Analytical results for the multi-objective design of model-predictive control

In model-predictive control (MPC), achieving the best closed-loop performance under a given computational resource is the underlying design consideration. This paper analyzes the MPC design problem with control performance and required computational resource as competing design objectives. The proposed multi-objective design of MPC (MOD-MPC) approach extends current methods that treat control performance and the computational resource separately -- often with the latter as a fixed constraint -- which requires the implementation hardware to be known a priori. The proposed approach focuses on the tuning of structural MPC parameters, namely sampling time and prediction horizon length, to produce a set of optimal choices available to the practitioner. The posed design problem is then analyzed to reveal key properties, including smoothness of the design objectives and parameter bounds, and establish certain validated guarantees. Founded on these properties, necessary and sufficient conditions for an effective and efficient solver are presented, leading to a specialized multi-objective optimizer for the MOD-MPC being proposed. Finally, two real-world control problems are used to illustrate the results of the design approach and importance of the developed conditions for an effective solver of the MOD-MPC problem

Exploring the Abundance, Metabolic Potential, and Gene Expression of Subseafloor Chloroflexi in Million-year-old Oxic and Anoxic Abyssal Clay

Chloroflexi are widespread in subsurface environments, and recent studies indicate that they represent a major fraction of the communities in subseafloor sediment. Here, we compare the abundance, diversity, metabolic potential, and gene expression of Chloroflexi from three abyssal sediment cores from the western North Atlantic Gyre (water depth \u3e5400 m) covering up to 15 million years of sediment deposition, where Chloroflexi were found to represent major components of the community at all sites. Chloroflexi communities die off in oxic red clay over 10 to 15 million years, and gene expression was below detection. In contrast, Chloroflexi abundance and gene expression at the anoxic abyssal clay site increase below the seafloor and peak in 2 to 3 million-year-old sediment, indicating a comparably higher activity. Metatranscriptomes from the anoxic site reveal increased expression of Chloroflexi genes involved in cell wall biogenesis, protein turnover, inorganic ion transport, defense mechanisms and prophages. Phylogenetic analysis shows that these Chloroflexi are closely related to homoacetogenic subseafloor clades and actively transcribe genes involved in sugar fermentations, gluconeogenesis and Wood-Ljungdahl pathway in the subseafloor. Concomitant expression of cell division genes indicates that these putative homoacetogenic Chloroflexi are actively growing in these million-year-old anoxic abyssal sediments

Hydrogel Cross-Linking via Thiol-Reactive Pyridazinediones

Thiol-reactive Michael acceptors are commonly used for the formation of chemically cross-linked hydrogels. In this paper, we address the drawbacks of many Michael acceptors by introducing pyridazinediones as new cross-linking agents. Through the use of pyridazinediones and their mono- or dibrominated analogues, we show that the mechanical strength, swelling ratio, and rate of gelation can all be controlled in a pH-sensitive manner. Moreover, we demonstrate that the degradation of pyridazinedione-gels can be induced by the addition of thiols, thus providing a route to responsive or dynamic gels, and that monobromo-pyridazinedione gels are able to support the proliferation of human cells. We anticipate that our results will provide a valuable and complementary addition to the existing toolkit of cross-linking agents, allowing researchers to tune and rationally design the properties of biomedical hydrogels

Hydrogel Cross-Linking via Thiol-Reactive Pyridazinediones

Thiol-reactive Michael acceptors are commonly used for the formation of chemically cross-linked hydrogels. In this paper, we address the drawbacks of many Michael acceptors by introducing pyridazinediones as new cross-linking agents. Through the use of pyridazinediones and their mono- or dibrominated analogues, we show that the mechanical strength, swelling ratio, and rate of gelation can all be controlled in a pH-sensitive manner. Moreover, we demonstrate that the degradation of pyridazinedione-gels can be induced by the addition of thiols, thus providing a route to responsive or dynamic gels, and that monobromo-pyridazinedione gels are able to support the proliferation of human cells. We anticipate that our results will provide a valuable and complementary addition to the existing toolkit of cross-linking agents, allowing researchers to tune and rationally design the properties of biomedical hydrogels

TCT-170 Development and Validation of a Scoring System for Predicting Clinical Coronary Artery Perforation During Percutaneous Coronary Interventions of Chronic Total Occlusions: The PROGRESS-CTO Perforation Score

Background: Coronary artery perforation is a feared complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and often leads to serious adverse clinical events. Methods: We analyzed clinical and angiographic parameters from 9,618 CTO PCIs in the PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention). Logistic regression prediction modeling was used to identify independently associated variables, and models were internally validated with bootstrapping. Clinical coronary artery perforation was defined as any perforation requiring treatment. Results: The incidence of clinical coronary perforation was 3.8% (n = 367). Five factors were independently associated with perforation and were included in the score: patient age ≥ 65 years, +1 point (OR: 1.79; 95% CI: 1.37-2.33); moderate or severe calcification, +1 point (OR: 1.85; 95% CI: 1.41-2.42); blunt or no stump, +1 point (OR: 1.45; 95% CI: 1.10-1.92); use of antegrade dissection and re-entry strategy, +1 point (OR: 2.43; 95% CI: 1.61-3.69); and use of the retrograde approach, +2 points (OR: 4.02; 95% CI: 2.95-5.46). The resulting score showed acceptable performance on receiver-operating characteristic curve (area under the curve: 0.741; 95% CI: 0.712-0.773). The Hosmer-Lemeshow test indicated good fitness (P = 0.991), and internal validation with bootstrapping demonstrated a good agreement with the model (observed area under the curve: 0.736; 95% bias-corrected CI: 0.706-0.767). Conclusions: The PROGRESS-CTO perforation score is a useful tool for prediction of clinical coronary perforation in CTO PCI. Categories: CORONARY: Complex and Higher Risk Procedures for Indicated Patients (CHIP

Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target.

A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and the molecular heterogeneity of immune infiltrates in gliomas. Here, we report an integrated analysis of 201,986 human glioma, immune, and other stromal cells at the single cell level. In doing so, we discover extensive spatial and molecular heterogeneity in immune infiltrates. We identify molecular signatures for nine distinct myeloid cell subtypes, of which five are independent prognostic indicators of glioma patient survival. Furthermore, we identify S100A4 as a regulator of immune suppressive T and myeloid cells in GBM and demonstrate that deleting S100a4 in non-cancer cells is sufficient to reprogram the immune landscape and significantly improve survival. This study provides insights into spatial, molecular, and functional heterogeneity of glioma and glioma-associated immune cells and demonstrates the utility of this dataset for discovering therapeutic targets for this poorly immunogenic cancer

Tg2576 Cortical Neurons That Express Human Ab Are Susceptible to Extracellular Aβ-Induced, K+ Efflux Dependent Neurodegeneration

Background: One of the key pathological features of AD is the formation of insoluble amyloid plaques. The major constituent of these extracellular plaques is the beta-amyloid peptide (Aβ), although Aβ is also found to accumulate intraneuronally in AD. Due to the slowly progressive nature of the disease, it is likely that neurons are exposed to sublethal concentrations of both intracellular and extracellular Aβ for extended periods of time. Results: In this study, we report that daily exposure to a sublethal concentration of Aβ1-40 (1 μM) for six days induces substantial apoptosis of cortical neurons cultured from Tg2576 mice (which express substantial but sublethal levels of intracellular Aβ). Notably, untreated Tg2576 neurons of similar age did not display any signs of apoptosis, indicating that the level of intracellular Aβ present in these neurons was not the cause of toxicity. Furthermore, wildtype neurons did not become apoptotic under the same chronic Aβ1-40 treatment. We found that this apoptosis was linked to Tg2576 neurons being unable to maintain K⁺ homeostasis following Aβ treatment. Furthermore, blocking K⁺ efflux protected Tg2576 neurons from Aβ-induced neurotoxicity. Interestingly, chronic exposure to 1 μM Aβ1-40 caused the generation of axonal swellings in Tg2576 neurons that contained dense concentrations of hyperphosphorylated tau. These were not observed in wildtype neurons under the same treatment conditions. Conclusions: Our data suggest that when neurons are chronically exposed to sublethal levels of both intra- and extra-cellular Aβ, this causes a K⁺-dependent neurodegeneration that has pathological characteristics similar to AD.9 page(s

A simplified, lossless re-analysis of PAPER-64

We present limits on the 21cm power spectrum from the Epoch of Reionization (EoR) using data from the 64 antenna configuration of the Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER) analyzed through a power spectrum pipeline independent from previous PAPER analyses. Previously reported results from PAPER have been found to contain significant signal loss (Cheng et al. 2018, arxiv:1810.05175). Several lossy steps from previous PAPER pipelines have not been included in this analysis, namely: delay-based foreground filtering, optimal fringe-rate filtering, and empirical covariance-based estimators. Steps which remain in common with previous analyses include redundant calibration and local sidereal time (LST) binning. The power spectra reported here are effectively the result of applying a linear Fourier transform analysis to the calibrated, LST binned data. This analysis also uses more data than previous publications, including the complete available redshift range of $z \sim 7.5$ to $11$. In previous PAPER analyses, many power spectrum measurements were found to be detections of noncosmological power at levels of significance ranging from two to hundreds of times the theoretical noise. Here, excess power is examined using redundancy between baselines and power spectrum jackknives. The upper limits we find on the 21cm power spectrum from reionization are ($1500$ mK)$^{2}$, ($1900$ mK)$^{2}$, ($280$ mK)$^{2}$, ($200$ mK)$^{2}$, ($380$ mK)$^{2}$, ($300$ mK)$^{2}$ at redshifts $z=10.87,\ 9.93,\ 8.68,\ 8.37,\ 8.13,$ and $7.48$, respectively. For reasons described in Cheng et al. 2018 (arxiv:1810.05175), these limits supersede all previous PAPER results (Ali et al. 2018, arxiv:1502.06016).Comment: 28 Pages, 17 Pages, Accepted to AP