Ultrathin TiN Membranes as a Technology Platform for CMOS‐Integrated MEMS and BioMEMS Devices

A standard complementary metal‐oxide‐semiconductor (CMOS) process is successfully modified to encompass the preparation of suspended TiN membranes of only 50 nm thickness from one of the metal layer stacks of the back‐end flow. The layers’ elastomechanical constants are determined with high precision by laser Doppler vibrometry. Residual stress gradients are compensated and a state of moderate tensile strain is introduced into the membranes. Test systems of TiN beams and bridges operating in a capacitive coupling scheme are optimized for the low voltage range attainable with CMOS devices. TiN actuators are particularly suited for applications in biotechnology like sensing of pressure or viscosity in microfluidic devices due to their high corrosion resistance in liquid electrolyte surroundings. The established inclusion of the process in a CMOS pilot line enables the production of cheap and monolithically integrated microelectromechanical systems (MEMS) and bio‐microelectromechanical systems (BioMEMS) devices.     

Side effects of flux enhancing chemicals in membrane bioreactors (MBRs): study on their biological toxicity and their residual fouling propensity

Soluble and colloidal materials like soluble microbial products (SMP) or extracellular polymeric substances (EPS) are considered to be major foulants in membrane bioreactors (MBRs). Removing these fouling causing substances is thus thought to reduce the fouling of the membrane in general.In addition to traditional strategies for fouling prevention which mostly try to remedy the effects of fouling by air scour, etc., the new and promising method of adding chemicals is being investigated here. Previous tests with 30 different substances have shown that several of these reduce SMP concentration in the supernatant and enhance filtration. Nevertheless, additive dosing might have unknown side effects in filtration systems. Results presented in this study indicate that these additives may themselves cause severe fouling on different membranes if they remain unbound in the liquid phase. Therefore, the thorough control of the dosing rate of these chemicals will be of paramount importance in full scale applications. Biological toxicity of additives was measured in terms of respiration. OUR tests did not show inhibiting effects for most additives. Chitosan even showed an enhanced OUR due to biodegradability. Oxygen transfer could be enhanced for 25% with the addition of a polymer.     

Novelty detection and segmentation based on Gaussian mixture models: A case study in 3D robotic laser mapping

This article proposes a framework to detect and segment changes in robotics datasets, using 3D robotic mapping as a case study. The problem is very relevant in several application domains, not necessarily related with mobile robotics, including security, health, industry and military applications. The aim is to identify significant changes by comparing current data with previous data provided by sensors. This feature is extremely challenging because large amounts of noisy data must be processed in a feasible way. The proposed framework deals with novelty detection and segmentation in robotic maps using clusters provided by Gaussian Mixture Models (GMMs). GMMs provides a feature space that enables data compression and effective processing. Two alternative criteria to detect changes in the GMM space are compared: a greedy technique based on the Earth Mover’s Distance (EMD); and a structural matching algorithm that fulfills both absolute (global matching) and relative constraints (structural matching). The proposed framework is evaluated with real robotic datasets and compared with other methods known from literature. With this purpose, 3D mapping experiments are carried out with both simulated data and real data from a mobile robot equipped with a 3D range sensor.     

A multiscale systems approach to microelectronic processes

This paper describes applications of molecular simulation to microelectronics processes and the subsequent development of techniques for multiscale simulation and multiscale systems engineering. The progression of the applications of simulation in the semiconductor industry from macroscopic to molecular to multiscale is reviewed. Multiscale systems are presented as an approach that incorporates molecular and multiscale simulation to design processes that control events at the molecular scale while simultaneously optimizing all length scales from the molecular to the macroscopic. It is discussed how design and control problems in microelectronics and nanotechnology, including the targeted design of processes and products at the molecular scale, can be addressed using the multiscale systems tools. This provides a framework for addressing the “grand challenge” of nanotechnology: how to move nanoscale science and technology from art to an engineering discipline.     

Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf-1/mitogen-activated protein kinase pathway activation

Cell attachment to fibronectin stimulates the integrin-dependent interaction of p85-associated phosphatidylinositol (PI) 3-kinase with integrin-dependent focal adhesion kinase (FAK) as well as activation of the Ras/mitogen-activated protein (MAP) kinase pathway. However, it is not known if this PI 3-kinase-FAK interaction increases the synthesis of the 3-phosphorylated phosphoinositides (3-PPIs) or what role, if any, is played by activated PI 3-kinase in integrin signaling. We demonstrate here the integrin-dependent accumulation of the PI 3-kinase products, PI 3,4-bisphosphate [PI(3,4)P2] and PI(3,4,5)P3, as well as activation of AKT kinase, a serine/threonine kinase that can be stimulated by binding of PI(3,4)P2. The PI 3-kinase inhibitors wortmannin and LY294002 significantly decreased the integrin-induced accumulation of the 3-PPIs and activation of AKT kinase, without having significant effects on the levels of PI(4,5)P2 or tyrosine phosphorylation of paxillin. These inhibitors also reduced cell adhesion/spreading onto fibronectin but had no effect on attachment to polylysine. Interestingly, integrin-mediated Erk-2, Mek-1, and Raf-1 activation, but not Ras-GTP loading, was inhibited at least 80% by wortmannin and LY294002. In support of the pharmacologic results, fibronectin activation of Erk-2 and AKT kinases was completely inhibited by overexpression of a dominant interfering p85 subunit of PI 3-kinase. We conclude that integrin-mediated adhesion to fibronectin results in the accumulation of the PI 3-kinase products PI(3,4)P2 and PI(3,4,5)P3 as well as the PI 3-kinase-dependent activation of the kinases Raf-1, Mek-1, Erk-2, and AKT and that PI 3-kinase may function upstream of Raf-1 but downstream of Ras in integrin activation of Erk-2 MAP and AKT kinases.     

Cognitive arithmetic and problem solving: a comparison of children with specific and general mathematics difficulties

This study examined problem-solving and number-fact skills in two subgroups of third-grade children with mathematics difficulties (MD): MD-specific (n = 12) and MD-general (n = 12). The MD-specific group had difficulties in mathematics but not in reading, and the MD-general group had difficulties in reading as well as in mathematics. A comparison group of nonimpaired children (n = 24) also was included. The findings showed that on both story and number-fact problems, the MD-specific group performed worse than the nonimpaired group in timed conditions but not in untimed conditions. The MD-general group, on the other hand, performed worse than the nonimpaired group, regardless of whether tasks were timed or not. An analysis of children's strategies in untimed conditions showed that both the MD-specific and the MD-general groups relied more on backup strategies than the nonimpaired group. However, children in the MD-specific group executed backup strategies more skillfully than children in the MD-general group, allowing them to achieve parity with children in the nonimpaired group when tasks were not timed. The findings suggest that children with specific MD have circumscribed deficits associated with fact retrieval, whereas children with general MD have more basic delays associated with problem conceptualization and execution of calculation procedures.     

Thromboembolism after foot and ankle surgery. A multicenter study

Thromboembolic disease presents a potentially fatal complication to patients undergoing orthopaedic surgery. Although the incidence after hip and knee surgery has been studied and documented, its incidence after surgery of the foot and ankle is unknown. For this reason, a prospective multicenter study was undertaken to identify patients with clinically evident thromboembolic disease to evaluate potential risk factors. Two thousand seven hundred thirty-three patients were evaluated for preoperative risk factors and postoperative thromboembolic events. There were six clinically significant thromboembolic events, including four nonfatal pulmonary emboli, after foot and ankle surgery. The incidence of deep vein thrombosis was six of 2733 (0.22%) and that of nonfatal pulmonary emboli was four of 2733 (0.15%). Factors found to correlate with an increased incidence of deep vein thrombosis were nonweightbearing status and immobilization after surgery. On the basis of these results, routine prophylaxis for thromboembolic disease after foot and ankle surgery probably is not warranted.     

Crystal structure and possible dimerization of the high-potential iron-sulfur protein from Chromatium purpuratum

The crystal structure of the high-potential iron-sulfur protein (HiPIP) isolated from Chromatium purpuratum is reported at 2.7 A resolution. The three HiPIP molecules in the asymmetric unit of the crystals form one and one-half dimers. Two molecules are related by a noncrystallographic symmetry rotation of approximately 175 degrees with negligible translation along the dyad axis. The third molecule in the asymmetric unit also forms a dimer with a second HiPIP molecule across the crystallographic 2-fold symmetry axis. The Fe4S4 clusters in both the crystallographic and noncrystallographic dimers are separated by approximately 13.0 A. Solution studies give mixed results regarding the oligomeric state of the C. purpuratum HiPIP. A comparison with crystal structures of HiPIPs from other species shows that HiPIP tends to associate rather nonspecifically about a conserved, relatively hydrophobic surface patch to form dimers.     

Identification of a series of 1,2,3,4-tetrahydroisoquinolinyl-benzamides with potential anticonvulsant activity

A series of N-(tetrahydroisoquinolinyl)-2-methoxybenzamides was identified by high-throughput screening at the novel SB-204269 binding site. SAR studies have provided compounds 4 and 14 with high affinity and good anticonvulsant activity in animal models.