A method for controlling parachute deployment conditions in simulated planetary environments

Controlling parachute deployment conditions in simulated planetary environment

The humane containment of mentally disordered prisoners .

In many western countries, including New Zealand (NZ), the humane containment of mentally disordered prisoners (MOP) has became a topical issue in recent years. The current review of the literature demonstrated that there is little agreement regarding what measures are required to effectively address this somewhat complex matter and that there is a dearth of empirical research in this area, especially in NZ. The purpose of the current research was to empirically investigate this issue, within the framework of prisoners' rights in NZ, to ascertain whether there is an inherent gap between MOP's legal entitlements to mental health treatment (MHT) and the practical fulfilment of these rights. First, this was quantified by establishing an estimated base rate of clinically diagnosed MOP, and then by statistically verifying such persons’ access to MHT via an in-depth analysis of both the detection and referral process and the treatment delivery system currently in operation to service the mental health needs of prisoners at a local medium security men's prison in NZ. A randomised sample of one hundred medium security male inmates was obtained to ascertain a base rate of clinically MOP. Interviews were conducted, using the structured clinical interview for the OSM-111-R (SCIO). The results showed that 62.8% of the final sample (n=94) had a clinically diagnosed disorder and that co­ occurring disorders, especially substance use comorbidity, were prevailing issues. Analysis of the detection procedure involved a three-tiered examination; perusing the accuracy rate of detection, establishing what variables influenced a referral, and comparing these components with the referral process for rehabilitative MHT. The detection accuracy of participants with a substance use disorder was found to be significant, however, the detection rates of MOP and of participants requiring rehabilitative MHT for sexual or violent offence related issues were not found to function beyond the level of chance. Multivariate analysis revealed that visible signs of psychopathology, mental health history and atypical criminal characteristics increased the likelihood of detection. However, the majority of the MOP in this study were not detected. The examination of the treatment delivery system comprised a similar three-tiered analysis. The treatment delivery rate for MOP was not found to be statistical significant and neither was the overall delivery of rehabilitative MHT. Factors involved in treatment delivery were also explored and the findings collectively showed that the delivery of MHT for MOP primarily functioned as crisis intervention rather than humane containment. The practical implications of these research findings are discussed in relation to MOP's moral and legal entitlements to MHT and recommendations are made

Determination of the total grain size distribution in a Vulcanian eruption column, and its implications to stratospheric aerosol perturbation

Grain size analysis of samples representing all sampleable portions of the airfall deposit produced by the Fuego volcano in Guatemala on 14 October 1974 form the basis for estimating the total grain size distribution of tephra from this eruption. The region enclosed by each isopach has a particular average grain size distribution which can be weighted proportionally to its percentage volume. The grain size of pyroclastic avalanche deposits produced during the eruption are also included. The total grain size distribution calculated as a sum of weighted distributions has a median grain size of 0.8∅ (0.6mm) and a sorting coefficient (σ∅) of 2.3. The size distribution seems to approximate Rosin and Rammler\u27s law of crushing and this observation allows us to estimate that no more than 15% volume of the fine tail of the total size distribution is likely to be missing. The ash composed of these fine particles did not fall in the region of the volcano as part of the recognizable tephra blanket. The eruption column reached well into the stratosphere: heights estimated from the ground were 10-12 km above sea level but estimated heights based on mass flux rates are higher (18-23 km). The proportion of ash smaller than 2 µm, which could remain for substantial periods in the stratosphere, is no more than 0.8% volume of the total. It seems probable that acid aerosol particles from vulcanian type eruptions are more important to stratospheric aerosol perturbation than fine silicate ash particles by at least an order of magnitude

CARBON ADSORBER FIRE EXTINGUISHMENT TESTS.

This report describes protecting the Aviated carbon adsorbers from fire

Changes in epithelial proportions and transcriptional state underlie major premenopausal breast cancer risks

The human breast undergoes lifelong remodeling in response to estrogen and progesterone, but hormone exposure also increases breast cancer risk. Here, we use single-cell analysis to identify distinct mechanisms through which breast composition and cell state affect hormone signaling. We show that prior pregnancy reduces the transcriptional response of hormone-responsive (HR+) epithelial cells, whereas high body mass index (BMI) reduces overall HR+ cell proportions. These distinct changes both impact neighboring cells by effectively reducing the magnitude of paracrine signals originating from HR+ cells. Because pregnancy and high BMI are known to protect against hormone-dependent breast cancer in premenopausal women, our findings directly link breast cancer risk with person-to-person heterogeneity in hormone responsiveness. More broadly, our findings illustrate how cell proportions and cell state can collectively impact cell communities through the action of cell-to-cell signaling networks

Effect of mineralocorticoid receptor antagonists on cardiac function in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials

Heart failure with preserved ejection fraction (HFpEF) is a disease with limited evidence-based treatment options. Mineralocorticoid receptor antagonists (MRA) offer benefit in heart failure with reduced ejection fraction (HFrEF), but their impact in HFpEF remains unclear. We therefore evaluated the effect of MRA on echocardiographic, functional, and systemic parameters in patients with HFpEF by a systematic review and meta-analysis. We searched MEDLINE, EMBASE, clinicaltrials.gov, and Cochrane Clinical Trial Collection to identify randomized controlled trials that (a) compared MRA versus placebo/control in patients with HFpEF and (b) reported echocardiographic, functional, and/or systemic parameters relevant to HFpEF. Studies were excluded if: they enrolled asymptomatic patients; patients with HFrEF; patients after an acute coronary event; compared MRA to another active comparator; or reported a follow-up of less than 6 months. Primary outcomes were changes in echocardiographic parameters. Secondary end-points were changes in functional capacity, quality of life measures, and systemic parameters. Quantitative analysis was performed by generating forest plots and calculating effect sizes by random-effect models. Between-study heterogeneity was assessed through Q and I2 statistics. Nine trials with 1164 patients were included. MRA significantly decreased E/e′ (mean difference − 1.37, 95% confidence interval − 1.72 to − 1.02), E/A (− 0.04, − 0.08 to 0.00), left ventricular end-diastolic diameter (− 0.78 mm, − 1.34 to − 0.22), left atrial volume index (− 1.12 ml/m2, − 1.91 to − 0.33), 6-min walk test distance (− 11.56 m, − 21 to − 2.13), systolic (− 4.75 mmHg, − 8.94 to − 0.56) and diastolic blood pressure (− 2.91 mmHg, − 4.15 to − 1.67), and increased levels of serum potassium (0.23 mmol/L, 0.19 to 0.28) when compared with placebo/control. In patients with HFpEF, MRA treatment significantly improves indices of cardiac structure and function, suggesting a decrease in left ventricular filling pressure and reverse cardiac remodeling. MRA increase serum potassium and decrease blood pressure; however, a small decrease in 6-min-walk distance is also noted. Larger prospective studies are warranted to provide definitive answers on the effect of MRA in patients with HFpEF

Changes in epithelial proportions and transcriptional state underlie major premenopausal breast cancer risks

The human breast undergoes lifelong remodeling in response to estrogen and progesterone, but hormone exposure also increases breast cancer risk. Here, we use single-cell analysis to identify distinct mechanisms through which breast composition and cell state affect hormone signaling. We show that prior pregnancy reduces the transcriptional response of hormone-responsive (HR+) epithelial cells, whereas high body mass index (BMI) reduces overall HR+ cell proportions. These distinct changes both impact neighboring cells by effectively reducing the magnitude of paracrine signals originating from HR+ cells. Because pregnancy and high BMI are known to protect against hormone-dependent breast cancer in premenopausal women, our findings directly link breast cancer risk with person-to-person heterogeneity in hormone responsiveness. More broadly, our findings illustrate how cell proportions and cell state can collectively impact cell communities through the action of cell-to-cell signaling networks

Proteomic Analysis of GLUT4 Storage Vesicles Reveals Tumor Suppressor Candidate 5 (TUSC5) as a Novel Regulator of Insulin Action in Adipocytes.

Insulin signaling augments glucose transport by regulating glucose transporter 4 (GLUT4) trafficking from specialized intracellular compartments, termed GLUT4 storage vesicles (GSVs), to the plasma membrane. Proteomic analysis of GSVs by mass spectrometry revealed enrichment of 59 proteins in these vesicles. We measured reduced abundance of 23 of these proteins following insulin stimulation and assigned these as high confidence GSV proteins. These included established GSV proteins such as GLUT4 and insulin-responsive aminopeptidase, as well as six proteins not previously reported to be localized to GSVs. Tumor suppressor candidate 5 (TUSC5) was shown to be a novel GSV protein that underwent a 3.7-fold increase in abundance at the plasma membrane in response to insulin. siRNA-mediated knockdown of TUSC5 decreased insulin-stimulated glucose uptake, although overexpression of TUSC5 had the opposite effect, implicating TUSC5 as a positive regulator of insulin-stimulated glucose transport in adipocytes. Incubation of adipocytes with TNFα caused insulin resistance and a concomitant reduction in TUSC5. Consistent with previous studies, peroxisome proliferator-activated receptor (PPAR) γ agonism reversed TNFα-induced insulin resistance. TUSC5 expression was necessary but insufficient for PPARγ-mediated reversal of insulin resistance. These findings functionally link TUSC5 to GLUT4 trafficking, insulin action, insulin resistance, and PPARγ action in the adipocyte. Further studies are required to establish the exact role of TUSC5 in adipocytes

Opportunities for organoids as new models of aging.

The biology of aging is challenging to study, particularly in humans. As a result, model organisms are used to approximate the physiological context of aging in humans. However, the best model organisms remain expensive and time-consuming to use. More importantly, they may not reflect directly on the process of aging in people. Human cell culture provides an alternative, but many functional signs of aging occur at the level of tissues rather than cells and are therefore not readily apparent in traditional cell culture models. Organoids have the potential to effectively balance between the strengths and weaknesses of traditional models of aging. They have sufficient complexity to capture relevant signs of aging at the molecular, cellular, and tissue levels, while presenting an experimentally tractable alternative to animal studies. Organoid systems have been developed to model many human tissues and diseases. Here we provide a perspective on the potential for organoids to serve as models for aging and describe how current organoid techniques could be applied to aging research

Comparative oncogenomics identifies breast tumors enriched in functional tumor-initiating cells

The claudin-low subtype is a recently identified rare molecular subtype of human breast cancer that expresses low levels of tight and adherens junction genes and shows high expression of epithelial-to-mesenchymal transition (EMT) genes. These tumors are enriched in gene expression signatures derived from human tumor-initiating cells (TICs) and human mammary stem cells. Through cross-species analysis, we discovered mouse mammary tumors that have similar gene expression characteristics as human claudin-low tumors and were also enriched for the human TIC signature. Such claudin-low tumors were similarly rare but came from a number of distinct mouse models, including the p53 null transplant model. Here we present a molecular characterization of 50 p53 null mammary tumors compared with other mouse models and human breast tumor subtypes. Similar to human tumors, the murine p53 null tumors fell into multiple molecular subtypes, including two basal-like, a luminal, a claudin-low, and a subtype unique to this model. The claudin-low tumors also showed high gene expression of EMT inducers, low expression of the miR-200 family, and low to absent expression of both claudin 3 and E-cadherin. These murine subtypes also contained distinct genomic DNA copy number changes, some of which are similarly altered in their cognate human subtype counterpart. Finally, limiting dilution transplantation revealed that p53 null claudin-low tumors are highly enriched for TICs compared with the more common adenocarcinomas arising in the same model, thus providing a unique preclinical mouse model to investigate the therapeutic response of TICs