55 research outputs found
Visualizing Relationships between Related Variables: Improving Physics Education through D3.js Network Visualizations
phiMap is a web application started by Cal Poly professors and students to aid professors in teaching physics. I developed Javascript visualizations for phiMap that serve to simplify the processes of both teaching and learning physics. These visualizations aim to present relationships between physics variables in an easy to understand manner, and they could eventually have a huge impact on physics education
M. tuberculosis Transcription Machinery: A Review on the Mycobacterial RNA Polymerase and Drug Discovery Efforts
Mycobacterium tuberculosis (MTB) is the main source of tuberculosis (TB), one of the oldest known diseases in the human population. Despite the drug discovery efforts of past decades, TB is still one of the leading causes of mortality and claimed more than 1.5 million lives worldwide in 2020. Due to the emergence of drug-resistant strains and patient non-compliance during treatments, there is a pressing need to find alternative therapeutic agents for TB. One of the important areas for developing new treatments is in the inhibition of the transcription step of gene expression; it is the first step to synthesize a copy of the genetic material in the form of mRNA. This further translates to functional protein synthesis, which is crucial for the bacteria living processes. MTB contains a bacterial DNA-dependent RNA polymerase (RNAP), which is the key enzyme for the transcription process. MTB RNAP has been targeted for designing and developing antitubercular agents because gene transcription is essential for the mycobacteria survival. Initiation, elongation, and termination are the three important sequential steps in the transcription process. Each step is complex and highly regulated, involving multiple transcription factors. This review is focused on the MTB transcription machinery, especially in the nature of MTB RNAP as the main enzyme that is regulated by transcription factors. The mechanism and conformational dynamics that occur during transcription are discussed and summarized. Finally, the current progress on MTB transcription inhibition and possible drug target in mycobacterial RNAP are also described to provide insight for future antitubercular drug design and development
Office of the Children's Commissioner
The Childrenâs Commissioner, Dame Rachel de Souza, has a statutory remit to investigate the experiences of children in England. It is her duty to promote and protect the rights of all children, with particular regard to children who are living away from home or receiving social care services.
In doing this she regularly exercises her power to require government departments and other public bodies to provide administrative data, most of it at child level. The Commissionerâs research team aim to use cutting-edge methods and approaches to analysis of this data, and to triangulate findings with qualitative evidence from visits to settings such as schools, and the experiences of children the office represents directly.
This presentation will describe some of the officeâs most sensitive and innovative recent and current research. These involve the gathering, linking and analysis of admin data in youth justice, education and childrenâs social care. Examples include novel analysis published 2022 of 512 Education Health and Care Plans; text analysis of over 13 million words of police interview transcripts conducted with children, published 2023; and novel linkage of education and social care data, published 2023.
The policy context and impact of the studies will be discussed, as well as methodological challenges and opportunities for future research by the office and in partnership with other researchers
Structural Design and Synthesis of Novel Cyclic Peptide Inhibitors Targeting Mycobacterium tuberculosis Transcription
Tuberculosis (TB) remains one of the deadliest infectious diseases in the world. Although several established antitubercular drugs have been found, various factors obstruct efforts to combat this disease due to the existence of drug-resistance (DR) TB strains, the need for lengthy treatment, and the occurrence of side effects from drugâdrug interactions. Rifampicin (RIF) is the first line of antitubercular drugs and targets RNA polymerase (RNAP) of Mycobacterium tuberculosis (MTB). Here, RIF blocks the synthesis of long RNA during transcription initiation. The efficacy of RIF is low in DR-TB strains, and the use of RIF leads to various side effects. In this study, novel cyclic peptides were computationally designed as inhibitors of MTB transcription initiation. The designed cyclic peptides were subjected to a virtual screening to generate compounds that can bind to the RIF binding site in MTB RNAP subunit ÎČ (RpoB) for obtaining a new potential TB drug with a safe clinical profile. The molecular simulations showed that the cyclic peptides were capable of binding with RpoB mutants, suggesting that they can be possibility utilized for treating DR-TB. Structural modifications were carried out by acetylation and amidation of the N- and C-terminus, respectively, to improve their plasma stability and bioavailability. The modified linear and cyclic peptides were successfully synthesized with a solid-phase peptide synthesis method using Fmoc chemistry, and they were characterized by analytical HPLC, LC-ESI-MS+, and 1H NMR
Protoconch Enlargement in Western Atlantic Turritelline Gastropod Species Following the Closure of the Central American Seaway
Abstract The closure of the late Neogene interoceanic seaways between the Western Atlantic (WA) and Tropical Eastern Pacific (TEP)âcommonly referred to as the Central American Seawayâsignificantly decreased nutrient supply in the WA compared to the TEP. In marine invertebrates, an increase in parental investment is expected to be selectively favored in nutrientâpoor marine environments as prolonged feeding in the plankton becomes less reliable. Here, we examine turritelline gastropods, which were abundant and diverse across this region during the Neogene and serve as important paleoenvironmental proxies, and test whether species exhibit decreased planktotroâ phy in the WA postclosure as compared to preclosure fossils and extant TEP species. We also test for differences in degree of planktotrophy in extant sister species pairs. Degree of planktotrophy was inferred by measuring the size of protoconchs, the speâ ciesâ larval shell that represents egg size. Protoconch size was compared between extant postclosure WA and TEP species and preclosure fossil species. To compare extant sister species, we reconstructed the phylogeny of available WA and TEP speâ cies using one nuclear (H3) and three mitochondrial markers (12S, 16S, and COI). Compared to the preclosure fossils, protoconch size increased in WA species but reâ mained the same in the TEP species. In the two extant sister species pairs recovered in the phylogenetic analysis, the WA species are inferred to be nonplanktotrophic while the TEP species are planktotrophic. This suggests that decreased nutrient availâ ability and primary productivity in the WA may have driven this change in developâ mental mode, and was the primary selective force resulting in postclosure turritelline extinctions
Common Sense Recommendations for the Application of Tax Law to Digital Assets
In response to the Joint Committee on Taxationâs July 2023 request for comments on application of various Internal Revenue Code sections on digital assets, we propose a consistent set of rules to apply current law to digital assets. We highlight that the underlying economics and characteristics of transactions should be the primary concern for the application of rules and the valuation of digital assets. We believe any digital asset rules should (1) treat classes of digital assets with unique characteristics differently based on their economics, (2) minimize incentives for users to engage in tax-motivated structuring of transactions, and (3) allow the Internal Revenue Service authority to react to and regulate new classes of digital assets as they are created. We do not believe that the unique features of digital assets are a challenge to applying current law or warrant special tax preferred treatment
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
First fungal genome sequence from Africa : a preliminary analysis
Some of the most significant breakthroughs in the biological sciences this century will emerge
from the development of next generation sequencing technologies. The ease of availability
of DNA sequence made possible through these new technologies has given researchers
opportunities to study organisms in a manner that was not possible with Sanger sequencing.
Scientists will, therefore, need to embrace genomics, as well as develop and nurture the
human capacity to sequence genomes and utilise the âtsunamiâ of data that emerge from
genome sequencing. In response to these challenges, we sequenced the genome of Fusarium
circinatum, a fungal pathogen of pine that causes pitch canker, a disease of great concern to
the South African forestry industry. The sequencing work was conducted in South Africa,
making F. circinatum the first eukaryotic organism for which the complete genome has been
sequenced locally. Here we report on the process that was followed to sequence, assemble and
perform a preliminary characterisation of the genome. Furthermore, details of the computer
annotation and manual curation of this genome are presented. The F. circinatum genome was
found to be nearly 44 million bases in size, which is similar to that of four other Fusarium
genomes that have been sequenced elsewhere. The genome contains just over 15 000 open
reading frames, which is less than that of the related species, Fusarium oxysporum, but more
than that for Fusarium verticillioides. Amongst the various putative gene clusters identified
in F. circinatum, those encoding the secondary metabolites fumosin and fusarin appeared to
harbour evidence of gene translocation. It is anticipated that similar comparisons of other loci
will provide insights into the genetic basis for pathogenicity of the pitch canker pathogen.
Perhaps more importantly, this project has engaged a relatively large group of scientists
including students in a significant genome project that is certain to provide a platform for
growth in this important area of research in the future.We thank the National Research Foundation (NRF) of
South Africa, members of the Tree Protection Co-operative
Programme, the THRIP initiative of the Department of Trade
and Industry and the Department of Science and Technology
(DST)/NRF Centre of Excellence in Tree Health Biotechnology
and the Oppenheimer Foundation for funding.http://www.sajs.co.zanf201
Reflections on the 'History and Historians' of the black woman's role in the community of slaves: enslaved women and intimate partner sexual violence
Taking as points of inspiration Peter Parishâs 1989 book, Slavery: History and Historians, and Angela Davisâs seminal 1971 article, âReflections on the black womanâs role in the community of slaves,â this probes both historiographically and methodologically some of the challenges faced by historians writing about the lives of enslaved women through a case study of intimate partner violence among enslaved people in the antebellum South. Because rape and sexual assault have been defined in the past as non-consensual sexual acts supported by surviving legal evidence (generally testimony from court trials), it is hard for historians to research rape and sexual violence under slavery (especially marital rape) as there was no legal standing for the rape of enslaved women or the rape of any woman within marriage. This article suggests enslaved women recognized that black men could both be perpetrators of sexual violence and simultaneously be victims of the system of slavery. It also argues women stoically tolerated being forced into intimate relationships, sometimes even staying with âhusbandsâ imposed upon them after emancipation
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