Mapping behavioral specifications to model parameters in synthetic biology

With recent improvements of protocols for the assembly of transcriptional parts, synthetic biological devices can now more reliably be assembled according to a given design. The standardization of parts open up the way for in silico design tools that improve the construct and optimize devices with respect to given formal design specifications. The simplest such optimization is the selection of kinetic parameters and protein abundances such that the specified design constraints are robustly satisfied. In this work we address the problem of determining parameter values that fulfill specifications expressed in terms of a functional on the trajectories of a dynamical model. We solve this inverse problem by linearizing the forward operator that maps parameter sets to specifications, and then inverting it locally. This approach has two advantages over brute-force random sampling. First, the linearization approach allows us to map back intervals instead of points and second, every obtained value in the parameter region is satisfying the specifications by construction. The method is general and can hence be incorporated in a pipeline for the rational forward design of arbitrary devices in synthetic biology

Supplemental Material, Web_Appendix - Understanding Consumer Dynamic Decision Making Under Competing Loyalty Programs

Supplemental Material, Web_Appendix for Understanding Consumer Dynamic Decision Making Under Competing Loyalty Programs by Jia Liu and Asim Ansari in Journal of Marketing Research</p

Additional file 1 of Lysophosphatidic acid is associated with oocyte maturation by enhancing autophagy via PI3K-AKT-mTOR signaling pathway in granulosa cells

Additional file 1

sj-pdf-1-mrj-10.1177_00222437221134237 - Supplemental material for The Daily Me Versus the Daily Others: How Do Recommendation Algorithms Change User Interests? Evidence from a Knowledge-Sharing Platform

Supplemental material, sj-pdf-1-mrj-10.1177_00222437221134237 for The Daily Me Versus the Daily Others: How Do Recommendation Algorithms Change User Interests? Evidence from a Knowledge-Sharing Platform by Jia Liu and Ziwei Cong in Journal of Marketing Research</p

Synthesis of the C11−C23 Fragment of Spirastrellolide A. A Ketal-Tethered RCM Approach to the Construction of Spiroketals

The synthesis of the C11−C23 fragment in spirastrellolide A is described here featuring a ketal-tethered RCM as an alternative approach to the construction of spiroketals

Synthesis of the C11−C23 Fragment of Spirastrellolide A. A Ketal-Tethered RCM Approach to the Construction of Spiroketals

The synthesis of the C11−C23 fragment in spirastrellolide A is described here featuring a ketal-tethered RCM as an alternative approach to the construction of spiroketals

Liraglutide and Exercise Synergistically Attenuate Vascular Inflammation and Enhance Metabolic Insulin Action in Early Diet-induced Obesity

   Inflammation-induced vascular insulin resistance is an early event in diet-induced obesity and contributes to metabolic insulin resistance. To examine whether exercise and glucagon-like peptide 1 (GLP-1) receptor agonism, alone or in combination, modulate vascular and metabolic insulin actions during obesity development, we performed a euglycemic insulin clamp in adult male rats after 2 weeks of high-fat diet feeding with either access to running wheel (exercise), liraglutide, or both. Rats exhibited increased visceral adiposity and blunted microvascular and metabolic insulin responses. Exercise and liraglutide alone each improved muscle insulin sensitivity but their combination fully restored insulin-mediated glucose infusion rates. The combined exercise and liraglutide intervention enhanced insulin-mediated muscle microvascular perfusion, reduced perivascular macrophage accumulation and superoxide production in the muscle, attenuated blood vessel inflammation and improved endothelial function, along with increased endothelial nucleus translocation of NRF2 and increased endothelial AMPK phosphorylation. We conclude that exercise and liraglutide synergistically enhance the metabolic actions of insulin and reduce vascular oxidative stress and inflammation in the early stage of obesity development. Our data suggest that early combination use of exercise and GLP-1 receptor agonism might be an effective strategy in preventing vascular and metabolic insulin resistance and associated complications during the development of obesity.</p

Histograms showing concentrations of OHCbl and CNCbl in PTZ-induced kindling rat model and controls (n = 8).

Each bar represents the mean value; variability is shown by standard error of mean (SEM). Asterisks represent significant difference.</p

Purification, cDNA cloning and characterization of Kunitz-type protease inhibitors from <i>Apios americana</i> tubers

Two kinds of Kunitz-type protease inhibitors, AKPI1 and AKPI2, were purified from Apios americana tubers by four steps of column chromatographies and their cDNA cloning was performed. AKPI1 cDNA consist of 809 nucleotides, and the matured protein had 190 amino acids with 20,594 Da. AKPI2 cDNA consist of 794 nucleotides, and the matured protein had 177 amino acids with 19,336 Da. P1 site of AKPI2 was Leu88, suggested the target enzyme was chymotrypsin. On the other hand, Gly85-Ile86-Ser87 was positioned around P1 site of AKTI1. Sequence analysis suggested that two forms (single-chain and two-chain form) of AKPI2 protein were present in the tubers. Recombinant AKPI2 expressed by E.coli system showed inhibitory activity toward serine proteases and heat stability. The Ki values toward chymotrypsin and trypsin were 4 × 10−7 M and 6 × 10−6 M, respectively. Abbreviations: AAL: Apios americana lectin; AATI: Apios americana Bowman-Birk type trypsin inhibitor; ACE: angiotensin-converting enzyme; IPTG: isopropyl-β-D-thio-galactopyranoside; Ki: inhibition constant; KPIs: Kunitz-type protease inhibitors; L-BAPA: Benzoyl-L-arginine p-nitroanilide monohydrochloride; L-BTPA: Benzoyl-L-tyrosine p-nitroanilide; PFLNA: Pyr-Phe-Leu-p-nitroanilide; RP-HPLC: reverse-phase high-performance liquid chromatography; RT-PCR: reverse transcription-polymerase chain reaction; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SLIC: sequence and ligation independent cloning; STANA: N-Succinyl-Ala-Ala-Ala-p-nitroanilide; SHR: spontaneously hypertensive rats; TFA: trifluoroacetic acid; UTR: untranslated region. Kunitz-type trypsin inhibitors AKPI1 and AKPI2 were purified and the cDNA cloning and functional expression were performed.</p

The online SPE-HPLC-MS/MS gradient elution and valve switching program.

The online SPE-HPLC-MS/MS gradient elution and valve switching program.</p