Run-time management for future MPSoC platforms

In recent years, we are witnessing the dawning of the Multi-Processor Systemon- Chip (MPSoC) era. In essence, this era is triggered by the need to handle more complex applications, while reducing overall cost of embedded (handheld) devices. This cost will mainly be determined by the cost of the hardware platform and the cost of designing applications for that platform. The cost of a hardware platform will partly depend on its production volume. In turn, this means that ??exible, (easily) programmable multi-purpose platforms will exhibit a lower cost. A multi-purpose platform not only requires ??exibility, but should also combine a high performance with a low power consumption. To this end, MPSoC devices integrate computer architectural properties of various computing domains. Just like large-scale parallel and distributed systems, they contain multiple heterogeneous processing elements interconnected by a scalable, network-like structure. This helps in achieving scalable high performance. As in most mobile or portable embedded systems, there is a need for low-power operation and real-time behavior. The cost of designing applications is equally important. Indeed, the actual value of future MPSoC devices is not contained within the embedded multiprocessor IC, but in their capability to provide the user of the device with an amount of services or experiences. So from an application viewpoint, MPSoCs are designed to ef??ciently process multimedia content in applications like video players, video conferencing, 3D gaming, augmented reality, etc. Such applications typically require a lot of processing power and a signi??cant amount of memory. To keep up with ever evolving user needs and with new application standards appearing at a fast pace, MPSoC platforms need to be be easily programmable. Application scalability, i.e. the ability to use just enough platform resources according to the user requirements and with respect to the device capabilities is also an important factor. Hence scalability, ??exibility, real-time behavior, a high performance, a low power consumption and, ??nally, programmability are key components in realizing the success of MPSoC platforms. The run-time manager is logically located between the application layer en the platform layer. It has a crucial role in realizing these MPSoC requirements. As it abstracts the platform hardware, it improves platform programmability. By deciding on resource assignment at run-time and based on the performance requirements of the user, the needs of the application and the capabilities of the platform, it contributes to ??exibility, scalability and to low power operation. As it has an arbiter function between different applications, it enables real-time behavior. This thesis details the key components of such an MPSoC run-time manager and provides a proof-of-concept implementation. These key components include application quality management algorithms linked to MPSoC resource management mechanisms and policies, adapted to the provided MPSoC platform services. First, we describe the role, the responsibilities and the boundary conditions of an MPSoC run-time manager in a generic way. This includes a de??nition of the multiprocessor run-time management design space, a description of the run-time manager design trade-offs and a brief discussion on how these trade-offs affect the key MPSoC requirements. This design space de??nition and the trade-offs are illustrated based on ongoing research and on existing commercial and academic multiprocessor run-time management solutions. Consequently, we introduce a fast and ef??cient resource allocation heuristic that considers FPGA fabric properties such as fragmentation. In addition, this thesis introduces a novel task assignment algorithm for handling soft IP cores denoted as hierarchical con??guration. Hierarchical con??guration managed by the run-time manager enables easier application design and increases the run-time spatial mapping freedom. In turn, this improves the performance of the resource assignment algorithm. Furthermore, we introduce run-time task migration components. We detail a new run-time task migration policy closely coupled to the run-time resource assignment algorithm. In addition to detailing a design-environment supported mechanism that enables moving tasks between an ISP and ??ne-grained recon??gurable hardware, we also propose two novel task migration mechanisms tailored to the Network-on-Chip environment. Finally, we propose a novel mechanism for task migration initiation, based on reusing debug registers in modern embedded microprocessors. We propose a reactive on-chip communication management mechanism. We show that by exploiting an injection rate control mechanism it is possible to provide a communication management system capable of providing a soft (reactive) QoS in a NoC. We introduce a novel, platform independent run-time algorithm to perform quality management, i.e. to select an application quality operating point at run-time based on the user requirements and the available platform resources, as reported by the resource manager. This contribution also proposes a novel way to manage the interaction between the quality manager and the resource manager. In order to have a the realistic, reproducible and ??exible run-time manager testbench with respect to applications with multiple quality levels and implementation tradev offs, we have created an input data generation tool denoted Pareto Surfaces For Free (PSFF). The the PSFF tool is, to the best of our knowledge, the ??rst tool that generates multiple realistic application operating points either based on pro??ling information of a real-life application or based on a designer-controlled random generator. Finally, we provide a proof-of-concept demonstrator that combines these concepts and shows how these mechanisms and policies can operate for real-life situations. In addition, we show that the proposed solutions can be integrated into existing platform operating systems

Birationality of \'etale morphisms via surgery

We use a counting argument and surgery theory to show that if $D$ is a sufficiently general algebraic hypersurface in $\Bbb C^n$, then any local diffeomorphism $F:X \to \Bbb C^n$ of simply connected manifolds which is a $d$-sheeted cover away from $D$ has degree $d=1$ or $d=\infty$ (however all degrees $d > 1$ are possible if $F$ fails to be a local diffeomorphism at even a single point). In particular, any \'etale morphism $F:X \to \Bbb C^n$ of algebraic varieties which covers away from such a hypersurface $D$ must be birational.Comment: 17 pages. Replaced to add further references and make language more consistent with the literatur

Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine clinical model of spinal cord injury

Many hundreds of thousands of people around the world are living with the long-term consequences of spinal cord injury and they need effective new therapies. Laboratory research in experimental animals has identified a large number of potentially translatable interventions but transition to the clinic is not straightforward. Further evidence of efficacy in more clinically-relevant lesions is required to gain sufficient confidence to commence human clinical trials. Of the many therapeutic candidates currently available, intraspinally applied chondroitinase ABC has particularly well documented efficacy in experimental animals. In this study we measured the effects of this intervention in a double-blinded randomized controlled trial in a cohort of dogs with naturally-occurring severe chronic spinal cord injuries that model the condition in humans. First, we collected baseline data on a series of outcomes: forelimb-hindlimb coordination (the prespecified primary outcome measure), skin sensitivity along the back, somatosensory evoked and transcranial magnetic motor evoked potentials and cystometry in 60 dogs with thoracolumbar lesions. Dogs were then randomized 1:1 to receive intraspinal injections of heat-stabilized, lipid microtube-embedded chondroitinase ABC or sham injections consisting of needle puncture of the skin. Outcome data were measured at 1, 3 and 6 months after intervention; skin sensitivity was also measured 24 h after injection (or sham). Forelimb-hindlimb coordination was affected by neither time nor chondroitinase treatment alone but there was a significant interaction between these variables such that coordination between forelimb and hindlimb stepping improved during the 6-month follow-up period in the chondroitinase-treated animals by a mean of 23%, but did not change in controls. Three dogs (10%) in the chondroitinase group also recovered the ability to ambulate without assistance. Sensitivity of the dorsal skin increased at 24 h after intervention in both groups but subsequently decreased to normal levels. Cystometry identified a non-significant improvement of bladder compliance at 1 month in the chondroitinase-injected dogs but this did not persist. There were no overall differences between groups in detection of sensory evoked potentials. Our results strongly support a beneficial effect of intraspinal injection of chondroitinase ABC on spinal cord function in this highly clinically-relevant model of chronic severe spinal cord injury. There was no evidence of long-term adverse effects associated with this intervention. We therefore conclude that this study provides strong evidence in support of initiation of clinical trials of chondroitinase ABC in humans with chronic spinal cord injury

The fundamental constants and their variation: observational status and theoretical motivations

This article describes the various experimental bounds on the variation of the fundamental constants of nature. After a discussion on the role of fundamental constants, of their definition and link with metrology, the various constraints on the variation of the fine structure constant, the gravitational, weak and strong interactions couplings and the electron to proton mass ratio are reviewed. This review aims (1) to provide the basics of each measurement, (2) to show as clearly as possible why it constrains a given constant and (3) to point out the underlying hypotheses. Such an investigation is of importance to compare the different results, particularly in view of understanding the recent claims of the detections of a variation of the fine structure constant and of the electron to proton mass ratio in quasar absorption spectra. The theoretical models leading to the prediction of such variation are also reviewed, including Kaluza-Klein theories, string theories and other alternative theories and cosmological implications of these results are discussed. The links with the tests of general relativity are emphasized.Comment: 56 pages, l7 figures, submitted to Rev. Mod. Phy

MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase–PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC

Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone

Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass

MUC4 mucin expression in human pancreatic tumours is affected by organ environment: the possible role of TGFβ2

MUC4 is highly expressed in human pancreatic tumours and pancreatic tumour cell lines, but is minimally or not expressed in normal pancreas or chronic pancreatitis. Here, we investigated the aberrant regulation of MUC4 expression in vivo using clonal human pancreatic tumour cells (CD18/HPAF) grown either orthotopically in the pancreas (OT) or ectopically in subcutaneous tissue (SC) in the nude mice. Histological examination of the OT and SC tumours showed moderately differentiated and anaplastic morphology, respectively. The OT tumour cells showed metastases to distant lymph nodes and faster tumour growth (

The nucleus reuniens: a key node in the neurocircuitry of stress and depression

Uncorrected proofThe hippocampus and prefrontal cortex (PFC) are connected in a reciprocal manner: whereas the hippocampus projects directly to the PFC, a polysynaptic pathway that passes through the nucleus reuniens (RE) of the thalamus relays inputs from the PFC to the hippocampus. The present study demonstrates that lesioning and/or inactivation of the RE reduces coherence in the PFC-hippocampal pathway, provokes an antidepressant-like behavioral response in the forced swim test and prevents, but does not ameliorate, anhedonia in the chronic mild stress (CMS) model of depression. Additionally, RE lesioning before CMS abrogates the well-known neuromorphological and endocrine correlates of CMS. In summary, this work highlights the importance of the reciprocal connectivity between the hippocampus and PFC in the establishment of stress-induced brain pathology and suggests a role for the RE in promoting resilience to depressive illness.Greece for providing sertraline. This work was supported by an ‘Education and Lifelong Learning, Supporting Postdoctoral Researchers’, co-financed by the European Social Fund (ESF) and the General Secretariat for Research and Technology, Greece, the Life and Health Sciences Research Institute (ICVS), ON.2—O NOVO NORTE—North Portugal Regional Operational Program 2007/2013 of the National Strategic Reference Framework (NSRF) 2007/2013 through the European Regional Development Fund (ERDF), the Portuguese Foundation for Science and Technology (FCT; grant no. NMC-113934) and an InEurope program funded by International Brain Research Organizationinfo:eu-repo/semantics/publishedVersio

A comparative study between mixed-type tumours from human salivary and canine mammary glands

<p>Abstract</p> <p>Background</p> <p>In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours.</p> <p>Methods</p> <p>Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin.</p> <p>Results</p> <p>After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions.</p> <p>Conclusion</p> <p>There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations.</p