Hermes CX-7: Air transport system design simulation

The Hermes CX-7 has been designed to service the overnight parcel package delivery needs of the cities of Aeroworld as determined in the G-Dome Enterprises market survey. The design optimization centers on the prime goal of servicing the needs of these cities as efficiently and profitably as possible. The greatest factors which affect the design of an aircraft for the mission outlined in the Request for Proposal are cost, construction feasibility and effectiveness of the design. Other influencing factors are given by the constraints of the market, including a maximum takeoff and landing distance of 60 feet, storage capability in a container of size 5 ft. x 3 ft. x 2 ft., cargo packages of 2 inch and 4 inch cubes, and ability to turn with a radius no larger than 60 feet. Safety considerations such as flying at or below Mach one (30 ft/s) and controllability and maintainability of the aircraft must also be designed into the aircraft. Another influential factor is the efficiency of the aircraft which involves optimizations and tradeoffs of such factors as weight, lifting surface sizing, structural redundancy, and material costs

Degrees of Freedom: Designing Information and Communication Technologies to Support Enhanced Agency for Blind and Partially Sighted Individuals Through Cross-Sensory Information Representation

A significant change in working and learning environments has taken place in recent years, since the beginning of the COVID-19 pandemic. The core of this shift is a steadily greater reliance on information and communication technologies (ICTs) to mediate representations of information. For blind and partially sighted individuals (BPSIs), this has been a difficult transition that has carried many inclusive and accessible design challenges along with it. This study is concerned with the limitations and compromises on BPSIs’ agency when relying on ICTs for equitable access to information relative to their sighted peers, and how designers of ICTs could responsibly use design recommendations aimed at supporting equal agency for these users. Actively shaping ICTs to be highly cross-sensory, interactive and navigable without a reliance on vision would be a step towards equal agency for BPSIs and making ICTs more inclusive. A research process was conducted comprised of functional usability testing of conventional ICT platforms (i.e. Zoom, Microsoft Teams and Google Meets), semi-structured interviews focused on narrative exploration of BPSIs’ lived experiences with ICT use in working and learning environments, and longitudinal co-design workshops aimed at collaboratively building, testing and iterating on low-fidelity prototype ICTs. Through these activities, a suite of relevant themes were found, including the effectiveness of interactive information foraging, filtering for relevance, using different granularities of information depending on context, and navigation of the diagrammatic representations of ICTs using sensory-grounded language. Preliminary design recommendations for inclusive design of ICTs were informed by these outcomes, such as ensuring large quantities of information are curated interactively, providing appropriate choice selection relative to relevance to users’ goals and intentions, and holding organizations accountable for representation of BPSIs in decisions relating to ICT service provision. These outcomes suggest a promising future area of design research may have been articulated via these concerns for accessibility, management, navigation, and sensory-grounded representation of information

Control and reduction of unsteady pressure loads in separated shock wave turbulent boundary layer interaction

The focus was on developing means of controlling and reducing unsteady pressure loads in separated shock wave turbulent boundary layer interactions. Section 1 describes how vortex generators can be used to effectively reduce loads in compression ramp interaction, while Section 2 focuses on the effects of 'boundary-layer separators' on the same interaction

Trajectories of Exposure to Neighborhood Deprivation and the Odds of Experiencing Intimate Partner Violence Among Women: Are There Sensitive Periods for Exposure?

Neighborhood disadvantage is commonly hypothesized to be positively associated with intimate partner violence (IPV) against women. However, longitudinal investigation of this association has been limited, with no studies on whether the timing of exposure matters. We used data from 2,115 women in the UK-based Avon Longitudinal Study of Parents and Children. Exposure to neighborhood-level deprivation was measured at 10-time points from baseline (gestation) until age 18. Family-level socioeconomic characteristics were measured at baseline. At age 21, participants self-reported whether they had experienced any IPV since age 18. We used a three-step bias-adjusted longitudinal latent class analysis to investigate how different patterns of neighborhood deprivation exposure were associated with the odds of experiencing IPV. A total of 32% of women experienced any IPV between ages 18 and 21. Women who consistently lived in deprived neighborhoods (chronic high deprivation) or spent their early childhoods in more deprived neighborhoods and later moved to less deprived neighborhoods (decreasing deprivation) had higher odds of experiencing IPV compared to those who consistently lived in non-deprived neighborhoods. The odds of experiencing IPV did not consistently differ between women who lived in non-deprived neighborhoods during early childhood and later moved to deprived neighborhoods (increasing deprivation) and those stably in non-deprived neighborhoods. Living in more deprived neighborhoods during early childhood, regardless of later exposure, was associated with higher odds of experiencing later IPV. This is congruent with prior research demonstrating the persistent effects of early neighborhood disadvantage on health and well-being. Replication, and underlying mechanisms, should be assessed across contexts

Visit-to-visit variability of lipid measurements as predictors of cardiovascular events.

BACKGROUND:Higher visit-to-visit variability in risk factors such as blood pressure and low-density lipoprotein (LDL)-cholesterol are associated with an increase in cardiovascular (CV) events. OBJECTIVE:The purpose of this study was to determine whether variability in high-density lipoprotein cholesterol (HDL-C) and triglyceride levels predicted coronary and CV events in a clinical trial population with known coronary disease. METHODS:We assessed intraindividual variability in fasting high-density lipoprotein (HDL)-cholesterol, triglyceride, and LDL-cholesterol measurements among 9572 patients in the Treating to New Targets trial and correlated the results with coronary events over a median follow-up of 4.9 years. RESULTS:In the fully adjusted Cox model, 1 standard deviation of average successive variability, defined as the average absolute difference between successive values, was associated with an increased risk of a coronary event for HDL-cholesterol (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.11-1.21, P < .0001), for triglycerides (HR 1.09, 95% CI 1.04-1.15, P = .0005), and for LDL-cholesterol (HR 1.14, 95% CI 1.09-1.19, P < .0001). Similar results were found for the 3 other measures of variability, standard deviation, coefficient of variability, and variability independent of the mean. Similar results were seen for CV events, stroke, and nonfatal myocardial infarction. Higher variability in triglyceride and LDL-cholesterol, but not HDL-cholesterol, was predictive of incident diabetes. The correlation among the variability of the 3 lipid measurements was weak. CONCLUSION:Visit-to-visit variability in fasting measurements of HDL-cholesterol, triglycerides, and LDL-cholesterol are predictive of coronary events, CV events, and for triglyceride and low-density lipoprotein cholesterol variability, incident diabetes. The mechanisms accounting for these associations remain to be determined

Recent advances in understanding the regulation of metalloproteinases [version 1; referees: 2 approved]

Metalloproteinases remain important players in arthritic disease, in part because members of this large enzymatic family, namely matrix metalloproteinase-1 (MMP-1) and MMP-13, are responsible for the irreversible degradation of articular cartilage collagen. Although direct inhibition of MMPs fell out of vogue with the initial clinical disappointment of the first generation of compounds, interest in other mechanisms that control these important enzymes has always been maintained. Since these enzymes are critically important for tissue homeostasis, their expression and activity are tightly regulated at many levels, not just by direct inhibition by their endogenous inhibitors the tissue inhibitors of metalloproteinases (TIMPs). Focussing on MMP-13, we discuss recent work that highlights new discoveries in the transcriptional regulation of this enzyme, from defined promoter functional analysis to how more global technologies can provide insight into the enzyme’s regulation, especially by epigenetic mechanisms, including non-coding RNAs. In terms of protein regulation, we highlight recent findings into enzymatic cascades involved in MMP-13 regulation and activation. Importantly, we highlight a series of recent studies that describe how MMP-13 activity, and in fact that of other metalloproteinases, is in part controlled by receptor-mediated endocytosis. Together, these new discoveries provide a plethora of novel regulatory mechanisms, besides direct inhibition, which with renewed vigour could provide further therapeutic opportunities for regulating the activity of this class of important enzymes

The function of microRNAs in cartilage and osteoarthritis

MicroRNAs are small double-stranded RNAs, which negatively regulate gene expression and have been shown to have key roles in both chondrocyte development and cartilage homeostasis with age. Deletion of all microRNAs in chondrocytes leads to skeletal growth defects in mice, whilst deletion of specific mi croRNAs, e.g. miR-140, leads to premature articular cartilage degradation and increased susceptibility to posttraumatic osteoarthritis. Studies comparing microRNA expression in normal human articular cartilage compared to osteoarthritic cartilage show differential expression, but varying sample groups make interpretation difficult. MicroRNAs have been proposed as circulating biomarkers of osteoarthritis, but again, this differs amongst patient cohorts. Many micro- RNAs have been shown to have roles in chondrocyte phenotype via signaling pathways, apoptosis, autophagy and senescence. Modulating microRNAs in the joint has been shown to reduce osteoarthritis in animal models and translating this to man as a novel therapeutic strategy will be key

Long non-coding RNA ROCR contributes to SOX9 expression and chondrogenic differentiation of human mesenchymal stem cells

Long non-coding RNAs (lncRNAs) are expressed in a highly tissue-specific manner where they function in various aspects of cell biology, often as key regulators of gene expression. In this study we established a role for lncRNAs in chondrocyte differentiation. Using RNA sequencing we identified a human articular chondrocyte repertoire of lncRNAs from normal hip cartilage donated by neck of femur fracture patients. Of particular interest are lncRNAs upstream of the master chondrocyte transcription factor SOX9 locus. SOX9 is an HMG-box transcription factor which is essential for chondrocyte development by directing the expression of chondrocyte specific genes. Two of these lncRNAs are upregulated during chondrogenic differentiation of MSCs. Depletion of one of these lncRNA, LOC102723505, which we termed ROCR (regulator of chondrogenesis RNA), by RNAi disrupted MSC chondrogenesis, concomitant with reduced cartilage-specific gene expression and incomplete matrix component production, indicating an important role in chondrocyte biology. Specifically, SOX9 induction was significantly ablated in the absence of ROCR, and overexpression of SOX9 rescued the differentiation of MSCs into chondrocytes. Our work sheds further light on chondrocyte specific SOX9 expression and highlights a novel method of chondrocyte gene regulation involving a lncRNA

Effects of dalcetrapib in patients with a recent acute coronary syndrome

In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes