RESUMEN
The development of microgrid automation depends on information and communication technologies, which are vulnerable to cyber-attacks. Recent advancements in MGs enhance power systems' efficacy and reliability, but cybersecurity remains a significant concern, especially with false data injection attacks (FDIAs) posing serious threats. FDIAs can compromise measurement devices and tamper with State Estimation (SE), risking the seamless operation of MGs. To address this, this paper proposes an efficient Iterative Free Detection of False Data (IFDFD) scheme for detecting FDIAs in microgrid state estimation. The IFDFD scheme uses complex Micro Phasor Measurement Unit (µPMU) measurements and computes nodal power injections to detect FDIAs. Furthermore, the proposed scheme integrates an S-Estimator to eliminate noise errors caused by environmental factors and the component lifespan, making IFDFD robust against sophisticated attackers. The proposed IFDFD scheme has been tested and validated on the modified IEEE 14 bus test system, integrating Distributed Generations (DGs). False data was injected into the measurements to test the scheme's effectiveness. The efficacy of proposed IFDFD scheme has been validated by comparing it to existing method of FDIAs. The obtained result clearly validates the efficacy of the proposed IFDFD scheme.
RESUMEN
Five hundred thirty-seven million people globally suffer from diabetes. Insulin-producing ß cells are reduced in number in most people with diabetes, but most individuals still have some residual ß cells. However, none of the many diabetes drugs in common use increases human ß cell numbers. Recently, small molecules that inhibit dual tyrosine-regulated kinase 1A (DYRK1A) have been shown to induce immunohistochemical markers of human ß cell replication, and this is enhanced by drugs that stimulate the glucagon-like peptide 1 (GLP1) receptor (GLP1R) on ß cells. However, it remains to be demonstrated whether these immunohistochemical findings translate into an actual increase in human ß cell numbers in vivo. It is also unknown whether DYRK1A inhibitors together with GLP1R agonists (GLP1RAs) affect human ß cell survival. Here, using an optimized immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO+) protocol in mouse kidneys bearing human islet grafts, we demonstrate that combination of a DYRK1A inhibitor with exendin-4 increases actual human ß cell mass in vivo by a mean of four- to sevenfold in diabetic and nondiabetic mice over 3 months and reverses diabetes, without alteration in human α cell mass. The augmentation in human ß cell mass occurred through mechanisms that included enhanced human ß cell proliferation, function, and survival. The increase in human ß cell survival was mediated, in part, by the islet prohormone VGF. Together, these findings demonstrate the therapeutic potential and favorable preclinical safety profile of the DYRK1A inhibitor-GLP1RA combination for diabetes treatment.
Asunto(s)
Quinasas DyrK , Exenatida , Harmina , Células Secretoras de Insulina , Péptidos , Proteínas Serina-Treonina Quinasas , Proteínas Tirosina Quinasas , Animales , Humanos , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Exenatida/farmacología , Exenatida/uso terapéutico , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Harmina/farmacología , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Ratones , Péptidos/farmacología , Péptidos/metabolismo , Ponzoñas/farmacología , Ponzoñas/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/agonistas , Quimioterapia Combinada , Proliferación Celular/efectos de los fármacos , XenoinjertosRESUMEN
Glucose monitoring is essential for managing diabetes, and continuous glucose monitoring biosensors can offer real-time monitoring with little invasiveness. However, challenges remain in improving sensor accuracy, selectivity, and overall performance. This article aims to review current trends and recent advancements in glucose-monitoring biosensors while evaluating their benefits and limitations for diabetes monitoring. An analysis of current literature on transdermal glucose sensors was conducted, focusing on detection techniques, novel nanomaterials, and integrated sensor systems. Recent research has led to advancements in electrochemical, optical, electromagnetic, and sonochemical sensors for transdermal glucose detection. The use of novel nanomaterials and integrated sensor designs has improved sensitivity, selectivity, and accuracy. However, issues like calibration requirements, motion artifacts, and skin irritation persist. Transdermal glucose sensors show promise for non-invasive, convenient diabetes monitoring but require further enhancements to address limitations in accuracy, reliability, and biocompatibility. Continued research and innovation focusing on sensor materials, designs, and surface chemistry is needed to optimize biosensor performance and utility. The study offers a comprehensive analysis of the present status of technological advancement and highlights areas that need more research.
RESUMEN
Glutaric Aciduria Type 1 (GA1) is a serious inborn error of metabolism with no pharmacological treatments. A novel strategy to treat this disease is to divert the toxic biochemical intermediates to less toxic or nontoxic metabolites. Here, we report a putative novel target, succinyl-CoA:glutarate-CoA transferase (SUGCT), which we hypothesize suppresses the GA1 metabolic phenotype through decreasing glutaryl-CoA and the derived 3-hydroxyglutaric acid. SUGCT is a type III CoA transferase that uses succinyl-CoA and glutaric acid as substrates. We report the structure of SUGCT, develop enzyme- and cell-based assays, and identify valsartan and losartan carboxylic acid as inhibitors of the enzyme in a high-throughput screen of FDA-approved compounds. The cocrystal structure of SUGCT with losartan carboxylic acid revealed a novel pocket in the active site and further validated the high-throughput screening approach. These results may form the basis for the future development of new pharmacological intervention to treat GA1.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Encefalopatías Metabólicas , Humanos , Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/enzimología , Errores Innatos del Metabolismo de los Aminoácidos/genética , Encefalopatías Metabólicas/tratamiento farmacológico , Encefalopatías Metabólicas/metabolismo , Encefalopatías Metabólicas/enzimología , Glutaratos/metabolismo , Glutaratos/química , Losartán/farmacología , Losartán/química , Coenzima A Transferasas/metabolismo , Coenzima A Transferasas/antagonistas & inhibidores , Coenzima A Transferasas/genética , Coenzima A Transferasas/química , Valsartán , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Cristalografía por Rayos X , Dominio Catalítico , Acilcoenzima A/metabolismo , Acilcoenzima A/química , Modelos Moleculares , Ensayos Analíticos de Alto Rendimiento , Glutaril-CoA Deshidrogenasa/deficienciaRESUMEN
Background: The basic objective of any civilization is to preserve a happy family. The quality of one's sexual encounters is crucial to a happy marriage. Couples' dissatisfaction in this area may be the cause of several social, psychological, and medical issues. The way reality is interpreted, which shapes behaviors and emotions, is established by beliefs. These beliefs, which are among the most frequent causes of male sexual problems, include those relating to high performance, women's sexual enjoyment, and sexual conservatism. Aims: To identify the misconceptions about sexuality among psychiatry patients. Method This cross-sectional study was carried out at the School of Medical Sciences and Research, Sharda University. We enrolled 200 samples and it is assessed through Sexual Beliefs Questionnaire (Male version). Result: Sexual beliefs were assessed in different domains as well as overall sexual belief score was also estimated. The different domains in which the sexual beliefs were scored were sexual conservatism, female sexual power, macho belief, beliefs about women's sexual satisfaction, restrictive attitude toward sex, and sex as an abuse of men's power. Conclusion: The development of both psychiatric and sexological care will benefit from the early identification of the intricate relationships between psychopathology, the adverse effects of antipsychotic medicines, and sexuality. However, longitudinal studies are needed to anticipate the relationship more accurately between sexual dysfunction and sexual beliefs at a larger sample size. Sexual beliefs are significant contributors to sexual dysfunction.
RESUMEN
X-ray Fluorescence Computed Tomography (XFCT) is an emerging non-invasive imaging technique providing high-resolution molecular-level data. However, increased sensitivity with current benchtop X-ray sources comes at the cost of high radiation exposure. Artificial Intelligence (AI), particularly deep learning (DL), has revolutionized medical imaging by delivering high-quality images in the presence of noise. In XFCT, traditional methods rely on complex algorithms for background noise reduction, but AI holds promise in addressing high-dose concerns. We present an optimized Swin-Conv-UNet (SCUNet) model for background noise reduction in X-ray fluorescence (XRF) images at low tracer concentrations. Our method's effectiveness is evaluated against higher-dose images, while various denoising techniques exist for X-ray and computed tomography (CT) techniques, only a few address XFCT. The DL model is trained and assessed using augmented data, focusing on background noise reduction. Image quality is measured using peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM), comparing outcomes with 100% X-ray-dose images. Results demonstrate that the proposed algorithm yields high-quality images from low-dose inputs, with maximum PSNR of 39.05 and SSIM of 0.86. The model outperforms block-matching and 3D filtering (BM3D), block-matching and 4D filtering (BM4D), non-local means (NLM), denoising convolutional neural network (DnCNN), and SCUNet in both visual inspection and quantitative analysis, particularly in high-noise scenarios. This indicates the potential of AI, specifically the SCUNet model, in significantly improving XFCT imaging by mitigating the trade-off between sensitivity and radiation exposure.
RESUMEN
X-ray fluorescence imaging (XFI) can localize diagnostic or theranostic entities utilizing nanoparticle (NP)-based probes at high resolution in vivo, in vitro, and ex vivo. However, small-animal benchtop XFI systems demonstrating high spatial resolution (variable from sub-millimeter to millimeter range) in vivo are still limited to lighter elements (i.e., atomic number Z≤45). This study investigates the feasibility of focusing hard X-rays from solid-target tubes using ellipsoidal lens systems composed of mosaic graphite crystals with the aim of enabling high-resolution in vivo XFI applications with mid-Z (42≤Z≤64) elements. Monte Carlo simulations are performed to characterize the proposed focusing-optics concept and provide quantitative predictions of the XFI sensitivity, in silico tumor-bearing mice models loaded with palladium (Pd) and barium (Ba) NPs. Based on simulation results, the minimum detectable total mass of PdNPs per scan position is expected to be on the order of a few hundred nanograms under in vivo conform conditions. PdNP masses as low as 150 ng to 50 ng could be detectable with a resolution of 600 µm when imaging abdominal tumor lesions across a range of low-dose (0.8 µGy) to high-dose (8 µGy) exposure scenarios. The proposed focusing-optics concept presents a potential step toward realizing XFI with conventional X-ray tubes for high-resolution applications involving interesting NP formulations.
Asunto(s)
Grafito , Grafito/química , Animales , Ratones , Imagen Óptica/métodos , Método de Montecarlo , Nanopartículas/química , Paladio/química , Simulación por Computador , Espectrometría por Rayos X/métodosRESUMEN
The small molecule DYRK1A inhibitor, harmine, induces human beta cell proliferation, expands beta cell mass, enhances expression of beta cell phenotypic genes, and improves human beta cell function i n vitro and in vivo . It is unknown whether the "pro-differentiation effect" is a DYRK1A inhibitor class-wide effect. Here we compare multiple commonly studied DYRK1A inhibitors. Harmine, 2-2c and 5-IT increase expression of PDX1, MAFA, NKX6.1, SLC2A2, PCSK1, MAFB, SIX2, SLC2A2, SLC30A8, ENTPD3 in normal and T2D human islets. Unexpectedly, GNF4877, CC-401, INDY, CC-401 and Leucettine fail to induce expression of these essential beta cell molecules. Remarkably, the pro-differentiation effect is independent of DYRK1A inhibition: although silencing DYRK1A induces human beta cell proliferation, it has no effect on differentiation; conversely, harmine treatment enhances beta cell differentiation in DYRK1A-silenced islets. A careful screen of multiple DYRK1A inhibitor kinase candidate targets was unable to identify pro-differentiation pathways. Overall, harmine, 2-2c and 5-IT are unique among DYRK1A inhibitors in their ability to enhance both beta cell proliferation and differentiation. While beta cell proliferation is mediated by DYRK1A inhibition, the pro-differentiation effects of harmine, 2-2c and 5-IT are distinct, and unexplained in mechanistic terms. These considerations have important implications for DYRK1A inhibitor pharmaceutical development.
RESUMEN
Pathogenic fungi and their spores are ubiquitously present and invade the tissues of higher living plants causing pathogenesis and inevitably death or retarded growth. A group of fungi kills its hosts and consume the dead tissues (necrotrophs), while others feed on living tissue (biotrophs) or combination of two (hemibiotrophs). A number of virulent factors is used by fungal pathogens to inhabit new hosts and cause illness. Fungal pathogens develop specialized structures for complete invasion into plant organs to regulate pathogenic growth. Virulence factors like effectors, mycotoxins, cell wall degrading enzymes and organic acids have varied roles depending on the infection strategy and assist the pathogens to possess control on living tissues of the plants. Infection strategies employed by fungi generally masks the plant defense mechanism, however necrotrophs are best known to harm plant tissues with their poisonous secretion. Interestingly, the effector chemicals released by Biotrophs reduce plant cell growth and regulate plant metabolism in their advantage causing no direct death. All these virulence tools cause huge loss to the agricultural product of pre- harvest crops and post-harvest yields causing low output leading to huge economic losses. This review focusses on comprehensive study of range of virulence factors of the pathogenic fungi responsible for their invasion inside the healthy tissues of plants. The compiled information would influence researchers to design antidote against all virulence factors of fungi relevant to their area of research which could pave way for protection against plant pathogenesis.
Asunto(s)
Productos Agrícolas , Factores de Virulencia , Virulencia , Agricultura , Ciclo CelularRESUMEN
Glutaric Aciduria Type 1 (GA1) is a serious inborn error of metabolism with no pharmacological treatments. A novel strategy to treat this disease is to divert the toxic biochemical intermediates to less toxic or non-toxic metabolites. Here, we report a novel target, SUGCT, which we hypothesize suppresses the GA1 metabolic phenotype through decreasing glutaryl-CoA. We report the structure of SUGCT, the first eukaryotic structure of a type III CoA transferase, develop a high-throughput enzyme assay and a cell-based assay, and identify valsartan and losartan carboxylic acid as inhibitors of the enzyme validating the screening approach. These results may form the basis for future development of new pharmacological intervention to treat GA1.
RESUMEN
Optically active functional noncentrosymmetric architectures might be achieved through the combination of molecules with inscribed optical responses and species of dedicated tectonic character. Herein, we present the new series of noncentrosymmetric cocrystal salt solvates (PPh4)3[M(CN)6](L)n·msolv (M = Cr(III), Fe(III), Co(III); L = polyresorcinol coformers, multiple hydrogen bond donors: 3,3',5,5'-tetrahydroxy-1,19-biphenyl, DiR, n = 2, or 5'-(3,5-dihydroxyphenyl)-3,3â³,5,5â³-tetrahydroxy-1,19:3',1â³-terphenyl, TriRB, n = 1) denoted as MDiR and MTriRB, respectively. The hydrogen-bonded subnetworks {[M(CN)6]3-;Ln}∞ of dmp, neb, or dia topology are formed through structural matching between building blocks within supramolecular cis-bis(chelate)-like {[M(CN)6]3-;(H2L)2(HL)2} or tris(chelate)-like {[M(CN)6]3-;(H2L)3} fragments. The quantum-chemical analysis demonstrates the mixed electrostatic and covalent character of these interactions, with their strength clearly enhanced due to the negative charge of the hydrogen bond acceptor metal complex. The corresponding interaction energy is also dependent on the geometry of the contact and size matching of its components, rotational degree of freedom and extent of the π-electron system of the coformer, and overall fit to the molecular surroundings. Symmetry of the crystal lattices is correlated with the local symmetry of coformers and {complex;(coformer)n} hydrogen-bonded motifs characterized by the absence of the inversion center and mirror plane. All compounds reveal second-harmonic generation activity and photoluminescence diversified by individual UV-vis spectral characteristics of the components, and interesting low-frequency Raman scattering spectra within the subterahertz spectroscopic domain. Vibrational (infrared/Raman), UV-vis electronic absorption (experimental and calculated), and 57Fe Mössbauer spectra together with electrospray ionization mass spectrometry (ESI-MS) data are provided for the complete description of our systems.
RESUMEN
Ascites appear as a clinical manifestation of various disorders, and the presence of raised levels of eosinophils in the peritoneal fluid characterizes eosinophilic ascites, which is an extremely rare disorder. Eosinophilic gastroenteritis is one of the uncommon causes of ascites. If not investigated thoroughly, ascites recurrence in a young female with a history of tuberculosis may be wrongly attributed to tuberculosis recurrence in an endemic country. The etiology of ascites in our case was correctly identified as the subserosal form of eosinophilic ascites. Oral corticosteroids form the mainstay of treatment in such cases. Eosinophilic gastroenteritis is a rare disease, but a thorough workup and a strong clinical suspicion may help in the successful diagnosis and treatment of such cases.
RESUMEN
Background: The fight against tuberculosis in our country has taken a new shape with the inclusion of rapid nucleic acid amplification tests like GeneXpert MTB/RIF assay which rapidly detects Mycobacterium tuberculosis and rifampicin resistance. Rifampicin resistance detected on GeneXpert has been considered as a sine qua non for the presence of isoniazid resistance and hence classified as multidrug-resistant tuberculosis (MDR-TB). However treatment of rifampicin-resistant, isoniazid-monoresistance, and MDR-TB are different. Our study was done with the aim of identification of the prevalence of isoniazid resistance on culture, in cases which had rifampicin resistance on GeneXpert. Methods: Pulmonary samples of patients of presumptive tuberculosis were subjected to GeneXpert testing and liquid MGIT (mycobacterium growth indicator tube) culture. On detection of rifampicin resistance on MTB/RIF assay, the patients were included in our study and cultures were followed-up for sensitivity to isoniazid. A total of 76 patients were included. Results: 76 patients of rifampicin resistance on GeneXpert MTB/RIF assay were followed-up for the sensitivity of isoniazid on culture media. Out of the 76 cases, 62 (81.57%) were found to have isoniazid resistance. Out of the 14 patients, the cultures showed no growth in 6, and in the rest, isoniazid was found to be sensitive. Conclusion: GeneXpert MTB/RIF assay is an excellent modality for the detection of M. tuberculosis and rifampicin resistance. The decision to exclude isoniazid from the treatment regimen in patients with rifampicin resistance should be made only after conducting further molecular/phenotypic tests.
RESUMEN
Neuronal cells made of soma, axon, and dendrites are highly compartmentalized and possess a specialized transport system that can convey long-distance electrical signals for the cross-talk. The transport system is made up of microtubule (MT) polymers and MT-binding proteins. MTs play vital and diverse roles in various cellular processes. Therefore, defects and dysregulation of MTs and their binding proteins lead to many neurological disorders as exemplified by Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and many others. MT-stabilising agents (MSAs) altering the MT-associated protein connections have shown great potential for several neurodegenerative disorders. Peptides are an important class of molecules with high specificity, biocompatibility and are devoid of side effects. In the past, peptides have been explored in various neuronal disorders as therapeutics. Davunetide, a MT-stabilising octapeptide, has entered into phase II clinical trials for schizophrenia. Numerous examples of peptides emerging as MSAs reflect the emergence of a new paradigm for peptides which can be explored further as drug candidates for neuronal disorders. Although small molecule-based MSAs have been reviewed in the past, there is no systematic review in recent years focusing on peptides as MSAs apart from davunetide in 2013. Therefore, a systematic updated review on MT stabilising peptides may shed light on many hidden aspects and enable researchers to develop new therapies for diseases related to the CNS. In this review we have summarised the recent examples of peptides as MSAs.
RESUMEN
The development of nanolayered materials is one of the greatest challenges in nanoscience. Until now, pseudohalogen-bridged nanosheets using the mechanical exfoliation method have not been reported. A state-of-the-art material, {[FeII(3-acetylpyridine)2][HgII(µ-SCN)4]}n (1), has been developed to achieve the goal. The compound forms a two-dimensional (2D) coordination polymer with weak out-of-plane van der Waals interactions and has an intrinsic tendency to form shear planes perpendicular to the crystallographic c-direction. These structural features predispose 1 to mechanical exfoliation realized by employing the "Scotch-tape method". As a result, nanosheets were fabricated and characterized by digital optical microscopy, scanning electron microscopy, and atomic force microscopy. The nanosheets were found to have a minimum thickness of â¼15 nm and a lateral size of several micrometers. As the first example of thiocyanato-bridged coordination nanosheets, these materials extend the scope of 2D materials and potentially pave the way toward developing nanolayered materials.
RESUMEN
Increased innovation on finding new ways to generate energy from different sources to meet the growing demand of consumers has led to various challenges in controlling the power network when it faces different disruptions. To address these challenges, a new approach has been proposed in this research paper, which combines a controller with a soft computing technique called Particle Swarm Optimization (PSO). The study considers a power system with four units, where three different energy sources are utilized and distributed across two areas. Each area has two power sources, with one area having a combination of thermal and gas power plants, and the other area consisting of a nuclear power plant and a gas power plant. Transmitting power from the nuclear power plant is particularly complex due to its high sensitivity to disturbances. Therefore, an intelligent and efficient controller is needed to ensure robust control in this type of power network that includes nuclear power. The paper also conducts a thorough analysis of the harmful emissions associated with electricity generation from the different power plants considered. The goal is to reduce the carbon footprint associated with power generation. The proposed work and analysis in the paper are implemented using the MATLAB/SIMULINK environment.
RESUMEN
Research on isomers is highly desirable due to their prospective role in better understanding of physicochemical properties of similar systems and further development of multifunctional molecular materials. Iron(II) and tetra(thiocyanato)mercury(II) ions self-assembled in the presence of 2-acetylpyridine (2-acpy) excess to form two {[Fe(2-acpy)][Hg(µ-SCN)4]}n isomers: two-dimensional (2D) centrosymmetric layers with folded ring structural motifs (1) and three-dimensional (3D) chiral networks with right- or left-handed {···Fe-NCS-Hg-SCN···}∞ helixes (2). New methods of designing and synthesizing functional thiocyanate-bridged materials have been proposed. In addition, the similarity between 1 and 2 allowed for the description of subtle changes in IR and UV-visible spectra. Moreover, 2 shows spontaneous resolution, and it crystallizes in the noncentrosymmetric space group P21, leading to the occurrence of nonlinear optical activity in circular dichroism studies and second harmonic generation (SHG). At room temperature, the SH susceptibility for powder sample 2 reached 6.0 × 10-11 esu. Ab initio calculations indicated the electric polarization vector and the crystallographic twofold screw axis pass through the aromatic ring. Magnetic studies for 1 and 2 revealed high-spin iron(II) with zero-field splitting at low temperatures. Analysis of magnetic data gave |D| = 37.45 cm-1, |E/D| = 5.59 cm-1, and ⟨g⟩ = 2.15 for 1, |D| = 36.78 cm-1, |E/D| = 4.92 cm-1, and ⟨g⟩ = 2.18 for 2, and information about the orientation of magnetic anisotropy vectors for both compounds.
RESUMEN
Self-assembly FeII complexes of phenazine (Phen), quinoxaline (Qxn), and 4,4'-trimethylenedipyridine (Tmp) with tetrahedral building blocks of [HgII (XCN)4 ]2- (X=S or Se) formed six new high-dimensional frameworks with the general formula of [Fe(L)m ][Hg(XCN)4 ]â solvents (L=Phen, m/X=2/S, 1; L=Qxn, m/X=2/S, 2; L=Qxn, m/X=1/S, 3; L=Qxn, m/X=1/Se, 3-Se; L=Tmp, m/X=1/S, 4; and L=Tmp, m/X=1/Se, 4-Se). 1, 3, and 3-Se show an intense sub-terahertz (sub-THz) absorbance of around 0.60â THz due to vibrations of the solvent molecules coordinated to the FeII ions and crystallization organic molecules. In addition, crystals of 1, 4, and 4-Se display low-frequency Raman scattering with exceptionally low values of 0.44, 0.51, and 0.53â THz, respectively. These results indicate that heavy metal FeII -HgII systems are promising platforms to construct sub-THz absorbers.