The Rise of RNA-Based Therapeutics: Recent Advances and Therapeutic Potential

In recent years, RNA-based therapeutics have emerged as a groundbreaking field, offering innovative approaches for drug development and therapeutic interventions. This review article presents a comprehensive exploration of the advancements in RNA-based therapeutics, focusing on key modalities such as RNA interference (RNAi), antisense oligonucleotides (ASOs), messenger RNA (mRNA) vaccines, and other emerging RNA-based therapies. The introduction provides an insightful overview of the potential of RNA as a therapeutic target, highlighting its unique mechanisms of action and its transformative role in precision medicine. Subsequently, the review delves into the intricacies of RNAi, explaining the function of small interfering RNAs (siRNAs) and microRNAs (miRNAs) in selectively silencing disease-associated genes, thereby opening new avenues for therapeutic interventions. Antisense oligonucleotides (ASOs) are discussed in detail, elucidating how they target mRNA for degradation or modulation of splicing, offering promising solutions for treating genetic disorders, neurodegenerative diseases, and viral infections. Additionally, the groundbreaking success of mRNA vaccines is explored, with an emphasis on their role in combatting infectious diseases like COVID-19 and their potential application in cancer immunotherapy and other therapeutic areas. Addressing the critical issue of delivery challenges in RNA-based therapeutics, the review presents various strategies to enhance stability, cellular uptake, and minimize immunogenicity, thereby improving the effectiveness of these therapies in reaching their intended targets. Clinical successes and challenges of RNA-based therapeutics are critically evaluated, providing insights into ongoing clinical trials and approved therapies. Success stories underscore the transformative potential of RNA-based treatments, while safety concerns are addressed, paving the way for safer and more efficient therapeutic applications. The review concludes by exploring future prospects and innovations in the field, highlighting novel delivery strategies, advancements in RNA editing technologies, and the promise of combination therapies to augment therapeutic outcomes. Regulatory considerations and commercialization challenges are also discussed, offering an understanding of the regulatory landscape for RNA-based therapeutics and the potential for market growth. In conclusion, this review article serves as an informative resource for researchers, clinicians, and pharmaceutical professionals, shedding light on the rapid progress in RNA-based therapeutics and their potential to revolutionize disease treatment. By integrating knowledge from diverse sources, this review contributes to advancing the field and underscores the exciting possibilities of RNA-based interventions in improving patient outcomes and addressing unmet medical needs

Noise analysis of the Indian Pulsar Timing Array data release I

The Indian Pulsar Timing Array (InPTA) collaboration has recently made its first official data release (DR1) for a sample of 14 pulsars using 3.5 years of uGMRT observations. We present the results of single-pulsar noise analysis for each of these 14 pulsars using the InPTA DR1. For this purpose, we consider white noise, achromatic red noise, dispersion measure (DM) variations, and scattering variations in our analysis. We apply Bayesian model selection to obtain the preferred noise models among these for each pulsar. For PSR J1600$-$3053, we find no evidence of DM and scattering variations, while for PSR J1909$-$3744, we find no significant scattering variations. Properties vary dramatically among pulsars. For example, we find a strong chromatic noise with chromatic index $\sim$ 2.9 for PSR J1939+2134, indicating the possibility of a scattering index that doesn't agree with that expected for a Kolmogorov scattering medium consistent with similar results for millisecond pulsars in past studies. Despite the relatively short time baseline, the noise models broadly agree with the other PTAs and provide, at the same time, well-constrained DM and scattering variations.Comment: Accepted for publication in PRD, 30 pages, 17 figures, 4 table

Multi-band Extension of the Wideband Timing Technique

The wideband timing technique enables the high-precision simultaneous estimation of Times of Arrival (ToAs) and Dispersion Measures (DMs) while effectively modeling frequency-dependent profile evolution. We present two novel independent methods that extend the standard wideband technique to handle simultaneous multi-band pulsar data incorporating profile evolution over a larger frequency span to estimate DMs and ToAs with enhanced precision. We implement the wideband likelihood using the libstempo python interface to perform wideband timing in the tempo2 framework. We present the application of these techniques to the dataset of fourteen millisecond pulsars observed simultaneously in Band 3 (300 - 500 MHz) and Band 5 (1260 - 1460 MHz) of the upgraded Giant Metrewave Radio Telescope (uGMRT) as a part of the Indian Pulsar Timing Array (InPTA) campaign. We achieve increased ToA and DM precision and sub-microsecond root mean square post-fit timing residuals by combining simultaneous multi-band pulsar observations done in non-contiguous bands for the first time using our novel techniques.Comment: Submitted to MNRA

Assessing Trustworthy AI in times of COVID-19. Deep Learning for predicting a multi-regional score conveying the degree of lung compromise in COVID-19 patients

Abstract—The paper's main contributions are twofold: to demonstrate how to apply the general European Union’s High-Level Expert Group’s (EU HLEG) guidelines for trustworthy AI in practice for the domain of healthcare; and to investigate the research question of what does “trustworthy AI” mean at the time of the COVID-19 pandemic. To this end, we present the results of a post-hoc self-assessment to evaluate the trustworthiness of an AI system for predicting a multi-regional score conveying the degree of lung compromise in COVID-19 patients, developed and verified by an interdisciplinary team with members from academia, public hospitals, and industry in time of pandemic. The AI system aims to help radiologists to estimate and communicate the severity of damage in a patient’s lung from Chest X-rays. It has been experimentally deployed in the radiology department of the ASST Spedali Civili clinic in Brescia (Italy) since December 2020 during pandemic time. The methodology we have applied for our post-hoc assessment, called Z-Inspection®, uses socio-technical scenarios to identify ethical, technical and domain-specific issues in the use of the AI system in the context of the pandemic.</p

A Kinetic Study of Peroxydisulphate Oxidation of Sulphadrugs - Oxidation of Sulphanilamide

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450 mm Silicon Wafer: Economical and Technical Challenges 1

Following Moore’s law semiconductor industry had acquired unprecedented growth by providing more capability at equal or low cost. Semiconductor industry increased the wafer size with new fab architecture at every ten years while technological and device advancements like miniaturization, new materials, silicon waste reduction, design and manufacturing process improvements at every two years which has reduced the cost per function. The capital investments require in overall factory integration has increased. This paper discusses the economical and technical issues regarding the transition to 450 mm. Technical challenges can be handled by making contemporary changes across semiconductor industry. Keywords- 450 mm Wafer Diameter, fab economis, manufacturing process, wafer thickness. I

Pharmacognostical and phytochemical evaluation of Lycopodium clavatum stem

228-232Paper presents pharmacognostical and phytochemical study of L. clavatum. Ferulic acid, a potential antioxidant present in this species, has been studied through HPTLC and may be utilized by industries for quality evaluation, ensuring successful commercial exploitation of this drug

Minimalistic Cationic Scaffolds Exhibiting Excited State Intramolecular Proton Transfer (ESIPT), White Light Emission and Photo-click reactions

The excited state intramolecular proton transfer (ESIPT) process significantly influences the photophysics of (bio)molecules. ESIPT is facilitated by the spatial proximity of the proton donating and accepting residues as well as by the acidity of the proton being transferred. While neutral and zwitterionic molecules undergoing ESIPT are well reported in the literature, cationic scaffolds capable of ESIPT are conspicuously absent. Here, we present two cationic organic scaffolds viz. DADAB.TFA and DATzTz.TFA that exhibit rapid Anilinium-to-Azonium (Ano-Azo) ESIPT resulting in unique photophysical and photochemical outcomes. Strong 5-membered and 6-membered intramolecular hydrogen bonding (IHB) in DADAB.TFA and DATzTz.TFA, respectively, ensured the structural rigidity and planarity necessary for ESIPT. It also rendered DADAB.TFA emissive, with a moderate Stokes shift of 6597 cm-1 in H2O along with Anti-Kasha behaviour of excitation-dependent (Ex-De) emission. On the other hand, the DATzTz.TFA showed a large Stokes shift of 10209 cm-1 (in acetone). The emission of DADABH2+2 from its tautomeric azonium state gained prominence with the acidity of the protonating species. This was employed to achieve single-component white light emission (WLE) using DATzTz.TFA. Transient absorption spectroscopy (TAS) provided the lifetime of excited state absorption (ESA) as 0.85 ps for DADAB.TFA, whereas the lifetime of 1.2 ps was observed for stimulated emission (SE). Upon photoexcitation, DADAB.TFA also underwent photo-click reaction with aldehydes to yield more emissive benzimidazole frameworks. This work presents the design of new minimalistic cationic scaffolds undergoing ESIPT and expands the repertoire of photophysically-active and photochemically-reactive charged organic scaffolds