Parallel Control of an Artificial Pancreas with Coordinated Insulin, Glucagon, and Rescue Carbohydrate Control Actions

Background: An artificial pancreas with insulin and glucagon delivery has the potential to reduce the risk of hypo- and hyperglycemia in people with type 1 diabetes. However, a maximum dose of glucagon of 1 mg/d is recommended, potentially still requiring rescue carbohydrates in some situations. This work presents a parallel control structure with intrinsic insulin, glucagon, and rescue carbohydrates coordination to overcome glucagon limitations when needed. Methods: The coordinated controller that combines insulin, glucagon, and rescue carbohydrate suggestions (DH-CC-CHO) was compared with the insulin and glucagon delivery coordinated controller (DH-CC). The impact of carbohydrate quantization for practical delivery was also assessed. An in silico study using the UVA-Padova simulator, extended to include exercise and various sources of variability, was performed. Results: DH-CC and DH-CC-CHO performed similarly with regard to mean glucose (126.25 [123.43; 130.73] vs 127.92 [123.99; 132.97] mg/dL, P = .088), time in range (93.04 [90.00; 95.92] vs 92.91 [90.05; 95.75]%, P = .508), time above 180 mg/dL (4.94 [2.72; 7.53] vs 4.99 [2.93; 7.24]%, P = .966), time below 70 mg/dL (0.61 [0.09; 1.75] vs 0.96 [0.23; 2.17]%, P = .1364), insulin delivery (43.50 [38.68; 51.75] vs 42.86 [38.58; 51.36] U/d, P = .383), and glucagon delivery (0.75 [0.40; 1.83] vs 0.76 [0.43; 0.99] mg/d, P = .407). Time below 54 mg/dL was different (0.00 [0.00; 0.05] vs 0.00 [0.00; 0.16]%, P = .036), although non-clinically significant. This was due to the carbs quantization effect in a specific patient, as no statistical difference was found when carbs were not quantized (0.00 [0.00; 0.05] vs 0.00 [0.00; 0.00]%, P = .265). Conclusions: The new strategy of automatic rescue carbohydrates suggestion in coordination with insulin and glucagon delivery to overcome constraints on daily glucagon delivery was successfully evaluated in an in silico proof of concept.

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Insight into the impact of EGFR L792Y/F/H mutations on sensitivity to osimertinib: an in silico study

New Journal of Chemistry ◽

10.1039/d0nj05570k ◽

2021 ◽

Vol 45 (10) ◽

pp. 4756-4765

Author(s):

Daoxing Chen ◽

Liting Zhang ◽

Yanan Liu ◽

Jiali Song ◽

Jingwen Guo ◽

...

Keyword(s):

In Silico ◽

In Silico Study ◽

The Impact ◽

Insight Into

EGFR L792Y/F/H mutation makes it difficult for Osimertinib to recognize ATP pockets.

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New strategy for identifying potential natural HIV-1 non-nucleoside reverse transcriptase inhibitors against drug-resistance: an in silico study

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2019.1656673 ◽

2019 ◽

Vol 38 (11) ◽

pp. 3327-3341 ◽

Cited By ~ 5

Author(s):

Yanjing Wang ◽

Xiangeng Wang ◽

Yi Xiong ◽

Aman Chandra Kaushik ◽

Junaid Muhammad ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

In Silico ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

In Silico Study ◽

New Strategy ◽

Hiv 1

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The Comparison Between the Mutated HuIFN-β 27-101 and the WildType Interferon β: the Comprehensive In Silico Study to Evaluate theEffect of Mutations on IFN-β

Advanced Pharmaceutical Bulletin ◽

10.15171/apb.2019.074 ◽

2019 ◽

Vol 9 (4) ◽

pp. 640-648

Author(s):

Sayed Sharif Balkhi ◽

Zohreh Hojati

Keyword(s):

Molecular Docking ◽

In Silico ◽

Interferon Beta ◽

Human Interferon ◽

Meaningful Relationship ◽

Significant Difference ◽

In Silico Study ◽

The Impact ◽

Life Function

Purpose: Interferon beta (IFN-β) is used to combat multiple sclerosis (MS) disease. CreatingR27T and V101F mutations (mHuIFN-β-27 and mHuIFN-β-101) is one of the tasks performedto improve human interferon beta (HuIFN-β) half-life, function and expression. In this work,the impact of R27T and V101F mutations in recombinant IFN-β on its binding to interferonreceptors were studied by molecular docking.Methods: This work was performed through in silico study. The simulation of mutation wasperformed using the online Rosetta Backrub software and checked using server verify3D.Comparison of access to the solvent of the amino acids in the structures created was performedusing the asaview online server. Also, the effect of mutations on the fold of the protein wasreviewed by the online HOPE server. The molecular docking was performed between HuIFN-βand the external region of IFNAR receptor using the online ClusPro2 protein-protein dockingserver.Results: The comparison of the values of the negative binding energy (ΔGbind) obtained fromprotein-protein molecular docking between IFNAR receptor and HuIFN-β, mHuIFN-β-27,mHuIFN-β-101 and mHuIFN-β-27-101 ligands did not show a significant difference, and thesedifferences do not see any meaningful relationship between them (P > 0.9999).Conclusion: Regarding these results, it can be concluded that these mutations do not have anegative effect on the composition of the complex rHuIFN-β/IFNAR. So, they do not interferewith the binding of the IFN-β to the receptor. It is concluded that the quality of the rHuIFN-β isimproved by introducing these two mutations.<br />

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In silico evaluation of a Parallel Control-based Coordinated Dual-Hormone Artificial Pancreas with Insulin on Board Limitation

2019 American Control Conference (ACC) ◽

10.23919/acc.2019.8815023 ◽

2019 ◽

Cited By ~ 1

Author(s):

V. Moscardo ◽

P. Herrero ◽

J. L. Diez ◽

M. Gimenez ◽

P. Rossetti ◽

...

Keyword(s):

In Silico ◽

Artificial Pancreas ◽

Parallel Control

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Therapeutic Potential of Tuna Backbone Peptide and Its Analogs: An In Vitro and In Silico Study

Molecules ◽

10.3390/molecules26072064 ◽

2021 ◽

Vol 26 (7) ◽

pp. 2064

Author(s):

Varun Gopinatth ◽

Rufa L. Mendez ◽

Elaine Ballinger ◽

Jung Yeon Kwon

Keyword(s):

In Silico ◽

Bioactive Peptides ◽

Therapeutic Potential ◽

Antioxidant Activities ◽

Radical Scavenging ◽

Activity Assay ◽

In Silico Study ◽

The Impact ◽

Potent Inhibitory Activity

Tuna backbone peptide (TBP) has been reported to exert potent inhibitory activity against lipid peroxidation in vitro. Since this bears relevant physiological implications, this study was undertaken to assess the impact of peptide modifications on its bioactivity and other therapeutic potential using in vitro and in silico approach. Some TBP analogs, despite lower purity than the parent peptide, exerted promising antioxidant activities in vitro demonstrated by ABTS radical scavenging assay and cellular antioxidant activity assay. In silico digestion of the peptides resulted in the generation of antioxidant, angiotensin-converting enzyme (ACE), and dipeptidyl peptidase-IV (DPPIV) inhibitory dipeptides. Using bioinformatics platforms, we found five stable TBP analogs that hold therapeutic potential with their predicted multifunctionality, stability, non-toxicity, and low bitterness intensity. This work shows how screening and prospecting for bioactive peptides can be improved with the use of in vitro and in silico approaches.

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