bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophysiological properties of human β-cell lines EndoC-βH1 and -βH2 conform with human β-cells
Authors: Hastoy Benoît , Godazgar Mahdieh , Clark Anne , Nylander Vibe , Spiliotis Ioannis , van de Bunt Martijn , Chibalina Margarita , Barrett Amy , Burrows Carla , Tarasov Andrei , Scharfmann Raphael , Gloyn Anna L. , Rorsman Patrik
Published: November 2017

The electrophysiological and secretory properties of the human β-cell lines EndoC-βH1 and EndoC-βH2 were investigated. Both cell lines respond to glucose (6-20mM) with 2-to 3-fold stimulation of insulin secretion, an effect that was mimicked by tolbutamide (0.2mM) and reversed by diazoxide (0.5mM). Glucose-induced insulin release correlated with an elevation of [Ca2+]i, membrane depolarization and increased action potential firing. KATP channel activity at 1mM glucose is low and increasing glucose to 6 or 20mM reduced KATP channel activity to the same extent as application of the KATP channel blocker tolbutamide (0.2mM). The upstroke of the action potentials in EndoC-βH1 and −βH2 cells observed at high glucose principally reflects activation of L- and P/Q-type Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. Action potential repolarization involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis (measured by measurements of membrane capacitance) was triggered by membrane depolarizations >10ms to membrane potentials above -30mV. Both cell lines were well-granulated (6,000-15,000 granules/cell) and granules consisted of a central insulin core surrounded by a clear halo. We conclude that the EndoC-βH1 and -βH2 cells share many features of primary human β-cells and that they represent a useful experimental model.
UV-Induced Keratin 1 Proteolysis Mediates UV-Induced Skin Damage
Authors: Zhang Mingchao , Maharjan Dhruba Tara , He Hao , Li Yujia , Yan Wei , Yan Weixin , Zhu Yujie , Ying Weihai
Published: November 2017

Keratins play critical roles in intermediate filament formation, inflammatory responses and cellular signaling in epithelium. While keratins is a major epidermal fluorophore, the mechanisms underlying the autofluorescence (AF) of keratins and its biomedical implications have remained unknown. Our study used mouse skin as a model to study these topics, showing that UV dose-dependently induced increases in green AF at the spinous layer of the epidermis of mouse within 6 hr of the UV exposures, which may be used for non-invasive prediction of UV-induced skin damage. The UV-induced AF appears to be induced by cysteine protease-mediated keratin 1 proteolysis: 1) UV rapidly induced significant keratin 1 degradation; 2) administration of keratin 1 siRNA largely decreased the UV-induced AF; and 3) administration of E-64, a cysteine protease inhibitor, significantly attenuated the UV-induced AF and keratin 1 degradation. Our study has also suggested that the UV-induced keratin 1 proteolysis may be a novel crucial pathological factor in UV-induced skin damage, which is supported by both the findings that indicate critical biological roles of keratin 1 in epithelium and our observation that prevention of UV-induced keratin 1 proteolysis can lead to decreased UV-induced skin damage. Collectively, our study has suggested that UV-induced keratin 1 proteolysis may be a novel and valuable target for diagnosis, prevention and treatment of UV-induced skin damage.
Identification and Targeting of Cortical Ensembles
Authors: Carrillo-Reid Luis , Han Shuting , Taralova Ekaterina , Jebara Tony , Yuste Rafael
Published: November 2017

Breaking the neural code requires the characterization of physiological and behavioral correlates of neuronal ensemble activity. To understand how the emergent properties of neuronal ensembles allow an internal representation of the external world, it is necessary to generate empirically grounded models that fully capture ensemble dynamics. We used machine learning techniques, often applied in big data pattern recognition, to identify and target cortical ensembles from mouse primary visual cortex in vivo leveraging recent developments in optical techniques that allowed the simultaneous recording and manipulation of neuronal ensembles with single-cell precision. Conditional random fields (CRFs) allowed us not only to identify cortical ensembles representing visual stimuli, but also to individually target neurons that are functionally key for pattern completion. These results represent the proof-of-principle that machine learning techniques could be used to design close-loop behavioral experiments that involve the precise manipulation of functional cortical ensembles.
Learning a neural response metric for retinal prosthesis
Authors: Shah Nishal P. , Madugula Sasidhar , Chichilnisky E.J. , Shlens Jonathon , Singer Yoram
Published: November 2017

Retinal prostheses for treating incurable blindness are designed to electrically stimulate surviving retinal neurons, causing them to send artificial visual signals to the brain. However, electrical stimulation generally cannot precisely reproduce typical patterns of neural activity in the retina. Therefore, an electrical stimulus must be selected so as to produce a neural response as close as possible to the desired response. This requires a technique for computing the distance between a desired response and an achievable response that is meaningful in terms of the visual signal being conveyed. We propose a method to learn a metric on neural responses directly from recorded light responses of a population of retinal ganglion cells (RGCs) in the primate retina. The learned metric produces a measure of similarity of RGC population responses that accurately reflects the similarity of visual inputs. Using data from electrical stimulation experiments, we demonstrate that the learned metric could produce improvements in the performance of a retinal prosthesis.
ShuTu: Open-Source Software for Efficient and Accurate Reconstruction of Dendritic Morphology
Authors: Jin Dezhe Z. , Zhao Ting , Hunt David L. , Tillage Rachel P. , Hsu Ching-Lung , Spruston Nelson
Published: November 2017

Neurons perform computations by integrating inputs from thousands of synapses – mostly in the dendritic tree – to drive action potential firing in the axon. One fruitful approach to understanding this process is to record from neurons using patch-clamp electrodes, fill the recorded neuron with a substance that allows subsequent staining, reconstruct the three-dimensional architecture of the dendrites, and use the resulting functional and structural data to develop computer models of dendritic integration. Accurately producing quantitative reconstructions of dendrites is typically a tedious process taking many hours of manual inspection and measurement. Here we present ShuTu, a new software package that facilitates accurate and efficient reconstruction of dendrites imaged using bright-field microscopy. The program operates in two steps: (1) automated identification of dendritic process, and (2) manual correction of errors in the automated reconstruction. This approach allows neurons with complex dendritic morphologies to be reconstructed rapidly and efficiently, thus facilitating the use of computer models to study dendritic structure-function relationships and the computations performed by single neurons.

Significance Statement

We developed a software package – ShuTu – that integrates automated reconstruction of stained neurons with manual error correction. This package facilitates rapid reconstruction of the three-dimensional geometry of neuronal dendritic trees, often needed for computational simulations of the functional properties of these structures.
Altered sensitivity to motion of area MT neurons following long-term V1 lesions
Authors: Hagan Maureen A. , Chaplin Tristan A. , Huxlin Krystel R. , Rosa Marcello G. P. , Lui Leo L.
Published: November 2017

The middle temporal area (MT) receives its main afferents from the striate cortex (V1). However, MT also receives direct thalamic projections, which have been hypothesized to play a crucial role in residual vision after V1 lesions. MT neurons continue to respond shortly after V1 lesions, but human clinical work has shown that lesion effects can take up to six months to stabilize, making it important to understand MT responses after long-term deprivation of V1 inputs. We recorded neuronal responses in MT to moving dot stimuli in adult marmoset monkeys, 7-11 months after unilateral V1 lesions. Fewer MT neurons were direction selective, including neurons whose locations corresponded to the intact parts of V1. Firing rates were higher and more variable, and increased with motion strength regardless of direction. These properties could be re-created by a network model with imbalanced inhibition and excitation, providing the first insights into functional implications of long-term plasticity in MT following V1 lesions.
Rescue of an Aggressive Female Sexual Courtship in Mice by CRISPR/cas9 Secondary Mutation in vivo
Authors: Zakany Jozsef , Duboule Denis
Published: November 2017

We had previously reported [1] a mouse line carrying the Atypical female courtship (HoxDAfc) allele, where an ectopic accumulation of Hoxd10 transcripts was observed in a sparse population of cells in the adult isocortex, as a result of a partial deletion of the HoxD gene cluster (Figure 1A). Female mice carrying this allele displayed an exacerbated paracopulatory behavior, culminating in a severe mutilation of the studs’ external genitals. To unequivocally demonstrate that this intriguing phenotype was indeed caused by an illegitimate function of the HOXD10 protein, we use CRISPR/Cas9 technology to induced a microdeletion into the homeobox of the Hoxd10 gene in cis with the HoxDAfc allele [2]. Females carrying this novel HoxDDel(1-9)d10hd allele no longer mutilate males. We conclude that a brain malfunction leading to a severe pathological behavior can be caused by the mere binding to DNA of a transcription factor expressed ectopically. We also show that in HoxDAfc mice, Hoxd10 was expressed in cells containing Gad1 and Cck transcripts, corroborating our proposal that a small fraction of GABAergic neurons in adult hippocampus may participate to some aspects of female courtship.
Effective polyploidy causes phenotypic delay and influences bacterial evolvability
Authors: Sun Lei , Alexander Helen K. , Bogos Balazs , Kiviet Daniel J. , Ackermann Martin , Bonhoeffer Sebastian
Published: November 2017

Whether mutations in bacteria exhibit a noticeable delay before expressing their corresponding mutant phenotype was discussed intensively in the 1940s-50s, but the discussion eventually waned for lack of supportive evidence and perceived incompatibility with observed mutant distributions in fluctuation tests. Phenotypic delay in bacteria is widely assumed to be negligible, despite lack of direct evidence. Here we revisited the question using recombineering to introduce antibiotic resistance mutations intoE. coliat defined time points and then tracking expression of the corresponding mutant phenotype over time. Contrary to previous assumptions, we found a substantial median phenotypic delay of 3-4 generations. We provided evidence that the primary source of this delay is multifork replication causing cells to be effectively polyploid, whereby wild-type gene copies transiently mask the phenotype of recessive mutant gene copies in the same cell. Using modeling and simulation methods, we explored the consequences of effective polyploidy for mutation rate estimation by fluctuation tests and sequencing-based methods. For recessive mutations, despite the substantial phenotypic delay, theper-copyorper-genomemutation rate is accurately estimated. However, theper-cellrate cannot be estimated by existing methods. Finally, with a mathematical model, we showed that effective polyploidy increases the frequency of costly recessive mutations in the standing genetic variation, and thus their potential contribution to evolutionary adaptation, while drastically reducing the chance thatde novorecessive mutations can rescue populations facing a harsh environmental change such as antibiotic treatment. Overall, we have identified phenotypic delay and effective polyploidy as previously overlooked but essential components in bacterial evolvability, including antibiotic resistance evolution.

Author summary

What is the time delay between the occurrence of a genetic mutation in a bacterial cell and manifestation of its phenotypic effect? We show that antibiotic resistance mutations inE.colishow a remarkably long phenotypic delay of 3-4 bacterial generations. The primary underlying mechanism of this delay is effective polyploidy. In a polyploid cell with multiple chromosomes, once a mutation arises on one of the chromosomes, the presence of non-mutated, wild-type gene copies on other chromosomes may mask the phenotype of the mutation. One implication of this finding is that conventional methods to determine the mutation rates of bacteria do not detect polyploidy and thus underestimate their potential for adaptation. More generally, the effect that a new mutation may become useful only in the “grand-children of the grand-children” suggests that pre-existing mutations are more important for surviving sudden environmental catastrophe.
A quantitative PCR based environmental DNA assay for detecting Atlantic salmon (Salmo salar L.)
Authors: Atkinson Siobhán , Carlsson Jeannette E.L. , Ball Bernard , Egan Damian , Kelly-Quinn Mary , Whelan Ken , Carlsson Jens
Published: November 2017

The Atlantic salmon (Salmo salar L.) has worldwide ecological, cultural and economic importance. The species has undergone extensive decline across its native range, yet concerns have been raised about its invasive potential in the Pacific. Knowledge on the distribution of this species is vital for addressing conservation goals.

This study presents an eDNA assay to detect S. salar in water samples, using quantitative PCR (qPCR) technology. Species-specific primers and a minor groove binding (MGB) probe were designed for the assay, based on the mitochondrial cytochrome oxidase I (COI) gene.

The results of this study indicate that eDNA is a highly sensitive tool for detecting S. salar in situ, and could potentially provide an alternative, non-invasive method for determining the distribution of this species.
Transcriptome-wide interrogation of the functional intronome by spliceosome profiling
Authors: Chen Weijun , Moore Jill , Ozadam Hakan , Shulha Hennady P. , Rhind Nicholas , Weng Zhiping , Moore Melissa J.
Published: November 2017

Full understanding of eukaryotic transcriptomes and how they respond to different conditions requires deep knowledge of all sites of intron excision. Although RNA-Seq provides much of this information, the low abundance of many spliced transcripts (often due to their rapid cytoplasmic decay) limits the ability of RNA-Seq alone to reveal the full repertoire of spliced species. Here we present “spliceosome profiling”, a strategy based on deep sequencing of RNAs co-purifying with late stage spliceosomes. Spliceosome profiling allows for unambiguous mapping of intron ends to single nucleotide resolution and branchpoint identification at unprecedented depths. Our data reveal hundreds of new introns inS. pombeand numerous others that were previously misannotated. By providing a means to directly interrogate sites of spliceosome assembly and catalysis genome-wide, spliceosome profiling promises to transform our understanding of RNA processing in the nucleus much like ribosome profiling has transformed our understanding mRNA translation in the cytoplasm.
Reciprocal Disruptions in Thalamic and Hippocampal Resting-State Functional Connectivity in Youth with 22q11.2 Deletions
Authors: Schleifer Charles , Lin Amy , Kushan Leila , Ji Jie Lisa , Yang Genevieve , Bearden Carrie E. , Anticevic Alan
Published: November 2017

22q11.2 deletion syndrome (22q11DS) is a recurrent copy number variant (CNV) with high penetrance for developmental neuropsychiatric disorders. Study of individuals with 22q11DS therefore may offer key insights into neural mechanisms underlying such complex illnesses. Resting-state functional MRI (rs-fMRI) studies in idiopathic schizophrenia have consistently revealed disruption of thalamic and hippocampal circuitry. Here, we sought to test whether this circuitry is similarly disrupted in the context of this genetic high-risk condition. To this end, resting-state functional connectivity patterns were assessed in a sample of young men and women with 22q11DS (n=42) and demographically matched healthy controls (n=39). Neuroimaging data were acquired via single-band protocols, and analyzed in line with methods provided by the Human Connectome Project (HCP). We computed functional relationships between individual-specific anatomically-defined thalamic and hippocampal seeds and all gray matter voxels in the brain. Whole-brain type I error protection was achieved through nonparametric permutation-based methods. 22q11DS patients displayed reciprocal disruptions in thalamic and hippocampal functional connectivity relative to control subjects. Thalamo-cortical coupling was increased in sensorimotor cortex, and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to sensory and associative network connectivity. The thalamic and hippocampal dysconnectivity observed in 22q11DS suggest that high genetic risk for psychiatric illness is linked with disruptions in large-scale cortico-subcortical networks underlying higher-order cognitive functions. These effects highlight the translational importance of large-effect CNVs for informing mechanisms underlying neural disruptions observed in idiopathic developmental neuropsychiatric disorders.

SIGNIFICANCE STATEMENT

Investigation of neuroimaging biomarkers in highly penetrant genetic syndromes represents a more biologically tractable approach to identify neural circuit disruptions underlying developmental neuropsychiatric conditions. 22q11.2 deletion syndrome confers particularly high risk for psychotic disorders, and is thus an important translational model in which to investigate systems-level mechanisms implicated in idiopathic illness. Here, we show resting-state fMRI evidence of large-scale sensory and executive network disruptions in youth with 22q11DS. In particular, this study provides the first evidence that these networks are disrupted in a reciprocal fashion with regard to the functional connectivity of the thalamus and hippocampus, suggesting circuit-level dysfunction.
Soluble amyloid-beta buffering by plaques in Alzheimer disease dementia versus high-pathology controls
Authors: Esparza Thomas J. , Gangolli Mihika , Cairns Nigel J. , Brody David L.
Published: November 2017

An unanswered question regarding Alzheimer disease dementia (ADD) is whether amyloid-beta (Aβ) plaques sequester toxic soluble Aβ species early in the pathological progression. We previously reported that the concentration of soluble Aβ aggregates from patients with mild dementia was higher than soluble Aβ aggregates from patients with modest Aβ plaque burden but no dementia. The ratio of soluble Aβ aggregate concentration to Aβ plaque area fully distinguished these groups of patients. We hypothesized that initially plaques may serve as a reservoir or sink for toxic soluble Aβ aggregates, sequestering them from other targets in the extracellular space and thereby preventing their toxicity. To initially test a generalized version of this hypothesis, we have performed binding assessments using biotinylated synthetic Aβ1-42 peptide. Aβ1-42-biotin peptide was incubated on unfixed frozen sections from non-demented high plaque pathology controls and patients with dementia of the Alzheimer type. The bound peptide was measured using ELISA and confocal microscopy. We observed no quantitative difference in Aβ binding between the groups using either method. Further testing of the buffering hypothesis using various forms of synthetic and human derived soluble Aβ aggregates will be required to definitively address the role of plaque buffering as it relates to ADD.
The crystal structure of Rb2Ti2O5
Authors: Federicci Rémi , Baptiste Benoit , Finocchi Fabio , Popa Florin , Brohan Luc , Béneut Keevin , Giura Paola , Rousse Gwenaëlle , Descamps-Mandine Armel , Douillard Thierry , Shukla Abhay , Leridon Brigitte
Published: November 2017

Recent results have demonstrated an exceptionally high permittivity in the range 200–330 K in crystalline titanium oxide Rb2Ti2O5. In this article, the possibility of a structural transition giving rise to ferroelectricity is carefully inspected. In particular, X-ray diffraction, high-resolution transmission electron microscopy and Raman spectroscopy are performed. The crystal structure is shown to remain invariant and centrosymmetric at all temperatures between 90 K and 450 K. The stability of the C2/m structure is confirmed by density functional theory calculations. These important findings allow the existence of a conventional ferroelectric phase transition to be ruled out as a possible mechanism for the colossal permittivity and polarization observed in this material.
Phase transition and proton ordering at 50 K in 3-(pyridin-4-yl)pentane-2,4-dione
Authors: Truong Khai-Nghi , Merkens Carina , Meven Martin , Faßbänder Björn , Dronskowski Richard , Englert Ulli
Published: November 2017

Single-crystal neutron diffraction experiments at 100 and 2.5 K have been performed to determine the structure of 3-(pyridin-4-yl)pentane-2,4-dione (HacacPy) with respect to its protonation pattern and to monitor a low-temperature phase transition. Solid HacacPy exists as the enol tautomer with a short intramolecular hydrogen bond. At 100 K, its donor···acceptor distance is 2.450 (8) Å and the compound adopts space group C2/c, with the N and para-C atoms of the pyridyl ring and the central C of the acetylacetone substituent on the twofold crystallographic axis. As a consequence of the axial symmetry, the bridging hydrogen is disordered over two symmetrically equivalent positions, and the carbon–oxygen bond distances adopt intermediate values between single and double bonds. Upon cooling, a structural phase transition to the t
2 subgroup P\bar 1 occurs; the resulting twins show an ordered acetylacetone moiety. The phase transition is fully reversible but associated with an appreciable hysteresis in the large single crystal under study: transition to the low-temperature phase requires several hours at 2.5 K and heating to 80 K is required to revert the transformation. No significant hysteresis is observed in a powder sample, in agreement with the second-order nature of the phase transition.
Crystal structure of methyl 2-[5-(2-hydroxyphenyl)-2H-tetrazol-2-yl]acetate
Authors: Lee Seul Gi , Ryu Ji Yeon , Lee Junseong
Published: November 2017

The title compound, C10H10N4O3, was synthesized by the esterification of hydroxyphenyl tetrazole. There is an intramolecular O—H...N hydrogen bond present involving the hydroxy group and the tetrazole ring. The tetrazole ring is inclined to the phenol ring by 2.85 (13)°, while the methyl acetate group is almost normal to the tetrazole ring, making a dihedral angle of 82.61 (14)°. In the crystal, molecules are linked by pairs of C—H...O hydrogen bonds, forming inversion dimers. Within the dimers, the phenol rings are linked by offset π–π interactions [intercentroid distance = 3.759 (2) Å]. There are no further significant intermolecular interactions present in the crystal. The hydroxy group is disordered about positions 2 and 6 on the benzene ring, with a refined occupancy ratio of 0.531 (5):0.469 (5).
Diethyl 1-[(4-methyl-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl)methyl]-1H-1,2,3-triazole-4,5-dicarboxylate
Authors: Boukhssas Salaheddine , Aouine Younas , Faraj Hassane , Alami Anouar , El Hallaoui Abdelilah , Zouihri Hafid
Published: November 2017

In the title compound, C19H22N4O5, the central triazole ring makes dihedral angles of 56.15 (8) and 43.25 (9)° with the oxazole and benzene rings, respectively. The mean planes of the two ethoxycarbonyl groups make dihedral angles of 24.16 (11) and 51.90 (10)° with the triazole ring. Globally, the molecule has a U-shape. In the crystal, molecules are linked by C—H...O and C—H...N hydrogen bonds into supramolecular layers in thebcplane.
(E)-N-{3-[(m-Tolylimino)methyl]pyridin-2-yl}pivalamide
Authors: Atalay Şehriman , Gerçeker Semra , Meral Seher
Published: November 2017

In the title compound, C18H21N3O, the dihedral angle between the pyridine and benzene rings is 30.53 (7)° and the C—C=N—C torsion angle is −170.6 (2)°. An intramolecular N—H...N hydrogen bond generates anS(6) ring. In the crystal, very weak C—H...O hydrogen bonds link the molecules intoC(8) [101] chains. Thetert-butyl methyl groups are disordered over two sets of sites in a 0.783 (4):0.217 (4) ratio.
Expanding gender accountability? Women’s organizations and the state in turkey
Authors: Kardam Nüket , Ertürk Yakin
Published: November 2017

In the 1980s and 1990s, a women’s movement has arisen and begun to mature in Turkey. Women’s organizations representing diverse positions and missions have begun to engage in a dialogue with each other, as well as with the Turkish state, especially with the National Women’s Machinery: “Directorate General on the Status and Problems of Women”. This article explores the reasons for the above developments through an examination of a) the influence of the international women’s rights regime and gender sensitive donor programs, and b) increased openness and diversity within Turkish society. We reach the conclusion that even though these changes are limited, they have important implications, heralding an increased tolerance for compromise on the part of the Turkish state, and a readiness to overcome the traditional dichotomous view of the state (expecting all services from the state or staying completely away from the state) on the part of the women’s organizations. This process has further been legitimized and supported by the international women’s rights regime, whose norms and principles are embodied in many international conference documents and conventions.
The promethean spirit in public administration: Spirituality without crutches
Authors: Miller Hugh T. , Fox Charles
Published: November 2017

This is a cry: “Let us face reality!” This article builds on Friedrich Nietzsche and argues against transcendental truth, which is the basis of spirituality. Instead, we need merely to face up to the radical contingency of life in a multi-cultured society. The rules of ethics and morality are contextual and they change over time. Standards are not found but our discourse and interaction establish them. We need to recall Promethean, who was the hero of humans against the gods and provided humans with out running start. That is really all we have but that can be enough. In public administration, we need to not look to gods, God, or spirituality; but instead we need to look to what Promethean gave us and face our intractable problems with the spirit of Promethean. We need to reject those that say they have The Truth as they seek to impose their version on us by thrusting under our arm pits crutches, which we do not need.
The new contingent workforce: Examining the bridge employment options of mature workers
Authors: Shultz Kenneth S.
Published: November 2017

The dual forces of an increasing dependency ratio and lower labor market participation on the part of mature individuals does not bode well for the American and European Communities. To begin to better understand such macro influences, changing demographic trends in the U.S. and European community with regard to the aging population and workforce participation are reviewed. In addition, recent research which continues to dispel the myth of a negative relationship between age and job performance is reviewed. A more informative way of looking at possible relationships between age and job performance is presented. A variety of contingent work arrangements and flexible employment policies are reviewed as a potential solution to the decreased supply of skilled labor for employers and the need for continued income and community involvement on the part of mature individuals. In addition, a call for a redefinition of how we currently view retirement is sounded. We conclude with recommendations for both employers and mature individuals on dealing with the issues presented.
Treating development networks seriously: What public managers should know
Authors: Maclin Steven A. , Keller Lawrence F.
Published: November 2017

In recent years, local governments have concentrated on revitalizing their local economies through economic development policy, which raises a number of important political and legal issues. However, the political attraction of jobs, the popularity of professional sports, and the public's anticipation of obtaining “big league” status stifle a critical probing of these issues. One result has been a systematic pattern of one-sided interactions in favor of entrepreneurs, particularly those who control professional sports franchises. This pattern threatens to undermine the effectiveness and legitimacy of the development policymaking process. This article clarifies these costly though less obvious issues and provides a framework for considering them more candidly, and hopefully, more effectively.
Moral and marketing differences between the united states and ecuador
Authors: Robertson Christopher J. , Brady Michael K. , Hoffman James J.
Published: November 2017

There has been a genuine lack of emphasis in the management and public policy literature on cultural issues in Latin America. This is particularly evident in the ethics and marketing literature. In this paper, the results from two studies are presented which address moral and marketing differences between the United States and Ecuador. In the first study, a comprehensive survey (which includes vignettes for ecological conservation, bribery, sex discrimination, and child labor dilemmas) is administered to 98 multinational managers from the U.S. and Ecuador. Results indicate that certain
Mood: a review of its antecedents and consequences
Authors: Poon June M. L.
Published: November 2017

This article reviews selected literature on the causes and effects of mood. Theoretical mechanisms for explaining the mood phenomenon are also considered. Finally, some practical implications are discussed and specific recommendations are made for research that will advance our understanding of the mood phenomenon and provide useful information to managers.
The effect of process parameters in fused deposition modelling on bonding degree and mechanical properties
Authors: Li Hongbin , Wang Taiyong , Sun Jian , Yu Zhiqiang
Published: November 2017

Purpose

The purpose of this paper is to study the effects of these major parameters, including layer thickness, deposition velocity and infill rate, on product’s mechanical properties and explore the quantitative relationship between these key parameters and tensile strength of the part.

Design/methodology/approach

A VHX-1000 super-high magnification lens zoom three-dimensional (3D) microscope is utilized to observe the bonding degree between filaments. A temperature sensor is embedded into the platform to collect the temperature of the specimen under different parameters and the bilinear elastic-softening cohesive zone model is used to analyze the maximum stress that the part can withstand under different interface bonding states.

Findings

The tensile strength is closely related to interface bonding state, which is determined by heat transition. The experimental results indicate that layer thickness plays the predominant role in affecting bonding strength, followed by deposition velocity and the effect of infill rate is the weakest. The numerical analysis results of the tensile strength predict models show a good coincidence with experimental data under the elastic and elastic-softened interface states, which demonstrates that the tensile strength model can predict the tensile strength exactly and also reveals the work mechanism of these parameters on tensile strength quantitatively.

Originality/value

The paper establishes the quantitative relationship between main parameters including layer thickness, infill rate and deposition velocity and tensile strength for the first time. The numerically analyzed results of the tensile strength predict model show a good agreement with the experimental result, which demonstrates the effectiveness of this predict model. It also reveals the work mechanism of the parameters on tensile strength quantitatively for the first time.
Immunogenicity of recombinant measles vaccine expressing fusion protein of respiratory syncytial virus in cynomolgus monkeys
Authors: Sawada Akihito , Yunomae Kiyokazu , Nakayama Tetsuo
Published: November 2017

Respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants. Effective vaccines are currently being sought, but no vaccine is thus far available. In our previous study, recombinant AIK‐C measles vaccine expressing the RSV fusion protein (MVAIK/RSV/F) was developed and protective immunity against RSV demonstrated in cotton rats. In the present study, the immunogenicity and protective effects were investigated in three cynomolgus monkeys immunized with MVAIK/RSV/F. Neutralizing test antibodies against RSV were detected and no infectious virus was recovered from the lungs of monkeys immunized with MVAIK/RSV/F after challenge. MVAIK/RSV/F has the potential to inhibit RSV infection.
Afghanistan: In Search for an Alternative Route to Stability
Authors: Shahed Kalam
Published: November 2017

After the US invasion of Afghanistan, while there were some successes in fighting international terrorists in the region, Western attempts at state‐building in Afghanistan remain a dismal failure. After years of Western military involvement, the Taliban insurgency today shows no signs of operational decay or a possible defeat. This article argues that Western engagement in Afghanistan only prolongs civil strife and makes room for more radical elements such as the Islamic State of Iraq and Levant (ISIL) to gain a robust foothold in Afghanistan. Domestic conflicts, with the past involvement of the former Soviet Union and the ongoing Western intervention, have bruised and traumatized Afghan society. What the country now needs is a different form of political process that makes peace and reconciliation a top priority. A transition to a peace process will face multiple hurdles, but given their military and economic sacrifices in Afghanistan, the US and its allies should not flinch, but rather face the challenges boldly.
A monetary plethora and what to do with it: the Bank of Portugal during the Second World War and the postwar period (1931–60)
Authors: Amaral Luciano
Published: November 2017

Until the Second World War the Bank of Portugal (BoP) was a long way from possessing the features normally associated with a central bank. It was still a commercial bank, albeit one that had acquired some central bank functions. The war period was decisive in removing this ambiguity. The change was caused mostly by an unusually large influx of international means of payment (gold and foreign exchange) as a consequence of Portugal's neutrality during the war. However, all of this happened during a very troubled period for the BoP, thanks to the collapse of the gold‐exchange standard. The BoP adapted quickly to the new environment of discretion, government interference, and nationalism, although in a relatively original way: it followed the trend but at the same time retained certain features of a central bank still committed to gold standard principles. The two essential objectives of the BoP were to keep the value of the Portuguese currency stable and to keep interest rates low in order to encourage economic growth. The bank was successful on both counts during the war and the postwar period using a series of non‐conventional instruments.
Resilience in Families in Transition: What Happens When a Parent Is Transgender?
Authors: Dierckx Myrte , Mortelmans Dimitri , Motmans Joz , T'Sjoen Guy
Published: November 2017

Objective

To understand the experiences of both children and parents in families where one of the parent is transgender.

Background

A focus on the family environment can be found in research concerning transgender youth, but this focus is lacking in research on transgender adults. To our knowledge, research so far has not shed light on the experiences of minor children who have witnessed the transition of their parent.

Method

Using the family resilience framework, which is a useful theoretical framework for analyzing family transitions, we conducted in‐depth qualitative interviews with 13 children and 15 parents (8 cisgender and 7 transgender) from 9 families.

Results

Various protective family processes were distinguished in the achievement of adaptive functioning outcomes: family continuity, family communication, significant others' acceptance, and attributing meaning. Hence, the findings from this research clearly show that the gender transition of a parent in itself should not be problematized.

Conclusion

Through good practices and protective processes within the family, the transition of a parent's gender can be accepted by children.

Implications

These findings have implications for families with a transgender parent as well as for anyone working with children and their transgender parents.
Neurophagy, the phagocytosis of live neurons and synapses by glia, contributes to brain development and disease
Authors: Vilalta Anna , Brown Guy C.
Published: November 2017

It was previously thought that neurons were phagocytosed only when dead or dying. However, it is increasingly clear that viable synapses, dendrites, axons and whole neurons can be phagocytosed alive (defined here as neurophagy), and this may contribute to a wide range of developmental, physiological and pathological processes. Phagocytosis of live synapses, dendrites and axons by glia contributes to experience‐dependent sculpting of neuronal networks during development, but excessive phagocytosis of synapses may contribute to pathology in Alzheimer's disease, schizophrenia and ageing. Neurons can expose phosphatidylserine or calreticulin, which act as ‘eat me’ signals provoking phagocytosis via microglial receptors, whereas sialylation of neuronal surfaces acts as a ‘don't eat me’ signal that inhibits phagocytosis and desialylation can provoke phagocytosis. Opsonins, such as complement components and apolipoproteins, are released during inflammation and enhance engulfment. Phagocytosis of neurons is seen in multiple human diseases, but it is as yet unclear whether inhibition of phagocytosis will be beneficial in treating neurological diseases. Here we review the signals regulating glial phagocytosis of live neurons and synapses, and the involvement of this phagocytosis in development and disease.
The Baboon Spider Atlas – using citizen science and the ‘fear factor’ to map baboon spider (Araneae: Theraphosidae) diversity and distributions in Southern Africa
Authors: Campbell Heather , Engelbrecht Ian
Published: November 2017

Charismatic invertebrates are popular subjects for citizen science but it is harder to engage the public in research on animals that are perceived as dangerous. Many successful citizen science projects exist in North America and Europe, but with the increased use of new technologies and social media, there is a greater capacity to expand citizen science to less developed regions.

Baboon spiders are African members of the tarantula family. They are threatened by habitat loss and illegal harvesting for the pet trade, and conservation efforts are hampered by a lack of knowledge on their ecology.

Here, we describe the Baboon Spider Atlas, a project combining traditional research with citizen science to map the diversity and distributions of baboon spiders (Araneae: Theraphosidae) in Southern Africa. Our project embraces the ‘fear factor’ associated with spiders to obtain photographic records from the public.

The Baboon Spider Atlas has assembled the largest database of information on baboon spiders in Southern Africa and is providing novel insights into their biology. Distribution ranges have been extended and potential new species discovered. Preliminary results suggest that their distribution may be limited more by cold, wet climatic conditions than hot, dry conditions. Records for wandering adult females and immatures highlight a previously undocumented behaviour and challenges the notion that baboon spiders are sedentary animals. Ultimately, the project is generating the data needed for effective conservation and motivating further research that will provide a better understanding of baboon spider biology.
Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein
Authors: Huang Feng , Chen Jingliang , Zhang Junsong , Tan Likai , Lu Gui , Luo Yongjie , Pan Ting , Liang Juanran , Li Qianwen , Luo Baohong , Zhang Hui , Lu Gen
Published: November 2017

Although antiviral drugs are available for the treatment of influenza infection, it is an urgent requirement to develop new antiviral drugs regarding the emergence of drug‐resistant viruses. The nucleoprotein (NP) is conserved among all influenza A viruses (IAVs) and has no cellular equivalent. Therefore, NP is an ideal target for the development of new IAV inhibitors. In this study, we identified a novel anti‐influenza compound, ZBMD‐1, from a library of 20,000 compounds using cell‐based influenza A infection assays. We found that ZBMD‐1 inhibited the replication of H1N1 and H3N2 influenza A virus strains in vitro, with an IC50 ranging from 0.41–1.14 μM. Furthermore, ZBMD‐1 inhibited the polymerase activity and specifically impaired the nuclear export of NP. Further investigation indicated that ZBMD‐1 binds to the nuclear export signal 3 (NES3) domain and the dimer interface of the NP pocket. ZBMD‐1 also protected mice that were challenged with lethal doses of A/PR/8/1934 (H1N1) virus, effectively relieving lung histopathology changes, as well as strongly inhibiting the expression of pro‐inflammatory cytokines/chemokines, without inducing toxicity effects in mice. These results suggest that ZBMD‐1 is a promising anti‐influenza compound which can be further investigated as a useful strategy against IAVs in the future.
Gingival crevicular fluid and its immune mediators in the proteomic era
Authors: Bostanci Nagihan , Belibasakis Georgios N.
Published: November 2017

The discovery of biomarkers for periodontal disease requires an in‐depth understanding of the molecular basis of the initiation and progression of the disease. The gingival crevicular fluid is a biological medium suitable for identifying and measuring such biomarkers because it can be easily and noninvasively sampled from the immediate vicinity of the affected tissues. An ever‐expanding pool of gingival crevicular fluid proteins associated with periodontal health or disease has been catalogued over the years, particularly with the recent implementation of proteomic technologies. ‘Proteomics’ refers to the large‐scale study of entire arrays of proteins expressed by a genome and present in a cell, tissue, biological fluid or organism. Hence, such technologies provide a broad qualitative and quantitative insight of the proteins present in gingival crevicular fluid. Pertinent studies have amassed on the information gathered to date on protein signatures in periodontal health and disease, and have confirmed the nature of the immunological host response. This review discusses the application of proteomic technologies in characterizing the molecular networks present in gingival crevicular fluid, their potential for discovery of biomarkers that are meaningful for clinical practice, and the associated technical challenges.
HLA‐A*30:125 shows a new antigen binding domain created from HLA‐A*30:01 and HLA‐A*30:02
Authors: Balas A. , Alenda R. , Moreno‐Hidalgo M. A. , García‐Sánchez F. , Vicario J. L.
Published: November 2017

A new HLA‐A allele, A*30:125, was characterized in a Spanish individual.
Efficacy and safety of a new human fibrinogen concentrate in patients with congenital fibrinogen deficiency: an interim analysis of a Phase III trial
Authors: Lissitchkov Toshko , Madan Bella , Djambas Khayat Claudia , Zozulya Nadezhda , Ross Cecil , Karimi Mehran , Kavakli Kaan , De Angulo Guillermo R. , Almomen Abdulkareem , Schwartz Bruce A. , Solomon Cristina , Knaub Sigurd , Peyvandi Flora
Published: November 2017

BACKGROUND

Fibrinogen concentrate is the preferred choice for fibrinogen replacement in congenital fibrinogen deficiency. This study investigated hemostatic efficacy of a new plasma‐derived, double virus‐inactivated (using two dedicated virus inactivation/elimination steps) human fibrinogen concentrate for on‐demand treatment of bleeding episodes (BEs) and surgical prophylaxis.

STUDY DESIGN AND METHODS

In this planned interim analysis of a prospective, multinational Phase III study (NCT02267226), 13 patients with afibrinogenemia (≥12 years) received fibrinogen concentrate (FIBRYGA, Octapharma AG). Hemostatic efficacy was assessed by investigators and an independent data monitoring and endpoint adjudication committee (IDMEAC) using objective four‐point criteria and by thromboelastometry maximum clot firmness (MCF).

RESULTS

Fibrinogen concentrate was used on‐demand to treat 23 BEs in 11 patients, with 21 (91.3%) requiring a single infusion only. Treatment success was 95.7% (90% confidence interval [CI], 0.81‐1.00; assessment missing for one BE) by investigators and 100% (90% CI, 0.88‐1.00) by IDMEAC. Mean MCF increased significantly from 0.0 to 6.5 mm (95% CI, 5.65‐7.40; p < 0.0001) at 1 hour postinfusion of a median (range) dose of 58.8 (33.9‐101.7) mg/kg per BE. Four patients received fibrinogen concentrate as surgical prophylaxis, with intraoperative and postoperative treatment success rated 100% (90% CI, 0.50‐1.00) by investigators and IDMEAC (median [range] dose per surgery 93.5 [34.1‐225.4] mg/kg). No additional hemostatic interventions were required. No deaths, thromboses, or seroconversions were reported.

CONCLUSION

These data showed that the new fibrinogen concentrate was efficacious for on‐demand treatment of acute bleeding and surgical prophylaxis in congenital afibrinogenemia patients.
Influence of the Spatial and Temporal Interaction Between Diesel Pilot and Directly Injected Natural Gas Jet on Ignition and Combustion Characteristics
Authors: Fink Georg , Jud Michael , Sattelmayer Thomas
Published: November 2017

In this paper, pilot-ignited high pressure dual-fuel (HPDF) combustion of a natural gas jet is investigated on a fundamental basis by applying two separate single-hole injectors to a rapid compression expansion machine (RCEM). A Shadowgraphy system is used for optical observations, and the combustion progress is assessed in terms of heat release rates. The experiments focus on the combined influence of injection timing and geometrical jet arrangement on the jet interaction and the impact on the combustion process. In a first step, the operational range for successful pilot self-ignition and transition to natural gas jet combustion is determined, and the restricting phenomena are identified by analyzing the shadowgraph images. Within this range, the combustion process is assessed by evaluation of ignition delays and heat release rates. Strong interaction is found to delay or even prohibit pilot ignition, while it facilitates a fast and stable onset of the gas jet combustion. Furthermore, it is shown that the heat release rate is governed by the time of ignition with respect to the start of natural gas injection — as this parameter defines the level of premixing. Evaluation of the time of gas jet ignition within the operability map can therefore directly link a certain spatial and temporal interaction to the resulting heat release characteristics. It is finally shown that controlling the heat release rate through injection timing variation is limited for a certain angle between the two jets.