Adaptive Modal Identification for Flutter Suppression Control

In this paper, we will develop an adaptive modal identification method for identifying the frequencies and damping of a flutter mode based on model-reference adaptive control (MRAC) and least-squares methods. The least-squares parameter estimation will achieve parameter convergence in the presence of persistent excitation whereas the MRAC parameter estimation does not guarantee parameter convergence. Two adaptive flutter suppression control approaches are developed: one based on MRAC and the other based on the least-squares method. The MRAC flutter suppression control is designed as an integral part of the parameter estimation where the feedback signal is used to estimate the modal information. On the other hand, the separation principle of control and estimation is applied to the least-squares method. The least-squares modal identification is used to perform parameter estimation

Examining sensory ability, feature matching, and assessment-based adaptation for a brain-computer interface using the steady-state visually evoked potential

This is an Accepted Manuscript of an article published by Taylor & Francis in Disability and Rehabilitation: Assistive Technology on 01/31/2018, available online: http://www.tandfonline.com/10.1080/17483107.2018.1428369.PURPOSE:We investigated how overt visual attention and oculomotor control influence successful use of a visual feedback brain-computer interface (BCI) for accessing augmentative and alternative communication (AAC) devices in a heterogeneous population of individuals with profound neuromotor impairments. BCIs are often tested within a single patient population limiting generalization of results. This study focuses on examining individual sensory abilities with an eye toward possible interface adaptations to improve device performance. METHODS: Five individuals with a range of neuromotor disorders participated in four-choice BCI control task involving the steady state visually evoked potential. The BCI graphical interface was designed to simulate a commercial AAC device to examine whether an integrated device could be used successfully by individuals with neuromotor impairment. RESULTS: All participants were able to interact with the BCI and highest performance was found for participants able to employ an overt visual attention strategy. For participants with visual deficits to due to impaired oculomotor control, effective performance increased after accounting for mismatches between the graphical layout and participant visual capabilities. CONCLUSION: As BCIs are translated from research environments to clinical applications, the assessment of BCI-related skills will help facilitate proper device selection and provide individuals who use BCI the greatest likelihood of immediate and long term communicative success. Overall, our results indicate that adaptations can be an effective strategy to reduce barriers and increase access to BCI technology. These efforts should be directed by comprehensive assessments for matching individuals to the most appropriate device to support their complex communication needs. Implications for Rehabilitation Brain computer interfaces using the steady state visually evoked potential can be integrated with an augmentative and alternative communication device to provide access to language and literacy for individuals with neuromotor impairment. Comprehensive assessments are needed to fully understand the sensory, motor, and cognitive abilities of individuals who may use brain-computer interfaces for proper feature matching as selection of the most appropriate device including optimization device layouts and control paradigms. Oculomotor impairments negatively impact brain-computer interfaces that use the steady state visually evoked potential, but modifications to place interface stimuli and communication items in the intact visual field can improve successful outcomes

Isomeric triazines exhibit unique profiles of bioorthogonal reactivity.

Expanding the scope of bioorthogonal reactivity requires access to new and mutually compatible reagents. We report here that 1,2,4-triazines can be tuned to exhibit unique reaction profiles with biocompatible strained alkenes and alkynes. Computational analyses were used to identify candidate orthogonal reactions, and the predictions were experimentally verified. Notably, 5-substituted triazines, unlike their 6-substituted counterparts, undergo rapid [4 + 2] cycloadditions with a sterically encumbered strained alkyne. This unique, sterically controlled reactivity was exploited for dual bioorthogonal labeling. Mutually orthogonal triazines and cycloaddition chemistries will enable new multi-component imaging applications

Enhanced ribosomal association of p27Kip1 mRNA is a mechanism contributing to accumulation during growth arrest

p27(Kip1) regulates the decision to enter into S-phase or withdraw from the cell cycle by establishing an inhibitory threshold above which G(1) cyclin-dependent kinases accumulate before activation. We have used the HL-60 cell line to study regulation of p27 as cells withdraw from the cell cycle following treatment with 12-O-tetra-decanoylphorbol-13-acetate (TPA). We found that the amount of p27 is maximal in G(0) cells, lower in G(1) cells, and undetectable in S-phase cells, In contrast to the protein, the amount of p27 mRNA was the same in these populations, suggesting tliat accumulation of p27 during the cell cycle and as cells withdraw hom the cell cycle is controlled by post-transcriptional mechanisms, In S-phase cells, the degradation of p27 appears to predominate as a regulatory mechanism, In G(0) cells, there was an increase in the synthesis rate of p27, Our data demonstrate that, in G(0) cells, accumulation of p27 is due to an increase in the amount of p27 mRNA in polyribosomes

Population pharmacokinetics of meropenem administered as a prolonged infusion in children with cystic fibrosis

OBJECTIVES: Meropenem is frequently used to treat pulmonary exacerbations in children with cystic fibrosis (CF) in the USA. Prolonged-infusion meropenem improves the time that free drug concentrations remain above the MIC (fT> MIC) in adults, but data in CF children are sparse. We describe the population pharmacokinetics, tolerability and treatment burden of prolonged-infusion meropenem in CF children. METHODS: Thirty children aged 6-17 years with a pulmonary exacerbation received 40 mg/kg meropenem every 8 h; each dose was administered as a 3 h infusion. Pharmacokinetics were determined using population methods in Pmetrics. Monte Carlo simulation was employed to compare 0.5 with 3 h infusions to estimate the probability of pharmacodynamic target attainment (PTA) at 40% fT> MIC. NCT#01429259. RESULTS: A two-compartment model fitted the data best with clearance and volume predicted by body weight. Clearance and volume of the central compartment were 0.41 ± 0.23 L/h/kg and 0.30 ± 0.17 L/kg, respectively. Half-life was 1.11 ± 0.38 h. At MICs of 1, 2 and 4 mg/L, PTAs for the 0.5 h infusion were 87.6%, 70.1% and 35.4%, respectively. The prolonged infusion increased PTAs to >99% for these MICs and achieved 82.8% at 8 mg/L. Of the 30 children, 18 (60%) completed treatment with prolonged infusion; 5 did so at home without any reported burden. Nine patients were changed to a 0.5 h infusion when discharged home. CONCLUSIONS: In these CF children, meropenem clearance was greater compared with published values from non-CF children. Prolonged infusion provided an exposure benefit against pathogens with MICs ≥1 mg/L, was well tolerated and was feasible to administer in the hospital and home settings, the latter depending on perception and family schedule

Control-focused, nonlinear and time-varying modelling of dielectric elastomer actuators with frequency response analysis

Current models of dielectric elastomer actuators (DEAs) are mostly constrained to first principal descriptions that are not well suited to the application of control design due to their computational complexity. In this work we describe an integrated framework for the identification of control focused, data driven and time-varying DEA models that allow advanced analysis of nonlinear system dynamics in the frequency-domain. Experimentally generated input–output data (voltage-displacement) was used to identify control-focused, nonlinear and time-varying dynamic models of a set of film-type DEAs. The model description used was the nonlinear autoregressive with exogenous input structure. Frequency response analysis of the DEA dynamics was performed using generalized frequency response functions, providing insight and a comparison into the time-varying dynamics across a set of DEA actuators. The results demonstrated that models identified within the presented framework provide a compact and accurate description of the system dynamics. The frequency response analysis revealed variation in the time-varying dynamic behaviour of DEAs fabricated to the same specifications. These results suggest that the modelling and analysis framework presented here is a potentially useful tool for future work in guiding DEA actuator design and fabrication for application domains such as soft robotics

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

Carbon‐Enriched Amorphous Hydrogenated Boron Carbide Films for Very‐Low‐k Interlayer Dielectrics

A longstanding challenge in ultralarge‐scale integration has been the continued improvement in low‐dielectric‐constant (low‐k) interlayer dielectric materials and other specialized layers in back‐end‐of‐the‐line interconnect fabrication. Modeled after the success of carbon‐containing organosilicate materials, carbon‐enriched amorphous hydrogenated boron carbide (a‐BxC:Hy) films are grown by plasma‐enhanced chemical vapor deposition from ortho‐carborane and methane. These films contain more extraicosahedral sp3 hydrocarbon groups than nonenriched a‐BxC:Hy films, as revealed by FTIR and NMR spectroscopy, and also exhibit lower dielectric constants than their nonenriched counterparts, notably due to low densities combined with a low distortion and orientation contribution to the total polarizability. Films with dielectric constant as low as 2.5 are reported with excellent electrical stability (leakage current of 10−9 A cm−2 at 2 MV cm−1 and breakdown voltage of >6 MV cm−1), good thermal conductivity of 0.31 ± 0.03 W m−1 K−1, and high projected Young’s modulus of 12 ± 3 GPa. These properties rival those of leading SiOC:H materials, and position a‐BxC:Hy as an important complement to traditional Si‐based materials to meet the complex needs of next‐generation interconnect fabrication.Carbon‐enriched amorphous hydrogenated boron carbide films are demonstrated with dielectric constant (k) as low as 2.5—attributed to low densities combined with network‐rigidifying CH2 bridging groups—as well as excellent electrical, thermal, and mechanical properties, rivaling those of state‐of‐the‐art silicon‐based low‐k dielectric materials.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141869/1/aelm201700116_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141869/2/aelm201700116.pd

Neratinib protects pancreatic beta cells in diabetes

The loss of functional insulin-producing β-cells is a hallmark of diabetes. Mammalian sterile 20-like kinase 1 (MST1) is a key regulator of pancreatic β-cell death and dysfunction; its deficiency restores functional β-cells and normoglycemia. The identification of MST1 inhibitors represents a promising approach for a β-cell-protective diabetes therapy. Here, we identify neratinib, an FDA-approved drug targeting HER2/EGFR dual kinases, as a potent MST1 inhibitor, which improves β-cell survival under multiple diabetogenic conditions in human islets and INS-1E cells. In a pre-clinical study, neratinib attenuates hyperglycemia and improves β-cell function, survival and β-cell mass in type 1 (streptozotocin) and type 2 (obese Leprdb/db) diabetic mouse models. In summary, neratinib is a previously unrecognized inhibitor of MST1 and represents a potential β-cell-protective drug with proof-of-concept in vitro in human islets and in vivo in rodent models of both type 1 and type 2 diabetes