bluuebunny/crossref_metadata_2025 huggingface dataset:
Updated National Multicenter Registry on Procedural Safety of Catheter Ablation for Atrial Fibrillation
Authors: BERTAGLIA EMANUELE , STABILE GIUSEPPE , PAPPONE ALESSIA , THEMISTOCLAKIS SAKIS , TONDO CLAUDIO , SANCTIS VALERIO DE , SOLDATI EZIO , TRITTO MASSIMO , SOLIMENE FRANCESCO , GRIMALDI MASSIMO , ZOPPO FRANCO , PANDOZI CLAUDIO , AUGELLO GIUSEPPE , CALÒ LEONARDO , PAPPONE CARLO
Published: May 2013

Safety of Catheter Ablation for Atrial Fibrillation

Introduction

Despite catheter ablation (CA) becoming an accepted treatment option for symptomatic, drug‐resistant atrial fibrillation (AF), safety of this procedure continues to be cause for concern. Aim of the present multicenter registry was to assess the incidence of early CA complications and detect their predictors in a contemporary, unselected AF population

Methods and Results

From January 1, 2011 to December 31, 2011, data from 2,323 consecutive patients who underwent CA (median age 60 [52–67]; 72.3% male) for AF in 29 Italian centers were collected. All major complications occurring to the patient from admission to 30th postprocedural day were recorded. No procedure‐related death was observed. Major complications occurred in 94 patients (4.0%): 50 patients (2.2%) suffered vascular access complications; 12 patients (0.5%) developed cardiac tamponade; 14 patients (0.6%) presented with pericarditis; 5 patients (0.2%) had transient ischemic attack; 4 patients had stroke; 3 patients (0.1%) had phrenic nerve paralysis; 3 patients (0.1%) had hemothorax. Other isolated but serious adverse events were documented in 3 patients (0.1%). Female gender (OR 2.643; 95% CI 1.686–4.143; P < 0.0001) and longer procedural duration (OR 2.195; 95% CI 1.388–3.473; P < 0.001) independently predicted a higher risk of complications.

Conclusion

Major complications occurred in 4.0% of the CA procedures for AF, with vascular access complications being the most frequent events.
Stranger danger awareness in Williams syndrome
Authors: Riby D. M. , Kirk H. , Hanley M. , Riby L. M.
Published: May 2013

Background

The developmental disorder Williams syndrome (WS) is characterised by a distinctive cognitive profile and an intriguing social phenotype. Individuals with the disorder are often highly social engaging with familiar and unfamiliar people and once in an interaction they often show subtle abnormalities of social behaviour. Atypically increased approach to unfamiliar people is widely reported in the existing literature for both children and adults. Parents frequently report interactions with unfamiliar people as a major concern.

Methods

In this study we aimed to evaluate ‘stranger danger’ awareness using a video vignette task with individuals who had WS. When linked to other components of the WS phenotype (e.g. reduced intellectual ability, increased social approach) an awareness of stranger danger is particularly important.

Results

Qualitative and quantitative data showed that young people with WS have difficulties making judgements about whether or not to trust and engage in conversation with unfamiliar people. Qualitative data showed that individuals with WS often suggested that they would engage in an interaction with an unfamiliar person.

Conclusions

The findings have substantial implications for the safety of young people with the disorder and emphasise the need for intervention regarding this behaviour.
Pregnancy coexisting with uterus didelphys with a blind hemivagina complicated by pyocolpos due to Pediococcus infection: A case report and review of the published reports
Authors: Park Tae Chul , Lee Hee Joong
Published: May 2013

A woman in early pregnancy was referred due to severe pelvic pain. Vaginal examination showed a severely protruding left vaginal wall with severe tenderness. A transvaginal ultrasound showed a double uterus and a mixed echogenic mass next to the cervix of the left uterus. After creating an opening in the left vaginal wall and inserting a Foley catheter through the opening into the vaginal wall for drainage with antibiotic therapy, the patient's condition rapidly improved. A culture of the pus drained from the vaginal wall showed Pediococcus species. The patient delivered a healthy infant by cesarean section at term gestation without recurrence of pyocolpos. Ten months after delivery, resection of the vaginal septum was performed and the left cervix was exposed. Ultrasound revealed normal kidneys.
They Say Bad Things Come in Threes: How Economic, Political and Cultural Shifts Facilitated Contemporary Anti‐Immigration Activism in the United States
Authors: Ward Matthew
Published: May 2013

This paper, first, provides an analysis of contemporary anti‐immigration activism in the United States, situating it historically and theoretically through an examination of nativism and vigilantism. Second, it merges insights from political process theory and structured ignorance theory to develop an historical account of three key preconditions that set the stage for and accelerated contemporary anti‐immigration activism. In so doing this paper addresses fundamental empirical and theoretical gaps in political process theory and demonstrates how structured ignorance theory can help us better understand how shifting structural conditions promoted contemporary anti‐immigration mobilization by generating perceptions conducive to conservative activism.
Unnatural Narratology: The Systematic Study of Anti‐Mimeticism
Authors: Alber Jan
Published: May 2013

Unnatural narratology is a new field within narrative theory that seeks to focus on the anti‐mimeticism of many fictional narratives. In other words, the research program proposed by unnatural narrative theorists involves the systematic study of the various ways in which fictional narratives deviate from “natural” cognitive frames, i.e., real‐world understandings of time, space, and other human beings. In a second step, unnatural narratologists deal with the interpretative implications or potential functions of such deviations, i.e., the question of what the unnatural might mean or communicate to us. This article focuses on the cognitive branch within unnatural narratology.
Revisiting the Panopticon: professional regulation, surveillance and sousveillance
Authors: Freshwater Dawn , Fisher Pamela , Walsh Elizabeth
Published: May 2013

In this article, we will consider how the regulation of populations is not just a feature of prisons, but of all institutions and organisations that control members though hierarchies, divisions and norms. While nurses and other allied health professionals are considered to be predominantly self‐regulatory, practice is guided by a code of conduct and codes of ethics that act as rules that serve to uphold the safety of the patient, whether they are a sick person in a hospital bed or an inmate in a prison. The codes of conduct espouse a number of rules that to a certain extent govern the behaviour of individual and groups of practitioners through reciprocal rewards and punishments. Supervision is one method of monitoring the effectiveness of the codes of conduct and ethics while regulating both the minimum standard of individual practice and of training organisations. It is posited that one of the possible effects of clinical supervision is to make the person effectively self‐regulatory as, an autonomous practitioner. We take the view that professional autonomy is a highly problematic concept requiring closer examination.
A Simulacrum Account of Dispositional Properties
Authors: Nathan Marco J.
Published: May 2013

This essay presents a model‐theoretic account of dispositional properties, according to which dispositions are not ordinary properties of real entities; dispositions capture the behavior of abstract, idealized models. This account has several payoffs. First, it saves the simple conditional analysis of dispositions. Second, it preserves the general connection between dispositions and regularities, despite the fact that some dispositions are not grounded in actual regularities. Finally, it brings together the analysis and the explanation of dispositions under a unified framework.
Increased vapor pressure deficit due to higher temperature leads to greater transpiration and faster mortality during drought for tree seedlings common to the forest–grassland ecotone
Authors: Will Rodney E. , Wilson Stuart M. , Zou Chris B. , Hennessey Thomas C.
Published: May 2013

Tree species growing along the forest–grassland ecotone are near the moisture limit of their range. Small increases in temperature can increase vapor pressure deficit (VPD) which may increase tree water use and potentially hasten mortality during severe drought.

We tested a 40% increase in VPD due to an increase in growing temperature from 30 to 33°C (constant dewpoint 21°C) on seedlings of 10 tree species common to the forest–grassland ecotone in the southern Great Plains, USA.

Measurement at 33 vs 30°C during reciprocal leaf gas exchange measurements, that is, measurement of all seedlings at both growing temperatures, increased transpiration for seedlings grown at 30°C by 40% and 20% for seedlings grown at 33°C. Higher initial transpiration of seedlings in the 33°C growing temperature treatment resulted in more negative xylem water potentials and fewer days until transpiration decreased after watering was withheld. The seedlings grown at 33°C died 13% (average 2 d) sooner than seedlings grown at 30°C during terminal drought.

If temperature and severity of droughts increase in the future, the forest–grassland ecotone could shift because low seedling survival rate may not sufficiently support forest regeneration and migration.
Cumulative response of ecosystem carbon and nitrogen stocks to chronic CO2 exposure in a subtropical oak woodland
Authors: Hungate Bruce A. , Dijkstra Paul , Wu Zhuoting , Duval Benjamin D. , Day Frank P. , Johnson Dale W. , Megonigal J. Patrick , Brown Alisha L. P. , Garland Jay L.
Published: May 2013

Rising atmospheric carbon dioxide (CO2) could alter the carbon (C) and nitrogen (N) content of ecosystems, yet the magnitude of these effects are not well known. We examined C and N budgets of a subtropical woodland after 11 yr of exposure to elevated CO2.

We used open‐top chambers to manipulate CO2 during regrowth after fire, and measured C, N and tracer 15N in ecosystem components throughout the experiment.

Elevated CO2 increased plant C and tended to increase plant N but did not significantly increase whole‐system C or N. Elevated CO2 increased soil microbial activity and labile soil C, but more slowly cycling soil C pools tended to decline. Recovery of a long‐term 15N tracer indicated that CO2 exposure increased N losses and altered N distribution, with no effect on N inputs.

Increased plant C accrual was accompanied by higher soil microbial activity and increased C losses from soil, yielding no statistically detectable effect of elevated CO2 on net ecosystem C uptake. These findings challenge the treatment of terrestrial ecosystems responses to elevated CO2 in current biogeochemical models, where the effect of elevated CO2 on ecosystem C balance is described as enhanced photosynthesis and plant growth with decomposition as a first‐order response.
The SPLIT Research Agenda 2013
Authors: Alonso Estella M. , Ng Vicky L. , Anand Ravinder , Anderson Christopher D. , Ekong Udeme D. , Fredericks Emily M. , Furuya Katryn N. , Gupta Nitika A. , Lerret Stacee M. , Sundaram Shikha , Tiao Greg ,   Studies of Pediatric Liver Transplantation (SPLIT) Research Group
Published: May 2013

This review focuses on active clinical research in pediatric liver transplantation with special emphasis on areas that could benefit from studies utilizing the SPLIT infrastructure and data repository. Ideas were solicited by members of the SPLIT Research Committee and sections were drafted by members of the committee with expertise in those given areas. This review is intended to highlight priorities for clinical research that could successfully be conducted through the SPLIT collaborative and would have significant impact in pediatric liver transplantation.
Lacan and Social Psychology
Authors: Pavón‐Cuéllar David
Published: May 2013

Jacques Lacan kept silent on the topic of social psychology, never referring to it, not even to criticize it. But this has not impeded Lacanian theory from inspiring diverse critical approaches to social psychology. After reviewing these approaches, the article examines Lacan's different explicit positions with respect to psychology, the social and what he called psychology of the social field. This allows us to infer the implicit manner in which Lacan would establish his silent relationship with social psychology. On the basis of this relationship, we outline an original proposal for a Lacanian critical approach to social psychology that might lead to an alternative transindividual metapsychology. Our proposal precisely differs from others in that it attempts to consider and elucidate Lacan's own attitude regarding social psychology.
Formation of intracratonic basins by lithospheric shortening and phase changes: a case study from the ultra‐deep East Barents Sea basin
Authors: Gac Sébastien , Huismans Ritske S. , Simon Nina S. C. , Podladchikov Yuri Y. , Faleide Jan Inge
Published: May 2013

The origin of large subsidence in intracratonic basins is still under debate. We propose a new and self‐consistent model for the formation of those basins, where lithospheric shortening/buckling triggers metamorphism and densification of crustal mafic heterogeneities. We use a forward thermo‐mechanical finite element technique to evaluate this mechanism for the typical example of the East Barents Sea basin (EBB) where a very large and compensated subsidence, accommodating an up to 20‐km‐thick sediment succession, is observed. The lower crust in the dynamic model is modelled with petrologic‐consistent densities for a wet mafic gabbroic composition that depend on pressure and temperature taking into account dehydration at high PT conditions. The model successfully explains the main characteristics of the EBB, notably the large anomalous and fast subsidence during the Late Permian–Early Triassic, its present‐day geometry and the absence of a significant gravity anomaly.
Seroprevalence of dengue in the general population of Hong Kong
Authors: Lo Constance LH , Yip Shea Ping , Leung Polly HM
Published: May 2013

Objectives

To assess the extent of dengue virus exposure in the population.

Methods

In this seroepidemiological study, 685 blood samples were collected (from April 2007 to July 2009) from two subject groups: (i) 344 samples from anonymous blood donors of the Hong Kong Red Cross and (ii) 341 samples from healthy volunteers recruited from a university, a community centre and a hospital. Demographic information and travel history were collected for the second subject group. All blood samples were subjected to the PanBio Dengue IgG Indirect ELISA.

Results

Anti‐dengue virus IgG was detected in 1.6% of the blood samples. Individuals who visited countries in Southeast Asia in the past year were significantly associated with seropositivity (P = 0.03, OR 5.38, CI 1.13–25.54).

Conclusions

The overall dengue seroprevalence was 1.6%, and visit to Southeast Asia was the only independent predictor for seropositivity. Although the current situation is not alarming, frequent travel, presence of mosquito vector and emergence of local cases suggest that the risk of dengue virus infection within the local community cannot be overlooked, and continuous vigilance is warranted.
Reasons for exclusion of 6820 umbilical cord blood donations in a public cord blood bank
Authors: Wang Tso‐Fu , Wen Shu‐Hui , Yang Kuo‐Liang , Yang Shang‐Hsien , Yang Yun‐Fan , Chang Chu‐Yu , Wu Yi‐Feng , Chen Shu‐Huey
Published: May 2013

Background

To provide information for umbilical cord blood (UCB) banks to adopt optimal collection strategies and to make UCB banks operate efficiently, we investigated the reasons for exclusion of UCB units in a 3‐year recruitment period.

Study Design and Methods

We analyzed records of the reasons for exclusion of the potential UCB donation from 2004 to 2006 in the Tzu‐Chi Cord Blood Bank and compared the results over 3 years. We grouped these reasons for exclusion into five phases, before collection, during delivery, before processing, during processing, and after freezing according to the time sequence and analyzed the reasons at each phase.

Results

Between 2004 and 2006, there were 10,685 deliveries with the intention of UCB donation. In total, 41.2% of the UCB units were considered eligible for transplantation. The exclusion rates were 93.1, 48.4, and 54.1% in 2004, 2005, and 2006, respectively. We excluded 612 donations from women before their child birth, 133 UCB units during delivery, 80 units before processing, 5010 units during processing, and 421 units after freezing. There were 24 UCB units with unknown reasons of ineligibility. Low UCB weight and low cell count were the first two leading causes of exclusion (48.6 and 30.9%). The prevalence of artificial errors, holiday or transportation problem, low weight, and infant problems decreased year after year.

Conclusion

The exclusion rate was high at the beginning of our study as in previous studies. Understanding the reasons for UCB exclusion may help to improve the efficiency of UCB banking programs in the future.
Fundamental Limits in Combine Harvester Header Height Control
Authors: Xie Yangmin , Alleyne Andrew G. , Greer Ashley , Deneault Dustin
Published: May 2013

This paper investigates fundamental performance limitations in the control of a combine harvester's header height control system. There are two primary subsystem characteristics that influence the achievable bandwidth by affecting the open loop transfer function. The first subsystem is the mechanical configuration of the combine and header while the second subsystem is the electrohydraulic actuation for the header. The mechanical combine + header subsystem results in an input–output representation that is underactuated and has a noncollocated sensor/actuator pair. The electrohydraulic subsystem introduces a significant time delay. In combination, they each reinforce the effect of the other thereby exacerbating the overall system limitation of the closed loop bandwidth. Experimental results are provided to validate the model and existence of the closed loop bandwidth limitations that stem from specific system design configurations.
Decentralized Variable Structure Control for Uncertain Large-Scale Time-Delayed Systems: A New Approach
Authors: Gao Cunchen , Zhao Lin
Published: May 2013

In this paper, a novel decentralized variable structure control (DVSC) scheme is proposed for a class of large-scale time-delayed systems (LSSs) with mismatched interconnections and uncertainties. New invariance conditions are derived such that each subsystem in the switching surface is completely invariant to both delay interconnections and uncertainties. It also shows that the stability of each closed-loop subsystem is guaranteed. By constructing auxiliary function and applying matrix norm inequality technique, the developed DVSC law for the interconnected system is realized independently through the delay terms. Moreover, the chattering around the switching surface can be reduced by the proposed design approach. Illustrative example is given to verify the validity of the developed controller.
Prediction of Congestion and Bursting Phenomena in Network Traffic Based on Multifractal Spectrums
Authors: Liu Yan , Liu Li-Guang , Wang Hang
Published: May 2013

From the viewpoint of nonlinear dynamics, a numerical method for predicting the traffic of the local area network (LAN) is presented based on the multifractal spectrums; in particular, for predicting the typical congestion and bursting phenomena, by analyzing real time sequences. First, the multifractal spectrums available to the LAN traffic are derived in some detail and their physical meanings are consequently explained. Then an exponent factor is introduced to the measurement or description of the singularity of the time sequence and the correlations between multifractal spectrums and traffic flow rate are studied in depth. Finally, as an example, the multifractal spectrums presented are used to predict the network traffic of an Ethernet by analyzing its real time sequence. The results show that there exists a distinct relationship between the multifractal spectrums and the traffic flow rate of networks and the multifractal spectrum could be used to efficiently and feasibly predict the traffic flow rate, especially for predicting the singularities of the real time sequences, which are closely related to the congestion and bursting phenomena. Thus, this method can be applied to the prediction and management of the congestion and bursting in the network traffic at an early time. Furthermore, the prediction will become much more accurate and powerful over a long period, since the fluctuations of the traffic flow rate are remarkable.
Vibration of a Temperature-Dependent Thermally Pre/Postbuckled FGM Beam Over a Nonlinear Hardening Elastic Foundation
Authors: Esfahani S. E. , Kiani Y. , Komijani M. , Eslami M. R.
Published: May 2013

Small amplitude vibrations of a functionally graded material beam under in-plane thermal loading in the prebuckling and postbuckling regimes is studied in this paper. The material properties of the FGM media are considered as function of both position and temperature. A three parameters elastic foundation including the linear and nonlinear Winkler springs along with the Pasternak shear layer is in contact with beam in deformation, which acts in tension as well as in compression. The solution is sought in two regimes. The first one, a static phase with large amplitude response, and the second one, a dynamic regime near the static one with small amplitude. In both regimes, nonlinear governing equations are discretized using the generalized differential quadrature (GDQ) method and solved iteratively via the Newton–Raphson method. It is concluded that depending on the type of boundary condition and loading type, free vibration of a beam under in-plane thermal loading may reach zero at a certain temperature which indicates the existence of bifurcation type of instability.
A Theory of Flexoelectric Membranes and Effective Properties of Heterogeneous Membranes
Authors: Mohammadi P. , Liu L. P. , Sharma P.
Published: May 2013

Recent developments in flexoelectricity, especially in nanostructures, have lead to several interesting notions such as piezoelectric materials without using piezoelectric materials and enhanced energy harvesting at the nanoscale, among others. In the biological context also, membrane flexoelectricity has been hypothesized to play an important role, e.g., biological mechanotransduction and hearing mechanisms, among others. In this paper, we consider a heterogeneous flexoelectric membrane and derive the homogenized or renormalized flexoelectric, dielectric, and elastic response, therefore, relating the corresponding effective electromechanical properties to its microstructural details. Our work allows design of a microstructure to tailor flexoelectric response, and an illustrative example is given for biological membranes.
Acoustic Radiation of a Cylindrical Piezoelectric Power Transformer
Authors: Zhang He , Ye Guiru , Zhang Zhicheng
Published: May 2013

Theoretical analysis is performed for the sound radiation of a cylindrical power transformer composed of piezoelectric transducers with radial polarization. The transformer is driven in thickness-stretch mode, and an exact solution is obtained for the sound pressure and sound power level in the surrounding fluid. Representative examples are used to illustrate the sound field induced by the operation of the transformer. Numerical results indicate that the electrical impedance and the thickness ratio of actuator/sensor to metal core have considerable effects on sound radiation of the cylindrical power transformer.
The Impact of Return Orifices on the Stability of a Four-Way Valve–Controlled Double-Acting Actuator
Authors: Zhang Shusen
Published: May 2013

This paper studies the influence of the return and the valve spring rate on the stability of a four-way valve–controlled double-acting actuator. A fully nonlinear model for this system is developed based on the orifice equation. The new model contains both the upstream chamber and downstream chamber for each orifice. The geometry of the return orifice and the valve spring rate has an impact on the stability boundary of the four-way valve–controlled double-acting actuator. A larger return orifice requires using a stronger valve spring to ensure the stability of the system. It is shown that, for the nonlinear system, a stable limit circle can be born from an unstable origin as bifurcation occurs.
Fluid-Structure Interaction Modeling of Abdominal Aortic Aneurysms: The Impact of Patient-Specific Inflow Conditions and Fluid/Solid Coupling
Authors: Chandra Santanu , Raut Samarth S. , Jana Anirban , Biederman Robert W. , Doyle Mark , Muluk Satish C. , Finol Ender A.
Published: May 2013

Rupture risk assessment of abdominal aortic aneurysms (AAA) by means of biomechanical analysis is a viable alternative to the traditional clinical practice of using a critical diameter for recommending elective repair. However, an accurate prediction of biomechanical parameters, such as mechanical stress, strain, and shear stress, is possible if the AAA models and boundary conditions are truly patient specific. In this work, we present a complete fluid-structure interaction (FSI) framework for patient-specific AAA passive mechanics assessment that utilizes individualized inflow and outflow boundary conditions. The purpose of the study is two-fold: (1) to develop a novel semiautomated methodology that derives velocity components from phase-contrast magnetic resonance images (PC-MRI) in the infrarenal aorta and successfully apply it as an inflow boundary condition for a patient-specific fully coupled FSI analysis and (2) to apply a one-way–coupled FSI analysis and test its efficiency compared to transient computational solid stress and fully coupled FSI analyses for the estimation of AAA biomechanical parameters. For a fully coupled FSI simulation, our results indicate that an inlet velocity profile modeled with three patient-specific velocity components and a velocity profile modeled with only the axial velocity component yield nearly identical maximum principal stress (σ1), maximum principal strain (ε1), and wall shear stress (WSS) distributions. An inlet Womersley velocity profile leads to a 5% difference in peak σ1, 3% in peak ε1, and 14% in peak WSS compared to the three-component inlet velocity profile in the fully coupled FSI analysis. The peak wall stress and strain were found to be in phase with the systolic inlet flow rate, therefore indicating the necessity to capture the patient-specific hemodynamics by means of FSI modeling. The proposed one-way–coupled FSI approach showed potential for reasonably accurate biomechanical assessment with less computational effort, leading to differences in peak σ1, ε1, and WSS of 14%, 4%, and 18%, respectively, compared to the axial component inlet velocity profile in the fully coupled FSI analysis. The transient computational solid stress approach yielded significantly higher differences in these parameters and is not recommended for accurate assessment of AAA wall passive mechanics. This work demonstrates the influence of the flow dynamics resulting from patient-specific inflow boundary conditions on AAA biomechanical assessment and describes methods to evaluate it through fully coupled and one-way–coupled fluid-structure interaction analysis.
Role of Cells in Freezing-Induced Cell-Fluid-Matrix Interactions Within Engineered Tissues
Authors: Seawright Angela , Ozcelikkale Altug , Dutton Craig , Han Bumsoo
Published: May 2013

During cryopreservation, ice forms in the extracellular space resulting in freezing-induced deformation of the tissue, which can be detrimental to the extracellular matrix (ECM) microstructure. Meanwhile, cells dehydrate through an osmotically driven process as the intracellular water is transported to the extracellular space, increasing the volume of fluid for freezing. Therefore, this study examines the effects of cellular presence on tissue deformation and investigates the significance of intracellular water transport and cell-ECM interactions in freezing-induced cell-fluid-matrix interactions. Freezing-induced deformation characteristics were examined through cell image deformetry (CID) measurements of collagenous engineered tissues embedded with different concentrations of MCF7 breast cancer cells versus microspheres as their osmotically inactive counterparts. Additionally, the development of a biophysical model relates the freezing-induced expansion of the tissue due to the cellular water transport and the extracellular freezing thermodynamics for further verification. The magnitude of the freezing-induced dilatation was found to be not affected by the cellular water transport for the cell concentrations considered; however, the deformation patterns for different cell concentrations were different suggesting that cell-matrix interactions may have an effect. It was, therefore, determined that intracellular water transport during freezing was insignificant at the current experimental cell concentrations; however, it may be significant at concentrations similar to native tissue. Finally, the cell-matrix interactions provided mechanical support on the ECM to minimize the expansion regions in the tissues during freezing.
Students as Collaborators in Systems Biology Research
Authors: McClatchy Susan , McGann Deborah , Gotwals Robert , Baskett Amanda , Churchill Gary
Published: May 2013

Quantitative Trait Mapping, an IBI prize–winning module, immerses students in the role of a systems biology researcher.
Functional Extinction of Birds Drives Rapid Evolutionary Changes in Seed Size
Authors: Galetti Mauro , Guevara Roger , Côrtes Marina C. , Fadini Rodrigo , Von Matter Sandro , Leite Abraão B. , Labecca Fábio , Ribeiro Thiago , Carvalho Carolina S. , Collevatti Rosane G. , Pires Mathias M. , Guimarães Paulo R. , Brancalion Pedro H. , Ribeiro Milton C. , Jordano Pedro
Published: May 2013

The Birds and the Seeds

When species are lost from ecosystems through local extinction, the pattern of ecological interactions changes.Galettiet al.(p.1086) show how the loss of large fruit-eating birds from tropical forest fragments in Brazil affects the reduction of seed size in a palm species. A data set was compiled that consisted of >9000 seeds measured in 22 populations over a large area of Atlantic rainforest, including seven areas where large-seed dispersers (toucans, cracids, and large cotingas) were extinct and 15 areas where they are still common.
Neuronal Birth to Cortical Circuitry
Authors: Anderson Stewart , Coulter Douglas
Published: May 2013

Developmental genetics of single neuron populations can reveal how cortical circuits are built and how neuropsychiatric diseases arise.
Measurements of Energetic Particle Radiation in Transit to Mars on the Mars Science Laboratory
Authors: Zeitlin C. , Hassler D. M. , Cucinotta F. A. , Ehresmann B. , Wimmer-Schweingruber R. F. , Brinza D. E. , Kang S. , Weigle G. , Böttcher S. , Böhm E. , Burmeister S. , Guo J. , Köhler J. , Martin C. , Posner A. , Rafkin S. , Reitz G.
Published: May 2013

Going to Mars

The Mars Science Laboratory spacecraft containing the Curiosity rover, was launched from Earth in November 2011 and arrived at Gale crater on Mars in August 2012.

Zeitlin
et al.

(p.
1080
) report measurements of the energetic particle radiation environment inside the spacecraft during its cruise to Mars, confirming the hazard likely to be posed by this radiation to astronauts on a future potential trip to Mars.

Williams
et al.

(p.
1068
, see the Perspective by

Jerolmack

) report the detection of sedimentary conglomerates (pebbles mixed with sand and turned to rock) at Gale crater. The rounding of the rocks suggests abrasion of the pebbles as they were transported by flowing water several kilometers or more from their source.
Enantio- and Diastereodivergent Dual Catalysis: α-Allylation of Branched Aldehydes
Authors: Krautwald Simon , Sarlah David , Schafroth Michael A. , Carreira Erick M.
Published: May 2013

Independent Chiral Catalysts

Synthetic catalysts can be prepared in their mirror-image form and thereby furnish the mirror-image (enantiomer) of the reaction product. In practice, however, this versatility is largely limited to products featuring a single stereocenter that accounts for the dissymmetry.

Krautwald
et al.

(p.
1065
; see the Perspective by

Schindler and Jacobsen

) now report a pair of chiral catalysts—an iridium complex and an amine—that operate in concert to facilitate carbon-carbon bond formation, while retaining independent stereoselectivity toward their respective sides of the bond.
Echinocandin and Triazole Antifungal Susceptibility Profiles for Clinical Opportunistic Yeast and Mold Isolates Collected from 2010 to 2011: Application of New CLSI Clinical Breakpoints and Epidemiological Cutoff Values for Characterization of Geographic and Temporal Trends of Antifungal Resistance
Authors: Pfaller Michael A. , Messer Shawn A. , Woosley Leah N. , Jones Ronald N. , Castanheira Mariana
Published: May 2013

The SENTRY Antimicrobial Surveillance Program monitors global susceptibility and resistance rates of newer and established antifungal agents. We report the echinocandin and triazole antifungal susceptibility patterns for 3,418 contemporary clinical isolates of yeasts and molds. The isolates were obtained from 98 laboratories in 34 countries during 2010 and 2011. Yeasts not presumptively identified by CHROMagar, the trehalose test, or growth at 42°C and all molds were sequence identified using internal transcribed spacer (ITS) and 28S (yeasts) or ITS, translation elongation factor (TEF), and 28S (molds) genes. Susceptibility testing was performed against 7 antifungals (anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole) using CLSI methods. Rates of resistance to all agents were determined using the new CLSI clinical breakpoints and epidemiological cutoff value criteria, as appropriate. Sequencing of
fks
hot spots was performed for echinocandin non-wild-type (WT) strains. Isolates included 3,107 from 21
Candida
spp., 146 from 9
Aspergillus
spp., 84 from
Cryptococcus neoformans
, 40 from 23 other mold species, and 41 from 9 other yeast species. Among
Candida
spp., resistance to the echinocandins was low (0.0 to 1.7%).
Candida albicans
and
Candida glabrata
that were resistant to anidulafungin, caspofungin, or micafungin were shown to have
fks
mutations. Resistance to fluconazole was low among the isolates of
C. albicans
(0.4%),
Candida tropicalis
(1.3%), and
Candida parapsilosis
(2.1%); however, 8.8% of
C. glabrata
isolates were resistant to fluconazole. Among echinocandin-resistant
C. glabrata
isolates from 2011, 38% were fluconazole resistant. Voriconazole was active against all
Candida
spp. except
C. glabrata
(10.5% non-WT), whereas posaconazole showed decreased activity against
C. albicans
(4.4%) and
Candida krusei
(15.2% non-WT). All agents except for the echinocandins were active against
C. neoformans
, and the triazoles were active against other yeasts (MIC
90
, 2 μg/ml). The echinocandins and triazoles were active against
Aspergillus
spp. (MIC
90
/minimum effective concentration [MEC
90
] range, 0.015 to 2 μg/ml), but the echinocandins were not active against other molds (MEC
90
range, 4 to >16 μg/ml). Overall, echinocandin and triazole resistance rates were low; however, the fluconazole and echinocandin coresistance among
C. glabrata
strains warrants continued close surveillance.
Use of Vitek 2 Antimicrobial Susceptibility Profile To Identify
mecC
in Methicillin-Resistant Staphylococcus aureus
Authors: Cartwright Edward J. P. , Paterson Gavin K. , Raven Kathy E. , Harrison Ewan M. , Gouliouris Theodore , Kearns Angela , Pichon Bruno , Edwards Giles , Skov Robert L. , Larsen Anders R. , Holmes Mark A. , Parkhill Julian , Peacock Sharon J. , Török M. Estée
Published: May 2013

The emergence of
mecC
methicillin-resistant
Staphylococcus aureus
(MRSA) poses a diagnostic challenge for clinical microbiology laboratories. Using the Vitek 2 system, we tested a panel of 896
Staphylococcus aureus
isolates and found that an oxacillin-sensitive/cefoxitin-resistant profile had a sensitivity of 88.7% and a specificity of 99.5% for the identification of
mecC
MRSA isolates. The presence of the
mecC
gene, determined by bacterial whole-genome sequencing, was used as the gold standard. This profile could provide a zero-cost screening method for identification of
mecC
-positive MRSA strains.
Lipid Raft- and Src Family Kinase-Dependent Entry of Coxsackievirus B into Human Placental Trophoblasts
Authors: Delorme-Axford Elizabeth , Sadovsky Yoel , Coyne Carolyn B.
Published: May 2013

Maternal-fetal transmission of group B coxsackieviruses (CVB) during pregnancy has been associated with a number of diverse pathological outcomes, including hydrops fetalis, fetal myocarditis, meningoencephalitis, neurodevelopmental delays, congenital skin lesions, miscarriage, and/or stillbirth. Throughout pregnancy, the placenta forms a critical antimicrobial protective barrier at the maternal-fetal interface. Despite the severity of diseases accompanying fetal CVB infections, little is known regarding the strategies used by CVB to gain entry into placental trophoblasts. Here we used both a trophoblast cell line and primary human trophoblasts to demonstrate the mechanism by which CVB gains entry into polarized placental trophoblasts. Our studies revealed that the kinetics of CVB entry into placental trophoblasts are similar to those previously described for polarized intestinal epithelial cells. Likewise, CVB entry into placental trophoblasts requires decay-accelerating factor (DAF) binding and involves relocalization of the virus from the apical surface to intercellular tight junctions. In contrast, we have identified a divergent mechanism for CVB entry into polarized trophoblasts that is clathrin, caveolin-1, and dynamin II independent but requires intact lipid rafts. In addition, we found that members of the Src family of tyrosine kinases were required for CVB entry. Our studies highlight the complexity of viral entry into human placental trophoblasts and may serve as a model for mechanisms used by diverse pathogens to penetrate the placental barrier.
Antibody and Antiretroviral Preexposure Prophylaxis Prevent Cervicovaginal HIV-1 Infection in a Transgenic Mouse Model
Authors: Gruell Henning , Bournazos Stylianos , Ravetch Jeffrey V. , Ploss Alexander , Nussenzweig Michel C. , Pietzsch John
Published: May 2013

The development of an effective vaccine preventing HIV-1 infection remains elusive. Thus, the development of novel approaches capable of preventing HIV-1 transmission is of paramount importance. However, this is partly hindered by the lack of an easily accessible small-animal model to rapidly measure viral entry. Here, we report the generation of a human CD4- and human CCR5-expressing transgenic luciferase reporter mouse that facilitates measurement of peritoneal and genitomucosal HIV-1 pseudovirus entry
in vivo
. We show that antibodies and antiretrovirals mediate preexposure protection in this mouse model and that the serum antibody concentration required for protection from cervicovaginal infection is comparable to that required to protect macaques. Our results suggest that this system represents a model for the preclinical evaluation of prophylactic or vaccine candidates. It further supports the idea that broadly neutralizing antibodies should be evaluated for use as preexposure prophylaxis in clinical trials.
Natural Variation in the Heparan Sulfate Binding Domain of the Eastern Equine Encephalitis Virus E2 Glycoprotein Alters Interactions with Cell Surfaces and Virulence in Mice
Authors: Gardner Christina L. , Choi-Nurvitadhi Jo , Sun Chengqun , Bayer Avraham , Hritz Jozef , Ryman Kate D. , Klimstra William B.
Published: May 2013

Recently, we compared amino acid sequences of the E2 glycoprotein of natural North American eastern equine encephalitis virus (NA-EEEV) isolates and demonstrated that naturally circulating viruses interact with heparan sulfate (HS) and that this interaction contributes to the extreme neurovirulence of EEEV (C. L. Gardner, G. D. Ebel, K. D. Ryman, and W. B. Klimstra, Proc. Natl. Acad. Sci. U. S. A., 108:16026–16031, 2011). In the current study, we have examined the contribution to HS binding of each of three lysine residues in the E2 71-to-77 region that comprise the primary HS binding site of wild-type (WT) NA-EEEV viruses. We also report that the original sequence comparison identified five virus isolates, each with one of three amino acid differences in the E2 71-to-77 region, including mutations in residues critical for HS binding by the WT virus. The natural variant viruses, which possessed either a mutation from lysine to glutamine at E2 71, a mutation from lysine to threonine at E2 71, or a mutation from threonine to lysine at E2 72, exhibited altered interactions with heparan sulfate and cell surfaces and altered virulence in a mouse model of EEEV disease. An electrostatic map of the EEEV E1/E2 heterotrimer based upon the recent Chikungunya virus crystal structure (J. E. Voss, M. C. Vaney, S. Duquerroy, C. Vonrhein, C. Girard-Blanc, E. Crublet, A. Thompson, G. Bricogne, and F. A. Rey, Nature, 468:709–712, 2010) showed the HS binding site to be at the apical surface of E2, with variants affecting the electrochemical nature of the binding site. Together, these results suggest that natural variation in the EEEV HS binding domain may arise during EEEV sylvatic cycles and that this variation may influence receptor interaction and the severity of EEEV disease.
Cytomegalovirus UL91 Is Essential for Transcription of Viral True Late (γ2) Genes
Authors: Omoto Shinya , Mocarski Edward S.
Published: May 2013

Human cytomegalovirus-encoded UL91 is a betagamma gene that is essential for viral replication. Here we show that the 111-amino-acid (aa) UL91 protein controls accumulation of true-late (γ2) viral transcripts. The primate betaherpesvirus conserved N-terminal region from aa 1 to 71 is sufficient to fully reconstitute function. Evaluation of viral DNA, RNA, and antigen revealed that UL91 protein is expressed with leaky-late (γ1) kinetics, localizes in the nucleus without influencing viral DNA synthesis, and must be present from 48 h postinfection to support full expression of late viral transcripts and proteins. In the absence of UL91, viral capsid assembly in the nucleus of infected cells is significantly reduced, and mature, cytoplasmic virions fail to form. Taken together, the evidence shows that UL91 regulates late viral gene expression by a mechanism that is apparently conserved in betaherpesviruses and gammaherpesviruses.
Genetic Characterization of Betacoronavirus Lineage C Viruses in Bats Reveals Marked Sequence Divergence in the Spike Protein of Pipistrellus Bat Coronavirus HKU5 in Japanese Pipistrelle: Implications for the Origin of the Novel Middle East Respiratory Syndrome Coronavirus
Authors: Lau Susanna K. P. , Li Kenneth S. M. , Tsang Alan K. L. , Lam Carol S. F. , Ahmed Shakeel , Chen Honglin , Chan Kwok-Hung , Woo Patrick C. Y. , Yuen Kwok-Yung
Published: May 2013

While the novel Middle East respiratory syndrome coronavirus (MERS-CoV) is closely related to
Tylonycteris
bat CoV HKU4 (Ty-BatCoV HKU4) and
Pipistrellus
bat CoV HKU5 (Pi-BatCoV HKU5) in bats from Hong Kong, and other potential lineage C betacoronaviruses in bats from Africa, Europe, and America, its animal origin remains obscure. To better understand the role of bats in its origin, we examined the molecular epidemiology and evolution of lineage C betacoronaviruses among bats. Ty-BatCoV HKU4 and Pi-BatCoV HKU5 were detected in 29% and 25% of alimentary samples from lesser bamboo bat (
Tylonycteris pachypus
) and Japanese pipistrelle (
Pipistrellus abramus
), respectively. Sequencing of their RNA polymerase (RdRp), spike (S), and nucleocapsid (N) genes revealed that MERS-CoV is more closely related to Pi-BatCoV HKU5 in RdRp (92.1% to 92.3% amino acid [aa] identity) but is more closely related to Ty-BatCoV HKU4 in S (66.8% to 67.4% aa identity) and N (71.9% to 72.3% aa identity). Although both viruses were under purifying selection, the S of Pi-BatCoV HKU5 displayed marked sequence polymorphisms and more positively selected sites than that of Ty-BatCoV HKU4, suggesting that Pi-BatCoV HKU5 may generate variants to occupy new ecological niches along with its host in diverse habitats. Molecular clock analysis showed that they diverged from a common ancestor with MERS-CoV at least several centuries ago. Although MERS-CoV may have diverged from potential lineage C betacoronaviruses in European bats more recently, these bat viruses were unlikely to be the direct ancestor of MERS-CoV. Intensive surveillance for lineage C betaCoVs in
Pipistrellus
and related bats with diverse habitats and other animals in the Middle East may fill the evolutionary gap.
High-Throughput Sequencing Reveals Principles of Adeno-Associated Virus Serotype 2 Integration
Authors: Janovitz Tyler , Klein Isaac A. , Oliveira Thiago , Mukherjee Piali , Nussenzweig Michel C. , Sadelain Michel , Falck-Pedersen Erik
Published: May 2013

Viral integrations are important in human biology, yet genome-wide integration profiles have not been determined for many viruses. Adeno-associated virus (AAV) infects most of the human population and is a prevalent gene therapy vector. AAV integrates into the human genome with preference for a single locus, termed AAVS1. However, the genome-wide integration of AAV has not been defined, and the principles underlying this recombination remain unclear. Using a novel high-throughput approach, integrant capture sequencing, nearly 12 million AAV junctions were recovered from a human cell line, providing five orders of magnitude more data than were previously available. Forty-five percent of integrations occurred near AAVS1, and several thousand novel integration hotspots were identified computationally. Most of these occurred in genes, with dozens of hotspots targeting known oncogenes. Viral replication protein binding sites (RBS) and transcriptional activity were major factors favoring integration. In a first for eukaryotic viruses, the data reveal a unique asymmetric integration profile with distinctive directional orientation of viral genomes. These studies provide a new understanding of AAV integration biology through the use of unbiased high-throughput data acquisition and bioinformatics.
Characterizing durability of mudrocks for slope stability purposes
Authors: Dick Jeffrey C. , Shakoor Abdul
Published: May 2013

The lithologic characteristics and slake durability of mudrocks from 48 natural and human-made slopes were investigated with the objective of developing a classification of mudrock durability for slope stability purposes. Slopes from which samples were taken ranged from long-term stable to highly unstable. Samples included 10 claystones, 17 shales, and 21 mudstones. The durability of mudrocks was classified as high, medium, or low on the basis of relationships between lithologic characteristics, slake durability, and slope conditions, as observed in the field. The three classes of durability were then used to evaluate the likelihood of occurrence of the four commonly recognized types of instability that affect slopes in mudrocks: excessive erosion, slumps, debris flows, and undercutting-induced failures. High-durability mudrocks were found to be susceptible to undercutting only, medium-durability mudrocks to slumps, debris flows, and undercutting-induced failures, and low-durability mudrocks to all four types of slope instability.