Warming the Whare for trans people and whānau in perinatal care

Final deliverable report for the project: Understanding the need for trans, non-binary and takatāpui inclusive perinatal care (HRC 20/1498

Guide to Implementing DevSecOps for a System of Systems in Highly Regulated Environments

DevSecOps (DSO) is an approach that integrates development (Dev), security (Sec), and delivery/operations (Ops) of software systems to reduce the time from need to capability and provide continuous integration and continuous delivery (CI/CD) with high software quality. The rapid acceptance and demonstrated effectiveness of DSO in software system development have led to proposals for its adoption in more complex projects. This document provides guidance to projects interested in implementing DSO in defense or other highly regulated environments, including those involving systems of systems.The report provides rationale for adopting DSO and the dimensions of change required for that adoption. It introduces DSO, its principles, operations, and expected benefits. It describes objectives and activities needed to implement the DSO ecosystem, including preparation, establishment, and management. Preparation is necessary to create achievable goals and expectations and to establish feasible increments for building the ecosystem. Establishing the ecosystem includes evolving the culture, automation, processes, and system architecture from their initial state toward an initial capability. Managing the ecosystem includes measuring and monitoring both the health of the ecosystem and the performance of the organization. Additional information on the conceptual foundations of the DSO approach is also provided. </p

Mast Cell Tryptase Release Contributes to Disease Progression in Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis is a multisystem disease causing lung cysts and respiratory failure. Loss of tuberous sclerosis complex (TSC) gene function results in a clone of 'LAM cells' with dysregulated mTOR activity. LAM cells and fibroblasts form lung nodules that also contain mast cells although their significance is unknown. To understand the mechanism of mast cell accumulation and their role in the pathogenesis of LAM. Methods, Measurements and Main Results: Transcriptional profiling, quantitative RT-PCR and ELISA showed that LAM derived cell / fibroblast co-cultures induced multiple CXC chemokines in fibroblasts. Compared with normal tissue, LAM lungs had increased tryptase positive mast cells expressing CXC chemokine receptors (p<0.05). Mast cells located around the periphery of LAM nodules were positively associated with rate of lung function loss (p=0.016). In vitro, LAM spheroid TSC2 null cell / fibroblast co-cultures attracted mast cells, which was inhibited by pharmacologic and CRISPR-cas9 inhibition of CXCR1 and 2. LAM spheroids caused mast cell tryptase release, which induced fibroblast proliferation and increased LAM spheroid size (1.36±0.24 fold, p=0.0019). The tryptase inhibitor APC366 and sodium cromoglycate inhibited mast cell induced spheroid growth. Using an immuno-competent Tsc2 null murine homograft model, sodium cromoglycate markedly reduced mast cell activation and Tsc2 null lung tumour burden (vehicle: 32.5.3%±23.6 and cromoglycate: 5.5%±4.3. p=0.0035). LAM cell / fibroblast interactions attract mast cells where tryptase release contributes to disease progression. Repurposing sodium cromoglycate for use in LAM should be studied as an alternative or adjunct to mTOR inhibitor therapy

Electroplate and Lift Lithography for Patterned Micro/Nanowires Using Ultrananocrystalline Diamond (UNCD) as a Reusable Template

A fast, simple, scalable technique is described for the controlled, solution-based, electrochemical synthesis of patterned metallic and semiconducting nanowires from reusable, nonsacrificial, ultrananocrystalline diamond (UNCD) templates. This enables the repeated fabrication of arrays of complex patterns of nanowires, potentially made of any electrochemically depositable material. Unlike all other methods of patterning nanowires, this benchtop technique quickly mass-produces patterned nanowires whose diameters are not predefined by the template, without requiring intervening vacuum or clean room processing. This technique opens a pathway for studying nanoscale phenomena with minimal equipment, allowing the process-scale development of a new generation of nanowire-based devices

Electroplate and Lift Lithography for Patterned Micro/Nanowires Using Ultrananocrystalline Diamond (UNCD) as a Reusable Template

A fast, simple, scalable technique is described for the controlled, solution-based, electrochemical synthesis of patterned metallic and semiconducting nanowires from reusable, nonsacrificial, ultrananocrystalline diamond (UNCD) templates. This enables the repeated fabrication of arrays of complex patterns of nanowires, potentially made of any electrochemically depositable material. Unlike all other methods of patterning nanowires, this benchtop technique quickly mass-produces patterned nanowires whose diameters are not predefined by the template, without requiring intervening vacuum or clean room processing. This technique opens a pathway for studying nanoscale phenomena with minimal equipment, allowing the process-scale development of a new generation of nanowire-based devices

<i>GSTCD</i> and <i>INTS12</i> gene expression is altered following exposure of HASM cells to TGFβ1.

<p>Human airway smooth muscle (HASM) cells were exposed to 10ng/ml TGFβ1 for 4 or 24 hours. Open bars depict <i>GSTCD</i> expression whereas black bars show <i>INTS12</i> expression. Values shown are mean and standard error of the mean (SEM) (n=5). Significant increases in both <i>GSTCD</i> and <i>INTS12</i> gene expression were observed following 24h exposure to TGFβ1 (<i>P</i><0.05 <i>GSTCD</i>, <i>P</i><0.01 <i>INTS12</i>) and after 4h TGFβ1 exposure in <i>INTS12</i> expression (<i>P</i><0.05).</p

Correlation of <i>GSTCD</i> (A) and <i>INTS12</i> (B) lung mRNA levels with percent predicted FEV₁ in the lungs of 848 individuals (see Table S5 for patient demographics).

<p>Correlation of <i>GSTCD</i> (A) and <i>INTS12</i> (B) lung mRNA levels with percent predicted FEV₁ in the lungs of 848 individuals (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074630#pone.0074630.s009" target="_blank">Table S5</a> for patient demographics).</p

Genetic architecture of the region containing both <i>GSTCD</i> and <i>INTS12</i> genes.

<p>The top panel depicts gene arrangements previously reported in NCBI, build 37, whereas the lower panel shows novel variants identified in lung. V1, 2, 3 refer to splice variants 1, 2 and 3 for each gene. Open boxes represent exons and connecting black lines represent introns. Also illustrated are the locations of Single Nucleotide Polymorphisms (SNPs) meeting genome-wide association (<i>P</i>≤5x10^-8) for FEV₁ in previously reported analyses of the SpiroMeta consortium [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074630#B5" target="_blank">5</a>]. Highlighted in red is the sentinel SNP rs10516526 that was associated with FEV₁ (<i>P</i>=2.18 x 10^-23 in all stage analyses) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074630#B5" target="_blank">5</a>]. Translation start codons (ATG) are shown boxed in green and stop codons (TAA) boxed in red.</p

A: Expression of <i>GSTCD</i> and <i>INTS12</i> mRNA in Lung and Airway cells.

<p>mRNA expression in human airway smooth muscle (HASM) cells, human bronchial epithelial cells (HBEC) and peripheral blood mononuclear cells (PBMC) is shown relative to mRNA from lung. Open bars depict <i>GSTCD</i> expression whereas black bars show <i>INTS12</i> expression. Values shown are mean and standard error of the mean (SEM) (n=3). Only the expression of <i>GSTCD</i> in HBEC relative to lung was statistically significant (* <i>P</i>=0.0494). <b>B</b>: <b>Correlation between <i>GSTCD</i> and <i>INTS12</i> ΔCt values in HASM, HBEC, PBMC and lung</b>. mRNA expression levels as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074630#pone-0074630-g003" target="_blank">Figure 3A</a> from human airway smooth muscle (HASM) cells, human bronchial epithelial cells (HBEC), peripheral blood mononuclear cells (PBMC) and lung were correlated using a scatter plot. The correlation coefficient between these measures was r=0.8, <i>P</i><0.0001. <b>C</b>: <b>Correlation between <i>GSTCD</i> and <i>INTS12</i> mRNA levels in the lung</b>. The scatter plot shows a positive correlation between the <i>GSTCD</i> and <i>INTS12</i> probe sets as investigated in the lung eQTL study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074630#B20" target="_blank">20</a>].</p

Regulatory motifs within the <i>GSTCD/INTS12</i> locus.

<p>The <i>GSTCD</i>/<i>INTS12</i> locus is shown, annotated with RNA sequencing, H3K27Ac histone marks, DNase hypersensitivity, transcription factor binding and CpG islands (UCSC Genome Browser (<a href="http://genome.ucsc.edu/" target="_blank"><u>http://genome.ucsc.edu/</u></a>)) on the Human Feb 2009 (GRCh37/hg19) assembly. For the H3K27Ac histone marks and RNA sequence tracks, peak height is proportional to signal amplitude, with colours representing datasets in different cell backgrounds (pale blue H3K27Ac histone trace = human umbilical vein endothelial cell (HUVEC); blue/grey = K562 erythroleukaemia cells). For the DNase hypersensitivity and transcription factor binding tracks, a grey band indicates the extent of the hypersensitive region and the intensity of the band is proportional to the maximum signal strength observed in any cell line.</p