bluuebunny/crossref_metadata_2025 huggingface dataset:
HISTONE DEACETYLASE 9 represses seedling traits in Arabidopsis thaliana dry seeds
Authors: van Zanten Martijn , Zöll Christian , Wang Zhi , Philipp Christina , Carles Annaick , Li Yong , Kornet Noortje G. , Liu Yongxiu , Soppe Wim J. J.
Published: August 2014

Plant life is characterized by major phase changes. We studied the role of histone deacetylase (HDAC) activity in the transition from seed to seedling in Arabidopsis. Pharmacological inhibition of HDAC stimulated germination of freshly harvested seeds. Subsequent analysis revealed that histone deacetylase 9 (hda9) mutant alleles displayed reduced seed dormancy and faster germination than wild‐type plants. Transcriptome meta‐analysis comparisons between the hda9 dry seed transcriptome and published datasets demonstrated that transcripts of genes that are induced during imbibition in wild‐type prematurely accumulated in hda9‐1 dry seeds. This included several genes associated with photosynthesis and photoautotrophic growth such as RuBisCO and RuBisCO activase (RCA). Chromatin immunoprecipitation experiments demonstrated enhanced histone acetylation levels at their loci in young hda9‐1 seedlings. Our observations suggest that HDA9 negatively influences germination and is involved in the suppression of seedling traits in dry seeds, probably by transcriptional repression via histone deacetylation. Accordingly, HDA9 transcript is abundant in dry seeds and becomes reduced during imbibition in wild‐type seeds. The proposed function of HDA9 is opposite to that of its homologous genes HDA6 and HDA19, which have been reported to repress embryonic properties in germinated seedlings.
Thrombocytopenia in late preterm and term neonates after perinatal asphyxia
Authors: Christensen Robert D. , Baer Vickie L. , Yaish Hassan M.
Published: August 2014

Background

A recent NHLBI conference concluded that platelet (PLT) transfusions of neonates must become more evidence based. One neonatal disorder for which transfusions are given is a poorly defined entity, the “thrombocytopenia of perinatal asphyxia.” To expand the evidence base for this entity, we performed a multicentered, retrospective analysis of neonates with perinatal asphyxia.

Study Design and Methods

We analyzed records of term and late preterm neonates with perinatal asphyxia defined by a cord blood pH of not more than 6.99 and/or base deficit of at least 16 mmol/L. From these we identified neonates with at least two PLT counts of fewer than 150 × 109/L in the first week of life and described the severity, nadir, and duration of the thrombocytopenia.

Results

Thrombocytopenia occurred in 31% (117/375) of neonates with asphyxia versus 5% of matched nonasphyxiated controls admitted to a neonatal intensive care unit (p < 0.0001). Twenty‐one of the 117 asphyxiated neonates were excluded from the remaining analysis due to disseminated intravascular coagulation or extracorporeal membrane oxygenation. Nadir PLT counts of the remaining 96 were on Day 3 (75 × 109/L; 90% confidence interval, 35.7 × 109‐128.6 × 109/L) and normalized by Days 19 to 21. PLT counts after asphyxia roughly correlated inversely with elevated nucleated red blood cell count (NRBC) counts at birth. Thirty of the 96 received at least one PLT transfusion, all given prophylactically, none for bleeding.

Conclusions

We maintain that the thrombocytopenia of perinatal asphyxia is an authentic entity. Its association with elevated NRBC counts suggests that hypoxia is involved in the pathogenesis. Because PLT counts are only moderately low, the condition is transient, and bleeding problems seem rare, we speculate that PLT transfusions should not be needed for most neonates with this condition.
Linear algebra over and related rings
Authors: Caruso Xavier , Lubicz David
Published: August 2014

Let $\mathfrak{R}$ be a complete discrete valuation ring, $S=\mathfrak{R}[[u]]$ and $d$ a positive integer. The aim of this paper is to explain how to efficiently compute usual operations such as sum and intersection of sub-$S$-modules of $S^d$. As $S$ is not principal, it is not possible to have a uniform bound on the number of generators of the modules resulting from these operations. We explain how to mitigate this problem, following an idea of Iwasawa, by computing an approximation of the result of these operations up to a quasi-isomorphism. In the course of the analysis of the $p$-adic and $u$-adic precisions of the computations, we have to introduce more general coefficient rings that may be interesting for their own sake. Being able to perform linear algebra operations modulo quasi-isomorphism with $S$-modules has applications in Iwasawa theory and $p$-adic Hodge theory. It is used in particular in Caruso and Lubicz (Preprint, 2013, arXiv:1309.4194) to compute the semi-simplified modulo $p$ of a semi-stable representation.
Passive Noise Reduction for a Contrarotating Fan
Authors: Wang Chen , Huang Lixi
Published: August 2014

There has been renewed interest in the contrarotating (CR) fan configuration in aviation and other applications where size and weight are important design factors. Contra-rotation recovers swirl energy compared with the single-rotor design, but this advantage is not fully harnessed due to, perhaps, the issue of noise. This study explores passive noise reduction for a small, axial-flow, CR fan with perforated trailing-edge for the upstream rotor and perforated leading-edge for the downstream rotor. The fan is designed with simple velocity triangle analyses, which are checked by 3D flow computations. The aerodynamic consequence and the acoustic benefit of such perforated blading are investigated experimentally. The results show that there is a reduction of total pressure compared with the baseline CR fan at the same rotating speeds, but this is easily compensated for by slightly raising the rotating speeds. A reduction of 6–7 dB in overall noise is achieved for the same aerodynamic output, although there is a moderate noise increase in the high frequency range of 12.5–15.0 kHz due to blade perforations. The effect of inter-rotor separation distance is also investigated for the baseline design. A clear critical distance exists below which the increased spacing shows clear acoustic benefits.
Influence of the Duration of Transfer From the Furnace to the Press During the Hot Stamping Process
Authors: Blaise Alexandre , Bourouga Brahim , Dessain Christine
Published: August 2014

During the hot stamping process a blank is first heated up 900 °C for 6 min 30 s. Then, the blank is transferred to the press where it is hot stamped. During the transfer, the blank is slowly cooled down by convection and radiation with the ambient air and metallurgical transformations can occur and modify the mechanical properties after hot stamping. Using samples with welded thermocouples, a method is presented to estimate the kinetic of the metallurgical transformations. The results are compared with the metallurgical analysis of samples that are quenched in the water after different transfer times. The influence of the thickness of the blank is also investigated. It is highlighted that using different thicknesses leads to different cooling rates and different resulting microstructures. The influence of the transfer time on the mechanical properties after hot stamping is highlighted with hardness measurements and tensile tests. Finally, a coupled heat transfer/metallurgical model is built to simulate the kinetic of the transformations and a diagram can be plotted that presents the evolution of the metallurgy as a function of the thickness and the transfer time. These results show the high importance of the transfer time from the furnace to the press and a tool is proposed to help the engineers to define a process window.
Optimal Transient Control Trajectories in Diesel–Electric Systems—Part I: Modeling, Problem Formulation, and Engine Properties
Authors: Sivertsson Martin , Eriksson Lars
Published: August 2014

A nonlinear four state-three input mean value engine model (MVEM), incorporating the important turbocharger dynamics, is used to study optimal control of a diesel–electric powertrain during transients. The optimization is conducted for the two criteria, minimum time and fuel, where both engine speed and engine power are considered free variables in the optimization. First, steps from idle to a target power are studied and for steps to higher powers the controls for both criteria follow a similar structure, dictated by the maximum torque line and the smoke-limiter. The end operating point, and how it is approached is, however, different. Then, the power transients are extended to driving missions, defined as, that a certain power has to be met as well as a certain energy has to be produced. This is done both with fixed output profiles and with the output power being a free variable. The time optimal control follows the fixed output profile even when the output power is free. These solutions are found to be almost fuel optimal despite being substantially faster than the minimum fuel solution with variable output power. The discussed control strategies are also seen to hold for sequences of power and energy steps.
Conceptual Design and Analysis of Hydrocarbon-Based Solar Thermal Power and Ejector Cooling Systems in Hot Climates
Authors: Zhang TieJun , Mohamed Saleh
Published: August 2014

A combined thermal power and ejector refrigeration cooling cycle is proposed in this paper to harness low-grade solar energy. It explores the possibility of utilizing abundant and low-cost hydrocarbon as the working fluid. Hydrocarbon fluid has been identified as a promising alternative to existing high global-warming-potential (GWP) refrigerants (i.e., HFCs) in next-generation cooling and organic thermal power systems. Several typical alternative refrigerants are evaluated by considering their fundamental thermophysical properties: absolute pressure level, volumetric cooling capacity, surface tension, saturated liquid/vapor density ratio, and kinematic viscosity. Comparing with R1234yf, R1234ze, and R744 (CO2), hydrocarbon refrigerants, such as R290 (propane) and R601 (pentane), do have inherent advantages for either cooling or power generation purposes in hot climates. Fundamental phase stability and transition issues have been considered in designing hydrocarbon ejectors for combined power and cooling cycles operating at high ambient temperature. Thermodynamic energy and exergy analysis has indicated that the proposed stand-alone solar thermal system offers an effective way to sustainable energy production in hot and dry climates.
The Effect of a Thermotropic Material on the Optical Efficiency and Stagnation Temperature of a Polymer Flat Plate Solar Collector
Authors: Gladen Adam C. , Davidson Jane H. , Mantell Susan C.
Published: August 2014

Solar hot water and space heating systems constructed of commodity polymers have the potential to reduce the initial cost of solar thermal systems. However, a polymer absorber must be prevented from exceeding its maximum service temperature during stagnation. Here, the addition of a thermotropic material to the surface of the absorber is considered. The thermotropic layer provides passive overheat protection by switching from high transmittance during normal operation to high reflectance if the temperature of the absorber becomes too high. A one dimensional model of a glazed, flat-plate collector with a polymer absorber and thermotropic material is used to determine the effects of the optical properties of the thermotropic material on the optical efficiency and the stagnation temperature of a collector. A key result is identification of the reflectance in the translucent state required to provide overheat protection for potential polymer absorber materials. For example, a thermotropic material in its translucent state should have a solar-weighted reflectance greater than or equal to 52% to protect a polypropylene absorber which has a maximum service temperature of 115 °C.
Natural Convection From Interrupted Vertical Walls
Authors: Ahmadi Mehran , Mostafavi Golnoosh , Bahrami Majid
Published: August 2014

Steady-state external natural convection heat transfer from interrupted rectangular vertical walls is investigated. A systematic numerical, experimental, and analytical study is conducted on the effect of adding interruptions to a vertical plate. Comsol multiphysics is used to develop a two-dimensional numerical model for investigation of fin interruption effects on natural convection. A custom-designed testbed is built and six interrupted wall samples are machined from aluminum. An effective length is introduced for calculating the natural convection heat transfer from interrupted vertical walls. Performing an asymptotic analysis and using a blending technique, a new compact relationship is proposed for the Nusselt number. Our results show that adding interruptions to a vertical wall can enhance heat transfer rate up to 16% and reduce the weight of the fins, which in turn, lead to lower manufacturing and material costs.
Numerical Investigations on the Leakage and Rotordynamic Characteristics of Pocket Damper Seals—Part I: Effects of Pressure Ratio, Rotational Speed, and Inlet Preswirl
Authors: Li Zhigang , Li Jun , Feng Zhenping
Published: August 2014

Effects of pressure ratio, rotational speed and inlet preswirl on the leakage and rotordynamic characteristics of a eight-bladed fully partitioned pocket damper seal (FPDS) were numerically investigated using proposed three-dimensional (3D) transient computational fluid dynamics (CFD) methods based on the multifrequency elliptical whirling orbit model. The accuracy and availability of the multifrequency elliptical whirling orbit model and the transient CFD numerical methods were demonstrated with the experimental data of frequency-dependent rotordynamic coefficients of the FPDS at two rotational speeds with high preswirl conditions. The frequency-dependent rotordynamic coefficients of the FPDS at three pressure ratios (three inlet pressures and three outlet pressures), three rotational speeds, three inlet preswirls were computed. The numerical results show that changes in outlet pressure have only weak effects on most rotordynamic coefficients. The direct damping and effective damping slightly increase in magnitude with decreasing outlet pressure at the frequency range of 20–200 Hz. The effect of inlet pressure is most prominent, and increasing inlet pressure for the FPDS results in a significant increase in the magnitudes of all rotordynamic coefficients. The magnitudes of the seal response force and effective damping are proportional to pressure drop through the seal. Increasing rotational speed and increasing inlet preswirl velocity both result in a significant decrease in the effective damping term due to the obvious increase in the magnitude of the destabilizing cross-coupling stiffness with increasing rotational speed or increasing preswirl velocity. The crossover frequency of effective damping significantly increases and the peak magnitude of effective damping decreases with increasing rotational speed or increasing preswirl velocity. The destabilizing cross-coupling stiffness is mainly caused by the circumferential swirl velocity generating from high rotational speed and inlet preswirl. Reducing swirl velocity (such as swirl brake) can greatly enhance the stabilizing capacity of the FPDS.
Numerical Investigations on the Leakage and Rotordynamic Characteristics of Pocket Damper Seals—Part II: Effects of Partition Wall Type, Partition Wall Number, and Cavity Depth
Authors: Li Zhigang , Li Jun , Feng Zhenping
Published: August 2014

Effects of partition wall type, partition wall number and cavity depth on the leakage and rotordynamic characteristics of the pocket damper seal (PDS) were numerically investigated using a presented 3D transient computational fluid dynamics (CFD) method based on the multifrequency elliptical whirling orbit model. The accuracy and availability of this transient CFD method and the multifrequency elliptical whirling orbit model were demonstrated with the experimental data of the experimental eight-bladed fully partitioned pocket damper seal (FPDS). The leakage flow rates and frequency-dependent rotordynamic coefficients of PDS were computed for two types of partition wall (namely conventional PDS and fully partitioned PDS), four partition wall numbers including the labyrinth seal (no partition wall) and six cavity depths including the plain smooth seal (zero cavity depth) at operational conditions with or without inlet preswirl and 15,000 rpm rotational speed. The numerical results show that the FPDS has the similar leakage performance and more superior stability capacity than the conventional PDS. The FPDS possesses slightly larger leakage flow rate (∼2.6–4.0% larger) compared to the labyrinth seal. Eight is a preferable value for the partition wall number to gain the best leakage performance of the FPDS with the least manufacturing cost. The FPDS possesses significantly larger stiffness and damping than the labyrinth seal. Increasing partition wall number results in a significant increase in the direct stiffness but limited desirable effect on the effective damping. The FPDS possesses the lowest leakage flow rate when the cavity depth is about 2.0 mm. Compared to the plain smooth seal, the FPDS possesses larger positive direct stiffness and significantly less direct damping and effective damping. Increasing cavity depth results in a significant decrease in the stabilizing direct damping and the magnitude of the destabilizing cross-coupling stiffness. H= 3.175 mm is a preferable value of the cavity depth for which the effective damping of the FPDS is largest, especially for the concerned frequencies (80–120 Hz) where most multistage high-pressure centrifugal compressors have stability problem.
Sound Absorption Optimization of Graded Semi-Open Cellular Metals by Adopting the Genetic Algorithm Method
Authors: Meng H. , Xin F. X. , Lu T. J.
Published: August 2014

Built upon the acoustic impedance of circular apertures and cylindrical cavities as well as the principle of electroacoustic analogy, an impedance model is developed to investigate theoretically the sound absorption properties of graded (multilayered) cellular metals having semi-open cells. For validation, the model predictions are compared with existing experimental results, with good agreement achieved. The results show that the distribution of graded geometrical parameters in the semi-open cellular metal, including porosity, pore size, and degree of pore opening (DPO), affects significantly its sound absorbing performance. A strategy by virtue of the genetic algorithm (GA) method is subsequently developed to optimize the sound absorption coefficient of the graded semi-open cellular metal. The objective functions and geometric constraint conditions are given in terms of the key geometrical parameters as design variables. Optimal design is conducted to seek for optimal distribution of the geometrical parameters in graded semi-open cellular metals.
Using computer‐extracted image features for modeling of error‐making patterns in detection of mammographic masses among radiology residents
Authors: Zhang Jing , Lo Joseph Y. , Kuzmiak Cherie M. , Ghate Sujata V. , Yoon Sora C. , Mazurowski Maciej A.
Published: August 2014

Purpose:

Mammography is the most widely accepted and utilized screening modality for early breast cancer detection. Providing high quality mammography education to radiology trainees is essential, since excellent interpretation skills are needed to ensure the highest benefit of screening mammography for patients. The authors have previously proposed a computer‐aided education system based on trainee models. Those models relate human‐assessed image characteristics to trainee error. In this study, the authors propose to build trainee models that utilize features automatically extracted from images using computer vision algorithms to predict likelihood of missing each mass by the trainee. This computer vision‐based approach to trainee modeling will allow for automatically searching large databases of mammograms in order to identify challenging cases for each trainee.

Methods:

The authors’ algorithm for predicting the likelihood of missing a mass consists of three steps. First, a mammogram is segmented into air, pectoral muscle, fatty tissue, dense tissue, and mass using automated segmentation algorithms. Second, 43 features are extracted using computer vision algorithms for each abnormality identified by experts. Third, error‐making models (classifiers) are applied to predict the likelihood of trainees missing the abnormality based on the extracted features. The models are developed individually for each trainee using his/her previous reading data. The authors evaluated the predictive performance of the proposed algorithm using data from a reader study in which 10 subjects (7 residents and 3 novices) and 3 experts read 100 mammographic cases. Receiver operating characteristic (ROC) methodology was applied for the evaluation.

Results:

The average area under the ROC curve (AUC) of the error‐making models for the task of predicting which masses will be detected and which will be missed was 0.607 (95% CI,0.564‐0.650). This value was statistically significantly different from 0.5 (p < 0.0001). For the 7 residents only, the AUC performance of the models was 0.590 (95% CI,0.537‐0.642) and was also significantly higher than 0.5 (p = 0.0009). Therefore, generally the authors’ models were able to predict which masses were detected and which were missed better than chance.

Conclusions:

The authors proposed an algorithm that was able to predict which masses will be detected and which will be missed by each individual trainee. This confirms existence of error‐making patterns in the detection of masses among radiology trainees. Furthermore, the proposed methodology will allow for the optimized selection of difficult cases for the trainees in an automatic and efficient manner.
Physical Demands of Match Play in Successful and Less-Successful Elite Rugby League Teams
Authors: Hulin Billy T. , Gabbett Tim J. , Kearney Simon , Corvo Alex
Published: August 2014

Purpose:

To quantify activity profiles in approximately 5-min periods to determine if the intensity of rugby league match play changes after the most intense period of play and to determine if the intensity of activity during predefined periods of match play differ between successful and less-successful teams playing at an elite standard.

Methods:

Movement was recorded using a MinimaxX global positioning system (GPS) unit sampling at 10 Hz during 25 rugby league matches, equating to 200 GPS files. Data for each half of match play were separated into 8 equal periods. These periods represented the most intense phase of match play (peak period), the period after the most intense phase of match play (subsequent period), and the average demands of all other periods in a match (mean period). Two rugby league teams were split into a high-success and a low-success group based on their success rates throughout their season.

Results:

Compared with their less-successful counterparts, adjustables and hit-up forwards from the high-success team covered less total distance (P < .01) and less high-intensity-running distance (P < .01) and were involved in a greater number of collisions (P < .01) during the mean period of match play.

Conclusions:

Although a greater number of collisions during match play is linked with a greater rate of success, greater amounts of high-intensity running and total distance are not related to competitive success in elite rugby league. These results suggest that technical and tactical differences, rather than activity profiles, may be the distinguishing factor between successful and less-successful rugby league teams.
Enhancing Physical Performance in Elite Junior Tennis Players With a Caffeinated Energy Drink
Authors: Gallo-Salazar César , Areces Francisco , Abián-Vicén Javier , Lara Beatriz , Salinero Juan José , Gonzalez-Millán Cristina , Portillo Javier , Muñoz Victor , Juarez Daniel , Coso Juan Del
Published: August 2014

The aim of this study was to investigate the effectiveness of a caffeinated energy drink to enhance physical performance in elite junior tennis players. In 2 different sessions separated by 1 wk, 14 young (16 ± 1 y) elite-level tennis players ingested 3 mg caffeine per kg body mass in the form of an energy drink or the same drink without caffeine (placebo). After 60 min, participants performed a handgrip-strength test, a maximal-velocity serving test, and an 8 × 15-m sprint test and then played a simulated singles match (best of 3 sets). Instantaneous running speed during the matches was assessed using global positioning (GPS) devices. Furthermore, the matches were videotaped and notated afterward. In comparison with the placebo drink, the ingestion of the caffeinated energy drink increased handgrip force by ~4.2% ± 7.2% (P = .03) in both hands, the running pace at high intensity (46.7 ± 28.5 vs 63.3 ± 27.7 m/h, P = .02), and the number of sprints (12.1 ± 1.7 vs 13.2 ± 1.7, P = .05) during the simulated match. There was a tendency for increased maximal running velocity during the sprint test (22.3 ± 2.0 vs 22.9 ± 2.1 km/h, P = .07) and higher percentage of points won on service with the caffeinated energy drink (49.7% ± 9.8% vs 56.4% ± 10.0%, P = .07) in comparison with the placebo drink. The energy drink did not improve ball velocity during the serving test (42.6 ± 4.8 vs 42.7 ± 5.0 m/s, P = .49). The preexercise ingestion of caffeinated energy drinks was effective to enhance some aspects of physical performance of elite junior tennis players.
Use of differentiated pluripotent stem cells in replacement therapy for treating disease
Authors: Fox Ira J. , Daley George Q. , Goldman Steven A. , Huard Johnny , Kamp Timothy J. , Trucco Massimo
Published: August 2014

Challenges for stem cell–based therapies

Patient-derived pluripotent stem cells (PSCs) hold promise in the treatment of injury and disease. An ever-increasing number of specific cell types can be generated from PSCs, but technical challenges remain in applying these cells in the clinic. Fox
et al.
review the challenges in attaining this goal. These include gene modification, cell rejection, and delivery and localization issues involved in transplantation of cells for the treatment of diabetes and disorders of the blood, liver, heart, and brain.

Science
, this issue
10.1126/science.1247391
Electron microscopy of gold nanoparticles at atomic resolution
Authors: Azubel Maia , Koivisto Jaakko , Malola Sami , Bushnell David , Hura Greg L. , Koh Ai Leen , Tsunoyama Hironori , Tsukuda Tatsuya , Pettersson Mika , Häkkinen Hannu , Kornberg Roger D.
Published: August 2014

Detailed structure of a gold nanoparticle

Adding only a few atoms or changing the capping ligand can dramatically change the structure of individual metal nanoparticles. Azubel
et al.
used aberration-corrected transmission electron microscopy to derive a three-dimensional reconstruction of water-soluble gold nanoparticles. Small-angle x-ray scattering and other techniques have also corroborated this model. They used this to determine the atomic structure, which compared favorably with density functional theory calculations, without assuming any a priori structural knowledge or the use of model fitting.

Science
, this issue p.
909
Sunlight controls water column processing of carbon in arctic fresh waters
Authors: Cory Rose M. , Ward Collin P. , Crump Byron C. , Kling George W.
Published: August 2014

Illuminating the pathway to destruction

Arctic lakes are an important source of atmospheric CO
2
and therefore play a role in climate change. It is thus vital to know how the rapid Arctic warming will affect them. Cory
et al.
now show that light is the biggest culprit in the breakdown of carbon from thawing permafrost soils (see the Perspective by Tranvik). This carbon then moves out into Arctic lakes and streams. Contrary to previous expectations, these photochemical processes cause much more destruction of the organic molecules in fresh water than bacterial respiration does.

Science
, this issue p.
925
; see also p.
870
Boosting GDP growth by accounting for the environment
Authors: Muller Nicholas Z.
Published: August 2014

Including air pollution and greenhouse gas damages increases estimated U.S. growth
Varying planetary heat sink led to global-warming slowdown and acceleration
Authors: Chen Xianyao , Tung Ka-Kit
Published: August 2014

Deep-sea warming slows down global warming

Global warming seems to have paused over the past 15 years while the deep ocean takes the heat instead. The thermal capacity of the oceans far exceeds that of the atmosphere, so the oceans can store up to 90% of the heat buildup caused by increased concentrations of greenhouse gases such as carbon dioxide. Chen and Tung used observational data to trace the pathways of recent ocean heating. They conclude that the deep Atlantic and Southern Oceans, but not the Pacific, have absorbed the excess heat that would otherwise have fueled continued warming.

Science
, this issue p.
897
Efficacy of inactivated poliovirus vaccine in India
Authors: Jafari Hamid , Deshpande Jagadish M. , Sutter Roland W. , Bahl Sunil , Verma Harish , Ahmad Mohammad , Kunwar Abhishek , Vishwakarma Rakesh , Agarwal Ashutosh , Jain Shilpi , Estivariz Concepcion , Sethi Raman , Molodecky Natalie A. , Grassly Nicholas C. , Pallansch Mark A. , Chatterjee Arani , Aylward R. Bruce
Published: August 2014

Two vaccines together are better than one alone

Polio is proving difficult to eradicate. Making the choice between administering a live attenuated vaccine orally (Sabin) or an inactivated vaccine (Salk) by injection has been highly controversial. Patients prefer the Sabin vaccine, but it requires many doses to offer immunity. Jafari
et al.
tested the two vaccines together in northern India. The injected vaccine significantly reduced virus shedding and boosted intestinal mucosal immunity in children already given the oral vaccine. Thus, using both vaccines could help speed the eventual global demise of polio.

Science
, this issue p.
922
RETRACTED: Chemically mediated behavior of recruiting corals and fishes: A tipping point that may limit reef recovery
Authors: Dixson Danielle L. , Abrego David , Hay Mark E.
Published: August 2014

Corals and reef fish choose nice homes

Young animals tend to disperse into new habitats. Can we use populations in protected areas to colonize nearby recovering or overused habitats? It seems that for corals and reef fish, the answer may be no. Dixson
et al.
show that dispersing juvenile corals and reef fish were overwhelmingly attracted to healthy reefs but were repelled by seaweeds that colonize degraded reefs (see the Perspective by Bruno). Thus, even species that appear passive in their choice of habitat may have stronger preferences than we thought.

Science
, this issue p.
892
; see also p.
879
Evolution of sweet taste perception in hummingbirds by transformation of the ancestral umami receptor
Authors: Baldwin Maude W. , Toda Yasuka , Nakagita Tomoya , O'Connell Mary J. , Klasing Kirk C. , Misaka Takumi , Edwards Scott V. , Liberles Stephen D.
Published: August 2014

The makings of a powerful sweet tooth

The main attraction of nectar, a hummingbird favorite, is the sweet taste of sugar. Oddly, though, birds lack the main vertebrate receptor for sweet taste, TIR2. Baldwin
et al.
show that a related receptor, TIR1-T1R3, which generally controls savory taste in vertebrates, adapts in hummingbirds to detect sweet (see the Perspective by Jiang and Beauchamp). This repurposing probably allowed hummingbirds to specialize in nectar feeding and may have assisted the evolution of the many and varied hummingbird species seen today.

Science
, this issue p.
929
; see also p.
878
Imprint of an ancient conflagration
Authors: Bromm Volker
Published: August 2014

Evidence is found for the massive stars that populated the early universe

[Also see Report by

Aoki
et al.

]
Riboswitch regulates RNA
Authors: Chen Jiandong , Gottesman Susan
Published: August 2014

Nutrient metabolism in bacteria is controlled by a circuit in which RNA is regulated by RNA

[Also see Reports by

DebRoy
et al.

and

Mellin
et al.

]
Sensing nectar's sweetness
Authors: Jiang Peihua , Beauchamp Gary K.
Published: August 2014

A taste receptor evolves to sense sugar in adapting to the diet of some birds

[Also see Report by

Baldwin
et al.

]
Joep Lange (1954–2014)
Authors: Goudsmit Jaap
Published: August 2014

A leader in developing therapy for AIDS is tragically killed
Is Atlantic holding Earth's missing heat?
Authors: Kintisch Eli
Published: August 2014

New leads in the hunt to explain the global warming hiatus.
A one-two punch against polio
Authors: Roberts Leslie
Published: August 2014

The once-sidelined injected vaccine could boost eradication.
Wheels when you need them
Authors: Wald Chelsea
Published: August 2014

Can special algorithms help keep shared bicycles rolling?.
Wolves cooperate but dogs submit, study suggests
Authors: Morell Virginia
Published: August 2014

Breeding for dependence, not cooperation, may have driven initial dog domestication.
The transferrable postdoc
Authors: Powell Kendall
Published: August 2014

Now more than ever, experts say, postdoctoral fellows need to cultivate a broad base of beyond-the-bench skills and capitalize on transferring them to the next stage of their career to be as competitive as possible. In today's competitive job market, it is vitally important for postdocs to accumulate skill sets on their CVs right alongside their publications–whether their next career move is research-based or not. Postdocs who repurpose their lab leadership and project management skills into star candidate qualities have an advantage when looking to step into their next position.
Fusion Protein Comprising Factor H Domains 6 and 7 and Human IgG1 Fc as an Antibacterial Immunotherapeutic
Authors: Shaughnessy Jutamas , Vu David M. , Punjabi Rahi , Serra-Pladevall Judit , DeOliveira Rosane B. , Granoff Dan M. , Ram Sanjay
Published: August 2014

The emergence of antimicrobial resistance among several medically important pathogens represents a serious threat to human health globally and necessitates the development of novel therapeutics. Complement forms a key arm of innate immune defenses against invading pathogens. A mechanism of complement evasion employed by many pathogens is binding of complement inhibitors, including factor H (FH), a key downregulator of the alternative pathway. Most FH-binding bacteria engage FH through regions in FH spanned by domains 6 and 7 and/or 18 through 20. We created a chimeric protein that comprised human FH domains 6 and 7 fused to human IgG1 Fc (FH6,7/HuFc) and tested its activity as an immunotherapeutic against
Neisseria meningitidis
, which binds FH through domains 6 and 7. FH6,7/HuFc bound to meningococci and effectively blocked FH binding to bacteria. FH6,7/HuFc enhanced human C3 and C4 deposition and facilitated complement-mediated killing in a dose-responsive manner; complement activation and killing were classical pathway dependent. To investigate
in vivo
efficacy, infant Wistar rats were treated intraperitoneally (IP) with different doses of FH6,7/HuFc and challenged 2 h later with serogroup C strain 4243 given IP. At 8 to 9 h after the challenge, the FH6,7/HuFc-treated rats had >100-fold fewer CFU per ml of blood than control animals pretreated with phosphate-buffered saline (PBS) or FH18–20/HuFc, which does not bind to meningococci (
P
< 0.0001). These data provide proof of concept of the utility of FH/Fc fusion proteins as anti-infective immunotherapeutics. Because many microbes share a common binding region(s) in FH, FH/Fc chimeric proteins may be a promising candidate for adjunctive therapy against drug-resistant pathogens.
Precision of Vancomycin and Daptomycin MICs for Methicillin-Resistant Staphylococcus aureus and Effect of Subculture and Storage
Authors: Charlton Carmen L. , Hindler Janet A. , Turnidge John , Humphries Romney M.
Published: August 2014

The reproducibility of vancomycin and daptomycin MICs, measured by broth microdilution (BMD) and Etest, was prospectively assessed for 10 methicillin-resistant
Staphylococcus aureus
(MRSA) isolates from the blood samples from patients on vancomycin therapy. The isolates were tested at the time of isolation from blood and following 5, 10, and 20 subcultures and at 1, 3, 6, and 12 months of storage at −70°C. The MICs were determined by Etest and BMD using two different manufacturers (BBL and Difco) of cation-adjusted Mueller-Hinton broth (CA-MHB), and using three different drug powders: vancomycin from Sigma, vancomycin from Novation, and daptomycin from Cubist. The antimicrobial concentrations tested were 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 μg/ml. Two isolates were vancomycin intermediate and daptomycin nonsusceptible, and two isolates had reduced susceptibility to vancomycin (BMD MIC, 1.5 or 2.0 μg/ml). The vancomycin MICs were significantly higher in the BBL CA-MHB than those in the Difco CA-MHB, and with Sigma versus Novation vancomycin powder. The daptomycin MICs were also significantly higher in the BBL CA-MHB. The Etest MICs were significantly higher than those obtained by BMD for vancomycin but not for daptomycin. The average precision of the vancomycin BMD MICs when analyzing 20 results was ±1.10-fold log
2
dilutions, and it was ±1.67-fold for daptomycin (10 results). The average precision for Etest was ±1.11-fold for vancomycin and ±1.16-fold for daptomycin. No significant change in MICs was noted following 5, 10, or 20 subcultures or at up to 6 months of frozen storage. However, the vancomycin MICs alone were significantly lower (0.74-fold) following 12 months of frozen storage. From these data, despite variations in CA-MHB and antimicrobial powder, the MIC result precision was <0.5 log
2
dilutions in a single laboratory, suggesting that testing interdilution MICs (e.g., MICs between serial 2-fold dilutions) is a possibility. A more accurate method for measuring vancomycin MIC results is thus possible, but further standardization of BMD testing would be required to achieve this goal.
Immunodeficient Mouse Models with Different Disease Profiles byIn VivoInfection with the Same Clinical Isolate of Enterovirus 71
Authors: Liao Chun-Che , Liou An-Ting , Chang Ya-Shu , Wu Szu-Yao , Chang Chih-Shin , Lee Chien-Kuo , Kung John T. , Tu Pang-Hsien , Yu Ya-Yen , Lin Chi-Yung , Lin Jen-Shiou , Shih Chiaho
Published: August 2014

Like poliovirus infection, severe infection with enterovirus 71 (EV71) can cause neuropathology. Unlike poliovirus, EV71 is often associated with hand-foot-and-mouth disease (HFMD). Here we established three mouse models for experimental infection with the same clinical isolate of EV71. The NOD/SCID mouse model is unique for the development of skin rash, an HFMD-like symptom. While the NOD/SCID mice developed limb paralysis and death at near-100% efficiency, the gamma interferon receptor knockout (ifngrKO) andstat-1knockout mice exhibited paralysis and death rates near 78% and 30%, respectively. Productive infection with EV71 depends on the viral dose, host age, and inoculation route. Levels of infectious EV71, and levels of VP1-specific RNA and protein in muscle, brain, and spinal cord, were compared side by side between the NOD/SCID andstat-1knockout models before, during, and after disease onset. Spleen fibrosis and muscle degeneration are common in the NOD/SCID andstat-1knockout models. The main differences between these two models include their disease manifestations and cytokine/chemokine profiles. The pathology of the NOD/SCID model includes (i) inflammation and expression of viral VP1 antigen in muscle, (ii) increased neutrophil levels and decreased eosinophil and lymphocyte levels, and (iii) hair loss and skin rash. The characteristic pathology of thestat-1knockout model includes (i) a strong tropism of EV71 for the central nervous system, (ii) detection of VP1 protein in the Purkinje layer of cerebellar cortex, pons, brain stem, and spinal cord, (iii) amplification of microglial cells, and (iv) dystrophy of intestinal villi. Our comparative studies on these new models with oral or intraperitoneal (i.p.) infection underscored the contribution of host immunity, including the gamma interferon receptor, to EV71 pathogenesis.

IMPORTANCEIn the past decade, enterovirus 71 (EV71) has emerged as a major threat to public health in the Asia-Pacific region. Disease manifestations include subclinical infection, common-cold-like syndromes, hand-foot-and-mouth disease (HFMD), uncomplicated brain stem encephalitis, severe dysregulation of the autonomic nerve system, fatal pulmonary edema, and cardiopulmonary collapse. To date, no effective vaccine or treatment is available. A user-friendly and widely accessible animal model for researching EV71 infection and pathogenesis is urgently needed by the global community, both in academia and in industry.
Autographa californica Multiple Nucleopolyhedrovirus
orf132
Encodes a Nucleocapsid-Associated Protein Required for Budded-Virus and Multiply Enveloped Occlusion-Derived Virus Production
Authors: Yang Ming , Wang Shuo , Yue Xiu-Li , Li Lu-Lin
Published: August 2014

Autographa californica
multiple nucleopolyhedrovirus
orf132
(named
ac132
) has homologs in all genome-sequenced group I nucleopolyhedroviruses. Its role in the viral replication cycle is unknown. In this study,
ac132
was shown to express a protein of around 28 kDa, which was determined to be associated with the nucleocapsids of both occlusion-derived virus and budded virus. Confocal microscopy showed that AC132 protein appeared in central region of the nucleus as early as 12 h postinfection with the virus. It formed a ring zone at the periphery of the nucleus by 24 h postinfection. To investigate its role in virus replication,
ac132
was deleted from the viral genome by using a bacmid system. In the Sf9 cell culture transfected by the
ac132
knockout bacmid, infection was restricted to single cells, and the titer of infectious budded virus was reduced to an undetectable level. However, viral DNA replication and the expression of late genes
vp39
and
odv-e25
and a reporter gene under the control of the very late gene
p10
promoter were unaffected. Electron microscopy showed that nucleocapsids, virions, and occlusion bodies were synthesized in the cells transfected by an
ac132
knockout bacmid, but the formation of the virogenic stroma and occlusion bodies was delayed, the numbers of enveloped nucleocapsids were reduced, and the occlusion bodies contained mainly singly enveloped nucleocapsids. AC132 was found to interact with envelope protein ODV-E18 and the viral DNA-binding protein P6.9. The data from this study suggest that
ac132
possibly plays an important role in the assembly and envelopment of nucleocapsids.

IMPORTANCE
To our knowledge, this is the first report on a functional analysis of
ac132
. The data presented here demonstrate that
ac132
is required for production of the budded virus and multiply enveloped occlusion-derived virus of
Autographa californica
multiple nucleopolyhedrovirus. This article reveals unique phenotypic changes induced by
ac132
deletion on the virus and multiple new findings on
ac132
.
Establishment and Characterization of a Lethal Mouse Model for the Angola Strain of Marburg Virus
Authors: Qiu Xiangguo , Wong Gary , Audet Jonathan , Cutts Todd , Niu Yulian , Booth Stephanie , Kobinger Gary P.
Published: August 2014

Infections with Marburg virus (MARV) and Ebola virus (EBOV) cause severe hemorrhagic fever in humans and nonhuman primates (NHPs) with fatality rates up to 90%. A number of experimental vaccine and treatment platforms have previously been shown to be protective against EBOV infection. However, the rate of development for prophylactics and therapeutics against MARV has been lower in comparison, possibly because a small-animal model is not widely available. Here we report the development of a mouse model for studying the pathogenesis of MARV Angola (MARV/Ang), the most virulent strain of MARV. Infection with the wild-type virus does not cause disease in mice, but the adapted virus (MARV/Ang-MA) recovered from liver homogenates after 24 serial passages in severe combined immunodeficient (SCID) mice caused severe disease when administered intranasally (i.n.) or intraperitoneally (i.p.). The median lethal dose (LD
50
) was determined to be 0.015 50% TCID
50
(tissue culture infective dose) of MARV/Ang-MA in SCID mice, and i.p. infection at a dose of 1,000× LD
50
resulted in death between 6 and 8 days postinfection in SCID mice. Similar results were obtained with immunocompetent BALB/c and C57BL/6 mice challenged i.p. with 2,000× LD
50
of MARV/Ang-MA. Virological and pathological analyses of MARV/Ang-MA-infected BALB/c mice revealed that the associated pathology was reminiscent of observations made in NHPs with MARV/Ang. MARV/Ang-MA-infected mice showed most of the clinical hallmarks observed with Marburg hemorrhagic fever, including lymphopenia, thrombocytopenia, marked liver damage, and uncontrolled viremia. Virus titers reached 10
8
TCID
50
/ml in the blood and between 10
6
and 10
10
TCID
50
/g tissue in the intestines, kidney, lungs, brain, spleen, and liver. This model provides an important tool to screen candidate vaccines and therapeutics against MARV infections.

IMPORTANCE
The Angola strain of Marburg virus (MARV/Ang) was responsible for the largest outbreak ever documented for Marburg viruses. With a 90% fatality rate, it is similar to Ebola virus, which makes it one of the most lethal viruses known to humans. There are currently no approved interventions for Marburg virus, in part because a small-animal model that is vulnerable to MARV/Ang infection is not available to screen and test potential vaccines and therapeutics in a quick and economical manner. To address this need, we have adapted MARV/Ang so that it causes illness in mice resulting in death. The signs of disease in these mice are reminiscent of wild-type MARV/Ang infections in humans and nonhuman primates. We believe that this will be of help in accelerating the development of life-saving measures against Marburg virus infections.
Novel Denisovan and Neanderthal Retroviruses
Authors: Lee Adam , Huntley Derek , Aiewsakun Pakorn , Kanda Ravinder K. , Lynn Claire , Tristem Michael
Published: August 2014

Following the recent availability of high-coverage genomes for Denisovan and Neanderthal hominids, we conducted a screen for endogenized retroviruses, identifying six novel, previously unreported HERV-K(HML2) elements (HERV-K is human endogenous retrovirus K). These elements are absent from the human genome (hg38) and appear to be unique to archaic hominids. These findings provide further evidence supporting the recent activity of the HERV-K(HML2) group, which has been implicated in human disease. They will also provide insights into the evolution of archaic hominids.