Biodegradable polymeric nanoparticles based drug delivery systems

Many-particle charged-particle plasma simulations using spatial meshes for the electromagnetic field solutions, particle-in-cell (PIC) merged with Monte Carlo collision (MCC) calculations, are coming into wide use for application to partially ionized gases. The author emphasizes the development of PIC computer experiments since the 1950s starting with one-dimensional (1-D) charged-sheet models, the addition of the mesh, and fast direct Poisson equation solvers for 2-D and 3-D. Details are provided for adding the collisions between the charged particles and neutral atoms. The result is many-particle simulations with many of the features met in low-temperature collision plasmas; for example, with applications to plasma-assisted materials processing, but also related to warmer plasmas at the edges of magnetized fusion plasmas. >

Particle-in-Cell Charged Particle Simulations, plus Monte Carlo Collisions with Neutral Atoms, PIC-MCC

http://systemarchitect.mit.edu/docs/selva12b.pdf

A survey and assessment of the capabilities of Cubesats for Earth observation

The capacity of human norovirus (NoV), which causes >90% of global epidemic nonbacterial gastroenteritis, to infect a subset of people persistently may contribute to its spread. How such enteric viruses establish persistent infections is not well understood. We found that antibiotics prevented persistent murine norovirus (MNoV) infection, an effect that was reversed by replenishment of the bacterial microbiota. Antibiotics did not prevent tissue infection or affect systemic viral replication but acted specifically in the intestine. The receptor for the antiviral cytokine interferon-λ, Ifnlr1, as well as the transcription factors Stat1 and Irf3, were required for antibiotics to prevent viral persistence. Thus, the bacterial microbiome fosters enteric viral persistence in a manner counteracted by specific components of the innate immune system.

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Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection

Human noroviruses (HuNoVs) are a leading cause of foodborne disease and severe childhood diarrhea, and they cause a majority of the gastroenteritis outbreaks worldwide. However, the development of effective and long-lasting HuNoV vaccines and therapeutics has been greatly hindered by their uncultivability. We recently demonstrated that a HuNoV replicates in human B cells, and that commensal bacteria serve as a cofactor for this infection. In this protocol, we provide detailed methods for culturing the GII.4-Sydney HuNoV strain directly in human B cells, and in a coculture system in which the virus must cross a confluent epithelial barrier to access underlying B cells. We also describe methods for bacterial stimulation of HuNoV B cell infection and for measuring viral attachment to the surface of B cells. Finally, we highlight variables that contribute to the efficiency of viral replication in this system. Infection assays require 3 d and attachment assays require 3 h. Analysis of infection or attachment samples, including RNA extraction and RT-qPCR, requires ∼6 h.

/pdf/human-norovirus-culture-in-b-cells-5qwdurho9q.pdf

Human norovirus culture in B cells

Microfold (M) cells are specialized intestinal epithelial cells that internalize particulate antigens and aid in the establishment of immune responses to enteric pathogens. M cells have also been suggested as a portal for pathogen entry into the host. While virus particles have been observed in M cells, it is not known whether viruses use M cells to initiate a productive infection. Noroviruses (NoVs) are single-stranded RNA viruses that infect host organisms via the fecal-oral route. Murine NoV (MNV) infects intestinal macrophages and dendritic cells and provides a tractable experimental system for understanding how an enteric virus overcomes the intestinal epithelial barrier to infect underlying target cells. We found that replication of two divergent MNV strains was reduced in mice depleted of M cells. Reoviruses are double-stranded RNA viruses that infect hosts via respiratory or enteric routes. In contrast to MNV, reovirus infects enterocytes in the intestine. Despite differences in cell tropism, reovirus infection was also reduced in M cell-depleted mice. These data demonstrate that M cells are required for the pathogenesis of two unrelated enteric viruses that replicate in different cell types within the intestine.

IMPORTANCE To successfully infect their hosts, pathogens that infect via the gastrointestinal tract must overcome the multilayered system of host defenses. Microfold (M) cells are specialized intestinal epithelial cells that internalize particulate antigens and aid in the establishment of immune responses to enteric pathogens. Virus particles have been observed within M cells. However, it is not known whether viruses use M cells to initiate a productive infection. To address this question, we use MNV and reovirus, two enteric viruses that replicate in different cell types in the intestine, intestinal epithelial cells for reovirus and intestinal mononuclear phagocytes for MNV. Interestingly, MNV- and reovirus-infected mice depleted of M cells showed reduced viral loads in the intestine. Thus, our work demonstrates the importance of M cells in the pathogenesis of enteric viruses irrespective of the target cell type in which the virus replicates.

Efficient Norovirus and Reovirus Replication in the Mouse Intestine Requires Microfold (M) Cells

Noroviruses (NoVs) are the causative agent of the vast majority of nonbacterial gastroenteritis worldwide. Due to the inability to culture human NoVs and the inability to orally infect a small animal model, little is known about the initial steps of viral entry. One particular step that is not understood is how NoVs breach the intestinal epithelial barrier. Murine NoV (MNV) is the only NoV that can be propagated in vitro by infecting murine macrophages and dendritic cells, making this virus an attractive model for studies of different aspects of NoV biology. Polarized murine intestinal epithelial mICcl2 cells were used to investigate how MNV interacts with and crosses the intestinal epithelium. In this in vitro model of the follicle-associated epithelium (FAE), MNV is transported across the polarized cell monolayer in the absence of viral replication or disruption of tight junctions by a distinct epithelial cell with microfold (M) cell properties. In addition to transporting MNV, these M-like cells also transcytose microbeads and express an IgA receptor. Interestingly, B myeloma cells cultured in the basolateral compartment underlying the epithelial monolayer did not alter the number of M-like cells but increased their transcytotic activity. Our data demonstrate that MNV can cross an intact intestinal epithelial monolayer in vitro by hijacking the M-like cells' intrinsic transcytotic pathway and suggest a potential mechanism for MNV entry into the host.

Murine Norovirus Transcytosis across an In Vitro Polarized Murine Intestinal Epithelial Monolayer Is Mediated by M-Like Cells

The particle-based coupling between background gas flows in vacuum test facilities and neutral ingestion into Hall effect thrusters is investigated. An analytical model of the facility background flow environment is developed to accommodate facilities with different geometries and pump placements, as well as compute the ingested flow rate of background neutrals into a given Hall effect thruster. The ingested flow rates computed by the model are shown to predict previous empirical datasets taken using the 5 kW P5, the 6 kW H6, and the 1.5 kW SPT-100 Hall effect thrusters in different test facilities to within the experimental uncertainty. When compared to predictions generated assuming ingestion by the random flux of neutral particles, the ingested flow rates computed by the background flow model are shown to be 40 to 70% closer to the empirical measurements without requiring any semiempirical inputs. It is also shown that the neutral ingestion at a fixed facility pressure can vary by as much as 91%, sugge...

Background Flow Model of Hall Thruster Neutral Ingestion

This paper will present our understanding of the hollow cathode barium depletion mechanism and the design required to achieve the required life.

Extending hollow cathode life for electric propulsion in long-term missions

A new electrostatic thruster technology is under development at the University of Michigan using nanoparticles as propellant with micro‐ and nano‐electromechanical systems. Termed the nanoparticle field extraction thruster (nanoFET), this highly integrated propulsion concept is a high efficiency, variable specific impulse engine type that can be readily scalable for a large range of future space science and exploration missions.

/pdf/nanoparticle-electric-propulsion-for-space-exploration-36t62b2lk4.pdf

Thomas M. Liu

Papers

Efficient Norovirus and Reovirus Replication in the Mouse Intestine Requires Microfold (M) Cells

Murine Norovirus Transcytosis across an In Vitro Polarized Murine Intestinal Epithelial Monolayer Is Mediated by M-Like Cells

Background Flow Model of Hall Thruster Neutral Ingestion

Extending hollow cathode life for electric propulsion in long-term missions

Nanoparticle Electric Propulsion for Space Exploration