bluuebunny/crossref_metadata_2025 huggingface dataset:
Thinking with Paul Kramer's “Power and Connection”
Authors: Von Eschen Penny
Published: April 2024

I am delighted to have an opportunity to reflect on Paul Kramer's rich and highly influential “Power and Connection: Imperial Histories of the United States in the World.” Since its publication in 2011, “Power and Connection” has been a cornerstone of my graduate U.S. in the World classes and has been invoked in every graduate qualifying exam. The essay has had a direct and indirect influence on the wave of innovative scholarship that has been produced in the past decade. I first want to note some of the essay's important interventions. Then, rather than attempting to extend or update Kramer's extensive historiographical review, I want to think with “Power and Connection” by taking up two of Kramer's suggestions and discussions. First, I take up his suggestion to think about imperial power through a Gramscian frame of domination and consent, arguing that the concept of hegemonic struggle is critical for thinking about power within empires and shifts in global imperial formations. Second, I engage Kramer's discussion of the relationship between imperial and transnational histories, arguing that scholars need to consider transnationalism as a highly specific and contingent political formation, as well as an analytic category and sometimes actors' category.
Reason of State, Stände, and Estates in German and English Exchanges over the Crisis in the Palatinate, 1618–24
Authors: Hutchinson Mark A.
Published: April 2024

When, in 1619, Frederick V of the Palatinate accepted the crown of Bohemia, he justified his action, which challenged the authority of Emperor Ferdinand II and precipitated the Thirty Years’ War, by the need to uphold the public order, rights, and responsibilities connected to the estates of the empire. English engagements with the German vocabulary of estates drew upon the concept of reason of state—those amoral political calculations needed to maintain a group's estate, or standing. The article examines the significance of these differences in a vocabulary of estates and state.
EURIPIDES, TROADES 95–7: IS SOMETHING MISSING?
Authors: Kovacs David
Published: April 2024

This paper raises objections to the constitution of these lines in the OCT. The lines are gnomic but they generalize based on an actual sequence of events just described and should contain an allusion to the offence that will cause the Greeks to perish, the outrage against Athena's temple. This, it is argued, stood in a lacuna best marked after 95. The article has three theses: (1) sacking ‘cities, temples, and tombs’ is implausible because the latter two are parts of the first; (2) plundering tombs refers to nothing in the play, nor was this thought of as an offence against the gods; (3) 96–7 do not refer to the offence that causes the fool's death but are a description of his success, the destruction of the hated enemy population. That success stands in ironic contrast with his subsequent death.
TWO NOTES ON AURELIUS VICTOR'S LIBER DE CAESARIBVS (10.5 LAVTVSQVE AND 13.3 SATISQVE)
Authors: Rudoni Elia
Published: April 2024

At Aur. Vict. Caes. 10.5, the reading lautus should be retained; -que is a dittography and should be deleted. At 13.3, satis should be emended into sagatis. This article also provides a brief analysis of Victor's references to clothing and attempts to explain why he comments on the Dacian costume at 13.3, the only ethnographic reference to clothing in the entire work.
Occult neck metastasis in salvage laryngectomy: a road map for super-selective neck dissection
Authors: Youssef Ahmed , Milton Austin , Patel Rusha , Mhawej Rachad , Vasan Nilesh , Krempl Greg
Published: April 2024

Objective

This study aimed to solve the debate over the role and extent of neck dissection to treat any occult nodal metastasis in patients undergoing salvage laryngectomy for recurrent and/or residual squamous cell carcinoma of larynx.

Methods

This was a retrospective study over a time frame of 6 years (2016–2022) of 74 patients who underwent bilateral neck dissection and salvage laryngectomy for recurrent or persistent disease with N0 neck. We calculated the incidence of occult nodal metastasis in ipsilateral and contralateral neck.

Results

Incidence of ipsilateral neck disease was calculated as 8.11 per cent and it was 0 per cent in contralateral neck. Regarding ipsilateral nodal level distribution, level II was the highest at 6.76 per cent, followed by level III at 5.41 per cent. There was 0 per cent metastasis in levels IV and IIb.

Conclusion

In patients undergoing salvage laryngectomy with N0 neck, ipsilateral super selective neck dissection is considered a convenient and oncologically safe option to treat the neck.
“There Can Be No Agreement to Take up Arms against the Turks Unless We First Restore the Empire”: The Fall of Constantinople and the Rise of a New Political Dynamic in the Holy Roman Empire, 1453–1467
Authors: Hardy Duncan
Published: April 2024

While the Europe-wide cultural impact of the fall of Constantinople to Sultan Mehmed II is well known, its political reverberations in the Holy Roman Empire have received comparatively little attention. This article argues that the events of 1453 inaugurated a new dynamic in the empire that facilitated the polity's consolidation and the creation of new collective institutions within it long before Maximilian I (1486–1519), whose reign is often presented as a constitutional turning point. Some prince-electors had been calling for more effective peace-keeping and judicial institutions for decades before 1453 but lacked the leverage to compel kings and emperors of the Romans to accept political change on their terms. The fall of Constantinople provided a focal point for these negotiations: in return for promising to support an anti-Ottoman crusade, the reformists were able to force a compromise on new peace-keeping legislation at the diets of the 1450s and 1460s. This compromise was catalyzed by public pressure. There was a widely held expectation that leading imperial protagonists should fulfill this mission to defend Christendom, manifested in orations, diplomatic missives, poetry and songs, plays, and early printed pamphlets produced within and for a range of German-speaking public spheres.
Understanding alcohol use and alcohol use disorders from a developmental psychopathology perspective: Research advances, challenges, and future directions
Authors: Chassin Laurie , Sher Kenneth J.
Published: April 2024

As part of the special issue of Development and Psychopathology honoring the remarkable contributions of Dr Dante Cicchetti, the current paper attempts to describe the recent contributions that a developmental psychopathology perspective has made in understanding the development of alcohol use and alcohol-related problems over the lifespan. The paper also identifies some of the future challenges and research directions. Because the scope of this task far exceeds the confines of a journal length article this paper does not attempt a comprehensive review. Rather, it builds on an earlier review and commentary that was published in Development and Psychopathology in 2013, with a similar goal.)Building on that work and updating its conclusions and suggestions for future directions, the current paper emphasizes findings from the research areas that were identified for further study in 2013 and the findings that have been published since that time.
Impulsivity profiles across five harmonized longitudinal childhood preventive interventions and associations with adult outcomes
Authors: Goulter Natalie , Amin-Esmaeili Masoumeh , Susukida Ryoko , Kush Joseph M. , Godwin Jennifer , Masyn Katherine , McMahon Robert J. , Eddy J. Mark , Ialongo Nicholas S. , Tolan Patrick H. ,   Conduct Problems Prevention Research Group, Wilcox Holly C. , Musci Rashelle J.
Published: April 2024

This study aimed to parse between-person heterogeneity in growth of impulsivity across childhood and adolescence among participants enrolled in five childhood preventive intervention trials targeting conduct problems. In addition, we aimed to test profile membership in relation to adult psychopathologies. Measurement items representing impulsive behavior across grades 2, 4, 5, 7, 8, and 10, and aggression, substance use, suicidal ideation/attempts, and anxiety/depression in adulthood were integrated from the five trials (N = 4,975). We applied latent class growth analysis to this sample, as well as samples separated into nonintervention (n = 2,492) and intervention (n = 2,483) participants. Across all samples, profiles were characterized by high, moderate, low, and low-increasing impulsive levels. Regarding adult outcomes, in all samples, the high, moderate, and low profiles endorsed greater levels of aggression compared to the low-increasing profile. There were nuanced differences across samples and profiles on suicidal ideation/attempts and anxiety/depression. Across samples, there were no significant differences between profiles on substance use. Overall, our study helps to inform understanding of the developmental course and prognosis of impulsivity, as well as adding to collaborative efforts linking data across multiple studies to better inform understanding of developmental processes.
Female rats consuming an iron and omega-3 fatty acid deficient diet preconception require combined iron and omega-3 fatty acid supplementation for the prevention of bone impairments in offspring
Authors: Venter Estelle , Zandberg Lizelle , Venter Philip vZ. , Smuts Cornelius M. , Kruger Herculina S. , Baumgartner Jeannine
Published: April 2024

We previously showed in rats that pre- and postnatal deficiencies in iron and omega-3 (n-3) fatty acids can impair bone development, with additive and potentially irreversible effects when combined. This study aimed to investigate, in female rats consuming a combined iron and n-3 fatty acid deficient (ID + n-3 FAD) diet preconception, whether supplementation with iron and docosahexaenoic/eicosapentaenoic acid (DHA/EPA), alone and in combination, can prevent bone impairments in offspring. Using a 2 × 2 factorial design, female Wistar rats consuming an ID + n-3 FAD diet preconception were randomised to receive an: 1) iron supplemented (Fe + n-3 FAD), 2) DHA/EPA supplemented (ID + DHA/EPA), 3) Fe + DHA/EPA, or 4) ID + n-3 FAD diet from gestational day 10 throughout pregnancy and lactation. Post-weaning, offspring (n = 24/group; male:female = 1:1) remained on the respective experimental diets for three weeks until postnatal day 42–45. Offspring born to female rats consuming a control diet preconception and an Fe+DHA/EPA diet throughout pregnancy and lactation served as non-deficient reference group (Control+Fe+DHA/EPA). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and bone strength using three-point bending tests. Only offspring in the Fe+DHA/EPA group had significantly higher spine and femur BMD, and higher femur stiffness than offspring in the ID + n-3 FAD group, and had similar spine BMD and femur stiffness as the Control + Fe + DHA/EPA group. Offspring in the Fe + DHA/EPA group further had significantly higher femur strength (ultimate load) than the other experimental groups, and a similar femur strength as the Control + Fe + DHA/EPA group. This study shows that only combined iron and DHA/EPA supplementation can prevent bone impairments in offspring of female rats consuming an iron and n-3 FA deficient diet preconception.
Guiding Fuzzy Cognitive Mapping With Structured Decision Making to Inform Complex Natural Resource Management Problems in Waiʻanae Hawaiʻi
Authors: Cleveland Rachael , Trauernicht Clay , Bremer Leah , Pickett Elizabeth , Oleson Kirsten L. L.
Published: April 2024

Fire is one example of a larger class of wicked environmental management problems that require community‐based management for long‐term success. This study aimed to support participatory decision making in a data poor and complex system by using Fuzzy Cognitive Mapping (FCM) within the decision‐making framework Structured Decision Making (SDM) to develop a community‐based wildfire management plan in partnership with a local group in Wai‘anae Hawaiʻi. SDM is an organized process to create and evaluate decisions that can clarify trade‐offs and increase transparency. FCM is a semi‐quantitative method to describe system relationships that can handle low data and high uncertainty. We used SDM to define the problem, articulate community concerns related to wildfire, and identify management actions. We then used FCM to model how these actions affected valued ecosystem services and other stakeholder‐identified objectives. Modeling results highlighted the trade‐offs across three valued ecosystem services from three community‐led wildfire management actions. We found that native species outplanting was the most beneficial action to each of the three valued ecosystem services. Through this participatory research, we conclude that the SDM and FCM pairing provided an inclusive and cost‐effective way to engage with a specific wildfire management context, and that the process effectively engaged stakeholders while tackling uncertainty. This process also aided consensus‐building and group member communication. This pairing can be used to aid community decision‐making across diverse management problems as it provides a way to elicit objectives and model trade‐offs, even under uncertainty and data limitations, while including stakeholders impacted by such decisions.
Three‐Dimensional Teleseismic Elastic Reverse‐Time Migration With Deconvolution Imaging Condition and Its Application to Southwest Japan
Authors: Zou Peng , Cheng Jiubing , Wang Tengfei , Zhang Haijiang
Published: April 2024

We have developed a novel deconvolution‐based reverse time migration method to image lithospheric structures using teleseismic data recorded by dense seismic arrays. Unlike traditional approaches that rely on the retrieval of Green's functions (or receiver functions), the new method directly utilizes the recorded three‐component (3‐C) seismic waveforms to reconstruct subsurface wavefields, which has the advantage of avoiding the estimation and removal of source time function. Importantly, it enables the asymptotic estimation of P‐to‐S transmission conversion coefficients at the elastic discontinuities and enhances resolving power for the fine‐scale heterogeneities. Taking these improvements, we have obtained a full three‐dimensional (3‐D) high‐resolution image of the subduction zone beneath southwest Japan. This image provides a comprehensive configuration of the severely deformed subducting plate beneath the Kii Channel and Kinki Peninsula.
Costs of Dust Collection by Trichodesmium: Effect on Buoyancy and Toxic Metal Release
Authors: Wang Siyuan , Zhang Futing , Koedooder Coco , Qafoku Odeta , Basu Subhajit , Krisch Stephan , Visser Anna‐Neva , Eichner Meri , Kessler Nivi , Boiteau Rene M. , Gledhill Martha , Shaked Yeala
Published: April 2024

The marine cyanobacterium Trichodesmium has the remarkable ability to interact with and utilize air‐borne dust as a nutrient source. However, dust may adversely affect Trichodesmium through buoyancy loss and exposure to toxic metals. Our study explored the effect of desert dust on buoyancy and mortality of natural Red Sea puff‐shaped Trichodesmium thiebautii. Sinking velocities and ability of individual colonies to stay afloat with increasing dust loads were studied in sedimentation chambers. Low dust loads of up to ∼400 ng per colony did not impact initial sinking velocity and colonies remained afloat in the chamber. Above this threshold, sinking velocity increased linearly with the colony dust load at a slope matching prediction based on Stoke's law. The potential toxicity of dust was assessed with regards to metal dissolution kinetics, differentiating between rapidly released metals, which may impact surface blooms, and gradually released metals that may impact dust‐centering colonies. Incubations with increasing dust concentrations revealed colony death, but the observed lethal dose far exceeded dust concentrations measured in coastal and open ocean systems. Removal of toxic particles as a mechanism to reduce toxicity was explored using SEM‐EDX imaging of colonies incubated with Cu‐minerals, yet observations did not support this pathway. Combining our current and former experiments, we suggest that in natural settings the nutritional benefits gained by Trichodesmium via dust collection outweigh the risks of buoyancy loss and toxicity. Our data and concepts feed into the growing recognition of the significance of dust for Trichodesmium's ecology and subsequently to ocean productivity.
Brittle‐Ductile Rheological Behavior in Subduction Zones: Effects of Strength Ratio Between Strong and Weak Phases in a Bi‐Phase System
Authors: Maitre A. , Gueydan F. , Thieulot C. , Oliot E.
Published: April 2024

The brittle‐ductile rheological behavior in subduction zones is commonly proposed to explain deep transient slips. Generally observed at large scales in tectonic “mélanges”, here we show that it is also observed at the grain scale in exhumed blueschist metagabbros. In these rocks, petrologic and microstructural observations show a bi‐phase material constituted by strong microfractured magmatic pyroxene clasts located in a weak and ductile lawsonite‐rich metamorphic matrix. To constrain the mechanical conditions allowing the brittle deformation of a clast in a ductile matrix, we used two‐dimensional simple shear numerical experiments. Results show four behaviors: (a) entirely brittle; (b) brittle‐ductile with clast fracturing in a ductile matrix; (c) ductile‐dominant with limited plastic deformation at clast edges; and (d) entirely ductile. We propose that the conditions of the brittle‐ductile behavior, commonly associated with deep transient slips, are controlled by the strength ratio between the strong brittle phase and the weak ductile phase.
Gradient-induced long-range optical pulling force based on photonic band gap
Authors: Lu Wenlong , Krasavin Alexey V. , Lan Sheng , Zayats Anatoly V. , Dai Qiaofeng
Published: April 2024

Optical pulling provides a new degree of freedom in optical manipulation. It is generally believed that long-range optical pulling forces cannot be generated by the gradient of the incident field. Here, we theoretically propose and numerically demonstrate the realization of a long-range optical pulling force stemming from a self-induced gradient field in the manipulated object. In analogy to potential barriers in quantum tunnelling, we use a photonic band gap design in order to obtain the intensity gradients inside a manipulated object placed in a photonic crystal waveguide, thereby achieving a pulling force. Unlike the usual scattering-type optical pulling forces, the proposed gradient-field approach does not require precise elimination of the reflection from the manipulated objects. In particular, the Einstein-Laub formalism is applied to design this unconventional gradient force. The magnitude of the force can be enhanced by a factor of up to 50 at the optical resonance of the manipulated object in the waveguide, making it insensitive to absorption. The developed approach helps to break the limitation of scattering forces to obtain long-range optical pulling for manipulation and sorting of nanoparticles and other nano-objects. The developed principle of using the band gap to obtain a pulling force may also be applied to other types of waves, such as acoustic or water waves, which are important for numerous applications.
Exercise mitigates a gut microbiota-mediated reduction in adult hippocampal neurogenesis and associated behaviours in rats
Authors: Nicolas Sarah , Dohm-Hansen Sebastian , Lavelle Aonghus , Bastiaanssen Thomaz F. S. , English Jane A. , Cryan John F. , Nolan Yvonne M.
Published: April 2024

Lifestyle factors, especially exercise, impact the manifestation and progression of psychiatric and neurodegenerative disorders such as depression and Alzheimer’s disease, mediated by changes in hippocampal neuroplasticity. The beneficial effects of exercise may be due to its promotion of adult hippocampal neurogenesis (AHN). Gut microbiota has also been showed to be altered in a variety of brain disorders, and disturbances of the microbiota have resulted in alterations in brain and behaviour. However, whether exercise can counteract the negative effects of altered gut microbiota on brain function remains under explored. To this end, chronic disruption of the gut microbiota was achieved using an antibiotic cocktail in rats that were sedentary or allowed voluntary access to running wheels. Sedentary rats with disrupted microbiota displayed impaired performance in hippocampal neurogenesis-dependent tasks: the modified spontaneous location recognition task and the novelty suppressed feeding test. Performance in the elevated plus maze was also impaired due to antibiotics treatment. These behaviours, and an antibiotics-induced reduction in AHN were attenuated by voluntary exercise. The effects were independent of changes in the hippocampal metabolome but were paralleled by caecal metabolomic changes. Taken together these data highlight the importance of the gut microbiota in AHN-dependent behaviours and demonstrate the power of lifestyle factors such as voluntary exercise to attenuate these changes.
Cell Painting-based bioactivity prediction boosts high-throughput screening hit-rates and compound diversity
Authors: Fredin Haslum Johan , Lardeau Charles-Hugues , Karlsson Johan , Turkki Riku , Leuchowius Karl-Johan , Smith Kevin , Müllers Erik
Published: April 2024

Identifying active compounds for a target is a time- and resource-intensive task in early drug discovery. Accurate bioactivity prediction using morphological profiles could streamline the process, enabling smaller, more focused compound screens. We investigate the potential of deep learning on unrefined single-concentration activity readouts and Cell Painting data, to predict compound activity across 140 diverse assays. We observe an average ROC-AUC of 0.744 ± 0.108 with 62% of assays achieving ≥0.7, 30% ≥0.8, and 7% ≥0.9. In many cases, the high prediction performance can be achieved using only brightfield images instead of multichannel fluorescence images. A comprehensive analysis shows that Cell Painting-based bioactivity prediction is robust across assay types, technologies, and target classes, with cell-based assays and kinase targets being particularly well-suited for prediction. Experimental validation confirms the enrichment of active compounds. Our findings indicate that models trained on Cell Painting data, combined with a small set of single-concentration data points, can reliably predict the activity of a compound library across diverse targets and assays while maintaining high hit rates and scaffold diversity. This approach has the potential to reduce the size of screening campaigns, saving time and resources, and enabling primary screening with more complex assays.
Kalium channelrhodopsins effectively inhibit neurons
Authors: Ott Stanislav , Xu Sangyu , Lee Nicole , Hong Ivan , Anns Jonathan , Suresh Danesha Devini , Zhang Zhiyi , Zhang Xianyuan , Harion Raihanah , Ye Weiying , Chandramouli Vaishnavi , Jesuthasan Suresh , Saheki Yasunori , Claridge-Chang Adam
Published: April 2024

The analysis of neural circuits has been revolutionized by optogenetic methods. Light-gated chloride-conducting anion channelrhodopsins (ACRs)—recently emerged as powerful neuron inhibitors. For cells or sub-neuronal compartments with high intracellular chloride concentrations, however, a chloride conductance can have instead an activating effect. The recently discovered light-gated, potassium-conducting, kalium channelrhodopsins (KCRs) might serve as an alternative in these situations, with potentially broad application. As yet, KCRs have not been shown to confer potent inhibitory effects in small genetically tractable animals. Here, we evaluated the utility of KCRs to suppress behavior and inhibit neural activity in Drosophila, Caenorhabditiselegans, and zebrafish. In direct comparisons with ACR1, a KCR1 variant with enhanced plasma-membrane trafficking displayed comparable potency, but with improved properties that include reduced toxicity and superior efficacy in putative high-chloride cells. This comparative analysis of behavioral inhibition between chloride- and potassium-selective silencing tools establishes KCRs as next-generation optogenetic inhibitors for in vivo circuit analysis in behaving animals.
Quantum critical phase of FeO spans conditions of Earth’s lower mantle
Authors: Ho Wai-Ga D. , Zhang Peng , Haule Kristjan , Jackson Jennifer M. , Dobrosavljević Vladimir , Dobrosavljevic Vasilije V.
Published: April 2024

Seismic and mineralogical studies have suggested regions at Earth’s core-mantle boundary may be highly enriched in FeO, reported to exhibit metallic behavior at extreme pressure-temperature (P–T) conditions. However, underlying electronic processes in FeO remain poorly understood. Here we explore the electronic structure of B1-FeO at extreme conditions with large-scale theoretical modeling using state-of-the-art embedded dynamical mean field theory (eDMFT). Fine sampling of the phase diagram reveals that, instead of sharp metallization, compression of FeO at high temperatures induces a gradual orbitally selective insulator-metal transition. Specifically, at P–T conditions of the lower mantle, FeO exists in an intermediate quantum critical state, characteristic of strongly correlated electronic matter. Transport in this regime, distinct from insulating or metallic behavior, is marked by incoherent diffusion of electrons in the conducting t2g orbital and a band gap in the eg orbital, resulting in moderate electrical conductivity (~105 S/m) with modest P–T dependence as observed in experiments. Enrichment of solid FeO can thus provide a unifying explanation for independent observations of low seismic velocities and elevated electrical conductivities in heterogeneities at Earth’s mantle base.
Flexible TAM requirement of TnpB enables efficient single-nucleotide editing with expanded targeting scope
Authors: Feng Xu , Xu Ruyi , Liao Jianglan , Zhao Jingyu , Zhang Baochang , Xu Xiaoxiao , Zhao Pengpeng , Wang Xiaoning , Yao Jianyun , Wang Pengxia , Wang Xiaoxue , Han Wenyuan , She Qunxin
Published: April 2024

TnpBs encoded by the IS200/IS605 family transposon are among the most abundant prokaryotic proteins from which type V CRISPR-Cas nucleases may have evolved. Since bacterial TnpBs can be programmed for RNA-guided dsDNA cleavage in the presence of a transposon-adjacent motif (TAM), these nucleases hold immense promise for genome editing. However, the activity and targeting specificity of TnpB in homology-directed gene editing remain unknown. Here we report that a thermophilic archaeal TnpB enables efficient gene editing in the natural host. Interestingly, the TnpB has different TAM requirements for eliciting cell death and for facilitating gene editing. By systematically characterizing TAM variants, we reveal that the TnpB recognizes a broad range of TAM sequences for gene editing including those that do not elicit apparent cell death. Importantly, TnpB shows a very high targeting specificity on targets flanked by a weak TAM. Taking advantage of this feature, we successfully leverage TnpB for efficient single-nucleotide editing with templated repair. The use of different weak TAM sequences not only facilitates more flexible gene editing with increased cell survival, but also greatly expands targeting scopes, and this strategy is probably applicable to diverse CRISPR-Cas systems.
Chromosome organization shapes replisome dynamics in Caulobacter crescentus
Authors: Zhang Chen , Joseph Asha Mary , Casini Laurent , Collier Justine , Badrinarayanan Anjana , Manley Suliana
Published: April 2024

DNA replication in bacteria takes place on highly compacted chromosomes, where segregation, transcription, and repair must occur simultaneously. Within this dynamic environment, colocalization of sister replisomes has been observed in many bacterial species, driving the hypothesis that a physical linker may tether them together. However, replisome splitting has also been reported in many of the same species, leaving the principles behind replisome organization a long-standing puzzle. Here, by tracking the replisome β-clamp subunit in live Caulobacter crescentus, we find that rapid DNA segregation can give rise to a second focus which resembles a replisome, but does not replicate DNA. Sister replisomes can remain colocalized, or split apart to travel along DNA separately upon disruption of chromosome inter-arm alignment. Furthermore, chromosome arm-specific replication-transcription conflicts differentially modify replication speed on the two arms, facilitate the decoupling of the two replisomes. With these observations, we conclude that the dynamic chromosome organization flexibly shapes the organization of sister replisomes, and we outline principles which can help to reconcile previously conflicting models of replisome architecture.
Rapid autopsies to enhance metastatic research: the UPTIDER post-mortem tissue donation program
Authors: Geukens Tatjana , De Schepper Maxim , Van Den Bogaert Wouter , Van Baelen Karen , Maetens Marion , Pabba Anirudh , Mahdami Amena , Leduc Sophia , Isnaldi Edoardo , Nguyen Ha-Linh , Bachir Imane , Hajipirloo Maysam , Zels Gitte , Van Cauwenberge Josephine , Borremans Kristien , Vandecaveye Vincent , Weynand Birgit , Vermeulen Peter , Leucci Eleonora , Baietti Maria Francesca , Sflomos George , Battista Laura , Brisken Cathrin , Derksen Patrick W. B. , Koorman Thijs , Visser Daan , Scheele Colinda L. G. J. , Thommen Daniela S. , Hatse Sigrid , Fendt Sarah-Maria , Vanderheyden Evy , Van Brussel Thomas , Schepers Rogier , Boeckx Bram , Lambrechts Diether , Marano Giuseppe , Biganzoli Elia , Smeets Ann , Nevelsteen Ines , Punie Kevin , Neven Patrick , Wildiers Hans , Richard François , Floris Giuseppe , Desmedt Christine
Published: April 2024

Research on metastatic cancer has been hampered by limited sample availability. Here we present the breast cancer post-mortem tissue donation program UPTIDER and show how it enabled sampling of a median of 31 (range: 5-90) metastases and 5-8 liquids per patient from its first 20 patients. In a dedicated experiment, we show the mild impact of increasing time after death on RNA quality, transcriptional profiles and immunohistochemical staining in tumor tissue samples. We show that this impact can be counteracted by organ cooling. We successfully generated ex vivo models from tissue and liquid biopsies from distinct histological subtypes of breast cancer. We anticipate these and future findings of UPTIDER to elucidate mechanisms of disease progression and treatment resistance and to provide tools for the exploration of precision medicine strategies in the metastatic setting.
Optimizing self-organized study orders: combining refutations and metacognitive prompts improves the use of interleaved practice
Authors: Onan Erdem , Biwer Felicitas , Abel Roman , Wiradhany Wisnu , de Bruin Anique
Published: April 2024

During category learning, students struggle to create an optimal study order: They often study one category at a time (i.e., blocked practice) instead of alternating between different categories (i.e., interleaved practice). Several interventions to improve self-study of categorical learning have been proposed, but these interventions have only been tested in learning tasks where students did not create the study order themselves. Instead, they decided which type of study order to follow. This pre-registered experiment examined whether an intervention that combines refutations and metacognitive prompts can enhance students’ engagement in interleaved practice, specifically when they organize the learning materials themselves. Ninety-one undergraduate students were randomized into the intervention and control condition and learned visual categories. Prior to the intervention, students used more blocked practice. After the intervention, the use of interleaved practice significantly increased in both immediate and delayed-transfer tasks. More interleaved practice was associated with better classification performance. Our findings indicate that refutations and metacognitive prompts form a strong intervention that corrects students’ erroneous beliefs and increases their engagement in interleaved practice.
Age and sex influence antibody profiles associated with tuberculosis progression
Authors: Davies Leela R. L. , Wang Chuangqi , Steigler Pia , Bowman Kathryn A. , Fischinger Stephanie , Hatherill Mark , Fisher Michelle , Mbandi Stanley Kimbung , Rodo Miguel , Ottenhoff Tom H. M. , Dockrell Hazel M. , Sutherland Jayne S. , Mayanja-Kizza Harriet , Boom W. Henry , Walzl Gerhard , Kaufmann Stefan H. E. , Nemes Elisa , Scriba Thomas J. , Lauffenburger Douglas , Alter Galit , Fortune Sarah M.
Published: April 2024

Antibody features vary with tuberculosis (TB) disease state. Whether clinical variables, such as age or sex, influence associations between Mycobacterium tuberculosis-specific antibody responses and disease state is not well explored. Here we profiled Mycobacterium tuberculosis-specific antibody responses in 140 TB-exposed South African individuals from the Adolescent Cohort Study. We identified distinct response features in individuals progressing to active TB from non-progressing, matched controls. A multivariate antibody score differentially associated with progression (SeroScore) identified progressors up to 2 years before TB diagnosis, earlier than that achieved with the RISK6 transcriptional signature of progression. We validated these antibody response features in the Grand Challenges 6–74 cohort. Both the SeroScore and RISK6 correlated better with risk of TB progression in adolescents compared with adults, and in males compared with females. This suggests that age and sex are important, underappreciated modifiers of antibody responses associated with TB progression.
New method for calculating the windward area of irregular fragments
Authors: Liu Xing-yu , Ouyang Di-hua , Wang Jia-ying , Guo Zhi-yong , Yang Chun-hai
Published: April 2024

Average windward area is an important index for calculating the trajectory, velocity attenuation and terminal effect of explosive fragments. In order to solve the problems that existing theoretical method cannot calculate windward area of irregular fragment and experiment method is not convenient for automatic calculation and has low accuracy, a Monte Carlo subdivision projection simulation algorithm is proposed. The average windward area of arbitrary shaped fragments can be obtained with coordinate translation, random rotation, plane projection, convex-hull triangulation, concave boundary searching and sorting with maximum edge length constraint, subdivision area calculation, and averaging by thousands of cycles. Results show that projection area obtained by the subdivision projection algorithm is basically the same as that obtained by software method of computer aided design. Moreover, the maximum calculation error of the algorithm is less than 7%, and its accuracy is much higher than that of the equivalent ellipsoid method. The average windward area calculated by the Monte Carlo subdivision projection simulation algorithm is consistent with theoretical formula for prefabricated fragments, and the error is less than 3%. The convergence and accuracy of the Monte Carlo subdivision projection algorithm are better than those of the icosahedral uniform orientation method.
Mapping philanthropic support of science
Authors: Shekhtman Louis M. , Gates Alexander J. , Barabási Albert-László
Published: April 2024

While philanthropic support for science has increased in the past decade, there is limited quantitative knowledge about the patterns that characterize it and the mechanisms that drive its distribution. Here, we map philanthropic funding to universities and research institutions based on IRS tax forms from 685,397 non-profit organizations. We identify nearly one million grants supporting institutions involved in science and higher education, finding that in volume and scope, philanthropy is a significant source of funds, reaching an amount that rivals some of the key federal agencies like the NSF and NIH. Our analysis also reveals that philanthropic funders tend to focus locally, indicating that criteria beyond research excellence play an important role in funding decisions, and that funding relationships are stable, i.e. once a grant-giving relationship begins, it tends to continue in time. Finally, we show that the bipartite funder-recipient network displays a highly overrepresented motif indicating that funders who share one recipient also share other recipients and we show that this motif contains predictive power for future funding relationships. We discuss the policy implications of our findings on inequality in science, scientific progress, and the role of quantitative approaches to philanthropy.
A multi-omics analysis-based model to predict the prognosis of low-grade gliomas
Authors: Du Zhijie , Jiang Yuehui , Yang Yueling , Kang Xiaoyu , Yan Jing , Liu Baorui , Yang Mi
Published: April 2024

Lower-grade gliomas (LGGs) exhibit highly variable clinical behaviors, while classic histology characteristics cannot accurately reflect the authentic biological behaviors, clinical outcomes, and prognosis of LGGs. In this study, we carried out analyses of whole exome sequencing, RNA sequencing and DNA methylation in primary vs. recurrent LGG samples, and also combined the multi-omics data to construct a prognostic prediction model. TCGA-LGG dataset was searched for LGG samples. 523 samples were used for whole exome sequencing analysis, 532 for transcriptional analysis, and 529 for DNA methylation analysis. LASSO regression was used to screen genes with significant association with LGG survival from the frequently mutated genes, differentially expressed genes, and differentially methylated genes, whereby a prediction model for prognosis of LGG was further constructed and validated. The most frequently mutated diver genes in LGGs were IDH1 (77%), TP53 (48%), ATRX (37%), etc. Top significantly up-regulated genes were C6orf15, DAO, MEOX2, etc., and top significantly down-regulated genes were DMBX1, GPR50, HMX2, etc. 2077 genes were more and 299 were less methylated in recurrent vs. primary LGG samples. Thirty-nine genes from the above analysis were included to establish a prediction model of survival, which showed that the high-score group had a very significantly shorter survival than the low-score group in both training and testing sets. ROC analysis showed that AUC was 0.817 for the training set and 0.819 for the testing set. This study will be beneficial to accurately predict the survival of LGGs to identify patients with poor prognosis to take specific treatment as early, which will help improve the treatment outcomes and prognosis of LGG.
SpEx: a German-language dataset of speech and executive function performance
Authors: Camilleri Julia A. , Volkening Julia , Heim Stefan , Mochalski Lisa N. , Neufeld Hannah , Schlothauer Natalie , Kuhles Gianna , Eickhoff Simon B. , Weis Susanne
Published: April 2024

This work presents data from 148 German native speakers (20–55 years of age), who completed several speaking tasks, ranging from formal tests such as word production tests to more ecologically valid spontaneous tasks that were designed to mimic natural speech. This speech data is supplemented by performance measures on several standardised, computer-based executive functioning (EF) tests covering domains of working-memory, cognitive flexibility, inhibition, and attention. The speech and EF data are further complemented by a rich collection of demographic data that documents education level, family status, and physical and psychological well-being. Additionally, the dataset includes information of the participants’ hormone levels (cortisol, progesterone, oestradiol, and testosterone) at the time of testing. This dataset is thus a carefully curated, expansive collection of data that spans over different EF domains and includes both formal speaking tests as well as spontaneous speaking tasks, supplemented by valuable phenotypical information. This will thus provide the unique opportunity to perform a variety of analyses in the context of speech, EF, and inter-individual differences, and to our knowledge is the first of its kind in the German language. We refer to this dataset as SpEx since it combines speech and executive functioning data. Researchers interested in conducting exploratory or hypothesis-driven analyses in the field of individual differences in language and executive functioning, are encouraged to request access to this resource. Applicants will then be provided with an encrypted version of the data which can be downloaded.
Bacillus velezensis iturins inhibit the hemolytic activity of Staphylococcus aureus
Authors: Sabino Yasmin Neves Vieira , de Araújo Domingues Katialaine Corrêa , O’Connor Paula Mary , Marques Pedro Henrique , Santos Eduardo Horta , Tótola Marcos Rogério , Abreu Lucas Magalhães , de Queiroz Marisa Vieira , Cotter Paul D. , Mantovani Hilario Cuquetto
Published: April 2024

Bovine mastitis caused by S. aureus has a major economic impact on the dairy sector. With the crucial need for new therapies, anti-virulence strategies have gained attention as alternatives to antibiotics. Here we aimed to identify novel compounds that inhibit the production/activity of hemolysins, a virulence factor of S. aureus associated with mastitis severity. We screened Bacillus strains obtained from diverse sources for compounds showing anti-hemolytic activity. Our results demonstrate that lipopeptides produced by Bacillus spp. completely prevented the hemolytic activity of S. aureus at certain concentrations. Following purification, both iturins, fengycins, and surfactins were able to reduce hemolysis caused by S. aureus, with iturins showing the highest anti-hemolytic activity (up to 76% reduction). The lipopeptides showed an effect at the post-translational level. Molecular docking simulations demonstrated that these compounds can bind to hemolysin, possibly interfering with enzyme action. Lastly, molecular dynamics analysis indicated general stability of important residues for hemolysin activity as well as the presence of hydrogen bonds between iturins and these residues, with longevous interactions. Our data reveals, for the first time, an anti-hemolytic activity of lipopeptides and highlights the potential application of iturins as an anti-virulence therapy to control bovine mastitis caused by S. aureus.
Effects of expectation on face perception and its association with expertise
Authors: Mares Inês , Smith Fraser W. , Goddard E. J. , Keighery Lianne , Pappasava Michael , Ewing Louise , Smith Marie L.
Published: April 2024

Perceptual decisions are derived from the combination of priors and sensorial input. While priors are broadly understood to reflect experience/expertise developed over one’s lifetime, the role of perceptual expertise at the individual level has seldom been directly explored. Here, we manipulate probabilistic information associated with a high and low expertise category (faces and cars respectively), while assessing individual level of expertise with each category. 67 participants learned the probabilistic association between a color cue and each target category (face/car) in a behavioural categorization task. Neural activity (EEG) was then recorded in a similar paradigm in the same participants featuring the previously learned contingencies without the explicit task. Behaviourally, perception of the higher expertise category (faces) was modulated by expectation. Specifically, we observed facilitatory and interference effects when targets were correctly or incorrectly expected, which were also associated with independently measured individual levels of face expertise. Multivariate pattern analysis of the EEG signal revealed clear effects of expectation from 100 ms post stimulus, with significant decoding of the neural response to expected vs. not stimuli, when viewing identical images. Latency of peak decoding when participants saw faces was directly associated with individual level facilitation effects in the behavioural task. The current results not only provide time sensitive evidence of expectation effects on early perception but highlight the role of higher-level expertise on forming priors.
Ferroelectric capacitors and field-effect transistors as in-memory computing elements for machine learning workloads
Authors: Yu Eunseon , K Gaurav Kumar , Saxena Utkarsh , Roy Kaushik
Published: April 2024

This study discusses the feasibility of Ferroelectric Capacitors (FeCaps) and Ferroelectric Field-Effect Transistors (FeFETs) as In-Memory Computing (IMC) elements to accelerate machine learning (ML) workloads. We conducted an exploration of device fabrication and proposed system-algorithm co-design to boost performance. A novel FeCap device, incorporating an interfacial layer (IL) and $$\text {Hf}_{0.5}\text {Zr}_{0.5}\text {O}_2$$

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(HZO), ensures a reduction in operating voltage and enhances HZO scaling while being compatible with CMOS circuits. The IL also enriches ferroelectricity and retention properties. When integrated into crossbar arrays, FeCaps and FeFETs demonstrate their effectiveness as IMC components, eliminating sneak paths and enabling selector-less operation, leading to notable improvements in energy efficiency and area utilization. However, it is worth noting that limited capacitance ratios in FeCaps introduced errors in multiply-and-accumulate (MAC) computations. The proposed co-design approach helps in mitigating these errors and achieves high accuracy in classifying the CIFAR-10 dataset, elevating it from a baseline of 10% to 81.7%. FeFETs in crossbars, with a higher on-off ratio, outperform FeCaps, and our proposed charge-based sensing scheme achieved at least an order of magnitude reduction in power consumption, compared to prevalent current-based methods.