Tortures, Jealousy Tests and Getting Tough

I tortured Jenny Little, now an actress in London, with the Chinese burn. Telephone Jenny Little in East Sheen and ask her if she remembers being tortured at Nowra Infants School near the Headmistress\u27s garden with the Chinese burn. The garden where you found nuts you could shoot at each other\u27s eyes with your thumb. Along from the trees which at the right time of the year provided the rough nuts on the end of a stalk, a blow from which could cause a headache. Or if these were out of season, you could roll your handkerchief and twist it into a cosh which each year had to be banned because of headaches. You had to be careful or the girls would hold you down and kiss you

TF Target Mapper: A BLAST search tool for the identification of Transcription Factor target genes

BACKGROUND: In the current era of high throughput genomics a major challenge is the genome-wide identification of target genes for specific transcription factors. Chromatin immunoprecipitation (ChIP) allows the isolation of in vivo binding sites of transcription factors and provides a powerful tool for examining gene regulation. Crosslinked chromatin is immunoprecipitated with antibodies against specific transcription factors, thus enriching for sequences bound in vivo by these factors in the immunoprecipitated DNA. Cloning and sequencing the immunoprecipitated sequences allows identification of transcription factor target genes. Routinely, thousands of such sequenced clones are used in BLAST searches to map their exact location in the genome and the genes located in the vicinity. These genes represent potential targets of the transcription factor of interest. Such bioinformatics analysis is very laborious if performed manually and for this reason there is a need for developing bioinformatic tools to automate and facilitate it. RESULTS: In order to facilitate this analysis we generated TF Target Mapper (Transcription Factor Target Mapper). TF Target Mapper is a BLAST search tool allowing rapid extraction of annotated information on genes around each hit. It combines sequence cleaning/filtering, pattern searching and BLAST searches with extraction of information on genes located around each BLAST hit and comparisons of the output list of genes or gene ontology IDs with user-implemented lists. We successfully applied and tested TF Target Mapper to analyse sequences bound in vivo by the transcription factor GATA-1. We show that TF Target Mapper efficiently extracted information on genes around ChIPed sequences, thus identifying known (e.g. α-globin and ζ-globin) and potentially novel GATA-1 gene targets. CONCLUSION: TF Target Mapper is a very efficient BLAST search tool that allows the rapid extraction of annotated information on the genes around each hit. It can contribute to the comprehensive bioinformatic transcriptome/regulome analysis, by providing insight into the mechanisms of action of specific transcription factors, thus helping to elucidate the pathways these factors regulate

G3DV: A new 3D genome browser and experimental data viewer.

Genomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of information. Their system-biological complexity remains, however, still largely mysterious, despite immense sequencing achievements and huge advances in the understanding of the general sequential, three-dimensional and regulatory organization. Here, we present the GLOBE 3D Genome Platform a completely novel grid based virtual “paper” tool and in fact the first system-biological genome browser integrating the holistic complexity of genomes in a single easy comprehensible platform: Based on a detailed study of biophysical and IT requirements, every architectural level from sequence to morphology of one or several genomes can be approached in a real and in a symbolic representation simultaneously and navigated by continuous scale-free zooming within a unique three-dimensional OpenGL and grid driven environment. In principle an unlimited number of multi-dimensional data sets can be visualized, customized in terms of arrangement, shape, colour, and texture etc. as well as accessed and annotated individually or in groups using internal or external data bases/facilities. Any information can be searched and correlated by importing or calculating simple relations in real-time using grid resources. A general correlation and application platform for more complex correlative analysis and a front-end for system-biological simulations both using again the huge capabilities of grid infrastructures is currently under development. Hence, the GLOBE 3D Genome Platform is an example of a grid based approach towards a virtual desktop for genomic work combining the three fundamental distributed resources: i) visual data representation, ii) data access and management, and iii) data analysis and creation. Thus, the GLOBE 3D Genome Platform is the novel system-biology oriented information system urgently needed to access, present, annotate, and to simulate the holistic genome complexity in a unique gateway towards a real understanding, educative presentation and curative manipulation planning of this tremendous evolutionary information grail – genomes

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Excerpt: \u27The Diplomacy of Bibulation\u27

This is the first published extract from a yet untitled novel, which is the sequel to Frank Moorhouse’s book Grand Days (Pantheon, 1994). The sequel is set in Geneva at the League of Nations in the ]930s. Edith, an Australian woman, works in the Secretariat of the League. She is married to a journalist, Robert Dole, who is away covering Japan’s invasion of China. Meanwhile, her somewhat unorthodox lover, Ambrose, a former English diplomat, now disgraced, who now works in an international organization with its offices in Geneva, has, at her invitation, moved into the apartment. Edith is struggling to make her career as a diplomat at the League. The year is 1935, and, in mid career, Edith blunders

Frank Moorhouse interviewed by Suzanne Hayes

While at the Adelaide Festival of Arts in 1980, Australian author Frank Moorhouse spoke with Suzanne Hayes of the Adelaide college of Technical and Further Education (TAFE) about his techniques in fiction, the subject matter of his first four works of fiction, his attitude to expatriate authors and other aspects of his writing life

Freedom of expression bound and gagged

In The writer in a time of terror - the first comprehensive review of the consequences of enforcing anti terror laws which restrict freedom of expression - Frank Moorhouse reveals a chilling portrait of a new authoritarianism. While researching this major essay for Griffith REVIEW, Frank traces a pattern of over a dozen recent events, including book banning, raids on media offices, and "cleansing" manuscripts deemed to be threats to national security. He discovers "The rule is that lower codes of civil liberty inevitably do grave damage to innocent people, by design, by accident or by abuse." He argues that censorship diminishes the citizen while increasing the threat of terrorism, and contends "We should try to be just and humane in our conduct towards our perceived enemies and our real enemies, regardless of their behaviour and standards." Includes excerpts from the latest banned books

Manifesto for the imagination

Frank explores the importance and fragility of the imagination and the dangers of heavy handed interventions. "Because of the Henson controversy, I decided I should sit down and look at the reasoning we use to defend the faculty of the artistic imagination: why is the artistic imagination treated as a thing of angry suspicion and distaste by some people and with awe by others; from where does the imagination claim its authority to challenge conventions and the law?