bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitumor activities of agonistic anti-TNFR antibodies require differential FcγRIIB coengagement in vivo
Authors: Li Fubin , Ravetch Jeffrey V. 
Published: November 2013

Significance
Agonistic antibodies targeting key TNF receptor (TNFR) molecules involved in antitumor responses have been demonstrated as potent antitumor therapies in preclinical studies. However, no effective agonistic anti-TNFR therapies have been successfully developed to date. In contrast, cytotoxic antitumor antibodies targeting tumor antigens or antagonistic antibodies blocking key inhibitory checkpoints are widely used in clinical settings. One explanation for this discrepancy has been recently provided by the finding that agonistic anti-TNFR antibodies have a previously unappreciated requirement for inhibitory Fcγ receptor FcγRIIB coengagement. Understanding the differential FcγRIIB coengagement requirement by different antibodies and the in vivo cross-linking function of FcγRIIB, as defined by this study, not only has implications for the development of potent agonistic anti-TNFR therapies but also for the understanding of TNFR activation mechanisms.
DNAJC13 mutations in Parkinson disease
Authors: Vilariño-Güell Carles , Rajput Alex , Milnerwood Austen J. , Shah Brinda , Szu-Tu Chelsea , Trinh Joanne , Yu Irene , Encarnacion Mary , Munsie Lise N. , Tapia Lucia , Gustavsson Emil K. , Chou Patrick , Tatarnikov Igor , Evans Daniel M. , Pishotta Frederick T. , Volta Mattia , Beccano-Kelly Dayne , Thompson Christina , Lin Michelle K. , Sherman Holly E. , Han Heather J. , Guenther Bruce L. , Wasserman Wyeth W. , Bernard Virginie , Ross Colin J. , Appel-Cresswell Silke , Stoessl A. Jon , Robinson Christopher A. , Dickson Dennis W. , Ross Owen A. , Wszolek Zbigniew K. , Aasly Jan O. , Wu Ruey-Meei , Hentati Faycal , Gibson Rachel A. , McPherson Peter S. , Girard Martine , Rajput Michele , Rajput Ali H. , Farrer Matthew J. 
Published: November 2013

Abstract
A Saskatchewan multi-incident family was clinically characterized with Parkinson disease (PD) and Lewy body pathology. PD segregates as an autosomal-dominant trait, which could not be ascribed to any known mutation. DNA from three affected members was subjected to exome sequencing. Genome alignment, variant annotation and comparative analyses were used to identify shared coding mutations. Sanger sequencing was performed within the extended family and ethnically matched controls. Subsequent genotyping was performed in a multi-ethnic case–control series consisting of 2928 patients and 2676 control subjects from Canada, Norway, Taiwan, Tunisia, and the USA. A novel mutation in receptor-mediated endocytosis 8/RME-8 (DNAJC13 p.Asn855Ser) was found to segregate with disease. Screening of cases and controls identified four additional patients with the mutation, of which two had familial parkinsonism. All carriers shared an ancestral DNAJC13 p.Asn855Ser haplotype and claimed Dutch–German–Russian Mennonite heritage. DNAJC13 regulates the dynamics of clathrin coats on early endosomes. Cellular analysis shows that the mutation confers a toxic gain-of-function and impairs endosomal transport. DNAJC13 immunoreactivity was also noted within Lewy body inclusions. In late-onset disease which is most reminiscent of idiopathic PD subtle deficits in endosomal receptor-sorting/recycling are highlighted by the discovery of pathogenic mutations VPS35, LRRK2 and now DNAJC13. With this latest discovery, and from a neuronal perspective, a temporal and functional ecology is emerging that connects synaptic exo- and endocytosis, vesicular trafficking, endosomal recycling and the endo-lysosomal degradative pathway. Molecular deficits in these processes are genetically linked to the phenotypic spectrum of parkinsonism associated with Lewy body pathology.
Molecular and immunological characterization of β′-component (Onc k 5), a major IgE-binding protein in chum salmon roe
Authors: Shimizu Yutaka , Kishimura Hideki , Kanno Gaku , Nakamura Atsushi , Adachi Reiko , Akiyama Hiroshi , Watanabe Kazuhiko , Hara Akihiko , Ebisawa Motohiro , Saeki Hiroki 
Published: November 2013

Abstract
Salmon roe has a high allergic potency and often causes anaphylaxis in Japan. The major allergic protein of salmon roe is β′-component, which is a 35kDa vitellogenin fragment consisting of two subunits. To elucidate structural information and immunological characteristics, β′-component and the subunit components were purified from chum salmon (Onchorhincus keta) roe and vitellogenin-encoding mRNA was used to prepare β′-component subunit-encoding cDNA. This was PCR-amplified, cloned and sequenced and the deduced amino acid sequence compared with partial sequences of β′-component obtained by peptide mapping. The recombinant β′-component subunit was produced by bacterial expression in Escherichia coli and its IgE-binding ability was measured by ELISA using the sera of a patient allergic to salmon roe. This was then compared with that of the native β′-component with and without carboxymethylation. Following successful cloning of the cDNA encoding the β′-component subunit, 170 amino acid residues were deduced and matched with the amino acid sequences of 121 and 88 residues in the 16kDa and 18kDa subunits, respectively. The sequences of both β′-component subunits were almost identical, and the predicted secondary structure of the β′-component showed a high content of β-pleated sheets and no α-helices. There was no difference in IgE-binding ability between the native and recombinant β′-component subunits at the same protein concentration, regardless of carboxymethylation. In conclusion, β′-component is a homodimer protein composed of two isoform subunits having the same level of IgE-binding ability and, therefore, allergenic identity.
Meteor showers on Earth from sungrazing comets
Authors: Sekhar A. , Asher D. J. 
Published: November 2013

Abstract
Sungrazing comets have always captured a lot of interest and curiosity among the general public as well as scientists since ancient times. The perihelion passage of comet C/2012 S1 (ISON) at the end of this year (on 2013 November 28) is an eagerly awaited event. In this work, we do a mathematical study to check whether meteoroids ejected from this comet during its journey around the Sun can produce spectacular meteor phenomena on Earth. Our calculations show that although the orbital elements of this comet are much more favourable than for most sungrazers to have its descending node near the Earth's orbit, even ejection velocities as high as 1 km s−1 do not induce sufficient nodal dispersion to bring meteoroids to Earth intersection during present times. A similar result applies to Newton's comet C/1680 V1 which has surprisingly similar orbital elements, although it is known to be a distinct comet from C/2012 S1. Our analysis also shows that for meteoroids ejected from all known sungrazing groups during recent epochs, only the Marsden family (with required ejection velocities of some hundreds of m s−1) can produce meteor phenomena during present times. In a broader sense, we indicate why we do not observe visually brilliant meteor showers from frequently observed sungrazers.
Recovering Root System Traits Using Image Analysis Exemplified by Two-Dimensional Neutron Radiography Images of Lupine
Authors: Leitner Daniel , Felderer Bernd , Vontobel Peter , Schnepf Andrea 
Published: November 2013

Abstract
Root system traits are important in view of current challenges such as sustainable crop production with reduced fertilizer input or in resource-limited environments. We present a novel approach for recovering root architectural parameters based on image-analysis techniques. It is based on a graph representation of the segmented and skeletonized image of the root system, where individual roots are tracked in a fully automated way. Using a dynamic root architecture model for deciding whether a specific path in the graph is likely to represent a root helps to distinguish root overlaps from branches and favors the analysis of root development over a sequence of images. After the root tracking step, global traits such as topological characteristics as well as root architectural parameters are computed. Analysis of neutron radiographic root system images of lupine (Lupinus albus) grown in mesocosms filled with sandy soil results in a set of root architectural parameters. They are used to simulate the dynamic development of the root system and to compute the corresponding root length densities in the mesocosm. The graph representation of the root system provides global information about connectivity inside the graph. The underlying root growth model helps to determine which path inside the graph is most likely for a given root. This facilitates the systematic investigation of root architectural traits, in particular with respect to the parameterization of dynamic root architecture models.
Human herpesvirus‐6A gQ1 and gQ2 are critical for human CD46 usage
Authors: Jasirwan Chyntia , Furusawa Yoshikazu , Tang Huamin , Maeki Takahiro , Mori Yasuko 
Published: November 2013

ABSTRACTBased on genetic and antigenic differences and on their cell tropism, human herpes virus‐6 (HHV‐6) has been classified into two variants, HHV‐6A and HHV‐6B. Recently, these variants were re‐classified as two different species. The HHV‐6A glycoprotein complex, gH/gL/gQ1/gQ2 binds to its cellular receptor, CD46; however, the corresponding complex in HHV‐6B rarely binds to CD46. To determine which viral molecules in the glycoprotein complex determine HHV‐6A‐CD46 binding, each molecule of the HHV‐6A complex (i.e., gH, gL, gQ1, or gQ2) was replaced with the corresponding HHV‐6B molecule, and the ability of the replaced protein to be incorporated into the complex and the ability of the complex to bind CD46 were examined. It was found that when all four glycoproteins were expressed, they were able to form a tetrameric complex. However, a complex formed by HHV‐6A gH/gL/gQ1/gQ2 complexes replaced with HHV‐6B gQ1 or gQ2 scarcely bind CD46, whereas HHV‐6A complexes in which gH or gL was replaced with the HHV‐6B molecules did bind it. These results indicate that HHV‐6A gQ1 and gQ2 play an important role in CD46 binding.
Testing the roles of competition, facilitation and stochasticity on community structure in a species‐rich assemblage
Authors: Martorell Carlos , Freckleton Robert P. 
Published: November 2013

Summary

There is an ongoing debate about whether communities are closely integrated and bound together via interactions such as competition or facilitation, or are disintegrated and dominated by chance. We still lack community‐wide data on the intensities of interactions and randomness, and measurements of their impacts on community structure.

Using a long‐term data set, we sought to measure the effects of interactions and stochasticity in structuring a highly diverse (>100 species) semi‐arid grassland plant community, testing for positive and negative interactions at different stages of population growth of all species.

During the colonization of new patches, most species were facilitated or inhibited by several others. These opposite effects can potentially have a large effect on species abundances, but they were correlated and cancelled out at the community level. Nevertheless, competition during colonization was strong enough to cause poor competitors to have small population sizes.

The subsequent phase of population growth (increase and subsequent change in numbers within occupied patches) was mainly driven by intraspecific density dependence, and we found little evidence for interspecific interactions.

Model results showed that stochasticity and recurrent colonization of transient, favourable patches maintained diversity, keeping poor competitors from becoming extinct.

Synthesis: Our results, taken together with recent studies on tropical forests, suggest that weak interactions among established plants may be a general phenomenon, but that local interactions during colonization are important drivers of community composition. Most of the variance in species abundance in our community was explained by intraspecific competition and stochasticity, with interspecific interactions playing a minor role due to their overall weakness, interaction changes over ontogeny, and the cancellation of opposite‐sign interactions when all the species in the community are considered. Despite this, some species were rare seemingly because they cannot withstand interspecific competition. Thus, to untangle the effects of interactions on community structure, future research should focus on interactions occurring at different phases of population growth and on whole communities.
Risk Selection into Consumer‐Directed Health Plans: An Analysis of Family Choices within Large Employers
Authors: McDevitt Roland D. , Haviland Amelia M. , Lore Ryan , Laudenberger Laura , Eisenberg Matthew , Sood Neeraj 
Published: November 2013

ObjectiveTo identify the degree of selection into consumer‐directed health plans (CDHPs) versus traditional plans over time, and factors that influence choice and temper risk selection.Data Sources/Study SettingSixteen large employers offering both CDHP and traditional plans during the 2004–2007 period, more than 200,000 families.Study DesignWe model CDHP choice with logistic regression; predictors include risk scores, in addition to family, choice setting, and plan characteristics. Additional models stratify by account type or single enrollee versus family.Data Collection/Extraction MethodsRisk scores, family characteristics, and enrollment decisions are derived from medical claims and enrollment files. Interviews with human resources executives provide additional data.Principal FindingsCDHP risk scores were 74 percent of traditional plan scores in the first year, and this difference declined over time. Employer contributions to accounts and employee premium savings fostered CDHP enrollment and reduced risk selection. Having to make an active choice of plan increased CDHP enrollment but also increased risk selection. Risk selection was greater for singles than families and did not differ between HRA and HSA‐based CDHPs.ConclusionsRisk selection was not severe and it was well managed. Employers have effective methods to encourage CDHP enrollment and temper selection against traditional plans.
Computation of Standard Errors
Authors: Dowd Bryan E. , Greene William H. , Norton Edward C. 
Published: November 2013

ObjectivesWe discuss the problem of computing the standard errors of functions involving estimated parameters and provide the relevant computer code for three different computational approaches using two popular computer packages.Study DesignWe show how to compute the standard errors of several functions of interest: the predicted value of the dependent variable for a particular subject, and the effect of a change in an explanatory variable on the predicted value of the dependent variable for an individual subject and average effect for a sample of subjects.Empirical ApplicationUsing a publicly available dataset, we explain three different methods of computing standard errors: the delta method, Krinsky–Robb, and bootstrapping. We provide computer code for Stata 12 and LIMDEP 10/NLOGIT 5.ConclusionsIn most applications, choice of the computational method for standard errors of functions of estimated parameters is a matter of convenience. However, when computing standard errors of the sample average of functions that involve both estimated parameters and nonstochastic explanatory variables, it is important to consider the sources of variation in the function's values.
Reduction of Elevated Cytokine Levels in Acute/Acute‐on‐Chronic Liver Failure Using Super‐Large Pore Albumin Dialysis Treatment: An In Vitro Study
Authors: Dominik Adrian , Stange Jan , Pfensig Claudia , Borufka Luise , Weiss‐Reining Helga , Eggert Martin 
Published: November 2013

AbstractThe removal of small water soluble toxins and albumin‐bound toxins in acute liver failure patients (ALF) or acute‐on‐chronic liver failure (AocLF) patients has been established using extracorporeal liver support devices (e.g. Molecular Adsorbents Recirculating System; MARS). However, reduction of elevated cytokines in ALF/AocLF using MARS is still not efficient enough to lower patients' serum cytokine levels. New membranes with larger pores or higher cut‐offs should be considered in extracorporeal liver support devices based on albumin dialysis in order to address these problems, as the introduction of super‐large pore membranes could counterbalance high production rates of cytokines and further improve detoxification in vivo. Using an established in vitro two compartment albumin dialysis model, three novel membranes of different pore sizes were compared with the MARS Flux membrane for cytokine removal and detoxification qualities in vitro. Comparing the membranes, no improvement in the removal of water soluble toxins was found. Albumin‐bound toxins were removed more efficiently using novel large (Emic2) to super‐large pore sized membranes (S20; HCO Gambro). Clearance of cytokines IL‐6 and tumor necrosis factor‐α was drastically improved using super‐large pore membranes. The Emic2 membrane predominantly removed IL‐6. In vitro data suggest that the usage of larger pore sized membranes in albumin dialysis can efficiently reduce elevated cytokine levels and liver failure toxins. Using large to super‐large pore membranes might exert effects on patients' serum cytokine levels. Combined with increased detoxification this could lead to higher survival in ALF/AocLF. Promising membranes for clinical evaluation have been identified.
Keeping the Arctic ‘Cold’: The Rise of Plurilateral Diplomacy?
Authors: Bjola Corneliu 
Published: November 2013

AbstractAt a time when the Arctic region faces significant climatic transformations, a triple governance gap threatens to fuel major diplomatic tensions among regional actors over natural resources, navigation rights and fishery management. This article argues that a plurilateral diplomatic approach could help close these gaps by establishing an effective ‘web of contracts’ involving institutional networks defined around the Arctic Council as the central node of Arctic governance and NATO, the International Maritime Organization (IMO) and the United Nations Development Programme (UNDP) / the Global Environment Facility (GEF) as supporting agencies. In so doing, the article makes a twofold contribution to the literature on global governance. It explains how governance gaps could be closed in a manner that does not require extensive institutional frameworks or rigid legal mandates, and it highlights the role of institutional networks in sustaining regional and global governance.
Identity and War
Authors: Kaldor Mary 
Published: November 2013

AbstractThis article makes two arguments. First, sectarian identity (ethnic, tribal or religious) is an outcome of war rather than a cause of war, even though such identities make (selective) use of memory. The implication of this proposition is that war should be interpreted less as an external contest of will between two sides but rather as a one‐sided and/or parallel effort to construct unidimensional political identities as a basis for power. Power derived from identity so constructed is likely to be authoritarian and repressive. Second, different methods of communication provide the basis for different modalities of power and this matters; power diffuses through all forms of communication. But the language of violence is much less amenable to freedom and human emancipation than other nonviolent forms of communication. The arguments are elaborated through a critique of the work of the German legal theorist Carl Schmitt and his notion of the friend–enemy distinction as a basis of political authority. The article concludes by arguing that in a global era, when traditional inter‐state war is declining, there are greater possibilities for multiple identities and a layering of political authority, even though there are also efforts to resurrect the friend–enemy distinction in many ‘new wars’ and, above all, in the war on terror.
Does dominance of crossing retinal ganglion cells make the eyes cross? The temporal retina in the origin of infantile esotropia – a neuroanatomical and evolutionary analysis
Authors: ten Tusscher Marcel P. M. 
Published: November 2013

AbstractA closer look at the evolution of the eye and the brain provides a possible explanation for both the origin of infantile esotropia and its motor characteristics. In the course of evolution, the eyes have moved from a lateral to a frontal position. Consequently, the monocular visual fields started to overlap resulting in a binocular visual field. In lateral‐eyed animals, the retinae project to the contralateral visual cortices only. These projections are also found in binocular mammals and birds with binocular visual fields but in addition there are uncrossed projections from the temporal retinae to the visual cortex. The partial chiasmal decussation and the corpus callosum provide the necessary structure that allows binocular vision to develop. Disruption of normal binocular development causes a loss of binocularity in the primary visual cortex and beyond. Beyond the primary visual cortex, the contralateral eye dominates while the temporal retinal signal appears to lose influence. Loss or absence of binocular vision in infantile esotropia may be caused by inadequate retinotopic matching between the nasal and temporal retinal signals like in albinism with an abnormal or asymmetric chiasmal decussation or agenesis of the corpus callosum. Dominance of the crossing retinal signal might also explain the motor characteristics of infantile esotropia (asymmetric OKN, latent nystagmus, DVD). A normal binocular cortical signal will predominate over the evolutionary older, originally non‐binocular, retinal projections to the superior colliculi (CS) and the accessory optic system (AOS). A suppressed temporal retinal signal paves the way for the re‐emergence of eye movements driven by one eye, as in lateral‐eyed non‐binocular animals.
Differential satellite cell density of type I and II fibres with lifelong endurance running in old men
Authors: Mackey A. L. , Karlsen A. , Couppé C. , Mikkelsen U. R. , Nielsen R. H. , Magnusson S. P. , Kjaer M. 
Published: November 2013

AbstractAimTo investigate the influence of lifelong endurance running on the satellite cell pool of type I and type II fibres in healthy human skeletal muscle.MethodsMuscle biopsies were collected from 15 healthy old trained men (O‐Tr) who had been running 43 ± 16 (mean ± SD) kilometres a week for 28 ± 9 years. Twelve age‐matched untrained men (O‐Un) and a group of young trained and young untrained men were recruited for comparison. Frozen sections were immunohistochemically stained for Pax7, type I myosin and laminin, from which fibre area, the number of satellite cells, and the relationship between these variables were determined.ResultsIn O‐Un and O‐Tr, type II fibres were smaller and contained fewer satellite cells than type I fibres. However, when expressed relative to fibre area, the difference in satellite cell content between fibre types was eliminated in O‐Tr, but not O‐Un. A strong positive relationship between fibre size and satellite cell content was detected in trained individuals. In line with a history of myofibre repair, a greater number of fibres with centrally located myonuclei were detected in O‐Tr.ConclusionLifelong endurance training (i) does not deplete the satellite cell pool and (ii) is associated with a similar density of satellite cells in type I and II fibres despite a failure to preserve the equal fibre type distribution of satellite cells observed in young individuals. Taken together, these data reveal a differential regulation of satellite cell content between fibre types, in young and old healthy men with dramatically different training histories.