An Approach for the Development of Complex Systems Archetypes

The purpose of this research is to explore the principles and concepts of systems theory in pursuit of a collection of complex systems archetypes that can be used for system exploration and diagnostics. The study begins with an examination of the archetypes and classification systems that already exist in the domain of systems theory. This review includes a critique of their purpose, structure, and general applicability. The research then develops and employs a new approach to grounded theory, using a visual coding model to explore the origins, relationships, and meanings of the principles of systems theory. The goal of the visual grounded theory approach is to identity underlying, recurrent imagery in the systems literature that will form the basis for the archetypes. Using coding models derived from the literature, the study then examines the interrelationships between system principles. These relationships are used to clearly define the environment where the archetypes are found in terms of energy, entropy and time. A collection of complex system archetypes is then derived which are firmly rooted in the literature, as well as being demonstrably manifested in the real world. The definitions of the emerging complex systems archetypes are consistent with the environmental definition and are governed by the system’s behavior related to energy collection, entropy displacement, and the pursuit of viability. Once the archetypes have been identified, this study examines the similarities and differences that distinguish them. The individual system principles that either define or differentiate each of the archetypes are described, and real-world manifestations of the archetypes are discussed. The collection of archetypes is then examined as a continuum, where they are related to one another in terms of energy use, entropy accumulation, self-modification and external-modification. To illustrate the applicability of these archetypes, a case study is undertaken which examines a medium-sized organization with multiple departments in an industrial setting. The individual departments are discussed in detail, and their archetypical forms are identified and described. Finally, the study examines future applications for the archetypes and other research that might enhance their utility for complex systems governance

Arterial properties as determinants of left ventricular mass and fibrosis in severe aortic Stenosis : findings from ACRIN PA 4008

Background-The role of arterial load in severe aortic stenosis is increasingly recognized. However, patterns of pulsatile load and their implications in this population are unknown. We aimed to assess the relationship between the arterial properties and both (1) left ventricular remodeling and fibrosis and (2) the clinical course of patients with severe aortic stenosis undergoing aortic valve replacement (AVR). Methods and Results-We enrolled 38 participants with symptomatic severe aortic stenosis scheduled to undergo surgical AVR. Aortic root characteristic impedance, wave reflections parameters (reflection magnitude, reflected wave transit time), and myocardial extracellular mass were measured with cardiac magnetic resonance imaging and arterial tonometry Cardiac magnetic resonance imaging was repeated at 6 months in 30 participants. A reduction in cellular mass (133.6 versus 113.9 g; P=0.002) but not extracellular mass (42.3 versus 40.6 g; P=0.67) was seen after AVR. Participants with higher extracellular mass exhibited greater reflection magnitude (0.68 versus 0.54; P=0.006) and lower aortic root characteristic impedance (56.3 versus 96.9 dynes/s per cm(5); P=0.006). Reflection magnitude was a significant predictor of smaller improvement in the quality of life (Kansas City Cardiomyopathy Questionnaire score) after AVR (R=-0.51; P=0.0026). The 6-minute walk distance at 6 months after AVR was positively correlated with the reflected wave transit time (R=0.52; P=0.01). Conclusions-Consistent with animal studies, arterial wave reflections are associated with interstitial volume expansion in severe aortic stenosis and predict a smaller improvement in quality of life following AVR. Future trials should assess whether wave reflections represent a potential therapeutic target to mitigate myocardial interstitial remodeling and to improve the clinical status of this patient population

Detection of MMP-2 and MMP-9 Activity <i>in Vivo</i> with a Triple-Helical Peptide Optical Probe

We report a novel activatable NIR fluorescent probe for <i>in vivo</i> detection of cancer-related matrix metalloproteinase (MMP) activity. The probe is based on a triple-helical peptide substrate (THP) with high specificity for MMP-2 and MMP-9 relative to other members of the MMP family. MMP-2 and MMP-9 (also known as gelatinases) are specifically associated with cancer cell invasion and cancer-related angiogenesis. At the center of each 5 kDa peptide strand is a gelatinase sensitive sequence flanked by 2 Lys residues conjugated with NIR fluorescent dyes. Upon self-assembly of the triple-helical structure, the 3 peptide chains intertwine, bringing the fluorophores into close proximity and reducing fluorescence via quenching. Upon enzymatic cleavage of the triple-helical peptide, 6 labeled peptide chains are released, resulting in an amplified fluorescent signal. The fluorescence yield of the probe increases 3.8-fold upon activation. Kinetic analysis showed a rate of LS276-THP hydrolysis by MMP-2 (<i>k</i>_cat/<i>K</i>_M = 30,000 s^–1 M^–1) similar to that of MMP-2 catalysis of an analogous fluorogenic THP. Administration of LS276-THP to mice bearing a human fibrosarcoma xenografted tumor resulted in a tumor fluorescence signal more than 5-fold greater than that of muscle. This signal enhancement was reduced by treatment with the MMP inhibitor Ilomostat, indicating that the observed tumor fluorescence was indeed enzyme mediated. These results are the first to demonstrate that triple-helical peptides are suitable for highly specific <i>in vivo</i> detection of tumor-related MMP-2 and MMP-9 activity

Near Infrared Dyes as Lifetime Solvatochromic Probes for Micropolarity Measurements of Biological Systems

The polarity of biological mediums controls a host of physiological processes such as digestion, signaling, transportation, metabolism, and excretion. With the recent widespread use of near-infrared (NIR) fluorescent dyes for biological imaging of cells and living organisms, reporting medium polarity with these dyes would provide invaluable functional information in addition to conventional optical imaging parameters. Here, we report a new approach to determine polarities of macro- and microsystems for in vitro and potential in vivo applications using NIR polymethine molecular probes. Unlike the poor solvatochromic response of NIR dyes in solvents with diverse polarity, their fluorescence lifetimes are highly sensitive, increasing by a factor of up to 8 on moving from polar to nonpolar mediums. We also established a correlation between fluorescence lifetime and solvent orientation polarizability and developed a lifetime polarity index for determining the polarity of complex systems, including micelles and albumin binding sites. Because of the importance of medium polarity in molecular, cellular, and biochemical processes and the significance of reduced autofluorescence and deep tissue penetration of light in the NIR region, the findings reported herein represent an important advance toward using NIR molecular probes to measure the polarity of complex biological systems in vitro and in vivo