bluuebunny/crossref_metadata_2025 huggingface dataset:
A Structural Impairment Detection System Using Competitive Arrays of Artificial Neural Networks
Authors: Story Brett A. , Fry Gary T.
Published: August 2013

Impairments that occur in structural systems may degrade performance or prevent a structure from functioning safely. Detecting impairments prior to a structural failure reduces the effect of impairments on the safety of those using a structure. This article describes the computational framework of a Structural Impairment Detection System (SIDS) that processes the digital data streams of electronic sensors attached to critical components of a structure. The resulting system comprises a competitive array of neural networks that can accurately describe the types and severity of likely impairments present in the structure. The competitive array of neural networks is trained to detect patterns in data streams specific to likely target impairments. Data streams generated from ABAQUS models and from electronic sensors are used in training and evaluating the system. As part of the initial development of this SIDS, the counterweight truss of a 100‐year old railroad drawbridge was instrumented and evaluated. The resulting data streams were diagnosed autonomously by the SIDS as being similar to one of two operational conditions: unimpaired or a single impairment present in a member embedded within the counterweight. Further investigation of the counterweight truss is underway to verify the accuracy of the assessments.
Structural determinants stabilizing the axial channel of ClpP for substrate translocation
Authors: Alexopoulos John , Ahsan Bilal , Homchaudhuri Lopamudra , Husain Nabiha , Cheng Yi‐Qiang , Ortega Joaquin
Published: August 2013

Acyldepsipeptides (ADEPs) antibiotics bind to Escherichia coli ClpP mimicking the interactions that the IGL/F loops in ClpA or ClpX ATPases establish with the hydrophobic pockets surrounding the axial pore of the tetradecamer that the protease forms. ADEP binding induces opening of the gates blocking the axial channel of ClpP and allowing protein substrates to be translocated and hydrolysed in the degradation chamber. To identify the structural determinants stabilizing the open conformation of the axial channel for efficient substrate translocation, we constructed ClpP variants with amino acid substitutions in the N‐terminal region that forms the axial gates. We found that adoption of a β‐hairpin loop by this region and the integrity of the hydrophobic cluster at the base of this loop are necessary elements for the axial gate to efficiently translocate protein substrates. Analysis of ClpP variants from Bacillus subtilis suggested that the identified structural requirements of the axial channel for efficient translocation are conserved between Gram‐positive and Gram‐negative bacteria. These findings provide mechanistic insights into the activation of ClpP by ADEPs as well as the gating mechanism of the protease in the context of the ClpAP and ClpXP complexes.
Rice flooding negatively impacts root branching and arbuscular mycorrhizal colonization, but not fungal viability
Authors: VALLINO MARTA , FIORILLI VALENTINA , BONFANTE PAOLA
Published: August 2013

Understanding the mechanisms which regulate the symbiotic interactions between rice roots and the arbuscular mycorrizal (AM) fungi is becoming increasingly important in order to enhance plant yield in the context of sustainable agriculture. We have investigated the complex interactions among rice roots, AM symbiosis, and the environment focusing on the root development in flooding and upland conditions. Due to an experimental system where mycorrhizal rice plants can be moved from flooded to dry conditions and vice versa, and the use of morphological and molecular approaches, we conclusively demonstrated that the water regime is the driving force that decreases AM colonization under flooding conditions, by directly influencing root architecture (decreasing of large lateral roots) and anatomy (increasing of aerenchyma), but without impacting the basic AM functionality.
Skin temperature measurement using an infrared thermometer on patients who have been exposed to cold
Authors: Erenberk Ufuk , Torun Emel , Ozkaya Emin , Uzuner Selcuk , Demir Aysegul Dogan , Dundaroz Rusen
Published: August 2013

Backround

 The aim of this study was to determine if the skin temperature of febrile children is affected by the child's exposure to cold outdoor temperatures immediately prior to the taking of that temperature.

Methods

 A total of 150 febrile and non‐febrile children (aged 3–10 years) who had walked to the hospital's pediatric emergency department and were thus exposed to outside cold weather were enrolled in the study. Using infrared thermometry, forehead and chest skin temperatures were simultaneously measured every 2 min during the first 14 min after presentation. Temperatures were recorded and differences between the two measurements were calculated.

Results

 By the fifth evaluation (10 min from the first reading), skin temperatures from forehead and chest had equalized.

Conclusion

 Determination of fever from the body parts that had been exposed to cold environmental conditions may cause contradictory results if taken while the child is still chilled from exposure to the cold. For accuracy, children should be acclimated to the indoor temperature before taking body temperature readings. Acclimation takes at least 10 min after coming in from cold weather outside.
Photophysical Properties of Lanthanide (Eu3+, Tb3+) Hybrid Soft Gels of Double Functional Linker of Ionic Liquid–Modified Silane
Authors: Li Qiu‐Ping , Yan Bing
Published: August 2013

Four kinds of luminescent hybrid soft gels have been assembled by introducing the lanthanide (Eu3+, Tb3+) tetrakis β‐diketonate into the covalently bonded imidazolium‐based silica through electrostatic interactions. Here, the imidazolium‐based silica matrices are prepared from imidazolium‐derived organotriethoxysilanes by the sol–gel process, in which the imidazolium cations are strongly anchored within the silica matrices while anions can still be exchanged following application for functionalization of lanthanide complexes. The photoluminescence measurements indicated that these hybrid soft gels exhibit characteristic red and green luminescence originating from the corresponding ternary lanthanide ions (Eu3+, Tb3+). Further investigation of photophysical properties reveals that these soft gels have inherited the outstanding luminescent properties from the lanthanide tetrakis β‐diketonate complexes such as strong luminescence intensities, long lifetimes and high luminescence quantum efficiencies.
The influence of microgravity on Euglena gracilis as studied on Shenzhou 8
Authors: Nasir A. , Strauch S. M. , Becker I. , Sperling A. , Schuster M. , Richter P. R. , Weißkopf M. , Ntefidou M. , Daiker V. , An Y. A. , Li X. Y. , Liu Y. D. , Lebert M.
Published: August 2013

The German Aerospace Center (DLR) enabled German participation in the joint space campaign on the unmanned Shenzhou 8 spacecraft in November 2011. In this report, the effect of microgravity on Euglena gracilis cells is described. Custom‐made dual compartment cell fixation units (containing cells in one chamber and fixative – RNA lysis buffer – in another one) were enclosed in a small container and placed in the Simbox incubator, which is an experiment support system. Cells were fixed by injecting them with fixative at different time intervals. In addition to stationary experiment slots, Simbox provides a 1 g reference centrifuge. Cell fixation units were mounted in microgravity and 1 g reference positions of Simbox. Two Simbox incubators were used, one for space flight and the other as ground reference. Cells were fixed soon after launch and shortly before return of the spaceship. Due to technical problems, only early in‐flight samples (about 40 min after launch microgravity and corresponding 1 g reference) were fully mixed with fixative, therefore only data from those samples are presented. Transcription of several genes involved in signal transduction, oxidative stress defence, cell cycle regulation and heat shock responses was investigated with quantitative PCR. The data indicate that Euglena cells suffer stress upon short‐term exposure to microgravity; various stress‐induced genes were up‐regulated. Of 32 tested genes, 18 were up‐regulated, one down‐regulated and the rest remained unaltered. These findings are in a good agreement with results from other research groups using other organisms.
Information Acquisition and Voluntary Disclosure in an Export‐Processing System
Authors: Gao Long , Li Zhaolin , Shou Biying
Published: August 2013

We study a strategic information management problem in the export‐processing trade, where the buyer controls the raw material input and sales and the producer is responsible for production. The production is vulnerable to random yield risk. The producer can exert a costly effort to acquire the private yield rate information and discretionarily share it with the buyer. We develop a sequential Bayesian game model that captures three key features of the system—endogenous information endowment, voluntary disclosure, and ex post information sharing—a significant departure from the literature. The optimal disclosure strategy is driven by the trade‐off between the gains from Pareto efficiency improvement and self‐interested overproduction. It is specified by two thresholds on yield rate: only the middle‐yield producers (with yield rate between these two thresholds) share private information to improve supply‐demand match; the low‐ and high‐yield producers withhold information to extract excess input from the buyer. The buyer in response penalizes nondisclosure with reduced input and rewards information sharing with a larger order. This strategic interaction is further exacerbated by the double marginalization effect from decentralization, resulting in severe efficiency loss. We examine the effectiveness of three corrective mechanisms—vertical integration, mandatory disclosure, and production restriction—and reveal the costs of information suppressive effect and overinvestment incentive and the benefit from concessions on the processing fee. Our study endogenizes the asymmetric supply risk and provides the first attempt to rationalize the strategic interactions of informational and operational incentives in the export‐processing system.
Using Fairness Models to Improve Equity in Health Delivery Fleet Management
Authors: McCoy Jessica H. , Lee Hau L.
Published: August 2013

Inefficiency and inequity are two challenges that plague humanitarian operations and health delivery in resource‐limited regions. Increasing capacity in humanitarian and health delivery supply chains is one option that has the potential to improve equity while maintaining efficiency. For example, the nonprofit organization Riders for Health has worked to increase capacity by providing reliable transportation to health workers in rural parts of sub‐Saharan Africa; with more motorcycle hours at their disposal, health workers can perform more outreach to outlying communities. We develop a model using a family of fairness function to quantify the efficiency and equity of health delivery as capacity is increased via development programs. We present optimal resource allocations under utilitarian, proportionally fair, and egalitarian objectives and extend the model to include dual modes of transport and diminishing returns of subsequent outreach visits. Finally, we demonstrate how to apply our model at a regional level to provide support for humanitarian decision makers such as Riders for Health. We use data from the baseline phase of our evaluation trial of Riders for Health in Zambia to quantify efficiency and equity for one real‐world scenario.
Information Diffusion among Agents: Implications for Humanitarian Operations
Authors: Altay Nezih , Pal Raktim
Published: August 2013

The basis for this article is an information‐processing view of the UN's cluster approach. We use agent‐based modeling and simulations to show that clusters, if properly utilized, encourage better information flow and thus facilitate effective response to disasters. The article intends to turn the attention of the humanitarian community to the importance of sharing information and the role of cluster leads in facilitating humanitarian aid. Our results indicate that if cluster leads act as information hubs, information reaches its target faster, enabling a prompt humanitarian response. In addition, we show that information quality is critical for effective resource utilization—if cluster leads filter information, it moves faster. We also found evidence that the willingness to exchange information plays a larger role in transmitting information than that of an information hub, particularly during later stages of response operations.
Pricing and Operational Performance in Discretionary Services
Authors: Tong Chunyang , Rajagopalan Sampath
Published: August 2013

In many services, for example, website or landscape design, the value or quality derived by a customer depends upon the service time, and this valuation differs across customers. Customers procure the service based on the expected value to be delivered, prices charged, and the timeliness of service. We investigate the performance of the optimal pricing scheme as well as two commonly used pricing schemes (fixed fee and time‐based pricing) for such services on important dimensions such as revenue, demand served, and utilization. We propose a novel model that captures the above features and wherein both service rate and demand are endogenous and functions of the pricing scheme. In particular, service time is an outcome of the pricing scheme adopted and the heterogeneous valuations of customers, unlike in the queueing‐based pricing literature. We find that the service system may benefit from a greater variance in consumer valuations, and the performance of pricing schemes is impacted by the shape of the distribution of customers' valuation of service time and the responsiveness desired by customers. Both the fixed fee and time‐based schemes do well relative to the optimal pricing scheme in terms of revenue in many plausible scenarios, but there are substantial differences between the pricing schemes in some important operational metrics. For instance, the fixed fee scheme serves more customers and has higher utilization than the time‐based scheme. We also explore variants of the fixed and time‐based schemes that have better revenue performance and show that the two‐part tariff which is a combination of fixed and time‐based pricing can do as well as the optimal scheme in terms of revenue.
Integrality in Stochastic Inventory Models
Authors: Chen Wei , Dawande Milind , Janakiraman Ganesh
Published: August 2013

We study several finite‐horizon, discrete‐time, dynamic, stochastic inventory control models with integer demands: the newsvendor model, its multi‐period extension, and a single‐product, multi‐echelon assembly model. Equivalent linear programs are formulated for the corresponding stochastic dynamic programs, and integrality results are derived based on the total unimodularity of the constraint matrices. Specifically, for all these models, starting with integer inventory levels, we show that there exist optimal policies that are integral. For the most general single‐product, multi‐echelon assembly system model, integrality results are also derived for a practical alternative to stochastic dynamic programming, namely, rolling‐horizon optimization by a similar argument. We also present a different approach to prove integrality results for stochastic inventory models. This new approach is based on a generalization we propose for the one‐dimensional notion of piecewise linearity with integer breakpoints to higher dimensions. The usefulness of this new approach is illustrated by establishing the integrality of both the dynamic programming and rolling‐horizon optimization models of a two‐product capacitated stochastic inventory control system.
Improving Humanitarian Operations through Technology‐Enabled Collaboration
Authors: Ergun Özlem , Gui Luyi , Heier Stamm Jessica L. , Keskinocak Pinar , Swann Julie
Published: August 2013

Humanitarian supply chains involve many different entities, such as government, military, private, and non‐governmental organizations and individuals. Well‐coordinated interactions between entities can lead to synergies and improved humanitarian outcomes. Information technology (IT) tools can help facilitate collaboration, but cost and other barriers have limited their use. We document the use of an IT tool to improve last‐mile supply distribution and data management in one of many camps for internally displaced persons after the January 2010 earthquake in Haiti, and we describe other current uses of technology in camp management. Motivated by these examples and the interest among humanitarian organizations in expanding the use of such tools to facilitate coordination, we introduce a cooperative game theory model and explore insights about the conditions under which multi‐agency coordination is feasible and desirable. We also outline an agenda for future research in the area of technology‐enabled collaboration in the humanitarian sector.
Mesenteric fat thickness is associated with increased risk of obstructive sleep apnoea
Authors: Liu Kin Hung , Chu Winnie C.W. , To Kin Wang , Ko Fanny W.S. , Ng Susanna S.S. , Ngai Jenny C.L. , Chan Jeff Wai Sang , Ahuja Anil T. , Hui David S.C.
Published: August 2013

Background and objective

Mesenteric fat is a type of intraperitoneal adipose tissue draining into portal circulation. The objective of this study was to investigate the relationships between mesenteric fat thickness and obstructive sleep apnoea (OSA) in patients with suspected OSA.

Methods

One hundred forty‐nine subjects (men: 114; women: 35) with suspected OSA underwent ultrasound examinations of mesenteric, preperitoneal and subcutaneous fat thickness after overnight polysomnography. Body mass index (BMI) and neck circumference were recorded.

Results

The subjects with OSA (n = 130, apnoea/hypopnoea index (AHI) >5/h) had greater neck circumference, higher BMI, and greater mesenteric and preperitoneal fat thickness than those without OSA (n = 19, AHI ≤ 5/h). There was positive correlation of AHI with mesenteric (r = 0.43, P < 0.001) and preperitoneal fat thickness (r = 0.3, P < 0.001), whereas no significant association was observed between AHI and subcutaneous fat thickness (r = 0.09, P = 0.27). On multivariate logistic regression, after adjustments for gender, age, BMI, neck circumference, and preperitoneal and subcutaneous fat thickness, the mesenteric fat thickness had a positive association with the presence of moderate OSA and severe OSA, with odds ratios of 7.18 and 7.45 for every 1 cm increase in mesenteric fat thickness when AHI was defined as ≥15/h and AHI ≥ 30/h, respectively.

Conclusions

Mesenteric fat thickness is associated with increased risk of OSA, independent of other abdominal fat thickness, BMI and neck circumference. Sonographic measurement is potentially a useful tool for further evaluating the complex association of visceral fat, metabolic syndrome and OSA.
Closing the Wealth Gap: A Review of Racial and Ethnic Inequalities in Homeownership
Authors: Kuebler Meghan
Published: August 2013

Homeownership plays an important role in the socioeconomic well‐being of Americans. Despite recent major losses in wealth due to the subprime market crash, home equity remains the largest source of wealth for the average American family. A marker of class status, owning one's home provides access to neighborhoods with the best schools, quality public services, and lowest crime. This article demonstrates that minorities have not had the same access to homeownership that Whites have, and this contributes to continuing socioeconomic disparities between Whites and minorities. This article explores the homeownership experience of Blacks – including African‐Americans, Caribbeans, and Africans – Hispanics, and Asians in the United States relative to non‐Hispanic Whites. Minorities rely heavily on homeownership and home equity as the key component of their wealth and remain less likely than Whites to hold alternative forms of investment such as stocks. The role that homeownership plays in perpetuating intergenerational wealth disparities between Whites and minorities is discussed as are challenges to minority homeownership such as the pervasiveness of risky mortgage products. Exploring the racial gap in homeownership is fundamental to understanding racial inequalities and formulating strategies and policies to help close such disparities. This article concludes with suggestions for future research.
Racialization and Muslims: Situating the Muslim Experience in Race Scholarship
Authors: Selod Saher , Embrick David G.
Published: August 2013

This article reviews how racialization enables an understanding of Muslim and Muslim American experience as racial. Race scholarship in the United States has historically been a Black/White paradigm. As a result, the experiences of many racial and ethnic groups who have become a part of the American landscape due to the passage of the Immigration and Nationality Act of 1965 have largely been ignored in race scholarship. By reviewing racialization and its application to Arabs and Muslims, it is apparent that scholars must continuously explore newer theories and languages of race. Racialization not only provides a way to understand the fluidity of race and racism but it also contributes to the advancement of race scholarship by reflecting on the current contextual influences on race.
Associations Between Behavioral Inhibition and Children's Social Problem‐solving Behavior During Social Exclusion
Authors: Walker Olga L. , Henderson Heather A. , Degnan Kathryn A. , Penela Elizabeth C. , Fox Nathan A.
Published: August 2013

The current study examined the associations between the early childhood temperament of behavioral inhibition and children's displays of social problem‐solving (SPS) behavior during social exclusion. During toddlerhood (the ages of two to three), maternal report and behavioral observations of behavioral inhibition were collected. At the age of seven, children's SPS behaviors were observed during a laboratory social exclusion task based on the commonly used Cyberball game. Results showed that behavioral inhibition was positively associated with displayed social withdrawal and negatively associated with assertive behavior during the observed social exclusion task at seven years of age. These results add to our understanding of inhibited children's SPS behaviors during social exclusion and provide evidence for the associations between toddler temperament and children's social behavior during middle childhood.
Soil structural degradation in SW England and its impact on surface‐water runoff generation
Authors: Palmer R. C. , Smith R. P.
Published: August 2013

Field investigations between 2002 and 2011 identified soil structural degradation to be widespread in SW England with 38% of the 3243 surveyed sites having sufficiently degraded soil structure to produce observable features of enhanced surface‐water runoff within the landscape. Soil under arable crops often had high or severe levels of structural degradation. Late‐harvested crops such as maize had the most damaged soil where 75% of sites were found to have degraded structure generating enhanced surface‐water runoff. Soil erosion in these crops was found at over one in five sites. A tendency for the establishment of winter cereals in late autumn in the South West also often resulted in damaged soil where degraded structure and enhanced surface‐water runoff were found in three of every five cereal fields. Remedial actions to improve soil structure are either not being undertaken or are being unsuccessfully used. Brown Sands, Brown Earths and loamy Stagnogley Soils were the most frequently damaged soils. The intensive use of well‐drained, high quality sandy and coarse loamy soils has led to soil structural damage resulting in enhanced surface‐water runoff from fields that should naturally absorb winter rain. Surface water pollution, localized flooding and reduced winter recharge rates to aquifers result from this damage. Chalk and limestone landscapes on the other hand show little evidence of serious soil structural degradation and <20% of fields in these landscapes generate enhanced runoff.
Autologous skin substitute for hard‐to‐heal ulcers: Retrospective analysis on safety, applicability, and efficacy in an outpatient and hospitalized setting
Authors: Blok Chantal S. , Vink Liselot , de Boer Edith M. , van Montfrans Catherine , van den Hoogenband Henk M. , Mooij Michael C. , Gauw Stefanie A. , Vloemans Jos A. F. P. M , Bruynzeel Ineke , van Kraan Aleid , Kuik Joop , Waaijman Taco , Scheper Rik J. , Gibbs Susan
Published: August 2013

Chronic ulcers ((arterio)venous, decubitus, or postoperative) have no tendency to heal within a period of at least 3 months despite optimal therapy according to internationally accepted guidelines. This retrospective study evaluates the safety and efficacy of an autologous, dermal‐epidermal skin substitute (SS) for treating ulcers of various origins. Ulcers were treated within 7 Dutch centers over 5 years. Sixty‐six ulcers (size: 0.75–150 cm2; duration: 0.25–32 years) with a follow‐up time of 24 weeks after a single‐skin substitute application were assessed. Wound‐bed preparation consisted of vacuum‐assisted‐closure‐therapy (5 days, hospitalized) or application of acellular dermis (5–7 days, outpatient). Time to heal, adverse events, and recurrence 1 year after complete healing were recorded. Complete ulcer healing occurred in 36 of 66 ulcers (55%) at 24 weeks. At that time point, a further 29% of ulcers showed decrease in ulcer size between 50 and 99%. No difference was observed between the hospitalized vs. outpatient treatment with complete healing. There were 32 of 36 healed ulcers that were available for follow‐up 1 year after complete closure, of which 27 (84%) were still closed. Only two minor/moderate possibly related adverse events were recorded. This retrospective analysis shows that SS provides a safe and successful treatment for particularly chronic ulcers of various origins.
A Quantum Many-Body Spin System in an Optical Lattice Clock
Authors: Martin M. J. , Bishof M. , Swallows M. D. , Zhang X. , Benko C. , von-Stecher J. , Gorshkov A. V. , Rey A. M. , Ye Jun
Published: August 2013

Strongly Correlated Clocks

Optical lattice clocks with alkaline earth atoms provide one of the most stable time-keeping systems. Such clocks, in general, exhibit shifts in their transition frequencies as a consequence of interactions between atoms. Can this sensitivity be used to explore the dynamics of strongly correlated quantum systems?

Martin
et al.

(p.
632
) used a 1-dimensional optical lattice clock to study quantum many-body effects. Whereas the clock shift itself could be modeled within the mean field approximation, quantities such as spin noise required a full many-body treatment. This system may be useful for the quantum simulation of exotic magnetism.
Technical Comment on “The Placental Mammal Ancestor and the Post–K-Pg Radiation of Placentals”
Authors: Springer Mark S. , Meredith Robert W. , Teeling Emma C. , Murphy William J.
Published: August 2013

O’Leary
et al
. (Research Article, 8 February 2013, p. 662) examined mammalian relationships and divergence times and concluded that a single placental ancestor crossed the Cretaceous-Paleogene (K-Pg) boundary. This conclusion relies on phylogenetic analyses that fail to discriminate between homology and homoplasy and further implies virus-like rates of nucleotide substitution in early Paleocene placentals.
Buildings as Weapons of Mass Destruction
Authors: Bilham Roger , Gaur Vinod
Published: August 2013

The enforcement of sound building practices would substantially reduce future fatalities from earthquakes in south central Asia.
Critics Skeptical as Flu Scientists Argue for Controversial H7N9 Studies
Authors: Malakoff David
Published: August 2013

Avian flu researchers argue for controversial experiments with H7N9, but critics are skeptical.
House Subpoena Revives Battle Over Air Pollution Studies
Authors: Servick Kelly
Published: August 2013

The House science committee has subpoenaed EPA for data underlying key air pollution studies, raising concerns about subject confidentiality.
The Web's Faceless Judges
Authors: Couzin-Frankel Jennifer
Published: August 2013

PubPeer is the latest forum for free-ranging discussion of published papers. It can only succeed, say its anonymous founders, if participants are able to keep their identities hidden.
Modified Opsonization, Phagocytosis, and Killing Assays To Measure Potentially Protective Antibodies against Pneumococcal Surface Protein A
Authors: Daniels Calvin C. , Kim Kyung-Hyo , Burton Robert L. , Mirza Shaper , Walker Melissa , King Janice , Hale Yvette , Coan Patricia , Rhee Dong-Kwon , Nahm Moon H. , Briles David E.
Published: August 2013

The standard opsonophagocytosis killing assay (OPKA) for antibodies to pneumococcal capsular polysaccharide was modified to permit an evaluation of the protection-mediating antibodies to pneumococcal surface protein A (PspA). We found that by increasing the incubation time with the complement and phagocytes from 45 min to 75 min, the protective activity was readily detected. In another modification, we used a capsule type 2 target strain that expressed PspA but not pneumococcal surface protein C (PspC). With these modifications separately or in combination, rabbit antisera to the recombinant α-helical or proline-rich domains of PspA mediated >50% killing of the target strain. The ability of normal human sera to mediate the killing of pneumococci in this modified OPKA correlated with their levels of antibodies to PspA and their ability to protect mice against fatal infection with a type 3 strain. Passive protection of mice against pneumococci and killing in the modified OPKA were lost when normal human sera were adsorbed with recombinant PspA (rPspA) on Sepharose, thus supporting the potential utility of the modified OPKA to detect protective antibodies to PspA. In the standard OPKA, monoclonal antibodies to PspA were strongly protective in the presence of subprotective amounts of anti-capsule. Thus, the currently established high-throughput OPKA for antibodies to capsule could be modified in one of two ways to permit an evaluation of the opsonic efficacy of antibodies to PspA.
Subcutaneous Administration of a 10-Fold-Lower Dose of a Commercial Human Tuberculosis Vaccine, Mycobacterium bovis Bacillus Calmette-Guérin Danish, Induced Levels of Protection against Bovine Tuberculosis and Responses in the Tuberculin Intradermal Test Similar to Those Induced by a Standard Cattle Dose
Authors: Buddle Bryce M. , Hewinson R. Glyn , Vordermeier H. Martin , Wedlock D. Neil
Published: August 2013

Vaccination of cattle with a commercial human tuberculosis (TB) vaccine,Mycobacterium bovisbacillus Calmette-Guérin (BCG) Danish, at a dose equivalent to 5 human doses of BCG has protected these animals against TB in field and experimental trials. There is interest in determining whether a 10-fold-lower dose could still protect cattle but not induce a tuberculin intradermal test response. Two groups of calves (n= 9/group) were vaccinated subcutaneously with a lyophilized BCG Danish vaccine containing either 0.5 (1 × 105to 4 × 105CFU) or 5 (1 × 106to 4 × 106CFU) human doses of BCG Danish, with an additional group of 10 calves serving as nonvaccinated controls. Fifteen weeks after vaccination, these animals were challenged intratracheally with 5 × 103CFU of virulentM. bovisand another 15 weeks later were slaughtered and examined for the presence of tuberculous lesions. Vaccination of the calves with either 0.5 or 5 equivalent human doses of BCG Danish induced similar levels of protection against challenge withM. bovis, with both groups showing significant reductions in the pathological and microbiological parameters compared to those for the the control group (P< 0.05). Vaccination with either of the two BCG doses induced similar numbers of animals responding to the tuberculin intradermal test at 11 weeks postvaccination. Vaccination with a 0.5 equivalent human dose of a commercial lyophilized BCG vaccine can protect cattle against challenge withM. bovis.
The Golgi Protein ACBD3, an Interactor for Poliovirus Protein 3A, Modulates Poliovirus Replication
Authors: Téoulé François , Brisac Cynthia , Pelletier Isabelle , Vidalain Pierre-Olivier , Jégouic Sophie , Mirabelli Carmen , Bessaud Maël , Combelas Nicolas , Autret Arnaud , Tangy Frédéric , Delpeyroux Francis , Blondel Bruno
Published: August 2013

We have shown that the circulating vaccine-derived polioviruses responsible for poliomyelitis outbreaks in Madagascar have recombinant genomes composed of sequences encoding capsid proteins derived from poliovaccine Sabin, mostly type 2 (PVS2), and sequences encoding nonstructural proteins derived from other human enteroviruses. Interestingly, almost all of these recombinant genomes encode a nonstructural 3A protein related to that of field coxsackievirus A17 (CV-A17) strains. Here, we investigated the repercussions of this exchange, by assessing the role of the 3A proteins of PVS2 and CV-A17 and their putative cellular partners in viral replication. We found that the Golgi protein acyl-coenzyme A binding domain-containing 3 (ACBD3), recently identified as an interactor for the 3A proteins of several picornaviruses, interacts with the 3A proteins of PVS2 and CV-A17 at viral RNA replication sites, in human neuroblastoma cells infected with either PVS2 or a PVS2 recombinant encoding a 3A protein from CV-A17 [PVS2-3A(CV-A17)]. The small interfering RNA-mediated downregulation of ACBD3 significantly increased the growth of both viruses, suggesting that ACBD3 slowed viral replication. This was confirmed with replicons. Furthermore, PVS2-3A(CV-A17) was more resistant to the replication-inhibiting effect of ACBD3 than the PVS2 strain, and the amino acid in position 12 of 3A was involved in modulating the sensitivity of viral replication to ACBD3. Overall, our results indicate that exchanges of nonstructural proteins can modify the relationships between enterovirus recombinants and cellular interactors and may thus be one of the factors favoring their emergence.
Limited Nucleotide Changes in the Rev Response Element (RRE) during HIV-1 Infection Alter Overall Rev-RRE Activity and Rev Multimerization
Authors: Sloan Emily A. , Kearney Mary F. , Gray Laurie R. , Anastos Kathryn , Daar Eric S. , Margolick Joseph , Maldarelli Frank , Hammarskjold Marie-Louise , Rekosh David
Published: August 2013

HIV-1 Rev and the Rev response element (RRE) enable a critical step in the viral replication cycle by facilitating the nuclear export of intron-containing mRNAs, yet their activities have rarely been analyzed in natural infections. This study characterized their genetic and functional variation in a small cohort of HIV-infected individuals. Multiple Rev and RRE sequences were obtained using single-genome sequencing (SGS) of plasma samples collected within 6 months after seroconversion and at a later time. This allowed the identification of cognate sequences that were linked
in vivo
in the same viral genome and acted together as a functional unit. Phylogenetic analyses of these sequences indicated that 4/5 infections were founded by a single transmission event. Rev and RRE variants from each time point were subjected to functional analysis as both cognate pairs and as individual components. While a range of Rev-RRE activities were seen, the activity of cognate pairs from a single time point clustered to a discrete level, which was termed the set point. In 3/5 patients, this set point changed significantly over the time period studied. In all patients, RRE activity was more sensitive to sequence variation than Rev activity and acted as the primary driver of the cognate set point. Selected patient RREs were also shown to have differences in Rev multimerization using gel shift binding assays. Thus, rather than acting as a simple on-off switch or maintaining a constant level of activity throughout infection, the Rev-RRE system can fluctuate, presumably to control replication.
Compensatory Hemagglutinin Mutations Alter Antigenic Properties of Influenza Viruses
Authors: Myers Jaclyn L. , Wetzel Katherine S. , Linderman Susanne L. , Li Yang , Sullivan Colleen B. , Hensley Scott E.
Published: August 2013

Influenza viruses routinely acquire mutations in antigenic sites on the globular head of the hemagglutinin (HA) protein. Since these antigenic sites are near the receptor binding pocket of HA, many antigenic mutations simultaneously alter the receptor binding properties of HA. We previously reported that a K165E mutation in the Sa antigenic site of A/Puerto Rico/8/34 (PR8) HA is associated with secondary neuraminidase (NA) mutations that decrease NA activity. Here, using reverse genetics, we show that the K165E HA mutation dramatically decreases HA binding to sialic acid receptors on cell surfaces. We sequentially passaged reverse-genetics-derived PR8 viruses with the K165E antigenic HA mutation in fertilized chicken eggs, and to our surprise, viruses with secondary NA mutations did not emerge. Instead, viruses with secondary HA mutations emerged in 3 independent passaging experiments, and each of these mutations increased HA binding to sialic acid receptors. Importantly, these compensatory HA mutations were located in the Ca antigenic site and prevented binding of Ca-specific monoclonal antibodies. Taken together, these data indicate that HA antigenic mutations that alter receptor binding avidity can be compensated for by secondary HA or NA mutations. Antigenic diversification of influenza viruses can therefore occur irrespective of direct antibody pressure, since compensatory HA mutations can be located in distinct antibody binding sites.
Subviral Dense Bodies of Human Cytomegalovirus Stimulate Maturation and Activation of Monocyte-Derived Immature Dendritic Cells
Authors: Sauer Caroline , Klobuch Sebastian , Herr Wolfgang , Thomas Simone , Plachter Bodo
Published: August 2013

Dendritic cells play a central role in the immune control of human cytomegalovirus (HCMV) infection. This work aimed at investigating the impact of noninfectious, subviral dense bodies of HCMV on the maturation and activation of dendritic cells (DC). Treatment of immature DC with dense bodies led to the maturation of these cells and significantly increased their capacity for cytokine release and antigen presentation. Dense body-activated DC may thereby contribute to the development of antiviral immunity.
Cytomegalovirus Vaccine Strain Towne-Derived Dense Bodies Induce Broad Cellular Immune Responses and Neutralizing Antibodies That Prevent Infection of Fibroblasts and Epithelial Cells
Authors: Cayatte Corinne , Schneider-Ohrum Kirsten , Wang Zhaoti , Irrinki Alivelu , Nguyen Nga , Lu Janine , Nelson Christine , Servat Esteban , Gemmell Lorraine , Citkowicz Andrzej , Liu Yi , Hayes Gregory , Woo Jennifer , Van Nest Gary , Jin Hong , Duke Gregory , McCormick A. Louise
Published: August 2013

Human cytomegalovirus (HCMV), a betaherpesvirus, can cause severe disease in immunosuppressed patients and following congenital infection. A vaccine that induces both humoral and cellular immunity may be required to prevent congenital infection. Dense bodies (DBs) are complex, noninfectious particles produced by HCMV-infected cells and may represent a vaccine option. As knowledge of the antigenicity and immunogenicity of DB is incomplete, we explored characterization methods and defined DB production methods, followed by systematic evaluation of neutralization and cell-mediated immune responses to the DB material in BALB/c mice. DBs purified from Towne-infected cultures treated with the viral terminase inhibitor 2-bromo-5,6-dichloro-1-beta-
d
-ribofuranosyl benzimidazole riboside (BDCRB) were characterized by nanoparticle tracking analysis (NTA), two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), immunoblotting, quantitative enzyme-linked immunosorbent assay, and other methods. The humoral and cellular immune responses to DBs were compared to the immunogenicity of glycoprotein B (gB) administered with the adjuvant AddaVax (gB/AddaVax). DBs induced neutralizing antibodies that prevented viral infection of cultured fibroblasts and epithelial cells and robust cell-mediated immune responses to multiple viral proteins, including pp65, gB, and UL48. In contrast, gB/AddaVax failed to induce neutralizing antibodies that prevented infection of epithelial cells, highlighting a critical difference in the humoral responses induced by these vaccine candidates. Our data advance the potential for the DB vaccine approach, demonstrate important immunogenicity properties, and strongly support the further evaluation of DBs as a CMV vaccine candidate.
A Viral Histone H4 Joins to Eukaryotic Nucleosomes and Alters Host Gene Expression
Authors: Hepat Rahul , Song Ji-Joon , Lee Daeweon , Kim Yonggyun
Published: August 2013

A viral histone H4 (CpBV-H4) is encoded in a polydnavirus,Cotesia plutellaebracovirus. Its predicted amino acid sequence is highly homologous to that of host insect histone H4 except for an extended N-terminal tail containing 38 amino acids with nine lysine residues. Its expression induces an immunosuppression of target insects by suppressing immune-associated genes, presumably through an epigenetic control. This study analyzed its molecular interaction with eukaryotic host nucleosomes and subsequent regulation of host gene expression. Purified recombinant CpBV-H4 could associate with nucleosomal components (H2A, H2B, H3, and H4) and form an octamer. Transient expression of CpBV-H4 in an insect,Tribolium castaneum, was performed by microinjection of a recombinant expression vector and confirmed by both reverse transcriptase PCR (RT-PCR) and immunoblotting assays. Under this transient expression condition, total RNAs were extracted and read by a deep-sequencing technique. Annotated transcripts were classified into different gene ontology (GO) categories and compared with those of control insects injected with a truncated CpBV-H4. Target genes manipulated by CpBV-H4 expression showing significant differences (fold changes > 109) included all GO categories, including development and immune-associated genes. When the target genes were physically mapped, they were found to be scattered on entire chromosomes ofT. castaneum. In addition, chromatin immunoprecipitation against CpBV-H4 determined 16 nucleosome sites (P< 10−5) of the viral histone incorporation, which were noncoding regions near DNA-binding and inducible genes. These findings suggest that the viral histone H4 alters host gene expression by a direct molecular interaction with insect nucleosomes.
6-O- andN-Sulfated Syndecan-1 Promotes Baculovirus Binding and Entry into Mammalian Cells
Authors: Makkonen Kaisa-Emilia , Turkki Paula , Laakkonen Johanna P. , Ylä-Herttuala Seppo , Marjomäki Varpu , Airenne Kari J.
Published: August 2013

Baculoviruses are insect-specific viruses commonly found in nature. They are not able to replicate in mammalian cells but can transduce them when equipped with an appropriate mammalian cell active expression cassette. Although the viruses have been studied in several types of mammalian cells from different origins, the receptor that baculovirus uses to enter or interact with mammalian cells has not yet been identified. Due to the wide tropism of the virus, the receptor has been suggested to be a generally found cell surface molecule. In this article, we investigated the interaction of baculovirus and mammalian cell surface heparan sulfate proteoglycans (HSPG) in more detail. Our data show that baculovirus requires HSPG sulfation, particularlyN- and 6-O-sulfation, to bind to and transduce mammalian cells. According to our results, baculovirus binds specifically to syndecan-1 (SDC-1) but does not interact with SDC-2 to SDC-4 or with glypicans. Competition experiments performed with SDC-1 antibody or recombinant SDC-1 protein inhibited baculovirus binding, and SDC-1 overexpression enhanced baculovirus-mediated transduction. In conclusion, we show that SDC-1, a commonly found cell surface HSPG molecule, has a role in the binding and entry of baculovirus in vertebrate cells. The results presented here reveal important aspects of baculovirus entry and can serve as a basis for next-generation baculovirus vector development for gene delivery.
Mov10 and APOBEC3G Localization to Processing Bodies Is Not Required for Virion Incorporation and Antiviral Activity
Authors: Izumi Taisuke , Burdick Ryan , Shigemi Mayu , Plisov Sergey , Hu Wei-Shau , Pathak Vinay K.
Published: August 2013

Mov10 and APOBEC3G (A3G) localize to cytoplasmic granules called processing bodies (P bodies), incorporate into human immunodeficiency virus type 1 (HIV-1) virions, and inhibit viral replication. The functional relevance of Mov10/A3G P-body localization to virion incorporation and antiviral activity has not been fully explored. We found that a helicase V mutant of Mov10 exhibits significantly reduced localization to P bodies but still efficiently inhibits viral infectivity via virion incorporation. Disruption of the P bodies by DDX6 knockdown also confirmed Mov10 antiviral activity without P-body localization. In addition, overexpression of SRP19, which binds to 7SL RNA, depleted A3G from P bodies but did not affect its virion incorporation. Sucrose gradient sedimentation assays revealed that the majority of Mov10, A3G, HIV-1 RNA, and Gag formed high-molecular-mass (HMM) complexes that are converted to low-molecular-mass (LMM) complexes after RNase A treatment. In contrast, the P-body markers DCP2, LSM1, eIF4e, DDX6, and AGO1 were in LMM complexes, whereas AGO2, an effector protein of the RNA-induced silencing complex that localizes to P bodies, was present in both LMM and HMM complexes. Depletion of AGO2 indicated that RNA-induced silencing function is required for Mov10's ability to reduce Gag expression upon overexpression, but not its virion incorporation or effect on virus infectivity. We conclude that the majority of Mov10 and A3G are in HMM complexes, whereas most of the P-body markers are in LMM complexes, and that virion incorporation and the antiviral activities of Mov10 and A3G do not require their localization to P bodies.
Tattoo pigment in axillary lymph node mimicking calcification of breast cancer
Authors: Matsika Admire , Srinivasan Bhuvana , Gray Janet Meryl , Galbraith Christine Ruth
Published: August 2013

A tattoo is defined as the intentional or accidental deposit of pigment into the skin. The phenomenon of skin tattooing is on the rise worldwide and complications of tattooing are increasingly being recognised in diagnostic and clinical medicine. We describe a case of calcification-like changes on mammography resembling that of breast malignancy as a result of tattoo pigment deposition in an axillary lymph node. Recognition of such changes in routine breast screening is crucial to avoid further unnecessary invasive investigations and surgery in such patients.
Should anyone still be taking simvastatin 80 mg?
Authors: Tayal Upasana , Carroll Richard
Published: August 2013

A 64-year-old woman who previously suffered myalgia with lower dose simvastatin was given just one high dose of simvastatin and developed rhabdomyolysis. This was a potentially life-threatening complication. Fortunately she recovered with conservative management and did not require haemofiltration. This case reminds us of the risks of statins and the caution that needs to be exercised when prescribing these medications to patients with a history of intolerances.