Differential responses of normal human coronary artery endothelial cells against multiple cytokines comparatively assessed by gene expression profiles

AbstractEndothelial cells play an important role in terms of biological functions by responding to a variety of stimuli in the blood. However, little is known about the molecular mechanism involved in rendering the variety in the cellular response. To investigate the variety of the cellular responses against exogenous stimuli at the gene expression level, we attempted to describe the cellular responses with comprehensive gene expression profiles, dissect them into multiple response patterns, and characterize the response patterns according to the information accumulated so far on the genes included in the patterns. We comparatively analyzed in parallel the gene expression profiles obtained with DNA microarrays from normal human coronary artery endothelial cells (HCAECs) stimulated with multiple cytokines, interleukin-1β, tumor necrosis factor-α, interferon-β, interferon-γ, and oncostatin M, which are profoundly involved in various functional responses of endothelial cells. These analyses revealed that the cellular responses of HCAECs against these cytokines included at least 15 response patterns specific to a single cytokine or common to multiple cytokines. Moreover, we statistically extracted genes contained within the individual response patterns and characterized the response patterns with the genes referring to the previously accumulated findings including the biological process defined by the Gene Ontology Consortium (GO). Out of the 15 response patterns in which at least one gene was successfully extracted through the statistical approach, 11 response patterns were differentially characterized by representing the number of genes contained in individual criteria of the biological process in the GO only. The approach to dissect cellular responses into response patterns and to characterize the pattern at the gene expression level may contribute to the gaining of insight for untangling the diversity of cellular functions

A Method to Measure Visual Field Sensitivity at the Edges of Glaucomatous Scotomata

METHODS. Subjects comprised 22 glaucomatous patients. Gradients of sensitivity were calculated for ''squares'' of test points in a patient's 24-2/30-2 VF results, so that the edges of scotomata could be identified where gradients were steep. Next, 10 new VF points were placed in these locations for each patient. Each patient's VF was then measured using this novel test grid (52 standard 24-2 test points and 10 additional points examined concurrently) on two separate occasions. The absolute difference between the measured sensitivity at each new additional test point and the average of the sensitivities of its surrounding four test points was calculated (D ave ). The intra-and intervisit reproducibility of the additional test points' thresholds was calculated. Finally, fluctuation of overall VF damage was estimated using the intraclass correlation coefficient (ICC) and the coefficient of variation (CV). RESULTS. The average of the sensitivities (D ave ) increased as the gradient of the plane steepened, whereas the reproducibility of the additional test points' thresholds remained stable. ICC was significantly higher and CV was significantly lower for the novel test grid compared with the standard 24-2 test pattern. CONCLUSIONS. It may be advantageous to increase the density of VF test points where there are large local differences in VF sensitivity. These additional measurements may result in more reproducible and well-defined estimates of scotomata

The E3 Ubiquitin Ligase Activity of Trip12 Is Essential for Mouse Embryogenesis

Protein ubiquitination is a post-translational protein modification that regulates many biological conditions [1], [2], [3], [4]. Trip12 is a HECT-type E3 ubiquitin ligase that ubiquitinates ARF and APP-BP1 [5], [6]. However, the significance of Trip12 in vivo is largely unknown. Here we show that the ubiquitin ligase activity of Trip12 is indispensable for mouse embryogenesis. A homozygous mutation in Trip12 (Trip12mt/mt) that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development. Trip12mt/mt embryos exhibited growth arrest and increased expression of the negative cell cycle regulator p16 [7], [8], [9], [10]. In contrast, Trip12mt/mt ES cells were viable. They had decreased proliferation, but maintained both the undifferentiated state and the ability to differentiate. Trip12mt/mt ES cells had increased levels of the BAF57 protein (a component of the SWI/SNF chromatin remodeling complex) and altered gene expression patterns. These data suggest that Trip12 is involved in global gene expression and plays an important role in mouse development

Fundamental electron-transfer and proton-coupled electron-transfer properties of Ru(iv)-oxo complexes

Isolation and characterisation of Ru-IV(O) complexes were accomplished to investigate their fundamental electron transfer (ET) and proton-coupled ET (PCET) properties. Reorganisation energies (lambda) in electron transfer (ET) and proton-coupled ET (PCET) from electron donors to the isolated Ru-IV(O) complexes have been determined for the first time to be in the range of 1.70-1.88 eV (ET) and 1.20-1.26 eV (PCET). It was suggested that the reduction of the lambda values of PCET in comparison with those of ET should be due to the smaller structural change in PCET than that in ET on the basis of DFT calculations on 1 and 1e(-)-reduced 1 in the absence and presence of TFA, respectively. In addition, the smaller lambda values for the Ru-IV(O) complexes than those reported for Fe-IV(O) and Mn-IV(O) complexes should be due to the lack of participation of d(sigma) orbitals in the ET and PCET reactions. This is the first example to evaluate fundamental ET and PCET properties of Ru-IV(O) complexes leading to further understanding of their reactivity in oxidation reactions

高精度逆コレスキー分解アルゴリズムの収束解析に関する研究

早大学位記番号:新7127早稲田大

SHIFTED CHOLESKY QR FOR COMPUTING THE QR FACTORIZATION OF ILL-CONDITIONED MATRICES

The Cholesky QR algorithm is an efficient communication-minimizing algorithm for computing the QR factorization of a tall-skinny matrix X epsilon R-mxn, where m >> n. Unfortunately it is inherently unstable and often breaks down when the matrix is ill-conditioned. A recent work [Yamamoto et al., ETNA, 44, pp. 306--326 (2015)] establishes that the instability can be cured by repeating the algorithm twice (called CholeskyQR2). However, the applicability of CholeskyQR2 is still limited by the requirement that the Cholesky factorization of the Gram matrix X-inverted perpendicular X runs to completion, which means that it does not always work for matrices X with the 2-norm condition number kappa(2)(X) roughly greater than u(-1/2), where u is the unit roundoff. In this work we extend the applicability to kappa(2)(X) = O (u(-1)) by introducing a shift to the computed Gram matrix so as to guarantee the Cholesky factorization R-inverted perpendicular R = A(inverted perpendicular) A+sI succeeds numerically. We show that the computed AR(-1) has reduced condition number that is roughly bounded by u(-1/2), for which CholeskyQR2 safely computes the QR factorization, yielding a computed Q of orthogonality vertical bar vertical bar Q(inverted perpendicular) - Q I vertical bar vertical bar(2) and residual vertical bar vertical bar A - QR vertical bar vertical bar(F) / vertical bar vertical bar A vertical bar vertical bar(F) both of the order of u. Thus we obtain the required QR factorization by essentially running Cholesky QR thrice. We extensively analyze the resulting algorithm shiftedCholeskyQR3 to reveal its excellent numerical stability. The shiftedCholeskyQR3 algorithm is also highly parallelizable, and applicable and effective also when working with an oblique inner product. We illustrate our findings through experiments, in which we achieve significant speedup over alternative methods