Parallel manipulators with multiple end-effectors bring us interesting advantages over conventional parallel manipulators such as improved manipulability, workspace and avoidance of singularities. In this work the kinematics of a five-bar planar parallel manipulator equipped with two end-effectors is approached by means of the theory of screws. As an intermediate step the displacement analysis of the robot is also investigated. The input-output equations of velocity and acceleration are systematically obtained by resorting to reciprocal-screw theory. In that regard the Klein form of the Lie algebra se(3) of the Euclidean group SE(3) plays a central role. In order to exemplify the method of kinematic analysis, a case study is included. Furthermore, the numerical results obtained by means of the theory of screws are confirmed with the aid of special software like ADAMS.^TM

Members of the genus Mycoplasma and related organisms impose a substantial burden of infectious diseases on humans and animals, but the last comprehensive review of mycoplasmal pathogenicity was published 20 years ago. Post-genomic analyses have now begun to support the discovery and detailed molecular biological characterization of a number of specific mycoplasmal virulence factors. This review covers three categories of defined mycoplasmal virulence effectors: 1) specific macromolecules including the superantigen MAM, the ADP-ribosylating CARDS toxin, sialidase, cytotoxic nucleases, cell-activating diacylated lipopeptides, and phosphocholine-containing glycoglycerolipids; 2) the small molecule effectors hydrogen peroxide, hydrogen sulfide, and ammonia; and 3) several putative mycoplasmal orthologs of virulence effectors documented in other bacteria. Understanding such effectors and their mechanisms of action at the molecular level connects the biology of the bacteria to direct effects on the host and host responses they elicit, and is expected to translate into new interventions for human and veterinary mycoplasmosis.

Scientists can use the Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 system, which is a powerful and flexible tool for changing the genome, to change only certain parts of the genome. This has helped researchers figure out how target genes work in biology and disease. CRISPR/Cas9 is made up of a sequence-specific CRISPR RNA (crRNA) set and a generic Cas9 nuclease. The crRNA set tells Cas9 where to cut DNA and cause double-strand breaks. In the next step of cellular DNA repair, insertions, deletions, and swaps are made at specific spots. For CRISPR/Cas9-mediated DNA cleavage to be specific, the target sequences must match the crRNA, and a protospacer nearby motif must be placed after the target sequences. In this article, we talk about how CRISPR/Cas9 works at the molecular level, what it can be used for, what it can't do, and what its future clinical treatment promise might be.

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.

Estimating parameters for multiple datasets can be time consuming, especially when the number of datasets is large. One solution is to sample from multiple datasets simultaneously using Bayesian methods such as adaptive multiple importance sampling (AMIS). Here we use the AMIS approach to fit a von Misses distribution to multiple datasets for wind trajectories derived from a Lagrangian Particle Dispersion Model driven from a 3D meteorological data. The primary objective is to characterise the uncertainties in wind trajectories in a form that can be used as inputs for predictive models of wind-dispersed insect pests and pathogens of agricultural crops for use in evaluating risk and in planning mitigation actions. Our results show that AMIS can significantly improve the efficiency of parameter inference for multiple datasets.

Abstract: The Willows, belonging to the genus Salix, encompass a vast array of species and hybrids, totaling between 330 to 500 species along with approximately 200 hybrids. These plants are found across continents such as Africa, North America, Europe, and Asia, exhibiting diverse forms ranging from trees to shrubs and prostrate plants. Traditionally, Willows have been utilized in folk medicine due to their rich reservoir of biologically active compounds, with salicin being a notable example, serving as a prodrug for salicylic acid.The chemical composition of Willows is highly diverse, with 322 secondary metabolites identified thus far. These include various classes such as flavonoids (94 types encompassing flavonols, flavones, flavanones, isoflavones, flavan-3-ols like catechins and procyanidins, chalcones, dihydrochalcone, anthocyanins, and dihydroflavonols), phenolic glycosides (76), organic acids (28), non-phenolic glycosides (17), sterols, and terpenes (17), simple phenolics (13), lignans (7), as well as volatiles and fatty acids (69). This rich chemical di-versity underpins the various pharmacological activities exhibited by Willows. The pharmacological properties attributed to Willows are extensive and include analgesic, an-ti-inflammatory, antioxidant, anticancer, cytotoxic, antidiabetic, antimicrobial, antiobesity, neuroprotective, and hepatoprotective effects. These properties make Willows a subject of con-siderable interest in the fields of medicine and pharmacology. In summary, Willows represent a valuable natural resource with a diverse chemical composition and a wide range of pharmacological activities. This study aimed to enhance our comprehension of the medicinal characteristics of willow bark extract, focusing on its antimicrobial properties. This investigation holds significance in validating the traditional usage of willow bark and investi-gating its potential utility in contemporary medicine.

MIMO (multiple-input multiple-output) radar provides much more flexibility than the traditional radar for its ability to realize far more observation channels than the actual number of T/R (transmit and receive) elements. Designing the array of MIMO imaging radar, the commonly used virtual array theory generally assumes that all elements are placed on the same line. However, due to the physical size of the antennas and coupling effect between T/R elements, a certain height difference between T/R arrays is essential, resulting in the defocusing of edge points of the scene. On the other hand, the virtual array theory implies far-field approximation, leading to inevitable high grating lobes in the imaging result of near-field edge points of the scene observed by common MIMO array. To tackle these problems, this paper derives the relationship between target’s PSF (point spread function) and pattern of T/R arrays, by which the design criterion of near-field imaging MIMO array is presented. Firstly, the proper height between T/R arrays is designed to focus the near-field edge points well. Secondly, the far-field array is modified to suppress the grating lobes in the near-field area. Finally, the validity of the proposed methods is verified by simulations and an experiment.

By repeated unloading and loading of the excavation dynamic and static loads, repeated train dynamic and static loads of multi-factors, the underpass tunnel, cross tunnel engineering influence area rock layer, the existing tunnel structure of the three constitutes a multifaceted structure, multi-factor interaction system. Existing tunnels into the prediction theory model of the new tunnel excavation process of dynamic and static loads, dynamic and static loads of existing tunnels are mostly analyzed individually, the results of synergistic analysis needs to be improved. Based on the theory of the current layer method, the paper comprehensively considers the stiffness of the existing tunnel, the stiffness of the new tunnel, the excavation method load and the existing tunnel load, coupled with Peck's empirical formula, the theoretical model of deformation prediction for excavation of a two-lane highway tunnel under the tunnel through the existing railroad is proposed, and verified and optimized by numerical calculations and monitoring data, which proves the applicability and reliability of the theoretical model in the similar strata and the project promotion.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

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.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

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.

Phytopathogenic oomycetes are known to infect a host plant successfully due to their ability to secrete a set of protein effectors. Of interest to many researchers are effectors with the N-terminal RxLR motif (Arginine-any amino acid-Leucine-Arginine). Owing to the genome sequencing, we can now comprehend the high level of diversity among oomycete effectors, and similarly, their conservation within and among species core RxLR effectors (CREs). Currently, there are a couple of putative CREs that have been identified in oomycetes. The functional characterization of these CREs proposes their virulence role with the potential of targeting central cellular processes that are conserved across diverse plant species. This could be harnessed in engineering plants for broad-spectrum and durable resistance.

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.

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.

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.

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).

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.

When dealing with limited sample sizes or missing values in time series data, achieving high accuracy in forecasting becomes challenging. This challenge is particularly common in wind energy forecasting, where many wind farms lack complete data. In this paper, we employ the widely-used ARIMA (Autoregressive Integrated Moving Average) model for time series forecasting. To address the difficulties posed by limited sample sizes and missing values, we adopt a unique approach by utilizing multiple ARIMA models for different datasets. A key distinction from other multiple models methods for time series forecasting lies in each model within our approach using its own dataset, making the fusion process more intricate. To overcome this, we incorporate neural networks and two techniques for model fusion: direct fusion with a learning mechanism and compensation for missing data through training. For each ARIMA model, we introduce a noise estimation method to circumvent the white noise assumptions inherent in ARIMA models. Finally, we apply these methods to wind energy prediction, and our experimental results showcase a significant enhancement in forecasting accuracy.

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.

Accurately estimating shrub biomass in arid and semi-arid regions is critical for understanding ecosystem productivity and carbon stocks at both local and global scales. However, capturing the shrub biomass accurately by satellite observations is challenging due to the short and sparse features of shrubs. In this study, we presented a framework to estimate shrub biomass at a 10m spatial resolution by integrating ground in-situ data, unmanned aerial vehicle (UAV), Sentinel-2, and Sentinel-1 observations. The pilot study was conducted in the Helan mountains of Ningxia province, China. First, the spatial distribution map of shrubland and other land cover types was generated in 2023. Then, a prediction model of shrub biomass was developed in a Random Forest Regression (RFR) approach driven by different predicted variable datasets based on in-situ measurements, UAV, and satellite images. Finally, the developed model was used to produce the biomass map of shrubland in 2023. The uncertainty was characterized by creating a standard deviation (SD) map using the Leave-One-Out Cross-Validation (LOOCV) method in the shrub biomass estimates. The resultant shrubland distribution map in 2023 has an F1 score of 0.92. The shrub biomass model driven by spectral bands and vegetation indices (R2= 0.62) demonstrated superior performance than that only driven by spectral bands (R2=0.33) or vegetation indices (R2=0.55). The uncertainty of the estimated biomass was lower than 4%, with the lowest values (<2%) happening in the high shrub coverage (>30%) and biomass production (>30kg/m2) regions. Furthermore, the findings show that the magnitude of shrub biomass was affected by the aridity and precipitation significantly in the study region. This study provides a workflow to accurately monitor the biomass of shrublands in a complicated environment based on remote sensing images from multi-platform observations.

Histone demethylases, enzymes responsible for removing methyl groups from histone proteins, have emerged as critical players in regulating gene expression and chromatin dynamics, thereby influencing various cellular processes. LSD2 and LSD1 have attracted considerable interest among these demethylases because of their associations with cancer. However, while LSD1 has received significant attention, LSD2 has not been recognized to the same extent. In this study, we conduct a comprehensive comparison between LSD2 and LSD1, with a focus on exploring LSD2's implications. While both share structural similarities, LSD2 possesses unique features. Functionally, LSD2 shows diverse roles, particularly in cancer, with tissue-dependent roles. Additionally, LSD2 extends beyond histone demethylation, impacting DNA methylation and DNA damage repair pathways. This study underscores the distinct roles of LSD2, providing insights into their contributions to cancer and other cellular processes.

A single mode waveguide grating coupler based on multiple Si-SiO₂ pairs onto Si substrate has been designed. Numerical analysis has been carried out to calculate optimum thickness of the layers of Si-SiO₂ that ensures the constructive interference between reflected waves and actual guided wave for high coupling efficiency. Based on the results, an optimal design is developed and modeled by using a 2-D finite difference time domain (2-D FDTD) simulator that dictates a coupling efficiency of as much as 78% (-1.07 dB) at the wavelength of 1550 nm, and a 1-dB bandwidth of 77 nm. The numerical method will be useful to calculate the optimum thicknesses of the layers for any reflector based grating coupler of different materials.

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.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

The Hippo pathway plays crucial roles in governing various biological processes during tumorigenesis and metastasis. Within this pathway, upstream signaling stimuli activate a core kinase cascade, involving MST1/2 and LATS1/2, which subsequently phosphorylates and inhibits the transcriptional co-activators YAP and its paralog TAZ. This inhibition modulates the transcriptional regulation of downstream target genes, impacting cell proliferation, migration, and death. Despite the acknowledged significance of protein kinases in the Hippo pathway, the regulatory influence of protein phosphatases remains largely unexplored. In this study, we conducted the first gain-of-functional screen for protein tyrosine phosphatases (PTPs) regulating the Hippo pathway. Utilizing a LATS kinase biosensor (LATS-BS), a YAP/TAZ activity reporter (STBS-Luc), and a comprehensive PTP library, we identified numerous novel PTPs that play regulatory roles in the Hippo pathway. Subsequent experiments validated PTPN12, a master regulator of oncogenic receptor tyrosine kinases (RTKs), as a previously unrecognized negative regulator of the Hippo pathway effectors, oncogenic YAP/TAZ, influencing breast cancer cell proliferation and migration. In summary, our findings offer valuable insights into the roles of PTPs in the Hippo signaling pathway, significantly contributing to our understanding of breast cancer bi-ology and potential therapeutic strategies.

This paper is aimed at studying the temporal evolution of the surface displacements occurred over the past few years in the ocean-reclaimed platforms of the Shanghai megacity (China), which are mainly ascribable to consolidation processes of large dredger fills and alluvial deposits. With respect to previous analyses carried out over the same area, this work provides a joint multi-platform differential interferometry synthetic aperture radar (DInSAR) analysis, based on the application of the advanced Small BAseline Subset (SBAS) algorithm. This led us to retrieve long-term deformation time-series that are helpful for a better understanding of the on-going deformation phenomena. To this aim, we have exploited two sequences of SAR data collected by the ASAR/ENVISAT and by the COSMO-SkyMed (CSK) sensors, respectively, spanning the whole time period from 2007 to 2016. Unfortunately, the large time gap (of about three years) existing between the available ASAR/ENVISAT and CSK datasets gave rise to additional difficulties for their combination. Nevertheless, this problem has been faced by benefiting from the knowledge of a time-dependent model describing the temporal evolution of the expected deformations affecting the Shanghai ocean-reclaimed platforms.

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.

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.

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.

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.

This article proposes an interferometer which should in principle split further an initially split beam to yield new sets of beams, effectively multiplying the number of beams that can be subjected to detectable interference. It can be considered a modification to the Michelson interferometer that introduces additional arrays of beam splitters, mirrors and detectors. It is expected of the interferometer to provide us with a set or sets of data holding details of phase changes in multiple interference patterns detectable by multiple detectors, enabling comparative analysis of data for multiple interference patterns recorded from a single measurement or activity. The number of multiplied beams possible is not limited, as it only depends on the specific amount of beam splitters required for certain experiments and practicals. The interference of multiple beams may improve sensitivity and detection for instrumentation purposes. The use of multiplied beam interferometry may also extend to quantum computation, particularly in linear optical quantum computation scheme as it enable production of multiple coherent beams which may exhibit properties of entanglement, making it suitable for developing optical multi-qubit systems.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

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.

A novel determination method using flow-through cartridge purification and ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was developed for the identification and quantification of 30 mycotoxins (aflatoxin B1, B2, G1, G2, sterigmatocysin, T-2 toxin, diacetoxyscirpenol, roquefortine C, methylergonovine, ergocornine, lysergol, enniatin A, enniatin A1, enniatin B, enniatin B1, beauvericin, deoxynivalenol, 3-acetylDeoxynivalenol, 15-acetylDeoxynivalenol, patulin, verruculogen, neosolaniol, gliotoxin, HT-2 toxin, wortmannin, zearalenone, α-zearalenol, β-zearalenol, α-zearalanol, and β-zearalanol) in feedstuffs. Mycotoxins were extracted from sample by 0.1% formic acid aqueous solution/acetonitrile (16/84 v/v), then purified by a Cleanert® MC clean-up column. As a result, the pigments and other matrices were efficient removed from the sample extract solution. The purified eluate was collected, then evaporated and redissolved by 0.1% formic acid aqueous solution/acetonitrile (70:30 v/v) for UPLC-MS/MS detection. A BEH Shield RP18 chromatographic column was employed for separation of 30 mycotoxins in a total of 14 min. Multiple-reaction monitoring (MRM) mode was applied for qualitative and quantitative analysis, and matrix calibration curves obtained with the external-standard method was used for quantitation of target analytes. Under optimized conditions, the linearity range was from 2 to 1000 ng/g, and the limit of quantification of the developed method was from 2 to 50 ng/g. The recoveries of 30 mycotoxins spiked in urine samples were from 72.0% to 118.5%, and the relative standard deviation was below 20%. The method was also well approved by certified reference sample, and applied on the real feedstuff samples testing successfully.

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.

Background: Disparity in adult mortality (AM) with reference to social dynamics and health care has not been sufficiently examined. This study aimed to identify the gap in the understanding of AM in relation to religion, political stability, economic level, and universal health coverage (UHC). Methods: A cross-national study was performed with different sources of data, using the administrative record linkage theory. We created a new data set using data from the 2013 World Bank data catalogue by region, The Economist (Political instability index 2013), Stuckler David et al. (Universal health coverage, 2010), and religious categories of all UN country members. Descriptive statistics, a t-test, an ANOVA followed by a post hoc test, and a linear regression were used where applicable. Result: The average AM rate for males and females was 0.20 ± 0.10 and 0.14 ± 0.10, respectively. AM was significantly higher in economically weak countries, countries with political instability, countries with traditional religion, without achievement of UHC, and Sub-Saharan Africa (p<0.01). There was high disparity of AM between countries with and without UHC (F = male: 61.89, female: 51.85, p<0.001) and between groups with low and high income (F = male: 36.33, female: 42.39, p<0.001). UHC and political stability would significantly reduce AMR by > 0.41 in both sexes and high economic status would reduce male AMR by 0.44, and female AMR by 0.70, in relation to countries without UHC, with political instability, and low economic status. Conclusions: Disparities in AM can be reduced after the achievement of UHC and economically productive activities for those adults affected by conflict and political unrest.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgAN causes end-stage kidney disease (ESKD) in 20–40% of all cases. The activation of the complement system by pathological circulating IgAs, which is often associated with low serum C3 levels (LowC3), seems to play a crucial role. Previous studies have shown an association between histological evidence of TMA, which is the result of alternative complement activation, and poor outcome. However, it is not known to what extent the decrease in serum C3 levels reflects ongoing TMA injury. Our study aimed at assessing the association of LowC3 and ESKD and whether this association reflects ongoing TMA. We enrolled all patients with biopsy-proven IgAN and followed-up patients until last visit, ESKD or death. Of the 56 patients included in the study, 12 (21%) presented low serum C3 (LowC3) at the time of renal biopsy. TMA was significantly more frequent in the LowC3 group [7/12 (58%) vs 9/44 (20%), p=0.02]. After adjusting for potential confounders, LowC3 was strongly associated with an increased hazard of ESKD (hazard ratio [HR]: 5.84 [95%CI: 1.69,20.15; P=0.005). The association was not affected by adjusting for TMA. The estimated overall proportion of the relation between C3 and ESKD mediated by TMA was low and not statistically significant. Our study provides evidence that C3 hypocomplementemia is associated with an increased risk of ESKD with mechanisms that are largely independent from TMA.

In large-capacity energy storage systems, instructions are decomposed typically using an equalized power distribution strategy, where clusters/modules operate at the same power and durations. When dispatching shifts from stable single conditions to intricate coupled conditions, this distribution strategy inevitably results in increased inconsistency and hastened system aging. This paper presents a novel differentiated power distribution strategy comprising three control variables: the rotation status, the operating boundaries for both Depth of Discharge (DOD) and C-rates (C) within a control period. The proposed strategy integrates an aging cost prediction model developed to express the mapping relationship between these control variables and aging costs. Additionally, it incorporates the multi-colony particle swarm optimization (Mc-PSO) algorithm into the optimization model to minimize aging costs. The aging cost prediction model consists of three functions: predicting health features (HFs) based on the cumulative charge/discharge throughput quantity and operating boundaries, characterizing HFs as comprehensive scores, and calculating aging costs using both comprehensive scores and residual equipment value. Further, we elaborated on the engineering application process for the proposed control strategy. In the simulation scenarios, this strategy prolonged the service life by 14.62%, reduced the overall aging cost by 6.61%, and improved module consistency by 21.98%, compared with the traditional equalized distribution strategy. In summary, the proposed strategy proves effective in elongating service life, reducing overall aging costs, and increasing the benefit of energy storage systems in particular application scenarios.

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.

Patients with end stage liver disease (ESLD) undergoing liver transplantation are prone to thromboses both while on the waiting list or in the perioperative period. This hypercoagulability is associated with significant endothelial dysfunction (ED) due to nitric oxide dysregulation. ED in combination with increased thrombin generation are the main factors responsible for this hypercoagulability. Sepsis itself can significantly change the coagulation profile, but in combination with ESLD, sepsis, and septic shock is responsible for very complex changes in the patients coagulation making both assessment and management of coagulation in patients with ESLD very challenging. Viscoelastic testing (VET) is a preferred method of coagulation management in patients with cirrhosis because, as with standard laboratory testing, VET can assess the entire coagulation system including the interaction between both pro- and anticoagulants and platelets.

The cyclic universe theory is a model of cosmic evolution according to which the universe undergoes endless cycles of expansion and cooling, each beginning with a big bang and ending in a big crunch. In this paper, the researcher finds a unique property of Space-time, this particular and marvelous nature of space shows us that space can shrink, expand, and stretch. This property of space is caused the size of the Universe changing over time: growing or shrinking. The observed accelerated expansion, which relates the stretching of Shrunk space for the new theory, is derived. This model is based on three underlying notions: First, the Big Bang was not the beginning of Space-time, but rather at the very beginning fraction of a second there was an infinite force of infinite Shrunk space in the cosmic singularity, that force gave rise to the big bang and caused the rapidly growing of space-time, and all other forms of energy are transformed into matter and radiation and a new period of expansion and cooling begins. Second, there was a previous phase leading up to it, with multiple cycles of contraction and expansion that repeat indefinitely. Third, the two principal long-range forces are the gravitational force and the repulsive force generated by shrunk space. They are the two most fundamental quantities in the universe that govern cosmic evolution. They may provide the clockwork mechanism that operates our eternal cyclic universe. The space will not continue to expand forever, no need however, for dark energy and dark matter. This model of Space-time and its unique properties enables us to describe a sequence of events from the Big Bang to the Big Crunch.

This paper presents the validation of the End Point Rate (EPR) tool for QGIS (EPR4Q), a tool built-in QGIS Graphical Modeler to calculate the shoreline change by End Point Rate method. The EPR4Q tries to fill the gap of user-friendly and free open-source tool for shoreline analysis in Geographic Information System environment, since the most used software - Digital Shoreline Analysis System (DSAS) - although is a free extension, is suited for commercial software. Besides, the best free open-source option to calculate EPR called Analyzing Moving Boundaries Using R (AMBUR), since it is a robust and powerful tool, the complexity and heavy processes can restrict the accessibility and simple usage. The validation methodology consists of applying the EPR4Q, DSAS, and AMBUR on different examples of shorelines found in nature, extracted from the U.S. Geological Survey Open-File. The obtained results of each tool were compared with Pearson correlation coefficient. The validation results indicate that the EPR4Q tool created acquired high correlation values with DSAS and AMBUR, reaching a coefficient of 0.98 to 1.00 on linear, extensive, and non-extensive shorelines, guarantying that the EPR4Q tool is ready to be freely used by the academic, scientific, engineering, and coastal managers communities worldwide.

Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties, including anti-inflammatory, antiviral and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures, but also new synthetic routes developed during the last years as well as promising therapeutic applications.

After UV excitation, gas phase thymine returns to ground state in 5 to 7 ps, showing multiple time constants. There is no consensus on the assignment of these processes, with a dispute between models claiming that thymine is trapped either in the first (S1) or in the second (S2) excited states. In the present study, nonadiabatic dynamics simulation of thymine is performed on the basis of ADC(2) surfaces, to understand the role of dynamic electron correlation on the deactivation pathways. The results show that trapping in S2 is strongly reduced in comparison to previous simulations considering only non-dynamic electron correlation on CASSCF surfaces. The reason for the difference is traced back to the energetic cost for formation of a CO p bond in S2.

Dielectric elastomer actuators (DEAs) offer robust, high energy density solutions for soft robotics. The proposed end effector consists of three spring roll configuration DEAs, each acting as a robotic finger, using a 3M VHB-F9473PC adhesive membrane. The lateral force, bending angle and response time of the actuator are measured experimentally and compared with the predictions of an analytical model. The cylindrical actuator measures 70 mm in length and 15 mm in diameter and achieved a lateral force of 30 mN, a bending angle of 6.8 ° and a response time of ≈ 1 s. Spring roll configuration DEAs are shown to reduce the effects of viscoelasticity seen in the membrane, making the actuator more controllable at higher voltages. The dielectric constant of the membrane is shown to be a limiting factor of actuation, with a decrease in dielectric constant resulting in larger actuation. The end effector successfully gripped numerous light objects for extended periods, showing the applicability of spring roll DEAs for soft end effectors.

A large number of novel treatments for myeloma have been developed and approved, however alkylating drugs continue to be part of standard regimens, additionally, novel alkylators are currently being developed. We performed a non-systematized literary search for relevant papers and communications at large conferences, as well as exploiting the authors knowledge of the field to review the history, current use and novel concepts around traditional alkylators cyclophosphamide, bendamustine and melphalan and current data on the newly developed pro-drug melflufen. Even in the era of targeted treatment and personalized medicine, alkylating drugs continue to be part of standard-of-care in myeloma, and new alkylators are coming to the market.

This paper discusses a MEMS switch that can be fabricated using low temperature (<100^oC) deposition and patterning techniques suitable for the back-end-of-the-line integration with CMOS. The resulting cross-bar switches can be used for electrostatic discharge protection, FPGA implementation, chip security assessment and lock-down, and circuit block power management. We discuss platinum and iron switch with turn-on voltages of ~ 1.8 V. In the case of the iron switches, we also show that they can be magnetized to have “memory” and stay on when turned on. Platinum switch cycling of up to 1000 times did not show any changes in their turn-on voltage and their contact resistance was unchanged. The 10-100 nm switch airgaps were formed using low temperature sputtered sacrificial polysilicon and XeF₂ etching. XeF₂ does not attack any of the metals used in CMOS enabling fabrication of cross-bar switches with any of these metals. Once activated, it takes ∿ 6 to mechanically turn on the switch that can be decreased to ~1 ns by optimizing the device structure. Interestingly, the nm-scale gaps can be used as spark gap as a fast plasma switch to discharge first followed by the activation of the MEMS switch.

This paper presents a study of the 2D roughness profiles on a flat surface generated on a steel work piece, by ball nose end milling, with linear equidistant tool paths (pick-intervals). The milled surface exploration with a surface roughness tester (on pick and feed directions) produces usually 2D roughness profiles having periodical evolutions. These evolutions can be seen as time-dependent signals, describable as a sum of sinusoidal components (the wavelength of each component being regarded as a period). In order to detect a well approximated description of these components, two appropriate signal processing techniques are used in this work: first technique provides a direct mathematical (analytical) description and is based on computer aided curve (signal) fitting (more accurate), the second technique (providing an indirect and incomplete description) is based on the spectrum generated by fast Fourier transform (less accurate). This study can be seen as a way for a better understanding the interaction between the tool and the work piece or to achieve a mathematical description of the machined surface microgeometry in terms of roughness (e. g. its description being a collection of closely spaced 2D roughness profiles).

MAACS is a software architecture which layers multiple standard cipher algorithms together to increase the overall strength of the encrypted data stream, without modifying the standard algorithms, which have been heavily vetted from a cryptanalysis perspective and are already widely deployed. This layering technique makes the combination of algorithms significantly more resistant to traditional cryptanalysis attacks, while also addressing increased concerns over future quantum computing attacks against these algorithms. For example, concerns over published attacks against 256-bit AES and potential future attacks emanating from Grover’s algorithm and other unknowns in the quantum computing era are explored. Several approaches for evolving AES are considered. MAACS uses a concept termed "aperiodic modulation", whereby of a set of cryptographic algorithms are modified by an- other, independent software algorithm in an unpredictable, pseudo-random manner. In the MAACS reference architecture, a 256-bit ChaCha20 cryptographically secure pseudorandom number generator (CSPRNG) drives an aperiodic modulator that orchestrates encryption/decryption processes multiplexed across eight parallel 128-bit AES instances, yielding a cryptosystem with a composite strength of 1,376 bits or more in larger configurations.

To study the coupling mechanism and dynamic response of the end-face movable gear trans-mission system under complex excitation, a specific configuration of end-meshing movable gear reduction mechanism was used to achieve predetermined rigid thrust transmission and mis-matched gear meshing functions, which solved the inherent defects of traditional harmonic gear mechanism thin-wall flexible wheel easy to be damaged by fatigue. Considering the phenomenon of elastic deformation of live teeth accompanied by significant changes in meshing characteristics in the transmission process of end-meshing harmonic reducer, the influence of dynamic meshing parameters, live tooth deformation, time-varying stiffness of tooth meshing, and time-varying backlash on nonlinear dynamic performance was explored, as well as the mechanism of mul-ti-parameter coupling on transmission performance. The nonlinear dynamics model of the end-meshing harmonic reducer is established to solve the chattering prediction problem. Finally, a comprehensive test bed for the transmission system of harmonic reducer with meshing type with adjustable characteristic end was built to verify the correctness of the theoretical model and provide the theoretical and technical basis for exploring the optimal parameter selection of pas-sive vibration suppression problem.

The standard model of cosmology assumes that our Universe began 14 Gyrs (billion years) ago with a hot Big Bang expansion out of nothing. It can explain a vast range of different astrophysical data from a handful of free cosmological parameters. However successful this model is, we have no direct evidence or fundamental understanding of some key assumptions: low entropy start, Inflation, Dark Matter and Dark Energy. Here we present a simpler and more physical explanation for the same observations that do not require such assumptions or new laws of Physics. It is based on the evidence that we live inside a Black Hole (BH) of mass $ M \simeq 5 \times 10^{22} M_{\odot}$, which we observed as cosmic acceleration. How did the Big Bang end up inside such a BH? We propose that 25 Gyrs ago, a very low density dust cloud collapsed and form such BH. As there was no pressure support, the collapse continued inside until it reached neutron energy densities (GeV). Causal regions of solar mass size rebound by neutron degeneracy, like a supernovae, producing the Big Bang expansion and compact dark matter remnants. During collapse, perturbations exit the horizon to re-enter during expansion, given rise to the observed universe. We review the evidence for such BH Universe.

Background. Wnt-pathway proteins play a vital role in kidney development and defects in the Wnt-pathway are associated with kidney disorders. However, the knowledge on the role of Wnt/β-catenin pathway proteins in end-stage renal disease (ESRD) is limited.Aim of the study. To delineate the association of ESRD and Wnt-proteins including the agonistR-spondin 1, the transducer β-catenin and the antagonists Dickkopf-related protein 1 (DKK1) and sclerostin.Methods. Serum Wnt-pathway proteins levels were measured by ELISA, while other biochemicals were measured spectrophotometrically in 60 ESRD patients and 30 normal controls.Results. DKK1 and sclerostin were significantly higher in ESRD than in controls, and β-catenin and the catenin + R-Sponin-1 / DKK1 + sclerostin ratio, reflecting the ratio of agonist and transducer on antagonists (AT/ANTA), were significantly lower in ESRD. Logistic regression analysis showed that ESRD was significantly predicted by increased levels of DDK1 and sclerostin and lowered β-catenin (p<0.001). eGFR was significantly associated with DKK1 and sclerostin (inversely), β-catenin (positively) and the AT/ANTA ratio (r=0.468, p<0.001). DKK1 levels were significantly and positively correlated with urea, creatinine, and copper. DKK1 and sclerostin were inversely associated with hemoglobin and packet cell volume. Catenin was significantly negatively associated with copper, urea and creatinine.Conclusion. Wnt/β-catenin pathway proteins show significant alterations in ESRD, indicating significantly increased levels of antagonists and, therefore, attenuated Wnt/β-catenin pathway activity. The latter is associated with lowered eGFR and increased serum copper levels. Wnt/β-catenin pathway proteins are possible drug targets to treat ESRD or its consequences.

Euler sums are alternating (or level two) extension of multiple zeta values (MZVs). Kaneko and Tsumura initiated the study of multiple T-values (MTVs), another level two generalization, by restricting the summation indices in the definition of MZVs to a fixed parity pattern. In this paper, we shall study finite MTVs and their alternating versions which are level two and level four variations of finite MZVs, respectively. We conjecture that all finite MZVs are in the Q-span of finite MTVs which in turn apparently lie in the span of finite Euler sums, and the inclusions are both proper. We shall first provide some structural results for Euler sums of small weights, guided by the author's previous conjecture that the finite Euler sum space of weight w is isomorphic to a quotient Euler sum space of weight w. Then, by utilizing some well-known properties of the classical alternating MTVs, we shall derive a few important Q-linear relations among the finite alternating MTVs, including the reversal, linear shuffle and sum relations. We then compute the upper bound for the dimension of the Q-span of weight w finite (alternating) MTVs for w<9, both rigorously using the newly discovered relations and numerically aided by computers.

This is the second of a series of two papers comparing the end of life issues in human and veterinary medicine. We outline the main differences between human and animal patients such as patient communication, finance and ‘conflicts of interest’ between animal, owner and veterinarian. We discuss striking similarities between human and veterinary issues such as assessing quality of life and the primary role of the attending veterinarian or doctor being the welfare and care of the patient. This paper takes the form of an ethical argument in favour of allowing euthanasia in human medicine, by providing insights into end of life issues for humans from an independent veterinary perspective. Veterinary surgeons are well trained in the ethics of euthanasia and put it to good use in the best interest of their animal patients. Doctors in the UK are limited and unwilling to put forward a case for the option of euthanasia for those patients who face a slow and agonizing death. With advances in medical science being able to significantly prolong the dying process, autonomy for the patient demands a review of the law regarding patient choice in the UK.

Active front-end (AFE) rectifiers have been becoming widely employed in power systems to achieve unity power factor and harmonic mitigations. The typical modeling approaches applied for AFE rectifiers in the literature mostly relied on two baselines named the detailed model and the time average model. The former approach deals with the switching element model (SEM) leads to significant harmonics in currents with distorted waveforms. The latter approach uses the average-value model (AVM) to overcome the currents’ harmonics as well as provide fast responses. However, even the AVM baseline has contained problems during the starting stage (lack of control signals) and over the dead-time periods which causes serious issues in the implementation process. This paper presents an improved dynamic AVM for AFE rectifiers by precisely considering the issues mentioned above along with the practical starting procedure and desirable initialization. The studied AFE rectifier is developed using the voltage-oriented control (VOC) technique based on the different modeling methodologies including SEM, Conventional AVM, and the proposed AVM. The performance of all models is analyzed and compared using simulation results with MATLAB/Simulink R2023a Function blocks for all the algorithm parts and SimScape elements for the electrical circuit model. The simulation results illustrate that the performance of the proposed AVM approach can closely resemble the behavior of the SEM baseline with low harmonic distortion.

Background: Once a widely used analgesic in the United States (US), meperidine offered an alternative to other opioids as a pain reliever. However, within the last two decades, meperidine has gone from a drug to be utilized only when patients exhibit atypical reactions to opioids (e.g., morphine and hydromorphone) to being taken off the World Health Organization List of Essential Medications and receiving strong recommendations for the overall avoidance. The aim of this study was to identify changes in meperidine distribution in the US and regional disparities as reported to the Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (DEA ARCOS) and Medicaid. Methods: Data related to the meperidine distribution was obtained through ARCOS (2001 –2021) and Medicaid public use files (2016 –2021). Heat maps were used to visualize regional disparities in distribution by state. States outside a 95% confidence interval were statistically significant. Results: Meperidine distribution between 2001 and 2021 decreased by 97.4% (R=.-97, P &lt; .0001). There was a 34-fold state-level difference in meperidine distribution between Arkansas (16.8 mg/10 persons) and Connecticut (0.5 mg/ 10 persons) in 2020. Meperidine distribution in 2020 was elevated in Arkansas, Mississippi, and Alabama. In 2021, Meperidine distribution was highest in Arkansas ( 1.67 /10 persons) and lowest in Connecticut (0.08 /10 persons). Total prescriptions of meperidine as reported by Medicaid decreased by 73.8% (R= -0.67, P = 0.045) between 2016 and 2021. Conclusion: We observed a decrease in the overall distribution of meperidine in the past two decades with similar recent declines in prescribing to Medicaid enrollees. The shortage of some parenteral formulations is an important contributor to these declines. This data may reflect plans to phase out the use of this opioid, especially in the many situations where preferred opioids are available.

Health information and communication are key elements that allow patients and family members to make decisions about end-of-life process and guarantee a death with dignity. Objective: To understand carers’ experiences regarding health information and communication during the illness and death of family members. Methods: This qualitative study was conducted in Andalusia based on the paradigm of hermeneutic phenomenology. Participants were carers who had accompanied a family member at the end of life for over 2 months and less than 2 years. Five nominal groups and 5 discussion groups were established, and 41 in-depth interviews with 123 participants were conducted. Atlas.ti 7.0 software was used to analyse the discourses. Results: Four dimensions of the dying process emerged: differences in carers’ perceptions of information and communication, a conspiracy of silence, consequences of the absence or presence of information, and the need for a culture change. Conclusions: Poor management of health information and communication at the end of life suffering and discomfort patients and their families. The culture of denying and avoiding death is still present today. A change in education about death would better enable health professionals to care for patients at the end of life.

The lytic bone disease is a hallmark of multiple myeloma, being present in about 80% of patients with newly diagnosed MM, and in more during the disease course. The myeloma associated bone disease (MBD) severely affects the morbidity and quality of life of the patients. MBD defines treatment demanding MM. In recent years, knowledge of the underlying pathophysiology has increased, and novel imaging technologies, medical and non-pharmaceutical treatments have improved. In this review, we highlight the major achievements in understanding, diagnosing and treating MBD. For diagnosing MBD, low-dose whole-body CT is now recommended over conventional skeletal survey, but also more advanced functional imaging modalities, such as diffusion-weighted MRI and PET/CT are increasingly important in the assessment and monitoring of MBD. Bisphosphonates have, for many years, played a key role in management of MBD, but denosumab is now an alternative to bisphosphonates, especially in patients with renal impairment. Radiotherapy is used for uncontrolled pain, for impeding fractures and in treatment of impeding or symptomatic spinal cord compression. Cement augmentation has been shown to reduce pain from vertebral compression fractures. Cautious exercise programs are safe and feasible and may have the potential to improve the status of patients with MM.

This study innovatively assesses the Mun River flow components in Thailand, integrating Artificial Neural Networks (ANN) and Isotopic (18O) End-Member Mixing Analysis (IEMMA). It quantifies the contributions of the Upper Mun River (UMR) and Chi River (CR) to the overall flow, revealing a discrepancy in their estimated contributions. ANN predicts the UMR and CR contribute approximately 70.1% and 29.5% respectively, while IEMMA indicates a more pronounced disparity with 84% from UMR and 16% from CR. This divergence highlights the distinct perspectives of ANN, focusing on hydrological data patterns, and IEMMA, emphasizing isotopic signatures. Despite discrepancies, both methods validate UMR as a significant contributor to the overall flow, highlighting their utility in hydrological research. The findings underscore the complexity of river systems and advocate for an integrated approach of river flow analysis for a comprehensive understanding, crucial for effective water resource management and planning.

Background. There is limited evidence on the relationship between chronic kidney disease (CKD) and frailty in older people in Vietnam. This study aimed to examine the prevalence of frailty and its impact on mortality in older patients with end-stage renal disease. Method. This is a prospective, observational study at two large Dialysis Centres in Vietnam from November 2020 to June 2021. Consecutive older patients diagnosed with end-stage renal disease and on dialysis were recruited. Participants’ frailty status was defined by the Clinical Frailty Scale (CFS). The study outcome was all-cause mortality at 6th month. Results. A total of 175 participants were recruited (mean age 72.4 years, 58.9% female). Using the cut-point of CFS ≥4, 87.4% of the participants were frail. Mortality at 6th month was 14.9%, 31.9% in participants with CFS ≥7, 12.8% in participants with CFS=6, 7.5% in participants with CFS from 4 to 5, and 4.5% in participants with CFS ≤3 (p=0.001). Cox regression analysis showed that compared to the non-frail participants, the probability of death over 6 months was nearly 2-fold higher in the mildly frail, 3-fold higher in the moderately frail, and 9-fold higher in the severely frail participants. Conclusion. This study demonstrated a very high prevalence of frailty in older patients with end-stage renal disease and dialysis and the significant impact of frailty severity on mortality. Healthcare providers should consider incorporating frailty screening into routine care for older patients with end-stage renal disease and dialysis.

Falls, especially those left unattended, are fatal for the elderly. Several efforts have been made to use the Internet of Things and Machine Learning algorithms to detect falls. All such systems have issues such as (a) sensor placement on the torso and thigh which will be uncomfortable for the elderly. (b) Predictions made on the cloud- the result of the prediction is then sent back to the end device to raise an alert. This is prone to network connectivity and latency issues. We have built an end/device that is wrist-worn and has multiple Inertial Measurement Unit sensors and a heart sensor. We have developed three novel ensemble algorithms (a)Stack(A) (b) Variable weighted Ensemble Voting algorithm-B(VWE(B)), and (c) Variable weighted Ensemble Voting algorithm-C (VWE(C)). Since the ensemble algorithm is run on the end-device built around Qualcomm Snapdragons 820c, we do both feature extraction and selection to reduce data dimensionality. We have used multiple methods such as (a) Identifying features that have maximum impact (b) Principal Component Analysis (PCA) (c) Shapley’s values (d) Cross-Correlation combined with relliefF. We got an accuracy of 97% and specificity of 99%. In this paper, we present the analysis of the system with and without pruning.

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.

Not a lot is known about either death or the dying process. Politicians and many in the medical profession in the UK tend to shy away from interfering with it by not allowing euthanasia as an end of life option for the patient. This is the first paper in a series of two, comparing the situation in human medicine and veterinary medicine, in which euthanasia is well practiced for relieving suffering at the end of an animal’s life. This first part takes the form of a literature review including best practice around end of life care, its deficiencies and the need for assisted dying. Veterinary surgeons are well trained in the ethics of euthanasia and put it to good use in the best interest of their animal patients. In countries which have legalized physician assisted suicide for the terminally ill reporting indicates that it works well, without increases in involuntary euthanasia and most importantly without intimidation of the vulnerable. However, there is still an ever increasing tendency to overuse sedation and opioids at the end of life, which merits further investigation. With advances in medical science able to significantly prolong the dying process, patient autonomy demands a review of the law in the UK.

HD-Zip proteins are unique to plants, and contain a homeodomain closely linked to a leucine zipper motif, which are involved in dimerization and DNA binding. Based on homology in the HD-Zip domain, gene structure and the presence of additional motifs, HD-Zips are divided into four families, HD-Zip I–IV. Phylogenetic and bioinformatics analysis of HD-Zip genes using transcriptomic and genomic datasets from a wide range of plant species indicate that the HD-Zip protein class was already present in green algae. Later, HD-Zips experienced multiple duplication events that promoted neo- and sub-functionalizations. HD-Zip proteins are known to control key developmental and environmental responses, and a growing body of evidence indicates a strict link between members of the HD-Zip II and III families and the auxin machineries. Interactions of HD-Zip proteins with other hormones such as brassinolide and cytokinin have also been described. However, it is striking that among the genes regulated by REV, a HD-Zip III protein playing a key role in apical development, are genes that mediate ABA signaling. Furthermore, HAT1 and HAT3, two HD-Zip II proteins involved in key developmental processes, repress ABA biosynthesis and signaling, indicating an essential role of these factors in adjusting development to changing environment.

The purpose of this study is to investigate the impact of the voltage drop of a three-phase voltage source inverter in driving brushless motors. This study also proposes an enhanced Field Oriented Control scheme that accounts for the inverter voltage drop enabling efficient drive at very low motor-speeds. Experimental results are provided to verify the theoretical study and the proposed control scheme.

Vaccine development against SARS-CoV-2 has been highly successful in slowing down the COVID-19 pandemic. A wide spectrum of approaches including vaccines based on whole viruses, protein subunits and peptides, viral vectors, and nucleic acids have been developed in parallel. For all types of COVID-19 vaccines, good safety and efficacy have been obtained in both preclinical animal studies and in clinical trials in humans. Moreover, emergency use authorization has been granted for all types of COVID-19 vaccines. Although high safety has been demonstrated, rare cases of severe adverse events have been detected after global mass vaccinations. Emerging SARS-CoV-2 variants possessing enhanced infectivity have affected vaccine protection efficacy requiring re-design and re-engineering of novel COVID-19 vaccine candidates. Furthermore, insight into preparedness against emerging SARS-CoV-2 variants and other future viral infections is given.

Abstract: Like other plants, every PV power plant will one day reach the end of its service life. Calculations show that 20,400 tons of PV waste will be generated worldwide by 2030 and 60.2 million tons by 2050, not including the mass of the support structure. Such large amounts of waste pose a potential threat to the environment and people if not properly managed. The paper analysed the options for dealing with PV waste, namely reuse, recycling and landfilling. For recycling as the best option in terms of environmental protection and circular economy, an overview of recycling technologies and the percentage of achievable recycling for the materials contained in each PV system component is given. In addition, the current situation of legislation and recycling of PV modules in Europe was examined with special reference to the Balkan countries. There are a small number of factories for recycling PV modules in Europe, but none in the Balkan countries. The main reason for this is the small amount of PV waste in these countries and consequently the economic unprofitability. For this reason, PV modules (after dismantling the aluminum frame and cables) are mostly disposed of as non-hazardous waste in landfills in these countries. Finally, the main barriers to faster implementation of PV module reuse and recycling are listed, along with guidelines for their removal. The cost of recycling Si modules is about ten times higher than the cost of disposal. To change this ratio in favor of recycling, cheaper recycling methods need to be developed and taxes on landfill disposal need to be increased.

Biotechnological potential of Thermoanaerobacter strain AK15 to produce ethanol and valuable alcohols from carbohydrates and amino acids were evaluated in present study. The strain is highly ethanologenic, producing a maximum of 1.57 mol ethanol per mol of glucose degraded at high liquid-gas phase ratios. The strain degrades most of the sugars tested as well as starch and pretreated hydrolysates of biopolymers (Whatman paper, newspaper, Timothy grass, Rhubarb leaves, and several macroalgae species) to ethanol mainly. The strains degraded serine and threonine when used as a single substrate, producing mainly acetate and ethanol as end products, and the branched-chain amino acids (leucine, isoleucine, valine) when cultivated in the presence of thiosulfate. The main end products from branched-chain amino acids were a mixture of their corresponding branched-chain fatty acids and alcohols. Finally, the strain was also shown to use butyrate as an electron sink during glucose degradation resulting in the reduced product butanol in addition to end products produced from glucose. Thus, strain AK15 is a promising candidate for ethanol and fine chemical production from a range of lignocellulosic and algal biomass.

The recycling of wastes to obtain value-added products is a great challenge in the sustainable economy. In our studies, a mixed precursor containing aluminium scrap from end – of – life vehicles and TiO2 Degussa P25 was used to prepare TiO2 modified Al photocatalyst through solid state reaction. Al scrap and TiO2 Degussa P25 in the ration of n(Ti) / n(Al) = x (x = 0.0 - 2.5%), and acetylacetonate and Tween 80 was mixed under magnetic stirring and sintered using a con-ventional furnance at 550°C. DTA – TG – DTG, X – ray diffraction, Fourier – transform infrared, UV – Vis and photoluminescence spectroscopies were assed to investigate the thermal, structural, optical properties and photocatalytic activity. The effect of aluminium concentration on the characteristics of TiO2 Degussa P25 depending on the above instruments are studied. XRD revealed that the materials have crystal structure of anatase TiO2, rutile TiO2 and aluminium. The opto-electronic properties show that Al addition shifted the absorption spectra toward the visible range. The photocatalytic performance of Al – TiO2 composites was quantified by the degradation of Allura Red solution under a visible condition. The highest photocatalytic activity (79.99%) was achieved for the sample containing 0.5% Al and a higher concentration of Al particles shields the active centres of the semiconductor, thus reducing its photocatalytic activity. Aluminium scrap from end-of-life vehicles can be a source of raw material to be considered in semiconductor production. The spin-trapping technique evidenced that •O2- was the main species generated responsible for the Allura Red degradation.

Traditional end-effector robots for arm rehabilitation are usually attached a­t the hand, primarily focusing on coordinated multi-joint training. Therapy at an individual joint level of the arm for severely impaired stroke survivors is not always possible with existing end-effector robots. The Arm Rehabilitation Robot (AREBO)—an end-effector robot—was designed to provide both single and multi-joint assisted training while retaining the advantages of traditional end-effector robots, such as ease of use and cost-effectiveness (compared to exoskeletons). This work presents the design, optimization, and characterization of AREBO for training single-joint movements of the arm. The AREBO has three actuated and three unactuated degrees of freedom, allowing it to apply forces in any arbitrary direction at its endpoint and self-align to arbitrary orientations within its workspace. The AREBO’s link lengths were optimized to maximize its workspace and manipulability. The AREBO provides single-joint training in both unassisted and adaptive weight support modes using a human arm model to estimate the human arm's kinematics and dynamics without using additional sensors. The characterization of the robot’s controller and the algorithm for estimating the human arm parameters were performed using a two degrees of freedom mechatronic model of the human shoulder joint. The results demonstrate that: (a) the movements of the human arm can be estimated using a model of the human arm and robot’s kinematics, (b) the AREBO has similar transparency to that of existing arm therapy robots in the literature, and (c) the adaptive weight support mode control can adapt to different levels of impairment in the arm. This work demonstrates how an appropriately designed end-effector robot can be used for single-joint training, which can be easily extended to multi-joint training. Future work will focus on the evaluation of the system on patients with any neurological condition requiring arm training.

This note applies the Logistic model approximation to determine the suitable start and end dates for the observed epidemic curves in the total number of cases for different countries. The Logistic model is presented and explicit relations for the beginning and end dates are obtained together with the total epidemic duration. Using data from Brazil, Germany, Italy, and South Korea, the extreme dates are calculated. Since the epidemic onset time is found, a fair comparison of the epidemic curve for these countries is obtained. The result does not depend on the poor statistics available in the early phase of the epidemic when the initial number of infectives is unknown. In fact, the total duration depends only on the characteristic time parameter of the LM model.

One of the uses of Helmholtz resonators is as sound absorbers for room acoustic applications, especially for the low frequency range. Their efficiency is centered around their resonance frequency which is mainly depended on elements of their geometry such as the resonator volume and neck dimensions. Incorporating additional necks on the body of a Helmholtz resonator (depending on whether they are open or closed) has been found to alter the resulted resonance frequency. For this study, tunable Helmholtz resonators to multiple resonance frequencies, are proposed and investigated utilizing additional necks. The resonance frequencies of various multi-neck Helmholtz resonators are first modeled with the use of finite element method (FEM), then calculated with the use of an analytical approach and the results of the two approaches are finally compared. Results of this study show that Helmholtz resonators with multiple resonances at desired frequencies are achievable with the use of additional necks, while FEM and analytical methods can be used for the estimation of the resonance frequencies. Analytical and FEM approach results show a good agreement in cases of small number of additional necks, while the increasing differences in cases of higher neck additions, were attributed to the change in effective length of the necks as demonstrated by FEM. The proposed approach can be useful for tunable sound absorbers for room acoustics applications according to the needs of a space. Also, this approach can be applied in cases of additional tunable air resonances of acoustic instruments (e.g. string instruments).

Multiple Sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves the intricate interplay of different immune cells going awry leading to inflammation, demyelination, and neurodegeneration. Its diagnosis is quite arduous because of the baffling number of symptoms it elicits and the varied clinical manifestation it presents. The simplified criteria (in form of Macdonald’s Criteria) which have got modified several times is now the single most important criteria accepted by neurology bodies for diagnosing MS. Biomarkers from time to time have been explored to simplify the diagnosis and prognosticate MS along with anecessity to monitor treatment outcome. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and rapidly measured, their specificity, safety, and their ability to yield precise results. Biomarkers are classified into various categories including predictive, diagnostic, prognostic, related to disease activity, and monitoring treatment outcome. Each representative of the disease activity category reflects a variety of pathological processes of MS such as neuroaxonal loss, gliosis, demyelination, disability progression, remyelination, etc. This review discusses several promising serum and cerebrospinal fluid biomarkers and imaging biomarkers used in clinical practice. Myelin oligodendrocyte glycoprotein antibody disease which is recently recognized as a definite disease will also be discussed. Furthermore, it sheds light on the criteria and the challenges a biomarker faces to be considered as a standard one.

Adaptation to climate change is being addressed in many domains. This means that there are multiple perspectives on adaptation; often with differing visions resulting in disconnected responses and outcomes. Combining singular perspectives into coherent, combined perspectives that include multiple needs and visions can help to deepen the understanding of various aspects of adaptation and provide more effective responses. Such combinations of perspectives can help to increase the range and variety of adaptation measures available for implementation or avoid maladaptation compared with adaptations derived from a singular perspective. The objective of this paper is to present and demonstrate a framework for structuring the local adaptation responses using the inputs from multiple perspectives. The adaptation response framing has been done by: (i) contextualizing climate change adaptation needs; (ii) analyzing drivers of change; (iii) characterizing measures of adaptation; and (iv) establishing links between the measures with a particular emphasis on taking account of multiple perspectives. This framework was demonstrated with reference to the management of flood risks in a case study Can Tho, Vietnam. The results from the case study show that multiple perspective framing of adaptation responses enhance the understanding of various aspects of adaptation measures, thereby leading to flexible implementation practices.

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.

Multiple sclerosis is a chronic, autoimmune disease that mainly affects the central nervous system, including the brain, spinal cord, and optic nerve. This disease can cause clinical symptoms such as cognitive decline, muscle weakness, spasms, and fatigue in patients, and the onset tends to be younger. Current medication can only prevent or alleviate symptoms, so early diagnosis of this disease can increase patients' chances of treatment. Although the use of nuclear magnetic resonance detection can improve the efficiency of early auxiliary diagnosis, it still requires experienced doctors to spend too much time and energy on comprehensive judgment. To reduce the time cost and improve the efficiency of multiple sclerosis diagnosis, this article proposes a detection and recognition algorithm for multiple sclerosis based on wavelet entropy and self-adaptive particle swarm optimization. Firstly, a triple discrete wavelet transform is performed on the brain image of multiple sclerosis, and then 10 wavelet entropies are extracted from the decomposed wavelet subbands, which can reduce the feature dimensions of the image; Then, the algorithm of self-adaptive particle swarm optimization is used to optimize the feedforward neural network, in order to obtain the optimal connection weights and thresholds during the training process. The result of the model is with an average sensitivity of 92.29±1.89, specificity of 92.54±0.67, precision of 92.48±0.59, accuracy of 92.42±0.88, and F1 score of 84.85±1.74, Matthews correlation coefficient of 92.37±0.96, and Fowlkes223 Mallows Index of 92.38±0.96. The experimental results indicate that this algorithm has a very important data support role in detecting multiple sclerosis.

Multiple Myeloma (MM) is the second most common type of hematological disease and, although it is rare among patients under 40 years of age, its incidence rises in elderly subject. MM manifestations are usually known with the abbreviation CRAB (hyperCalcemia, Renal failure, Anaemia, and lytic Bone lesions). In particular, the extent of the bone disease is negatively related to a decreased patients’ quality of life and, in general, bone disease in MM increases both morbidity and mortality. The detection of lytic bone lesions on imaging, especially CT and MRI, is becoming crucial from the clinical viewpoint to separate asymptomatic from symptomatic MM patients and the detection of focal lytic lesion in these imaging data is becoming relevant even when no clinical symptoms are present. Therefore, radiology is pivotal in the staging and accurate management of patients with MM even in early phases of the disease. In this review we describe the opportunities offered by quantitative imaging and radiomics in multiple myeloma. At present time there is still high variability in the choice between various imaging methods to study MM patients and high variability in image interpretation with suboptimal agreement among readers even in tertiary centres. Therefore, the potential of medical imaging for patients affected by MM is still to be completely unveiled. In the next years, new insights to study MM with medical imaging will derive from artificial intelligence (AI) and radiomics usage in different bone lesions and from the wide implementations of quantitative methods to report CT and MRI. Eventually, medical imaging data can be integrated with the patient's outcomes with the purpose to find radiological biomarkers for predicting the disease prognostic flow and its therapeutic response.

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 &lt; 0.001), with the 3-kerf also reducing crack numbers (p &lt; 0.05) but increasing significantly cracks near the pith (p &lt; 0.01). The 30 mm central hollow significantly reduced central perforation cracking (p &lt; 0.05). Results suggest that a combined treatment approach could help mitigate cracking, enhancing the suitability of wild Mimosa logs for construction use.

Introduction: Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Objectives: To confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and study their correlation with various disease parameters. Methods: Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients’ data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Correlations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. Results: AGEs levels in SLE patients were significantly higher than in HC (p<0.001). We found statistically significant positive correlation with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL6 and oral ulcers. We also found a negative statistically significant correlation with current positivity of anti-nuclear and anti-Ro60 antibodies. Conclusions: AGEs seem to have a role in LES pathophysiology, becoming a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher AGEs levels.

Shaped surfaces are increasingly used in the field of mould making for casting or injection moulding, where future products include shapes with different curvatures. These are surfaces that form convex curves, concave curves, or a combination thereof. Given these machined surfaces, it is important to know the impact of the finishing strategies on these surfaces. This paper deals with the comparison of finishing milling strategies in the production of shaped surfaces and the analysis of different methods for the evaluation of surface topography, surface roughness and the evaluation of deviations. The material used for the experiments was AlCu4Mg aluminium alloy, and Constant Z, Spiral and Spiral circle strategies were chosen for the finishing strategies. The evaluation of surface topography and surface roughness was carried out at three different sample heights with respect to the tool contact with the machined surface. The results showed changes in the toolpaths due to the variation of the effective diameter of the tool cutter to the machined surface as well as the choice of strategy. To produce specimens with corresponding shapes in terms of topography, the Constant Z strategy was the most suitable, in which uniform toolpaths were obtained over the whole height of the sample.

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 edible portion of Cannabis sativa L. are the seeds. The seeds are generally used for the production of hemp oil, appreciated for the high percentage of α-linolenic acid. The waste obtained after seeds oil extraction, reduced in fine powder, is the subject of this study. Since hemp seeds are considered to be a source of many valuable bioactive compounds, the addition of hemp seed flour to durum wheat for making fortified bread could have an effect on the health of consumers. The aim of this study was to use variable percentages of hemp seed flour for the production of bread, and to determine the fortification impact on chemicals, texture, organoleptic characteristics, crumb color, changes in crumb texture, total polyphenols, free radical scavenging activity and amino acids contents. The rheological and chemical qualities of bread samples, obtained by using a durum wheat cultivar Ciclope fortified with defatted hemp seeds flours, were evaluated. The solid residue left after the extraction of the oil from seeds (generally thrown away as waste or added to feed) was shredded and sieved at 0.530 mm (Hemp 1) or 0.236 mm (Hemp 2). Samples of fortified breads were obtained by substitution of variable percentages of durum wheat flour with the two hemp flours (5%, 7.5%, and 10%). Fortified bread’s total phenolic content was in a range of 0.73±0.017 and 1.73±0.029 mg GAE/g and an-ti-radical scavenging activity was included in the range from 1.17±0.099 and 3.18±0.071mmol TEAC/100g, according to the increasing fortification. Comparison between bread made with Ciclope semolina and hemp flour fortified breads, showed a large increase in amino acid content in fortified samples ones. In particular, bread fortified with 10% Hemp 2 flour highlights a greater content of glutamic acid, tyrosine, proline and essential amino acids such as leucine and isoleucine, compared to the other samples with same percentage of substitution. The amount of hemp seed flour influenced the color of the crumb by increasing the yellow index from 18.24 (100% Ciclope) to 21.33 (bread with Hemp 2 flour at 5%).

Tanzania like any other developing countries is depending on uncertain rainfall for their subsistence and commercial agriculture. In this paper the start and end of rains for Mbeya Meteorological Station in Tanzania Mainland was analyzed and critically examined. Data were kindly given by Tanzania Meteorological Agency (TMA) during face to face Statistics in Applied Climatology (fSIAC) workshop which was held at Sokoine University of Agriculture (SUA) the year 2013 prior to online Course on Statistics in Applied climatology (eSIAC). In this study data were analyzed using Instat (for windows version 3.3.7) package developed by the Statistical Services Centre of the University of Reading. The analysis showed that much of rains start early December all the way to May. There is also 50 percent chance of having below and above the mean for both total annual rainfall and number of rains, in other word one in two years the total rains are below means likewise the number of rain days.

This paper provides a data set collected with an underground shaft mobile mapping system equipped with rotated Velodyne VLP-16, Velodyne Ultra Puck VLP-32c, Livox Tele-15, and IMU Xsens MTi-30. The ground truth data was acquired with a geodetic survey including 15 ground control points and 6 Faro Focus 3D Terrestrial Laser Scanner stations of a total 273,784,932 of 3D measurement points. The aim of the paper is to describe the data set of a mining shaft. Obtained mobile mapping data can be the basis for detailed analyzes of the technical condition of the shaft. This data set provides an end-user case study of realistic applications in mobile mapping technology. It provides ground truth data, mobile mapping data and software tools for manipulation and visualization. The project is released and maintained at https://michalpelka.github.io/mine-mapping-dataset/.

This paper presents a novel approach for the recognition of multiple sclerosis (MS) using wavelet entropy and a Particle Swarm Optimization (PSO)-based neural network. MS is a complex neurological disorder with diverse clinical manifestations, often challenging to diagnose accurately. In this study, we leverage wavelet entropy (WE) as a feature extraction method to capture intricate patterns within brain imaging data. These extracted features are then employed to train a neural network model optimized through PSO to enhance classification accuracy. Experimental results on a dataset comprising MS and healthy control subjects demonstrate the effectiveness of our proposed approach, viz., WE-PSONN, which achieves a sensitivity of 91.95±1.15, a specificity of 92.36±0.88, a precision of 92.28±0.88, an accuracy of 92.16±0.90. The combination of advanced signal processing techniques and machine learning optimization holds promise for improving the early diagnosis and management of MS, offering potential benefits to both patients and healthcare providers.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. According to recent studies, cellular senescence caused by telomere shortening may contribute to the development of MS. Aim of the study: to determine the associations of TEP1 rs1760904, rs1713418, TERC rs12696304, rs35073794 gene polymorphisms with the occurrence of MS. Methods: The study included 200 patients with MS and 230 healthy controls. Genotyping of TEP1 rs1760904, rs1713418 and TERC rs12696304, rs35073794 was performed using RT-PCR. Statistical analysis of the obtained data was performed using the program "IBM SPSS Statistics 29.0". Haplotype analysis was performed using the online program "SNPStats". Results: The TERC rs12696304 G allele of this SNP is associated with a 1.4-fold lower odds of developing MS (p=0.035). TERC rs35073794 is associated with an approximately 2.4-fold reduced odds of MS occurrence in the codominant, dominant, overdominant, and additive models (p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). Haplotype analysis shows that the rs1760904-G - rs1713418-A haplotype is statistically significantly associated with a 1.75-fold increased odds of developing MS (p=0.006). The rs12696304-C - rs35073794-A haplotype is statistically significantly associated with a 2-fold decreased odds of developing MS (p=0.008). In addition, the rs12696304-G - rs35073794-A haplotype was found to be statistically significantly associated with a 5.3-fold decreased odds of developing MS (p&lt;0.001). Conclusion: Current evidence may suggest a protective role of TERC SNP in the occurrence of MS, while TEP1 has the opposite effect.

A progressive and chronic neurological condition called MSA (Multiple System Atrophy) is characterized clinically by varying degrees of dysautonomia, cerebellar ataxia, and parkinsonism. The concept of mitochondrial dysregulation in MSA is one perspective in handling this neurodegenerative disease. Damage to functional mitochondria is driven by the presence of ɑ-Synuclein-induced mitochondrial localization. The goal of MSA treatment up until now has been to reduce symptoms. One of the innovations in the treatment of MSA could be the novel idea based on mitochondrial reprogramming pathways. Mitochondrial reprogramming can be done in various ways in which the use of hydrogen, magnesium and low-dose hydrogen peroxide.

Leptospirosis is an important zoonotic disease, causing about 60,000 deaths annually. One of the reasons for the severe course of leptospirosis is a cytokine storm, which develops as a result of an excessive immune response. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis and a bidirectional relationship with many internal organs. A change in the gut microbiota can be caused not only by antibiotics, but also by infectious agents such as the coronavirus or the flu virus. It is known that L. interrogans can change the microbiota of mice. Thus, gut dysbiosis in leptospirosis can affect the clinical course of the disease, through the gut–organ axis. Modulation of intestinal microbiota by probiotics and/or fecal microbiota transplantation in leptospirosis may become an important area of scientific research.

Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.