bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Dynamic Differentiation’: The Principles of CBDR-RC, Progression and Highest Possible Ambition in the Paris Agreement
Authors: Voigt Christina , Ferreira Felipe 
Published: October 2016

AbstractThe Paris Agreement has struck a careful balance between the need for ambitious and effective climate action and for fair effort sharing among parties based on differentiation. This article provides an overview of the negotiation history of differentiation and analyzes the ‘dynamic differentiation’ as built into the architecture of the Agreement. While being set against the normative background of the United Nations Framework Convention on Climate Change (UNFCCC), the Paris Agreement adopts a more diversified way of differential treatment among parties, approaching it in three complementary ways: firstly, on a principled basis, reflecting common but differentiated responsibilities and respective capabilities (CBDR-RC), in the light of different national circumstances; secondly, in the content of its articles, in particular on mitigation, finance and transparency; and thirdly, on the basis of the principles of progression and highest possible ambition, which represent new and dynamic aspects of differentiation. The authors argue that ‘highest possible ambition’ is reflective of a duty of care that states now need to exercise. It implies a due diligence standard, which requires each government to act in proportion to the risk at stake and to take all appropriate and adequate climate measures according to its responsibility and its best capabilities. By expecting parties to apply this standard at each successive preparation of nationally determined contributions (NDCs), and to progress beyond previous ones, the Paris Agreement has set up reiterative processes, an ‘international normative pull’ and a collective learning environment. This, in turn, creates a reflexive approach to parties’ determination of effort, promoting the evolution of voluntary cooperative behaviour.
‘Common But Differentiated Responsibilities’ in the National Courts: Lessons fromUrgendav.The Netherlands
Authors: Ferreira Patrícia Galvão 
Published: October 2016

AbstractThe landmark 2015 decision by the Hague District Court inUrgendav.The Netherlandsrepresents the first time a national court has expressly used the international environmental law (IEL) principle of common but differentiated responsibilities and capabilities (CBDRs) of the climate regime as a complementary tool to interpret the scope of a state’s climate obligations under domestic law. This article highlights that despite the marked engagement of national courts with IEL in recent decades (including engaging with principles such as sustainable development, polluter pays, intergenerational equity, and precaution), until this decision CBDRs had remained outside the purview of environmental law jurisprudence at the national level. The article examines how the Hague Court used CBDRs to help address two common barriers to climate liability: causation and the ‘political question’ doctrine. The article argues that the Court was able to find normative content in a core element of the climate-related CBDRs: the ‘leadership’ role of developed countries in climate action. This core element has remained remarkably consensual throughout the contested history of CBDRs in the climate regime – a history that has gained a new chapter with the signature of the Paris Agreement in December 2015. The article concludes thatUrgendav.The Netherlandsmay serve as a starting point for a more productive and extensive use of CBDRs in climate litigation, provided litigants make more explicit use of the persuasive authority of the principle.
Cooperation for Climate Mitigation in Amazonia: Brazil’s Emerging Role as a Regional Leader
Authors: Tigre Maria Antonia 
Published: October 2016

AbstractSince their inception, climate change negotiations have stalled because of the scope of parties’ mitigation responsibilities under the United Nations Framework Convention on Climate Change (UNFCCC). The concept of common but differentiated responsibilities and respective capabilities (CBDR-RC) became a core principle of the framework to ensure consensus on a global climate policy in 1992 and to promote differentiation. By letting each country assess its current responsibilities and capacities for climate mitigation through their nationally determined contributions (NDCs), the Paris Agreement has built on the principle of CBDR-RC and promoted self-differentiation. As the concept evolved, the role of emerging economies has been a particular focus of discussions. Academia is still grappling with the revised meaning of CBDR-RC and the newly introduced NDCs. This article contributes to the discussion by analyzing the role of emerging economies in climate governance through the lens of regional responsibility. In particular, it discusses how cooperation can be a more effective way to ensure differentiation, especially by distinguishing emerging economies from other developing countries with fewer capacities. The article uses the Amazon rainforest as a case study, discussing Brazil’s role within the region. Building on lessons from regional schemes that have successfully promoted climate mitigation, the article looks at the Amazon Cooperation Treaty Organization (ACTO) as an avenue for enhanced cooperation at the regional level.
A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence
Authors:   for the RESUME trialists, Tefferi A , Al-Ali H K , Barosi G , Devos T , Gisslinger H , Jiang Q , Kiladjian J-J , Mesa R , Passamonti F , Ribrag V , Schiller G , Vannucchi A M , Zhou D , Reiser D , Zhong J , Gale R P 
Published: October 2016

AbstractRBC-transfusion dependence is common in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. The objective of this study was to determine the rates of RBC-transfusion independence after therapy with pomalidomide vs placebo in persons with MPN-associated myelofibrosis and RBC-transfusion dependence. Two hundred and fifty-two subjects (intent-to-treat (ITT) population) including 229 subjects confirmed by central review (modified ITT population) were randomly assigned (2:1) to pomalidomide or placebo. Trialists and subjects were blinded to treatment allocation. Primary end point was proportion of subjects achieving RBC-transfusion independence within 6 months. One hundred and fifty-two subjects received pomalidomide and 77 placebo. Response rates were 16% (95% confidence interval (CI), 11, 23%) vs 16% (8, 26%;P=0.87). Response in the pomalidomide cohort was associated with ⩽4 U RBC/28 days (odds ratio (OR)=3.1; 0.9, 11.1), age ⩽65 (OR=2.3; 0.9, 5.5) and type of MPN-associated myelofibrosis (OR=2.6; 0.7, 9.5). Responses in the placebo cohort were associated with ⩽4 U RBC/28 days (OR=8.6; 0.9, 82.3), white blood cell at randomization >25 × 109/l (OR=4.9; 0.8, 28.9) and interval from diagnosis to randomization >2 years (OR=4.9; 1.1, 21.9). Pomalidomide was associated with increased rates of oedema and neutropenia but these adverse effects were manageable. Pomalidomide and placebo had similar RBC-transfusion-independence response rates in persons with MPN-associated RBC-transfusion dependence.
Diversity-oriented synthetic strategy for developing a chemical modulator of protein–protein interaction
Authors: Kim Jonghoon , Jung Jinjoo , Koo Jaeyoung , Cho Wansang , Lee Won Seok , Kim Chanwoo , Park Wonwoo , Park Seung Bum 
Published: October 2016

AbstractDiversity-oriented synthesis (DOS) can provide a collection of diverse and complex drug-like small molecules, which is critical in the development of new chemical probes for biological research of undruggable targets. However, the design and synthesis of small-molecule libraries with improved biological relevance as well as maximized molecular diversity represent a key challenge. Herein, we employ functional group-pairing strategy for the DOS of a chemical library containing privileged substructures, pyrimidodiazepine or pyrimidine moieties, as chemical navigators towards unexplored bioactive chemical space. To validate the utility of this DOS library, we identify a new small-molecule inhibitor of leucyl-tRNA synthetase–RagD protein–protein interaction, which regulates the amino acid-dependent activation of mechanistic target of rapamycin complex 1 signalling pathway. This work highlights that privileged substructure-based DOS strategy can be a powerful research tool for the construction of drug-like compounds to address challenging biological targets.
Thousands of microbial genomes shed light on interconnected biogeochemical processes in an aquifer system
Authors: Anantharaman Karthik , Brown Christopher T. , Hug Laura A. , Sharon Itai , Castelle Cindy J. , Probst Alexander J. , Thomas Brian C. , Singh Andrea , Wilkins Michael J. , Karaoz Ulas , Brodie Eoin L. , Williams Kenneth H. , Hubbard Susan S. , Banfield Jillian F. 
Published: October 2016

AbstractThe subterranean world hosts up to one-fifth of all biomass, including microbial communities that drive transformations central to Earth’s biogeochemical cycles. However, little is known about how complex microbial communities in such environments are structured, and how inter-organism interactions shape ecosystem function. Here we apply terabase-scale cultivation-independent metagenomics to aquifer sediments and groundwater, and reconstruct 2,540 draft-quality, near-complete and complete strain-resolved genomes that represent the majority of known bacterial phyla as well as 47 newly discovered phylum-level lineages. Metabolic analyses spanning this vast phylogenetic diversity and representing up to 36% of organisms detected in the system are used to document the distribution of pathways in coexisting organisms. Consistent with prior findings indicating metabolic handoffs in simple consortia, we find that few organisms within the community can conduct multiple sequential redox transformations. As environmental conditions change, different assemblages of organisms are selected for, altering linkages among the major biogeochemical cycles.
Self-propelling vesicles define glycolysis as the minimal energy machinery for neuronal transport
Authors: Hinckelmann María-Victoria , Virlogeux Amandine , Niehage Christian , Poujol Christel , Choquet Daniel , Hoflack Bernard , Zala Diana , Saudou Frédéric 
Published: October 2016

AbstractThe glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) facilitates fast axonal transport in neurons. However, given that GAPDH does not produce ATP, it is unclear whether glycolysis per se is sufficient to propel vesicles. Although many proteins regulating transport have been identified, the molecular composition of transported vesicles in neurons has yet to be fully elucidated. Here we selectively enrich motile vesicles and perform quantitative proteomic analysis. In addition to the expected molecular motors and vesicular proteins, we find an enrichment of all the glycolytic enzymes. Using biochemical approaches and super-resolution microscopy, we observe that most glycolytic enzymes are selectively associated with vesicles and facilitate transport of vesicles in neurons. Finally, we provide evidence that mouse brain vesicles produce ATP from ADP and glucose, and display movement in a reconstituted in vitro transport assay of native vesicles. We conclude that transport of vesicles along microtubules can be autonomous.
Nitrogen fixation in a chemoautotrophic lucinid symbiosis
Authors: König Sten , Gros Olivier , Heiden Stefan E. , Hinzke Tjorven , Thürmer Andrea , Poehlein Anja , Meyer Susann , Vatin Magalie , Mbéguié-A-Mbéguié Didier , Tocny Jennifer , Ponnudurai Ruby , Daniel Rolf , Becher Dörte , Schweder Thomas , Markert Stephanie 
Published: October 2016

AbstractThe shallow water bivalve Codakia orbicularis lives in symbiotic association with a sulfur-oxidizing bacterium in its gills. The endosymbiont fixes CO2 and thus generates organic carbon compounds, which support the host's growth. To investigate the uncultured symbiont's metabolism and symbiont–host interactions in detail we conducted a proteogenomic analysis of purified bacteria. Unexpectedly, our results reveal a hitherto completely unrecognized feature of the C. orbicularis symbiont's physiology: the symbiont's genome encodes all proteins necessary for biological nitrogen fixation (diazotrophy). Expression of the respective genes under standard ambient conditions was confirmed by proteomics. Nitrogenase activity in the symbiont was also verified by enzyme activity assays. Phylogenetic analysis of the bacterial nitrogenase reductase NifH revealed the symbiont's close relationship to free-living nitrogen-fixing Proteobacteria from the seagrass sediment. The C. orbicularis symbiont, here tentatively named ‘Candidatus Thiodiazotropha endolucinida’, may thus not only sustain the bivalve's carbon demands. C. orbicularis may also benefit from a steady supply of fixed nitrogen from its symbiont—a scenario that is unprecedented in comparable chemoautotrophic symbioses.
Early nucleation events in the polymerization of actin, probed by time-resolved small-angle x-ray scattering
Authors: Oda Toshiro , Aihara Tomoki , Wakabayashi Katsuzo 
Published: October 2016

AbstractNucleators generating new F-actin filaments play important roles in cell activities. Detailed information concerning the events involved in nucleation of actin alone in vitro is fundamental to understanding these processes, but such information has been hard to come by. We addressed the early process of salt-induced polymerization of actin using the time-resolved synchrotron small-angle X-ray scattering (SAXS). Actin molecules in low salt solution maintain a monomeric state by an electrostatic repulsive force between molecules. On mixing with salts, the repulsive force was rapidly screened, causing an immediate formation of many of non-polymerizable dimers. SAXS kinetic analysis revealed that tetramerization gives the highest energetic barrier to further polymerization, and the major nucleation is the formation of helical tetramers. Filaments start to grow rapidly with the formation of pentamers. These findings suggest an acceleration mechanism of actin assembly by a variety of nucleators in cells.
Knowledge-guided fuzzy logic modeling to infer cellular signaling networks from proteomic data
Authors: Liu Hui , Zhang Fan , Mishra Shital Kumar , Zhou Shuigeng , Zheng Jie 
Published: October 2016

AbstractModeling of signaling pathways is crucial for understanding and predicting cellular responses to drug treatments. However, canonical signaling pathways curated from literature are seldom context-specific and thus can hardly predict cell type-specific response to external perturbations; purely data-driven methods also have drawbacks such as limited biological interpretability. Therefore, hybrid methods that can integrate prior knowledge and real data for network inference are highly desirable. In this paper, we propose a knowledge-guided fuzzy logic network model to infer signaling pathways by exploiting both prior knowledge and time-series data. In particular, the dynamic time warping algorithm is employed to measure the goodness of fit between experimental and predicted data, so that our method can model temporally-ordered experimental observations. We evaluated the proposed method on a synthetic dataset and two real phosphoproteomic datasets. The experimental results demonstrate that our model can uncover drug-induced alterations in signaling pathways in cancer cells. Compared with existing hybrid models, our method can model feedback loops so that the dynamical mechanisms of signaling networks can be uncovered from time-series data. By calibrating generic models of signaling pathways against real data, our method supports precise predictions of context-specific anticancer drug effects, which is an important step towards precision medicine.
Velocimetry of superconducting vortices based on stroboscopic resonances
Authors: Jelić Ž. L. , Milošević M. V. , Silhanek A. V. 
Published: October 2016

AbstractAn experimental determination of the mean vortex velocity in superconductors mostly relies on the measurement of flux-flow resistance with magnetic field, temperature, or driving current. In the present work we introduce a method combining conventional transport measurements and a frequency-tuned flashing pinning potential to obtain reliable estimates of the vortex velocity. The proposed device is characterized using the time-dependent Ginzburg-Landau formalism, where the velocimetry method exploits the resonances in mean vortex dissipation when temporal commensuration occurs between the vortex crossings and the flashing potential. We discuss the sensitivity of the proposed technique on applied current, temperature and heat diffusion, as well as the vortex core deformations during fast motion.
A programmable metasurface with dynamic polarization, scattering and focusing control
Authors: Yang Huanhuan , Cao Xiangyu , Yang Fan , Gao Jun , Xu Shenheng , Li Maokun , Chen Xibi , Zhao Yi , Zheng Yuejun , Li Sijia 
Published: October 2016

AbstractDiverse electromagnetic (EM) responses of a programmable metasurface with a relatively large scale have been investigated, where multiple functionalities are obtained on the same surface. The unit cell in the metasurface is integrated with one PIN diode, and thus a binary coded phase is realized for a single polarization. Exploiting this anisotropic characteristic, reconfigurable polarization conversion is presented first. Then the dynamic scattering performance for two kinds of sources, i.e. a plane wave and a point source, is carefully elaborated. To tailor the scattering properties, genetic algorithm, normally based on binary coding, is coupled with the scattering pattern analysis to optimize the coding matrix. Besides, inverse fast Fourier transform (IFFT) technique is also introduced to expedite the optimization process of a large metasurface. Since the coding control of each unit cell allows a local and direct modulation of EM wave, various EM phenomena including anomalous reflection, diffusion, beam steering and beam forming are successfully demonstrated by both simulations and experiments. It is worthwhile to point out that a real-time switch among these functionalities is also achieved by using a field-programmable gate array (FPGA). All the results suggest that the proposed programmable metasurface has great potentials for future applications.
Deep-submicron Graphene Field-Effect Transistors with State-of-Art fmax
Authors: Lyu Hongming , Lu Qi , Liu Jinbiao , Wu Xiaoming , Zhang Jinyu , Li Junfeng , Niu Jiebin , Yu Zhiping , Wu Huaqiang , Qian He 
Published: October 2016

AbstractIn order to conquer the short-channel effects that limit conventional ultra-scale semiconductor devices, two-dimensional materials, as an option of ultimate thin channels, receive wide attention. Graphene, in particular, bears great expectations because of its supreme carrier mobility and saturation velocity. However, its main disadvantage, the lack of bandgap, has not been satisfactorily solved. As a result, maximum oscillation frequency (fmax) which indicates transistors’ power amplification ability has been disappointing. Here, we present submicron field-effect transistors with specially designed low-resistance gate and excellent source/drain contact, and therefore significantly improved fmax. The fabrication was assisted by the advanced 8-inch CMOS back-end-of-line technology. A 200-nm-gate-length GFET achieves fT/fmax = 35.4/50 GHz. All GFET samples with gate lengths ranging from 200 nm to 400 nm possess fmax 31–41% higher than fT, closely resembling Si n-channel MOSFETs at comparable technology nodes. These results re-strengthen the promise of graphene field-effect transistors in next generation semiconductor electronics.
M-DNA/Transition Metal Dichalcogenide Hybrid Structure-based Bio-FET sensor with Ultra-high Sensitivity
Authors: Park Hyung-Youl , Dugasani Sreekantha Reddy , Kang Dong-Ho , Yoo Gwangwe , Kim Jinok , Gnapareddy Bramaramba , Jeon Jaeho , Kim Minwoo , Song Young Jae , Lee Sungjoo , Heo Jonggon , Jeon Young Jin , Park Sung Ha , Park Jin-Hong 
Published: October 2016

AbstractHere, we report a high performance biosensor based on (i) a Cu2+-DNA/MoS2 hybrid structure and (ii) a field effect transistor, which we refer to as a bio-FET, presenting a high sensitivity of 1.7 × 103 A/A. This high sensitivity was achieved by using a DNA nanostructure with copper ions (Cu2+) that induced a positive polarity in the DNA (receptor). This strategy improved the detecting ability for doxorubicin-like molecules (target) that have a negative polarity. Very short distance between the biomolecules and the sensor surface was obtained without using a dielectric layer, contributing to the high sensitivity. We first investigated the effect of doxorubicin on DNA/MoS2 and Cu2+-DNA/MoS2 nanostructures using Raman spectroscopy and Kelvin force probe microscopy. Then, we analyzed the sensing mechanism and performance in DNA/MoS2- and Cu2+-DNA/MoS2-based bio-FETs by electrical measurements (ID-VG at various VD) for various concentrations of doxorubicin. Finally, successful operation of the Cu2+-DNA/MoS2 bio-FET was demonstrated for six cycles (each cycle consisted of four steps: 2 preparation steps, a sensing step, and an erasing step) with different doxorubicin concentrations. The bio-FET showed excellent reusability, which has not been achieved previously in 2D biosensors.
Substitution rate and natural selection in parvovirus B19
Authors: Stamenković Gorana G. , Ćirković Valentina S. , Šiljić Marina M. , Blagojević Jelena V. , Knežević Aleksandra M. , Joksić Ivana D. , Stanojević Maja P. 
Published: October 2016

AbstractThe aim of this study was to estimate substitution rate and imprints of natural selection on parvovirus B19 genotype 1. Studied datasets included 137 near complete coding B19 genomes (positions 665 to 4851) for phylogenetic and substitution rate analysis and 146 and 214 partial genomes for selection analyses in open reading frames ORF1 and ORF2, respectively, collected 1973–2012 and including 9 newly sequenced isolates from Serbia. Phylogenetic clustering assigned majority of studied isolates to G1A. Nucleotide substitution rate for total coding DNA was 1.03 (0.6–1.27) x 10−4 substitutions/site/year, with higher values for analyzed genome partitions. In spite of the highest evolutionary rate, VP2 codons were found to be under purifying selection with rare episodic positive selection, whereas codons under diversifying selection were found in the unique part of VP1, known to contain B19 immune epitopes important in persistent infection. Analyses of overlapping gene regions identified nucleotide positions under opposite selective pressure in different ORFs, suggesting complex evolutionary mechanisms of nucleotide changes in B19 viral genomes.