Regulation of histone H2A.Z expression is mediated by sirtuin 1 in prostate cancer

Histone variants seem to play a major role in gene expression regulation. In prostate cancer, H2A.Z and its acetylated form are implicated in oncogenes’ upregulation. SIRT1, which may act either as tumor suppressor or oncogene, reduces H2A.Z levels in cardiomyocytes, via proteasome-mediated degradation, and this mechanism might be impaired in prostate cancer cells due to sirtuin 1 downregulation. Thus, we aimed to characterize the mechanisms underlying H2A.Z and SIRT1 deregulation in prostate carcinogenesis and how they interact. We found that H2AFZ and SIRT1 were up- and downregulated, respectively, at transcript level in primary prostate cancer and high-grade prostatic intraepithelial neoplasia compared to normal prostatic tissues. Induced SIRT1 overexpression in prostate cancer cell lines resulted in almost complete absence of H2A.Z. Inhibition of mTOR had a modest effect on H2A.Z levels, but proteasome inhibition prevented the marked reduction of H2A.Z due to sirtuin 1 overexpression. Prostate cancer cells exposed to epigenetic modifying drugs trichostatin A, alone or combined with 5-aza-2’-deoxycytidine, increased H2AFZ transcript, although with a concomitant decrease in protein levels. Conversely, SIRT1 transcript and protein levels increased after exposure. ChIP revealed an increase of activation marks within the TSS region for both genes. Remarkably, inhibition of sirtuin 1 with nicotinamide, increased H2A.Z levels, whereas activation of sirtuin 1 by resveratrol led to an abrupt decrease in H2A.Z. Finally, protein-ligation assay showed that exposure to epigenetic modifying drugs fostered the interaction between sirtuin 1 and H2A.Z. We concluded that sirtuin 1 and H2A.Z deregulation in prostate cancer are reciprocally related. Epigenetic mechanisms, mostly histone post-translational modifications, are likely involved and impair sirtuin 1-mediated downregulation of H2A.Z via proteasome-mediated degradation. Epigenetic modifying drugs in conjunction with enzymatic modulators are able to restore the normal functions of sirtuin 1 and might constitute relevant tools for targeted therapy of prostate cancer patients

Many-core approach to 2D-DCT calculation using an FPGA

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia de Electrónica e Telecomunicações

Application mapping in NoC-Based many-cores

Many-core platforms based on Network-on-Chip (NoC [Benini and De Micheli 2002]) present an emerging technology in the real-time embedded domain. Although the idea to group the applications previously executed on separated single-core devices, and accommodate them on an individual many-core chip offers various options for power savings, cost reductions and contributes to the overall system flexibility, its implementation is a non-trivial task. In this paper we address the issue of application mapping onto a NoCbased many-core platform when considering fundamentals and trends of current many-core operating systems, specifically, we elaborate on a limited migrative application model encompassing a message-passing paradigm as a communication primitive. As the main contribution, we formulate the problem of real-time application mapping, and propose a three-stage process to efficiently solve it. Through analysis it is assured that derived solutions guarantee the fulfilment of posed time constraints regarding worst-case communication latencies, and at the same time provide an environment to perform load balancing for e.g. thermal, energy, fault tolerance or performance reasons.We also propose several constraints regarding the topological structure of the application mapping, as well as the inter- and intra-application communication patterns, which efficiently solve the issues of pessimism and/or intractability when performing the analysis.

Preemption-light multiprocessor scheduling of sporadic tasks with high utilisation bound

Known algorithms capable of scheduling implicit-deadline sporadic tasks over identical processors at up to 100% utilisation invariably involve numerous preemptions and migrations. To the challenge of devising a scheduling scheme with as few preemptions and migrations as possible, for a given guaranteed utilisation bound, we respond with the algorithm NPS-F. It is configurable with a parameter, trading off guaranteed schedulable utilisation (up to 100%) vs preemptions. For any possible configuration, NPS-F introduces fewer preemptions than any other known algorithm matching its utilisation bound. A clustered variant of the algorithm, for systems made of multicore chips, eliminates (costly) off-chip task migrations, by dividing processors into disjoint clusters, formed by cores on the same chip (with the cluster size being a parameter). Clusters are independently scheduled (each, using non-clustered NPS-F). The utilisation bound is only moderately affected. We also formulate an important extension (applicable to both clustered and non-clustered NPS-F) which optimises the supply of processing time to executing tasks and makes it more granular. This reduces processing capacity requirements for schedulability without increasing preemptions.

Software transactional memory as a building block for parallel embedded realtime systems

The recent trends of chip architectures with higher number of heterogeneous cores, and non-uniform memory/non-coherent caches, brings renewed attention to the use of Software Transactional Memory (STM) as a fundamental building block for developing parallel applications. Nevertheless, although STM promises to ease concurrent and parallel software development, it relies on the possibility of aborting conflicting transactions to maintain data consistency, which impacts on the responsiveness and timing guarantees required by embedded real-time systems. In these systems, contention delays must be (efficiently) limited so that the response times of tasks executing transactions are upper-bounded and task sets can be feasibly scheduled. In this paper we assess the use of STM in the development of embedded real-time software, defending that the amount of contention can be reduced if read-only transactions access recent consistent data snapshots, progressing in a wait-free manner. We show how the required number of versions of a shared object can be calculated for a set of tasks. We also outline an algorithm to manage conflicts between update transactions that prevents starvation.

A parallel programming model for ada

Over the last three decades, computer architects have been able to achieve an increase in performance for single processors by, e.g., increasing clock speed, introducing cache memories and using instruction level parallelism. However, because of power consumption and heat dissipation constraints, this trend is going to cease. In recent times, hardware engineers have instead moved to new chip architectures with multiple processor cores on a single chip. With multi-core processors, applications can complete more total work than with one core alone. To take advantage of multi-core processors, parallel programming models are proposed as promising solutions for more effectively using multi-core processors. This paper discusses some of the existent models and frameworks for parallel programming, leading to outline a draft parallel programming model for Ada.

Estudo sobre a memória longa na volatilidade dos preços do ouro : uma abordagem com base nos modelos de tipo ARCH

Mestrado em Contabilidade e Análise Financeira

Global-EDF scheduling of multimode real- time systems considering mode independent tasks

Embedded real-time systems often have to support the embedding system in very different and changing application scenarios. An aircraft taxiing, taking off and in cruise flight is one example. The different application scenarios are reflected in the software structure with a changing task set and thus different operational modes. At the same time there is a strong push for integrating previously isolated functionalities in single-chip multicore processors. On such multicores the behavior of the system during a mode change, when the systems transitions from one mode to another, is complex but crucial to get right. In the past we have investigated mode change in multiprocessor systems where a mode change requires a complete change of task set. Now, we present the first analysis which considers mode changes in multicore systems, which use global EDF to schedule a set of mode independent (MI) and mode specific (MS) tasks. In such systems, only the set of MS tasks has to be replaced during mode changes, without jeopardizing the schedulability of the MI tasks. Of prime concern is that the mode change is safe and efficient: i.e. the mode change needs to be performed in a predefined time window and no deadlines may be missed as a function of the mode change.

A tighter analysis of the worst-case endto- end communication delay in massive multicores

"Many-core” systems based on the Network-on- Chip (NoC) architecture have brought into the fore-front various opportunities and challenges for the deployment of real-time systems. Such real-time systems need timing guarantees to be fulfilled. Therefore, calculating upper-bounds on the end-to-end communication delay between system components is of primary interest. In this work, we identify the limitations of an existing approach proposed by [1] and propose different techniques to overcome these limitations.

Managing contention of software transactional memory in real-time systems

The foreseen evolution of chip architectures to higher number of, heterogeneous, cores, with non-uniform memory and non-coherent caches, brings renewed attention to the use of Software Transactional Memory (STM) as an alternative to lock-based synchronisation. However, STM relies on the possibility of aborting conflicting transactions to maintain data consistency, which impacts on the responsiveness and timing guarantees required by real-time systems. In these systems, contention delays must be (efficiently) limited so that the response times of tasks executing transactions are upperbounded and task sets can be feasibly scheduled. In this paper we defend the role of the transaction contention manager to reduce the number of transaction retries and to help the real-time scheduler assuring schedulability. For such purpose, the contention management policy should be aware of on-line scheduling information.

An embedded 1149.4 extension to support mixed-signal debugging

Debugging electronic circuits is traditionally done with bench equipment directly connected to the circuit under debug. In the digital domain, the difficulties associated with the direct physical access to circuit nodes led to the inclusion of resources providing support to that activity, first at the printed circuit level, and then at the integrated circuit level. The experience acquired with those solutions led to the emergence of dedicated infrastructures for debugging cores at the system-on-chip level. However, all these developments had a small impact in the analog and mixed-signal domain, where debugging still depends, to a large extent, on direct physical access to circuit nodes. As a consequence, when analog and mixed-signal circuits are integrated as cores inside a system-on-chip, the difficulties associated with debugging increase, which cause the time-to-market and the prototype verification costs to also increase. The present work considers the IEEE1149.4 infrastructure as a means to support the debugging of mixed-signal circuits, namely to access the circuit nodes and also an embedded debug mechanism named mixed-signal condition detector, necessary for watch-/breakpoints and real-time analysis operations. One of the main advantages associated with the proposed solution is the seamless migration to the system-on-chip level, as the access is done through electronic means, thus easing debugging operations at different hierarchical levels.

Real time fault injection using a modified debugging infrastructure

Dependability is a critical factor in computer systems, requiring high quality validation & verification procedures in the development stage. At the same time, digital devices are getting smaller and access to their internal signals and registers is increasingly complex, requiring innovative debugging methodologies. To address this issue, most recent microprocessors include an on-chip debug (OCD) infrastructure to facilitate common debugging operations. This paper proposes an enhanced OCD infrastructure with the objective of supporting the verification of fault-tolerant mechanisms through fault injection campaigns. This upgraded on-chip debug and fault injection (OCD-FI) infrastructure provides an efficient fault injection mechanism with improved capabilities and dynamic behavior. Preliminary results show that this solution provides flexibility in terms of fault triggering and allows high speed real-time fault injection in memory elements

Real time fault injection using enhanced OCD -- a performance analysis

Fault injection is frequently used for the verification and validation of dependable systems. When targeting real time microprocessor based systems the process becomes significantly more complex. This paper proposes two complementary solutions to improve real time fault injection campaign execution, both in terms of performance and capabilities. The methodology is based on the use of the on-chip debug mechanisms present in modern electronic devices. The main objective is the injection of faults in microprocessor memory elements with minimum delay and intrusiveness. Different configurations were implemented and compared in terms of performance gain and logic overhead.

Using NEXUS compliant debuggers for real time fault injection on microprocessors

As electronic devices get smaller and more complex, dependability assurance is becoming fundamental for many mission critical computer based systems. This paper presents a case study on the possibility of using the on-chip debug infrastructures present in most current microprocessors to execute real time fault injection campaigns. The proposed methodology is based on a debugger customized for fault injection and designed for maximum flexibility, and consists of injecting bit-flip type faults on memory elements without modifying or halting the target application. The debugger design is easily portable and applicable to different architectures, providing a flexible and efficient mechanism for verifying and validating fault tolerant components.

Compact, frequency reconfigurable, printed monopole antenna

This paper proposes a possible implementation of a compact printed monopole antenna, useful to operate in UMTS and WLAN bands. In order to accomplish that, a miniaturization technique based on the application of chip inductors is used in conjunction with frequency reconfiguration capability. The chip inductors change the impedance response of the monopole, allowing to reduce the resonant frequency. In order to be able to operate the antenna in these two different frequencies, an antenna reconfiguration technique based on PIN diodes is applied. This procedure allows the change of the active form of the antenna leading to a shift in the resonant frequency. The prototype measurements show good agreement with the simulation results.