General Purpose Computer (GPC) to GPC systems interface description

The General Purpose Computer (GPC) 'subsystem' of the Orbiter Data Processing System was described. Two interface areas are discussed. One is the area of GPC intraconnections and intracommunications involving the hardware/software interface between the Central Processing Unit (CPU) and the Input/Output Processor (IOP). The other is the area of GPC interconnections and intercommunications and involves the hardware/software interface between the five Orbiter GPC's. Based on the detailed GPC interface given, it is felt that the basic CPU to IOP interface and the GPC to GPC interface have the potential for trouble free operation. However, due to the complexity of the interface and the criticality of GPC synchronization to overall avionics performance, the GPC to GPC interface should be carefully evaluated when attempting to resolve test anomalies that may involve GPC timing and synchronization errors

Everything you Want to Know and Never Dared to ask:A Practical Approach to Employing Challenge-Based Learning in Engineering Ethics

Challenge-based learning (CBL) for engineering ethics tasks students with identifying ethical challenges in cooperation with an external partner, e.g., a technology company. As many best-practice parameters of such courses remain unclear, this contribution focuses on a teacher-centric introduction into deploying CBL for engineering ethics. Taking Goodlad's curriculum typology as a point of departure, we discuss practical issues in devising, maintaining and evaluating CBL courses for engineering ethics both in terms of the temporal dimension (before, during and after the course) as well as in terms of the people involved. We will discuss selecting learning objectives, forms of knowledge acquisition, supporting self-organization, and fostering discursive etiquette, as well as cooperative, yet critical attitudes. Additionally, we will delve into strategic matters, e.g., ways to approach potential external partners and maintain fruitful cooperations.</p

Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct.

Vasopressin and vasopressin antagonists are finding expanded use in mouse models of disease and in clinical medicine. To provide further insight into the physiological role of V1a and V2 vasopressin receptors in the human and mouse kidney, intrarenal localization of the receptors mRNA was determined by in situ hybridization. V2-receptor mRNA was predominantly expressed in the medulla, whereas mRNA for V1a receptors predominated in the cortex. The segmental localization of vasopressin-receptor mRNAs was determined using simultaneous in situ hybridization and immunohistochemistry for segment-specific markers, including aquaporin-2, Dolichos biflorus agglutinin, epithelial Na channels, Tamm Horsfall glycoprotein, and thiazide-sensitive Na(+)-Cl(-) cotransporter. Notably, V1a receptor expression was exclusively expressed in V-ATPase/anion exchanger-1-labeled alpha-intercalated cells of the medullary collecting duct in both mouse and human kidney. In cortical collecting ducts, V1a mRNA was more widespread and detected in both principal and intercalated cells. V2-receptor mRNA is diffusely expressed along the collecting ducts in both mouse and human kidney, with higher expression levels in the medulla. These results demonstrate heterogenous axial expression of both V1a and V2 vasopressin receptors along the human and mouse collecting duct. The restricted expression of V1a-receptor mRNA in intercalated cells suggests a role for this receptor in acid-base balance. These findings further suggest distinct regulation of renal transport function by AVP through V1a and V2 receptors in the cortex vs. the medulla

Pathological and Transcriptome Changes in the ReninAAV db/db uNx Model of Advanced Diabetic Kidney Disease Exhibit Features of Human Disease

The ReninAAV db/db uNx model of diabetic kidney disease (DKD) exhibits hallmarks of advanced human disease, including progressive elevations in albuminuria and serum creatinine, loss of glomerular filtration rate, and pathological changes. Microarray analysis of renal transcriptome changes were more similar to human DKD when compared to db/db eNOS−/− model. The model responds to treatment with arterial pressure lowering (lisinopril) or glycemic control (rosiglitazone) at early stages of disease. We hypothesized the ReninAAV db/db uNx model with advanced disease would have residual disease after treatment with lisinopril, rosiglitazone, or combination of both. To test this, ReninAAV db/db uNx mice with advanced disease were treated with lisinopril, rosiglitazone, or combination of both for 10 weeks. All treatment groups showed significant lowering of urinary albumin to creatinine ratio compared to baseline; however, only combination group exhibited lowering of serum creatinine. Treatment improved renal pathological scores compared to baseline values with residual disease evident in all treatment groups when compared to db/m controls. Gene expression analysis by TaqMan supported pathological changes with increased fibrotic and inflammatory markers. The results further validate this model of DKD in which residual disease is present when treated with agents to lower arterial pressure and glycemic control

Fluorescence-Based Functional Assay for Wnt/-Catenin Signaling Activity

Aberrant activation of beta-catenin signaling has been implicated in the development of human cancers. As a Wnt signal transducer, beta-catenin forms a complex with the lymphocyte enhancer-binding factor/T cell factor transcription factor and activates downstream targets that promote cell proliferation. Here we developed a Wnt-dependent beta-catenin-mediated heterologous transactivation system, which consisted of a chimeric transcription factor constructed by fusing the GAL4 DNA-binding domain with the full-length beta-catenin, and a GAL4-responsive reporter expressing GFP. The chimeric transcription factor was highly unstable and exerted no detectable transactivating effect on the GAL4-responsive reporter. However, lithium and Wnt1 significantly stabilized this chimeric transactivator, indicating that this transactivation system is regulated by beta-catenin in a Wnt-responsive fashion. Thus, this transactivation system could be used as a functional reporter to identify potential upstream factors that deregulate beta-catenin signaling during tumorigenesis, as well as to screen for potential anti-cancer agents that specifically inhibit beta-catenin signaling in human tumors

Patient Characteristics Associated with Sexual Interest and Activity Among Adults with Spina Bifida

ObjectiveTo identify factors associated with sexual interest and activity among adults with spina bifida and to describe the sexual profile of those who were sexually active. Sexual health of adults with spina bifida is often neglected and current knowledge on the topic is limited.MethodsAn anonymous web-based survey was advertised and administered between March 2018 and September 2018 and participants 16&nbsp;years and older with spina bifida were included in this study. Respondents were asked about sexual interest, activity, and function using the validated Patient-Reported Outcomes Measurement Information System Sexual Function Profile. Bivariate and multivariable models with ordinal logistic regression were fitted to evaluate predictors of sexual interest and sexual function.ResultsOf the 261 respondents with a self-reported diagnosis of spina bifida (mean age of 38.5&nbsp;years), 73.2% noted at least a little bit of interest in sexual activity. In multivariate analysis, women were less likely to report higher sexual interest than men (odds ratio (OR)&nbsp;=&nbsp;0.53, 95% CI 0.31-0.92, P&nbsp;=&nbsp;.03) whereas those with higher physical functioning were more likely to have higher sexual interest (OR&nbsp;=&nbsp;1.04, confidence interval (CI) 1.01-1.07, P&nbsp;=&nbsp;.03). Just less than half of respondents (46.4%) were sexually active in the past 30&nbsp;days, and those with a ventriculoperitoneal shunt were less likely to engage in sexual activity compared to those without (OR&nbsp;=&nbsp;0.36, 95% CI 0.19-0.68; P&nbsp;&lt;.01).ConclusionThe mismatch between sexual interest and sexual activity highlights the importance of exploring issues related to sexual health when counseling adult patients with spina bifida