Influence of initial distributions on robust cooperation in evolutionary Prisoner's Dilemma

We study the evolutionary Prisoner's Dilemma game on scale-free networks for different initial distributions. We consider three types of initial distributions for cooperators and defectors: initially random distribution with different frequencies of defectors; intentional organization with defectors initially occupying the most connected nodes with different fractions of defectors; intentional assignment for cooperators occupying the most connected nodes with different proportions of defectors at the beginning. It is shown that initial configurations for cooperators and defectors can influence the stationary level of cooperation and the evolution speed of cooperation. Organizations with the vertices with highest connectivity representing individuals cooperators could exhibit the most robust cooperation and drive evolutionary process to converge fastest to the high steady cooperation in the three situations of initial distributions. Otherwise, we determine the critical initial frequencies of defectors above which the extinction of cooperators occurs for the respective initial distributions, and find that the presence of network loops and clusters for cooperators can favor the emergence of cooperation.Comment: Submitted to EP

Sequential Wnt Agonist then Antagonist Treatment Accelerates Tissue Repair and Minimizes Fibrosis

Tissue fibrosis compromises organ function and occurs as a potential long-term outcome in response to acute tissue injuries. Currently, lack of mechanistic understanding prevents effective prevention and treatment of the progression from acute injury to fibrosis. Here, we combined quantitative experimental studies with a mouse kidney injury model and a computational approach to determine how the physiological consequences are determined by the severity of ischemia injury, and to identify how to manipulate Wnt signaling to accelerate repair of ischemic tissue damage while minimizing fibrosis. The study reveals that Wnt-mediated memory of prior injury contributes to fibrosis progression, and ischemic preconditioning reduces the risk of death but increases the risk of fibrosis. Furthermore, we validated the prediction that sequential combination therapy of initial treatment with a Wnt agonist followed by treatment with a Wnt antagonist can reduce both the risk of death and fibrosis in response to acute injuries

Positive Solutions for a Class of Third-Order Three-Point Boundary Value Problem

We investigate the problem of existence of positive solutions for the nonlinear third-order three-point boundary value problem u‴(t)+λa(t)f(u(t))=0, 0<t<1, u(0)=u′(0)=0, u″(1)=∝u″(η), where λ is a positive parameter, ∝∈(0,1), η∈(0,1), f:(0,∞)→(0,∞), a:(0,1)→(0,∞) are continuous. Using a specially constructed cone, the fixed point index theorems and Leray-Schauder degree, this work shows the existence and multiplicities of positive solutions for the nonlinear third-order boundary value problem. Some examples are given to demonstrate the main results

Nanoelectronics-Biology Frontier: From Nanoscopic Probes for Action Potential Recording in Live Cells to Three-Dimensional Cyborg Tissues

Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signals with high signal-to-noise ratio and temporal resolution from cultured neurons, cultured cardiomyocytes, acute brain slices and whole animal hearts. Measurements made with modulation-doped nanoscale active channel SiNW FETs demonstrate that signals recorded from cardiomyocytes are highly localized and have improved time resolution compared to larger planar detectors. In addition, several novel three-dimensional (3D) transistor probes, which were realized using advanced nanowire synthesis methods, have been implemented for intracellular recording. These novel probes include (i) flexible 3D kinked nanowire FETs, (ii) branched intracellular nanotube SiNW FETs, and (iii) active silicon nanotube FETs. Following phospholipid modification of the probes to mimic the cell membrane, the kinked nanowire, branched intracellular nanotube and active silicon nanotube FET probes recorded full-amplitude intracellular action potentials from spontaneously firing cardiomyocytes. Moreover, these probes demonstrated the capability of reversible, stable, and long-term intracellular recording, thus indicating the minimal invasiveness of the new nanoscale structures and suggesting biomimetic internalization via the phospholipid modification. Simultaneous, multi-site intracellular recording from both single cells and cell networks were also readily achieved by interfacing independently addressable nanoprobe devices with cells. Finally, electronic and biological systems have been seamlessly merged in 3D for the first time using macroporous nanoelectronic scaffolds that are analogous to synthetic tissue scaffold and the extracellular matrix in tissue. Free-standing 3D nanoelectronic scaffolds were cultured with neurons, cardiomyocytes and smooth muscle cells to yield electronically-innervated synthetic or ‘cyborg’ tissues. Measurements demonstrate that innervated tissues exhibit similar cell viability as with conventional tissue scaffolds, and importantly, demonstrate that the real-time response to drugs and pH changes can be mapped in 3D through the tissues. These results open up a new field of research, wherein nanoelectronics are merged with biological systems in 3D thereby providing broad opportunities, ranging from a nanoelectronic/tissue platform for real-time pharmacological screening in 3D to implantable ‘cyborg’ tissues enabling closed-loop monitoring and treatment of diseases. Furthermore, the capability of high density scale-up of the above extra- and intracellular nanoscopic probes for action potential recording provide important tools for large-scale high spatio-temporal resolution electrical neural activity mapping in both 2D and 3D, which promises to have a profound impact on many research areas, including the mapping of activity within the brain.Chemistry and Chemical BiologyEngineering and Applied Science

Duszność spowodowana gruźliczakami powstającymi w rdzeniu przedłużonym w czasie leczenia gruźliczego zapalenia opon mózgowo-rdzeniowych

Formation of tuberculoma is a rare response of neurotuberculosis in patients regularly and adequately treated with anti-tuberculous drugs. We report a 13-year-old girl with two tuberculomas which formed in the dorsal part of the medulla oblongata during chemotherapy for tuberculous meningitis. The tuberculomas were both removed via a suboccipital midline approach and were demonstrated by pathological findings but the girl died of cardiac arrest that was thought to be caused by postoperative medulla oblongata oedema. In combination with a literature review, we discuss the clinical features and treatment options of brainstem tuberculomas.Tworzenie się gruźliczaka jest rzadką reakcją w przebiegu właściwie leczonej gruźlicy układu nerwowego. W pracy autorzy opisują przypadek 13-letniej dziewczynki z dwoma gruźliczakami, które utworzyły się w grzbietowej części rdzenia przedłużonego w czasie farmakologicznego leczenia gruźliczego zapalenia opon mózgowo-rdzeniowych. Oba gruźliczaki usunięto z dostępu podpotylicznego w linii środkowej i potwierdzono ich rozpoznanie w badaniu histopatologicznym, ale pacjentka zmarła w wyniku zatrzymania krążenia, przypuszczalnie wskutek pooperacyjnego obrzęku rdzenia przedłużonego. Na podstawie przedstawionego przypadku i przeglądu piśmiennictwa omówiono objawy kliniczne i możliwości leczenia gruźliczaków pnia mózgu

Soluble epoxide hydrolase inhibitor promotes the healing of oral ulcers

Objective: Oral ulcers are a lesion in the oral mucosa that impacts chewing or drinking. Epoxyeicosatrienoic Acids (EETs) have enhanced angiogenic, regenerative, anti-inflammatory, and analgesic effects. The present study aims to evaluate the effects of 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea (TPPU), a soluble epoxide hydrolase inhibitor for increasing EETs level, on the healing of oral ulcers. Methods: The chemically-induced oral ulcers were established in Sprague Dawley rats. The ulcer area was treated with TPPU to evaluate the healing time and pain threshold of ulcers. The expression of angiogenesis and cell proliferation-related protein in the ulcer area was detected using immunohistochemical staining. The effects of TPPU on migration and angiogenesis capability were measured with scratch assay and tube formation. Results: Compared with the control group, TPPU promoted wound healing of oral ulcers with a shorter healing time, and raised pain thresholds. Immunohistochemical staining showed that TPPU increased the expression of angiogenesis and cell proliferation-related protein with reduced inflammatory cell infiltration in the ulcer area. TPPU enhanced cell migration and tube-forming potential&nbsp;in vitro. Conclusions: The present results support the potential of TPPU with multiple biological effects for the treatment of oral ulcers by targeting soluble epoxide hydrolase

Sub-10-nm Intracellular Bioelectronic Probes from Nanowire-Nanotube Heterostructures

The miniaturization of bioelectronic intracellular probes with a wide dynamic frequency range can open up opportunities to study biological structures inaccessible by existing methods in a minimally invasive manner. Here, we report the design, fabrication, and demonstration of intracellular bioelectronic devices with probe sizes less than 10 nm. The devices are based on a nanowire–nanotube heterostructure in which a nanowire field-effect transistor detector is synthetically integrated with a nanotube cellular probe. Sub-10-nm nanotube probes were realized by a two-step selective etching approach that reduces the diameter of the nanotube free-end while maintaining a larger diameter at the nanowire detector necessary for mechanical strength and electrical sensitivity. Quasi-static water-gate measurements demonstrated selective device response to solution inside the nanotube, and pulsed measurements together with numerical simulations confirmed the capability to record fast electrophysiological signals. Systematic studies of the probe bandwidth in different ionic concentration solutions revealed the underlying mechanism governing the time response. In addition, the bandwidth effect of phospholipid coatings, which are important for intracellular recording, was investigated and modeled. The robustness of these sub-10-nm bioelectronics probes for intracellular interrogation was verified by optical imaging and recording the transmembrane resting potential of HL-1 cells. These ultrasmall bioelectronic probes enable direct detection of cellular electrical activity with highest spatial resolution achieved to date, and with further integration into larger chip arrays could provide a unique platform for ultra-high-resolution mapping of activity in neural networks and other systems.Chemistry and Chemical BiologyEngineering and Applied Science