Determination of cardiac size from chest roentgenograms following Skylab missions

Decreased cardiothoracic transverse diameter ratios following Mercury, Gemini and Apollo space flights have been reported previously. To evaluate further changes in cardiac size, standard posteroanterior chest films in systole and diastole were obtained before flight and within a few hours after recovery on each of the Skylab astronauts. Postflight chest X-rays were visually compared to the preflight roentgenograms for possible changes in pulmonary vasculature, lung parenchyma, bony or soft tissue structures. From these roentgenograms the following measurements were obtained: cardiac and thoracic transverse diameters, cardiothoracic transverse diameter ratio, cardiac area from the product of both diagonal diameters, cardiac silhouette area by planimetry, thoracic cage area and cardiothoracic area ratio. The postflight frontal cardiac silhouette sizes were significantly decreased when compared with the respective preflight values (P0.05 or 0.01). The observed changes are thought to be related to postflight decrease in the intracardiac chamber volume

Beryllium fastener technology

Program was conducted to develop, produce, and test optimum-configuration, beryllium prestressed and blind fasteners. The program was carried out in four phases - phase 1, feasibility study, phase 2, development, phase 3, evaluation of beryllium alloys, and phase 4, fabrication and testing

Water monitoring with hyperspectral techniques

1 - The poor of the world depends directly on water and other natural resources for their livelihoods. Water resources must therefore be managed in a sustainable manner in order to maintain the economic, social and environmental functions and to contribute to the livelihoods of people. 2 - Advancements in sensor technologies and processing algorithms have resulted in technical capabilities that can record and identify Earth surface materials based on the interaction of electromagnetic energy with the molecular structure of the material being sensed. 3 - Non-destructive and operative methodologies (NIR and Raman) will be tested through field surveys and laboratory analysis using Aquaphotomics approach. This approach requires precise measuring and mapping capabilities at field level of key data at a sufficient level of accuracy depending on the availability of equipment that must be also operated at a cost-effective way

SLC19A1 transports immunoreactive cyclic dinucleotides.

The accumulation of DNA in the cytosol serves as a key immunostimulatory signal associated with infections, cancer and genomic damage1,2. Cytosolic DNA triggers immune responses by activating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway3. The binding of DNA to cGAS activates its enzymatic activity, leading to the synthesis of a second messenger, cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP)4-7. This cyclic dinucleotide (CDN) activates STING8, which in turn activates the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), promoting the transcription of genes encoding type I interferons and other cytokines and mediators that stimulate a broader immune response. Exogenous 2'3'-cGAMP produced by malignant cells9 and other CDNs, including those produced by bacteria10-12 and synthetic CDNs used in cancer immunotherapy13,14, must traverse the cell membrane to activate STING in target cells. How these charged CDNs pass through the lipid bilayer is unknown. Here we used a genome-wide CRISPR-interference screen to identify the reduced folate carrier SLC19A1, a folate-organic phosphate antiporter, as the major transporter of CDNs. Depleting SLC19A1 in human cells inhibits CDN uptake and functional responses, and overexpressing SLC19A1 increases both uptake and functional responses. In human cell lines and primary cells ex vivo, CDN uptake is inhibited by folates as well as two medications approved for treatment of inflammatory diseases, sulfasalazine and the antifolate methotrexate. The identification of SLC19A1 as the major transporter of CDNs into cells has implications for the immunotherapeutic treatment of cancer13, host responsiveness to CDN-producing pathogenic microorganisms11 and-potentially-for some inflammatory diseases

Effects of bovine parathyroid hormone and 1,25-dihydroxyvitamin D3 on the production of prostaglandins by cells derived from human bone

AbstractLocal production of prostaglandins by osteoblasts may be important in controlling the bone resorbing activity of some hormones which have receptors on osteoblasts. We have demonstrated that osteoblast-like cells derived from human bone can incorporate [14C]arachidonic acid into phospholipids and synthesise immunoreactive PGE. Parathyroid hormone increases both the release of incorporated arachidonic acid and the synthesis of PGE. This is the first demonstration of modulation of bone cell prostaglandin synthesis by a bone resorbing hormone

Upper- and lower-limb amputees show reduced levels of eeriness for images of prosthetic hands

The uncanny phenomenon describes the feeling of unease associated with seeing an image which is close to appearing human. Prosthetic hands in particular are well-known to induce this effect. Little is known, however, about this phenomenon from the viewpoint of prosthesis users. We studied perceptions of eeriness and human-likeness for images of different types of mechanical, cosmetic, and anatomical hands in upper-limb prosthesis users (n=9), lower-limb prosthesis users (n=10), prosthetists (n=16), control participants with no prosthetic training (n=20), and control participants who were trained to use a myoelectric prosthetic hand simulator (n=23). Both the upper- and lowerlimb prosthesis user groups showed a reduced uncanny phenomenon (i.e., significantly lower levels of eeriness) for cosmetic prosthetic hands compared to the other groups, with no concomitant reduction in how these stimuli were rated in terms of human-likeness. However, a similar effect was found neither for prosthetists with prolonged visual experience of prosthetic hands, nor for the group with short-term training with the simulator. These findings in the prosthesis users therefore seem likely to be related to limb absence or prolonged experience with prostheses

Climate Clever Beef : On-farm demonstration of adaptation and mitigation options for climate change in northern Australia

This project engaged with beef producers in five regions of northern Australia to identify management options that improve the performance and resilience of beef businesses. The work was done in the context of increasing the resilience of businesses to current climate variability as well as to projected changes in climate. The project also identified potential synergies and conflicts between improved business performance, climate adaptation practices and greenhouse gas emissions management. Three regions (Qld Gulf, Fitzroy Basin and Victoria River District) evaluated climate adaptation and greenhouse gas mitigation options via a benchmarking and options analysis approach with three “focal” properties. Five indicators of performance were evaluated for each property – profitability, productivity, land condition, climate change risk and greenhouse gas emissions. These detailed business analyses were complemented by demonstration sites in each region. Two other regions (Qld Mitchell grasslands and NT Barkly Tablelands) used on-property demonstration sites to showcase promising climate adaptation practices identified in a previous project. The focal property approach provided a systematic process for assessing current business performance as well as a ready means of estimating the impacts of management changes. For example, over a 15 year period, the Qld Gulf focal property improved its pasture condition dramatically by stocking around the long-term carrying capacity and undertaking wet season spelling. This, combined with herd management improvements, increased profitability and productivity, reduced greenhouse gas emissions by 15%, and improved greenhouse gas emission efficiency by >100%. The demonstration sites in each region effectively promoted and documented the benefits of key grazing practices for improving resilience to both current climate variability and potential climate change. For example, on a 16,118km² property in the Barkly, a paddock demonstration has documented initial land condition recovery at old bores, and the reduced risk of overgrazing around new bores, through best practice stocking rate management and wet season spelling. Qualitative analyses showed that many of the adaptation practices identified for improving resilience are consistent with existing best practice recommendations aimed at improving productivity and sustainability. Furthermore, these adaptation practices appear to have largely neutral implications for greenhouse gas emissions. In contrast, practices and options for reducing greenhouse gas emissions were more likely to create conflicts that leave enterprises more vulnerable to climate change. Examples of the negative consequences of mitigation measures include reduced pasture production associated with increased carbon sequestration in trees (i.e. woody vegetation thickening or regrowth retention) and increased operating costs associated with carbon pricing (if these are not offset with carbon credits). The project demonstration sites and focal property benchmarking process provided a solid base for focussed extension work targeting the drivers of profit, land condition, greenhouse gas emissions intensity and climate adaptation strategies

Assessing changes in vascular permeability in a hamster model of viral hemorrhagic fever

<p>Abstract</p> <p>Background</p> <p>A number of RNA viruses cause viral hemorrhagic fever (VHF), in which proinflammatory mediators released from infected cells induce increased permeability of the endothelial lining of blood vessels, leading to loss of plasma volume, hypotension, multi-organ failure, shock and death. The optimal treatment of VHF should therefore include both the use of antiviral drugs to inhibit viral replication and measures to prevent or correct changes in vascular function. Although rodent models have been used to evaluate treatments for increased vascular permeability (VP) in bacterial sepsis, such studies have not been performed for VHF.</p> <p>Results</p> <p>Here, we use an established model of Pichinde virus infection of hamsters to demonstrate how changes in VP can be detected by intravenous infusion of Evans blue dye (EBD), and compare those measurements to changes in hematocrit, serum albumin concentration and serum levels of proinflammatory mediators. We show that EBD injected into sick animals in the late stage of infection is rapidly sequestered in the viscera, while in healthy animals it remains within the plasma, causing the skin to turn a marked blue color. This test could be used in live animals to detect increased VP and to assess the ability of antiviral drugs and vasoactive compounds to prevent its onset. Finally, we describe a multiplexed assay to measure levels of serum factors during the course of Pichinde arenavirus infection and demonstrate that viremia and subsequent increase in white blood cell counts precede the elaboration of inflammatory mediators, which is followed by increased VP and death.</p> <p>Conclusions</p> <p>This level of model characterization is essential to the evaluation of novel interventions designed to control the effects of virus-induced hypercytokinemia on host vascular function in VHF, which could lead to improved survival.</p

A Forward Genetic Screen Reveals Novel Independent Regulators of Ulbp1, an Activating Ligand for Natural Killer Cells

Recognition and elimination of tumor cells by the immune system is crucial for limiting tumor growth. Natural killer (NK) cells become activated when the receptor NKG2D is engaged by ligands that are frequently upregulated in primary tumors and on cancer cell lines. However, the molecular mechanisms driving NKG2D ligand expression on tumor cells are not well defined. Using a forward genetic screen in a tumor-derived human cell line, we identified several novel factors supporting expression of the NKG2D ligand ULBP1. Our results show stepwise contributions of independent pathways working at multiple stages of ULBP1 biogenesis. Deeper investigation of selected hits from the screen showed that the transcription factor ATF4 drives ULBP1 gene expression in cancer cell lines, while the RNA-binding protein RBM4 supports ULBP1 expression by suppressing a novel alternatively spliced isoform of ULBP1 mRNA. These findings offer insight into the stress pathways that alert the immune system to danger

Feature Fusion of Raman Chemical Imaging and Digital Histopathology using Machine Learning for Prostate Cancer Detection

The diagnosis of prostate cancer is challenging due to the heterogeneity of its presentations, leading to the over diagnosis and treatment of non-clinically important disease. Accurate diagnosis can directly benefit a patient’s quality of life and prognosis. Towards addressing this issue, we present a learning model for the automatic identification of prostate cancer. While many prostate cancer studies have adopted Raman spectroscopy approaches, none have utilised the combination of Raman Chemical Imaging (RCI) and other imaging modalities. This study uses multimodal images formed from stained Digital Histopathology (DP) and unstained RCI. The approach was developed and tested on a set of 178 clinical samples from 32 patients, containing a range of non-cancerous, Gleason grade 3 (G3) and grade 4 (G4) tissue microarray samples. For each histological sample, there is a pathologist labelled DP - RCI image pair. The hypothesis tested was whether multimodal image models can outperform single modality baseline models in terms of diagnostic accuracy. Binary non-cancer/cancer models and the more challenging G3/G4 differentiation were investigated. Regarding G3/G4 classification, the multimodal approach achieved a sensitivity of 73.8% and specificity of 88.1% while the baseline DP model showed a sensitivity and specificity of 54.1% and 84.7% respectively. The multimodal approach demonstrated a statistically significant 12.7% AUC advantage over the baseline with a value of 85.8% compared to 73.1%, also outperforming models based solely on RCI and median Raman spectra. Feature fusion of DP and RCI does not improve the more trivial task of tumour identification but does deliver an observed advantage in G3/G4 discrimination. Building on these promising findings, future work could include the acquisition of larger datasets for enhanced model generalization