Electrostatically Tunable Meta-Atoms Integrated With In Situ Fabricated MEMS Cantilever Beam Arrays

Two concentric split ring resonators (SRRs) or meta-atoms designed to have a resonant frequency of 14 GHz are integrated with microelectromechanical systems cantilever arrays to enable electrostatic tuning of the resonant frequency. The entire structure was fabricated monolithically to improve scalability and minimize losses from externally wire-bonded components. A cantilever array was fabricated in the gap of both the inner and outer SRRs and consisted of five evenly spaced beams with lengths ranging from 300 to 400 μm. The cantilevers pulled in between 15 and 24 V depending on the beam geometry. Each pulled-in beam increased the SRR gap capacitance resulting in an overall 1-GHz shift of the measured meta-atom resonant frequency

Pain Management after Cardiac Surgery

Postoperative pain relief is one of the most important concerns for patients undergoing cardiac surgery and is one of the most clinically challenging problems for nurses. It is widely recognized that postoperative pain can negatively impact cardiac surgery outcomes, yet recent surveys report only modest success in pain management as patients continue to describe poorly controlled pain and studies report pain as underestimated, undermedicated, and underrelieved. Research in basic and clinical science has advanced the knowledge of pain management following cardiac surgery. However the emergence of fast-track cardiac surgery programs, which includes tracheal extubation within 6 hours of surgery, early ambulation, a shortened intensive care length of stay and hospital discharge within 3 to 5 days presents a challenge to conventional methods of pain management.Ph.D

Intermolecular NH 2 -/Carboxyl-terminal Interactions in Androgen Receptor Dimerization Revealed by Mutations That Cause Androgen Insensitivity

Structural alignment of the human androgen receptor dimer was investigated by introducing steroid binding domain mutations that cause partial or complete androgen insensitivity into fusion proteins containing the full-length androgen receptor or the steroid binding domain. Most of the mutants had unchanged apparent equilibrium androgen binding affinity and increased dissociation rates of [3H]methyltrienolone and required increased dihydrotestosterone concentrations for transcriptional activation. In a 2-hybrid protein interaction assay in mammalian cells, the steroid binding domain interacts with an NH2-terminal-DNA binding domain fragment and with the full-length androgen receptor at physiological androgen concentrations in a dose-dependent manner. However, mutations at Val-889 and Arg-752 disrupt the NH2-/carboxyl-terminal interaction when introduced into the steroid binding domain fragment but not when present in the full-length androgen receptor. The N-C bimolecular interaction reduces the dissociation rate of bound androgen and slows the degradation rate of the carboxyl-terminal steroid binding domain fragment. The results suggest that steroid binding domain residues Val-889 and Arg-752 are critical to the NH2-/carboxyl-terminal interaction and that an intermolecular N-C interaction occurs during receptor dimerization that results in an antiparallel arrangement of androgen receptor monomers

Evidence for an Anti-parallel Orientation of the Ligand-activated Human Androgen Receptor Dimer

Domain interactions of the human androgen receptor (AR) dimer were investigated using a protein-protein interaction assay in which the NH2- and carboxyl-terminal regions of human AR were fused to the Saccharomyces cerevisiae GAL4 DNA-binding domain and herpes simplex virus VP16 transactivation domain to produce chimeric proteins. Transcriptional activation of a GAL4 luciferase reporter vector up to 100-fold was greater than Fos/Jun leucine zipper binding, indicating stable AR interaction between AR NH2-terminal residues 1-503 and steroid-binding domain residues 624-919 that was specific for and dependent on androgen binding to the steroid-binding domain and was inhibited by anti-androgen binding. Deletion mutagenesis within the NH2-terminal region indicated transactivation domain residues 142-337 were not required for dimerization, whereas deletions near the NH2 terminus (delta 14-150) or NH2-terminal to the DNA-binding domain (delta 339-499) reduced or eliminated the AR interaction, respectively. An NH2-/NH2-terminal interaction was also observed, but no interaction was detected between ligand-free or bound steroid-binding domains. The results indicate that high affinity androgen binding promotes interactions between the NH2-terminal and steroid-binding domains of human AR, raising the possibility of an androgen-induced anti-parallel AR dimer

Maternal high-fat feeding in pregnancy programmes atherosclerotic lesion size in the ApoE*3 Leiden mouse

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high fat diet in utero, programmed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28d postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (p<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol, however transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared to wild-type controls (p=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, p<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol 2-fold higher than in chow fed mothers, p=0.011). The data strongly suggest that maternal hypercholesterolaemia programmes later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models

Maternal high-fat feeding in pregnancy programmes atherosclerotic lesion size in the ApoE*3 Leiden mouse

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high fat diet in utero, programmed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28d postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (p<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol, however transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared to wild-type controls (p=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, p<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol 2-fold higher than in chow fed mothers, p=0.011). The data strongly suggest that maternal hypercholesterolaemia programmes later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models