bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Health Interventions
Authors: Basu Sanjay
Published: November 2017

This chapter examines one of the most common and useful ways to understand complex public health and healthcare interventions: the Markov model. A Markov model is a representation of health or disease that expands well beyond the simple queuing model created in Chapter 4. In this chapter, the author uses Markov models to expand analysis to many more possible states, such as multiple stages of disease, to identify how effective or cost-effective our public health and healthcare programs might be. Markov models are highly flexible and allow for an infinite variety of diseases or interventions to be simulated and understood, which is why they are among the most popular tools for public health and healthcare research.
Practicing Techniques in Context
Authors: Basu Sanjay
Published: November 2017

Four major types of modeling were detailed in the preceding chapters. (1) The problem of resource allocation, which was extended to deal with the allocation of multiple resources in the context of multiple constraints. (2) Value of information problems, which ask how much should be paid to get more information to help with decision-making. (3) Queuing problems, which ask how to minimize waiting times for a service when demand is higher than supply. And (4), extending the simple “one-box” queuing model to a multibox Markov model, which determines how to estimate the incidence and prevalence of disease in a population given complex probabilities of getting the disease or being treated for it, and compares the effectiveness and cost-effectiveness of programs to address that disease. In this chapter, all four of these key modeling techniques will be examined in a common context: designing and evaluating a program to address a famine.
Preschool Assessment
Authors: Franz Carleen , Ascherman Lee , Shaftel Julia
Published: November 2017

This chapter describes the challenges that are unique to the assessment of the young child. A preschool child may not respond to standardized testing in a predictable way. A solid understanding of the developmental patterns of young children is necessary to accurately interpret evaluation results. The difficulties inherent in this process are described, as well as the benefits. The domains of the assessment process are outlined, including cognitive and learning ability, preacademic skill development, motor skills, and speech and language development. Issues related to behavior and attention are also addressed. Various approaches to preschool assessment are presented, including observational approaches in the natural setting as well as standardized testing, outlining benefits and cautions when working with this population.
Collaboration and Referral
Authors: Franz Carleen , Ascherman Lee , Shaftel Julia
Published: November 2017

The final chapter summarizes the benefits of clinician support for students and families who experience academic challenges and learning problems. A review of issues covered in this volume includes the definition of learning disability, challenges in understanding differences between school and external evaluations, differences in terminology, and the lack of congruence between parental expectations for schools and what schools may actually (and appropriately) offer. Recommendations for clinicians include the importance of obtaining a thorough academic history and consideration of school performance as a critical piece of the diagnostic and treatment picture. The impact of related disorders, such as ADHD and executive function deficits, is discussed. Clinicians are advised to become familiar with school-based legal requirements, evaluations, and identification procedures for the benefit of students and their parents.
Nerve physiology
Authors: Pitt Matthew
Published: November 2017

The chapter begins with a description of the normal findings in healthy sensory and motor nerves. The distribution of nerve fibres by diameter in the sensory nerve and its effect on the recorded action potential is outlined. The method by which velocity and compound muscle action potential are derived from motor stimulation follows. H-reflex studies and F-wave identification are described. A section on the strategies used for nerve conduction study in children and the nerves chosen for examination leads on to a description of the difficulties of deriving normative data in children. Next follows a detailed description of the findings in both sensory and motor nerves in demyelination where a distinction between patchy and homogenous demyelination is possible. An analysis of the nerve findings in axonal degeneration is then presented. The chapter finishes with a discussion of the variability in nerve testing.
Nerve damage and entrapment syndromes
Authors: Pitt Matthew
Published: November 2017

In this chapter, the pathological classification of nerve damage using the Sunderland classification is described. The neurophysiological findings that allow distinction between neurapraxia, axonotmesis, and neurotmesis are highlighted. Nerve entrapment syndromes involving the upper and lower limb are discussed according to the nerve involved, with particular emphasis on those commonly seen in children. In the upper limb, median, ulnar, and radial nerve entrapments are described with particular emphasis on the carpal tunnel syndrome in mucopolysaccharidosis. Also mentioned here are the thoracic outlet syndrome and neuralgic amyotrophy. In the leg, femoral nerve and sciatic nerve syndromes are discussed with particular emphasis on the differing aetiologies of sciatic nerve palsy in children.
More advanced techniques
Authors: Pitt Matthew
Published: November 2017

This chapter covers some of the less common, more advanced techniques which will be demanded of the paediatric electromyographer. Diaphragmatic function can be assessed by phrenic nerve studies with, on occasion, additional information from diaphragmatic electromyography (EMG) approached from the transcostal route. Tests of cranial nerves are covered including blink reflexes, and studies that can be used for the investigation of swallowing and sucking abnormalities. Also discussed are investigations for abnormalities of the face including congenital facial palsy either acquired congenitally or when it is acquired outside of the neonatal period. The chapter concludes with a section on the EMG investigation of obstetric brachial plexus palsy.
Non-linear acceleration at supernova remnant shocks and the hardening in the cosmic ray spectrum
Authors: Recchia S , Gabici S
Published: November 2017

In the last few years, several experiments have shown that the cosmic ray spectrum below the knee is not a perfect power law. In particular, the proton and helium spectra show a spectral hardening by ∼0.1–0.2 in spectral index at particle energies of ∼ 200–300 GeV nucleon−1. Moreover, the helium spectrum is found to be harder than that of protons by ∼0.1 and some evidence for a similar hardening was also found in the spectra of heavier elements. Here, we consider the possibility that the hardening may be the result of a dispersion in the slope of the spectrum of cosmic rays accelerated at supernova remnant shocks. Such a dispersion is indeed expected within the framework of non-linear theories of diffusive shock acceleration, which predict steeper (harder) particle spectra for larger (smaller) cosmic ray acceleration efficiencies.
Germline SUFU mutation carriers and medulloblastoma: clinical characteristics, cancer risk, and prognosis
Authors: Guerrini-Rousseau Léa , Dufour Christelle , Varlet Pascale , Masliah-Planchon Julien , Bourdeaut Franck , Guillaud-Bataille Marine , Abbas Rachid , Bertozzi Anne-Isabelle , Fouyssac Fanny , Huybrechts Sophie , Puget Stéphanie , Bressac-De Paillerets Brigitte , Caron Olivier , Sevenet Nicolas , Dimaria Marina , Villebasse Sophie , Delattre Olivier , Valteau-Couanet Dominique , Grill Jacques , Brugières Laurence
Published: November 2017

Background

Germline mutations of suppressor of fused homolog (SUFU) predispose to sonic hedgehog (SHH) medulloblastoma. Germline SUFU mutations have been reported in nevoid basal cell carcinoma syndrome (NBCCS), but little is known about the cancer risk and clinical spectrum.

Methods

We performed a retrospective review of all patients with medulloblastoma and a germline SUFU mutation in France.

Results

Twenty-two patients from 17 families were identified with medulloblastoma and a germline SUFU mutation (median age at diagnosis: 16.5 mo). Macrocrania was present in 20 patients, but only 5 met the diagnostic criteria for NBCCS. Despite treatment with surgery and chemotherapy, to avoid radiotherapy in all patients except one, the outcome was worse than expected for SHH medulloblastoma, due to the high incidence of local relapses (8/22 patients) and second malignancies (n = 6 in 4/22 patients). The 5-year progression-free survival and overall survival rates were 42% and 66%. Mutations were inherited in 79% of patients, and 34 additional SUFU mutation carriers were identified within 14 families. Medulloblastoma penetrance was incomplete, but higher than in Patched 1 (PTCH1) mutation carriers. Besides medulloblastoma, 19 other tumors were recorded among the 56 SUFU mutation carriers, including basal cell carcinoma (BCC) in 2 patients and meningioma in 3 patients.

Conclusion

Germline SUFU mutations strongly predispose to medulloblastoma in the first years of life, with worse prognosis than usually observed for SHH medulloblastoma. The clinical spectrum differs between SUFU and PTCH1 mutation carriers, and BCC incidence is much lower in SUFU mutation carriers. The optimal treatment of SUFU mutation–associated medulloblastoma has not been defined.
Genome characterization of Turkey Rotavirus G strains from the United States identifies potential recombination events with human Rotavirus B strains
Authors: Chen Fangzhou , Knutson Todd P. , Porter Robert E. , Ciarlet Max , Mor Sunil Kumar , Marthaler Douglas G.
Published: November 2017

Rotavirus G (RVG) strains have been detected in a variety of avian species, but RVG genomes have been published from only a single pigeon and two chicken strains. Two turkey RVG strains were identified and characterized, one in a hatchery with no reported health issues and the other in a hatchery with high embryo/poult mortality. The two turkey RVG strains shared only an 85.3 % nucleotide sequence identity in the VP7 gene while the other genes possessed high nucleotide identity among them (96.3–99.9 %). Low nucleotide percentage identities (31.6–87.3 %) occurred among the pigeon and chicken RVG strains. Interestingly, potential recombination events were detected between our RVG strains and a human RVB strain, in the VP6 and NSP3 segments. The epidemiology of RVG in avian flocks and the pathogenicity of the two different RVG strains should be further investigated to understand the ecology and impact of RVG in commercial poultry flocks.
Single cell transcriptomics of regulatory T cells reveals trajectories of tissue adaptation
Authors: Miragaia Ricardo J , Gomes Tomás , Chomka Agnieszka , Jardine Laura , Riedel Angela , Hegazy Ahmed N. , Lindeman Ida , Emerton Guy , Krausgruber Thomas , Shields Jacqueline , Haniffa Muzlifah , Powrie Fiona , Teichmann Sarah A.
Published: November 2017

Non-lymphoid tissues (NLTs) harbour a pool of adaptive immune cells, the development and phenotype of which remains largely unexplored. Here, we used single-cell RNA-seq to characterise CD4+regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, the respective draining lymph nodes and spleen. From this data, we modelled a continuous lymphoid-to-NLT trajectory for Treg, and reconstructed the mechanisms of cell migration and NLT adaption. This revealed a shared transcriptional programme of NLT priming in both skin and colon-associated lymph nodes, followed by tissue-specific adaptation. Predicted migration kinetics were validated using a melanoma-induction model, emphasizing the relevance of key regulators and receptors, includingBatf, Rora, Ccr8, Samsn1. Finally, we profiled human blood and NLT Treg and Tmem cells, identifying cross-mammalian conserved tissue signatures. In summary, we have identified molecular signals mediating NLT Treg recruitment and tissue adaptation through the combined use of computational prediction andin vivovalidation.
BMPR2 inhibits activin- and BMP-signaling via wild type ALK2
Authors: Olsen Oddrun Elise , Sankar Meenu , Elsaadi Samah , Hella Hanne , Buene Glenn , Darvekar Sagar Ramesh , Misund Kristine , Katagiri Takenobu , Holien Toril
Published: November 2017

Activin A is a member of the TGF-β superfamily and activates the transcription factors SMAD2/3 through the ALK4 type 1 receptor. Activin A has also been shown to activate SMAD1/5/8 through mutated variants of the type 1 receptor ALK2. Interestingly, we here show that both activin A and activin B could activate SMAD1/5/8 through endogenous wild type ALK2 in multiple myeloma cells. Knockdown of the type 2 receptor BMPR2 strongly potentiated activin A- and activin B-induced SMAD1/5/8 activation and subsequent cell death. Furthermore, activity of BMP6, BMP7 or BMP9, which also signal via ALK2, was potentiated by BMPR2 knockdown. Similar results were seen in HepG2 liver carcinoma cells. We propose that BMPR2 inhibited ALK2-mediated signaling by preventing ALK2 from oligomerizing with the type 2 receptors ACVR2A and ACVR2B, necessary for ALK2 activation by activins and several BMPs in these cells. In conclusion, BMPR2 could be explored as a possible target for therapy in patients with multiple myeloma.

Summary Statement

The activation of SMAD1/5/8 via endogenous wild type ALK2 by activin A, activin B, and certain BMPs was enhanced when BMPR2 levels were knocked down.
Bidirectional Cycling Dynamics of Living Neuronal Networksin Vitro
Authors: Gladkov Arseniy , Grinchuk Oleg , Yana Pigareva , Mukhina Irina , Kazantsev Victor , Pimashkin Alexey
Published: November 2017

Phenomena of synchronization, rhythmogenesis and coherence found in brain networks are believed to be a dynamical substrate for cognitive functions such as learning and memory. However, it is still debated whether the rhythmic activity emerges from network morphology developed in neurogenesis or as a result of neuronal dynamics realized under certain conditions. In this research we found, that in neural networks formed in mature hippocampal cultures with high cellular density the spiking activity self-organized and converged to long, complex and rhythmically repeated superbursts. The superburst lasted tens of seconds and consisted of hundreds of short (50-100 ms) small bursts with a high spiking rate of 139.0 ± 78.6 Hz that can be associated with high-frequency oscillations in the hippocampus. In turn, the interval between peak burst activities in the range of 100-150 ms can be treated as a theta rhythm (11.2 ± 1.5 Hz). Distribution of spikes within the bursts was non-random, representing a set of well-defined space-time base patterns or motifs. We found that the long superburst can be classified into two types. Each type was associated with a unique direction of spike propagation and, hence, can be encoded by a binary sequence with random switching between the two “functional” states. Such precisely structured bidirectional rhythmic activity developed in self-organizing cultured networks were quite similar to what observed in thein vivoexperiments.
Blind prediction of noncanonical RNA structure at atomic accuracy
Authors: Watkins Andrew , Geniesse Caleb , Kladwang Wipapat , Zakrevsky Paul , Jaeger Luc , Das Rhiju
Published: November 2017

Prediction of RNA structure from nucleotide sequence remains an unsolved grand challenge of biochemistry and requires distinct concepts from protein structure prediction. Despite extensive algorithmic development in recent years, modeling of noncanonical base pairs of new RNA structural motifs has not been achieved in blind challenges. We report herein a stepwise Monte Carlo (SWM) method with a unique add-and-delete move set that enables predictions of noncanonical base pairs of complex RNA structures. A benchmark of 82 diverse motifs establishes the method’s general ability to recover noncanonical pairs ab initio, including multistrand motifs that have been refractory to prior approaches. In a blind challenge, SWM models predicted nucleotide-resolution chemical mapping and compensatory mutagenesis experiments for three in vitro selected tetraloop/receptors with previously unsolved structures (C7.2, C7.10, and R1). As a final test, SWM blindly and correctly predicted all noncanonical pairs of a Zika virus double pseudoknot during a recent community-wide RNA-puzzle. Stepwise structure formation, as encoded in the SWM method, enables modeling of noncanonical RNA structure in a variety of previously intractable problems.
Efficient Flexible Backbone Protein-Protein Docking for Challenging Targets
Authors: Marze Nicholas A. , Roy Burman Shourya S. , Sheffler William , Gray Jeffrey J.
Published: November 2017

Computational prediction of protein-protein complex structures facilitates a fundamental understanding of biological mechanisms and enables therapeutics design. Binding-induced conformational changes challenge all current computational docking algorithms by exponentially increasing the conformational space to be explored. To restrict this search to relevant space, some computational docking algorithms exploit the inherent flexibility of the protein monomers to simulate conformational selection from pre-generated ensembles. As the ensemble size expands with increased protein flexibility, these methods struggle with efficiency and high false positive rates. Here, we develop and benchmark a method that efficiently samples large conformational ensembles of flexible proteins and docks them using a novel, six-dimensional, coarse-grained score function. A strong discriminative ability allows an eight-fold higher enrichment of nearnative candidate structures in the coarse-grained phase compared to a previous method. Further, the method adapts to the diversity of backbone conformations in the ensemble by modulating sampling rates. It samples 100 conformations each of the ligand and the receptor backbone while increasing computational time by only 20–80%. In a benchmark set of 88 proteins of varying degrees of flexibility, the expected success rate for blind predictions after resampling is 77% for rigid complexes, 49% for moderately flexible complexes, and 31% for highly flexible complexes. These success rates on flexible complexes are a substantial step forward from all existing methods. Additionally, for highly flexible proteins, we demonstrate that when a suitable conformer generation method exists, RosettaDock 4.0 can dock the complex successfully.

Significance

Predicting binding-induced conformational plasticity in protein backbones remains a principal challenge in computational protein–protein docking. To date, there are no methods that can reliably dock proteins that undergo more than 1 Å root-mean-squared-deviation of the backbones of the interface residues upon binding. Here, we present a method that samples backbone motions and scores conformations rapidly, obtaining–for the first time–successful docking of nearly 50% of flexible target complexes with backbone conformational change up to 2.2 Å RMSD. This method will be applicable to a broader range of protein docking problems, which in turn will help us understand biomolecular assembly and protein function.
Variance reduction for antithetic integral control of stochastic reaction networks
Authors: Briat Corentin , Gupta Ankit , Khammash Mustafa
Published: November 2017

The antithetic integral feedback motif recently introduced in [6] is known to ensure robust perfect adaptation for the mean dynamics of a given molecular species involved in a complex stochastic biomolecular reaction network. However, it was observed that it also leads to a higher variance in the controlled network than that obtained when using a constitutive (i.e. open-loop) control strategy. This was interpreted as the cost of the adaptation property and may be viewed as a performance deterioration for the overall controlled network. To decrease this variance and improve the performance, we propose to combine the antithetic integral feedback motif with a negative feedback strategy. Both theoretical and numerical results are obtained. The theoretical ones are based on a tailored moment closure method allowing one to obtain approximate expressions for the stationary variance for the controlled network and predict that the variance can indeed be decreased by increasing the strength of the negative feedback. Numerical results verify the accuracy of this approximation and show that the controlled species variance can indeed be decreased, sometimes below its constitutive level. Three molecular networks are considered in order to verify the wide applicability of two types of negative feedback strategies. The main conclusion is that there is a trade-off between the speed of the settling-time of the mean trajectories and the stationary variance of the controlled species; i.e. smaller variance is associated with larger settling-time.

Author summary

Homeostasis, the ability of living organisms to regulate their internal state, is of fundamental importance for their adaptation to environmental changes and their survival. This is the reason why complex regulatory genetic networks evolved and allowed for the emergence of more and more complex organisms. Recently, the theoretical study of those regulatory networks using ideas and concepts from control theory and the design of novel ones have gained a lot of attention. Synthetic regulatory circuits are seen as elementary building blocks for the design of complex networks that need to incorporate some regulating elements to be fully functional. This is for instance the case in metabolic engineering where the production of biomolecules, such as drugs or biofuels, need to be optimized and tightly regulated. A particular circuit, the so-called antithetic integral controller, is now known to ensure homeostasis even when regulatory circuits are subject to randomness. However, it is also known that this circuit increases variability in the network. The effects of a correcting negative feedback loop on the variance are discussed here and it is shown that variability can be reduced this way. Notably, we show that there is a tradeoff between speed of the network and variability.
Aiptasia as a model to study metabolic diversity and specificity in cnidarian-dinoflagellate symbioses
Authors: Rädecker Nils , Raina Jean-Baptiste , Pernice Mathieu , Perna Gabriela , Guagliardo Paul , Kilburn Matt R , Aranda Manuel , Voolstra Christian R
Published: November 2017

The symbiosis between cnidarian hosts and microalgae of the genusSymbiodiniumprovides the foundation of coral reefs in oligotrophic waters. Understanding the nutrient-exchange between these partners is key to identifying the fundamental mechanisms behind this symbiosis. However, deciphering the individual role of host and algal partners in the uptake and cycling of nutrients has proven difficult, given the endosymbiotic nature of this relationship. In this study, we highlight the advantages of the emerging model system Aiptasia to investigate the metabolic diversity and specificity of cnidarian – dinoflagellate symbiosis. For this, we combined traditional measurements with nano-scale secondary ion mass spectrometry (NanoSIMS) and stable isotope labeling to investigate carbon and nitrogen cycling both at the organismal scale and the cellular scale. Our results suggest that the individual nutrient assimilation by hosts and symbionts depends on the identity of their respective symbiotic partner. Further,δ13C enrichment patterns revealed that alterations in carbon fixation rates only affected carbon assimilation in the cnidarian host but not the algal symbiont, suggesting a ‘selfish’ character of this symbiotic association. Based on our findings, we identify new venues for future research regarding the role and regulation of nutrient exchange in the cnidarian - dinoflagellate symbiosis. In this context, the model system approach outlined in this study constitutes a powerful tool set to address these questions.
Mechanochemical Coupling and Bi-Phasic Force-Velocity Dependence in the Ultra-Fast Ring ATPase SpoIIIE
Authors: Liu Ninning , Chistol Gheorghe , Cui Yuanbo , Bustamante Carlos
Published: November 2017

Multi-subunit ring-shaped ATPases are molecular motors that harness chemical free energy to perform vital mechanical tasks such as polypeptide translocation, DNA unwinding, and chromosome segregation. Previously we reported the intersubunit coordination and stepping behavior of the hexameric ring-shaped ATPase SpoIIIE (Liu et al., 2015). Here we use optical tweezers to characterize the motor’s mechanochemistry. Analysis of the motor response to external force at various nucleotide concentrations identifies phosphate release as the likely force-generating step. Analysis of SpoIIIE pausing indicates that pauses are off-pathway events. Characterization of SpoIIIE slipping behavior reveals that individual motor subunits engage DNA upon ATP binding. Furthermore, we find that SpolIIE’s velocity exhibits an intriguing bi-phasic dependence on force. We hypothesize that this behavior is an adaptation of ultra-fast motors tasked with translocating DNA from which they must also remove DNA-bound protein roadblocks. Based on these results, we formulate a comprehensive mechanochemical model for SpoIIIE.
Impacts of predators, habitat, recruitment, and disease on soft-shell clamsMya arenariaand stout razor clamsTagelus plebeiusin Chesapeake Bay
Authors: Glaspie Cassandra N. , Seitz Rochelle D. , Ogburn Matthew B. , Dungan Christopher F. , Hines Anson H.
Published: November 2017

Soft-shell clams,Mya arenaria, and razor clams,Tagelus plebeius, in Chesapeake Bay have declined since the 1970s, with severe declines since the 1990s. These declines are likely caused by multiple factors including warming, predation, habitat loss, recruitment limitation, disease, and harvesting. A bivalve survey in Chesapeake Bay examined influential factors on bivalve populations, focusing on predation (crabs, fish, and cownose rays), habitat (mud, sand, gravel, shell, or seagrass), environment (temperature, salinity, and dissolved oxygen), recruitment, and disease.M. arenariaandT. plebeiuswere found more often in habitats with complex physical structures (seagrass, shell) than any other habitat. Pulses in bivalve density associated with recruitment were attenuated through the summer and fall when predators are most active, indicating that predators likely influence temporal dynamics in these species. Presence ofMya arenaria,which is near the southern extent of its range in Chesapeake Bay, was negatively correlated with water temperature. Recruitment ofM. arenariain Rhode River, MD, declined between 1980 and 2016. Infection by the parasitic protistPerkinsussp. was associated with stressful environmental conditions, bivalve size, and environmental preferences ofPerkinsussp, but was not associated with bivalve densities. It is likely that habitat loss, low recruitment, and predators are major factors keepingT. plebeiusandM. arenariaat low densities in Chesapeake Bay. Persistence at low densities may be facilitated by habitat complexity (presence of physical structures), whereas further reductions in habitats such as seagrass and shell hash could result in local extinction of these important bivalve species.
Placenta DNA Methylation Adaptation to Maternal Glucose Tolerance in Pregnancy
Authors: Cardenas Andres , Gagné-Ouellet Valerie , Allard Catherine , Brisson Diane , Perron Patrice , Bouchard Luigi , Hivert Marie-France
Published: November 2017

Maternal hyperglycemia during pregnancy is associated with fetal growth and adverse perinatal and developmental outcomes. Placental epigenetic maladaptation may underlie these associations. We performed an epigenome-wide association study of term placentas and prenatal maternal glucose response 2-hour post oral glucose challenge at 24-30 weeks of gestation among 448 mother-infant pairs. Maternal glucose levels post-load were strongly associated with lower DNA methylation of 4 CpGs (FDR q<0.05) within the Phosphodiesterase 4B gene (PDE4B). Additionally, three other CpGs were differentially methylated relative to maternal glucose response within the TNFRSF1B; LDLR; and BLM genes (FDR q<0.05). Methylation levels correlated with expression in placental tissue for all 4 CpG sites in PDE4B (rs: 0.26–0.35, P<0.01), LDLR (rs: 0.22, P=0.03) and at TNFRSF1B (rs: -0.25, P=0.01). Our study provides evidence that maternal glucose response during pregnancy is associated with DNA methylation of genes within the placenta that are partially under epigenetic control.
EB1 binding provides a diffusion trap mechanism regulating STIM1 localization and Ca2+ signaling
Authors: Chang Chi-Lun , Chen Yu-Ju , Liou Jen
Published: November 2017

The endoplasmic reticulum (ER) Ca2+ sensor STIM1 forms oligomers and translocates to ER-plasma membrane (PM) junctions to activate store-operated Ca2+ entry (SOCE) following ER Ca2+ depletion. STIM1 also directly interacts with end binding protein 1 (EB1) at microtubule (MT) plus-ends and resembles comet-like structures during time-lapse imaging. Nevertheless, the role of STIM1-EB1 interaction in regulating SOCE remains unresolved. Using live-cell imaging combined with pharmacological perturbation and a reconstitution approach, we revealed that EB1 binding constitutes a diffusion trap mechanism restricting STIM1 targeting to ER-PM junctions. We further showed that STIM1 oligomers retain EB1 binding ability in ER Ca2+-depleted cells. EB1 binding delayed the translocation of STIM1 oligomers to ER-PM junctions and recaptured STIM1 to prevent excess SOCE and ER Ca2+ overload. Thus, the counterbalance of EB1 binding and PM targeting of STIM1 shapes the kinetics and amplitude of local SOCE in regions with growing MTs, and contributes to precise spatiotemporal regulation of Ca2+ signaling crucial for cellular functions and homeostasis.

STIM1 activates store-operated Ca2+ entry (SOCE) by translocating to endoplasmic reticulum-plasma membrane junctions. Chang et al. revealed that STIM1 localization and SOCE are regulated by a diffusion trap mechanism mediated by STIM1 binding to EB1 at growing microtubule ends.
Spliceosome profiling visualizes the operations of a dynamic RNPin vivoat nucleotide resolution
Authors: Burke Jordan E. , Longhurst Adam D. , Merkurjev Daria , Sales-Lee Jade , Rao Beiduo , Moresco James , Yates John , Li Jingyi Jessica , Madhani Hiten D.
Published: November 2017

Tools to understand how the spliceosome functionsin vivohave lagged behind advances in its structural biology. We describe methods to globally profile spliceosome-bound precursor, intermediates and products at nucleotide resolution. We apply these tools to three divergent yeast species that span 600 million years of evolution. The sensitivity of the approach enables detection of novel cases of non-canonical catalysis including interrupted, recursive and nested splicing. Employing statistical modeling to understand the quantitative relationships between RNA features and the data, we uncover independent roles for intron size, position and number in substrate progression through the two catalytic stages. These include species-specific inputs suggestive of spliceosome-transcriptome coevolution. Further investigations reveal ATP-dependent discard of numerous endogenous substrates at both the precursor and lariat-intermediate stages and connect discard to intron retention, a form of splicing regulation. Spliceosome profiling is a quantitative, generalizable global technology to investigate an RNP central to eukaryotic gene expression.

Highlights

Measurement of spliceosome-bound precursor and intermediate in three species

Non-canonical splicing events revealed

Statistical modeling uncovers substrate features that predict catalytic efficiency

Discard of suboptimal substrates occursin vivoand predicts intron-retained mRNAs
On-orbit frequency identification of spacecraft based on attitude maneuver data
Authors: Xie Yong , Liu Pan , Cai Guoping
Published: November 2017

Purpose

The purpose of this paper is to present an on-orbit frequency identification method for spacecraft directly using attitude maneuver data. Natural frequency of flexible solar arrays plays an important role in attitude control design of spacecraft with solar arrays, and its precision will directly affect the accuracy of attitude maneuver. However, when the flexibility of the solar arrays is large, because of air damping, gravity effect etc., the frequency obtained by ground test shows great error compared with the on-orbit real value. One solution to this problem is to conduct on-orbit identification during which proper identification methods are used to obtain the parameters of interest based on the real on-orbit data of spacecraft.

Design/methodology/approach

The observer/Kalman filter identification and eigensystem realization algorithm are used as identification methods, and the attitude maneuver controller is designed using the rigid-body dynamics method.

Findings

Two conclusions are drawn in this paper according to results of numerical simulations. The first one is that the attitude controller based on the rigid-body dynamics method is effective in attitude maneuver of the spacecraft. The second one is that the on-orbit parameter identification can be directly achieved by using attitude maneuver data of spacecraft without adding additional missions.

Practical implications

Based on the methods proposed in this paper, it is convenient to obtain the natural frequencies of the spacecraft using the data of the attitude maneuver, which may greatly reduce the cost of on-orbit identification test.

Originality/value

The way of obtaining natural frequencies based on attitude maneuver data of spacecraft provides high originality and value for practical application.
A simplified model for predicting the propeller-wing interaction
Authors: Huang Xianghua , Zhao Xiaochun , Huang Jiaqin
Published: November 2017

Purpose

The traditional numerical methods to predict the interaction between the wing and propeller are too complex and time-consuming for computation to a certain extent. Therefore, they are not applicable for a real-time integrated turboprop aircraft model. This paper aims to present a simplified model capable of high-precision and real-time computing.

Design/methodology/approach

A wing model based on the lifting line theory coupled with a propeller model based on the strip theory is used to predict the propeller-wing interaction. To meet the requirement of real-time computing, a novel decoupling parameter is presented to replace lifting line model (LLM) applied for wings with a simplified fitting model (FM).

Findings

The comparison between the LLM and the simplified FM demonstrates that the results of the FM have a good agreement with the results of the LLM, which means that the simplified FM has the advantages of both high-accuracy and real-time computation.

Practical implications

After simplification, the propeller-wing interaction model is suitable for a real-time integrated turboprop aircraft model.

Originality/value

A novel decoupling parameter is presented to replace LLM applied for wings with a simplified FM, which has the advantages of both high-accuracy and real-time computation.
Decentralized control for spacecraft formation in elliptic orbits
Authors: Wu Baolin , Cao Xibin
Published: November 2017

Purpose

This paper aims to address the problem of formation control for spacecraft formation in elliptic orbits by using local relative measurements.

Design/methodology/approach

A decentralized formation control law is proposed to solve the aforementioned problem. The control law for each spacecraft uses only its relative state with respect to the neighboring spacecraft it can sense. These relative states can be acquired by local relative measurements. The formation control problem is converted to n stabilization problems of a single spacecraft by using algebraic graph theories. The resulting relative motion model is described by a linear time-varying system with uncertain parameters. An optimal guaranteed cost control scheme is subsequently used to obtain the desired control performance.

Findings

Numerical simulations show the effectiveness of the proposed formation control law.

Practical implications

The proposed control law can be considered as an alternative to global positioning system-based relative navigation and control system for formation flying missions.

Originality/value

The proposed decentralized formation control architecture needs only local relative measurements. Fuel consumption is considered by using an optimal guaranteed cost control scheme.
Product market competition, state-ownership, corporate governance and firm performance
Authors: Liu Li , Qu Wen , Haman Janto
Published: November 2017

Purpose

The purpose of this paper is to examine the association between firm performance and product market competition (PMC), and then examine the mitigation effect of corporate governance and/or state-ownership (SOEs) in the association between PMC and firm performance using Chinese listed firms.

Design/methodology/approach

The authors consider three determinants of the PMC that affect the nature of competition, and use market concentration, product substitutability and market size as proxies for PMC. The authors construct a corporate governance index which measures the extent of board independence, monitoring strength of supervisory board over board of directors, and monitoring strength of board of directors over CEO. The authors use Tobin’s Q as a proxy for firm performance. The authors use a sample of 20,706 firm-year observations listed on the Chinese stock market between 2001 and 2016 to empirically investigate the research questions proposed in the paper.

Findings

The authors find that higher PMC is associated with lower firm performance. The authors find that good corporate governance practices moderate the negative effect of higher PMC on firm performance. The association between higher PMC and lower performance is weaker for firms controlled by SOEs compared to non-SOEs. Further, the moderation effect of SOEs on the association between higher PMC and lower performance is more pronounced for firms with good corporate governance practices compared to firms with weak corporate governance practices.

Originality/value

Extant studies investigating the relationship between PMC and corporate governance suggest an either complementary or substitution relationship in developed economies. Our study highlights the interactive role played by SOEs and good corporate governance practices in firm performance in highly competitive product markets in an emerging economy. The findings provide insightful information to regulators of other emerging countries that SOEs with good corporate governance practices can play an important role in the economy by mitigating the negative effect of higher PMC on firm performance.
Regulatory restriction on executive compensation, corporate governance and firm performance
Authors: Jiang Haiyan , Zhang Honghui
Published: November 2017

Purpose

The purpose of this paper is to investigate whether regulatory restriction on executive compensation in Chinese state-owned enterprises is beneficial to firm performance. The authors also examine the role of monitoring mechanisms in offsetting the effect of compensation restriction.

Design/methodology/approach

Multivariate analysis is conducted using archival data from Chinese listed companies over the period of 2007-2014.

Findings

The findings show that the restriction on executive compensation is negatively associated with a firm’s accounting performance, and this negative effect is ameliorated in firms with good internal control and a high level of institutional shareholding. Additional analysis reveals that the negative effect of pay restriction on firm performance is more pronounced in central government-controlled listed SOEs than in those controlled by local government.

Originality/value

This study is the first to investigate a government’s say-on-pay policy. Specifically, the findings pinpoint the inefficacy of regulatory intervention in corporate executive compensation. The findings add to compensation literature using China’s unique institutional setting.
A toolkit to examine multi-item measures – avoiding pitfalls and flaws
Authors: Svensson Göran
Published: November 2017

Purpose

The purpose of this paper is to describe a toolkit to examine the wording and sentence structure in each item of multi-item measures to avoid pitfalls and flaws in questionnaire surveys.

Design/methodology/approach

Based on hands-on scholarly experiences, the toolkit is designed to examine the wording and sentence structure of multi-item measures.

Findings

The results show a compilation of conceivable pitfalls and flaws in the items of multi-item measures.

Research limitations/implications

This research offers scholars insights to enhance the wording and sentence structure in research surveys.

Practical implications

The findings offer a practitioner-oriented hands-on approach to examine measures in business surveys.

Originality/value

This paper contributes to a foundation to avoid pitfalls and flaws in validity and reliability of multi-item measures.
Managing knowledge boundaries for open innovation – lessons from the automotive industry
Authors: Wilhelm Miriam , Dolfsma Wilfred
Published: November 2017

Purpose

The rising need to innovate and obtain knowledge from more distant knowledge sources calls for new innovation strategies and a better integration of other external actors who lie outside the traditional automotive supply chain. Such an open innovation strategy challenges organizational boundaries both on the firm and supply chain level, yet our understanding of the functioning of such boundaries and how they can be managed to allow for purposive knowledge flows is limited. The paper aims to discuss these issues.

Design/methodology/approach

In a longitudinal case study, the authors trace the development of the first open innovation network in the German automotive industry over a period of five years based on archival data, semi-structured interviews, and field observations.

Findings

While the automotive industry is advanced in collaborating with suppliers for innovation, routines for assessing and integrating ideas from sources outside the supply chain are still underdeveloped. The authors show which current knowledge boundaries pose obstacles for open innovation initiatives in this industry, and how they could be mediated through the involvement of gatekeepers.

Originality/value

The authors challenge and clarify the notion of the “permeability of organizational boundaries” in the open innovation literature and investigate the role of gatekeepers for open innovation.
How does uncertainty affect workplace accidents? Exploring the role of information sharing in manufacturing networks
Authors: Wiengarten Frank , Longoni Annachiara
Published: November 2017

Purpose

The purpose of this paper is to assess the influence of uncertainty on workplace accidents at the plant level. Furthermore, this study explores such relation in complex settings (i.e. manufacturing networks) and assesses whether or not information sharing in such environments can reduce the potentially negative impact of uncertainty on accidents.

Design/methodology/approach

To assess the relationships between uncertainty, accidents and information sharing the authors utilise cross-country survey data collected through the sixth iteration of the International Manufacturing Strategy Survey. The authors conceptualise workplace accidents through production time lost due to accidents. Furthermore, the authors conduct multiple regression analyses to test the hypotheses.

Findings

Results suggest that procurement, production, and demand uncertainties do indeed lead to an increase in workplace accidents at the plant level. Furthermore, the negative impact of uncertainty can be significantly reduced through information sharing.

Originality/value

This study represents a comprehensive attempt to simultaneously assess the impact of uncertainty on workplace accidents at the plant level and the possible moderating impact of information sharing.
A quality evaluation approach to disclosing third mission activities and intellectual capital in Italian universities
Authors: Di Berardino Daniela , Corsi Christian
Published: November 2017

Purpose

Using the quality evaluation approach, the purpose of this paper is to analyze the contribution of intellectual capital (IC) to the development of the third mission in Italian universities, defining the impact of these activities in the regional context. This research aims to verify if the mandatory reporting on quality discloses the contribution of IC to value creation, enhancing the universities’ awareness about IC management and third mission development.

Design/methodology/approach

The convergence between IC framework and quality evaluation approach is tested through an empirical research on a sample of 71 Italian universities funded by the government. Statistical analyses use data collected for the period 2004-2014 during the national assessment for research activity and third mission performance. The impact of third mission on the university ecosystem is verified using the indexes related to the territorial development rates.

Findings

This research found significant IC disclosure in the quality evaluation model and it highlights the possible integration between the IC measures and the quality evaluation indicators. The research findings show also a positive impact of third mission activities in the university ecosystem and the relevant role of structural capital and relational capital in the development of third mission. These findings encourage a collegial discussion in the university governance and among academics, stimulating a strategic behavior in the whole system

Research limitations/implications

The paper focuses the attention on research activity and third mission, considering the final results provided by an external stakeholder of university. Further research must include the role of teaching activity and the opinion of universities’ managers, researchers and administrative staff.

Originality/value

Following the neo-institutional sociology perspective, this research analyses for the first time the convergence between the solid experience of quality assessment and the immature IC culture in Italian universities. This analysis explores the value created by intangible activities in the university ecosystem, with a longitudinal perspective, contributing to the fourth stage of the IC literature.