bluuebunny/crossref_metadata_2025 huggingface dataset:
Choice Architecture for Nudges to Support Constructive Learning in Active Video Watching
Authors: Dimitrova Vania , Mitrovic Antonija
Published: August 2021

Video-based learning is widely used today in both formal education and informal learning in a variety of contexts. Videos are especially powerful for transferable skills learning (e.g. communicating, negotiating, collaborating), where contextualization in personal experience and ability to see different perspectives are crucial. With the ubiquity of widely available video content, video-based learning is seen as one of the main strategies to provide engaging learning environments. However, numerous studies show that to learn effectively while watching videos, students need to engage actively with video content. We have developed an active video watching platform (AVW-Space) to facilitate engagement with video content by providing means for constructive learning. The initial studies with AVW-Space on presentation skills show that only students who commented on videos and who rated comments written by their peers have improved their understanding of the target transferable skill. In order to foster deeper engagement, we designed a choice architecture and a set of nudges to encourage students to engage deeper. We conducted two studies investigating the effect of nudges. The results provide evidence that the initial set of implemented nudges is effective: the students who received nudges wrote more comments, used different aspects, and there were more students who wrote comments. The nudges were particularly helpful for undergraduate students who were less experienced in self-regulated learning. Future work includes designing additional nudges to enhance student engagement by improving the quality of comments and by encouraging participation in collaborative activities.
The impacts of artificial intelligence techniques in augmentation of cybersecurity: a comprehensive review
Authors: Naik Binny , Mehta Ashir , Yagnik Hiteshri , Shah Manan
Published: August 2021

Given the prevailing state of cybersecurity, it is reasonable to understand why cybersecurity experts are seriously considering artificial intelligence as a potential field that can aid improvements in conventional cybersecurity techniques. Various progressions in the field of technology have helped to mitigate some of the issues relating to cybersecurity. These advancements can be manifested by Big Data, Blockchain technology, Behavioral Analytics, to name but a few. The paper overviews the effects of applications of these technologies in cybersecurity. The central purpose of the paper is to review the application of AI techniques in analyzing, detecting, and fighting various cyberattacks. The effects of the implementation of conditionally classified “distributed” AI methods and conveniently classified “compact” AI methods on different cyber threats have been reviewed. Furthermore, the future scope and challenges of using such techniques in cybersecurity, are discussed. Finally, conclusions have been drawn in terms of evaluating the employment of different AI advancements in improving cybersecurity.
A microfluidic approach to studying the injection flow of concentrated albumin solutions
Authors: Lanzaro Alfredo
Published: August 2021

Subcutaneous injection by means of prefilled syringes allows patients to self-administrate high-concentration (100 g/L or more) protein-based drugs. Although the shear flow of concentrated globulins or monoclonal antibodies has been intensively studied and related to the injection force proper of SC processes, very small attention has been paid to the extensional behavior of this category of complex fluids. This work focuses on the flow of concentrated bovine serum albumin (BSA) solutions through a microfluidic “syringe-on-chip” contraction device which shares some similarities with the geometry of syringes used in SC self-injection. By comparing the velocity and pressure measurements in complex flow with rheometric shear measurements obtained by means of the “Rheo-chip” device, it is shown that the extensional viscosity plays an important role in the injection process of protinaceous drugs.

Article Highlights

A microfluidic “syringe on chip” device mimicking the injection flow of protinaceous drugs has been developed.

The velocity field of concentrated BSA solutions through the “syringe on chip” is Newtonian-like.

The extensional viscosity of concentrated protein solutions should also be considered when computing injection forces through needles.
A Computational Tool for the Design of Hybrid Rockets
Authors: Zolla Paolo Maria , Migliorino Mario Tindaro , Bianchi Daniele , Nasuti Francesco , Pellegrini Rocco Carmine , Cavallini Enrico
Published: August 2021

A computational tool able to perform a fast analysis of hybrid rocket engines is presented, describing briefly the mathematical and physical models used. Validation of the code is also shown: 16 different static firing tests available in the open literature are used to compare measured operational parameters such as chamber pressure, thrust, and specific impulse with the code’s output. The purpose of the program is to perform rapid evaluation and assessment on a possible first design of hybrid rockets, without relying on computationally expensive simulations or onerous experimental tests. The validated program considers as benchmark and study case the design of a liquid-oxygen/paraffin hybrid rocket engine to be used as the upper stage of a small launcher derived from VEGA building blocks. A full-factorial parametric analysis is performed for both pressure-fed and pump-fed systems to find a configuration that delivers the equivalent total impulse of a VEGA-like launcher third and fourth stage as a first evaluation. This parametric analysis is also useful to highlight how the oxidizer injection system, the fuel grain design, and the nozzle features affect the performance of the rocket.
The coming together of allosteric and phosphorylation mechanisms in the molecular integration of A2A heteroreceptor complexes in the dorsal and ventral striatal-pallidal GABA neurons
Authors: Borroto-Escuela Dasiel O. , Ferraro Luca , Beggiato Sarah , Narváez Manuel , Fores-Pons Ramon , Alvarez-Contino Jose E. , Wydra Karolina , Frankowska Małgorzata , Bader Michael , Filip Małgorzata , Fuxe Kjell
Published: August 2021

The role of adenosine A2A receptor (A2AR) and striatal-enriched protein tyrosine phosphatase (STEP) interactions in the striatal-pallidal GABA neurons was recently discussed in relation to A2AR overexpression and cocaine-induced increases of brain adenosine levels. As to phosphorylation, combined activation of A2AR and metabotropic glutamate receptor 5 (mGluR5) in the striatal-pallidal GABA neurons appears necessary for phosphorylation of the GluA1 unit of the AMPA receptor to take place. Robert Yasuda (J Neurochem 152: 270–272, 2020) focused on finding a general mechanism by which STEP activation is enhanced by increased A2AR transmission in striatal-pallidal GABA neurons expressing A2AR and dopamine D2 receptor. In his Editorial, he summarized in a clear way the significant effects of A2AR activation on STEP in the dorsal striatal-pallidal GABA neurons which involves a rise of intracellular levels of calcium causing STEP activation through its dephosphorylation. However, the presence of the A2AR in an A2AR-fibroblast growth factor receptor 1 (FGFR1) heteroreceptor complex can be required in the dorsal striatal-pallidal GABA neurons for the STEP activation. Furthermore, Won et al. (Proc Natl Acad Sci USA 116: 8028–8037, 2019) found in mass spectrometry experiments that the STEP splice variant STEP61 can bind to mGluR5 and inactivate it. In addition, A2AR overexpression can lead to increased formation of A2AR-mGluR5 heterocomplexes in ventral striatal-pallidal GABA neurons. It involves enhanced facilitatory allosteric interactions leading to increased Gq-mediated mGluR5 signaling activating STEP. The involvement of both A2AR and STEP in the actions of cocaine on synaptic downregulation was also demonstrated. The enhancement of mGluR5 protomer activity by the A2AR protomer in A2AR-mGluR5 heterocomplexes in the nucleus accumbens shell appears to have a novel significant role in STEP mechanisms by both enhancing the activation of STEP and being a target for STEP61.
Factors affecting 30-day postoperative complications after emergency surgery during the COVID-19 outbreak: A multicentre cohort study
Authors: de Bock Ellen , Filipe Mando D. , Pronk Apollo , Boerma Djamila , Heikens Joost T. , Verheijen Paul M. , Vriens Menno R. , Richir Milan C.
Published: August 2021

ABSTRACT

Introduction:

Coronavirus disease 2019 (COVID-19) has influenced (surgical) care worldwide. Measures were taken to prioritize surgical care in order to maintain capacity for COVID-19 healthcare. However, the influence of these measures on emergency surgery is limited. Therefore, the aim of this study is to describe the trends in emergency surgery and determine the factors influencing the risk of postoperative complications during the first wave of the COVID-19 pandemic.

Methods:

This multicentre retrospective cohort study investigated all emergency patients operated on from March 9th to June 30th, 2020. The primary endpoint was identifying the number of emergency surgical procedures performed. Secondary endpoints were determining the number of postoperative complications and factors determining the risk of postoperative complications, which were calculated by multivariate analysis with odds ratio (OR) and 95% confidence (CI) intervals.

Results:

In total, 1399 patients who underwent an emergency surgical procedure were included. An increase in the number of emergency vascular and trauma surgical procedures occurred during the study period. In contrast, the number of emergency general and oncological surgical procedures performed remained stable. An increased age (OR 1.01, 95% CI 1.00–1.02; p = 0.024), American Society of Anaesthesiologists (ASA) (OR 1.34, 95% CI 1.09–1.64; p = 0.005), and surgical discipline were independent predictors for an increased risk of postoperative complications.

Conclusion:

The performance of emergency vascular and trauma surgical procedures increased. The performance of emergency general and oncological surgical procedures remained stable. In addition, increased age, ASA, and surgical discipline were independent predictors for an increased risk of postoperative complications.

Highlights
Uncertainty in cyber de-responsibilisation
Authors: Renaud Karen , Flowerday Stephen , van der Schyff Karl
Published: August 2021

The sociologist Norbert Elias argued that the ability to take responsibility is part of a ‘civilizing process’. 1 Neoliberal governments appear to agree with this, because they have ‘responsibilised’ their citizens in many domains. 2 Pellandini-Simányi and Conte explain that the concept of responsibilisation refers to the assigning of responsibility to citizens and the social-cultural factors that persuade citizens to embrace those responsibilities. 3
Effect of starvation on the cold tolerance of adultDrosophila suzukii(Diptera: Drosophilidae)
Authors: De Ro Madelena , Enriquez Thomas , Bonte Jochem , Ebrahimi Negin , Casteels Hans , De Clercq Patrick , Colinet Hervé
Published: August 2021

The spotted wing drosophila,Drosophila suzukii, is an invasive pest in Europe and North America. Access to resources may be challenging in late fall, winter and early spring and flies may suffer from food deprivation along with cold stress in these periods. Whereas a plethora of studies have been performed on the overwintering capacity ofD. suzukii, the effects of starvation on the fly's cold tolerance have not been addressed. In the present study, youngD. suzukiiadults (reared at 25°C, LD 12:12 h) were deprived of food for various periods (0, 12, 24 and 36 h), after which chill coma recovery time, critical thermal minimum, as well as acute and chronic cold tolerance were assessed. Additionally, the body composition of adults (body mass, water content, total lipid, glycerol, triglycerides, glucose and proteins) before and after starvation periods was analysed to confirm that starvation had detectable effects. Starved adults had a lower body mass, and both lipid and carbohydrate levels decreased with starvation time. Starvation slightly increased critical thermal minimum and affected chill coma recovery time; however, these changes were not gradual with starvation duration. Starvation promoted acute cold tolerance in both sexes. This effect appeared faster in males than in females. Food deprivation also led to enhanced survival to chronic cold stress. Short-term starvation was thus associated with significant changes in body composition inD. suzukii, and these alterations could alter some ecologically relevant traits related to cold tolerance, particularly in females. Our results suggest that food deprivation during short time (<36 h) can promote cold tolerance (especially survival after a cold stress) ofD. suzukiiflies. Future studies should address the ecological significance of these findings as short food deprivation may occur in the fields on many occasions and seasons.
Aristocratic Insolenzia and the Role of Senates in Machiavelli's Mixed Republic
Authors: McCormick John P.
Published: August 2021

This essay offers an alternative to influential interpretations of elites, peoples, and senates in Niccolò Machiavelli's theory of mixed republics. It analyzes in greater depth both Machiavelli's ascription of the morally objectionable and politically dangerous trait of insolenzia to the nobles as a social class; and his justifications for the establishment of senates as institutions that partially remedy the problem of aristocratic insolence—justifications that depart from traditional Ciceronian and Polybian standards. Machiavelli demonstrates in The Prince, the Discourses, and the Florentine Histories that republics with senates, such as ancient Rome, manage to mollify aristocratic insolence, while those lacking them, like modern Florence, permit such insolence to proliferate unchecked. Moreover, Machiavelli intimates, republics that collectively gather nobles within senate chambers are afforded the opportunity to entirely eliminate aristocratic insolence. The essay concludes with an analysis of senatorial institutions in Machiavelli's “Discursus on Florentine Matters.”
On the Magnitude of the Gods in Materialist Theology and Greek Art
Authors: Hedreen Guy
Published: August 2021

In this paper, I address one characteristic of Classical Greek votive reliefs that has troubled scholars: the size of the gods. The reliefs depict mortal worshippers approaching gods and goddesses who are, almost invariably, larger in stature than the mortals. Scholars have generally explained the difference in scale to be art historical, rather than theological, in significance. Either the larger scale is a visual expression of the hierarchical superiority of the gods or the images of the gods represent over-life-size statues. In addition, it is widely accepted that votive reliefs are products of unsophisticated religious belief, ignorant of the conceptualization of an imperceptible, non-corporeal deity in Classical philosophy. In this paper, I accept the artistic proposition of votive reliefs at face value: in this genre, the gods are living, visible, material bodies, most often anthropomorphic in form and always larger in magnitude than mortals. I identify one significant parallel for this interpretation within Greek and Roman thought, namely, the conception of gods within the materialist theology developed by the late Classical writer Epicurus and, in part at least, by the fifth-century BC writer Demokritos. In the writings of the Epicureans and, it appears, the atomists, as in the votive reliefs, gods are human in form, very beautiful, self-sufficient, larger than humans in size and known by mortals through visual perception.
The Shang-Yin Dynasty and the An-yang Finds
Authors: Yetts W. Perceval
Published: August 2021

The fact seems strange that thirty years elapsed between the known discovery of inscribed bones and tortoise shells near An-yang and the first systematic exploration of the site. Towards the end of 1928 digging was begun by an expedition sent by the National Research Institute of History and Philology, and partly financed by the Freer Gallery of Art, Smithsonian Institution. The work suffered from obstruction owing to the prevailing unrest; but several times it has been resumed, and three volumes have appeared under the title Preliminary Reports of Excavations at Anyang. These give interim accounts of the varied results which provide important contributions to history and archaeology.
Co-integration with score-driven models: an application to US real GDP growth, US inflation rate, and effective federal funds rate
Authors: Blazsek Szabolcs , Escribano Alvaro , Licht Adrian
Published: August 2021

Nonlinear co-integration is studied for score-driven models, using a new multivariate dynamic conditional score/generalized autoregressive score model. The model is namedt-QVARMA (quasi-vector autoregressive moving average model), which is a location model for the multivariatet-distribution. Int-QVARMA,I(0) and co-integratedI(1) components of the dependent variables are included. Fort-QVARMA, the conditions of the maximum likelihood estimator and impulse response functions (IRFs) are presented. A limiting special case oft-QVARMA, named Gaussian-QVARMA, is a Gaussian-VARMA specification withI(0) andI(1) components. As an empirical application, the US real gross domestic product growth, US inflation rate, and effective federal funds rate are studied for the period of 1954 Q3 to 2020 Q2. Statistical performance and predictive accuracy oft-QVARMA are superior to those of Gaussian-VAR. Estimates of the short-run IRF, long-run IRF, and total IRF impacts for the US data are reported.
Agriculture Subsidies: Unravelling the Linkages between the Amber Box and the Blue Box Support
Authors: Nedumpara James J. , Janardhan Sparsha , Bhattacharya Aparna
Published: August 2021

Domestic support disciplines under the Agreement on Agriculture are controversial, to say the least. The aggregate measurement of support (AMS) restricts Members’ policy space to provide product-specific support. The structural flaws in the determination of AMS further compel Members to explore alternatives. In contrast to the Amber Box, the Blue Box offers certain flexibilities for Members to exempt product-specific support from AMS calculation. The Blue Box reflects several elements which are seemingly typical to the Amber Box, except that it has certain production-limiting features. This article explores the legal bounds of the Blue Box measures, and its similarities and dissimilarities with the Amber Box. Towards this end, the article builds on a fresh legal understanding of the Blue Box based on its negotiating history and interpretative bounds, and also offers a fuller appreciation of market price support (MPS) and non-exempt direct payments under the Amber Box. While the calculation methodology for non-exempt direct payments bears a close resemblance to the calculation of MPS, the article argues that direct payment and MPS measures are fundamentally distinct types of product-specific support which makes the interchangeability of Blue and Amber Boxes seemingly difficult.
Smarter Medicine in der Radio-Onkologie
Authors: Zimmermann Frank , Eberhardt Anna-Lena , Förster Robert , Zwahlen Daniel R.
Published: August 2021

Zusammenfassung. Die modernen Verfahren in der Umsetzung einer Strahlentherapie, von der kritischen Indikationsstellung über die sorgfältige Therapieplanung bis hin zur präzisen Durchführung immer kürzerer Therapiesequenzen, haben vor allem in den häufigen, klinisch relevanten Einsatzgebieten (Mamma- und Prostatakarzinom; Knochenmetastasen) zu hohen lokalen Tumorkontrollen bei ausgezeichneter Lebensqualität geführt. So erfolgt eine sorgfältige vergleichende Betrachtung des Einsatzes systemischer Behandlungen gegenüber adjuvanten Strahlentherapien bei frühen Mammakarzinomen mit möglichem Verzicht auf eine Strahlenbehandlung, die rein lokale Strahlentherapie des vormaligen Tumorbettes im Rahmen eines brusterhaltenden Vorgehens und hypofraktionierte Strahlenbehandlungen der gesamten Brust bei höherem Risikoprofil mit Halbierung der Therapiezeiten gegenüber dem Vorgehen im letzten Jahrzehnt. Bei der primären Strahlentherapie des Prostatakarzinoms konnte die Therapiezeit halbiert werden und die aktuellen Entwicklungen zeigen in Richtung einer einwöchigen ambulanten Therapie bei lokal begrenztem Tumorleiden, unter Einsatz höchst präziser stereotaktischer Techniken und einer akkuraten Therapieplanung auf der Basis multifunktionaler Bildgebung. Beim ossär metastasierten Tumorleiden können mit identischen Techniken in vielen Fällen bereits radiochirurgische Einzeittherapien angeboten werden, die ein hohes analgetisches Potential besitzen und eine langanhaltende lokale Tumorkontrolle erzielen. Allen genannten Verfahren ist neben der ausgezeichneten Lebensqualität der behandelten Patientinnen und Patienten und einer deutlichen Verkürzung der Therapiesequenzen auch eine bessere Auslastung der Therapiegeräte und damit Entlastung des Gesundheitssystems bei geringerem Gerätebedarf in der Schweiz zu eigen.
Smarter Intensive Care Medicine: Choosing Wisely®, less is more, appropriate is better … and so what?
Authors: Fumeaux Thierry , Heise Antje , Balmer Martin , Lavina Luca
Published: August 2021

Zusammenfassung. Die Top-9-Liste der Schweizerischen Gesellschaft für Intensivmedizin (SGI) wurde 2017 veröffentlicht. Welchen Stand hat diese Initiative in Bezug auf ihre Umsetzung auf den Schweizer Intensivstationen? Welches sind ihre Auswirkungen auf die Patientenversorgung und auf die Kosten der Intensivmedizin? Welche evidenzbasierten, neueren Entwicklungen rechtfertigen eine Aktualisierung der Liste und welche Massnahmen sind erforderlich, um diese Initiative erfolgreich in den kommenden Jahren fortzusetzen? Der folgende Artikel gibt einen aktuellen Überblick über die «Choosing Wisely®»-Initiative der SGI.
Why Choose the Railway?
Authors: Duddin Keely S. E. , Raynes Benjamin
Published: August 2021

Abstract. Background: The impact of railway suicide in the United Kingdom is extensive, yet reasons for why people choose this method are not clearly understood and research into the examination of suicide notes in this area is limited. Aims: Our study aimed to utilize the unique access to suicide notes written by those who died by suicide on the railway so as to gain a greater understanding of why people chose this method. Method: Descriptive and thematic analysis was conducted on 75 suicide notes for those who had died by suicide on the UK railway between 2010 and 2016. Results: Demographic findings from the sample were largely consistent with railway UK data trends. Five main themes were identified as being significant: “certain and instant,” “impersonal and non-human,” “ability to be planned,” “a good death,” and “bereavement suicide.” Limitations: Findings are based on suicide note authors who died by suicide on the railway in the UK, as such generalizability may be limited. Conclusion: Findings suggest that people select the railway for their suicide for the following motives: perception of being instant and certain and viewed as a good death, ability to be planned, belief it causes less of a burden on loved ones (via the perception of the railway as impersonal), and a prior experience of it being fatal (via bereavement suicide). Key implications in relation to prevention strategies and future research are discussed.
Extracellular vesicle associated and soluble immune marker profiles of psychoneurological symptom clusters in men with prostate cancer: an exploratory study
Authors: Sass Dilorom , Saligan Leorey , Fitzgerald Wendy , Berger Ann M. , Torres Isaias , Barb Jennifer J. , Kupzyk Kevin , Margolis Leonid
Published: August 2021

Psychoneurological symptom clusters are co-occurring and interrelated physiological symptoms that may include cancer-related fatigue, pain, depressive symptoms, cognitive disturbances, and sleep disturbances. These symptoms are hypothesized to share a common systemic proinflammatory etiology. Thus, an investigation of systemic immune biomarkers is an important approach to test this hypothesis. Here, we investigated the associations between extracellular vesicle (EV)-associated and soluble cytokines with immune markers and symptom clusters in men with non-metastatic prostate cancer. This observational study included 40 men with non-metastatic prostate cancer at the start (T1) of external beam radiation therapy (EBRT) and 3 months post treatment (T2), as well as 20 men with non-metastatic prostate cancer on active surveillance (AS) seen at one time point. Collected questionnaires assessed patient-reported fatigue, sleep disturbances, depressive symptoms, and cognitive fatigue. In total, 45 soluble and EV-associated biomarkers in plasma were determined by multiplex assays. Principal component analysis (PCA) was used to identify psychoneurological symptom clusters for each study group and their time points. Bivariate correlation analysis was run for each identified PCA cluster with the concentrations of EV-associated and soluble cytokines and immune markers. Both EV-associated and soluble forms of RANTES significantly correlated with the symptom cluster for EBRT at T1, whereas, at T2, soluble IFNα2, IL-9, and IL-17 correlated with the corresponding symptom cluster. For the AS group, soluble survivin correlated with psychoneurological symptoms. Linking specific inflammatory cytokines with psychoneurological symptom clusters in men receiving prostate cancer treatment can enhance understanding of the underlying mechanisms of this phenomenon and aid in developing targeted interventions.
LncRNA SNHG17 regulates cell proliferation and invasion by targeting miR-338-3p/SOX4 axis in esophageal squamous cell carcinoma
Authors: Chen Wenhu , Wang Lifang , Li Xiaoyan , Zhao Changan , Shi Liang , Zhao Hongguang , Huang Chen
Published: August 2021

Small nucleolar RNA host gene 17 (SNHG17), a novel functional long noncoding RNA, has been demonstrated to play an essential role in the oncogenesis of several tumors. However, for esophageal squamous cell carcinoma (ESCC) the expression pattern and detailed function of SNHG17 are largely unknown. Hence, we conducted this study to explore potential roles and underlying oncogenic mechanisms for SNHG17 in ESCC progression. Results demonstrated SNHG17 to be markedly upregulated in ESCC. Knockdown of SNHG17 significantly suppressed ESCC cell proliferation, invasion, and epithelial–mesenchymal transition in vitro and tumor growth in vivo. Online database software analysis found miR-338-3p to interact with SNHG17 with the level of miR-338-3p negatively correlated with SNHG17 levels in ESCC samples. Further, miR-338-3p was found to directly target SRY-box transcription factor 4 (SOX4) in ESCC cells. Mechanistic analysis suggested that SNHG17 acts as an endogenous “sponge” competing with miR-338-3p to regulate SOX4, thereby promoting tumor progression. These results suggest that these molecular interactions may be potential therapeutic targets for ESCC.
Undecidability in quantum thermalization
Authors: Shiraishi Naoto , Matsumoto Keiji
Published: August 2021

The investigation of thermalization in isolated quantum many-body systems has a long history, dating back to the time of developing statistical mechanics. Most quantum many-body systems in nature are considered to thermalize, while some never achieve thermal equilibrium. The central problem is to clarify whether a given system thermalizes, which has been addressed previously, but not resolved. Here, we show that this problem is undecidable. The resulting undecidability even applies when the system is restricted to one-dimensional shift-invariant systems with nearest-neighbour interaction, and the initial state is a fixed product state. We construct a family of Hamiltonians encoding dynamics of a reversible universal Turing machine, where the fate of a relaxation process changes considerably depending on whether the Turing machine halts. Our result indicates that there is no general theorem, algorithm, or systematic procedure determining the presence or absence of thermalization in any given Hamiltonian.
Nonlinear shifts in infectious rust disease due to climate change
Authors: Dudney Joan , Willing Claire E. , Das Adrian J. , Latimer Andrew M. , Nesmith Jonathan C. B. , Battles John J.
Published: August 2021

Range shifts of infectious plant disease are expected under climate change. As plant diseases move, emergent abiotic-biotic interactions are predicted to modify their distributions, leading to unexpected changes in disease risk. Evidence of these complex range shifts due to climate change, however, remains largely speculative. Here, we combine a long-term study of the infectious tree disease, white pine blister rust, with a six-year field assessment of drought-disease interactions in the southern Sierra Nevada. We find that climate change between 1996 and 2016 moved the climate optimum of the disease into higher elevations. The nonlinear climate change-disease relationship contributed to an estimated 5.5 (4.4–6.6) percentage points (p.p.) decline in disease prevalence in arid regions and an estimated 6.8 (5.8–7.9) p.p. increase in colder regions. Though climate change likely expanded the suitable area for blister rust by 777.9 (1.0–1392.9) km2into previously inhospitable regions, the combination of host-pathogen and drought-disease interactions contributed to a substantial decrease (32.79%) in mean disease prevalence between surveys. Specifically, declining alternate host abundance suppressed infection probabilities at high elevations, even as climatic conditions became more suitable. Further, drought-disease interactions varied in strength and direction across an aridity gradient—likely decreasing infection risk at low elevations while simultaneously increasing infection risk at high elevations. These results highlight the critical role of aridity in modifying host-pathogen-drought interactions. Variation in aridity across topographic gradients can strongly mediate plant disease range shifts in response to climate change.
Identification of active catalysts for the acceptorless dehydrogenation of alcohols to carbonyls
Authors: Wang Tao , Sha Jin , Sabbe Maarten , Sautet Philippe , Pera-Titus Marc , Michel Carine
Published: August 2021

Acceptorless dehydrogenation into carbonyls and molecular hydrogen is an attractive strategy to valorize (biobased) alcohols. Using 2-octanol dehydrogenation as benchmark reaction in a continuous reactor, a library of metal-supported catalysts is tested to validate the predictive level of catalytic activity for combined DFT and micro-kinetic modeling. Based on a series of transition metals, scaling relations are determined as a function of two descriptors, i.e. the surface binding energies of atomic carbon and oxygen. Then, a volcano-shape relation based on both descriptors is derived, paving the way to further optimization of active catalysts. Evaluation of 294 diluted alloys but also a series of carbides and nitrides with the volcano map identified 12 promising candidates with potentially improved activity for alcohol dehydrogenation, which provides useful guidance for experimental catalyst design. Further screening identifies β-Mo2N and γ-Mo2N exposing mostly (001) and (100) facets as potential candidates for alcohol dehydrogenation.
Engineered whole cut meat-like tissue by the assembly of cell fibers using tendon-gel integrated bioprinting
Authors: Kang Dong-Hee , Louis Fiona , Liu Hao , Shimoda Hiroshi , Nishiyama Yasutaka , Nozawa Hajime , Kakitani Makoto , Takagi Daisuke , Kasa Daijiro , Nagamori Eiji , Irie Shinji , Kitano Shiro , Matsusaki Michiya
Published: August 2021

With the current interest in cultured meat, mammalian cell-based meat has mostly been unstructured. There is thus still a high demand for artificial steak-like meat. We demonstrate in vitro construction of engineered steak-like tissue assembled of three types of bovine cell fibers (muscle, fat, and vessel). Because actual meat is an aligned assembly of the fibers connected to the tendon for the actions of contraction and relaxation, tendon-gel integrated bioprinting was developed to construct tendon-like gels. In this study, a total of 72 fibers comprising 42 muscles, 28 adipose tissues, and 2 blood capillaries were constructed by tendon-gel integrated bioprinting and manually assembled to fabricate steak-like meat with a diameter of 5 mm and a length of 10 mm inspired by a meat cut. The developed tendon-gel integrated bioprinting here could be a promising technology for the fabrication of the desired types of steak-like cultured meats.
Deciphering ion transport and ATPase coupling in the intersubunit tunnel of KdpFABC
Authors: Silberberg Jakob M. , Corey Robin A. , Hielkema Lisa , Stock Charlott , Stansfeld Phillip J. , Paulino Cristina , Hänelt Inga
Published: August 2021

KdpFABC, a high-affinity K+ pump, combines the ion channel KdpA and the P-type ATPase KdpB to secure survival at K+ limitation. Here, we apply a combination of cryo-EM, biochemical assays, and MD simulations to illuminate the mechanisms underlying transport and the coupling to ATP hydrolysis. We show that ions are transported via an intersubunit tunnel through KdpA and KdpB. At the subunit interface, the tunnel is constricted by a phenylalanine, which, by polarized cation-π stacking, controls K+ entry into the canonical substrate binding site (CBS) of KdpB. Within the CBS, ATPase coupling is mediated by the charge distribution between an aspartate and a lysine. Interestingly, individual elements of the ion translocation mechanism of KdpFABC identified here are conserved among a wide variety of P-type ATPases from different families. This leads us to the hypothesis that KdpB might represent an early descendant of a common ancestor of cation pumps.
Inertial and viscous flywheel sensing of nanoparticles
Authors: Katsikis Georgios , Collis Jesse F. , Knudsen Scott M. , Agache Vincent , Sader John E. , Manalis Scott R.
Published: August 2021

Rotational dynamics often challenge physical intuition while enabling unique realizations, from the rotor of a gyroscope that maintains its orientation regardless of the outer gimbals, to a tennis racket that rotates around its handle when tossed face-up in the air. In the context of inertial sensing, which can measure mass with atomic precision, rotational dynamics are normally considered a complication hindering measurement interpretation. Here, we exploit the rotational dynamics of a microfluidic device to develop a modality in inertial sensing. Combining theory with experiments, we show that this modality measures the volume of a rigid particle while normally being insensitive to its density. Paradoxically, particle density only emerges when fluid viscosity becomes dominant over inertia. We explain this paradox via a viscosity-driven, hydrodynamic coupling between the fluid and the particle that activates the rotational inertia of the particle, converting it into a ‘viscous flywheel’. This modality now enables the simultaneous measurement of particle volume and mass in fluid, using a single, high-throughput measurement.
Global scenarios of resource and emission savings from material efficiency in residential buildings and cars
Authors: Pauliuk Stefan , Heeren Niko , Berrill Peter , Fishman Tomer , Nistad Andrea , Tu Qingshi , Wolfram Paul , Hertwich Edgar G.
Published: August 2021

Material production accounts for a quarter of global greenhouse gas (GHG) emissions. Resource-efficiency and circular-economy strategies, both industry and demand-focused, promise emission reductions through reducing material use, but detailed assessments of their GHG reduction potential are lacking. We present a global-scale analysis of material efficiency for passenger vehicles and residential buildings. We estimate future changes in material flows and energy use due to increased yields, light design, material substitution, extended service life, and increased service efficiency, reuse, and recycling. Together, these strategies can reduce cumulative global GHG emissions until 2050 by 20–52 Gt CO2-eq (residential buildings) and 13–26 Gt CO2e-eq (passenger vehicles), depending on policy assumptions. Next to energy efficiency and low-carbon energy supply, material efficiency is the third pillar of deep decarbonization for these sectors. For residential buildings, wood construction and reduced floorspace show the highest potential. For passenger vehicles, it is ride sharing and car sharing.
Differentiable sampling of molecular geometries with uncertainty-based adversarial attacks
Authors: Schwalbe-Koda Daniel , Tan Aik Rui , Gómez-Bombarelli Rafael
Published: August 2021

Neural network (NN) interatomic potentials provide fast prediction of potential energy surfaces, closely matching the accuracy of the electronic structure methods used to produce the training data. However, NN predictions are only reliable within well-learned training domains, and show volatile behavior when extrapolating. Uncertainty quantification methods can flag atomic configurations for which prediction confidence is low, but arriving at such uncertain regions requires expensive sampling of the NN phase space, often using atomistic simulations. Here, we exploit automatic differentiation to drive atomistic systems towards high-likelihood, high-uncertainty configurations without the need for molecular dynamics simulations. By performing adversarial attacks on an uncertainty metric, informative geometries that expand the training domain of NNs are sampled. When combined with an active learning loop, this approach bootstraps and improves NN potentials while decreasing the number of calls to the ground truth method. This efficiency is demonstrated on sampling of kinetic barriers, collective variables in molecules, and supramolecular chemistry in zeolite-molecule interactions, and can be extended to any NN potential architecture and materials system.
Subpicosecond metamagnetic phase transition in FeRh driven by non-equilibrium electron dynamics
Authors: Pressacco Federico , Sangalli Davide , Uhlíř Vojtěch , Kutnyakhov Dmytro , Arregi Jon Ander , Agustsson Steinn Ymir , Brenner Günter , Redlin Harald , Heber Michael , Vasilyev Dmitry , Demsar Jure , Schönhense Gerd , Gatti Matteo , Marini Andrea , Wurth Wilfried , Sirotti Fausto
Published: August 2021

Femtosecond light-induced phase transitions between different macroscopic orders provide the possibility to tune the functional properties of condensed matter on ultrafast timescales. In first-order phase transitions, transient non-equilibrium phases and inherent phase coexistence often preclude non-ambiguous detection of transition precursors and their temporal onset. Here, we present a study combining time-resolved photoelectron spectroscopy and ab-initio electron dynamics calculations elucidating the transient subpicosecond processes governing the photoinduced generation of ferromagnetic order in antiferromagnetic FeRh. The transient photoemission spectra are accounted for by assuming that not only the occupation of electronic states is modified during the photoexcitation process. Instead, the photo-generated non-thermal distribution of electrons modifies the electronic band structure. The ferromagnetic phase of FeRh, characterized by a minority band near the Fermi energy, is established 350 ± 30 fs after the laser excitation. Ab-initio calculations indicate that the phase transition is initiated by a photoinduced Rh-to-Fe charge transfer.
Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer
Authors: Liu Wen , Chakraborty Binita , Safi Rachid , Kazmin Dmitri , Chang Ching-yi , McDonnell Donald P.
Published: August 2021

Hypercholesterolemia and dyslipidemia are associated with an increased risk for many cancer types and with poor outcomes in patients with established disease. Whereas the mechanisms by which this occurs are multifactorial we determine that chronic exposure of cells to 27-hydroxycholesterol (27HC), an abundant circulating cholesterol metabolite, selects for cells that exhibit increased cellular uptake and/or lipid biosynthesis. These cells exhibit substantially increased tumorigenic and metastatic capacity. Notably, the metabolic stress imposed upon cells by the accumulated lipids requires sustained expression of GPX4, a negative regulator of ferroptotic cell death. We show that resistance to ferroptosis is a feature of metastatic cells and further demonstrate that GPX4 knockdown attenuates the enhanced tumorigenic and metastatic activity of 27HC resistant cells. These findings highlight the general importance of ferroptosis in tumor growth and metastasis and suggest that dyslipidemia/hypercholesterolemia impacts cancer pathogenesis by selecting for cells that are resistant to ferroptotic cell death.
A host–guest semibiological photosynthesis system coupling artificial and natural enzymes for solar alcohol splitting
Authors: Cai Junkai , Zhao Liang , He Cheng , Li Yanan , Duan Chunying
Published: August 2021

Development of a versatile, sustainable and efficient photosynthesis system that integrates intricate catalytic networks and energy modules at the same location is of considerable future value to energy transformation. In the present study, we develop a coenzyme-mediated supramolecular host-guest semibiological system that combines artificial and enzymatic catalysis for photocatalytic hydrogen evolution from alcohol dehydrogenation. This approach involves modification of the microenvironment of a dithiolene-embedded metal-organic cage to trap an organic dye and NADH molecule simultaneously, serving as a hydrogenase analogue to induce effective proton reduction inside the artificial host. This abiotic photocatalytic system is further embedded into the pocket of the alcohol dehydrogenase to couple enzymatic alcohol dehydrogenation. This host-guest approach allows in situ regeneration of NAD+/NADH couple to transfer protons and electrons between the two catalytic cycles, thereby paving a unique avenue for a synergic combination of abiotic and biotic synthetic sequences for photocatalytic fuel and chemical transformation.
A non-enzymatic, isothermal strand displacement and amplification assay for rapid detection of SARS-CoV-2 RNA
Authors: Mohammadniaei Mohsen , Zhang Ming , Ashley Jon , Christensen Ulf Bech , Friis-Hansen Lennart Jan , Gregersen Rasmus , Lisby Jan Gorm , Benfield Thomas Lars , Nielsen Finn Erland , Henning Rasmussen Jens , Pedersen Ellen Bøtker , Olinger Anne Christine Rye , Kolding Lærke Tørring , Naseri Maryam , Zheng Tao , Wang Wentao , Gorodkin Jan , Sun Yi
Published: August 2021

The current nucleic acid signal amplification methods for SARS-CoV-2 RNA detection heavily rely on the functions of biological enzymes which imposes stringent transportation and storage conditions, high cost and global supply shortages. Here, a non-enzymatic whole genome detection method based on a simple isothermal signal amplification approach is developed for rapid detection of SARS-CoV-2 RNA and potentially any types of nucleic acids regardless of their size. The assay, termed non-enzymatic isothermal strand displacement and amplification (NISDA), is able to quantify 10 RNA copies.µL−1. In 164 clinical oropharyngeal RNA samples, NISDA assay is 100 % specific, and it is 96.77% and 100% sensitive when setting up in the laboratory and hospital, respectively. The NISDA assay does not require RNA reverse-transcription step and is fast (<30 min), affordable, highly robust at room temperature (>1 month), isothermal (42 °C) and user-friendly, making it an excellent assay for broad-based testing.
Humans and other commonly used model organisms are resistant to cycloheximide-mediated biases in ribosome profiling experiments
Authors: Sharma Puneet , Wu Jie , Nilges Benedikt S. , Leidel Sebastian A.
Published: August 2021

Ribosome profiling measures genome-wide translation dynamics at sub-codon resolution. Cycloheximide (CHX), a widely used translation inhibitor to arrest ribosomes in these experiments, has been shown to induce biases in yeast, questioning its use. However, whether such biases are present in datasets of other organisms including humans is unknown. Here we compare different CHX-treatment conditions in human cells and yeast in parallel experiments using an optimized protocol. We find that human ribosomes are not susceptible to conformational restrictions by CHX, nor does it distort gene-level measurements of ribosome occupancy, measured decoding speed or the translational ramp. Furthermore, CHX-induced codon-specific biases on ribosome occupancy are not detectable in human cells or other model organisms. This shows that reported biases of CHX are species-specific and that CHX does not affect the outcome of ribosome profiling experiments in most settings. Our findings provide a solid framework to conduct and analyze ribosome profiling experiments.
PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain
Authors: Wen Maorong , Cao Yunlei , Wu Bin , Xiao Taoran , Cao Ruiyu , Wang Qian , Liu Xiwei , Xue Hongjuan , Yu Yang , Lin Jialing , Xu Chenqi , Xu Jie , OuYang Bo
Published: August 2021

The cytoplasmic domain of PD-L1 (PD-L1-CD) regulates PD-L1 degradation and stability through various mechanism, making it an attractive target for blocking PD-L1-related cancer signaling. Here, by using NMR and biochemical techniques we find that the membrane association of PD-L1-CD is mediated by electrostatic interactions between acidic phospholipids and basic residues in the N-terminal region. The absence of the acidic phospholipids and replacement of the basic residues with acidic residues abolish the membrane association. Moreover, the basic-to-acidic mutations also decrease the cellular abundance of PD-L1, implicating that the electrostatic interaction with the plasma membrane mediates the cellular levels of PD-L1. Interestingly, distinct from its reported function as an activator of AMPK in tumor cells, the type 2 diabetes drug metformin enhances the membrane dissociation of PD-L1-CD by disrupting the electrostatic interaction, thereby decreasing the cellular abundance of PD-L1. Collectively, our study reveals an unusual regulatory mechanism that controls the PD-L1 level in tumor cells, suggesting an alternative strategy to improve the efficacy of PD-L1-related immunotherapies.
Expanding the binding specificity for RNA recognition by a PUF domain
Authors: Zhou Wei , Melamed Daniel , Banyai Gabor , Meyer Cindy , Tuschl Thomas , Wickens Marvin , Cao Junyue , Fields Stanley
Published: August 2021

The ability to design a protein to bind specifically to a target RNA enables numerous applications, with the modular architecture of the PUF domain lending itself to new RNA-binding specificities. For each repeat of the Pumilio-1 PUF domain, we generate a library that contains the 8,000 possible combinations of amino acid substitutions at residues critical for RNA contact. We carry out yeast three-hybrid selections with each library against the RNA recognition sequence for Pumilio-1, with any possible base present at the position recognized by the randomized repeat. We use sequencing to score the binding of each variant, identifying many variants with highly repeat-specific interactions. From these data, we generate an RNA binding code specific to each repeat and base. We use this code to design PUF domains against 16 RNAs, and find that some of these domains recognize RNAs with two, three or four changes from the wild type sequence.