Finding stationary solutions to the chemical master equation by gluing state spaces at one or two states recursively

Noise is indispensible to key cellular activities, including gene expression coordination and probabilistic differentiation. Stochastic models, such as the chemical master equation (CME), are essential to model noise in the levels of cellular components. In the CME framework, each state is associated with the molecular counts of all component species, and specifies the probability for the system to have that set of molecular counts. Analytic solutions to the CME are rarely known but can bring exciting benefits. For instance, simulations of biochemical reaction networks that are multiscale in time can be sped up tremendously by incorporating analytic solutions of the slow time-scale dynamics. Analytic solutions also enable the design of stationary distributions with properties such as the modality of the distribution, the mean expression level, and the level of noise. One way to derive the analytic steady state response of a biochemical reaction network was recently proposed by (Mélykúti et al. 2014). The paper recursively glues simple state spaces together, for which we have analytic solutions, at one or two states. In this work, we explore the benefits and limitations of the gluing technique proposed by Mélykúti et al., and introduce recursive algorithms that use the technique to solve for the analytic steady state response of stochastic biochemical reaction networks. We give formal characterizations of the set of reaction networks whose state spaces can be obtained by carrying out single-point gluing of paths, cycles or both sequentially. We find that the dimension of the state space of a reaction network equals the maximum number of linearly independent reactions in the system. We then characterize the complete set of stochastic biochemical reaction networks that have elementary reactions and two-dimensional state spaces. As an example, we propose a recursive algorithm that uses the gluing technique to solve for the steady state response of a mass-conserving system with two connected monomolecular reversible reactions. Even though the gluing technique can only construct finite state spaces, we find that, by taking the size of a finite state space to infinity, the steady state response can converge to the analytic solution on the resulting infinite state space. Finally, we illustrate the aforementioned ideas with the example of two interconnected transcriptional components, which was first studied by (Ghaemi and Del Vecchio 2012)

NADPH oxidase 4 mediates insulin-stimulated HIF-1α and VEGF expression, and angiogenesis in vitro

Acute intensive insulin therapy causes a transient worsening of diabetic retinopathy in type 1 diabetes patients and is related to VEGF expression. Reactive oxygen species (ROS) have been shown to be involved in HIF-1α and VEGF expression induced by insulin, but the role of specific ROS sources has not been fully elucidated. In this study we examined the role of NADPH oxidase subunit 4 (Nox4) in insulin-stimulated HIF-1α and VEGF expression, and angiogenic responses in human microvascular endothelial cells (HMVECs). Here we demonstrate that knockdown of Nox4 by siRNA reduced insulin-stimulated ROS generation, the tyrosine phosphorylation of IR-β and IRS-1, but did not change the serine phosphorylation of IRS-1. Nox4 gene silencing had a much greater inhibitory effect on insulin-induced AKT activation than ERK1/2 activation, whereas it had little effect on the expression of the phosphatases such as MKP-1 and SHIP. Inhibition of Nox4 expression inhibited the transcriptional activity of VEGF through HIF-1. Overexpression of wild-type Nox4 was sufficient to increase VEGF transcriptional activity, and further enhanced insulin-stimulated the activation of VEGF. Downregulation of Nox4 expression decreased insulin-stimulated mRNA and protein expression of HIF-1α, but did not change the rate of HIF-1α degradation. Inhibition of Nox4 impaired insulin-stimulated VEGF expression, cell migration, cell proliferation, and tube formation in HMVECs. Our data indicate that Nox4-derived ROS are essential for HIF-1α-dependent VEGF expression, and angiogenesis in vitro induced by insulin. Nox4 may be an attractive therapeutic target for diabetic retinopathy caused by intensive insulin treatment

Pendugaan Model Permintaan Ubi Kayu di Indonesia

Cassava (Manihot esculenta Crantz) is important commodity of Indonesia not only as forth producer after Nigeria, Thailand, and Brazil but also as source of carbohydrate. This research will use time series data among 1999-2009. The increasing of cassava production along 1971-2009 reaching 22,03 million tons. And also the projection until 2010 increase until 25,54 million tons. By this increasing, it is expected can open fissure of production and marketing in Indonesia better than before. Simultaneously test of variable contained the coming of cassava stock, another demand, cassava export, cassava consumption, and the demand of cassava last year has significant effect toward cassava demand

Peran Praktisi Dalam Pengembangan Teori Dan Proses Pembelajaran Untuk Sekolah Bisnis

The decreasing number of intakes and quality of the students, and crisis identityhave jeopardise the survival of business schools. There must be a breakthrough toovercome these hard situation. One of the solution is theories-in-use approach, whichis needed to develop the appropriate theory. The writer also suggests to recruit practitionersas the faculty members. This will encourage original theories developmentwhich is appropriate for third world countries like Indonesia. The other solutionis to send the existing lecturers to join the consulting and encourage them to havethe knowledge of practice world. By doing these, hopefully better condition will beachieved

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Association of HOTAIR expression with PI3K/Akt pathway activation in adenocarcinoma of esophagogastric junction

Although the Hox transcript antisense intergenic RNA (HOTAIR), a vital long non-coding RNA, is known to participate in the development and progression of a wide range of carcinomas, there are still no published reports regarding its expression in adenocarcinoma of esophagogastric junction (AEJ). The aims of this study were to investigate the expression of HOTAIR, and to analyze the association of its expression with PI3K/Akt pathway activation in clinical AEJ patients

An Investigation of the High Efficiency Estimation Approach of the Large-Scale Scattered Point Cloud Normal Vector

The normal vector estimation of the large-scale scattered point cloud (LSSPC) plays an important role in point-based shape editing. However, the normal vector estimation for LSSPC cannot meet the great challenge of the sharp increase of the point cloud that is mainly attributed to its low computational efficiency. In this paper, a novel, fast method-based on bi-linear interpolation is reported on the normal vector estimation for LSSPC. We divide the point sets into many small cubes to speed up the local point search and construct interpolation nodes on the isosurface expressed by the point cloud. On the premise of calculating the normal vectors of these interpolated nodes, a normal vector bi-linear interpolation of the points in the cube is realized. The proposed approach has the merits of accurate, simple, and high efficiency, because the algorithm only needs to search neighbor and calculates normal vectors for interpolation nodes that are usually far less than the point cloud. The experimental results of several real and simulated point sets show that our method is over three times faster than the Elliptic Gabriel Graph-based method, and the average deviation is less than 0.01 mm

Financial Risk Prevention Model of Financial Institutions Based on Linear Partial Differential Equation

The financial risk early warning model is an effective means of risk prevention. This paper’s linear partial differential equation is innovatively applied to financial institutions’ financial risk early warning system. At the same time, we construct a partial differential equation, linear discriminant model, based on the extreme value principle. The system can effectively avoid the problem of fractional model failure. The simulation results show that the algorithm in this paper improves the accuracy and speed of financial risk early warning and significantly reduces the two-class classification error rate of the model