bluuebunny/crossref_metadata_2025 huggingface dataset:
Pak1 pathway hyper-activation mediates resistance to endocrine therapy and CDK4/6 inhibitors in ER+ breast cancer
Authors: Belli Stefania , Esposito Daniela , Allotta Alessandra , Servetto Alberto , Ciciola Paola , Pesapane Ada , Ascione Claudia M. , Napolitano Fabiana , Di Mauro Concetta , Vigliar Elena , Iaccarino Antonino , De Angelis Carmine , Bianco Roberto , Formisano Luigi
Published: May 2023

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have been approved in combination with endocrine therapy (ET) to treat estrogen receptor-positive (ER+) metastatic breast cancer (BC). However, drug resistance represents the leading cause of breast cancer patients mortality. This study aimed to identify novel resistance mechanisms to ER antagonists in combination with CDK4/6 inhibitors. We generated two ER+ BC cell lines, T47D and MCF7, resistant to the combination of the ER antagonist fulvestrant and CDK4/6i abemaciclib, named T47D-FAR and MCF7-FAR. Transcriptomic analysis revealed common up-regulation of genes involved in MAPK and epithelial to mesenchymal transition (EMT) pathways in FAR cells, sustaining their hyper-invasive phenotype and increased anchorage-independent growth, compared to sensitive cells. FAR cells showed higher p21-activated kinase 1 (Pak1) expression and phosphorylation levels than parental cells. PAK1 knockdown by siRNAs hampered cell proliferation, reduced anchorage-independent growth and invasive properties of T47D-FAR and MCF7-FAR, re-sensitizing them to fulvestrant and abemaciclib. Conversely, over-expression of PAK1 in MCF7 and T47D cells increased tumor spheroids’ growth and invasion and reduced sensitivity to fulvestrant and abemaciclib, confirming its role in inducing drug resistance. Finally, treatment with Pak1 inhibitors, PF-3758309 (PF309) and NVS-PAK1-1, restored cell sensitivity to fulvestrant and abemaciclib of MCF7-FAR and T47D-FAR cells, both in vitro and in vivo. In conclusion, our data suggested a pivotal role for Pak1 in resistance to ET and CDK4/6i in ER+ breast cancers. These data might promote the rationale for the development of novel Pak1 inhibitors for treatment of patients with ER+ BC progressing on ET plus CDK4/6i.
An improved global vegetation health index dataset in detecting vegetation drought
Authors: Zeng Jingyu , Zhou Tao , Qu Yanping , Bento Virgílio A. , Qi Junyu , Xu Yixin , Li Ying , Wang Qianfeng
Published: May 2023

Due to global warming, drought events have become more frequent, which resulted in aggravated crop failures, food shortage, larger and more energetic wildfires, and have seriously affected socio-economic development and agricultural production. In this study, a global long-term (1981–2021), high-resolution (4 km) improved vegetation health index (VHI) dataset integrating climate, vegetation and soil moisture was developed. Based on drought records from the Emergency Event Database, we compared the detection efficiency of the VHI before and after its improvement in the occurrence and scope of observed drought events. The global drought detection efficiency of the improved high-resolution VHI dataset reached values as high as 85%, which is 14% higher than the original VHI dataset. The improved VHI dataset was also more sensitive to mild droughts and more accurate regarding the extent of droughts. This improved dataset can play an important role in long-term drought monitoring but also has the potential to assess the impact of drought on the agricultural, forestry, ecological and environmental sectors.
A novel beam stopper-based approach for scatter correction in digital planar radiography
Authors: Sakaltras N. , Pena A. , Martinez C. , Desco M. , Abella M.
Published: May 2023

X-ray scatter in planar radiography degrades the contrast resolution of the image, thus reducing its diagnostic utility. Antiscatter grids partially block scattered photons at the cost of increasing the dose delivered by two- to four-fold and posing geometrical restrictions that hinder their use for other acquisition settings, such as portable radiography. The few software-based approaches investigated for planar radiography mainly estimate the scatter map from a low-frequency version of the image. We present a novel method for scatter correction in planar imaging based on direct patient measurements. Samples from the shadowed regions of an additional partially obstructed projection acquired with a beam stopper placed between the X-ray source and the patient are used to estimate the scatter map. Evaluation with simulated and real data showed an increase in contrast resolution for both lung and spine and recovery of ground truth values superior to those of three recently proposed methods. Our method avoids the biases of post-processing methods and yields results similar to those for an antiscatter grid while removing geometrical restrictions at around half the radiation dose. It can be used in unconventional imaging techniques, such as portable radiography, where training datasets needed for deep-learning approaches would be very difficult to obtain.
Peripheral immune cell imbalance is associated with cortical beta-amyloid deposition and longitudinal cognitive decline
Authors: Mehta Neel H. , Zhou Liangdong , Li Yi , McIntire Laura Beth , Nordvig Anna , Butler Tracy , de Leon Mony , Chiang Gloria C.
Published: May 2023

Neuroinflammation is believed to be a key process in Alzheimer’s disease (AD) pathogenesis. Recently, the neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte ratios (LMR) have been proposed to be useful peripheral markers of inflammation. However, it is unclear how these inflammatory ratios relate to AD pathology, such as β-amyloid (Aβ) plaques and tau tangles. Using 18F-florbetapir and 18F-flortaucipir positron emission tomography (PET), we sought to determine how the NLR and LMR are associated with AD pathology both cross-sectionally and longitudinally. We further evaluated associations between the NLR and LMR and longitudinal cognitive decline. Using data from the Alzheimer’s Disease Neuroimaging Initiative, we analyzed blood, PET, and cognitive data from 1544 subjects—405 cognitively normal, 838 with mild cognitive impairment (MCI), and 301 with AD. Associations between the NLR and LMR and Aβ and tau on PET were assessed using ordinary least-squares and mixed-effects regression models, while adjusting for age, sex, years of education, and apolipoprotein E ε2 or ε4 carrier status. Associations between the NLR and LMR and cognitive function, as measured by the AD Assessment Scale-Cognitive Subscale, 13-item version, were also assessed. MCI and AD subjects had higher NLR (p = 0.017, p < 0.001, respectively) and lower LMR (p = 0.013, p = 0.023). The NLR, but not the LMR, was significantly associated with Aβ (p = 0.028), suggesting that higher NLR was associated with greater Aβ deposition in the brain. Neither the NLR nor the LMR was associated with tau deposition (p > 0.05). A higher NLR was associated with greater longitudinal cognitive decline (p < 0.001). A higher ratio of peripheral neutrophils to lymphocytes, possibly reflecting an imbalance in innate versus adaptive immunity, is related to greater Aβ deposition and longitudinal cognitive decline. As the field moves toward blood-based biomarkers of AD, the altered balance of innate versus adaptive immunity could be a useful biomarker of underlying pathology and may also serve as a potential therapeutic target.
A sustainable approach for the degradation kinetics study and stability assay of the SARS-CoV-2 oral antiviral drug Molnupiravir
Authors: Edrees Fadwa H. , Draz Mohammed E. , Saad Ahmed S. , Hammad Sherif F. , Mohamed Heba M.
Published: May 2023

Molnupiravir (MPV) is the first direct-acting oral antiviral drug that effectively decreases nasopharyngeal infections with SARS-CoV-2 virus. The stability of MPV was tested by subjecting the drug to various stress conditions. The drug is liable to oxidative, acidic, and alkaline degradation and showed significant stability against thermal degradation. Mass spectrometry identified the degradation products and guided suggestion of the degradation patterns. Interestingly, while inspecting the UV-absorption spectra, we observed no absorbance at 270 nm for the products of the three degradation pathways (c.f. intact MPV). Direct spectrophotometry seemed a solution that perfectly fit the purpose of the stability assay method in our case. It avoids sophisticated instrumentation and complex mathematical data manipulation. The method determined MPV accurately (100.32% ± 1.62) and selectively (99.49% ± 1.63) within the linear range of 1.50 × 10–5–4.0 × 10–4 M and down to a detection limit of 0.48 × 10–5 M. The proposed method is simple and does not require any preliminary separation or derivatization steps. The procedure proved its validity as per the ICH recommendations. The specificity was assessed in the presence of up to 90% degradation products. The study evaluated the greenness profile of the proposed analytical procedure using the National Environmental Methods Index (NEMI), the Analytical Eco-Scale, and the Green Analytical Procedure Index (GAPI). The three metrics unanimously agreed that the developed procedure results in a greener profile than the reported method. The method investigated the degradation reactions' kinetics and evaluated the reaction order, rate constant, and half-life time for each degradation process.
Dynamical analysis of an inverted pendulum with positive position feedback controller approximate uniform solution
Authors: Moatimid Galal M. , El-Sayed A. T. , Salman Hala F.
Published: May 2023

The inverted pendulum is controlled in this article by using the nonlinear control theory. From classical analytical mechanics, its substructure equation of motion is derived. Because of the inclusion of the restoring forces, the Taylor expansion is employed to facilitate the analysis. An estimated satisfactory periodic solution is obtained with the aid of the modified Homotopy perturbation method. A numerical technique based on the fourth-order Runge–Kutta method is employed to justify the previous solution. On the other hand, a positive position feedback control is developed to dampen the vibrations of an IP system subjected to multi-excitation forces. The multiple time scale perturbation technique of the second order is introduced as a mathematical method to solve a two-degree-of-freedom system that simulates the IP with the PPF at primary and 1:1 internal resonance. The stability of these solutions is checked with the aid of the Routh–Hurwitz criterion. A set of graphs, based on the frequency response equations resulting from the MSPT method, is incorporated. Additionally, a numerical simulation is set up with RK-4 to confirm the overall controlled performance of the studied model. The quality of the solution is confirmed by the match between the approximate solution and the numerical simulation. Numerous other nonlinear systems can be controlled using the provided control method. Illustrations are offered that pertain to implications in design and pedagogy. The linearized stability of IP near the fixed points as well as the phase portraits is depicted for the autonomous and non-autonomous cases. Because of the static stability of the IP, it is found that its instability can be suppressed by the increase of both the generalized force as well as the torsional constant stiffness of the spring. Additionally, the presence of the magnetic field enhances the stability of IP.
Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model
Authors: Rosmark Oskar , Kadefors Måns , Dellgren Göran , Karlsson Christofer , Ericsson Anders , Lindstedt Sandra , Malmström Johan , Hallgren Oskar , Larsson-Callerfelt Anna-Karin , Westergren-Thorsson Gunilla
Published: May 2023

Alveolar epithelial cells (AEC) have been implicated in pathological remodelling. We examined the capacity of AEC to produce extracellular matrix (ECM) and thereby directly contribute towards remodelling in chronic lung diseases. Cryopreserved type 2 AEC (AEC2) from healthy lungs and chronic obstructive pulmonary disease (COPD) afflicted lungs were cultured in decellularized healthy human lung slices for 13 days. Healthy-derived AEC2 were treated with transforming growth factor ß1 (TGF-β1) to evaluate the plasticity of their ECM production. Evaluation of phenotypic markers and expression of matrisome genes and proteins were evaluated by RNA-sequencing, mass spectrometry and immunohistochemistry. The AEC2 displayed an AEC marker profile similar to freshly isolated AEC2 throughout the 13-day culture period. COPD-derived AECs proliferated as healthy AECs with few differences in gene and protein expression while retaining increased expression of disease marker HLA-A. The AEC2 expressed basement membrane components and a complex set of interstitial ECM proteins. TGF-β1 stimuli induced a significant change in interstitial ECM production from AEC2 without loss of specific AEC marker expression. This study reveals a previously unexplored potential of AEC to directly contribute to ECM turnover by producing interstitial ECM proteins, motivating a re-evaluation of the role of AEC2 in pathological lung remodelling.
Adaptive elevator kinematics optimization based dual response algorithm for determining proper levels in plaster milling process parameters
Authors: Luangpaiboon Pongchanun , Juttijudata Sirirat
Published: May 2023

This study proposes a novel hybrid approach, called Adaptive/Elevator Kinematics Optimization algorithm based on dual response algorithm (A/EKO-DRA), to enhance the robust parameters estimation and design of the plaster milling process. The A/EKO-DRA method reduces variability while maintaining the desired output target, thereby minimizing the impact of variance on the expected stucco combined water. The performance of the A/EKO-DRA is compared with conventional processes through numerical examples and simulations. The results show that the A/EKO-DRA method has the lowest mean absolute errors among other methods in terms of parameter estimation, and it achieves the response mean of 5.927 percent, which meets the target value of 5.9 percent for industrial enclosures, with much reduction in the response variance. Overall, the A/EKO-DRA method is a promising approach for optimizing the plaster milling process parameters.
Construction of an oxidative stress-related lncRNAs signature to predict prognosis and the immune response in gastric cancer
Authors: Zhang Hui , Feng Huawei , Yu Tiansong , Zhang Man , Liu Zhikui , Ma Lidan , Liu Hongsheng
Published: May 2023

Oxidative stress, as a characteristic of cellular aerobic metabolism, plays a crucial regulatory role in the development and metastasis of gastric cancer (GC). Long noncoding RNAs (lncRNAs) are important regulators in GC development. However, research on the prognostic patterns of oxidative stress-related lncRNAs (OSRLs) and their functions in the immune microenvironment is currently insufficient. We identified the OSRLs signature (DIP2A-IT1, DUXAP8, TP53TG1, SNHG5, AC091057.1, AL355001.1, ARRDC1-AS1, and COLCA1) from 185 oxidative stress-related genes in The Cancer Genome Atlas (TCGA) cohort via random survival forest and Cox analyses, and the results were subsequently validated in the Gene Expression Omnibus (GEO) dataset. The patients were divided into high- and low-risk groups by the risk score of the OSRLs signature. Longer overall survival was detected in the low-risk group than in the high-risk group in both the TCGA cohort (P < 0. 001, HR = 0.43, 95% CI 0.31–0.62) and the GEO cohort (P = 0.014, HR = 0.67, 95% CI 0.48–0.93). Next, multivariate Cox analysis identified that the risk model was an independent prognostic characteristic (HR > 1, P = 0.005), and time-dependent receiver operating characteristic (ROC) curve analysis and nomogram analysis were utilized to evaluate the predictive ability of the risk model. Next, gene set enrichment analysis revealed that the immune-related pathway, Wnt/$$\upbeta$$
β
-catenin signature, mammalian target of rapamycin complex 1 signature, and cytokine‒cytokine receptor interaction was enriched. High-risk patients were more responsive to CD200, TNFSF4, TNFSF9, and BTNL2 immune checkpoint blockade. The results of qRT‒PCR further proved the accuracy of our bioinformatic analysis. Overall, our study identified a novel OSRLs signature that can serve as a promising biomarker and prognostic indicator, which provides a personalized predictive approach for patient prognosis evaluation and treatment.
Improved measurement method for roadbed bearing capacity based on PFWD dynamic modulus control
Authors: Li Danfeng , Zhang Zhuojie , Zhang Guangming
Published: May 2023

To address current challenges of difficult standardisation of dynamic determination of roadbed bearing capacity and excessive deviations in deflection control, this paper proposes a improved measurement method for roadbed load-bearing capacity based on the dynamic modulus control using a portable falling weight deflectometer (PFWD). The detection range of PFWD is determined by theoretical analysis. Based on the range, a finite element numerical model was developed, the spatial distribution and attenuation of the dynamic stress of the roadbed soil in the depth and horizontal directions are determined. The variation of the vertical dynamic stress with depth is not characterized by a gradual decrease, as is commonly believed, but rather by an increase followed by a decrease. The underlying reasons for the difference between static and dynamic indicators are explored. Using the improved method, a prediction model with dynamic bending as the detection index and static rebound modulus as the control index was developed. The proposed model can improve precision accuracy as well as detection efficiency, verify the effectiveness of the improved method, which is important for accurate dynamic measurement and evaluation of highway roadbed bearing capacity.
Phase transitions in the classical simulability of open quantum systems
Authors: Azad F. , Hallam A. , Morley J. , Green A. G.
Published: May 2023

We introduce a Langevin unravelling of the density matrix evolution of an open quantum system over matrix product states, which we term the time-dependent variational principle-Langevin equation. This allows the study of entanglement dynamics as a function of both temperature and coupling to the environment. As the strength of coupling to and temperature of the environment is increased, we find a transition where the entanglement of the individual trajectories saturates, permitting a classical simulation of the system for all times. This is the Hamiltonian open system counterpart of the saturation in entanglement found in random circuits with projective or weak measurements. If a system is open, there is a limit to the advantage in simulating its behaviour on a quantum computer, even when that evolution harbours important quantum effects. Moreover, if a quantum simulator is in this phase, it cannot simulate with quantum advantage.
Bulk and single-cell transcriptome profiling reveal the metabolic heterogeneity in gastric cancer
Authors: Tao Guoqiang , Wen Xiangyu , Wang Xingxing , Zhou Qi
Published: May 2023

Metabolic reprogramming has been defined as a key hall mark of human tumors. However, metabolic heterogeneity in gastric cancer has not been elucidated. Here we separated the TCGA-STAD dataset into two metabolic subtypes. The differences between subtypes were elaborated in terms of transcriptomics, genomics, tumor-infiltrating cells, and single-cell resolution. We found that metabolic subtype 1 is predominantly characterized by low metabolism, high immune cell infiltration. Subtype 2 is mainly characterized by high metabolism and low immune cell infiltration. From single-cell resolution, we found that the high metabolism of subtype 2 is dominated by epithelial cells. Not only epithelial cells, but also various immune cells and stromal cells showed high metabolism in subtype 2 and low metabolism in subtype 1. Our study established a classification of gastric cancer metabolic subtypes and explored the differences between subtypes from multiple dimensions, especially the single-cell resolution.
Engineering nanowires in bacteria to elucidate electron transport structural–functional relationships
Authors: Myers Ben , Catrambone Francesco , Allen Stephanie , Hill Phil J. , Kovacs Katalin , Rawson Frankie J.
Published: May 2023

Bacterial pilin nanowires are protein complexes, suggested to possess electroactive capabilities forming part of the cells’ bioenergetic programming. Their role is thought to be linked to facilitating electron transfer between cells and the external environment to permit metabolism and cell-to-cell communication. There is a significant debate, with varying hypotheses as to the nature of the proteins currently lying between type-IV pilin-based nanowires and polymerised cytochrome-based filaments. Importantly, to date, there is a very limited structure–function analysis of these structures within whole bacteria. In this work, we engineered Cupriavidus necator H16, a model autotrophic organism to express differing aromatic modifications of type-IV pilus proteins to establish structure–function relationships on conductivity and the effects this has on pili structure. This was achieved via a combination of high-resolution PeakForce tunnelling atomic force microscopy (PeakForce TUNA™) technology, alongside conventional electrochemical approaches enabling the elucidation of conductive nanowires emanating from whole bacterial cells. This work is the first example of functional type-IV pili protein nanowires produced under aerobic conditions using a Cupriavidus necator chassis. This work has far-reaching consequences in understanding the basis of bio-electrical communication between cells and with their external environment.
Termination of trastuzumab in HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression
Authors: Dogan Izzet , Aydin Esra , Khanmammadov Nijat , Paksoy Nail , Saip Pinar , Aydiner Adnan
Published: May 2023

The purpose of the study was to assess the prognosis of HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression and investigate the predictors of complete response. HER2-positive metastatic breast cancer patients who received long-term trastuzumab were included in the study. Predictors of complete response were analyzed with binary regression analysis. The prognosis of patients who had their trastuzumab-based treatment terminated was assessed. Eighty patients were involved in the study. The patients were received with trastuzumab for a median of 62 months (12–191). A complete response was observed in 60 (75%) patients. The median duration to development of complete response was found as 14.8 months (2.4–55). In logistic regression analysis: using endocrine therapy with trastuzumab (p = 0.04), menopausal status (p = 0.03), and the number of metastatic sites (p = 0.01) were found to be statistically significant factors for a complete response. Trastuzumab-based therapy of fifteen patients was terminated, six (40%) patients continued to receive an aromatase inhibitor, and nine (60%) patients were followed up without treatment. After termination of trastuzumab, at a median follow-up of 32 months (11–66), recurrence was detected in two (13.3%) patients. We detected that menopausal status, the number of metastatic sites, and using endocrine therapy with trastuzumab were predictors of complete response in HER2-positive metastatic breast cancer patients who received long-term trastuzumab-based therapy. We observed that HER2-positive metastatic breast cancer patients may be completely cured with trastuzumab-based therapy. There are no defined criteria for termination of trastuzumab treatment in this selected patient group. It is necessary to confirm our data with multicenter studies involving a large number of patients.
Physical fitness of primary school children differs depending on their timing of school enrollment
Authors: Teich Paula , Fühner Thea , Granacher Urs , Kliegl Reinhold
Published: May 2023

Previous research has shown that children who were enrolled to school according to the legal key date (i.e., keyage children, between eight and nine years in third grade) exhibited a linear physical fitness development in the ninth year of life. In contrast, children who were enrolled with a delay (i.e., older-than-keyage children [OTK], between nine and ten years in third grade) exhibited a lower physical fitness compared to what would be expected for their age. In these studies, cross-sectional age differences within third grade and timing of school enrollment were confounded. The present study investigated the longitudinal development of keyage and OTK children from third to fifth grade. This design also afforded a comparison of the two groups at the same average chronological age, that is a dissociation of the effects of timing of school enrollment and age. We tested six physical fitness components: cardiorespiratory endurance, coordination, speed, power of lower and upper limbs, and static balance. 1502 children (i.e., 1206 keyage and 296 OTK children) from 35 schools were tested in third, fourth, and fifth grade. Except for cardiorespiratory endurance, both groups developed from third to fourth and from fourth to fifth grade and keyage children outperformed OTK children at the average ages of 9.5 or 10.5 years. For cardiorespiratory endurance, there was no significant gain from fourth to fifth grade and keyage and OTK children did not differ significantly at 10.5 years of age. One reason for a delayed school enrollment could be that a child is (or is perceived as) biologically younger than their chronological age at the school entry examination, implying a negative correlation between chronological and biological age for OTK children. Indeed, a simple reflection of chronological age brought the developmental rate of the chronologically youngest OTK children in line with the developmental rate observed for keyage children, but did not eliminate all differences. The mapping of chronological and biological age of OTK children and other possible reasons for lower physical fitness of OTK children remain a task for future research.
Extended depth of field in augmented reality
Authors: Kim Sung Kyu , Kwon Yongjoon , Yoon Ki-Hyuk
Published: May 2023

The 3D display device shows an image with depth information. Conventional 3D display devices based on binocular parallax can focus accurately only on the depth of a specific screen. Because the human eye has a narrow depth of field (DOF) under normal circumstances, 3D displays that provide a relatively wide range of virtual depth areas have limitations on the DOF where clear 3D images are seen. To resolve this problem, it is necessary to find the optical conditions to extend the DOF and analyze the phenomena related to it. For this, by using the Rayleigh criterion and the Strehl ratio, a criterion for this extension of the DOF is suggested. A practical optical structure that can effectively extend the DOF is devised using a flat panel display. This optical structure could be applied to AR, VR, and MR in the field of near-eye displays. From the results of this research, the fundamental optical conditions and standards are proposed for 3D displays that will provide 3D images with extended DOF in the future. Furthermore, it is also expected that these conditions and criteria can be applied to optical designs for the required performance in the development of 3D displays in various fields.
Selection and validation of reference genes for RT-qPCR normalization of porcine alveolar macrophages (PAMs) for PRRSV studies
Authors: Oh Dayoung , De Spiegelaere Ward , Nauwynck Hans J.
Published: May 2023

Porcine alveolar macrophages (PAMs) are widely used for in vitro studies of porcine respiratory viruses. Gene expression in these cells is altered by viral infection and cellular immune response. Real-time reverse transcription polymerase chain reaction (RT-qPCR) is a powerful technique for analyzing these changes. In order to obtain reliable quantitative RT-qPCR data and come to sound conclusions, stable reference genes are needed for normalization of target gene expression. In the present study, we evaluated the expression stability of nine reference genes in PAMs during cultivation and upon porcine reproductive and respiratory syndrome virus (PRRSV) inoculation. Using geNorm and NormFinder algorithms, we identified PSAP and GAPDH as the most stable reference genes under all experimental conditions. The selected reference genes were used for the normalization of CD163 expression under different conditions. This study demonstrates that selection of appropriate reference genes is essential for normalization and validation of RT-qPCR data across all experimental conditions. This study provides a new set of stable reference genes for future studies with porcine respiratory viruses in PAMs.
Ensemble heterogeneity mimics ageing for endosomal dynamics within eukaryotic cells
Authors: Korabel Nickolay , Taloni Alessandro , Pagnini Gianni , Allan Viki , Fedotov Sergei , Waigh Thomas Andrew
Published: May 2023

Transport processes of many structures inside living cells display anomalous diffusion, such as endosomes in eukaryotic cells. They are also heterogeneous in space and time. Large ensembles of single particle trajectories allow the heterogeneities to be quantified in detail and provide insights for mathematical modelling. The development of accurate mathematical models for heterogeneous dynamics has the potential to enable the design and optimization of various technological applications, for example, the design of effective drug delivery systems. Central questions in the analysis of anomalous dynamics are ergodicity and statistical ageing which allow for selecting the proper model for the description. It is believed that non-ergodicity and ageing occur concurrently. However, we found that the anomalous dynamics of endosomes is paradoxical since it is ergodic but shows ageing. We show that this behaviour is caused by ensemble heterogeneity that, in addition to space-time heterogeneity within a single trajectory, is an inherent property of endosomal motion. Our work introduces novel approaches for the analysis and modelling of heterogeneous dynamics.
Effects of normal aging on the mouse retina assessed by full-field flash and flicker electroretinography
Authors: Park Jason C. , Persidina Oksana , Balasubramanian Giri , Nguyen Tara , Pradeep Anubhav , Hetling John R. , McAnany J. Jason
Published: May 2023

Changes in the full-field flash and flicker electroretinogram (ERG) that accompany normal aging were evaluated in mice. ERGs were recorded from a single cohort of C57BL/6J mice from 5 to 70 weeks of age using conventional techniques. Dark-adapted ERGs were recorded for flash luminances of − 3.0 to 1.5 log cd-s-m−2; a- and b-wave amplitude and implicit time (IT) were calculated from these responses. In addition, light-adapted flicker ERGs elicited by sinusoidally modulated light were measured for temporal frequencies of 2 to 31 Hz. Amplitudes and phases were extracted from the flicker responses using Fourier analysis. Linear quantile mixed models were used for statistical comparisons of the effects of age on amplitude and timing. There was a significant decrease in a-wave amplitude (p < 0.001) and b-wave amplitude (p < 0.001) over the 65 week study. From 5 to 70 weeks, the a- and b-wave amplitudes decreased by a factor of approximately 2. There was a small (2–14 ms), but significant (p < 0.001), delay in a- and b-wave IT over the 65 week study. There was also a significant decrease in fundamental amplitude (factor of 1.8, p < 0.001) and second harmonic amplitude (factor of 1.5, p < 0.001) over time. There were no significant age-related effects on the phase of these components (both p > 0.06). These results indicate that age scales the single flash and flicker ERG similarly, reducing response amplitude by a factor of approximately 2, from 5 to 70 weeks, with small or no effect on response timing. These data may be useful for guiding future longitudinal pre-clinical therapeutic studies.
Comparative genome features and secondary metabolite biosynthetic potential of Kutzneria chonburiensis and other species of the genus Kutzneria
Authors: Chanama Manee , Prombutara Pinidphon , Chanama Suchart
Published: May 2023

Actinobacteria are well known as a rich source of diversity of bioactive secondary metabolites.Kutzneria, a rare actinobacteria belonging to the familyPseudonocardiaceaehas abundance of secondary metabolite biosynthetic gene clusters (BGCs) and is one of important source of natural products and worthy of priority investigation. Currently,Kutzneria chonburiensisSMC256Thas been the latest type-strain of the genus and its genome sequence has not been reported yet. Therefore, we present the first report of new complete genome sequence of SMC256T(genome size of 10.4 Mbp) with genome annotation and feature comparison between SMC256Tand other publicly availableKutzneriaspecies. The results from comparative and functional genomic analyses regarding the phylogenomic and the clusters of orthologous groups of proteins (COGs) analyses indicated that SMC256Tis most closely related toKutzneriasp. 744,Kutzneria kofuensis, Kutzneriasp. CA-103260 andKutzneria buriramensis. Furthermore, a total of 322 BGCs were also detected and showed diversity among theKutzneriagenomes. Out of which, 38 clusters showing the best hit to the most known BGCs were predicted in the SMC256Tgenome. We observed that six clusters responsible for biosynthesis of antimicrobials/antitumor metabolites were strain-specific inKutzneria chonburiensis. These putative metabolites include virginiamycin S1, lysolipin I, esmeraldin, rakicidin, aclacinomycin and streptoseomycin. Based on these findings, the genome ofKutzneria chonburiensiscontains distinct and unidentified BGCs different from other members of the genus, and the use of integrative genomic-based approach would be a useful alternative effort to target, isolate and identify putative and undiscovered secondary metabolites suspected to have new and/or specific bioactivity in theKutzneria.
Effects of three microtubule-associated proteins (MAP2, MAP4, and Tau) on microtubules’ physical properties and neurite morphology
Authors: Nishida Kohei , Matsumura Kosuke , Tamura Miki , Nakamichi Takuto , Shimamori Keiya , Kuragano Masahiro , Kabir Arif Md. Rashedul , Kakugo Akira , Kotani Susumu , Nishishita Naoki , Tokuraku Kiyotaka
Published: May 2023

The physical properties of cytoskeletal microtubules have a multifaceted effect on the expression of their cellular functions. A superfamily of microtubule-associated proteins, MAP2, MAP4, and tau, promote the polymerization of microtubules, stabilize the formed microtubules, and affect the physical properties of microtubules. Here, we show differences in the effects of these three MAPs on the physical properties of microtubules. When microtubule-binding domain fragments of MAP2, tau, and three MAP4 isoforms were added to microtubules in vitro and observed by fluorescence microscopy, tau-bound microtubules showed a straighter morphology than the microtubules bound by MAP2 and the three MAP4 isoforms. Flexural rigidity was evaluated by the shape of the teardrop pattern formed when microtubules were placed in a hydrodynamic flow, revealing that tau-bound microtubules were the least flexible. When full-length MAPs fused with EGFP were expressed in human neuroblastoma (SH-SY5Y) cells, the microtubules in apical regions of protrusions expressing tau were straighter than in cells expressing MAP2 and MAP4. On the other hand, the protrusions of tau-expressing cells had the fewest branches. These results suggest that the properties of microtubules, which are regulated by MAPs, contribute to the morphogenesis of neurites.
Portable, high speed blood flow measurements enabled by long wavelength, interferometric diffuse correlation spectroscopy (LW-iDCS)
Authors: Robinson Mitchell B. , Renna Marco , Ozana Nisan , Martin Alyssa N. , Otic Nikola , Carp Stefan A. , Franceschini Maria Angela
Published: May 2023

Diffuse correlation spectroscopy (DCS) is an optical technique that can be used to characterize blood flow in tissue. The measurement of cerebral hemodynamics has arisen as a promising use case for DCS, though traditional implementations of DCS exhibit suboptimal signal-to-noise ratio (SNR) and cerebral sensitivity to make robust measurements of cerebral blood flow in adults. In this work, we present long wavelength, interferometric DCS (LW-iDCS), which combines the use of a longer illumination wavelength (1064 nm), multi-speckle, and interferometric detection, to improve both cerebral sensitivity and SNR. Through direct comparison with long wavelength DCS based on superconducting nanowire single photon detectors, we demonstrate an approximate 5× improvement in SNR over a single channel of LW-DCS in the measured blood flow signals in human subjects. We show equivalence of extracted blood flow between LW-DCS and LW-iDCS, and demonstrate the feasibility of LW-iDCS measured at 100 Hz at a source-detector separation of 3.5 cm. This improvement in performance has the potential to enable robust measurement of cerebral hemodynamics and unlock novel use cases for diffuse correlation spectroscopy.
Estimating urban spatial structure based on remote sensing data
Authors: Kii Masanobu , Tamaki Tetsuya , Suzuki Tatsuya , Nonomura Atsuko
Published: May 2023

Understanding the spatial structure of a city is essential for formulating a spatial strategy for that city. In this study, we propose a method for analyzing the functional spatial structure of cities based on satellite remote sensing data. In this method, we first assume that urban functions consist of residential and central functions, and that these functions are measured by trip attraction by purpose. Next, we develop a model to explain trip attraction using remote sensing data, and estimate trip attraction on a grid basis. Using the estimated trip attraction, we created a contour tree to identify the spatial extent of the city and the hierarchical structure of the central functions of the city. As a result of applying this method to the Tokyo metropolitan area, we found that (1) our method reproduced 84% of urban areas and 94% of non-urban areas defined by the government, (2) our method extracted 848 urban centers, and their size distribution followed a Pareto distribution, and (3) the top-ranking urban centers were consistent with the districts defined in the master plans for the metropolitan area. Based on the results, we discussed the applicability of our method to urban structure analysis.
Individual-specific functional connectivity improves prediction of Alzheimer’s disease’s symptoms in elderly people regardless of APOE ε4 genotype
Authors: Hua Lin , Gao Fei , Xia Xiaoluan , Guo Qiwei , Zhao Yonghua , Huang Shaohui , Yuan Zhen
Published: May 2023

To date, reliable biomarkers remain unclear that could link functional connectivity to patients’ symptoms for detecting and predicting the process from normal aging to Alzheimer’s disease (AD) in elderly people with specific genotypes. To address this, individual-specific functional connectivity is constructed for elderly participants with/without APOE ε4 allele. Then, we utilize recursive feature selection-based machine learning to reveal individual brain-behavior relationships and to predict the symptom transition in different genotypes. Our findings reveal that compared with conventional atlas-based functional connectivity, individual-specific functional connectivity exhibits higher classification and prediction performance from normal aging to AD in both APOE ε4 groups, while no significant performance is detected when the data of two genotyping groups are combined. Furthermore, individual-specific between-network connectivity constitutes a major contributor to assessing cognitive symptoms. This study highlights the essential role of individual variation in cortical functional anatomy and the integration of brain and behavior in predicting individualized symptoms.
The utility of historical records for hazard analysis in an area of marginal cyclone influence
Authors: Switzer Adam D. , Christensen Joseph , Aldridge Joanna , Taylor David , Churchill Jim , Watson Holly , Fraser Matthew W. , Shaw Jenny
Published: May 2023

Shark Bay Marine Park is a UNESCO World Heritage Property located in a region of marginal tropical cyclone influence. Sustainable management of this unique environment as the climate changes requires a quantified understanding of its vulnerability to natural hazards. Here, we outline a structured analysis of novel historical archive information that has uncovered reports of an extreme storm surge associated with a Tropical Cyclone in 1921 that generated remarkable overland flow which left fish and sharks stranded up to 9.66 km (6 miles) inland. Weighted information from historical archives is placed in a new framework and provide inputs to modelling of this event which improves the understanding of its magnitude and furnishes records of the impacts of what occurred on that day and notably also in the years following. The suite of plausible tracks that reproduce the historical data contextualise the storm as a marginal Category 4 or 5 storm and its return interval as equivalent or slightly greater than the current local planning level for coastal flooding in the region. The outcome underscores the global importance of examining the probable maximum event for risk management in areas of marginal cyclone influence where vulnerable ecosystems or vital regional infrastructure of key economic importance are located, and the need to factor in TC risk in marine conservation and planning in the Shark Bay World Heritage Property.
Artistic representations of data can help bridge the US political divide over climate change
Authors: Li Nan , Villanueva Isabel I. , Jilk Thomas , Van Matre Brianna Rae , Brossard Dominique
Published: May 2023

Visual art has been used to revamp the portrayal of climate change with the aims of engaging emotions and expanding nonexperts’ psychological capacity to perceive its relevance. However, empirical evidence supporting the effectiveness of artistic representation of data as a tool for public communication is lacking. Using controlled experiments with two national samples of U.S. adults (total N = 671), here we found that artistic visualizations elicited stronger positive emotions than informationally equivalent data graphs but did not differ in their perceived credibility or effectiveness as visual aids for learning. When used to prompt individual reflection, artistic visualizations appeared to mitigate the political division in viewers’ perceived relevance of climate change that could otherwise be exacerbated by exposure to data graphs.
Exposure to and learning from the IPCC special report on 1.5 °C global warming, and public support for climate protests and mitigation policies
Authors: Doran Rouven , Ogunbode Charles A. , Böhm Gisela , Gregersen Thea
Published: May 2023

Based on national survey data from Norway, this study assesses if exposure to the IPCC special report on global warming of 1.5 °C can be associated with support for climate protests and mitigation policies. Respondents were asked if they had heard about the report (closed-ended question) and what they had learned from or about the report (open-ended question). Analyses of the closed-ended question showed that those who had heard about the report were also more likely to express their support for, as well as to plan on engaging in, protest for increased action by the government against climate change. A similar pattern was observed with respect to support for policy changes that can assist in mitigating climate change. Complementary analyses of the open-ended question revealed that evaluative statements formed the largest category of responses. This category included both references to the seriousness of the evolving climate crisis and comments questioning the credibility of the presented information, with the former being the most frequent response. The findings from this study are discussed in the context of public engagement with climate change, with a particular scope on the potential impacts of making the insights from scientific reports known to the general public.
Macro-microporous ZIF-8 MOF complexed with lysosomal pH-adjusting hexadecylsulfonylfluoride as tumor vaccine delivery systems for improving anti-tumor cellular immunity
Authors: Zuo Qinhua , Li Tiantian , Huang Linghong , Liu Zonghua , Xue Wei
Published: May 2023

Schematic Illustration of the Preparation of SOM-ZIF-8-based Antigen Delivery System and Its Role in Enhancing Antigen Cross-presentation and Cellular Immunity for Cancer Immunotherapy.
Fabricating penta-coordinated Fe single atoms for electrochemical CO2reduction to syngas
Authors: Wang Linjie , Lai Xiaofei , Xu Yafeng , Luo Shaojuan , Wang Lu , Yan Kai , Zhang Da , Feng Sitong , Xu Yong
Published: May 2023

Syngas with a tunable H2/CO ratio can be producedviaelectrocatalytic CO2reduction over a penta-coordinated Fe single atom catalyst.
Machine learning reaction barriers in low data regimes: a horizontal and diagonal transfer learning approach
Authors: Espley Samuel G. , Farrar Elliot H. E. , Buttar David , Tomasi Simone , Grayson Matthew N.
Published: May 2023

Transfer learning (TL) is used to adapt existing neural networks to provide reaction barrier predictions for different reaction classes (horizontal TL) at higher levels of theory (diagonal TL) with tens of datapoints.
Catalytic activation of remote alkenes through silyl-rhodium(iii) complexes
Authors: Prieto-Pascual Unai , Martínez de Morentin Aitor , Choquesillo-Lazarte Duane , Rodríguez-Diéguez Antonio , Freixa Zoraida , Huertos Miguel A.
Published: May 2023

Rhodium(iii) complexes, bearing silyl-nitrogen ligands, as catalysts for the tandem isomerization–hydrosilylation reaction.
Triazole-induced planarization of a twisted tetrazole-based molecule towards energetic materials with improved thermostability and insensitivity
Authors: Yin Zhaoyang , Hu Lijincao , Huang Wei , Liu Yuji , Tang Yongxing
Published: May 2023

Incorporation of a triazole ring into a twisted tetrazole-based energetic molecule achieves structural planarization, accompanied by an increase in thermal stability and a decrease in mechanical sensitivity.
Wet spinning imogolite nanotube fibres: an in situ process study
Authors: Moore Joseph F. , Paineau Erwan , Launois Pascale , Shaffer Milo S. P.
Published: May 2023

In situ polarised optical microscopy, during coagulation spinning and washing, reveals the competing processes determining the mechanical properties of pure imogolite nanotube fibres.
N-2,2,2-Trifluoroethylisatin ketimine as a 1,2-dipolarophile for [3 + 2]-addition to access optically pure spirothiazolidine oxindoles
Authors: Prasad Madavi S. , Bharani Sankar , Sivaprakash Murugesan , Vadivelu Prabha , Kumar Durairajan Siva Sundara , Chowhan L. Raju
Published: May 2023

The first asymmetric synthesis of N-2,2,2-trifluoroethylspirothiazolidine oxindoles is presented where N-2,2,2-trifluoroethylisatin ketimine is employed as a 1,2-dipolarophile for the first time in a [3 + 2]-addition reaction.
Retraction: Direct Sb–S cross-coupling of halostibines with thiols and disulfides at room temperature
Authors: Li Wei , Li Shan , Wang Zixiu , Liu Chenfu , Ye Yifei , Chen Yujing , Xiong Yuyan , Lei Jian
Published: May 2023

Retraction of ‘Direct Sb–S cross-coupling of halostibines with thiols and disulfides at room temperature’ by Wei Li et al., Org. Biomol. Chem., 2021, Accepted Manuscript, https://doi.org/10.1039/d1ob00959a.
Anion-exchange facilitated selective extraction of sulfate and phosphate by overcoming the Hofmeister bias
Authors: Gogoi Anamika , Dutta Dipjyoti , Gil-Hernández Beatriz , Dey Sandeep Kumar
Published: May 2023

The paper showcases the anion recognition approach for the selective and efficient extraction of sulfate and phosphates by nitrophenyl-functionalized tris-urea and thiourea receptors, respectively from highly competitive aqueous media.