bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulations on multiple tropical cyclones event associated with monsoon trough over the western North Pacific
Authors: Huang Qijun , Guo Bingyao , Ge Xuyang 
Published: November 2022

AbstractIn this study, the formation of an idealized multiple tropical cyclones (MTCs) event within a monsoon trough (MT) region is investigated by using the weather forecasting model (WRF_ARW). Sensitivity experiments are conducted by specifying different initial conditions. It is revealed that both dynamical and thermodynamical conditions associated with the MT are important in triggering MTCs event over the western North Pacific basin. In the composite active years, which have a strong MT with higher ambient moisture, an MTCs event is produced. In contrast, no MTCs event occurs in the inactive years, which confirms the previous observational study. The possible pathway for the formation of MTCs event is proposed. In the active years, under favourable moist environments, the first TC is generated faster through the greater barotropic kinetic energy conversion. Once the first tropical cyclone (TC) is generated, the energy dispersion induced low‐level Rossby wave train acts as a precursor to the second TC. Furthermore, the upper‐level asymmetric outflow jet acts as a dynamical forcing to induce vertical motion, which builds up a favourable environmental condition for a second TC development. This work provides some insights into the formation of MTCs event.
Elevated plasma miR‐210 expression is associated with atypical genitalia in patients with 46,XY differences in sex development
Authors: Elias Felipe Martins , Nishi Mirian Yumi , Sircili Maria Helena Palma , Bastista Rafael Loch , Gomes Nathalia Lisboa , Ferrari Maria Tereza Martins , Costa Elaine Maria Frade , Denes Francisco Tibor , Mendonca Berenice Bilharinho , Domenice Sorahia 
Published: November 2022

AbstractBackgroundDifferences of sex development (DSD) is a term used for conditions in which the chromosomal, gonadal or phenotypical sex is atypical. 46,XY DSD patients frequently present undervirilized external genitalia. The expression of different miRNAs in many organs of the male genital system has been reported, and these miRNAs have been associated with testicular function and its disorders, but no description has been related to DSD conditions. This study aimed to evaluate the plasma expression of miR‐210 in 46,XY DSD patients who presented atypical genitalia at birth.MethodsEighteen 46,XY DSD patients who presented atypical genitalia (undescended testis and/or hypospadias, bifid scrotum or micropenis) at birth and 36 male control individuals were selected. Plasma levels of miR‐210 and reference miR‐23a were measured using RT‐qPCR and the data were analysed by the 2−ΔCt method.ResultsMiR‐210 plasma levels were significantly higher in 46,XY DSD patients with atypical genitalia than in male control subjects (p = 0.0024). A positive association between miR‐210 levels and the presence of cryptorchidism and hypospadias (p = 0.0146 and p = 0.0223) was found in these patients. Significantly higher levels of miR‐210 were observed in patients with 46,XY DSD and cryptorchidism than in control subjects (p = 0.0118). These results are in agreement with previous literature reports, in which increased levels of miR‐210 expression were observed in human testicular tissue from adult males with undescended testes in comparison with samples of descended testes.ConclusionOur study showed a positive association between the presence of atypical genitalia and plasma levels of miR‐210 expression in the group of patients with 46,XY DSD of unknown aetiology studied. These findings contribute to reveal a new perspective on the role of miRNAs in the development of male external genitalia and the broad spectrum of phenotypes presented by patients with 46,XY DSD.
The compound heterozygous mutations of c.607G>a and c.657delC in the FAH gene are associated with renal damage with hereditary tyrosinemia type 1 (HT1)
Authors: Chi Huan , Gan Chun , Jiang Yaru , Chen Dan , Qiu Jiawen , Yang Qing , Chen Yaxi , Wang Mo , Yang Haiping , Jiang Wei , Li Qiu 
Published: November 2022

AbstractBackgroundHereditary tyrosinemia type 1 (HT1) is a rare inherited metabolic disease characterized by severe liver and renal dysfunction. Early identification in affected children is critical for improved treatment options and prognosis.MethodsIn this study, we identified novel compound heterozygous mutations (NM_000137: c.657delC (p.K220Rfs*12) and c.607G>A (p.A203T)) in the fumarylacetoacetate hydrolase (FAH) gene in a family. We also characterized the clinical phenotype of the proband and verified the pathogenic effects of the mutations. Furthermore, we explored the pathogenic mechanism of renal injury through renal biopsy pathology and cell‐based in vitro assays. Our study aims to verify the association between novel fumarylacetoacetate hydrolase (FAH) variants and HT1, confirm the pathogenic effects of the mutations and explore the pathogenic mechanism of renal injury.ResultsWe showed these FAH mutations were inherited in an autosomal recessive manner and resulted in abnormal FAH protein expression and dysfunction, leading to fumarylacetoacetate (FAA) accumulation. The proband also showed apparent renal injury, including glomerular filtration barrier dysfunction and abnormal tubular protein reabsorption.ConclusionsThese observations may provide deeper insights on disease pathogenesis and identify potential therapeutic approaches for HT1 from a genetic perspective. Similarly, we hope to provide valuable information for genetic counseling and prenatal diagnostics.
Study on the thermal and mechanical properties of two‐dimensional d‐Ti3C2Tx filled polyamide 66 nanocomposite
Authors: Li Haonan , Wang Libo , Xu Shuya , Li Han , Dai Yahui , Zhou Aiguo 
Published: November 2022

AbstractTwo‐dimensional (2D) transition‐metal carbides, nitrides, and carbonitrides exhibit excellent thermal, mechanical, and electrical properties, and MXene displays good advantages in improving the mechanical properties of composites. In this study, the injection molding method is employed to introduce d‐Ti3C2Tx MXene into the polyamide 66 matrix, yielding a d‐Ti3C2Tx/PA66 nanocomposite. The tensile strength, flexural strength, Young's modulus, and hardness of d‐Ti3C2Tx/PA66 nanocomposites are higher than that of pure PA66, owing to the high strength of the d‐Ti3C2Tx nanosheets, good interfacial bonding, and stress transfer between the PA66 matrix and d‐Ti3C2Tx nanofiller. TGA and DMA results revealed that the addition of d‐Ti3C2Tx into the PA66 matrix improves the Tg, Es, creep resistance, and recovery properties, as well as the thermal stability of PA66 in an oxidizing atmosphere.
Absolute lymphocyte count recovery following initial acute myelogenous leukemia therapy: Implications for adoptive cell therapy
Authors: Molina John C. , Li Yimei , Otto William R. , Miller Tamara P. , Getz Kelly D. , Mccoubrey Carly , Ramos Mark , Krause Edward , Cao Lusha , Gramatges M. Monica , Rabin Karen , Scheurer Michael , Elgarten Caitlin W. , Myers Regina M. , Seif Alix E. , Fisher Brian T. , Shah Nirali N. , Aplenc Richard 
Published: November 2022

AbstractBackgroundAn adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T‐cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T‐cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T‐cell manufacturing feasibility in children and young adults with AML.ProcedureALC data were collected from an observational study of patients with newly diagnosed AML between the ages of 1 month and 21 years who received treatment between the years of 2006 and 2018 at one of three hospitals in the Leukemia Electronic Abstraction of Records Network (LEARN) consortium.ResultsAmong 193 patients with sufficient ALC data for analysis, the median ALC following induction 1 was 1715 cells/μl (interquartile range: 1166–2388), with successive decreases in ALC with each subsequent course. Similarly, the proportion of patients achieving an ALC >400 cells/μl decreased following each course, ranging from 98.4% (190/193) after course 1 to 66.7% (22/33) for patients who received a fifth course of therapy.ConclusionsThere is a successive decline of ALC recovery with subsequent courses of chemotherapy. Despite this decline, ALC values are likely sufficient to consider apheresis prior to the initiation of each course of upfront therapy for the majority of newly diagnosed pediatric AML patients, thereby providing a window of opportunity for T‐cell collection for those patients identified at high risk of relapse or with refractory disease.
Targeting peptide‐based quorum sensing systems for the treatment of gram‐positive bacterial infections
Authors: Milly Tahmina A. , Tal‐Gan Yftah 
Published: November 2022

AbstractBacteria utilize a cell density‐dependent communication system called quorum sensing (QS) to coordinate group behaviors. In Gram‐positive bacteria, QS involves the production of and response to auto‐inducing peptide (AIP) signaling molecules to modulate group phenotypes, including pathogenicity. As such, this bacterial communication system has been identified as a potential therapeutic target against bacterial infections. More specifically, developing synthetic modulators derived from the native peptide signal paves a new way to selectively block the pathogenic behaviors associated with this signaling system. Moreover, rational design and development of potent synthetic peptide modulators allows in depth understanding of the molecular mechanisms that drive QS circuits in diverse bacterial species. Overall, studies aimed at understanding the role of QS in microbial social behavior could result in the accumulation of significant knowledge of microbial interactions, and consequently lead to the development of alternative therapeutic agents to treat bacterial infectivity. In this review, we discuss recent advances in the development of peptide‐based modulators to target QS systems in Gram‐positive pathogens, with a focus on evaluating the therapeutic potential associated with these bacterial signaling pathways.
Stability profile of vimentin rod domain
Authors: Lilina Anastasia V. , Leekens Simon , Hashim Hani M. , Vermeire Pieter‐Jan , Harvey Jeremy N. , Strelkov Sergei V. 
Published: November 2022

AbstractIntermediate filaments (IFs) form an essential part of the metazoan cytoskeleton. Despite a long history of research, a proper understanding of their molecular architecture and assembly process is still lacking. IFs self‐assemble from elongated dimers, which are defined by their central “rod” domain. This domain forms an α‐helical coiled coil consisting of three segments called coil1A, coil1B, and coil2. It has been hypothesized that the structural plasticity of the dimer, including the unraveling of some coiled‐coil regions, is essential for the assembly process. To systematically explore this possibility, we have studied six 50‐residue fragments covering the entire rod domain of human vimentin, a model IF protein. After creating in silico models of these fragments, their evaluation using molecular dynamics was performed. Large differences were seen across the six fragments with respect to their structural variability during a 100 ns simulation. Next, the fragments were prepared recombinantly, whereby their correct dimerization was promoted by adding short N‐ or C‐terminal capping motifs. The capped fragments were subjected to circular dichroism measurements at varying temperatures. The obtained melting temperatures reveal the relative stabilities of individual fragments, which correlate well with in silico results. We show that the least stable regions of vimentin rod are coil1A and the first third of coil2, while the structures of coil1B and the rest of coil2 are significantly more robust. These observations are in line with the data obtained using other experimental approaches, and contribute to a better understanding of the molecular mechanisms driving IF assembly.
Development of charybdotoxin Q18F variant as a selective peptide blocker of neuronal BK(α + β4) channel for the treatment of epileptic seizures
Authors: Liu Xinlian , Tao Jie , Zhang Shuzhang , Lan Wenxian , Yao Yu , Wang Chunxi , Xue Hongjuan , Ji Yonghua , Li Guoyi , Cao Chunyang 
Published: November 2022

AbstractEpilepsy is the results from the imbalance between inhibition and excitation in neural circuits, which is mainly treated by some chemical drugs with side effects. Gain‐of‐function of BK channels or knockout of its β4 subunit associates with spontaneous epilepsy. Currently, few reports were published about the efficacy of BK(α + β4) channel modulators in epilepsy prevention. Charybdotoxin is a non‐specific inhibitor of BK and other K+ channels. Here, by nuclear magnetic resonance (NMR) and other biochemical techniques, we found that charybdotoxin might interact with the extracellular loop of human β4 subunit (i.e., hβ4‐loop) of BK(α + β4) channel at a molar ratio 4:1 (hβ4‐loop vs. charybdotoxin). Charybdotoxin enhanced its ability to prevent K+ current of BK(α + β4 H101Y) channel. The charybdotoxin Q18F variant selectively reduced the neuronal spiking frequency and increased interspike intervals of BK(α + β4) channel by π–π stacking interactions between its residue Phe18 and residue His101 of hβ4‐loop. Moreover, intrahippocampal infusion of charybdotoxin Q18F variant significantly increased latency time of seizure, reduced seizure duration and seizure numbers on pentylenetetrazole‐induced pre‐sensitized rats, inhibited hippocampal hyperexcitability and c‐Fos expression, and displayed neuroprotective effects on hippocampal neurons. These results implied that charybdotoxin Q18F variant could be potentially used for intractable epilepsy treatment by therapeutically targeting BK(α + β4) channel.
Probing the effect of glycosaminoglycan depletion on integrin interactions with collagen I fibrils in the native extracellular matrix environment
Authors: Roth Jonathan , Hoop Cody L. , Williams Jonathan K. , Hayes Robert , Baum Jean 
Published: November 2022

AbstractFibrillar collagen–integrin interactions in the extracellular matrix (ECM) regulate a multitude of cellular processes and cell signalling. Collagen I fibrils serve as the molecular scaffolding for connective tissues throughout the human body and are the most abundant protein building blocks in the ECM. The ECM environment is diverse, made up of several ECM proteins, enzymes, and proteoglycans. In particular, glycosaminoglycans (GAGs), anionic polysaccharides that decorate proteoglycans, become depleted in the ECM with natural aging and their mis‐regulation has been linked to cancers and other diseases. The impact of GAG depletion in the ECM environment on collagen I protein interactions and on mechanical properties is not well understood. Here, we integrate ELISA protein binding assays with liquid high‐resolution atomic force microscopy (AFM) to assess the effects of GAG depletion on the interaction of collagen I fibrils with the integrin α2I domain using separate rat tails. ELISA binding assays demonstrate that α2I preferentially binds to GAG‐depleted collagen I fibrils in comparison to native fibrils. By amplitude modulated AFM in air and in solution, we find that GAG‐depleted collagen I fibrils retain structural features of the native fibrils, including their characteristic D‐banding pattern, a key structural motif. AFM fast force mapping in solution shows that GAG depletion reduces the stiffness of individual fibrils, lowering the indentation modulus by half compared to native fibrils. Together these results shed new light on how GAGs influence collagen I fibril–integrin interactions and may aid in strategies to treat diseases that result from GAG mis‐regulation.
The alarmone ppGpp selectively inhibits the isoform A of the human small GTPase Sar1
Authors: Huang Qingqiu , Szebenyi Doletha M. E. 
Published: November 2022

AbstractTransport of newly synthesized proteins from endoplasmic reticulum (ER) to Golgi is mediated by coat protein complex II (COPII). The assembly and disassembly of COPII vesicles is regulated by the molecular switch Sar1, which is a small GTPase and a component of COPII. Usually a small GTPase binds GDP (inactive form) or GTP (active form). Mammals have two Sar1 isoforms, Sar1a and Sar1b, that have approximately 90% sequence identity. Some experiments demonstrated that these two isoforms had distinct but overlapping functions. Here we found another instance of differing behavior: the alarmone ppGpp could bind to and inhibit the GTPase activity of human Sar1a but could not inhibit the GTPase activity of human Sar1b. The crystal structures of Sar1a⋅ppGpp and Sar1b⋅GDP have been determined. Superposition of the structures shows that ppGpp binds to the nucleotide‐binding pocket, its guanosine base, ribose ring and 5′‐diphosphate occupying nearly the same positions as for GDP. However, its 3′‐diphosphate points away from the active site and, hence, away from the surface of the protein. The overall structure of Sar1a⋅ppGpp is more similar to Sar1b⋅GDP than to Sar1b⋅GTP. We also find that the Asp140‐Arg138–water–ligand interaction net is important for the binding of ppGpp to Sar1a. This study provides further evidence showing that there are biochemical differences between the Sar1a and Sar1b isoforms of Sar1.
Time‐delay and parameter estimation for an ARX model based on copula theory and Armijo criterion and their applications in the modeling of the dynamics of the UAV
Authors: Jing Shaoxue , Chen Ling , Liu Ranran 
Published: November 2022

AbstractTime‐delay dynamic systems are widely existed in industrial applications owing to the measure, control or other processes. To carry out system analysis, control and fault diagnosis, the identification of time‐delay systems becomes more and more important. This article considers the identification of time‐delay ARX models based on a novel two‐stage algorithm. Firstly, a 2‐copula criterion based time‐delay estimation method is presented by using a measure of dependence between the model input and output. This method can obtain the time delay without the estimates of the parameters. Secondly, a multi‐gradient algorithm with adaptive stacking length is studied. This algorithm accelerates traditional stochastic gradient algorithm by taking several recent gradients in each iteration. The stacking length, that is, the number of the gradient used in a step, is determined by the Armijo criterion. The proposed algorithm is validated by numerical experiments and the modeling of unmanned aerial vehicle data.
Robust discrete‐time output feedback stabilization of integrator chains
Authors: Carvajal‐Rubio José Eduardo , Alarcón‐Carbajal Martín Alfredo , Sánchez‐Torres Juan Diego , Defoort Michael , Rubio‐Astorga Guillermo Javier , Castro‐Palazuelos David Enrique , Djemai Mohamed , Loukianov Alexander G. 
Published: November 2022

AbstractThis work proposes a discrete‐time output feedback controller to stabilize an integrator chain system in the presence of measurement noise and external disturbances. Besides, two structural systems are considered, the first one is a system with a saturation in the control input. The second one is a system with an unbounded input. Since the system output is supposed to be periodically sampled and noisy, a discrete‐time filtering observer is designed. Hence, using the output of the observer, a discrete‐time controller is derived. The closed‐loop system convergence and robustness analysis are also presented. Simulation results are performed, aiming to illustrate the main characteristics of the proposal, including comparisons between the closed‐loop system with an explicit and implicit discrete‐time observer. Finally, having proved the features of the implicit realization, the controller with an implicit differentiator is implemented to control a DC–DC buck converter.
Effects of rainfall characteristics on bromide leaching in a typical tobacco field in China's Yunnan Province
Authors: Zou Congming , Zhang Hui , Yang Yang , Liu Yingna , Sun Haowei , Gao Xiaofei 
Published: November 2022

AbstractKnowledge about water and solute transport in the vadose zone is critical for agrochemical management, especially for the tobacco cultivation characterized by extensive fertilizer and pesticide applications. Under the field conditions, however, natural soil heterogeneity complicates and limits the analysis of water and solute transport. Applying the scale‐dependent treatment distribution in a rainfall simulation experiment, the objective was to evaluate the impact of rainfall characteristics on bromide (Br−) leaching in a typical tobacco field in China's Yunnan Province. On a transect established with 24 plots, rainfall amount, intensity, and time delay relative to solute application were arranged in cyclic patterns at different spatial scales. Soil samples in 10‐cm increments down to 50 cm depth were collected for Br− determination after the simulated rainfall. The results display a significantly decreasing trend of Br− concentration with depth, suggesting the predominance of matrix diffusion over preferential flow at the scale of investigation in the intensively cultivated tobacco field. The Pearson correlation analysis only detected significant associations of Br− with rainfall intensity at the 0–10 cm depth and with rainfall amount at the 20–30 cm. With the aid of frequency‐domain analysis, by comparison, strong spatial correlations were revealed with rainfall characteristics at each depth, even with the presence of a plow pan at the depth of 30–40 cm due to deep tillage. Although the dominant control of Br− distribution varied with depth, these findings demonstrate the profound effects of rainfall characteristics on solute leaching and the usefulness of scale‐dependent treatment distribution in field‐scale investigations of solute transport as well as other hydrological processes.
Cluster analysis via random partition distributions
Authors: Dahl David B. , Andros Jacob , Carter J. Brandon 
Published: November 2022

AbstractHierarchical and k‐medoids clustering are deterministic clustering algorithms defined on pairwise distances. We use these same pairwise distances in a novel stochastic clustering procedure based on a probability distribution. We call our proposed method CaviarPD, a portmanteau from cluster analysis via random partition distributions. CaviarPD first samples clusterings from a distribution on partitions and then finds the best cluster estimate based on these samples using algorithms to minimize an expected loss. Using eight case studies, we show that our approach produces results as close to the truth as hierarchical and k‐medoids methods, and has the additional advantage of allowing for a probabilistic framework to assess clustering uncertainty. The method provides an intuitive graphical representation of clustering uncertainty through pairwise probabilities from partition samples. A software implementation of the method is available in the CaviarPD package for R.