Vector measure as controls for explicit nonlinear impulsive system of fed-batch culture

AbstractIn this paper, we consider an optimal control problem of microbial fermentation process in which glycerol is converted to 1,3-propanediol by Klebsiella pneumoniae in fed-batch culture. During the period of reaction, the variation of pH value is monitored to determine glycerol replenishment quantity, guaranteeing that microorganism can always keep growing fast under enough nutrition. Every time pH value is lower than seven, the quantity of glycerol added is such that pH value returns seven again. Glycerol is poured into reactor at discrete time instant and the quantity is controllable. The problem is to determine for each discrete time instant the glycerol quantity to add and maximize the final concentration of 1,3-propanediol. We present a controlled explicit nonlinear impulsive dynamical system of fed-batch culture with state independent vector measures as controls and study the existence, uniqueness, boundedness, continuous dependence and Gâteaux differentiability of its solution with respect to controls. We then propose a multiple objective programming model and demonstrate the regularity of cost functionals and weak compactness of admissible control set. Finally we discuss the existence of optimal control and implement a hybrid particle swarm optimization algorithm to solve the model optimally. Computational results are presented on a numerical example

Modeling nonlinear stochastic kinetic system and stochastic optimal control of microbial bioconversion process in batch culture

In this paper, we analyze a stochastic model representing batch fermentation in the process of glycerol bio-dissimilation to 1,3-propanediol by klebsiella pneumoniae. The stochasticity in the model is introduced by parameter perturbation which is a standard technique in stochastic population modelling. Thus, based on the nonlinear deterministic dynamical system of glycerol bioconversion to 1,3-propanediol in batch culture, we present the stochastic version of the batch fermentation process driven by a five-dimensional Brownian motion and Lipschitz coefficients, which is suitable for the factual fermentation. Subsequently, we study the existence and uniqueness of solutions for the stochastic system as well as the boundedness and Markov property of solutions. Moveover a stochastic optimal control model is constructed and the sufficient and necessary conditions for optimality are proved via dynamic programming principle. Finally we present computer simulation for the stochastic system by using Stochastic Euler–Maruyama scheme. Compared with the results from the deterministic system, numerical results reveal the peculiar role of stochasticity in the dynamical responses of the batch culture

Somatic mutations in FAT cadherin family members constitute an underrecognized subtype of colorectal adenocarcinoma with unique clinicopathologic features

BACKGROUND: The FAT cadherin family members (FAT1, FAT2, FAT3 and FAT4) are conserved tumor suppressors that are recurrently mutated in several types of human cancers, including colorectal carcinoma (CRC). AIM: To characterize the clinicopathologic features of CRC patients with somatic mutations in FAT cadherin family members. METHODS: We analyzed 526 CRC cases from The Cancer Genome Atlas PanCancer Atlas dataset. CRC samples were subclassified into 2 groups based on the presence or absence of somatic mutations in RESULTS: This CRC study cohort had frequent mutations in the CONCLUSION

Expressions and clinic significance of miRNA-143, miRNA- 34A, miRNA-944, miRNA-101 and miRNA-218 in cervical cancer tissues

Purpose: To search for novel biomarkers for early diagnosis of cervical cancer, as well as novel therapeutic target for cervical cancer.Methods: A total of 96 cervical tissue specimens were collected from patients in the Second Affiliated Hospital of Zhengzhou University, out of which 10 were normal control. The remaining specimens (86) were cervical cancer specimens and were divided into 4 groups (A - D) based on tumor-biomarker levels of CA125 and SCC. Quantitative real-time polymerase chain reaction technology (qRT-PCR) was used to detect the expressions of miRNA-143, miRNA-34A, miRNA-944, miRNA-101 and miRNA-218 in the cervical cancer tissues.Results: The levels of CA125 (U/mL) and SCC (ug/L) expressed in normal control group and groups A - D were 11.75 and 0.73 (n = 10), 382 and 2.72 (n = 25), 912.9 and 3.93 (n = 21), 1675 and 5.87 (n = 29), and 2120 and 6.66 (n = 11), respectively. Furthermore, qRT-PCR results showed that the expressions of miRNA-944 and miRNA-218 in cervical cancer tissues were markedly up-regulated compared to normal control tissues (p < 0.01). In contrast, the expression level of miRNA-143, miRNA-34A, and miRNA-101 were significantly decreased (p < 0.01).Conclusion: The biomarkers, miRNA-143, miRNA-34A, miRNA-944, miRNA-101 and miRNA-218, can be considered novel for early diagnosis of cervical cancer.Keywords: Cervical cancer, Biomarkers, miRNA-143, miRNA-34A, miRNA-944, miRNA-101, miRNA- 21

α-Tocopheryl succinate inhibits angiogenesis by disrupting paracrine FGF2 signalling

AbstractMalignant mesothelioma (MM) cells enhanced proliferation of endothelial cells (ECs) as well as their angiogenesis in vitro by secretion of fibroblast growth factor-2 (FGF2). This effect was suppressed by pre-treating MM cells with α-tocopheryl succinate (α-TOS), which inhibited FGF2 secretion by inducing mitochondria-dependent generation of reactive oxygen species. The role of FGF2 was confirmed by its down-regulation by treating MM cells with siRNA, abolishing EC proliferation and wound healing enhancement afforded by MM cells. We conclude that α-TOS disrupts angiogenesis mediated by MM cells by inhibiting FGF2 paracrine signalling

Diaqua­bis­[5-(2-pyridyl­meth­yl)tetra­zol­ato-κ2 N 1,N 5]zinc(II)

In the title mononuclear complex, [Zn(C7H6N5)2(H2O)2], the ZnII atom, located on an inversion centre, is in a distorted octa­hedral coordination geometry formed by four N atoms from two chelating 5-(2-pyridyl­meth­yl)tetra­zolate ligands and two O donors from two water mol­ecules. Inter­molecular O—H⋯N hydrogen bonds between the coordinated water mol­ecule and the tetra­zolyl group of the 5-(2-pyridyl­meth­yl)tetra­zolate ligand lead to the formation of a three-dimensional network

Single cell epigenomic and transcriptomic analysis uncovers potential transcription factors regulating mitotic/meiotic switch

In order to reveal the complex mechanism governing the mitotic/meiotic switch in female germ cells at epigenomic and genomic levels, we examined the chromatin accessibility (scATAC-seq) and the transcriptional dynamics (scRNA-seq) in germ cells of mouse embryonic ovary between E11.5 to 13.5 at single-cell resolution. Adopting a strict transcription factors (TFs) screening framework that makes it easier to understand the single-cell chromatin signature and a TF interaction algorithm that integrates the transcript levels, chromatin accessibility, and motif scores, we identified 14 TFs potentially regulating the mitotic/meiotic switch, including TCFL5, E2F1, E2F2, E2F6, E2F8, BATF3, SP1, FOS, FOXN3, VEZF1, GBX2, CEBPG, JUND, and TFDP1. Focusing on TCFL5, we constructed Tcfl5(+/-) mice which showed significantly reduced fertility and found that decreasing TCFL5 expression in cultured E12.5 ovaries by RNAi impaired meiotic progression from leptotene to zygotene. Bioinformatics analysis of published results of the embryonic germ cell transcriptome and the finding that in these cells central meiotic genes (Stra8, Tcfl5, Sycp3, and E2f2) possess open chromatin status already at the mitotic stage together with other features of TCFL5 (potential capability to interact with core TFs and activate meiotic genes, its progressive activation after preleptotene, binding sites in the promoter region of E2f2 and Sycp3), indicated extensive amplification of transcriptional programs associated to mitotic/meiotic switch with an important contribution of TCFL5. We conclude that the identified TFs, are involved in various stages of the mitotic/meiotic switch in female germ cells, TCFL5 primarily in meiotic progression. Further investigation on these factors might give a significant contribution to unravel the molecular mechanisms of this fundamental process of oogenesis and provide clues about pathologies in women such as primary ovarian insufficiency (POI) due at least in part to meiotic defects

{μ-trans-N,N′-Bis[(diphenyl­phosphan­yl)meth­yl]benzene-1,4-diamine-κ2 P:P′}bis­{(acetonitrile-κN)[dipyrido[3,2-a:2′,3′-c]phenazine-κ2 N 4,N 5]copper(I)} bis­(tetra­fluoridoborate)

In the centrosymmetric dinuclear title compound, [Cu2(C2H3N)2(C18H10N4)2(C32H30N2P2)](BF4)2, the CuI centre is coordinated by two N atoms from a dipyridophenazine ligand, one P atom from an N,N′-bis­[(diphenyl­phosphan­yl)meth­yl]benzene-1,4-diamine (bpbda) ligand, and one N atom from an acetonitrile mol­ecule in a distorted tetra­hedral geometry. The bpbda ligand, lying on an inversion center, bridges two CuI centres into a Z-shaped complex. Intra­molecular π–π inter­actions between the dipyridophenazine ligand and the benzene ring of the bpbda ligand are observed [centroid–centroid distance = 3.459 (3) Å]. The crystal structure also involves inter­molecular π–π inter­actions between the dipyridophenazine ligands [centroid–centroid distance = 3.506 (3) Å], which lead to a one-dimensional supra­molecular structure