Background: Lipid-lowering is an important intervention to reduce cardiovascular morbidity and mortality after ST-Elevation myocardial infarction. This study aimed to assess the proportion of such patients achieving guideline-directed therapeutic low-density lipoprotein cholesterol targets while on lower-range high-intensity statin treatment.
Methods: This is a cross-sectional study conducted in Shahid Gangalal National Heart Centre, a tertiary cardiac center in Kathmandu, Nepal, from November 2021 to July 2022 among admitted acute ST-Elevation myocardial infarction patients who were prescribed a lower range of high-intensity statin therapy, Atorvastatin 40mg and Rosuvastatin 20 mg.
Shadow Shield Whole Body Counter (SSWBC) is used to estimate internal dose of radiation workers due to the intake of fission and activation products. The SSWBC geometry was numerically modelled in FLUKA code. The computational model was validated by comparing the experimental and simulated counting efficiencies (CEs), also known as response, using Bhabha Atomic Research Centre (BARC) reference BOttle Mannequin Absorption (BOMAB) phantom.
View Article and Find Full Text PDFAn automated standing type Quick Scan Whole Body Monitor (QS-WBM) has been developed for the measurement of internal radioactive contamination due to high energy photon (HEP) emitters (E >200 keV). Individuals are monitored while standing on a platform inside QS-WBM at specified reference position. Instances may occur where individuals deviate from their monitoring position, potentially leading to errors in the measurement of the body content.
View Article and Find Full Text PDFQuantitative experiments are essential for investigating, uncovering, and confirming our understanding of complex systems, necessitating the use of effective and robust experimental designs. Despite generally outperforming other approaches, the broader adoption of model-based design of experiments (MBDoE) has been hindered by oversimplified assumptions and computational overhead. To address this, we present PARameter SEnsitivity Clustering (PARSEC), an MBDoE framework that identifies informative measurable combinations through parameter sensitivity (PS) clustering.
View Article and Find Full Text PDFHypothesis: Harnessing electrical energy from salinity gradients, particularly for powering micro and nanoscale devices, has become a focal point of recent research attention, due to its renewable and biocompatible nature. Much of the reported research in that direction revolves around optimizing the membrane architecture and the charge distribution to maximize the induced electric potential, with no particular emphasis on the fluid rheology. However, many of the modern miniature systems, typically the bio-inspired ones, concern fluids with complex rheological characteristics, where the results for Newtonian solvents may not trivially apply.
View Article and Find Full Text PDFDengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system.
View Article and Find Full Text PDFCurr Opin Pharmacol
December 2024
Cyclins along with their catalytic units, Cyclin-dependent kinases (CDKs) regulate the cell cycle transition and transcription; and are essentially known as 'master regulators' in modulating DNA damage response (DDR) and replication stress. In addition to influencing DNA repair and damage signaling, CDKs also play a pivotal role in cell division fidelity and the maintenance of genomic integrity after DNA damage. In this review, we focus on the intricate ways by which specific CDKs mainly CDK7, CDK9, and CDK12/13, regulate the cell cycle progression and transcription and how their modulation can lead to lethal effects on the integrity of the genome.
View Article and Find Full Text PDFDengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system.
View Article and Find Full Text PDFIn a solid, the electronic subsystem can exhibit incipient order with lower point group symmetry than the crystal lattice. Ultrafast external fields that couple exclusively to electronic order parameters have rarely been investigated, however, despite their potential importance in inducing exotic effects. Here we show that when inversion symmetry is broken by the antiferromagnetic order in CrO, transmitting a linearly polarized light pulse through the crystal gives rise to an in-plane rotational symmetry-breaking (from C to C) via optical rectification.
View Article and Find Full Text PDFTranscription and splicing of pre-messenger RNA are closely coordinated, but how this functional coupling is disrupted in human diseases remains unexplored. Using isogenic cell lines, patient samples, and a mutant mouse model, we investigated how cancer-associated mutations in SF3B1 alter transcription. We found that these mutations reduce the elongation rate of RNA polymerase II (RNAPII) along gene bodies and its density at promoters.
View Article and Find Full Text PDFEvol Med Public Health
December 2023
Age-specific dose coefficients are required to assess internal exposure to the general public. This study utilizes reference age-specific biokinetic models of iodine to estimate the total number of nuclear disintegrations ã(,τ) occurring in source regions () during the commitment time (τ). Age-specific S values are estimated for 35 target regions due toI present in 22using data from 10 paediatric reference computational phantoms (representing five ages for both sexes) published recently by the International Commission of Radiation Protection (ICRP).
View Article and Find Full Text PDFA novel three-dimensional (3D) cyclophane molecule was synthesized and fully characterized. Cyclophane , which can form a N heterocyclic carbene, was tested for conversion of certain epoxides (-) [scheme 2] to cyclic carbonates in the presence of CO. Propylene oxide () was found to have more reactivity with cyclophane compared to the other epoxides.
View Article and Find Full Text PDFPlasma membrane-induced protein folding and conformational transitions play a central role in cellular homeostasis. Several transmembrane proteins are folded in the complex lipid milieu to acquire a specific structure and function. Bacterial pore forming toxins (PFTs) are proteins expressed by a large class of pathogenic bacteria that exploit the plasma membrane environment to efficiently undergo secondary structure changes, oligomerize, and form transmembrane pores.
View Article and Find Full Text PDFWe report an electrode-embedded on-chip platform technology for the precise determination of ultra-short (of the order of a few nanoseconds) relaxation times of dilute polymer solutions, by deploying time-alternating electrical voltages. Our methodology delves into the sensitive dependence of the contact line dynamics of a droplet of the polymer solution atop a hydrophobic interface in response to the actuation voltage, resulting in a non-trivial interplay between the time-evolving electrical, capillary, and viscous forces. This culminates into a time-decaying dynamic response that mimics the features of a damped oscillator having its 'stiffness' mapped with the polymeric content of the droplet.
View Article and Find Full Text PDFUpon intense femtosecond photoexcitation, a many-body system can undergo a phase transition through a nonequilibrium route, but understanding these pathways remains an outstanding challenge. Here, we use time-resolved second harmonic generation to investigate a photoinduced phase transition in Ca_{3}Ru_{2}O_{7} and show that mesoscale inhomogeneity profoundly influences the transition dynamics. We observe a marked slowing down of the characteristic time τ that quantifies the transition between two structures.
View Article and Find Full Text PDFMore than a hundred thousand dengue cases are diagnosed in India annually, and about half of the country's population carries dengue virus-specific antibodies. Dengue propagates and adapts to the selection pressures imposed by a multitude of factors that can lead to the emergence of new variants. Yet, there has been no systematic analysis of the evolution of the dengue virus in the country.
View Article and Find Full Text PDFIntroduction: VPS45 belongs to the Sec1/Munc18 family of proteins, which interact with and regulate Qa-SNARE function during membrane fusion. We have shown previously that VPS45 interacts with the SYP61/SYP41/VTI12 SNARE complex, which locates on the -Golgi network (TGN). It is required for SYP41 stability, and it functions in cargo trafficking to the vacuole and in cell expansion.
View Article and Find Full Text PDFUnlabelled: Transcription and splicing of pre-messenger RNA are closely coordinated, but how this functional coupling is disrupted in human disease remains unexplored. Here, we investigated the impact of non-synonymous mutations in SF3B1 and U2AF1, two commonly mutated splicing factors in cancer, on transcription. We find that the mutations impair RNA Polymerase II (RNAPII) transcription elongation along gene bodies leading to transcription-replication conflicts, replication stress and altered chromatin organization.
View Article and Find Full Text PDFThe black nectar produced by Melianthus flowers is thought to serve as a visual attractant to bird pollinators, but the chemical identity and synthesis of the black pigment are unknown. A combination of analytical biochemistry, transcriptomics, proteomics, and enzyme assays was used to identify the pigment that gives Melianthus nectar its black color and how it is synthesized. Visual modeling of pollinators was also used to infer a potential function of the black coloration.
View Article and Find Full Text PDFArtificial membrane systems can serve as models to investigate molecular mechanisms of different cellular processes, including transport, pore formation, and viral fusion. However, the current, such as SUVs, GUVs, and the supported lipid bilayers suffer from issues, namely high curvature, heterogeneity, and surface artefacts, respectively. Freestanding membranes provide a facile solution to these issues, but current systems developed by various groups use silicon or aluminum oxide wafers for fabrication that involves access to a dedicated nanolithography facility and high cost while conferring poor membrane stability.
View Article and Find Full Text PDFSeveral bacterial infections are mediated by pore-forming toxins (PFTs), a subclass of proteins that oligomerize on mammalian cell membranes forming lytic nanopores. Cytolysin A (ClyA), an α-PFT, undergoes a dramatic conformational change restructuring its two membrane-binding motifs (the β-tongue and the N-terminus helix), during pore formation. A complete molecular picture for this key transition and the driving force behind the secondary structure change upon membrane binding remain elusive.
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