bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational design of foundations on soil reinforced by columns
Authors: Bouassida Mounir
Published: September 2016

This paper presents a review of the book titled “Design of column-reinforced foundations” that I recently published. The design of foundations on reinforced soil by columns is tackled within a general framework, where several aspects are taken into consideration: modeling of reinforced soil, bearing capacity, settlement, acceleration of consolidation, and improvement of soil characteristics with selected case histories. Unlike existing books on unique improvement techniques (deep soil mixing, stone columns, sand compaction piles) that focus on installation and equipment issues, this one-of-a-kind guide details design purpose. This book rationally handles the design of column-reinforced foundations (CRF) from modeling up to the study of behavior predicted by the numerical analysis and assessed by the field test results. Quasi-exact solutions of the ultimate bearing capacity of soil reinforced by a trench are suggested. The analytical solutions for predicting the settlement of CRF assuming the linear elastic behavior of constituents of soil reinforced by a group of columns are proposed. A novel methodology for the design of CRF is presented and illustrated by different study cases. The improvement of properties of the initial soil due to the installation of stone columns has been evidenced using numerical and experimental investigations. The behavior of foundations resting on soil reinforced by columns has been predicted by numerical 2D and 3D codes. Related results have been assessed after in situ data.
Internal solitary waves in a two-fluid system with a free surface
Authors: Kodaira Tsubasa , Waseda Takuji , Miyata Motoyasu , Choi Wooyoung
Published: September 2016

Internal solitary waves in a system of two fluids, silicone oil and water, bounded above by a free surface are studied both experimentally and theoretically. By adjusting an extra volume of silicone oil released from a reservoir, a wide range of amplitude waves are generated in a wave tank. Wave profiles as well as wave speeds are measured using multiple wave probes and are then compared with both the weakly nonlinear Korteweg–de Vries (KdV) models and the strongly nonlinear Miyata–Choi–Camassa (MCC) models. As the density difference between the two fluids in the experiment is relatively small (approximately 14 %), but non-negligible, special attention is paid to the effect of the boundary condition at the top surface. The nonlinear models valid for rigid-lid (RL) and free-surface (FS) boundary conditions are considered separately. It is found that the solitary wave of the FS model for a given amplitude is consistently narrower than that of the RL model and it propagates at a slightly lower speed. Due to strong nonlinearity in the internal-wave motion, the weakly nonlinear KdV models fail to describe the measured internal solitary wave profiles of intermediate and large wave amplitudes. The strongly nonlinear MCC-FS model agrees better with the measurements than the MCC-RL model, which indicates that the free-surface boundary condition at the top surface is crucial in describing the internal solitary waves in the experiment correctly. Leaving the top surface free in the experiment allows us to observe small and relatively short wave packets on the top surface, particularly when the amplitude of the internal solitary wave is large. Once excited, the wave packet is located above the front half of the internal solitary wave and propagates with a speed close to that of the internal solitary wave underneath. A simple resonance mechanism between short surface waves and long internal waves without and with nonlinear effects is examined to estimate the characteristic wavelength of modulated short surface waves, which is found to be in good agreement with the observed wavelength when nonlinearity is taken into account. Using ray theory, the evolution of short surface waves in the presence of a background current induced by an internal solitary wave is also investigated to examine the location of the modulated surface wave packet.
Regeneration of turbulent fluctuations in low-Froude-number flow over a sphere at a Reynolds number of 3700
Authors: Pal Anikesh , Sarkar Sutanu , Posa Antonio , Balaras Elias
Published: September 2016

Direct numerical simulations (DNS) are performed to study the behaviour of flow past a sphere in the regime of high stratification (low Froude number $Fr$). In contrast to previous results at lower Reynolds numbers, which suggest monotone suppression of turbulence with increasing stratification in flow past a sphere, it is found that, below a critical $Fr$, increasing the stratification induces unsteady vortical motion and turbulent fluctuations in the near wake. The near wake is quantified by computing the energy spectra, the turbulence energy equation, the partition of energy into horizontal and vertical components, and the buoyancy Reynolds number. These diagnostics show that the stabilizing effect of buoyancy changes flow over the sphere to flow around the sphere. This qualitative change in the flow leads to a new regime of unsteady vortex shedding in the horizontal planes and intensified horizontal shear which result in turbulence regeneration.
Estimation of unsteady aerodynamic forces using pointwise velocity data
Authors: Gómez F. , Sharma A. S. , Blackburn H. M.
Published: September 2016

A novel method to estimate unsteady aerodynamic force coefficients from pointwise velocity measurements is presented. As opposed to other existing methodologies, time-resolved full velocity fields are not required. The methodology is based on a resolvent-based reduced-order model which requires the mean flow to obtain physical flow structures and pointwise measurement to calibrate their amplitudes. A computationally affordable time-stepping methodology to obtain resolvent modes in non-trivial flow domains is introduced and compared with previous existing matrix-free and matrix-forming strategies. The technique is applied to the unsteady flow around an inclined square cylinder at low Reynolds number. The potential of the methodology is demonstrated through good agreement between the fluctuating pressure distribution on the cylinder and the temporal evolution of the unsteady lift and drag coefficients predicted by the model and those computed by direct numerical simulation.
Demand-driven Service Innovation: Discovery and Analysis in Chinese Law Libraries
Authors: Ming Liu
Published: September 2016

This article introduces readers to a new perspective on meeting library user needs. The author employs Kano theory to examine library user demands in Chinese law libraries and how law libraries in China have tried to meet user needs on three different levels. The Kano model was first introduced by Professor Noriaki Kano of Tokyo Rika University. The model was based on the assumption that customer needs are constantly changing and the question becomes how to meet library users’ evolving demands. The article summarizes demands of Chinese law library patrons on three levels: basic needs, performance, and excitement demands. Currently, most Chinese academic law libraries meet the basic needs of library users, but they need to further enhance user satisfaction and promote the law libraries’ status as a legal information center instead of merely a place to collect and house books.
Discipline and Divinity: Colonial Quakerism, Christianity, and “Heathenism” in the Seventeenth Century
Authors: Plank Geoffrey
Published: September 2016

Quakers began arriving in the Caribbean and North America when their religious society was still new and struggling to define its core beliefs and institutional structure. There were tensions within the Society of Friends stemming from the Quakers’ validation of individual inspiration and their communal commitment to the Christian message as contained in the Bible. A bitter debate over scriptural authority wracked Quaker meetings for the remainder of the seventeenth century, and the controversy included arguments over the Quakers’ relations with Native Americans, Africans, and others outside of Europe beyond the reach of formal Christian teaching. On both sides of the Atlantic opponents of Quaker discipline challenged long-standing assumptions about the source and content of the Christian message and the social hierarchies that resulted when some groups claimed privileged access to truth. The ensuing argument influenced the Quakers’ plans for their colonies in North America, and their debate over slavery.
Was Martha of Bethany Added to the Fourth Gospel in the Second Century?
Authors: Schrader Elizabeth
Published: September 2016

This study examines the text transmission of the figure of Martha of Bethany throughout the Fourth Gospel in over one hundred of our oldest extant Greek and Vetus Latina witnesses. The starting point for this study is instability around Martha in our most ancient witness of John 11–12, Papyrus 66. By looking at P66’s idiosyncrasies and then comparing them to the Fourth Gospel's greater manuscript transmission, I hope to demonstrate that Martha's presence shows significant textual instability throughout the Lazarus episode, and thus that this Lukan figure may not have been present in a predecessor text form of the Fourth Gospel that circulated in the second century. In order to gain the greatest amount of data on the Fourth Gospel's text transmission, I rely on several sources. Occasionally these sources conflict in their rendering of a variant; I have tried to make note of these discrepancies and look at photographs of witnesses whenever possible. Although this study is primarily focused on Greek and Vetus Latina witnesses, an occasional noteworthy variant (e.g., from a Syriac or Vulgate witness) may be mentioned when relevant to the subject at hand. The work of many established redaction critics, who have already hypothesized that Martha was not present in an earlier form of this Gospel story, will also be addressed.
A survey of ENT experience in South West Peninsula general practitioner trainees: how can post-graduate ENT training be improved?
Authors: Easto R H , Reddy V
Published: September 2016

Objectives:

To assess how much ENT experience regional general practitioner trainees received, both in their undergraduate and post-graduate training, and to establish if trainees felt they required further ENT training to manage ENT complaints.

Methods:

An online survey was emailed to general practitioner trainees in Cornwall and Devon.

Results:

Of 200 general practitioner trainees, 121 (60.5 per cent) responded to the survey. Of these respondents, 95.9 per cent felt ENT experience was important as a general practitioner; however, 59.5 per cent had no ENT experience in their post-graduate training. Sixty-five per cent of trainees had not had any formal ENT teaching since leaving medical school; however, 93.4 per cent would attend a 1-day course if offered the opportunity locally. Finally, 75.8 per cent of trainees would have liked an ENT post during their post-graduate training.

Conclusion:

Further ENT training is required for doctors in general practitioner training schemes to aid improvement of patient care. The most logical way to enhance ENT training in a post-graduate setting is through up-to-date courses held locally with a faculty made up of experts working within the specialty.
Autologous fat injection therapy including a high concentration of adipose-derived regenerative cells in a vocal fold paralysis model: animal pilot study
Authors: Nishio N , Fujimoto Y , Suga K , Iwata Y , Toriyama K , Takanari K , Kamei Y , Yamamoto T , Gotoh M
Published: September 2016

Objectives:

To verify the effectiveness and safety of the addition of adipose-derived regenerative cells to autologous fat injection therapy.

Methods:

Unilateral vocal fold paralysis models were made by cutting the right recurrent laryngeal nerve in two pigs. At day 30, 0.5 ml adipose-derived regenerative cells mixed with 1 ml autologous fat was injected into the right vocal fold of one pig, with the other receiving 0.5 ml Ringer's solution mixed with 1 ml autologous fat. At day 120, fibrescopy, laser Doppler flowmeter, computed tomography, vocal function evaluation and histological assessment were conducted.

Results:

Although histological assessment revealed atrophy of the thyroarytenoid muscle fibre in both pigs, there was remarkable hypertrophy of the thyroarytenoid muscle fibre in the area surrounding the adipose-derived regenerative cells injection site.

Conclusion:

The addition of a high concentration of adipose-derived regenerative cells to autologous fat injection therapy has the potential to improve the treatment outcome for unilateral vocal fold paralysis.
A systematic review with meta-analysis of the role of anxiety and depression in irritable bowel syndrome onset
Authors: Sibelli A. , Chalder T. , Everitt H. , Workman P. , Windgassen S. , Moss-Morris R.
Published: September 2016

Background

It is well established that people with irritable bowel syndrome (IBS) have higher levels of anxiety and depression compared with controls. However, the role of these as risk factors is less clearly established. The aims of this systematic review were to investigate: (1) whether anxiety and/or depression predict IBS onset; (2) the size of the relative risk (RR) of anxiety versus depression in IBS onset. Subgroup analyses explored if methodological factors affected the overall findings.

Method

Prospective cohort or case–control studies were included if they: (1) focused on the development of IBS in population-based or gastroenteritis cohorts; (2) explored the effects of anxiety and/or depression at baseline as predictors of IBS onset at a future point. In all, 11 studies were included of which eight recruited participants with a gastrointestinal infection. Meta-analyses were conducted.

Results

The risk of developing IBS was double for anxiety cases at baseline compared with those who were not [RR 2.38, 95% confidence interval (CI) 1.58–3.60]. Similar results were found for depression (RR 2.06, 95% CI 1.44–2.96). Anxiety and depression seemed to play a stronger role in IBS onset in individuals with a gastrointestinal infection although this could be attributed to other differences in methodology, such as use of diagnostic interviews rather than self-report.

Conclusions

The findings suggest that self-reported anxiety and depression provide a twofold risk for IBS onset. There is less support for the role of anxiety or depressive disorder diagnosed using clinical interview. These findings may have implications for the development of interventions focused on IBS prevention and treatment.
The Threshold Probability for Long Cycles
Authors: GLEBOV ROMAN , NAVES HUMBERTO , SUDAKOV BENNY
Published: September 2016

For a given graph G of minimum degree at least k, let Gp denote the random spanning subgraph of G obtained by retaining each edge independently with probability p = p(k). We prove that if p ⩾ (logk + loglogk + ωk(1))/k, where ωk(1) is any function tending to infinity with k, then Gp asymptotically almost surely contains a cycle of length at least k + 1. When we take G to be the complete graph on k + 1 vertices, our theorem coincides with the classic result on the threshold probability for the existence of a Hamilton cycle in the binomial random graph.
Effect of socio-economic status on cognitive control in non-literate bilingual speakers
Authors: NAIR VISHNU KK , BIEDERMANN BRITTA , NICKELS LYNDSEY
Published: September 2016

Previous research has suggested that the advantages for cognitive control abilities in bilinguals are attenuated when socio-economic status (SES) is controlled (e.g., Morton & Harper, 2007). This study examined the effect of SES on cognitive control in illiterate monolingual and bilingual individuals who lived in adverse social conditions. We tested monolinguals and bilinguals using Simon and Attentional Network task while controlling for two potential confounding factors: SES and literacy. Bilinguals were faster for both trials with and without conflict demonstrating overall faster response times (global advantage) compared to monolinguals on both tasks. However, no bilingual advantage was found for conflict resolution on the Simon task and attentional networks on the Attentional Network task. The overall bilingual effects provide evidence for a bilingual advantage even among individuals without literacy skills and of very low SES. This indicates a strong link between bilingualism and cognitive control over and above effects of SES.
MODELLING AND SIMULATION OF VOLUMETRIC RAINFALL FOR A CATCHMENT IN THE MURRAY–DARLING BASIN
Authors: BOLAND J. , HOWLETT P. , PIANTADOSI J. , ZAKARIA R.
Published: September 2016

We discuss modelling and simulation of volumetric rainfall in a catchment of the Murray–Darling Basin – an important food production region in Australia that was seriously affected by a recent prolonged drought. Consequently, there has been sustained interest in development of improved water management policies. In order to model accumulated volumetric catchment rainfall over a fixed time period, it is necessary to sum weighted rainfall depths at representative sites within each sub-catchment. Since sub-catchment rainfall may be highly correlated, the use of a Gamma distribution to model rainfall at each site means that catchment rainfall is expressed as a sum of correlated Gamma random variables. We compare four different models and conclude that a joint probability distribution for catchment rainfall constructed by using a copula of maximum entropy is the most effective.
VARIÉTÉS DE KISIN STRATIFIÉES ET DÉFORMATIONS POTENTIELLEMENT BARSOTTI-TATE
Authors: Caruso Xavier , David Agnès , Mézard Ariane
Published: September 2016

Let $F$ be a unramified finite extension of $\mathbb{Q}_{p}$ and $\overline{\unicode[STIX]{x1D70C}}$ be an irreducible mod $p$ two-dimensional representation of the absolute Galois group of $F$. The aim of this article is the explicit computation of the Kisin variety parameterizing the Breuil–Kisin modules associated to certain families of potentially Barsotti–Tate deformations of $\overline{\unicode[STIX]{x1D70C}}$. We prove that this variety is a finite union of products of $\mathbb{P}^{1}$. Moreover, it appears as an explicit closed connected subvariety of $(\mathbb{P}^{1})^{[F:\mathbb{Q}_{p}]}$. We define a stratification of the Kisin variety by locally closed subschemes and explain how the Kisin variety equipped with its stratification may help in determining the ring of Barsotti–Tate deformations of $\overline{\unicode[STIX]{x1D70C}}$.
Neurobiological Correlates of Psychological Treatments for Insomnia
Authors: Marques Daniel Ruivo , Gomes Ana Allen , Clemente Vanda , dos Santos José Moutinho , Caetano Gina , Castelo-Branco Miguel
Published: September 2016

Abstract. Sleep disorders and sleep disturbances are considered nowadays a major public health problem. Within sleep problems, insomnia is the most common health complaint. The maintenance of insomnia symptoms may lead to a clinical disorder – Insomnia Disorder (ID). A significant amount of literature has shown the efficacy and effectiveness of psychological treatments for ID. Often, the evaluation of therapeutic processes and outcomes focuses on subjective measures such as sleep diaries. In this work, we review the few published studies that evaluate modifications in neurobiological domain related to evidence-based psychological interventions, namely cognitive-behavioral therapy for insomnia (CBT-I). The search was carried out consulting Scopus, PubMed, and ISI Web of Knowledge databases. Only 12 studies were found. From the reviewed papers it was observed that the results are diverse, perhaps due to significant differences pertaining to the methodologies used. However, one interesting finding emerged: daytime experiments on insomnia comprising mainly cognitive tasks denoted hypofunction in ID patients, whereas nighttime experiments mainly associated with affective/emotional tasks denoted hyperarousal. We suggest that the study of the neural changes prompted by CBT-I is a major topic in the domain of psychotherapy and sleep medicine. Despite the scarce studies on neurobiological mechanisms of CBT-I, the results achieved until now are promising and should be taken into account in the future. Nonetheless, more research on this topic is needed.
Clearance of autophagy-associated dying retinal pigment epithelial cells – a possible source for inflammation in age-related macular degeneration
Authors: Szatmári-Tóth M , Kristóf E , Veréb Z , Akhtar S , Facskó A , Fésüs L , Kauppinen A , Kaarniranta K , Petrovski G
Published: September 2016

Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis.
MiR-182-5p protects inner ear hair cells from cisplatin-induced apoptosis by inhibiting FOXO3a
Authors: Li Yimeng , Li Ao , Wu Jingfang , He Yingzi , Yu Huiqian , Chai Renjie , Li Huawei
Published: September 2016

Cisplatin is widely used for chemotherapy of a variety of malignancies. However, the clinical application of cisplatin is hampered by the resultant irreversible hearing loss due to hair cell apoptosis. To date, no practical regimen to resolve this has been developed. Meanwhile, the role of microRNA in protecting hair cells from cisplatin-induced apoptosis in the inner ear has not been extensively investigated. In this study, we monitored miR-183, -96, and -182 turnover in the cochlea during cisplatin treatmentin vitro. We found that overexpression of miR-182, but not miR-183 and -96, improved hair cell survival after 3 μM cisplatin treatmentin vitro. We demonstrated that overexpression of miR-182 repressed the intrinsic apoptotic pathway by inhibiting the translation of FOXO3a. Our study offers a new therapeutic target for alleviating cisplatin-induced hair cell apoptosis in a rapid and tissue-specific manner.
Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model
Authors: Drinkut Anja , Tillack Karsten , Meka Durga P , Schulz Jorg B , Kügler Sebastian , Kramer Edgar R
Published: September 2016

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF’s neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF’s effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD.
Omentin protects against LPS-induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS-dependent mechanism
Authors: Qi Di , Tang Xumao , He Jing , Wang Daoxin , Zhao Yan , Deng Wang , Deng Xinyu , Zhou Guoqi , Xia Jing , Zhong Xi , Pu Shenglan
Published: September 2016

Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary inflammation and endothelial barrier permeability. Omentin has been shown to benefit obesity-related systemic vascular diseases; however, its effects on ARDS are unknown. In the present study, the level of circulating omentin in patients with ARDS was assessed to appraise its clinical significance in ARDS. Mice were subjected to systemic administration of adenoviral vector expressing omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh-omentin) to examine omentin’s effects on lipopolysaccharide (LPS)-induced ARDS. Pulmonary endothelial cells (ECs) were treated with rh-omentin to further investigate its underlying mechanism. We found that a decreased level of circulating omentin negatively correlated with white blood cells and procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary ECs with rh-omentin attenuated inflammatory response and restored adherens junctions (AJs), and cytoskeleton organization promoted endothelial barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC survival and differentiation was blocked by the Akt/eNOS pathway inactivation. Therapeutic rh-omentin treatment also effectively protected against LPS-induced ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin protects against LPS-induced ARDS by suppressing inflammation and promoting the pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent mechanism. Therapeutic strategies aiming to restore omentin levels may be valuable for the prevention or treatment of ARDS.
Distal regulation of c-myb expression during IL-6-induced differentiation in murine myeloid progenitor M1 cells
Authors: Zhang Junfang , Han Bingshe , Li Xiaoxia , Bies Juraj , Jiang Penglei , Koller Richard P , Wolff Linda
Published: September 2016

The c-Myb transcription factor is a major regulator that controls differentiation and proliferation of hematopoietic progenitor cells, which is frequently deregulated in hematological diseases, such as lymphoma and leukemia. Understanding of the mechanisms regulating the transcription of c-myb gene is challenging as it lacks a typical promoter and multiple factors are involved. Our previous studies identified some distal regulatory elements in the upstream regions of c-myb gene in murine myeloid progenitor M1 cells, but the detailed mechanisms still remain unclear. In the present study, we found that a cell differentiation-related DNase1 hypersensitive site is located at a −28k region upstream of c-myb gene and that transcription factors Hoxa9, Meis1 and PU.1 bind to the −28k region. Circular chromosome conformation capture (4C) assay confirmed the interaction between the −28k region and the c-myb promoter, which is supported by the enrichment of CTCF and Cohesin. Our analysis also points to a critical role for Hoxa9 and PU.1 in distal regulation of c-myb expression in murine myeloid cells and cell differentiation. Overexpression of Hoxa9 disrupted the IL-6-induced differentiation of M1 cells and upregulated c-myb expression through binding of the −28k region. Taken together, our results provide an evidence for critical role of the −28k region in distal regulatory mechanism for c-myb gene expression during differentiation of myeloid progenitor M1 cells.
Unconventional charge order in a co-doped high-Tc superconductor
Authors: Pelc D. , Vučković M. , Grafe H. -J. , Baek S. -H. , Požek M.
Published: September 2016

Charge-stripe order has recently been established as an important aspect of cuprate high-Tcsuperconductors. However, owing to the complex interplay between competing phases and the influence of disorder, it is unclear how it emerges from the parent high-temperature state. Here we report on the discovery of an unconventional ordered phase between charge-stripe order and (pseudogapped) metal in the cuprate La1.8−xEu0.2SrxCuO4. We use three complementary experiments—nuclear quadrupole resonance, nonlinear conductivity and specific heat—to demonstrate that the order appears through a sharp phase transition and exists in a dome-shaped region of the phase diagram. Our results imply that the new phase is a state, which preserves translational symmetry: a charge nematic. We thus resolve the process of charge-stripe development in cuprates, show that this nematic phase is distinct from high-temperature pseudogap and establish a link with other strongly correlated electronic materials with prominent nematic order.
Correction: Corrigendum: A global reanalysis of storm surges and extreme sea levels
Authors: Muis Sanne , Verlaan Martin , Winsemius Hessel C. , Aerts Jeroen C. J. H. , Ward Philip J.
Published: September 2016

Nature Communications 7: Article number: 11969 (2016); Published: 27 June 2016; Updated: 8 September 2016 In Fig. 4 of this Article, the y axes in panels ‘b–e’ are incorrect. The correct version of Fig. 4 appears below as Fig. 1.
Independent effect of prior exacerbation frequency and disease severity on the risk of future exacerbations of COPD: a retrospective cohort study
Authors: Margüello Miguel Santibañez , Garrastazu Roberto , Ruiz-Nuñez Mario , Helguera Jose Manuel , Arenal Sandra , Bonnardeux Cristina , León Carlos , Miravitlles Marc , García-Rivero Juan Luis
Published: September 2016

Few studies have researched the independent effect of COPD severity on the risk of future exacerbations adjusted by previous exacerbation frequency. We aimed to analyse the independent effect of COPD severity on the risk of exacerbations in the following year, and whether this effect was stronger or not than the effect of a previous history of exacerbations. We conducted a retrospective population-based cohort study including 900 patients with confirmed COPD. Exacerbation frequency was observed for the previous year and for the following year. Patients were defined as ‘Frequent Exacerbator’ (FE) phenotype if they suffered ⩾2 exacerbations in a year, and were categorised according to the severity of COPD (GOLD Grades 1–4). Odds ratios (ORs) were estimated by logistic regression adjusting for age, gender, smoking status, severity of COPD and being FE in the previous year. The main predictor of being FE among all grades of COPD severity was a history of frequent exacerbations in the previous year: adjusted OR 4.97; 95% confidence interval (CI) (3.54–6.97). COPD severity was associated with a higher risk of being FE: Crude OR GOLD Grade 4 3.86; 95% CI (1.50–9.93). However, this association diminished after adjusting for being FE in the previous year: adjusted OR 2.08; 95% CI (0.75–5.82). Our results support that a history of frequent exacerbations in the previous year is the most important independent predictor of exacerbations in the following year, also among the most severe COPD patients. Severity of COPD would be associated with a higher risk of exacerbations, but this effect would be partly determined by the exacerbations suffered in the previous year.
Screening of SOD1, FUS and TARDBP genes in patients with amyotrophic lateral sclerosis in central-southern China
Authors: Hou Lihua , Jiao Bin , Xiao Tingting , Zhou Lu , Zhou Zhifan , Du Juan , Yan Xinxiang , Wang Junling , Tang Beisha , Shen Lu
Published: September 2016

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons of the brain, brainstem and spinal cord. To date, mutations in more than 30 genes have been linked to the pathogenesis of ALS. Among them, SOD1, FUS and TARDBP are ranked as the three most common genes associated with ALS. However, no mutation analysis has been reported in central-southern China. In this study, we sequenced SOD1, FUS and TARDBP in a central-southern Chinese cohort of 173 patients with ALS (15 familial ALS and 158 sporadic ALS) to detect mutations. As a result, five missense mutations in SOD1, namely, p.D101N, p.D101G, p.C111Y, p.N86S and p.V87A, were identified in three unrelated familial probands and three sporadic cases; two mutations in FUS were found in two unrelated familial probands, including an insertion mutation (p.P525_Y526insY) and a missense mutation (p.R521H); no variants of TARDBP were observed in patients. Therefore, SOD1 mutations were present in 20.0% of familial ALS patients and 1.9% of sporadic ALS patients, while FUS mutations were responsible for 13.3% of familial ALS cases and TARDBP mutations were rare in either familial or sporadic ALS cases. This study broadens the known mutational spectrum in patients with ALS and further demonstrates the necessity for genetic screening in ALS patients from central-southern China.
Glucose-dependent anaplerosis in cancer cells is required for cellular redox balance in the absence of glutamine
Authors: Cetinbas Naniye Mallı , Sudderth Jessica , Harris Robert C. , Cebeci Aysun , Negri Gian L. , Yılmaz Ömer H. , DeBerardinis Ralph J. , Sorensen Poul H.
Published: September 2016

Cancer cells have altered metabolism compared to normal cells, including dependence on glutamine (GLN) for survival, known as GLN addiction. However, some cancer cell lines do not require GLN for survival and the basis for this discrepancy is not well understood. GLN is a precursor for antioxidants such as glutathione (GSH) and NADPH, and GLN deprivation is therefore predicted to deplete antioxidants and increase reactive oxygen species (ROS). Using diverse human cancer cell lines we show that this occurs only in cells that rely on GLN for survival. Thus, the preference for GLN as a dominant antioxidant source defines GLN addiction. We show that despite increased glucose uptake, GLN addicted cells do not metabolize glucose via the TCA cycle when GLN is depleted, as revealed by 13C-glucose labeling. In contrast, GLN independent cells can compensate by diverting glucose-derived pyruvate into the TCA cycle. GLN addicted cells exhibit reduced PDH activity, increased PDK1 expression, and PDK inhibition partially rescues GLN starvation-induced ROS and cell death. Finally, we show that combining GLN starvation with pro-oxidants selectively kills GLN addicted cells. These data highlight a major role for GLN in maintaining redox balance in cancer cells that lack glucose-dependent anaplerosis.
Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo
Authors: Greening David W. , Ji Hong , Chen Maoshan , Robinson Bruce W. S. , Dick Ian M. , Creaney Jenette , Simpson Richard J.
Published: September 2016

Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.
Synthesis of semicrystalline nanocapsular structures obtained by Thermally Induced Phase Separation in nanoconfinement
Authors: Torino Enza , Aruta Rosaria , Sibillano Teresa , Giannini Cinzia , Netti Paolo A.
Published: September 2016

Phase separation of a polymer solution exhibits a peculiar behavior when induced in a nanoconfinement. The energetic constraints introduce additional interactions between the polymer segments that reduce the number of available configurations. In our work, this effect is exploited in a one-step strategy called nanoconfined-Thermally Induced Phase Separation (nc-TIPS) to promote the crystallization of polymer chains into nanocapsular structures of controlled size and shell thickness. This is accomplished by performing a quench step of a low-concentrated PLLA-dioxane-water solution included in emulsions of mean droplet size <500 nm acting as nanodomains. The control of nanoconfinement conditions enables not only the production of nanocapsules with a minimum mean particle diameter of 70 nm but also the tunability of shell thickness and its crystallinity degree. The specific properties of the developed nanocapsular architectures have important implications on release mechanism and loading capability of hydrophilic and lipophilic payload compounds.
Automatic Construction of Predictive Neuron Models through Large Scale Assimilation of Electrophysiological Data
Authors: Nogaret Alain , Meliza C. Daniel , Margoliash Daniel , Abarbanel Henry D. I.
Published: September 2016

We report on the construction of neuron models by assimilating electrophysiological data with large-scale constrained nonlinear optimization. The method implements interior point line parameter search to determine parameters from the responses to intracellular current injections of zebra finch HVC neurons. We incorporated these parameters into a nine ionic channel conductance model to obtain completed models which we then use to predict the state of the neuron under arbitrary current stimulation. Each model was validated by successfully predicting the dynamics of the membrane potential induced by 20–50 different current protocols. The dispersion of parameters extracted from different assimilation windows was studied. Differences in constraints from current protocols, stochastic variability in neuron output, and noise behave as a residual temperature which broadens the global minimum of the objective function to an ellipsoid domain whose principal axes follow an exponentially decaying distribution. The maximum likelihood expectation of extracted parameters was found to provide an excellent approximation of the global minimum and yields highly consistent kinetics for both neurons studied. Large scale assimilation absorbs the intrinsic variability of electrophysiological data over wide assimilation windows. It builds models in an automatic manner treating all data as equal quantities and requiring minimal additional insight.
Multiple intrinsic factors act in concert with Lhx2 to direct retinal gliogenesis
Authors: de Melo Jimmy , Clark Brian S. , Blackshaw Seth
Published: September 2016

Müller glia (MG) are the principal glial cell type in the vertebrate retina. Recent work has identified the LIM homeodomain factor encoding gene Lhx2 as necessary for both Notch signaling and MG differentiation in late-stage retinal progenitor cells (RPCs). However, the extent to which Lhx2 interacts with other intrinsic regulators of MG differentiation is unclear. We investigated this question by investigating the effects of overexpression of multiple transcriptional regulators that are either known or hypothesized to control MG formation, in both wildtype and Lhx2-deficient RPCs. We observe that constitutively elevated Notch signaling, induced by N1ICD electroporation, inhibited gliogenesis in wildtype animals, but rescued MG development in Lhx2-deficient retinas. Electroporation of Nfia promoted the formation of cells with MG-like radial morphology, but did not drive expression of MG molecular markers. Plagl1 and Sox9 did not induce gliogenesis in wildtype animals, but nonetheless activated expression of the Müller marker P27Kip1 in Lhx2-deficient cells. Finally, Sox2, Sox8, and Sox9 promoted amacrine cell formation in Lhx2-deficient cells, but not in wildtype retinas. These findings demonstrate that overexpression of individual gliogenic factors typically regulates only a subset of characteristic MG markers, and that these effects are differentially modulated by Lhx2.
Quantifying the pharmacology of antimalarial drug combination therapy
Authors: Hastings Ian M. , Hodel Eva Maria , Kay Katherine
Published: September 2016

Most current antimalarial drugs are combinations of an artemisinin plus a ‘partner’ drug from another class, and are known as artemisinin-based combination therapies (ACTs). They are the frontline drugs in treating human malaria infections. They also have a public-health role as an essential component of recent, comprehensive scale-ups of malaria interventions and containment efforts conceived as part of longer term malaria elimination efforts. Recent reports that resistance has arisen to artemisinins has caused considerable concern. We investigate the likely impact of artemisinin resistance by quantifying the contribution artemisinins make to the overall therapeutic capacity of ACTs. We achieve this using a simple, easily understood, algebraic approach and by more sophisticated pharmacokinetic/pharmacodynamic analyses of drug action; the two approaches gave consistent results. Surprisingly, the artemisinin component typically makes a negligible contribution (≪0.0001%) to the therapeutic capacity of the most widely used ACTs and only starts to make a significant contribution to therapeutic outcome once resistance has started to evolve to the partner drugs. The main threat to antimalarial drug effectiveness and control comes from resistance evolving to the partner drugs. We therefore argue that public health policies be re-focussed to maximise the likely long-term effectiveness of the partner drugs.
Assessing morphology and function of the semicircular duct system: introducing new in-situ visualization and software toolbox
Authors: David R. , Stoessel A. , Berthoz A. , Spoor F. , Bennequin D.
Published: September 2016

The semicircular duct system is part of the sensory organ of balance and essential for navigation and spatial awareness in vertebrates. Its function in detecting head rotations has been modelled with increasing sophistication, but the biomechanics of actual semicircular duct systems has rarely been analyzed, foremost because the fragile membranous structures in the inner ear are hard to visualize undistorted and in full. Here we present a new, easy-to-apply and non-invasive method for three-dimensionalin-situvisualization and quantification of the semicircular duct system, using X-ray micro tomography and tissue staining with phosphotungstic acid. Moreover, we introduce Ariadne, a software toolbox which provides comprehensive and improved morphological and functional analysis of any visualized duct system. We demonstrate the potential of these methods by presenting results for the duct system of humans, the squirrel monkey and the rhesus macaque, making comparisons with past results from neurophysiological, oculometric and biomechanical studies. Ariadne is freely available athttp://www.earbank.org.
Alterations of mitochondrial dynamics allow retrograde propagation of locally initiated axonal insults
Authors: Lassus Benjamin , Magnifico Sebastien , Pignon Sandra , Belenguer Pascale , Miquel Marie-Christine , Peyrin Jean-Michel
Published: September 2016

In chronic neurodegenerative syndromes, neurons progressively die through a generalized retraction pattern triggering retrograde axonal degeneration toward the cell bodies, which molecular mechanisms remain elusive. Recent observations suggest that direct activation of pro-apoptotic signaling in axons triggers local degenerative events associated with early alteration of axonal mitochondrial dynamics. This raises the question of the role of mitochondrial dynamics on both axonal vulnerability stress and their implication in the spreading of damages toward unchallenged parts of the neuron. Here, using microfluidic chambers, we assessed the consequences of interfering with OPA1 and DRP1 proteins on axonal degeneration induced by local application of rotenone. We found that pharmacological inhibition of mitochondrial fission prevented axonal damage induced by rotenone, in low glucose conditions. While alteration of mitochondrial dynamics per se did not lead to spontaneous axonal degeneration, it dramatically enhanced axonal vulnerability to rotenone, which had no effect in normal glucose conditions, and promoted retrograde spreading of axonal degeneration toward the cell body. Altogether, our results suggest a mitochondrial priming effect in axons as a key process of axonal degeneration. In the context of neurodegenerative diseases, like Parkinson’s and Alzheimer’s, mitochondria fragmentation could hasten neuronal death and initiate spatial dispersion of locally induced degenerative events.
Genome-wide Identification of TCP Family Transcription Factors from Populus euphratica and Their Involvement in Leaf Shape Regulation
Authors: Ma Xiaodong , Ma Jianchao , Fan Di , Li Chaofeng , Jiang Yuanzhong , Luo Keming
Published: September 2016

Higher plants have been shown to experience a juvenile vegetative phase, an adult vegetative phase, and a reproductive phase during its postembryonic development and distinct lateral organ morphologies have been observed at the different development stages. Populus euphratica, commonly known as a desert poplar, has developed heteromorphic leaves during its development. The TCP family genes encode a group of plant-specific transcription factors involved in several aspects of plant development. In particular, TCPs have been shown to influence leaf size and shape in many herbaceous plants. However, whether these functions are conserved in woody plants remains unknown. In the present study, we carried out genome-wide identification of TCP genes in P. euphratica and P. trichocarpa, and 33 and 36 genes encoding putative TCP proteins were found, respectively. Phylogenetic analysis of the poplar TCPs together with Arabidopsis TCPs indicated a biased expansion of the TCP gene family via segmental duplications. In addition, our results have also shown a correlation between different expression patterns of several P. euphratica TCP genes and leaf shape variations, indicating their involvement in the regulation of leaf shape development.