Claudia Drummond, Gabriel Coutinho, Marina Carneiro Monteiro, Naima Assuncao, Alina Teldeschi, Andrea Silveira de Souza, Natalia Oliveira, Ivanei Bramati, Felipe Kenji Sudo, Bart Vanderboght, Carlos Otavio Brandao, Rochele Paz Fonseca, Ricardo de Oliveira-Souza, Jorge Moll, Paulo Mattos, Fernanda Tovar-Moll
Background: Narrative discourse (ND) refers to one's ability to verbally reproduce a sequence of temporally and logically-linked events. Impairments in ND may occur in subjects with Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD), but correlates across this function, neuroimaging and cerebrospinal fluid (CSF) AD biomarkers remain understudied.
Objectives: We sought to measure correlates among ND, Diffusion Tensor Imaging (DTI) indexes and AD CSF biomarkers in patients within the AD spectrum.
Results: Groups differed in narrative production (NProd) and comprehension. aMCI and AD presented poorer inference abilities than controls. AD subjects were more impaired than controls and aMCI regarding WB (p<0.01). ROIs DTI assessment distinguished the three groups. Mean Diffusivity (MD) in the uncinate, bilateral parahippocampal cingulate and left inferior occipitofrontal fasciculi negatively correlated with NProd. Changes in specific tracts correlated with T-tau/Aβ1-42 ratio in CSF.
Conclusions: AD and aMCI patients presented more ND impairments than controls. Those findings were associated with changes in ventral language-associated and in the inferior parahippocampal pathways. The latest were correlated with biomarkers' levels in the CSF.
Methods: AD (N=14), aMCI (N=31) and Control (N=39) groups were compared for whole brain (WB) and regions of interest (ROI) DTI parameters, ND and AD CSF biomarkers.
{"title":"Narrative impairment, white matter damage and CSF biomarkers in the Alzheimer's disease spectrum.","authors":"Claudia Drummond, Gabriel Coutinho, Marina Carneiro Monteiro, Naima Assuncao, Alina Teldeschi, Andrea Silveira de Souza, Natalia Oliveira, Ivanei Bramati, Felipe Kenji Sudo, Bart Vanderboght, Carlos Otavio Brandao, Rochele Paz Fonseca, Ricardo de Oliveira-Souza, Jorge Moll, Paulo Mattos, Fernanda Tovar-Moll","doi":"10.18632/aging.102391","DOIUrl":"10.18632/aging.102391","url":null,"abstract":"<p><strong>Background: </strong>Narrative discourse (ND) refers to one's ability to verbally reproduce a sequence of temporally and logically-linked events. Impairments in ND may occur in subjects with Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD), but correlates across this function, neuroimaging and cerebrospinal fluid (CSF) AD biomarkers remain understudied.</p><p><strong>Objectives: </strong>We sought to measure correlates among ND, Diffusion Tensor Imaging (DTI) indexes and AD CSF biomarkers in patients within the AD spectrum.</p><p><strong>Results: </strong>Groups differed in narrative production (NProd) and comprehension. aMCI and AD presented poorer inference abilities than controls. AD subjects were more impaired than controls and aMCI regarding WB (p<0.01). ROIs DTI assessment distinguished the three groups. Mean Diffusivity (MD) in the uncinate, bilateral parahippocampal cingulate and left inferior occipitofrontal fasciculi negatively correlated with NProd. Changes in specific tracts correlated with T-tau/Aβ1-42 ratio in CSF.</p><p><strong>Conclusions: </strong>AD and aMCI patients presented more ND impairments than controls. Those findings were associated with changes in ventral language-associated and in the inferior parahippocampal pathways. The latest were correlated with biomarkers' levels in the CSF.</p><p><strong>Methods: </strong>AD (N=14), aMCI (N=31) and Control (N=39) groups were compared for whole brain (WB) and regions of interest (ROI) DTI parameters, ND and AD CSF biomarkers.</p>","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"2 4","pages":"9188-9208"},"PeriodicalIF":0.0,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72568691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Selective degeneration of dopaminergic neurons, which are predominantly located in the substantia nigra (SN) of the midbrain, is one of the hallmarks of Parkinson's disease (PD). Large-scale microarray experimental data revealed several genes with significantly differential expression between the ventral tegmental area (VTA) and the SN dopamine (DA) neurons. Several epidemiological studies have additionally indicated nicotine-mediated neuroprotection in PD patients. Based on the strong evidence implicating lipoprotein lipase (LPL), pituitary adenylate cyclase-activating polypeptide and gastrin-releasing peptide genes in neuroprotection, this letter investigates areaand age-specific nicotine regulation of these genes' expression in the VTA and SN of different age groups (3 months, 12 months, and 24 months) in an in vivo animal model. Our in vivo rat model results suggest that out of these genes, only the LPL gene has significantly differential expression between the VTA and SN in the senior age group (24 months). Nicotine treatment did not upregulate the neuroprotective genes in adult and senior groups (12 and 24 months). Differential expression of the LPL gene in the senior population may contribute to the different survival rates of DA neurons within the VTA and SN. However, downregulation by nicotine suggests that these genes may not be related to the nicotine-mediated neuroprotection known to reduce the risks of PD. Our results suggest that nicotine may not play an important role in the regulation of neuroprotective gene expressions, while providing new insights into the role of nicotine in PD.
{"title":"The Age-Related Effect of Nicotine on the Expression of Neuroprotective Genes in Ventral Tegmental Area and Substantia Nigra","authors":"Pinar Kanlikilicer;Andrei Dragomir;Die Zhang;Yasemin Akay;Metin Akay","doi":"10.1109/LLS.2017.2756835","DOIUrl":"10.1109/LLS.2017.2756835","url":null,"abstract":"Selective degeneration of dopaminergic neurons, which are predominantly located in the substantia nigra (SN) of the midbrain, is one of the hallmarks of Parkinson's disease (PD). Large-scale microarray experimental data revealed several genes with significantly differential expression between the ventral tegmental area (VTA) and the SN dopamine (DA) neurons. Several epidemiological studies have additionally indicated nicotine-mediated neuroprotection in PD patients. Based on the strong evidence implicating lipoprotein lipase (LPL), pituitary adenylate cyclase-activating polypeptide and gastrin-releasing peptide genes in neuroprotection, this letter investigates areaand age-specific nicotine regulation of these genes' expression in the VTA and SN of different age groups (3 months, 12 months, and 24 months) in an in vivo animal model. Our in vivo rat model results suggest that out of these genes, only the LPL gene has significantly differential expression between the VTA and SN in the senior age group (24 months). Nicotine treatment did not upregulate the neuroprotective genes in adult and senior groups (12 and 24 months). Differential expression of the LPL gene in the senior population may contribute to the different survival rates of DA neurons within the VTA and SN. However, downregulation by nicotine suggests that these genes may not be related to the nicotine-mediated neuroprotection known to reduce the risks of PD. Our results suggest that nicotine may not play an important role in the regulation of neuroprotective gene expressions, while providing new insights into the role of nicotine in PD.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"3 4","pages":"13-16"},"PeriodicalIF":0.0,"publicationDate":"2017-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2017.2756835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41457675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Belousov-Zhabotinsky (BZ) reaction is a complex chemical reaction exhibiting sustained oscillations observed in some real biological oscillators. However, its oscillatory behavior is represented by a simple mechanism, called the Oregonator. Since delay induces unexpected behaviors, the dynamics in BZ reaction in the presence of delays has not been sufficiently addressed. In order to understand the effects induced by the delay parameter in the reaction, by using a two-delay Oregonator-based model, we address the qualitative properties (positivity, boundedness, and stability) of the model in terms of delayed-concentration and delayed-activation. Numerical results are presented to verify the properties of the model described by a qualitative/quantitative analysis.
{"title":"A Delay-Based Sustained Chemical Oscillator: Qualitative Analysis of Oregonator-Based Models","authors":"Hakki Ulaş Ünal;Islam Boussaada;Silviu-Iulian Niculescu","doi":"10.1109/LLS.2017.2756834","DOIUrl":"10.1109/LLS.2017.2756834","url":null,"abstract":"The Belousov-Zhabotinsky (BZ) reaction is a complex chemical reaction exhibiting sustained oscillations observed in some real biological oscillators. However, its oscillatory behavior is represented by a simple mechanism, called the Oregonator. Since delay induces unexpected behaviors, the dynamics in BZ reaction in the presence of delays has not been sufficiently addressed. In order to understand the effects induced by the delay parameter in the reaction, by using a two-delay Oregonator-based model, we address the qualitative properties (positivity, boundedness, and stability) of the model in terms of delayed-concentration and delayed-activation. Numerical results are presented to verify the properties of the model described by a qualitative/quantitative analysis.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"3 3","pages":"9-12"},"PeriodicalIF":0.0,"publicationDate":"2017-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2017.2756834","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48903760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-06-01DOI: 10.1109/LLS.2017.2756886
Jae Hoon Jung;Joseph Szule
Electron tomography can be used to make grayscale volume reconstructions of tissue sections. Images derived from the reconstructions provide the best 3-D spatial resolution currently available for determining the sizes, shapes, and relationships of cellular organelles and macromolecules in situ. Structures of interest are typically examined by segmenting them from the volume and rendering them as surface models according to grayscale values. The fidelity of segmentations and their surface models to the grayscale reconstruction depend on the signal-to-noise ratio (SNR) which can vary considerably between different structures. Current methods of high-fidelity segmentations require tedious manual adjustments. Here, we introduce an automatic optimization method that reduces the manual adjustments, increases the SNR, and improves the fidelity of segmentations and surface models. The method is validated using a well-studied macromolecular assembly in the reconstructions of tissue sections from neuromuscular junctions.
{"title":"Automatic Optimization Method for Segmentation and Surface Model Generation in Electron Tomography","authors":"Jae Hoon Jung;Joseph Szule","doi":"10.1109/LLS.2017.2756886","DOIUrl":"10.1109/LLS.2017.2756886","url":null,"abstract":"Electron tomography can be used to make grayscale volume reconstructions of tissue sections. Images derived from the reconstructions provide the best 3-D spatial resolution currently available for determining the sizes, shapes, and relationships of cellular organelles and macromolecules in situ. Structures of interest are typically examined by segmenting them from the volume and rendering them as surface models according to grayscale values. The fidelity of segmentations and their surface models to the grayscale reconstruction depend on the signal-to-noise ratio (SNR) which can vary considerably between different structures. Current methods of high-fidelity segmentations require tedious manual adjustments. Here, we introduce an automatic optimization method that reduces the manual adjustments, increases the SNR, and improves the fidelity of segmentations and surface models. The method is validated using a well-studied macromolecular assembly in the reconstructions of tissue sections from neuromuscular junctions.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"3 2","pages":"5-8"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2017.2756886","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42320254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-31DOI: 10.1109/LLS.2017.2661981
Andy Koswara;Zoltan K. Nagy
Plug-flow crystallization (PFC) is a promising candidate to realizing the paradigm shift from batch-to-continuous pharmaceutical manufacturing. While PFC has been recently touted as the ideal continuous crystallizer due to its compact design, proper mixing, and flexible cooling and antisolvent control, it is prone to surface fouling or encrustation. In this letter, a model of encrustation growth and dissolution dynamics coupled with PFC is discussed and a novel method of ON-OFF feedback control of PFC with antifouling control is proposed. The study illustrates a quintessential example of quality-by-control concept, which is complementary to the quality-by-design and essential in ensuring desired control performance and product quality.
{"title":"ON–OFF Feedback Control of Plug-Flow Crystallization: A Case of Quality-by-Control in Continuous Manufacturing","authors":"Andy Koswara;Zoltan K. Nagy","doi":"10.1109/LLS.2017.2661981","DOIUrl":"10.1109/LLS.2017.2661981","url":null,"abstract":"Plug-flow crystallization (PFC) is a promising candidate to realizing the paradigm shift from batch-to-continuous pharmaceutical manufacturing. While PFC has been recently touted as the ideal continuous crystallizer due to its compact design, proper mixing, and flexible cooling and antisolvent control, it is prone to surface fouling or encrustation. In this letter, a model of encrustation growth and dissolution dynamics coupled with PFC is discussed and a novel method of ON-OFF feedback control of PFC with antifouling control is proposed. The study illustrates a quintessential example of quality-by-control concept, which is complementary to the quality-by-design and essential in ensuring desired control performance and product quality.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"3 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2017.2661981","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42212614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-29DOI: 10.1109/LLS.2016.2646383
Cesar Augusto Vargas-Garcia;Mohammad Soltani;Abhyudai Singh
How isogenic cell populations maintain size homeostasis, i.e., a narrow distribution of cell size, is an intriguing fundamental problem. We model cell size using a stochastic hybrid system, where a cell grows exponentially in size (volume) over time and probabilistic division events are triggered at discretetime intervals. Moreover, whenever division occurs, size is randomly partitioned among daughter cells. We first consider a scenario where a timer (cell-cycle clock) that measures the time elapsed since the last division event regulates both the cellular growth and division rates. The analysis reveals that such a timer-controlled system cannot achieve size homeostasis, in the sense that the cell-to-cell size variation grows unboundedly with time. To explore biologically meaningful mechanisms for controlling size, we consider two classes of regulation: a size-dependent growth rate and a size-dependent division rate. Our results show that these strategies can provide bounded intercellular variation in cell size and exact mathematical conditions on the form of regulation needed for size homeostasis are derived. Different known forms of size control strategies, such as the adder and the sizer, are shown to be consistent with these results. Finally, we discuss how organisms ranging from bacteria to mammalian cells have adopted different control approaches for maintaining size homeostasis.
{"title":"Conditions for Cell Size Homeostasis: A Stochastic Hybrid System Approach","authors":"Cesar Augusto Vargas-Garcia;Mohammad Soltani;Abhyudai Singh","doi":"10.1109/LLS.2016.2646383","DOIUrl":"https://doi.org/10.1109/LLS.2016.2646383","url":null,"abstract":"How isogenic cell populations maintain size homeostasis, i.e., a narrow distribution of cell size, is an intriguing fundamental problem. We model cell size using a stochastic hybrid system, where a cell grows exponentially in size (volume) over time and probabilistic division events are triggered at discretetime intervals. Moreover, whenever division occurs, size is randomly partitioned among daughter cells. We first consider a scenario where a timer (cell-cycle clock) that measures the time elapsed since the last division event regulates both the cellular growth and division rates. The analysis reveals that such a timer-controlled system cannot achieve size homeostasis, in the sense that the cell-to-cell size variation grows unboundedly with time. To explore biologically meaningful mechanisms for controlling size, we consider two classes of regulation: a size-dependent growth rate and a size-dependent division rate. Our results show that these strategies can provide bounded intercellular variation in cell size and exact mathematical conditions on the form of regulation needed for size homeostasis are derived. Different known forms of size control strategies, such as the adder and the sizer, are shown to be consistent with these results. Finally, we discuss how organisms ranging from bacteria to mammalian cells have adopted different control approaches for maintaining size homeostasis.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"2 4","pages":"47-50"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2016.2646383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49986485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-23DOI: 10.1109/LLS.2016.2644652
Mathias Foo, Jongrae Kim, Jongmin Kim, D. Bates
We consider the design of synthetic embedded feedback circuits that can implement desired changes in the concentration of the output of a biomolecular process (reference tracking in control terminology). Such systems require the use of a “subtractor” to generate an error signal that captures the difference between the current and desired values of the process output. Unfortunately, standard implementations of the subtraction operator using chemical reaction networks are one sided, i.e., they cannot produce negative error signals. Previous attempts to deal with this problem by representing signals as the difference in concentrations of two different biomolecular species lead to a doubling of the number of chemical reactions required to generate the circuit, hence sharply increasing the difficulty of experimental implementations and limiting the complexity of potential designs. Here, we propose an alternative approach that introduces a degradation term into the classical proportion–integral (PI) control scheme. The extra tuning flexibility of the PI degradation controller compensates for the limitations of the one-sided subtraction operator, providing robust high-performance tracking of concentration changes with a minimal number of chemical reactions.
{"title":"Proportional–Integral Degradation Control Allows Accurate Tracking of Biomolecular Concentrations With Fewer Chemical Reactions","authors":"Mathias Foo, Jongrae Kim, Jongmin Kim, D. Bates","doi":"10.1109/LLS.2016.2644652","DOIUrl":"https://doi.org/10.1109/LLS.2016.2644652","url":null,"abstract":"We consider the design of synthetic embedded feedback circuits that can implement desired changes in the concentration of the output of a biomolecular process (reference tracking in control terminology). Such systems require the use of a “subtractor” to generate an error signal that captures the difference between the current and desired values of the process output. Unfortunately, standard implementations of the subtraction operator using chemical reaction networks are one sided, i.e., they cannot produce negative error signals. Previous attempts to deal with this problem by representing signals as the difference in concentrations of two different biomolecular species lead to a doubling of the number of chemical reactions required to generate the circuit, hence sharply increasing the difficulty of experimental implementations and limiting the complexity of potential designs. Here, we propose an alternative approach that introduces a degradation term into the classical proportion–integral (PI) control scheme. The extra tuning flexibility of the PI degradation controller compensates for the limitations of the one-sided subtraction operator, providing robust high-performance tracking of concentration changes with a minimal number of chemical reactions.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"2 1","pages":"55-58"},"PeriodicalIF":0.0,"publicationDate":"2016-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2016.2644652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62509668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-23DOI: 10.1109/LLS.2016.2644649
Michael Vilkhovoy;Mason Minot;Jeffrey D. Varner
Mathematical models of biochemical networks are the useful tools to understand and ultimately predict how cells utilize nutrients to produce valuable products. Hybrid cybernetic models (HCMs) in combination with elementary modes (EMs) are a tool to model cellular metabolism. However, HCM is limited to reduced metabolic networks because of the computational burden of calculating EMs. In this letter, we develop the hybrid cybernetic modeling with flux balance analysis (HCM-FBA) technique, which uses flux balance solutions instead of EMs to dynamically model metabolism. We show that HCM-FBA has comparable performance to HCM for a proof of concept metabolic network and for a reduced anaerobic E. coli network. Next, HCM-FBA is applied to a larger metabolic network of aerobic E. coli metabolism, which was infeasible for HCM (29 FBA modes versus more than 153 000 EMs). The global sensitivity analysis further reduces the number of FBA modes required to describe the aerobic E. coli data, while maintaining model fit. Thus, HCM-FBA is a promising alternative to HCM for large networks, where the generation of EMs is infeasible.
{"title":"Effective Dynamic Models of Metabolic Networks","authors":"Michael Vilkhovoy;Mason Minot;Jeffrey D. Varner","doi":"10.1109/LLS.2016.2644649","DOIUrl":"https://doi.org/10.1109/LLS.2016.2644649","url":null,"abstract":"Mathematical models of biochemical networks are the useful tools to understand and ultimately predict how cells utilize nutrients to produce valuable products. Hybrid cybernetic models (HCMs) in combination with elementary modes (EMs) are a tool to model cellular metabolism. However, HCM is limited to reduced metabolic networks because of the computational burden of calculating EMs. In this letter, we develop the hybrid cybernetic modeling with flux balance analysis (HCM-FBA) technique, which uses flux balance solutions instead of EMs to dynamically model metabolism. We show that HCM-FBA has comparable performance to HCM for a proof of concept metabolic network and for a reduced anaerobic E. coli network. Next, HCM-FBA is applied to a larger metabolic network of aerobic E. coli metabolism, which was infeasible for HCM (29 FBA modes versus more than 153 000 EMs). The global sensitivity analysis further reduces the number of FBA modes required to describe the aerobic E. coli data, while maintaining model fit. Thus, HCM-FBA is a promising alternative to HCM for large networks, where the generation of EMs is infeasible.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"2 4","pages":"51-54"},"PeriodicalIF":0.0,"publicationDate":"2016-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2016.2644649","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49986486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-23DOI: 10.1109/LLS.2016.2644652
Mathias Foo;Jongrae Kim;Jongmin Kim;Declan G. Bates
We consider the design of synthetic embedded feedback circuits that can implement desired changes in the concentration of the output of a biomolecular process ( reference tracking in control terminology). Such systems require the use of a “subtractor” to generate an error signal that captures the difference between the current and desired values of the process output. Unfortunately, standard implementations of the subtraction operator using chemical reaction networks are one sided, i.e., they cannot produce negative error signals. Previous attempts to deal with this problem by representing signals as the difference in concentrations of two different biomolecular species lead to a doubling of the number of chemical reactions required to generate the circuit, hence sharply increasing the difficulty of experimental implementations and limiting the complexity of potential designs. Here, we propose an alternative approach that introduces a degradation term into the classical proportion–integral (PI) control scheme. The extra tuning flexibility of the PI degradation controller compensates for the limitations of the one-sided subtraction operator, providing robust high-performance tracking of concentration changes with a minimal number of chemical reactions.
{"title":"Proportional–Integral Degradation Control Allows Accurate Tracking of Biomolecular Concentrations With Fewer Chemical Reactions","authors":"Mathias Foo;Jongrae Kim;Jongmin Kim;Declan G. Bates","doi":"10.1109/LLS.2016.2644652","DOIUrl":"https://doi.org/10.1109/LLS.2016.2644652","url":null,"abstract":"We consider the design of synthetic embedded feedback circuits that can implement desired changes in the concentration of the output of a biomolecular process (\u0000<italic>reference tracking</i>\u0000 in control terminology). Such systems require the use of a “subtractor” to generate an error signal that captures the difference between the current and desired values of the process output. Unfortunately, standard implementations of the subtraction operator using chemical reaction networks are one sided, i.e., they cannot produce negative error signals. Previous attempts to deal with this problem by representing signals as the difference in concentrations of two different biomolecular species lead to a doubling of the number of chemical reactions required to generate the circuit, hence sharply increasing the difficulty of experimental implementations and limiting the complexity of potential designs. Here, we propose an alternative approach that introduces a degradation term into the classical proportion–integral (PI) control scheme. The extra tuning flexibility of the PI degradation controller compensates for the limitations of the one-sided subtraction operator, providing robust high-performance tracking of concentration changes with a minimal number of chemical reactions.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"2 4","pages":"55-58"},"PeriodicalIF":0.0,"publicationDate":"2016-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2016.2644652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49986487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-23DOI: 10.1109/LLS.2016.2644648
L. Castelli, R. Pesenti, D. Segrè
Each living cell needs to solve a resource allocation problem, in which multiple inputs (uptake fluxes) and outputs (secretion fluxes) are the outcome of the stoichiometry of biochemical pathways and the regulation of metabolic enzymes. Quantifying the efficiency with which a cell solves this resource allocation problem constitutes a basic question in “cellular economics.” In this letter, we propose the use of data envelopment analysis (DEA) to define multidimensional yields that can capture the multidimensional nature of cell input–output processes. The DEA, by treating cells as decision-making units, enables one to introduce the concept of efficiency frontier that is both intimately connected to the shadow prices of flux balance analysis and useful to estimate the phenotypic phase space from experimental measurements of fluxes.
{"title":"The Cell as a Decision-Making Unit","authors":"L. Castelli, R. Pesenti, D. Segrè","doi":"10.1109/LLS.2016.2644648","DOIUrl":"https://doi.org/10.1109/LLS.2016.2644648","url":null,"abstract":"Each living cell needs to solve a resource allocation problem, in which multiple inputs (uptake fluxes) and outputs (secretion fluxes) are the outcome of the stoichiometry of biochemical pathways and the regulation of metabolic enzymes. Quantifying the efficiency with which a cell solves this resource allocation problem constitutes a basic question in “cellular economics.” In this letter, we propose the use of data envelopment analysis (DEA) to define multidimensional yields that can capture the multidimensional nature of cell input–output processes. The DEA, by treating cells as decision-making units, enables one to introduce the concept of efficiency frontier that is both intimately connected to the shadow prices of flux balance analysis and useful to estimate the phenotypic phase space from experimental measurements of fluxes.","PeriodicalId":87271,"journal":{"name":"IEEE life sciences letters","volume":"2 1","pages":"27-30"},"PeriodicalIF":0.0,"publicationDate":"2016-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1109/LLS.2016.2644648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62509628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号