bluuebunny/crossref_metadata_2025_split huggingface dataset:
Krankheitsmodifizierende Therapieansätze bei der Huntington-Krankheit
Authors: Frank Wiebke , Lindenberg Katrin S. , Mühlbäck Alzbeta , Lewerenz Jan , Landwehrmeyer G. Bernhard 
Published: November 2021

ZusammenfassungDie Huntington-Krankheit (HK) ist die häufigste monogenetische neurodegenerative Erkrankung und kann bereits im präklinischen Stadium zweifelsfrei diagnostiziert werden, zumindest in allen Fällen, bei denen die CAG-Expansionsmutation im Huntingtin-Gen (HTT) im Bereich der vollen Penetranz liegt. Wichtige Voraussetzungen für eine früh im Krankheitsprozess einsetzende und deshalb den weiteren Verlauf der Krankheit in klinisch relevanter Weise modifizierende Therapie sind damit gegeben und machen die HK zu einer Modellerkrankung für neuroprotektive Behandlungsansätze. In der Vergangenheit lag der Schwerpunkt auf dem Ausgleich vermuteter Neurotransmitterdefizite (GABA) analog zur Parkinson-Erkrankung und auf klassischen neuroprotektiven Strategien zur Beeinflussung hypothetischer gemeinsamer Endstrecken neurodegenerativer Erkrankungen (z. B. Exzitotoxizität, mitochondriale Dysfunktion, oxidativer Stress etc.). Mit der Entdeckung der krankheitsverursachendenHTT-Mutation im Jahr 1993 fokussierte sich die Therapieforschung zunehmend darauf, soweit proximal wie möglich in die pathophysiologische Ereigniskette einzugreifen. Ein wichtiger Ansatzpunkt ist hier dieHTT-mRNA mit dem Ziel, die Nachproduktion mutierter Huntingtin-Genprodukte zu senken und damit den Körper von deren schädigenden Auswirkungen zu entlasten; zu diesem Zweck sind verschiedene Behandlungsmodalitäten (einzelsträngige DNA und RNA, divalente RNA und Zinkfinger-Repressorkomplexe, oral verfügbare Spleißmodulatoren) entwickelt worden, die sich in der klinischen Prüfung (Phase I–III) oder in späten Stadien der präklinischen Entwicklung befinden. Zudem zeichnet sich ab, dass es möglich sein könnte, die Länge der somatisch instabilen, d. h. über die Lebenszeit v. a. im Hirngewebe zunehmende CAG-Mutation selbst zu beeinflussen und die Progression der HK hierdurch zu bremsen.
Industry 4.0, transition or addition in SMEs? A systematic literature review on digitalization for deviation management
Authors: Chavez Zuhara , Hauge Jannicke Baalsrud , Bellgran Monica 
Published: November 2021

AbstractNowadays, Industry 4.0 (I4.0) has become a trendy topic in manufacturing industries worldwide. The definition is far from being comprehensible for small players, and the practical uptake is ambiguous. Transnational companies are often at the top in deploying I4.0 features, learning primarily from their experimentation. Alternatively, small- to medium-sized enterprises (SMEs), given their less stable value chains and unsteady processes, tend to target most of their efforts on controlling disturbances and adopting solutions for deviation control. Such solutions can be features that set the path for SMEs to transition to I4.0. This paper aims to examine the reported degree of digitalization in implemented solutions in SMEs when handling deviations and analyze the integration of such solutions in their digital transformation process. Systematic literature review (SLR) is used to examine literature published up to and including January 2019. The results show a higher concentration on practical applications rather than on frameworks. Existing frameworks that focus on SMEs address particular elements of I4.0 rather than a gradual shift with a holistic view, increasing the deployment difficulty for SMEs. This paper identifies potential constraints in deployment if such a trend maintains for consecutive years.
Dolomitization of Late Norian carbonate deposits of restricted basin facies in the Keszthely Mts., Transdanubian Range, Hungary
Authors: Haas János , Budai Tamás , Hips Kinga , Czuppon György , Győri Orsolya , Horváth Anikó , Héja Gábor 
Published: November 2021

AbstractIn the Transdanubian Range (Hungary), a wide spectrum of Triassic dolomites is known. Mechanism of dolomitization of the platform carbonate successions was subject of a number of studies but the study of dolomitization of basinal carbonates is very limited. Petrographical and isotope–geochemical characteristics of the Upper Triassic dolomitized carbonate deposits, formed in a fault-controlled intraplatform basin, and interpretation of the dolomite-forming processes are presented in the current paper. From the latest Carnian to Middle Norian under semi-arid climatic conditions density-driven flux of seawater derived mesohaline fluids was the dominant mechanism of the near-surface pervasive dolomitization of the thick platform carbonate succession. In the late Middle Norian incipient rifting of the Alpine Tethys led to establishment of an extensional structural regime and onset of the formation of the Kössen Basin. In the study area, above the dolomitized platform carbonate succession, platform-derived carbonate sediments were accumulated in a fault-bounded, semi-restricted sub-basin of the Kössen Basin, whereas talus breccias and debrites were deposited near a basin-bounding master fault. The basin deposits (lower and upper members of the Rezi Dolomite Formation) were subject of early diagenetic dolomitization in shallow burial setting. Enhanced salinity seawater was the dolomitizing fluid; the synsedimentary fracturing may have promoted the fluid flow and thereby the dolomitization. Thick-bedded carbonates (middle member of the Rezi Dolomite Formation) representing a progradational tongue of the ambient platform are intercalated between the basin deposits. The dolomitization of this unit can be explained by the reflux model.
Morphing of soft tubes by anisotropic growth
Authors: Nardinocchi Paola , Teresi Luciano 
Published: November 2021

AbstractWe present a study of smart growth in layered cylindrical structures. We start from the characterization of a compatible growth field in an anisotropic growing tube with the aim to show a small perturbation in the compatible growth field that may produce a controlled deprivation of compatibility and localization of elastic energy storage in a composite structure made up of anisotropic growing tubes.
Robustness and static-positional accuracy of the SteamVR 1.0 virtual reality tracking system
Authors: Sansone Lucia Grazia , Stanzani Ronny , Job Mirko , Battista Simone , Signori Alessio , Testa Marco 
Published: November 2021

AbstractThe use of low-cost immersive virtual reality systems is rapidly expanding. Several studies started to analyse the accuracy of virtual reality tracking systems, but they did not consider in depth the effects of external interferences in the working area. In line with that, this study aimed at exploring the static-positional accuracy and the robustness to occlusions inside the capture volume of the SteamVR (1.0) tracking system. To do so, we ran 3 different tests in which we acquired the position of HTC Vive PRO Trackers (2018 version) on specific points of a grid drawn on the floor, in regular tracking conditions and with partial and total occlusions. The tracking system showed a high inter- and intra-rater reliability and detected a tilted surface with respect to the floor plane. Every acquisition was characterised by an initial random offset. We estimated an average accuracy of 0.5 ± 0.2 cm across the entire grid (XY-plane), noticing that the central points were more accurate (0.4 ± 0.1 cm) than the outer ones (0.6 ± 0.1 cm). For the Z-axis, the measurements showed greater variability and the accuracy was equal to 1.7 ± 1.2 cm. Occlusion response was tested using nonparametric Bland–Altman statistics, which highlighted the robustness of the tracking system. In conclusion, our results promote the SteamVR system for static measures in the clinical field. The computed error can be considered clinically irrelevant for exercises aimed at the rehabilitation of functional movements, whose several motor outcomes are generally measured on the scale of metres.
Spatio-temporal variation in stable isotope and elemental composition of key-species reflect environmental changes in the Baltic Sea
Authors: Liénart Camilla , Garbaras Andrius , Qvarfordt Susanne , Walve Jakob , Karlson Agnes M. L. 
Published: November 2021

AbstractCarbon and nitrogen stable isotope ratios are increasingly used to study long-term change in food web structure and nutrient cycling. We retrospectively analyse elemental composition (C, N and P) and stable isotopes (δ13C, δ15N) in archived monitoring samples of two important taxa from the bottom of the food web; the filamentous ephemeral macroalgae Cladophora spp. and the blue mussel Mytilus edulis trossulus from three contrasting regions in the Baltic Sea (coastal Bothnian Sea and Baltic Proper, open sea central Baltic). The aim is to statistically link the observed spatial and interannual (8–24 years’ time-series) variability in elemental and isotope baselines with their biomass trends and to the oceanographic monitoring data reflecting the ongoing environmental changes (i.e., eutrophication and climate) in this system. We find clear differences in isotope baselines between the two major Baltic Sea basins. However, the temporal variation in Mytilus δ13C was similar among regions and, at the open sea station, mussels and algae δ13C also correlated over time, likely reflecting a global (Suess) effect, whereas δ15N of both taxa varied with local and regional dissolved nitrogen concentrations in water. δ15N in source amino acids allowed detection of diazotrophic N in Mytilus, which was masked in bulk δ15N. Finally, Cladophora N:P reflected regional nutrient levels in the water while P%, which differed for both taxa, was linked to food quality for Mytilus. This study highlights the potential of a multi-taxa and multi-stable isotope approach to understand nutrient dynamics and monitor long-term environmental changes.
A continuum of hate: delimiting the field of hate studies
Authors: Schweppe Jennifer , Perry Barbara 
Published: November 2021

AbstractA relatively nascent discipline, the field of hate studies has been explored and theorised from a multiplicity of disciplinary contexts. However, the field is ill-defined, and the relationship between hate crime and other related concepts unexplored. Here, we consider the range of phenomena which might fall within or without the field of hate studies, initiating a discussion of the boundaries of the field. We signal both the continuities and discontinuities among and between an array of strategies intended to sort and maintain hierarchical relationships, with the purpose of provoking scholars in the field of hate studies to reflect on its scope.
A novel 5-ring multifocal electroretinography stimulus for detecting hydroxychloroquine retinal toxicity
Authors: Tsang Adrian , Kanda Pushpinder , Gottlieb Chloe , Virgili Gianni , Kantungane Lynca , Coupland Stuart 
Published: November 2021

Abstract
Purpose
Multifocal electroretinogram (mfERG) shows great utility as a screening tool to detect early hydroxychloroquine (HCQ) retinopathy, but its widespread use is limited by the lack of accessibility and long test duration. In this study, we evaluated a novel concentric 5-ring mfERG stimulus to provide a simplified and rapid protocol for screening HCQ toxicity.

Methods
Patients referred for HCQ retinopathy screening were consented to this observational cross-sectional study. Patients with amblyopia, high refractive error (more than 8 diopters), other retinal diseases precluding appropriate evaluation or history of retinal surgery were excluded. The data were collected from patients undergoing HCQ screening at a single center from July 2019 to March 2020. Patients were tested with the new concentric 5-ring mfERG stimulus, standard 61-hexagon mfERG stimulus, spectral domain optical coherence tomography and automated 10-2 visual fields. For the main outcome, the 5-ring mfERG was compared to 61-hexagon stimulus to determine the time-to-test completion and assess the association between ring (R1–R5) amplitude and ring ratio compared against cumulative dose, dose by real body weight and duration of therapy using Pearson correlation.

Results
In total, 52 patients (104 eyes; 5 males and 47 females) were recruited with a mean age of 59 years (range 23–85 years). The 5-ring protocol was markedly quicker to perform (1.3 ± 0.2 min; mean (SD)) compared to the 61-hexagon protocol (5.2 ± 0.6 min), p < 0.0001; n = 10 patients. The new R2/R5 ring ratio showed a moderate correlation with daily dose (r = − 0.640), cumulative dose (r = − 0.581) and duration of therapy (r = − 0.417). Similar correlations were observed with the new R2/R4 ring ratio which were not significantly different from the new R2/R5 correlation coefficients. The new R2/R5 ring ratio demonstrated a stronger correlation with daily (p = 0.002) and cumulative dose (p = 0.0001) compared to the 61-hexagon stimulus.

Conclusions
In this exploratory study, our novel 5-ring mfERG protocol significantly shortened data acquisition time while providing comparable results to the standard 61-hexagon stimulus for detecting HCQ-induced electrophysiological changes that are correlated with HCQ dosages and treatment duration. Our protocol has the potential to be more clinically practical by simplifying routine screening.
The Puppy in the Pit: Osteobiography of an Eighteenth-Century Dog at the Three Cranes Tavern, Massachusetts
Authors: Quinlan Liz M. 
Published: November 2021

AbstractBoston’s “Big Dig” construction project resulted in the excavation of multiple archaeological sites dating from the seventeenth to nineteenth centuries, including the Great House/Three Cranes Tavern in Charlestown, Massachusetts (USA). An otherwise unremarkable pit below the tavern foundation contained bones originally identified as a cat skeleton, which has subsequently been reidentified as a dog. This paper discusses site context, osteological evidence for the dog’s reclassification, and the shifts in cultural meaning this may indicate. Employing an osteobiographical approach, it draws together points of connection between the modern skeletal assessment, a series of 1980s excavations, and the motivations of eighteenth-century tavern inhabitants.
Socio-economic and spatial determinants of municipal cultural spending
Authors: Getzner Michael 
Published: November 2021

AbstractThe determinants of the expenditure of Austrian municipalities for cultural affairs are ascertained in a panel time series framework. The Austrian municipalities spend about € 93 per capita a year for cultural affairs (approximately 4% of the total municipal expenditure). The econometric estimations revealed that the size of the municipality, and various socio-economic, fiscal and political variables, are the main determinants of municipal cultural spending. The results of the estimations infer a rather small but nevertheless significant spatial dependence of cultural spending. An increase of 10% of cultural spending in the neighboring regions leads to an increase of 0.6–1.5% in a representative municipality (however, the potentially overlapping and contradicting reasons for spatial correlations could not be disentangled in this paper). In comparison to the spatial effects, the size of the municipality is a more significant predictor of municipal cultural spending. The larger cities provide many cultural goods and services to the surrounding areas by utilizing economies of scale and density. It can be concluded that municipalities, in particular in rural areas, should increase their efforts for co-operation in order to improve the efficiency of cultural spending.
Translation initiation from sequence variants of the bacteriophage T7 g10RBS in Escherichia coli and Agrobacterium fabrum
Authors: Benedict Alex B. , Chamberlain Joshua D. , Calvopina Diana G. , Griffitts Joel S. 
Published: November 2021

Abstract
Background
The bacteriophage T7 gene 10 ribosome binding site (g10RBS) has long been used for robust expression of recombinant proteins in Escherichia coli. This RBS consists of a Shine–Dalgarno (SD) sequence augmented by an upstream translational “enhancer” (Enh) element, supporting protein production at many times the level seen with simple synthetic SD-containing sequences. The objective of this study was to dissect the g10RBS to identify simpler derivatives that exhibit much of the original translation efficiency.

Methods and results
Twenty derivatives of g10RBS were tested using multiple promoter/reporter gene contexts. We have identified one derivative (which we call “CON_G”) that maintains 100% activity in E. coli and is 33% shorter. Further minimization of CON_G results in variants that lose only modest amounts of activity. Certain nucleotide substitutions in the spacer region between the SD sequence and initiation codon show strong decreases in translation. When testing these 20 derivatives in the alphaproteobacterium Agrobacterium fabrum, most supported strong reporter protein expression that was not dependent on the Enh.

Conclusions
The g10RBS derivatives tested in this study display a range of observed activity, including a minimized version (CON_G) that retains 100% activity in E. coli while being 33% shorter. This high activity is evident in two different promoter/reporter sequence contexts. The array of RBS sequences presented here may be useful to researchers in need of fine-tuned expression of recombinant proteins of interest.
Untargeted Metabolomic Profiling Reveals Variation in Metabolites Associated with Nutritional Values in Tef Accessions
Authors: Girija Aiswarya , Yadav Rattan , Corke Fiona , Doonan John , Mur Luis A. J. 
Published: November 2021

Abstract
Tef (Eragrostis tef), is a gluten-free orphan cereal, crop of nutritional and economical significance. Here we used untargeted metabolomics to survey metabolite variation in 14 diverse tef accessions at 15-days post germination. Tef genotypes were classified into four metabolomic groups where variation was linked to flavones and flavonols. Further analysis on white seeded accessions shows variation related to sucrose and important vitamins, nicotinamides (vitamin B3) riboflavin (vitamin B2) and folate (vitamin B9). Coloured seeded accessions showed variation in metabolism related to amino acid and sugars. This study highlights the potential of metabolomics in exploring the nutritional traits in tef.
The dynamical essence of powers
Authors: Roselli Andrea , Austin Christopher 
Published: November 2021

AbstractPowers are properties defined bywhat they do. The focus of the large majority of the powers literature has been mainly put on explicating the (multifaceted) results of the production of a power in certain (multifaceted) initial conditions: but all this causal complexity is bound to be—and, in fact, it has proved to be—quite difficult to handle. In this paper we take a different approach by focusing on the veryactivityof producing those multifaceted manifestations themselves. In this paper, we propose an original account of what the essence of a power consists in which stems from a radical reconceptualisation of power-causation according to which counterfactuals are to be explained away by powers, and not vice-versa. We call this approach thedynamical operator accountof powers. According to this account, the causal role of powers consists in their ensuring that the ontological transition from a stimulus S to a manifestation M happens. Powers thus have a dynamical essence which consists in the fundamental activity of generating the counterfactuals typically associated with them. We show that if one conceptualises this functional activity as the metaphysical fulcrum around which counterfactual-based causation revolves, one is granted not only an improved methodology to individuate powers but also a better understanding of their knowability, modality and directedness.
Development and validation of an analytical method for the determination of direct oral anticoagulants (DOAC) and the direct thrombin-inhibitor argatroban by HPLC–MS/MS
Authors: Brückner Lea , Beyer-Westendorf Jan , Tiebel Oliver , Pietsch Jörg 
Published: November 2021

AbstractSince direct oral anticoagulants (DOAC) are administered frequently to an elderly, co-morbid population, medical emergencies including trauma, acute bleeding or organ failure are not uncommon. In these situations, the type, dosage or the time of last intake of anticoagulants is often unknown and single substance analysis by functional tests is only possible if the substance contained in the sample is known. A reliable and validated toxicology screen of DOAC and argatroban would be helpful inform not only attending physicians in the emergency department but also law enforcement and courts of justice. After precipitation with acetone, HPLC separation was achieved on a Phenomenex Luna Pentafluorophenyl Colum using acetonitrile–water (90:10, v/v) as mobile phase system. Detection was performed using a 3200 Q Trap mass spectrometer (AB Sciex). For analysis MRM Scans (MS/MS) with positive ionization were chosen. The method was validated for blank serum as the matrix of choice. Limits of detection are between 0.5 and 1.0 ng/mL, limits of quantification are between 1.9 and 3.6 ng/mL and recoveries are above 60%. The applicability of the method was demonstrated by the determination of DOAC in body fluids from forensic cases and in therapeutic drug monitoring. The rapid simultaneous detection and quantification of apixaban, argatroban, dabigatran etexilate, dabigatran, edoxaban and rivaroxaban in body fluids by HPLC–MS/MS closes an important gap in emergency toxicology.
Activation-Inhibition dynamics of the oscillatory bursts of the human EEG during resting state. The macroscopic temporal range of few seconds
Authors: Gómez Carlos M. , Angulo-Ruíz Brenda Y. , Muñoz Vanesa , Rodriguez-Martínez Elena I. 
Published: November 2021

AbstractThe ubiquitous brain oscillations occur in bursts of oscillatory activity. The present report tries to define the statistical characteristics of electroencephalographical (EEG) bursts of oscillatory activity during resting state in humans to define (i) the statistical properties of amplitude and duration of oscillatory bursts, (ii) its possible correlation, (iii) its frequency content, and (iv) the presence or not of a fixed threshold to trigger an oscillatory burst. The open eyes EEG recordings of five subjects with no artifacts were selected from a sample of 40 subjects. The recordings were filtered in frequency ranges of 2 Hz wide from 1 to 99 Hz. The analytic Hilbert transform was computed to obtain the amplitude envelopes of oscillatory bursts. The criteria of thresholding and a minimum of three cycles to define an oscillatory burst were imposed. Amplitude and duration parameters were extracted and they showed durations between hundreds of milliseconds and a few seconds, and peak amplitudes showed a unimodal distribution. Both parameters were positively correlated and the oscillatory burst durations were explained by a linear model with the terms peak amplitude and peak amplitude of amplitude envelope time derivative. The frequency content of the amplitude envelope was contained in the 0–2 Hz range. The results suggest the presence of amplitude modulated continuous oscillations in the human EEG during the resting conditions in a broad frequency range, with durations in the range of few seconds and modulated positively by amplitude and negatively by the time derivative of the amplitude envelope suggesting activation-inhibition dynamics. This macroscopic oscillatory network behavior is less pronounced in the low-frequency range (1–3 Hz).