bluuebunny/crossref_metadata_2025 huggingface dataset:
Financial Worries, Health Complaints, and Career Exploration: The Role of Action Crises
Authors: Schmitt Antje , Heihal Teodora I. , Zacher Hannes
Published: April 2024

Financial worries, a distressing emotional state prompted by perceived threats to financial resources, are particularly prevalent among employees during economic downturns. This study investigates associations between financial worries and employees’ health and career behaviors, drawing on conservation of resources theory and the self-regulation literature. We propose that financial worries are not only positively related to health complaints, but also positively related to employees’ career exploration as a coping mechanism. In addition, we explore how financial worries are associated with action crises—internal conflicts about whether to leave one’s job—and how these crises may help explain the relationships between worries and employee outcomes. In a two-month time-lagged study with 312 employees, we observed a positive association between financial worries and health complaints, but no significant association with career exploration. Furthermore, the experience of an action crisis mediated the relation between financial worries and health complaints. Action crises were positively related to subsequent career exploration, and we established a significant indirect effect of financial worries on career exploration through action crises. This research contributes to a better understanding of the potential health-related and behavioral outcomes of financial worries by introducing action crisis as a cognitive–emotional mechanism. It also expands the limited research on antecedents and consequences of action crises and responds to calls for research on the predictors of career exploration as a career self-management behavior. We discuss the study’s implications for theory, research, and practice in light of the its limitations.
Random walk simulation by population dynamics P systems
Authors: Orellana-Martín David , Andreu-Guzmán José A. , Graciani Carmen , Riscos-Núñez Agustín , Pérez-Jiménez Mario J.
Published: April 2024

PDP systems have been widely used for real-life applications, such as systems biology, ecosystems, physics or economy, among others. Complex systems related with these areas are simulated in the framework of Membrane Computing using objects and membranes that can represent entities or places in the real-life process. In physics, the study of a particle in different fluids, depending on their composition, is really interesting for several applications. A first approximation to this field is to think that particles move randomly in the available space, without any force that constrains their movements. This behavior is known as random walk, and it is used not only in physics but in economics, genetics, and ecology among other areas. In this paper, we introduce generic PDP systems for simulating the behavior of particles, both for one-dimensional spaces and for two-dimensional spaces, using different simulators to analyze the computational resources consumed.
Local value creation for developing business relationships: An SME case study in the pasta industry
Authors: Runfola Andrea , Monteverde Giulia , Picciotti Antonio
Published: April 2024

Drawing on the market-as-network approach from the Industrial Marketing and Purchasing (IMP) Group, this paper explores how small and medium-sized companies can leverage their network to become network orchestrators, co-creating value locally and developing business relationships. Specifically, the paper addresses the following research questions: RQ1) How can SMEs act as network orchestrators for local value co-creation? RQ2) How can SMEs leverage local value to develop business relationships? Methodologically, the industrial network theory is applied to an exploratory and single case study of an Italian food company in the pasta sector, Fabianelli. This enterprise boasts a historical tradition firmly linked to its origins and a solid attachment to the Tuscany region where it is located. The paper identifies specific actors, resources, and activities defining a company’s network orchestrator role. Further, it analyzes the value co-created locally to discuss four strategies used by Fabianelli to develop relationships with national and international actors.
Surface topography prediction of slider races using formed grinding wheel shape and material removal mechanism
Authors: Kang Mingxia , Hua Dezheng , Li Yongbo , Królczyk Grzegorz M. , Liu Xinhua , Gupta Munish Kumar , Królczyk J. B. , Li Z.
Published: April 2024

Compared with the roughness, the three-dimensional (3D) topography parameters, surface microstructure geometric characteristics and other information can more fully evaluate the grinding quality of the slider raceway surface. In this paper, based on the 3D topography model of the abrasive particle distribution on the surface of the formed grinding wheel, the material removal mechanism between the abrasive particle and the raceway surface is analyzed. With the undeformed chip thickness distribution model as the intermediate variable, the 3D topography model of the slider raceway surface is established, and the model verification is carried out from the roughness and the geometric characteristics of the surface microstructure, respectively. At the same time, the surface microstructure is extracted from the topography model, and the effects of different grinding process parameters on the geometric characteristics such as the height to width ratio, depth to width ratio and distribution density of groove, convex peak and peak valley structures are studied. Results are shown that AS,TH increase from [0.05 0.6 μm] to [0.25 0.8 μm] and FGH grows from [0.11 1.05 μm] to [0.5 1.61 μm] when the grinding depth rises from 1 μm to 4 μm. AS, TH are firstly decreased from [0.17 0.61 μm] to [0.08 0.52 μm] and then increased to [0.26 0.78 μm], and the FGH declines from [0.34 1.01 μm] to [0.16 0.86 μm] and then increases to [0.51 1.38 μm] with the feeding speed is in [25, 28 m/min]. In addition, in the range of grinding wheel linear velocity [28, 34 m/s], the AS,TH decreases from [0.19 0.81 μm] to [0.1 0.55 μm] and the FGH decreases from [0.55 1.6 μm] to [0.2 1.1 μm]. This can prepare for the subsequent research on the impact of the topography characteristics on the friction coefficient and wear amount of the slider raceway surface.
Well-Posedness of the Two-Component Fornberg–Whitham System in Besov Spaces
Authors: Dutta Prerona
Published: April 2024

The present paper establishes well-posedness for the two-component Fornberg–Whitham system in Besov spaces. First the existence and uniqueness of its solution is proved, then it is shown that the corresponding data-to-solution map is continuous, provided the initial data belong to Besov spaces.
“Hot Forests”: Spatial Concentration of Forest “Pyro-Terrorism” in Israel
Authors: Perry Simon , Amram Shai
Published: April 2024

One of the areas in terrorism research that has not been adequately examined is the geographic concentration of pyro-terrorism (PT) attacks. The literature related to the geographical distribution of terror generally focuses on macro-places (continents, countries and regions) and micro-places – “hot spots”. However, to our knowledge, the geographical distribution of terror in forests has yet to be studied. The findings of “hot spots” studies have great relevance for law enforcement practitioners. This study examines the spatial characteristics of forest PT and whether there is a concentration of PT attacks in a limited number of “hot forests” that are stable over time. This study examined the entire population of suspected forest PT in Israel between 2008 and 2022 (excluding 2016), totalling 2,297 attacks. The research revealed high spatial clustering of forest PT attacks concentrated in specific “hot forests” and that they were stable over time. In conclusion, the concentration of PT attacks calls for a specialized counterterrorism response, equivalent to “hot spots policing”, based on the characteristics of potential terrorist hot forests.
FIRST EIGENVALUE CHARACTERISATION OF CLIFFORD HYPERSURFACES AND VERONESE SURFACES
Authors: WU PEIYI
Published: April 2024

We give a sharp estimate for the first eigenvalue of the Schrödinger operator
$L:=-\Delta -\sigma $
which is defined on the closed minimal submanifold
$M^{n}$
in the unit sphere
$\mathbb {S}^{n+m}$
, where
$\sigma $
is the square norm of the second fundamental form.
The Rushdie Affair and the Politics of Multicultural Britain
Authors: Connell Kieran
Published: April 2024

It is more than thirty years since Ayatollah Khomeini, the supreme leader of Iran, issued a fatwa (religious decree) calling for the execution of the British-Indian novelist Salman Rushdie, whose third novel, The Satanic Verses, was published in 1988. But the ‘Rushdie Affair’ has yet to be subject to a sustained analysis by historians. Journalists and political scientists continue to focus on the fatwa, despite the fact the protests against the novel in Britain – where The Satanic Verses is primarily set – predated Khomeini’s decree by two months. This article fills this lacuna by shifting attention onto the emergence of the campaign against The Satanic Verses in Britain and in Bradford especially, where a copy of Rushdie’s ‘blasphemous’ novel was infamously burnt by Muslim protestors. It shows how an earlier set of campaigns fought in Bradford by Muslim activists paved the way for the city to become a key site of protest against both Rushdie and his novel. The protests that greeted The Satanic Verses were shaped by the contradictory nature of Britain’s emergence as a multicultural society, I argue, and the political complexities thrown up by the hybridized milieu Rushdie had sought to use his fiction to evoke.
Proton acceleration from optically tailored high-density gas jet targets
Authors: Maitrallain A. , Marquès J.-R. , Bontemps K. , Bonvalet J. , Atukpor E.F. , Bagnoud V. , Carrière T. , Hannachi F. , Henares J.L. , Hornung J. , Huber A. , d'Humières E. , Lancia L. , Loiseau P. , Nicolaï P. , Santos J. , Tikhonchuk V. , Zielbauer B. , Tarisien M.
Published: April 2024

Laser-driven ion acceleration is well established using solid targets mainly in the target normal sheath acceleration regime. To follow the increasing repetition rate available on high-intensity lasers, the use of high-density gas targets has been explored in the past decade. When interacting with targets reaching densities close to the critical one, the laser pulse can trigger different acceleration mechanisms such as Collisionless Shock Acceleration (CSA) or hole boring. Particle-in-cell simulations using ideal target profiles show that CSA can accelerate a collimated, narrow energy spread and few hundreds of megaelectronvolts ion beam on the laser axis. Nevertheless, in real experiments, the laser will not only interact with an overcritical, thin plasma slab with sharp density gradients, but also with lower density regions surrounding the core of the gas jet, extending to several hundreds of micrometres. The interaction of the laser with these lower density wings will lead to nonlinear effects that will reduce the available energy to drive the shock in the high-density region of the target. Optically tailoring this target could mitigate that issue. Recent experiments conducted on different laser facilities aimed at testing several tailoring configurations. We first tested a scheme with a copropagating picosecond prepulse to create a lower density plasma channel to facilitate the propagation of the main pulse, while the second one was a transverse tailoring driven by nanosecond laser pulses to generate blast waves and form a high-density plasma slab. The main results will be presented here and the methods compared.
Late-life divorce and familyhood interplaying: a familial and dyadic perspective
Authors: Koren Chaya , Cohen Yafit , Egert Michal , Demeter Naor
Published: April 2024

Late-life divorce is a growing phenomenon in the Western world, likely to expand due to increasing expectancy and changes in marital and family values. However, existing research on divorce and its consequences for offspring focuses on young and middle-aged adults, analysing individual rather than familial/dyadic perspectives. Accordingly, our study employs a holistic perspective on the family unit following late-life divorce which is especially relevant to societies that value familism as an essential element in individuals' lives. Coincidingly, the term familyhood expresses an atmosphere of closeness and unity among family members and is a commonly used expression in Israel. Using family systems as a framework, our aim was to examine how, if at all, familyhood is experienced after divorce considering how it was experienced prior to divorce from a long-term marriage in Israel. Semi-structured, in-depth qualitative interviews (N = 72) were conducted separately with divorcees aged 60–81 who divorced at age 56–68 (N = 44), and with their adult children aged 19–40 at the time of their parents' divorce (N = 28). Interviews were given thematic analysis and dyadic qualitative analysis. The findings reveal the meaningfulness of familyhood following late-life divorce via a fourfold typology of familyhood continuity/change experienced as present or lacking, before or after divorce. The typology addresses key elements of when, where, by whom and how familyhood is reconstructed, along with strategies to maintain familyhood. Paradoxes inherent in the intersection of divorce and familyhood, discussed within the Israeli sociocultural context, are located between self-determination and familism. Implications are presented.
Cardiac resternotomy after cardiac surgery in kids: CRACK the chest
Authors: Shah Jui , Sefton Ashley , Dentel John , Tilford Bradley , Cashen Katherine
Published: April 2024

Objective:

Emergent resuscitation of postoperative paediatric cardiac surgical patients requires specialised skills and multidisciplinary teamwork. Bedside resternotomy is a rare but life-saving procedure and few studies focus on ways to prepare providers and improve performance. We created a multidisciplinary educational intervention that addressed teamwork and technical skills. We aimed to evaluate the efficiency of the intervention to decrease time to perform critical tasks and improve caregiver comfort.

Methods:

A simulation-based, in situ resternotomy educational intervention was implemented. Pre-intervention data were collected. Educational aids were used weekly during day and night nursing huddles over a three-month period. All ICU charge nurses had separate educational sessions with study personnel and were required to demonstrate competency in all the critical tasks. Post-intervention simulations were performed after intervention and at 6 months and post-intervention surveys were performed.

Results:

A total of 186 providers participated in the intervention. There was a decrease in time to obtain defibrillator, setup resternotomy equipment and internal defibrillator paddles and deliver sedation and fluid (all p < 0.05). Time to escort family from the room and obtain blood was significantly decreased after intervention (p < 0.05). There was no difference in time to first dose of epinephrine, defibrillator pads on the patient, or time to call the cardiovascular surgeon or blood bank. Providers reported increased comfort in identifying equipment needed for resternotomy (p < 0.01) and setting up the internal defibrillator paddles (p < 0.01).

Conclusions:

Implementation of a novel educational intervention increased provider comfort and decreased time to perform critical tasks in an emergent resternotomy scenario.
The emergence of Gaza as a provincial intellectual centre during the Mamluk period
Authors: Amir Or
Published: April 2024

During the Mamluk period (1260–1516), Gaza developed from a minor town into an important city in southern Bilād al-Shām, the capital of an administrative province. This prosperity was the product of substantial and continuous Mamluk investment in the town, the security and stability maintained by this regime, and Gaza's strategic location as the bridge connecting Egypt and Bilād al-Shām. This article will trace the concomitant development of Gaza as a provincial intellectual centre within this context. Combining narrative sources with epigraphic and material evidence, it will show how the growth of Gaza as an administrative centre instigated a flourishing—albeit modest—scholarly scene in the town, which, while strongly connected to and integrated with wider social and intellectual networks within the Sultanate, retained its unique character.
Bilinguals on the footbridge: the role of foreign-language proficiency in moral decision making
Authors: Teitelbaum Dorfman Federico , Kogan Boris , Barttfeld Pablo , García Adolfo M.
Published: April 2024

Socio-cognitive research on bilinguals points to a moral foreign-language effect (MFLE), with more utilitarian choices (e.g., sacrificing someone to save more people) for moral dilemmas presented in the second language (L2) relative to the first language. Yet, inconsistent results highlight the influence of subject-level variables, including a critical underexplored factor: L2 proficiency (L2p). Here we provide a systematic review of 57 bilingualism studies on moral dilemmas, showing that L2p rarely modulates responses to impersonal dilemmas, but it does impact personal dilemmas (with MFLEs proving consistent at intermediate L2p levels but unsystematic at high L2p levels). We propose an empirico-theoretical framework to conceptualize such patterns, highlighting the impact of L2p on four affective mediating factors: mental imagery, inhibitory control, prosocial behavior and numerical processing. Finally, we outline core challenges for the field. These insights open new avenues at the crossing of bilingualism and social cognition research.
Mechanism of phase condensation for chromosome architecture and function
Authors: Park Jeongveen , Kim Jeong-Jun , Ryu Je-Kyung
Published: April 2024

Chromosomal phase separation is involved in a broad spectrum of chromosome organization and functional processes. Nonetheless, the intricacy of this process has left its molecular mechanism unclear. Here, we introduce the principles governing phase separation and its connections to physiological roles in this context. Our primary focus is contrasting two phase separation mechanisms: self-association-induced phase separation (SIPS) and bridging-induced phase separation (BIPS). We provide a comprehensive discussion of the distinct features characterizing these mechanisms and offer illustrative examples that suggest their broad applicability. With a detailed understanding of these mechanisms, we explore their associations with nucleosomes and chromosomal biological functions. This comprehensive review contributes to the exploration of uncharted territory in the intricate interplay between chromosome architecture and function.
3C methods in cancer research: recent advances and future prospects
Authors: Yoon Insoo , Kim Uijin , Jung Kyung Oh , Song Yousuk , Park Taesoo , Lee Dong-Sung
Published: April 2024

In recent years, Hi-C technology has revolutionized cancer research by elucidating the mystery of three-dimensional chromatin organization and its role in gene regulation. This paper explored the impact of Hi-C advancements on cancer research by delving into high-resolution techniques, such as chromatin loops, structural variants, haplotype phasing, and extrachromosomal DNA (ecDNA). Distant regulatory elements interact with their target genes through chromatin loops. Structural variants contribute to the development and progression of cancer. Haplotype phasing is crucial for understanding allele-specific genomic rearrangements and somatic clonal evolution in cancer. The role of ecDNA in driving oncogene amplification and drug resistance in cancer cells has also been revealed. These innovations offer a deeper understanding of cancer biology and the potential for personalized therapies. Despite these advancements, challenges, such as the accurate mapping of repetitive sequences and precise identification of structural variants, persist. Integrating Hi-C with multiomics data is key to overcoming these challenges and comprehensively understanding complex cancer genomes. Thus, Hi-C is a powerful tool for guiding precision medicine in cancer research and treatment.
Resolution of tonic concentrations of highly similar neurotransmitters using voltammetry and deep learning
Authors: Goyal Abhinav , Yuen Jason , Sinicrope Stephen , Winter Bailey , Randall Lindsey , Rusheen Aaron E. , Blaha Charles D. , Bennet Kevin E. , Lee Kendall H. , Shin Hojin , Oh Yoonbae
Published: April 2024

With advances in our understanding regarding the neurochemical underpinnings of neurological and psychiatric diseases, there is an increased demand for advanced computational methods for neurochemical analysis. Despite having a variety of techniques for measuring tonic extracellular concentrations of neurotransmitters, including voltammetry, enzyme-based sensors, amperometry, and in vivo microdialysis, there is currently no means to resolve concentrations of structurally similar neurotransmitters from mixtures in the in vivo environment with high spatiotemporal resolution and limited tissue damage. Since a variety of research and clinical investigations involve brain regions containing electrochemically similar monoamines, such as dopamine and norepinephrine, developing a model to resolve the respective contributions of these neurotransmitters is of vital importance. Here we have developed a deep learning network, DiscrimNet, a convolutional autoencoder capable of accurately predicting individual tonic concentrations of dopamine, norepinephrine, and serotonin from both in vitro mixtures and the in vivo environment in anesthetized rats, measured using voltammetry. The architecture of DiscrimNet is described, and its ability to accurately predict in vitro and unseen in vivo concentrations is shown to vastly outperform a variety of shallow learning algorithms previously used for neurotransmitter discrimination. DiscrimNet is shown to generalize well to data captured from electrodes unseen during model training, eliminating the need to retrain the model for each new electrode. DiscrimNet is also shown to accurately predict the expected changes in dopamine and serotonin after cocaine and oxycodone administration in anesthetized rats in vivo. DiscrimNet therefore offers an exciting new method for real-time resolution of in vivo voltammetric signals into component neurotransmitters.
Non-canonical deubiquitination of OTUB1 induces IFNγ-mediated cell cycle arrest via regulation of p27 stability
Authors: Lee Seul Gi , Woo Seon Min , Seo Seung Un , Lee Hyun Shik , Kim Sang Hyun , Chang Young-Chae , Cho Hyo Je , Yook Simmyung , Nam Ju-Ock , Kwon Taeg Kyu
Published: April 2024

The deubiquitinase OTUB1, implicated as a potential oncogene in various tumors, lacks clarity in its regulatory mechanism in tumor progression. Our study investigated the effects and underlying mechanisms of OTUB1 on the breast cancer cell cycle and proliferation in IFNγ stimulation. Loss of OTUB1 abrogated IFNγ-induced cell cycle arrest by regulating p27 protein expression, whereas OTUB1 overexpression significantly enhanced p27 expression even without IFNγ treatment. Tyr26 phosphorylation residue of OTUB1 directly bound to p27, modulating its post-translational expression. Furthermore, we identified crucial lysine residues (K134, K153, and K163) for p27 ubiquitination. Src downregulation reduced OTUB1 and p27 expression, suggesting that IFNγ-induced cell cycle arrest is mediated by the Src-OTUB1-p27 signaling pathway. Our findings highlight the pivotal role of OTUB1 in IFNγ-induced p27 expression and cell cycle arrest, offering therapeutic implications.
Contrast enhanced ultrasound for traumatic spinal cord injury: an overview of current and future applications
Authors: Saway Brian Fabian , Courtney James , Barley Jessica , Frankel Bruce , Hofstetter Christoph , Kalhorn Stephen
Published: April 2024

Study design

Systematic review.

Objective

Contrast-enhanced ultrasound (CEUS) is an imaging modality that has only recently seen neurosurgical application. CEUS uses inert microbubbles to intraoperatively visualize vasculature and perfusion of the brain and spinal cord in real time. Observation and augmentation of spinal cord perfusion is vital component of the management of traumatic spinal cord injury, yet there are limited imaging modalities to evaluate spinal cord perfusion. CEUS provides an intraoperative imaging tool to evaluate spinal cord perfusion in real time. The objective of this review is to evaluate the current literature on the various applications and benefits of CEUS in traumatic spinal cord injury.

Setting

South Carolina, USA.

Methods

This review was written according to the PRISMA 2020 guidelines.

Results

143 articles were found in our literature search, with 46 of them being unique. After excluding articles for relevance to CEUS and spinal cord injury, we were left with 10 papers. Studies in animal models have shown CEUS to be an effective non-invasive imaging modality that can detect perfusion changes of injured spinal cords in real time.

Conclusion

This imaging modality can provide object perfusion data of the nidus of injury, surrounding penumbra and healthy neural tissue in a traumatized spinal cord. Investigation in its use in humans is ongoing and remains promising to be an effective diagnostic and prognostic tool for those suffering from spinal cord injury.
First-line oxaliplatin-based chemotherapy and nivolumab for metastatic microsatellite-stable colorectal cancer—the randomised METIMMOX trial
Authors: Ree Anne Hansen , Šaltytė Benth Jūratė , Hamre Hanne M. , Kersten Christian , Hofsli Eva , Guren Marianne G. , Sorbye Halfdan , Johansen Christin , Negård Anne , Bjørnetrø Tonje , Nilsen Hilde L. , Berg Jens P. , Flatmark Kjersti , Meltzer Sebastian
Published: April 2024

Background

We evaluated first-line treatment of metastatic microsatellite-stable colorectal cancer with short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade.

Methods

Patients were randomly assigned to chemotherapy (the FLOX regimen; control group) or alternating two cycles each of FLOX and nivolumab (experimental group). Radiographic response assessment was done every eight weeks with progression-free survival (PFS) as the primary endpoint. Cox proportional-hazards regression models estimated associations between PFS and relevant variables. A post hoc analysis explored C-reactive protein as signal of responsiveness to immune checkpoint blockade.

Results

Eighty patients were randomised and 38 in each group received treatment. PFS was comparable—control group: median 9.2 months (95% confidence interval (CI), 6.3–12.7); experimental group: median 9.2 months (95% CI, 4.5–15.0). The adjusted Cox model revealed that experimental-group subjects aged ≥60 had significantly lowered progression risk (p = 0.021) with hazard ratio 0.17 (95% CI, 0.04–0.76). Experimental-group patients with C-reactive protein <5.0 mg/L when starting nivolumab (n = 17) reached median PFS 15.8 months (95% CI, 7.8–23.7). One-sixth of experimental-group cases (all KRAS/BRAF-mutant) achieved complete response.

Conclusions

The investigational regimen did not improve the primary outcome for the intention-to-treat population but might benefit small subgroups of patients with previously untreated, metastatic microsatellite-stable colorectal cancer.

Trial registration

ClinicalTrials.gov number, NCT03388190 (02/01/2018).
Emerging roles of circular RNAs in nasopharyngeal carcinoma: functions and implications
Authors: Ma Aiyu , Yang Yuzhong , Lu Lu , Zhang Yan , Zhang Xuemei , Zheng Jinhua , Zheng Xiang
Published: April 2024

Nasopharyngeal carcinoma (NPC) is a distinct malignancy primarily prevalent in Southern China and Southeast Asia. Circular RNAs (circRNAs), a class of non-coding RNAs, are evolutionarily conserved and exhibit remarkable stability. Their dysregulation has been observed in various cancers, including NPC. In this review, we investigate the pivotal role of circRNAs in NPC, focusing specifically on their involvement in tumor proliferation, apoptosis, metastasis, angiogenesis, stemness, metabolism, and the tumor microenvironment. We highlight the diagnostic and prognostic potential of circRNAs in NPC, emphasizing their utility as biomarkers for early detection, disease monitoring, and prediction of treatment outcomes. Additionally, we explore the therapeutic implications of circRNAs in NPC, highlighting their potential for targeted therapies.
SARS-CoV-2 and its ORF3a, E and M viroporins activate inflammasome in human macrophages and induce of IL-1α in pulmonary epithelial and endothelial cells
Authors: Ambrożek-Latecka Magdalena , Kozlowski Piotr , Hoser Grażyna , Bandyszewska Magdalena , Hanusek Karolina , Nowis Dominika , Gołąb Jakub , Grzanka Małgorzata , Piekiełko-Witkowska Agnieszka , Schulz Luise , Hornung Franziska , Deinhardt-Emmer Stefanie , Kozlowska Ewa , Skirecki Tomasz
Published: April 2024

Inflammasome assembly is a potent mechanism responsible for the host protection against pathogens, including viruses. When compromised, it can allow viral replication, while when disrupted, it can perpetuate pathological responses by IL-1 signaling and pyroptotic cell death. SARS-CoV-2 infection was shown to activate inflammasome in the lungs of COVID-19 patients, however, potential mechanisms responsible for this response are not fully elucidated. In this study, we investigated the effects of ORF3a, E and M SARS-CoV-2 viroporins in the inflammasome activation in major populations of alveolar sentinel cells: macrophages, epithelial and endothelial cells. We demonstrated that each viroporin is capable of activation of the inflammasome in macrophages to trigger pyroptosis-like cell death and IL-1α release from epithelial and endothelial cells. Small molecule NLRP3 inflammasome inhibitors reduced IL-1 release but weakly affected the pyroptosis. Importantly, we discovered that while SARS-CoV-2 could not infect the pulmonary microvascular endothelial cells it induced IL-1α and IL-33 release. Together, these findings highlight the essential role of macrophages as the major inflammasome-activating cell population in the lungs and point to endothelial cell expressed IL-1α as a potential novel component driving the pulmonary immunothromobosis in COVID-19.
Multi-level, forming and filament free, bulk switching trilayer RRAM for neuromorphic computing at the edge
Authors: Park Jaeseoung , Kumar Ashwani , Zhou Yucheng , Oh Sangheon , Kim Jeong-Hoon , Shi Yuhan , Jain Soumil , Hota Gopabandhu , Qiu Erbin , Nagle Amelie L. , Schuller Ivan K. , Schuman Catherine D. , Cauwenberghs Gert , Kuzum Duygu
Published: April 2024

CMOS-RRAM integration holds great promise for low energy and high throughput neuromorphic computing. However, most RRAM technologies relying on filamentary switching suffer from variations and noise, leading to computational accuracy loss, increased energy consumption, and overhead by expensive program and verify schemes. We developed a filament-free, bulk switching RRAM technology to address these challenges. We systematically engineered a trilayer metal-oxide stack and investigated the switching characteristics of RRAM with varying thicknesses and oxygen vacancy distributions to achieve reliable bulk switching without any filament formation. We demonstrated bulk switching at megaohm regime with high current nonlinearity, up to 100 levels without compliance current. We developed a neuromorphic compute-in-memory platform and showcased edge computing by implementing a spiking neural network for an autonomous navigation/racing task. Our work addresses challenges posed by existing RRAM technologies and paves the way for neuromorphic computing at the edge under strict size, weight, and power constraints.
Iron-catalyzed stereoselective C–H alkylation for simultaneous construction of C–N axial and C-central chirality
Authors: Zhang Zi-Jing , Jacob Nicolas , Bhatia Shilpa , Boos Philipp , Chen Xinran , DeMuth Joshua C. , Messinis Antonis M. , Jei Becky Bongsuiru , Oliveira João C. A. , Radović Aleksa , Neidig Michael L. , Wencel-Delord Joanna , Ackermann Lutz
Published: April 2024

The assembly of chiral molecules with multiple stereogenic elements is challenging, and, despite of indisputable advances, largely limited to toxic, cost-intensive and precious metal catalysts. In sharp contrast, we herein disclose a versatile C–H alkylation using a non-toxic, low-cost iron catalyst for the synthesis of substituted indoles with two chiral elements. The key for achieving excellent diastereo- and enantioselectivity was substitution on a chiral N-heterocyclic carbene ligand providing steric hindrance and extra represented by noncovalent interaction for the concomitant generation of C–N axial chirality and C-stereogenic center. Experimental and computational mechanistic studies have unraveled the origin of the catalytic efficacy and stereoselectivity.
Denaturing mass photometry for rapid optimization of chemical protein-protein cross-linking reactions
Authors: Gizardin-Fredon Hugo , Santo Paulo E. , Chagot Marie-Eve , Charpentier Bruno , Bandeiras Tiago M. , Manival Xavier , Hernandez-Alba Oscar , Cianférani Sarah
Published: April 2024

Chemical cross-linking reactions (XL) are an important strategy for studying protein-protein interactions (PPIs), including low abundant sub-complexes, in structural biology. However, choosing XL reagents and conditions is laborious and mostly limited to analysis of protein assemblies that can be resolved using SDS-PAGE. To overcome these limitations, we develop here a denaturing mass photometry (dMP) method for fast, reliable and user-friendly optimization and monitoring of chemical XL reactions. The dMP is a robust 2-step protocol that ensures 95% of irreversible denaturation within only 5 min. We show that dMP provides accurate mass identification across a broad mass range (30 kDa–5 MDa) along with direct label-free relative quantification of all coexisting XL species (sub-complexes and aggregates). We compare dMP with SDS-PAGE and observe that, unlike the benchmark, dMP is time-efficient (3 min/triplicate), requires significantly less material (20–100×) and affords single molecule sensitivity. To illustrate its utility for routine structural biology applications, we show that dMP affords screening of 20 XL conditions in 1 h, accurately identifying and quantifying all coexisting species. Taken together, we anticipate that dMP will have an impact on ability to structurally characterize more PPIs and macromolecular assemblies, expected final complexes but also sub-complexes that form en route.
Deep learning the cis-regulatory code for gene expression in selected model plants
Authors: Peleke Fritz Forbang , Zumkeller Simon Maria , Gültas Mehmet , Schmitt Armin , Szymański Jędrzej
Published: April 2024

Elucidating the relationship between non-coding regulatory element sequences and gene expression is crucial for understanding gene regulation and genetic variation. We explored this link with the training of interpretable deep learning models predicting gene expression profiles from gene flanking regions of the plant species Arabidopsis thaliana, Solanum lycopersicum, Sorghum bicolor, and Zea mays. With over 80% accuracy, our models enabled predictive feature selection, highlighting e.g. the significant role of UTR regions in determining gene expression levels. The models demonstrated remarkable cross-species performance, effectively identifying both conserved and species-specific regulatory sequence features and their predictive power for gene expression. We illustrated the application of our approach by revealing causal links between genetic variation and gene expression changes across fourteen tomato genomes. Lastly, our models efficiently predicted genotype-specific expression of key functional gene groups, exemplified by underscoring known phenotypic and metabolic differences between Solanum lycopersicum and its wild, drought-resistant relative, Solanum pennellii.
Ambient carbon dioxide concentration correlates with SARS-CoV-2 aerostability and infection risk
Authors: Haddrell Allen , Oswin Henry , Otero-Fernandez Mara , Robinson Joshua F. , Cogan Tristan , Alexander Robert , Mann Jamie F. S. , Hill Darryl , Finn Adam , Davidson Andrew D. , Reid Jonathan P.
Published: April 2024

An improved understanding of the underlying physicochemical properties of respiratory aerosol that influence viral infectivity may open new avenues to mitigate the transmission of respiratory diseases such as COVID-19. Previous studies have shown that an increase in the pH of respiratory aerosols following generation due to changes in the gas-particle partitioning of pH buffering bicarbonate ions and carbon dioxide is a significant factor in reducing SARS-CoV-2 infectivity. We show here that a significant increase in SARS-CoV-2 aerostability results from a moderate increase in the atmospheric carbon dioxide concentration (e.g. 800 ppm), an effect that is more marked than that observed for changes in relative humidity. We model the likelihood of COVID-19 transmission on the ambient concentration of CO2, concluding that even this moderate increase in CO2 concentration results in a significant increase in overall risk. These observations confirm the critical importance of ventilation and maintaining low CO2 concentrations in indoor environments for mitigating disease transmission. Moreover, the correlation of increased CO2 concentration with viral aerostability need to be better understood when considering the consequences of increases in ambient CO2 levels in our atmosphere.
Photobody formation spatially segregates two opposing phytochrome B signaling actions of PIF5 degradation and stabilization
Authors: Kim Ruth Jean Ae , Fan De , He Jiangman , Kim Keunhwa , Du Juan , Chen Meng
Published: April 2024

Photoactivation of the plant photoreceptor and thermosensor phytochrome B (PHYB) triggers its condensation into subnuclear membraneless organelles named photobodies (PBs). However, the function of PBs in PHYB signaling remains frustratingly elusive. Here, we found that PHYB recruits PHYTOCHROME-INTERACTING FACTOR 5 (PIF5) to PBs. Surprisingly, PHYB exerts opposing roles in degrading and stabilizing PIF5. Perturbing PB size by overproducing PHYB provoked a biphasic PIF5 response: while a moderate increase in PHYB enhanced PIF5 degradation, further elevating the PHYB level stabilized PIF5 by retaining more of it in enlarged PBs. Conversely, reducing PB size by dim light, which enhanced PB dynamics and nucleoplasmic PHYB and PIF5, switched the balance towards PIF5 degradation. Together, these results reveal that PB formation spatially segregates two antagonistic PHYB signaling actions – PIF5 stabilization in PBs and PIF5 degradation in the surrounding nucleoplasm – which could enable an environmentally sensitive, counterbalancing mechanism to titrate nucleoplasmic PIF5 and environmental responses.
Cross-modality mapping using image varifolds to align tissue-scale atlases to molecular-scale measures with application to 2D brain sections
Authors: Stouffer Kaitlin M. , Trouvé Alain , Younes Laurent , Kunst Michael , Ng Lydia , Zeng Hongkui , Anant Manjari , Fan Jean , Kim Yongsoo , Chen Xiaoyin , Rue Mara , Miller Michael I.
Published: April 2024

This paper explicates a solution to building correspondences between molecular-scale transcriptomics and tissue-scale atlases. This problem arises in atlas construction and cross-specimen/technology alignment where specimens per emerging technology remain sparse and conventional image representations cannot efficiently model the high dimensions from subcellular detection of thousands of genes. We address these challenges by representing spatial transcriptomics data as generalized functions encoding position and high-dimensional feature (gene, cell type) identity. We map onto low-dimensional atlas ontologies by modeling regions as homogeneous random fields with unknown transcriptomic feature distribution. We solve simultaneously for the minimizing geodesic diffeomorphism of coordinates through LDDMM and for these latent feature densities. We map tissue-scale mouse brain atlases to gene-based and cell-based transcriptomics data from MERFISH and BARseq technologies and to histopathology and cross-species atlases to illustrate integration of diverse molecular and cellular datasets into a single coordinate system as a means of comparison and further atlas construction.
Collapse of carbon nanotubes due to local high-pressure from van der Waals encapsulation
Authors: Hu Cheng , Chen Jiajun , Zhou Xianliang , Xie Yufeng , Huang Xinyue , Wu Zhenghan , Ma Saiqun , Zhang Zhichun , Xu Kunqi , Wan Neng , Zhang Yueheng , Liang Qi , Shi Zhiwen
Published: April 2024

Van der Waals (vdW) assembly of low-dimensional materials has proven the capability of creating structures with on-demand properties. It is predicted that the vdW encapsulation can induce a local high-pressure of a few GPa, which will strongly modify the structure and property of trapped materials. Here, we report on the structural collapse of carbon nanotubes (CNTs) induced by the vdW encapsulation. By simply covering CNTs with a hexagonal boron nitride flake, most of the CNTs (≈77%) convert from a tubular structure to a collapsed flat structure. Regardless of their original diameters, all the collapsed CNTs exhibit a uniform height of ≈0.7 nm, which is roughly the thickness of bilayer graphene. Such structural collapse is further confirmed by Raman spectroscopy, which shows a prominent broadening and blue shift in the Raman G-peak. The vdW encapsulation-induced collapse of CNTs is fully captured by molecular dynamics simulations of the local vdW pressure. Further near-field optical characterization reveals a metal-semiconductor transition in accompany with the CNT structural collapse. Our study provides not only a convenient approach to generate local high-pressure for fundamental research, but also a collapsed-CNT semiconductor for nanoelectronic applications.
Empowering high-dimensional optical fiber communications with integrated photonic processors
Authors: Lu Kaihang , Chen Zengqi , Chen Hao , Zhou Wu , Zhang Zunyue , Tsang Hon Ki , Tong Yeyu
Published: April 2024

Mode-division multiplexing (MDM) in optical fibers enables multichannel capabilities for various applications, including data transmission, quantum networks, imaging, and sensing. However, high-dimensional optical fiber systems, usually necessity bulk-optics approaches for launching different orthogonal fiber modes into the optical fiber, and multiple-input multiple-output digital electronic signal processing at the receiver to undo the arbitrary mode scrambling introduced by coupling and transmission in a multi-mode fiber. Here we show that a high-dimensional optical fiber communication system can be implemented by a reconfigurable integrated photonic processor, featuring kernels of multichannel mode multiplexing transmitter and all-optical descrambling receiver. Effective mode management can be achieved through the configuration of the integrated optical mesh. Inter-chip MDM optical communications involving six spatial- and polarization modes was realized, despite the presence of unknown mode mixing and polarization rotation in the circular-core optical fiber. The proposed photonic integration approach holds promising prospects for future space-division multiplexing applications.
Subgroup analyses from the phase 3 ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer
Authors: Hurvitz Sara A. , Bardia Aditya , Punie Kevin , Kalinsky Kevin , Carey Lisa A. , Rugo Hope S. , Diéras Véronique , Phan See , Delaney Rosemary , Zhu Yanni , Tolaney Sara M.
Published: April 2024

In this post hoc analysis of the ASCENT study, we compared outcomes with sacituzumab govitecan (SG) vs single-agent chemotherapy in clinically important subgroups of patients with metastatic triple-negative breast cancer (mTNBC). Patients with mTNBC refractory to/relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG or treatment of physician’s choice (TPC) until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) per RECIST 1.1 by central review in patients without brain metastases. Patients with brain metastases were allowed if metastases were stable ≥4 weeks. In the intention-to-treat (ITT) population, 19% of patients were age ≥65 years; 12% were Black, and 12% had brain metastases. SG improved PFS and overall survival (OS), respectively, vs TPC in patients age ≥65 years (7.1 vs 2.4 months and 14.7 vs 8.9 months), or of Black race (5.4 vs 2.2 months and 13.8 vs 8.5 months), consistent with outcomes in the ITT population. Patients with brain metastases had numerically higher median PFS with SG vs TPC, but median OS was similar between treatment groups. SG was well tolerated and had a manageable safety profile consistent with the full safety population across all subgroups; neutropenia and diarrhea were the most common treatment-emergent adverse events. These findings confirm the meaningful clinical benefit of SG vs standard chemotherapy in patient subgroups with high unmet needs. SG should be considered an effective and safe treatment option for patients with mTNBC eligible for second-line or later therapy. ClinicalTrials.gov Number: NCT02574455.
Passivation and corrosion of Al current collectors in lithium-ion batteries
Authors: Du Pin , Wan Jiale , Qu Jiakang , Xie Hongwei , Wang Dihua , Yin Huayi
Published: April 2024

State-of-the-art lithium-ion batteries inevitably suffer from electrode corrosion over long-term operation, such as corrosion of Al current collectors. However, the understanding of Al corrosion and its impacts on the battery performances have not been evaluated in detail. The passivation, its breakdown, and corrosion of the Al resulted in the deterioration of the solid/solid interface and electrode integrity. Additionally, localized diffusion of F−/Al3+ brought the irreversible current detrimental to the Coulomb efficiency (1.14% loss). Eventually, the behavior led to extensive capacity damage (>20%) to battery performance until lifespan. During the battery cycling, the passivation layer greater than 20 nm was generated near the median voltage. When the charging voltage rose, the passivation layer was squeezed and deformed by the newly generated Al-F-O particles, resulting in stress corrosion cracks. The passivation layer peeled off, and the nano-passivation layer material was re-generated as the voltage continued to rise. The above results were repeated, and the Al matrix was continuously consumed. The passivity breakdown with localized corrosion was derived from ethylene carbonate adsorption, which was highly correlated to the charge voltages, especially at 4.4 V and 4.8 V. The results will serve as a benchmark for electrode corrosion of other advanced energy storage materials, which is crucial for electrode engineering and performance modulation using interfacial design.