bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Upconverting nanoparticles towards heart theranostics
Authors: Marc Kermorgant , Jennifer Ben Salem , Julien Santelli , Denis Calise , Anne-Cécile Oster , Olivier Lairez , Christophe Coudret , Marc Verelst , Céline Gales , Jean-Michel Senard , Francis Beaudry , Anne Pavy-Le Traon , Clément Roux , Robert Mauricot , Arvanitis Dina N. 
Published: August 2019

AbstractRestricted and controlled drug delivery to the heart remains a challenge giving frequent off-target effects as well as limited retention of drugs in the heart. There is a need to develop and optimize tools to allow for improved design of drug candidates for treatment of heart diseases. Over the last decade, novel drug platforms and nanomaterials were designed to confine bioactive materials to the heart. Yet, the research remains in its infancy, not only in the development of tools but also in the understanding of effects of these materials on cardiac function and tissue integrity. Upconverting nanoparticles are nanomaterials that recently accelerated interest in theranostic nanomedicine technologies. Their unique photophysical properties allow for sensitive in vivo imaging that can be combined with spatio-temporal control for targeted release of encapsulated drugs.Here we synthesized upconverting NaYF4:Yb,Tm nanoparticles and show for the first time their innocuity in the heart, when injected in the myocardium or in the pericardial space in mice. Nanoparticle retention and upconversion in the cardiac region did not alter heart rate variability, nor cardiac function as determined over a 15-day time course ensuing the sole injection. Altogether, our nanoparticles show innocuity primarily in the pericardial region and can be safely used for controlled spatiotemporal drug delivery.Our results support the use of upconverting nanoparticles as potential theranostics tools overcoming some of the key limitations associated with conventional experimental cardiology.
LRRK2 G2019S kinase activity triggers neurotoxic NSF aggregation
Authors: Pischedda Francesca , Cirnaru Maria Daniela , Ponzoni Luisa , Sandre Michele , Biosa Alice , Carrion Maria Perez , Marin Oriano , Morari Michele , Pan Lifeng , Greggio Elisa , Bandopadhyay Rina , Sala Mariaelvina , Piccoli Giovanni 
Published: August 2019

SummaryParkinson’s disease (PD) is characterized by the progressive degeneration of dopaminergic neurons within the substantia nigra pars compacta and the presence of protein aggregates in surviving neurons. LRRK2 G2019S mutation is one of the major determinants of familial PD cases and leads to late-onset PD with pleomorphic pathology, including alpha-synuclein accumulation and deposition of protein inclusions. We demonstrated that LRRK2 phosphorylates N-ethylmaleimide sensitive factor (NSF). We observed aggregates containing NSF in basal ganglia specimens from G2019S carrier PD patients and in cellular and animal models expressing the LRRK2 G2019S variant. We found that LRRK2 G2019S kinase activity induces the accumulation of NSF in toxic aggregates. Noteworthy, the induction of autophagy cleared NSF aggregation and rescued motor and cognitive impairment observed in aged hG2019S BAC mice. We suggest that LRRK2 G2019S pathological phosphorylation hampers substrate catabolism, thus causing the formation of cytotoxic protein inclusions.HighlightsLRRK2 phosphorylates NSF in vivoNSF aggregates in complementary LRRK2 G2019S modelsLRRK2 G2019S kinase activity induces NSF accumulation in toxic aggregatesAutophagy induction rescues hG2019S BAC mice motor and cognitive impairment
VIP-producing enteric neurons interact with innate lymphoid cells to regulate feeding-dependent intestinal epithelial barrier functions
Authors: Talbot Jhimmy , Hahn Paul , Kroehling Lina , Nguyen Henry , Li Dayi , Littman Dan R. 
Published: August 2019

ABSTRACTThe intestinal mucosa serves as both a conduit for uptake of food-derived nutrients and microbiome-derived metabolites and as a barrier that prevents tissue invasion by microbes and tempers inflammatory responses to the myriad contents of the lumen. How the intestine coordinates physiological and immune responses to food consumption to optimize nutrient uptake while maintaining barrier functions remains unclear. Here, we describe how a gut neuronal signal triggered by food intake is integrated with intestinal antimicrobial and metabolic responses controlled by type 3 innate lymphoid cells (ILC3)1-3. Food consumption rapidly activates a population of enteric neurons that express vasoactive intestinal peptide (VIP)4. Projections of VIP-producing neurons (VIPergic neurons) in the lamina propria are in close proximity to clusters of ILC3 that selectively express VIP receptor type 2 (VIPR2 or VPAC2). ILC3 production of IL-22, which is up-regulated by commensal microbes such as segmented filamentous bacteria (SFB)5-7, is inhibited upon engagement of VIPR2. As a consequence, there is a reduction in epithelial cell-derived antimicrobial peptide, but enhanced expression of lipid-binding proteins and transporters8. During food consumption, activation of VIPergic neurons thus enhances growth of epithelial-associated SFB and increases lipid absorption. Our results reveal a feeding- and circadian-regulated dynamic intestinal neuro-immune circuit that promotes a trade-off between IL-22-mediated innate immune protection and efficiency of nutrient absorption. Modulation of this pathway may hence be effective for enhancing resistance to enteropathogen2,3,9 and for treatment of metabolic diseases.
Mutations of R882 in DNMT3A change flanking sequence preferences and cellular methylation patterns in AML
Authors: Emperle Max , Adam Sabrina , Kunert Stefan , Dukatz Michael , Baude Annika , Plass Christoph , Rathert Philipp , Bashtrykov Pavel , Jeltsch Albert 
Published: August 2019

AbstractDNMT3A R882 mutations are frequently observed in AML including the abundant R882H and the rare R882C, R882P and R882S. Using deep enzymology we show here that the DNMT3A-R882H has more than 70-fold altered flanking sequence preferences when compared with wildtype DNMT3A. The R882H flanking sequence preferences mainly differ on the 3’ side of the CpG site, where they resemble DNMT3B, while 5’ flanking sequence preferences of R882H resemble wildtype DNMT3A, indicating that R882H behaves like a DNMT3A/DNMT3B chimera. Activities and flanking sequence preferences of R882C, R882P and R882S were determined as well. Genomic methylation patterns after expression of wildtype DNMT3A and R882H in human cells reflect the flanking sequence preferences. R882H specific hypermethylation in AML patients are correlated with R882H flanking sequence preferences. The hypermethylation events are accompanied by R882H specific misregulation of several genes with strong cancer connection in AML patients, which are potential downstream targets of R882H.
Immune Regulation of Intestinal Stem Cell Proliferation and Differentiation in Drosophila
Authors: Shin Minjeong , Ferguson Meghan , Willms Reegan J. , Jones Lena O. , Petkau Kristina , Foley Edan 
Published: August 2019

ABSTRACTIntestinal progenitor cells integrate signals from their niche, and from the gut lumen, to divide and differentiate at a rate that maintains an epithelial barrier to microbial invasion of the host interior. Despite the importance of evolutionarily conserved innate immune defenses to maintain stable host-microbiota relationships, we know little about specific contributions of stem cell immunity to gut homeostasis. We used the Drosophila model to determine the consequences of compromised intestinal stem cell immune activity for epithelial homeostasis. We showed that loss of stem cell immunity greatly impacted growth and renewal in the adult gut. In particular, we noticed that inhibition of stem cell immunity impeded key growth and differentiation events in the progenitor cell compartment leading to a gradual loss of stem cell numbers with age, and an impaired differentiation of mature enteroendocrine cells. Our results highlight the importance of immune signaling in the stem cell population for epithelial function in the adult gut.HIGHLIGHTSThe TNFR-like Immune Deficiency (IMD) pathway is active in Drosophila intestinal progenitor cells.Inhibition of IMD in progenitors impairs progenitor cell proliferation.Blocking progenitor cell IMD negatively affects generation of mature epithelial cells.
Large-scale examination of neuropsychiatric, cognitive and cardiovascular phenotypic associations with 15q11.2 BP1-BP2 deletion in ∼500,000 UK Biobank individuals
Authors: Williams Simon G. , Nakev Apostol , Guo Hui , Frain Simon , Tenin Gennadiy , Liakhovitskaia Anna , Saha Priyanka , Priest James R. , Hentges Kathryn E. , Keavney Bernard D. 
Published: August 2019

AbstractBackgroundDeletion of a non-imprinted 500Kb genomic region at chromosome 15q11.2, between breakpoints 1 and 2 of the Prader-Willi/Angelman locus (BP1-BP2 deletion) has been associated in previous studies with phenotypes including developmental delay, autism, schizophrenia and congenital cardiovascular malformations (CVM). The deletion has a low baseline population prevalence and large-scale data regarding the magnitude of these associations and any milder effects on cognition phenotypes, in populations not selected for disease, are limited.MethodsUsing the UK Biobank (UKB) cohort of ∼500,000 individuals, we identified individuals with neuropsychiatric and CVM diagnoses and investigated their association with deletions at the BP1-BP2 locus. In addition we assessed the association of BP1-BP2 deletions with cognitive function and academic achievement in individuals with no previous diagnosis.ResultsCases of neurodevelopmental and CVM disease had an increased prevalence of the deletion compared to controls (0.68%; OR=1.84 [95% CI 1.23 – 2.75]; p=0.004 and 0.64%; OR=1.73 [95% CI 1.08 – 2.75]; p=0.03 respectively). Excluding participants diagnosed with neurodevelopmental or neuropsychiatric disease, deletion carriers had worse scores in four tests of cognitive function, and while 32.8% of UKB participants without BP1-BP2 deletion had a university or college degree as their highest educational qualification, only 22.8% of deletion carriers achieved this (OR 0.57 [95% CI 0.51-0.64]; p=5.60E-22).ConclusionsWe conclude that BP1-BP2 deletion has an appreciable population prevalence with important life-course impacts on undiagnosed carriers. These data are of potential utility in deciding the circumstances under which clinical testing for BP1-BP2 deletion may be helpful.Key messagesDeletions at chromosome 15q11.2 between breakpoints 1 and 2 (BP1-BP2), which encompass four genes, have been associated with developmental delay, autism, schizophrenia and congenital cardiovascular malformations.Here, we use the largest cohort studied to date: the UK Biobank cohort of ∼500,000 individuals, to explore the association of this deletion with neuropsychiatric and cardiovascular phenotypes as well as its effects on cognitive function and academic achievement.We find an appreciable population prevalence of the deletion with these phenotypes and demonstrate reduced cognitive function and lower academic achievements in those individuals with no prior diagnosis.
Buying on rumors: how financial news flows affect the share price of Tesla
Authors: Strauss Nadine , Smith Christopher Holmes 
Published: August 2019

PurposeThe purpose of this paper is to research how corporate communication regarding a specific corporate event (i.e. Tesla’s tweets about a new product) as well as the framing of both the event itself and the market reactions therewith in the news media influence the formation of the share price of the respective company over time. In so doing, the study provides insights into the nature of market-moving information and the role of financial news flows in shaping market reactions in today’s high-frequency news and information environment.Design/methodology/approachUsing a multi-method case study approach, combining quantitative intraday event studies with a qualitative text analysis of financial online news and tweets by Elon Musk and Twitter, the authors shed light on the complex interaction between market events, financial information and stock market reactions. The analysis covers a period of four days, encompassing the announcement and introduction of the new battery pack for Model S and X by Tesla as well as the accompanying and follow-up reporting by the financial news media.FindingsFindings show that market reactions are driven by business events and expectations among the market rather than the follow-up reporting by financial news media. Financial online news instead seems to heavily rely on Elon Musk’s attention-triggering news to sustain its 24-h airtime with a variety of reporting tools, keeping the highly demanded audience engaged. Eventually, Twitter accounts of media visible companies and personalities, such as Tesla and its CEO Elon Musk, have been found to be useful market information sources for day traders and shareholders to trade at a profit.Originality/valueThe study is a response to recent discussions about the legitimacy of Twitter communication by CEOs or representatives of listed companies. The findings show that Twitter communication needs to be well considered in light of strict market regulations (e.g. SEC in the USA) regarding insider-trading and the publication of market-relevant information. In addition, corporate financial communication should avoid impetuous communication via social media channels as this could have deterrent effects on the market valuation of a listed company.
No end in sight: the international drug control system once again baulks at the prospect of reform
Authors: Axel Klein , Stothard Blaine 
Published: August 2019

Purpose
In two separate sections the authors summarise the observations, use the insights to reflect on some of the propositions made in the book, and follow the appeal of one of the authors to civil society and academics to “help governments out of the drug policy dilemma that is now facing them”. The paper aims to discuss this issue.

Design/methodology/approach
The genre the authors follow here is ethnography and the material takes the form of reflective field notes. Since each author follows a particular set of interests the authors split the paper into two sections. There are no strong conclusions, safe that the concerns about the international drug control system were fully borne out by events on the floor.

Findings
The role of CSOs is critical in moving the process forward – but countries are likely to drift apart as the policy differences are becoming inrreconcilable.

Research limitations/implications
It is imperative to develop new models of cooperation in the management of psychactive substances.

Practical implications
This is in recognition that at national level just as much as at Commission on Narcotic Drugs (CND) and UN General Assembly Special Session the increased involvement of CSOs has been pivotal in shifting focus towards public health and human rights. This in turn has encouraged some nations to do the same in their domestic policies – and to stand up and say so in CND meetings.

Social implications
More involvement of academics and editorial teams in the design of sustainable policies and practices.

Originality/value
In a critical report on the CND the authors challenge the viability of the international drug control regime in view of the emerging differences between different member states. This is the first attempt in the drug policy literature to assess the durability of the drug control regime as it is faced by the fast paced transformation of cannabis into a recognised medicine and regulated recreational substance. If the appearance of agreement is maintained this is entirely for diplomatic reasons and organisational benefit. In reality, the system is breaking apart and new methods for regulating drugs are emerging.
Smart campus tools 2.0 exploring the use of real-time space use measurement at universities and organizations
Authors: Valks Bart , Arkesteijn Monique , Den Heijer Alexandra 
Published: August 2019

Purpose
The purpose of this study is to generate knowledge about the use of smart campus tools to improve the effective and efficient use of campuses. Many universities are facing a challenge in attuning their accommodation to organisational demand. How can universities invest their resources as effectively as possible and not in space that will be poorly utilized? The hypothesis of this paper is that by using smart campus tools, this problem can be solved.

Design/methodology/approach
To answer the research question, previous survey at 13 Dutch universities was updated and compared with a survey of various universities and other organizations. The survey consisted of interviews with structured and semi-structured questions, which resulted in a unified output for 27 cases.

Findings
Based on the output of the cases, the development of smart campus tools at Dutch universities was compared to that of international universities and other organizations. Furthermore, the data collection led to insights regarding the reasons for initiating smart campus tools, user and management information, costs and benefits and foreseen developments.

Originality/value
Although the use of smart tools in practice has gained significant momentum in the past few years, research on the subject is still very technology-oriented and not well-connected to facility management and real estate management. This paper provides an overview of the ways in which universities and organizations are currently supporting their users, improving the use of their buildings and reducing their energy footprint through the use of smart tools.
Application of conjoint analysis to the optimum design for fabric printing patterns
Authors: Lin Chiahsu , Wang Ya-Ching 
Published: August 2019

Purpose
The purpose of this paper is to construct the best combination of fabric printing pattern’s attributes to obtain the optimum design to meet the markets need.

Design/methodology/approach
This study reviewed the morphological analysis of fashion design expert groups regarding the fashionable fabric printing patterns, as well as the attribute preferences for different groups of fabric printing patterns through focus group discussions. In addition, the conjoint analysis was used to calculate the part-worth of these patterns’ design attributes and design levels to obtain the optimum design for fabric printing patterns.

Findings
The results of this study showed that the most importance of fabric attributes is the secondary pattern (32.59 percent), while the weights of shading element (24.80 percent) and primary pattern (24.46 percent) are almost the same. This study found that a wide range of intertwining image primary pattern can be applied to create interesting and popular fabric printing pattern designs. In practical applications of this result, when the primary pattern is supported by the buyer, fabric designers may use New Classic composite plants, with simple shading and different cycling configuration, to reproduce the optimum designs of the fabric printing patterns.

Originality/value
This proposed a novel solution to figure out the combination basis for optimizing fabric printing pattern designs. In addition, this result helps fabric printing pattern designers to establish an optimal design method for a specific brand to create a unique printing pattern design.
Interdependence and contagion in the period of crisis
Authors: Santos Carolina Macagnani dos , Gaio Luiz Eduardo , Pimenta Junior Tabajara , Cicconi Eduardo Garbes 
Published: August 2019

Purpose
The purpose of this paper is to investigate whether the relationship of interdependence and contagion between BRICS countries and emerging non-BRICS countries is similar to that observed between developed countries and emerging BRICS countries.

Design/methodology/approach
The authors analyzed 15 markets: 5 BRICS, 5 developed (USA, Japan, Germany, England and France) and 5 emerging markets (Mexico, Indonesia, Turkey, Iran and Poland). Based on the time series of returns of the main stock indexes of each country, referring to the period from 2008 to 2018, the authors applied Granger causality tests, vector auto-regression and the dynamic conditional correlation-GARCH model.

Findings
The results led to the rejection of the main hypothesis and showed adherence to the behaviors predicted in the literature for the relations between the groups of markets.

Originality/value
This paper, besides analyzing the interdependence between markets in times of crisis, analyzes the effect of contagion between developed and emerging markets.
An alternative approach to safety integrity level determination: results from a case study
Authors: Ouazraoui Nouara , Nait-Said Rachid 
Published: August 2019

Purpose
The purpose of this paper is to validate a fuzzy risk graph model through a case study results carried out on a safety instrumented system (SIS).

Design/methodology/approach
The proposed model is based on an inference fuzzy system and deals with uncertainty data used as inputs of the conventional risk graph method. The coherence and redundancy of the developed fuzzy rules base are first verified in the case study. A new fuzzy model is suggested for a multi-criteria characterization of the avoidance possibility parameter. The fuzzy safety integrity level (SIL) is determined for two potential accident scenarios.

Findings
The applicability of the proposed fuzzy model on SIS shows the importance and pertinence of the proposed fuzzy model as decision-making tools in preventing industrial hazards while taking into consideration uncertain aspects of the data used on the conventional risk graph method. The obtained results show that the use of continuous fuzzy scales solves the problem of interpreting results and provides a more flexible structure to combine risk graph parameters. Therefore, a decision is taken on the basis of precise integrity level values and protective actions in the real world are suggested.

Originality/value
Fuzzy logic-based safety integrity assessment allows assessment of the SIL in a more realistic way by using the notion of the linguistic variable for representing information that is qualitative and imprecise and, therefore, ensures better decision making on risk prevention.
BIM-based facilities information: streamlining the information exchange process
Authors: Matarneh Sandra , Danso-Amoako Mark , Al-Bizri Salam , Gaterell Mark , Matarneh Rana 
Published: August 2019

Purpose
The purpose of this study is to address challenges in the current information exchange process between building information modelling (BIM) and facilities management (FM) systems and to propose a workable solution. This study’s objective is to identify the information exchange requirements and to develop methods for seamless information flow between building information models and FM systems.

Design/methodology/approach
Data collection and analysis was based on an extensive literature review of similar studies followed by a questionnaire survey with a total of 112 participants and 2 focus groups with a total of 12 participants to validate the conceptual framework. The outputs of the survey analysis formed the background of the proposed framework to streamline information exchange process between building information models and FM systems.

Findings
The study findings form a foundation for enabling the integration of various data sources including building information models. Such integrated platforms will enable automated information exchange between the various data sources and FM systems. The study also provides key information requirements sources to complement the existing construction operations building information exchange information and to support standardization for information exchange process.

Originality/value
The contribution of this study is the identification of information exchange requirements and sources to enable seamless information flow between BIM and FM systems. The study findings will also lay the basis for research studies using the developed framework context to enable the identification of specific data outputs for FM systems inputs.