bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of Actinobacillus pleuropneumoniae infection on tulathromycin pharmacokinetics and lung tissue disposition in pigs
Authors: Gajda A. , Bladek T. , Jablonski A. , Posyniak A.
Published: August 2015

A tulathromycin concentration and pharmacokinetic parameters in plasma and lung tissue from healthy pigs and Actinobacillus pleuropneumoniae (App)‐infected pigs were compared. Tulathromycin was administered intramuscularly (i.m.) to all pigs at a single dose of 2.5 mg/kg. Blood and lung tissue samples were collected during 33 days postdrug application. Tulathromycin concentration in plasma and lung was determined by high‐performance liquid chromatography with tandem mass spectrometry (LC‐MS/MS) method. The mean maximum plasma concentration (Cmax) in healthy pigs was 586 ± 71 ng/mL, reached by 0.5 h, while the mean value for Cmax of tulathromycin in infected pigs was 386 ± 97 ng/mL after 0.5 h. The mean maximum tulathromycin concentration in lung of healthy group was calculated as 3412 ± 748 ng/g, detected at 12 h, while in pigs with App, the highest concentration in lung was 3337 ± 937 ng/g, determined at 48 h postdosing. The higher plasma and lung concentrations in pigs with no pulmonary inflammation were observed at the first time points sampling after tulathromycin administration, but slower elimination with elimination half‐life t1/2el = 126 h in plasma and t1/2el = 165 h in lung, as well as longer drug persistent in infected pigs, was found.
Inappropriate Processes and Unbalanced Outcomes: Plant Variety Protection in Africa Goes Beyond UPOV 1991 Requirements
Authors: Haugen Hans Morten
Published: August 2015

The African Regional Intellectual Property Organization (ARIPO) has traditionally been skeptical toward the African Intellectual Property Organization's (OAPI) approval in 1999 of a plant variety protection that was compatible with UPOV 1991, a convention adopted by the International Union for the Protection of New Varieties of Plants. Recently, however, ARIPO has been rushing through a plant variety protection (PVP) protocol, that in April 2014 was found by the UPOV Council to be in conformity with UPOV 1991. The article draws upon theories identifying under which conditions secretariats of international organizations (IOs) are able to operate without too stringent supervision and control by states. These theories goes beyond standars principal‐agent theories, identifying IOs that regulate issues requiring high levels of expertise. Based on this general model, the article investigates both the process and the outcome of the ARIPO Arusha PVP Protocol. It finds that the interests of breeders prevail, while farmers’ organizations and organizations promoting the public interest are to a large extent sidelined from the negotiations. The article then analyzes the content of the recently adopted Tanzanian Plant Breeders Rights Act, noting that several provisions go beyond the UPOV 1991 requirements. The article calls for the more flexible approach of the TRIPS Agreement.
MinC/MinD copolymers are not required for Min function
Authors: Park Kyung‐Tae , Du Shishen , Lutkenhaus Joe
Published: August 2015

In Escherichia coli, precise placement of the cytokinetic Z ring at midcell requires the concerted action of the three Min proteins. MinD activates MinC, an inhibitor of FtsZ, at least in part, by recruiting it to the membrane and targeting it to the Z ring, while MinE stimulates the MinD ATPase inducing an oscillation that directs MinC/MinD activity away from midcell. Recently, MinC and MinD were shown to form copolymers of alternating dimers of MinC and MinD, and it was suggested that these copolymers are the active form of MinC/MinD. Here, we use MinD mutants defective in binding MinC to generate heterodimers with wild‐type MinD that are unable to form MinC/MinD copolymers. Similarly, MinC mutants defective in binding to MinD were used to generate heterodimers with wild‐type MinC that are unable to form copolymers. Such heterodimers are active and in the case of MinC were shown to mediate spatial regulation of the Z ring demonstrating that MinC/MinD copolymer formation is not required. Our results are consistent with a model in which a membrane anchored MinC/MinD complex is targeted to the Z ring through the conserved carboxy tail of FtsZ leading to breakage of FtsZ filaments.
Full engagement of liganded maltose‐binding protein stabilizes a semi‐open ATP‐binding cassette dimer in the maltose transporter
Authors: Alvarez Frances Joan D. , Orelle Cédric , Huang Yan , Bajaj Ruchika , Everly R. Michael , Klug Candice S. , Davidson Amy L.
Published: August 2015

MalFGK2 is an ATP‐binding cassette (ABC) transporter that mediates the uptake of maltose/maltodextrins into Escherichia coli. A periplasmic maltose‐binding protein (MBP) delivers maltose to the transmembrane subunits (MalFG) and stimulates the ATPase activity of the cytoplasmic nucleotide‐binding subunits (MalK dimer). This MBP‐stimulated ATPase activity is independent of maltose for purified transporter in detergent micelles. However, when the transporter is reconstituted in membrane bilayers, only the liganded form of MBP efficiently stimulates its activity. To investigate the mechanism of maltose stimulation, electron paramagnetic resonance spectroscopy was used to study the interactions between the transporter and MBP in nanodiscs and in detergent. We found that full engagement of both lobes of maltose‐bound MBP unto MalFGK2 is facilitated by nucleotides and stabilizes a semi‐open MalK dimer. Maltose‐bound MBP promotes the transition to the semi‐open state of MalK when the transporter is in the membrane, whereas such regulation does not require maltose in detergent. We suggest that stabilization of the semi‐open MalK2 conformation by maltose‐bound MBP is key to the coupling of maltose transport to ATP hydrolysis in vivo, because it facilitates the progression of the MalK dimer from the open to the semi‐open conformation, from which it can proceed to hydrolyze ATP.
The mycobacterial iron‐dependent regulator IdeR induces ferritin (bfrB) by alleviating Lsr2 repression
Authors: Kurthkoti Krishna , Tare Priyanka , Paitchowdhury Rakhi , Gowthami Vykuntham Naga , Garcia Maria J. , Colangeli Roberto , Chatterji Dipankar , Nagaraja Valakunja , Rodriguez G. Marcela
Published: August 2015

Emerging evidence indicates that precise regulation of iron (Fe) metabolism and maintenance of Fe homeostasis in Mycobacterium tuberculosis (Mtb) are essential for its survival and proliferation in the host. IdeR is a central transcriptional regulator of Mtb genes involved in Fe metabolism. While it is well understood how IdeR functions as a repressor, how it induces transcription of a subset of its targets is still unclear. We investigated the molecular mechanism of IdeR‐mediated positive regulation of bfrB, the gene encoding the major Fe‐storage protein of Mtb. We found that bfrB induction by Fe required direct interaction of IdeR with a DNA sequence containing four tandem IdeR‐binding boxes located upstream of the bfrB promoter. Results of in vivo and in vitro transcription assays identified a direct repressor of bfrB, the histone‐like protein Lsr2. IdeR counteracted Lsr2‐mediated repression in vitro, suggesting that IdeR induces bfrB transcription by antagonizing the repressor activity of Lsr2. Together, these results elucidate the main mechanism of bfrB positive regulation by IdeR and identify Lsr2 as a new factor contributing to Fe homeostasis in mycobacteria.
The Political Structure of Policy Diffusion
Authors: Fay Daniel L. , Wenger Jeffrey B.
Published: August 2015

Unlike the U.S. Constitution, many state constitutions include provisions for regulating and legislating specific policy issues. Embedding policy proscriptions in state constitutions may impact the rate and likelihood of policy diffusion. To examine how the amendment process influences diffusion resulting from geographic competition, we estimate a well‐known policy diffusion model, using state‐sponsored lotteries as a case study. Our mixed model of survival analysis separately estimates amendments and lottery adoptions allowing for different covariates and baseline hazards in each model. We find that there are different diffusion effects for constitutional amendments and policy adoptions, that the two‐step process requires a more professionalized legislature, and that amending the state constitution influences the timing of the adoption process. Once we take into consideration the two‐step process of lottery diffusion, we find a conditional diffusion effect that is over twice as large as previous estimates, and an overall diffusion that is larger than estimates from event‐history estimation, suggesting that the constitutional hurdle is an important determinant of policy adoption. These effects occur over the entire policy adoption phase (1961–2009), over multiple specifications of the baseline hazard, for alternate measures of diffusion, and for alternate model specifications, thereby suggesting that the constitutional hurdle is an important element of state policy, and it should be empirically considered in future models of policy diffusion.
Some Conceptual Aspects of Temporality and the Ability to Possess Rights
Authors: Sreekumar Sandeep
Published: August 2015

Since certain temporal aspects of the relation between duties, rights, and the interests that rights protect have not been fully theorized, a puzzle arises when we come to consider whether and how entities such as members of future generations, fetuses, deceased persons, and unconscious persons are able to possess rights. This paper evolves a unified structure for attributing the ability to possess rights to such entities. It demonstrates that while, under any cogent theory of rights‐attributions, rights and duties must be strictly contemporaneous, the interests that rights protect need not temporally coincide with those rights.
Cost‐effective ecological restoration
Authors: Kimball Sarah , Lulow Megan , Sorenson Quinn , Balazs Kathleen , Fang Yi‐Chin , Davis Steven J. , O'Connell Michael , Huxman Travis E.
Published: August 2015

Ecological restoration is a multibillion dollar industry critical for improving degraded habitat. However, most restoration is conducted without clearly defined success measures or analysis of costs. Outcomes are influenced by environmental conditions that vary across space and time, yet such variation is rarely considered in restoration planning. Here, we present a cost‐effectiveness analysis of terrestrial restoration methods to determine how practitioners may restore the highest native plant cover per dollar spent. We recorded costs of 120 distinct methods and described success in terms of native versus non‐native plant germination, growth, cover, and density. We assessed effectiveness using a basic, commonly used metric (% native plant cover) and developed an index of cost‐effectiveness (% native cover per dollar spent on restoration). We then evaluated success of multiple methods, given environmental variation across topography and multiple years, and found that the most successful method for restoring high native plant cover is often different from the method that results in the largest area restored per dollar expended, given fixed mitigation budgets. Based on our results, we developed decision‐making trees to guide practitioners through established phases of restoration—site preparation, seeding and planting, and maintenance. We also highlight where additional research could inform restoration practice, such as improved seasonal weather forecasts optimizing allocation of funds in time or valuation practices that include costs of specific outcomes in the collection of in lieu fees.
Risk Preferences, Probability Weighting, and Strategy Tradeoffs in Wildfire Management
Authors: Hand Michael S. , Wibbenmeyer Matthew J. , Calkin David E. , Thompson Matthew P.
Published: August 2015

Wildfires present a complex applied risk management environment, but relatively little attention has been paid to behavioral and cognitive responses to risk among public agency wildfire managers. This study investigates responses to risk, including probability weighting and risk aversion, in a wildfire management context using a survey‐based experiment administered to federal wildfire managers. Respondents were presented with a multiattribute lottery‐choice experiment where each lottery is defined by three outcome attributes: expenditures for fire suppression, damage to private property, and exposure of firefighters to the risk of aviation‐related fatalities. Respondents choose one of two strategies, each of which includes “good” (low cost/low damage) and “bad” (high cost/high damage) outcomes that occur with varying probabilities. The choice task also incorporates an information framing experiment to test whether information about fatality risk to firefighters alters managers' responses to risk. Results suggest that managers exhibit risk aversion and nonlinear probability weighting, which can result in choices that do not minimize expected expenditures, property damage, or firefighter exposure. Information framing tends to result in choices that reduce the risk of aviation fatalities, but exacerbates nonlinear probability weighting.
Conflict or Caveats? Effects of Media Portrayals of Scientific Uncertainty on Audience Perceptions of New Technologies
Authors: Binder Andrew R. , Hillback Elliott D. , Brossard Dominique
Published: August 2015

Research indicates that uncertainty in science news stories affects public assessment of risk and uncertainty. However, the form in which uncertainty is presented may also affect people's risk and uncertainty assessments. For example, a news story that features an expert discussing both what is known and what is unknown about a topic may convey a different form of scientific uncertainty than a story that features two experts who hold conflicting opinions about the status of scientific knowledge of the topic, even when both stories contain the same information about knowledge and its boundaries. This study focuses on audience uncertainty and risk perceptions regarding the emerging science of nanotechnology by manipulating whether uncertainty in a news story about potential risks is attributed to expert sources in the form of caveats (individual uncertainty) or conflicting viewpoints (collective uncertainty). Results suggest that the type of uncertainty portrayed does not impact audience feelings of uncertainty or risk perceptions directly. Rather, the presentation of the story influences risk perceptions only among those who are highly deferent to scientific authority. Implications for risk communication theory and practice are discussed.
Multi‐Local Living Arrangements: Approaches to Quantification in German Language Official Statistics and Surveys
Authors: Dittrich‐Wesbuer Andrea , Kramer Caroline , Duchêne‐Lacroix Cédric , Rumpolt Peter
Published: August 2015

Quantification of multi‐local forms of living has been an urgent need expressed by science, planning, and politics. In the present paper, this aim is pursued by analysing sources of official statistics in Germany, Austria and Switzerland. The available data sources turn out to differ in the three countries as regards content‐related accuracy and depth as well as spatio‐temporal differentiation. This forms the frame for discussing conceptual and methodological implications for future survey and evaluation practices and for pointing out both the problems and the prospects of quantifying this phenomenon.
Consequences of severe obstetric complications on women's health in Morocco: please, listen to me!
Authors: Assarag Bouchra , Dujardin Bruno , Essolbi Amina , Cherkaoui Imad , De Brouwere Vincent
Published: August 2015

Objective

In Morocco, medical care for women with severe obstetric complications (near‐miss cases) ends at discharge from the hospital. Little information exists regarding what happens after returning home. The aim of the study was to assess the physical and mental health consequences of near‐miss events on Moroccan women 8 months after childbirth.

Methods

A prospective cohort study of 76 near‐miss women was conducted in three hospitals. For every case, we recruited at least two women from the same hospital who had uncomplicated deliveries (n = 169). We used a mixed‐methods approach. For the quantitative part, we analysed sociodemographic characteristics collected via a questionnaire and medical complications extracted from the medical records during a medical consultation at 8 months post‐partum. Forty in‐depth interviews were also conducted with 20 near‐miss cases and 20 women with uncomplicated deliveries.

Results

The near‐miss women were poorer and less educated than those who had uncomplicated deliveries. The proportion of physical consequences (serious illness) was higher among near‐miss cases (22%) than uncomplicated deliveries (6%, P = 0.001). The risk of depression was significantly higher among near‐miss cases with perinatal death (OR = 7.16; [95% CI: 2.85–17.98]) than among those who had an uncomplicated delivery. Interviews revealed that the economic burden of near‐miss care contributed to social problems among the women and their households.

Conclusion

A near‐miss event has consequences that go beyond the first days after delivery. Developing new mechanisms for maternal and newborn health follow‐up is essential and should address the mother's physical and mental health problems and involve husbands and family members.
The Quest for Robust Counterfeit and Piracy Figures: Custom Agencies as Statistical Decision‐makers and Recent Evidence Based on German Imports
Authors: Cuntz Alexander
Published: August 2015

Based on unique custom seizure data, we extrapolate robust figures on the amount of counterfeit and piracy in German imports. We therefore outline a simple model which explores estimation biases in counterfeit statistics provided by utility‐maximising custom agencies. Our empirical strategy sets out to (i) provide evidence on bias and, (ii) guided by theory, identify an unbiased subsample of the data. Upper bound population estimates (counterfeit shares) for 2010–11 suggest that around 17 per cent of all German imports are counterfeit. In addition, we highlight differences in counterfeit trade by commodity and distribution channel, and conclude with policy advice.
PGC‐1α gene transfer improves muscle function in dystrophic muscle following prolonged disease progress
Authors: Hollinger Katrin , Selsby Joshua T.
Published: August 2015

New Findings

What is the central question of this study?

Peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) gene transfer as a treatment for Duchenne muscular dystrophy is efficacious even with advanced disease.

What is the main finding and its importance?

PGC‐1α pathway activation strategies may be most effective when initiated at the earliest possible time.

Duchenne muscular dystrophy is a progressive and fatal muscle wasting disease caused by a dystrophin deficiency. We previously found that gene transfer of peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) increased abundance of utrophin and increased mitochondrial biogenesis using prevention and rescue treatment protocols. Our purpose in this investigation was to determine the extent to which PGC‐1α gene transfer would rescue dystrophic muscle following prolonged disease progression. One‐year‐old mdx mice from our colony were injected in one hindlimb with a virus driving expression of PGC‐1α, while the contralateral limb was injected with empty capsid. Three months after viral gene transfer, PGC‐1α expression was 40‐fold greater than in contralateral limbs. Specific tension was increased by ∼60% (P < 0.05), and force produced during the final contraction of a fatigue protocol was 60% greater in treated soleus muscles compared with contralateral control muscles (P < 0.05). Histopathology was not improved by PGC‐1α overexpression. Also, while there were numerous differences in gene expression between healthy and dystrophic muscle, there were relatively few differences between PGC‐1α‐treated limbs and contralateral control limbs. These data indicate that PGC‐1α pathway activation may interrupt the disease process even if initiated within the context of advanced disease; however, the mechanism that underlies this functional correction is not apparent.
Fatigue Analysis of a Point Absorber Wave Energy Converter Subjected to Passive and Reactive Control
Authors: Zurkinden A. S. , Lambertsen S. H. , Damkilde L. , Gao Z. , Moan T.
Published: August 2015

This paper investigates the effect of a passive and reactive control mechanism on the accumulated fatigue damage of a wave energy converter (WEC). Interest is focused on four structural details of the Wavestar arm, which is used as a case study here. The fatigue model is set up as an independent and generic toolbox, which can be applied to any other global response model of a WEC device combined with a control system. The stress responses due to the stochastic wave loads are computed by a finite element method (FEM) model using the frequency-domain approach. The fatigue damage is calculated based on the spectral-based fatigue analysis in which the fatigue is described by the given spectral moments of the stress response. The question will be discussed, which control case is more favorable regarding the tradeoff between fatigue damage reduction and increased power production.
Experimental Analysis and Microstructure Modeling of Friction Stir Extrusion of Magnesium Chips
Authors: Behnagh Reza Abdi , Shen Ninggang , Ansari Mohammad Ali , Narvan Morteza , Besharati Givi Mohammad Kazem , Ding Hongtao
Published: August 2015

In this work, the feasibility to recycle pure magnesium machining chips is first investigated experimentally with a solid-state recycling technique of friction stir extrusion (FSE). Heat generated from frictions among the stirring chips, die, and mold facilitates the extrusion process. Mechanical tests, optical microscopy (OM), and scanning electron microscopy (SEM) analysis are conducted to evaluate the mechanical and metallurgical properties of extruded wires. Mechanical tests show that almost all recycled specimens can achieve higher strength and elongation than original material of magnesium at room temperature. Due to a refined grain microstructure, good mechanical properties are obtained for samples produced by the rotational speed of 250 rpm and plunge rate of 14 mm/min. A metallo-thermo-mechanical coupled analysis is further conducted to understand the effects of process parameters. The analysis is carried out with a multistep two-dimensional (2D) coupled Eulerian–Lagrangian finite-element (FE) method using abaqus. The material constitutive model considers both work hardening and strain softening. Material grain size evolution is modeled by dynamic recrystallization (DRX) kinetics laws. The deformation process and its consequential microstructural attributes of grain size and microhardness are simulated. Physics principles of the microstructure evolution are discussed based on both experimental and numerical analyses.
Sensorless Force Sensing for Minimally Invasive Surgery
Authors: Zhao Baoliang , Nelson Carl A.
Published: August 2015

Robotic minimally invasive surgery (R-MIS) has achieved success in various procedures; however, the lack of haptic feedback is considered by some to be a limiting factor. The typical method to acquire tool–tissue reaction forces is attaching force sensors on surgical tools, but this complicates sterilization and makes the tool bulky. This paper explores the feasibility of using motor current to estimate tool-tissue forces and demonstrates acceptable results in terms of time delay and accuracy. This sensorless force estimation method sheds new light on the possibility of equipping existing robotic surgical systems with haptic interfaces that require no sensors and are compatible with existing sterilization methods.
Strength Criteria Versus Plastic Flow Criteria Used in Pressure Vessel Design and Analysis1
Authors: Zhu Xian-Kui
Published: August 2015

This paper presents a critical comparison of the traditional strength criteria and the modern plastic flow criteria used in the structural design and integrity assessment of pressure vessels. This includes (1) a brief review of the traditional strength criteria used in the ASME Boiler and Pressure Vessel (B&PV) Code, (2) a discussion of the shortcomings of the traditional strength criteria when used to predict the burst pressure of pressure vessels, (3) an analysis of challenges, technical gaps, and basic needs to improve the traditional strength criteria, (4) a comparison of strength theories and plasticity theories for ductile materials, (5) an evaluation of available plastic flow criteria and their drawbacks in prediction of burst pressure of pressure vessels, (6) a description of a newly developed multiaxial yield criterion and its application to pressure vessels, and (7) a demonstration of experimental validation of the new plastic flow criterion when used to predict the burst pressure of thin-wall pressure vessels. Finally, recommendations are made for further study to improve the traditional strength design criteria and to facilitate utilization of the modern plastic flow criteria for pressure vessel design and analysis.
ANCF Analysis of Textile Systems
Authors: Wang Liang , Wang Yongxing , Recuero Antonio M. , Shabana Ahmed A.
Published: August 2015

This paper presents a new flexible multibody system (MBS) approach for modeling textile systems including roll-drafting sets used in chemical textile machinery. The proposed approach can be used in the analysis of textile materials such as lubricated polyester filament bundles (PFBs), which have uncommon material properties best described by specialized continuum mechanics constitutive models. In this investigation, the absolute nodal coordinate formulation (ANCF) is used to model PFB as a hyperelastic transversely isotropic material. The PFB strain energy density function is decomposed into a fully isotropic component and an orthotropic, transversely isotropic component expressed in terms of five invariants of the right Cauchy–Green deformation tensor. Using this energy decomposition, the second Piola–Kirchhoff stress and the elasticity tensors can also be split into isotropic and transversely isotropic parts. The constitutive equations are used to define the generalized material forces associated with the coordinates of three-dimensional fully parameterized ANCF finite elements (FEs). The proposed approach allows for modeling the dynamic interaction between the rollers and PFB and allows for using spline functions to describe the PFB forward velocity. The paper demonstrates that the textile material constitutive equations and the MBS algorithms can be used effectively to obtain numerical solutions that define the state of strain of the textile material and the relative slip between the rollers and PFB.
A Multisite Study of Environmental Correlates of Active Commuting to School in Mexican Children
Authors: Jauregui Alejandra , Soltero Erica , Santos-Luna René , Hernández-Barrera Lucia , Barquera Simon , Jáuregui Edtna , Lévesque Lucie , López-Taylor Juan , Ortiz-Hernández Luis , Lee Rebecca
Published: August 2015

Background:

Mexican children often use active commuting to school (ACS). In order to maintain high levels of ACS it is important to understand correlates of ACS in this population. However, most evidence comes from high-income countries (HICs). We examined multilevel correlates of ACS in children attending public schools in 3 Mexican cities.

Methods:

Information on 1191 children (grades 3 to 5) attending 26 schools was retrieved from questionnaires, neighborhood audits, and geographic information systems data. Multilevel logistic modeling was used to explore individual and environmental correlates of ACS at 400-m and 800-m buffers surrounding schools.

Results:

Individual positive correlates for ACS included age (6–8 years vs 9–11 years, odds ratio [OR] = 1.5; 6–8 years vs ≥12 years: OR = 2.1) and ≥ 6 adults at home (OR = 2.0). At the 400-m buffer, more ACS was associated with lower walkability (OR = 0.87), presence of posted speed limits (< 6% vs > 12%: OR = 0.36) and crossing aids (< 6% vs 6–20%: OR = 0.25; > 20%: OR = 0.26), as well as higher sidewalk availability (< 70% vs > 90%: OR = 4.5). Similar relationships with speed limits and crossing aids were observed at the 800m buffer.

Conclusions:

Findings contrast with those reported in HICs, underscoring the importance of considering the local context when developing strategies to promote ACS. Future studies are needed to replicate these relationships and investigate the longitudinal impact of improving active transportation infrastructure and policies.
Associations Between Parental Perceptions of the Neighborhood Environment and Childhood Physical Activity: Results from ISCOLE-Kenya
Authors: Muthuri Stella K. , Wachira Lucy-Joy M. , Onywera Vincent O. , Tremblay Mark S.
Published: August 2015

Background:

A physical activity transition to declining activity levels, even among children, now poses a serious public health concern because of its contribution to a rising prevalence of noncommunicable diseases. Childhood physical activity levels are associated with parental perceptions of the neighborhood; however, these relationships have not been explored in sub-Saharan Africa (SSA). The objective was to investigate relationships between parental perceptions of the neighborhood and physical activity indicators among Kenyan children.

Methods:

Data were collected from children 9 to 11 years old in Nairobi as part of the International Study of Childhood Obesity, Lifestyle and Environment. Child physical activity was assessed by accelerometry, and information on obtaining sufficient physical activity, active transport, and parental perceptions of the neighborhood collected using questionnaires.

Results:

Of 563 participating children, 45.7%, 12.6%, and 11.4% used active school transportation, met physical activity guidelines, and were sufficiently active, respectively. Parental perception of positive neighborhood social cohesion, positive environs and connectivity, and negative child safety concerns, were associated with child physical activity outcomes.

Conclusions:

Aspects of parental perceptions of the neighborhood were associated with child physical activity outcomes and should be further explored to appropriately inform policy and practice in curbing declining physical activity levels among children in SSA.
The original social network
The Village Effect
Why Face-to-Face Contact Matters
Susan Pinker
Atlantic Books, 2015. 432 pp.
Authors: Wellman Barry
Published: August 2015

Forging personal connections in the digital age
Modified yeast produce opiates from sugar
Authors: Service Robert F.
Published: August 2015

Engineered microbes raise hopes for better medicines and concerns about illicit drugs.
Mashco Piro tribe emerges from isolation in Peru
Authors: Lawler Andrew
Published: August 2015

Crisis sparks debate about whether to make official contact or leave isolated tribespeople alone.
Nanomaterials in transistors: From high-performance to thin-film applications
Authors: Franklin Aaron D.
Published: August 2015

Improving transistors with nanomaterials

High-performance silicon transistors and thin-film transistors used in display technologies are fundamentally limited to miniaturization. Incorporating nanomaterials—such as carbon nanotubes, graphene, and related two-dimensional materials like molybdenum disulfide—into these devices as gate materials may circumvent some of these limitations. Franklin reviews the opportunities and challenges for incorporating nanomaterials into transistors to improve performance. Because high-performance transistors are distinct from thin-film transistors, incorporating them into flexible or transparent platforms raises new challenges.

Science
, this issue
10.1126/science.aab2750
Tumor angiogenesis, from foe to friend
Authors: Rivera Lee B. , Bergers Gabriele
Published: August 2015

Treatments that normalize or even promote blood vessel growth may enhance drug delivery to tumors
Comparison between Flow Cytometry, Microscopy, and Lactate Dehydrogenase-Based Enzyme-Linked Immunosorbent Assay for Plasmodium falciparum Drug Susceptibility Testing under Field Conditions
Authors: Woodrow Charles J. , Wangsing Chirapat , Sriprawat Kanlaya , Christensen Peter R. , Nosten Francois , Rénia Laurent , Russell Bruce , Malleret Benoît
Published: August 2015

Flow cytometry is an objective method for conducting
in vitro
antimalarial sensitivity assays with increasing potential for application in field sites. We examined
in vitro
susceptibility to seven anti-malarial drugs for 40 fresh
P. falciparum
field isolates via a flow cytometry method (FCM), a colorimetric LDH-based ELISA
(
DELI), and standard microscopic slide analysis of growth. For FCM, 184/280 (66%) assays met analytical acceptance criteria, compared to 166/280 (59%) for DELI. There was good agreement between FCM and microscopy, while DELI tended to produce higher half-maximal inhibition constants (IC
50
s) than FCM, with an overall bias of 2.2-fold (Bland-Altman comparison). Values for artesunate and dihydroartemisinin were most affected. Paradoxical increases in signal at very high concentrations of mefloquine and related compounds were more marked with the DELI assay, suggesting that off-target effects on LDH production may be responsible. Loss of FCM signal due to reinvasion or slow growth was observed in a small number of samples. These results extend previous work on use of flow cytometry to determine antimalarial susceptibility in terms of the number of samples, range of drugs, and comparison with other methods.
Characterization of Foodborne Outbreaks of Salmonella enterica Serovar Enteritidis with Whole-Genome Sequencing Single Nucleotide Polymorphism-Based Analysis for Surveillance and Outbreak Detection
Authors: Taylor Angela J. , Lappi Victoria , Wolfgang William J. , Lapierre Pascal , Palumbo Michael J. , Medus Carlota , Boxrud David
Published: August 2015

Salmonella enterica
serovar Enteritidis is a significant cause of gastrointestinal illness in the United States; however, current molecular subtyping methods lack resolution for this highly clonal serovar. Advances in next-generation sequencing technologies have made it possible to examine whole-genome sequencing (WGS) as a potential molecular subtyping tool for outbreak detection and source trace back. Here, we conducted a retrospective analysis of
S
. Enteritidis isolates from seven epidemiologically confirmed foodborne outbreaks and sporadic isolates (not epidemiologically linked) to determine the utility of WGS to identify outbreaks. A collection of 55 epidemiologically characterized clinical and environmental
S
. Enteritidis isolates were sequenced. Single nucleotide polymorphism (SNP)-based cluster analysis of the
S
. Enteritidis genomes revealed well supported clades, with less than four-SNP pairwise diversity, that were concordant with epidemiologically defined outbreaks. Sporadic isolates were an average of 42.5 SNPs distant from the outbreak clusters. Isolates collected from the same patient over several weeks differed by only two SNPs. Our findings show that WGS provided greater resolution between outbreak, sporadic, and suspect isolates than the current gold standard subtyping method, pulsed-field gel electrophoresis (PFGE). Furthermore, results could be obtained in a time frame suitable for surveillance activities, supporting the use of WGS as an outbreak detection and characterization method for
S
. Enteritidis.
Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication
Authors: Zhao Yongqian , Soh Tingjin Sherryl , Chan Kitti Wing Ki , Fung Sarah Suet Yin , Swaminathan Kunchithapadam , Lim Siew Pheng , Shi Pei-Yong , Huber Thomas , Lescar Julien , Luo Dahai , Vasudevan Subhash G.
Published: August 2015

We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication.
Increased Immune Response Variability during Simultaneous Viral Coinfection Leads to Unpredictability in CD8 T Cell Immunity and Pathogenesis
Authors: Kenney Laurie L. , Cornberg Markus , Chen Alex T. , Emonet Sebastien , de la Torre Juan Carlos , Selin Liisa K.
Published: August 2015

T cell memory is usually studied in the context of infection with a single pathogen in naive mice, but how memory develops during a coinfection with two pathogens, as frequently occurs in nature or after vaccination, is far less studied. Here, we questioned how the competition between immune responses to two viruses in the same naive host would influence the development of CD8 T cell memory and subsequent disease outcome upon challenge. Using two different models of coinfection, including the well-studied lymphocytic choriomeningitis (LCMV) and Pichinde (PICV) viruses, several differences were observed within the CD8 T cell responses to either virus. Compared to single-virus infection, coinfection resulted in substantial variation among mice in the size of epitope-specific T cell responses to each virus. Some mice had an overall reduced number of virus-specific cells to either one of the viruses, and other mice developed an immunodominant response to a normally subdominant, cross-reactive epitope (nucleoprotein residues 205 to 212, or NP205). These changes led to decreased protective immunity and enhanced pathology in some mice upon challenge with either of the original coinfecting viruses. In mice with PICV-dominant responses, during a high-dose challenge with LCMV clone 13, increased immunopathology was associated with a reduced number of LCMV-specific effector memory CD8 T cells. In mice with dominant cross-reactive memory responses, during challenge with PICV increased immunopathology was directly associated with these cross-reactive NP205-specific CD8 memory cells. In conclusion, the inherent competition between two simultaneous immune responses results in significant alterations in T cell immunity and subsequent disease outcome upon reexposure.

IMPORTANCECombination vaccines and simultaneous administration of vaccines are necessary to accommodate required immunizations and maintain vaccination rates. Antibody responses generally correlate with protection and vaccine efficacy. However, live attenuated vaccines also induce strong CD8 T cell responses, and the impact of these cells on subsequent immunity, whether beneficial or detrimental, has seldom been studied, in part due to the lack of known T cell epitopes to vaccine viruses. We questioned if the inherent increased competition and stochasticity between two immune responses during a simultaneous coinfection would significantly alter CD8 T cell memory in a mouse model where CD8 T cell epitopes are clearly defined. We show that some of the coinfected mice have sufficiently altered memory T cell responses that they have decreased protection and enhanced immunopathology when reexposed to one of the two viruses. These data suggest that a better understanding of human T cell responses to vaccines is needed to optimize immunization strategies.
Encapsidation of Host RNAs by Cucumber Necrosis Virus Coat Protein during both Agroinfiltration and Infection
Authors: Ghoshal Kankana , Theilmann Jane , Reade Ron , Maghodia Ajay , Rochon D'Ann
Published: August 2015

Next-generation sequence analysis of virus-like particles (VLPs) produced during agroinfiltration of cucumber necrosis virus (CNV) coat protein (CP) and of authentic CNV virions was conducted to assess if host RNAs can be encapsidated by CNV CP. VLPs containing host RNAs were found to be produced during agroinfiltration, accumulating to approximately 1/60 the level that CNV virions accumulated during infection. VLPs contained a variety of host RNA species, including the major rRNAs as well as cytoplasmic, chloroplast, and mitochondrial mRNAs. The most predominant host RNA species encapsidated in VLPs were chloroplast encoded, consistent with the efficient targeting of CNV CP to chloroplasts during agroinfiltration. Interestingly, droplet digital PCR analysis showed that the CNV CP mRNA expressed during agroinfiltration was the most efficiently encapsidated mRNA, suggesting that the CNV CP open reading frame may contain a high-affinity site or sites for CP binding and thus contribute to the specificity of CNV RNA encapsidation. Approximately 0.09% to 0.7% of the RNA derived from authentic CNV virions contained host RNA, with chloroplast RNA again being the most prominent species. This is consistent with our previous finding that a small proportion of CNV CP enters chloroplasts during the infection process and highlights the possibility that chloroplast targeting is a significant aspect of CNV infection. Remarkably, 6 to 8 of the top 10 most efficiently encapsidated nucleus-encoded RNAs in CNV virions correspond to retrotransposon or retrotransposon-like RNA sequences. Thus, CNV could potentially serve as a vehicle for horizontal transmission of retrotransposons to new hosts and thereby significantly influence genome evolution.

IMPORTANCE
Viruses predominantly encapsidate their own virus-related RNA species due to the possession of specific sequences and/or structures on viral RNA which serve as high-affinity binding sites for the coat protein. In this study, we show, using next-generation sequence analysis, that CNV also encapsidates host RNA species, which account for ∼0.1% of the RNA packaged in CNV particles. The encapsidated host RNAs predominantly include chloroplast RNAs, reinforcing previous observations that CNV CP enters chloroplasts during infection. Remarkably, the most abundantly encapsidated cytoplasmic mRNAs consisted of retrotransposon-like RNA sequences, similar to findings recently reported for flock house virus (A. Routh, T. Domitrovic, and J. E. Johnson, Proc Natl Acad Sci U S A 109:1907–1912, 2012). Encapsidation of retrotransposon sequences may contribute to their horizontal transmission should CNV virions carrying retrotransposons infect a new host. Such an event could lead to large-scale genomic changes in a naive plant host, thus facilitating host evolutionary novelty.
Enhanced Influenza Virus-Like Particle Vaccination with a Structurally Optimized RIG-I Agonist as Adjuvant
Authors: Beljanski Vladimir , Chiang Cindy , Kirchenbaum Greg A. , Olagnier David , Bloom Chalise E. , Wong Terianne , Haddad Elias K. , Trautmann Lydie , Ross Ted M. , Hiscott John
Published: August 2015

The molecular interaction between viral RNA and the cytosolic sensor RIG-I represents the initial trigger in the development of an effective immune response against infection with RNA viruses, resulting in innate immune activation and subsequent induction of adaptive responses. In the present study, the adjuvant properties of a sequence-optimized 5′-triphosphate-containing RNA (5′pppRNA) RIG-I agonist (termed M8) were examined in combination with influenza virus-like particles (VLP) (M8-VLP) expressing H5N1 influenza virus hemagglutinin (HA) and neuraminidase (NA) as immunogens. In combination with VLP, M8 increased the antibody response to VLP immunization, provided VLP antigen sparing, and protected mice from a lethal challenge with H5N1 influenza virus. M8-VLP immunization also led to long-term protective responses against influenza virus infection in mice. M8 adjuvantation of VLP increased endpoint and antibody titers and inhibited influenza virus replication in lungs compared with approved or experimental adjuvants alum, AddaVax, and poly(I·C). Uniquely, immunization with M8-VLP stimulated a T
H
1-biased CD4 T cell response, as determined by increased T
H
1 cytokine levels in CD4 T cells and increased IgG2 levels in sera. Collectively, these data demonstrate that a sequence-optimized, RIG-I-specific agonist is a potent adjuvant that can be utilized to increase the efficacy of influenza VLP vaccination and dramatically improve humoral and cellular mediated protective responses against influenza virus challenge.

IMPORTANCE
The development of novel adjuvants to increase vaccine immunogenicity is an important goal that seeks to improve vaccine efficacy and ultimately prevent infections that endanger human health. This proof-of-principle study investigated the adjuvant properties of a sequence-optimized 5′pppRNA agonist (M8) with enhanced capacity to stimulate antiviral and inflammatory gene networks using influenza virus-like particles (VLP) expressing HA and NA as immunogens. Vaccination with VLP in combination with M8 increased anti-influenza virus antibody titers and protected animals from lethal influenza virus challenge, highlighting the potential clinical use of M8 as an adjuvant in vaccine development. Altogether, the results describe a novel immunostimulatory agonist targeted to the cytosolic RIG-I sensor as an attractive vaccine adjuvant candidate that can be used to increase vaccine efficacy, a pressing issue in children and the elderly population.
The Breadth of Expandable Memory CD8
+
T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers
Authors: Ndhlovu Zaza M. , Stampouloglou Eleni , Cesa Kevin , Mavrothalassitis Orestes , Alvino Donna Marie , Li Jonathan Z. , Wilton Shannon , Karel Daniel , Piechocka-Trocha Alicja , Chen Huabiao , Pereyra Florencia , Walker Bruce D.
Published: August 2015

Previous studies have shown that elite controllers with minimal effector T cell responses harbor a low-frequency, readily expandable, highly functional, and broadly directed memory population. Here, we interrogated the
in vivo
relevance of this cell population by investigating whether the breadth of expandable memory responses is associated with the magnitude of residual viremia in individuals achieving durable suppression of HIV infection. HIV-specific memory CD8
+
T cells were expanded by using autologous epitopic and variant peptides. Viral load was measured by an ultrasensitive single-copy PCR assay. Following expansion, controllers showed a greater increase in the overall breadth of Gag responses than did untreated progressors (
P
= 0.01) as well as treated progressors (
P
= 0.0003). Nef- and Env-specific memory cells expanded poorly for all groups, and their expanded breadths were indistinguishable among groups (
P
= 0.9 for Nef as determined by a Kruskal-Wallis test;
P
= 0.6 for Env as determined by a Kruskal-Wallis test). More importantly, we show that the breadth of expandable, previously undetectable Gag-specific responses was inversely correlated with residual viral load (
r
= −0.6;
P
= 0.009). Together, these data reveal a direct link between the abundance of Gag-specific expandable memory responses and prolonged maintenance of low-level viremia. Our studies highlight a CD8
+
T cell feature that would be desirable in a vaccine-induced T cell response.

IMPORTANCE
Many studies have shown that the rare ability of some individuals to control HIV infection in the absence of antiretroviral therapy appears to be heavily dependent upon special HIV-specific killer T lymphocytes that are able to inhibit viral replication. The identification of key features of these immune cells has the potential to inform rational HIV vaccine design. This study shows that a special subset of killer lymphocytes, known as central memory CD8
+
T lymphocytes, is at least partially involved in the durable control of HIV replication. HIV controllers maintain a large proportion of Gag-specific expandable memory CD8
+
T cells involved in ongoing viral suppression. These data suggest that induction of this cell subset by future HIV vaccines may be important for narrowing possible routes of rapid escape from vaccine-induced CD8
+
T cell responses.