A new Sigma-Pi-Sigma neural network based on L1 L_1 and L2 L_2 regularization and applications

As one type of the important higher-order neural networks developed in the last decade, the Sigma-Pi-Sigma neural network has more powerful nonlinear mapping capabilities compared with other popular neural networks. This paper is concerned with a new Sigma-Pi-Sigma neural network based on a $L_1$ and $L_2$ regularization batch gradient method, and the numerical experiments for classification and regression problems prove that the proposed algorithm is effective and has better properties comparing with other classical penalization methods. The proposed model combines the sparse solution tendency of $L_1$ norm and the high benefits in efficiency of the $L_2$ norm, which can regulate the complexity of a network and prevent overfitting. Also, the numerical oscillation, induced by the non-differentiability of $L_1$ plus $L_2$ regularization at the origin, can be eliminated by a smoothing technique to approximate the objective function

Modeling Three-dimensional Invasive Solid Tumor Growth in Heterogeneous Microenvironment under Chemotherapy

A systematic understanding of the evolution and growth dynamics of invasive solid tumors in response to different chemotherapy strategies is crucial for the development of individually optimized oncotherapy. Here, we develop a hybrid three-dimensional (3D) computational model that integrates pharmacokinetic model, continuum diffusion-reaction model and discrete cell automaton model to investigate 3D invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. Specifically, we consider the effects of heterogeneous environment on drug diffusion, tumor growth, invasion and the drug-tumor interaction on individual cell level. We employ the hybrid model to investigate the evolution and growth dynamics of avascular invasive solid tumors under different chemotherapy strategies. Our simulations reproduce the well-established observation that constant dosing is generally more effective in suppressing primary tumor growth than periodic dosing, due to the resulting continuous high drug concentration. In highly heterogeneous microenvironment, the malignancy of the tumor is significantly enhanced, leading to inefficiency of chemotherapies. The effects of geometrically-confined microenvironment and non-uniform drug dosing are also investigated. Our computational model, when supplemented with sufficient clinical data, could eventually lead to the development of efficient in silico tools for prognosis and treatment strategy optimization.Comment: 41 pages, 8 figure

Resolvin D1 and Aspirin-Triggered Resolvin D1 Regulate Histamine-stimulated Conjunctival Goblet Cell Secretion

Resolution of inflammation is an active process mediated by pro-resolution lipid mediators. Since resolvin (Rv) D1 is produced in the cornea, pro-resolution mediators could be effective in regulating inflammatory responses to histamine in allergic conjunctivitis. Two key mediators of resolution are the D-series resolvins RvD1 or aspirin-triggered RvD1 (AT-RvD1). We used cultured conjunctival goblet cells to determine whether histamine actions can be terminated during allergic responses. We found cross-talk between two types of G protein-coupled receptors, as RvD1 interacts with its receptor GPR32 to block histamine-stimulated H1 receptor increases in intracellular [Ca2+] ([Ca2+]i) preventing H1 receptor-mediated responses. In human and rat conjunctival goblet cells RvD1 and AT-RvD1 each block histamine-stimulated secretion by preventing its increase in [Ca2+]i and activation of extracellular regulated protein kinase (ERK)1/2. We suggest that D-series resolvins regulate histamine responses in the eye and offer new treatment approaches for allergic conjunctivitis or other histamine-dependent pathologies

Expression of NR2B in Cerebellar Granule Cells Specifically Facilitates Effect of Motor Training on Motor Learning

It is believed that gene/environment interaction (GEI) plays a pivotal role in the development of motor skills, which are acquired via practicing or motor training. However, the underlying molecular/neuronal mechanisms are still unclear. Here, we reported that the expression of NR2B, a subunit of NMDA receptors, in cerebellar granule cells specifically enhanced the effect of voluntary motor training on motor learning in the mouse. Moreover, this effect was characterized as motor learning-specific and developmental stage-dependent, because neither emotional/spatial memory was affected nor was the enhanced motor learning observed when the motor training was conducted starting at the age of 3 months old in these transgenic mice. These results indicate that changes in the expression of gene(s) that are involved in regulating synaptic plasticity in cerebellar granule cells may constitute a molecular basis for the cerebellum to be involved in the GEI by facilitating motor skill learning

Research on the development law of karst caves on water conducting fractures under the influence of mining in Southwest Karst Mining Areas

Southwest Guizhou mining area is a typical karst development mining area in China. Under the influence of mining, the height of karst roof water conducting cracks is abnormally developed. During the rainy season, atmospheric precipitation is extremely easy to enter the underground working face through ultra-high water conducting channels, causing water inrush disasters at the working face, seriously affecting the normal production of the mine. Therefore, based on the analysis of the occurrence characteristics of karst caves in Xintian Coal Mine, the development rules of karst roof water conducting fracture zones during mining were studied by means of on-site measurement, indoor simulation, and theoretical analysis. The development mechanism of ultra-high water conducting fractures was revealed. The results show that: ①The roof karst caves in the study area have obvious zonation phenomenon from top to bottom in the layers such as the surface, the Yulongshan section, and the Changxing Formation. The surface water holes develop along the gullies, and the karst caves in the upper and middle parts of the strong aquifer in the Yulongshan section develop, presenting different forms of beads. The Changxing Formation only locally hosts karst caves with smaller diameters; ② Karst caves in karst aquifers have an important impact on water conducting fractures. Without karst caves, the development height of water conducting fractures is 43.1 m, and the fracture mining ratio is 14.4. Under karst caves, the development of water conducting fractures is abnormal, with a height of 173.1 m, and a fracture mining ratio of 57.7, which communicates with the strong limestone aquifer in the Yulong Mountain section; ③ Karst roof water conducting fissures consist of two parts: mining upward fissures and karst cave instability downward fissures. Under the influence of mining, karst caves become unstable under the combined action of concentrated stress and mining additional stress, and are prone to form downward fissures, which communicate with mining upward fissures, ultimately forming a special ultra-high water conducting fissure in southwestern Guizhou mining area

Insights on Flexible Zinc‐Ion Batteries from Lab Research to Commercialization

Owing to the development of aqueous rechargeable zinc-ion batteries (ZIBs), flexible ZIBs are deemed as potential candidates to power wearable electronics. ZIBs with solid-state polymer electrolytes can not only maintain additional load-bearing properties, but exhibit enhanced electrochemical properties by preventing dendrite formation and inhibiting cathode dissolution. Substantial efforts have been applied to polymer electrolytes by developing solid polymer electrolytes, hydrogel polymer electrolytes, and hybrid polymer electrolytes; however, the research of polymer electrolytes for ZIBs is still immature. Herein, the recent progress in polymer electrolytes is summarized by category for flexible ZIBs, especially hydrogel electrolytes, including their synthesis and characterization. Aiming to provide an insight from lab research to commercialization, the relevant challenges, device configurations, and life cycle analysis are consolidated. As flexible batteries, the majority of polymer electrolytes exploited so far only emphasizes the electrochemical performance but the mechanical behavior and interactions with the electrode materials have hardly been considered. Hence, strategies of combining softness and strength and the integration with electrodes are discussed for flexible ZIBs. A ranking index, combining both electrochemical and mechanical properties, is introduced. Future research directions are also covered to guide research toward the commercialization of flexible ZIBs

Morphological quantification of proliferation-to-invasion transition in tumor spheroids

Abstract(#br)Background(#br)Metastasis determines the lethality of cancer. In most clinical cases, patients are able to live with tumor proliferation before metastasis. Thus, the transition from tumor proliferation to metastasis/invasion is essential. However, the mechanism is still unclear and especially, the proliferation-to-metastasis/invasion transition point has not been well defined. Therefore, quantitative characterization of this transition is urgently needed.(#br)Methods(#br)We have successfully developed a home-built living-cell incubation system combined with an inverted optical microscope, and a systematic, quantitative approach to describing the major characteristic morphological parameters for the identification of the critical transition points for tumor-cell spheroids in a collagen fiber scaffold.(#br)Results(#br)The system focuses on in vitro tumor modeling, e.g. the development of tumor-cell spheroids in a collagen fiber scaffold and the monitoring of cell transition from proliferation to invasion. By applying this approach to multiple tumor spheroid models, such as U87 (glioma tumor), H1299 (lung cancer), and MDA-MB-231 (breast cancer) cells, we have obtained quantitative morphological references to evaluate the proliferation-to-invasion transition time, as well as differentiating the invasion potential of tumor cells upon environmental changes, i.e. drug application.(#br)Conclusions(#br)Our quantitative approach provides a feasible clarification for the proliferation-to-invasion transition of in vitro tumor models (spheroids). Moreover, the transition time is a useful reference for the invasive potential of tumor cells.(#br)General significance(#br)This quantitative approach is potentially applicable to primary tumor cells, and thus has potential applications in the fields of cancer metastasis investigations and clinical diagnostics