A new stochastic and state space model of human colon cancer incorporating multiple pathways

<p>Abstract</p> <p>Background and Purpose</p> <p>Studies by molecular biologists and geneticists have shown that tumors of human colon cancer are developed from colon stem cells through two mechanisms: The chromosomal instability and the micro-satellite instability. The purpose of this paper is therefore to develop a new stochastic and state space model for carcinogenesis of human colon cancer incorporating these biological mechanisms.</p> <p>Results</p> <p>Based on recent biological studies, in this paper we have developed a state space model for human colon cancer. In this state space model, the stochastic system is represented by a stochastic model, involving 2 different pathways-the chromosomal instability pathway and the micro-satellite instability pathway; the observation, cancer incidence data, is represented by a statistical model. Based on this model we have developed a generalized Bayesian approach to estimate the parameters through the posterior modes of the parameters via Gibbs sampling procedures. We have applied this model to fit and analyze the SEER data of human colon cancers from NCI/NIH.</p> <p>Conclusions</p> <p>Our results indicate that the model not only provides a logical avenue to incorporate biological information but also fits the data much better than other models including the 4-stage single pathway model. This model not only would provide more insights into human colon cancer but also would provide useful guidance for its prevention and control and for prediction of future cancer cases.</p> <p>Reviewers</p> <p>This article was reviewed by M.P. Little and M. Kimmel</p

Correlation of Plasma MMP-1 and TIMP-1 Levels and the Colonic Mucosa Expressions in Patients with Ulcerative Colitis

Background. Both plasma and mucosal levels of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) have been shown to be independently correlated with ulcerative colitis (UC), but their relationship with each other and to disease severity remains unclear. This study aims to evaluate the relationship between colonic mucosal and plasma levels of MMP-1 and TIMP-1 with each other and with the severity of ulcerative colitis (UC). Methods. Colonic mucosal lesions and venous blood samples were collected from 30 patients with UC and 15 normal subjects. Real-time reverse transcription-PCR and immunohistochemistry were used to determine colonic mucosal MMP-1 and TIMP-1 expression; ELISA was used to measure plasma levels of MMP-1 and TIMP-1. Results. Expression of colonic mucosal and plasma MMP-1 and TIMP-1 in patients with UC was significantly higher than that of controls (P < .05), and was positively correlated with disease severity (P < .05). Plasma MMP-1 and TIMP-1 levels were well correlated with their corresponding expression in colonic mucosa (P < .05, r = 0.805 and 0.908). Conclusion. Plasma MMP-1 and TIMP-1 levels reflect their colonic mucosal expression to some extent in patients with UC. Plasma MMP-1 and TIMP-1, in particular, demonstrate the potential to become biomarkers to clinically diagnose UC, predict its severity, and guide further therapy

(Sulfasalazinato-κO)bis­(triphenyl­phosphine-κP)copper(I)

The title mixed-ligand copper(I) complex, [Cu(C18H13N4O5S)(C18H15P)2], was synthesized via solvothermal reaction of [Cu(PPh3)2(MeCN)2]ClO4 and sulfasalazine [systematic name: 2-hydr­oxy-5-(2-{4-[(2-pyridylamino)sulfon­yl]phen­yl}diazen­yl)benzoic acid]. The mononuclear complex displays a trigonal coordination geometry for the Cu(I) atom, which is surrounded by two P-atom donors from two different PPh3 ligands and one O-atom donor from the monodentate carboxyl­ate group of the sulfasalazinate ligand. The latter ligand is found in a zwitterionic form, with a deprotonated amine N atom and a protonated pyridine N atom. Such a feature was previously described for free sulfasalazine. The crystal structure is stabilized by C—H⋯O, C—H⋯N, N—H⋯N and O—H⋯O hydrogen bonds

Robo signaling regulates the production of cranial neural crest cells

Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1+ cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development

Improvements to enhance robustness of third-order scale-independent WENO-Z schemes

Although there are many improvements to WENO3-Z that target the achievement of optimal order in the occurrence of the first-order critical point (CP1), they mainly address resolution performance, while the robustness of schemes is of less concern and lacks understanding accordingly. In light of our analysis considering the occurrence of critical points within grid intervals, we theoretically prove that it is impossible for a scale-independent scheme that has the stencil of WENO3-Z to fulfill the above order achievement, and current scale-dependent improvements barely fulfill the job when CP1 occurs at the middle of the grid cell. In order to achieve scale-independent improvements, we devise new smoothness indicators that increase the error order from 2 to 4 when CP1 occurs and perform more stably. Meanwhile, we construct a new global smoothness indicator that increases the error order from 4 to 5 similarly, through which new nonlinear weights with regard to WENO3-Z are derived and new scale-independents improvements, namely WENO-ZES2 and -ZES3, are acquired. Through 1D scalar and Euler tests, as well as 2D computations, in comparison with typical scale-dependent improvement, the following performances of the proposed schemes are demonstrated: The schemes can achieve third-order accuracy at CP1 no matter its location in the stencil, indicate high resolution in resolving flow subtleties, and manifest strong robustness in hypersonic simulations (e.g., the accomplishment of computations on hypersonic half-cylinder flow with Mach numbers reaching 16 and 19, respectively, as well as essentially non-oscillatory solutions of inviscid sharp double cone flow at M=9.59), which contrasts the comparative WENO3-Z improvement

4-(2,4-Dichloro­phen­yl)-5,5-dimethyl-2-(3-silatranyl­propyl­mino)-1,3,2-dioxa­phospho­rinane 2-oxide

In the title compound, C20H31Cl2N2O6PSi, the dioxaphospho­rinane ring adopts a cis conformation. The silatrane fragment forms a cage-like structure in which there exists an intra­molecular Si—N donor–acceptor bond. In the crystal, centrosymmetrically related mol­ecules are linked by pairs of N—H⋯O hydrogen bonds into inversion dimers, generating rings with graph-set motif R 2 2(8). The dimers are further connected into ribbons parallel to the a axis by inter­molecular C—H⋯O hydrogen bonds