilutions of the standard indicated linearity to 3.9). Sensitivity was 96%, specificity was 82%, positive and negative predictive values were 93% and 90%, and the area under the receiver operating characteristic curve was 0.937. Fifteen of 15 samples of >103 pg/ml were CM. The one false-negative specimen was from a patient with a pseudosyrinx, without inflammatory evidence of meningitis activity. Serial samples from some patients were positive at ≤8 years, indicating no loss of positivity with chronicity. Samples stored frozen since 2000 included those with 2 of the 3 highest values, indicating that fresh samples not required. A previous study indicated serum sensitivities of 53% in acute, 50% in resolved, and 83% in disseminated and meningeal coccidioidomycosis. Three studies of other fungal meningitides ranged from 86 to 1,524 pg/ml CSF, with 37 controls of <4 to 115 pg/ml CSF. CSF BG analysis had good diagnostic performance in CM. CSF BG testing can be useful in CM, and a commercial kit is available. It will be of interest to correlate this with course, treatment, outcome, inflammation, and antigen. The only mycoses with common central nervous system (CNS) involvement are cryptococcal and coccidioidal, so CSF BG screening can be useful in meningitis diagnosis.
Characterization of Clade 7.2 H5 Avian Influenza Viruses That Continue To Circulate in Chickens in China
Authors: Liu Liling , Zeng Xianying , Chen Pucheng , Deng Guohua , Li Yanbing , Shi Jianzhong , Gu Chunyang , Kong Huihui , Suzuki Yasuo , Jiang Yongping , Tian Guobin , Chen Hualan
Published: August 2016

The H5N1 avian influenza viruses emerged in Southeast Asia in the late 20th century and have evolved into multiple phylogenetic clades based on their hemagglutinin (HA)-encoding genes. The clade 7.2 viruses were first detected in chickens in northern China in 2006, and vaccines specifically targeted to the clade were developed and have been used in poultry in China since 2006. During routine surveillance and disease diagnosis, we isolated seven H5 viruses between 2011 and 2014 that bear the clade 7.2 HA genes. Here, we performed extensive studies to understand how the clade 7.2 H5 viruses have evolved in chickens in China. Full genome sequence analysis revealed that the seven viruses formed two subtypes (four H5N1 viruses and three H5N2 viruses) and four genotypes by deriving genes from other influenza viruses. All of the viruses had antigenically drifted from the clade 7.2 viruses that were isolated in 2006. Pathogenicity studies of four viruses, one from each genotype, revealed that all of the viruses are highly pathogenic in chickens, but none of them could replicate in ducks. The four viruses exclusively bound to avian-type receptors and replicated only in the turbinates and/or lungs of mice; none of them were lethal to mice at a dosage of 10
6
50% egg infective doses (EID
50
). Our study indicates that although the clade 7.2 viruses have not been eradicated from poultry through vaccination, they have not become more dangerous to other animals (e.g., ducks and mice) and humans.

IMPORTANCE
Animal influenza viruses can acquire the ability to infect and kill humans. The H5N1 viruses have been a concern in recent decades because of their clear pandemic potential. We sorted H5N1 influenza viruses into different phylogenetic clades based on their HA genes. The clade 7.2 viruses were detected in chickens in several provinces of northern China in 2006. Vaccines for these viruses were subsequently developed and have been used ever since to control infection of poultry. Here, we analyzed the genetic and biologic properties of seven clade 7.2 viruses that were isolated from chickens between 2011 and 2014. We found that after nearly 9 years of circulation in chickens, the clade 7.2 viruses still exclusively bind to avian-type receptors and are of low pathogenicity to mice, suggesting that these H5 viruses pose a low risk to human public health.