bluuebunny/crossref_metadata_2025 huggingface dataset:
Millimeter VLBI observations of Sgr A* with KaVA and KVN
Authors: Zhao G.-Y. , Kino M. , Cho I.-J. , Akiyama K. , Sohn B. W. , Jung T. , Algaba J. C. , Hada K. , Hagiwara Y. , Hodgson J. , Honma M. , Kawaguchi N. , Koyama S. , Lee J. A. , Lee T. , Niinuma K. , Oh J. , Park J.-H. , Ro H. , Sawada-Satoh S. , Tazaki F. , Trippe S. , Wajima K. , Yoo H.
Published: February 2017

We present recent observation results of Sgr A* at millimeter obtained with VLBI arrays in Korea and Japan.

7 mm monitoring of Sgr A* is part of our AGN large project. The results at 7 epochs during 2013-2014, including high resolution maps, flux density and two-dimensional size measurements are presented. The source shows no significant variation in flux and structure related to the G2 encounter in 2014. According to recent MHD simulations by kawashimaet al., flux and magnetic field energy can be expected to increase several years after the encounter; We will keep our monitoring in order to test this prediction.

Astrometric observations of Sgr A* were performed in 2015 at 7 and 3.5 millimeter simultaneously. Source-frequency phase referencing was applied and a combined ”core-shift” of Sgr A* and a nearby calibrator was measured. Future observations and analysis are necessary to determine the core-shift in each source.
Can we infer the past activity of M31⋆ as we do for Sgr A⋆?
Authors: Clavel Maïca , Terrier Régis , Goldwurm Andrea , Morris Mark R. , Ponti Gabriele
Published: February 2017

The history of supermassive black holes’ activity can be partly constrained by monitoring the diffuse X-ray emission possibly created by the echoes of past events propagating through the molecular clouds of their respective environments. In particular, using this method we have demonstrated that our Galaxy’s supermassive black hole, Sgr A⋆, has experienced multiple periods of higher activity in the last centuries, likely due to several short but very energetic events, and we now investigate the possibility of studying the past activity of other supermassive black holes by applying the same method to M31⋆. We set strong constraints on putative phase transitions of this more distant galactic nucleus but the existence of short events such as the ones observed in the Galactic center cannot be assessed with the upper limits we derived.
Imperial Thirst: Water and Colonial Administration in Algeria, 1840–1880
Authors: Cutler Brock
Published: February 2017

“Water,” wrote the mayor’s council late in the nineteenth century, “is the only thing holding Algiers back from expanding its glory as the queen of African cities.” Paris uses 240 liters of water per person per day, it reported; New York, Philadelphia and Chicago 400 liters. Algiers could only muster a meager 60 liters per day per person, far below the levels necessary to feed a population, fill wells, and scrub a city of its toxins. For over half a century, the council reported, Algiers had thirsted after the clean water necessary to make it a great city. If the French were to make Algiers truly modern, they would need to solve this vexing problem of water.

Thus the council summed up one of the ongoing challenges in continuing settler colonialism in Algeria. Environmental projects—battling epidemic disease, drought, locust invasions, and providing/establishing hydraulic control—became important factors in the rise and expansion of the colonial state. In the midst of a crippling environmental disaster, water—access to fresh water for drinking, controlling agricultural infrastructure, and ensuring cities were “hygienic”—became a site of contention in the creation of the modern state. In this paper I will briefly examine how the physical control of water resources, along with discourses about modernity and modern governance, contributed to the expansion of the colonial state by the end of the 1860s.
Out of Africa: Tocqueville’s Imperial Voyages
Authors: Welch Cheryl B.
Published: February 2017

As Tocqueville’s writings on empire have become more available in translation, and as both Anglophone and Francophone political theorists have begun to grapple with the transnational aspects of democratic theory, scholars have increasingly puzzled over the apparent dissonance between Tocqueville’s liberal and imperial voices. How can his dedication to human freedom co-exist with his embrace of permanent colonial domination in Algeria? This essay attempts to contextualize this paradox in Tocqueville’s thought without turning historical context into an apologia.
The Mediterranean as a Borderland
Authors: Darling Linda T.
Published: February 2017

A useful paradigm for studying Mediterranean and world history is the concept behind a course I teach, “The Mediterranean as a Borderland.” The paradigm of the borderland was generated by policymakers and social scientists studying the American Southwest and developed for the field of history by Oscar Martinez at the University of Arizona. Arizona is in the borderland, the region close to the border between the United States and Mexico where the influence of Mexico can be directly felt. There is of course an equivalent region on the other side in Mexico that is directly influenced by its proximity to the United States. These two regions together comprise the borderland, and they are in many ways more similar to each other than either is to the rest of the nation it belongs to. Unlike the border itself, which divides one country from another, the borderland is the area where the two societies meet and overlap. The Mediterranean Sea is often seen as a border between Christian and Muslim civilizations to the north and south. It can therefore be studied as a borderland, the region where the two overlap. Such a study highlights similarities, influences, and exchanges rather than differences and oppositions; it forms a necessary corrective to today’s emphasis on the “clash of civilizations.” This paper gives a historiography of the borderland paradigm and its application in the Mediterranean, and compares it with the closely related concept of the frontier.
Jan Hasištejnský z Lobkovic: A Fifteenth-Century Czech Traveler to the Mediterranean World
Authors: Lisy-Wagner Laura
Published: February 2017

In 1493, a Czech nobleman named Jan Hasištejnský z Lobkovic embarked on a pilgrimage to Jerusalem. As nearly all Central European pilgrims did, he traveled south through the Tyrol to Venice and joined a large, multinational group there before setting out across the Mediterranean. He remained nearly a month in Venice, meeting prominent political figures, visiting churches and cloisters, and admiring the realism of the painting and sculpture of the Venetianquattrocento. Among all the other marvels of Venice that he describes in his 1505 travelogue is the memory of his day trip to the island of Murano. “In this little town,” he writes, “there are, I think, close to seventy artisans or more, and all are glass makers.” He describes some of the fine works that he saw there, and eagerly adds, “and there is always a great quantity of these various things completed, so that whoever arrives wants to buy something of it.” In this moment, the fifteenth-century tourist is not that far removed from his counterpart in the twenty-first century.
Kings, Queens, Rooks and Pawns: Towards Deciphering the Lebanese Political Chessboard
Authors: Bordenkircher Eric
Published: February 2017

The delineation and comprehension of the Lebanese political map can often be an exercise in futility. On almost any given day, one can just scour the headlines of the Lebanese press and observe the presentation of Lebanese domestic politics in the context of regional/extra-regional developments or its literal interaction with external actors/states. For example, on 6 May 2010, two of the leading Lebanese dailies,As-SafirandAd-Diyar, carried distinct front page headlines which captured this reality. The leadingAs-Safirheadline proclaimed, “The return of Junblatt from Riyadh: Mutually confirms the importance of peace with Syria.” The leadingAd-Diyarheadline stated, “Municipal Elections move forward under the auspices of a Syrian-Saudi-French understanding.“
A Systematic Review of the Literature Linking Neural Correlates of	Feedback Processing to Learning
Authors: Dion Jan-Sébastien , Restrepo Gérardo
Published: February 2017

Abstract. Learning from errors and feedback is an important topic in the Education Sciences as it relates as much to student achievement, teacher development, and learning in general. Its ramifications connect with reflective practice, inhibition of spontaneous and erroneous answers, conceptual change, self-regulated learning, assessment, and metacognition. Research in education has studied the use of feedback from different perspectives (e.g., cognitivism, behaviorism, socioculturalism, constructivism) but has rarely considered the way the brain processes feedback for learning. Therefore, this article reviews the scientific literature linking neural correlates of feedback processing to general or specific learning outcomes, published from 2005 to 2015. From a total of 229 search results, 30 scientific publications were selected according to predefined selection criteria.
The Effect of a Prospected Reward on Semantic	Processing
Authors: van der Ven Sanne H. G. , van Touw Sven A. C. , van Hoogmoed Anne H. , Janssen Eva M. , Leseman Paul P. M.
Published: February 2017

Abstract. Promised rewards are often used in education to stimulate learning behaviour. The present study tested whether a reward prospect affects semantic processing and recall of learned materials. Thirty-nine females participated in an electroencephalogram (EEG) task measuring semantic processing using the N400 effect. After that, they completed a cued recall test of the task materials. Before the EEG task, half of the participants (n = 20) were told that financial compensation would increase with each correct answer (reward prospect condition). The other half (n = 19) were told that financial compensation was fixed (control condition). Participants in the reward prospect condition showed an N400 effect that was more spread over the (left) frontal areas, and showed better recall than participants in the control condition. An achievement-related reward prospect alters semantic processing and improves retention of learned material. Whether improved retention benefits learning in longer term needs further study.
Neuroscience-Based Approaches to Teaching Students on the Autism	Spectrum
Authors: Cockerham Debbie , Malaia Evie
Published: February 2017

Abstract. An understanding of the relationship between emotions, cognition, and learning can provide insight into learning needs for children with autism spectrum disorder (ASD). This article discusses current research and new theories on ASD from three different perspectives: the behavioral sciences, neuroscience, and education. The rapid increase of ASD diagnoses in children worldwide, and an understanding of autism as one of the developmental disorders affecting a spectrum of neural networks in a growing brain, indicates that educational implications from the combined insights may strengthen the development of strategies and interventions not only for ASD individuals, but for neurotypical children as well.
Behavioral and Neural Effects of Game-Based Learning on Improving	Computational Fluency With Numbers
Authors: Çakır Murat Perit , Çakır Nur Akkuş , Ayaz Hasan , Lee Frank J.
Published: February 2017

Abstract. This study examines the short-term behavioral and neural effects of an educational mobile game called MathDash on computational fluency. A portable functional near-infrared spectroscopy (fNIR) device was used to monitor changes in the prefrontal cortices of middle school students due to game-based training. Our aim is to explore changes in neural activity at regions in the prefrontal cortex associated with the management of working memory and attentional resources due to arithmetic training with MathDash. Overall, our results indicated that playing MathDash for a short duration of time elicited behavioral improvements as well as functional changes in bilateral dorsolateral prefrontal cortex.
How Mars Got Its Layered North Polar Cap
Authors: Underwood Emily
Published: February 2017

Orbital wobbling shaped the dome of ice and dust at the planet's north pole.
Microenvironment-derived factors driving metastatic plasticity in melanoma
Authors: Kim Isabella S. , Heilmann Silja , Kansler Emily R. , Zhang Yan , Zimmer Milena , Ratnakumar Kajan , Bowman Robert L. , Simon-Vermot Theresa , Fennell Myles , Garippa Ralph , Lu Liang , Lee William , Hollmann Travis , Xavier Joao B. , White Richard M.
Published: February 2017

Cellular plasticity is a state in which cancer cells exist along a reversible phenotypic spectrum, and underlies key traits such as drug resistance and metastasis. Melanoma plasticity is linked to phenotype switching, where the microenvironment induces switches between invasive/MITFLO versus proliferative/MITFHI states. Since MITF also induces pigmentation, we hypothesize that macrometastatic success should be favoured by microenvironments that induce a MITFHI/differentiated/proliferative state. Zebrafish imaging demonstrates that after extravasation, melanoma cells become pigmented and enact a gene expression program of melanocyte differentiation. We screened for microenvironmental factors leading to phenotype switching, and find that EDN3 induces a state that is both proliferative and differentiated. CRISPR-mediated inactivation of EDN3, or its synthetic enzyme ECE2, from the microenvironment abrogates phenotype switching and increases animal survival. These results demonstrate that after metastatic dissemination, the microenvironment provides signals to promote phenotype switching and provide proof that targeting tumour cell plasticity is a viable therapeutic opportunity.
Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination
Authors: Zheng Yu , Miyamoto David T. , Wittner Ben S. , Sullivan James P. , Aceto Nicola , Jordan Nicole Vincent , Yu Min , Karabacak Nezihi Murat , Comaills Valentine , Morris Robert , Desai Rushil , Desai Niyati , Emmons Erin , Milner John D. , Lee Richard J. , Wu Chin-Lee , Sequist Lecia V. , Haas Wilhelm , Ting David T. , Toner Mehmet , Ramaswamy Sridhar , Maheswaran Shyamala , Haber Daniel A.
Published: February 2017

Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4. Depletion of HBB in CTC-derived cultures has minimal effects on primary tumour growth, but it greatly increases apoptosis following ROS exposure, and dramatically reduces CTC-derived lung metastases. These effects are reversed by the anti-oxidant N-Acetyl Cysteine. Conversely, overexpression of HBB is sufficient to suppress intracellular ROS within CTCs. Altogether, these observations suggest that β-globin is selectively deregulated in cancer cells, mediating a cytoprotective effect during blood-borne metastasis.
Slow-light-enhanced energy efficiency for graphene microheaters on silicon photonic crystal waveguides
Authors: Yan Siqi , Zhu Xiaolong , Frandsen Lars Hagedorn , Xiao Sanshui , Mortensen N. Asger , Dong Jianji , Ding Yunhong
Published: February 2017

Slow light has been widely utilized to obtain enhanced nonlinearities, enhanced spontaneous emissions and increased phase shifts owing to its ability to promote light–matter interactions. By incorporating a graphene on a slow-light silicon photonic crystal waveguide, here we experimentally demonstrate an energy-efficient graphene microheater with a tuning efficiency of 1.07 nmmW−1 and power consumption per free spectral range of 3.99 mW. The rise and decay times (10–90%) are only 750 and 525 ns, which, to the best of our knowledge, are the fastest reported response times for microheaters in silicon photonics. The corresponding figure of merit of the device is 2.543 nW s, one order of magnitude better than results reported in previous studies. The influence of the length and shape of the graphene heater to the tuning efficiency is further investigated, providing valuable guidelines for enhancing the tuning efficiency of the graphene microheater.
Using graphene networks to build bioinspired self-monitoring ceramics
Authors: Picot Olivier T. , Rocha Victoria G. , Ferraro Claudio , Ni Na , D’Elia Eleonora , Meille Sylvain , Chevalier Jerome , Saunders Theo , Peijs Ton , Reece Mike J. , Saiz Eduardo
Published: February 2017

The properties of graphene open new opportunities for the fabrication of composites exhibiting unique structural and functional capabilities. However, to achieve this goal we should build materials with carefully designed architectures. Here, we describe the fabrication of ceramic-graphene composites by combining graphene foams with pre-ceramic polymers and spark plasma sintering. The result is a material containing an interconnected, microscopic network of very thin (20–30 nm), electrically conductive, carbon interfaces. This network generates electrical conductivities up to two orders of magnitude higher than those of other ceramics with similar graphene or carbon nanotube contents and can be used to monitor ‘in situ’ structural integrity. In addition, it directs crack propagation, promoting stable crack growth and increasing the fracture resistance by an order of magnitude. These results demonstrate that the rational integration of nanomaterials could be a fruitful path towards building composites combining unique mechanical and functional performances.
Tunable thermal expansion in framework materials through redox intercalation
Authors: Chen Jun , Gao Qilong , Sanson Andrea , Jiang Xingxing , Huang Qingzhen , Carnera Alberto , Rodriguez Clara Guglieri , Olivi Luca , Wang Lei , Hu Lei , Lin Kun , Ren Yang , Lin Zheshuai , Wang Cong , Gu Lin , Deng Jinxia , Attfield J. Paul , Xing Xianran
Published: February 2017

Thermal expansion properties of solids are of fundamental interest and control of thermal expansion is important for practical applications but can be difficult to achieve. Many framework-type materials show negative thermal expansion when internal cages are empty but positive thermal expansion when additional atoms or molecules fill internal voids present. Here we show that redox intercalation offers an effective method to control thermal expansion from positive to zero to negative by insertion of Li ions into the simple negative thermal expansion framework material ScF3, doped with 10% Fe to enable reduction. The small concentration of intercalated Li ions has a strong influence through steric hindrance of transverse fluoride ion vibrations, which directly controls the thermal expansion. Redox intercalation of guest ions is thus likely to be a general and effective method for controlling thermal expansion in the many known framework materials with phonon-driven negative thermal expansion.
On the post-glacial spread of human commensal Arabidopsis thaliana
Authors: Lee Cheng-Ruei , Svardal Hannes , Farlow Ashley , Exposito-Alonso Moises , Ding Wei , Novikova Polina , Alonso-Blanco Carlos , Weigel Detlef , Nordborg Magnus
Published: February 2017

Recent work has shown that Arabidopsis thaliana contains genetic groups originating from different ice age refugia, with one particular group comprising over 95% of the current worldwide population. In Europe, relicts of other groups can be found in local populations along the Mediterranean Sea. Here we provide evidence that these ‘relicts’ occupied post-glacial Eurasia first and were later replaced by the invading ‘non-relicts’, which expanded through the east–west axis of Eurasia, leaving traces of admixture in the north and south of the species range. The non-relict expansion was likely associated with human activity and led to a demographic replacement similar to what occurred in humans. Introgressed genomic regions from relicts are associated with flowering time and enriched for genes associated with environmental conditions, such as root cap development or metal ion trans-membrane transport, which suggest that admixture with locally adapted relicts helped the non-relicts colonize new habitats.
In situ click chemistry generation of cyclooxygenase-2 inhibitors
Authors: Bhardwaj Atul , Kaur Jatinder , Wuest Melinda , Wuest Frank
Published: February 2017

Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors.
Repeated evolution of soldier sub-castes suggests parasitism drives social complexity in stingless bees
Authors: Grüter Christoph , Segers Francisca H. I. D. , Menezes Cristiano , Vollet-Neto Ayrton , Falcón Tiago , von Zuben Lucas , Bitondi Márcia M. G. , Nascimento Fabio S. , Almeida Eduardo A. B.
Published: February 2017

The differentiation of workers into morphological castes represents an important evolutionary innovation that is thought to improve division of labor in insect societies. Given the potential benefits of task-related worker differentiation, it is puzzling that physical worker castes, such as soldiers, are extremely rare in social bees and absent in wasps. Following the recent discovery of soldiers in a stingless bee, we studied the occurrence of worker differentiation in 28 stingless bee species from Brazil and found that several species have specialized soldiers for colony defence. Our results reveal that worker differentiation evolved repeatedly during the last ~ 25 million years and coincided with the emergence of parasitic robber bees, a major threat to many stingless bee species. Furthermore, our data suggest that these robbers are a driving force behind the evolution of worker differentiation as targets of robber bees are four times more likely to have nest guards of increased size than non-targets. These findings reveal unexpected diversity in the social organization of stingless bees.
Asymptotic Gaussian law for noninteracting indistinguishable particles in random networks
Authors: Shchesnovich Valery S.
Published: February 2017

For N indistinguishable bosons or fermions impinged on a M-port Haar-random unitary network the average probability to count n1, … n
r
particles in a small number r ≪ N of binned-together output ports takes a Gaussian form as N ≫ 1. The discovered Gaussian asymptotic law is the well-known asymptotic law for distinguishable particles, governed by a multinomial distribution, modified by the quantum statistics with stronger effect for greater particle density N/M. Furthermore, it is shown that the same Gaussian law is the asymptotic form of the probability to count particles at the output bins of a fixed multiport with the averaging performed over all possible configurations of the particles in the input ports. In the limit N → ∞, the average counting probability for indistinguishable bosons, fermions, and distinguishable particles differs only at a non-vanishing particle density N/M and only for a singular binning K/M → 1, where K output ports belong to a single bin.
Correction: Corrigendum: Vesicle Size Regulates Nanotube Formation in the Cell
Authors: Su Qian Peter , Du Wanqing , Ji Qinghua , Xue Boxin , Jiang Dong , Zhu Yueyao , Ren He , Zhang Chuanmao , Lou Jizhong , Yu Li , Sun Yujie
Published: February 2017

Scientific Reports 6: Article number: 24002; published online: 07 April 2016; updated: 09 February 2017 He Ren and Chuanmao Zhang were omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, as well as the Supplementary Information that now accompanies the Article.
Associations between polymorphisms of the ADIPOQ gene and hypertension risk: a systematic and meta-analysis
Authors: Fan Weina , Qu Xiaowei , Li Jing , Wang Xingning , Bai Yanping , Cao Qingmei , Ma Liqun , Zhou Xiaoyao , Zhu Wei , Liu Wei , Ma Qiang
Published: February 2017

ADIPOQ gene polymorphisms have been indicated to be associated with hypertension; however, published studies have reported inconsistent results. Eligible studies were retrieved by searching the PubMed, Embase and China National Knowledge Infrastructure databases. The case group consisted of patients with hypertension, and the control group consisted of subjects with normal blood pressure. Based on eleven published articles, involving 4837 cases and 5618 controls, the pooled results from rs2241766 polymorphism showed increased risk in the allelic model (G VS T: OR = 1.16, 95%CI = 1.06–1.27), recessive model (GG VS GT + TT: OR = 1.34, 95%CI = 1.10–1.63), dominant model (GG + GT VS TT: OR = 1.15, 95%CI = 1.02–1.30) and homozygote model (GG VS TT: OR = 1.38, 95%CI = 1.21–1.69). In addition, rs266729 polymorphism showed increased risk for hypertension in the recessive model (GG VS GC + CC: OR = 1.43, 95%CI = 1.02–2.01). In the Caucasian subgroup, rs1501299 polymorphism showed decreased risk of hypertension in the allelic model (T VS G: OR = 0.75, 95%CI = 0.58–0.97), dominant model (TT + TG VS GG: OR = 0.83, 95%CI = 0.71–0.98) and heterozygote model (TG VS GG: OR = 0.82, 95%CI = 0.68–0.99). The rs2241766 polymorphism was associated with a significant increase in hypertension risk based on our analysis. Moreover, an increased risk of rs266729 in hypertension patients was also detected. Our meta-analysis suggests that the rs1501299 polymorphism may play a protective role in hypertension in Caucasian subgroup; however, this finding requires further study.
Novel concept for neutron detection: proportional counter filled with 10B nanoparticle aerosol
Authors: Amaro F. D. , Monteiro C. M. B. , dos Santos J. M. F. , Antognini A.
Published: February 2017

The high neutron detection efficiency, good gamma-ray discrimination and non-toxicity of 3He made of proportional counters filled with this gas the obvious choice for neutron detection, particularly in radiation portal monitors (RPM), used to control the illicit transport of nuclear material, of which neutron detectors are key components. 3He is very rare and during the last decade this gas has become increasingly difficult to acquire. With the exception of BF3, which is toxic, no other gas can be used for neutron detection in proportional counters. We present an alternative where the 3He atoms are replaced by nanoparticles made of another neutron sensitive material, 10B. The particles are dispersed in a gaseous volume, forming an aerosol with neutron sensitive properties. A proportional counter filled with such aerosol was exposed to a thermal neutron beam and the recorded response indicates that the neutrons have interacted with the particles in the aerosol. This original technique, which transforms a standard proportional gas mixture into a neutron sensitive aerosol, is a breakthrough in the field of radiation detection and has the potential to become an alternative to the use of 3He in proportional counters.
Mitochondria play an important role in the cell proliferation suppressing activity of berberine
Authors: Yan Xiao-Jin , Yu Xuan , Wang Xin-Pei , Jiang Jing-Fei , Yuan Zhi-Yi , Lu Xi , Lei Fan , Xing Dong-Ming
Published: February 2017

After being studied for approximately a century, berberine (BBR) has been found to act on various targets and pathways. A great challenge in the pharmacological analysis of BBR at present is to identify which target(s) plays a decisive role. In the study described herein, a rescue experiment was designed to show the important role of mitochondria in BBR activity. A toxic dose of BBR was applied to inhibit cell proliferation and mitochondrial activity, then α-ketobutyrate (AKB), an analogue of pyruvate that serves only as an electron receptor of NADH, was proven to partially restore cell proliferation. However, mitochondrial morphology damage and TCA cycle suppression were not recovered by AKB. As the AKB just help to regenerate NAD+, which is make up for part function of mitochondrial, the recovered cell proliferation stands for the contribution of mitochondria to the activity of BBR. Our results also indicate that BBR suppresses tumour growth and reduces energy charge and mitochondrial DNA (mtDNA) copy number in a HepG2 xenograft model. In summary, our study suggests that mitochondria play an important role in BBR activity regarding tumour cell proliferation and metabolism.
New 2D diffraction model and its applications to terahertz parallel-plate waveguide power splitters
Authors: Zhang Fan , Song Kaijun , Fan Yong
Published: February 2017

A two-dimensional (2D) diffraction model for the calculation of the diffraction field in 2D space and its applications to terahertz parallel-plate waveguide power splitters are proposed in this paper. Compared with the Huygens-Fresnel principle in three-dimensional (3D) space, the proposed model provides an approximate analytical expression to calculate the diffraction field in 2D space. The diffraction filed is regarded as the superposition integral in 2D space. The calculated results obtained from the proposed diffraction model agree well with the ones by software HFSS based on the element method (FEM). Based on the proposed 2D diffraction model, two parallel-plate waveguide power splitters are presented. The splitters consist of a transmitting horn antenna, reflectors, and a receiving antenna array. The reflector is cylindrical parabolic with superimposed surface relief to efficiently couple the transmitted wave into the receiving antenna array. The reflector is applied as computer-generated holograms to match the transformed field to the receiving antenna aperture field. The power splitters were optimized by a modified real-coded genetic algorithm. The computed results of the splitters agreed well with the ones obtained by software HFSS verify the novel design method for power splitter, which shows good applied prospects of the proposed 2D diffraction model.
Self-Polarizing Microswimmers in Active Density Waves
Authors: Geiseler Alexander , Hänggi Peter , Marchesoni Fabio
Published: February 2017

An artificial microswimmer drifts in response to spatio-temporal modulations of an activating suspension medium. We consider two competing mechanisms capable of influencing its tactic response: angular fluctuations, which help it explore its surroundings and thus diffuse faster toward more active regions, and self-polarization, a mechanism inherent to self-propulsion, which tends to orient the swimmer’s velocity parallel or antiparallel to the local activation gradients. We investigate, both numerically and analytically, the combined action of such two mechanisms. By determining their relative magnitude, we characterize the selective transport of artificial microswimmers in inhomogeneous activating media.
Natriuretic Peptide Receptor B modulates the proliferation of the cardiac cells expressing the Stem Cell Antigen-1
Authors: Rignault-Clerc Stéphanie , Bielmann Christelle , Liaudet Lucas , Waeber Bernard , Feihl François , Rosenblatt-Velin Nathalie
Published: February 2017

Brain Natriuretic Peptide (BNP) injections in adult “healthy” or infarcted mice led to increased number of non-myocyte cells (NMCs) expressing the nuclear transcription factor Nkx2.5. The aim of this study was to identify the nature of the cells able to respond to BNP as well as the signaling pathway involved. BNP treatment of neonatal mouse NMCs stimulated Sca-1+ cell proliferation. The Sca-1+ cells were characterized as being a mixed cell population involving fibroblasts and multipotent precursor cells. Thus, BNP treatment led also to increased number of Sca-1+ cells expressing Nkx2.5, in Sca-1+ cell cultures in vitro and in vivo, in the hearts of neonatal and adult infarcted mice. Whereas BNP induced Sca-1+ cell proliferation via NPR-B receptor and protein kinase G activation, CNP stimulated Sca-1+ cell proliferation via NPR-B and a PKG-independent mechanism. We highlighted here a new role for the natriuretic peptide receptor B which was identified as a target able to modulate the proliferation of the Sca-1+ cells. The involvement of NPR-B signaling in heart regeneration has, however, to be further investigated.
Nanoscale diffusion in the synaptic cleft and beyond measured with time-resolved fluorescence anisotropy imaging
Authors: Zheng Kaiyu , Jensen Thomas P. , Savtchenko Leonid P. , Levitt James A. , Suhling Klaus , Rusakov Dmitri A.
Published: February 2017

Neural activity relies on molecular diffusion within nanoscopic spaces outside and inside nerve cells, such as synaptic clefts or dendritic spines. Measuring diffusion on this small scale in situ has not hitherto been possible, yet this knowledge is critical for understanding the dynamics of molecular events and electric currents that shape physiological signals throughout the brain. Here we advance time-resolved fluorescence anisotropy imaging combined with two-photon excitation microscopy to map nanoscale diffusivity in ex vivo brain slices. We find that in the brain interstitial gaps small molecules move on average ~30% slower than in a free medium whereas inside neuronal dendrites this retardation is ~70%. In the synaptic cleft free nanodiffusion is decelerated by ~46%. These quantities provide previously unattainable basic constrains for the receptor actions of released neurotransmitters, the electrical conductance of the brain interstitial space and the limiting rate of molecular interactions or conformational changes in the synaptic microenvironment.
Protective effect of mangiferin on myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats: role of AGE-RAGE/MAPK pathways
Authors: Suchal Kapil , Malik Salma , Khan Sana Irfan , Malhotra Rajiv Kumar , Goyal Sameer N. , Bhatia Jagriti , Kumari Santosh , Ojha Shreesh , Arya Dharamvir Singh
Published: February 2017

Hyperglycemia induced advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) activation is thought to involve in the development of cardiovascular disease in diabetics. Activation of AGE-RAGE axis results in the oxidative stress and inflammation. Mangiferin is found in the bark of mango tree and is known to treat diseases owing to its various biological activities. Thus, this study was designed to evaluate the effect of mangiferin in ischemia-reperfusion (IR) induced myocardial injury in diabetic rats. A single injection of STZ (70 mg/kg; i.p.) was injected to male albino Wistar rats to induce diabetes. After confirmation of diabetes, rats were administered vehicle (2 ml/kg; i.p.) and mangiferin (40 mg/kg; i.p.) for 28 days. On 28th day, left anterior descending coronary artery was ligated for 45 min and then reperfused for 60 min. Mangiferin treatment significantly improved cardiac function, restored antioxidant status, reduced inflammation, apoptosis and maintained myocardial architecture. Furthermore, mangiferin significantly inhibited the activation of AGE-RAGE axis, c-Jun N-terminal kinase (JNK) and p38 and increased the expression of extracellular regulated kinase 1/2 (ERK1/2) in the myocardium. Thus, mangiferin attenuated IR injury in diabetic rats by modulation of AGE-RAGE/MAPK pathways which further prevented oxidative stress, inflammation and apoptosis in the myocardium.
Differences in the transcriptome of medullary thyroid cancer regarding the status and type of RET gene mutations
Authors: Oczko-Wojciechowska Malgorzata , Swierniak Michal , Krajewska Jolanta , Kowalska Malgorzata , Kowal Monika , Stokowy Tomasz , Wojtas Bartosz , Rusinek Dagmara , Pawlaczek Agnieszka , Czarniecka Agnieszka , Szpak-Ulczok Sylwia , Gawlik Tomasz , Chmielik Ewa , Tyszkiewicz Tomasz , Nikiel Barbara , Lange Dariusz , Jarzab Michal , Wiench Malgorzata , Jarzab Barbara
Published: February 2017

Medullary thyroid cancer (MTC) can be caused by germline mutations of theRETproto-oncogene or occurs as a sporadic form. It is well known thatRETmutations affecting the cysteine-rich region of the protein (MEN2A-like mutations) are correlated with different phenotypes than those in the kinase domain (MEN2B-like mutations). Our aim was to analyse the whole-gene expression profile of MTC with regard to the type ofRETgene mutation and the cancer genetic background (hereditary vs sporadic). We studied 86 MTC samples. We demonstrated that there were no distinct differences in the gene expression profiles of hereditary and sporadic MTCs. This suggests a homogeneous nature of MTC. We also noticed that the site of theRETgene mutation slightly influenced the gene expression profile of MTC. We found a significant association between the localization ofRETmutations and the expression of three genes:NNAT(suggested to be a tumour suppressor gene),CDC14B(involved in cell cycle control) andNTRK3(tyrosine receptor kinase that undergoes rearrangement in papillary thyroid cancer). This study suggests that these genes are significantly deregulated in tumours with MEN2A-like and MEN2B-like mutations; however, further investigations are necessary to demonstrate any clinical impact of these findings.
Using information of relatives in genomic prediction to apply effective stratified medicine
Authors: Lee S. Hong , Weerasinghe W. M. Shalanee P. , Wray Naomi R. , Goddard Michael E. , van der Werf Julius H. J.
Published: February 2017

Genomic prediction shows promise for personalised medicine in which diagnosis and treatment are tailored to individuals based on their genetic profiles for complex diseases. We present a theoretical framework to demonstrate that prediction accuracy can be improved by targeting more informative individuals in the data set used to generate the predictors (“discovery sample”) to include those with genetically close relationships with the subjects put forward for risk prediction. Increase of prediction accuracy from closer relationships is achieved under an additive model and does not rely on any family or interaction effects. Using theory, simulations and real data analyses, we show that the predictive accuracy or the area under the receiver operating characteristic curve (AUC) increased exponentially with decreasing effective size (Ne), i.e. when individuals are closely related. For example, with the sample size of discovery set N = 3000, heritability h2 = 0.5 and population prevalence K = 0.1, AUC value approached to 0.9 and the top percentile of the estimated genetic profile scores had 23 times higher proportion of cases than the general population. This suggests that there is considerable room to increase prediction accuracy by using a design that does not exclude closer relationships.
Open-source algorithm for automatic choroid segmentation of OCT volume reconstructions
Authors: Mazzaferri Javier , Beaton Luke , Hounye Gisèle , Sayah Diane N. , Costantino Santiago
Published: February 2017

The use of optical coherence tomography (OCT) to study ocular diseases associated with choroidal physiology is sharply limited by the lack of available automated segmentation tools. Current research largely relies on hand-traced, single B-Scan segmentations because commercially available programs require high quality images, and the existing implementations are closed, scarce and not freely available. We developed and implemented a robust algorithm for segmenting and quantifying the choroidal layer from 3-dimensional OCT reconstructions. Here, we describe the algorithm, validate and benchmark the results, and provide an open-source implementation under the General Public License for any researcher to use (https://www.mathworks.com/matlabcentral/fileexchange/61275-choroidsegmentation).
Analysis of drought-responsive signalling network in two contrasting rice cultivars using transcriptome-based approach
Authors: Borah Pratikshya , Sharma Eshan , Kaur Amarjot , Chandel Girish , Mohapatra Trilochan , Kapoor Sanjay , Khurana Jitendra P.
Published: February 2017

Traditional cultivars of rice in India exhibit tolerance to drought stress due to their inherent genetic variations. Here we present comparative physiological and transcriptome analyses of two contrasting cultivars, drought tolerant Dhagaddeshi (DD) and susceptible IR20. Microarray analysis revealed several differentially expressed genes (DEGs) exclusively in DD as compared to IR20 seedlings exposed to 3 h drought stress. Physiologically, DD seedlings showed higher cell membrane stability and differential ABA accumulation in response to dehydration, coupled with rapid changes in gene expression. Detailed analyses of metabolic pathways enriched in expression data suggest interplay of ABA dependent along with secondary and redox metabolic networks that activate osmotic and detoxification signalling in DD. By co-localization of DEGs with QTLs from databases or published literature for physiological traits of DD and IR20, candidate genes were identified including those underlying major QTL qDTY1.1 in DD. Further, we identified previously uncharacterized genes from both DD and IR20 under drought conditions including OsWRKY51, OsVP1 and confirmed their expression by qPCR in multiple rice cultivars. OsFBK1 was also functionally validated in susceptible PB1 rice cultivar and Arabidopsis for providing drought tolerance. Some of the DEGs mapped to the known QTLs could thus, be of potential significance for marker-assisted breeding.
Non-patchy strategy for inter-atomic distances from Extended X-ray Absorption Fine Structure
Authors: Xu Gu , Li Guifang , LI Xianya , Liang Yi , Feng Zhechuan
Published: February 2017

Extended X-ray Absorption Fine Structure (EXAFS) has been one of the few structural probes available for crystalline, non-crystalline and even highly disordered specimens. However, the data analysis involves a patchy and tinkering process, including back-and-forth fitting and filtering, leading to ambiguous answers sometimes. Here we try to resolve this long standing problem, to extract the inter-atomic distances from the experimental data by a single step minimization, in order to replace the tedious and tinkering process. The new strategy is built firmly by the mathematical logic, and made straightforward and undeniable. The finding demonstrates that it is possible to break off from the traditional patchy model fitting, and to remove the logical confusion of a priori prediction of the structure to be matched with experimental data, making it a much more powerful technique than the existing methods. The new method is expected to benefit EXAFS users covering all disciplines. Also, it is anticipated that the current work to be the motivation and inspiration to the further efforts.
Correction: Corrigendum: Transcriptomic insights into the allelopathic effects of the garlic allelochemical diallyl disulfide on tomato roots
Authors: Cheng Fang , Cheng Zhi-Hui , Meng Huan-Wen
Published: February 2017

Scientific Reports 6: Article number: 38902; published online: 12 December 2016; updated: 09 February 2017 This article contains a typographical error in the legend of Figure 1 and in the Methods section under the subheading ‘DEGs and function enrichment analyses’, where “log2|FC (ratio of DADS/control)| ≥ 1”
Bigelovin triggered apoptosis in colorectal cancer in vitro and in vivo via upregulating death receptor 5 and reactive oxidative species
Authors: Li Mingyue , Song Li-Hua , Yue Grace Gar-Lee , Lee Julia Kin-Ming , Zhao Li-Mei , Li Lin , Zhou Xunian , Tsui Stephen Kwok-Wing , Ng Simon Siu-Man , Fung Kwok-Pui , Tan Ning-Hua , Lau Clara Bik-San
Published: February 2017

Colorectal cancer (CRC) is the third most prevalent cancer and the third highest cancer-related mortality in the United States. Bigelovin, a sesquiterpene lactone isolated from Inula helianthus aquatica, has been proven to induce apoptosis and exhibit anti-inflammatory and anti-angiogenic activities. However, the effects of bigelovin on CRC and underlying mechanisms have not been explored. The present study demonstrated that bigelovin exhibited potent anti-tumor activities against CRC in vitro and in vivo. Bigelovin suppressed cell proliferation and colony formation and induced apoptosis in human colorectal cancer HT-29 and HCT 116 cells in vitro. Results also revealed that bigelovin activated caspases, caused the G2/M cell cycle arrest and induced DNA damage through up-regulation of death receptor (DR) 5 and increase of ROS. In HCT 116 xenograft model, bigelovin treatment resulted in suppression of tumor growth. Bigelovin at 20 mg/kg showed more significant tumor suppression and less side effects than conventional FOLFOX (containing folinic acid, 5-fluorouracil and oxaliplatin) treatment. In addition, in vivo data confirmed that anti-tumor activity of bigelovin in CRC was through induction of apoptosis by up-regulating DR5 and increasing ROS. In conclusion, these results strongly suggested that bigelovin has potential to be developed as therapeutic agent for CRC patients.
High expression of AKR1B10 predicts low risk of early tumor recurrence in patients with hepatitis B virus-related hepatocellular carcinoma
Authors: Wang Yan-Yan , Qi Lu-Nan , Zhong Jian-Hong , Qin Hong-Gui , Ye Jia-Zhou , Lu Shi-Dong , Ma Liang , Xiang Bang-De , Li Le-Qun , You Xue-Mei
Published: February 2017

To clarify the relationship between aldo-keto reductase family 1 member B10 (AKR1B10) expression and early hepatocellular carcinoma (HCC) recurrence, this study detected AKR1B10 expression in tumor and adjacent non-tumor tissues from 110 patients with hepatitis B virus (HBV)-related HCC underwent liver resection and analyzed its correlations with clinicopathological characteristics and prognosis of these patients. Detected by quantitative reverse transcription polymerase chain reaction, AKR1B10 mRNA expression showed significantly higher in HCC tissues than in adjacent non-tumor tissues, with a low level in normal liver tissues. Similar results was confirmed at the protein level using immunohistochemistry and Western blotting. High AKR1B10 expression was negatively correlated with serum alpha-fetoprotein level and positively correlated with HBV-DNA level. Patients with high AKR1B10 expression had significantly higher disease-free survival than those with low expression within 2 years after liver resection. Multivariate analysis also confirmed high AKR1B10 expression to be a predictor of low risk of early HCC recurrence. In addition, high AKR1B10 expression was found to be a favorable factor of overall survival. These results suggest that AKR1B10 is involved in HBV-related hepatocarcinogenesis, but its high expression could predict low risk of early tumor recurrence in patients with HBV-related HCC after liver resection.