bluuebunny/crossref_metadata_2025 huggingface dataset:
On Constituents of the Periodic Layered Microstructure Developed in the Solid-State Reaction Between Zinc and Co2Si
Authors: Wojewoda-Budka J. , Wierzbicka-Miernik A. , Litynska-Dobrzynska L. , Korneva A. , Kodentsov A.
Published: May 2020

The composition and crystal structure of the constituents of the periodic layered microstructure developed during the solid-state reaction between Co2Si intermetallic and zinc at 390 °C were investigated using scanning electron microscopy, transmission electron microscopy, and electron-probe microanalysis. It was demonstrated that the periodic layered morphology generated in the reaction zone of the Co2Si/Zn diffusion couples consists of bands of in situ-formed precipitates of cubic CoSi intermetallic, embedded in a continuous matrix of Co-Zn-based hexagonal phase containing a small amount of silicon. It was suggested that the formation of the hexagonal intermetallic of the same crystal structure as the binary δ phase of the Co-Zn system can be attributed to the possible stabilizing effect of silicon: the δ-phase structure becomes stable in the ternary Co-Si-Zn system at 390 °C.
The Golem of Psychology and the Ecosystemic Epistemology
Authors: Tateo Luca
Published: May 2020

The old controversy about the epistemic status of psychological sciences is useless and sterile. Psychology is ether a hard science nor a soft science. It is an ecological life science, whose object is the whole system of co-developmental relations constituted by the presence of the organism in a given environment. After criticizing the positions of the traditional epistemic debate between hard and soft views of psychology, I propose a way to fundament the core concepts in the method of complementary negation, based on cogenetic logic. Then, I defend the need to develop a third way: an ecological epistemology of psychology.
Computation of effectiveness factor for methanol steam reforming over Cu/ZnO/Al2O3 catalyst pellet
Authors: Olatunde Abayomi O. , Olafadehan Olaosebikan A. , Usman Mohammed A.
Published: May 2020

A mathematical model was developed for a diffusion–reaction process in a spherical catalyst pellet contained in a heterogeneous packed bed reactor. The model developed was solved to predict the effectiveness factor and also to perform sensitivity analysis for steam reforming of methanol on Cu/ZnO/Al2O3 catalyst a source of hydrogen fuel. The method of orthogonal collocation was used to solve the resulting differential equation. At temperature below 473 K the effect on intra-particle diffusion limitation is reduced to the minimum indicated by the effectiveness factor being almost equal to one but as the temperature increases above 473 K there is considerable increase in the diffusion limitation effect. The effects of thermal conductivity, diffusion coefficient, catalyst size and surface temperature on effectiveness factor for the reaction process were also considered. Result indicates that catalyst size of $$1.623\,\, \times \,\,10^{ - 4}$$1.623×10-4 m eliminates the effect of intra-particle diffusion resistance in the pellet. The variation of effectiveness factor with Thiele modulus, showing the asymptotic values, using power law and Langmuir–Hinshelwood–Hougen–Watson (LHHW) kinetics, was predicted. The two reaction kinetics had almost the same magnitude of effectiveness factor at different Thiele modulus which indicates that they can adequately predict the reaction process.
Reducing plagiarism through academic misconduct education
Authors: Perkins Mike , Gezgin Ulas Basar , Roe Jasper
Published: May 2020

Although there is much discussion exploring the potential causes of plagiarism, there is limited research available which provides evidence as to the academic interventions which may help reduce this. This paper discusses a bespoke English for Academic Purposes (EAP) programme introduced at the university level, aimed at improving the academic writing standards of students, reducing plagiarism, and detecting cases of contract cheating. Results from 12 semesters of academic misconduct data (n = 12,937) demonstrate a 37.01% reduction in instances of detected plagiarism following the intervention, but due to limited data, cannot demonstrate a direct impact on reducing detected rates of contract cheating. The results also show a lower than expected proportion of plagiarised assignments (3.46%) among submissions.
The Implications of the COVID-19 Pandemic on Trade
Authors: CARREÑO Ignacio , DOLLE Tobias , MEDINA Lourdes , BRANDENBURGER Moritz
Published: May 2020

On 17 March 2020, the President of the European Council, Charles Michel, and the President of the European Commission (hereinafter, Commission), Ursula von der Leyen, announced further European Union (EU) actions in response to the COVID-19 outbreak. Since the pandemic reached Europe, the EU has adopted a number of trade-related measures, including the issuance of guidelines for national border management, as well as export authorisation requirements. On 14 March 2020, the Commission adopted “Commission Implementing Regulation (EU) 2020/402 of 14 March 2020 making the exportation of certain products subject to the production of an export authorisation”, temporarily restricting exports of “personal protective equipment” to destinations outside of the EU. On 14 April 2020, the Commission announced that it would narrow down export authorisation requirements to protective masks only and extend the geographical and humanitarian exemptions. Governments around the world have been implementing trade-related measures in response to the COVID-19 pandemic, some trade restrictive, but a number of countries have also called for the elimination of export controls and restrictions on essential goods. As the greater implications of the COVID-19 pandemic on trade are still difficult to assess, the emergency measures taken by affected countries already require legal scrutiny. At the same time, it must be noted that, as noted above for the EU measures, measures around the world are subject to change dynamically in view of the evolution of the pandemic.
Leadership concepts in manufacturing environments: A brief historical review and conclusion with recommendations for education and training of I-O psychologists
Authors: Tinker-Walker Karen A. , Walker Jimmy D.
Published: May 2020

Viewing production-line workers from a historical standpoint, the attention on manufacturing in the 19th and into the 20th centuries was on production (Fifelski, 2014) and production-oriented leadership style, in contrast to employee-oriented leadership style (Likert, 1961; see also Kosicek, Soni, Sandbothe, & Slack, 2012).Around the turn of the 20th century, changes took place, and it appears as if two different approaches were taken in manufacturing environments: research–practitioner-based leadership approaches and management-based leadership approaches; the latter approach is less a leadership style and more a social management philosophy em+phasizing business operation (Vitolla, Rubino, & Garzoni, 2017). This review should bring awareness that industrial and organizational (I-O) psychologists once took on the lead to major successes that arose from work in manufacturing companies; however, today there is hardly any contribution by I-O psychologists to the manufacturing sector.
How Right-Leaning Media Coverage of COVID-19 Facilitated the Spread of Misinformation in the Early Stages of the Pandemic in the U.S.
Authors: Motta Matt , Stecula Dominik , Farhart Christina
Published: May 2020

We have yet to know the ultimate global impact of the novel coronavirus pandemic. However, we do know that delays, denials and misinformation about COVID-19 have exacerbated its spread and slowed pandemic response, particularly in the U.S. (e.g., Abutaleb et al., 2020).
THE LONG GOODBYE: PROBLEMATIC POTTERY AND PILGRIMAGE AT CAHAL PECH, BELIZE
Authors: Aimers James J. , Awe Jaime J.
Published: May 2020

Investigations in the site core of Cahal Pech have recovered a range of data reflecting Terminal Classic Maya activity at this Belize Valley site. The materials, which were recovered in a tomb, a burial, and in epicentral plaza deposits, include a diverse assemblage of cultural remains including whole and partial vessels, projectile points, obsidian blade fragments, deer antlers, figurines, pottery flutes, spindle whorls, and jade beads. Similar deposits at other Maya sites in western Belize have been interpreted as evidence forde factorefuse or rapid abandonment. Contextual analyses of the Cahal Pech data suggest that the deposits are more likely associated with post-abandonment activity such as pilgrimage from the still-occupied periphery of the site.
Comparison of three different statistical approaches (non-linear least-squares regression, survival analysis and Bayesian inference) in their usefulness for estimating hydrothermal time models of seed germination
Authors: Moltchanova Elena , Sharifiamina Shirin , Moot Derrick J. , Shayanfar Ali , Bloomberg Mark
Published: May 2020

Hydrothermal time (HTT) models describe the time course of seed germination for a population of seeds under specific temperature and water potential conditions. The parameters of the HTT model are usually estimated using either a linear regression, non-linear least squares estimation or a generalized linear regression model. There are problems with these approaches, including loss of information, and censoring and lack of independence in the germination data. Model estimation may require optimization, and this can have a heavy computational burden. Here, we compare non-linear regression with survival and Bayesian methods, to estimate HTT models for germination of two clover species. All three methods estimated similar HTT model parameters with similar root mean squared errors. However, the Bayesian approach allowed (1) efficient estimation of model parameters without the need for computation-intensive methods and (2) easy comparison of HTT parameters for the two clover species. HTT models that accounted for a species effect were superior to those that did not. Inspection of credibility intervals and estimated posterior distributions for the Bayesian HTT model shows that it is credible that most HTT model parameters were different for the two clover species, and these differences were consistent with known biological differences between species in their germination behaviour.
Frequently asked questions regarding SARS-CoV-2 in cancer patients—recommendations for clinicians caring for patients with malignant diseases
Authors:   EHA Infectious Disease Scientific Working Group, von Lilienfeld-Toal Marie , Vehreschild Jörg Janne , Cornely Oliver , Pagano Livio , Compagno Francesca , Hirsch Hans H.
Published: May 2020

Since early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required. Here, we provide recommendations for the management of patients with malignant disease in the times of COVID-19. These recommendations were prepared by an international panel of experts and then consented by the EHA Scientific Working Group on Infection in Hematology. The primary aim is to enable clinicians to provide optimal cancer care as safely as possible, since the most important protection for patients with malignant disease is the best-possible control of the underlying disease.
Postprandial blood glucose response: does the glycaemic index (GI) value matter even in the low GI range?
Authors: Kaur Bhupinder , Koh Melvin , Ponnalagu Shalini , Henry Christiani Jeyakumar
Published: May 2020

A growing body of research over the last decades has shown that diets based on the low glycaemic index (GI) foods reduce the risk of developing diabetes and improve blood glucose control in people with diabetes. The range of inflexion on the glycaemic response of low GI (LGI) foods is an interesting observation that has not been studied by many. LGI 1 (GI 54 ± 3.3) biscuit was formulated using a basic formulation while the LGI 2 (23.8 ± 3.3) biscuits was a modification of LGI 1 recipe, formulated with the inclusion of functional ingredients. Biscuits were formulated to be iso-caloric (kcal/100 g: 521 ± 12). Each participant consumed identical standard meals for lunch and dinner. Biscuits were consumed as breakfast and mid-afternoon snack. Using a randomized, controlled, crossover study, 13 males [(means ± SD) age: 25.3 ± 1.0 years, BMI 21.6 ± 0.5 kg/m2, fasting blood glucose 4.7 ± 0.1 mmol/L] wore continuous glucose monitoring systems (CGMS™) for 3 days for each test session. The postprandial glycaemic response and insulin response were compared within participants. Total iAUC for breakfast and standard dinner were significantly lower for LGI 2 treatment (p < 0.05) than LGI 1 treatment. Second-meal glucose tolerance was observed at the dinner meal. The overall iAUC insulin response over 180 min was significantly lower for LGI 2 biscuits (p = 0.01). The postprandial glycaemic response of two types of biscuits that fall within the low GI classification (GI 24 and 54) differed with LGI 2 biscuits (GI 24) showing a more suppressed postprandial glycaemic response. Our study shows that even within the low GI range, the GI value matters in influencing postprandial glucose.
PROMPT intervention for children with severe speech motor delay: a randomized control trial
Authors: Namasivayam Aravind K. , Huynh Anna , Granata Francesca , Law Vina , van Lieshout Pascal
Published: May 2020

Background

Currently, there is limited information on the intervention efficacy for children with speech motor delay (SMD). This randomized control trial (RCT) study examined the effectiveness of Prompts for Restructuring Oral Muscular Phonetic Targets (PROMPT) intervention to improve the outcomes in children with SMD. We hypothesized that children with SMD receiving PROMPT intervention would improve more in the measured outcomes than those waitlisted and receiving home training.

Methods

Using a two-arm, parallel group, RCT, 49 children with SMD were allocated to either an intervention group (N = 24) that received 45 min of PROMPT intervention two times a week for 10 weeks or were waitlisted for the same duration and received only home training instructions (N = 25). Outcome measures for speech motor control, articulation, speech intelligibility (word and sentence levels), and functional communication were assessed at baseline and at a 10-week follow-up.

Results

PROMPT intervention was associated with notable improvements in speech motor control, speech articulation, and word-level speech intelligibility. Intervention allocation yielded weak improvements in sentence-level speech intelligibility and functional communication.

Conclusions

PROMPT intervention is a clinically effective intervention approach for children with SMD.

Impact

Currently, there is limited information on the intervention efficacy for children with SMD.

We report on the findings of a phase III intervention efficacy study on children with SMD using an RCT design.

PROMPT intervention is a clinically effective intervention approach for children with SMD.

Results of the study will be fundamental to the delivery of effective services for this population.

These findings may facilitate the development of an evidence-based care pathway for children with severe speech sound disorders.
A novel neurodegenerative spectrum disorder in patients with MLKL deficiency
Authors: Faergeman Soren L. , Evans Hayley , Attfield Kathrine E. , Desel Christiane , Kuttikkatte Subita Balaram , Sommerlund Mette , Jensen Lise Torp , Frokiaer Jorgen , Friese Manuel A. , Matthews Paul M. , Luchtenborg Christian , Brügger Britta , Oturai Annette Bang , Dendrou Calliope A. , Fugger Lars
Published: May 2020

Mixed lineage kinase domain-like (MLKL) is the main executor of necroptosis, an inflammatory form of programmed cell death. Necroptosis is implicated in combating infections, but also in contributing to numerous other clinical conditions, including cardiovascular diseases and neurodegenerative disorders. Inhibition of necroptosis is therefore of therapeutic interest. Here we report two siblings both of whom over the course of 35 years developed a similar progressive, neurodegenerative spectrum disorder characterized by paresis, ataxia and dysarthria. Magnetic resonance imaging of their central nervous system (CNS) revealed severe global cerebral volume loss and atrophy of the cerebellum and brainstem. These brothers are homozygous for a rare haplotype identified by whole genome sequencing carrying a frameshift variant in MLKL, as well as an in-frame deletion of one amino acid in the adjacent fatty acid 2-hydroxylase (FA2H) gene. Functional studies of patient-derived primary cells demonstrated that the variant in MLKL leads to a deficiency of MLKL protein resulting in impairment of necroptosis. Conversely, shotgun lipidomic analysis of the variant in FA2H shows no impact on either the abundance or the enzymatic activity of the encoded hydroxylase. To our knowledge, this is the first report of complete necroptosis deficiency in humans. The findings may suggest that impaired necroptosis is a novel mechanism of neurodegeneration, promoting a disorder that shares some clinical features with primary progressive multiple sclerosis (PPMS) and other neurodegenerative diseases. Importantly, the necroptotic deficiency does not cause symptoms outside the nervous system, nor does it confer susceptibility to infections. Given the current interest in pharmacological inhibition of necroptosis by targeting MLKL and its associated pathways, this strategy should be developed with caution, with careful consideration of the possible development of adverse neurological effects.
Regulation of TFEB activity and its potential as a therapeutic target against kidney diseases
Authors: Zhang Weihuang , Li Xiaoyu , Wang Shujun , Chen Yanse , Liu Huafeng
Published: May 2020

The transcription factor EB (TFEB) regulates the expression of target genes bearing the Coordinated Lysosomal Expression and Regulation (CLEAR) motif, thereby modulating autophagy and lysosomal biogenesis. Furthermore, TFEB can bind to the promoter of autophagy-associated genes and induce the formation of autophagosomes, autophagosome–lysosome fusion, and lysosomal cargo degradation. An increasing number of studies have shown that TFEB stimulates the intracellular clearance of pathogenic factors by enhancing autophagy and lysosomal function in multiple kidney diseases, such as cystinosis, acute kidney injury, and diabetic nephropathy. Taken together, this highlights the importance of developing novel therapeutic strategies against kidney diseases based on TFEB regulation. In this review, we present an overview of the current data on TFEB and its implication in kidney disease.
Novel fluorinated polycationic delivery of anti-VEGF siRNA for tumor therapy
Authors: Yuan Zihan , Guo Xiaoshuang , Wei Minyan , Xu Yang , Fang Zhiwei , Feng Yun , Yuan Wei-En
Published: May 2020

Small-interfering RNA (siRNA) can specifically silence disease gene expression, bringing hope for the effective treatment of gene-related diseases. However, its use in vivo is limited due to the lack of efficient carriers. Therefore, it is necessary to construct carriers with high efficiency, low toxicity and serum stability. As a promising polycation carrier, polyethylenimine (PEI) can be further modified with a fluorine-containing alkyl chain that brings hydrophobic and oleophobic characteristics to its surface. In this study, low molecular weight PEI 1.8 kDa was selected and fluorinated through an anhydride reaction, and the product was named PEIF. In vitro experiments have shown that PEIF/siRNA polyplexes have suitable and stable particle size and potential, compress nucleic acids at a very low w/w ratio, and have the ability to effectively silence specific genes with low cytotoxicity. Compared with the polyplexes prepared using PEI 25 kDa, the PEIF/siRNA polyplexes were more stable in serum, showed a better antiangiogenic ability in in vivo experiments, and had a better tumor inhibition effect. The above results indicate that fluoropolymers based on the fluorine effect have great potential as gene delivery carriers for tumor therapy.
Breaking translational symmetry via polymer chain overcrowding in molecular bottlebrush crystallization
Authors: Qi Hao , Liu Xiting , Henn Daniel M. , Mei Shan , Staub Mark C. , Zhao Bin , Li Christopher Y.
Published: May 2020

One of the fundamental laws in crystallization is translational symmetry, which accounts for the profound shapes observed in natural mineral crystals and snowflakes. Herein, we report on the spontaneous formation of spherical hollow crystals with broken translational symmetry in crystalline molecular bottlebrush (mBB) polymers. The unique structure is named as mBB crystalsome (mBBC), highlighting its similarity to the classical molecular vesicles. Fluorescence resonance energy transfer (FRET) experiments show that the mBBC formation is driven by local chain overcrowding-induced asymmetric lamella bending, which is further confirmed by correlating crystalsome size with crystallization temperature and mBBʼs side chain grafting density. Our study unravels a new principle of spontaneous translational symmetry breaking, providing a general route towards designing versatile nanostructures.
Slip bursts during coalescence of slow slip events in Cascadia
Authors: Bletery Quentin , Nocquet Jean-Mathieu
Published: May 2020

Both laboratory experiments and dynamic simulations suggest that earthquakes can be preceded by a precursory phase of slow slip. Observing processes leading to an acceleration or spreading of slow slip along faults is therefore key to understand the dynamics potentially leading to seismic ruptures. Here, we use continuous GPS measurements of the ground displacement to image the daily slip along the fault beneath Vancouver Island during a slow slip event in 2013. We image the coalescence of three originally distinct slow slip fronts merging together. We show that during coalescence phases lasting for 2 to 5 days, the rate of energy (moment) release significantly increases. This observation supports the view proposed by theoretical and experimental studies that the coalescence of slow slip fronts is a possible mechanism for initiating earthquakes.
Lipid-protein interactions modulate the conformational equilibrium of a potassium channel
Authors: Gu Ruo-Xu , de Groot Bert L.
Published: May 2020

Cell membranes actively participate in the regulation of protein structure and function. In this work, we conduct molecular dynamics simulations to investigate how different membrane environments affect protein structure and function in the case of MthK, a potassium channel. We observe different ion permeation rates of MthK in membranes with different properties, and ascribe them to a shift of the conformational equilibrium between two states of the channel that differ according to whether a transmembrane helix has a kink. Further investigations indicate that two key residues in the kink region mediate a crosstalk between two gates at the selectivity filter and the central cavity, respectively. Opening of one gate eventually leads to closure of the other. Our simulations provide an atomistic model of how lipid-protein interactions affect the conformational equilibrium of a membrane protein. The gating mechanism revealed for MthK may also apply to other potassium channels.
Promoting H2O2 production via 2-electron oxygen reduction by coordinating partially oxidized Pd with defect carbon
Authors: Chang Qiaowan , Zhang Pu , Mostaghimi Amir Hassan Bagherzadeh , Zhao Xueru , Denny Steven R. , Lee Ji Hoon , Gao Hongpeng , Zhang Ying , Xin Huolin L. , Siahrostami Samira , Chen Jingguang G. , Chen Zheng
Published: May 2020

Electrochemical synthesis of H2O2through a selective two-electron (2e−) oxygen reduction reaction (ORR) is an attractive alternative to the industrial anthraquinone oxidation method, as it allows decentralized H2O2production. Herein, we report that the synergistic interaction between partially oxidized palladium (Pdδ+) and oxygen-functionalized carbon can promote 2e−ORR in acidic electrolytes. An electrocatalyst synthesized by solution deposition of amorphous Pdδ+clusters (Pd3δ+and Pd4δ+) onto mildly oxidized carbon nanotubes (Pdδ+-OCNT) shows nearly 100% selectivity toward H2O2and a positive shift of ORR onset potential by ~320 mV compared with the OCNT substrate. A high mass activity (1.946 A mg−1at 0.45 V) of Pdδ+-OCNT is achieved. Extended X-ray absorption fine structure characterization and density functional theory calculations suggest that the interaction between Pd clusters and the nearby oxygen-containing functional groups is key for the high selectivity and activity for 2e−ORR.
Stability and nuclear localization of yeast telomerase depend on protein components of RNase P/MRP
Authors: Garcia P. Daniela , Leach Robert W. , Wadsworth Gable M. , Choudhary Krishna , Li Hua , Aviran Sharon , Kim Harold D. , Zakian Virginia A.
Published: May 2020

RNase P and MRP are highly conserved, multi-protein/RNA complexes with essential roles in processing ribosomal and tRNAs. Three proteins found in both complexes, Pop1, Pop6, and Pop7 are also telomerase-associated. Here, we determine how temperature sensitive POP1 and POP6 alleles affect yeast telomerase. At permissive temperatures, mutant Pop1/6 have little or no effect on cell growth, global protein levels, the abundance of Est1 and Est2 (telomerase proteins), and the processing of TLC1 (telomerase RNA). However, in pop mutants, TLC1 is more abundant, telomeres are short, and TLC1 accumulates in the cytoplasm. Although Est1/2 binding to TLC1 occurs at normal levels, Est1 (and hence Est3) binding is highly unstable. We propose that Pop-mediated stabilization of Est1 binding to TLC1 is a pre-requisite for formation and nuclear localization of the telomerase holoenzyme. Furthermore, Pop proteins affect TLC1 and the RNA subunits of RNase P/MRP in very different ways.
SYNERGISTIC ON AUXIN AND CYTOKININ 1 positively regulates growth and attenuates soil pathogen resistance
Authors: Hurný Andrej , Cuesta Candela , Cavallari Nicola , Ötvös Krisztina , Duclercq Jerome , Dokládal Ladislav , Montesinos Juan Carlos , Gallemí Marçal , Semerádová Hana , Rauter Thomas , Stenzel Irene , Persiau Geert , Benade Freia , Bhalearo Rishikesh , Sýkorová Eva , Gorzsás András , Sechet Julien , Mouille Gregory , Heilmann Ingo , De Jaeger Geert , Ludwig-Müller Jutta , Benková Eva
Published: May 2020

Plants as non-mobile organisms constantly integrate varying environmental signals to flexibly adapt their growth and development. Local fluctuations in water and nutrient availability, sudden changes in temperature or other abiotic and biotic stresses can trigger changes in the growth of plant organs. Multiple mutually interconnected hormonal signaling cascades act as essential endogenous translators of these exogenous signals in the adaptive responses of plants. Although the molecular backbones of hormone transduction pathways have been identified, the mechanisms underlying their interactions are largely unknown. Here, using genome wide transcriptome profiling we identify an auxin and cytokinin cross-talk component; SYNERGISTIC ON AUXIN AND CYTOKININ 1 (SYAC1), whose expression in roots is strictly dependent on both of these hormonal pathways. We show that SYAC1 is a regulator of secretory pathway, whose enhanced activity interferes with deposition of cell wall components and can fine-tune organ growth and sensitivity to soil pathogens.
Critical slowing down as a biomarker for seizure susceptibility
Authors: Maturana Matias I. , Meisel Christian , Dell Katrina , Karoly Philippa J. , D’Souza Wendyl , Grayden David B. , Burkitt Anthony N. , Jiruska Premysl , Kudlacek Jan , Hlinka Jaroslav , Cook Mark J. , Kuhlmann Levin , Freestone Dean R.
Published: May 2020

The human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system suggest that prior to a seizure, recorded brain signals may exhibit critical slowing down, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we monitored key signatures of critical slowing down prior to seizures. The metrics used to detect critical slowing down fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing down is a reliable indicator that could be used in seizure forecasting algorithms.
Lipid metabolism adaptations are reduced in human compared to murine Schwann cells following injury
Authors: Meyer zu Reckendorf Sofia , Brand Christine , Pedro Maria T. , Hegler Jutta , Schilling Corinna S. , Lerner Raissa , Bindila Laura , Antoniadis Gregor , Knöll Bernd
Published: May 2020

Mammals differ in their regeneration potential after traumatic injury, which might be caused by species-specific regeneration programs. Here, we compared murine and human Schwann cell (SC) response to injury and developed an ex vivo injury model employing surgery-derived human sural nerves. Transcriptomic and lipid metabolism analysis of murine SCs following injury of sural nerves revealed down-regulation of lipogenic genes and regulator of lipid metabolism, including Pparg (peroxisome proliferator-activated receptor gamma) and S1P (sphingosine-1-phosphate). Human SCs failed to induce similar adaptations following ex vivo nerve injury. Pharmacological PPARg and S1P stimulation in mice resulted in up-regulation of lipid gene expression, suggesting a role in SCs switching towards a myelinating state. Altogether, our results suggest that murine SC switching towards a repair state is accompanied by transcriptome and lipidome adaptations, which are reduced in humans.
Mega macromolecules as single molecule lubricants for hard and soft surfaces
Authors: Anilkumar Parambath , Lawson Taylor B. , Abbina Srinivas , Mäkelä Janne T. A. , Sabatelle Robert C. , Takeuchi Lily E. , Snyder Brian D. , Grinstaff Mark W. , Kizhakkedathu Jayachandran N.
Published: May 2020

A longstanding goal in science and engineering is to mimic the size, structure, and functionality present in biology with synthetic analogs. Today, synthetic globular polymers of several million molecular weight are unknown, and, yet, these structures are expected to exhibit unanticipated properties due to their size, compactness, and low inter-chain interactions. Here we report the gram-scale synthesis of dendritic polymers, mega hyperbranched polyglycerols (mega HPGs), in million daltons. The mega HPGs are highly water soluble, soft, nanometer-scale single polymer particles that exhibit low intrinsic viscosities. Further, the mega HPGs are lubricants acting as interposed single molecule ball bearings to reduce the coefficient of friction between both hard and soft natural surfaces in a size dependent manner. We attribute this result to their globular and single particle nature together with its exceptional hydration. Collectively, these results set the stage for new opportunities in the design, synthesis, and evaluation of mega polymers.
SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease
Authors: Kim So Ra , Lee Sang-Guk , Kim Soo Hyun , Kim Jin Hee , Choi Eunhye , Cho Wonhee , Rim John Hoon , Hwang Inhwa , Lee Chan Joo , Lee Minyoung , Oh Chang-Myung , Jeon Justin Y. , Gee Heon Yung , Kim Jeong-Ho , Lee Byung-Wan , Kang Eun Seok , Cha Bong-Soo , Lee Myung-Shik , Yu Je-Wook , Cho Jin Won , Kim Jung-Sun , Lee Yong-ho
Published: May 2020

Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor’s glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
Ultrastructural visualization of 3D chromatin folding using volume electron microscopy and DNA in situ hybridization
Authors: Trzaskoma Paweł , Ruszczycki Błażej , Lee Byoungkoo , Pels Katarzyna K. , Krawczyk Katarzyna , Bokota Grzegorz , Szczepankiewicz Andrzej A. , Aaron Jesse , Walczak Agnieszka , Śliwińska Małgorzata A. , Magalska Adriana , Kadlof Michal , Wolny Artur , Parteka Zofia , Arabasz Sebastian , Kiss-Arabasz Magdalena , Plewczyński Dariusz , Ruan Yijun , Wilczyński Grzegorz M.
Published: May 2020

The human genome is extensively folded into 3-dimensional organization. However, the detailed 3D chromatin folding structures have not been fully visualized due to the lack of robust and ultra-resolution imaging capability. Here, we report the development of an electron microscopy method that combines serial block-face scanning electron microscopy with in situ hybridization (3D-EMISH) to visualize 3D chromatin folding at targeted genomic regions with ultra-resolution (5 × 5 × 30 nm in xyz dimensions) that is superior to the current super-resolution by fluorescence light microscopy. We apply 3D-EMISH to human lymphoblastoid cells at a 1.7 Mb segment of the genome and visualize a large number of distinctive 3D chromatin folding structures in ultra-resolution. We further quantitatively characterize the reconstituted chromatin folding structures by identifying sub-domains, and uncover a high level heterogeneity of chromatin folding ultrastructures in individual nuclei, suggestive of extensive dynamic fluidity in 3D chromatin states.
Attention amplifies neural representations of changes in sensory input at the expense of perceptual accuracy
Authors: Mehrpour Vahid , Martinez-Trujillo Julio C. , Treue Stefan
Published: May 2020

Attention enhances the neural representations of behaviorally relevant stimuli, typically by a push–pull increase of the neuronal response gain to attended vs. unattended stimuli. This selectively improves perception and consequently behavioral performance. However, to enhance the detectability of stimulus changes, attention might also distort neural representations, compromising accurate stimulus representation. We test this hypothesis by recording neural responses in the visual cortex of rhesus monkeys during a motion direction change detection task. We find that attention indeed amplifies the neural representation of direction changes, beyond a similar effect of adaptation. We further show that humans overestimate such direction changes, providing a perceptual correlate of our neurophysiological observations. Our results demonstrate that attention distorts the neural representations of abrupt sensory changes and consequently perceptual accuracy. This likely represents an evolutionary adaptive mechanism that allows sensory systems to flexibly forgo accurate representation of stimulus features to improve the encoding of stimulus change.
Taking a snapshot of the triplet excited state of an OLED organometallic luminophore using X-rays
Authors: Smolentsev Grigory , Milne Christopher J. , Guda Alexander , Haldrup Kristoffer , Szlachetko Jakub , Azzaroli Nicolo , Cirelli Claudio , Knopp Gregor , Bohinc Rok , Menzi Samuel , Pamfilidis Georgios , Gashi Dardan , Beck Martin , Mozzanica Aldo , James Daniel , Bacellar Camila , Mancini Giulia F. , Tereshchenko Andrei , Shapovalov Victor , Kwiatek Wojciech M. , Czapla-Masztafiak Joanna , Cannizzo Andrea , Gazzetto Michela , Sander Mathias , Levantino Matteo , Kabanova Victoria , Rychagova Elena , Ketkov Sergey , Olaru Marian , Beckmann Jens , Vogt Matthias
Published: May 2020

OLED technology beyond small or expensive devices requires light-emitters, luminophores, based on earth-abundant elements. Understanding and experimental verification of charge transfer in luminophores are needed for this development. An organometallic multicore Cu complex comprising Cu–C and Cu–P bonds represents an underexplored type of luminophore. To investigate the charge transfer and structural rearrangements in this material, we apply complementary pump-probe X-ray techniques: absorption, emission, and scattering including pump-probe measurements at the X-ray free-electron laser SwissFEL. We find that the excitation leads to charge movement from C- and P- coordinated Cu sites and from the phosphorus atoms to phenyl rings; the Cu core slightly rearranges with 0.05 Å increase of the shortest Cu–Cu distance. The use of a Cu cluster bonded to the ligands through C and P atoms is an efficient way to keep structural rigidity of luminophores. Obtained data can be used to verify computational methods for the development of luminophores.
Accelerating invasion potential of disease vector Aedes aegypti under climate change
Authors: Iwamura Takuya , Guzman-Holst Adriana , Murray Kris A.
Published: May 2020

Vector-borne diseases remain a major contributor to the global burden of disease, while climate change is expected to exacerbate their risk. Characterising vector development rate and its spatio-temporal variation under climate change is central to assessing the changing basis of human disease risk. We develop a mechanistic phenology model and apply it to Aedes aegypti, an invasive mosquito vector for arboviruses (e.g. dengue, zika and yellow fever). The model predicts the number of life-cycle completions (LCC) for a given location per unit time based on empirically derived biophysical responses to environmental conditions. Results suggest that the world became ~1.5% more suitable per decade for the development of Ae. aegypti during 1950–2000, while this trend is predicted to accelerate to 3.2–4.4% per decade by 2050. Invasion fronts in North America and China are projected to accelerate from ~2 to 6 km/yr by 2050. An increase in peak LCC combined with extended periods suitable for mosquito development is simulated to accelerate the vector’s global invasion potential.
Molecular mechanism of light-driven sodium pumping
Authors: Kovalev Kirill , Astashkin Roman , Gushchin Ivan , Orekhov Philipp , Volkov Dmytro , Zinovev Egor , Marin Egor , Rulev Maksim , Alekseev Alexey , Royant Antoine , Carpentier Philippe , Vaganova Svetlana , Zabelskii Dmitrii , Baeken Christian , Sergeev Ilya , Balandin Taras , Bourenkov Gleb , Carpena Xavier , Boer Roeland , Maliar Nina , Borshchevskiy Valentin , Büldt Georg , Bamberg Ernst , Gordeliy Valentin
Published: May 2020

The light-driven sodium-pumping rhodopsin KR2 from Krokinobacter eikastus is the only non-proton cation active transporter with demonstrated potential for optogenetics. However, the existing structural data on KR2 correspond exclusively to its ground state, and show no sodium inside the protein, which hampers the understanding of sodium-pumping mechanism. Here we present crystal structure of the O-intermediate of the physiologically relevant pentameric form of KR2 at the resolution of 2.1 Å, revealing a sodium ion near the retinal Schiff base, coordinated by N112 and D116 of the characteristic NDQ triad. We also obtained crystal structures of D116N and H30A variants, conducted metadynamics simulations and measured pumping activities of putative pathway mutants to demonstrate that sodium release likely proceeds alongside Q78 towards the structural sodium ion bound between KR2 protomers. Our findings highlight the importance of pentameric assembly for sodium pump function, and may be used for rational engineering of enhanced optogenetic tools.
A deep-learned skin sensor decoding the epicentral human motions
Authors: Kim Kyun Kyu , Ha InHo , Kim Min , Choi Joonhwa , Won Phillip , Jo Sungho , Ko Seung Hwan
Published: May 2020

State monitoring of the complex system needs a large number of sensors. Especially, studies in soft electronics aim to attain complete measurement of the body, mapping various stimulations like temperature, electrophysiological signals, and mechanical strains. However, conventional approach requires many sensor networks that cover the entire curvilinear surfaces of the target area. We introduce a new measuring system, a novel electronic skin integrated with a deep neural network that captures dynamic motions from a distance without creating a sensor network. The device detects minute deformations from the unique laser-induced crack structures. A single skin sensor decodes the complex motion of five finger motions in real-time, and the rapid situation learning (RSL) ensures stable operation regardless of its position on the wrist. The sensor is also capable of extracting gait motions from pelvis. This technology is expected to provide a turning point in health-monitoring, motion tracking, and soft robotics.
Twist-tailoring Coulomb correlations in van der Waals homobilayers
Authors: Merkl Philipp , Mooshammer Fabian , Brem Samuel , Girnghuber Anna , Lin Kai-Qiang , Weigl Leonard , Liebich Marlene , Yong Chaw-Keong , Gillen Roland , Maultzsch Janina , Lupton John M. , Malic Ermin , Huber Rupert
Published: May 2020

The recent discovery of artificial phase transitions induced by stacking monolayer materials at magic twist angles represents a paradigm shift for solid state physics. Twist-induced changes of the single-particle band structure have been studied extensively, yet a precise understanding of the underlying Coulomb correlations has remained challenging. Here we reveal in experiment and theory, how the twist angle alone affects the Coulomb-induced internal structure and mutual interactions of excitons. In homobilayers of WSe2, we trace the internal 1s–2p resonance of excitons with phase-locked mid-infrared pulses as a function of the twist angle. Remarkably, the exciton binding energy is renormalized by up to a factor of two, their lifetime exhibits an enhancement by more than an order of magnitude, and the exciton-exciton interaction is widely tunable. Our work opens the possibility of tailoring quasiparticles in search of unexplored phases of matter in a broad range of van der Waals heterostructures.
A modular biomimetic strategy for the synthesis of macrolide P-glycoprotein inhibitors via Rh-catalyzed C-H activation
Authors: Chen Lu , Quan Haitian , Xu Zhongliang , Wang Hao , Xia Yuanzhi , Lou Liguang , Yang Weibo
Published: May 2020

One of the key challenges to overcome multidrug resistance (MDR) in cancer is the development of more effective and general strategies to discover bioactive scaffolds. Inspired by natural products, we describe a strategy to achieve this goal by modular biomimetic synthesis of scaffolds of (Z)-allylic-supported macrolides. Herein, an Rh(III)-catalyzed native carboxylic acid-directed and solvent-free C−H activation allylation with high stereoselectivity and chemoselectivity is achieved. The generated poly-substituted allylic alcohol as a multifunctional and biomimetic building block is crucial for the synthesis of (Z)-allylic-supported macrolides. Moreover, the unique allylic-supported macrolides significantly potentiate the sensitivity of tumor cells to cytotoxic agents such as vinorelbine and doxetaxel by reversing p170-glycoprotein-mediated MDR. Our findings will inspire the evolution of synthetic chemistry and open avenues for expedient and diversified synthesis of bioactive macrocyclic molecules.
Author Correction: Automatic diagnosis of the 12-lead ECG using a deep neural network
Authors: Ribeiro Antônio H. , Ribeiro Manoel Horta , Paixão Gabriela M. M. , Oliveira Derick M. , Gomes Paulo R. , Canazart Jéssica A. , Ferreira Milton P. S. , Andersson Carl R. , Macfarlane Peter W. , Meira Wagner , Schön Thomas B. , Ribeiro Antonio Luiz P.
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The clinical course of schizophrenia in women and men—a nation-wide cohort study
Authors: Sommer Iris E. , Tiihonen Jari , van Mourik Anouk , Tanskanen Antti , Taipale Heidi
Published: May 2020

Gender differences in schizophrenia have been reported in different aspect of the course of disease and may urge special clinical interventions for female patients. Current literature provides insufficient information to design guidelines for treating women with schizophrenia. We aim to quantify the clinical course of schizophrenia in men and women on premorbid hospitalizations and prescription drugs, age at diagnosis, pharmacological treatment, comorbidity, number of re-hospitalizations, and mortality. Our nationwide cohort study included all patients admitted for the first time to hospital during 2000–2014 for schizophrenia or schizo-affective disorder in Finland. Gender differences were compared with logistic regression, by calculating incidence rates, and mortality was assessed with Cox proportional hazard model. We included 7142 women and 9006 men with schizophrenia/schizo-affective disorder and found that both women (71%) and men (70%) had often been hospitalized for another psychiatric disorder in the 5 years before diagnosis. In women, the last psychiatric hospitalization before schizophrenia/schizo-affective diagnosis was often for mood disorders (62%, OR 2.56, 95% CI 2.28–2.87). Men were diagnosed earlier (mean 34.4 [SD12.6] vs. 38.2 [SD 13.8]) with peak incidence around 22, while incidence in women declining only slowly between age 18 and 65. During ten years follow-up, 69.5% of both genders needed at least one re-hospitalization, with slightly more hospitalizations in women. Women were less often prescribed clozapine or long-acting antipsychotics. Mortality was lower in women (HR = 0.54, 95% CI 0.50–0.60), with fewer suicide and cardiovascular deaths, but more cancer deaths. These results suggest a diagnostic delay for women, which might be shortened by screening women aged 20–65 participating in affective disorder programs. As number of hospitalizations is not lower for women, clinicians should take care not to undertreat women with schizophrenia.
Brain-transportable soy dipeptide, Tyr-Pro, attenuates amyloid β peptide25-35-induced memory impairment in mice
Authors: Tanaka Mitsuru , Kiyohara Hayato , Yoshino Atsuko , Nakano Akihiro , Takata Fuyuko , Dohgu Shinya , Kataoka Yasufumi , Matsui Toshiro
Published: May 2020

In this study, experiments on amyloid β peptide25-35-induced mice were performed to provide in vivo evidence on the potential of the blood–brain barrier transportable soy dipeptide, Tyr-Pro, in combating memory impairment. We demonstrated for the first time that oral administration of Tyr-Pro (100 mg/kg, twice a day) in mice for 16 days significantly improved impaired memory by spontaneous alternation and shortened step-through latency in amyloid β-induced mice.