bluuebunny/crossref_metadata_2025 huggingface dataset:
Sketch-based interaction and modeling: where do we stand?
Authors: Bonnici Alexandra , Akman Alican , Calleja Gabriel , Camilleri Kenneth P. , Fehling Patrick , Ferreira Alfredo , Hermuth Florian , Israel Johann Habakuk , Landwehr Tom , Liu Juncheng , Padfield Natasha M. J. , Sezgin T. Metin , Rosin Paul L.
Published: November 2019

Sketching is a natural and intuitive communication tool used for expressing concepts or ideas which are difficult to communicate through text or speech alone. Sketching is therefore used for a variety of purposes, from the expression of ideas on two-dimensional (2D) physical media, to object creation, manipulation, or deformation in three-dimensional (3D) immersive environments. This variety in sketching activities brings about a range of technologies which, while having similar scope, namely that of recording and interpreting the sketch gesture to effect some interaction, adopt different interpretation approaches according to the environment in which the sketch is drawn. In fields such as product design, sketches are drawn at various stages of the design process, and therefore, designers would benefit from sketch interpretation technologies which support these differing interactions. However, research typically focuses on one aspect of sketch interpretation and modeling such that literature on available technologies is fragmented and dispersed. In this paper, we bring together the relevant literature describing technologies which can support the product design industry, namely technologies which support the interpretation of sketches drawn on 2D media, sketch-based search interactions, as well as sketch gestures drawn in 3D media. This paper, therefore, gives a holistic view of the algorithmic support that can be provided in the design process. In so doing, we highlight the research gaps and future research directions required to provide full sketch-based interaction support.
Subglacial topography and thickness of ice caps on the Argentine Islands
Authors: Karušs Jānis , Lamsters Kristaps , Chernov Anatolii , Krievāns Māris , Ješkins Jurijs
Published: November 2019

This study presents the first subglacial topography and ice thickness models of the largest ice caps of the Argentine Islands, Wilhelm Archipelago, West Antarctica. During this study, ground-penetrating radar was used to map the thickness and inner structure of the ice caps. Digital surface models of all studied islands were created from aerial images obtained with a small-sized unmanned aerial vehicle and used for the construction of subglacial topography models. Ice caps of the Argentine Islands cover ~50% of the land surface of the islands on average. The maximum thickness of only two islands (Galindez and Skua) exceeds 30 m, while the average thickness of all islands is only ~5 m. The maximum ice thickness reaches 35.3 m on Galindez Island. The ice thickness and glacier distribution are mainly governed by prevailing wind direction from the north. This has created the prominent narrow ice ridges on Uruguay and Irizar islands, which are not supported by topographic obstacles, as well as the elongated shape of other ice caps. The subglacial topography of the ice caps is undulated and mainly dependent on the geological structure and composition of magmatic rocks.
Working with Electroacoustic Music in Rural Communities: The use of an interactive music system in the creative process in primary and secondary school education
Authors: Duarte-García Mario Alberto , Sigal-Sefchovich Jorge Rodrigo
Published: November 2019

This article describes a project intended to promote access to electroacoustic music for children and teenagers aged 6 to 15 years in a socially and educationally disadvantaged rural community in Michoacán, Mexico. It explores an educational model of teaching, learning and creation of electroacoustic music through the use of music technology and pedagogy based on constructivism and Paulo Freire’s ideas on education as a practice of freedom. It provides a pedagogical reflection on the processes of learning and appreciation of this new music. The project includes the use of an interactive music system – implemented in MaxMSP using a mobile phone OSC app to control space and its interaction with timbre, pitch and duration – as an aid in the classroom and its implementation in an educational programme with a social impact. The research covered in this article could be taken into account to deliver new music education in rural communities with similar socioeconomic circumstances.
Activating Audiences: How spatial music can help us to listen
Authors: Matthews Emma-Kate
Published: November 2019

This article discusses the importance of active listening when engaging new audiences with experimental and unfamiliar musical formats. Spatial music is examined as a physically immersive medium in which the audience is implicated as an active component in the execution of its performance. A brief account of the historic context of spatial music will be presented alongside speculation for the trajectory of its future; particularly its potential as a model for audience engagement. This article will first consider how spatially immersive performances have the capacity to activate listeners and how can this help to engage new audiences with new ways of listening. It will also question the notion of inhabiting spatial music, with an investigation of the multiple ways in which spatial music relates to physical space and the terms of its inhabitation. The concept of virtual listening will be discussed in response to trends towards passive hearing, as driven by recent technological developments in acoustic software and hardware, and the resultant abstraction of the spatial and social dynamics of sound in virtual space. The physiological and psychological differences between listening and hearing will also be examined as a means of establishing fundamental differences in the ways that we interact with music, and questioning what our listening habits tell us about audience engagement in the context of experimental music performance. This article will also question the individual roles of the musician, composer, architect/designer and audience in the ongoing responsibility to improve audience engagement in new, or unfamiliar musical works. Importantly, this article will also explicitly examine who we are referring to when we use the term ‘new audiences’. Major developments in acoustic technology during the last few decades have somewhat confused the diagram between music, space and listener. The understanding of which elements are active and which are passive is especially ambiguous at a time when ambisonic and binaural technologies have become developed enough to provide accurate simulations of the abstract, acoustic qualities of spaces, but on virtual terms. Architects, composers, musicians, engineers and audiences are at a crossroads in the development of new music and experimental, spatiosonic practice. ‘Spatiosonic’ is a hybrid term which is used throughout this article to describe work and phenomena which regard space (spatio) and sound (sonic) as equal, interactive partners. This article considers some of the opportunities and limitations at stake in current techniques of composition, performance and listening.
A Consideration of the Code of Computer Music as Writing, and Some Thinking on Analytical Theories
Authors: Larrieu Maxence
Published: November 2019

This article focuses on the analysis of computer music, that is, music which uses programming languages so that what the listener hears is the result of computer code. One key point in this article is that this music exists with some writing, that is, the computer code. I note that this key point has not been addressed in the latest theories for analysing computer music. Indeed, we often see this music as part of the electroacoustic field, where theaudio signalis essential, and where we usually read that those musics arenon-writtenmusic. After an introduction on this topic, in the second section I will make a distinction between ‘before the signal’ and ‘from the signal’ to organise the theories to analyse electroacoustic music. In the third section, I will focus on computer music and I will show the historical difficulty in considering ‘code’ in musical analysis, mainly with an important exchange between two pioneers, Marco Stroppa and Jean-Claude Risset. In the fourth section I will explain with Jean-Claude Risset and Horacio Vaggione the specificity of computer music: this music is written. Finally, I will look into a recent analysis theory, theInteractive Aural Analysisby Michael Clarke, which seems to fit with the latter specificity.
RISK SHOCKS, RISK MANAGEMENT, AND INVESTMENT
Authors: Goldberg Jonathan
Published: November 2019

This paper studies the macroeconomic effects of shocks to idiosyncratic business risk in an economy with endogenously incomplete markets. I develop a model in which firms face idiosyncratic risk and obtain insurance from intermediaries through contracts akin to credit lines. Insurance is imperfect due to limited commitment in financial contracts. Although steady-state capital is higher than if firms were constrained to issue only standard equity, a rise in uncertainty about idiosyncratic business outcomes leads to an endogenous reduction in risk sharing. This deterioration in risk sharing results from a general-equilibrium shortage of pledgeable assets and implies that the economy’s response to an increase in idiosyncratic business risk can be amplified by financial contracting rather than dampened. In a parametrized version of the model, a rise in idiosyncratic business risk generates a large increase in uncertainty about aggregate investment.
Rethinking climate policy with alternative framings of carbon dioxide
Authors: Levänen Jarkko , Hukkinen Janne I.
Published: November 2019

Since the earliest stages of international climate policy, carbon dioxide (CO2) has been framed and widely accepted as a problem that needs to be solved by reducing its amount in the atmosphere. In principle this is a correct and relevant starting point for efforts to decarbonize societies. At the same time, however, the unquestioned and one-sided framing of CO2 as a problem has significantly biased the strategies for tackling climate change. We introduce the origins, meanings and implications of one-sided framing of CO2 in climate policy. We also discuss how alternative framings could impact policymaking and eventually our capacity to mitigate climate change. We introduce a paradox: framing CO2 as a problem often translates into policies that hamper the implementation of technologies to decrease the amount of CO2 emitted into the atmosphere. We suggest that plurality in framing CO2 could lead to innovative ways and strategies to combat climate change.
Water Mass Characteristics of the Antarctic Margins and the Production and Seasonality of Dense Shelf Water
Authors: Narayanan Aditya , Gille Sarah T. , Mazloff Matthew R. , Murali K.
Published: November 2019

Conductivity‐temperature‐depth data from instrumented seals of the Marine Mammals Exploring Oceans from Pole to Pole program are analyzed to characterize the water masses and the seasonality of the marginal seas. Bottom temperatures are found to be in a cold regime in Dense Shelf Water (DSW) producing regions, identified in this study as the southern Weddell Sea, Cape Darnley, Prydz Bay, Adélie Coast, and the western Ross Sea. DSW occupies the bottom of the Weddell and Ross Sea continental shelves throughout the year: Production of DSW and vertical overturning occur only during the winter. In the other DSW producing regions, salinity is reduced more markedly during the summer. We identify the Princess Martha Coast, Leopold and Astrid Coast, and the Knox Coast as Low Salinity Shelf Water producing regions, where modified Circumpolar Deep Water (CDW) intrudes onto the continental shelf, reaching areas close to the ice shelves keeping the bottom temperatures in an intermediate regime. The Prince Harald Coast, the Amundsen Sea, and the Bellingshausen Sea experience more intense CDW intrusion, which keeps them in a warm regime year‐round. CDW layer thicknesses correlate with the meridional winds over the shelf sea, and with the zonal winds at the slope, while DSW layer thicknesses correlate with the meridional winds over the shelf seas and the curl of the wind stress over the slope. Locations of DSW on the continental shelf coincide with an absence of warmer CDW near the ice shelves.
Nonlinear Dynamics in Treatment Wetlands: Identifying Systematic Drivers of Nonequilibrium Outlet Concentrations in Everglades STAs
Authors: Medina Miles , Huffaker Ray , Jawitz James W. , Muñoz‐Carpena Rafael
Published: November 2019

Constructed treatment wetlands intercept nutrients in surface runoff to protect downstream ecosystems. Conventionally, nutrient removal is considered from a chemical kinetics perspective that assumes outlet concentrations tend toward equilibrium. We propose a broader view that includes management intervention as part of the system, and we explore the possibility that complex concentration dynamics emerge endogenously from nonlinear interactions. In particular, through application of a novel nonlinear time series diagnostic framework, we empirically test whether phosphorus removal at two Stormwater Treatment Areas (STAs) in South Florida might be enhanced through improved management of hydraulic and phosphorus loads. We isolated low‐dimensional, deterministic signals in STA input/output dynamics (flows and total phosphorus concentrations); mapped causal interactions among covariates; and developed parsimonious data‐driven dynamic models to simulate and characterize key interactions. At STA‐3/4, inflow dynamics systematically drove outlet concentrations, suggesting that outlet concentration variability might be reduced through enhanced hydraulic load management. We also detected management feedback in the reverse direction—STA‐3/4 outlet concentrations driving inflows—and identified a possible inefficiency in this management response. At STA‐2, neither flows nor inlet concentrations systematically drove outlet concentrations, suggesting that the wetland effectively removed incoming load signals. However, STA‐2 inflows were evidently influenced by inlet concentrations (management feedback). The differing management feedback structures between STAs suggest that STA‐3/4 performance might be improved by managing hydraulic loads more strongly in response to inlet concentrations. More broadly, this work demonstrates that management‐relevant insights into dynamic cause‐and‐effect relationships can be gleaned from observed treatment dynamics.
Favorable Conditions for Suspension Freezing in an Arctic Coastal Polynya
Authors: Ito Masato , Ohshima Kay I. , Fukamachi Yasushi , Hirano Daisuke , Mahoney Andrew R. , Jones Joshua , Takatsuka Toru , Eicken Hajo
Published: November 2019

Arctic sea ice incorporates and transports sediment, releasing it back into the water column during the melting season. This process constitutes an important aspect of marine sediment transport and biogeochemical cycling. Sediment incorporation into sea ice is considered to occur mainly through underwater interaction between frazil ice and resuspended sediment, referred to as suspension freezing. However, harsh environmental conditions have greatly limited field observations of this phenomenon. Analysis of mooring data from a coastal polynya in the northeastern Chukchi Sea, in conjunction with coastal ice radar and meteorological data, indicates that suspension freezing is a key mechanism for sediment entrainment into sea ice. During polynya episodes, acoustic backscatter data obtained by an Acoustic Doppler Current Profiler showed the presence of frazil ice from the surface down to 20‐ to 25‐m depth, coinciding with in situ and potential supercooling. Underwater frazil ice persisted over 1 week under windy, turbulent water column conditions. A combination of the turbidity and Acoustic Doppler Current Profiler backscatter data revealed upward sediment dispersion associated with strong currents during the polynya episodes. The fact that frazil ice and resuspended sediment were detected at the same depth and time strongly suggests the interaction between ice crystals and sediment particles, that is, suspension freezing.
Subseasonal Forecasts of the 2018 Indian Summer Monsoon Over Bihar
Authors: Robertson Andrew W. , Acharya Nachiketa , Goddard Lisa , Pattanaik D. R. , Sahai A. K. , Singh K. K. , Ghosh Kripan , Agarwal Anshul , Buizer James L.
Published: November 2019

Calibrated probabilistic forecasts of weekly rainfall were developed for the state of Bihar in northern India and issued in real time during the June–September 2018 monsoon period, up to 2 weeks in advance. The forecasts are based on subseasonal forecasts from the U.S. National Centers for Environmental Prediction CFSv2 model and were calibrated against observed gridded rainfall fields from the India Meteorological Department using canonical correlation analysis. Hindcasts over the 1999–2010 period exhibit appreciable skill at Week 1 lead (Days 3–9), with some skill at Week 2 (Days 10–16), over Bihar as well as over a larger region. Forecasts were issued in real time during the 2018 Indian summer monsoon season for four districts in Bihar on a 1° grid in tercile probability format every Thursday. Verification of the district‐level real‐time forecasts over the 2018 season is evaluated and moderate skill demonstrated in terms of the Brier and Heidke skill scores, especially for the northern districts and for the below‐normal category. Successful monsoon onset and break phase forecasts in 2018 over Bihar are related to episodes of the Madden‐Julian Oscillation, which the model is shown to capture quite well at 1–2 week lead.
Understanding Bulk Sediment Stable Isotope Records in the Eastern Equatorial Pacific, From Seven Million Years Ago to Present Day
Authors: Reghellin Daniele , Dickens Gerald R. , Coxall Helen K. , Backman Jan
Published: November 2019

Stable isotope (δ13C and δ18O) records of bulk marine sediment carry information on past carbon cycling and oceanography, but origins and interpretations remain uncertain because such signals represent mixtures of different biogenic components, each with potential offsets from primary parameters. Studies of Neogene sediment from the eastern equatorial Pacific (EEP) exemplify this issue, because stable isotope records of bulk sediment and foraminifera at different sites exhibit similarities and differences in absolute value that somehow relate to depositional age. Here we measure δ13C and δ18O of bulk carbonate, two fine‐grained fractions (<63 and <20 μm), mixed‐species planktic and benthic foraminifera, and foraminifera fragments from sediments deposited over four time intervals within the last 7 Ma at ODP Site 851. These data are compared to published δ13C and δ18O records of multiple single‐species planktic foraminifera from the same site and benthic foraminifera from an adjacent site. Bulk sediment δ13C and δ18O records represent a mixed signal dominated by reticulofenestrid coccolith calcite but modified by variable amounts of different foraminifera. Similarities and differences between stable isotope records result from temporal changes in water chemistry and temperature, depths of calcite precipitation, and vital effects that impact fractionation of various biogenic components. The remarkable correlation of bulk stable isotope records within the EEP suggests that several factors change collectively over time across a broad oceanographic region. Ideally, multiple stable isotope records coupled with other proxy measurements might lead to an internally consistent paleoceanographic perspective of the EEP since the late Miocene.
Branched-chain amino acids sustain pancreatic cancer growth by regulating lipid metabolism
Authors: Lee Ji Hyeon , Cho Young-ra , Kim Ji Hye , Kim Jongwook , Nam Hae Yun , Kim Seong Who , Son Jaekyoung
Published: November 2019

Branched-chain amino acid (BCAA) catabolism and high levels of enzymes in the BCAA metabolic pathway have recently been shown to be associated with cancer growth and survival. However, the precise roles of BCAA metabolism in cancer growth and survival remain largely unclear. Here, we found that BCAA metabolism has an important role in human pancreatic ductal adenocarcinoma (PDAC) growth by regulating lipogenesis. Compared with nontransformed human pancreatic ductal (HPDE) cells, PDAC cells exhibited significantly elevated BCAA uptake through solute carrier transporters, which were highly upregulated in pancreatic tumor tissues compared with normal tissues. Branched-chain amino-acid transaminase 2 (BCAT2) knockdown markedly impaired PDAC cell proliferation, but not HPDE cell proliferation, without significant alterations in glutamate or reactive oxygen species levels. Furthermore, PDAC cell proliferation, but not HPDE cell proliferation, was substantially inhibited upon knockdown of branched-chain α-keto acid dehydrogenase a (BCKDHA). Interestingly, BCKDHA knockdown had no significant effect on mitochondrial metabolism; that is, neither the level of tricarboxylic acid cycle intermediates nor the oxygen consumption rate was affected. However, BCKDHA knockdown significantly inhibited fatty-acid synthesis, indicating that PDAC cells may utilize BCAAs as a carbon source for fatty-acid biosynthesis. Overall, our findings show that the BCAA metabolic pathway may provide a novel therapeutic target for pancreatic cancer.
Adaptive optics in laser processing
Authors: Salter Patrick S. , Booth Martin J.
Published: November 2019

Adaptive optics are becoming a valuable tool for laser processing, providing enhanced functionality and flexibility for a range of systems. Using a single adaptive element, it is possible to correct for aberrations introduced when focusing inside the workpiece, tailor the focal intensity distribution for the particular fabrication task and/or provide parallelisation to reduce processing times. This is particularly promising for applications using ultrafast lasers for three-dimensional fabrication. We review recent developments in adaptive laser processing, including methods and applications, before discussing prospects for the future.
PCDH17 increases the sensitivity of colorectal cancer to 5-fluorouracil treatment by inducing apoptosis and autophagic cell death
Authors: Liu Shuiping , Lin Haoming , Wang Da , Li Qiang , Luo Hong , Li Guoxiong , Chen Xiaohui , Li Yongqiang , Chen Peng , Zhai Bingtao , Wang Wengang , Zhang Ruonan , Chen Bi , Zhang Mingming , Han Xuemeng , Li Qiujie , Chen Liuxi , Liu Ying , Chen Xiaying , Li Guohua , Xiang Yu , Duan Ting , Feng Jiao , Lou Jianshu , Huang Xingxing , Zhang Qin , Pan Ting , Yan Lili , Jin Ting , Zhang Wenzheng , Zhuo Lvjia , Sun Yitian , Xie Tian , Sui Xinbing
Published: November 2019

5-Fluorouracil (5-FU) is known as a first-line chemotherapeutic agent against colorectal cancer (CRC), but drug resistance occurs frequently and significantly limits its clinical success. Our previous study showed that the protocadherin 17 (PCDH17) gene was frequently methylated and functioned as a tumor suppressor in CRC. However, the relationship between PCDH17 and 5-FU resistance in CRC remains unclear. Here, we revealed that PCDH17 was more highly expressed in 5-FU-sensitive CRC tissues than in 5-FU-resistant CRC tissues, and high expression of PCDH17 was correlated with high BECN1 expression. Moreover, this expression profile contributed to superior prognosis and increased survival in CRC patients. Restoring PCDH17 expression augmented the 5-FU sensitivity of CRC in vitro and in vivo by promoting apoptosis and autophagic cell death. Furthermore, autophagy played a dominant role in PCDH17-induced cell death, as an autophagy inhibitor blocked cell death to a greater extent than the pancaspase inhibitor Z-VAD-FMK. PCDH17 inhibition by siRNA decreased the autophagy response and 5-FU sensitivity. Mechanistically, we showed that c-Jun NH2-terminal kinase (JNK) activation was a key determinant in PCDH17-induced autophagy. The compound SP600125, an inhibitor of JNK, suppressed autophagy and 5-FU-induced cell death in PCDH17-reexpressing CRC cells. Taken together, our findings suggest for the first time that PCDH17 increases the sensitivity of CRC to 5-FU treatment by inducing apoptosis and JNK-dependent autophagic cell death. PCDH17 may be a potential prognostic marker for predicting 5-FU sensitivity in CRC patients.
Clinical relevance of TP53 hotspot mutations in high-grade serous ovarian cancers
Authors: Tuna Musaffe , Ju Zhenlin , Yoshihara Kosuke , Amos Christopher I. , Tanyi Janos L. , Mills Gordon B.
Published: November 2019

Background

Mutation ofTP53is the most frequent genetic alteration in high-grade serous ovarian cancer (HGSOC). The impact of hotspot mutations ofTP53and protein levels on patient outcomes in HGSOC has not been fully elucidated.

Methods

The study population (n = 791) comprised of HGSOC samples withTP53mutation from TCGA and other publicly available data. Univariate and multivariate cox proportional hazards regression analyses were used to select variables that were correlated with patient survival.

Results

We assessed the effects ofTP53mutations based on type and individual hotspot mutations on patient outcomes in HGSOC. Only hotspot mutations were associated with outcomes. Three hotspot mutations: G266, Y163C, and R282, in aggregate were associated with a worsened overall and recurrence-free survival compared with other hotspot mutations (p < 0.0001 andp = 0.001), other non-hotspot missense mutations (p < 0.0001 andp = 0.008), truncated mutations (p < 0.0001 andp = 0.001), and all other mutations (p < 0.0001 andp = 0.001). Specific hotspot mutations were associated with different protein expression patterns consistent with different functions.

Conclusions

This study provides evidence that individualTP53hotspot mutations have different impact on HGSOC patient outcomes and potentially TP53 function. Thus the status of particularTP53aberrations could influence response to therapy and selection of therapeutic agents.
Rebound of shelf water salinity in the Ross Sea
Authors: Castagno Pasquale , Capozzi Vincenzo , DiTullio Giacomo R. , Falco Pierpaolo , Fusco Giannetta , Rintoul Stephen R. , Spezie Giancarlo , Budillon Giorgio
Published: November 2019

Antarctic Bottom Water (AABW) supplies the lower limb of the global overturning circulation and ventilates the abyssal ocean. In recent decades, AABW has warmed, freshened and reduced in volume. Ross Sea Bottom Water (RSBW), the second largest source of AABW, has experienced the largest freshening. Here we use 23 years of summer measurements to document temporal variability in the salinity of the Ross Sea High Salinity Shelf Water (HSSW), a precursor to RSBW. HSSW salinity decreased between 1995 and 2014, consistent with freshening observed between 1958 and 2008. However, HSSW salinity rebounded sharply after 2014, with values in 2018 similar to those observed in the mid-late 1990s. Near-synchronous interannual fluctuations in salinity observed at five locations on the continental shelf suggest that upstream preconditioning and large-scale forcing influence HSSW salinity. The rate, magnitude and duration of the recent salinity increase are unusual in the context of the (sparse) observational record.
Enhanced lysosomal degradation maintains the quiescent state of neural stem cells
Authors: Kobayashi Taeko , Piao Wenhui , Takamura Toshiya , Kori Hiroshi , Miyachi Hitoshi , Kitano Satsuki , Iwamoto Yumiko , Yamada Mayumi , Imayoshi Itaru , Shioda Seiji , Ballabio Andrea , Kageyama Ryoichiro
Published: November 2019

Quiescence is important for sustaining neural stem cells (NSCs) in the adult brain over the lifespan. Lysosomes are digestive organelles that degrade membrane receptors after they undergo endolysosomal membrane trafficking. Enlarged lysosomes are present in quiescent NSCs (qNSCs) in the subventricular zone of the mouse brain, but it remains largely unknown how lysosomal function is involved in the quiescence. Here we show that qNSCs exhibit higher lysosomal activity and degrade activated EGF receptor by endolysosomal degradation more rapidly than proliferating NSCs. Chemical inhibition of lysosomal degradation in qNSCs prevents degradation of signaling receptors resulting in exit from quiescence. Furthermore, conditional knockout of TFEB, a lysosomal master regulator, delays NSCs quiescence in vitro and increases NSC proliferation in the dentate gyrus of mice. Taken together, our results demonstrate that enhanced lysosomal degradation is an important regulator of qNSC maintenance.
Glycogen branching enzyme controls cellular iron homeostasis via Iron Regulatory Protein 1 and mitoNEET
Authors: Huynh Nhan , Ou Qiuxiang , Cox Pendleton , Lill Roland , King-Jones Kirst
Published: November 2019

Iron Regulatory Protein 1 (IRP1) is a bifunctional cytosolic iron sensor. When iron levels are normal, IRP1 harbours an iron-sulphur cluster (holo-IRP1), an enzyme with aconitase activity. When iron levels fall, IRP1 loses the cluster (apo-IRP1) and binds to iron-responsive elements (IREs) in messenger RNAs (mRNAs) encoding proteins involved in cellular iron uptake, distribution, and storage. Here we show that mutations in the Drosophila 1,4-Alpha-Glucan Branching Enzyme (AGBE) gene cause porphyria. AGBE was hitherto only linked to glycogen metabolism and a fatal human disorder known as glycogen storage disease type IV. AGBE binds specifically to holo-IRP1 and to mitoNEET, a protein capable of repairing IRP1 iron-sulphur clusters. This interaction ensures nuclear translocation of holo-IRP1 and downregulation of iron-dependent processes, demonstrating that holo-IRP1 functions not just as an aconitase, but throttles target gene expression in anticipation of declining iron requirements.
Room-temperature quantum interference in single perovskite quantum dot junctions
Authors: Zheng Haining , Hou Songjun , Xin Chenguang , Wu Qingqing , Jiang Feng , Tan Zhibing , Zhou Xin , Lin Luchun , He Wenxiang , Li Qingmin , Zheng Jueting , Zhang Longyi , Liu Junyang , Yang Yang , Shi Jia , Zhang Xiaodan , Zhao Ying , Li Yuelong , Lambert Colin , Hong Wenjing
Published: November 2019

The studies of quantum interference effects through bulk perovskite materials at the Ångstrom scale still remain as a major challenge. Herein, we provide the observation of room-temperature quantum interference effects in metal halide perovskite quantum dots (QDs) using the mechanically controllable break junction technique. Single-QD conductance measurements reveal that there are multiple conductance peaks for the CH3NH3PbBr3 and CH3NH3PbBr2.15Cl0.85 QDs, whose displacement distributions match the lattice constant of QDs, suggesting that the gold electrodes slide through different lattice sites of the QD via Au-halogen coupling. We also observe a distinct conductance ‘jump’ at the end of the sliding process, which is further evidence that quantum interference effects dominate charge transport in these single-QD junctions. This conductance ‘jump’ is also confirmed by our theoretical calculations utilizing density functional theory combined with quantum transport theory. Our measurements and theory create a pathway to exploit quantum interference effects in quantum-controlled perovskite materials.
CRISPR-Switch regulates sgRNA activity by Cre recombination for sequential editing of two loci
Authors: Chylinski Krzysztof , Hubmann Maria , Hanna Ruth E. , Yanchus Connor , Michlits Georg , Uijttewaal Esther C. H. , Doench John , Schramek Daniel , Elling Ulrich
Published: November 2019

CRISPR-Cas9 is an efficient and versatile tool for genome engineering in many species. However, inducible CRISPR-Cas9 editing systems that regulate Cas9 activity or sgRNA expression often suffer from significant limitations, including reduced editing capacity, off-target effects, or leaky expression. Here, we develop a precisely controlled sgRNA expression cassette that can be combined with widely-used Cre systems, termed CRISPR-Switch (SgRNA With Induction/Termination by Cre Homologous recombination). Switch-ON facilitates controlled, rapid induction of sgRNA activity. In turn, Switch-OFF-mediated termination of editing improves generation of heterozygous genotypes and can limit off-target effects. Furthermore, we design sequential CRISPR-Switch-based editing of two loci in a strictly programmable manner and determined the order of mutagenic events that leads to development of glioblastoma in mice. Thus, CRISPR-Switch substantially increases the versatility of gene editing through precise and rapid switching ON or OFF sgRNA activity, as well as switching OVER to secondary sgRNAs.
Biofilms facilitate cheating and social exploitation of β-lactam resistance in Escherichia coli
Authors: Amanatidou Elli , Matthews Andrew C. , Kuhlicke Ute , Neu Thomas R. , McEvoy James P. , Raymond Ben
Published: November 2019

Gram-negative bacteria such as Escherichia coli commonly resist β-lactam antibiotics using plasmid-encoded β-lactamase enzymes. Bacterial strains that express β-lactamases have been found to detoxify liquid cultures and thus to protect genetically susceptible strains, constituting a clear laboratory example of social protection. These results are not necessarily general; on solid media, for instance, the rapid bactericidal action of β-lactams largely prevents social protection. Here, we tested the hypothesis that the greater tolerance of biofilm bacteria for β-lactams would facilitate social interactions. We used a recently isolated E. coli strain, capable of strong biofilm formation, to compare how cooperation and exploitation in colony biofilms and broth culture drives the dynamics of a non-conjugative plasmid encoding a clinically important β-lactamase. Susceptible cells in biofilms were tolerant of ampicillin—high doses and several days of exposure were required to kill them. In support of our hypothesis, we found robust social protection of susceptible E. coli in biofilms, despite fine-scale physical separation of resistant and susceptible cells and lower rates of production of extracellular β-lactamase. In contrast, social interactions in broth were restricted to a relatively narrow range of ampicillin doses. Our results show that β-lactam selection pressure on Gram-negative biofilms leads to cooperative resistance characterized by a low equilibrium frequency of resistance plasmids, sufficient to protect all cells.
Systematic beyond-DFT study of binary transition metal oxides
Authors: Mandal Subhasish , Haule Kristjan , Rabe Karin M. , Vanderbilt David
Published: November 2019

Various methods going beyond density functional theory (DFT), such as DFT+U, hybrid functionals, meta-GGAs, GW, and DFT-embedded dynamical mean field theory (eDMFT), have been developed to describe the electronic structure of correlated materials, but it is unclear how accurate these methods can be expected to be when applied to a given strongly correlated solid. It is thus of pressing interest to compare their accuracy as they apply to different categories of materials. Here we introduce a novel paradigm in which a chosen set of beyond-DFT methods is systematically and uniformly tested on a chosen class of materials. For a first application, we choose the target materials to be the binary transition metal oxides FeO, CoO, MnO, and NiO in their antiferromagnetic phase and present a head-to-head comparison of spectral properties as computed using the various methods. We also compare with available experimental angle-resolved photoemission spectroscopy (ARPES), inverse-photoemission spectroscopy, and with optical absorption. For the class of compounds studied here, we find that both B3LYP and eDMFT reproduce the experiments quite well, with eDMFT doing best, in particular when comparing with the ARPES data.
Acute levodopa dosing around-the-clock ameliorates REM sleep without atonia in hemiparkinsonian rats
Authors: Iyer Vishakh , Vo Quynh , Mell Anthony , Chinniah Siven , Zenerovitz Ashley , Venkiteswaran Kala , Kunselman Allen R. , Fang Jidong , Subramanian Thyagarajan
Published: November 2019

Rapid-eye-movement (REM) sleep without atonia (RSWA), a marker of REM sleep behavior disorder (RBD), is frequently comorbid with Parkinson’s disease (PD). Although rodent models are commonly used for studying PD, the neurobiological and behavioral correlates of RBD remain poorly understood. Therefore, we developed a behavior-based criteria to identify RSWA in the hemiparkinsonian rat model of PD. Video recordings of rats were analyzed, to develop a criteria consisting of behavioral signs that occurred during polysomnographically confirmed epochs of sleep-wake stages. The sleep-slouch, a postural shift of the body or head caused only by gravity, was identified as a unique behavioral sign of REM sleep onset and was altered in hemiparkinsonian rats during RSWA. There was a significant correlation between the behavior-based criteria and polysomnograms for all sleep-wake stages in control but not hemiparkinsonian rats indicating a deterioration of sleep-wake architecture in parkinsonism. We then tested the efficacy of levodopa in ameliorating RSWA using intermittent and around-the-clock (ATC) dosing regimens. ATC levodopa dosing at 4 mg/kg for 48 h caused a significant reduction of RSWA as measured by polysomnography and the behavioral-based criteria along with an amelioration of forelimb motor deficits. Our findings show that the phenomenological correlates of RSWA can be reliably characterized in the hemiparkinsonian rat model. ATC levodopa administration ameliorates RSWA in this model without deleterious consequences to the overall sleep-wake architecture and therapeutic benefits for parkinsonian motor deficits. These findings suggest that further study may allow for the application of a similar approach to treat RBD in PD patients.
Local-measurement-based quantum state tomography via neural networks
Authors: Xin Tao , Lu Sirui , Cao Ningping , Anikeeva Galit , Lu Dawei , Li Jun , Long Guilu , Zeng Bei
Published: November 2019

Quantum state tomography is a daunting challenge of experimental quantum computing, even in moderate system size. One way to boost the efficiency of state tomography is via local measurements on reduced density matrices, but the reconstruction of the full state thereafter is hard. Here, we present a machine-learning method to recover the ground states of $$k$$k-local Hamiltonians from just the local information, where a fully connected neural network is built to fulfill the task with up to seven qubits. In particular, we test the neural network model with a practical dataset, that in a 4-qubit nuclear magnetic resonance system our method yields global states via the 2-local information with high accuracy. Our work paves the way towards scalable state tomography in large quantum systems.
A global wildfire dataset for the analysis of fire regimes and fire behaviour
Authors: Artés Tomàs , Oom Duarte , de Rigo Daniele , Durrant Tracy Houston , Maianti Pieralberto , Libertà Giorgio , San-Miguel-Ayanz Jesús
Published: November 2019

Global fire monitoring systems are crucial to study fire behaviour, fire regimes and their impact at the global scale. Although global fire products based on the use of Earth Observation satellites exist, most remote sensing products only partially cover the requirements for these analyses. These data do not provide information like fire size, fire spread speed, how fires may evolve and joint into single event, or the number of fire events for a given area. This high level of abstraction is very valuable; it makes it possible to characterize fires by types (either size, spread, behaviour, etc.). Here, we present and test a data mining work flow to create a global database of single fires that allows for the characterization of fire types and fire regimes worldwide. This work describes the data produced by a data mining process using MODIS burnt area product Collection 6 (MCD64A1). The entire product has been computed until the present and is available under the umbrella of the Global Wildfire Information System (GWIS).
Quantitative firing pattern phenotyping of hippocampal neuron types
Authors: Komendantov Alexander O. , Venkadesh Siva , Rees Christopher L. , Wheeler Diek W. , Hamilton David J. , Ascoli Giorgio A.
Published: November 2019

Systematically organizing the anatomical, molecular, and physiological properties of cortical neurons is important for understanding their computational functions. Hippocampome.org defines 122 neuron types in the rodent hippocampal formation based on their somatic, axonal, and dendritic locations, putative excitatory/inhibitory outputs, molecular marker expression, and biophysical properties. We augmented the electrophysiological data of this knowledge base by collecting, quantifying, and analyzing the firing responses to depolarizing current injections for every hippocampal neuron type from published experiments. We designed and implemented objective protocols to classify firing patterns based on 5 transients (delay, adapting spiking, rapidly adapting spiking, transient stuttering, and transient slow-wave bursting) and 4 steady states (non-adapting spiking, persistent stuttering, persistent slow-wave bursting, and silence). This automated approach revealed 9 unique (plus one spurious) families of firing pattern phenotypes while distinguishing potential new neuronal subtypes. Novel statistical associations emerged between firing responses and other electrophysiological properties, morphological features, and molecular marker expression. The firing pattern parameters, experimental conditions, spike times, references to the original empirical evidences, and analysis scripts are released open-source through Hippocampome.org for all neuron types, greatly enhancing the existing search and browse capabilities. This information, collated online in human- and machine-accessible form, will help design and interpret both experiments and model simulations.
Translocation through a narrow pore under a pulling force
Authors: Niknam Hamidabad Mohammadreza , Haji Abdolvahab Rouhollah
Published: November 2019

We employ a three-dimensional molecular dynamics to simulate a driven polymer translocation through a nanopore by applying an external force, for four pore diameters and two external forces. To see the polymer and pore interaction effects on translocation time, we studied nine interaction energies. Moreover, to better understand the simulation results, we investigate polymer center of mass, shape factor and the monomer spatial distribution through the translocation process. Our results reveal that increasing the polymer-pore interaction energy is accompanied by an increase in the translocation time and decrease in the process rate. Furthermore, for pores with greater diameter, the translocation becomes faster. The shape analysis of the polymer indicates that the polymer shape is highly sensitive to the interaction energy. In great interactions, the monomers come close to the pore from both sides. As a result, the translocation becomes fast at first and slows down at last. Overall, it can be concluded that the external force does not play a major role in the shape and distribution of translocated monomers. However, the interaction energy between monomer and nanopore has a major effect especially on the distribution of translocated monomers on the trans side.
Maturing global CO2 storage resources on offshore continental margins to achieve 2DS emissions reductions
Authors: Ringrose P. S. , Meckel T. A.
Published: November 2019

Most studies on CO2 emissions reduction strategies that address the ‘two-degree scenario’ (2DS) recognize a significant role for CCS. For CCS to be effective, it must be deployed globally on both existing and emerging energy systems. For nations with large-scale emissions, offshore geologic CO2 storage provides an attractive and efficient long-term strategy. While some nations are already developing CCS projects using offshore CO2 storage resources, most geographic regions have yet to begin. This paper demonstrates the geologic significance of global continental margins for providing broadly-equitable, geographically-relevant, and high-quality CO2 storage resources. We then use principles of pore-space utilization and subsurface pressure constraints together with analogs of historic industry well deployment rates to demonstrate how the required storage capacity can be developed as a function of time and technical maturity to enable the global deployment of offshore storage for facilitating 2DS. Our analysis indicates that 10–14 thousand CO2 injection wells will be needed globally by 2050 to achieve this goal.
Hyperglycemia and Salivary Gland Dysfunction in the Non-obese Diabetic Mouse: Caveats for Preclinical Studies in Sjögren’s Syndrome
Authors: Allushi Bujana , Bagavant Harini , Papinska Joanna , Deshmukh Umesh S.
Published: November 2019

The Non-obese Diabetic (NOD) mouse model for type I diabetes also develops some features of Sjögren’s syndrome (SS). Since the source of the mice and the environment exert a strong influence on diabetes, this study investigated SS development in NOD mice obtained from two vendors. Female NOD mice from The Jackson Laboratory (JAX) and Taconic Biosciences were monitored for blood glucose and pilocarpine-induced salivation. The gut microbiome was analyzed by 16S rRNA sequencing of stool DNA. At euthanasia, serum cytokines and sialoadenitis severity were evaluated. The onset of diabetes was significantly accelerated in JAX mice compared to Taconic mice. Although the gut microbiome between the two groups was distinct, both groups developed sialoadenitis. There was no correlation between the severity of sialoadenitis and reduced saliva production. Instead, salivary gland dysfunction was associated with hyperglycemia and elevation of serum IL1β, IL16, and CXCL13. Our data suggest that inflammatory pathways linked with hyperglycemia are confounding factors for salivary gland dysfunction in female NOD mice, and might not be representative of the mechanisms operative in SS patients. Considering that NOD mice have been used to test numerous experimental therapies for SS, caution needs to be exerted before advancing these therapeutics for human trials.
Low-cost photodetector architectures fabricated at room-temperature using nano-engineered silicon wafer and sol-gel TiO2 – based heterostructures
Authors: Banerjee Debika , Asuo Ivy M. , Pignolet Alain , Cloutier Sylvain G.
Published: November 2019

In the last decades, significant research has been done on the nanocrystalline forms of titanium dioxide (TiO2). Amorphous TiO2 has not been studied intensively despite being significantly less expensive compared to crystalline TiO2. This study reveals significant improvement in UV-VIS photodetection properties from heterostructures fabricated in ambient environment using n-type silicon nanowire arrays and amorphous TiO2 sol-gel. Our ultra-low-cost UV-VIS photodetectors can cover a wide range of applications. We report fast rise/decay time constants of 0.23 ms/0.17 ms and high responsivity up-to 6.0 A/W in the UV and 25.0 A/W in the visible range under low (1 V) external bias. The large surface area due to the nanowire array architecture leads to 2 orders of magnitude enhancement in photo-response. Besides the final electrode deposition, the entire device fabrication is performed using low-cost, all solution-based methods in ambient conditions. These low-cost UV-Visible broadband photodetectors can potentially serve a wide range of applications.