bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Mechanical Properties of Fused Deposition Modeling-Manufactured Parts Through Build Parameter Modifications
Authors: Shojib Hossain Mohammad , Espalin David , Ramos Jorge , Perez Mireya , Wicker Ryan
Published: September 2014

Today, the use of material extrusion processes, like fused deposition modeling (FDM), in aerospace, biomedical science, and other industries, is gaining popularity because of the access to production-grade thermoplastic polymer materials. This paper focuses on how modifying process parameters such as build orientation, raster angle (RA), contour width (CW), raster width (RW), and raster-to-raster air gap (RRAG) can improve ultimate tensile strength (UTS), Young's modulus, and tensile strain. This was assessed using three methods: default, Insight revision, and visual feedback. On average, parameter modification through the visual feedback method improved UTS in all orientations, 16% in XYZ, 7% in XZY, and 22% in ZXY.
A Review on Process Monitoring and Control in Metal-Based Additive Manufacturing
Authors: Tapia Gustavo , Elwany Alaa
Published: September 2014

There is consensus among both the research and industrial communities, and even the general public, that additive manufacturing (AM) processes capable of processing metallic materials are a set of game changing technologies that offer unique capabilities with tremendous application potential that cannot be matched by traditional manufacturing technologies. Unfortunately, with all what AM has to offer, the quality and repeatability of metal parts still hamper significantly their widespread as viable manufacturing processes. This is particularly true in industrial sectors with stringent requirements on part quality such as the aerospace and healthcare sectors. One approach to overcome this challenge that has recently been receiving increasing attention is process monitoring and real-time process control to enhance part quality and repeatability. This has been addressed by numerous research efforts in the past decade and continues to be identified as a high priority research goal. In this review paper, we fill an important gap in the literature represented by the absence of one single source that comprehensively describes what has been achieved and provides insight on what still needs to be achieved in the field of process monitoring and control for metal-based AM processes.
Development of Freeze-Form Extrusion Fabrication With Use of Sacrificial Material
Authors: Leu Ming C. , Garcia Diego A.
Published: September 2014

The development of freeze-form extrusion fabrication (FEF) process to fabricate three-dimensional (3D) ceramic parts with use of sacrificial material to build support sections during the fabrication process is presented in this paper. FEF is an environmentally friendly, additive manufacturing (AM) process that builds 3D parts in a freezing environment layer-by-layer by computer controlled extrusion and deposition of aqueous colloidal pastes based on computer-aided design (CAD) models. Methyl cellulose was identified as the support material, and alumina was used as the main material in this study. After characterizing the dynamics of extruding alumina and methyl cellulose pastes, a general tracking controller (GTC) was developed and applied to control the extrusion force in depositing both alumina and methyl cellulose pastes. The controller was able to reduce the time constant of the closed-loop system by more than 65% in comparison to the open-loop control system. Freeze-drying was used to remove the water content after the part has been built. The support material was then removed in the binder burnout process. Finally, sintering was done to densify the ceramic part. The fabrication of a cube-shaped part with a square hole in each side that requires depositing the sacrificial material during the FEF process was demonstrated.
Development and Integration of Rain Ingestion Effects in Engine Performance Simulations
Authors: Roumeliotis I. , Alexiou A. , Aretakis N. , Sieros G. , Mathioudakis K.
Published: September 2014

Rain ingestion can significantly affect the performance and operability of gas turbine aero-engines. In order to study and understand rain ingestion phenomena at engine level, a performance model is required that integrates component models capable of simulating the physics of rain ingestion. The current work provides, for the first time in the open literature, information about the setup of a mixed-fidelity engine model suitable for rain ingestion simulation and corresponding overall engine performance results. Such a model can initially support an analysis of rain ingestion during the predesign phase of engine development. Once components and engine models are validated and calibrated versus experimental data, they can then be used to support certification tests, the extrapolation of ground test results to altitude conditions, the evaluation of control or engine hardware improvements and eventually the investigation of in-flight events. In the present paper, component models of various levels of fidelity are first described. These models account for the scoop effect at engine inlet, the fan effect and the effects of water presence in the operation and performance of the compressors and the combustor. Phenomena such as velocity slip between the liquid and gaseous phases, droplet breakup, droplet–surface interaction, droplet and film evaporation as well as compressor stages rematching due to evaporation are included in the calculations. Water ingestion influences the operation of the components and their matching, so in order to simulate rain ingestion at engine level, a suitable multifidelity engine model has been developed in the Proosis simulation platform. The engine model's architecture is discussed, and a generic high bypass turbofan is selected as a demonstration test case engine. The analysis of rain ingestion effects on engine performance and operability is performed for the worst case scenario, with respect to the water quantity entering the engine. The results indicate that rain ingestion has a strong negative effect on high-pressure compressor surge margin, fuel consumption, and combustor efficiency, while more than half of the water entering the core is expected to remain unevaporated and reach the combustor in the form of film.
Experimental Analysis on Adsorption Characteristics of Methanol and R134A by Activated Carbon in Adsorption Refrigeration System
Authors: Baiju V. , Muraleedharan C.
Published: September 2014

This paper presents adsorption and desorption characteristics of two different working pairs—activated carbon–methanol and activated carbon–R134a—determined experimentally. Dubinin–Radushkevich (D–R) equation is used to correlate the adsorption isotherms and to form the pressure, temperature, and concentration diagrams for both the assorted working pairs. The results show that the maximum adsorption capacity of activated carbon–R134a working pair is 1.21 times that of activated carbon–methanol. Temperature and pressure distribution throughout the adsorbent bed and their variation with adsorption time are also predicted. Use of artificial neural network (ANN) is proposed to determine the uptake from measured pressure and temperature. The back propagation algorithm with three different variants, namely, scaled conjugate gradient (SCG), Pola–Ribiere conjugate gradient (CGP), and Levenberg–Marquardt (LM) and logistic sigmoid transfer function are used, so that the best approach could be found out. After training, it is found that LM algorithm with 11 neurons is the most suitable for modeling adsorption refrigeration system. The adsorption and desorption uptake obtained experimentally are compared with the uptake predicted by D–R equation and ANN modeling.
Analysis of a Bow-Free Prestressed Test Specimen
Authors: Suhir E. , Nicolics J.
Published: September 2014

Broadening the temperature range in accelerated testing of electronic products is a typical measure to assure that the product of interest is sufficiently robust. At the same time, a too broad temperature range can lead to the shift in the modes and mechanisms of failure, i.e., result in failures that will not occur in actual operation conditions. Application of mechanical prestressing of the test specimen could be an effective means for narrowing the temperature range during accelerated testing and thereby achieving trustworthy and failure-mode-shift-free accelerated test information. Accordingly, simple engineering predictive models are developed for the evaluation of the magnitude and the distribution of thermal and mechanical stresses in a prestressed bow-free test specimen. A design, in which an electronic or a photonic package is bonded between two identical substrates, is considered. Such a design is often employed in some today's packaging systems, in which the “inner,” functional, component containing active and/or passive devices and interconnects is placed between two identical “outer” components (substrates). The addressed stresses include normal stresses acting in the component cross sections and the interfacial shearing and peeling stresses. Although the specimen as a whole remains bow-free, the peeling stresses might be nevertheless appreciable, since the outer components, if thin enough, deflect to a greater or lesser extent with respect to the inner component. The numerical example has indicated that the maxima of the interfacial thermal shearing and peeling stresses are indeed comparable and that these maxima are on the same order of magnitude as the normal thermal stresses acting in the components' cross sections. It is shown that since the thermal and the prestressing mechanical loads are of different physical nature, the stresses caused by these two load categories are distributed differently over the specimen's length. It is shown also that although it is possible and even advisable to apply mechanical prestressing for a lower temperature range, it is impossible to reproduce the same stress distribution as in the case of thermal loading. The obtained results enable one to shed light on the physics of the state of stress in prestressed bow-free test specimens in electronics and photonics engineering.
Electrical behavior of atomic layer deposited high quality SiO2 gate dielectric
Authors: Pradhan Sangram K. , Tanyi Ekembu K. , Skuza Jonathan R. , Xiao Bo , Pradhan Aswini K.
Published: September 2014

Comprehensive and systematic electrical studies were performed on fabrication of high quality SiO2 thin films MOS capacitor using the robust, novel, and simple atomic layer deposition (ALD) technique using highly reactive ozone and tris (dimethylamino) silane (TDMAS) precursors. Ideal capacitance–voltage curve exhibits a very small frequency dispersion and hysteresis behavior of the SiO2 MOS capacitor grown at 1 s TDMAS pulse, suggesting excellent interfacial quality and purity of the film as probed using x-ray photoelectron studies. The flat-band voltage of the device shifted from negative toward positive voltage axis with increase of TDMAS pulses from 0.2 to 2 s. Based on an equivalent oxide thickness point of view, all SiO2 films have gate leakage current density of (5.18 × 10−8 A/cm2) as well as high dielectric break down fields of more than (∼10 MV/cm), which is better and comparable to that of thermally grown SiO2 at temperatures above 800 °C. These appealing electrical properties of ALD grown SiO2 thin films enable its potential applications such as high-quality gate insulators for thin film MOS transistors, as well as insulators for sensor and nanostructures on nonsilicon substrates.

At the request of the authors, this article is being retracted effective 27 December 2014.
On the appearance of vorticity and gradient shear bands in wormlike micellar solutions of different CPCl/salt systems
Authors: Mütze Annekathrin , Heunemann Peggy , Fischer Peter
Published: September 2014

Wormlike micellar salt/surfactant solutions (X-salicylate, cetylpyridinium chloride) are studied with respect to the applied shear stress, concentration, temperature, and composition of the counterions (X = lithium, sodium, potassium, magnesium, and calcium) of the salicylate salt solute to determine vorticity and gradient shear bands. A combination of rheological measurements, laser technique, video analysis, and rheo-small-angle neutron scattering allow for a detailed exploration of number and types of shear bands. Typical flow curves of the solutions show Newtonian, shear-thinning, and shear-thickening flow behavior. In the shear-thickening regime, the solutions show vorticity and gradient shear bands simultaneously, in which vorticity shear bands dominate the visual effect, while gradient shear bands always coexist and predominate the rheological response. It is shown that gradient shear bands change their phases (turbid, clear) with the same frequency as the shear rate oscillates, whereas vorticity shear bands change their phases with half the frequency of the shear rate. Furthermore, we show that with increasing molecular mass of the counterions the number of gradient shear bands increases, while the number of vorticity shear bands remains constant. The variation of temperature, shear stress, concentration, and counterions results in a predictable change in the rheological behavior and therefore allows adjustment of the number of vorticity shear bands in the shear band regime.
Creep and recovery of magnetorheological fluids: Experiments and simulations
Authors: Wang Zuowei , Shahrivar Keshvad , de Vicente Juan
Published: September 2014

A direct comparative study on the creep-recovery behavior of conventional magnetorheological (MR) fluids is carried out using magnetorheometry and particle-level simulations. Two particle concentrations are investigated (ϕ=0.05 and 0.30) at two different magnetic field strengths (53 and 173 kA·m−1) in order to match the yield stresses developed in both systems for easier comparison. Simulations are mostly started with random initial structures with some additional tests of using preassembled single chains in the low concentration case. Experimental and simulation data are in good qualitative agreement. The results demonstrate three regions in the creep curves: (i) In the initial viscoelastic region, the chainlike (at ϕ=0.05) or percolated three-dimensional network (at ϕ=0.30) structures fill up the gap and the average cluster size remains constant; (ii) Above a critical strain of 0.1 (10%), in the retardation region, these structures begin to break and rearrange under shear. At large enough imposed stress values, they transform into thin sheetlike or thick lamellar structures, depending on the particle concentration; (iii) Finally in the case of larger strain values either the viscosity diverges (at low stress values) or reaches a constant low value (at high stress values), showing a clear bifurcation behavior. For stresses below the bifurcation point, the MR fluid is capable to recover the strain by a certain fraction. However, no recovery is observed for large stress values.
Improvement of the Classification System for Wheelchair Rugby: Athlete Priorities
Authors: Altmann Viola C. , Van Limbeek Jacques , Hart Anne L. , Vanlandewijck Yves C.
Published: September 2014

A representative sample (N = 302) of the wheelchair rugby population responded to a survey about the classification system based on prioritized items by International Wheelchair Rugby Federation members. Respondents stated, "The classification system is accurate but needs adjustments" (56%), "Any athlete with tetraequivalent impairment should be allowed to compete" (72%), "Athletes with cerebral palsy and other coordination impairments should be classified with a system different than the current one" (75%), and "The maximal value for trunk should be increased from 1.0 to 1.5" (67%). A minority stated, "Wheelchair rugby should only be open to spinal cord injury and other neurological conditions" (36%) and "There should be a 4.0 class" (33%). Results strongly indicated that athletes and stakeholders want adjustments to the classification system in two areas: a focus on evaluation of athletes with impairments other than loss of muscle power caused by spinal cord injury and changes in classification of trunk impairment.
Doing Things My Way: Teaching Physical Education With a Disability
Authors: Grenier Michelle A. , Horrell Andrew , Genovese Bryan
Published: September 2014

Having a disability and being a teacher can be a critical site for examining practices associated with ability, competence, and pedagogy. While there is a growing literature base that examines the experiences of students with disabilities in physical education, there is virtually no research that examines the experiences of physical education teachers with disabilities. Using the capability approach, this article explores the experiences of a physical education teaching intern with a physical disability, significant school members, and the students he interacted with through interviews and documents. The results yielded 3 primary themes. The first, "the fluid nature of the disability discourse," demonstrated the complexity of disability and explored the contrast between static tendencies that stereotype disability and the disability experience. The second theme, "doing things my way," reflected the intern’s need to distinguish himself as a teacher by defining contexts for experiencing competence. The third and final theme, "agent of change," explored how the intern’s experiences as a teacher with a disability informed his educational narrative.
Youth Sport Experiences of Individuals With Attention Deficit/Hyperactivity Disorder
Authors: Lee Homan , Dunn Janice Causgrove , Holt Nicholas L.
Published: September 2014

The purpose of this study was to explore youth sport experiences of individuals with attention deficit/hyperactivity disorder (ADHD). Participants were 6 males (mean age = 22.7 yr) with ADHD who had played 3 or more seasons in team sports during adolescence. Following interpretive phenomenological analysis methodology, each participant completed 2 semistructured interviews. Findings showed that symptoms of ADHD hampered participants’ experiences and led to negative interpersonal and performance-related consequences. On the other hand, participants reported social and stress/energy-release benefits arising from their experiences in sport. Their experiences were therefore complex, and some findings relating to social interactions appeared contradictory (e.g., negative interpersonal experiences vs. social benefits). Supportive coaches, understanding teammates, and personal coping strategies were key factors that enabled participants to realize benefits and, to some degree, mitigate negative consequences associated with their participation in sport.
RNA and dynamic nuclear organization
Authors: Rinn John , Guttman Mitchell
Published: September 2014

Long noncoding RNAs may function as organizing factors that shape the cell nucleus
Development of the annelid axochord: Insights into notochord evolution
Authors: Lauri Antonella , Brunet Thibaut , Handberg-Thorsager Mette , Fischer Antje H.L. , Simakov Oleg , Steinmetz Patrick R. H. , Tomer Raju , Keller Philipp J. , Arendt Detlev
Published: September 2014

Origin of the spine lies in a worm

The notochord, the developmental backbone precursor, defines chordates—the group of animals to which humans belong. The origin of the notochord remains mysterious. Lauri
et al.
report the identification of a longitudinal muscle in an annelid worm that displays striking similarities to the notochord regarding position, developmental origin, and expression profile. Similar muscles, termed axochords, are found in various invertebrate phyla. These data suggest that the last common ancestor of bilaterians already possessed contractile midline tissue that, via stiffening, developed into a cartilaginous rod in the chordate line.

Science
, this issue p.
1365
Strengthening the evidence base for health programming in humanitarian crises
Authors: Ager A. , Burnham G. , Checchi F. , Gayer M. , Grais R. F. , Henkens M. , Massaquoi M. B. F. , Nandy R. , Navarro-Colorado C. , Spiegel P.
Published: September 2014

Given the growing scale and complexity of responses to humanitarian crises, it is important to develop a stronger evidence base for health interventions in such contexts. Humanitarian crises present unique challenges to rigorous and effective research, but there are substantial opportunities for scientific advance. Studies need to focus where the translation of evidence from noncrisis scenarios is not viable and on ethical ways of determining what happens in the absence of an intervention. Robust methodologies suited to crisis settings have to be developed and used to assess interventions with potential for delivery at scale. Strengthening research capacity in the low- to middle-income countries that are vulnerable to crises is also crucial.
Emerging, evolving, and established infectious diseases and interventions
Authors: Halloran M. Elizabeth , Longini Ira M.
Published: September 2014

Planning, implementing, and evaluating interventions against infectious diseases depend on the nature of the infectious disease; the availability of intervention measures; and logistical, economic, and political constraints. Infectious diseases and vaccine- or drug-based interventions can be loosely categorized by the degree to which the infectious disease and the intervention are well established. Pertussis, polio, and measles are three examples of long-known infectious diseases for which global vaccination has dramatically reduced the public health burden. Pertussis vaccination was introduced in the 1940s, polio vaccination in the 1950s, and measles vaccination in the 1960s, nearly eliminating these diseases in many places.
Loss of avian phylogenetic diversity in neotropical agricultural systems
Authors: Frishkoff Luke O. , Karp Daniel S. , M’Gonigle Leithen K. , Mendenhall Chase D. , Zook Jim , Kremen Claire , Hadly Elizabeth A. , Daily Gretchen C.
Published: September 2014

Costa Rican birds of a feather lost together

Evolutionary history is lost when land is converted for farming, and recently evolved species may cope better with changing land use. Frishkoff
et al.
compared bird diversity over 12 years in three different kinds of landscape in tropical Central America. They mapped their data onto the bird evolutionary tree and found that more evolutionary branches were lost in intensive agricultural landscapes than in mixed landscapes. In turn, mixed landscapes lost more evolutionary branches than forest reserves. This is not just because of species loss; in fact, mixed agricultural landscapes contained similar numbers of species to those in forest reserves. Evolutionary history is lost because the more evolutionarily distinct species—those with fewer extant relatives and a longer evolutionary history—are more likely to become extinct in agricultural land.

Science
, this issue p.
1343
Boundary condition of grounding lines prior to collapse, Larsen-B Ice Shelf, Antarctica
Authors: Rebesco M. , Domack E. , Zgur F. , Lavoie C. , Leventer A. , Brachfeld S. , Willmott V. , Halverson G. , Truffer M. , Scambos T. , Smith J. , Pettit E.
Published: September 2014

Top-down rather than bottom-up change

The Larsen-B Ice Shelf in Antarctica collapsed in 2002 because of a regional increase in surface temperature. This finding, reported by Rebesco
et al.
, will surprise many who supposed that the shelf's disintegration probably occurred because of thinning of the ice shelf and the resulting loss of support by the sea floor beneath it. The authors mapped the sea floor beneath the ice shelf before it fell apart, which revealed that the modern ice sheet grounding line was established around 12,000 years ago and has since remained unchanged. If the ice shelf did not collapse because of thinning from below, then it must have been caused by warming from above.

Science
, this issue p.
1354
Getting essential health products to their end users: Subsidize, but how much?
Authors: Dupas Pascaline
Published: September 2014

Although coverage rates and health outcomes are improving, many poor people around the world still do not benefit from essential health products. An estimated two-thirds of child deaths could be prevented with increased coverage of products such as vaccines, point-of-use water treatment, iron fortification, and insecticide-treated bednets. What limits the flow of products from the producer’s laboratory bench to the end users, and what can be done about it? Recent empirical research suggests a crucial role for heavy subsidies.
The state of global health in 2014
Authors: Sepúlveda Jaime , Murray Christopher
Published: September 2014

The global health landscape looks more promising than ever, although progress has been uneven. Here, we describe the current global burden of disease throughout the life cycle, highlighting regional differences in the unfinished agenda of communicable diseases and reproductive, maternal, and child health and the additive burden of emerging noncommunicable diseases and injuries. Understanding this changing landscape is an essential starting point for effective allocation of both domestic and international resources for health.
Decoupled catalytic hydrogen evolution from a molecular metal oxide redox mediator in water splitting
Authors: Rausch Benjamin , Symes Mark D. , Chisholm Greig , Cronin Leroy
Published: September 2014

Scheduling hydrogen release from water

Photosynthesis splits water to provide protons and electrons for plant growth; oxygen is a by-product. When chemists split water, they're also more interested in making fuel, and the simplest product is hydrogen (a combination of protons and electrons). One challenge is keeping the reactive hydrogen and oxygen product streams separate. Rausch
et al.
present a scheme that captures the protons and electrons in a molecular cluster of silico-tungstic acid. Later, they expose the cluster to platinum, coaxing the acid into releasing hydrogen. Eliminating the mixing risk increases the potential for household use.

Science
, this issue p.
1326
Models of education in medicine, public health, and engineering
Authors: Garcia Patricia , Armstrong Robert , Zaman Muhammad H.
Published: September 2014

Discussion on global health in both the academic and the public domain has focused largely on research, capacity building, and service delivery. Although these efforts along with financial commitments from public and private partners have contributed to a broader appreciation and understanding of global health challenges, the reflection of global health in academic training has largely been lacking. However, integrative models are beginning to appear.
Prioritizing integrated mHealth strategies for universal health coverage
Authors: Mehl Garrett , Labrique Alain
Published: September 2014

As countries strive toward universal health coverage, mobile wireless technologies—mHealth tools—in support of enumeration, registration, unique identification, and maintenance of health records will facilitate improved health system performance. Electronic forms and registry systems will enable routine monitoring of the coverage of essential interventions for individuals within relevant target populations. A cascading model is presented for prioritizing and operationalizing the role of integrated mHealth strategies.
Monitoring parasite diversity for malaria elimination in sub-Saharan Africa
Authors: Ghansah Anita , Amenga-Etego Lucas , Amambua-Ngwa Alfred , Andagalu Ben , Apinjoh Tobias , Bouyou-Akotet Marielle , Cornelius Victoria , Golassa Lemu , Andrianaranjaka Voahangy Hanitriniaina , Ishengoma Deus , Johnson Kimberly , Kamau Edwin , Maïga-Ascofaré Oumou , Mumba Dieudonne , Tindana Paulina , Tshefu-Kitoto Antoinette , Randrianarivelojosia Milijaona , William Yavo , Kwiatkowski Dominic P. , Djimde Abdoulaye A.
Published: September 2014

The African continent continues to bear the greatest burden of malaria and the greatest diversity of parasites, mosquito vectors, and human victims. The evolutionary plasticity of malaria parasites and their vectors is a major obstacle to eliminating the disease. Of current concern is the recently reported emergence of resistance to the front-line drug, artemisinin, in South-East Asia in
Plasmodium falciparum
, which calls for preemptive surveillance of the African parasite population for genetic markers of emerging drug resistance. Here we describe the Plasmodium Diversity Network Africa (PDNA), which has been established across 11 countries in sub-Saharan Africa to ensure that African scientists are enabled to work together and to play a key role in the global effort for tracking and responding to this public health threat.
Morality beyond the lab
Authors: Graham Jesse
Published: September 2014

Much of moral life involves attending to our own good deeds and to the bad deeds of others

[Also see Report by

Hofmann
et al.

]
Innate lymphoid cells sweeten the pot
Authors: Hooper Lora V.
Published: September 2014

Immune cells prompt gut epithelial cells to produce carbohydrate nutrients for resident bacteria

[Also see Research Article by

Goto
et al.

]
Halving premature death
Authors: Peto Richard , Lopez Alan D. , Norheim Ole F.
Published: September 2014

Death in old age is inevitable, but death before old age is not. Except where HIV or political disturbances predominated, mortality rates have been decreasing for decades, helped by sanitation, health care, and social changes. Even in low-income countries, at current death rates, three-quarters of newborn infants would survive to age 50, and half would survive to age 70. If disease control keeps progressing and economic development proceeds, then within the next few decades—except where disasters or new epidemics supervene—under-50 mortality should fall to less than half of today's 15% global risk, and under-70 mortality should be less than one in six.
China blamed for U.S. ozone
Authors: Hand Eric
Published: September 2014

Western states caught between rising background levels and more stringent federal limits.
It's a wash: Hands-on hygiene in Peru
Authors: Kupferschmidt Kai
Published: September 2014

A simple fix proves elusive.
A new vaccine vanquishes meningitis A in Africa
Authors: Kupferschmidt Kai
Published: September 2014

The first vaccine developed specifically for Africa is an unqualified success.
Multicultural relationships: Working across industries
Authors: Tachibana Chris
Published: September 2014

Academic researchers are increasingly venturing out of the laboratory and into unfamiliar professional territory. The draw might be a multidisciplinary project, industry collaboration, or consulting. The new field might be government, law, or
even the military. To ease interactions with colleagues in other fields with different work environments, seven researchers
share what they've learned about productive, professional cross-disciplinary relationships.
Phenotypic and Molecular Characteristics of Carbapenem-Resistant Enterobacteriaceae in a Health Care System in Los Angeles, California, from 2011 to 2013
Authors: Pollett S. , Miller S. , Hindler J. , Uslan D. , Carvalho M. , Humphries R. M.
Published: September 2014

Carbapenem-resistant
Enterobacteriaceae
(CRE) are a concern for health care in the United States but remain relatively uncommon in California. We describe the phenotype, clonality, and carbapenemase-encoding genes present in CRE isolated from patients at a Californian tertiary health care system. CRE for this study were identified by evaluating the antibiograms of
Enterobacteriaceae
isolated in the UCLA Health System from 2011 to 2013 for isolates that were not susceptible to meropenem and/or imipenem. The identification of these isolates was subsequently confirmed by matrix-associated laser desorption ionization–time of flight, and broth microdilution tests were repeated to confirm the CRE phenotype. Real-time PCR for
bla
KPC
,
bla
SME
,
bla
IMP
,
bla
NDM-1
,
bla
VIM
, and
bla
OXA-48
was performed. Clonality was assessed by repetitive sequence-based PCR (repPCR) and multilocus sequence typing (MLST). Of 15,839 nonduplicate clinical
Enterobacteriaceae
isolates, 115 (0.73%) met the study definition for CRE. This number increased from 0.5% (44/8165) in the first half of the study to 0.9% (71/7674) in the second (
P
= 0.004). The most common CRE species were
Klebsiella pneumoniae
,
Enterobacter aerogenes
, and
Escherichia coli
. A carbapenemase-encoding gene was found in 81.7% (94/115) of CRE and included
bla
KPC
(78.3%),
bla
NDM-1
(0.9%), and
bla
SME
(2.6%). The majority of
bla
KPC
genes were in
K. pneumoniae
isolates, which fell into 14 clonal groups on typing.
bla
KPC
was identified in more than one species of CRE cultured from the same patient in four cases. Three
bla
SME
-carrying
Serratia marcescens
isolates and one
bla
NDM-1
carrying
Providencia rettgeri
isolate were detected. CRE are increasing in California, and carbapenemases, particularly KPC, are a common mechanism for carbapenem resistance in this region.
Prolonged Second Diagnostic Window for Human Immunodeficiency Virus Type 1 in a Fourth-Generation Immunoassay: Are Alternative Testing Strategies Required?
Authors: George C. R. Robert , Robertson Peter W. , Lusk M. Josephine , Whybin Ross , Rawlinson William
Published: September 2014

Diagnosis of acute HIV is done by patient history and examination and testing of RNA, proviral DNA, and serology using fourth-generation antigen/antibody detection assays. We describe an HIV-1 primary infection with a second diagnostic window of 18 to 34 days on a fourth-generation immunoassay, which would have been missed using some current algorithms. Caution must be exercised when fourth-generation HIV-1 immunoassays are interpreted in isolation, and additional testing should be considered depending on patient risk assessment.
Multilocus Sequence Typing of Mycobacterium xenopi
Authors: Alexander David C. , Marras Theodore K. , Ma Jennifer H. , Mirza Samia , Liu Daniel , Kus Julianne V. , Soualhine Hafid , Escuyer Vincent , Warshauer David , Brode Sarah K. , Farrell David J. , Jamieson Frances B.
Published: September 2014

Mycobacterium xenopi
is an opportunistic mycobacterial pathogen of increasing clinical importance. Surveillance of
M. xenopi
is hampered by the absence of tools for genotyping and molecular epidemiology. In this study, we describe the development and evaluation of an effective multilocus sequence typing strategy for
M. xenopi
.
Evaluation of the Alere i Influenza A&B Nucleic Acid Amplification Test by Use of Respiratory Specimens Collected in Viral Transport Medium
Authors: Bell J. Jeremiah , Selvarangan Rangaraj
Published: September 2014

The Alere i Influenza A&B assay is a newly developed rapid molecular assay which has the potential to generate results within 15 min from sample collection. In this study, we evaluated the Alere i Influenza A&B assay by using salvaged frozen respiratory specimens that were collected in viral transport medium from children ages 10 months to 19 years. Alere i Influenza A&B assay test results were compared with viral culture and ProFlu
+
real-time reverse transcription-PCR (RT-PCR) assay results. We found that the overall sensitivity and specificity of the Alere i Influenza A&B assay were 93.3% and 94.5% for the detection of influenza A virus and 100% and 100% for the detection of influenza B virus, respectively, compared to viral culture. In comparison to ProFlu
+
real-time RT-PCR, overall sensitivity and specificity of the Alere i Influenza A&B assay for the detection of influenza A virus were 88.8% and 98.3% and 100% and 100% for detecting influenza B virus. Overall, the Alere i Influenza A&B assay performed well compared to either virus cell culture or RT-PCR.
PCR-Based Detection of Toxoplasma gondii DNA in Blood and Ocular Samples for Diagnosis of Ocular Toxoplasmosis
Authors: Bourdin C. , Busse A. , Kouamou E. , Touafek F. , Bodaghi B. , Le Hoang P. , Mazier D. , Paris L. , Fekkar A.
Published: September 2014

PCR detection of
Toxoplasma gondii
in blood has been suggested as a possibly efficient method for the diagnosis of ocular toxoplasmosis (OT) and furthermore for genotyping the strain involved in the disease. To assess this hypothesis, we performed PCR with 121 peripheral blood samples from 104 patients showing clinical and/or biological evidence of ocular toxoplasmosis and from 284 (258 patients) controls. We tested 2 different extraction protocols, using either 200 μl (small volume) or 2 ml (large volume) of whole blood. Sensitivity was poor, i.e., 4.1% and 25% for the small- and large-volume extractions, respectively. In comparison, PCR with ocular samples yielded 35.9% sensitivity, while immunoblotting and calculation of the Goldmann-Witmer coefficient yielded 47.6% and 72.3% sensitivities, respectively. Performing these three methods together provided 89.4% sensitivity. Whatever the origin of the sample (ocular or blood), PCR provided higher sensitivity for immunocompromised patients than for their immunocompetent counterparts. Consequently, PCR detection of
Toxoplasma gondii
in blood samples cannot currently be considered a sufficient tool for the diagnosis of OT, and ocular sampling remains necessary for the biological diagnosis of OT.
Evaluation of Five Real-Time PCR Assays for Detection of Mycoplasma pneumoniae
Authors: Dumke Roger , Jacobs Enno
Published: September 2014

Four commercial real-time PCR assays to detect
Mycoplasma pneumoniae
were tested, and the results were compared with the results for an in-house approach. Despite differences of crossing threshold values of up to 4, assays were able to detect at least 20 CFU/5 μl (52 fg DNA/5 μl) of sample with the Diagenode kit showing the best clinical sensitivity.
Interaction of Adenovirus Type 5 E4orf4 with the Nuclear Pore Subunit Nup205 Is Required for Proper Viral Gene Expression
Authors: Lu YiQing , Kucharski Thomas J. , Gamache Isabelle , Blanchette Paola , Branton Philip E. , Teodoro Jose G.
Published: September 2014

Adenovirus type 5 E4orf4 is a multifunctional protein that regulates viral gene expression. The activities of E4orf4 are mainly mediated through binding to protein phosphatase 2A (PP2A). E4orf4 recruits target phosphoproteins into complexes with PP2A, resulting in dephosphorylation of host factors, such as SR splicing factors. In the current study, we utilized immunoprecipitation followed by mass spectrometry to identify novel E4orf4-interacting proteins. In this manner we identified Nup205, a component of the nuclear pore complex (NPC) as an E4orf4 interacting partner. The arginine-rich motif (ARM) of E4orf4 was required for interaction with Nup205 and for nuclear localization of E4orf4. ARMs are commonly found on viral nuclear proteins, and we observed that Nup205 interacts with three different nuclear viral proteins containing ARMs. E4orf4 formed a trimolecular complex containing both Nup205 and PP2A. Furthermore, Nup205 complexed with E4orf4 was hypophosphorylated, suggesting that the protein is specifically targeted for dephosphorylation. An adenovirus mutant that does not express E4orf4 (Orf4
−
) displayed elevated early and reduced late gene expression relative to that of the wild type. We observed that knockdown of Nup205 resulted in the same phenotype as that of the Orf4
−
virus, suggesting that the proteins function as a complex to regulate viral gene expression. Furthermore, knockdown of Nup205 resulted in a more than a 4-fold reduction in the replication of wild-type adenovirus. Our data show for first time that Ad5 E4orf4 interacts with and modifies the NPC and that Nup205-E4orf4 binding is required for normal regulation of viral gene expression and viral replication.

IMPORTANCE
Nuclear pore complexes (NPCs) are highly regulated conduits in the nuclear membrane that control transport of macromolecules between the nucleus and cytoplasm. Viruses that replicate in the nucleus must negotiate the NPC during nuclear entry, and viral DNA, mRNA, and proteins must then be exported from the nucleus. Several types of viruses restructure the NPC to facilitate replication, and the current study shows that adenovirus type 5 (Ad5) utilizes a novel mechanism to modify NPC function. We demonstrate that a subunit of the NPC, Nup205, is a phosphoprotein that is actively dephosphorylated by the Ad5-encoded protein E4orf4. Moreover, Nup205 is required by Ad5 to regulate viral gene expression and efficient viral replication. Nup205 is a nonstructural subunit that is responsible for the gating functions of the NPC, and this study suggests for the first time that the NPC is regulated by phosphorylation both during normal physiology and viral infection.
Mutations to PB2 and NP Proteins of an Avian Influenza Virus Combine To Confer Efficient Growth in Primary Human Respiratory Cells
Authors: Danzy Shamika , Studdard Lydia R. , Manicassamy Balaji , Solorzano Alicia , Marshall Nicolle , García-Sastre Adolfo , Steel John , Lowen Anice C.
Published: September 2014

Influenza pandemics occur when influenza A viruses (IAV) adapted to other host species enter humans and spread through the population. Pandemics are relatively rare due to host restriction of IAV: strains adapted to nonhuman species do not readily infect, replicate in, or transmit among humans. IAV can overcome host restriction through reassortment or adaptive evolution, and these are mechanisms by which pandemic strains arise in nature. To identify mutations that facilitate growth of avian IAV in humans, we have adapted influenza A/duck/Alberta/35/1976 (H1N1) (dk/AB/76) virus to a high-growth phenotype in differentiated human tracheo-bronchial epithelial (HTBE) cells. Following 10 serial passages of three independent lineages, the bulk populations showed similar growth in HTBE cells to that of a human seasonal virus. The coding changes present in six clonal isolates were determined. The majority of changes were located in the polymerase complex and nucleoprotein (NP), and all isolates carried mutations in the PB2 627 domain and regions of NP thought to interact with PB2. Using reverse genetics, the impact on growth and polymerase activity of individual and paired mutations in PB2 and NP was evaluated. The results indicate that coupling of the mammalian-adaptive mutation PB2 E627K or Q591K to selected mutations in NP further augments the growth of the corresponding viruses. In addition, minimal combinations of three (PB2 Q236H, E627K, and NP N309K) or two (PB2 Q591K and NP S50G) mutations were sufficient to recapitulate the efficient growth in HTBE cells of dk/AB/76 viruses isolated after 10 passages in this substrate.

IMPORTANCE
Influenza A viruses adapted to birds do not typically grow well in humans. However, as has been seen recently with H5N1 and H7N9 subtype viruses, productive and virulent infection of humans with avian influenza viruses can occur. The ability of avian influenza viruses to adapt to new host species is a consequence of their high mutation rate that supports their zoonotic potential. Understanding of the adaptation of avian viruses to mammals strengthens public health efforts aimed at controlling influenza. In particular, it is critical to know how readily and through mutation to which functional components avian influenza viruses gain the ability to grow efficiently in humans. Our data show that as few as three mutations, in the PB2 and NP proteins, support robust growth of a low-pathogenic, H1N1 duck isolate in primary human respiratory cells.
Viruses and RNA Interference: Issues and Controversies
Authors: Cullen Bryan R.
Published: September 2014

The question of whether any mammalian cells are able to mount an effective RNA interference-mediated antiviral innate immune response has remained highly controversial. In this Gem, I review recent data addressing this important issue and propose a testable hypothesis that can explain many of the apparently contradictory results published in this area of research.
A Bivalent Vaccine Based on a Replication-Incompetent Influenza Virus Protects against Streptococcus pneumoniae and Influenza Virus Infection
Authors: Katsura Hiroaki , Piao Zhenyu , Iwatsuki-Horimoto Kiyoko , Akeda Yukihiro , Watanabe Shinji , Horimoto Taisuke , Oishi Kazunori , Kawaoka Yoshihiro
Published: September 2014

Streptococcus pneumoniae
is a major causative pathogen in community-acquired pneumonia; together with influenza virus, it represents an important public health burden. Although vaccination is the most effective prophylaxis against these infectious agents, no single vaccine simultaneously provides protective immunity against both
S. pneumoniae
and influenza virus. Previously, we demonstrated that several replication-incompetent influenza viruses efficiently elicit IgG in serum and IgA in the upper and lower respiratory tracts. Here, we generated a replication-incompetent hemagglutinin knockout (HA-KO) influenza virus possessing the sequence for the antigenic region of pneumococcal surface protein A (PspA). Although this virus (HA-KO/PspA virus) could replicate only in an HA-expressing cell line, it infected wild-type cells and expressed both viral proteins and PspA. PspA- and influenza virus-specific antibodies were detected in nasal wash and bronchoalveolar lavage fluids and in sera from mice intranasally inoculated with HA-KO/PspA virus, and mice inoculated with HA-KO/PspA virus were completely protected from lethal challenge with either
S. pneumoniae
or influenza virus. Further, bacterial colonization of the nasopharynx was prevented in mice immunized with HA-KO/PspA virus. These results indicate that HA-KO/PspA virus is a promising bivalent vaccine candidate that simultaneously confers protective immunity against both
S. pneumoniae
and influenza virus. We believe that this strategy offers a platform for the development of bivalent vaccines, based on replication-incompetent influenza virus, against pathogens that cause respiratory infectious diseases.

IMPORTANCE
Streptococcus pneumoniae
and influenza viruses cause contagious diseases, but no single vaccine can simultaneously provide protective immunity against both pathogens. Here, we used reverse genetics to generate a replication-incompetent influenza virus carrying the sequence for the antigenic region of pneumococcal surface protein A and demonstrated that mice immunized with this virus were completely protected from lethal doses of infection with either influenza virus or
Streptococcus pneumoniae
. We believe that this strategy, which is based on a replication-incompetent influenza virus possessing the antigenic region of other respiratory pathogens, offers a platform for the development of bivalent vaccines.