bluuebunny/crossref_metadata_2025_split huggingface dataset:
Splicing predictions, minigene analyses, and ACMG‐AMP clinical classification of 42 germline PALB2 splice‐site variants
Authors: Valenzuela‐Palomo Alberto , Bueno‐Martínez Elena , Sanoguera‐Miralles Lara , Lorca Víctor , Fraile‐Bethencourt Eugenia , Esteban‐Sánchez Ada , Gómez‐Barrero Susana , Carvalho Sara , Allen Jamie , García‐Álvarez Alicia , Pérez‐Segura Pedro , Dorling Leila , Easton Douglas F , Devilee Peter , Vreeswijk Maaike PG , de la Hoya Miguel , Velasco Eladio A 
Published: November 2021

AbstractPALB2 loss‐of‐function variants confer high risk of developing breast cancer. Here we present a systematic functional analysis of PALB2 splice‐site variants detected in approximately 113,000 women in the large‐scale sequencing project Breast Cancer After Diagnostic Gene Sequencing (BRIDGES; https://bridges-research.eu/). Eighty‐two PALB2 variants at the intron‐exon boundaries were analyzed with MaxEntScan. Forty‐two variants were selected for the subsequent splicing functional assays. For this purpose, three splicing reporter minigenes comprising exons 1–12 were constructed. The 42 potential spliceogenic variants were introduced into the minigenes by site‐directed mutagenesis and assayed in MCF‐7/MDA‐MB‐231 cells. Splicing anomalies were observed in 35 variants, 23 of which showed no traces or minimal amounts of the expected full‐length transcripts of each minigene. More than 30 different variant‐induced transcripts were characterized, 23 of which were predicted to truncate the PALB2 protein. The pathogenicity of all variants was interpreted according to an in‐house adaptation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG‐AMP) variant classification scheme. Up to 23 variants were classified as pathogenic/likely pathogenic. Remarkably, three ±1,2 variants (c.49‐2A>T, c.108+2T>C, and c.211+1G>A) were classified as variants of unknown significance, as they produced significant amounts of either in‐frame transcripts of unknown impact on the PALB2 protein function or the minigene full‐length transcripts. In conclusion, we have significantly contributed to the ongoing effort of identifying spliceogenic variants in the clinically relevant PALB2 cancer susceptibility gene. Moreover, we suggest some approaches to classify the findings in accordance with the ACMG‐AMP rationale. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd on behalf of The Pathological Society of Great Britain and Ireland.
A new strategy to reconcile amyloid cross‐seeding and amyloid prevention in a binary system of α‐synuclein fragmental peptide and hIAPP
Authors: Tang Yijing , Zhang Dong , Liu Yonglan , Zhang Yanxian , Zhou Yifan , Chang Yung , Zheng Bowen , Xu Alice , Zheng Jie 
Published: December 2021

AbstractAmyloid cross‐seeding and amyloid inhibition are two different research subjects being studied separately for different pathological purposes, in which amyloid cross‐seeding targets to study the co‐aggregation of different amyloid proteins and potential molecular links between different neurodegenerative diseases, while amyloid inhibition aims to design different molecules for preventing amyloid aggregation. While both amyloid cross‐seeding and amyloid inhibition are critical for better understanding the pathological causes of different neurodegenerative diseases including Parkinson disease (PD) and Type 2 diabetes (T2D), less efforts have been made to reconcile the two phenomena. Herein, we proposed a new preventive strategy to demonstrate (a) the cross‐seeding of octapeptide TKEQVTNV from α‐synuclein (associated with PD) with hIAPP (associated with T2D) and (b) the cross‐seeding‐promoted hIAPP fibrillization and cross‐seeding‐reduced hIAPP toxicity. Collective results confirmed that TKEQVTNV can indeed cross‐seed with hIAPP monomers and oligomers, not protofibrils, to form β‐structure‐rich fibrils and to accelerate hIAPP fibrillization. Moreover, such cross‐seeding‐induced promotion effect by TKEQVTNV also rescued the pancreatic cells from hIAPP‐induced cytotoxicity by increasing cell viability and reducing cell apoptosis simultaneously. This work provides a new angle to discover amyloid fragments and use them as amyloid modulators (inhibitors or promotors) to interfere with amyloid aggregation of other amyloid proteins, as well as sequence/structure basis to explore the amyloid cross‐seeding between different amyloid proteins that may help explain a potential molecular talk between different neurodegenerative diseases.
A new enabling variational inference model for approximating measurement likelihood in filtering nonlinear system
Authors: Ma Zhengya , Wang Xiaoxu , Liu Mingyong , Wang Lixin , Gao Pu , Yan Gongmin 
Published: December 2021

AbstractThis article considers the filtering problem with nonlinear measurements. We propose a new enabling variational inference model for approximating measurement likelihood, which is constructed by a linear Gaussian regression process. The resulting filter is referred to as the new enabling variational inference filter (NEVIF). In variational inference framework, the NEVIF obtains the variational posterior of state by minimizing the Kullback–Leibler divergence between the variational distribution and the true posterior. Then, the accuracy improvement and robustness of the NEVIF compared with the traditional methods are analyzed. Furthermore, an evaluation rule called the filtering evidence lower bound is developed to analyze the estimation accuracy performance of filters. Finally, the efficiency and superiority of the proposed filters compared with some existing filters are shown in numerical simulations.
Melanogenic Effect of Dersimelagon (Mt-7117), a Novel Oral Melanocortin 1 Receptor Agonist
Authors: Suzuki T. , Kawano Y. , Matsumoto A. , Kondo M. , Funayama K. , Tanemura S. , Miyashiro M. , Nishi A. , Yamada K. , Tsuda M. , Sato A. , Morokuma K. , Yamamoto Y. 
Published: November 2021

Abstract

Background
The activation of melanocortin 1 receptor (MC1R) on melanocytes stimulates the production of eumelanin. A tridecapeptide α melanocyte-stimulating hormone (αMSH) is known to induce skin pigmentation.

Objectives
We characterised the properties of a novel oral MC1R agonist dersimelagon (MT-7117) with respect to its specific binding to MC1R, downstream signalling and eumelanin production in experimental models.

Methods
The competitive binding and production of intracellular cyclic adenosine 3′, 5′-monophosphate in cells expressing recombinant melanocortin receptors were examined. A mouse melanoma cell line B16F1 was used for the evaluation of in vitro melanin production. The in vitro activity of MT-7117 was determined with αMSH and [Nle4, D-Phe7]-αMSH (NDP-αMSH) as reference comparators. The change of coat colour and skin pigmentation were evaluated after repeat administration of MT-7117 by oral gavage to C57BL/6J-Ay/+ mice and cynomolgus monkeys, respectively.

Results
MT-7117 showed the highest affinity for human MC1R compared to the other melanocortin receptors evaluated and agonistic activity for human, cynomolgus monkey and mouse MC1R, with EC50 values in the nanomolar range. In B16F1 cells, MT-7117 increased melanin production in a concentration-dependent manner. In vivo, MT-7117 (≥0.3 mg/kg/day p.o.) significantly induced coat colour darkening in mice. MT-7117 (≥1 mg/kg/day p.o.) induced significant skin pigmentation in monkeys and complete reversibility was observed after cessation of its administration.

Conclusions
MT-7117 is a novel oral MC1R agonist that induces melanogenesis in vitro and in vivo, suggesting its potential application for the prevention of phototoxic reactions in patients with photodermatoses, such as erythropoietic protoporphyria and X-linked protoporphyria.
2D Arsenene and Arsenic Materials: Fundamental Properties, Preparation, and Applications
Authors: Hu Yi , Liang Junchuan , Xia Yuren , Zhao Cheng , Jiang Minghang , Ma Jing , Tie Zuoxiu , Jin Zhong 
Published: November 2021

AbstractAs emerging 2D materials, arsenene and arsenic materials have attracted rising interest in the past few years. The diverse crystalline phases, exotic electrical characteristics, and widespread applications of 2D arsenene and arsenic bring them great research value and utilization potential. Herein, the recent progress of 2D arsenene and arsenic is reviewed in terms of fundamental properties, preparation, and applications. The fundamental properties of 2D arsenene and arsenic, including the crystal phases, environmental stability, and electrical structure, from theoretical to experimental reports are first summarized. Then, the experimental processes for preparing 2D arsenene and arsenic, along with their respective advantages and disadvantages, are introduced including epitaxial growth, mechanical exfoliation, and liquid‐phase exfoliation. Moreover, applications of 2D arsenene and arsenic are discussed, suggesting a wide range of applications of 2D arsenene and arsenic in field‐effect transistors, sensors, catalysts, biological applications, and so on. Finally, some perspectives about the challenges and opportunities of promising 2D arsenene and arsenic are provided. This review provides a helpful guidance and stimulates more focus on future explorations and developments of 2D arsenene and arsenic.
Systematic Evaluation and Studies on the Effect of Octenyl Succinic Anhydride Treatment on Structural, Functional, Morphological, and Flow Properties of Underutilized Chenopodium album Starch
Authors: Singh Renuka , Singh Sukhcharn , Saxena D.C. 
Published: November 2021

AbstractThe Chenopodium album starch is isolated and further modified by using different octenyl succinic anhydride (OSA) concentrations (1%, 2%, 3%) in slightly acidic and alkaline conditions (pH = 5, 6, 8, 9). The modification of starch significantly reduces amylose content as well as functional properties viz. solubility, swelling power, water, and oil absorption capacity. The higher compressibility is found in native starch (35.32%) as compared to modified starch (17.42% at pH 9) as elucidated from Carr's index indicating very poor and fair relative flowability, respectively. The decline in the cohesive nature of native starch is also detected from the reduced caking strength (1072.03 to 367.23 g mm) and cohesion index (15.37 to 11.37 mm) after modification. Modified starch also reflects a rise in pasting temperature from 80.05 to 87.10°C. SEM images and X‐ray diffraction reveals the development of regular‐shaped and larger starch particles and an increase in peak intensity. Overall, the present findings confirm that OSA treatment significantly increases the flowability to fair flow compared to native starch's cohesive nature.
Electrical Treeing Breakdown Characteristics of Epoxy/TiO2 Nanocomposites Influenced by Aggregates of Nano‐Sized TiO2
Authors: Murakami Yoshinobu , Yamada Daichi , Kodama Norihiko , Kawashima Tomohiro , Hozumi Naohiro , Yoshida Shigeyoshi , Umemoto Takahiro , Mabuchi Takahiro , Muto Hirotaka 
Published: November 2021

Inorganic fillers and additives are commonly used as polymer insulating materials such as an epoxy resin (EP) to enhance the thermal, mechanical, and, in some cases, electrical characteristics. The electrical treeing breakdown test is conducted to investigate the filler addition effect on EP's electrical features containing titanium oxide with nano‐size (nTiO2) and the submicron—a few micros‐sized aggregates of nTiO2. EP with a nTiO2 content of 1 vol% has about a 60% higher treeing breakdown voltage under an AC ramp voltage application and a longer insulation lifetime under a constant AC voltage application than those of EP. Furthermore, the treeing breakdown tests in the multi‐insulation configuration adapted to the practical rotating machine were performed. The enhancement effect caused by adding the nTiO2 is also confirmed in the multi‐insulation configuration containing the mica sheet and the EP/nTiO2 nanocomposite. The nTiO2 filler may capture an electron, leading to the generation and growth of an electron avalanche. The submicron—a few micron‐sized aggregates of nTiO2 may also improve the treeing property by the field relaxation effects caused by many tree branching, and the increasing impact of the effective distance between electrodes due to the nTiO2 aggregates as well as the electron capture effect and the barrier effect on the tree channel by filling nTiO2. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Nutritional consulting in regular veterinary practices in Belgium and the Netherlands
Authors: Blees Niels R. , Vandendriessche Veerle L. , Corbee Ronald J. , Picavet Philippe , Hesta Myriam 
Published: November 2021

AbstractBackgroundIncreased interest in nutrition by dog and cat owners stresses the importance of providing tailored nutritional guidance for each patient by veterinarians. The World Small Animal Veterinary Association (WSAVA) has provided guidelines to help veterinarians implement this in every‐day patient care, by screening patients for the presence of nutritional risk factors, establishing tailored nutritional plans and providing adequate patient follow‐up tools.ObjectivesThis study aimed to assess the use of nutritional assessments in companion animal practices, and to investigate differences between Dutch and Belgian veterinarians.MethodsA survey was conducted among Dutch and Belgian veterinarians. Of the 423 respondents, 53% were from Belgium, and 47% were from the Netherlands.ResultsOnly 21% had prior knowledge of the WSAVA nutritional assessment guidelines. General trends in the usage of nutritional assessments were similar in the examined countries. Aside from weighing, diet evaluation by collecting dietary information and body condition or muscle condition scoring were used infrequently, mostly due to insufficient knowledge of the methods. Nutritional recommendations were often made as part of a treatment plan, and were mostly made by veterinarians, but in Dutch practices also by veterinary nurses.ConclusionDespite the fact that nutritional recommendations are a regular part of treatment plans, nutritional risk factors may be missed due to a lack of completely performed nutritional assessments. It remains important to promote the benefits of regular nutritional assessments to veterinarians, which will improve patients’ health.
A Carefare Regime
Authors: Fodor Eva 
Published: November 2021

AbstractHungary’s anti-liberal government has invented a novel solution to the care crisis, which I call a “carefare regime”. This chapter describes four key features of the policies, policy practice and discourse that make up Hungary’s carefare regime. I argue that in contrast to welfare state models familiar from developed democracies, in post-2010 Hungary, women’s claims to social citizenship are most successfully made on the basis of doing care work. The state is re-engineered rather retrenched: services are not commodified but “churchified” in an effort to redistribute resources and build political loyalty. Women are constructed as “naturally” responsible for reproduction and care and this responsibility is tied to sentimentalized notions about femininity and true womanhood. In addition to providing care in the household, women are increasingly engaged in the paid labor market too, where the tolerance for gender inequality is officially mandated. A carefare regime provides limited financial advantages for a select group of women, while simultaneously increasing their devalued work burden both in and outside the household: it feeds a growing underclass of women workers.
Fostering in a Carefare Regime
Authors: Fodor Eva 
Published: November 2021

AbstractThis chapter is about foster parents and their work. Recent changes in the regulation of foster care illustrate the formation and operation of a carefare regime: the transformation of state policies and services and the integration of foster parents into the “deserving” female working and caring underclass. Relying on two years of participant observations and interviews with foster parents, experts, guardians, social workers and foster parent agency personnel, I describe the highly skilled care work most foster parents provide in demanding circumstances for a practically endless number of work hours. I explain how their status has been transformed from being volunteers to being contracted employees who work in increasingly precarious circumstances for extremely low wages. I argue that sentimentalization of care work is used by policy makers to discipline foster mothers into accepting the new terms of their relationship and by foster parents too to rationalize their compliance.
Armut und soziale Netzwerke: Empirische Befunde
Authors: Knabe André 
Published: November 2021

ZusammenfassungDie ersten beiden Abschnitte des Literaturteils beschäftigen sich mit den Wechselwirkungen zwischen Armut und sozialen Beziehungsnetzwerken. Armut beeinflusst soziale Netzwerke hinsichtlich ihrer Größe, ihrer Zusammensetzung und der Qualität der Beziehungen, also des Umfangs der Ressourcen, die sich aus Netzwerken ziehen lassen (3.1). In der entgegengesetzten Richtung werden Mechanismen des sozialen Drucks (z. B. in Peergruppen) sowie ressourcenintensiver Anstrengungen der Anpassung an statushöhere Gruppen (Armut verbergen, versuchen, „oben“ mitzuhalten) diskutiert, die dazu führen können, dass sich die Armutssituation reproduziert oder sogar verschärft (3.2). Im dritten Abschnitt werden Typologien betrachtet, die diese Zusammenhänge innerhalb der Gruppe der Armen differenziert betrachten (3.3). Schließlich werden die Ergebnisse des Literaturstudiums in einem zusammenfassenden Abschnitt reflektiert, um daraus Überlegungen und Fragestellungen im Hinblick auf die eigene empirische Untersuchung abzuleiten (3.4).
Ein Mixed-Methods-Design zur Erforschung »sozialer« Armut
Authors: Knabe André 
Published: November 2021

ZusammenfassungIn diesem Kapitel werden die Datengrundlage, die Befragungsinstrumente und die Vorgehensweise bei der Datenerhebung vorgestellt, um darauf aufbauend die Schritte der Auswertung der so gewonnenen Daten zu beschreiben. Em Ende steht eine Reflexion zum Verhältnis von standardisiert erhobenen Netzwerkdaten zu qualitativem Interviewmaterial und zu den Möglichkeiten und Grenzen der Integration dieser beiden Ansätze.
»Soziale« Armut aus struktureller und subjektiver Perspektive
Authors: Knabe André 
Published: November 2021

ZusammenfassungDie Analyse der standardisierten Netzwerkdaten und der problemzentrierten Interviews erfolgt in drei Schritten. Zunächst werden die Strukturen der sozialen Beziehungsnetzwerke der Befragten unter Anwendung statistischer Verfahren analysiert. Dazu werden Netzwerkmaße berechnet, und einer explorativen Faktorenanalyse unterzogen, mithilfe derer Dimensionen zur Unterscheidung der Netzwerke im Sample identifiziert werden. Die quantitative Typisierung der Netzwerke erfolgt im Rahmen einer Clusteranalyse, aus der drei voneinander zu unterscheidende Netzwerktypen hervorgehen.Im zweiten Schritt werden die subjektive Wahrnehmung und das Bewältigungshandeln der Befragten analysiert. Im Zentrum dieser Analyse stehen ihre alltäglichen Handlungsstrategien unter der Bedingung materieller Knappheit und Statusunsicherheit. Es wird analysiert, inwiefern es den Befragten gelingt, ausgehend von ihrer sozio-strukturellen Einbettung ein Leben im Einklang mit ihren persönlichen und kollektiven Idealen, Interessen und Verbindlichkeiten zu führen (→ Agency nach Emirbayer und Goodwin – siehe Abschnitt 2.3.2). Besondere Aufmerksamkeit wird dabei auf die Bewältigungschancen und -hindernisse gerichtet, die aus der Einbettung in soziale Beziehungen resultieren. Auch die Ergebnisse dieser Analyse werden in einer Typologie festgehalten.Schließlich erfolgt im dritten Schritt die Zusammenführung der qualitativen mit der quantitativen Analyse. Es wird gezeigt, welche Wechselwirkungen zwischen der Einbettung in quantitativ identifizierbare Gelegenheitsstrukturen und der subjektiven Wahrnehmung der Befragten bestehen und welche Bewältigungschancen sich daraus ergeben.﻿
Digital souveräne Gestaltung von Services – ein marktfähiger Mehrwert?
Authors: Lehmann Claudia , Dörr Luca 
Published: November 2021

ZusammenfassungViele kleine und mittelständische Unternehmen (KMU) befinden sich in einem Transformationsprozess, der die von ihnen angebotenen Dienstleistungen und Produkte genauso verändert wie ihre Geschäftsprozesse und Organisationsstrukturen. Die Wertschöpfung einzelner Unternehmen verändert sich zur Wert Co-Creation innerhalb eines Produktionsnetzwerkes. Hierbei spielt die Generierung sowie der Austausch von Daten über den gesamten Produktlebenszyklus eine Schlüsselrolle. Diese ermöglichen die Zusammenarbeit, um mittels Datenanalysen geeignete Dienstleistungen für Endkunden anzubieten. Zur Realisierung einer umfassenden digitalen Wertschöpfungskette ist ein Umdenken von Unternehmen und deren Mitarbeitenden in vernetzten Dienstleistungssystemen notwendig. Dies ist in vielen Fällen nicht so einfach umsetzbar, da Dienstleistungssysteme und deren Entwicklung durch eine hohe Komplexität gekennzeichnet sind. Der nachstehende Artikel zeigt auf, welchen Herausforderungen und Chancen KMU im Transformationsprozess gegenüberstehen und wie insbesondere der Einbezug der Aspekte digitaler Souveränität dazu beitragen kann, verschiedenste Stakeholder und Ressourcen kollaborativ auf ein gemeinsames Wertversprechen zu bündeln und nutzerzentrierte Dienstleistungssysteme zu entwickeln. Souveränität wird in diesem Kontext als die Eigenschaft verstanden, sich selbstständig über relevante Technologien sowie neue technische Möglichkeiten zu informieren, um darauf aufbauend zwischen mehreren Optionen das passende und nutzenstiftenden Angebot auszuwählen, sodass die Fragen „Was bedeutet Digitalisierung für mein Unternehmen und wie setze ich den strategischen Kurs?“ beantwortet werden können.
Regulierung und Zertifizierung von KI in der Industrie: Ziele, Kriterien und Herausforderungen
Authors: Mangelsdorf Axel , Wittenbrink Nicole , Gabriel Peter 
Published: November 2021

ZusammenfassungMit dem Vorschlag der Europäischen Kommission zur Regulierung von Künstlicher Intelligenz (dem Artificial Intelligence Act) ist die Zertifizierung von KI-Systemen in den Fokus gerückt. Gleichzeitig werden mit der Veröffentlichung der ersten Prüfkriterien die Anforderungen der Zertifizierung für Unternehmen konkreter. Der vorliegende Beitrag stellt den Regulierungsvorschlag der Kommission vor und fasst die dazugehörige Fachdebatte zusammen. Danach werden die Anforderungen eines Prüfkatalog zur Zertifizierung von KI-Systemen anhand eines ersten Vorschlags aus dem Projekt „Zertifizierte KI“ präsentiert und bewertet.
On the double copy for spinning matter
Authors: Bautista Yilber Fabian , Guevara Alfredo 
Published: November 2021

Abstract
We explore various tree-level double copy constructions for amplitudes including massive particles with spin. By working in general dimensions, we use that particles with spins s ≤ 2 are fundamental to argue that the corresponding double copy relations partially follow from compactification of their massless counterparts. This massless origin fixes the coupling of gluons, dilatons and axions to matter in a characteristic way (for instance fixing the gyromagnetic ratio), whereas the graviton couples universally reflecting the equivalence principle. For spin-1 matter we conjecture all-order Lagrangians reproducing the interactions with up to two massive lines and we test them in a classical setup, where the massive lines represent spinning compact objects such as black holes. We also test the amplitudes via CHY formulae for both bosonic and fermionic integrands. At five points, we show that by applying generalized gauge transformations one can obtain a smooth transition from quantum to classical BCJ double copy relations for radiation, thereby providing a QFT derivation for the latter. As an application, we show how the theory arising in the classical double copy of Goldberger and Ridgway can be naturally identified with a certain compactification of $$ \mathcal{N} $$
N
= 4 Supergravity.