bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal Recall Error in Retrospectively Reported Time‐to‐Pregnancy: an Assessment and Bias Analysis
Authors: Radin Rose G. , Rothman Kenneth J. , Hatch Elizabeth E. , Mikkelsen Ellen M. , Sorensen Henrik T. , Riis Anders H. , Fox Matthew P. , Wise Lauren A.
Published: October 2015

Background

Epidemiologic studies of fecundability often use retrospectively measured time‐to‐pregnancy (TTP), thereby introducing potential for recall error. Little is known about how recall error affects the bias and precision of the fecundability odds ratio (FOR) in such studies.

Methods

Using data from the Danish Snart‐Gravid Study (2007–12), we quantified error for TTP recalled in the first trimester of pregnancy relative to prospectively measured TTP among 421 women who enrolled at the start of their pregnancy attempt and became pregnant within 12 months. We defined recall error as retrospectively measured TTP minus prospectively measured TTP. Using linear regression, we assessed mean differences in recall error by maternal characteristics. We evaluated the resulting bias in the FOR and 95% confidence interval (CI) using simulation analyses that compared corrected and uncorrected retrospectively measured TTP values.

Results

Recall error (mean = −0.11 months, 95% CI −0.25, 0.04) was not appreciably associated with maternal age, gravidity, or recent oral contraceptive use. Women with TTP > 2 months were more likely to underestimate their TTP than women with TTP ≤ 2 months (unadjusted mean difference in error: −0.40 months, 95% CI −0.71, −0.09). FORs of recent oral contraceptive use calculated from prospectively measured, retrospectively measured, and corrected TTPs were 0.82 (95% CI 0.67, 0.99), 0.74 (95% CI 0.61, 0.90), and 0.77 (95% CI 0.62, 0.96), respectively.

Conclusions

Recall error was small on average among pregnancy planners who became pregnant within 12 months. Recall error biased the FOR of recent oral contraceptive use away from the null by 10%. Quantitative bias analysis of the FOR can help researchers quantify the bias from recall error.
Comparison of Whole Ovary Cryotreatments for Fertility Preservation
Authors: Lotz L , Hauenstein T , Nichols‐Burns SM , Strissel P , Hoffmann I , Findeklee S , Dittrich R , Beckmann MW , Oppelt PG
Published: October 2015

Contents

The goal of this study was to compare a traditional slow‐freeze method (TF) with an open unidirectional slow freeze cooling system (UF) for whole ovary cryopreservation. Therefore, whole pig ovaries were randomly assigned to (A) fresh control, (B) traditional slow freeze (TF) or (C) unidirectional slow freeze (UF). Ovaries were perfused with 10% DMSO in Krebs‐Ringer. For TF, whole ovaries were placed in specimen jars containing 10% DMSO and placed into a specialized container for freezing filled with propan‐2‐ol. For UF, whole ovaries were placed within a specially designed container containing 10% DMSO and transferred to a specialized freezing machine (CTE 920). Histological evaluation demonstrated intact morphology of follicles in all groups; however, an overall decrease of follicle numbers in TF (46%) and UF (50%) compared to fresh control. Live/dead assay indicated significantly lower populations of live cells in both TF (60%) and UF (58%) compared to fresh tissue (74%). TUNEL assay confirmed a difference in percentage of apoptotic follicles between fresh and TF, but there was no significant difference between fresh and UF. To improve the structural and functional integrity of whole ovaries, further investigation, especially into directional freezing, is needed. Whole ovary cryopreservation could provide opportunities for women facing fertility loss due to chemo‐ or radiotherapy treatment.
Fertility in Adult Bitches Previously Treated with a 4.7 mg Subcutaneous Deslorelin Implant
Authors: Borges P , Fontaine E , Maenhoudt C , Payan‐Carreira R , Santos N , Leblond E , Fontaine C , Fontbonne A
Published: October 2015

Content

The absence of fertility problems in male dogs after a single treatment with deslorelin acetate (Suprelorin®) is well acknowledged. However, reports on the application of deslorelin in the bitch and information concerning fertility after implant treatment are still limited. In this retrospective study, data concerning induced and spontaneous oestruses of 39 bitches from 17 breeds, treated with deslorelin acetate implants (4.7 mg Suprelorin®, Virbac, France), were retrieved to assess post‐treatment fertility (ovulation rate, pregnancy rate and litter size). Animals were grouped according to treatment characteristics: group 1 (Gr1) – females submitted to oestrus induction, showing natural oestruses afterwards (n = 19); group 2 (Gr2) – females re‐implanted with 4.7 mg deslorelin acetate to re‐induce oestrus, showing subsequent spontaneous post‐implant oestruses (n = 7); and group 3 (Gr3) – females submitted to a 4.7 mg deslorelin acetate implant for oestrus suppression, evaluated at subsequent spontaneous post‐implant oestruses (n = 13). Comparison of fertility traits between induced and post‐treatment spontaneous oestruses in Gr1 and Gr2 (short treatments), or between spontaneous oestruses after long‐treatment schedules (Gr 3) revealed a slightly better performance in spontaneous cycles compared with induced cycles: ovulation rate post‐treatment was 97.1%, 94.1% and 94.4% and the pregnancy rate post‐treatment was 91.2%, 88.9% and 84.6% for groups 1, 2 and 3, respectively. Nevertheless, fertility in induced and post‐treatment oestruses was considered normal. Moreover, the individual litter size did not differ within groups between induced and spontaneous cycles. From these findings, we concluded that treatment with 4.7 mg deslorelin implants did not compromise the bitches' fertility in subsequent oestruses.
Differences in baseline factors and survival between normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis in COPD exacerbation: A pilot study
Authors: Lun Chung‐Tat , Tsui Miranda S.N. , Cheng Suet‐Lai , Chan Veronica L. , Leung Wah‐Shing , Cheung Alice P.S. , Chu Chung‐Ming
Published: October 2015

Background and objective

Patients with chronic obstructive pulmonary disease (COPD) experiencing acute exacerbation (AE‐COPD) with decompensated respiratory acidosis are known to have poor outcomes in terms of recurrent respiratory failure and death. However, the outcomes of AE‐COPD patients with compensated respiratory acidosis are not known.

Methods

We performed a 1‐year prospective, single‐centre, cohort study in patients surviving the index admission for AE‐COPD to compare baseline factors between groups with normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis. Survival analysis was done to examine time to readmissions, life‐threatening events and death.

Results

A total of 250 patients fulfilling the inclusion and exclusion criteria were recruited and 245 patients were analysed. Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with lower FEV1 % (P < 0.001), higher GOLD stage (P = 0.003, <0.001) and higher BODE index (P = 0.038, 0.001) and a shorter time to life‐threatening events (P < 0.001). Comparing compensated and decompensated respiratory acidosis, there was no difference in FEV1 (% predicted) (P = 0.15), GOLD stage (P = 0.091), BODE index (P = 0.158) or time to life‐threatening events (P = 0.301). High PaCO2 level (P = 0.002) and previous use of non‐invasive ventilation (NIV) in acute setting (P < 0.001) are predictive factors of future life‐threatening events by multivariate analysis.

Conclusions

Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with poorer lung function and higher risk of future life‐threatening events. High PaCO2 level and past history of NIV use in acute settings were predictive factors for future life‐threatening events. Compensated respiratory acidosis warrants special attention and optimization of medical therapy as it poses risk of life‐threatening events.
The Effect of Low‐Level Laser Therapy on the Healing of Open Wounds in Dogs
Authors: Kurach Lindsey M. , Stanley Bryden J. , Gazzola Krista M. , Fritz Michele C. , Steficek Barbara A. , Hauptman Joe G. , Seymour Kristen J.
Published: October 2015

Objective

To evaluate the effects of low‐level laser therapy (LLLT) on acute, full‐thickness wound healing in dogs.

Study Design

Randomized block (dog); historical control.

Animals

Adult male Beagles (n = 10).

Methods

Two 2 × 2 cm2 wounds were surgically created bilaterally on the trunk of each dog. Each side was randomized to receive LLLT (laser, LAS) or standard‐of‐care management (control, CON), 3 times weekly for 32 days. The LLLT consisted of a dual diode laser (7.5 mW/diode) at 635 nm and total energy density of 1.125 J/cm2. Wound planimetry was performed on the caudal wounds, from which percent contraction and percent epithelialization were calculated. Histologic features were evaluated at 7 time points from cranial wound biopsies. Experimental data were also compared to wounds from a historical female control cohort (historical control, HCON).

Results

There was no difference between LAS and CON wounds for all parameters, including histology. The HCON wounds had significantly greater contraction and epithelialization compared to LAS and CON wounds. The LAS and CON wounds had significantly less inflammation than HCON wounds early in wound healing, but inflammation was significantly greater in LAS and CON wounds by day 21. Fibroblast infiltration and collagen deposition were significantly less in LAS and CON wounds than HCON wounds.

Conclusion

There are no apparent beneficial effects of LLLT on the healing of acute wounds in healthy dogs using this LLLT protocol. Gender may influence wound healing in intact dogs.
Modeling and Experimental Study of Solid–Liquid Two-Phase Pressure Drop in Horizontal Wellbores With Pipe Rotation
Authors: Sorgun Mehmet , Ulker Erman
Published: October 2015

Determining pressure loss for cuttings-liquid system is very complicated task since drillstring is usually rotating during drilling operations and cuttings are present inside wells. While pipe rotation is increasing the pressure loss of Newtonian fluids without cuttings in an eccentric annulus, a reduction in the pressure loss for cuttings-liquid system is observed due to the bed erosion. In this study, cuttings transport experiments for different flow rates, pipe rotation speeds, and rate of penetrations (ROPs) are conducted. Pressure loss within the test section and stationary and/or moving bed thickness are recorded. This study aims to predict frictional pressure loss for solid (cuttings)–liquid flow inside horizontal wells using computational fluid dynamics (CFD) and artificial neural networks (ANNs). For this purpose, numerous ANN structures and CFD models are developed and tested using experimental data. Among the ANN structures, TrainGdx–Tansig structure gave more accurate results. The results show that the ANN showed better performance than the CFD. However, both could be used to estimate solid–liquid two-phase pressure drop in horizontal wellbores with pipe rotation.
The Effective Modulus of Random Checkerboard Plates
Authors: Dimas Leon S. , Veneziano Daniele , Buehler Markus J.
Published: October 2015

We investigate the elastic effective modulus Eeff of two-dimensional checkerboard specimens in which square tiles are randomly assigned to one of two component phases. This is a model system for a wide class of multiphase polycrystalline materials such as granitic rocks and many ceramics. We study how the effective stiffness is affected by different characteristics of the specimen (size relative to the tiles, stiff fraction, and modulus contrast between the phases) and obtain analytical approximations to the probability distribution of Eeff as a function of these parameters. In particular, we examine the role of percolation of the soft and stiff phases, a phenomenon that is important in polycrystalline materials and composites with inclusions. In small specimens, we find that the onset of percolation causes significant discontinuities in the effective modulus, whereas in large specimens, the influence of percolation is smaller and gradual. The analysis is an extension of the elastic homogenization methodology of Dimas et al. (2015, “Random Bulk Properties of Heterogeneous Rectangular Blocks With Lognormal Young's Modulus: Effective Moduli,” ASME J. Appl. Mech., 82(1), p. 011003), which was devised for blocks with lognormal spatial variation of the modulus. Results are validated through Monte Carlo simulation. Compared with lognormal specimens with comparable first two moments, checkerboard plates have more variable effective modulus and are on average less compliant if there is prevalence of stiff tiles and more compliant if there is prevalence of soft tiles. These differences are linked to percolation.
Biased Information Passing Between Subsystems Over Time in Complex System Design
Authors: Austin-Breneman Jesse , Yu Bo Yang , Yang Maria C.
Published: October 2015

During the early stage design of large-scale engineering systems, design teams are challenged to balance a complex set of considerations. The established structured approaches for optimizing complex system designs offer strategies for achieving optimal solutions, but in practice suboptimal system-level results are often reached due to factors such as satisficing, ill-defined problems, or other project constraints. Twelve subsystem and system-level practitioners at a large aerospace organization were interviewed to understand the ways in which they integrate subsystems in their own work. Responses showed subsystem team members often presented conservative, worst-case scenarios to other subsystems when negotiating a tradeoff as a way of hedging against their own future needs. This practice of biased information passing, referred to informally by the practitioners as adding “margins,” is modeled in this paper with a series of optimization simulations. Three “bias” conditions were tested: no bias, a constant bias, and a bias which decreases with time. Results from the simulations show that biased information passing negatively affects both the number of iterations needed and the Pareto optimality of system-level solutions. Results are also compared to the interview responses and highlight several themes with respect to complex system design practice.
Comparison between polyethylene glycol and zwitterionic polymers as antifouling coatings on wearable devices for selective antigen capture from biological tissue
Authors: Robinson Kye J. , Coffey Jacob W. , Muller David A. , Young Paul R. , Kendall Mark A. F. , Thurecht Kristofer J. , Grøndahl Lisbeth , Corrie Simon R.
Published: October 2015

Selective capture of disease-related proteins in complex biological fluids and tissues is an important aim in developing sensitive protein biosensors for in vivo applications. Microprojection arrays are biomedical devices whose mechanical and chemical properties can be tuned to allow efficient penetration of skin, coupled with highly selective biomarker capture from the complex biological environment of skin tissue. Herein, the authors describe an improved surface modification strategy to produce amine-modified polycarbonate arrays, followed by the attachment of an antifouling poly(sulfobetaine-methacrylate) (pSBMA) polymer or a linear polyethylene glycol (PEG) polymer of comparative molecular weight and hydrodynamic radius. Using a “grafting to” approach, pSBMA and linear PEG coatings yielded comparative antifouling behavior in single protein solutions, diluted plasma, or when applied to mouse flank skin penetrating into the vascularized dermal tissue. Interestingly, the density of immobilized immunoglobulin G (IgG) or bovine serum albumin protein on pSBMA surfaces was significantly higher than that on the PEG surfaces, while the nonspecific adsorption was comparable for each protein. When incubated in buffer or plasma solutions containing dengue non-structural protein 1 (NS1), anti-NS1-IgG-coated pSBMA surfaces captured significantly more NS1 in comparison to PEG-coated devices. Similarly, when wearable microprojection arrays were applied to the skin of dengue-infected mice using the same coatings, the pSBMA-coated devices showed significantly higher capture efficiency (>2-fold increase in signal) than the PEG-coated substrates, which showed comparative signal when applied to naïve mice. In conclusion, zwitterionic pSBMA polymers (of equivalent hydrodynamic radii to PEG) allowed detection of dengue NS1 disease biomarker in a preclinical model of dengue infection, showing significantly higher signal-to-noise ratio in comparison to the PEG controls. The results of this study will be useful in the future development of a range of protein biosensors designed for use in vivo.
Resistive memory properties of an electrochemical SiO2-based device without an active electrode
Authors: Liu Chih-Yi , Chiang Kun-Chi , Lai Chun-Hung
Published: October 2015

A Ni (200 nm)/CuxO (7 nm)/SiO2 (20 nm)/W structure is fabricated in order to investigate its resistive memory properties. The resistance of the Ni/CuxO/SiO2/W structure can be reversibly switched between a high-resistance state and a low-resistance state (LRS) by applied voltages in different polarities. According to the switching behavior, the results of cyclic voltammetry, and the positive temperature coefficient of the LRS resistance, the switching mechanism is dominated by the electrochemical reaction with Cu conducting filaments. This Ni/CuxO/SiO2/W structure lacks an active electrode, but still has the characteristics of an electrochemical resistive memory. The CuxO layer provides Cu ions to form Cu conducting filaments during resistive switching. The Ni/CuxO/SiO2/W structure can also be operated in a vaporless environment, which overcomes the ambient issue for the traditional Cu/SiO2/W structure. The Ni/CuxO/SiO2/W structure exhibits reliable resistive switching and a lower ambient effect, and can be more flexibly integrated with complementary metal–oxide–semiconductor processes than the traditional Cu/SiO2/W structure.
Microwave ablation at 915 MHz vs 2.45 GHz: A theoretical and experimental investigation
Authors: Curto Sergio , Taj‐Eldin Mohammed , Fairchild Dillon , Prakash Punit
Published: October 2015

Purpose:

The relationship between microwave ablation system operating frequency and ablation performance is not currently well understood. The objective of this study was to comparatively assess the differences in microwave ablation at 915 MHz and 2.45 GHz.

Methods:

Analytical expressions for electromagnetic radiation from point sources were used to compare power deposition at the two frequencies of interest. A 3D electromagnetic‐thermal bioheat transfer solver was implemented with the finite element method to characterize power deposition and thermal ablation with asymmetrical insulated dipole antennas (single‐antenna and dual‐antenna synchronous arrays). Simulation results were validated against experiments in ex vivo tissue.

Results:

Theoretical, computational, and experimental results indicated greater power deposition and larger diameter ablation zones when using a single insulated microwave antenna at 2.45 GHz; experimentally, 32 ± 4.1 mm and 36.3 ± 1.0 mm for 5 and 10 min, respectively, at 2.45 GHz, compared to 24 ± 1.7 mm and 29.5 ± 0.6 mm at 915 MHz, with 30 W forward power at the antenna input port. In experiments, faster heating was observed at locations 5 mm (0.91 vs 0.49 °C/s) and 10 mm (0.28 vs 0.15 °C/s) from the antenna operating at 2.45 GHz. Larger ablation zones were observed with dual‐antenna arrays at 2.45 GHz; however, the differences were less pronounced than for single antennas.

Conclusions:

Single‐ and dual‐antenna arrays systems operating at 2.45 GHz yield larger ablation zone due to greater power deposition in proximity to the antenna, as well as greater role of thermal conduction.
Measuring neutron spectra in radiotherapy using the nested neutron spectrometer
Authors: Maglieri Robert , Licea Angel , Evans Michael , Seuntjens Jan , Kildea John
Published: October 2015

Purpose:

Out‐of‐field neutron doses resulting from photonuclear interactions in the head of a linear accelerator pose an iatrogenic risk to patients and an occupational risk to personnel during radiotherapy. To quantify neutron production, in‐room measurements have traditionally been carried out using Bonner sphere systems (BSS) with activation foils and TLDs. In this work, a recently developed active detector, the nested neutron spectrometer (NNS), was tested in radiotherapy bunkers.

Methods:

The NNS is designed for easy handling and is more practical than the traditional BSS. Operated in current‐mode, the problem of pulse pileup due to high dose‐rates is overcome by measuring current, similar to an ionization chamber. In a bunker housing a Varian Clinac 21EX, the performance of the NNS was evaluated in terms of reproducibility, linearity, and dose‐rate effects. Using a custom maximum‐likelihood expectation–maximization algorithm, measured neutron spectra at various locations inside the bunker were then compared to Monte Carlo simulations of an identical setup. In terms of dose, neutron ambient dose equivalents were calculated from the measured spectra and compared to bubble detector neutron dose equivalent measurements.

Results:

The NNS‐measured spectra for neutrons at various locations in a treatment room were found to be consistent with expectations for both relative shape and absolute magnitude. Neutron fluence‐rate decreased with distance from the source and the shape of the spectrum changed from a dominant fast neutron peak near the Linac head to a dominant thermal neutron peak in the moderating conditions of the maze. Monte Carlo data and NNS‐measured spectra agreed within 30% at all locations except in the maze where the deviation was a maximum of 40%. Neutron ambient dose equivalents calculated from the authors’ measured spectra were consistent (one standard deviation) with bubble detector measurements in the treatment room.

Conclusions:

The NNS may be used to reliably measure the neutron spectrum of a radiotherapy beam in less than 1 h, including setup and data unfolding. This work thus represents a new, fast, and practical method for neutron spectral measurements in radiotherapy.
Determination of lead ion removal from a flowing electrolyte in the presence of a magnetic field using Raman spectroscopy
Authors: Rodríguez Rogelio , Rangel Domingo , Vargas Susana , González Maykel , Malagon Karla , Quintanilla Francisco
Published: October 2015

Purpose:

The authors report on the development of a new, noninvasive method to efficiently remove metal ions in aqueous solution flowing in a tube and to quantify the concentrations of those ions. Such a technique could be used to remove toxic ions in the interiors of arteries and veins in patients intoxicated by the ingestion of metal ions.

Methods:

A magnetic field is applied to an aqueous electrolyte flowing in a specially designed rectangular cell in order to deflect the ion trajectories and concentrate them at one side of a cell. Once the ions are concentrated, they can be removed. Raman spectroscopy is used to promptly determine the concentration of the removed lead ions.

Results:

It is possible to increase, on one side of the cell, the ion concentration by more than 80% with respect to the average concentration; the removed ions were taken from this high concentration region. This approach is a rapid, efficient, and noninvasive method for the removal of ions in aqueous solution. Raman spectroscopy was found to be a suitable technique to determine the amount of removed ions.

Conclusions:

The results indicate that the ion concentration can be increased more than 80% in a region where they can be removed. The increment in the ion concentration produced by the deflection due to the magnetic field, together with the use of Raman spectroscopy, allows for a rapid analysis of the removed ions without any previous preparation. The proposed method is a potentially useful method for metal ion separation of interest in the medical physics field.
Multiple and single snapshot compressive beamforming
Authors: Gerstoft Peter , Xenaki Angeliki , Mecklenbräuker Christoph F.
Published: October 2015

For a sound field observed on a sensor array, compressive sensing (CS) reconstructs the direction of arrival (DOA) of multiple sources using a sparsity constraint. The DOA estimation is posed as an underdetermined problem by expressing the acoustic pressure at each sensor as a phase-lagged superposition of source amplitudes at all hypothetical DOAs. Regularizing with an ℓ1-norm constraint renders the problem solvable with convex optimization, and promoting sparsity gives high-resolution DOA maps. Here the sparse source distribution is derived using maximum a posteriori estimates for both single and multiple snapshots. CS does not require inversion of the data covariance matrix and thus works well even for a single snapshot where it gives higher resolution than conventional beamforming. For multiple snapshots, CS outperforms conventional high-resolution methods even with coherent arrivals and at low signal-to-noise ratio. The superior resolution of CS is demonstrated with vertical array data from the SWellEx96 experiment for coherent multi-paths.
Nonadditivity of nanoparticle interactions
Authors: Silvera Batista Carlos A. , Larson Ronald G. , Kotov Nicholas A.
Published: October 2015

Solutions for nanoparticle solutions

Nanoparticle interactions in solution affect their binding to biomolecules, their electronic properties, and their packing into larger crystals. However, the theories that describe larger colloidal particles fail for nanoparticles, because the interactions do not add together linearly. Nanoparticles also have complex shapes and are closer in size to the solvent molecules. Silvera Batista
et al.
review approaches that can treat the nonadditive nature of nanoparticle interactions, resulting in a more complete understanding of nanoparticles in solution.

Science
, this issue p.
10.1126/science.1242477
Neglected tropical diseases get the limelight in Stockholm
Authors: Stokstad Erik , Vogel Gretchen
Published: October 2015

Medicine award honors pioneers who developed powerful drugs against malaria and roundworms.
How crop-killing witchweed senses its victims
Authors: Pennisi Elizabeth
Published: October 2015

Pinning down molecules key to finding a host plant paves the way for new controls on the parasite.
Hostile shores
Authors: Larson Christina
Published: October 2015

Migratory bird populations in Asia are crashing as Yellow Sea habitat dwindles.
Chiral solitons in a coupled double Peierls chain
Authors: Cheon Sangmo , Kim Tae-Hwan , Lee Sung-Hoon , Yeom Han Woong
Published: October 2015

Handedness at the edge of a line

Topological insulators are characterized by conducting boundary states. For those existing as two-dimensional (2D) materials, the boundaries are lines, the edge currents are 1D, and their two spin components flow in opposite directions. To address whether this handedness also applies to the edge states of 1D topological systems, Cheon
et al.
deposited indium atoms on the surface of silicon, where the atoms formed wires consisting of double zigzag chains. The chains underwent distortions that caused topological edge states called solitons to appear under certain conditions. The solitons came in three flavors, two of which had a definite handedness.

Science
, this issue p.
182
Comment on “Statistical binning enables an accurate coalescent-based estimation of the avian tree”
Authors: Liu Liang , Edwards Scott V.
Published: October 2015

Mirarab
et al
. (Research Article, 12 December 2014, p. 1250463) introduced statistical binning to improve the signal in phylogenetic methods using the multispecies coalescent model. We show that all forms of binning—naïve, statistical, and weighted statistical—display poor performance and are statistically inconsistent in large regions of parameter space, unlike unbinned sequence data used with species tree methods.
Response to Comment on “Statistical binning enables an accurate coalescent-based estimation of the avian tree”
Authors: Mirarab Siavash , Bayzid Md. Shamsuzzoha , Boussau Bastien , Warnow Tandy
Published: October 2015

Liu and Edwards argue against the use of weighted statistical binning within a species tree estimation pipeline. However, we show that their mathematical argument does not apply to weighted statistical binning. Furthermore, their simulation study does not follow the recommended statistical binning protocol and has data of unknown origin that bias the results against weighted statistical binning.
Finding optimal surface sites on heterogeneous catalysts by counting nearest neighbors
Authors: Calle-Vallejo Federico , Tymoczko Jakub , Colic Viktor , Vu Quang Huy , Pohl Marcus D. , Morgenstern Karina , Loffreda David , Sautet Philippe , Schuhmann Wolfgang , Bandarenka Aliaksandr S.
Published: October 2015

Accounting for surface coordination

The exploration of heterogeneous catalysts using first-principles calculations can be daunting because the large number of atoms and possible surface geometries. Calle-Vallejo
et al.
describe a simpler metric for assessing optimal reactivity: a weighted average of surface coordination that includes second-nearest neighbors (see the Perspective by Stephens
et al.
). The calculations identified three approaches for introducing cavity sites into the platinum(111) surface to improve its performance for the oxygen reduction reaction used in fuel cells.

Science
, this issue p.
185
, see also p.
164
Visualization of cellulose synthases in
Arabidopsis
secondary cell walls
Authors: Watanabe Y. , Meents M. J. , McDonnell L. M. , Barkwill S. , Sampathkumar A. , Cartwright H. N. , Demura T. , Ehrhardt D. W. , Samuels A.L. , Mansfield S. D.
Published: October 2015

Secondary cell walls built with speed

Plant cell walls provide the cellulose that is integral for wood, cotton fiber, and many biofuels. Cellulose is synthesized outside the cell membrane by cellulose synthase enzymes. Much of the secondary cell wall, responsible for the sturdiness of wood, is formed by xylem cells embedded in the core of the plant. Watanabe
et al.
leveraged ectopic expression to bring xylem-style cellulose synthase activity to the epidermal surface of the plant (see the Perspective by Schneider and Persson). Combining this improved accessibility with fluorescent tagging showed that secondary cell walls are built faster than primary cell walls, perhaps due to increased velocity and density of cellulose synthase complexes.

Science
, this issue p.
198
, see also p.
156
Structure-function analysis identifies highly sensitive strigolactone receptors in
Striga
Authors: Toh Shigeo , Holbrook-Smith Duncan , Stogios Peter J. , Onopriyenko Olena , Lumba Shelley , Tsuchiya Yuichiro , Savchenko Alexei , McCourt Peter
Published: October 2015

Striga
uses a hypersensitive receptor

The strigolactone hormones govern plant growth and development. A nasty parasitic weed,
Striga
, senses traces of these hormones to identify its targets. After functionally characterizing several strigolactone receptors from
Striga
, Toh
et al.
solved the crystal structure of one that is especially sensitive. The structure shows an unexpectedly large ligand-binding pocket, which may explain how
Striga
manages to sense picomolar concentrations of the range of strigolactones.

Science
, this issue p.
203
A bright future
Harness the Sun America's Quest for a Solar-Powered Future
Philip Warburg
Beacon Press, 2015. 251 pp.
Authors: Lovins Amory B.
Published: October 2015

The rise of solar energy and the path ahead for America's renewable energy sector
Another brick in the wall
Authors: Schneider Rene , Persson Staffan
Published: October 2015

An inducible secondary wall system reveals how most plant biomass is synthesized

[Also see Report by

Watanabe
et al.

]
The importance of being together
Authors: Stephens Ifan E. L. , Elias Joseph S. , Shao-Horn Yang
Published: October 2015

Controlling the coordination of platinum boosts catalytic reaction rates

[Also see Reports by

Calle-Vallejo
et al.

and

Ding
et al.

]
Vaccination with a Porcine Reproductive and Respiratory Syndrome (PRRS) Modified Live Virus Vaccine Followed by Challenge with PRRS Virus and Porcine Circovirus Type 2 (PCV2) Protects against PRRS but Enhances PCV2 Replication and Pathogenesis Compared to Results for Nonvaccinated Cochallenged Controls
Authors: Niederwerder Megan C. , Bawa Bhupinder , Serão Nick V. L. , Trible Benjamin R. , Kerrigan Maureen A. , Lunney Joan K. , Dekkers Jack C. M. , Rowland Raymond R. R.
Published: October 2015

Coinfections involving porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) contribute to a group of disease syndromes known as porcine circovirus-associated disease (PCVAD). Presumably, PRRSV infection enhances PCV2 replication as a result of modulation of host immunity. The purpose of this study was to evaluate PCV2 replication and pathogenesis in pigs vaccinated with a PRRS modified live virus (MLV) vaccine and subsequently challenged with a combination of PRRSV and PCV2. During the early postchallenge period, the number of pigs with PRRSV-associated clinical signs was decreased, and average daily gain (ADG) was increased, in the vaccinated group, demonstrating the protective effect of PRRS vaccination. However, during the later postchallenge period, more pigs in the vaccinated group showed increased PCV2 viremia, decreased ADG, increased PCVAD clinical signs, and increased mortality. In this disease model, the early benefits of PRRSV vaccination were outweighed by the later amplification of PCVAD.
Evaluation of a New Immunochromatographic Test Using Recombinant Antigen B8/1 for Diagnosis of Cystic Echinococcosis
Authors: Santivañez Saul J. , Rodriguez Mary L. , Rodriguez Silvia , Sako Yashuito , Nkouawa Agathe , Kobayashi Yukuharu , Sotomayor Alfredo L. , Peralta Julio E. , Valcarcel Maria , Gonzalez Armando E. , Garcia Hector H. , Ito Akira
Published: October 2015

Diagnosis of cystic echinococcosis (CE) is based on the identification of the cyst(s) by imaging, using immunodiagnostic tests mainly as complementary tools in clinical settings. Among the antigens used for immunodiagnosis, previous studies described a good performance of the recombinant antigen B8/1 (rAgB) in an enzyme-linked immunosorbent assay (ELISA) format; however, in remote parts of areas where the disease is endemic, the implementation of an ELISA is difficult, so a more simple, rapid, and reliable method such as the immunochromatographic test (ICT) is required. In this study, using a set of 50 serum samples from patients with surgically confirmed CE, we compared the performance of an ICT and that of an ELISA using the rAgB. The overall sensitivities of ICT and ELISA were not statistically different (78% versus 72%;
P
= 0.36). The overall agreement between both tests was moderate (κ = 0.41;
P
< 0.01). Concordance between ICT and ELISA was substantial or almost perfect for patients with liver involvement (κ = 0.65;
P
< 0.001) and patients with more than one hydatid cyst (κ = 0.82;
P
< 0.001), respectively. Moreover, specificity analysis using a total of 88 serum samples from healthy individuals (
n
= 20) and patients (
n
= 68) with other parasitic infections revealed that ICT had a specificity of 89.8%. ICT and ELISA had similar performance for the detection of specific antibodies to
E. granulosus
, and ICT had a high specificity, opening the possibility of using ICT as a screening tool in rural settings.
Crawling with Virus: Translational Insights from a Neonatal Mouse Model on the Pathogenesis of Respiratory Syncytial Virus in Infants
Authors: You Dahui , Saravia Jordy , Siefker David , Shrestha Bishwas , Cormier Stephania A.
Published: October 2015

The infant immune response to respiratory syncytial virus (RSV) remains incompletely understood. Here we review the use of a neonatal mouse model of RSV infection to mimic severe infection in human infants. We describe numerous age-specific responses, organized by cell type, observed in RSV-infected neonatal mice and draw comparisons (when possible) to human infants.
Mismatches in the Influenza A Virus RNA Panhandle Prevent Retinoic Acid-Inducible Gene I (RIG-I) Sensing by Impairing RNA/RIG-I Complex Formation
Authors: Anchisi Stéphanie , Guerra Jessica , Mottet-Osman Geneviève , Garcin Dominique
Published: October 2015

Influenza virus RNA (vRNA) promoter panhandle structures are believed to be sensed by retinoic acid-inducible gene I (RIG-I). The occurrence of mismatches in this double-stranded RNA structure raises questions about their effect on innate sensing. Our results suggest that mismatches in vRNA promoters decrease binding to RIG-I
in vivo
, affecting RNA/RIG-I complex formation and preventing RIG-I activation. These results can be inferred to apply to other viruses and suggest that mismatches may represent a general viral strategy to escape RIG-I sensing.
Cocirculation of Two
env
Molecular Variants, of Possible Recombinant Origin, in Gorilla and Chimpanzee Simian Foamy Virus Strains from Central Africa
Authors: Richard Léa , Rua Réjane , Betsem Edouard , Mouinga-Ondémé Augustin , Kazanji Mirdad , Leroy Eric , Njouom Richard , Buseyne Florence , Afonso Philippe V. , Gessain Antoine
Published: October 2015

Simian foamy virus (SFV) is a ubiquitous retrovirus in nonhuman primates (NHPs) that can be transmitted to humans, mostly through severe bites. In the past few years, our laboratory has identified more than 50 hunters from central Africa infected with zoonotic SFVs. Analysis of the complete sequences of five SFVs obtained from these individuals revealed that
env
was the most variable gene. Furthermore, recombinant SFV strains, some of which involve sequences in the
env
gene, were recently identified. Here, we investigated the variability of the
env
genes of zoonotic SFV strains and searched for possible recombinants. We sequenced the complete
env
gene or its surface glycoprotein region (SU) from DNA amplified from the blood of (i) a series of 40 individuals from Cameroon or Gabon infected with a gorilla or chimpanzee foamy virus (FV) strain and (ii) 1 gorilla and 3 infected chimpanzees living in the same areas as these hunters. Phylogenetic analyses revealed the existence of two
env
variants among both the gorilla and chimpanzee FV strains that were present in zoonotic and NHP strains. These variants differ greatly (>30% variability) in a 753-bp-long region located in the receptor-binding domain of SU, whereas the rest of the gene is very conserved. Although the organizations of the Env protein sequences are similar, the potential glycosylation patterns differ between variants. Analysis of recombination suggests that the variants emerged through recombination between different strains, although all parental strains could not be identified.

IMPORTANCE
SFV infection in humans is a great example of a zoonotic retroviral infection that has not spread among human populations, in contrast to human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). Recombination was a major mechanism leading to the emergence of HIV. Here, we show that two SFV molecular envelope gene variants circulate among ape populations in Central Africa and that both can be transmitted to humans. These variants differ greatly in the SU region that corresponds to the part of the Env protein in contact with the environment. These variants may have emerged through recombination between SFV strains infecting different NHP species.
Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease
Authors: Tao Xinrong , Garron Tania , Agrawal Anurodh Shankar , Algaissi Abdullah , Peng Bi-Hung , Wakamiya Maki , Chan Teh-Sheng , Lu Lu , Du Lanying , Jiang Shibo , Couch Robert B. , Tseng Chien-Te K.
Published: October 2015

Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID
50
) and lethal dose (LD
50
) of virus were estimated to be <1 and 10 TCID
50
of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID
50
/LD
50
determinations, and all were fully immune to challenge with 100 LD
50
of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD
50
of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 10
5
LD
50
of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research.

IMPORTANCE
Fully characterized animal models are essential for studying pathogenesis and for preclinical screening of vaccines and drugs against MERS-CoV infection and disease. When given a high dose of MERS-CoV, our transgenic mice expressing hCD26/DPP4 viral receptor uniformly succumbed to death within 6 days, making it difficult to evaluate host responses to infection and disease. We further characterized this model by determining both the ID
50
and the LD
50
of MERS-CoV in order to establish both an infection model and a lethal model for MERS and followed this by investigating the antibody responses and immunity of the mice that survived MERS-CoV infection. Using the estimated LD
50
and ID
50
data, we dissected the kinetics of viral tissue distribution and pathology in mice challenged with 10 LD
50
of virus and utilized the model for preclinical evaluation of a vaccine and drug for treatment of MERS-CoV infection. This further-characterized transgenic mouse model will be useful for advancing MERS research.
Oligomerization Requirements for MX2-Mediated Suppression of HIV-1 Infection
Authors: Dicks Matthew D. J. , Goujon Caroline , Pollpeter Darja , Betancor Gilberto , Apolonia Luis , Bergeron Julien R. C. , Malim Michael H.
Published: October 2015

Human myxovirus resistance 2 (MX2/MXB) is an interferon-stimulated gene (ISG) and was recently identified as a late postentry suppressor of human immunodeficiency virus type 1 (HIV-1) infection, inhibiting the nuclear accumulation of viral cDNAs. Although the HIV-1 capsid (CA) protein is believed to be the viral determinant of MX2-mediated inhibition, the precise mechanism of antiviral action remains unclear. The MX family of dynamin-like GTPases also includes MX1/MXA, a well-studied inhibitor of a range of RNA and DNA viruses, including influenza A virus (FLUAV) and hepatitis B virus but not retroviruses. MX1 and MX2 are closely related and share similar domain architectures and structures. However, MX2 possesses an extended N terminus that is essential for antiviral function and confers anti-HIV-1 activity on MX1 [MX1(N
MX2
)]. Higher-order oligomerization is required for the antiviral activity of MX1 against FLUAV, with current models proposing that MX1 forms ring structures that constrict around viral nucleoprotein complexes. Here, we performed structure-function studies to investigate the requirements for oligomerization of both MX2 and chimeric MX1(N
MX2
) for the inhibition of HIV-1 infection. The oligomerization state of mutated proteins with amino acid substitutions at multiple putative oligomerization interfaces was assessed using a combination of covalent cross-linking and coimmunoprecipitation. We show that while monomeric MX2 and MX1(N
MX2
) mutants are not antiviral, higher-order oligomerization does not appear to be required for full antiviral activity of either protein. We propose that lower-order oligomerization of MX2 is sufficient for the effective inhibition of HIV-1.

IMPORTANCE
Interferon plays an important role in the control of virus replication during acute infection
in vivo
. Recently, cultured cell experiments identified human MX2 as a key effector in the interferon-mediated postentry block to HIV-1 infection. MX2 is a member of a family of large dynamin-like GTPases that includes MX1/MXA, a closely related interferon-inducible inhibitor of several viruses, including FLUAV, but not HIV-1. MX GTPases form higher-order oligomeric structures, and the oligomerization of MX1 is required for inhibitory activity against many of its viral targets. Through structure-function studies, we report that monomeric mutants of MX2 do not inhibit HIV-1. However, in contrast to MX1, oligomerization beyond dimer assembly does not seem to be required for the antiviral activity of MX2, implying that fundamental differences exist between the antiviral mechanisms employed by these closely related proteins.