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

Development of a fluorescence based viscosity sensor for medical applications

Abstract only availableThe purpose of this project is to determine the binding properties of molecular rotors with macromolecules, specifically plasma proteins. This is to aid in the development of a viscometer based on molecular rotors that could be used on blood plasma by determining to what effect the presence of these proteins will affect the measurements of the viscometer so that it may be put into use in the medical field. Molecular rotors are a class of florescent molecules that form a twisted internal charge transfer complex upon excitation, they have a preferred de-excitation pathway of rotation about a C=C double bond. When molecular free volume is limited, rotation about this bond is hindered and fluorescence probability increases. The intensity of the fluorescence of these molecules can be used as a measure of the viscosity of the solvent. Intensity and viscosity are related by the following equation: log F = C + x log h where F is the fluorescent yield, h is the viscosity, and x and C are constants. The rotors in this study are CCVJ (9-[(2-Cyano-2-hydroxy carbonal) vinyl] julolidine) and CCVJ-TEG (9-[(2-Cyano-2-hydroxy carbonal) vinyl] julolidine triethyleneglycol). The affinity of these molecular rotors to various plasma proteins is determined by comparing the solubility of the molecular rotors in proteinaceous and nonproteinaceous solutions. The molecular rotors are allowed to diffuse through a dialysis membrane until the equilibrium between the two solutions is reached. The concentration of the rotors in the solutions was determined by measuring the absorbance of these solutions according to the Beer-Lambert law: A= e * c where A is absorbance, e is the extinction coefficient of the specific substance at the specific wavelength, and c is the concentration of that substance. The proteins tested in this manner were albumin, fibrinogen, and IgG. Bovine proteins were used because all mammalian proteins are very similar and bovine proteins are easier to obtain than human proteins. The results show that CCVJ and CCVJ-TEG are very strongly attracted to Albumin, and weakly attracted to fibrinogen. This attraction may affect the fluorescence of the rotor molecules, meaning that in developing these molecular rotors as viscosity sensors for blood plasma, further studies must be performed to determine the effect of the proteins on the fluorescent behavior of the rotors so that the protein composition of the plasma can be accounted for.Life Sciences Undergraduate Research Opportunity Progra

Noninvasive imaging of focal atherosclerotic lesions using fluorescence molecular tomography

Insights into the etiology of stroke and myocardial infarction suggest that rupture of unstable atherosclerotic plaque is the precipitating event. Clinicians lack tools to detect lesion instability early enough to intervene, and are often left to manage patients empirically, or worse, after plaque rupture. Noninvasive imaging of the molecular events signaling prerupture plaque progression has the potential to reduce the morbidity and mortality associated with myocardial infarction and stroke by allowing early intervention. Here, we demonstrate proof-of-principle in vivo molecular imaging of C-type natriuretic peptide receptor in focal atherosclerotic lesions in the femoral arteries of New Zealand white rabbits using a custom built fiber-based, fluorescence molecular tomography (FMT) system. Longitudinal imaging showed changes in the fluorescence signal intensity as the plaque progressed in the air-desiccated vessel compared to the uninjured vessel, which was validated by ex vivo tissue studies. In summary, we demonstrate the potential of FMT for noninvasive detection of molecular events leading to unstable lesions heralding plaque rupture

Multimodal sentinel lymph node mapping with single-photon emission computed tomography (SPECT)/computed tomography (CT) and photoacoustic tomography

The identification of cancer cells in the lymph nodes surrounding a tumor is important in establishing a prognosis. Optical detection techniques such as fluorescence and photoacoustic tomography (PAT) have been reported in preclinical studies for noninvasive sentinel lymph node (SLN) mapping. A method for validation of these techniques is needed for clinical trials. We report the use of a multimodal optical-radionuclear contrast agent as a validation tool for PAT in a preclinical model. Methylene blue (MB) was radiolabeled with ^(125)I for multimodal SLN mapping and used in conjunction with MB to assess the feasibility of multimodal SLN mapping in a rat model by PAT and single-photon emission computed tomography (SPECT). MB provided sufficient contrast for identifying SLNs noninvasively with a PAT system adapted from a clinical ultrasound imaging system. The signal location was corroborated by SPECT using ^(125)I labeled MB. The translation of PAT into the clinic can be facilitated by a direct comparison with established imaging methods using a clinically relevant dual SPECT and photoacoustic imaging agent. The new high-resolution PAT is a promising technology for the sensitive and accurate SLN detection in cancer patients

Isosorbide dinitrate, with or without hydralazine, does not reduce wave reflections, left ventricular hypertrophy, or myocardial fibrosis in patients with heart failure with preserved ejection fraction

Background-Wave reflections, which are increased in patients with heart failure with preserved ejection fraction, impair diastolic function and promote pathologic myocardial remodeling. Organic nitrates reduce wave reflections acutely, but whether this is sustained chronically or affected by hydralazine coadministration is unknown. Methods and Results-We randomized 44 patients with heart failure with preserved ejection fraction in a double-blinded fashion to isosorbide dinitrate (ISDN; n=13), ISDN+hydralazine (ISDN+hydral; n=15), or placebo (n=16) for 6months. The primary end point was the change in reflection magnitude (RM; assessed with arterial tonometry and Doppler echocardiography). Secondary end points included change in left ventricular mass and fibrosis, measured with cardiac magnetic resonance imaging, and the 6-minute walk distance. ISDN reduced aortic characteristic impedance (mean baseline=0.15 [95% CI, 0.14-0.17], 3 months=0.11 [95% CI, 0.10-0.13], 6 months=0.10 [95% CI, 0.08-0.12] mmHg/mL per second; P=0.003) and forward wave amplitude (P-f, mean baseline=54.8 [95% CI, 47.6-62.0], 3 months=42.2 [95% CI, 33.2-51.3]; 6 months=37.0 [95% CI, 27.2-46.8] mmHg, P=0.04), but had no effect on RM (P=0.64), left ventricular mass (P=0.33), or fibrosis (P=0.63). ISDN+hydral increased RM (mean baseline=0.39 [95% CI, 0.35-0.43]; 3 months=0.31 [95% CI, 0.25-0.36]; 6 months=0.44 [95% CI, 0.37-0.51], P=0.03), reduced 6-minute walk distance (mean baseline=343.3 [95% CI, 319.2-367.4]; 6 months=277.0 [95% CI, 242.7-311.4] meters, P=0.022), and increased native myocardial T1 (mean baseline=1016.2 [95% CI, 1002.7-1029.7]; 6 months=1054.5 [95% CI, 1036.5-1072.3], P=0.021). A high proportion of patients experienced adverse events with active therapy (ISDN=61.5%, ISDN+hydral=60.0%; placebo=12.5%; P=0.007). Conclusions-ISDN, with or without hydralazine, does not exert beneficial effects on RM, left ventricular remodeling, or submaximal exercise and is poorly tolerated. ISDN+hydral appears to have deleterious effects on RM, myocardial remodeling, and submaximal exercise. Our findings do not support the routine use of these vasodilators in patients with heart failure with preserved ejection fraction

Video-rate fluorescence diffuse optical tomography for in vivo sentinel lymph node imaging

We have developed a fiber-based, video-rate fluorescence diffuse optical tomography (DOT) system for noninvasive in vivo sentinel lymph node (SLN) mapping. Concurrent acquisition of fluorescence and reference signals allowed the efficient generation of ratio-metric data for 3D image reconstruction. Accurate depth localization and high sensitivity to fluorescent targets were established in to depths of >10 mm. In vivo accumulation of indocyanine green (ICG) dye was imaged in the region of the SLN following intradermal injection into the forepaw of rats. These results suggest that video-rate fluorescence DOT has significant potential as a clinical tool for noninvasive mapping of SLN

Disjoint Hamilton cycles in transposition graphs

This paper was accepted for publication in the journal Discrete Applied Mathematics and the definitive published version is available at http://dx.doi.org/10.1016/j.dam.2016.02.007.Most network topologies that have been studied have been subgraphs of transposition graphs. Edge-disjoint Hamilton cycles are important in network topologies for improving fault-tolerance and distribution of messaging traffic over the network. Not much was known about edge-disjoint Hamilton cycles in general transposition graphs until recently Hung produced a construction of 4 edge-disjoint Hamilton cycles in the 5-dimensional transposition graph and showed how edge-disjoint Hamilton cycles in (n + 1)-dimensional transposition graphs can be constructed inductively from edge-disjoint Hamilton cycles in n-dimensional transposition graphs. In the same work it was conjectured that n-dimensional transposition graphs have n − 1 edge-disjoint Hamilton cycles for all n greater than or equal to 5. In this paper we provide an edge-labelling for transposition graphs and, by considering known Hamilton cycles in labelled star subgraphs of transposition graphs, are able to provide an extra edge-disjoint Hamilton cycle at the inductive step from dimension n to n + 1, and thereby prove the conjecture

Noninvasive Photoacoustic and Fluorescence Sentinel Lymph Node Identification using Dye-Loaded Perfluorocarbon Nanoparticles

The contrast mechanisms used for photoacoustic tomography (PAT) and fluorescence imaging differ in subtle, but significant, ways. The design of contrast agents for each or both modalities requires an understanding of the spectral characteristics as well as intra- and intermolecular interactions that occur during formulation. We found that fluorescence quenching that occurs in the formulation of near-infrared (NIR) fluorescent dyes in nanoparticles results in enhanced contrast for PAT. The ability of the new PAT method to utilize strongly absorbing chromophores for signal generation allowed us to convert a highly fluorescent dye into an exceptionally high PA contrast material. Spectroscopic characterization of the developed NIR dye-loaded perfluorocarbon-based nanoparticles for combined fluorescence and PA imaging revealed distinct dye-dependent photophysical behavior. We demonstrate that the enhanced contrast allows detection of regional lymph nodes of rats in vivo with time-domain optical and photoacoustic imaging methods. The results further show that the use of fluorescence lifetime imaging, which is less dependent on fluorescence intensity, provides a strategic approach to bridge the disparate contrast reporting mechanisms of fluorescence and PA imaging methods