Dynamical complexity of discrete time regulatory networks

Genetic regulatory networks are usually modeled by systems of coupled differential equations and by finite state models, better known as logical networks, are also used. In this paper we consider a class of models of regulatory networks which present both discrete and continuous aspects. Our models consist of a network of units, whose states are quantified by a continuous real variable. The state of each unit in the network evolves according to a contractive transformation chosen from a finite collection of possible transformations, according to a rule which depends on the state of the neighboring units. As a first approximation to the complete description of the dynamics of this networks we focus on a global characteristic, the dynamical complexity, related to the proliferation of distinguishable temporal behaviors. In this work we give explicit conditions under which explicit relations between the topological structure of the regulatory network, and the growth rate of the dynamical complexity can be established. We illustrate our results by means of some biologically motivated examples.Comment: 28 pages, 4 figure

Five-year follow-up mortality prognostic index for colorectal patients

Purpose: To identify 5-year survival prognostic variables in patients with colorectal cancer (CRC) and to propose a survival prognostic score that also takes into account changes over time in the patient's health-related quality of life (HRQoL) status. Methods: Prospective observational cohort study of CRC patients. We collected data from their diagnosis, intervention, and at 1, 2, 3, and 5 years following the index intervention, also collecting HRQoL data using the EuroQol-5D-5L (EQ-5D-5L), European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Multivariate Cox proportional models were used. Results: We found predictors of mortality over the 5-year follow-up to be being older; being male; having a higher TNM stage; having a higher lymph node ratio; having a result of CRC surgery classified as R1 or R2; invasion of neighboring organs; having a higher score on the Charlson comorbidity index; having an ASA IV; and having worse scores, worse quality of life, on the EORTC and EQ-5D questionnaires, as compared to those with higher scores in each of those questionnaires respectively. Conclusions: These results allow preventive and controlling measures to be established on long-term follow-up of these patients, based on a few easily measurable variables. Implications for cancer survivors: Patients with colorectal cancer should be monitored more closely depending on the severity of their disease and comorbidities as well as the perceived health-related quality of life, and preventive measures should be established to prevent adverse outcomes and therefore to ensure that better treatment is received. Trial registration: ClinicalTrials.gov identifier: NCT02488161Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported in part by grants from the Instituto de Salud Carlos III and the European Regional Development Fund (PS09/00314, PS09/00910, PS09/00746, PS09/00805, PI09/90460, PI09/90490, PI09/90453, PI09/90441, PI09/90397); the Spanish Ministry of the Economy (PID2020-115738 GB-I00); the Departments of Health (2010111098) and Education, Language Policy and Culture (IT1456-22; IT1598-22; IT-1187–19) of the Basque Government; the Research Committee of Galdakao Hospital; the REDISSEC (Red de Investigación en Servicios de Salud en Enfermedades Crónicas) thematic network of the Instituto de Salud Carlos III; and the Department of Education of the Basque Government through the Consolidated Research Group MATHMODE (IT1456-22) and the Basque Government through BMTF “Mathematical Modeling Applied to Health” Project

Radiant waste heat recovery from steelmaking and glass industry

This paper tackles the problem of industrial waste heat recovery through an unexploited heat transfer mechanism: thermal radiation. Energy intensive industries have a considerable potential of unused radiant heat, which cannot be recovered through existing methods. That potential energy is quantified for the main identified industries: steel and glassmaking. Then, a radiant heat capturing device allowing high temperature heat capture is designed according to process requirements. Finally, recoverable heat is estimated and potential uses are proposed

Reconnaissance observations by CIGIDEN after the 2015 Illapel, Chile earthquake and tsunami

This paper describes the reconnaissance work conducted by researchers from the National Research Center for Integrated Natural Disaster Management (CIGIDEN) between September 23rd and October 2nd in the area affected by the Mw 8.3 Illapel megathrust earthquake, which struck offshore the coast of the Coquimbo Region in central Chile on September 16th , 2015. A first team focused on the seismic performance and effects of the tsunami on public hospitals and on reinforced concrete (RC) buildings. A second team focused on the road network infrastructure. Field work included: (i) a survey on the physical and functional damages of the public hospitals in the Region; (ii) a visual inspection and preliminary damage assessment of 20 RC buildings in the largest cities of the region and an aftershock instrumentation of the Coquimbo hospital; and (iii) the inspection of bridges, pedestrian bridges, and rockfall along overstepped cut slopes of the road network. The overall limited impact of this megathrust earthquake may be explained in part by the long-term efforts made by the country to prepare for such events. Learnings from the 2010 Maule earthquake were evidenced in the successful evacuation along the coast of the country, and the overall good performance of engineered masonry structures, and of RC buildings designed after 2010

Dengue virus genomic variation associated with mosquito adaptation defines the pattern of viral non-coding RNAs and fitness in human cells

The Flavivirus genus includes a large number of medically relevant pathogens that cycle between humans and arthropods. This host alternation imposes a selective pressure on the viral population. Here, we found that dengue virus, the most important viral human pathogen transmitted by insects, evolved a mechanism to differentially regulate the production of viral non-coding RNAs in mosquitos and humans, with a significant impact on viral fitness in each host. Flavivirus infections accumulate non-coding RNAs derived from the viral 3'UTRs (known as sfRNAs), relevant in viral pathogenesis and immune evasion. We found that dengue virus host adaptation leads to the accumulation of different species of sfRNAs in vertebrate and invertebrate cells. This process does not depend on differences in the host machinery; but it was found to be dependent on the selection of specific mutations in the viral 3'UTR. Dissecting the viral population and studying phenotypes of cloned variants, the molecular determinants for the switch in the sfRNA pattern during host change were mapped to a single RNA structure. Point mutations selected in mosquito cells were sufficient to change the pattern of sfRNAs, induce higher type I interferon responses and reduce viral fitness in human cells, explaining the rapid clearance of certain viral variants after host change. In addition, using epidemic and pre-epidemic Zika viruses, similar patterns of sfRNAs were observed in mosquito and human infected cells, but they were different from those observed during dengue virus infections, indicating that distinct selective pressures act on the 3'UTR of these closely related viruses. In summary, we present a novel mechanism by which dengue virus evolved an RNA structure that is under strong selective pressure in the two hosts, as regulator of non-coding RNA accumulation and viral fitness. This work provides new ideas about the impact of host adaptation on the variability and evolution of flavivirus 3'UTRs with possible implications in virulence and viral transmission.Fil: Filomatori, Claudia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Carballeda, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Villordo, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Aguirre, Sebastian. Cedars Sinai Medical Center; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pallarés, Horacio Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Maestre, Ana M.. Cedars Sinai Medical Center; Estados UnidosFil: Sánchez Vargas, Irma. State University of Colorado - Fort Collins; Estados UnidosFil: Blair, Carol D.. State University of Colorado - Fort Collins; Estados UnidosFil: Fabri, Cintia. Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I. Maiztegui"; ArgentinaFil: Morales, Maria A.. Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I. Maiztegui"; ArgentinaFil: Fernandez Sesma, Ana. Cedars Sinai Medical Center; Estados UnidosFil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Five-year follow-up mortality prognostic index for colorectal patients

Correction to: Five-year follow-up mortality prognostic index for colorectal patients. Int J Colorectal Dis. 2023 Jun 24;38(1):177. doi: 10.1007/s00384-023-04472-z. PMID: 37354325.Purpose: To identify 5-year survival prognostic variables in patients with colorectal cancer (CRC) and to propose a survival prognostic score that also takes into account changes over time in the patient's health-related quality of life (HRQoL) status. Methods: Prospective observational cohort study of CRC patients. We collected data from their diagnosis, intervention, and at 1, 2, 3, and 5 years following the index intervention, also collecting HRQoL data using the EuroQol-5D-5L (EQ-5D-5L), European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Multivariate Cox proportional models were used. Results: We found predictors of mortality over the 5-year follow-up to be being older; being male; having a higher TNM stage; having a higher lymph node ratio; having a result of CRC surgery classified as R1 or R2; invasion of neighboring organs; having a higher score on the Charlson comorbidity index; having an ASA IV; and having worse scores, worse quality of life, on the EORTC and EQ-5D questionnaires, as compared to those with higher scores in each of those questionnaires respectively. Conclusions: These results allow preventive and controlling measures to be established on long-term follow-up of these patients, based on a few easily measurable variables. Implications for cancer survivors: Patients with colorectal cancer should be monitored more closely depending on the severity of their disease and comorbidities as well as the perceived health-related quality of life, and preventive measures should be established to prevent adverse outcomes and therefore to ensure that better treatment is received. Trial registration: ClinicalTrials.gov identifier: NCT02488161.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported in part by grants from the Instituto de Salud Carlos III and the European Regional Development Fund (PS09/00314, PS09/00910, PS09/00746, PS09/00805, PI09/90460, PI09/90490, PI09/90453, PI09/90441, PI09/90397); the Spanish Ministry of the Economy (PID2020-115738 GB-I00); the Departments of Health (2010111098) and Education, Language Policy and Culture (IT1456-22; IT1598-22; IT-1187–19) of the Basque Government; the Research Committee of Galdakao Hospital; the REDISSEC (Red de Investigación en Servicios de Salud en Enfermedades Crónicas) thematic network of the Instituto de Salud Carlos III; and the Department of Education of the Basque Government through the Consolidated Research Group MATHMODE (IT1456-22) and the Basque Government through BMTF “Mathematical Modeling Applied to Health” Project.S

MMP-8 Deficiency Increases TLR/RAGE Ligands S100A8 and S100A9 and Exacerbates Lung Inflammation during Endotoxemia

Matrix metalloproteinase-8, released mainly from neutrophils, is a critical regulator of the inflammatory response by its ability to cleave multiple mediators. Herein, we report the results of a model of endotoxemia after intraperitoneal LPS injection in mice lacking MMP-8 and their wildtype counterparts. Control, saline-treated animals showed no differences between genotypes. However, there was an increased lung inflammatory response, with a prominent neutrophilic infiltration in mutant animals after LPS treatment. Using a proteomic approach, we identify alarmins S100A8 and S100A9 as two of the main differences between genotypes. Mice lacking MMP-8 showed a significant increase in these two molecules in lung homogenates, but not in spleen and serum. Mice lacking MMP-8 also showed an increase in MIP-1α levels and a marked activation of the non-canonical NF-κB pathway, with no differences in CXC-chemokines such as MIP-2 or LIX. These results show that MMP-8 can modulate the levels of S100A8 and S100A9 and its absence promotes the lung inflammatory response during endotoxemia