Cupolets in a chaotic neuron model.

This paper reports the first finding of cupolets in a chaotic Hindmarsh-Rose neural model. Cupolets (chaotic, unstable, periodic, orbit-lets) are unstable periodic orbits that have been stabilized through a particular control scheme by applying a binary control sequence. We demonstrate different neural dynamics (periodic or chaotic) of the Hindmarsh-Rose model through a bifurcation diagram where the external input current, I, is the bifurcation parameter. We select a region in the chaotic parameter space and provide the results of numerical simulations. In this chosen parameter space, a control scheme is applied when the trajectory intersects with either of the two control planes. The type of the control is determined by a bit in a binary control sequence. The control is either a small microcontrol (0) or a large macrocontrol (1) that adjusts the future dynamics of the trajectory by a perturbation determined by the coding function r ( x ). We report the discovery of many cupolets with corresponding control sequences and comment on the differences with previously reported cupolets in the double scroll system. We provide some examples of the generated cupolets and conclude by discussing potential implications for biological neurons.

Chaotic Entanglement: Entropy and Geometry.

In chaotic entanglement, pairs of interacting classically-chaotic systems are induced into a state of mutual stabilization that can be maintained without external controls and that exhibits several properties consistent with quantum entanglement. In such a state, the chaotic behavior of each system is stabilized onto one of the system's many unstable periodic orbits (generally located densely on the associated attractor), and the ensuing periodicity of each system is sustained by the symbolic dynamics of its partner system, and vice versa. Notably, chaotic entanglement is an entropy-reversing event: the entropy of each member of an entangled pair decreases to zero when each system collapses onto a given period orbit. In this paper, we discuss the role that entropy plays in chaotic entanglement. We also describe the geometry that arises when pairs of entangled chaotic systems organize into coherent structures that range in complexity from simple tripartite lattices to more involved patterns. We conclude with a discussion of future research directions.

A pilot study of the effects of a high-intensity aerobic exercise session on heart rate variability and arterial compliance in adolescents with or without type 1 diabetes.

Arterial compliance and autonomic regulation are predictors of cardiovascular disease. In adults, both are altered chronically by type 1 diabetes (T1D) and acutely by exercise; however, the effects of T1D and exercise are less clear in adolescents. We measured short-term effects of a high-intensity aerobic interval exercise session on cardiovascular and metabolic variables in normal weight adolescents with T1D or without T1D (Control). Energy expenditure (EE), heart rate variability (HRV), arterial compliance, and blood pressure (BP) were measured before exercise (baseline) and three times over 105 minutes postexercise. The T1D and control groups had similar cardiorespiratory fitness and accelerometer-measured physical activity. The T1D group had higher EE and fat oxidation throughout the trial, but postexercise changes were similar between groups. HRV transiently declined following exercise in both groups, but the T1D group had lower HRV at baseline. Among the measures of arterial compliance, the augmentation index declined postexercise while carotid-femoral pulse wave velocity and large artery elastic index remained unchanged. Central and brachial BP were unchanged following exercise until the final measurement, when a small increase occurred. However, arterial compliance and BP did not differ between groups. These results demonstrate that normal weight adolescents with T1D have impaired autonomic function and increased EE and fat oxidation compared to peers without diabetes who have similar levels of fitness and physical activity. However, acute cardiometabolic responses to exercise are normal in T1D with adequate glycemic control. Changes in arterial compliance and BP may take longer to emerge in relatively healthy adolescents with T1D.

Fundamental cupolets of chaotic systems.

Cupolets are a relatively new class of waveforms that represent highly accurate approximations to the unstable periodic orbits of chaotic systems, and large numbers can be efficiently generated via a control method where small kicks are applied along intersections with a control plane. Cupolets exhibit the interesting property that a given set of controls, periodically repeated, will drive the associated chaotic system onto a uniquely defined cupolet regardless of the system's initial state. We have previously demonstrated a method for efficiently steering from one cupolet to another using a graph-theoretic analysis of the connections between these orbits. In this paper, we discuss how connections between cupolets can be analyzed to show that complicated cupolets are often composed of combinations of simpler cupolets. Hence, it is possible to distinguish cupolets according to their reducibility: a cupolet is classified either as composite, if its orbit can be decomposed into the orbits of other cupolets or as fundamental, if no such decomposition is possible. In doing so, we demonstrate an algorithm that not only classifies each member of a large collection of cupolets as fundamental or composite, but that also determines a minimal set of fundamental cupolets that can exactly reconstruct the orbit of a given composite cupolet. Furthermore, this work introduces a new way to generate higher-order cupolets simply by adjoining fundamental cupolets via sequences of controlled transitions. This allows for large collections of cupolets to be collapsed onto subsets of fundamental cupolets without losing any dynamical information. We conclude by discussing potential future applications.

Sigmoidal synaptic learning produces mutual stabilization in chaotic FitzHugh-Nagumo model.

This paper investigates the interaction between two coupled neurons at the terminal end of a long chain of neurons. Specifically, we examine a bidirectional, two-cell FitzHugh-Nagumo neural model capable of exhibiting chaotic dynamics. Analysis of this model shows how mutual stabilization of the chaotic dynamics can occur through sigmoidal synaptic learning. Initially, this paper begins with a bifurcation analysis of an adapted version of a previously studied FitzHugh-Nagumo model that indicates regions of periodic and chaotic behaviors. Through allowing the synaptic properties to change dynamically via neural learning, it is shown how the system can evolve from chaotic to stable periodic behavior. The driving factor between this transition is representative of a stimulus coming down a long neural pathway. The result that two chaotic neurons can mutually stabilize via a synaptic learning implies that this may be a mechanism whereby neurons can transition from a disordered, chaotic state to a stable, ordered periodic state that persists. This approach shows that even at the simplest level of two terminal neurons, chaotic behavior can become stable, sustained periodic behavior. This is achieved without the need for a large network of neurons.

Collaborative implementation of a community-based exercise intervention with a partnering rural American Indian community.

BACKGROUND: The prevalence and socioeconomic burden of childhood obesity and diabetes has increased rapidly in the United States in the last 30 years. American Indians have the highest prevalence of type 2 diabetes among newly diagnosed youth in the country. Contributing factors include environmental, behavioral, and genetic components. Some American Indian tribal communities have explored innovative ways to combat this epidemic including collaborations with academic centers on community-based research. METHOD: From 2012 to 2017, the University of Oklahoma Health Science Center and the Choctaw Nation of Oklahoma partnered on a National Institutes of Health-funded project to determine if financial incentives would elicit an increase in physical activity in Native youth. This was a community-based behavioral intervention for overweight or obese American Indian youth ages 11-20 living in a rural community at risk for developing diabetes. RESULTS: Tribal leaders and staff identified culturally appropriate strategies to aid implementation of the trial in their community. Their identified implementation strategies helped standardize the study in order to maintain study integrity. The mutually agreed strategies included co-review of the study by tribal and University research review boards (but designation of the Choctaw Nation review board as the "Board of Record"), training of community-based staff on research ethics and literacy, standardization of the informed consent process by videotaping all study information, creation of a viable and culturally appropriate timeline for study implementation, adapting tribal wellness center operations to accommodate youth, and development of effective two-way communication through training sessions, on-site coordination, and bi-monthly conference calls. CONCLUSION: In an effort to partner collectively on a randomized clinical research trial to combat childhood diabetes, tribal leaders and staff implemented strategies that resulted in a culturally appropriate and organized community-based behavioral intervention research project.

The complete genomic sequence of Streptomyces spectabilis NRRL-2792 and identification of secondary metabolite biosynthetic gene clusters.

This is the first report of a fully annotated genomic sequence of Streptomyces spectabilis NRRL-2792, isolated and identified by The Upjohn Company in 1961. The genome was assembled into a single scaffold for annotation and analysis. The chromosome is linear, 9.5 Mb in size which is one of the largest Streptomyces genomes yet described, has a G+C content of 72%, and encodes for approximately 7943 genes. Antibiotic Secondary Metabolite Analysis Shell (antiSMASH) and Basic Local Alignment Search Tool (BLAST) bioinformatics analyses identified six complete secondary metabolite biosynthetic gene clusters for ectoine, melanin, albaflavenone, spectinomycin, 2-methylisoborneol and coelichelin. Additionally, biosynthetic clusters were identified that shared ≥ 90% gene content with complestatin, hopene, neoaureothin, or undecylprodigiosin. Thirty-one other likely secondary metabolite gene clusters were identified by antiSMASH. BLAST identified two subsets of undecylprodigiosin biosynthetic genes at polar opposites of the chromosome; their duplication was subsequently confirmed by primer walking.

Signatures of Quantum Mechanics in Chaotic Systems.

We examine the quantum-classical correspondence from a classical perspective by discussing the potential for chaotic systems to support behaviors normally associated with quantum mechanical systems. Our main analytical tool is a chaotic system's set of cupolets, which are highly-accurate stabilizations of its unstable periodic orbits. Our discussion is motivated by the bound or entangled states that we have recently detected between interacting chaotic systems, wherein pairs of cupolets are induced into a state of mutually-sustaining stabilization that can be maintained without external controls. This state is known as chaotic entanglement as it has been shown to exhibit several properties consistent with quantum entanglement. For instance, should the interaction be disturbed, the chaotic entanglement would then be broken. In this paper, we further describe chaotic entanglement and go on to address the capacity for chaotic systems to exhibit other characteristics that are conventionally associated with quantum mechanics, namely analogs to wave function collapse, various entropy definitions, the superposition of states, and the measurement problem. In doing so, we argue that these characteristics need not be regarded exclusively as quantum mechanical. We also discuss several characteristics of quantum systems that are not fully compatible with chaotic entanglement and that make quantum entanglement unique.

A single exercise session increases insulin sensitivity in normal weight and overweight/obese adolescents.

We measured the effect of an aerobic exercise session on postprandial glucose control in adolescents with habitually low-physical activity. The goal was to determine if the acute or residual response of exercise was altered in people who are overweight/obese (OW/Ob). Eleven normal weight, body mass index (NW, BMI = 48 ± 13 percentile) and 12 OW/Ob (BMI = 91 ± 5 percentile) participants completed 3 trials. In the no exercise (No Ex) trial, participants rested quietly before and after consuming a test meal. In the other 2 trials, a 45-minute aerobic exercise session was performed either 17-hour (Prior Day Ex) or 40 minutes (Same Day Ex) before the test meal. On all trials, the OW/Ob group had higher fasting glucose (~6%) and insulin (~66%), and lower insulin sensitivity (~9%) than the NW group. The Same Day Ex and Prior Day Ex trials resulted in reduced area under the curve for glucose (6% on both trials, P < .01) and insulin (15% and 13%, respectively, P < .03), and increased insulin sensitivity (8% and 6%, respectively, P < .01). The magnitudes of those effects did not differ between the NW and OW/Ob groups. Plasma fatty acids declined and carbohydrate oxidation increased after the meal, but did not differ among trials or groups. The results demonstrate that moderate intensity aerobic exercise increases insulin sensitivity in NW and OW/Ob adolescents and that the beneficial effects of exercise last up to 17 hours. The acute impact of exercise on metabolic health in adolescents is not impaired in overweight/obese participants.

Effect of obesity and type 2 diabetes, and glucose ingestion on circulating spexin concentration in adolescents.

Spexin is a novel peptide that has been reported to be down regulated in obese adults and children and in normoglycemic adults following glucose ingestion. Spexin may therefore have a role in metabolic regulation. The purpose of the current study was to determine the effect of obesity and type 2 diabetes (T2DM), and the effect of glucose ingestion on circulating spexin concentration in adolescents. Boys and girls (mean age 16 years old) classified as healthy normal weight (NW, n = 22), obese (Ob, n = 10), or obese with T2DM (n = 12) completed measurements of body composition, blood pressure, cardiorespiratory fitness, and blood concentrations of glucose, insulin, and lipids. The median fasting serum spexin concentration did not differ between groups (NW: 0.35; Ob: 0.38, T2DM: 0.34 ng/mL, respectively). In 10 NW participants who completed a standard oral glucose tolerance test, spexin concentration was unchanged at 30 and 120 minutes relative to the fasting baseline. Finally, spexin was not significantly correlated with any of the body composition, fitness, or blood biochemical measurements. These data do not support the proposed role of spexin as a metabolic regulator or biomarker of glucose control in adolescents.

Overview of Pediatric Nonalcoholic Fatty Liver Disease: A Guide for General Practitioners.

IMPORTANCE: Nonalcoholic fatty liver disease (NAFLD) is rapidly evolving into one of the most common pediatric liver diseases and currently is the most common cause for liver transplantation in young adults. Therefore, early recognition of risk factors, disease prevention, and diagnosis during childhood is paramount for effective management. OBJECTIVE: The primary objective of this review is to discuss updated recommendations for screening, diagnosis and management of NAFLD. The secondary objective is to review the extent and impact of pediatric NAFLD in Oklahoma through our center's participation in a multi-center prospective study. EVIDENCE REVIEW: We reviewed updated guidelines from the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), the approach used in our clinic and data from a multi-center collaboration on NAFLD, known as TARGET-NASH. FINDINGS: Our review highlights that obese and Hispanic children are at greatest risk for developing NAFLD. Screening with ALT should be considered between ages 9-11 years for children with BMI more than the 95th percentile. Liver biopsy is the gold standard for diagnosis of NAFLD and currently lifestyle modification is the only effective therapy for management of NAFLD. CONCLUSION AND RELEVANCE: All obese children, especially those who are Hispanics or have a family history of NAFLD should be considered for screening with serum ALT between the ages of 9 and 11 years. Children with ALT values that are elevated more than twice the upper limit of normal for more than 3 months must be referred to pediatric hepatology for timely evaluation.

The Effect of Handcycle Ergometer Exercise on Glucose Tolerance in Ambulatory and Non-Ambulatory Adolescents.

PURPOSE: Whole body or leg exercise before a meal can increase insulin sensitivity, but it is unclear whether the same can occur with upper body exercise since a smaller muscle mass is activated. We measured the impact of a single session of handcycle exercise on glucose tolerance and insulin sensitivity. METHODS: Nonambulatory (Non-Amb) adolescents with spina bifida or cerebral palsy (4F/3M), or ambulatory peers (Control, 4F/7M) completed 2 glucose tolerance tests on separate days, preceded by either rest or a 35-min bout of moderate-to-vigorous intermittent handcycle exercise. RESULTS: The Non-Amb group had higher body fat (mean ± SD: 38 ± 12%, Control: 24 ± 9, p = .041) but similar VO2peak (17.7 ± 6.1 ml/kg/min, Control: 21.1 ± 7.9). Fasting glucose and insulin were normal for all participants. Compared with the rest trial, exercise resulted in a reduction in glucose area under the curve (11%, p = .008) without a significant group x trial interaction and no difference in the magnitude of change between groups. Insulin sensitivity was increased 16% (p = .028) by exercise in the Control group but was not significantly changed in the Non-Amb group. CONCLUSION: A single bout of handcycle exercise improves glucose tolerance in adolescents with and without mobility limitations and could therefore help maintain or improve metabolic health.

Glycemic Variability Is Associated with Markers of Vascular Stress in Adolescents.

OBJECTIVES: We used continuous glucose monitoring to test the hypothesis that mean amplitude of glycemic excursions (MAGE) is associated with circulating markers of oxidative and vascular stress in adolescents with habitually low physical activity classified as healthy weight, healthy obese, or obese with type 2 diabetes mellitus (T2DM). STUDY DESIGN: A group of 13- to 21-year-olds (healthy weight = 12, healthy obese = 10, T2DM = 12) wore a continuous glucose monitor and step activity monitor for 5 days. RESULTS: Physical activity was similar among groups (6551 ± 401 steps/d), but aerobic fitness (peak rate of oxygen consumption) was lower (P < .05) in T2DM (15.6 ± 1.8 mL/kg/min) than either healthy weight (26.2 ± 2.2) or healthy obese (24.4 ± 2.5). MAGE (mg/dL) was higher (P < .01) in T2DM (82 ± 10) vs healthy obese (33 ± 3) and healthy weight (30 ± 3). Average glucose followed a similar pattern as MAGE. Oxidized low density lipoprotein was higher (P < .05) in T2DM (70.3 ± 5.0 U/L) and healthy obese (58.1 ± 3.8) than healthy weight (48.4 ± 2) and positively correlated with MAGE (r = 0.77). Other stress markers that were both elevated in T2DM and correlated with MAGE included E-selectin (r = 0.50), intercellular adhesion molecule 1 (r = 0.35), and C-reactive protein (r = 0.52); soluble receptor for advanced glycosylation end product was lower in T2DM and inversely correlated with MAGE (r = -0.38). CONCLUSIONS: MAGE is highest in obese youth with T2DM. The associations between MAGE and oxidative stress markers support the proposed contribution of glycemic variability to risk for future cardiovascular disease.

Lower resting energy expenditure and fat oxidation in Native American and Hispanic infants born to mothers with diabetes.

OBJECTIVE: To determine whether exposure to diabetes in utero affects resting energy expenditure (REE) and fuel oxidation in infants. STUDY DESIGN: At 35 ± 5 days after birth, body composition and REE were measured in full-term offspring of Native American and Hispanic women with either well-controlled diabetes (13 girls, 11 boys) or normal healthy pregnancies (18 girls, 17 boys). RESULTS: Control of dysglycemia during gestation in the women with diabetes mellitus met current clinical standards, shown by average glycated hemoglobin (5.9 ± 0.2%; 40.6 ± 2.3 mmol/mol). Infant body mass (offspring of women with diabetes: 4.78 ± 0.13, control offspring: 4.56 ± 0.08 kg) and body fatness (offspring of women with diabetes: 25.2 ± 0.6, control offspring: 24.2 ± 0.5 %) did not differ between groups. REE, adjusted for lean body mass, was 14% lower in offspring of women with diabetes (41.7 ± 2.3 kJ/h) than control offspring (48.6 ± 2.0, P = .025). Fat oxidation was 26% lower in offspring of women with diabetes (0.54 ± 0.05 g/h) than control offspring (0.76 ± 0.04, P < .01) but carbohydrate oxidation did not differ. Thus, fat oxidation accounted for a lower fraction of REE in the offspring of women with diabetes (49 ± 4%) than control offspring (60 ± 3%, P = .022). Mothers with diabetes were older and had higher prepregnancy body mass index than control mothers. CONCLUSIONS: Well-controlled maternal diabetes did not significantly affect body mass or composition of offspring at 1-month old. However, infants with mothers with diabetes had reduced REE and fat oxidation, which could contribute to adiposity and future disease risk. Further studies are needed to assess the impact differences in age and higher prepregnancy body mass index.

Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus.

BACKGROUND: Offspring of women with diabetes mellitus (DM) during pregnancy have a risk of developing metabolic disease in adulthood greater than that conferred by genetics alone. The mechanisms responsible are unknown, but likely involve fetal exposure to the in utero milieu, including glucose and circulating adipokines. The purpose of this study was to assess the impact of maternal DM on fetal adipokines and anthropometry in infants of Hispanic and Native American women. METHODS: We conducted a prospective study of offspring of mothers with normoglycemia (Con-O; n = 79) or type 2 or gestational DM (DM-O; n = 45) pregnancies. Infant anthropometrics were measured at birth and 1-month of age. Cord leptin, high-molecular-weight adiponectin (HMWA), pigment epithelium-derived factor (PEDF) and C-peptide were measured by ELISA. Differences between groups were assessed using the Generalized Linear Model framework. Correlations were calculated as standardized regression coefficients and adjusted for significant covariates. RESULTS: DM-O were heavier at birth than Con-O (3.7 ± 0.6 vs. 3.4 ± 0.4 kg, p = 0.024), but sum of skinfolds (SSF) were not different. At 1-month, there was no difference in weight, SSF or % body fat or postnatal growth between groups. Leptin was higher in DM-O (20.1 ± 14.9 vs. 9.5 ± 9.9 ng/ml in Con-O, p < 0.0001). Leptin was positively associated with birth weight (p = 0.0007) and SSF (p = 0.002) in Con-O and with maternal hemoglobin A1c in both groups (Con-O, p = 0.023; DM-O, p = 0.006). PEDF was positively associated with birth weight in all infants (p = 0.004). Leptin was positively associated with PEDF in both groups, with a stronger correlation in DM-O (p = 0.009). At 1-month, HMWA was positively associated with body weight (p = 0.004), SSF (p = 0.025) and % body fat (p = 0.004) across the cohort. CONCLUSIONS: Maternal DM results in fetal hyperleptinemia independent of adiposity. HMWA appears to influence postnatal growth. Thus, in utero exposure to DM imparts hormonal differences on infants even without aberrant growth.

Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration.

Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 µg tri-iodothyronine (T3) in 7- and 27-mo-old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones. The increased food intake in the young rats corresponded with a T3-mediated increase in the appetite-regulating proteins agouti-related peptide, neuropeptide Y, and uncoupling protein 2 in the hypothalamus, but no increase occurred in the old rats. Evidence of mitochondrial biogenesis in response to T3 was similar in the soleus muscle and heart of the young and old animals, but less consistent in old plantaris muscle and liver. Despite the comparable increase in EE, T3's effect on mitochondrial function was modulated by age in a tissue-specific manner. We conclude that older rats lack compensatory mechanisms to increase caloric intake in response to a T3-induced increase in EE, demonstrating a detrimental effect of age on energy homeostasis.

Elevated plasma pigment epithelium-derived factor in children with type 2 diabetes mellitus is attributable to obesity.

BACKGROUND: Pigment epithelium-derived factor (PEDF) is a member of the serpin family secreted by adipocytes. Plasma PEDF is increased in obese children and adults. Adults with type 2 diabetes mellitus (T2DM) have higher circulating PEDF but there are no reports in children with T2DM. OBJECTIVE: To compare PEDF concentration in children with T2DM to normal weight and obese children without T2DM and determine associations with anthropometric or serum factors. METHODS: Participants were 34 obese children with T2DM diagnosed by American Diabetes Association (ADA) criteria, 61 normal weight [body mass index (BMI) 25-75 percentile] and 63 obese (BMI ≥ 95 percentile) children of age 8-18 yr. Plasma PEDF was measured in fasting plasma samples. Anthropometric, serum, and body composition (dual-energy x-ray absorptiometry, DXA) data were obtained for each subject to identify potential predictor variables. RESULTS: PEDF was 55% higher (p = 0.001) in the T2DM group compared with normal weight children, but did not differ from obese children. In the T2DM group, fat mass and lean mass both individually predicted PEDF (r² = 0.22 and 0.17, p = 0.02 and p < 0.01, respectively). PEDF was positively correlated with homeostatic model assessment - insulin resistance (HOMA-IR) when all groups were combined (r² = 0.15, p<0.001). CONCLUSIONS: Plasma PEDF was similar in the T2DM and obese groups, therefore, obesity, rather than diabetes, may account for the higher PEDF in children with T2DM compared with normal weight children. PEDF was positively associated with both lean mass and fat mass both of which may contribute to the circulating level of the protein, and potentially to PEDF's association with insulin resistance in obese children with and without diabetes.

Arterial compliance in obese children: implications for cardiovascular health.

Recent work showed that arterial compliance may be elevated unexpectedly in obese children, attributable to accelerated growth and maturation. We hypothesize that children with obesity or Type 2 diabetes may reach peak arterial maturation earlier in life and then experience an earlier, and potentially more rapid, decline in arterial compliance, leading toward earlier cardiovascular disease development.

Controlled transitions between cupolets of chaotic systems.

We present an efficient control scheme that stabilizes the unstable periodic orbits of a chaotic system. The resulting orbits are known as cupolets and collectively provide an important skeleton for the dynamical system. Cupolets exhibit the interesting property that a given sequence of controls will uniquely identify a cupolet, regardless of the system's initial state. This makes it possible to transition between cupolets, and thus unstable periodic orbits, simply by switching control sequences. We demonstrate that although these transitions require minimal controls, they may also involve significant chaotic transients unless carefully controlled. As a result, we present an effective technique that relies on Dijkstra's shortest path algorithm from algebraic graph theory to minimize the transients and also to induce certainty into the control of nonlinear systems, effectively providing an efficient algorithm for the steering and targeting of chaotic systems.