With the resurgence of illnesses, such as measles, it is of utmost importance that a high percentage of the local and global population be vaccinated. Diseases, such as measles, HepB, Hib, and others, are suppressed when 93%–95% of a population has been vaccinated against them, generating herd immunity. Lack of vaccination can lead to lifelong consequences. Barriers to vaccination include costs, lack of healthcare worker knowledge, reliance on cold chain storage, age, and personal beliefs. Vaccinations are usually administered as subcutaneous or intramuscular injections, though some oral vaccines exist. The use of intradermal or intramuscular electroporation (ID-EP and IM-EP) as an adjuvant has demonstrated benefits over traditional vaccination methods, while also having some issues, which require careful consideration. Issues for consideration include a lack of standardized equipment and pulsing protocols while benefits include dose sparing, long-term immunogenicity, and higher titer levels after a single dose compared to the gold standard. ID-EP has been shown to have better transfection rates over IM-EP, while IM-EP has demonstrated faster seroconversion rates (SRs) over IM injection alone. Improvements such as standardizing equipment with larger injection volumes, multiple EP site locations and/or disposable, predosed, lyophilized vaccine cartridges could contribute to more rapid deployment of vaccines without relying on cold chain storage and trained healthcare workers, at a reduced cost while still providing adequate levels of immunity against disease.

Chronic skin wounds are hypoxic and are stalled in a pro-inflammatory state. Hemoglobin (Hb)-based oxygen carriers have shown potential in increasing oxygen delivery to aid wound healing. Macrophages also take up Hb, thus altering their phenotype and the regulation of inflammation. Herein, we compared the effect of Hb and polymerized Hbs (PolyHbs) on the phenotype of human macrophages. Macrophages were incubated with Hb or different forms of PolyHbs, and the inflammatory secretion profile was analyzed. PolyHbs were produced by polymerizing Hb in the relaxed (R) or tense (T) quaternary state and by varying the molar ratio of the glutaraldehyde crosslinking agent to Hb. Hb decreased the secretion of most measured factors. PolyHb treatment led to generally similar secretion profiles; however, Hb had more similar trends to R-state PolyHb. Ingenuity pathway analysis predicted positive outcomes in wound healing and angiogenesis for T-state PolyHb prepared with a 30:1 (glutaraldehyde:Hb) polymerization ratio. When tested in diabetic mouse wounds, T-state PolyHb resulted in the greatest epidermal thickness and vascular endothelial CD31 staining. Thus, the effects of PolyHb on macrophages are affected by the polymerization ratio and the quaternary state, and T-state PolyHb yields secretion profiles that are most beneficial in wound healing.

Here we present a model to estimate the interaction free energy contribution of each amino acid residue of a given protein. Protein interaction energy is described in terms of per-residue interaction factors, μ. Multibody interactions are implicitly captured in μ through the combination of amino acid terms (γ) guided by local conformation indices (σ). The model enables construction of an interaction factor heat map for a protein in a given fold, allows prima facie assessment of the degree of residue-residue interaction, and facilitates a qualitative and quantitative evaluation of protein association properties. The model was used to compute thermal stability of T4 bacteriophage lysozyme mutants across seven sites. Qualitative assessment of mutational effects provides a straightforward rationale regarding whether a particular site primarily perturbs native or non-native states, or both. The presented model was found to be in good agreement with experimental mutational data (R 2 = 0.73) and suggests an approach by which to convert structure space into energy space.

Magnetic resonance imaging (MRI) is a powerful diagnostic tool that has become the imaging modality of choice for soft-tissue visualization in radiation therapy. Emerging technologies aim to integrate MRI with a medical linear accelerator to form novel cancer therapy systems (MR-linac), but the design of these systems to date relies on heuristic procedures. This paper develops an exact, optimization-based approach for magnet design that 1) incorporates the most accurate physics calculations to date, 2) determines precisely the relative spatial location, size, and current magnitude of the magnetic coils, 3) guarantees field homogeneity inside the imaging volume, 4) produces configurations that satisfy, for the first time, small-footprint feasibility constraints required for MR-linacs. Our approach leverages modern mixed-integer programming (MIP), enabling significant flexibility in magnet design generation, e.g., controlling the number of coils and enforcing symmetry between magnet poles. Our numerical results demonstrate the superiority of our method versus current mainstream methods.

Based on the insight that only living organisms can be killed (and that killing can proceed much faster than cell-growth), we present an approach for the detection of viable microorganisms that is much faster than currently used culture-based methods. We do so by using microchannel Electrical Impedance Spectroscopy (m-EIS) for real-time detection of cell-death on exposure to a killing-agent. m-EIS relies on the fact that when living-cells with non-zero membrane potentials are exposed to high-frequency AC-field, induced-charges accumulate at the membrane-interface. Cell-death is accompanied by a loss of membrane-potential, and hence charge-storage (capacitance). A proof-of-principle for a clinical-application (detection of living mycobacteria in sputum) is demonstrated. Mycobacterium smegmatis (doubling-time ∼3 hours) and Mycobacterium bovis BCG (doubling-time ∼20 hours) in artificial-sputum are both detected in [Formula: see text]3 hours when exposed to amikacin. Times-to-detection (TTDs) are ∼12 hours and ∼84 hours (3 1/2 days), respectively for culture-based detection using current technologies (BD-MGIT-960[Formula: see text]) for samples containing similar loads of M. smegmatis and M. bovis BCG

Machine perfusion-based organ preservation techniques are prudently transitioning into clinical practice. Although experimental data is compelling, the outcomes in the highly variable clinical donation-transplantation setting are unpredictable. Here, we offer an intermediate tool for pre-clinical assessment of human donor livers. We present a model for ex situ reperfusion of discarded human livers and report on its application in three human livers that have undergone subnormothermic (21°C) machine perfusion as an experimental preservation method. During reperfusion, the livers macroscopically reperfused in the first 15 minutes, and remained visually well-perfused for 3 hours of ex situ reperfusion. Bile production and oxygen consumption were observed throughout ex situ reperfusion. ATP levels increased 4.25-fold during SNMP. Between the end of SNMP and the end of reperfusion ATP levels dropped 45%. ALT levels in blood increased rapidly in the first 30 minutes and ALT release continued to taper off towards the end of perfusion. Release of CRP, TNF-α, IL-1β, and IL-12, IFN-γ was sustained during reperfusion. These findings support the use of this model for the evaluation of novel human liver preservation techniques.

Advances in the high resolution microscopes and digital imaging technologies have allowed us to visualize diffusible signaling cascades from the protein receptors in the cell membrane to the nucleus. As multi-omics biology evolves over time, building predictable DNA-RNA-protein expression, protein-protein interaction networks and thereby spatiotemporal dynamics of molecular events will help us to uncover differences on cell morphology and physiology between normal and disease states. Here we present an update on optical, fluorescence and electron transmitted microscopes and mass spectrometer imaging technologies and various ways we can apply them for biological discovery and diagnose of human diseases.

A simple first-principles mathematical model is developed to predict the performance of a micro photosynthetic power cell ([Formula: see text]PSC), an electrochemical device which generates electricity by harnessing electrons from photosynthesis in the presence of light. A lumped parameter approach is used to develop a model in which the electrochemical kinetic rate constants and diffusion effects are lumped into a single characteristic rate constant [Formula: see text]. A non-parametric estimation of [Formula: see text] for the [Formula: see text]PSC is performed by minimizing the sum square errors (SSE) between the experimental and model predicted current and voltages. The developed model is validated by comparing the model predicted [Formula: see text] characteristics with experimental data not used in the parameter estimation. Sensitivity analysis of the design parameters and the operational parameters reveal interesting insights for performance enhancement. Analysis of the model also suggests that there are two different operating regimes that are observed in this [Formula: see text]PSC. This modeling approach can be used in other designs of [Formula: see text]PSCs for performance enhancement studies.