bluuebunny/crossref_metadata_2025 huggingface dataset:
PuDianNao
Authors: Liu Daofu , Chen Tianshi , Liu Shaoli , Zhou Jinhong , Zhou Shengyuan , Teman Olivier , Feng Xiaobing , Zhou Xuehai , Chen Yunji
Published: May 2015

Machine Learning (ML) techniques are pervasive tools in various emerging commercial applications, but have to be accommodated by powerful computer systems to process very large data. Although general-purpose CPUs and GPUs have provided straightforward solutions, their energy-efficiencies are limited due to their excessive supports for flexibility. Hardware accelerators may achieve better energy-efficiencies, but each accelerator often accommodates only a single ML technique (family). According to the famous No-Free-Lunch theorem in the ML domain, however, an ML technique performs well on a dataset may perform poorly on another dataset, which implies that such accelerator may sometimes lead to poor learning accuracy. Even if regardless of the learning accuracy, such accelerator can still become inapplicable simply because the concrete ML task is altered, or the user chooses another ML technique.

In this study, we present an ML accelerator called PuDianNao, which accommodates seven representative ML techniques, including k-means, k-nearest neighbors, naive bayes, support vector machine, linear regression, classification tree, and deep neural network. Benefited from our thorough analysis on computational primitives and locality properties of different ML techniques, PuDianNao can perform up to 1056 GOP/s (e.g., additions and multiplications) in an area of 3.51 mm^2, and consumes 596 mW only. Compared with the NVIDIA K20M GPU (28nm process), PuDianNao (65nm process) is 1.20x faster, and can reduce the energy by 128.41x.
Asynchronized Concurrency
Authors: David Tudor , Guerraoui Rachid , Trigonakis Vasileios
Published: May 2015

We introduce "asynchronized concurrency (ASCY)," a paradigm consisting of four complementary programming patterns. ASCY calls for the design of concurrent search data structures (CSDSs) to resemble that of their sequential counterparts. We argue that ASCY leads to implementations which are portably scalable: they scale across different types of hardware platforms, including single and multi-socket ones, for various classes of workloads, such as read-only and read-write, and according to different performance metrics, including throughput, latency, and energy. We substantiate our thesis through the most exhaustive evaluation of CSDSs to date, involving 6 platforms, 22 state-of-the-art CSDS algorithms, 10 re-engineered state-of-the-art CSDS algorithms following the ASCY patterns, and 2 new CSDS algorithms designed with ASCY in mind. We observe up to 30% improvements in throughput in the re-engineered algorithms, while our new algorithms out-perform the state-of-the-art alternatives.
Automated OS-level Device Runtime Power Management
Authors: Xu Chao , Lin Felix Xiaozhu , Wang Yuyang , Zhong Lin
Published: May 2015

Non-CPU devices on a modern system-on-a-chip (SoC), ranging from accelerators to I/O controllers, account for a significant portion of the chip area. It is therefore vital for system energy efficiency that idle devices can enter a low-power state while still meeting the performance expectation. This is called device runtime Power Management (PM) for which individual device drivers in commodity OSes are held responsible today. Based on the observations of existing drivers and their evolution, we consider it harmful to rely on drivers for device runtime PM. This paper identifies three pieces of information as essential to device runtime PM, and shows that they can be obtained without involving drivers, either by using a software-only approach, or more efficiently, by adding one register bit to each device. We thus suggest a structural change to the current Linux runtime PM framework, replacing the PM code in all applicable drivers with a single kernel module called the central PM agent. Experimental evaluations show that the central PM agent is just as effective as hand-tuned driver PM code. The paper also presents a tool called PowerAdvisor that simplifies driver PM efforts under the current Linux runtime PM framework. PowerAdvisor analyzes execution traces and suggests where to insert PM calls in driver source code. Despite being a best-effort tool, PowerAdvisor not only reproduces hand-tuned PM code from stock drivers, but also correctly suggests PM code never known before. Overall, our experience shows that it is promising to ultimately free driver developers from manual PM.
NumaGiC
Authors: Gidra Lokesh , Thomas Gaël , Sopena Julien , Shapiro Marc , Nguyen Nhan
Published: May 2015

On contemporary cache-coherent Non-Uniform Memory Access (ccNUMA) architectures, applications with a large memory footprint suffer from the cost of the garbage collector (GC), because, as the GC scans the reference graph, it makes many remote memory accesses, saturating the interconnect between memory nodes. We address this problem with NumaGiC, a GC with a mostly-distributed design. In order to maximise memory access locality during collection, a GC thread avoids accessing a different memory node, instead notifying a remote GC thread with a message; nonetheless, NumaGiC avoids the drawbacks of a pure distributed design, which tends to decrease parallelism. We compare NumaGiC with Parallel Scavenge and NAPS on two different ccNUMA architectures running on the Hotspot Java Virtual Machine of OpenJDK 7. On Spark and Neo4j, two industry-strength analytics applications, with heap sizes ranging from 160GB to 350GB, and on SPECjbb2013 and SPECjbb2005, ourgc improves overall performance by up to 45% over NAPS (up to 94% over Parallel Scavenge), and increases the performance of the collector itself by up to 3.6x over NAPS (up to 5.4x over Parallel Scavenge).
PolyMage
Authors: Mullapudi Ravi Teja , Vasista Vinay , Bondhugula Uday
Published: May 2015

This paper presents the design and implementation of PolyMage, a domain-specific language and compiler for image processing pipelines. An image processing pipeline can be viewed as a graph of interconnected stages which process images successively. Each stage typically performs one of point-wise, stencil, reduction or data-dependent operations on image pixels. Individual stages in a pipeline typically exhibit abundant data parallelism that can be exploited with relative ease. However, the stages also require high memory bandwidth preventing effective utilization of parallelism available on modern architectures. For applications that demand high performance, the traditional options are to use optimized libraries like OpenCV or to optimize manually. While using libraries precludes optimization across library routines, manual optimization accounting for both parallelism and locality is very tedious.

The focus of our system, PolyMage, is on automatically generating high-performance implementations of image processing pipelines expressed in a high-level declarative language. Our optimization approach primarily relies on the transformation and code generation capabilities of the polyhedral compiler framework. To the best of our knowledge, this is the first model-driven compiler for image processing pipelines that performs complex fusion, tiling, and storage optimization automatically. Experimental results on a modern multicore system show that the performance achieved by our automatic approach is up to 1.81x better than that achieved through manual tuning in Halide, a state-of-the-art language and compiler for image processing pipelines. For a camera raw image processing pipeline, our performance is comparable to that of a hand-tuned implementation.
SPECS
Authors: Hicks Matthew , Sturton Cynthia , King Samuel T. , Smith Jonathan M.
Published: May 2015

Processor implementation errata remain a problem, and worse, a subset of these bugs are security-critical. We classified 7 years of errata from recent commercial processors to understand the magnitude and severity of this problem, and found that of 301 errata analyzed, 28 are security-critical. We propose the SECURITY-CRITICAL PROCESSOR ER- RATA CATCHING SYSTEM (SPECS) as a low-overhead solution to this problem. SPECS employs a dynamic verification strategy that is made lightweight by limiting protection to only security-critical processor state. As a proof-of- concept, we implement a hardware prototype of SPECS in an open source processor. Using this prototype, we evaluate SPECS against a set of 14 bugs inspired by the types of security-critical errata we discovered in the classification phase. The evaluation shows that SPECS is 86% effective as a defense when deployed using only ISA-level state; incurs less than 5% area and power overhead; and has no software run-time overhead.
iThreads
Authors: Bhatotia Pramod , Fonseca Pedro , Acar Umut A. , Brandenburg Björn B. , Rodrigues Rodrigo
Published: May 2015

Incremental computation strives for efficient successive runs of applications by re-executing only those parts of the computation that are affected by a given input change instead of recomputing everything from scratch. To realize these benefits automatically, we describe iThreads, a threading library for parallel incremental computation. iThreads supports unmodified shared-memory multithreaded programs: it can be used as a replacement for pthreads by a simple exchange of dynamically linked libraries, without even recompiling the application code. To enable such an interface, we designed algorithms and an implementation to operate at the compiled binary code level by leveraging MMU-assisted memory access tracking and process-based thread isolation. Our evaluation on a multicore platform using applications from the PARSEC and Phoenix benchmarks and two case-studies shows significant performance gains.
A Probabilistic Graphical Model-based Approach for Minimizing Energy Under Performance Constraints
Authors: Mishra Nikita , Zhang Huazhe , Lafferty John D. , Hoffmann Henry
Published: May 2015

In many deployments, computer systems are underutilized -- meaning that applications have performance requirements that demand less than full system capacity. Ideally, we would take advantage of this under-utilization by allocating system resources so that the performance requirements are met and energy is minimized. This optimization problem is complicated by the fact that the performance and power consumption of various system configurations are often application -- or even input -- dependent. Thus, practically, minimizing energy for a performance constraint requires fast, accurate estimations of application-dependent performance and power tradeoffs. This paper investigates machine learning techniques that enable energy savings by learning Pareto-optimal power and performance tradeoffs. Specifically, we propose LEO, a probabilistic graphical model-based learning system that provides accurate online estimates of an application's power and performance as a function of system configuration. We compare LEO to (1) offline learning, (2) online learning, (3) a heuristic approach, and (4) the true optimal solution. We find that LEO produces the most accurate estimates and near optimal energy savings.
Architectural Support for Cyber-Physical Systems
Authors: Lee Edward A.
Published: May 2015

Cyber-physical systems are integrations of computation, communication networks, and physical dynamics. Although time plays a central role in the physical world, all widely used software abstractions lack temporal semantics. The notion of correct execution of a program written in every widely-used programming language today does not depend on the temporal behavior of the program. But temporal behavior matters in almost all systems, and most particularly in cyber-physical systems. In this talk, I will argue that time can and must become part of the semantics of programs for a large class of applications. To illustrate that this is both practical and useful, we will describe a recent effort at Berkeley in the design and implementation of timing-centric software systems. Specifically, I will describe PRET machines, which redefine the instruction-set architecture (ISA) of a microprocessor to embrace temporal semantics. Such machines can be used in high-confidence and safety-critical systems, in energy-constrained systems, in mixed-criticality systems, and as a Real-Time Unit (RTU) that cooperates with a general-purpose processor to provide real-time services, in a manner similar to how a GPU provides graphics services.
More is Less, Less is More
Authors: Pang Jun , Dwyer Chris , Lebeck Alvin R.
Published: May 2015

Molecular-scale Network-on-Chip (mNoC) crossbars use quantum dot LEDs as an on-chip light source, and chromophores to provide optical signal filtering for receivers. An mNoC reduces power consumption or enables scaling to larger crossbars for a reduced energy budget compared to current nanophotonic NoC crossbars. Since communication latency is reduced by using a high-radix crossbar, minimizing power consumption becomes a primary design target. Conventional Single Writer Multiple Reader (SWMR) photonic crossbar designs broadcast all packets, and incur the commensurate required power, even if only two nodes are communicating.

This paper introduces power topologies, enabled by unique capabilities of mNoC technology, to reduce overall interconnect power consumption. A power topology corresponds to the logical connectivity provided by a given power mode. Broadcast is one power mode and it consumes the maximum power. Additional power modes consume less power but allow a source to communicate with only a statically defined, potentially non-contiguous, subset of nodes. Overall interconnect power is reduced if the more frequently communicating nodes use modes that consume less power, while less frequently communicating nodes use modes that consume more power. We also investigate thread mapping techniques to fully exploit power topologies. We explore various mNoC power topologies with one, two and four power modes for a radix-256 SWMR mNoC crossbar. Our results show that the combination of power topologies and intelligent thread mapping can reduce total mNoC power by up to 51% on average for a set of 12 SPLASH benchmarks. Furthermore performance is 10% better than conventional resonator-based photonic NoCs and energy is reduced by 72%.
Protecting Data on Smartphones and Tablets from Memory Attacks
Authors: Colp Patrick , Zhang Jiawen , Gleeson James , Suneja Sahil , de Lara Eyal , Raj Himanshu , Saroiu Stefan , Wolman Alec
Published: May 2015

Smartphones and tablets are easily lost or stolen. This makes them susceptible to an inexpensive class of memory attacks, such as cold-boot attacks, using a bus monitor to observe the memory bus, and DMA attacks. This paper describes Sentry, a system that allows applications and OS components to store their code and data on the System-on-Chip (SoC) rather than in DRAM. We use ARM-specific mechanisms originally designed for embedded systems, but still present in today's mobile devices, to protect applications and OS subsystems from memory attacks.
Nested Kernel
Authors: Dautenhahn Nathan , Kasampalis Theodoros , Dietz Will , Criswell John , Adve Vikram
Published: May 2015

Monolithic operating system designs undermine the security of computing systems by allowing single exploits anywhere in the kernel to enjoy full supervisor privilege. The nested kernel operating system architecture addresses this problem by "nesting" a small isolated kernel within a traditional monolithic kernel. The "nested kernel" interposes on all updates to virtual memory translations to assert protections on physical memory, thus significantly reducing the trusted computing base for memory access control enforcement. We incorporated the nested kernel architecture into FreeBSD on x86-64 hardware while allowing the entire operating system, including untrusted components, to operate at the highest hardware privilege level by write-protecting MMU translations and de-privileging the untrusted part of the kernel. Our implementation inherently enforces kernel code integrity while still allowing dynamically loaded kernel modules, thus defending against code injection attacks. We also demonstrate that the nested kernel architecture allows kernel developers to isolate memory in ways not possible in monolithic kernels by introducing write-mediation and write-logging services to protect critical system data structures. Performance of the nested kernel prototype shows modest overheads: <1% average for Apache and 2.7% for kernel compile. Overall, our results and experience show that the nested kernel design can be retrofitted to existing monolithic kernels, providing important security benefits.
DEUCE
Authors: Young Vinson , Nair Prashant J. , Qureshi Moinuddin K.
Published: May 2015

Phase Change Memory (PCM) is an emerging Non Volatile Memory (NVM) technology that has the potential to provide scalable high-density memory systems. While the non-volatility of PCM is a desirable property in order to save leakage power, it also has the undesirable effect of making PCM main memories susceptible to newer modes of security vulnerabilities, for example, accessibility to sensitive data if a PCM DIMM gets stolen. PCM memories can be made secure by encrypting the data. Unfortunately, such encryption comes with a significant overhead in terms of bits written to PCM memory, causing half of the bits in the line to change on every write, even if the actual number of bits being written to memory is small. Our studies show that a typical writeback modifies, on average, only 12% of the bits in the cacheline. Thus, encryption causes almost a 4x increase in the number of bits written to PCM memories. Such extraneous bit writes cause significant increase in write power, reduction in write endurance, and reduction in write bandwidth. To provide the benefit of secure memory in a write efficient manner this paper proposes Dual Counter Encryption (DEUCE). DEUCE is based on the observation that a typical writeback only changes a few words, so DEUCE reencrypts only the words that have changed. We show that DEUCE reduces the number of modified bits per writeback for a secure memory from 50% to 24%, which improves performance by 27% and increases lifetime by 2x.
Asymmetric Memory Fences
Authors: Duan Yuelu , Honarmand Nima , Torrellas Josep
Published: May 2015

There have been several recent efforts to improve the performance of fences. The most aggressive designs allow post-fence accesses to retire and complete before the fence completes. Unfortunately, such designs present implementation difficulties due to their reliance on global state and structures.

This paper's goal is to optimize both the performance and the implementability of fences. We start-off with a design like the most aggressive ones but without the global state. We call it Weak Fence or wF. Since the concurrent execution of multiple wFs can deadlock, we combine wFs with a conventional fence (i.e., Strong Fence or sF) for the less performance-critical thread(s). We call the result an Asymmetric fence group. We also propose a taxonomy of Asymmetric fence groups under TSO. Compared to past aggressive fences, Asymmetric fence groups both are substantially easier to implement and have higher average performance. The two main designs presented (WS+ and W+) speed-up workloads under TSO by an average of 13% and 21%, respectively, over conventional fences.
Targeted Automatic Integer Overflow Discovery Using Goal-Directed Conditional Branch Enforcement
Authors: Sidiroglou-Douskos Stelios , Lahtinen Eric , Rittenhouse Nathan , Piselli Paolo , Long Fan , Kim Deokhwan , Rinard Martin
Published: May 2015

We present a new technique and system, DIODE, for auto- matically generating inputs that trigger overflows at memory allocation sites. DIODE is designed to identify relevant sanity checks that inputs must satisfy to trigger overflows at target memory allocation sites, then generate inputs that satisfy these sanity checks to successfully trigger the overflow. DIODE works with off-the-shelf, production x86 binaries. Our results show that, for our benchmark set of applications, and for every target memory allocation site exercised by our seed inputs (which the applications process correctly with no overflows), either 1) DIODE is able to generate an input that triggers an overflow at that site or 2) there is no input that would trigger an overflow for the observed target expression at that site.
VARAN the Unbelievable
Authors: Hosek Petr , Cadar Cristian
Published: May 2015

With the widespread availability of multi-core processors, running multiple diversified variants or several different versions of an application in parallel is becoming a viable approach for increasing the reliability and security of software systems. The key component of such N-version execution (NVX) systems is a runtime monitor that enables the execution of multiple versions in parallel. Unfortunately, existing monitors impose either a large performance overhead or rely on intrusive kernel-level changes. Moreover, none of the existing solutions scales well with the number of versions, since the runtime monitor acts as a performance bottleneck.

In this paper, we introduce Varan, an NVX framework that combines selective binary rewriting with a novel event-streaming architecture to significantly reduce performance overhead and scale well with the number of versions, without relying on intrusive kernel modifications.

Our evaluation shows that Varan can run NVX systems based on popular C10k network servers with only a modest performance overhead, and can be effectively used to increase software reliability using techniques such as transparent failover, live sanitization and multi-revision execution.
Itaconic Acid: The Surprising Role of an Industrial Compound as a Mammalian Antimicrobial Metabolite
Authors: Cordes Thekla , Michelucci Alessandro , Hiller Karsten
Published: May 2015

Itaconic acid is well known as a precursor for polymer synthesis and has been involved in industrial processes for decades. In a recent surprising discovery, itaconic acid was found to play a role as an immune-supportive metabolite in mammalian immune cells, where it is synthesized as an antimicrobial compound from the citric acid cycle intermediate cis-aconitic acid. Although the immune-responsive gene 1 protein (IRG1) has been associated to immune response without a mechanistic function, the critical link to itaconic acid production through an enzymatic function of this protein was only recently revealed. In this review, we highlight the history of itaconic acid as an industrial and antimicrobial compound, starting with its biotechnological synthesis and ending with its antimicrobial function in mammalian immune cells.
Regulation of Selenium Metabolism and Transport
Authors: Burk Raymond F. , Hill Kristina E.
Published: May 2015

Selenium is regulated in the body to maintain vital selenoproteins and to avoid toxicity. When selenium is limiting, cells utilize it to synthesize the selenoproteins most important to them, creating a selenoprotein hierarchy in the cell. The liver is the central organ for selenium regulation and produces excretory selenium forms to regulate whole-body selenium. It responds to selenium deficiency by curtailing excretion and secreting selenoprotein P (Sepp1) into the plasma at the expense of its intracellular selenoproteins. Plasma Sepp1 is distributed to tissues in relation to their expression of the Sepp1 receptor apolipoprotein E receptor-2, creating a tissue selenium hierarchy. N-terminal Sepp1 forms are taken up in the renal proximal tubule by another receptor, megalin. Thus, the regulated whole-body pool of selenium is shifted to needy cells and then to vital selenoproteins in them to supply selenium where it is needed, creating a whole-body selenoprotein hierarchy.
CoQ10 Function and Role in Heart Failure and Ischemic Heart Disease
Authors: Ayer Anita , Macdonald Peter , Stocker Roland
Published: May 2015

Coenzyme Q (CoQ) is an essential lipid of cells present in all cellular compartments. The functions of CoQ in mitochondrial respiration and as an antioxidant are established, although the lipid likely has additional, presently unknown, roles. While the therapeutic utility of CoQ10 supplements is recognized in the rare cases of primary CoQ10 deficiencies, a potential role for CoQ10 supplements in cardiovascular disease, particularly heart failure, has also been studied for over 40 years. This review summarizes our current knowledge in these areas derived from animal studies and human trials. Current evidence for a benefit of CoQ10 supplements in diseases other than primary CoQ10 deficiencies is insufficient.
Use of Urine Biomarkers to Assess Sodium Intake: Challenges and Opportunities
Authors: Cogswell Mary E. , Maalouf Joyce , Elliott Paul , Loria Catherine M. , Patel Sheena , Bowman Barbara A.
Published: May 2015

This article summarizes current data and approaches to assess sodium intake in individuals and populations. A review of the literature on sodium excretion and intake estimation supports the continued use of 24-h urine collections for assessing population and individual sodium intake. Since 2000, 29 studies used urine biomarkers to estimate population sodium intake, primarily among adults. More than half used 24-h urine; the rest used a spot/casual, overnight, or 12-h specimen. Associations between individual sodium intake and health outcomes were investigated in 13 prospective cohort studies published since 2000. Only three included an indicator of long-term individual sodium intake, i.e., multiple 24-h urine specimens collected several days apart. Although not insurmountable, logistic challenges of 24-h urine collection remain a barrier for research on the relationship of sodium intake and chronic disease. Newer approaches, including modeling based on shorter collections, offer promise for estimating population sodium intake in some groups.
Glycemic Variability: Assessing Glycemia Differently and the Implications for Dietary Management of Diabetes
Authors: Tay Jeannie , Thompson Campbell H. , Brinkworth Grant D.
Published: May 2015

The primary therapeutic target for diabetes management is the achievement of good glycemic control, of which glycated hemoglobin (HbA1c) remains the standard clinical marker. However, glycemic variability (GV; the amplitude, frequency, and duration of glycemic fluctuations around mean blood glucose) is an emerging target for blood glucose control. A growing body of evidence supports GV as an independent risk factor for diabetes complications. Several techniques have been developed to assess and quantify intraday and interday GV. Additionally, GV can be influenced by several nutritional factors, including carbohydrate quality, quantity; and distribution; protein intake; and fiber intake. These factors have important implications for clinical nutrition practice and for optimizing blood glucose control for diabetes management. This review discusses the available evidence for GV as a marker of glycemic control and risk factor for diabetes complications. GV quantification techniques and the influence of nutritional considerations for diabetes management are also discussed.
Tissue-nonspecific alkaline phosphatase as a target of sFRP2 in cardiac fibroblasts
Authors: Martin Sean , Lin Huey , Ejimadu Chukwuemeka , Lee Techung
Published: May 2015

Recent studies of myocardial infarction in secreted Frizzled-related protein 2 (sFRP2) knockout mice and our hamster heart failure therapy based on sFRP2 blockade have established sFRP2 as a key profibrotic cytokine in the heart. The failing hamster heart is marked by prominent fibrosis and calcification with elevated expression of sFRP2. Noting the involvement of tissue-nonspecific alkaline phosphatase (TNAP) in bone mineralization and vascular calcification, we determined whether sFRP2 might be an upstream regulator of TNAP. Biochemical assays revealed an approximately twofold increase in the activity of TNAP and elevated levels of inorganic phosphate (Pi) in the failing heart compared with the normal heart. Neither was this change detected in the liver or hamstring muscle nor was it associated with systemic hyperphosphatemia. TNAP was readily cloned from the hamster heart and upon overexpression increased the level of extracellular but not intracellular Pi, which is consistent with the cell surface location of the ectoenzyme. In line with the previous demonstration that sFRP2 blockade attenuated fibrosis, we show here that the therapy downregulated TNAP. This in vivo finding is corroborated by the in vitro study showing that cultured cardiac fibroblasts treated with recombinant sFRP2 protein exhibited progressive increase in the expression and activity of TNAP, which was completely abrogated by cycloheximide or tunicamycin. Induction of TNAP by sFRP2 is restricted to cardiac fibroblasts among the multiple cell types examined, and was not observed with sFRP4. The current work indicates that sFRP2 may promote cardiac fibrocalcification through coordinate activation of tolloid-like metalloproteinases and TNAP.
Femoral lipectomy increases postprandial lipemia in women
Authors: Hernandez Teri L. , Bessesen Daniel H. , Cox-York Kimberly A. , Erickson Christopher B. , Law Christopher K. , Anderson Molly K. , Wang Hong , Jackman Matthew R. , Van Pelt Rachael E.
Published: May 2015

Femoral subcutaneous adipose tissue (SAT) appears to be cardioprotective compared with abdominal SAT, possibly through better triglyceride (TG) sequestration. We hypothesized that removal of femoral SAT would increase postprandial TG through a reduction in dietary fatty acid (FA) storage. Normal-weight (means ± SD; BMI 23.9 ± 2.6 kg/m2) women ( n = 29; age 45 ± 6 yr) were randomized to femoral lipectomy (LIPO) or control (CON) and followed for 1 yr. Regional adiposity was measured by DEXA and CT. A liquid meal labeled with [14C]oleic acid was used to trace the appearance of dietary FA in plasma (6-h postprandial TG), breath (24-h oxidation), and SAT (24-h [14C]TG storage). Fasting LPL activity was measured in abdominal and femoral SAT. DEXA leg fat mass was reduced after LIPO vs. CON (Δ−1.4 ± 0.7 vs. 0.1 ± 0.5 kg, P < 0.001) and remained reduced at 1 yr (−1.1 ± 1.4 vs. −0.2 ± 0.5 kg, P < 0.05), as did CT thigh subcutaneous fat area (−39.6 ± 36.6 vs. 4.7 ± 14.6 cm2, P < 0.05); DEXA trunk fat mass and CT visceral fat area were unchanged. Postprandial TG increased (5.9 ± 7.7 vs. −0.6 ± 5.3 × 103mg/dl, P < 0.05) and femoral SAT LPL activity decreased (−21.9 ± 22.3 vs. 10.5 ± 26.5 nmol·min−1·g−1, P < 0.05) 1 yr following LIPO vs. CON. There were no group differences in14C-labeled TG appearing in abdominal and femoral SAT or elsewhere. In conclusion, femoral fat remained reduced 1 yr following lipectomy and was accompanied by increased postprandial TG and reduced femoral SAT LPL activity. There were no changes in storage of meal-derived FA or visceral fat. Our data support a protective role for femoral adiposity on circulating TG independent of dietary FA storage and visceral adiposity.
Uterine artery dysfunction in pregnant ACE2 knockout mice is associated with placental hypoxia and reduced umbilical blood flow velocity
Authors: Yamaleyeva Liliya M. , Pulgar Victor M. , Lindsey Sarah H. , Yamane Larissa , Varagic Jasmina , McGee Carolynne , daSilva Mauro , Lopes Bonfa Paula , Gurley Susan B. , Brosnihan K. Bridget
Published: May 2015

Angiotensin-converting enzyme 2 (ACE2) knockout is associated with reduced fetal weight at late gestation; however, whether uteroplacental vascular and/or hemodynamic disturbances underlie this growth-restricted phenotype is unknown. Uterine artery reactivity and flow velocities, umbilical flow velocities, trophoblast invasion, and placental hypoxia were determined in ACE2 knockout (KO) and C57Bl/6 wild-type (WT) mice at day 14 of gestation. Although systolic blood pressure was higher in pregnant ACE2 KO vs. WT mice (102.3 ± 5.1 vs. 85.1 ± 1.9 mmHg, n = 5–6), the magnitude of difference was similar to that observed in nonpregnant ACE2 KO vs. WT mice. Maternal urinary protein excretion, serum creatinine, and kidney or heart weights were not different in ACE2 KO vs. WT. Fetal weight and pup-to-placental weight ratio were lower in ACE2 KO vs. WT mice. A higher sensitivity to Ang II [pD2 8.64 ± 0.04 vs. 8.5 ± 0.03 (−log EC50)] and greater maximal contraction to phenylephrine (169.0 ± 9.0 vs. 139.0 ± 7.0% KMAX), were associated with lower immunostaining for Ang II receptor 2 and fibrinoid content of the uterine artery in ACE2 KO mice. Uterine artery flow velocities and trophoblast invasion were similar between study groups. In contrast, umbilical artery peak systolic velocities (60.2 ± 4.5 vs. 75.1 ± 4.5 mm/s) and the resistance index measured using VEVO 2100 ultrasound were lower in the ACE2 KO vs. WT mice. Immunostaining for pimonidazole, a marker of hypoxia, and hypoxia-inducible factor-2α were higher in the trophospongium and placental labyrinth of the ACE2 KO vs. WT. In summary, placental hypoxia and uterine artery dysfunction develop before major growth of the fetus occurs and may explain the fetal growth restricted phenotype.
Deceleration of liver regeneration by knockdown of augmenter of liver regeneration gene is associated with impairment of mitochondrial DNA synthesis in mice
Authors: Han Li-hong , Dong Ling-yue , Yu Hao , Sun Guang-yong , Wu Yuan , Gao Jian , Thasler Wolfgang , An Wei
Published: May 2015

Hepatic stimulator substance, also known as augmenter of liver regeneration (ALR), is a novel hepatic mitogen that stimulates liver regeneration after partial hepatectomy (PH). Recent work has indicated that a lack of ALR expression inhibited liver regeneration in rats, and the mechanism seems to be related to increased cell apoptosis. The mitochondria play an important role during liver regeneration. Adequate ATP supply, which is largely dependent on effective mitochondrial biogenesis, is essential for progress of liver regeneration. However, ALR gene expression during liver regeneration, particularly its function with mitochondrial DNA synthesis, remains poorly understood. In this study, ALR expression in hepatocytes of mice was suppressed with ALR short-hairpin RNA interference or ALR deletion (knockout, KO). The ALR-defective mice underwent PH, and the liver was allowed to regenerate for 1 wk. Analysis of liver growth and its correlation with mitochondrial biogenesis showed that both ALR mRNA and protein levels increased robustly in control mice with a maximum at days 3 and 4 post-PH. However, ALR knockdown inhibited hepatic DNA synthesis and decelerated liver regeneration after PH. Furthermore, both in the ALR-knockdown and ALR-KO mice, expression of mitochondrial transcription factor A and peroxisome proliferator-activated receptor-γ coactivator-1α were reduced, resulting in impaired mitochondrial biogenesis. In conclusion, ALR is apparently required to ensure appropriate liver regeneration following PH in mice, and deletion of the ALR gene may delay liver regeneration in part due to impaired mitochondrial biogenesis.
Pendrin gene ablation alters ENaC subcellular distribution and open probability
Authors: Pech Vladimir , Wall Susan M. , Nanami Masayoshi , Bao Hui-Fang , Kim Young Hee , Lazo-Fernandez Yoskaly , Yue Qiang , Pham Truyen D. , Eaton Douglas C. , Verlander Jill W.
Published: May 2015

The present study explored whether the intercalated cell Cl−/HCO3−exchanger pendrin modulates epithelial Na+channel (ENaC) function by changing channel open probability and/or channel density. To do so, we measured ENaC subunit subcellular distribution by immunohistochemistry, single channel recordings in split open cortical collecting ducts (CCDs), as well as transepithelial voltage and Na+absorption in CCDs from aldosterone-treated wild-type and pendrin-null mice. Because pendrin gene ablation reduced 70-kDa more than 85-kDa γ-ENaC band density, we asked if pendrin gene ablation interferes with ENaC cleavage. We observed that ENaC-cleaving protease application (trypsin) increased the lumen-negative transepithelial voltage in pendrin-null mice but not in wild-type mice, which raised the possibility that pendrin gene ablation blunts ENaC cleavage, thereby reducing open probability. In mice harboring wild-type ENaC, pendrin gene ablation reduced ENaC-mediated Na+absorption by reducing channel open probability as well as by reducing channel density through changes in subunit total protein abundance and subcellular distribution. Further experiments used mice with blunted ENaC endocytosis and degradation (Liddle's syndrome) to explore the significance of pendrin-dependent changes in ENaC open probability. In mouse models of Liddle's syndrome, pendrin gene ablation did not change ENaC subunit total protein abundance, subcellular distribution, or channel density, but markedly reduced channel open probability. We conclude that in mice harboring wild-type ENaC, pendrin modulates ENaC function through changes in subunit abundance, subcellular distribution, and channel open probability. In a mouse model of Liddle's syndrome, however, pendrin gene ablation reduces channel activity mainly through changes in open probability.
Modulating exercise-induced hormesis: Does less equal more?
Authors: Peake Jonathan M. , Markworth James F. , Nosaka Kazunori , Raastad Truls , Wadley Glenn D. , Coffey Vernon G.
Published: May 2015

Hormesis encompasses the notion that low levels of stress stimulate or upregulate existing cellular and molecular pathways that improve the capacity of cells and organisms to withstand greater stress. This notion underlies much of what we know about how exercise conditions the body and induces long-term adaptations. During exercise, the body is exposed to various forms of stress, including thermal, metabolic, hypoxic, oxidative, and mechanical stress. These stressors activate biochemical messengers, which in turn activate various signaling pathways that regulate gene expression and adaptive responses. Historically, antioxidant supplements, nonsteroidal anti-inflammatory drugs, and cryotherapy have been favored to attenuate or counteract exercise-induced oxidative stress and inflammation. However, reactive oxygen species and inflammatory mediators are key signaling molecules in muscle, and such strategies may mitigate adaptations to exercise. Conversely, withholding dietary carbohydrate and restricting muscle blood flow during exercise may augment adaptations to exercise. In this review article, we combine, integrate, and apply knowledge about the fundamental mechanisms of exercise adaptation. We also critically evaluate the rationale for using interventions that target these mechanisms under the overarching concept of hormesis. There is currently insufficient evidence to establish whether these treatments exert dose-dependent effects on muscle adaptation. However, there appears to be some dissociation between the biochemical/molecular effects and functional/performance outcomes of some of these treatments. Although several of these treatments influence common kinases, transcription factors, and proteins, it remains to be determined if these interventions complement or negate each other, and whether such effects are strong enough to influence adaptations to exercise.
Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment
Authors: Guo Qian , Guo Jiabin , Yang Rong , Peng Hui , Zhao Jun , Li Li , Peng Shuangqing
Published: May 2015

The clinical application of doxorubicin (DOX) is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D) is a steroid alkaloid extracted from a traditional Chinese medicine,Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α) and nuclear respiratory factor 1 (NRF1), as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment.
Disparities in Prevalence of Smoking and Smoking Cessation during Pregnancy: A Population-Based Study
Authors: Dias-Damé Josiane L. , Cesar Juraci A.
Published: May 2015

Objective. To examine time trends in prevalence of smoking and smoking cessation during pregnancy by family income, maternal level of education, skin color, and age.Methods. We conducted three population-based surveys in 2007, 2010, and 2013 with newly delivered mothers living in the municipality of Rio Grande, Southern Brazil. Data were collected using questionnaires administered after delivery in all (two) maternity units in the city, at Dr. Miguel Riet Corrêa Júnior Hospital and at Santa Casa de Misericórdia. Time trends were analyzed using chi-square test for linear trend.Results. Data of 7,572 women showed that the prevalence of smoking before pregnancy decreased from 28% (26.2–29.7) in 2007 to 22% (20.8–24.0) in 2013 (P<0.001). Prevalence of smoking during pregnancy decreased from 22% (20.4–23.7) in 2007 to 18% (16.6–19.5) in 2013 (P<0.001). This reduction varied across income ranging from 17% (poorest) to 35% (richest) (P<0.001). The lower the income, the higher the smoking prevalence during pregnancy. Smoking cessation was more prevalent among women of higher level of education and income.Conclusions. Smoking before and during pregnancy is still highly prevalent and the prevalence of cessation is low pointing to a need to strengthen actions targeting low-income, less educated, black pregnant women.
A Hybrid Solvers Enhanced Integral Equation Domain Decomposition Method for Modeling of Electromagnetic Radiation
Authors: Zhao Ran , Hu Jun , Guo Han , Jiang Ming , Nie Zai-ping
Published: May 2015

The hybrid solvers based on integral equation domain decomposition method (HS-DDM) are developed for modeling of electromagnetic radiation. Based on the philosophy of “divide and conquer,” the IE-DDM divides the original multiscale problem into many closed nonoverlapping subdomains. For adjacent subdomains, the Robin transmission conditions ensure the continuity of currents, so the meshes of different subdomains can be allowed to be nonconformal. It also allows different fast solvers to be used in different subdomains based on the property of different subdomains to reduce the time and memory consumption. Here, the multilevel fast multipole algorithm (MLFMA) and hierarchical (H-) matrices method are combined in the framework of IE-DDM to enhance the capability of IE-DDM and realize efficient solution of multiscale electromagnetic radiating problems. The MLFMA is used to capture propagating wave physics in large, smooth regions, while H-matrices are used to capture evanescent wave physics in small regions which are discretized with dense meshes. Numerical results demonstrate the validity of the HS-DDM.
Multivariate Analysis of the Ocular Response Analyzer’s Corneal Deformation Response Curve for Early Keratoconus Detection
Authors: Galletti Jonatán D. , Ruiseñor Vázquez Pablo R. , Fuentes Bonthoux Fernando , Pförtner Tomás , Galletti Jeremías G.
Published: May 2015

Purpose. To thoroughly analyze corneal deformation responses curves obtained by Ocular Response Analyzer (ORA) testing in order to improve subclinical keratoconus detection.Methods. Observational case series of 87 control and 73 subclinical keratoconus eyes. Examination included corneal topography, tomography, and biomechanical testing with ORA. Factor analysis, logistic regression, and receiver operating characteristic curves were used to extract combinations of 45 corneal waveform descriptors. Main outcome measures were corneal-thickness-corrected corneal resistance factor (ccCRF), combinations of corneal descriptors, and their diagnostic performance.Results. Thirty-seven descriptors differed significantly in means between groups, and among them ccCRF afforded the highest individual diagnostic performance. Factor analysis identified first- and second-peak related descriptors as the most variable one. However, conventional biomechanical descriptors corneal resistance factor and hysteresis differed the most between control and keratoconic eyes. A combination of three factors including several corneal descriptors did not show better diagnostic performance than a combination of conventional indices.Conclusion. Multivariate analysis of ORA signals did not surpass simpler models in subclinical keratoconus detection, and there is considerable overlap between normal and ectatic eyes irrespective of the analysis model. Conventional biomechanical indices seem to already provide the best performance when appropriately considered.
Evaluation of Midnight Salivary Cortisol as a Predictor Factor for Common Carotid Arteries Intima Media Thickness in Patients with Clinically Inapparent Adrenal Adenomas
Authors: Reimondo Giuseppe , Allasino Barbara , Coletta Marcella , Pia Anna , Peraga Giulia , Zaggia Barbara , Massaglia Chiara , Paccotti Piero , Terzolo Massimo
Published: May 2015

Purpose. The aim of the present study was to investigate the atherosclerotic vascular damage in a consecutive series of patients with AI and to correlate it with MSC.Methods. We studied 32 patients with AI matched with control subjects for age, sex, and cardiovascular risk factors. Either patients or control subjects underwent MSC measurement as outpatients and carotid arteries ultrasound (US) imaging studies.Results. The patients with AI had higher mean carotid artery IMT values and higher MSC levels than control subjects. In a multivariate analysis performed in AI age was the best predictor for IMT. We have stratified patients and control subjects by age (<60 yrs and ≥60 yrs). The patients showed significantly higher MSC levels than controls in both groups, whereas significantly higher IMT values were observed only in older subjects.Conclusions. Patients with AI have signs of accelerated atherosclerosis. Patients older than 60 years seem more susceptible to the possible detrimental effect of subclinical hypercortisolism on cardiovascular system. The MSC levels are not a strong predictor of the accelerated atherosclerosis, but they seem to indicate the subtle but not autonomous cortisol excess that may potentially raise the cardiovascular risk.
An Energy-Efficient and Relay Hop Bounded Mobile Data Gathering Algorithm in Wireless Sensor Networks
Authors: Chen Ling , Wang Jianxin , Peng Xiaoqing , Kui Xiaoyan
Published: May 2015

Recent studies reveal that great benefit can be achieved by employing mobile collectors to gather data in wireless sensor networks. Since the mobile collector can traverse the transmission range of each sensor, the energy of nodes may be saved near maximally. However, for directly receiving data packet from every node, the length of mobile collector route should be very long. Hence it may significantly increase the data gathering latency. To solve this problem, several algorithms have been proposed. One of them called BRH-MDG found that data gathering latency can be effectively shortened by performing proper local aggregation via multihop transmissions and then uploading the aggregated data to the mobile collector. But, the BRH-MDG algorithm did not carefully analyze and optimize the energy consumption of the entire network. In this paper, we propose a mathematical model for the energy consumption of the LNs and present a new algorithm called EEBRHM. The simulation results show that under the premise of bounded relay hop, compared with BRH-MDG, EEBRHM can prolong the networks lifetime by 730%.