Exploring design trade-offs for achieving social inclusion in multi-tiered design problems

ABSTRACT

The digital age of the future is ‘not out there to be discovered’, but it needs to be ‘designed’. The design challenge has to address questions about how we want to live, work, and learn (as individuals and as communities) and what we value and appreciate, e.g.: reflecting on quality of life and creating inclusive societies. An overriding design trade-off for the digital age is whether new developments will increase the digital divide or will create more inclusive societies. Sustaining inclusive societies means allowing people of all ages and all abilities to exploit information technologies for personally meaningful activities. Meta-design fosters the design of socio-technical environments that end-user developers can modify and evolve at use time to improve their quality of life and favour their inclusion in the society. This paper describes three case studies in the domain of assistive technologies in which end users themselves cannot act as end-user developers, but someone else (e.g.: a caregiver or a clinician) must accept this role requiring multi-tiered architectures. The design trade-offs and requirements for meta-design identified in the context of the case studies and other researchers’ projects are described to inform the development of future socio-technical environments focused on social inclusion.     

Heat propagation in thermally conductive polymers of PA6 and hexagonal boron nitride

Thermally conductive polymers offer new possibilities for the heat dissipation in electric and electronic components, for example, by a three‐dimensional shaping of the heat sinks. To face safety regulations, improved fire performance of those components is required. In contrast to unfilled polymers, those materials exhibit an entirely different thermal behavior. To investigate the flammability, a phosphorus flame retardant was incorporated into thermally conductive composites of polyamide 6 and hexagonal boron nitride. The flame retardant decreased the thermal conductivity only slightly. However, the burning behavior changed significantly, due to a different heat propagation, which was investigated using a thermographic camera. An optimum content of hexagonal boron nitride for a sufficient thermal conductivity and fire performance was found between 20 and 30 vol%. The improvement of the fire performance was due to a faster heat release out of the pyrolysis zone and an earlier decomposition of the flame retardant. For higher contents of hexagonal boron nitride, the heat was spread faster within the part, promoting an earlier ignition and increasing the decomposition rate of the flame retardant.     

Lignin from Annual Plants as Raw Material Source for Flavors and Basic Chemicals

The enzymatic conversion of lignins, possibly in combination with electrochemical oxidation, makes aromatics such as syringol, guaiacol, vanillin and catechol available in the qualities required by the fragrance industry. The lignins were obtained by soda digestion from wheat straw and Miscanthus, characterized and then converted with laccases. The overall yield amounted up to 9 wt % with a product spectrum confined to four substances. Catechol was the major product, with a fraction of ≈75 %. It can easily be isolated by extraction with acetone.     

Regression of severe atherosclerotic plaque in patients with mild elevation of LDL cholesterol

BACKGROUND: Intensive risk factor reduction in patients with dyslipidemias and coronary atherosclerosis has been shown to result in alterations in coronary artery morphology and reduced clinical events. However, the impact of such interventions in populations with relatively normal levels of low-density lipoproteins (LDL) is unclear. METHODS: To test the hypothesis that intensive risk factor reduction results in angiographic regression in patients with only mildly elevated levels of LDL, 14 patients with angiographically proven coronary atherosclerosis were entered into the University of California Davis Coronary Artery Disease Regression Program and intensively treated with pharmacologic and nonpharmacologic interventions for 2 years. Quantitative angiography was performed prior to and after 2 years of therapy to determine changes in coronary artery diameter. RESULTS: As a result of this program, dietary fat intake was reduced by 58% and LDL fell from 120 +/- 7 mg/dL to 104 +/- 6 mg/dL (p = 0.05). The average diameter of the measured arterial locations (including all 53 stenoses and 292 nondiscrete regions) on study entry was 2.74 +/- 0.05 mm. After 24 months, there was a net increase in arterial diameter (regression) of +0.05 +/- 0.04 mm to 2.81 +/- 0.05 mm (p = 0.01). While there was no significant change in the average diameter of discrete stenoses, all 8 lesions > or = 50% initial diameter narrowing regressed, with a mean diameter change of + 0.2 mm. Conversely, only 1 of 8 mild lesions < or = 20% regressed, while 4 progressed. Intermediate lesions (20% to 50%, n = 37) had balanced progression and regression. CONCLUSIONS: When examined as a continuous variable, there was a significant linear correlation between initial lesion severity (% stenosis) and the extent of regression (mm). Therefore, risk factor reduction (dietary therapy, exercise, psycho-social counseling, and lipid lowering therapy) in patients with only mild dyslipidemia results in angiographic regression of more severe lesions (> 50% initial stenosis), but does not prevent progression of mild lesions (< 20%). These findings demonstrate that intensive risk factor reduction in patients with only mild elevation of lipids beneficially influences the morphology of the most severe lesions.     

Differential transforming growth factor-beta secretion in adenocarcinoma and squamous cell carcinoma of the uterine cervix

Tumor cells from eight freshly isolated cervical cancers (i.e., four adenocarcinomas and four squamous carcinomas) were analyzed for their production of the immune-inhibitory cytokine transforming growth factor-beta (TGF-beta) in vitro. All fresh adenocarcinomas secreted significant levels of TGF-beta (mean 397, range between 207 and 782 pg/ml/10(5) cells/48 hr). In contrast, no detectable TGF-beta was present in the supernatants from the four fresh squamous carcinoma cultures (P < 0.001). These data suggest that major differences in the secretion of the immunoinhibitory cytokine TGF-beta exist between squamous cell carcinomas and adenocarcinomas of the uterine cervix. Furthermore, these findings suggest that at least some of the differences in the natural biologic behavior, as well as in the response to radiation treatment, between these two histologic types of cervical cancer could be related to differences in secretion of this immune-inhibitory cytokine.     

Voluntary head stabilization in space during oscillatory trunk movements in the frontal plane performed in weightlessness

The ability voluntarily to stabilize the head in space during lateral rhythmic oscillations (0.59+/-0.09 Hz) of the trunk has been investigated during microgravity (microG) and normal gravity (nG) conditions (parabolic flights). Five healthy young subjects, who gave informed consent, were examined. The movements were performed with eyes open or eyes closed, during phases of either microG or nG. The main result was that head orientation with respect to vertical may be stabilized about the roll axis under microG with, as well as without vision, despite the reduction in vestibular afferent and muscle proprioceptive inputs. Moreover, the absence of head stabilization about the yaw axis confirms that the degrees of freedom of the neck can be independently controlled, as was previously reported. These results seem to indicate that voluntary head stabilization does not depend crucially upon static vestibular afferents. Head stabilization in space may in fact be organized on the basis of either dynamic vestibular afferents or a short-term memorized postural body schema.     

Structure-permeation relations of met-enkephalin peptide analogues on absorption and secretion mechanisms in Caco-2 monolayers

Due to the low effective permeabilities of peptides at many absorption sites, their structure-permeation relations are of high interest. In this work structure-permeation relations of Met-enkephalin analogues are presented using confluent Caco-2 cells as an in vitro permeation model. Four model peptides (Met-enkephalin, [D-Ala2]Met-enkephalin, [D-Ala2]Met-enkephalinamide, and metkephamid) were tested in terms of permeability, lipophilicity, charge, and molecular size. Permeability coefficients (P(eff)) across Caco-2 cells were low, 3.3 x 10(-8) to 9.5 x 10(-8) cm s-1, and were similar to typical paracellular markers. No correlation of permeability and the log(apparent octanol/buffer partition coefficient) was observed. A 40-fold increase of the permeability of metkephamid in the presence of 10 mM EDTA suggested a significant contribution of paracellular transport. Independent support for this conclusion was obtained by visualizing the pathway of the fluorescein isocyanate isomer I 1-metkephamid by confocal laser scanning microscopy (CLSM). The fluorophore-labeled peptide was observed in the intercallular space only. Metkephamid permeabilities were found to be direction-specific. Permeabilities from basolateral to apical (b-to-a) were significantly higher (ca. 4-fold) than in the opposite (a-to-b) direction. The addition of verapamil equalized the permeabilities in the a-to-b and b-to-a directions, suggesting the involvement of a P-glycoprotein-mediated secretion mechanism. Similar observations were obtained with [D-Ala2]Met-enkephalinamide, but not with Met-enkephalin and [D-Ala2]Met-enkephalin. In contrast to the other analogues, metkephamid and [D-Ala2]Met-enkephalinamide are positively charged at neutral pH, as demonstrated by their isoelectric points (pl = 8.6 for [D-Ala2]Met-enkephalinamide and metkephamid and 5.3 for [D-Ala2]Met-enkephalin and Met-enkephalin). The data is in agreement with the literature showing that most compounds secreted by the P-glycoprotein transporter carry a positive charge.     

Comparison of single-fiber and macro electrode recordings: relationship to motor unit action potential duration

The factors contributing to the duration of a motor unit action potential (MUAP) are believed to be well known, with both manual measurements and computer simulations agreeing with respect to MUAP durations approaching 10 ms. In this investigation, it is clearly demonstrated that use of a wide-open amplifier bandpass combined with signal-to-noise ratio enhancement results in MUAP durations approaching 30 ms recorded with either a macro or single-fiber electrode. Why the clinically recorded MUAP duration differs significantly from these physiologic durations is discussed. A hypothesis is presented whereby the major contributing factor toward MUAP duration is the total time of action potential transmembrane current flow along the muscle fiber from end-plate zone to musculotendinous junction.     

Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.