Delivering Bio-Mems & Microfluidic Education Around Accessible Technologies

Electronic Systems are now being deployed in al-most all aspects of daily life as opposed to being confined to consumer electronics, computing, communication and control applications as was the case in the 90’s. One of the more significant growth areas is medical instrumentation, health care, bio-chemical analysis and environmental monitoring. Most of these applications will in the future require the integration of fluidics and biology within complex electronic systems. We are now seeing technologies emerging together with access services such as the FP6 “INTEGRAMplus” and “MicroBuilder” programs that offer competitive solutions for companies wishing to de-sign and prototype microfluidic systems. For successful deployment of these systems, a new breed of electronic engineers are needed that understand how to deliver bio-chemistry and living cells to transducers and integrate the required technologies reliably into robust systems. This paper will report on initial training initiatives now active under the INTEGRAMplus program

Dive Patterns of Belugas (Delphinapterus leucas) in Waters Near Eastern Devon Island

Data were obtained for six belugas or white whales (Delphinapterus leucas) instrumented with satellite-linked dive recorders in September-November 1995 in waters near eastern Devon Island, Canada. The mean of the daily maximum depths of dives was 483-665 m for the 31-51 days when maximum depth measurements were taken. The deepest dive recorded was 872 m. Both the dive rate (number of dives per hour to depths > 8 m) and the time at surface (time spent within the uppermost 5 m of the water column) declined from mid-September through mid-October. The four females had significantly elevated dive rates during the nights (2300-0500), whereas the males showed no effects of time of day on the dive rates. Few dives lasted more than 18 min, and most lasted either less than 1 min or for 9-18 min. A trend from short dives to longer dives was noted from mid-September through October, along with a decline in the number of dives to 8-20 m and a corresponding increase in the number of dives to 200-452 m during the same period. The small whales made more dives and had longer times at the surface than the large whales, but they did not dive as deeply or for as long periods as did the large whales. Vertical speeds ranged from .05 ms to .19 ms for depths of 52-800 m. These speeds are significantly faster than vertical speeds recorded from narwhals (Monodon monoceros).En septembre-novembre 1995, on a recueilli des données sur six bélugas ou dauphins blancs (Delphinapterus leucas) équipés d'enregistreurs de plongée en liaison avec un satellite, dans les eaux proches de la partie est de l'île Devon au Canada. La moyenne quotidienne de la profondeur maximale des plongées était de 483 à 665 m pour les 31 à 51 jours durant lesquels on a mesuré la profondeur maximale. La plongée la plus profonde enregistrée était de 872 m. De mi-septembre à mi-octobre, le taux de plongée (nombre de plongées par heure à des profondeurs > à 8 m), de même que le temps en surface (temps passé dans les 5 m supérieurs de la colonne d'eau) ont diminué. Les quatre femelles affichaient un taux de plongée nettement supérieur durant la nuit (de 23 h à 5 h), tandis que le taux de plongée des mâles n'était pas affecté par le moment de la journée. Peu de plongées duraient plus de 18 mn et la plupart duraient soit moins d'une minute, soit de 9 à 18 mn. De mi-septembre à fin octobre, on a noté une tendance à la hausse dans la durée des plongées, parallèlement à une baisse du nombre de plongées entre 8 et 20 m de profondeur et une augmentation correspondante du nombre de plongées entre 200 et 452 m au cours de la même période. Pour les petits dauphins blancs, le nombre de plongées et la durée des périodes passées en surface étaient plus grands que pour les gros dauphins. Les vitesses verticales allaient de 0,5 m/s à 1,9 m/s pour des profondeurs allant de 52 à 800 m. Ces vitesses sont notablement plus rapides que les vitesses verticales enregistrées pour les narvals (Monodon monoceros)

Differences in coronary flow and myocardial metabolism at rest and during pacing between patients with obstructive and patients with nonobstructive hypertrophic cardiomyopathy

Fifty patients with hypertrophic cardiomyopathy underwent invasive study of coronary and myocardial hemodynamics in the basal state and during the stress of pacing. The 23 patients with basal obstruction (average left ventricular outflow gradient, 77 ± 33 mm Hg; left ventricular systolic pressure, 196 ± 33 mm Hg, mean ± 1 SD) had significantly lower coronary resistance (0.85 ± 0.18 versus 1.32 ± 0.44 mm Hg min/ml, p < 0.001) and higher basal coronary flow (106 ± 20 versus 80 ± 25 ml/min, p < 0.001) in the anterior left ventricle, associated with higher regional myocardial oxygen consumption (12.4 ± 3.6 versus 8.9 ± 3.3 ml oxygen/min, p < 0.001) compared with the 27 patients without obstruction (mean left ventricular systolic pressure 134 ± 18 mm Hg, p < 0.001).Myocardial oxygen consumption and coronary blood flow were also significantly higher at paced heart rates of 100 and 130 beats/min (the anginal threshold for 41 of the 50 patients) in patients with obstruction compared with those without. In patients with obstruction, transmural coronary flow reserve was exhausted at a heart rate of 130 beats/min; higher heart rates resulted in more severe metabolic evidence of ischemia with all patients experiencing chest pain, associated with an actual increase in coronary resistance. Patients without obstruction also demonstrated evidence of ischemia at heart rates of 130 and 150 beats/min, with 25 of 27 patients experiencing chest pain. In this group, myocardial ischemia occurred at significantly lower coronary flow, higher coronary resistance and lower myocardial oxygen consumption, suggesting more severely impaired flow delivery in this group compared with those with obstruction. Abnormalities in myocardial oxygen extraction and marked elevation in filling pressures during stress were noted in both groups.Thus, obstruction to left ventricular outflow is associated with high left ventricular systolic pressure and oxygen consumption and therefore has important pathogenetic importance to the precipitation of ischemia in patients with hypertrophic cardiomyopathy. Patients without obstruction may have greater impairment in coronary flow delivery during stress

POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients.

PURPOSE: The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)-positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform-sparing PI3 kinase inhibitor. PATIENTS AND METHODS: 30 patients with ER-positive, metastatic breast cancer who had failed prior endocrine therapy were treated with escalating doses of taselisib (2 or 4 mg in an intermittent or continuous schedule) combined with tamoxifen 20 mg once daily in this phase 1b study using a "rolling six" design. RESULTS: Taselisib combined with tamoxifen was generally well tolerated, with treatment-emergent adverse events as expected for this class of drugs, including diarrhea (13 patients, 43%), mucositis (10 patients, 33%), and hyperglycemia (8 patients, 27%). No dose-limiting toxicities were observed. Objective responses were seen in 6 of 25 patients with RECIST-measurable disease (ORR 24%). Median time to disease progression was 3.7 months. Twelve of 30 patients (40%) had disease control for 6 months or more. Circulating tumor (ct)DNA studies using next-generation tagged amplicon sequencing identified early indications of treatment response and mechanistically relevant correlates of clinical drug resistance (e.g., mutations in KRAS, ERBB2) in some patients. CONCLUSIONS: Taselisib can be safely combined with tamoxifen at the recommended phase 2 dose of 4 mg given once daily on a continuous schedule. Preliminary evidence of antitumor activity was seen in both PIK3CA mutant and wild-type cancers. The randomized phase 2 part of POSEIDON (testing tamoxifen plus taselisib or placebo) is currently recruiting

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Test support strategies for MEMS

Integrated test technology is becoming critically important for MEMS due to the high reliability and safety critical applications targeted. High quality levels in production require efficient test strategies that are properly validated. Fault simulation and testability analysis are critical utilities required to support this process. This paper will discuss methods for achieving test support based on the extension of tools and techniques currently being introduced into the mixed signal ASIC market

Fault-free and fault modelling of MEMS devices

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