bluuebunny/crossref_metadata_2025 huggingface dataset:
NINE SLOUGHS: PROFILING THE CLIMATE HISTORY OF THE YUAN AND MING DYNASTIES, 1260–1644†
Authors: Brook Timothy
Published: November 2016

I have written this essay to address what I regard as a pressing need among China historians for a stronger model of climate change and its impact on state and society during the imperial period. We have all become acutely conscious of climate change as an element of our own world, yet few of us have considered the impact of climate, particularly climate change, on our subjects of study. China is not without its climate historians, and yet the collective research is still in an early phase. Aware of this problem for some time, I published preliminary findings in the form of a chronological profile of climate anomalies through the Yuan and Ming dynasties in 2010. Burying my findings in a textbook has meant that the periodization offered there has captured the interest of some students but gone largely ignored by scholars in the field. Since then I have done further research and have revised some of those findings, and would now like to offer a fuller presentation of methods and findings.
RECENT STUDIES OF WARTIME CHINA
Authors: Esherick Joseph
Published: November 2016

The history of World War II has long been a favorite topic of military, diplomatic, and social historians (even more so for viewers of the History Channel), but the focus has typically been on the European theater. With a more limited archival record, the conflict in Asia has received less attention. This is certainly not because Asia was less important. The war undermined the legitimacy of colonial regimes throughout Southeast Asia, led to the division of Korea into two hostile states, and contributed in fundamental ways to the collapse of the Nationalist regime in China and the triumph of the Communist revolution. The last few years have seen substantial new scholarship on the 1937–45 War of Resistance in China and what Japanese historians often call the Fifteen-Year War, starting with the occupation of Manchuria in 1931. The number of titles falls far short of what has been written on Europe, but the war in China is now being approached in new and interesting ways.
Smoking Cessation Care for People with a Mental Illness: Family Carer Expectations of Health and Community Services
Authors: Bailey Jacqueline M. , Wye Paula M. , Stockings Emily A. , Bartlem Kate M. , Metse Alexandra P. , Wiggers John H. , Bowman Jennifer A.
Published: November 2016

Introduction: Smoking prevalence remains high among people with a mental illness, contributing to higher levels of morbidity and mortality. Health and community services are an opportune setting for the provision of smoking cessation care. Although family carers are acknowledged to play a critical role in supporting the care and assistance provided by such services to people with a mental illness, their expectations regarding the delivery of smoking cessation care have not been examined.

Aims: To explore family carer expectations of smoking cessation care provision by four types of health services, to clients with a mental illness, and factors associated with expectations.

Methods: A cross-sectional survey was conducted with carers of a person with a mental illness residing in New South Wales, Australia. Carers were surveyed regarding their expectations of smoking cessation care provision from four types of health services. Possible associations between carer expectation of smoking cessation care provision and socio-demographic and attitudinal variables were explored.

Results: Of 144 carers, the majority of carers considered that smoking cessation care should be provided by: mental health hospitals (71.4%), community mental health services (78.0%), general practice (82.7%), and non-government organisations (56.6%). The factor most consistently related to expectation of care was a belief that smoking cessation could positively impact mental health.

Conclusions: The majority of carers expected smoking cessation treatment to be provided by all services catering for people with a mental illness, reinforcing the appropriateness for such services to provide smoking cessation care for clients in an effective and systematic manner.
Anti-icon icon: Gabriele Basilico’s photography of the Italian urban landscape
Authors: Tommasini Alexandra
Published: November 2016

This article explores Gabriele Basilico’s photographs of the contemporary Italian environment and argues for their status as both iconic – that is to say, distinctive, highly visible, and memorable – and anti-iconic symbols or images. The discussion first explores the anti-iconic impulse in Basilico’s work. It marks out his standing as one of the most prominent proponents of the trend in contemporary Italian photography which sought to counter the mythic view of the country’s landscape and highlights his involvement in the trend’s seminal exhibition, Viaggio in Italia (1984). The article then makes a case for the simultaneous iconic nature of Basilico’s photographs by looking at the 2007/08 exhibition Milano si mostra. 1 Km con Gabriele Basilico, examining the ways in which Basilico’s images were made into icons of Milan’s urban identity.
Mathematical subtleties and scientific knowledge: Francis Bacon and mathematics, at the crossing of two traditions
Authors: MORI GIULIANO
Published: November 2016

This article engages the much-debated role of mathematics in Bacon's philosophy and inductive method at large. The many references to mathematics in Bacon's works are considered in the context of the humanist reform of thecurriculum studiorumand, in particular, through a comparison with the kinds of natural and intellectual subtlety as they are defined by many sixteenth-century authors, including Cardano, Scaliger and Montaigne. Additionally, this article gives a nuanced background to the ‘subtlety’ commonly thought to have been eschewed by Bacon and by Bacon's self-proclaimed followers in the Royal Society of London. The aim of this article is ultimately to demonstrate that Bacon did not reject the use of mathematics in natural philosophy altogether. Instead, he hoped that following theGreat Instaurationa kind of non-abstract mathematics could be founded: a kind of mathematics which was to serve natural philosophy by enabling men to grasp the intrinsic subtlety of nature. Rather than mathematizing nature, it was mathematics that needed to be ‘naturalized’.
Between-individual variation in nematode burden among juveniles in a wild host
Authors: GRANROTH-WILDING H. M. V. , DAUNT F. , CUNNINGHAM E. J. A. , BURTHE S. J.
Published: November 2016

Parasite infection in young animals can affect host traits related to demographic processes such as survival and reproduction, and is therefore crucial to population viability. However, variation in infection among juvenile hosts is poorly understood. Experimental studies have indicated that effects of parasitism can vary with host sex, hatching order and hatch date, yet it remains unclear whether this is linked to differences in parasite burdens. We quantified gastrointestinal nematode burdens of wild juvenile European shags (Phalacrocorax aristotelis) using twoin situmeasures (endoscopy of live birds and necropsy of birds that died naturally) and one non-invasive proxy measure (fecal egg counts (FECs)).In situmethods revealed that almost all chicks were infected (98%), that infections established at an early age and that older chicks hosted more worms, but FECs underestimated prevalence. We found no strong evidence that burdens differed with host sex, rank or hatch date. Heavier chicks had higher burdens, demonstrating that the relationship between burdens and their costs is not straightforward.In situmeasures of infection are therefore a valuable tool in building our understanding of the role that parasites play in the dynamics of structured natural populations.
Educational achievement in psychiatric patients and their siblings: a register-based study in 30 000 individuals in The Netherlands
Authors: Tempelaar W. M. , Termorshuizen F. , MacCabe J. H. , Boks M. P. M. , Kahn R. S.
Published: November 2016

Background

Poor educational achievement is associated with a range of psychiatric disorders. Several studies suggest that this underperformance is due to cognitive deficits that commence before disease onset and reflect a genetic risk for this disorder. However, the specificity and the familial contribution of this cognitive deficit are not clear. We analysed lifetime educational achievement of psychiatric patients diagnosed with schizophrenia, bipolar or depressive disorder and their unaffected siblings.

Method

In a register-based case-control study, 1561 patients with schizophrenia, 813 patients with bipolar disorder, 8112 patients with depression, and their siblings were each matched with eight population controls. Patients, siblings and controls were compared on the highest educational stream they completed.

Results

Lower educational achievement was present in schizophrenia patients from primary school onwards [completing primary school: odds ratio (OR) 0.69; completing secondary school: OR 0.69; completing academic education: OR 0.46], compared to patients with bipolar disorder or depression. Siblings of schizophrenia, bipolar or depressed patients showed no underachievement at primary or secondary school, but siblings of schizophrenia patients as well as siblings of depressed patients were less successful in their educational achievement after secondary school (completing academic education, schizophrenia siblings: OR 0.90; depressive disorder siblings: OR 0.91).

Conclusions

Educational underachievement from primary school onwards is specifically related to schizophrenia and not to bipolar disorder or depression. Moreover, it appears to be a harbinger of the illness, since it is not found in their siblings. These results add to evidence that early cognitive deficits are a distinct feature of the schizophrenia phenotype.
Institutional and socio-economic drivers of work-to-retirement trajectories in the Netherlands
Authors: RIEKHOFF AART-JAN
Published: November 2016

Institutional exit pathways shape individual trajectories from work to retirement. In the Netherlands, early retirement schemes as well as disability and unemployment benefits structure the timing and complexity of transitions within such trajectories. Simultaneously, access to these exit pathways depends on the individuals’ entitlements to various social security programmes as well as their freedom to decide on the timing and path of exit. In this study, sequence analysis was applied to register data of primary sources of income with the aim of identifying the main trajectories from work to retirement between the ages of 56 and 66 for a sample of Dutch men and women born between 1943 and 1945 (N = 2,277). Seven distinct trajectories were found: ‘early retirement’, ‘premature retirement’, ‘late retirement’, ‘disability’, ‘unemployment’, ‘inactivity’ and ‘drop-out’. Multinomial logistic regression analysis was applied to investigate the relations of these trajectories with a set of individual and socio-economic characteristics, as well as factors at a firm level. Especially women, non-natives, the lower educated and the self-employed were found to have a greater risk of ending up in the ‘involuntary’ trajectories of late retirement, disability, unemployment and inactivity. Public-sector employees, farmers and craftsmen, and skilled blue-collar workers were less likely to differentiate from the norm of entering into premature retirement between the ages of 60 and 64.
Adding low-cost passive toe joints to the feet structure of SURENA III humanoid robot
Authors: Sadedel Majid , Yousefi-Koma Aghil , Khadiv Majid , Mahdavian Mohhamad
Published: November 2016

Adding active toe joints to a humanoid robot structure has lots of difficulties such as mounting a small motor and an encoder on the robot feet. Conversely, adding passive toe joints is simple, since it only consists of a spring and a damper. Due to lots of benefits of implementing passive toe joints, mentioned in the literature, the goal of this study is to add passive toe joints to the SURENA III humanoid robot which was designed and fabricated at the Center of Advanced Systems and Technologies (CAST), University of Tehran. To this end, a simple passive toe joint is designed and fabricated, at first. Then, stiffness and damping coefficients are calculated using a vision-based measurement. Afterwards, a gait planning routine for humanoid robots equipped with passive toe joints is implemented. The tip-over stability of the gait is studied, considering the vibration of the passive toe joints in swing phases. The multi-body dynamics of the robot equipped with passive toe joints are presented using the Lagrange approach. Furthermore, system identification routine is adopted to model the dynamic behaviors of the power transmission system. By adding the calculated actuating torques for these two models, the whole dynamic model of the robot is computed. Finally, the performance of the proposed approach is evaluated by several simulations and experimental results. Results show that using passive toe joints reduces energy consumption of ankle and knee joints by 15.3% and 9.0%, respectively. Moreover, with relatively large values of stiffness coefficients, the required torque and power of the knee and hip joints during heel-off motion reduces as the ankle joint torque and power increases.
Patterns of virulence factor expression and antimicrobial resistance in Achromobacter xylosoxidans and Achromobacter ruhlandii isolates from patients with cystic fibrosis
Authors: PEREIRA R. H. V. , LEÃO R. S. , CARVALHO-ASSEF A. P. , ALBANO R. M. , RODRIGUES E. R. A. , FIRMIDA M. C. , FOLESCU T. W. , PLOTKOWSKI M. C. , BERNARDO V. G. , MARQUES E. A.
Published: November 2016

Achromobacter spp. are opportunistic pathogens increasingly recovered from adult patients with cystic fibrosis (CF). We report the characterization of 122 Achromobacter spp. isolates recovered from 39 CF patients by multilocus sequence typing, virulence traits, and susceptibility to antimicrobials. Two species, A. xylosoxidans (77%) and A. ruhlandii (23%) were identified. All isolates showed a similar biofilm formation ability, and a positive swimming phenotype. By contrast, 4·3% and 44·4% of A. xylosoxidans and A. ruhlandii, respectively, exhibited a negative swarming phenotype, making the swimming and swarming abilities of A. xylosoxidans significantly higher than those of A. ruhlandii. A. xylosoxidans isolates from an outbreak clone also exhibited significantly higher motility. Both species were generally susceptible to ceftazidime, ciprofloxacin, imipenem and trimethoprim/sulphamethoxazole and there was no significant difference in susceptibility between isolates from chronic or sporadic infection. However, A. xylosoxidans isolates from chronic and sporadic cases were significantly more resistant to imipenem and ceftazidime than isolates of the outbreak clone.
POLITICS AND THE CASE OF POETRY: ARENDT ON BRECHT
Authors: MARKELL PATCHEN
Published: November 2016

Hannah Arendt's essay on Bertolt Brecht has often been understood as an indictment of Brecht's postwar accommodation with the Stalinist regime in East Germany, in line with Arendt's supposed commitment to a firm separation between poetry and politics. Offering the first full reconstruction of the transnational history of Arendt's writing on Brecht, this article shows instead that Arendt's essay was a defense of Brecht against the polemics it is often taken to exemplify. Joining poetry to politics by holding both at a distance from philosophy, Arendt assigned poetry the vocation of disruptive faithfulness to factual reality, which allowed her to praise Brecht on political grounds and to leverage forbearance for his political “sins.” Indeed, by narrating Brecht's “sins” and “punishment” against the grain of Cold War discourse about the poet, Arendt's essay emulated aspects of the poetic practice she admired in Brecht's writing.
Stressbezogene Korrelate von Angst und Depression bei Mädchen mit chronischen Kopfschmerzen
Authors: Bung Simone , Saile Helmut , Laessle Reinhold
Published: November 2016

Zusammenfassung. Chronische Kopfschmerzen bei Kindern und Jugendlichen sind ein häufiges Krankheitsbild, das bei vielen Betroffenen mit Angst und Depressivität einhergeht. In der vorliegenden Studie wurde überprüft, inwieweit die psychische und physische Stressbelastung das Auftreten von Depressivität und Angst beeinflusst und welche Rolle die Stressbewältigungsstrategien der Kinder spielen. Es wurden 77 15-jährige Mädchen mit chronischen Kopfschmerzen untersucht, bei denen die Stressbelastung und Stressverarbeitung mit dem Fragebogen zur Erhebung von Stress und Stressbewältigung im Kindes- und Jugendalter gemessen wurde, die Depressivität mit dem Depressionsinventar für Kinder und Jugendliche, die Angst mit der deutschen Version des State-Trait Anxiety Inventory for Children. Mit Regressionsanalysen wurden Zusammenhänge zwischen Stressfaktoren und Depressivität bzw. Angst überprüft. Bei den hier untersuchten jungen Mädchen waren körperlich erlebte Stresssymptome mit einer erhöhten Angst verbunden. Dies gilt auch unter Berücksichtigung der vorhandenen psychischen Stressbelastung und der generellen Empfindlichkeit für Stressoren. Hingegen waren die körperlich erlebten Stresssymptome nicht signifikant mit einer erhöhten Depressivität korreliert. Hier erwiesen sich als wichtigste Prädiktoren die psychische Stressbelastung und die Stressvulnerabilität. Die mit Depressivität und Angst einhergehende physische und psychische Stresssymptomatik kann von den Kindern mit Kopfschmerzen nicht adäquat kompensiert werden, da sowohl Angst als auch Depressivität mit stressverstärkenden Copingstrategien verbunden sind. Die Ergebnisse sprechen für eine Fokussierung der Wahrnehmung auf körperlicher Stresssymptome bei ängstlichen Kopfschmerzkindern und für eine Vermeidung dieser Wahrnehmung bei Kopfschmerzkindern mit ausgeprägter Depressivität.
The GCN5-CITED2-PKA signalling module controls hepatic glucose metabolism through a cAMP-induced substrate switch
Authors: Sakai Mashito , Tujimura-Hayakawa Tomoko , Yagi Takashi , Yano Hiroyuki , Mitsushima Masaru , Unoki-Kubota Hiroyuki , Kaburagi Yasushi , Inoue Hiroshi , Kido Yoshiaki , Kasuga Masato , Matsumoto Michihiro
Published: November 2016

Hepatic gluconeogenesis during fasting results from gluconeogenic gene activation via the glucagon–cAMP–protein kinase A (PKA) pathway, a process whose dysregulation underlies fasting hyperglycemia in diabetes. Such transcriptional activation requires epigenetic changes at promoters by mechanisms that have remained unclear. Here we show that GCN5 functions both as a histone acetyltransferase (HAT) to activate fasting gluconeogenesis and as an acetyltransferase for the transcriptional co-activator PGC-1α to inhibit gluconeogenesis in the fed state. During fasting, PKA phosphorylates GCN5 in a manner dependent on the transcriptional coregulator CITED2, thereby increasing its acetyltransferase activity for histone and attenuating that for PGC-1α. This substrate switch concomitantly promotes both epigenetic changes associated with transcriptional activation and PGC-1α–mediated coactivation, thereby triggering gluconeogenesis. The GCN5-CITED2-PKA signalling module and associated GCN5 substrate switch thus serve as a key driver of gluconeogenesis. Disruption of this module ameliorates hyperglycemia in obese diabetic animals, offering a potential therapeutic strategy for such conditions.
Secondary migration and leakage of methane from a major tight-gas system
Authors: Wood James M. , Sanei Hamed
Published: November 2016

Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere.
Correction: Corrigendum: Regulation of PERK–eIF2α signalling by tuberous sclerosis complex-1 controls homoeostasis and survival of myelinating oligodendrocytes
Authors: Jiang Minqing , Liu Lei , He Xuelian , Wang Haibo , Lin Wensheng , Wang Huimin , Yoon Sung O , Wood Teresa L , Lu Q. Richard
Published: November 2016

Nature Communications 7: Article number: 12185 (2016); Published: 15 July 2016; Updated: 22 November 2016 The GEO accession number provided in this article is incorrect; the correct number is GSE74893.
Correction: Corrigendum: Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity
Authors: Schöne Stefanie , Jurk Marcel , Helabad Mahdi Bagherpoor , Dror Iris , Lebars Isabelle , Kieffer Bruno , Imhof Petra , Rohs Remo , Vingron Martin , Thomas-Chollier Morgane , Meijsing Sebastiaan H.
Published: November 2016

Nature Communications 7: Article number: 12621 (2016); Published: 1 September 2016; Updated: 22 November 2016 The financial support for this Article was not fully acknowledged. The Acknowledgements should have included the following: M.B.H. and P.I. are grateful for computational resources provided by the North-German Supercomputing Alliance and the ZEDAT cluster Soroban of the Freie Universität Berlin.
Perceptual learning in a non-human primate model of artificial vision
Authors: Killian Nathaniel J. , Vurro Milena , Keith Sarah B. , Kyada Margee J. , Pezaris John S.
Published: November 2016

Visual perceptual grouping, the process of forming global percepts from discrete elements, is experience-dependent. Here we show that the learning time course in an animal model of artificial vision is predicted primarily from the density of visual elements. Three naïve adult non-human primates were tasked with recognizing the letters of the Roman alphabet presented at variable size and visualized through patterns of discrete visual elements, specifically, simulated phosphenes mimicking a thalamic visual prosthesis. The animals viewed a spatially static letter using a gaze-contingent pattern and then chose, by gaze fixation, between a matching letter and a non-matching distractor. Months of learning were required for the animals to recognize letters using simulated phosphene vision. Learning rates increased in proportion to the mean density of the phosphenes in each pattern. Furthermore, skill acquisition transferred from trained to untrained patterns, not depending on the precise retinal layout of the simulated phosphenes. Taken together, the findings suggest that learning of perceptual grouping in a gaze-contingent visual prosthesis can be described simply by the density of visual activation.
Mitochondrial growth during the cell cycle of Trypanosoma brucei bloodstream forms
Authors: Jakob Martin , Hoffmann Anneliese , Amodeo Simona , Peitsch Camille , Zuber Benoît , Ochsenreiter Torsten
Published: November 2016

Mitochondrial organelles need to be replicated during cell division. Many aspects of this process have been studied in great detail, however the actual size increase and the position of organelle growth are less well understood. We use the protozoan parasite Trypanosoma brucei that contains a single mitochondrion to study organelle biogenesis by fluorescence microscopy. From the analysis of more than 1000 T. brucei bloodstream form cells of a nonsynchronous population we conclude that the mitochondrial network mostly grows from two areas along the main organelle axis, posterior and anterior of the nucleus. Loops and branches from these two areas eventually fuse to build a complex network. Together with the appearance of the division fold in the posterior part of the cell, pruning of the mitochondrial network and finally separation into the two daughter cells occurs. Overall organelle biogenesis is not continuous during cell growth and occurs mostly in the last part of the cell cycle. Furthermore, using 3D STED super resolution microscopy we reconstruct the volume of the organelle and characterize the region where the mitochondrial genome is positioned by serial block face scanning electron microscopy.
New Fluoride-arsenide Diluted Magnetic Semiconductor (Ba,K)F(Zn,Mn)As with Independent Spin and Charge Doping
Authors: Chen Bijuan , Deng Zheng , Li Wenmin , Gao Moran , Liu Qingqing , Gu C. Z. , Hu F. X. , Shen B. G. , Frandsen Benjamin , Cheung Sky , Lian Liu , Uemura Yasutomo J. , Ding Cui , Guo Shengli , Ning Fanlong , Munsie Timothy J. S. , Wilson Murray Neff , Cai Yipeng , Luke Graeme , Guguchia Zurab , Yonezawa Shingo , Li Zhi , Jin Changqing
Published: November 2016

We report the discovery of a new fluoride-arsenide bulk diluted magnetic semiconductor (Ba,K)F(Zn,Mn)As with the tetragonal ZrCuSiAs-type structure which is identical to that of the “1111” iron-based superconductors. The joint hole doping via (Ba,K) substitution & spin doping via (Zn,Mn) substitution results in ferromagnetic order with Curie temperature up to 30 K and demonstrates that the ferromagnetic interactions between the localized spins are mediated by the carriers. Muon spin relaxation measurements confirm the intrinsic nature of the long range magnetic order in the entire volume in the ferromagnetic phase. This is the first time that a diluted magnetic semiconductor with decoupled spin and charge doping is achieved in a fluoride compound. Comparing to the isostructure oxide counterpart of LaOZnSb, the fluoride DMS (Ba,K)F(Zn,Mn)As shows much improved semiconductive behavior that would be benefit for further application developments.
Long-range synchrony and emergence of neural reentry
Authors: Keren Hanna , Marom Shimon
Published: November 2016

Neural synchronization across long distances is a functionally important phenomenon in health and disease. In order to access the basis of different modes of long-range synchrony, we monitor spiking activities over centimetre scale in cortical networks and show that the mode of synchrony depends upon a length scale, λ, which is the minimal path that activity should propagate through to find its point of origin ready for reactivation. When λ is larger than the physical dimension of the network, distant neuronal populations operate synchronously, giving rise to irregularly occurring network-wide events that last hundreds of milliseconds to several seconds. In contrast, when λ approaches the dimension of the network, a continuous self-sustained reentry propagation emerges, a regular seizure-like mode that is marked by precise spatiotemporal patterns (‘synfire chains’) and may last many minutes. Termination of a reentry phase is preceded by a decrease of propagation speed to a halt. Stimulation decreases both propagation speed and λ values, which modifies the synchrony mode respectively. The results contribute to the understanding of the origin and termination of different modes of neural synchrony as well as their long-range spatial patterns, while hopefully catering to manipulation of the phenomena in pathological conditions.
Body height as risk factor for emphysema in COPD
Authors: Miniati Massimo , Bottai Matteo , Pavlickova Ivana , Monti Simonetta
Published: November 2016

Pulmonary emphysema is a phenotypic component of chronic obstructive pulmonary disease (COPD) which carries substantial morbidity and mortality. We explored the association between emphysema and body height in 726 patients with COPD using computed tomography as the reference diagnostic standard for emphysema. We applied univariate analysis to look for differences between patients with emphysema and those without, and multivariate logistic regression to identify significant predictors of the risk of emphysema. As covariates we included age, sex, body height, body mass index, pack-years of smoking, and forced expiratory volume in one second (FEV1) as percent predicted. The overall prevalence of emphysema was 52%. Emphysemic patients were significantly taller and thinner than non-emphysemic ones, and featured significantly higher pack-years of smoking and lower FEV1(P < 0.001). The prevalence of emphysema rose linearly by 10-cm increase in body height (r2 = 0.96). In multivariate analysis, the odds of emphysema increased by 5% (95% confidence interval, 3 to 7%) along with one-centimeter increase in body height, and remained unchanged after adjusting for all the potential confounders considered (P < 0.001). The odds of emphysema were not statistically different between males and females. In conclusion, body height is a strong, independent risk factor for emphysema in COPD.
Use of Zebrafish Larvae as a Multi-Endpoint Platform to Characterize the Toxicity Profile of Silica Nanoparticles
Authors: Pham Duc-Hung , De Roo Bert , Nguyen Xuan-Bac , Vervaele Mattias , Kecskés Angela , Ny Annelii , Copmans Daniëlle , Vriens Hanne , Locquet Jean-Pierre , Hoet Peter , de Witte Peter A. M.
Published: November 2016

Nanomaterials are being extensively produced and applied in society. Human and environmental exposures are, therefore, inevitable and so increased attention is being given to nanotoxicity. While silica nanoparticles (NP) are one of the top five nanomaterials found in consumer and biomedical products, their toxicity profile is poorly characterized. In this study, we investigated the toxicity of silica nanoparticles with diameters 20, 50 and 80 nm using an in vivo zebrafish platform that analyzes multiple endpoints related to developmental, cardio-, hepato-, and neurotoxicity. Results show that except for an acceleration in hatching time and alterations in the behavior of zebrafish embryos/larvae, silica NPs did not elicit any developmental defects, nor any cardio- and hepatotoxicity. The behavioral alterations were consistent for both embryonic photomotor and larval locomotor response and were dependent on the concentration and the size of silica NPs. As embryos and larvae exhibited a normal touch response and early hatching did not affect larval locomotor response, the behavior changes observed are most likely the consequence of modified neuroactivity. Overall, our results suggest that silica NPs do not cause any developmental, cardio- or hepatotoxicity, but they pose a potential risk for the neurobehavioral system.
Development of a rapid screen for the endodermal differentiation potential of human pluripotent stem cell lines
Authors: Siller Richard , Naumovska Elena , Mathapati Santosh , Lycke Max , Greenhough Sebastian , Sullivan Gareth J.
Published: November 2016

A challenge facing the human pluripotent stem cell (hPSC) field is the variability observed in differentiation potential of hPSCs. Variability can lead to time consuming and costly optimisation to yield the cell type of interest. This is especially relevant for the differentiation of hPSCs towards the endodermal lineages. Endodermal cells have the potential to yield promising new knowledge and therapies for diseases affecting multiple organ systems, including lung, thymus, intestine, pancreas and liver, as well as applications in regenerative medicine and toxicology. Providing a means to rapidly, cheaply and efficiently assess the differentiation potential of multiple hPSCs is of great interest. To this end, we have developed a rapid small molecule based screen to assess the endodermal potential (EP) of hPSCs, based solely on definitive endoderm (DE) morphology. This drastically reduces the cost and time to identify lines suitable for use in deriving endodermal lineages. We demonstrate the efficacy of this screen using 10 different hPSCs, including 4 human embryonic stem cell lines (hESCs) and 6 human induced pluripotent stem cell lines (hiPSCs). The screen clearly revealed lines amenable to endodermal differentiation, and only lines that passed our morphological assessment were capable of further differentiation to hepatocyte like cells (HLCs).
The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels
Authors: Akpınar Hatice , Nazıroğlu Mustafa , Övey İshak Suat , Çiğ Bilal , Akpınar Orhan
Published: November 2016

Dexmedetomidine (DEX) may act as an antioxidant through regulation of TRPM2 and TRPV1 channel activations in the neurons by reducing cerebral ischemia-induced oxidative stress and apoptosis. The neuroprotective roles of DEX were tested on cerebral ischemia (ISC) in the cultures of rat primary hippocampal and DRG neurons. Fifty-six rats were divided into five groups. A placebo was given to control, sham control, and ISC groups, respectively. In the third group, ISC was induced. The DEX and ISC+DEX groups received intraperitoneal DEX (40 μg/kg) 3, 24, and 48 hours after ISC induction. DEX effectively reversed capsaicin and cumene hydroperoxide/ADP-ribose-induced TRPV1 and TRPM2 densities and cytosolic calcium ion accumulation in the neurons, respectively. In addition, DEX completely reduced ISC-induced oxidative toxicity and apoptosis through intracellular reactive oxygen species production and depolarization of mitochondrial membrane. The DEX and ISC+DEX treatments also decreased the expression levels of caspase 3, caspase 9, and poly (ADP-ribose) polymerase in the hippocampus and DRG. In conclusion, the current results are the first to demonstrate the molecular level effects of DEX on TRPM2 and TRPV1 activation. Therefore, DEX can have remarkable neuroprotective impairment effects in the hippocampus and DRG of ISC-induced rats.
Imaging of surface spin textures on bulk crystals by scanning electron microscopy
Authors: Akamine Hiroshi , Okumura So , Farjami Sahar , Murakami Yasukazu , Nishida Minoru
Published: November 2016

Direct observation of magnetic microstructures is vital for advancing spintronics and other technologies. Here we report a method for imaging surface domain structures on bulk samples by scanning electron microscopy (SEM). Complex magnetic domains, referred to as the maze state in CoPt/FePt alloys, were observed at a spatial resolution of less than 100 nm by using an in-lens annular detector. The method allows for imaging almost all the domain walls in the mazy structure, whereas the visualisation of the domain walls with the classical SEM method was limited. Our method provides a simple way to analyse surface domain structures in the bulk state that can be used in combination with SEM functions such as orientation or composition analysis. Thus, the method extends applications of SEM-based magnetic imaging, and is promising for resolving various problems at the forefront of fields including physics, magnetics, materials science, engineering, and chemistry.
p53 isoform Δ133p53 promotes efficiency of induced pluripotent stem cells and ensures genomic integrity during reprogramming
Authors: Gong Lu , Pan Xiao , Chen Haide , Rao Lingjun , Zeng Yelin , Hang Honghui , Peng Jinrong , Xiao Lei , Chen Jun
Published: November 2016

Human induced pluripotent stem (iPS) cells have great potential in regenerative medicine, but this depends on the integrity of their genomes. iPS cells have been found to contain a large number of de novo genetic alterations due to DNA damage response during reprogramming. Thus, to maintain the genetic stability of iPS cells is an important goal in iPS cell technology. DNA damage response can trigger tumor suppressor p53 activation, which ensures genome integrity of reprogramming cells by inducing apoptosis and senescence. p53 isoform Δ133p53 is a p53 target gene and functions to not only antagonize p53 mediated apoptosis, but also promote DNA double-strand break (DSB) repair. Here we report that Δ133p53 is induced in reprogramming. Knockdown of Δ133p53 results 2-fold decrease in reprogramming efficiency, 4-fold increase in chromosomal aberrations, whereas overexpression of Δ133p53 with 4 Yamanaka factors showes 4-fold increase in reprogamming efficiency and 2-fold decrease in chromosomal aberrations, compared to those in iPS cells induced only with 4 Yamanaka factors. Overexpression of Δ133p53 can inhibit cell apoptosis and promote DNA DSB repair foci formation during reprogramming. Our finding demonstrates that the overexpression of Δ133p53 not only enhances reprogramming efficiency, but also results better genetic quality in iPS cells.
Influence of combined fundamental potentials in a nonlinear vibration energy harvester
Authors: Podder Pranay , Mallick Dhiman , Amann Andreas , Roy Saibal
Published: November 2016

Ambient mechanical vibrations have emerged as a viable energy source for low-power wireless sensor nodes aiming the upcoming era of the ‘Internet of Things’. Recently, purposefully induced dynamical nonlinearities have been exploited to widen the frequency spectrum of vibration energy harvesters. Here we investigate some critical inconsistencies between the theoretical formulation and applications of the bistable Duffing nonlinearity in vibration energy harvesting. A novel nonlinear vibration energy harvesting device with the capability to switch amidst individually tunable bistable-quadratic, monostable-quartic and bistable-quartic potentials has been designed and characterized. Our study highlights the fundamentally different large deflection behaviors of the theoretical bistable-quartic Duffing oscillator and the experimentally adapted bistable-quadratic systems, and underlines their implications in the respective spectral responses. The results suggest enhanced performance in the bistable-quartic potential in comparison to others, primarily due to lower potential barrier and higher restoring forces facilitating large amplitude inter-well motion at relatively lower accelerations.
5-HTR3 and 5-HTR4 located on the mitochondrial membrane and functionally regulated mitochondrial functions
Authors: Wang Qingyi , Zhang Huiyuan , Xu Hao , Guo Dongqing , Shi Hui , Li Yuan , Zhang Weiwei , Gu Yuchun
Published: November 2016

5-HT has been reported to possess significant effects on cardiac activities, but activation of 5-HTR on the cell membrane failed to illustrate the controversial cardiac reaction. Because 5-HT constantly comes across the cell membrane via 5-HT transporter (5-HTT) into the cytoplasm, whether 5-HTR is functional present on the cellular organelles is unknown. Here we show 5-HTR3 and 5-HTR4 were located in cardiac mitochondria, and regulated mitochondrial activities and cellular functions. Knock down 5-HTR3 and 5-HTR4 in neonatal cardiomyocytes resulted in significant increase of cell damage in response to hypoxia, and also led to alternation in heart beating. Activation of 5-HTR4 attenuated mitochondrial Ca2+ uptake under the both normoxic and hypoxic conditions, whereas 5-HTR3 augmented Ca2+ uptake only under hypoxia. 5-HTR3 and 5-HTR4 exerted the opposite effects on the mitochondrial respiration: 5-HTR3 increased RCR (respiration control ratio), but 5-HTR4 reduced RCR. Moreover, activation of 5-HTR3 and 5-HTR4 both significantly inhibited the opening of mPTP. Our results provided the first evidence that 5-HTR as a GPCR and an ion channel, functionally expressed in mitochondria and participated in the mitochondria function and regulation to maintain homeostasis of mitochondrial [Ca2+], ROS, and ATP generation efficiency in cardiomyocytes in response to stress and O2 tension.
Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells
Authors: Qin Jinhua , Chang Mingyang , Wang Shuyong , Liu Zhenbo , Zhu Wei , Wang Yi , Yan Fang , Li Jian , Zhang Bowen , Dou Guifang , Liu Jiang , Pei Xuetao , Wang Yunfang
Published: November 2016

Gap junction-mediated cell-cell interactions are highly conserved and play essential roles in cell survival, proliferation, differentiation and patterning. We report that Connexin 32 (Cx32)-mediated gap junctional intercellular communication (GJIC) is necessary for human embryonic stem cell-derived hepatocytes (hESC-Heps) during step-wise hepatic lineage restriction and maturation. Vitamin K2, previously shown to promote Cx32 expression in mature hepatocytes, up-regulated Cx32 expression and GJIC activation during hepatic differentiation and maturation, resulting in significant increases of hepatic markers expression and hepatocyte functions. In contrast, negative Cx32 regulator 2-aminoethoxydiphenyl borate blocked hESC-to-hepatocyte maturation and muted hepatocyte functions through disruption of GJIC activities. Dynamic gap junction organization and internalization are phosphorylation-dependent and the p38 mitogen-activated protein kinases pathway (MAPK) can negatively regulate Cxs through phosphorylation-dependent degradation of Cxs. We found that p38 MAPK inhibitor SB203580 improved maturation of hESC-Heps correlating with up-regulation of Cx32; by contrast, the p38 MAPK activator, anisomycin, blocked hESC-Heps maturation correlating with down-regulation of Cx32. These results suggested that Cx32 is essential for cell-cell interactions that facilitate driving hESCs through hepatic-lineage maturation. Regulators of both Cx32 and other members of its pathways maybe used as a promising approach on regulating hepatic lineage restriction of pluripotent stem cells and optimizing their functional maturation.
Screening on binary Ti alloy with excellent mechanical property and castability for dental prosthesis application
Authors: Li H. F. , Qiu K. J. , Yuan W. , Zhou F. Y. , Wang B. L. , Li L. , Zheng Y. F. , Liu Y. H.
Published: November 2016

In the present study, the microstructure, mechanical property, castability, corrosion behavior andin vitrocytocompatibility of binary Ti–2X alloys with various alloying elements, including Ag, Bi, Ga, Ge, Hf, In, Mo, Nb, Sn and Zr, were systematically investigated, in order to assess their potential applications in dental field. The experimental results showed that all binary Ti‒2X alloys consisted entirelyα–Ti phase. The tensile strength and microhardness of Ti were improved by adding alloying elements. The castability of Ti was significantly improved by separately adding 2 wt.% Bi, Ga, Hf, Mo, Nb, Sn and Zr. The corrosion resistance of Ti in both normal artificial saliva solution (AS) and extreme artificial saliva solution (ASFL, AS with 0.2 wt.% NaF and 0.3 wt.% lactic acid) has been improved by separately adding alloying elements. In addition, the extracts of studied Ti‒2X alloys produced no significant deleterious effect to both fibroblasts L929 cells and osteoblast-like MG63 cells, indicating a goodin vitrocytocompatibility, at the same level as pure Ti. The combination of enhanced mechanical properties, castability, corrosion behavior, andin vitrocytocompatibility make the developed Ti‒2X alloys have great potential for future stomatological applications.
Electrical Stimulus Controlled Binding/Unbinding of Human Thrombin-Aptamer Complex
Authors: Gosai Agnivo , Ma Xiao , Balasubramanian Ganesh , Shrotriya Pranav
Published: November 2016

The binding/unbinding of the human thrombin and its 15-mer single stranded DNA aptamer, under the application of external stimulus in the form of electrostatic potential/electric field, is investigated by a combination of continuum analysis and atomistic molecular dynamics simulation. In agreement with the experiments that demonstrate the influence of electrostatic potential on the thrombin/aptamer complex, our computations show that the application of positive electric field successfully unbinds the thrombin from the aptamer. Results from umbrella sampling simulations reveal that there is a decrease in the free energy of binding between the thrombin and aptamer in presence of positive electric fields. Hydrogen bonding and non-bonded interaction energies, and hence the free energy of binding, between the thrombin and its aptamer reduce as the applied electric field is shifted from negative to positive values. Our analyses demonstrate that application of electrical stimulus modifies the molecular interactions within the complex and consequently, electrical field can be used to modulate the association between the thrombin and its aptamer.
Natural zwitterionic betaine enables cells to survive ultrarapid cryopreservation
Authors: Yang Jing , Cai Nana , Zhai Hongwen , Zhang Jiamin , Zhu Yingnan , Zhang Lei
Published: November 2016

Cryoprotectants (CPAs) play a critical role in cryopreservation because they can resist the cell damage caused by the freezing process. Current state-of-the-art CPAs are mainly based on an organic solvent dimethyl sulfoxide (DMSO), and several DMSO-cryopreserved cell products have been brought to market. However, the intrinsic toxicity and complex freezing protocol of DMSO still remain as the bottleneck of the wide use for clinical applications. Herein, we reported that betaine, a natural zwitterionic molecule, could serve as a nontoxic and high efficient CPA. At optimum concentration of betaine, different cell types exhibited exceptional post-thaw survival efficiency with ultrarapid freezing protocol, which was straightforward, cost efficient but difficult to succeed using DMSO. Moreover, betaine showed negligible cytotoxicity even after long-term exposure of cells. Mechanistically, we hypothesized that betaine could be ultra-rapidly taken up by cells for intracellular protection during the freezing process. This technology unlocks the possibility of alternating the traditional toxic CPAs and is applicable to a variety of clinical applications.
Genomic regions responsible for amenability to Agrobacterium-mediated transformation in barley
Authors: Hisano Hiroshi , Sato Kazuhiro
Published: November 2016

Different plant cultivars of the same genus and species can exhibit vastly different genetic transformation efficiencies. However, the genetic factors underlying these differences in transformation rate remain largely unknown. In barley, ‘Golden Promise’ is one of a few cultivars reliable for Agrobacterium-mediated transformation. By contrast, cultivar ‘Haruna Nijo’ is recalcitrant to genetic transformation. We identified genomic regions of barley important for successful transformation with Agrobacterium, utilizing the ‘Haruna Nijo’ × ‘Golden Promise’ F2 generation and genotyping by 124 genome-wide SNP markers. We observed significant segregation distortions of these markers from the expected 1:2:1 ratio toward the ‘Golden Promise’-type in regions of chromosomes 2H and 3H, indicating that the alleles of ‘Golden Promise’ in these regions might contribute to transformation efficiency. The same regions, which we termed Transformation Amenability (TFA) regions, were also conserved in transgenic F2 plants generated from a ‘Morex’ × ‘Golden Promise’ cross. The genomic regions identified herein likely include necessary factors for Agrobacterium-mediated transformation in barley. The potential to introduce these loci into any haplotype of barley opens the door to increasing the efficiency of transformation for target alleles into any haplotype of barley by the TFA-based methods proposed in this report.