Adding Spin Functionality to Traditional Optoelectronics via Chiral Perovskite

Spin polarized current generation and injection into semiconductors at room temperature are key to enable a broader range of opto-spintronic functionalities, yet the inherent efficiency of spin injection across commonly used semiconductor-ferromagnet interfaces is limited. Here, we demonstrate efficient spin injection into commercially viable III-V light emitting diodes (LED) by integrating chiral halide perovskite layers with (AlxGa1-x)0.5In0.5P multiple quantum wells (MQW). Spin polarized current is injected via chirality induced spin selectivity (CISS) and the spin accumulation in the III-V semiconductor is detected via the emission of circularly polarized light with a degree of circular polarization of up to ~ 15%. X-ray photoemission spectroscopy (XPS) and transmission electron microscopy (TEM) cross sectional imaging indicate a pristine perovskite/III-V interface. These findings demonstrate chiral perovskite semiconductors transform well-developed semiconductor platforms to enable control over spin, charge, and light

Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Hypoxia has been associated with poor local tumour control and relapse in many cancer sites, including carcinoma of the prostate. This translational study tests whether breathing carbogen gas improves the oxygenation of human prostate carcinoma xenografts in mice and in human patients with prostate cancer. A total of 23 DU145 tumour-bearing mice, 17 PC3 tumour-bearing mice and 17 human patients with prostate cancer were investigated. Intrinsic susceptibility-weighted MRI was performed before and during a period of carbogen gas breathing. Quantitative R2* pixel maps were produced for each tumour and at each time point and changes in R2* induced by carbogen were determined. There was a mean reduction in R2* of 6.4% (P=0.003) for DU145 xenografts and 5.8% (P=0.007) for PC3 xenografts. In all, 14 human subjects were evaluable; 64% had reductions in tumour R2* during carbogen inhalation with a mean reduction of 21.6% (P=0.0005). Decreases in prostate tumour R2* in both animal models and human patients as a result of carbogen inhalation suggests the presence of significant hypoxia. The finding that carbogen gas breathing improves prostate tumour oxygenation provides a rationale for testing the radiosensitising effects of combining carbogen gas breathing with radiotherapy in prostate cancer patients

Single Honeybee Silk Protein Mimics Properties of Multi-Protein Silk

Honeybee silk is composed of four fibrous proteins that, unlike other silks, are readily synthesized at full-length and high yield. The four silk genes have been conserved for over 150 million years in all investigated bee, ant and hornet species, implying a distinct functional role for each protein. However, the amino acid composition and molecular architecture of the proteins are similar, suggesting functional redundancy. In this study we compare materials generated from a single honeybee silk protein to materials containing all four recombinant proteins or to natural honeybee silk. We analyse solution conformation by dynamic light scattering and circular dichroism, solid state structure by Fourier Transform Infrared spectroscopy and Raman spectroscopy, and fiber tensile properties by stress-strain analysis. The results demonstrate that fibers artificially generated from a single recombinant silk protein can reproduce the structural and mechanical properties of the natural silk. The importance of the four protein complex found in natural silk may lie in biological silk storage or hierarchical self-assembly. The finding that the functional properties of the mature material can be achieved with a single protein greatly simplifies the route to production for artificial honeybee silk

Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma

Eumycetoma is a chronic infectious disease characterized by a large subcutaneous mass, often caused by the fungus Madurella mycetomatis. A combination of surgery and prolonged medication is needed to treat this infection with a success rate of only 30%. There is, the

Criteria for the use of omics-based predictors in clinical trials: Explanation and elaboration

High-throughput 'omics' technologies that generate molecular profiles for biospecimens have been extensively used in preclinical studies to reveal molecular subtypes and elucidate the biological mechanisms of disease, and in retrospective studies on clinical specimens to develop mathematical models to predict clinical endpoints. Nevertheless, the translation of these technologies into clinical tests that are useful for guiding management decisions for patients has been relatively slow. It can be difficult to determine when the body of evidence for an omics-based test is sufficiently comprehensive and reliable to support claims that it is ready for clinical use, or even that it is ready for definitive evaluation in a clinical trial in which it may be used to direct patient therapy. Reasons for this difficulty include the exploratory and retrospective nature of many of these studies, the complexity of these assays and their application to clinical specimens, and the many potential pitfalls inherent in the development of mathematical predictor models from the very high-dimensional data generated by these omics technologies. Here we present a checklist of criteria to consider when evaluating the body of evidence supporting the clinical use of a predictor to guide patient therapy. Included are issues pertaining to specimen and assay requirements, the soundness of the process for developing predictor models, expectations regarding clinical study design and conduct, and attention to regulatory, ethical, and legal issues. The proposed checklist should serve as a useful guide to investigators preparing proposals for studies involving the use of omics-based tests. The US National Cancer Institute plans to refer to these guidelines for review of proposals for studies involving omics tests, and it is hoped that other sponsors will adopt the checklist as well. © 2013 McShane et al.; licensee BioMed Central Ltd

Inhibiting DHN- and DOPA-melanin biosynthesis pathway increased the therapeutic value of itraconazole in Madurella mycetomatis infected Galleria mellonella

Eumycetoma is a neglected tropical disease, and Madurella mycetomatis, the most common causative agent of this disease forms black grains in hosts. Melanin was discovered to be one of the constituents in grains. Melanins are hydrophobic, macromolecular pigments formed by oxidative polymerisation of phenolic or indolic compounds. M. mycetomatis was previously known to produce DHN-melanin and pyomelanin in vitro. These melanin was also discovered to decrease M. mycetomatis's susceptibility to antifungals itraconazole and ketoconazole in vitro. These findings, however, have not been confirmed in vivo. To discover the melanin biosynthesis pathways used by M. mycetomatis in vivo and to determine if inhibiting melanin production would increase M. mycetomatis's susceptibility to itraconazole, inhibitors targeting DHN-, DOPA- and pyomelanin were used. Treatment with DHN-melanin inhibitors tricyclazole, carpropamid, fenoxanil and DOPA-melanin inhibitor glyphosate in M. mycetomatis infected Galleria mellonella larvae resulted in presence of non-melanized grains. Our finding suggested that M. mycetomatis is able to produce DOPA-melanin in vivo. Inhibiting DHN-melanin with carpropamid in combination with the antifungal itraconazole also significantly increased larvae survival. Our results suggested that combination treatment of antifungals and melanin inhibitors can be an alternative treatment strategy that can be further explored. Since the common black-grain eumycetoma causing agents uses similar melanin biosynthesis pathways, this strategy may be applied to them and other eumycetoma causative agents. LAY SUMMARY: Melanin protects fungi from environmental stress and antifungals. We have discovered that Madurella mycetomatis produces DHN-, pyomelanin and DOPA-melanin in vivo. Inhibiting M. mycetomatis DHN-melanin biosynthesis increases therapeutic value of the antifungal itraconazole in vivo

Connection and Disconnection: Encounters between Settlers and Indigenous People in the Northern Territory

'Connection and Disconnection' brings together twelve historians with an interest in encounters between Indigenous people and settlers in the Northern Territory. More than just a narrative of conflict and dispossession, the volume is concerned to reconceptualise the present through the past, rather than just understand the past itself. Chapters deal with a range of encounters which bring new light to bear on the relationships between people on the northern frontier - some of them positive. The volume includes new interpretations of sites of dispossession and war, together with accounts of the sometimes successful struggle by settlers to develop an understanding of Aboriginal people and cultures; well-meaning but frequently misguided attempts to provide for the welfare of Aboriginal people; and usually unsuccessful efforts by authorities to divest the people of their Aboriginality. The book will be of interest to all readers seeking to understand the circumstances that have made reconciliation such a key issue in our national identity as we approach the new millennium.Introduction. An overview : Two centuries of contact / Suzanne Parry and Tony Austin -- 1. The British meet the Tiwi : Melville island, 1824 / JMR Cameron -- 2. Gillen time: The creation of an era / Richard Kimber -- 3. Police trackers : Myth and reality / Bill Wilson -- 4. Rationing's moral economy / Tim Rowse -- 5. Discourse and disclosure : The Daly River outrage / Michael F. Christie -- 6. A bag of lollies : Children as mediators in the Northern Territory / Lyn Riddett -- 7. The literary construction of 'Half-caste' in the 1930's : Gender, sexuality and race in the Northern Territory / Mickey Dewar -- 8. The dispossession of the Warumungu : Encounters on a North Australian mining frontier / David Carment -- 9. Taming the Yolngu : Methodists, race and schooling in Arnhem land 1916-1939 / Tony Austin -- 10. Mission endeavour : The impact of Christian missions on Aboriginal health / Suzanne Parry -- 11. Welfare colonialists : Context and encounters on government settlements / Julie T. Wells -- 12. The implementation of government funded Aboriginal education in the Northern Territory 1949 to 1955 / Margot Ford.Jira Ticket : CDU-59 : Collection Development Manager made the decision that for the books that have this message " This book is copyright. Apart from any fair dealing to the purpose of private study, research, criticism or review as permitted under the Copyright Act, no part may be reproduced, by any process, without written permission. Enquiries should be made to the publisher, Charles Darwin University Press, Charles Darwin University, Darwin NT 0909, Australia" in the front they would treat CDU NTU Press as the copyright holder based on this statement. CDU Press have given permission for these to be added to our site but no additional licencing terms provided. That is a reasonable risk management based decision

Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma

<div><p>Eumycetoma is a chronic infectious disease characterized by a large subcutaneous mass, often caused by the fungus <i>Madurella mycetomatis</i>. A combination of surgery and prolonged medication is needed to treat this infection with a success rate of only 30%. There is, therefore, an urgent need to find more effective drugs for the treatment of this disease. In this study, we screened 800 diverse drug-like molecules and identified 215 molecules that were active <i>in vitro</i>. Minimal inhibitory concentrations were determined for the 13 most active compounds. One of the most potent compounds, a fenarimol analogue for which a large analogue library is available, led to the screening of an additional 35 compounds for their <i>in vitro</i> activity against <i>M</i>. <i>mycetomatis</i> hyphae, rendering four further hit compounds. To assess the <i>in vivo</i> potency of these hit compounds, a <i>Galleria mellonella</i> larvae model infected with <i>M</i>. <i>mycetomatis</i> was used. Several of the compounds identified <i>in vitro</i> demonstrated promising efficacy <i>in vivo</i> in terms of prolonged larval survival and/or reduced fungal burden. The results presented in this paper are the starting point of an <i>Open Source Mycetoma (MycetOS)</i> approach in which members of the global scientific community are invited to participate and contribute as equal partners. We hope that this initiative, coupled with the promising new hits we have reported, will lead to progress in drug discovery for this most neglected of neglected tropical diseases.</p></div

Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma - Fig 4

<p>A) 2-D Chemical space representation of the 800 member fenarimol analogue library. X -axis represents a Principal Component Analysis of approximately 100 different physichochemical properties, Y-axis represents a Principal Component Analysis of 1024 Morgan chemical fingerprints (all calculations performed using RDKit in KNIME)[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006437#pntd.0006437.ref052" target="_blank">52</a>] Compounds chosen for test are represented by oversized points, and different core scaffolds represented by colour (Blue -scaffold A; green scaffold B, red scaffold C, yellow scaffold D). B: % Growth inhibition by selected fenarimol analogues at 25 and 100 μM. Percentage growth was calculated using the following formula: (E_sample-E_nc)/(E_gc-E_nc)*100%.</p