bluuebunny/crossref_metadata_2025 huggingface dataset:
Modified recipe to inhibit GSK-3 for the living fungal biomaterial manufacture
Authors: Jinhui Chang , Chan Kathy PoLam , Xie Yichun , Ma Ka Lee , Kwan Hoi Shan
Published: December 2018

Living fungal mycelium with suppressed or abolished fruit-forming ability is a self-healing substance particularly valuable biomaterial for further engineering and development in applications such as monitoring/sensing environmental changes and secreting signals. The ability to suppress fungal fruiting is also a useful tool for maintaining stability (e.g., shape, form) of a mycelium-based biomaterial with ease and lower cost.
The objective of this present study is to provide a biochemical solution to regulate the fruiting body formation to replace heat killing of mycelium during production. We discovered that GSK-3 activity directly correlates with the development of fruiting bodies in fungi, especially mushroom forming fungi such as Coprinopsis cinerea. By regulating GSK-3 expression and activity, one can control the fungal fruiting body development.
We successfully demonstrated that treatment of an inhibitor of GSK-3 kinase activity resulted in acceleration in mycelium growth rate, absence of fruiting body and general decrease in GSK-3 gene expression. Therefore, GSK-3 inhibitor is suggested to be included in the mycelium cultivation recipes for regulating the growth of fungal mycelium and for inhibiting the development of fruiting bodies. This is the first report of using a GSK-3 inhibitor, such as lithium or any other GSK-3 inhibitor, to suppress or abolish fruiting body formation in living fungal mycelium-based biomaterial. It also provides an innovative strategy for easy, reliable, and low cost maintenance of biomaterial containing live fungal mycelium.
A new diffractometer for diffuse scattering studies on the ID28 beamline at the ESRF
Authors: Girard A. , Nguyen-Thanh T. , Souliou S. M. , Stekiel M. , Morgenroth W. , Paolasini L. , Minelli A. , Gambetti D. , Winkler B. , Bosak A.
Published: December 2018

A new diffractometer is now available to the general user community at the ESRF. The new diffractometer is a side station of the high-resolution inelastic X-ray scattering spectrometer on beamline ID28 and is located in the same experimental hutch. Both instruments can be operated simultaneously. The new diffractometer combines a fast and low-noise hybrid pixel detector with a variable diffraction geometry. The beam spot on the sample is 50 µm × 50 µm, where focusing is achieved by a combination of Be lenses and a KB mirror. Wavelengths from 0.5 to 0.8 Å can be used for the diffraction experiments. The setup is compatible with a variety of sample environments, allowing studies under non-ambient conditions. The diffractometer is optimized to allow a rapid survey of reciprocal space and diffuse scattering for the identification of regions of interest for subsequent inelastic scattering studies, but can also be employed as a fully independent station for structural studies from both powder and single-crystal diffraction experiments. Several software packages for the transformation and visualization of diffraction data are available. An analysis of data collected with the new diffractometer shows that the ID28 side station is a state-of-the-art instrument for structural investigations using diffraction and diffuse scattering experiments.
The influence of nitrogen doping on the electronic structure of the valence and conduction band in TiO2
Authors: Wojtaszek Klaudia , Wach Anna , Czapla-Masztafiak Joanna , Tyrala Krzysztof , Sá Jacinto , Yıldız Özer Lütfiye , Garlisi Corrado , Palmisano Giovanni , Szlachetko Jakub
Published: December 2018

X-ray emission spectroscopy (XES) and X-ray absorption spectroscopy (XAS) provide a unique opportunity to probe both the highest occupied and the lowest unoccupied states in matter with bulk sensitivity. In this work, a combination of valence-to-core XES and pre-edge XAS techniques are used to determine changes induced in the electronic structure of titanium dioxide doped with nitrogen atoms. Based on the experimental data it is shown that N-doping leads to incorporation of the p-states on the occupied electronic site. For the conduction band, a decrease in population of the lowest unoccupied d-localized orbitals with respect to the d-delocalized orbitals is observed. As confirmed by theoretical calculations, the N p-states in TiO2 structure are characterized by higher binding energy than the O p-states which gives a smaller value of the band-gap energy for the doped material.
Responsible investment at Old Mutual: a case of institutional entrepreneurship
Authors: Giamporcaro Stephanie , Leslie David
Published: December 2018

Learning outcomes

To understand the motivations for adopting RI practices for institutional investors and asset managers; to understand the different RI strategies available to institutional investors; to understand the impediments to adoption of RI at an organisational level; to debate how financial institutions can drive the growth and adoption of RI among the investment community; and to illustrate the complexities of organisational change and the strategies that institutional entrepreneurs can use to overcome resistance to change from key stakeholders.

Case overview/synopsis:

The case is set in October 2017 against the backdrop of the pending unbundling of Old Mutual plc into four new independent businesses, and the subsequent relisting of Old Mutual Ltd on the Johannesburg Stock Exchange in South Africa. The head of responsible investment at Old Mutual Investment Group and the main protagonist of the case, Jon Duncan, is considering what the subsequent relisting will mean for the responsible investing programmes that he has set up over the past six years. The case goes on to describe how responsible investment principles were supported through the implementation of ESG integration and active ownership strategies. It also examines recent developments in ESG product innovations and demonstrates another technique available to responsible investment practitioners in the form of best-in-class ESG screening. The case ends with Duncan contemplating the strategic priorities of the RI team moving forward, and how the managed separation might impact on the RI agenda. It provides prompts for students to discuss and formulate a strategy for advancing the aims of responsible investing.

Complexity academic level

The case is aimed at postgraduate-level students enrolled in a management-related degree programme such as an MBA, and covers both sustainable and responsible finance and institutional entrepreneurship theory.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 1: Accounting and Finance
Mitchell’s Brewery: entrepreneurship challenges in the South African craft beer industry
Authors: Bick Geoff , Sidubi Fezile
Published: December 2018

Learning outcomes

They are as follows: to identify strategic growth opportunities for SMEs in the South African craft beer industry; to understand the complexities associated with operating a craft beer SME in the South African alcohol sector and analyse the SME’s strategic decision-making process that happens as a result; to understand the challenges and identify opportunities for entrepreneurship and growth in an emerging economy and niche segment; to develop a differentiation strategy for a small player in a competitive market; and to impart industry-specific knowledge and insight on the craft brewing industry.

Case overview/synopsis

The case is centred on the challenges that Hein Swart, managing director of Mitchell’s Brewery, is facing in sustaining business operations amid heavy regulations and increasing competition from existing craft breweries. In addition, there is the entry of a different type of competitor into the South African market that did not exist previously. The case narrative broadly presents several industry themes that interact with each other and create the existing complexities.

Complexity academic level

This case is targeted at postgraduate business school students with some work experience who want to build their critical thinking, business management and strategic decision-making skills such as Masters of Business Administration (MBA) and Executive MBA academic programmes, and also delegates on Executive Education programmes. The case is expected to be used as a case study for courses in entrepreneurship and strategic management; however, it can also be applied in strategic marketing courses.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 3: Entrepreneurship
Conflict handling in small firms’ foreign business relationships
Authors: Ratajczak-Mrozek Milena , Fonfara Krzysztof , Hauke-Lopes Aleksandra
Published: December 2018

Purpose

The purpose of this paper is to indicate how conflicts in foreign business relationships are handled by small firms from a relational point of view and how these conflicts can be used by small firms in a positive way.

Design/methodology/approach

The paper uses qualitative study and presents the results of in-depth interviews conducted with six small, Poland-based firms.

Findings

The paper indicates the nature of conflicts in foreign business relationships from the perspective of small firms, including the sources of conflict and its outcomes. The main sources of conflict indicated include service or product quality, financial aspects of cooperation and cultural differences. The study exposes the existence of both negative (e.g. financial consequences) and positive (e.g. gaining new experience) outcomes of conflicts. It shows that positive conflict handling often constitutes a significant challenge for small firms and that the authors cannot really speak of one optimal method of conflict handling. Regardless of the method adopted, the costs involved should be taken into detailed consideration.

Practical implications

The paper points to actions that could be taken by small firms to handle conflicts in a way that will produce positive outcomes.

Originality/value

Managing international relationships is a more challenging task compared with domestic ones, especially for smaller firms. The paper exposes the impact of two categories of conflict (called day-to-day problems and severe conflicts) in a foreign relationship on small firms and considers different methods of handling the conflict situations.
Halal tourism: state of the art
Authors: Vargas-Sánchez Alfonso , Moral-Moral María
Published: December 2018

Purpose

Halal tourism is a growing segment that represents a potentially attractive niche. However, although increasing, it is still a young and residual area of academic research. This paper aims to explore its concept, boundaries and various streams to offer a clarifying vision for researchers and tourism managers.

Design/methodology/approach

A systematization of the state of the art was carried out based on the papers contained in Web of Science and Scopus databases. Moreover, papers not indexed in these repositories (conference papers, book chapters, etc.) were searched through scientific social networks mainly.

Findings

In spite of recent efforts, halal tourism is a field of study still in a very early stage; however, on a practical level, the number of halal products and services is starting to increase worldwide. Nevertheless, there are challenges for the tourist industry in moving towards the authentication of the halal tourism offer, including among them the role of new technologies and the digital economy.

Originality/value

This paper offers a comprehensive analysis of halal tourism research. It highlights its main areas, gaps and questions for debate. In this line, a research agenda is proposed.
Phenological and fitness responses to climate warming depend upon genotype and competitive neighbourhood in Arabidopsis thaliana
Authors: Taylor Mark A. , Cooper Martha D. , Schmitt Johanna
Published: December 2018

Increasing temperatures during climate change are known to alter the phenology across diverse plant taxa, but the evolutionary outcomes of these shifts are poorly understood. Moreover, plant temperature‐sensing pathways are known to interact with competition‐sensing pathways, yet there remains little experimental evidence for how genotypes varying in temperature responsiveness react to warming in realistic competitive settings.

We compared flowering time and fitness responses to warming and competition for two near‐isogenic lines (NILs) of Arabidopsis thaliana transgressively segregating temperature‐sensitive and temperature‐insensitive alleles for major‐effect flowering time genes. We grew focal plants of each genotype in intraspecific and interspecific competition in four treatments contrasting daily temperature profiles in summer and fall under contemporary and warmed conditions. We measured phenology and fitness of focal plants to quantify plastic responses to season, temperature and competition and the dependence of these responses on flowering time genotype.

The temperature‐insensitive NIL was constitutively early flowering and less fit, except in a future‐summer climate in which its fitness was higher than the later flowering, temperature‐sensitive NIL in low competition. The late‐flowering NIL showed accelerated flowering in response to intragenotypic competition and to increased temperature in the summer but delayed flowering in the fall. However, its fitness fell with rising temperatures in both seasons, and in the fall its marginal fitness gain from decreasing competition was diminished in the future.

Functional alleles at temperature‐responsive genes were necessary for plastic responses to season, warming and competition. However, the plastic genotype was not the most fit in every experimental condition, becoming less fit than the temperature‐canalized genotype in the warm summer treatment.

Climate change is often predicted to have deleterious effects on plant populations, and our results show how increased temperatures can act through genotype‐dependent phenology to decrease fitness. Furthermore, plasticity is not necessarily adaptive in rapidly changing environments since a nonplastic genotype proved fitter than a plastic genotype in a warming climate treatment.

A plain language summary is available for this article.
Genetic and environmental contributions to the impact of a range‐expanding predator on aquatic ecosystems
Authors: Therry Lieven , Cote Julien , Cucherousset Julien , Finn Fia , Buoro Yoann , Blanchet Simon
Published: December 2018

Global change is altering biodiversity locally and globally and subsequently affecting the dynamics of communities and ecosystems. Biodiversity can be impacted both at the interspecific (i.e., species composition of communities) and at the intraspecific (evolutionary modification of phenotypic traits through selection or plasticity) levels. Changes in intraspecific diversity have been demonstrated to generate evolutionary feedbacks acting on ecological dynamics. Quantifying the role of intraspecific trait variation, global change and their interactions on ecological dynamics is of utmost importance.

Here, we used the range‐expanding dragonfly Crocothemis erythraea as a model species to test the relative effects of intraspecific trait variation in larvae and thermal conditions on the dynamics of freshwater community and ecosystem functioning. Using experimental mesocosms, we manipulated intraspecific trait variation arising from genetic (G), early developmental environment (EE) and late developmental environment (EL) contributions in a full factorial design.

We showed that intraspecific trait variation arising from genetic effects has the strongest consequences on community and ecosystem dynamics relative to trait variation driven by the thermal environment (EE and EL). Importantly, the ecological effects of trait variation due to genetic effects were partly modulated by thermal conditions (G × EL, and to a lesser extent G × EE interactions) and varied among ecological response variables. For instance, the strongest G × EL effects were observed on primary productivity and zooplankton dynamics. Trait variation driven by plasticity related to early or late developmental environments has an overall weak effect on ecological dynamics.

Intraspecific trait variation induced by genetic effects can affect ecological dynamics (evo‐to‐eco dynamics) more strongly than variation induced by the developmental environment. However, they likely interact to modulate the structure of communities and the functioning of ecosystems, highlighting the strong context (environmental) dependency of evo‐to‐eco dynamics.
Infection by invasive parasites increases susceptibility of native hosts to secondary infection via modulation of cellular immunity
Authors: Demann Felicitas , Wegner K. Mathias
Published: December 2018

Parasite spillover from invasive aliens to native species increases the risk of disease emergence within native biota—either by direct harm to the new host or by indirect effects like increased risks of secondary infection.

One example for such a detrimental effect is the parasitic copepod Mytilicola intestinalis that infected blue mussels Mytilus edulis after being introduced into the North Sea in the early 20th century. Since 1949, the parasite was blamed for multiple mass mortalities of infested blue mussels but evidence for a direct causal involvement of M. intestinalis remained circumstantial.

Here, we now examine the potential effects of primary infections by the invasive parasite on the susceptibility to secondary infections with virulent bacteria (Vibrio spp.) in a full factorial infection experiment combining parasite infection (control vs. infected) with different Vibrio infection treatments (control, bath challenge, injection) in environmental conditions that either favoured the host (ambient temperature) or the bacterium (elevated temperature). The influence of primary and secondary infections on cellular immunity (phagocytosis) and Vibrio load in the haemolymph was used to correlate these results to host survival.

Our results suggest that the rate of secondary Vibrio infection is increased due to lower efficiency of the cellular immune response. As a consequence, the failure of clearing Vibrio from the haemolymph might increase mortality of mussels infected by M. intestinalis.

This demonstrates that indirect effects of parasite invasions can outweigh direct effects of the infection highlighting the need for a more integrative approach to understand and predict the consequences of parasite invasions.
Nutritional Labelling in the EU: Strengths and Weaknesses of the Current Regulatory Framework
Authors: Cavaliere Alessia , De Marchi Elisa , Banterle Alessandro
Published: December 2018

Nutritional information on labels may impact positively on consumer food choices potentially enabling them to better judge the overall healthiness of foods and leading towards more aware and health‐oriented choices. Given its potential anticipated benefits, nutritional labelling regulation has been a priority in many countries over the last decades, and Nutrition Facts labelling became mandatory in the EU with the EU Regulation 1169/2011. However, even though mandatory Nutrition Facts labelling is crucial from a market perspective as it contributes to reducing information asymmetry, it may not be so effective from a health standpoint. Indeed, alongside mandatory indications the Regulation allows producers to report a number of additional and varying nutrition‐related information on a voluntary basis. Although these labels are important to provide consumers with supplementary contents, there is a risk that they generate information overload, making it difficult for individuals to compare different products. In this regard, consumers would likely benefit from more harmonised and standardised voluntary labels that could ultimately facilitate consumers in interpreting the nutrition facts information and translating them into a guidance for healthy food choices.
Meta synthetic biology: controlling the evolution of engineered living systems
Authors: Nørholm Morten H. H.
Published: December 2018

A major aim of synthetic biology is the design of robust living systems for real‐world applications. In seemingly contrast, evolution changes the living, exploring new survival strategies in response to environmental challenges. How do we cope with this paradox? Can we control or even exploit the molecular mechanisms of evolution for biotechnological and biosustainable innovation and will the principles of engineering lead to fundamental insights in evolutionary biology? A merger of synthetic biology with experimental evolution is occurring and it will radically accelerate the development of these scientific disciplines.
Multiple primary lung cancer versus intrapulmonary metastatic cancer: A case of multiple pulmonary nodules
Authors: Liu Chunquan , Li Huawei , Xu Kaikai , Song Shuai , He Ying , Cai Xianqi , Chu Xiangyu , Yang Jiandong , Cui Yong
Published: December 2018

A preoperative chest computed tomography examination of the right breast in a 52‐year‐old woman with breast cancer revealed multiple nodules in both lungs. The nodule in the apical segment of the upper lobe of the right lung was larger, at a diameter of approximately 2.1 cm. The patient underwent resection of the right breast, followed by thoracoscopic wedge resection of four pulmonary nodules. Hematoxylin and eosin staining and immunohistochemistry showed that the nodules in the apical and anterior segments of the upper lobe and the paravertebral nodule in the lower lobe of the right lung were primary adenocarcinoma, and the subpleural nodule in the lower lobe of the right lung was infiltrated with inflammatory cells. Exon sequencing was conducted in the resected tissue samples and blood specimens. According to the characteristics of the somatic mutations, the nodule in the apical segment of the upper lobe of the right lung was primary lung adenocarcinoma, the nodule in the anterior segment of the upper lobe and the paravertebral nodule in the lower lobe of the right lung were intrapulmonary metastatic cancer, and the subpleural nodule in the lower lobe of the right lung indicated early stage tumor progression. This case provides new evidence that conducting gene detection in multiple tissue samples from patients who have undergone resection may assist to determine the relationship among multiple nodules in the lung to exclude lung metastasis of breast cancer.
A review of accounting research in Australasia
Authors: de Villiers Charl , Hsiao Pei‐Chi Kelly
Published: December 2018

This study examines recent accounting research published in 10 journals led by New Zealand and Australia based editors, namely: Abacus; Accounting and Finance; Accounting Forum; Accounting History; Accounting, Auditing and Accountability Journal; Australian Accounting Review; International Journal of Auditing; Meditari Accountancy Research; Pacific Accounting Review; and Qualitative Research in Accounting and Management. The paper identifies the most cited recent articles (2015–2017), and the most prolific authors, universities and geographical regions. It then reveals trends in research areas and relevance of recent accounting articles. The paper discusses the importance of the Australian Business Deans Council journal quality list in facilitating novel and relevant research, and recommends the integration of citation metrics into its ratings methodology.
Data‐driven adult asthma phenotypes based on clinical characteristics are associated with asthma outcomes twenty years later
Authors: Boudier Anne , Chanoine Sébastien , Accordini Simone , Anto Josep M. , Basagaña Xavier , Bousquet Jean , Demoly Pascal , Garcia‐Aymerich Judith , Gormand Frédéric , Heinrich Joachim , Janson Christer , Künzli Nino , Matran Régis , Pison Christophe , Raherison Chantal , Sunyer Jordi , Varraso Raphaëlle , Jarvis Deborah , Leynaert Bénédicte , Pin Isabelle , Siroux Valérie
Published: December 2018

Background

Research based on cluster analyses led to the identification of particular phenotypes confirming phenotypic heterogeneity of asthma. The long‐term clinical course of asthma phenotypes defined by clustering analysis remains unknown, although it is a key aspect to underpin their clinical relevance. We aimed to estimate risk of poor asthma events between asthma clusters identified 20 years earlier.

Methods

The study relied on two cohorts of adults with asthma with 20‐year follow‐up, ECRHS (European Community Respiratory Health Survey) and EGEA (Epidemiological study on Genetics and Environment of Asthma). Regression models were used to compare asthma characteristics (current asthma, asthma exacerbations, asthma control, quality of life, and FEV1) at follow‐up and the course of FEV1 between seven cluster‐based asthma phenotypes identified 20 years earlier.

Results

The analysis included 1325 adults with ever asthma. For each asthma characteristic assessed at follow‐up, the risk for adverse outcomes differed significantly between the seven asthma clusters identified at baseline. As compared with the mildest asthma phenotype, ORs (95% CI) for asthma exacerbations varied from 0.9 (0.4 to 2.0) to 4.0 (2.0 to 7.8) and the regression estimates (95% CI) for FEV1% predicted varied from 0.6 (−3.5 to 4.6) to −9.9 (−14.2 to −5.5) between clusters. Change in FEV1 over time did not differ significantly across clusters.

Conclusion

Our findings show that the long‐term risk for poor asthma outcomes differed between comprehensive adult asthma phenotypes identified 20 years earlier, and suggest a strong tracking of asthma activity and impaired lung function over time.
“You hear voices too?”: A hearing voices group for people with learning disabilities in a community mental health setting
Authors: Roche‐Morris Aisling , Cheetham John
Published: December 2018

Accessible Summary

We ran a group for people with learning disabilities who hear voices that nobody else can hear.

During the group, people talked about what it is like to hear voices nobody else can hear and how they cope.

We interviewed people before and after the group. We asked them about what their voices say, how they felt about their voices and why they thought they heard voices. We also asked them about their quality of life and if they liked the group.

People told us that they liked the group and found it helpful to talk to other people who hear voices. Some people said they felt better after the group.

We want to run another group in the future and make it run for longer. We might run a group for family members, friends and carers.

Background

Hearing voices groups (HVGs) are effective avenues of support for people who hear voices in the general population yet their application and adaptation for people with learning disabilities who hear voices are scarce.

Methods

This paper is an evaluation of a pilot HVG for people with learning disabilities. Five people attended the group which ran once weekly for 6 weeks. Measures of psychological functioning and quality of life were collected before and after the group. Participants' understanding of their voice hearing experiences and the stigma associated with voice hearing were explored at the pre‐ and post‐group stage.

Results

High attendance rates and positive satisfaction ratings suggested the group was acceptable to clients. Participants said they had increased understanding of voice hearing and endorsed the positive value of social support.

Conclusions

The use of quantitative outcome measures should be reviewed when conducting HVGs. Although the 6‐week group was associated with positive feedback, there might be benefit in extending the number of sessions offered as well as involving carers. Bridging the gap between services available for those who hear voices in the general population compared to people with a learning disability is essential.
Glacio‐isostatic age modelling and Late Weichselian deglaciation of the Lögurinn basin, East Iceland
Authors: Norðdahl Hreggviður , Ingólfsson Ólafur , Vogler Erla D. , Steingrímsson Benedikt Ó. , Hjartarson Árni
Published: December 2018

Knowledge of the glaciation of central East Iceland between 15 and 9 cal. ka BP is important for the understanding of the extent, retreat and dynamics of the Icelandic Ice Sheet. Crucially, it is not known if the key area of Fljótsdalur‐Úthérað carried a fast‐flowing ice stream during the Last Glacial Maximum; the timing and mode of deglaciation is unclear; and the history and ages of successive lake‐phases in the Lögurinn basin are uncertain. We use the distribution of glacial and fluvioglacial deposits and gradients of former lake shorelines to reconstruct the glaciation and deglaciation history, and to constrain glacio‐isostatic age modelling. We conclude that during the Last Glacial Maximum, Fljótsdalur‐Úthérað was covered by a fast‐flowing ice stream, and that the Lögurinn basin was deglaciated between 14.7 and 13.2 cal. ka BP at the earliest. The Fljótsdalur outlet glacier re‐advanced and reached a temporary maximum extent on two separate occasions, during the Younger Dryas and the Preboreal. In the Younger Dryas, about 12.1 cal. ka BP, the outlet glacier reached the Tjarnarland terminal zone, and filled the Lögurinn basin. During deglaciation, a proglacial lake formed in the Lögurinn basin. Through time, gradients of ice‐lake shorelines increased as a result of continuous but non‐uniform glacio‐isostatic uplift as the Fljótsdalur outlet glacier retreated across the Valþjófsstaður terminal zone. Changes in shoreline gradients are defined as a function of time, expressed with an exponential equation that is used to model ages of individual shorelines. A glaciolacustrine phase of Lake Lögurinn existed between 12.1 and 9.1 cal. ka BP; as the ice retreated from the basin catchment, a wholly lacustrine phase of Lake Lögurinn commenced and lasted until about 4.2 cal. ka BP when neoglacial ice expansion started the current glaciolacustrine phase of the lake.
Optimizing the clinical utility of sirolimus‐based immunosuppression for kidney transplantation
Authors: Tedesco‐Silva Helio , del Carmen Rial Maria , Cruz Santiago Jose , Mazzali Marilda , Pacheco‐Silva Alvaro , Torres Rodolfo
Published: December 2018

While calcineurin inhibitors (CNIs) are effective for preventing acute rejection in kidney transplant recipients, long‐term use may cause chronic kidney injury and is associated with increased risks of cardiovascular events, cancer, and infection‐associated death. Immunosuppression strategies are needed to balance risks of acute and subclinical rejection with long‐term benefits of improved kidney function. Sirolimus, an inhibitor of mammalian target of rapamycin, is used for immunosuppression in kidney transplantation. Its clinical utility has evolved, over more than 15 years, including de novo sirolimus with and without concomitant CNIs and conversion from CNI‐based regimens to sirolimus. Sirolimus‐containing regimens are associated with preservation of good renal function, with promising characteristics for improving long‐term graft and patient survival, including antiviral and anticancer effects. Based on clinical evidence, use of low‐dose sirolimus in a de novo approach with tacrolimus/steroids in the immediate posttransplantation period is appropriate. A feasible alternative is a long term, CNI‐free combination with mycophenolate mofetil (following CNI‐to‐sirolimus conversion at 3‐6 months). These strategies are appropriate for a broad range of patients with various levels of immunologic risk, including those receiving expanded criteria donor kidneys or at increased risk of delayed graft function, particular challenges in Latin America and other global regions.
Metabolic rhythms: A framework for coordinating cellular function
Authors: Causton Helen C.
Published: December 2018

Circadian clocks are widespread among eukaryotes and generally involve feedback loops coupled with metabolic processes and redox balance. The organising power of these oscillations has not only allowed organisms to anticipate day–night cycles, but also acts to temporally compartmentalise otherwise incompatible processes, enhance metabolic efficiency, make the system more robust to noise and propagate signals among cells. While daily rhythms and the function of the circadian transcription‐translation loop have been the subject of extensive research over the past four decades, cycles of shorter period and respiratory oscillations, with which they are intertwined, have received less attention. Here, we describe features of yeast respiratory oscillations, which share many features with daily and 12 hr cellular oscillations in animal cells. This relatively simple system enables the analysis of dynamic rhythmic changes in metabolism, independent of cellular oscillations that are a product of the circadian transcription‐translation feedback loop. Knowledge gained from studying ultradian oscillations in yeast will lead to a better understanding of the basic mechanistic principles and evolutionary origins of oscillatory behaviour among eukaryotes.
Modelling inducible defences in predator–prey interactions: assumptions and dynamical consequences of three distinct approaches
Authors: Yamamichi Masato , Klauschies Toni , Miner Brooks E. , van Velzen Ellen
Published: December 2018

Inducible defences against predation are widespread in the natural world, allowing prey to economise on the costs of defence when predation risk varies over time or is spatially structured. Through interspecific interactions, inducible defences have major impacts on ecological dynamics, particularly predator–prey stability and phase lag. Researchers have developed multiple distinct approaches, each reflecting assumptions appropriate for particular ecological communities. Yet, the impact of inducible defences on ecological dynamics can be highly sensitive to the modelling approach used, making the choice of model a critical decision that affects interpretation of the dynamical consequences of inducible defences. Here, we review three existing approaches to modelling inducible defences: Switching Function, Fitness Gradient and Optimal Trait. We assess when and how the dynamical outcomes of these approaches differ from each other, from classic predator–prey dynamics and from commonly observed eco‐evolutionary dynamics with evolving, but non‐inducible, prey defences. We point out that the Switching Function models tend to stabilise population dynamics, and the Fitness Gradient models should be carefully used, as the difference with evolutionary dynamics is important. We discuss advantages of each approach for applications to ecological systems with particular features, with the goal of providing guidelines for future researchers to build on.
BDNF+/− rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders
Authors: Martis Lena‐Sophie , Wiborg Ove , Holmes Megan C. , Harris Anjanette P.
Published: December 2018

Major depressive disorder (MDD) is a leading contributor to the global burden of disease. However, the causal relationship of risk factors, such as genetic predisposition or experience of augmented stress, remain unknown. Numerous studies in humans and rodents have implicated brain‐derived neurotrophic factor (BDNF) in MDD pathology, as a genetic risk factor and a factor regulated by stress. Until now, the majority of preclinical studies have employed genetically modified mice as their model of choice. However, mice display a limited behavioural repertoire and lack expression of circulating BDNF, which is present in rats and humans. Therefore, heterozygous BDNF (BDNF+/−) rats were tested for affective behaviours and accompanying expression of key genes associated with affective disorders in the brain. We found that BDNF+/− rats, which have reduced BDNF levels in brain and plasma, displayed symptoms of anhedonia, a core symptom of MDD, and anxiety‐like behaviour, but no behavioural despair or cognitive impairments. This was accompanied by changes in the expression of genes that are implicated in modulation of the stress response and affective disorders. Hence, glucocorticoid receptor, neuregulin 1 and disrupted‐in‐schizophrenia 1 gene expression were upregulated in the prefrontal cortex of BDFN+/− rats, whereas FK506 binding protein 5 levels were decreased in the hippocampus. We conclude that a reduction in BDNF levels alters expression of genes associated with affective disorders, which may contribute to the development of depressive‐like symptoms.
Effect of specimen geometry on kinetics of thermal decomposition of minerals in porous ceramic tiles
Authors: Cargnin Maykon , Kammer Eduardo H. , Ulson de Souza Antônio A. , De Noni Jr Agenor , Ulson de Souza Selene M. A. G.
Published: December 2018

Porous ceramic tiles are used as covering for indoor vertical surfaces in buildings. Clay and limestone are the starting raw materials. The firing step consolidates the product's properties in the manufacturing process. In this step several reactions occur, among them are the dehydroxylation of the clay minerals and decomposition of the carbonates. This study determined the kinetics parameters associated with the decomposition of these 2 minerals. Two different methods of samples preparation were investigated. In the first method, 60 mg of a spray‐dried powder was submitted to analysis in traditional thermogravimetric equipment. In the second method, compacted specimens with dimensions of 80 × 20 × 2.5 mm³ and a mass of 7 g, compacted at 25 MPa, were submitted to analysis using customized thermogravimetric apparatus. The curves were obtained for 6 different heating rates between 2.5 and 20 K min−1. The activation energy, the pre‐exponential factor of the specific velocity equation, and the reaction mechanism were determined. Depending on the methods and compaction degree the activation energy varies from 177.0 to 224.7 kJ mol−1 and from 188.5 to 230.2 kJ mol−1 for kaolinite and calcium carbonate, respectively. For accurate measurement of the activation energy, the heat transfer needs to be considered for each particular experimental configuration.
Structural and optical properties of doped ZnO/SiO2 nanocomposite
Authors: Mohamed Mohamed Bakr , Abdel‐Kader Mohamed H. , Alhazime Ali A.
Published: December 2018

The synthesis of ZnO/SiO2 nanocomposite doped with Co, Cu and Mn nanoparticles were performed using sol‐gel method. Rietveld refinement analysis was done for the X‐ray diffraction data and results showed that all samples are single wurtzite hexagonal phase and have an average crystallite size ~14 nm. The lattice parameters, bond length, crystallite size, microstrain, dislocation density and the system volume were studied in details. Transmission electron microscopy technique showed that nanoparticles characterized by an elliptical shape. Fourier transform infrared and scanning electron microscope techniques proved the presence of SiO2 in the system. The energy gap values of both undoped and doped samples with Co, Mn and Cu were 2.84, 2.47, 2.71 and 2.8 eV, respectively. Photoluminescence spectra for undoped and doped ZnO/SiO2 were investigated in details.
Real business cycles, animal spirits, and stock market valuation
Authors: Lansing Kevin J.
Published: December 2018

This paper develops a real business cycle model with five types of fundamental shocks and one “equity sentiment shock” that captures fluctuations driven by animal spirits. The representative agent's perception that movements in equity value are partly driven by sentiment turns out to be close to self‐fulfilling. I solve for the sequences of shock realizations that allow the model to exactly replicate the observed time paths of US consumption, investment, hours worked, the stock of physical capital, capital's share of income, and the S&P 500 market value from 1960.Q1 onwards. The model‐identified sentiment shock is strongly correlated with survey‐based measures of US consumer sentiment. Counterfactual scenarios with the model suggest that the equity sentiment shock has an important influence on the paths of most US macroeconomic variables.
International credit markets and global business cycles
Authors: Pintus Patrick A. , Wen Yi , Xing Xiaochuan
Published: December 2018

This paper stresses a new channel through which global financial linkages contribute to the co‐movement in economic activity across countries. We show in a two‐country setting with borrowing constraints that international credit markets are subject to self‐fulfilling variations in the world real interest rate. Those expectation‐driven changes in the borrowing cost in turn act as global shocks that induce strong cross‐country co‐movements in both financial and real variables (such as asset prices, gross domestic product, consumption, investment, and employment). When firms around the world benefit from unexpectedly low debt repayments, they borrow and invest more, which leads to excessive supply of collateral and of loanable funds at a low interest rate, thus fueling a boom both at home and abroad. As a consequence, business cycles are synchronized internationally. Such a stylized model thus offers one way to rationalize both the existence of a world business‐cycle component, documented by recent empirical studies through dynamic factor analysis, and the factor's intimate link to global financial markets.
Long‐term safety and efficacy of antimuscarinic add‐on therapy in patients with overactive bladder who had a suboptimal response to mirabegron monotherapy: A multicenter, randomized study in Japan (MILAI II study)
Authors: Yamaguchi Osamu , Kakizaki Hidehiro , Homma Yukio , Igawa Yasuhiko , Takeda Masayuki , Nishizawa Osamu , Gotoh Momokazu , Yoshida Masaki , Yokoyama Osamu , Seki Narihito , Okitsu Akira , Hamada Takuya , Kobayashi Akiko , Kuroishi Kentaro
Published: December 2018

Objectives

To evaluate the long‐term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add‐on therapy in patients receiving mirabegron.

Methods

During a 2‐week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks’ treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment‐emergent adverse events, vital signs, 12‐lead electrocardiograms, post‐void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night‐time micturitions.

Results

Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment‐emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores.

Conclusions

Antimuscarinic add‐on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.
Large strain under low driving field in lead‐free relaxor/ferroelectric composite ceramics
Authors: Fan Pengyuan , Zhang Yangyang , Zhu Yiwei , Ma Weigang , Liu Kai , He Xueting , Marwat Mohsin Ali , Xie Bing , Li Ming , Zhang Haibo
Published: December 2018

0.75(Na0.5Bi0.5)TiO3–0.25SrTiO3 lead‐free incipient piezoceramic is a promising candidate for actuator applications due to their large reversible electromechanical strains at the relatively low driving field of 40 kV/cm. In order to further reduce the driving field of 0.75(Na0.5Bi0.5)TiO–0.25SrTiO3 relaxor ceramic to meet the requirements for real actuators application, the relaxor/ferroelectric (RE/FE) 0‐3 composite ceramics method was employed. The polarization and strain behaviors were examined as a function of the weight ratio of the relaxor/ferroelectric phases. It was found that 90 wt% 0.75(Na0.5Bi0.5)TiO3–0.25SrTiO3/10 wt% 0.96(Na0.84K0.16)1/2Bi1/2TiO3–0.04SrTiO3 RE/FE 0‐3 type composite samples provided a high unipolar strain of 0.25% and the corresponding large‐signal piezoelectric coefficient, d*33 of 833 pm/V at 30 kV/cm, which are 32% higher than the values of the pure 0.75(Na0.5Bi0.5)TiO3–0.25SrTiO3. The enhanced electric‐field‐induced strain at relatively lower field was attributed primarily to the reduction in the RE‐FE phase transition electric field. It was also found that the RE/FE composite ceramics exhibited significantly reduced frequency dependence in the unipolar strain behavior at room temperature.
Cell‐based high‐throughput screen for small molecule inhibitors of Bax translocation
Authors: Hui Kelvin Kai‐Wan , Dojo Soeandy Chesarahmia , Chang Stephano , Vizeacoumar Frederick S. , Sun Thomas , Datti Alessandro , Henderson Jeffrey T.
Published: December 2018

Aberrant regulation of programmed cell death (PCD) has been tied to an array of human pathologies ranging from cancers to autoimmune disorders to diverse forms of neurodegeneration. Pharmacologic modulation of PCD signalling is therefore of central interest to a number of clinical and biomedical applications. A key component of PCD signalling involves the modulation of pro‐ and anti‐apoptotic Bcl‐2 family members. Among these, Bax translocation represents a critical regulatory phase in PCD. In the present study, we have employed a high‐content high‐throughput screen to identify small molecules which inhibit the cellular process of Bax re‐distribution to the mitochondria following commitment of the cell to die. Screening of 6246 Generally Recognized As Safe compounds from four chemical libraries post‐induction of cisplatin‐mediated PCD resulted in the identification of 18 compounds which significantly reduced levels of Bax translocation. Further examination revealed protective effects via reduction of executioner caspase activity and enhanced mitochondrial function. Consistent with their effects on Bax translocation, these compounds exhibited significant rescue against in vitro and in vivo cisplatin‐induced apoptosis. Altogether, our findings identify a new set of clinically useful small molecules PCD inhibitors and highlight the role which cAMP plays in regulating Bax‐mediated PCD.