bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract We084: Deciphering the Molecular Code Underlining Postnatal Cardiomyocyte Maturation by an RNA Splicing Factor RBFox1
Authors: Huang Jijun , Lee Josh , Rau Christoph , Pezhouman Arash , Yokota Tomohiro , Miwa Hiromi , Feldman Matthew , Kong Tsz Kin , Yang Ziyue , Tay Woan Ting , Pushkarsky Ivan , KIM Kyungsoo , Parikh Shan , Udani Shreya , Soh Boon Seng , Gao Chen , Stiles Linsey , Shirihai Orian , Knollmann Bjorn , Ardehali Reza , Di Carlo Dino , Abel Dale , Wang Yibin
Published: October 2024

Mammalian hearts undergo major changes after birth during the perinatal period. While several extrinsic factors such as mechanical load, electrical stimulation, hormones, and nutrients have been implicated in this process, the intrinsic regulatory circuit governing cardiomyocyte postnatal maturation is largely unknown. Importantly, stem-cell derived cardiomyocytes commonly exhibit immaturity which is a major limiting factor for their application as disease models or cell therapy agents. Therefore, uncovering the intrinsic regulatory mechanism of mammalian cardiomyocyte maturation has significant implications in both basic cardiac biology and cell-based therapy and disease modeling.

In our recent analysis of the global transcriptome transition from neonatal to adult rat hearts, we found RNA splicing among the top changed pathways. Additionally, we found that expression of RBFox1, a cardiac enriched RNA splicing regulator, was significantly increased during the postnatal transition to adolescence. We further demonstrate that RBFox1 mediated post-transcriptional regulation has a potent effect to promote neonatal and stem-cell derived cardiomyocyte maturation. RNA-seq followed by Gene Ontology enrichment analysis showed that Rbfox1 led to differentially expressed genes enriched in cardiac contraction and conduction, sarcomere organization, K
+
ion import and muscle filament sliding, as well as differential isoform switches enriched in cardiac contraction and sarcomere structure. An evolutionarily conserved, temporal specific super enhancer exists upstream of cardiac
Rbfox1
, which is occupied by active epigenetic markers in the postnatal period. We have identified the tissue and temporal transcriptional activity of this super enhancer
in vitro
and
in vivo
. Several binding motifs of transcription factors are predicted within it and a key DNA fragment was identified to be essential for enhancer activity. A transgenic mouse strain has been established to facilitate the tracing of myocyte maturation
in vivo
by constructing a reporter system driven by a 4xSuperEnhancer-Rbfox1Promoter-tdTomato construct. In conclusion, we propose a mechanism that RBFox1 is an intracellular regulator with tissue- and temporal-specific expression patterns that regulates cardiac maturation by promoting alternative splicing that fine tunes the genetic code.
Abstract We088: Spatiotemporal analysis of cardiac progenitor cells reveals migratory characteristics during epithelial-mesenchymal transition
Authors: Li Jing , Zhang Ke
Published: October 2024

Introduction:
Congenital heart defects (CHD) are one of the most common types of birth defects, with a rising prevalence in mild types. The most frequent CHDs include anomalies in the cardiac outflow tract (OFT), which mainly derives from multipotent cardiac progenitor cells termed second heart field (SHF). Hence, dysregulation of highly synchronized, chronological sequence of proliferation and differentiation of SHF cells could lead to severe CHDs. As the SHF contributes entirely to the OFT, mutations in the SHF-related genes lead to major arterial pole defects which account for one third of CHDs in newborn children. Investigating how these genes regulate cell-cell behavior and communication is of vital importance.

Hypothesis and Methods:
In this study, we employed a multidimensional approach to assess the hypothesis that the dynamic behavior of SHFs is regulated by key genes implicated in CHD pathogenesis. Leveraging single-cell RNA sequencing (RNA-seq) data obtained from experimentally dissected mouse OFT, we delineated distinct epithelial-to-mesenchymal transition states within SHF cell populations. Additionally, we developed a quantitative metric to assess SHF cell’s migratory level and integrated it with spatial transcriptomic analyses to map the developmental trajectory of SHFs.

Results and Conclusion:
Through spatiotemporal analysis, we identified a panel of key genes associated with SHF migration, shedding light on the molecular mechanisms underlying OFT development during early embryonic stages. Furthermore, we leveraged the data from The Pediatric Cardiac Genomics Consortium (PCGC) study (phs001194.v3.p2) which comprises a large cohort of CHD patients (13716 participants) and a proportion of 21.68% identified with OFT obstruction in its sub-study. In conclusion, using these datasets and quantitative metric being developed, we validated the SHF-derived genes in the PCGC participants and revealed specific expression patterns of these genes associated with OFT-specific CHDs. These results would benefit the understanding of the genetic regulation of SHF proliferation and differentiation, which is crucial for early detection and precise surgical intervention in CHD patients.
Abstract We094: Acute Administration of The Novel Cardiac Sarcomere Modulator EDG-7500, Improves Ventricular Filling While Preserving LVEF In Dogs with Pacing Induced Left-Ventricular Systolic Dysfunction
Authors: Evanchik Marc , Emter Craig , Del Rio carlos , Roof Steve , St Clair Sydney , Russell Alan , Henze Marcus , Semigran marc
Published: October 2024

Introduction:
EDG-7500 is a cardiac sarcomere modulator that has been shown to slow early LV contraction and to improve diastolic filling, without directly inhibiting cardiac myosin. To assess the acute hemodynamic effects of EDG-7500 in a model of depressed systolic and diastolic LV function, we studied dogs with pacing-induced LV dysfunction before and after EDG-7500 administration.

Methods:
Beagle dogs (n = 7) underwent chronic RV pacing (180 to 240 ppm), and were studied, in sinus rhythm, at two levels of induced-dysfunction: mid-range EF (mEF, targeting 50%), and reduced EF (rEF, targeting 40%). At each level, animals were evaluated by echocardiography before and after administration of 0.3 mg/kg IV EDG-7500. Healthy beagle dogs served as disease controls (n = 7).

Results:
Post-pacing (Paced) dogs had depressed EF (mEF: 50 ± 4 and rEF: 40 ± 4 vs. 74 ± 1%, P < 0.05) and short-axis global circumferential strain (mEF: -23 ± 2 and rEF: -14 ± 2 vs. -33 ± 1%, P < 0.05), and elevated NT-proBNPs (mEF: 1,049 ± 319 and rEF: 4,236 ± 722 vs. 302 ± 27 pmol/L, P < 0.05) when compared vs. healthy dogs. Paced dogs had slower early diastolic mitral annular velocity (mean e’, mEF: 11.0 ± 0.9 and rEF: 8.4 ± 0.8 vs. 14.2 ± 0.7 cm/s, P < 0.05) and elevated E/e’ (mEF: 7.4 ± 0.7 and rEF: 8.4 ± 0.9 vs. 6.0 ± 0.2 n/u, P < 0.05), at similar heart rates. Acute EDG-7500 increased e’ (mean e’, mEF: +9 ± 2 and rEF: +12 ± 3%, P<0.05) and decreased E/e’ (mEF: -7 ± 2% and rEF: -9 ± 2%, P<0.05), with no detectable effects on EF (mEF: +3 ± 6% and rEF: -5 ± 3%, P=NS). There were no adverse clinical observations.

Conclusions:
Treatment with EDG-7500 was well tolerated in dogs with tachycardia-induced mid-range (mEF) and reduced LV systolic function (rEF). In both cases, EDG-7500 improved echocardiographic indices of early ventricular filling and filling pressures, without observable effect on systolic performance. This data supports exploration of the effects of EDG-7500 in patient populations with LV diastolic dysfunction and mild to moderately reduced cardiac systolic performance.
Abstract We102: Synthetic N-Acylurea Derivative Reduces Angiogenesis in Human Endothelial Cells by Talin Modulation
Authors: Hong Soon Jun , Park Hun
Published: October 2024

Talin is a focal adhesion protein that activates integrins and recruits other focal adhesion proteins. Talin regulates the interactions between integrins and the extracellular matrix, which are critical for endothelial cells during angiogenesis. In this study, we successfully synthesized a novel talin modulator, N-((2-(1H-indol-3-yl)ethyl)carbamoyl)-2-(benzo[d][1,3]dioxol-5-yloxy)acetamide, referred to as KCH-1521. KCH-1521 was determined to bind talin and modulate downstream signaling molecules of talin. After 24 hrs of treatment, KCH-1521 changed the cell morphology of HUVECs and reduced focal adhesion protein expression including vinculin and paxillin. Talin downstream signaling is regulated via FAK, AKT, and ERK pathways, however, treatment with KCH-1521 decreased phosphorylation of FAK, AKT, and ERK, leading to a reduction of cell proliferation, survival, and angiogenesis. Interestingly, the expression of various angiogenic genes was significantly decreased after treatment with KCH-1521. Also,
in vitro
tube forming assay revealed that KCH-1521 reduced angiogenic networks in a time-dependent manner. To investigate the reversibility of its effects, KCH-1521 was removed after treatment. HUVECs recovered their morphology through rearrangement of the cytoskeleton and the expression of angiogenic genes was also recovered. By further optimization and
in vivo
studies of KCH-1521, a novel drug of talin modulation could be used to achieve therapeutic anti-angiogenesis for vascular diseases and cancers.
Abstract We104: A New Small-Molecule ErbB4 Agonist Attenuates Adverse Ventricular Remodeling After Myocardial Infarction In a Sex-Specific Manner
Authors: Goovaerts Bo , Civati Celine , Feyen Eline , De Keulenaer Gilles , Segers Vincent
Published: October 2024

Background:
The beneficial effects of the neuregulin/ErbB pathway on the diseased heart have been well-established. The cardioprotective aspects of neuregulin are largely attributable to the activation of the ErbB4 receptor. We recently developed a small-molecule selective ErbB4 agonist, which reduced collagen production in fibroblasts and prevented oxidative-stress induced cardiomyocyte death
in vitro
.

Hypothesis:
We hypothesized that the ErbB4 agonist (referred to as compound, Cpd), would attenuate left ventricular remodeling, reduce interstitial cardiac fibrosis and preserve cardiac function in a murine model of myocardial infarction (MI). Since there is a potential interaction between the ErbB4 receptor and the estrogen receptor, we further hypothesized these effects would be sex-dependent.

Methods:
Mice were divided by sex and then further divided into three experimental groups: a sham group, an MI group receiving Cpd (MI/Cpd), and a control MI group receiving vehicle only (MI/Veh). Mice started treatment with either Cpd (2mg/kg/d) or its vehicle through subcutaneous osmotic minipumps seven days after MI. Cardiac ultrasound was performed weekly until mice were sacrificed after four weeks of treatment. Hearts were excised and stained with Masson’s trichrome to assess interstitial cardiac fibrosis in myocardium remote from the infarction scar.

Results:
In females (n=25), Cpd significantly decreased left ventricular end-diastolic volume compared to vehicle (Fig.1A, 80±23 µl vs.108±29µl, p=0.045) and induced a slightly increased left ventricular ejection fraction (Fig.2A, 32±12% vs. 22±9%, p=0.086). In addition, Cpd significantly reduced reactive interstitial fibrosis (fibrotic area, Fig.3A, 1.4±1.0% vs. vehicle: 3.8±3.1%, p=0.036) in females. In males (n=30), Cpd had no significant effects on either of the parameters mentioned above (Fig.1B, 2B, 3B).

Conclusion:
Treatment with the novel small-molecule ErbB4 agonist attenuates left ventricular dilation and reactive interstitial fibrosis after MI in female mice, but not in males. These data support the premise that small molecule-induced ErbB4 activation is a potential new therapy for heart failure, especially in female patients. The mechanisms underlying the sex-dependent effects warrant further exploration.
Abstract We114: Feeding Behavior Underlies the Circadian Rhythm in the Autonomic Input to the Heart and Heart Rate
Authors: Prabhat Abhilash , Stumpf Isabel , Stalcup Rebecca , Ehlman Allison , Seward Tanya , Pendergast Julie , Schroder Elizabeth , Delisle Brian
Published: October 2024

Objective:
The circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus drives circadian rhythms in feeding and activity. Several studies suggest the SCN regulates autonomic input to the heart to generate day-night rhythms in heart rate.

Hypothesis:
The circadian rhythm in feeding generates day-night rhythms in autonomic input to the heart and heart rate.

Methodology:
Mice (n=6/sex) were implanted with telemetry probes to continuously record heart rate, core body temperature, and activity in thermoneutral housing conditions. Mice were housed in a 12 h light: 12 h dark cycle (LD) with ad libitum access to food (ALF). In these conditions, mice primarily eat during the dark cycle. Mice were subjected to light phase time-restricted feeding (TRF) for 5 days. This forces the mice to eat during the light cycle. We quantified changes in autonomic input to the heart by injecting mice with the autonomic receptor inhibitors propranolol and methylatropine. To determine if circadian rhythms generate day-night rhythms in autonomic input to the heart, TRF mice were switched from LD to constant darkness (DD) and then returned to ALF in DD.

Results:
ALF mice housed in LD had 24-hour rhythms in autonomic input to the heart, heart rate, and activity that all peaked in alignment during the dark cycle. One day after starting TRF, the phase of the 24-hour rhythms in heart rate but not activity shifted by 8-10 hours to align with feeding during the light phase. Switching TRF mice in LD to DD did not alter the phase or amplitude of the day-night rhythms in autonomic input to the heart, heart rate, or activity. Returning the TRF mice in DD to ALF showed the autonomic input to the heart and heart rate re-aligned with the free running rhythm in activity.

Conclusions:
Day-night rhythms in heart rate and autonomic input to the heart align with activity in LD and DD in ad libitum fed but not time-restricted fed conditions. These data demonstrate that feeding behavior, not SCN-signaling or activity rhythms, drives day-night rhythms in autonomic input to the heart and heart rate.
Abstract We131: Systems-Enabled Drug Repurposing to Regulate Cardiomyocyte Proliferation
Authors: Wintruba Kaitlyn , Saucerman Jeffrey
Published: October 2024

Introduction:
The inability of the adult heart to regenerate results in prevalent morbidity and mortality related to myocardial infarction and heart failure. This lack of cardiac regeneration is driven by the loss of cardiomyocytes (CMs), with limited supporting endogenous CM renewal. While many individual regulators of CM proliferation have been implicated, the field lacks strategies to identify druggable proliferative signaling pathways and prioritize candidate therapeutics. Our goal is to predict and experimentally validate FDA-approved drugs and their respective mechanisms that regulate CM proliferation.

Methods:
A logic-based differential equation model of CM proliferation signaling was integrated with drug-target interactions from a publicly available database (DrugBank) to simulate the effect of drugs on CM proliferation phenotypes (Binucleation, Cytokinesis, DNA Replication, Mitosis, and Polyploid). A virtual screen with knockdown combinations of regulators identified signaling mechanisms responsible for mediating the effect of drugs, and literature validation was performed against published experimental data investigating the drugs or the drug targets in CMs. Neonatal rat CMs were treated with the YAP-activating drug TT10 or drugs predicted to increase CM proliferation. Proliferation was measured by high-content microscopy and DNA replication and mitosis positive cells were identified from image analysis (CellProfiler) to discern CM proliferation from endoreplication.

Results:
We identified 16 unique drug-target interactions predicted to regulate CM proliferation phenotypes. Four drugs were predicted to increase CM phenotypic proliferation outputs. Experimental validation confirmed lithium, a GSK3beta-antagonist, induces cell cycle activity in neonatal rat CMs as evidenced by increased Ki67 expression in cardiac Troponin T positive cells. The model predicts cyclin D is critical in mediating this response and subsequent experiments measured changes in cyclin D expression in response to lithium treatment. Retrospective analysis of clinical data (TriNetX and AERSMine) indicates more adverse events of congenital cardiac disorders were reported in patients exposed to lithium.

Conclusion:
We identified lithium to promote DNA replication in CMs by upregulating cyclin D. This study advances the current knowledge of CM proliferation regulators by providing insight into new pathways targeted with existing drugs that can ultimately impact cardiac regeneration.
Abstract We136: HnRNPA1 Modulates Expression of Myogenic Differentiation Factors by Maintenance of
Ppp1r1b
-
lncRNA
/PRC2 Complex Integrity
Authors: Kang Xuedong , Zhao Yan , Touma Marlin
Published: October 2024

Objective:
HnRNPA1 is an important member of the HNRNP family, serves multiple functions. The long noncoding RNA
Ppp1r1b
is a key regulator of myogenesis in cardiac and skeletal muscle development. This study aimed to investigate the role of hnRNPA1 in
Ppp1r1b-lncRNA
mediated myogenesis and identify the underlying molecular mechanisms.

Methods:
Ppp1r1b-lncRNA
:

protein complex was isolated by RNA pulldown assay. The corresponding proteins were identified by mass spectrometry. The binding sites of hnRNPA1 and EZH2 on
Ppp1r1b-lncRNA
were further evaluated by RNA pulldown assay and western blotting. After downregulation of hnRNPA1, expression of muscle development related genes was measured by qRT-PCR and western blot analysis. Furthermore, EZH2 RIP (RNA Immunoprecipitation), H3K27me3 CHIP (Chromatin Immunoprecipitation) and
Ppp1r1b-lncRNA
CHIRP (Chromatin Isolation by RNA Purification) were applied.

Results:
HnRNPA1 and EZH2 both bind to
Ppp1r1b-lncRNA
and their bindng sites are located at different positions. EZH2 RIP assay and H3K27me3 CHIP show decreased
Ppp1r1b-lncRNA
/EZH2 interaction and corresponded decreased H3K27me3 modification after downregulation of hnRNPA1. The expression of myogenic diffrentiation related genes was significantly suppressed by hnRNPA1-RNAi while CHIRP assay indicated elevated interaction of
Ppp1r1b-lncRNA
with
Myod1
and
Myogenin
promoter.

Conclusions:
HnRNPA1 facilitates the integrity of
Ppp1r1b-lncRNA
/PRC2 complex, which preserves correct regulation of myogenesis gene expression. After hnRNPA1 suppression, the elevated promoter occupancy of
Ppp1r1b-
lncRNA corresponds with transcriptional repression. The hnRNPA1/
Ppp1r1b lncRNA
/PRC2 complex regulatory axis is a potential therapeutic target during heart and skeletal muscle development.
Abstract We138: Single-nucleus and bulk multiomic analyses reveal the dynamics of individual cardiac cell types after myocardial infarction and the underlying gene regulatory networks
Authors: Li Yuxia , Wang Leshan , Liu Qianglin , Zhang Xujia , Gao Peidong , Sun Jiangwen , Fu Xing
Published: October 2024

Cardiovascular diseases are the leading causes of death in the world, among which myocardial infarction (MI) is the most fatal form. Following MI, the death of cardiomyocytes induces cardiac remodeling, which is mainly mediated by cardiac fibroblasts but also involves other cardiac cell types. A deeper understanding of the dynamics of individual cell types among different stages after myocardial infarction may help identify novel therapeutic strategies. Here, through single-nucleus multiomic (snRNAseq and snATACseq) analysis of uninjured mouse hearts and mouse hearts at different time points (2 h, 1 d, 3 d, 7 d, and 4 w) after MI, we identified multiple cardiac cell types, including cardiomyocyte, fibroblast, epicardial cell, endothelial cell, mural cell, and immune cell, and their dynamic gene expression and chromatin accessibility after MI. Features specific to the acute and chronic responses of different cell types to MI were identified. Cell type-specific single-nucleus gene regulatory networks (snGRNs) constructed through integrated analysis of snRNAseq and snATACseq data revealed transcription factors possibly responsible for the gene expression changes in individual cell types. The cardiac fibroblast GRN was further enriched using bulk RNAseq and ATACseq data collected at more time points (uninjured, and 2 h, 12 h, 1 d, 3 d, 7 d, 2 w, and 4 w after MI) and non-coding RNA transcriptomics. Promoter and enhancer activities and chromatin interactions in cardiac fibroblasts were further verified by CUT&Tag targeting corresponding histone markers and Hi-C, respectively. The refined cardiac fibroblast GRN identified multiple key transcription factors that likely govern cardiac fibroblast activation and differentiation after MI.
Abstract We145: δ-catenin mRNA m
6
A Methylation Promotes Cardiac Fibrosis following Acute Myocardial Infarction
Authors: Dutta Roshan , Ranjan Prabhat , Pathak Vasundhara , Colin Karen , zhang qinkun , Xie Min , Lal Hind , young martin , Verma Suresh
Published: October 2024

Background:
Cardiac fibrosis is pivotal in heart failure progression, where excessive extracellular matrix (ECM) secretion by activated fibroblasts leads to adverse remodeling and dysfunction. While Wnt/β-catenin signaling influences fibroblast activation and cardiac fibrosis post-MI, its precise regulation remains unclear. Emerging evidence suggests N6-methyladenosine (m
6
A) mRNA methylation's role in disease pathology, yet its specific contribution to post-MI cardiac fibrosis is not well understood. Thus, we

hypothesized

that “
MI-induced METTL3 (a Key m6A mRNA methyltransferase) activation stabilizes δ-catenin mRNA, facilitating cardiac fibrosis and adverse remodeling
”.

Methods:
The mice underwent sham/MI surgeries for 4 weeks, after which heart tissues were collected for biochemical and histological analysis following heart function measurements. Additionally, methyl-immunoprecipitation followed by RNA sequencing (MeRIP-sequencing) was performed on the heart tissue post-surgery, and the data were analyzed to identify fibrosis-associated targets.

Results:
Ischemic injury significant increase in m6A mRNA methylation in heart tissues. This increase in m
6
A RNA was also observed in adult cardiac fibroblasts (AMFs) following TGFb treatment. Interestingly, METTL3 inhibition (METTL3 siRNA) resulted in a significant reduction in TGFb-induced periostin and fibronectin gene expression, while METTL3 overexpression enhanced the expression of fibrotic genes in AMFs. To identify differentially regulated m6A target genes, MeRIP-seq was performed on RNA isolated from mice hearts post-MI. The sequencing data suggested hypermethylation of fibrosis-associated genes, including δ-catenin, post-MI. Notably, TGFb-induced increased δ-catenin mRNA methylation led to δ-catenin mRNA stabilization. In contrast, METTL3 inhibition using siMETTL3 in AMFs and in METTL3 KO mice significantly reduced fibroblast activation and cardiac fibrosis.

Conclusion:
Our data suggests that hypermethylation of δ-catenin mRNA plays a significant role in the progression of cardiac fibrosis following AMI. Therefore, regulating METTL3 could be a potential therapeutic target for attenuating cardiac fibrosis.
Quantum mutati! Hector, Pompey, and the Fortune of a Mut(il)ation
Authors: Pontiggia Ludovico
Published: October 2024

This article collects various passages of the Pharsalia in which Lucan alludes to the apparition of Hector’s mutilated shade, portrayed by Aeneas in Aeneid 2 as deeply changed from the relentless hero of the Iliad, and uses it as a model for the tragic fall from glory that republican Rome and Pompey have undergone throughout the civil war. Following up on metapoetic interpretations of Aeneas’ dream, it is then argued that in the Pharsalia, too, Hector’s ghost functions as an intertextual marker flagging up the Virgilian model, and symbolises the transition from a type of epic aimed at celebrating the winners to Lucan’s epic of the losers.
Seven new species of the enigmatic spider genus Paratropis Simon, 1889 (Mygalomorphae, Paratropididae) from Ecuador
Authors: DUPÉRRÉ NADINE , TAPIA ELICIO
Published: October 2024

Seven new species of the enigmatic spider family Paratropididae are described from Ecuador. All new species belong to the genus Paratropis: P. carcosita sp. nov. (♀), P. pukallucha sp. nov. (♂♀), P. esmeraldas sp. nov. (♂♀), P. kapak sp. nov. (♂♀), P. pasochoa sp. nov. (♀), P. arenosa sp. nov. (♀) and P. cryptica sp. nov. (♂♀). A distribution map of all newly described species is presented.
A remarkable new genus of Sciomyzoidea from Japan, with discussion of its taxonomic position (Diptera, Acalyptratae)
Authors: SAIGUSA TOYOHEI
Published: October 2024

An acalyptrate fly, Babakintaromyia albitarsis gen. et sp. nov., of the superfamily Sciomyzoidea is described from Japan. Wing venation is similar to that of the sciomyzid genus Salticella Robineau-Desvoidy, but the species differs abundantly from Salticella in other respects. Taxonomic characters of the new species differ from those of most or all species of Sciomyzidae in some important ways, including the absence of a preapical dorsal seta on all tibiae. The new genus is tentatively assigned to the subfamily Salticellinae of the Sciomyzidae.
6. Iannis Xenakis’s Free Stochastic Music Program as an Aid to Analysis
Authors: Squibbs Ronald
Published: October 2024

In 1962, Xenakis composed five works with the assistance of a computer program that he titled Free Stochastic Music. Xenakis provided the code for the program, as well as other documentation required to produce output, in Formalized Music and elsewhere. As with any computer program, the best way to understand its operation is to run it and to test its output against one’s expectations. Despite the documentation that Xenakis provided, it is not possible to run Free Stochastic Music on modern compilers without editing its code for compatibility. Even after this obstacle has been overcome, interpretation of the output requires some knowledge of the theoretical principles on which the stochastic compositional algorithm at the heart of the program was based. This chapter aims to provide a concise explanation of the operation of the program, using as input the data that Xenakis provided for the composition of Atrées. A musical transcription of some newly generated output is then tested for consistency with the program’s theoretical premises, as will the first movement of Atrées. Special emphasis is given to the crucial roles of texture and instrumentation in generating the characteristic sound of this repertoire.
7. Continuum versus Disruptum
Authors: Castanet Pierre Albert
Published: October 2024

While playing wonderfully with the various physical and metaphysical notions of the world, Iannis Xenakis conceived his own laws regarding the continuous/discontinuous conduct of the spatio-temporal references in his instrumental and vocal music. In this chapter, which voluntarily excludes electroacoustic music, the scores of Naama, Persephassa, Pithoprakta, Tetras, Nuits, Tracées, Jonchaies, Mikka, Mikka 'S, Metastasis, Thallein, Embellie, Eonta... are summoned and explored both on the aesthetic-philosophical and on the analytic-musicological level.
15. Game Theory and Formal Structure in Iannis Xenakis’s Duel (1959)
Authors: Malt Mikhail , Sluchin Benny
Published: October 2024

Game theory is the theoretical context of three compositions by Iannis Xenakis: Duel (1959), Stratégie (1962) and Linaia-Agon (1972). The first two works oppose two orchestras, or, more precisely two conductors, in a musical battle. The basic structure differs only in the size of the ensembles (Duel is written for two orchestras of twenty-eight musicians each, while Stratégie is composed for two orchestras of forty-six musicians each), the tactics (i.e., the musical material), and the complexity of the gain matrices. Linaia-Agon, for horn, trombone, and tuba is a later composition, combining completely determined parts with a part whose structure is determined by game theory. The general aspects of Duel, Stratégie, and Linaia-Agon having already been presented in other studies; here, we will mainly focus on the formal aspects of Duel and the structure resulting from the underlying use of the opposition model governed by game theory. This chapter takes a computational and empirical musicology approach and identifies the dynamics derived from the model with the performed musical structure. We carried out several computer simulations of Duel to study its behavior and the structures generated, according to the methods of ‘playing’. Duel is to be performed by two conductors who, per Xenakis’s instructions, make choices in real time. These choices must follow precise instructions in relationship to the ‘game matrix’ provided by the composer. From our point of view, the choices of the opponents, in the context of a performance, will have a significant influence on the musical form generated. The main purpose of our research is to be able to guide conductors on the different ‘outcomes of the battle’, according to their decisions.
31. UPISketch
Authors: Bourotte Rodolphe
Published: October 2024

When we consider the needs we may have in the field of electroacoustic music composition, a tool allowing a graphic representation of sound and musical phenomena seems interesting to develop. UPISketch is one of these tools. Part of this chapter focuses on describing the abundance of ideas that the development of such a tool can inspire. UPISketch is a subset of graphical score systems: it is positioned on the question of the graphical representation of quantitative data. It has the potential to update the breakthroughs that Xenakis made through his mathematical approach by making them newly accessible via intuitive graphic interfaces. New possibilities, not yet implemented in the software, will be evoked. Specifically, it is now possible to imagine an extension of the legacy of Xenakis's thinking on sieves and probabilities, in the graphic domain with UPISketch, in a junction that had never been realized with UPIC.
34. Light Tectonics
Authors: Yu Yin , Harris Conrad
Published: October 2024

Light in Iannis Xenakis’s work is poetic, dramatic, emotional, and powerful. Xenakis not only created a new aesthetic of light art, but also projected a future direction for the role of light in art. The Shape of Light, as a study of the form of digital light, presents visual music for the compositions Mikka (1971) and Mikka ‘S (1976). Two versions of our work are presented and compared: a pre-recorded and a live performance.
38. The Algorithmic Music of Iannis Xenakis–What’s Next?
Authors: Manaris Bill
Published: October 2024

Iannis Xenakis was a pioneer in algorithmic composition of music and art. He combined architecture, mathematics, music, and performance art to create avant-garde compositions and performances that are still being analyzed, performed widely, and discussed. Xenakis’s musical contributions are deeply algorithmic in nature, inspired by his understanding and appreciation of mathematics and controlled randomness; i.e., stochastic processes. His work was made possible through his use of early computer programming languages, such as FORTRAN and BASIC, and the formalization, standardization, and replicability such languages provide. This chapter explores the intersection of science and art, Xenakis’s early computational techniques for a non-technical audience, and how algorithmic music composition has advanced since his passing. It includes the retelling of one of his early works, Concret PH; a reimagining of UPIC; and musical examples derived from blending artificial intelligence, advanced algorithms, modern technology and smartphones, and user interaction, into the body of techniques introduced by him.
46. A New Documentary
Authors: Loufopoulos Apostolos , Dalianoudi Renata , Panagopoulos Iakovos , Marini Hari
Published: October 2024

The documentary produced by the Ionian University, Iannis Xenakis: Music of the Universe, which I directed, offers a fresh approach to Xenakis’s life and work, and contributes to a better understanding of his creative, unconventional, pioneering thinking and composing. Focusing on crucial political and social happenings in Xenakis’s life, this documentary—as a condensed study—yields new insight into the composer’s attitude and work. Through the ethnographic method of the interview, the interviewees’ statements reveal the extent to which social and political events formed Xenakis’s personal choices and aesthetics. Both the performance ‘interludes’, devised and directed by Hari Marini, and the sound design and music, written by Apostolos Loufopoulos, are works within the work, completely integrated. The modular performance represents in a more creative and impulsive way the three different parts/acts of Xenakis’s life as well as the emotional connotations that emerge with the help of the dense existence of music, while the soundtrack’s structure reflects Xenakis’s approach of massive sound-clouds and detailed sound entities.
47. Reportage of a UPISketch Workshop in Japan
Authors: Suzuki Yoshihisa
Published: October 2024

The Meta-Xenakis Japan Team held two UPISketch workshops in 2022. These contributed to disseminate Xenakis’s concept of the UPIC system to young Japanese musicians as well as to people who are not accustomed to contemporary music. Beforehand, in 2021, in collaboration with Rodolphe Bourotte (brainchild behind the UPISketch), one composition class, in which every student created a short piece using this application, had been realized at Nagoya City University. After the class, some students presented their pieces to the other students. Three of the students’ pieces were broadcast via YouTube in the online concert Nagoya Electronic Concerts 2021(NEMC2021). In the first workshop in 2022, twelve participants presented their pieces based on UPISketch. All the participants were university students studying media art and design. After the presentation of their pieces, they discussed how to manage a workshop for more general public having no experience in digital music. They made UPISketch user-manual texts in Japanese based on the UPISketch URL. This reportage presented here covers our second UPISketch workshop which was held on May 29, 2022, celebrating Xenakis’s 100th birthday. It was open to high school students and others interested in music as one type of contemporary media art. The workshop comprised an initiation to the application, free time for the participants’ creation, and evaluation of the pieces by some of the young composers. Participants were neither professional musicians nor sound designers, but all enjoyed drawing sound.
48. Polytope XXI
Authors: Marandola Fabrice , Boucher Myriam , Thibault Dominic
Published: October 2024

Polytope XXI is the title of a concert presented by Montreal-based percussion sextet Sixtrum to pay tribute to Iannis Xenakis. It is also the name that composers Myriam Boucher and Dominic Thibault have given to their monumental instrumental project that was premiered during this concert in May 2022: a sort of giant, electronically augmented, audio-luminescent harp, whose strings are put in vibration by multiple means by the percussionists of Sixtrum during the concert.

The project was inspired by the first Polytope imagined by Iannis Xenakis, an ‘electronic sculpture combining light, music, and structure’, that was presented inside the French Pavilion during Expo67—the World’s Fair that took place in Montreal in 1967. This original installation created an artistic work inscribed in space and made of multiple layers of sound and light, and was designed so that spectators could move freely within the installation itself. Polytope XXI inverts this approach and sets the installation on stage with the goal to make it mobile, so that changes in the perception of space, light and sound can still be experienced by the audience, while also taking advantage of modern technological capabilities (actuators, sensors, etc). Here, we present a live recording of the world premiere of this work.
Lightning Casualties of Vulnerable Caterpillar Fungus Collectors on the Qinghai–Tibetan Plateau
Authors: Zhang Daile , Holle Ronald L.
Published: October 2024

Lightning has killed and injured many people in recent years in the Qinghai–Tibetan Plateau area of China when they were collecting a rare product used for medical applications. The fungus that grows on dead caterpillars at high altitudes in this region demands a high price when sold, so it attracts collectors that unfortunately become at risk from lightning during this process. A total of 12 lightning-related events during 2004–22 resulted in 29 deaths and 53 injuries. All cases occurred at high elevations in rugged terrain with no available lightning-safe structures or vehicles. The fungus collection occurred during the daytime hours in late spring and early summer, which is also when lightning is frequent. Maps of lightning for the cases and information gained from the Chinese-language reports are summarized. It is apparent that this is a unique high-risk, high-reward occupation that is similar in terms of exposure to other situations around the world that result in lightning deaths and injuries.

Significance Statement

Lightning deaths and injuries often occur when people push the limits of safety due to occupational or recreational demands. Most of these decisions are on short time scales such as while tending agricultural fields, working on roofs, running a competitive race, or walking home from school when a thunderstorm is approaching. In the scenario presented here, groups of people with few income alternatives spend weeks or months in mountainous regions where lightning is common, but safety is elusive. This situation is an unusual version of high lightning risk occurring while pursuing a high reward.
Research on defect image inversion method based on multiple lift-off values magnetic memory signals
Authors: Shijie Deng , Hailong Chen , Wanfeng Gao , Zhaoyi Jiang , Xiaotao Zhang
Published: October 2024

Metal magnetic memory (MMM) technique can detect macroscopic defects and stress concentration zones of ferromagnets, and it can identify the approximate positions of these flaws, while a little further information about defects characteristics can be provided. To promote study in this area, defects were modeled as located magnetic dipoles whose strength and locations should be determined, and the technique of truncated generalized inverse and reduced space inversion were used to image the dipole strength. Through the simulation experiment, we found that the inversion image quality was influenced by the lift-off value. When the magnetic field data for inversion was measured with a small lift-off value, the inner dipoles contributions were easily buried and the inversion image can only shown the surface dipole well. In contrast, if the magnetic field data was measured with a greater lift-off value, it was possible to inverse the deep dipoles while the image was somewhat out of focus. To overcome this limitation, we composed the magnetic field data measured under different lift-off values together for inversion. We used the same model to test this approach and applied it on real crack defects magnetic field data. It demonstrates that the new inversion approach shows better accuracy than the single lift-off value and it was possible to infer the location and size of defect by the evaluation of preset dipoles.
Lifetime Achievement Response
Authors: Whiteman Darrell
Published: October 2024

This response notes my training as a missiological anthropologist and how I have used that to train people for cross-cultural ministry. I have drawn on the Incarnation of Jesus as a model for mission and note that I am grateful to American Society of Missiology for enabling me to serve in multiple capacities for 40 years.
Beyond a Slave: Support for the Manumission of Onesimus from Discourse Analysis
Authors: Arinder Devin
Published: October 2024

Did Paul intend for Philemon to manumit Onesimus? This article aims to present evidence in support of a manumissive view of Paul’s communicative intent to Philemon. Through a cognitive functional approach to discourse analysis, the sentence comprising vv. 15–16 is proposed to represent the peak of the epistle. Coincidingly, this central statement of the letter is precisely where Paul discusses the enslavement of Onesimus. There, through his linguistic choices, Paul construes emphatic discontinuity in Onesimus’s status, resulting in the most salient change in Philemon’s mental representation: Onesimus is no longer a slave, but beyond a slave, a beloved brother.
Optimal powertrain system design and V2V and V2I based hierarchical control strategy of FRIDEV under vehicle-following scenarios
Authors: Ma Chao , Yin Hang , Shang Yue , Cao Lei , Yang Kun
Published: October 2024

In this paper, the front- and rear-independent-drive electric vehicle (FRIDEV) is selected as the target vehicle for its good dynamic and economy performance. Based on the analysis of the cost, efficiency, and loss characteristics of different motors, the interior permanent magnet synchronous motor (IPMSM) and induction motor (IM) are applied in the target powertrain system. Then, the proposed powertrain system is optimized based on the analysis of driving cycles. The optimal control strategy for the target powertrain system is developed, which consists of the driving mode switching algorithm and the driving torque distribution based on adaptive particle swarm optimization (APSO). Furthermore, in order to achieve the efficient autonomous driving of the target vehicle under the vehicle-following scenarios, a hierarchical control strategy is proposed with the combination of upper-level control of the speed planning strategy and the lower-level control of powertrain system control strategy. The upper-level control of speed planning strategy is designed, which can determine and track the target vehicle speed based on the information from vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) communications. Finally, simulation analysis in MATLAB/Simulink and virtual driving experiments are conducted to verify the superiority of the proposed powertrain system and hierarchical control strategy.
Study on hybrid 3D printing and milling process for customized polyether-ether-ketone components
Authors: Sun Haoyi , Cheng Xiang , Liu Yuanyong , Dong Ruichun , Liu Huanbao , Zheng Guangming
Published: October 2024

Polyether-ether-ketone (PEEK) has been widely applied in various fields due to its excellent mechanical properties and biocompatibility. The efficient and high-quality customized manufacturing of PEEK components are investigated in this study by the hybrid 3D printing and milling process. At first, the alternating hybrid process is selected and verified by comparing two typical hybrid process categories and conducting experiments, respectively. Second, a set of procedures are designed to automate the engineering application of the hybrid process trying to avoid the disadvantages of manual programing. Then, considering the tool length and possible interferences during the hybrid process, a model segmentation algorithm, namely, the exchange principle of avoiding interference (EPAI) is proposed. Based on the introduced EPAI and the programing language Python, the additive and subtractive hybrid manufacturing (ASHM) data processing procedure is proposed and realized by post-processing of the conventional 3D printing codes. Finally, the feasibility experiments have been conducted. The experimental results verify the hybrid manufacturing process in the fabrication of parts with complex internal features. The surface roughness Ra and dimensional error L of the parts have been reduced by 75.5% and 85.2%, respectively, while the shear strength τ has been increased by 14.1%. Compared with conventional milling process, the material consumption is reduced by 48.7%.
Book review: Laura Stark and Annika Björnsdotter Teppo (Eds.), Power and Informality in Urban Africa: Ethnographic Perspectives
Authors: Ahmad Intikhab
Published: October 2024

Laura Stark and Annika Björnsdotter Teppo (Eds.), Power and Informality in Urban Africa: Ethnographic Perspectives (Zed Books Bloomsbury Publishing, 2022), 264 pp., $99.00 (Hardback); $30.95 (Paperback). ISBN: 9781786993441.
Public Support for State Challenges to National Laws
Authors: Wolak Jennifer
Published: October 2024

State governments are increasingly challenging the national government and pursuing state rules in opposition to national laws. I am interested in whether the public supports this strategy. Do people want state governments to deliver policy outcomes that better fit the interests of state constituents—even if it undercuts the authority of the national government? Or are citizens critical of state actions that challenge national laws? I find that most Americans do not believe that states should be allowed to block the enforcement of federal laws they disagree with. Opposition to state challenges increases with support for the rule of law. Using experiments, I explore whether people are less likely to support policy outcomes when they are described as challenging national provisions. I find limited evidence that people evaluate state policies differently when described as contrary to national laws. People support national supremacy in the abstract and accept state resistance to national mandates in practice.
Poster 139: A Prospective, Observational Study to Assess the Efficacy of BioEnthesis in Patients Undergoing Arthroscopic Rotator Cuff Repair
Authors: Haneberg Erik , Phillips Andrew , Danilkowicz Richard , Elias Tristan , Wang Zachary , Forsythe Brian , Garrigues Grant , Yanke Adam
Published: October 2024

Objectives:

Rotator cuff repair (RCR) remains an area needing further research to optimize patient outcomes postoperatively. This study investigates a novel allogenic, acellular, biphasic cancellous bone scaffold that lies between the tendon and bone in an RCR. The purpose of this study is to assess the efficacy of this graft in improving the integration of soft tissue to bone post RCR.

Methods:

Ten patients were consented to receive the BioEnthesis graft prior to undergoing arthroscopic RCR. Patients received an MRI and patient reported outcomes (PROs) preoperatively and at 6 and 12-months postoperatively. A control cohort was obtained from a previous randomized controlled trial and matched in a 2:1 ratio by sex, tear size, and number of anchors used in the repair. The control cohort had an MRI at 12-months only. Two reviewers (R.D., A.B.Y.) independently graded each MRI according to the Sugaya classification assessing post-operative rotator cuff repair as well as a binomial assessment for the presence of a retear.

Results:

Analysis included 10 patients (7 male, 3 female) receiving the BioEnthesis graft and 20 Control patients (14 male, 6 female). The BioEnthesis cohort was significantly older than the Control cohort (69.7 ± 5.9 vs 56.11 ± 9.4; p<0.001). At 12-months postoperatively, there was a trend in the average Sugaya score graded on MRI favoring the BioEnthesis over the Control cohort (2.28 ± 1.2 vs 3.3 ± 1.09; p=0.054). BioEnthesis patients had a lower rate of retear on 12-month MRI, but this difference was not significant (29% vs 45%; p=0.23). No significant differences were found for PRO’s at any time point. VAS was not assessed for the control group, however, BioEnthesis patients significantly improved from pre-operative to 12-months post-operative (5.0 ± 2.4 to 0.875 ± 0.8; p<0.001). BioEnthesis patients experienced significant strength increases in abduction, scapular plane abduction, and external rotation at 6 and 12-months postoperatively.

Conclusions:

The BioEnthesis graft is a safe graft option that may reduce the risk of retear and help the integration of tendon to bone in arthroscopic RCR.