bluuebunny/crossref_metadata_2025 huggingface dataset:
Landelijke ambities versus lokale uitwerking: gemeentelijk gezondheidsbeleid en lokale tabaksontmoediging laten te wensen over
Authors: Bruijn L. Michelle , Hessels Judith A.
Published: June 2022

Samenvatting

In Nederland is roken nog steeds de belangrijkste oorzaak van ziekte en sterfte. Een Rookvrije Generatie creëren is daarom een belangrijke landelijke doelstelling van de overheid. De ambitie is dat in 2040 geen enkel kind rookt of ooit zal gaan roken. De gemeenten en de rijksoverheid spelen beide een belangrijke rol bij de bescherming van de volksgezondheid. De preventiecyclus, waarbij gemeenten een lokaal gezondheidsbeleid dienen op te stellen naar aanleiding van het landelijke gezondheidsbeleid, kenmerkt de gedeelde bevoegdheid om zorg te dragen voor de aanpak van gezondheidsproblemen, zoals roken. Deze bijdrage brengt de huidige stand van zaken omtrent het lokale gezondheids- en tabaksontmoedigingsbeleid in kaart voor de gemeenten in de provincies Groningen, Utrecht en Zeeland (N = 49). Het onderzoek toont aan dat vrijwel alle onderzochte gemeenten (96%) niet aan de wettelijke vereisten van de preventiecyclus voldoen en dat lokaal tabaksontmoedigingsbeleid achterblijft in vergelijking met de landelijke doelen en verwachtingen. Het onderzoek laat daarnaast zien dat de lokale verschillen groot zijn. De nationale overheid zal met gemeenten moeten samenwerken om de landelijke gezondheidsdoelen, zoals tabaksontmoediging, een centrale en structurele plek te geven op de lokale agenda.
Copyright Compensation in the Finnish Sanctioning System – A Remedy for Ungained Benefit or an Unjustified Punishment?
Authors: Tammenlehto Laura
Published: June 2022

Copyright compensation is a special civil remedy for copyright infringements and the unlawful use of copyright according to Finnish copyright legislation. Its purpose is to ensure compensation to the rightholder in situations where the infringement is evident, but proving the harm or loss is difficult. Copyright compensation aims to prevent the unlawful and infringing use of copyrighted material. This article studies which purposes may be pursued with copyright compensation and which criteria must be fulfilled in this pursuit. The article focuses on studying the level of prevention, which may be pursued with a remedy without it becoming a punishment. The article points out that case law has started to emphasize the preventive function of copyright compensation. Due to this, the remedy (i.e. copyright compensation) has taken on punitive elements, which, according to the Finnish legal system, are prohibited to be given as civil remedies. This jeopardizes foreseeability of the use of law and the protection of the defendant’s legitimate rights. The article suggests that the protection of the legitimate rights of the defendant should be better ensured in imposing copyright compensation, and that strong prevention should be pursued with other measures.
A model-based design of an onboard stereo vision system: obstacle motion estimation for cooperative automated vehicles
Authors: Kemsaram Narsimlu , Das Anweshan , Dubbelman Gijs
Published: June 2022

Cooperative automated vehicle software needs to use advanced software engineering design methodologies to manage the complexity of distributed software. This article presents a design model of a stereo vision system for cooperative automated vehicles based on object-oriented analysis and design methodologies and unified modeling language concepts. We use a rational unified process and the 4+1 architectural view model to design the stereo vision system. The designed model is a part of the perception system of the ego vehicle. The stereo vision system continuously perceives the traffic environment using an on-board front-facing stereo camera and sends information to the vehicle control system. The stereo vision system is developed on Ubuntu 16.04 LTS platform with the Nvidia DriveWorks framework using the C++ programming language, and it is deployed on Nvidia Drive PX2 automotive-grade embedded hardware platform. The designed and developed system is evaluated on the Carla simulation environment and the Renault Twizy cooperative automated vehicle research platform. The experimental results show that the approach is applicable, and the system is capable of running in real-time.
Fantasies of the Bookstore
Authors: Muse Eben J.
Published: June 2022

This Element surveys the place of the bookstore in the creative imagination (the fantasies of the bookstore) through a study of novels in which bookstores play a prominent role in the setting or plot. Nearly 500 'bookstore novels' published since the first in 1917 have been identified. The study borrows the concept of 'meaningful locations' from the field of human geography to assess fictional bookstores as narrative events rather than static backgrounds. As a meaningful location, the bookstore creates the potential for events that can occur both within the place of the store and in the wider space within which it functions. Elements of the narrative space include its spatio-temporal location, its locale or composition, and the events which these elements generate to define the bookstore's sense of place.
Pronominal deficiency: A view from Malagasy
Authors: Paul Ileana , Travis Lisa deMena
Published: June 2022

Various proposals have been made in the literature, arguing that bound pronouns are, in some sense, deficient. This article tests this hypothesis with Malagasy pronouns, specifically in the context of Zribi-Hertz and Mbolatianavalona's (1999) claim that Malagasy pronouns may be bound only when they are missing the NumP layer of DP. Zribi-Hertz and Mbolatianavalona show further that other syntactic properties are also attached to the lack of NumP. The variety of Malagasy investigated here (Malagasy2), behaves differently from the one described by Zribi-Hertz and Mbolatianavalona (Malagasy1), and these differences lead to two conclusions. First, there are no syntactically deficient pronouns in Malagasy2, yet these syntactically complete pronouns may, in fact, be bound. Second, Zribi-Hertz and Mbolatianavalona are nevertheless correct that the lack of NumP accounts for a cluster of properties, since none of these distinctions between pronouns that they describe are found in Malagasy2. More broadly, we conclude that pronominal binding does not require syntactic deficiency.
The impact of COVID-19 on disease epidemiology, family dynamics, and social justice in Minnesota: All that you cannot see
Authors: Schleiss Mark R. , Blazar Bruce , Chapman Emily P. , Cutler Gretchen J. , Cutts Diana B. , Eder Milton Mickey , Li Shengxu , Mason Susan M. , Bretscher Brianna M. , Neglia Joseph P. , Scal Peter B. , Winter Stuart S.
Published: June 2022

Objective:

The COVID-19 pandemic presented a challenge to established seed grant funding mechanisms aimed at fostering collaboration in child health research between investigators at the University of Minnesota (UMN) and Children’s Hospitals and Clinics of Minnesota (Children’s MN). We created a “rapid response,” small grant program to catalyze collaborations in child health COVID-19 research. In this paper, we describe the projects funded by this mechanism and metrics of their success.

Methods:

Using seed funds from the UMN Clinical and Translational Science Institute, the UMN Medical School Department of Pediatrics, and the Children’s Minnesota Research Institute, a rapid response request for applications (RFAs) was issued based on the stipulations that the proposal had to: 1) consist of a clear, synergistic partnership between co-PIs from the academic and community settings; and 2) that the proposal addressed an area of knowledge deficit relevant to child health engendered by the COVID-19 pandemic.

Results:

Grant applications submitted in response to this RFA segregated into three categories: family fragility and disruption exacerbated by COVID-19; knowledge gaps about COVID-19 disease in children; and optimizing pediatric care in the setting of COVID-19 pandemic restrictions. A series of virtual workshops presented research results to the pediatric community. Several manuscripts and extramural funding awards underscored the success of the program.

Conclusions:

A “rapid response” seed funding mechanism enabled nascent academic-community research partnerships during the COVID-19 pandemic. In the context of the rapidly evolving landscape of COVID-19, flexible seed grant programs can be useful in addressing unmet needs in pediatric health.
The Effect of an Earthquake Experienced During Pregnancy on Maternal Health and Birth Outcomes
Authors: Amarpoor Mesrkanlou Hossein , Ghaemmaghami Hezaveh Seyed Jamal , Tahmasebi Sanaz , Nikniaz Zeinab , Nikniaz Leila
Published: June 2022

Objective:

Maternal health in pregnancy and birth outcomes were compared between pre- and post-Varzaghan earthquake.

Methods:

In this retrospective descriptive study, before and after the earthquake, 550 and 450 women were enrolled respectively. Neonatal weight, height, and head circumference, as well as maternal weight gain and hemoglobin (Hb) levels were obtained using medical records at health centers. Chi-square test and Independent t-test were used to analyze differences in pregnancy outcomes. A P-value less than 0.05 was considered significant.

Results:

A significant increase in inadequate gestational weight gain (44.1% vs 58.9%) was observed (P = 0.043) before and after the earthquake. The mean hemoglobin level in the first trimester before the earthquake was significantly higher than after the earthquake (P = 0.001). Before–after earthquake comparisons showed that the mean birth weight, birth height, and birth head circumference were decreased significantly (P < 0.05). In addition, the rates of preterm birth (18.91% vs 10.90%), abortion (17.11% vs 10.54%), and stillbirth (3.78% vs 1.82%) were increased significantly after the earthquake (P < 0.05).

Conclusions:

Earthquake causes inadequate gestational weight gain and decreased hemoglobin levels, which lead to adverse birth outcomes. More longitudinal and well-designed studies are desired to investigate the longitudinal consequences of disasters on susceptible groups.
Foreign to whom? Constraining the moral foreign language effect on bilinguals’ language experience
Authors: Del Maschio Nicola , Del Mauro Gianpaolo , Bellini Camilla , Abutalebi Jubin , Sulpizio Simone
Published: June 2022

The moral foreign language effect (MFLE) describes how people’s decisions may change when a moral dilemma is presented in either their native (NL) or foreign language (FL). Growing attention is being directed to unpacking what aspects of bilingualism may influence the MFLE, though with mixed or inconclusive results. The current study aims to bridge this gap by adopting a conceptualization of bilingualism that frames this construct as a composite and continuous measure. In a between-group analysis, we asked 196 Italian–English bilinguals to perform a moral dilemmas task in either their NL (i.e., Italian) or FL (i.e., English). In a within-group analysis, we evaluated the effects of FL age of acquisition, FL proficiency, and language dominance – all measured as continuous variables – on moral decision-making. Overall, findings indicate that differences within bilinguals’ language experience impact moral decisions in an FL. However, the effect of the linguistic factors considered was not ubiquitous across dilemmas, and not always emerged into a MFLE. In light of these results, our study addresses the importance of treating bilingualism as multidimensional, rather than a unitary variable. It also discusses the need to reconceptualize the FLE and its implications on moral decision-making.
The natural occurring RRR-α-Tocopherol and synthetic α-Tocopherol stereoisomers in maternal plasma, cord plasma and breast milk among six regions of China
Authors: Lou Zeru , Dang Guodong , Wu Shiyin , Wu Ke , Cai Meiqin
Published: June 2022

The study aimed to investigate RRR-α-Tocopherol and synthetic α-Tocopherol stereoisomers in maternal plasma, cord plasma and breast milk from different regions of China, providing a reference for further guidance on maternal diet and the potential need to supplement mothers with vitamin E. Two hundred and twenty-one sample sets from maternal plasma, cord plasma and three stages of milk (colostrum: 1–5 d after delivery; transitional milk: 10–15 d; mature milk: 40–45 d) were collected longitudinally in six regions of Shanghai, Guangzhou, Tianjin, Chengdu, Lanzhou and Changchun. α-Tocopherol and the stereoisomers were determined by HPLC with a fluorescence detector. The RRR configuration accounted for more than 80 % of α-Tocopherol in maternal plasma, cord plasma and breast milk. Overall, there were regional differences both in α-Tocopherol and RRR. There were significant correlations between α-Tocopherol and RRR in maternal plasma, cord plasma and milk (P < 0.001). As well as negative correlations among α-Tocopherol, RRR and weight-related indicators, which refer to pre-gestation weight and BMI, pre-delivery weight and BMI and pregnancy weight gain, in almost all of samples. This study suggested that RRR-α-Tocopherol was the dominant configuration of α-Tocopherol and the main active form of vitamin E in the early life, guiding the rational supplement of pregnant women and the addition of α-Tocopherol in infant formula milk powder.
Parents tune their vowels to the emergence of children’s words
Authors: ODIJK Lotte , GILLIS Steven
Published: June 2022

The aim of this study was to investigate the acoustic vowel space area in infant directed speech (IDS). The research question is whether the vowel space is expanded or remains constant in IDS. A corpus of spontaneous interactions of 9 dyads followed monthly from the age of 6 to 24 months was analyzed. The occurrences in the parents’ speech of each word that the children eventually acquired were extracted. The surface of the vowel triangle and the convex hull of all vowels were computed. The main result is that the development of the vowel space in IDS follows an inverted U-shaped curve: the vowel space starts relatively small, gradually increases as the child’s first word use approaches, and decreases again afterwards. These findings show that parents adapt their articulation to the evolving linguistic abilities of their child, and this adaptation can be detected at the level of individual lexical items.
A Storm, An Explosion, and Flying Rocks - An Unusual Injury due to a Lightning Strike in the Mountains
Authors: Kosiński Sylweriusz , Aleksandrowicz Dawid , Serafinowicz Zofia
Published: June 2022

Background:

Most injuries observed in victims of lightning strikes can be explained by electrothermal phenomena. Blast penetrating injuries caused by a lightning-strike-induced explosion of a nearby structure are rarely reported.

Case Presentation:

Here reported is the case of a patient with numerous mixed injuries caused by a lightning strike, including deep lacerations of both hips and thighs with rock fragments embedded in the wounds. Surgical removal of rock fragments from deep areas of the right hip and right lower leg was necessary. The cause of the formation of rock missiles was the lightning-strike-induced explosion of rock. Rapid evaporation of water enclosed in rock crevices was presumably the main force underlying the explosion.

Conclusion:

Blast penetrating injuries should be considered and excluded in all patients struck by lightning, particularly when occurring in rocky terrain. The diagnosis and treatment of such injuries can be difficult and require special preparation.
Is spiritual well-being related to survival time of inpatients with advanced cancer? An East Asian cohort study
Authors: Hiratsuka Yusuke , Suh Sang-Yeon , Won Seon Hye , Choi Sung Eun , Kim Sun-Hyun , Cheng Shao-Yi , Chen Ping-Jen , Yoon Seok-Joon , Koh Su-Jin , Park Shin Ae , Seo Ji-Yeon , Hui David , Yamaguchi Takashi , Morita Tatsuya , Tsuneto Satoru , Mori Masanori , Inoue Akira
Published: June 2022

Objectives

It has been suggested that psychosocial factors are related to survival time of inpatients with cancer. However, there are not many studies examining the relationship between spiritual well-being (SWB) and survival time among countries. This study investigated the relationship between SWB and survival time among three East Asian countries.

Methods

This international multicenter cohort study is a secondary analysis involving newly admitted inpatients with advanced cancer in palliative care units in Japan, South Korea, and Taiwan. SWB was measured using the Integrated Palliative Outcome Scale (IPOS) at admission. We performed multivariate analysis using the Cox proportional hazards model to identify independent prognostic factors.

Results

A total of 2,638 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. The median survival time was 18.0 days (95% confidence interval [CI] 16.5–19.5) in Japan, 23.0 days (95% CI 19.9–26.1) in Korea, and 15.0 days (95% CI 13.0–17.0) in Taiwan. SWB was a significant factor correlated with survival in Taiwan (hazard ratio [HR] 1.27; 95% CI 1.01–1.59; p = 0.04), while it was insignificant in Japan (HR 1.10; 95% CI 1.00–1.22; p = 0.06), and Korea (HR 1.02; 95% CI 0.77–1.35; p = 0.89).

Significance of results

SWB on admission was associated with survival in patients with advanced cancer in Taiwan but not Japan or Korea. The findings suggest the possibility of a positive relationship between spiritual care and survival time in patients with far advanced cancer.
Building a virtual Roman city: teaching history through video game design
Authors: Forsyth Harrison
Published: June 2022

In October of 2018, a pedagogical experiment was conducted at York University, Toronto, Canada, in which students were given an assignment. For this assignment they were to conduct research on a variety of Roman public buildings in groups, build digital reconstructions of them using the Unity 3D game engine, and present them to the class in the form of a virtual reality (VR) simulation. In doing so, students were able to create a virtual built environment based on their research, navigate it, and discuss the space with a sense of immersion and scale. Using this experiment as a case study, the goal of this article is twofold: firstly, to assess the pedagogical efficacy of constructionist approaches to teaching students about Roman architecture, specifically using VR and video game design technology. The second goal is to address the technical and pedagogical challenges of using game design software in the classroom and to propose ways in which this assignment can be improved in the future.
Prefrontal Neuronal Activities During Active Retrieval of Information	From Long-Term Memory
Authors: Andreau Jorge Mario , Funahashi Shintaro
Published: June 2022

Abstract. Single-neuron studies performed in the primate prefrontal cortex (PFC) revealed that retaining information in working memory (WM) is associated with sustained firing during the delay period in a match-to-sample task. On the other hand, single-neuron studies using a pair-association task have shown that retrieving information from long-term memory (LTM) is related to two kinds of neural activities: decreasing activity representing information linked to the sample stimulus and increasing activity predicting information for the forthcoming matching stimulus. To further examine neuronal behavioral patterns during LTM retrieval, we used a partial correlation coefficient analysis to analyze single-neuron activities in the PFC while monkeys performed the visual pair-association task. Results showed that, for most of the task-related neurons, firing activity depicted information from the sample stimulus. Nevertheless, some neurons showed an opposite pattern, this is, increasing activity during the delay period, possibly indicating a prospective memory coding from LTM. Interestingly, both activities seem to be present at different degrees as the delay period progresses. Together, these results unveil a new aspect of PFC neurons when retrieving unseen information from LTM.
Detection of Forced Change Within Combined Climate Fields Using Explainable Neural Networks
Authors: Rader Jamin K. , Barnes Elizabeth A. , Ebert‐Uphoff Imme , Anderson Chuck
Published: June 2022

Assessing forced climate change requires the extraction of the forced signal from the background of climate noise. Traditionally, tools for extracting forced climate change signals have focused on one atmospheric variable at a time, however, using multiple variables can reduce noise and allow for easier detection of the forced response. Following previous work, we train artificial neural networks to predict the year of single‐ and multi‐variable maps from forced climate model simulations. To perform this task, the neural networks learn patterns that allow them to discriminate between maps from different years—that is, the neural networks learn the patterns of the forced signal amidst the shroud of internal variability and climate model disagreement. When presented with combined input fields (multiple seasons, variables, or both), the neural networks are able to detect the signal of forced change earlier than when given single fields alone by utilizing complex, nonlinear relationships between multiple variables and seasons. We use layer‐wise relevance propagation, a neural network explainability tool, to identify the multivariate patterns learned by the neural networks that serve as reliable indicators of the forced response. These “indicator patterns” vary in time and between climate models, providing a template for investigating inter‐model differences in the time evolution of the forced response. This work demonstrates how neural networks and their explainability tools can be harnessed to identify patterns of the forced signal within combined fields.
Multiple Types of Porosity – P‐Wave Velocity Relationships for the Nankai Trough
Authors: Yabe S. , Hamada Y. , Kitamura M. , Fukuchi R. , Hashimoto Y.
Published: June 2022

The empirical relationship between the porosity and P‐wave velocity is a useful tool for probing large‐scale underground physical properties and stress states based on P‐wave velocity structures acquired by seismic surveys. In this study, the porosity‐velocity curves were examined using local core sample and logging datasets acquired along the Kumano transect in the Nankai Trough, Southwest Japan. We tested Hashimoto et al.’s (2010) hypothesis that slope apron and accreted sediments have different relationships. Our advantage is using a large amount of logging and core data obtained at multiple sites in the Nankai Trough under various geological conditions, from the incoming oceanic plate to the inner wedge. We identified multiple types of porosity – P‐wave velocity relationships: 1) The first type agrees with the low‐velocity model in the global empirical relation of Erickson and Jarrard 1998), which is observed at lithostatic stress state condition (incoming upper Shikoku basin and slope sediments), 2) The second type consistent with high‐velocity models of the global empirical relation observed at compressive stress state condition (accreted sediments), which have a higher velocity and larger dependence on the porosity than the first type with the same porosity, and 3) The third type for incoming sediments with high smectite content has lower velocity than the first type. Based on our results, the transition between the first and second porosity – velocity relationships occurs in the prism toe, implying that compressive stress due to subduction controls acoustic properties and the lithification process of these sediments.
A biosensing system employing nanowell microelectrode arrays to record the intracellular potential of a single cardiomyocyte
Authors: Xiang Yuting , Liu Haitao , Yang Wenjian , Xu Zhongyuan , Wu Yue , Tang Zhaojian , Zhu Zhijing , Zeng Zhiyong , Wang Depeng , Wang Tianxing , Hu Ning , Zhang Diming
Published: June 2022

Electrophysiological recording is a widely used method to investigate cardiovascular pathology, pharmacology and developmental biology. Microelectrode arrays record the electrical potential of cells in a minimally invasive and high-throughput way. However, commonly used microelectrode arrays primarily employ planar microelectrodes and cannot work in applications that require a recording of the intracellular action potential of a single cell. In this study, we proposed a novel measuring method that is able to record the intracellular action potential of a single cardiomyocyte by using a nanowell patterned microelectrode array (NWMEA). The NWMEA consists of five nanoscale wells at the center of each circular planar microelectrode. Biphasic pulse electroporation was applied to the NWMEA to penetrate the cardiomyocyte membrane, and the intracellular action potential was continuously recorded. The intracellular potential recording of cardiomyocytes by the NWMEA measured a potential signal with a higher quality (213.76 ± 25.85%), reduced noise root-mean-square (~33%), and higher signal-to-noise ratio (254.36 ± 12.61%) when compared to those of the extracellular recording. Compared to previously reported nanopillar microelectrodes, the NWMEA could ensure single cell electroporation and acquire high-quality action potential of cardiomyocytes with reduced fabrication processes. This NWMEA-based biosensing system is a promising tool to record the intracellular action potential of a single cell to broaden the usage of microelectrode arrays in electrophysiological investigation.
RhoA signaling increases mitophagy and protects cardiomyocytes against ischemia by stabilizing PINK1 protein and recruiting Parkin to mitochondria
Authors: Tu Michelle , Tan Valerie P. , Yu Justin D. , Tripathi Raghav , Bigham Zahna , Barlow Melissa , Smith Jeffrey M. , Brown Joan Heller , Miyamoto Shigeki
Published: June 2022

Mitophagy, a mitochondria-specific form of autophagy, removes dysfunctional mitochondria and is hence an essential process contributing to mitochondrial quality control. PTEN-induced kinase 1 (PINK1) and the E3 ubiquitin ligase Parkin are critical molecules involved in stress-induced mitophagy, but the intracellular signaling mechanisms by which this pathway is regulated are unclear. We tested the hypothesis that signaling through RhoA, a small GTPase, induces mitophagy via modulation of the PINK1/Parkin pathway as a protective mechanism against ischemic stress. We demonstrate that expression of constitutively active RhoA as well as sphingosine-1-phosphate induced activation of endogenous RhoA in cardiomyocytes result in an accumulation of PINK1 at mitochondria. This is accompanied by translocation of Parkin to mitochondria and ubiquitination of mitochondrial proteins leading to recognition of mitochondria by autophagosomes and their lysosomal degradation. Expression of RhoA in cardiomyocytes confers protection against ischemia, and this cardioprotection is attenuated by siRNA-mediated PINK1 knockdown. In vivo myocardial infarction elicits increases in mitochondrial PINK1, Parkin, and ubiquitinated mitochondrial proteins. AAV9-mediated RhoA expression potentiates these responses and a concurrent decrease in infarct size is observed. Interestingly, induction of mitochondrial PINK1 accumulation in response to RhoA signaling is neither mediated through its transcriptional upregulation nor dependent on depolarization of the mitochondrial membrane, the canonical mechanism for PINK1 accumulation. Instead, our results reveal that RhoA signaling inhibits PINK1 cleavage, thereby stabilizing PINK1 protein at mitochondria. We further show that active RhoA localizes at mitochondria and interacts with PINK1, and that the mitochondrial localization of RhoA is regulated by its downstream effector protein kinase D. These findings demonstrate that RhoA activation engages a unique mechanism to regulate PINK1 accumulation, induce mitophagy and protect against ischemic stress, and implicates regulation of RhoA signaling as a potential strategy to enhance mitophagy and confer protection under stress conditions.
β2-adrenergic receptor promotes liver regeneration partially through crosstalk with c-met
Authors: Tao Xiang , Chen Can , Chen Yingxiang , Zhang Luoying , Hu Jiong , Yu Hongjun , Liang Minglu , Fu Qin , Huang Kai
Published: June 2022

The β2-adrenergic receptor (β2AR) is a G protein-coupled receptor (GPCR) that mediates the majority of cellular responses to external stimuli. Aberrant expression of β2AR results in various pathophysiological disorders, including tumorigenesis, but little is known about its role in liver regeneration. This study aims to investigate the impact and the underlying mechanism of β2AR in liver regeneration. Here, we found that β2AR was upregulated during liver regeneration induced by 70% PH. Deletion of β2AR in mice resulted in 62% mortality 2 days post-PH, decreased proliferative marker expression and impaired liver function throughout regeneration. Moreover, AAV8-mediated overexpression of β2AR in hepatocytes accelerated the regeneration process and increased target gene expression. Mechanistically, β2AR recruited G-protein-coupled receptor kinase 2 (GRK2) to the membrane and then formed a complex with c-met to transactivate c-met signaling, which triggered downstream extracellular regulated protein kinase (ERK) signaling activation and nuclear translocation. Inhibition of c-met with SU11274 or ERK with U0126 decreased β2AR overexpression-induced hepatocyte proliferation. Our findings revealed that β2AR might act as a critical mediator regulating liver regeneration by crosstalk with c-met and activation of ERK signaling.
Estimation of the number of inherited prion disease mutation carriers in the UK
Authors: Corbie Rosie , Campbell Tracy , Darwent Lee , Rudge Peter , Collinge John , Mead Simon
Published: June 2022

Inherited prion diseases (IPD) are a set of rare neurodegenerative diseases that are always caused by mutation of the prion protein gene (PRNP). These are highly heterogeneous in clinical presentation and best described by the specific gene mutation, but traditionally include the canonical syndromes familial Creutzfeldt-Jakob disease, Gerstamann-Straussler-Scheinker syndrome, and fatal familial insomnia. In the UK, care of IPD patients and clinical PRNP sequencing have been carried out almost exclusively by the National Prion Clinic and affiliated laboratories since the disease gene was discovered in 1989. Using data obtained over 30 years (1990–2019), this study aimed to provide a greater understanding of the genetic prevalence of IPD using multiple complementary methods. A key source of bias in rare disorders is ascertainment, so we included an analysis based on capture-recapture techniques that may help to minimise ascertainment bias. 225 patients, with 21 different IPD mutations were identified, varying in frequency (with 8/21 mutations comprising over 90% observed cases), derived from 116 kindreds and 151 3-generation families. We estimated a total of 303 UK families (95% CI = 222, 384) segregate IPD mutations, 1091 (95% CI = 720, 1461) UK mutation carriers and a lifetime risk of approximately 1 in 60,000. Simpler methods of measuring prevalence based on extrapolation from the annual incidence of disease, and large scale genomic studies, result in similar estimates of prevalence. These estimates may be of value for planning preventive trials of therapeutics in IPD mutation carriers, prevention of prion disease transmission and provision of specialist services.
Demonstration of a superconducting diode-with-memory, operational at zero magnetic field with switchable nonreciprocity
Authors: Golod Taras , Krasnov Vladimir M.
Published: June 2022

Diode is one of the basic electronic components. It has a nonreciprocal current response, associated with a broken space/time reversal symmetry. Here we demonstrate prototypes of superconducting diodes operational at zero magnetic field. They are based on conventional niobium planar Josephson junctions, in which space/time symmetry is broken by a combination of self-field effect from nonuniform bias and stray fields from a trapped Abrikosov vortex. We demonstrate that nonreciprocity of critical current in such diodes can reach an order of magnitude and rectification efficiency can exceed 70%. Furthermore, we can easily change the diode polarity and switch nonreciprocity on/off by changing the bias configuration and by trapping/removing of a vortex. This facilitates a memory functionality. We argue that such a diode-with-memory can be used for a future generation of in-memory superconducting computers.
Osteocyte CIITA aggravates osteolytic bone lesions in myeloma
Authors: Liu Huan , He Jin , Bagheri-Yarmand Rozita , Li Zongwei , Liu Rui , Wang Zhiming , Bach Duc-hiep , Huang Yung-hsing , Lin Pei , Guise Theresa A. , Gagel Robert F. , Yang Jing
Published: June 2022

Osteolytic destruction is a hallmark of multiple myeloma, resulting from activation of osteoclast-mediated bone resorption and reduction of osteoblast-mediated bone formation. However, the molecular mechanisms underlying the differentiation and activity of osteoclasts and osteoblasts within a myelomatous microenvironment remain unclear. Here, we demonstrate that the osteocyte-expressed major histocompatibility complex class II transactivator (CIITA) contributes to myeloma-induced bone lesions. CIITA upregulates the secretion of osteolytic cytokines from osteocytes through acetylation at histone 3 lysine 14 in the promoter of TNFSF11 (encoding RANKL) and SOST (encoding sclerostin), leading to enhanced osteoclastogenesis and decreased osteoblastogenesis. In turn, myeloma cell–secreted 2-deoxy-D-ribose, the product of thymidine catalyzed by the function of thymidine phosphorylase, upregulates CIITA expression in osteocytes through the STAT1/IRF1 signaling pathway. Our work thus broadens the understanding of myeloma-induced osteolysis and indicates a potential strategy for disrupting tumor-osteocyte interaction to prevent or treat patients with myeloma bone disease.
Warming-induced increase in carbon uptake is linked to earlier spring phenology in temperate and boreal forests
Authors: Gu Hongshuang , Qiao Yuxin , Xi Zhenxiang , Rossi Sergio , Smith Nicholas G. , Liu Jianquan , Chen Lei
Published: June 2022

Under global warming, advances in spring phenology due to rising temperatures have been widely reported. However, the physiological mechanisms underlying the advancement in spring phenology still remain poorly understood. Here, we investigated the effect of temperature during the previous growing season on spring phenology of current year based on the start of season extracted from multiple long-term and large-scale phenological datasets between 1951 and 2018. Our findings indicate that warmer temperatures during previous growing season are linked to earlier spring phenology of current year in temperate and boreal forests. Correspondingly, we observed an earlier spring phenology with the increase in photosynthesis of the previous growing season. These findings suggest that the observed warming-induced earlier spring phenology is driven by increased photosynthetic carbon assimilation in the previous growing season. Therefore, the vital role of warming-induced changes in carbon assimilation should be considered to accurately project spring phenology and carbon cycling in forest ecosystems under future climate warming.
Cellular automaton simulation and experimental validation of eutectic transformation during solidification of Al-Si alloys
Authors: Gu Cheng , Moodispaw Michael P. , Luo Alan A.
Published: June 2022

The morphology of eutectic silicon in solidification microstructure is critical to the performance of Al-Si-based alloys. Simulating eutectic Si phase formation has been a challenge in ICME (integrated computational materials engineering) based design and manufacturing of solidification products of Al-Si-based alloys. In this study, our previous three-dimensional (3-D) cellular automaton (CA) model for α-Al dendritic growth was extended to include eutectic (α-Al + Si) transformation in multi-dendrite domains, providing a complete solidification simulation of critically important Al-Si based alloys. The quantitative results of the Si phase in the eutectic microstructure were experimentally validated using scanning electron microscopy and deep etching techniques. The simulation results show a good agreement with the experimental observations and calculations by the Scheil model and lever rule. This 3-D CA model is useful for predicting and optimizing the solidification microstructure including eutectic transformation during solidification processing such as casting, potentially welding, and additive manufacturing.
Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis
Authors: Abdeen Amr H. , Trist Benjamin G. , Double Kay L.
Published: June 2022

The Bradford Hill model evaluates the causal inference of one variable on another by assessing whether evidence of the suspected causal variable aligns with a set of nine criteria proposed by Bradford Hill, each representing fundamental tenets of a causal relationship. The aim of this study was to use the Bradford Hill model of causation to assess the level of empirical evidence supporting our hypotheses that alterations to iron and copper levels, and iron- and copper-associated proteins and genes, contribute to Parkinson’s disease etiology. We conducted a systematic review of all available articles published to September 2019 in four online databases. 8437 articles matching search criteria were screened for pre-defined inclusion and exclusion criteria. 181 studies met study criteria and were subsequently evaluated for study quality using established quality assessment tools. Studies meeting criteria for moderate to high quality of study design (n = 155) were analyzed according to the Bradford Hill model of causation. Evidence from studies considered of high quality (n = 73) supported a causal role for iron dysregulation in Parkinson’s disease. A causal role for copper dysregulation in Parkinson’s disease was also supported by high quality studies, although substantially fewer studies investigated copper in this disorder (n = 25) compared with iron. The available evidence supports an etiological role for iron and copper dysregulation in Parkinson’s disease, substantiating current clinical trials of therapeutic interventions targeting alterations in brain levels of these metals in Parkinson’s disease.
Error measurements for a quantum annealer using the one-dimensional Ising model with twisted boundaries
Authors: Chancellor Nicholas , Crowley Philip J. D. , Durić Tanja , Vinci Walter , Amin Mohammad H. , Green Andrew G. , Warburton Paul A. , Aeppli Gabriel
Published: June 2022

A finite length ferromagnetic chain with opposite spin polarization imposed at its two ends is one of the simplest frustrated spin models. In the clean classical limit the domain wall inserted on account of the boundary conditions resides with equal probability on any one of the bonds, and the degeneracy is precisely equal to the number of bonds. If quantum mechanics is introduced via a transverse field, the domain wall will behave as a particle in a box, and prefer to be nearer the middle of the chain rather than the ends. A simple characteristic of a real quantum annealer is therefore which of these limits obtains in practice. Here we have used the ferromagnetic chain with antiparallel boundary spins to test a real flux qubit quantum annealer and discover that contrary to both expectations, the domain walls found are non-uniformly distributed on account of effective random longitudinal fields present notwithstanding tuning carried out to zero out such fields when the couplings between qubits are nominally zero. We present a simple derivation of the form of the distribution function for the domain walls, and show also how the effect we have discovered can be used to determine the strength of the effective random fields (noise) characterizing the annealer. The noise measured in this fashion is smaller than what is seen during the single-qubit tuning process, but nonetheless qualitatively affects the outcome of the simulation performed by the annealer.
Clonal structure, stability and dynamics of human memory B cells and circulating plasmablasts
Authors: Phad Ganesh E. , Pinto Dora , Foglierini Mathilde , Akhmedov Murodzhon , Rossi Riccardo L. , Malvicini Emilia , Cassotta Antonino , Fregni Chiara Silacci , Bruno Ludovica , Sallusto Federica , Lanzavecchia Antonio
Published: June 2022

Memory B cells persist for a lifetime and rapidly differentiate into antibody-producing plasmablasts and plasma cells upon antigen re-encounter. The clonal relationship and evolution of memory B cells and circulating plasmablasts is not well understood. Using single-cell sequencing combined with isolation of specific antibodies, we found that in two healthy donors, the memory B cell repertoire was dominated by large IgM, IgA and IgG2 clonal families, whereas IgG1 families, including those specific for recall antigens, were of small size. Analysis of multiyear samples demonstrated stability of memory B cell clonal families and revealed that a large fraction of recently generated plasmablasts was derived from long-term memory B cell families and was found recurrently. Collectively, this study provides a systematic description of the structure, stability and dynamics of the human memory B cell pool and suggests that memory B cells may be active at any time point in the generation of plasmablasts.
Assessment of the frequency of coughing and sneezing triggered by nasopharyngeal swabbing in the pandemic setting
Authors: Cismaru Cosmin Andrei , Chira Sergiu , Cismaru Gabriel Laurentiu , Nutu Andreea Mihaela , Netea Mihai Gheorghe , Berindan-Neagoe Ioana
Published: June 2022

A variety of medical procedures are classified as aerosol generating. However there is no consensus on whether some procedures such as nasopharyngeal swabbing can generate aerosols. During specimen collection, the contact of the nasopharyngeal swab with the respiratory mucosa often triggers defense reflexes such as sneezing and coughing, which generate airborne particles. The accumulation and persistence of a viral load from infectious aerosols for hours after their generation can represent a threat for increased spread of infection. Prospective observational cohort study in individuals tested for RT-PCR SARS-CoV-2 from July to October 2020. Participants were evaluated for the prevalence of aerosol generating events (AGEs) triggered by the nasopharyngeal swabbing. We used descriptive statistics to analyze the data set and the chi-square test for AGE comparison between sexes. Among 1239 individuals, we reported 264 in which AGEs were triggered by the specimen collection. 97 individuals tested positive for SARS-CoV-2, of which 20 presented AGEs. There were no significant differences in the occurrence of AGEs by age, but significant differences have been identified between sex and the occurrence of AGEs both in the SARS-CoV-2 negative and SARS-CoV-2 positive individuals. The prevalence of coughing or sneezing triggered by the nasopharyngeal swabbing was high among tested individuals. Testing facilities should ensure adequate availability of personal protective equipment (PPE) for the testing personnel, ensure appropriate ventilation of the rooms, and develop additional strategies to limit the risk of contamination of other participants to the testing session from potentially infectious and persistent aerosols.
Tyramide-conjugated DNA barcodes enable signal amplification for multiparametric CODEX imaging
Authors: Simonson Paul D. , Valencia Itzel , Patel Sanjay S.
Published: June 2022

Multiparametric imaging allows researchers to measure the expression of many biomarkers simultaneously, allowing detailed characterization of cell microenvironments. One such technique, CODEX, allows fluorescence imaging of >30 proteins in a single tissue section. In the commercial CODEX system, primary antibodies are conjugated to DNA barcodes. This modification can result in antibody dysfunction, and development of a custom antibody panel can be very costly and time consuming as trial and error of modified antibodies proceeds. To address these challenges, we developed novel tyramide-conjugated DNA barcodes that can be used with primary antibodies via peroxidase-conjugated secondary antibodies. This approach results in signal amplification and imaging without the need to conjugate primary antibodies. When combined with commercially available barcode-conjugated primary antibodies, we can very quickly develop working antibody panels. We also present methods to perform antibody staining using a commercially available automated tissue stainer and in situ hybridization imaging on a CODEX platform. Future work will include application of the combined tyramide-based and regular CODEX approach to image specific tumors with their immune cell infiltrates, including biomarkers that are currently difficult to image by regular CODEX.
Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel–Lindau syndrome
Authors: Li Shuijie , Li Wenyu , Yuan Juan , Bullova Petra , Wu Jieyu , Zhang Xuepei , Liu Yong , Plescher Monika , Rodriguez Javier , Bedoya-Reina Oscar C. , Jannig Paulo R. , Valente-Silva Paula , Yu Meng , Henriksson Marie Arsenian , Zubarev Roman A. , Smed-Sörensen Anna , Suzuki Carolyn K. , Ruas Jorge L. , Holmberg Johan , Larsson Catharina , Christofer Juhlin C. , von Kriegsheim Alex , Cao Yihai , Schlisio Susanne
Published: June 2022

Mitochondria are the main consumers of oxygen within the cell. How mitochondria sense oxygen levels remains unknown. Here we show an oxygen-sensitive regulation of TFAM, an activator of mitochondrial transcription and replication, whose alteration is linked to tumours arising in the von Hippel–Lindau syndrome. TFAM is hydroxylated by EGLN3 and subsequently bound by the von Hippel–Lindau tumour-suppressor protein, which stabilizes TFAM by preventing mitochondrial proteolysis. Cells lacking wild-type VHL or in which EGLN3 is inactivated have reduced mitochondrial mass. Tumorigenic VHL variants leading to different clinical manifestations fail to bind hydroxylated TFAM. In contrast, cells harbouring the Chuvash polycythaemia VHLR200W mutation, involved in hypoxia-sensing disorders without tumour development, are capable of binding hydroxylated TFAM. Accordingly, VHL-related tumours, such as pheochromocytoma and renal cell carcinoma cells, display low mitochondrial content, suggesting that impaired mitochondrial biogenesis is linked to VHL tumorigenesis. Finally, inhibiting proteolysis by targeting LONP1 increases mitochondrial content in VHL-deficient cells and sensitizes therapy-resistant tumours to sorafenib treatment. Our results offer pharmacological avenues to sensitize therapy-resistant VHL tumours by focusing on the mitochondria.
Facile synthesis of MnCo2S4 nanosheets as a binder-free electrode material for high performance supercapacitor applications
Authors: Nguyet Ha M. , Tam Le T. T. , Tung Doan T. , Yen Nguyen T. , Dung Hoang T. , Dung Ngo T. , Phan N. Hong , Tuan Le A. , Minh Phan N. , Lu Le T.
Published: June 2022

MnCo2S4 porous nanosheets with excellent electrochemical performance were synthesized by using a simple and effective approach at relatively low temperatures.
Hydrophosphorylation of electron-deficient alkenes and alkynes mediated by convergent paired electrolysis
Authors: Sun Xue , Yang Jianjing , Yan Kelu , Zhuang Xinyu , Yu Jie , Song Xiaodan , Zhang Fanjun , Li Bingwen , Wen Jiangwei
Published: June 2022

A straightforward and practical strategy for hydrophosphorylation of electron-deficient alkenes and alkynes to access γ-ketophosphine oxides, enabled by CPE strategy in the absence of a metal, base, and redox reagent, has been described.
Synergistic influence of FRET, bulk recombination centers, and charge separation in enhancing the visible-light-driven photocatalytic activity of Cu2+-ion-doped ZnO nanoflowers
Authors: Chatterjee Sathi , Kar Asit Kumar
Published: June 2022

Pure ZnO and a group of Cu2+-ion-doped (4, 6, and 8 wt%) ZnO nanomaterials are synthesized using the co-precipitation technique.