APPLICATION OF THE RESIDUE THEOREM TO BILATERAL HYPERGEOMETRIC SERIES

The application of the residue theorem to bilateral hypergeometric series identities is systematically reviewed by exemplifying three classes of summation theorems due to Dougall (1907), Jackson (1949, 1952) and Slater-Lakin (1953).The application of the residue theorem to bilateral hypergeometric series identities is systematically reviewed by exemplifying three classes of summation theorems due to Dougall (1907), Jackson (1949, 1952) and Slater-Lakin (1953)

Intrinsic Cerebro-Cerebellar Functional Connectivity Reveals the Function of Cerebellum VI in Reading-Related Skills

Funding This work was supported by grants from the National Natural Science Foundation of China (NSFC: 31971036, 31971039, and 31571158).Peer reviewedPublisher PD

Interleukin-22 Inhibits Bleomycin-Induced Pulmonary Fibrosis

Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL-) 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM-) induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced γδT cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT) and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker (α-smooth muscle actin (α-SMA)) and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis

Characterization of Defects in Ion Transport and Tissue Development in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Knockout Rats

Animal models for cystic fibrosis (CF) have contributed significantly to our understanding of disease pathogenesis. Here we describe development and characterization of the first cystic fibrosis rat, in which the cystic fibrosis transmembrane conductance regulator gene (CFTR) was knocked out using a pair of zinc finger endonucleases (ZFN). The disrupted Cftr gene carries a 16 base pair deletion in exon 3, resulting in loss of CFTR protein expression. Breeding of heterozygous (CFTR+/−) rats resulted in Mendelian distribution of wild-type, heterozygous, and homozygous (CFTR−/−) pups. Nasal potential difference and transepithelial short circuit current measurements established a robust CF bioelectric phenotype, similar in many respects to that seen in CF patients. Young CFTR−/− rats exhibited histological abnormalities in the ileum and increased intracellular mucus in the proximal nasal septa. By six weeks of age, CFTR−/− males lacked the vas deferens bilaterally. Airway surface liquid and periciliary liquid depth were reduced, and submucosal gland size was abnormal in CFTR−/− animals. Use of ZFN based gene disruption successfully generated a CF animal model that recapitulates many aspects of human disease, and may be useful for modeling other CF genotypes, including CFTR processing defects, premature truncation alleles, and channel gating abnormalities

Multisite Phosphorylation Provides an Effective and Flexible Mechanism for Switch-Like Protein Degradation

Phosphorylation-triggered degradation is a common strategy for elimination of regulatory proteins in many important cell signaling processes. Interesting examples include cyclin-dependent kinase inhibitors such as p27 in human and Sic1 in yeast, which play crucial roles during the G1/S transition in the cell cycle. In this work, we have modeled and analyzed the dynamics of multisite-phosphorylation-triggered protein degradation systematically. Inspired by experimental observations on the Sic1 protein and a previous intriguing theoretical conjecture, we develop a model to examine in detail the degradation dynamics of a protein featuring multiple phosphorylation sites and a threshold site number for elimination in response to a kinase signal. Our model explains the role of multiple phosphorylation sites, compared to a single site, in the regulation of protein degradation. A single-site protein cannot convert a graded input of kinase increase to much sharper output, whereas multisite phosphorylation is capable of generating a highly switch-like temporal profile of the substrate protein with two characteristics: a temporal threshold and rapid decrease beyond the threshold. We introduce a measure termed temporal response coefficient to quantify the extent to which a response in the time domain is switch-like and further investigate how this property is determined by various factors including the kinase input, the total number of sites, the threshold site number for elimination, the order of phosphorylation, the kinetic parameters, and site preference. Some interesting and experimentally verifiable predictions include that the non-degradable fraction of the substrate protein exhibits a more switch-like temporal profile; a sequential system is more switch-like, while a random system has the advantage of increased robustness; all the parameters, including the total number of sites, the threshold site number for elimination and the kinetic parameters synergistically determine the exact extent to which the degradation profile is switch-like. Our results suggest design principles for protein degradation switches which might be a widespread mechanism for precise regulation of cellular processes such as cell cycle progression

Emergency logistics for wildfire suppression based on forecasted disaster evolution

This paper aims to develop a two-layer emergency logistics system with a single depot and multiple demand sites for wildfire suppression and disaster relief. For the first layer, a fire propagation model is first built using both the flame-igniting attributes of wildfires and the factors affecting wildfire propagation and patterns. Second, based on the forecasted propagation behavior, the emergency levels of fire sites in terms of demand on suppression resources are evaluated and prioritized. For the second layer, considering the prioritized fire sites, the corresponding resource allocation problem and vehicle routing problem (VRP) are investigated and addressed. The former is approached using a model that can minimize the total forest loss (from multiple sites) and suppression costs incurred accordingly. This model is constructed and solved using principles of calculus. To address the latter, a multi-objective VRP model is developed to minimize both the travel time and cost of the resource delivery vehicles. A heuristic algorithm is designed to provide the associated solutions of the VRP model. As a result, this paper provides useful insights into effective wildfire suppression by rationalizing resources regarding different fire propagation rates. The supporting models can also be generalized and tailored to tackle logistics resource optimization issues in dynamic operational environments, particularly those sharing the same feature of single supply and multiple demands in logistics planning and operations (e.g., allocation of ambulances and police forces). © 2017 The Author(s

Evaluation of genipin-crosslinked chitosan hydrogels as a potential carrier for silver sulfadiazine nanocrystals

This paper was accepted for publication in the journal Colloids and Surfaces B: Biointerfaces and the definitive published version is available at http://dx.doi.org/10.1016/j.colsurfb.2016.06.016In the present study genipin crosslinked chitosan (CHI) hydrogels, which had been constructed and reported in our previous studies (Lei Gao, et al. Colloids Surf. B Biointerfaces. 2014, 117: 398), were further evaluated for their advantage as a carrier for silver sulfadiazine (AgSD) nanocrystal systems. Firstly, AgSD nanocrystals with a mean particle size of 289 nm were prepared by wet milling method and encapsulated into genipin crosslinked CHI hydrogels. AgSD nanocrystals displayed a uniform distribution and very good physical stability in the hydrogel network. Swelling-dependent release pattern was found for AgSD nanocrystals from hydrogels and the release profile could be well fitted with Peppas equation. When AgSD nanocrystals were encapsulated in hydrogels their fibroblast cytotoxicity decreased markedly, and their antibacterial effects against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were still comparable to unencapsulated AgSD nanocrystals. In vivo evaluation in excision and burn cutaneous wound models in mice showed that AgSD nanocrystal hydrogels markedly decreased the expression of inflammatory cytokine IL-6, but increased the levels of growth factors VEGF-A and TGF-β1. Histopathologically, the wounds treated by hydrogels containing AgSD nanocrystals showed the best healing state compared with commercial AgSD cream, hydrogels containing AgSD bulk powders and blank hydrogels. The wounds treated by AgSD nanocrystal hydrogels were dominated by marked fibroblast proliferation, new blood vessels and thick regenerated epithelial layer. Sirius Red staining assay indicated that AgSD nanocrystal hydrogels resulted in more collagen deposition characterized by a large proportion of type I fibers. Our study suggested that genipin-crosslinked CHI hydrogel was a potential carrier for local antibacterial nanomedicines