STL-based Analysis of TRAIL-induced Apoptosis Challenges the Notion of Type I/Type II Cell Line Classification

Extrinsic apoptosis is a programmed cell death triggered by external ligands, such as the TNF-related apoptosis inducing ligand (TRAIL). Depending on the cell line, the specific molecular mechanisms leading to cell death may significantly differ. Precise characterization of these differences is crucial for understanding and exploiting extrinsic apoptosis. Cells show distinct behaviors on several aspects of apoptosis, including (i) the relative order of caspases activation, (ii) the necessity of mitochondria outer membrane permeabilization (MOMP) for effector caspase activation, and (iii) the survival of cell lines overexpressing Bcl2. These differences are attributed to the activation of one of two pathways, leading to classification of cell lines into two groups: type I and type II. In this work we challenge this type I/type II cell line classification. We encode the three aforementioned distinguishing behaviors in a formal language, called signal temporal logic (STL), and use it to extensively test the validity of a previously-proposed model of TRAIL-induced apoptosis with respect to experimental observations made on different cell lines. After having solved a few inconsistencies using STL-guided parameter search, we show that these three criteria do not define consistent cell line classifications in type I or type II, and suggest mutants that are predicted to exhibit ambivalent behaviors. In particular, this finding sheds light on the role of a feedback loop between caspases, and reconciliates two apparently-conflicting views regarding the importance of either upstream or downstream processes for cell-type determination. More generally, our work suggests that these three distinguishing behaviors should be merely considered as type I/II features rather than cell-type defining criteria. On the methodological side, this work illustrates the biological relevance of STL-diagrams, STL population data, and STL-guided parameter search implemented in the tool Breach. Such tools are well-adapted to the ever-increasing availability of heterogeneous knowledge on complex signal transduction pathways

Thin-film flow in helically wound rectangular channels with small torsion

Laminar gravity-driven thin-film flow down a helically-wound channel of rectangular cross-section with small torsion in which the fluid depth is small is considered. Neglecting the entrance and exit regions we obtain the steady-state solution that is independent of position along the axis of the channel, so that the flow, which comprises a primary flow in the direction of the axis of the channel and a secondary flow in the cross-sectional plane, depends only on position in the two-dimensional cross-section of the channel. A thin-film approximation yields explicit expressions for the fluid velocity and pressure in terms of the free-surface shape, the latter satisfying a non-linear ordinary differential equation that has a simple exact solution in the special case of a channel of rectangular cross-section. The predictions of the thin-film model are shown to be in good agreement with much more computationally intensive solutions of the small-helix-torsion Navier–Stokes equations. The present work has particular relevance to spiral particle separators used in the mineral-processing industry. The validity of an assumption commonly used in modelling flow in spiral separators, namely that the flow in the outer region of the separator cross-section is described by a free vortex, is shown to depend on the problem parameters

Socio-economic impact of cluster marketing: The case of Ned Landcare Association sweet pepper cluster

Through clustering, opportunities exist for smallholder farmers to organize their output and to sell directly to institutional markets. This paper analyses the experiences of the cluster marketing approach in Barangay Ned, Lake Sebu, South Cotabato. The case demonstrates how farmers in the cluster group developed an enterprise plan, established linkages with a microfinance institution and negotiated sales to downstream market intermediaries. Farmers in the cluster increased their technical and marketing knowledge, improved their farming and marketing practices, improved their access to capital and increased their income. Trust, confidence, commitment and unity among cluster members were established through the cluster marketing approach

Uniqueness of the compactly supported weak solutions of the relativistic Vlasov-Darwin system

We use optimal transportation techniques to show uniqueness of the compactly supported weak solutions of the relativistic Vlasov-Darwin system. Our proof extends the method used by Loeper in J. Math. Pures Appl. 86, 68-79 (2006) to obtain uniqueness results for the Vlasov-Poisson system.Comment: AMS-LaTeX, 21 page

A general computational method for robustness analysis with applications to synthetic gene networks

Motivation: Robustness is the capacity of a system to maintain a function in the face of perturbations. It is essential for the correct functioning of natural and engineered biological systems. Robustness is generally defined in an ad hoc, problem-dependent manner, thus hampering the fruitful development of a theory of biological robustness, recently advocated by Kitano

Reachability in Biochemical Dynamical Systems by Quantitative Discrete Approximation (extended abstract)

In this paper, a novel computational technique for finite discrete approximation of continuous dynamical systems suitable for a significant class of biochemical dynamical systems is introduced. The method is parameterized in order to affect the imposed level of approximation provided that with increasing parameter value the approximation converges to the original continuous system. By employing this approximation technique, we present algorithms solving the reachability problem for biochemical dynamical systems. The presented method and algorithms are evaluated on several exemplary biological models and on a real case study.Comment: In Proceedings CompMod 2011, arXiv:1109.104

Thin-film flow in helically wound shallow channels of arbitrary cross-sectional shape

We consider the steady, gravity-driven flow of a thin film of viscous fluid down a helically wound shallow channel of arbitrary cross-sectional shape with arbitrary torsion and curvature. This extends our previous work [D. J. Arnold et al., “Thin-film flow in helically-wound rectangular channels of arbitrary torsion and curvature,” J. Fluid Mech. 764, 76–94 (2015)] on channels of rectangular cross section. The Navier-Stokes equations are expressed in a novel, non-orthogonal coordinate system fitted to the channel bottom. By assuming that the channel depth is small compared to its width and that the fluid depth in the vertical direction is also small compared to its typical horizontal extent, we are able to solve for the velocity components and pressure analytically. Using these results, a differential equation for the free surface shape is obtained, which must in general be solved numerically. Motivated by the aim of understanding flows in static spiral particle separators used in mineral processing, we investigate the effect of cross-sectional shape on the secondary flow in the channel cross section. We show that the competition between gravity and inertia in non-rectangular channels is qualitatively similar to that in rectangular channels, but that the cross-sectional shape has a strong influence on the breakup of the secondary flow into multiple clockwise-rotating cells. This may be triggered by small changes to the channel geometry, such as one or more bumps in the channel bottom that are small relative to the fluid depth. In contrast to the secondary flow which is quite sensitive to small bumps in the channel bottom, the free-surface profile is relatively insensitive to these. The sensitivity of the flow to the channel geometry may have important implications for the design of efficient spiral particle separators.D. J. Arnold, Y. M. Stokes, and J. E. F. Gree

Partnership, ownership and control: the impact of corporate governance on employment relations

Prevailing patterns of dispersed share ownership and rules of corporate governance for UK listed companies appear to constrain the ability of managers to make credible, long-term commitments to employees of the kind needed to foster effective labour-management partnerships. We present case study evidence which suggests that such partnerships can nevertheless emerge where product market conditions and the regulatory environment favour a stakeholder orientation. Proactive and mature partnerships may also be sustained where the board takes a strategic approach to mediating between the claims of different stakeholder groups, institutional investors are prepared to take a long-term view of their holdings, and strong and independent trade unions are in a position to facilitate organisational change

Investigation of the nonlocal coherent-potential approximation

Recently the nonlocal coherent-potential approximation (NLCPA) has been introduced by Jarrell and Krishnamurthy for describing the electronic structure of substitutionally disordered systems. The NLCPA provides systematic corrections to the widely used coherent-potential approximation (CPA) whilst preserving the full symmetry of the underlying lattice. Here an analytical and systematic numerical study of the NLCPA is presented for a one-dimensional tight-binding model Hamiltonian, and comparisons with the embedded cluster method (ECM) and molecular coherent potential approximation (MCPA) are made.Comment: 18 pages, 5 figure

Contested resources: unions, employers, and the adoption of new work practices in US and UK telecommunications

The pattern of adoption of high-performance work practices has been explained in terms of strategic contingency and in terms of union presence. We compare the post-deregulation/privatization changes in work practice at AT&T, Bell Atlantic and British Telecom. On the basis of these cases, we argue that the choice of new work practices should be understood as a consequence not only of the company's resources or changes in its environment, nor of a simple union presence, but also as a consequence of the practices' effects on union power, the nature of the union's engagement, and the union's strategic choices