bluuebunny/crossref_metadata_2025 huggingface dataset:
First‐principles quantum analysis of promising double perovskitesZ2SiF6(Z = K, Li, Na, Rb) as prospective light harvesting materials: Optoelectronic, structural and thermodynamic properties
Authors: Fatima Kisa , Abbas Zeesham , Butt Fabeya , Butt Komal , Hussain Sajjad , Ali Ahsan , Muhammad Shabbir , Algarni H. , Al‐Sehemi Abdullah G.
Published: June 2023

For energy‐efficient and high‐power illumination systems, phosphor materials have attracted huge research attention over the recent decades. Herein, applying the first‐principles method, we investigate and predict the optoelectronic and structural properties of light‐harvesting phosphors Z2SiF6(Z = K, Li, Na, Rb) as promising candidates for weight‐light‐emitting diodes w‐LEDs. The calculated direct energy band gaps are of order 1.56, 1.461, 1.479, and 1.585 eV for Z2SiF6(Z = K, Li, Na, Rb), respectively, thus rendering the compound's semiconducting nature suitable for optoelectronic applications. Calculated structural properties show that Rb2SiF6is the most stable compound among Z2SiF6(Z = K, Li, Na, Rb). The optical properties in the energy range of 0–14 eV have been investigated using the well‐known (GGA) formulism available in the literature. Studied compounds are active optical materials as the value of their refractive index is between 1.0 and 2.0. Based on investigated optical parameters, we can say that Z2SiF6(Z = K, Li, Na, Rb) are potential candidates for optoelectronic device applications like white LEDs (w‐LEDs). Thermodynamic parameters of Z2SiF6(Z = K, Li, Na, Rb) are provided to establish the thermodynamic stability of these compounds.
A novel stochastically stable variational Bayesian Kalman filter for spacecraft attitude estimation
Authors: Qiu Zhenbing , Zhang Jianchun
Published: June 2023

In the context of nonlinear systems, variational Bayesian filters play an important and alternative role to sampling‐based Monte Carlo methods. Although they have been used in conjunction with derivatives of Kalman filters, their behavior, both in terms of convergence, stability, and a solution without a stepwise approximation procedure, has not been well explored. In this paper, we propose a novel, stochastically stable, stepwise approximation‐free variational Bayesian Kalman filter (hence, termed as VBKF) for nonlinear systems. The proposed filter, unlike other posterior distribution estimation methods, is very flexible with the number of parameters that should be known a priori, offers an excellent convergence rate, stochastic stability, and more specifically in its ability to handle non‐Gaussian, unknown, inaccurate and drifting noise models. Furthermore, one of the key advantages of the proposed solution is that it is stepwise approximation‐free, and as such, less computationally demanding. We also prove that the proposed filter is stochastically stable using the Posterior Cramér–Rao Lower Bound. In addition to the stability, by using Lyapunov function, we show that the estimation errors are exponentially bounded by the mean square error under certain conditions. In addition to this, we also demonstrate the practical applicability of the proposed approach by developing a novel filter for estimating the attitude of spacecrafts using star cameras and gyro‐sensors. We then evaluate the efficacy of the novel filter for attitude estimation, and thus that of the VBKF, using a set of detailed simulations mimicking different initialization errors that are common in attitude estimation. Our results show that the proposed approach offers an excellent convergence rate within conventional bounds, better root mean square error when compared against several of the common, and state‐of‐the‐art methods.
Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis
Authors: Go Eun‐Jin , Yang Hannah , Park Wooram , Lee Seung Joon , Han Jun‐Hyeok , Kong So Jung , Lee Won Suk , Han Dong Keun , Chon Hong Jae , Kim Chan
Published: June 2023

Although stimulator of interferon genes (STING) agonists has shown great promise in preclinical studies, the clinical development of STING agonist therapy is challenged by its limited systemic delivery. Here, positively charged fusogenic liposomes loaded with a STING agonist (PoSTING) are designed for systemic delivery and to preferentially target the tumor microenvironment. When PoSTING is administered intravenously, it selectively targets not only tumor cells but also immune and tumor endothelial cells (ECs). In particular, delivery of STING agonists to tumor ECs normalizes abnormal tumor vasculatures, induces intratumoral STING activation, and elicits robust anti‐tumor T cell immunity within the tumor microenvironment. Therefore, PoSTING can be used as a systemic delivery platform to overcome the limitations of using STING agonists in clinical trials.
Optimization of Multi‐Segment Work Roll Profile for 1340 mm HC Tandem Cold‐Rolling Mills Based on DBSCAN and NSGA‐II Algorithms
Authors: Chen Yafei , Peng Lianggui , Feng Pingjie , Zhou Yilin , Li Changsheng
Published: June 2023

To address issues with saturated work roll bending force (WRB), maximum contact pressure between the work roll and intermediate roll (QWI), and challenging flatness lifting in a four‐stand, six‐high tandem cold mill with a 1340 mm width, the density‐based spatial clustering of applications with noise algorithm and the non‐dominated sorting genetic algorithm II are used for optimal design and online application research of a five‐segment work roll profile. When compared to a flat roll and a parabolic roll profile with a maximum crown of 15 μm, the optimized roll profile decreases the secondary crown of the roll gap (CW2) by 5.99 and 1.055 μm, respectively, and the fourth crown of the roll gap (CW4) by 0.21 and 0.39 μm, respectively. Additionally, QWI in the field of roll gap crown adjustment decreases by 1.04 and 0.445 kN mm−1. Industrial testing shows that the average integrated value of flatness in rolling the four extreme specifications of 1340 mm tandem cold‐rolling mills lowers by 2.65 IU following the application of the new roll profile, and the average reduction of WRB in the last stand is 2.215 MPa.
Changes in the distribution of occlusal forces in the course of the orthodontic retention phase
Authors: Fritz F. , Daratsianos N. , Bourauel C. , Papageorgiou Spyridon N. , Jäger A.
Published: June 2023

Purpose

Aim of the present study was to assess the relative distribution of occlusal forces after orthodontic treatment and during the first 3 months of the retention phase using a computerized occlusal analysis system (T-Scan, Tekscan Inc., Norwood, MA, USA).

Materials and methods

A total of 52 patients were included in this prospective cohort study and underwent analysis of occlusal forces on the level of tooth, jaw-half, and -quadrant during a 3-month period. Furthermore, differences between three retention protocols (group I: removable appliances in both jaws; group II: fixed 3–3 lingual retainers in both jaws; group III: removable appliance in the maxilla and fixed 3–3 lingual retainer in mandible) were assessed with Wilcoxon signed-rank tests at 5%.

Results

Directly after debonding, measured forces distribution were similar to published references for untreated samples. In the following, no significant difference was found between retention protocols II and III with regard to the asymmetry of the anterior occlusal forces. Both groups maintained an asymmetric force distribution in the anterior segment during the study period. There was also no difference between groups II and III in the distribution of occlusal forces for the posterior segments. Both retention concepts kept the symmetrical distribution of occlusal forces stable over the observation period. The retention concept of group I demonstrated a symmetrical distribution of occlusal forces in the anterior segment after debonding and this remained stable during the 3‑month period. In the posterior segment, no improvement of the initially asymmetric masticatory force distribution could be observed.

Conclusions

All three studied retention protocols showed stability in retaining their original symmetrical or asymmetrical occlusal force distribution posteriorly/anteriorly during the 3‑month observation period. Therefore, an even distribution of occlusal forces should be the aim of the finishing phase, as no relative benefit of any single retention scheme in terms of post-debond improvement during the retention phase was seen.
Exploration of Evolution-Informed Compassion-Focused Therapy and Buddhist Approaches to Insight Meditation: A Three-Way Exploration
Authors: Gilbert Paul , Huxter Malcolm , Choden
Published: June 2023

This paper explores the overlap and relationship between Compassion-Focused Therapy (CFT) as an evolution-informed, biopsychosocial approach to the mind and two Buddhist approaches to the development of insight and meditation. We present this exploration in terms of a three-way exposition between PG (Paul Gilbert), a clinical psychologist and compassion-focused therapist, MH (Malcolm Huxter), also a clinical psychologist and long-term meditation practitioner, primarily in the Theravada Buddhist traditions, and CH (Choden), a long-term meditation practitioner and monastic of Mahayana Buddhism. We share overlapping but different approaches to the processes of insight, understanding, and the training of compassion.
EMExplorer: an episodic memory enhanced autonomous exploration strategy with Voronoi domain conversion and invalid action masking
Authors: Chen Bolei , Zhong Ping , Cui Yongzheng , Lu Siyi , Liang Yixiong , Sheng Yu
Published: June 2023

Autonomous exploration is a critical technology to realize robotic intelligence as it allows unsupervised preparation for future tasks and facilitates flexible deployment. In this paper, a novel Deep Reinforcement Learning (DRL) based autonomous exploration strategy is proposed to efficiently reduce the unknown area of the workspace and provide accurate 2D map construction for mobile robots. Different from existing human-designed exploration techniques that usually make strong assumptions about the scenarios and the tasks, we utilize a model-free method to directly learn an exploration strategy through trial-and-error interactions with complex environments. To be specific, the Generalized Voronoi Diagram (GVD) is first utilized for domain conversion to obtain a high-dimensional Topological Environmental Representation (TER). Then, the Generalized Voronoi Networks (GVN) with spatial awareness and episodic memory is designed to learn autonomous exploration policies interactively online. For complete and efficient exploration, Invalid Action Masking (IAM) is employed to reshape the configuration space of exploration tasks to cope with the explosion of action space and observation space caused by the expansion of the exploration range. Furthermore, a well-designed reward function is leveraged to guide the learning of policies. Extensive baseline tests and comparative simulations show that our strategy outperforms the state-of-the-art strategies in terms of map quality and exploration speed. Sufficient ablation studies and mobile robot experiments demonstrate the effectiveness and superiority of our strategy.
Evaluation of excavation method on point load strength of rocks with poor geological conditions in a deep metal mine
Authors: Luo Pingkuang , Fang Xugang , Li Diyuan , Yu Yisong , Li Huahua , Cui Peng , Ma Jinyin
Published: June 2023

In the field of deep mining engineering, it poses a challenge to promptly determine the mechanical properties of rocks under poor geological conditions through in-situ tests. However, the indirect determination of uniaxial compressive strength (UCS) of rocks can be achieved through the point load strength index (PLSI) test on irregular samples. In the present study, laboratory uniaxial compressive and field PLSI tests were carried out on irregular ore and rock blocks extracted through mechanical mining methods from a stope at a lead–zinc mine in Yunnan Province, China, with a depth of approximately 1000 m. The effects of mechanical excavation and drilling-blasting methods on the PLSI of rocks and ores are compared. It is found that there are significant differences in the point load strength indexes obtained by different excavation methods, and the Is(50) obtained after the mechanical excavation method approximates the actual value of ore and surrounding rocks. Two correction methods were utilized to obtain the point load strength indexes Is(50)-1 and Is(50)-2 of irregular rock samples. The correlation factors (k) linking Is(50) to UCS and Brazilian splitting strength are derived based on testing results. The findings indicate that using the conversion factor (k) recommended by ISRM to predict the UCS of rocks may significantly underestimate the actual strength of rocks in intricate mining environments. This study can serve as a benchmark for analogous deep mining projects.
Research progresses in O3-type Ni/Fe/Mn based layered cathode materials for sodium ion batteries
Authors: Zhao Shengyu , Shi Qinhao , Feng Wuliang , Liu Yang , Yang Xinxin , Zou Xingli , Lu Xionggang , Zhao Yufeng
Published: June 2023

Sodium ion batteries (SIBs) have attracted great interest as candidates in stationary energy storage systems relying on low cost, high abundance and outstanding electrochemical properties. The foremost challenge in advanced NIBs lies in developing high-performance and low-cost electrode materials. To accelerate the commercialization of sodium ion batteries, various types of materials are being developed to meet the increasing energy demand. O3-type layered oxide cathode materials show great potential for commercial applications due to their high reversible capacity, moderate operating voltage and easy synthesis, while allowing direct matching of the negative electrode to assemble a full battery. Here, representative progress for Ni/Fe/Mn based O3-type cathode materials have been summarized, and existing problems, challenges and solutions are presented. In addition, the effects of irreversible phase transitions, air stability, structural distortion and ion migration on electrochemical performance are systematically discussed. We hope to provide new design ideas or solutions to advance the commercialization of sodium ion batteries.
Alveolar epithelial-like cell differentiation in a dynamic bioreactor: a promising 3D-approach for the high-throughput generation of lung cell types from human induced pluripotent stem cells
Authors: Müller Michelle , Kohl Yvonne , Germann Anja , Wagner Sylvia , Zimmermann Heiko , von Briesen Hagen
Published: June 2023

Purpose

Human induced pluripotent stem cell (hiPSC)-derived lung cell types such as alveolar epithelial cells are promising for toxicological and pharmaceutical in vitro screenings. Reproducible differentiation processes are highly demanded, but protocols which are suitable for the high-throughput generation of lung cell types from hiPSCs are lacking.

Methods

In this study, a new approach for the hiPSC-differentiation in alveolar epithelial-like cells type 2 under dynamic 3D-conditions in a suspension bioreactor is presented. Gene and protein expression analyses of key markers during the embryonal lung development have been performed in comparison to cells differentiated under static 2D-conditions to evaluate the differentiation efficacy of the new bioreactor-based approach. Finally, the resulting cells were infected by SARS-CoV-2 pseudotypes to demonstrate their functionality and suitability for e.g. COVID-19 drug development.

Results

The dynamic bioreactor is suitable to differentiate hiPSCs in spheroids, which express relevant lung markers in each developmental stage on gene and protein level. The 3D method is able to significantly increase the expression of some markers in comparison to conventional 2D differentiation. 3D-differentiated alveolar epithelial-like cells express functional SARS-CoV-2 receptors and can display the viral infection.

Conclusion

The presented dynamic 3D-differentiation is a promising, new approach to generate alveolar epithelial-like cells from hiPSCs as cell source for in vitro lung models.
Climate Change 2022 – Impacts, Adaptation and Vulnerability
Authors: Intergovernmental Panel on Climate Change (IPCC)
Published: June 2023

The Working Group II contribution to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC) provides a comprehensive assessment of the scientific literature relevant to climate change impacts, adaptation and vulnerability. The report recognizes the interactions of climate, ecosystems and biodiversity, and human societies, and integrates across the natural, ecological, social and economic sciences. It emphasizes how efforts in adaptation and in reducing greenhouse gas emissions can come together in a process called climate resilient development, which enables a liveable future for biodiversity and humankind. The IPCC is the leading body for assessing climate change science. IPCC reports are produced in comprehensive, objective and transparent ways, ensuring they reflect the full range of views in the scientific literature. Novel elements include focused topical assessments, and an atlas presenting observed climate change impacts and future risks from global to regional scales. Available as Open Access on Cambridge Core.
Design of a haptic obstacle avoidance for low-speed helicopter operations using active sidesticks
Authors: Walko C. , Müllhäuser M.
Published: June 2023

Helicopter collisions with obstacles are one of the most frequent and most devastating causes of accidents. To avoid these collisions in low-speed operations a “haptic ticker” cue in form of repetitive impulses as a force feedback was designed for an active sidestick. Various design questions were examined in pilot campaigns using a full flight simulator and four test scenarios. As a result, the pilots always knew which distance-based hazard area (green, yellow, red) they were in. Furthermore, the ticker is disruptive and roughly reduces the handling qualities from Level 1 to Level 2. It is therefore primarily activated as a hazard warning and not as a main input to control the distance. As a warning cue the ticker was evaluated as non-disturbing. The force threshold to detect the direction of a tick was determined. With tick strengths above this threshold, the direction is still not recognised at all in around 2% of the ticks. For the remaining ticks, the accuracy with which the direction is recognised is about 15°. In the fourth scenario, obstacles were moved towards the hovering helicopter, potentially forcing a collision. However, with the ticker a collision occurred in less than 4% of the cases, instead of 84% without the ticker. The ticker was rated as very intuitive and worth recommending. When asked how many accidents of this kind could be prevented with this ticker, all five pilots independently estimated 75%.
Navigating the expanded access investigational new drug protocol for tecovirimat: lessons learned from a public–private hospital partnership during the 2022 NYC mpox outbreak
Authors: Mgbako Ofole , Chan Justin , Pitts Robert A. , DiLorenzo Madeline A. , Knutsen Dorothy , Mazo Dana
Published: June 2023

During the 2022 mpox outbreak, tecovirimat was accessed through an expanded access investigational new drug (EA-IND) protocol. We leveraged a unique public/private hospital partnership in New York City to create a novel infrastructure to navigate the EA-IND’s regulatory requirements and rapidly provide tecovirimat to patients.
Translational and angular velocities statistics of inertial prolate ellipsoids in a turbulent channel flow up to Re
τ
= 1000
Authors: Michel Antoine , Arcen Boris
Published: June 2023

Direct numerical simulations of the turbulent flow in a channel are conducted up to

$Re_{\tau }=1000$

to examine the influence of the friction Reynolds number on the translational and angular velocities of inertial, prolate ellipsoids. The quadrant distribution of the turbulent events seen by the particles is not significantly affected by the value of

$Re_{\tau }$

, but subtle modifications take place, depending on the position in the channel and on the particle relaxation time. Overall, the influence of

$Re_{\tau }$

on the first and second statistical moments of the ellipsoids translational velocity is the same as that observed for the fluid velocity. The weak dependence of these statistics to the particle shape previously observed at low Reynolds number remains at higher values of

$Re_{\tau }$

. Similarly, the mean and root mean square (r.m.s.) of the angular velocity of the fluid seen by the particles weakly depend on particle shape and they have the same dependence to

$Re_{\tau }$

as the angular velocity statistics of the carrier fluid. Particle angular velocity statistics are more strongly affected by the flow Reynolds number due to the evolution of the complex shape and inertia dependent rotation orbits with

$Re_{\tau }$

. In the near-wall region the average angular velocity of weakly inertial ellipsoids increases with

$Re_{\tau }$

due to their stronger alignment with the mean fluid vorticity. Furthermore, the r.m.s. of the wall-normal component of the angular velocity of more inertial ellipsoids increases with

$Re_{\tau }$

owing to the larger fluctuations of the angle between the particle major axis and the velocity-gradient plane.
Linear global and asymptotic stability analysis of the flow past rectangular cylinders moving along a wall
Authors: Chiarini Alessandro , Auteri Franco
Published: June 2023

The primary instability of the steady two-dimensional flow past rectangular cylinders moving parallel to a solid wall is studied, as a function of the cylinder length-to-thickness aspect ratio${A{\kern-4pt}R} =L/D$and the dimensionless distance from the wall$g=G/D$. For all${A{\kern-4pt}R}$, two kinds of primary instability are found: a Hopf bifurcation leading to an unsteady two-dimensional flow for$g \ge 0.5$, and a regular bifurcation leading to a steady three-dimensional flow for$g < 0.5$. The critical Reynolds number$Re_{c,2\text{-}D}$of the Hopf bifurcation ($Re=U_\infty D/\nu$, where$U_\infty$is the free stream velocity,$D$the cylinder thickness and$\nu$the kinematic viscosity) changes with the gap height and the aspect ratio. For${A{\kern-4pt}R} \le 1$,$Re_{c,2\text{-}D}$increases monotonically when the gap height is reduced. For${A{\kern-4pt}R} >1$,$Re_{c,2\text{-}D}$decreases when the gap is reduced until$g \approx 1.5$, and then it increases. The critical Reynolds number$Re_{c,3\text{-}D}$of the three-dimensional regular bifurcation decreases monotonically for all${A{\kern-4pt}R}$, when the gap height is reduced below$g < 0.5$. For small gaps,$g < 0.5$, the hyperbolic/elliptic/centrifugal character of the regular instability is investigated by means of a short-wavelength approximation considering pressureless inviscid modes. For elongated cylinders,${A{\kern-4pt}R} > 3$, the closed streamline related to the maximum growth rate is located within the top recirculating region of the wake, and includes the flow region with maximum structural sensitivity; the asymptotic analysis is in very good agreement with the global stability analysis, assessing the inviscid character of the instability. For cylinders with$AR \leq 3$, however, the local analysis fails to predict the three-dimensional regular bifurcation.
On the near-field interaction of vertically offset turbulent plumes
Authors: Richards Megan K. , Coker Oluwaseun E. , Florido Jose , Nicholls Rhiannon A.M. , Ross Andrew N. , Rooney Gabriel G.
Published: June 2023

The flow in and around a pair of plumes from sources that are vertically and horizontally offset is investigated. An analytical potential flow model is developed using an adapted version of the Milne–Thomson circle theorem to represent the flow due to adjacent circular and point sinks. This approximates the horizontal section through offset plumes, which have differing radii at the same vertical position. The predictions of this model are compared against Reynolds-averaged Navier–Stokes (RANS) simulations of the same system. These yield time-averaged results and so are particularly suitable for investigating the relatively weak entrainment field. Single and double plume results from RANS are also presented to compare with known results. Good agreement is found between the features in the analytical model and in the numerical solutions including the location of the stagnation point between the two plumes.
THE STRUCTURAL COMPLEXITY OF MODELS OF ARITHMETIC
Authors: MONTALBÁN ANTONIO , ROSSEGGER DINO
Published: June 2023

We calculate the possible Scott ranks of countable models of Peano arithmetic. We show that no non-standard model can have Scott rank less than

$\omega $

and that non-standard models of true arithmetic must have Scott rank greater than

$\omega $

. Other than that there are no restrictions. By giving a reduction via

$\Delta ^{\mathrm {in}}_{1}$

bi-interpretability from the class of linear orderings to the canonical structural

$\omega $

-jump of models of an arbitrary completion T of

$\mathrm {PA}$

we show that every countable ordinal

$\alpha>\omega $

is realized as the Scott rank of a model of T.
AN EGOCENTRIC LOGIC OF KNOWING HOW TO TELL THEM APART
Authors: NAUMOV PAVEL , TAO JIA
Published: June 2023

Traditionally, the formulae in modal logic express properties of possible worlds. Prior introduced “egocentric” logics that capture properties of agents rather than of possible worlds. In such a setting, the article proposes the modality “know how to tell apart” and gives a complete logical system describing the interplay between this modality and the knowledge modality. An important contribution of this work is a new matrix-based technique for proving completeness theorems in an egocentric setting.
Emancipating human rights: Capitalism and the common good
Authors: Salomon Margot E.
Published: June 2023

This article begins with a study of the political economy of welfare capitalism to demonstrate how the private quest for profit was never going to be undermined by the advance of socio-economic rights. Contrary to the conventional view among human rights lawyers, capital draws power from its rights or welfarism. It is in recognizing the role that socio-economic rights play in serving capitalism that the field of international law concerned with structurally transformative human rights can begin to explore how socio-economic rights inhibit alternative forms of social organization. This work then turns to recovering property rights through a study of recent evictions and housing rights case law of the UN Committee on Economic, Social and Cultural Rights that problematizes structural inequities and calls the financialized capitalist system into question. Next this work investigates radical legal positivism in international indigenous rights jurisprudence for how it transcends the private ownership of indigenous lands and control over the means of production. The social function of property rights is then revisited and extended, drawing to a close an article that unearths how socio-economic rights might yet emancipate people from capitalist property relations, alter the underlying structure of the economy, and, in time, sever its concordance with the capitalist welfare state.
Sea Ice Is Going, but When Will It Be Gone?
Authors: Sidik Saima
Published: June 2023

A pair of studies demonstrate the uncertainty over when the Arctic will become seasonally sea ice free.
A Humid East Asia During the Early Pliocene Indicated by Calcite Nodules From the Chinese Loess Plateau
Authors: Da Jiawei , Breecker Daniel O. , Li Tao , Li Gaojun , Lu Huayu , Ji Junfeng
Published: June 2023

Understanding the monsoonal climate over East Asia during the warm Pliocene, the closest analog of the future warm climate, could better inform us of the regional hydrological responses to global climate change. However, the variations and controlling mechanisms of the regional hydrology during this warm period are not determined due to discrepancies among different proxy‐derived records. Here we apply a multiproxy approach based on the geochemistry of calcite nodules from a Red Clay sequence located on the southern edge of the Chinese Loess Plateau. Both the trace metal/Ca ratios and the carbon and oxygen isotopic compositions of calcite nodules show low values during 5.4–4.1 Ma and increased during 4.1–3.3 Ma, together indicating a humid climate during the early Pliocene, the onset of drying starting at ∼4.1 Ma and further intensification at 3.6 Ma. The timings of these hydrological transitions are consistent with global temperature changes, underlining the crucial role of meridional thermal gradient in shaping the regional hydroclimate over East Asia by modulating the strength and position of the East Asian summer monsoon.
A novel multifunctional radioprotective strategy using P7C3 as a countermeasure against ionizing radiation-induced bone loss
Authors: Wei Fei , Tuong Zewen Kelvin , Omer Mahmoud , Ngo Christopher , Asiatico Jackson , Kinzel Michael , Pugazhendhi Abinaya Sindu , Khaled Annette R. , Ghosh Ranajay , Coathup Melanie
Published: June 2023

Radiotherapy is a critical component of cancer care but can cause osteoporosis and pathological insufficiency fractures in surrounding and otherwise healthy bone. Presently, no effective countermeasure exists, and ionizing radiation-induced bone damage continues to be a substantial source of pain and morbidity. The purpose of this study was to investigate a small molecule aminopropyl carbazole named P7C3 as a novel radioprotective strategy. Our studies revealed that P7C3 repressed ionizing radiation (IR)-induced osteoclastic activity, inhibited adipogenesis, and promoted osteoblastogenesis and mineral deposition in vitro. We also demonstrated that rodents exposed to clinically equivalent hypofractionated levels of IR in vivo develop weakened, osteoporotic bone. However, the administration of P7C3 significantly inhibited osteoclastic activity, lipid formation and bone marrow adiposity and mitigated tissue loss such that bone maintained its area, architecture, and mechanical strength. Our findings revealed significant enhancement of cellular macromolecule metabolic processes, myeloid cell differentiation, and the proteins LRP-4, TAGLN, ILK, and Tollip, with downregulation of GDF-3, SH2B1, and CD200. These proteins are key in favoring osteoblast over adipogenic progenitor differentiation, cell matrix interactions, and shape and motility, facilitating inflammatory resolution, and suppressing osteoclastogenesis, potentially via Wnt/β-catenin signaling. A concern was whether P7C3 afforded similar protection to cancer cells. Preliminarily, and remarkably, at the same protective P7C3 dose, a significant reduction in triple-negative breast cancer and osteosarcoma cell metabolic activity was found in vitro. Together, these results indicate that P7C3 is a previously undiscovered key regulator of adipo-osteogenic progenitor lineage commitment and may serve as a novel multifunctional therapeutic strategy, leaving IR an effective clinical tool while diminishing the risk of adverse post-IR complications. Our data uncover a new approach for the prevention of radiation-induced bone damage, and further work is needed to investigate its ability to selectively drive cancer cell death.
Dissecting the roles of MBD2 isoforms and domains in regulating NuRD complex function during cellular differentiation
Authors: Schmolka Nina , Karemaker Ino D. , Cardoso da Silva Richard , Recchia Davide C. , Spegg Vincent , Bhaskaran Jahnavi , Teske Michael , de Wagenaar Nathalie P. , Altmeyer Matthias , Baubec Tuncay
Published: June 2023

The Nucleosome Remodeling and Deacetylation (NuRD) complex is a crucial regulator of cellular differentiation. Two members of the Methyl-CpG-binding domain (MBD) protein family, MBD2 and MBD3, are known to be integral, but mutually exclusive subunits of the NuRD complex. Several MBD2 and MBD3 isoforms are present in mammalian cells, resulting in distinct MBD-NuRD complexes. Whether these different complexes serve distinct functional activities during differentiation is not fully explored. Based on the essential role of MBD3 in lineage commitment, we systematically investigated a diverse set of MBD2 and MBD3 variants for their potential to rescue the differentiation block observed for mouse embryonic stem cells (ESCs) lacking MBD3. While MBD3 is indeed crucial for ESC differentiation to neuronal cells, it functions independently of its MBD domain. We further identify that MBD2 isoforms can replace MBD3 during lineage commitment, however with different potential. Full-length MBD2a only partially rescues the differentiation block, while MBD2b, an isoform lacking an N-terminal GR-rich repeat, fully rescues the Mbd3 KO phenotype. In case of MBD2a, we further show that removing the methylated DNA binding capacity or the GR-rich repeat enables full redundancy to MBD3, highlighting the synergistic requirements for these domains in diversifying NuRD complex function.
Genetic associations with parental investment from conception to wealth inheritance in six cohorts
Authors: Wertz Jasmin , Moffitt Terrie E. , Arseneault Louise , Barnes J. C. , Boivin Michel , Corcoran David L. , Danese Andrea , Hancox Robert J. , Harrington HonaLee , Houts Renate M. , Langevin Stephanie , Liu Hexuan , Poulton Richie , Sugden Karen , Tanksley Peter T. , Williams Benjamin S. , Caspi Avshalom
Published: June 2023

Genetic inheritance is not the only way parents’ genes may affect children. It is also possible that parents’ genes are associated with investments into children’s development. We examined evidence for links between parental genetics and parental investments, from the prenatal period through to adulthood, using data from six population-based cohorts in the UK, US and New Zealand, together totalling 36,566 parents. Our findings revealed associations between parental genetics—summarized in a genome-wide polygenic score—and parental behaviour across development, from smoking in pregnancy, breastfeeding in infancy, parenting in childhood and adolescence, to leaving a wealth inheritance to adult children. Effect sizes tended to be small at any given time point, ranging from RR = 1.12 (95% confidence interval (95%CI) 1.09, 1.15) to RR = 0.76 (95%CI 0.72, 0.80) during the prenatal period and infancy; β = 0.07 (95%CI 0.04, 0.11) to β = 0.29 (95%CI 0.27, 0.32) in childhood and adolescence, and RR = 1.04 (95%CI 1.01, 1.06) to RR = 1.11 (95%CI 1.07, 1.15) in adulthood. There was evidence for accumulating effects across development, ranging from β = 0.15 (95%CI 0.11, 0.18) to β = 0.23 (95%CI 0.16, 0.29) depending on cohort. Our findings are consistent with the interpretation that parents pass on advantages to offspring not only via direct genetic transmission or purely environmental paths, but also via genetic associations with parental investment from conception to wealth inheritance.
Repurposing and computational design of PARP inhibitors as SARS-CoV-2 inhibitors
Authors: Rampogu Shailima , Jung Tae Sung , Ha Min Woo , Lee Keun Woo
Published: June 2023

Coronavirus disease 2019 (COVID-19) is a recent pandemic that caused serious global emergency. To identify new and effective therapeutics, we employed a drug repurposing approach. The poly (ADP ribose) polymerase inhibitors were used for this purpose and were repurposed against the main protease (Mpro) target of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). The results from these studies were used to design compounds using the ‘Grow Scaffold’ modules available on Discovery Studio v2018. The three designed compounds, olaparib 1826 and olaparib 1885, and rucaparib 184 demonstrated better CDOCKER docking scores for Mpro than their parent compounds. Moreover, the compounds adhered to Lipinski’s rule of five and demonstrated a synthetic accessibility score of 3.55, 3.63, and 4.30 for olaparib 1826, olaparib 1885, and rucaparib 184, respectively. The short-range Coulombic and Lennard-Jones potentials also support the potential binding of the modified compounds to Mpro. Therefore, we propose these three compounds as novel SARS-CoV-2 inhibitors.
Exogenous AMPA downregulates gamma-frequency network oscillation in CA3 of rat hippocampal slices
Authors: Li Chengzhang , Li Zhenrong , Xu Sihan , Jiang Sanwei , Ye Zhenli , Yu Bin , Gong Shixiang , Li Junmei , Hu Qilin , Feng Bingyan , Wang Mengmeng , Lu Chengbiao
Published: June 2023

Pharmacologically-induced persistent hippocampal γ oscillation in area CA3 requires activation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs). However, we demonstrated that exogenous AMPA dose-dependently inhibited carbachol (CCH)-induced γ oscillation in the CA3 area of rat hippocampal slices, but the underlying mechanism is not clear. Application of AMPARs antagonist NBQX (1 μM) did not affect γ oscillation power (γ power), nor AMPA-mediated γ power reduction. At 3 μM, NBQX had no effect on γ power but largely blocked AMPA-mediated γ power reduction. Ca2+-permeable AMPA receptor (CP-AMPAR) antagonist IEM1460 or CaMKK inhibitor STO-609 but not CaMKIIα inhibitor KN93 enhanced γ power, indicating that activation of CP-AMPAR or CaMKK negatively modulated CCH-induced γ oscillation. Either CP-AMPAR antagonist or CaMKK inhibitor alone did not affected AMPA-mediated γ power reduction, but co-administration of IEM1460 and NBQX (1 μM) largely prevented AMPA-mediated downregulation of γ suggesting that CP-AMPARs and CI-AMPARs are involved in AMPA downregulation of γ oscillation. The recurrent excitation recorded at CA3 stratum pyramidale was significantly reduced by AMPA application. Our results indicate that AMPA downregulation of γ oscillation may be related to the reduced recurrent excitation within CA3 local neuronal network due to rapid CI-AMPAR and CP-AMPAR activation.
Influenza transmissibility among patients and health-care professionals in a geriatric short-stay unit using individual contact data
Authors: Gustin Marie-Paule , Pujo-Menjouet Laurent , Vanhems Philippe
Published: June 2023

Detailed information are lacking on influenza transmissibility in hospital although clusters are regularly reported. In this pilot study, our goal was to estimate the transmission rate of H3N2 2012-influenza, among patients and health care professionals in a short-term Acute Care for the Elderly Unit by using a stochastic approach and a simple susceptible-exposed-infectious-removed model. Transmission parameters were derived from documented individual contact data collected by Radio Frequency IDentification technology at the epidemic peak. From our model, nurses appeared to transmit infection to a patient more frequently with a transmission rate of 1.04 per day on average compared to 0.38 from medical doctors. This transmission rate was 0.34 between nurses. These results, even obtained in this specific context, might give a relevant insight of the influenza dynamics in hospitals and will help to improve and to target control measures for preventing nosocomial transmission of influenza. The investigation of nosocomial transmission of SARS-COV-2 might gain from similar approaches.
Small mammals reduce activity during high moon illumination under risk of predation by introduced predators
Authors: Taylor P. , Swan M. , Sitters H. , Smith A. , Di Stefano J.
Published: June 2023

Predation influences prey survival and drives evolution of anti-predator behaviour. Anti-predator strategies by prey are stimulated by direct encounters with predators, but also by exposure to indicators of risk such as moonlight illumination and vegetation cover. Many prey species will suffer increased risk on moonlit nights, but risk may be reduced by the presence of dense vegetation. Determining the role of vegetation in reducing perceived risk is important, especially given predictions of increased global wildfire, which consumes vegetation and increases predation. We used remote cameras in southeastern Australia to compare support for the predation risk and habitat-mediated predation risk hypotheses. We examined the influence of moonlight and understorey cover on seven 20–2500 g mammalian prey species and two introduced predators, red foxes and feral cats. Activity of all prey species reduced by 40–70% with increasing moonlight, while one species (bush rat) reduced activity in response to increasing moonlight more sharply in low compared to high understorey cover. Neither predator responded to moonlight. Our findings supported the predation risk hypothesis and provided limited support for the habitat-mediated predation risk hypothesis. For prey, perceived costs of increased predation risk on moonlit nights outweighed any benefits of a brighter foraging environment.
A procedure and model for the identification of uni- and biarticular structures passive contribution to inter-segmental dynamics
Authors: Koussou Axel , Dumas Raphaël , Desailly Eric
Published: June 2023

Inter-segmental moments come from muscles contractions, but also from passive moments, resulting from the resistance of the periarticular structures. To quantify the passive contribution of uni- and biarticular structures during gait, we propose an innovative procedure and model. 12 typically developed (TD) children and 17 with cerebral palsy (CP) participated in a passive testing protocol. The relaxed lower limb joints were manipulated through full ranges of motion while kinematics and applied forces were simultaneously measured. The relationships between uni-/biarticular passive moments/forces and joint angles/musculo-tendon lengths were modelled by a set of exponential functions. Then, subject specific gait joint angles/musculo-tendon lengths were input into the determined passive models to estimate joint moments and power attributable to passive structures. We found that passive mechanisms contribute substantially in both populations, mainly during push-off and swing phases for hip and knee and push-off for the ankle, with a distinction between uni- and biarticular structures. CP children showed comparable passive mechanisms but larger variability than the TD ones and higher contributions. The proposed procedure and model enable a comprehensive assessment of the passive mechanisms for a subject-specific treatment of the stiffness implying gait disorders by targeting when and how passive forces are impacting gait.
Applying cosmetic oil with added aromatic compounds improves tactile sensitivity and skin properties
Authors: Samain-Aupic Léonard , Gilbert Laura , André Nathalie , Ackerley Rochelle , Ribot-Ciscar Edith , Aimonetti Jean-Marc
Published: June 2023

Tactile sensitivity generally decreases with aging and is associated with impairments in skin properties. Products that hydrate the skin can combat touch deficits and aromatic compounds have been shown to improve skin mechanical properties. Thus, we tested a base cosmetic oil against a perfumed oil, applied to the skin of females aged 40–60 years, on tactile sensitivity and skin properties after repeated application. Tactile detection thresholds were assessed using calibrated monofilaments applied at the index finger, palm, forearm, and cheek. Spatial discrimination on the finger was assessed using pairs of plates with different inter-band spaces. These tests were performed before and after 1 month of base or perfumed oil use. We found that tactile detection thresholds and spatial discrimination improved only in perfumed oil group. A complementary immunohistological study using human skin was conducted to estimate the expression of olfactory receptor OR2A4 and elastic fiber length. Further, the expression of OR2A4 intensity and the length of elastic fibers increased significantly with oil application, where larger effects were seen with the perfumed oil. We conclude that the application of a perfumed oil may be of additional benefit and could repair, and even prevent, tactile decline with aging by ameliorating skin condition.
Reasons for high prevalence of contraceptive withdrawal in Tehran, Iran
Authors: Erfani Amir , Kolahi Ali-Asghar
Published: June 2023

This study explores reasons for withdrawal use that is highly prevalent in Iran. A face-to-face semi-structured survey questionnaire was designed and 79 married women aged 15–49, who were only using withdrawal when attending five primary healthcare centers in Tehran during September–October 2021 were interviewed. Results showed that withdrawal mostly was chosen by the couple (67%), and partly by the woman alone (19%) or by the husband alone (14%). Participants evaluated withdrawal positively that has no side effect and cost, is easy to use and accessible, and increases sexual pleasure and intimacy. Most women agreed that husbands use withdrawal to protect their wife's health (76%). Women obtained contraceptive information primarily from gynecologists (42%), the internet (21%), midwives in public health centers (19%), and social networks (18%). "Side effects of modern methods" (37%), "fear of side effects" (16%), and "reduction in sexual pleasure" (14%) were the major reasons reported for using withdrawal. While 'side effects' was given mostly by women who alone or with their husband chose withdrawal (52%, 38%), 'reduction in sexual pleasure' and 'fear of side effects' were mostly reported by women whose husband was the sole decision maker in choosing withdrawal (28%, 25%). The 'fear of side effects' was reported mostly by women who had lower education (21%), used the internet for contraceptive information (23%), and whose husband alone chose withdrawal (25%). Cost of modern methods was a trivial reason for using withdrawal. Most withdrawal users (75%) would not switch to modern methods even if they were freely accessible. More educated women and their husbands would be less likely to switch to modern methods even they were provided freely (OR 0.28, CI 0.10–0.80; OR 0.20, CI 0.07–0.59). However, women who were using modern methods before, and those who alone chose withdrawal would be more likely to switch to modern methods (OR 6.4, CI 2.0–20.2; OR 3.4, CI 1.1–11.2). Access to regular contraceptive counselling and public health campaigns could help women to deal with fears of side effects of modern methods, learn their proper use, and to receive education on how to use withdrawal more effectively to avoid unintended pregnancies.
Stabilizer codes for open quantum systems
Authors: Pereira Francisco Revson F. , Mancini Stefano , La Guardia Giuliano G.
Published: June 2023

The Lindblad master equation describes the evolution of a large variety of open quantum systems. An important property of some open quantum systems is the existence of decoherence-free subspaces. A quantum state from a decoherence-free subspace will evolve unitarily. However, there is no procedural and optimal method for constructing a decoherence-free subspace. In this paper, we develop tools for constructing decoherence-free stabilizer codes for open quantum systems governed by the Lindblad master equation. This is done by pursuing an extension of the stabilizer formalism beyond the celebrated group structure of Pauli error operators. We then show how to utilize decoherence-free stabilizer codes in quantum metrology in order to attain the Heisenberg limit scaling with low computational complexity.