bluuebunny/crossref_metadata_2025 huggingface dataset:
Problems of Implementing Innovative Solutions in the Construction Sector of Economy Organizations
Authors: Rakhova Maria , Nikonorova Svetlana
Published: December 2018

The subject of research in the following article is innovative solutions in organizations which are engaged in construction activity, their importance for development and increase in socio-economic indexes. In order to assess the level of innovativeness of the regional economy of the central federal district of the Russian Federation, the survey presents the dynamics of the innovation development rating of the subjects (according to the ISIEZ of the HSE). The importance of development and introduction of innovations are reflected in the construction sector of economy. As the subject of detailed research in this article, the enterprises of the Vladimir region, implementing innovative projects and development, and also dynamics of indicators of their functioning, are considered. Survey conducted within the research has allowed to allocate and group the main reasons for low innovative activity of the construction enterprises.
The Assessment of the Prospects for the Creation of a Single Economic Site in the Territory of the Central Federal District in order to Develop Cluster Elements in the Field of Construction
Authors: Rakhova Maria , Zakirova Maria
Published: December 2018

The article describes the main approaches to the definition of clusters. The signs that form the clusters of the territory are clarified, this list is supplemented with the sign “intersectoral interaction”. The main methodical approaches to the calculation of clusters are also disclosed. In the research methods of the analysis, synthesis, grouping of data and also the cluster analysis were applied. The object of survey were the regions of the Central Federal District. Based on the calculation of localization coefficients, an analysis was made of the possibility of forming a construction cluster in the investigated district or the purpose of more efficient use of regional resources.
Return on investment in the implementation of energy-efficient solutions for facade insulation
Authors: Gamaunova Olga , Musorina Tatiana
Published: December 2018

In this article the technique of determination of payback period of investments taking into account capital costs and economy of means at the expense of implementation of energy saving actions for warming of external protecting designs is considered. Presented in the article the method of assessing the return on investment in the implementation of energy-efficient solutions of facade insulation is only evaluative. For more accurate calculations it is necessary to take into account the discount rate. Nevertheless, the main factors that have a positive impact on reducing the payback period of investments in the renovation of facades are identified. Only an integrated approach to improving the energy efficiency of buildings can not only reduce the cost of operation of buildings, but also provide a reduction in the payback period of investment in the implementation of energy efficiency measures.
Main directions of “Smart city” development in the republic of Kazakhstan
Authors: Shalbolova Urpash , Kenzhegaliyeva Zita
Published: December 2018

The article focuses on paramount targets for developing “smart” cities in the Republic of Kazakhstan. The conducted studies substantiate the effectiveness of reforms in the housing and utilities sector of Kazakhstan in accordance with the branch state programs and the need for a comprehensive solution of the existing problems for the further successful development of smart cities. This study has been conducted in the framework of the project APO05134552 entitled “Economic evaluation of investment projects for the modernization of housing and communal services in the Republic of Kazakhstan”.
Shielding effect of reinforced concrete fences in electromagnetic fields of industrial frequency
Authors: Amirkhanyan Mariya , Bryukhan Fedor
Published: December 2018

Electromagnetic fields (EMF) are one of the main types of physical pollution of the environment in urban lands. The danger of adverse impact of EMF on human health increases with growth of electric power consumption. Therefore, the issues of protection of the population against EMF impact are becoming very important. One of the options for protection against EMF exposure is the use of reinforced concrete fences with shielding properties. Despite the simplicity of such a device against EMF, it can be stated that shielding effect assessment issues are poorly known. The objective of this paper is to assess the shielding effect of reinforced concrete fences in EMF industrial frequency. The shielding effect of the reinforced concrete fences study was conducted on the surrounding area of the thermal power plant (TPP), located on the edge of Mytishchi city of the Moscow Region. The effects of an abrupt increase in the EMF intensity in front of the reinforced concrete fence and its decrease behind the fence are revealed. It is found that these effects are associated with the concrete reinforcement impact inside the fence, in which an alternating electric current is generated. The shielding effect determines the partial reflection of EMF in front of the fence and decrease of EMF inside it. Accounting for the shielding effect of reinforced concrete fences provides perspectives of organizing the protection of the population near residential and industrial buildings, as well as protection of personnel working in the strong EMF areas.
Reduction of territorial fire risks based on methods of active systems theory
Authors: Minaev Vladimir , Faddeev Alexander , Dao Tuan , Tuan Anh Phan
Published: December 2018

Subject of the study: Models of relationships between specific index for the number of deaths and injuries in fires and specific load by fires are studied. A complex specific indicator (the number of deaths and injuries in fires) is formed. Thereupon, based on the principles of active systems theory, a target function for optimal territorial distribution of human resources of fire service in clusters – groups of homogeneous provinces in terms of fire risks – is constructed.

Goal of the study: The article is aimed at justifying and constructing complex criteria for optimal management of the human resources of the fire service.

Materials and methods: Methodological basis for fire risks assessment is the integral fire risks theory, and human resources management is the theory of active systems. The dynamics of fire risk indicators in Vietnam from 2006 to 2016 is considered.

Results: The optimal distribution of human resources allows a 10-12% reduction in the complex specific indicator of risks.

Conclusions: The obtained solutions make it possible to develop practical recommendations for authorities, industries, including construction industry, and fire service, on improving management of territorial human resources taking into account fire risks, enhancing legal and regulatory support for insurance in construction industry.
Safe operation and reconstruction of urban water bodies in the park complexes
Authors: Plyusnina Yekaterina , Ostiakova Aleksandra
Published: December 2018

In the field of improvement of urban areas of General use, it is important to study the environmental problems of urban water bodies and to ensure the necessary level of sanitary maintenance and improvement of the water bodies themselves and the surrounding area. This article investigates the ecological state of the city pond in the park of Nakhabino in the Moscow region. At the moment, the condition of the pond is unsatisfactory in terms of both improvement and sanitary-hygienic and aesthetic condition. The purpose of the work is to analyze the existing negative environmental factors on the example of a water body, as well as to offer an option of ecological reconstruction and further safe operation. To achieve this goal, the analysis of available literature sources was carried out, a visual survey of the water body located in the Park was carried out. The article presents a description of the area of the pond and the Park, identified and listed the negative, influencing the contamination of pond and water quality factors. The necessary types of works on improvement and sanitary cleaning of the bowl of the pond and the coastal area are listed. As a result of a comprehensive analysis of the ecological status of the pond, a model of the pond named after Karbyshev in Nakhabino was created, a version of its ecological reconstruction was proposed. The model is presented at the Moscow youth exhibition. The conducted research has a certain practical value. Subsequently, it is planned to present the project of ecological reconstruction of this water body for its reconstruction to the territorial authorities.
Hook evolution and inclusion entrapment during initial solidification process of continuous casting slab
Authors: Pengcheng Xiao , Xiaoyan Wu , Liguang Zhu , Zengxun Liu
Published: December 2018

A two-dimensional numerical model was established to describe the mechanism of hook formation and evolution during the initial solidification process of continuous casting slab. Melting, coarsening, growing, and burying stages were observed to follow hook formation at the meniscus. The coordinates at which the hook was finally buried into the shell were determined for different casting speeds and pouring temperatures. The final hook depth was predicted to be approximately 1.8–2.9 mm, which was confirmed by metallographic experiments. A physical model was established based on the calculated shell shape, and the process by which the inclusions were entrapped by the hook structure was investigated. The results indicated that the floating inclusions were most likely entrapped under the nascent hook, and the inclusions gathering near the meniscus were easily captured by the upper part of the nascent hook when overflow of the molten steel occurred. The hook-like structure increased the area of the shell inner face, which resulted in swirling flow of the molten steel near the shell and increased the probability of the inclusions being captured.
Cardiomyopathies and Congenital Heart Disease in Pregnancy
Authors: Westhoff-Bleck Mechthild , Hilfiker-Kleiner Denise , Pankuweit Sabine , Schieffer Bernhard
Published: December 2018

Pregnancy-associated diseases of the cardiovascular system occur in up to 10% of all pregnancies and the incidence is increasing. Besides congenital heart disease or pre-existing cardiomyopathy in the mother, the clinical focus has moved especially to peripartum cardiomyopathy (PPCM) because of the conditionʼs dramatic clinical course and the identification of the underlying mechanisms. This review article concentrates therefore on PPCM, which occurs either in the last month of pregnancy or in the first 6 months following delivery in women with previously healthy hearts. The global incidence is estimated today at roughly 1 : 1000 pregnancies. The condition is heterogeneous, ranging from mild disease to severe acute heart failure with cardiogenic shock and sudden cardiac death of the mother. Important risk factors are pregnancy-associated hypertensive complications, multiple pregnancy and greater maternal age. The pathogenesis comprises cleavage, induced by increased oxidative stress, of the lactation hormone prolactin into a toxic hormone fragment that damages blood vessels, known as the 16-kDalton protein fragment. The lactation-blocking drug bromocriptine prevents prolactin release and promotes healing of PPCM in combination with pharmacological heart failure therapy; it appears to prevent recurrence in subsequent pregnancies. Uncomplicated pregnancy is possible in most patients with congenital heart disease. The foetal complications include an increased abortion rate, prematurity and smallness for gestational age, as well as an increased risk of cardiac malformations. The maternal risk comprises mainly arrhythmias, progressive heart failure and thrombembolic complications, with the risk of vessel dissection with a low mortality risk of < 1% in the case of aortopathies. Individual risk assessment and corresponding close monitoring of the pregnancy are required.
Semiconductor nanowires improve the performance of energy conversion devices
Authors: Fellet Melissae
Published: December 2018

Controlling the growth and composition of nanowires is key to building photovoltaics, thermoelectrics and betavoltaics with optimal performance.
Organic production.
Authors: Soler A. , Reinhardt D. H. , Matos A. P. de , Pádua T. R. P. de
Published: December 2018

While there is a considerable body of published literature on organic farming, there is little dedicated to pineapple. A recent publication of note, La Piña, reviews organic production of pineapple. Also, Embrapa has recently made available recommendations for organic production of pineapple in Brazil based upon studies in the Chapada Diamantina region, a tropical highland of the State of Bahia. This chapter discusses the specifications and certifications for organic production of pineapple; the organic cultural systems, focusing on integrated pest, disease and weed management; spatial organization of the plots; plant nutrition; flower initiation; pre-harvest fruit treatments; harvesting; and postharvest systems. Organic production of pineapple is feasible but most easily on a small scale in a mixed cropping situation. Government, consumer and grower interest is, however, increasing and this can only help to encourage further research in this field.
Justice Speaks, but Who's Listening?
Authors: Hitt Matthew P. , Saunders Kyle L. , Scott Kevin M.
Published: December 2018

We seek to measure the impact of decisions issued by the US Supreme Court on public awareness of its cases. We use a quasi-experimental design with the Court decisions as the stimulus of hypothesized public awareness change. We find that public awareness of cases varies according to individual differences: more educated, knowledgeable, and informationally motivated citizens are more likely to report awareness. Further, decision announcements increase awareness more generally, especially in cases of moderate salience. In contrast, for a very high salience case, awareness is high before and after the decision is announced, while, for a case fabricated by the investigators, “awareness” is not affected by the Court’s activities. The results suggest that while the public may eventually respond to the behavior of national institutions, this response is likely first filtered through an elite subset of the population.
The Enduring Relevance of Karl Marx
Authors: Prew Paul , Rotta Tomás , Smith Tony , Vidal Matt
Published: December 2018

This chapter is the introduction to The Oxford Handbook of Karl Marx. It demonstrates the continuing applicability of Marx’s concepts and theories to understanding twenty-first century capitalism, its crises, and the historical development of human society across varying modes of production. It presents an intellectual biography linking the major moments in Marx’s life to his ideas and theories. The biography also gives insight into Marx’s approach to research by focusing more closely on the method he outlined in the Grundrisse. It demonstrates, among other things, that Marx continually revised his ideas in light of new evidence or theoretical understanding. The chapter concludes with brief summaries of the handbook’s contributions, paying specific attention to the ongoing relevance of each chapter to societal concerns. While the introduction introduces the reader to the varied chapters in the handbook, it goes beyond mere summary to provide fresh insight into Marx’s life, work, and promise.
Gentrification and Urban Inequality
Authors: Ocejo Richard E.
Published: December 2018

This chapter explores the relationship between consumption, gentrification, and inequality in today’s city, specifically how consuming and aesthetic taste are becoming intertwined with the process in ways that are presenting new implications for understanding urban inequality. Consumption has been a significant theoretical and empirical focus in the gentrification literature, and this chapter builds on the argument that scholars should consider it as being intertwined with production to understand how the process plays out in different contexts. Although gentrification has often followed relatively predictable patterns in its unfolding, this chapter uses two examples—“food mirages” and the mobility of the process’s advanced stage—to show how new patterns are complicating long-held theories. The chapter encourages further research into how these relatively recent developments are conditions of inequality in many of today’s cities.
Taste, Legitimacy, and the Organization of Consumption
Authors: Maguire Jennifer Smith
Published: December 2018

This chapter reviews the ways in which the social phenomena of legitimation and taste organize consumption practices and entities into recognizable, repeated patterns. A bird’s eye view of legitimation outlines the interrelationships between higher level, encompassing frameworks, legitimacy frames and devices, and the internalization of common social structures in the organization of social action. The discussion then looks at taste in more detail, proposing gravitation as a novel metaphoric lens for understanding the normative, conventional, and habitual dynamics that pull individual consumers and consumption entities into the macro structures of styles, lifestyles, markets, and fields.
Manufacturing Growth and Structural Change in American Economic History
Authors: Lee Changkeun , Rhode Paul W.
Published: December 2018

Over past 200 years, industrialization was the driving force in the economic development of most nations experiencing “modern economic growth.” Industrial activity generally expanded faster than the economy as a whole, and the sector grew to account for sizable shares of output, employment, and trade. Manufacturing activities have generally experienced faster rates of productivity growth than the economy as a whole and the sector has often paid higher labor wages. Manufacturing also contributes materiel and technology for military purposes. For these reasons, policymakers and the public have long viewed manufacturing as being of greater importance than other activities. This chapter surveys growth and structural change in the American manufacturing sector over the past 200 years. It chronicles the sector’s transformation during the first (1810–1860), second (1870–1920), and third (1970–present) industrial revolutions. It examines the forces, such as globalization, information technologies, and deindustrialization, shaping the sector today.
Antitrust and Regulation in American Economic History
Authors: Kaiser Brooks
Published: December 2018

Over the course of American history and economic development, market activity and the systems underlying and governing this activity have coevolved to address the changing fundamentals of human interactions within the marketplace and beyond. The growth of the American economy and its regulation are deeply intertwined. This chapter discusses these coevolutionary forces in the context of the development of American antitrust laws and the expanding reach of government regulation throughout American economic history. Antitrust and regulation are addressed together because they complement each other in their ability to address ex-ante incentives, primarily through regulation, and ex-post corrections and adjustments, primarily through antitrust suits and related legislative action, that may in turn result in new regulation. The chapter focuses on government regulation of industry in two arenas: price and entry regulation with market power (antitrust issues), and regulation of other market failures, especially environmental, health, occupational safety, and product quality regulation.
Introduction
Authors: Meibauer Jörg
Published: December 2018

Based on a thorough review of recent literature on lying and deception, the introduction gives accessible answers to five basic research questions. For the first question—how can lying be defined?—it considers definitions of lying given in the philosophy of language and in linguistics. For the second question—how can lying be detected?—it addresses psychological research on detection of lying. Psychology and neuroscience are the most important disciplines with respect to the third question, concerning the processing of lying. The fourth question—how is lying acquired?—is dealt with in psycholinguistics. Finally, the ethical question of lying—how is lying evaluated?—is discussed. Since answers to these questions are typically given by linguistics, philosophy, and psychology, the chapter suggests that an integrative approach to lying will be drawing heavily on these disciplines.
Lying and Computational Linguistics
Authors: van Deemter Kees , Reiter Ehud
Published: December 2018

This chapter espouses an engineering perspective on lying, showing how various departures from the truth arise naturally when computers talk about data. We start by explaining how Natural Language Generation (NLG) systems work when they talk about data. Then we discuss how, perhaps surprisingly, such systems cannot help deviating from the truth in two different ways, namely, by omitting information, and by generating statements whose truth is questionable; we illustrate our account with examples from practical NLG systems. Next, we discuss briefly why NLG systems should arguably deviate from the truth in other, more deliberate ways as well, after which we sketch a simple game-theoretical model that can help to explain our observations. We conclude by summing up what the engineering view tells us about lying, whether it is people or computers that take the floor.
Linguistic Approaches to Lying and Deception
Authors: Hardin Karol J.
Published: December 2018

This chapter examines approaches to lying and deception within a linguistic framework by studying lying as it relates to phonetics, phonology, morphology, syntax, semantics, and pragmatics. It details empirical research on linguistic cues to lying, the emergence of lying, and attitudes to lies in different cultures. Both intercultural and cross-cultural studies are included, most of which contrast English with other languages. Coleman and Kay’s seminal work on the semantics of lying and replication studies in Arabic and Spanish are of particular interest. Finally, applied research in various discourse genres such as media language, politics and propaganda, and online discourse are presented. The chapter demonstrates how lying is a pragmalinguistic and sociolinguistic phenomenon that is best understood through empirical studies, ones providing insights into lying in real-life language situations.
Lying, Deception, and the Brain
Authors: Decker Alexa , Disney Amanda , D'elia Brianna , Keenan Julian P.
Published: December 2018

Deception is a common behavioral phenotype across species. Homo sapiens deceive at an excessive rate and in a manner that is truly unique. While the neural correlates for deception are fairly well known, larger questions remain, such as when did these neural networks emerge, and did deception have anything to do with the emergence of these specific neural substrates? Furthermore, little is known about the neural substrates of self-deception and the evolution of these networks. The summary of our knowledge is presented, with a strong emphasis on the social and metacognitive pressures that deception has put on human evolution. Future research possibilities are also discussed.
Lying, Belief, and Knowledge
Authors: Benton Matthew A.
Published: December 2018

What is the relationship between lying, belief, and knowledge? Most philosophical accounts of lying define it in terms of belief, namely telling someone something that one believes to be false, often with the intent to deceive. This chapter develops a novel account of lying by deriving evaluative dimensions of responsibility from the knowledge norm of assertion. On these dimensions, we can distinguish reasonable assertions, negligent assertions, and vicious assertions. On the definition of lying defended here, lies are best understood as special cases of vicious assertion; thus lying is the anti-paradigm of proper assertion. This enables an account of lying in terms of knowledge rather than belief: roughly, lying is telling someone something you know ain’t so.
Self
Authors: Zahavi Dan
Published: December 2018

Self presents phenomenological work on selfhood and shows how it has been impacting phenomenological psychopathology. Most phenomenologists including Husserl, Heidegger, and Sartre would defend the experiential presence of self, thereby distancing themselves from competing accounts according to which the self is either a high-level social construct or a hidden non-experiential transcendental precondition. Many also highlighted the deep link between selfhood and self-consciousness, and between self-consciousness and intentionality, thereby defending the “co-givenness of self and world.” Eventually, however, most phenomenologists went on to emphasize the extent to which a more comprehensive account of selfhood would have to move beyond a purely formal analysis and also consider the individualizing role of historicity, sociality, and normativity.
Technique of Fractionated Transcatheter Arterial Embolization for Treating Large Arteriovenous Malformation in Brain Functional Area
Authors: Ma Jun , Lu Hua , Wu Wei , Li Zheng , Wang Xiefeng , Zhu Haifeng , Liu Ning
Published: December 2018

Objective:

At present, large cranial function area arteriovenous malformation (fAVM) is mainly treated by craniotomy with a high risk of operation and high disability. In recent years, with the continuous improvement of the neural intervention technology, fractionated transcatheter arterial embolization (fTAE) may be used to treat the fAVM instead of surgical treatment. However, its effectiveness for treating fAVM has never been explored. The authors hypothesized that fTAE can be effective in the treatment of fTAE.

Methods:

A retrospective study was conducted in 229 cases of large fAVM in multicenter hospitals. Among them, 103 cases were performed fTAE and the other 126 cases were carried on minimally invasive craniotomy (MIC). Clinically relevant symptomatic improvement and complications were compared between 2 groups.

Results:

Complete resection rate of arteriovenous malformation in MIC group (100%) was significantly higher than that of complete embolization rate in fTAE group (77.7%) (P = 0.000). However, the incidence of postoperative complications includes decreased limb muscle strength (P = 0.001), sensory loss of extremities (P = 0.003), visual field defect (P = 0.025) that were lower in fTAE group and remission rate of headache (P = 0.012) but not epilepsy (P = 0.952) was higher in fTAE group compared with that in MIC group. After 1 year follow-up, the rebleeding rate in the fTAE treatment group was 4.85%, higher than that in MIC group (0%) (P = 0.000).

Conclusions:

Fractionated transcatheter arterial embolization therapy is beneficial for reducing the postoperative complications and preoperative symptoms of fAVM, but not for recurrence rate.
Septoplasty Under Local Anesthesia
Authors: Obradovic Bojan
Published: December 2018

Septoplasty is usually performed under general anesthesia or local anesthesia with sedation. Nevertheless, septoplasty under pure local anesthesia is also feasible and it shows a great potential for fast-track surgery. This article presents a patient with nasal septal deviation where septoplasty was managed under local anesthesia at an outpatient clinic. Treatment and postoperative period were routine. Septoplasty under local anesthesia showed a great potential in adequately selected patient.
Dissection of intestines from larval zebrafish for molecular analysis
Authors: San Bilge , Aben Marco , Flik Gert , Kamminga Leonie M.
Published: December 2018

Epigenetic data obtained from whole zebrafish embryos or larvae may mask or dilute organ-specific information. Fluorescence activated cell sorting can diverge cells from their native state, and cryosections often yield insufficient material for molecular analysis. Here, we present a reproducible method for larval intestinal isolation at 5, 7, and 9 days post-fertilization, using the intestine-specific transgenetgBAC(cldn15la:GFP). With tweezers, the intestine can be pulled out of the abdomen in one smooth motion. Upon removal of adhering tissues, intestines can be directly used for analyses. Each dissection takes 3-6 minutes per fish. We demonstrate that 10 and 25 dissected intestines yield enough material for RNA-sequencing and ChIP-sequencing, respectively. This method results in high quality, live material, suitable for many downstream applications.

METHOD SUMMARY

We present a reproducible method for zebrafish larval intestinal isolation which results in high quality, live material. With tweezers, the intestine can be pulled out of the abdomen and after removal of adhering tissues, intestines can be directly used for analyses. We demonstrate that 10 and 25 dissected intestines yield enough material for RNA-sequencing and ChIP-sequencing, respectively.
Optimizing the use of the Men-ACWY conjugated vaccine to control the developing meningococcal W disease outbreak in the Netherlands, a rapid analysis
Authors: van Hoek Albert Jan , Knol Mirjam , de Melker Hester , Wallinga Jacco
Published: December 2018

Background

There is a developing outbreak of Neisseria meningitidis serotype W (MenW) in the Netherlands. In response, those aged 14 months and 14 years are vaccinated with the conjugated MenACWY vaccine. In the spring of 2018 we aimed to explore the impact of adding a one-off catch-up campaign targeting those aged 15-18 years on the transmission of MenW and the cost-effectiveness of such a campaign.

Methods

We estimated the growth rate of the MenW outbreak and quantified the impact of various targeted vaccination strategies on the reproductive number, and subsequently projected the future incidence with and without vaccination. Future cases were expressed in costs and QALYS and the incremental cost-effectiveness ratio was obtained.

Results

We estimate a reproductive number of around 1.4 (95%CI 1.2-1.7) over the period February 2016-February 2018. Adding the catch-up campaign reduces the reproductive number five years earlier than without a catch-up campaign, to a level around 1.2. The vaccination campaign, including the catch-up, will prevent around 100 cases per year in our base case scenario. Given the projected impact and realistic assumptions on costs and QALYs, adding the catch-up can be considered cost-effective using a threshold of €20,000 per QALY.

Conclusion

Adding the catch-up campaign targeting those aged 15-18 brings the impact of vaccination on reducing transmission five years forward and directly prevents a high-incidence age group from carriage and disease. Such a campaign can be considered cost-effective. Our study did underpin the decision to introduce a catch-up campaign in spring 2019. Furthermore, our applied method can be of interest for anyone solving vaccine allocation questions in a developing outbreak.
New insights from 22-kHz ultrasonic vocalizations to characterize fear responses: relationship with respiration and brain oscillatory dynamics
Authors: Dupin Maryne , Garcia Samuel , Boulanger-Bertolus Julie , Buonviso Nathalie , MOULY Anne-Marie
Published: December 2018

Fear behavior depends on interactions between the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA), and the expression of fear involves synchronized activity in theta and gamma oscillatory activities. In addition, freezing, the most classical measure of fear response in rodents, temporally coincides with the development of sustained 4-Hz oscillations in prefrontal-amygdala circuits. Interestingly, these oscillations were recently shown to depend on the animal's respiratory rhythm, supporting the growing body of evidence pinpointing the influence of nasal breathing on brain rhythms. During fearful states, rats also emit 22-kHz ultrasonic vocalizations (USV) which drastically affect respiratory rhythm. However, the relationship between 22-kHz USV, respiration and brain oscillatory activities is still unknown. Yet such information is crucial for a comprehensive understanding of how the different components of fear response collectively modulate rat's brain neural dynamics. Here we trained male rats in an odor fear conditioning task, while recording simultaneously local field potentials in BLA, mPFC and olfactory piriform cortex, together with USV calls and respiration. We show that USV calls coincide with an increase in delta and gamma power and a decrease in theta power. In addition, during USV emission in contrast to silent freezing, there is no coupling between respiratory rate and delta frequency, and the modulation of fast oscillations amplitude relative to the phase of respiration is modified. We propose that sequences of USV calls could result in a differential gating of information within the network of structures sustaining fear behavior, thus potentially modulating fear expression/memory. Significance Statement: While freezing is the most frequently used measure of fear, it is only one amongst the different components of rodents' response to threatening events. USV is another index that gives additional insight into the socioemotional status of an individual. Our study is the first to describe the effects of USV production on rat's brain oscillatory activities in the fear neural network, and to relate some of them to changes in nasal breathing. A better knowledge of the impact of USV calls on brain neural dynamics is not only important for understanding the respective weight of the different components of fear response, but is also particularly relevant for rodent models of human neuropsychiatric disorders, for which socio-affective communication is severely impaired.
Environmental disorder can tip the population genetics of range expansions
Authors: Gralka Matti , Hallatschek Oskar
Published: December 2018

Evolutionary dynamics is fundamentally shaped by stochastic processes: spontaneous mutations enter populations randomly, and the fate of a mutant lineage is determined by the competition between (random) genetic drift and (deterministic) selection. In populations undergoing range expansions, fluctuations in the reproductive process and the local motion of individuals are enhanced within a small subpopulation at the edge of the population. Range expansions are typically studied in homogeneous environments, but we argue here that the fluctuations at the range edge are susceptible to small-scale environmental heterogeneities that may have a strong effect on the evolutionary dynamics of the expanding population.

To show this, we tracked the dynamics of the clones of spontaneous mutations with a tunable fitness effect in bacterial colonies grown on randomly disordered surfaces. We find that environmental heterogeneity on scales much larger than an individual, but much smaller than the total population, can dramatically reduce the efficacy of selection. Time lapse microscopy and computer simulations suggest that this effect is a general consequence of a local "pinning" of the expansion front, whereby stretches of the front are slowed down on a length scale that depends on the structure of the environmental heterogeneity. This pinning focuses the range expansion into a small number of individuals with access to expansion paths, increasing the importance of chance and thus limiting the efficacy of selection.
The effect of carnitine on preservation of renal cold ischemia in rats
Authors: Aslaner Arif , Gunal Omer , Turgut Hamdi Taner , Yildirim Umran
Published: December 2018

Background: Although, University of Wisconsin (UW) solution is referred to as the gold standard for the preservation from cold ischemia, studies that aiming to protract the cold ischemia time still goes on. This study was planned to evaluate the effectiveness of carnitine that is added to UW solution on renal cold ischemia time.
Methods: Thirty two male Wistar Albino rats were divided into four groups of 8 each; Control, UW, carnitine with Ringer Lactate (RL) and UW groups. Retrieved renal grafts were preserved in solutions at +4C after perfusion. At the same time tissue samples of 72th hour was assessed to measure Malondialdehyde (MDA) levels. Preservation solution samples were assessed at 0th, 24th, 48th, and 72th hours to measure Lactate Dehydrogenase (LDH) activity. Tissue injury was histologically scored by evaluating the hematoxilen-eosin stained paraffin sections.
Results: Administration of carnitine to preservation solutions decreased the mean tissue MDA levels in groups 2 and 4. Carnitine administration slowed the increase of LDH levels in preservation solutions as well as the histopathological total tissue injury scores.
Discussion: We conclude that the addition of carnitine to UW solution increased the preventive effect of preservative solution on cold ischemia injury of kidney.
Keywords: Kidney; Cold Preservation; University of Wisconsin; Ringer Lactate
Disruption of IRElα through its Kinase Domain Attenuates Multiple Myeloma
Authors: Harnoss Jonathan M , Thomas Adrien Le , Marsters Scot A , Lawrence David A , Lu Min , Chen Yung-Chia Ariel , Qing Jing , Totpal Klara , Kan David , Segal Ehud , Wallweber Heidi Ackerly , Wang Weiru , Clark Kevin , Kaufman Susan , Beresini Maureen , Sandoval Wendy , Lorenzo Maria , Wu Jiansheng , Ly Justin , Bruyn Tom De , Heidersbach Amy , Haley Benjamin , Gogineni Alvin , Weimer Robby , Lee Dong , Braun Marie-Gabrielle , Rudolph Joachim , VanWyngarden Michael J , Sherbenou Daniel W , Gomez-Bougie Patricia , Amiot Martine , Acosta-Alvear Diego , Walter Peter , Ashkenazi Avi
Published: December 2018

Multiple myeloma (MM) arises from malignant immunoglobulin-secreting plasma cells and remains an incurable, often lethal disease despite recent therapeutic advances. The unfolded-protein response sensor IRE1α supports protein secretion by deploying a kinase-endoribonuclease module to activate the transcription factor XBP1s. MM cells may coopt the IRE1α-XBP1s pathway; however, the validity of IRE1α as a potential MM therapeutic target is controversial. Here we show that genetic disruption of IRE1α or XBP1s, or pharmacologic IRE1α kinase inhibition, attenuated subcutaneous or orthometastatic growth of MM tumors in mice, and augmented efficacy of two well-established frontline antimyeloma agents, bortezomib or lenalidomide. Mechanistically, IRE1α perturbation inhibited expression of key components of the ER-associated degradation machinery, as well as cytokines and chemokines known to promote MM growth. Selective IRE1α kinase inhibition reduced viability of CD138+ plasma cells while sparing CD138− cells from bone marrow of newly diagnosed MM patients or patients whose disease relapsed after 1 - 4 lines of treatment in both US- and EU-based cohorts. IRE1α inhibition preserved survival and glucose-induced insulin secretion by pancreatic microislets. Together, these results establish a strong therapeutic rationale for targeting IRE1α with kinase-based small-molecule inhibitors in MM.

Significance statement

Multiple myeloma (MM) is a lethal malignancy of plasma cells. MM cells have an expanded endoplasmic reticulum (ER) that is constantly under stress due to immunoglobulin hyperproduction. The ER-resident sensor IRE1α mitigates ER stress by expanding the ER’s protein-folding capacity while supporting proteasomal degradation of misfolded ER proteins. IRE1α elaborates these functions by deploying its cytoplasmic kinase-RNase module to activate the transcription factor XBP1s. The validity of IRE1α as a potential therapeutic target in MM has been questioned. Using genetic and pharmacologic disruption in vitro and in vivo, we demonstrate that the IRE1α-XBP1s pathway plays a critical role in MM growth. We further show that IRE1α’s kinase domain is an effective and safe potential small-molecule target for MM therapy.
Compensation-Related Utilization of Neural Circuits Hypothesis Model in Response Inhibition in Premanifest Huntington's Disease
Authors: Soloveva Maria V. , Jamadar Sharna D. , Hughes Matthew , Velakoulis Dennis , Poudel Govinda , Georgiou-Karistianis Nellie
Published: December 2018

During premanifest stages of Huntington's disease (pre-HD), individuals typically show increased functional brain activity thought to compensate for widespread brain anomalies. What remains unknown, is to disentangle whether increased functional brain activity reflects compensation or whether it is more of a product of HD-related pathological processes. We used a quantitative model of compensation, known as the CRUNCH (Compensation-Related Utilization of Neural Circuits Hypothesis), to characterise compensatory function in pre-HD using functional magnetic resonance imaging (fMRI). To test CRUNCH predictions, pre-HD individuals (n = 15) and age- and gender-matched controls (n = 15) performed a modified stop-signal task that incremented in four levels of stop difficulty (low, intermediate-1, intermediate-2, and high). Our results did not support the critical assumption of the CRUNCH model - controls did not show increased fMRI activity with increased level of stop difficulty. By contrast, controls showed decreased fMRI activity with increased stop difficulty in right inferior frontal gyrus pars triangularis and right caudate nucleus. Relative to controls, pre-HD individuals showed increased fMRI activity in right inferior frontal gyrus pars triangularis at intermediate-2 and high level of stop difficulty, which is the opposite effect to that predicted by the CRUNCH model. Contrary to the CRUNCH prediction, the pre-HD group showed decreased fMRI activity in right caudate nucleus at low level of stop difficulty, compared with controls. Further to this, fMRI activity patterns in right inferior frontal gyrus pars triangularis and right caudate nucleus were not accompanied by a decline in the number of successful behavioural stops in pre-HD. We therefore suggest that the CRUNCH model does not apply to characterise compensatory processes associated with response inhibition in pre-HD.
Identifying the Biosynthetic Gene Cluster for Triacsins with anN-hydroxytriazene Moiety
Authors: Twigg Frederick F. , Cai Wenlong , Huang Wei , Liu Joyce , Sato Michio , Perez Tynan J. , Geng Jiaxin , Dror Moriel J. , Montanez Ismael , Tong Tate L. , Lee Hyunsu , Zhang Wenjun
Published: December 2018

Triacsins are a family of natural products containing an N-hydroxytriazene moiety not found in any other known secondary metabolites. Though many studies have examined the biological activity of triacsins in lipid metabolism, the biosynthesis of triacsins has remained unknown. Here, we report the identification of the triacsin biosynthetic gene cluster inStreptomyces aureofaciensATCC 31442. Bioinformatic analysis of the gene cluster led to the discovery of the tacrolimus producerStreptomyces tsukubaensisNRRL 18488 as a new triacsin producer. In addition to targeted gene disruption to identify necessary genes for triacsin production, stable isotope feeding was performedin vivoto advance the understanding of N-hydroxytriazene biosynthesis.
Sustainability of spatially distributed bacteria-phage systems
Authors: Eriksen Rasmus Skytte , Mitarai Namiko , Sneppen Kim
Published: December 2018

Virulent phages can expose their bacterial hosts to devastating epidemics, in principle opening for a complete elimination of their hosts. Although experiments indeed confirm large reduction of susceptible bacteria, there is no reports of complete extinctions. We here address this phenomenon from the perspective of spatial organization of bacteria and how this can influence the final survival of them. By modeling the transient dynamics of bacteria and phages when they are introduced into an environment with finite resources, we quantify how the spatial separation of initial bacterial positions and the self-protection of bacteria growing in spherical colonies favor bacterial survival. This suggest that spatial structures on the millimeter scale plays an important role in maintaining microbial diversity.
Genealogical distances under low levels of selection
Authors: Huss Elisabeth , Pfaffelhuber Peter
Published: December 2018

For a panmictic population of constant size evolving under neutrality, Kingman’s coalescent describes the genealogy of a population sample in equilibrium. However, for genealogical trees under selection, not even expectations for most basic quantities like height and length of the resulting random tree are known. Here, we give an analytic expression for the distribution of the total tree length of a sample of sizenunder low levels of selection in a two-alleles model. We can prove that trees are shorter than under neutrality under genic selection and if the beneficial mutant has dominanceh< 1/2, but longer forh> 1/2. The difference from neutrality is 𝒪 (α2) for genic selection with selection intensityαand 𝒪 (α) for other modes of dominance.
RAD-sequencing for estimating GRM-based heritability in the wild: a case study in roe deer
Authors: Gervais L , Perrier C , Bernard M , Merlet J , Pemberton J , Pujol B , Quéméré E
Published: December 2018

Estimating the evolutionary potential of quantitative traits and reliably predicting responses to selection in wild populations are important challenges in evolutionary biology. The genomic revolution has opened up opportunities for measuring relatedness among individuals with precision, enabling pedigree-free estimation of trait heritabilities in wild populations. However, until now, most quantitative genetic studies based on a genomic relatedness matrix (GRM) have focused on long-term monitored populations for which traditional pedigrees were also available, and have often had access to knowledge of genome sequence and variability. Here, we investigated the potential of RAD-sequencing for estimating heritability in a free-ranging roe deer population for which no prior genomic resources were available. We propose a step-by-step analytical framework to optimize the quality and quantity of the genomic data and explore the impact of the SNP calling and filtering processes on the GRM structure and GRM-based heritability estimates. As expected, our results show that sequence coverage strongly affects the number of recovered loci, the genotyping error rate and the amount of missing data. Ultimately, this had little effect on heritability estimates and their standard errors, provided that the GRM was built from a minimum number of loci (above 7000). GRM-based heritability estimates thus appear robust to a moderate level of genotyping errors in the SNP dataset. We also showed that quality filters, such as the removal of low-frequency variants, affect the relatedness structure of the GRM, generating lower h2 estimates. Our work illustrates the huge potential of RAD-sequencing for estimating GRM-based heritability in virtually any natural population.