NONLINEAR INSTABILITIES IN MEM/NEM ELECTROSTATIC SWITCHES

The aim of this thesis is to develop suitable mathematical models for the purpose of investigating nonlinear instabilities in Micro-Electro-Mechanical (MEM) and Nano- Electro-Mechanical (NEM) electrostatic switches. The proposed models capture the influence of electric field fringing, intermolecular forces, surface stress and surface elasticity. Based on Euler-Bernoulli assumptions, a surface elasticity model and the generalized Young-Laplace equation, effects of surface stress and surface elasticity are incorporated in the models, while the intermolecular force effects are modelled using quantum mechanics. The derived governing equation representing static pull-in behaviour of switches is inherently nonlinear due to the driving electrostatic force and intermolecular forces which become dominant at nanoscale. Since no exact solutions are available for the resulting nonlinear differential equation, an approach based on homotopy perturbation method (HPM) is proposed to construct approximate analytical solutions, as well as to characterize the instability behaviour. Numerical solutions obtained via finite difference method (FDM) are employed for validating the analytical results. HPM in conjunction with Adomian decomposition method (ADM) has been employed for approximate analytical predictions. To this end, the solutions for the fourth-order two- point boundary value problem (BVP) representing MEM/NEM electrostatic switches are constructed in terms of a convergent series. The pull-in parameters, including pull-in voltage, detachment length and low-voltage actuation windows, are investigated in detail using the above methods and also via a lumped parameter model. HPM analytical solutions are found to be more accurate and reliable compared to those predicted via the lumped parameter model. HPM solutions also tend to overestimate the static deflection, and underestimate pull-in voltage and detachment length compared to the FDM numerical solutions. However, its relative differences to the FDM numerical solutions are within an acceptable range for design purposes. HPM is concluded to work well for the static pull-in in parameter determination, and is preferred since it is straightforward to implement and could save computation efforts while not losing accuracy. Predictions via HPM and FDM also revealed that the influence of surface effects on the pull-in instability of MEM/NEM switches is significant and the exclusion of surface effects in the analysis may result in an erroneous estimation of the pull-in parameters. Further, the concept of Casimir actuated switches is proposed for the purpose of ensuring the physical realization of a new class of the switchable devices using pure Casmir force actuation. To this end, a new idea of Casimir-force actuation window has been introduced for the purpose of ensuring designs that yield functional Casimir actuated switches. The present study is envisaged to be beneficial for the design and applications of MEM/NEM electrostatic as well as Casimir actuated switches. The methodology presented in this thesis may be also used for the analysis of actuation systems, which may involve other types of nonlinear actuation forces

ChoiceMates: Supporting Unfamiliar Online Decision-Making with Multi-Agent Conversational Interactions

Unfamiliar decisions -- decisions where people lack adequate domain knowledge or expertise -- specifically increase the complexity and uncertainty of the process of searching for, understanding, and making decisions with online information. Through our formative study (n=14), we observed users' challenges in accessing diverse perspectives, identifying relevant information, and deciding the right moment to make the final decision. We present ChoiceMates, a system that enables conversations with a dynamic set of LLM-powered agents for a holistic domain understanding and efficient discovery and management of information to make decisions. Agents, as opinionated personas, flexibly join the conversation, not only providing responses but also conversing among themselves to elicit each agent's preferences. Our between-subjects study (n=36) comparing ChoiceMates to conventional web search and single-agent showed that ChoiceMates was more helpful in discovering, diving deeper, and managing information compared to Web with higher confidence. We also describe how participants utilized multi-agent conversations in their decision-making process

Oral Transmucosal Delivery of Fentanyl Citrate for Breakthrough Cancer Pain Relief

Episodes of breakthrough cancer pain are relatively common occurrences for patients undergoing cancer treatments. Characterized by pain unrestrained by traditional medications, these physical burdens impose a significant degree of suffering. In order to control and eliminate this pain, Actiq, a pharmaceutical lollipop, has been developed to provide rapid oral transmucosal delivery of fentanyl citrate, a potent medicinal narcotic. To elucidate the pharmacokinetics of the drug under various dosages, a computer model of fentanyl diffusion in the oral cavity was designed in COMSOL. Upon solving the model process, concentration profiles of fentanyl in the mucosa over time were developed for various dosages. Sensitivity analyses were also performed to determine the effects of several parameters on fentanyl diffusion. The resulting concentration profiles showed that peak concentrations of 0.00079 g/m3, 0.0016 g/m3, and 0.0032 g/m3 for 200 ?g, 400 ?g, and 800 ?g dosages, respectively, were achieved at approximately 800 seconds. Additionally, based upon the sensitivity analyses, the fentanyl solubility and the lollipop radial dissolution rate have the greatest impact on fentanyl concentration and diffusion. Future research can be performed to optimize the drug diffusion by altering these two parameters, ultimately yielding a more effective Actiq product

The FANCD2-FANCI complex is recruited to DNA interstrand crosslinks before monoubiquitination of FANCD2

The Fanconi Anemia (FA) pathway is important for the repair of DNA interstrand crosslinks (ICL). The FANCD2-FANCI complex is central to the pathway, and localizes to ICLs dependent on its monoubiquitination. It has remained elusive whether the complex is recruited before or after the critical monoubiquitination. Here we report the first structural insight into the human FANCD2-FANCI complex by obtaining the cryo- EM structure. The complex contains an inner cavity, large enough to accommodate a double stranded DNA helix, as well as a protruding Tower domain. Disease-causing mutations in the Tower domain is observed in several FA patients. Our work reveals that recruitment of the complex to a stalled replication fork serves as the trigger for the activating monoubiquitination event. Taken together, our results uncover the mechanism of how the FANCD2-FANCI complex activates the FA pathway, and explains the underlying molecular defect in FA patients with mutations in the Tower domain

Terahertz generation in Czochralski grown periodically poled Mg:Y:LiNbO3 via optical rectification

Using a canonical pump-probe experimental technique, we studied the terahertz (THz) waves generation and detection via optical rectification and mixing in Czochralski-grown periodically poled Mg:Y:LiNbO3 (PPLN) crystals. THz waves with frequencies at 1.37 THz and 0.68 THz as well as 1.8 THz were obtained for PPLN with nonlinear grating periods of 0.03 and 0.06 mm, respectively. A general theoretical model was developed by considering the dispersion and damping of low frequency phonon-polariton mode. Our results show that THz waves are generated in forward and backward directions via pumping pulse rectification. The generated THz waves depend on the spectral shape of the laser pulses, quasi-phase mismatches and dispersion characteristics of a crystal.Comment: 25 pages, 4 figure

Epithelial Migration and Non-adhesive Periderm Are Required for Digit Separation during Mammalian Development.

The fusion of digits or toes, syndactyly, can be part of complex syndromes, including van der Woude syndrome. A subset of van der Woude cases is caused by dominant-negative mutations in the epithelial transcription factor Grainyhead like-3 (GRHL3), and Grhl3-/-mice have soft-tissue syndactyly. Although impaired interdigital cell death of mesenchymal cells causes syndactyly in multiple genetic mutants, Grhl3-/- embryos had normal interdigital cell death, suggesting alternative mechanisms for syndactyly. We found that in digit separation, the overlying epidermis forms a migrating interdigital epithelial tongue (IET) when the epithelium invaginates to separate the digits. Normally, the non-adhesive surface periderm allows the IET to bifurcate as the digits separate. In contrast, in Grhl3-/- embryos, the IET moves normally between the digits but fails to bifurcate because of abnormal adhesion of the periderm. Our study identifies epidermal developmental processes required for digit separation

3D-Printed Hand Controlled by Arm Gestures to Verify the Robustness and Reliability of a Low Cost Surface Electromyography System

The study focuses on the development of a low-cost surface electromyography and 3D-printed hand gesture-recognition system. The complete system captures four (4) channels of EMG data through sEMG amplifier circuits interfaced to an Arduino prototyping board. This data is sent to a workstation wherein the graphical user interface shows the pre-processed signal. The gestures are used as control for the movements of the 3D-printed arm

The Lyman-alpha forest at redshifts 0.1 -- 1.6: good agreement between a large hydrodynamic simulation and HST spectra

We give a comprehensive statistical description of the Lyman-alpha absorption from the intergalactic medium in a hydrodynamic simulation at redshifts 0.1-1.6, the range of redshifts covered by HST spectra of QSOs. We use the ENZO code to make a 76 comoving Mpc cube simulation using 75 kpc cells, for a Hubble constant of 71 km/s/Mpc. The best prior work, by \citet{dave99},used an SPH simulation in a 15.6 Mpc box with an effective resolution of 245 kpc and slightly different cosmological parameters. At redshifts z=2 this simulation is different from data. \citet{tytler07b} found that the simulated spectra at z=2 have too little power on large scales, Lyman-alpha lines are too wide, there is a lack high column density lines, and there is a lack of pixels with low flux. Here we present statistics at z<1.6, including the flux distribution, the mean flux, the effective opacity, and the power and correlation of the flux. We also give statistics of the lyman alpha lines including the line width distribution, the column density distribution, the number of lines per unit equivalent width and redshift, and the correlation between the line width and column density. We find that the mean amount of absorption in the simulated spectra changes smoothly with redshift with DA(z)=0.01(1+z)^{2.25}. Both the trend and absolute values are close to measurements of HST spectra by \citet{kirkman07a}. The column density and line width distributions are also close to those measured from HST spectra by \citet{janknecht06a}, except for the mode of the line width distribution which is smaller in the HST spectra. Although some differences that we saw at z=2 are too subtle to be seen in existing HST spectra, overall, the simulation gives an good description of HST spectra at 0.1<z<1.6

Deletion of the hemopexin or heme oxygenase-2 gene aggravates brain injury following stroma-free hemoglobin-induced intracerebral hemorrhage

BACKGROUND: Following intracerebral hemorrhage (ICH), red blood cells release massive amounts of toxic heme that causes local brain injury. Hemopexin (Hpx) has the highest binding affinity to heme and participates in its transport, while heme oxygenase 2 (HO2) is the rate-limiting enzyme for the degradation of heme. Microglia are the resident macrophages in the brain; however, the significance and role of HO2 and Hpx on microglial clearance of the toxic heme (iron-protoporphyrin IX) after ICH still remain understudied. Accordingly, we postulated that global deletion of constitutive HO2 or Hpx would lead to worsening of ICH outcomes. METHODS: Intracerebral injection of stroma-free hemoglobin (SFHb) was used in our study to induce ICH. Hpx knockout (Hpx(−/−)) or HO2 knockout (HO2(−/−)) mice were injected with 10 μL of SFHb in the striatum. After injection, behavioral/functional tests were performed, along with anatomical analyses. Iron deposition and neuronal degeneration were depicted by Perls’ and Fluoro-Jade B staining, respectively. Immunohistochemistry with anti-ionized calcium-binding adapter protein 1 (Iba1) was used to estimate activated microglial cells around the injured site. RESULTS: This study shows that deleting Hpx or HO2 aggravated SFHb-induced brain injury. Compared to wild-type littermates, larger lesion volumes were observed in Hpx(−/−) and HO2(−/−) mice, which also bear more degenerating neurons in the peri-lesion area 24 h postinjection. Fewer Iba1-positive microglial cells were detected at the peri-lesion area in Hpx(−/−) and HO2(−/−) mice, interestingly, which is associated with markedly increased iron-positive microglial cells. Moreover, the Iba1-positive microglial cells increased from 24 to 72 h postinjection and were accompanied with improved neurologic deficits in Hpx(−/−) and HO2(−/−) mice. These results suggest that Iba1-positive microglial cells could engulf the extracellular SFHb and provide protective effects after ICH. We then treated cultured primary microglial cells with SFHb at low and high concentrations. The results show that microglial cells actively take up the extracellular SFHb. Of interest, we also found that iron overload in microglia significantly reduces the Iba1 expression level and resultantly inhibits microglial phagocytosis. CONCLUSIONS: This study suggests that microglial cells contribute to hemoglobin-heme clearance after ICH; however, the resultant iron overloads in microglia appear to decrease Iba1 expression and to further inhibit microglial phagocytosis

Functional dissection of the R domain of cystic fibrosis transmembrane conductance regulator1The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked `advertisement' in accordance.1

AbstractExogenously expressed unphosphorylated sub-domains of the R domain block CFTR Cl− channels in the planar lipid bilayer, though the block differs from block with full length R domain. Full length R domain peptide (aa 588–855) blocks CFTR Cl− channels quickly, completely and permanently [1]. Two sub-domains, RD1RD2 (aa 588–805) and RD2TM (aa 672–855), also inhibit CFTR Cl− channels, but the block takes longer to effect and is not complete. Shorter sequences, RD1 (aa 588–746) and RD2 (aa 672–805), fail to effect any block. These data suggest that either the amino-terminal or carboxy-terminal portions of the R domain protein or its stabilized secondary structure are critical to functional regulation