bluuebunny/crossref_metadata_2025_split huggingface dataset:
The development and characterization of an E. coli O25B bioconjugate vaccine
Authors: Kowarik Michael , Wetter Michael , Haeuptle Micha A. , Braun Martin , Steffen Michael , Kemmler Stefan , Ravenscroft Neil , De Benedetto Gianluigi , Zuppiger Matthias , Sirena Dominique , Cescutti Paola , Wacker Michael 
Published: March 2021

AbstractExtraintestinal pathogenic Escherichia coli (ExPEC) cause a wide range of clinical diseases such as bacteremia and urinary tract infections. The increase of multidrug resistant ExPEC strains is becoming a major concern for the treatment of these infections and E. coli has been identified as a critical priority pathogen by the WHO. Therefore, the development of vaccines has become increasingly important, with the surface lipopolysaccharide constituting a promising vaccine target. This study presents genetic and structural analysis of clinical urine isolates from Switzerland belonging to the serotype O25. Approximately 75% of these isolates were shown to correspond to the substructure O25B only recently described in an emerging clone of E. coli sequence type 131. To address the high occurrence of O25B in clinical isolates, an O25B glycoconjugate vaccine was prepared using an E. coli glycosylation system. The O antigen cluster was integrated into the genome of E. coli W3110, thereby generating an E. coli strain able to synthesize the O25B polysaccharide on a carrier lipid. The polysaccharide was enzymatically conjugated to specific asparagine side chains of the carrier protein exotoxin A (EPA) of Pseudomonas aeruginosa by the PglB oligosaccharyltransferase from Campylobacter jejuni. Detailed characterization of the O25B-EPA conjugate by use of physicochemical methods including NMR and GC-MS confirmed the O25B polysaccharide structure in the conjugate, opening up the possibility to develop a multivalent E. coli conjugate vaccine containing O25B-EPA.
Ethico-Political Aspects of Conceptualizing Screening: The Case of Dementia
Authors: Gunnarson Martin , Kapeller Alexandra , Zeiler Kristin 
Published: March 2021

AbstractWhile the value of early detection of dementia is largely agreed upon, population-based screening as a means of early detection is controversial. This controversial status means that such screening is not recommended in most national dementia plans. Some current practices, however, resemble screening but are labelled “case-finding” or “detection of cognitive impairment”. Labelled as such, they may avoid the ethical scrutiny that population-based screening may be subject to. This article examines conceptualizations of screening and case-finding. It shows how the definitions and delimitations of the concepts (the what of screening) are drawn into the ethical, political, and practical dimensions that screening assessment criteria or principles are intended to clarify and control (the how of screening, how it is and how it should be performed). As a result, different conceptualizations of screening provide the opportunity to rethink what ethical assessments should take place: the conceptualizations have different ethico-political implications. The article argues that population-based systematic screening, population-based opportunistic screening, and case-finding should be clearly distinguished.
Do policies and institutions matter for pre-tax income inequality? Cross-country evidence
Authors: Vergara Damián 
Published: March 2021

AbstractDo policies and institutions matter for pre-tax income inequality? I build an annual panel of 43 countries for the period 1980–2016 to document cross-country facts. I find robust correlations between pre-tax income shares and economic policy—financial development, trade openness, government expenditure, and income taxation—even after controlling for economic development. I further find that proxies of institutional quality—e.g., state development, corruption, or political exclusion—mediate the relationship between top income shares and economic policy, in particular for trade openness and government expenditure. The role of institutions in allowing or limiting rent-seeking can rationalize the results.
Homeostatic Property Cluster Theory without Homeostatic Mechanisms: Two Recent Attempts and their Costs
Authors: Onishi Yukinori , Serpico Davide 
Published: March 2021

AbstractThe homeostatic property cluster theory (HPC) is widely influential for its ability to account for many natural-kind terms in the life sciences. However, the notion of homeostatic mechanism has never been fully explicated. In 2009, Carl Craver interpreted the notion in the sense articulated in discussions on mechanistic explanation and pointed out that the HPC account equipped with such notion invites interest-relativity. In this paper, we analyze two recent refinements on HPC: one that avoids any reference to the causes of the clustering of properties and one that replaces homeostatic mechanisms with causal networks represented by causal graphs. We argue that the former is too slender to account for some inductive inference in science and the latter, thicker account invites interest-relativity, as the original HPC does. This suggests that human interest will be an un-eliminative part of a satisfactory account of natural kindness. We conclude by discussing the implication of interest-relativity to the naturalness, reality, or objectivity of kinds and indicating an overlooked aspect of natural kinds that requires further studies.
p-Kernel Stein Variational Gradient Descent for Data Assimilation and History Matching
Authors: Stordal Andreas S. , Moraes Rafael J. , Raanes Patrick N. , Evensen Geir 
Published: March 2021

AbstractA Bayesian method of inference known as “Stein variational gradient descent” was recently implemented for data assimilation problems, under the heading of “mapping particle filter”. In this manuscript, the algorithm is applied to another type of geoscientific inversion problems, namely history matching of petroleum reservoirs. In order to combat the curse of dimensionality, the commonly used Gaussian kernel, which defines the solution space, is replaced by a p-kernel. In addition, the ensemble gradient approximation used in the mapping particle filter is rectified, and the data assimilation experiments are re-run with more relevant settings and comparisons. Our experimental results in data assimilation are rather disappointing. However, the results from the subsurface inverse problem show more promise, especially as regards the use of p-kernels.
Categorification of algebraic quantum field theories
Authors: Benini Marco , Perin Marco , Schenkel Alexander , Woike Lukas 
Published: March 2021

AbstractThis paper develops a concept of 2-categorical algebraic quantum field theories (2AQFTs) that assign locally presentable linear categories to spacetimes. It is proven that ordinary AQFTs embed as a coreflective full 2-subcategory into the 2-category of 2AQFTs. Examples of 2AQFTs that do not come from ordinary AQFTs via this embedding are constructed by a local gauging construction for finite groups, which admits a physical interpretation in terms of orbifold theories. A categorification of Fredenhagen’s universal algebra is developed and also computed for simple examples of 2AQFTs.
The social structure of Brexit and the crisis of globalisation
Authors: Dowling Emma 
Published: March 2021

AbstractDespite much protracted debate, there is still no consensus among social scientists as to why a majority of Britons voted to leave the European Union in June 2016. This paper constructs a sociology of Brexit and seeks to interpret the fractious constellations on either side of the Brexit disjuncture. Taking as its point of the departure the resurgence of sociological interest in class in the wake of Brexit and with the rise of right-wing populisms in recent years, the paper argues for a compositional, intersectional and historically dynamic class analysis of Brexit’s political fault-lines within the context of Britain’s neoliberal restructuring. An analytical framework is proposed with which to explain how neoliberal globalisation has transformed British society and its concomitant class relations, accounting for the disarticulation of previous political allegiances. The paper explains the Brexit vote in terms of central social-structural components, including class, ethnicity, geographical region, age, and educational attainment. It is argued that the vote in 2016 to leave the European Union is best interpreted as a residue of a post-war class compromise, while the vote to remain in the European Union reflects a class constellation recomposed by neoliberal globalisation, which is unstable and in crisis. The article concludes with a discussion of the overall implications of the argument presented for a sociological reading of Brexit.
Effect of the Distance from Build Platform and Post-Heat Treatment of AlSi10Mg Alloy Manufactured by Single- and Multi-Laser Selective Laser Melting
Authors: Cerri Emanuela , Ghio Emanuele , Bolelli Giovanni 
Published: March 2021

AbstractIn the present study, AlSi10Mg samples produced by selective laser melting (SLM) were studied. Samples were machined from two types of bars obtained through different methods: either single laser (SL) or multiple laser (ML) machine setup. The bars were built perpendicular to the platform, which was pre-heated at 150 °C (working temperature), up to a height of 300 mm. The effect of the distance from the platform on the mechanical properties was investigated through tensile samples in as-built condition and after unconventional heat treatments (U-HT). Tensile strength changed by 80 MPa along the Z-axis (build direction) for SL case and by 100 MPa for ML case in the as-built samples. Vickers microhardness revealed an analogous gradient. This was correlated to a gradient in intra-granular precipitates' distribution along the Z-axis, as revealed by scanning electron microscopy (SEM). An unconventional heat treatment at 175 °C for 6h slightly improves the mechanical strength; higher temperature treatments at 200 and 225 °C for the same duration cause a progressive decrease in strength with an increase in elongation. The amount and size of the precipitates and the thickness of eutectic Si change with the heat treatment temperature, justifying the mechanical behavior.
Suppression of MD2 inhibits breast cancer in vitro and in vivo
Authors: Zheng S. , Fu W. , Ma R. , Huang Q. , Gu J. , Zhou J. , Lu K. , Guo G. 
Published: March 2021

Abstract
Purpose
To explore the effects of the intervening measure targeting myeloid differentiation 2 (MD2) on breast cancer progression in vitro and in vivo.

Methods
The expression of MD2 in normal breast cells (Hs 578Bst) and three kinds of breast carcinoma cell lines (MCF-7, MDA-MB-231 s and 4T1) were detected by western blot. MTT assay was used to detect the proliferation of 4T1 cells treated by L6H21, cell migration and invasion was measured by wound healing assay and trans-well matrigel invasion assay, respectively. In addition, to further study the role of MD2 in tumor progression, we assessed the effects of inhibition of MD2 on the progression of xenograft tumors in vivo.

Results
The expression of MD2 is much higher in MDA-MB-231 s and 4T1cells than that in normal breast cells (Hs 578Bst) or MCF-7 cells (p < 0.05). In vitro, suppression of MD2 by L6H21 has a significant inhibition of proliferation, migration and invasion in 4T1 cells in dose-dependent manner. In vivo, L6H21 pretreatment significantly improved survival of 4T1-bearing mice (p < 0.05). Additionally, we also observed that none of the mice died from the toxic effect of 10 mg kg−1 L6H21 in 60 days.

Conclusion
Overall, this work indicates that suppression of MD2 shows progression inhibition in vitro and significantly prolong survival in vivo. These findings provide the potential experimental evidence for using MD2 as a therapeutic target of breast carcinoma.
Psychometric evaluation of the mental health continuum – short form in Swedish adolescents
Authors: Söderqvist Fredrik , Larm Peter 
Published: March 2021

AbstractThe Mental Health Continuum – Short form (MHC-SF) is a self-report measure that has been increasingly used to monitor mental well-being at the population level. The aim of this study was to evaluate, for the first time, the psychometric properties of the MHC-SF in a population of Swedish adolescents. First, the evaluation was performed by examining face validity and test–retest reliability obtained in a pre-study. Then using data from the Survey of Adolescent Life in Vestmanland 2020 (n = 3880) we performed confirmatory factor analysis on different factor structures based on theory and previous research. Model-based estimates were calculated for assessing the internal reliability of the factor structure with the best fit. Convergent validity was assessed by bivariate as well as model-based correlations, and test–retest reliability was evaluated by intra-class correlation coefficients. The results show that the MHC-SF is best described with a bifactor model consisting of a dominant general well-being factor and three specific group factors of emotional, social and psychological well-being. Its overall reliability was high to very high, while the reliability of its subscales was low. A practical implication of the latter is that the subcales should not be used on their own because they are more likely to reliably measure the general well-being factor than the specific group factors. Test–retest reliability of the total scale was acceptable, and convergent validity was supported. In conclusion, we consider the Swedish MHC-SF to be a psychometrically sound instrument for monitoring overall mental well-being in Swedish adolescents.
Development and In Vitro Characterization of Transferrin-Decorated Nanoemulsion Utilizing Hydrophobic Ion Pairing for Targeted Cellular Uptake
Authors: Zaichik Sergey , Steinbring Christian , Friedl Julian David , Bernkop-Schnürch Andreas 
Published: March 2021

Abstract
Purpose
The aim of this study was to develop transferrin-conjugated nanoemulsions utilizing hydrophobic ion pairing for a targeted cellular uptake.

Methods
In the lipophilic phase of nanoemulsion composed of 60% oleic acid, 30% Capmul MCM EP and 10% Span 85, 1% cetyltrimethylammonium bromide (CTAB) and 3% phosphatidic acid (PA) were incorporated. After emulsification, the resulting droplets were decorated with human protein transferrin via hydrophobic ion pairing with PA and characterized regarding droplet size and zeta potential. Subsequently, cellular uptake of transferrin-conjugated nanoemulsion was investigated on Caco-2 and HeLa cell lines and determined by flow cytometry, cell lysis method and live cell imaging using confocal laser scanning microscopy.

Results
The nanoemulsion showed a droplet size of 123.03 ± 2.1 nm and zeta potential of − 54.5 mV that changed because of the surface decoration with transferrin to 182.7 ± 0.2 and + 30.2 mV, respectively. Within the uptake studies utilizing flow cytometry, transferrin-conjugated nanoemulsion showed a 5.2-fold higher uptake in Caco-2 cells and twofold improvement in case of HeLa cells compared with unmodified formulation. The outcome was confirmed visually via live cell imaging.

Conclusion
According to the results, transferrin-conjugated nanoemulsion might be considered as a promising drug delivery system for a selective receptor-mediated drug delivery.
Effective and Universal Pre-Processing for Multi-Angle CHRIS/PROBA Images
Authors: Wang Qiang , Pang Yong , Jia Weiwei , Zhang Haowei , Wang Chaoyang 
Published: March 2021

AbstractCompared with traditional nadir observations, multi-angle hyperspectral remote sensing can obtain more spatial and spectral information and improve the inversion precision of structure information on the Earth’s surface. However, processing multi-angle remote-sensing images presents new challenges. Owing to the multi-angle sensors used to obtain multi-angle images, there are major differences in the spatial and spectral information between each angle in these images. Data from the Compact High-resolution Imaging Spectrometer (CHRIS) on Project for On-Board Autonomy (PROBA) should be pre-processed to extract the BRDF (Bidirectional Reflectance Distribution Functions). Given the limitations of the pre-processing software currently available for CHRIS/PROBA images, and the lack of metadata and auxiliary origin schedules, some CHRIS multi-angle images cannot be pre-processed correctly. In the study, to promote the application of multi-angle data, a formula for calculating key parameters according to in-orbit geometric imaging relationships is derived to design a multi-angle image process flow including image rollovers, bad-line repairs, orthorectification and atmospheric corrections accounting for terrain effects. Test results indicate that the pre-processing method can quickly and effectively recover multi-angle hyperspectral information and obtain spectral characteristics of multi-angle observations.
Attention in Skilled Behavior: an Argument for Pluralism
Authors: Dayer Alex , Jennings Carolyn Dicey 
Published: March 2021

AbstractPeak human performance—whether of Olympic athletes, Nobel prize winners, or you cooking the best dish you’ve ever made—depends on skill. Skill is at the heart of what it means to excel. Yet, the fixity of skilled behavior can sometimes make it seem a lower-level activity, more akin to the movements of an invertebrate or a machine. Peak performance in elite athletes is often described, for example, as “automatic” by those athletes: “The most frequent response from participants (eight athletes and one coach) when describing the execution of a peak performance was the automatic execution of performance” (Anderson et al. 2014). While the automaticity of skilled behavior is widely acknowledged, some worry that too much automaticity in skill would challenge its ability to exhibit human excellence. And so two camps have developed: those who focus on the automaticity of skilled behavior, the “habitualists,” and those who focus on the higher-level cognition behind peak performance, the “intellectualists.” We take a different tack. We argue that skilled behavior weaves together automaticity and higher-level cognition, which we call “pluralism.” That is, we argue that automaticity and higher-level cognition are both normal features of skilled behavior that benefit skilled behavior. This view is hinted at in other quotes about automaticity in skill—while expert gamers describe themselves as “playing with” automaticity (Taylor and Elam 2018), expert musicians are said to balance automaticity with creativity through performance cues: “Performance cues allow the musician to attend to some aspects of the performance while allowing others to be executed automatically” (Chaffin and Logan 2006). We describe in this paper three ways that higher-level cognition and automaticity are woven together. The first two, level pluralism and synchronic pluralism, are described in other papers, albeit under different cover. We take our contribution to be both distinguishing the three forms and contributing the third, diachronic pluralism. In fact, we find that diachronic pluralism presents the strongest case against habitualism and intellectualism, especially when considered through the example of strategic automaticity. In each case of pluralism, we use research on the presence or absence of attention (e.g., in mind wandering) to explore the presence or absence of higher-level cognition in skilled behavior.
Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry
Authors: van der Ploeg Phyllis , van Lieshout Laura A. M. , van de Stolpe Anja , Bosch Steven L. , Lentjes-Beer Marjolein H. F. M. , Bekkers Ruud L. M. , Piek Jurgen M. J. 
Published: March 2021

Abstract
Purpose
Anti-estrogen therapy may be used as a palliative treatment option in high-grade serous ovarian carcinomas (HGSC). However, clinical implementation is limited as the use of estrogen receptor (ER) protein expression by immunohistochemistry remains insufficient in predicting therapy response. To determine the accuracy of ER protein expression as a marker for ER signaling pathway activity, we aimed to correlate ER protein expression to functional ER signaling pathway activity in HGSC.

Methods
Immunohistochemical ER protein expression was visually scored using total percentages of stained tumor cells and histoscores. Subsequently, mRNA was extracted, and RT-qPCR analysis was performed. Functional ER pathway activity was assessed by a computational Bayesian model inferring ER signaling pathway activity from mRNA levels of ER-specific target genes.

Results
Our analysis of 29 HGSCs shows that neither total percentage of ER protein expression, nor ER histoscores are significantly correlated to ER signaling pathway activity (respectively, p = 0.473 and p = 0.606). Classification of HGSC into three groups based on ER histoscores 0–100 (n = 6), 101–200 (n = 15) and 201–300 (n = 8) resulted in comparable mean ER signaling pathway activity among the groups (p = 0.356). Several samples in the higher ER histoscore groups had low ER signaling pathway activity, indicating that nuclear ER protein expression is not sufficient to describe transcriptional ER activation.

Conclusion
Positive immunohistochemical ER staining is not always indicative of an active ER signaling pathway and is, therefore, a poor predictor of anti-estrogen response. Further research is needed to prove the predictive value of ER signaling pathway activity regarding anti-estrogen sensitivity in HGSC patients.
The Criteria to Qualify a Geographical Term as Generic: Are We Moving from a European to a US Perspective?
Authors: de Almeida Alberto Ribeiro , Carls Suelen 
Published: March 2021

AbstractThis article discusses the transformation of a distinctive trade sign into a generic term. Any distinctive trade sign carries this risk, primarily if it benefits from a high level of reputation or prestige, and the product identified is unique in the market. This is probably the most critical danger for such signs, especially if they are industrial property rights. Several criteria have been developed to determine if a sign has been transformed into a generic term. These criteria have economic and political relevance, as genericness is not a trivial issue. The European Court of Justice (ECJ) has taken a position in this matter, as have the European Union Regulations on trademarks and geographical indications. However, the bilateral and multilateral agreements are the critical arena for conflicts concerning geographical terms’ qualification as common terms. The European Union (EU) and the United States (US) have been in the spotlight for a long time, while China is also reaching a prominent place in this dispute. The most recent bilateral agreements have been twisting the criteria applied when assessing a geographical term’s genericness.
How great is the negative impact of masking and social distancing and how can we enhance communication skills in the elderly people?
Authors: Brotto Davide , Sorrentino Flavia , Agostinelli Anna , Lovo Elisa , Montino Silvia , Trevisi Patrizia , Favaretto Niccolò , Bovo Roberto , Martini Alessandro 
Published: March 2021

AbstractDuring COVID-19 pandemic, protective measures such as social distancing and face masks posed a challenge in daily communication, in this context the elderly are one of the most at risk categories as widely exposed to hearing loss. This article focuses on how the COVID-19 pandemic affected verbal communication, especially on those people that even in normal conditions present an increased difficulty in speech perception. Special attention has been paid to hearing aids and cochlear implant users, these devices indeed can be affected by a speech intelligibility reduction and could be uncomfortable if used together with face masks. Possible alternatives and solutions will be proposed to reduce the negative impacts of face coverings on communication, to enhance speech intelligibility and to manage wearability of hearing rehabilitation devices.