bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Precautionary Principle: Its Use Within Hard and Soft Law
Authors: von Schomberg René 
Published: February 2017

The precautionary principle in public decision making concerns situations where following an assessment of the available scientific information, there are reasonable grounds for concern for the possibility of adverse effects on the environment or human health, but scientific uncertainty persists. In such cases provisional risk management measures may be adopted, without having to wait until the reality and seriousness of those adverse effects become fully apparent. This is the definition of the precautionary principle as operationalized under EU law. The precautionary principle is a deliberative principle. Its application involves deliberation on a range of normative dimensions which need to be taken into account while making the principle operational in the public policy context. Under EU law, any risk management measures to be adopted while implementing the precautionary principle, have to be proportionate to ensure the chosen high level of protection in the European Community.This article will illustrate the established practice concerning the release of genetically modified organisms into the environment and how the principle is implemented under hard law. The article also provides an outlook on what this may imply for the relative new case of nanotechnology and the use of precautionary principle within the context of soft law (use of codes of conduct).
Framing Risk Regulation : A Critical Reflection
Authors: Fisher Elizabeth 
Published: February 2017

Over a decade ago I was involved in a group project that focused on developing a regulatory model concerning the implementation of the precautionary principle in the EU. The project involved a number of workshops and in those workshops I used to joke about the fact that while there were many different frameworks being produced to represent risk regulation, these diagrams basically fell into two different categories. In the first category there were those diagrams that characterised risk regulation as a linear process involving usually a scientific process of risk assessment and then political processes of risk management and risk communication. In the second category there were those diagrams that had lots of looping arrows going all over the place that represented the fact that risk regulation was an iterative process that constantly involved many scientific, socio-political and other inputs.Behind my joking was a sense of hope. The linear diagrams did have their minimalist appeal, but the messy diagrams captured much of the reality of this area of regulatory practice.
Divergences between EU and US in the Financial Regulation
Authors: Pugliese Sara 
Published: February 2017

Financial regulation is an issue where differences between the EU and US are highly sensitive. Indeed, EU and US apply in a different manner the financial standards adopted at international level by the Basel Committee and have different systems of financial supervision.Due to these significant differences between the two systems, it is very difficult for the EU and US to reach an agreement on common financial standards within the TTIP negotiations. Actually, as the differences in regulation between the two systems are an obstacle to the access of the financial operators of each Party to the market of the other Party, the absence of common standards in this sector could nullify the efficacy of norms of market access that will be probably contained within the TTIP.Moreover, in a risk regulation perspective, considering the weight that the US and EU financial relationship have on the global system and taking account of the effect of destabilization that could be generated by the divergent requirements imposed to the credit institutions on the two sides of the Atlantic, the lack of common financial standards between the EU and US could have a great impact on global financial stability.
The Nutrition and Health Claims Regulation Applies to Commercial Communications Addressed to Health Professionals
Authors: Morpurgo Marco de , Botana Patricia Carmona 
Published: February 2017

Case C-19/15 Verband Sozialer Wettbewerb eV v Innova Vital GmbH (ECJ, 14 July 2016)On 14 July 2016, the Court of Justice delivered its judgment on a request for a preliminary ruling concerning the interpretation of Article 1(2) of Regulation (EC) No 1924/2006 on nutrition and health claims made on foods. The Court ruled for the first time that the Regulation applies to nutrition and health claims made in commercial communications exclusively addressed to health professionals. This represents a major breakthrough as – in a climate of uncertainty – the established industry practice was to interpret Article 1(2) in the sense that the Regulation only applied to commercial communications addressed to final consumers. From now on, food business operators will need to take further precautionary steps to ensure that any information they communicate to health professionals either qualifies as non-commercial or complies with the Regulation. The following case note analyses the content of the judgment and its main implications (authors' summary).
Food Sharing in Europe: Between Regulating Risks and the Risks of Regulating
Authors: Zurek Karolina 
Published: February 2017

AbstractUnderground kitchens, public fridges and local meals at strangers’ homes offer an interesting and economically attractive alternatives to traditional channels of food distribution. The new practices of food sharing facilitated by technological development and using new social media combine an interest in modern engaged consumerism with a promise of more sustainable food chains and waste reduction. The main objective of this article is to map and analyse the risks and regulatory challenges posed by the variety of emerging sharing economy practices in the food sector. Drawing on the identification of the key features of sharing economy and the specificity of food in that context, this article discusses various forms, scales and motivations behind the existing food sharing initiatives. The article describes three main categories of food sharing models, namely harvest sharing, meal sharing and leftover sharing, and illustrates them with concrete examples of networks or platforms. Against this background, the article scrutinizes the major risks and challenges of food sharing, ranging from individual and public health and safety to market fragmentation. Reviewing the available regulatory options to address these risks, and juxtaposing them with the risks stemming out of regulatory intervention as such, the contribution calls for balanced approach to food sharing governance in the European Union.
Timber: Its Identification and Mechanical Properties
Authors: Barling W. H. 
Published: February 2017

In this paper I propose to bring before you a broad outline of our knowledge of the subject, not from the point of view of a botanist, but purely from the point of view of an engineer.Although in ancient, and in fact during all time, timber has been extensively used for constructional purposes, our knowledge of it is comparatively small, whilst the subject itself is very extensive.The reason for these facts is not hard to find. Unfortunately the physicist has not in general had to deal with timber in the progress of physical research, as he has with metals; and the questions which concern the engineer are not in general those with which the botanist deals.There has been comparatively little incentive for engineers to do much work on timber, as before the advent of the aeroplane its application was limited to unimportant parts, except in America and the Colonies, where the cost of metal parts is high. A considerable amount of information has in recent years been published by the American Government Forestry Department; the Government of New South Wales, Australia, have also published a considerable amount of data on Australian timbers.
Haematopoietic stem cells: past, present and future
Authors: Ng Ashley P , Alexander Warren S 
Published: February 2017

AbstractThe discovery and characterisation of haematopoietic stem cells has required decades of research. The identification of adult bone marrow as a source of haematopoietic cells capable of protecting an organism from otherwise lethal irradiation led to the intense search for their identity and characteristics. Using functional assays along with evolving techniques for isolation of haematopoietic cells, haematopoietic stem cell populations were able to be enriched and their characteristics analysed. The key haematopoietic stem cell characteristics of pluripotentiality and the ability for self-renewal have emerged as characteristics of several haematopoietic stem cell populations, including those that have recently challenged the conventional concepts of the haematopoietic hierarchy. Human allogeneic stem cell therapy relies on these functional characteristics of haematopoietic stem cells that can be isolated from peripheral blood, bone marrow or cord blood, with the additional requirement that immunological barriers need to be overcome to allow sustained engraftment while minimising risk of graft-versus-host disease developing in the recipient of transplanted stem cells. Current and future research will continue to focus on the identification of haematopoietic stem cell regulators and methods for in vitro and in vivo stem cell manipulation, including genome editing, to expand the scope, potential and safety of therapy using haematopoietic stem cells.
Dissection of goadsporin biosynthesis by in vitro reconstitution leading to designer analogues expressed in vivo
Authors: Ozaki Taro , Yamashita Kona , Goto Yuki , Shimomura Morito , Hayashi Shohei , Asamizu Shumpei , Sugai Yoshinori , Ikeda Haruo , Suga Hiroaki , Onaka Hiroyasu 
Published: February 2017

AbstractGoadsporin (GS) is a member of ribosomally synthesized and post-translationally modified peptides (RiPPs), containing an N-terminal acetyl moiety, six azoles and two dehydroalanines in the peptidic main chain. Although the enzymes involved in GS biosynthesis have been defined, the principle of how the respective enzymes control the specific modifications remains elusive. Here we report a one-pot synthesis of GS using the enzymes reconstituted in the ‘flexible’ in vitro translation system, referred to as the FIT–GS system. This system allows us to readily prepare not only the precursor peptide from its synthetic DNA template but also 52 mutants, enabling us to dissect the modification determinants of GodA for each enzyme. The in vitro knowledge has also led us to successfully produce designer GS analogues in vivo. The methodology demonstrated in this work is also applicable to other RiPP biosynthesis, allowing us to rapidly investigate the principle of modification events with great ease.
Reconciled rat and human metabolic networks for comparative toxicogenomics and biomarker predictions
Authors: Blais Edik M. , Rawls Kristopher D. , Dougherty Bonnie V. , Li Zhuo I. , Kolling Glynis L. , Ye Ping , Wallqvist Anders , Papin Jason A. 
Published: February 2017

AbstractThe laboratory rat has been used as a surrogate to study human biology for more than a century. Here we present the first genome-scale network reconstruction of Rattus norvegicus metabolism, iRno, and a significantly improved reconstruction of human metabolism, iHsa. These curated models comprehensively capture metabolic features known to distinguish rats from humans including vitamin C and bile acid synthesis pathways. After reconciling network differences between iRno and iHsa, we integrate toxicogenomics data from rat and human hepatocytes, to generate biomarker predictions in response to 76 drugs. We validate comparative predictions for xanthine derivatives with new experimental data and literature-based evidence delineating metabolite biomarkers unique to humans. Our results provide mechanistic insights into species-specific metabolism and facilitate the selection of biomarkers consistent with rat and human biology. These models can serve as powerful computational platforms for contextualizing experimental data and making functional predictions for clinical and basic science applications.
X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
Authors: Olcese Chiara , Patel Mitali P. , Shoemark Amelia , Kiviluoto Santeri , Legendre Marie , Williams Hywel J. , Vaughan Cara K. , Hayward Jane , Goldenberg Alice , Emes Richard D. , Munye Mustafa M. , Dyer Laura , Cahill Thomas , Bevillard Jeremy , Gehrig Corinne , Guipponi Michel , Chantot Sandra , Duquesnoy Philippe , Thomas Lucie , Jeanson Ludovic , Copin Bruno , Tamalet Aline , Thauvin-Robinet Christel , Papon Jean- François , Garin Antoine , Pin Isabelle , Vera Gabriella , Aurora Paul , Fassad Mahmoud R. , Jenkins Lucy , Boustred Christopher , Cullup Thomas , Dixon Mellisa , Onoufriadis Alexandros , Bush Andrew , Chung Eddie M. K. , Antonarakis Stylianos E. , Loebinger Michael R. , Wilson Robert , Armengot Miguel , Escudier Estelle , Hogg Claire ,   UK10K Rare Group, Al-Turki Saeed , Anderson Carl , Antony Dinu , Barroso Inês , Beales Philip L. , Bentham Jamie , Bhattacharya Shoumo , Carss Keren , Chatterjee Krishna , Cirak Sebahattin , Cosgrove Catherine , Allan Daly , Durbin Richard , Fitzpatrick David , Floyd Jamie , Foley A. Reghan , Franklin Chris , Futema Marta , Humphries Steve E. , Hurles Matt , McCarthy Shane , Muddyman Dawn , Muntoni Francesco , Parker Victoria , Payne Felicity , Plagnol Vincent , Raymond Lucy , Savage David B. , Scambler Peter J. , Schmidts Miriam , Semple Robert , Serra Eva , Stalker Jim , van Kogelenberg Margriet , Vijayarangakannan Parthiban , Walter Klaudia , Amselem Serge , Sun Zhaoxia , Bartoloni Lucia , Blouin Jean-Louis , Mitchison Hannah M. 
Published: February 2017

AbstractBy moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2–DNAAF4–HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins.
Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging
Authors: Cuccarese Michael F. , Dubach J. Matthew , Pfirschke Christina , Engblom Camilla , Garris Christopher , Miller Miles A. , Pittet Mikael J. , Weissleder Ralph 
Published: February 2017

AbstractInvolvement of the immune system in tumour progression is at the forefront of cancer research. Analysis of the tumour immune microenvironment has yielded a wealth of information on tumour biology, and alterations in some immune subtypes, such as tumour-associated macrophages (TAM), can be strong prognostic indicators. Here, we use optical tissue clearing and a TAM-targeting injectable fluorescent nanoparticle (NP) to examine three-dimensional TAM composition, tumour-to-tumour heterogeneity, response to colony-stimulating factor 1 receptor (CSF-1R) blockade and nanoparticle-based drug delivery in murine pulmonary carcinoma. The method allows for rapid tumour volume assessment and spatial information on TAM infiltration at the cellular level in entire lungs. This method reveals that TAM density was heterogeneous across tumours in the same animal, overall TAM density is different among separate pulmonary tumour models, nanotherapeutic drug delivery correlated with TAM heterogeneity, and successful response to CSF-1R blockade is characterized by enhanced TAM penetration throughout and within tumours.
A CAF40-binding motif facilitates recruitment of the CCR4-NOT complex to mRNAs targeted by Drosophila Roquin
Authors: Sgromo Annamaria , Raisch Tobias , Bawankar Praveen , Bhandari Dipankar , Chen Ying , Kuzuoğlu-Öztürk Duygu , Weichenrieder Oliver , Izaurralde Elisa 
Published: February 2017

AbstractHuman (Hs) Roquin1 and Roquin2 are RNA-binding proteins that promote mRNA target degradation through the recruitment of the CCR4-NOT deadenylase complex and are implicated in the prevention of autoimmunity. Roquin1 recruits CCR4-NOT via a C-terminal region that is not conserved in Roquin2 or in invertebrate Roquin. Here we show that Roquin2 and Drosophila melanogaster (Dm) Roquin also interact with the CCR4-NOT complex through their C-terminal regions. The C-terminal region of Dm Roquin contains multiple motifs that mediate CCR4-NOT binding. One motif binds to the CAF40 subunit of the CCR4-NOT complex. The crystal structure of the Dm Roquin CAF40-binding motif (CBM) bound to CAF40 reveals that the CBM adopts an α-helical conformation upon binding to a conserved surface of CAF40. Thus, despite the lack of sequence conservation, the C-terminal regions of Roquin proteins act as an effector domain that represses the expression of mRNA targets via recruitment of the CCR4-NOT complex.
Cryptic bioactivity capacitated by synthetic hybrid plant peptides
Authors: Hirakawa Yuki , Shinohara Hidefumi , Welke Kai , Irle Stephan , Matsubayashi Yoshikatsu , Torii Keiko U. , Uchida Naoyuki 
Published: February 2017

AbstractEvolution often diversifies a peptide hormone family into multiple subfamilies, which exert distinct activities by exclusive interaction with specific receptors. Here we show that systematic swapping of pre-existing variation in a subfamily of plant CLE peptide hormones leads to a synthetic bifunctional peptide that exerts activities beyond the original subfamily by interacting with multiple receptors. This approach provides new insights into the complexity and specificity of peptide signalling.
Soil networks become more connected and take up more carbon as nature restoration progresses
Authors: Morriën Elly , Hannula S. Emilia , Snoek L. Basten , Helmsing Nico R. , Zweers Hans , de Hollander Mattias , Soto Raquel Luján , Bouffaud Marie-Lara , Buée Marc , Dimmers Wim , Duyts Henk , Geisen Stefan , Girlanda Mariangela , Griffiths Rob I. , Jørgensen Helene-Bracht , Jensen John , Plassart Pierre , Redecker Dirk , Schmelz Rűdiger M , Schmidt Olaf , Thomson Bruce C. , Tisserant Emilie , Uroz Stephane , Winding Anne , Bailey Mark J. , Bonkowski Michael , Faber Jack H. , Martin Francis , Lemanceau Philippe , de Boer Wietse , van Veen Johannes A. , van der Putten Wim H. 
Published: February 2017

AbstractSoil organisms have an important role in aboveground community dynamics and ecosystem functioning in terrestrial ecosystems. However, most studies have considered soil biota as a black box or focussed on specific groups, whereas little is known about entire soil networks. Here we show that during the course of nature restoration on abandoned arable land a compositional shift in soil biota, preceded by tightening of the belowground networks, corresponds with enhanced efficiency of carbon uptake. In mid- and long-term abandoned field soil, carbon uptake by fungi increases without an increase in fungal biomass or shift in bacterial-to-fungal ratio. The implication of our findings is that during nature restoration the efficiency of nutrient cycling and carbon uptake can increase by a shift in fungal composition and/or fungal activity. Therefore, we propose that relationships between soil food web structure and carbon cycling in soils need to be reconsidered.
Cooling a mechanical resonator with nitrogen-vacancy centres using a room temperature excited state spin–strain interaction
Authors: MacQuarrie E. R. , Otten M. , Gray S. K. , Fuchs G. D. 
Published: February 2017

AbstractCooling a mechanical resonator mode to a sub-thermal state has been a long-standing challenge in physics. This pursuit has recently found traction in the field of optomechanics in which a mechanical mode is coupled to an optical cavity. An alternate method is to couple the resonator to a well-controlled two-level system. Here we propose a protocol to dissipatively cool a room temperature mechanical resonator using a nitrogen-vacancy centre ensemble. The spin ensemble is coupled to the resonator through its orbitally-averaged excited state, which has a spin–strain interaction that has not been previously studied. We experimentally demonstrate that the spin–strain coupling in the excited state is 13.5±0.5 times stronger than the ground state spin–strain coupling. We then theoretically show that this interaction, combined with a high-density spin ensemble, enables the cooling of a mechanical resonator from room temperature to a fraction of its thermal phonon occupancy.
Killing by Type VI secretion drives genetic phase separation and correlates with increased cooperation
Authors: McNally Luke , Bernardy Eryn , Thomas Jacob , Kalziqi Arben , Pentz Jennifer , Brown Sam P. , Hammer Brian K. , Yunker Peter J. , Ratcliff William C. 
Published: February 2017

AbstractBy nature of their small size, dense growth and frequent need for extracellular metabolism, microbes face persistent public goods dilemmas. Genetic assortment is the only general solution stabilizing cooperation, but all known mechanisms structuring microbial populations depend on the availability of free space, an often unrealistic constraint. Here we describe a class of self-organization that operates within densely packed bacterial populations. Through mathematical modelling and experiments withVibrio cholerae,we show how killing adjacent competitors via the Type VI secretion system (T6SS) precipitates phase separation via the ‘Model A’ universality class of order-disorder transition mediated by killing. We mathematically demonstrate that T6SS-mediated killing should favour the evolution of public goods cooperation, and empirically support this prediction using a phylogenetic comparative analysis. This work illustrates the twin role played by the T6SS, dealing death to local competitors while simultaneously creating conditions potentially favouring the evolution of cooperation with kin.
Foxn1-β5t transcriptional axis controls CD8+ T-cell production in the thymus
Authors: Uddin Muhammad Myn , Ohigashi Izumi , Motosugi Ryo , Nakayama Tomomi , Sakata Mie , Hamazaki Jun , Nishito Yasumasa , Rode Immanuel , Tanaka Keiji , Takemoto Tatsuya , Murata Shigeo , Takahama Yousuke 
Published: February 2017

AbstractThe thymus is an organ that produces functionally competent T cells that protect us from pathogens and malignancies. Foxn1 is a transcription factor that is essential for thymus organogenesis; however, the direct target for Foxn1 to actuate thymic T-cell production is unknown. Here we show that a Foxn1-binding cis-regulatory element promotes the transcription of β5t, which has an essential role in cortical thymic epithelial cells to induce positive selection of functionally competent CD8+ T cells. A point mutation in this genome element results in a defect in β5t expression and CD8+ T-cell production in mice. The results reveal a Foxn1-β5t transcriptional axis that governs CD8+ T-cell production in the thymus.