Disease re-classi cation via integration of biological networks

Currently, human diseases are classi ed as they were in the late 19th century, by considering only symptoms of the a ected organ. With a growing body of transcriptomic, proteomic, metabolomic and genomics data sets describing diseases, we ask whether the old classi cation still holds in the light of modern biological data. These large-scale and complex biological data can be viewed as networks of inter-connected elements. We propose to rede ne human disease classi cation by considering diseases as systemslevel disorders of the entire cellular system. To do this, we will integrate di erent types of biological data mentioned above. A network-based mathematical model will be designed to represent these integrated data, and computational algorithms and tools will be developed and implemented for its analysis. In this report, a review of the research progress so far will be presented, including 1) a detailed statement of the research problem, 2) a literature survey on relative research topics, 3) reports of on-going work, and 4) future research plans.

Dr1 (NC2) is present at tRNA genes and represses their transcription in human cells

Dr1 (also known as NC2{beta}) was identified as a repressor of RNA polymerase (pol) II transcription. It was subsequently shown to inhibit pol III transcription when expressed at high levels in vitro or in yeast cells. However, endogenous Dr1 was not detected at pol III-transcribed genes in growing yeast. In contrast, we demonstrate that endogenous Dr1 is present at pol III templates in human cells, as is its dimerization partner DRAP1 (also called NC2{alpha}). Expression of tRNA by pol III is selectively enhanced by RNAi-mediated depletion of endogenous human Dr1, but we found no evidence that DRAP1 influences pol III output in vivo. A stable association was detected between endogenous Dr1 and the pol III-specific transcription factor Brf1. This interaction may recruit Dr1 to pol III templates in vivo, as crosslinking to these sites increases following Brf1 induction. On the basis of these data, we conclude that the physiological functions of human Dr1 include regulation of pol III transcription

Design and Stability Analysis of a Super-Twisting Controller for a PS-FBC based Fuel Cell Module

Proton‐exchange membrane fuel cells have been established as a really promising technology, specially due to their high efficiency and scalability features, additionally to their low pollution emissions. In a typical topology, fuel cell module (FCM) is usually integrated into a hybrid power system, where the FCM is designed to satisfy the main power requirements and reduce the current ripple at the fuel cell output. In this framework, the aim of this paper is to analyze and design a sliding mode control (SMC) for a FCM based on an isolated phase‐shifted full bridge converter. This particular topology provides a high conversion ratio and attains a reduction of switching losses, which allow its application in low and medium power systems. From the control viewpoint, the proposed module represents a challenge due to the highly nonlinear behavior and wide operation range of the FCM, together with system parameter uncertainties and perturbations. To solve these issues, a second‐order sliding mode super‐twisting algorithm (STA) is proposed. As its main advantage, the STA reduces significantly the control chattering while preserving several features of conventional SMCs, such as robustness and finite time convergence. In order to analyze the zero dynamics stability, a Lyapunov study is proposed, taking advantage of its particular Liérnad‐type system structure. Finally, the designed algorithm is thoroughly analyzed and validated by computer simulation on a commercial 10‐kW FCM and compared to first‐order SMC.Fil: Anderson Azzano, Jorge Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Moré, Jerónimo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Puleston, Pablo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; Argentin

Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines.

Naïve CD4+ T cells coordinate the immune response by acquiring an effector phenotype in response to cytokines. However, the cytokine responses in memory T cells remain largely understudied. Here we use quantitative proteomics, bulk RNA-seq, and single-cell RNA-seq of over 40,000 human naïve and memory CD4+ T cells to show that responses to cytokines differ substantially between these cell types. Memory T cells are unable to differentiate into the Th2 phenotype, and acquire a Th17-like phenotype in response to iTreg polarization. Single-cell analyses show that T cells constitute a transcriptional continuum that progresses from naïve to central and effector memory T cells, forming an effectorness gradient accompanied by an increase in the expression of chemokines and cytokines. Finally, we show that T cell activation and cytokine responses are influenced by the effectorness gradient. Our results illustrate the heterogeneity of T cell responses, furthering our understanding of inflammation

A diVIsive Shuffling Approach (VIStA) for gene expression analysis to identify subtypes in Chronic Obstructive Pulmonary Disease

Background: An important step toward understanding the biological mechanisms underlying a complex disease is a refined understanding of its clinical heterogeneity. Relating clinical and molecular differences may allow us to define more specific subtypes of patients that respond differently to therapeutic interventions. Results: We developed a novel unbiased method called diVIsive Shuffling Approach (VIStA) that identifies subgroups of patients by maximizing the difference in their gene expression patterns. We tested our algorithm on 140 subjects with Chronic Obstructive Pulmonary Disease (COPD) and found four distinct, biologically and clinically meaningful combinations of clinical characteristics that are associated with large gene expression differences. The dominant characteristic in these combinations was the severity of airflow limitation. Other frequently identified measures included emphysema, fibrinogen levels, phlegm, BMI and age. A pathway analysis of the differentially expressed genes in the identified subtypes suggests that VIStA is capable of capturing specific molecular signatures within in each group. Conclusions: The introduced methodology allowed us to identify combinations of clinical characteristics that correspond to clear gene expression differences. The resulting subtypes for COPD contribute to a better understanding of its heterogeneity

A divisive Shuffling Approach (VIStA) for gene expression analysis to identify subtypes in Chronic Obstructive Pulmonary Disease

An important step toward understanding the biological mechanisms underlying a complex disease is a refined understanding of its clinical heterogeneity. Relating clinical and molecular differences may allow us to define more specific subtypes of patients that respond differently to therapeutic interventions. Results We developed a novel unbiased method called diVIsive Shuffling Approach (VIStA) that identifies subgroups of patients by maximizing the difference in their gene expression patterns. We tested our algorithm on 140 subjects with Chronic Obstructive Pulmonary Disease (COPD) and found four distinct, biologically and clinically meaningful combinations of clinical characteristics that are associated with large gene expression differences. The dominant characteristic in these combinations was the severity of airflow limitation. Other frequently identified measures included emphysema, fibrinogen levels, phlegm, BMI and age. A pathway analysis of the differentially expressed genes in the identified subtypes suggests that VIStA is capable of capturing specific molecular signatures within in each group. Conclusions The introduced methodology allowed us to identify combinations of clinical characteristics that correspond to clear gene expression differences. The resulting subtypes for COPD contribute to a better understanding of its heterogeneity

Prospects of fuel cell combined heat and power systems

Combined heat and power (CHP) in a single and integrated device is concurrent or synchronized production of many sources of usable power, typically electric, as well as thermal. Integrating combined heat and power systems in today's energy market will address energy scarcity, global warming, as well as energy-saving problems. This review highlights the system design for fuel cell CHP technologies. Key among the components discussed was the type of fuel cell stack capable of generating the maximum performance of the entire system. The type of fuel processor used was also noted to influence the systemic performance coupled with its longevity. Other components equally discussed was the power electronics. The thermal and water management was also noted to have an effect on the overall efficiency of the system. Carbon dioxide emission reduction, reduction of electricity cost and grid independence, were some notable advantages associated with fueling cell combined heat and power systems. Despite these merits, the high initial capital cost is a key factor impeding its commercialization. It is, therefore, imperative that future research activities are geared towards the development of novel, and cheap, materials for the development of the fuel cell, which will transcend into a total reduction of the entire system. Similarly, robust, systemic designs should equally be an active research direction. Other types of fuel aside, hydrogen should equally be explored. Proper risk assessment strategies and documentation will similarly expand and accelerate the commercialization of this novel technology. Finally, public sensitization of the technology will also make its acceptance and possible competition with existing forms of energy generation feasible. The work, in summary, showed that proton exchange membrane fuel cell (PEM fuel cell) operated at a lower temperature-oriented cogeneration has good efficiency, and is very reliable. The critical issue pertaining to these systems has to do with the complication associated with water treatment. This implies that the balance of the plant would be significantly affected; likewise, the purity of the gas is crucial in the performance of the system. An alternative to these systems is the PEM fuel cell systems operated at higher temperatures

Bioremoval of marker pen inks by exploiting lipase hydrolysis

[EN] New and eco-sustainable methods based on the catalytic activity of lipases for the removal of acrylic marker pen inks were investigated. Different biocleaning methodologies were tested using lipases from different sources (viz. bacteria and fungi) dispersed in aqueous systems and microemulsions. Blue, green, red and black marker pens were selected for their chemical composition. Unglazed ceramic substrates were painted using marker pens, and some of these samples were subjected to natural and artificial ageing in order to compare the effectiveness of cleaning methods on fresh and aged ink layers. It was evidenced that acrylic polymer-based inks may be removed with an oil in water microemulsion, but cleaning effectiveness was generally enhanced when a lipase was added. Moreover, it was found that all the tests were more effective on the unaged samples, therefore, the cleaning intervention should be performed as soon as possible. Cleaning effectiveness was evaluated by measuring colour differences, acquiring visible reflectance spectra and determining the percentage of white in images of the treated samples by Image J open source software, for the first time used to this purpose. The results illustrate that only a multi-technique approach can correctly evaluate the effectiveness of different cleaning methods. (C) 2017 Elsevier B.V. All rights reserved.The present study was carried out with the support of the following projects: PRIN project no. 2010329WPF "Sustainability in cultural heritage: from diagnosis to the development of innovative systems for consolidation, cleaning and protection", financed by the Italian Ministry of Education, University and Research (MIUR); P.O. PUGLIA ERDF 2007-2013, project code 3Z3VZ46 "II restauro delle grandi opere in Puglia: l'innovazione attraverso le nanotecnologie e metodologie diagnostiche avanzate (RESTAUREO)", financed by Puglia Region (Italy); Potenziamento Strutturale PONa3_00369 of the University "A. Moro" of Bari "Laboratorio per lo Sviluppo Integrato delle Scienze e delle Tecnologie dei Materiali Avanzati e per dispositivi innovativi (SISTEMA)", financed by the MIUR (Italy); Fondo di Sviluppo e Coesione 2007-2013 APQ Ricerca Regione Puglia "Programma regionale a sostegno della specializzazione Intelligente e della sostenibilita sociale ed ambientale - Futureln - Research".Germinario, G.; Van Der Werf, ID.; Palazzo, G.; Regidor Ros, JL.; Montes Estellés, RM.; Sabbatini, L. (2017). Bioremoval of marker pen inks by exploiting lipase hydrolysis. Progress in Organic Coatings. 110:162-171. https://doi.org/10.1016/j.porgcoat.2017.02.019S16217111