Advances in Methods for tRNA Sequencing and Quantification

In the past decade tRNA sequencing (tRNA-seq) has attracted considerable attention as an important tool for the development of novel approaches to quantify highly modified tRNA species and to propel tRNA research aimed at understanding the cellular physiology and disease and development of tRNA-based therapeutics. Many methods are available to quantify tRNA abundance while accounting for modifications and tRNA charging/acylation. Advances in both library preparation methods and bioinformatic workflows have enabled developments in next-generation sequencing (NGS) workflows. Other approaches forgo NGS applications in favor of hybridization-based approaches. In this review we provide a brief comparative overview of various tRNA quantification approaches, focusing on the advantages and disadvantages of these methods, which together facilitate reliable tRNA quantification

Quantum master equation for electron transport through quantum dots and single molecules

A quantum master equation (QME) is derived for the many-body density matrix of an open current-carrying system weakly coupled to two metal leads. The dynamics and the steady-state properties of the system for arbitrary bias are studied using projection operator techniques, which keep track of number of electrons in the system. We show that coherences between system states with different number of electrons, n, (Fock space coherences) do not contribute to the transport to second order in system-lead coupling. However, coherences between states with the same n may effect transport properties when the damping rate is of the order or faster then the system Bohr frequencies. For large bias, when all the system many-body states lie between the chemical potentials of the two leads, we recover previous results. In the rotating wave approximation (when the damping is slow compared to the Bohr frequencies of the system), the dynamics of populations and the coherences in the system eigenbasis are decoupled. The QME then reduces to a birth and death master equation for populations.Comment: 22 pages, 8 figures, paper accepted in Phys. Rev.

Nonlinear optical spectroscopy of single, few, and many molecules; nonequilibrium Green's function QED approach

Nonlinear optical signals from an assembly of N noninteracting particles consist of an incoherent and a coherent component, whose magnitudes scale \sim N and \sim N(N-1), respectively. A unified microscopic description of both types of signals is developed using a quantum electrodynamical (QED) treatment of the optical fields. Closed nonequilibrium Green's function expressions are derived that incorporate both stimulated and spontaneous processes. General (n+1)-wave mixing experiments are discussed as an example of spontaneously generated signals. When performed on a single particle, such signals cannot be expressed in terms of the nth order polarization, as predicted by the semiclassical theory. Stimulated processes are shown to be purely incoherent in nature. Within the QED framework, heterodyne-detected wave mixing signals are simply viewed as incoherent stimulated emission, whereas homodyne signals are generated by coherent spontaneous emission.Comment: article: 33 pages (preprint format!) ''paper.tex'' figures: 17 figures (.eps) in folder ``figures'

Analysis of 3.5 Million SARS-CoV-2 Sequences Reveals Unique Mutational Trends with Consistent Nucleotide and Codon Frequencies

Background: Since the onset of the SARS-CoV-2 pandemic, bioinformatic analyses have been performed to understand the nucleotide and synonymous codon usage features and mutational patterns of the virus. However, comparatively few have attempted to perform such analyses on a considerably large cohort of viral genomes while organizing the plethora of available sequence data for a month-by-month analysis to observe changes over time. Here, we aimed to perform sequence composition and mutation analysis of SARS-CoV-2, separating sequences by gene, clade, and timepoints, and contrast the mutational profile of SARS-CoV-2 to other comparable RNA viruses.Methods: Using a cleaned, filtered, and pre-aligned dataset of over 3.5 million sequences downloaded from the GISAID database, we computed nucleotide and codon usage statistics, including calculation of relative synonymous codon usage values. We then calculated codon adaptation index (CAI) changes and a nonsynonymous/synonymous mutation ratio (dN/dS) over time for our dataset. Finally, we compiled information on the types of mutations occurring for SARS-CoV-2 and other comparable RNA viruses, and generated heatmaps showing codon and nucleotide composition at high entropy positions along the Spike sequence.Results: We show that nucleotide and codon usage metrics remain relatively consistent over the 32-month span, though there are significant differences between clades within each gene at various timepoints. CAI and dN/dS values vary substantially between different timepoints and different genes, with Spike gene on average showing both the highest CAI and dN/dS values. Mutational analysis showed that SARS-CoV-2 Spike has a higher proportion of nonsynonymous mutations than analogous genes in other RNA viruses, with nonsynonymous mutations outnumbering synonymous ones by up to 20:1. However, at several specific positions, synonymous mutations were overwhelmingly predominant.Conclusions: Our multifaceted analysis covering both the composition and mutation signature of SARS-CoV-2 gives valuable insight into the nucleotide frequency and codon usage heterogeneity of SARS-CoV-2 over time, and its unique mutational profile compared to other RNA viruses

Microwave synthesis of single-crystalline perovskite BiFeO3 nanocubes for photoelectrode and photocatalytic applications

A simple microwave synthesis procedure has been developed for the single-crystalline perovskite nanocubes composed of bismuth ferrite (BiFeO(3)). Typical nanocubes had sizes ranging from 50 to 200 nm. The single-crystalline nature of nanocubes was confirmed by high resolution transmission electron microscopy and selected area electron diffraction pattern. X-ray diffraction pattern showed the rhombohedral phase with R3c space group. The material showed photoinduced water oxidation activity in both photoelectrochemical and photocatalytic modes. It could become a useful material for photoelectrode and photocatalytic applications. (C) 2008 American Institute of Physicsclose878

Splicing Dysregulation Contributes to the Pathogenicity of Several F9 Exonic Point Variants

Background: Pre‐mRNA splicing is a complex process requiring the identification of donor site, acceptor site, and branch point site with an adjacent polypyrimidine tract sequence. Splicing is regulated by splicing regulatory elements (SREs) with both enhancer and suppressor functions. Variants located in exonic regions can impact splicing through dysregulation of native splice sites, SREs, and cryptic splice site activation. While splicing dysregulation is considered primary disease‐inducing mechanism of synonymous variants, its contribution toward disease phenotype of non‐synonymous variants is underappreciated. Methods: In this study, we analyzed 415 disease‐causing and 120 neutral F9 exonic point variants including both synonymous and non‐synonymous for their effect on splicing using a series of in silico splice site prediction tools, SRE prediction tools, and in vitro minigene assays. Results: The use of splice site and SRE prediction tools in tandem provided better prediction but were not always in agreement with the minigene assays. The net effect of splicing dysregulation caused by variants was context dependent. Minigene assays revealed that perturbed splicing can be found. Conclusion: Synonymous variants primarily cause disease phenotype via splicing dysregulation while additional mechanisms such as translation rate also play an important role. Splicing dysregulation is likely to contribute to the disease phenotype of several non‐synonymous variants

PTCOG Head and Neck Subcommittee Consensus Guidelines on Particle Therapy for the Management of Head and Neck Tumors

Purpose: Radiation therapy is a standard modality in the treatment for cancers of the head and neck, but is associated with significant short- and long-term side effects. Proton therapy, with its unique physical characteristics, can deliver less dose to normal tissues, resulting in fewer side effects. Proton therapy is currently being used for the treatment of head and neck cancer, with increasing clinical evidence supporting its use. However, barriers to wider adoption include access, cost, and the need for higher-level evidence.Methods: The clinical evidence for the use of proton therapy in the treatment of head and neck cancer are reviewed here, including indications, advantages, and challenges.Results: The Particle Therapy Cooperative Group Head and Neck Subcommittee task group provides consensus guidelines for the use of proton therapy for head and neck cancer.Conclusion: This report can be used as a guide for clinical use, to understand clinical trials, and to inform future research efforts.</p

CLINICAL FEATURES AND PATTERN OF PRESENTATION OF BREAST DISEASES IN SURGICAL OUTPATIENT CLINIC OF A TERTIARY HOSPITAL

Objective: The objective of thedu was to characterize the clinical features and pattern of presentation of breast diseases as observed in our practice. Materials and Methods: A prospective study of 121 consecutive patients with breast complaints presenting in our Surgical Outpatient Clinics. The relevant data were collected using the prescribed forms and was analyzed using Epi Info 2003, Mann–Whitney (test of two groups) Chi-squared and Fishers exact test was used to compare parameters of benign and malignant groups. P value <0.05 was considered as significant. Results: One hundred and nineteen patients were females, two were males. The age range was 14–70 years. Forty two (34.7%) patients were in the 21–30 year age group. The commonest symptoms were breast lump in 111 (91.7%) patients, and breast pain in 28 (23.1%) patients. Breast pain was a significant presenting complaint in patients with breast malignancy (P=0.026). On clinical examination 103 (85.1%) patients had palpable lumps, and seven patients were normal. Forty four patients (36.3%) had malignant disease, seventy patients (57.8%) had benign breast diseases and seven were normal. Fifty nine of the 70 benign diseases were fibroadenoma. One hundred and three patients (85%) had appropriate therapy, while 18 patients (14.8%), including eight with malignant disease absconded. Conclusion: In the study, a breast lump was the commonest clinical feature of breast disease. Over 60% of these were benign. Breast pain was a statistically significant presentation in patients with malignant breast disease. One in seven of the patients absconded

Band gap tuning of lead-substituted BaSnO3 for visible light photocatalysis

The Pb substitution effect was investigated experimentally and theoretically on the crystal structure of BaSnO3 and on the photo-oxidation activity of H2O. The chemically doped Pb in BaSnO3 induced a concentration-dependent redshift of the experimental band gap (BG). The BaPb0.8Sn0.2O3 system produced 32 mu mol/h of O-2 under lambda >= 420 nm photons, but no O-2 for BaSnO3. The DFT calculations of BaPbxSn1-xO3 (x=0,0.5,1) by using generalized approximation, implying the BG alteration and the photocatalytic activity of BaPbxSn1-xO3, are due to the induced Pb 6s orbital in the BG of BaSnO3. Thus Pb modified the insulating nature of BaSnO3 to semiconducting and semimetallic. (c) 2007 American Institute of Physicsclose343