Browsing by Author "Wang, Yin"
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- Enzyme-Triggered Chemodynamic Therapy via a Peptide-H2S Donor Conjugate with Complexed Fe2+Zhu, Yumeng; Archer, William R.; Morales, Katlyn F.; Schulz, Michael D.; Wang, Yin; Matson, John B. (Wiley-V C H Verlag, 2023-04)Inducing high levels of reactive oxygen species (ROS) inside tumor cells is a cancer therapy method termed chemodynamic therapy (CDT). Relying on delivery of Fenton reaction promoters such as Fe2+, CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide-H2S donor conjugate, complexed with Fe2+, termed AAN-PTC-Fe2+. The AAN tripeptide was specifically cleaved by legumain, an enzyme overexpressed in glioma cells, to release carbonyl sulfide (COS). Hydrolysis of COS by carbonic anhydrase formed H2S, an inhibitor of catalase, an enzyme that detoxifies H2O2. Fe2+ and H2S together increased intracellular ROS levels and decreased viability in C6 glioma cells compared with controls lacking either Fe2+, the AAN sequence, or the ability to generate H2S. AAN-PTC-Fe2+ performed better than temezolimide while exhibiting no cytotoxicity toward H9C2 cardiomyocytes. This study provides an H2S-amplified, enzyme-responsive platform for synergistic cancer treatment.
- Pulse width modulated resonant power conversion(United States Patent and Trademark Office, 2014-08-19)A power converter including a resonant circuit is controlled by pulse width modulation (PWM) of a switching circuit to control current in the resonant circuit near the frequency of the resonant circuit (a null-immittance criterion) in order to control current and voltage at the output of the resonant circuit. Further control of voltage can be performed by PWM of a switching circuit at the output of the resonant circuit such that centers of the duty cycles of respective switches for the output of the resonant circuit are substantially synchronized and substantially symmetrical about centers of said duty cycles of respective switches at the input of the resonant circuit. Thus, operation of the converter is substantially simplified by using only PWM, a wide range of input and output voltages can be achieved and the converter circuit can be configured for bi-directional power transfer.
- Self-Oscillating Unified Linearizing ModulatorWang, Yin (Virginia Tech, 2012-10-31)The continuous conduction mode (CCM) boost, buck-boost and buck-boost derived pulse-width modulation dc-dc converters suffer from the large-signal control-to-output nonlinearity. Without feedback control, the large-signal control-to-output nonlinearity would lead to output overregulation and even damage the components. The control gain is defined as the ratio of output voltage to control signal. The small-signal control gain is defined as differentiating output voltage with respect to control signal. Feedback control helps to make the output trace the reference signal. A large-signal control-to-output linearity is established. Compared with open loop control, the feedback loop design is complex; and the feedback control might suffer from the instability caused by the negative small-signal control gain, which is due to the loss and parasitic in practice. Except feedback control, open loop linearization methods can also realize the large-signal control-to-output linearity. A modulated-ramp pulse-width modulation generator is introduced in [6]. A current source works as the control signal. A capacitor is charged by the current source, whose voltage works as the carrier and compared with a constant dc bias voltage to determine the duty cycle. When applying this method to boost, buck-boost and buck-boost derived PWM dc-dc converters, a large-signal control-to-output linearity is established. However, the control gain is dependent on the input voltage; it cannot maintain constant when input voltage varies. A feedforward pulse width modulator is introduced in [39] to realize a large-signal control-to-output linearity. The static conversion ratio is divided into numerator and denominator as the functions of duty cycle. An integrator with reset clock signal helps to determine the right timing. The control gain is ideally constant and independent of input voltage. However, the mismatch between the integrator time constant and the switching period would result in a nonlinear control gain, which is dependent on the input voltage. In the thesis work, a self-oscillating unified linearizing modulator is introduced. It first provides a unified procedure to establish a large-signal control-to-output linearity for different pulse-width modulation dc-dc converters. Feedforward is employed to mitigate the impact from line voltage. Self-oscillation is adopted to provide the internal clock signal and to determine the switching frequency. A constant control gain is obtained, independent on the input voltage or the mismatch between clock signals. The modulator is constructed by three simple and standard building blocks. With the considerations of parasitic components and loss, how to design the constant gain, which excludes the negative small-signal control gain within the entire control signal range, is analyzed and discussed. The performance of this self-oscillating unified linearizing modulator is verified by experiments. The impacts from propagation delay in practical components are taken into considerations, which improves the quality of generated signals. Combined with a boost converter, a good large-signal control-to-output linearization is demonstrated. In the future work, the small-signal control-to-output transfer function is first deduced based on the SOUL modulator. Bode plots show the unique characteristic based on the SOUL modulator compared with the conventional modulator. Next, the impacts from this unique characteristic to feedback loop design and dynamic performance are discussed.
- Supramolecular Peptide Nanostructures Regulate Catalytic Efficiency and SelectivityLi, Zhao; Joshi, Soumil Y.; Wang, Yin; Deshmukh, Sanket A.; Matson, John B. (Wiley-V C H, 2023-05)We report three constitutionally isomeric tetrapeptides, each comprising one glutamic acid (E) residue, one histidine (H) residue, and two lysine (K-S) residues functionalized with side-chain hydrophobic S-aroylthiooxime (SATO) groups. Depending on the order of amino acids, these amphiphilic peptides self-assembled in aqueous solution into different nanostructures:nanoribbons, a mixture of nanotoroids and nanoribbons, or nanocoils. Each nanostructure catalyzed hydrolysis of a model substrate, with the nanocoils exhibiting the greatest rate enhancement and the highest enzymatic efficiency. Coarse-grained molecular dynamics simulations, analyzed with unsupervised machine learning, revealed clusters of H residues in hydrophobic pockets along the outer edge of the nanocoils, providing insight for the observed catalytic rate enhancement. Finally, all three supramolecular nanostructures catalyzed hydrolysis of the l-substrate only when a pair of enantiomeric Boc-l/d-Phe-ONp substrates were tested. This study highlights how subtle molecular-level changes can influence supramolecular nanostructures, and ultimately affect catalytic efficiency.