bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible Notch1 acetylation tunes proliferative signalling in cardiomyocytes
Authors: Collesi Chiara , Felician Giulia , Secco Ilaria , Gutierrez Maria Ines , Martelletti Elisa , Ali Hashim , Zentilin Lorena , Myers Michael P , Giacca Mauro
Published: November 2017

Aims

The Notch signalling pathway regulates the balance between proliferation and differentiation in several tissues, including the heart. Our previous work has demonstrated that the proliferative potential of neonatal cardiomyocytes relies on Notch1 activity. A deep investigation on the biochemical regulation of the Notch signalling in cardiomyocytes is the focus of the current research.

Methods and results

We show that the Notch1 intracellular domain is acetylated in proliferating neonatal rat cardiomyocytes and that acetylation tightly controls the amplitude and duration of Notch signalling. We found that acetylation extends the half-life of the protein, and enhanced its transcriptional activity, therefore counteracting apoptosis and sustaining cardiomyocyte proliferation. Sirt1 acted as a negative modulator of Notch1 signalling; its overexpression in cardiomyocytes reverted Notch acetylation and dampened its stability. A constitutively acetylated fusion protein between Notch1 and the acetyltransferase domain of p300 promoted cardiomyocyte proliferation, which was remarkably sustained over time. Viral vector-mediated expression of this protein enhanced heart regeneration after apical resection in neonatal mice.

Conclusion

These results identify the reversible acetylation of Notch1 as a novel mechanism to modulate its signalling in the heart and tune the proliferative potential of cardiomyocytes.
Leisure centre entrance charges and physical activity participation in England
Authors: Ward F , Halliday E C , Barr B , Higgerson J , Holt V
Published: November 2017

Reducing or eliminating the cost to the public of using leisure facilities is one tool that local authorities have available to reduce inequalities in physical activity (PA). There is limited evidence about the effect of leisure entrance charges and their impact on participation. This study aimed to ascertain how facility pricing influenced the decisions people made about how to pay and what to pay for and how, in turn, these decisions impacted on participation for different groups. A total of 83 members of the public living in 4 local authorities in the North West of England were involved in focus groups or individual interviews. The results show that cost was a key factor which influenced PA participation in low income neighbourhoods. In practise, however, the majority of service users navigated the range of prices or payment options to find one that was suitable rather than simply reporting whether leisure was affordable or not. Whilst pre-paid options (e.g. direct debit memberships) encouraged participation, entrance charges incurred each time an individual participated had a negative impact on frequency but were a convenient way of paying for occasional use or for people who were unable to afford a pre-paid option. Free access also helped people who could not afford pre-paid membership to exercise regularly as well as incentivizing non-users to try activities. The research concluded that policies that include components of free access and offer more flexible payment options are most likely to contribute to reducing inequalities in PA.
Bass–Serre Trees of Amalgamated Free Product C*-algebras
Authors: Hasegawa Kei
Published: November 2017

For any reduced amalgamated free product C*-algebra (A, E) = (A1, E1) *D(A2, E2), we introduce and study a canonical ambient C*-algebra ΔT (A, E) of A which generalizes the crossed product arising from the canonical action of an amalgamated free product group on the compactification of the associated Bass–Serre tree. Using an explicit identification of ΔT (A, E) with a Cuntz–Pimsner algebra we prove two kinds of “amenability” results for ΔT (A, E); nuclearity and universality. As applications of our framework, we provide new conceptual, and simpler proofs of several known theorems on approximation properties, embeddability, and KK-theory for reduced amalgamated free product C*-algebras.
Finite Saturation for Unirational Varieties
Authors: Sofos Efthymios , Wang Yuchao
Published: November 2017

We import ideas from geometry to settle Sarnak’s saturation problem for a large class of algebraic varieties.
International Criminal Courts and the Right to Information
Authors: Kavran Olga
Published: November 2017

Transparency of criminal proceedings is enshrined in international human rights instruments and the statutes of international criminal courts and tribunals. It is one of the fundamental rights of the accused and also a right of the public to be informed about the work of international judicial institutions. This article considers the rights at issue and looks at how international courts have discharged their duty to provide information to those interested in their work. It discusses freedom of information and what it means to conduct public trials at the international level. It analyses the public’s right to know and how it should apply to international judicial institutions. The article provides concrete proposals for measures that could be adopted to ensure full compliance with the freedom of information guarantees.
The Neuroscience of Cognition and Cognitive Enhancing Compounds
Authors: Arnsten Amy F. T. , Wang Min J. , Paspalas Constantinos D.
Published: November 2017

Higher cognitive disorders involve insults to the neural circuits of the newly evolved association cortices. Although these cortices comprise the majority of the human cortex, little is understood about their molecular modulation. Research on the primate dorsolateral prefrontal cortex (dlPFC) indicates that the newly evolved layer III circuits underlying mental representation are regulated at the molecular level in a manner that is fundamentally different from classic synapses. These mechanisms must be respected to create effective treatments for human disorders, where a major goal is to optimize the network connectivity needed for persistent and precise neural representations. Understanding the needs of dlPFC circuits has led to the successful translation of guanfacine (Intuniv) for treating cognitive disorders, supporting this research strategy.
Cognitive Enhancers for Alzheimer’s Disease
Authors: Tsai Po-Heng
Published: November 2017

Alzheimer’s disease (AD) is the most common cause of dementia. In the United States, an estimated 5.3 million people had AD dementia in 2015, including 200,000 individuals younger than age 65 years. The number of people who are affected by AD is projected to reach 16 million in 2050. There is a tremendous cost associated with caring for people with AD. In 2015, the direct costs to US society of caring for those with AD totaled an estimated $226 billion, and if no effective disease-modifying treatments become available, this could increase to $1.1 trillion in 2050. In addition to medical costs, in 2014, caregivers of people with AD and other dementias provided an estimated 17.9 billion hours of unpaid assistance, which translates to a value of $217.7 billion. Therefore, cognitive enhancers for AD by improving cognition could address symptoms associated with AD, reduce caregiver burden, and limit health care costs.
Cognitive Enhancement in Major Depressive Disorder
Authors: Carvalho André F. , Alves Gilberto S. , Köhler Cristiano A. , McIntyre Roger S.
Published: November 2017

Major depressive disorder (MDD) is a chronic and disabling illness often associated with elevated rates of non-recovery and substantial psychosocial burden. Cognitive impairment is a common residual manifestations of MDD. Overactivation of the hypothalamic–pituitary–adrenal axis, along with immune–inflammatory imbalances, a decrease in neurotrophin signaling, and an increase in oxidative and nitrosative stress, leads to neuroprogression and cognitive deterioration in MDD. “Cognitive remission” has been proposed as a novel treatment target for MDD. Cognitive remediation therapy has provided encouraging results for the management of cognitive deficits in MDD. The effects of standard antidepressant drugs on MDD-related cognitive dysfunction are often suboptimal, which calls for the development of novel agents with the potential to target cognitive impairments in MDD. The incorporation of biobehavioral strategies (e.g., exercise) and multimodal treatment approaches (e.g., cognitive training, antidepressant therapy, and neuromodulation) is more likely to generate therapeutic benefit.
Autism, Attention Deficit Hyperactivity Disorder, and Cognitive Enhancement
Authors: Dud Iulia , Brennan Louise , Robertson Dene
Published: November 2017

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are common neurodevelopmental disorders. Impairments in attention and executive functions are core characteristics of ADHD. ASD is primarily characterized by severe deficits in social communication, but cognitive impairments are common, including in attention and executive functions. Currently, there is only limited evidence for efficacy of either pharmacological or behavioral interventions for the treatment of the cognitive deficits associated with the disorders. This chapter presents the current evidence base for cognitive enhancements for ADHD and ASD. It summarizes evidence from available and experimental pharmacological interventions, as well as behavioral, cognitive, and psychosocial interventions. The chapter also discusses the limitations of current tools and future directions.
Targeted Treatment for Cognitive Impairment Associated with Cancer and Cancer Treatment
Authors: Kesler Shelli R. , Wefel Jeffrey S.
Published: November 2017

Cognitive difficulty is one of the most common quality-of-life complaints among cancer patients and survivors. Cancer-related cognitive impairment (CRCI) is a common problem among cancer patients and survivors that extends disease-related morbidity; reduces quality of life; interferes with treatment adherence; and is a significant predictor of health behavior, disease progression, and survival. Several emerging management strategies for CRCI show promise for preventing and/or ameliorating CRCI. This chapter describes the incidence, symptoms, and putative mechanisms of CRCI and then discusses potential approaches for addressing CRCI. The focus of the interventions discussed in this chapter is on directions for future research that will potentially lead to widely accessible, effective, and ecologically valid approaches.
Ethical Considerations in Cognitive Enhancement
Authors: Arias Jalayne J. , Kibbe Bryan , Ford Paul J.
Published: November 2017

Cognitive enhancing modalities continue to be developed to target a variety of attributes, including memory, attention, reasoning, processing speed, and affect. The availability of cognitive enhancing modalities raises important ethical questions and considerations, particularly for the treating physicians. For example, is it ethically permissible or prohibited to prescribe a healthy patient a drug that would increase cognitive functioning? What arguments might justify the prescription or application of a cognitive enhancement for a patient? What arguments and considerations justify prohibiting cognitive enhancements or imposing various restrictions and guidelines for use? This chapter provides physicians with ethical resources needed to address these questions.
Regulatory Issues in Cognitive Enhancement Treatment Development
Authors: Kozauer Nicholas , Broich Karl
Published: November 2017

Improvement of cognition by medicinal products is an accepted concept by regulatory agencies. In dementing conditions such as Alzheimer’s disease, improvement of cognition or slowing its deterioration is essential for approval, particularly in early and mild to moderate stages of Alzheimer’s disease. In conditions such as schizophrenia or major depression, treatment of cognitive impairment is not considered as a pseudospecific indication, and specific clinical trials for such an indication are underway. Assessment tools for measurements of change in cognition and its relevance in functional or global outcome parameters must be validated in well-described patient populations. Developers are strongly encouraged to request scientific advice by regulatory agencies early in their programs to avoid delays or setbacks due to methodological or policy issues.
Neuroprotection for Spinal Cord Injury
Authors: Ahuja Christopher S. , Fehlings Michael
Published: November 2017

Traumatic spinal cord injuries (SCI) often have a devastating impact on quality of life for patients and their families. Neuroprotection for spinal cord injury is aimed at improving functional outcomes by limiting secondary injury processes that occur within the first minutes, hours, and days following the primary injury. The primary mechanical trauma initiates a secondary injury cascade where ischemia, inflammatory cell infiltration, and cytotoxic changes in the microenvironment cause further cell death and loss of function. Time-sensitive neuroprotective measures targeting these secondary insults have emerged as key therapeutic strategies. This chapter summarizes current evidence-based neuroprotective treatments, such as blood pressure augmentation, early surgical decompression, and intravenous methylprednisolone, as well as important emerging interventions, including therapeutic hypothermia, sodium channel blockade using riluzole, and the anti-inflammatory actions of minocycline. The chapter concludes by summarizing the current guidelines that all practitioners should be well-versed in prior to providing care for patients with SCI.
Neuroprotection for Spine Surgery
Authors: Brallier Jess W. , Gal Jonathan S.
Published: November 2017

Perioperative neurologic injury related to spine surgery, albeit rare, can result in devastating functional loss. As the number of spine operations has increased, so has the need for strategies designed to avoid and protect against such injury. This chapter reviews the common etiologies of neurologic deficits secondary to spine surgery and the factors that place patients at increased risk for developing these complications. The use of intraoperative neuromonitoring, including somatosensory evoked potentials (SSEPs), electromyography (EMG), and transcranial motor evoked potentials (TcMEPs), to detect surgical trespass of neuronal elements is also reviewed. The authors also summarize the role of physiologic parameter optimization, including mean arterial blood pressure and body temperature, and pharmacologic interventions, should an injury occur. Current practice guidelines for preventing and managing perioperative neurologic injury are described.
Fundamentals
Authors: Basu Sanjay
Published: November 2017

In this chapter, the author defines and provides examples of several key terms used in public health and healthcare modeling research. The chapter begins by clarifying the differences between key terms used to describe rates of disease (incidence, prevalence, and mortality) as well as the performance characteristics of tests used to detect disease (sensitivity, specificity, positive predictive value, and negative predictive value), prevent or treat disease (odds ratios, relative risks), understand studies (case-control, cohort, and randomized controlled trials), and avoid common study problems (bias, confounding). Understanding these key terms and how they are used in research studies allows the reader to correctly interpret study results.
Learning Disabilities in Mathematics
Authors: Franz Carleen , Ascherman Lee , Shaftel Julia
Published: November 2017

This chapter illustrates the complexity of the mathematics curriculum and why students who struggle to comprehend mathematics face additional challenges in terms of remedial instruction. Mathematics disabilities are more common than often believed. These difficulties frequently stem from a deficit in basic numeracy, or an understanding of how numbers work and how our number system operates. A breakdown of mathematics concept areas from the Common Core State Standards illustrates the breadth of mathematics content. Case studies exemplify various presentations of mathematics disorders. Mathematics problems may remain undercover longer than other types of disabilities, and identification of a mathematics learning disorder may not occur until college. Assessment and remedial techniques are included.
miR-16 Suppresses Growth of Rhabdoid Tumor Cells
Authors: Stroup Emily Kunce , Yeu Yunku , Budhipramono Albert , Hwang Tae Hyun , Rakheja Dinesh , Erdreich-Epstein Anat , Laetsch Theodore W. , Amatruda James F. , Chen Kenneth S.
Published: November 2017

Background

Rhabdoid tumor is a highly aggressive pediatric cancer characterized by biallelic loss and/or mutation of SMARCB1. Outcomes remain poor, and there are no established ways to target the tumorigenic pathways driven by SMARCB1 inactivation. SMARCB1 loss leads to an increase in cyclin D transcription.

Procedure

We characterized the cell line WT-CLS1, which has been described previously as Wilms tumor, by whole-exome sequencing, RNA-seq, and xenograft histology. We measured the effect of microRNA overexpression on WT-CLS1, BT-12, and CHLA-06-ATRT.

Results

We found that WT-CLS1 demonstrates the histological, mutational, and transcriptional hallmarks of rhabdoid tumor. Because the microRNAs let-7 and miR-16 can target cyclin D genes, we next overexpressed each of these microRNAs in WT-CLS1. We found that miR-16 reduced cell accumulation. This was accompanied by a decrease in proliferation markers and an increase in apoptosis markers. These results were replicated in the BT-12 and CHLA-06-ATRT cell lines.

Conclusions

The loss-of-function SMARCB1 mutation found in WT-CLS1, in conjunction with immunohistochemical and gene expression analysis, warrants reclassification of this cell line as rhabdoid tumor. Proliferation of WT-CLS1 and other rhabdoid tumor cell lines is significantly abrogated by miR-16 overexpression. Further studies are necessary to gain insight into the potential for miR-16 to be used as a novel therapeutic in rhabdoid tumor.

Abbreviations

(ATRT)

atypical teratoid/rhabdoid tumor

(miRNA)

microRNA

(dox)

doxycycline

(OD595)

optical density at 595 nm

(CDK4)

cyclin-dependent kinase 4
Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data
Authors: Finotello Francesca , Mayer Clemens , Plattner Christina , Laschober Gerhard , Rieder Dietmar , Hackl Hubert , Krogsdam Anne , Loncova Zuzana , Posch Wilfried , Wilflingseder Doris , Sopper Sieghart , Ijsselsteijn Marieke , Johnson Douglas , Xu Yaomin , Wang Yu , Sanders Melinda E. , Estrada Monica V. , Ericsson-Gonzalez Paula , Balko Justin , Miranda Noel de , Trajanoski Zlatko
Published: November 2017

The immune contexture has a prognostic value in several cancers and the study of its pharmacological modulation could identify drugs acting synergistically with immune checkpoint blockers. However, the quantification of the immune contexture is hampered by the lack of simple and efficient methods. We developed quanTIseq, a deconvolution method that quantifies the densities of ten immune cell types from bulk RNA sequencing data and tissue imaging data. We performed extensive validation using simulated data, flow cytometry data, and immunohistochemistry data from three cancer cohorts.

Analysis of 8,000 samples showed that the activation of the CXCR3/CXCL9 axis, rather than the mutational load is associated with cytotoxic T cell infiltration. We also show the prognostic value of deconvolution-based immunoscore and T cell/B cell score in several solid cancers. Finally, we used quanTIseq to show how kinase inhibitors modulate the immune contexture, and we suggest that it might have predictive value for immunotherapy.
New synthetic-diploid benchmark for accurate variant calling evaluation
Authors: Li Heng , Bloom Jonathan M , Farjoun Yossi , Fleharty Mark , Gauthier Laura , Neale Benjamin , MacArthur Daniel
Published: November 2017

Constructed from the consensus of multiple variant callers based on short-read data, existing benchmark datasets for evaluating variant calling accuracy are biased toward easy regions accessible by known algorithms. We derived a new benchmark dataset from the de novo PacBio assemblies of two human cell lines that are homozygous across the whole genome. This benchmark provides a more accurate and less biased estimate of the error rate of small variant calls in a realistic context.
Prediction of Acute Kidney Injury with a Machine Learning Algorithm using Electronic Health Record Data
Authors: Mohamadlou Hamid , Lynn-Palevsky Anna , Barton Christopher , Chettipally Uli , Shieh Lisa , Calvert Jacob , Das Ritankar
Published: November 2017

Background

A major problem in treating acute kidney injury (AKI) is that clinical criteria for recognition are markers of established kidney damage or impaired function; treatment before such damage manifests is desirable. Clinicians could intervene during what may be a crucial stage for preventing permanent kidney injury if patients with incipient AKI and those at high risk of developing AKI could be identified.

Methods

We used a machine learning technique, boosted ensembles of decision trees, to train an AKI prediction tool on retrospective data from inpatients at Stanford Medical Center and intensive care unit patients at Beth Israel Deaconess Medical Center. We tested the algorithm’s ability to detect AKI at onset, and to predict AKI 12, 24, 48, and 72 hours before onset, and compared its 3-fold cross-validation performance to the SOFA score for AKI identification in terms of Area Under the Receiver Operating Characteristic (AUROC).

Results

The prediction algorithm achieves AUROC of 0.872 (95% CI 0.867, 0.878) for AKI onset detection, superior to the SOFA score AUROC of 0.815 (P < 0.01). At 72 hours before onset, the algorithm achieves AUROC of 0.728 (95% CI 0.719, 0.737), compared to the SOFA score AUROC of 0.720 (P < 0.01).

Conclusions

The results of these experiments suggest that a machine-learning-based AKI prediction tool may offer important prognostic capabilities for determining which patients are likely to suffer AKI, potentially allowing clinicians to intervene before kidney damage manifests.
Skeletal muscle fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH-dependent regulation of adipogenesis
Authors: Marinkovic Milica , Sacco Francesca , Spada Filomena , Petrilli Lucia Lisa , Fuoco Claudia , Micarelli Elisa , Pavlidou Theodora , Castagnoli Luisa , Mann Matthias , Gargioli Cesare , Cesareni Gianni
Published: November 2017

Fibro adipogenic progenitors (FAPs) promote satellite cell differentiation in adult skeletal muscle regeneration. However, in pathological conditions, FAPs are responsible for fibrosis and fat infiltrations. Here we show that the NOTCH pathway negatively modulates FAP differentiation both in vitro and in vivo. However, FAPs isolated from young dystrophin-deficient mdx mice are insensitive to this control mechanism. Nonetheless, factors released by hematopoietic cells restore the sensitivity to NOTCH adipogenic inhibition. An unbiased mass spectrometry-based proteomic analysis of FAPs from muscles of wild type and mdx mice, revealed that the synergistic cooperation between NOTCH and inflammatory signals controls FAP differentiation. These results offer a basis for rationalizing the pathological outcomes of fat infiltrations in skeletal muscle and may suggest new therapeutic strategies to mitigate the detrimental effects of fatty depositions in muscles of dystrophic patients.

Highlights

Single-cell mass cytometry reveals that wt and mdx FAPs are in different cell states.

Activation of the NOTCH signaling pathway negatively regulates adipogenesis of wt but not mdx FAPs.

Deep proteomics suggests a mechanism explaining the different sensitivity of mdx- FAPs to NOTCH.

TNF-a stimulation restores the anti-adipogenic effect of NOTCH in mdx FAPs.
Phylogenetic analysis of West Nile Virus in Maricopa County, Arizona: Evidence for dynamic behavior of strains in two major lineages in the American Southwest
Authors: Hepp Crystal M. , Cocking Jill Hager , Valentine Michael , Young Steven J. , Damien Dan , Sheridan Krystal , Fofanov Viacheslav Y. , Busch Joseph D. , Erickson Daryn E. , Lancione Ryan C. , Smith Kirk , Will James , Townsend John , Keim Paul S. , Engelthaler David M.
Published: November 2017

West Nile Virus (WNV) has been detected annually in Maricopa County, Arizona, since 2003. With this in mind, we sought to determine if contemporary strains are established within the county or are annually imported. As part of this effort, we developed a new protocol for tiled amplicon sequencing of WNV to efficiently attain greater than 99% coverage of 14 WNV genomes collected directly from positive mosquito pools distributed throughout Maricopa County between 2014 and 2017. Bayesian phylogenetic analyses revealed that the contemporary genomes fall within two major lineages, NA/WN02 and SW/WN03. We found that all of the Arizona strains possessed a mutation known to be under positive selection (NS5-K314R), which has arisen independently four times. The SW/WN03 strains exhibited transient behavior, with at least 10 separate introductions into Arizona when considering both historical and contemporary strains. However, NA/WN02 strains are geographically differentiated and appear to be established in Arizona, with likely origins in New York. The clade of New York and Arizona strains looks to be the most ancestral extant lineage of WNV still circulating in the United States. The establishment of WNV strains in Maricopa County provides the first evidence of local overwintering by a WNV strain over the course of several years in Arizona.
Regulatory mechanisms are revealed by the distribution of transcription initiation times in single microbial cells
Authors: Choubey Sandeep , Kondev Jane , Sanchez Alvaro
Published: November 2017

Transcription is the dominant point of control of gene expression. Biochemical studies have revealed key molecular components of transcription and their interactions, but the dynamics of transcription initiation in cells is still poorly understood. This state of affairs is being remedied with experiments that observe transcriptional dynamics in single cells using fluorescent reporters. Quantitative information about transcription initiation dynamics can also be extracted from experiments that use electron micrographs of RNA polymerases caught in the act of transcribing a gene (Miller spreads). Inspired by these data we analyze a general stochastic model of transcription initiation and elongation, and compute the distribution of transcription initiation times. We show that different mechanisms of initiation leave distinct signatures in the distribution of initiation times that can be compared to experiments. We analyze published micrographs of RNA polymerases transcribing ribosomal RNA genes inE.coliand compare the observed distributions of inter-polymerase distances with the predictions from previously hypothesized mechanisms for the regulation of these genes. Our analysis demonstrates the potential of measuring the distribution of time intervals between initiation events as a probe for dissecting mechanisms of transcription initiation in live cells.
Fast voltage sensitivity in retinal pigment epithelium: sodium channels and their novel role in phagocytosis
Authors: Johansson Julia K. , Ihalainen Teemu O. , Skottman Heli , Nymark Soile
Published: November 2017

Despite the discoveries of voltage-gated sodium channels (Nav) from a number of non-excitable cell types, the presence of Nav-mediated currents in cells of the retinal pigment epithelium (RPE) has been dismissed as a cell culture artifact. Here, we challenge this notion by demonstrating functional Nav1.4-Nav1.6 and Nav1.8 channels in human embryonic stem cell derived and mouse RPE. Importantly, we show that Navs are involved in photoreceptor outer segment phagocytosis: blocking their activity significantly reduces the efficiency of this process. Consistent with this role, Nav1.8 co-localizes with the endosomal marker Rab7 and, during phagocytosis, with opsin. Nav1.4 localizes strongly to the cell-cell junctions together with the gap junction protein Connexin 43. During phagocytosis, both are localized to the phagosomes with a concurrent decrease in the junctional localization. Our study demonstrates that Navs give the capacity of fast electrical signaling to RPE and that Navs play a novel role in photoreceptor outer segment phagocytosis.
Quantifying relationships between chromosome organization and chromosomal aberrations
Authors: Eidelman Y.A. , Slanina S.V. , Andreev S.G.
Published: November 2017

The question of to what extent large scale structure of interphase chromosomes contributes to chromosomal exchange aberrations is discussed for a long time but still remains unclear. We designed the polymer model of 3D organization of a mouse chromosome and simulated X-ray induced chromosomal aberrations exploring two alternative hypotheses: the probability of contacted damaged loci entailing a chromosomal rearrangement is (a) a constant value or (b) not constant, depending on the distribution of DNAsel-hypersensitivity peaks along the chromosome. The latter hypothesis proved to explain the experimental data better than the former, meaning that not only large-scale structure but also local chromatin alterations play a role.
Cerebral Autoregulation, CSF outflow resistance and outcome following CSF diversion in Normal Pressure Hydrocephalus
Authors: Lalou Afroditi Despina , Czosnyka Marek , Donnelly Joseph , Pickard John D. , Nabbanja Eva , Keong. Nicole , Garnett Matthew , Czosnyka Zofia
Published: November 2017

Introduction

Normal pressure hydrocephalus (NPH) is not simply the result of a disturbance in cerebrospinal fluid (CSF) circulation, but often includes cardiovascular comorbidity and abnormalities within the cerebral mantle. In this study, we have examined the relationship between the global autoregulation pressure reactivity index (PRx), the profile of disturbed CSF circulation and pressure-volume compensation, and their possible effects on outcome after surgery.

Materials and methods

We studied a cohort of 131 patients, investigated for possible NPH. Parameters describing CSF compensation and circulation were calculated during the cerebrospinal fluid (CSF) infusion test and PRx was calculated from CSF pressure and arterial pressure recordings. A simple scale was used to mark the patients’ outcome 6 months after surgery (improvement, temporary improvement, and no improvement).

Results

PRx was negatively correlated with Rout (R=−0.18; p=0.044); patients with normal CSF circulation tended to have worse autoregulation. The correlation for patients who were surgically-managed (N=83) was: R=−0.28; p=0.03, and stronger in patients who improved after surgery (N=64; R=−0.36; p=0.03). In patients who did not improve, the correlation was not significantly different from zero (N= 19; R=0.17; p=0.15). There was a trend towards higher values for PRx in non-responders than in responders (PRx =0.16+/− 0.04 vs 0.09 +/−0.02 respectively; p=0.061), associated with higher MAP values (107.2+/−8.2 in non-responders vs 89.5+/−3.5 in responders; p=0.195). The product of MAP* (1+PRx), proposed as a measure of combined arterial hypertension and deranged autoregulation, showed a significant association with outcome (greater value in non-responders; p=0.013).

Conclusion

Autoregulation proves to associate with cerebrospinal fluid circulation, and appears strongest in shunt responders. Outcome following CSF diversion is possibly most favorable when CSF outflow resistance is increased and global cerebral autoregulation is intact, in combination with arterial normotension.
Nuclear Export Through Nuclear Envelope Remodeling inSaccharomyces cerevisiae
Authors: Ding Baojin , Mirza Anne M. , Ashley James , Budnik Vivian , Munson Mary
Published: November 2017

In eukaryotes, subsets of exported mRNAs are organized into large ribonucleoprotein (megaRNP) granules. How megaRNPs exit the nucleus is unclear, as their diameters are much larger than the nuclear pore complex (NPC) central channel. We previously identified a non-canonical nuclear export mechanism inDrosophila(Speese et al.,Cell2012) and mammals (Ding et al., in preparation), in which megaRNPs exit the nucleus by budding across nuclear envelope (NE) membranes. Here, we present evidence for a similar pathway in the nucleus of the budding yeast S.cerevisiae, which contain morphologically similar granules bearing mRNAs. Wild-type yeast displayed these granules at very low frequency, but this frequency was dramatically increased when the non-essential NPC protein Nup116 was deleted. These granules were not artifacts of defective NPCs; a mutation in the exportinXPO1(CRM1), in which NPCs are normal, induced similar megaRNP upregulation. We hypothesize that a non-canonical nuclear export pathway, analogous to those observed inDrosophilaand in mammalian cells, exists in yeast, and that this pathway is upregulated for use when NPCs or nuclear export are impaired.

Ding et al., describe a non-canonical mRNA export pathway in budding yeast similar to that observed inDrosophila. This pathway appears upregulated when the NPC is impaired, nuclear envelope integrity is disrupted, or the export factor Xpo1 (CRM1) is defective.
A novel PRRT2 pathogenic variant in a family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures
Authors: Lu Jacqueline G. , Bishop Juliet , Cheyette Sarah , Zhulin Igor B. , Guo Su , Sobreira Nara , Brenner Steven E.
Published: November 2017

Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder characterized by recurrent attacks of dyskinetic movements without alteration of consciousness that are often triggered by the initiation of voluntary movements. Whole-exome sequencing has revealed a cluster of pathogenic variants in PRRT2 (proline-rich transmembrane protein), a gene with a function in synaptic regulation that remains poorly understood. Here, we report the discovery of a novel PRRT2 pathogenic variant inherited in an autosomal dominant pattern in a family with PKD and benign familial infantile seizures (BFIS). After targeted Sanger sequencing did not identify the presence of previously described PRRT2 pathogenic variants, we carried out whole-exome sequencing in the proband and her affected paternal grandfather. This led to the discovery of a novel PRRT2 variant, NM_001256442:exon3:c.C959T/NP_660282.2:p.A320V, altering an evolutionarily conserved alanine at the amino acid position 320 located in the M2 transmembrane region. Sanger sequencing further confirmed the presence of this variant in four affected family members (paternal grandfather, father, brother, and proband) and its absence in two unaffected ones (paternal grandmother and mother). This newly found variant further reinforces the importance of PRRT2 in PKD, BFIS, and possibly other movement disorders. Future functional studies using animal models and human pluripotent stem cell models will provide new insights into the role of PRRT2 and the significance of this variant in regulating neural development and/or function.
Utilization PPP method in aircraft positioning in post-processing mode
Authors: Krasuski Kamil , Wierzbicki Damian , Jafernik Henryk
Published: November 2017

Purpose

The purpose of this paper is to study the implementation of GNSS technique in aviation for recovery of aircraft’s position using Precise Point Positioning (PPP) method.

Design/methodology/approach

The aircraft’s coordinates in ellipsoidal frame were obtained based on GPS code and phase observations for PPP method. The numerical computations were executed in post-processing mode in the CSRS-PPP and magicPPP online services. The mathematical scheme of PPP method was development using indifference equations of Ionosphere-Free linear combination. In the experiment, airborne test using Cessna 172 aircraft on June 01, 2010 in the military airport in Deblin was realized. The aircraft’s position was determined using data from GNSS receiver (Topcon HiperPro with interval of 1 s).

Findings

In this paper, the accuracy of aircraft’s position is better than 0.07 m for CSRS-PPP service and better than 0.27 m for magicPPP service. In case of the Mean Radial Spherical Error parameter, the average value for CSRS-PPP service equals to 0.01 m, whereas for magicPPP, it is about 0.38 m. The values of vertical coordinate of Cessna 172 aircraft were also checked with results of Real Time Kinematic–On The Fly technique.

Research limitations/implications

In this paper, the analysis of aircraft positioning is focused on the application of the PPP method in post-processing mode. In near real time, the PPP method still has limitations, especially in the area of ambiguity resolution and also instrumental biases (e.g. Narrow Lane Hardware Delays).

Practical implications

The PPP method can be applied in aviation in post-processing mode for verification of true aircraft coordinates and elimination of blunder errors from adjustment processing of GNSS observations. The Zenith Wet Delay term as a product of troposphere delay and receiver clock bias as a product of precise time transfer can be obtained in the PPP method.

Originality/value

The paper presents that the PPP method is an alternative solution for the recovery of aircraft’s position in aviation, and this method can be also applied in the positioning of aircraft based on GLONASS or GPS/GLONASS data.
Aircraft test of engineered material arresting system
Authors: Yao Hong-Yu , Kong Xiang-Jun , Shi Ya-Jie , Xiao Xian-Bo , Le Ning-Ning
Published: November 2017

Purpose

Engineered material arresting systems (EMASs) are dedicated to stopping aircraft that overrun the runway before they enter dangerous terrain. The system consists of low-strength foamed concretes. The core component of the arresting system design is a reliable simulation model. Aircraft test verification is required before the practical application of the model. This study aims to propose a simulation model for the arresting system design and conducts serial verification tests.

Design/methodology/approach

Six verification tests were conducted using a Boeing 737 aircraft. The aircraft was equipped with an extra inertia navigation system and a strain gauge system to measure its motion and the forces exerted on the landing gears. The heights of the arrestor beds for these tests were either 240 or 310 mm, and the entering speeds of the aircraft ranged from 23.9 to 60.6 knots.

Findings

Test results revealed that both the aircraft and the pilots on board were safe after the tests. The maximum transient acceleration experienced by the dummies on board was 2.5 g, which is within the human tolerance. The model exhibited a satisfied accuracy to the field tests, as the calculation errors of the stopping distances were no greater than 7 per cent.

Originality/value

This study proposes a simulation model for the arresting system design and conducts serial verification tests. The model can be used in EMAS design.
Aircraft wing design at low speeds using Taguchi method
Authors: Soylak Mustafa , Karagöz Gökçe Nurseda , Topal Eyüp Sabri
Published: November 2017

Purpose

The purpose of this paper is to determine the impact level of parameters affecting wing design at low speeds using Taguchi method.

Design/methodology/approach

Using brain storming approach airfoil shape, wing angle of attack and Reynolds number are determined as important wing design parameters. Most important parameters over these parameters are determined using Taguchi method. The lift-to-drag ratio (CL/CD ratio) is chosen as the performance criterion and L8 orthogonal index is chosen as experimental study scheme for this study.

Findings

Experimental results are examined using Taguchi method. After making experiments and also analyses, Reynolds number is found as the most important and identifier parameter for aircraft wing design.

Practical implications

Taguchi method makes the experimental design for experimental studies. This method reduces the number of experiments substantially using orthogonal indices while keeping effects of uncontrolled parameters to a minimum. Reduction in number of experiments helps save time and also cost.

Originality/value

In this study, with less number of experiments, the most important parameter for aircraft wing design is determined. Moreover, with less number of experiments, not only is time saved but the design stage is also made faster.
Comparison of 1D and 3D thermal models of the nacelle ventilation system in a small airplane
Authors: Łapka Piotr , Bakker Marije , Furmański Piotr , van Tongeren Hans
Published: November 2017

Purpose

Insight in the temperature distribution on the internal and external surface of the nacelle is of great importance during the design phase of an aircraft. However, detailed information is not always needed. In a preliminary project stage or during parametric optimization, short analysis times are often more crucial than high accuracy. In such cases, the global insight in the temperature levels suffices to gain understanding of the relevance and influence of certain parameters. Nevertheless, estimating the maximum temperature for the most adverse conditions should also be done before a prototype is built. Therefore, this study aims to present and compare a simplified and an advanced methodology for the analysis of engine bay cooling and ventilation systems as well as heat transfer in the nacelle in a small airplane equipped with a turboprop engine in the tractor arrangement.

Design/methodology/approach

Both approaches included conductive, convective and radiative heat transfer in the engine bay of the small airplane I-23 as well as heat conduction in the nacelle made of material with anisotropic thermal conductivity. The one-dimensional (1D) model assumed that the nacelle with the air flow and engine was represented by a lumped thermal model in which heat was exchanged between the different lumped segments (the nodes) and the flowing air and engine. The three-dimensional (3D) model was based on the continuous control volume approach for heat, fluid flow and thermal radiation as well as on realizable k-ε turbulence model. Both models used commercial software.

Findings

The temperature distribution at the internal and external surface of the top nacelle was calculated. The 1D model predicted a temperature per node (per segment) while the 3D model was able to determine its values accurately and find the location of hot spots. Considering the complex geometry of the engine bay and nacelle and the assumed simplification, the obtained 1D and 3D results agreed quite well.

Practical implications

Both models will help in the development of new ventilation and cooling systems of the engine bay and nacelle as well as in the selection of materials for parts of the top cowling in the newly redesigned airplane I-23 equipped with a turboprop engine. In addition, the methodology presented in this paper might be applied in the development of other airplanes.

Originality/value

The 1D and 3D models of complex heat transfer inside the engine bay and in the nacelle of the newly re-designed airplane I-23 were elaborated and compared.
Thermoelastic flexural analysis of FG-CNT doubly curved shell panel
Authors: Mehar Kulmani , Panda Subrata Kumar
Published: November 2017

Purpose

The purpose of this paper is to develop a general mathematical model for the evaluation of the theoretical flexural responses of the functionally graded carbon nanotube-reinforced composite doubly curved shell panel using higher-order shear deformation theory with thermal load. It is well-known that functionally graded materials are a multidimensional problem, and the present numerical model is also capable of solving the flexural behaviour of different shell panel made up of carbon nanotube-reinforced composite with adequate accuracy in the absence of experimentation.

Design/methodology/approach

In this current paper, the responses of the single-walled carbon nanotube-reinforced composite panel is computed numerically using the proposed generalised higher-order mathematical model through a homemade computer code developed in MATLAB. The desired flexural responses are computed numerically using the variational method.

Findings

The validity and the convergence behaviour of the present higher-order model indicate the necessity for the analysis of multidimensional structure under the combined loading condition. The effect of various design parameters on the flexural behaviour of functionally graded carbon nanotube doubly curved shell panel are examined to highlight the applicability of the presently proposed higher-order model under thermal environment.

Originality/value

In this paper, for the first time, the static behaviour of functionally graded carbon nanotube-reinforced composite doubly curved shell panel is analysed using higher-order shear deformation theory. The properties of carbon nanotube and the matrix material are considered to be temperature dependent. The present model is so general that it is capable of solving various geometries from single curve to doubly curved panel, including the flat panel.
A study of the relationships among environmental performance, environmental disclosure, and financial performance
Authors: Lu Lucy Wenxiang , Taylor Martin Edward
Published: November 2017

Purpose

The purpose of this paper is to study the relationships among environmental performance (EP), environmental disclosure (ED), and financial performance (FP) (three corporate constructs) using data from Newsweek’s green rankings.

Design/methodology/approach

Previous studies document mixed results about the relations among the three constructs. A firm’s overall management strategy may affect the three constructs simultaneously; therefore, the interrelationships among EP, ED, and FP were jointly examined. A simultaneous equations approach was used to test the hypothesis.

Findings

The three-stage least square (3SLS) estimation results show a negative relationship between EP and FP and a positive relationship between EP and ED, suggesting that financially successful firms are less likely good environmental performers but green firms are more likely to disclose their EP.

Research limitations/implications

Since the sample firms examined in this study are US large-size companies, the results found in this paper may not apply to small- and/or medium-size firms or to companies in other countries.

Practical implications

Three corporate constructs are jointly correlated with each one. A firm’s overall strategic plan on environmental engagement is likely reflected in how it engages in each of the constructs that affect costs and benefits. Sustainable efforts, in short term, may put firms at risk. Companies may need to take a long-term perspective when cutting costs is curtailed.

Originality/value

The research contributes to the ED and EP literature by using a 3SLS simultaneous equation method and analyzing a more recent and comprehensive multi-industry data. By controlling industry effect, the research investigates the interrelationships among three corporate constructs and finds interesting results. An interpretation and discussion are provided.