Behavioral uncertainty quantification for data-driven control

This paper explores the problem of uncertainty quantification in the behavioral setting for data-driven control. Building on classical ideas from robust control, the problem is regarded as that of selecting a metric which is best suited to a data-based description of uncertainties. Leveraging on Willems' fundamental lemma, restricted behaviors are viewed as subspaces of fixed dimension, which may be represented by data matrices. Consequently, metrics between restricted behaviors are defined as distances between points on the Grassmannian, i.e., the set of all subspaces of equal dimension in a given vector space. A new metric is defined on the set of restricted behaviors as a direct finite-time counterpart of the classical gap metric. The metric is shown to capture parametric uncertainty for the class of autoregressive (AR) models. Numerical simulations illustrate the value of the new metric with a data-driven mode recognition and control case study.Comment: Submitted to the 61st IEEE Conference on Decision and Contro

Effect of hydrophobic interactions on lower critical solution temperature for poly(N-isopropylacrylamide-co-dopamine methacrylamide) copolymers

For the preparation of thermoresponsive copolymers, for e.g., tissue engineering scaffolds or drug carriers, a precise control of the synthesis parameters to set the lower critical solution temperature (LCST) is required. However, the correlations between molecular parameters and LCST are partially unknown and, furthermore, LCST is defined as an exact temperature, which oversimplifies the real situation. Here, random N-isopropylacrylamide (NIPAM)/dopamine methacrylamide (DMA) copolymers were prepared under a systematical variation of molecular weight and comonomer amount and their LCST in water studied by calorimetry, turbidimetry, and rheology. Structural information was deduced from observed transitions clarifying the contributions of molecular weight, comonomer content, end-group effect or polymerization degree on LCST, which were then statistically modeled. This proved that the LCST can be predicted through molecular structure and conditions of the solutions. While the hydrophobic DMA lowers the LCST especially the onset, polymerization degree has an important but smaller influence over all the whole LCST range.This research was funded by Shenzhen Fundamental Research Funds number KC2014ZDZJ0001A, the Shenzhen Sci & Tech research grant number ZDSYS201507141105130, and the China Postdoctoral Science Foundation Grant number 2018M633119

Hydrogen bonds in blends of poly(N-isopropylacrylamide), poly(n-ethylacrylamide) homopolymers, and carboxymethyl cellulose

Recently, it was reported that the physical crosslinking exhibited by some biopolymers could provide multiple benefits to biomedical applications. In particular, grafting thermoresponsive polymers onto biopolymers may enhance the degradability or offer other features, as thermothickening behavior. Thus, different interactions will affect the different hydrogen bonds and interactions from the physical crosslinking of carboxymethyl cellulose, the lower critical solution temperatures (LCSTs), and the presence of the ions. This work focuses on the study of blends composed of poly(N-isopropylacrylamide), poly(N-ethylacrylamide), and carboxymethyl cellulose in water and water/methanol. The molecular features, thermoresponsive behavior, and gelation phenomena are deeply studied. The ratio defined by both homopolymers will alter the final properties and the gelation of the final structures, showing that the presence of the hydrophilic groups modifies the number and contributions of the diverse hydrogen bonds.The authors want to acknowledge the funding obtained from the National Science Foundation of China (21574086), Shenzhen Fundamental Research Funds (No. KC2014ZDZJ0001A), Shenzhen Sci & Tech research grant (ZDSYS201507141105130), and China Postdoctoral Science Foundation Grant (2018M633119)

Defining NASH from a multi-omics systems biology perspective

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease affecting up to 6.5% of the general population. There is no simple definition of NASH, and the molecular mechanism underlying disease pathogenesis remains elusive. Studies applying single omics technologies have enabled a better understanding of the molecular profiles associated with steatosis and hepatic inflammation—the commonly accepted histologic features for diagnosing NASH, as well as the discovery of novel candidate biomarkers. Multi-omics analysis holds great potential to uncover new insights into disease mechanism through integrating multiple layers of molecular information. Despite the technical and computational challenges associated with such efforts, a few pioneering studies have successfully applied multi-omics technologies to investigate NASH. Here, we review the most recent technological developments in mass spectrometry (MS)-based proteomics, metabolomics, and lipidomics. We summarize multi-omics studies and emerging omics biomarkers in NASH and highlight the biological insights gained through these integrated analyses

Preparation, thermoresponsive behavior, and preliminary biological study of functionalized poly(N-isopropylacrylamide-co-dopamine methacrylamide) copolymers with an organotin(IV) compound

Recent advances focused on smart polymers have demonstrated the numerous advantages regarding other structures because they can adapt the behavior depending on physicochemical properties. In this way, functionalized thermoresponsive polymers with organometallic complexes were profoundly analyzed. Consequently, novel catalytic systems or biomedical devices could be developed. This publication focuses on the facile preparation of poly(N-isopropylacrylamide-co-dopamine methacrylamide) copolymers functionalized with triphenyltin chloride by protonolysis through the -OH of catechol groups. The presence of hydrophobic organotin(IV) derivatives could modify the solubility, thermoresponsive behavior, and other properties regarding pure copolymers. Also, sensitive analysis of the microstructure could help to understand the changes associated with the lower critical solution temperature by rheology, UV-vis spectroscopy, and calorimetry. In addition, a preliminary biological study against MDA-MB-231 cancer cells and peripheral blood mononuclear cells showed that the functionalized copolymers could be a potential platform to be explored in the future in the fight against cancer.The financial support obtained from the National Science Foundation of China (21574086), Shenzhen Fundamental Research Funds (No. KC2014ZDZJ0001A), Shenzhen Sci & Tech research grant (ZDSYS201507141105130) and China Postdoctoral Science Foundation Grant (2018M633119) are acknowledged. Also, these researchers would like to thank the former Ministerio de Ciencia, Innovación y Universidades of Spain (current Ministerio de Ciencia e Innovación of Spain) for the grant RTI2018-094322-B-I00 and the Dirección General de Investigación e Innovación, Consejería de Educación e Investigación de la Comunidad de Madrid for the predoctoral grant PEJD-2017-PRE/BMD-3512 (I. M.-P.)

Chitosan as a Tool for Sustainable Development: A Mini Review

New developments require innovative ecofriendly materials defined by their biocompatibility, biodegradability, and versatility. For that reason, the scientific society is focused on biopolymers such as chitosan, which is the second most abundant in the world after cellulose. These new materials should show good properties in terms of sustainability, circularity, and energy consumption during industrial applications. The idea is to replace traditional raw materials with new ecofriendly materials which contribute to keeping a high production rate but also reducing its environmental impact and the costs. The chitosan shows interesting and unique properties, thus it can be used for different purposes which contributes to the design and development of sustainable novel materials. This helps in promoting sustainability through the use of chitosan and diverse materials based on it. For example, it is a good sustainable alternative for food packaging or it can be used for sustainable agriculture. The chitosan can also reduce the pollution of other industrial processes such as paper production. This mini review collects some of the most important advances for the sustainable use of chitosan for promoting circular economy. Hence, the present review focuses on different aspects of chitosan from its synthesis to multiple applications.Author wants to thank the Erasmus+ KA107 scholarship

Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk

Pituitary tumor development involves clonal expansion stimulated by hormones and growth factors/cytokines. Using mRNA differential display, we found that the bone morphogenetic protein (BMP inhibitor noggin is down-regulated in prolactinomas from dopamine D2-receptor-deficient mice. BMP-4 is overexpressed in prolactinomas taken from dopamine D2-receptor-deficient female mice, but expression of the highly homologous BMP-2 does not differ in normal pituitary tissue and prolactinomas. BMP-4 is overexpressed in other prolactinoma models, including estradiol-induced rat prolactinomas and human prolactinomas, compared with normal tissue and other pituitary adenoma types (Western blot analysis of 48 tumors). BMP-4 stimulates, and noggin blocks, cell proliferation and the expression of c-Myc in human prolactinomas, whereas BMP-4 has no action in other human pituitary tumors. GH3 cells stably transfected with a dominant negative of Smad4 (Smad4dn; a BMP signal cotransducer) or noggin have reduced tumorigenicity in nude mice. Tumor growth recovered in vivo when the Smad4dn expression was lost, proving that BMP-4/Smad4 are involved in tumor development in vivo. BMP-4 and estrogens act through overlapping intracellular signaling mechanisms on GH3 cell proliferation and c-myc expression: they had additive effects at low concentrations but not at saturating doses, and their action was inhibited by blocking either pathway with the reciprocal antagonist (i.e., BMP-4 with ICI 182780 or 17β-estradiol with Smad4dn). Furthermore, coimmunoprecipitation studies demonstrate that under BMP-4 stimulation Smad4 and Smadl physically interact with the estrogen receptor. This previously undescribed prolactinoma pathogenesis mechanism may participate in tumorigenicity in other cells where estrogens and the type β transforming growth factor family have important roles.Facultad de Ciencias ExactasInstituto de Investigaciones Bioquímicas de La Plat

Concentration Effect over Thermoresponse Derived from Organometallic Compounds of Functionalized Poly(N-isopropylacrylamide-co-dopamine Methacrylamide)

The functionalization of smart polymers is opening a new perspective in catalysis, drug carriers and biosensors, due to the fact that they can modulate the response regarding conventional devices. This smart response could be affected by the presence of organometallic complexes in terms of interactions which could affect the physical chemical properties. In this sense, the thermoresponsive behavior of copolymers based on N-isopropylacrylamide (NIPAM) could be affected due to the presence of hydrophobic groups and concentration effect. In this work, the functionalization of a copolymer based on NIPAM and dopamine methacrylamide with different amounts of bis(cyclopentadienyl)titanium (IV) dichloride was carried out. The resulting materials were characterized, showing a clear idea about the mechanism of functionalization through FTIR spectroscopy. The thermoresponsive behavior was also studied for various polymeric solutions in water by UV–vis spectroscopy and calorimetry. The hydrophobic interactions promoted by the organometallic complex could affect the transition associated with the lower critical solution temperature (LCST), specifically, the segments composed by pure NIPAM. That fact would explain the reduction of the width of the LCST-transition, contrary to what could be expected. In addition, the hydrophobicity was tested by the contact angle and also DNA interactions.The authors want to thank the funding obtained from Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, UE) through the project: PGC2018-095364-B-I00

Treatment of chronic viral hepatitis in woodchucks by prolonged intrahepatic expression of interleukin-12

Chronic hepatitis B is a major cause of liver-related death worldwide. Interleukin-12 (IL-12) induction accompanies viral clearance in chronic hepatitis B virus infection. Here, we tested the therapeutic potential of IL-12 gene therapy in woodchucks chronically infected with woodchuck hepatitis virus (WHV), an infection that closely resembles chronic hepatitis B. The woodchucks were treated by intrahepatic injection of a helper-dependent adenoviral vector encoding IL-12 under the control of a liver-specific RU486-responsive promoter. All woodchucks with viral loads below 10(10) viral genomes (vg)/ml showed a marked and sustained reduction of viremia that was accompanied by a reduction in hepatic WHV DNA, a loss of e antigen and surface antigen, and improved liver histology. In contrast, none of the woodchucks with higher viremia levels responded to therapy. The antiviral effect was associated with the induction of T-cell immunity against viral antigens and a reduction of hepatic expression of Foxp3 in the responsive animals. Studies were performed in vitro to elucidate the resistance to therapy in highly viremic woodchucks. These studies showed that lymphocytes from healthy woodchucks or from animals with low viremia levels produced gamma interferon (IFN-gamma) upon IL-12 stimulation, while lymphocytes from woodchucks with high viremia failed to upregulate IFN-gamma in response to IL-12. In conclusion, IL-12-based gene therapy is an efficient approach to treat chronic hepadnavirus infection in woodchucks with viral loads below 10(10) vg/ml. Interestingly, this therapy is able to break immunological tolerance to viral antigens in chronic WHV carriers