Dynamic Facial Prosthetics for Sufferers of Facial Paralysis

BackgroundThis paper discusses the various methods and the materialsfor the fabrication of active artificial facial muscles. Theprimary use for these will be the reanimation of paralysedor atrophied muscles in sufferers of non-recoverableunilateral facial paralysis.MethodThe prosthetic solution described in this paper is based onsensing muscle motion of the contralateral healthy musclesand replicating that motion across a patient’s paralysed sideof the face, via solid state and thin film actuators. Thedevelopment of this facial prosthetic device focused onrecreating a varying intensity smile, with emphasis ontiming, displacement and the appearance of the wrinklesand folds that commonly appear around the nose and eyesduring the expression.An animatronic face was constructed with actuations beingmade to a silicone representation musculature, usingmultiple shape-memory alloy cascades. Alongside theartificial muscle physical prototype, a facial expressionrecognition software system was constructed. This formsthe basis of an automated calibration and reconfigurationsystem for the artificial muscles following implantation, soas to suit the implantee’s unique physiognomy.ResultsAn animatronic model face with silicone musculature wasdesigned and built to evaluate the performance of ShapeMemory Alloy artificial muscles, their power controlcircuitry and software control systems. A dual facial motionsensing system was designed to allow real time control overmodel – a piezoresistive flex sensor to measure physicalmotion, and a computer vision system to evaluate real toartificial muscle performance.Analysis of various facial expressions in real subjects wasmade, which give useful data upon which to base thesystems parameter limits.ConclusionThe system performed well, and the various strengths andshortcomings of the materials and methods are reviewedand considered for the next research phase, when newpolymer based artificial muscles are constructed andevaluated.Key WordsArtificial Muscles, facial prosthetics, stroke rehabilitation,facial paralysis, computer vision, automated facialrecognition

SAP30, a Novel Oncogenic Transcription Factor in High-Risk Neuroblastoma: Clinical Significance and Role in Tumor-Progression, Survival, and Drug Resistance

Neuroblastoma is the most common devastating extracranial solid malignancy in children, accounting for 15% of childhood cancer-related mortality. Despite an intense treatment regimen, approximately 50% of children treated for high-risk neuroblastoma have more aggressive tumor relapse with less than 20% five-year overall survival. Amplification of the oncogene MYCN is associated with a high risk of relapse. However, only 25% of high-risk neuroblastomas are MYCN-amplified, indicating that the rest are driven by factors other than MYCN. Therefore, it is essential to identify novel driver transcription factors but not passenger genes that improve prediction efficacy of therapy response and association with high-risk, progression, stage 4, and survival in neuroblastoma patients. We used three neuroblastoma patient datasets (n=1252 patients) and applied robust bioinformatic data mining tools such as Weighted Gene Co-expression Network Analysis (WGCNA), cisTarget, and Single-Cell Regulatory Network Inference and Clustering (SCENIC) to identify driver transcription factors (regulon) that associate with high-risk, progression, stage, and survival in neuroblastoma patients. Based on the regulon specificity score, we derived a 10-transcription factor signature and prioritized Sin3A Associated Protein 30 (SAP30), given its highest regulon specificity score, especially in high-risk and aggressive stage cohorts. Higher SAP30 expression was found in high-risk neuroblastoma patients and progression-specific patient-derived xenograft tumors than their respective controls. The advanced pharmacogenomic analysis and CRISPR-Cas9 screens indicated that SAP30 essentiality correlated with Cisplatin resistance and further validated in Cisplatin resistant patient-derived xenograft tumor-derived cell lines. SAP30 silencing inhibited cell proliferation, slowed growth and induced cell death in vitro, and reduced tumor burden and size in vivo. Overall, our results indicate that SAP30 is a better prognostic and Cisplatin resistant marker associated with high-risk, stage 4 progression, and poor survival in neuroblastoma patients.https://digitalcommons.unmc.edu/chri_forum/1057/thumbnail.jp

Unravelling the mechanisms of vibrational relaxation in solution

We present a systematic study of the mode-specific vibrational relaxation of NO(2) in six weakly-interacting solvents (perfluorohexane, perfluoromethylcyclohexane, perfluorodecalin, carbon tetrachloride, chloroform, and d-chloroform), chosen to elucidate the dominant energy transfer mechanisms in the solution phase. Broadband transient vibrational absorption spectroscopy has allowed us to extract quantum state-resolved relaxation dynamics of the two distinct NO(2) fragments produced from the 340 nm photolysis of N(2)O(4) → NO(2)(X) + NO(2)(A) and their separate paths to thermal equilibrium. Distinct relaxation pathways are observed for the NO(2) bending and stretching modes, even at energies as high as 7000 cm(–1) above the potential minimum. Vibrational energy transfer is governed by different interaction mechanisms in the various solvent environments, and proceeds with timescales ranging from 20–1100 ps. NO(2) relaxation rates in the perfluorocarbon solvents are identical despite differences in acceptor mode state densities, infrared absorption cross sections, and local solvent structure. Vibrational energy is shown to be transferred to non-vibrational solvent degrees of freedom (V-T) through impulsive collisions with the perfluorocarbon molecules. Conversely, NO(2) relaxation in chlorinated solvents is reliant on vibrational resonances (V-V) while V-T energy transfer is inefficient and thermal excitation of the surrounding solvent molecules inhibits faster vibrational relaxation through direct complexation. Intramolecular vibrational redistribution allows the symmetric stretch of NO(2) to act as a gateway for antisymmetric stretch energy to exit the molecule. This study establishes an unprecedented level of detail for the cooling dynamics of a solvated small molecule, and provides a benchmark system for future theoretical studies of vibrational relaxation processes in solution

The Otterbein Miscellany - May 1965

https://digitalcommons.otterbein.edu/miscellany/1011/thumbnail.jp

Recombination, Solvation and Reaction of CN Radicals Following Ultraviolet Photolysis of ICN in Organic Solvents

The fates of CN radicals produced by ultraviolet (UV) photolysis of ICN in various organic solvents have been examined by transient electronic and vibrational absorption spectroscopy (TEAS and TVAS). Near-UV and visible bands in the TEAS measurement enable direct observation of the CN radicals and their complexes with the solvent molecules. Complementary TVAS measurements probe the products of CN–radical reactions. Geminate recombination to form ICN and INC is a minor pathway on the 150 fs −1300 ps time scales of our experiments in the chosen organic solvents; nonetheless, large infrared transition dipole moments permit direct observation of INC that is vibrationally excited in the CN stretching mode. The time constants for INC vibrational cooling range from 30 ps in tetrahydrofuran (THF) to 1400 ps in more weakly interacting solvents such as chloroform. The major channel for CN removal in the organic solvents is reaction with solvent molecules, as revealed by depletion of solvent absorption bands and growth of product bands in the TVA spectra. HCN is a reaction product of hydrogen atom abstraction in most of the photoexcited solutions, and forms with vibrational excitation in both the C–H and CN stretching modes. The vibrational cooling rate of the CN stretch in HCN depends on the solvent, and follows the same trend as the cooling rate of the CN stretch in INC. However, in acetonitrile solution an additional reaction pathway produces C₃H₃N₂^• radicals, which release HCN on a much longer time scale

Enhanced Astrocytic Ca\u3csup\u3e2+\u3c/sup\u3e Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Status epilepticus (SE), an unremitting seizure, is known to cause a variety of traumatic responses including delayed neuronal death and later cognitive decline. Although excitotoxicity has been implicated in this delayed process, the cellular mechanisms are unclear. Because our previous brain slice studies have shown that chemically induced epileptiform activity can lead to elevated astrocytic Ca2+ signaling and because these signals are able to induce the release of the excitotoxic transmitter glutamate from these glia, we asked whether astrocytes are activated during status epilepticus and whether they contribute to delayed neuronal death in vivo. Using two-photon microscopy in vivo, we show that status epilepticus enhances astrocytic Ca2+ signals for 3 d and that the period of elevated glial Ca2+ signaling is correlated with the period of delayed neuronal death. To ask whether astrocytes contribute to delayed neuronal death, we first administered antagonists which inhibit gliotransmission: MPEP [2-methyl-6-(phenylethynyl)pyridine], a metabotropic glutamate receptor 5 antagonist that blocks astrocytic Ca2+ signals in vivo, and ifenprodil, an NMDA receptor antagonist that reduces the actions of glial-derived glutamate. Administration of these antagonists after SE provided significant neuronal protection raising the potential for a glial contribution to neuronal death. To test this glial hypothesis directly, we loaded Ca2+ chelators selectively into astrocytes after status epilepticus.We demonstrate that the selective attenuation of glial Ca2+ signals leads to neuronal protection. These observations support neurotoxic roles for astrocytic gliotransmission in pathological conditions and identify this process as a novel therapeutic target

Reaction Dynamics of CN Radicals in Acetonitrile Solutions

The bimolecular reactions that follow 267 nm ultraviolet photolysis of ICN in acetonitrile solution have been studied using transient absorption spectroscopy on the picosecond time scale. Time-resolved electronic absorption spectroscopy (TEAS) in the ultraviolet and visible spectral regions observes rapid production and loss (with a decay time constant of 0.6 ± 0.1 ps) of the photolytically generated free CN radicals. Some of these radicals convert to a solvated form which decays with a lifetime of 8.5 ± 2.1 ps. Time-resolved vibrational absorption spectroscopy (TVAS) reveals that the free and solvated CN-radicals undergo geminate recombination with I atoms to make ICN and INC, H atom abstraction reactions, and addition reactions to solvent molecules to make C₃H₃N₂ radical species. These radical products have a characteristic absorption band at 2036 cm^–1 that shifts to 2010 cm^–1 when ICN is photolyzed in CD₃CN. The HCN yield is low, suggesting the addition pathway competes effectively with H atom abstraction from CH₃CN, but the delayed growth of the C₃H₃N₂ radical band is best described by reaction of solvated CN radicals through an unobserved intermediate species. Addition of methanol or tetrahydrofuran as a cosolute promotes H atom abstraction reactions that produce vibrationally hot HCN. The combination of TEAS and TVAS measurements shows that the rate-limiting process for production of ground-state HCN is vibrational cooling, the rate of which is accelerated by the presence of methanol or tetrahydrofuran