Network development in biological gels: role in lymphatic vessel development

In this paper, we present a model that explains the prepatterning of lymphatic vessel morphology in collagen gels. This model is derived using the theory of two phase rubber material due to Flory and coworkers and it consists of two coupled fourth order partial differential equations describing the evolution of the collagen volume fraction, and the evolution of the proton concentration in a collagen implant; as described in experiments of Boardman and Swartz (Circ. Res. 92, 801–808, 2003). Using linear stability analysis, we find that above a critical level of proton concentration, spatial patterns form due to small perturbations in the initially uniform steady state. Using a long wavelength reduction, we can reduce the two coupled partial differential equations to one fourth order equation that is very similar to the Cahn–Hilliard equation; however, it has more complex nonlinearities and degeneracies. We present the results of numerical simulations and discuss the biological implications of our model

Dapagliflozin: a sodium glucose cotransporter 2 inhibitor in development for type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a growing worldwide epidemic. Patients face lifelong therapy to control hyperglycemia and prevent the associated complications. There are many medications, with varying mechanisms, available for the treatment of T2DM, but almost all target the declining insulin sensitivity and secretion that are associated with disease progression. Medications with such insulin-dependent mechanisms of action often lose efficacy over time, and there is increasing interest in the development of new antidiabetes medications that are not dependent upon insulin. One such approach is through the inhibition of renal glucose reuptake. Dapagliflozin, the first of a class of selective sodium glucose cotransporter 2 inhibitors, reduces renal glucose reabsorption and is currently under development for the treatment of T2DM. Here, we review the literature relating to the preclinical and clinical development of dapagliflozin

Landscape into architecture William Andrews Nesfield and William Eden Nesfield

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN030213 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The communication bottleneck in knitwear design: Analysis and computing solutions

Communication between different members of a designteam often poses difficulties. This paper reports onthe results of a detailed empirical study ofcommunication in over twenty British, German andItalian knitwear companies. The knitwear designprocess is shared by the designers, who plan thevisual and tactile appearance of the garments, and thetechnicians, who have to realise the garment on aknitting machine. They comprise a typical but smalldesign team whose members have different backgroundsand expertise. Knitwear design allows a detailedanalysis of the causes and effects of communicationbreakdown. Designers specify their designsinaccurately, incompletely and inconsistently;technicians interpret these specifications accordingto their previous experience of similar designs, andproduce garments very different from the designers'original intentions. Knitwear is inherently difficultto describe, as no simple and complete notationexists; and the relationship between visual appearanceand structure and technical properties of knittedfabric is subtle and complex. Designers andtechnicians have different cognitive approaches andare very different people. At the same time theinteraction between designers and technicians is badlymanaged in many companies. This paper argues thatimproving the accuracy and reliability of designers'specifications would significantly enhance the designprocess. It concludes with a description of thearchitecture of an intelligent automatic design systemthat generates technically correct designs from thedesigners' customary notations

Plasma Amyloid-β as a Biomarker in Alzheimer's Disease: The AIBL Study of Aging

Amyloid-β (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to its suitability as an AD biomarker. The objective of this study was to determine the significance of plasma Aβ as an AD biomarker and its relationship with Aβ load and to determine the effect of different assay methods on the interpretation of Aβ levels. Plasma Aβ1-40, Aβ1-42, and N-terminal cleaved fragments were measured using both a commercial multiplex assay and a well-documented ELISA in 1032 individuals drawn from the well-characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Further, Aβ levels were compared to Aβ load derived from positron-emission tomography (PET) with the Pittsburgh compound B (PiB). Lower Aβ1-42 and Aβ1-42/1-40 ratio were observed in patients with AD and inversely correlated with PiB-PET derived Aβ load. However, assay methodology significantly impacted the interpretation of data. The cross-sectional analysis of plasma Aβ isoforms suggests that they may not be sufficient per se to diagnose AD. The value of their measurement in prognosis and monitoring of AD interventions needs further study, in addition to future longitudinal comparisons together with other predictors, which will determine whether plasma Aβ has diagnostic value in a panel of biomarkers