bluuebunny/crossref_metadata_2025_split huggingface dataset:
“We Are Happy Here”: Creating Communist Cuba and the Mariel Crisis of 1980
Authors: Guerra Lillian 
Published: May 2024

AbstractAt a time when Cuban immigrants are seeking political asylum at historically unprecedented rates, most press and scholarly accounts consistently mirror earlier portrayals of Cubans’ mass exodus from the island in one key aspect: they ascribe to refugees a primarily economic reason for their decision to leave and offer little discussion of political factors. To illuminate the need for such analysis, this article examines the Mariel Boatlift of 1980, when approximately 125,000 Cubans, most of them thirty years old or younger, left Cuba. No other exodus of Cubans was more demonized than the Mariel, both by Cuba’s supporters and leadership and by exile opponents of the communist state. Exploring how the intensification of ideological criteria for inclusion in the Cuban Revolution undermined the quality of Cubans’ liberation under socialism prior to Mariel, this article explores state policies and the deep politicization of everyday life and identity. Key political factors explain many young people’s alienation and the degree to which the Cuban state sanctioned and directed extreme measures of repression to discredit those who wanted to leave as lazy, sexually degenerate escoria (human trash).
Reduced-resolution beamforming: Lowering the computational cost for pulsar and technosignature surveys
Authors: Price D.C. 
Published: May 2024

AbstractIn radio astronomy, the science output of a telescope is often limited by computational resources. This is especially true for transient and technosignature surveys that need to search high-resolution data across a large parameter space. The tremendous data volumes produced by modern radio array telescopes exacerbate these processing challenges. Here, we introduce a ‘reduced-resolution’ beamforming approach to alleviate downstream processing requirements. Our approach, based on post-correlation beamforming, allows sensitivity to be traded against the number of beams needed to cover a given survey area. Using the MeerKAT and Murchison Widefield Array telescopes as examples, we show that survey speed can be vastly increased, and downstream signal processing requirements vastly decreased, if a moderate sacrifice to sensitivity is allowed. We show the reduced-resolution beamforming technique is intimately related to standard techniques used in synthesis imaging. We suggest that reduced-resolution beamforming should be considered to ease data processing challenges in current and planned searches; further, reduced-resolution beamforming may provide a path to computationally expensive search strategies previously considered infeasible.
STRAIGHT TALK ABOUT CURVED HORNS AND GAY MARRIAGE: A NEW READING OF JUVENAL'S SECOND SATIRE
Authors: Herz Zachary 
Published: May 2024

AbstractThis article argues that one of our only pieces of evidence for Roman marriage between cinaedi, Juvenal's second satire, has been consistently misread and in fact describes a marriage between a cinaedus and a sex worker. It begins by providing the context for the passage in question and its traditional reading, and then demonstrates that the critical phrase siue hic recto cantauerat aere refers to financial, not erotic, exchanges. The article finally discusses the implications of this correction, which are far more substantial than one might expect for a contentious ablative.
Overseas Trade and War. Reconstructing a Late Eighteenth-Century East India Company Voyage to Asia Between Routine and Unpredictability
Authors: Chiocchetti Filippo 
Published: May 2024

AbstractThe role played by the East India Company in European expansion in early modern Asia is of such importance that it has generated a large body of scholarly literature. However, the logbooks of the East Indiamen, compiled by their captains, are largely overlooked as a primary source for the history of navigation, despite the wealth of information such firsthand, “from below” documents could provide about those voyages. As part of the Global Sea Routes (GSR) project, this essay analyses the voyage of theNassau(1781–85) along four main themes: the peculiarities of navigation during the Age of Sail, when the duration of a voyage was difficult to predict and subject to a range of possible accidents; the concrete reality of life on board, oscillating between the various activities of the crew and the episodes of desertion and insubordination that broke its daily routine; her military deployment, as theNassauwas directly involved in operations related to the Second Anglo-Mysore War; and, finally, her commercial activities, from the port cities of India to the seas of China.
Spatial and Temporal Changes in Nutrient Source Contribution in a Lowland Catchment Within the Baltic Sea Region Under Climate Change Scenarios
Authors: Bojanowski Damian , Orlińska‐Woźniak Paulina , Wilk Paweł , Jakusik Ewa , Szalińska Ewa 
Published: May 2024

AbstractCurrently, climate change is considered as an important factor affecting nutrient loads introduced through riverine systems into the Baltic Sea. Although the prospect of a large increase in pollution has long seemed very real, it still does not translate into planning of effective remedial actions. One of the factors limiting the development of such activities is the scale of simulations, focusing generally on catchment outlet profiles. To fill this gap and enable a step forward in understanding responses toward future predictions in a higher resolution scale (subcatchment), we assessed nutrient load contribution using calculation profiles localized along a main watercourse and its tributaries. To track spatial and seasonal changes of total nitrogen and phosphorus for the Wełna River (central Poland), we used climate change data and the SWAT model. Having at our disposal a catchment model with a good performance we could follow not only total load changes in particular subcatchments, but also track localization of the pollution sources and their direct impact on load estimations. Our results showed an increase of the loads, especially from the agricultural land use type, up to 34% for TN and 85% for TP, in the most extreme scenario. Moreover, forest areas have been noted as highly reactive to climate change, and through their localisation are able to distinctly alter nutrient outflow. Finally, the contribution of urban areas should be further investigated since the dynamics of nitrogen and phosphorus release from impervious surfaces is noticeably different here than from the other diffuse sources.
Disambiguating Concepts of Fairness in Stormwater Management: A Review of Economic Efficiency and Equity
Authors: Arik Aida D. 
Published: May 2024

AbstractTo confront the converging challenges of failing infrastructure, climate change, degraded water quality, and fewer undeveloped lands, many municipalities are establishing stormwater utilities (SWUs) to allocate a dedicated funding source to stormwater management (SWM) services. As a public service, creating a “fair” SWU by defining collective values that reflect community and municipal needs is crucial. However, the prevalent professional discourse surrounding SWUs often conflates “equity” with “economic efficiency” when they are two theoretically separate concepts, which obscure concerns raised by service beneficiaries. This paper unpacks ideas of fairness based on a systematic literature review that frames SWM financing in terms of economic efficiency and SWM services in terms of distributional, procedural, and structural equity. The distinction of which is important to set appropriate expectations between SWUs and beneficiaries.
Predicting survival in patients with myelodysplastic/myeloproliferative neoplasms with SF3B1 mutation and thrombocytosis
Authors: Li Fuhui , Qin Tiejun , Li Bing , Qu Shiqiang , Pan Lijuan , Zhang Peihong , Sun Qi , Cai Wenyu , Gao Qingyan , Jiao Meng , Li Junjie , Ai Xiaofei , Ma Jiao , Gale Robert Peter , Xu Zefeng , Xiao Zhijian 
Published: May 2024

AbstractWe investigated data from 180 consecutive patients with myelodysplastic/myeloproliferative neoplasms with SF3B1 mutation and thrombocytosis (MDS/MPN-SF3B1-T) who were diagnosed according to the 2022 World Health Organization (WHO) classification of myeloid neoplasms to identify covariates associated with survival. At a median follow-up of 48 months (95% confidence interval [CI] 35–61 months), the median survival was 69 months (95% CI 59–79 months). Patients with bone marrow ring sideroblasts (RS) < 15% had shorter median overall survival (OS) than did those with bone marrow RS ≥ 15% (41 months [95% CI 32–50 months] versus 76 months [95% CI 59–93 months]; P < 0.001). According to the univariable analyses of OS, age ≥ 65 years (P < 0.001), hemoglobin concentration (Hb) < 80 g/L (P = 0.090), platelet count (PLT) ≥ 800 × 10E + 9/L (P = 0.087), bone marrow RS < 15% (P < 0.001), the Revised International Prognostic Scoring System (IPSS-R) cytogenetic category intermediate/poor/very poor (P = 0.005), SETBP1 mutation (P = 0.061) and SRSF2 mutation (P < 0.001) were associated with poor survival. Based on variables selected from univariable analyses, two separate survival prediction models, a clinical survival model, and a clinical-molecular survival model, were developed using multivariable analyses with the minimum value of the Akaike information criterion (AIC) to specifically predict outcomes in patients with MDS/MPN-SF3B1-T according to the 2022 WHO classification.
CRISPR-dCas13d-based deep screening of proximal and distal splicing-regulatory elements
Authors: Recinos Yocelyn , Ustianenko Dmytro , Yeh Yow-Tyng , Wang Xiaojian , Jacko Martin , Yesantharao Lekha V. , Wu Qiyang , Zhang Chaolin 
Published: May 2024

AbstractPre-mRNA splicing, a key process in gene expression, can be therapeutically modulated using various drug modalities, including antisense oligonucleotides (ASOs). However, determining promising targets is hampered by the challenge of systematically mapping splicing-regulatory elements (SREs) in their native sequence context. Here, we use the catalytically inactive CRISPR-RfxCas13d RNA-targeting system (dCas13d/gRNA) as a programmable platform to bind SREs and modulate splicing by competing against endogenous splicing factors. SpliceRUSH, a high-throughput screening method, was developed to map SREs in any gene of interest using a lentivirus gRNA library that tiles the genetic region, including distal intronic sequences. When applied to SMN2, a therapeutic target for spinal muscular atrophy, SpliceRUSH robustly identifies not only known SREs but also a previously unknown distal intronic SRE, which can be targeted to alter exon 7 splicing using either dCas13d/gRNA or ASOs. This technology enables a deeper understanding of splicing regulation with applications for RNA-based drug discovery.
Characterizing the mechanism of action for mRNA therapeutics for the treatment of propionic acidemia, methylmalonic acidemia, and phenylketonuria
Authors: Baek Rena , Coughlan Kimberly , Jiang Lei , Liang Min , Ci Lei , Singh Harkewal , Zhang Hannah , Kaushal Neeraj , Rajlic Ivana Liric , Van Linh , Dimen Rain , Cavedon Alexander , Yin Ling , Rice Lisa , Frassetto Andrea , Guey Lin , Finn Patrick , Martini Paolo G. V. 
Published: May 2024

AbstractMessenger RNA (mRNA) therapeutics delivered via lipid nanoparticles hold the potential to treat metabolic diseases caused by protein deficiency, including propionic acidemia (PA), methylmalonic acidemia (MMA), and phenylketonuria (PKU). Herein we report results from multiple independent preclinical studies of mRNA-3927 (an investigational treatment for PA), mRNA-3705 (an investigational treatment for MMA), and mRNA-3210 (an investigational treatment for PKU) in murine models of each disease. All 3 mRNA therapeutics exhibited pharmacokinetic/pharmacodynamic (PK/PD) responses in their respective murine model by driving mRNA, protein, and/or protein activity responses, as well as by decreasing levels of the relevant biomarker(s) when compared to control-treated animals. These preclinical data were then used to develop translational PK/PD models, which were scaled allometrically to humans to predict starting doses for first-in-human clinical studies for each disease. The predicted first-in-human doses for mRNA-3927, mRNA-3705, and mRNA-3210 were determined to be 0.3, 0.1, and 0.4 mg/kg, respectively.
FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma
Authors: Zhen Yuanli , Liu Kai , Shi Lei , Shah Simran , Xu Qin , Ellis Haley , Balasooriya Eranga R. , Kreuzer Johannes , Morris Robert , Baldwin Albert S. , Juric Dejan , Haas Wilhelm , Bardeesy Nabeel 
Published: May 2024

AbstractGenomic alterations that activate Fibroblast Growth Factor Receptor 2 (FGFR2) are common in intrahepatic cholangiocarcinoma (ICC) and confer sensitivity to FGFR inhibition. However, the depth and duration of response is often limited. Here, we conduct integrative transcriptomics, metabolomics, and phosphoproteomics analysis of patient-derived models to define pathways downstream of oncogenic FGFR2 signaling that fuel ICC growth and to uncover compensatory mechanisms associated with pathway inhibition. We find that FGFR2-mediated activation of Nuclear factor-κB (NF-κB) maintains a highly glycolytic phenotype. Conversely, FGFR inhibition blocks glucose uptake and glycolysis while inciting adaptive changes, including switching fuel source utilization favoring fatty acid oxidation and increasing mitochondrial fusion and autophagy. Accordingly, FGFR inhibitor efficacy is potentiated by combined mitochondrial targeting, an effect enhanced in xenograft models by intermittent fasting. Thus, we show that oncogenic FGFR2 signaling drives NF-κB-dependent glycolysis in ICC and that metabolic reprogramming in response to FGFR inhibition confers new targetable vulnerabilities.
Pharmacological inhibition of α-synuclein aggregation within liquid condensates
Authors: Dada Samuel T. , Toprakcioglu Zenon , Cali Mariana P. , Röntgen Alexander , Hardenberg Maarten C. , Morris Owen M. , Mrugalla Lena K. , Knowles Tuomas P. J. , Vendruscolo Michele 
Published: May 2024

AbstractAggregated forms of α-synuclein constitute the major component of Lewy bodies, the proteinaceous aggregates characteristic of Parkinson’s disease. Emerging evidence suggests that α-synuclein aggregation may occur within liquid condensates formed through phase separation. This mechanism of aggregation creates new challenges and opportunities for drug discovery for Parkinson’s disease, which is otherwise still incurable. Here we show that the condensation-driven aggregation pathway of α-synuclein can be inhibited using small molecules. We report that the aminosterol claramine stabilizes α-synuclein condensates and inhibits α-synuclein aggregation within the condensates both in vitro and in a Caenorhabditis elegans model of Parkinson’s disease. By using a chemical kinetics approach, we show that the mechanism of action of claramine is to inhibit primary nucleation within the condensates. These results illustrate a possible therapeutic route based on the inhibition of protein aggregation within condensates, a phenomenon likely to be relevant in other neurodegenerative disorders.
Compensating affected parties necessary for rapid coal phase-out but expensive if extended to major emitters
Authors: Nacke Lola , Vinichenko Vadim , Cherp Aleh , Jakhmola Avi , Jewell Jessica 
Published: May 2024

AbstractCoal power phase-out is critical for climate mitigation, yet it harms workers, companies, and coal-dependent regions. We find that more than half of countries that pledge coal phase-out have “just transition” policies which compensate these actors. Compensation is larger in countries with more ambitious coal phase-out pledges and most commonly directed to national and regional governments or companies, with a small share going directly to workers. Globally, compensation amounts to over $200 billion (uncertainty 163-258), about half of which is funded through international schemes, mostly through Just Energy Transition Partnerships and the European Union Just Transition Fund. If similar transfers are extended to China and India to phase out coal in line with the Paris temperature targets, compensation flows could become larger than current international climate financing. Our findings highlight that the socio-political acceptance of coal phase-out has a tangible economic component which should be factored into assessing the feasibility of achieving climate targets.
Cardiac function is regulated by the sodium-dependent inhibition of the sodium-calcium exchanger NCX1
Authors: Scranton Kyle , John Scott , Angelini Marina , Steccanella Federica , Umar Soban , Zhang Rui , Goldhaber Joshua I. , Olcese Riccardo , Ottolia Michela 
Published: May 2024

AbstractThe Na+-Ca2+ exchanger (NCX1) is the dominant Ca2+ extrusion mechanism in cardiac myocytes. NCX1 activity is inhibited by intracellular Na+ via a process known as Na+-dependent inactivation. A central question is whether this inactivation plays a physiological role in heart function. Using CRISPR/Cas9, we inserted the K229Q mutation in the gene (Slc8a1) encoding for NCX1. This mutation removes the Na+-dependent inactivation while preserving transport properties and other allosteric regulations. NCX1 mRNA levels, protein expression, and protein localization are unchanged in K229Q male mice. However, they exhibit reduced left ventricular ejection fraction and fractional shortening, while displaying a prolonged QT interval. K229Q ventricular myocytes show enhanced NCX1 activity, resulting in action potential prolongation, higher incidence of aberrant action potentials, a faster decline of Ca2+ transients, and depressed cell shortening. The results demonstrate that NCX1 Na+-dependent inactivation plays an essential role in heart function by affecting both cardiac excitability and contractility.
Quantum fluctuations lead to glassy electron dynamics in the good metal regime of electron doped KTaO3
Authors: Ojha Shashank Kumar , Hazra Sankalpa , Bera Surajit , Gogoi Sanat Kumar , Mandal Prithwijit , Maity Jyotirmay , Gloskovskii Andrei , Schlueter Christoph , Karmakar Smarajit , Jain Manish , Banerjee Sumilan , Gopalan Venkatraman , Middey Srimanta 
Published: May 2024

AbstractOne of the central challenges in condensed matter physics is to comprehend systems that have strong disorder and strong interactions. In the strongly localized regime, their subtle competition leads to glassy electron dynamics which ceases to exist well before the insulator-to-metal transition is approached as a function of doping. Here, we report on the discovery of glassy electron dynamics deep inside the good metal regime of an electron-doped quantum paraelectric system: KTaO3. We reveal that upon excitation of electrons from defect states to the conduction band, the excess injected carriers in the conduction band relax in a stretched exponential manner with a large relaxation time, and the system evinces simple aging phenomena—a telltale sign of glassy dynamics. Most significantly, we observe a critical slowing down of carrier dynamics below 35 K, concomitant with the onset of quantum paraelectricity in the undoped KTaO3. Our combined investigation using second harmonic generation technique, density functional theory and phenomenological modeling demonstrates quantum fluctuation-stabilized soft polar modes as the impetus for the glassy behavior. This study addresses one of the most fundamental questions regarding the potential promotion of glassiness by quantum fluctuations and opens a route for exploring glassy dynamics of electrons in a well-delocalized regime.
Specific exercise patterns generate an epigenetic molecular memory window that drives long-term memory formation and identifies ACVR1C as a bidirectional regulator of memory in mice
Authors: Keiser Ashley A. , Dong Tri N. , Kramár Enikö A. , Butler Christopher W. , Chen Siwei , Matheos Dina P. , Rounds Jacob S. , Rodriguez Alyssa , Beardwood Joy H. , Augustynski Agatha S. , Al-Shammari Ameer , Alaghband Yasaman , Alizo Vera Vanessa , Berchtold Nicole C. , Shanur Sharmin , Baldi Pierre , Cotman Carl W. , Wood Marcelo A. 
Published: May 2024

AbstractExercise has beneficial effects on cognition throughout the lifespan. Here, we demonstrate that specific exercise patterns transform insufficient, subthreshold training into long-term memory in mice. Our findings reveal a potential molecular memory window such that subthreshold training within this window enables long-term memory formation. We performed RNA-seq on dorsal hippocampus and identify genes whose expression correlate with conditions in which exercise enables long-term memory formation. Among these genes we found Acvr1c, a member of the TGF ß family. We find that exercise, in any amount, alleviates epigenetic repression at the Acvr1c promoter during consolidation. Additionally, we find that ACVR1C can bidirectionally regulate synaptic plasticity and long-term memory in mice. Furthermore, Acvr1c expression is impaired in the aging human and mouse brain, as well as in the 5xFAD mouse model, and over-expression of Acvr1c enables learning and facilitates plasticity in mice. These data suggest that promoting ACVR1C may protect against cognitive impairment.
Harnessing noncanonical crRNA for highly efficient genome editing
Authors: Xun Guanhua , Zhu Zhixin , Singh Nilmani , Lu Jingxia , Jain Piyush K. , Zhao Huimin 
Published: May 2024

AbstractThe CRISPR-Cas12a system is more advantageous than the widely used CRISPR-Cas9 system in terms of specificity and multiplexibility. However, its on-target editing efficiency is typically much lower than that of the CRISPR-Cas9 system. Here we improved its on-target editing efficiency by simply incorporating 2-aminoadenine (base Z, which alters canonical Watson-Crick base pairing) into the crRNA to increase the binding affinity between crRNA and its complementary DNA target. The resulting CRISPR-Cas12a (named zCRISPR-Cas12a thereafter) shows an on-target editing efficiency comparable to that of the CRISPR-Cas9 system but with much lower off-target effects than the CRISPR-Cas9 system in mammalian cells. In addition, zCRISPR-Cas12a can be used for precise gene knock-in and highly efficient multiplex genome editing. Overall, the zCRISPR-Cas12a system is superior to the CRISPR-Cas9 system, and our simple crRNA engineering strategy may be extended to other CRISPR-Cas family members as well as their derivatives.
tauFisher predicts circadian time from a single sample of bulk and single-cell pseudobulk transcriptomic data
Authors: Duan Junyan , Ngo Michelle N. , Karri Satya Swaroop , Tsoi Lam C. , Gudjonsson Johann E. , Shahbaba Babak , Lowengrub John , Andersen Bogi 
Published: May 2024

AbstractAs the circadian clock regulates fundamental biological processes, disrupted clocks are often observed in patients and diseased tissues. Determining the circadian time of the patient or the tissue of focus is essential in circadian medicine and research. Here we present tauFisher, a computational pipeline that accurately predicts circadian time from a single transcriptomic sample by finding correlations between rhythmic genes within the sample. We demonstrate tauFisher’s performance in adding timestamps to both bulk and single-cell transcriptomic samples collected from multiple tissue types and experimental settings. Application of tauFisher at a cell-type level in a single-cell RNAseq dataset collected from mouse dermal skin implies that greater circadian phase heterogeneity may explain the dampened rhythm of collective core clock gene expression in dermal immune cells compared to dermal fibroblasts. Given its robustness and generalizability across assay platforms, experimental setups, and tissue types, as well as its potential application in single-cell RNAseq data analysis, tauFisher is a promising tool that facilitates circadian medicine and research.