197 results on '"Yi C"'
Search Results
2. Isothermal amplification using sequence-specific fluorescence detection of SARS coronavirus 2 and variants in nasal swabs
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Les Jones, Hemant K Naikare, Yung-Yi C Mosley, and Ralph A Tripp
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COVID-19 Testing ,Molecular Diagnostic Techniques ,SARS-CoV-2 ,COVID-19 ,Humans ,RNA, Viral ,Reverse Transcription ,Nucleic Acid Amplification Techniques ,Sensitivity and Specificity ,General Biochemistry, Genetics and Molecular Biology ,Biotechnology - Abstract
Coronavirus disease 2019 is a public health challenge requiring rapid testing for the detection of infections and transmission. Nucleic acid amplification tests targeting SARS coronavirus 2 (CoV2) are used to detect CoV2 in clinical samples. Real-time reverse transcription quantitative PCR is the standard nucleic acid amplification test for CoV2, although reverse transcription loop-mediated isothermal amplification is used in diagnostics. The authors demonstrate a sequence-specific reverse transcription loop-mediated isothermal amplification-based nucleic acid amplification assay that is finished within 30 min using minimally processed clinical nasal swab samples and describe a fluorescence-quenched reverse transcription loop-mediated isothermal amplification assay using labeled primers and a quencher oligonucleotide. This assay can achieve rapid (30 min) and sensitive (1000 plaque-forming units/ml) fluorescence detection of CoV2 (WA1/2020), B.1.1.7 (Alpha) and variants of concern Delta (B.1.617.2) and Omicron (B.1.1.529) in nasal samples.
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- 2022
3. Data from Inhibition of Cholinergic Signaling Causes Apoptosis in Human Bronchioalveolar Carcinoma
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Piyali Dasgupta, Brandon S. Shiflett, Yi C. Chen, Haitao Luo, A. Betts Carpenter, Cody A. Stover, Christopher A. McNees, W. Elaine Hardman, Theodore R. Witte, Aaron M. Dom, Clayton M. Crabtree, Brent A. Thornhill, Kathleen C. Brown, and Jamie K. Lau
- Abstract
Recent case-controlled clinical studies show that bronchioalveolar carcinomas (BAC) are correlated with smoking. Nicotine, the addictive component of cigarettes, accelerates cell proliferation through nicotinic acetylcholine receptors (nAChR). In this study, we show that human BACs produce acetylcholine (ACh) and contain several cholinergic factors including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1, SLC5A7), vesicular acetylcholine transporter (VAChT, SLC18A3), and nACh receptors (AChRs, CHRNAs). Nicotine increased the production of ACh in human BACs, and ACh acts as a growth factor for these cells. Nicotine-induced ACh production was mediated by α7-, α3β2-, and β3-nAChRs, ChAT and VAChT pathways. We observed that nicotine upregulated ChAT and VAChT. Therefore, we conjectured that VAChT antagonists, such as vesamicol, may suppress the growth of human BACs. Vesamicol induced potent apoptosis of human BACs in cell culture and nude mice models. Vesamicol did not have any effect on EGF or insulin-like growth factor-II–induced growth of human BACs. siRNA-mediated attenuation of VAChT reversed the apoptotic activity of vesamicol. We also observed that vesamicol inhibited Akt phosphorylation during cell death and that overexpression of constitutively active Akt reversed the apoptotic activity of vesamicol. Taken together, our results suggested that disruption of nicotine-induced cholinergic signaling by agents such as vesamicol may have applications in BAC therapy. Cancer Res; 73(4); 1328–39. ©2012 AACR.
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- 2023
4. Supplementary Methods, Figures 1 - 8 from Inhibition of Cholinergic Signaling Causes Apoptosis in Human Bronchioalveolar Carcinoma
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Piyali Dasgupta, Brandon S. Shiflett, Yi C. Chen, Haitao Luo, A. Betts Carpenter, Cody A. Stover, Christopher A. McNees, W. Elaine Hardman, Theodore R. Witte, Aaron M. Dom, Clayton M. Crabtree, Brent A. Thornhill, Kathleen C. Brown, and Jamie K. Lau
- Abstract
PDF file - 490K, Figure S1: Cell line authentication data Figure S2: Full screen western blots for ChAT, VAChT, AChE and CHT1 Figure S3: Immunohistochemistry of ChAT and VAChT in normal human lung tissues Figure S4: Nicotine-induced ACh production in human BAC requires nAChRs, VAChT, and CHT1 Figure S5: VAChT and ChAT are expressed on human BACs Figure S6: Transfection of VAChT siRNA and Sigma-R siRNA suppress the expression of these proteins in human BACs Figure S7: Effect of VAChT siRNA on the apoptotic activity of vesamicol in nicotine-treated BACs Figure S8: Overexpression of pcDNA3-HA-Akt-CA in A549 and H358 human BAC cells
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- 2023
5. Phenethyl isothiocyanate inhibits <scp>CD133</scp> +/ <scp>CD90</scp> + liver cancer stem cells by modulation of <scp>microRNA</scp> ‐214‐β‐catenin epigenome axis
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Yi C. Chu, Sheng‐Tsai Lin, Syahru A. Setiawan, Ming‐Shou Hsieh, Vijesh K. Yadav, Ting‐Yi Huang, Chi‐Tai Yeh, and Ming‐Yao Chen
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General Medicine - Published
- 2023
6. Digital Holography for Investigating Front-Edge Instabilities of Liquid Jets in Supersonic Crossflows
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Joshua A. Johnson, Suresh Menon, and Yi C. Mazumdar
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- 2023
7. Analysis of Holography Techniques for Phase Distortion Removal in Extreme Environments
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Andrew W. Marsh, Zachary D'Ambra, Anthony McMaster, Daniel R. Guildenbecher, and Yi C. Mazumdar
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- 2023
8. Planar Time-Resolved Laser-Induced Incandescence for Particulate Emissions in Premixed Flames at Elevated Pressures
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Andy X. Zheng, Sundar Manikandan, Samuel E. Wonfor, Adam M. Steinberg, and Yi C. Mazumdar
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- 2023
9. Forced and Unforced Dynamics of a Lean Premixed Prevaporized Combustor for Civil Supersonic Transport
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Mitchell L. Passarelli, Samuel E. Wonfor, Andy X. Zheng, Yi C. Mazumdar, Jerry M. Seitzman, Adam M. Steinberg, Victor Salazar, Krishna Venkatesan, and Michael Benjamin
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- 2023
10. High Temperature Gladstone-Dale Coefficient Measurements in a Free-Piston Shock Tube
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Gwendolyn Wang, Kyle Daniel, Kyle P. Lynch, Daniel R. Guildenbecher, and Yi C. Mazumdar
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- 2023
11. Changes within the central stalk of E. coli F1Fo ATP synthase observed after addition of ATP
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Meghna Sobti, Yi C. Zeng, James L. Walshe, Simon H. J. Brown, Robert Ishmukhametov, and Alastair G. Stewart
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Medicine (miscellaneous) ,General Agricultural and Biological Sciences ,General Biochemistry, Genetics and Molecular Biology - Abstract
F1Fo ATP synthase functions as a biological generator and makes a major contribution to cellular energy production. Proton flow generates rotation in the Fo motor that is transferred to the F1 motor to catalyze ATP production, with flexible F1/Fo coupling required for efficient catalysis. F1Fo ATP synthase can also operate in reverse, hydrolyzing ATP and pumping protons, and in bacteria this function can be regulated by an inhibitory ε subunit. Here we present cryo-EM data showing E. coli F1Fo ATP synthase in different rotational and inhibited sub-states, observed following incubation with 10 mM MgATP. Our structures demonstrate how structural transitions within the inhibitory ε subunit induce torsional movement in the central stalk, thereby enabling its rotation within the Fο motor. This highlights the importance of the central rotor for flexible coupling of the F1 and Fo motors and provides further insight into the regulatory mechanism mediated by subunit ε.
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- 2023
12. Softening of a flat phonon mode in the kagome ScV$_6$Sn$_6$
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Korshunov, A., Hu, H., Subires, D., Jiang, Y., Călugăru, D., Feng, X., Rajapitamahuni, A., Yi, C., Roychowdhury, S., Vergniory, M. G., Strempfer, J., Shekhar, C., Vescovo, E., Chernyshov, D., Said, A. H., Bosak, A., Felser, C., Bernevig, B. Andrei, and Blanco-Canosa, S.
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Condensed Matter - Strongly Correlated Electrons ,Condensed Matter - Materials Science ,Condensed Matter - Mesoscale and Nanoscale Physics ,Strongly Correlated Electrons (cond-mat.str-el) ,Mesoscale and Nanoscale Physics (cond-mat.mes-hall) ,Materials Science (cond-mat.mtrl-sci) ,FOS: Physical sciences - Abstract
The long range electronic modulations recently discovered in the geometrically frustrated kagome lattice have opened new avenues to explore the effect of correlations in materials with topological electron flat bands. The observation of the lattice response to the emergent new phases of matter, a soft phonon mode, has remained elusive and the microscopic origin of charge density waves (CDWs) is still unknown. Here, we show, for the first time, a complete melting of the ScV$_ 6$Sn$_ 6$ (166) kagome lattice. The low energy phonon with propagation vector $\frac{1}{3} \frac{1}{3} \frac{1}{2}$ collapses at 98 K, without the emergence of long-range charge order, which sets in with a propagation vector $\frac{1}{3} \frac{1}{3} \frac{1}{3}$. The CDW is driven (but locks at a different vector) by the softening of an overdamped phonon flat plane at k$_z$=$\pi$. We observe broad phonon anomalies in momentum space, pointing to (1) the existence of approximately flat phonon bands which gain some dispersion due to electron renormalization, and (2) the effects of the momentum dependent electron-phonon interaction in the CDW formation. Ab initio and analytical calculations corroborate the experimental findings to indicate that the weak leading order phonon instability is located at the wave vector $\frac{1}{3} \frac{1}{3} \frac{1}{2}$ of a rather flat collapsed mode. We analytically compute the phonon frequency renormalization from high temperatures to the soft mode, and relate it to a peak in the orbital-resolved susceptibility, obtaining an excellent match with both ab initio and experimental results, and explaining the origin of the approximately flat phonon dispersion. Our data report the first example of the collapse of a softening of a flat phonon plane and promote the 166 compounds of the kagome family as primary candidates to explore correlated flat phonon-topological flat electron physics., Comment: 10 pages, 4 figures
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- 2023
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13. Minimum number-phase uncertainty states via weighted Bergman spaces
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Huang, Yi C.
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81Q10, 30H20 ,Mathematics - Complex Variables ,FOS: Mathematics ,Complex Variables (math.CV) - Abstract
The number-phase uncertainty result of Luo via the Hardy space on unit disc (Phys Lett A, 2000) is extended in this paper to the scale of weighted Bergman spaces. The minimum uncertainty states are thereby explicitly identified., Comment: a note written in the winter vacation of 2022-2023 and for fun
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- 2023
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14. Rellich Inequality via Radial Dissipativity
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Huang, Yi C.
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Mathematics - Classical Analysis and ODEs ,Classical Analysis and ODEs (math.CA) ,FOS: Mathematics ,Primary 26D10, Secondary 46E35, 35A23 - Abstract
We give a conceptually simple and essentially one-dimensional approach to Rellich inequality in Euclidean space $\mathbb{R}^n$. In particular, we show that the radial part and the spherical part of the standard Laplacian form an angle in $[0,\pi/2]$ when $n\geq4$, a property known in the works of Evans-Lewis, Machihara-Ozawa-Wadade, and Bez-Machihara-Ozawa. Our proof here is direct and short.
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- 2023
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15. Rellich type inequalities on the half line in the framework of equalities
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Huang, Yi C. and Shi, Fuping
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Mathematics - Functional Analysis ,Mathematics - Classical Analysis and ODEs ,Classical Analysis and ODEs (math.CA) ,FOS: Mathematics ,Functional Analysis (math.FA) - Abstract
We establish in this paper some weighted Hardy and Rellich type inequalities on the half line in the framework of equalities, extending recent results proved by Machihara-Ozawa-Wadade and Bez-Machihara-Ozawa. In particular, the one-dimensional classical Rellich inequality is proved in the framework of equality.
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- 2023
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16. On eigenvalue inequalities of Schmuckenschlager
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Huang, Yi C.
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Mathematics - Functional Analysis ,Mathematics - Classical Analysis and ODEs ,Classical Analysis and ODEs (math.CA) ,FOS: Mathematics ,Primary 35P15, Secondary 60J65 ,Functional Analysis (math.FA) - Abstract
About ten years ago, Schmuckenschl\"ager proved that the lowest eigenvalue of Dirichlet Laplacian for the intersection of two balls (i.e., convex, symmetric and compact subsets of $\mathbb{R}^n$ with non-empty interior) is less than the sum of the lowest eigenvalue for each. His arguments rely on Kac's formula, the log-concavity of Gaussian measures, the symmetry of balls and Lieb's classical result for the intersection of two domains. In this note we revisit Schmuckenschl\"ager's proof and propose a direct and elementary Lieb-free approach to these inequalities.
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- 2023
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17. On the bilinear estimate of Ozawa and Rogers for the one-dimensional Klein-Gordon equation and some related lower Jacobian estimates
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Chen, Shirong, Huang, Yi C., and Xu, Shaozhen
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Mathematics - Analysis of PDEs ,Mathematics - Classical Analysis and ODEs ,Classical Analysis and ODEs (math.CA) ,FOS: Mathematics ,Primary 35B45, Secondary 26D07, 42B05, 81Q05 ,Analysis of PDEs (math.AP) - Abstract
We give a natural convexity proof of an elementary inequality used by Ozawa and Rogers in proving their bilinear estimate for the one-dimensional Klein-Gordon equation. This robust approach also enables us to derive the optimality of Ozawa-Rogers estimate and establish a new bilinear estimate. Our estimate is in sharp analogy with the bilinear estimate of Bez and Rogers for the wave equation. We also present an alternative proof of some lower Jacobian estimates used crucially by Ozawa and Rogers in proving their Fourier restriction results on the whole hyperbola. Based on interpolation, our proof is purely non-trigonometric., Comment: added a section which presents an alternative non-trigonometric proof of some intriguing lower Jacobian estimates
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- 2023
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18. Change of variable and discrete Hardy inequality
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Huang, Yi C.
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Primary 40G05, 26D15 ,Mathematics - Classical Analysis and ODEs ,Classical Analysis and ODEs (math.CA) ,FOS: Mathematics - Abstract
For absolutely convergent series we state explicitly a one-sided summation estimate that can be viewed as the discrete analogue of the change of variable formula on the half line. This estimate is implicit in Pascal Lef\`evre's recent elegant proof of the classical discrete Hardy inequality. Here we remove a superfluous irrationality condition therein and point out the change of variable character of his approach. This leads to a simpler, shorter and \textit{bona fide} Ingham type proof of the discrete Hardy inequality, and also provides the optimal constant., Comment: This is a companion note of ''A first order proof of the improved discrete Hardy inequality. Arch. Math. 117, 671-674 (2021)'' and was written in 08/2021. In light of the supersolution language of Pinchover et al., our motivation is to unify, at least conceptually, the proofs for both the discrete and the continuous Hardy inequalities
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- 2023
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19. The forward maximal regularity operator commutes with the backward
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Huang, Yi C.
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Mathematics - Functional Analysis ,35K90 (Primary), 42A38, 47A60 (Secondary) ,FOS: Mathematics ,Functional Analysis (math.FA) - Abstract
Given a generator of a bounded analytic semigroup on a Hilbert space, we show that the corresponding forward maximal regularity operator commutes with the backward. In particular, for self-adjoint generators the images under the two maximal regularity operators have equal unweighted Hilbert space norms., Comment: fixed a typo: "apply Theorem 2.1 or solely (3.2)" to "apply Theorem 2.1 or solely (2.2)"
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- 2023
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20. Characterization of a 3D Printed Electric Solenoid with Multi-layer Silver Nanoparticle Traces
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Sebastian Mettes, Noah Kohls, Kenneth W. Allen, and Yi C. Mazumdar
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Control and Systems Engineering - Published
- 2022
21. О свойстве гиперсжатия полугруппы Пуассона для сфер высших размерностей
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Yi C. Huang
- Abstract
Рассмотрена модификация вопроса Мюллера и Вайслера, поставленного в 1982 г. Обобщен классический результат Бекнера относительно гипотезы Стейна, а также недавний результат Франка и Иванишвили. А именно, доказано, что для $1
- Published
- 2022
22. Determining the role of natural SARS-CoV-2 infection in the death of domestic pets: 10 cases (2020–2021)
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Dustin W. Currie, Jana M. Ritter, Mia Kim Torchetti, Brent Robbins, Deepanker Tewari, Francisco R. Carvallo, Sally Slavinski, Kelley Steury, Betsy Schroeder, Ryan M. Wallace, Dee Jones, Jane A. Rooney, Ria R. Ghai, James B. Stanton, Boyd Parr, Julia Murphy, Diego G. Diel, Casey Barton Behravesh, Carl Williams, Gary Balsamo, Hemant Naikare, Kevin Brightbill, Mathias Martins, Janemarie H. Hennebelle, Rachel Radcliffe, Joy Gary, Robert Cobb, Lore Boger, Tony Frazier, Natalie Wendling, Yung-Yi C. Mosley, Kathryn McCullough, Ann Carpenter, David J. Smith, Julie Gabel, and Doug Meckes
- Subjects
2019-20 coronavirus outbreak ,General Veterinary ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,business.industry ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,fungi ,COVID-19 ,Pets ,Cat Diseases ,Virology ,respiratory tract diseases ,body regions ,Dogs ,Cats ,Animals ,Medicine ,Dog Diseases ,skin and connective tissue diseases ,business - Abstract
OBJECTIVE To establish a pathoepidemiological model to evaluate the role of SARS-CoV-2 infection in the first 10 companion animals that died while infected with SARS-CoV-2 in the US. ANIMALS 10 cats and dogs that tested positive for SARS-CoV-2 and died or were euthanized in the US between March 2020 and January 2021. PROCEDURES A standardized algorithm was developed to direct case investigations, determine the necessity of certain diagnostic procedures, and evaluate the role, if any, that SARS-CoV-2 infection played in the animals’ course of disease and death. Using clinical and diagnostic information collected by state animal health officials, state public health veterinarians, and other state and local partners, this algorithm was applied to each animal case. RESULTS SARS-CoV-2 was an incidental finding in 8 animals, was suspected to have contributed to the severity of clinical signs leading to euthanasia in 1 dog, and was the primary reason for death for 1 cat. CONCLUSIONS AND CLINICAL RELEVANCE This report provides the global community with a standardized process for directing case investigations, determining the necessity of certain diagnostic procedures, and determining the clinical significance of SARS-CoV-2 infections in animals with fatal outcomes and provides evidence that SARS-CoV-2 can, in rare circumstances, cause or contribute to death in pets.
- Published
- 2021
23. Characterizing the CH3SSCH3–Au(111) System From Single Molecules To Full Surface Coverage: A Scanning Tunneling Microscopy Study
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Yi C. Zhang, David Y. Lee, and K. W. Hipps
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Surface (mathematics) ,Materials science ,Resolution (electron density) ,Analytical chemistry ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,law.invention ,chemistry.chemical_compound ,General Energy ,Two temperature ,Adsorption ,chemistry ,law ,Molecule ,Dimethyl disulfide ,Physical and Theoretical Chemistry ,Scanning tunneling microscope - Abstract
The adsorption process of dimethyl disulfide onto the Au(111) surface was resolved with subnanometer resolution at temperatures below 130 K. We report two temperature dependent adsorption studies t...
- Published
- 2021
24. Rapid Detection of SARS-CoV-2 RNA in Human Nasopharyngeal Specimens Using Surface-Enhanced Raman Spectroscopy and Deep Learning Algorithms
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Yanjun Yang, Hao Li, Les Jones, Jackelyn Murray, James Haverstick, Hemant K. Naikare, Yung-Yi C. Mosley, Ralph A. Tripp, Bin Ai, and Yiping Zhao
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Fluid Flow and Transfer Processes ,Process Chemistry and Technology ,Bioengineering ,Instrumentation - Abstract
A rapid and cost-effective method to detect the infection of SARS-CoV-2 is fundamental to mitigating the current COVID-19 pandemic. Herein, a surface-enhanced Raman spectroscopy (SERS) sensor with a deep learning algorithm has been developed for the rapid detection of SARS-CoV-2 RNA in human nasopharyngeal swab (HNS) specimens. The SERS sensor was prepared using a silver nanorod array (AgNR) substrate by assembling DNA probes to capture SARS-CoV-2 RNA. The SERS spectra of HNS specimens were collected after RNA hybridization, and the corresponding SERS peaks were identified. The RNA detection range was determined to be 10
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- 2022
25. Lipid-Nanoparticle-Mediated Delivery of Docetaxel Prodrug for Exploiting Full Potential of Gold Nanoparticles in the Treatment of Pancreatic Cancer
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Abdulaziz Alhussan, Nolan Jackson, Sarah Eaton, Nancy Dos Santos, Ingrid Barta, Josh Zaifman, Sam Chen, Yuen Yi C. Tam, Sunil Krishnan, and Devika B. Chithrani
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Cancer Research ,gold nanoparticles ,docetaxel ,lipid nanoparticles ,pancreatic cancer ,nanomedicine ,Oncology - Abstract
Current chemoradiation therapy suffers from normal tissue toxicity. Thus, we are proposing incorporating gold nanoparticles (GNPs) and docetaxel (DTX), as they have shown very promising synergetic radiosensitization effects. Here, we explored the effect of a DTX prodrug encapsulated in lipid nanoparticles (LNPDTX-P) on GNP uptake in pancreatic cancer models in vitro and in vivo. For the in vitro experiment, a pancreatic cancer cell line, MIA PaCa-2, was cultured and dosed with 1 nM GNPs and 45 nM free DTX or an equivalent dose of LNPDTX-P. For the in vivo experiment, MIA PaCa-2 cells were implanted subcutaneously in NRG mice, and the mice were dosed with 2 mg/kg of GNPs and 6 mg/kg of DTX or an equivalent dose of LNPDTX-P. The results show that LNPDTX-P-treated tumour samples had double the amount GNPs compared to control samples, both in vitro and in vivo. The results are very promising, as LNPDTX-P have superior targeting of tumour tissues compared to free DTX due to their nanosize and their ability to be functionalized. Because of their minimal toxicity to normal tissues, both GNPs and LNPDTX-P could be ideal radiosensitization candidates in radiotherapy and would produce very promising synergistic therapeutic outcomes.
- Published
- 2022
26. Lipid Nanoparticle Mediated Delivery of Docetaxel Prodrug for Exploiting Full Potential of Gold Radiosensitizers in the Treatment of Pancreatic Cancer
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Abdulaziz Alhussan, Nolan Jackson, Sarah Eaton, Nancy Dos Santos, Ingrid Barta, Josh Zaifman, Sam Chen, Yuen Yi C. Tam, Sunil Krishnan, and Devika B. Chithrani
- Abstract
Background Pancreatic cancer is one of the leading causes of cancer deaths worldwide. Current chemoradiation therapy suffers from normal tissue toxicity. To overcome this problem, we are proposing incorporating nanoparticles as radiosensitizers and as drug delivery vehicles into current chemoradiation regimes. Gold nanoparticles (GNPs) and Docetaxel (DTX) have shown very promising synergetic radiosensitization effects despite DTX toxicity to normal tissues. Here, we explored the effect of DTX prodrug encapsulated in lipid nanoparticles (LNPDTX−P) on GNP uptake in pancreatic cancer models in vitro and in vivo. Methods For the in vitro experiment, pancreatic cancer cell line, MIA PaCa-2, were cultured and dosed with 7.5 µg/mL of GNPs (of ~ 11 nm in diameter functionalized with PEG and RGD peptide) and with 45 nM of free DTX or equivalent dose of LNPDTX−P. For the in vivo experiment, MIA PaCa-2 were implanted subcutaneously in NRG mice and the mice were dosed with 2 mg/kg of GNPs and 6 mg/kg of DTX or equivalent dose of LNPDTX−P. GNPs content in mice and in cells were measured using Inductively Coupled Plasma–Mass Spectrometry (ICP–MS). Results The results show that LNPDTX−P treated tumour samples have no less than 191% increase in GNPs uptake compared to control samples in both in vitro and in vivo. The results also show that LNPDTX−P treated tumour samples have retained over 160% of GNPs compared to control samples in both in vitro and in vivo. No significant difference was found in GNP uptake or retention between free DTX and LNPDTX−P in tumour treated samples in vivo. Conclusions The results are very promising as LNPDTX−P have superior targeting of tumour tissues compared to free DTX due to their nano size and their ability to be functionalized. Because of their minimal toxicity to normal tissues, both GNPs and LNPDTX−P can be ideal radiosensitization candidates in radiotherapy and would produce very promising synergistic therapeutic outcome. Current radiotherapy treatments can hugely benefit from the effects of these two radiosensitizers boosting the radiation dose to the tumour while reducing the normal tissue dose. This in return will improve patient outcome and quality of life.
- Published
- 2022
27. The impact of COVID-19 on the mental health of pregnant women in Shanghai, China
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Yi, C., Tang, W., Xu, L., Yuan, H., and Zhang, J.
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China ,Mental Health ,Pregnancy ,SARS-CoV-2 ,Depression ,Public Health, Environmental and Occupational Health ,Humans ,COVID-19 ,Female ,Pregnant Women - Abstract
BackgroundCOVID-19 has dramatically impacted people's health, especially mental health. This study aimed to compare the psychological status of pregnant women before and after the COVID-19 outbreak.MethodsParticipants were recruited (from September 29, 2019, to November 5, 2020) and screened by the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale (GAD-7). The study participants were categorized into three groups based on two turning-points: January 23, 2020, when China initiated a locked-down strategy, and May 11, 2020, when Shanghai started to ease the COVID-19 measures. Multivariable logistic regression was used to determine the factors associated with depression and anxiety in pregnant women. We used enter method for variable selection; only variables with P ResultsWe recruited 478 pregnant women. After the outbreak, the depression rate (PHQ-9 ≥ 5) increased by 12.3% (from 35.4 to 47.7%), and the anxiety rate (GAD-7 ≥ 5) was stable (13.3 vs. 16.2%). The multivariable logistic regression results further confirmed that the odds of depression in pregnant women increased 81% after the outbreak (aOR = 1.81, 95%CI: 1.16–2.84). However, the median depression scale score was still statistically higher after the pandemic situation was stable (5.0 vs. 4.0) compared to the outbreak period.ConclusionThe depression rate increased among pregnant women after the outbreak and was not recovered after the ease of COVID-19 measures in Shanghai. Health institutes should pay attention to the long-term influence of the pandemic.
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- 2022
28. A first order proof of the improved discrete Hardy inequality
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Yi C. Huang
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Algebra ,Inequality ,General Mathematics ,media_common.quotation_subject ,First order ,Quantitative Biology::Cell Behavior ,Mathematics ,media_common - Abstract
We give an alternative first order proof of the improved discrete Hardy inequality recently found by Keller, Pinchover, and Pogorzelski.
- Published
- 2021
29. Synthesis and Characterization of Hybrid Lipid Nanoparticles Containing Gold Nanoparticles and a Weak Base Drug
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Igor V. Zhigaltsev, Yuen Yi C. Tam, Jayesh A. Kulkarni, and Pieter R. Cullis
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Doxorubicin ,Liposomes ,Electrochemistry ,Metal Nanoparticles ,Nanoparticles ,General Materials Science ,Surfaces and Interfaces ,Gold ,Condensed Matter Physics ,Spectroscopy - Abstract
Hybrid lipid nanoparticles containing gold nanoparticles (LNP-GNPs) and drugs have potential for imaging applications as well as triggered release of LNP contents in response to pulsed laser or X-ray radiation mediated by the GNPs. However, methods to synthesize LNP-GNP systems that efficiently entrap GNPs (the potential triggered release and imaging agent) and then load and retain the drug cargo in a manner that may have clinical applications have proven elusive. Here, we develop a straightforward "bottom-up" approach to manufacture drug-loaded LNP-GNP systems. We show that negatively charged GNPs of 5 nm diameter can be stably loaded into LNPs containing 10 mol % ionizable cationic lipid using an ethanol dilution, rapid mixing approach and that these systems also exhibit aqueous compartments. Further, we show that such systems can also entrap ammonium sulfate, enabling pH-dependent loading of the weak base anti-cancer drug doxorubicin into the aqueous compartments. Cryo-transmission electron microscopy (Cryo-TEM) imaging clearly demonstrates the presence of GNPs in the interior of the resulting hybrid nanostructures as well as the formation of electron-dense drug precipitates in the aqueous core of the LNP-GNPs. The approach described here is a robust and straightforward method to generate hybrid LNP-GNP-drug and other LNP-metal nanoparticle-drug systems with potential applications for a variety of triggered release protocols.
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- 2022
30. FQ-LAMP Assay for Detection of CoV2 in Clinical Nasal Swabs v1
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Les Jones, Hemant K. Naikare, Yung-Yi C. Mosley, and and Ralph A. Tripp
- Abstract
COVID-19 is a public health challenge requiring rapid testing for detecting infections and transmission. Nucleic acid amplification tests (NAAT) targeting SARS-CoV-2 (CoV2) are used to detect CoV2 in clinical samples.Real-time reverse transcription-quantitative PCR (RT-qPCR) is the standard NAAT for CoV2, although Reverse Transcription Loop-mediated isothermal amplification (RT-LAMP) is used in diagnostics. We show a sequence-specific RT-LAMP-based NAAT assay that is finished within 30 min using minimally processed clinical nasal swab samples and describe a fluorescent-quenched RT-LAMP assay (FQ-LAMP) using labeled primers and a quencher oligo. This assay can achieve rapid (30 min) and sensitive (1000 PFU/ml) fluorescent detection of CoV2 (WA1/2020), B.1.1.7 (Alpha), and variants of concern Delta (B.1.617.2) and Omicron (B.1.1.529) in nasal samples.
- Published
- 2022
31. On optimal bound of Foschi’s quadratic functional in higher-dimensional spheres
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Yi C. Huang and Shirong Chen
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symbols.namesake ,Pure mathematics ,Fourier transform ,Applied Mathematics ,010102 general mathematics ,0103 physical sciences ,symbols ,SPHERES ,010307 mathematical physics ,0101 mathematics ,01 natural sciences ,Quadratic functional ,Mathematics - Abstract
In proving his theorem on global maximizers for the sphere adjoint Fourier restriction inequality, D. Foschi studied some quadratic functional and determined its optimal bound. In this note we extend to higher-dimensional spheres his results on this quadratic functional.
- Published
- 2021
32. Effective and Safe Stimulation of Humoral and Cell-Mediated Immunity by Intradermal Immunization with a Cyclic Dinucleotide/Nanoparticle Combination Adjuvant
- Author
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Jackeline Franco, Yung-Yi C. Mosley, Juan F Hernandez-Franco, Harm HogenEsch, Darryl Ragland, and Yuan Yao
- Subjects
Injections, Intradermal ,Swine ,medicine.medical_treatment ,Immunology ,Population ,Spleen ,Mice ,Immune system ,Adjuvants, Immunologic ,Cyclic AMP ,medicine ,Animals ,Humans ,Immunology and Allergy ,education ,Lymph node ,Cells, Cultured ,Immunity, Cellular ,Mice, Inbred BALB C ,education.field_of_study ,business.industry ,NF-kappa B ,Germinal center ,Dendritic Cells ,Dendritic cell ,Plants ,Th1 Cells ,Immunity, Humoral ,medicine.anatomical_structure ,Immunization ,Nanoparticles ,Female ,Inflammation Mediators ,business ,Adjuvant ,Signal Transduction - Abstract
Intradermal (ID) immunization is an attractive route of vaccination because it targets tissue rich in dendritic cells, has dose-sparing potential, and allows needle-free delivery. However, few adjuvants are effective, nonreactogenic, and compatible with needle-free delivery devices. In this study, we demonstrate that a combination adjuvant composed of cyclic-di-AMP (cdAMP) and the plant-derived nanoparticle adjuvant Nano-11 significantly enhanced the immune response to ID-injected vaccines in mice and pigs with minimal local reaction at the injection site. The cdAMP/Nano-11 combination adjuvant increased Ag uptake by lymph node–resident and migratory skin dendritic cell subpopulations, including Langerhans cells. ID immunization with cdAMP/Nano-11 expanded the population of germinal center B cells and follicular helper T cells in the draining lymph node and Ag-specific Th1 and Th17 cells in the spleen. It elicited an enhanced immune response with a significant increase of IgG1 and IgG2a responses in mice at a reduced dose compared with i.m. immunization. An increased IgG response was observed following needle-free ID immunization of pigs. Nano-11 and cdAMP demonstrated a strong synergistic interaction, as shown in the activation of mouse, human, and porcine APC, with increased expression of costimulatory molecules and secretion of TNF and IL-1β. The combination adjuvant induced robust activation of both NF-κB and IFN regulatory factor signaling pathways and the NLRP3 inflammasome. We conclude that the combination of Nano-11 and cdAMP is a promising adjuvant for ID delivery of vaccines that supports a balanced immune response.
- Published
- 2021
33. Transient electrophoresis in a suspension of charged particles with arbitrary electric double layers
- Author
-
Huan J. Keh and Yi C. Lai
- Subjects
Electrophoresis ,Materials science ,Clinical Biochemistry ,02 engineering and technology ,01 natural sciences ,Biochemistry ,Molecular physics ,Analytical Chemistry ,symbols.namesake ,Electricity ,Suspensions ,Zeta potential ,Colloids ,Debye length ,Ions ,010401 analytical chemistry ,Relaxation (NMR) ,Charge density ,021001 nanoscience & nanotechnology ,Charged particle ,0104 chemical sciences ,Condensed Matter::Soft Condensed Matter ,Volume fraction ,symbols ,Particle ,0210 nano-technology - Abstract
The startup of electrophoretic motion in a suspension of spherical colloidal particles, which may be charged with constant zeta potential or constant surface charge density, due to the sudden application of an electric field is analytically examined. The unsteady modified Stokes equation governing the fluid velocity field is solved with unit cell models. Explicit formulas for the transient electrophoretic velocity of the particle in a cell in the Laplace transforms are obtained as functions of relevant parameters. The transient electrophoretic mobility is a monotonic decreasing function of the particle-to-fluid density ratio and in general a decreasing function of the particle volume fraction, but it increases and decreases with a raise in the ratio of the particle radius to the Debye length for the particles with constant zeta potential and constant surface charge density, respectively. On the other hand, the relaxation time in the growth of the electrophoretic mobility increases substantially with an increase in the particle-to-fluid density ratio and with a decrease in the particle volume fraction but is not a sensitive function of the ratio of the particle radius to the Debye length. For specified values of the particle volume fraction and particle-to-fluid density ratio in a suspension, the relaxation times in the growth of the particle mobility in transient electrophoresis and transient sedimentation are equivalent.
- Published
- 2021
34. Lipid nanoparticles to silence androgen receptor variants for prostate cancer therapy
- Author
-
Joslyn Quick, Nancy Dos Santos, Miffy H.Y. Cheng, Nisha Chander, Cedric A. Brimacombe, Jayesh Kulkarni, Roy van der Meel, Yuen Yi C. Tam, Dominik Witzigmann, Pieter R. Cullis, Precision Medicine, and ICMS Core
- Subjects
Male ,Prostate cancer ,Pharmaceutical Science ,Lipid nanoparticle ,Prostatic Neoplasms ,Androgen Antagonists ,Prostate-Specific Antigen ,SDG 3 – Goede gezondheid en welzijn ,Ligands ,Androgen receptor ,Mice ,Gene therapy ,SDG 3 - Good Health and Well-being ,Receptors, Androgen ,siRNA ,Cell Line, Tumor ,Liposomes ,Androgens ,Animals ,Humans ,Nanoparticles ,Tissue Distribution ,RNA, Messenger ,RNA, Small Interfering ,Splice variant - Abstract
Advanced-stage prostate cancer remains an incurable disease with poor patient prognosis. There is an unmet clinical need to target androgen receptor (AR) splice variants, which are key drivers of the disease. Some AR splice variants are insensitive to conventional hormonal or androgen deprivation therapy due to loss of the androgen ligand binding domain at the C-terminus and are constitutively active. Here we explore the use of RNA interference (RNAi) to target a universally conserved region of all AR splice variants for cleavage and degradation, thereby eliminating protein level resistance mechanisms. To this end, we tested five siRNA sequences designed against exon 1 of the AR mRNA and identified several that induced potent knockdown of full-length and truncated variant ARs in the 22Rv1 human prostate cancer cell line. We then demonstrated that 2′O methyl modification of the top candidate siRNA (siARvm) enhanced AR and AR-V7 mRNA silencing potency in both 22Rv1 and LNCaP cells, which represent two different prostate cancer models. For downstream in vivo delivery, we formulated siARvm-LNPs and functionally validated these in vitro by demonstrating knockdown of AR and AR-V7 mRNA in prostate cancer cells and loss of AR-mediated transcriptional activation of the PSA gene in both cell lines following treatment. We also observed that siARvm-LNP induced cell viability inhibition was more potent compared to LNP containing siRNA targeting full-length AR mRNA (siARfl-LNP) in 22Rv1 cells as their proliferation is more dependent on AR splice variants than LNCaP and PC3 cells. The in vivo biodistribution of siARvm-LNPs was determined in 22Rv1 tumor-bearing mice by incorporating 14C-radiolabelled DSPC in LNP formulation, and we observed a 4.4% ID/g tumor accumulation following intravenous administration. Finally, treatment of 22Rv1 tumor bearing mice with siARvm-LNP resulted in significant tumor growth inhibition and survival benefit compared to siARfl-LNP or the siLUC-LNP control. To best of our knowledge, this is the first report demonstrating therapeutic effects of LNP-siRNA targeting AR splice variants in prostate cancer.
- Published
- 2022
35. Exosomes as Targeted Delivery Drug System: Advances in Exosome Loading, Surface Functionalization and Potential for Clinical Application
- Author
-
Zun Y. Guo, Yue Tang, and Yi C. Cheng
- Subjects
Pharmaceutical Science - Abstract
Abstract: Exosomes are subtypes of vesicles secreted by almost all cells and can play an important role in intercellular communication. They contain various proteins, lipids, nucleic acids and other natural substances from their metrocytes. Exosomes are expected to be a new generation of drug delivery system due to their low immunogenicity, high potential to transfer bioactive substances and biocompatibility. However, exosomes themselves are not highly targeted, it is necessary to develop new surface modification techniques and targeted drug delivery strategies, which are the focus of drug delivery research. In this review, we introduced the biogenesis of exosomes and their role of intercellular communication. We listed various advanced exosome drug loading techniques. Emphatically, we summarized different exosome surface modification techniques and targeted drug delivery strategies. In addition, we discussed the application of exosomes in vaccine and briefly introduced milk exosomes. Finally, we clarified the clinical application prospects and shortcomings of exosomes.
- Published
- 2022
36. Experimental Characterization of a Lean Prevaporized Premixed Combustor for Supersonic Transport Applications
- Author
-
Mitchell L. Passarelli, Samuel E. Wonfor, Andy X. Zheng, Sundar Ram Manikandan, Yi C. Mazumdar, Jerry M. Seitzman, Adam M. Steinberg, Hannah Bower, John Hong, Krishna Venkatesan, and Michael Benjamin
- Published
- 2022
37. Transient electrophoresis of a charged porous particle
- Author
-
Yi C. Lai and Huan J. Keh
- Subjects
Electrophoresis ,Materials science ,Clinical Biochemistry ,02 engineering and technology ,Electrolyte ,01 natural sciences ,Biochemistry ,Permeability ,Analytical Chemistry ,Physics::Fluid Dynamics ,symbols.namesake ,Electric field ,Porosity ,Debye ,Condensed matter physics ,Viscosity ,010401 analytical chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Flow velocity ,Permeability (electromagnetism) ,symbols ,0210 nano-technology ,Dimensionless quantity - Abstract
The starting electrophoretic motion of a porous, uniformly charged, spherical particle, which models a solvent-permeable and ion-penetrable polyelectrolyte coil or floc of nanoparticles, in an arbitrary electrolyte solution due to the sudden application of an electric field is studied for the first time. The unsteady Stokes/Brinkman equations with the electric force term governing the fluid velocity fields are solved by means of the Laplace transform. An analytical formula for the electrophoretic mobility of the porous sphere is obtained as a function of the dimensionless parameters κ a , λ a , ρ p / ρ , and ν t / a 2 , where a is the radius of the particle, κ is the Debye screening parameter, λ is the reciprocal of the square root of the fluid permeability in the particle, ρp and ρ are the mass densities of the particle and fluid, respectively, ν is the kinematic viscosity of the fluid, and t is the time. The electrophoretic mobility normalized by its steady-state value increases monotonically with increases in ν t / a 2 and κ a , but decreases monotonically with an increase in ρ p / ρ , keeping the other parameters unchanged. In general, a porous particle with a high fluid permeability trails behind an identical porous particle with a lower permeability and a corresponding hard particle in the growth of the normalized electrophoretic mobility The normalized electrophoretic acceleration of the porous sphere decreases monotonically with an increase in the time and increases with an increase in λ a from zero at λ a = 0 .
- Published
- 2020
38. Spontaneous, solvent-free entrapment of siRNA within lipid nanoparticles
- Author
-
Sarah B. Thomson, Josh Zaifman, Blair R. Leavitt, Terri L. Petkau, Jayesh A. Kulkarni, Pieter R. Cullis, Austin Hill, Jerry Leung, Yuen Yi C. Tam, and Pamela K. Wagner
- Subjects
Nanoparticle ,02 engineering and technology ,Polyethylene glycol ,Cell Line ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Dynamic light scattering ,Lab-On-A-Chip Devices ,Phosphatidylcholine ,PEG ratio ,Animals ,General Materials Science ,RNA, Small Interfering ,Dissolution ,030304 developmental biology ,0303 health sciences ,SARS-CoV-2 ,Vesicle ,COVID-19 ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,Lipids ,chemistry ,Nucleic acid ,Biophysics ,Nanoparticles ,0210 nano-technology - Abstract
Lipid nanoparticle (LNP) formulations of nucleic acid are leading vaccine candidates for COVID-19, and enabled the first approved RNAi therapeutic, Onpattro. LNPs are composed of ionizable cationic lipids, phosphatidylcholine, cholesterol, and polyethylene glycol (PEG)-lipids, and are produced using rapid-mixing techniques. These procedures involve dissolution of the lipid components in an organic phase and the nucleic acid in an acidic aqueous buffer (pH 4). These solutions are then combined using a continuous mixing device such as a T-mixer or microfluidic device. In this mixing step, particle formation and nucleic acid entrapment occur. Previous work from our group has shown that, in the absence of nucleic acid, the particles formed at pH 4 are vesicular in structure, a portion of these particles are converted to electron-dense structures in the presence of nucleic acid, and the proportion of electron-dense structures increases with nucleic acid content. What remained unclear from previous work was the mechanism by which vesicles form electron-dense structures. In this study, we use cryogenic transmission electron microscopy and dynamic light scattering to show that efficient siRNA entrapment occurs in the absence of ethanol (contrary to the established paradigm), and suggest that nucleic acid entrapment occurs through inversion of preformed vesicles. We also leverage this phenomenon to show that specialized mixers are not required for siRNA entrapment, and that preformed particles at pH 4 can be used for in vitro transfection.
- Published
- 2020
39. Successful Management of Paroxysmal Sympathetic Hyperactivity in Anti-N-Methyl-D-Aspartate Receptor Encephalitis
- Author
-
Jing C and Yi C
- Subjects
business.industry ,Medicine ,Pharmacology ,business ,Paroxysmal sympathetic hyperactivity ,medicine.disease ,Anti-N-Methyl-D-Aspartate Receptor Encephalitis - Published
- 2019
40. Highly Selective Photocatalytic Valorization of Lignin Model Compounds Using Ultrathin Metal/CdS
- Author
-
Guanqun Han, Tao Yan, Yi C. Zhang, Wei Zhang, David Y. Lee, Zhi Cao, and Yujie Sun
- Subjects
010405 organic chemistry ,Chemistry ,Depolymerization ,food and beverages ,Biomass ,General Chemistry ,010402 general chemistry ,Highly selective ,complex mixtures ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Organic molecules ,Metal ,chemistry.chemical_compound ,Chemical engineering ,visual_art ,Photocatalysis ,visual_art.visual_art_medium ,Lignin - Abstract
Depolymerization of recalcitrant lignin is a crucial step in realizing the full potential of transforming biomass to value-added small organic molecules. Herein, we report a photocatalytic system c...
- Published
- 2019
41. Shock Tube Index of Refraction Measurements using a Quadrature Fringe Imaging Interferometer
- Author
-
Gwendolyn Wang, Yuzhe Peng, Wenting Sun, and Yi C. Mazumdar
- Published
- 2021
42. A consequence of complementary symmetry
- Author
-
Qingyun Gui and Yi C. Huang
- Subjects
Applied Mathematics ,General Psychology - Published
- 2022
43. Hybrid interferometric diagnostic for the refractive index measurement across nearly discrete shock waves
- Author
-
Gwendolyn T. Wang, Yuzhe Peng, Daniel R. Guildenbecher, Kyle P. Lynch, Wenting Sun, and Yi C. Mazumdar
- Subjects
Atomic and Molecular Physics, and Optics - Abstract
The measurement of high temperature gas properties is key for characterizing high speed flows. Nearly discrete changes in density across shock waves, in particular, are difficult to resolve through traditional fringe-counting interferometric methods. Existing techniques for estimating large fringe jumps are either resolution limited or require specialized window configurations. In this Letter, we describe a unique hybrid interferometric technique that combines narrowband fringes for high resolution and broadband fringes as an absolute reference to measure changes in refractive index with a resolution of up to 7 × 10−8 across nearly discrete index changes of up to 1.5 × 10−4. By capturing fringes with an ultrahigh-speed camera, the refractive index changes across discrete shock fronts can be estimated inside a shock tube with high accuracy and time resolution. First, a novel hybrid calibration method for tracking finite fringes is discussed. Next, this technique is used to measure the post-initial-shock refractive indices for Mach 2.7 to 4.2 flows (pressures from 90.4 to 228.4 kPa). Results are then compared with theoretical values showing agreement within 2%.
- Published
- 2022
44. Scalable Production of Lipid Nanoparticles Containing Amphotericin B
- Author
-
Jayesh A. Kulkarni, Sam Chen, and Yuen Yi C. Tam
- Subjects
Nanoparticle ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,chemistry.chemical_compound ,Amphotericin B ,Electrochemistry ,medicine ,General Materials Science ,Solubility ,RNA, Small Interfering ,IC50 ,Spectroscopy ,Liposome ,Chemistry ,Dimethyl sulfoxide ,Surfaces and Interfaces ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Small molecule ,Combinatorial chemistry ,Lipids ,0104 chemical sciences ,Solvent ,Nanoparticles ,0210 nano-technology ,medicine.drug - Abstract
Lipid-based formulations have been developed to improve stability profiles, tolerability, and toxicity profiles of small molecule drugs. However, manufacture of such formulations involving lipophilic compounds can be labor-intensive and difficult to scale because of solubility and solvent compatibility issues. We have developed a rapid and scalable approach using rapid-mixing techniques to generate homogeneous lipid nanoparticle (LNP) formulations of siRNA, triglycerides, and hydrophilic weak-base drugs. Here, we used this approach to entrap a hydrophobic small molecule, Amphotericin B (AmpB), a hydrophobic drug not soluble in ethanol. The three prototypes presented in this study were derived from LNP-siRNA systems, triglyceride nanoparticles, and liposomal systems. Cryogenic transmission electron microscopy (cryo-TEM) revealed that all three LNP-AmpB formulations retain structural characteristics of the parent (AmpB-free) LNPs, with particles remaining stable for at least 1 month. All formulations showed similar in vitro toxicity profiles in comparison to AmBisome. Importantly, the formulations have a 2.5-fold improved IC50 for fungal growth inhibition as compared to AmBisome in in vitro efficacy studies. These results demonstrate that the rapid-mixing technology combined with dimethyl sulfoxide (DMSO) for drugs insoluble in other organic solvents can be a powerful manufacturing method for the generation of stable LNP drug formulations.
- Published
- 2021
45. Determining the Role of Natural SARS-CoV-2 Infection in the Death of Ten Domestic Pets
- Author
-
Jana M. Ritter, Boyd Parr, Robert Cobb, Brent Robbins, Ann Carpenter, Gary Balsamo, Deepanker Tewari, Kelley Steury, Doug Meckes, James B. Stanton, Mathias Martins, Kevin Brightbill, Casey Barton Behravesh, Dee Jones, Joy Gary, Francisco R. Carvallo, David W. Smith, Julia Murphy, Carl Williams, Tony Frazier, Sally Slavinski, Natalie Wendling, Julie Gabel, Mia L. Torchetti, Kathryn McCullough, Hemant Naikare, Jane Rooney, Yung-Yi C. Mosley, Diego D. Diel, Betsy Schroeder, Ryan M. Wallace, Janemarie H. Hennebelle, Rachel Radcliff, Ria R. Ghai, Lore Boger, and Dustin W. Currie
- Subjects
body regions ,business.industry ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,fungi ,Medicine ,skin and connective tissue diseases ,business ,Virology ,respiratory tract diseases - Abstract
Transmission of SARS-CoV-2, the virus that causes COVID-19, from people to companion animals has been reported globally. Between March 2020 and January 2021, the United States reported 94 companion animals with SARS-CoV-2. While most animals with SARS-CoV-2 have mild illness, 10 animals (5 dogs, 5 cats) died around the time of SARS-CoV-2 diagnosis. In one dog, histopathologic changes suggest SARS-CoV-2 exacerbated a severe chronic respiratory disease and contributed to death. In one cat, SARS-CoV-2 was associated with histopathologic changes suggesting the virus caused clinical signs that resulted in euthanasia. In the remaining eight animals, SARS-CoV-2 infection was an incidental finding (4 dogs, 4 cats). This report provides evidence that in rare circumstances, SARS-CoV-2 can contribute to or cause death in companion animals with underlying conditions.
- Published
- 2021
46. Formulation of aluminum hydroxide adjuvant with TLR agonists poly(I:C) and CpG enhances the magnitude and avidity of the humoral immune response
- Author
-
Brooke E. Carmichael, Fangjia Lu, Harm HogenEsch, Yung Yi C. Mosley, and Devonte D. Brown
- Subjects
Agonist ,medicine.drug_class ,medicine.medical_treatment ,030231 tropical medicine ,Antibody Affinity ,Aluminum Hydroxide ,chemical and pharmacologic phenomena ,Pharmacology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Adjuvants, Immunologic ,medicine ,Animals ,Avidity ,030212 general & internal medicine ,Antigens ,General Veterinary ,General Immunology and Microbiology ,Chemistry ,Monocyte ,Toll-Like Receptors ,Public Health, Environmental and Occupational Health ,TLR9 ,Dendritic Cells ,Immunity, Humoral ,Poly I-C ,Infectious Diseases ,medicine.anatomical_structure ,Oligodeoxyribonucleotides ,Immunoglobulin G ,TLR3 ,Cytokines ,Molecular Medicine ,Female ,Tumor necrosis factor alpha ,Adjuvant - Abstract
Subunit vaccines generally require adjuvants to achieve optimal immune responses. Toll-like receptor (TLR) agonists are promising immune potentiators, but rapid diffusion from the injection site reduces their local effective concentration and may cause systemic reactions. In this study, we investigated the potential of aluminum hydroxide adjuvant (AH) to adsorb the TLR3 agonist poly(I:C) and TLR9 agonist CpG and compared the effect of the combination adjuvant on the immune response with either the TLR agonists or AH alone in mice. Poly(I:C) and CpG readily adsorbed onto AH and this combination adjuvant induced a stronger IgG1 and IgG2a immune response with a significant increase of antibody avidity. The combination adjuvant enhanced antigen uptake and activation of dendritic cells in vitro. It induced an inflammatory response at the injection site similar to AH but without eosinophils which are typically observed with AH. A distinctive antigen-containing monocyte/macrophage population with an intermediate level of CD11c expression was identified in the draining lymph nodes after immunization with TLR agonists and the combination adjuvant. Injection of the combination adjuvant did not induce an increase of TNFα and CXCL10 in serum in contrast to the injection of soluble TLR agonists. These results indicate that this combination adjuvant is a promising formulation to solve some of the unmet needs of current vaccines.
- Published
- 2019
47. Fusion-dependent formation of lipid nanoparticles containing macromolecular payloads
- Author
-
Roy van der Meel, Dominik Witzigmann, Jerry Leung, Hiu Man Grisch-Chan, Yuen Yi C. Tam, Pieter R. Cullis, Jayesh A. Kulkarni, Maria M. Darjuan, Josh Zaifman, Beat Thöny, University of Zurich, Kulkarni, Jayesh A, and Precision Medicine
- Subjects
Macromolecular Substances ,Phospholipid ,Nanoparticle ,Macromolecular Substances/chemistry ,610 Medicine & health ,Lipids/chemistry ,02 engineering and technology ,Polyethylene glycol ,010402 general chemistry ,01 natural sciences ,Polyethylene Glycols ,chemistry.chemical_compound ,PEG ratio ,Messenger/chemistry ,General Materials Science ,Genetic Therapy/methods ,RNA, Messenger ,Particle Size ,RNA, Small Interfering ,Liposome ,Aqueous solution ,RNA, Small Interfering/chemistry ,Cryoelectron Microscopy ,Genetic Therapy ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,Lipids ,2500 General Materials Science ,0104 chemical sciences ,Polyethylene Glycols/chemistry ,chemistry ,10036 Medical Clinic ,Colloidal gold ,Liposomes ,Biophysics ,RNA, Messenger/chemistry ,RNA ,Nanoparticles ,Nanoparticles/chemistry ,Small Interfering/chemistry ,0210 nano-technology ,Liposomes/chemistry ,Macromolecule - Abstract
The success of Onpattro™ (patisiran) clearly demonstrates the utility of lipid nanoparticle (LNP) systems for enabling gene therapies. These systems are composed of ionizable cationic lipids, phospholipid, cholesterol, and polyethylene glycol (PEG)-lipids, and are produced through rapid-mixing of an ethanolic-lipid solution with an acidic aqueous solution followed by dialysis into neutralizing buffer. A detailed understanding of the mechanism of LNP formation is crucial to improving LNP design. Here we use cryogenic transmission electron microscopy and fluorescence techniques to further demonstrate that LNP are formed through the fusion of precursor, pH-sensitive liposomes into large electron-dense core structures as the pH is neutralized. Next, we show that the fusion process is limited by the accumulation of PEG-lipid on the emerging particle. Finally, we show that the fusion-dependent mechanism of formation also applies to LNP containing macromolecular payloads including mRNA, DNA vectors, and gold nanoparticles.
- Published
- 2019
48. On Condorelli inequality for log-concave demand
- Author
-
Qingyun Gui and Yi C. Huang
- Subjects
Economics and Econometrics ,Finance - Published
- 2022
49. Intercalating Single-Atom Metal Centers into an Organic Monolayer with a Full-Sample Coverage
- Author
-
Yi C. Zhang and David Y. Lee
- Subjects
Materials science ,Intercalation (chemistry) ,Substrate (chemistry) ,02 engineering and technology ,Surfaces and Interfaces ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Full sample ,0104 chemical sciences ,Metal ,Crystallography ,visual_art ,Atom ,Monolayer ,Electrochemistry ,visual_art.visual_art_medium ,General Materials Science ,0210 nano-technology ,Spectroscopy - Abstract
Thiolate self-assembled monolayers (SAMs) have been widely used as a straightforward method to functionalize the surface of a common substrate with selective organic functional groups. Here we describe a process that further introduces isolated metal centers into an organic SAM using solutions of metallic porphyrin so that different organic groups and metal single-atoms can be simultaneously exposed on top of the surface. The entire process employs only common laboratory equipment and mild-temperature (100 °C) incubation to create a full-sample (cm
- Published
- 2018
50. Characterization of Lipid Nanoparticles Containing Ionizable Cationic Lipids Using Design-of-Experiments Approach
- Author
-
Yuen Yi C. Tam, Sam Chen, Roy van der Meel, Ariel Huynh, Jayesh A. Kulkarni, Pieter R. Cullis, Takeshi Terada, Precision Medicine, and ICMS Core
- Subjects
Vesicle ,Dispersity ,Cationic polymerization ,Excipient ,Nanoparticle ,02 engineering and technology ,Surfaces and Interfaces ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Phosphatidylcholine ,Electrochemistry ,medicine ,Biophysics ,General Materials Science ,Particle size ,0210 nano-technology ,Dialysis (biochemistry) ,Spectroscopy ,medicine.drug - Abstract
Lipid nanoparticles (LNPs) containing short-interfering RNA (LNP-siRNA systems) are a promising approach for silencing disease-causing genes in hepatocytes following intravenous administration. LNP-siRNA systems are generated by rapid mixing of lipids in ethanol with siRNA in aqueous buffer (pH 4.0) where the ionizable lipid is positively charged, followed by dialysis to remove ethanol and to raise the pH to 7.4. Ionizable cationic lipids are the critical excipient in LNP systems as they drive entrapment and intracellular delivery. A recent study on the formation of LNP-siRNA systems suggested that ionizable cationic lipids segregate from other lipid components upon charge neutralization to form an amorphous oil droplet in the core of LNPs. This leads to a decrease in intervesicle electrostatic repulsion, thereby engendering fusion of small vesicles to form final LNPs of increased size. In this study, we prepared LNP-siRNA systems containing four lipid components (hydrogenated soy phosphatidylcholine, cholesterol, PEG-lipid, and 1,2-dioleoyl-3-dimethylammonium propane) by microfluidic mixing. The effects of preparation parameters [lipid concentration, flow rate ratio (FRR), and total flow rate], dialysis process, and complex formation between siRNA and ionizable cationic lipids on the physicochemical properties [siRNA entrapment on the particle size and polydispersity index (PDI)] were investigated using a design of experiments approach. The results for the preparation parameters showed no impact on siRNA encapsulation, but lipid concentration and FRR significantly affected the particle size and PDI. In addition, the effect of FRR on the particle size was suppressed in the presence of anionic polymers such as siRNA as compared to the case of LNPs alone. More intriguingly, unlike empty LNPs, a decrease in the PDI and an increase in the particle size occurred after dialysis in the LNP-siRNA systems. Such changes by dialysis were suppressed at FRR = 1. These findings provide useful information to guide the development and manufacturing conditions for LNP-siRNA systems.
- Published
- 2021
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