Understanding the Dynamics of Gene Regulatory Systems : Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms

Peer reviewedPublisher PD

A Multiscale Approach for the Characterization and Crystallization of Eflucimibe Polymorphs: from Molecules to Particles

We present in this paper a generic multiscale methodology for the characterization and crystallization of eflucimibe polymorphs. The various characterization techniques used have shown that eflucimibe polymorphism is due to a conformational change of the molecule in the crystal lattice. In addition, the two polymorphs are monotropically related in the temperature range tested and have similar structures and properties (ie. interfacial tension and solubility). Consequently, it was found that for a wide range of operating conditions, the polymorphs may crystallize concomitantly. Induction time measurements and metstable zone width determination allow to infer the origin of the concomitant appearance of the polymorphs. A predominance diagram has been established which allows to perfectly control the crystallization of the desired polymorph. However, even if the stable form can be produced in a reliable way, the crystal suspension went toward a very structured gel-like network which limits the extrapolation process. Based on microscopic observation of the crystallization events performed in a microfluidic crystallizer, we propose a range of operating conditions suitable for the production of the stable form with the desired handling properties

Allele specific expression analysis identifies regulatory variation associated with stress-related genes in the Mexican highland maize landrace Palomero Toluqueño.

BackgroundGene regulatory variation has been proposed to play an important role in the adaptation of plants to environmental stress. In the central highlands of Mexico, farmer selection has generated a unique group of maize landraces adapted to the challenges of the highland niche. In this study, gene expression in Mexican highland maize and a reference maize breeding line were compared to identify evidence of regulatory variation in stress-related genes. It was hypothesised that local adaptation in Mexican highland maize would be associated with a transcriptional signature observable even under benign conditions.MethodsAllele specific expression analysis was performed using the seedling-leaf transcriptome of an F1 individual generated from the cross between the highland adapted Mexican landrace Palomero Toluqueño and the reference line B73, grown under benign conditions. Results were compared with a published dataset describing the transcriptional response of B73 seedlings to cold, heat, salt and UV treatments.ResultsA total of 2,386 genes were identified to show allele specific expression. Of these, 277 showed an expression difference between Palomero Toluqueño and B73 alleles under benign conditions that anticipated the response of B73 cold, heat, salt and/or UV treatments, and, as such, were considered to display a prior stress response. Prior stress response candidates included genes associated with plant hormone signaling and a number of transcription factors. Construction of a gene co-expression network revealed further signaling and stress-related genes to be among the potential targets of the transcription factors candidates.DiscussionPrior activation of responses may represent the best strategy when stresses are severe but predictable. Expression differences observed here between Palomero Toluqueño and B73 alleles indicate the presence of cis-acting regulatory variation linked to stress-related genes in Palomero Toluqueño. Considered alongside gene annotation and population data, allele specific expression analysis of plants grown under benign conditions provides an attractive strategy to identify functional variation potentially linked to local adaptation

A mathematical approach towards hardware design

Today the hardware for embedded systems is often specified in VHDL. However, VHDL describes the system at a rather low level, which is cumbersome and may lead to design faults in large real life applications. There is a need of higher level abstraction mechanisms. In the embedded systems group of the University of Twente we are working on systematic and transformational methods to design hardware architectures, both multi core and single core. The main line in this approach is to start with a straightforward (often mathematical) specification of the problem. The next step is to find some adequate transformations on this specification, in particular to find specific optimizations, to be able to distribute the application over different cores. The result of these transformations is then translated into the functional programming language Haskell since Haskell is close to mathematics and such a translation often is straightforward. Besides, the Haskell code is executable, so one immediately has a simulation of the intended system. Next, the resulting Haskell specification is given to a compiler, called CëaSH (for CAES LAnguage for Synchronous Hardware) which translates the specification into VHDL. The resulting VHDL is synthesizable, so from there on standard VHDL-tooling can be used for synthesis. In this work we primarily focus on streaming applications: i.e. applications that can be modeled as data-flow graphs. At the moment the CëaSH system is ready in prototype form and in the presentation we will give several examples of how it can be used. In these examples it will be shown that the specification code is clear and concise. Furthermore, it is possible to use powerful abstraction mechanisms, such as polymorphism, higher order functions, pattern matching, lambda abstraction, partial application. These features allow a designer to describe circuits in a more natural and concise way than possible with the language elements found in the traditional hardware description languages. In addition we will give some examples of transformations that are possible in a mathematical specification, and which do not suffer from the problems encountered in, e.g., automatic parallelization of nested for-loops in C-programs

Polymorphic computing abstraction for heterogeneous architectures

Integration of multiple computing paradigms onto system on chip (SoC) has pushed the boundaries of design space exploration for hardware architectures and computing system software stack. The heterogeneity of computing styles in SoC has created a new class of architectures referred to as Heterogeneous Architectures. Novel applications developed to exploit the different computing styles are user centric for embedded SoC. Software and hardware designers are faced with several challenges to harness the full potential of heterogeneous architectures. Applications have to execute on more than one compute style to increase overall SoC resource utilization. The implication of such an abstraction is that application threads need to be polymorphic. Operating system layer is thus faced with the problem of scheduling polymorphic threads. Resource allocation is also an important problem to be dealt by the OS. Morphism evolution of application threads is constrained by the availability of heterogeneous computing resources. Traditional design optimization goals such as computational power and lower energy per computation are inadequate to satisfy user centric application resource needs. Resource allocation decisions at application layer need to permeate to the architectural layer to avoid conflicting demands which may affect energy-delay characteristics of application threads. We propose Polymorphic computing abstraction as a unified computing model for heterogeneous architectures to address the above issues. Simulation environment for polymorphic applications is developed and evaluated under various scheduling strategies to determine the effectiveness of polymorphism abstraction on resource allocation. User satisfaction model is also developed to complement polymorphism and used for optimization of resource utilization at application and network layer of embedded systems