bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationalising ritual: worship in South Asian Islam between the eighteenth and twentieth centuries
Authors: Zaman Muhammad Qasim 
Published: August 2023

AbstractThis article examines the discussion of core Islamic rituals in the writings of the influential eighteenth-century Sufi, hadith scholar, and jurist Shah Wali Allah of Delhi (d. 1762). It brings out the implications of Wali Allah's sustained concern with demonstrating how divinely mandated rituals serve human interests, not just at the individual but also at the societal and political levels. This aspect of Wali Allah's thought has parallels with how many modernists and Islamists in colonial and post-colonial South Asia have sought to explain Islamic rituals in terms of their social ramifications. But there are some significant differences between them, too, and these help shed further light on Wali Allah's distinctive theory of ritual.
The limits of generality for constitutional design
Authors: Young Andrew T. 
Published: August 2023

AbstractJames Buchanan was a fervent advocate of a non-discriminatory politics. However, he translated his views on constitutional political economy into (de jure) constitutional design in an insufficiently thoughtful way. Simply writing non-discriminatory politics into a Constitution is unlikely to have the desired effect. All Constitutional language is open to interpretation and political entrepreneurs will be ready to push interpretation in their favoured directions. The history of US Constitutional law bears this out. This does not necessarily discount Buchanan's quest for constitutionalized non-discriminatory politics. However, it does mean that it must be tempered by realistic concerns regarding constitutional design. With this in mind, I suggest that focusing on procedural, rather than substantive, Constitutional provisions may be more fruitful.
Institutions and industry-level employment creation: an empirical analysis of the US metro-level data
Authors: Arif Imran 
Published: August 2023

AbstractA growing strand of literature relates pro-market institutions to business and overall employment creation. However, the effects of pro-market institutions on industry-specific employment creation still need to be better understood. Employment creation in some industries may be more sensitive to pro-market institutions. Moreover, if these industries employ a large proportion of the population, the role of local-level institutions becomes more critical for boosting employment creation across industries. Therefore, we disentangle the effects of local-level pro-market institutions on employment creation across nine major industries by using 5-year balanced panel data of 374 US metropolitan areas from 1972 to 2017. Our fixed-effects results indicate that pro-market institutions boost employment creation only in the manufacturing, retail, and construction sectors. Furthermore, our findings reveal that local public policies can benefit or harm local employment creation, depending on the concentration of industries in the area.
Plant growth stages and weather index insurance design
Authors: Zou Jing , Odening Martin , Okhrin Ostap 
Published: August 2023

AbstractGiven the assumption that weather risks affect crop yields, we designed a weather index insurance product for soybean producers in the US state of Illinois. By separating the entire vegetation cycle into four growth stages, we investigate whether the phase-division procedure contributes to weather–yield loss relation estimation and, hence, to basis risk mitigation. Concretely, supposing stage-variant interaction patterns between temperature-based weather index growing degree days and rainfall-based weather index cumulative rainfall, a nonparametric weather–yield loss relation is estimated by a generalized additive model. The model includes penalized B-spline (P-spline) approach based on nonlinear optimal indemnity solutions under the expected utility framework. The P-spline analysis of variance (PS-ANOVA) method is used for efficient estimation through mixed model re-parameterization. The results indicate that the phase-division models significantly outperform the benchmark whole-cycle ones either under quadratic utility or exponential utility, given different levels of risk aversions. Finally, regarding hedging effectiveness, the expected utility ratio between the phase-division contract and the whole-cycle contract, and the percentage changes of mean root square loss and variance of revenues support the proposed phase-division contract.
Probabilistic Landslide Tsunami Estimation in the Makassar Strait, Indonesia, Using Statistical Emulation
Authors: Dignan Jack , Hayward Matthew W. , Salmanidou Dimitra , Heidarzadeh Mohammad , Guillas Serge 
Published: August 2023

AbstractThis paper presents a significant advancement in the understanding of tsunamigenic landslide hazard across the length of the Makassar Strait in Indonesia. We use statistical emulation across the length of the continental slope to conduct a probabilistic assessment of tsunami hazard on a regional scale, across 14 virtual coastal gauges. Focusing on the potential maximum wave amplitudes (distance between the wave crest and the still‐water level) from possible tsunamigenic landslide events, we generate predictions from Gaussian Process emulators fitted to input‐outputs from 50 training scenarios. We show that the most probable maximum wave amplitudes in the majority of gauges are between 1 and 5 m, with the maximum predicted amplitudes reaching values of up to 10 m on the eastern coast, and up to 50 m on the western coast. We also explore the potential use of Gaussian multivariate copulas to sample emulator prediction input values to create a more realistic distribution of volumes along the continental slope. The novel use of statistical emulation across a whole slope enables the probabilistic assessment of tsunami hazard due to landslides on a regional scale. This area is of key interest to Indonesia since the new capital will be established in the East Kalimantan region on the western side of the Makassar Strait.
Whitewater Sound Dependence on Discharge and Wave Configuration at an Adjustable Wave Feature
Authors: Tatum Taylor A. , Anderson Jacob F. , Ronan Timothy J. 
Published: August 2023

AbstractStream acoustics has been proposed as a means of monitoring discharge and wave hazards from outside the stream channel. To better understand the dependence of sound on discharge and wave characteristics, this study analyzes discharge and infrasound data from an artificial wave feature which is adjusted to accommodate daily changes in recreational use and seasonal changes in irrigation demand. Monitorable sound is only observed when discharge exceeds ∼35 m3/s, and even above that threshold the sound‐discharge relationship is non‐linear and inconsistent. When sound is observed, it shows consistent dependence on wave type within a given year, but the direction of this dependence varies among the 3 years studied (2016, 2021, and 2022). These findings support previous research that establishes discharge and stream morphology as relevant controls on stream acoustics and highlights the complex, combined effects of these variables.
Impact of the circadian nuclear receptor REV-ERBα in dorsal raphe 5-HT neurons on social interaction behavior, especially social preference
Authors: Jang Sangwon , Park Inah , Choi Mijung , Kim Jihoon , Yeo Seungeun , Huh Sung-Oh , Choi Ji-Woong , Moon Cheil , Choe Han Kyoung , Choe Youngshik , Kim Kyungjin 
Published: August 2023

AbstractSocial interaction among conspecifics is essential for maintaining adaptive, cooperative, and social behaviors, along with survival among mammals. The 5-hydroxytryptamine (5-HT) neuronal system is an important neurotransmitter system for regulating social behaviors; however, the circadian role of 5-HT in social interaction behaviors is unclear. To investigate whether the circadian nuclear receptor REV-ERBα, a transcriptional repressor of the rate-limiting enzyme tryptophan hydroxylase 2 (Tph2) gene in 5-HT biosynthesis, may affect social interaction behaviors, we generated a conditional knockout (cKO) mouse by targeting Rev-Erbα in dorsal raphe (DR) 5-HT neurons (5-HTDR-specific REV-ERBα cKO) using the CRISPR/Cas9 gene editing system and assayed social behaviors, including social preference and social recognition, with a three-chamber social interaction test at two circadian time (CT) points, i.e., at dawn (CT00) and dusk (CT12). The genetic ablation of Rev-Erbα in DR 5-HTergic neurons caused impaired social interaction behaviors, particularly social preference but not social recognition, with no difference between the two CT points. This deficit of social preference induced by Rev-Erbα in 5-HTDR-specific mice is functionally associated with real-time elevated neuron activity and 5-HT levels at dusk, as determined by fiber-photometry imaging sensors. Moreover, optogenetic inhibition of DR to nucleus accumbens (NAc) 5-HTergic circuit restored the impairment of social preference in 5-HTDR-specific REV-ERBα cKO mice. These results suggest the significance of the circadian regulation of 5-HT levels by REV-ERBα in regulating social interaction behaviors.
PET assessment of acute gastrointestinal graft versus host disease
Authors: Scott Ashleigh P. , Henden Andrea , Kennedy Glen A. , Tey Siok-Keen 
Published: August 2023

AbstractAcute gastrointestinal graft versus host disease (GI-GVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT), and is characterised by severe morbidity, frequent treatment-refractoriness, and high mortality. Early, accurate identification of GI-GVHD could allow for therapeutic interventions to ameliorate its severity, improve response rates and survival; however, standard endoscopic biopsy is inadequately informative in terms of diagnostic sensitivity or outcome prediction. In an era where rapid technological and laboratory advances have dramatically expanded our understanding of GI-GVHD biology and potential therapeutic targets, there is substantial scope for novel investigations that can precisely guide GI-GVHD management. In particular, the combination of tissue-based biomarker assessment (plasma cytokines, faecal microbiome) and molecular imaging by positron emission tomography (PET) offers the potential for non-invasive, real-time in vivo assessment of donor:recipient immune activity within the GI tract for GI-GVHD prediction or diagnosis. In this article, we review the evidence regarding GI-GVHD diagnosis, and examine the potential roles and translational opportunities posed by these novel diagnostic tools, with a focus on the evolving role of PET.
A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer
Authors: Macaulay Valentine M. , Lord Simon , Hussain Syed , Maroto José Pablo , Jones Robert Hugh , Climent Miguel Ángel , Cook Natalie , Lin Chia-Chi , Wang Shian-Shiang , Bianchini Diletta , Bailey Mark , Schlieker Laura , Bogenrieder Thomas , de Bono Johann 
Published: August 2023

Abstract
Background
This multicentre, open-label, Phase Ib/II trial evaluated the insulin-like growth factor (IGF) 1/2 neutralising antibody xentuzumab plus enzalutamide in metastatic castrate-resistant prostate cancer (mCRPC).

Methods
The trial included Phase Ib escalation and expansion parts and a randomised Phase II part versus enzalutamide alone. Primary endpoints in the Phase Ib escalation, Phase Ib expansion and Phase II parts were maximum tolerated dose (MTD), prostate-specific antigen response and investigator-assessed progression-free survival (PFS), respectively. Patients in the Phase Ib escalation and Phase II parts had progressed on/after docetaxel/abiraterone.

Results
In the Phase Ib escalation (n = 10), no dose-limiting toxicities were reported, and xentuzumab 1000 mg weekly plus enzalutamide 160 mg daily (Xe1000 + En160) was defined as the MTD and recommended Phase 2 dose. In the Phase Ib expansion (n = 24), median PFS was 8.2 months, and one patient had a confirmed, long-term response. In Phase II (n = 86), median PFS for the Xe1000 + En160 and En160 arms was 7.4 and 6.2 months, respectively. Subgroup analysis suggested trends towards benefit with Xe1000 + En160 in patients whose tumours had high levels of IGF1 mRNA or PTEN protein. Overall, the combination was well tolerated.

Conclusions
Xentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC.

Clinical trial registration
EudraCT number 2013-004011-41.
Simultaneously discovering the fate and biochemical effects of pharmaceuticals through untargeted metabolomics
Authors: Bowen Tara J. , Southam Andrew D. , Hall Andrew R. , Weber Ralf J. M. , Lloyd Gavin R. , Macdonald Ruth , Wilson Amanda , Pointon Amy , Viant Mark R. 
Published: August 2023

AbstractUntargeted metabolomics is an established approach in toxicology for characterising endogenous metabolic responses to xenobiotic exposure. Detecting the xenobiotic and its biotransformation products as part of the metabolomics analysis provides an opportunity to simultaneously gain deep insights into its fate and metabolism, and to associate the internal relative dose directly with endogenous metabolic responses. This integration of untargeted exposure and response measurements into a single assay has yet to be fully demonstrated. Here we assemble a workflow to discover and analyse pharmaceutical-related measurements from routine untargeted UHPLC-MS metabolomics datasets, derived from in vivo (rat plasma and cardiac tissue, and human plasma) and in vitro (human cardiomyocytes) studies that were principally designed to investigate endogenous metabolic responses to drug exposure. Our findings clearly demonstrate how untargeted metabolomics can discover extensive biotransformation maps, temporally-changing relative systemic exposure, and direct associations of endogenous biochemical responses to the internal dose.
Gain-of-function mutant p53 together with ERG proto-oncogene drive prostate cancer by beta-catenin activation and pyrimidine synthesis
Authors: Ding Donglin , Blee Alexandra M. , Zhang Jianong , Pan Yunqian , Becker Nicole A. , Maher L. James , Jimenez Rafael , Wang Liguo , Huang Haojie 
Published: August 2023

AbstractWhether TMPRSS2-ERG fusion and TP53 gene alteration coordinately promote prostate cancer (PCa) remains unclear. Here we demonstrate that TMPRSS2-ERG fusion and TP53 mutation / deletion co-occur in PCa patient specimens and this co-occurrence accelerates prostatic oncogenesis. p53 gain-of-function (GOF) mutants are now shown to bind to a unique DNA sequence in the CTNNB1 gene promoter and transactivate its expression. ERG and β-Catenin co-occupy sites at pyrimidine synthesis gene (PSG) loci and promote PSG expression, pyrimidine synthesis and PCa growth. β-Catenin inhibition by small molecule inhibitors or oligonucleotide-based PROTAC suppresses TMPRSS2-ERG- and p53 mutant-positive PCa cell growth in vitro and in mice. Our study identifies a gene transactivation function of GOF mutant p53 and reveals β-Catenin as a transcriptional target gene of p53 GOF mutants and a driver and therapeutic target of TMPRSS2-ERG- and p53 GOF mutant-positive PCa.
Droplet-based bisulfite sequencing for high-throughput profiling of single-cell DNA methylomes
Authors: Zhang Qiang , Ma Sai , Liu Zhengzhi , Zhu Bohan , Zhou Zirui , Li Gaoshan , Meana J. Javier , González-Maeso Javier , Lu Chang 
Published: August 2023

AbstractThe genome-wide DNA methylation profile, or DNA methylome, is a critical component of the overall epigenomic landscape that modulates gene activities and cell fate. Single-cell DNA methylomic studies offer unprecedented resolution for detecting and profiling cell subsets based on methylomic features. However, existing single-cell methylomic technologies are based on use of tubes or well plates and these platforms are not easily scalable for handling a large number of single cells. Here we demonstrate a droplet-based microfluidic technology, Drop-BS, to construct single-cell bisulfite sequencing libraries for DNA methylome profiling. Drop-BS takes advantage of the ultrahigh throughput offered by droplet microfluidics to prepare bisulfite sequencing libraries of up to 10,000 single cells within 2 days. We apply the technology to profile mixed cell lines, mouse and human brain tissues to reveal cell type heterogeneity. Drop-BS offers a promising solution for single-cell methylomic studies requiring examination of a large cell population.
Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome
Authors: Seely Savannah M. , Parajuli Narayan P. , De Tarafder Arindam , Ge Xueliang , Sanyal Suparna , Gagnon Matthieu G. 
Published: August 2023

AbstractAminoglycosides are a class of antibiotics that bind to ribosomal RNA and exert pleiotropic effects on ribosome function. Amikacin, the semisynthetic derivative of kanamycin, is commonly used for treating severe infections with multidrug-resistant, aerobic Gram-negative bacteria. Amikacin carries the 4-amino-2-hydroxy butyrate (AHB) moiety at the N1 amino group of the central 2-deoxystreptamine (2-DOS) ring, which may confer amikacin a unique ribosome inhibition profile. Here we use in vitro fast kinetics combined with X-ray crystallography and cryo-EM to dissect the mechanisms of ribosome inhibition by amikacin and the parent compound, kanamycin. Amikacin interferes with tRNA translocation, release factor-mediated peptidyl-tRNA hydrolysis, and ribosome recycling, traits attributed to the additional interactions amikacin makes with the decoding center. The binding site in the large ribosomal subunit proximal to the 3’-end of tRNA in the peptidyl (P) site lays the groundwork for rational design of amikacin derivatives with improved antibacterial properties.
Latent evolution of biofilm formation depends on life-history and genetic background
Authors: Nucci Amandine , Rocha Eduardo P. C. , Rendueles Olaya 
Published: August 2023

AbstractAdaptation to one environment can often generate phenotypic and genotypic changes which impact the future ability of an organism to thrive in other environmental conditions. In the context of host-microbe interactions, biofilm formation can increase survival rates in vivo upon exposure to stresses, like the host’s immune system or antibiotic therapy. However, how the generic process of adaptation impacts the ability to form biofilm and how it may change through time has seldomly been studied. To do so, we used a previous evolution experiment with three strains of theKlebsiella pneumoniaespecies complex, in which we specifically did not select for biofilm formation. We observed that changes in the ability to form biofilm happened very fast at first and afterwards reverted to ancestral levels in many populations. Biofilm changes were associated to changes in population yield and surface polysaccharide production. Genotypically, mutations in the tip adhesin of type III fimbriae (mrkD) or thefimswitch of type I fimbriae were shaped by nutrient availability during evolution, and their impact on biofilm formation was dependent on capsule production. Analyses of natural isolates revealed similar mutations inmrkD, suggesting that such mutations also play an important role in adaptation outside the laboratory. Our work reveals that the latent evolution of biofilm formation, and its temporal dynamics, depend on nutrient availability, the genetic background and other intertwined phenotypic and genotypic changes. Ultimately, it suggests that small differences in the environment can alter an organism’s fate in more complex niches like the host.
Soliton pulse pairs at multiple colours in normal dispersion microresonators
Authors: Yuan Zhiquan , Gao Maodong , Yu Yan , Wang Heming , Jin Warren , Ji Qing-Xin , Feshali Avi , Paniccia Mario , Bowers John , Vahala Kerry 
Published: August 2023

AbstractSoliton microcombs are helping to advance the miniaturization of a range of comb systems. These combs mode lock through the formation of short temporal pulses in anomalous dispersion resonators. Here, a new microcomb is demonstrated that mode locks through the formation of pulse pairs in coupled normal dispersion resonators. Unlike conventional microcombs, pulses in this system cannot exist alone, and instead phase lock in pairs wherein pulses in each pair feature different optical spectra. The pairwise mode-locking modality extends to multiple pulse pairs and beyond two rings, and it greatly constrains mode-locking states. Two- (bipartite) and three-ring (tripartite) states containing many pulse pairs are demonstrated, including crystal states. Pulse pairs can also form at recurring spectral windows. We obtained the results using an ultra-low-loss Si3N4 platform that has not previously produced bright solitons on account of its inherent normal dispersion. The ability to generate multicolour pulse pairs over multiple rings is an important new feature for microcombs. It can extend the concept of all-optical soliton buffers and memories to multiple storage rings that multiplex pulses with respect to soliton colour and that are spatially addressable. The results also suggest a new platform for the study of topological photonics and quantum combs.
Design of a mucin-selective protease for targeted degradation of cancer-associated mucins
Authors: Pedram Kayvon , Shon D. Judy , Tender Gabrielle S. , Mantuano Natalia R. , Northey Jason J. , Metcalf Kevin J. , Wisnovsky Simon P. , Riley Nicholas M. , Forcina Giovanni C. , Malaker Stacy A. , Kuo Angel , George Benson M. , Miller Caitlyn L. , Casey Kerriann M. , Vilches-Moure José G. , Ferracane Michael J. , Weaver Valerie M. , Läubli Heinz , Bertozzi Carolyn R. 
Published: August 2023

AbstractTargeted protein degradation is an emerging strategy for the elimination of classically undruggable proteins. Here, to expand the landscape of targetable substrates, we designed degraders that achieve substrate selectivity via recognition of a discrete peptide and glycan motif and achieve cell-type selectivity via antigen-driven cell-surface binding. We applied this approach to mucins, O-glycosylated proteins that drive cancer progression through biophysical and immunological mechanisms. Engineering of a bacterial mucin-selective protease yielded a variant for fusion to a cancer antigen-binding nanobody. The resulting conjugate selectively degraded mucins on cancer cells, promoted cell death in culture models of mucin-driven growth and survival, and reduced tumor growth in mouse models of breast cancer progression. This work establishes a blueprint for the development of biologics that degrade specific protein glycoforms on target cells.
Somatic mutations in facial skin from countries of contrasting skin cancer risk
Authors: King Charlotte , Fowler Joanna C. , Abnizova Irina , Sood Roshan K. , Hall Michael W. J. , Szeverényi Ildikó , Tham Muly , Huang Jingxiang , Young Stephanie Ming , Hall Benjamin A. , Birgitte Lane E. , Jones Philip H. 
Published: August 2023

AbstractThe incidence of keratinocyte cancer (basal cell and squamous cell carcinomas of the skin) is 17-fold lower in Singapore than the UK1–3, despite Singapore receiving 2–3 times more ultraviolet (UV) radiation4,5. Aging skin contains somatic mutant clones from which such cancers develop6,7. We hypothesized that differences in keratinocyte cancer incidence may be reflected in the normal skin mutational landscape. Here we show that, compared to Singapore, aging facial skin from populations in the UK has a fourfold greater mutational burden, a predominant UV mutational signature, increased copy number aberrations and increased mutant TP53 selection. These features are shared by keratinocyte cancers from high-incidence and low-incidence populations8–13. In Singaporean skin, most mutations result from cell-intrinsic processes; mutant NOTCH1 and NOTCH2 are more strongly selected than in the UK. Aging skin in a high-incidence country has multiple features convergent with cancer that are not found in a low-risk country. These differences may reflect germline variation in UV-protective genes.