bluuebunny/crossref_metadata_2025 huggingface dataset:
“Laws of Fear” in the EU: The Precautionary Principle and Public Health Restrictions to Free Movement of Persons in the Time of COVID-19
Authors: GOLDNER LANG Iris
Published: February 2021

COVID-19 has demonstrated the fragility of EU free movement rules when we are faced with an unknown virus of such magnitude and strength that it threatens our lives, health systems, economies and society. The aim of this text is to show the dynamics between the threat of COVID-19 and the rules imposed as a response to the pandemic, which have impacted the functioning of the EU internal market and the Schengen area. The text will concentrate on the application of the precautionary principle and public health restrictions, caused by COVID-19, to free movement of persons in the EU. The analysis will lead to three conclusions. First, it will be shown that the decisions to apply free movement restrictions and the logic followed in the EU COVID-19-related documents can be viewed as a triumph of the precautionary principle. Second, it will be argued that implementing the precautionary principle has a transformative effect on the application of the principle of proportionality in EU law. Finally, it will be shown that COVID-19 has emphasised and increased the difference between the conditions for the applicability of public health restrictions when compared to restrictions based on public policy and public security grounds.
GILLES DELEUZE AND BERNARDO BERTOLUCCI ON PLATO'S CAVE
Authors: Giannopoulou Zina
Published: February 2021

The allegory of the Cave in Republic 514a–18d is one of the most memorable Platonic images. The depiction of chained humans in a cavernous dwelling looking at shadows of objects cast on a parapet in front of them but unable to locate the objects themselves until one of them is freed, turns around to see the objects, and finally leaves the cave has haunted and inspired readers throughout the centuries. The prisoners are said to be ‘like us’ (515a), which is taken to refer either to human life in general or to human life in corrupt political environments. Plato's core metaphysical and epistemological doctrines are thought to inhere in the Cave, his belief that the sensible world, represented by the cave, holds people captive to defective and erroneous appearances, and that only philosophy can free and enlighten them, leading them out of the cave to the intelligible realm of the eternal Forms. The cave then houses captives since childhood who believe that shadows of artifacts exhaust reality, and captors who project images of artifacts on the wall and thereby manipulate what the captives see and hear.
THE WASPS DANCE, THE WASPS SING
Authors: duBois Page
Published: February 2021

Looking at us from all sides, you'll find that in our character and lifestyle we're in all respects most like wasps. First, no creature is more sharp-tempered than we are when irritated, or more cantankerous. Then again, we engineer everything else just like wasps: we gather in swarms as if into nests, some of us judging in the archon's court, some before the Eleven, and some in the Odeum, packed in tight against the walls like this, hunched toward the ground and hardly moving, like grubs in their cells. We're very resourceful in making a living, too: we sting everybody and so provide our daily bread.
Implications of neural networks for how we think about brain function
Authors: Robinson David A.
Published: February 2021

Engineers use neural networks to control systems too complex for conventional engineering solutions. To examine the behavior of individual hidden units would defeat the purpose of this approach because it would be largely uninterpretable. Yet neurophysiologists spend their careers doing just that! Hidden units contain bits and scraps of signals that yield only arcane hints about network function and no information about how its individual units process signals. Most literature on single-unit recordings attests to this grim fact. On the other hand, knowing a system's function and describing it with elegant mathematics tell one very little about what to expect of interneuronal behavior. Examples of simple networks based on neurophysiology are taken from the oculomotor literature to suggest how single-unit interpretability might decrease with increasing task complexity. It is argued that trying to explain how any real neural network works on a cell-by-cell, reductionist basis is futile and we may have to be content with trying to understand the brain at higher levels of organization.
CHARACTERIZATION OF THE TAIL BEHAVIOR OF A CLASS OF BEKK PROCESSES: A STOCHASTIC RECURRENCE EQUATION APPROACH
Authors: Matsui Muneya , Pedersen Rasmus Søndergaard
Published: February 2021

We consider conditions for strict stationarity and ergodicity of a class of multivariate BEKK processes

$(X_t : t=1,2,\ldots )$
and study the tail behavior of the associated stationary distributions. Specifically, we consider a class of BEKK-ARCH processes where the innovations are assumed to be Gaussian and a finite number of lagged

$X_t$
’s may load into the conditional covariance matrix of

$X_t$
. By exploiting that the processes have multivariate stochastic recurrence equation representations, we show the existence of strictly stationary solutions under mild conditions, where only a fractional moment of

$X_t$
may be finite. Moreover, we show that each component of the BEKK processes is regularly varying with some tail index. In general, the tail index differs along the components, which contrasts with most of the existing literature on the tail behavior of multivariate GARCH processes. Lastly, in an empirical illustration of our theoretical results, we quantify the model-implied tail index of the daily returns on two cryptocurrencies.
Modelling, computation and analysis on combustion of explosives
Authors: SAID S. , SMITH F. T. , CURTIS J. P.
Published: February 2021

When an explosive burns, gaseous products are formed as a result. The interaction of the burning solid and gas is not well understood. More specifically, the process of the gaseous product heating the explosive is yet to be explored in detail. The present work sets out to fill some of that gap using mathematical modelling: this aims to track the temperature profile in the explosive. The work begins by modelling single-step reactions using a simple Arrhenius model. The model is then extended to include three-step reaction. An alternative asymptotic approach is also employed. There is close agreement between results from the full reaction-diffusion problem and the asymptotic problem.
Clinically diagnosed iron and iodine deficiencies and disorders in the entire population of US military service members from 1997 to 2015
Authors: Knapik Joseph J , Farina Emily K , Fulgoni Victor L , Lieberman Harris R
Published: February 2021

Objective:

Iron and/or iodine deficiencies can have multiple serious adverse health outcomes, but examination of incidence rates of these deficiencies has rarely been conducted in any large population. This study examined incidence rates, temporal trends and demographic factors associated with medically diagnosed iron and iodine deficiencies/disorders in US military service members (SM).

Design:

The Defense Medical Epidemiological Database (DMED) was queried for medical visits of active duty SM to obtain specific International Classification of Diseases, Version 9, codes involving clinically diagnosed iron and iodine deficiencies/disorders.

Setting:

Analysis of existing database (DMED).

Participants:

Entire population of US military SM from 1997 to 2015 (average n per year = 1 382 266, 15 % women).

Results:

Overall incidence rates for iron and iodine were 104 and 36 cases/100 000 person-years, respectively. Over the 19-year period, rates for iron disorders increased steadily (108 % for men, 177 % for women). Rates for iodine disorders also increased steadily for men (91 %), but, for women, there was an initial rise followed by a later decline. Overall, women’s rates were 12 and 10 times higher than men’s for iron and iodine, respectively. Compared with whites, blacks and those of other races had higher rates of deficiencies of both minerals. Incidence rates for iodine deficiency increased substantially with age.

Conclusions:

The overall incidence of clinically diagnosed iron and iodine deficiency among SM was low, but increased over the 19 years examined, and certain demographic groups were at significantly greater risk. Given the unexpected increases in incidence of these mineral disorders, increased surveillance may be appropriate.

Clinical Trial Registration No. ISRCTN58987177 (http//:www.isrctn.com/ISRCTN58987177)
Age difference in the combined effect of soda drinks consumption and body adiposity on hyperuricaemia in US adults
Authors: Lin Wei-Ting , Kao Yu-Hsiang , Lin Hui-Yi , Li Mirandy S , Luo Ting , Fritz Jackson M , Seal David W , Lee Chien-Hung , Hu Chih-Yang , Tseng Tung-Sung
Published: February 2021

Objective:

To evaluate age-related differences in the independent/combined association of added sugar intake from soda and body adiposity with hyperuricaemia in gender-stratified US adults.

Design:

Consumption of added sugar from soda was calculated from 24-h dietary interviews and categorised into none, regular and excessive consumption. Hyperuricaemia was defined as serum uric acid levels >417 mmol/l in men and >357 mmol/l in women. Multiple regression models with interaction terms and logistic models adjusted for covariates were conducted under survey-data modules.

Setting:

National Health and Nutrition Examination Survey during 2007–2016.

Participants:

15 338 adults without gout, failing kidneys, an estimated glomerular filtration rate < 30 or diabetes were selected.

Results:

The age-stratified prevalence rate of hyperuricaemia was 18·8–20·4 % in males and 6·8–17·3 % in females. Hyperuricaemia prevalence of approximately 50 % was observed in young and middle age males who consumed excessive added sugar from soda. Excessive added sugar intake was observed to be associated with 1·5- to 2·0-fold and 2·0- to 2·3-fold increased risk of the probability of hyperuricaemia in young and middle age males and middle age females, respectively. Study participants, regardless of age or gender, who were obese and consumed excessive added sugar from soda had the highest risk of having hyperuricaemia.

Conclusions:

Our study revealed that the association between hyperuricaemia and consumption of excessive added sugar from soda may vary by age and gender. Obese adults who consumed excessive added sugar from soda had the highest risk of hyperuricaemia, a finding that was found across all age-specific groups for both genders.
Mesiodens in Scanning Electron Microscope
Authors: Jędrych B , Matysiak W , Rumiński M , Czerny K , Kawka B
Published: February 2021

Extended abstract of a paper presented at MC 2007, 33rd DGE Conference
in Saarbrücken, Germany, September 2 – September 7, 2007
Growth-correlated structural and chemical properties of ZnTe
nanowires
Authors: Kirmse H , Neumann W , Kret S , Dłużewski P , Janik E , Karczewski G , Wojtowicz T
Published: February 2021

Extended abstract of a paper presented at MC 2007, 33rd DGE Conference
in Saarbrücken, Germany, September 2 – September 7, 2007
Adult Attachment, Conflict Resolution Style and Relationship Quality among Spanish Young-adult Couples
Authors: González-Ortega Eva , Orgaz Begoña , Vicario-Molina Isabel , Fuertes Antonio
Published: February 2021

The evidence of the interrelationships between adult attachment, conflict resolution style and relationship quality in couple relationships shows some inconsistencies and it is mostly based on English-speaking adult samples, as well as on individuals’ rather than on both couple members’ reports. Therefore, the aim was to examine the associations between adult attachment, conflict resolution style and relationship quality from a dyadic approach. A sample of 405 heterosexual young couples completed online the brief version of the Experiences in Close Relationships-Revised Questionnaire, the respondent version of the Conflict Resolution Styles Inventory, and a 4-item measure of relationship quality. Avoidance attachment showed a stronger negative correlation than anxiety with relationship quality. Withdrawal and conflict engagement styles were more highly correlated with avoidance and anxiety, respectively. At a dyadic level, relationship quality was negatively predicted by actor avoidance attachment and positively predicted by partner relationship quality. No actor or partner effects of conflict resolution style on relationship quality were observed. Overall, partners with higher attachment anxiety and avoidance reported more dysfunctional conflict resolution styles and less satisfaction with the relationship.
A Qualitative Study Exploring Well-Being and the Potential Impact of	Work-Related Stress Among Commercial Airline Pilots
Authors: Cullen Paul , Cahill Joan , Gaynor Keith
Published: February 2021

Abstract. Increasing evidence suggests that commercial airline pilots can experience physical, mental, and social health difficulties. Qualitative interviews with commercial airline pilots explored the relationship between work-related stress and well-being. Participatory workshops involving pilots were conducted. The methodology of this action-based research involved a blend of person-centered design approaches; specifically, “stakeholder evaluation” and “participatory design.” The findings further support the hypothesis that pilot well-being is being negatively affected by the nature of their work. The biopsychosocial model of the lived experience of a pilot, as presented in this paper, provides a useful structure to examine pilot well-being, and to identify and scope potential coping strategies to self-manage health and well-being issues associated with the job of being a pilot.
Investigating Treatment Adherence of British and Greek Patients With	Type 2 Diabetes Mellitus
Authors: Menti Despoina , Limbert Caroline , Lyrakos Georgios
Published: February 2021

Abstract. Background: Treatment adherence is associated with a number of personal characteristics (e.g., self-esteem, self-efficacy, locus of control) and illness perceptions. However, there is a lack of studies for Type 2 Diabetes Mellitus (T2DM). Aims: The aim of this study was to compare adherence behavior of British and Greek people with T2DM and examine the association between personal characteristics, illness perceptions, and adherence. Method: This was a cross-cultural, cross-sectional study. Five hundred eighty participants completed questionnaires, 208 males (35.9%) and 372 females (64.1%) with a mean age of 49 years. Regression analyses and t-tests were used. Results: Personal characteristics and illness perceptions predicted adherence and British patients reported better exercise adherence while Greek patients reported better diet and medication adherence; both groups reported suboptimal adherence. Self-efficacy, Health Locus of Control (HLoC), and illness perceptions were the main adherence determinants. Limitations: The use of self-reports and the convenience sampling method are the main limitations of this study. Conclusion: The findings address a significant gap in research and can inform future adherence-enhancing interventions to promote the well-being of people with T2DM.
Force‐Balance Analysis of Stress Changes During the Subduction‐Collision Transition and Implications for the Rise of Mountain Belts
Authors: Dielforder A. , Hampel A.
Published: February 2021

Mountain height at convergent plate margins is limited by the megathrust shear force, but it remains unclear how this constraint affects the topographic evolution and mountain building at the transition from subduction to collision. Generally, mountain height increases during the subduction‐collision transition in response to crustal thickening or processes like mantle delamination and slab breakoff, but the main parameters controlling how much mountain height increases remain poorly understood. Here we show, based on analytical and finite‐element force‐balance models, that the increase in mountain height depends on the magnitude of the megathrust shear force and the reduction of submarine margin relief. During the subduction stage, the shear force is balanced by the gravitational effect of the margin relief and the deviatoric stresses in the upper plate are low. When the submarine margin relief is reduced during the closure of the ocean basin, the effect of the gravitational force decreases and the upper plate experiences enhanced deviatoric compression, which allows the mountain height to increase until a near‐neutral stress state beneath the high mountains is restored. If the increase in mountain height cannot keep pace with the submarine relief reduction, the compression of the upper plate increases by a few tens of MPa, which promotes tectonic shortening and mountain building. Our analysis implies that mountain height can increase by hundreds of meters to a few kilometers during collision, depending primarily on the trench depth during the subduction stage and possible syncollisional changes of the megathrust shear force.
Reservoir Computing as a Tool for Climate Predictability Studies
Authors: Nadiga Balasubramanya T.
Published: February 2021

Reduced‐order dynamical models play a central role in developing our understanding of predictability of climate irrespective of whether we are dealing with the actual climate system or surrogate climate models. In this context, the linear inverse modeling (LIM) approach, by capturing a few essential interactions between dynamical components of the full system, has proven valuable in providing insights into predictability of the full system. We demonstrate that reservoir computing (RC), a form of learning suitable for systems with chaotic dynamics, provides an alternative nonlinear approach that improves on the predictive skill of the LIM approach. We do this in the example setting of predicting sea surface temperature in the North Atlantic in the preindustrial control simulation of a popular earth system model, the Community Earth System Model so that we can compare the performance of the new RC‐based approach with the traditional LIM approach both when learning data are plentiful and when such data are more limited. The improved predictive skill of the RC approach over a wide range of conditions—larger number of retained EOF coefficients, extending well into the limited data regime, etc.—suggests that this machine‐learning technique may have a use in climate predictability studies. While the possibility of developing a climate emulator—the ability to continue the evolution of the system on the attractor long after failing to be able to track the reference trajectory—is demonstrated in the Lorenz‐63 system, it is suggested that further development of the RC approach may permit such uses of the new approach in more realistic predictability studies.
Deep Heat: Proxies, Miocene Ice, and an End in Sight for Paleoclimate Paradoxes?
Authors: Evans David
Published: February 2021

The mid Miocene represents an important target for paleoclimatic study because the atmospheric CO2 concentration ranged from near modern values to ∼800 ppm, while a large, dynamic Antarctic ice sheet was likely to have been present throughout much of this interval. In this special issue, Modestou et al. (2020) (doi.org/10.1029/2020PA003927) reconstruct deep ocean warmth based on the clumped isotopic composition of benthic foraminifera, a technique that allows the ice volume and thermal components of the benthic oxygen isotope stack to be separated. These data reveal a very warm deep ocean while simultaneously suggesting that continental ice volume may, at times, have been greater than today. Here, I review these results in the context of recent developments in geochemical proxies and ice sheet modeling, and explore how the presence of a large Miocene ice sheet could be reconciled with CO2 at least as high as present. More broadly, I argue that many of the 'paradoxes' that pepper the paleoclimate literature result as much from our imperfect understanding of the proxies, as from our understanding of the climate system. Robust proxies with a well‐understood mechanistic basis, as employed by Modestou et al. (2020), as well as advances in model‐data comparability usher in a new era of palaeoclimate research; an exciting future of untangling Earth's myriad past climate states awaits.
Nonlinearity and Multivariate Dependencies in the Terrestrial Leg of Land‐Atmosphere Coupling
Authors: Hsu Hsin , Dirmeyer Paul A.
Published: February 2021

Most studies of land‐atmosphere coupling have focused on bivariate linear statistics like correlation. However, more complex dependencies exist, including nonlinear relationships between components of land‐atmosphere coupling and the transmutability of relationships between soil moisture and surface heat fluxes under different environmental conditions. In this study, a technique called multivariate mutual information, based on information theory, is proposed to quantify how surface heat fluxes depend on both surface energy and wetness conditions, that is, net radiation and soil moisture, seasonally across the globe using reanalysis data. Such interdependency is then decomposed into linear and nonlinear contributions, which are further decomposed as different components explainable as the unique contribution from individual surface conditions, redundant contributions shared by both surface conditions, and the synergistic contribution from the concurrent action of net radiation and soil moisture. In reanalysis data, the dependency linearly contributed from soil moisture bears a similar global pattern to previously identified hot spots of coupling. The linear unique contributions of net radiation and soil moisture are mainly nonoverlapping, which suggests two separate regimes are governed by either energy or water limitations. These patterns persist when the nonlinearity is superimposed, thus reinforcing the validity of the land‐atmospheric coupling hot spot paradigm and the spatial division of energy‐limited as well as water‐limited regions. Nevertheless, strong nonlinear relationships are detected, particularly over subtropical regions. Synergistic components are found across the globe, implying widespread multidimensional physical relationships among net radiation, soil moisture, and surface heat fluxes that previously had only been inferred locally.
FACEts of mechanical regulation in the morphogenesis of craniofacial structures
Authors: Du Wei , Bhojwani Arshia , Hu Jimmy K.
Published: February 2021

During embryonic development, organs undergo distinct and programmed morphological changes as they develop into their functional forms. While genetics and biochemical signals are well recognized regulators of morphogenesis, mechanical forces and the physical properties of tissues are now emerging as integral parts of this process as well. These physical factors drive coordinated cell movements and reorganizations, shape and size changes, proliferation and differentiation, as well as gene expression changes, and ultimately sculpt any developing structure by guiding correct cellular architectures and compositions. In this review we focus on several craniofacial structures, including the tooth, the mandible, the palate, and the cranium. We discuss the spatiotemporal regulation of different mechanical cues at both the cellular and tissue scales during craniofacial development and examine how tissue mechanics control various aspects of cell biology and signaling to shape a developing craniofacial organ.
Cryo-EM structural analysis of FADD:Caspase-8 complexes defines the catalytic dimer architecture for co-ordinated control of cell fate
Authors: Fox Joanna L. , Hughes Michelle A. , Meng Xin , Sarnowska Nikola A. , Powley Ian R. , Jukes-Jones Rebekah , Dinsdale David , Ragan Timothy J. , Fairall Louise , Schwabe John W. R. , Morone Nobuhiro , Cain Kelvin , MacFarlane Marion
Published: February 2021

Regulated cell death is essential in development and cellular homeostasis. Multi-protein platforms, including the Death-Inducing Signaling Complex (DISC), co-ordinate cell fate via a core FADD:Caspase-8 complex and its regulatory partners, such as the cell death inhibitor c-FLIP. Here, using electron microscopy, we visualize full-length procaspase-8 in complex with FADD. Our structural analysis now reveals how the FADD-nucleated tandem death effector domain (tDED) helical filament is required to orientate the procaspase-8 catalytic domains, enabling their activation via anti-parallel dimerization. Strikingly, recruitment of c-FLIPS into this complex inhibits Caspase-8 activity by altering tDED triple helix architecture, resulting in steric hindrance of the canonical tDED Type I binding site. This prevents both Caspase-8 catalytic domain assembly and tDED helical filament elongation. Our findings reveal how the plasticity, composition and architecture of the core FADD:Caspase-8 complex critically defines life/death decisions not only via the DISC, but across multiple key signaling platforms including TNF complex II, the ripoptosome, and RIPK1/RIPK3 necrosome.
Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology
Authors: Chen Vincent L. , Du Xiaomeng , Chen Yanhua , Kuppa Annapurna , Handelman Samuel K. , Vohnoutka Rishel B. , Peyser Patricia A. , Palmer Nicholette D. , Bielak Lawrence F. , Halligan Brian , Speliotes Elizabeth K.
Published: February 2021

Serum liver enzyme concentrations are the most frequently-used laboratory markers of liver disease, a major cause of mortality. We conduct a meta-analysis of genome-wide association studies of liver enzymes from UK BioBank and BioBank Japan. We identified 160 previously-unreported independent alanine aminotransferase, 190 aspartate aminotransferase, and 199 alkaline phosphatase genome-wide significant associations, with some affecting multiple different enzymes. Associated variants implicate genes that demonstrate diverse liver cell type expression and promote a range of metabolic and liver diseases. These findings provide insight into the pathophysiology of liver and other metabolic diseases that are associated with serum liver enzyme concentrations.
Structure and binding properties of Pangolin-CoV spike glycoprotein inform the evolution of SARS-CoV-2
Authors: Wrobel Antoni G. , Benton Donald J. , Xu Pengqi , Calder Lesley J. , Borg Annabel , Roustan Chloë , Martin Stephen R. , Rosenthal Peter B. , Skehel John J. , Gamblin Steven J.
Published: February 2021

Coronaviruses of bats and pangolins have been implicated in the origin and evolution of the pandemic SARS-CoV-2. We show that spikes from Guangdong Pangolin-CoVs, closely related to SARS-CoV-2, bind strongly to human and pangolin ACE2 receptors. We also report the cryo-EM structure of a Pangolin-CoV spike protein and show it adopts a fully-closed conformation and that, aside from the Receptor-Binding Domain, it resembles the spike of a bat coronavirus RaTG13 more than that of SARS-CoV-2.
Photodegradation of carbon dots cause cytotoxicity
Authors: Liu Yue-Yue , Yu Nan-Yang , Fang Wen-Di , Tan Qiao-Guo , Ji Rong , Yang Liu-Yan , Wei Si , Zhang Xiao-Wei , Miao Ai-Jun
Published: February 2021

Carbon dots (CDs) are photoluminescent nanomaterials with wide-ranging applications. Despite their photoactivity, it remains unknown whether CDs degrade under illumination and whether such photodegradation poses any cytotoxic effects. Here, we show laboratory-synthesized CDs irradiated with light degrade into molecules that are toxic to both normal (HEK-293) and cancerous (HeLa and HepG2) human cells. Eight days of irradiation photolyzes 28.6-59.8% of the CDs to <3 kilo Dalton molecules, 1431 of which are detected by high-throughput, non-target high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Molecular network and community analysis further reveal 499 cytotoxicity-related molecules, 212 of which contain polyethylene glycol, glucose, or benzene-related structures. Photo-induced production of hydroxyl and alkyl radicals play important roles in CD degradation as affected by temperature, pH, light intensity and wavelength. Commercial CDs show similar photodegraded products and cytotoxicity profiles, demonstrating that photodegradation-induced cytotoxicity is likely common to CDs regardless of their chemical composition. Our results highlight the importance of light in cytocompatibility studies of CDs.
Ligand-directed two-step labeling to quantify neuronal glutamate receptor trafficking
Authors: Ojima Kento , Shiraiwa Kazuki , Soga Kyohei , Doura Tomohiro , Takato Mikiko , Komatsu Kazuhiro , Yuzaki Michisuke , Hamachi Itaru , Kiyonaka Shigeki
Published: February 2021

The regulation of glutamate receptor localization is critical for development and synaptic plasticity in the central nervous system. Conventional biochemical and molecular biological approaches have been widely used to analyze glutamate receptor trafficking, especially for α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate-type glutamate receptors (AMPARs). However, conflicting findings have been reported because of a lack of useful tools for analyzing endogenous AMPARs. Here, we develop a method for the rapid and selective labeling of AMPARs with chemical probes, by combining affinity-based protein labeling and bioorthogonal click chemistry under physiological temperature in culture medium. This method allows us to quantify AMPAR distribution and trafficking, which reveals some unique features of AMPARs, such as a long lifetime and a rapid recycling in neurons. This method is also successfully expanded to selectively label N-methyl-D-aspartate-type glutamate receptors. Thus, bioorthogonal two-step labeling may be a versatile tool for investigating the physiological and pathophysiological roles of glutamate receptors in neurons.
Sprouty2 limits intestinal tuft and goblet cell numbers through GSK3β-mediated restriction of epithelial IL-33
Authors: Schumacher Michael A. , Hsieh Jonathan J. , Liu Cambrian Y. , Appel Keren L. , Waddell Amanda , Almohazey Dana , Katada Kay , Bernard Jessica K. , Bucar Edie B. , Gadeock Safina , Maselli Kathryn M. , Washington M. Kay , Grikscheit Tracy C. , Warburton David , Rosen Michael J. , Frey Mark R.
Published: February 2021

Dynamic regulation of intestinal cell differentiation is crucial for both homeostasis and the response to injury or inflammation. Sprouty2, an intracellular signaling regulator, controls pathways including PI3K and MAPKs that are implicated in differentiation and are dysregulated in inflammatory bowel disease. Here, we ask whether Sprouty2 controls secretory cell differentiation and the response to colitis. We report that colonic epithelial Sprouty2 deletion leads to expanded tuft and goblet cell populations. Sprouty2 loss induces PI3K/Akt signaling, leading to GSK3β inhibition and epithelial interleukin (IL)-33 expression. In vivo, this results in increased stromal IL-13+ cells. IL-13 in turn induces tuft and goblet cell expansion in vitro and in vivo. Sprouty2 is downregulated by acute inflammation; this appears to be a protective response, as VillinCre;Sprouty2F/F mice are resistant to DSS colitis. In contrast, Sprouty2 is elevated in chronic colitis and in colons of inflammatory bowel disease patients, suggesting that this protective epithelial-stromal signaling mechanism is lost in disease.
Biofilms harbour Clostridioides difficile, serving as a reservoir for recurrent infection
Authors: Normington Charmaine , Moura Ines B. , Bryant Jessica A. , Ewin Duncan J. , Clark Emma V. , Kettle Morgan J. , Harris Hannah C. , Spittal William , Davis Georgina , Henn Matthew R. , Ford Christopher B. , Wilcox Mark H. , Buckley Anthony M.
Published: February 2021

C. difficile infection (CDI) is a worldwide healthcare problem with ~30% of cases failing primary therapy, placing a burden on healthcare systems and increasing patient morbidity. We have little understanding of why these therapies fail. Here, we use a clinically validated in vitro gut model to assess the contribution of biofilms towards recurrent disease and to investigate biofilm microbiota-C. difficile interactions. Initial experiments show that C. difficile cells became associated with the colonic biofilm microbiota and are not depleted by vancomycin or faecal microbiota transplant therapies. We observe that transferring biofilm encased C. difficile cells into a C. difficile naïve but CDI susceptible model induces CDI. Members of the biofilm community can impact C. difficile biofilm formation by acting either antagonistically or synergistically. We highlight the importance of biofilms as a reservoir for C. difficile, which can be a cause for recurrent infections.
The role of brain perivascular space burden in early-stage Parkinson’s disease
Authors: Shen Ting , Yue Yumei , Zhao Shuai , Xie Juanjuan , Chen Yanxing , Tian Jun , Lv Wen , Lo Chun-Yi Zac , Hsu Yi-Cheng , Kober Tobias , Zhang Baorong , Lai Hsin-Yi
Published: February 2021

Perivascular space (PVS) is associated with neurodegenerative diseases, while its effect on Parkinson’s disease (PD) remains unclear. We aimed to investigate the clinical and neuroimaging significance of PVS in basal ganglia (BG) and midbrain in early-stage PD. We recruited 40 early-stage PD patients and 41 healthy controls (HCs). Both PVS number and volume were calculated to evaluate PVS burden on 7 T magnetic resonance imaging images. We compared PVS burden between PD and HC, and conducted partial correlation analysis between PVS burden and clinical and imaging features. PD patients had a significantly more serious PVS burden in BG and midbrain, and the PVS number in BG was significantly correlated to the PD disease severity and L-dopa equivalent dosage. The fractional anisotropy and mean diffusivity values of certain subcortical nuclei and white matter fibers within or nearby the BG and midbrain were significantly correlated with the ipsilateral PVS burden indexes. Regarding to the midbrain, the difference between bilateral PVS burden was, respectively, correlated to the difference between fiber counts of white fiber tract passing through bilateral substantia nigra in PD. Our study suggests that PVS burden indexes in BG are candidate biomarkers to evaluate PD motor symptom severity and aid in predicting medication dosage. And our findings also highlight the potential correlations between PVS burden and both grey and white matter microstructures.
Secure quantum key distribution with a subset of malicious devices
Authors: Zapatero Víctor , Curty Marcos
Published: February 2021

The malicious manipulation of quantum key distribution (QKD) hardware is a serious threat to its security, as, typically, neither end users nor QKD manufacturers can validate the integrity of every component of their QKD system in practice. One possible approach to re-establish the security of QKD is to use a redundant number of devices. Following this idea, we address various corruption models of the possibly malicious devices and show that, compared to the most conservative model of active and collaborative corrupted devices, natural assumptions allow to significantly enhance the secret key rate or considerably reduce the necessary resources. Furthermore, we show that, for most practical situations, the resulting finite-size secret key rate is similar to that of the standard scenario assuming trusted devices.
Experimental evidence for Zeeman spin–orbit coupling in layered antiferromagnetic conductors
Authors: Ramazashvili R. , Grigoriev P. D. , Helm T. , Kollmannsberger F. , Kunz M. , Biberacher W. , Kampert E. , Fujiwara H. , Erb A. , Wosnitza J. , Gross R. , Kartsovnik M. V.
Published: February 2021

Most of solid-state spin physics arising from spin–orbit coupling, from fundamental phenomena to industrial applications, relies on symmetry-protected degeneracies. So does the Zeeman spin–orbit coupling, expected to manifest itself in a wide range of antiferromagnetic conductors. Yet, experimental proof of this phenomenon has been lacking. Here we demonstrate that the Néel state of the layered organic superconductor κ-(BETS)2FeBr4 shows no spin modulation of the Shubnikov–de Haas oscillations, contrary to its paramagnetic state. This is unambiguous evidence for the spin degeneracy of Landau levels, a direct manifestation of the Zeeman spin–orbit coupling. Likewise, we show that spin modulation is absent in electron-doped Nd1.85Ce0.15CuO4, which evidences the presence of Néel order in this cuprate superconductor even at optimal doping. Obtained on two very different materials, our results demonstrate the generic character of the Zeeman spin–orbit coupling.
Accelerometer data collected with a minimum set of wearable sensors from subjects with Parkinson’s disease
Authors: Daneault Jean-Francois , Vergara-Diaz Gloria , Parisi Federico , Admati Chen , Alfonso Christina , Bertoli Matilde , Bonizzoni Edoardo , Carvalho Gabriela Ferreira , Costante Gianluca , Fabara Eric Eduardo , Fixler Naama , Golabchi Fatemah Noushin , Growdon John , Sapienza Stefano , Snyder Phil , Shpigelman Shahar , Sudarsky Lewis , Daeschler Margaret , Bataille Lauren , Sieberts Solveig K. , Omberg Larsson , Moore Steven , Bonato Paolo
Published: February 2021

Parkinson’s disease (PD) is a neurodegenerative disorder associated with motor and non-motor symptoms. Current treatments primarily focus on managing motor symptom severity such as tremor, bradykinesia, and rigidity. However, as the disease progresses, treatment side-effects can emerge such as on/off periods and dyskinesia. The objective of the Levodopa Response Study was to identify whether wearable sensor data can be used to objectively quantify symptom severity in individuals with PD exhibiting motor fluctuations. Thirty-one subjects with PD were recruited from 2 sites to participate in a 4-day study. Data was collected using 2 wrist-worn accelerometers and a waist-worn smartphone. During Days 1 and 4, a portion of the data was collected in the laboratory while subjects performed a battery of motor tasks as clinicians rated symptom severity. The remaining of the recordings were performed in the home and community settings. To our knowledge, this is the first dataset collected using wearable accelerometers with specific focus on individuals with PD experiencing motor fluctuations that is made available via an open data repository.
Electronic healthcare records and external outcome data for hospitalized patients with heart failure
Authors: Zhang Zhongheng , Cao Linghong , Chen Rangui , Zhao Yan , Lv Lukai , Xu Ziyin , Xu Ping
Published: February 2021

Heart failure is one of the most important reasons for hospitalization among elderly individuals and is associated with significant mortality and morbidity. Epidemiological studies require the establishment of high-quality databases. Several datasets that primarily involve heart failure populations have been established in Western countries and have generated many high-quality studies. However, no such dataset is available from China. Due to differences in genetic background and healthcare systems between China and Western countries, the establishment of a heart failure database for the Chinese population is urgently needed. We performed a retrospective single-center observational study to collect data regarding the characteristics of heart failure patients in China by integrating electronic healthcare records and follow-up outcome data. The study collected information for a total of 2,008 patients with heart failure, containing 166 attributes.
Nonmechanical parfocal and autofocus features based on wave propagation distribution in lensfree holographic microscopy
Authors: Dharmawan Agus Budi , Mariana Shinta , Scholz Gregor , Hörmann Philipp , Schulze Torben , Triyana Kuwat , Garcés-Schröder Mayra , Rustenbeck Ingo , Hiller Karsten , Wasisto Hutomo Suryo , Waag Andreas
Published: February 2021

Performing long-term cell observations is a non-trivial task for conventional optical microscopy, since it is usually not compatible with environments of an incubator and its temperature and humidity requirements. Lensless holographic microscopy, being entirely based on semiconductor chips without lenses and without any moving parts, has proven to be a very interesting alternative to conventional microscopy. Here, we report on the integration of a computational parfocal feature, which operates based on wave propagation distribution analysis, to perform a fast autofocusing process. This unique non-mechanical focusing approach was implemented to keep the imaged object staying in-focus during continuous long-term and real-time recordings. A light-emitting diode (LED) combined with pinhole setup was used to realize a point light source, leading to a resolution down to 2.76 μm. Our approach delivers not only in-focus sharp images of dynamic cells, but also three-dimensional (3D) information on their (x, y, z)-positions. System reliability tests were conducted inside a sealed incubator to monitor cultures of three different biological living cells (i.e., MIN6, neuroblastoma (SH-SY5Y), and Prorocentrum minimum). Altogether, this autofocusing framework enables new opportunities for highly integrated microscopic imaging and dynamic tracking of moving objects in harsh environments with large sample areas.
Honey bee hives decrease wild bee abundance, species richness, and fruit count on farms regardless of wildflower strips
Authors: Angelella G. M. , McCullough C. T. , O’Rourke M. E.
Published: February 2021

Pollinator refuges such as wildflower strips are planted on farms with the goals of mitigating wild pollinator declines and promoting crop pollination services. It is unclear, however, whether or how these goals are impacted by managed honey bee (Apis melliferaL.) hives on farms. We examined how wildflower strips and honey bee hives and/or their interaction influence wild bee communities and the fruit count of two pollinator-dependent crops across 21 farms in the Mid-Atlantic U.S. Although wild bee species richness increased with bloom density within wildflower strips, populations did not differ significantly between farms with and without them whereas fruit counts in both crops increased on farms with wildflower strips during one of 2 years. By contrast, wild bee abundance decreased by 48%, species richness by 20%, and strawberry fruit count by 18% across all farm with honey bee hives regardless of wildflower strip presence, and winter squash fruit count was consistently lower on farms with wildflower strips with hives as well. This work demonstrates that honey bee hives could detrimentally affect fruit count and wild bee populations on farms, and that benefits conferred by wildflower strips might not offset these negative impacts. Keeping honey bee hives on farms with wildflower strips could reduce conservation and pollination services.
Zebrafish tracking using YOLOv2 and Kalman filter
Authors: Barreiros Marta de Oliveira , Dantas Diego de Oliveira , Silva Luís Claudio de Oliveira , Ribeiro Sidarta , Barros Allan Kardec
Published: February 2021

Fish show rapid movements in various behavioral activities or associated with the presence of food. However, in periods of rapid movement, the rate at which occlusion occurs among the fish is quite high, causing inconsistency in the detection and tracking of fish, hindering the fish's identity and behavioral trajectory over a long period of time. Although some algorithms have been proposed to solve these problems, most of their applications were made in groups of fish that swim in shallow water and calm behavior, with few sudden movements. To solve these problems, a convolutional network of object recognition, YOLOv2, was used to delimit the region of the fish heads to optimize individual fish detection. In the tracking phase, the Kalman filter was used to estimate the best state of the fish's head position in each frame and, subsequently, the trajectories of each fish were connected among the frames. The results of the algorithm show adequate performances in the trajectories of groups of zebrafish that exhibited rapid movements.
The variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival
Authors: Houtsma Danny , de Groot Stefanie , Baak-Pablo Renee , Kranenbarg Elma Meershoek -Klein , Seynaeve Caroline M. , van de Velde Cornelis J. H. , Böhringer Stefan , Kroep Judith R. , Guchelaar Henk -Jan , Gelderblom Hans
Published: February 2021

The PvuII (rs2234693) Single Nucleotide Polymorphism (SNP) in the gene coding for the estrogen receptor-1 (ESR1), has been found associated with outcome in tamoxifen treated patients with early hormone-receptor positive breast cancer. However, it remains unclear whether this SNP is a predictive marker for tamoxifen efficacy or a prognostic marker for breast cancer outcome. The aim of this study was to examine the prognostic potential of this SNP in postmenopausal early breast cancer patients treated with adjuvant exemestane. Dutch postmenopausal patients randomised to 5 years of adjuvant exemestane of whom tissue was available (N = 807) were selected from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial database. The SNP rs2234693 in the ESR1 gene was genotyped on DNA from formalin-fixed paraffin embedded (FFPE) tumor tissue using Taqman assays and related to the primary endpoint disease-free survival (DFS) and secondary endpoint overall survival (OS). Survival analyses were performed using Cox regression analysis. In total 805 patients were included in the analyses (median follow up of 5.22 years) and genotypes were obtained in 97% of the samples. The variant T allele of PvuII in ESR1 (rs2234693) was associated with a better DFS (hazard ratio (HR) 0.689, 95% confidence interval (CI) 0.480–0.989, P = 0.044) in univariate analysis only, and a better OS in both univariate (HR 0.616, 95%, CI 0.411–0.923, P = 0.019) and multivariate analyses (HR 0.571, 95% CI 0.380–0.856, P = 0.007), consistent with a prognostic rather than a predictive drug response effect. Variation of PvuII in the ESR1 gene is related to OS in postmenopausal, early HR + breast cancer patients treated with exemestane in the TEAM study. Variation in the ESR1 gene may therefore be a prognostic marker of early breast cancer survival, and warrants further research.
Impaired inhibition of return during free-viewing behaviour in patients with schizophrenia
Authors: Okada Ken-ichi , Miura Kenichiro , Fujimoto Michiko , Morita Kentaro , Yoshida Masatoshi , Yamamori Hidenaga , Yasuda Yuka , Iwase Masao , Inagaki Mikio , Shinozaki Takashi , Fujita Ichiro , Hashimoto Ryota
Published: February 2021

Schizophrenia affects various aspects of cognitive and behavioural functioning. Eye movement abnormalities are commonly observed in patients with schizophrenia (SZs). Here we examined whether such abnormalities reflect an anomaly in inhibition of return (IOR), the mechanism that inhibits orienting to previously fixated or attended locations. We analyzed spatiotemporal patterns of eye movement during free-viewing of visual images including natural scenes, geometrical patterns, and pseudorandom noise in SZs and healthy control participants (HCs). SZs made saccades to previously fixated locations more frequently than HCs. The time lapse from the preceding saccade was longer for return saccades than for forward saccades in both SZs and HCs, but the difference was smaller in SZs. SZs explored a smaller area than HCs. Generalized linear mixed-effect model analysis indicated that the frequent return saccades served to confine SZs’ visual exploration to localized regions. The higher probability of return saccades in SZs was related to cognitive decline after disease onset but not to the dose of prescribed antipsychotics. We conclude that SZs exhibited attenuated IOR under free-viewing conditions, which led to restricted scene scanning. IOR attenuation will be a useful clue for detecting impairment in attention/orienting control and accompanying cognitive decline in schizophrenia.