Dynamics of Ionizable Polymers in Ionic Liquid (IL) using Nuclear Magnetic Resonance Spectroscopy

https://tigerprints.clemson.edu/csrp/1001/thumbnail.jp

Towards on-chip tunable nanolasers based on optomechanical zipper cavities

Work towards semiconductor nanolasers at λ = 1.3 μm in optomechanically coupled one dimensional photonic-crystal cavities is presented. Optical mode spectroscopy and on-chip tuning capability based on capacitive actuation is developed. Experimental and theoretical results are presented

A chip-scale integrated cavity-electro-optomechanics platform

We present an integrated optomechanical and electromechanical nanocavity, in which a common mechanical degree of freedom is coupled to an ultrahigh-Q photonic crystal defect cavity and an electrical circuit. The sys- tem allows for wide-range, fast electrical tuning of the optical nanocavity resonances, and for electrical control of optical radiation pressure back-action effects such as mechanical amplification (phonon lasing), cooling, and stiffening. These sort of integrated devices offer a new means to efficiently interconvert weak microwave and optical signals, and are expected to pave the way for a new class of micro-sensors utilizing optomechanical back-action for thermal noise reduction and low-noise optical read-out.Comment: 11 pages, 7 figure

Actuation of Micro-Optomechanical Systems Via Cavity-Enhanced Optical Dipole Forces

We demonstrate a new type of optomechanical system employing a movable, micron-scale waveguide evanescently-coupled to a high-Q optical microresonator. Micron-scale displacements of the waveguide are observed for milliwatt(mW)-level optical input powers. Measurement of the spatial variation of the force on the waveguide indicates that it arises from a cavity-enhanced optical dipole force due to the stored optical field of the resonator. This force is used to realize an all-optical tunable filter operating with sub-mW control power. A theoretical model of the system shows the maximum achievable force to be independent of the intrinsic Q of the optical resonator and to scale inversely with the cavity mode volume, suggesting that such forces may become even more effective as devices approach the nanoscale.Comment: 4 pages, 5 figures. High resolution version available at (http://copilot.caltech.edu/publications/CEODF_hires.pdf). For associated movie, see (http://copilot.caltech.edu/research/optical_forces/index.htm

Duloxetine in the treatment of major depressive disorder: an open-label study

<p>Abstract</p> <p>Background</p> <p>Major depressive disorder (MDD) is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE) may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined.</p> <p>Methods</p> <p>Patients (N = 533) meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD]) for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD₁₇) total score ≥18 and a Clinical Global Impression of Severity (CGI-S) score ≥4 at baseline. Efficacy measures included the HAMD₁₇total score, HAMD₁₇subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS). Quality of life was assessed using the Sheehan Disability Scale (SDS) and the Quality of Life in Depression Scale (QLDS). Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF) scale.</p> <p>Results</p> <p>The rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by ≥10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD₁₇, CGI-S) the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment.</p> <p>Conclusion</p> <p>In this open-label phase of a relapse prevention study, duloxetine (60 mg QD) was shown to be safe and effective in the treatment of MDD.</p> <p>Trial registration</p> <p>NCT00036309.</p

Advances in small lasers

M.T.H was supported by an Australian Research council Future Fellowship research grant for this work. M.C.G. is grateful to the Scottish Funding Council (via SUPA) for financial support.Small lasers have dimensions or modes sizes close to or smaller than the wavelength of emitted light. In recent years there has been significant progress towards reducing the size and improving the characteristics of these devices. This work has been led primarily by the innovative use of new materials and cavity designs. This Review summarizes some of the latest developments, particularly in metallic and plasmonic lasers, improvements in small dielectric lasers, and the emerging area of small bio-compatible or bio-derived lasers. We examine the different approaches employed to reduce size and how they result in significant differences in the final device, particularly between metal- and dielectric-cavity lasers. We also present potential applications for the various forms of small lasers, and indicate where further developments are required.PostprintPeer reviewe

Treatment patterns associated with Duloxetine and Venlafaxine use for Major Depressive Disorder

<p>Abstract</p> <p>Background</p> <p>Duloxetine and venlafaxine extended release (venlafaxine XR) are SNRIs indicated for the treatment of MDD. This study addresses whether duloxetine and venlafaxine XR are interchangeable in their patterns of use with patients who are depressed or are used more selectively based on treatment history, background characteristics, and presenting symptoms.</p> <p>Methods</p> <p>This was a retrospective analysis of an administrative insurance claims database. We studied patients in managed care with major depressive disorder (MDD) treated with duloxetine or venlafaxine XR. Predictors of treatment and cost were assessed using Chi-square and logistic regression analyses of demographics and past-year medication use and comorbidities.</p> <p>Results</p> <p>Patients with MDD treated with duloxetine (n = 9,641) versus venlafaxine XR (n = 8,514) tended to be older, slightly more likely to be female, and treated by a psychiatrist (<it>P </it>< 0.0001). In the prior year, more duloxetine patients (vs. venlafaxine XR) received ≥3 unique antidepressants (20.8% vs. 16.6%), ≥3 unique pain medications (25.5% vs. 15.6%), and had ≥8 unique diagnosed comorbid medical and psychiatric conditions (38.6% vs. 29.1%). The prior 6-month total health care costs were $1,731 higher for duloxetine than for venlafaxine XR and declined for both medications in the 6 months after treatment began. Logistic regression analysis revealed that 61% of duloxetine patients and 61% of venlafaxine XR patients were predictable from prior patient and treatment factors.</p> <p>Conclusions</p> <p>Patients with MDD treated with duloxetine tended to have a more complex and costly antecedent clinical presentation compared with venlafaxine XR patients, suggesting that physicians do not use the medications interchangeably.</p

Absolute Single-Molecule Entropies from Quasi-Harmonic Analysis of Microsecond Molecular Dynamics: Correction Terms and Convergence Properties

The convergence properties of the absolute single-molecule configurational entropy and the correction terms used to estimate it are investigated using microsecond molecular dynamics simulation of a peptide test system and an improved methodology. The results are compared with previous applications for systems of diverse chemical nature. It is shown that (i) the effect of anharmonicity is small, (ii) the effect of pairwise correlation is typically large, and (iii) the latter affects to a larger extent the entropy estimate of thermodynamic states characterized by a higher motional correlation. The causes of such deviations from a quasi-harmonic behavior are explained. This improved approach provides entropies also for molecular systems undergoing conformational transitions and characterized by highly frustrated energy surfaces, thus not limited to systems sampling a single quasi-harmonic basin. Overall, this study emphasizes the need for extensive phase-space sampling in order to obtain a reliable estimation of entropic contributions

Hyperdimensional Analysis of Amino Acid Pair Distributions in Proteins

Our manuscript presents a novel approach to protein structure analyses. We have organized an 8-dimensional data cube with protein 3D-structural information from 8706 high-resolution non-redundant protein-chains with the aim of identifying packing rules at the amino acid pair level. The cube contains information about amino acid type, solvent accessibility, spatial and sequence distance, secondary structure and sequence length. We are able to pose structural queries to the data cube using program ProPack. The response is a 1, 2 or 3D graph. Whereas the response is of a statistical nature, the user can obtain an instant list of all PDB-structures where such pair is found. The user may select a particular structure, which is displayed highlighting the pair in question. The user may pose millions of different queries and for each one he will receive the answer in a few seconds. In order to demonstrate the capabilities of the data cube as well as the programs, we have selected well known structural features, disulphide bridges and salt bridges, where we illustrate how the queries are posed, and how answers are given. Motifs involving cysteines such as disulphide bridges, zinc-fingers and iron-sulfur clusters are clearly identified and differentiated. ProPack also reveals that whereas pairs of Lys residues virtually never appear in close spatial proximity, pairs of Arg are abundant and appear at close spatial distance, contrasting the belief that electrostatic repulsion would prevent this juxtaposition and that Arg-Lys is perceived as a conservative mutation. The presented programs can find and visualize novel packing preferences in proteins structures allowing the user to unravel correlations between pairs of amino acids. The new tools allow the user to view statistical information and visualize instantly the structures that underpin the statistical information, which is far from trivial with most other SW tools for protein structure analysis

Mutation D816V Alters the Internal Structure and Dynamics of c-KIT Receptor Cytoplasmic Region: Implications for Dimerization and Activation Mechanisms

The type III receptor tyrosine kinase (RTK) KIT plays a crucial role in the transmission of cellular signals through phosphorylation events that are associated with a switching of the protein conformation between inactive and active states. D816V KIT mutation is associated with various pathologies including mastocytosis and cancers. D816V-mutated KIT is constitutively active, and resistant to treatment with the anti-cancer drug Imatinib. To elucidate the activating molecular mechanism of this mutation, we applied a multi-approach procedure combining molecular dynamics (MD) simulations, normal modes analysis (NMA) and binding site prediction. Multiple 50-ns MD simulations of wild-type KIT and its mutant D816V were recorded using the inactive auto-inhibited structure of the protein, characteristic of type III RTKs. Computed free energy differences enabled us to quantify the impact of D816V on protein stability in the inactive state. We evidenced a local structural alteration of the activation loop (A-loop) upon mutation, and a long-range structural re-organization of the juxta-membrane region (JMR) followed by a weakening of the interaction network with the kinase domain. A thorough normal mode analysis of several MD conformations led to a plausible molecular rationale to propose that JMR is able to depart its auto-inhibitory position more easily in the mutant than in wild-type KIT and is thus able to promote kinase mutant dimerization without the need for extra-cellular ligand binding. Pocket detection at the surface of NMA-displaced conformations finally revealed that detachment of JMR from the kinase domain in the mutant was sufficient to open an access to the catalytic and substrate binding sites