bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Smoothed Analysis of Multiobjective Optimization
Authors: Brunsch Tobias , Röglin Heiko
Published: March 2015

We present several new results about smoothed analysis of multiobjective optimization problems. Motivated by the discrepancy between worst-case analysis and practical experience, this line of research has gained a lot of attention in the last decade. We consider problems in which
d
linear and one arbitrary objective function are to be optimized over a set
S
⊆ {0, 1}

n

of feasible solutions. We improve the previously best known bound for the smoothed number of Pareto-optimal solutions to
O
(
n

2
d

φ

d

), where φ denotes the perturbation parameter. Additionally, we show that for any constant
c
the
c
th moment of the smoothed number of Pareto-optimal solutions is bounded by
O
((
n

2
d

φ

d

)

c

). This improves the previously best known bounds significantly.

Furthermore, we address the criticism that the perturbations in smoothed analysis destroy the zero-structure of problems by showing that the smoothed number of Pareto-optimal solutions remains polynomially bounded even for zero-preserving perturbations. This broadens the class of problems captured by smoothed analysis and it has consequences for nonlinear objective functions. One corollary of our result is that the smoothed number of Pareto-optimal solutions is polynomially bounded for polynomial objective functions. Our results also extend to integer optimization problems.
Marching-Based Wear-Leveling for PCM-Based Storage Systems
Authors: Chang Hung-Sheng , Chang Yuan-Hao , Hsiu Pi-Cheng , Kuo Tei-Wei , Li Hsiang-Pang
Published: March 2015

Improving the performance of storage systems without losing the reliability and sanity/integrity of file systems is a major issue in storage system designs. In contrast to existing storage architectures, we consider a PCM-based storage architecture to enhance the reliability of storage systems. In PCM-based storage systems, the major challenge falls on how to prevent the frequently updated (meta)data from wearing out their residing PCM cells without excessively searching and moving metadata around the PCM space and without extensively updating the index structures of file systems. In this work, we propose an adaptive wear-leveling mechanism to prevent any PCM cell from being worn out prematurely by selecting appropriate data for swapping with constant search/sort cost. Meanwhile, the concept of indirect pointers is designed in the proposed mechanism to swap data without any modification to the file system's indexes. Experiments were conducted based on well-known benchmarks and realistic workloads to evaluate the effectiveness of the proposed design, for which the results are encouraging.
The Design and Experiments of A SID-Based Power-Aware Simulator for Embedded Multicore Systems
Authors: Lin Cheng-Yen , Huang Chung-Wen , Kuan Chi-Bang , Huang Shi-Yu , Lee Jenq-Kuen
Published: March 2015

Embedded multicore systems are playing increasingly important roles in the design of consumer electronics. The objective of such systems is to optimize both performance and power characteristics of mobile devices. However, currently there are no power metrics supporting popular application design platforms (such as SID) that application developers use to develop their applications. This hinders the ability of application developers to optimize power consumption. In this article we present the design and experiments of a SID-based power-aware simulation framework for embedded multicore systems. The proposed power estimation flow includes two phases: IP-level power modeling and power-aware system simulation. The first phase employs PowerMixer

IP

to construct the power model for the processor IP and other major IPs, while the second phase involves a power abstract interpretation method for summarizing the simulation trace, then, with a CPE module, estimating the power consumption based on the summarized trace information and the input of IP power models. In addition, a
Manager
component is devised to map each digital signal processor (DSP) component to a host thread and maintain the access to shared resources. The aim is to maintain the simulation performance as the number of simulated DSP components increases. A power-profiling API is also supported that developers of embedded software can use to tune the granularity of power-profiling for a specific code section of the target application. We demonstrate via case studies and experiments how application developers can use our SID-based power simulator for optimizing the power consumption of their applications. We characterize the power consumption of DSP applications with the DSPstone benchmark and discuss how compiler optimization levels with SIMD intrinsics influence the performance and power consumption. A histogram application and an augmented-reality application based on human-face-based RMS (recognition, mining, and synthesis) application are deployed as running examples on multicore systems to demonstrate how our power simulator can be used by developers in the optimization process to illustrate different views of power dissipations of applications.
DualMOP-RPL
Authors: Ko Jeonggil , Jeong Jongsoo , Park Jongjun , Jun Jong Arm , Gnawali Omprakash , Paek Jeongyeup
Published: March 2015

RPL is an IPv6 routing protocol for low-power and lossy networks (LLNs) designed to meet the requirements of a wide range of LLN applications including smart grid AMIs, home and building automation, industrial and environmental monitoring, health care, wireless sensor networks, and the Internet of Things (IoT) in general with thousands and millions of nodes interconnected through multihop mesh networks. RPL constructs tree-like routing topology rooted at an LLN border router (LBR) and supports bidirectional IPv6 communication to and from the mesh devices by providing both upward and downward routing over the routing tree. In this article, we focus on the interoperability of downward routing and supporting its two modes of operations (MOPs) defined in the RPL standard (RFC 6550). Specifically, we show that there exists a serious connectivity problem in RPL protocol when two MOPs are mixed within a single network, even for standard-compliant implementations, which may result in network partitions. To address this problem, this article proposes
DualMOP-RPL
, an enhanced version of RPL, which supports nodes with different MOPs for downward routing to communicate gracefully in a single RPL network while preserving the high bidirectional data delivery performance.
DualMOP-RPL
allows multiple overlapping RPL networks in the same geographical regions to cooperate as a single densely connected network even if those networks are using different MOPs. This will not only improve the link qualities and routing performances of the networks but also allow for network migrations and alternate routing in the case of LBR failures. We evaluate
DualMOP-RPL
through extensive simulations and testbed experiments and show that our proposal eliminates all the problems we have identified.
Optimal Selection of Adaptive Streaming Representations
Authors: Toni Laura , Aparicio-Pardo Ramon , Pires Karine , Simon Gwendal , Blanc Alberto , Frossard Pascal
Published: March 2015

Adaptive streaming addresses the increasing and heterogeneous demand of multimedia content over the Internet by offering several encoded versions for each video sequence. Each version (or representation) is characterized by a resolution and a bit rate, and it is aimed at a specific set of users, like TV or mobile phone clients. While most existing works on adaptive streaming deal with effective playout-buffer control strategies on the client side, in this article we take a providers' perspective and propose solutions to improve user satisfaction by optimizing the set of available representations. We formulate an integer linear program that maximizes users' average satisfaction, taking into account network dynamics, type of video content, and user population characteristics. The solution of the optimization is a set of encoding parameters corresponding to the representations set that maximizes user satisfaction. We evaluate this solution by simulating multiple adaptive streaming sessions characterized by realistic network statistics, showing that the proposed solution outperforms commonly used vendor recommendations, in terms of user satisfaction but also in terms of fairness and outage probability. The simulation results show that video content information as well as network constraints and users' statistics play a crucial role in selecting proper encoding parameters to provide fairness among users and to reduce network resource usage. We finally propose a few theoretical guidelines that can be used, in realistic settings, to choose the encoding parameters based on the user characteristics, the network capacity and the type of video content.
QUAL
Authors: Baillie Chris , Edwards Peter , Pignotti Edoardo
Published: March 2015

In this article, we present a model for quality assessment over linked data. This model has been designed to align with emerging standards for provenance on the Web to enable agents to reason about data provenance when performing quality assessment. The model also enables quality assessment provenance to be represented, thus allowing agents to make decisions about reuse of existing assessments. We also discuss the development of an OWL ontology as part of a software framework to support reasoning about data quality and assessment reuse. Finally, we evaluate this framework using two real-world case studies derived from transport and invasive-species monitoring applications.
Anisotropic Delaunay Meshes of Surfaces
Authors: Boissonnat Jean-Daniel , Shi Kan-Le , Tournois Jane , Yvinec Mariette
Published: March 2015

Anisotropic simplicial meshes are triangulations with elements elongated along prescribed directions. Anisotropic meshes have been shown well suited for interpolation of functions or solving PDEs. They can also significantly enhance the accuracy of a surface representation. Given a surface
S
endowed with a metric tensor field, we propose a new approach to generate an anisotropic mesh that approximates
S
with elements shaped according to the metric field. The algorithm relies on the well-established concepts of restricted Delaunay triangulation and Delaunay refinement and comes with theoretical guarantees. The star of each vertex in the output mesh is Delaunay for the metric attached to this vertex. Each facet has a good aspect ratio with respect to the metric specified at any of its vertices. The algorithm is easy to implement. It can mesh various types of surfaces like implicit surfaces, polyhedra, or isosurfaces in 3D images. It can handle complicated geometries and topologies, and very anisotropic metric fields.
Demo hour
Authors: Rheiner Max , Tobler Thomas , Troxler Fabian , Inoue Seki , Hasegawa Keisuke , Monnai Yasuaki , Makino Yasutoshi , Shinoda Hiroyuki , Françoise Jules , Schnell Norbert , Borghesi Riccardo , Bevilacqua Frédéric , Cakmak Tuncay , Hager Holger
Published: March 2015

At SIGGRAPH 2014, the Emerging Technologies venue presented installations stemming from several fields, including displays, input devices, collaborative environments, robotics, haptics, and simulators. Of the 26 displayed installations at the conference (Vancouver, Canada, Aug. 10--14, 2014), we have selected the following four that highlight today's trends in technology and usage innovation. Thierry Frey, SIGGRAPH 2014 Emerging Technologies Chair
Millions of little minions
Authors: Jeyakumar Vimalkumar , Alizadeh Mohammad , Geng Yilong , Kim Changhoon , Mazières David
Published: March 2015

This paper presents a practical approach to rapidly introducing new dataplane functionality into networks: End-hosts embed tiny programs into packets to actively query and manipulate a network's internal state. We show how this "tiny packet program" (TPP) interface gives end-hosts unprecedented visibility into network behavior, enabling them to work with the network to achieve a desired functionality. Our design leverages what each component does best: (a) switches forward and execute tiny packet programs (at most 5~instructions) in-band at line rate, and (b) end-hosts perform arbitrary (and easily updated) computation on network state. By implementing three different research proposals, we show that TPPs are useful. Using a hardware prototype on a NetFPGA, we show our design is feasible at a reasonable cost.
From the consent of the routed
Authors: Heilman Ethan , Cooper Danny , Reyzin Leonid , Goldberg Sharon
Published: March 2015

The Resource Public Key Infrastructure (RPKI) is a new infrastructure that prevents some of the most devastating attacks on interdomain routing. However, the security benefits provided by the RPKI are accomplished via an architecture that empowers centralized authorities to unilaterally revoke any IP prefixes under their control. We propose mechanisms to improve the transparency of the RPKI, in order to mitigate the risk that it will be used for IP address takedowns. First, we present tools that detect and visualize changes to the RPKI that can potentially take down an IP prefix. We use our tools to identify errors and revocations in the production RPKI. Next, we propose modifications to the RPKI's architecture to (1) require any revocation of IP address space to receive consent from all impacted parties, and (2) detect when misbehaving authorities fail to obtain consent. We present a security analysis of our architecture, and estimate its overhead using data-driven analysis.
Measuring IPv6 adoption
Authors: Czyz Jakub , Allman Mark , Zhang Jing , Iekel-Johnson Scott , Osterweil Eric , Bailey Michael
Published: March 2015

After several IPv4 address exhaustion milestones in the last three years, it is becoming apparent that the world is running out of IPv4 addresses, and the adoption of the next generation Internet protocol, IPv6, though nascent, is accelerating. In order to better understand this unique and disruptive transition, we explore twelve metrics using ten global-scale datasets to create the longest and broadest measurement of IPv6 adoption to date. Using this perspective, we find that adoption, relative to IPv4, varies by two orders of magnitude depending on the measure examined and that care must be taken when evaluating adoption metrics in isolation. Further, we find that regional adoption is not uniform. Finally, and perhaps most surprisingly, we find that over the last three years, the nature of IPv6 utilization-in terms of traffic, content, reliance on transition technology, and performance-has shifted dramatically from prior findings, indicating a maturing of the protocol into production mode. We believe IPv6's recent growth and this changing utilization signal a true quantum leap.
Troubleshooting blackbox SDN control software with minimal causal sequences
Authors: Scott Colin , Wundsam Andreas , Raghavan Barath , Panda Aurojit , Or Andrew , Lai Jefferson , Huang Eugene , Liu Zhi , El-Hassany Ahmed , Whitlock Sam , Acharya H.B. , Zarifis Kyriakos , Shenker Scott
Published: March 2015

Software bugs are inevitable in software-defined networking control software, and troubleshooting is a tedious, time-consuming task. In this paper we discuss how to improve control software troubleshooting by presenting a technique for automatically identifying a minimal sequence of inputs responsible for triggering a given bug, without making assumptions about the language or instrumentation of the software under test. We apply our technique to five open source SDN control platforms---Floodlight, NOX, POX, Pyretic, ONOS---and illustrate how the minimal causal sequences our system found aided the troubleshooting process.
Duet
Authors: Gandhi Rohan , Liu Hongqiang Harry , Hu Y. Charlie , Lu Guohan , Padhye Jitendra , Yuan Lihua , Zhang Ming
Published: March 2015

Load balancing is a foundational function of datacenter infrastructures and is critical to the performance of online services hosted in datacenters. As the demand for cloud services grows, expensive and hard-to-scale dedicated hardware load balancers are being replaced with software load balancers that scale using a distributed data plane that runs on commodity servers. Software load balancers offer low cost, high availability and high flexibility, but suffer high latency and low capacity per load balancer, making them less than ideal for applications that demand either high throughput, or low latency or both. In this paper, we present Duet, which offers all the benefits of software load balancer, along with low latency and high availability -- at next to no cost. We do this by exploiting a hitherto overlooked resource in the data center networks -- the switches themselves. We show how to embed the load balancing functionality into existing hardware switches, thereby achieving organic scalability at no extra cost. For flexibility and high availability, Duet seamlessly integrates the switch-based load balancer with a small deployment of software load balancer. We enumerate and solve several architectural and algorithmic challenges involved in building such a hybrid load balancer. We evaluate Duet using a prototype implementation, as well as extensive simulations driven by traces from our production data centers. Our evaluation shows that Duet provides 10x more capacity than a software load balancer, at a fraction of a cost, while reducing latency by a factor of 10 or more, and is able to quickly adapt to network dynamics including failures.
Lightweight source authentication and path validation
Authors: Kim Tiffany Hyun-Jin , Basescu Cristina , Jia Limin , Lee Soo Bum , Hu Yih-Chun , Perrig Adrian
Published: March 2015

In-network source authentication and path validation are fundamental primitives to construct higher-level security mechanisms such as DDoS mitigation, path compliance, packet attribution, or protection against flow redirection. Unfortunately, currently proposed solutions either fall short of addressing important security concerns or require a substantial amount of router overhead. In this paper, we propose lightweight, scalable, and secure protocols for shared key setup, source authentication, and path validation. Our prototype implementation demonstrates the efficiency and scalability of the protocols, especially for software-based implementations.
RF-IDraw
Authors: Wang Jue , Vasisht Deepak , Katabi Dina
Published: March 2015

Prior work in RF-based positioning has mainly focused on discovering the absolute location of an RF source, where state-of-the-art systems can achieve an accuracy on the order of tens of centimeters using a large number of antennas. However, many applications in gaming and gesture based interface see more benefits in knowing the detailed shape of a motion. Such trajectory tracing requires a resolution several fold higher than what existing RF-based positioning systems can offer.

This paper shows that one can provide a dramatic increase in trajectory tracing accuracy, even with a small number of antennas. The key enabler for our design is a multi-resolution positioning technique that exploits an intrinsic tradeoff between improving the resolution and resolving ambiguity in the location of the RF source. The unique property of this design is its ability to precisely reconstruct the minute details in the trajectory shape, even when the absolute position might have an offset. We built a prototype of our design with commercial off-the-shelf RFID readers and tags and used it to enable a virtual touch screen, which allows a user to interact with a desired computing device by gesturing or writing her commands in the air, where each letter is only a few centimeters wide.
OpenANFV
Authors: Ge Xiongzi , Liu Yi , Du David H.C. , Zhang Liang , Guan Hongguang , Chen Jian , Zhao Yuping , Hu Xinyu
Published: March 2015

The resources of dedicated accelerators (e.g. FPGA) are still required to bridge the gap between software-based Middleboxs(MBs) and the commodity hardware. To consolidate various hardware resources in an elastic, programmable and reconfigurable manner, we design and build a flexible and consolidated framework, OpenANFV, to support virtualized accelerators for MBs in the cloud environment. OpenANFV is seamlessly and efficiently put into Openstack to provide high performance on top of commodity hardware to cope with various virtual function requirements. OpenANFV works as an independent component to manage and virtualize the acceleration resources (e.g. cinder manages block storage resources and nova manages computing resources). Specially, OpenANFV mainly has the following three features. (1)Automated Management. Provisioning for multiple Virtualized Network Functions (VNFs) is automated to meet the dynamic requirements of NFV environment. Such automation alleviates the time pressure of the complicated provisioning and configuration as well as reduces the probability of manually induced configuration errors. (2) Elasticity. VNFs are created, migrated, and destroyed on demand in real time. The reconfigurable hardware resources in pool can rapidly and flexibly offload the corresponding services to the accelerator platform in the dynamic NFV environment. (3) Coordinating with Openstack. The design and implementation of the OpenANFV APIs coordinate with the mechanisms in Openstack to support required virtualized MBs for multiple tenants.
Droid-Sec
Authors: Yuan Zhenlong , Lu Yongqiang , Wang Zhaoguo , Xue Yibo
Published: March 2015

As smartphones and mobile devices are rapidly becoming indispensable for many network users, mobile malware has become a serious threat in the network security and privacy. Especially on the popular Android platform, many malicious apps are hiding in a large number of normal apps, which makes the malware detection more challenging. In this paper, we propose a ML-based method that utilizes more than 200 features extracted from both static analysis and dynamic analysis of Android app for malware detection. The comparison of modeling results demonstrates that the deep learning technique is especially suitable for Android malware detection and can achieve a high level of 96% accuracy with real-world Android application sets.
Rethinking congestion control architecture
Authors: Dong Mo , Li Qingxi , Zarchy Doron , Godfrey Brighten , Schapira Michael
Published: March 2015

After more than two decades of evolution, TCP and its end host based modifications can still suffer from severely degraded performance under real-world challenging network conditions. The reason, as we observe, is due to TCP family's fundamental architectural deficiency, which hardwires packet-level events to control responses and ignores emprical performance. Jumping out of TCP lineage's architectural deficiency, we propose Performance-oriented Congestion Control (PCC), a new congestion control architecture in which each sender controls its sending strategy based on empirically observed performance metrics. We show through preliminary experimental results that PCC achieves consistently high performance under various challenging network conditions.
A time for reliability
Authors: Bischof Zachary S. , Bustamante Fabián E.
Published: March 2015

When a new technology reaches the market, we typically focus on the want or need that it can fulfill. As the technology becomes a commodity and its market matures, reliability often become a key differentiating factor between competing products. We posit that as broadband capacities continue to improve and users migrate to over-the-Internet services, such as on-demand video and voice-over-IP services, we will see this common pattern emerge for broadband services. In this poster, we present the first study of reliability in broadband networks. Using data collected from residential gateways (via FCC/SamKnows), we study the availability and reliability of fixed-line broadband services across the US. Using natural experiments, we look at the impact of increased network downtime on user network demand. We use traditional metrics (e.g. failure rate, MTBF, MTTR) to quantify broadband services, as well as each ISP's configured DNS. Since the impact of a network outage will depend on when it occurred (e.g. time of day), we compare ISP services by the annual average number of bytes lost, based on typical user demand during periods of network downtime.
Aerial wireless localization using target-guided flight route
Authors: Chen Shaofeng , Fang Dingyi , Chen Xiaojiang , Xia Tingting , Jin Meng
Published: March 2015

This poster presents GuideLoc, a highly efficient aerial wireless localization system that uses directional antennas mounted on a mini Multi-rotor Unmanned Aerial Vehicle (UAV), to enable detecting and positioning of targets. Taking advantage of angle and signal strength information of frames transmitted from targets, GuideLoc can directly fly towards the targets with the minimum flight route and time. We implement a prototype of GuideLoc using ArduCopter and evaluate the performance by simulations and experiments. Experimental results show that GuideLoc achieves an average location accuracy of 2.7 meters and reduces flight distance more than 50% compared with other known wireless localization approaches using UAV.
NO production by cNOS and iNOS reflects blood pressure changes in LPS-challenged mice
Authors: Hallemeesch Marcella M. , Janssen Ben J. A. , de Jonge Wouter J. , Soeters Peter B. , Lamers Wouter H. , Deutz Nicolaas E. P.
Published: March 2015

Increased nitric oxide (NO) production is the cause of hypotension and shock during sepsis. In the present experiments, we have measured the contribution of endothelial (e) and inducible (i) nitric oxide synthase (NOS) to systemic NO production in mice under baseline conditions and upon LPS treatment (100 μg/10 g ip LPS). NO synthesis was measured by the rate of conversion of l-[ guanidino-15N2]arginine to l-[ ureido-15N]citrulline, and the contribution of the specific NOS isoforms was evaluated by comparing NO production in eNOS-deficient [(–/–)] and iNOS(–/–) mice with that in wild-type (WT) mice. Under baseline conditions, NO production was similar in WT and iNOS(–/–) mice but lower in eNOS(–/–) mice [WT: 1.2 ± 0.2; iNOS(–/–): 1.2 ± 0.2; eNOS(–/–): 0.6 ± 0.3 nmol · 10 g body wt–1· min–1]. In response to the challenge with LPS (5 h), systemic NO production increased in WT and eNOS(–/–) mice but fell in iNOS(–/–) mice [WT: 2.7 ± 0.3; eNOS(–/–): 2.2 ± 0.6; iNOS(–/–): 0.7 ± 0.1 nmol · 10 g body wt–1· min–1]. After 5 h of LPS treatment, blood pressure had dropped 14 mmHg in WT but not in iNOS(–/–) mice. The present findings provide firm evidence that, upon treatment with bacterial LPS, the increase of NO production is solely dependent on iNOS, whereas that mediated by cNOS is reduced. Furthermore, the data show that the LPS-induced blood pressure response is dependent on iNOS.
Impaired glucose homeostasis in insulin-like growth factor-binding protein-3-transgenic mice
Authors: Silha Josef V. , Gui Yaoting , Murphy Liam J.
Published: March 2015

Glucose homeostasis was examined in male transgenic (Tg) mice that overexpressed the human insulin-like growth factor (IGF)-binding protein (IGFBP)-3 cDNA, driven by either the cytomegalovirus (CMV) or the phosphoglycerate kinase (PGK) promoter. The Tg mice of both lineages demonstrated increased serum levels of human (h) IGFBP-3 and total IGF-I compared with wild-type (Wt) mice. Fasting blood glucose levels were significantly elevated in 8-wk-old CMV-binding protein (CMVBP)-3- and PGK binding protein (PGKBP)-3-Tg mice compared with Wt mice: 6.35 ± 0.22 and 5.22 ± 0.39 vs. 3.99 ± 0.26 mmol/l, respectively. Plasma insulin was significantly elevated only in CMVBP-3-Tg mice. The responses to a glucose challenge were significantly increased in both Tg strains: area under the glucose curve = 1,824 ± 65 and 1,910 ± 115 vs. 1,590 ± 67 mmol · l−1· min for CMVBP-3, PGKBP-3, and Wt mice, respectively. The hypoglycemic effects of insulin and IGF-I were significantly attenuated in Tg mice compared with Wt mice. There were no differences in adipose tissue resistin, retinoid X receptor-α, or peroxisome proliferator-activated receptor-γ mRNA levels between Tg and Wt mice. Uptake of 2-deoxyglucose was reduced in muscle and adipose tissue from Tg mice compared with Wt mice. These data demonstrate that overexpression of hIGFBP-3 results in fasting hyperglycemia, impaired glucose tolerance, and insulin resistance.
Glucocorticoids stimulate humansgk1gene expression by activation of a GRE in its 5′-flanking region
Authors: Itani Omar A. , Liu Kang Z. , Cornish Kristyn L. , Campbell Jason R. , Thomas Christie P.
Published: March 2015

In lung and collecting duct epithelia, glucocorticoid (GC)-stimulated Na+transport is preceded by an increase in the protein kinase sgk1, which in turn regulates the activity of the epithelial Na+channel (ENaC). We investigated the mechanism for GC-regulated human sgk1 expression in lung and renal epithelia. sgk1 mRNA was increased in these epithelia by GCs, and this was inhibited by actinomycin D and superinduced by cycloheximide, consistent with a transcriptional effect that did not require protein synthesis. To understand the basis for transcriptional regulation, the transcription initiation site was mapped and the 5′-flanking region cloned by PCR. A 3-kb fragment of the upstream region was coupled to luciferase and transfected into A549 cells. By deletion analysis, an imperfect GC response element (GRE) was identified that was necessary and sufficient for GC responsiveness. When tested with cell extracts, a specific protein recognized by an anti-GC receptor (GR) antibody bound the GRE in gel mobility shift assays. We conclude that GCs stimulate sgk1 expression in human epithelial cells via activation of a GRE in the 5′-flanking region of sgk1.
Insulin effects on acetate metabolism
Authors: Piloquet H. , Ferchaud-Roucher V. , Duengler F. , Zair Y. , Maugere P. , Krempf M.
Published: March 2015

Acetate metabolism was studied in patients with insulin resistance. To evaluate the interaction between glucose and acetate metabolism, we measured acetate and glucose turnover with a hyperinsulinemic euglycemic clamp (hot clamp) in obese and diabetic patients with insulin resistance ( n = 8) and in a control group with normal insulin sensitivity ( n = 6). At baseline, acetate turnover and plasma concentrations were similar between the two groups (group means: 4.3 ± 0.4 μmol · kg-1 · min-1 and 128.2 ± 11.1 μmol/l). Acetate concentrations decreased in both groups with hyperinsulinemia but were significantly lower in the insulin-resistant group (20% vs. 12%, P < 0.05). After the hot clamp treatment, acetate turnover increased for the two groups and was higher in the group with normal insulin sensitivity: 8.1 ± 0.7 vs. 5.5 ± 0.5 μmol · kg-1 · min-1 ( P < 0.001). No change related to insulin action was observed in either group in the percentage of acetate oxidation. This was ≈70% of overall utilization at baseline and during the clamp. No correlation between glucose and acetate utilization was observed. Our results support the hypothesis that, like glucose metabolism, acetate metabolism is sensitive to insulin.
IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans
Authors: Steensberg Adam , Fischer Christian P. , Keller Charlotte , Møller Kirsten , Pedersen Bente Klarlund
Published: March 2015

The purpose of the present study was to test the hypothesis that a transient increase in plasma IL-6 induces an anti-inflammatory environment in humans. Therefore, young healthy volunteers received a low dose of recombinant human (rh)IL-6 or saline for 3 h. Plasma IL-6 levels during rhIL-6 infusion were ∼140 pg/ml, corresponding to the levels obtained during strenuous exercise. The infusion of rhIL-6 did not induce enhanced levels of the proinflammatory cytokine TNF-α but enhanced the plasma levels of the two anti-inflammatory cytokines IL-1 receptor agonist (IL-1ra) and IL-10 compared with saline infusion. In addition, C-reactive protein increased 3 h post-rhIL-6 infusion and was further elevated 16 h later compared with saline infusion. rhIL-6 induced increased levels of plasma cortisol and, consequently, an increase in circulating neutrophils and a decrease in the lymphocyte number without effects on plasma epinephrine, body temperature, mean arterial pressure, or heart rate. In conclusion, this study demonstrates that physiological concentrations of IL-6 induce an anti-inflammatory rather than an inflammatory response in humans and that IL-6, independently of TNF-α, enhances the levels not only of IL-1ra but also of IL-10. Furthermore, IL-6 induces an increase in cortisol and, consequently, in neutrocytosis and late lymphopenia to the same magnitude and with the same kinetics as during exercise, suggesting that muscle-derived IL-6 has a central role in exercise-induced leukocyte trafficking.
Maternal protein homeostasis and milk protein synthesis during feeding and fasting in humans
Authors: Sunehag Agneta L. , Haymond Morey W.
Published: March 2015

Little is known about amino acid (AA) and protein metabolism in lactating women. We hypothesized: 1) AA sources other than the plasma acid pool provide substrate for milk protein synthesis in humans and 2) if albumin was one such source, then albumin fractional synthesis rate (FSR) is higher in the lactating women. To test these hypotheses, six healthy exclusively breast-feeding women [27 ± 3 yr; body mass index (BMI) 26 ± 2 kg/m2] between 6 wk and 3 mo postpartum and six healthy nonlactating women (28 ± 2 yr; BMI 22 ± 1 kg/m2) were studied two times, in random order, during 22 h fasting or 10 h of continuous feeding with a mixed nutrient drink. Protein metabolism was determined using [1-13C]leucine and [15N2]urea. In both the fed and fasted states, a significant portion of milk protein (20 ± 5 and 31 ± 6%, respectively) was derived from sources other than the plasma free AA pool. A 70% higher ( P < 0.02) FSR of albumin was observed in lactating women during feeding, suggesting that albumin is a likely source of AA for milk protein synthesis. We conclude that plasma free AA contribute only 70–80% of the substrate for milk protein synthesis in humans and that albumin may be a significant source of amino acids for the remainder.
Reduced amino acid availability inhibits muscle protein synthesis and decreases activity of initiation factor eIF2B
Authors: Kobayashi Hisamine , Børsheim Elisabet , Anthony Tracy G. , Traber Daniel L. , Badalamenti John , Kimball Scot R. , Jefferson Leonard S. , Wolfe Robert R.
Published: March 2015

We have examined the effect of a hemodialysis-induced 40% reduction in plasma amino acid concentrations on rates of muscle protein synthesis and breakdown in normal swine. Muscle protein kinetics were measured by tracer methodology using [2H5]phenylalanine and [1-13C]leucine and analysis of femoral arterial and venous samples and tissue biopsies. Net amino acid release by muscle was accelerated during dialysis. Phenylalanine utilization for muscle protein synthesis was reduced from the basal value of 45 ± 8 to 25 ± 6 nmol · min−1· 100 ml leg−1between 30 and 60 min after start of dialysis and was stimulated when amino acids were replaced while dialysis continued. Muscle protein breakdown was unchanged. The signal for changes in synthesis appeared to be changes in plasma amino acid concentrations, as intramuscular concentrations remained constant throughout. The changes in muscle protein synthesis were accompanied by a reduction or stimulation, respectively, in the guanine nucleotide exchange activity of eukaryotic initiation factor (eIF)2B following hypoaminoacidemia vs. amino acid replacement. We conclude that a reduction in plasma amino acid concentrations below the normal basal value signals an inhibition of muscle protein synthesis and that corresponding changes in eIF2B activity suggest a possible role in mediating the response.
Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance
Authors: Kelley David E. , McKolanis Therese M. , Hegazi Refaat A. F. , Kuller Lewis H. , Kalhan Satish C.
Published: March 2015

The current study was undertaken to examine metabolic and body composition correlates of fatty liver in type 2 diabetes mellitus (DM). Eighty-three men and women with type 2 DM [mean body mass index (BMI): 34 ± 0.5 kg/m2] and without clinical or laboratory evidence of liver dysfunction had body composition assessments of fat mass (FM), visceral adipose tissue (VAT), liver and spleen computed tomography (CT) attenuation (ratio of liver to spleen), muscle CT attenuation, and thigh adiposity; these assessments were also performed in 12 lean and 15 obese nondiabetic volunteers. Insulin sensitivity was measured with a euglycemic insulin infusion (40 mU · m–2· min–1) combined with systemic indirect calorimetry to assess glucose and lipid oxidation, and with infusions of [2H2]glucose for assessment of endogenous glucose production. A majority of those with type 2 DM (63%) met CT criteria for fatty liver, compared with 20% of obese and none of the lean nondiabetic volunteers. Fatty liver was most strongly correlated with VAT ( r = –0.57, P < 0.0001) and less strongly but significantly associated with BMI ( r = –0.42, P < 0.001) and FM ( r = –0.37, P < 0.001), but only weakly associated with subcutaneous adiposity ( r = –0.29; P < 0.01). Fatty liver was also correlated with subfascial adiposity of skeletal muscle ( r = –0.44; P < 0.01). Volunteers with type 2 DM and fatty liver were substantially more insulin resistant those with type 2 DM but without fatty liver ( P < 0.001) and had higher levels of plasma free fatty acids ( P < 0.01) and more severe dyslipidemia ( P < 0.01), a pattern observed in both genders. Plasma levels of cytokines were increased in relation to fatty liver ( r = –0.34; P < 0.01). In summary, fatty liver is relatively common in overweight and obese volunteers with type 2 DM and is an aspect of body composition related to severity of insulin resistance, dyslipidemia, and inflammatory markers.
Chemical sympathectomy alters regulation of body weight during prolonged ICV leptin infusion
Authors: Dobbins Robert L. , Szczepaniak Lidia S. , Zhang Weiguo , McGarry J. Denis
Published: March 2015

To assess the importance of the sympathetic nervous system in regulating body weight during prolonged leptin infusion, we evaluated food intake, body weight, and physical activity in conscious, unrestrained rats. Initial studies illustrated that prolonged intracerebroventricular (ICV) infusion of leptin enhanced substrate oxidation so that adipose tissue lipid stores were completely ablated, and muscle triglyceride and liver glycogen stores were depleted. After neonatal chemical sympathectomy, changes in weight and food intake were compared in groups of sympathectomized (SYM) and control (CON) adult animals during ICV infusion of leptin. CON animals lost 60 ± 9 g over 10 days vs. 25 ± 3 g in the SYM animals when food intake was matched between the two groups. Greater weight loss despite similar energy intake points to an important role of the sympathetic nervous system in stimulating energy expenditure during ICV leptin infusion by increasing the resting metabolic rate, since no differences in physical activity were observed between CON and SYM groups. In conclusion, activation of the SNS by leptin increases energy expenditure by augmenting the resting metabolic rate.
Pancreatic vasopressin V1breceptors: characterization in In-R1-G9 cells and localization in human pancreas
Authors: Folny Viviane , Raufaste Danielle , Lukovic Ludovit , Pouzet Brigitte , Rochard Pierrick , Pascal Marc , Serradeil-Le Gal Claudine
Published: March 2015

Vasopressin (AVP) receptors present in In-R1-G9 cells, a hamster glucagon-secreting α-pancreatic cell line, were characterized using SSR-149415, a selective nonpeptide V1breceptor antagonist, and reference AVP compounds. Binding experiments, using [3H]AVP as a ligand, identified a single population of high-affinity binding sites. SSR-149415 competitively inhibited this binding and exhibited nanomolar and stereospecific affinity for these sites. The affinity of various AVP/oxytocin ligands confirmed a V1bbinding profile. In functional studies, AVP was a potent stimulant in inducing intracellular Ca2+increase, glucagon secretion, and cell proliferation. These effects were fully antagonized by SSR-149415 with a nanomolar potency, whereas its diasteroisomer as well as two selective V1aand V2receptor antagonists were much less potent. Additionally, the order of potency of AVP agonists and antagonists was in agreement with V1b-mediated effects. By RT-PCR, we confirmed the presence of V1breceptor mRNA in both In-R1-G9 cells and in human pancreas. The distribution pattern of V1breceptors investigated in human pancreas by immunohistochemistry showed strong labeling in islets of Langerhans, and colocalization studies indicated that this receptor was expressed in α-glucagon, β-insulin, and somatostatin pancreatic cells. Thus, in In-R1-G9 cells, AVP mediates intracellular Ca2+increase, glucagon secretion, and cell proliferation by activating V1breceptors, and these effects are potently antagonized by SSR-149415. Moreover, the presence of V1breceptors also found in human Langerhans islets could suggest hormonal control of AVP in human pancreas.
Intestinal lysine metabolism is driven by the enteral availability of dietary lysine in piglets fed a bolus meal
Authors: Bos Cécile , Stoll Barbara , Fouillet Hélène , Gaudichon Claire , Guan Xinfu , Grusak Michael A. , Reeds Peter J. , Tomé Daniel , Burrin Douglas G.
Published: March 2015

Previous steady-state continuous-feeding studies have shown that the gut mucosa removes substantial amounts of both dietary and systemic amino acids. However, enteral nutrition is often given under non-steady-state conditions as a bolus meal, and this has been shown to influence systemic metabolism. Therefore, our aim was to quantify the relative metabolism of dietary and systemic lysine by the portal-drained viscera (PDV) under non-steady-state conditions after a single bolus meal. Five 28-day-old piglets implanted with arterial, venous, and portal catheters and with an ultrasonic portal flow probe were given an oral bolus feeding of a milk formula containing a trace quantity of intrinsically15N-labeled soy protein and a continuous intravenous infusion of [U-13C]lysine for 8 h. Total lysine use by the PDV was maximal 1 h after the meal (891 μmol·kg–1·h–1) and was predominantly of dietary origin (89%), paralleling the enteral delivery of dietary lysine. Intestinal lysine use returned to a low level after 4 h postprandially and was derived exclusively from the arterial supply until 8 h. Cumulative systemic appearance of dietary lysine reached 44 and 80% of the ingested amount 4 and 8 h after the meal, respectively, whereas the PDV first-pass use of dietary lysine was 55 and 32% of the intake for these two periods, respectively. We conclude that the first-pass utilization rate of dietary lysine by the PDV is directly increased by the enteral lysine availability and that it is higher with a bolus than with continuous oral feeding.
pH is decreased in transplanted rat pancreatic islets
Authors: Carlsson Per-Ola , Nordin Astrid , Palm Fredrik
Published: March 2015

Recent studies of transplanted pancreatic islets have indicated incomplete revascularization. We investigated the pH, in relation to oxygen tension (Po2), in endogenous islets and islets syngeneically transplanted to the renal subcapsular site of nondiabetic and streptozotocin-diabetic recipients. Tissue pH and Po2were measured using microelectrodes. In the endogenous islets, tissue pH was similar to that in arterial blood. In the transplanted islets, tissue pH was 0.11–0.15 pH units lower. No differences in islet graft pH were seen between nondiabetic and diabetic animals, and none if the islet grafts were investigated 1 day or 1 mo posttransplantation. The Po2in the endogenous islets was ∼35 mmHg. Transplanted islets had a markedly lower tissue Po2both 1 day and 1 mo after transplantation. A negative correlation between the tissue Po2and the hydrogen ion concentration was seen in the 1-mo-old islet transplants in diabetic animals. In conclusion, decreased Po2in transplanted islets is associated with a decreased tissue pH, suggesting a shift toward more anaerobic glucose metabolism after transplantation.
Hexokinase II partial knockout impairs exercise-stimulated glucose uptake in oxidative muscles of mice
Authors: Fueger Patrick T. , Heikkinen Sami , Bracy Deanna P. , Malabanan Carlo M. , Pencek R. Richard , Laakso Markku , Wasserman David H.
Published: March 2015

Muscle glucose uptake (MGU) is distributively controlled by three serial steps: delivery of glucose to the muscle membrane, transport across the muscle membrane, and intracellular phosphorylation to glucose 6-phosphate by hexokinase (HK). During states of high glucose fluxes such as moderate exercise, the HK activity is of increased importance, since augmented muscle perfusion increases glucose delivery, and increased GLUT4 at the cell membrane increases glucose transport. Because HK II overexpression augments exercise-stimulated MGU, it was hypothesized that a reduction in HK II activity would impair exercise-stimulated MGU and that the magnitude of this impairment would be greatest in tissues with the largest glucose requirement. To this end, mice with a HK II partial knockout ( HK+/–) were compared with their wild-type control (WT) littermates during either sedentary or moderate exercise periods. Rg, an index of glucose metabolism, was measured using 2-deoxy-[3H]glucose. No differences in glucose metabolism were detected between sedentary groups. The increase in Rgdue to exercise was impaired in the highly oxidative heart and soleus muscles of HK+/–compared with WT mice (7 ± 10 vs. 29 ± 9 and 8 ± 3 vs. 25 ± 7 μmol · 100 g–1· min–1, respectively). However, the increase in Rgdue to exercise was not altered in gastrocnemius and superficial vastus lateralis muscles in HK+/–and WT mice (8 ± 2 vs. 12 ± 3 and 5 ± 2 vs. 8 ± 2 μmol · 100 g–1· min–1, respectively). In conclusion, MGU is impaired by reductions in HK activity during exercise, a physiological condition characterized by high glucose flux. This impairment is critically dependent on the tissue's glucose metabolic rate and correlates with tissue oxidative capacity.
Effects of depletion exercise and light training on muscle glycogen supercompensation in men
Authors: Goforth Harold W. , Laurent Didier , Prusaczyk William K. , Schneider Kevin E. , Petersen Kitt Falk , Shulman Gerald I.
Published: March 2015

Supercompensated muscle glycogen can be achieved by using several carbohydrate (CHO)-loading protocols. This study compared the effectiveness of two “modified” CHO-loading protocols. Additionally, we determined the effect of light cycle training on muscle glycogen. Subjects completed a depletion (D, n = 15) or nondepletion (ND, n = 10) CHO-loading protocol. After a 2-day adaptation period in a metabolic ward, the D group performed a 120-min cycle exercise at 65% peak oxygen uptake (V̇o2 peak) followed by 1-min sprints at 120% V̇o2 peakto exhaustion. The ND group performed only 20-min cycle exercise at 65% V̇o2 peak. For the next 6 days, both groups ate the same high-CHO diets and performed 20-min daily cycle exercise at 65% V̇o2 peakfollowed by a CHO beverage (105 g of CHO). Muscle glycogen concentrations of the vastus lateralis were measured daily with13C magnetic resonance spectroscopy. On the morning of day 5, muscle glycogen concentrations had increased 1.45 (D) and 1.24 (ND) times baseline ( P < 0.001) but did not differ significantly between groups. However, on day 7, muscle glycogen of the D group was significantly greater ( p < 0.01) than that of the ND group (130 ± 7 vs. 104 ± 5 mmol/l). Daily cycle exercise decreased muscle glycogen by 10 ± 2 (D) and 14 ± 5 mmol/l (ND), but muscle glycogen was equal to or greater than preexercise values 24 h later. In conclusion, a CHO-loading protocol that begins with a glycogen-depleting exercise results in significantly greater muscle glycogen that persists longer than a CHO-loading protocol using only an exercise taper. Daily exercise at 65% V̇o2 peakfor 20 min can be performed throughout the CHO-loading protocol without negatively affecting muscle glycogen supercompensation.