Large-Scale Integration of Nanoelectromechanical Systems for Gas Sensing Applications

We have developed arrays of nanomechanical systems (NEMS) by large-scale integration, comprising thousands of individual nanoresonators with densities of up to 6 million NEMS per square centimeter. The individual NEMS devices are electrically coupled using a combined series-parallel configuration that is extremely robust with respect to lithographical defects and mechanical or electrostatic-discharge damage. Given the large number of connected nanoresonators, the arrays are able to handle extremely high input powers (>1 W per array, corresponding to <1 mW per nanoresonator) without excessive heating or deterioration of resonance response. We demonstrate the utility of integrated NEMS arrays as high-performance chemical vapor sensors, detecting a part-per-billion concentration of a chemical warfare simulant within only a 2 s exposure period

Permo-Triassic Deposits: from shallow water to base of slope

Conference on the Geology of Oman, Muscat, Oman, Field Guidebook A0

HCI as a means to prosociality in the economy

HCI research often involves intervening in the economic lives of people, but researchers only rarely give explicit consideration to what actually constitutes prosociality in the economy. Much has been said previously regarding sustainability but this has largely focused on environmental rather than interpersonal relations. This paper provides an analysis of how prosocial HCI has been discussed and continues to be defined as a research field. Based on a corpus of published works, we describe a variety of genres of work relating to prosocial HCI. Key intellectual differences are explored, including the epistemological and ethical positions involved in designing for prosocial outcomes as well as how HCI researchers posit economic decision-making. Finally, emerging issues and opportunities for further debate and collaboration are discussed in turn

Responsiveness of the Eating Disorders Quality of Life Scale (EDQLS) in a longitudinal multi-site sample

<p>Abstract</p> <p>Background</p> <p>In eating disorders (EDs), treatment outcome measurement has traditionally focused on symptom reduction rather than functioning or quality of life (QoL). The Eating Disorders Quality of Life Scale (EDQLS) was recently developed to allow for measurement of broader outcomes. We examined responsiveness of the EDQLS in a longitudinal multi-site study.</p> <p>Methods</p> <p>The EDQLS and comparator generic QoL scales were collected in person at baseline, and 3 and 6 months from 130 participants (mean age 25.6 years; range 14-60) in 12 treatment programs in four Canadian provinces. Total score differences across the time points and responsiveness were examined using both anchor- and distribution-based methods.</p> <p>Results</p> <p>98 (75%) and 85 (65%) responses were received at 3 and 6 months respectively. No statistically significant differences were found between the baseline sample and those lost to follow-up on any measured characteristic. Mean EDQLS total scores increased from 110 (SD = 24) to 124.5 (SD = 29) at 3 months and 129 (SD = 28) at 6 months, and the difference by time was tested using a general linear model (GLM) to account for repeated measurement (p < .001). Responsiveness was good overall (Cohen's d = .61 and .80), and confirmed using anchor methods across 5 levels of self-reported improvement in health status (p < .001). Effect sizes across time were moderate or large for for all age groups. Internal consistency (Chronbach's alpha=.96) held across measurement points and patterns of responsiveness held across subscales. EDQLS responsiveness exceeded that of the Quality of Life Inventory, the Short Form-12 (mental and physical subscales) and was similar to the 16-dimension quality of life scale.</p> <p>Conclusions</p> <p>The EDQLS is responsive to change in geographically diverse and clinically heterogeneous programs over a relatively short time period in adolescents and adults. It shows promise as an outcome measure for both research and clinical practice.</p

A specific nanobody prevents amyloidogenesis of D76N β2-microglobulin in vitro and modifies its tissue distribution in vivo

Systemic amyloidosis is caused by misfolding and aggregation of globular proteins in vivo for which effective treatments are urgently needed. Inhibition of protein self-aggregation represents an attractive therapeutic strategy. Studies on the amyloidogenic variant of β2-microglobulin, D76N, causing hereditary systemic amyloidosis, have become particularly relevant since fibrils are formed in vitro in physiologically relevant conditions. Here we compare the potency of two previously described inhibitors of wild type β2-microglobulin fibrillogenesis, doxycycline and single domain antibodies (nanobodies). The β2-microglobulin -binding nanobody, Nb24, more potently inhibits D76N β2-microglobulin fibrillogenesis than doxycycline with complete abrogation of fibril formation. In β2-microglobulin knock out mice, the D76N β2-microglobulin/ Nb24 pre-formed complex, is cleared from the circulation at the same rate as the uncomplexed protein; however, the analysis of tissue distribution reveals that the interaction with the antibody reduces the concentration of the variant protein in the heart but does not modify the tissue distribution of wild type β2-microglobulin. These findings strongly support the potential therapeutic use of this antibody in the treatment of systemic amyloidosis

Plasminogen activation triggers transthyretin amyloidogenesis in vitro

Systemic amyloidosis is a usually fatal disease caused by extracellular accumulation of abnormal protein fibers, amyloid fibrils, derived by misfolding and aggregation of soluble globular plasma protein precursors. Both WT and genetic variants of the normal plasma protein transthyretin (TTR) form amyloid, but neither the misfolding leading to fibrillogenesis nor the anatomical localization of TTR amyloid deposition are understood. We have previously shown that, under physiological conditions, trypsin cleaves human TTR in a mechano-enzymatic mechanism that generates abundant amyloid fibrils in vitro. In sharp contrast, the widely used in vitro model of denaturation and aggregation of TTR by prolonged exposure to pH 4.0 yields almost no clearly defined amyloid fibrils. However, the exclusive duodenal location of trypsin means that this enzyme cannot contribute to systemic extracellular TTR amyloid deposition in vivo. Here, we therefore conducted a bioinformatics search for systemically active tryptic proteases with appropriate tissue distribution, which unexpectedly identified plasmin as the leading candidate. We confirmed that plasmin, just as trypsin, selectively cleaves human TTR between residues 48 and 49 under physiological conditions in vitro. Truncated and full-length protomers are then released from the native homotetramer and rapidly aggregate into abundant fibrils indistinguishable from ex vivo TTR amyloid. Our findings suggest that physiological fibrinolysis is likely to play a critical role in TTR amyloid formation in vivo. Identification of this surprising intersection between two hitherto unrelated pathways opens new avenues for elucidating the mechanisms of TTR amyloidosis, for seeking susceptibility risk factors, and for therapeutic innovation

Angiolymphoid hyperplasia with eosinophilia: efficacy of isotretinoin?

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign but potentially disfiguring vascular lesion. It is usually characterized by dermal and subcutaneous nodules, primarily in the head and neck region. Spontaneous regression is common, but persistent or recurrent lesions may require treatment. Several treatments have been reported but surgery is the most efficient one. METHODS AND RESULTS: We report a 32-year-old man presenting with multiple nodules on the cheeks, preauricular region and the scalp and who received treatment with isotretinoin (0.5 mg/kg/day) for 1 year with complete resolution of one of his scalp nodules. The rest of the lesions remained stable and were treated with surgical excision without recurrence. CONCLUSION: Isotretinoin may play a role in the treatment of ALHE due to its antiangiogenic properties via a reduction of vascular endothelial growth factor (VEGF) production by keratinocytes