bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of p38 mitogen‐activated protein kinase signalling in virus replication and potential for developing broad spectrum antiviral drugs
Authors: Chander Yogesh , Kumar Ram , Khandelwal Nitin , Singh Namita , Shringi Brij Nandan , Barua Sanjay , Kumar Naveen 
Published: January 2021

SummaryMitogen‐activated protein kinases (MAPKs) play a key role in complex cellular processes such as proliferation, development, differentiation, transformation and apoptosis. Mammals express at least four distinctly regulated groups of MAPKs which include extracellular signal‐related kinases (ERK)‐1/2, p38 proteins, Jun amino‐terminal kinases (JNK1/2/3) and ERK5. p38 MAPK is activated by a wide range of cellular stresses and modulates activity of several downstream kinases and transcription factors which are involved in regulating cytoskeleton remodeling, cell cycle modulation, inflammation, antiviral response and apoptosis. In viral infections, activation of cell signalling pathways is part of the cellular defense mechanism with the basic aim of inducing an antiviral state. However, viruses can exploit enhanced cell signalling activities to support various stages of their replication cycles. Kinase activity can be inhibited by small molecule chemical inhibitors, so one strategy to develop antiviral drugs is to target these cellular signalling pathways. In this review, we provide an overview on the current understanding of various cellular and viral events regulated by the p38 signalling pathway, with a special emphasis on targeting these events for antiviral drug development which might identify candidates with broad spectrum activity.
Learning‐based robust neuro‐control: A method to compute control Lyapunov functions
Authors: Rego Rosana C. B. , de Araújo Fábio M. U. 
Published: January 2021

AbstractNonlinear dynamical systems play a crucial role in control systems because, in practice, all the plants are nonlinear, and they are also a hopeful description of complex robot movements. To perform a control and stability analysis of a nonlinear system, usually, a Lyapunov function is used. In this article, we proposed a method to compute a control Lyapunov function (CLF) for nonlinear dynamics based on a learning robust neuro‐control strategy. The procedure uses a deep neural network architecture to generate control functions supported by the Lyapunov stability theory. An estimation of the region of attraction is produced for advanced stability analysis. We implemented two numerical examples to compare the performance of the proposed technique with some existing methods. The proposed method computes a CLF that provides the stabilizability of the systems and produced better solutions to nonlinear systems in the design of stable controls without linear approximations and in the presence of disturbances.
Recognition and operationalization of Future‐Scaffolding Skills: Results from an empirical study of a teaching–learning module on climate change and futures thinking
Authors: Levrini Olivia , Tasquier Giulia , Barelli Eleonora , Laherto Antti , Palmgren Elina , Branchetti Laura , Wilson Caitlin 
Published: January 2021

AbstractThis article takes its point of departure from the younger generation's problematic relationship with time and the future. A general sense of changeability and directionlessness in society compromises young people's confidence in themselves to make a difference as individuals in important global issues affecting their futures, such as climate change. Given recent aims and commitments of science education to promote sustainable development and student agency, this study explores how science teaching can help students imagine and face possible future scenarios and develop agency in the present to influence them. This article presents a science education approach to equip secondary school students with skills of futures thinking and agency that we call “future‐scaffolding skills.” It also shows the process of building an operational definition for recognizing those skills in students' discourse and actions. For this purpose, an empirical study was carried out in the context of a teaching–learning module on climate change, consisting of activities inspired by the field of futures studies. Essays, individual and group interviews, questionnaires, and video recordings of students' final projects were collected from 24 students (16–19‐years old) from three European countries. The results contribute to operationally defining “future‐scaffolding skills,” consisting of “structural skills” (the ability to recognize temporal, logical and causal relationships and build systemic views) and “dynamical skills” (the ability to navigate scenarios, relating local details to global views, past to present and future, and individual to collective actions).
Multidimensional trajectories for understanding ecosystems
Authors: Eberbach Catherine , Hmelo‐Silver Cindy E. , Jordan Rebecca , Taylor Joseph , Hunter Roberta 
Published: January 2021

AbstractThis study examines how middle school students develop an increasingly coherent understanding of aquatic ecosystems. As part of a broader design research study that used Structure‐Behavior‐Function (SBF) theory as an organizing conceptual representation, we created two instructional units that focused on pond and aquarium environments. We coded and analyzed 70 middle school students' drawings of aquatic environments collected before, during, and after a technology‐rich instructional intervention. Coding considered several relations between multiple system levels: Macro‐Micro (MM), Biotic‐Abiotic (BA), and SBF. Hierarchical Linear Modeling analysis was used to examine the relationship within and between levels. This suggested that students followed multidimensional trajectories toward an increasingly coherent understanding of aquatic ecosystems (i.e., separately across the MM, BA, and SBF dimensions). Even so, the ability to observe phenomena at multiple MM and BA levels may be an underlying constraint to observing integrated SBF relations and the development of a more coherent understanding of ecosystems. We discuss implications for instruction and the design of learning environments.
Fourier‐transform infrared spectroscopy of biofluids: A practical approach
Authors: Theakstone Ashton G. , Rinaldi Christopher , Butler Holly J. , Cameron James M. , Confield Lily Rose , Rutherford Samantha H. , Sala Alexandra , Sangamnerkar Sayali , Baker Matthew J. 
Published: January 2021

AbstractBiofluid spectroscopy is an emerging technology in the field of clinical investigation, providing a simple way to extract diagnostic and observational information from easy to acquire samples. Infrared spectroscopy is well suited to analyse a large range of biofluid samples, including blood and its derivatives, due to flexible sampling modes and high sensitivity to subtle biological changes. As the technology advances towards the clinic, factors influencing successful clinical translation are becoming apparent. Here, we provide a tutorial for effective biofluid spectroscopy study design, discussing sample and instrument parameters, as well as clinical considerations. The aim is to present the current understanding of clinical translation in the field of biofluid spectroscopy, and to facilitate other clinical applications to advance to the clinic.image
Content knowledge and social factors influence student moral reasoning about CRISPR/Cas9 in humans
Authors: Seiter Katie M. , Fuselier Linda 
Published: January 2021

AbstractConsideration of socioscientific issues (SSIs) promotes the development of moral and sociocultural perspectives that encourage a rich understanding of the nature of science. The use of moral reasoning to approach SSIs is known to influence how students justify arguments and persuade others; less is known about how student moral reasoning is influenced by both content knowledge and demographic identities. We performed an exploratory study to investigate how students use moral reasoning when considering an SSI about the use of CRISPR/Cas9 technology for nonmedical enhancement in humans. Using content analysis, we examined written responses from 279 undergraduate students from three content knowledge levels and a variety of demographic populations (socioeconomic, gender, and first‐generation status). We identified instances of consequence and principle‐based moral reasoning and categorized commonly employed moral considerations under these broad themes. Students opposed nonmedical enhancement with CRISPR/Cas9 technology and perceived it as fraught with moral controversy primarily related to eugenics, equity, diversity, risk, and the authority of nature. Content knowledge level, gender, socioeconomic status, and first‐generation status influenced which moral considerations were employed by students and these carried interaction effects that indicate complex relationships between content knowledge level and demographic variables. We suggest more explicit instruction about complex societal issues linked to the history of science and genetic engineering, such as eugenics and inequity, and further investigation of moral perspectives for students from lower socioeconomic backgrounds and underrepresented groups so that these perspectives can be integrated into curricula to foster diverse classroom environments.
Severe tail lesions in finisher pigs are associated with reduction in annual profit in farrow‐to‐finish pig farms
Authors: van Staaveren Nienke , Boyle Laura Ann , Manzanilla Edgar García , O'Driscoll Keelin , Shalloo Laurence , Díaz Julia Adriana Calderón 
Published: January 2021

AbstractObjectives: We investigated the financial impact of different prevalence levels of severe tail lesions (STL) during the finisher stage associated with changes in average daily gain (ADG) in farrow‐to‐finish pig farms.Methods: Prevalence of STL was estimated for 31 farrow‐to‐finish pig farms. Regression tree analysis was used to identify a threshold for STL associated with differences in ADG. Then, a financial analysis was carried using the Teagasc Pig Production model.Results: A threshold of ≥0.86% prevalence of STL was associated with a 4.8% decrease in ADG which translated into pigs requiring 7 days more to reach target slaughter weight than in farms below the threshold. Reduced ADG meant that farms with higher prevalence of STL used 3.6% more weaner and 1.4% more finisher feed per year increasing feed costs by 1.5%. This reduced mean annual farm profit by 15.1% in farms with higher prevalence of STL.Conclusions: Our results provide an indication of the financial effects of STL in intensive pig production systems. The identified threshold for the prevalence of STL could provide a tangible target for farmers to focus on in developing strategies to reduce tail lesions and allow farmers to complete a cost benefit analysis of controlling STL.
Synthesis, structure and magnetic properties of a cobalt(II) mesoxalate 1D coordination polymer
Authors: Gil‐Hernández Beatriz , Sanchiz Joaquín 
Published: January 2021

AbstractMesoxalate ligand (H2mesox)2−, the conjugate base of the mesoxalic acid (2,2’‐dihydroxyl‐malonic acid) reacts with cobalt (II) ions to form the 1‐D coordination polymer {[Co(H2mesox)(H2O)2] ⋅ H2O}n. This compound displays a structure based on homochiral polymeric chains which stack together in an AABB fashion through hydrogen bonding by both coordination and crystallisation water molecules. Although the magnetic properties for such a Co(II) compound are difficult to interpret in the whole temperature range, at low temperatures the Co(II) behaves as an S=1/2 effective spin and equation derived by Fisher from the Ising model was applied to analyse the data in the 4–40 K range. The magnetic interactions in this compound are compared with the magnetic interactions displayed by similar compounds reported in the literature.
Regulatory Non-coding RNAs in Atherosclerosis
Authors: Schober Andreas , Maleki Saffiyeh Saboor , Nazari-Jahantigh Maliheh 
Published: January 2021

AbstractRegulatory RNAs like microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) control vascular and immune cells’ phenotype and thus play a crucial role in atherosclerosis. Moreover, the mutual interactions between miRNAs and lncRNAs link both types of regulatory RNAs in a functional network that affects lesion formation. In this review, we deduce novel concepts of atherosclerosis from the analysis of the current data on regulatory RNAs’ role in endothelial cells (ECs) and macrophages. In contrast to arterial ECs, which adopt a stable phenotype by adaptation to high shear stress, macrophages are highly plastic and quickly change their activation status. At predilection sites of atherosclerosis, such as arterial bifurcations, ECs are exposed to disturbed laminar flow, which generates a dysadaptive stress response mediated by miRNAs. Whereas the highly abundant miR-126-5p promotes regenerative proliferation of dysadapted ECs, miR-103-3p stimulates inflammatory activation and impairs endothelial regeneration by aberrant proliferation and micronuclei formation. In macrophages, miRNAs are essential in regulating energy and lipid metabolism, which affects inflammatory activation and foam cell formation.Moreover, lipopolysaccharide-induced miR-155 and miR-146 shape inflammatory macrophage activation through their oppositional effects on NF-kB. Most lncRNAs are not conserved between species, except a small group of very long lncRNAs, such as MALAT1, which blocks numerous miRNAs by providing non-functional binding sites. In summary, regulatory RNAs’ roles are highly context-dependent, and therapeutic approaches that target specific functional interactions of miRNAs appear promising against cardiovascular diseases.
Dark matter in minimal dimensional transmutation with multicritical-point principle
Authors: Hamada Yuta , Kawai Hikaru , Oda Kin-ya , Yagyu Kei 
Published: January 2021

Abstract
We investigate a model with two real scalar fields that minimally generates exponentially different scales in an analog of the Coleman-Weinberg mechanism. The classical scale invariance — the absence of dimensionful parameters in the tree-level action, required in such a scale generation — can naturally be understood as a special case of the multicritical-point principle. This two-scalar model can couple to the Standard Model Higgs field to realize a maximum multicriticality (with all the dimensionful parameters being tuned to critical values) for field values around the electroweak scale, providing a generalization of the classical scale invariance to a wider class of criticality. As a bonus, one of the two scalars can be identified as Higgs-portal dark matter. We find that this model can be consistent with the constraints from dark matter relic abundance, its direct detection experiments, and the latest LHC data, while keeping the perturbativity up to the reduced Planck scale. We then present successful benchmark points satisfying all these constraints: the mass of dark matter is a few TeV, and its scattering cross section with nuclei is of the order of 10−9 pb, reachable in near future experiments. The mass of extra Higgs boson H is smaller than or of the order of 100 GeV, and the cross section of e+e− → ZH can be of fb level for collision energy 250 GeV, targetted at future lepton colliders.
Nilpotence Varieties
Authors: Eager Richard , Saberi Ingmar , Walcher Johannes 
Published: January 2021

AbstractWe consider algebraic varieties canonically associated with any Lie superalgebra, and study them in detail for super-Poincaré algebras of physical interest. They are the locus of nilpotent elements in (the projectivized parity reversal of) the odd part of the algebra. Most of these varieties have appeared in various guises in previous literature, but we study them systematically here, from a new perspective: As the natural moduli spaces parameterizing twists of a super-Poincaré-invariant physical theory. We obtain a classification of all possible twists, as well as a systematic analysis of unbroken symmetry in twisted theories. The natural stratification of the varieties, the identification of strata with twists, and the action of Lorentz and R-symmetry are emphasized. We also include a short and unconventional exposition of the pure spinor superfield formalism, from the perspective of twisting, and demonstrate that it can be applied to construct familiar multiplets in four-dimensional minimally supersymmetric theories. In all dimensions and with any amount of supersymmetry, this technique produces BRST or BV complexes of supersymmetric theories from the Koszul complex of the maximal ideal over the coordinate ring of the nilpotence variety, possibly tensored with any equivariant module over that coordinate ring. In addition, we remark on a natural connection to the Chevalley–Eilenberg complex of the supertranslation algebra, and give two applications related to these ideas: a calculation of Chevalley–Eilenberg cohomology for the (2, 0) algebra in six dimensions, and a degenerate BV complex encoding the type IIB supergravity multiplet.
Attribution of autonomy and its role in robotic language acquisition
Authors: Förster Frank , Althoefer Kaspar 
Published: January 2021

AbstractThe false attribution of autonomy and related concepts to artificial agents that lack the attributed levels of the respective characteristic is problematic in many ways. In this article, we contrast this view with a positive viewpoint that emphasizes the potential role of such false attributions in the context of robotic language acquisition. By adding emotional displays and congruent body behaviors to a child-like humanoid robot’s behavioral repertoire, we were able to bring naïve human tutors to engage in so called intent interpretations. In developmental psychology, intent interpretations can be hypothesized to play a central role in the acquisition of emotion, volition, and similar autonomy-related words. The aforementioned experiments originally targeted the acquisition of linguistic negation. However, participants produced other affect- and motivation-related words with high frequencies too and, as a consequence, these entered the robot’s active vocabulary. We will analyze participants’ non-negative emotional and volitional speech and contrast it with participants’ speech in a non-affective baseline scenario. Implications of these findings for robotic language acquisition in particular and artificial intelligence and robotics more generally will also be discussed.
The nonlinear Schrödinger equation in the half-space
Authors: Fernández Antonio J. , Weth Tobias 
Published: January 2021

AbstractThe present paper is concerned with the half-space Dirichlet problem "Equation missing"where $$\mathbb {R}^{N}_{+}:= \{\,x \in \mathbb {R}^N: x_N > 0\, \}$$

R

+
N

:
=

{

x
∈

R

N

:

x
N

>
0

}

for some $$N \ge 1$$

N
≥
1

and $$p > 1$$

p
>
1

, $$c > 0$$

c
>
0

are constants. We analyse the existence, non-existence and multiplicity of bounded positive solutions to ($$P_c$$

P
c

). We prove that the existence and multiplicity of bounded positive solutions to ($$P_c$$

P
c

) depend in a striking way on the value of $$c > 0$$

c
>
0

and also on the dimension N. We find an explicit number $${c_p}\in (1,\sqrt{e})$$

c
p

∈

(
1
,

e

)

, depending only on p, which determines the threshold between existence and non-existence. In particular, in dimensions $$N \ge 2$$

N
≥
2

, we prove that, for $$0< c < {c_p}$$

0
<
c
<

c
p

, problem ($$P_c$$

P
c

) admits infinitely many bounded positive solutions, whereas, for $$c > {c_p}$$

c
>

c
p

, there are no bounded positive solutions to ($$P_c$$

P
c

).
Population pharmacokinetic modelling to quantify the magnitude of drug-drug interactions between amlodipine and antiretroviral drugs
Authors: Courlet Perrine , Guidi Monia , Alves Saldanha Susana , Cavassini Matthias , Stoeckle Marcel , Buclin Thierry , Marzolini Catia , Decosterd Laurent A. , Csajka Chantal 
Published: January 2021

Abstract
Purpose
Drug-drug interactions (DDIs) with antiretroviral drugs (ARVs) represent an important issue in elderly people living with HIV (PLWH). Amlodipine is a commonly prescribed antihypertensive drug metabolized by CYP3A4, thus predisposed to a risk of DDIs. Guidance on the management of DDIs is mostly based on theoretical considerations derived from coadministration with other CYP3A4 inhibitors. This study aimed at characterizing the magnitude of DDIs between amlodipine and ARV drugs in order to establish dosing recommendations.

Methods
A population pharmacokinetic analysis was developed using non-linear mixed effect modelling (NONMEM) and included 163 amlodipine concentrations from 55 PLWH. Various structural and error models were compared to characterize optimally the concentration-time profile of amlodipine. Demographic and clinical characteristics as well as comedications were tested as potential influential covariates. Model-based simulations were performed to compare amlodipine exposure (i.e. area under the curve, AUC) between coadministered ARV drugs.

Results
Amlodipine concentration-time profile was best described using a one-compartment model with first-order absorption and a lag-time. Amlodipine apparent clearance was influenced by both CYP3A4 inhibitors and efavirenz (CYP3A4 inducer). Model-based simulations revealed that amlodipine AUC increased by 96% when coadministered with CYP3A4 inhibitors, while efavirenz decreased drug exposure by 59%.

Conclusion
Coadministered ARV drugs significantly impact amlodipine disposition in PLWH. Clinicians should adjust amlodipine dosage accordingly, by halving the dosage in PLWH receiving ARV with inhibitory properties (mainly ritonavir-boosted darunavir), whereas they should double amlodipine doses when coadministering it with efavirenz, under appropriate monitoring of clinical response and tolerance.
Magnetic resonance imaging improves the prediction of tumor staging in localized prostate cancer
Authors: Valentin B. , Schimmöller L. , Ullrich T. , Klingebiel M. , Demetrescu D. , Sawicki L. M. , Lakes J. , Mally D. , Quentin M. , Esposito I. , Albers P. , Antoch G. , Arsov C. 
Published: January 2021

Abstract
Objectives
The aim of this study was to investigate 3 Tesla multiparametric magnetic resonance imaging (mpMRI)-based predictors for the pretherapeutic T staging of prostate cancer and their accuracy.

Methods
Consecutive patients with 3 Tesla mpMRI, positive systematic and MR-targeted biopsy, and subsequent radical prostatectomy (RPE) between 01/2016 and 12/2017 were included. MRI parameters such as measurable extraprostatic extension (EPE) (≥ 3 mm), length of (pseudo)capsular contact (LCC), invasion of neurovascular bundle (NVBI), and/or seminal vesicles lesion contact (SVC) or infiltration (SVI) were assessed and correlated to clinical and histopathological results.

Results
136 men were included. In 76 cases, a pT2 stage was determined, in 29 cases a pT3a, and in 31 a pT3b stage. The positive and negative predictive values (PPV, NPV) for the detection of T3 by measurable EPE on MRI was 98% (CI 0.88–1) and 81% (CI 0.72–0.87). No visible NVBI was found in pT2 patients (NPV 100%; CI 0.95–1). ROC analysis for T3a prediction with LCC (AUC 0.81) showed a sensitivity of 87% and a specificity of 62% at a threshold of 12.5 mm (J = 0.485) and 93% and 58% at 11 mm (Jmax = 0.512). All patients with pT3a had a LCC > 5 mm. In case of pT3b, 29/31 patients showed a SVC (PPV 76%, CI 0.61–0.87; NPV 98%, CI 0.93–0.99), and 23/31 patients showed a SVI (PPV 100%, CI 0.86–1; NPV 93%, CI 0.87–0.96). EPE (p < 0.01), LCC (p = 0.05), and SVC (p = 0.01) were independent predictors of pT3.

Conclusions
MRI-measurable EPE, LCC, and SVC were reliable, independent, preoperative predictors for a histopathological T3 stage. A LCC ≥ 11 mm indicated a pT3a stage, whereas a LCC < 5 mm excluded it. On MRI, visible SVI or even SVC of the PCa lesion was reliable preoperative predictors for a pT3b stage.