95 research outputs found
Load Balancing via Random Local Search in Closed and Open systems
In this paper, we analyze the performance of random load resampling and
migration strategies in parallel server systems. Clients initially attach to an
arbitrary server, but may switch server independently at random instants of
time in an attempt to improve their service rate. This approach to load
balancing contrasts with traditional approaches where clients make smart server
selections upon arrival (e.g., Join-the-Shortest-Queue policy and variants
thereof). Load resampling is particularly relevant in scenarios where clients
cannot predict the load of a server before being actually attached to it. An
important example is in wireless spectrum sharing where clients try to share a
set of frequency bands in a distributed manner.Comment: Accepted to Sigmetrics 201
A stochastic network with mobile users in heavy traffic
We consider a stochastic network with mobile users in a heavy-traffic regime.
We derive the scaling limit of the multi-dimensional queue length process and
prove a form of spatial state space collapse. The proof exploits a recent
result by Lambert and Simatos which provides a general principle to establish
scaling limits of regenerative processes based on the convergence of their
excursions. We also prove weak convergence of the sequences of stationary joint
queue length distributions and stationary sojourn times.Comment: Final version accepted for publication in Queueing Systems, Theory
and Application
On the flow-level stability of data networks without congestion control: the case of linear networks and upstream trees
In this paper, flow models of networks without congestion control are
considered. Users generate data transfers according to some Poisson processes
and transmit corresponding packet at a fixed rate equal to their access rate
until the entire document is received at the destination; some erasure codes
are used to make the transmission robust to packet losses. We study the
stability of the stochastic process representing the number of active flows in
two particular cases: linear networks and upstream trees. For the case of
linear networks, we notably use fluid limits and an interesting phenomenon of
"time scale separation" occurs. Bounds on the stability region of linear
networks are given. For the case of upstream trees, underlying monotonic
properties are used. Finally, the asymptotic stability of those processes is
analyzed when the access rate of the users decreases to 0. An appropriate
scaling is introduced and used to prove that the stability region of those
networks is asymptotically maximized
Intestinal PPARÎł signalling is required for sympathetic nervous system activation in response to caloric restriction.
Nuclear receptor PPARÎł has been proven to affect metabolism in multiple tissues, and has received considerable attention for its involvement in colon cancer and inflammatory disease. However, its role in intestinal metabolism has been largely ignored. To investigate this potential aspect of PPARÎł function, we submitted intestinal epithelium-specific PPARÎł knockout mice (iePPARÎłKO) to a two-week period of 25% caloric restriction (CR), following which iePPARÎłKO mice retained more fat than their wild type littermates. In attempting to explain this discrepancy, we analysed the liver, skeletal muscle, intestinal lipid trafficking, and the microbiome, none of which appeared to contribute to the adiposity phenotype. Interestingly, under conditions of CR, iePPARÎłKO mice failed to activate their sympathetic nervous system (SNS) and increase CR-specific locomotor activity. These KO mice also manifested a defective control of their body temperature, which was overly reduced. Furthermore, the white adipose tissue of iePPARÎłKO CR mice showed lower levels of both hormone-sensitive lipase, and its phosphorylated form. This would result from impaired SNS signalling and possibly cause reduced lipolysis. We conclude that intestinal epithelium PPARÎł plays an essential role in increasing SNS activity under CR conditions, thereby contributing to energy mobilization during metabolically stressful episodes
Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss
Background: A hypothesis exists whereby an exercise- or dietary-induced negative energy balance reduces human subcutaneous white adipose tissue (scWAT) mass through the formation of brown-like adipocyte (brite) cells. However, the validity of biomarkers of brite formation has not been robustly evaluated in humans, and clinical data that link brite formation and weight loss are sparse. Objectives: We used rosiglitazone and primary adipocytes to stringently evaluate a set of biomarkers for brite formation and determined whether the expression of biomarker genes in scWAT could explain the change in body composition in response to exercise training combined with calorie restriction in obese and overweight women (n = 79). Design: Gene expression was derived from exon DNA microarrays and preadipocytes from obesity-resistant and -sensitive mice treated with rosiglitazone to generate candidate brite biomarkers from a microarray. These biomarkers were evaluated against data derived from scWAT RNA from obese and overweight women before and after supervised exercise 5 d/wk for 16 wk combined with modest calorie restriction (âŒ0.84 MJ/d). Results: Forty percent of commonly used brite gene biomarkers exhibited an exon or strain-specific regulation. No biomarkers were positively related to weight loss in human scWAT. Greater weight loss was significantly associated with less uncoupling protein 1 expression (P = 0.006, R(2) = 0.09). In a follow-up global analysis, there were 161 genes that covaried with weight loss that were linked to greater CCAAT/enhancer binding protein α activity (z = 2.0, P = 6.6 Ă 10(â7)), liver X receptor α/ÎČ agonism (z = 2.1, P = 2.8 Ă 10(â7)), and inhibition of leptin-like signaling (z = â2.6, P = 3.9 Ă 10(â5)). Conclusion: We identify a subset of robust RNA biomarkers for brite formation and show that calorie-restrictionâmediated weight loss in women dynamically remodels scWAT to take on a more-white rather than a more-brown adipocyte phenotype
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Combined transcriptomic-(1)H NMR metabonomic study reveals yhat monoethylhexyl phthalate stimulates adipogenesis and glyceroneogenesis in human adipocytes
Adipose tissue is a major storage site for lipophilic environmental contaminants. The environmental metabolic disruptor hypothesis postulates that some pollutants can promote obesity or metabolic disorders by activating nuclear receptors involved in the control of energetic homeostasis. In this context, monoethylhexyl phthalate (MEHP) is of particular concern since it was shown to activate the peroxisome proliferator-activated receptor Îł (PPARÎł) in 3T3-L1 murine preadipocytes. In the present work, we used an untargeted, combined transcriptomic-(1)H NMR-based metabonomic approach to describe the overall effect of MEHP on primary cultures of human subcutaneous adipocytes differentiated in vitro. MEHP stimulated rapidly and selectively the expression of genes involved in glyceroneogenesis, enhanced the expression of the cytosolic phosphoenolpyruvate carboxykinase, and reduced fatty acid release. These results demonstrate that MEHP increased glyceroneogenesis and fatty acid reesterification in human adipocytes. A longer treatment with MEHP induced the expression of genes involved in triglycerides uptake, synthesis, and storage; decreased intracellular lactate, glutamine, and other amino acids; increased aspartate and NAD, and resulted in a global increase in triglycerides. Altogether, these results indicate that MEHP promoted the differentiation of human preadipocytes to adipocytes. These mechanisms might contribute to the suspected obesogenic effect of MEHP
The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice.
The gut microbiota-intestine-liver relationship is emerging as an important factor in multiple hepatic pathologies, but the hepatic sensors and effectors of microbial signals are not well defined.
By comparing publicly available liver transcriptomics data from conventional vs. germ-free mice, we identified pregnane X receptor (PXR, NR1I2) transcriptional activity as strongly affected by the absence of gut microbes. Microbiota depletion using antibiotics in Pxr <sup>+/+</sup> vs Pxr <sup>-/-</sup> C57BL/6J littermate mice followed by hepatic transcriptomics revealed that most microbiota-sensitive genes were PXR-dependent in the liver in males, but not in females. Pathway enrichment analysis suggested that microbiota-PXR interaction controlled fatty acid and xenobiotic metabolism. We confirmed that antibiotic treatment reduced liver triglyceride content and hampered xenobiotic metabolism in the liver from Pxr <sup>+/+</sup> but not Pxr <sup>-/-</sup> male mice.
These findings identify PXR as a hepatic effector of microbiota-derived signals that regulate the host's sexually dimorphic lipid and xenobiotic metabolisms in the liver. Thus, our results reveal a potential new mechanism for unexpected drug-drug or food-drug interactions. Video abstract
OptiJ: Open-source optical projection tomography of large organ samples
The three-dimensional imaging of mesoscopic samples with Optical Projection Tomography (OPT) has become a powerful tool for biomedical phenotyping studies. OPT uses visible light to visualize the 3D morphology of large transparent samples. To enable a wider application of OPT, we present OptiJ, a low-cost, fully open-source OPT system capable of imaging large transparent specimens up to 13âmm tall and 8âmm deep with 50â”m resolution. OptiJ is based on off-the-shelf, easy-to-assemble optical components and an ImageJ plugin library for OPT data reconstruction. The software includes novel correction routines for uneven illumination and sample jitter in addition to CPU/GPU accelerated reconstruction for large datasets. We demonstrate the use of OptiJ to image and reconstruct cleared lung lobes from adult mice. We provide a detailed set of instructions to set up and use the OptiJ framework. Our hardware and software design are modular and easy to implement, allowing for further open microscopy developments for imaging large organ samples
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Structural and dynamic disorder, not ionic trapping, controls charge transport in highly doped conducting polymers
Doped organic semiconductors are critical to emerging device applications,
including thermoelectrics, bioelectronics, and neuromorphic computing devices.
It is commonly assumed that low conductivities in these materials result
primarily from charge trapping by the Coulomb potentials of the dopant
counter-ions. Here, we present a combined experimental and theoretical study
rebutting this belief. Using a newly developed doping technique, we find the
conductivity of several classes of high-mobility conjugated polymers to be
strongly correlated with paracrystalline disorder but poorly correlated with
ionic size, suggesting that Coulomb traps do not limit transport. A general
model for interacting electrons in highly doped polymers is proposed and
carefully parameterized against atomistic calculations, enabling the
calculation of electrical conductivity within the framework of transient
localisation theory. Theoretical calculations are in excellent agreement with
experimental data, providing insights into the disordered-limited nature of
charge transport and suggesting new strategies to further improve
conductivities
Structural and dynamic disorder, not ionic trapping, controls charge transport in highly doped conducting polymers
Doped organic semiconductors are critical to emerging device applications,
including thermoelectrics, bioelectronics, and neuromorphic computing devices.
It is commonly assumed that low conductivities in these materials result
primarily from charge trapping by the Coulomb potentials of the dopant
counter-ions. Here, we present a combined experimental and theoretical study
rebutting this belief. Using a newly developed doping technique, we find the
conductivity of several classes of high-mobility conjugated polymers to be
strongly correlated with paracrystalline disorder but poorly correlated with
ionic size, suggesting that Coulomb traps do not limit transport. A general
model for interacting electrons in highly doped polymers is proposed and
carefully parameterized against atomistic calculations, enabling the
calculation of electrical conductivity within the framework of transient
localisation theory. Theoretical calculations are in excellent agreement with
experimental data, providing insights into the disordered-limited nature of
charge transport and suggesting new strategies to further improve
conductivities
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