bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Governance of Artificial Intelligence through Ethics Guidelines
Authors: LARSSON Stefan
Published: October 2020

This article uses a socio-legal perspective to analyze the use of ethics guidelines as a governance tool in the development and use of artificial intelligence (AI). This has become a central policy area in several large jurisdictions, including China and Japan, as well as the EU, focused on here. Particular emphasis in this article is placed on the Ethics Guidelines for Trustworthy AI published by the EU Commission’s High-Level Expert Group on Artificial Intelligence in April 2019, as well as the White Paper on AI, published by the EU Commission in February 2020. The guidelines are reflected against partially overlapping and already-existing legislation as well as the ephemeral concept construct surrounding AI as such. The article concludes by pointing to (1) the challenges of a temporal discrepancy between technological and legal change, (2) the need for moving from principle to process in the governance of AI, and (3) the multidisciplinary needs in the study of contemporary applications of data-dependent AI.
COVID-19 and Global Health Security: Overview of the Global Health Security Alliance, COVID-19 Response, African Countries’ Approaches, and Ethics
Authors: Yimer Belete , Ashebir Wassachew , Wolde Awraris , Teshome Muluken
Published: October 2020

Public health emergencies can arise from a wide range of causes, one of which includes outbreaks of contagion. The world has continued to be threatened by various infectious outbreaks of different types that have global consequences. While all pandemics are unique in their level of transmission and breadth of impact, the 2019 coronavirus disease (COVID-19) pandemic is the deepest global crisis of the 21st century, which has affected nearly every country globally. Yet, going forward, there will be a continued need for global health security resources to protect people around the world against increasing infectious disease outbreaks frequency and intensity. Pandemic response policies and processes all need to be trusted for effective and ethical pandemic response. As the world can learn during the past few years about frequent infectious disease outbreaks, (these) diseases respect no borders, and, therefore, our spirit of solidarity must respect no borders in our efforts to stop the ongoing COVID-19 pandemic and be better prepared to respond effectively to a health crisis in the future.
Salutation and Salvation in Early Modern Theology
Authors: Hillman David
Published: October 2020

At first glance, salutation and salvation could hardly be farther apart: the one ephemeral and everyday, the other eternal, of supreme importance. How should one understand the link, often insisted upon by Christian theologians, between the transience of a salutation and the transcendence of salvation? My argument in this essay is bifold: I first demonstrate that early modern writers, and especially Protestant theologians, regarded salutations as profoundly linked to salvation. I then argue that at the heart of this close association is an issue of temporality—a matter of infusing mundane, mortal time with the extra-temporal, ineffable quality of eternity.
Displacing China: The Martini-BlaeuNovus Atlas Sinensisand the Late Renaissance Shift in Representations of East Asia
Authors: Cams Mario
Published: October 2020

In the mid-seventeenth century, as the first full atlas of East Asia became available on the European book market, a dramatic shift took place in textual and visual representations of the Far East. The atlas, titled “Novus Atlas Sinensis” (1655), was the product of a cooperation between Joan Blaeu, who headed one of Europe's foremost commercial publishing houses, and Martino Martini, a prominent Jesuit missionary to China. This study shows how the Martini-Blaeu atlas thoroughly challenged the worldview of late Renaissance audiences by tracing and reconstructing a series of displacements that facilitated its production process.
LARGE VALUES OF L-FUNCTIONS ON THE 1-LINE
Authors: DIXIT ANUP B. , MAHATAB KAMALAKSHYA
Published: October 2020

We study lower bounds of a general family of L-functions on the

$1$
-line. More precisely, we show that for any

$F(s)$
in this family, there exist arbitrarily large t such that

$F(1+it)\geq e^{\gamma _F} (\log _2 t + \log _3 t)^m + O(1)$
, where m is the order of the pole of

$F(s)$
at

$s=1$
. This is a generalisation of the result of Aistleitner, Munsch and Mahatab [‘Extreme values of the Riemann zeta function on the

$1$
-line’, Int. Math. Res. Not. IMRN2019(22) (2019), 6924–6932]. As a consequence, we get lower bounds for large values of Dedekind zeta-functions and Rankin-Selberg L-functions of the type

$L(s,f\times f)$
on the

$1$
-line.
A repeated cross-sectional survey assessing university students' stress, depression, anxiety, and suicidality in the early stages of the COVID-19 pandemic in Poland
Authors: Debowska Agata , Horeczy Beata , Boduszek Daniel , Dolinski Dariusz
Published: October 2020

Background

The time of widespread outbreaks of infectious diseases can lead to elevated stress and mental health problems among all persons affected, and in particular those sub-groups of the population that are at an increased risk of mental health problems. One such vulnerable group constitutes university students. The aim of this study is to assess stress, depression, anxiety, and suicidality among different groups of university students (medical, psychology, and other).

Methods

Using a repeated cross-sectional study design, we collected survey data among a large sample of 7228 university students from Poland (mean age = 22.78, s.d. = 4.40; 81% female). Data were collected in five waves, during the first 2 months of the COVID-19 pandemic in Europe (March and April 2020).

Results

The results demonstrate a significant increase in depression levels as the pandemic was progressing. We also found that female students scored significantly higher than male students on depression, anxiety, and stress. Psychology students recorded the lowest scores on depression and anxiety. Young adult students (aged 18–24 years) had more symptoms of depression, anxiety, and suicidality than adult students (⩾25 years).

Conclusions

These results provide insights into stress and mental health among university students during the early stages of the COVID-19 pandemic. Findings can be used for a more effective identification of students who may struggle during next stages of the pandemic and future crises.
Development of an Autonomous Robotics Platform for Road Marks Painting Using Laser Simulator and Sensor Fusion Technique
Authors: Ali Mohammed A. H. , Mailah Musa , Moiduddin Khaja , Ameen Wadea , Alkhalefah Hisham
Published: October 2020

The design and experimental works of an autonomous robotic platform for road marks painting are presented in this paper as the first autonomous system of its kind. The whole system involves two main sub-systems, namely: an autonomous mobile robot navigation system which is used for recognizing the roads and estimating the position of road marks, and automatic road marks painting system that is attached to the mobile robot platform to control the spray of the paint on the road’s surface. The experimental results show the capability of the proposed system to perform the task of autonomous road marks painting with accuracy of ±10 cm.
Developing an agency's position with respect to patient involvement in health technology assessment: the importance of the organizational culture
Authors: Cleemput Irina , Dauvrin Marie , Kohn Laurence , Mistiaen Patriek , Christiaens Wendy , Léonard Christian
Published: October 2020

The Belgian Health Care Knowledge Centre (KCE) formally involves stakeholders in HTA since 2012. Patients are treated as one stakeholder amongst others, but it is recognized that patient involvement (PI) requires a different approach. The success of implementing PI depends, however, on the organizational culture toward PI.

Objectives

The objective of this study was to map the PI culture at KCE in the context of the development of organization-wide supported position statements about PI.

Methods

A nominal group technique was used to measure the PI culture at KCE. Arguments for and against PI and conditions for PI in different phases of the HTA process were collected. A literature review and interviews fed the draft position statements, for which support was assessed by means of a two-round Delphi process.

Results

Arguments in favor of PI in HTA related to the relevance of the scope, expertise with data collection, bringing in fresh ideas for study design, access to survey participants, validation of data analyses, adherence to recommendations. Disadvantages and risks included the lack of scientific knowledge of involved patients, resources requirements, conflicts of interest, and heterogeneity within patient populations. Conditions for meaningful PI referred to measures mitigating the identified disadvantages. Eighteen position statements supported by KCE could be formulated.

Conclusion

The KCE culture seems predominantly positive toward PI, although attitudes vary between HTA researchers. KCE recognizes the potential value of PI in HTA, but considers the level of involvement to be contingent on the topic and phase in the HTA process.
Reconsidering theignorabimus: du Bois-Reymond and the hard problem of consciousness
Authors: Pecere Paolo
Published: October 2020

Argument

In this paper I present an interpretation of du Bois-Reymond’s thesis on the impossibility of a scientific explanation of consciousness and of its present importance. I reconsider du Bois-Reymond’s speech “On the limits of natural science” (1872) in the context of nineteenth-century German philosophy and neurophysiology, pointing out connections and analogies with contemporary arguments on the “hard problem of consciousness.” Du Bois-Reymond’s position turns out to be grounded on an epistemological argument and characterized by a metaphysical skepticism, motivated by the unfruitful speculative tendency of contemporary German philosophy and natural science. In the final sections, I show how contemporary research can benefit from a reconsideration of this position and its context of emergence, which is a good vantage point to trace open problems in consciousness studies back to their historical development.
Return to Status Quo Ante: The Need for Robust and Reversible Pandemic Emergency Measures
Authors: RAINEY STEPHEN , GIUBILINI ALBERTO
Published: October 2020

This paper presents a normative analysis of restrictive measures in response to a pandemic emergency. It applies to the context presented by the Corona virus disease 2019 (COVID-19) global outbreak of 2019, as well as to future pandemics. First, a Millian-liberal argument justifies lockdown measures in order to protect liberty under pandemic conditions, consistent with commonly accepted principles of public health ethics. Second, a wider argument contextualizes specific issues that attend acting on the justified lockdown for western liberal democratic states, as modeled on discourse and accounted for by Jürgen Habermas. The authors argue that a range of norms are constructed in societies that, justifiably, need to be curtailed for the pandemic. The state has to take on the unusual role of sole guardian of norms under emergency pandemic conditions. Consistently with both the Millian-liberal justification and elements of Habermasian discourse ethics, they argue that that role can only be justified where it includes strategy for how to return political decisionmaking to the status quo ante. This is because emergency conditions are only justified as a means to protecting prepandemic norms. To this end, the authors propose that an emergency power committee is necessary to guarantee that state action during pandemic is aimed at re-establishing the conditions of legitimacy of government action that ecological factors (a virus) have temporarily curtailed.
Five steps towards a global reset: lessons from COVID-19
Authors: Hawkes Corinna
Published: October 2020

COVID-19 has stimulated calls for a ‘global reset’ to address major global challenges and ‘build back better’. This Intelligence Briefing makes the case that the experience of COVID-19 itself, particularly the way it reverberated across multiple systems, shines light on the vital steps needed to advance a global reset. It brings together the evidence that the causes, severity and effects of COVID-19 cut across multiple interconnected systems, notably environmental, health, political, social, economic and food systems, as did the responses to it. All of these systems affected each other: responses implemented to address problems in one system inevitably led to effects on others. This Intelligence Briefing uses this evidence to identify five practical steps needed to advance a global reset. First, train systems leaders. Second, employ a new cadre of ‘systems connectors’. Third, identify solutions across systems. Fourth, manage trade-offs for the long and short term. Fifth, kick-start system redesign for co-benefits. Implementing these steps will be extraordinarily challenging, especially given the short-term imperative to ‘bounce back’. But for any business, organization, government or United Nations agency serious about addressing long-term sustainability challenges, the opportunity is there to use these five practical actions to press the global reset button.
COVID Clears the Skies for Earth-Observing Drones in Nepal
Authors: Wight Andrew
Published: October 2020

When the pandemic hit Nepal and the country’s main airport drastically cut flights, a group of drone experts, local governments, and scientists saw a once-in-a-lifetime opportunity to gather geodata.
Fibers Pick Up Silicon Valley Traffic Changes During Quarantine
Authors: Fritts Rachel
Published: October 2020

Fiber-optic cables measured a 50% decline in Sand Hill Road traffic in March.
A Portable Magnetometer for Magnetic Measurements of Meter‐Sized Meteorites
Authors: Clavé Elise , Maurel Clara , Lima Eduardo A. , Shah Jay , Mansbach Elias N. , Uehara Minoru , Weiss Benjamin P.
Published: October 2020

Meteorites contain records of past magnetic fields in the form of natural remanent magnetization (NRM). A key property of meteorite magnetization that provides information about its origin is its dependence on spatial scale. In particular, understanding how the mean remanent magnetization varies from the scale of meteorites to the global scale of their parent bodies would aid in the interpretation of spacecraft magnetometry data. However, the vast majority of meteorite samples whose remanent magnetization have been measured have sizes <10 cm due to the limited size range accommodated by laboratory magnetometers. To address this limitation, we developed a portable magnetometer array that enables remanence measurements of meter‐size meteorites in a non‐magnetically shielded environment. The instrument measures both NRM and induced magnetization using two orthogonal square Helmholtz coil pairs that compensate the vertical and horizontal components of the background magnetic field. An array of four magnetometers mounted on a movable aluminum rail measures the magnetic field at multiple locations around the sample. The instrument is transportable and can be adapted to different sample sizes. After distinguishing the induced component from the remanent component of a sample's total field, the remanence can be estimated from a multipole field inversion combined with nonlinear least squares method. We validated the instrument and data processing on a magnet of known magnetic moment and measured the NRM of a meter‐sized iron meteorite.
Rethinking Lunar Mare Basalt Regolith Formation: New Concepts of Lava Flow Protolith and Evolution of Regolith Thickness and Internal Structure
Authors: Head James W. , Wilson Lionel
Published: October 2020

Lunar mare regolith is traditionally thought to have formed by impact bombardment of newly emplaced coherent solidified basaltic lava. We use new models for initial emplacement of basalt magma to predict and map out thicknesses, surface topographies and internal structures of the fresh lava flows, and pyroclastic deposits that form the lunar mare regolith parent rock, or protolith. The range of basaltic eruption types produce widely varying initial conditions for regolith protolith, including (1) autoregolith, a fragmental meter‐thick surface deposit that forms upon eruption and mimics impact‐generated regolith in physical properties, (2) lava flows with significant near‐surface vesicularity and macroporosity, (3) magmatic foams, and (4) dense, vesicle‐poor flows. Each protolith has important implications for the subsequent growth, maturation, and regional variability of regolith deposits, suggesting wide spatial variations in the properties and thickness of regolith of similar age. Regolith may thus provide key insights into mare basalt protolith and its mode of emplacement.
Emerged Coral Reefs Record Holocene Low‐Angle Normal Fault Earthquakes
Authors: Biemiller James , Taylor Frederick , Lavier Luc , Yu Tsai‐Luen , Wallace Laura , Shen Chuan‐Chou
Published: October 2020

Low‐angle normal faults (LANFs; dip <30°) accommodate kilometers of crustal extension, yet it remains unclear whether these faults can host large earthquakes or if they predominantly creep aseismically. Most active LANFs typically slip at rates of <3 mm/year. Here, we report U‐Th ages from a series of distinct levels of formerly shallow‐living corals killed by uplift‐induced emergence of the footwall of one of the world's fastest‐slipping LANFs, the Mai'iu fault in Papua New Guinea, which slips at rates of 8–12 mm/year. Coral ages and coastal morphology indicate punctuated episodic uplift events consistent with seismic slip on the Mai'iu fault. Maximum episodic uplift increments of 0.5–1.8 m imply earthquakes of Mw > 7. We present the first coral paleoseismological record of normal fault earthquakes, which constrain the timing and surface uplift patterns of multiple LANF seismic cycles and confirm that LANFs can slip in large (Mw > 7) earthquakes.
Automatic Auroral Boundary Determination Algorithm With Deep Feature and Dual Level Set
Authors: Tian Chen‐Jing , Du Hua‐Dong , Yang Ping‐Lv , Zhou Ze‐Ming , Zhao Xiao‐Feng , Zhou Su
Published: October 2020

The morphology of the auroral oval is an important geophysical parameter that helps to further understand the solar wind‐magnetosphere‐ionosphere coupling process. However, it is still a challenging task to automatically obtain auroral poleward and equatorward boundaries completely and accurately. In this paper, a new model based on the deep feature and dual level set method is proposed to extract the auroral oval boundaries in the images acquired by the Ultraviolet Imager (UVI) onboard the Polar spacecraft. With the deep feature extracted by the convolutional neural network (CNN), the corresponding deep feature energy functional is constructed and incorporated into the variational segmentation framework. The dual level set method is implemented to extract the accurate poleward and equatorward boundaries with the gradient descent flow. The experimental results on the test data set demonstrate that this model can extract complete auroral oval contours that are consistent well with annotations and owns higher accuracy compared with the previously proposed methods. Comparison between the extracted auroral boundaries and the precipitating boundaries determined by Defense Meteorological Satellite Program (DMSP) SSJ precipitating particle data validates that the proposed method is trustworthy to capture the global morphology of the auroral ovals.
Magnetic Energy Conversion and Transport in the Terrestrial Magnetotail Due to Dipolarization Fronts
Authors: Wang Lei , Huang Can , Cao Xin , Du Aimin , Ge Yasong S.
Published: October 2020

Dipolarization front (DF) is an important region involved with energy conversion and flux transport in the planet's magnetotail. Using observation data from the recent Magnetospheric Multiscale (MMS) mission, we have identified and analyzed 215 DF events. Significant magnetic energy conversion and transport are observed at the DFs, which show strong dawn‐dusk asymmetry. We find that the transport process dominates the change of local magnetic energy. Nearly 70% of the events show net Poynting flux flowing into the DF region. Such effect is more significant than local magnetic energy dissipation, averagely. When DF approaches the near‐Earth region, the net flow‐in Poynting flux decreases and magnetic energy dissipation increases. Our results suggest that the downstream magnetic energies of transient magnetic reconnections in the midtail may be transported to the near‐Earth region by one DF event after another. These intensive strikes to the magnetosphere in the near‐planet region may drive stronger storms, compared with the previous knowledge about DF.
Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases
Authors: Jang Sang-Min , Redon Christophe E. , Thakur Bhushan L. , Bahta Meriam K. , Aladjem Mirit I.
Published: October 2020

The last decade has revealed new roles for Cullin-RING ubiquitin ligases (CRLs) in a myriad of cellular processes, including cell cycle progression. In addition to CRL1, also named SCF (SKP1-Cullin 1-F box protein), which has been known for decades as an important factor in the regulation of the cell cycle, it is now evident that all eight CRL family members are involved in the intricate cellular pathways driving cell cycle progression. In this review, we summarize the structure of CRLs and their functions in driving the cell cycle. We focus on how CRLs target key proteins for degradation or otherwise alter their functions to control the progression over the various cell cycle phases leading to cell division. We also summarize how CRLs and the anaphase-promoting complex/cyclosome (APC/C) ligase complex closely cooperate to govern efficient cell cycle progression.
Acute effects of whey protein on energy intake, appetite and gastric emptying in younger and older, obese men
Authors: Oberoi Avneet , Giezenaar Caroline , Jensen Caroline , Lange Kylie , Hausken Trygve , Jones Karen L. , Horowitz Michael , Chapman Ian , Soenen Stijn
Published: October 2020

Background

Obesity is becoming more prevalent in older people. A management strategy in obese, young adults is to increase dietary protein relative to other macronutrients. It is not clear if this is effective in obese, older individuals. Obesity may be associated with diminished sensitivity to nutrients. We have reported that a 30-g whey protein drink slows gastric emptying more, and suppresses energy intake less, in older, than younger, non-obese men. The aim of this study was to determine the effect of a 30 g whey protein drink on energy intake, GE and glycaemia in obese, older and younger men.

Methods

In randomized, double-blind order, 10 younger (age: 27 ± 2 years; BMI: 36 ± 2 kg/m²), and 10 older (72 ± 1 years; 33 ± 1 kg/m²), obese men were studied twice. After an overnight fast, subjects ingested a test drink containing 30 g whey protein (120 kcal) or control (2 kcal). Postprandial gastric emptying (antral area, 2D Ultrasound) and blood glucose concentrations were measured for 180 min. Att = 180 min subjects were given a buffet meal andad libitumenergy intake was assessed.

Results

Older subjects ate non-significantly less (~20%) that the younger subjects (effect of age,P = 0.16). Whey protein had no effect on subsequent energy intake (kcal) compared to control in either the younger (decrease 3 ± 8%) or older (decrease 2 ± 8%) obese men (age effectP > 0.05, protein effectP = 0.46, age × protein interaction effectP = 0.84). Whey protein slowed gastric emptying, to a similar degree in both age groups (50% emptying time: control vs. protein young men: 255 ± 5 min vs. 40 ± 7 min; older men: 16 ± 5 min vs. 50 ± 8 min; protein effectP = 0.001, age effectP = 0.93, age × protein interaction effectP = 0.13).

Conclusions

Our data suggest that obesity may blunt/abolish the age-related effect of whey protein on suppression of energy intake.
Shaping the role of germanium vacancies in germanium telluride: metastable cubic structure stabilization, band structure modification, and stable N-type conduction
Authors: Liu Zihang , Sato Naoki , Guo Quansheng , Gao Weihong , Mori Takao
Published: October 2020

Understanding and controlling point defects in semiconductors are essential for developing advanced electronic and optoelectronic devices. Germanium telluride (GeTe), a semiconductor with a rhombohedral-to-cubic structural phase transition and a high concentration of intrinsic vacancies on the Ge sublattice, has recently attracted much interest for thermoelectric applications. However, the role of Ge vacancies in structural change and performance optimization remains obscure. Herein, we first unraveled the importance of Ge vacancies by combining first-principles calculations and Boltzmann transport theory. It is revealed that (1) Ge vacancies are more likely to spontaneously form in cubic GeTe, addressing its defective character; (2) Ge vacancies play a vital role in stabilizing cubic GeTe; and (3) Ge vacancies produce unfavorable band structure modification, leading to a reduced power factor. The following experiment found that AgInTe2 alloying promotes a symmetry change from rhombohedral to cubic and deteriorates the thermoelectric performance, in good agreement with the abovementioned conclusions. More importantly, a single-phase cubic GeTe-based material with stable n-type conduction was first discovered based on the defect chemistry approach. Our findings shed new light on the critical role of Ge vacancies in the structure-property relationship and stimulate the strategy of point defect engineering for future thermoelectric applications.
GABA uptake transporters support dopamine release in dorsal striatum with maladaptive downregulation in a parkinsonism model
Authors: Roberts Bradley M. , Doig Natalie M. , Brimblecombe Katherine R. , Lopes Emanuel F. , Siddorn Ruth E. , Threlfell Sarah , Connor-Robson Natalie , Bengoa-Vergniory Nora , Pasternack Nicholas , Wade-Martins Richard , Magill Peter J. , Cragg Stephanie J.
Published: October 2020

Striatal dopamine (DA) is critical for action and learning. Recent data show that DA release is under tonic inhibition by striatal GABA. Ambient striatal GABA tone on striatal projection neurons can be determined by plasma membrane GABA uptake transporters (GATs) located on astrocytes and neurons. However, whether striatal GATs and astrocytes determine DA output are unknown. We reveal that DA release in mouse dorsolateral striatum, but not nucleus accumbens core, is governed by GAT-1 and GAT-3. These GATs are partly localized to astrocytes, and are enriched in dorsolateral striatum compared to accumbens core. In a mouse model of early parkinsonism, GATs are downregulated, tonic GABAergic inhibition of DA release augmented, and nigrostriatal GABA co-release attenuated. These data define previously unappreciated and important roles for GATs and astrocytes in supporting DA release in striatum, and reveal a maladaptive plasticity in early parkinsonism that impairs DA output in vulnerable striatal regions.
Inhibition of oxygen dimerization by local symmetry tuning in Li-rich layered oxides for improved stability
Authors: Ning Fanghua , Li Biao , Song Jin , Zuo Yuxuan , Shang Huaifang , Zhao Zimeng , Yu Zhen , Chu Wangsheng , Zhang Kun , Feng Guang , Wang Xiayan , Xia Dingguo
Published: October 2020

Li-rich layered oxide cathode materials show high capacities in lithium-ion batteries owing to the contribution of the oxygen redox reaction. However, structural accommodation of this reaction usually results in O–O dimerization, leading to oxygen release and poor electrochemical performance. In this study, we propose a new structural response mechanism inhibiting O–O dimerization for the oxygen redox reaction by tuning the local symmetry around the oxygen ions. Compared with regular Li2RuO3, the structural response of the as-prepared local-symmetry-tuned Li2RuO3 to the oxygen redox reaction involves the telescopic O–Ru–O configuration rather than O–O dimerization, which inhibits oxygen release, enabling significantly enhanced cycling stability and negligible voltage decay. This discovery of the new structural response mechanism for the oxygen redox reaction will provide a new scope for the strategy of enhancing the anionic redox stability, paving unexplored pathways toward further development of high capacity Li-rich layered oxides.
Format chain exchange (FORCE) for high-throughput generation of bispecific antibodies in combinatorial binder-format matrices
Authors: Dengl Stefan , Mayer Klaus , Bormann Felix , Duerr Harald , Hoffmann Eike , Nussbaum Bianca , Tischler Michael , Wagner Martina , Kuglstatter Andreas , Leibrock Lea , Buldun Can , Georges Guy , Brinkmann Ulrich
Published: October 2020

Generation of bispecific antibodies (bsAbs) requires a combination of compatible binders in formats that support desired functionalities. Here, we report that bsAb-matrices can be generated by Format Chain Exchange (FORCE), enabling screening of combinatorial binder/format spaces. Input molecules for generation of bi/multi-valent bsAbs are monospecific entities similar to knob-into-hole half-antibodies, yet with complementary CH3-interface-modulated and affinity-tagged dummy-chains. These contain mutations that lead to limited interface repulsions without compromising expression or biophysical properties of educts. Mild reduction of combinations of educts triggers spontaneous chain-exchange reactions driven by partially flawed CH3-educt interfaces resolving to perfect complementarity. This generates large bsAb matrices harboring different binders in multiple formats. Benign biophysical properties and good expression yields of educts, combined with simplicity of purification enables process automation. Examples that demonstrate the relevance of screening binder/format combinations are provided as a matrix of bsAbs that simultaneously bind Her1/Her2 and DR5 without encountering binder or format-inflicted interferences.
Observation of two-dimensional Anderson localisation of ultracold atoms
Authors: White Donald H. , Haase Thomas A. , Brown Dylan J. , Hoogerland Maarten D. , Najafabadi Mojdeh S. , Helm John L. , Gies Christopher , Schumayer Daniel , Hutchinson David A. W.
Published: October 2020

Anderson localisation —the inhibition of wave propagation in disordered media— is a surprising interference phenomenon which is particularly intriguing in two-dimensional (2D) systems. While an ideal, non-interacting 2D system of infinite size is always localised, the localisation length-scale may be too large to be unambiguously observed in an experiment. In this sense, 2D is a marginal dimension between one-dimension, where all states are strongly localised, and three-dimensions, where a well-defined phase transition between localisation and delocalisation exists as the energy is increased. Here, we report the results of an experiment measuring the 2D transport of ultracold atoms between two reservoirs, which are connected by a channel containing pointlike disorder. The design overcomes many of the technical challenges that have hampered observation of localisation in previous works. We experimentally observe exponential localisation in a 2D ultracold atom system.
Disease trajectory browser for exploring temporal, population-wide disease progression patterns in 7.2 million Danish patients
Authors: Siggaard Troels , Reguant Roc , Jørgensen Isabella F. , Haue Amalie D. , Lademann Mette , Aguayo-Orozco Alejandro , Hjaltelin Jessica X. , Jensen Anders Boeck , Banasik Karina , Brunak Søren
Published: October 2020

We present the Danish Disease Trajectory Browser (DTB), a tool for exploring almost 25 years of data from the Danish National Patient Register. In the dataset comprising 7.2 million patients and 122 million admissions, users can identify diagnosis pairs with statistically significant directionality and combine them to linear disease trajectories. Users can search for one or more disease codes (ICD-10 classification) and explore disease progression patterns via an array of functionalities. For example, a set of linear trajectories can be merged into a disease trajectory network displaying the entire multimorbidity spectrum of a disease in a single connected graph. Using data from the Danish Register for Causes of Death mortality is also included. The tool is disease-agnostic across both rare and common diseases and is showcased by exploring multimorbidity in Down syndrome (ICD-10 code Q90) and hypertension (ICD-10 code I10). Finally, we show how search results can be customized and exported from the browser in a format of choice (i.e. JSON, PNG, JPEG and CSV).
Discovery of beneficial haplotypes for complex traits in maize landraces
Authors: Mayer Manfred , Hölker Armin C. , González-Segovia Eric , Bauer Eva , Presterl Thomas , Ouzunova Milena , Melchinger Albrecht E. , Schön Chris-Carolin
Published: October 2020

Genetic variation is of crucial importance for crop improvement. Landraces are valuable sources of diversity, but for quantitative traits efficient strategies for their targeted utilization are lacking. Here, we map haplotype-trait associations at high resolution in ~1000 doubled-haploid lines derived from three maize landraces to make their native diversity for early development traits accessible for elite germplasm improvement. A comparative genomic analysis of the discovered haplotypes in the landrace-derived lines and a panel of 65 breeding lines, both genotyped with 600k SNPs, points to untapped beneficial variation for target traits in the landraces. The superior phenotypic performance of lines carrying favorable landrace haplotypes as compared to breeding lines with alternative haplotypes confirms these findings. Stability of haplotype effects across populations and environments as well as their limited effects on undesired traits indicate that our strategy has high potential for harnessing beneficial haplotype variation for quantitative traits from genetic resources.
Multi-omics prediction of immune-related adverse events during checkpoint immunotherapy
Authors: Jing Ying , Liu Jin , Ye Youqiong , Pan Lei , Deng Hui , Wang Yushu , Yang Yang , Diao Lixia , Lin Steven H. , Mills Gordon B. , Zhuang Guanglei , Xue Xinying , Han Leng
Published: October 2020

Immune-related adverse events (irAEs), caused by anti-PD-1/PD-L1 antibodies, can lead to fulminant and even fatal consequences and thus require early detection and aggressive management. However, a comprehensive approach to identify biomarkers of irAE is lacking. Here, we utilize a strategy that combines pharmacovigilance data and omics data, and evaluate associations between multi-omics factors and irAE reporting odds ratio across different cancer types. We identify a bivariate regression model of LCP1 and ADPGK that can accurately predict irAE. We further validate LCP1 and ADPGK as biomarkers in an independent patient-level cohort. Our approach provides a method for identifying potential biomarkers of irAE in cancer immunotherapy using both pharmacovigilance data and multi-omics data.
Overestimation of the effect of climatic warming on spring phenology due to misrepresentation of chilling
Authors: Wang Huanjiong , Wu Chaoyang , Ciais Philippe , Peñuelas Josep , Dai Junhu , Fu Yongshuo , Ge Quansheng
Published: October 2020

Spring warming substantially advances leaf unfolding and flowering time for perennials. Winter warming, however, decreases chilling accumulation (CA), which increases the heat requirement (HR) and acts to delay spring phenology. Whether or not this negative CA-HR relationship is correctly interpreted in ecosystem models remains unknown. Using leaf unfolding and flowering data for 30 perennials in Europe, here we show that more than half (7 of 12) of current chilling models are invalid since they show a positive CA-HR relationship. The possible reason is that they overlook the effect of freezing temperature on dormancy release. Overestimation of the advance in spring phenology by the end of this century by these invalid chilling models could be as large as 7.6 and 20.0 days under RCPs 4.5 and 8.5, respectively. Our results highlight the need for a better representation of chilling for the correct understanding of spring phenological responses to future climate change.
Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death
Authors: Deng Hongzhang , Yang Weijing , Zhou Zijian , Tian Rui , Lin Lisen , Ma Ying , Song Jibin , Chen Xiaoyuan
Published: October 2020

Immunogenic cell death (ICD) and tumour-infiltrating T lymphocytes are severely weakened by elevated reactive oxygen species (ROS) in the tumour microenvironment. It is therefore of critical importance to modulate the level of extracellular ROS for the reversal of immunosuppressive environment. Here, we present a tumour extracellular matrix (ECM) targeting ROS nanoscavenger masked by pH sensitive covalently crosslinked polyethylene glycol. The nanoscavenger anchors on the ECM to sweep away the ROS from tumour microenvironment to relieve the immunosuppressive ICD elicited by specific chemotherapy and prolong the survival of T cells for personalized cancer immunotherapy. In a breast cancer model, elimination of the ROS in tumour microenvironment elicited antitumour immunity and increased infiltration of T lymphocytes, resulting in highly potent antitumour effect. The study highlights a strategy to enhance the efficacy of cancer immunotherapy by scavenging extracellular ROS using advanced nanomaterials.
TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control
Authors: Douse Christopher H. , Tchasovnikarova Iva A. , Timms Richard T. , Protasio Anna V. , Seczynska Marta , Prigozhin Daniil M. , Albecka Anna , Wagstaff Jane , Williamson James C. , Freund Stefan M. V. , Lehner Paul J. , Modis Yorgo
Published: October 2020

The HUSH complex represses retroviruses, transposons and genes to maintain the integrity of vertebrate genomes. HUSH regulates deposition of the epigenetic mark H3K9me3, but how its three core subunits — TASOR, MPP8 and Periphilin — contribute to assembly and targeting of the complex remains unknown. Here, we define the biochemical basis of HUSH assembly and find that its modular architecture resembles the yeast RNA-induced transcriptional silencing complex. TASOR, the central HUSH subunit, associates with RNA processing components. TASOR is required for H3K9me3 deposition over LINE-1 repeats and repetitive exons in transcribed genes. In the context of previous studies, this suggests that an RNA intermediate is important for HUSH activity. We dissect the TASOR and MPP8 domains necessary for transgene repression. Structure-function analyses reveal TASOR bears a catalytically-inactive PARP domain necessary for targeted H3K9me3 deposition. We conclude that TASOR is a multifunctional pseudo-PARP that directs HUSH assembly and epigenetic regulation of repetitive genomic targets.
SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate
Authors: Olagnier David , Farahani Ensieh , Thyrsted Jacob , Blay-Cadanet Julia , Herengt Angela , Idorn Manja , Hait Alon , Hernaez Bruno , Knudsen Alice , Iversen Marie Beck , Schilling Mirjam , Jørgensen Sofie E. , Thomsen Michelle , Reinert Line S. , Lappe Michael , Hoang Huy-Dung , Gilchrist Victoria H. , Hansen Anne Louise , Ottosen Rasmus , Nielsen Camilla G. , Møller Charlotte , van der Horst Demi , Peri Suraj , Balachandran Siddharth , Huang Jinrong , Jakobsen Martin , Svenningsen Esben B. , Poulsen Thomas B. , Bartsch Lydia , Thielke Anne L. , Luo Yonglun , Alain Tommy , Rehwinkel Jan , Alcamí Antonio , Hiscott John , Mogensen Trine H. , Paludan Søren R. , Holm Christian K.
Published: October 2020

Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here, we demonstrate that the NRF2 antioxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular antiviral program that potently inhibits replication of SARS-CoV2 across cell lines. The inhibitory effect of 4-OI and DMF extends to the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, 4-OI and DMF limit host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and in suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2.
Evolution of communication signals and information during species radiation
Authors: Garcia Maxime , Theunissen Frédéric , Sèbe Frédéric , Clavel Julien , Ravignani Andrea , Marin-Cudraz Thibaut , Fuchs Jérôme , Mathevon Nicolas
Published: October 2020

Communicating species identity is a key component of many animal signals. However, whether selection for species recognition systematically increases signal diversity during clade radiation remains debated. Here we show that in woodpecker drumming, a rhythmic signal used during mating and territorial defense, the amount of species identity information encoded remained stable during woodpeckers’ radiation. Acoustic analyses and evolutionary reconstructions show interchange among six main drumming types despite strong phylogenetic contingencies, suggesting evolutionary tinkering of drumming structure within a constrained acoustic space. Playback experiments and quantification of species discriminability demonstrate sufficient signal differentiation to support species recognition in local communities. Finally, we only find character displacement in the rare cases where sympatric species are also closely related. Overall, our results illustrate how historical contingencies and ecological interactions can promote conservatism in signals during a clade radiation without impairing the effectiveness of information transfer relevant to inter-specific discrimination.
Ternary MOF-on-MOF heterostructures with controllable architectural and compositional complexity via multiple selective assembly
Authors: Liu Chao , Sun Qiang , Lin Lina , Wang Jing , Zhang Chaoqi , Xia Chunhong , Bao Tong , Wan Jingjing , Huang Rong , Zou Jin , Yu Chengzhong
Published: October 2020

Assembly of different metal-organic framework (MOF) building blocks into hybrid MOF-on-MOF heterostructures is promising in chemistry and materials science, however the development of ternary MOF-on-MOF heterostructures with controllable architectural and compositional complexity is challenging. Here we report the synthesis of three types of ternary MOF-on-MOF heterostructures via a multiple selective assembly strategy. This strategy relies on the choice of one host MOF with more than one facet that can arrange the growth of a guest MOF, where the arrangement is site-selective without homogenous growth of guest MOF or homogenous coating of guest on host MOF. The growth of guest MOF on a selected site of host MOF in each step provides the opportunity to further vary the combinations of arrangements in multiple steps, leading to ternary MOF-on-MOF heterostructures with tunable complexity. The developed strategy paves the way towards the rational design of intricate and unprecedented MOF-based superstructures for various applications.
Author Correction: High-temperature-resistant silicon-polymer hybrid modulator operating at up to 200 Gbit s−1 for energy-efficient datacentres and harsh-environment applications
Authors: Lu Guo-Wei , Hong Jianxun , Qiu Feng , Spring Andrew M. , Kashino Tsubasa , Oshima Juro , Ozawa Masa-aki , Nawata Hideyuki , Yokoyama Shiyoshi
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A global database of plant production and carbon exchange from global change manipulative experiments
Authors: Song Jian , Ru Jingyi , Zheng Mengmei , Wang Haidao , Fan Yongge , Yue Xiaojing , Yu Kejia , Zhou Zhenxing , Shao Pengshuai , Han Hongyan , Lei Lingjie , Zhang Qian , Li Xiaoming , Su Fanglong , Zhang Kesheng , Wan Shiqiang
Published: October 2020

Numerous ecosystem manipulative experiments have been conducted since 1970/80 s to elucidate responses of terrestrial carbon cycling to the changing atmospheric composition (CO2 enrichment and nitrogen deposition) and climate (warming and changing precipitation regimes), which is crucial for model projection and mitigation of future global change effects. Here, we extract data from 2,242 publications that report global change manipulative experiments and build a comprehensive global database with 5,213 pairs of samples for plant production (productivity, biomass, and litter mass) and ecosystem carbon exchange (gross and net ecosystem productivity as well as ecosystem and soil respiration). Information on climate characteristics and vegetation types of experimental sites as well as experimental facilities and manipulation magnitudes subjected to manipulative experiments are also included in this database. This global database can facilitate the estimation of response and sensitivity of key terrestrial carbon-cycling variables under future global change scenarios, and improve the robust projection of global change‒terrestrial carbon feedbacks imposed by Earth System Models.
Question-driven summarization of answers to consumer health questions
Authors: Savery Max , Abacha Asma Ben , Gayen Soumya , Demner-Fushman Dina
Published: October 2020

Automatic summarization of natural language is a widely studied area in computer science, one that is broadly applicable to anyone who needs to understand large quantities of information. In the medical domain, automatic summarization has the potential to make health information more accessible to people without medical expertise. However, to evaluate the quality of summaries generated by summarization algorithms, researchers first require gold standard, human generated summaries. Unfortunately there is no available data for the purpose of assessing summaries that help consumers of health information answer their questions. To address this issue, we present the MEDIQA-Answer Summarization dataset, the first dataset designed for question-driven, consumer-focused summarization. It contains 156 health questions asked by consumers, answers to these questions, and manually generated summaries of these answers. The dataset’s unique structure allows it to be used for at least eight different types of summarization evaluations. We also benchmark the performance of baseline and state-of-the-art deep learning approaches on the dataset, demonstrating how it can be used to evaluate automatically generated summaries.