bluuebunny/crossref_metadata_2025 huggingface dataset:
Unwinding the SARS-CoV-2 Ribosomal Frameshifting Pseudoknot with LNA and G-Clamp-Modified Phosphorothioate Oligonucleotides Inhibits Viral Replication
Authors: Knizhnik Ekaterina , Chumakov Stepan , Svetlova Julia , Pavlova Iulia , Khodarovich Yuri , Brylev Vladimir , Severov Vjacheslav , Alieva Rugiya , Kozlovskaya Liubov , Andreev Dmitry , Aralov Andrey , Varizhuk Anna
Published: November 2023

Ribosomal frameshifting (RFS) at the slippery site of SARS-CoV-2 RNA is essential for the biosynthesis of the viral replication machinery. It requires the formation of a pseudoknot (PK) structure near the slippery site and can be inhibited by PK-disrupting oligonucleotide-based antivirals. We obtained and compared three types of such antiviral candidates, namely locked nucleic acids (LNA), LNA–DNA gapmers, and G-clamp-containing phosphorothioates (CPSs) complementary to PK stems. Using optical and electrophoretic methods, we showed that stem 2-targeting oligonucleotide analogs induced PK unfolding at nanomolar concentrations, and this effect was particularly pronounced in the case of LNA. For the leading PK-unfolding LNA and CPS oligonucleotide analogs, we also demonstrated dose-dependent RSF inhibition in dual luciferase assays (DLAs). Finally, we showed that the leading oligonucleotide analogs reduced SARS-CoV-2 replication at subtoxic concentrations in the nanomolar range in two human cell lines. Our findings highlight the promise of PK targeting, illustrate the advantages and limitations of various types of DNA modifications and may promote the future development of oligonucleotide-based antivirals.
A Comparison of Forest Biomass and Conventional Harvesting Effects on Estimated Erosion, Best Management Practice Implementation, Ground Cover, and Residual Woody Debris in Virginia
Authors: Garren Austin M. , Bolding Michael Chad , Barrett Scott M. , Hawks Eric M. , Aust Wallace Michael , Coates Thomas Adam
Published: November 2023

Expanding markets for renewable energy feedstocks have increased demand for woody biomass. Concerns associated with forest biomass harvesting include increased erosion, the applicability of conventional forestry Best Management Practices (BMPs) for protecting water quality, and reduced woody debris retention for soil nutrients and cover. We regionally compared the data and results from three prior independent studies that estimated erosion, BMP implementation, and residual woody debris following biomass and conventional forest harvests in the Mountains, Piedmont, and Coastal Plain of Virginia. Estimated erosion was higher in the Mountains due to steep slopes and operational challenges. Mountain skid trails were particularly concerning, comprising only 8.47% of the total area but from 37.9 to 81.1% of the total site-wide estimated erosion. BMP implementation varied by region and harvest type, with biomass sites having better implementation than conventional sites, and conventional Mountain sites having lower implementation than other regions. Sufficient woody debris remained for BMPs on both harvest types in all regions, with conventional Mountain sites retaining twice that of Coastal Plain sites. BMPs reduced the estimated erosion on both site types suggesting increased implementation could reduce potential erosion in problematic areas. Therefore, proper BMP implementation should be ensured, particularly in Mountainous terrain, regardless of harvest type.
Combination Therapy of RAS Inhibition and SGLT2 Inhibitors Decreases Levels of Endotrophin in Persons with Type 2 Diabetes
Authors: Møller Alexandra Louise , Thöni Stefanie , Keller Felix , Sharifli Samir , Rasmussen Daniel Guldager Kring , Genovese Federica , Karsdal Morten Asser , Mayer Gert
Published: November 2023

We investigated for the first time the effect of combination therapy of renin–angiotensin system inhibition (RASi) and sodium–glucose co-transporter-2 inhibitors (SGLT2is) on endotrophin (ETP), a pro-fibrotic signaling molecule reflecting collagen type VI formation, measured in the plasma of persons with type 2 diabetes (T2D). ETP was measured using the PRO-C6 ELISA in 294 individuals from the “Drug combinations for rewriting trajectories of renal pathologies in type 2 diabetes” (DC-ren) project. In the DC-ren study, kidney disease progression was defined as a >10% decline in the estimated glomerular filtration rate (eGFR) to an eGFR < 60 mL/min/1.73 m2. Among the investigated circulating markers, ETP was the most significant predictor of future eGFR. Combination therapy of RASi and SGLT2is led to a significant reduction in ETP levels compared to RASi monotherapy (p for slope difference = 0.002). Higher levels of baseline plasma ETP were associated with a significantly increased risk of kidney disease progression (p = 0.007). In conclusion, plasma ETP identified individuals at higher risk of kidney disease progression. The observed decreased levels of plasma ETP with combination therapy of RASi and SGLT2is in persons with T2D may reflect a reduced risk of kidney disease progression following treatment with SGLT2is.
Neuropsychological Aspects of Children’s Somatic Disorders in Chronic Diseases: Diabetes and Short Stature in the Developmental Period
Authors: Stanisławska-Kubiak Maia , Wiecheć Katarzyna , Majewska Katarzyna Anna , Teusz Grażyna , Mojs Ewa , Kędzia Andrzej
Published: November 2023

Intellectual functioning studies carried out amongst children indicate that chronic diseases like type 1 diabetes and growth hormone deficiency (GHD), may, but do not necessarily, result in intellectual loss. Cognitive functions may decline as a child becomes older, as a disease persists over time and/or due to non-compliance with treatment recommendations or high stress levels. This study aimed to assess the cognitive functioning of children and youths with T1D and GHD-related short stature compared to healthy children. Methods: The study was carried out on 88 children with type 1 diabetes, 38 children suffering from short stature caused by (GHD), as well as a control group comprising 40 healthy children. Weschler’s tests were applied to measure intellectual and cognitive functions. Results: The results suggest that for children suffering from type 1 diabetes and short stature, their chronic childhood diseases per se do not impair cognitive development. It was observed that the higher the age of chronically ill children and the longer the disease persists, the lower their scores in individual cognitive subtests. For healthy children, age is correlated with the acquisition of particular skills and higher scores in specific subtests. Conclusions: On the basis of qualitative analysis of the cognitive functions subject to the study and close clinical observation of chronically ill children, we have been able to conclude that chronic diseases may alter cognitive functioning.
Detection of Reverse Transcriptase LAMP-Amplified Nucleic Acid from Oropharyngeal Viral Swab Samples Using Biotinylated DNA Probes through a Lateral Flow Assay
Authors: Agarwal Saloni , Hamidizadeh Mojdeh , Bier Frank F.
Published: November 2023

This study focuses on three key aspects: (a) crude throat swab samples in a viral transport medium (VTM) as templates for RT-LAMP reactions; (b) a biotinylated DNA probe with enhanced specificity for LFA readouts; and (c) a digital semi-quantification of LFA readouts. Throat swab samples from SARS-CoV-2 positive and negative patients were used in their crude (no cleaning or pre-treatment) forms for the RT-LAMP reaction. The samples were heat-inactivated but not treated for any kind of nucleic acid extraction or purification. The RT-LAMP (20 min processing time) product was read out by an LFA approach using two labels: FITC and biotin. FITC was enzymatically incorporated into the RT-LAMP amplicon with the LF-LAMP primer, and biotin was introduced using biotinylated DNA probes, specifically for the amplicon region after RT-LAMP amplification. This assay setup with biotinylated DNA probe-based LFA readouts of the RT-LAMP amplicon was 98.11% sensitive and 96.15% specific. The LFA result was further analysed by a smartphone-based IVD device, wherein the T-line intensity was recorded. The LFA T-line intensity was then correlated with the qRT-PCR Ct value of the positive swab samples. A digital semi-quantification of RT-LAMP-LFA was reported with a correlation coefficient of R2 = 0.702. The overall RT-LAMP-LFA assay time was recorded to be 35 min with a LoD of three RNA copies/µL (Ct-33). With these three advancements, the nucleic acid testing-point of care technique (NAT-POCT) is exemplified as a versatile biosensor platform with great potential and applicability for the detection of pathogens without the need for sample storage, transportation, or pre-processing.
Increased Inhibition May Contribute to Maintaining Normal Network Function in the Ventral Hippocampus of a Fmr1-Targeted Transgenic Rat Model of Fragile X Syndrome
Authors: Leontiadis Leonidas J. , Trompoukis George , Felemegkas Panagiotis , Tsotsokou Giota , Miliou Athina , Papatheodoropoulos Costas
Published: November 2023

A common neurobiological mechanism in several neurodevelopmental disorders, including fragile X syndrome (FXS), is alterations in the balance between excitation and inhibition in the brain. It is thought that in the hippocampus, as in other brain regions, FXS is associated with increased excitability and reduced inhibition. However, it is still not known whether these changes apply to both the dorsal and ventral hippocampus, which appear to be differently involved in neurodegenerative disorders. Using a Fmr1 knock-out (KO) rat model of FXS, we found increased neuronal excitability in both the dorsal and ventral KO hippocampus and increased excitatory synaptic transmission in the dorsal hippocampus. Interestingly, synaptic inhibition is significantly increased in the ventral but not the dorsal KO hippocampus. Furthermore, the ventral KO hippocampus displays increased expression of the α1GABAA receptor subtype and a remarkably reduced rate of epileptiform discharges induced by magnesium-free medium. In contrast, the dorsal KO hippocampus displays an increased rate of epileptiform discharges and similar expression of α1GABAA receptors compared with the dorsal WT hippocampus. Blockade of α5GABAA receptors by L-655,708 did not affect epileptiform discharges in any genotype or hippocampal segment, and the expression of α5GABAA receptors did not differ between WT and KO hippocampus. These results suggest that the increased excitability of the dorsal KO hippocampus contributes to its heightened tendency to epileptiform discharges, while the increased phasic inhibition in the Fmr1-KO ventral hippocampus may represent a homeostatic mechanism that compensates for the increased excitability reducing its vulnerability to epileptic activity.
Decrease in Cerebral Blood Flow after Reoxygenation Is Associated with Neurological Syndrome Sequelae and Blood Pressure
Authors: Liu Yanqiu , Yuan Fengjuan , Peng Zhongwei , Zhan Yadong , Lin Jianzhong , Zhang Ran , Zhang Jiaxing
Published: November 2023

Changes in cerebral blood flow (CBF) and regulation of cerebral circulation occur at high altitude (HA). However, the changes in CBF and their associations with neurological syndrome sequelae and blood pressure after subjects return to the lowlands remain unclear. In this study, the subjects were 23 college students who were teaching at an altitude of 4300 m for 30 days. These subjects were studied before reaching the HA (Test 1), one week after returning to the lowlands (Test 2), and three months after returning to the lowlands (Test 3). Symptom scores for de-acclimatization syndrome were evaluated. Changes in CBF were measured using the magnetic resonance imaging arterial spin labeling (ASL) technique. Additionally, the velocity of CBF in the cerebral arteries was measured using a transcranial doppler (TCD). In Test 2 vs. Test 1, the peak systolic velocity and mean velocity in the basilar artery were significantly decreased. CBF exhibited significant decreases in the left putamen/cerebellum crus1/vermis and right thalamus/inferior temporal gyrus, while significant increases were observed in the left postcentral gyrus/precuneus and right middle cingulate gyrus/superior frontal gyrus. In Test 3 vs. Test 1, the basilar artery velocity returned to the baseline level, while CBF continued to decrease. The mean global CBF showed a decreasing trend from Test 1 to Test 3. Furthermore, the mean global CBF had a negative correlation with the systolic pressure, pulse pressure, and mean arterial pressure. The decrease in CBF after reoxygenation may underlie the neurological symptoms in subjects returning to the lowlands. Increased blood pressure could serve as a predictor of a decrease in CBF.
Promoting the Low-Carbon Transition of Power Construction Projects under MRV: An Evolutionary Game Analysis
Authors: Li Lihong , Zhu Rui , Song Kun , Zhang Ou , Jiang Xue
Published: November 2023

The actual situation of carbon-emission reduction in China’s power sector has not yet achieved the expected benefits. The rent-seeking behavior of participants in power construction projects (PCPs) hinders the realization of low-carbon benefits. It is necessary to explore the behavioral strategies of the various participants in the low-carbon transition of PCPs. This paper creatively constructs an evolutionary game model of PCPs’ participants from the perspective of MRV (monitoring, reporting, and verification) and introduces the influence of the public to provide a comprehensive analysis of strategic equilibrium points. Through numerical simulations with MATLAB R2021a software, this paper explores the strategic choices of participants in different situations and gives relevant inferences and proofs. The results show that the grid company dominates at the initial stage and promotes participants to regulate behaviors. Under the premise of satisfying the system-stability requirements, setting the growth rate of the grid company’s punishments to 100% can enhance the willingness for strict supervision, while the growth rate of the supervision costs to 200% significantly decreases the probability of strict supervision. With the integration of MRV and PCPs, participants spontaneously fulfill the carbon-emission-reduction tasks. Reasonable control of input costs can effectively avoid the occurrence of rent-seeking behavior. In addition, this paper sets the public-influence growth rate at 200% and finds that the public plays a greater role in driving participants to fulfill responsibilities. Based on the results, a low-carbon transition mechanism for PCPs under the MRV system is proposed by considering several dimensions, which provides suggestions for participants to fulfill carbon-reduction responsibilities.
Party Wall Behaviour and Impact in QUB and Coheating Tests
Authors: Collett Mark , Hardy Adam , Meulemans Johann , Glew David
Published: November 2023

In situ measurement can enable accurate evaluation of a building’s as-built performance. However, when measuring whole house performance, party walls introduce measurement uncertainty. Subsequently, it is common to “adjust” measurements to isolate heat transfer through party walls. This study explores the behaviour and impact of party walls in QUB and coheating measurements of a semi-detached house, presenting empirical evidence on the validity of these measurements where a party wall is present. Two different party wall heat transfer behaviours were observed through heat flux density measurements. Thermal charging is apparent in QUB tests and the initial stages of coheating. After 48 h of coheating, the party wall has become heat saturated and exhibits stable heat transfer. Consequently, using heat flux density measurements to isolate party wall heat transfer in QUB tests, where thermal saturation has not been achieved, can result in misleading inferences. The coheating and QUB measurements without party wall adjustment are in close agreement, irrespective of differing heating patterns in the neighbouring property. The generalisation of these findings is problematic since they describe the impact of the case study-specific built form and the test conditions. Future work to explore the impact of built form and test conditions is needed.
Experimental Study on the Mechanical Properties of Reinforced Pervious Concrete
Authors: Lee Ming-Gin , Wang Yung-Chih , Wang Wei-Chien , Chien Hung-Jen , Cheng Li-Chi
Published: November 2023

Pervious concrete (PC) has gained popularity as an environmentally friendly solution for mitigating the urban heat island effect and promoting sustainable construction. However, its lower compressive strength, attributed to its higher porosity required for permeability, poses challenges for withstanding heavy vehicle loads on pavements. Our study aims to improve the flexural strength of regular PC by adding advanced reinforcing materials like steel wire mesh or glass fiber mesh. This results in reinforced pervious concrete, referred to as RPC, which offers enhanced strength and durability. The primary objective of our research is to investigate the mechanical behavior of RPC, with a specific emphasis on essential design parameters such as PC elastic modulus, modulus of rupture, and stress–strain characteristics under both single and repeated loading conditions. Our findings reveal that the influence of repeated loading on the compressive strength and elastic modulus of PC pavement is negligible, as there are no significant differences observed between the two loading protocols. Notably, our statistical analysis indicates that the PC strength (fc′) averages around 15 MPa. Moreover, empirical formulas for the elastic modulus (Ec = 3072fc′) and modulus of rupture (fr = 0.86fc′) are derived from our research. Furthermore, our study establishes that the stress–strain behavior of PC closely aligns with the general concrete model proposed by a previous scholar, providing valuable insights into the material’s structural performance. These findings contribute to a better understanding of RPC’s mechanical properties and offer potential solutions for improving its suitability for heavier vehicular loads.
Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations
Authors: Jun Soojin , Park Sehhoon , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Ahn Myung-Ju , Cho Juhee , Jung Hyun Ae
Published: November 2023

Introduction: While the efficacy of immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC) patients with actionable genetic alterations (AGAs) is modest, certain patients demonstrate improved survival. Thus, this study aimed to evaluate the benefits of ICIs in NSCLC patients with diverse AGAs and verify the predictive biomarkers of ICI efficacy. Methods: From January 2018 to July 2022, this study compared the progression-free survival (PFS) of NSCLC patients with different AGAs treated with ICI monotherapy as second- or later-line therapy at Samsung Medical Center. To ascertain the predictors of ICIs efficacy, we adjusted ICIs’ effects on PFS in terms of clinical and molecular biomarkers. Results: EGFR (46.0%) was the most prevalent mutation in 324 patients. In multivariate analysis, PD-L1 positivity (tumor proportion score (TPS) ≥ 1%) (HR = 0.41) and the use of steroids for immune-related adverse events (HR = 0.46) were positive factors for ICI therapy in the AGAs group. Co-existing mutation of STK11 with KRAS mutation (HR = 4.53) and TP53 with MET mutation (HR = 9.78) was negatively associated with survival. Conclusions: The efficacy of ICI treatment varied across AGA subtypes, but patients with KRAS, MET, and BRAF mutations demonstrated relatively long-duration benefits of ICI therapy. PD-L1 was a significant positive predictive biomarker in all AGA groups.
The m7G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK Signaling
Authors: Xie Jiancong , Mo Taiwei , Li Ruibing , Zhang Hao , Liang Guanzhan , Ma Tao , Chen Jing , Xie Hanlin , Wen Xiaofeng , Hu Tuo , Xian Zhenyu , Pan Weidong
Published: November 2023

PDAC is one of the most common malignant tumors worldwide. The difficulty of early diagnosis and lack of effective treatment are the main reasons for its poor prognosis. Therefore, it is urgent to identify novel diagnostic and therapeutic targets for PDAC patients. The m7G methylation is a common type of RNA modification that plays a pivotal role in regulating tumor development. However, the correlation between m7G regulatory genes and PDAC progression remains unclear. By integrating gene expression and related clinical information of PDAC patients from TCGA and GEO cohorts, m7G binding protein NCBP2 was found to be highly expressed in PDAC patients. More importantly, PDAC patients with high NCBP2 expression had a worse prognosis. Stable NCBP2-knockdown and overexpression PDAC cell lines were constructed to further perform in-vitro and in-vivo experiments. NCBP2-knockdown significantly inhibited PDAC cell proliferation, while overexpression of NCBP2 dramatically promoted PDAC cell growth. Mechanistically, NCBP2 enhanced the translation of c-JUN, which in turn activated MEK/ERK signaling to promote PDAC progression. In conclusion, our study reveals that m7G reader NCBP2 promotes PDAC progression by activating MEK/ERK pathway, which could serve as a novel therapeutic target for PDAC patients.
SMYD3 Modulates AMPK-mTOR Signaling Balance in Cancer Cell Response to DNA Damage
Authors: Lepore Signorile Martina , Sanese Paola , Di Nicola Elisabetta , Fasano Candida , Forte Giovanna , De Marco Katia , Disciglio Vittoria , Latrofa Marialaura , Pantaleo Antonino , Varchi Greta , Del Rio Alberto , Grossi Valentina , Simone Cristiano
Published: November 2023

Cells respond to DNA damage by activating a complex array of signaling networks, which include the AMPK and mTOR pathways. After DNA double-strand breakage, ATM, a core component of the DNA repair system, activates the AMPK-TSC2 pathway, leading to the inhibition of the mTOR cascade. Recently, we showed that both AMPK and mTOR interact with SMYD3, a methyltransferase involved in DNA damage response. In this study, through extensive molecular characterization of gastrointestinal and breast cancer cells, we found that SMYD3 is part of a multiprotein complex that is involved in DNA damage response and also comprises AMPK and mTOR. In particular, upon exposure to the double-strand break-inducing agent neocarzinostatin, SMYD3 pharmacological inhibition suppressed AMPK cascade activation and thereby promoted the mTOR pathway, which reveals the central role played by SMYD3 in the modulation of AMPK-mTOR signaling balance during cancer cell response to DNA double-strand breaks. Moreover, we found that SMYD3 can methylate AMPK at the evolutionarily conserved residues Lys411 and Lys424. Overall, our data revealed that SMYD3 can act as a bridge between the AMPK and mTOR pathways upon neocarzinostatin-induced DNA damage in gastrointestinal and breast cancer cells.
Coextrusion of Clay-Based Composites: Using a Multi-Material Approach to Achieve Gradient Porosity in 3D-Printed Ceramics
Authors: Jauk Julian , Vašatko Hana , Gosch Lukas , Ristoski Kristijan , Füssl Josef , Stavric Milena
Published: November 2023

3D printing of ceramics has started gaining traction in architecture over the past decades. However, many existing paste-based extrusion techniques have not yet been adapted or made feasible in ceramics. A notable example is coextrusion, a common approach to extruding multiple materials simultaneously when 3D-printing thermoplastics or concrete. In this study, coextrusion was utilized to enable multi-material 3D printing of ceramic elements, aiming to achieve functionally graded porosities at an architectural scale. The research presented in this paper was carried out in two consecutive phases: (1) The development of hardware components, such as distinct material mixtures and a dual extruder setup including a custom nozzle, along with software environments suitable for printing gradient materials. (2) Material experiments including material testing and the production of exemplary prototypes. Among the various potential applications discussed, the developed coextrusion method for clay-based composites was utilized to fabricate ceramic objects with varying material properties. This was achieved by introducing a combustible as a variable additive while printing, resulting in a gradient porosity in the object after firing. The research’s originality can be summarized as the development of clay-based material mixtures encompassing porosity agents for 3D printing, along with comprehensive material-specific printing parameter settings for various compositions, which collectively enable the successful creation of functionally graded architectural building elements. These studies are expected to broaden the scope of 3D-printed clay in architecture, as it allows for performance optimization in terms of structural performance, insulation, humidity regulation, water absorption and acoustics.
Behavioral and Mental Health Problems in Children
Authors: Yang Tingzhong , Wu Dan
Published: November 2023

The stimulus, stress, and behavioral and mental response (SSB) model proposes that various stimuli induce stress and behavioral responses, which may, in turn, lead to health problems [...]
Phylogenetics Study to Compare Chloroplast Genomes in Four Magnoliaceae Species
Authors: Zhao Jianyun , Chen Hu , Li Gaiping , Jumaturti Maimaiti Aisha , Yao Xiaomin , Hu Ying
Published: November 2023

Magnoliaceae, a family of perennial woody plants, contains several endangered species whose taxonomic status remains ambiguous. The study of chloroplast genome information can help in the protection of Magnoliaceae plants and confirmation of their phylogenetic relationships. In this study, the chloroplast genomes were sequenced, assembled, and annotated in Woonyoungia septentrionalis and three Michelia species (Michelia champaca, Michelia figo, and Michelia macclurei). Comparative analyses of genomic characteristics, repetitive sequences, and sequence differences were performed among the four Magnoliaceae plants, and phylogenetic relationships were constructed with twenty different magnolia species. The length of the chloroplast genomes varied among the four studied species ranging from 159,838 bp (Woonyoungia septentrionalis) to 160,127 bp (Michelia macclurei). Four distinct hotspot regions were identified based on nucleotide polymorphism analysis. They were petA-psbJ, psbJ-psbE, ndhD-ndhE, and rps15-ycf1. These gene fragments may be developed and utilized as new molecular marker primers. By using Liriodendron tulipifera and Liriodendron chinense as outgroups reference, a phylogenetic tree of the four Magnoliaceae species and eighteen other Magnoliaceae species was constructed with the method of Shared Coding Sequences (CDS). Results showed that the endangered species, W. septentrionalis, is relatively genetically distinct from the other three species, indicating the different phylogenetic processes among Magnoliaceae plants. Therefore, further genetic information is required to determine the relationships within Magnoliaceae. Overall, complete chloroplast genome sequences for four Magnoliaceae species reported in this paper have shed more light on phylogenetic relationships within the botanical group.
Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development
Authors: Kimura Kotohiko , Jackson Tiffany L. B. , Huang Ru Chih C.
Published: November 2023

Specificity protein 1 (SP1), hypoxia-inducible factor 1 (HIF-1), and MYC are important transcription factors (TFs). SP1, a constitutively expressed housekeeping gene, regulates diverse yet distinct biological activities; MYC is a master regulator of all key cellular activities including cell metabolism and proliferation; and HIF-1, whose protein level is rapidly increased when the local tissue oxygen concentration decreases, functions as a mediator of hypoxic signals. Systems analyses of the regulatory networks in cancer have shown that SP1, HIF-1, and MYC belong to a group of TFs that function as master regulators of cancer. Therefore, the contributions of these TFs are crucial to the development of cancer. SP1, HIF-1, and MYC are often overexpressed in tumors, which indicates the importance of their roles in the development of cancer. Thus, proper manipulation of SP1, HIF-1, and MYC by appropriate agents could have a strong negative impact on cancer development. Under these circumstances, these TFs have naturally become major targets for anticancer drug development. Accordingly, there are currently many SP1 or HIF-1 inhibitors available; however, designing efficient MYC inhibitors has been extremely difficult. Studies have shown that SP1, HIF-1, and MYC modulate the expression of each other and collaborate to regulate the expression of numerous genes. In this review, we provide an overview of the interactions and collaborations of SP1, HIF1A, and MYC in the regulation of various cancer-related genes, and their potential implications in the development of anticancer therapy.
Combined Spectroscopy System Utilizing Gas Electron Multiplier and Timepix3 Technology for Laser Plasma Experiments
Authors: De Leo Veronica , Claps Gerardo , Cordella Francesco , Cristoforetti Gabriele , Gizzi Leonida Antonio , Koester Petra , Pacella Danilo , Tamburrino Antonella
Published: November 2023

We present an innovative X-ray spectroscopy system to address the complex study of the X-ray emissions arising from laser–target interactions, where the emissions occur within extremely brief intervals from femtoseconds to nanoseconds. Our system combines a Gas Electron Multiplier (GEM) detector with a silicon-based Timepix3 (TPX3) detector. These detectors work in tandem, allowing for a spectroscopic radiation analysis along the same line of sight. With an active area of 10 × 10 cm2, the GEM detector allows for 1D measurements for X-ray energies (2–50 keV) by utilizing the full 10 cm gas depth. The high-energy part of the radiation beam exits through a downstream side window of the GEM without being absorbed in the gas volume. Positioned side-on at the GEM detector’s exit, the TPX3 detector, equipped with a pixelated sensor (55 µm × 55 µm; active area 14 mm × 14 mm), uses its full 14 mm silicon sensor to detect hard X-rays (50–500 keV) and gamma rays (0.5–10 MeV). We demonstrate the correct operation of the entire detection system and provide a detailed description of the Timepix3 detector’s calibration procedure, highlighting the suitability of the combined system to work in laser plasma facilities.
The Implementation of MuDirac in Geant4: A Preliminary Approach to the Improvement of the Simulation of the Muonic Atom Cascade Process
Authors: Cataldo Matteo , Cremonesi Oliviero , Pozzi Stefano , Mocchiutti Emiliano , Sarkar Ritabrata , Hillier Adrian D. , Clemenza Massimiliano
Published: November 2023

Muonic Atom X-ray Emission spectroscopy (µ-XES) is a novel elemental technique that exploits the high-energy X-rays emitted from the muonic atom cascade process to characterize materials. At the ISIS Neutron and Muon Source, the technique is performed at Port4 of the RIKEN-RAL facility, with a user demand that is increasing every year. To cope with this demand, it is necessary to continue to improve the method, either for the hardware (detectors, acquisition, etc.) or software (data analysis and interpretation). In both cases, Monte Carlo codes play an important role: with a simulation, it is possible to reproduce the experimental setup and provide a reliable quantitative analysis. In this work, we investigate the capabilities of GEANT4 for such applications. From the results, we observed that the generation of X-rays, especially the kα and kβ transition for high Z atoms, are not in agreement with the experimental ones. A solution to this issue, other than an attempt with a small modification of the GEANT4 cascade class, could be provided by a database of transition energy calculated by a Dirac equation software called MuDirac. The software, developed by the UKRI scientific computing department and the ISIS muon group, can compute all the transition energy for a given nuclide. Here, preliminary results of the implementation of the MuDirac database in GEANT4 are reported.
Molecular Discrimination and Phylogenetic Relationships of Physalis Species Based on ITS2 and rbcL DNA Barcode Sequence
Authors: Pere Katherine , Mburu Kenneth , Muge Edward K. , Wagacha John Maina , Nyaboga Evans N.
Published: November 2023

Plants of the genus Physalis are of economic interest because of their fleshy edible fruits with high nutritional value. Some species have high medicinal value with a long history of ethno-medicinal use to treat diverse diseases. There is therefore a need to correctly discriminate the different species of Physalis for proper utilization. Although most Physalis species have unique morphologies, their vegetative stages are identical, making it difficult to accurately identify them based on morphological characteristics. DNA barcoding has the potential to discriminate species accurately. In this study, ribulose bisphosphate carboxylase large (rbcL) and internal transcribed spacer 2 (ITS2) regions were used to discriminate Physalis species and to reveal their phylogenetic relationships and genetic diversity. Physalis plant samples were collected from seven counties in Kenya based on the availability of the germplasm. The voucher specimens were identified using the botanical taxonomy method and were deposited in the University of Nairobi herbarium. Genomic DNA was isolated from leaf samples of 64 Physalis accessions and used for PCR amplification and the sequencing of rbcL and ITS2 barcode regions. The discriminatory ability of the barcodes was based on BLASTn comparison, phylogenetic reconstruction and cluster analysis, and the determination of inter- and intra-specific distances. The nucleotide polymorphism, genetic diversity and distance of the identified Physalis species were determined using DnaSP and MEGA 11.0 software. Species discrimination was more robust using ITS2 sequences. The species identified and discriminated by ITS2 sequences were Physalis purpurea, Physalis peruviana and Physalis cordata. The rbcL sequences were only able to identify Physalis to the genus level. There was high interspecific and low intraspecific divergence within the identified Physalis species based on ITS2 sequences. The ITS2 barcode is an ideal DNA barcode for use in the discrimination of species, as well as in genetic diversity studies of Physalis accessions in Kenya.
Self-Assembled La0.67Sr0.33MnO3:CeO2 Vertically Aligned Nanocomposite Thin Films on Flexible Mica
Authors: Tian Hongxia , Zhang Xiong , Alodhayb Abdullah , Wang Feng , Jian Jie , Huang Jijie
Published: November 2023

Vertically aligned nanocomposite (VAN) thin film has attracted tremendous research interests owing to its multifunctionality, enhanced physical properties and multi-field coupling. However, VAN has rarely been demonstrated in flexible form, which hinders its further application in flexible devices. In this work, La0.67Sr0.33MnO3-CeO2 (LC) VAN film has been deposited on flexible mica with or without a buffer layer. The LC nanocomposite films show high quality following textured growth and form a typical, vertically aligned nanostructure. Magnetic, transport and magnetoresistance properties have been explored for flexible nanocomposite thin films. Furthermore, flexible LC films maintain their properties after numerous mechanical bending tests, presenting promising future applications in flexible electronics and spintronics.
Field Experiment for a Prequalification Scheme for a Distribution System Operator on Distributed Energy Resource Aggregations
Authors: Park Jung-Sung , Kim Bal-Ho
Published: November 2023

The purpose of this paper is to summarize and share the field experiment results of KEPCO’s project consortium to create a TSO-DSO-DERA interaction scheme. The field experiment was conducted based on the prequalification algorithm proposed in previous research from the same consortium, and was designed to verify the validity of the algorithm under realistic grid conditions. In addition, during the course of the field experiment, it was found that points that were missed or not given much importance in the existing prequalification algorithm could affect the completeness of the overall system, and then practical improvements were made to improve this. The demonstration results confirm that the proposed algorithm is effective in real-world grid environments and can help DSOs to ensure the reliability of the distribution system while supporting DERA’s participation in the wholesale market using the proposed prequalification scheme.
Comment on Roman-Filip et al. Non-Aneurysmal Perimesencephalic Subarachnoid Hemorrhage: A Literature Review. Diagnostics 2023, 13, 1195
Authors: Malhotra Ajay
Published: November 2023

We would like to congratulate Roman-Filip et al. on their recent review on perimesencephalic hemorrhages [...]
A Collaborative Approach to Support Participation in Physical Recreation for Preschool Students with Multiple Disabilities: A Case Series
Authors: Brossman Heather L. , Chiarello Lisa A. , Palisano Robert J. , Wynarczuk Kimberly D.
Published: November 2023

Aims: To evaluate a collaborative participation-based therapy approach for two preschool students with multiple disabilities from the experience of Individualized Education Program (IEP) teams, highlighting the perspective of the physical therapist. Methods: The phases of collaborative participation-based therapy were implemented: (a) collaborative relationships were developed and supported within the IEP teams, (b) collaborative meaningful physical recreation goals were developed for participation at school, (c) strengths and needs assessments using the “Collaborative Process for Action Plans to Achieve Participation Goals” were conducted with IEP teams, (d) participation-based interventions were provided, and (e) goal achievement and processes were evaluated. The use of technology for collaboration was encouraged. The physical therapist kept intervention logs and wrote reflective journal entries. Interventions adhered to COVID-19 regulations. Goal achievement was measured using Goal Attainment Scaling. IEP team members completed questionnaires on their experiences. Results: One student met their goal expectation, and one student exceeded their goal expectation. The students were engaged, and IEP team members’ experiences were positive. Conclusions: The use of participation-based therapy is meaningful, feasible, and acceptable to IEP teams. Team collaboration and flexibility were instrumental to successful implementation. Strategies to promote effective communication and the use of technology would support a participation-based therapy approach.
Teaching Kindness and Compassion: An Exploratory Intervention Study to Support Young Children’s Prosocial Skills in an Inclusive ECEC Setting
Authors: Pardon Katri , Kuusisto Arniika , Uusitalo Lotta
Published: November 2023

In this exploratory intervention study, the aim was to teach 5–7-year-old children prosocial skills in an inclusive Finnish early childhood education and care (ECEC) setting. The intervention programme was based on previous studies and helps fill a gap in how to promote prosocial behaviour in an ECEC setting encompassing children with diverse needs. The theoretical framework draws on research on character strengths in the field of positive psychology, particularly what the literature refers to as the strengths of the heart, namely kindness and compassion. The study follows the methodological framework of pragmatism and a mixed-methods research perspective. Research methods include questionnaires and interviews with children (n = 23), some of their guardians (n = 8) and ECEC teachers (n = 2). The results were two-fold. With the picture-based questionnaire, the pre–post measures showed little advancement. However, individual interviews revealed developments in children’s prosocial thinking that also translated into concrete actions. These findings were further supported by the positive feedback received from teachers and guardians. The contents of the programme can be integrated into daily, inclusive ECEC pedagogy. Methodologically, the intervention design serves as a starting point for the further development of data collection practices that capture children’s voices in ECEC.
Promoting Interdisciplinary Research Collaboration among Mathematics and Special Education Researchers
Authors: Lannin John K. , Rodrigues Jessica , van Garderen Delinda , Lei Qingli , Singell Emily L. , Karim Salima
Published: November 2023

This manuscript provides a theoretical framing of a collaborative research design effort among mathematics education and special education researchers. To gain insight into the current state of research on mathematics learning, we drew on how researchers in mathematics education and special education have defined and operationalized the term ‘mathematical concept’ related to the learning of fractions. Using this information, we designed a future study that focuses on and connects prior research in mathematics and special education. We conclude by discussing the implications of such collaborative research efforts.
Academic Emotions and Regulation Strategies: Interaction with Higher Education Dropout Ideation
Authors: Enguídanos Daniel , Aroztegui Javier , Iglesias-Soilán Manuel , Sánchez-San-José Irene , Fernández Juan
Published: November 2023

(1) Introduction: This article addresses the relationship between students’ emotional experiences—mediated by their regulation strategies—and their intention of dropping out. (2) Materials and Methods: An ad hoc questionnaire was designed based on Pekrun’s Control-Value Theory of Achievement Emotions focusing on three different settings (study, classroom, and exam). Data were collected from 2183 university students. Descriptive, frequency, and correlation analysis were conducted. Also, linear regression analyses and scatter plots were performed. A comparative regression analysis was used with the aim of facilitating the understanding of the mediating effect of emotional regulation strategies. (3) Results: Academic emotions were found to have a significant impact on dropout ideation. The effects of emotional regulation strategies as significant moderators in this relationship were observed, exhibiting variations depending on the context. (4) Discussion: Dropout ideation escalates in the presence of elevated levels of unpleasant emotions and diminished levels of pleasant emotions. The utility of possessing effective emotional regulation strategies becomes evident in mitigating dropout ideation during emotionally challenging academic situations.
Development of a Heuristic Control Algorithm for Improving Energy Efficiency in Commercial Refrigerated Systems without Indoor Information
Authors: Kwon Ji-Hoon , Kim Man-Ho , Lee Ju-Kyoung , Kim Hyeong-Jun , Min Seon-Gyu , Lee Suk
Published: November 2023

Despite the serious threat of global warming caused by carbon emissions, commercial refrigeration systems that generate cooling are unable to adjust their usage time. Therefore, it is essential to enhance the energy efficiency of refrigeration systems themselves. Recently developed refrigeration systems offer improved energy consumption efficiency as they utilize inverter-type outdoor units that can communicate with indoor units. However, traditional legacy refrigeration systems still suffer from poor energy efficiency because the existing indoor units cannot communicate with inverter-type outdoor units. Hence, this paper introduces a heuristic energy efficiency improvement algorithm for commercial refrigeration systems using legacy indoor units when an inverter-type outdoor unit is installed. In particular, to reduce the computational complexity of the process of selecting the optimal temperature difference and target low-pressure variables that can enhance energy efficiency, the algorithm employs the Monte Carlo method. Finally, the performance of the proposed heuristic energy efficiency improvement algorithm was evaluated in a laboratory environment to confirm its applicability.
Optimization of Rural Demand-Responsive Transportation through Transfer Point Allocation
Authors: Martí Pasqual , Jordán Jaume , De la Prieta Fernando , Julian Vicente
Published: November 2023

Rural mobility has a lack of innovative proposals in contrast with its urban counterpart. This research aims to bring solutions that ease the implementation of reliable and flexible rural transportation. Demand-responsive transportation is chosen to develop a public transportation service providing interurban trips among several rural settlements. Given the characteristics of rural displacement demand, a novel approach is introduced to optimize the service’s economic costs: the dynamic transfer point allocation. The problem is fully formulated and an architecture is introduced describing the workflow of the whole system. Data from an interurban bus transportation service are used to build a case study of a rural area of Valencia, Spain, and develop several examples illustrating the benefits of the proposed approach. The results reveal that the dynamic creation of transfer points can simplify the transportation fleet’s itineraries and boost the amount of served travel requests. Finally, a discussion of the benefits and dangers of flexible features in rural transportation is developed, underscoring the need to achieve a balance between dynamic operation and service quality.
Color Remote Sensing Image Restoration through Singular-Spectra-Derived Self-Similarity Metrics
Authors: Xu Xudong , Zhang Zhihua , Crabbe M. James C.
Published: November 2023

Color remote sensing images have key features of pronounced internal similarity characterized by numerous repetitive local patterns, so the capacity to effectively harness these self-similarity features plays a key role in the enhancement of color images. The main novelty of this study lies in that we utilized an unusual technique (singular spectrum) to derive brand-new similarity metrics inside the quaternion representation of color images and then incorporated these metrics into denoising algorithms. Color image denoising experiments demonstrated that compared with seven mainstream image restoration algorithms (homomorphic filtering (HPF), wavelet transforms (WT), non-local means (NLM), non-local total variation (NLTV), the color adaptation of non-local means (NLMC), quaternion Euclidean metric (QNLM), and quaternion Euclidean metric total variation (QNLTV)), our algorithms with two novel self-similarity metrics achieved maximum peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), average gradient (AG), and information entropy index (IE) values, with average increases of 1.98 dB /2.12 dB, 0.1168/0.1244, 1.824/1.897, and 0.158/0.135. Moreover, for a complex, mixed-noise scenario, two versions of our algorithms also achieved average increases of 0.382 dB/0.394 dB and 0.0207/0.0210 under Motion and Gaussian mixed noise and average increases of 0.129 dB/0.154 dB and 0.0154/0.0158 under Average and Gaussian mixed noise compared with three quaternion-based restoration algorithms (QNLM, QNLTV, and quantization weighted nuclear norm minimization (QWNNM)).