An Iterative Method for Optimal Feedback Control and Generalized HJB Equation

In this paper, a new iterative method is proposed to solve the generalized Hamilton-Jacobi-Bellman(GHJB) equation through successively approximate it. Firstly, the GHJB equation is converted to an algebraic equation with the vector norm,which is essentially a set of simultaneous nonlinear equations in the case of dynamic systems. Then, the proposed algorithm solves GHJB equation numerically for points near the origin by considering the linearization of the non-linear equations under a good initial control guess. Finally, the procedure is proved to converge to the optimal stabilizing solution with respect to the iteration variable. In addition, it is shown that the result is a closed-loop control based on this iterative approach. Illustrative examples show that the update control laws will converge to optimal control for nonlinear systems.

The Frequency of Infectious Diseases in Manzhouli Port from 2012 to 2014

The aim of this study was to determine the frequency of infectious diseases among people entering/exiting via Manzhouli port. We analyzed infectious disease data from the Manzhouli International Travel Health care Center covering 2012 through 2014, as well as performed several laboratory tests to measure rates of infection. The frequencies of infectious diseases as well as their association with occupation and year of occurrence were calculated for people entering and exiting via the port. The total proportion of infectious diseases measured was 2.18%. Hepatitis B was the most commonly occurring at 1.68%, followed by syphilis, hepatits C and HIV, which were 0.23%, 0.21% and 0.04%, respectively. Contract workers, traffic staff, foreigners and those married abroad were more likely to be infected. Furthermore, there were significant differences among three years. Strategies should be developed and preventive policies should be implemented aimed at protecting the at risk populations at Manzhouli port, especially with regard to contract workers, traffic staff, foreigners and those married abroad.

Cytoplasmic YAP1-mediated ESCRT-III assembly promotes autophagic cell death and is ubiquitinated by NEDD4L in breast cancer

Background:Nuclear Yes1-associated transcriptional regulator(YAP1)promotes tumor progression.However,the function of cytoplasmic YAP1 in breast cancer cells and its impact on the survival of breast cancer patients remain unclear.Our research aimed to explore the biological function of cytoplasmic YAP1 in breast cancer cells and the possibility of cytoplasmic YAP1 as a predictive marker of breast cancer survival.Methods:We constructed cell mutant models,including NLS-YAP15SA(nuclear localized),YAP1S94A(incapable of binding to the TEA domain transcription factor family)and YAP1S127D(cytoplasmic localized),and used Cell Counting Kit-8(CCK-8)assays,5-ethynyl-2’-deoxyuridine(EdU)incorporation assays,and Western blotting(WB)analysis to detect cell proliferation and apoptosis.The specific mechanism of cytoplasmic YAP1-mediated endosomal sorting complexes required for transport III(ESCRT-III)assembly was studied by co-immunoprecipitation,immunofluorescence staining,and WB analysis.Epigallocatechin gallate(EGCG)was used to simulate YAP1 retention in the cytoplasm in in vitro and in vivo experiments to study the function of cytoplasmic YAP1.YAP1 binding to NEDD4-like E3 ubiquitin protein ligase(NEDD4L)was identified using mass spectrometry and was verified in vitro.Breast tissue microarrays were used to analyze the relationship between cytoplasmic YAP1 expression and the survival of breast cancer patients.Results:YAP1 was mainly expressed in the cytoplasm in breast cancer cells.Cytoplasmic YAP1 promoted autophagic death of breast cancer cells.Cytoplasmic YAP1 bound to the ESCRT-III complex subunits charged multivesicular body protein 2B(CHMP2B)and vacuolar protein sorting 4 homolog B(VPS4B),promoting assembly of CHMP2B-VPS4B and activating autophagosome formation.EGCG retained YAP1 in the cytoplasm,promoting the assembly of CHMP2B-VPS4B to promote autophagic death of breast cancer cells.YAP1 bound to NEDD4L,and NEDD4L mediated ubiquitination and degradation of YAP1.Breast tissue microarrays revealed that high levels of cytoplasmic YAP1 were beneficial to the survival of breast cancer patients.Conclusions:Cytoplasmic YAP1 mediated autophagic death of breast cancer cells by promoting assembly of the ESCRT-III complex;furthermore,we established a new breast cancer survival prediction model based on cytoplasmic YAP1 expression.

Shared Gene Regulation during Human Somatic Cell Reprogramming

Human induced pluripotent stem （iPS） cells have the ability to differentiate into all somatic cells and to maintain unlimited self- renewal. Therefore, they have great potential in both basic research and clinical therapy for many diseases. To identify potentially universal mechanisms of human somatic cell reprogramming, we studied gene expression changes in three types of cells undergoing reprogramming. The set of 570 genes commonly regulated during induction of iPS cells includes known embryonic stem （ES） cell markers and pluripotency related genes. We also identified novel genes and biological categories which may be related to somatic cell reprogramming. For example, some of the down-regulated genes are predicted targets of the pluripotency microRNA cluster miR302/367, and the proteins from these putative target genes interact with the stem cell pluripotency factor POU5F1 according to our network analysis. Our results identified candidate gene sets to guide research on the mechanisms operating during somatic cell reprogramming.

IFN-inducible p47 GTPases display differential responses to Schistosoma japonicum acute infection

Interferon gamma induced GTPase(IGTP)(also named lrgm3)and interferon gamma inducible protein 47(IRG-47)(also named lIrgd)are interferon(IFN)-inducible p47 GTPases that have been shown to regulate host resistance to intracellular pathogens.Little knowledge has been known about the role of p47 GTPases in host responses against extracellular pathogens.To investigate possible roles of IGTP and IRG-47 in the course of Schistosoma japonicum infection,IGTP and IRG-47 knockout and wild-type(WT)mice were challenged with cercariae of S.japonicum,and host responses were analyzed.At the acute stage of S.japonicum infection,mice that lacked IGTP displayed similar parasite burden and pathological damage to WT mice.Importantly,S.japonicum-infected lRG-47-deficient mice,in contrast to IGTP-deficient mice and WT mice,showed significantly reduced worms and lower egg-burden,but intense granulomatous reaction evoked by schistosome eggs in peripheral parts of liver lobes.In addition,upregulation of inflammation-related gene expression was observed in the spleen of IRG-47-deficient mice using oligonucleotide microarrays,in which multiple pathways of cytokine-cytokine receptor interaction,T-cell receptor signaling,complement,coagulation cascades and cell adhesion molecules were highlighted.Taken together,these data suggest that IGTP and IRG-47 might have distinct features that were differentially required for resistance to S.japonicum.

Directed hepatic differentiation from embryonic stem cells

The liver is the largest internal organ in mammals,and is important for the maintenance of normal physiological functions of other tissues and organs.Hepatitis,cirrhosis,liver cancer and other chronic liver diseases are serious threats to human health,and these problems are compounded by a scarcity of liver donors for transplantation therapies.Directed differentiation of embryonic stem cells to liver cells is a promising strategy for obtaining hepatocytes that can be used for cell transplantation.In vitro hepatocyte differentiation of embryonic stem cells requires a profound understanding of normal development during embryonic hepatogenesis.Here we provide a simple description of hepatogenesis in vivo and discuss directed differentiation of embryonic stem cells into hepatocytes in vitro.