bluuebunny/crossref_metadata_2025 huggingface dataset:
An experimental study of data retention behavior in modern DRAM devices
Authors: Liu Jamie , Jaiyen Ben , Kim Yoongu , Wilkerson Chris , Mutlu Onur
Published: July 2013

DRAM cells store data in the form of charge on a capacitor. This charge leaks off over time, eventually causing data to be lost. To prevent this data loss from occurring, DRAM cells must be periodically refreshed. Unfortunately, DRAM refresh operations waste energy and also degrade system performance by interfering with memory requests. These problems are expected to worsen as DRAM density increases.

The amount of time that a DRAM cell can safely retain data without being refreshed is called the cell's
retention time
. In current systems, all DRAM cells are refreshed at the rate required to guarantee the integrity of the cell with the shortest retention time, resulting in unnecessary refreshes for cells with longer retention times. Prior work has proposed to reduce unnecessary refreshes by exploiting differences in retention time among DRAM cells; however, such mechanisms require knowledge of each cell's retention time.

In this paper, we present a comprehensive quantitative study of retention behavior in modern DRAMs. Using a temperature-controlled FPGA-based testing platform, we collect retention time information from 248 commodity DDR3 DRAM chips from five major DRAM vendors. We observe two significant phenomena:
data pattern dependence
, where the retention time of each DRAM cell is significantly affected by the data stored in other DRAM cells, and
variable retention time
, where the retention time of some DRAM cells changes unpredictably over time. We discuss possible physical explanations for these phenomena, how their magnitude may be affected by DRAM technology scaling, and their ramifications for DRAM retention time profiling mechanisms.
Improving virtualization in the presence of software managed translation lookaside buffers
Authors: Chang Xiaotao , Franke Hubertus , Ge Yi , Liu Tao , Wang Kun , Xenidis Jimi , Chen Fei , Zhang Yu
Published: July 2013

Virtualization has become an important technology that is used across many platforms, particularly servers, to increase utilization, multi-tenancy and security. Virtualization introduces additional overhead that often relates to memory management, interrupt handling and hypervisor mode switching. Among those, memory management and translation lookaside buffer (TLB) management have been shown to have a significant impact on the performance of systems. Two principal mechanisms for TLB management exist in today's systems, namely software and hardware managed TLBs. In this paper, we analyze and quantify the overhead of a pure software virtualization that is implemented over a software managed TLB. We then describe our design of hardware extensions to support virtualization in systems with software managed TLBs to remove the most dominant overheads. These extensions were implemented in the Power embedded A2 core, which is used in the PowerEN and in the Blue Gene/Q processors. They were used to implement a KVM port. We evaluate each of these hardware extensions to determine their overall contributions to performance and efficiency. Collectively these extensions demonstrate an average improvement of 232% over a pure software implementation.
Triggered instructions
Authors: Parashar Angshuman , Pellauer Michael , Adler Michael , Ahsan Bushra , Crago Neal , Lustig Daniel , Pavlov Vladimir , Zhai Antonia , Gambhir Mohit , Jaleel Aamer , Allmon Randy , Rayess Rachid , Maresh Stephen , Emer Joel
Published: July 2013

In this paper, we present
triggered instructions
, a novel control paradigm for arrays of
processing elements
(PEs) aimed at exploiting spatial parallelism. Triggered instructions completely eliminate the program counter and allow programs to transition concisely between states without explicit branch instructions. They also allow efficient reactivity to inter-PE communication traffic. The approach provides a unified mechanism to avoid
over-serialized
execution, essentially achieving the effect of techniques such as dynamic instruction reordering and multithreading, which each require distinct hardware mechanisms in a traditional sequential architecture.

Our analysis shows that a triggered-instruction based spatial accelerator can achieve 8X greater area-normalized performance than a traditional general-purpose processor. Further analysis shows that triggered control reduces the number of static and dynamic instructions in the critical paths by 62% and 64% respectively over a program-counter style spatial baseline, resulting in a speedup of 2.0X.
Utility-based acceleration of multithreaded applications on asymmetric CMPs
Authors: Joao José A. , Suleman M. Aater , Mutlu Onur , Patt Yale N.
Published: July 2013

Asymmetric Chip Multiprocessors (ACMPs) are becoming a reality. ACMPs can speed up parallel applications if they can identify and accelerate code segments that are critical for performance. Proposals already exist for using coarse-grained thread scheduling and fine-grained bottleneck acceleration. Unfortunately, there have been no proposals offered thus far to decide which code segments to accelerate in cases where both coarse-grained thread scheduling and fine-grained bottleneck acceleration could have value. This paper proposes Utility-Based Acceleration of Multithreaded Applications on Asymmetric CMPs (UBA), a cooperative software/hardware mechanism for identifying and accelerating the most likely critical code segments from a set of multithreaded applications running on an ACMP. The key idea is a new Utility of Acceleration metric that quantifies the performance benefit of accelerating a bottleneck or a thread by taking into account both the criticality and the expected speedup. UBA outperforms the best of two state-of-the-art mechanisms by 11% for single application workloads and by 7% for two-application workloads on an ACMP with 52 small cores and 3 large cores.
Exploring memory consistency for massively-threaded throughput-oriented processors
Authors: Hechtman Blake A. , Sorin Daniel J.
Published: July 2013

We re-visit the issue of hardware consistency models in the new context of massively-threaded throughput-oriented processors (MTTOPs). A prominent example of an MTTOP is a GPGPU, but other examples include Intel's MIC architecture and some recent academic designs. MTTOPs differ from CPUs in many significant ways, including their ability to tolerate latency, their memory system organization, and the characteristics of the software they run. We compare implementations of various hardware consistency models for MTTOPs in terms of performance, energy-efficiency, hardware complexity, and programmability. Our results show that the choice of hardware consistency model has a surprisingly minimal impact on performance and thus the decision should be based on hardware complexity, energy-efficiency, and programmability. For many MTTOPs, it is likely that even a simple implementation of sequential consistency is attractive.
Maximizing SIMD resource utilization in GPGPUs with SIMD lane permutation
Authors: Rhu Minsoo , Erez Mattan
Published: July 2013

Current GPUs maintain high programmability by abstracting the SIMD nature of the hardware as independent concurrent threads of control with hardware responsible for generating predicate masks to utilize the SIMD hardware for different flows of control. This dynamic masking leads to poor utilization of SIMD resources when the control of different threads in the same SIMD group diverges. Prior research suggests that SIMD groups be formed dynamically by compacting a large number of threads into groups, mitigating the impact of divergence. To maintain hardware efficiency, however, the alignment of a thread to a SIMD lane is fixed, limiting the potential for compaction. We observe that control frequently diverges in a manner that prevents compaction because of the way in which the fixed alignment of threads to lanes is done. This paper presents an in-depth analysis on the causes for ineffective compaction. An important observation is that in many cases, control diverges because of programmatic branches, which do not depend on input data. This behavior, when combined with the default mapping of threads to lanes, severely restricts compaction. We then propose SIMD lane permutation (SLP) as an optimization to expand the applicability of compaction in such cases of lane alignment. SLP seeks to rearrange how threads are mapped to lanes to allow even programmatic branches to be compacted effectively, improving SIMD utilization up to 34% accompanied by a maximum 25% performance boost.
CPU transparent protection of OS kernel and hypervisor integrity with programmable DRAM
Authors: Liu Ziyi , Lee JongHyuk , Zeng Junyuan , Wen Yuanfeng , Lin Zhiqiang , Shi Weidong
Published: July 2013

Increasingly, cyber attacks (e.g., kernel rootkits) target the inner rings of a computer system, and they have seriously undermined the integrity of the entire computer systems. To eliminate these threats, it is imperative to develop innovative solutions running below the attack surface. This paper presents MGuard, a new most inner ring solution for inspecting the system integrity that is directly integrated with the DRAM DIMM devices. More specifically, we design a programmable guard that is integrated with the advanced memory buffer of FB-DIMM to continuously monitor all the memory traffic and detect the system integrity violations. Unlike the existing approaches that are either snapshot-based or lack compatibility and flexibility, MGuard
continuously
monitors the integrity of all the outer rings including both OS kernel and hypervisor of interest, with a greater extendibility enabled by a programmable interface. It offers a hardware drop-in solution transparent to the host CPU and memory controller. Moreover, MGuard is isolated from the host software and hardware, leading to strong security for remote attackers. Our simulation-based experimental results show that MGuard introduces no speed overhead, and is able to detect nearly all the OS-kernel and hypervisor control data related rootkits we tested.
QuickSAN
Authors: Caulfield Adrian M. , Swanson Steven
Published: July 2013

Solid State Disks (SSDs) based on flash and other non-volatile memory technologies reduce storage latencies from 10s of milliseconds to 10s or 100s of microseconds, transforming previously inconsequential storage overheads into performance bottlenecks. This problem is especially acute in storage area network (SAN) environments where complex hardware and software layers (distributed file systems, block severs, network stacks, etc.) lie between applications and remote data. These layers can add hundreds of microseconds to requests, obscuring the performance of both flash memory and faster, emerging non-volatile memory technologies.

We describe QuickSAN, a SAN prototype that eliminates most software overheads and significantly reduces hardware overheads in SANs. QuickSAN integrates a network adapter into SSDs, so the SSDs can communicate directly with one another to service storage accesses as quickly as possible. QuickSAN can also give applications direct access to both local and remote data without operating system intervention, further reducing software costs. Our evaluation of QuickSAN demonstrates remote access latencies of 20
μ
s for 4 KB requests, bandwidth improvements of as much as 163x for small accesses compared with an equivalent iSCSI implementation, and 2.3-3.0x application level speedup for distributed sorting. We also show that QuickSAN improves energy efficiency by up to 96% and that QuickSAN's networking connectivity allows for improved cluster-level energy efficiency under varying load.
Criticality stacks
Authors: Du Bois Kristof , Eyerman Stijn , Sartor Jennifer B. , Eeckhout Lieven
Published: July 2013

Analyzing multi-threaded programs is quite challenging, but is necessary to obtain good multicore performance while saving energy. Due to synchronization, certain threads make others wait, because they hold a lock or have yet to reach a barrier. We call these
critical threads
, i.e., threads whose performance is determinative of program performance as a whole. Identifying these threads can reveal numerous optimization opportunities, for the software developer and for hardware.

In this paper, we propose a new metric for assessing thread criticality, which combines both how much time a thread is performing useful work and how many co-running threads are waiting. We show how thread criticality can be calculated online with modest hardware additions and with low overhead. We use our metric to create
criticality stacks
that break total execution time into each thread's criticality component, allowing for easy visual analysis of parallel imbalance.

To validate our criticality metric, and demonstrate it is better than previous metrics, we scale the frequency of the most critical thread and show it achieves the largest performance improvement. We then demonstrate the broad applicability of criticality stacks by using them to perform three types of optimizations: (1) program analysis to remove parallel bottlenecks, (2) dynamically identifying the most critical thread and accelerating it using frequency scaling to improve performance, and (3) showing that accelerating only the most critical thread allows for targeted energy reduction.
A new perspective for efficient virtual-cache coherence
Authors: Kaxiras Stefanos , Ros Alberto
Published: July 2013

Coherent shared virtual memory (cSVM) is highly coveted for heterogeneous architectures as it will simplify programming across different cores and manycore accelerators. In this context, virtual L1 caches can be used to great advantage, e.g., saving energy consumption by eliminating address translation for hits. Unfortunately, multicore virtual-cache coherence is complex and costly because it requires reverse translation for any coherence request directed towards a virtual L1. The reason is the ambiguity of the virtual address due to the possibility of synonyms. In this paper, we take a radically different approach than all prior work which is focused on reverse translation. We examine the problem from the perspective of the coherence protocol. We show that if a coherence protocol adheres to certain conditions, it operates effortlessly with virtual caches, without requiring reverse translations even in the presence of synonyms. We show that these conditions hold in a new class of simple and efficient request-response protocols that use both self-invalidation and self-downgrade. This results in a new solution for virtual-cache coherence, significantly less complex and more efficient than prior proposals. We study design choices for TLB placement under our proposal and compare them against those under a directory-MESI protocol. Our approach allows for choices that are particularly effective as for example combining all per-core TLBs in a single logical TLB in front of the last level cache. Significant area, energy, and performance benefits ensue as a result of simplifying the entire multicore memory organization.
QuickRec
Authors: Pokam Gilles , Danne Klaus , Pereira Cristiano , Kassa Rolf , Kranich Tim , Hu Shiliang , Gottschlich Justin , Honarmand Nima , Dautenhahn Nathan , King Samuel T. , Torrellas Josep
Published: July 2013

There has been significant interest in hardware-assisted deterministic Record and Replay (RnR) systems for multithreaded programs on multiprocessors. However, no proposal has implemented this technique in a hardware prototype with full operating system support. Such an implementation is needed to assess RnR practicality.

This paper presents
QuickRec
, the first multicore Intel Architecture (IA) prototype of RnR for multithreaded programs. QuickRec is based on
QuickIA
, an Intel emulation platform for rapid prototyping of new IA extensions. QuickRec is composed of a Xeon server platform with FPGA-emulated second-generation Pentium cores, and
Capo3
, a full software stack for managing the recording hardware from within a modified Linux kernel.

This paper's focus is understanding and evaluating the implementation issues of RnR on a real platform. Our effort leads to some lessons learned, as well as to some pointers for future research. We demonstrate that RnR can be implemented efficiently on a real multicore IA system. In particular, we show that the rate of memory log generation is insignificant, and that the recording hardware has negligible performance overhead. However, the software stack incurs an average recording overhead of nearly 13%, which must be reduced to enable
always-on
use of RnR.
Deubiquitylases From Genes to Organism
Authors: Clague Michael J. , Barsukov Igor , Coulson Judy M. , Liu Han , Rigden Daniel J. , Urbé Sylvie
Published: July 2013

Ubiquitylation is a major posttranslational modification that controls most complex aspects of cell physiology. It is reversed through the action of a large family of deubiquitylating enzymes (DUBs) that are emerging as attractive therapeutic targets for a number of disease conditions. Here, we provide a comprehensive analysis of the complement of human DUBs, indicating structural motifs, typical cellular copy numbers, and tissue expression profiles. We discuss the means by which specificity is achieved and how DUB activity may be regulated. Generically DUB catalytic activity may be used to 1) maintain free ubiquitin levels, 2) rescue proteins from ubiquitin-mediated degradation, and 3) control the dynamics of ubiquitin-mediated signaling events. Functional roles of individual DUBs from each of five subfamilies in specific cellular processes are highlighted with an emphasis on those linked to pathological conditions where the association is supported by whole organism models. We then specifically consider the role of DUBs associated with protein degradative machineries and the influence of specific DUBs upon expression of receptors and channels at the plasma membrane.
Molecular Biology of Atherosclerosis
Authors: Hopkins Paul N.
Published: July 2013

At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-α and related family members leading to activation of NF-κB; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.
Placebo and the New Physiology of the Doctor-Patient Relationship
Authors: Benedetti Fabrizio
Published: July 2013

Modern medicine has progressed in parallel with the advancement of biochemistry, anatomy, and physiology. By using the tools of modern medicine, the physician today can treat and prevent a number of diseases through pharmacology, genetics, and physical interventions. Besides this materia medica, the patient's mind, cognitions, and emotions play a central part as well in any therapeutic outcome, as investigated by disciplines such as psychoneuroendocrinoimmunology. This review describes recent findings that give scientific evidence to the old tenet that patients must be both cured and cared for. In fact, we are today in a good position to investigate complex psychological factors, like placebo effects and the doctor-patient relationship, by using a physiological and neuroscientific approach. These intricate psychological factors can be approached through biochemistry, anatomy, and physiology, thus eliminating the old dichotomy between biology and psychology. This is both a biomedical and a philosophical enterprise that is changing the way we approach and interpret medicine and human biology. In the first case, curing the disease only is not sufficient, and care of the patient is of tantamount importance. In the second case, the philosophical debate about the mind-body interaction can find some important answers in the study of placebo effects. Therefore, maybe paradoxically, the placebo effect and the doctor-patient relationship can be approached by using the same biochemical, cellular and physiological tools of the materia medica, which represents an epochal transition from general concepts such as suggestibility and power of mind to a true physiology of the doctor-patient interaction.
The Relationship between Traditional Chinese Medicine and Modern Medicine
Authors: Dong Jingcheng
Published: July 2013

The essence of the traditional Chinese medicine has always been the most advanced and experienced therapeutic approach in the world. It has knowledge that can impact the direction of future modern medical development; still, it is easy to find simple knowledge with mark of times and special cultures. The basic structure of traditional Chinese medicine is composed of three parts: one consistent with modern medicine, one involuntarily beyond modern medicine, and one that needs to be further evaluated. The part that is consistent with modern medicine includes consensus on several theories and concepts of traditional Chinese medicine, and usage of several treatments and prescriptions of traditional Chinese medicine including commonly used Chinese herbs. The part that is involuntarily beyond modern medicine contains several advanced theories and important concepts of traditional Chinese medicine, relatively advanced treatments, formula and modern prescriptions, leading herbs, acupuncture treatment and acupuncture anesthesia of traditional Chinese medicine that affect modern medicine and incorporates massage treatment that has been gradually acknowledged by modern therapy. The part that needs to be further evaluated consists not only the knowledge of pulse diagnosis, prescription, and herbs, but also many other aspects of traditional Chinese medicine.
Wind Farm Power Forecasting
Authors: Haouas Nabiha , Bertrand Pierre R.
Published: July 2013

Forecasting annual wind power production is useful for the energy industry. Until recently, attention has only been paid to the mean annual wind power energy and statistical uncertainties on this forecasting. Recently, Bensoussan et al. (2012) have pointed that the annual wind power produced by one wind turbine is a Gaussian random variable under a reasonable set of assumptions. Moreover, they can derive both mean and quantiles of annual wind power produced by one wind turbine. The novelty of this work is the obtainment of similar results for estimating the annual wind farm power production. Eventually, we study the relationship between the power production for each turbine of the farm in order to avoid interaction between them.
Nonunion of the Medial Cuneiform: A Rare Case
Authors: Alemdar Celil , Uçar Bekir Yavuz , Yıldırım Azad , Kapukaya Ahmet
Published: July 2013

Isolated medial cuneiform fractures are quite rare. Conservative treatment is adequate in most cases, while deplaced or unstable fractures are treated surgically. Nonunion is seen extremely rarely after medial cuneiform fractures. There is only one case report in the literature. This case presented here is a 62-year-old male patient who had an isolated medial cuneiform fracture resulting from the impact of a falling metal object. Conservative treatment was performed initially. The patient was diagnosed as nonunion after physical and radiological examinations nine months after he presented to the outpatient clinic. Internal fixation with a mini plate and one staple after reduction was performed surgically. Defective region was filled with a 2 mL of autograft, and the operation was terminated.
Global Dynamics of HIV Infection of CD4+T Cells and Macrophages
Authors: Elaiw A. M. , Alsheri A. S.
Published: July 2013

We study the global dynamics of an HIV infection model describing the interaction of the HIV with CD4+T cells and macrophages. The incidence rate of virus infection and the growth rate of the uninfected CD4+T cells and macrophages are given by general functions. We have incorporated two types of distributed delays into the model to account for the time delay between the time the uninfected cells are contacted by the virus particle and the time for the emission of infectious (matures) virus particles. We have established a set of conditions which are sufficient for the global stability of the steady states of the model. Using Lyapunov functionals and LaSalle's invariant principle, we have proven that if the basic reproduction numberR0is less than or equal to unity, then the uninfected steady state is globally asymptotically stable (GAS), and if the infected steady state exists, then it is GAS.
Applicability of Simplified Simulation Models for Perforation-Mediated Modified Atmosphere Packaging of Fresh Produce
Authors: Kwon Min-Ji , Jo Yun Hee , An Duck Soon , Lee Dong Sun
Published: July 2013

The comprehensive mass balances of differential equations involving gas diffusion and hydraulic convection through package perforation, gas permeation through polymeric film, and produce respiration have commonly been used to predict the atmosphere of perforated fresh produce packages. However, the predictions often suffer from instability, and to circumvent this problem, a simplified diffusion model that omits the convective gas transfer and empirical models based on experimental mass transfer data have been developed and investigated previously by several researchers. This study investigated the potential and limitations of the simplified diffusion model and two empirical models for predicting the atmosphere in perforated produce packages. The simplified diffusion model satisfactorily estimated the atmosphere inside the perforated packages of fresh produce under the aerobic conditions examined. Published empirical models of the mass transfer coefficients of the perforation seem to be valid only for the measured conditions and thus should be used carefully for that specific purpose.
A Generalized Regula Falsi Method for Finding Zeros and Extrema of Real Functions
Authors: Gomes Abel , Morgado José
Published: July 2013

Many zero-finding numerical methods are based on the Intermediate Value Theorem, which states that a zero of a real function is bracketed in a given interval if and have opposite signs; that is, . But, some zeros cannot be bracketed this way because they do not satisfy the precondition . For example, local minima and maxima that annihilate may not be bracketed by the Intermediate Value Theorem. In this case, we can always use a numerical method for bracketing extrema, checking then whether it is a zero of or not. Instead, this paper introduces a single numerical method, calledgeneralized regula falsi(GRF) method to determine both zeros and extrema of a function. Consequently, it differs from the standardregula falsi methodin that it is capable of finding any function zero in a given interval even when the Intermediate Value Theorem is not satisfied.
A Novel Case of Resolved Postherpetic Neuralgia with Subsequent Development of Trigeminal Neuralgia: A Case Report and Review of the Literature
Authors: Mason Alexander , Ayres Kristen , Burneikiene Sigita , Villavicencio Alan T. , Nelson E. Lee , Rajpal Sharad
Published: July 2013

A 72-year-old female patient is presented, who was diagnosed with herpes zoster along the left ophthalmic branch of the trigeminal nerve with associated cutaneous vesicles. The patient subsequently developed postherpetic neuralgia in the same dermatome, which, after remission, transformed into paroxysmal trigeminal pain. The two different symptom sets, with the former consistent with PHN and the later consistent with trigeminal neuralgia, were unique to our practice and the literature.
Death from Liver Failure despite Lamivudine Prophylaxis during R-CHOP Chemotherapy due to Rapid Emergence M204 Mutations
Authors: Win Lay Lay , Powis Jeff , Shah Hemant , Feld Jordan J. , Wong David K.
Published: July 2013

Background. Rapid and early emergence of clinically significant LAM resistance is thought to be unlikely during the first year of treatment, and as a result LAM is thought to be a reasonable choice as a first line agent for prophylaxis during chemotherapy.Aim. To report fatal HBV reactivation despite appropriate LAM prophylaxis in two previously treatment-naive individuals undergoing R-CHOP chemotherapy.Case Presentation. Case 1 is a 65-year-old man with chronic HBV infection: HBeAg-negative, HBV DNA 6.65E5 IU/mL, ALT 43 IU/L, and Fibroscan 4.4 kPa, consistent with F0, who was diagnosed with lymphoma that was treated with R-CHOP and LAM prophylaxis. HBV DNA fell to 2.18E1 IU/mL within 2 months of starting LAM. Four months after chemotherapy, despite ongoing LAM of 7-month duration with confirmed adherence, severe asymptomatic hepatitis was noted during routine monitoring with ALT 1019 IU/L, HBeAg negative, HBV DNA 1.43E7 IU/mL, and genotyping confirmed L80I and M204I mutations. He died 14 days after flare diagnosis despite a switch to tenofovir (HBV DNA had fallen to 1.94E5 IU/mL 2 weeks after starting tenofovir). Case 2 is a 50-year-old man who was found to have HBeAg-negative hepatitis B, ALT 37 IU/L, and no clinical features of cirrhosis (platelets 283, APRI 0.19) after lymphoma diagnosis. Lymphoma was treated with R-CHOP and LAM prophylaxis. Pretreatment HBV DNA was not done but was 8.90E4 IU/mL 3 weeks after starting LAM and 3.96E3 IU/mL 3 months after starting LAM. Two months after chemotherapy, despite ongoing LAM of 7-month duration with confirmed adherence, severe symptomatic hepatitis presenting with jaundice, abdominal pain, and confusion was noted. ALT 902 IU/L, HBeAg negative, HBV DNA 1.02E8 IU/mL, and genotyping confirmed L80I, M80V, and M204V/S mutations. He died 3 days after flare diagnosis despite the addition of tenofovir.Conclusion. Lamivudine should not be used for prophylaxis of patients with chronic hepatitis B with detectable HBV DNA undergoing chemotherapy with rituximab containing cytotoxic chemotherapy even if they have never had exposure to lamivudine in the past. In this setting, lamivudine failure due to resistance can develop quickly leading to liver failure that cannot be salvaged with tenofovir. Whether LAM is safe for prophylaxis with rituximab-based cytotoxic chemotherapy for patients with undetectable HBV DNA is unknown, but agents with a high barrier to resistance may be preferable.
Ocular Risk Factors for Exudative AMD: A Novel Semiautomated Grading System
Authors: Marques João Pedro , Costa Miguel , Melo Pedro , Oliveira Carlos Manta , Pires Isabel , Cachulo Maria Luz , Figueira João , Silva Rufino
Published: July 2013

Purpose. To evaluate the contribution of the ocular risk factors in the conversion of the fellow eye of patients with unilateral exudative AMD, using a novel semiautomated grading system. Materials and Methods. Single-center, retrospective study including 89 consecutive patients with unilateral exudative AMD and ≥3 years of followup.
Baseline color fundus photographs were graded using an innovative grading software, RetmarkerAMD (Critical Health SA). Results. The follow-up period was 60.9±31.3 months. The occurrence of CNV was confirmed in 42 eyes (47.2%). The cumulative incidence of CNV was 23.6% at 2 years, 33.7% at 3 years, 39.3% at 5 years, and 47.2% at 10 years, with a mean annual incidence of 12.0% (95% CI=
0.088–0.162). The absolute number of drusen in the central 1000 and 3000 μm (P<0.05) and the absolute number of drusen ≥125 µm in the central 3000 and 6000 µm (P<0.05) proved to be significant risk factors for CNV. Conclusion. The use of quantitative variables in the determination of the OR of developing CNV allowed the establishment of significant risk factors for neovascularization. The long follow-up period and the innovative methodology reinforce the value of our results. This trial is registered with ClinicalTrials.gov NCT00801541.
Surface Defect Target Identification on Copper Strip Based on Adaptive Genetic Algorithm and Feature Saliency
Authors: Zhang Xuewu , Li Wei , Xi Ji , Zhang Zhuo , Fan Xinnan
Published: July 2013

To enhance the stability and robustness of visual inspection system (VIS), a new surface defect target identification method for copper strip based on adaptive genetic algorithm (AGA) and feature saliency is proposed. First, the study uses gray level cooccurrence matrix (GLCM) and HU invariant moments for feature extraction. Then, adaptive genetic algorithm, which is used for feature selection, is evaluated and discussed. In AGA, total error rates and false alarm rates are integrated to calculate the fitness value, and the probability of crossover and mutation is adjusted dynamically according to the fitness value. At last, the selected features are optimized in accordance with feature saliency and are inputted into a support vector machine (SVM). Furthermore, for comparison, we conduct experiments using the selected optimal feature subsequence (OFS) and the total feature sequence (TFS) separately. The experimental results demonstrate that the proposed method can guarantee the correct rates of classification and can lower the false alarm rates.
Filter Cake and Vinasse as Fertilizers Contributing to Conservation Agriculture
Authors: Prado Renato de Mello , Caione Gustavo , Campos Cid Naudi Silva
Published: July 2013

Utilising organic residues in agriculture contributes to the conservation of natural resources by recycling carbon and mineral elements. Organic residues produced by the sugar and alcohol agroindustries have great potential for use in conservation agriculture. The production of sugar and alcohol generates large quantities of byproducts, such as filter cake and vinasse, which can be used as soil improvers and substitutes for inorganic phosphorus and potassium fertilizers. However, the use of these residues in agriculture requires specific recommendations for each pedoclimatic condition to prevent environmental damage.
Survival Analysis Based on Clinicopathological Data from a Single Institution: Chemotherapy Intensity Would Be Enhanced in Patients with Positive Hormone Receptors and Positive HER2 in China Who Cannot Afford the Target Therapy
Authors: Li Jianyi , Jia Shi , Zhang Wenhai , Zhang Yang , Fei Xiang , Tian Rui
Published: July 2013

Background. Immunohistochemical markers were often used to classify breast cancer into subtypes. The aim of this study was to estimate death and tumor progression for patients with the major subtypes of breast cancer as classified using immunohistochemical assay and to investigate the patterns of benefit from the therapies over the past years. Methods. The study population included primary, operable 199 invasive ductal breast cancer patients, with the median age of 51.1 years old. All patients underwent local and/or systemic treatments. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. The expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki67 was analyzed by immunohistochemistry. All patients were classified into the following categories: luminal A, luminal B, HER2 overexpression, and triple-negative subtypes. Result. The median follow-up time was 33 months. Luminal A tumors had the lowest rate of tumor progression (0%, P=0.006), while luminal B, HER2 over-expression, and triple-negative subtypes were associated with an increased risk of tumor progression (15.4, 19.2, 15.4%). Clinicopathological subtypes retained independent prognostic significance (P=0.008). There were significant differences by Cox model analyzed in age, menopause, lymph node metastasis, and HER2 for the event of death and tumor progression (P<0.05), and there were significant differences only in chemotherapy for the event, respectively (P<0.05). Conclusion. Clinicopathological subtypes of breast cancer could robustly identify the risk of death and tumor progression and were significant in making therapeutic decision. HER2 was the important poor indicator. The chemotherapy intensity would be enhanced for patients with luminal B, especially for HER2 over-expression subgroup.
Preparation of AgI/Silica/Poly(Ethylene Glycol) Nanoparticle Colloid Solution and X-Ray Imaging Using It
Authors: Kobayashi Yoshio , Ayame Tetsuya , Nakagawa Tomohiko , Kubota Yohsuke , Gonda Kohsuke , Ohuchi Noriaki
Published: July 2013

This work performed X-ray imaging of mouse by using aqueous colloid solution of AgI nanoparticles coated with silica (AgI/SiO2) and then surface-modified with poly(ethylene glycol) (PEG) (AgI/SiO2/PEG). A colloid solution of AgI nanoparticles was prepared by mixing silver perchlorate and potassium iodide in water. The AgI nanoparticles were surface-modified with 3-mercaptopropyltrimethoxysilane and then were silica-coated by a sol-gel reaction between tetraethylorthosilicate and H2O catalyzed with NaOH in ethanol. The AgI/SiO2 particle surface was modified with PEG by using methoxy PEG silane CH3OCH2CH2OnCH2CONHC3H6SiOC2H53. The AgI/SiO2/PEG colloid solution revealed a computed tomography value as high as 1343.6 HU at an iodine concentration of 0.1 M, which was higher than a commercial X-ray contrast agent with the same iodine concentration. Tissues of mouse could be imaged by injecting the concentrated colloid solution into them.
Harmony Search Based Parameter Ensemble Adaptation for Differential Evolution
Authors: Mallipeddi Rammohan
Published: July 2013

In differential evolution (DE) algorithm, depending on the characteristics of the problem at hand and the available computational resources, different strategies combined with a different set of parameters may be effective. In addition, a single, well-tuned combination of strategies and parameters may not guarantee optimal performance because different strategies combined with different parameter settings can be appropriate during different stages of the evolution. Therefore, various adaptive/self-adaptive techniques have been proposed to adapt the DE strategies and parameters during the course of evolution. In this paper, we propose a new parameter adaptation technique for DE based on ensemble approach and harmony search algorithm (HS). In the proposed method, an ensemble of parameters is randomly sampled which form the initial harmony memory. The parameter ensemble evolves during the course of the optimization process by HS algorithm. Each parameter combination in the harmony memory is evaluated by testing them on the DE population. The performance of the proposed adaptation method is evaluated using two recently proposed strategies (DE/current-to-pbest/bin and DE/current-to-gr_best/bin) as basic DE frameworks. Numerical results demonstrate the effectiveness of the proposed adaptation technique compared to the state-of-the-art DE based algorithms on a set of challenging test problems (CEC 2005).
Long-Term Exercise and Risk of Metabolic and Cardiac Diseases: The Erlangen Fitness and Prevention Study
Authors: Kemmler Wolfgang , von Stengel Simon , Bebenek Michael , Kalender Willi A.
Published: July 2013

In female subjects, ageing and the menopausal transition contribute to a rapid increase of metabolic and cardiac risk factors. Exercise may be an option to positively impact various risk factors prone to severe metabolic and cardiac diseases and events. This study was conducted to determine the long-term effect of a multipurpose exercise program on metabolic and cardiac risk scores in postmenopausal women. 137 osteopenic Caucasian females (55.4±3.2 yrs), 1–8 years postmenopausal, were included in the study. Eighty-six subjects joined the exercise group (EG) and performed an intense multipurpose exercise program which was carefully supervised during the 12-year period, while 51 females maintained their habitual physical activity (CG). Main outcome measures were 10-year coronary heart disease risk (10 y CHD risk), metabolic syndromeZ-score (MetS Index), and 10-year myocardial infarction risk (10 y hard CHD risk). Significant between-group differences all in favor of the EG were determined for 10 y-CHD risk (EG:2.65±2.09% versus CG:5.40±3.30%;P=0.001), MetS-Index (EG:−0.42±1.03% versus CG:1.61±1.88;P=0.001), and 10 y-hard-CHD risk (EG:2.06±1.17% versus CG:3.26±1.31%;P=0.001). Although the nonrandomized design may prevent definite evidence, the intense multi-purpose exercise program determined the long-term efficacy and feasibility of an exercise program to significantly impact metabolic and cardiac risk scores in postmenopausal women. This trial is registered with ClinicalTrials.govNCT01177761.
Numerical Analysis of the Frictional Characteristics of a Magnetic Suspended Flying Vehicle
Authors: Wang Xiaoguang , Chen Yongwei
Published: July 2013

This paper explores a novel approach to the calculation of the dynamic magnetic field under the feedback control and analyzes the frictional characteristics of a magnetic suspended flying vehicle by ANSYS. The numerical calculation result is compared with the experimental data to verify the accuracy and the effectiveness of the approach which suggests a method of the calculation of the dynamic magnetic field under the feedback control by ANSYS. Research results indicate that the equivalent friction coefficient of the magnetic suspended flying vehicle is not a constant which is not only related to the running speed and the weight of the vehicle but also to the resistivity of material of the guide rail and some control parameters of the vehicle. In other words, the smaller the air gap of the vehicle, the smaller the equivalent friction force. The equivalent friction force increases as the running speed increases. With the same air gap and running speed, the equivalent friction force increases with the increase of the weight of the vehicle.
Rotenone Upregulates Alpha-Synuclein and Myocyte Enhancer Factor 2D Independently from Lysosomal Degradation Inhibition
Authors: Sala Gessica , Arosio Alessandro , Stefanoni Giovanni , Melchionda Laura , Riva Chiara , Marinig Daniele , Brighina Laura , Ferrarese Carlo
Published: July 2013

Dysfunctions of chaperone-mediated autophagy (CMA), the main catabolic pathway for alpha-synuclein, have been linked to the pathogenesis of Parkinson’s disease (PD). Since till now there is limited information on how PD-related toxins may affect CMA, in this study we explored the effect of mitochondrial complex I inhibitor rotenone on CMA substrates, alpha-synuclein and MEF2D, and effectors, lamp2A and hsc70, in a human dopaminergic neuroblastoma SH-SY5Y cell line. Rotenone induced an upregulation of alpha-synuclein and MEF2D protein levels through the stimulation of theirde novosynthesis rather than through a reduction of their CMA-mediated degradation. Moreover, increased MEF2D transcription resulted in higher nuclear protein levels that exert a protective role against mitochondrial dysfunction and oxidative stress. These results were compared with those obtained after lysosome inhibition with ammonium chloride. As expected, this toxin induced the cytosolic accumulation of both alpha-synuclein and MEF2D proteins, as the result of the inhibition of their lysosome-mediated degradation, while, differently from rotenone, ammonium chloride decreased MEF2D nuclear levels through the downregulation of its transcription, thus reducing its protective function. These results highlight that rotenone affects alpha-synuclein and MEF2D protein levels through a mechanism independent from lysosomal degradation inhibition.
Heparin and Related Drugs: Beyond Anticoagulant Activity
Authors: Page Clive
Published: July 2013

Heparin has been widely used as an anticoagulant for more than 80 years. However, there is now considerable evidence that heparin also possesses anti-inflammatory activity, both experimentally and clinically. Importantly in many instances, the anti-inflammatory actions of heparin are independent of anticoagulant activity raising the possibility of developing novel drugs based on heparin that retain the anti-inflammatory activity. Heparin exhibits anti-inflammatory activities via a variety of mechanisms including neutralization of cationic mediators, inhibition of adhesion molecules, and the inhibition of heparanase, all involved in leukocyte recruitment into tissues. It is anticipated that furthering our understanding of the anti-inflammatory actions of heparin will lead to the development of novel anti-inflammatory drugs for a variety of clinical indications.
Drain Rate and Liquid Level Simulation in Blast Furnace Hearth Using Plant Data
Authors: Upadhyay Hemant , Kundu T. K.
Published: July 2013

Proper understanding and control of drainage of hot metal and slag from hearth are essential for a stable and efficient blast furnace operation. Various operational problems like irregular casting intervals, damage to lining, low blast intake, furnace pressurization, and so forth are normally encountered when liquid levels in the hearth exceed a critical limit where hearth coke and deadman start to float. Estimation of drain rate and liquid level in hearth needs to be simulated based on the operating parameters available as carrying out any direct measurement is extremely difficult due to the hostile conditions. Here, a mathematical model has been developed to simulate real-time liquid level and drainage behavior of the furnace hearth. Based on the computed drainage rate, production rate, and mass balance, the model is able to predict occurrence of slag-out time and cast close time which are in good agreement with the plant data.
Molecular Pathways: Human Leukocyte Antigen G (HLA-G)
Authors: Curigliano Giuseppe , Criscitiello Carmen , Gelao Lucia , Goldhirsch Aron
Published: July 2013

Human leukocyte antigen G (HLA-G) is a nonclassical MHC class I molecule that exerts important tolerogenic functions. Its main physiologic expression occurs in the placenta, where it participates in the maternal tolerance toward the fetus. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic lineage. It is expressed in various types of primary solid (melanoma, head and neck, lung, urogenital, gastrointestinal, and breast cancers) and hematologic malignancies (acute leukemia, lymphomas) and metastases. HLA-G ectopic expression is observed in cancer, suggesting that its expression is one strategy used by tumor cells to escape immune surveillance. In this review, we will focus on HLA-G expression in cancers and its association with the prognosis. We will highlight the underlying molecular mechanisms of impaired HLA-G expression, the immune tolerant function of HLA-G in tumors, and the potential diagnostic use of membrane-bound and soluble HLA-G as a biomarker to identify tumors and to monitor disease stage. As HLA-G is a potent immunoinhibitory molecule, its blockade remains an attractive therapeutic strategy against cancer. Elimination of HLA-G–expressing cancer cells would be important in the efficacy of anticancer therapies. Clin Cancer Res; 19(20); 5564–71. ©2013 AACR.