bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic bronchitis leads to accelerated hyperinflation in COPD patients during exercise
Authors: Zhang Wen , Lu Haitao , Peng Liyue , Ren Xiaoxia , Lu Yong , An Li , Zhang Hong , Tan Xiaoyue , Sun Xingguo , Huang Kewu
Published: March 2015

Background and objective

It is not known whether patients with chronic obstructive pulmonary disease (COPD) have a different exercise capacity with (CB+) or without accompanying chronic bronchitis (CB−).

Methods

We conducted spirometry, a 6‐min walk distance test and cardiopulmonary exercise test in 50 age‐matched healthy control subjects, 45 COPD patients without CB (CB−) and 37 COPD patients with CB (CB+). A multiple regression model was established to identify factors independently associated with peak oxygen consumption ().

Results

Patients with and without CB had similar forced expiratory volume in 1 s (FEV1). CB+ patients had a lower . CB+ and CB− participants had similar increases in tidal volume at peak exercise; however, CB+ patients had an increased respiratory rate (RR). These patients reached the peak value for ratio of end‐expiratory lung volume to total lung capacity (TLC) at a lower work load. A stepwise multiple linear regression analysis identified chronic bronchitis, FEV1, diffusing capacity for carbon monoxide, the ratio of residual volume to TLC and serum tumour necrosis factor‐α as independent predictors of peak .

Conclusions

CB significantly lowers exercise capacity in COPD patients because of dynamic hyperinflation during exercise. The accelerated dynamic hyperinflation may contribute to increased airway and systemic inflammation in COPD patients.
Pre‐existing Arterial Micro‐Calcification Predicts Primary Unassisted Arteriovenous Fistula Failure in Incident Hemodialysis Patients
Authors: Choi Su Jin , Yoon Hye Eun , Kim Young Soo , Yoon Sun Ae , Yang Chul Woo , Kim Yong‐Soo , Park Sun Cheol , Kim Young Ok
Published: March 2015

Vascular access micro‐calcification is a risk factor for cardiovascular morbidity and mortality in hemodialysis (HD) patients but its influence on vascular access patency is still undetermined. Our study aimed to determine the impact of arterial micro‐calcification (AMiC) on the patency of vascular access in HD patients. One‐hundred fourteen HD patients receiving arteriovenous fistula (AVF) operation were included in this study. During the operation, we obtained partial arterial specimen and performed pathological examination by von Kossa stain to identify AMiC. We compared primary unassisted AVF failure within 1 year between positive and negative AMiC groups, and performed Cox regression analysis for evaluating risk factor of AVF failure. The incidence of AMiC was 37.7% and AVF failure occurred in 45 patients (39.5%). The AVF failure rate within 1 year was greater in the positive AMiC group than those in the negative AMiC group (53.5% vs. 31.0%, p = 0.02). Kaplan–Meier analysis showed that the positive AMiC group had a lower AVF patency rate than the negative AMiC group (p = 0.02). The presence of AMiC was an independent risk factor for AVF failure. In conclusion, preexisting AMiC of the vascular access is associated with primary unassisted AVF failure in incident HD patients.
A new HLA‐B allele, B*49:34, sequenced in a Spanish individual
Authors: Azcarate M. , Santos S. , Balas A. , Eguizabal C. , Vicário J. L.
Published: March 2015

HLA‐B*49:34 shows one nucleotide difference regarding B*49:01:01 at codon 66 (ATC>GTC, I66>V66).
How bioturbation obscured the Cretaceous–Palaeogene boundary record
Authors: Alegret Laia , Rodríguez‐Tovar Francisco J. , Uchman Alfred
Published: March 2015

The Cretaceous–Palaeogene (K/Pg) boundary interval is often penetrated by burrows, which may obscure stratigraphic and micropalaeontological records, leading to misinterpretations of the sequence of events spanning the K/Pg boundary. Here, we assess the role of burrowing organisms in the redistribution of benthic foraminifera across the boundary at Bidart (France), and report a strong relationship between the behaviour represented by pre‐ and post‐K/Pg trace fossils and their benthic foraminiferal content. We further infer a brief interval of eutrophic conditions at the seafloor, as reported from other locations, which disappeared from the lowermost Danian stratigraphic record and is represented only inside post‐K/Pg trace fossils hosted in Cretaceous strata. The combined study of trace fossils and microfossils is a powerful tool in eco‐stratigraphy and event‐stratigraphy, and can yield important insights into the completeness of the K/Pg record, especially at locations such as Bidart where this interval has traditionally been assumed to be complete.
Phytotyping4D: a light‐field imaging system for non‐invasive and accurate monitoring of spatio‐temporal plant growth
Authors: Apelt Federico , Breuer David , Nikoloski Zoran , Stitt Mark , Kragler Friedrich
Published: March 2015

Integrative studies of plant growth require spatially and temporally resolved information from high‐throughput imaging systems. However, analysis and interpretation of conventional two‐dimensional images is complicated by the three‐dimensional nature of shoot architecture and by changes in leaf position over time, termed hyponasty. To solve this problem, Phytotyping4D uses a light‐field camera that simultaneously provides a focus image and a depth image, which contains distance information about the object surface. Our automated pipeline segments the focus images, integrates depth information to reconstruct the three‐dimensional architecture, and analyses time series to provide information about the relative expansion rate, the timing of leaf appearance, hyponastic movement, and shape for individual leaves and the whole rosette. Phytotyping4D was calibrated and validated using discs of known sizes, and plants tilted at various orientations. Information from this analysis was integrated into the pipeline to allow error assessment during routine operation. To illustrate the utility of Phytotyping4D, we compare diurnal changes in Arabidopsis thaliana wild‐type Col‐0 and the starchless pgm mutant. Compared to Col‐0, pgm showed very low relative expansion rate in the second half of the night, a transiently increased relative expansion rate at the onset of light period, and smaller hyponastic movement including delayed movement after dusk, both at the level of the rosette and individual leaves. Our study introduces light‐field camera systems as a tool to accurately measure morphological and growth‐related features in plants.
Anticoagulant rodenticide toxicity in six dogs presenting for ocular disease
Authors: Griggs Angela N. , Allbaugh Rachel A. , Tofflemire Kyle L. , Ben‐Shlomo Gil , Whitley David , Paulsen Michael E.
Published: March 2015

Objective

To describe cases of suspected anticoagulant rodenticide toxicity manifesting with predominantly ocular signs.

Materials and methods

Six canine cases that presented to veterinary referral hospitals for ocular abnormalities and were diagnosed with suspected or confirmed anticoagulant rodenticide ingestion were reviewed for commonalities in presentation and outcome.

Results

Five dogs had unilateral ocular signs and one dog had bilateral manifestations. Signs included subconjunctival hemorrhage, exophthalmos, and commonly orbital pain without other significant physical examination findings. Prothrombin time was measured in 5 of 6 dogs and was prolonged in all. Partial thromboplastin time was measured in 4 of 6 dogs and was prolonged in all. Complete blood cell count and serum chemistry profiles demonstrated mild, if any, abnormalities. Five dogs had known anticoagulant rodenticide exposure, and rodenticide ingestion was suspected in 1 additional case based on clinical signs, clinical pathologic abnormalities, and response to treatment. Five of 6 cases were hospitalized overnight for plasma transfusions along with oral or injectable vitamin K1, and all dogs were treated with oral vitamin K1 for 30 days. All dogs experienced complete resolution of clinical signs within 6 weeks of initiating treatment.

Conclusions

Anticoagulant rodenticide toxicity can present with predominantly ocular manifestations. Rodenticide ingestion should be considered in dogs with unilateral or bilateral subconjunctival hemorrhage, exophthalmos, and orbital pain.
MULTIDETECTOR‐ROW COMPUTED TOMOGRAPHIC CHARACTERISTICS OF PRESUMED PREURETERAL VENA CAVA IN CATS
Authors: Pey Pascaline , Marcon Oriana , Drigo Michele , Specchi Swan , Bertolini Giovanna
Published: March 2015

Preureteral vena cava (circumcaval ureter, retrocaval ureter) occurs in a third of the feline population and has been associated with ureteral strictures in humans. The aim of this retrospective cross‐sectional study was to describe the contrast‐enhanced multidetector row computed tomographic (MDCT) characteristics of presumed preureteral vena cava in a group of cats. Medical records from two institutions located in different continents were searched from 2010–2013 for cases with complete contrast‐enhanced MDCT examinations of the abdomen (i.e. included the entire course of the ureters and prerenal and renal segments of the caudal vena cava) and a diagnosis of preureteral caudal vena cava. For cases meeting inclusion criteria, CT scan data were retrieved and characteristics of the preureteral caudal vena cava were recorded. Presence of concomitant renal or ureteral diseases was also recorded. A total of 272 cats had contrast‐enhanced abdominal CT scans during the study period and of these, 68 cats (22.43 ± 4.96%) had a diagnosis of presumed preureteral vena cava. In all affected cats, a “reverse‐J ureter” was observed, i.e. a ureter running medially at the level of L4–5, passing dorsally to the caudal vena cava and then exiting ventrally between the caudal vena cava and aorta returning to its normal position. Having a preureteral vena cava resulted in an increased risk for concurrent urinary signs (OR = 3.00; CI: 95%; 1.28–6.99; P = 0.01). Findings supported the use of contrast‐enhanced MDCT for characterizing morphology of preureteral vena cava and its relation with ureters in cats.
Modeling and Experimental Validation of Actuating a Bistable Buckled Beam Via Moment Input
Authors: Cleary Jonathon , Su Hai-Jun
Published: March 2015

Bistable mechanisms have two stable equilibrium positions separated by a higher energy unstable equilibrium position. They are well suited for microswitches, microrelays, and many other macro- and micro-applications. This paper discusses a bistable buckled beam actuated by a moment input. A theoretical model is developed for predicting the necessary input moment. A novel experimental test setup was created for experimental verification of the model. The results show that the theoretical model is able to predict the maximum necessary input moment within 2.53%. This theoretical model provides a guideline to design bistable compliant mechanisms and actuators. It is also a computational tool to size the dimensions of buckled beams for actuating a specific mechanism.
A Compact, Bone-Attached Robot for Mastoidectomy
Authors: Dillon Neal P. , Balachandran Ramya , Fitzpatrick J. Michael , Siebold Michael A. , Labadie Robert F. , Wanna George B. , Withrow Thomas J. , Webster Robert J.
Published: March 2015

Otologic surgery often involves a mastoidectomy, which is the removal of a portion of the mastoid region of the temporal bone, to safely access the middle and inner ear. The surgery is challenging because many critical structures are embedded within the bone, making them difficult to see and requiring a high level of accuracy with the surgical dissection instrument, a high-speed drill. We propose to automate the mastoidectomy portion of the surgery using a compact, bone-attached robot. The system described in this paper is a milling robot with four degrees-of-freedom (DOF) that is fixed to the patient during surgery using a rigid positioning frame screwed into the surface of the bone. The target volume to be removed is manually identified by the surgeon pre-operatively in a computed tomography (CT) scan and converted to a milling path for the robot. The surgeon attaches the robot to the patient in the operating room and monitors the procedure. Several design considerations are discussed in the paper as well as the proposed surgical workflow. The mean targeting error of the system in free space was measured to be 0.5 mm or less at vital structures. Four mastoidectomies were then performed in cadaveric temporal bones, and the error at the edges of the target volume was measured by registering a postoperative computed tomography (CT) to the pre-operative CT. The mean error along the border of the milled cavity was 0.38 mm, and all critical anatomical structures were preserved.
Pressure Cycle Testing of Cr–Mo Steel Pressure Vessels Subjected to Gaseous Hydrogen
Authors: Yamabe Junichiro , Itoga Hisatake , Awane Tohru , Matsuo Takashi , Matsunaga Hisao , Matsuoka Saburo
Published: March 2015

Pressure cycle tests were performed on two types of Cr–Mo steel pressure vessels with notches machined on their inside under hydrogen-gas pressures, between 0.6 and 45 MPa at room temperature. Fatigue crack growth (FCG) and fracture toughness tests of the Cr–Mo steels samples from the vessels were also carried out in gaseous hydrogen. The Cr–Mo steels showed accelerated FCG rates in gaseous hydrogen compared to ambient air. The fracture toughness of the Cr–Mo steels in gaseous hydrogen was significantly smaller than that in ambient air. Four pressure vessels were tested with gaseous hydrogen. All pressure vessels failed by leak-before-break (LBB). The LBB failure of one pressure vessel could not be estimated by using the fracture toughness in gaseous hydrogen KIC,H; accordingly, the LBB assessment based on KIC,H is conservative and there is a possibility that KIC,H does not provide a reasonable assessment of LBB. In contrast, the fatigue lives of all pressure vessels could be estimated by using the accelerated FCG rates in gaseous hydrogen.
Stochastic Sampled-Data Control for H∞ Stabilization of Transport Reaction Systems
Authors: Rakkiyappan R. , Dharani S.
Published: March 2015

This paper investigates the problem of stochastic sampled-data H∞ control for a class of parabolic systems governed by one-dimensional semilinear transport reaction systems with external disturbances. A sampled-data controller design is developed by introducing the time-varying delay in the control input signals. The m sampling periods are considered whose occurrence probabilities are known constants and satisfy Bernoulli distribution. Since discontinuous Lyapunov functional copes well with problems of sampled-data control systems, a discontinuous Lyapunov functional is constructed based on the extended Wirtinger’s inequality. With this new approach, sufficient conditions that guarantee the asymptotic mean-square stabilization of the considered systems and the L2-gain analysis are derived in terms of linear matrix inequalities (LMIs), which can be solved by any of the available software.
Onset of Flash Atomization in a Propellant Microjet
Authors: Shemirani Farzin M. , Church Tanya K. , Lewis David A. , Finlay Warren H. , Vehring Reinhard
Published: March 2015

The parameters affecting the onset of flashing in microjets were studied. A custom atomizer assembly was designed to produce jets of propellant mixtures at different temperatures. Propellants chosen were HFA134a and HFA227ea, which are used in most pressurized metered dose inhalers (pMDIs). Ethanol was added to the propellants to investigate its effect on flashing. Orifices used ranged from 5 to 35 μm in diameter. A critical jet diameter above which flashing was the dominant mechanism of atomization was found at each temperature and formulation. A correlation was developed to relate the critical jet diameter to the thermophysical properties of the formulation.
Dynamics of Cricket Sound Production
Authors: Godthi Vamsy , Pratap Rudra
Published: March 2015

The clever designs of natural transducers are a great source of inspiration for man-made systems. At small length scales, there are many transducers in nature that we are now beginning to understand and learn from. Here, we present an example of such a transducer that is used by field crickets to produce their characteristic song. This transducer uses two distinct components—a file of discrete teeth and a plectrum that engages intermittently to produce a series of impulses forming the loading, and an approximately triangular membrane, called the harp, that acts as a resonator and vibrates in response to the impulse-train loading. The file-and-plectrum act as a frequency multiplier taking the low wing beat frequency as the input and converting it into an impulse-train of sufficiently high frequency close to the resonant frequency of the harp. The forced vibration response results in beats producing the characteristic sound of the cricket song. With careful measurements of the harp geometry and experimental measurements of its mechanical properties (Young's modulus determined from nanoindentation tests), we construct a finite element (FE) model of the harp and carry out modal analysis to determine its natural frequency. We fine tune the model with appropriate elastic boundary conditions to match the natural frequency of the harp of a particular species—Gryllus bimaculatus. We model impulsive loading based on a loading scheme reported in literature and predict the transient response of the harp. We show that the harp indeed produces beats and its frequency content matches closely that of the recorded song. Subsequently, we use our FE model to show that the natural design is quite robust to perturbations in the file. The characteristic song frequency produced is unaffected by variations in the spacing of file-teeth and even by larger gaps. Based on the understanding of how this natural transducer works, one can design and fabricate efficient microscale acoustic devices such as microelectromechanical systems (MEMS) loudspeakers.
Implementation Challenges and Solutions for Homogeneous Charge Compression Ignition Combustion in Diesel Engines
Authors: Asad Usman , Zheng Ming , Ting David S.-K. , Tjong Jimi
Published: March 2015

Homogeneous charge compression ignition (HCCI) combustion in diesel engines can provide cleaner operation with ultralow NOx and soot emissions. While HCCI combustion has generated significant attention in the last decade, however, till date, it has seen very limited application in production diesel engines. HCCI combustion is typically characterized by earlier than top-dead-center (pre-TDC) phasing, very high-pressure rise rates, short combustion durations, and minimal control over the timing of the combustion event. To offset the high reactivity of the diesel fuel, large amounts of exhaust gas recirculation (EGR) (30–60%) are usually applied to postpone the initiation of combustion, shift the combustion toward TDC, and alleviate to some extent, the high-pressure rise rates and the reduced energy efficiency. In this work, a detailed analysis of HCCI combustion has been carried out on a high-compression ratio (CR), single-cylinder diesel engine. The effects of intake boost, EGR quantity/temperature, engine speed, injection scheduling, and injection pressure on the operability limits have been empirically determined and correlated with the combustion stability, emissions, and performance metrics. The empirical investigation is extended to assess the suitability of common alternate fuels (n-butanol, gasoline, and ethanol) for HCCI combustion. On the basis of the analysis, the significant challenges affecting the real-world application of HCCI are identified, their effects on the engine performance quantified, and possible solutions to overcome these challenges explored through both theoretical and empirical investigations. This paper intends to provide a comprehensive summary of the implementation issues affecting HCCI combustion in diesel engines.
A New Numerical Method for Developing the Lumped Dynamic Model of Valve Train
Authors: Guo Jie , Cao Yipeng , Zhang Wenping , Zhang Xinyu
Published: March 2015

The dynamics of valve train is influenced by stiffness, size, and mass distribution of its components and initial valve clearance and so on. All the factors should be taken into consideration correctly by dynamic model and described qualitatively and quantitatively through mathematical variables. This paper proposes a new simplified method for valve train components, namely, mode matching method (MMM) for camshaft, pushrod, rocker arm, valve, and valve spring. In this method, the amount of lumped masses for each flexible component is determined based on its natural frequencies and the considered frequency range. As a result, the dynamic model of each component is required to match its low order modes within the considered frequency range. The basis of this method is that the contributions of each component to valve train vibration are mainly in the low order modes. The numerical model of valve train is verified by an experiment conducted on a motor driven valve train system.
Assessment of different sample preparation routes for mass spectrometric monitoring and imaging of lipids in bone cells via ToF-SIMS
Authors: Schaepe Kaija , Kokesch-Himmelreich Julia , Rohnke Marcus , Wagner Alena-Svenja , Schaaf Thimo , Wenisch Sabine , Janek Jürgen
Published: March 2015

In ToF-SIMS analysis, the experimental outcome from cell experiments is to a great extent influenced by the sample preparation routine. In order to better judge this critical influence in the case of lipid analysis, a detailed comparison of different sample preparation routines is performed—aiming at an optimized preparation routine for systematic lipid imaging of cell cultures. For this purpose, human mesenchymal stem cells were analyzed: (a) as chemically fixed, (b) freeze-dried, and (c) frozen-hydrated. For chemical fixation, different fixatives, i.e., glutaraldehyde, paraformaldehyde, and a mixture of both, were tested with different postfixative handling procedures like storage in phosphate buffered saline, water or critical point drying. Furthermore, secondary lipid fixation via osmium tetroxide was taken into account and the effect of an ascending alcohol series with and without this secondary lipid fixation was evaluated. Concerning freeze-drying, three different postprocessing possibilities were examined. One can be considered as a pure cryofixation technique while the other two routes were based on chemical fixation. Cryofixation methods known from literature, i.e., freeze-fracturing and simple frozen-hydrated preparation, were also evaluated to complete the comparison of sample preparation techniques. Subsequent data evaluation of SIMS spectra in both, positive and negative, ion mode was performed via principal component analysis by use of peak sets representative for lipids. For freeze-fracturing, these experiments revealed poor reproducibility making this preparation route unsuitable for systematic investigations and statistic data evaluation. Freeze-drying after cryofixation showed improved reproducibility and well preserved lipid contents while the other freeze-drying procedures showed drawbacks in one of these criteria. In comparison, chemical fixation techniques via glutar- and/or paraformaldehyde proved most suitable in terms of reproducibility and preserved lipid contents, while alcohol and osmium treatment led to the extraction of lipids and are therefore not recommended.
Use of cold atmospheric plasma in the treatment of cancer
Authors: Babington Parker , Rajjoub Kenan , Canady Jerome , Siu Alan , Keidar Michael , Sherman Jonathan H.
Published: March 2015

Cold atmospheric plasma (CAP) is an emerging modality for the treatment of solid tumors. In-vitro experiments have demonstrated that with increasing doses of plasma, tumor cells assays display decreased cell viability. CAP is theorized to induce tumor cells into apoptosis via multiple pathways including reactive oxygen and nitrogen species as well as cell cycle disruption. Studies have shown CAP treatment can decrease mouse model glioblastoma multiforme tumor volume by 56%, increase life span by 60%, and maintain up to 85% viability of normal cells. Emerging evidence suggests that CAP is a viable in-vivo treatment for a number of tumors, including glioblastoma, as it appears to selectively induce tumor cell death while noncancerous cells remain viable.
Comparison of crystalline-silicon/amorphous-silicon interface prepared by plasma enhanced chemical vapor deposition and catalytic chemical vapor deposition
Authors: Matsumura Hideki , Higashimine Koichi , Koyama Koichi , Ohdaira Keisuke
Published: March 2015

The properties of the interface between crystalline silicon (c-Si) and amorphous silicon (a-Si) were studied for two deposition methods of a-Si. One is the conventional plasma enhanced chemical vapor deposition (PECVD) and the other is catalytic chemical vapor deposition (Cat-CVD), often called hot-wire CVD. Surface recombination velocity (SRV) and atomic scale fine structure at the a-Si/c-Si interface were particularly studied. It is found that the a-Si/c-Si interface is very sharp for Cat-CVD a-Si and the width of transition-layer from c-Si to a-Si is less than 0.6 nm, which is three times smaller than for PECVD a-Si. It is also found that the SRV for Cat-CVD a-Si is about 1/3 of that for PECVD, and that the SRV appears to depend on the effective area of the interface which increases due to increase of surface roughness caused by plasma damage.
Dosimetric measurements of an n‐butyl cyanoacrylate embolization material for arteriovenous malformations
Authors: Labby Zacariah E. , Chaudhary Neeraj , Gemmete Joseph J. , Pandey Aditya S. , Roberts Donald A.
Published: March 2015

Purpose:

The therapeutic regimen for cranial arteriovenous malformations often involves both stereotactic radiosurgery and endovascular embolization. Embolization agents may contain tantalum or other contrast agents to assist the neurointerventionalists, leading to concerns regarding the dosimetric effects of these agents. This study investigated dosimetric properties of n‐butyl cyanoacrylate (n‐BCA) plus lipiodol with and without tantalum powder.

Methods:

The embolization agents were provided cured from the manufacturer with and without added tantalum. Attenuation measurements were made for the samples and compared to the attenuation of a solid water substitute using a 6 MV photon beam. Effective linear attenuation coefficients (ELAC) were derived from attenuation measurements made using a portal imager and derived sample thickness maps projected in an identical geometry. Probable dosimetric errors for calculations in which the embolized regions are overridden with the properties of water were calculated using the ELAC values. Interface effects were investigated using a parallel plate ion chamber placed at set distances below fixed samples. Finally, Hounsfield units (HU) were measured using a stereotactic radiosurgery CT protocol, and more appropriate HU values were derived from the ELAC results and the CT scanner's HU calibration curve.

Results:

The ELAC was 0.0516 ± 0.0063 cm−1 and 0.0580 ± 0.0091 cm−1 for n‐BCA without and with tantalum, respectively, compared to 0.0487 ± 0.0009 cm−1 for the water substitute. Dose calculations with the embolized region set to be water equivalent in the treatment planning system would result in errors of −0.29% and −0.93% per cm thickness of n‐BCA without and with tantalum, respectively. Interface effects compared to water were small in magnitude and limited in distance for both embolization materials. CT values at 120 kVp were 2082 and 2358 HU for n‐BCA without and with tantalum, respectively; dosimetrically appropriate HU values were estimated to be 79 and 199 HU, respectively.

Conclusions:

The dosimetric properties of the embolization agents are very close to those of water for a 6 MV beam. Therefore, treating the entire intracranial space as uniform in composition will result in less than 1% dosimetric error for n‐BCA emboli smaller than 3.4 cm without added tantalum and n‐BCA emboli smaller than 1.1 cm with added tantalum. Furthermore, when effective embolization can be achieved by the neurointerventionalist using n‐BCA without tantalum, the dosimetric impact of overriding material properties will be lessened. However, due to the high attenuation of embolization agents with and without added tantalum for diagnostic energies, artifacts may occur that necessitate additional imaging to accurately identify the spatial extent of the region to be treated.
Broken translational and rotational symmetry via charge stripe order in underdoped YBa
2
Cu
3
O
6+

y
Authors: Comin R. , Sutarto R. , da Silva Neto E. H. , Chauviere L. , Liang R. , Hardy W. N. , Bonn D. A. , He F. , Sawatzky G. A. , Damascelli A.
Published: March 2015

Picking out the elusive stripes

Copper-oxide superconductors have periodic modulations of charge density. Typically, the modulation is not the same for the whole crystal, but breaks up into small nanosized domains. Bulk experiments show that the density is modulated along both axes in the copper-oxide plane, but it is not clear whether this is true only on the scale of the whole crystal or also locally, for each domain. Comin
et al.
analyzed the charge order in the compound YBa
2
Cu
3
O
6+y
, using resonant x-ray scattering, and found that it was consistent with a local unidirectional, so-called stripy, ordering.

Science
, this issue p.
1335
The crucial role of surface magnetic fields for the solar dynamo
Authors: Cameron Robert , Schüssler Manfred
Published: March 2015

Sunspot cycle driven by linked fields

Sunspots indicate magnetic flux emerging at the Sun's surface. Sunspots change over an 11-year time scale, which depends on the behavior of the probable magnetic dynamo within. Cameron
et al.
suggest that the flux revealed by sunspot activity is effectively driven by the magnetic field strength at the Sun's poles. Their mathematical reasoning explains why the polar field activity can predict the sunspot cycle.

Science
, this issue p.
1333
Multidimensional hierarchical self-assembly of amphiphilic cylindrical block comicelles
Authors: Qiu Huibin , Hudson Zachary M. , Winnik Mitchell A. , Manners Ian
Published: March 2015

Cylindrical polymer micelles pack in 3D

When you control chemistry, solvents, temperature, and concentration, surfactants and block copolymers will readily assemble into micelles, rods, and other structures. Qiu
et al.
take this to new lengths through precise selection of longer polymer blocks that self-assemble through a crystallization process (see the Perspective by Lee
et al.
). They chose polymer blocks that were either hydrophobic or polar and used miscible solvents that were each ideal for only one of the blocks. Their triblock comicelles generated a wide variety of stable three-dimensional superstructures through side-by-side stacking and end-to-end intermicellar association.

Science
, this issue p.
1329
; see also p.
1310
MERS surges again, but pandemic jitters ease
Authors: Kupferschmidt Kai
Published: March 2015

The camel virus appears to be less lethal and more prevalent in humans than assumed.
New satellite radar could find 100,000 underwater mountains
Authors: Hand Eric
Published: March 2015

Better seamount maps could improve tsunami predictions and models of carbon mixing in the deep ocean.
Origin-of-life puzzle cracked
Authors: Service Robert F.
Published: March 2015

Study explains how three essential classes of molecules could have formed simultaneously.
Embryo engineering alarm
Authors: Vogel Gretchen
Published: March 2015

Researchers call for restraint in genome editing.
An RNA biosensor for imaging the first round of translation from single cells to living animals
Authors: Halstead James M. , Lionnet Timothée , Wilbertz Johannes H. , Wippich Frank , Ephrussi Anne , Singer Robert H. , Chao Jeffrey A.
Published: March 2015

Measuring translation in space and time

The ribosome translates the information contained within messenger RNAs (mRNAs) into proteins. When and where ribosomes encounter mRNAs can regulate gene expression. Halstead
et al.
developed an RNA biosensor that allows single molecules of mRNAs that have never been translated to be distinguished from ones that have undergone translation by the ribosome in living cells (see the Perspective by Popp and Maquat). The authors demonstrated the utility of their technique by examining the spatial and temporal regulation of translation in single cells and in
Drosophila
oocytes during development.

Science
, this issue p.
1367
; see also p.
1316
Creating a safe operating space for iconic ecosystems
Authors: Scheffer M. , Barrett S. , Carpenter S. R. , Folke C. , Green A. J. , Holmgren M. , Hughes T. P. , Kosten S. , van de Leemput I. A. , Nepstad D. C. , van Nes E. H. , Peeters E. T. H. M. , Walker B.
Published: March 2015

Manage local stressors to promote resilience to global change
Metabolic control of epilepsy
Authors: Scharfman Helen E.
Published: March 2015

Seizures may be controlled by targeting inexcitable elements of the nervous system

[Also see Report by

Sada
et al.

]
Actinomyces and Related Organisms in Human Infections
Authors: Könönen Eija , Wade William G.
Published: March 2015

Actinomyces israeliihas long been recognized as a causative agent of actinomycosis. During the past 3 decades, a large number of novelActinomycesspecies have been described. Their detection and identification in clinical microbiology laboratories and recognition as pathogens in clinical settings can be challenging. With the introduction of advanced molecular methods, knowledge about their clinical relevance is gradually increasing, and the spectrum of diseases associated withActinomycesandActinomyces-like organisms is widening accordingly; for example,Actinomyces meyeri,Actinomyces neuii, andActinomyces turicensisas well asActinotignum(formerlyActinobaculum)schaaliiare emerging as important causes of specific infections at various body sites. In the present review, we have gathered this information to provide a comprehensive and microbiologically consistent overview of the significance ofActinomycesand some closely related taxa in human infections.
Phosphorylation Controls the Nuclear-Cytoplasmic Shuttling of Influenza A Virus Nucleoprotein
Authors: Zheng Weinan , Li Jing , Wang Shanshan , Cao Shuaishuai , Jiang Jingwen , Chen Can , Ding Chan , Qin Chuan , Ye Xin , Gao George F. , Liu Wenjun
Published: March 2015

The nucleoprotein (NP) is a major component of the viral ribonucleoprotein (vRNP) complex. During the replication of influenza virus, the vRNP complex undergoes nuclear-cytoplasmic shuttling, during which NP serves as one of the determinants. To date, many phosphorylation sites on NP have been identified, but the biological functions of many of these phosphorylation sites remain unknown. In the present study, the functions of the phosphorylation sites S9, Y10, and Y296 were characterized. These residues are highly conserved, and their phosphorylation was essential for virus growth in cell culture and in a mouse model by regulating the activity of the viral polymerase and the nuclear-cytoplasmic shuttling of NP. The phosphorylation and dephosphorylation of S9 and Y10 controlled nuclear import of NP by affecting the binding affinity between NP and different isoforms of importin-α. In addition, the phosphorylation of Y296 caused nuclear retention of NP by reducing the interaction between NP and CRM1. Furthermore, tyrosine phosphorylation of NP during the early stage of virus infection was ablated when Y296 was mutated to F. However, at later stages of infection, it was weakened by the Y10F mutation. Taken together, the present data indicate that the phosphorylation and dephosphorylation of NP control the shuttling of NP between the nucleus and the cytoplasm during virus replication.

IMPORTANCE
It is well known that phosphorylation regulates the functions of viral proteins and the life cycle of influenza A virus. As NP is the most abundant protein in the vRNP complex of influenza A virus, several phosphorylation sites on this protein have been identified. However, the functions of these phosphorylation sites were unknown. The present study demonstrates that the phosphorylation status of these sites on NP can mediate its nuclear-cytoplasmic shuttling, which drives the trafficking of vRNP complexes in infected cells. The present data suggest that the phosphorylated residues of NP are multistep controllers of the virus life cycle and new targets for the design of anti-influenza drugs.
Diversity of Viruses Infecting the Green Microalga Ostreococcus lucimarinus
Authors: Derelle Evelyne , Monier Adam , Cooke Richard , Worden Alexandra Z. , Grimsley Nigel H. , Moreau Hervé
Published: March 2015

The functional diversity of eukaryotic viruses infecting a single host strain from seawater samples originating from distant marine locations is unknown. To estimate this diversity, we used lysis plaque assays to detect viruses that infect the widespread species
Ostreococcus lucimarinus
, which is found in coastal and mesotrophic systems, and
O. tauri
, which was isolated from coastal and lagoon sites from the northwest Mediterranean Sea. Detection of viral lytic activities against
O. tauri
was not observed using seawater from most sites, except those close to the area where the host strain was isolated. In contrast, the more cosmopolitan
O. lucimarinus
species recovered viruses from locations in the Atlantic and Pacific Oceans and the Mediterranean Sea. Six new
O. lucimarinus
viruses (OlVs) then were characterized and their genomes sequenced. Two subgroups of OlVs were distinguished based on their genetic distances and on the inversion of a central 32-kb-long DNA fragment, but overall their genomes displayed a high level of synteny. The two groups did not correspond to proximity of isolation sites, and the phylogenetic distance between these subgroups was higher than the distances observed among viruses infecting
O. tauri
. Our study demonstrates that viruses originating from very distant sites are able to infect the same algal host strain and can be more diverse than those infecting different species of the same genus. Finally, distinctive features and evolutionary distances between these different viral subgroups does not appear to be linked to biogeography of the viral isolates.

IMPORTANCE
Marine eukaryotic phytoplankton virus diversity has yet to be addressed, and more specifically, it is unclear whether diversity is connected to geographical distance and whether differential infection and lysis patterns exist among such viruses that infect the same host strain. Here, we assessed the genetic distance of geographically segregated viruses that infect the ubiquitous green microalga
Ostreococcus
. This study provides the first glimpse into the diversity of predicted gene functions in
Ostreococcus
viruses originating from distant sites and provides new insights into potential host distributions and restrictions in the world oceans.
A Japanese Encephalitis Virus Genotype 5 Molecular Clone Is Highly Neuropathogenic in a Mouse Model: Impact of the Structural Protein Region on Virulence
Authors: de Wispelaere Mélissanne , Frenkiel Marie-Pascale , Desprès Philippe
Published: March 2015

Japanese encephalitis virus (JEV) strains can be separated into 5 genotypes (g1 to g5) based on sequence similarity. JEV g5 strains have been rarely isolated and are poorly characterized. We report here the full characterization of a g5 virus generated using a cDNA-based technology and its comparison with a widely studied g3 strain. We did not observe any major differences between those viruses when their infectious cycles were studied in various cell lines
in vitro
. Interestingly, the JEV g5 strain was highly pathogenic when inoculated to BALB/c mice, which are known to be largely resistant to JEV g3 infection. The study of chimeric viruses between JEV g3 and g5 showed that there was a poor viral clearance of viruses that express JEV g5 structural proteins in BALB/c mice blood, which correlated with viral invasion of the central nervous system and encephalitis. In addition, using an
in vitro
model of the blood-brain barrier, we were able to show that JEV g5 does not have an enhanced capacity for entering the central nervous system, compared to JEV g3. Overall, in addition to providing a first characterization of the understudied JEV g5, our work highlights the importance of sustaining an early viremia in the development of JEV encephalitis.

IMPORTANCE
Genotype 5 viruses are genetically and serologically distinct from other JEV genotypes and can been associated with human encephalitis, which warrants the need for their characterization. In this study, we characterized the
in vitro
and
in vivo
properties of a JEV g5 strain and showed that it was more neuropathogenic in a mouse model than a well-characterized JEV g3 strain. The enhanced virulence of JEV g5 was associated with poor viral clearance but not with enhanced crossing of the blood-brain barrier, thus providing new insights into JEV pathogenesis.
Interventions to combat or prevent drug counterfeiting: a systematic review
Authors: El-Jardali Fadi , Akl Elie A , Fadlallah Racha , Oliver Sandy , Saleh Nadine , El-Bawab Lamya , Rizk Rana , Farha Aida , Hamra Rasha
Published: March 2015

Objective

Drug counterfeiting has serious public health and safety implications. The objective of this study was to systematically review the evidence on the effectiveness of interventions to combat or prevent drug counterfeiting.

Data sources

We searched multiple electronic databases and the grey literature up to March 2014. Two reviewers completed, in duplicate and independently, the study selection, data abstraction and risk of bias assessment.

Study eligibility criteria, participants and interventions

We included randomised trials, non-randomised studies, and case studies examining any intervention at the health system-level to combat or prevent drug counterfeiting. Outcomes of interest included changes in failure rates of tested drugs and changes in prevalence of counterfeit medicines. We excluded studies that focused exclusively on substandard, degraded or expired drugs, or that focused on medication errors.

Appraisal and synthesis

We assessed the risk of bias in each included study. We reported the results narratively and, where applicable, we conducted meta-analyses.

Results

We included 21 studies representing 25 units of analysis. Overall, we found low quality evidence suggesting positive effects of drug registration (OR=0.23; 95% CI 0.08 to 0.67), and WHO-prequalification of drugs (OR=0.06; 95% CI 0.01 to 0.35) in reducing the prevalence of counterfeit and substandard drugs. Low quality evidence suggests that licensing of drug outlets is probably ineffective (OR=0.66; 95% CI 0.41 to 1.05). For multifaceted interventions (including a mix of regulations, training of inspectors, public-private collaborations and legal actions), low quality evidence suggest they may be effective. The single RCT provided moderate quality evidence of no effect of ‘two extra inspections’ in improving drug quality.

Conclusions

Policymakers and stakeholders would benefit from registration and WHO-prequalification of drugs and may also consider multifaceted interventions. Future effectiveness studies should address the methodological limitations of the available evidence.

Trial registration number

PROSPERO CRD42014009269.
Neurodevelopmental outcomes at 7 years’ corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial
Authors: Collins Carmel T , Gibson Robert A , Anderson Peter J , McPhee Andrew J , Sullivan Thomas R , Gould Jacqueline F , Ryan Philip , Doyle Lex W , Davis Peter G , McMichael Judy E , French Noel P , Colditz Paul B , Simmer Karen , Morris Scott A , Makrides Maria
Published: March 2015

Objective

To determine if improvements in cognitive outcome detected at 18 months’ corrected age (CA) in infants born <33 weeks’ gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood.

Design

Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital.

Setting

Five Australian tertiary hospitals from 2008 to 2013.

Participants

626 of the 657 participants randomised between 2001 and 2005 were eligible to participate.

Interventions

High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2–4 days until term CA.

Primary outcome

Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted.

Results

604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital −0.3, 95% CI −2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet.

Conclusions

Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years’ CA.

Trial registration number

Australian New Zealand Clinical Trials Registry: ACTRN12606000327583.
Delivering OV training
Authors: Hay Sue
Published: March 2015

Sue Hay wanted to be a vet from her early teens – ‘no other career path stood a chance’ – but her determination was tested. After qualifying, she worked in practice, raised her family and then joined the State Veterinary Service. More recently she joined Improve International as Head of Practical Skills, delivering training and revalidation of Official Veterinarians
Early Seizure Detection Using Neuronal Potential Similarity: A Generalized Low-Complexity and Robust Measure
Authors: Bandarabadi Mojtaba , Rasekhi Jalil , Teixeira Cesar A. , Netoff Theoden I. , Parhi Keshab K. , Dourado Antonio
Published: March 2015

A novel approach using neuronal potential similarity (NPS) of two intracranial electroencephalogram (iEEG) electrodes placed over the foci is proposed for automated early seizure detection in patients with refractory partial epilepsy. The NPS measure is obtained from the spectral analysis of space-differential iEEG signals. Ratio between the NPS values obtained from two specific frequency bands is then investigated as a robust generalized measure, and reveals invaluable information about seizure initiation trends. A threshold-based classifier is subsequently applied on the proposed measure to generate alarms. The performance of the method was evaluated using cross-validation on a large clinical dataset, involving 183 seizure onsets in 1785 h of long-term continuous iEEG recordings of 11 patients. On average, the results show a high sensitivity of 86.9% (159 out of 183), a very low false detection rate of 1.4 per day, and a mean detection latency of 13.1 s from electrographic seizure onsets, while in average preceding clinical onsets by 6.3 s. These high performance results, specifically the short detection latency, coupled with the very low computational cost of the proposed method make it adequate for using in implantable closed-loop seizure suppression systems.