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Results suggest that the proposed framework may indeed exploit the hallmarks of spatially explicit ecological approaches and of remote Earth observations. The model reproduces well the observed in situ data. Moreover, it projects in the near term the two species' presence both in space and in time, highlighting the features of the metapopulation dynamics of colonization and extinction, and their expected trends within verifiable timeframes.Above a critical temperature known as the Leidenfrost point (LFP), a heated surface can suspend a liquid droplet above a film of its own vapor. The insulating vapor film can be highly detrimental in metallurgical quenching and thermal control of electronic devices, but may also be harnessed to reduce drag and generate power. Manipulation of the LFP has occurred mostly through experiment, giving rise to a variety of semiempirical models that account for the Rayleigh-Taylor instability, nucleation rates, and superheat limits. However, formulating a truly comprehensive model has been difficult given that the LFP varies dramatically for different fluids and is affected by system pressure, surface roughness, and liquid wettability. Here, we investigate the vapor film instability for small length scales that ultimately sets the collapse condition at the Leidenfrost point. From a linear stability analysis, it is shown that the main film-stabilizing mechanisms are the liquid-vapor surface tension-driven transport of vapor mass and the evaporation at the liquid-vapor interface. Meanwhile, van der Waals interaction between the bulk liquid and the solid substrate across the vapor phase drives film collapse. This physical insight into vapor film dynamics allows us to derive an ab initio, mathematical expression for the Leidenfrost point of a fluid. The expression captures the experimental data on the LFP for different fluids under various surface wettabilities and ambient pressures. selleck For fluids that wet the surface (small intrinsic contact angle), the expression can be simplified to a single, dimensionless number that encapsulates the wetting instability governing the LFP.The voltage-gated Hv1 proton channel is a ubiquitous membrane protein that has roles in a variety of cellular processes, including proton extrusion, pH regulation, production of reactive oxygen species, proliferation of cancer cells, and increased brain damage during ischemic stroke. A crystal structure of an Hv1 construct in a putative closed state has been reported, and structural models for the channel open state have been proposed, but a complete characterization of the Hv1 conformational dynamics under an applied membrane potential has been elusive. We report structural models of the Hv1 voltage-sensing domain (VSD), both in a hyperpolarized state and a depolarized state resulting from voltage-dependent conformational changes during a 10-μs-timescale atomistic molecular dynamics simulation in an explicit membrane environment. In response to a depolarizing membrane potential, the S4 helix undergoes an outward displacement, leading to changes in the VSD internal salt-bridge network, resulting in a reshaping of the permeation pathway and a significant increase in hydrogen bond connectivity throughout the channel. The total gating charge displacement associated with this transition is consistent with experimental estimates. Molecular docking calculations confirm the proposed mechanism for the inhibitory action of 2-guanidinobenzimidazole (2GBI) derived from electrophysiological measurements and mutagenesis. The depolarized structural model is also consistent with the formation of a metal bridge between residues located in the core of the VSD. Taken together, our results suggest that these structural models are representative of the closed and open states of the Hv1 channel.Objective Immunotherapy revolutionized melanoma treatment; however, immune-related adverse events, especially neurotoxicity, may be severe and require early and correct diagnosis as well as early treatment commencement. Methods We report an unusual severe multiorgan manifestation of neurotoxicity after treatment with the anti-PDL1 immune checkpoint inhibitor, nivolumab, and the anticytotoxic T-lymphocyte-associated antigen 4 immune checkpoint inhibitor, ipilimumab, in a 47-year-old male patient with metastatic melanoma. Results The patient developed immune-mediated synovitis and cranial neuritis, followed by longitudinal transverse myelitis, encephalitis, and optic neuritis. Early treatment with high-dose steroids and maintenance therapy with rituximab resulted in a favorable neurologic outcome. Conclusions The frequency of spinal cord involvement and neuronal toxicity after cancer immunotherapy is very low and requires an extensive diagnostic workup to differentiate between disease progression and side effects. Immune checkpoint inhibitors should be discontinued and treatment with corticosteroids should be initiated early as the drug of first choice. Therapy may be escalated by other immune-modulating treatments, such as rituximab.Objective To determine serologic characteristics, frequency, phenotype, paraneoplastic associations, and electrodiagnostic and histopathologic features accompanying contactin-1 autoimmunity. Methods Archived sera known to produce synaptic tissue-based immunofluorescence patterns were reevaluated, and contactin-1 specificity was confirmed by recombinant protein assays. Screening of 233 chronic/relapsing demyelinating neuropathies for additional cases was performed. Results We identified 10 contactin-1 IgG seropositive cases. Frequency of contactin-1 immunoglobulin (Ig) G among tested Mayo Clinic chronic/relapsing demyelinating neuropathies was 2%. Sensory predominant presentations (n = 9, 90%), neuropathic pain (n = 6, 60%), and subacute progression (n = 5, 50%) were commonly encountered among contactin-1 neuropathies. Two patients had chronic immune sensory polyradiculopathy-like phenotype at presentation. Electrodiagnostic studies were consistent with demyelination (slowed conduction velocities and/or prolonsentations may guide immunotherapy selection, especially second-line immunotherapy consideration.

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