WH-MOEA: A Multi-Objective Evolutionary Algorithm for Wiener-Hammerstein System Identification. A Novel Approach for Trade-Off Analysis Between Complexity and Accuracy

[EN] Several approaches have been presented to identify Wiener-Hammerstein models, most of them starting from a linear dynamic model whose poles and zeros are distributed around the static non- linearity. To achieve good precision in the estimation, the Best Linear Approximation (BLA) has usually been used to represent the linear dynamics, while static non-linearity has been arbitrarily parameterised without considering model complexity. In this paper, identification of Wiener, Hammerstein or Wiener-Hammerstein models is stated as a multiobjective optimisation problem (MOP), with a trade-off between accuracy and model complexity. Precision is quantified with the Mean-Absolute-Error (MAE) between the real and estimated output, while complexity is based on the number of poles, zeros and points of the static non- linearity. To solve the MOP, WH-MOEA, a new multiobjective evolutionary algorithm (MOEA) is proposed. From a linear structure, WH-MOEA will generate a set of optimal models considering a static non-linearity with a variable number of points. Using WH-MOEA, a procedure is also proposed to analyse various linear structures with different numbers of poles and zeros (known as design concepts). A comparison of the Pareto fronts of each design concept allows a more in-depth analysis to select the most appropriate model according to the user¿s needs. Finally, a complex numerical example and a real thermal process based on a Peltier cell are identified, showing the procedure¿s goodness. The results show that it can be useful to consider the simultaneously precision and complexity of a block-oriented model (Wiener, Hammerstein or Wiener- Hammerstein) in a non-linear process identification.This work was supported in part by the Ministerio de Ciencia, Innovación y Universidades, Spain, under Grant RTI2018-096904-B-I00-AR, and in part by the Salesian Polytechnic University of Ecuador through a Ph.D. scholarships granted to J. Zambrano.Zambrano, J.; Sanchís Saez, J.; Herrero Durá, JM.; Martínez Iranzo, MA. (2020). WH-MOEA: A Multi-Objective Evolutionary Algorithm for Wiener-Hammerstein System Identification. A Novel Approach for Trade-Off Analysis Between Complexity and Accuracy. IEEE Access. 8:228655-228674. https://doi.org/10.1109/ACCESS.2020.3046352228655228674

Promoter hypermethylation of the AE2/SLC4A2 gene in PBC

Primary biliary cholangitis (PBC) is a chronic immuneassociated cholestatic liver disease with unclear complex/multifactorial etiopathogenesis affecting mostly middle-aged women. Patients with PBC exhibit reduced expression of the AE2/SLC4A2 gene. Herein, we found that AE2 promoter regions are hypermethylated in the liver and peripheral blood mononuclear cells of patients with PBC. This increased methylation is associated with downregulated AE2-gene expression, which might contribute to the pathogenesis of PBC. Therefore, novel epigenetic targets may improve treatment in patients with PBC who respond poorly to current pharmacological therapies

3D printing as an enabling technology to implement maritime plastic Circular Economy

CircularSeas European Project, as part of the European Union Circular Economy [1], aims at promoting the Green Economy by encouraging the development of green products, parts and components by Maritime Industries. The strategy is a combination of Circular Economy principles, with the use of ocean plastic waste for developing new greener materials, and the uptake of advanced manufacturing technology, 3D printing, flexible enough to adapt to the manufacturing conditions for new eco-innovative small and medium parts and components. The paper presents the ongoing research in the project about strategies to introduce Circular Economy in the maritime sector from plastic wastes. This first prospective phase is focused on a series of interviews with each node stakeholders. The paper presents the survey results, together with the challenges to be faced for the implementation of Circular Economy in that specific scenario, despite the -apriori- short term low-profit disadvantages

Visual processing speed in hemianopia patients secondary to acquired brain injury: a new assessment methodology

Producción CientíficaBackground: There is a clinical need to identify diagnostic parameters that objectively quantify and monitor the effective visual ability of patients with homonymous visual field defects (HVFDs). Visual processing speed (VPS) is an objective measure of visual ability. It is the reaction time (RT) needed to correctly search and/or reach for a visual stimulus. VPS depends on six main brain processing systems: auditory-cognitive, attentional, working memory, visuocognitive, visuomotor, and executive. We designed a new assessment methodology capable of activating these six systems and measuring RTs to determine the VPS of patients with HVFDs. Methods: New software was designed for assessing subject visual stimulus search and reach times (S-RT and R-RT respectively), measured in seconds. Thirty-two different everyday visual stimuli were divided in four complexity groups that were presented along 8 radial visual field positions at three different eccentricities (10o, 20o, and 30o). Thus, for each HVFD and control subject, 96 S- and R-RT measures related to VPS were registered. Three additional variables were measured to gather objective data on the validity of the test: eye-hand coordination mistakes (ehcM), eye-hand coordination accuracy (ehcA), and degrees of head movement (dHM, measured by a head-tracker system). HVFD patients and healthy controls (30 each) matched by age and gender were included. Each subject was assessed in a single visit. VPS measurements for HFVD patients and control subjects were compared for the complete test, for each stimulus complexity group, and for each eccentricity. Results: VPS was significantly slower (p < 0.0001) in the HVFD group for the complete test, each stimulus complexity group, and each eccentricity. For the complete test, the VPS of the HVFD patients was 73.0% slower than controls. They also had 335.6% more ehcMs, 41.3% worse ehcA, and 189.0% more dHMs than the controls. Conclusions: Measurement of VPS by this new assessment methodology could be an effective tool for objectively quantifying the visual ability of HVFD patients. Future research should evaluate the effectiveness of this novel method for measuring the impact that any specific neurovisual rehabilitation program has for these patients

Multiple myeloma primary cells show a highly rearranged unbalanced genome with amplifications and homozygous deletions irrespective of the presence of immunoglobulin-related chromosome translocations

Background and Objectives Multiple myeloma (MM) is a malignant plasma cell neoplasia in which genetic studies have shown that genomic changes may affect almost all chromosomes, as shown by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Our objective was the genomic characterization of CD 138 positive primary MM samples by means of a high resolution array CGH platform. Design and Methods For the first time, a high resolution array CGH with more than 40,000 probes, has been used to analyze 26 primary MM samples after the enrichment of CD138-positive plasma cells. Results This approach identified copy number imbalances in all cases. Bioinformatics strategies were optimized to perform data analysis allowing the segregation of hyperdiploid and non-hyperdiploid cases by array CGH. Additional analysis showed that structural chromosome rearrangements were more frequently seen in hyperdiploid cases. We also identified the same Xq21 duplication in nearly 20% of the cases, which originated through unbalanced chromosome translocations. High level amplifications and homozygous deletions were recurrently observed in our series and involved genes with meaningful function in cancer biology. Interpretation and Conclusions High resolution array CGH allowed us to identify copy number changes in 100% of the primary MM samples. We segregated different MM subgroups based on their genomic profiles which made it possible to identify homozygous deletions and amplifications of great genetic relevance in MM

Efficacy of the Combination of Pinaverium Bromide 100mg Plus Simethicone 300mg in Abdominal Pain and Bloating in Irritable Bowel Syndrome: A Randomized, Placebo-controlled Trial

Goals: We aimed to evaluate the efficacy and safety of PB+S (pinaverium bromide 100 mg plus simethicone 300 mg) in patients with irritable bowel syndrome (IBS). Background: IBS is a multifactorial disorder; thus, combination therapy with different mechanisms of action is expected to be useful. PB+S has shown effectiveness in an open-label clinical study in IBS. However, there are no placebo-controlled trials. Materials and Methods: IBS-Rome III patients with abdominal pain/discomfort for at least 2 days within the week prior to baseline assessment were included in this 12-week, randomized, doubleblind, placebo-controlled study of PB+S versus placebo, bid. The primary endpoint was overall symptom improvement, evaluated weekly by the patient (Likert Scale). Secondary endpoints included the weekly improvement in the severity of abdominal pain and bloating assessed both by patients (10-cm Visual Analogue Scale) and investigators (Likert Scale); frequency of Bristol Scale stool types (consistency) evaluated by patients and the IBS Quality of Life scores. Results: A total of 285 patients (female: 83%; 36.5±8.9 y old) received at least 1 dose of PB+S (n=140) or placebo (n=145). No difference was observed in overall symptom improvement between the groups (P=0.13). However, PB+S was superior in abdominal pain (effect size: 31%, P=0.038) and bloating (33%, P=0.019). Patients with IBS-C and IBS-M showed the best improvement in the frequency of stool types with PB+S. No differences were observed in IBS Quality of Life scores and adverse events

Proyecto PREDIRCAM 2. Análisis preliminar de uso y valoración de la plataforma

En la actualidad, la prevalencia de las enfermedades no transmisibles (Non-communicable diseases NCD) y la cantidad de muertes causadas por éstas es muy elevada, en su mayoría, consecuencia del envejecimiento de la población, el aumento de la obesidad y los hábitos de vida sedentarios. En este trabajo se describen el funcionamiento y los resultados preliminares del proyecto Predircam 2, destinado al desarrollo y validación de una plataforma inteligente de tecnologías biomédicas para la monitorización, prevención y tratamiento personalizados del sobrepeso, la obesidad y la prevención de enfermedades asociadas como la diabetes, hipertensión arterial o alteraciones del metabolismo lipídico. El objetivo de este trabajo es presentar los resultados preliminares del análisis del uso de la plataforma, la evaluación de la usabilidad y la valoración de la atención recibida por los pacientes en relación a los profesionales sanitarios

Characterization of endogenous Kv1.3 channel isoforms in T cells

Producción CientíficaVoltage-dependent potassium channel Kv1.3 plays a key role on T-cell activation; however, lack of reliable antibodies has prevented its accurate detection under endogenous circumstances. To overcome this limitation, we created a Jurkat T-cell line with endogenous Kv1.3 channel tagged, to determine the expression, location, and changes upon activation of the native Kv1.3 channels. CRISPR-Cas9 technique was used to insert a Flag-Myc peptide at the C terminus of the KCNA3 gene. Basal or activated channel expression was studied using western blot analysis and imaging techniques. We identified two isoforms of Kv1.3 other than the canonical channel (54 KDa) differing on their N terminus: a longer isoform (70 KDa) and a truncated isoform (43 KDa). All three isoforms were upregulated after T-cell activation. We focused on the functional characterization of the truncated isoform (short form, SF), because it has not been previously described and could be present in the available Kv1.3−/− mice models. Overexpression of SF in HEK cells elicited small amplitude Kv1.3-like currents, which, contrary to canonical Kv1.3, did not induce HEK proliferation. To explore the role of endogenous SF isoform in a native system, we generated both a knockout Jurkat clone and a clone expressing only the SF isoform. Although the canonical isoform (long form) localizes mainly at the plasma membrane, SF remains intracellular, accumulating perinuclearly. Accordingly, SF Jurkat cells did not show Kv1.3 currents and exhibited depolarized resting membrane potential (VM), decreased Ca2+ influx, and a reduction in the [Ca2+]i increase upon stimulation. Functional characterization of these Kv1.3 channel isoforms showed their differential contribution to signaling pathways involved in formation of the immunological synapse. We conclude that alternative translation initiation generates at least three endogenous Kv1.3 channel isoforms in T cells that exhibit different functional roles. For some of these functions, Kv1.3 proteins do not need to form functional plasma membrane channels.Ministerio de Economía y Competitividad (grant PID 2020‐118517RB‐I00)Junta de Castilla y León (grants VA172P20) and (CLU-2019-02)Funds from Institut Curie, INSERM,Agence Nationale de la Recherche RetroTact (ANR‐20CE15‐0009‐01,ANR‐10‐IDEX‐0001‐02 PSL*, and ANR‐11‐LABX‐0043)Fondation pour la Recherche Médicale FRM (EQU202003010280

Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice

The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasio

Amplification of IGH/MYC fusion in clinically aggressive IGH/BCL2-positive germinal center B-cell lymphomas

Activation of an oncogene via its juxtaposition to the IGH locus by a chromosomal translocation or, less frequently, by genomic amplification is considered a major mechanism of B-cell lymphomagenesis. However, amplification of an IGH/oncogene fusion, coined a complicon, is a rare event in human cancers and has been associated with poor outcome and resistance to treatment. In this article are descriptions of two cases of germinal-center-derived B-cell lymphomas with IGH/BCL2 fusion that additionally displayed amplification of an IGH/MYC fusion. As shown by fluorescence in situ hybridization, the first case contained a IGH/MYC complicon in double minutes, whereas the second case showed a BCL2/IGH/MYC complicon on a der(8)t(8;14)t(14;18). Additional molecular cytogenetic and mutation analyses revealed that the first case also contained a chromosomal translocation affecting the BCL6 oncogene and a biallelic inactivation of TP53. The second case harbored a duplication of REL and acquired a translocation affecting IGL and a biallelic inactivation of TP53 during progression. Complicons affecting Igh/Myc have been reported previously in lymphomas of mouse models simultaneously deficient in Tp53 and in genes of the nonhomologous end-joining DNA repair pathway. To the best of our knowledge, this is the first time that IGH/MYC complicons have been reported in human lymphomas. Our findings imply that the two mechanisms resulting in MYC deregulation, that is, translocation and amplification, can occur simultaneously