- Advanced X-ray Imaging Techniques
- Advanced Electron Microscopy Techniques and Applications
- Microbial Natural Products and Biosynthesis
- Digital Holography and Microscopy
- Fungal Biology and Applications
- Laser-Plasma Interactions and Diagnostics
- Mass Spectrometry Techniques and Applications
- Malaria Research and Control
- Ubiquitin and proteasome pathways
- 14-3-3 protein interactions
- Synthesis and Catalytic Reactions
- Bacterial Identification and Susceptibility Testing
- Pharmacological Effects and Toxicity Studies
- Advancements in Photolithography Techniques
- X-ray Spectroscopy and Fluorescence Analysis
- Metabolomics and Mass Spectrometry Studies
- Lightning and Electromagnetic Phenomena
- Drug Transport and Resistance Mechanisms
- Crystallography and Radiation Phenomena
- Infectious Encephalopathies and Encephalitis
- Calibration and Measurement Techniques
- Computational Drug Discovery Methods
- Optical Coherence Tomography Applications
- High voltage insulation and dielectric phenomena
- Synthesis of Indole Derivatives
Northwestern University
2017-2023
Eindhoven University of Technology
2020-2021
Portland VA Medical Center
2014-2015
Drexel University
1938-2015
Oregon Health & Science University
2015
Albert Einstein College of Medicine
2015
Reed College
2014
Goodwin College
1988
University of Illinois Urbana-Champaign
1988
The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by novel chemical route and assessed in vitro activity against multidrug resistant strains of Plasmodium falciparum malaria infections mice. Here we describe the pathway to discovery potent class orally active 4(1H)-quinolone-3-diarylethers. initial prototype, ELQ-233, exhibited low nanomolar IC50 values all tested including clinical isolates harboring...
Next-generation nano and quantum devices have increasingly complex 3D structure. As the dimensions of these shrink to nanoscale, their performance is often governed by interface quality or precise chemical dopant composition. Here we present first phase-sensitive extreme ultraviolet imaging reflectometer. It combines excellent phase stability coherent high-harmonic sources, unique chemical- phase-sensitivity reflectometry, state-of-the-art ptychography algorithms. This tabletop microscope...
ELQ-300 is a preclinical candidate that targets the liver and blood stages of Plasmodium falciparum, as well forms are crucial to transmission disease: gametocytes, zygotes, ookinetes. A significant obstacle clinical development related its physicochemical properties. Its relatively poor aqueous solubility high crystallinity limit absorption degree only low concentrations can be achieved following oral dosing. While these sufficient for therapy, levels too establish an acceptable safety...
Single-dose therapies for malaria have been proposed as a way to reduce the cost and increase effectiveness of antimalarial treatment. However, no compound date has shown single-dose activity against both blood-stage Plasmodium parasites that cause disease liver-stage initiate infection. Here, we describe subset cytochrome bc 1 (cyt ) inhibitors, including novel 4(1 H )-quinolone ELQ-400, with liver, blood, transmission-stage in mouse models malaria. Although cyt inhibitors are generally...
Lensless imaging with short-wavelength light is a promising method for achieving high-resolution, chemically sensitive images of wide variety samples. The use 13 nm illumination particular interest materials science and the next-generation nanofabricated devices. Prior to this work, there was an unmet need microscope that can image general samples extreme ultraviolet light, which requires reflection geometry. Here, we fulfill by performing lensless using high-harmonic beam at grazing...
Protein-protein interaction (PPI) networks are fundamental for cellular processes. Small-molecule PPI enhancers have been shown to be powerful tools fundamentally study PPIs and as starting points potential new therapeutics. Yet, systematic approaches their discovery not widely available, the design prerequisites of "molecular glues" poorly understood. Covalent fragment-based screening can identify chemical these at specific sites in interfaces. We recently reported a mass spectrometry-based...
The total synthesis of tambromycin (1), a recently isolated tetrapeptide, is reported. This unusual natural product possesses highly modified tryptophan-derived indole fragment fused to an α-methylserine-derived oxazoline ring, and unique noncanonical amino acid residue named tambroline (11). A convergent was achieved by 13-step route that leveraged recent developments in the field C–H functionalization prepare complex fragment, as well efficient featured diastereoselective amination homoproline.
The benzodiazepine benzomalvin A/D is a fungally derived specialized metabolite and inhibitor of the substance P receptor NK1, biosynthesized by three-gene nonribosomal peptide synthetase cluster. Here, we utilize fungal artificial chromosomes with metabolomic scoring (FAC-MS) to perform molecular genetic pathway dissection targeted metabolomics analysis assign in vivo role each domain biosynthetic pathway. use FAC-MS identified terminal cyclizing condensation as BenY-CT internal C-domains...
Summary Endocrine resistance in breast cancer treatment is a major clinical hurdle, causing an urgent need for alternative modalities. The suppressive protein-protein interaction (PPI) between Estrogen Receptor alpha (ERα) and the adaptor protein 14-3-3 offers such strategy. Here, we report biological impact of small-molecule ‘molecular glues’ this ERα/14-3-3 PPI by using both fusicoccin-derived semi-synthetic natural products fully synthetic covalent drug-like molecules. We show that...
CaCl2 injected intramuscularly in a mixed solution with procaine-HCl protects guinea pigs against convulsions ordinarily produced by injection of alone.
EUV lithography is promising for addressing upcoming, <10nm nodes the semiconductor industry, but with this promise comes need reliable metrology techniques. In particular, there a actinic mask inspection in which imaging wavelength matches that of intended process, so most relevant defects are detected. Here, we demonstrate tabletop, ptychographic, coherent diffraction (CDI) reflection- and transmission-modes extended samples, using 13 nm high harmonic generation (HHG) source. We achieve...
A phenomenon resembling natural ball lightning can be produced via electrical arcing through silicon. We use lump silicon instead of wafers to achieve higher production rates and larger, longer-lived luminous balls than previously reported. The consist a core surrounded by porous network loosely bound dioxide nanoparticles. find that the carry small net charge on order 10(-12) C propose nanoparticles are electrostatically due this charge.
A grand challenge in semiconductor metrology has been the nondestructive characterization 3D nanostructures and their multilayer structure, interfaces, dopant concentrations. We combine extreme ultraviolet reflectometry with state-of-the-art ptychography imaging algorithms to achieve this goal.
We demonstrate the first reflection-mode, tabletop imaging using 12.7nm illumination via ptychography. This is reflection-mode image any ~13nm source of a general sample. utilize glancing incidence-angles to obtain large field-of-view.
Journal Article Wide Field-of-View Reflection-Mode Ptychographic Imaging Microscope with Tabletop 12.7 nm High Harmonic Illumination Get access Michael Tanksalvala, Tanksalvala JILA, University of Colorado, Boulder USA Search for other works by this author on: Oxford Academic Google Scholar Christina L Porter, Porter Gerrity, Gerrity Galen P Miley, Miley Dept. Chemistry, Northwestern University, Evanston Xiaoshi Zhang, Zhang Kapteyn-Murnane Laboratories, Charles S Bevis, Bevis Elisabeth R...
Ascomycete fungal genomes typically each contain >50 different secondary metabolite biosynthetic gene clusters (BGCs). With an estimated pool of >500,000 ascomycete species on earth, the corresponding chemical potential that could be harnessed for human technological challenges such as disease and agriculture is truly massive. However, vast majority fungal-encoded space uncharted difficult to access due difficulties culturing genetically manipulating most fungi. We report a high-throughput...
We demonstrate high-resolution and wide field-of-view imaging using tabletop 13nm HHG sources in transmission reflection geometries. Additionally, we present preliminary simulations results of complex reflectometry allowing highly-sensitive, non-destructive 3D composition determination.
With increasingly 3D devices becoming the norm, there is a growing need in semiconductor industry and materials science for high spatial resolution, non-destructive metrology techniques capable of determining depth-dependent composition information on devices. We present solution to this problem using ptychographic coherent diffractive imaging (CDI) implemented commercially available, tabletop 13 nm source. design, simulations, preliminary results from our new complex EUV reflectometer,...
We present a tabletop-scale complex-imaging EUV reflectometer that uses grazing- incidence ptychographic imaging to non-destructively determine depth-dependent, spatially-resolved composition with high sensitivity chemical makeup, thin film layer thickness, interface quality and dopant profiles.
Journal Article Ptychographic Complex Imaging Reflectometry for Spatially-Resolved Dopant Profiling Using a Tabletop EUV Source Get access Yuka Esashi, Esashi JILA, University of Colorado, Boulder, Colorado 80309, USA Corresponding author: yuka.esashi@colorado.edu Search other works by this author on: Oxford Academic Google Scholar Christina L Porter, Porter Michael Tanksalvala, Tanksalvala Galen P Miley, Miley Department Chemistry, Northwestern University, Evanston, Illinois 60208, Naoto...