Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine

Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.     

HEAT TRANSFER BETWEEN ROUGH SURFACES IN CONTACT OVER A HIGHLY ELLIPTICAL CONTOUR AREA: COMPARISON OF EXPERIMENTAL AND NUMERICAL RESULTS

This paper describes experimental and numerical studies of heat transfer between surfaces in contact over a highly elliptical area in a gas or in vacuum. Measurements of the steady-state thermal resistance of a high aspect ratio contact formed between cylindrical steel surfaces with widely different radii of curvature (76 cm vs 0.95 cm) are reported for two levels of surface roughness (0.05 μm and 1.0 μm rms) and compared to 3-D numerical results obtained with the multigrid method. Theoretical results obtained by evaluating the contact conductance acting over each surface element within the contour area with a method developed previously for rough but nominally flat surfaces are shown to be in excellent agreement with the rough surface experimental data.     

Stability of nonlinear 2D systems described by the continuous-time Roesser model

This paper considers systems with two-dimensional dynamics (2D systems) described by the continuous-time nonlinear state-space Roesser model. The sufficient conditions of exponential stability in terms of vector Lyapunov functions are established. These conditions are then applied to analysis of the absolute stability of a certain class of systems comprising a linear continuous-time plant in the form of the Roesser model with a nonlinear characteristic in the feedback loop, which satisfies quadratic constraints. The absolute stability conditions are reduced to computable expressions in the form of linear matrix inequalities. The obtained results are extended to the class of continuous-time systems governed by the Roesser model with Markovian switching. The problems of absolute stability and stabilization via state- and output-feedback are solved for linear systems of the above class. The solution procedures for these problems are in the form of algorithms based on linear matrix inequalities.     

Dis-Bond Detection and the Possibility of Interfacial Stiffness Measurement with Real-Time Impulsive Stimulated Thermal Scattering

We describe a new, real-time, noninvasive method for dis-bond (delamination) detection which is based on a technique known as impulsive stimulated thermal scattering (ISTS). We first explain the ISTS technique and compare data from polyimide films tightly bound to silicon substrates with data from unsupported polyimide films. The observed differences in the data from these two cases are readily understandable and offer an unmistakable signature for delaminations. We demonstrate ISTS dis-bond detection by locating and mapping out randomly-distributed and spatially-fine regions of delamination in a polyimide film-silicon substrate system. Finally, we present two simple physical models of the interfacial region which comprehensively describe acoustic data from the tightly-bound and the unsupported samples. With insight from simulations using these models, we suggest how ISTS might be used to determine interfacial adhesion quality and we show how ISTS sensitivity to interfacial effects can be adjusted.     

The composition of volatile oils derived from oleoresins

Essential oils and oleoresins derived from spices and herbs, by steam distillation in the former case or by solvent extraction in the latter case, are increasingly more important as flavoring constituents in heat-processed foods. Steam-distilled oils, when used for such purposes, tend to steam-distill during the heat processing due to moisture that is present. Oleoresins that contain the essential oil and natural fixatives tend to depress this volatilization and are preferred as flavoring materials in such cases. Subjective flavor panel evaluations are reported, showing the significance between oleoresins and essential oils as well as the corresponding spice or herb. Instrumental evaluation, primarily gas chromatography, will compare essential oils produced by direct steam distillation vs. those isolated form oleoresins. The difference in composition which can be related to the improved flavor effect from oleoresins is discussed. One of 13 papers presented in the symposium “Flavor Research in Fats and Fat Bearing foods,” AOCS Meeting, Atlantic City, October 1971.     

The Effects of Experience and Strategy on Visual Attention Allocation in an Automated Multiple-Task Environment

Operators and users interacting with computer environments often have to deal with multiple tasks at once, responding to each in series. Diagnostic automation, that is, automation that alerts users when and where to look, has been suggested to support the unique challenges of multiple task environments: activating tasks, switching between tasks, and tasks interfering with each other. Automation is not always reliable, however. Because of the common interaction with novel systems and the importance of training, the Simultaneous Task Environment Platform program—a multiple-task environment—was developed to understand the effects of experience on interaction with these automation-supported systems, as well as what strategies were developed. It was found that participants became more efficient with experience only when they interacted with higher reliability automation. Furthermore, the strategies participants developed focused on the differences between tasks and patterns across those tasks. Automated systems training should be sure to employ these findings.     

Restoration of depressed prostanoid-induced ileal contraction in spontaneously hypertensive rats by dietary fish oil

We have reported that dietary fish oil (FO) rich in n-3 PUFA modulates gut contractility. It was further demonstrated that the gut of spontaneously hypertensive rats (SHR) has a depressed contractility response to prostaglandins (PG) compared with normotensive Wistar-Kyoto (WKY) rats. We investigated whether feeding diets supplemented with n-3 PUFA increased gut contractility and restored the depressed prostanoid response in SHR gut. Thirteen-week-old SHR were fed diets containing fat at 5 g/100 g as coconut oil (CO), lard, canola oil containing 10% (w/w) n-3 FA as alpha-linolenic acid (1 8:3n-3), or FO (as HiDHA, 22:6n-3) for 12 wk. A control WKY group was fed 5 g/100 g CO in the diet. As confirmed, the SHR CO group had a significantly lower gut response to PGE2 and PGF2alpha compared with the WKY CO group. Feeding FO increased the maximal contraction response to acetylcholine in the ileum compared with all diets and in the colon compared with lard, and restored the depressed response to PGE2 and PGF2alpha in the ileum but not the colon of SHR. FO feeding also led to a significant increase in gut total phospholipid n-3 PUFA as DHA (22:6n-3) with lower n-6 PUFA as arachidonic acid (20:4n-6). Canola feeding led to a small increase in ileal EPA (20:5n-3) and DHA and in colonic DHA without affecting contractility. However, there was no change in ileal membrane muscarinic binding properties due to FO feeding. This report confirms that dietary FO increases muscarinic- and eicosanoid receptor-induced contractility in ileum and that the depressed prostanoid response in SHR ileum, but not colon, is restored by tissue incorporation of DHA as the active nutrient.     

Single-channel EEG measurement of engagement in virtual rehabilitation: a validation study

Virtual Reality - Stroke rehabilitation suffers from low levels of patient engagement, impeding recovery. Virtual rehabilitation (VR) approaches can improve patient outcomes; however, there is...     

Antioxidant Activity of Osage Orange Extract in Soybean Oil and Fish Oil during Storage

The food industry is seeking natural antioxidants for edible oils that have comparable activity to synthetic counterparts. In this study, Osage orange extract (OOE) rich in osajin (42.9%) and pomiferin (30.0%) was obtained after hexane extraction of the fruit, and its antioxidant activity was examined in stripped soybean oil (SBO) and fish oil (FO), in which antioxidants and polar compounds were removed. The antioxidant activity of OOE was compared with commercial natural antioxidants (i.e., rosemary extract and mixed tocopherols) and a synthetic antioxidant, butylated hydroxytoluene (BHT), during storage at 25 and 40 °C. The 0.1% OOE had stronger antioxidant activity than 0.1% rosemary extract and 0.1% mixed tocopherols in both oils at 25 and 40 °C. Its activity was similar to 0.02% BHT in SBO and was similar or slightly stronger than 0.02% BHT in FO. When OOE was studied at 0.05, 0.1, and 0.2%, there was a weak dose–response in SBO but a stronger dose–response in FO. Headspace volatile analysis using solid phase micro-extraction (SPME) combined with GC–MS indicated that 0.1% OOE was very effective in preventing the formation of volatile oxidation products in both oils. Although it should be further tested for safety before the actual use, this study shows that OOE can be developed as an antioxidant for edible oils.     

Using a conductive sphere as a probe to characterize the sensitivity of soft piezoresistive films

Flexible piezoresistive films, such as, carbon black/polydimethylsiloxane (C-PDMS) composites, are often used as skin analogs and integrated into complex array sensors for tactile sensing. The uniformity of the sensor characteristics heavily depends on the homogeneity of the composite. Therefore, the ability to locally characterize a film that will be integrated into a complex force sensor could be critical. Here, a method to characterize the local sensitivity of flexible piezoresistive films is presented. Using a conductive sphere, which was chosen over a flat probe to eliminate misalignment issues, the surface of a thin film composite is indented to characterize the change in resistivity in terms of average strain. Experiments were performed with 15 and 18 wt% carbon black C-PDMS films of varying thickness. The contact radius of the probe with the piezoresistive film was estimated using the Johnson-Roberts-Kendall contact theory. Theoretical contact area estimates were found to agree with contact radius measurements carried out using optically transparent PDMS films observed through an optical microscope. Results show that C-PDMS with 15 wt% carbon black exhibit a higher rate if change of resistivity and gauge factor than films of same thickness with 18 wt% carbon black. On the other hand, thicker films exhibit higher gauge factors for the two tested carbon black contents. Tests carried out at multiple locations yielded consistent sensitivity values, making these types of composites suitable for array type force sensors.