bluuebunny/crossref_metadata_2025 huggingface dataset:
Damping Ratio of Sand Containing Fine Particles in Cyclic Triaxial Liquefaction Tests
Authors: Zhao Jiajing , Zhu Zhehao , Liu Jiaquan , Zhong Huaqiao
Published: April 2023

Sand liquefaction triggered by earthquakes is a devastating geological disaster and has emerged as an engaging topic in earthquake engineering. With an enhanced understanding of pure sand liquefaction promoted by laboratory research, there is a growing concern, following filed investigations, over the influence of fine particles on the liquefaction potential of sand containing inclusions. Efforts have been devoted to clarifying the significance of certain physical indicators (e.g., plasticity index, particle shape and gradation characteristics), and fruitful conclusions can be found in the published literature. However, the relationship between the content of fine particles and the cyclic degradation in liquefaction process seems still unclear. To fill this knowledge gap, three sets of cyclic triaxial tests were performed on various sand–fines mixtures with the dry tamping method. The experimental results revealed that (i) fine particles provided a negative contribution to the global soil structure; (ii) however, the damping ratio measured from the obtained stress–strain loops manifested its independence from the fines content during cyclic degradation. In this paper, we propose a shearing mechanism on the microscopic scale to explain the above contrasting observations. For a given soil fabric, the fine particles around sand-to-sand contact points probably break strong force chains, intensifying the threat of liquefaction. By contrast, these fines play the same role in favouring relative sliding between sand grains during both the loading and unloading stages. As the maximum stored energy and the energy loss per cycle are amplified with the same scaling factor, the damping ratio, defined as the ratio between them, should display a macroscopic invariance in triaxial tests.
Metal Mesh-Based Infrared Transparent EMI Shielding Window with Balanced Shielding Properties over a Wide Frequency Spectrum
Authors: Liang Yuanlong , Huang Xianjun , Wen Kui , Wu Zhaofeng , Yao Lixiang , Pan Jisheng , Liu Wencong , Liu Peiguo
Published: April 2023

Metal mesh films have been shown to be a promising strategy to effectively mitigate the growing issue of electromagnetic interference (EMI) in optoelectronic systems. To achieve superior shielding effectiveness, it is common to increase the thickness of the mesh film. However, mesh-based shielding materials have frequency-dependent shielding effectiveness that decreases as the frequency increases. Simply increasing the thickness of the mesh cannot effectively enhance the EMI shielding effectiveness at high frequencies. This will further lead to challenges such as increased processing difficulties and higher costs. In this paper, we present an infrared transparent electromagnetic shielding window based on metal mesh with irregular patterns and proper thickness. The mesh coating is fabricated on a sapphire substrate using ultraviolet photolithography technology and exhibits an efficient electromagnetic shielding effectiveness of more than 20 dB over the wide frequency range of 1.7–18 GHz while maintaining high infrared optical transparency. More importantly, there is no distinct variation in shielding effectiveness between low and high frequency ranges, demonstrating a balanced shielding characteristic across a broad frequency band. This work could be crucial in designing cost-effective and efficient EMI shielding windows for optoelectronic systems.
Linguistic Methods of Image Division for Visual Data Security
Authors: Ogiela Lidia , Ogiela Marek R.
Published: April 2023

This paper defines new classes of algorithms for securing and sharing visual information. Algorithms offering data protection against unauthorised access are cryptographic protocols for data sharing and splitting. These protocols ensure the division of information among a trusted group of secret holders, with every protocol participant being allocated a specified number of shares in the executed algorithm. Proposing and defining new solutions in the field of cryptographic algorithms for data sharing constitutes the main topic of this paper. This paper discusses a new class of algorithms for secret sharing with the use of linguistic formalisms dedicated to the processes of meaning interpretation and linguistic data sharing. Linguistic threshold schemes serve the processes of data protection in distributed systems; they are also used to distribute the shared secret parts in an optimum way, and to perform the meaning analysis and interpretation of various data sets. Semantic analysis as an element of the impact assessment of the meaning of the interpreted and analysed data will make it possible to take into consideration a much wider aspect of description and interpretation of the analysed phenomenon or data set; it will also enable the assessment of the core of the characterised sets in respect to other information with related meaning. The proposed protocols enhance the security of shared data, and allow the generation of any number of secret shares, which is greater than traditional secret sharing methods.
High-Resolution, Broad-Range Detection Setup for Polarimetric Optical Fiber Sensors
Authors: Wierzba Paweł
Published: April 2023

A common-path polarization interferometer using a Wollaston prism and an area detector for the measurement of retardation or optical path difference is presented. Employing a moderate-resolution 1280 by 1024 pixel monochrome camera, it offers a measurement range of approximately 780 radians at 830 nm and 1350 radians at 515 nm while maintaining a high measurement resolution. Retardation introduced by a zero-order waveplate or a Soleil–Babinet compensator was measured to evaluate the performance of the interferometer. Based on the presented measurement results, the resolution of the measurement is estimated to be better than 0.002 rad.
Optimization of Heat Pump Systems in Buildings by Minimizing Costs and CO2 Emissions
Authors: Vonžudaitė Otilija , Martišauskas Linas , Bakas Rimantas , Urbonienė Sigita , Urbonas Rolandas
Published: April 2023

District heating systems are gaining global recognition as an essential tool for reducing greenhouse gas emissions and transitioning to a low-carbon-energy future. In this context, heat pumps are becoming an important technology, providing an effective solution for improving energy efficiency and reducing the reliance on fossil fuels in heating systems. Therefore, this study is focused on the optimal selection of heat pump systems for different types of buildings considering technical, economic, environmental, and social factors. This paper proposes a novel methodology based on mixed-integer nonlinear programming and multi-objective optimization that minimizes total costs and reduces CO2 emissions for heat production and supply systems over a desired period. The methodology is applied to various building types, including renovated and unrenovated apartment buildings, schools, kindergartens, and a supermarket. The study analyzes various types of heat pumps and electric heaters for space heating and domestic hot water production. Optimization results showed that the optimal heating system includes air-to-water heat pumps and electric heaters. Furthermore, for schools and a supermarket, these systems are combined with hybrid heat pumps. The goal of making the heating system neutral in terms of CO2 emissions was achieved for eight out of eleven buildings analyzed. The most profitable investments were in the heating systems of renovated five-story and unrenovated nine-story apartment buildings due to their low energy costs (0.0831 EUR/kWh), short payback periods, and high returns on investment.
An Intelligent Tool Based on Fuzzy Logic and a 3D Virtual Learning Environment for Disabled Student Academic Performance Assessment
Authors: Elfakki Abir Osman , Sghaier Souhir , Alotaibi Abdullah Alhumaidi
Published: April 2023

In a virtual learning environment, it is important to be able to correctly assess students to help them receive the best possible education. This can have a big impact on the way disabled students learn and their goals for gaining a high level of qualification. This paper investigated different fuzzy logic-based techniques for student academic evaluations in a 3D virtual learning environment (VLE). Some of the techniques were found to be especially helpful for disabled students, and the paper also described the development and design of evaluation systems that take this into account. The study used fuzzy logic to study how well disabled students are doing in their classes over a whole year. This fuzzy logic was developed using MATLAB software, which uses features extracted from student evaluations. Disabled students’ characteristics (such as experience and understanding, problem-solving skills, etc.) have been measured and combined with a 3D virtual learning environment built using open-source software, Moodle, and Sloodle. This way, disabled students can interact with their courses inside a 3D VLE using Sloodle. According to the findings, which were based on 20 disabled students, fuzzy logic technology used in 3D Virtual Learning Environments (VLEs) produces different results than traditional assessments. The difference between the two is about 3.9 points on average.
COVID-19: Rehabilitation Needs, Therapeutic Development, and Impact on the Health System
Authors: de Sire Alessandro , Ammendolia Antonio
Published: April 2023

The COVID-19 pandemic has impacted the health of millions of people worldwide, with many survivors experiencing persistent symptoms and long-term disabilities [...]
RPL-Based IoT Networks under Simple and Complex Routing Security Attacks: An Experimental Study
Authors: Alsukayti Ibrahim S. , Alreshoodi Mohammed
Published: April 2023

Effective security support still remains a challenge even for a standardized Internet of Things network protocol such as the IPv6 Routing Protocol for Low-Power and Lossy Networks (RPL). It provides limited protection against external security attacks but stays highly vulnerable to internal routing attacks. The inherent RPL design of RPL, particularly its topology establishment and maintenance mechanism, makes it easy to initiate such kinds of attacks which target overall network performance and topology stability. Establishing a firm and practical understanding of the impacts of these attacks on RPL networks is still critically needed for further investigation. This is more demanding when considering varying-scale RPL deployments targeted by complex attack scenarios. In this research work, an extensive experimental study of these critical RPL routing attacks considering simple-to-complex attack scenarios in varying-scale RPL network setups is presented. It provides a practical contribution toward experimentally understanding the effectiveness of internal routing attacks when targeting RPL-based IoT networks. The main objective is to provide future research works with a practical reference to the effectiveness of these security attacks and the overall performance of RPL networks under routing attacks. The results indicate the adverse impacts of routing attacks on the overall performance of RPL networks. Even in simple attack scenarios, it was found that the attacked networks experienced noticeable degradation in QoS performance and topology stability. In addition, the attacks incurred considerable increases in energy consumption and control traffic overhead. These were more evident in large-scale experimental setups and also under composite and hybrid routing attacks. QoS performance and topology stability degraded by more than 90% whereas energy consumption and network overhead increased by more than 200%.
Structural Design and Numerical Analysis of Hoisting Device of Test Bed for Aircraft Engine
Authors: Park Hyunbum
Published: April 2023

In this work, a test bed and stand structure were designed for the thrust test of an aircraft. The engine test rig consists of a thrust stand, test bed, transport system, and hoisting device. In this study, structural design and analysis of the stand and bed for engine thrust test equipment were performed. The stand structure supported the engine, and the test bed moved the thrust test equipment and the engine. Structural design loads were defined by analyzing the operating conditions. Structural analysis was performed based on the structural design results. As a result of analyzing the structural safety against thrust, which is the main design load, it was considered to be sufficiently safe. Finally, the target structure was manufactured to verify the design result.
Influences of the Mid-Level Vortex on the Formation of Tropical Cyclone Toraji (2013)
Authors: Chuang Chen-Hao , Hsieh Yi-Huan , Liu Pin-Yen , Teng Hsu-Feng , Lee Cheng-Shang
Published: April 2023

This study analyzes the influences of the mid-level vortex on the formation of Tropical Cyclone Toraji (2013). A rare case of a tropical cyclone that formed near Taiwan involved a mid-level vortex that was a remnant of Tropical Cyclone Kong-Rey (2013). The piecewise potential vorticity inversion method is applied to examine the contribution of the mid-level vortex to the low-level wind field under quasi-balanced conditions. Numerical sensitivity experiments are conducted to quantify the importance of the mid-level vortex on Toraji formation, in which the mid-level vortex is removed with different removing factors (percentages) from the initial field. The results indicate that mid-level positive potential vorticity anomalies significantly contribute to the low-level positive vorticity before Toraji formation. Furthermore, when the removing factors increase in the sensitivity experiments, either the intensity of the simulated low-level vortex or the development trend of pre-Toraji decreases. However, there is no significant relationship between the convection’s magnitude and the intensity of the mid-level vortex. The main difference comes from the mid-level vortex’s intensity, which would result in a greater high-level warm core structure and cause stronger vertical mass flux. In summary, the mid-level vortex plays a critical role in the formation of Toraji. It provides a favorable environment for forming the pre-Toraji vortex by maintaining a high-level warm-core structure, leading to the formation of Toraji.
Vestibular Impairment in Patients with Vestibular Schwannoma: A Journey through the Pitfalls of Current Literature
Authors: Pisani Davide , Gioacchini Federico Maria , Chiarella Giuseppe , Astorina Alessia , Ricciardiello Filippo , Scarpa Alfonso , Re Massimo , Viola Pasquale
Published: April 2023

Vestibular Schwannoma is the most common tumour of Ponto Cerebellar Angle and is capable of strongly impacting the patient’s quality of life. In recent decades, the proposals for the management of the disease have multiplied, just as the diagnostic capacity has improved. While in the past, the primary objective was the preservation of the facial function, and subsequently also of the auditory function, the attention to the vestibular symptomatology, which appears to be one of the main indicators of deterioration of quality of life, is still unsatisfactory. Many authors have tried to provide guidance on the best possible management strategy, but a universally recognized guideline is still lacking. This article offers an overview of the disease and the proposals which have advanced in the last twenty years, evaluating their qualities and defects in a critical reading.
Identification of Critical Genes for Ovine Horn Development Based on Transcriptome during the Embryonic Period
Authors: Luan Yuanyuan , Wu Shangjie , Wang Mingkun , Pu Yabin , Zhao Qianjun , Ma Yuehui , Jiang Lin , He Xiaohong
Published: April 2023

Horns, also known as headgear, are a unique structure of ruminants. As ruminants are globally distributed, the study of horn formation is critical not only for increasing our understanding of natural and sexual selection but also for the breeding of polled sheep breeds to facilitate modern sheep farming. Despite this, a significant number of the underlying genetic pathways in sheep horn remain unclear. In this study, to clarify the gene expression profile of horn buds and investigate the key genes in horn bud formation, RNA-sequencing (RNA-seq) technology was utilized to investigate differential gene expression in the horn buds and adjacent forehead skin of Altay sheep fetuses. There were only 68 differentially expressed genes (DEGs) identified, consisting of 58 up-regulated genes and 10 down-regulated genes. RXFP2 was differentially up-regulated in the horn buds and had the highest significance (p-value = 7.42 × 10−14). In addition, 32 DEGs were horn-related genes identified in previous studies, such as RXFP2, FOXL2, SFRP4, SFRP2, KRT1, KRT10, WNT7B, and WNT3. Further, Gene Ontology (GO) analysis showed that the DEGs were mainly enriched with regard to growth, development, and cell differentiation. Pathway analysis revealed that the Wnt signaling pathway may be responsible for horn development. Further, through combining the protein–protein interaction networks of the DEGs, it was found that the top five hub genes, namely, ACAN, SFRP2, SFRP4, WNT3, and WNT7B, were also associated with horn development. Our results suggest that only a few key genes, including RXFP2, are involved in bud formation. This study not only validates the expression of candidate genes identified at the transcriptome level in previous studies but also provides new possible marker genes for horn development, which may promote our understanding of the genetic mechanisms of horn formation.
Intraoperative Augmented Reality in Microsurgery for Intracranial Arteriovenous Malformation: A Case Report and Literature Review
Authors: Li Chi-Ruei , Shen Chiung-Chyi , Yang Meng-Yin , Tsuei Yuang-Seng , Lee Chung-Hsin
Published: April 2023

Background: Intracranial arteriovenous malformations (AVMs) are lesions containing complex vessels with a lack of buffering capillary architecture which might result in hemorrhagic cerebrovascular accidents (CVAs). Intraoperative navigation can improve resection rates and functional preservation in patients with lesions in eloquent areas, but current systems have limitations that can distract the operator. Augmented Reality (AR) surgical technology can reduce these distractions and provide real-time information regarding vascular morphology and location. Methods: In this case report, an adult patient was admitted to the emergency department after a fall, and diagnostic imaging revealed a Spetzler–Martin grade I AVM in the right parietal region with evidence of rupture. The patient underwent a stereotactic microsurgical resection with assistance from augmented reality technology, which allowed for a hologram of the angioarchitecture to be projected onto the cortical surface, aiding in the recognition of the angiographic anatomy during surgery. Results: The patient’s postoperative recovery went smoothly. At 6-month follow-up, the patient had remained in stable condition, experiencing complete relief from his previous symptoms. The follow-up examination also revealed complete obliteration of the AVMs without any remaining pathological vascular structure. Conclusions: AR-assisted microsurgery makes both the dissection and resection steps safer and more delicate. As several innovations are occurring in AR technology today, it is likely that this novel technique will be increasingly adopted in both surgical applications and education. Although certain limitations exist, this technique may still become more efficient and precise as this novel technology its continues to develop further.
Calibration of Impairment Severity to Enable Comparison across Somatosensory Domains
Authors: Matyas Thomas A. , Mak-Yuen Yvonne Y. K. , Boelsen-Robinson Tristan P. , Carey Leeanne M.
Published: April 2023

Comparison across somatosensory domains, important for clinical and scientific goals, requires prior calibration of impairment severity. Provided test score distributions are comparable across domains, valid comparisons of impairment can be made by reference to score locations in the corresponding distributions (percentile rank or standardized scores). However, this is often not the case. Test score distributions for tactile texture discrimination (n = 174), wrist joint proprioception (n = 112), and haptic object identification (n = 98) obtained from pooled samples of stroke survivors in rehabilitation settings were investigated. The distributions showed substantially different forms, undermining comparative calibration via percentile rank or standardized scores. An alternative approach is to establish comparable locations in the psychophysical score ranges spanning performance from just noticeably impaired to maximally impaired. Several simulation studies and a theoretical analysis were conducted to establish the score distributions expected from completely insensate responders for each domain. Estimates of extreme impairment values suggested by theory, simulation and observed samples were consistent. Using these estimates and previously discovered values for impairment thresholds in each test domain, comparable ranges of impairment from just noticeable to extreme impairment were found. These ranges enable the normalization of the three test scales for comparison in clinical and research settings.
Isogenic Mammary Models of Intraductal Carcinoma Reveal Progression to Invasiveness in the Absence of a Non-Obligatory In Situ Stage
Authors: Bernhardt Sarah M. , Mitchell Elizabeth , Stamnes Stephanie , Hoffmann Reuben J. , Calhoun Andrea , Klug Alex , Russell Tanya D. , Pennock Nathan D. , Walker Joshua M. , Schedin Pepper
Published: April 2023

In breast cancer, progression to invasive ductal carcinoma (IDC) involves interactions between immune, myoepithelial, and tumor cells. Development of IDC can proceed through ductal carcinoma in situ (DCIS), a non-obligate, non-invasive stage, or IDC can develop without evidence of DCIS and these cases associate with poorer prognosis. Tractable, immune-competent mouse models are needed to help delineate distinct mechanisms of local tumor cell invasion and prognostic implications. To address these gaps, we delivered murine mammary carcinoma cell lines directly into the main mammary lactiferous duct of immune-competent mice. Using two strains of immune-competent mice (BALB/c, C57BL/6), one immune-compromised (severe combined immunodeficiency; SCID) C57BL/6 strain, and six different murine mammary cancer cell lines (D2.OR, D2A1, 4T1, EMT6, EO771, Py230), we found early loss of ductal myoepithelial cell differentiation markers p63, α-smooth muscle actin, and calponin, and rapid formation of IDC in the absence of DCIS. Rapid IDC formation also occurred in the absence of adaptive immunity. Combined, these studies demonstrate that loss of myoepithelial barrier function does not require an intact immune system, and suggest that these isogenic murine models may prove a useful tool to study IDC in the absence of a non-obligatory DCIS stage—an under-investigated subset of poor prognostic human breast cancer.
Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer
Authors: Alsabbagh Rama , Ahmed Munazza , Alqudah Mohammad A. Y. , Hamoudi Rifat , Harati Rania
Published: April 2023

Brain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and its incidence is increasing. Brain metastasis occurs through a multi-step cascade where cancer cells spread from the primary tumor site to the brain. The extravasation of tumor cells through the blood–brain barrier (BBB) is a critical step in brain metastasis. During extravasation, circulating cancer cells roll along the brain endothelium (BE), adhere to it, then induce alterations in the endothelial barrier to transmigrate through the BBB and enter the brain. Rolling and adhesion are generally mediated by selectins and adhesion molecules induced by inflammatory mediators, while alterations in the endothelial barrier are mediated by proteolytic enzymes, including matrix metalloproteinase, and the transmigration step mediated by factors, including chemokines. However, the molecular mechanisms mediating extravasation are not yet fully understood. A better understanding of these mechanisms is essential as it may serve as the basis for the development of therapeutic strategies for the prevention or treatment of brain metastases. In this review, we summarize the molecular events that occur during the extravasation of cancer cells through the blood–brain barrier in three types of cancer most likely to develop brain metastasis: breast cancer, melanoma, and lung cancer. Common molecular mechanisms driving extravasation in these different tumors are discussed.
Fecal Microbiota Restoration Modulates the Microbiome in Inflammation-Driven Colorectal Cancer
Authors: Gates Travis J , Yuan Ce , Shetty Mihir , Kaiser Thomas , Nelson Andrew C , Chauhan Aastha , Starr Timothy K , Staley Christopher , Subramanian Subbaya
Published: April 2023

Chronic inflammation of the colon (colitis) is a known risk factor for inflammatory-driven colorectal cancers (id-CRCs), and intestinal microbiota has been implicated in the etiology of id-CRCs. Manipulation of the microbiome is a clinically viable therapeutic approach to limiting id-CRCs. To understand the microbiome changes that occur over time in id-CRCs, we used a mouse model of id-CRCs with the treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS) and measured the microbiome over time. We included cohorts where the microbiome was restored using cage bedding swapping and where the microbiome was depleted using antibiotics to compare to untreated animals. We identified consistent increases in Akkermansia in mice receiving horizontal microbiome transfer (HMT) via cage bedding swapping, while the control cohort had consistent longitudinal increases in Anaeroplasma and Alistipes. Additionally, fecal lipocalin-2 (Lcn-2), a marker of intestinal inflammation, was elevated in unrestored animals compared to restored and antibiotic-treated counterparts following HMT. These observations suggest a potential role for Akkermansia, Anaeroplasma, and Alistipes in regulating colonic inflammation in id-CRCs.
SRSF5 Regulates the Expression of BQ323636.1 to Modulate Tamoxifen Resistance in ER-Positive Breast Cancer
Authors: Tsoi Ho , Fung Nicholas Nok-Ching , Man Ellen P. S. , Leung Man-Hong , You Chan-Ping , Chan Wing-Lok , Chan Sum-Yin , Khoo Ui-Soon
Published: April 2023

About 70% of breast cancer patients are oestrogen receptor-positive (ER +ve). Adjuvant endocrine therapy using tamoxifen (TAM) is an effective approach for preventing local recurrence and metastasis. However, around half of the patients will eventually develop resistance. Overexpression of BQ323636.1 (BQ) is one of the mechanisms that confer TAM resistance. BQ is an alternative splice variant of NCOR2. The inclusion of exon 11 generates mRNA for NCOR2, while the exclusion of exon 11 produces mRNA for BQ. The expression of SRSF5 is low in TAM-resistant breast cancer cells. Modulation of SRSF5 can affect the alternative splicing of NCOR2 to produce BQ. In vitro and in vivo studies confirmed that the knockdown of SRSF5 enhanced BQ expression, and conferred TAM resistance; in contrast, SRSF5 overexpression reduced BQ expression and, thus, reversed TAM resistance. Clinical investigation using a tissue microarray confirmed the inverse correlation of SRSF5 and BQ. Low SRSF5 expression was associated with TAM resistance, local recurrence and metastasis. Survival analyses showed that low SRSF5 expression was associated with poorer prognosis. We showed that SRPK1 can interact with SRSF5 to phosphorylate it. Inhibition of SRPK1 by a small inhibitor, SRPKIN-1, suppressed the phosphorylation of SRSF5. This enhanced the proportion of SRSF5 interacting with exon 11 of NCOR2, reducing the production of BQ mRNA. As expected, SRPKIN-1 reduced TAM resistance. Our study confirms that SRSF5 is essential for BQ expression. Modulating the activity of SRSF5 in ER +ve breast cancer will be a potential approach to combating TAM resistance.
EZH2 and POU2F3 Can Aid in the Distinction of Thymic Carcinoma from Thymoma
Authors: Naso Julia R. , Vrana Julie A. , Koepplin Justin W. , Molina Julian R. , Roden Anja C.
Published: April 2023

Thymic carcinoma is an aggressive malignancy that can be challenging to distinguish from thymoma using histomorphology. We assessed two emerging markers for these entities, EZH2 and POU2F3, and compared them with conventional immunostains. Whole slide sections of 37 thymic carcinomas, 23 type A thymomas, 13 type B3 thymomas, and 8 micronodular thymomas with lymphoid stroma (MNTLS) were immunostained for EZH2, POU2F3, CD117, CD5, TdT, BAP1, and MTAP. POU2F3 (≥10% hotspot staining), CD117, and CD5 showed 100% specificity for thymic carcinoma versus thymoma with 51%, 86%, and 35% sensitivity, respectively, for thymic carcinoma. All POU2F3 positive cases were also positive for CD117. All thymic carcinomas showed >10% EZH2 staining. EZH2 (≥80% staining) had a sensitivity of 81% for thymic carcinoma and a specificity of 100% for thymic carcinoma versus type A thymoma and MNTLS but had poor specificity (46%) for thymic carcinoma versus B3 thymoma. Adding EZH2 to a panel of CD117, TdT, BAP1, and MTAP increased cases with informative results from 67/81 (83%) to 77/81 (95%). Overall, absent EZH2 staining may be useful for excluding thymic carcinoma, diffuse EZH2 staining may help to exclude type A thymoma and MNTLS, and ≥10% POU2F3 staining has excellent specificity for thymic carcinoma versus thymoma.
Comedications with Immune Checkpoint Inhibitors: Involvement of the Microbiota, Impact on Efficacy and Practical Implications
Authors: Colard-Thomas Julien , Thomas Quentin Dominique , Viala Marie
Published: April 2023

Immune checkpoint inhibitors (ICIs) have been a major breakthrough in solid oncology over the past decade. The immune system and the gut microbiota are involved in their complex mechanisms of action. However, drug interactions have been suspected of disrupting the fine equilibrium necessary for optimal ICI efficacy. Thus, clinicians are facing a great deal of sometimes contradictory information on comedications with ICIs and must at times oppose conflicting objectives between oncological response and comorbidities or complications. We compiled in this review published data on the role of the microbiota in ICI efficacy and the impact of comedications. We found mostly concordant results on detrimental action of concurrent corticosteroids, antibiotics, and proton pump inhibitors. The timeframe seems to be an important variable each time to preserve an initial immune priming at ICIs initiation. Other molecules have been associated with improved or impaired ICIs outcomes in pre-clinical models with discordant conclusions in retrospective clinical studies. We gathered the results of the main studies concerning metformin, aspirin, and non-steroidal anti-inflammatory drugs, beta blockers, renin-angiotensin-aldosterone system inhibitors, opioids, and statins. In conclusion, one should always assess the necessity of concomitant treatment according to evidence-based recommendations and discuss the possibility of postponing ICI initiation or switching strategies to preserve the critical window.
Management of Gastro-Intestinal Toxicity of the Pi3 Kinase Inhibitor: Optimizing Future Dosing Strategies
Authors: Breal Claire , Beuvon Frederic , de Witasse-Thezy Thibault , Dermine Solene , Franchi-Rezgui Patricia , Deau-Fisher Benedicte , Willems Lise , Grignano Eric , Contejean Adrien , Bouscary Didier , Faillie Jean Luc , Treluyer Jean-Marc , Guerin Corinne , Chouchana Laurent , Vignon Marguerite
Published: April 2023

The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in cancer progression and in host immunity. Idelalisib was the first of this class to be approved with the second-generation Pi3 kinase inhibitors copanlisib, duvelisib and umbralisib, subsequently being approved in the United States. Real-world data are lacking, however, in relation to the incidence and toxicity of Pi3 kinase inhibitor-induced colitis. We here review, in the first instance, the general landscape of the Pi3K inhibitors in the context of hematological malignancies, with a focus on the adverse gastrointestinal side effects reported by various clinical trials. We further review the available worldwide pharmacovigilance data in relation to these drugs. Finally, we describe our own real-world experience with idelalisib-induced colitis management in our center and in a national setting.
FAK Inhibitor-Based Combinations with MEK or PKC Inhibitors Trigger Synergistic Antitumor Effects in Uveal Melanoma
Authors: Tarin Malcy , Némati Fariba , Decaudin Didier , Canbezdi Christine , Marande Benjamin , Silva Lisseth , Derrien Héloïse , Jochemsen Aart G. , Gardrat Sophie , Piperno-Neumann Sophie , Rodrigues Manuel , Mariani Pascale , Cassoux Nathalie , Stern Marc-Henri , Roman-Roman Sergio , Alsafadi Samar
Published: April 2023

Uveal Melanoma (UM) is a rare and malignant intraocular tumor with dismal prognosis. Even if radiation or surgery permit an efficient control of the primary tumor, up to 50% of patients subsequently develop metastases, mainly in the liver. The treatment of UM metastases is challenging and the patient survival is very poor. The most recurrent event in UM is the activation of Gαq signaling induced by mutations in GNAQ/11. These mutations activate downstream effectors including protein kinase C (PKC) and mitogen-activated protein kinases (MAPK). Clinical trials with inhibitors of these targets have not demonstrated a survival benefit for patients with UM metastasis. Recently, it has been shown that GNAQ promotes YAP activation through the focal adhesion kinase (FAK). Pharmacological inhibition of MEK and FAK showed remarkable synergistic growth-inhibitory effects in UM both in vitro and in vivo. In this study, we have evaluated the synergy of the FAK inhibitor with a series of inhibitors targeting recognized UM deregulated pathways in a panel of cell lines. The combined inhibition of FAK and MEK or PKC had highly synergistic effects by reducing cell viability and inducing apoptosis. Furthermore, we demonstrated that these combinations exert a remarkable in vivo activity in UM patient-derived xenografts. Our study confirms the previously described synergy of the dual inhibition of FAK and MEK and identifies a novel combination of drugs (FAK and PKC inhibitors) as a promising strategy for therapeutic intervention in metastatic UM.
Tamoxifen Affects Aquaporin-3 Expression and Subcellular Localization in Rat and Human Renal Collecting Ducts
Authors: Tingskov Stine Julie , D’Agostino Mariagrazia , Login Frédéric H. , Tamma Grazia , Nejsum Lene N. , Nørregaard Rikke
Published: April 2023

Sex hormones play an important role in the regulation of water homeostasis, and we have previously shown that tamoxifen (TAM), a selective estrogen receptor modulator (SERM), affects the regulation of aquaporin (AQP)-2. In this study, we investigated the effect of TAM on the expression and localization of AQP3 in collecting ducts using various animal, tissue, and cell models. The impact of TAM on AQP3 regulation was studied in rats subjected to 7 days of unilateral ureteral obstruction (UUO), with the rats fed a lithium-containing diet to induce nephrogenic diabetes insipidus (NDI), as well as in human precision-cut kidney slices (PCKS). Moreover, intracellular trafficking of AQP3 after TAM treatment was investigated in Madin-Darby Canine Kidney (MDCK) cells stably expressing AQP3. In all models, the expression of AQP3 was evaluated by Western blotting, immunohistochemistry and qPCR. TAM administration attenuated UUO-induced downregulation of AQP3 and affected the localization of AQP3 in both the UUO model and the lithium-induced NDI model. In parallel, TAM also affected the expression profile of other basolateral proteins, including AQP4 and Na/K-ATPase. In addition, TGF-β and TGF-β+TAM treatment affected the localization of AQP3 in stably transfected MDCK cells, and TAM partly attenuated the reduced AQP3 expression in TGF-β exposed human tissue slices. These findings suggest that TAM attenuates the downregulation of AQP3 in a UUO model and a lithium-induced NDI model and affects the intracellular localization in the collecting ducts.
Impact of Aberrant β-Catenin Pathway on Cholangiocarcinoma Heterogeneity
Authors: Lozano Elisa , Sanchon-Sanchez Paula , Morente-Carrasco Ana , Chinchilla-Tábora Luis Miguel , Mauriz José L. , Fernández-Palanca Paula , Marin Jose J. G. , Macias Rocio I. R.
Published: April 2023

The poor prognosis of most cases of advanced cholangiocarcinoma (CCA) constitutes a severe problem in modern oncology, which is aggravated by the fact that the incidence of this liver cancer is increasing worldwide and is often diagnosed late, when surgical removal is not feasible. The difficulty of dealing with this deadly tumor is augmented by the heterogeneity of CCA subtypes and the complexity of mechanisms involved in enhanced proliferation, apoptosis avoidance, chemoresistance, invasiveness, and metastasis that characterize CCA. Among the regulatory processes implicated in developing these malignant traits, the Wnt/β-catenin pathway plays a pivotal role. Alteration of β-catenin expression and subcellular localization has been associated with worse outcomes in some CCA subtypes. This heterogeneity, which also affects cellular and in vivo models commonly used to study CCA biology and anticancer drug development, must be taken into account for CCA investigation to more accurately extrapolate basic laboratory research to the clinical situation. A better understanding of the altered Wnt/β-catenin pathway in relationship with the heterogeneous forms of CCA is mandatory for developing novel diagnostic tools and therapeutic strategies for patients suffering from this lethal disease.
Prediction of Particle Suspension State for Various Particle Shapes Used in Slug Flow Crystallization
Authors: Kufner Anne Cathrine , Westkämper Nico , Bettin Henrik , Wohlgemuth Kerstin
Published: April 2023

Particle transport is still an immense challenge in many processes today and affects both the operation and the consistency of the product quality, which is essential in the pharmaceutical industry, for example. Therefore, we developed a suspension correlation of particles in the crystallization process for a slug flow crystallizer in the field of small-scale continuous crystallization in this paper to predict and ensure a reproducible process and consistent product quality. Furthermore, the developed suspension correlation shall provide the possibility to perform mechanistic modeling of the agglomeration behavior depending on the operating parameters in the crystallization process. For this purpose, already existing dimensionless numbers were evaluated and modified employing force balances in order to predict the particle behavior in the liquid compartments in the slug flow crystallizer under different operating conditions and particle shapes of the substance system l-alanine/water using L-glutamic acid as impurity during crystallization.
A Multi-Party Functional Signatures Scheme for Private Blockchain
Authors: Zhou Quan , Zheng Yulong , Wei Kaijun , Chen Minhui , Zeng Zhikang
Published: April 2023

Digital signature technology is essential for ensuring the authenticity and unforgeability of transactions in a private blockchain framework. In some scenarios, transactions require verification from multiple parties, each of whom needs to authenticate different parts of the transaction. To address this issue, researchers have developed multi-party ECDSA (Elliptic Curve Digital Signature Algorithm) signature schemes. However, these schemes either need to consider the authentication of different parts of the transaction or generate an aggregated signature. This paper proposes a novel solution that combines functional signatures and multi-party ECDSA signatures to create a multi-party functional signature for private blockchains. Compared to previous constructions, the proposed scheme ensures that each part of the transaction is verified. Furthermore, when the aggregate signature of the entire transaction cannot be verified, this scheme identifies the specific part of the transaction for which the signature authentication fails instead of rejecting the entire transaction. This paper uses a smart contract to securely deploy the proposed scheme and authenticate the f in functional signatures. The constructed scheme also provides security under the existential unforgeability of the ECDSA signature, even if n−1 parties are corrupted, assuming a total of n parties. The scheme of this paper successfully conducted experiments on a personal computer, with three users taking approximately 343 ms, six users taking 552 ms, and nine users taking 791 ms.
Surface Passivation of Germanium with ALD Al2O3: Impact of Composition and Crystallinity of GeOx Interlayer
Authors: Isometsä Joonas , Jahanshah Rad Zahra , Fung Tsun H. , Liu Hanchen , Lehtiö Juha-Pekka , Pasanen Toni P. , Leiviskä Oskari , Miettinen Mikko , Laukkanen Pekka , Kokko Kalevi , Savin Hele , Vähänissi Ville
Published: April 2023

Germanium is an excellent material candidate for various applications, such as field effect transistors and radiation detectors/multijunction solar cells, due to its high carrier mobilities and narrow bandgap, respectively. However, the efficient passivation of germanium surfaces remains challenging. Recently, the most promising results have been achieved with atomic-layer-deposited (ALD) Al2O3, but the obtainable surface recombination velocity (SRV) has been very sensitive to the surface state prior to deposition. Based on X-ray photoelectron spectroscopy (XPS) and low-energy electron diffraction (LEED), we show here that the poor SRV obtained with the combination of HF and DIW surface cleaning and ALD Al2O3 results from a Ge suboxide interlayer (GeOx, x < 2) with compromised quality. Nevertheless, our results also demonstrate that both the composition and crystallinity of this oxide layer can be improved with a combination of low-temperature heating and a 300-Langmuir controlled oxidation in an ultrahigh vacuum (LT-UHV treatment). This results in a reduction in the interface defect density (Dit), allowing us to reach SRV values as low as 10 cm/s. Being compatible with most device processes due to the low thermal budget, the LT-UHV treatment could be easily integrated into many future devices and applications.
Microstructural Evolution and Tensile Properties of a Corrosion-Resistant Ni-Based Superalloys Used for Industrial Gas Turbines
Authors: Gao Zhenhuan , Li Shikun , Liu Gang , Shang Zhao , Song Dazhuo , Yang Gongxian , Zou Juntao , Liang Shuhua
Published: April 2023

As an important mechanical property, tensile behavior has been regarded as an indicator for the creep and thermal mechanical fatigue properties of Ni-based superalloys. The tensile property of Ni-based superalloys is closely related to the amount, size, and distribution of γ'-phase and carbides. To further clarify the tensile deformation mechanism of the CM247LC alloy, this study investigated its solidification characteristics and directionally-solidified and heat-treated microstructure. The dependence of tensile properties on the varied temperature ranging between 650 and 950 ℃ is discussed in detail. It was found that the deformation mechanism at 650 ℃ is dominated by the shearing of dislocations into the γ'-precipitates to form the superlattice stacking faults. At 800 ℃, the K-W lock leads to the anomalous yield effects. At 950 ℃, the deformation mechanism is dominated by the dislocations bypassing the γ'-precipiates. The results provide a comprehensive understanding of the CM247LC alloy and are beneficial for the development of corrosion-resistant Ni-based superalloys.
Decentralized UAV Swarm Scheduling with Constrained Task Exploration Balance
Authors: Chen Runfeng , Li Jie , Peng Ting
Published: April 2023

Scheduling is one of the key technologies used in unmanned aerial vehicle (UAV) swarms. Scheduling determines whether a task can be completed and when the task is complete. The distributed method is a fast way to realize swarm scheduling. It has no central node and UAVs can freely join or leave it, thus making it more robust and flexible. However, the two most representative methods, the Consensus-Based Bundle Algorithm (CBBA) and the Performance Impact (PI) algorithm, pursue the minimum cost impact of tasks, which have optimization limitations and are easily cause task conflicts. In this paper, a new concept called “task consideration” is proposed to quantify the impact of tasks on scheduling and the regression of the task itself, balancing the exploration of the UAV for the minimum-impact task and the regression of neighboring tasks to improve the optimization and convergence of scheduling. In addition, the conflict resolution rules are modified to fit the proposed method, and the exploration of tasks is increased by a new removal method to further improve the optimization. Finally, through extensive Monte Carlo experiments, compared with CBBA and PI, the proposed method is shown to perform better in terms of task allocation and total travel time, and with the increase in the number of average UAV tasks, the number of iterations is less and the convergence is faster.
Diameter Growth of Silver Fir (Abies alba Mill.), Scots Pine (Pinus sylvestris L.), and Black Pine (Pinus nigra Arnold) in Central European Forests: Findings from Slovenia
Authors: Bončina Andrej , Trifković Vasilije , Ficko Andrej
Published: April 2023

The main objectives of the study were to (1) determine the response of the diameter growth of silver fir, Scots pine, and black pine in Central European seminatural forests to tree, stand, and environmental factors and (2) test for differences in their growth rate on different soils. Based on 26,291 permanent sampling plots (500 m² each), we developed a linear mixed-effects model of the diameter increment for each of these tree species. The models explained 32%–47% of the total diameter increment variability. The models differ in the set of predictors. All models suggested a non-linear effect of tree diameter on diameter increment. Nine predictors were common to all three models (stand basal area, quadratic mean diameter, basal area of overtopping trees, the proportion of beech in the stand volume, inclination, elevation, mean annual temperature, mean diurnal range, and soil unit), and six predictors were specific for one or two models (tree diameter, logarithm of tree diameter, proportion of other broadleaves, site productivity, rockiness, eastness index). Tree diameter was the most important variable for fir growth, while climatic variables explained most of the variability in pine diameter growth. The soil unit contributed from 5.3% to 7.5% to the explained diameter increment variability. Although the developed models are only locally accurate and cannot be used outside the study area without validation, the model predictions can be compared to those in other stand growth simulators and other geographical regions.