bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential responses of disease‐related GRIN variants located in pore‐forming M2 domain of N‐methyl‐D‐aspartate receptor to FDA‐approved inhibitors
Authors: Song Rui , Zhang Jin , Perszyk Riley E. , Camp Chad R. , Tang Weiting , Kannan Varun , Li Jia , Xu Yuchen , Chen Jiahui , Li Yinlong , Liang Steven H. , Traynelis Stephen F. , Yuan Hongjie 
Published: August 2023

AbstractN‐methyl‐D‐aspartate receptors (NMDAR), ionotropic glutamate receptors, mediate a slow component of excitatory synaptic transmission in the central nervous system and play a key role in normal brain function and development. Genetic variations in GRIN genes encoding NMDAR subunits that alter the receptor's functional characteristics are associated with a wide range of neurological and neuropsychiatric conditions. Pathological GRIN variants located in the M2 re‐entrant loop lining the channel pore cause significant functional changes, the most consequential alteration being a reduction in voltage‐dependent Mg2+ inhibition. Voltage‐dependent Mg2+ block is a unique feature of NMDAR biology whereby channel activation requires both ligand binding and postsynaptic membrane depolarization. Thus, loss of NMDAR Mg2+ block will have a profound impact on synaptic function and plasticity. Here, we choose 11 missense variants within the GRIN1, GRIN2A, and GRIN2B genes that alter residues located in the M2 loop and significantly reduce Mg2+ inhibition. Each variant was evaluated for tolerance to genetic variation using the 3‐dimensional structure and assessed for functional rescue pharmacology via electrophysiological recordings. Three FDA‐approved NMDAR drugs—memantine, dextromethorphan, and ketamine—were chosen based on their ability to bind near the M2 re‐entrant loop, potentially rectifying dysregulated NMDAR function by supplementing the reduced voltage‐dependent Mg2+ block. These results provide insight of structural determinants of FDA‐approved NMDAR drugs at their binding sites in the channel pore and may further define conditions necessary for the use of such agents as potential rescue pharmacology.image
Gray divorce and parent–child disconnectedness: Implications for depressive symptoms
Authors: Lin I‐Fen , Brown Susan L. , Mellencamp Kagan A. 
Published: August 2023

AbstractObjectiveDrawing on the divorce‐stress‐adjustment framework, the authors assessed whether parent–adult child relationship dynamics, including disconnectedness from an adult child, exacerbates the negative impact of gray divorce on parental well‐being.BackgroundDivorce after age 50 is increasingly common but the role of parent–child relationships in parents' adjustment to gray divorce is largely unknown.MethodUsing panel data from 1998 to 2018 Health and Retirement Study in the US, the authors estimated growth curve models to track depressive symptoms prior to, during, and after gray divorce among 930 gray divorced individuals. The authors examined whether the lack of any contact with an adult child in the past 12 months (i.e., parent–child disconnectedness) was associated with depressive symptoms trajectories surrounding divorce and subsequent repartnering.ResultsHaving no contact with at least one adult child aggravated the negative effect of divorce on parent's mental health. This association was robust for mothers and fathers. Having no contact with at least one child, however, did not diminish the temporarily positive effect of subsequent repartnering on mental health.ConclusionThe study contributes to the literature by showing that parent–child disconnectedness adds another blow to parents who are convalescing from divorce.
Future‐oriented temporal perspective promotes wise reasoning
Authors: Zhang Haotian , Glassman Harley , Ji Li‐Jun , Huang Chengli , Hu Chao S. 
Published: August 2023

AbstractObjectiveAcross three experiments (N = 622), we investigated the effect of the future temporal perspective on wise reasoning within the context of interpersonal conflicts.MethodStudies 1 and 2 applied two heterogeneous measurements of wise reasoning: self‐report and open‐ended measurements. Participants reasoned about their recent interpersonal conflicts from a future (i.e., 1 year from now) or a present perspective. Similarly, Study 3 tested the relationship between various future temporal distances (i.e., 1 week, 1 year, 10 years, 30 years from now) and wise reasoning.ResultsThe future temporal perspective significantly promoted wise reasoning compared to the present perspective, especially when the focus was 30 years in the future. Moreover, reasoning about a conflict event from a future perspective first might cause a carry‐over effect on reasoning from the present perspective later.ConclusionFuture‐oriented temporal perspective significantly improves wise reasoning.
SUMOylation of yeast Pso2 enhances its translocation and accumulation in the mitochondria and suppresses methyl methanesulfonate‐induced mitochondrial DNA damage
Authors: Somashekara Shravanahalli C. , Dhyani Kshitiza M. , Thakur Manoj , Muniyappa Kalappa 
Published: August 2023

AbstractSaccharomyces cerevisiae Pso2/SNM1 is essential for DNA interstrand crosslink (ICL) repair; however, its mechanism of action remains incompletely understood. While recent work has revealed that Pso2/Snm1 is dual‐localized in the nucleus and mitochondria, it remains unclear whether cell‐intrinsic and ‐extrinsic factors regulate its subcellular localization and function. Herein, we show that Pso2 undergoes ubiquitination and phosphorylation, but not SUMOylation, in unstressed cells. Unexpectedly, we found that methyl methanesulfonate (MMS), rather than ICL‐forming agents, induced robust SUMOylation of Pso2 on two conserved residues, K97 and K575, and that SUMOylation markedly increased its abundance in the mitochondria. Reciprocally, SUMOylation had no discernible impact on Pso2 translocation to the nucleus, despite the presence of steady‐state levels of SUMOylated Pso2 across the cell cycle. Furthermore, substitution of the invariant residues K97 and K575 by arginine in the Pso2 SUMO consensus motifs severely impaired SUMOylation and abolished its translocation to the mitochondria of MMS‐treated wild type cells, but not in unstressed cells. We demonstrate that whilst Siz1 and Siz2 SUMO E3 ligases catalyze Pso2 SUMOylation, the former plays a dominant role. Notably, we found that the phenotypic characteristics of the SUMOylation‐defective mutant Pso2K97R/K575R closely mirrored those observed in the Pso2Δ petite mutant. Additionally, leveraging next‐generation sequencing analysis, we demonstrate that Pso2 mitigates MMS‐induced damage to mitochondrial DNA (mtDNA). Viewed together, our work offers previously unknown insights into the link between genotoxic stress‐induced SUMOylation of Pso2 and its preferential targeting to the mitochondria, as well as its role in attenuating MMS‐induced mtDNA damage.
Autologous Costal Osteochondral Transplantation for Cystic Osteochondral Lesions of the Talus: Feasible and Effective
Authors: Wei Yuxuan , Guo Hao , Sun Nian , Tang Zhu , Ding Jianyang , Zeng Canjun 
Published: August 2023

ObjectiveOsteochondral lesions of the talus (OLT) is a common and clinically challenging disease. The optimal management is still under debate. The purpose of this prospective study was to investigate the feasibility and clinical outcomes of autologous costal osteochondral transplantation (ACOT) for the treatment of cystic OLT.MethodsFrom November 2021 to April 2023, five patients underwent autologous costal osteochondral transplantation (ACOT) for cystic OLT. The demographic data was described, including age, gender, lesion size and location. We prospectively evaluated their functional and imaging outcomes of the five patients for 12 months postoperatively, including numeric rating score (NRS) for pain when walking, Tegner score, American Orthopedic Foot & Ankle Society (AOFAS) score and Foot and Ankle Ability Measure (FAAM) score, and imaging results. A paired t‐test was used for preoperative and postoperative comparison of the paired‐design dataset.ResultsThe average age was 36.6 ± 11.1 years. The average diameter of chondral lesions was 14.95 ± 2.71 mm, the average diameter of subchondral cysts was 10.66 ± 1.84 mm, and their average depth was 10.40 ± 1.86 mm. At 12 months postoperatively, the clinical function indexes improved significantly, including NRS (from 5.2 ± 2.3 to 0), Tegner score (from 3.2 ± 0.4 to 5.8 ± 0.4), AOFAS score (from 72.8 ± 10.0 to 98.2 ± 4.0), and FAAM score (FAAM/ADL from 61.2 ± 24.7 to 99.3 ± 1.6; FAAM/Sports from 32.5 ± 13.73 to 96.3 ± 8.4). Their magnetic resonance observation of cartilage repair tissue (MOCART) scores reached 78.0 ± 7.6 points. ICRS scores of three patients were nearly normal (10 or 11 points). The biopsy of the surviving grafts showed plenty of hyaline cartilage matrix and scattered chondrocytes histologically. No major severe complications were reported during the 12 months follow‐up.ConclusionACOT could significantly relieve the symptoms of patients with OLT and improve their clinical function at short‐term follow‐up. ACOT might be a feasible and useful method for repairing OLT with subchondral cysts.
Adult host‐plant preference and larval performance in an oligophagous insect (Chnootriba elaterii)
Authors: Piersanti Silvana , Saitta Valerio , Rebora Manuela , Salerno Gianandrea 
Published: August 2023

AbstractThe present research investigates host preferences and larval development of the melon ladybird Chnootriba elaterii (Rossi) (Coleoptera: Coccinellidae), considering seven Cucurbitaceae plant species (Citrullus lanatus, Cucumis melo, Cucumis sativus, Cucurbita pepo, Cucurbita moschata, Lagenaria siceraria and Luffa aegyptiaca), to determine whether mother host preference is related with larval performance. The damaged area on plant leaves due to insect feeding in dual‐choice experiments was used to evaluate food preferences. Behavioural experiments in a Y‐tube olfactometer tested the role of olfaction in host‐plant selection. Parameters such as development duration and morphometric characters of emerged adults were evaluated to estimate larval performance. Adult females selected watermelon and melon as their favourite food while firmly refusing loofah and calabash. Insects preferred melon over watermelon, but the larval development on melon was slower; moreover, watermelon allowed larvae to develop faster than other tested plants, while loofah did not allow larval development. Larvae fed and developed on melon, pumpkin, zucchini, cucumber and calabash, without strong differences. These results only partially supported the preference‐performance hypothesis suggesting that it could be context dependent. Contrary to expectation, volatile organic compounds (VOCs) belonging to the host, only partially could guide adult females in the olfactometer. This result suggests that long‐distance olfactory stimuli alone cannot provide sufficient information for host‐plant selection in melon ladybirds. Considering the economic relevance of C. elaterii, the results of the present paper answer some basic questions about host‐plant selection for this pest insect, potentially useful to improve control strategies in crops.
Dihydrochalcone glycoside biosynthesis in Malus is regulated by two MYB‐like transcription factors and is required for seed development
Authors: Wang Yule , Ding Yuduan , Zhao Qian , Wu Chen , Deng Cecilia H. , Wang Jingru , Wang Yufan , Yan Yanfang , Zhai Rui , Yauk Yar‐Khing , Ma Fengwang , Atkinson Ross G. , Li Pengmin 
Published: August 2023

SUMMARYDihydrochalcones (DHCs) including phlorizin (phloretin 2′‐O‐glucoside) and its positional isomer trilobatin (phloretin 4′‐O‐glucoside) are the most abundant phenylpropanoids in apple (Malus spp.). Transcriptional regulation of DHC production is poorly understood despite their importance in insect‐ and pathogen‐plant interactions in human physiology research and in pharmaceuticals. In this study, segregation in hybrid populations and bulked segregant analysis showed that the synthesis of phlorizin and trilobatin in Malus leaves are both single‐gene‐controlled traits. Promoter sequences of PGT1 and PGT2, two glycosyltransferase genes involved in DHC glycoside synthesis, were shown to discriminate Malus with different DHC glycoside patterns. Differential PGT1 and PGT2 promoter activities determined DHC glycoside accumulation patterns between genotypes. Two transcription factors containing MYB‐like DNA‐binding domains were then shown to control DHC glycoside patterns in different tissues, with PRR2L mainly expressed in leaf, fruit, flower, stem, and seed while MYB8L mainly expressed in stem and root. Further hybridizations between specific genotypes demonstrated an absolute requirement for DHC glycoside production in Malus during seed development which explains why no Malus spp. with a null DHC chemotype have been reported.
AND THE WORDS BECOME FLESH: EXPLORING A BIOLOGICAL METAPHOR FOR THE BODY OF CHRIST
Authors: Mackay Deborah J. G. 
Published: August 2023

AbstractAlthough every cell in a human body contains the same DNA, every cell uses its DNA differently, in unique interaction with its environment. Human bodies live and thrive because their cells and tissues are sustained in a whole whose life emerges from, but cannot be reduced to, its parts. Living creatures are organized systems of processes that maintain their identity not despite change but because of it. These biological observations resonate with the foundational New Testament metaphor of the Body of Christ and with process‐theological descriptions of creatures as open‐ended processes interacting within a creation itself sustained within the boundless loving creativity of the Creator. I will map contemporary biological understanding of bodies as emergent and processual onto the theological metaphor of the Body of Christ and explore the ideas that emerge in terms of relationships between scripture, communities, and the life of the church.
Does time to theater matter in simple gastroschisis?
Authors: O'Shea Kathryn , Harwood Rachel , O’Donnell Sean , Baillie Colin 
Published: August 2023

ObjectiveA recent publication has suggested that expedited time to theater in gastroschisis results in higher rates of primary closure and decreases the length of stay (LOS). This study primarily aims to assess the impact of time to first management of neonates with gastroschisis on the LOS.MethodsNeonates admitted between August 2013 and August 2020 with gastroschisis were included. Data were collected retrospectively, and neonates with complex gastroschisis were excluded. Variables including gestation, birth weight, time of first management, primary/delayed closure and use of patch were evaluated as possible confounding variables. The outcome measures were time to full feeds, time on parenteral nutrition (PN) and LOS. Univariate and multivariate linear regression analyses were performed. P<0.05 was regarded as significant.ResultsEighty-six neonates were identified, and 16 were then excluded (eight patients with complex gastroschisis, eight patients with time to first management not documented). The median LOS for those who underwent primary closure was 21 days (interquartile range (IQR) =16–29) and for those who underwent silo placement and delayed closure was 59 days (IQR=44–130). The mean time to first management was 473 min (standard deviation (SD) =146 min), with only 20% of these infants being operated on at less than 6 hours of age. Univariate and multivariate analyses demonstrated no relationship between time to first management and LOS (r2=0.00, p=0.82) but did demonstrate a consistent positive association between time to first feed and LOS and delayed closure, resulting in a longer time to full feeds and a longer time on PN.ConclusionsThe time to first management was not associated with a change in LOS in these data. Further prospective evaluation of the impact of reducing the time to first feed on the LOS is recommended.Level of evidenceIV.
FP²: Fully in-Place Functional Programming
Authors: Lorenzen Anton , Leijen Daan , Swierstra Wouter 
Published: August 2023

As functional programmers we always face a dilemma: should we write purely
functional code, or sacrifice purity for efficiency and resort to in-place
updates? This paper identifies precisely when we can have the best of both
worlds: a wide class of purely functional programs can be executed safely using
in-place updates without requiring allocation, provided their arguments are not
shared elsewhere.
We describe a linear _fully in-place_ (FIP) calculus where we prove that we can
always execute such functions in a way that requires no (de)allocation and uses
constant stack space. Of course, such a calculus is only relevant if we can
express interesting algorithms; we provide numerous examples of in-place
functions on datastructures such as splay trees or finger trees, together with
in-place versions of merge sort and quick sort.
We also show how we can generically derive a map function over _any_ polynomial
data type that is fully in-place. Finally, we have implemented the rules of the
FIP calculus in the Koka language. Using the Perceus reference counting garbage
collection, this implementation dynamically executes FIP functions in-place
whenever possible.
Trustworthy Runtime Verification via Bisimulation (Experience Report)
Authors: Scott Ryan G. , Dodds Mike , Perez Ivan , Goodloe Alwyn E. , Dockins Robert 
Published: August 2023

When runtime verification is used to monitor safety-critical systems, it is essential that monitoring code behaves correctly. The Copilot runtime verification framework pursues this goal by automatically generating C monitor programs from a high-level DSL embedded in Haskell. In safety-critical domains, every piece of deployed code must be accompanied by an assurance argument that is convincing to human auditors. However, it is difficult for auditors to determine with confidence that a compiled monitor cannot crash and implements the behavior required by the Copilot semantics.
In this paper we describe CopilotVerifier, which runs alongside the Copilot compiler, generating a proof of correctness for the compiled output. The proof establishes that a given Copilot monitor and its compiled form produce equivalent outputs on equivalent inputs, and that they either crash in identical circumstances or cannot crash. The proof takes the form of a bisimulation broken down into a set of verification conditions. We leverage two pieces of SMT-backed technology: the Crucible symbolic execution library for LLVM and the What4 solver interface library. Our results demonstrate that dramatically increased compiler assurance can be achieved at moderate cost by building on existing tools. This paves the way to our ultimate goal of generating formal assurance arguments that are convincing to human auditors.
Modularity, Code Specialization, and Zero-Cost Abstractions for Program Verification
Authors: Ho Son , Fromherz Aymeric , Protzenko Jonathan 
Published: August 2023

For all the successes in verifying low-level, efficient, security-critical code, little has been said or studied about the structure, architecture and engineering of such large-scale proof developments.
We present the design, implementation and evaluation of a set of language-based techniques that allow the programmer to modularly write and verify code at a high level of abstraction, while retaining control over the compilation process and producing high-quality, zero-overhead, low-level code suitable for integration into mainstream software.
We implement our techniques within the F proof assistant, and specifically its shallowly-embedded Low toolchain that compiles to C. Through our evaluation, we establish that our techniques were critical in scaling the popular HACL library past 100,000 lines of verified source code, and brought about significant gains in proof engineer productivity.
The exposition of our methodology converges on one final, novel case study: the streaming API, a finicky API that has historically caused many bugs in high-profile software. Using our approach, we manage to capture the streaming semantics in a generic way, and apply it “for free” to over a dozen use-cases. Six of those have made it into the reference implementation of the Python programming language, replacing the previous CVE-ridden code.
More Fixpoints! (Functional Pearl)
Authors: Breitner Joachim 
Published: August 2023

Haskell’s laziness allows the programmer to solve some problems naturally and declaratively via recursive equations. Unfortunately, if the input is “too recursive”, these very elegant idioms can fall into the dreaded black hole, and the programmer has to resort to more pedestrian approaches.
It does not have to be that way: We built variants of common pure data structures (Booleans, sets) where recursive definitions are productive. Internally, the infamous unsafePerformIO is at work, but the user only sees a beautiful and pure API, and their pretty recursive idioms – magically – work again.
Etna: An Evaluation Platform for Property-Based Testing (Experience Report)
Authors: Shi Jessica , Keles Alperen , Goldstein Harrison , Pierce Benjamin C. , Lampropoulos Leonidas 
Published: August 2023

Property-based testing is a mainstay of functional programming, boasting a rich literature, an enthusiastic user community, and an abundance of tools — so many, indeed, that new users may have difficulty choosing. Moreover, any given framework may support a variety of strategies for generating test inputs; even experienced users may wonder which are better in a given situation. Sadly, the PBT literature, though long on creativity, is short on rigorous comparisons to help answer such questions.
We present Etna, a platform for empirical evaluation and comparison of PBT techniques. Etna incorporates a number of popular PBT frameworks and testing workloads from the literature, and its extensible architecture makes adding new ones easy, while handling the technical drudgery of performance measurement. To illustrate its benefits, we use Etna to carry out several experiments with popular PBT approaches in both Coq and Haskell, allowing users to more clearly understand best practices and tradeoffs.
Negotiating Catholic Sexual Ethics
Authors: Mapasure Martha , Dillen Annemie 
Published: August 2023

Abstract
Catholic teachings on sexuality have long stirred controversies and global debates insofar as they put the value of women’s sexual and reproductive health and rights into question. In the Catholic Church, there are ongoing debates among scholars, including theologians and feminists. Various theologians, such as Tina Beattie, have argued that the Church’s doctrines on sexuality do not take into account the daily experiences of a large group of Catholics, especially in relation to the topic of birth control.
In this paper, we present a review of empirical studies on the topic of ‘lived sexual ethics.’ Using an integrative review method, we compared nine empirical studies on ordinary Catholic women’s views on and experiences with Catholic teachings on sexual ethics with three aims in mind. Firstly, we present the methodology and conceptual framework (agency) that the study used. Secondly, we present one strategy and four arguments of the Catholic women in nine different contexts. Lastly, we analyze which approaches to agency from each of these could be considered when reflecting on sexual ethics from the perspective of lived experiences of Catholics.