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A series of SARS-CoV-2 variants of concern (VOCs) have evolved in humans during the COVID-19 pandemic—Alpha, Beta, Gamma, Delta, and Omicron. Here, we used global proteomic and genomic analyses during infection to understand the molecular responses driving VOC evolution. We discovered VOC-specific differences in viral RNA and protein expression levels, including for N, Orf6, and Orf9b, and pinpointed several viral mutations responsible. An analysis of the host response to VOC infection and comprehensive interrogation of altered virus-host protein-protein interactions revealed conserved and divergent regulation of biological pathways. For example, regulation of host translation was highly conserved, consistent with suppression of VOC replication in mice using the translation inhibitor plitidepsin. Conversely, modulation of the host inflammatory response was most divergent, where we found Alpha and Beta, but not Omicron BA.1, antagonized interferon stimulated genes (ISGs), a phenotype that correlated with differing levels of Orf6. Additionally, Delta more strongly upregulated proinflammatory genes compared to other VOCs. Systematic comparison of Omicron subvariants revealed BA.5 to have evolved enhanced ISG and proinflammatory gene suppression that similarly correlated with Orf6 expression, effects not seen in BA.4 due to a mutation that disrupts the Orf6-nuclear pore interaction. Our findings describe how VOCs have evolved to fine-tune viral protein expression and protein-protein interactions to evade both innate and adaptive immune responses, offering a likely explanation for increased transmission in humans.One sentence summarySystematic proteomic and genomic analyses of SARS-CoV-2 variants of concern reveal how variant-specific mutations alter viral gene expression, virus-host protein complexes, and the host response to infection with applications to therapy and future pandemic preparedness.

So much is unknown about SIP-its etiology, pathophysiology, best treatment modality, and outcome. Yet the incidence of SIP is increasing as more VLBW infants are surviving and since SIP has been identified as a separate disease from NEC. Because many cases present with an insidious onset, it is imperative that practitioners review all x-rays with SIP in mind. Although SIP is a relatively rare occurrence in the NICU, its potential to increase morbidity and mortality in premature infants warrants further research to improve outcomes.

The formation of post-detonation ‘particle’ jets is widely observed in many problems associated with particle dispersal from explosives. This paper analyzes experimental observations to examine the mechanism for formation and growth of such particle jetting instabilities, and to propose a model to address the issues of jetting growth at a macroscopic level. The experiments involve cylindrical charges with a range of central explosive masses for dispersal of dry solid powder, pure liquid, or a hybrid mixture of solid powder and liquid. The results demonstrate that the jets form very early, and that the number of jets is dependent on shock pressure at the charge perimeter, within the range of particle sizes studied. The jetting instabilities may therefore be initiated by shock interaction with the dense solid particle interfaces near the charge surface, followed by early jet growth through transverse particle motion from the interaction of shocked and turbulent wake flow around the particles. From the experiments, a macroscopic model is proposed, in which an edge perturbation on a scale proportional to the number of jets as a function of shock pressure is employed, and the subsequent transverse particle motion is controlled by an attraction function. The model is implemented in the Chinook hydrocode, which is capable of modeling the initiation and growth of particle jetting structures in large-scale dispersal, and the results are validated against experiments.

The Explosive dispersal of densely-packed metal particles in cylindrical RDX-based charges was studied numerically in support of experimental trials. Simulations were conducted using a reactive multiphase fluid dynamic code. Fundamental studies using a large-scale explosive were performed to show scaling phenomena while avoiding potential initiation and critical diameter effects. Spherical tungsten particles were applied in high metal mass fraction cylindrical and spherical charges in two configurations: a particle matrix uniformly embedded in a solid explosive versus an annular shell of particles surrounding a high-explosive core. The effect of particle number density was investigated by varying the nominal particle diameter from 27 to 120 microns while maintaining a constant metal mass fraction. Results were compared with steel particles to evaluate the influence of material density dispersal. Preliminary laboratory-scale simulations were performed using the anticipated experimental configuration for the High Explosives R&D facility at Eglin AFB trials. The effect of particle size and density were investigated, and information to assist in the experiments was obtained. Results were consistent with the fundamental study involving the large-scale explosives, particularly the shape of the cylindrical dispersed dense particle slug, and the relative performance of the large and small particles.

Hypercalcemia is a manifestation of a variety of both benign and malignant diseases. These conditions are not mutually exclusive, and we present a case report of a patient first diagnosed with the classic findings of multiple myeloma who, after appropriate therapy, demonstrated persistent hypercalcemia and was found on further testing to have an elevated parathormone level (PTH) and scintigraphic evidence of a benign parathyroid adenoma. Hypercalcemia responded to excision of the parathyroid adenoma. There are only 18 similar cases reported in the medical literature.