bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Bidirectionality of Emotion Understanding and Classroom Behavior with Spanish‐ and English‐speaking Preschoolers Attending Head Start
Authors: Strand Paul S. , Barbosa‐Leiker Celestina , Arellano Piedra Maria , Downs Andrew
Published: February 2015

The present study investigated time‐dependent relationships between emotion understanding and the behavioral adjustment of preschoolers over a single school year using a latent variable structural equation modeling framework. Teacher reports of child behavior (hyperactivity, emotion symptoms, conduct problems, peer problems, and prosocial behavior) and performance assessments of emotion understanding were obtained twice at a 6‐month interval for a sample of 281 preschoolers (159 boys and 122 girls, with mean age = 52.40 months) from English‐ (N = 158) and Spanish‐speaking (N = 123) backgrounds. Emotion understanding and behavior were stable over time, and cross‐sectional associations between them were in expected directions. Cross‐lagged paths revealed that the behavior variables significantly associated with emotion understanding across time were hyperactivity, emotion symptoms, and peer problems, and that behavior variables were generally better predictors of emotion understanding than vice versa. Differences across gender and language groups suggest a stronger and more complex bidirectional relationship between emotion understanding and behavior for girls and for Spanish‐speaking children compared wth boys and English‐speaking children. Results are discussed with respect to the value of exploring cross‐lagged relationships and the potential importance of gender and culture as determinants of those relationships.
Dimensions of Parenting Associated with Child Prekindergarten Emotion Regulation and Attention Control in Low‐income Families
Authors: Mathis Erin T. B. , Bierman Karen L.
Published: February 2015

Delays in emotion regulation and attention control are common among children growing up in poverty, and they contribute to significant socioeconomic gaps in school readiness and later school attainment. In this study, the emotion regulation and attention control skills of 210 prekindergarten Head Start participants were assessed (M age = 4.80 years old). Home interviews and videotaped parent–child interactions were used to evaluate three aspects of parenting (e.g., warm‐sensitive, directive‐critical, and parenting stress). Structural equation models documented significant, unique associations linking directive‐critical parenting and parenting stress with poor child emotion regulation skills. Directive‐critical parenting was also uniquely associated with low levels of child attention control. Warm‐sensitive parenting was not uniquely related to either emotion regulation or attention control at this age. The findings suggest that, by prekindergarten, parent stress management and reduced directiveness emerge as the primary correlates of child emotion regulation and attention control whereas warm‐sensitive parenting plays a diminished role.
In search of ‘lost’ knowledge and outsourced expertise in flood risk management
Authors: Haughton Graham , Bankoff Greg , J Coulthard Tom
Published: February 2015

This paper examines the parallel discourses of ‘lost’ local flood expertise and the growing use of commercial consultancies to outsource aspects of flood risk work. We critically examine the various claims and counter‐claims about lost, local and external expertise in flood management, focusing on the aftermath of the 2007 floods in East Yorkshire, England. Drawing on interviews with consultants, drainage engineers and others, we caution against claims that privilege ‘local’ floods knowledge as ‘good’ and expert knowledge as somehow suspect. This paper urges carefulness in interpreting claims about local knowledge, arguing that it is important always to think instead of hybrid knowledge formations. We conclude by arguing that experiments in the co‐production of flood risk knowledge need to be seen as part of a spectrum of ways for producing shared knowledge.
How we handled the dextran shortage: an alternative washing or dilution solution for cord blood infusions
Authors: Reich‐Slotky Ronit , Bachegowda Lohith S. , Ancharski Michael , Mendeleyeva Lyubov , Rubinstein Pablo , Rennert Hanna , Shore Tsiporah , van Besien Koen , Cushing Melissa
Published: February 2015

Dextran 40 is the main component of the solution used to wash or dilute thawed cord blood unit (CBU) products for stem cell transplant. Dextran 40 became unavailable in the United States as of April 2014. Like many other cellular therapy laboratories in the United States, we found ourselves with limited dextran 40 inventory, a growing CBU transplant requirement, and no alternative solution. Since there are no published alternative washing solutions for cryopreserved CBU we had to develop and validate a new solution rapidly. We chose to validate hydroxyethyl starch (HES) due to its similar ability to stabilize red blood cells and reduce sudden changes in osmolality that occur during thawing. For the validation we used 3 CBUs and thawed and washed each unit with both dextran 40– and HES‐based solutions; thus, each CBU served as its own control. We observed no significant differences between the two wash solutions for all the monitored variables including cell viability, cell recovery, or potency measured by colony‐forming cell assay. Based on this initial validation we began using HES‐albumin for CBU washing after our supply was exhausted. Our initial experience with the first 16 CBU transplants after validation indicates safe infusion and preliminary cord engraftment.
EQOFIX: a combined economic and quality‐of‐life study of hemophilia B treatments in France
Authors: Polack Benoît , Calvez Thierry , Chambost Hervé , Rothschild Chantal , Goudemand Jenny , Claeyssens Ségolène , Borel‐Derlon Annie , Bardoulat Isabelle , Maurel Frédérique , Woronoff‐Lemsi Marie‐Christine ,   for the EQOFIX Study Group
Published: February 2015

BACKGROUND

EQOFIX is a medicoeconomic study that analyzed the health‐related quality of life (HRQoL) and costs of care of the moderate and severe forms of hemophilia B, treated on demand or by prophylaxis with either plasma‐derived Factor IX (pdFIX) or recombinant FIX (rFIX).

STUDY DESIGN AND METHODS

The primary objectives were evaluations of the impact of hemophilia B on HRQoL and of the costs associated with its management. The secondary objectives were evaluations of the clinical efficacy and costs of care of pdFIX and rFIX. In this observational study we included and followed for 1 year severe and moderate hemophilia B patients without inhibitor. HRQoL was evaluated through generic and disease‐specific questionnaires. Information on the health resources consumed was collected every 3 months.

RESULTS

The EQOFIX cohort was composed of 155 patients, including 51 children and 104 adults, with 114 having severe disease and 41 having moderate disease. The regimens were prophylactic for 61 and on demand for 94. Altogether, 78 were treated with rFIX and 77 with pdFIX. There was no difference in the QoL between the pdFIX and rFIX treatments. The extra cost of prophylaxis was €22,605 per bleeding event prevented. The consumption of FIX was 1.4‐fold higher for the patients treated with rFIX than for the patients treated with pdFIX.

CONCLUSION

Our findings in a cohort composed of 25% of the French population of moderate and severe hemophilia B patients show, with similar clinical and HRQoL results, that treatment with rFIX is more expensive than treatment with pdFIX.
Evaluation of Osteogenic Potentials of Avian Demineralized Bone Matrix in the Healing of Osseous Defects in Pigeons
Authors: Sanaei Reza , Abu Jalila , Nazari Mojgan , Zuki Mohd A. B. , Allaudin Zeenathul N.
Published: February 2015

Objectives

To evaluate avian allogeneic demineralized bone matrix (DBM) in the healing of long bone defects as a function of geometry and time in a pigeon model.

Study Design

Experimental.

Animals

Adult rock pigeons (n = 60).

Methods

Midshaft ulnar osseous defects were grafted with 2 geometric forms of DBM (tubular vs. chipped) and stabilized with a hybrid fixator. Autologous chips of sternal keel were used in a third group as control. Outcomes were evaluated by radiography and histology/histomorphometry at 4, 8, 12, and 24 weeks postoperatively.

Results

Despite an early rapid healing response, autografts plateaued (histologic score and new bone area) by 8 weeks with no significant improvement afterwards. Conversely, allogeneic DBM implants demonstrated continuous temporal improvement in bone healing, and tubular DBM finally outpaced autograft implants after week 12 with values for metrics achieving statistical significance by week 24. Chip DBM was inferior to tubular DBM and autograft.

Conclusions

Avian DBM is osteogenic, biocompatible, and safe in orthotopic sites with potential usefulness in avian bone grafting. Implant geometry (shape and size) affects such osteogenic potentials.
The KCNQ1 channel – remarkable flexibility in gating allows for functional versatility
Authors: Liin Sara I. , Barro‐Soria Rene , Larsson H. Peter
Published: February 2015

The KCNQ1 channel (also called Kv7.1 or KvLQT1) belongs to the superfamily of voltage‐gated K+ (Kv) channels. KCNQ1 shares several general features with other Kv channels but also displays a fascinating flexibility in terms of the mechanism of channel gating, which allows KCNQ1 to play different physiological roles in different tissues. This flexibility allows KCNQ1 channels to function as voltage‐independent channels in epithelial tissues, whereas KCNQ1 function as voltage‐activated channels with very slow kinetics in cardiac tissues. This flexibility is in part provided by the association of KCNQ1 with different accessory KCNE β‐subunits and different modulators, but also seems like an integral part of KCNQ1 itself. The aim of this review is to describe the main mechanisms underlying KCNQ1 flexibility.
Cholesterol modulates open probability and desensitization of NMDA receptors
Authors: Korinek Miloslav , Vyklicky Vojtech , Borovska Jirina , Lichnerova Katarina , Kaniakova Martina , Krausova Barbora , Krusek Jan , Balik Ales , Smejkalova Tereza , Horak Martin , Vyklicky Ladislav
Published: February 2015

Key points

NMDA receptors (NMDARs) are tetrameric cation channels permeable to calcium; they mediate excitatory synaptic transmission in the CNS and their excessive activation can lead to neurodegeneration.

Although these receptors are in direct contact with plasma membrane, lipid–NMDAR interactions are little understood.

Using cultured rat cerebellar granule cells, we show that acute and chronic pretreatments resulting in cell cholesterol depletion profoundly diminish NMDAR responses and increase NMDAR desensitization, and also that cholesterol enrichment potentiates NMDAR responses; however, cholesterol manipulation has no effect on the amplitude of AMPA/kainate receptor responses.

Diminution of NMDAR responses by cholesterol depletion is the result of a reduction of the ion channel open probability, whereas the increase in receptor desensitization is the result of an increase in the rate constant of entry into the desensitized state.

These results demonstrate the physiological role of membrane lipids in the modulation of NMDAR activity.

NMDA receptors (NMDARs) are glutamate‐gated ion channels that mediate excitatory neurotransmission in the CNS. Although these receptors are in direct contact with plasma membrane, lipid–NMDAR interactions are little understood. In the present study, we aimed at characterizing the effect of cholesterol on the ionotropic glutamate receptors. Whole‐cell current responses induced by fast application of NMDA in cultured rat cerebellar granule cells (CGCs) were almost abolished (reduced to 3%) and the relative degree of receptor desensitization was increased (by seven‐fold) after acute cholesterol depletion by methyl‐β‐cyclodextrin. Both of these effects were fully reversible by cholesterol repletion. By contrast, the responses mediated by AMPA/kainate receptors were not affected by cholesterol depletion. Similar results were obtained in CGCs after chronic inhibition of cholesterol biosynthesis by simvastatin and acute enzymatic cholesterol degradation to 4‐cholesten‐3‐one by cholesterol oxidase. Fluorescence anisotropy measurements showed that membrane fluidity increased after methyl‐β‐cyclodextrin pretreatment. However, no change in fluidity was observed after cholesterol enzymatic degradation, suggesting that the effect of cholesterol on NMDARs is not mediated by changes in membrane fluidity. Our data show that diminution of NMDAR responses by cholesterol depletion is the result of a reduction of the open probability, whereas the increase in receptor desensitization is the result of an increase in the rate constant of entry into the desensitized state. Surface NMDAR population, agonist affinity, single‐channel conductance and open time were not altered in cholesterol‐depleted CGCs. The results of our experiments show that cholesterol is a strong endogenous modulator of NMDARs.
Describing Functions for Scalar Information Channels Subject to Quantization and Packet Loss
Authors: Gilbertson Eric , Hover Franz
Published: February 2015

Many of today's robot applications depend on wireless communications, whose performance can impact the whole system. To support analysis of feedback control through limited channels, we develop describing functions (DFs) for three variations on the series interconnection of a quantizer, a binary erasure channel, and decoder for a single input single output (SISO) system. The key steps in our derivation hold when the decoder is a linear-quadratic-Gaussian (LQG)-type control, a zero-output decoder, or a hold-output decoder. We confirm the accuracy of the new formulas and provide an example showing limit cycle behavior.
A Study of the Continuous Optimization Problem Using a Wood Robot Controlled by a Biologically Motivated System
Authors: Chen Jong-Chen
Published: February 2015

Continuous optimization plays an increasingly significant role in everyday decision-making situations. Our group had previously developed a multilevel system called the artificial neuromolecular system (ANM) that possessed structure richness allowing variation and/or selection operators to act on it in order to generate a broad range of dynamic behaviors. In this paper, we used the ANM system to control the motions of a wooden walking robot named Miky. The robot was used to investigate the ANM system's capability to deal with continuous optimization problems through self-organized learning. Evolutionary learning algorithm was used to train the system and generate appropriate control. The experimental results showed that Miky was capable of learning in a continued manner in a physical environment. A further experiment was conducted by making some changes to Miky's physical structure in order to observe the system's capability to deal with the change. Detailed analysis of the experimental results showed that Miky responded to the change by appropriately adjusting its leg movements in space and time. The results showed that the ANM system possessed continuous optimization capability in coping with the change. Our findings from the empirical experiments might provide us another dimension of information of how to design an intelligent system comparatively friendlier than the traditional systems in assisting humans to walk.
Heat Transfer and Pressure Drop Characteristics of Finned Metal Foam Heat Sinks Under Uniform Impinging Flow
Authors: Feng S. S. , Kuang J. J. , Lu T. J. , Ichimiya K.
Published: February 2015

A numerical investigation was carried out to characterize the thermal performance of finned metal foam heat sinks subject to an impinging air flow. The main objective of the study was to quantify the effects of all relevant configurational parameters (channel length, channel width, fin thickness, and fin height) of the heat sink upon the thermal performance. Open-cell aluminum foam having fixed porosity of 0.9118 and fixed pore density of five pores per inch (PPI) was used in the study. A previously validated model based on the porous medium approach was employed for the numerical simulation. Various simulation cases for different combinations of channel parameters were carried out to obtain the Nusselt number correlation. Based on the inviscid impinging flow, a pressure drop correlation was derived for impinging flow in finned metal foam heat sinks. By using these correlations, the thermal performance of finned metal foam heat sinks was compared with the conventional plate-fin heat sinks. It was demonstrated that the finned metal foam heat sinks outperformed the plate-fin heat sinks on the basis of given weight or given pumping power.
Optimization Using Arbitrary Lagrangian–Eulerian Formulation of the Navier–Stokes Equations
Authors: Helgason Eysteinn , Krajnović Siniša
Published: February 2015

In this paper, we present a new shape optimization method by using sensitivities obtained from the Arbitrary Lagrangian–Eulerian (ALE) form of the Navier–Stokes equations. In the ALE description, the nodes of the computational domain may be moved with the fluid as in the Lagrangian description, held fixed in space as in the Eulerian description, or moved in some arbitrary way in between. Applying the adjoint method with respect to mesh motion allows the whole sensitivity field for the shape changes to be calculated using only two solver calls, a primal solver call and an adjoint solver call. We show that the sensitivities with respect to the mesh motion can be calculated in a postprocessing step to the primal and adjoint flow simulations. The resulting ALE sensitivities are compared to sensitivities obtained using a finite difference approach. Finally, the sensitivities are coupled to a mesh motion smoothing algorithm, and a duct is optimized with respect to the total pressure drop using the proposed method.
The Effect of Initial Momentum Flux on the Circular Hydraulic Jump
Authors: Vishwanath K. P. , Dasgupta Ratul , Govindarajan Rama , Sreenivas K. R.
Published: February 2015

Earlier studies on the circular hydraulic jump have shown that the radial position of the hydraulic jump depends on the flow rate, gravity, and fluid viscosity. In this study, results from numerical simulations and experiments on circular hydraulic jumps are presented and through analysis, it is shown that the momentum flux is an additional controlling parameter in determining the jump location. Apart from the jump location, the variation of the film thickness with flow parameters is also obtained from experiments and numerical simulations. By including the dependence of the momentum flux and dissipation in the film along with other controlling parameters, the data on jump radius obtained from experiments and simulation (including the present study) covering a wide range of parameters reported in the literature can be collapsed on to a single curve.
Measurement of Fluid Flow Thickness Within a Rotating Cone
Authors: Symons Digby D. , Bizard Arnaud F. M.
Published: February 2015

This paper reports experimental measurements of film thickness for continuous fluid flow on the internal surface of a cone rotating about a vertical axis. Measurements were obtained via an optical method based on photographing the displacement of a grid projected onto the surface of the flow within the cone. Results are compared to analytical theory for axisymmetric, steady state, free-surface laminar flow of a Newtonian fluid in a spinning cone. The theory assumes that the flow is thin but takes account of gravity. The theoretical model is found to be in good agreement with the experimental results.
Nitrogen mass transfer models for plasma-based low-energy ion implantation
Authors: Zheng Bocong , Wang Kesheng , Zhang Zhipeng , Che Honglong , Lei Mingkai
Published: February 2015

The nitrogen mass transfer process in plasma-based low-energy ion implantation (PBLEII) is theoretically and experimentally studied in order to explore the process mechanism of PBLEII and therefore to optimize the apparatus design and the process conditions. An electron cyclotron resonance (ECR) microwave discharge generates the nitrogen plasma with a high density of 1011–1012 ions/cm3, which diffuses downstream to the process chamber along the divergent magnetic field. The nitrogen ions in the plasma implant into the surface and transport to the matrix of an austenitic stainless steel under the low negative pulsed bias of −2 kV at a process temperature of 400 °C. A global plasma model is used to simulate the ECR microwave plasma discharge for a range of working pressures and microwave powers. The fluid models are adopted to calculate the plasma downstream diffusion, the sheath expansion and the low-energy ion implantation on the surface. A nonlinear kinetic discrete model is established to describe the nitrogen transport in the austenitic stainless steel and the results are compared with the experimental measurements. Under an average implantation current density of 0.3–0.6 mA/cm2, the surface nitrogen concentration in the range from 18.5 to 29 at. % is a critical factor for the nitrogen transport in the AISI 304 austenitic stainless steel by PBLEII, which accelerates the implanted nitrogen diffusion inward up to 6–12 μm during a nitriding time of 4 h.
Plasmon-enhanced photocurrent of Ge-doped InGaO thin film transistors using silver nanoparticles
Authors: Park Si Jin , Lee Sang Moo , Kang Seong Jun , Lee Kwang-Ho , Park Jin-Seong
Published: February 2015

Germanium-doped indium-gallium oxide (GIGO) thin film transistors (TFTs) decorated with silver (Ag) nanoparticles (NPs) were prepared to study the plasmon effect. GIGO films of various thicknesses were deposited on SiO2/Si substrates, and Ag NPs (∼25 nm in diameter) were formed using a thermal evaporator and a postannealing process. The Ag NPs effectively absorbed light in the wavelength range of 500 and 600 nm, which corresponds to the plasmonic effect. Due to the plasmon resonance of Ag NPs, a significantly enhanced photocurrent was observed on the devices. The current increased by 348% with exposure to light when the Ag NPs were formed at the interface between the 10-nm-thick GIGO film and SiO2 substrate. The increased photocurrent revealed the presence of strong coupling between the localized plasmon and electrical carrier of the devices. The results show that the photocurrent of GIGO TFTs can be greatly enhanced when the plasmonic Ag NPs are located in the channel region of the devices.
Local patient dose diagnostic reference levels in pediatric interventional cardiology in Chile using age bands and patient weight values
Authors: Ubeda Carlos , Miranda Patricia , Vano Eliseo
Published: February 2015

Purpose:

To present the results of a patient dose evaluation program in pediatric cardiology and propose local diagnostic reference levels (DRLs) for different types of procedure and age range, in addition to suggesting approaches to correlate patient dose values with patient weight. This study was the first conducted in Latin America for pediatric interventional cardiology under the auspices of the International Atomic Energy Agency.

Methods:

Over three years, the following data regarding demographic and patient dose values were collected: age, gender, weight, height, number of cine series, total number of cine frames, fluoroscopy time (FT), and two dosimetric quantities, dose‐area product (DAP) and cumulative dose (CD), at the patient entrance reference point. The third quartile values for FT, DAP, CD, number of cine series, and the DAP/body weight ratio were proposed as the set of quantities to use as local DRLs.

Results:

Five hundred and seventeen patients were divided into four age groups. Sample sizes by age group were 120 for <1 yr; 213 for 1 to <5 yr; 82 for 5 to <10 yr; and 102 for 10 to <16 yr. The third quartile values obtained for DAP by diagnostic and therapeutic procedures and age range were 1.17 and 1.11 Gy cm2 for <1 yr; 1.74 and 1.90 Gy cm2 for 1 to <5 yr; 2.83 and 3.22 Gy cm2 for 5 to <10 yr; and 7.34 and 8.68 Gy cm2 for 10 to <16 yr, respectively. The third quartile value obtained for the DAP/body weight ratio for the full sample of procedures was 0.17 (Gy cm2/kg) for diagnostic and therapeutic procedures.

Conclusions:

The data presented in this paper are an initial attempt at establishing local DRLs in pediatric interventional cardiology, from a large sample of procedures for the standard age bands used in Europe, complemented with the values of the ratio between DAP and patient weight. This permits a rough estimate of DRLs for different patient weights and the refining of these values for the age bands when there may be large differences in child size. These DRLs were obtained at the largest pediatric hospital in Chile, with an active optimization program, and could be used by other hospitals in the Latin America region to compare their current patient dose values and determine whether corrective action is appropriate.
Computer aided wireless capsule endoscopy video segmentation
Authors: Li Baopu , Xu Guoqing , Zhou Ran , Wang Tianfu
Published: February 2015

Purpose:

Wireless capsule endoscopy (WCE) opens a new door for the digestive tract examination and diagnosis. However, the examination of its video data is tedious. This study aims to assist a physician to interpret a WCE video by segmenting it into different anatomic parts in the digestive tract.

Methods:

A two level WCE video segmentation scheme is proposed to locate the boundary between the stomach, small intestine, and large intestine. In the rough level, the authors utilize color feature to draw a dissimilarity curve for a WCE video and obtain an approximate boundary. Meanwhile, training data for the fine level segmentation can be collected automatically between the two approximate boundaries of organs to overcome the difficulty of training data collection in traditional approaches. In the fine level, color histogram in the HSI color space is used to segment the stomach and small intestine. Then, color uniform local binary pattern (CULBP) algorithm is applied for discrimination of the small intestine and large intestine, which includes two patterns, namely, color norm and color angle pattern. The CULBP feature is robust to variation of illumination and discriminative for classification. In order to increase the performance of support vector machine, the authors integrate it with the Adaboost approach. Finally, the authors refine the classification results to segment a WCE video into different parts, that is, the stomach, small intestine, and large intestine.

Results:

The average precision and recall are 91.2% and 90.6% for the stomach/small intestine classification, 89.2% and 88.7% for the small/large intestine discrimination. Paired t‐test also demonstrates a significant better performance of the proposed scheme compared to some traditional methods. The average segmentation error is 8 frames for the stomach/small intestine discrimination, and 14 frames for the small/large intestine segmentation.

Conclusions:

The results have demonstrated that the new video segmentation method can accurately locate the boundary between different organ regions in a WCE video. Such a segmentation result may enhance the efficiency of WCE examination.
Pervasive degeneracy and epistasis in a protein-protein interface
Authors: Podgornaia Anna I. , Laub Michael T.
Published: February 2015

Exploring the limits of protein sequence space

Exploring the variability of individual functional proteins is complicated by the vast number of combinations of possible amino acid sequences. Podgornaia and Laub take on this challenge by analyzing four amino acids critical for the interaction between two signaling proteins in
Escherichia coli.
They build all the possible 160,000 variants of one of the two proteins and find that over 1650 are functional. Even though there can be very high variability in the composition of the interface between the two proteins, there are nonetheless strong context-dependent constraints for some amino acids, which suggests why many functional variants are not seen in nature.

Science
, this issue p.
673
Programming colloidal phase transitions with DNA strand displacement
Authors: Rogers W. Benjamin , Manoharan Vinothan N.
Published: February 2015

DNA control of bonding interactions

Colloidal particles have been used as atom mimics and are often connected together using complementary DNA strands. Rogers and Manoharan controlled the strength of the colloidal “bond” by using a set of competing strand displacement reactions. They capitalized on the reversible chemical equilibrium between the DNA strands connecting different particles to control the temperature dependence of the equilibrium state.

Science
, this issue p.
639
Misfire aside, signs of cosmic inflation could come soon
Authors: Cho Adrian
Published: February 2015

Even as the BICEP result bites the dust, observers like their chances of spotting big-bang gravitational waves.
Africa's soil engineers: Termites
Authors: Pennisi Elizabeth
Published: February 2015

Kenyan plots show that termite mounds promote ecological health and may slow desertification.
Japanese neutrino physicists think really big
Authors: Normile Dennis
Published: February 2015

A proposed Hyper-Kamiokande would be the largest neutrino detector ever.
Where is Silicon Valley?
Authors: Guzman Jorge , Stern Scott
Published: February 2015

Forecasting and mapping entrepreneurial quality
Nanoscale temperature mapping in operating microelectronic devices
Authors: Mecklenburg Matthew , Hubbard William A. , White E. R. , Dhall Rohan , Cronin Stephen B. , Aloni Shaul , Regan B. C.
Published: February 2015

Plasmons can map temperature on the nanoscale

Determining temperature on small length scales can be challenging: Direct probes can alter sample temperature, and radiation probes are limited by the wavelength of the light used. Mecklenberg
et al.
show how the bulk plasmon resonance of aluminum can be used to map the temperature on the nanoscale with transmission electron microscopy (see the Perspective by Colliex). Many other metals and semiconductors also have plasmon resonances that could also be used for temperature imaging.

Science
, this issue p.
629
; see also p.
611
How a virus travels the world
Authors: Verhagen Josanne H. , Herfst Sander , Fouchier Ron A. M.
Published: February 2015

Wild birds may spread the H5N8 virus
Passing the CEO baton
Authors: Leshner Alan I.
Published: February 2015

s I retire from the office of chief executive of the American Association for the Advancement of Science (AAAS) and pass the baton to my very capable successor, physicist and former U.S. congressman Rush Holt, I have been reflecting on changes over the past decades both within the scientific enterprise and in its relationship with the rest of society. Many trends are cause for celebration, but others require remedial attention. On the positive side, new technologies have enabled new and very important scientific questions to be confronted, and a rise in collaborative, multidisciplinary science has fueled a remarkable pace of discovery. Science is also becoming more global in character as more countries invest in science and technology and fortify their infrastructures and science capacities. Science has never been more productive. And yet, the overall climate for science is more difficult than I have ever seen in my scientific career. This stunning state of contradiction indicates that there has never been a greater need, or a greater opportunity, for an international organization such as AAAS, whose mission is to advance science and serve society.
Efficacy of Human Papillomavirus 16 and 18 (HPV-16/18) AS04-Adjuvanted Vaccine against Cervical Infection and Precancer in Young Women: Final Event-Driven Analysis of the Randomized, Double-Blind PATRICIA Trial
Authors: Apter Dan , Wheeler Cosette M. , Paavonen Jorma , Castellsagué Xavier , Garland Suzanne M. , Skinner S. Rachel , Naud Paulo , Salmerón Jorge , Chow Song-Nan , Kitchener Henry C. , Teixeira Julio C. , Jaisamrarn Unnop , Limson Genara , Szarewski Anne , Romanowski Barbara , Aoki Fred Y. , Schwarz Tino F. , Poppe Willy A. J. , Bosch F. Xavier , Mindel Adrian , de Sutter Philippe , Hardt Karin , Zahaf Toufik , Descamps Dominique , Struyf Frank , Lehtinen Matti , Dubin Gary
Published: February 2015

We report final event-driven analysis data on the immunogenicity and efficacy of the human papillomavirus 16 and 18 ((HPV-16/18) AS04-adjuvanted vaccine in young women aged 15 to 25 years from the PApilloma TRIal against Cancer In young Adults (PATRICIA). The total vaccinated cohort (TVC) included all randomized participants who received at least one vaccine dose (vaccine,
n
= 9,319; control,
n
= 9,325) at months 0, 1, and/or 6. The TVC-naive (vaccine,
n
= 5,822; control,
n
= 5,819) had no evidence of high-risk HPV infection at baseline, approximating adolescent girls targeted by most HPV vaccination programs. Mean follow-up was approximately 39 months after the first vaccine dose in each cohort. At baseline, 26% of women in the TVC had evidence of past and/or current HPV-16/18 infection. HPV-16 and HPV-18 antibody titers postvaccination tended to be higher among 15- to 17-year-olds than among 18- to 25-year-olds. In the TVC, vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or greater (CIN1+), CIN2+, and CIN3+ associated with HPV-16/18 was 55.5% (96.1% confidence interval [CI], 43.2, 65.3), 52.8% (37.5, 64.7), and 33.6% (−1.1, 56.9). VE against CIN1+, CIN2+, and CIN3+ irrespective of HPV DNA was 21.7% (10.7, 31.4), 30.4% (16.4, 42.1), and 33.4% (9.1, 51.5) and was consistently significant only in 15- to 17-year-old women (27.4% [10.8, 40.9], 41.8% [22.3, 56.7], and 55.8% [19.2, 76.9]). In the TVC-naive, VE against CIN1+, CIN2+, and CIN3+ associated with HPV-16/18 was 96.5% (89.0, 99.4), 98.4% (90.4, 100), and 100% (64.7, 100), and irrespective of HPV DNA it was 50.1% (35.9, 61.4), 70.2% (54.7, 80.9), and 87.0% (54.9, 97.7). VE against 12-month persistent infection with HPV-16/18 was 89.9% (84.0, 94.0), and that against HPV-31/33/45/51 was 49.0% (34.7, 60.3). In conclusion, vaccinating adolescents before sexual debut has a substantial impact on the overall incidence of high-grade cervical abnormalities, and catch-up vaccination up to 18 years of age is most likely effective. (This study has been registered at
ClinicalTrials.gov
under registration no. NCT001226810.)
Development of a Competitive Enzyme-Linked Immunosorbent Assay for Detection of Antibodies against the 3B Protein of Foot-and-Mouth Disease Virus
Authors: Yang Ming , Parida Satya , Salo Tim , Hole Kate , Velazquez-Salinas Lauro , Clavijo Alfonso
Published: February 2015

Foot-and-mouth disease (FMD) is one of the most highly contagious and economically devastating diseases, and it severely constrains the international trade of animals. Vaccination against FMD is a key element in the control of FMD. However, vaccination of susceptible animals raises critical issues, such as the differentiation of infected animals from vaccinated animals. The current study developed a reliable and rapid test to detect antibodies against the conserved, nonstructural proteins (NSPs) of the FMD virus (FMDV) to distinguish infected animals from vaccinated animals. A monoclonal antibody (MAb) against the FMDV NSP 3B was produced. A competitive enzyme-linked immunosorbent assay (cELISA) for FMDV/NSP antibody detection was developed using a recombinant 3ABC protein as the antigen and the 3B-specific MAb. Sera collected from naive, FMDV experimentally infected, vaccinated carrier, and noncarrier animals were tested using the 3B cELISA. The diagnostic specificity was 99.4% for naive animals (cattle, pigs, and sheep) and 99.7% for vaccinated noncarrier animals. The diagnostic sensitivity was 100% for experimentally inoculated animals and 64% for vaccinated carrier animals. The performance of this 3B cELISA was compared to that of four commercial ELISA kits using a panel of serum samples established by the World Reference Laboratory for FMD at The Pirbright Institute, Pirbright, United Kingdom. The diagnostic sensitivity of the 3B cELISA for the panel of FMDV/NSP-positive bovine serum samples was 94%, which was comparable to or better than that of the commercially available NSP antibody detection kits. This 3B cELISA is a simple, reliable test to detect antibodies against FMDV nonstructural proteins.
Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Identifies Pseudomonas aeruginosa High-Risk Clones
Authors: Cabrolier Nadège , Sauget Marlène , Bertrand Xavier , Hocquet Didier
Published: February 2015

We show here that matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) accurately and quickly identified the five high-risk clones of
Pseudomonas aeruginosa
sequence type 111 (ST111), ST175, ST235, ST253, and ST395. The use of this screening technique by clinical microbiology laboratories may tackle the spread of high-risk clones by the quick implementation of hygiene control procedures for relevant patients.
Comparison of MGIT and Myco/F Lytic Liquid-Based Blood Culture Systems for Recovery of Mycobacterium tuberculosis from Pleural Fluid
Authors: Harausz Elizabeth , Lusiba John Kafuluma , Nsereko Mary , Johnson John L. , Toossi Zahra , Ogwang Sam , Boom W. Henry , Joloba Moses L.
Published: February 2015

The specificities and sensitivities of the Bactec mycobacterial growth indicator tube (MGIT) system for the recovery of
Mycobacterium tuberculosis
from pleural fluid are not statistically different than those of the Myco/F lytic liquid culture system. The time to positivity is shorter in the MGIT system (12.7 versus 20.7 days, respectively;
P
= 0.007). The Myco/F lytic culture system may be an alternative to the MGIT system for diagnosing pleural tuberculosis.
Emergence of an Outbreak-Associated Clostridium difficile Variant with Increased Virulence
Authors: Quesada-Gómez Carlos , López-Ureña Diana , Acuña-Amador Luis , Villalobos-Zúñiga Manuel , Du Tim , Freire Rosemayre , Guzmán-Verri Caterina , Gamboa-Coronado María del Mar , Lawley Trevor D. , Moreno Edgardo , Mulvey Michael R. , Brito Gerly Anne de Castro , Rodríguez-Cavallini Evelyn , Rodríguez César , Chaves-Olarte Esteban
Published: February 2015

The prevalence of
Clostridium difficile
infections has increased due to the emergence of epidemic variants from diverse genetic lineages. Here we describe the emergence of a novel variant during an outbreak in a Costa Rican hospital that was associated with severe clinical presentations. This
C. difficile
variant elicited higher white blood cell counts and caused disease in younger patients than did other strains isolated during the outbreak. Furthermore, it had a recurrence rate, a 30-day attributable disease rate, and disease severity as great as those of the epidemic strain NAP1. Pulsed-field gel electrophoresis genotyping indicated that the outbreak strains belong to a previously undescribed variant, designated NAP
CR1
. Whole-genome sequencing and ribotyping indicated that the NAP
CR1
variant belongs to
C. difficile
ribotype 012 and sequence type 54, as does the reference strain 630. NAP
CR1
strains are resistant to fluoroquinolones due to a mutation in
gyrA
, and they possess an 18-bp deletion in
tcdC
that is characteristic of the epidemic, evolutionarily distinct,
C. difficile
NAP1 variant. NAP
CR1
genomes contain 10% more predicted genes than strain 630, most of which are of hypothetical function and are present on phages and other mobile genetic elements. The increased virulence of NAP
CR1
was confirmed by mortality rates in the hamster model and strong inflammatory responses induced by bacteria-free supernatants in the murine ligated loop model. However, NAP
CR1
strains do not synthesize toxin A and toxin B at levels comparable to those in NAP1 strains. Our results suggest that the pathogenic potential of this emerging
C. difficile
variant is due to the acquisition of hypothetical functions associated with laterally acquired DNA.
Development of a Novel Liquid Bead Array Human Papillomavirus Genotyping Assay (PGMY-LX) and Comparison with Linear Array for Continuity in Longitudinal Cohort Studies
Authors: Farhat Sepideh , Scott Mark E. , Ma Yifei , Moscicki Anna-Barbara
Published: February 2015

Studies of the natural history of human papillomavirus (HPV) infection require reproducible, type-specific testing of the viral types that infect cervical tissue; Linear Array (LA) is one method that has been widely used. We sought to develop a cost-effective, high-throughput alternative using the same PGMY09/11 primer/probe system and offering sensitivity and specificity comparable to those with LA to ensure continuity in longitudinal studies. We report here on a Luminex-based approach, PGMY-LX, that offers type-specific detection of 33 oncogenic and nononcogenic types. Detection of HPV type-specific plasmid DNA was highly specific, with high signal-to-noise ratios for all types except nononcogenic type 40 and no cross-reactivity between types. Cohen's unweighted κ values for 378 clinical samples tested by both LA and PGMY-LX were ≥0.8 (range, 0.80 to 1.0) for 25 types, including oncogenic HPV types 16, 31, 33, 39, 45, 58, and 59 and possibly oncogenic types 53, 66, 73, and 82) and >0.7 (range, 0.74 to 0.79) for oncogenic types 18, 35, 51, and 56 and probable oncogenic type 68b, indicating substantial or better type-specific agreement between the two methods. The reproducibility by PGMY-LX of the types detected by LA varied from 94% when a single HPV type was present to 66% when multiple types were present. The interrun reproducibility for PGMY-LX varied from 98% for single-type infections to 85% for multiple-type infections. The high reproducibility of PGMY-LX and the type-specific agreement with LA allows PGMY-LX to be incorporated into longitudinal, cohort studies that have historically relied on LA.
Recurrence of Disseminated Mycobacterium avium Complex Disease in a Patient with Anti-Gamma Interferon Autoantibodies by Reinfection
Authors: Nishimura Tomoyasu , Fujita-Suzuki Yukiko , Yonemaru Makoto , Ohkusu Kiyofumi , Sakagami Takuro , Carpenter Stephen M. , Otsuka Yoshihito , Namkoong Ho , Yano Ikuya , Hasegawa Naoki
Published: February 2015

We report a case of recurrent disseminated
Mycobacterium avium
complex (DMAC) disease with anti-gamma interferon autoantibodies. To our knowledge, this is the first reported case caused by reinfection with a separate isolate of
M. avium
. DMAC disease activity was monitored using serum IgG antibody titers against lipid antigens extracted from a MAC strain.
Improving the Sensitivity of the Xpert MTB/RIF Assay on Sputum Pellets by Decreasing the Amount of Added Sample Reagent: a Laboratory and Clinical Evaluation
Authors: Dharan Nila J. , Amisano Danielle , Mboowa Gerald , Ssengooba Willy , Blakemore Robert , Kubiak Rachel W. , Armstrong Derek T. , Jones Martin , Manabe Yukari C. , Joloba Moses L. , Ellner Jerrold J. , Dorman Susan E. , Alland David
Published: February 2015

The Xpert MTB/RIF (Xpert) assay permits rapid near-patient detection of
Mycobacterium tuberculosis
in sputum; however, the test sensitivity remains suboptimal in paucibacillary specimens that are negative for acid-fast bacilli using smear microscopy. Xpert testing includes dilution with sample reagent, and when processed sputum pellets are tested, the recommended sample reagent/pellet ratio is 3:1. We evaluated whether a decreased sample reagent/pellet ratio of 2:1 increased Xpert sensitivity compared to the recommended 3:1. The limit of detection was determined by inoculating serial dilutions of
M. tuberculosis
into sputum samples, preparing sputum pellets, and testing each pellet by Xpert at both sample reagent ratios. Processed sputum pellets obtained from
M. tuberculosis
culture-positive clinical specimens were also tested by Xpert at both ratios. Among spiked sputum pellets, the limit of detection was 1,478 CFU/ml (95% confidence interval [CI], 1,211 to 1,943) at a 3:1 ratio and decreased to 832 CFU/ml (95% CI, 671 to 1,134) at 2:1. The proportion of specimens in which
M. tuberculosis
was detected was greater at 2:1 than at 3:1 for almost all numbers of CFU/ml; this difference was most prominent at lower numbers of CFU/ml. Among 134 concentrated sputum pellets from the clinical study, the sensitivity of Xpert at 2:1 was greater than at 3:1 overall (80% versus 72%;
P
= 0.03) and for smear-negative specimens (67% versus 58%;
P
= 0.12). For Xpert testing of sputum pellets, using a lower sample reagent/pellet ratio increased
M. tuberculosis
detection, especially for paucibacillary specimens. Our study supports use of a 2:1 sample reagent/pellet dilution for Xpert testing of sputum pellets.
Cell-Specific Establishment of Poliovirus Resistance to an Inhibitor Targeting a Cellular Protein
Authors: Viktorova Ekaterina G. , Nchoutmboube Jules , Ford-Siltz Lauren A. , Belov George A.
Published: February 2015

It is hypothesized that targeting stable cellular factors involved in viral replication instead of virus-specific proteins may raise the barrier for development of resistant mutants, which is especially important for highly adaptable small (+)RNA viruses. However, contrary to this assumption, the accumulated evidence shows that these viruses easily generate mutants resistant to the inhibitors of cellular proteins at least in some systems. We investigated here the development of poliovirus resistance to brefeldin A (BFA), an inhibitor of the cellular protein GBF1, a guanine nucleotide exchange factor for the small cellular GTPase Arf1. We found that while resistant viruses can be easily selected in HeLa cells, they do not emerge in Vero cells, in spite that in the absence of the drug both cultures support robust virus replication. Our data show that the viral replication is much more resilient to BFA than functioning of the cellular secretory pathway, suggesting that the role of GBF1 in the viral replication is independent of its Arf activating function. We demonstrate that the level of recruitment of GBF1 to the replication complexes limits the establishment and expression of a BFA resistance phenotype in both HeLa and Vero cells. Moreover, the BFA resistance phenotype of poliovirus mutants is also cell type dependent in different cells of human origin and results in a fitness loss in the form of reduced efficiency of RNA replication in the absence of the drug. Thus, a rational approach to the development of host-targeting antivirals may overcome the superior adaptability of (+)RNA viruses.

IMPORTANCE
Compared to the number of viral diseases, the number of available vaccines is miniscule. For some viruses vaccine development has not been successful after multiple attempts, and for many others vaccination is not a viable option. Antiviral drugs are needed for clinical practice and public health emergencies. However, viruses are highly adaptable and can easily generate mutants resistant to practically any compounds targeting viral proteins. An alternative approach is to target stable cellular factors recruited for the virus-specific functions. In the present study, we analyzed the factors permitting and restricting the establishment of the resistance of poliovirus, a small (+)RNA virus, to brefeldin A (BFA), a drug targeting a cellular component of the viral replication complex. We found that the emergence and replication potential of resistant mutants is cell type dependent and that BFA resistance reduces virus fitness. Our data provide a rational approach to the development of antiviral therapeutics targeting host factors.