bluuebunny/crossref_metadata_2025 huggingface dataset:
Cladribine tablets in Relapsing-Remitting Multiple Sclerosis preferentially target B-cells
Authors: Ammoscato Francesca , Aboulwafa Mohammad , Skonieczna Justyna , Bestwick Jonathan , Monero Rosemary , Andrews Michael , Trane Stefania De , Holden David , Adams Ashok , Bianchi Lucia , Turner Ben , Marta Monica , Schmierer Klaus , Baker David , Giovannoni Gavin , Gnanapavan Sharmilee
Published: March 2024

Recently it has been shown that treatments targeting B cells in multiple sclerosis (MS) are effective in controlling disease activity. B cells contribute to the pathogenesis of MS via antigen presentation, T cell activation, and antibody production. In the chronic progressive cladribine trial, some patients treated with cladribine had a significant decline in oligoclonal band number. However, the mode of action of cladribine tablets (CladT) on peripheral immune cells and its biological activity within the CNS remains to be determined further.

The CladB study is a longitudinal prospective investigation of CladT treatment in relapsing-remitting MS (RRMS). Blood was sampled at Day 0, 1, 5, then once a week for 8 weeks, fortnightly up to 24 weeks, and once a month till 96 weeks for immune cells. This was compared to a historical cohort of alemtuzumab treated samples for one month. Paired cerebrospinal fluid (CSF) and blood were also taken at Day 0, 48 and 96 weeks after initiating CladT for Kappa and Lambda-free light chain (кFLC, λFLC) index, oligoclonal bands (OCBs), immunoglobulin indices, inflammatory mediators and neurofilament light chain (NfL). Participants also underwent clinical and magnetic resonance imaging brain assessments.

Ten participants (3 male, 7 female, mean age 35.9 ± 10.5 (SD) and Expanded disability Status Scale 2.5 (range 0-6) at baseline were enrolled. B cells, in particular memory B cells, were heavily depleted by CladT. Alemtuzumab, conversely rapidly depleted both T and B cells. Although still present, reduction in OCB numbers were observed in 4/10 participants and кFLC index reduced from mean 164.5 ± 227.1 (SD) at baseline to 71.3 ± 84.7 at 48 weeks (p=0.002) and 64.4 ± 67.3 at 96 weeks (p=0.01). This coincided with reduction in IgG index [1.1 ± 0.5 (SD) at baseline, 0.8 ± 0.4 (p=0.014) at 48 weeks and 0.8 ± 0.3 (P=0.02) at 96 weeks] and CSF CXCL-13 [88.6± 68.4 (SD) pg/mL, 39.4 ± 35.2 mg/mL (p=0.037) at 48 weeks and 19.1 ± 11.7pg/ml at 96 weeks (p=0.027)]. CSF NfL levels were reduced at 48 weeks only (p=0.01).

In conclusion, our study supports the view that CladT treatment works primarily by depleting memory B-cells and antibody-secreting cell precursors in RRMS leading to sustained effects on intrathecal antibody production and total IgG associated with a reduction in the B-cell chemoattractant CXCL-13 in the CSF.
Inequalities in behavioural risk factor prevalence between five post-war generational cohorts of working age, England
Authors: Bajekal Madhavi , Scholes Shaun
Published: March 2024

Background and objectives

Long-term trends in health risk factor prevalence, and in inequalities, are often summarised using age-standardised point prevalence to allow for age distribution changes over time and between groups. Policies to effectively promote health require the decomposition of social change into its age-period-cohort components. As a first step, we provide a descriptive age-cohort analysis to identify patterns of generational change in key behavioural risk factors between and within post-war cohorts of working age in England.

Data

Cross-sectional Health Survey for England data for participants aged 25-60 years was pooled between 1994-2019 (n=153,172) to construct five decennial cohorts (1940s, 1950s, 1960s, 1970s, 1980s). Socioeconomic status was classified by neighbourhood deprivation quintiles using the Index of Multiple Deprivation. Five behavioural risk factors were analysed: cigarette smoking (current-and heavy-smoking); alcohol consumption (frequency and heavy drinking); obesity; meeting recommended levels of physical activity and fruit and vegetables consumption.

Methods

Sex-specific analyses were conducted. Log-binomial regression models quantified the magnitude and direction of change in (i) prevalence ratios (PRs) between cohorts adjusting for age and deprivation and (ii) deprivation-specific PRs within- and between-cohorts to examine changes in absolute and relative inequalities between generations.

Results

In more recent cohorts, decreases in prevalence, independent of age and deprivation, were observed for current smoking, frequency of alcohol consumption and heavy drinking, resulting in decreasing absolute inequalities. However, obesity levels, particularly among females, reached their highest levels in the youngest 1980s cohort.

Relative inequalities in current smoking (most-versus least-deprived quintiles) peaked in the 1950s cohort (Males: PR 2.79 (95% CI:2.57-3.04); Females: PR 2.81; 95% CI: 2.60-3.05)), decreased in the 1960s cohort (M: PR 2.00 (95% CI:1.70-2.34); F: PR 2.58 (95% CI:2.40-2.77)), and remained stable thereafter. Inequalities in heavy smoking persisted over time among current smokers.

Higher obesity levels in the most-versus least-deprived quintiles were generally persistent across all five cohorts, albeit with some suggestion of widening inequalities in the younger-versus older-cohorts in females (1940s cohort: PR 1.55 (95% CI:1.40-1.72); 1960s cohort: PR 1.87 (95% CI: 1.73-2.01)). This pattern was also observed for mean body mass index (BMI).

For heavy drinking, relative inequality remained stable. Relative inequalities in fruit and vegetable consumption were lower in more recent cohorts. Physical activity levels were similar across cohorts, with little evidence of inequalities.

Conclusion

Our analysis of generational change reveals credible signals of behavioural risk factor changes in levels and in inequalities over successive post-war cohorts of working age.
Applications of Large Language Models in Psychiatry: A Systematic Review
Authors: Omar Mahmud , Soffer Shelly , Charney Alexander W , Landi Isotta , Nadkarni Girish N , Klang Eyal
Published: March 2024

Background

With their unmatched ability to interpret and engage with human language and context, large language models (LLMs) hint at the potential to bridge AI and human cognitive processes. This review explores the current application of LLMs, such as ChatGPT, in the field of psychiatry.

Methods

We followed PRISMA guidelines and searched through PubMed, Embase, Web of Science, and Scopus, up until March 2024.

Results

From 771 retrieved articles, we included 16 that directly examine LLMs’ use in psychiatry. LLMs, particularly ChatGPT and GPT-4, showed diverse applications in clinical reasoning, social media, and education within psychiatry. They can assist in diagnosing mental health issues, managing depression, evaluating suicide risk, and supporting education in the field. However, our review also points out their limitations, such as difficulties with complex cases and potential underestimation of suicide risks.

Conclusion

Early research in psychiatry reveals LLMs’ versatile applications, from diagnostic support to educational roles. Given the rapid pace of advancement, future investigations are poised to explore the extent to which these models might redefine traditional roles in mental health care.
Assessing Post-TAVR Cardiac Conduction Abnormalities Risk Using a Digital Twin of a Beating Heart
Authors: Reza Symon , Kovarovic Brandon , Bluestein Danny
Published: March 2024

Transcatheter aortic valve replacement (TAVR) has rapidly displaced surgical aortic valve replacement (SAVR). However, certain post-TAVR complications persist, with cardiac conduction abnormalities (CCA) being one of the major ones. The elevated pressure exerted by the TAVR stent onto the conduction fibers situated between the aortic annulus and the His bundle, in proximity to the atrioventricular (AV) node, may disrupt the cardiac conduction leading to the emergence of CCA. In his study, anin-silicoframework was developed to assess the CCA risk, incorporating the effect of a dynamic beating heart and pre-procedural parameters such as implantation depth and preexisting cardiac asynchrony in the new onset of post-TAVR CCA. A self-expandable TAVR device deployment was simulated inside an electro-mechanically coupled beating heart model in five patient scenarios, including three implantation depths, and two preexisting cardiac asynchronies: (i) a right bundle branch block (RBBB) and (ii) a left bundle branch block (LBBB). Subsequently, several biomechanical parameters were analyzed to assess the post-TAVR CCA risk. The results manifested a lower cumulative contact pressure on the conduction fibers following TAVR for aortic deployment (0.018 MPa) compared to baseline (0.29 MPa) and ventricular deployment (0.52 MPa). Notably, the preexisting RBBB demonstrated a higher cumulative contact pressure (0.34 MPa) compared to the baseline and preexisting LBBB (0.25 MPa). Deeper implantation and preexisting RBBB cause higher stresses and contact pressure on the conduction fibers leading to an increased risk of post-TAVR CCA. Conversely, implantation above the MS landmark and preexisting LBBB reduces the risk.
Acute and Longitudinal Effects of Sport-related Concussion on Reactive Balance
Authors: Monoli Cecilia , Morris Amanda , Crofts Regan , Fino Nora F. , Petersell Tessa L. , Jameson Trevor , Dibble Leland E. , Fino Peter C.
Published: March 2024

Postural instability is a common observation after concussions, with balance assessments playing a crucial role in clinical evaluations. Widely used post-concussion balance tests focus primarily on static and dynamic balance, excluding the critical aspect of reactive balance. This study investigated the acute and longitudinal effects of concussion on reactive balance in collegiate athletes. The assessments were conducted at pre-season baseline and 4 post-concussion timepoints: acute, pre-return-to-play, post-return-to-play, and six months post-concussion. The instrumented-modified Push and Release test measured reactive balance. Longitudinal effects of concussions on time to stability and step latency metrics were investigated applying Generalized Estimating Equations. Acutely after concussion, athletes demonstrated impaired reactive balance, indicated by longer times to stability, in dual-task conditions (p= 0.004). These acute impairments were transient and recovered over time. Exploratory analyses revealed that athletes who sustained their first lifetime concussion exhibited both acute (p= 0.037) and longitudinal (p= 0.004 at post-return-to-play) impairments in single– and dual-task compared to controls with no lifetime concussion. This comprehensive evaluation provides insights into the multifaceted nature of post-concussion impairments and emphasizes the importance of considering cognitive demand and history of concussions in assessing athletes’ balance.
Effectiveness of Autumn 2023 COVID-19 vaccination and residual protection of prior doses against hospitalisation in England, estimated using a test-negative case-control study
Authors: Møller Kirsebom Freja Cordelia , Stowe Julia , Bernal Jamie Lopez , Allen Alex , Andrews Nick
Published: March 2024

Introduction

The last COVID-19 vaccine offered to all adults in England became available from November 2021. The most recent booster programme commenced in September 2023. Bivalent BA.4-5 or monovalent XBB.1.5 boosters were given. During the study period, the JN.1 variant became dominant in England.

Methods

Vaccine effectiveness against hospitalisation was estimated throughout using the test-negative case-control study design where positive PCR tests from hospitalised individuals are cases and comparable negative PCR tests are controls. Multivariable logistic regression was used to assess vaccine effectiveness against hospitalisation with the test result as the outcome, vaccination status as the primary exposure variable of interest and confounder adjustment.

Results

There was no evidence of residual protection for boosters given as part of previous campaigns. There were 28,916 eligible tests included to estimate the effectiveness of the autumn 2023 boosters in those aged 65 years and older. VE peaked at 50.6% (95% CI: 44.2-56.3%) after 2-4 weeks, followed by waning to 13.6% (95% CI: -11.7-33.2%). Estimates were generally higher for the XBB.1.5 booster than the BA.4-5 booster, but this difference was not statistically significant. Point estimates were highest against XBB sub-lineages. Effectiveness was lower against both JN.1 and EG.5.1 variants with confidence intervals non-overlapping with the effectiveness of the XBB sub-lineages at 2-4 weeks for EG.5.1 where VE was 44.5% (95% CI: 20.2-61.4%) and at 5-9 weeks for JN.1 where VE was 26.4% (95%CI: -3.4-47.6%).

Conclusions

The recent monovalent XBB.1.5 and bivalent BA.4-5 boosters provided comparable and good protection against hospitalisation, however there was evidence of lower VE against hospitalisation of these boosters against JN.1.
Nuclear blebs are associated with destabilized chromatin packing domains
Authors: Pujadas Liwag Emily M. , Acosta Nicolas , Almassalha Luay Matthew , Su Yuanzhe (Patrick) , Gong Ruyi , Kanemaki Masato T. , Stephens Andrew D. , Backman Vadim
Published: March 2024

Disrupted nuclear shape is associated with multiple pathological processes including premature aging disorders, cancer-relevant chromosomal rearrangements, and DNA damage. Nuclear blebs (i.e., herniations of the nuclear envelope) have been induced by (1) nuclear compression, (2) nuclear migration (e.g., cancer metastasis), (3) actin contraction, (4) lamin mutation or depletion, and (5) heterochromatin enzyme inhibition. Recent work has shown that chromatin transformation is a hallmark of bleb formation, but the transformation of higher-order structures in blebs is not well understood. As higher-order chromatin has been shown to assemble into nanoscopic packing domains, we investigated if (1) packing domain organization is altered within nuclear blebs and (2) if alteration in packing domain structure contributed to bleb formation. Using Dual-Partial Wave Spectroscopic microscopy, we show that chromatin packing domains within blebs are transformed both by B-type lamin depletion and the inhibition of heterochromatin enzymes compared to the nuclear body. Pairing these results with single-molecule localization microscopy of constitutive heterochromatin, we show fragmentation of nanoscopic heterochromatin domains within bleb domains. Overall, these findings indicate that translocation into blebs results in a fragmented higher-order chromatin structure.

SUMMARY STATEMENT

Nuclear blebs are linked to various pathologies, including cancer and premature aging disorders. We investigate alterations in higher-order chromatin structure within blebs, revealing fragmentation of nanoscopic heterochromatin domains.
Quantify genetic variants' regulatory potential via a hybrid sequence-oriented model
Authors: Wang Yu , Liang Nan , Gao Ge
Published: April 2024

Understanding how noncoding DNA determines gene expression is critical for decoding the functional genome. Leveraging a hybrid sequence-oriented architecture, we developed SVEN to model (and predict) tissue-specific transcriptomic impacts for large-scale structural variants across over 200 tissues and cell lines. We expect that SVEN will enable more effective in silico analysis and interpretation of human genome-wide disease-related genetic variants.
Intrinsically disordered region amplifies membrane remodeling to augment selective ER-phagy
Authors: Poveda-Cuevas Sergio Alejandro , Lohachova Kateryna , Dikic Ivan , Hummer Gerhard , Bhaskara Ramachandra M.
Published: March 2024

Intrinsically disordered regions (IDRs) play a pivotal role in organellar remodeling. They transduce signals across membranes, scaffold signaling complexes, and mediate vesicular traffic. Their functions are regulated by constraining conformational ensembles through specific intra- and inter-molecular interactions, physical tethering, and post-translational modifications. The ER-phagy receptor FAM134B/RETREG1, known for its Reticulon homology domain (RHD), includes a substantial C-terminal intrinsically disorder region (IDR) housing the LC3 interacting (LIR) motif. Beyond engaging the autophagic machinery, the function of the FAM134B-IDR is unclear. Here, we investigate the characteristics of the FAM134B-IDR by extensive modeling and molecular dynamics (MD) simulations. We present detailed structural models for the IDR, mapping its conformational landscape in solution and membrane-anchored configurations. Our analysis reveals that depending on the membrane anchor, the IDRs collapse onto the membrane and induce positive membrane curvature to varying degrees. The charge patterns underlying this Janus-like behavior are conserved across other ER-phagy receptors. We found that IDRs alone are sufficient to sense curvature. When combined with RHDs, they intensify membrane remodeling and drive efficient protein clustering, leading to faster budding, thereby amplifying RHD remodeling functions. Our simulations provide a new perspective on IDRs of FAM134B, their Janus-like membrane interactions, and the resulting modulatory functions during large-scale ER remodeling.
Single-Molecule Imaging Reveals the Mechanism of Bidirectional Replication Initiation in Metazoa
Authors: Terui Riki , Berger Scott , Sambel Larissa , Song Dan , Chistol Gheorghe
Published: March 2024

Metazoan genomes are copied bidirectionally from thousands of replication origins. Replication initiation entails the assembly and activation of two CMG (Cdc45•Mcm2-7•GINS) helicases at each origin. This requires several firing factors (including TopBP1, RecQL4, DONSON) whose exact roles remain unclear. How two helicases are correctly assembled and activated at every single origin is a long-standing question. By visualizing the recruitment of GINS, Cdc45, TopBP1, RecQL4, and DONSON in real time, we uncovered a surprisingly dynamic picture of initiation. Firing factors transiently bind origins but do not travel with replisomes. Two Cdc45 simultaneously arrive at each origin and two GINS are recruited together, even though neither protein can dimerize. The synchronized delivery of two GINS is mediated by DONSON, which acts as a dimerization scaffold. We show that RecQL4 promotes DONSON dissociation and facilitates helicase activation. The high fidelity of bidirectional origin firing can be explained by a Hopfield-style kinetic proofreading mechanism.
Construction of Animal Models Based on Exploring Pathological Features and Mechanisms of Different Locations in the Progression of DVT-APTE-CTEPD/CTEPH
Authors: Lin Qinghuang , Wang Wenfeng , Chen Xiaoyun , Liu Jixiang , Shao Nan , Wu Qiuxia , Lai Xingyue , Chen Maohe , Chen Min , Wu Yijin , Wu Dawen , Li Hongli , Yang Peiran , Zhang Yunxia , Zhang Zhu , Zhai Zhenguo , Deng Chaosheng
Published: March 2024

Background

Chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH) are sequelae of acute pulmonary embolism (APE) and severely affect patients’ health and quality of life. The treatment of these conditions is challenging, and their underlying mechanisms remain unclear. The main reason for this is the lack of an animal model that can fully simulate the entire chain of DVT-APTE-CTEPD/CTEPH progression. The objective of this study is to construct an ideal animal model that simulates the major pathological changes of DVT-APTE-CTEPD/CTEPH and can be used for mechanistic exploration. We aim to compare the advantages and disadvantages of different modeling approaches and provide an experimental basis for investigating the mechanisms of pulmonary embolism chronicization at different stages of evolution.

Methods and Materials

We first evaluated the pathological changes in the pulmonary arterial intima stripping tissue of CTEPH patients. Animal models were established by multiple injections of thrombus columns through the internal jugular vein to simulate distal remodeling of the pulmonary artery. To simulate significant remodeling and fibrosis in the middle and distal segments of the pulmonary artery, thrombus columns were injected along with splenectomy. A CTEPD model with intimal fibrosis remodeling was successfully established by selectively injecting large thromboemboli into the pulmonary artery sites in large animals (dogs). A rat model with pathological manifestations of intimal fibrosis remodeling in the proximal end of the pulmonary artery was constructed using large thrombi combined with nitric oxide synthase inhibitors. An animal model of DVT was established using the inferior vena cava ligation method.

Results

According to the different pathological features and mechanisms observed in the progression of human DVT-APTE-CTEPD/CTEPH, we constructed animal models that conform to these pathological manifestations and mechanisms, each with its own advantages. Furthermore, the different methods used to construct animal models can be integrated and applied together.

Conclusion

Animal models constructed using different modeling methods can effectively simulate the pathological and physiological manifestations of the corresponding stages of chronic pulmonary embolism. Researchers can select the aforementioned models according to their specific research purposes, directions, and requirements.
Immediate-Early Genes as Influencers in Genetic Networks and their Role in Alzheimer’s Disease
Authors: Zachariou Margarita , Loizidou Eleni M. , Spyrou George M.
Published: March 2024

Abstract/Summary

Immediate-early genes (IEGs) are a class of activity-regulated genes (ARGs) that are transiently and rapidly activated in the absence of de novo protein synthesis in response to neuronal activity. We explored the role of IEGs in genetic networks to pinpoint potential drug targets for Alzheimer’s disease (AD). Using a combination of network analysis and genome-wide association study (GWAS) summary statistics we show that (1) IEGs exert greater topological influence across different human and mouse gene networks compared to other ARGs, (2) ARGs are sparsely involved in diseases and significantly more mutational constrained compared to non-ARGs, (3) Many AD-linked variants are in ARGs gene regions, mainly inMARK4near FOSB, with an AD risk eQTL that increasesMARK4expression in cortical areas, (4)MARK4holds an influential place in a dense AD multi-omic network and a high AD druggability score. Our work on IEGs’ influential network role is a valuable contribution to guiding interventions for diseases marked by dysregulation of their downstream targets and highlightsMARK4as a promising underexplored AD-target.

Highlights

Immediate-early genes are topologically influential in brain genetic networks in mouse and human.

Activity-regulated Genes (ARGs) are highly constrained with sparse gene-disease relevance.

There are several AD-associated variants in ARGs gene regions, mainly inMARK4nearFOSB.

GWAS and network analysis of ARG’s pinpointMARK4as a promising underexplored AD target.
Tumour-derived extracellular vesicles within the therapy-induced senescent secretome distinctly suppress breast cancer via DKK1-mediated inflammatory response
Authors: Robert Matius , Jakhar Rekha , Au Bijin Veonice , Eng Gracie Wee Ling , Wei Meng , Gao Alvin Kunyao , Chuah You Heng , Sachaphibulkij Karishma , Bonne Isabelle , Lim Kah Jing , Sinha Indrajit , Teh Daniel Boon Leng , Lim Lina Hsiu Kim , Kumar Prashant , Verma Navin Kumar , Sze Newman Siu Kwan , Lim Elaine Hsuen , Ong Derrick Sek Tong , Cheong Jit Kong , Itahana Koji , Connolly John Edward , Crasta Karen Carmelina
Published: March 2024

Triple-negative breast cancers (TNBC), associated with poor prognosis and high tumour recurrence, are often-treated with taxanes in first-line treatment regimens. However, acquired disease resistance can often set in, hampering clinical efficacy. One avenue that could engender therapy resistance is therapy-induced senescence (TIS), as they represent a population of residual disease and are highly secretory. Although it is known that TIS can contribute to tumour development and therapy resistance via the therapy-induced secretome, the underlying molecular mechanisms are not fully understood. In this study, we sought to dissect the role of the TNBC-derived TIS-associated secretome in chemoresponse. We found that paclitaxel-treated cells induced mitotic slippage and entered senescence as tetraploid cells. The therapy-induced SASP was found to be enriched in soluble cytokines and other pro-tumorigenic factors linked to tumour recurrence and distant metastasis. Interestingly, we found that senescence-associated small extracellular vesicles (sEVs) or exosomes, an underappreciated component of SASP, increased genomic instability, ROS and anti-tumour activity. Exosomal proteomic and transcriptomic profiling further revealed DKK1, a negative regulator of WNT signalling, to be enriched in TIS-sEVs. Further investigation demonstrated DKK1-control of inflammatory cytokines production to confer reduced tumour activity in recipient TNBC cancer cells. Taken together, this study revealed unexpected findings where TIS-sEVs confer opposing tumourigenic outcomes to that elicited by TIS-SASP, indicating that sEVs should be considered as distinct SASP entities.
Parent-specific transgenerational immune priming enhances offspring defense – unless heat-stress negates it all
Authors: Schneider Ralf F , Dubin Arseny , Marten Silke-Mareike , Roth Olivia
Published: March 2024

Trans-generational immune priming (TGIP) adjusts offspring immune responses based on parental immunological experiences - a form of trans-generational plasticity predicted to be adaptive when parent-offspring environmental conditions match. In contrast, mis-matches between environmental conditions negate those advantages, rendering TGIP costly when mismatched immunological offspring phenotypes are induced. Particularly maternal TGIP was thought to shape offspring immunological preparedness: mothers’ eggs contain more substance than sperm and, in viviparous species, pregnancy provides additional avenues for immune priming of developing offspring. The syngnathids’ (pipefishes and seahorses) unique male pregnancy provides an unusual perspective to the ecological relevance of TGIP in a system where egg production and pregnancy occur in different sexes. We simulated parental bacteria exposure in broad nosed pipefish,Syngnathus typhle, through vaccinations with heat-killedVibrio aestuarianusbefore mating the fish to each other or control individuals. Resulting offspring were raised, and some exposed toV. aestuarianus, in a control or heat-stress environment, after which transcriptome and microbiome compositions were investigated. Transcriptomic TGIP effects were only observed inVibrio-exposed offspring at control temperatures, arguing for low costs of TGIP in non-matching environments. Transcriptomic phenotypes elicited by maternal and paternal TGIP had only limited overlap and were not additive. Both transcriptomic responses were significantly associated to immune functions, and specifically the paternal response to the innate immune branch. TGIP of both parents reduced the relative abundance of the experimentalVibrioin exposed offspring, showcasing its ecological effectiveness. Despite its significance in matching biotic environments, no TGIP-associated phenotypes were observed for heat-treated offspring. Heat-spikes caused by climate change thus threaten TGIP benefits, potentially increasing susceptibility to emerging marine diseases. This highlights the urgent need to understand how animals will cope with climate-induced changes in microbial assemblages by illustrating the importance – and limits - of TGIP in mitigating the impacts of environmental stressors on offspring vulnerability.
In quiescent G0 phase,Schizosaccharomyces pombeMis4 ensures full nuclear separation during the subsequent M phase
Authors: Suma Michiko , Arakawa Orie , Tahara Yuria , Sajiki Kenichi , Saitoh Shigeaki , Yanagida Mitsuhiro
Published: March 2024

Evolutionarily conserved Mis4 establishes cohesion between replicated sister chromatids in vegetatively proliferating cells. In the fission yeast,Schizosaccharomyces pombe, defects in Mis4 lead to premature separation of sister chromatids, resulting in fatal chromosome mis-segregation during mitosis. In humans, NIPBL, an ortholog of Mis4, is responsible for a severe multisystem disorder called Cornelia de Lange syndrome. We previously reported that Mis4 is also essential in non-proliferating quiescent cells. Whereas wild-type fission yeast cells can maintain high viability for long periods without cell division in the quiescent G0 phase,mis4-450mutant cells cannot. In this report, we show that Mis4 is not required for cells to enter G0 phase, but is essential to exit from it. When resuming mitosis after passage of G0,mis4mutant cells segregated sister chromatid successfully, but insufficiently separated daughter nuclei consequently formed dikaryon-like cells. These findings suggest a novel role of Mis4/NIPBL in non-dividing quiescent cells, which is prerequisite for full nuclear separation upon resumed mitosis. As most human cells are in the quiescent state, this study may facilitate development of novel therapies for human diseases caused by Mis4/NIPBL deficiency.
Temperature dependence of refractive indices of
InP
,
GaAs
,
AlAs
, and
In0.53Ga0.47As
in the midinfrared spectral range determined by combined ellipsometry and Fourier-transform spectroscopy
Authors: Mikulicz Monika , Smolka Tristan , Rygala Michal , Badura Mikolaj , Kijaszek Wojciech , Lozińska Adriana , Kamp Martin , Motyka Marcin
Published: April 2024

We present the results of Fourier-transform measurements for determination of refractive indices of four semiconductor alloys in the midinfrared spectral range from 10 to 300 K. We investigate double-sided-polished, undoped InP and GaAs substrates as well as In0.53Ga0.47As/InP and AlAs/GaAs distributed Bragg reflector (DBR) mirrors with their operational wavelength designed for 4 µm. Through analysis of measured transmittance spectra supported by ellipsometry it is possible to determine the temperature-dependent refractive indices of InP and GaAs from 1.3 to 11 µm. Furthermore, by using reflectivity measurements supported by numerical modeling of the two types of designed DBR structures the refractive indices of In0.53Ga0.47As and AlAs for around 4 µm are determined with their temperature dependencies. Data acquired through this method could lead to improvement of already existing optical semiconductor devices expanding their application for longer wavelengths.

Published by the American Physical Society
2024
Energy condensation and dipole alignment in protein dynamics
Authors: Tenenbaum Alexander
Published: April 2024

The possibility that distant biomolecules in a cell interact via electromagnetic (e.m.) radiation was proposed many years ago to explain the high rate of encounters of partners in some enzymatic reactions. The results of two recent experiments designed to test the propensity of protein bovine serum albumin (BSA) to interact via e.m. radiation with other proteins were interpreted in a theoretical framework based on three main assumptions: (i) in order to experience this kind of interaction the protein must be in an out-of-equilibrium state; (ii) in this state there is a condensation of energy in low-frequency vibrational modes; and (iii) the hydration layers of water around the protein sustain the energy condensation. In the present paper we present the results of molecular dynamics simulations of BSA in four states: at equilibrium and out-of-equilibrium in water, and at room and high temperature in vacuum. By comparing physical properties of the system in the four states, our simulations provide a qualitative and quantitative assessment of the three assumptions on which the theoretical framework is based. Our results confirm the assumptions of the theoretical model showing energy condensation at low frequency and electretlike alignment between the protein's and the water's dipoles; they also allow a quantitative estimate of the contribution of the out-of-equilibrium state and of the water to the observed behavior of the protein. In particular, it has been found that in the out-of-equilibrium state the amplitude of the oscillation of the protein's dipole moment greatly increases, thereby enhancing a possible absorption or emission of e.m. radiation. The analysis of BSA's dynamics outlined in the present paper provides a procedure for checking the propensity of a biomolecule to interact via e.m. radiation with its biochemical partners.

Published by the American Physical Society
2024
Microscopic Origin of the Entropy of Astrophysical Black Holes
Authors: Balasubramanian Vijay , Lawrence Albion , Magán Javier M. , Sasieta Martin
Published: April 2024

We construct an infinite family of microstates for black holes in Minkowski spacetime which have effective semiclassical descriptions in terms of collapsing dust shells in the black hole interior. Quantum mechanical wormholes cause these states to have exponentially small, but universal, overlaps. We show that these overlaps imply that the microstates span a Hilbert space of log dimension equal to the event horizon area divided by four times the Newton constant, explaining the statistical origin of the Bekenstein-Hawking entropy.

Published by the American Physical Society
2024
All Two-Loop Feynman Integrals for Five-Point One-Mass Scattering
Authors: Abreu Samuel , Chicherin Dmitry , Ita Harald , Page Ben , Sotnikov Vasily , Tschernow Wladimir , Zoia Simone
Published: April 2024

We compute the complete set of two-loop master integrals for the scattering of four massless particles and a massive one. Our results are ready for phenomenological applications, removing a major obstacle to the computation of complete next-to-next-to-leading order QCD corrections to processes such as the production of a H/Z/W boson in association with two jets at the LHC. Furthermore, they open the door to new investigations into the structure of quantum-field theories and provide precious analytic data for studying the mathematical properties of Feynman integrals.

Published by the American Physical Society
2024
Combined experimental and theoretical studies on glasslike transitions in the frustrated molecular conductors
θ−(BEDT−TTF)2MM′(SCN)4
Authors: Saito Yohei , Ganter Owen , Shang Chao , Hashimoto Kenichiro , Sasaki Takahiko , Winter Stephen M. , Müller Jens , Lang Michael
Published: April 2024

We present results of the coefficient of thermal expansion for the frustrated quasi-two-dimensional molecular conductor θ−(BEDT−TTF)2RbZn(SCN)4 for temperatures 1.5≤T≤290 K. A pronounced first-order phase transition anomaly is observed at the combined charge-order/structural transition at 215 K. Furthermore, clear evidence is found for two separate glasslike transitions at Tg=90–100 K and Tg†=120–130 K, similar to previous findings for θ−(BEDT−TTF)2CsZn(SCN)4 and θ−(BEDT−TTF)2CsCo(SCN)4 reported by Thomas [], both of which lack the charge-order/structural transition. Our findings indicate that these glasslike transitions are common features for the θ−(BEDT−TTF)2MM′(SCN)4 family, with M=(Rb, Cs) and M′=(Co, Zn), irrespective of the presence or absence of charge order. These results are consistent with our model calculations on the glasslike dynamics associated with the flexible ethylene end groups of the BEDT-TTF molecules for various θ−(BEDT−TTF)2MM′(SCN)4 salts, predicting two different conformational glass transitions. Moreover, calculations of the hopping integrals show a substantial degree of dependence on the end groups' conformation, suggesting a significant coupling to the electronic degrees of freedom. Our findings support the possibility that the glassy freezing of the ethylene end groups could drive or enhance glassy charge dynamics.

Published by the American Physical Society
2024
Holographic-(V)AE: An end-to-end SO(3)-equivariant (variational) autoencoder in Fourier space
Authors: Visani Gian Marco , Pun Michael N. , Angaji Arman , Nourmohammad Armita
Published: April 2024

Group-equivariant neural networks have emerged as an efficient approach to model complex data, using generalized convolutions that respect the relevant symmetries of a system. These techniques have made advances in both the supervised learning tasks for classification and regression, and the unsupervised tasks to generate new data. However, little work has been done in leveraging the symmetry-aware expressive representations that could be extracted from these approaches. Here, we present -(variational) autoencoder [H-(V)AE], a fully end-to-end SO(3)-equivariant (variational) autoencoder in Fourier space, suitable for unsupervised learning and generation of data distributed around a specified origin in 3D. H-(V)AE is trained to reconstruct the spherical Fourier encoding of data, learning in the process a low-dimensional representation of the data (i.e., a latent space) with a maximally informative rotationally invariant embedding alongside an equivariant frame describing the orientation of the data. We extensively test the performance of H-(V)AE on diverse datasets. We show that the learned latent space efficiently encodes the categorical features of spherical images. Moreover, the low-dimensional representations learned by H-VAE can be used for downstream data-scarce tasks. Specifically, we show that H-(V)AE's latent space can be used to extract compact embeddings for protein structure microenvironments, and when paired with a random forest regressor, it enables state-of-the-art predictions of protein-ligand binding affinity.

Published by the American Physical Society
2024
The integrated role of adaptive leadership, sense of empathy and communication transparency: trust building in corporate communication during the pandemic
Authors: Meng Juan , Pan Po-Lin , Cacciatore Michael A. , Sanchez Karen Robayo
Published: March 2024

Purpose

The COVID-19 pandemic has generated a significant impact on several aspects of public relations practice. By adopting the theoretical framework of adaptive leadership, this research is designed to explore how an organization’s top leadership can support related adaptive action in strategic communication. Particularly, we hope to explore whether the application of adaptive leadership could facilitate a higher level of communication transparency as well as deliver a sense of caring and empathy in COVID-19 communication.

Design/methodology/approach

An international online survey was designed and conducted for this study. The first sample consists of 776 full-time communication professionals in the United States of America with 435 women (56.1%) and 341 men (43.9%). The second sample consists of 268 full-time communication professionals in Canada, with 110 women (41.0%) and 158 men (59.0%). The two samples were merged into the final sample of 1,044 for the data analysis.

Findings

Results confirmed that the perceived impact of the COVID-19 pandemic increased communication professionals’ challenges in building trust. It also drives adaptive changes in their coping actions in strategic communication. More importantly, the top leadership within the organization played a key role in this adaptive leadership environment by demonstrating commitment to transparency in COVID-19 communication and delivering a sense of empathy during the pandemic.

Originality/value

This study contributes to our understanding of strategic communication in times of crisis, such as the COVID-19 global pandemic, by focusing on the adaptive nature of communication leadership. More importantly, our study confirms the important roles of two leadership attributes (i.e. the sense of empathy and the commitment to communication transparency) in supporting adaptive leadership, which eventually influences trust building.
The influence of ITSF on vibration of high voltage Line-Start permanent magnet synchronous motor
Authors: Yang Guanglu , Chen Si , Qiao Jianwei , Liu Yubao , Tian Fuwen , Yang Cunxiang
Published: April 2024

Purpose

The purpose of this paper is to present the influence of inter-turn short circuit faults (ITSF) on electromagnetic vibration in high-voltage line-starting permanent magnet synchronous motor (HVLSPMSMS).

Design/methodology/approach

In this paper, the ampere–conductor wave model of HVLSPMSM after ITSF is established. Second, a mathematical model of the magnetic field after ITSF is established, and the influence law of the ITSF on the air-gap magnetic field is analyzed. Further, the mathematical expression of the electromagnetic force density is established based on the Maxwell tensor method. The impact of HVLSPMSM torque ripple frequency, radial electromagnetic force spatial–temporal distribution and rotor unbalanced magnetic tension force by ITSF is revealed. Finally, the electromagnetic–mechanical coupling model of HVLSPMSM is established, and the vibration spectra of the motor with different degrees of ITSF are solved by numerical calculation.

Findings

In this study, it is found that the 2np order flux density harmonics and (2 N + 1) p order electromagnetic forces are not generated when ITSF occurs in HVLSPMSM.

Originality/value

By analyzing the multi-harmonics of HVLSPMSM after ITSF, this paper provides a reliable method for troubleshooting from the perspective of vibration and torque fluctuation and rotor unbalanced electromagnetic force.
Workspace in supporting strategy implementation – a study of 25 knowledge-intensive organisations
Authors: Wäistö Pia , Ukko Juhani , Rantala Tero
Published: April 2024

Purpose

Organisational strategy becomes reality by connecting organisation’s resources and capabilities in daily operations, and physical workspace is one of the environments in which this takes place. This study aims to explore to what extent factors required for successful strategy implementation are considered when designing, using and managing workspaces of knowledge-intensive organisations.

Design/methodology/approach

For the study, managers in 25 large and medium-sized knowledge-intensive organisations were interviewed. The semi-structured interviews focused on organisation’s strategy, strategy implementation practices and workspace design and management. To form a comprehensive framework of strategy implementation success factors for the study, the factors of 11 frameworks were analysed, grouped and renamed.

Findings

Current workspace design, usage and management mainly support human-related strategy implementation factors. However, both organisation- and human-related factors are needed for the strategy implementation to be successful. Therefore, the organisations studied may have unused potential in their workspaces to ensure strategy-aligned operations and behaviour.

Practical implications

Due to the potential imbalance between organisation- and human-related strategy implementation factors, a more holistic, organisational-level approach to workspace design, usage and management is recommended to ensure the success of strategy implementation.

Originality/value

Workspaces have extensively been studied from individual strategy implementation factors’ as well as employees’ perspectives. Prior to this work, there are only few studies exploring workspace in the holistic, strategy implementation context.
Thermal-hydraulic performance of turbulent flows across a heated round tube installed through several perforated twisted tapes
Authors: Perng Shiang-Wuu , Wu Horng Wen , Huang De-An
Published: April 2024

Purpose

The purpose of this study is to advance turbulent thermal convection inside the constant heat-flux round tube inserted by multiple perforated twisted tapes.

Design/methodology/approach

The novel design of this study is accomplished by inserting several twisted tapes and drilling some circular perforations near the tape edge (C1, C3, C5: solid tapes; C2, C4, C6: perforated tapes). The turbulence flow appearances and thermal convective features are examined for various Reynolds numbers (8,000–14,000) using the renormalization group (RNG)

κ−ε turbulent model and Semi-Implicit Method for Pressure-Linked Equations (SIMPLE) algorithm.

Findings

The simulated outcomes reveal that inserting more perforated-twisted tapes into the heated round tube promotes turbulent thermal convection effectively. A swirling flow caused by the twisted tapes to produce the secondary flow jets between two reverse-spin tapes can combine with the main flow passing through the perforations at the outer edge to enhance the vortex flow. The primary factors are the quantity of twisted tapes and with/without perforations, as the perforation ratio remains at 2.5 in this numerical work. Weighing friction along the tube, C6 (four reverse-spin perforated-twisted tapes) brings the uppermost thermal-hydraulic performance of 1.23 under Re = 8,000.

Research limitations/implications

The constant thermo-hydraulic attributes of liquid water and the steady Newtonian fluid are research limitations for this simulated work.

Practical implications

The simulated outcomes will avail the inner-pipe design of a heat exchanger inserted by multiple perforated twisted tapes to enhance superior heat transfer.

Originality/value

These twisted tapes form tiny circular perforations along the tape edge to introduce the fluid flow through these bores and combine with the secondary flow induced between two reverse-spin tapes. This scheme enhances the swirling flow, turbulence intensity and fluid mixing to advance thermal convection since larger perforations cannot produce large jet velocity or the position of perforations is too far from the tape edge to generate a separated flow. Consequently, this work contributes a valuable cooling mechanism toward thermal engineering.
Evaluation of high quality and full employment based on CRITIC-entropy-TOPSIS multi-criteria framework
Authors: Wei Minyan , Zheng Juntao , Zeng Shouzhen , Jin Yun
Published: April 2024

Purpose

The main aim of this paper is to establish a reasonable and scientific evaluation index system to assess the high quality and full employment (HQaFE).

Design/methodology/approach

This paper uses a novel Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) multi-criteria framework to evaluate the quality and quantity of employment, wherein the integrated weights of attributes are determined by the combined the Criteria Importance Through Inter-criteria Correlation (CRITIC) and entropy approaches.

Findings

Firstly, the gap in the Yangtze River Delta in employment quality is narrowing year by year; secondly, employment skills as well as employment supply and demand are the primary indicators that determine the HQaFE; finally, the evaluation scores are clearly hierarchical, in the order of Shanghai, Jiangsu, Zhejiang and Anhui.

Originality/value

A scientific and reasonable evaluation index system is constructed. A novel CRITIC-entropy-TOPSIS evaluation is proposed to make the results more objective. Some policy recommendations that can promote the achievement of HQaFE are proposed.