bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cassava shrunken-2 homolog MeAPL3 determines storage root starch and dry matter content and modulates storage root postharvest physiological deterioration
Authors: Beyene Getu , Chauhan Raj Deepika , Gehan Jackson , Siritunga Dimuth , Taylor Nigel 
Published: April 2020

Abstract
Key message
Among the five cassava isoforms (MeAPL1–MeAPL5), MeAPL3 is responsible for determining storage root starch content. Degree of storage root postharvest physiological deterioration (PPD) is directly correlated with starch content.

Abstract
AGPase is heterotetramer composed of two small and two large subunits each coded by small gene families in higher plants. Studies in cassava (Manihot esculenta) identified and characterized five isoforms of Manihot esculenta ADP-glucose pyrophosphorylase large subunit (MeAPL1–MeAPL5) and employed virus induced gene silencing (VIGS) to show that MeAPL3 is the key isoform responsible for starch and dry matter accumulation in cassava storage roots. Silencing of MeAPL3 in cassava through stable transgenic lines resulted in plants displaying significant reduction in storage root starch and dry matter content (DMC) and induced a distinct phenotype associated with increased petiole/stem angle, resulting in a droopy leaf phenotype. Plants with reduced starch and DMC also displayed significantly reduced or no postharvest physiological deterioration (PPD) compared to controls and lines with high DMC and starch content. This provides strong evidence for direct relationships between starch/dry matter content and its role in PPD and canopy architecture traits in cassava.
Another look at value and momentum: volatility spillovers
Authors: Grobys Klaus , Vähämaa Sami 
Published: April 2020

AbstractThis paper examines volatility interdependencies between value and momentum returns. Using U.S. data over the period 1926–2015, we document persistent periods of low and high volatility spillovers between value and momentum strategies. Moreover, we find that the intensity of the volatility spillovers may change substantially in very short periods of time and that these shifts in spillover intensity can be linked to prominent economic events and financial market turmoil. Our results further demonstrate that value returns increase and momentum returns decrease monotonically with increasing volatility spillovers between the two strategies. Given this linkage between spillover intensity and returns, we propose a simple trading strategy which utilizes a volatility spillover index for allocating funds between value and momentum portfolios. The proposed trading strategy outperforms value and momentum strategies and generates payoffs that are not subject to option-like behavior.
Needs and cost-effectiveness in health care priority setting
Authors: Gustavsson Erik , Tinghög Gustav 
Published: April 2020

AbstractHow to balance the maximization of health and concerns for the worse off remains a challenge for health care decision makers when setting priorities. In regulatory guidelines these concerns are typically specified in terms of priority setting according to needs and priority setting according to cost-effectiveness. Still, it is often unclear when and why needs and cost-effectiveness diverge or overlap as guiding priority setting principles in practice. We conduct a comparative analysis of need and cost-effectiveness in the context of health care priority setting. Based on theories of distributive justice we specify three normative interpretations of need and explicate how these relate to the normative basis for cost-effectiveness analysis. Using priority-setting dilemmas we then move on to explicate when and why need and cost-effectiveness diverge as priority-setting principles. We find that: (i) although principles of need and cost-effectiveness may recommend the same allocation of resources the underlying reason for an allocation is different; (ii) while they both may give weight to patients who are worse off they do so in different ways and to different degree; and (iii) whereas cost-effectiveness clearly implies the aggregation of benefits across individuals principles of needs give no guidance with regard to if, and if so, how needs should be aggregated. Priority setting according to needs or cost-effectiveness does not necessarily recommend different allocations of resources. Thus, the normative conflict between them, often highlighted in practice, seems exaggerated. For health policy this is important knowledge because unclear conceptions may obstruct an informed public discussion. Moreover, if decision-makers are to properly account for both principles they need to recognize the inconsistencies as well as similarities between the two.
Measuring happiness increases happiness
Authors: Roessler Jannik , Gloor Peter A. 
Published: April 2020

AbstractHappiness has been an overarching goal of mankind at least since Aristotle spoke of Eudaimonia. However measuring happiness has been elusive and until now has almost exclusively been done by asking survey questions about self-perceived happiness. We propose a novel approach, tracking happiness and stress through changes in body signals with a smartwatch, the “Happimeter”. It predicts individual emotions from sensor data collected by an Android Wear smartwatch, such as acceleration, heartbeat, and activity. The Happimeter was used over three months in the innovation lab of a bank with 22 employees to measure individual happiness, activity, and stress. The participants were randomly divided into an experimental and a control group of similar size. Both groups wore the watch and entered their subjective happiness, activity and stress levels several times a day. The user-entered ratings were then used to train a machine learning system using the sensors of the smartwatch to subsequently automatically predict happiness, activity, and stress. The experimental group received ongoing feedback about their mood and which activity, sensor signals, or other people, made them happier or unhappier, while the control group did not get any feedback about their predicted and manually entered emotions. Just like in quantum physics we observed a “Heisenberg Effect”, where the participants made aware of their measurements changed their behavior: Members of the experimental group that received happiness feedback were 16% happier, and 26% more active than the control group at the end of the experiment. No effect was observed for stress.
ATM-deficient lung, prostate and pancreatic cancer cells are acutely sensitive to the combination of olaparib and the ATR inhibitor AZD6738
Authors: Jette Nicholas R. , Radhamani Suraj , Ye Ruiqiong , Yu Yaping , Arthur Greydon , Goutam Siddhartha , Bismar Tarek A. , Kumar Mehul , Bose Pinaki , Yip Steven , Kolinsky Michael , Lees-Miller Susan P. 
Published: April 2020

AbstractThe Ataxia Telangiectasia Mutated (ATM) protein kinase is mutated in several human cancers, presenting potential opportunities for targeted cancer therapy. We previously reported that the poly-ADP-ribose polymerase (PARP) inhibitor olaparib induces transient G2 arrest but not cell death in ATM-deficient lung cancer cells, while the combination of olaparib with the ATM- and Rad3-related (ATR) inhibitor VE-821 induced cell death. Here, we show that combination of olaparib plus the clinically relevant ATR inhibitor AZD6738 also induces cell death in ATM-deficient lung, prostate and pancreatic cancer cells with little effect on their ATM-proficient counterparts. Together, our data suggest that lung, prostate and pancreatic patients whose tumours exhibit loss or inactivation of ATM may benefit from combination of a PARP inhibitor plus an ATR inhibitor.
The Action for Damages as a Fundamental Rights Remedy: Holding Frontex Liable
Authors: Fink Melanie 
Published: April 2020

AbstractFrontex has become one of the major players in European external border management. As its powers and resources have increased, so have the challenges surrounding its compliance with fundamental rights. A major concern continues to be how to ensure legal accountability for fundamental rights violations that occur in the context of its activities. While Member States can be held accountable before their own national courts and before international courts, neither of these options are available in relation to Frontex. But it can be brought before the Court of Justice of the European Union to account for the conformity of its conduct with EU law. This Article explores the potential of the EU action for damages to offer a remedy for fundamental rights violations committed by Frontex. It identifies where public liability law falls short of providing a remedy for fundamental rights violations committed by EU bodies, explores the possibilities to close that gap, and assesses the implications this has for Frontex’s liability. The Article argues that the action for damages may be the means to close the accountability gap in the specific case of Frontex, but also more generally in circumstances where EU administration is delivered in the form of informal or factual conduct. If it is to fulfill that role, the CJEU would have to lower the threshold for EU liability where fundamental rights are concerned.
Holding the European Asylum Support Office Accountable for its role in Asylum Decision-Making: Mission Impossible?
Authors: Tsourdi Evangelia (Lilian) 
Published: April 2020

AbstractThe Common European Asylum System (CEAS) seeks to harmonize national asylum procedures. The initial implementation design of the CEAS, reflective of the theory of executive federalism, foresaw that national authorities were to conduct asylum processing and implement the harmonized norms. The implementation design of the EU asylum policy has, nevertheless, started to shift. An integrated European administration is emerging. One area this is pronounced in is asylum decision-making, where patterns of joint implementation have surfaced. This term broadly refers to staff and experts deployed by the European Asylum Support Office (EASO), an EU agency, working alongside national administrators, including on the processing of asylum claims. This Article scrutinizes the emergence of joint implementation patterns in EU asylum policy and the resulting accountability challenge, drawing both from legal analysis and political science theories. I also refer to administrative practice as documented in secondary sources. EASO is currently subject to a mosaic of accountability processes. Two main pitfalls emerge: the intricate balance between accountability and independence; and accessibility for the individual. Against this backdrop, I focus on extra-judicial accountability through the European Ombudsman which, combined with the envisaged internal “individual complaints mechanism” within EASO, could go some way in ensuring applicants’ procedural rights.
On the relaxation of integral functionals depending on the symmetrized gradient
Authors: Kosiba Kamil , Rindler Filip 
Published: April 2020

AbstractWe prove results on the relaxation and weak* lower semicontinuity of integral functionals of the form$${\cal F}[u]: = \int_\Omega f \left( {\displaystyle{1 \over 2}\left( {\nabla u(x) + \nabla u{(x)}^T} \right)} \right) \,{\rm d}x,\quad u:\Omega \subset {\mathbb R}^d\to {\mathbb R}^d,$$over the space BD(Ω) of functions of bounded deformation or over the Temam–Strang space$${\rm U}(\Omega ): = \left\{ {u\in {\rm BD}(\Omega ):\;\,{\rm div}\,u\in {\rm L}^2(\Omega )} \right\},$$depending on the growth and shape of the integrandf. Such functionals are interesting, for example, in the study of Hencky plasticity and related models.
STEPPED-COMBUSTION14C DATING IN LOESS-PALEOSOL SEDIMENT
Authors: Cheng Peng , Fu Yunchong 
Published: April 2020

ABSTRACTIn this study, low temperature (room temperature, 400°C LT) and high temperature (400–900°C HT) of bulk organic carbon samples were dated from two loess and paleosol profiles. The results showed that radiocarbon (14C) dates of the LT were younger than HT fractions, indicating effect of younger contamination from overlying layers. The δ13C variation of the HT fraction appears to respond much more sensitively to climate change, and14C ages of HT fraction can produce reasonable14C ages from a younger layer, but it is very difficult to obtain reliable14C ages from older layer as a result of uncomplete removal of young carbon.
Landslide Disparities, Flume Discoveries, and Oso Despair
Authors: Iverson Richard M. 
Published: April 2020

AbstractLandslide dynamics is the branch of science that seeks to understand the motion of landslides by applying Newton's laws. This memoir focusses on a 40‐year effort to understand motion of highly mobile—and highly lethal—landslides such as debris avalanches and debris flows. A major component of this work entailed development and operation of the U.S. Geological Survey debris flow flume, a unique, large‐scale experimental facility in Oregon. Experiments there yielded new insights that informed development of mathematical models that were aimed not only at explaining landslide dynamics but also at evaluating landslide and debris flow hazards. The most sophisticated of these models, called D‐Claw, found its first practical application during investigations of the 2014 Oso, Washington, landslide disaster. That event provided indelible lessons about the utility and sociology of science in the real world.
Molecular Characterization of Organosulfates in Highly Polluted Atmosphere Using Ultra‐High‐Resolution Mass Spectrometry
Authors: Cai Dongmei , Wang Xinke , Chen Jianmin , Li Xiang 
Published: April 2020

AbstractOrganosulfates (OSs) have recently been observed to be a potentially important constituent of secondary organic aerosol (SOA); however, their molecular characterization in highly polluted atmospheres has not been probed in detail. This study thoroughly presents the characterization of OSs in polluted air and demonstrates their seasonal and diurnal variations, formation mechanisms, and contributions to organic aerosol. Atmospheric PM2.5 samples were collected from an urban Shanghai site across the winter and summer of 2017. OSs were characterized by ultra‐high‐performance liquid chromatography (UHPLC) coupled with Orbitrap mass spectrometry (MS). Based on exact mass formulae in conjunction with previous chamber studies, hundreds of sulfur‐containing compounds were tentatively identified as OSs. The number and abundance of OSs increased significantly during pollution episodes. The OSs in the clean aerosol samples were dominant in biogenic products, whereas the OSs in the polluted winter samples had distinctive anthropogenic characteristics. Aromatics and long‐chain alkanes from anthropogenic emissions might be their precursors. By using synthesized standards, the total concentrations of 14 quantified OSs ranged 21.6–161 ng m−3 in summer and 5.85–84.3 ng m−3 in winter, respectively. Among these OSs, glycolic acid sulfate was the most abundant species (1.13–122 ng m−3). Further analysis of their seasonal and diurnal variations suggests possible contributions from multiple formation mechanisms, including acid‐catalyzed and NO3‐initiated oxidation reactions. Our results highlight that increased anthropogenic pollutant emissions (e.g., NOx and SO2) can significantly enhance the SOA burden in biogenically influenced urban areas.
Zinc finger protein 703 induces EMT and sorafenib resistance in hepatocellular carcinoma by transactivating CLDN4 expression
Authors: Wang Hao , Xu Hongfa , Ma Feng , Zhan Meixiao , Yang Xiangyu , Hua Shengni , Li Wei , Li Yong , Lu Ligong 
Published: April 2020

AbstractMetastasis is one of the most common reasons of hepatocellular carcinoma (HCC) death; however, the molecular mechanism underlying HCC metastasis remains incompletely defined. Here we report a new function of Zinc Finger Protein 703 (ZNF703), a member of the NET/NlZ family of zinc finger transcription factors, in promoting hepatocellular carcinoma metastasis. We demonstrated that the overexpression of ZNF703 in human HCC tissue is correlated with tumor metastasis and recurrence, it is also related with the prognosis and survival rate of patients. ZNF703 overexpression promotes HCC progression in vitro and in vivo, whereas ZNF703 knockdown has the opposite effect. In addition, ZNF703 induces epithelialmesenchymal transition (EMT) via directly binding to the CLDN4 promoter and transactivating CLDN4 expression. Downregulation of CLDN4 can attenuate ZNF703-mediated HCC metastasis, whereas upregulation of CLDN4 can reverse the decreased metastasis induced by ZNF703 knockdown. Our data revealed that ZNF703 expression is correlated with CLDN4 level, the overexpression of both ZNF703 and CLDN4 are leaded to poorer prognosis of patients with HCC. Moreover, ZNF703 knockdown can enhance the sensitivity of HCC cell to sorafenib, whereas ZNF703 overexpression has the opposite effect. These results suggested that ZNF703 might be a potential target for cancer therapies and a candidate prognostic biomarker for predicting whether patients with HCC are befitting for sorafenib treatment.
Mechanical cleaning of graphene using in situ electron microscopy
Authors: Schweizer Peter , Dolle Christian , Dasler Daniela , Abellán Gonzalo , Hauke Frank , Hirsch Andreas , Spiecker Erdmann 
Published: April 2020

AbstractAvoiding and removing surface contamination is a crucial task when handling specimens in any scientific experiment. This is especially true for two-dimensional materials such as graphene, which are extraordinarily affected by contamination due to their large surface area. While many efforts have been made to reduce and remove contamination from such surfaces, the issue is far from resolved. Here we report on an in situ mechanical cleaning method that enables the site-specific removal of contamination from both sides of two dimensional membranes down to atomic-scale cleanliness. Further, mechanisms of re-contamination are discussed, finding surface-diffusion to be the major factor for contamination in electron microscopy. Finally the targeted, electron-beam assisted synthesis of a nanocrystalline graphene layer by supplying a precursor molecule to cleaned areas is demonstrated.
Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans
Authors: Wei Wei , Pagnamenta Alistair T. , Gleadall Nicholas , Sanchis-Juan Alba , Stephens Jonathan , Broxholme John , Tuna Salih , Odhams Christopher A. ,   Genomics England Research Consortium, Ambrose J. C. , Baple E. L. , Bleda M. , Boardman-Pretty F. , Boissiere J. M. , Boustred C. R. , Caulfield M. J. , Chan G. C. , Craig C. E. H. , Daugherty L. C. , de Burca A. , Devereau A. , Elgar G. , Foulger R. E. , Fowler T. , Furió-Tarí P. , Hackett J. M. , Halai D. , Holman J. E. , Hubbard T. J. P. , Jackson R. , Kasperaviciute D. , Kayikci M. , Lahnstein L. , Lawson K. , Leigh S. E. A. , Leong I. U. S. , Lopez F. J. , Maleady-Crowe F. , Mason J. , McDonagh E. M. , Moutsianas L. , Mueller M. , Murugaesu N. , Need A. C. , Odhams C. A. , Patch C. , Perez-Gil D. , Polychronopoulos D. , Pullinger J. , Rahim T. , Rendon A. , Riesgo-Ferreiro P. , Rogers T. , Ryten M. , Savage K. , Sawant K. , Scott R. H. , Siddiq A. , Sieghart A. , Smedley D. , Smith K. R. , Sosinsky A. , Spooner W. , Stevens H. E. , Stuckey A. , Sultana R. , Thomas E. R. A. , Thompson S. R. , Tregidgo C. , Tucci A. , Walsh E. , Watters S. A. , Welland M. J. , Williams E. , Witkowska K. , Wood S. M. , Zarowiecki M. ,   NIHR BioResource, Sanchis-Juan Alba , Stephens Jonathan , Tuna Salih , Turro Ernest , Chinnery Patrick F. , Fratter Carl , Turro Ernest , Caulfield Mark J. , Taylor Jenny C. , Rahman Shamima , Chinnery Patrick F. 
Published: April 2020

AbstractSeveral strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored a ‘heteroplasmic haplotype’ consistent with biparental transmission. Here we report a similar genetic signature in 7 of 11,035 trios, with allelic fractions of 5–25%, implying biparental inheritance of mtDNA in 0.06% of offspring. However, analysing the nuclear whole genome sequence, we observe likely large rare or unique nuclear-mitochondrial DNA segments (mega-NUMTs) transmitted from the father in all 7 families. Independently detecting mega-NUMTs in 0.13% of fathers, we see autosomal transmission of the haplotype. Finally, we show the haplotype allele fraction can be explained by complex concatenated mtDNA-derived sequences rearranged within the nuclear genome. We conclude that rare cryptic mega-NUMTs can resemble paternally mtDNA heteroplasmy, but find no evidence of paternal transmission of mtDNA in humans.
Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation
Authors: Laurien Lucie , Nagata Masahiro , Schünke Hannah , Delanghe Tom , Wiederstein Janica L. , Kumari Snehlata , Schwarzer Robin , Corona Teresa , Krüger Marcus , Bertrand Mathieu J. M. , Kondylis Vangelis , Pasparakis Manolis 
Published: April 2020

AbstractReceptor interacting protein kinase 1 (RIPK1) regulates cell death and inflammatory responses downstream of TNFR1 and other receptors, and has been implicated in the pathogenesis of inflammatory and degenerative diseases. RIPK1 kinase activity induces apoptosis and necroptosis, however the mechanisms and phosphorylation events regulating RIPK1-dependent cell death signaling remain poorly understood. Here we show that RIPK1 autophosphorylation at serine 166 plays a critical role for the activation of RIPK1 kinase-dependent apoptosis and necroptosis. Moreover, we show that S166 phosphorylation is required for RIPK1 kinase-dependent pathogenesis of inflammatory pathologies in vivo in four relevant mouse models. Mechanistically, we provide evidence that trans autophosphorylation at S166 modulates RIPK1 kinase activation but is not by itself sufficient to induce cell death. These results show that S166 autophosphorylation licenses RIPK1 kinase activity to induce downstream cell death signaling and inflammation, suggesting that S166 phosphorylation can serve as a reliable biomarker for RIPK1 kinase-dependent pathologies.
Developing a new class of engineered live bacterial therapeutics to treat human diseases
Authors: Charbonneau Mark R. , Isabella Vincent M. , Li Ning , Kurtz Caroline B. 
Published: April 2020

AbstractA complex interplay of metabolic and immunological mechanisms underlies many diseases that represent a substantial unmet medical need. There is an increasing appreciation of the role microbes play in human health and disease, and evidence is accumulating that a new class of live biotherapeutics comprised of engineered microbes could address specific mechanisms of disease. Using the tools of synthetic biology, nonpathogenic bacteria can be designed to sense and respond to environmental signals in order to consume harmful compounds and deliver therapeutic effectors. In this perspective, we describe considerations for the design and development of engineered live biotherapeutics to achieve regulatory and patient acceptance.
A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes
Authors: Qu Wenchao , Hu Bao , Babich John W. , Waterhouse Nicole , Dooley Marybeth , Ponnala Shashikanth , Urgiles Julie 
Published: April 2020

AbstractCarbon-11 (11C) is one of the most ideal positron emitters for labeling bioactive molecules for molecular imaging studies. The lack of convenient and fast incorporation methods to introduce 11C into organic molecules often hampers the use of this radioisotope. Here, a fluoride-mediated desilylation (FMDS) 11C-labeling approach is reported. This method relies on thermodynamically favored Si-F bond formation to generate a carbanion, therefore enabling the highly efficient and speedy incorporation of [11C]CO2 and [11C]CH3I into molecules with diversified structures. It provides facile and rapid access to 11C-labeled compounds with carbon-11 attached at various hybridized carbons as well as oxygen, sulfur and nitrogen atoms with broad functional group tolerance. The exemplified syntheses of several biologically and clinically important radiotracers illustrates the potentials of this methodology.