bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards a data‐driven IoT software architecture for smart city utilities
Authors: Simmhan Yogesh , Ravindra Pushkara , Chaturvedi Shilpa , Hegde Malati , Ballamajalu Rashmi
Published: April 2018

The Internet of things (IoT) is emerging as the next big wave of digital presence for billions of devices on the Internet. Smart cities are a practical manifestation of IoT, with the goal of efficient, reliable, and safe delivery of city utilities like water, power, and transport to residents, through their intelligent management. A data‐driven IoT software platform is essential for realizing manageable and sustainable smart utilities and for novel applications to be developed upon them. Here, we propose such service‐oriented software architecture to address 2 key operational activities in a smart utility: the IoT fabric for resource management and the data and application platform for decision‐making. Our design uses Open Web standards and evolving network protocols, cloud and edge resources, and streaming big data platforms. We motivate our design requirements using the smart water management domain; some of these requirements are unique to developing nations. We also validate the architecture within a campus‐scale IoT testbed at the Indian Institute of Science, Bangalore and present our experiences. Our architecture is scalable to a township or city while also generalizable to other smart utility domains. Our experiences serve as a template for other similar efforts, particularly in emerging markets and highlight the gaps and opportunities for a data‐driven IoT software architecture for smart cities.
Proving that the Mind Is Not a Machine?
Authors: Stern Johannes ,   Philosophy Documentation Center
Published: April 2018

This piece continues the tradition of arguments by John Lucas, Roger Penrose and others to the effect that the human mind is not a machine. Kurt Gödel thought that the intensional paradoxes stand in the way of proving that the mind is not a machine. According to Gödel, a successful proof that the mind is not a machine would require a solution to the intensional paradoxes. We provide what might seem to be a partial vindication of Gödel and show that if a particular solution to the intensional paradoxes is adopted, one can indeed give an argument to the effect that the mind is not a machine.
An analytical approach to modeling the stochastic behavior of visco‐elastic materials
Authors: Junker Philipp , Nagel Jan
Published: April 2018

Stochastic fluctuations of material properties, i.e. the elastic constants, result in stochastic fluctuations of the material's response to mechanical loading, i.e. the stresses. In this contribution, we present an analytical approach to the time‐efficient and mathematically accurate modeling of the stochastic behavior of visco‐elastic materials. The material behavior is modeled using a viscous strain as an internal variable whose evolution is described by a differential equation. Since the stochastic material properties enter the evolution equation, a stochastic differential equation has to be treated which renders the problem rather uncomfortable. However, we present a precise investigation of the problem that yields a treatment similar to the deterministic case but resulting in the analytical estimation both of the expectation value and the variance (and standard deviation) of the stresses. A numerical comparison to Monte Carlo simulations proves the reliability of our approach.
Artefacts and Tasks in the Mathematical Preparation of Teachers of Elementary Arithmetic from a Mathematician’s Perspective: A Commentary on Chapter 9
Authors: Hodgson Bernard R.
Published: April 2018

The main focus of this chapter is the mathematical preparation of primary school teachers in relation to the teaching of elementary arithmetic. Comments are offered, from the perspective of a mathematician involved in the education of pre-service teachers, on the importance and variety of artefacts (often of a cultural and historical nature) that can be used to support the learning of whole number arithmetic, as well as on the role played by mathematical tasks in fostering the ‘mathematical message’ that may be conveyed through the artefacts. I will discuss concrete examples taken from an arithmetic course created by my department specifically for prospective primary school teachers, intending so doing to illustrate a crucial observation about artefacts and tasks, namely, that they form an inseparable pair in the teaching and learning of mathematics. This chapter addresses the mathematical preparation of primary school teachers. The learning of arithmetic by actual primary school pupils is not an immediate aim of the work we do with our student teachers, but we claim that many of the artefacts and tasks discussed in our arithmetic course (and in this chapter) can be transferred to pupils – but of course with a necessary adaptation to young children new at such notions.
Structuring Structural Awareness: A Commentary on Chapter 13
Authors: Mason John
Published: April 2018

Expressing generality, by learners, is seen as the heart and soul of school mathematics. To engage successfully requires shifts of attention from recognizing structural relationships in a particular situation to perceiving properties as being instantiated. Some examples of tasks which involve learners in encountering mathematical structure are provided as an extension of Chap. 13, with observations about a learning trajectory concerning the structuring of such tasks. It is proposed that arithmetic is best seen as the study of the structural relations between numbers rather than as a process of getting answers to calculations, which is a sideline. When it becomes the focus, learners merely mimic calculators, badly. The summary from Chap. 13 provides a basis for further suggestions on important directions for further work to bring structural awareness and structural relationships into the core of mathematics teaching.
Social and Cultural Contexts in the Teaching and Learning of Whole Number Arithmetic
Authors: Bartolini Bussi Maria G. , Sun Xu Hua
Published: April 2018

This chapter witnesses the growing importance of understanding the role of the social and cultural context in which the teaching and learning of mathematics is situated, outlining the background to the studies conducted in recent decades. The aim of this chapter is to report on the process that led the IPC to prepare a background information context form for each submitted paper, for the first time in an ICMI Study and, also, in any major international conference. A short analysis of the 66 completed context forms that were received is provided with elaboration and commentary. These data are a convenience sampling based on these submissions, rather than a representation of the population of mathematics educators as a whole. The information provides an ‘insider’ view based on the applicants’ perceptions, rather than a collection of objective data. This contextual information, however, concerns the participants attending the ICMI23 Macao Conference; hence it is important to understand the perceptions of the contributors involved in writing this volume: the data provide outlines of the pre- and primary level schooling cultures and systems within which particular kinds of findings, interventions and outcomes are achieved.
Whole Number Thinking, Learning and Development: A Commentary on Chapter 7
Authors: Nesher Pearla
Published: April 2018

The commentary relates to two main points included in Chap. 7: (a) cardinal and ordinal numbers and (b) patterns and structure. The comments start with mentioning some philosophical approaches to the nature of natural numbers and add the psychological point of view represented by Piaget, that there is no need to differentiate between the cardinal and the ordinal senses of number. Further, the comments support the approach advocated in Chap. 7 about the merits of employing Davydov or Gattegno methods of teaching whole numbers. Several developmental studies about the origins and counting principles are described. Finally, an emphasis is put on the additive structure and the importance of teaching the operation signs as well as the meaning of the equal sign and not merely the numerical outcomes of the operations.
Distribution and stress tolerance of Fimbristylis dichotoma subsp. podocarpa (Cyperaceae) growing in highly acidic solfatara fields
Authors: Yamamoto Akihiro , Wasaki Jun , Funatsu Yuichi , Nakatsubo Takayuki
Published: April 2018

Solfatara fields, areas surrounding fumaroles (volcanic vents) near the hot springs or volcanoes, are characterized by severe environmental conditions such as low soil pH and high aluminum contents. Fimbristylis dichotoma subsp. podocarpa is an endangered plant distributed in solfatara fields of Kyushu, western Japan. This species is known to form stands in sites closed to fumaroles where another solfatara plant Miscanthus sinensis do not colonize. We conducted field survey and culture experiments to test the hypothesis that F. dichotoma has higher tolerance to low pH and high aluminum conditions than M. sinensis, which corresponds to the distribution pattern of the two species. In the study site of Myoban Hot Spring, Oita Prefecture, rhizosphere soils of F. dichotoma showed lower pH and higher aluminum contents than those of M. sinensis. The culture experiment showed that germination of F. dichotoma was not inhibited even at pH 2, whereas significant decline in germination (%) was observed in M. sinensis. However, because of the low germination (%) of F. dichotoma, the values of the two species were similar at pH 2. In the pot culture, seedling growth of M. sinensis was suppressed at the aluminum concentrations tested (400 mg AlCl3 L−1). Conversely, no significant decline in the seedling growth was observed in F. dichotoma at the same aluminum levels. Considering soil conditions in the field, we concluded that that the difference in the tolerance to aluminum between the two species played a significant role in determining their distribution pattern.
A New Information Lens: The Self-concept and Exchange Context as a Means to Understand Information Sensitivity of Anonymous and Personal Identifying Information
Authors: Markos Ereni , Labrecque Lauren I. , Milne George R.
Published: April 2018

Given technological advances, consumers’ sensitivity around personal information is shifting, whereby information once considered innocuous, is now considered more sensitive and warrants more protection. This research examines the self-concept and exchange context as a new lens to understand consumer sensitivity to anonymous and personal identifying information exchange. Two studies examine the role of the public and private self in predicting attitudes toward sharing PII and non-PII items, and across different information exchange contexts. Implications for business and policy makers are provided.
Association of gastroesophageal reflux disease and laryngeal cancer
Authors: Anis Mursalin M. , Razavi Mir‐Muhammad , Xiao Xiao , Soliman Ahmed M.S.
Published: April 2018

Objective

Studies examining the association of reflux disease with the risk of developing laryngeal cancer have both proven and disproven the null hypothesis.

Methods

This retrospective case–control study examines the association of reflux in two populations exposed to similar risk factors, including tobacco, to the extent that end‐organ malignant transformation has occurred. After IRB approval was obtained, a search of our hospital's cancer center's database was performed from 2000 to 2013. A retrospective chart review was then performed and the prevalence of gastroesophageal reflux disease among patients with laryngeal cancer (n = 290) was determined. It was then compared to the prevalence of gastroesophageal reflux disease among patients presenting with lung cancer (n = 2440) during the same time period. A multivariate logistic regression was performed to determine the association of reflux with laryngeal cancer.

Results

Taking into consideration tobacco use, there was a strong association between male gender and occurrence of laryngeal cancer as opposed to lung cancer (OR = 3.30; 95% CI 2.53–4.36, P < 0.001). There was a modest association between reflux and laryngeal cancer (OR = 1.65; 95% CI 1.19–2.25, P = 0.003). However, there was no association between reflux and the propensity for carcinoma in specific laryngeal subsites (P = 0.47).

Conclusions

In this study examining a heterogeneous population with end‐organ malignancy there was a modest association between reflux and laryngeal cancer. Further research is necessary to determine the biologic relevance of this finding.
A Remark on Configuration Spaces of Two Points
Authors: Raptis George , Salvatore Paolo
Published: April 2018

We prove a homotopy invariance result for a certain covering space of the space of ordered configurations of two points in M × X where M is a closed smooth manifold and X is any fixed aspherical space which is not a point.
Perceptions of Cognitive Aging Among Older Veterans
Authors: Bundy Brett C. , Daley Ryan T. , Clark Erika L. , Indorewalla Khushnoo , O’Connor Maureen K.
Published: April 2018

Abstract. Background and objectives: To understand the perceptions, knowledge, and understanding of memory, cognition, and aging among older veterans. Research design and methods: Twelve male, Caucasian, community-dwelling veterans from a suburban New England demographic area, aged 62 to 83 years, participated in qualitative interviews. The interviews were audio recorded, transcribed verbatim, and subsequently coded by three independent reviewers. The responses were calculated and analyzed for major themes. Results: Veterans equated healthy aging to be both of a physical and cognitive nature, although a significant subset viewed especially intact cognitive faculties to be a sign of successful aging despite physical limitations. Two of the most widely cited concerns about aging were loss of functional independence and the progression of cognitive decline into dementia, although most of the participants were unable to accurately describe dementia or Alzheimer’s disease. Military service was associated with both positive (e.g., social support) and negative (e.g., trauma) associations with aging. Most of the participants noted the importance of a healthy diet and exercise in aging but were unable to accurately describe a healthy diet or exercise regimen or the effect of these activities on the brain. Discussion and implications: Aging veterans represent a unique population among older adults, and more information is required to understand their specific needs. Older male veterans are less likely to engage in healthcare; for some, education alone may be enough to improve engagement, whereas for others an estimate of current cognitive function would provide the extra motivation required.
Reversing Earth’s Spin Moves Deserts, Reshapes Ocean Currents
Authors: den Hond Bas
Published: April 2018

A climate model with reversed rotation of Earth helps climatologists and oceanographers understand why our planet is the way it is and reveals how different it could have been.
Molecular basis for the folding of β-helical autotransporter passenger domains
Authors: Yuan Xiaojun , Johnson Matthew D. , Zhang Jing , Lo Alvin W. , Schembri Mark A. , Wijeyewickrema Lakshmi C. , Pike Robert N. , Huysmans Gerard H. M. , Henderson Ian R. , Leyton Denisse L.
Published: April 2018

Bacterial autotransporters comprise a C-terminal β-barrel domain, which must be correctly folded and inserted into the outer membrane to facilitate translocation of the N-terminal passenger domain to the cell exterior. Once at the surface, the passenger domains of most autotransporters are folded into an elongated β-helix. In a cellular context, key molecules catalyze the assembly of the autotransporter β-barrel domain. However, how the passenger domain folds into its functional form is poorly understood. Here we use mutational analysis on the autotransporter Pet to show that the β-hairpin structure of the fifth extracellular loop of the β-barrel domain has a crucial role for passenger domain folding into a β-helix. Bioinformatics and structural analyses, and mutagenesis of a homologous autotransporter, suggest that this function is conserved among autotransporter proteins with β-helical passenger domains. We propose that the autotransporter β-barrel domain is a folding vector that nucleates folding of the passenger domain.
Identification of rare sequence variation underlying heritable pulmonary arterial hypertension
Authors: Gräf Stefan , Haimel Matthias , Bleda Marta , Hadinnapola Charaka , Southgate Laura , Li Wei , Hodgson Joshua , Liu Bin , Salmon Richard M. , Southwood Mark , Machado Rajiv D. , Martin Jennifer M. , Treacy Carmen M. , Yates Katherine , Daugherty Louise C. , Shamardina Olga , Whitehorn Deborah , Holden Simon , Aldred Micheala , Bogaard Harm J. , Church Colin , Coghlan Gerry , Condliffe Robin , Corris Paul A. , Danesino Cesare , Eyries Mélanie , Gall Henning , Ghio Stefano , Ghofrani Hossein-Ardeschir , Gibbs J. Simon R. , Girerd Barbara , Houweling Arjan C. , Howard Luke , Humbert Marc , Kiely David G. , Kovacs Gabor , MacKenzie Ross Robert V. , Moledina Shahin , Montani David , Newnham Michael , Olschewski Andrea , Olschewski Horst , Peacock Andrew J. , Pepke-Zaba Joanna , Prokopenko Inga , Rhodes Christopher J. , Scelsi Laura , Seeger Werner , Soubrier Florent , Stein Dan F. , Suntharalingam Jay , Swietlik Emilia M. , Toshner Mark R. , van Heel David A. , Vonk Noordegraaf Anton , Waisfisz Quinten , Wharton John , Wort Stephen J. , Ouwehand Willem H. , Soranzo Nicole , Lawrie Allan , Upton Paul D. , Wilkins Martin R. , Trembath Richard C. , Morrell Nicholas W.
Published: April 2018

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-β pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH. We demonstrate familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, lead to reduced secretion from transfected cells. In addition, we identify pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings contribute new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention.
High power surface emitting terahertz laser with hybrid second- and fourth-order Bragg gratings
Authors: Jin Yuan , Gao Liang , Chen Ji , Wu Chongzhao , Reno John L. , Kumar Sushil
Published: April 2018

A surface-emitting distributed feedback (DFB) laser with second-order gratings typically excites an antisymmetric mode that has low radiative efficiency and a double-lobed far-field beam. The radiative efficiency could be increased by using curved and chirped gratings for infrared diode lasers, plasmon-assisted mode selection for mid-infrared quantum cascade lasers (QCLs), and graded photonic structures for terahertz QCLs. Here, we demonstrate a new hybrid grating scheme that uses a superposition of second and fourth-order Bragg gratings that excite a symmetric mode with much greater radiative efficiency. The scheme is implemented for terahertz QCLs with metallic waveguides. Peak power output of 170 mW with a slope-efficiency of 993 mW A−1 is detected with robust single-mode single-lobed emission for a 3.4 THz QCL operating at 62 K. The hybrid grating scheme is arguably simpler to implement than aforementioned DFB schemes and could be used to increase power output for surface-emitting DFB lasers at any wavelength.
Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs
Authors: Ikeda Takashi , Hikichi Takafusa , Miura Hisashi , Shibata Hirofumi , Mitsunaga Kanae , Yamada Yosuke , Woltjen Knut , Miyamoto Kei , Hiratani Ichiro , Yamada Yasuhiro , Hotta Akitsu , Yamamoto Takuya , Okita Keisuke , Masui Shinji
Published: April 2018

Multicellular organisms consist of multiple cell types. The identity of these cells is primarily maintained by cell-type-specific gene expression programs; however, mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease β-actin monomer quantity result in the nuclear accumulation of Mkl1 and the activation of Srf, which downregulate cell-type-specific genes and alter the epigenetics of regulatory regions and chromatin organization. Mice overexpressing Srf exhibit various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases.
Conditional privatization of a public siderophore enables Pseudomonas aeruginosa to resist cheater invasion
Authors: Jin Zhenyu , Li Jiahong , Ni Lei , Zhang Rongrong , Xia Aiguo , Jin Fan
Published: April 2018

Understanding the mechanisms that promote cooperative behaviors of bacteria in their hosts is of great significance to clinical therapies. Environmental stress is generally believed to increase competition and reduce cooperation in bacteria. Here, we show that bacterial cooperation can in fact be maintained because of environmental stress. We show that Pseudomonas aeruginosa regulates the secretion of iron-scavenging siderophores in the presence of different environmental stresses, reserving this public good for private use in protection against reactive oxygen species when under stress. We term this strategy “conditional privatization”. Using a combination of experimental evolution and theoretical modeling, we demonstrate that in the presence of environmental stress the conditional privatization strategy is resistant to invasion by non-producing cheaters. These findings show how the regulation of public goods secretion under stress affects the evolutionary stability of cooperation in a pathogenic population, which may assist in the rational development of novel therapies.
Gene expression links functional networks across cortex and striatum
Authors: Anderson Kevin M. , Krienen Fenna M. , Choi Eun Young , Reinen Jenna M. , Yeo B. T. Thomas , Holmes Avram J.
Published: April 2018

The human brain is comprised of a complex web of functional networks that link anatomically distinct regions. However, the biological mechanisms supporting network organization remain elusive, particularly across cortical and subcortical territories with vastly divergent cellular and molecular properties. Here, using human and primate brain transcriptional atlases, we demonstrate that spatial patterns of gene expression show strong correspondence with limbic and somato/motor cortico-striatal functional networks. Network-associated expression is consistent across independent human datasets and evolutionarily conserved in non-human primates. Genes preferentially expressed within the limbic network (encompassing nucleus accumbens, orbital/ventromedial prefrontal cortex, and temporal pole) relate to risk for psychiatric illness, chloride channel complexes, and markers of somatostatin neurons. Somato/motor associated genes are enriched for oligodendrocytes and markers of parvalbumin neurons. These analyses indicate that parallel cortico-striatal processing channels possess dissociable genetic signatures that recapitulate distributed functional networks, and nominate molecular mechanisms supporting cortico-striatal circuitry in health and disease.
Deterministic realization of collective measurements via photonic quantum walks
Authors: Hou Zhibo , Tang Jun-Feng , Shang Jiangwei , Zhu Huangjun , Li Jian , Yuan Yuan , Wu Kang-Da , Xiang Guo-Yong , Li Chuan-Feng , Guo Guang-Can
Published: April 2018

Collective measurements on identically prepared quantum systems can extract more information than local measurements, thereby enhancing information-processing efficiency. Although this nonclassical phenomenon has been known for two decades, it has remained a challenging task to demonstrate the advantage of collective measurements in experiments. Here, we introduce a general recipe for performing deterministic collective measurements on two identically prepared qubits based on quantum walks. Using photonic quantum walks, we realize experimentally an optimized collective measurement with fidelity 0.9946 without post selection. As an application, we achieve the highest tomographic efficiency in qubit state tomography to date. Our work offers an effective recipe for beating the precision limit of local measurements in quantum state tomography and metrology. In addition, our study opens an avenue for harvesting the power of collective measurements in quantum information-processing and for exploring the intriguing physics behind this power.
Epigenetic activation during T helper 17 cell differentiation is mediated by Tripartite motif containing 28
Authors: Jiang Yu , Liu Ying , Lu Huiping , Sun Shao-Cong , Jin Wei , Wang Xiaohu , Dong Chen
Published: April 2018

Epigenetic regulation is important for T-cell fate decision. Although STAT3 is known to initiate Th17 differentiation program, the downstream mechanism is unclear. Here we show that Tripartite motif containing 28 (Trim28) expression in Th17 cells is required for Th17-mediated cytokine production and experimental autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28-bound regions overlap with almost all Th17-specific super-enhancers (SE), and that those SEs are impaired by the deficiency of STAT3 or TRIM28, but not of RORγt. Importantly, IL-6-STAT3 signaling facilitates TRIM28 binding to theIl17-Il17flocus, and this process is required for epigenetic activation and high-order chromosomal interaction. TRIM28 also forms a complex with STAT3 and RORγt, and promotes the recruitment of RORγt to its target cytokine genes. Our study thus suggests TRIM28 to be important for the epigenetic activation during Th17 cell differentiation, and prompts the potential use of epigenetic interventions for Th17-related autoimmune diseases.
Fossil black smoker yields oxygen isotopic composition of Neoproterozoic seawater
Authors: Hodel F. , Macouin M. , Trindade R. I. F. , Triantafyllou A. , Ganne J. , Chavagnac V. , Berger J. , Rospabé M. , Destrigneville C. , Carlut J. , Ennih N. , Agrinier P.
Published: April 2018

The evolution of the seawater oxygen isotopic composition (δ18O) through geological time remains controversial. Yet, the past δ18Oseawater is key to assess past seawater temperatures, providing insights into past climate change and life evolution. Here we provide a new and unprecedentedly precise δ18O value of −1.33 ± 0.98‰ for the Neoproterozoic bottom seawater supporting a constant oxygen isotope composition through time. We demonstrate that the Aït Ahmane ultramafic unit of the ca. 760 Ma Bou Azzer ophiolite (Morocco) host a fossil black smoker-type hydrothermal system. In this system we analyzed an untapped archive for the ocean oxygen isotopic composition consisting in pure magnetite veins directly precipitated from a Neoproterozoic seawater-derived fluid. Our results suggest that, while δ18Oseawater and submarine hydrothermal processes were likely similar to present day, Neoproterozoic oceans were 15–30 °C warmer on the eve of the Sturtian glaciation and the major life diversification that followed.
Pausing controls branching between productive and non-productive pathways during initial transcription in bacteria
Authors: Dulin David , Bauer David L. V. , Malinen Anssi M. , Bakermans Jacob J. W. , Kaller Martin , Morichaud Zakia , Petushkov Ivan , Depken Martin , Brodolin Konstantin , Kulbachinskiy Andrey , Kapanidis Achillefs N.
Published: April 2018

Transcription in bacteria is controlled by multiple molecular mechanisms that precisely regulate gene expression. It has been recently shown that initial RNA synthesis by the bacterial RNA polymerase (RNAP) is interrupted by pauses; however, the pausing determinants and the relationship of pausing with productive and abortive RNA synthesis remain poorly understood. Using single-molecule FRET and biochemical analysis, here we show that the pause encountered by RNAP after the synthesis of a 6-nt RNA (ITC6) renders the promoter escape strongly dependent on the NTP concentration. Mechanistically, the paused ITC6 acts as a checkpoint that directs RNAP to one of three competing pathways: productive transcription, abortive RNA release, or a new unscrunching/scrunching pathway. The cyclic unscrunching/scrunching of the promoter generates a long-lived, RNA-bound paused state; the abortive RNA release and DNA unscrunching are thus not as tightly linked as previously thought. Finally, our new model couples the pausing with the abortive and productive outcomes of initial transcription.
HOXA9 inhibits HIF-1α-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development
Authors: Zhou Liang , Wang Yinghui , Zhou Meijuan , Zhang Ying , Wang Pengfei , Li Xiaoxing , Yang Jing , Wang Hongmei , Ding Zhenhua
Published: April 2018

Glycolytic reprogramming is a typical feature of many cancers; however, key regulators of glucose metabolism reengineering are poorly understood, especially in cutaneous squamous cell carcinoma (cSCC). Here, Homeobox A9 (HOXA9), a direct target of onco-miR-365, is identified to be significantly downregulated in cSCC tumors and cell lines. HOXA9 acts as a tumor suppressor and inhibits glycolysis in cSCC in vitro and in vivo by negatively regulating HIF-1α and its downstream glycolytic regulators, HK2, GLUT1 and PDK1. Mechanistic studies show that HOXA9-CRIP2 interaction at glycolytic gene promoters impeds HIF-1α binding, repressing gene expression in trans. Our results reveal a miR-365-HOXA9-HIF-1α regulatory axis that contributes to the enhanced glycolysis in cSCC development and may represent an intervention target for cSCC therapy.
Genome-wide excision repair in Arabidopsis is coupled to transcription and reflects circadian gene expression patterns
Authors: Oztas Onur , Selby Christopher P. , Sancar Aziz , Adebali Ogun
Published: April 2018

Plants are exposed to numerous DNA-damaging stresses including the exposure to ultraviolet (UV) component of solar radiation. They employ nucleotide excision repair to remove DNA-bulky adducts and to help eliminate UV-induced DNA lesions, so as to maintain their genome integrity and their fitness. Here, we generated genome-wide single-nucleotide resolution excision repair maps of UV-induced DNA damage in Arabidopsis at different circadian time points. Our data show that the repair of UV lesions for a large fraction of the genome is controlled by the joint actions of the circadian clock and transcription by RNA polymerase II. Our findings reveal very strong repair preference for the transcribed strands of active genes in Arabidopsis, and 10–30% of the transcription-coupled repair is circadian time-dependent. This dynamic range in nucleotide excision repair levels throughout the day enables Arabidopsis to cope with the bulky DNA lesion-inducing environmental factors including UV.
Modular assembly of proteins on nanoparticles
Authors: Ma Wenwei , Saccardo Angela , Roccatano Danilo , Aboagye-Mensah Dorothy , Alkaseem Mohammad , Jewkes Matthew , Di Nezza Francesca , Baron Mark , Soloviev Mikhail , Ferrari Enrico
Published: April 2018

Generally, the high diversity of protein properties necessitates the development of unique nanoparticle bio-conjugation methods, optimized for each different protein. Here we describe a universal bio-conjugation approach which makes use of a new recombinant fusion protein combining two distinct domains. The N-terminal part is Glutathione S-Transferase (GST) from Schistosoma japonicum, for which we identify and characterize the remarkable ability to bind gold nanoparticles (GNPs) by forming gold–sulfur bonds (Au–S). The C-terminal part of this multi-domain construct is the SpyCatcher from Streptococcus pyogenes, which provides the ability to capture recombinant proteins encoding a SpyTag. Here we show that SpyCatcher can be immobilized covalently on GNPs through GST without the loss of its full functionality. We then show that GST-SpyCatcher activated particles are able to covalently bind a SpyTag modified protein by simple mixing, through the spontaneous formation of an unusual isopeptide bond.
A geometric approach to characterize the functional identity of single cells
Authors: Mohammadi Shahin , Ravindra Vikram , Gleich David F. , Grama Ananth
Published: April 2018

Single-cell transcriptomic data has the potential to radically redefine our view of cell-type identity. Cells that were previously believed to be homogeneous are now clearly distinguishable in terms of their expression phenotype. Methods for automatically characterizing the functional identity of cells, and their associated properties, can be used to uncover processes involved in lineage differentiation as well as sub-typing cancer cells. They can also be used to suggest personalized therapies based on molecular signatures associated with pathology. We develop a new method, called ACTION, to infer the functional identity of cells from their transcriptional profile, classify them based on their dominant function, and reconstruct regulatory networks that are responsible for mediating their identity. Using ACTION, we identify novel Melanoma subtypes with differential survival rates and therapeutic responses, for which we provide biomarkers along with their underlying regulatory networks.
Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA
Authors: Zemmour Hai , Planer David , Magenheim Judith , Moss Joshua , Neiman Daniel , Gilon Dan , Korach Amit , Glaser Benjamin , Shemer Ruth , Landesberg Giora , Dor Yuval
Published: April 2018

Detection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover. Patients with acute ST-elevation myocardial infarction show a robust cardiac cfDNA signal that correlates with levels of troponin and creatine phosphokinase (CPK), including the expected elevation-decay dynamics following coronary angioplasty. Patients with sepsis have high cardiac cfDNA concentrations that strongly predict mortality, suggesting a major role of cardiomyocyte death in mortality from sepsis. A cfDNA biomarker for cardiomyocyte death may find utility in diagnosis and monitoring of cardiac pathologies and in the study of normal human cardiac physiology and development.
Variation in Wolbachia effects on Aedes mosquitoes as a determinant of invasiveness and vectorial capacity
Authors: King Jessica G. , Souto-Maior Caetano , Sartori Larissa M. , Maciel-de-Freitas Rafael , Gomes M. Gabriela M.
Published: April 2018

Wolbachia has been introduced into Aedes aegypti mosquitoes to control the spread of arboviruses, such as dengue, chikungunya and Zika. Studies showed that certain Wolbachia strains (such as wMel) reduce replication of dengue viruses in the laboratory, prompting the release of mosquitoes carrying the bacterium into the field, where vectorial capacity can be realistically assessed in relation to native non-carriers. Here we apply a new analysis to two published datasets, and show that wMel increases the mean and the variance in Ae. aegypti susceptibility to dengue infection when introgressed into Brazil and Vietnam genetic backgrounds. In the absence of other processes, higher mean susceptibility should lead to enhanced viral transmission. The increase in variance, however, widens the basis for selection imposed by unexplored natural forces, retaining the potential for reducing transmission overall.
Author Correction: Cascaded Kerr photon-blockade sources and applications in quantum key distribution
Authors: Li Ao , Zhou Yiheng , Wang Xiang-Bin
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: An extinct vertebrate preserved by its living hybridogenetic descendant
Authors: Dubey Sylvain , Dufresnes Christophe
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Non-invasive three-dimension control of light between turbid layers using a surface quasi-point light source for precorrection
Authors: Qiao Mu , Liu Honglin , Pang Guanghui , Han Shensheng
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Variable density dependence and the restructuring of coral-reef fisheries across 25 years of exploitation
Authors: Houk Peter , Cuetos-Bueno Javier , Tibbatts Brent , Gutierrez Jay
Published: April 2018

Variable density dependence within multispecies fisheries results in species restructuring as exploitation intensifies that is poorly understood. We examined unique species-based records across 25 years of exploitation to evaluate patterns, consequences, and predictions of species replacements within three coral-reef fisheries. Body-size was an expected determinant of species replacements, as larger fishes were consistently replaced by smaller, faster-growing counterparts. However, many species with similar sizes and growth rates responded differently. Naso unicornis, a primary component of coral-reef fisheries across the Pacific, was one of the most resilient species to exploitation despite having a similar maximum size and growth as many large parrotfishes that slowly disappeared from landings. Assessments conducted for all primary target species revealed clear distinctions in compensatory responses: 31% had diminishing size structures, 18% had diminishing proportional contribution, but only 5% showed both. Standard approaches to fisheries management assume constant rates of size-and-age restructuring and rely upon metrics such as fishing-versus-natural mortality. Instead, a deeper appreciation for varying recruitment rates may help to (re)define fisheries management units and reduce complexity in multispecies fisheries. We last consider our results alongside traditional knowledge and management in the Pacific that clearly appreciated species responses, but have been lost over the years.
Identification of Morus notabilis MADS-box genes and elucidation of the roles of MnMADS33 during endodormancy
Authors: Luo Yiwei , Li Hongshun , Xiang Zhonghuai , He Ningjia
Published: April 2018

The MADS-box genes encode transcriptional regulators with various functions especially during floral development. A total of 54 putative Morus notabilis MADS-box genes (MnMADSs) were identified and phylogenetically classified as either type I (17 genes) or type II (37 genes). The detected genes included three FLOWERING LOCUS C-like (MnFLC-like) genes, MnMADS33, MnMADS50, and MnMADS7. MnFLC-like proteins could directly or indirectly repress promoter activity of the mulberry FLOWERING LOCUS T-like (MnFT) gene. Transgenic Arabidopsis thaliana overexpressing MnFLC-like genes exhibited delayed flowering and down-regulated expression of FT and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1). The gene expression analyses in floral bud indicated that MnMADS33 expression increased, while MnFT expression decreased during the induction of dormancy in response to cold conditions. Dormancy release resulted in the down-regulation of MnMADS33 expression and the up-regulation of MnFT expression. Furthermore, abscisic acid promoted the transcription of MnMADS33 and MnFT, although the expression level of MnFT gradually decreased. These results are consistent with the hypothesis that MnMADS33 negatively regulated the expression of MnFT to repress dormancy release and flowering in mulberry. This study may be relevant for future investigations regarding the effects of MnMADS genes on mulberry flowering development.
Author Correction: A novel quantitative PCR mediated by high-fidelity DNA polymerase
Authors: Zhang Mengling , Liu Kyle , Hu Yihong , Lin Yi , Li Yang , Zhong Ping , Jin Xia , Zhu Xiaoli , Zhang Chiyu
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
A Highly Efficient Adsorbent Cu-Perusian Blue@Nanodiamond for Cesium in Diluted Artificial Seawater and Soil-Treated Wastewater
Authors: Matsumoto Kazuko , Yamato Hideyuki , Kakimoto Seishiro , Yamashita Takeshi , Wada Ryutaro , Tanaka Yoshiaki , Akita Masakazu , Fujimura Tadamasa
Published: April 2018

A new adsorbent Cu-Perussian blue@Nanodiamond (Cu-PB@DND) for Cs+ removal was prepared and characterized with IR, SEM, X-ray diffraction, particle size analysis, and zeta-potential. The adsorbent consists of a core of aggregated detonation nanodiamond (DND) particles with the surface treated with Cu-PB. Cesium adsorption was studied in two modes; a co-precipitation mode and a batch mode. In the co-precipitation mode, DND, CuCl2, and K4[Fe(CN)6] were added sequentially to a Cs+ solution in diluted artificial seawater. In the batch mode, adsorbent Cu-PB@DND was dispersed into a Cs+ solution with stirring. The distribution coefficient (Kd) of the co-precipitation mode was 8.8 × 107 (mL/g) at Cs+ 6.6 ppm in 0.07% seawater. The Kd value of the batch mode was 1.3 × 106 (mL/g). Precipitation of Cs+-incorporated particles was complete, and post filtration was not necessary. Excess copper and iron ions were completely removed and were not detected in the supernatant. The adsorption data for Cu-PB@DND were analyzed by assuming Langmuir isotherm and a good fit was obtained with a maximum adsorption capacity Qmax of 759 mg/g. The co-precipitation method was also applied to soil-treated wastewater.
Novel Indole-fused benzo-oxazepines (IFBOs) inhibit invasion of hepatocellular carcinoma by targeting IL-6 mediated JAK2/STAT3 oncogenic signals
Authors: Singh Ashok K. , Bhadauria Archana S. , Kumar Umesh , Raj Vinit , Rai Amit , Kumar Pranesh , Keshari Amit K. , Kumar Dinesh , Maity Biswanath , Nath Sneha , Prakash Anand , Saha Sudipta
Published: April 2018

Inspired by the well-documented tumor protecting ability of paullones, recently, we synthesized novel paullone-like scaffolds, indole-fused benzo-oxazepines (IFBOs), and screened them against hepatocellular carcinoma (HCC) specific Hep-G2 cells. Three of the synthesized compounds significantly attenuated the progression of HCCin vitro. By computational studies, we further discovered that IFBOs exhibited a stable binding complex with the IL-6 receptor. In this context, we investigatedin vivostudy using the nitrosodiethyl amine (NDEA)-induced HCC model, which strengthened our previous findings by showing the blockade of the IL-6 mediated JAK2/STAT3 oncogenic signaling pathway. Treatment with IFBOs showed remarkable attenuation of cellular proliferation, as evidenced through a decrease in the number of nodules, restoration of body weight, oxidative stress parameters, liver marker enzymes and histological architecture. Interestingly, using a metabolomic approach we further discovered that IFBOs can restore the perturbed metabolic profile associated with the HCC condition to normalcy. Particularly, the efficacy of compound6afor an anti-HCC response was significantly better than the marketed chemotherapeutic drug, 5-fluorouracil. Altogether, these remarkable findings open up possibilities of developing IFBOs as novel future candidate molecules for plausible alternatives for HCC treatment.
Efficient white phosphorescent organic light-emitting diodes using ultrathin emissive layers (<1 nm)
Authors: Yu Haojian , Dai Xudong , Yao Fangnan , Wei Xiang , Cao Jin , Jhun Chulgyu
Published: April 2018

In this paper, efficient phosphorescent white organic light-emitting diodes (WOLEDs) were fabricated based on ultrathin doping-free emissive layers and mixed bipolar interlayers. The energy transfer processes were proved via the research of WOLEDs with different interlayer thicknesses and transient photoluminescence lifetime. WOLEDs with optimized thickness of doping-free emissive layers show maximum current efficiency of 47.8 cd/A and 44.9 cd/A for three-colors and four-colors WOLEDs, respectively. The Commission Internationale de L’Eclairage coordinates shows a very slight variation of ( ± 0.02, ± 0.02) from 5793 cd/m2to 11370 cd/m2for three-colors WOLEDs and from 3038 cd/m2to 13720 cd/m2for four-colors WOLEDs, respectively. The stability of the spectra is attributed to the stable and sequential energy transfer among the various dyes. The color temperature of four-colors WOLEDs can be obtained from 2659 to 6636 by adjusting the thickness of ultrathin emissive layer.
Spatial fishing restrictions benefit demersal stocks in the northeastern Mediterranean Sea
Authors: Dimarchopoulou Donna , Dogrammatzi Aikaterini , Karachle Paraskevi K. , Tsikliras Athanassios C.
Published: April 2018

The multi-level benefits that marine organisms gain when protected from fishing are well acknowledged. Here, we investigated the effects of a 40-year trawling ban on the status of targeted and non-targeted marine species within a major fishing ground in the northeastern Mediterranean Sea (Thermaikos Gulf, Aegean Sea). Biomass and somatic length of fish and invertebrates (six commercial and three non-commercial demersal species) were measured in three areas of varying fishing pressure, depending on the temporal and spatial operational regimes of fishing vessels. The positive effects of fishing restrictions on the studied demersal stocks were clearly revealed, as the commercial fish species exhibited higher biomass in the intermediate and low pressure areas, as well as increasing maximum and mean total length (and other length indicators) with decreasing fishing effort. The mean total length of non-commercial species generally did not differ among areas, except for species caught and discarded at high rates. The present study shows that fishing does alter the population structure and biomass of commercial demersal species, and that fishing restrictions greatly contribute to improving the status of demersal populations within the restricted areas by providing a refuge for large individuals and their important contribution to the gene pool.