IonMonger: a free and fast planar perovskite solar cell simulator with coupled ion vacancy and charge carrier dynamics

Details of an open-source planar perovskite solar cell simulator, that includes ion vacancy migration within the perovskite layer coupled to charge carrier transport throughout the perovskite and adjoining transport layers in one dimension, are presented. The model equations are discretised in space using a finite element scheme and temporal integration of the resulting system of differential-algebraic equations is carried out in MATLAB. The user is free to modify device parameters, as well as the incident illumination and applied voltage. Time-varying voltage and/or illumination protocols can be specified, e.g. to simulate current-voltage sweeps, or to track the open-circuit conditions as the illumination is varied. Typical simulations, e.g. current-voltage sweeps, only require computation times of seconds to minutes on a modern personal computer. An example set of hysteretic current-voltage curves is presented

Characterizing Dynamic Interactions between Ultradian Glucocorticoid Rhythmicity and Acute Stress Using the Phase Response Curve

The hypothalamic-pituitary-adrenal (HPA) axis is a dynamic oscillatory hormone signalling system that regulates the pulsatile secretion of glucocorticoids from the adrenal glands. In addition to regulation of basal levels of glucocorticoids, the HPA axis provides a rapid hormonal response to stress that is vitally important for homeostasis. Recently it has become clear that glucocorticoid pulses encode an important biological signal that regulates receptor signalling both in the central nervous system and in peripheral tissues. It is therefore important to understand how stressful stimuli disrupt the pulsatile dynamics of this system. Using a computational model that incorporates the crucial feed-forward and feedback components of the axis, we provide novel insight into experimental observations that the size of the stress-induced hormonal response is critically dependent on the timing of the stress. Further, we employ the theory of Phase Response Curves to show that an acute stressor acts as a phase-resetting mechanism for the ultradian rhythm of glucocorticoid secretion. Using our model, we demonstrate that the magnitude of an acute stress is a critical factor in determining whether the system resets via a Type 1 or Type 0 mechanism. By fitting our model to our in vivo stress-response data, we show that the glucocorticoid response to an acute noise stress in rats is governed by a Type 0 phase-resetting curve. Our results provide additional evidence for the concept of a deterministic sub-hypothalamic oscillator regulating the ultradian glucocorticoid rhythm, which constitutes a highly responsive peripheral hormone system that interacts dynamically with hypothalamic inputs to regulate the overall hormonal response to stress

Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses.

Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full-thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord-blood derived equine MSCs were applied to each wound 1 day after wound creation, in one of four forms: (a) normoxic- or (b) hypoxic-preconditioned cells injected into wound margins, or (c) normoxic- or (d) hypoxic-preconditioned cells embedded in an autologous fibrin gel and applied topically to the wound bed. Controls were one blank (saline) injected wound and one blank fibrin gel-treated wound per horse. Data were collected weekly for 6 weeks and included wound surface area, thermography, gene expression, and histologic scoring. Results indicated that MSC treatment by either delivery method was safe and improved histologic outcomes and wound area. Hypoxic-preconditioning did not offer an advantage. MSC treatment by injection resulted in statistically significant increases in transforming growth factor beta and cyclooxygenase-2 expression at week 1. Histologically, significantly more MSC-treated wounds were categorized as pro-healing than pro-inflammatory. Wound area was significantly affected by treatment: MSC-injected wounds were consistently smaller than gel-treated or control wounds. In conclusion, MSC therapy shows promise for distal extremity wounds in horses, particularly when applied by direct injection into the wound margin. Stem Cells Translational Medicine 2018;7:98-108

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Origin of ultradian pulsatility in the hypothalamic–pituitary–adrenal axis

The hypothalamic–pituitary–adrenal (HPA) axis is a neuroendocrine system that regulates the circulating levels of vital glucocorticoid hormones. The activity of the HPA axis is characterized not only by a classic circadian rhythm, but also by an ultradian pattern of discrete pulsatile release of glucocorticoids. A number of psychiatric and metabolic diseases are associated with changes in glucocorticoid pulsatility, and it is now clear that glucocorticoid responsive genes respond to these rapid fluctuations in a biologically meaningful way. Theoretical modelling has enabled us to identify and explore potential mechanisms underlying the ultradian activity in this axis, which to date have not been identified successfully. We demonstrate that the combination of delay with feed-forward and feedback loops in the pituitary–adrenal system is sufficient to give rise to ultradian pulsatility in the absence of an ultradian source from a supra-pituitary site. Moreover, our model enables us to predict the different patterns of glucocorticoid release mediated by changes in hypophysial-portal corticotrophin-releasing hormone levels, with results that parallel our experimental in vivo data

Modelling the dynamic interaction of systemic inflammation and the hypothalamic-pituitary-adrenal (HPA) axis during and after cardiac surgery

Major surgery and critical illness produce a potentially life-threatening systemic inflammatory response. The hypothalamic–pituitary–adrenal (HPA) axis is one of the key physiological systems that counterbalances this systemic inflammation through changes in adrenocorticotrophic hormone (ACTH) and cortisol. These hormones normally exhibit highly correlated ultradian pulsatility with an amplitude modulated by circadian processes. However, these dynamics are disrupted by major surgery and critical illness. In this work, we characterize the inflammatory, ACTH and cortisol responses of patients undergoing cardiac surgery and show that the HPA axis response can be classified into one of three phenotypes: single-pulse, two-pulse and multiple-pulse dynamics. We develop a mathematical model of cortisol secretion and metabolism that predicts the physiological mechanisms responsible for these different phenotypes. We show that the effects of inflammatory mediators are important only in the single-pulse pattern in which normal pulsatility is lost—suggesting that this phenotype could be indicative of the greatest inflammatory response. Investigating whether and how these phenotypes are correlated with clinical outcomes will be critical to patient prognosis and designing interventions to improve recovery