The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction

Purpose: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. Methods: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. Results: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55α subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55α but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. Conclusion: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported

Eijndhoven. Compositional memory systems for data intensive applications

Conventional cache models are not suited for real-time parallel processing because tasks may flush each other’s data out of the cache in an unpredictable manner. In this way the system is not compositional so the overall performance is difficult to predict and the integration of new tasks expensive. This paper proposes a new method that imposes compositionality to the system’s performance and makes different memory hierarchy optimizations possible for multimedia communicating tasks when running on embedded multiprocessor architectures. The method is based on a cache allocation strategy that assigns sets of the unified cache exclusively to tasks and to the communication buffers. We also analytically formulate the problem and describe a method to compute the cache partitioning ratio for optimizing the throughput and the consumed power. When applied to a multiprocessor with memory hierarchy our technique delivers also performance gain. Compared to the shared cache case, for an application consisting of two jpeg decoders and one edge detection algorithm 5 times less misses are experienced and for an mpeg2 decoder 6.5 times less misses are experienced. 1

High-Level Synthesis Scheduling and Allocation using Genetic Algorithms based on Constructive Topological Scheduling Techniques

In this article constructive scheduling methods combined with genetic algorithms are used to searchfor a suitable order to schedule the operations. The method is extended with an encoding capable of allocating supplementary resources during scheduling. This makes it very suitable in high-level synthesis strategies based on lower bound estimations techniques. Experiments and comparisons show high quality results and fast run times that outperform results produced by other heuristic scheduling methods 1 Introduction During high-level synthesis a behavioral description of a chip is translated into a digital network structure [McFa90]. The behavioral description consists of calculations (like additions, multiplications, logical operations etc.) and control structures (like conditionals, loops and procedure calls) which are used to transform input data into output data. The digital network structure consists of functional modules (adders, multipliers, ALUs, logical gates), storage (like r..

High-Level Synthesis Scheduling and Allocation using Genetic Algorithms

In this article a scheduling method is presented which is capable of allocating supplementary resources during scheduling. This makes it very suitable in synthesis strategies based on lower bound estimations techniques. The method is based on genetic algorithms. Special coding techniques and analysis methods are used to improve the runtime and quality of the results. The scheduler can easily be extended to coverother architectural issues and (for example) providesways to make trade-offs between functional unit allocation and register allocation. Experiments and comparisons show high quality results and fast run times that outperform results produced by other heuristic scheduling methods 1 Introduction High-level synthesis translates behavioral descriptions into digital network structures. During this translation the cycle steps in which operations start their execution must be determined (scheduling problem). A schedule induces a resource allocation (because some operations are execut..

Cache Partitioning Options for Compositional Multimedia Applications

The use of conventional probabilistic cache models in embedded multimedia systems is restricted because the tasks flush each others data out of the cache in an unpredictable manner making the system not compositional. In this way the overall performance is difficult to predict and the integration of new tasks expensive. In a multiprocessor platform the unified levels of cache shared between processors are causing the largest task conflicts. Our proposal is to introduce a compositionality property to the system such that the overall performance can be easily computed if the components’ performance in known. This property is obtained by means of assigning each task their exclusive part of the unified level of cache shared between processors. This article also presents the results of the effect on performance (measured in number of cache misses) of two types of cache partitioning, namely set based and associativity based partitioning, for the case of multimedia applications. Our experiments indicate that when applied to a multiprocessor with memory hierarchy the set based partitioning performs always better that the associativity based partitioning. Moreover set based partitioning typically results in performance gain of up to 35 % less misses, where the associativity based partitioning always results in large performance degradation of 17 % to 150 % more misses, when compared with the shared cache case. I

Gradients in the composition of enamel and dentin mineral in rat incisors

In order to investigate possible diffrences in the mineral composition of rat incisors, Wistar rats received either a zinc-deficient or a normal diet (the latter were pair fed or ad libitum). Three incisors from each group were subjected to microanalysis by me electron microprobe. No differences were found in mineraI composition between the three groups. The average molar Ca/P ratio in the enamel and the dentin were (1.62+/- 0.05) and ( 1.50 +/- 0.05), respectively. The distribution of sodium and magnesium over the dentin was homogeneous and inhomogeneous , respectively. Dentin did not contain detectable amounts of chlorine. The gradients for sodium, magnesium and chlorine as a function of depth in enamel were similar to those reported for these elements in human and rhesus monkey enamel : sodium and magnesium had a low concentration at the enamel surface, wnereas chlorine had a high concentration there