bluuebunny/crossref_metadata_2025 huggingface dataset:
Pardon the interruption: saccadic inhibition enables the rapid deployment of alternate oculomotor plans
Authors: Salinas Emilio , Stanford Terrence R.
Published: March 2018

Diverse psychophysical and neurophysiological results show that oculomotor networks are continuously active, such that plans for making the next eye movement are always ongoing. So, when new visual information arrives unexpectedly, how are those plans affected? At what point can the new information start guiding an eye movement, and how? Here, based on modeling and simulation results, we make two observations that are relevant to these questions. First, we note that many experiments, including those investigating the phenomenon known as “saccadic inhibition,” are consistent with the idea that sudden-onset stimuli briefly interrupt the gradual rise in neural activity associated with the preparation of an impending saccade. And second, we show that this stimulus-driven interruption is functionally adaptive, but only if perception is fast. In that case, putting on hold an ongoing saccade plan toward location A allows the oculomotor system to initiate a concurrent, alternative plan toward location B (where a stimulus just appeared), deliberate (briefly) on the priority of each target, and determine which plan should continue. Based on physiological data, we estimate that the actual advantage of this strategy, relative to one in which any plan once initiated must be completed, is of several tens of milliseconds.
Retinal Ganglion Cell Axon Sorting at the Optic Chiasm Requires Dystroglycan
Authors: Clements Reena , Wright Kevin M.
Published: March 2018

In the developing visual system, retinal ganglion cell (RGC) axons project from the retina to several distal retinorecipient regions in the brain. Several molecules have been implicated in guiding RGC axons in vivo, but the role of extracellular matrix molecules in this process remains poorly understood. Dystroglycan is a laminin-binding transmembrane protein important for formation and maintenance of the extracellular matrix and basement membranes and has previously been implicated in axon guidance in the developing spinal cord. Using two genetic models of functional dystroglycan loss, we show that dystroglycan is necessary for correct sorting of contralateral and ipsilateral RGC axons at the optic chiasm. Missorted axons still target retinorecipient brain regions and persist in adult mice, even after axon pruning is complete. Our results highlight the importance of the extracellular matrix for axon sorting at an intermediate choice point in the developing visual circuit.

Summary Statement

Abnormal retinal ganglion cell axon sorting in the optic chiasm in the absence of functional dystroglycan results in profound defects in retinorecipient innervation.
A statistical framework for cross-tissue transcriptome-wide association analysis
Authors: Hu Yiming , Li Mo , Lu Qiongshi , Weng Haoyi , Wang Jiawei , Zekavat Seyedeh M. , Yu Zhaolong , Li Boyang , Muchnik Sydney , Shi Yu , Kunkle Brian W. , Mukherjee Shubhabrata , Natarajan Pradeep , Naj Adam , Kuzma Amanda , Zhao Yi , Crane Paul K. ,   Alzheimer’s Disease Genetics Consortium, Zhao Hongyu
Published: March 2018

Transcriptome-wide association analysis is a powerful approach to studying the genetic architecture of complex traits. A key component of this approach is to build a model to predict (impute) gene expression levels from genotypes from samples with matched genotypes and expression levels in a specific tissue. However, it is challenging to develop robust and accurate imputation models with limited sample sizes for any single tissue. Here, we first introduce a multi-task learning approach to jointly impute gene expression in 44 human tissues. Compared with single-tissue methods, our approach achieved an average 39% improvement in imputation accuracy and generated effective imputation models for an average 120% (range 13%-339%) more genes in each tissue. We then describe a summary statistic-based testing framework that combines multiple single-tissue associations into a single powerful metric to quantify overall gene-trait association at the organism level. When our method, called UTMOST, was applied to analyze genome wide association results for 50 complex traits (Ntotal=4.5 million), we were able to identify considerably more genes in tissues enriched for trait heritability, and cross-tissue analysis significantly outperformed single-tissue strategies (p=1.7e-8). Finally, we performed a cross-tissue genome-wide association study for late-onset Alzheimer’s disease (LOAD) and replicated our findings in two independent datasets (Ntotal=175,776). In total, we identified 69 significant genes, many of which are novel, leading to novel insights on LOAD etiologies.
Microdeletions excludingYWHAEandPAFAH1B1cause a unique leukoencephalopathy and hypermobility syndrome: Further delineation of the 17p13.3 microdeletion spectrum
Authors: Emrick Lisa T. , Rosenfeld Jill A. , Lalani Seema R. , Jain Mahim , Hunter Jill V. , Nagakura Honey , Immken LaDonna L. , Burrage Lindsay C. , Bacino Carlos A. , Belmont John W. , Lee Brendan
Published: March 2018

Purpose

Brain malformations are caused by 17p13.3 deletions: lissencephaly with deletions of the larger Miller-Dieker syndrome region or smaller deletions of onlyPAFAH1B1, as well as various abnormalities, including white matter changes, in the distinct syndrome due to deletions includingYWHAEandCRKbut sparingPAFAH1B1.We sought to understand the significance of 17p13.3 deletions between theYWHAE/CRKandPAFAH1B1loci.

Methods

We analyzed the clinical features of five individuals from four families with 17p13.3 deletions between and not includingYWHAE/CRKandPAFAH1B1identified among individuals undergoing clinical chromosomal microarray testing.

Results

Four individuals from three families have multi-focal white matter lesions and hypermobile joints, while a fifth had a normal MRI. A combination of our patients and a review of those in the literature with white matter changes and deletions in this chromosomal region narrows the overlapping region for this brain phenotype to ∼345 kb, including 11 RefSeq genes, withRTN4RL1haploinsufficiency as the best candidate for causing this.

Conclusion

While previous literature has hypothesized dysmorphic features and white matter changes related toYWHAE, our cohort contributes evidence to the presence of additional genes within 17p13.3 required for proper brain development.
Linear motor driven-rotary motion of a membrane-permeabilized ghost in Mycoplasma mobile
Authors: Kinosita Yoshiaki , Miyata Makoto , Nishizaka Takayuki
Published: March 2018

Mycoplasma mobile exhibits a smooth gliding movement as does its membrane-permeabilized ghost model. This exceptionally prominent experimental system has allowed us to conclude that the energy source for M. mobile motility is adenosine triphosphate (ATP), and the gliding is largely comprised of repetitions of unitary steps of about 70 nm. In the present study, we show a new motility mode, in which the ghost model prepared with a high concentration of detergent exhibits directed rotational motions with a constant speed. With a rotational speed and viscous friction of a single ghost, the torque was estimated to be ∼30 pN nm at saturated [ATP]s. Although the origin of the rotation has not been conclusively settled, we found that rotary ghosts treated with sialyllactose, the binding target for leg proteins, were stopped. This result suggested that biomolecules embedded on the cell membrane nonspecifically attaches to the glass and works as a flexible pivot point, and the linear motion of the leg is a driving force for a rotary motion. This simple geometry exemplifies the new mechanism, by which the movement of a linear motor is efficiently converted to a constant rotation of the object on a micrometer scale.
Dynamics of human protein kinases linked to drug selectivity
Authors: Pitsawong Warintra , Buosi Vanessa , Otten Renee , Agafonov Roman V. , Zorba Adelajda , Kern Nadja , Kutter Steffen , Kern Gunther , Pádua Ricardo A. P. , Meniche Xavier , Kern Dorothee
Published: March 2018

Protein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinases Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase Aurora A. Using a combination of biophysical techniques, we propose a universal drug-binding mechanism, that rationalizes selectivity, affinity and long on-target residence time for kinase inhibitors. These new concepts, where protein dynamics in the drug-bound state plays the crucial role, can be applied to inhibitor design of targets outside the kinome.

eLife digest

The Ser/Thr kinase Aurora A is an important target for the development of new anticancer therapies. A longstanding question is how to specifically and effectively inhibit only this kinase in a background of over 550 protein kinases with very similar structures. To this end, understanding the inhibition mechanism of Aurora A by different drugs is essential. Here, we characterize the kinetic mechanism of three distinct kinase drugs, Gleevec (Imatinib), Danusertib (PHA739358) and AT9283 (Pyrazol-4-yl Urea) for Aurora A. We show that inhibitor affinities do not rely exclusively on the recognition of a specific conformation of the Asp-Phe-Gly loop of the kinase. Our quantitative kinetics data put forward an opposing mechanism in which a slow conformational change after drug binding (i.e., induced-fit step) dictates drug affinity.
MUTE Directly Orchestrates Cell State Switch and the Single Symmetric Division to Create Stomata
Authors: Han Soon-Ki , Qi Xingyun , Sugihara Kei , Dang Jonathan H. , Endo Takaho A. , Miller Kristen L. , Kim Eun-deok , Miura Takashi , Torii Keiko U.
Published: March 2018

Precise cell division control is critical for developmental patterning. For the differentiation of a functional stoma, a cellular valve for efficient gas exchange, the single symmetric division of an immediate precursor is absolutely essential. Yet, the mechanism governing the single division event remains unclear. Here we report the complete inventories of gene expression by the Arabidopsis bHLH protein MUTE, a potent inducer of stomatal differentiation. MUTE switches the gene expression program initiated by its sister bHLH, SPEECHLESS. MUTE directly induces a suite of cell-cycle genes, including CYCD5;1, and their transcriptional repressors, FAMA and FOUR LIPS. The architecture of the regulatory network initiated by MUTE represents an Incoherent Type 1 Feed-Forward Loop. Our mathematical modeling and experimental perturbations support a notion that MUTE orchestrates a transcriptional cascade leading to the tightly-restricted, robust pulse of cell-cycle gene expression, thereby ensuring the single cell division to create functional stomata.

Highlights

Complete inventories of gene expression in stomatal differentiation state are elucidated

MUTE switches stomatal patterning program initiated by its sister bHLH, SPEECHLESS

MUTE directly induces cell-cycle genes and their direct transcriptional repressors

Incoherent feed-forward loop by MUTE ensures the single division of a stomatal precursor
Open Force Field Consortium: Escaping atom types using direct chemical perception with SMIRNOFF v0.1
Authors: Mobley David L. , Bannan Caitlin C. , Rizzi Andrea , Bayly Christopher I. , Chodera John D. , Lim Victoria T. , Lim Nathan M. , Beauchamp Kyle. A. , Shirts Michael R. , Gilson Michael K. , Eastman Peter K.
Published: March 2018

Here, we focus on testing and improving force fields for molecular modeling, which see widespread use in diverse areas of computational chemistry and biomolecular simulation. A key issue affecting the accuracy and transferrability of these force fields is the use of atom typing. Traditional approaches to defining molecular mechanics force fields must encode, within a discrete set of atom types, all information which will ever be needed about the chemical environment; parameters are then assigned by looking up combinations of these atom types in tables. This atom typing approach leads to a wide variety of problems such as inextensible atom-typing machinery, enormous difficulty in expanding parameters encoded by atom types, and unnecessarily proliferation of encoded parameters. Here, we describe a new approach to assigning parameters for molecular mechanics force fields based on the industry standard SMARTS chemical perception language (with extensions to identify specific atoms available in SMIRKS). In this approach, each force field term (bonds, angles, and torsions, and nonbonded interactions) features separate definitions assigned in a hierarchical manner without using atom types. We accomplish this using direct chemical perception, where parameters are assigned directly based on substructure queries operating on the molecule(s) being parameterized, thereby avoiding the intermediate step of assigning atom types — a step which can be considered indirect chemical perception. Direct chemical perception allows for substantial simplification of force fields, as well as additional generality in the substructure queries. This approach is applicable to a wide variety of (bio)molecular systems, and can greatly reduce the number of parameters needed to create a complete force field. Further flexibility can also be gained by allowing force field terms to be interpolated based on the assignment of fractional bond orders via the same procedure used to assign partial charges. As an example of the utility of this approach, we provide a minimalist small molecule force field derived from Merck’s parm@Frosst (an Amber parm99 descendant), in which a parameter definition file only ≈ 300 lines long can parameterize a large and diverse spectrum of pharmaceutically relevant small molecule chemical space. We benchmark this minimalist force field on the FreeSolv small molecule hydration free energy set and calculations of densities and dielectric constants from the ThermoML Archive, demonstrating that it achieves comparable accuracy to the Generalized Amber Force Field (GAFF) that consists of many thousands of parameters.
Genome-wide determinants of sequence-specific DNA binding of general regulatory factors
Authors: Rossi Matthew J. , Lai William K.M. , Pugh B. Franklin
Published: March 2018

General regulatory factors (GRFs), such as Reb1, Abf1, Rap1, Mcm1, and Cbf1, positionally organize yeast chromatin through interactions with a core consensus DNA sequence. It is assumed that sequence recognition via direct base readout suffices for specificity and that spurious nonfunctional sites are rendered inaccessible by chromatin. We tested these assumptions through genome-wide mapping of GRFs in vivo and in purified biochemical systems at near–base pair (bp) resolution using several ChIP-exo–based assays. We find that computationally predicted DNA shape features (e.g., minor groove width, helix twist, base roll, and propeller twist) that are not defined by a unique consensus sequence are embedded in the nonunique portions of GRF motifs and contribute critically to sequence-specific binding. This dual source specificity occurs at GRF sites in promoter regions where chromatin organization starts. Outside of promoter regions, strong consensus sites lack the shape component and consequently lack an intrinsic ability to bind cognate GRFs, without regard to influences from chromatin. However, sites having a weak consensus and low intrinsic affinity do exist in these regions but are rendered inaccessible in a chromatin environment. Thus, GRF site-specificity is achieved through integration of favorable DNA sequence and shape readouts in promoter regions and by chromatin-based exclusion from fortuitous weak sites within gene bodies. This study further revealed a severe G/C nucleotide cross-linking selectivity inherent in all formaldehyde-based ChIP assays, which includes ChIP-seq. However, for most tested proteins, G/C selectivity did not appreciably affect binding site detection, although it does place limits on the quantitativeness of occupancy levels.
Anomalous grazing-incidence small-angle X-ray scattering of Ga2O3-based nanoparticles
Authors: Revenant Christine
Published: March 2018

Grazing-incidence small-angle X-ray scattering (GISAXS) performed at several X-ray energies in the vicinity of the absorption edge of a considered element is called anomalous GISAXS (AGISAXS). This emerging technique takes advantage of the variation of the scattering factor near an absorption edge, allowing the morphology of multi-component nanomaterials to be unraveled. The selected model system for AGISAXS simulations is mainly an In2O3 layer containing Ga2O3-based nanoparticles. The transmission coefficients at the different X-ray energies near the Ga K edge are identical at one specific incident angle (near the critical angle). Hence, it could be relevant to perform AGISAXS at this incident angle in order to cancel the transmission modification as the X-ray energy changes. For buried nanoparticles, grazing-incidence effects are negligible with respect to the anomalous element-specific contribution provided that the experiments are performed at energies a few electronvolts below the absorption edge. Interestingly, AGISAXS has a clearly different intensity behavior versus X-ray energy for an embedded monodisperse spherical particle, a hole and a core–shell particle. Hence, AGISAXS can be used to unambiguously distinguish such embedded particles. Moreover, even for a dense layer of core–shell nanoparticles on a substrate, anomalous effects are much larger than grazing effects as the X-ray energy changes. Finally, it is shown that experimental anomalous scattering can be significant and can be satisfactorily simulated.
Developing high performance working through case study evidence
Authors: Grant Kirsteen , Maxwell Gillian A.
Published: March 2018

Purpose

This paper aims to theoretically proffer and empirically evidence five inter-related high performance working (HPW) groupings of value to practitioners interested in developing HPW in their organizations.

Design/methodology/approach

The empirical research is based on three UK-based qualitative case studies. Data are drawn from nine in-depth interviews with managers (three from each case) and three subsequent focus groups (one in each case). Focus groups comprised six, eight, and four employee (non-manager) interviewees.

Findings

The empirical findings validate the theoretical importance of the five identified HPW groupings. More, they imply a number of relationships within and between the five groupings, confirming the need to view the groupings collectively and dynamically.

Originality/value

The five HPW groupings provide a foundation for further research to closely evaluate the dynamism within and across the groupings. They also offer practical types of human resource interventions and actions for practitioners to evaluate the strengths and weaknesses of HPW in their organizations.
Municipal reaction to functional rescaling in Italy
Authors: Bolgherini Silvia , Casula Mattia , Marotta Mariano
Published: March 2018

Purpose

The purpose of this paper is to discuss the municipal reaction to a recent rescaling policy in Italy that, since 2010, require to small municipalities to jointly manage their basic tasks (compulsory joint management – CJM) through intermunicipal forms of cooperation. The paper will investigate: how many small municipalities did effectively join their basic tasks; which forms of cooperation did they choose to perform these tasks; and which kind of reaction municipalities enacted toward the national provision.

Design/methodology/approach

Quantitative data rely on an original database collecting information on all Italian municipalities up to 2015. A qualitative research has also been conducted by submitting a semi-structured questionnaire and interviews to the civil servants in charge of the CJM in each of the 20 Italian regions and to other privileged interlocutors.

Findings

Italian municipalities poorly complied with the CJM norm and when they did, they choose the easiest way to do it (using the simplest available intermunicipal cooperation form). Among the explanations for this reaction: the lack of consistency and clear political will of the national policy maker in respect to this norm and the lack of a mind set at the local level oriented to cooperation and networking.

Originality/value

This paper highlights the main patterns of conflict in functional rescaling of small-sized municipalities in Italy, thus providing both fresh new data on this phenomena and useful elements for shaping future policy making on this topic.
Can land value uplift deliver affordable housing? Experiences from England
Authors: Wyatt Peter
Published: March 2018

Purpose

The theoretical case for land value capture is well-known, but the effectiveness of affordable housing delivery as a capture mechanism is not so well-documented. Building on the earlier theoretical and empirical work of Whitehead (1991, 2007) and Crook and Whitehead (2002), the purpose of this paper is to consider the provision of affordable housing from a land value capture viewpoint, focusing on the process by which the amount of affordable housing is determined between landowners/developers on the one hand and local planning authorities on the other.

Design/methodology/approach

The paper adopts a mixed-mode approach for the data collection. Two surveys of local planning authorities were undertaken, together with a series of case study interviews.

Findings

The paper evaluates whether land value capture has been an effective mechanism for delivering affordable housing by focusing on three principal areas: first, the political agenda in relation to land value capture and the supply of affordable housing; second, the nature and motivation of the stakeholders involved in affordable housing decision-making; and third, the use of economic models as decision tools for determining the amount and type of affordable housing are negotiated.

Originality/value

The research provides some insight into the effectiveness of local authority affordable housing targets as a means of capturing the uplift in land value that results from the grant of planning permission.
The significance and performance of property companies on the AIM stock market
Authors: Newell Graeme , Marzuki Muhammad Jufri Bin
Published: March 2018

Purpose

The Alternative Investment Market (AIM) is an important UK growth-focused stock market. The purpose of this paper is to assess the significance, risk-adjusted performance and portfolio diversification benefits of property companies on the AIM stock market over 2005-2015. The post-Global Financial Crisis (GFC) recovery of property companies on AIM is highlighted, as well as their performance compared with property companies on the London Stock Exchange (LSE) main board.

Design/methodology/approach

Using monthly total returns, the risk-adjusted performance and portfolio diversification benefits of property companies on the AIM stock market over 2005-2015 are assessed and compared with a range of other asset classes. Sub-period analysis is used to assess the post-GFC recovery of the property companies on AIM.

Findings

Property companies on AIM delivered poor risk-adjusted returns over 2005-2015, with limited portfolio diversification benefits with the overall AIM stock market. However, since the GFC, property companies on AIM have delivered strong risk-adjusted returns, with improved portfolio diversification benefits with the overall AIM stock market. This post-GFC performance is shown to be more than a small cap effect, reflecting the property portfolios in these AIM property companies. Despite this strong post-GFC performance, the AIM property companies under-performed property companies on the LSE main board on a risk-adjusted basis.

Practical implications

AIM provides an important platform for property companies seeking start-up and growth opportunities in a less-regulated funding environment. This has been reinforced by strong risk-adjusted performance in a post-GFC context. However, the stronger risk-adjusted performance of LSE listed property companies and their superior scale, resources and higher quality property portfolios present challenges for increased investor support for the AIM property companies going forward.

Originality/value

This paper is the first published empirical research analysis of the risk-adjusted performance and diversification benefits of property companies on the AIM stock market. This research enables empirically validated, more informed and practical property investment decision-making regarding the strategic role of property companies on the AIM stock market in a portfolio.
Hong Kong Securities and Futures Commission (SFC) highlights operating, control and compliance deficiencies in asset management industry
Authors: Godfrey Anne-Marie
Published: March 2018

Purpose

To examine the nine common areas of non-compliance in managing investment funds and discretionary accounts, detailed in a Hong Kong Securities and Futures Commission (SFC) circular dated September 15, 2017, directed at SFC-licensed asset managers.

Design/methodology/approach

Discusses a July 2017 circular indicating the SFC’s general concerns and analyzing the following nine common areas of non-compliance cited in the September 15, 2017 circular: (1) inappropriate receipt of cash rebates giving rise to apparent conflicts of interests, (2) failure to follow investment-suitability and discretionary account mandates during solicitation, (3) failure to implement liquidity-risk management processes, (4) deficiencies in governance structures and fair-valuation procedures, (5) deficiencies in systems for ensuring best execution, (6) failure to safeguard fair order allocation, (7) inadequate controls for protection of client assets, (8) inadequate systems to comply with investment restrictions, and (9) inadequate safeguards to address market misconduct risk.

Findings

The nine examples of non-compliance provide a useful insight into key “problem areas” indicated to currently be of particular concern to the SFC.

Practical implications

All SFC-licensed asset managers would be well advised to revisit their internal governance structures and operational policies and procedures in order to ensure that they are compliant with applicable standards and requirements.

Originality/value

Practical guidance from a lawyer with extensive experience advising investment managers and advisers, fund administrators, trustees and other fund service providers on investment fund-related issues.
Abiotic and biotic interactions in the diffusive boundary layer of kelp blades create a potential refuge from ocean acidification
Authors: Noisette Fanny , Hurd Catriona
Published: March 2018

Seaweeds are able to modify the chemical environment at their surface, in a micro‐zone called the diffusive boundary layer (DBL), via their metabolic processes controlled by light intensity. Depending on the thickness of the DBL, sessile invertebrates such as calcifying bryozoans or tube‐forming polychaetes living on the surface of the blades can be affected by the chemical variations occurring in this microlayer. Especially in the context of ocean acidification (OA), these microhabitats might be considered as a refuge from lower pH, because during the day photosynthesis temporarily raises the pH to values higher than in the mainstream seawater.

We assessed the thickness and the characteristics of the DBL at two pH levels (today's average surface ocean pH 8.1 and a reduced pH predicted for the end of the century, pH 7.7) and seawater flows (slow, 0.5 and fast, >8 cm/s) on Ecklonia radiata (kelp) blades. Oxygen and pH profiles from the blade surface to the mainstream seawater were measured with O2 and pH microsensors for both bare blades and blades colonized by the bryozoan Membranipora membranacea.

The DBL was thicker in slow flow compared with fast flow and the presence of bryozoans increased the DBL thickness and shaped the DBL gradient in dark conditions. Net production was increased in the low pH condition, increasing the amount of oxygen in the DBL in both bare and epiphytized blades. This increase drove the daily pH fluctuations at the blade surface, shifting them towards higher values compared with today's pH. The presence of bryozoans led to lower oxygen concentrations in the DBL and more complex pH fluctuations at the blade surface, particularly at pH 7.7.

Overall, this study, based on microprofiles, shows that, in slow flow, DBL microenvironments at the surface of the kelps may constitute a refuge from OA with pH values higher than those of the mainstream seawater. For calcifying organisms, it could also represent training ground for harsh conditions, with broad daily pH and oxygen fluctuations. These chemical microenvironments, biologically shaped by the macrophytes, are of great interest for the resilience of coastal ecosystems in the context of global change.

A plain language summary is available for this article.
Childhood measles contributes to post‐bronchodilator airflow obstruction in middle‐aged adults: A cohort study
Authors: Perret Jennifer L. , Matheson Melanie C. , Gurrin Lyle C. , Johns David P. , Burgess John A. , Thompson Bruce R. , Lowe Adrian J. , Markos James , Morrison Stephen S. , McDonald Christine F. , Wood‐Baker Richard , Svanes Cecilie , Thomas Paul S. , Hopper John L. , Giles Graham G. , Abramson Michael J. , Walters E. Haydn , Dharmage Shyamali C.
Published: March 2018

Background and objective

Chronic obstructive pulmonary disease (COPD) has potential origins in childhood but an association between childhood measles and post‐bronchodilator (BD) airflow obstruction (AO) has not yet been shown. We investigated whether childhood measles contributed to post‐BD AO through interactions with asthma and/or smoking in a non‐immunized middle‐aged population.

Methods

The population‐based Tasmanian Longitudinal Health Study (TAHS) cohort born in 1961 (n = 8583) underwent spirometry in 1968 before immunization was introduced. A history of childhood measles infection was obtained from school medical records. During the fifth decade follow‐up (n = 5729 responses), a subgroup underwent further lung function measurements (n = 1389). Relevant main associations and interactions by asthma and/or smoking on post‐BD forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC; continuous variable) and AO (FEV1/FVC < lower limit of normal) were estimated by multiple regression.

Results

Sixty‐nine percent (n = 950) had a history of childhood measles. Childhood measles augmented the combined adverse effect of current clinical asthma and smoking at least 10 pack‐years on post‐BD FEV1/FVC ratio in middle age (z‐score: −0.70 (95% CI: −1.1 to −0.3) vs −1.36 (−1.6 to −1.1), three‐way interaction: P = 0.009), especially for those with childhood‐onset asthma. For never‐ and ever‐smokers of <10 pack‐years who had current asthma symptoms, compared with those without childhood measles, paradoxically, the odds for post‐BD AO was not significant in the presence of childhood measles (OR: 12.0 (95% CI: 3.4–42) vs 2.17 (0.9–5.3)).

Conclusion

Childhood measles infection appears to compound the associations between smoking, current asthma and post‐BD AO. Differences between asthma subgroups provide further insight into the complex aetiology of obstructive lung diseases for middle‐aged adults.
Constitucionalización y protección de derechos fundamentales en el contrato de seguros . Análisis jurisprudencial - corte constitucional de Colombia
Authors: Zarante Bahamón Gabriela
Published: March 2018

Este artículo tiene como objeto dar a conocer la tendencia a la “constitucionalización” del Derecho de Seguros y la protección excepcional de la Corte Constitucional a los denominados “Sujetos de Protección Constitucional”. Lo anterior se representa en la manera en que un asegurado o beneficiario de una Póliza Vida Grupo en “estado de indefensión” mediante  una acción de tutela solicita hacer efectivos los amparos de muerte o incapacidad total y permanente sin cumplir con los requisitos contractuales y legales para acceder a dichas coberturas. La posición de la Corte Constitucional, teniendo en cuenta que prevalece el derecho sustancial sobre el procesal, se basa en los principios de solidaridad, inmediatez y subsidiaridad, cuando se invoca la protección de los derechos fundamentales a la vida, mínimo vital, vivienda digna, igualdad, seguridad social entre otros. Se resalta que dicha tutela constitucional, se ha presentado en casos en los cuales las Compañías Aseguradoras han negado el pago de la Indemnización bajo el argumento de haber sido el asegurado reticente por tratarse de una enfermedad preexistente o cuando, por el transcurso del tiempo, el asegurado o beneficiario de la póliza pierde la posibilidad de ejercer el derecho de acción por haber operado el término de prescripción contemplado en la ley Colombiana para el Contrato de Seguros.
Una aproximación a la temática de los seguros en el contexto de la explotación y exploración de hidrocarburos costa afuera
Authors: Signorino Barbat Andrea
Published: March 2018

Sin dudas la exploración y explotación de hidrocarburos costa afuera supone grandes desafíos en la prevención de riesgos que pueden ocurrir en dicho contexto. La pregunta es qué respuesta le puede dar el seguro a estos riesgos y cuáles deberían ser los aspectos a tener en cuenta en este sentido, sobretodo en Uruguay donde este tema es incipiente.
La mala fe y el fraude en derecho colombiano de seguros
Authors: Vásquez Vega Daniel
Published: March 2018

El contrato de seguro es uno en el que la buena fe tiene especial preponderancia y la misma se encuentra presente a lo largo de toda la relación aseguraticia, esto es, en la etapa precontractual, durante la vigencia del seguro e incluso después de ocurrido un siniestro. De igual manera, así como el derecho promueve la buena fe, también procura disuadir el fraude durante todas las mismas etapas. El derecho colombiano no es ajeno a esto y en este sentido al regular el contrato seguro establece una serie de reglas que promocionan la buena fe y desincentivan y castigan la mala fe y el fraude. Estas reglas son, principalmente, las siguientes: a) el deber de declarar sinceramente el estado del riesgo; b) la prohibición de contratar seguros con causas o motivos ilícitos; c) la prohibición de cubrir o asegurar los siniestros ocasionados intencional o dolosamente por el tomador, asegurado o beneficiario d) el deber de presentar las reclamaciones en buena fe; y e) la existencia del principio indemnizatorio en los seguros de daños y la consecuente regulación del sobreseguro y de la coexistencia de seguros.
Los seguros de ‘cyber risk’ (A propósito del ciberataque mundial de fecha 12 de mayo de 2017)
Authors: Sobrino Waldo
Published: March 2018

Con fecha 12 de mayo de 2017 se produjo uno de los más trascendentes ataques globales, donde diferentes hackers produjeron daños a los sistemas de varias empresas en el mundo. Dicho ataque nos brindó una pequeña muestra de lo que puede suceder en el futuro, y –además- también demostró la vulnerabilidad de las empresas. Y una de las enseñanzas que aportó la agresión cibernética, es la demostración que absolutamente todas las empresas se encuentran expuestas a ese riesgo cibernético. Los daños pueden ser desde la generación de ‘responsabilidad civil’ de la empresa por la divulgación de información confidencial propia o ajena, hasta daños ‘patrimoniales’ derivados de los daños al sistema de computación, o –aún mayor- en los casos en que se produzca una ‘interrupción del negocio’ (‘Business Interruption’). En la actualidad ya existen Seguros de ‘Cyber Risk’ en Latinoamérica, donde se puede brindar cobertura para los riesgos de ‘Property’ y ‘Liability’, pero debe resaltarse que existen en el mundo una gran variedad de textos de cobertura del seguro, donde es fundamental analizar los alcances de los riesgos cubiertos y las exclusiones de cobertura.
Emergency Repair
Authors: Testa Bridget Mintz
Published: March 2018

This article states one of the extravehicular activity (EVA) incidence that happened in NASA space station. It also highlights how NASA carefully considers checklists for the emergency repairs and EVAs. EVAs – spacewalks – are planned months, even years in advance. The astronauts who are scheduled to perform them spend hour upon hour practicing them in the controlled environment of the Johnson Space Center in Houston. Expedition 46 Commander Scott Kelly and Flight Engineer Tim Kopra successfully repaired the International Space Station's Mobile Transporter rail car during a three-hour and 16-minute spacewalk—the third for Kelly, and the second for Kopra. The smoothness of the EVA is a testimony to NASA’s ability to handle emergencies. The major lesson learned from the EVA is that a thorough worksite inspection checklist should be made to ensure crew do not leave ISS in a poor configuration after an EVA.
Watching the Crops Grow
Authors: Ferber Dan
Published: March 2018

This article presents an insight into innovations in the field of bioenergy crops. In order to get the most biofuel from the least land, farmers must maximize the yield of raw plant material per acre per year, while using a minimum of fertilizer and chemicals. To rapidly develop crops that do so, sorghum breeders and other scientists want to identify the traits or phenotypes that predict which plants will be biggest and have the most biomass to convert into fuel. Such phenotypes may include early season growth rates, the number of leaves on a plant, how well it uses soil nutrients, and many more. Transportation Energy Resources from Renewable Agriculture-funded team plan to monitor a diverse array of genes and traits in thousands of individual sorghum plants from the ground and the air. They are using robots, UAVs, sensing technologies, and big data to make that happen. In order to monitor crops from the ground, both the Purdue team and Clemson University’s ARPA-E BOOST team are developing self-driving, instrument-equipped bots or vehicles that steer themselves through a breeding plot without trampling plants.
Modeling Cyber Conflict to Inform Critical Infrastructure Defense
Authors: Connett Brian , O’Halloran Bryan
Published: March 2018

This article presents a combination of known models and system design techniques that result in an architectural framework that is predictive. The article also provides a methodical recommendation that develops the way defense of a cyber critical infrastructure can be most effective. Firstly, historical background has been provided to motivate the current political theme, followed by modeling theory that has been published. Classical systems engineering foundations are reviewed to adapt modeling environment to the current cyber conflict problem in a way that allows a systems owner to posture most effectively against anomalies across the network of communication nodes. The implication of the model presented in the article is that a protection posture can be estimated, and can quickly turn into a balanced engagement between the attacker and defender. When optimized within decision algorithms, data will exist to illuminate what process can be implemented in defense. Using classical systems engineering fundamentals, modeling simulation, and proven mathematical approaches, this research seeks to support such implementation.
Cyber-Physical Security Research at UMBC's Eclipse Lab
Authors: Croteau CDR Brien , Krishnankutty Deepak
Published: March 2018

This article focuses on the research and development work at the Eclipse Research Cluster at the University of Maryland, Baltimore County (UMBC) to address cybersecurity challenges. The research team is seeking to address cybersecurity challenges by employing a diverse set of specialty areas including Computer Science, Computer Engineering, and Electrical Engineering. This group is looking at leveraging physical relationships to provide a diversity of measurement and reporting to not only improve anomaly detection, but also make decisions about how to keep critical functions operating even if only in a degraded mode. By exploiting the physical relationships between pressing a brake pedal and the operator’s leg position and the power consumption of a sensor and the instructions being run in it, this group proposes to provide new indicators that can be used to increase resilience to cyberattacks. This concept describes an example for a small section of a typical vehicle system. This group’s future research is seeking to expand this general approach of using the physical relationships of sensors to the properties they are measuring or actuators and the cause or effect of their action.
Evaluation of the Effect of Spar Cap Fiber Angle of Bending–Torsion Coupled Blades on the Aero-Structural Performance of Wind Turbines
Authors: Şener Özgün , Farsadi Touraj , Ozan Gözcü M. , Kayran Altan
Published: March 2018

This paper presents a comprehensive study of the evaluation of the effect of spar cap fiber orientation angle of composite blades with induced bending–torsion coupling (IBTC) on the aero-structural performance wind turbines. Aero-structural performance of wind turbines with IBTC blades is evaluated with the fatigue load mitigation in the whole wind turbine system, tower clearances, peak stresses in the blades, and power generation of wind turbines. For this purpose, a full E-glass/epoxy reference blade has been designed, following the inverse design methodology for a 5-MW wind turbine. An E-glass/epoxy blade with IBTC and novel, hybrid E-glass/carbon/epoxy blades with IBTC have been designed and aeroelastic time-marching multibody simulations of the 5-MW turbine systems, with the reference blade and the blades with IBTC, have been carried out using six different randomly generated turbulent wind profiles. Fatigue-equivalent loads (FELs) in the wind turbine have been determined as an average of the results obtained from the time response of six different simulations. The results reveal that certain hybrid blade designs with IBTC are more effective in fatigue load mitigation than the E-glass–epoxy blade with IBTC, and besides the fiber orientation angle, sectional properties of hybrid blades must be adjusted accordingly using proper number of carbon/epoxy layers in the sections of the blade with IBTC, in order to simultaneously reduce generator power losses and the FEL.
Low-Speed Go-Kart Crash Tests and a Comparison to Activities of Daily
Living
Authors: Kloppenborg Nick , Amenson Tara , Wernik Jacob , Wiechel John
Published: March 2018

Go-karts are a common amusement park feature enjoyed by people of all ages. While intended for racing, contact between go-karts does occur. To investigate and quantify the accelerations and forces which result from contact, 44 low-speed impacts were conducted between a stationary (target) and a moving (bullet) go-kart. The occupant of the bullet go-kart was one of two human volunteers. The occupant of the target go-kart was a Hybrid III 50th percentile male anthropomorphic test device (ATD). Impact configurations consisted of rear-end impacts, frontal impacts, side impacts, and oblique impacts. Results demonstrated high repeatability for the vehicle performance and occupant response. Go-kart accelerations and speed changes increased with increased impact speed. Impact duration and restitution generally decreased with increased impact speed. All ATD acceleration, force, and moment values increased with increased impact speed. Common injury metrics such as the head injury criterion (HIC), Nij, and Nkm were calculated and were found to be below injury thresholds. Occupant response was also compared to published activities of daily living data.
Centrifuge Model Study on the Effect of Lattice Leg and Sleeve on the Postconsolidation Bearing Capacity of Spudcan Foundation
Authors: Li Yu Ping , Yi Jiang Tao , Lee Fook Hou
Published: March 2018

Up to now, the postconsolidation bearing capacity enhancement of jack-up spudcan foundation has been explored using centrifuge model tests and numerical analyses, which however ignored the realistic jack-up lattice leg. This paper investigates both typical lattice leg and sleeve effects on the postconsolidation spudcan bearing capacity using centrifuge model tests, by replicating the entire process of spudcan in normally consolidated clay: “penetration–unloading–consolidation–repenetration.” The experimental results show that the lattice leg and sleeve affect the spudcan bearing capacity in two sides compared with spudcan without leg. First, it increases the transient bearing capacity during initial spudcan penetration; second, less postconsolidation bearing capacity improvement is yielded by the presence of the leg. The former effect is of importance on the prediction of jack-up leg penetration, and the latter effect would suggest a lower risk of spudcan punch-through for realistic offshore jack-up rig during preloading and operation period.
A Novel Time-Variant Reliability Analysis Method Based on Failure Processes Decomposition for Dynamic Uncertain Structures
Authors: Yu Shui , Wang Zhonglai
Published: March 2018

Due to the uncertainties and the dynamic parameters from design, manufacturing, and working conditions, many engineering structures usually show uncertain and dynamic properties. This paper proposes a novel time-variant reliability analysis method using failure processes decomposition to transform the time-variant reliability problems to the time-invariant problems for dynamic structures under uncertainties. The transformation is achieved via a two-stage failure processes decomposition. First, the limit state function with high dimensional input variables and high order temporal parameters is transformed to a quadratic function of time based on the optimized time point in the first-stage failure processes decomposition. Second, based on the characteristics of the quadratic function and reliability criterion, the time-variant reliability problem is then transformed to a time-invariant system reliability problem in the second-stage failure processes decomposition. Then, the kernel density estimation (KDE) method is finally employed for the system reliability evaluation. Several examples are used to verify the effectiveness of the proposed method to demonstrate its efficiency and accuracy.
A Precision System for Computed Tomography-Guided Needle Placement in the Thorax and Abdomen—Technical Design and Performance Analysis
Authors: Arnolli Maarten M. , Buijze Martijn , Franken Michel , Broeders Ivo A. M. J. , Brouwer Dannis M.
Published: March 2018

A system was developed for computed tomography (CT)-guided needle placement in the thorax and abdomen, providing precise aiming of a needle guide (NG) to reach a user-specified target in a single manual insertion. The objective of this work is to present its technical design and analyze its performance in terms of placement error in air. The individual contributions to the placement error of a fiducial marker based system-to-CT registration system, a two degrees-of-freedom (2DOFs) drive system to aim the NG, and a structural link between NG and CT table were experimentally determined, in addition to the placement error of the overall system. An error contribution of 0.81 ± 0.34 mm was determined for the registration system, <1.2 mm and <3.3 mm for the drive system, and 0.35 mm and 0.43 mm for two load cases of the structural link. The overall unloaded system achieved 1.0 ± 0.25 mm and 2.6 ± 0.7 mm at 100 mm and 250 mm depth, respectively. The overall placement errors in air do not exceed the ≤5 mm error specified as a clinical user requirement for needle placement in tissue.