Redundant Contributions Research Articles

Contribution of Network Redundancy to Reducing Criticality of Road Links

Road networks are frequently disrupted by natural hazard events, producing severe consequences for isolated communities as well as increased travel times and significant reconstruction costs. Therefore, identifying which critical links need investment to reduce network impacts has become a priority for road agencies. Road network redundancy contributes to reducing these potential consequences by providing viable alternative routes. Although several metrics have been proposed in the literature to evaluate road criticality, including those based on topological variables and transportation cost increases, a comparison of the contribution of redundancy to reducing expected consequences has not been undertaken using a range of different metrics. This paper proposes a methodology to evaluate road criticality under different metrics and to quantify the contribution of redundancy in reducing expected impacts using the “full scan” method and Monte Carlo simulation. This methodology is then applied to a case study of New Zealand’s South Island to quantify the contribution of secondary and tertiary inter-urban roads to overall network redundancy, and to determine the most critical links under different approaches. The results obtained from the case study demonstrate that the redundancy level provided by secondary and tertiary inter-urban roads, over and above the state highway network, decreases expected transportation cost increases by 94.93% on average, and improves topological metrics, such as network betweenness values, by 73% on average when the road network is disrupted. The proposed methodology has the potential to help decision makers quantify and, therefore, prioritize investments to reduce the consequences of network disruptions.

Behavioural relevance of redundant and synergistic stimulus information between functionally connected neurons in mouse auditory cortex

Measures of functional connectivity have played a central role in advancing our understanding of how information is transmitted and processed within the brain. Traditionally, these studies have focused on identifying redundant functional connectivity, which involves determining when activity is similar across different sites or neurons. However, recent research has highlighted the importance of also identifying synergistic connectivity—that is, connectivity that gives rise to information not contained in either site or neuron alone. Here, we measured redundant and synergistic functional connectivity between neurons in the mouse primary auditory cortex during a sound discrimination task. Specifically, we measured directed functional connectivity between neurons simultaneously recorded with calcium imaging. We used Granger Causality as a functional connectivity measure. We then used Partial Information Decomposition to quantify the amount of redundant and synergistic information about the presented sound that is carried by functionally connected or functionally unconnected pairs of neurons. We found that functionally connected pairs present proportionally more redundant information and proportionally less synergistic information about sound than unconnected pairs, suggesting that their functional connectivity is primarily redundant. Further, synergy and redundancy coexisted both when mice made correct or incorrect perceptual discriminations. However, redundancy was much higher (both in absolute terms and in proportion to the total information available in neuron pairs) in correct behavioural choices compared to incorrect ones, whereas synergy was higher in absolute terms but lower in relative terms in correct than in incorrect behavioural choices. Moreover, the proportion of redundancy reliably predicted perceptual discriminations, with the proportion of synergy adding no extra predictive power. These results suggest a crucial contribution of redundancy to correct perceptual discriminations, possibly due to the advantage it offers for information propagation, and also suggest a role of synergy in enhancing information level during correct discriminations.

Global variation in unique and redundant mammal functional diversity across the daily cycle

AbstractAimOrganisms primarily influence ecosystems through their functional traits when they are physically active. Following the nocturnal bottleneck, the expansion of mammals into the daytime expanded mammalian functional diversity (FD), however there is also notable overlap in trait space across diel niches leading to redundant FD. We explore how the unique and redundant contribution of each diel niche varies spatially and in relation to natural variation in light and temperature.LocationGlobal.TaxonExtant mammals.MethodsBased on five major functional traits (body mass, litter size, diet breadth, foraging strata, habitat breadth) for 5033 extant terrestrial mammals, we determine biogeographical variation in nocturnal, crepuscular, cathemeral and diurnal FD. We calculate the proportion of mammalian FD that is unique to each diel niche, and the proportion that is redundant across the daily cycle.ResultsThe diversification of mammals into the daytime resulted in the creation of new FD (28.5% of FD is not nocturnal; Lower Quartile 17.3%; Upper Quartile 38.2%). Most of this expansion occurred at higher latitudes where uniquely cathemeral FD dominates (>55°N, 41.1% of mammalian FD; Lower Quartile 33.3%, Upper Quartile 53.6%), associated with fewer hours of biologically useful moonlight and daylight. Where there are more hours of biologically useful daylight, unique diurnal FD is common. However, more than half of non‐nocturnal FD is redundant, increasing ecosystem stability as different species carry out similar functions at different times of day, and suggesting that many mammals have not diversified far from their nocturnal ancestors.Main conclusionsOver much of the land surface more than a half of FD only occurs at night, underscoring the importance of nocturnal mammals for ecosystems. Understanding diel variation in FD not only informs on community structure and ecosystem function but also on ecosystem functional persistence in the Anthropocene, with pressures at night being particularly concerning.

A Novel Homozygous Stop Mutation in IL23R Causes Mendelian Susceptibility to Mycobacterial Disease

PurposeMendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-γ immunity. The most frequent genetic defects are found in IL12 or a subunit of its receptor. IL23R deficiency in MSMD has only been reported once, in two pediatric patients from the same kindred with isolated disseminated Bacille Calmette-Guérin disease. We evaluated the impact of a homozygous stop mutation in IL23R (R381X), identified by whole exome sequencing, in an adult patient with disseminated non-tuberculous mycobacterial disease.MethodsWe performed functional validation of the R381X mutation by evaluating IL23R expression and IL-23 signaling (STAT3 phosphorylation, IFN-γ production) in primary cells (PBMCs, EBV-B cells) and cell lines (HeLa) with or without back-complementation of wild-type IL23R.ResultsWe report on a 48-year-old male with disseminated non-tuberculous mycobacterial disease. We identified and characterized a homozygous loss-of-function stop mutation underlying IL23R deficiency, resulting in near absent expression of membrane bound IL23R. IL23R deficiency was characterized by impaired IL-23-mediated IFN-γ secretion in CD4+, CD8+ T, and mucosal-associated invariant T (MAIT) cells, and low frequencies of circulating Th17 (CD3+CD45RA−CCR4+CXCR3−RORγT+), Th1* (CD45RA−CCR4−CXCR3+RORγT+), and MAIT (CD3+CD8+Vα7.2+CD161+) cells. Although the patient did not have a history of recurrent fungal infections, impaired Th17 differentiation and blunted IL-23-mediated IL-17 secretion in PBMCs were observed.ConclusionWe demonstrate that impaired IL-23 immunity caused by a homozygous R381X mutation in IL23R underlies MSMD, corroborating earlier findings with a homozygous p.C115Y IL23R mutation. Our report further supports a model of redundant contribution of IL-23- to IL-17-mediated anti-fungal immunity.1

Directed mutational scanning reveals a balance between acidic and hydrophobic residues in strong human activation domains.

SUMMARYAcidic activation domains are intrinsically disordered regions of the transcription factors that bind coactivators. The intrinsic disorder and low evolutionary conservation of activation domains have made it difficult to identify the sequence features that control activity. To address this problem, we designed thousands of variants in seven acidic activation domains and measured their activities with a high-throughput assay in human cell culture. We found that strong activation domain activity requires a balance between the number of acidic residues and aromatic and leucine residues. These findings motivated a predictor of acidic activation domains that scans the human proteome for clusters of aromatic and leucine residues embedded in regions of high acidity. This predictor identifies known activation domains and accurately predicts previously unidentified ones. Our results support a flexible acidic exposure model of activation domains in which the acidic residues solubilize hydrophobic motifs so that they can interact with coactivators. A record of this paper’s transparent peer review process is included in the supplemental information.

Innovative Formulation in Discrete Kalman Filtering with Constraints - A Generic Framework for Comprehensive Error Analysis

This manuscript establishes a generic framework for comprehensive error analysis in discrete Kalman filtering with constraints, which systematically provides a complete set of algorithmic formulas along with demonstrating an alternative process of theoretical analytics of discrete Kalman filter. This constructive work aims extensively to standardize the formulation of Kalman filter with constraints. In analogy to the similar framework for standard discrete Kalman filter (without any constraints), the proposed framework specifically considers: model formulation vs. the error sources, the solution of the state and process noise vectors, the residuals for the process noise vector and the measurement noise vector, the redundancy contribution of the predicted state vector, process noise vector and measurement vector, and other relevant essential aspects, of which some of the features are essential to comprehensive error analysis, but are nonexistent yet in the primary algorithm in Kalman filtering with constraints. Besides, the algorithmic form of the Extended Kalman filter with constraints is also provided for practical purpose. At the end, specific remarks about the developed framework are given to emphasize on its usage to a certain extend.

The Symbol Digit Modalities Test (SDMT) is sensitive but non-specific in MS: Lexical access speed, memory, and information processing speed independently contribute to SDMT performance

BackgroundThe Symbol Digit Modalities Test (SDMT) is the most sensitive metric of neurocognitive function in multiple sclerosis (MS), and is consistently interpreted as a measure of information processing speed (IPS). ObjectiveTo evaluate the cognitive psychometric profile captured by the SDMT to identify whether different cognitive processes independently underlie performance. MethodsThree samples of MS patients (total n=661; 185 research patients at MS center; 370 clinical patients at MS center; 106 persons with MS from the community) completed objective assessments of neuropsychological function across cognitive domains. Exploratory factor analysis (EFA) was used to derive latent cognitive factor scores, and operationalize cognitive domain composite scores, to understand the unique, shared and redundant contribution of different cognitive domains to SDMT performance using hierarchical multiple regression and commonality analysis. ResultsAcross three independent samples we provide converging strong evidence that the cognitive domains of Memory, IPS and Rapid Automatized Naming (lexical access speed) jointly and uniquely contribute to SDMT performance. ConclusionThe SDMT measures multiple cognitive processes, which likely explains the high degree of sensitivity to cognitive change in MS. Researchers and clinicians should interpret the SDMT as a multifarious measure of general cognition rather than a specific test of IPS.

Chitosan and Chitin Deacetylase Activity Are Necessary for Development and Virulence of Ustilago maydis.

The biotrophic fungus Ustilago maydis harbors a chitin deacetylase (CDA) family of six active genes as well as one pseudogene which are differentially expressed during colonization. This includes one secreted soluble CDA (Cda4) and five putatively glycosylphosphatidylinositol (GPI)-anchored CDAs, of which Cda7 belongs to a new class of fungal CDAs. Here, we provide a comprehensive functional study of the entire family. While budding cells of U. maydis showed a discrete pattern of chitosan staining, biotrophic hyphae appeared surrounded by a chitosan layer. We purified all six active CDAs and show their activity on different chitin substrates. Single as well as multiple cda mutants were generated and revealed a virulence defect for mutants lacking cda7 We implicated cda4 in production of the chitosan layer surrounding biotrophic hyphae and demonstrated that the loss of this layer does not reduce virulence. By combining different cda mutations, we detected redundancy as well as specific functions for certain CDAs. Specifically, certain combinations of mutations significantly affected virulence concomitantly with reduced adherence, appressorium formation, penetration, and activation of plant defenses. Attempts to inactivate all seven cda genes simultaneously were unsuccessful, and induced depletion of cda2 in a background lacking the other six cda genes illustrated an essential role of chitosan for cell wall integrity.IMPORTANCE The basidiomycete Ustilago maydis causes smut disease in maize, causing substantial losses in world corn production. This nonobligate pathogen penetrates the plant cell wall with the help of appressoria and then establishes an extensive biotrophic interaction, where the hyphae are tightly encased by the plant plasma membrane. For successful invasion and development in plant tissue, recognition of conserved fungal cell wall components such as chitin by the plant immune system needs to be avoided or suppressed. One strategy to achieve this lies in the modification of chitin to chitosan by chitin deacetylases (CDAs). U. maydis has seven cda genes. This study reveals discrete as well as redundant contributions of these genes to virulence as well as to cell wall integrity. Unexpectedly, the inactivation of all seven genes is not tolerated, revealing an essential role of chitosan for viability.

Nonlinearity and Multivariate Dependencies in the Terrestrial Leg of Land‐Atmosphere Coupling

AbstractMost studies of land‐atmosphere coupling have focused on bivariate linear statistics like correlation. However, more complex dependencies exist, including nonlinear relationships between components of land‐atmosphere coupling and the transmutability of relationships between soil moisture and surface heat fluxes under different environmental conditions. In this study, a technique called multivariate mutual information, based on information theory, is proposed to quantify how surface heat fluxes depend on both surface energy and wetness conditions, that is, net radiation and soil moisture, seasonally across the globe using reanalysis data. Such interdependency is then decomposed into linear and nonlinear contributions, which are further decomposed as different components explainable as the unique contribution from individual surface conditions, redundant contributions shared by both surface conditions, and the synergistic contribution from the concurrent action of net radiation and soil moisture. In reanalysis data, the dependency linearly contributed from soil moisture bears a similar global pattern to previously identified hot spots of coupling. The linear unique contributions of net radiation and soil moisture are mainly nonoverlapping, which suggests two separate regimes are governed by either energy or water limitations. These patterns persist when the nonlinearity is superimposed, thus reinforcing the validity of the land‐atmospheric coupling hot spot paradigm and the spatial division of energy‐limited as well as water‐limited regions. Nevertheless, strong nonlinear relationships are detected, particularly over subtropical regions. Synergistic components are found across the globe, implying widespread multidimensional physical relationships among net radiation, soil moisture, and surface heat fluxes that previously had only been inferred locally.

An Improved Posteriori Variance-Covariance Components Estimation Applied to Unconventional GPS and Multiple Low-Cost Imus Integration Strategy

Meliorating a priori stochastic model of Kalman filer (KF) is always challenging. To address this challenge, this paper simultaneously estimates and corrects the variance components for all of the process noise and measurement matrix ( $\boldsymbol {Q}$ & $\boldsymbol {R}$ ) by a posteriori variance-covariance components estimation (VCE) algorithm, which makes the most of the process noise residuals and measurement residuals and measurement redundancy contribution. Unsurprisingly, in the conventional error states-based integration mechanization, the stochastic model tuning is not easy for IMU because of the error measurements between the observables from inertial sensors and other aiding sensors. This research utilizes an unconventional multi-sensor integration strategy, in which a 3D kinematic trajectory model is deployed as the main part of system equation and the systematic errors of each IMU and the measurements of all sensors are individually modelled. Furthermore, the weights of measurements from each inertial sensor are defined on the basis of the posterior variances, so that we could properly distribute the function of each measurement in the fusion algorithm. A real dataset involving GPS and multiple IMUs is processed to validate the proposed posteriori VCE algorithm by applying the unconventional integration strategy.

Effects of vowel context and discriminability on band independence in nonsense syllable recognition.

The Speech Intelligibility Index algorithm [(1997). ANSI S3.5-1997] models cues in disjoint frequency bands for consonants and vowels as additive, independent contributions to intelligibility. Data from other studies examining only consonants in single-vowel nonsense stimuli exhibit synergetic and redundant band contributions that challenge the band independence assumption. The present study tested the hypotheses that (a) band independence is present for multi-vowel stimuli, and (b) dependent band contributions are artifacts of confounding stimulus administration and testing methods. Data were measured in two experiments in which subjects identified filtered nonsense consonant-vowel-consonant syllables using a variety of randomly selected vowels. The measured data were used in simulations that further characterized the range of subject responses. Results of testing and simulation suggest that, where present, band independence is fostered by low broadband error, high vowel diversity, and high vowel discriminability. Synergistic band contributions were observed for confusable vowels that were most susceptible to filtering; redundant contributions were observed for the least susceptible vowels. Implications for intelligibility prediction and enhancement are discussed.

The TLR4 Agonist Monophosphoryl Lipid A Drives Broad Resistance to Infection via Dynamic Reprogramming of Macrophage Metabolism.

Monophosphoryl lipid A (MPLA) is a clinically used TLR4 agonist that has been found to drive nonspecific resistance to infection for up to 2 wk. However, the molecular mechanisms conferring protection are not well understood. In this study, we found that MPLA prompts resistance to infection, in part, by inducing a sustained and dynamic metabolic program in macrophages that supports improved pathogen clearance. Mice treated with MPLA had enhanced resistance to infection with Staphylococcus aureus and Candida albicans that was associated with augmented microbial clearance and organ protection. Tissue macrophages, which exhibited augmented phagocytosis and respiratory burst after MPLA treatment, were required for the beneficial effects of MPLA. Further analysis of the macrophage phenotype revealed that early TLR4-driven aerobic glycolysis was later coupled with mitochondrial biogenesis, enhanced malate shuttling, and increased mitochondrial ATP production. This metabolic program was initiated by overlapping and redundant contributions of MyD88- and TRIF-dependent signaling pathways as well as downstream mTOR activation. Blockade of mTOR signaling inhibited the development of the metabolic and functional macrophage phenotype and ablated MPLA-induced resistance to infection in vivo. Our findings reveal that MPLA drives macrophage metabolic reprogramming that evolves over a period of days to support a macrophage phenotype highly effective at mediating microbe clearance and that this results in nonspecific resistance to infection.

Growth condition dependency is the major cause of non-responsiveness upon genetic perturbation.

Investigating the role and interplay between individual proteins in biological processes is often performed by assessing the functional consequences of gene inactivation or removal. Depending on the sensitivity of the assay used for determining phenotype, between 66% (growth) and 53% (gene expression) of Saccharomyces cerevisiae gene deletion strains show no defect when analyzed under a single condition. Although it is well known that this non-responsive behavior is caused by different types of redundancy mechanisms or by growth condition/cell type dependency, it is not known what the relative contribution of these different causes is. Understanding the underlying causes of and their relative contribution to non-responsive behavior upon genetic perturbation is extremely important for designing efficient strategies aimed at elucidating gene function and unraveling complex cellular systems. Here, we provide a systematic classification of the underlying causes of and their relative contribution to non-responsive behavior upon gene deletion. The overall contribution of redundancy to non-responsive behavior is estimated at 29%, of which approximately 17% is due to homology-based redundancy and 12% is due to pathway-based redundancy. The major determinant of non-responsiveness is condition dependency (71%). For approximately 14% of protein complexes, just-in-time assembly can be put forward as a potential mechanistic explanation for how proteins can be regulated in a condition dependent manner. Taken together, the results underscore the large contribution of growth condition requirement to non-responsive behavior, which needs to be taken into account for strategies aimed at determining gene function. The classification provided here, can also be further harnessed in systematic analyses of complex cellular systems.

Pif1-family helicases cooperatively suppress widespread replication-fork arrest at tRNA genes.

Saccharomyces cerevisiae encodes two distinct Pif1-family helicases – Pif1 and Rrm3 – which have been reported to play distinct roles in numerous nuclear processes. Here, we systematically characterize the roles of Pif1 helicases in replisome progression and lagging-strand synthesis in S. cerevisiae. We demonstrate that either Pif1 or Rrm3 redundantly stimulate strand-displacement by DNA polymerase δ during lagging-strand synthesis. By analyzing replisome mobility in pif1 and rrm3 mutants, we show that Rrm3, with a partially redundant contribution from Pif1, suppresses widespread terminal arrest of the replisome at tRNA genes. Although both head-on and codirectional collisions induce replication fork arrest at tRNA genes, head-on collisions arrest a higher proportion of replisomes. Consistent with this observation, we find that head-on collisions between tRNA transcription and replication are under-represented in the S. cerevisiae genome. We demonstrate that tRNA-mediated arrest is R-loop independent, and propose that replisome arrest and DNA damage are mechanistically separable.

Redundant contribution of a Transient Receptor Potential cation channel Member 1 exon 11 single nucleotide polymorphism to equine congenital stationary night blindness.

BackgroundCongenital stationary night-blindness (CSNB) is a recessive autosomal defect in low-light vision in Appaloosa and other horse breeds. This condition has been mapped by linkage analysis to a gene coding for the Transient Receptor Potential cation channel Member 1 (TRPM1). TRPM1 is normally expressed in the ON-bipolar cells of the inner nuclear layer of the retina. Down-regulation of TRPM1 expression in CSNB results from a transposon-like insertion in intron 1 of the TRPM1 gene. Stop transcription signals in this transposon significantly reduce TRPM1 primary transcript levels in CSNB horses. This study describes additional contributions by a second mutation of the TRPM1 gene, the ECA1 108,249,293 C > T SNP, to down-regulation of transcription of the TRPM1 gene in night-blind horses. This TRPM1 SNP introduces a consensus binding site for neuro-oncological ventral antigen 1 (Nova-1) protein in the primary transcript. Nova-1 binding disrupts normal splicing signals, producing unstable, non-functional mRNA transcripts.ResultsRetinal bipolar cells express both TRPM1 and Nova-1 proteins. In vitro addition of Nova-1 protein retards electrophoretic migration of TRPM1 RNA containing the ECA1 108,249,293 C > T SNP. Up-regulating Nova-1 expression in primary cultures of choroidal melanocytes carrying the intron 11 SNP caused an average log 2-fold reduction of ~6 (64-fold) of TRPM1 mRNA expression.ConclusionsThese finding suggest that the equine TRPM1 SNP can act independently to reduce survival of TRPM1 mRNA escaping the intron 1 transcriptional stop signals in CSNB horses. Coexistence and co-inheritance of two independent TRPM1 mutations across 1000 equine generations suggests a selective advantage for the apparently deleterious CSNB trait.

Research Exploit from Bench and Shelve to Real Life Application

Findings prowess of young researchers and seniors appears to have been halted by feudal policies of established global governments or academic institutions which by all manner of means make uselessness of time and effort allotted to the research enterprise during conduct of high quality research, lack of political will or technocrats petulance attitude in research institutions have evolved arrays of paper works of applicable research on shelves or on benches in store room, libraries and offices, given the magnitude of global problems and limited number of solutions, these ideas should be transformed to usable forms. The review considers, benefits of applicable research, factors that militate against research transformation from paper work to pragmatic output in government or private sector, again apt policy frame work that could give impetus to researchers at local and international faced of academic or company base research enterprise was suggested in lieu of reoccurring unending problems of mankind, presumably, effective assimilation of these institutionalized redundant contributions to the very fabric of glaring glaciers of societal problems, may in passing, create egalitarian social structure, for assuredly. I hasten not to posit that, solutions in the “stored” redundant research works are the mainstay of equitable resource distribution, this is true, if by logical verbosity, solutions in them turn resources scarcity to resource abundant, it could be surmised that all of mankind struggle consist in plethora resources, resource lack or abundance at any given period in time, consequently I show by review, measures needed to justify time, money, and energy invested in the research conduct so as to diminished societal problems to barest minimum and turn research reports to real life applicable tools.

Redundancy and interaction of thrombin- and collagen-mediated platelet activation in tail bleeding and carotid thrombosis in mice.

Current antiplatelet strategies to prevent myocardial infarction and stroke are limited by bleeding risk. A better understanding of the roles of distinct platelet-activating pathways is needed. We determined whether platelet activation by 2 key primary activators, thrombin and collagen, plays distinct, redundant, or interacting roles in tail bleeding and carotid thrombosis in mice. Platelets from mice deficient for the thrombin receptor protease-activated receptor-4 (Par4) and the collagen receptor glycoprotein VI protein (GPVI) lack responses to thrombin and collagen, respectively. We examined tail bleeding and FeCl3-induced carotid artery occlusion in mice lacking Par4, GPVI, or both. We also examined a series of Par mutants with increasing impairment of thrombin signaling in platelets. Ablation of thrombin signaling alone by Par4 deficiency increased blood loss in the tail bleeding assay and impaired occlusive thrombus formation in the carotid occlusion assay. GPVI deficiency alone had no effect. Superimposing GPVI deficiency on Par4 deficiency markedly increased effect size in both assays. In contrast to complete ablation of thrombin signaling, 9- and 19-fold increases in EC50 for thrombin-induced platelet activation had only modest effects. The observation that loss of Par4 uncovered large effects of GPVI deficiency implies that Par4 and GPVI made independent, partially redundant contributions to occlusive thrombus formation in the carotid and to hemostatic clot formation in the tail under the experimental conditions examined. At face value, these results suggest that thrombin- and collagen-induced platelet activation can play partially redundant roles, despite important differences in how these agonists are made available to platelets.

Kinematic design of a redundant parallel mechanism for maskless lithography optical instrument manipulations

A new precision parallel mechanism having actuation redundancy will be introduced in this paper. Physical contribution of the actuation redundancy for the precision parallel mechanism is reviewed. In addition, several kinematic configurations have been analyzed for degrees of freedom verification and actuation redundancy. A new kinematic configuration which is 4-[P P]PS is suggested. The suggested 4-[P P]PS mechanism which has actuation redundancy provides six degrees of freedom to the mobile platform. For position control and path planning of the mobile platform, the inverse and the forward kinematics are solved for closed-form solutions. In order to verify the inverse and the forward kinematics, a numerical simulation result is presented. In addition to the inverse and forward accuracy proof, the numerical analysis provides other information such as independent translation motion, calibrated rotation arm at tilting motion, and symmetric motion at rotating motion.

Absence of B Cells Does Not Compromise Intramembranous Bone Formation during Healing in a Tibial Injury Model

Previous studies have generated conflicting results regarding the contribution of B cells to bone formation during physiology and repair. Here, we have investigated the role of B cells in osteoblast-mediated intramembranous anabolic bone modeling. Immunohistochemistry for CD45 receptor expression indicated that B cells had no propensity or aversion for endosteal regions or sites of bone modeling and/or remodeling in wild-type mice. In the endocortical diaphyseal region, quantitative immunohistology demonstrated that young wild-type and B-cell deficient mice had similar amounts of osteocalcin(+) osteoblast bone modeling surface. The degree of osteoblast-associated osteomac canopy was also comparable in these mice inferring that bone modeling cellular units were preserved in the absence of B cells. In a tibial injury model, only rare CD45 receptor positive B cells were located within areas of high anabolic activity, including minimal association with osterix(+) osteoblast-lineage committed mesenchymal cells in wild-type mice. Quantitative immunohistology demonstrated that collagen type I matrix deposition and macrophage and osteoclast distribution within the injury site were not compromised by the absence of B cells. Overall, osteoblast distribution during normal growth and bone healing via intramembranous ossification proceeded normally in the absence of B cells. These observations support that in vivo, these lymphoid cells have minimal influence, or at most, make redundant contributions to osteoblast function during anabolic bone modeling via intramembranous mechanisms.

Enabling Large-Scale Deliberation Using Attention-Mediation Metrics

Humanity now finds itself faced with a range of highly complex and controversial challenges – such as climate change, the spread of disease, international security, scientific collaborations, product development, and so on – that call upon us to bring together large numbers of experts and stakeholders to deliberate collectively on a global scale. Collocated meetings can however be impractically expensive, severely limit the concurrency and thus breadth of interaction, and are prone to serious dysfunctions such as polarization and hidden profiles. Social media such as email, blogs, wikis, chat rooms, and web forums provide unprecedented opportunities for interacting on a massive scale, but have yet to realize their potential for helping people deliberate effectively, typically generating poorly-organized, unsystematic and highly redundant contributions of widely varying quality. Large-scale argumentation systems represent a promising approach for addressing these challenges, by virtue of providing a simple systematic structure that radically reduces redundancy and encourages clarity. They do, however, raise an important challenge. How can we ensure that the attention of the deliberation participants is drawn, especially in large complex argument maps, to where it can best serve the goals of the deliberation? How can users, for example, find the issues they can best contribute to, assess whether some intervention is needed, or identify the results that are mature and ready to “harvest”? Can we enable, for large-scale distributed discussions, the ready understanding that participants typically have about the progress and needs of small-scale, collocated discussions?This paper will address these important questions, discussing (1) the strengths and limitations of current deliberation technologies, (2) how argumentation technology can help address these limitations, and (3) how we can use attention-mediation metrics to enhance the effectiveness of large-scale argumentation-based deliberations.