Multiple types of data are required to identify the mechanisms influencing the spatial expansion of melanoma cell colonies

Background The expansion of cell colonies is driven by a delicate balance of several mechanisms including cell motility, cell-to-cell adhesion and cell proliferation. New approaches that can be used to independently identify and quantify the role of each mechanism will help us understand how each mechanism contributes to the expansion process. Standard mathematical modelling approaches to describe such cell colony expansion typically neglect cell-to-cell adhesion, despite the fact that cell-to-cell adhesion is thought to play an important role. Results We use a combined experimental and mathematical modelling approach to determine the cell diffusivity, D, cell-to-cell adhesion strength, q, and cell proliferation rate, ?, in an expanding colony of MM127 melanoma cells. Using a circular barrier assay, we extract several types of experimental data and use a mathematical model to independently estimate D, q and ?. In our first set of experiments, we suppress cell proliferation and analyse three different types of data to estimate D and q. We find that standard types of data, such as the area enclosed by the leading edge of the expanding colony and more detailed cell density profiles throughout the expanding colony, does not provide sufficient information to uniquely identify D and q. We find that additional data relating to the degree of cell-to-cell clustering is required to provide independent estimates of q, and in turn D. In our second set of experiments, where proliferation is not suppressed, we use data describing temporal changes in cell density to determine the cell proliferation rate. In summary, we find that our experiments are best described using the range D = 161 - 243 ?m2 hour-1, q = 0.3 - 0.5 (low to moderate strength) and ? = 0.0305 - 0.0398 hour-1, and with these parameters we can accurately predict the temporal variations in the spatial extent and cell density profile throughout the expanding melanoma cell colony. Conclusions Our systematic approach to identify the cell diffusivity, cell-to-cell adhesion strength and cell proliferation rate highlights the importance of integrating multiple types of data to accurately quantify the factors influencing the spatial expansion of melanoma cell colonies.

Comparison of high level FPGA hardware design for solving tri-diagonal linear systems

Reconfigurable computing devices can increase the performance of compute intensive algorithms by implementing application specific co-processor architectures. The power cost for this performance gain is often an order of magnitude less than that of modern CPUs and GPUs. Exploiting the potential of reconfigurable devices such as Field-Programmable Gate Arrays (FPGAs) is typically a complex and tedious hardware engineering task. Re- cently the major FPGA vendors (Altera, and Xilinx) have released their own high-level design tools, which have great potential for rapid development of FPGA based custom accelerators. In this paper, we will evaluate Altera’s OpenCL Software Development Kit, and Xilinx’s Vivado High Level Sythesis tool. These tools will be compared for their per- formance, logic utilisation, and ease of development for the test case of a Tri-diagonal linear system solver.

The uber-assumption family

We offer an exposition of Boneh, Boyen, and Goh’s “uber-assumption” family for analyzing the validity and strength of pairing assumptions in the generic-group model, and augment the original BBG framework with a few simple but useful extensions.

Cryptanalysis of the LAKE hash family

We analyse the security of the cryptographic hash function LAKE-256 proposed at FSE 2008 by Aumasson, Meier and Phan. By exploiting non-injectivity of some of the building primitives of LAKE, we show three different collision and near-collision attacks on the compression function. The first attack uses differences in the chaining values and the block counter and finds collisions with complexity 233. The second attack utilizes differences in the chaining values and salt and yields collisions with complexity 242. The final attack uses differences only in the chaining values to yield near-collisions with complexity 299. All our attacks are independent of the number of rounds in the compression function. We illustrate the first two attacks by showing examples of collisions and near-collisions.

Modeling of protein signaling networks in clinical proteomics

Molecular interactions that underlie pathophysiological states are being elucidated using techniques that profile proteomicend points in cellular systems. Within the field of cancer research, protein interaction networks play pivotal roles in the establishment and maintenance of the hallmarks of malignancy, including cell division, invasion, and migration. Multiple complementary tools enable a multifaceted view of how signal protein pathway alterations contribute to pathophysiological states.One pivotal technique is signal pathway profiling of patient tissue specimens. This microanalysis technology provides a proteomic snapshot at one point in time of cells directly procured from the native context of a tumor micro environment. To study the adaptive patterns of signal pathway events over time, before and after experimental therapy, it is necessary to obtain biopsies from patients before, during, and after therapy. A complementary approach is the profiling of cultured cell lines with and without treatment. Cultured cell models provide the opportunity to study short-term signal changes occurring over minutes to hours. Through this type of system, the effects of particular pharmacological agents may be used to test the effects of signal pathway inhibition or activation on multiple endpoints within a pathway. The complexity of the data generated has necessitated the development of mathematical models for optimal interpretation of interrelated signaling pathways. In combination,clinical proteomic biopsy profiling, tissue culture proteomic profiling, and mathematical modeling synergistically enable a deeper understanding of how protein associations lead to disease states and present new insights into the design of therapeutic regimens.

A Bit-Stream based space vector modulator

Bit-Stream based control, which uses one bit wide signals to control power electronics applications, is a new approach for controller design in power electronic systems. Bit-Stream signals are inherently high frequency in nature, and as such some form of down sampling or modulating is essential to avoid excessive switching losses. This paper presents a novel three-phase space vector modulator, which is based on the Bit-Stream technique and suitable for standard three-phase inverter systems. The proposed modulator simultaneously converts a two phase reference to the three-phase domain and reduces switching frequencies to reasonable levels. The modulator consumes relatively few logic elements and does not require sector detectors, carrier oscillators or trigonometric functions. The performance of the modulator was evaluated using ModelSim. Results indicate that, subject to limits on the modulation index, the proposed modulator delivers a spread-spectrum output with total harmonic distortion comparable to standard space vector pulse width modulation techniques.

Management accounting change in a subsidiary organisation

Parent–subsidiary relationships are commonplace nowadays, yet surprisingly there is a paucity of research analysing their dynamics over time. This paper presents a (longitudinal) case study, illuminating the dynamics implicated when a UK chemicals company imposed its systems and rules on a new subsidiary. Drawing on observations from a longitudinal case study (from 1993 to 2001), the study considers: (1) the extent to which a parent imposes its (management accounting) systems,rules and procedures on a subsidiary; (2) the role which (local) political, cultural and institutional factors in a subsidiary play in shaping the dynamics of such change implementation; (3) how new systems and practices become accepted and take root as values and beliefs and how they supplement earlier norms? The study provides insight for the questions above, and draws on institutional theories and a power mobilisation framework to assist in the interpretation of observations. We find that the operations of the subsidiary company are influenced by inter-related forces, both inside and outside the organisation encompassing issues of power, politics and culture. As such, existing institutions in a subsidiary organisation are influenced, sustained, and changed by the socio-economic context in which the subsidiary is located. Organisational practices designed to secure external legitimacy are not however always symbolic and decoupled from internal operations

Melanoma cell colony expansion parameters revealed by approximate Bayesian computation

In vitro studies and mathematical models are now being widely used to study the underlying mechanisms driving the expansion of cell colonies. This can improve our understanding of cancer formation and progression. Although much progress has been made in terms of developing and analysing mathematical models, far less progress has been made in terms of understanding how to estimate model parameters using experimental in vitro image-based data. To address this issue, a new approximate Bayesian computation (ABC) algorithm is proposed to estimate key parameters governing the expansion of melanoma cell (MM127) colonies, including cell diffusivity, D, cell proliferation rate, λ, and cell-to-cell adhesion, q, in two experimental scenarios, namely with and without a chemical treatment to suppress cell proliferation. Even when little prior biological knowledge about the parameters is assumed, all parameters are precisely inferred with a small posterior coefficient of variation, approximately 2–12%. The ABC analyses reveal that the posterior distributions of D and q depend on the experimental elapsed time, whereas the posterior distribution of λ does not. The posterior mean values of D and q are in the ranges 226–268 µm2h−1, 311–351 µm2h−1 and 0.23–0.39, 0.32–0.61 for the experimental periods of 0–24 h and 24–48 h, respectively. Furthermore, we found that the posterior distribution of q also depends on the initial cell density, whereas the posterior distributions of D and λ do not. The ABC approach also enables information from the two experiments to be combined, resulting in greater precision for all estimates of D and λ.

Futile treatment in hospital: Doctors’ intergroup language

Treatment that will not provide significant net benefit at the end of a person’s life (called futile treatment) is considered by many people to represent a major problem in the health sector, as it can waste resources and raise significant ethical issues. Medical treatment at the end of life involves a complex negotiation that implicates intergroup communication between health professionals, patients, and families, as well as between groups of health professionals. This study, framed by intergroup language theory, analyzed data from a larger project on futile treatment, in order to examine the intergroup language associated with futile treatment. Hospital doctors (N = 96) were interviewed about their understanding of treatment given to adult patients at the end of life that they considered futile. We conducted a discourse analysis on doctors’ descriptions of futile treatment provided by themselves and their in-group and out-group colleagues. Results pointed to an intergroup context, with patients, families, and colleagues as out-groups. In their descriptions, doctors justified their own decisions using the language of logic, ethics, and respect. Patients and families, however, were characterized in terms of wishing and wanting, as were outgroup colleagues. In addition, out-group doctors were described in strongly negative intergroup language.

RuleOMS: A rule-based online management system

We propose an architecture for a rule-based online management systems (RuleOMS). Typically, many domain areas face the problem that stakeholders maintain databases of their business core information and they have to take decisions or create reports according to guidelines, policies or regulations. To address this issue we propose the integration of databases, in particular relational databases, with a logic reasoner and rule engine. We argue that defeasible logic is an appropriate formalism to model rules, in particular when the rules are meant to model regulations. The resulting RuleOMS provides an efficient and flexible solution to the problem at hand using defeasible inference. A case study of an online child care management system is used to illustrate the proposed architecture.

Defective co-creation: Developing a typology of consumer dysfunction in professional services

Purpose This study aims to explore the scope of consumers’ defective co-creation behaviour in professional service encounters. One of the founding premises of service-dominant logic (Vargo and Lusch, 2004, 2008) is that consumers co-create the value they derive from service encounters. In practice, however, dysfunctional consumer behaviour can obstruct value co-creation. Extant research has not yet investigated consumers’ defective co-creation behaviour in highly relational services, such as professional services, that are heavily reliant on co-creation. Design/methodology/approach To investigate defective co-creation in professional services, 164 critical incidents were collected from 38 health-care and financial service providers using the critical incident technique within semi-structured, in-depth interviews. Thematic coding was used to identify emergent themes and patterns of consumer behaviour. Findings Thematic coding resulted in a comprehensive typology of consumers’ defective co-creation behaviour that both confirms the prevalence of previously identified dysfunctional behaviours (e.g. verbal abuse and physical aggression) and identifies two new forms of consumer misbehaviour: underparticipation and overparticipation. Further, these behaviours can vary, escalate and co-occur during service encounters. Originality/value Both underparticipation and overparticipation are newly identified forms of defective co-creation that need to be examined within the broader framework of service-dominant logic (SDL).