bluuebunny/crossref_metadata_2025 huggingface dataset:
A-site cation engineering of cesium and MAPb0.5Sn0.5I3 perovskite: the properties and optoelectronic performance analysis using DFT calculations
Authors: Mbumba Manala Tabu , Mahona John , Kihedu Joseph , Chang’waro Salum K. , John Geoffrey R.
Published: November 2023

Here, the first-principle calculations with the density functional theory calculations with PBE exchange–correlation functional were employed in investigating the effect of Cesium in the properties and optoelectronic performance of MAPb0.5Sn0.5I3 perovskite using A-site cation engineering technique. The control and Cesium based perovskites were generated and computed through CASTEP analysis from Material studio to determine their properties as well as optoelectronic performance. The findings revealed an improved properties of Cesium added perovskite compared to control ones. However, above 15%Cesium, phase separation was seen which declined the quality of the perovskite films. Moreover, simulation results of perovskites added with Cesium to 15% have demonstrated to have an improved optoelectronic performance as well as thermal stability by maintaining about 76% compared to the control which can retain about 39% of their initial power conversion efficiency after 15 days of aging at 85 °C in the ambient condition. This research presents a viable approach to investigate the impact of cation composition tuning on band gap, which can be extended to other perovskites. Additionally, it offers a broad set of design guidelines prior experiments for attaining a targeted band gap and modifying perovskite crystallization to enhance the characteristics, thermal stability, and optoelectronic performance of perovskite solar cells.
The UNGPs and ISDS: Should Businesses Assess the Human Rights Impacts of Investor–State Arbitration?
Authors: Triefus Stephanie
Published: November 2023

Investor–state dispute settlement (ISDS) has been heavily criticized from the perspective of human rights. However, the potential adverse human rights impacts of ISDS and the responsibilities of businesses to avoid causing or contributing to those impacts under the UN Guiding Principles on Business and Human Rights have yet to be spelled out. Although states are currently reforming ISDS, progress has been slow, and businesses have an independent responsibility to ensure that their operations do not harm human rights. Against this background, this article unpacks how businesses might contribute to three non-exhaustive examples of potential human rights impacts of ISDS: namely, the chilling effect on human rights regulation, crippling mega-awards and direct impacts on third-party rights. This article breaks new ground by exploring how human rights due diligence could be a useful tool for businesses to identify and address these impacts.
Honorific mismatches of coordinate subjects in Korean
Authors: Kim Jeong-Seok , Jung Duk-Ho , Lee Jin Hyung
Published: November 2023

In this article, we explore whether hierarchy and linearity conspire to affect agreement. The data come from an experimental study of honorific agreement between verbal si and coordinate subjects in Korean. We focus on computing the mismatch driven by honorifically mixed conjuncts. Unlike South Slavic gender agreement, Korean has neither Resolved Agreement nor First Conjunct Agreement. Only Last Conjunct Agreement is attested in Korean honorification. We show that honorific agreement within coordinate subjects is triggered only when the honorific verbal si appears, which is substantially different from the case with the honorific nominal nim. We also show that acceptability significantly decreases when the last conjunct of coordinate subjects is incongruous with an honorific verb. We thus argue that verbal honorific agreement with Korean coordinate subjects is sensitive to linear order, mimicking South Slavic gender agreement.
Echo Chambers and Friendship
Authors: Güngör Alper
Published: November 2023

Are the members of echo chambers blameworthy for their beliefs? If we follow Sarah Stroud's account of friendship, we end up with the following conclusion: if echo chambers involve friendship, then the individuals have strong reasons not to live up to epistemic demands or ideals when the friendships are formed in the echo chambers they are members of. This result stands in striking contrast with the received view, according to which the members of echo chambers are blameworthy for their epistemic vices and faulty beliefs. The received view uses individual epistemic vices to propose individualistic solutions for the problem of echo chambers. I argue that this is misleading, simply because the members of echo chambers are not blameworthy due to the friendships cultivated in the echo chambers.
On the nilpotent orbit theorem of complex variations of Hodge structure
Authors: Deng Ya
Published: November 2023

We prove some results on the nilpotent orbit theorem for complex variations of Hodge structure.
Impact of historic sediment characterisation on predicting polychaete distributions: a case study of so-called muddy habitat shovelhead worms (Annelida: Magelonidae)
Authors: Mills Kimberley , Mortimer Kate
Published: November 2023

Shovelhead worms are common polychaetes around the British Isles and have been recorded in numerous ecological surveys. Yet, understanding of their habitat conditions is poor, based heavily on visual observations of sediments from historical records. In this study, the drivers of abundance and geographical distribution of two morphologically and behaviourally diverse species Magelona alleni and Magelona minuta are investigated by reanalysing sediment characteristics and depths from museum marine monitoring surveys. Although both species are historically associated with muddy sediments, the records herein suggest that M. alleni occurs in an extensive range of sediments, but is more abundant at localities with more than 25% sand. In comparison, M. minuta shows a negative linear relationship between grain diameter and abundance, corroborating previous work that the species is abundant in fine-grained mud. The depth records show that while M. alleni predominates below 60 m, M. minuta is a distinct offshore species. These differences may be attributed to the interspecific variation in morphology and motility between the species: M. alleni is stout and tube-dwelling, while M. minuta is fragile, small, and fairly motile. To corroborate these findings, sediment grains from tubes of M. alleni were classified using the Udden–Wentworth grain size scale and suggest sand is the key component for tube construction. Overall, this study highlights that sediment parameters for M. alleni have been misinterpreted and generalised in historical records, emphasising the importance of quantitative sediment analysis in defining the habitat of Magelona.
Songs materialising as music: medieval monophony in song books and music manuscripts
Authors: HUCK OLIVER
Published: November 2023

This survey of the mise-en-page of manuscripts that include medieval monophonic song focuses on complex multigraphic written artefacts presenting music on staves. Comparing the formatting of thirteenth-century French chansonniers and fifteenth-century collections of monophonic songs (BnF fr. 9346 and BnF fr. 12744), there are obvious differences in the mise-en-page. But when, where and why did the changes in the production of manuscripts and the materialisation of songs take place? This article proposes a distinction between entirely pre-ruled ‘“full” music manuscripts’, ‘music manuscripts’ employing pre-ruling and ‘manuscripts with music’ where the staves were drawn only after the text has been written. Moreover, ‘songbooks’ mainly interested in lyrics can be distinguished from ‘song books’ focusing on the music. The interrelation of production process, content and manuscript type is discussed using the example of the conductus In hoc ortus occidente. The emergence, interrelation and particularities of layouts are discussed for vernacular thirteenth- or fourteenth-century songbooks with Dutch, English/Anglo-Norman, French, Galego-Portuguese, German, Italian and Occitan texts. The two-column layout is found in songbooks all over Europe (except for Italian laudari). This article examines models such as rolls, libelli, Dominican liturgical books, particularities of layouts such as different strophic page layouts and as the separation of verses in some troubadour chansonniers and Galego-Portuguese cancionieros as well as the dissemination in German speaking regions through minstrel schools. Comparing French, German and Italian song books of monophonic song as well lais/Leich and/or polyphony reveals differences in the production process of Italian ‘“full” music manuscripts’ (BAV Rossi 215/I-OST, I-REas and I-Fl Mediceo Palatino 87), German ‘music manuscripts’ (A-Wn 2701, A-Wn 2777 and CZ-Pu XI E 9) and French ‘manuscripts with music’ (BnF fr. 146 and the Machaut-collections).
The responsories of the Old Hispanic Night Office and their sources
Authors: RANDEL DON MICHAEL
Published: November 2023

Despite their paucity, the surviving sources for the Old Hispanic Rite make possible the identification of the earliest kernel of responsories for the Night Office. They show how this first group of responsories, assigned to the Ferial Office, was subsequently distributed over the Sundays of Lent. Comparison of the notation for these responsories, both refrains and verses, across the several sources enables a more solid geographical grouping of the manuscripts than do the palaeographical studies of the verbal texts that have hitherto prevailed.
Development and Validation of a New Tool to Improve the Accuracy of the Hospital Mass-Casualty Incident Response Plan Activation: The PEMAAF Score
Authors: Ruffini Claudia , Trentin Monica , Corona Alberto , Caviglia Marta , Sechi Giuseppe Maria , Migliari Maurizio , Stucchi Riccardo , Ragazzoni Luca , Fumagalli Roberto
Published: November 2023

Introduction:

Effective response to a mass-casualty incident (MCI) entails the activation of hospital MCI plans. Unfortunately, there are no tools available in the literature to support hospital responders in predicting the proper level of MCI plan activation. This manuscript describes the scientific-based approach used to develop, test, and validate the PEMAAF score (Proximity, Event, Multitude, Overcrowding, Temporary Ward Reduction Capacity, Time Shift Slot [Prossimità, Evento, Moltitudine, Affollamento, Accorpamento, Fascia Oraria], a tool able to predict the required level of hospital MCI plan activation and to facilitate a coordinated activation of a multi-hospital network.

Methods:

Three study phases were performed within the Metropolitan City of Milan, Italy: (1) retrospective analysis of past MCI after action reports (AARs); (2) PEMAAF score development; and (3) PEMAAF score validation. The validation phase entailed a multi-step process including two retrospective analyses of past MCIs using the score, a focus group discussion (FGD), and a prospective simulation-based study. Sensitivity and specificity of the score were analyzed using a regression model, Spearman’s Rho test, and receiver operating characteristic/ROC analysis curves.

Results:

Results of the retrospective analysis and FGD were used to refine the PEMAAF score, which included six items–Proximity, Event, Multitude, Emergency Department (ED) Overcrowding, Temporary Ward Reduction Capacity, and Time Shift Slot–allowing for the identification of three priority levels (score of 5-6: green alert; score of 7-9: yellow alert; and score of 10-12: red alert). When prospectively analyzed, the PEMAAF score determined most frequent hospital MCI plan activation (>10) during night and holiday shifts, with a score of 11 being associated with a higher sensitivity system and a score of 12 with higher specificity.

Conclusions:

The PEMAAF score allowed for a balanced and adequately distributed response in case of MCI, prompting hospital MCI plan activation according to real needs, taking into consideration the whole hospital response network.
Wenn es zu bunt wird, gehe ich wieder
Authors: Rüegg Sebastian
Published: November 2023

Was ist zu diesem Thema bereits bekannt?

Im Gegensatz zu der von Patient_innen ausgehenden Aggression und Gewalt gegenüber Fachpersonen, stellen die Gewaltanteile psychiatrischer Pflege ein Tabuthema dar.

Wie wird eine neue Perspektive eingebracht?

Im Artikel wird die Thematik mit Fokus auf die Sichtweise von Berufseinsteiger_innen und Studierenden aus dem letzten Ausbildungsjahr dargestellt.

Was sind die Auswirkungen für die Praxis?

Gewaltanteile Psychiatrischer Pflege können für Berufseinsteiger_innen und Studierende eine berufliche Sozialisation Widerwillen und eine hohe Unzufriedenheit mit der Berufsausübung mit sich bringen. Fehlende Reflexionsmöglichkeiten und die Tabuisierung der verschiedenen Gewaltanteile verstärken die Problematik zusätzlich.
Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis
Authors: Lambrecht Rebekka , Rudolf Franziska , Ückert Anna-Katharina , Sladky Valentina C. , Phan Truong San , Jansen Jasmin , Naim Samara , Kaufmann Thomas , Keogh Adrian , Kirschnek Susanne , Mangerich Aswin , Stengel Florian , Leist Marcel , Villunger Andreas , Brunner Thomas
Published: November 2023

Paracetamol (acetaminophen, APAP) overdose severely damages mitochondria and triggers several apoptotic processes in hepatocytes, but the final outcome is fulminant necrotic cell death, resulting in acute liver failure and mortality. Here, we studied this switch of cell death modes and demonstrate a non-canonical role of the apoptosis-regulating BCL-2 homolog BIM/Bcl2l11 in promoting necrosis by regulating cellular bioenergetics. BIM deficiency enhanced total ATP production and shifted the bioenergetic profile towards glycolysis, resulting in persistent protection from APAP-induced liver injury. Modulation of glucose levels and deletion of Mitofusins confirmed that severe APAP toxicity occurs only in cells dependent on oxidative phosphorylation. Glycolytic hepatocytes maintained elevated ATP levels and reduced ROS, which enabled lysosomal recycling of damaged mitochondria by mitophagy. The present study highlights how metabolism and bioenergetics affect drug-induced liver toxicity, and identifies BIM as important regulator of glycolysis, mitochondrial respiration, and oxidative stress signaling.
Genetic evidence for causal effects of leukocyte counts on risk for rheumatoid arthritis
Authors: You Jin-Mei , Zhang Yao-Chen , Fan Ke-Yi , Bai Shang-Kai , Zhang Zi-Yu , Zhang He-Yi , Cheng Ting , Huo Yue-Hong , Wang Cai-Hong , Li Xiao-Feng , Zhang Sheng-Xiao
Published: November 2023

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation of leukocytes and inflammatory mediators within the synovial tissue. Leukocyte counts are proposed to play a role in the pathogenesis of RA. However, the causality remains unclear. To investigate the causal relationship between various leukocytes and RA by implementing two-sample univariable Mendelian Randomization (MR) and multivariable MR. MR analysis was performed using respective genome-wide association study (GWAS) summary statistics for the exposure traits (eosinophil counts, neutrophil counts, lymphocyte counts, monocyte counts, basophil counts, and white blood cell counts) and outcome trait (RA). Summary statistics for leukocytes were extracted from the Blood Cell Consortium meta-analysis and INTERVAL studies. Public GWAS information for RA included 14,361 cases and 43,923 controls. Inverse variance weighted, weighted median, MR-Egger regression, MR pleiotropy residual sum and outlier, and multivariable MR analyses were performed in MR analysis. Univariable MR found elevated eosinophil counts (OR 1.580, 95% CI 1.389–2.681, p = 1.30 × 10–7) significantly increased the risk of RA. Multivariable MR further confirmed that eosinophil counts were a risk factor for RA. Increased eosinophils were associated with higher risk of RA. Further elucidations of the causality and mechanisms underlying are likely to identify feasible interventions to promote RA prevention.
A population-based study on incidence trends of myeloma in the United States over 2000–2020
Authors: Mousavi Seyed Ehsan , Ilaghi Mehran , Aslani Armin , Yekta Zahra , Nejadghaderi Seyed Aria
Published: November 2023

Myeloma is one of the most common types of haematological malignancies. We aimed to investigate the incidence rates of myeloma by sex, race, age, and histological subgroups in the United States (US) over 2000–2020. Data were retrieved from the the Surveillance, Epidemiology, and End Results (SEER) 22 database. The International Classification of Diseases for Oncology version 3 morphological codes 9731, 9732, and 9734 were assigned for solitary plasmacytoma of bone, plasma cell myeloma, and extraosseous plasmacytoma, respectively. Average annual percent change (AAPC) and the pairwise comparison with the parallelism and coincidence were reported. All estimates were reported as counts and age-adjusted incidence rates per 100,000 individuals. Over 2000–2019, most of myeloma cases were among those aged at least 55 years (85.51%), men (54.82%), and non-Hispanic Whites (66.67%). Among different subtypes, plasma cell myeloma with 193,530 cases had the highest frequency over the same period. Also, there was a significant decrease in the age-standardized incidence rate of myeloma across all races/ethnicities in both sexes within all age groups (AAPC: − 8.02; 95% confidence interval (CI): − 10.43 to − 5.61) and those aged < 55 (AAPC: − 8.64; 95% CI − 11.02 to − 6.25) from 2019 to November 2020. The overall trends of myeloma incidence rates were not parallel, nor identical. There was an increase in myeloma incidence in both sexes, with a highly increasing rate, particularly among younger Hispanic and non-Hispanic Black women over 2000–2019. However, a remarkable decline was observed in the incidence rates following the COVID-19 pandemic in 2020.
A nicking enzyme-assisted allosteric strategy for self-resetting DNA switching circuits
Authors: Wang Haoliang , Zhang Xiaokang , Liu Yuan , Zhou Shihua
Published: November 2023

The self-regulation of biochemical reaction networks is crucial for maintaining balance, stability, and adaptability within biological systems.
Critical role of hydrogen bonding between microcrystalline cellulose and g-C3N4 enables highly efficient photocatalysis
Authors: Wang Zhaoqiang , Ding Guixiang , Zhang Juntao , Lv Xianqing , Wang Peng , Shuai Li , Li Chunxue , Ni Yonghao , Liao Guangfu
Published: November 2023

Hydrogen bonding between CN and MCC enables excellent charge separation and migration, leading to the outstanding photoelectrochemical properties of MCC/CN.
Formation of superoxide and ozone-like species on Cu doped CeO2(111) and their CO oxidation reactivity: a DFT study
Authors: Wang Hao , Li Yuan , Han Jiao , Zhang Caishun , Wang Honghao , Liu Daosheng , Hou Xiaoning , Zhang Lei , Gao Zhixian
Published: November 2023

Besides O2δ−, O3δ− formed upon O2 adsorption on oxygen vacancies of Cu/CeO2(111). CO interacted with either O2δ− or O3δ− to form CO2 or carbonates energetically compared with lattice [O], and a modified M–vK mechanism for CO oxidation was suggested.
Recent advances in point-of-care testing of COVID-19
Authors: Lee Sungwoon , Bi Liyan , Chen Hao , Lin Dong , Mei Rongchao , Wu Yixuan , Chen Lingxin , Joo Sang-Woo , Choo Jaebum
Published: November 2023

This review explores various point-of-care optical diagnostic systems combined with microdevices developed during the recent COVID-19 pandemic for clinical diagnostics.
A highly efficient lanthanide coordination polymer luminescent material for the multi-task detection of environmental pollutants
Authors: Wang Xin , He Shunsheng , Chen Jun , Wei Jiamin , Chen Chaoyue , Shi Wenyan , Wu Dayu , Fu Lianshe , Yang Tinghai
Published: November 2023

A novel terbium coordination polymer based on pyrazole carboxylic acid was designed and synthesized. Its applications as a luminescent chemosensor toward Fe3+, Cr2O72− and 2,4,6-trinitrophenol have been explored in detail.
Synthesis and catalytic activity of tetradentate β-diketiminato rare-earth metal monoalkyl complexes in tandem Oppenauer oxidation and cross-aldol condensation
Authors: Zou Haiyan , Wang Ziqian , Guo Dianjun , Zhang Lijun , Wang Shaowu , Zhu Xiancui
Published: November 2023

Tetradentate β-diketiminato rare-earth complexes initiated the Oppenauer oxidation and cross-aldol condensation of alcohols, affording various ketones and α-mono-substituted and α,α′-bis-substituted benzylidene alkanones under mild conditions.
Selective synthesis of functionalized linear aliphatic primary amines via decarboxylative radical-polar crossover
Authors: Cauwenbergh Robin , Sahoo Prakash Kumar , Maiti Rakesh , Mathew Abra , Kuniyil Rositha , Das Shoubhik
Published: November 2023

Organic photoredox-driven generation of distant primary radicals for the hydroaminoalkylation of styrenes or Michael acceptors, yielding linear aliphatic primary amines, including late-stage functionalisation and total synthesis of drug compounds.
An automated carcinogenic potency categorization approach for nitrosamine drug substance-related impurities
Authors: Zhu Jiazhou , Qu Yang , Ye Ning
Published: November 2023

A web-based application that can autonomously analyze the risk category of N-nitrosamine compounds from their SMILES notation, providing instant screening to identify high-risk formations of N-nitrosamines.
A self-assembled nanoprobe based on Schiff base for the rapid and selective detection of serum albumin with cell imaging applications
Authors: Moni Dolan , Sasmal Mihir , Islam Abu Saleh Musha , Dutta Ananya , Maiti Debjani , Khatun Rousunara , Katarkar Atul , Ali Mahammad
Published: November 2023

A Schiff base based probe, DBNHC was found to undergo self aggregation in PBS buffer resulting very weakly fluorescence, but in the presence of BSA it becomes highly fluorescent due to disassembly of nanoaggregates into monomer and trapping at site II in BSA.
Influence of Breed and Body Conformation on Vertebral Implant Insert Angles in Dogs
Authors: Nowak Lina , Grapes N. , De Decker S.
Published: November 2023

Objective To evaluate the effect of breed and body conformation on the vertebral insertion corridor angles for stabilizing spinal surgery in dogs.

Study Design Computed tomography studies of the vertebral column of 100 dogs from 10 representatives of 10 FCI (Fédération Cynologique Internationale) breed groups were randomly and blindly evaluated for vertebral insertion corridor angles. Insertion angles were measured for the last six cervical vertebrae (C2–C7), the last four thoracic vertebrae (T10–T13), the seven lumbar vertebrae (L1–L7), and the sacrum (S1).

Results Insertion angle was significantly influenced by breed at C6 (p = 0.001), C7 (p = 0.008), T13 (p = 0.032), L6 (p = 0.011), and S1 (p = 0.009). At C6, Pugs had significantly larger mean insertion angles (MIAs) compared with Beagles (p = 0.016), Miniature Dachshunds (p = 0.024), Greyhounds (p = 0.004), and West Highland White Terriers (p = 0.001). English Springer Spaniels had significantly smaller MIA at C7 compared with Siberian Huskies (p = 0.037) and Pugs (p = 0.033). German Shepherds had significantly smaller MIA at L6 compared with Beagles (p = 0.044), Miniature Schnauzers (p = 0.029), and English Springer Spaniels (p = 0.047). Miniature Dachshunds had significantly larger MIA at S1 compared with Beagles (p = 0.009), Pugs (p = 0.015), Miniature Schnauzers (p = 0.010), and English Springer Spaniels (p = 0.006).

Conclusion Breed and body conformation are important factors when planning instrumented spinal surgery in dogs. Individualized planning for spinal instrumentation seems to be critical.
Lymphatic venous anastomosis and complex decongestive therapy for lymphoedema: randomized clinical trial
Authors: Mihara Makoto , Hara Hisako , Kawasaki Yohei , Mitsuhashi Toshiharu , Orikasa Hideki , Ando Hirohiko , Naito Munekazu
Published: November 2023

Background

Lymphatic venous anastomosis is associated with a low incidence of lower extremity lymphoedema-associated cellulitis; however, the exact relationship is unknown. This multicentre RCT evaluated the effect of lymphatic venous anastomosis on prevention of cellulitis.

Methods

Patients with secondary lower extremity lymphoedema who underwent at least 3 months of non-operative decongestive therapy were assigned randomly to lymphatic venous anastomosis or conservative therapy. The primary and secondary outcomes were cellulitis frequency, and assessments of circumference, hardness, and pain respectively.

Results

Overall, 336 patients were divided into two groups: 225 in the full-analysis set (primary outcome 225; secondary outcomes 170) and 156 in the per-protocol set (primary outcome 156; secondary outcomes 110). In both analyses, lymphatic venous anastomosis with non-operative decongestive therapy was more effective in preventing cellulitis than non-operative decongestive therapy alone; the difference between groups in reducing cellulitis frequency over 6 months was −0.35 (95 per cent c.i. −0.62 to −0.09; P = 0.010) in the full-analysis set (FAS) and −0.60 (−0.94 to −0.27; P = 0.001) in the per-protocol set (PPS) Limb circumference and pain were not significantly different, but lymphatic venous anastomosis reduced thigh area hardness (proximal medial and distal and lateral proximal). Four patients experienced contact dermatitis with non-operative decongestive therapy alone.

Conclusion

Lymphatic venous anastomosis in combination with non-operative decongestive therapy prevents cellulitis.

Registration number

UMIN00025137, UMIN00031462.
Differential involvement of mitochondria in post-tetanic potentiation at intracortical excitatory synapses of the medial prefrontal cortex
Authors: Lee Hyoung-Ro , Choi Sung Hoon , Lee Suk-Ho
Published: November 2023

Post-tetanic Ca2+ release from mitochondria produces presynaptic residual calcium, which contributes to post-tetanic potentiation. The loss of mitochondria-dependent post-tetanic potentiation is one of the earliest signs of Alzheimer’s model mice. Post-tetanic potentiation at intracortical synapses of medial prefrontal cortex has been implicated in working memory. Although mitochondrial contribution to post-tetanic potentiation differs depending on synapse types, it is unknown which synapse types express mitochondria-dependent post-tetanic potentiation in the medial prefrontal cortex. We studied expression of mitochondria-dependent post-tetanic potentiation at different intracortical synapses of the rat medial prefrontal cortex. Post-tetanic potentiation occurred only at intracortical synapses onto layer 5 corticopontine cells from commissural cells and L2/3 pyramidal neurons. Among post-tetanic potentiation-expressing synapses, L2/3-corticopontine synapses in the prelimbic cortex were unique in that post-tetanic potentiation depends on mitochondria because post-tetanic potentiation at corresponding synapse types in other cortical areas was independent of mitochondria. Supporting mitochondria-dependent post-tetanic potentiation at L2/3-to-corticopontine synapses, mitochondria-dependent residual calcium at the axon terminals of L2/3 pyramidal neurons was significantly larger than that at commissural and corticopontine cells. Moreover, post-tetanic potentiation at L2/3-corticopontine synapses, but not at commissural-corticopontine synapses, was impaired in the young adult Alzheimer’s model mice. These results would provide a knowledge base for comprehending synaptic mechanisms that underlies the initial clinical signs of neurodegenerative disorders.
Detecting a disc bending wave in a barred-spiral galaxy at redshift 4.4
Authors: Tsukui Takafumi , Wisnioski Emily , Bland-Hawthorn Joss , Mai Yifan , Iguchi Satoru , Baba Junichi , Freeman Ken
Published: November 2023

The recent discovery of barred spiral galaxies in the early Universe (z > 2) poses questions of how these structures form and how they influence galaxy evolution in the early Universe. In this study, we investigate the morphology and kinematics of the far-infrared (FIR) continuum and [C ii] emission in BRI1335-0417 at z ≈ 4.4 from ALMA observations. The variations in position angle and ellipticity of the isophotes show the characteristic signature of a barred galaxy. The bar, $3.3^{+0.2}_{-0.2}$ kpc long in radius and bridging the previously identified two-armed spiral, is evident in both [C ii] and FIR images, driving the galaxy’s rapid evolution by channelling gas towards the nucleus. Fourier analysis of the [C ii] velocity field reveals an unambiguous kinematic m = 2 mode with a line-of-sight velocity amplitude of up to ∼30–40 km s−1; a plausible explanation is the disc’s vertical bending mode triggered by external perturbation, which presumably induced the high star formation rate and the bar/spiral structure. The bar identified in [C ii] and FIR images of the gas-rich disc galaxy (≳ 70 per cent of the total mass within radius R ≈ 2.2 disc scale lengths) suggests a new perspective of early bar formation in high redshift gas-rich galaxies – a gravitationally unstable gas-rich disc creating a star-forming gaseous bar, rather than a stellar bar emerging from a pre-existing stellar disc. This may explain the prevalent bar-like structures seen in FIR images of high-redshift submillimeter galaxies.
Probing cosmic isotropy in the Local Universe
Authors: Franco Camila , Avila Felipe , Bernui Armando
Published: November 2023

This is a model-independent analysis that investigates the statistical isotropy in the Local Universe using the Arecibo Legacy Fast ALFA (ALFALFA) survey data (0 < z < 0.06). We investigate the angular distribution of H i extragalactic sources from the ALFALFA catalogue and study whether they are compatible with the statistical isotropy hypothesis using the two-point angular correlation function (2PACF). Aware that the Local Universe is plenty of clustered structures and large voids, we compute the 2PACF with the Landy–Szalay estimator performing directional analyses to inspect 10 sky regions. We investigate these 2PACF using power-law best-fitting analyses, and determine the statistical significance of the best-fitting parameters for the 10 ALFALFA regions by comparison with the ones obtained through the same procedure applied to a set of mock catalogues produced under the homogeneity and isotropy hypotheses. Our conclusion is that the Local Universe, as mapped by the H i sources of the ALFALFA survey, is in agreement with the hypothesis of statistical isotropy within $2\sigma$ confidence level, for small- and large-angle analyses, with the only exception of one region – located near the Dipole Repeller – that appears slightly outlier ($2.4\sigma$). Interestingly, regarding the large angular distribution of the H i sources, we found three regions where the presence of cosmic voids reported in the literature left their signature in our 2PACF, suggesting projected large underdensities there, with number-density contrast δ ≃ −0.7. According to the current literature, these regions correspond, partially, to the sky position of the void structures known as Local Cosmic Void and Dipole Repeller.
Machine-learning enhanced photometric analysis of the extremely bright GRB 210822A
Authors: Angulo-Valdez Camila , Becerra Rosa L , Pereyra Margarita , Garcia-Cifuentes Keneth , Vargas Felipe , Watson Alan M , De Colle Fabio , Fraija Nissim , Butler Nathaniel R , Dainotti Maria G , Dichiara Simone , Lee William H , Troja Eleonora , Bloom Joshua S , González J Jesús , Kutyrev Alexander S , Prochaska J Xavier , Ramirez-Ruiz Enrico , Richer Michael G
Published: November 2023

We present analytical and numerical models of the bright long GRB 210822A at z = 1.736. The intrinsic extreme brightness exhibited in the optical, which is very similar to other bright GRBs (e.g. GRBs 080319B, 130427A, 160625A 190114C, and 221009A), makes GRB 210822A an ideal case for studying the evolution of this particular kind of GRB. We use optical data from the RATIR instrument starting at T + 315.9 s, with publicly available optical data from other ground-based observatories, as well as Swift/UVOT, and X-ray data from the Swift/XRT instrument. The temporal profiles and spectral properties during the late stages align consistently with the conventional forward shock model, complemented by a reverse shock element that dominates optical emissions during the initial phases (T < 300 s). Furthermore, we observe a break at T = 80 000 s that we interpreted as evidence of a jet break, which constrains the opening angle to be about θj = (3–5) degrees. Finally, we apply a machine-learning technique to model the multiwavelength light curve of GRB 210822A using the afterglowpy library. We estimate the angle of sight θobs = (6.4 ± 0.1) × 10−1 degrees, the energy E0 = (7.9 ± 1.6) × 1053 erg, the electron index p = 2.54 ± 0.10, the thermal energy fraction in electrons ϵe = (4.63 ± 0.91) × 10−5 and in the magnetic field ϵB = (8.66 ± 1.01) × 10−6, the efficiency χ = 0.89 ± 0.01, and the density of the surrounding medium n0 = 0.85 ± 0.01 cm−3.
A new star formation recipe for magnetohydrodynamics simulations of galaxy formation
Authors: Girma Eden , Teyssier Romain
Published: November 2023

Star formation has been observed to occur at globally low yet locally varying efficiencies. As such, accurate capture of star formation in numerical simulations requires mechanisms that can replicate both its smaller scale variations and larger scale properties. Magnetic fields are thought to play an essential role within the turbulent interstellar medium (ISM) and affect molecular cloud collapse. However, it remains to be fully explored how a magnetized model of star formation might influence galaxy evolution. We present a new model for a sub-grid star formation recipe that depends on the magnetic field. We run isolated disc galaxy simulations to assess its impact on the regulation of star formation using the code ramses. Building upon existing numerical methods, our model derives the star formation efficiency from local properties of the sub-grid magnetized ISM turbulence, assuming a constant Alfvén speed at sub-parsec scales. Compared to its non-magnetized counterpart, our star formation model suppresses the initial starburst by a factor of 2 while regulating star formation later on to a nearly constant rate of ∼1 M⊙ yr−1. Differences also arise in the local Schmidt law with a shallower power-law index for the magnetized star formation model. Our results encourage further examination into the notion that magnetic fields are likely to play a non-trivial role in our understanding of star and galaxy formation.
Integrating Histology in the Medical Curriculum
Authors: Bolender David
Published: November 2023

Transition from a freestanding Cell and Tissue Biology (histology) course to participation within an integrated curriculum has its challenges. As material from a single course becomes fragmented into several academic units across different years, there is a loss in appreciation of the structural continuum from cells to tissue to organs. The change in impact from a stand‐alone course to a minor component of academic units affects the value students place on study time and perceived impact on exams. In our experience, these factors have lead to a devaluation of the importance histology plays in the medical curriculum. This is realized in reduced student attendance at scheduled labs and their preference for an abbreviated overview session over a more active learning lab experience. As a faculty, we are challenged to create a valued experience in a very crowed curriculum.
New Antibiotics For The Post‐Antibiotic Era
Authors: Mobashery Shahriar
Published: November 2023

β‐Lactam antibiotics are the most important antibiotics targetting the bacterial cell wall. However, their utility has been compormised due to broad resistance by bacteria to these antibiotics. Yet, their targets, penicillin‐binding proteins (PBPs) still remain important targets for antibiotics. The importance of PBPs, especially the high‐molcular‐mass variants, is due to their critical functions in biosynhesis of bacterial cell wall. But equally important, these proteins decorate the surface of the plasma membrane, hence access by antibiotics is often less of a problem than is for the cytoplasmic targets. I will describe an in silico search for novel classes of antibiotics carried out with the X‐ray structure of the PBP2a from methicillin‐resistant Staphylococcus aureus (MRSA). MRSA is a global scourge, infections by which afflicate 100,000 individuals annually in the USA alone. A significant proportion of these cases leads to mortality. Resistance to β‐lactam antibiotics in these organisms is overencompassing, including penicillins, cephalosporins, carbapenems, among others. I will describe discovery of the oxadiazole and quinazolinone classes of antibacterials, which target PBPs in MRSA. The lead compounds were elaborated synthetically into a library of several hundred members, which were screened for antibacterial activity. Both classes of antibiotics target bacterial cell‐wall biosynthesis, they exhibit favorable pharmacokinetic properties, they are efficacious in rodent models of MRSA infection and they are orally bioavailable. Both classes of compounds hold great promise in addressing clinical needs in treating infections by MRSA.

Support or Funding Information

NIH
Evidence for female specific changes in the sympathetic nervous system in post‐infarction heart failure
Authors: Pinkham Maximilian I , Pyner Susan , Shenton Fiona C , Whalley Gillian , Habecker Beth , Woodward Bill , Guild Sarah‐Jane I , Barrett Carolyn J
Published: November 2023

The development and progression of post‐myocardial infarction (MI) heart failure is, in part, driven by adverse changes in the sympathetic nervous system (SNS). Clinically, females, compared to males, typically have a worse outcome post‐MI. The aim of these experiments was to characterize changes in the SNS in females and males. All experiments were performed in ovary‐intact female and male Wistar rats. Following MI or sham‐MI surgery, heart failure developed over a 6–8 week period at which time left ventricular (LV) function was assessed before and following the acute infusion of metoprolol, under chloralose‐urethane anesthesia. Following the terminal experiment, brain and heart tissue were collected and processed for histochemical and molecular analyses. Post‐MI, LV function was significantly reduced in both males and females which was associated with cardiomyocyte hypertrophy and increased collagen deposition. The acute infusion of metoprolol decreased arterial pressure significantly less in females with MI (−9±2 mmHg) compared to female sham‐MI group (−21±8 mmHg, P<0.05) and male MI group (−23±3 mmHg, P<0.05). In animals with post‐infarction heart failure, metoprolol decreased cardiac output similarly in males (−33±8 ml/min) and females (−31±7 ml/min); however females responded by significantly increasing total peripheral resistance (TPR) whereas TPR was unchanged in males. In a subset of animals with post‐infarction heart failure, renal sympathetic nerve activity responses to a decrease in arterial pressure were augmented in females but not in males and arterial baroreceptor denervation abolished this response. Compared to sham MI group, LV noradrenaline (NA) tissue content was decreased in males with MI (4.6±0.2 vs. 2.7±0.4 pmol/mg, P<0.05) but was unaltered in females with MI (4.3±0.4 pmol/mg). Post‐infarction heart failure resulted in reduced nNOS levels in the paraventricular nucleus (PVN) in both males and females with MI whereas super oxide dismutase levels were decreased only in males, not females. cFOS levels in the PVN were increased in females with post‐infarction heart failure but decreased in males, possibly related to an augmented baroreflex response in female MI group following the metoprolol mediated decrease in cardiac output. The current findings show that ovary‐intact female rats have similar changes in cardiac function and remodelling in post‐infarction heart failure as males; however there are sex differences in the regulation of the SNS. In particular, these findings suggest sex differences in post‐infarction heart failure particularly in relation to the autonomic regulation of arterial pressure.

Support or Funding Information

This work was supported by grants from the University of Auckland Research and Development Fund and The National Heart Foundation of New Zealand
Moderately High Salt Intake does not Raise Blood Pressure but does Activate Peripheral Immune Cells with the Capacity to Raise Blood Pressure
Authors: ZUBCEVIC Jasenka , Ahmari Niousha , Diaz Devon , Malphurs Wendi , Redlitz Conrad M , Andrade Marry Ann , Toney Glenn M
Published: November 2023

INTRODUCTION

Arterial hypertension (HTN) is often salt sensitive and accompanied by renin‐angiotensin (RAS) and immune system activation. For example, activated T cells contribute significantly to Angiotensin II (Ang II)‐dependent HTN. In a salt‐sensitive model, rats fed a moderately high salt diet (2% NaCl) experience neuroadaptations that increase excitability of PVN sympathetic control neurons without developing overt HTN. Dietary salt is also linked with autoimmune diseases (e.g., psoriatic arthritis, lupus, etc.) that are often co‐morbid with HTN and associated with T cell‐dependent interleukin 17 (IL17) signaling. Here, we hypothesized that elevated dietary salt will increase IL17 expression in T lymphocytes and contribute to the salt‐sensitivity of arterial HTN, possibly by priming of the pre‐sympathetic circuitry.

METHODS

Adult Sprague‐Dawley rats were placed on either a normal (0.4% NaCl) or high salt (2% NaCl) diet for two weeks. Blood and bone marrow (BM) were collected to determine levels of CD4+IL17+ T lymphocytes by FACS. Additionally, adult C57BL/6‐Il17atm1Bcgen/J mice (Jax Labs), with constitutive expression of EGFP as a marker of IL17a activity, were subjected to a similar experimental protocol. Blood pressures (BP) were measured once a week by tail cuff. Whole body fluorescence imaging was performed in all mice to detect group differences in the levels of IL17a. BM was collected both from normal and high salt fed mice, and fluorescence sorting separated IL17+ from IL17‐cells. Adoptive transfer was performed by injecting the same number of harvested cells via tail vein into separate groups of naïve C57BL6/J adult mice (n=6/group). BP was measured twice a week for two weeks following the adoptive transfer.

RESULTS

In rats, high salt intake increased expression of IL17a in BM, but not in circulating CD4+ T cells. There was no change in the total CD4+ T cell population. In mice, whole body fluorescence revealed a ~12% increase of IL17 reporter fluorescence selectively in the head region in the high salt group. We observed a significant increase of systolic BP (113±6 to 135±3 mm Hg; P<0.05) within one week of adoptive transfer of IL17a+ BM cells from the high salt group.

CONCLUSION

A moderately high salt diet is not sufficient to raise BP in the whole animal. Nevertheless, it does activate a population of IL17‐expressing immune cells which alone are capable of raising BP. We speculate that suppression of endogenous RAS by high salt intake might offset or otherwise preclude the pro‐HTN effects of immune cell activation.

Support or Funding Information

AHA14SDG18300010&UFCVM (JZ); NIH HL102310 (GMT)
Phospholamban is a Potential Regulator of Skeletal Muscle and Whole‐Body Metabolism
Authors: Gamu Daniel , Mazereeuw Symon , Tupling A. Russell
Published: November 2023

Phospholamban (PLN) is a known inhibitor of the sarco(endo)plasmic reticulum Ca2+‐ATPase (SERCA) pump and modulator of muscular contractility. We have previously shown that the PLN homologue, sarcolipin, is an uncoupler of SERCA function, increasing the energy demand of skeletal muscle to pump Ca2+. Here, we sought to determine whether PLN has a similar effect on SERCA energetics and metabolism. To examine this, SERCA function and whole‐body metabolic rate were measured in PLN knock‐out mice and wild‐type (WT) littermates (n = 5–6/group). Ca2+‐dependent ATPase activity was measured in left ventricle (LV) and soleus (SOL) homogenates in both the absence (i.e. presence of the Ca2+ ionophore A23187) and presence (i.e. no ionophore) of a Ca2+ gradient. The ionophore ratio, an indication of membrane leak, was calculated by dividing maximal activity in the presence of ionophore by that without. Indirect calorimetry was also used to measure whole‐body metabolic rate. In the presence of ionophore, maximal SERCA activity was 25% and 33% greater with PLN ablation in LV (P < 0.05) and SOL (P < 0.01), respectively, while no differences were found in the absence of ionophore in either LV (P = 0.82) or SOL (P = 0.11). The LV ionophore ratio was 22% lower in WT mice (P < 0.05), suggesting that the presence of PLN is associated with membrane leak. While not statistically significant (P = 0.21), the SOL ionophore ratio was 11% lower in WT mice. Lastly, whole‐body energy expenditure tended (P = 0.07) to be lower with PLN ablation. Together, these findings suggest that PLN may alter SERCA pumping energetics and whole‐body metabolic rate.

Support or Funding Information

Canadian Institutes for Health Research
IL‐15 Promotes Mitochondrial Activity Through an ERK1/2‐PPARδ Signaling Axis in C2C12 Skeletal Muscle Cells
Authors: Abbott Marcia J , Krolopp James E , Nakamoto Ty
Published: November 2023

Myokines are specialized factors that are secreted from skeletal muscle (SKM). Many myokines have been shown to increase in circulation following exercise. In particular, interleukin‐15 (IL‐15) is one such myokine and its expression and secretion is induced with exercise. It has been postulated that IL‐15 induces SKM mitochondrial activity, via activation of PPARδ. However, the direct downstream mediators linking IL‐15 to PPARδ activity have yet to be elucidated. Here we aimed to identify the direct downstream signaling molecules of IL‐15 and their roles in mediating mitochondrial activity in SKM. The SKM cell line, C2C12, was cultured and cells were induced to differentiate into mature myotubes. Upon induction of differentiation, C2C12 cells were treated every other day, for 6 days, with vehicle (DMSO), IL‐15 (100 ng/ml), a PPARδ inhibitor (GSK), or IL‐15 + GSK. Western blotting and qPCR analysis were performed to verify inhibition of PPARδ. To assess mitochondrial activity, cells were stained with Mitotracker, fixed, and imaged at the end of the 6 day protocol. Additional short term experiments were performed on fully differentiated cells that were treated with or without IL‐15 (100 ng/ml) for 24 hours. Subsequently, proteins were extracted and western blotting was performed to assess phosphorylation levels of potential downstream signals of IL‐15 (Jak1, Akt, Akt substrates, and ERK1/2). Additionally, following the 24 hour protocol proteins were extracted and ERK1/2 was immunoprecipitated and western blotting procedures were performed to determine potential PPARδ interaction. PPARδ protein and mRNA expression were increased with IL‐15 treatment and these effects were abolished with GSK. Further, IL‐15 stimulated mitochondrial activity, as indicated by increases in Mitoctracker staining, and IL‐15 + GSK blunted these effects. IL‐15 treatment, for 24 hours, had no effect on phosphorylation or total protein expression of Jak1, Akt, or Akt substrates. However, ERK1/2 phosphorylation was increased with IL‐15, without a concomitant increase in total ERK1/2 expression levels. Moreover, when ERK1/2 was immunoprecipitated, there were higher levels of PPARδ interaction with ERK1/2 (34%; P<0.05), in the IL‐15 treated cells when compared to cells without IL‐15 treatment. Taken together, IL‐15 mediated increases in mitochondrial activity are dependent on PPARδ activity. Here we show, for the first time, that IL‐15 activates ERK1/2 in C2C12 SKM cells. Further, our data indicate that IL‐15 induces interaction between ERK1/2 and PPARδ. Overall, it is clear that IL‐15 acts to regulate mitochondrial activity via an ERK1/2‐PPARδ signaling axis in SKM cells.

Support or Funding Information

Crean College of Health and Behavioral Sciences, Chapman University, Start‐Up Funding