bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of an Ultrasound Imaging Technique of the Tympanic Bullae for the Diagnosis of Otitis Media in Calves
Authors: Bernier Gosselin V. , Babkine M. , Gains M.J. , Nichols S. , Arsenault J. , Francoz D.
Published: July 2014

Background

Otitis media is a common disease in calves that can be subclinical, making antemortem on‐farm diagnosis challenging.

Objectives

To evaluate the sensitivity and specificity of ultrasonography of tympanic bullae for the diagnosis of clinical and subclinical otitis media and to evaluate the reproducibility of the technique.

Animals

Forty calves 19–50 days of age were selected from a veal calf farm.

Methods

Prospective study. Ultrasonography was first performed on the farm by ultrasonographer A (US A). Ultrasonography was repeated by ultrasonographer A (US A') and another ultrasonographer (US B) at the Centre Hospitalier Universitaire Vétérinaire. Images were later reread by both examiners and a diagnosis was recorded. The calves were euthanized and submitted for necropsy, and histopathologic diagnosis was used as the gold standard.

Results

Forty‐five bullae were affected by otitis media and 35 bullae were normal. Sensitivity and specificity of the ultrasound technique ranged from 32 to 63% and 84 to 100%, respectively, depending on the examiner and classification of suspicious ultrasonography results. Kappa analysis to evaluate interobserver agreement between A' and B yielded a к value of 0.53. Agreement within the same examiner (A versus A') yielded a к value of 0.48, and real‐time ultrasound versus rereading of recorded images for A' and B yielded к values of 0.58 and 0.75, respectively.

Conclusions

Sensitivity and specificity of the ultrasound imaging technique are, respectively, low and high for diagnosis of clinical and subclinical otitis media in calves, with moderate reproducibility.
Seeing through the skin: dermal light sensitivity provides cryptism in moorish gecko
Authors: Fulgione D. , Trapanese M. , Maselli V. , Rippa D. , Itri F. , Avallone B. , Van Damme R. , Monti D. M. , Raia P.
Published: July 2014

Concealment by means of colour change is a pre‐eminent deceptive mechanism used by both predators and prey. The moorish gecko Tarentola mauritanica is able to blend into the background by either darkening or paling according to the substrate darkness. Here we examined the functioning of background perception in moorish gecko. We experimentally excluded the involvement of melanophore‐stimulating hormone in camouflage. Blindfolded individuals change their colour consistently with the background. Surprisingly, individuals with covered flanks were not able to change colour, no matter whether they were allowed to see the substrate or not. Accordingly, we found high levels of opsin transcript and protein in the flank region of the gecko. These observations suggest that T. mauritanica skin melanophores are able to activate a process of colour change autonomously. This study yields the first evidence of crypsis mediated by dermal light sensitivity in amniotes.
The Wage Gap against Gay Men: The Leveling of the Playing Field
Authors: Elmslie Bruce , Tebaldi Edinaldo
Published: July 2014

This study uses data from the March Supplement Current Population Survey (CPS) to examine the wage differential against gay men from 1995 to 2011 in the United States. A wage equation is estimated using the Heckman two‐stage method, which addresses the sample selection bias inherent in wage equation estimations. We find evidence that in the United States the wage gap against gay men has significantly decreased over the last two decades. We also find that evidence that the wage gap has become concentrated in three occupations: managerial, sales, and protective services. We conclude that the evidence is most consistent with the hypothesis that discrimination is decreasing, and possibly non‐existent and that any lingering discrimination is based on the taste for discrimination by employees against being managed by a gay man and by customers.
Needs‐Based Targeting or Favoritism? The Regional Allocation of Multilateral Aid within Recipient Countries
Authors: Öhler Hannes , Nunnenkamp Peter
Published: July 2014

The regional allocation of aid within recipient countries has been largely ignored. We use geocoded data on the location of aid projects financed by the World Bank and the African Development Bank within a sample of 27 recipient countries to assess the claim of donors that their aid targets needy population segments. We also assess whether political leaders in these countries direct aid funds to their home region. We do not find that the multilateral institutions take regional needs into account. Instead, favoritism appears to play an important role for location choices, in particular for physical infrastructure projects.
Crusading Gone Global? The Icelandic Magnussona Saga's Visions of the World and Home
Authors: Norako Leila K.
Published: July 2014

Though the crusades have garnered significant critical interest of late, little attention has been paid to the effects of the crusades on the literature of medieval Scandinavia. This article seeks to shed light on this understudied area by exploring the representation of crusading in the Old Icelandic Magnussona Saga, a narrative that tells the story of Sigurðr I of Norway and his crusade to the Holy Land in the early 12th century. Exploring the saga's global vision – and how it differs from that seen in other European texts – allows for a fuller understanding of the representations of the crusades during the global Middle Ages, particularly in terms of how these campaigns affected European literatures, even those produced on the fringes of the known world.
Magnitude and determinants of malnutrition among pregnant women in eastern Ethiopia: evidence from rural, community‐based setting
Authors: Kedir Haji , Berhane Yemane , Worku Alemayehu
Published: July 2014

Maternal malnutrition is a worldwide public health problem affecting a high proportion of pregnant women. This study aimed to determine the magnitude and determinants of malnutrition among pregnant women in eastern Ethiopia. A cross‐sectional study was conducted on 1731 pregnant women selected by a cluster random sampling method. Data on maternal anthropometry and other factors were gathered by trained data collectors. Mid‐upper arm circumference < 22 cm defined malnutrition. Mixed‐effect, multilevel logistic regression was used to control clustering effect. On average, 19.06% of subjects were malnourished, while 23.3% study participants were underweight (body mass index < 19.8 kg m−2). In the final adjusted analysis, the risk of malnutrition was more than twofold higher in pregnant women with low (adjusted odds ratio = 2.47, 95% confidence interval = 1.41–4.34) and medium (adjusted odds ratio = 2.74, 95% confidence interval = 1.40–5.35) autonomy of household decision‐making than those who had high level of autonomy in household decision‐making. Husband illiteracy and not owning livestock were associated with increased risk of malnutrition. Women in the second and third trimester had a 66% and nearly twofold increased risk of malnutrition compared with their counterparts in the first trimester, respectively. Women who improved their eating habits had a 53% lower risk of malnutrition than those who did not. The risk of malnutrition was 39% lower in respondents who received prenatal dietary advice than in those who did not. Malnutrition affects at least one of every five pregnant women studied, calling for priority attention. Interventions that improve maternal involvement in household decision‐making autonomy and provision of prenatal dietary advice are recommended.
Vahid,Burge, and Perceptual Entitlement
Authors: Altschul Jon , Brueckner Anthony , Buford Christopher
Published: July 2014

HamidVahid criticizesTylerBurge's account of perceptual entitlement.Vahid argues thatBurge's account fails to satisfy a criterion of adequacy that any correct account of perceptual warrant must satisfy. According toVahid, a correct account of perceptual warrant must allow for perceptual beliefs which are produced by a properly functioning perceptual system yet which lack warrant. The present article argues thatVahid's critique ofBurge fails. It presents numerous examples of such beliefs that are consistent with Burge's account of perceptual entitlement.
Whole Lives and Good Deaths
Authors: Behrendt Kathy
Published: July 2014

This article discusses two views associated with narrative conceptions of the self. The first view asserts that our whole life is reasonably regarded as a single unit of meaning. A prominent strand of the philosophical narrative account of the self is the representative of this view. The second view—which has currency beyond the confines of the philosophical narrative account—is that the meaning of a life story is dependent on what happens at the end of it. The article argues that the connection between these two views is more tentative than often supposed: philosophical narrativists that see life as a single unit of value and meaning nonetheless provide grounds for arguing that the end of life is not the best and may be a particularly bad time to approach and intervene in the matter of how well one's life as a whole has gone.
Biofilm formation by Bacillus subtilis: new insights into regulatory strategies and assembly mechanisms
Authors: Cairns Lynne S. , Hobley Laura , Stanley‐Wall Nicola R.
Published: July 2014

Biofilm formation is a social behaviour that generates favourable conditions for sustained survival in the natural environment. For the Gram‐positive bacterium Bacillus subtilis the process involves the differentiation of cell fate within an isogenic population and the production of communal goods that form the biofilm matrix. Here we review recent progress in understanding the regulatory pathways that control biofilm formation and highlight developments in understanding the composition, function and structure of the biofilm matrix.
A framework to gauge the epidemic potential of plant pathogens in environmental reservoirs: the example of kiwifruit canker
Authors: Bartoli Claudia , Lamichhane Jay Ram , Berge Odile , Guilbaud Caroline , Varvaro Leonardo , Balestra Giorgio M. , Vinatzer Boris A. , Morris Cindy E.
Published: July 2014

New economically important diseases on crops and forest trees emerge recurrently. An understanding of where new pathogenic lines come from and how they evolve is fundamental for the deployment of accurate surveillance methods. We used kiwifruit bacterial canker as a model to assess the importance of potential reservoirs of new pathogenic lineages. The current kiwifruit canker epidemic is at least the fourth outbreak of the disease on kiwifruit caused byPseudomonas syringaein the mere 50 years in which this crop has been cultivated worldwide, with each outbreak being caused by different genetic lines of the bacterium. Here, we ask whether strains in natural (non‐agricultural) environments could cause future epidemics of canker on kiwifruit. To answer this question, we evaluated the pathogenicity, endophytic colonization capacity and competitiveness on kiwifruit ofP. syringaestrains genetically similar to epidemic strains and originally isolated from aquatic and subalpine habitats. All environmental strains possessing an operon involved in the degradation of aromatic compounds via the catechol pathway grew endophytically and caused symptoms in kiwifruit vascular tissue. Environmental and epidemic strains showed a wide host range, revealing their potential as future pathogens of a variety of hosts. Environmental strains co‐existed endophytically withCFBP7286, an epidemic strain, and shared about 20 virulence genes, but were missing six virulence genes found in all epidemic strains. By identifying the specific gene content in genetic backgrounds similar to known epidemic strains, we developed criteria to assess the epidemic potential and to survey for such strains as a means of forecasting and managing disease emergence.
Derivative of plant phenolic compound inhibits the type III secretion system of Dickeya dadantii via HrpX/HrpY two‐component signal transduction and Rsm systems
Authors: Li Yan , Hutchins William , Wu Xiaogang , Liang Cuirong , Zhang Chengfang , Yuan Xiaochen , Khokhani Devanshi , Chen Xin , Che Yizhou , Wang Qi , Yang Ching‐Hong
Published: July 2014

The type III secretion system (T3SS) is a major virulence factor in many Gram‐negative bacterial pathogens and represents a particularly appealing target for antimicrobial agents. Previous studies have shown that the plant phenolic compound p‐coumaric acid (PCA) plays a role in the inhibition of T3SS expression of the phytopathogen Dickeya dadantii 3937. This study screened a series of derivatives of plant phenolic compounds and identified that trans‐4‐hydroxycinnamohydroxamic acid (TS103) has an eight‐fold higher inhibitory potency than PCA on the T3SS of D. dadantii. The effect of TS103 on regulatory components of the T3SS was further elucidated. Our results suggest that TS103 inhibits HrpY phosphorylation and leads to reduced levels of hrpS and hrpL transcripts. In addition, through a reduction in the RNA levels of the regulatory small RNA RsmB, TS103 also inhibits hrpL at the post‐transcriptional level via the rsmB‐RsmA regulatory pathway. Finally, TS103 inhibits hrpL transcription and mRNA stability, which leads to reduced expression of HrpL regulon genes, such as hrpA and hrpN. To our knowledge, this is the first inhibitor to affect the T3SS through both the transcriptional and post‐transcriptional pathways in the soft‐rot phytopathogen D. dadantii 3937.
Methotrexate myelopathy with extensive transverse necrosis: Report of an autopsy case
Authors: Shintaku Masayuki , Toyooka Nao , Koyama Takashi , Teraoka Shunsuke , Tsudo Mitsuru
Published: July 2014

The patient was a 70‐year‐old woman with lymphoplasmacytic lymphoma which showed a predominantly diffuse involvement of the bone marrow and kidney. Because atypical lymphocytes appeared in the cerebrospinal fluid, the intrathecal administration of methotrexate (MTX) and cytosine arabinoside (Ara‐C) was repeated several times. The patient developed flaccid paraplegia 8 months after the beginning of intrathecal administration, and died 4 months later. Autopsy demonstrated extensive transverse necrosis involving the lower thoracic cord and marked vacuolar degeneration of the white matter of the cervical, upper thoracic and lumbo‐sacral cord. Focal vacuolar degeneration of the white matter was also noted in the left parietal lobe. Although vacuolar degeneration of the white matter is a common feature in MTX myelopathy, extensive transverse necrosis is rare. In the present case, an overlapping of two mechanisms, that is, injury of vascular endothelial cells and the direct toxic effect of MTX and Ara‐C on the white matter, probably played a crucial role in the pathogenesis of severe myelopathy. Because severe myelopathy occurs infrequently, considering the large number of patients receiving the intrathecal administration of MTX, it is possible that a constitutional predisposition or abnormal sensitivity to MTX was involved in the pathogenesis in the present patient.
Spatial and temporal variation in plant hydraulic traits and their relevance for climate change impacts on vegetation
Authors: Anderegg William R. L.
Published: July 2014

Plant hydraulics mediate terrestrial woody plant productivity, influencing global water, carbon, and biogeochemical cycles, as well as ecosystem vulnerability to drought and climate change. While inter‐specific differences in hydraulic traits are widely documented, intra‐specific hydraulic variability is less well known and is important for predicting climate change impacts. Here, I present a conceptual framework for this intra‐specific hydraulic trait variability, reviewing the mechanisms that drive variability and the consequences for vegetation response to climate change. I performed a meta‐analysis on published studies (n = 33) of intra‐specific variation in a prominent hydraulic trait – water potential at which 50% stem conductivity is lost (P50) – and compared this variation to inter‐specific variability within genera and plant functional types used by a dynamic global vegetation model. I found that intra‐specific variability is of ecologically relevant magnitudes, equivalent to c. 33% of the inter‐specific variability within a genus, and is larger in angiosperms than gymnosperms, although the limited number of studies highlights that more research is greatly needed. Furthermore, plant functional types were poorly situated to capture key differences in hydraulic traits across species, indicating a need to approach prediction of drought impacts from a trait‐based, rather than functional type‐based perspective.
A new look at water transport regulation in plants
Authors: Martínez‐Vilalta Jordi , Poyatos Rafael , Aguadé David , Retana Javier , Mencuccini Maurizio
Published: July 2014

Plant function requires effective mechanisms to regulate water transport at a variety of scales. Here, we develop a new theoretical framework describing plant responses to drying soil, based on the relationship between midday and predawn leaf water potentials. The intercept of the relationship (Λ) characterizes the maximum transpiration rate per unit of hydraulic transport capacity, whereas the slope (σ) measures the relative sensitivity of the transpiration rate and plant hydraulic conductance to declining water availability.

This framework was applied to a newly compiled global database of leaf water potentials to estimate the values of Λ and σ for 102 plant species.

Our results show that our characterization of drought responses is largely consistent within species, and that the parameters Λ and σ show meaningful associations with climate across species. Parameter σ was ≤1 in most species, indicating a tight coordination between the gas and liquid phases of water transport, in which canopy transpiration tended to decline faster than hydraulic conductance during drought, thus reducing the pressure drop through the plant.

The quantitative framework presented here offers a new way of characterizing water transport regulation in plants that can be used to assess their vulnerability to drought under current and future climatic conditions.
The monolignol pathway contributes to the biosynthesis of volatile phenylpropenes in flowers
Authors: Muhlemann Joëlle K. , Woodworth Benjamin D. , Morgan John A. , Dudareva Natalia
Published: July 2014

Volatile phenylpropenes play important roles in the mediation of interactions between plants and their biotic environments. Their biosynthesis involves the elimination of the oxygen functionality at the side‐chain of monolignols and competes with lignin formation for monolignol utilization. We hypothesized that biochemical steps before the monolignol branch point are shared between phenylpropene and lignin biosynthesis; however, genetic evidence for this shared pathway has been missing until now.

Our hypothesis was tested by RNAi suppression of the petunia (Petunia hybrida) cinnamoyl‐CoA reductase 1 (PhCCR1), which catalyzes the first committed step in monolignol biosynthesis. Detailed metabolic profiling and isotopic labeling experiments were performed in petunia transgenic lines.

Downregulation of PhCCR1 resulted in reduced amounts of total lignin and decreased flux towards phenylpropenes, whereas internal and emitted pools of phenylpropenes remained unaffected. Surprisingly, PhCCR1 silencing increased fluxes through the general phenylpropanoid pathway by upregulating the expression of cinnamate‐4‐hydroxylase (C4H), which catalyzes the second reaction in the phenylpropanoid pathway.

In conclusion, our results show that PhCCR1 is involved in both the biosynthesis of phenylpropenes and lignin production. However, PhCCR1 does not perform a rate‐limiting step in the biosynthesis of phenylpropenes, suggesting that scent biosynthesis is prioritized over lignin formation in petals.
Forecasting GDP over the Business Cycle in a Multi‐Frequency and Data‐Rich Environment
Authors: Bessec Marie , Bouabdallah Othman
Published: July 2014

This paper merges two specifications recently developed in the forecasting literature: the MS‐MIDAS model (Guérin and Marcellino, 2013) and the factor‐MIDAS model (Marcellino and Schumacher, 2010). The MS‐factor MIDAS model that we introduce incorporates the information provided by a large data set consisting of mixed frequency variables and captures regime‐switching behaviours. Monte Carlo simulations show that this specification tracks the dynamics of the process and predicts the regime switches successfully, both in‐sample and out‐of‐sample. We apply this model to US data from 1959 to 2010 and properly detect recessions by exploiting the link between GDP growth and higher frequency financial variables.
Does Co‐authorship Lead to Higher Academic Productivity?
Authors: Ductor Lorenzo
Published: July 2014

In recent decades, co‐authorship and policies aimed at inducing academic collaboration have increased simultaneously. Assuming that intellectual collaboration is exogenously determined, prior studies found a negative relationship between co‐authorship and productivity. I examine a panel data on economists publishing from 1970 to 2011 to test the causal effect of intellectual collaboration on intellectual output. As characteristics of the individual and her opportunity set are endogenously related to both collaboration and productivity, I instrument the amount of co‐authorship by the common research interest between an author and her potential co‐authors. After controlling for endogenous co‐authorship formation, unobservable heterogeneity and time varying factors, the effect of intellectual collaboration on individual performance becomes positive.
Increase of fast nutrient cycling in grassland microcosms through insect herbivory depends on plant functional composition and species diversity
Authors: Nitschke Norma , Wiesner Kerstin , Hilke Ines , Eisenhauer Nico , Oelmann Yvonne , Weisser Wolfgang W.
Published: July 2014

Nutrient cycling in terrestrial ecosystems is affected by various factors such as plant diversity and insect herbivory. While several studies suggest insect herbivory to depend on plant diversity, their interacting effect on nutrient cycling is unclear.

In a greenhouse experiment with grassland microcosms of one to six plant species of two functional groups (grasses and legumes), we tested the influence of plant species richness (diversity) and functional composition on plant community biomass production, insect foliar herbivory, soil microbial biomass, and nutrient concentrations in throughfall. To manipulate herbivory, zero, three or six generalist grasshoppers (Chorthippus parallelus) were added to the plant communities.

Increasing plant species richness increased shoot biomass and grasshopper performance, without significantly affecting root biomass or insect herbivory. Plant functional composition affected all of these parameters, e.g. legume communities showed the highest shoot biomass, the lowest grasshopper performance and suffered the least herbivory. Nutrient concentrations (dissolved mineral N, PO4‐P, SO4‐S) and pH in throughfall increased with herbivory. PO4‐P and pH increases were positively affected by plant diversity, especially under high herbivore pressure. Plant functional composition affected several throughfall variables, sometimes fully explaining diversity effects. Increasing plant diversity tended to increase soil microbial biomass, but only under high herbivore pressure. Faeces quantities strongly correlated with changes in pH and PO4‐P; frass may therefore be an important driver of throughfall pH and a main source of PO4‐P released from living plants. Our results indicate that insect herbivory may significantly influence fast nutrient cycling processes in natural communities, particularly so in managed grasslands.
Efficient transformation and artificial miRNA gene silencing in Lemna minor
Authors: Cantó‐Pastor A. , Mollá‐Morales A. , Ernst E. , Dahl W. , Zhai J. , Yan Y. , Meyers B. C. , Shanklin J. , Martienssen R.
Published: July 2014

Despite rapid doubling time, simple architecture and ease of metabolic labelling, a lack of genetic tools in the Lemnaceae (duckweed) has impeded the full implementation of this organism as a model for biological research. Here, we present technologies to facilitate high‐throughput genetic studies in duckweed. We developed a fast and efficient method for producing Lemna minor stable transgenic fronds via Agrobacterium‐mediated transformation and regeneration from tissue culture. Additionally, we engineered an artificial microRNA (amiRNA) gene silencing system. We identified a Lemna gibba endogenous miR166 precursor and used it as a backbone to produce amiRNAs. As a proof of concept we induced the silencing of CH42, a magnesium chelatase subunit, using our amiRNA platform. Expression of CH42 in transgenic L. minor fronds was significantly reduced, which resulted in reduction of chlorophyll pigmentation. The techniques presented here will enable tackling future challenges in the biology and biotechnology of Lemnaceae.
A novel Dual Probe Complex Trial Protocol for detection of concealed information
Authors: Labkovsky Elena , Rosenfeld J. Peter
Published: July 2014

In simply guilty (SG), countermeasure‐using guilty (CM), and innocent (IN) subjects, a new concealed information test, the P300‐based Dual Probe Complex Trial Protocol was tested in a mock crime scenario. It combines an oddball protocol with two stimuli (probe, irrelevant) and another with three stimuli (probe, irrelevant, target) into one trial, doubling detected mock crime information per unit time, compared to previous protocols. Probe‐irrelevant amplitude differences were significant in SG and CM, but not IN subjects. On a measure from both two and three stimulus protocol parts of the Dual Probe Complex Trial Protocol trial, accuracy was 94.7% (based on a .9 bootstrap criterion). The criterion‐independent area (AUC) under the receiver operating characteristic (from signal detection theory) measuring SG and CM versus IN discriminability averaged .92 (in a range of 0.5–1.0). Countermeasures enhanced irrelevant (not probe) P300s in CM groups.
Concerns, Challenges, and Directions of Development for the Issue of Representing Uncertainty in Risk Assessment
Authors: Flage Roger , Aven Terje , Zio Enrico , Baraldi Piero
Published: July 2014

In the analysis of the risk associated to rare events that may lead to catastrophic consequences with large uncertainty, it is questionable that the knowledge and information available for the analysis can be reflected properly by probabilities. Approaches other than purely probabilistic have been suggested, for example, using interval probabilities, possibilistic measures, or qualitative methods. In this article, we look into the problem and identify a number of issues that are foundational for its treatment. The foundational issues addressed reflect on the position that “probability is perfect” and take into open consideration the need for an extended framework for risk assessment that reflects the separation that practically exists between analyst and decisionmaker.
Hysteresis in Potential Output and Monetary Policy
Authors: Kienzler Daniel , Schmid Kai D.
Published: July 2014

We show that actively stabilizing economic activity plays a more prominent role in the conduct of monetary policy when potential output is subject to hysteresis. We augment a basic New Keynesian model by hysteresis in potential output and contrast simulation outcomes of this extended model to the standard model. We find that considering hysteresis allows for a more realistic amplification of macroeconomic shocks and persistent movements in output after monetary shocks. Our central policy implication of active output gap stabilization arises from stability analyses and welfare considerations.
Should They Stay or Should They Go? Attitudes Towards Immigration in Europe
Authors: Bridges Sarah , Mateut Simona
Published: July 2014

This paper examines the main determinants of individual attitudes towards immigration inEurope. Our results suggest that both economic and non‐economic variables shape attitudes towards immigration, but the relative importance of these factors depends crucially on the race/ethnicity of the arriving immigrants. While fears over labour market competition are more likely to shape attitudes towards the arrival of same race immigrants, more exposure to immigrants reduces opposition towards the arrival of different race immigrants. These findings persist after controlling for socioeconomic characteristics, and after exploiting the data to allow for cohort‐specific effects.
The Dynamics of Aid and Political Rights
Authors: Fielding David
Published: July 2014

Using cross‐country panel data, we explore the extent to which the variation over time in measures of democracy and political rights can be explained by changes in aid inflows, thus providing direct evidence on the impact of innovations in donor policy on the quality of recipient governance. We distinguish between the short‐run and long‐run effects of changes in aid. Our results are very different from those based on cross‐country variation in aid inflows. We find evidence of large differences between the effect of aid for political reform and the effect of other types of aid in aggregate. These effects also depend on the recipient country's initial level of political development. There is no evidence that aid intended for political reform has achieved its objective, and in some countries, it may be counterproductive. However, aggregate aid can have a beneficial effect on political rights.
Erythrocytes from GGTA1/CMAH knockout pigs: implications for xenotransfusion and testing in non‐human primates
Authors: Wang Zheng‐Yu , Burlak Christopher , Estrada Jose L. , Li Ping , Tector Matthew F. , Tector A. Joseph
Published: July 2014

Background

Pig erythrocytes are potentially useful to solve the worldwide shortage of human blood for transfusion. Domestic pig erythrocytes, however, express antigens that are bound by human preformed antibodies. Advances in genetic engineering have made it possible to rapidly knock out the genes of multiple xenoantigens, namely galactose α1,3 galactose (aGal) and N‐glycolylneuraminic acid (Neu5Gc). We have recently targeted the GGTA1 and CMAH genes with zinc finger endonucleases resulting in double knockout pigs that no longer express aGal or Neu5Gc and attract significantly fewer human antibodies. In this study, we characterized erythrocytes from domestic and genetically modified pigs, baboons, chimpanzees, and humans for binding of human and baboon natural antibody, and complement‐mediated lysis.

Methods

Distribution of anti‐Neu5Gc IgG and IgM in pooled human AB serum was analyzed by ELISA. Erythrocytes from domestic pigs (Dom), aGal knockout pigs (GGTA1 KO), aGal and Neu5Gc double knockout pigs (GGTA1/CMAH KO), baboons, chimpanzees, and humans were analyzed by flow cytometry for aGal and Neu5Gc expression. In vitro comparative analysis of erythrocytes was conducted with pooled human AB serum and baboon serum. Total antibody binding was accessed by hemagglutination; complement‐dependent lysis was measured by hemolytic assay; IgG or IgM binding to erythrocytes was characterized by flow cytometry.

Results

The pooled human AB serum contained 0.38 μg/ml anti‐Neu5Gc IgG and 0.085 μg/ml anti‐Neu5Gc IgM. Both Gal and Neu5Gc were not detectable on GGTA1/CMAH KO erythrocytes. Hemagglutination of GGTA1/CMAH KO erythrocytes with human serum was 3.5‐fold lower compared with GGTA1 KO erythrocytes, but 1.6‐fold greater when agglutinated with baboon serum. Hemolysis of GGTA1/CMAH KO erythrocytes by human serum (25%) was reduced 9‐fold compared with GGTA1 KO erythrocytes, but increased 1.64‐fold by baboon serum. Human IgG binding was reduced 27‐fold on GGTA1/CMAH KO erythrocytes compared with GGTA1 KO erythrocytes, but markedly increased 3‐fold by baboon serum IgG. Human IgM binding was decreased 227‐fold on GGTA1/CMAH KO erythrocytes compared with GGTA1 KO erythrocytes, but enhanced 5‐fold by baboon serum IgM.

Conclusions

Removal of aGal and Neu5Gc antigens from pig erythrocytes significantly reduced human preformed antibody‐mediated cytotoxicity but may have complicated future in vivo analysis by enhancing reactivity from baboons. The creation of the GGTA1/CMAH KO pig has provided the xenotransplantation researcher with organs and cells that attract fewer human antibodies than baboon and our closest primate relative, chimpanzee. These finding suggest that while GGTA1/CMAH KO erythrocytes may be useful for human transfusions, in vivo testing in the baboon may not provide a direct transplantation to the clinic.
Stiffness Analysis and Control of a Stewart Platform-Based Manipulator With Decoupled Sensor–Actuator Locations for Ultrahigh Accuracy Positioning Under Large External Loads
Authors: Ding Boyin , Cazzolato Benjamin S. , Stanley Richard M. , Grainger Steven , Costi John J.
Published: July 2014

Robot frame compliance has a large negative effect on the global accuracy of the system when large external forces/torques are exerted. This phenomenon is particularly problematic in applications where the robot is required to achieve ultrahigh (micron level) accuracy under very large external loads, e.g., in biomechanical testing and high precision machining. To ensure the positioning accuracy of the robot in these applications, the authors proposed a novel Stewart platform-based manipulator with decoupled sensor–actuator locations. The unique mechanism has the sensor locations fully decoupled from the actuator locations for the purpose of passively compensating for the load frame compliance, as a result improving the effective stiffness of the manipulator in six degrees of freedom (6DOF). In this paper, the stiffness of the proposed manipulator is quantified via a simplified method, which combines both an analytical model (robot kinematics error model) and a numerical model [finite element analysis (FEA) model] in the analysis. This method can be used to design systems with specific stiffness requirements. In the control aspect, the noncollocated positions of the sensors and actuators lead to a suboptimal control structure, which is addressed in the paper using a simple Jacobian-based decoupling method under both kinematics- and dynamics-based control. Simulation results demonstrate that the proposed manipulator configuration has an effective stiffness that is increased by a factor of greater than 15 compared to a general design. Experimental results show that the Jacobian-based decoupling method effectively increases the dynamic tracking performance of the manipulator by 25% on average over a conventional method.
Tracking Control of Limit Cycle Oscillations in an Aero-Elastic System
Authors: Bialy B. J. , Pasiliao Crystal L. , Dinh H. T. , Dixon W. E.
Published: July 2014

Limit cycle oscillations (LCOs) affect current fighter aircraft and are expected to be present on next generation fighter aircraft. Current efforts in control systems designed to suppress LCO behavior have either used a linear model, restricting the flight regime, require exact knowledge of the system dynamics, or require uncertainties in the system dynamics to be linear-in-the-parameters and only present in the torsional stiffness. Furthermore, the aerodynamic model used in prior research efforts neglects nonlinear effects. This paper presents the development of a controller consisting of a continuous robust integral of the sign of the error (RISE) feedback term with a neural network (NN) feedforward term to achieve asymptotic tracking of uncertainties that do not satisfy the linear-in-the-parameters assumption. Simulation results are presented to validate the performance of the developed controller.
Targeting membrane-expressed IgE B cell receptor with an antibody to the M1 prime epitope reduces IgE production
Authors: Gauvreau Gail M. , Harris Jeffrey M. , Boulet Louis-Philippe , Scheerens Heleen , Fitzgerald J. Mark , Putnam Wendy S. , Cockcroft Donald W. , Davis Beth E. , Leigh Richard , Zheng Yanan , Dahlén Barbro , Wang Yehong , Maciuca Romeo , Mayers Irvin , Liao X. Charlene , Wu Lawren C. , Matthews John G. , O’Byrne Paul M.
Published: July 2014

A humanized monoclonal antibody that targets the membrane IgE B cell receptor was associated with improvements in asthmatic airway responses.
Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor
Authors: Pegu Amarendra , Yang Zhi-yong , Boyington Jeffrey C. , Wu Lan , Ko Sung-Youl , Schmidt Stephen D. , McKee Krisha , Kong Wing-Pui , Shi Wei , Chen Xuejun , Todd John-Paul , Letvin Norman L. , Huang Jinghe , Nason Martha C. , Hoxie James A. , Kwong Peter D. , Connors Mark , Rao Srinivas S. , Mascola John R. , Nabel Gary J.
Published: July 2014

Neutralizing antibodies to HIV-1 envelope protect more effectively than an antibody to the CD4 cell receptor in rhesus macaques.
“C”ing Bacterial Infections
Authors: Nishijima Daniel K.
Published: July 2014

The diagnostic accuracy of the C-reactive protein test for identifying bacterial infections in febrile children was improved by including the time of fever onset.
Campylobacter jejuni Is Not Merely a Commensal in Commercial Broiler Chickens and Affects Bird Welfare
Authors: Humphrey Suzanne , Chaloner Gemma , Kemmett Kirsty , Davidson Nicola , Williams Nicola , Kipar Anja , Humphrey Tom , Wigley Paul
Published: July 2014

Campylobacter jejuni
is the leading cause of bacterial food-borne infection; chicken meat is its main source.
C. jejuni
is considered commensal in chickens based on experimental models unrepresentative of commercial production. Here we show that the paradigm of
Campylobacter
commensalism in the chicken is flawed. Through experimental infection of four commercial breeds of broiler chickens, we show that breed has a significant effect on
C. jejuni
infection and the immune response of the animals, although these factors have limited impact on the number of bacteria in chicken ceca. All breeds mounted an innate immune response. In some breeds, this response declined when interleukin-10 was expressed, consistent with regulation of the intestinal inflammatory response, and these birds remained healthy. In another breed, there was a prolonged inflammatory response, evidence of damage to gut mucosa, and diarrhea. We show that bird type has a major impact on infection biology of
C. jejuni
. In some breeds, infection leads to disease, and the bacterium cannot be considered a harmless commensal. These findings have implications for the welfare of chickens in commercial production where
C. jejuni
infection is a persistent problem.

IMPORTANCE
Campylobacter jejuni
is the most common cause of food-borne bacterial diarrheal disease in the developed world. Chicken is the most common source of infection.
C. jejuni
infection of chickens had previously not been considered to cause disease, and it was thought that
C. jejuni
was part of the normal microbiota of birds. In this work, we show that modern rapidly growing chicken breeds used in intensive production systems have a strong inflammatory response to
C. jejuni
infection that can lead to diarrhea, which, in turn, leads to damage to the feet and legs on the birds due to standing on wet litter. The response and level of disease varied between breeds and is related to regulation of the inflammatory immune response. These findings challenge the paradigm that
C. jejuni
is a harmless commensal of chickens and that
C. jejuni
infection may have substantial impact on animal health and welfare in intensive poultry production
.
Engineered Endolysin-Based “Artilysins” To Combat Multidrug-Resistant Gram-Negative Pathogens
Authors: Briers Yves , Walmagh Maarten , Van Puyenbroeck Victor , Cornelissen Anneleen , Cenens William , Aertsen Abram , Oliveira Hugo , Azeredo Joana , Verween Gunther , Pirnay Jean-Paul , Miller Stefan , Volckaert Guido , Lavigne Rob
Published: July 2014

The global threat to public health posed by emerging multidrug-resistant bacteria in the past few years necessitates the development of novel approaches to combat bacterial infections. Endolysins encoded by bacterial viruses (or phages) represent one promising avenue of investigation. These enzyme-based antibacterials efficiently kill Gram-positive bacteria upon contact by specific cell wall hydrolysis. However, a major hurdle in their exploitation as antibacterials against Gram-negative pathogens is the impermeable lipopolysaccharide layer surrounding their cell wall. Therefore, we developed and optimized an approach to engineer these enzymes as outer membrane-penetrating endolysins (Artilysins), rendering them highly bactericidal against Gram-negative pathogens, including
Pseudomonas aeruginosa
and
Acinetobacter baumannii
. Artilysins combining a polycationic nonapeptide and a modular endolysin are able to kill these (multidrug-resistant) strains
in vitro
with a 4 to 5 log reduction within 30 min. We show that the activity of Artilysins can be further enhanced by the presence of a linker of increasing length between the peptide and endolysin or by a combination of both polycationic and hydrophobic/amphipathic peptides. Time-lapse microscopy confirmed the mode of action of polycationic Artilysins, showing that they pass the outer membrane to degrade the peptidoglycan with subsequent cell lysis. Artilysins are effective
in vitro
(human keratinocytes) and
in vivo
(
Caenorhabditis elegans
).

IMPORTANCE
Bacterial resistance to most commonly used antibiotics is a major challenge of the 21st century. Infections that cannot be treated by first-line antibiotics lead to increasing morbidity and mortality, while millions of dollars are spent each year by health care systems in trying to control antibiotic-resistant bacteria and to prevent cross-transmission of resistance. Endolysins—enzymes derived from bacterial viruses—represent a completely novel, promising class of antibacterials based on cell wall hydrolysis. Specifically, they are active against Gram-positive species, which lack a protective outer membrane and which have a low probability of resistance development. We modified endolysins by protein engineering to create Artilysins that are able to pass the outer membrane and become active against
Pseudomonas aeruginosa
and
Acinetobacter baumannii
, two of the most hazardous drug-resistant Gram-negative pathogens.
Interobserver variability in the assessment of aneurysm occlusion with the WEB aneurysm embolization system
Authors: Fiorella David , Arthur Adam , Byrne James , Pierot Laurent , Molyneux Andy , Duckwiler Gary , McCarthy Thomas , Strother Charles
Published: July 2014

Objective

The WEB (WEB aneurysm embolization system, Sequent Medical, Aliso Viejo, California, USA) is a self-expanding, nitinol, mesh device designed to achieve aneurysm occlusion after endosaccular deployment. The WEB Occlusion Scale (WOS) is a standardized angiographic assessment scale for reporting aneurysm occlusion achieved with intrasaccular mesh implants. This study was performed to assess the interobserver variability of the WOS.

Methods

Seven experienced neurovascular specialists were trained to apply the WOS. These physicians independently reviewed angiographic image sets from 30 patients treated with the WEB under blinded conditions. No additional clinical information was provided. Raters graded each image according to the WOS (complete occlusion, residual neck or residual aneurysm). Final statistics were calculated using the dichotomous outcomes of complete occlusion or incomplete occlusion. The interobserver agreement was measured by the generalized κ statistic.

Results

In this series of 30 test case aneurysms, observers rated 12–17 as completely occluded, 3–9 as nearly completely occluded, and 9–11 as demonstrating residual aneurysm filling. Agreement was perfect across all seven observers for the presence or absence of complete occlusion in 22 of 30 cases. Overall, interobserver agreement was substantial (κ statistic 0.779 with a 95% CI of 0.700 to 0.857).

Conclusions

The WOS allows a consistent means of reporting angiographic occlusion for aneurysms treated with the WEB device.
Minimally invasive cone beam CT-guided evacuation of parenchymal and ventricular hemorrhage using the Apollo system: proof of concept in a cadaver model
Authors: Fiorella David , Arthur Adam , Schafer Sebastian
Published: July 2014

Introduction

The Apollo system (Penumbra Inc, Alameda, California, USA) is a low profile irrigation–aspiration system designed for the evacuation of intracranial hemorrhage.

Objective

To demonstrate the feasibility of using Apollo in combination with cone beam CT guidance.

Methods

Parenchymal (n=1) and mixed parenchymal–intraventricular hematomas (n=1) were created in cadaver heads using a transvascular (n=1) or transcranial (n=1) approach. Hematomas were then imaged with cone beam CT (CB-CT), and the long axis of the hematoma defined. The CB-CT data were then used to guide transcranial access to the hematoma—defining the location of the burr hole and the path to the leading edge of the hematoma. An 8F vascular sheath was then placed under live fluoroscopic guidance into the hematoma. A second CB-CT was performed to confirm localization of the sheath. The hematoma was then demarcated on the CB-CT and the Apollo wand was introduced through the 8F sheath and irrigation–aspiration was performed under (periodic) live fluoroscopic guidance. The operators manipulated the wand within the visible boundaries of the hematoma. After irrigation–aspiration, a control CB-CT was performed to document reduction in hematoma volume.

Results

Transvascular and transcranial techniques were both successful in creating intracranial hematomas. Hematomas could be defined with conspicuity sufficient for localization and volumetric measurement using CB-CT. Live fluoroscopic guidance was effective in navigating a sheath into the leading aspect of a parenchymal hematoma and guiding irrigation–aspiration with the Apollo system. Irrigation–aspiration reduced the parenchymal hemorrhage volume from 14.8 to 1.7 cc in 189 s in the first case (parenchymal hemorrhage) and from 26.4 to 4.1 cc in 300 s in the second case (parenchymal and intraventricular hemorrhage).

Conclusions

The cadaver model described is a useful means of studying interventional techniques for intracranial hemorrhage. It seems feasible to use CB-CT to guide the evacuation of intraparenchymal and intraventricular hemorrhage using the Apollo system through a minimally invasive transcranial access.
Metabolomics of salivary fatigue markers in soccer players after consecutive games
Authors: Ra Song-Gyu , Maeda Seiji , Higashino Ryota , Imai Tomoko , Miyakawa Shumpei
Published: July 2014

Strenuous and consecutive exercise leads to fatigue symptoms in athletes. Metabolomics is a comprehensive method to assess metabolites that involves the measurements of the overall metabolic signature of biological samples. Using metabolomic analysis, we investigated the identification of salivary fatigue markers in soccer players after 3 consecutive days of a game program. One hundred twenty-two male soccer players participated in 3 consecutive days of a game program. To detect fatigued athletes, we measured indices of traditional fatigue symptoms, i.e., heart rate, body mass and mood, before and after the program. We detected 37 fatigued players throughout the program. Before and after the program, the saliva in these players was analyzed using capillary electrophoresis and time-of-flight mass spectrometry (CE-TOFMS) and a multivariate statistical technique, principal component analysis, was used to process the data. CE-TOFMS was used to identify 144 metabolites in the saliva of fatigued players. A significant metabolomic difference was observed before and after 3 consecutive days of a soccer game program. Interestingly, metabolites were all increased after the program (P < 0.001). The identified metabolites, including 3-methylhistidine, glucose 1- and 6-phosphate, taurine, and some amino acids, were involved in skeletal muscle catabolism, glucose metabolism, lipid metabolism, amino acid metabolism, and energy metabolism. Our work demonstrated some salivary metabolites were significantly increased in the fatigued players after consecutive days of short soccer matches. We propose that the detected salivary metabolites may be new fatigue markers in athletes.