bluuebunny/crossref_metadata_2025 huggingface dataset:
Three Years' Experience of Flying
Authors: Hucks B. C. , Bell C. Gordon
Published: February 2017

The primary object of the paper which I had the honour to be asked to read' to you this evening, is not to be a mere recital of my experiences during the three years I have been actively piloting an aeroplane, although it has the title “Three Years’ Flying Experience” but I hope to be able to give to you a few points which should be of general interest, and perhaps beneficial to fellow–pilots and to others who have so kindly come here to–night to hear this paper.

I will first give you a few instances of my earliest failures, their causes and remedies. In fact, the solution of most of my troubles, when I look back, may be placed under the simple headings of inexperience and want of confidence, which, I suppose, are very nearly one and the same thing. The machines of three years ago, jt is true, were not so efficient, nor so safe, but that fact has really, in my opinion, no more than quite a small bearing on the results of those days.
Rigid Airships
Authors: Bartlett J. L.
Published: February 2017

In this lecture it is proposed to deal with the general aerostatical principles governing the flight of lighter-than-air craft, and also to describe briefly the various types of airships, with special reference to the rigid airship.

The future of lighter-than-air craft is undoubtedly dependent upon the development of the rigid airship, in which type of ship efficiency and performance increase at a greater rate than the gross lifting capacity.

To understand the working of a large airship it is essential to have a thorough grasp of the elementary aerostatic principles governing the flight of an ordinary free balloon, so it is proposed, first, to outline these principles and then to pass on to the non-rigid, semi-rigid and rigid types of airships, all of which are virtually balloons of varying type, rendered dirigible by the fitting of means of propulsion, and navigable by the introduction of controlling surfaces.
The Effect of Atmospheric Pressure and Temperature upon the Performance of a Petrol Engine
Authors: Ritchie E. G.
Published: February 2017

The efficiency of all internal combustion engines is influenced to a large degree by the density of the charge prior to ignition. In the stationary engine operating at normal ground density, the variation in compression pressure throughout the range of working conditions is so small as to have no appreciable effect upon engine performance. In the aero engine, however, the conditions obtaining in flight are such as to produce wide variation in the suction pressure and therefore in the compression pressure due to changes in atmospheric density.

Table I has been prepared to show the variation in air pressure, temperature and density with height, the figures given representing the mean conditions obtaining in the south of England.
Incidence Wires
Authors: Hudson Hilda P.
Published: February 2017

The inclusion of incidence wires in strength calculations, by the method of strain energy, makes very little difference in normal flight conditions, but shows, large changes in wing loads in nose diving and in centre section loads with a broken flying wire. There is a serious increase of load in the bottom plane in nose diving.
The Design of Spars With Offset Pin Joints.
Authors: Booth Harris
Published: February 2017

The method here described has some advantages over the present standard method of designing with continuous spars. Firstly, it gives lighter spars by working as many points as possible up to the elastic limit. Secondly, it is far quicker to use owing to the necessary formulæ and processes of computation being more manageable and to the fact that practically each bay can be designed separately without affecting the others. Thirdly, the roughing out and the final checking are done with the same set of formulæ, whereas, if the usual type of spar construction is adopted, it is necessary to use different methods for the preliminary and final design. Fourthly, the accuracy of the work is not affected by the supports getting out of line when the whole structure deflects under load, a serious error in the older method being thus avoided.
Wilbur Wright
Authors: Brewer Griffith
Published: February 2017

The present generation will never completely realise the magnitude of the loss to Aviation caused by the death of Wilbur Wright, and yet it requires but a moment's thought to recognise that his name will live until all histories are obliterated, for with his brother Orville, he accomplished the dream of ages, which men of acknowledged science had become in the habit of first attempting to accomplish, and then alleging the feat to be amongst the unattainable.

There are only three ways of getting from one place to another on this earth; one is on land, the next is on water, and the third is now through the air. Certainly it was possible to travel in the air to destinations settled by the caprice of the wind, but to do the same as the birds, and travel from one place to another, had never been possible until Wilbur and Orville Wright accomplished mechanical flight in 1903.
The Vertical Screw Aërial Machine, with Special Notes on the Lifting Propellers
Authors: William George Walker C.E.
Published: February 2017

This machine was taken in hand in 1899 with the assistance of Mr. P. Y. Alexander. A staff of competent draughtsmen were employed in getting out fully detailed working drawings of different powers. The propellers are 30 feet in diameter revolving in opposite directions mounted on, separate shafts, one inside the other, by this means the necessary reactions for rotation is obtained. The steam engines are below; the engines in this particular design are of somewhat novel type; the bed plate cylinders are connected to one of the shafts, the outer one, and the crank shafts to the inner one, so that we have the engine bed cylinders, etc., revolving in one direction, and the crank shaft in the opposite direction.
Angle of Incidence
Authors: Wright Wilbur
Published: February 2017

If the term “ angle of incidence,” so frequently used in aeronautical discussions, could be confined to a single definite meaning, viz., the angle at which aeroplane and wind actually meet, much error and confusion Would be averted. But many of the best writers use this term loosely and inexactly, with the result that their calculations and explanations of phenomena are thereby often rendered of little value, and students are misled.

If a plane be held stationary in a horizontal wind (Fig. 1), the angle of incidence A C D will be equal to the angle with the horizon. But if the wind have an upward trend, the angle of incidence will be increased to A C D2. A calculation based on the assumption that A C D still remained the true angle would, of course, be seriously in error.

If it be assumed (Fig. 2) that the wind moves from D2 to C, while the plane moves from E to C, the angle of incidence will become A C D3.
The Zeppelin Airship
Authors: Maxim Hiram Stevens
Published: February 2017

I have been asked to give my opinion in regard to the value of the experiments of Count Zeppelin. I have made a close study of balloons for many years, and have followed very closely the experiments of Gaston Tissandier and Commandant Renard. In the experiments of Gaston Tissandier, the balloon was made cigar-shape, both ends being practically alike. The propelling force was a screw driven by an electrical engine. The machine was very carefully made, and was probably as beautiful a piece of workmanship as ever has been turned out. It was inflated with pure hydrogen. When it was tried, it rose in the air to perfection, and moved at a low velocity by means of its own screw and motive power, but the velocity through’ the air was considerably less than the velocity of the air itself, consequently it moved along with the wind very much like any other balloon. Other experiments were made, and it was found that the cigar–shape was not so favourable as a fishshape balloon.
The Computation of Aerodynamic Support
Authors: Shaw W. R. D.
Published: February 2017

The function of an aerofoil of circular arc camber is to impart motion in a circular path to a mass of air whose volume is determined by the product of span, chord, and mean sweep, the latter being a linear measure of the depth of the strata of air affected above and below the surface.
“Flying in Clouds”
Authors: Fowler Henry
Published: February 2017

From Captain Hucks’ remarks on the difficulties of keeping a straight course when flying in clouds, and the impossibility of relying upon the compass as a guide when out of sight of a fixed point of reference, it would appear that the nature of the errors to which a compass is liable, and the circumstances under which it may be relied upon are not generally known.

Much work has been done at the Royal Aircraft Factory in the last three years on the behaviour of compasses in the air, and the directions to be followed in their design in order to avoid their errors as far as possible. This work was chiefly done by the late Captain Keith Lucas, F.R.S., who was unfortunately killed when learning to fly, in the autumn of last year. The following is a short statement as to what may be expected from compasses in aeroplanes:—

On account of the dip the N. point of the compass card, when an aeroplane is turning, always tends to point too much towards the centre of the turn, the amount of error varying according to the bearing from which the turn is made.
Loss of BRG1 induces CRC cell senescence by regulating p53/p21 pathway
Authors: Wang Guihua , Fu Yinjia , Hu Fuqing , Lan Jinqing , Xu Feng , Yang Xi , Luo Xuelai , Wang Jing , Hu Junbo
Published: February 2017

Brahma-related gene-1 (BRG1) is the specific ATPase of switch/sucrose nonfermentable chromatin-remodeling complex that is aberrantly expressed or mutated in various cancers. However, the exact role of BRG1 in oncogenesis remains unknown. In this study, we demonstrate that the knockdown (KD) of BRG1 promotes cellular senescence by influencing the SIRT1/p53/p21 signal axis in colorectal cancer (CRC). In particular, we reveal that the expression level of BRG1 is inversely correlated with p21, one of the classic senescence regulators, and is decreased in senescent CRC cells. KD of BRG1 promoting senescence is indicated by the increase of senescence-associated β-galactosidase (SA-β-gal) activity, inhibition of cell proliferation, induction of cell cycle arrest, and formation of senescence-associated heterochromatin foci. BRG1 binds to SIRT1 and interferes with SIRT1-mediated deacetylation of p53 at K382. Rescue experiments by co-silencing p53 or treatment with EX527, a SIRT1-specific inhibitor, abrogated the cellular senescence induced by KD of BRG1. BRG1 KD cells resulted in smaller tumor formation than that in control cells in vivo. Collectively, our study shows that BRG1 has an important role in cellular senescence and tumor growth. The BRG1/SIRT1/p53 signal axis is a novel mechanism of cell senescence in CRC and is a new potential target for cancer therapy.
Tenovin-6 impairs autophagy by inhibiting autophagic flux
Authors: Yuan Hongfeng , Tan Brandon , Gao Shou-Jiang
Published: February 2017

Tenovin-6 has attracted significant interest because it activates p53 and inhibits sirtuins. It has anti-neoplastic effects on multiple hematopoietic malignancies and solid tumors in both in vitro and in vivo studies. Tenovin-6 was recently shown to impair the autophagy pathway in chronic lymphocytic leukemia cells and pediatric soft tissue sarcoma cells. However, whether tenovin-6 has a general inhibitory effect on autophagy and whether there is any involvement with SIRT1 and p53, both of which are regulators of the autophagy pathway, remain unclear. In this study, we have demonstrated that tenovin-6 increases microtubule-associated protein 1 light chain 3 (LC3-II) level in diverse cell types in a time- and dose-dependent manner. Mechanistically, the increase of LC3-II by tenovin-6 is caused by inhibition of the classical autophagy pathway via impairing lysosomal function without affecting the fusion between autophagosomes and lysosomes. Furthermore, we have revealed that tenovin-6 activation of p53 is cell type dependent, and tenovin-6 inhibition of autophagy is not dependent on its regulatory functions on p53 and SIRT1. Our results have shown that tenovin-6 is a potent autophagy inhibitor, and raised the precaution in interpreting results where tenovin-6 is used as an inhibitor of SIRT1.
Duodenal GLP-1 signaling regulates hepatic glucose production through a PKC-δ-dependent neurocircuitry
Authors: Yang Mengliu , Wang Jinzhi , Wu Shaobo , Yuan Lei , Zhao Xiaodong , Liu Chaohong , Xie Jing , Jia Yanjun , Lai Yerui , Zhao Allan Zijian , Boden Guenther , Li Ling , Yang Gangyi
Published: February 2017

Intestinal glucagon-like peptide-1 (GLP-1) is a hormone that stimulates insulin secretion and acts as a neuropeptide to control glucose homeostasis, but little is known whether intestinal GLP-1 has any effect in the control of hepatic glucose production (HGP). Here we found that intraduodenal infusion of GLP-1 activated duodenal PKC-δ, lowered HGP and was accompanied by a decrease in hepatic expression of gluconeogenic enzymes and an increase in hepatic insulin signaling in rats. However, gut co-infusion of either the GLP-1 receptor antagonist Ex-9, or the PKC-δ inhibitor rottlerin with GLP-1, negated the ability of gut GLP-1 to lower HGP and to increase hepatic insulin signaling during clamps. The metabolic and molecular signal effects of duodenal GLP-1 were also negated by co-infusion with tetracaine, pharmacologic inhibition of N-methyl-d-aspartate receptors within the dorsalvagal complex, or hepatic vagotomy in rats. In summary, we identified a neural glucoregulatory function of gut GLP-1 signaling.
Knockdown of long non-coding RNA HOTAIR increases miR-454-3p by targeting Stat3 and Atg12 to inhibit chondrosarcoma growth
Authors: Bao Xing , Ren Tingting , Huang Yi , Sun Kunkun , Wang Shidong , Liu Kuisheng , Zheng Bingxin , Guo Wei
Published: February 2017

Current practices for the therapy of chondrosarcoma, including wide-margin surgical resection and chemotherapy, are less than satisfactory. Recently, emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) have an essential role in the initiation and progression of tumors. As a typical lncRNA, HOTAIR is significantly overexpressed in various tumors. However, the function and potential biological mechanisms of HOTAIR in human chondrosarcoma remain unknown. Quantitative RT-PCR demonstrated that HOTAIR expression was upregulated in chondrosarcoma tissues and cell lines. High HOTAIR expression is correlated with tumor stage and poor prognosis. Functional experiments reveal that HOTAIR knockdown leads to growth inhibition of human chondrosarcoma cells in vitro and in vivo. In addition to cycle arrest and apoptosis, knockdown of HOTAIR inhibits autophagy, which favors cell death. Mechanistically, we demonstrated that HOTAIR induced DNA methylation of miR-454-3p by recruiting EZH2 and DNMT1 to the miR-454-3p promoter regions, which markedly silences miR-454-3p expression. Further analysis revealed that STAT3 and ATG12 are targets of miR-454-3p, initiate HOTAIR deficiency-induced apoptosis and reduce autophagy. Collectively, our data reveal the roles and functional mechanisms of HOTAIR in human chondrosarcoma and suggest that HOTAIR may act as a prognostic biomarker and potential therapeutic target for chondrosarcoma.
RASAL2, a RAS GTPase-activating protein, inhibits stemness and epithelial–mesenchymal transition via MAPK/SOX2 pathway in bladder cancer
Authors: Hui Ke , Gao Yang , Huang Jun , Xu Shan , Wang Bin , Zeng Jin , Fan Jinhai , Wang Xinyang , Yue Yangyang , Wu Shiqi , Hsieh Jer-Tsong , He Dalin , Wu Kaijie
Published: February 2017

Muscle-invasive or metastatic bladder cancer (BCa) is associated with a very poor prognosis, and the underlying mechanism remains poorly understood. In this study, we demonstrate RASAL2, a RAS GTPase-activating protein (RAS GAP), acts as a tumor suppressor in BCa. First, RASAL2 was downregulated in BCa specimens and inversely correlated with pathological grades and clinical stages. Furthermore, we observed that RASAL2 could inhibit BCa stemness and epithelial–mesenchymal transition (EMT) based on our gain-of-function and loss-of-function experiments. Mechanistically, we found that mitogen-activated protein kinase/SOX2 signaling had a critical role for maintaining the stemness and mesenchymal properties of RASAL2-deficient BCa cells because inhibition of ERK activity or knockdown of SOX2 could reverse these phenotypes. Also, RASAL2 could inhibit BCa tumorigenesis and distant metastasis in vivo. Moreover, there was an inverse correlation between RASAL2 expression and the stemness/EMT status in subcutaneous xenograft and human BCa specimens. Taken together, our data indicate that RASAL2 is a tumor suppressor in BCa, and modulates cancer stemness and EMT for BCa recurrence and metastasis.
Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling
Authors: Liu Chun-Hua , Gong Zheng , Liang Zong-Lai , Liu Zhi-Xin , Yang Fan , Sun Yu-Jing , Ma Ming-Liang , Wang Yi-Jing , Ji Chao-Ran , Wang Yu-Hong , Wang Mei-Jie , Cui Fu-Ai , Lin Amy , Zheng Wen-Shuai , He Dong-Fang , Qu Chang-xiu , Xiao Peng , Liu Chuan-Yong , Thomsen Alex R. B. , Joseph Cahill Thomas , Kahsai Alem W. , Yi Fan , Xiao Kun-Hong , Xue Tian , Zhou Zhuan , Yu Xiao , Sun Jin-Peng
Published: February 2017

Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by β-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-β-arrestin-1 signalling complex. Replacing the C-terminal region of β-arrestin-1 with its counterpart on β-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between β-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes.
Magnetism and local symmetry breaking in a Mott insulator with strong spin orbit interactions
Authors: Lu L. , Song M. , Liu W. , Reyes A. P. , Kuhns P. , Lee H. O. , Fisher I. R. , Mitrović V. F.
Published: February 2017

Study of the combined effects of strong electronic correlations with spin-orbit coupling (SOC) represents a central issue in quantum materials research. Predicting emergent properties represents a huge theoretical problem since the presence of SOC implies that the spin is not a good quantum number. Existing theories propose the emergence of a multitude of exotic quantum phases, distinguishable by either local point symmetry breaking or local spin expectation values, even in materials with simple cubic crystal structure such as Ba2NaOsO6. Experimental tests of these theories by local probes are highly sought for. Our local measurements designed to concurrently probe spin and orbital/lattice degrees of freedom of Ba2NaOsO6 provide such tests. Here we show that a canted ferromagnetic phase which is preceded by local point symmetry breaking is stabilized at low temperatures, as predicted by quantum theories involving multipolar spin interactions.
Ultrafast radiative heat transfer
Authors: Yu Renwen , Manjavacas Alejandro , García de Abajo F. Javier
Published: February 2017

Light absorption in conducting materials produces heating of their conduction electrons, followed by relaxation into phonons within picoseconds, and subsequent diffusion into the surrounding media over longer timescales. This conventional picture of optical heating is supplemented by radiative cooling, which typically takes place at an even lower pace, only becoming relevant for structures held in vacuum or under extreme thermal isolation. Here, we reveal an ultrafast radiative cooling regime between neighboring plasmon-supporting graphene nanostructures in which noncontact heat transfer becomes a dominant channel. We predict that more than 50% of the electronic heat energy deposited on a graphene disk can be transferred to a neighboring nanoisland within a femtosecond timescale. This phenomenon is facilitated by the combination of low electronic heat capacity and large plasmonic field concentration in doped graphene. Similar effects should occur in other van der Waals materials, thus opening an unexplored avenue toward efficient heat management.
GIGANTEA is a co-chaperone which facilitates maturation of ZEITLUPE in the Arabidopsis circadian clock
Authors: Cha Joon-Yung , Kim Jeongsik , Kim Tae-Sung , Zeng Qingning , Wang Lei , Lee Sang Yeol , Kim Woe-Yeon , Somers David E.
Published: February 2017

Circadian clock systems help establish the correct daily phasing of the behavioral, developmental, and molecular events needed for the proper coordination of physiology and metabolism. The circadian oscillator comprises transcription–translation feedback loops but also requires post-translational processes that regulate clock protein homeostasis. GIGANTEA is a unique plant protein involved in the maintenance and control of numerous facets of plant physiology and development. Through an unknown mechanism GIGANTEA stabilizes the F-box protein ZEITLUPE, a key regulator of the circadian clock. Here, we show that GIGANTEA has general protein chaperone activity and can act to specifically facilitate ZEITLUPE maturation into an active form in vitro and in planta. GIGANTEA forms a ternary complex with HSP90 and ZEITLUPE and its co-chaperone action synergistically enhances HSP90/HSP70 maturation of ZEITLUPE in vitro. These results identify a molecular mechanism for GIGANTEA activity that can explain its wide-ranging role in plant biology.
Women prefer men who use metaphorical language when paying compliments in a romantic context
Authors: Gao Zhao , Gao Shan , Xu Lei , Zheng Xiaoxiao , Ma Xiaole , Luo Lizhu , Kendrick Keith M.
Published: February 2017

Language plays an important role in romantic attachment. However, it is unclear whether the structure and topic of language use might influence potential mate choice. We investigated 124 female students’ preference for compliments paid by males incorporating either literal or metaphoric (conventional/novel) language and targeting their appearance or possessions (house) throughout their menstrual cycle. Male faces paired with novel metaphorical compliments were rated as more attractive by women than those paired with literal ones. Compliments targeting appearance increased male attractiveness more than possessions. Interestingly, compliments on appearance using novel metaphors were preferred by women in a relationship during the fertile phase but by single women during the luteal phase. A similar pattern of altered face attraction ratings was subsequently shown by subjects in the absence of the verbal compliments and even though they were unable to recognize the faces. Thus the maintained attraction bias for faces previously associated with figurative language compliments appears to be unconscious. Overall this study provides the first evidence that women find men who typically use novel metaphorical language to compliment appearance more attractive than those using prosaic language or complimenting possessions. The evolutionary significance for such a language use bias in mate selection is discussed.
Correction: Corrigendum: Kinetic Measurements Reveal Enhanced Protein-Protein Interactions at Intercellular Junctions
Authors: Shashikanth Nitesh , Kisting Meridith A. , Leckband Deborah E.
Published: February 2017

Scientific Reports 6: Article number: 23623; published online: 24 March 2016; updated: 09 February 2017 This Article contains an error in the Acknowledgments section where: “This work was supported, in part, by National Institutes of Health Grant 5 RO1 GM097443 (to D.E.L.) and by National Science Foundation (NSF) Grant CMMI 10-29871 (to D.
Multivariate approach to quantitative analysis of Aphis gossypii Glover (Hemiptera: Aphididae) and their natural enemy populations at different cotton spacings
Authors: Malaquias José B. , Ramalho Francisco S. , dos S. Dias Carlos T. , Brugger Bruno P. , S. Lira Aline Cristina , Wilcken Carlos F. , Pachú Jéssica K. S. , Zanuncio José C.
Published: February 2017

The relationship between pests and natural enemies using multivariate analysis on cotton in different spacing has not been documented yet. Using multivariate approaches is possible to optimize strategies to controlAphis gossypiiat different crop spacings because the possibility of a better use of the aphid sampling strategies as well as the conservation and release of its natural enemies. The aims of the study were (i) to characterize the temporal abundance data of aphids and its natural enemies using principal components, (ii) to analyze the degree of correlation between the insects and between groups of variables (pests and natural enemies), (iii) to identify the main natural enemies responsible for regulatingA. gossypiipopulations, and (iv) to investigate the similarities in arthropod occurrence patterns at different spacings of cotton crops over two seasons. High correlations in the occurrence ofScymnus rubicunduswith aphids are shown through principal component analysis and through the important role the species plays in canonical correlation analysis. Clustering the presence of apterous aphids matches the pattern verified forChrysoperla externaat the three different spacings between rows. Our results indicate thatS. rubicundusis the main candidate to regulate the aphid populations in all spacings studied.
Correction: Corrigendum: ROS-mediated iron overload injures the hematopoiesis of bone marrow by damaging hematopoietic stem/progenitor cells in mice
Authors: Chai Xiao , Li Deguan , Cao Xiaoli , Zhang Yuchen , Mu Juan , Lu Wenyi , Xiao Xia , Li Chengcheng , Meng Juanxia , Chen Jie , Li Qing , Wang Jishi , Meng Aimin , Zhao Mingfeng
Published: February 2017

Scientific Reports 5: Article number: 10181; published online: 13 May 2015; updated: 09 February 2017 The iron-overload mouse model used in this study was previously reported by the authors in references 1 and 2, which are not cited in the Article. The data supporting the mouse model is presented inFigure 1 of the Article.
Visual cortex and cerebellum hyperactivation during negative emotion picture stimuli in migraine patients
Authors: Wang Mengxing , Su Jingjing , Zhang Jilei , Zhao Ying , Yao Qian , Zhang Qiting , Zhang Hui , Wang Shuo , Li Ge-Fei , Liu Jian-Ren , Du Xiaoxia
Published: February 2017

Migraines are a common and undertreated disease and often have psychiatric comorbidities; however, the abnormal mechanism of emotional processing in migraine patients has not been well clarified. This study sought to investigate the different brain functional activation to neutral, positive and negative emotional stimuli between migraine and healthy subjects. Twenty-six adults with migraines and 26 healthy adults, group-matched for sex and age, participated in this experiment. Although there were no significant differences between two groups during the viewing of positive affective pictures vs. neutral affective pictures, there were different activation patterns during the viewing of negative to neutral affective pictures in the two groups; the control group showed both increased and decreased activation patterns, while the migraine subjects showed only increased activation. Negative affective pictures elicited stronger activation than neutral affective pictures in migraineurs, which included the bilateral cerebellum anterior lobe/culmen, the bilateral lingual gyri, the bilateral precuneus and the left cuneus. Our data indicated that migraine patients were hypersensitive to negative stimuli, which might provide clues to aid in the understanding of the pathophysiology and psychiatric comorbidities of migraines.
Fe doped Magnetic Nanodiamonds made by Ion Implantation
Authors: Chen ChienHsu , Cho I. C. , Jian Hui-Shan , Niu H.
Published: February 2017

Here we present a simple physical method to prepare magnetic nanodiamonds (NDs) using high dose Fe ion-implantation. The Fe atoms are embedded into NDs through Fe ion-implantation and the crystal structure of NDs are recovered by thermal annealing. The results of TEM and Raman examinations indicated the crystal structure of the Fe implanted NDs is recovered completely. The SQUID-VSM measurement shows the Fe-NDs possess room temperature ferromagnetism. That means the Fe atoms are distributed inside the NDs without affecting NDs crystal structure, so the NDs can preserve the original physical and chemical properties of the NDs. In addition, the ion-implantation-introduced magnetic property might make the NDs to become suitable for variety of medical applications.
Analysis of Influenza and RSV dynamics in the community using a ‘Local Transmission Zone’ approach
Authors: Almogy Gal , Stone Lewi , Bernevig B. Andrei , Wolf Dana G. , Dorozko Marina , Moses Allon E. , Nir-Paz Ran
Published: February 2017

Understanding the dynamics of pathogen spread within urban areas is critical for the effective prevention and containment of communicable diseases. At these relatively small geographic scales, short-distance interactions and tightly knit sub-networks dominate the dynamics of pathogen transmission; yet, the effective boundaries of these micro-scale groups are generally not known and often ignored. Using clinical test results from hospital admitted patients we analyze the spatio-temporal distribution of Influenza Like Illness (ILI) in the city of Jerusalem over a period of three winter seasons. We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy.
Epigenetic Editing of Ascl1 Gene in Neural Stem Cells by Optogenetics
Authors: Lo Chiao-Ling , Choudhury Samrat Roy , Irudayaraj Joseph , Zhou Feng C.
Published: February 2017

Enzymes involved in epigenetic processes such as methyltransferases or demethylases are becoming highly utilized for their persistent DNA or histone modifying efficacy. Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1), a candidate proneuron gene. Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing. A differentially methylated region at the Ascl1 promoter, isolated from murine dorsal root ganglion (hypermethylated) and striated cells (hypomethylated), was targeted with these optogenetic-epigenetic constructs. Optimized blue-light illumination triggered the co-localization of TALE constructs with DNMT3A-CD or TET1-CD fusion proteins at the targeted site of the Ascl1 promoter. We found that this spatiotemporal association of the fusion proteins selectively alters the methylation state and also regulates gene activity. This proof of concept developed herein holds immense promise for the ability to regulate gene activity via epigenetic modulation with spatiotemporal precision.
Whole exome sequencing using Ion Proton system enables reliable genetic diagnosis of inherited retinal dystrophies
Authors: Riera Marina , Navarro Rafael , Ruiz-Nogales Sheila , Méndez Pilar , Burés-Jelstrup Anniken , Corcóstegui Borja , Pomares Esther
Published: February 2017

Inherited retinal dystrophies (IRD) comprise a wide group of clinically and genetically complex diseases that progressively affect the retina. Over recent years, the development of next-generation sequencing (NGS) methods has transformed our ability to diagnose heterogeneous diseases. In this work, we have evaluated the implementation of whole exome sequencing (WES) for the molecular diagnosis of IRD. Using Ion ProtonTM system, we simultaneously analyzed 212 genes that are responsible for more than 25 syndromic and non-syndromic IRD. This approach was used to evaluate 59 unrelated families, with the pathogenic variant(s) successfully identified in 71.18% of cases. Interestingly, the mutation detection rate varied substantially depending on the IRD subtype. Overall, we found 63 different mutations (21 novel) in 29 distinct genes, and performed in vivo functional studies to determine the deleterious impact of variants identified in MERTK, CDH23, and RPGRIP1. In addition, we provide evidences that support CDHR1 as a gene responsible for autosomal recessive retinitis pigmentosa with early macular affectation, and present data regarding the disease mechanism of this gene. Altogether, these results demonstrate that targeted WES of all IRD genes is a reliable, hypothesis-free approach, and a cost- and time-effective strategy for the routine genetic diagnosis of retinal dystrophies.
Gfi1Cre mice have early onset progressive hearing loss and induce recombination in numerous inner ear non-hair cells
Authors: Matern Maggie , Vijayakumar Sarath , Margulies Zachary , Milon Beatrice , Song Yang , Elkon Ran , Zhang Xiaoyu , Jones Sherri M. , Hertzano Ronna
Published: February 2017

Studies of developmental and functional biology largely rely on conditional expression of genes in a cell type-specific manner. Therefore, the importance of specificity and lack of inherent phenotypes for Cre-driver animals cannot be overemphasized. The Gfi1Cre mouse is commonly used for conditional hair cell-specific gene deletion/reporter gene activation in the inner ear. Here, using immunofluorescence and flow cytometry, we show that the Gfi1Cre mice produce a pattern of recombination that is not strictly limited to hair cells within the inner ear. We observe a broad expression of Cre recombinase in the Gfi1Cre mouse neonatal inner ear, primarily in inner ear resident macrophages, which outnumber the hair cells. We further show that heterozygous Gfi1Cre mice exhibit an early onset progressive hearing loss as compared with their wild-type littermates. Importantly, vestibular function remains intact in heterozygotes up to 10 months, the latest time point tested. Finally, we detect minor, but statistically significant, changes in expression of hair cell-enriched transcripts in the Gfi1Cre heterozygous mice cochleae compared with their wild-type littermate controls. Given the broad use of the Gfi1Cre mice, both for gene deletion and reporter gene activation, these data are significant and necessary for proper planning and interpretation of experiments.
Transcriptome profiling of Galaxea fascicularis and its endosymbiont Symbiodinium reveals chronic eutrophication tolerance pathways and metabolic mutualism between partners
Authors: Lin Zhenyue , Chen Mingliang , Dong Xu , Zheng Xinqing , Huang Haining , Xu Xun , Chen Jianming
Published: February 2017

In the South China Sea, coastal eutrophication in the Beibu Gulf has seriously threatened reef habitats by subjecting corals to chronic physiological stress. To determine how coral holobionts may tolerate such conditions, we examined the transcriptomes of healthy colonies of the galaxy coral Galaxea fascicularis and its endosymbiont Symbiodinium from two reef sites experiencing pristine or eutrophied nutrient regimes. We identified 236 and 205 genes that were differentially expressed in eutrophied hosts and symbionts, respectively. Both gene sets included pathways related to stress responses and metabolic interactions. An analysis of genes originating from each partner revealed striking metabolic integration with respect to vitamins, cofactors, amino acids, fatty acids, and secondary metabolite biosynthesis. The expression levels of these genes supported the existence of a continuum of mutualism in this coral-algal symbiosis. Additionally, large sets of transcription factors, cell signal transduction molecules, biomineralization components, and galaxin-related proteins were expanded in G. fascicularis relative to other coral species.
Emission properties of Ga2O3 nano-flakes: effect of excitation density
Authors: Pozina G. , Forsberg M. , Kaliteevski M. A. , Hemmingsson C.
Published: February 2017

In the quest of developing high performance electronic and optical devices and more cost effective fabrication processes of monoclinic β-Ga2O3, new growth techniques and fundamental electronic and optical properties of defects have to be explored. By heating of dissolved metallic Ga in HCl in a NH3 and N2 atmosphere, nano-flake films of monoclinic β-phase Ga2O3 were grown as confirmed by XRD. From optical measurements, we observe two strong emissions. A red band peaking at ~2.0 eV and a UV band at ~3.8 eV. The band at ~2.0 eV is attributed to donor-acceptor pair recombination where the donor and acceptor level is suggested to be related to VO and nitrogen, respectively. By studying the dependence of the intensity of the UV band at 3.8 eV versus excitation density, a model is suggested. In the model, it is assumed that local potential fluctuations forming minima (maxima), where the carriers would be localized with a summarized band offset for conduction and valence band of 1 eV. The origin of the fluctuations is tentatively suggested to be related to micro-inclusions of different phases in the film.
The Growth Mechanism of Transition Metal Dichalcogenides by using Sulfurization of Pre-deposited Transition Metals and the 2D Crystal Hetero-structure Establishment
Authors: Wu Chong-Rong , Chang Xiang-Rui , Wu Chao-Hsin , Lin Shih-Yen
Published: February 2017

A growth model is proposed for the large-area and uniform MoS2 film grown by using sulfurization of pre-deposited Mo films on sapphire substrates. During the sulfurization procedure, the competition between the two mechanisms of the Mo oxide segregation to form small clusters and the sulfurization reaction to form planar MoS2 film is determined by the amount of background sulfur. Small Mo oxide clusters are observed under the sulfur deficient condition, while large-area and complete MoS2 films are obtained under the sulfur sufficient condition. Precise layer number controllability is also achieved by controlling the pre-deposited Mo film thicknesses. The drain currents in positive dependence on the layer numbers of the MoS2 transistors with 1-, 3- and 5- layer MoS2 have demonstrated small variation in material characteristics between each MoS2 layer prepared by using this growth technique. By sequential transition metal deposition and sulfurization procedures, a WS2/MoS2/WS2 double hetero-structure is demonstrated. Large-area growth, layer number controllability and the possibility of hetero-structure establishment by using sequential metal deposition and following sulfurization procedures have revealed the potential of this growth technique for practical applications.
Ebola virus infection induces autoimmunity against dsDNA and HSP60
Authors: Fausther-Bovendo H. , Qiu X. , McCorrister S. , Westmacott G. , Sandstrom P. , Castilletti C. , Di Caro A. , Ippolito G. , Kobinger G. P.
Published: February 2017

Ebola virus (EBOV) survivors are affected by a variety of serious illnesses of unknown origin for years after viral clearance from the circulation. Identifying the causes of these persistent illnesses is paramount to develop appropriate therapeutic protocols. In this study, using mouse and non-human primates which survived EBOV challenge, ELISA, western blot, mass spectrometry and flow cytometry were used to screen for autoantibodies, identify their main targets, investigate the mechanism behind their induction and monitor autoantibodies accumulation in various tissues. In infected mice and NHP, polyclonal B cell activation and autoantigens secretion induced autoantibodies against dsDNA and heat shock protein 60 as well as antibody accumulation in tissues associated with long-term clinical manifestations in humans. Finally, the presence of these autoantibodies was confirmed in human EBOV survivors. Overall, this study supports the concept that autoimmunity is a causative parameter that contributes to the various illnesses observed in EBOV survivors.
Activation volume of selected liquid crystals in the density scaling regime
Authors: Grzybowski A. , Urban S. , Mroz S. , Paluch M.
Published: February 2017

In this paper, we demonstrate and thoroughly analyze the activation volumetric properties of selected liquid crystals in the nematic and crystalline E phases in comparison with those reported for glass-forming liquids. In the analysis, we have employed and evaluated two entropic models (based on either total or configurational entropies) to describe the longitudinal relaxation times of the liquid crystals in the density scaling regime. In this study, we have also exploited two equations of state: volumetric and activation volumetric ones. As a result, we have established that the activation volumetric properties of the selected liquid crystals are quite opposite to such typical properties of glass-forming materials, i.e., the activation volume decreases and the isothermal bulk modulus increases when a liquid crystal is isothermally compressed. Using the model based on the configurational entropy, we suggest that the increasing pressure dependences of the activation volume in isothermal conditions and the negative curvature of the pressure dependences of isothermal longitudinal relaxation times can be related to the formation of antiparallel doublets in the examined liquid crystals. A similar pressure effect on relaxation dynamics may be also observed for other material groups in case of systems, the molecules of which form some supramolecular structures.
Bile acid homeostasis controls CAR signaling pathways in mouse testis through FXRalpha
Authors: Martinot Emmanuelle , Baptissart Marine , Véga Aurélie , Sèdes Lauriane , Rouaisnel Betty , Vaz Fred , Saru Jean-Paul , de Haze Angélique , Baron Silvère , Caira Françoise , Beaudoin Claude , Volle David H.
Published: February 2017

Bile acids (BAs) are molecules with endocrine activities controlling several physiological functions such as immunity, glucose homeostasis, testicular physiology and male fertility. The role of the nuclear BA receptor FXRα in the control of BA homeostasis has been well characterized. The present study shows that testis synthetize BAs. We demonstrate that mice invalidated for the gene encoding FXRα have altered BA homeostasis in both liver and testis. In the absence of FXRα, BA exposure differently alters hepatic and testicular expression of genes involved in BA synthesis. Interestingly, Fxrα-/- males fed a diet supplemented with BAs show alterations of testicular physiology and sperm production. This phenotype was correlated with the altered testicular BA homeostasis and the production of intermediate metabolites of BAs which led to the modulation of CAR signaling pathways within the testis. The role of the CAR signaling pathways within testis was validated using specific CAR agonist (TCPOBOP) and inverse agonist (androstanol) that respectively inhibited or reproduced the phenotype observed in Fxrα-/- males fed BA-diet. These data open interesting perspectives to better define how BA homeostasis contributes to physiological or pathophysiological conditions via the modulation of CAR activity.
Genomic insights into the population structure and history of the Irish Travellers
Authors: Gilbert Edmund , Carmi Shai , Ennis Sean , Wilson James F. , Cavalleri Gianpiero L.
Published: February 2017

The Irish Travellers are a population with a history of nomadism; consanguineous unions are common and they are socially isolated from the surrounding, ‘settled’ Irish people. Low-resolution genetic analysis suggests a common Irish origin between the settled and the Traveller populations. What is not known, however, is the extent of population structure within the Irish Travellers, the time of divergence from the general Irish population, or the extent of autozygosity. Using a sample of 50 Irish Travellers, 143 European Roma, 2232 settled Irish, 2039 British and 6255 European or world-wide individuals, we demonstrate evidence for population substructure within the Irish Traveller population, and estimate a time of divergence before the Great Famine of 1845–1852. We quantify the high levels of autozygosity, which are comparable to levels previously described in Orcadian 1st/2nd cousin offspring, and finally show the Irish Traveller population has no particular genetic links to the European Roma. The levels of autozygosity and distinct Irish origins have implications for disease mapping within Ireland, while the population structure and divergence inform on social history.
Indispensable role of Mdm2/p53 interaction during the embryonic and postnatal inner ear development
Authors: Laos M. , Sulg M. , Herranen A. , Anttonen T. , Pirvola U.
Published: February 2017

p53 is a key component of a signaling network that protects cells against various stresses. As excess p53 is detrimental to cells, its levels are tightly controlled by several mechanisms. The E3 ubiquitin ligase Mdm2 is a major negative regulator of p53. The significance of balanced p53 levels in normal tissues, at different stages of lifetime, is poorly understood. We have studiedin vivohow the disruption of Mdm2/p53 interaction affects the early-embryonic otic progenitor cells and their descendants, the auditory supporting cells and hair cells. We found that p53 accumulation, as a consequence ofMdm2abrogation, is lethal to both proliferative progenitors and non-proliferating, differentiating cells. The sensitivity of postmitotic supporting cells to excess p53 decreases along maturation, suggesting that maturation-related mechanisms limit p53′s transcriptional activity towards pro-apoptotic factors. We have also investigatedin vitrowhether p53 restricts supporting cell’s regenerative capacity. Unlike in several other regenerative cellular models,p53inactivation did not alter supporting cell’s proliferative quiescence nor transdifferentiation capacity. Altogether, the postmitotic status of developing hair cells and supporting cells does not confer protection against the detrimental effects of p53 upregulation. These findings might be linked to auditory disturbances observed in developmental syndromes with inappropriate p53 upregulation.