bluuebunny/crossref_metadata_2025_split huggingface dataset:
The manifold role of octapeptide repeats in prion protein assembly
Authors: Guadagno Amy H. , Medina Scott H. 
Published: January 2023

AbstractPrion protein misfolding is associated with fatal neurodegenerative disorders such as kuru, Creutzfeldt–Jakob disease, and several animal encephalopathies. While the C‐terminal 106–126 peptide has been well studied for its role in prion replication and toxicity, the octapeptide repeat (OPR) sequence found within the N‐terminal domain has been relatively under explored. Recent findings that the OPR has both local and long‐range effects on prion protein folding and assembly, as well as its ability to bind and regulate transition metal homeostasis, highlights the important role this understudied region may have in prion pathologies. This review attempts to collate this knowledge to advance a deeper understanding on the varied physiologic and pathologic roles the prion OPR plays, and connect these findings to potential therapeutic modalities focused on OPR‐metal binding. Continued study of the OPR will not only elucidate a more complete mechanistic model of prion pathology, but may enhance knowledge on other neurodegenerative processes underlying Alzheimer's, Parkinson's, and Huntington's diseases.
Mutational scan inferred binding energetics and structure in intrinsically disordered protein CcdA
Authors: Chandra Soumyanetra , Manjunath Kavyashree , Asok Aparna , Varadarajan Raghavan 
Published: January 2023

AbstractUnlike globular proteins, mutational effects on the function of Intrinsically Disordered Proteins (IDPs) are not well‐studied. Deep Mutational Scanning of a yeast surface displayed mutant library yields insights into sequence‐function relationships in the CcdA IDP. The approach enables facile prediction of interface residues and local structural signatures of the bound conformation. In contrast to previous titration‐based approaches which use a number of ligand concentrations, we show that use of a single rationally chosen ligand concentration can provide quantitative estimates of relative binding constants for large numbers of protein variants. This is because the extended interface of IDP ensures that energetic effects of point mutations are spread over a much smaller range than for globular proteins. Our data also provides insights into the much‐debated role of helicity and disorder in partner binding of IDPs. Based on this exhaustive mutational sensitivity dataset, a rudimentary model was developed in an attempt to predict mutational effects on binding affinity of IDPs that form alpha‐helical structures upon binding.
Quantitative systems pharmacology model of GITR‐mediated T cell dynamics in tumor microenvironment
Authors: Ji Yan , Madrasi Kumpal , Knee Deborah A. , Gruenbaum Lore , Apgar Joshua F. , Burke John M. , Gomes Bruce 
Published: January 2023

AbstractT cell interaction in the tumor microenvironment is a key component of immuno‐oncology therapy. Glucocorticoid‐induced tumor necrosis factor receptor (TNFR)‐related protein (GITR) is expressed on immune cells including regulatory T cells (Tregs) and effector T cells (Teffs). Preclinical data suggest that agonism of GITR in combination with Fc‐γ receptor‐mediated depletion of Tregs results in increased intratumoral Teff:Treg ratio and tumor shrinkage. A novel quantitative systems pharmacology (QSP) model was developed for the murine anti‐GITR agonist antibody, DTA‐1.mIgG2a, to describe the kinetics of intratumoral Tregs and Teffs in Colon26 and A20 syngeneic mouse tumor models. It adequately captured the time profiles of intratumoral Treg and Teff and serum DTA‐1.mIgG2a and soluble GITR concentrations in both mouse models, and described the response differences between the two models. The QSP model provides a quantitative understanding of the trade‐off between maximizing Treg depletion versus Teff agonism, and offers insights to optimize drug design and dose regimen.
Maneuvering the odds: The dynamics of venture capital decision‐making
Authors: Petty Jeffrey S. , Gruber Marc , Harhoff Dietmar 
Published: January 2023

AbstractResearch SummaryThis article investigates venture capital (VC) decision‐making, a process that occurs under changing conditions and limited, ambiguous information. We shed new light on the inherent dynamics of this strategic process. One of the key distinguishing features of our study is its unprecedented access to the internal decision‐making process of a VC firm. By analyzing unique, longitudinal data capturing 2,383 proposal selection processes conducted over the life of one venture capital fund, we show how decision‐making speed and the information cues that decision makers rely upon will, over time, change in systematic and predictable ways. Specifically, our approach allows us to identify fundamental, unexplored patterns with respect to the selection process as a whole and the multiple stages within the process.Managerial SummaryEach year venture capitalists receive hundreds of investment proposals, but is every proposal received by a venture capitalist processed equally? In this study, we show how the source of a proposal and the available amount of investment capital, factors that are not contained within the pages of a proposal, may influence the investment decision‐making process. Our results highlight the impact of being referred to a venture capitalist by a trusted source, as more time is spent evaluating these proposals and they proceed further along in the process. We also find that venture capitalists process proposals more quickly as the capital in the fund is invested over the life of the fund.
Code smell prioritization in object‐oriented software systems: A systematic literature review
Authors: Verma Renu , Kumar Kuldeep , Verma Harsh K. 
Published: January 2023

AbstractCode smells indicate poor design and imperfection in coding style. They increase maintenance costs and degrade software quality. Detecting and mitigating these code smells reduce the effects of flaws present in the software design. However, to save time and effort, it is a good practice to prioritize critical code smells and resolve them first. There have been various empirical studies on code smell prioritization in the last decades. Although the research community has been continuously working on the prioritization of code smells, yet a systematic mapping of all these studies would provide a panorama of research work. With this motivation, we selected 39 primary studies published between May 2011 and May 2022 and classified them based on seven factors: (i) code smells, (ii) factors, (iii) evaluation techniques, (iv) tools, (v) ranking formulas, (vi) data sets used, and (vii) measurements used for validating the research work. This paper aims to outline and discuss the prioritization procedure for code smells in object‐oriented software systems. The issues and recommendations for every question act as input for the researchers and industrialists for further research. Some issues for further investigation are less coverage of architecture smells, limited ranking formulas, lack of automated evaluation techniques, and so forth.
Exposure to dipentyl phthalate in utero disrupts the adrenal cortex function of adult male rats by inhibiting SIRT1/PGC‐1α and inducing AMPK phosphorylation
Authors: Chen Haiqiong , Liu Miaoqing , Li Qiyao , Zhou Pingjiang , Huang Jie , Zhu Qiqi , Li Zhongrong , Ge Ren‐shan 
Published: January 2023

AbstractDi‐n‐pentyl phthalate (DPeP) is an endocrine‐disrupting phthalate plasticizer. The objective of this study was to investigate the effect of DPeP on adrenocortical function in adult male rats following in utero exposure. DPeP (0, 10, 50, 100, and 500 mg/kg/day) was administered by gavage to pregnant Sprague–Dawley rats from gestational day 14 to 21. The morphology and function of the adrenal cortex in 56‐day‐old male offspring were studied. DPeP at 100 and 500 mg/kg/day significantly reduced serum aldosterone levels and at 500 mg/kg/day markedly reduced corticosterone and adrenocorticotropic hormone levels. DPeP at 10–500 mg/kg markedly reduced the thickness of zona glomerulosa without affecting the thickness of zona fasciculata. DPeP significantly downregulated the expression of Agtr1a, Mc2r, Scarb1, Cyp11a1, Hsd3b1, Cyp21, Cyp11b1, Cyp11b2, Nr5a1, Nr4a2, and Bcl2 genes as well as their proteins. DPeP at 500 mg/kg/day significantly increased phosphorylated AMPK, while DPeP at 100 mg/kg/day and higher doses reduced phosphorylated AKT1 and total SIRT1 level. DPeP at 100 and 500 μM markedly induced reactive oxygen species and apoptosis in H295R cells after 24 h of culture. In conclusion, in utero exposure to DPeP disrupts adrenocortical function of the adult male offspring by (1) increasing AMPK phosphorylation and decreasing AKT1 phosphorylation and SIRT1 levels, (2) reducing adrenocorticotropic hormone levels, and (3) possibly inducing oxidative stress and apoptosis.
Do prokinetic agents provide symptom relief through acceleration of gastric emptying? An update and revision of the existing evidence
Authors: Goelen Nick , Jones Mike , Huang I‐Hsuan , Carbone Florenca , Janssen Pieter , Tack Jan 
Published: January 2023

AbstractBackgroundGastroparesis and functional dyspepsia are disorders characterized by upper gastrointestinal symptoms and multifaceted etiologies. One of the main therapeutic approaches is accelerating gastric emptying (GE) by means of prokinetic agents. Their efficacy has been demonstrated, although the association between symptom improvement and acceleration of emptying is less clear. Meta‐analyses have found contradictory results. Differences in applied methodology and included trials might drive these contradictions.ObjectiveTo provide a transparent meta‐analysis update to elucidate the association between symptom improvement and acceleration of GE due to gastroprokinetic agents available for long‐term use in patients with gastroparesis.DesignTwo approaches from earlier meta‐analyses were executed and compared. One analyzed the relative changes on active treatment versus baseline, the other compared the change from baseline on active treatment versus the change from baseline on placebo. Papers that reported sufficient numerical data for both analyses were selected. Both analyses included the same trials.ResultsOverall, both approaches yield the same positive direction of association between symptom improvement and acceleration of emptying (0.291 (−0.391, 0.972), p = 0.4 and 0.453 (0.123, 0.782), p = 0.007 for the active‐only and placebo‐controlled analysis respectively). The association between symptom improvement and GE acceleration for studies using optimal GE tests was either 0.028 (p > 0.9) or 0.463 (p = 0.007), and for sub‐optimal GE tests was either 0.370 (p = 0.4) or 0.052 (p > 0.9) depending on the used meta‐analysis methodology.ConclusionsThe applied methodology for GE testing, and the meta‐analysis substantially impacts the conclusion. When considering the clinically relevant outcome of improvement from baseline, symptoms and emptying improve with prokinetics, but no correlation is found between both aspects. When the change over placebo is considered, limiting the analysis to scientifically more rigorous study approaches, changes in emptying rate and symptom improvement are positively associated.
Interleukin‐17 as a spatiotemporal bridge from acute to chronic inflammation: Novel insights from computational modeling
Authors: Shah Ashti M. , Zamora Ruben , Vodovotz Yoram 
Published: January 2023

AbstractA systematic review of several acute inflammatory diseases ranging from sepsis and trauma/hemorrhagic shock to the relevant pathology of the decade, COVID‐19, points to the cytokine interleukin (IL)‐17A as being centrally involved in the propagation of inflammation. We summarize the role of IL‐17A in acute inflammation, leveraging insights made possible by biological network analysis and novel computational methodologies aimed at defining the spatiotemporal spread of inflammation in both experimental animal models and humans. These studies implicate IL‐17A in the cross‐tissue spread of inflammation, a process that appears to be in part regulated through neural mechanisms. Although acute inflammatory diseases are currently considered distinct from chronic inflammatory pathologies, we suggest that chronic inflammation may represent repeated, cyclical episodes of acute inflammation driven by mechanisms involving IL‐17A. Thus, insights from computational modeling of acute inflammatory diseases may improve diagnosis and treatment of chronic inflammation; in turn, therapeutics developed for chronic/autoimmune disease may be of benefit in acute inflammation.This article is categorized under:
Immune System Diseases > Computational Models
Optimal decay rates of a nonconservative compressible two‐phase fluid model
Authors: Wang Huaqiao , Wang Juan , Wu Guochun , Zhang Yinghui 
Published: January 2023

AbstractWe are concerned with the time decay rates of strong solutions to a nonconservative compressible viscous two‐phase fluid model in the whole space . Compared to the previous related works, the main novelty of this paper lies in the fact that it provides a general framework that can be used to extract the optimal decay rates of the solution as well as its all‐order spatial derivatives from one‐order to the highest‐order, which are the same as those of the heat equation. Furthermore, for well‐chosen initial data, we also show the lower bounds on the decay rates. Our methods mainly consist of Hodge decomposition, low‐ and high‐frequency decomposition, delicate spectral analysis, and energy method based on finite induction.
Engagement
Authors: Sheikh Haroon , Prins Corien , Schrijvers Erik 
Published: January 2023

AbstractThe next overarching task we have identified for AI’s integration into society concerns the engagement of stakeholders. This raises the following question: ‘who should be involved?’ When any new technology is introduced, after all, various parties are involved right from the start. The previous chapter on contextualization made this apparent; it showed that both companies and government started working with AI at an early stage. In discussing their involvement then, our focus was the question ‘how do we make AI work’? Companies and government organizations have the resources and impetus needed to become key drivers of AI’s use in society. As a result, they also have a lot of influence over how it is implemented in practice. In this chapter, by contrast, we home in on parties that do not initially use AI themselves but – given its ubiquitous use – are likely to encounter this technology in their activities. Our particular focus is parties in civil society.
Münsteraner Fahrradunfälle im Wandel der Zeit
Authors: Schlautmann Désirée , Raschke Michael , Weiss Udo , Wieskötter Britta , Ueberberg Johanna , Juhra Christian 
Published: January 2023

Zusammenfassung
Hintergrund
Fahrräder sind seit vielen Jahren ein beliebtes Verkehrsmittel. Gerade in Zeiten der verstärkten Klimadiskussion ist das Fahrrad als umweltfreundliches und kostengünstiges Verkehrsmittel weiter in den Fokus gerückt. Die Radwege und Straßen werden immer voller, und neue Verkehrsmittel wie Pedelecs oder E‑Scooter kommen auf.

Methoden
Es wurden insgesamt 4 Studien des Universitätsklinikum Münster zu Fahrradunfällen und die amtliche Unfallstatistik der Polizei Münster miteinander verglichen. Im Zeitraum von 2009 bis 2019 wurden 3 Studien durchgeführt, die alle Fahrradunfälle, und eine Studie, welche nur Pedelecfahrer gesondert berücksichtigt.

Ergebnisse
Die Altersverteilung sowie Hauptunfallursachen sind über die Jahre hinweg nahezu gleich geblieben. Die Anzahl an Pedelecunfällen hat zugenommen. Pedelecfahrer weisen ein höheres Durchschnittsalter und einen höheren Anteil an intensivstationären Aufenthalten auf. Jedoch weist gerade diese Kohorte auch eine hohe Quote an Helmträgern auf. Insgesamt scheint die Bereitschaft zum Tragen eines Helmes gestiegen zu sein.

Schlussfolgerung
Es ist zu bedenken, dass bei zunehmendem Radverkehr die Sicherheitsmaßnahmen entsprechend erhöht werden müssen. Dabei sollte sich die Unfallverhütung auf 3 große Bereiche konzentrieren: Technik, Erziehung, Durchsetzung.
Design, construction and characterisation of a diode-pumped, three-element, 1-GHz Kerr-lens-modelocked Ti:sapphire oscillator
Authors: Ostapenko Hanna , Mitchell Toby , Castro-Marin Pablo , Reid Derryck T. 
Published: January 2023

AbstractWe present a design and construction prescription for a 1-GHz repetition rate Ti:sapphire laser pumped with a single green pump diode and with a resonator comprising as few as three optical elements. In a three-element configuration, the laser produces 111-fs pulses and exhibits self-starting Kerr-lens modelocking at pump powers above 850 mW. At 1.1 W of pump power, the average output of the laser is over 116 mW, and the slope efficiency is measured to be 13%. With the addition of a fourth dispersion-compensating element to optimise the second-order group-delay intracavity dispersion, we have demonstrated a reduction of the pulse durations to 87 fs with an average power of 108 mW.
Prescription opioids and economic hardship in France
Authors: Natali Ilaria , Dewatripont Mathias , Ginsburgh Victor , Goldman Michel , Legros Patrick 
Published: January 2023

AbstractThis paper studies how opioid analgesic sales are empirically related to socioeconomic disparities in France, with a focus on poverty. This analysis is made possible using the OpenHealth database, which provides retail sales data for opioid analgesics available on the French market. We exploit firm-level data for each of the 94 departments in Metropolitan France between 2008 and 2017. We show that increases in the poverty rate are associated with increases in sales: a one percentage point increase in poverty is associated with approximately a 5% increase in mild opioid sales. Our analysis further shows that opioid sales are positively related to the share of middle-aged people and individuals with basic education only, while they are negatively related to population density. The granularity and longitudinal nature of these data allow us to control for a large pool of potential confounding factors. Our results suggest that additional interventions should be more intensively addressed toward the most deprived areas. We conclude that a combination of policies aimed at improving economic prospects and strictly monitoring access to opioid medications would be beneficial for reducing opioid-related harm.
Perceived climate change risk and global green activism among young people
Authors: D’Uggento Angela Maria , Piscitelli Alfonso , Ribecco Nunziata , Scepi Germana 
Published: January 2023

AbstractIn recent years, the increasing number of natural disasters has raised concerns about the sustainability of our planet’s future. As young people comprise the generation that will suffer from the negative effects of climate change, they have become involved in a new climate activism that is also gaining interest in the public debate thanks to the Fridays for Future (FFF) movement. This paper analyses the results of a survey of 1,138 young people in a southern Italian region to explore their perceptions of the extent of environmental problems and their participation in protests of green movements such as the FFF. The statistical analyses perform an ordinal classification tree using an original impurity measure considering both the ordinal nature of the response variable and the heterogeneity of its ordered categories. The results show that respondents are concerned about the threat of climate change and participate in the FFF to claim their right to a healthier planet and encourage people to adopt environmentally friendly practices in their lifestyles. Young people feel they are global citizens, connected through the Internet and social media, and show greater sensitivity to the planet’s environmental problems, so they are willing to take effective action to demand sustainable policies from decision-makers. When planning public policies that will affect future generations, it is important for policymakers to know the demands and opinions of key stakeholders, especially young people, in order to plan the most appropriate measures, such as climate change mitigation.
Reporting reliability, convergent and discriminant validity with structural equation modeling: A review and best-practice recommendations
Authors: Cheung Gordon W. , Cooper-Thomas Helena D. , Lau Rebecca S. , Wang Linda C. 
Published: January 2023

Abstract
Many constructs in management studies, such as perceptions, personalities, attitudes, and behavioral intentions, are not directly observable. Typically, empirical studies measure such constructs using established scales with multiple indicators. When the scales are used in a different population, the items are translated into other languages or revised to adapt to other populations, it is essential for researchers to report the quality of measurement scales before using them to test hypotheses. Researchers commonly report the quality of these measurement scales based on Cronbach’s alpha and confirmatory factor analysis results. However, these results are usually inadequate and sometimes inappropriate. Moreover, researchers rarely consider sampling errors for these psychometric quality measures. In this best practice paper, we first critically review the most frequently-used approaches in empirical studies to evaluate the quality of measurement scales when using structural equation modeling. Next, we recommend best practices in assessing reliability, convergent and discriminant validity based on multiple criteria and taking sampling errors into consideration. Then, we illustrate with numerical examples the application of a specifically-developed R package, measureQ, that provides a one-stop solution for implementing the recommended best practices and a template for reporting the results. measureQ is easy to implement, even for those new to R. Our overall aim is to provide a best-practice reference for future authors, reviewers, and editors in reporting and reviewing the quality of measurement scales in empirical management studies.
Dynamical low-rank integrators for second-order matrix differential equations
Authors: Hochbruck Marlis , Neher Markus , Schrammer Stefan 
Published: January 2023

AbstractIn this paper, we construct and analyze a new dynamical low-rank integrator for second-order matrix differential equations. The method is based on a combination of the projector-splitting integrator introduced in Lubich and Oseledets (BIT 54(1):171–188, 2014. https://doi.org/10.1007/s10543-013-0454-0) and a Strang splitting. We also present a variant of the new integrator which is tailored to semilinear second-order problems.