Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is required for the V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. Ku heterodimer formed by Ku70 and Ku80 recognizes DSBs and facilitates the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, Paxx and Mri/Cyren) and downstream core factors subunits XLF, XRCC4 and Lig4. Accessory factors might be dispensable for the process depending on the genetic background and DNA lesion type. To determine the physiological role of Mri in DNA repair and development, we introduced frame-shift mutation in the Mri gene in mice. We then analyzed the development of Mri-deficient mice as well as wild type and immunodeficient controls. Mice lacking Mri possessed reduced levels of class switch recombination in B lymphocytes and slow proliferation of neuronal progenitors when compared to wild type littermates. Human cell lines lacking Mri were as sensitive to DSBs as WT controls. Overall, we concluded that Mri/Cyren is largely dispensable for DNA repair and mouse development.

Non-homologous end-joining (NHEJ) is a DNA repair pathway required to detect, process, and ligate DNA double-stranded breaks (DSBs) throughout the cell cycle. The NHEJ pathway is necessary for V(D)J recombination in developing B and T lymphocytes. During NHEJ, Ku70 and Ku80 form a heterodimer that recognizes DSBs and promotes recruitment and function of downstream factors PAXX, MRI, DNA-PKcs, Artemis, XLF, XRCC4, and LIG4. Mutations in several known NHEJ genes result in severe combined immunodeficiency (SCID). Inactivation of Mri, Paxx or Xlf in mice results in normal or mild phenotype, while combined inactivation of Xlf/Mri, Xlf/Paxx, or Xlf/Dna-pkcs leads to late embryonic lethality. Here, we describe three new mouse models. We demonstrate that deletion of Trp53 rescues embryonic lethality in mice with combined deficiencies of Xlf and Mri. Furthermore, Xlf^-/-Mri^-/-Trp53^+/- and Xlf^-/-Paxx^-/-Trp53^+/- mice possess reduced body weight, severely reduced mature lymphocyte counts, and accumulation of progenitor B cells. We also report that combined inactivation of Mri/Paxx results in live-born mice with modest phenotype, and combined inactivation of Mri/Dna-pkcs results in embryonic lethality. Therefore, we conclude that XLF is functionally redundant with MRI and PAXX during lymphocyte development in vivo. Moreover, Mri genetically interacts with Dna-pkcs and Paxx.

Non-homologous end-joining (NHEJ) is a major DNA repair pathway in mammalian cells that recognizes, processes and fixes DNA damages throughout the cell cycle, and is specifically important for homeostasis of post-mitotic neurons and developing lymphocytes. Neuronal apoptosis increases in the mice lacking NHEJ factors Ku70 and Ku80. Inactivation of other NHEJ genes, either Xrcc4 or Lig4, leads to massive neuronal apoptosis in the central nervous system (CNS) that correlates with embryonic lethality in mice. Inactivation of either Paxx, Mri or Dna-pkcs NHEJ gene results in normal CNS development due to compensatory effects of Xlf. Combined inactivation of Xlf/Paxx, Xlf/Mri and Xlf/Dna-pkcs, however, results in late embryonic lethality and high levels of apoptosis in CNS. To determine the impact of NHEJ factors on early stages of neurodevelopment, we isolated neural stem and progenitor cells from mouse embryos and investigated proliferation, self-renewal and differentiation capacity of these cells lacking either Xlf, Paxx, Dna-pkcs, Xlf/Paxx or Xlf/Dna-pkcs. We found that XLF, DNA-PKcs and PAXX maintain the neural stem and progenitor cell populations and neurodevelopment in mammals, which is particularly evident in the double knockout models.

Non-homologous end joining (NHEJ) is the main DNA repair mechanism for the repair of double strand breaks (DSBs) throughout the course of the cell cycle. DSBs are generated in developing B and T lymphocytes during V(D)J recombination to increase the repertoire of B and T cell receptors. DSBs are also generated during the class switch recombination (CSR) process in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. Thus, NHEJ is important for both V(D)J recombination and CSR. NHEJ comprises core Ku70 and Ku80 subunits that form the Ku heterodimer, which binds DSBs and promotes the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, PAXX, Mri) and downstream core factors (XLF, Lig4 and XRCC4). In recent decades, new NHEJ proteins have been reported, increasing complexity of this molecular pathway. Numerous in vivo mouse models have been generated and characterized to identify the interplay of NHEJ factors and their role in development of adaptive immune system. This review summarizes the currently available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development. We also underline genetic interactions and redundancy in the NHEJ pathway in mice.

Induction heating is a fast, reproducible, and efficient heating method used in various manufacturing processes. However, there is no established additive manufacturing (AM) process based on induction heating using wire as feedstock. This study investigates a novel approach to AM based on inductive heating, where a steel wire is melted and droplets are detached periodically using a two-winding induction coil. The process parameters and energy input into the droplets are characterized. The induction generator exhibits sluggish response to the excitation voltage, resulting in a lag in the coil current. The process is captured using a high-speed camera, revealing regular droplet formation and uniform size and shape when operated within an appropriate process window. Larger drops and increased spatter formation occur outside this window. The proposed method allows for the production of droplets with almost spherical shapes. Further analysis and characterization of droplet formation and energy input provide insights into process optimization and overall efficiency.

Pericentromeric regions of chromosomes enriched in tandemly repeated satellite DNA although representing a significant part of eukaryotic genomes are still understudied mainly due to interdisciplinary knowledge gaps. Recent studies suggest their important role in genome regulation, karyotype stability and evolution. Thus, the idea of satellite DNA as a junk part of the genome was refuted. Integration of data about molecular composition, chromosome behaviour and details of in situ organization of pericentromeric regions is of great interest. The objective of this work was a cytogenetic analysis of the interactions of pericentromeric regions non-homologous chromosomes in mouse spermatocytes using immuno-FISH. We analysed two events: the associations between cerntomeric regions of X chromosome and autosomes, and associations between centromeric regions of autosomal bivalents forming chromocenters. We conclude that X chromosome form temporary synaptic associations with different autosomes in early meiotic prophase I which normally can be found at pachytene-diplotene without signs of pachytene arrest. These associations are formed between the satellite DNA-enriched centomeric regions of X chromosome and different autosomes but not involve the satellite-poor centromeric region of Y-chromosome. We suggest the mechanism of X chromosome competitive replacement from such associations during synaptic correction. We showed that centromeric region of the X chromosome remains free of γH2Ax-dependent chromatin inactivation, while Y chromosome is completely inactivated. This findings highlights the predominant role of associations between satellite DNA-enriched regions of different chromosomes including X. We assume that X-autosome temporary associations is a manifestation of an additional synaptic disorders checkpoint. These associations are normally corrected before the late diplotene. We revealed that the intense spreading conditions applied to the spermatocytes I nuclei did not lead to destruction of stretched chromatin fibers i.e. elongated chromocenters enriched in satellite DNA. Revealed by us tight associations between pericentromeric regions of different autosomal bivalents and X chromosome may represent the basis for repeat stability maintenance in autosomes an X chromosome. The consequences of our findings are discussed. We obtained the preparations of mouse spermatocytes nuclei in the meiotic prophase I using two approaches: standard and extremely intense surface spread techniques. Using immuno-FISH we visualized tandemly repeated mouse Major and Minor satellite DNA located in the pericentromeric regions of chromosomes and performed a morphological comparison of the standard- and intensely spreaded meiotic nuclei. Based on our results, we assume the remarkable strength of the chromocenter-mediated associations, “chromatin “bridges”, between different bivalents at the pachytene and diplotene stages. We have demonstrated that the chromocenter “bridges” between the centromeric ends of meiotic bivalents are enriched in both tandemly repeated Major and Minor satellite DNA. Association of centromeric regions of autosomal bivalents and X-chromosome but not with Y-chromosome correlates with the absence of Major and Minor satellites on Y-chromosome. We suggest that revealed tight associations between pericentromeric regions of bivalents may represent the network-like system providing dynamic stability of chromosomal territories, as well as add new data for the hypothesis of ectopic recombination in these regions which supports sequence homogeneity between non-homologous chromosomes and does not contradict the meiotic restrictions imposed by the crossing-over interference near centromeres. We conclude that nuclear architecture in meio-sis may play an essential role in contacts between the non-homologous chromosomes providing the specific characteristics of pericentromeric DNA.

The European Green Deal poses a two-pronged challenge for the automotive industry: migrating to solutions based in light structures, requiring light weight concepts and light materials, while at the same time avoiding dependence towards the importation of these advanced materials. Aluminium alloys are lightweight and cost-effective materials that can successfully cover the requirements of many structural applications, however their production requires from bauxite and other Critical Raw Materials (CRM), such as Si and Mg. Aluminium alloys are fully recyclable, but scrap is usually contaminated and its use is related to an increment of impurities, tramp element and undesired inclusions. Traditionally, the use of secondary alloys has been restricted to low performance applications. The present work analyses the effect that the use of scrap has in the quantity of inclusions present in the alloy and in other properties relevant for the material processing. The study was carried out for common alloys belonging to 3 of the most common aluminium processes used in the car manufacturing industry: High Pressure Die Casting (HPDC) (EN AC-43500), extrusion (6063) and sheet metal forming (5754 and 6181). Reference alloy were mixed with different level of scrap (0, 20, 40, 60, 80 and 100%) trying to keep the chemical composition as unaffected as possible. The inclusions level of the alloy was characterized with the Prefil Foot-printer® test. In addition, the obtained materials, after being cast in an open mould, were subjected to metallographic characterization. Relevant properties to assess the formability quality of the alloys for the corresponding transforming process, were obtained: flowability test for HPDC alloy and high temperature compression for extrusion alloys. The results obtained suggest that the number of inclusions present in the melt highly increase with the amount of scrap used to produce the alloy. These inclusions are also related with an important lost of flowability, but do not have a noticeable impact on microstructure.

This paper presents the deformation of the joined sheet after the clinch-riveting process. The DX51D steel sheet with zinc coating was used. The samples to be joined with clinch riveting technology had a thickness of 1±0.05 mm and 1.5±0.1 mm. The sheet deformation was measured before and after the joining process. The rivet was pressed in the sheets with the same dimension between the rivet axis and three sheet edges: 20, 30 and 40 mm. For fixed segments of the die, from the rivet side close to the rivet, the sheet deformation was greater than that of the area with movable segments. The movement of die sliding element caused more sheet material to flow in the space between the fixed part of the die and movable segments. Hence, the sheet deformation in these places was smaller than for the die fixed element – sheet material was less compressed. For sheets thickness 1.5 mm and width 20 mm, the bulk of the sheet was observed. For a sheets width of 20 mm, it was observed that the deformation of the upper and lower sheets in the area of the rivet is greater than for sheets width of 30 or 40 mm.

Homologous recombination deficiency (HRD) has become an important prognostic and predictive biomarker for patients with high-grade serous ovarian cancer who may benefit from poly-ADP ribose polymerase inhibitors (PARPi) and platinum-based therapies. HRD testing provides relevant information to personalize patients’ treatment options, and it has been progressively incorporated in diagnostic laboratories. In this study, we evaluated the feasibility of in-house HRD testing deployable in a diagnostic clinical setting, comparing results from two commercially available next-generation sequencing (NGS)-based tumor tests (SOPHiA DDMTM HRD Solution and AmoyDx HRD Focus Panel) with the reference assay from Myriad MyChoice CDx. A total of 85 ovarian cancer samples were subjected to HRD testing. An overall strong correlation was observed across the three assays evaluated, regardless of the different underlying methods employed to assess genomic instability, with the highest pairwise correlation between Myriad and SOPHiA (R=0.87, p-value=3.39x10-19). The comparison of the assigned HRD status to the reference Myriad’s test revealed a positive predictive value (PPV) and negative predictive value (NPV) of 90.9% and 96.3% for SOPHiA’s test, while AmoyDx’s test achieved 75% PPV and 100% NPV. This is the largest HRD testing evaluation using different methodologies and provides a clear picture of the robustness of NGS-based tests currently offered in the market. Our data show that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and it can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, being an ideal alternative to offer to a broader number of patients, while still maintaining high-quality standards at more accessible price tiers.

This paper addresses the analysis for the nonlinear vibration response of a rectangular tube with a flexible end and non-rigid acoustic boundaries. This is a further work of the linear structural acoustic problem in a well-known acoustic book. In fact, the acoustic boundaries of an enclosed space sometimes are non-rigid and the structural vibration responses are nonlinear. These two points are the focuses of this paper. The multi-level residue harmonic balance method is applied to this nonlinear structural acoustic problem. The results obtained from the multi-level residue harmonic balance method and numerical method are generally in good agreement. The effects of excitation magnitude, tube length, and phase shift parameter etc. are examined.

We introduce NodeFlow, a flexible framework for probabilistic regression on tabular data that combines Neural Oblivious Decision Ensemble (NODE) and Conditional Continuous Normalizing Flows (CNF). It offers improved modeling capabilities for arbitrary probabilistic distributions, addressing the limitations of traditional parametric approaches. In NodeFlow, the NODE captures complex relationships in tabular data through a tree-like structure, while the conditional CNF utilizes the NODE’s output space as a conditioning factor. The training process of NodeFlow employs standard gradient-based learning, facilitating end-to-end optimization of the NODEs and CNF-based density estimation. This approach ensures outstanding performance, ease of implementation, and scalability, making NodeFlow an appealing choice for practitioners and researchers. Comprehensive assessments on benchmark datasets underscore NodeFlow’s efficacy, revealing its achievement of state-of-the-art outcomes in multivariate probabilistic regression setup and its strong performance in univariate regression tasks. Furthermore, ablation studies are conducted to justify the design choices of NodeFlow. In conclusion, NodeFlow’s end-to-end training process and strong performance make it a compelling solution for practitioners and researchers. Additionally, it opens new avenues for research and application in the field of probabilistic regression on tabular data.

Fire is a serious security threat that can lead to casualties, property damage, and environmental damage. However, despite the availability of object detection algorithms, challenges persist in detecting fires and smoke. These challenges include slow convergence speed, poor performance in detecting small targets, and high computational cost limiting deployments. In this paper, Fire smoke and human detection based on ConvNeXt and Mixed encoder (FCM-DETR), an end-to-end object detection algorithm based on Deformable DETR, is proposed. Firstly, we introduce ConvNeXt to take the place of Resnet, which greatly reduces the amount of computation and improves the ability to extract irregular flame features. Secondly, to effectively process multi-scale features, the original encoder is decoupled into two modules. Then Mixed encoder, an innovative encoder structure, is proposed, resulting in excellent performance of multi-scale fire and smoke features fusion. What can’t be overlooked is that the encoder block is compatible with any DETR-based models. Finally, the convergence speed is accelerated and the mean of average precision is improved by applying a novel loss function called Powerful IoU v2. The experimental results indicate that our model achieves the best detection accuracy compared to other models, with mAP reaching 66.7%, mAPs and Accuracyfire achieving impressive 50.2% and 98.05%, respectively.

Relative contribution of different repair pathways to the radiation-induced DNA damage responses remains a challenging issue of studying the radiation injury endpoints. Comparative manifestation of homologous recombination (HR) after application of different radiation doses greatly determines an overall effectiveness of recovery in dividing cell after irradiation, since HR is an error-free mechanism intended for repair of DNA double strand breaks (DSB) during S/G2 phases of cell cycle. In this article, we present an experimentally observed evidence of dose-dependent shift in relative contribution of HR in human fibroblasts after X-ray exposure at doses 20-1000 mGy, which is also supported by quantitative modeling of DNA DSB repair. Our findings indicate that the radiation dose increase leads to dose-dependent decrease in relative contribution of HR into the entire repair process.

In the field of railroad safety, effective detection of surface cracks is critical, necessitating reliable, high-speed non-destructive testing (NDT) methods. This study introduces a hybrid Eddy Current Testing (ECT) probe, specifically engineered for railroad inspection, to address the common issue of ’lift-off noise’ due to varying distances between the probe and test material. Unlike traditional ECT methods, this probe integrates transmit and differential receiver coils, aiming to enhance detection sensitivity and minimize lift-off impact. The study optimizes ECT probes employing different driver coils, emphasizing three main objectives: a) quantitatively evaluating each probe using signal- to-noise ratio (SNR) and outlining a real-time data processing algorithm based on SNR methodology; b) exploring the frequency range proximal to the electrical resonance of the receiver coil; c) examining sensitivity variations across varying lift-off distances. The experimental outcomes indicate that the newly designed probe with figure 8-shape driver coil significantly improves sensitivity in detecting surface cracks on railroads. It achieves an impressive SNR exceeding 100 for defects with minimal dimensions of 1 mm in width and depth. Simulation results closely align with experimental findings, validating the investigation of optimal operational frequency and lift-off distance for selected probe performance, determined to be 0.3 MHz and 0.5 mm, respectively. The realization of this project would lead to notable advancements in enhancing railroad safety by improving crack detection efficiency.

Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy, largely due to metastasis and drug resistant recurrences. Fifteen percent of ovarian tumors carry mutations in BRCA1 or BRCA2, rendering them vulnerable to treatment with PARP inhibitors such as olaparib. Recent studies have shown that TGFβ can induce “BRCAness” in BRCA wild-type cancer cells. Given that TGFβ is a known driver of epithelial to mesenchymal transition (EMT), and the con-nection between EMT and metastatic spread in EOC and other cancers, we asked if TGFβ and EMT alter susceptibility of EOC to PARP inhibition. Epithelial EOC cells were transiently treated with soluble TGFβ and their clonogenic potential, expression and function of EMT and DNA repair genes, and response to PARP inhibitors compared with untreated controls. A second epithelial cell line was compared to its mesenchymal derivative for EMT and DNA repair gene expression and drug responses. We found that TGFβ and EMT resulted in downregulation of genes responsible for homologous recombination (HR) and sensitized cells to olaparib. HR efficiency was reduced in a dose-dependent manner. Furthermore, mesenchymal cells displayed sensitivity to olaparib, cis-platin, and the DNA-PK inhibitor Nu-7441. Therefore, treatment of disseminated, mesenchymal tumors may represent an opportunity to expand clinical utility of PARP inhibitors and similar agents.

End-to-end learned image compression codecs have notably emerged in recent years. These codecs have demonstrated superiority over conventional methods, showcasing remarkable flexibility and adaptability across diverse data domains while supporting new distortion losses. Despite challenges such as computational complexity, learned image compression methods inherently align with learning-based data processing and analytic pipelines due to their well-suited internal representations. The concept of Video Coding for Machines has garnered significant attention from both academic researchers and industry practitioners. This concept reflects the growing need to integrate data compression with computer vision applications. In light of these developments, we present a comprehensive survey and review of lossy image compression methods. Additionally, we provide a concise overview of two prominent international standards, MPEG Video Coding for Machines and JPEG AI. These standards are designed to bridge the gap between data compression and computer vision, catering to practical industry use cases.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer. Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs. Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated. This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair

Mechanically homogenized composite of expanded graphite and cobalt(II) rhenate(VII) has been described. Cobalt(II) rhenate(VII) was obtained in a reaction of perrhenic acid with cobalt(II) nitrate. A simple mortar homogenization method was used to enhance intercalation of cobalt species within carbon matrix. The specific capacity of composite was enhanced by 50% in comparison to bare expanded graphite. The electrochemical characteristic was significantly improved including better cyclability, lower resistance of electrode material, lower iR drop, with respect to expanded graphite without cobalt(II) rhenate(VII) active species. Expanded graphite with its unique specific surface area and pore size diameter was proved as potential and cheap carbon support.

Few prior works study self-driving cars by deep learning with IoT collaboration. SDC-Net, which is an end-to-end multitask self-driving car camera cocoon IoT-based system, is one of the research that tackles this direction. However, by design SDC-Net is not able to identify the accident locations, it only classifies if it is a crash scene or not. In this work, we introduce an enhanced design for the SDC-Net system by 1) replacing the classification network with a detection one, 2) adapting our benchmark dataset labels built on the CARLA simulator to include the vehicles bounding boxes while keeping the same training, validation, and testing samples, 3) modifying the shared information via IoT to include the accident location. We keep the same path planning and automatic emergency braking network, the digital automation platform, and the input representations to formulate the comparative study. SDC-Net++ system is proposed to 1) output the relevant control actions, especially in case of accidents: accelerate, decelerate, maneuver, and brake, and 2) share the most critical information to the connected vehicles via IoT, especially the accident locations. A comparative study is also conducted between SDC-Net and SDC-Net++ with the same input representations: front camera only, panorama and bird-eye views, and with single-task networks: crash avoidance only, and multitask networks. Multitask network with a BEV input representation outperforms the nearest representation in precision, recall, f1-score, and accuracy by more than 15.134%, 12.046%, 13.593%, and 5%, respectively. SDC-Net++ multitask network with BEV outperforms SDC-Net multitask with BEV in precision, recall, f1-score, accuracy, and average MSE by more than 2.201%, 2.8%, 2.505%, 2%, and 18.677% respectively.

Sialylated milk oligosaccharides (SMOs) is the most important oligosaccharides in human milk oligosaccharides (HMOs), and have a multifunctional health benefit, and the most abundant SMOs are sialyllactose (SLs). The previous studies indicate that the growth of tumor cells, and angiogenesis on tumor tissues with Lewis lung carcinoma, melanoma, and colon carcinoma cells could be prevented by SL. Thus, it has been proposed that SL might be an ideal candidate for the development of anti-angiogenic drugs without any side effects. It has been proposed that the Sialic acid (Sia) can be produced through SL’s hydrolysis, and the dietary Sia is further transported to the brain and other tissues though blood for formation of CMP-Sia, the activated precursor of Sia, and then is catalyzed by polysialyltransferases (polySTs) for synthesis of polysialic acid (polySia) or polysialylation of neural cell adhesion molecule (NCAM). Thus, it’s necessary to study and develop new inhibitors, which not only modulate a proper balance between the gut health and neuros system development, but also inhibit the overexpression of polySia, and thus block the tumor cell migration. In this study, we proposed that 3’-SL and 6’-SL may be more ideal inhibitors comparing with two previous inhibitors, the low molecular weight heparin (LMWH) and cytidine monophosphate (CMP) in the previous studies.

Traditional methods of non-metallic materials joining for industrial uses are limited to lasers, or induction or conduction heating. The precision and efficiency for large-scale applications are difficult to be achieved at the same time. Here in this paper, we report a precise microwave welding method induced by localized surface plasmon of metallic macro-gaps under microwave excitation. The proposed method utilizes energy from well-developed commercial microwaver, and benefits from the precision of localized surface plasmon, an oscillating electron cloud excited by electromagnetic waves, which is currently under hot investigation only at micro- or nano-scales. The method is applied to the welding of polymers to solve the problems of complex processing equipment and high processing energy consumption in the traditional welding process, so as to cope with the growing energy and environmental crisis. Finite element numerical simulations are used to study the distribution characteristics of electric fields and temperature fields. The results show that the process is a high quality, efficient, low consumption and environmentally friendly green process compared to traditional polymer welding methods.

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics, powered by skin tissue engineering, offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM), is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and with aggressive in the clinic. Thus, it’s important to select a proper drug to block tumor cell migration for clinic treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a more ideal candidate for inhibition of NCAM polysialylation comparing with CMP and low molecular weight heparin (LMWH), which were determined based on our NMR studies. On the other hand, because neutrophil extracellular traps (NET) is the most dramatic stage in cell death process, and NETs’ release are related to pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis and vascular disorders. In this study, the molecular mechanism of inhibition of NETs’ release using LFcinB11 as inhibitor was also determined. Based on these results, LFcinB11 is proposed to be bifunctional inhibitor for inhibiting both NCAM polysialylation and NETs releases.

Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underly chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei followed by incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA-repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in Sonic-Hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA-repair genes resulting in chromosome instability and chromothripsis-like rearrangements.

Radiation therapy (RT) is one of the main approaches of cancer therapy, including non-small cell lung cancer (NSCLC). Radiation-induced DNA double-stranded breaks (DSBs), single-stranded DNA breaks (SSBs) and oxidized nucleobases cause replication fork stalling, chromosomal instability or point mutagenesis and can lead to cell death. Translesion DNA synthesis (TLS) is one of the DNA damage tolerance (DDT) pathways promoting replication of damaged DNA. Here, we explored the effects of the knockout of primase-polymerase PRIMPOL (PRIMPOL −/−) and TLS polymerase POLI (POLI −/−) genes in two different monoclonal lines derived from human NSCLC A549 cells. Our study aimed to investigate the impact of their absence on the susceptibility of these cells to ionizing radiation (IR)-induced stress. Without IR, cells that do not have PRIMPOL or POLI experience a considerable rise in apoptosis by day 7 of continuous cultivation and a noteworthy decline in cell migration under spatial confinement when compared to the parental wild-type cells. Despite this, we have found that PRIMPOL −/− exhibited higher clonogenic survival compared to wild-type cell lines in response to IR stress. Both of these cell lines demonstrated remarkable resilience to radiation stress, surpassing the survival rate of the original A549 cells. POLI deficiency reduces cellular γH2AX foci accumulation, while the presence of highest number of γH2AX foci in PRIMPOL−/− cells was ATM-independent. We report for the first time that increased post-irradiation clonogenic survival of PRIMPOL −/− A549 cells might be associated with the increase of CD133+ but not CD44+ populations of cancer stem-like cells.

We propose novel spectrometer designs that aim to enhance the measured spectral range 1 of ions on a finite-sized detector. In contrast to the traditional devices that use uniform magnetic 2 field, in which the deflection of particles increases inversely proportional to their momentum, in a 3 gradient magnetic field, the deflection of particles will be decreased due to the reduction of the 4 magnetic field along their propagation. Low energy ions are particularly impacted, as they are 5 deflected less and are more likely to reach the detector compared to being driven out of it while 6 using a uniform magnetic field. By the means of a gradient magnetic field, the nonlinear dispersion 7 of ions in a homogeneous magnetic field can approach a nearly linear dispersion. Nonetheless, 8 the dispersion of low energy ions in a homogeneous magnetic field remains unnecessarily high. 9 In this article, we explore linear, quadratic, and higher-order field profiles in comparison to the 10 homogeneous field case. We discuss the employed methodology and present simulation results of 11 the spectrometer with an extended ion spectral range, focusing on the minimum detectable energy 12 (energy dynamic range) and energy resolution

As one of the typical deposits in Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province, the Daliangzi Pb-Zn deposit has a close genetic relation with the structural system of “black/fracture zone” formed under the action of NWW-approx. EW strike-slip structures in the metallogenic province, but the mechanism of rock and ore-controlling action of the structural system remains unclear. Based on detailed analysis of tectonite-mineralized alteration lithofacies of R1 “black/fracture zone”, the tectonite-mineralized alteration lithofacies zones can be divided into 4 types in succession outward from the Pb-Zn mineralization center, i.e., ① brecciated and stockwork-like Pb-Zn mineralization-complex breccia facies zone, ② stockwork-like Pb-Zn mineralization-simple breccia and cataclasite facies zone, ③ veined pyrite-sulfide-dolomitic cataclasite facies zone, and ④ fine-veined calcite-black carbonized dolomite facies zone; Cl- and SO42--rich high-temperature oxidizing ore-bearing fluid mixes with reducing fluid in Zone ① while migration and precipitation occur in Zone ④. With the evolution of ore-forming fluid, the homogenization temperature decreases from Zone ① to Zone ④, the salinity increases from Zone ① to Zone ② and then decreases to Zones ③ and ④, and the fluid density has little change on the whole; the contents of Zn, Pb, Cu, Ga, Ge, Cd, Ag, and other metallogenic elements, the Zn/Pb ratio, and the CaO/MgO mole ratio decrease gradually from Zone ① to Zone ④; and REE fractionation, calcilization, silicification, and pyritization enhance gradually from Zone ① to Zone ④. This series of changes are the product of diapirism (cryptoexplosion) of strike-slip structures and “black/fracture zone”, among which the second-order structures (F5, F100, and other faults) derived from NWW-approx. EW striking dextral shear-tension faults F1 and F15 control the brecciated and stockwork-like Pb-Zn mineralized complex breccia facies zones and the stockwork-like Pb-Zn mineralized simple breccia and cataclasite facies zones. Therefore, this paper establishes the zoning mode of tectonite-mineralized alteration lithofacies of “black/fracture zone” and proposes that Zones ① and ② are important prospecting criteria. conclusions.

COVID-19, caused by SARS-CoV-2, was first identified in China in 2019. The exact origin of the disease remains uncertain, with theories suggesting it may have emerged from animals or accidentally leaked from a research laboratory. If the hypothesis that COVID-19 originated from a research laboratory is accurate, it is crucial to investigate potential pathways for pathogens to escape from biocontainment research animal facilities (BRAFs). We examine key biosafety issues associated with BRAFs, including inadequate decontamination procedures for water and experimental samples, handling high biosafety level pathogens in lower level laboratories, risks of animal bites and sharps injuries, contamination of bedding and enrichment materials, and improper management and transportation of biohazard samples. Additionally, we discuss the role of veterinarians in African research animal facilities and the challenges they encounter in maintaining biocontainment standards. We emphasize the importance of routine monitoring of effluent water to detect possible disease outbreaks. We recommend a thorough investigation of the COVID-19 pandemic to identify potential sources of pathogen release from BRAFs, which could serve as hotspots for future disease outbreaks. Findings from such investigations will inform the development of policies aimed at safeguarding human populations from future pandemics and preventing BRAFs from becoming sources of infectious disease outbreaks.

Existing methods for 3D human pose estimation mainly divide the task into two stages. The first stage identifies the 2D coordinates of the human joints in the input image, namely the 2D human joint coordinates. The second stage uses the results from the first stage as input to recover the depth information of human joints from the 2D human joint coordinates to achieve 3D human pose estimation. However, the recognition accuracy of the two-stage method relies heavily on the results of the first stage and includes too many redundant processing steps, which reduces the inference efficiency of the network. To address these issues, we propose the EDD, a fully End-to-end 3D human pose estimation method based on transformer architecture with Dual Decoders. By learning multiple human poses, the model can directly infer all 3D human poses in the image using a pose decoder, and then further optimize the recognition result using a joint decoder based on the kinematic relations between joints. With the attention mechanism, this method can adaptively focus on the most relevant features to the target joint, effectively overcoming the feature misalignment problem in the human pose estimation task and greatly improving the model performance. Any complex post-processing step, such as non-maximum suppression, is eliminated, further improving the efficiency of the model. The results show that the method achieves an accuracy of 87.4% on the MuPoTS-3D dataset, significantly improving the accuracy of end-to-end 3D human pose estimation methods.

First described in 1760 by the anatomist Morgagni, CoA is a congenital heart defect characterized by narrowing the aorta, typically distal to the left subclavian artery. It accounts for approximately 5-8% of all congenital heart diseases, with an incidence estimated at 4 per 10,000 live births. In 1944, the Swedish surgeon Clarence Crafoord achieved the first successful surgical CoA repair by performing an aortic end-to-end anastomosis on two patients aged 12 and 27 years old. Presently, the most prevalent techniques for surgical repair, particularly in infants and neonates with isolated coarctation, involve resection with end-to-end anastomosis (EEA) and the modified Crafoord technique (extended resection with end-to-end anastomosis (EEEA)). Subclavian flap aortoplasty (SCAP) is an alternative surgical option for CoA repair in patients under two years of age. In cases where the stenosis extends beyond resection and end-to-end anastomosis feasibility, patch aortoplasty (PP) employing a prosthetic patch can augment the stenotic region, especially for older patients. Despite advances in pediatric cardiology and cardiac surgery, recoarctation remains a significant concern after surgical or interventional repair. This comprehensive review aims to provide a thorough analysis of coarctation management, covering the pioneering techniques introduced by Crafoord using head-to-tail anastomosis and now extending to the contemporary era marked by percutaneous interventions as well as the recoarctation rate associated with each type.

We present TOLGAN that generates traditional oriental landscape (TOL) image from a map that specifies the locations and shapes of the elements composing TOL. Users can create a TOL map by using a user interface or a segmentation scheme from a photograph. We design the generator of TOLGAN as a series of decoding layers where the map is applied between the layers. The generated TOL image is further enhanced through an AdaIN architecture. The discriminator of TOLGAN processes a generated image and its groundtruth TOL artwork image. TOLGAN is trained through a dataset composed of paired TOL artwork images and their TOL maps. We present a tool through which users can produce a TOL map by specifying and organizing the elements of TOL artworks. TOLGAN successfully generates a series of TOL images from the TOL map. We evaluate our approach using a quantitative way by estimating FID and ArtFID scores and a qualitative way by executing two user studies. Through these studies, we prove the excellence of our approach by comparing our results with those from several important existing works.

In Holter monitoring, the precise detection of standard heartbeats and Ventricular Premature Contractions (PVCs) is paramount for accurate cardiac rhythm assessment. This study introduces a novel application of the 1D U-Net neural network architecture aimed at enhancing PVC detection in Holter recordings. Training data comprised the Icentia11k, INCART DB, and our custom dataset. The model’s efficacy was subsequently validated against traditional Holter analysis methodologies across multiple databases, including AHA DB, MIT 11 DB, NST, and another custom dataset encompassing challenging real-world examples. The results underscored the 1D U-Net model’s prowess in QRS complex detection, achieving near-perfect balanced accuracy scores across all databases. PVC detection exhibited variability, with balanced accuracy scores ranging from 0.909 to 0.986. Despite some databases, like the AHA DB, showcasing lower sensitivity metrics, their robust balanced accuracy accentuates the model’s equitable performance in discerning both false positives and negatives. In conclusion, while the 1D U-Net architecture is a formidable tool for QRS detection, there’s a clear avenue for further refinement in its PVC detection capability, given the inherent complexities and noise challenges in real-world PVC occurrences.

Autonomous driving vehicles rely on sensors for the robust perception of surroundings. Such vehicles are equipped with multiple perceptive sensors with a high level of redundancy to ensure safety and reliability in any driving condition. However, multi-sensor, such as camera, LiDAR and radar, systems bring up the requirements related to sensor calibration and synchronization, which are the fundamental blocks of any autonomous system. On the other hand, sensor fusion and integration have become important aspects of autonomous driving research and directly determine the efficiency and accuracy of advanced functions such as object detection and path planning. Classical model-based estimation and data-driven models are two mainstream approaches to achieving such integration. Most recent research is shifting to the latter, showing high robustness in real-world applications but requiring large quantities of data to be collected, synchronized, and properly categorized. To generalize the implementation of the multi-sensor perceptive system, we introduce an end-to-end generic sensor dataset collection framework that includes both hardware deploying solutions and sensor fusion algorithms. The framework prototype integrates a diverse set of sensors, such as cameras, LiDAR, and radar. Furthermore, we present a universal toolbox to calibrate and synchronize three types of sensors based on their characteristics. The framework also includes the fusion algorithms, which utilize the merits of three sensors , namely, camera, LiDAR and radar, and fuse their sensory information in a manner that is helpful for object detection and tracking research. The generality of this framework makes it applicable in any robotic or autonomous applications, also suitable for quick and large-scale practical deployment.

While thunderstorms can pose severe risks to property and life, forecasting remains challenging, even at short lead times, as these often arise in meta-stable atmospheric conditions. In this paper, we examine the question of how well we could perform short-term (up to 180min) forecasts using exclusively multi-spectral satellite images and past lighting events as data. We employ representation learning based on deep convolutional neural networks in an “end-to-end” fashion. Here, a crucial problem is handling the imbalance of the positive and negative classes appropriately in order to be able to obtain predictive results (which is not addressed by many previous machine-learning-based approaches). The resulting network outperforms previous methods based on physically-based features and optical flow methods (similar to operational prediction models) and generalizes across different years. A closer examination of the classifier performance over time and under masking of input data indicates that the learned model actually draws most information from structures in the visible spectrum, with infrared imaging sustaining some classification performance during the night.

We show that the respective oversights in the von Neumann's general theorem against all hidden variable theories and Bell's theorem against their local-realistic counterparts are homologous. Both theorems unjustifiably assume the additivity of expectation values within hidden variable theories to derive their respective conclusions. However, for non-commuting observables, the equivalence of a sum of expectation values and the expectation value of the sum of measurement results, although respected within quantum mechanics, need not hold for hidden variable theories, regardless of specific characteristics such as local realism they may respect. Once this oversight is ameliorated from Bell's argument and local realism is implemented correctly, the bounds on the CHSH correlator work out to be +/-2\/2 instead of +/-2, thereby mitigating the conclusion of Bell's theorem. Consequently, what is ruled out by the Bell-test experiments is not local realism but the additivity of expectation values.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

It is time-consuming for acquiring complete data by fully phase encoding in two orthogonal directions along with one frequency encoding direction. Undersampling in the 3D k-space is promising in accelerating such 3D MRI process. Though 3D undersampling can be conducted according to predefined probability density, the density based method is not optimal. Because of the large amount of 3D data and computational cost, it is challenging to perform data-driven and learning-based 3D undersampling and subsequent 3D reconstruction. To tackle this challenge, this paper proposes a deep neural network called EEUR-Net, realized by optimizing specific undersampling patterns for the fully-sampled 3D k-space data. Innovatively, our undersampling algorithm employs an end-to-end deep learning approach to optimize phase encoding patterns and uses a 3D U-Net for image reconstruction of undersampled data. Through end-to-end training, we obtain an optimized 3D undersampling pattern, which significantly enhances the quality of the reconstructed image under the same acceleration factor. A series of experiments on a knee MRI dataset demonstrated that, in comparison to standard random uniform, radial, Poisson and equispaced Cartesian undersampling schemes, our end-to-end learned undersampling pattern considerably improves the reconstruction quality of undersampled MRI images.

Owing to the expansion of non-face-to-face activities, security issues in video conferencing systems are becoming more critical. In this paper, we focus on the end-to-end encryption (E2EE) function among security services of video conferencing systems. First, the E2EE-related protocols of Zoom and Secure Frame (SFrame), which are representative video conferencing systems, are thoroughly investigated, and the two systems are compared and analyzed overall. Next, the E2EE protocol in the Government Public Key Infrastructure (GPKI)-based video conferencing system, in which the user authentication mechanism is fundamentally different from those used in private sector systems, such as Zoom or SFrame, will be considered. In particular, among E2EE-related protocols, we propose a detailed mechanism in which the post-quantum cryptography (PQC) key encapsulation mechanism (KEM) is applied to the user key exchange process. As the session key is not disclosed to the central server even in futuristic quantum computers, the mechanism to which the PQC KEM method proposed in this study is applied satisfies the E2EE security requirements and can be applied to domestic GPKI-based systems. It is expected to contribute in strengthening the safety of the next-generation video conferencing system.

Radio Frequency Interference (RFI) detection and characterization play a critical role to in ensuring the security of all wireless communication networks. Advances in Machine Learning (ML) have led to the deployment of many robust techniques dealing with various types of RFI. To sidestep an unavoidable complicated feature extraction step in ML, this paper proposes an efficient end-to-end method using the latest advances in deep learning to extract the appropriate features of the RFI signal. Moreover, this study utilizes the benefits of transfer learning to determine both the type of received RFI signals and their modulation types. To this end, the scalogram of the received signals is used as the input of the pre-trained convolutional neural networks (CNN), followed by a fully-connected classifier. This study considers a digital video stream as the signal of interest (SoI), transmitted in a real-time satellite-to-ground communication using DVB-S2 standards. To create the RFI dataset, the SoI is combined with three well-known jammers namely, continuous-wave interference (CWI), multi- continuous-wave interference (MCWI), and chirp interference (CI). This study investigated four well-known pre-trained CNN architectures, namely, AlexNet, VGG-16, GoogleNet, and ResNet-18, for the feature extraction to recognize the visual RFI patterns directly from pixel images with minimal preprocessing. Moreover, the robustness of the proposed classifiers is evaluated by the data generated at different signal to noise ratios (SNR).

Photophysical properties of a series of bis(arylydene)cycloalkanone dyes with various donor substituentns are studied by quantum chemistry. Their capacity for luminescence and nonradiative relaxation through trans-cis isomerization is related to their structure, in particular, to the donor capacity of the substituents and the degree of conjugation due to the central cycloalkanone moiety. It is shown that cyclohexanone central moiety introduces distortions and disrupts the conjugation, thus leading to a nonmonotonic change in their properties. The increasing donor capacity of the substituents causes increase in the HOMO energy (raise of the oxidation potential) and decrease in the HOMO-LUMO gap, which results in the red shift of the absorption spectra. The ability of the excited dye to relax through fluorescence or through trans-cis isomerization is governed by the height of the barrier between the Franck–Condon and S1-S0 conical intersection regions on the potential energy surface of the lowest π-π* excited state. This barrier also correlates with the donor capacity of the substituents and the degree of conjugation between the central and donor moieties. The calculated fluorescence and trans-cis isomerization rates are in good agreement with the observed fluorescence quantum yields.

Mitral valve disease is a common heart disease in dogs. The aim of this study was to describe the cases of dogs who underwent mitral valve repair using a v-clamp device and to provide their long-term follow-up data on cardiac function after mitral valve repair. Four dogs with mitral valve regurgitation who experienced coughing and dyspnea underwent surgical mitral valve repair between December 2023 and June 2024. The patients were evaluated by transthoracic and transesophageal echocardiography. Echocardiography revealed mitral valve leaflet regurgitation. Mitral valve repair was performed under general anesthesia using a v-clamp device introduced through an introducer wire guide. Echocardiography was conducted at baseline and the 6-month follow-up. Blood analysis results after surgical repair were normal. Follow-up echocardiography revealed no complications related to the procedure, with all dogs demonstrating improved respiratory signs and quality of life after repair. No adverse reactions were reported after surgery. A v-clamp device was used to repair mitral valve regurgitation in four dogs. Mitral valve repair using a v-clamp device is another treatment option for mitral valve disease in dogs.

Einstein’s publication of the Special Theory of Relativity in 1905 gave birth to the space-time model as a fundamental arena of the universe. Time has become 4th dimension of space and theoretically one could move backward and forward in time. Hypothetical time travel has been a hot topic of scientific discussion since Kurt Gödel published his article about closed time-like curves (CTC) in 1949. He was aware that his CTC model confirms that there is no physical time. Physicists understood his model as a theoretical frame for time travel. Recent research confirmed that universal space is time-invariant. Motion happens only in space and time is the duration of motion. Nobody can travel in time because time has no physical existence. Time as duration is an emergent physical quantity entering existence in the process of measurement of the duration of material change with clocks. The universal space is utterly timeless. There is no physical time in the universe.

Speech recognition, also known as automatic speech recognition (ASR), is a technology that enables software to transcribe spoken language into text. However, existing Amharic ASR methods require multiple separate blocks, such as language, acoustic, and pronunciation models with dictionaries, which can be time-consuming and influence performance. This study proposes an approach that replaces much of the speech pipeline with a single recurrent neural network (RNN) architecture. Our proposed architecture is based on a hybrid approach that combines a convolutional neural network (CNN) with a recurrent neural network (RNN) and a connectionist temporal classification (CTC) loss function. We conducted several experiments with noisy audio data that contain 20,000 valid sentences. The model was evaluated using the word error rate (WER) metric, achieving impressive results of 7% WER on noisy data. This approach has significant implications for the field of speech recognition, as it reduces the human effort required to create dictionaries and improves the efficiency and accuracy of ASR systems, making them more practical for real-world applications.

Alzheimer’s disease (AD) and the therapies of AD with anti-amyloid1-42 (Aβ) monoclonal antibodies are associated with the vascular complications of brain edema, hemorrhage, and cerebral amyloid angiopathy (CAA) termed amyloid-related imaging abnormalities (ARIAs). The neuropathology of normal and AD brains demonstrates that monocyte/macrophages (MMs) are critical in successful brain clearance in healthy brain by up-loading, transporting, and degrading Aβ but fail degradation and clearance in AD patients by releasing Aβ into vessels at the blood-brain barrier, causing vasculitis and ARIAs. The naturally-formed epoxides (EpFAs) of polyunsaturated fatty acids (PUFA’s), including arachidonic, docosahexaenoic, and eicosapentaenoic fatty acids, may repair degradation of Aβ by regulating Aβ-degrading enzymes, inflammatory cytokines, and unfolded protein response (UPR) to endoplasmic reticulum stress in a homeostatic fashion. EpFAs are, however, degraded by the soluble epoxide hydrolase enzyme (sEH) but are protected by the sEH inhibitor (sEHI) TPPU. In the cultures of AD patients’ macrophages, TPPU with the epoxide EEQ, and the cGAS/STING inhibitor H-151 increased uptake of Aβ at 2 hours and degradation of Aβ at 24 hours. In conclusion, the soluble epoxide hydrolase inhibitor TPPU with omega-3 fatty acids and the cGAS/STING inhibitor H-151 increase Aβ uptake and degradation in macrophages of AD patients, and potentially enhancing Aβ clearance in the AD brain.

At the end of the dry season in early March to early April each year, extensive agricultural biomass waste burnings occur throughout insular mainland Southeast Asia. During this biomass burnings period, smoke aerosols blanket the whole regions and were transported and dispersed by predominant westerly and south westerly winds to southern China, Taiwan and as far southern Japan and the Philippines. The extensive and intense burnings coincided with some wildfires in the forests due to high temperature making the region one of the global hot spots of biomass fires. In this study, we focus on the effect of pollutants emitted from biomass burnings in March 2019 at the height of the burnings period to the exposed population and their health impact. The Weather Research Forecast- Chemistry (WRF-Chem) model was used to predict the PM2.5 concentration over the simulating domain and health impacts are then assessed on the exposed population in the four countries of Southeast Asia, namely Thailand, Laos, Cambodia and Vietnam. Using the health impact based on log-linear concentration response function and Integrated Exposure Response (IER), the results show that at the peak period of the burnings from 13 to 20 March 2019, Thailand experienced the highest impact, with an estimated 2170 premature deaths. Laos, Vietnam, and Cambodia followed, with estimated mortalities of 277, 565, and 314 deaths respectively. However, when considering the impact per head of population, Laos exhibited the highest impact, followed by Thailand, Cambodia, and Vietnam. The results highlight the significant health impact and associated economic cost of agricultural waste burnings in Southeast Asia at the end of the dry season. And hence policy makers should take these into account to design measures to reduce the negative impact of widespread burnings on exposed population in the region.

Advanced glycation end-products (AGEs) form through non-enzymatic glycation of various proteins. Optic nerve degeneration is a frequent complication of diabetes, and retinal AGEs accumulation is strongly linked to diabetic retinopathy development. Type 2 diabetes mellitus (T2DM) is a major risk factor for Alzheimer's disease (AD), with patients often exhibiting optic axon degeneration in the nerve fiber layer. Notably, a gap exists in our understanding of how AGEs contribute to neuronal degeneration in the optic nerve within the context of both diabetes and AD. Our previous work demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (TAGE) disrupt neurite outgrowth through TAGE-β-tubulin aggregation and tau phosphorylation in neural cultures. In this study, we further illustrated GA-induced suppression of optic nerve axonal elongation via abnormal β-tubulin aggregation in mouse retinas. Elucidating this optic nerve degeneration mechanism holds promise for bridging the knowledge gap regarding vision loss associated with DM and AD.

The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly in gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5,397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests.

Autonomous driving navigation relies on diverse approaches, each with advantages and limitations depending on various factors. For HD maps, modular systems excel, while end-to-end methods dominate mapless scenarios. However, few leverage the strengths of both. This paper innovates by proposing a hybrid architecture that seamlessly integrates modular perception and control modules with data-driven path planning. This innovative design leverages the strengths of both approaches, enabling a clear understanding and debugging of individual components while simultaneously harnessing the learning power of end-to-end approaches. Our proposed architecture achieved 1st and 2nd place in the 2023 CARLA Autonomous Driving Challenge’s SENSORS and MAP tracks, respectively. These results demonstrate the architecture’s effectiveness in both map-based and mapless navigation.

The detection performance of small objects in remote sensing images has not been satisfactory compared to large objects, especially in low-resolution and noisy images. A generative adversarial network (GAN)-based model called enhanced super-resolution GAN (ESRGAN) showed remarkable image enhancement performance, but reconstructed images usually miss high-frequency edge information. Therefore, object detection performance showed degradation for small objects on recovered noisy and low-resolution remote sensing images. Inspired by the success of edge enhanced GAN (EEGAN) and ESRGAN, we applied a new edge-enhanced super-resolution GAN (EESRGAN) to improve the quality of remote sensing images and used different detector networks in an end-to-end manner where detector loss was backpropagated into the EESRGAN to improve the detection performance. We proposed an architecture with three components: ESRGAN, EEN, and Detection network. We used residual-in-residual dense blocks (RRDB) for both the ESRGAN and EEN, and for the detector network, we used a faster region-based convolutional network (FRCNN) (two-stage detector) and a single-shot multibox detector (SSD) (one stage detector). Extensive experiments on a public (car overhead with context) dataset and another self-assembled (oil and gas storage tank) satellite dataset showed superior performance of our method compared to the standalone state-of-the-art object detectors.

Several tumor types have been efficiently treated with PARPis, which are now approved for the treatment of ovarian, breast, prostate, and pancreatic cancer. The BRCA1/2 genes and mutations in many additional genes involved in the HR pathway may be responsible for the HRD phenomenon. In the present study, an NGS assay was used to analyze 513 genes associated with targeted and immuno-oncology therapies in 406 samples. In addition, the %gLOH values of 24 samples were also calculated using the Affymetrix technology to compare the results obtained by the two methodologies. HR variations occurred in 20.93% of the malignancies, while BRCA1/2 gene alterations in 5.17%. %LOH was highly correlated with alterations in the BRCA1/2 genes since 76.19% (16/21) of the BRCA1/2 positive tumors had a high %LOH value (p=0.007). Moreover, the LOH status was highly correlated with the TP53 and KRAS statuses, but there was no association with the TMB value. Lin's Concordance Correlation Coefficient for the 24 evaluable samples simultaneously examined by both assays was 0.87, indicating a nearly perfect agreement. In conclusion, the addition of gLOH analysis could assist the detection of additional patients eligible for PARPis

Speech recognition, or automatic speech recognition (ASR), is a technology designed to convert spoken language into text using software. However, conventional ASR methods involve several distinct components, including language, acoustic, and pronunciation models with dictionaries. This modular approach can be time-consuming and may influence performance. In this study, we propose a method that streamlines the speech recognition process by incorporating a unified recurrent neural network (RNN) architecture. Our architecture integrates a convolutional neural network (CNN) with an RNN and employs a connectionist temporal classification (CTC) loss function. Key experiments were carried out using a dataset comprising 576,656 valid sentences, using erosion techniques. Evaluation of the model performance, measured by the word error rate (WER) metric, demonstrated remarkable results, achieving a WER of 2%. This approach has significant implications for the realm of speech recognition, as it alleviates the need for labor-intensive dictionary creation, enhancing the efficiency and accuracy of ASR systems, and making them more applicable to real-world scenarios. For future enhancements, we recommend the inclusion of dialectal and spontaneous data in the dataset to broaden the model's adaptability. Additionally, fine-tuning the model for specific tasks can optimize its performance for targeted objectives or domains, further enhancing its effectiveness in those areas.

Lung cancer (LC) continues to be an important public health problem being the most common form of cancer and a major cause of cancer deaths worldwide. Despite the great bulk of research to identify genetic susceptibility genes by genome-wide association studies, only few loci associated to nicotine dependence have been consistently replicated. Our previously published study in few phenotypically discordant sib-pairs identified a combination of germline truncating mutations in known cancer susceptibility genes in never smoker early-onset LC patient does not present in their healthy sib. These results firstly demonstrated the presence of an oligogenic combination of disrupted cancer predisposing genes in non-smokers patients, giving experimental support to a model of a “private genetic epidemiology”. Here, we used a combination of whole-exome and RNA sequencing coupled with a discordant sib’s model in a novel cohort of pairs of never-smokers early-onset LC patients and in their healthy sibs used as controls. We selected rare germline variants predicted as deleterious by CADD and SVM bio-informatics tools and absent in the healthy sib. Overall, we identified an average of 200 variants per patient, about 10 of which in cancer predisposing genes. In most of them, RNA sequencing data reinforced the pathogenic role of the identified variants showing: i) downregulation in LC tissue (indicating “second hit” in tumor suppressor genes); ii) upregulation in cancer tissue (likely oncogene); iii) downregulation in both normal and cancer tissue (indicating transcript instability). The combination of the two techniques demonstrates that each patient has an average of six (with a range from four to eight) private mutations with functional effect in tumor predisposing genes. The presence of a unique combination of disrupting events in the affected subjects may explain the absence of familial clustering of non-small cell lung cancer. In conclusion, these findings indicate that each patient has his/her own “predisposing signature” to cancer development and suggest the use of personalized therapeutic strategies in lung cancer.

The focus of this work lies in the construction of monitoring system designed in the form of a patch using a long-lasting potentiometric electrolyte concentration sensor from metal electrodes, in a galvanic cell configuration Mg(s)|NaCl(aq)|Cu(s). Initially, a mathematical analysis was conducted on the expected sensor output through the Nernst equation. The experimental phase involved conducting controlled tests in the laboratory using various molar concentrations of sodium chloride (NaCl) in aqueous solution. Results showed that the electrolyte sensor allows for monitoring electrolyte levels in NaCl in the range of 0.02 to 1 M/L, with electrode lifespan exceeding 10 days. On the other hand, when patch is using human sweat during controlled exercise routines, it showed the sensor's capability for monitoring changes in the subjects' hydration levels in real time. The sensor output potential is greater than 1.7 volts when the sensor electrodes are in contact with human sweat, which is equivalent to measuring molar concentrations at normal hydration and moderately high hydration levels. Sensor results indicate that the system can function in a self-powered manner without external batteries. Additionally, the extended lifespan of its electrodes allows for continuous monitoring of imbalances in the human body, showcasing the system capability for long-term health assessment.

Autologous platelet-rich plasma (PRP) preparations are prepared at point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate) and, bioformulation dependent, also leukocyte and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support in numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and ultimately functional structural repair. Normally, after PRP preparation the PPP fraction is discarded. One of the less well known, but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation, fibrosis, and they promote keratinocyte migration and support in tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell-cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating in a fast and efficient manner plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional, total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein rich platelet concentrate (PRPC) biological preparation. After the activation of proteins, mainly fibrinogen, the PRPC matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), and the embedded concentrated PRP cells and molecules. The administered PRPC biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PRPC matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of PRPC matrix.

Endothelial cells are the crucial inner lining of blood vessels, pivotal in vascular homeostasis and integrity. However, these cells are perpetually subjected to a myriad of mechanical, chemical, and biological stresses that can compromise their plasma membranes. A sophisticated repair system involving key molecules, such as calcium, annexins, dysferlin, and MG53, is essential for maintaining endothelial viability. These components orchestrate complex mechanisms, including exocytosis and endocytosis, to repair membrane disruptions. Dysfunctions in this repair machinery, often exacerbated by aging, are linked to endothelial cell death, subsequently contributing to the onset of atherosclerosis and the progression of cardiovascular diseases (CVD) and stroke, major causes of mortality in the United States. Thus, identifying the core machinery for endothelial cell membrane repair is critically important for understanding the pathogenesis of CVD and stroke and developing novel therapeutic strategies for combating CVD and stroke. This review summarizes the recent advances in understanding the mechanisms of endothelial cell membrane repair. The future directions of this research area are also highlighted.

Background/Objectives Recurrent shoulder instability following Bankart lesion repair often necessitates surgical revision. Identified risk factors include young age, glenoid bone loss, and off-track Hill-Sachs lesions. This systematic review aims to understand failure rates of arthroscopic revision Bankart repair and if these aforementioned factors influence its success. Methods Following PRISMA guidelines, this systematic review, registered on PROSPERO, included twenty-four articles. Two independent reviewers assessed eligibility across three databases, focusing on recurrent instability as the primary endpoint, while also noting functional measures, adverse events, revision operations, and return-to-sport rates when available. Results Key surgical techniques for recurrent instability post-Bankart repair were identified, with revision arthroscopic Bankart being the most common (685/1032). Despite generally endorsed effectiveness, recurrence rates have increased over the past four years. Comparative analysis revealed significantly lower recurrence for open Latarjet compared to revision arthroscopic Bankart (p

The goal of the investigation is to increase coverage, which is ensure better transmission around IoT services using IRS within a two-tier 6G system comprising of one micro cell tier running beneath a macro cellular tier. As a result, the study tested and compared the reliability of traditional connectivity with IRS-enhanced connectivity in terms of upstream end-to-end latency using computer-based measuring methods. The study concluded that the implementation of IRS greatly improves coverage, which means transmission effectiveness, for 6G services.

In the leading/trailing edge’s adaptive machining of the near-net-shaped blade, a small portion of the theoretical part is retained for securing aerodynamic performance by manual work. However, this procedure is time-consuming and depends on the human experience. In this paper, we defined retained theoretical leading/trailing edge as the reconstruction area. To accelerate the reconstruction process, an anchor-free neural network model based on Transformer was proposed, named LETR (Leading/trailing Edge Transformer). LETR extracts image features from an aspect of mixed frequency and channel domain. We also integrated LETR with the newest meta-Acon activation function. We tested our model on the self-made dataset LDEG2021 on a single GPU and got an mAP of 91.9\%, which surpassed our baseline model, Deformable DETR by 1.1\%. Furthermore, we modified LETR’s convolution layer and named the new model after GLETR (Ghost Leading/trailing Edge Transformer) as a lightweight model for real-time detection. It is proved that GLETR has fewer weight parameters and converges faster than LETR with an acceptable decrease in mAP (0.1\%) by test results.

Imperfection sensitivity of large amplitude vibration of curved single-walled carbon nanotubes (SWCNTs) is considered in this study. The SWCNT is modeled as a Timoshenko nano-beam and its curved shape is included as an initial geometric imperfection term in the displacement field. Geometric nonlinearities of von Kármán type and nonlocal elasticity theory of Eringen are employed to derive governing equations of motion of nano-beam. Spatial discretization of governing equations and associated boundary conditions is performed using differential quadrature (DQ) method and the corresponding nonlinear eigenvalue problem is iteratively solved. Effects of value and location of the geometric imperfection, and the nonlocal small-scale parameter on the nonlinear frequency ratio and imperfection sensitivity of a curved SWCNT for various boundary conditions are investigated. The results show that the geometric imperfection plays a significant role in the nonlinear vibration characteristics of curved SWCNTs.

Steel fibre reinforced concrete (SFRC) consists of short hooked steel fibres randomly distributed and oriented within the cementitious matrix. The contribution of fibre in bridging cracks to provide the stress transfer required relies upon the orientation of the fibre in the concrete. Bridging fibre aligned with a crack are less effective than those inclined to it. Therefore, understanding the pull-out behaviour of misaligned fibre is a key factor to quantify and optimize the design of SFRC in the structural applications. In the laboratory a single oriented fibre embedded in a solid cylinder of concrete is subjected to a pull-out test where the axis of a tensile force is aligned with the axis of the cylinder. Based upon the observed behaviour this paper presents a new analytical bounding approach to capture the pull-out response of misaligned hooked-end steel fibre embedded in a concrete matrix. The analysis is based upon a transversely isotropic condition assumed for the plasticity that occurs in the cold drawn fibre. The model accounts for the influence of fibre diameter and the combined strengths of the steel and concrete. The model predictions have also been compared with other experimental results published in the literature. The results showed that the model can predict pull-out loads reasonably for different fibre orientations between bounds of failure derived from the strengths of the two constituents. A critical orientation is observed at maximum strength. Therein, an understanding of the pull-out behaviour of misaligned, hooked-end fibres is necessary to optimize the strength of concrete from this method of reinforcement.

The development of high complexity geometry parts is one of the main goals of the additive manufacturing technology. However, the failure of printed structures and the joining of different parts to create complex assemblies represents a real challenge in the research of efficient and sustainability techniques for the permanent assembly of polymers. Laser welding processes have been used as a single step method to join metals until years ago. Nowadays, the growing trend in the use of thermoplastics for additive manufacturing has led to the need to adapt this technique to materials with a very specific nature and more sensitive to thermal effects. Also, the possibility of transmitting the laser beam through transparent polymer layers allows to focus the energy supply on internal sections of the assembled components. In this research, an infrared laser marking system was used to join two different samples of polylactic acid manufactured by fused deposited modeling technology. In order to increase the effectiveness of the bonding process, a transparent and a dark sample have been used as assembly material, focusing the laser beam on the interface area of the two parts. By means of tensile tests, dimensional measurement and the use of optical microscopy techniques, a basis was established that links the supplied energy by laser to the joining performance.

In wild habitats, fruit dehiscence is a critical strategy for seed dispersal; however, in cultivated crops it is one of the major sources of yield loss. Therefore, indehiscence of fruits, pods, etc., was likely to be one of the first traits strongly selected in crop domestication. Even with the historical selection against dehiscence in early domesticates, it is a trait still targeted in many breeding programs, particularly in minor or underutilized crops. Here, we review of this trait in pulse (grain legume) crops, which are of growing importance as a source of protein in human and livestock diets, and which have received less attention than cereal crops and the model plant Arabidopsis thaliana. We specifically focus on the i) history of indehiscence in domestication across legumes, ii) structures and the mechanisms involved in shattering, iii) the molecular pathways underlying this important trait, iv) an overview of the extent of crop losses due to shattering, and the effects of environmental factors on shattering, and, v) efforts to reduce shattering in crops. While our focus is mainly pulse crops, we also included comparisons to crucifers and cereals because there is extensive research on shattering in these taxa.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

In this work, an analog front-end (AFE) circuit for Electrocardiogram (ECG) detection system has been designed, implemented, and investigated in an industry-standard Cadence simulation framework using advanced technology node of 45 nm. The AFE consists of an instrumentation amplifier, a Butterworth band-pass filter (with fifth-order low-pass and second-order high-pass sections), and a second-order notch filter- all are based on two-stage, Miller-compensated operational transconductance amplifiers (OTA). The OTAs have been designed employing the $g_m/I_D$ methodology. Both the pre-layout and post-layout simulation were carried out. The layout consumes an area of 0.0058 mm$^2$ without the resistors and capacitors. Analysis of various simulation results were carried out for the proposed AFE. The circuit demonstrates a post-layout bandwidth of 239 Hz with a variable gain between 44 to 58 dB, a notch depth of -56.4 dB at 50.1 Hz, a total harmonic distortion (THD) of -59.65 dB (less than 1\%), an input referred noise spectral density of $

Transforaminal lumbar interbody fusion (TLIF) is a commonly used technique for treating lumbar degenerative diseases. In this study, we developed a fully computer-supported pipeline to predict both the cage height and the degree of lumbar lordosis subtraction from the pelvic incidence (PI-LL) after TLIF surgery, utilizing preoperative X-ray images. The automated pipeline comprised two primary stages. First, a deep learning model was employed to extract essential features from X-ray images. Subsequently, five machine learning algorithms were trained to identify the optimal models to predict interbody cage height and postoperative PI-LL. LASSO regression and support vector regression demonstrated superior performance in predicting interbody cage height and postoperative PI-LL, respectively. For cage height prediction, the root mean square error (RMSE) was calculated as 1.01, and the model achieved the highest accuracy at a height of 12 mm, with exact prediction achieved in 54.43% (43/79) of cases. In most of the remaining cases, the prediction error of the model was within 1 mm. Additionally, the model demonstrated satisfactory performance in predicting PI-LL, with an RMSE of 5.19 and an accuracy of 0.81 for PI-LL stratification. In conclusion, our results indicate that machine learning models can reliably predict interbody cage height and postoperative PI-LL.

This paper presents a novel approach for indoor acoustic source localization using microphone arrays and based on a Convolutional Neural Network (CNN). The proposed solution is, to the best of our knowledge, the first published work in which the CNN is designed to directly estimate the three dimensional position of an acoustic source, using the raw audio signal as the input information avoiding the use of hand crafted audio features. Given the limited amount of available localization data, we propose in this paper a training strategy based on two steps. We first train our network using semi-synthetic data, generated from close talk speech recordings, and where we simulate the time delays and distortion suffered in the signal that propagates from the source to the array of microphones. We then fine tune this network using a small amount of real data. Our experimental results show that this strategy is able to produce networks that significantly improve existing localization methods based on SRP-PHAT strategies. In addition, our experiments show that our CNN method exhibits better resistance against varying gender of the speaker and different window sizes compared with the other methods.

Microplastics (plastic particles < 5 mm) are ubiquitous pollutants that pose the ability to carry microbiota, including pathogens. Microbial adhesion is usually a sign of pathogenicity, thus we investigated the adherent strains found on 4 mm nylon strips, which were ingested and excreted by wild fish specimens. Polymer analysis of the excreted samples shown no signs of degradation, nor have their controls, represented by the nylon strips submerged in the same water tanks. Both the ingested samples and controls presented pathogens in large numbers, revealing the fact that nylon microplastics can be physical carriers for pathogens in the aquatic environment.

Accurate determination of protein localization, levels, or protein-protein interactions is pivotal for the study of their function, and in situ protein labeling via homologous recombination has emerged as a critical tool in many organisms. While this approach has been refined in various model fungi, the study of protein function in most plant pathogens has predominantly relied on ex-situ or overexpression manipulations. To dissect the molecular mechanisms of development and infection for Verticillium dahliae, a formidable plant pathogen responsible for vascular wilt diseases, we have established a robust, homologous recombination-based in situ protein labeling strategy in this organism. Utilizing Agrobacterium tumefaciens-mediated transformation (ATMT), this methodology facilitates the precise tagging of specific proteins at their C-termini with epitopes, such as GFP and Flag, within the native context of V. dahliae. We demonstrate the efficacy of our approach through the in situ labeling of VdCf2 and VdDMM2, followed by subsequent confirmation via subcellular localization and protein-level analyses. Our findings confirm the applicability of homologous recombination for in situ protein labeling in V. dahliae and suggest its potential utility across a broad spectrum of filamentous fungi. This labeling method stands to significantly advance the field of functional genomics in plant pathogenic fungi, offering a versatile and powerful tool for the elucidation of protein function.

There is still an ambiguous opinion on oat regarding its safety for people with celiac disease (CD). Some studies have confirmed different content of oat immunoreactive epitopes in different cultivars while others explain the differences in consequence of cross-contamination with gluten-rich species or as ELISA cross-reactivity of oat homological epitopes with antibodies against wheat gliadin. Our study was based on a two-year mapping of oat immunoreactive epitopes in a set of 132 oat cultivars using the G12-based ELISA kit. Although repeated evaluation confirmed high interannual variability (RSD ≥ 30%) in approximately 2/3 of the cultivars, the permitted gluten content (20 mg kg-1) has not been exceeded except for contaminated cultivar Sirene. The polymorphism of purified avenins determined by SDS-PAGE revealed the occurrence of 2 bands around 30 kDa in oat cultivars with relatively high gluten content (12-16 mg kg-1) except for the cultivar Leo while this pattern occurred only in 50% oat cultivars with low gluten content. Quantification of gluten epitopes on purified avenin unit further revealed the three materials (Mojacar, Maris Oberon, SG-K 16370) with the lowest gluten content and presence of one band at 30 kDa. The band pattern at 30 kDa thus represents a promising breeding marker.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

In archaea, the interaction of HerA helicase and NurA nuclease is required for 3' end resection during DNA double-stranded break repair, and its disruption results in unfaithful DNA repair. Interactions transpire by the four conserved domains, including the N-terminal HAS domain (HerA-ATP synthase), which serves as a binding site for the exonuclease NurA. As a HerA hexamer between its two subunits, the conserved C-terminal brace extension functions as an adjacent brace. DBD serves as a location for DNA binding, which causes the DNA strands to be propelled into the HerA pocket to begin unwinding. The putative pore entrance is made up of four helix coils, which provide a suitable charged surface for guiding DNA into the pore. The crystal structure of the complex HerA-NurA allows for the identification of key residues for protein-protein interaction. This allows us to predict that most archaeal HerA orthologs will be able to interact with one another. Archaeal HerA is a homo-hexameric assembly featuring a DNA-binding domain that is conserved. It also features distinctive ATP and NurA binding domains. Following the structure and sequence conservation criteria, we find one HerA ortholog in Pyrobaculum calidifontis and multiple HerA paralogs, but the role of none is established yet.Interestingly, orthologous HerA is part of an Mre11-Rad50 gene neighborhood while paralogous HerA is not, which could be misleading. As a result, it sought to describe the criteria that may be used as a possible fingerprint for identifying orthologous genes, as well as the cloning procedures and tactics that would aid in the confirmation of the HerA helicase in P. calidifontis. Their confirmation is based on PCR cloning and characterization following HerA construct creation.

In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk aggravating factors for the development of chronic skin lesions. Stem cells regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of 3D bioprinted scaffolds. With this review we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, towards their relevance in the skin regeneration field.

Repair mortar is commonly used to rehabilitate reinforced concrete structures or components that exhibit a relatively high level of distresses. Yet, this repair mortar can be contaminated by salt from its service environment. This work employs a two-dimensional finite element model to investigate the transport behavior of ionic species in salt-contaminated and water-saturated repair mortar under an externally applied electric field. The model was experimentally validated and then utilized to evaluate the effectiveness of electrochemical chloride extraction (ECE) with or without electrical injection of corrosion inhibitor (EICI). In the case study, both the ECE alone and the ECE+EICI treatment was found effective in decontaminating the zone in front of the steel rebar. In both techniques, the magnitude of current density has a significant effect on removing chloride out of the mortar and increasing the pH of the pore solution near the rebar, whereas the treatment time any not have a significant effect under some scenarios. The injection of the organic corrosion inhibitor significantly slowed down the removal of chloride. Changes in the ionic distribution in the mortar were generally beneficial in reducing the corrosion risk of the steel rebar and thus extending the service life of the repair mortar.

DNA double-strand breakage is the most lethal damage to chromosomal DNA. It activates a series of cellular DNA damage response pathways, including DNA damage sensing, control of cell cycle arrest and apoptosis, and DNA repair. DNA damage response pathways are regulated by complex signaling machineries. Of the intracellular signaling cascades, diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to generate phosphatidic acid (PA). Because both DG and PA serve as second messengers, DGK activity induces a shift of signaling pathways from DG-mediated to PA-mediated cascades, thereby implicating DGK in the regulation of widely various functions. Reportedly, one member of the DGK family, DGKζ, is intimately involved in the regulation of stress responses through p53 and NF-κB. Stresses such as ischemia and infarction cause DGKζ downregulation. Experimental DGKζ depletion renders cells and mice vulnerable to various stressors such as chemotherapeutic agents and ionizing irradiation. Nevertheless, how DGKζ is involved in DNA repair, a critical event of DNA damage response for survival remains unknown. For this study, we examined how DGKζ depletion affects DNA repair mechanisms. We demonstrated that DGKζ depletion causes attenuation of Akt activation and DNA-PK protein expression upon DNA damage, which might engender downregulated BRCA1 protein synthesis and stability. Results suggest that DGKζ depletion attenuates BRCA1-mediated DNA repair machinery, thereby conferring vulnerability to DNA damage.

It is very difficult to repair large bone defects, especially when they have a complex shape. We have developed a new technique to make a desired copy of rabbit bones. A rabbit distal femur was scanned by computed tomography (CT), and a rectangular-shaped beta-tricalcium phosphate (β-TCP) block with 75% porosity was automatically machined using milling tools into a half-scale copy of the distal femur based on the CT data. The β-TCP block was seeded with bone morphogenetic protein-2 and bone marrow cells obtained from the femur and implanted on the periosteum of the femur. At 10 weeks after implantation, most of the β-TCP block had been replaced by bone and a complete copy of the distal femur was reconstructed. Our findings indicate that this technique will be useful in the clinical setting. We also report the representative clinical results of treatment with β-TCP graft in patients with bone defects since 1989.

Materials based on Mg2+-containing phosphates are gaining great relevance in the field of bone tissue repair via regenerative medicine methods. Magnesium ions, together with condensed phosphate ions, play a significant role in the process of bone remodeling, affecting the early stage of bone regeneration through active participation in the process of osteosynthesis. Here we pro-vide a comprehensive overview of the usage of biomaterials based on magnesium phosphate and magnesium calcium phosphate in bone reconstruction. The role of magnesium ions in angiogene-sis, an important process associated with osteogenesis, is considered. Finally, the biological properties of magnesium phosphates for bone regeneration are summarized. They show promis-ing results in terms of use as bone replacement material.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

Non-isocyanate polyurethane synthesis by non-Sn catalysis is an essential challenge toward green polyurethane synthesis. Bismuth compounds are attractive candidates due to their low cost, low toxicity, and availability to urethane chemistry. We applied various Bi catalysts to the self-polycondensation of a bishydroxyurethane monomer and found BiCl3 to be an excellent catalyst through optimization. The catalytic activity and price of BiCl3 are comparable to those of Bu2SnO, while its toxicity is significantly low. BiCl3 is, therefore, a promising alternative to Sn-based catalysts in non-isocyanate polyurethane synthesis.

Background: This study addresses the burgeoning impact of Large Language Models (LLMs) such as ChatGPT on the integrity of online examinations and seeks to demonstrate latent and advanced LLM reasoning capabilities. The research devises an iterative self-reflective strategy for invoking critical thinking and higher-order reasoning in LLMs based on multimodal exam questions using visuals and text. Methods: The proposed strategy was demonstrated and evaluated on real exam questions by subject experts and the performance of ChatGPT (GPT-4) with vision was estimated on an additional dataset of 600 text descriptions of multimodal exam questions, focusing on its response to complex, visual, and textual prompts. Results: The results indicate that latent multi-hop reasoning capabilities can be invoked using the proposed self-reflective strategy, which can effectively steer ChatGPT towards correct answers by integrating critical thinking from each modality into the final response. Meanwhile, ChatGPT demonstrated considerable proficiency in being able to answer multimodal exam questions across 12 subjects. Conclusions: This work challenges findings from recent studies which claim that existing LLMs are unable to reason on complex multimodal tasks, and therefore this study underscores the need for enhanced online exam security measures like proctoring software, that can mitigate the potential misuse of AI technologies in educational settings.

In the evolving landscape of pharmaceutical manufacturing, a comprehensive continuous production process is being crafted for small-scale active pharmaceutical ingredient production. This study focuses on continuous crystallization with separate nucleation and crystal growth units, as well as continuous downstream processing, encompassing filtration, washing, and drying until the formation of free-flowing particles. We introduce a novel continuous nucleator designed based on solubility data and produced via 3D printing, enabling a fast and precise small-scale manufacturing of a nucleator meeting the requirements for nucleation and for the further growth processes. The nucleator was evaluated with regard to its suitability for continuous long-term operation across various coupled crystallizers. As a practical application example it is connected to a slug flow crystallizer to enable high-quality continuous crystallization. Additionally, the full integration of downstream processes using the continuous vacuum screw filter to achieve free-flowing product particles is realized. Even under non-optimized process conditions, with the help of in-situ generation of nuclei free-flowing product particles were successfully obtained. This is particularly useful during drug development when no material is available for seed addition and quickly obtain product for further characterization.

The aim of this randomized controlled clinical trial was to compare the 2-year clinical performance of resin composite restorations placed at non-caries cervical lesions (NCCL) with one-step self-etch, total-etch, and selective enamel etch & self-etch adhesive techniques. Thirty-two patients received three resin composite restorations each at NCCLs (Tetric EvoCeram/Ivoclar/Vivadent), bonded with a total-etch adhesive agent (ExciTE F/Ivoclar/Vivadent) and a self-etch (AdheSE One F/Ivoclar/Vivadent) without and with selective enamel etching. All restorations were evaluated by two examiners at baseline, 6-, 12-, 18- and 24-months post-operation regarding retention, caries occurrence, marginal adaptation, and marginal staining. A logistic regression analysis with generalized estimating equations was used. After 2 years, the retention rate was 86,8% for total-etch, 92.26% for self-etch, and 93.63% for selective enamel etching & self-etch. No caries were detected during all the restorations. Concerning marginal adaptation, the clinically perfect restorations were 26.9% for the total-etch technique, 16% for self-etch, and 25,9% for selective enamel etch & self-etch. All three adhesive strategies provided restorations with no significant differences in the retention rate and the marginal adaptation, whereas the total etch yielded better performance for marginal staining. All the restorations were assessed as clinically acceptable after 2 years.

It has been more than three decades since the discovery of multifunctional factors, Non-POU Domain-Containing Octamer-Binding Protein, NonO and Splicing Factor, Proline-and Glutamine-Rich, SFPQ. Some of their functions, including their participations in transcriptional and posttranscriptional regulation as well as their contribution to paraspeckle subnuclear body organization have been well-documented. In this review, we focus on the roles of NonO and SFPQ in cell cycle with particular attention to their participation in nonhomologous end joining (NHEJ) and homologous recombination (HR) of DNA damage responses induced by irradiation. In these contexts, absence or malfunction of either or both lead to genome instability and ultimately to apoptosis, cellular senescence, and tumor development. This review also will shed light on NonO and SFPQ function in DNA/RNA/protein binding and their association with Ku heterodimer of the NHEJ pathway required for repair of DNA double-strand breaks (DSBs).

Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction. Docking was performed for unique lists of DNA repair proteins which predict OS for AML, cancers of the breast, lung, colon, and ovaries, GBM, melanoma, and renal papillary cancer. Results indicate hundreds of drug-like and lead-like ligands with best-pose binding energies less than -6 kcal/mol. Ligand solubility for the top 20 drug-like hits approached lower bounds, while lipophilicity was acceptable. Most ligands were also blood-brain barrier permeable with high intestinal absorption rates. While the majority of ligands lacked positive prediction for Herg channel blockage and Ames carcinogenicity, there was considerable variation for predicted fathead minnow, honey bee, and Tetrahymena pyriformis toxicity. The computational results suggest the potential for new targets and mechanisms of repair inhibition and can be directly employed for in vitro and in vivo confirmatory laboratory experiments to identify new targets of therapy for cancer survival.

The Easternmost Mediterranean is a junction zone between the largest Earth's lithospheric segments – Eurasian and African-Arabian, and a transition area from the ocean to the continent. The latest catastrophic earthquakes in eastern Turkey require their geodynamic understanding. The two most decisive events (with magnitude (M) = 7.8 and 7.7) were observed with an interval of 9 hours on February 06, 2023, followed by a whole series of about 10,000 significative aftershocks. These tragic events led to the death of more than 60 thousand people. The above values indicate the colossal tension created in the Earth's crust. The region where these strongest earthquakes occurred is a tectonically very complex junction zone of four tectonic plates: Eurasian, Arabian, African, and Anatolian. The joint movement of these plates (consisting, in turn, of tectonic elements of different ages) occurs at an average rate of 6–15 mm per year. However, after two marked powerful shocks and a series of aftershocks, some sectors of the Anatolian plate shifted to the southwest by more than 11 meters. What happened in eastern Turkey? The interaction of numerous factors complicates the tectonic–geodynamic characteristics of the region. Let us analyze what is the most influencing component. Our recent publications (Eppelbaum et al., 2020, 2021) indicated the presence of a giant, rotating quasi-ring structure below the Easternmost Mediterranean. The GPS vector map coinciding with the gravitational trend displays the counterclockwise rotation of this structure. A review of paleomagnetic data on the projection of the discovered structure into the Earth's surface confirms its mainly counterclockwise rotation. Analysis of the magnetic field ΔZ, geoid anomalies map, and seismic tomography data commonly prove the presence of this deep anomaly. The geodynamic and structural characteristics of the region and paleobiogeographic data are consistent with the proposed physical–geological model. A widespread analysis of tectonic, petrological, and mineralogical data implies a connection between the discovered deep structure and near-surface processes. An examination of numerous publications by different authors confirms the above phenomenon’s existence. A crucial for understanding the nature of the considered seismic stress is its location near the expressed bend of the Mesozoic terrane belt, where the Arabian Plate is deeply intruded into the Alpine-Himalayan belt. Thus, the rotation of this giant deep structure may accumulate the stress effect and be one of the causative reasons for the last catastrophic geodynamic events in Eastern Turkey.

Background: Since cytokine receptor like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. Methods: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno associated virus (AAV) or AAV containing CRLF1 was determined by morpholog-ical, histological and microCT analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were deter-mined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes us-ing real time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. Results: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondro-genic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and Cardiotrophin like Cytokine (CLC) stimulated catabolic events via STAT3 activation. Conclusion: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

We determined the levels of neutralizing antibodies against the SARS-CoV-2 ancestral strain, Delta and Omicron variants of concern (VOCs) in 125 healthcare workers, who received Coro-naVac as their primary vaccination and later received either a single ChAdOx1 or a combination of two consecutive boosters using either two ChAdOx1 doses or a ChAdOx1 or BNT162b2 as the primary and second boosters, respectively, or 2 doses of BNT162b2. The titers 12 weeks after primary vaccination were inadequate to neutralize the all strains. After a single ChAdOx1 boost-er, the levels of neutralization at Day 30 varied significantly, only a small proportion of partici-pants developing neutralizing titers against Omicron at Day 7 and 30. The two doses of ChA-dOx1 as the booster induced lowest activity. A combination ChAdOx1 and BNT162b2 induced greater neutralization than by two doses of ChAdOx1. Two doses of BNT162b2 as the booster had the maximal activity against Omicron VOC.

MicroRNAs (miRNA) exert regulatory actions via base-pairing with their binding sites on target mRNAs. Cooperative-binding, i.e., synergism, among binding sites on a mRNA is biochemically well-characterized. We studied whether this synergism is reflected in global relationship between miRNA-mediated regulatory activity and miRNA-binding-site count on the target mRNAs, i.e., leading to a non-linear relationship between the two. Recently, using our own and public datasets, we have enquired into miRNA regulatory actions: first, we analyzed the power-law distribution pattern of miRNA binding sites; second, strikingly, mRNAs for core miRNA regulatory apparatus proteins have extra-ordinarily high binding site counts, forming self-feedback-control loops; third, we revealed that tumor suppressor mRNAs generally have more sites than oncogene mRNAs; and fourth, we characterized enrichment of miRNA target mRNAs in translationally less-active polysomes relative to more-active polysomes. In these four studies, obvious correlation was observed qualitatively between the extent to which a mRNA is miRNA-regulated and its binding sites count. This paper summarizes the used datasets. We also re-analyzed the correlation by comparative linear and non-linear regression analyses. The results support a non-linear, instead of linear, relationship between the two parameters, conceivably a transcriptome-level reflection of cooperative-binding/synergism among miRNA binding sites on a target mRNA.

The state-of-the-art smart city has been calling for an economic but efficient energy management over large-scale network, especially for the electric power system. It is a critical issue to monitor, analyze and control electric loads of all users in system. In this paper, we employ the popular computer vision techniques of AI to design a non-intrusive load monitoring method for smart electric energy management. First of all, we utilize both signal transforms (including wavelet transform and discrete Fourier transform) and Gramian Angular Field (GAF) methods to map one-dimensional current signals onto two-dimensional color feature images. Second, we propose to recognize all electric loads from color feature images using a deep neural network with multi-scale feature extraction and attention mechanism. Third, we design our method as a cloud-based, non-intrusive monitoring of all users, thereby saving energy cost during electric power system control. Experimental results on both public and our private datasets have demonstrated our method achieves superior performances than its peers, and thus supports efficient energy management over large-scale Internet of Things.

Meat serves as a vital component of the human diet, offering a rich source of protein and essential trace elements. China stands as both a significant producer and consumer of meat on a global scale, leading the world in terms of total meat production and consumption. As the standard of living within the country continues to rise, there is a growing emphasis on the nutritional value and safety of meat consumption. The tenderness of meat is a critical factor influencing its overall quality. Traditionally, tenderness has been assessed through shear force testing, a method that is inherently destructive, inefficient, and results in considerable sample wastage. In light of these drawbacks, non-destructive testing techniques have emerged as a preferred alternative, promising greater accuracy, efficiency, and convenience without compromising the integrity of the samples. This paper delves into the application of five advanced non-destructive testing technologies in the realm of meat tenderness assessment. These include near-infrared spectroscopy, hyperspectral imaging, Raman spectroscopy, airflow optical fusion detection, and nuclear magnetic resonance detection. Each technology is scrutinized for its respective strengths and limitations, providing a comprehensive overview of their current utility and potential for future development. Moreover, the integration of these techniques with the latest advancements in artificial intelligence (AI) technology is explored. The fusion of AI with non-destructive testing offers a promising avenue for the development of more sophisticated, rapid, and intelligent systems for meat tenderness evaluation. This integration is anticipated to significantly enhance the efficiency and accuracy of quality assessment in the meat industry, ensuring a higher standard of safety and nutritional value for consumers. The paper concludes with a set of technical recommendations aimed at guiding the future direction of non-destructive, AI-enhanced meat tenderness detection, thereby contributing to the ongoing improvement of the meat industry in China and beyond.

Alterations in myelin, the protective and insulating sheath surrounding axons, affect brain function, as is evident in demyelinating diseases where the loss of myelin leads to cognitive and motor dysfunction. Recent evidence suggests that changes in myelination, including both hyper- and hypo-myelination, may also play a role in numerous neurological and psychiatric diseases. Protecting myelin and promoting remyelination is thus crucial for a wide range of disorders. Oligodendrocytes (OLs) are the cells that generate myelin, and oligodendrogenesis (OLgenesis), the creation of new OLs, continues throughout life and is necessary for myelin plasticity and remyelination. Understanding the regulation of OLgenesis and myelin plasticity within disease contexts is therefore critical for the development of novel therapeutic targets. In our companion manuscript [1], we review literature demonstrating that multiple hormone classes are involved in the regulation of OLgenesis under physiological conditions. The majority of hormones enhance OLgenesis, increasing oligodendrocyte precursor cell differentiation and inducing maturation and myelin production in OLs. Thus, hormonal treatments present a promising route to promote remyelination. Here, we review literature on hormonal regulation of OLgenesis within the context of disorders. We focus on steroid hormones, including glucocorticoids and sex hormones, peptide hormones such as insulin-like growth factor 1, and thyroid hormones. For each hormone, we describe whether they aid in OL survival, differentiation, or remyelination, and we discuss their mechanisms of action, if known. Several of these hormones have yielded promising results in both animal models and in human conditions; however, a better understanding of hormonal effects, interactions, and their mechanisms will ultimately lead to more targeted therapeutics for myelin repair.

This paper presents a theory on graph topological structure and graph coloring, proving that for any N-order graph structure (with a topological structure similar to ), the maximum number of colors required for coloring is less than or equal to . The Four Color Theorem is just one special case of this theory, with the maximum structure size for a four-color graph being a 4-order structure graph, hence requiring only a maximum of 4 colors for coloring.

Glucose is a simple sugar molecule. The sugar molecule is chemically symbolised as C6H12O6. This means that the glucose molecule contains 6 carbon atoms (C), 12 hydrogen atoms (H) and 6 oxygen atoms (O). In human blood, the molecule glucose circulates as blood sugar. Normally after eating or drinking, our body breaks down the sugars in food and uses them to obtain energy for our cells. To do this, our pancreas produces insulin. Insulin "pulls" sugar from the blood and puts it into the cells for use. If someone has diabetes, their pancreas can't produce enough insulin. As a result, the level of glucose in the blood rises. This can lead one to many potential complications, including blindness, disease, nerve damage, amputation, stroke, heart attack and damage to blood vessels etc. In this study, a non-invasive method for monitoring blood glucose has been developed and is therefore easily usable. The device developed can measure the glucose level continuously and eliminates the disadvantages of the invasive system. Near-IR sensors (optical sensors) were used to estimate the concentration of glucose in the blood; these sensors have a wavelength of 940 nm. The sensor is placed on the tip of the finger and the output of the optical sensor is then connected to the microcontroller at the analogue input. Another sensor used, but only to provide more medical information was the heartbeat sensor. After processing and regression analysis, the glucose level is predicted, and data is sent via the Bluetooth network to a developed APP. The results of the implemented device were compared with available invasive methods. The study consists of a hardware platform inserted into an armband and then a small black parallelepiped-shaped box in which the optical sensors are inserted. The hardware consists of a microcontroller, a Near-IR optical sensor, a heartbeat sensor and a Bluetooth module.

The effect of the heterogeneity in sex factor is considered in the Markovian manpower modeling model. The estimation of the transition probability matrix of the staff flow was done using the maximum likelihood method. The expected future durations of the individuals in the manpower system were obtained under the aggregated and disaggregated (male and female) staff flow as well as their variances. Test for the heterogeneity of the staff based on sex factor was performed and the result of the heterogeneity test shows that there is difference between the disaggregated staff flows. The computed entrant probabilities also indicate that the male group has higher probabilities of attaining higher grades than the female group.

(1) Background: Neurologic and musculoskeletal diseases represent a considerable portion of the underlying etiologies responsible for the widely prevalent symptoms of pain, weakens, numbness, and paresthesia. Because of the subjective and often nonspecific nature of these symptoms, different diagnostic modalities have been explored and utilized.; (2) Methods: Literature review; (3) Results: Nerve and muscle biopsy remains the gold standard for diagnosing many of the responsible neurological and musculoskeletal conditions. However, the need for invasive tissue sampling is diminishing as more investigations explore alternative diagnostic modalities. Because of this, it is important to explore the current role of neurosurgical intervention for nerve and muscle biopsies and its current relevance in the diagnostic landscape of neurological and musculoskeletal disorders. With consideration of the role of nerve and muscle biopsy, it is also important to explore innovations and emerging techniques for conducting these procedures. This review explores the indications and emerging techniques for neurological intervention for nerve and muscle biopsies; (4) Conclusions: The role of neurosurgical intervention for nerve and muscle biopsy remains relevant in diagnosing many neurological and musculoskeletal disorders. Biopsy is especially relevant as a supportive point of evidence for diagnosis in atypical cases. Additionally, emerging techniques have been explored to guide diagnostics and biopsy, conduct less invasive biopsies, and reduce risks of worsening neurologic function and other symptoms secondary to biopsy.

A great deal of studies have assessed the expression of noncoding RNAs (ncRNAs) as well as their relevant molecular functions and biological mechanisms in the individuals of alcohol dependence. Alcohol dependence is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is intricate and inadequately understood. There is considerable evidence demonstrating substantial links between multiple genetic factors and the development of alcohol dependence. Critical roles of ncRNAs have been emphasized in the pathophysiology of mental diseases including alcohol dependence. In the comprehension of ncRNAs action and their mechanisms of modification, they have emerged as therapeutic targets for a variety of psychiatric illness including alcohol dependence. Worth mentioning, dysregulated expression of ncRNAs has been regularly detected in individuals of alcohol dependence. An in-depth knowledge of roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a deeper comprehension of functional roles ncRNAs may make significant contributions to the precise diagnosis and/or actual treatment of alcohol dependence. Here in this review, we mostly focused on the up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in alcohol dependence, and then, presented their prospects for future research and therapeutic application with a novel concept of engram-system.

Acacia dealbata Link, named Mimosa in Portugal, is an invasive hardwood species with potential for construction use, but research is limited. The available stock of small-diameter juvenile wood (sjw) logs can help reduce this gap, but tangential cracking at log ends challenges fastener connections. This study evaluated different treatments to control and reduce end-face cracking in sjw logs during air drying, an economical and environmentally friendly procedure. Extreme two-thirds of sixteen Mimosa logs were subjected to two treatments: one with longitudinal kerfs 15 mm deep along the length (2 and 3 kerfs) and the other with a hollow in the centre up to half the length (16 mm and 30 mm diameters). Over 219 days of air drying and compared with the central part, kerfing treatments significantly reduced outer wood tangential cracking (p < 0.001), with the 3-kerf also reducing crack numbers (p < 0.05) but increasing significantly cracks near the pith (p < 0.01). The 30 mm central hollow significantly reduced central perforation cracking (p < 0.05). Results suggest that a combined treatment approach could help mitigate cracking, enhancing the suitability of wild Mimosa logs for construction use.

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder characterized by cognitive decline and neuronal loss, representing a most challenging health issue. We present a computational analysis of transcriptomic data of AD tissues vs. healthy controls, focused on elucidation of functional roles played by long non-coding RNAs (lncRNAs) throughout the AD progression. We first assembled our own lncRNA transcripts from the raw RNA-Seq data generated from 527 samples of dorsolateral prefrontal cortex, resulting in the identification of 31,574 novel lncRNA genes. Based on co-expression analyses between mRNAs and lncRNAs, a co-expression network is constructed. Maximal subnetworks with dense connections are identified as functional clusters. Pathway enrichment analyses are conducted over mRNAs and lncRNAs in each cluster, which serve as the basis for the inference of functional roles played by lncRNAs involved in each of the key steps in an AD development model that we have previously build based on transcriptomic data of protein-encoding genes. Detailed information is presented about the functional roles by lncRNAs in activities related to stress response, reprogrammed metabolism, cell-polarity, and development. Our analyses have also revealed that lncRNAs have discerning power in distinguishing between AD samples of each stage and healthy controls. This study represents the first of its kind.

Pit lakes can represent significant liabilities at mine closure. However, pit lakes also present opportunities to provide significant regional benefit and address residual closure risks of both their own and overall project closure, and even offset the environmental costs of mining by creating new end uses. Unfortunately, many pit lakes have continued to be abandoned without repurposing for an end use. We reviewed published pit lake repurposing case studies of abandoned mine pit lakes. We found beneficial end use type and outcome varied dependent upon climate and commodity; but equally important social and political dynamics that manifest as mining company commitments or regulatory requirements. Many end uses have been realized: passive and active recreation, nature conservation, fishery and aquaculture, drinking and industrial water storage, greenhouse carbon fixation, flood protection and waterway remediation, disposal of mine and other waste, mine water treatment and containment, and education and research. Common attributes and reasons that led to successful repurposing of abandoned pit lakes as beneficial end uses are discussed. Recommendations are given for all stages of mine closure planning to prevent pit lake abandonment and to achieve successful pit lake closure with beneficial end uses.