Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and β\u3csub\u3e2\u3c/sub\u3e-agonist use

Background Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this brake on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo β2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. Methods Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for β2-adrenergic receptor haplotype determination. Results Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the β2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. Conclusion Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to β-agonist. The decreased phosphorylation does not appear to be associated with a particular β2-adrenergic receptor haplotype. The observed decrease in VASP phosphorylation suggests greater inhibition of actin reorganization which is necessary for altering attachment and migration required during epithelial repair

Ceramic Rail-Race Ball Bearings

Non-lubricated ball bearings featuring rail races have been proposed for use in mechanisms that are required to function in the presence of mineral dust particles in very low-pressure, dry environments with extended life. Like a conventional ball bearing, the proposed bearing would include an inner and an outer ring separated by balls in rolling contact with the races. However, unlike a conventional ball bearing, the balls would not roll in semi-circular or gothic arch race grooves in the rings: instead, the races would be shaped to form two or more rails (see figure). During operation, the motion of the balls would push dust particles into the spaces between the rails where the particles could not generate rolling resistance for the ball

Environmental assessment of Swedish clothing consumption - six garments, sustainable futures

The aim of this work was to map and understand the current environmental impact of Swedish clothing consumption. A life cycle assessment (LCA) was used to evaluate the environmental impact of six garments: a T-shirt, a pair of jeans, a dress, a jacket, a pair of socks, and a hospital uniform, using indicators of climate impact (also called “carbon footprint”), energy use, water scarcity, land use impact on soil quality, freshwater ecotoxicity, and human toxicity. The environmental impact of the six garments was then scaled up to represent Swedish national clothing consumption over one year.In addition to fulfilling this aim, the report is a unique and rich source of transparently documented inventory data on a large number of textile processes – hopefully this can be of use for other LCA practitioners. The report updates Roos et al. (2015), which was the first detailed LCA study of Swedish clothing consumption at the national level. Since the publication of the first edition, several LCA studies of textile production processes and global apparel consumption have been published, which have enabled us to refine the inventory model and benchmark the results.The work was done in Mistra Future Fashion, a cross-disciplinary research program in 2011-2019 which aimed to enable a systemic change in the Swedish fashion industry leading to sustainable development in industry and society

Saddle pulmonary embolism diagnosed by CT angiography: Frequency, clinical features and outcome

SummaryObjectiveTo assess the frequency, clinical presentation and outcome associated with saddle pulmonary embolism (PE) diagnosed by computed tomographic angiography (CTA).PatientsRetrospective review of 546 consecutive patients diagnosed to have acute PE by CTA from 1 September 2002 to 31 December 2003.ResultsFourteen of 546 patients (2.6%) had saddle PE; 10 were men (71%). None of these patients had pre-existing cardiopulmonary disease. Most common presenting symptoms included dyspnea (72%) and syncope (43%). Hypotension was documented in 2 patients (14%). The most common risk factor for PE was obesity (64%). CTA revealed saddle PE and additional filling defects in the main pulmonary arteries in all patients. Echocardiography was performed within 48h of the PE diagnosis in 10 patients and revealed right ventricular dysfunction in 8 (80%). All patients were initially managed in the hospital, median length of stay of 4 days (range, 1–45 days). Standard anticoagulant therapy with heparin and warfarin was administered to all patients. Five patients (36%) received additional therapy; thrombolytic therapy was administered to 1 patient (7%) and 4 patients (29%) received an inferior vena cava filter. None of the patients died during their hospitalization. Four patients (29%) died following their hospitalization after intervals of 1, 5, 6, and 12 months, respectively. Causes of death were known in 3 patients, all of whom died from progressive malignancy.ConclusionSaddle PE in patients without pre-existing cardiopulmonary disease is associated with a relatively low in-hospital mortality rate and may not necessitate aggressive medical management

Examination of Different Accelerometer Cut-Points for Assessing Sedentary Behaviors in Children

Background: Public health research on sedentary behavior (SB) in youth has heavily relied on accelerometers. However, ithas been limited by the lack of consensus on the most accurate accelerometer cut-points as well as by unknown effectscaused by accelerometer position (wrist vs. hip) and output (single axis vs. multiple axes). The present study systematicallyevaluates classification accuracy of different Actigraph cut-points for classifying SB using hip and wrist-worn monitors andestablishes new cut-points to enable use of the 3-dimensional vector magnitude data (for both hip and wrist placement).Methods: A total of 125 children ages 7–13 yrs performed 12 randomly selected activities (from a set of 24 differentactivities) for 5 min each while wearing tri-axial Actigraph accelerometers on both the hip and wrist. The accelerometer datawere categorized as either sedentary or non-sedentary minutes using six previously studied cut-points: 100counts-per-minute (CPM), 200CPM, 300CPM, 500CPM, 800CPM and 1100CPM. Classification accuracy was evaluated with Cohen’s Kappa(k) and new cut-points were identified from Receiver Operating Characteristic (ROC).Results: Of the six cut-points, the 100CPM value yielded the highest classification accuracy (k = 0.81) for hip placement. Forwrist placement, all of the cut-points produced low classification accuracy (ranges of k from 0.44 to 0.67). Optimal sedentarycut-points derived from ROC were 554.3CPM (ROC-AUC of 0.99) for vector magnitude for hip, 1756CPM (ROC-AUC of 0.94)for vertical axis for wrist, and 3958.3CPM (ROC-AUC of 0.93) for vector magnitude for wrist placement.Conclusions: The 100CPM was supported for use with vertical axis for hip placement, but not for wrist placement. The ROC-derived cut-points can be used to classify youth SB with the wrist and with vector magnitude data

Consequences of activating the calcium-permeable ion channel TRPV1 in breast cancer cells with regulated TRPV1 expression

Increased expression of specific calcium channels in some cancers and the role of calcium signaling in proliferation and invasion have led to studies assessing calcium channel inhibitors as potential therapies for some cancers. The use of channel activators to promote death of cancer cells has been suggested, but the risk of activators promoting cancer cell proliferation and the importance of the degree of channel over-expression is unclear. We developed an MCF-7 breast cancer cell line with inducible TRPV1 overexpression and assessed the role of TRPV1 levels on cell death mediated by the TRPV1 activator capsaicin and the potential for submaximal activation to promote proliferation. The TRPV1 level was a determinant of cell death induced by capsaicin. A concentration response curve with varying TRPV1 expression levels identified the minimum level of TRPV1 required for capsaicin induced cell death. At no level of TRPV1 over-expression or capsaicin concentration did TRPV1 activation enhance proliferation. Cell death induced by capsaicin was necrotic and associated with up-regulation of c-Fos and RIP3. These studies suggest that activators of specific calcium channels may be an effective way to induce necrosis and that this approach may not always be associated with enhancement of cancer cell proliferation

LCA on fast and slow garment prototypes

This report summarises the environmental assessment work done in the Mistra Future\ua0Fashion program focussed on the potential to improve the environmental performance\ua0of garments and adapt them to a circular economy. The approaches examined in this\ua0report include reducing the environmental impacts from fast-fashion trends by making\ua0garments from paper-based materials, or by extending garment life cycles.This assessment considers two paper-based garments. One is made primarily from paper pulp but enhanced with a polylactic acid polymer. This garment is worn between\ua0two to five times before being recycled as newspaper. The other fast garment is\ua0made of paper pulp, polylactic acid and nanocellulose. It has a similar life cycle but\ua0is composted after use life. These garments are compared with a standard t-shirt. The report also considers a slow-paced scenario in which a polyester garment passes between several owners and is regularly changed to maintain its appeal. It is updated\ua0with a transfer sublimation overprint three times, making the garment darker each\ua0time. Later it is joined with an outer shell of new material using laser technology tomake a cropped, box-cut jacket.The assessment was performed using environmental life cycle assessment. More\ua0particularly, the assessment was based on attributional process analysis with cutoff allocation procedures and comparison with a traditional reference garment life cycle. Key environmental effect categories considered here include climate change (greenhouse gas emissions), freshwater eutrophication, freshwater ecotoxicity and human toxicity (cancer and non-cancer).The results indicate that the environmental outcomes of the paper-based garments can be competitive with the reference garment, particularly when the user is assumed to throw away a fully functional reference garment after five uses. This assumption may be true for some users, but the number of uses is considerably lower than the typical or the potential lifespan of the reference garment. The main factor assisting the paper-based garments is the reduction in the impacts per mass associated with material manufacturing (fibres, spinning, knitting), and also their lighter masses.\ua0Avoided impacts in the use phase play a secondary role on account of their location in\ua0Sweden with its low-carbon energy mix. The long-life garments are also competitivecompared with their reference garments. This is primarily a consequence of how extending garment life avoids the production of new garments. The environmental impacts associated with transfer sublimation dye reprinting and laser processing do\ua0not significantly impact the overall environmental performance of the extended longlife\ua0garments, though confidentiality of data prevents a full assessment of these.The garments in this report are pilot products and explorative scenarios rather\ua0than attempts to model existing business or behavioural patterns. The reader\ua0should therefore take care to keep the results in context when interpreting them.\ua0Nevertheless, the results suggest the value of pursuing the potential associated with these garment life cycles. We should also bear in mind that while the reference garments in this assessment are based on typical usage patterns, other more\ua0sustainable patterns are feasible

Superovulation with human chorionic gonadotropin (hCG) trigger and gonadotropin releasing hormone agonist (GnRHa) trigger differentially alter essential angiogenic factors in the endometrium in a mouse ART model†.

Gonadotropin-releasing hormone agonists (GnRHa) are used as an alternative to human chorionic gonadotropin (hCG) to trigger ovulation and decrease the risk of ovarian hyperstimulation syndrome. GnRHa is less potent at inducing ovarian vascular endothelial growth factor (VEGF), but may also affect endometrial angiogenesis and early placental development. In this study, we explore the effect of superovulation on endometrial angiogenesis during critical periods of gestation in a mouse model. We assigned female mice to three groups: natural mating or mating following injection with equine chorionic gonadotropin and trigger with GnRHa or hCG trigger. Females were killed prior to implantation (E3.5), post-implantation (E7.5), and at midgestation (E10.5), and maternal serum, uterus, and ovaries were collected. During peri-implantation, endometrial Vegfr1 and Vegfr2 mRNA were significantly increased in the GnRHa trigger group (P < 0.02) relative to the hCG group. Vegfr1 is highly expressed in the endometrial lining and secretory glands immediately prior to implantation. At E7.5, the ectoplacental cone expression of Vegfa and its receptor, Vegfr2, was significantly higher in the hCG trigger group compared to the GnRHa group (P < 0.05). Soluble VEGFR1 and free VEGFA were much higher in the serum of mice exposed to the hCG trigger compared to GnRHa group. At midgestation, there was significantly more local Vegfa expression in the placenta of mice triggered with hCG. GnRHa and hCG triggers differentially disrupt the endometrial expression of key angiogenic factors during critical periods of mouse gestation. These results may have significant implications for placental development and neonatal outcomes following human in vitro fertilization

New Five Dimensional Black Holes Classified by Horizon Geometry, and a Bianchi VI Braneworld

We introduce two new families of solutions to the vacuum Einstein equations with negative cosmological constant in 5 dimensions. These solutions are static black holes whose horizons are modelled on the 3-geometries nilgeometry and solvegeometry. Thus the horizons (and the exterior spacetimes) can be foliated by compact 3-manifolds that are neither spherical, toroidal, hyperbolic, nor product manifolds, and therefore are of a topological type not previously encountered in black hole solutions. As an application, we use the solvegeometry solutions to construct Bianchi VI$_{-1}$ braneworld cosmologies.Comment: LaTeX, 20 pages, 2 figures Typographical errors corrected, and references to printed matter added in favour of preprints where possibl

An automated epifluorescence microscopy imaging assay for the identification of phospho-AKT level modulators in breast cancer cells

AKT is an enzyme of the PI3K/pAKT pathway, regulating proliferation and cell survival. High basal levels of active, phosphorylated AKT (pAKT) are associated with tumor progression and therapeutic resistance in some breast cancer subtypes, including HER2 positive breast cancers. Various stimuli can increase pAKT levels and elevated basal pAKT levels are a feature of PTEN-deficient breast cancer cell lines. The aim of this study was to develop an assay able to identify modulators of pAKT levels using an automated epifluorescence microscope and high content analysis. To develop this assay, we used HCC-1569, a PTEN-deficient, HER2-overexpressing breast cancer cell line with elevated basal pAKT levels. HCC-1569 cells were treated with a selective pharmacological inhibitor of AKT (MK-2206) to reduce basal pAKT levels or EGF to increase pAKT levels. Immunofluorescence images were acquired using an automated epifluorescence microscope and integrated intensity of cytoplasmic pAKT staining was calculated using high content analysis software. Mean and median integrated cytoplasmic intensity were normalized using fold change and standard score to assess assay quality and to identify most robust data analysis. The highest z' factor was achieved for median data normalization using the standard score method (z' = 0.45). Using our developed assay we identified the calcium homeostasis regulating proteins TPRV6, STIM1 and TRPC1 as modulators of pAKT levels in HCC-1569 cells. Calcium signaling controls a diverse array of cellular processes and some calcium homeostasis regulating proteins are involved in modulating pAKT levels in cancer cells. Thus, these identified hits present promising targets for further assessment