An Extensible Mathematical Model of Glucose Metabolism

The American Diabetes Association reports that diabetes is the fifth leading cause of death by disease in the United States. An estimated 23.6 million individuals, or seven percent of the population, have diabetes. Nearly one-third are unaware that they have the disease. The total of the direct and indirect medical costs associated with diabetes in 2007 was projected to be $174 billion, or approximately one out of every ten health care dollars. One must understand the glucose regulatory system of the healthy body to understand diabetes. Blood glucose concentration returns to a constant level after eating and is maintained during exercise. With thousands of chemical reactions involved in the process, a complete mathematical model is not yet realistic. Proposed here is the evolution of a model beginning with a three-variable model of glucose, insulin, and glucagon and ending with its extension to the four-variable model incorporating the additional interdependent mechanics of hepatic glycogen. The three-variable model mimics the return of blood glucose levels to a constant, or basal, state; however, this model is consistent only with short-term dynamics since it excludes consideration of finite energy stores. Thus, the extension includes the effects of a finite store of hepatic glycogen. The solution of the four-variable model demonstrates the short-term return of glucose concentration to near basal levels despite the constant energy usage which draws upon the glycogen stores. Long-term glucose homeostasis is explained by investigating the storage of a glucose load in the postprandial period and dispersion of stored glucose during the extended postprandial period. Increased hepatic glucose production in people with diabetes is thought to be the driving mechanism for increased basal glucose levels. Analysis of this model indicates the genesis of this phenomenon. Elevated prandial glucose and insulin levels associated with insulin resistance increase the glycogen-storage levels above normal which then increase hepatic glucose production in the postprandial period. Increased energy input exasperates this problem, but only in insulin resistant individuals. This simple model suggests that Type II diabetes results from insulin resistance more than from overeating

An Extensible Mathematical Model of Glucose Metabolism. Part I: The Basic Glucose-Insulin-Glucagon Model, Basal Conditions and Basic Dynamics

A basic model highlighting the counter-regulatory roles of insulin and glucagon is proposed to start a series of models designed to explore continuous rein control and major aspects of glucose metabolism. The three-by-three dynamical system uses black boxes to model unit processes such as the dependencies of insulin secretion rate and the glucagon secretion rate on blood glucose concentration. The dependency of basal conditions on insulin resistance and any defects in insulin or glucagon secretion are shown. Since over-production of hepatic glucose exists early in the history of diabetes, it is important that mathematical models should account for this effect by inclusion of the dynamical equation governing glucagon concentration as this illustrative model does. All solutions are consistent with gross features of the metabolic process. The model is examined for explicit and implicit assumptions affecting its validity which determines that the first extension to the model should account for glucose storage and the release of stored glucose

The Spectral Ocean Color Imager (SPOC) – An Adjustable Multispectral Imager

SPOC (SPectral Ocean Color) is a 3U small satellite mission that will use an adjustable multispectral imager to map sensitive coastal regions and off coast water quality of Georgia and beyond. SPOC is being developed by the University of Georgia’s (UGA) Small Satellite Research Laboratory (SSRL) through NASA’s Undergraduate Student Instrument Project (USIP). UGA is working with Cloudland Instruments to develop a small scale (\u3c 1000 \u3ecm3) multispectral imager, ranging from 400-850nm, for Earth science applications which will fly as part of the NASA CubeSat Launch Initiative. The project is UGA’s first satellite mission and is built by a team of undergraduates from a wide range of backgrounds and supervised by a multidisciplinary team of graduate students and faculty. Development, assembly, testing, and validation of the multispectral imager, as well integrating it into the satellite are all being done in house. At an orbit of 400 km the resulting images will be 90 km x 100 km in size, with a default spatial resolution and spectral resolution of 130 m and 4 nm, respectively

A unified framework for the orbital structure of bars and triaxial ellipsoids

We examine a large random sample of orbits in two self-consistent simulations of N-body bars. Orbits in these bars are classified both visually and with a new automated orbit classification method based on frequency analysis. The well-known prograde x1 orbit family originates from the same parent orbit as the box orbits in stationary and rotating triaxial ellipsoids. However, only a small fraction of bar orbits (~4%) have predominately prograde motion like their periodic parent orbit. Most bar orbits arising from the x1 orbit have little net angular momentum in the bar frame, making them equivalent to box orbits in rotating triaxial potentials. In these simulations a small fraction of bar orbits (~7%) are long-axis tubes that behave exactly like those in triaxial ellipsoids: they are tipped about the intermediate axis owing to the Coriolis force, with the sense of tipping determined by the sign of their angular momentum about the long axis. No orbits parented by prograde periodic x2 orbits are found in the pure bar model, but a tiny population (~2%) of short-axis tube orbits parented by retrograde x4 orbits are found. When a central point mass representing a supermassive black hole (SMBH) is grown adiabatically at the center of the bar, those orbits that lie in the immediate vicinity of the SMBH are transformed into precessing Keplerian orbits that belong to the same major families (short-axis tubes, long-axis tubes and boxes) occupying the bar at larger radii. During the growth of an SMBH, the inflow of mass and outward transport of angular momentum transform some x1 and long-axis tube orbits into prograde short-axis tubes. This study has important implications for future attempts to constrain the masses of SMBHs in barred galaxies using orbit-based methods like the Schwarzschild orbit superposition scheme and for understanding the observed features in barred galaxies

MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor-1.

The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)-1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC-HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC-HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies

Combining genomic and epidemiological data to compare the transmissibility of SARS-CoV-2 variants Alpha and Iota.

SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surveillance data to estimate the effective reproduction number (Rt) of the variants. We use Connecticut, United States, in which Alpha and Iota co-circulated in 2021. We find that the Rt of these variants were up to 50% larger than that of other variants. We then use phylogeography to show that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of Alpha were larger than those resulting from Iota introductions. By monitoring the dynamics of individual variants throughout our study period, we demonstrate the importance of routine surveillance in the response to COVID-19

Increased Incidence of Vestibular Disorders in Patients With SARS-CoV-2

OBJECTIVE: Determine the incidence of vestibular disorders in patients with SARS-CoV-2 compared to the control population. STUDY DESIGN: Retrospective. SETTING: Clinical data in the National COVID Cohort Collaborative database (N3C). METHODS: Deidentified patient data from the National COVID Cohort Collaborative database (N3C) were queried based on variant peak prevalence (untyped, alpha, delta, omicron 21K, and omicron 23A) from covariants.org to retrospectively analyze the incidence of vestibular disorders in patients with SARS-CoV-2 compared to control population, consisting of patients without documented evidence of COVID infection during the same period. RESULTS: Patients testing positive for COVID-19 were significantly more likely to have a vestibular disorder compared to the control population. Compared to control patients, the odds ratio of vestibular disorders was significantly elevated in patients with untyped (odds ratio [OR], 2.39; confidence intervals [CI], 2.29-2.50; CONCLUSIONS: The incidence of vestibular disorders differed between COVID-19 variants and was significantly elevated in COVID-19-positive patients compared to the control population. These findings have implications for patient counseling and further research is needed to discern the long-term effects of these findings