Using reactive dissipative particle dynamics to understand local shape manipulation of polymer vesicles.

Biological cells have long been of interest to researchers due to their capacity to actively control their shape. Accordingly, there is significant interest in generating simplified synthetic protocells that can alter their shape based on an externally or internally generated stimulus. To date, most progress has been made towards controlling the global shape of a protocell, whereas less is known about generating a local shape change. Here, we seek to better understand the possible mechanisms for producing local morphological changes in a popular protocell system, the block copolymer vesicle. Accordingly, we have combined Dissipative Particle Dynamics (DPD) and the Split Reactive Brownian Dynamics algorithm (SRBD) to produce a simulation tool that is capable of modeling the dynamics of self-assembled polymer structures as they undergo chemical reactions. Using this Reactive DPD or RDPD method, we investigate local morphological change driven by either the microinjection of a stimulus or an enzymatically-produced stimulus. We find that sub-vesicle-scale morphological change can be induced by either a solvent stimulus that swells the vesicle membrane, or by a reactant stimulus that alters the chemistry of the block polymer in the membrane corona. Notably, the latter method results in a more persistent local deformation than the former, which we attribute to the slower diffusion of polymer chains relative to the solvent. We quantify this deformation and show that it can be modulated by altering the interaction parameter of the parts of the polymer chain that are affected by the stimulus.

Mass-transfer driven spinodal decomposition in a ternary polymer solution.

Nonsolvent induced phase separation (NIPS) is a widely occuring process used in industrial membrane production, nanotechnology and Nature to produce microstructured polymer materials. A variety of process-dependent morphologies are produced when a polymer solution is exposed to a nonsolvent that, following a period where mass is exchanged, precipitates and solidifies the polymer. Despite years of investigation, both experimental and theoretical, many questions surround the pathways to the microstructures that NIPS can produce. Here, we provide simulation results from a model that simultaneously captures both the processess of solvent/nonsolvent exchange and phase separation. We show that the time it takes the nonsolvent to diffuse to the bottom of the film is an important timescale, and that phase separation is possible at times both much smaller and much larger than this scale. Our results include both one-dimensional simulations of the mass transfer kinetics and two- and three-dimensional simulations of morphologies at both short and long times. We find good qualitative agreement with experimental heuristics, but we conclude that an additional model for the vitrification process will be key for fully explaining experimental observations of microstructure formation.

Treatment of severe acute necrotizing encephalopathy of childhood with interleukin-6 receptor blockade in the first 24 h as add-on immunotherapy shows favorable long-term outcome at 2 years.

BACKGROUND: Acute necrotizing encephalopathy (ANE) of childhood is a rare and devastating infection-associated acute encephalopathy. While there are no consensus treatments for ANE, recent case reports suggest a beneficial role for the use of tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 (IL-6) receptor. The correlation of the timing of add-on tocilizumab in relation to long-term outcome has not been reported. METHODS: We report on the timing of administration of tocilizumab in two patients classified as high-risk using the ANE severity score (ANE-SS) with respect to the long-term outcome at 2 years. RESULTS: Case 1 was a 19-month-old previously well boy who presented to a tertiary children's hospital with seizures, evolving status dystonicus and shock. Case 2 was a three-year-old boy who presented to a peripheral hospital with fever, sepsis and encephalopathy. The patients were transferred to the tertiary intensive care unit and MRI confirmed ANE with extensive brainstem involvement. Case 1 received intravenous immunoglobulin (IVIg), methylprednisolone and tocilizumab at 21, 39 and 53 h respectively. His modified Rankin scale (mRS) at discharge and two years was unchanged at 5. The functional independence measure - for children (WeeFIM) at two years was very low (19/126). Case 2 received dexamethasone at 1 h, methylprednisolone at 21 h and IVIg and tocilizumab at 22 h. The mRS at discharge and two years was 4 and 3 respectively. The WeeFIM score at two years showed substantial improvement (96/126). CONCLUSION: The very early use of interleukin-6 blockade as 'add-on' immunotherapy in the first 24 h demonstrates potential for improving the long-term outcome in patients classified as high-risk using the ANE-SS.

Sensitivity analysis of a novel five-degrees-of-freedom user command controller in people with spinal cord injury and non-injured for full upper extremity neuroprosthesis, wearable powered orthoses and prosthetics.

Sensitivity analysis for a user command controller monitoring head position for artificial control of the proximal upper limb was performed. The controller was evaluated by having subjects complete target matching tasks manipulating a simulated on-screen hand representation to investigate the effects of target location and target speed on performance. Sixteen subjects took part in the study, 11 of whom had sustained cervical spinal cord injuries. The subjects were able to control the on-screen hand with overall low sensitivity of performance with the controller to target position in its five-degrees-of-freedom. The optimal speed was found to be a compromise between low speed and high accuracy but longer completion time and fast speed for short completion time with lower accuracy. The results demonstrated the robustness of the controller across a population of non-injured subjects and those with tetraplegia.

A novel five degree of freedom user command controller in people with spinal cord injury and non-injured for full upper extremity neuroprostheses, wearable powered orthoses and prosthetics.

An independent lifestyle requires the ability to place the hand in the complete workspace in concert with hand grasp and release. A novel user command controller monitoring head position for purpose of controlling hand location and orientation is proposed and demonstrated. The controller detected five degrees of freedom which were applied to upper limb movements including forearm and hand placement in three-dimensional space. The controller was evaluated by having subjects complete tracking tasks manipulating a simulated on-screen upper limb representation. Thirteen of the eighteen subjects assessed using the controller had sustained a spinal cord injury at or above the sixth cervical vertebra. Two of the injured subjects with decreased cervical spine mobility were unable to operate the controller. The remaining subjects performed the tracking tasks effectively after minimal training. This simple five-degree of freedom controller has been proposed for the use by those disabled by upper limb amputation, paralysis, weakness or hypertonicity.