bluuebunny/crossref_metadata_2025 huggingface dataset:
On methods of coverage of sociopolitical aspects of urban development by social disciplines
Authors: Andreev Igor
Published: August 2018

The author has identified a trend towards the politicization of urban planning in Russia, caused by a set of factors. The author believes that students should be timely taught to adequately respond to the attempts of the leading political parties and movements to influence the urban planning industry. These attempts represent the imposition of particular urban plans for their benefit, the resolution of urban planning conflicts in the best interests of particular parties, etc. According to the author, who has accumulated an extensive lecturing experience, this goal is attainable by offering social disciplines, including Sociology, Sociology of Urban Development, Bases of Social Regulation and Public Relations, to bachelor students, majoring in urban planning at the Moscow State University of Civil Engineering. The author has considered several issues of teaching methods, in particular, he has identified the list of political problems to be analyzed and the type of classes to be organized, etc. In the report, the author makes a conclusion that the focus on the sociopolitical aspects of urban planning in the courses of social disciplines improves the students’ understanding of the nature of urban planning as a democratic practice.
Application of failure mode and effects analysis in ecology in Russia
Authors: Borkovskaya Victoria , Passmore David
Published: August 2018

The article presents a comprehensive review of the FMEA analysis (the failure modes and effects analysis) in the construction industry in the Russian Federation and suggests the same analysis, which can be applied to ecological issues. The paper analyzes the existing legislative and normative acts in this area, modern approaches to the introduction and regulation of the definition of defects in production and construction. Particular attention is paid to the consideration of Failure Mode and Effects Analysis - this is a formalized procedure for analyzing and finalizing the projected technical facility, the manufacturing process, the operation and storage rules, the maintenance and repair systems of technical facilities, based on the identification of possible (observed) defects with their consequences and cause-effect relationships in their occurrence, and an assessment of the criticality of these defects.
Integrated construction supervision as a tool to reduce the developer’s risks when implementing new and redevelopment projects
Authors: Topchiy Dmitriy , Shatrova Anastasia , Yurgaytis Alexey
Published: August 2018

The article describes the importance of construction supervision by a Developer (EPCM Contractor) as an effective tool for reducing potential risks when implementing investment and construction projects. In general, the paper describes the practice of hiring construction supervisors, the need for an integrated, systemic approach to the work acceptance process. The proposed integrated verification supervision method includes Contractor’s laboratory data confirmation in order to optimize and improve the control functions. The method was analyzed using existing statistical techniques. The paper suggests ways for determining quality and quantity characteristics of sampling (verification supervision) from the general totality (Contractor’s initial supervision) while observing the representativeness condition.
Analysis of factors affecting Ho Chi Minh city’s office rental price using Hedonic model
Authors: Le Van Thuong , Nguyen Quynh Hoa , Nguyen Van Toan
Published: August 2018

Research on the application of Hedonic model in analyzing factors which affect office rental price in HCM city CBD area. The author uses primary data source comprised of 146 observations collected in district 1 and district 3 during the first 6 months of 2015. By using OLS method, together with three regression models commonly used in researches on the application of Hedonic model, the result shows significant impact of factors, such as building classification, management fee, road on which the building is situated, and district location on office rental price. The result of this research can be applied in the field of real estate management, investment consulting, office rental.
Energy consumption reduction at all stages of residential buildings life cycle by means of queuing systems
Authors: Mishchenko Valeriy , Kolodyazhniy Sergei , Gorbaneva Elena
Published: August 2018

Buildings are the largest source of carbon emissions and energy consumption around the world. Currently, the construction sector focuses on energy efficient and carbon emission reduction technologies to reduce the effect of a green house and improve the environment. The energy aspects of buildings depend on the early design process. The energy consumed by the building can be reduced to 80% by optimizing the orientation, the shape of the building, the insulation and ventilation during the design and management of the facilities after the completion of the construction. The reductions of energy consumption are fundamental to the International Energy Agency (IEA) goal, which is to reduce global carbon emissions by 77% against the projected data for 2050 to achieve the stabilized CO2 level provided by the Intergovernmental Panel on Climate Change (IPCC). In this issue, research and development of energy-efficient technologies are important, which play a crucial role in reducing initial costs and increasing energy conservation. To do this, it is recommended to use simulation modeling of the queue management system, which has practical application for both large systems and for private systems.
Trends and improving methods of assessing costs of land plots seized by the state
Authors: Tabak Larisa , Suvorova Natasha
Published: August 2018

The study is analyzing the current Russian legal systems and practices of the evaluating process of seizing land for state and municipal needs. As a result, a number of conflicts of legislative norms were revealed. Most of them are caused by different interpretation of the terms of valuation the seized property and the type of recoverable value by legal acts. The main direction of improving this mechanism is the formation of an executive department to coordinate activities and eliminate conflicts.
Problems of Application of the Environmental Legislation to the Maintenance and Construction of Urban Buildings and Structures: the Russian Experience
Authors: Igor’ Petrovich Pryadko , Igor’ Michajlovich Lebedev
Published: August 2018

In the paper, the co-authors analyze the legal methods applied to create the biosphere compatible urban environment. The co-authors analyze a legal case on the calculation of maximal acceptable emmissions in the environmental section of a design project. The co-authors assess the legal consequences of termination of agreements through legal proceedings. The co-authors address the cases of practical application of the Russian regulatory acts. The co-authors also analyze the binding requirements applied to the environmental protection documentation.
Audit of economic security as an effective tool to prevent corruption in a construction company
Authors: Domracheva Larisa , Karanina Elena , Bakhtimov Alexander , Kochetkov Maxim
Published: August 2018

An audit of economic security helps to prevent corruption, as well as an assessment of awareness in the struggle against corruption. Audit can promote the implementation of ways to protect the economy of the construction industry against corruption. The authors pay special attention to the problem of the construction industry in Russia. Practical questions of the audit of economic security, which are considered in the article, solve the problems of financial control in the system of anti-corruption policy. The purpose of this study is to develop an audit mechanism for economic security, as a system to prevent internal and external threats and risks. The main concept of the research is aimed at the formation of an audit of economic security in the construction industry. Effective work to prevent corruption in the relations of construction organizations is ensured by the formation of an internal control system to prevent the causes of corruption in the construction sector. It is necessary to take into account the fact that analysis of risk factors at the level of the operating segment in the construction industry can contribute to the development of this area.
Beiträge zur Vermeidung von Zwang in der Akutpsychiatrie
Authors: Wullschleger Alexandre , Mielau Juliane , Mahler Lieselotte , Vandamme Angelika , Montag Christiane
Published: August 2018

Die berechtigte Forderung nach Vermeidung von Zwang in der der psychiatrischen Behandlung erfordert ein geglücktes Zusammenspiel von Veränderungen struktureller Voraussetzungen und therapeutischer Prozesse, aber auch individueller Haltungen und Fertigkeiten. Der Artikel beschreibt aktuelle therapeutische Ansätze und Möglichkeiten, die Anwendung von Zwangsmaßnahmen zu reduzieren und eine gewaltfreie, partizipative Behandlung psychisch erkrankter Menschen sicherzustellen. Diese werden vor dem Hintergrund rechtlicher und sozialer Aspekte, struktureller Besonderheiten und Personalausstattung, wie auch des subjektiven Erlebens und des Rechts der Betroffenen auf Behandlung und Schutz im Falle einer die freie Selbstbestimmung einschränkenden Erkrankung diskutiert.
Einhaltung der Menschenrechte in der Psychiatrie
Authors: Osterfeld Margarete , Lababidi Hadil , Langfeldt Marina
Published: August 2018

Der Artikel gibt einen Überblick über die Entstehung und die praktische Arbeit der von den Vereinten Nationen initiierten nationalen und internationalen Kontrollmechanismen zur Einhaltung der Menschenrechte in der Psychiatrie in Deutschland und weltweit. Einleitend werden die dafür erforderlichen rechtlichen und psychiatriepolitischen Entwicklungen geschildert, ausgehend von Pinel vor 200 Jahren über die Allgemeinen Erklärung der Menschenrechte von 1948 bis hin zu der Antifolterkonvention der Vereinten Nationen (CAT). Sodann wird die in Deutschland eingerichtete Nationale Stelle zur Verhütung von Folter und Misshandlung vorgestellt, die seit ihrem Bestehen fast vierzig Heimeinrichtungen und psychiatrische Kliniken besucht und der Öffentlichkeit darüber berichtet hat. Im Anschluss daran folgt ein Überblick über Besuche des Unterausschusses der Antifolterkonvention, des SPT, in einzelnen Staaten, an denen die Erstautorin teilgenommen hat. Da die Diktion der meisten nationalen und internationalen Berichte unausgesprochen von westlichem Gedankengut geprägt ist, folgt abschließend ein Exkurs über Demenz im islamischen Kulturraum. Ziel des Artikels ist es, einen Anreiz zur Diskussion bioethischer Fragestellungen unter Berücksichtigung mehrerer Perspektiven zu geben. Die Bedeutung zivilgesellschaftlicher Organisationen für die zukünftige Entwicklung eines interdisziplinären und interkulturellen Austausches wird dabei herausgearbeitet.
Encephalocraniocutaneous Lipomatosis (Haberland Syndrome or Fishman Syndrome)
Authors: Garozzo Maria , Attardo Daniele , Smilari Pierluigi , Greco Filippo , Fiumara Agata , Polizzi Agata , Pirrone Concetta , Zanghì Antonio , Schepis Carmelo , Lacarrubba Francesco , Micali Giuseppe , Ruggieri Martino , Praticò Andrea , Mazzurco Marina
Published: August 2018

Encephalocraniocutaneous lipomatosis is a sporadic, congenital neurocutaneous disorder characterized by the involvement of skin, central nervous system, and eye. A non-hereditary, autosomal mutation that may survive only in a mosaic state may be the cause of the clinical picture of the syndrome. Less than 80 patients have been so far reported and their clinical manifestations consisted of unilateral lipomatous hamartoma of the scalp or eyelid, epibulbar choristomas, and ipsilateral brain malformations. There is no clinical correlation between the severity of brain malformations and the clinical manifestations, and many patients with extremely extensive cerebral abnormalities are only minimal symptomatic. Seizures and mental retardation may also occur. The natural history is often favorable, without drug-resistant seizures and normal intelligence in most of the cases.
The Future of the Lecture in Neurology Education
Authors: Schaefer Sara , Dominguez Moises , Moeller Jeremy
Published: August 2018

The lecture has been a core pedagogical method since the early days of formal medical education. Although approaches to formal lectures have evolved over the years, there has been ongoing debate about the role that lectures should play in modern medical education. Arguably, traditional lectures do not align well with modern learning theory, and do not take full advantage of our current knowledge of how people learn. In many modern medical curricula, lectures have been replaced by self-study activities, including video-based lectures, computer-based learning modules, and other self-directed learning. We argue that scheduled “together time” is still important, particularly in neurology education, where there is a strong emphasis on clinical reasoning. We outline alternative teaching methods that effectively use this time, including the flipped classroom, just-in-time teaching, problem-based learning, and team-based learning. We discuss ways in which these approaches may be particularly conducive to components of neurology education.
Complications of Nasoseptal Flap Reconstruction: A Systematic Review
Authors: Lavigne Philippe , Faden Daniel , Wang Eric , Snyderman Carl
Published: August 2018

Objective The nasoseptal flap (NSF) is considered the primary vascularized flap for reconstruction of dural defects with endoscopic endonasal surgery (EES) of the skull base. However, the complications and morbidities associated with this reconstructive flap are poorly understood. This article presents a systematic review of the complications and morbidities related to the use of the NSF in skull base surgery.

Method A systematic review of the literature based on published guidelines was performed to identify potential complications and morbidities related to the NSF. The MEDLINE and Embase databases were searched from January 1, 1950 to February 5, 2018.

Results Twenty-seven articles were identified. Reported complications were as follows: NSF necrosis (4 studies; [0–1.3%]), mucocele formation (5 studies; [0–3.6%]), septal perforation (6 studies, [0–14.4%]), nasal dorsum collapse (2 studies, [0.7–5.8%]), effects on quality of life (QoL) (8 studies), and olfactory loss (11 studies).

Conclusion Although complications associated with the NSF may be underreported in the literature, the NSF appears to be a safe and reliable reconstructive flap in EES of the skull base.
Ion cyclotron resonant heating in the central cell of the Keda Mirror with AXisymmetricity (KMAX)
Authors: Liu Ming , Yi Hongshen , Zhu Guanghui , Yang Zhida , Lin Munan , Sun Xuan
Published: August 2018

In this paper, we report the results of ion cyclotron resonance frequency (ICRF) heating in the central cell of a fully axisymmetric tandem mirror. With a total power of 100 kW radiated by double half-turn and half-turn antennas, the plasma diamagnetism increases by 15-fold, with a corresponding peak β⊥ ∼2%, density ∼1.5×1018m−3, and total temperature ∼60 eV. The effects of the magnetic configuration on resonance heating and wave emission are studied by varying the magnetic fields at the midplane and at the location of the antennas, respectively; the results confirm that the magnetic beach configuration is key to successful ICRF heating. The axial phase speed measurements suggest that the excited wave is a slow wave in the plasma core and a fast wave at the edge.
Molecular beam epitaxy growth and optical properties of Mg3N2 films
Authors: Wu Peng , Tiedje Thomas
Published: August 2018

Epitaxial Mg3N2 films with a (100) orientation have been grown by plasma-assisted molecular beam epitaxy on single crystal MgO substrates. The growth was monitored in situ by both reflection high-energy electron diffraction and optical reflectivity. The growth rate was determined from the optical reflectivity during growth. The index of refraction of Mg3N2 was measured by spectroscopic ellipsometry and found to be in good agreement with the in situ reflectivity. The optical bandgap was found to be ∼2.5 eV from transmission measurements.
Development of a scanning electron microscopy with polarization analysis system for magnetic imaging with ns time resolution and phase-sensitive detection
Authors: Schönke Daniel , Oelsner Andreas , Krautscheid Pascal , Reeve Robert M. , Kläui Mathias
Published: August 2018

Scanning electron microscopy with polarization analysis is a powerful lab-based magnetic imaging technique offering simultaneous imaging of multiple magnetization components and a very high spatial resolution. However, one drawback of the technique is the long required acquisition time resulting from the low inherent efficiency of spin detection, which has limited the applicability of the technique to certain quasi-static measurement schemes and materials with high magnetic contrast. Here we demonstrate the ability to improve the signal-to-noise ratio for particular classes of measurements involving periodic excitation of the magnetic structure via the implementation of a digital phase-sensitive detection scheme facilitated by the integration of a time-to-digital converter to the system. The modified setup provides dynamic imaging capabilities using selected time windows and finally full time-resolved imaging with a demonstrated time resolution of better than 2 ns.
Time-resolved nuclear dynamics in bound and dissociating acetylene
Authors: Burger C. , Atia-Tul-Noor A. , Schnappinger T. , Xu H. , Rosenberger P. , Haram N. , Beaulieu S. , Légaré F. , Alnaser A. S. , Moshammer R. , Sang R. T. , Bergues B. , Schuurman M. S. , de Vivie-Riedle R. , Litvinyuk I. V. , Kling M. F.
Published: August 2018

We have investigated nuclear dynamics in bound and dissociating acetylene molecular ions in a time-resolved reaction microscopy experiment with a pair of few-cycle pulses. Vibrating bound acetylene cations or dissociating dications are produced by the first pulse. The second pulse probes the nuclear dynamics by ionization to higher charge states and Coulomb explosion of the molecule. For the bound cations, we observed vibrations in acetylene (HCCH) and its isomer vinylidene (CCHH) along the CC-bond with a periodicity of around 26 fs. For dissociating dication molecules, a clear indication of enhanced ionization is found to occur along the CH- and CC-bonds after 10 fs to 40 fs. The time-dependent ionization processes are simulated using semi-classical on-the-fly dynamics revealing the underling mechanisms.
Fast water flow through graphene nanocapillaries: A continuum model approach involving the microscopic structure of confined water
Authors: Neek-Amal M. , Lohrasebi A. , Mousaei M. , Shayeganfar F. , Radha B. , Peeters F. M.
Published: August 2018

Water inside a nanocapillary becomes ordered, resulting in unconventional behavior. A profound enhancement of water flow inside nanometer thin capillaries made of graphene has been observed [Radha et al., Nature (London) 538, 222 (2016)]. Here, we explain this enhancement as due to the large density and the extraordinary viscosity of water inside the graphene nanocapillaries. Using the Hagen-Poiseuille theory with slippage-boundary condition and incorporating disjoining pressure term in combination with results from molecular dynamics simulations, we present an analytical theory that elucidates the origin of the enhancement of water flow inside hydrophobic nanocapillaries. Our work reveals a distinctive dependence of water flow in a nanocapillary on the structural properties of nanoconfined water in agreement with experiment, which opens a new avenue in nanofluidics.
UV light activated NO2 gas sensing based on Au nanoparticles decorated few-layer MoS2 thin film at room temperature
Authors: Zhou Yong , Zou Cheng , Lin Xiaogang , Guo Yongcai
Published: August 2018

Nitrogen dioxide (NO2) plays a key role in environmental protection and human health. Recently, molybdenum disulfide (MoS2) representative of novel 2D materials has been utilized to detect NO2 gas, still hindered by the weak response, high operation temperature, as well as poor recovery characteristics. Herein, we report a UV light-assisted, room-temperature, recoverable, sensitive and selective NO2 gas sensing based on few-layer MoS2 nanosheet-Au nanoparticle composites serving as the sensing layer. In the dark condition, the as-prepared MoS2-Au sensor showed a response of 10% toward 2.5 ppm NO2 more than two times larger than MoS2 one, arising from more reaction sites (spillover effect and produced interfaces) and smaller baseline resistance after Au incorporation. Undesirably, all sensors exhibited an incomplete recovery. When MoS2-Au sensors were exposed to NO2 gas under UV illumination, better performance in terms of three-time enhanced response, full recovery and favorable repeatability was achieved in comparison with that in the dark case. Two aspects were responsible for these phenomena. On one hand, additional photoinduced charge carriers ensured sufficient gas-solid interactions between sensing layer and target molecules, thereby resulting in a larger response. The other aspect lay in effective separation of these charge carriers at MoS2/Au interfaces, contributing to recoverable and repeatable reactions. MoS2-Au composites were adopted for NO2 detection under UV illumination and exhibited a promising capacity of UV photodetector as well as an inspiring room-temperature gas detection, which provided an alternative strategy to design a single optoelectronic device with multi-functions.
“Do-it-in-classroom” fabrication of microfluidic systems by replica moulding of pasta structures
Authors: Nguyen Ngan , Thurgood Peter , Zhu Jiu Yang , Pirogova Elena , Baratchi Sara , Khoshmanesh Khashayar
Published: August 2018

Here, we describe a novel method for fabrication of microfluidic structures in classroom environments. This method is based on replica moulding of pasta structures in polydimethylsiloxane. Placing pasta structures on a petroleum jelly base layer enables templating round-shaped structures with controllable cross-sectional profiles. The pasta structures can be easily deformed and combined to create more complex 3D microfluidic structures. Proof-of-concept experiments indicate the capability of this method for studying the mixing of neighbouring flows, generation of droplets, lateral migration of particles, as well as culturing, shear stress stimulation, and imaging of cells. Our “do-it-in-classroom” method bridges the gap between the classroom and the laboratory.
Bounce resonance scattering of ring current electrons by H+ band EMIC waves
Authors: Wang Qi , Fu Song , Ni Binbin , Cao Xing , Gu Xudong , Huang He
Published: August 2018

We present a detailed investigation of bounce-resonant pitch angle scattering of ring current electrons caused by electromagnetic ion cyclotron (EMIC) waves. It is found that H+ band EMIC waves can resonate with near-equatorially mirroring electrons over a wide range of L shells (i.e., 3≤L≤6) and energies and lead to the efficient transport of ring current electrons (i.e., ∼10 keV to 100 keV) from near 90° pitch angles to lower pitch angles. Computations of the bounce-resonant pitch angle scattering rates show a strong dependence on the L shell, electron energy, and resonance harmonics. When the L-shell increases, the orders of bounce resonance contributing to the whole scattering coefficient decrease, and meanwhile, it becomes difficult for the bounce resonance of higher orders to occur. Furthermore, when the electron energy increases, the bounce resonance orders decrease. Our results demonstrate that bounce-resonant scattering by H+ band EMIC waves can be an important loss mechanism for ∼10–100 keV electrons because of the absence of cyclotron resonance for ring current electrons interacting with EMIC waves. We conclude that bounce resonant scattering by H+ band EMIC waves should be incorporated into future modeling efforts of the ring current electron dynamics.
Magnetotransport properties of γ-FeMn thin films grown by high-temperature sputtering
Authors: Shiomi Yuki
Published: August 2018

γ-FeMn is a topological antiferromagnet which hosts a noncoplanar spin structure at room temperature, promising for application to antiferromagnetic spintronics. In this work, we have investigated magnetotransport properties of FeMn thin films grown by dc magnetron sputtering on Al2O3 (0001) substrates. γ-phase (fcc) FeMn thin films are successfully obtained with use of a Cu seed layer covering with the Al2O3 surface, while nonmagnetic α-phase (bcc) FeMn thin films are formed without a Cu seed layer. When the sputtering temperature is set at 500 °C, γ-FeMn films grown on Cu/Al2O3 are highly oriented along the (111) plane, but minor α-Fe phases are included owing to alloying with the Cu layer. Ferromagnetic transports of α-Fe phases are observed in Hall and Nernst effects at low magnetic fields. By contrast, the slope of Hall conductivity at high magnetic fields is found to be several times larger for the γ-FeMn phase than for the α-FeMn phase, which suggests that the antiferromagnetic spin structure of γ-FeMn contributes to the Hall effect.
The importance of selection and reporting of the sex of experimental animals
Authors: Rowe Anthony
Published: August 2018

Biased use of males and females in animal studies or omitting specific details of the sex of animals used in publications limits reproducibility, hampers the pace and likelihood of new discoveries and invites adverse events in ensuing clinical research. Hence unbiased use of males and females in animal studies and specific reporting of animal details are increasingly required by funding bodies and scientific journals worldwide. An analysis to determine how males and females are used in animal studies involving the Commonwealth Scientific and Industrial Research Organisation (CSIRO) was undertaken as part of a process to review and further support best practice. In the study 178 publications that contain animal studies and include CSIRO researchers published between January 2014 and December 2016 were analysed for the sex of animals used. The overall sex distribution was males only 26.4% (47/178), females only 15.7% (28/178), males and females 18.0% (32/178) and sex of animals unspecified 39.9% (71/178). Reasons for this distribution include species biology, farming practices and commercial relevance. Although including sex as an experimental variable provides the most information, using both sexes in an animal study requires careful consideration and planning. Furthermore, there are valid biological and experimental reasons why sex distribution in a study may not be balanced. Biological reasons include cases where the severity of disease in a given model differs between males and females, superior husbandry or production traits in one sex and hermaphroditic species that change sex with age. Examples where experiments can only be undertaken in one sex of animal include animal models of female breast cancer, female reproductive traits, male fertility studies and post-castration welfare outcomes. Where there is no biological or experimental reason for using a single sex of animal, future studies should obtain an estimate of sex effect either from the literature or with a pilot study, and experiments should be planned and reported accordingly.
Metastatic cells are preferentially vulnerable to lysosomal inhibition
Authors: Morgan Michael J. , Fitzwalter Brent E. , Owens Charles R. , Powers Rani K. , Sottnik Joseph L. , Gamez Graciela , Costello James C. , Theodorescu Dan , Thorburn Andrew
Published: August 2018

Significance

We show that there is a functional reciprocal relationship between lysosome activity and metastasis that allows chloroquine (CQ) and other inhibitors of lysosome function, such as bafilomycin A
1
, to preferentially kill human metastatic bladder cancer cells by targeting autophagy-independent lysosome functions. In addition, CQ treatment of bladder cancer cells and subsequent acquisition of resistance to this therapy lead to altered gene expression programs that drive a less aggressive and metastatic phenotype via up-regulation of ID4 (inhibitor of DNA binding 4). Clinically, this work provides a conceptual foundation for using ID4 expression as a predictive and prognostic biomarker of CQ sensitivity and metastasis in patients with bladder cancer.
Identification of a multipotent Twist2-expressing cell population in the adult heart
Authors: Min Yi-Li , Jaichander Priscilla , Sanchez-Ortiz Efrain , Bezprozvannaya Svetlana , Malladi Venkat S. , Cui Miao , Wang Zhaoning , Bassel-Duby Rhonda , Olson Eric N. , Liu Ning
Published: August 2018

Significance

Adult mammalian hearts have limited self-renewal capacity. Although mounting evidence indicates that new cardiomyocytes are derived from dedifferentiation and proliferation of existing cardiomyocytes, the contribution of adult cardiac progenitors to cardiomyocyte renewal during homeostasis and upon injury remains under debate. The basic helix–loop–helix transcription factor Twist2 is expressed in interstitial cells in the adult myocardium. Using genetic lineage tracing, we identified a Twist2-expressing cell population that gives rise to a small number of adult cardiomyocytes in vivo. These Twist2-expressing cells can differentiate into cardiomyocytes, endothelial cells, and fibroblasts in culture and contribute to cardiac renewal through cell fusion and de novo differentiation. Our findings add Twist2-expressing cells to the cellular constituents involved in adult cardiac maintenance and remodeling.
Auto-fatty acylation of transcription factor RFX3 regulates ciliogenesis
Authors: Chen Baoen , Niu Jixiao , Kreuzer Johannes , Zheng Baohui , Jarugumilli Gopala K. , Haas Wilhelm , Wu Xu
Published: August 2018

Significance

Regulatory Factor X 3 (RFX3) is one of the key transcription factors involved in cilia formation and functions. Our study reveals that auto-fatty acylation is a critical regulatory mechanism for RFX3 transcriptional activities. Fatty acylation of RFX3 is required for its dimerization, leading to transcription of cilia-associated genes. More importantly, fatty acylation of RFX3 regulates ciliogenesis and Hedgehog signaling pathways, which are associated with developmental and degenerative disorders known as ciliopathies. Our results indicate a major role of auto-fatty acylation in the regulation of RFX3 function and ciliogenesis, providing a potential link between deregulation of fatty acid metabolism to ciliopathies and diabetes.
Transfer RNA genes experience exceptionally elevated mutation rates
Authors: Thornlow Bryan P. , Hough Josh , Roger Jacquelyn M. , Gong Henry , Lowe Todd M. , Corbett-Detig Russell B.
Published: August 2018

Significance

While transcription-associated mutagenesis (TAM) has been demonstrated for protein-coding genes, its implications in shaping genome structure at transfer RNA (tRNA) loci in metazoans have not been fully appreciated. We show that cytosolic tRNAs are a striking example of TAM because of their variable rates of transcription, well-defined boundaries, and internal promoter sequences. tRNA loci have a mutation rate approximately 7- to 10-fold greater than the genome-wide average, and these mutations are consistent with signatures of TAM. These observations indicate that tRNA loci are disproportionately large contributors to mutational load in the human genome. Furthermore, the correlations between tRNA locus variation and transcription indicate that prediction of tRNA gene expression based on sequence variation data is possible.
SNARE zippering requires activation by SNARE-like peptides in Sec1/Munc18 proteins
Authors: Yu Haijia , Shen Chong , Liu Yinghui , Menasche Bridget L. , Ouyang Yan , Stowell Michael H. B. , Shen Jingshi
Published: August 2018

Significance

Soluble
N
-ethylmaleimide-sensitive factor attachment protein receptor(SNARE) proteins drive membrane fusion by zippering into coiled-coil bundles between membrane bilayers. In this work, we showed that certain layers in the SNARE bundle are dispensable for SNARE-mediated membrane fusion. However, these layers are required for fusion reactions activated by the cognate Sec1/Munc18 (SM) protein or a synthetic Vc peptide derived from the vesicular SNARE. Strikingly, we identified a conserved SNARE-like peptide (SLP) in SM proteins that structurally and functionally resembles Vc peptide. Like Vc peptide, SLP binds and activates target SNAREs, stimulating the fusion reaction. These data suggest that the SM protein uses its SNARE-like sequence to promote the SNARE zippering pathway, ensuring the efficiency of vesicle fusion.
Two novel protein
O
-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling
Authors: Takeuchi Hideyuki , Schneider Michael , Williamson Daniel B. , Ito Atsuko , Takeuchi Megumi , Handford Penny A. , Haltiwanger Robert S.
Published: August 2018

Significance

The Notch-signaling pathway is normally activated by receptor–ligand interactions. Extracellular domains (ECDs) of Notch receptors are heavily modified with
O
-linked glycans, such as
O
-glucose (
O
-Glc),
O
-fucose (
O
-Fuc), and
O
-GlcNAc. The significance of multiple types of
O
-glycans on Notch is not understood. NOTCH1 ECD interacts with ligands at multiple points, including an
O
-Glc monosaccharide on the 11th Epidermal Growth Factor (EGF) repeat (EGF11). Here, we identify two novel protein
O
-glucosyltransferases that modify NOTCH1 EGF11 with
O
-Glc. Combined deletion of the
O
-Glc site on EGF11 with
O
-Fuc modification sites on EGF8 or EGF12 markedly reduced NOTCH1 cell-surface expression or activation of NOTCH1 by Delta-like ligand 1, respectively. This study identifies a cooperative mechanism for fine-tuning the Notch-signaling pathway by different types of
O
-glycans.
Bistable emergence of oscillations in growing
Bacillus subtilis
biofilms
Authors: Martinez-Corral Rosa , Liu Jintao , Süel Gürol M. , Garcia-Ojalvo Jordi
Published: August 2018

Significance

Cell communities can become resilient to stress by undergoing collective growth oscillations, which provide periodic stress relief and are collective in the sense that they arise only for large enough numbers of cells. Collective oscillatory phenomena usually emerge continuously as the system size increases, with oscillations starting with small amplitude and slowly growing as the cells proliferate. This behavior, however, is not appropriate in situations in which the population needs to implement a full-sized response quickly. Our combined theoretical and experimental study shows that collective oscillations in bacterial biofilm communities emerge via a discontinuous transition as their size increases. This behavior may provide an evolutionary advantage to cell communities, by allowing them to quickly alter qualitatively their dynamics in response to variations in external conditions such as stress.
Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector
Authors: Cideciyan Artur V. , Sudharsan Raghavi , Dufour Valérie L. , Massengill Michael T. , Iwabe Simone , Swider Malgorzata , Lisi Brianna , Sumaroka Alexander , Marinho Luis Felipe , Appelbaum Tatyana , Rossmiller Brian , Hauswirth William W. , Jacobson Samuel G. , Lewin Alfred S. , Aguirre Gustavo D. , Beltran William A.
Published: August 2018

Significance

A number of gene-augmentation strategies are entering clinical trials for the treatment of inherited retinal blindness. Gene therapy for autosomal dominant diseases faces significant obstacles that include allelic heterogeneity and the potential need to silence the mutated gene. Here we show that a single-gene therapy vector that combines knockdown of the causative gene with its replacement by a resistant wild-type copy can prevent photoreceptor cell death and vision loss in a canine model of autosomal dominant retinitis pigmentosa.
Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa
Authors: Vonaesch Pascale , Morien Evan , Andrianonimiadana Lova , Sanke Hugues , Mbecko Jean-Robert , Huus Kelsey E. , Naharimanananirina Tanteliniaina , Gondje Bolmbaye Privat , Nigatoloum Synthia Nazita , Vondo Sonia Sandrine , Kaleb Kandou Jepthé Estimé , Randremanana Rindra , Rakotondrainipiana Maheninasy , Mazel Florent , Djorie Serge Ghislain , Gody Jean-Chrysostome , Finlay B. Brett , Rubbo Pierre-Alain , Wegener Parfrey Laura , Collard Jean-Marc , Sansonetti Philippe J. ,   The Afribiota Investigators, Andriatahirintsoa Emilson Jean , Barbot-Trystram Laurence , Barouki Robert , Bastaraud Alexandra , Collard Jean-Marc , Doria Maria , Duffy Darragh , Etienne Aurélie , Finlay B. Brett , Djorie Serge Ghislain , Giles-Vernick Tamara , Gody Jean-Chrysostome , Hasan Milena , Héraud Jean-Michel , Huetz François , Hunald Francis Allan , Kapel Nathalie , Lombart Jean-Pierre , Manirakiza Alexandre , Nigatoloum Synthia Nazita , Novault Sophie , Wegener-Parfrey Laura , Raharimalala Lisette , Rakotondrainipiana Maheninasy , Randremanana Rindra , Randriamizao Harifetra Mamy Richard , Randrianirina Frédérique , Robinson Annick , Rubbo Pierre-Alain , Sansonetti Philippe , Schaeffer Laura , Gouandjika-Vassilache Ionela , Vonaesch Pascale , Vondo Sonia Sandrine , Vigan-Womas Inès
Published: August 2018

Significance

Stunting globally affects an estimated 155 million children under 5 years of age, representing about 25% of children worldwide. Due to poor understanding of the underlying pathophysiology, therapeutic interventions to efficiently correct for linear growth delay or associated pathophysiological disturbances are still lacking. Here, we describe the microbial composition of duodenal fluids from stunted children. We show that these children are affected by small intestinal bacterial overgrowth and harbor a characteristic microbial community composed mainly of oropharyngeal bacteria. This microbial signature is also reflected in their feces and conserved between countries. Stunting is traditionally considered to arise from recurrent enteric infections. This study shows that oropharyngeal taxa are associated with stunting, suggesting that alternative pathophysiological mechanisms are involved.
Gelation of plasmonic metal oxide nanocrystals by polymer-induced depletion attractions
Authors: Saez Cabezas Camila A. , Ong Gary K. , Jadrich Ryan B. , Lindquist Beth A. , Agrawal Ankit , Truskett Thomas M. , Milliron Delia J.
Published: August 2018

Significance

Self-supported gelation of optically active nanocrystals offers a modular pathway to harness optoelectronic functionality in multiscale materials by directly controlling volume fraction, bonding, and structure during assembly. We combine depletion attractions that emerge from the incorporation of small polymer chains and electrostatic repulsions to induce the gelation of isotropic metal oxide nanocrystals. We develop a theoretical model to assess our experimental fluid-to-gel-phase progression observations. By preventing nanocrystal fusion during network assembly, we achieve gels with a strong near-infrared absorption, reminiscent of the inherent near-infrared localized surface plasmon resonance of the nanocrystal building blocks.
Selective permeability of mouse blood-aqueous barrier as determined by
15
N-heavy isotope tracing and mass spectrometry
Authors: Liu Pan , Thomson Benjamin R. , Khalatyan Natalia , Feng Liang , Liu Xiaorong , Savas Jeffrey N. , Quaggin Susan E. , Jin Jing
Published: August 2018

Significance

The aqueous fluid of the eye is composed of proteins from both blood circulation and ocular production. The main filter between the blood bed and the intraocular fluid is referred to as the blood-aqueous barrier. Here we devised an approach to address the selectivity of the barrier using nitrogen-15–labeled serum proteins as tracers. Following systemic injection of the labeled serum to normal nitrogen-14 mice, the labeled proteins subsequently entered the aqueous fluid and were measured by mass spectrometry. This new quantitative method captured the dynamic redistribution patterns of approximately 500 serum proteins entering normal eye and the eye recovering from injury. We discovered inhibitory complement proteins crossed the blood-ocular barrier of the wounded eye but not of the normal eye.
Gating charge displacement in a monomeric voltage-gated proton (H
v
1) channel
Authors: Carmona Emerson M. , Larsson H. Peter , Neely Alan , Alvarez Osvaldo , Latorre Ramon , Gonzalez Carlos
Published: August 2018

Significance

H
v
1 proton channels, since their open probability increases with depolarization and low pH, are fundamental in sustaining the suitable pH gradient for cell survival. Here, we have characterized the gating current elicited by the monomeric mutant proton channel N264R with the aim of understanding the voltage-dependent processes that control channel opening. Gating currents precede ion currents, indicating that a large fraction of gating charge is displaced before H
v
1 opening. The voltage sensor displacements are complex and consist of numerous well-defined states. However, most of the charge is displaced in a single transition that probably leads to channel opening. The positively charged arginine in the N264R channel promotes gating charge trapping in addition to blocking the proton currents.
Microfluidics‐based on‐a‐chip systems for isolating and analysing extracellular vesicles
Authors: Guo Shang‐Chun , Tao Shi‐Cong , Dawn Helen
Published: August 2018

Extracellular vesicles (EVs), which can be found in almost all body fluids, consist of a lipid bilayer enclosing proteins and nucleic acids from their cells of origin. EVs can transport their cargo to target cells and have therefore emerged as key players in intercellular communication. Their potential as either diagnostic and prognostic biomarkers or therapeutic drug delivery systems (DDSs) has generated considerable interest in recent years. However, conventional methods used to study EVs still have significant limitations including the time‐consuming and low throughput techniques required, while at the same time the demand for better research tools is getting stronger and stronger. In the past few years, microfluidics‐based technologies have gradually emerged and have come to play an essential role in the isolation, detection and analysis of EVs. Such technologies have several advantages, including low cost, low sample volumes, high throughput and precision. This review summarizes recent advances in microfluidics‐based technologies, compares conventional and microfluidics‐based technologies, and includes a brief survey of recent progress towards integrated “on‐a‐chip” systems. In addition, this review also discusses the potential clinical applications of “on‐a‐chip” systems, including both “liquid biopsies” for personalized medicine and DDS devices for precision medicine, and then anticipates the possible future participation of cloud‐based portable disease diagnosis and monitoring systems, possibly with the participation of artificial intelligence (AI).
Preclinical development of anti-BCMA immunotoxins targeting multiple myeloma
Authors: Shancer Zoe , Williams Matthew , Igelman Austin , Nagata Satoshi , Ise Tomoko , Pastan Ira , Bera Tapan K
Published: August 2018

Background

Multiple myeloma (MM) is a B-cell malignancy that is incurable for the majority of patients. New treatments are urgently needed. Recombinant immunotoxins (RITs) are chimeric proteins that are composed of the Fv or Fab portion of an antibody fused to a bacterial toxin. B-cell maturation antigen (BCMA) is a lineage-restricted differentiation protein and an ideal target for antibody-based treatments for MM.

Methods

RITs were produced by expressing plasmids encoding the components of the anti-BCMA RITs in Escherichia coli followed by inclusion body preparation, solubilization, renaturation, and purification by column chromatography. The cytotoxic activity of RITs was tested in vitro by WST-8 assays. We also measured their binding to human and mouse serum albumins and to BCMA and measured their serum half-life in mice.

Results

Using Fvs from different anti-BCMA antibodies, we produced RITs that specifically kill BCMA-expressing MM cells in vitro. To increase the serum half-life in vivo, we generated RITs that are fused with albumin-binding domains (ABDs). All RITs with ABDs have some decreased activity compared to the parent RIT, which is not due to decreased binding to BCMA.

Conclusions

Various new anti-BCMA immunotoxins were produced and evaluated. None of these were better than LMB-75 (anti-BCMA BM306-disulfide-stabilized Fv-LRggs) supporting the further preclinical development of LMB-75.
Bystander inhibition of humoral immune responses by Epstein–Barr virus LMP1
Authors: Tsai Chao-Yuan , Sakakibara Shuhei , Yasui Teruhito , Minamitani Takeharu , Okuzaki Daisuke , Kikutani Hitoshi
Published: August 2018

Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), which mimics a constitutively active receptor, is required for viral transformation of primary B cells. LMP1 is expressed in EBV-infected germinal center (GC) B cells of immunocompetent individuals, suggesting that it may contribute to persistent EBV infection. In this study, we generated and analyzed mice that expressed LMP1 under the control of the CD19 or activation-induced cytidine deaminase (AID) promoter. Expression of LMP1 induced activation of B cells but severely inhibited their differentiation into antibody-secreting cells (ASCs) in vitro and GC B cells in vivo. LMP1-expressing (LMP1+) B cells not only suppressed the functions of wild-type (WT) B cells in in vitro co-culture, but also blocked differentiation of WT B cells into GC B cells and ASCs in immunized bone marrow chimeric mice. Microarray analysis revealed that the gene encoding indoleamine 2,3-dioxygenase 1 (IDO1), a major enzyme involved in the tryptophan metabolic process, was highly induced by LMP1. Either inhibition of IDO1 activity by methyl-l-tryptophan or knockout of Ido1 in LMP1+ B cells could rescue WT B cells from such suppression. IDO1-induced tryptophan consumption and production of tryptophan metabolites appeared to be responsible for inhibition of B-cell function. We conclude that LMP1 expression in antigen-committed B cells not only directly impairs GC B-cell differentiation, but also indirectly inhibits the functions of neighboring B cells, resulting in suppression of humoral immune responses. Such bystander inhibition by LMP1+ B cells may contribute to immune evasion by EBV.
Neurological paraneoplastic syndromes: an update
Authors: Berzero Giulia , Psimaras Dimitri
Published: August 2018

Purpose of review

To describe recent advances in the diagnosis and treatment of paraneoplastic neurological syndromes (PNS).

Recent findings

PNS are rare complications of cancer caused by an immune cross-reaction between antigens expressed by tumor cells and neurons. The target of the immune attack can be an intracellular antigen or a cell-surface antigen. Although both types of autoimmunity are ‘paraneoplastic’, as indirectly triggered by the presence of a tumor, they profoundly differ in terms of clinical profile, pathogenesis and outcome. PNS associated with antibodies to intracellular antigens (icPNS) are characterized by relentless progression and poor response to treatment, because of rapid and permanent neuronal loss. PNS associated with antibodies to cell-surface antigens (csPNS) generally show favorable response to immune therapy and good functional outcome, as they result from reversible neuronal dysfunction.

The spectrum of paraneoplastic autoimmunity has dramatically expanded following the discovery of cell-surface antibodies. Novel antibodies are incessantly discovered, some of which have a solid association with cancer. As csPNS usually respond to immune therapy, the optimization of current treatment strategies should have high priority to improve therapeutic results and prevent relapses.