bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developments in the synthesis of allylsilanes by transition metal–catalyzed silylation of 1,3-dienes with disilanes
Authors: Katayama Nobuki , Obora Yasushi 
Published: July 2024

Abstract
This highlight review overviews developments in the synthesis of allylsilanes by transition metal–catalyzed silylation of 1,3-dienes with disilanes. We specifically review disilylation, which installs 2 silicon atoms, and silyl-functionalization, which installs both silicon and another atom using disilanes and reagents such as nucleophiles and electrophiles. Utilizing these methods for the silylation of 1,3-dienes provides a robust protocol for the efficient synthesis of the desired allylsilanes in 1 step, thereby streamlining the silyl-functionalization of 1,3-dienes.
Beneficial normalization of cardiac repolarization by carnitine in transgenic short QT syndrome type 1 rabbit models
Authors: Bodi Ilona , Mettke Lea , Michaelides Konstantin , Hornyik Tibor , Meier Stefan , Nimani Saranda , Perez-Feliz Stefanie , El-Battrawy Ibrahim , Bugger Heiko , Zehender Manfred , Brunner Michael , Heijman Jordi , Odening Katja E 
Published: July 2024

Abstract

Aims
Short QT syndrome type 1 (SQT1) is a genetic channelopathy caused by gain-of-function variants in human-ether-a-go-go (HERG) underlying the rapid delayed-rectifier K+ current (IKr), leading to QT-shortening, ventricular arrhythmias, and sudden cardiac death. Data on efficient pharmacotherapy for SQT1 are scarce. In patients with primary carnitine-deficiency, acquired-short QT syndrome (SQTS) has been observed and rescued by carnitine supplementation. Here, we assessed whether carnitine exerts direct beneficial (prolonging) effects on cardiac repolarization in genetic SQTS.

Methods and results
Adult wild-type (WT) and transgenic SQT1 rabbits (HERG-N588K, gain of IKr) were used. In vivo electrocardiograms (ECGs), ex vivo monophasic action potentials (APs) in Langendorff-perfused hearts, and cellular ventricular APs and ion currents were assessed at baseline and during L-Carnitine/C16-Carnitine-perfusion. Two-dimensional computer simulations were performed to assess re-entry-based ventricular tachycardia-inducibility. L-Carnitine/C16-Carnitine prolonged QT-intervals in WT and SQT1, leading to QT-normalization in SQT1. Similarly, monophasic and cellular AP duration (APD) was prolonged by L-Carnitine/C16-Carnitine in WT and SQT1. As underlying mechanisms, we identified acute effects on the main repolarizing ion currents: IKr-steady, which is pathologically increased in SQT1, was reduced by L-Carnitine/C16-Carnitine and deactivation kinetics were accelerated. Moreover, L-Carnitine/C16-Carnitine decreased IKs-steady and IK1. In silico modelling identified IKr changes as the main factor for L-Carnitine/C16-Carnitine-induced APD-prolongation. 2D simulations revealed increased sustained re-entry-based arrhythmia formation in SQT1 compared to WT, which was decreased to the WT-level when adding carnitine-induced ion current changes.

Conclusion
L-Carnitine/C16-Carnitine prolong/normalize QT and whole-heart/cellular APD in SQT1 rabbits. These beneficial effects are mediated by acute effects on IKr. L-Carnitine may serve as a potential future QT-normalizing, anti-arrhythmic therapy in SQT1.
A general and efficient representation of ancestral recombination graphs
Authors: Wong Yan , Ignatieva Anastasia , Koskela Jere , Gorjanc Gregor , Wohns Anthony W , Kelleher Jerome 
Published: July 2024

Abstract
As a result of recombination, adjacent nucleotides can have different paths of genetic inheritance and therefore the genealogical trees for a sample of DNA sequences vary along the genome. The structure capturing the details of these intricately interwoven paths of inheritance is referred to as an ancestral recombination graph (ARG). Classical formalisms have focused on mapping coalescence and recombination events to the nodes in an ARG. However, this approach is out of step with some modern developments, which do not represent genetic inheritance in terms of these events or explicitly infer them. We present a simple formalism that defines an ARG in terms of specific genomes and their intervals of genetic inheritance, and show how it generalizes these classical treatments and encompasses the outputs of recent methods. We discuss nuances arising from this more general structure, and argue that it forms an appropriate basis for a software standard in this rapidly growing field.
Changes in Household Wealth Over the Process of Widowhood Across European Countries
Authors: Kapelle Nicole , Van Winkle Zachary 
Published: July 2024

Abstract

Objectives
Widowhood has been shown to decrease surviving spouses’ economic well-being. However, previous research has focused mostly on income-related outcomes, and has been less attentive to the importance of wealth, the processual nature of spousal death, and cross-national variation. In this study, we assessed how total, housing, and nonhousing wealth changes over the process of widowhood across 11 European countries.

Methods
Individual fixed-effects regressions and longitudinal data from the Survey of Health, Ageing and Retirement in Europe were used to estimate how household net total wealth, housing wealth, and nonhousing wealth changed 3 years prior and 6 or more years after spousal death relative to 4 or more years prior to widowhood in 11 European countries.

Results
In all countries, household net wealth stayed relatively constant across the widowhood process, except for Austria, the Czech Republic, and Poland, where wealth declines were observed especially in the years following death. However, we found declines in housing wealth over the widowhood process, including prior to spousal death, across most countries in our sample, particularly in Austria, France, Denmark, the Czech Republic, and Poland. Declines in housing wealth were generally not reflected by changes in nonhousing wealth but coincided with leaving homeownership and downsizing.

Discussion
Widowhood is associated with lower wealth, especially housing wealth, even in the years before spousal loss. Future research should focus on adjudicating the mechanisms behind country differences and exploring the implications of lost wealth following widowhood for surviving spouses’ well-being and intergenerational transfers.
Pharmacogenomic Assessment of Genes Implicated in Thiopurine Metabolism and Toxicity in a UK Cohort of Pediatric Patients With Inflammatory Bowel Disease
Authors: Coelho Tracy , Cheng Guo , Lewis Sophie , Ashton James J , Barakat Farah , Driscoll Kouros C T , Sholeye-Bolaji Adebola E , Batra Akshay , Afzal Nadeem A , Beattie Robert M , Ennis Sarah 
Published: July 2024

Abstract

Background
Thiopurine drugs are effective treatment options in inflammatory bowel disease and other conditions but discontinued in some patients due to toxicity.

Methods
We investigated thiopurine-induced toxicity in a pediatric inflammatory bowel disease cohort by utilizing exome sequencing data across a panel of 46 genes, including TPMT and NUDT15.

Results
The cohort included 487 patients with a median age of 13.1 years. Of the 396 patients exposed to thiopurines, myelosuppression was observed in 11%, gastroenterological intolerance in 11%, hepatotoxicity in 4.5%, pancreatitis in 1.8%, and “other” adverse effects in 2.8%. TPMT (thiopurine S-methyltransferase) enzyme activity was normal in 87.4%, intermediate 12.3%, and deficient in 0.2%; 26% of patients with intermediate activity developed toxicity to thiopurines. Routinely genotyped TPMT alleles associated with defective enzyme activity were identified in 28 (7%) patients: TPMT*3A in 4.5%, *3B in 1%, and *3C in 1.5%. Of these, only 6 (21%) patients developed toxic responses. Three rare TPMT alleles (*3D, *39, and *40) not assessed on routine genotyping were identified in 3 patients, who all developed toxic responses. The missense variant p.R139C (NUDT15*3 allele) was identified in 4 patients (azathioprine 1.6 mg/kg/d), but only 1 developed toxicity. One patient with an in-frame deletion variant p.G13del in NUDT15 developed myelosuppression at low doses. Per-gene deleteriousness score GenePy identified a significant association for toxicity in the AOX1 and DHFR genes.

Conclusions
A significant association for toxicity was observed in the AOX1 and DHFR genes in individuals negative for the TPMT and NUDT15 variants. Patients harboring the NUDT15*3 allele, which is associated with myelosuppression, did not show an increased risk of toxicity.
Evolution in fossil time series reconciles observations in micro- and macroevolution
Authors: Voje Kjetil Lysne , Saito-Kato Megumi , Spanbauer Trisha L 
Published: July 2024

Abstract
Extrapolating microevolutionary models does not always provide satisfactory explanations for phenotypic diversification on million-year time scales. For example, short-term evolutionary change is often modelled assuming a fixed adaptive landscape, but macroevolutionary changes are likely to involve changes in the adaptive landscape itself. A better understanding of how the adaptive landscape changes across different time intervals and how these changes cause populations to evolve has the potential to narrow the gap between micro- and macroevolution. Here, we analyze two fossil diatom time series of exceptional quality and resolution covering time intervals of a few hundred thousand years using models that account for different behaviours of the adaptive landscape. We find that one of the lineages evolves on a randomly and continuously changing landscape, whereas the other lineage evolves on a landscape that shows a rapid shift in the position of the adaptive peak of a magnitude that is typically associated with species-level differentiation. This suggests phenotypic evolution beyond generational timescales may be a consequence of both gradual and sudden repositioning of adaptive peaks. Both lineages show rapid and erratic evolutionary change and are constantly readapting towards the optimal trait state, observations that align with evolutionary dynamics commonly observed in contemporary populations. The inferred trait evolution over a span of a few hundred thousand years in these two lineages is, therefore, chimeric in the sense that it combines components of trait evolution typically observed on both short and long timescales.
Differential phenological responses to temperature among various stages of spring vegetation green-up
Authors: Jiang Nan , Shen Miaogen , Yang Zhiyong 
Published: July 2024

Abstract
Vegetation green-up is occurring earlier due to climate warming across the Northern Hemisphere, with substantial influences on ecosystems. However, it is unclear whether temperature responses differ among various green-up stages. Using high-temporal-resolution satellite data of vegetation greenness and averaging over northern vegetation (30–75° N), we found the negative interannual partial correlation between the middle green-up stage timing (50% greenness increase in spring–summer) and temperature (RP = −0.73) was stronger than those for the onset (15% increase, RP = −0.65) and end (90% increase, RP = −0.52) of green-up during 2000–2022. Spatially, at high latitudes, the middle green-up stage showed stronger temperature responses than the onset, associated with greater low-temperature constraints and stronger control of snowmelt on green-up onset as well as greater spring frost risk. At middle latitudes, correlations with temperature were similar between the onset and middle stages of green-up, except for grasslands of the Mongolian Plateau and interior western USA, where correlations with temperature were weaker for the middle stage due to water limitation. In contrast, the end of the green-up showed weaker temperature responses than the middle due to insufficient water and high climatic temperature during the end of the green-up in most of the study region, except for cold regions in the interior western USA, western Russia and the Tibetan Plateau, where temperature was still a main driver during end of green-up. Our findings underscore the differences in temperature responses among green-up stages, which alters the temporal alignment between plants and environmental resources.
Spatio-temporal forecasting for the US Drought Monitor
Authors: Erhardt Robert , Hepler Staci , Wolodkin Daniel , Greene Andy 
Published: July 2024

Abstract
The US Drought Monitor is the leading drought monitoring tool in the United States. Updated weekly and freely distributed, it records the drought conditions as geo-referenced polygons showing one of six ordered levels. These levels are determined by a mixture of quantitative environmental measurements and local expert opinion across the entire United States. At present, forecasts of the Drought Monitor only convey the expected direction of drought development (i.e. worsen, persist, subside) and do not communicate any uncertainty. This limits the utility of forecasts. In this paper, we describe a Bayesian spatio-temporal ordinal hierarchical model for use in modelling and projecting drought conditions. The model is flexible, scalable, and interpretable. By viewing drought data as areal rather than point-referenced, we reduce the cost of sampling from the posterior by avoiding dense matrix inversion. Draws from the posterior predictive distribution produce future forecasts of actual drought levels—rather than only the direction of drought development—and all sources of uncertainty are propagated into the posterior. Spatial random effects and an autoregressive model structure capture spatial and temporal dependence, and help ensure smoothness in forecasts over space and time. The result is a framework for modelling and forecasting drought levels and capturing forecast uncertainty.
‘Europe was a dream for me. This dream came true but remains unfulfilled at the same time’: Navigating life aspirations among forced migrants in Austria and Italy
Authors: Siviş Selin , Brändle Verena K , Eberl Jakob-Moritz , Wyatt Sophia , Braun Kathrin , Metwally Iman , Boomgaarden Hajo 
Published: July 2024

Abstract
In this article, we analyse the interplay between forced migrants’ retrospective expectations and their current experiences in the host country, and how this interaction informs their aspirations in relation to their potential life trajectories. By zooming in on the Austrian and Italian cases derived from qualitative data, this article investigates forced migrants’ retrospective perspectives on the ‘good life’ in (imagined) Europe and their experienced-informed perspectives of the host country context—reception policies—after migration by tracing individuals’ self-reported perceptions of life aspirations over the course of their migration journey. By applying the aspirations-capability framework, our analysis traces what ‘happens’ after people have submitted their asylum applications. In this way, this research sheds light on the process of adapting to a new context with gravely restricted capabilities and how this affects people’s life aspirations. By doing so, we demonstrate that aspirations are not only dynamic and flexible, but capabilities also change due to the structural confines of national asylum procedures. This study therefore brings an innovative perspective to study life aspirations and capabilities by showing the importance of reflecting not only aspirations but also the (in)capability of acting in the present which informs the process of revisiting original life aspirations for individuals seeking asylum. This process begins after the arrival, based on changes in their capabilities, specifically the national asylum structures that confine them.
Chemical and engineering bases for green H2O2 production and related oxidation and ammoximation of olefins and analogues
Authors: Qiao Minghua , Zhou Xinggui , Du Zexue , Wu Peng , Zong Baoning 
Published: July 2024

ABSTRACT
Plastics, fibers and rubber are three mainstream synthetic materials that are essential to our daily lives and contribute significantly to the quality of our lives. The production of the monomers of these synthetic polymers usually involves oxidation or ammoximation reactions of olefins and analogues. However, the utilization of C, O and N atoms in current industrial processes is &lt;80%, which represents the most environmentally polluting processes for the production of basic chemicals. Through innovation and integration of catalytic materials, new reaction pathways, and reaction engineering, the Research Institute of Petroleum Processing, Sinopec Co., Ltd. (RIPP) and its collaborators have developed unique H2O2-centered oxidation/ammoximation technologies for olefins and analogues, which has resulted in a ¥500 billion emerging industry and driven trillions of ¥s' worth of downstream industries. The chemical and engineering bases of the production technologies mainly involve the integration of slurry-bed reactors and microsphere catalysts to enhance H2O2 production, H2O2 propylene/chloropropylene epoxidation for the production of propylene oxide/epichlorohydrin, and integration of H2O2 cyclohexanone ammoximation and membrane separation to innovate the caprolactam production process. This review briefly summarizes the whole process from the acquisition of scientific knowledge to the formation of an industrial production technology by RIPP. Moreover, the scientific frontiers of H2O2 production and related oxidation/ammoximation processes of olefins and analogues are reviewed, and new technological growth points are envisaged, with the aim of maintaining China's standing as a leader in the development of the science and technologies of H2O2 production and utilization.
Limited waterpower contributed to rise of steam power in British “Cottonopolis”
Authors: Jonell Tara N , Jones Peter , Lucas Adam , Naylor Simon 
Published: July 2024

Abstract
The Industrial Revolution precipitated a pivotal shift from waterpower to coal-fueled steam power in British textile mills. Although it is now widely accepted that steam was chosen to power factories despite the availability of sufficient waterpower resources across most of Britain, the location and suitability of that waterpower during the early 19th century remain underexplored. Here, we employ quantitative fluvial geomorphology alongside historical climate data, factory records, and a catalog of over 26,000 mill sites to reveal that waterpower was abundant for most of early 19th century Britain, except in the central hub of British cotton production: Greater Manchester in the Mersey Basin. Our findings show that surging factory mechanization and overcrowding on key waterways in the Mersey Basin compounded waterpower scarcity arising from a drier 19th century climate. Widespread adoption of coal-fueled steam engines in certain key industrial centers of Britain was a strategy aimed at ameliorating some of the reduced reliability of waterpower. The fact that steam engines were frequently used in water-powered factories in many industrial regions until the third quarter of the 19th century to recirculate water to provide that power, or as a power supplement when waterpower availability was restricted, adds further weight to our argument. Rapid adoption of coal-powered steam engines reshaped the social and structural landscape of industrial work, firmly established Britain's prominence as an industrial powerhouse, and had lasting global industrial and environmental impacts.
Evoked questions and inquiring attitudes
Authors: Willard-Kyle Christopher , Millson Jared , Whitcomb Dennis 
Published: July 2024

Abstract
Drawing inspiration from the notion of evocation employed in inferential erotetic logic, we defend an ‘evoked questions norm’ on inquiring attitudes. According to this norm, it is rational to have an inquiring attitude concerning a question only if that question is evoked by your background information. We offer two arguments for this norm. First, we develop an argument from convergence. Insights from several independent literatures (20th-century ordinary-language philosophy, inferential erotetic logic, inquisitive epistemic logic, and contemporary zetetic epistemology), all converge on the evoked questions norm. Second, we show that suitably interpreted, the evoked questions norm correctly predicts several underappreciated kinds of bad questions. It does this, in part, by recovering versions of previously defended ignorance and knowledge norms. Some of those bad questions cannot be predicted by either norm singly, but only when corporately taken to reflect a common normative category. We identify this category as evocation.
Constraining Spacetime Dimensions in Quantum Gravity by Scale Invariance and Electric–Magnetic Duality
Authors: Morita Takeshi 
Published: July 2024

Abstract
We consider a low-energy effective theory of p-branequaes in a D-dimensional spacetime, and impose two conditions: (1) the theory is scale-invariant, and (2) the electric–magnetic dual $(D-p-4)$-branes exist and they obey the same type of interactions to the p-branes. (We also assume other natural conditions such as Lorentz invariance but not string theory, supersymmetry, supergravity, and so on.) We then ask what values of p and D are consistent with these conditions. Using simple dimensional analysis, we find that only two solutions are possible: $(p,D)=(2,11)$ and $(p,D)=(2n-1,4n+2)$, ($n=1,2,3,\cdots$). The first solution corresponds to M-theory, and the second solutions at $n=1$ and $n=2$ correspond to self-dual strings in little string theory and D3-branes in type IIB superstring theory, respectively, while the second solutions for $n \ge 3$ are unknown but would be higher spin theories. Thus, quantum gravity (massless spin two theory) satisfying our two conditions would only be superstring theories, and the conditions would be strong enough to characterize superstring theories in quantum gravity.
Dissolvable microneedles loaded ginsenoside Rg3 liposome: a transdermal delivery approach for alopecia treatment
Authors: Yang Qin , Guo Peng , Lei Pengkun , Yang Qiaolin , Liu Yuchun , Tian Ya , Shi Wen , Zhu Chunxiao , Lei Min , Zeng Rui , Zhang Chen , Qu Yan 
Published: July 2024

Abstract
The skin stratum corneum (SC) barrier function will interfere with the absorption of topical treatment and reduce the drug's therapeutic effect on alopecia. Microneedles (MNs) can penetrate the skin barrier and deliver drugs to the dermis. Furthermore, MNs can mechanically stimulate the skin, which promotes hair growth. Thus, we designed a green and dissolvable composite microneedle made of hyaluronic acid (HA) and Bletilla striata polysaccharide (BSP) to encapsulate cholesterol-free ginsenoside Rg3 liposomes (Rg3-LPs) to avoid cholesterol metabolism-producing testosterone to inhibit hair regeneration and minimize the effect of the SC barrier on liposomes absorption. HA and BSP can enhance the mechanical strength of Rg3-MNs to ensure the transport of liposomes to the hair follicle (HF) region while causing minimal skin irritation and guaranteeing cell compatibility. In addition, HA increased hair density and was more conducive to hair regeneration. In telogen effluvium (TE) and testosterone-induced androgenetic alopecia (AGA) animals, Rg3-MNs achieved comparable efficacy to minoxidil with low-frequency treatment and the quality of regenerated hair was higher. Furthermore, quantitative characterization and transcriptome sequencing results showed that Rg3-MNs promoted hair regeneration by promoting the expression of Wnt3a and Wnt10b genes, activating the Wnt/β-catenin pathway. Therefore, Rg3-MNs present broad prospects in the treatment of alopecia.