Robustness and modular design of the Drosophila segment polarity network

Biomolecular networks have to perform their functions robustly. A robust function may have preferences in the topological structures of the underlying network. We carried out an exhaustive computational analysis on network topologies in relation to a patterning function in Drosophila embryogenesis. We found that while the vast majority of topologies can either not perform the required function or only do so very fragilely, a small fraction of topologies emerges as particularly robust for the function. The topology adopted by Drosophila, that of the segment polarity network, is a top ranking one among all topologies with no direct autoregulation. Furthermore, we found that all robust topologies are modular--each being a combination of three kinds of modules. These modules can be traced back to three sub-functions of the patterning function and their combinations provide a combinatorial variability for the robust topologies. Our results suggest that the requirement of functional robustness drastically reduces the choices of viable topology to a limited set of modular combinations among which nature optimizes its choice under evolutionary and other biological constraints.Comment: Supplementary Information and Synopsis available at http://www.ucsf.edu/tanglab

Helical tomotherapy for advanced esophageal cancer improves target conformity and homogeneity: A comparison with fixed-field intensity-modulated radiotherapy

Purpose: To evaluate the usefulness of helical tomotherapy (HT) in the treatment of advanced esophageal cancer (EC) and compare target homogeneity, conformity and normal tissue doses between HT and fixed-field intensity-modulated radiotherapy (ff-IMRT). Methods: In all, 23 patients with cT3-4N0-1M0-1a thoracic EC (upper esophagus, 9 patients; middle esophagus, 6; distal esophagus, 6 and esophagogastric junction, 2) who were treated with ff-IMRT (60 Gy in 30 fractions) were re-planned for HT and ff-IMRT with the same clinical require­ments. Comparisons were performed using the Wilcoxon matched-pair signed-rank test. Results: Compared with ff-IMRT, HT significantly reduced the homogeneity index for thoracic, upper, middle and distal ECs by 38%, 31%, 36% and 33%, respectively (P < 0.05). The conformity index was increased by HT for thoracic, upper and middle ECs by 9%, 9% and 18%, respectively (P < 0.05). Target coverage was improved by 1% with HT (P < 0.05). The mean lung dose was significantly reduced by HT for thoracic and upper ECs (P < 0.05). The V20 (volume receiving at least 20 Gy) and higher dose volumes of the lungs were decreased by HT in all cases, but the differences were significant for thoracic, upper and distal ECs (P < 0.05), with reductions of 2.1%, 3.1% and 2.2%, respectively. HT resulted in a larger lung V5 for thoracic, upper, middle and distal ECs, with increases of 3.5%, 1.5%, 7.2% and 3.2%, respectively. Heart sparing was significantly better with HT than with ff-IMRT in terms of the V30 and V40 for thoracic, upper, middle and distal ECs (P < 0.05). Conclusions: Compared to ff-IMRT, HT provides superior target coverage, conformity and homogeneity, with reduced the volume of high doses to the lungs and heart for advanced EC. HT may be a treatment option for advanced EC, especially upper EC

Combinatorial Pattern Discovery Approach for the Folding Trajectory Analysis of a β-Hairpin

The study of protein folding mechanisms continues to be one of the most challenging problems in computational biology. Currently, the protein folding mechanism is often characterized by calculating the free energy landscape versus various reaction coordinates, such as the fraction of native contacts, the radius of gyration, RMSD from the native structure, and so on. In this paper, we present a combinatorial pattern discovery approach toward understanding the global state changes during the folding process. This is a first step toward an unsupervised (and perhaps eventually automated) approach toward identification of global states. The approach is based on computing biclusters (or patterned clusters)—each cluster is a combination of various reaction coordinates, and its signature pattern facilitates the computation of the Z-score for the cluster. For this discovery process, we present an algorithm of time complexity c∈RO((N + nm) log n), where N is the size of the output patterns and (n × m) is the size of the input with n time frames and m reaction coordinates. To date, this is the best time complexity for this problem. We next apply this to a β-hairpin folding trajectory and demonstrate that this approach extracts crucial information about protein folding intermediate states and mechanism. We make three observations about the approach: (1) The method recovers states previously obtained by visually analyzing free energy surfaces. (2) It also succeeds in extracting meaningful patterns and structures that had been overlooked in previous works, which provides a better understanding of the folding mechanism of the β-hairpin. These new patterns also interconnect various states in existing free energy surfaces versus different reaction coordinates. (3) The approach does not require calculating the free energy values, yet it offers an analysis comparable to, and sometimes better than, the methods that use free energy landscapes, thus validating the choice of reaction coordinates. (An abstract version of this work was presented at the 2005 Asia Pacific Bioinformatics Conference [1].

Environmental controls on coral skeletal δ13C in the northern South China Sea

In this paper, we investigate the relationship between seasonal climatic and environmental variables, and the skeletal δC of modern and mid-Holocene Porites lutea corals from the southern coast of Hainan Island in the northern South China Sea. No significant correlations were observed between δC in the modern coral and solar insolation or sea surface temperature. However, seasonal variability of δC in the modern coral covaries with rainfall on Hainan Island. Furthermore, the seasonal variations of δC in both the modern and mid-Holocene coral are synchronous with those of the coral ΔδO, which is a proxy for seawater δO and, in turn, largely controlled by local rainfall. These observations suggest that coral δC variations are closely associated with rainfall in this fregion. Given that river runoff contains dissolved inorganic carbon (DIC) with a negative δC, we suggest that periods of high rainfall on Hainan Island deliver increased amounts of C-depleted DIC to coastal seawater, resulting in an enhanced negative δC in the corals. Our findings, together with previous studies, appear to demonstrate that in coastal environments, coral skeletal δC levels are controlled mainly by terrestrial carbon input and are significantly influenced by terrestrial river runoff. Consequently, the geochemical interpretation of coral δC records may differ between coastal areas and offshore areas or the open ocean

Collective modes of a collisional anisotropic quark-gluon plasma

In this paper we consider the collective modes of a momentum-space anisotropic quark-gluon plasma taking into account the effect of collisions between the plasma constituents. Our analysis is carried out using a collisional kernel of Bhatnagar-Gross-Krook form and extends prior analyses in the literature by considering all possible angles of propagation of the gluonic modes relative to the momentum-anisotropy axis. We extract both the stable and unstable modes as a function of the collision rate and confirm prior findings that gluonic unstable modes can be eliminated from the spectrum if the collision rate is sufficiently large. In addition, we discuss the conditions necessary for the existence of unstable modes and present evidence that unstable mode growth rates are maximal for modes with momentum along the anisotropy direction. Finally, we demonstrate that when there is a finite collisional rate, gluonic unstable modes are absent from the spectrum at both small and large momentum anisotropy. These results pave the way for understanding the impact of collisions on a variety of non-equilibrium quark-gluon plasma observables.Comment: 19 pages and 15 figure