Studies Of The Mechanism of Epidermal Injury By A Staphylococcal Epidermolytic Toxin

Experimental animal models of the two forms of toxic epidermal necrolysis have been reviewed: a murine model of staphylococcal-induced epidermolysis and a hamster model of graft-versus-host disease. In the former, a protein exotoxin, epidermolysin, has been purified and characterized. The exotoxin has a molecular weight of approximately 30,000 and causes a split beneath the granular layer. It is effective at 3 × 10-12 moles. Epidermolysin does not require an intact complement system for its action since B10D2 mice deficient in C5 or mice injected with the decomplementing agent in cobra venom factor were susceptible to its epidermolytic effects. Neither are immunocompetent thymocytes required for the action of the toxin since hairless, athymic adult (nu/nu) mice are susceptible. A few reports of epidermolysis due to an exotoxin of group I Staphylococcus aureus have appeared. This toxin is antigenically different from the exotoxin of group II organisms.A model of drug-induced toxic epidermal necrolysis has been described in hamsters, but the toxic principle released from sensitized lymphoid cells has not yet been characterized

Considerations for Improving the Capacity and Performance of AeroMACS

The Aeronautical Mobile Airport Communications System (AeroMACS) has progressed from concept through prototype development, testing, and standards development and is now poised for the first operational deployments at nine US airports by the Federal Aviation Administration. These initial deployments will support fixed applications. Mobile applications providing connectivity to and from aircraft and ground-based vehicles on the airport surface will occur at some point in the future. Given that many fixed applications are possible for AeroMACS, it is necessary to now consider whether the existing capacity of AeroMACS will be reached even before the mobile applications are ready to be added, since AeroMACS is constrained by both available bandwidth and transmit power limitations. This paper describes some concepts that may be applied to improve the future capacity of AeroMACS, with a particular emphasis on gains that can be derived from the addition of IEEE 802.16j multihop relays to the AeroMACS standard, where a significant analysis effort has been undertaken

Developing and evaluating mental health lived experience practitioner (LXP) roles in an NHS trust

The value of establishing roles for people with lived experience of mental distress within mental health services is increasingly being recognised. However, there is limited information to guide the introduction of these roles into mental health services. This study details the development and evaluation of a new mental health peer worker role, the Lived Experience Practitioner (LXP), within an NHS Trust. A three-phase exploratory mixed-methods approach was used. Qualitative data were collected and analysed in the first phase. The qualitative findings were then translated into the formal procedures for introducing LXPs into the Trust, with the approach examined quantitatively in the third phase. The qualitative analysis identified five themes; role design, training, piloting, career pathways and communication. These formed the basis for working groups (workstreams) which developed policies and procedures for introducing the LXP role into the Trust. Twenty-eight applicants commenced a training programme with 10 successful completions. Seven LXPs were employed by the Trust and were still in their posts after 2 years. In this study, three areas were viewed as important when introducing LXP roles into mental health services; organisational support, the training programme and employment procedures

TB113: A Field Test of Mating-Suppression Using the Spruce Budworm Sex Pheromone

Spruce budworm sex pheromone was dispersed from aircraft over forest land in Maine in late June, 1980. A major goal was to sample pheromone concentrations in air to determine whether the formulation would provide the steady, sustained release of chemical believed required for interfering with the mating process of the moths. Since pheromone was going to be applied for purposes of analyses of air, we believed we should also study some behavioral effects on spruce budworm populations. The principal body of data involved the ability of male budworm moths to orient to point sources of pheromone in pheromone-treated and untreated forest blocks, but attempts were also made to monitor fertility levels among females and to measure populations of eggs.https://digitalcommons.library.umaine.edu/aes_techbulletin/1073/thumbnail.jp

SCPS-TP, TCP, and Rate-Based Protocol Evaluation

Tests were performed at Glenn Research Center to compare the performance of the Space Communications Protocol Standard Transport Protocol (SCPS TP, otherwise known as "TCP Tranquility") relative to other variants of TCP and to determine the implementation maturity level of these protocols, particularly for higher speeds. The testing was performed over reasonably high data rates of up to 100 Mbps with delays that are characteristic of near-planetary environments. The tests were run for a fixed packet size, but for variously errored environments. This report documents the testing performed to date

The methyl binding domain 3/nucleosome remodelling and deacetylase complex regulates neural cell fate determination and terminal differentiation in the cerebral cortex.

BACKGROUND: Chromatin-modifying complexes have key roles in regulating various aspects of neural stem cell biology, including self-renewal and neurogenesis. The methyl binding domain 3/nucleosome remodelling and deacetylation (MBD3/NuRD) co-repressor complex facilitates lineage commitment of pluripotent cells in early mouse embryos and is important for stem cell homeostasis in blood and skin, but its function in neurogenesis had not been described. Here, we show for the first time that MBD3/NuRD function is essential for normal neurogenesis in mice. RESULTS: Deletion of MBD3, a structural component of the NuRD complex, in the developing mouse central nervous system resulted in reduced cortical thickness, defects in the proper specification of cortical projection neuron subtypes and neonatal lethality. These phenotypes are due to alterations in PAX6+ apical progenitor cell outputs, as well as aberrant terminal neuronal differentiation programmes of cortical plate neurons. Normal numbers of PAX6+ apical neural progenitor cells were generated in the MBD3/NuRD-mutant cortex; however, the PAX6+ apical progenitor cells generate EOMES+ basal progenitor cells in reduced numbers. Cortical progenitor cells lacking MBD3/NuRD activity generate neurons that express both deep- and upper-layer markers. Using laser capture microdissection, gene expression profiling and chromatin immunoprecipitation, we provide evidence that MBD3/NuRD functions to control gene expression patterns during neural development. CONCLUSIONS: Our data suggest that although MBD3/NuRD is not required for neural stem cell lineage commitment, it is required to repress inappropriate transcription in both progenitor cells and neurons to facilitate appropriate cell lineage choice and differentiation programmes.We wish to thank Nicola Reynolds for the help with figures; Aoife O’Shaughnessy for the critical reading of the manuscript; Peter Humphreys, the SCI Biofacility staff and Margaret McLeish for technical assistance; Stephanie Hall and Gerard Evan for access to the Laser Capture Microscope and Nathalie Saurat and members of the BH lab for useful discussions. This work was supported by a Wellcome Trust Senior Fellowship in the Basic Biomedical Sciences awarded to BH and a bourse de formation from the Fonds de la Recherche en Santé Québec awarded to EK.This is the final published version of the article. It was originally published in Neural Development (Knock E, et al., Neural Development, 2015, 10:13, doi:10.1186/s13064-015-0040-z). The final version is available at http://dx.doi.org/10.1186/s13064-015-0040-

Transposon Mutagenesis in Chlamydia trachomatis Identifies CT339 as a ComEC Homolog Important for DNA Uptake and Lateral Gene Transfer

Transposon mutagenesis is a widely applied and powerful genetic tool for the discovery of genes associated with selected phenotypes. Chlamydia trachomatis is a clinically significant, obligate intracellular bacterium for which many conventional genetic tools and capabilities have been developed only recently. This report describes the successful development and application of a Himar transposon mutagenesis system for generating single-insertion mutant clones of C. trachomatis. This system was used to generate a pool of 105 transposon mutant clones that included insertions in genes encoding flavin adenine dinucleotide (FAD)-dependent monooxygenase (C. trachomatis 148 [ct148]), deubiquitinase (ct868), and competence-associated (ct339) proteins. A subset of Tn mutant clones was evaluated for growth differences under cell culture conditions, revealing that most phenocopied the parental strain; however, some strains displayed subtle and yet significant differences in infectious progeny production and inclusion sizes. Bacterial burden studies in mice also supported the idea that a FAD-dependent monooxygenase (ct148) and a deubiquitinase (ct868) were important for these infections. The ct339 gene encodes a hypothetical protein with limited sequence similarity to the DNA-uptake protein ComEC. A transposon insertion in ct339 rendered the mutant incapable of DNA acquisition during recombination experiments. This observation, along with in situ structural analysis, supports the idea that this protein is playing a role in the fundamental process of lateral gene transfer similar to that of ComEC. In all, the development of the Himar transposon system for Chlamydia provides an effective genetic tool for further discovery of genes that are important for basic biology and pathogenesis aspects.S.D.L., Z.E.D., K.S.H., S.B., R.J.S., and P.S.H. were funded by NIH (AI126785)J.W. and P.S.H. were supported by NIH AI125929. P.S.H. was also supported by P20GM113117Support for genomic sequencing was supplemented by P20GM10363

Structural and ligand binding analyses of the periplasmic sensor domain of RsbU in Chlamydia trachomatis support a role in TCA cycle regulation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154297/1/mmi14401-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154297/2/mmi14401_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154297/3/mmi14401.pd

Inclusion at Scale: Deploying a Community-Driven Moderation Intervention on Twitch

Harassment, especially of marginalized individuals, on networked gaming and social media platforms has been identified as a significant issue, yet few HCI practitioners have attempted to create interventions tackling toxicity online. Aligning ourselves with the growing cohort of design activists, we present a case study of the GLHF pledge, an interactive public awareness campaign promoting positivity in video game live streaming. We discuss the design and deployment of a community-driven moderation intervention for GLHF, intended to empower the inclusive communities emerging on Twitch. After offering a preliminary report on the effects we have observed based on the more than 370,000 gamers who have participated to date, the paper concludes with a reflection on the challenges and opportunities of using design activism to positively intervene in large-scale media platforms

Percutaneous coronary revascularization in patients with formerly "refractory angina pectoris in end-stage coronary artery disease" – Not "end-stage" after all

<p>Abstract</p> <p>Background</p> <p>Patients with refractory angina pectoris in end-stage coronary artery disease represent a severe condition with a higher reduction of life-expectancy and quality of life as compared to patients with stable coronary artery disease. It was the purpose of this study to invasively re-evaluate highly symptomatic patients with formerly diagnosed refractory angina pectoris in end-stage coronary artery disease for feasible options of myocardial revascularization.</p> <p>Methods</p> <p>Thirty-four Patients formerly characterized as having end stage coronary artery disease with refractory angina pectoris were retrospectively followed for coronary interventions.</p> <p>Results</p> <p>Of those 34 patients 21 (61.8%) were eventually revascularized with percutaneous interventional revascularization (PCI). Due to complex coronary morphology (angulation, chronic total occlusion) PCI demanded an above-average amount of time (66 ± 42 minutes, range 25–206 minutes) and materials (contrast media 247 ± 209 ml, range 50–750 ml; PCI guiding wires 2.0 ± 1.4, range 1–6 wires). Of PCI patients 7 (33.3%) showed a new lesion as a sign of progression of atherosclerosis. Clinical success rate with a reduction to angina class II or lower was 71.4% at 30 days. Surgery was performed in a total of8 (23.5%) patients with a clinical success rate of 62.5%. Based on an intention-to-treat 2 patients of originally 8 (25%) demonstrated clinical success. Mortality during follow-up (1–18 months) was 4.8% in patients who underwent PCI, 25% in patients treated surgically and 25% in those only treated medically.</p> <p>Conclusion</p> <p>The majority of patients with end-stage coronary artery disease can be treated effectively with conventional invasive treatment modalities. Therefore even though it is challenging and demanding PCI should be considered as a first choice before experimental interventions are considered.</p