Context switching accounting mechanism

How many times a given process p preempts, either voluntarily or involuntarily, is an important threat to computer's processes throughput. Whenever running cpu-bound processes on a multi-core system without an actual system grid engine as commonly found on Grid Clusters, their performance and stability are directly related to their accurate implementation and the system reliability which is, to an extend, an important caveat most of the times so difficult to detect. Context Switching is time-consuming. Thus, if we could develop a tool capable of detecting it and gather data from every single performed Context Switch, we would beable to study this data and present some results that should pin-point at whatever their main cause could be.

Thread Scheduling Mechanisms for Multiple-Context Parallel Processors

Scheduling tasks to efficiently use the available processor resources is crucial to minimizing the runtime of applications on shared-memory parallel processors. One factor that contributes to poor processor utilization is the idle time caused by long latency operations, such as remote memory references or processor synchronization operations. One way of tolerating this latency is to use a processor with multiple hardware contexts that can rapidly switch to executing another thread of computation whenever a long latency operation occurs, thus increasing processor utilization by overlapping computation with communication. Although multiple contexts are effective for tolerating latency, this effectiveness can be limited by memory and network bandwidth, by cache interference effects among the multiple contexts, and by critical tasks sharing processor resources with less critical tasks. This thesis presents techniques that increase the effectiveness of multiple contexts by intelligently scheduling threads to make more efficient use of processor pipeline, bandwidth, and cache resources. This thesis proposes thread prioritization as a fundamental mechanism for directing the thread schedule on a multiple-context processor. A priority is assigned to each thread either statically or dynamically and is used by the thread scheduler to decide which threads to load in the contexts, and to decide which context to switch to on a context switch. We develop a multiple-context model that integrates both cache and network effects, and shows how thread prioritization can both maintain high processor utilization, and limit increases in critical path runtime caused by multithreading. The model also shows that in order to be effective in bandwidth limited applications, thread prioritization must be extended to prioritize memory requests. We show how simple hardware can prioritize the running of threads in the multiple contexts, and the issuing of requests to both the local memory and the network. Simulation experiments show how thread prioritization is used in a variety of applications. Thread prioritization can improve the performance of synchronization primitives by minimizing the number of processor cycles wasted in spinning and devoting more cycles to critical threads. Thread prioritization can be used in combination with other techniques to improve cache performance and minimize cache interference between different working sets in the cache. For applications that are critical path limited, thread prioritization can improve performance by allowing processor resources to be devoted preferentially to critical threads. These experimental results show that thread prioritization is a mechanism that can be used to implement a wide range of scheduling policies.

Comparative study and identification of potent eukaryotic transcriptional repressors in gene switch systems.

In mammalian cells, proper gene regulation is achieved by the complex interplay of transcription factors that activate or repress gene expression by binding to the regulatory regions of target promoters. While transcriptional activators have been extensively characterised and classified into functional groups, relatively little is known about the comparative strength and cell type-specificity of transcriptional repressors. Here, we have compared the ability of a series of eukaryotic repression domains to silence basal and activated transcription. A series of the most potent repression domains was further tested in the context of a gene therapy gene-switch system in various cell types. The results indicate that the analysed repression domains exert varying silencing activities in different promoter contexts. Furthermore, their potential for gene silencing varies also depending on the cellular context. When multimerised within one chimeric repressor protein, particular combinations of repressor domains were found to display synergistic repressing effects and efficient repression in a panel of cell lines. This approach thus allowed the identification of transcriptional repressors that are both potent and versatile in terms of cellular specificity as a basis for gene switch systems.

Optimization of Amplifier Placements in Switch-Based Optical Networks

Wavelength division multiplexing (WDM) offers a solution to the problem of exploiting the large bandwidth on optical links; it is the current favorite multiplexing technology for optical communication networks. Due to the high cost of an optical amplifier, it is desirable to strategically place the amplifiers throughout the network in a way that guarantees that all the signals are adequately amplified while minimizing the total number amplifiers being used. Previous studies all consider a star-based network. This paper demonstrates an original approach for solving the problem in switch-based WDM optical network assuming the traffic matrix is always the permutation of the nodes. First we formulate the problem by choosing typical permutations which can maximize traffic load on individual links; then a GA (Genetic Algorithm) is used to search for feasible amplifier placements. Finally, by setting up all the lightpaths without violating the power constaints we confirm the feasibility of the solution.

The function of secretory IgA in the context of the intestinal continuum of adaptive immune responses in host-microbial mutualism

The large production of immunoglobulin (Ig)A is energetically costly. The fact that evolution retained this apparent luxury of intestinal class switch recombination to IgA within the human population strongly indicates that there must be a critical specific function of IgA for survival of the species. The function of IgA has been investigated in a series of different models that will be discussed here. While IgA has clear protective functions against toxins or in the context of intestinal viral infections, the function of IgA specific for non-pathogenic commensal bacteria remains unclear. In the context of the current literature we present a hypothesis where secretory IgA integrates as an additional layer of immune function into the continuum of intestinal CD4 T cell responses, to achieve a mutualistic relationship between the intestinal commensal microbiota and the host.

Cannabinoid receptor trafficking in peripheral cells is dynamically regulated by a binary biochemical switch

The cannabinoid G protein-coupled receptors (GPCRs) CB₁ and CB₂ are expressed in different peripheral cells. Localization of GPCRs in the cell membrane determines signaling via G protein pathways. Here we show that unlike in transfected cells, CB receptors in cell lines and primary human cells are not internalized upon agonist interaction, but move between cytoplasm and cell membranes by ligand-independent trafficking mechanisms. Even though CB receptors are expressed in many cells of peripheral origin they are not always localized in the cell membrane and in most cancer cell lines the ratios between CB₁ and CB₂ receptor gene and surface expression vary significantly. In contrast, CB receptor cell surface expression in HL60 cells is subject to significant oscillations and CB₂ receptors form oligomers and heterodimers with CB₁ receptors, showing synchronized surface expression, localization and trafficking. We show that hydrogen peroxide and other nonspecific protein tyrosine phosphatase inhibitors (TPIs) such as phenylarsine oxide trigger both CB₂ receptor internalization and externalization, depending on receptor localization. Phorbol ester-mediated internalization of CB receptors can be inhibited via this switch. In primary human immune cells hydrogen peroxide and other TPIs lead to a robust internalization of CB receptors in monocytes and an externalization in T cells. This study describes, for the first time, the dynamic nature of CB receptor trafficking in the context of a biochemical switch, which may have implications for studies on the cell-type specific effects of cannabinoids and our understanding of the regulation of CB receptor cell surface expression.

SUMO-SPECIFIC PROTEASE 1 CONTROLS LYMPHOID DEVELOPMENT THROUGH REGULATION OF SUMOYLATION/ACETYLATION SWITCH IN STAT5

SUMOylation has emerged as an important regulatory mechanism for protein function. SUMO-specific proteases (SENPs) are essential for removing SUMO from conjugated proteins in many different systems, but the physiological functions of SENPs are poorly understood. STAT5 (Signal Transducer and Activator of Transcription 5) plays a critical role in the development of lymphoid cells. However, it is not known whether STAT5 is regulated by the SUMOylation pathway. Here, we showed that SUMOylated STAT5 is accumulated in SENP1-/- lymphoid precursors. SENP1 deficiency results in severe defects in early T and B cell development, similar to that observed in mice harboring a complete inactivation of STAT5. Because STAT5 is SUMOylated and acetylated at the same lysine residue, SENP1 deficiency blocks STAT5 in the SUMOylation state, resulting in diminished STAT5 acetylation and phosphorylation, and defective lymphoid development. Thus, our results reveal a novel function of SENP1 in the regulation of early lymphoid development via an acetylation/SUMOylation switch in STAT5.

14-3-3 ZETA OVEREXPRESSION SERVES AS A NOVEL MOLECULAR SWITCH TURNING TGF-BETA FROM TUMOR SUPPRESSOR TO TUMOR PROMOTER

TGF-β plays an important role in differentiation and tissue morphogenesis as well as cancer progression. However, the role of TGF-β in cancer is complicate. TGF-β has primarily been recognized as tumor suppressor, because it can directly inhibit cell proliferation of normal and premalignant epithelial cell. However, in the last stage of tumor progression, TGF-β functions as tumor promoter to enhance tumor cells metastatic dissemination and expands metastatic colonies. Currently, the mechanism of how TGF-β switches its role from tumor suppressor to promoter still remains elusive. Here we identify that overexpression of 14-3-3ζ inhibits TGF-β’s cell cytostatic program through destabilizing p53 in non-transformed human mammary epithelial cells. Mechanistically, we found that 14-3-3ζ overexpression leads to 14-3-3σ downregulation, thereby activates PI3K/Akt signaling pathway and degrades p53, and further inhibits TGF-β induced p21 expression and cell cytostatic function. In addition, we found that overexpression of 14-3-3ζ promotes TGF-β induced breast cancer cells bone metastatic colonization through stabilizing Gli2, which is an important co-transcriptional factor for p-smad2 to activate PTHrP expression and bone osteolytic effect. Taken together, we reveal a novel mechanism that 14-3-3ζ dictates the tumor suppressor or metastases promoter activities of TGF-β signaling pathway through switching p-smad2 binding partner from p53 to Gli2. The expected results will not only provide us the better understanding of the important role of 14-3-3ζ in the early stage of breast cancer development, but also deeply impact our knowledge of signaling mechanisms underlying the complex roles of TGF-β in cancer, which will give us a more accurate strategy to determine when and how anti-TGF-β targeted therapy might be effective.

Evaluating the equity effects of road-pricing in the European urban context - The Madrid Metropolitan Area

The paper identifies the potential spatial and social impacts of a proposed road-pricing scheme for different social groups in the Madrid Metropolitan Area (MMA). We appraise the accessibility of different districts within the MMA in terms of the actual and perceived cost of using the road infrastructure ‘before’ and ‘after’ implementation of the scheme. The appraisal framework was developed using quantitative survey data and qualitative focus group discussions with residents. We then simulated user behaviours (mode and route choice) based on the empirical evidence from a travel demand model for the MMA. The results from our simulation model demonstrated that implementation of the toll on the orbital metropolitan motorways (M40, M30, for example) decreases accessibility mostly in the districts where there are no viable public transport alternatives. Our specific study finding is that the economic burden of the road-pricing scheme particularly affects unskilled and lower income individuals living in the south of the MMA. The focus groups confirmed that low income drivers in the south part of the MMA would reduce their use of tolled roads and have to find new arrangements for these trips: i.e. switch to public transport, spend double the time travelling or stay at home. More generally, our research finds that European transport planners are still a long way from recognising the social equity implications of their policy decisions and that more thorough social appraisals are needed to avoid the social exclusion of low income populations when road tolling is proposed.

Evaluating the spatial and social equity effects of road pricing in the European urban context: the Madrid Metropolitan Area.

The paper explores the spatial and social impacts arising from implementation of a road-pricing scheme in the Madrid Metropolitan Area (MMA). Our analytical focus is on understanding the effects of the scheme on the transport accessibility of different social groups within the MMA. We define an evaluation framework to appraise the accessibility of different districts within the MMA in terms of the actual and perceived cost of using the road infrastructure "before" and "after" the implementation of the scheme. The framework was developed using quantitative survey data and qualitative data from focus group discussions with residents. We then simulated user behaviors (mode and route choice) based on the empirical evidence from a travel demand model for the MMA. The results from our simulation model demonstrated that implementation of the toll on the orbital metropolitan motorways (M40, M30, for example) decreases accessibility, mostly in the districts where there are no viable public transport alternatives. Our key finding is that the economic burden of the road-pricing scheme particularly affects unskilled and lower income individuals living in the south of the MMA. Consequently lower income people reduce their use of tolled roads and have to find new arrangements for these trips: i.e. switch to the public transport, spend double the time for their commuter trips or stay at home. The results of our research could be applicable more widely for anyone wishing to better understand the important relationship between increased transport cost and social equity, especially where there is an intention to introduce similar road-pricing schemes within the urban context.

Dual-function regulators: the cAMP receptor protein and the CytR regulator can act either to repress or to activate transcription depending on the context.

Studies of gene regulation have revealed that several transcriptional regulators can switch between activator and repressor depending upon both the promoter and the cellular context. A relatively simple prokaryotic example is illustrated by the Escherichia coli CytR regulon. In this system, the cAMP receptor protein (CRP) assists the binding of RNA polymerase as well as a specific negative regulator, CytR. Thus, CRP functions either as an activator or as a corepressor. Here we show that, depending on promoter architecture, the CRP/CytR nucleoprotein complex has opposite effects on transcription. When acting from a site close to the DNA target for RNA polymerase, CytR interacts with CRP to repress transcription, whereas an interaction with CRP from appropriately positioned upstream binding sites can result in formation of a huge preinitiation complex and transcriptional activation. Based on recent results about CRP-mediated regulation of transcription initiation and the finding that CRP possesses discrete surface-exposed patches for protein-protein interaction with RNA polymerase and CytR, a molecular model for this dual regulation is discussed.

Deployment of a Hybrid Multicast Switch in Energy-Aware Data Center Network: A Case of Fat-Tree Topology

Recently, energy efficiency or green IT has become a hot issue for many IT infrastructures as they attempt to utilize energy-efficient strategies in their enterprise IT systems in order to minimize operational costs. Networking devices are shared resources connecting important IT infrastructures, especially in a data center network they are always operated 24/7 which consume a huge amount of energy, and it has been obviously shown that this energy consumption is largely independent of the traffic through the devices. As a result, power consumption in networking devices is becoming more and more a critical problem, which is of interest for both research community and general public. Multicast benefits group communications in saving link bandwidth and improving application throughput, both of which are important for green data center. In this paper, we study the deployment strategy of multicast switches in hybrid mode in energy-aware data center network: a case of famous fat-tree topology. The objective is to find the best location to deploy multicast switch not only to achieve optimal bandwidth utilization but also to minimize power consumption. We show that it is possible to easily achieve nearly 50% of energy consumption after applying our proposed algorithm.

A Thermally Wavelength-tunable Photonic Switch Based on Silicon Microring Resonator

Silicon photonics is a very promising technology for future low-cost high-bandwidth optical telecommunication applications down to the chip level. This is due to the high degree of integration, high optical bandwidth and large speed coupled with the development of a wide range of integrated optical functions. Silicon-based microring resonators are a key building block that can be used to realize many optical functions such as switching, multiplexing, demultiplaxing and detection of optical wave. The ability to tune the resonances of the microring resonators is highly desirable in many of their applications. In this work, the study and application of a thermally wavelength-tunable photonic switch based on silicon microring resonator is presented. Devices with 10µm diameter were systematically studied and used in the design. Its resonance wavelength was tuned by thermally induced refractive index change using a designed local micro-heater. While thermo-optic tuning has moderate speed compared with electro-optic and all-optic tuning, with silicon’s high thermo-optic coefficient, a much wider wavelength tunable range can be realized. The device design was verified and optimized by optical and thermal simulations. The fabrication and characterization of the device was also implemented. The microring resonator has a measured FSR of ~18 nm, FWHM in the range 0.1-0.2 nm and Q around 10,000. A wide tunable range (>6.4 nm) was achieved with the switch, which enables dense wavelength division multiplexing (DWDM) with a channel space of 0.2nm. The time response of the switch was tested on the order of 10 us with a low power consumption of ~11.9mW/nm. The measured results are in agreement with the simulations. Important applications using the tunable photonic switch were demonstrated in this work. 1×4 and 4×4 reconfigurable photonic switch were implemented by using multiple switches with a common bus waveguide. The results suggest the feasibility of on-chip DWDM for the development of large-scale integrated photonics. Using the tunable switch for output wavelength control, a fiber laser was demonstrated with Erbium-doped fiber amplifier as the gain media. For the first time, this approach integrated on-chip silicon photonic wavelength control.

Reasons For Brazilian Women To Switch From Different Contraceptives To Long-acting Reversible Contraceptives.

Long-acting reversible contraceptives (LARCs) include the copper-releasing intrauterine device (IUD), the levonorgestrel-releasing intrauterine system (LNG-IUS) and implants. Despite the high contraceptive efficacy of LARCs, their prevalence of use remains low in many countries. The objective of this study was to assess the main reasons for switching from contraceptive methods requiring daily or monthly compliance to LARC methods within a Brazilian cohort. Women of 18-50 years of age using different contraceptives and wishing to switch to a LARC method answered a questionnaire regarding their motivations for switching from their current contraceptive. Continuation rates were evaluated 1 year after method initiation. Sample size was calculated at 1040 women. Clinical performance was evaluated by life table analysis. The cutoff date for analysis was May 23, 2013. Overall, 1167 women were interviewed; however, after 1 year of use, the medical records of only 1154 women were available for review. The main personal reason for switching, as reported by the women, was fear of becoming pregnant while the main medical reasons were nausea and vomiting and unscheduled bleeding. No pregnancies occurred during LARC use, and the main reasons for discontinuation were expulsion (in the case of the IUD and LNG-IUS) and a decision to undergo surgical sterilization (in the case of the etonogestrel-releasing implant). Continuation rate was ~95.0/100 women/year for the three methods. Most women chose a LARC method for its safety and for practical reasons, and after 1 year of use, most women continued with the method.

Understanding Red Blood Cell Parameters In The Context Of The Frailty Phenotype: Interpretations Of The Fibra (frailty In Brazilian Seniors) Study.

Frailty and anemia in the elderly appear to share a common pathophysiology associated with chronic inflammatory processes. This study uses an analytical, cross-sectional, population-based methodology to investigate the probable relationships between frailty, red blood cell parameters and inflammatory markers in 255 community-dwelling elders aged 65 years or older. The frailty phenotype was assessed by non-intentional weight loss, fatigue, low grip strength, low energy expenditure and reduced gait speed. Blood sample analyses were performed to determine hemoglobin level, hematocrit and reticulocyte count, as well as the inflammatory variables IL-6, IL-1ra and hsCRP. In the first multivariate analysis (model I), considering only the erythroid parameters, Hb concentration was a significant variable for both general frailty status and weight loss: a 1.0g/dL drop in serum Hb concentration represented a 2.02-fold increase (CI 1.12-3.63) in an individual's chance of being frail. In the second analysis (model II), which also included inflammatory cytokine levels, hsCRP was independently selected as a significant variable. Each additional year of age represented a 1.21-fold increase in the chance of being frail, and each 1-unit increase in serum hsCRP represented a 3.64-fold increase in the chance of having the frailty phenotype. In model II reticulocyte counts were associated with weight loss and reduced metabolic expenditure criteria. Our findings suggest that reduced Hb concentration, reduced RetAbs count and elevated serum hsCRP levels should be considered components of frailty, which in turn is correlated with sarcopenia, as evidenced by weight loss.