Hybrid nanoscale patterning strategies combine the registration and addressability of conventional lithographic techniques with the chemical and physical functionality enabled by intermolecular, electrostatic and/or biological interactions. This review aims to highlight and to provide a comprehensive description of recent developments in hybrid nanoscale patterning strategies that enhance existing lithographic techniques or can be used to fabricate functional chemical patterns that interact with their environment. These functional structures create new capabilities, such as the fabrication of physicochemical surfaces that can recognize and capture analytes from complex liquid or gaseous mixtures. The nanolithographic techniques we describe can be classified into three general areas: traditional lithography, soft lithography and scanning-probe lithography. The strengths and limitations of each hybrid patterning technique will be discussed, along with the current and potential applications of the resulting patterned, functional surfaces.

We applied system identification to the analysis of fluctuations in heart rate (HR), arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize quantitatively the physiological mechanisms responsible for the couplings between these variables. We characterized two autonomically mediated coupling mechanisms [the heart rate baroreflex (HR baroreflex) and respiratory sinus arrhythmia (ILV-HR)] and two mechanically mediated coupling mechanisms [the blood pressure wavelet generated with each cardiac contraction (circulatory mechanics) and the direct mechanical effects of respiration on blood pressure (ILV-->ABP)]. We evaluated the method in humans studied in the supine and standing postures under control conditions and under conditions of beta-sympathetic and parasympathetic pharmacological blockades. Combined beta-sympathetic and parasympathetic blockade abolished the autonomically mediated couplings while preserving the mechanically mediated coupling. Selective autonomic blockade and postural changes also altered the couplings in a manner consistent with known physiological mechanisms. System identification is an "inverse-modeling" technique that provides a means for creating a closed-loop model of cardiovascular regulation for an individual subject without altering the underlying physiological control mechanisms.

Background-Spinal cord stimulation (SCS) reduces the incidence of ventricular tachyarrhythmias in experimental models. This study investigated the effects of long-term SCS on ventricular function in a postinfarction canine heart failure model. Methods and Results-In stage 1, dogs underwent implantable cardioverter-defibrillator implantation and embolization of the left anterior descending artery followed by right ventricular pacing (240 ppm) for 3 weeks to produce heart failure. In stage 2, 28 surviving animals were assigned to the SCS (delivered at the T4/T5 spinal region for 2 hours 3 times a day), medicine (MED; carvedilol therapy at 12.5 mg PO BID), or control (CTRL; no therapy) group for the initial phase 1 study. In a subsequent phase 2 study, 32 stage 1 survivors were equally randomized to the SCS, MEDS (carvedilol plus ramipril 2.5 mg PO QD), SCS plus MEDS (concurrent therapy), or CTRL group. Animals were monitored for 5 weeks (phase 1) or 10 weeks (phase 2). In stage 3, all phase 1 animals underwent circumflex artery balloon occlusion for 1 hour. In the SCS group, left ventricular ejection fraction was 65Ϯ5% at baseline, 17Ϯ3% at the end of stage 1, and 47Ϯ7% at the end of stage 2. In the MED group, left ventricular ejection fraction was 61Ϯ4% at baseline, 18Ϯ3% at the end of stage 1, and 34Ϯ4% at the end of stage 2. In the CTRL group, left ventricular ejection fraction was 64Ϯ5% at baseline, 19Ϯ5% at the end of stage 1, and 28Ϯ3% at the end of stage 2. Left ventricular ejection fraction was significantly improved in the SCS compared with the MED and CTRL groups (PϽ0.001 for both). The mean number of spontaneous nonsustained ventricular tachyarrhythmias during stage 2 and the occurrence of ischemic ventricular tachyarrhythmias during stage 3 also were significantly decreased in the SCS (27Ϯ17 and 27%, respectively; PϽ0.03) and MED (58Ϯ42 and 33%; PϽ0.05) versus CTRL (88Ϯ52 and 76%) group. After 10 weeks in the phase 2 studies, the greatest recovery in ejection fraction was noted in the SCS (52Ϯ5%) and SCSϩMEDS (46Ϯ4%) groups compared with the MEDS (38Ϯ2%) and CTRL (31Ϯ4%) groups. Conclusion-SCS

A series of nanoscale chemical patterning methods based on soft and hybrid nanolithographies have been characterized using scanning electron microscopy with corroborating evidence from scanning tunneling microscopy and lateral force microscopy. We demonstrate and discuss the unique advantages of the scanning electron microscope as an analytical tool to image chemical patterns of molecules highly diluted within a host self-assembled monolayer and to distinguish regions of differential mass coverage in patterned self-assembled monolayers. We show that the relative contrast of self-assembled monolayer patterns in scanning electron micrographs depends on the operating primary electron beam voltage, monolayer composition, and monolayer order, suggesting that secondary electron emission and scattering can be used to elucidate chemical patterns.