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  1. Abstract Photocoagulation of blood vessels offers unambiguous advantages to current radiofrequency approaches considering the high specificity of blood absorption at available laser wavelengths (e.g., 532 nm and 1.064 µm). Successful treatment of pediatric vascular lesions, such as port-wine stains requiring microvascular hemostasis, has been documented. Although laser treatments have been successful in smaller diameter blood vessels, photocoagulation of larger sized vessels is less effective. The hypothesis for this study is that a primary limitation in laser coagulation of large diameter blood vessels (500–1000 µm) originates from shear stress gradients associated with higher flow velocities along with temperature-dependent viscosity changes. Laser (1.07 µm) coagulation ofmore »blood vessels was tested in the chicken chorio-allantoic membrane (CAM). A finite element model is developed that includes hypothetical limitations in laser coagulation during irradiation. A protocol to specify laser dosimetry is derived from OCT imaging and angiography observations as well as finite element model results. Laser dosimetry is applied in the CAM model to test the experimental hypothesis that blood shear stress and flow velocity are important parameters for laser coagulation and hemostasis of large diameter blood vessels (500–1000 µm). Our experimental results suggest that shear stress and flow velocity are fundamental in the coagulation of large diameter blood vessels (500–1000 µm). Laser dosimetry is proposed and demonstrated for successful coagulation and hemostasis of large diameter CAM blood vessels.« less
    Free, publicly-accessible full text available December 1, 2023
  2. Abstract The response by vaccine developers to the COVID-19 pandemic has been extraordinary with effective vaccines authorized for emergency use in the United States within 1 year of the appearance of the first COVID-19 cases. However, the emergence of SARS-CoV-2 variants and obstacles with the global rollout of new vaccines highlight the need for platforms that are amenable to rapid tuning and stable formulation to facilitate the logistics of vaccine delivery worldwide. We developed a “designer nanoparticle” platform using phage-like particles (PLPs) derived from bacteriophage lambda for a multivalent display of antigens in rigorously defined ratios. Here, we engineered PLPsmore »that display the receptor-binding domain (RBD) protein from SARS-CoV-2 and MERS-CoV, alone (RBD SARS -PLPs and RBD MERS -PLPs) and in combination (hCoV-RBD PLPs). Functionalized particles possess physiochemical properties compatible with pharmaceutical standards and retain antigenicity. Following primary immunization, BALB/c mice immunized with RBD SARS - or RBD MERS -PLPs display serum RBD-specific IgG endpoint and live virus neutralization titers that, in the case of SARS-CoV-2, were comparable to those detected in convalescent plasma from infected patients. Further, these antibody levels remain elevated up to 6 months post-prime. In dose-response studies, immunization with as little as one microgram of RBD SARS -PLPs elicited robust neutralizing antibody responses. Finally, animals immunized with RBD SARS -PLPs, RBD MERS -PLPs, and hCoV-RBD PLPs were protected against SARS-CoV-2 and/or MERS-CoV lung infection and disease. Collectively, these data suggest that the designer PLP system provides a platform for facile and rapid generation of single and multi-target vaccines.« less
    Free, publicly-accessible full text available December 1, 2023
  3. Abstract Fluorescence lifetime imaging microscopy (FLIM) is a powerful tool to quantify molecular compositions and study molecular states in complex cellular environment as the lifetime readings are not biased by fluorophore concentration or excitation power. However, the current methods to generate FLIM images are either computationally intensive or unreliable when the number of photons acquired at each pixel is low. Here we introduce a new deep learning-based method termed flimGANE ( f luorescence l ifetime im aging based on G enerative A dversarial N etwork E stimation) that can rapidly generate accurate and high-quality FLIM images even in the photon-starved conditions.more »We demonstrated our model is up to 2,800 times faster than the gold standard time-domain maximum likelihood estimation ( TD_MLE ) and that flimGANE provides a more accurate analysis of low-photon-count histograms in barcode identification, cellular structure visualization, Förster resonance energy transfer characterization, and metabolic state analysis in live cells. With its advantages in speed and reliability, flimGANE is particularly useful in fundamental biological research and clinical applications, where high-speed analysis is critical.« less
    Free, publicly-accessible full text available December 1, 2023
  4. Free, publicly-accessible full text available July 12, 2023
  5. Free, publicly-accessible full text available June 1, 2023
  6. Grilli, Jacopo (Ed.)
    A major strategy to prevent the spread of COVID-19 is the limiting of in-person contacts. However, limiting contacts is impractical or impossible for the many disabled people who do not live in care facilities but still require caregivers to assist them with activities of daily living. We seek to determine which interventions can best prevent infections of disabled people and their caregivers. To accomplish this, we simulate COVID-19 transmission with a compartmental model that includes susceptible, exposed, asymptomatic, symptomatically ill, hospitalized, and removed/recovered individuals. The networks on which we simulate disease spread incorporate heterogeneity in the risk levels of differentmore »types of interactions, time-dependent lockdown and reopening measures, and interaction distributions for four different groups (caregivers, disabled people, essential workers, and the general population). Of these groups, we find that the probability of becoming infected is largest for caregivers and second largest for disabled people. Consistent with this finding, our analysis of network structure illustrates that caregivers have the largest modal eigenvector centrality of the four groups. We find that two interventions—contact-limiting by all groups and mask-wearing by disabled people and caregivers—most reduce the number of infections in disabled and caregiver populations. We also test which group of people spreads COVID-19 most readily by seeding infections in a subset of each group and comparing the total number of infections as the disease spreads. We find that caregivers are the most potent spreaders of COVID-19, particularly to other caregivers and to disabled people. We test where to use limited infection-blocking vaccine doses most effectively and find that (1) vaccinating caregivers better protects disabled people from infection than vaccinating the general population or essential workers and that (2) vaccinating caregivers protects disabled people from infection about as effectively as vaccinating disabled people themselves. Our results highlight the potential effectiveness of mask-wearing, contact-limiting throughout society, and strategic vaccination for limiting the exposure of disabled people and their caregivers to COVID-19.« less
    Free, publicly-accessible full text available May 18, 2023
  7. Free, publicly-accessible full text available August 1, 2023
  8. Free, publicly-accessible full text available January 1, 2023
  9. Pseudomonas aeruginosa is an increasingly antibiotic-resistant pathogen that causes severe lung infections, burn wound infections, and diabetic foot infections. P. aeruginosa produces the siderophore pyochelin through the use of a non-ribosomal peptide synthetase (NRPS) biosynthetic pathway. Targeting members of siderophore NRPS proteins is one avenue currently under investigation for the development of new antibiotics against antibiotic-resistant organisms. Here, the crystal structure of the pyochelin adenylation domain PchD is reported. The structure was solved to 2.11 Å when co-crystallized with the adenylation inhibitor 5′- O -(N-salicylsulfamoyl)adenosine (salicyl-AMS) and to 1.69 Å with a modified version of salicyl-AMS designed to target an active sitemore »cysteine (4-cyano-salicyl-AMS). In the structures, PchD adopts the adenylation conformation, similar to that reported for AB3403 from Acinetobacter baumannii . Graphical abstract« less
    Free, publicly-accessible full text available April 1, 2023
  10. Free, publicly-accessible full text available March 1, 2023