bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement- and inflammasome-mediated autoinflammation-paroxysmal nocturnal hemoglobinuria
Authors: Hoechsmann Britta , Murakami Yoshiko , Osato Makiko , Knaus Alexej , Kawamoto Michi , Inoue Norimitsu , Hirata Tetsuya , Murata Shogo , Anliker Markus , Eggerman Thomas , Jaeger Marten , Floettmann Ricarda , Hoellein Alexander , Murase Sho , Ueda Yasutaka , Nishimura Jun-ichi , Kanakura Yuzuru , Kohara Nobuo , Schrezenmeier Hubert , Krawitz Peter M. , Kinoshita Taroh 
Published: May 2019

AbstractParoxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder characterized by complement-mediated hemolysis and thrombosis, and bone marrow failure. Affected cells harbor somatic mutation in X-linkedPIGAgene, essential for the initial step in glycosylphosphatidylinositol (GPI) biosynthesis. Loss of GPI biosynthesis results in defective cell-surface expression of GPI-anchored complement regulators CD59 and DAF. The affected stem cells generate many abnormal blood cells after clonal expansion, which occurs under bone marrow failure. Here, we report the mechanistic basis of a disease entity, autoinflammation-paroxysmal nocturnal hemoglobinuria (AIF-PNH), caused by germline mutation plus somatic loss ofPIGTon chromosome 20q. A region containing maternally imprinted genes implicated in clonal expansion in 20q-myeloproliferative syndromes was lost together with normalPIGTfrom paternal chromosome 20. Taking these findings together with a lack of bone marrow failure, the mechanisms of clonal expansion in AIF-PNH appear to differ from those in PNH. AIF-PNH is characterized by intravascular hemolysis and recurrent autoinflammation, such as urticaria, arthralgia, fever and aseptic meningitis. Consistent with PIGT’s essential role in synthesized GPI’s attachment to precursor proteins, non-protein-linked free GPIs appeared on the surface of PIGT-defective cells. PIGT-defective THP-1 cells accumulated higher levels of C3 fragments and C5b-9 complexes, and secreted more IL-1β than PIGA-defective cells after activation of the complement alternative pathway. IL-1β secretion was dependent upon C5b-9 complexes, accounting for the effectiveness of the anti-C5 drug eculizumab for both intravascular hemolysis and autoinflammation. These results suggest that free GPIs enhance complement activation and inflammasome-mediated IL-1β secretion.
Operating Characteristics of the Rank-Based Inverse Normal Transformation for Quantitative Trait Analysis in Genome-Wide Association Studies
Authors: McCaw Zachary R. , Lane Jacqueline M. , Saxena Richa , Redline Susan , Lin Xihong 
Published: May 2019

SummaryQuantitative traits analyzed in Genome-Wide Association Studies (GWAS) are often non-normally distributed. For such traits, association tests based on standard linear regression are subject to reduced power and inflated type I error in finite samples. Applying the rank-based Inverse Normal Transformation (INT) to non-normally distributed traits has become common practice in GWAS. However, the different variations on INT-based association testing have not been formally defined, and guidance is lacking on when to use which approach. In this paper, we formally define and systematically compare the direct (D-INT) and indirect (I-INT) INT-based association tests. We discuss their assumptions, underlying generative models, and connections. We demonstrate that the relative powers of D-INT and I-INT depend on the underlying data generating process. Since neither approach is uniformly most powerful, we combine them into an adaptive omnibus test (O-INT). O-INT is robust to model misspecification, protects the type I error, and is well powered against a wide range of non-normally distributed traits. Extensive simulations were conducted to examine the finite sample operating characteristics of these tests. Our results demonstrate that, for non-normally distributed traits, INT-based tests outperform the standard untransformed association test (UAT), both in terms of power and type I error rate control. We apply the proposed methods to GWAS of spirometry traits in the UK Biobank. O-INT has been implemented in the R package RNOmni, which is available on CRAN.
Non-Uniformity of Projection Distributions Attenuates Resolution in Cryo-EM
Authors: Baldwin Philip R. , Lyumkis Dmitry 
Published: May 2019

AbstractVirtually every single-particle cryo-EM experiment currently suffers from specimen adherence to the air-water interface, leading to a non-uniform distribution in the set of projection views. Whereas it is well accepted that uniform projection distributions can lead to high-resolution reconstructions, non-uniform (anisotropic) distributions can negatively affect map quality, elongate structural features, and in some cases, prohibit interpretation altogether. Although some consequences of non-uniform sampling have been described qualitatively, we know little about how sampling quantitatively affects resolution in cryo-EM, especially given the numerous different projection schemes that can arise in experimental situations. Here, we show how inhomogeneity in any projection distribution scheme attenuates the global Fourier Shell Correlation (FSC) in relation to the number of particles and a single geometrical parameter, which we term the sampling compensation factor (SCF). The reciprocal of the SCF is defined as the average over Fourier shells of the reciprocal of the per-particle sampling and normalized to unity for uniform distributions. The SCF therefore ranges from one to zero, with values close to the latter implying large regions of poorly sampled or completely missing data in Fourier space. Using two synthetic test cases, influenza hemagglutinin and human apoferritin, we demonstrate how any amount of sampling inhomogeneity always attenuates the FSC compared to a uniform distribution. We advocate quantitative evaluation of the SCF criterion to approximate the effect of non-uniform sampling on resolution within experimental single-particle cryo-EM reconstructions.
The effect of NMDA-R antagonist, MK-801, on neuronal mismatch along the auditory thalamocortical pathway
Authors: Parras Gloria G , Valdés-Baizabal Catalina , Harms Lauren , Michie Patricia , Malmierca Manuel S 
Published: May 2019

ABSTRACTEfficient sensory processing requires that the brain is able to maximize its response to unexpected stimuli, while suppressing responsivity to expected events. Mismatch negativity (MMN) is an auditory event-related potential that occurs when a regular pattern is interrupted by an event that violates the expected properties of the pattern. MMN has been found to be reduced in individuals with schizophrenia in over 100 separate studies, an effect believed to be underpinned by glutamate N-methyl-D-aspartate receptor (NMDA-R) dysfunction, as it is observed that NMDA-R antagonists also reduce MMN in healthy volunteers. The aim of the current study is to examine this effect in rodents. Using single unit recording in specific auditory areas using methods not readily utilized in humans, we have previously demonstrated that neuronal indices of rodent mismatch responses recorded from thalamic and cortical areas of the brain can be decomposed into a relatively simple repetition suppression and a more sophisticated prediction error process. In the current study, we aimed to test how the NMDA-R antagonist, MK-801, affected both of these processes along the rat auditory thalamocortical pathway. We found that MK-801 had the opposite effect than expected, and enhanced thalamic repetition suppression and cortical prediction error. These single unit data correlate with the recordings of local field responses. Together with previous data, this study suggests that our understanding of the contribution of NMDA-R system to MMN generation is far from complete, and also has potential implications for future research in schizophrenia.Significance StatementIn this study, we demonstrate that an NMDA-R antagonist, MK-801, differentially affects single neuron responses to auditory stimuli along the thalamocortical axis by increasing the response magnitude of unexpected events in the auditory cortex and intensifying the adaptation of responses to expected events in the thalamus. Thus, we provide evidence that NMDA-R antagonists alter the balance between prediction-error and repetition suppression processes that underlie the generation of mismatch responses in the brain, and these effects are differentially expressed at different levels of auditory processing. As effects of MK-801 were in the opposite direction to our expectations, it demonstrates that our understanding of role of NMDA-R in synaptic plasticity and the neural processes underpinning MMN generation are far from complete.
Asymmetry in kinematic generalization between visual and passive lead-in movements are consistent with a forward model in the sensorimotor system
Authors: Howard Ian S. , Franklin Sae , Franklin David W. 
Published: May 2019

AbstractIn our daily life we often make complex actions comprised of linked movements, such as reaching for a cup of coffee and bringing it to our mouth to drink. Recent work has highlighted the role of such linked movements in the formation of independent motor memories, affecting the learning rate and ability to learn opposing force fields. In these studies, distinct prior movements (lead-in movements) allow adaptation of opposing dynamics on the following movement. Purely visual or purely passive lead-in movements exhibit different angular generalization functions of this motor memory as the lead-in movements are modified, suggesting different neural representations. However, we currently have no understanding of how different movement kinematics (distance, speed or duration) affect this recall process and the formation of independent motor memories. Here we investigate such kinematic generalization for both passive and visual lead-in movements to probe their individual characteristics. After participants adapted to opposing force fields using training lead-in movements, the lead-in kinematics were modified on random trials to test generalization. For both visual and passive modalities, recalled compensation was sensitive to lead-in duration and peak speed, falling off away from the training condition. However, little reduction in force was found with increasing lead-in distance. Interestingly, asymmetric transfer between lead-in movement modalities was also observed, with partial transfer from passive to visual, but very little vice versa. Overall these tuning effects were stronger for passive compared to visual lead-ins demonstrating the difference in these sensory inputs in regulating motor memories. Our results suggest these effects are a consequence of state estimation, with differences across modalities reflecting their different levels of sensory uncertainty arising as a consequence of dissimilar feedback delays.
Seasonal influenza: Modelling approaches to capture immunity propagation
Authors: Hill Edward M. , Petrou Stavros , de Lusignan Simon , Yonova Ivelina , Keeling Matt J. 
Published: May 2019

AbstractSeasonal influenza poses serious problems for global public health, being a significant contributor to morbidity and mortality. In England, there has been a long-standing national vaccination programme, with vaccination of at-risk groups and children offering partial protection against infection. Transmission models have been a fundamental component of analysis, informing the efficient use of limited resources. However, these models generally treat each season and each strain circulating within that season in isolation. Here, we amalgamate multiple data sources to calibrate a susceptible-latent-infected-recovered type transmission model for seasonal influenza, incorporating the four main strains and mechanisms linking prior season epidemiological out-comes to immunity at the beginning of the following season. Data pertaining to nine influenza seasons, starting with the 2009/10 season, informed our estimates for epidemiological processes, virological sample positivity, vaccine uptake and efficacy attributes, and general practitioner influenza-like-illness consultations as reported by the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We performed parameter inference via approximate Bayesian computation to assess strain transmissibility, dependence of present season influenza immunity on prior protection, and variability in the influenza case ascertainment across seasons. This produced reasonable agreement between model and data on the annual strain composition. Parameter fits indicated that the propagation of immunity from one season to the next is weaker if vaccine derived, compared to natural immunity from infection. Projecting the dynamics forward in time suggests that while historic immunity plays an important role in determining annual strain composition, the variability in vaccine efficacy hampers our ability to make long-term predictions.
Antecedents of entrepreneurial intentions amongst business students in a tertiary institution
Authors: Agolla Joseph Evans , Monametsi Gladness L. , Phera Petty 
Published: May 2019

Purpose
The purpose of this paper is to examine the antecedents of entrepreneurial intentions amongst open and distance learning students during employment crisis. To achieve the purpose of this study, Ajzen’s theory of planned behaviour (TPB) was applied and empirically tested on the sample population.

Design/methodology/approach
Data were taken from a sample of university students pursuing business-related courses in Open and Distance Learning mode. Self-reported questionnaires were handed to a total of 500 students to complete and return. Returned and usable questionnaires numbered 245 in total, giving a return rate of 49 per cent. Descriptive statistics and regression analyses were utilised to analyse data. Structural equation modelling incorporated into SPSS was used to assess the structural model.

Findings
The key finding reveal that Ajzen’s TPB can partially be applied in determining entrepreneurial intentions in the developing economy. The study results also revealed that perceived behavioural control, personal attitude and subjective norm (SN) explained 62.5 per cent of variations in entrepreneurial intention, which surpasses many other studies conducted previously.

Research limitations/implications
Present study relied on cross-sectional data using quantitative design, therefore limiting the full understanding of the causal relationship between variables.

Originality/value
The study developed a conceptual framework based on literature that was empirically tested, which adds to existing ones, thereby extending the literature in the field. Moreover, the study managed to incorporate SN as an intervening variable, which has rarely been done.
The fluidity of risk
Authors: Lewis James 
Published: May 2019

Purpose
Considered alone, risk is static; the purpose of this paper is to illustrate risk not as static but as a fluid condition dependent, for example, upon circumstances of its context in changeable vulnerability and behavioural responses of people facing risk.

Design/methodology/approach
Psychology provides strong evidence of behavioural response when facing hazards; technological disasters providing more evidence of behavioural responses to hazards and risk than response to disasters assumed to be “natural”. Initial and subsequent behavioural responses may critically affect ultimate outcomes. Post-event inquiries into technological disasters have revealed actions and inactions which created or aggravated subsequent consequences and their aftermath.

Findings
Decisions taken at a Japanese school between the 2011 earthquake and tsunami, and details of the 2017 fire at a tower-block in London, UK, indicate, in spite of training, that rigidity, uncertainty, hesitation or waver may affect critical decisions and their consequences. Pre- and post-disaster behaviour may not follow preferred patterns. Fear of imagined or real events may induce unanticipated denial of the reality of risk. Physical changes made after assessments of risk may not be recognised as affecting risk.

Research limitations/implications
Few published examples exist of public inquiries following disasters assumed to be from natural causes.

Practical implications
Reports of inquiries into technological disasters provide significant examples of behavioural responses which, if replicated, may influence outcomes of disasters labelled as “natural”.

Social implications
Awareness of risk as a fluid condition will facilitate realisation of effects upon risk of uncompleted or ongoing works, inappropriate behavioural responses, undeveloped resilience and of the need for regular reassessments of risk.

Originality/value
This study encourages comprehension of risk as an evolving and fluid condition.
A spatial and integrated flood risk diagnosis
Authors: Bennani Oumaima , Druon Ernest , Leone Frédéric , Tramblay Yves , Saidi Mohamed El Mehdi 
Published: May 2019

Purpose
The purpose of this paper is to identify vulnerable areas for flood hazard and to analyze stakes exposed in touristic valley of Morrocan mountains. The three goals are: methodological (low-cost diagnosis without starting data), operational (to show the risk and identify avenues of prevention in Ourika) and incentive (to reproduce this on other sectors in Morocco).

Design/methodology/approach
The vulnerability of three areas of the Ourika valley (the most frequented) was assessed by a hydro-geomorphological study, human frequentation surveys and risk indices at the building scale.

Findings
Surveys carried out in the field allowed the identification of areas with high risk, the evaluation of the buildings’ vulnerability and the frequentation of the valley. Evacuation plans, allowing easy access to potential refuges in case of flood, were finally proposed.

Originality/value
The reproducible, inexpensive and relevant nature of the approach (integrated and spatialized) helps in decision making and facilitating dialogue for prevention.
The direction of the response scale matters – accounting for the unit of measurement
Authors: Salzberger Thomas , Koller Monika 
Published: May 2019

PurposePsychometric analyses of self-administered questionnaire data tend to focus on items and instruments as a whole. The purpose of this paper is to investigate the functioning of the response scale and its impact on measurement precision. In terms of the response scale direction, existing evidence is mixed and inconclusive.Design/methodology/approachThree experiments are conducted to examine the functioning of response scales of different direction, ranging from agree to disagree versus from disagree to agree. The response scale direction effect is exemplified by two different latent constructs by applying the Rasch model for measurement.FindingsThe agree-to-disagree format generally performs better than the disagree-to-agree variant with spatial proximity between the statement and the agree-pole of the scale appearing to drive the effect. The difference is essentially related to the unit of measurement.Research limitations/implicationsA careful investigation of the functioning of the response scale should be part of every psychometric assessment. The framework of Rasch measurement theory offers unique opportunities in this regard.Practical implicationsBesides content, validity and reliability, academics and practitioners utilising published measurement instruments are advised to consider any evidence on the response scale functioning that is available.Originality/valueThe study exemplifies the application of the Rasch model to assess measurement precision as a function of the design of the response scale. The methodology raises the awareness for the unit of measurement, which typically remains hidden.
Shifting preservice teachers’ beliefs: toward critical connected learning
Authors: Struck Maggie , Rollag Yoon Stephanie 
Published: May 2019

PurposeThe purpose of this paper is to explore how preservice teacher’s beliefs change over time in a literacy methods elementary licensure course that encourages critical literacy and connects learning. The authors were interested in the interplay among identity, agency and structure within this process and how this connected with other literature on teacher beliefs and technology use.Design/methodology/approachUtilizing data from a larger ethnographic study and mediated discourse analysis (Scollon and Scollon, 2004), this paper follows preservice teacher’s use of digital tools and beliefs about using digital tools in the classroom over a semester-long hybrid course.FindingsFindings show changes in preservice teacher’s beliefs about technology use, interest-driven learning and her own agency. These changes were influenced by the framework of the course and course practices.Research limitations/implicationsThis research study offers practical ways to support preservice teachers’ implementation of digital tools with an emphasis on equity. Ultimately, preservice teachers’ experience shapes the opportunities students have with digital tools in schools.Practical implicationsRecognizing the competing discourses and pressures preservice teachers’ experience, the results of this study offer tools to support preservice teachers’ agency through the implementation of connected learning principles and critical literacy theories in preservice education courses, leading to the potential to expand equity in school settings.Originality/valueWhile there is research around connected learning in classrooms, there is limited research on a connected learning framework in preservice education programs. Additionally, this paper brings a new perspective on how pairing an emphasis of equity to a connected learning framework supports teachers’ implementation of digital tools.
Intra-organizational communication, understanding, and process diffusion in logistics service providers
Authors: Grawe Scott J. , Ralston Peter M. 
Published: May 2019

PurposeThe purpose of this paper is to investigate, using survey data, how a firm may be able to leverage innovation or processes specifically developed for one customer across its entire customer network using on-site, or implanted, employees.Design/methodology/approachData collected from a survey of 309 implanted logistics service provider (LSP) representatives are analyzed using structural equation modeling.FindingsThe findings show that intra-organizational task interdependence and face-to-face communication can lead to a greater understanding of firm processes developed for specific customers and greater diffusion of these new processes to other customers. Rather than separating customers that require implanted employees, these implants can be a conduit of valuable information and process enhancements that can positively impact a firm’s customer network.Originality/valueThe current research shows how LSPs can effectively use their customer networks to provide process improvements for multiple customers. Specifically, transferring processes between customers can lead to efficiencies and contribute to supply chain robustness not possible without process diffusion.