bluuebunny/crossref_metadata_2025 huggingface dataset:
Online thermal control methods for multiprocessor systems
Authors: Zanini Francesco , Atienza David , Jones Colin N. , Benini Luca , De Micheli Giovanni
Published: January 2013

With technological advances, the number of cores integrated on a chip is increasing. This in turn is leading to thermal constraints and thermal design challenges. Temperature gradients and hotspots not only affect the performance of the system but also lead to unreliable circuit operation and affect the lifetime of the chip. Meeting temperature constraints and reducing hotspots are critical for achieving reliable and efficient operation of complex multi-core systems.

In this article, we analyze the use of four of the most promising families of online control techniques for thermal management of multiprocessors system-on-chip (MPSoC). In particular, in our exploration, we aim at achieving an online smooth thermal control action that minimizes the performance loss as well as the computational and hardware overhead of embedding a thermal management system inside the MPSoC. The definition of the optimization problem to tackle in this work considers the thermal profile of the system, its evolution over time, and current time-varying workload requirements. Thus, this problem is formulated as a finite-horizon optimal control problem, and we analyze the control features of different online thermal control approaches. In addition, we implemented the policies on an MPSoC hardware simulation platform and performed experiments on a cycle-accurate model of the eight-core Niagara multi-core architecture using benchmarks ranging from Web-accessing to playing multimedia. Results show different trade-offs among the analyzed techniques regarding the thermal profile, the frequency setting, the power consumption, and the implementation complexity.
Thermal prediction and adaptive control through workload phase detection
Authors: Cochran Ryan , Reda Sherief
Published: January 2013

Elevated die temperature is a true limiter to the scalability of modern processors. With continued technology scaling in order to meet ever-increasing performance demands, it is no longer cost effective to design cooling systems that handle the worst-case thermal behaviors. Instead, cooling systems are designed to handle typical chip operation, while processors must detect and handle rare thermal emergencies. Most processors rely on measurements from integrated thermal sensors and dynamic thermal management (DTM) techniques in order to manage the trade-off between performance and thermal risk. Optimal management requires advanced knowledge of the thermal trajectory based on the current workload behaviors and operating conditions. In this work, we devise novel workload phase classification strategies that automatically discriminate among workload behaviors with respect to the thermal control response. We incorporate workload phase-detection and thermal models into a dynamic voltage and frequency scaling (DVFS) technique that can optimally control temperature during runtime based on thermal predictions. We demonstrate the effectiveness of our proposed techniques in predicting and adaptively controlling the thermal behavior of a real quad-core processor in response to a wide range of workloads. In comparison with state-of-the-art model predictive control (MPC) techniques in previous works on thermal prediction, we demonstrate a 5.8% improvement in instruction throughput with the same number of thermal violations. In comparison with simple proportional-integral (PI) feedback control techniques, we improve instruction throughput by 3.9%, while significantly reducing the number of thermal violations.
Compiler-in-the-loop exploration during datapath synthesis for higher quality delay-area trade-offs
Authors: Xydis Sotirios , Pekmestzi Kiamal , Soudris Dimitrios , Economakos George
Published: January 2013

Design space exploration during high-level synthesis targets the computation of those design solutions which form optimal trade-off points. This quest for optimal trade-offs has been focused on studying the impact of various architectural-level parameters during high-level synthesis algorithms, silently neglecting the trade-offs produced from the combined impact of behavioral-level together with architectural-level parameters. We propose a novel design space, exploration methodology that studies an extended instance of the solution space considering the effects of combining compiler- and architectural-level transformations. It is shown that exploring the design space in a global manner reveals new trade-off points, thus shifting towards higher quality design solutions. We use a combination of upper-bounding conditions together with gradient-based heuristic pruning to efficiently traverse the extended search space. Our exploration framework delivers significant quality improvements without compromising the optimality (Pareto accuracy) of the discovered solutions, together with significant runtime reductions compared to exploring exhaustively the solution space at every allocation scenario.
Verification work reduction methodology in low-power chip implementation
Authors: Kurimoto Masanori , Yamamoto Takeshi , Nakano Satoshi , Hanami Atsuto , Kondo Hiroyuki
Published: January 2013

In order to achieve satisfactory verification for complicated low-power demands in green products, we propose a verification work reduction methodology. It consists of three step, namely virtual, direct actual, and actual model simulations. Virtual low-power simulation inserts low-power cells, such as isolators or level shifters, virtually and simulates logical behavior for design under test (DUT) based on user-defined power mode. Direct actual low-power simulation replaces behavior models without non-logical pins for some of modules with actual models with non-logical pins, which are Vdd and Gnd, and simulates DUT in mixed level. Actual low-power simulation simulates DUT by using actual models with non-logical pins for all cells and hard macros. We introduce techniques which classify the type of the bugs on which we focus at each verification step and prevent the concerned bugs from leaking to the latter verification step as much as possible.

We applied our methodology to an actual chip and could reduce the total simulation period until tape-out by 38.8% and the total chip development period by 10%, compared with the conventional methodology.
SEU fault evaluation and characteristics for SRAM-based FPGA architectures and synthesis algorithms
Authors: Jing Naifeng , Lee Ju-Yueh , Feng Zhe , He Weifeng , Mao Zhigang , He Lei
Published: January 2013

Reliability has become an increasingly important concern for SRAM-based field programmable gate arrays (FPGAs). Targeting SEU (single event upset) in SRAM-based FPGAs, this article first develops an SEU evaluation framework that can quantify the failure sensitivity for each configuration bit during design time. This framework considers detailed fault behavior and logic masking on a post-layout FPGA application and performs logic simulation on various circuit elements for fault evaluation. Applying this framework on MCNC benchmark circuits, we first characterize SEUs with respect to different FPGA circuits and architectures, for example, bidirectional routing and unidirectional routing. We show that in both routing architectures, interconnects not only contribute to the lion's share of the SEU-induced functional failures, but also present higher failure rates per configuration bits than LUTs. Particularly, local interconnect multiplexers in logic blocks have the highest failure rate per configuration bit. Then, we evaluate three recently proposed SEU mitigation algorithms, IPD, IPF, and IPV, which are all logic resynthesis-based with little or no overhead on placement and routing. Different fault mitigating capabilities at the chip level are revealed, and it demonstrates that algorithms with explicit consideration for interconnect significantly mitigate the SEU at the chip level, for example, IPV achieves 61% failure rate reduction on average against IPF with about 15%. In addition, the combination of the three algorithms delivers over 70% failure rate reduction on average at the chip level. The experiments also reveal that in order to improve fault tolerance at the chip level, it is necessary for future fault mitigation algorithms to concern not only LUT or interconnect faults, but also their interactions. We envision that our framework can be used to cast more useful insights for more robust FPGA circuits, architectures, and better synthesis algorithms.
Discrete sizing for leakage power optimization in physical design
Authors: Mok Santiago , Lee John , Gupta Puneet
Published: January 2013

While sizing has been studied for over three decades, the absence of a common framework with which to compare methods has made progress difficult to measure. In this article, we compare popular sizing techniques in which gates are chosen from a discrete standard cell library and slew and interconnect effects are accounted for. The difference between sizing methods reduces from roughly 53% to 8% between best and worst case after slew propagation is taken into account. In our benchmarks, no one sizing technique consistently outperforms the others.
ECO cost measurement and incremental gate sizing for late process changes
Authors: Lee John , Gupta Puneet
Published: January 2013

Changes in the manufacturing process parameters may create timing violations in a design, making it necessary to perform an engineering change order (ECO) to correct these problems. We present a framework for performing incremental gate sizing for process changes late in the design cycle, and a method for creating initial designs that are robust to late process changes. This includes a method for measuring and estimating ECO cost and for transforming these costs into linear programming optimization problems. In the case of ECOs, the method reduces ECO costs on average, by 89% in changed area compared to a leading commercial tool. Furthermore, the robust initial designs are, on average, 55% less likely to need redesign in the future.
Flame Atomic Absorption Determination of Gold Ion in Aqueous Samples after Preconcentration Using 9‐Acridinylamine Functionalized γ‐Alumina Nanoparticles
Authors: Karimi Mohammad , Amani Vahid , Aboufazeli Forouzan , Lotfi Zadeh Zhad Hamid Reza , Sadeghi Omid , Najafi Ezzatollah
Published: January 2013

A simple and sensitive solid phase extraction utilizing 9‐acridinylamine functionalized alumina nanoparticles was developed, and their potential use for preconcentration and subsequent determination of gold by flame atomic absorption spectrometry (FAAS) was investigated. A number of parameters, namely, type, concentration, and volume of eluent, pH of the sample solution, flow rate of extraction, and volume of the sample, were evaluated. The effect of a variety of ions on preconcentration and recovery was also investigated. Gold ions were found to be recovered quantitatively at pH 3.0, with 0.1 mol L−1 thiourea in 2 mol L−1 H2SO4 as eluent. The limit of detection (LOD), defined as five times the standard deviation of the blank, was determined to be lower than 13.0 ppb. Under optimum conditions, the accuracy and precision (RSD%) of the method were >98.0 and <1.5%, respectively. To gauge its ability in terms of application to real samples, the proposed method was successfully applied for determination of gold concentration in waste water samples and one soil standard material, and satisfactory results were obtained.
Cycloaddition Reaction of Carbon Dioxide to Epoxides Catalyzed by Polymer‐Supported Quaternary Phosphonium Salts
Authors: Xiong Yubing , Bai Feng , Cui Zipeng , Guo Na , Wang Rongmin
Published: January 2013

Polymer‐supported quaternary phosphonium salt (PS‐QPS) was explored as effective catalyst for the coupling reaction of carbon dioxide with epoxides. The results indicated that cyclic carbonates with high yields (98.6%) and excellent selectivity (100%) could be prepared at the conditions of 5 MPa CO2, 150°C, and 6 h without the addition of organic solvents or cocatalysts. The effects of various reaction conditions on the catalytic performance were investigated in detail. The catalyst is applicable to a variety of epoxides, producing the corresponding cyclic carbonates in good yields. Furthermore, the catalyst could be recovered easily and reused for five times without loss of catalytic activity obviously. A proposed mechanism for synthesis of cyclic carbonate in the presence of PS‐QPS was discussed. The catalyst was characterized by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and Fourier transform infrared (FT‐IR) spectrum. It is believed that PS‐QPS is of great potential for CO2 fixation applications due to its unusual advantages, such as easy preparation, high activity and selectivity, stability, low cost, and reusability.
Molecular Classification of Hepatocellular Adenomas
Authors: Nault Jean Charles , Zucman Rossi Jessica
Published: January 2013

Hepatocellular adenomas (HCAs) are benign tumors developed in normal liver most frequently in women before menopause. HCAs lead to diagnostic pitfalls and several difficulties to assess the risk of malignant transformation in these young patients. Recent advances in basic knowledge have revealed a molecular classification related to risk factors, pathological features, and risk of transformation in hepatocellular carcinoma. Three major molecular pathways have been identified altered in specific HCA subgroups that are defined by either (1) inactivation of hepatocyte nuclear factor 1A (HNF1A) transcription factor, (2) activation of the WNT/β-catenin byCTNNB1mutations, or (3) activation of the IL6/STAT3 pathway by somatic mutation ofIL6ST,GNAS, orSTAT3. Here, we will review the different molecular classes of HCA.
Improving the Efficacy of Conventional Therapy by Adding Andrographolide Sulfonate in the Treatment of Severe Hand, Foot, and Mouth Disease: A Randomized Controlled Trial
Authors: Li Xiuhui , Zhang Chi , Shi Qingsheng , Yang Tong , Zhu Qingxiong , Tian Yimei , Lu Cheng , Zhang Zhiying , Jiang Zhongsheng , Zhou Hongying , Wen Xiaofeng , Yang Huasheng , Ding Xiaorong , Liang Lanchun , Liu Yan , Wang Yongyan , Lu Aiping
Published: January 2013

Background. Herb-derived compound andrographolide sulfonate (called Xiyanping injection) recommended control measure for severe hand, foot, and mouth disease (HFMD) by the Ministry of Health (China) during the 2010 epidemic. However, there is a lack of good quality evidence directly comparing the efficacy of Andrographolide Sulfonate combination therapy with conventional therapy.Methods. 230 patients were randomly assigned to 7–10 days of Andrographolide Sulfonate 5–10 mg/Kg/day and conventional therapy, or conventional therapy alone.Results. The major complications occurred less often after Andrographolide Sulfonate (2.6% versus 12.1%; risk difference [RD], 0.94; 95% CI, 0.28–1.61;P=0.006). Median fever clearance times were 96 hours (CI, 80 to 126) for conventional therapy recipients and 48 hours (CI, 36 to 54) for Andrographolide Sulfonate combination-treated patients (χ2=16.57,P<0.001). The two groups did not differ in terms of HFMD-cause mortality (P=1.00) and duration of hospitalization (P=0.70). There was one death in conventional therapy group. No important adverse event was found in Andrographolide Sulfonate combination therapy group.Conclusions. The addition of Andrographolide Sulfonate to conventional therapy reduced the occurrence of major complications, fever clearance time, and the healing time of typical skin or oral mucosa lesions in children with severe HFMD.
Lovastatin-Enriched Rice Straw Enhances Biomass Quality and Suppresses Ruminal Methanogenesis
Authors: Faseleh Jahromi Mohammad , Liang Juan Boo , Mohamad Rosfarizan , Goh Yong Meng , Shokryazdan Parisa , Ho Yin Wan
Published: January 2013

The primary objective of this study was to test the hypothesis that solid state fermentation (SSF) of agro-biomass (using rice straw as model); besides, breaking down its lignocellulose content to improve its nutritive values also produces lovastatin which could be used to suppress methanogenesis in the rumen ecosystem. Fermented rice straw (FRS) containing lovastatin after fermentation withAspergillus terreuswas used as substrate for growth study of rumen microorganisms usingin vitrogas production method. In the first experiment, the extract from the FRS (FRSE) which contained lovastatin was evaluated for its efficacy for reduction in methane (CH4) production, microbial population, and activity in the rumen fluid. FRSE reduced total gas and CH4productions (P<0.01). It also reduced (P<0.01) total methanogens population and increased the cellulolytic bacteria includingRuminococcus albus,Fibrobacter succinogenes(P<0.01), andRuminococcus flavefaciens(P<0.05). Similarly, FRS reduced total gas and CH4productions, methanogens population, but increasedin vitrodry mater digestibility compared to the non-fermented rice straw. Lovastatin in the FRSE and the FRS significantly increased the expression of HMG-CoA reductase gene that produces HMG-CoA reductase, a key enzyme for cell membrane production in methanogenic Archaea.
Infrared Transmission Characteristics and Laser Tissue Interaction of Albino Pigskin Using Pulsed NIR Laser Light
Authors: Abdussamad Abbas Hisham , Triplett Gregory E.
Published: January 2013

This work explores near infrared transmission through albino pigskin and determines controllable factors that influence transmission efficiency. Pigskin samples of varying thicknesses were irradiated using a 1440 nm near-infrared laser diode, where a photodetector was used to measure the transmitted power, and a two-dimensional real time surface temperature distribution was recorded using infrared thermography. Results demonstrate that this technique could potentially lead to a noninvasive approach for enhancing wound healing.
Classification of Finite Rings of Orderp6by Generators and Relations
Authors: Karimi Beiranvand P. , Beyranvand R. , Gholami M.
Published: January 2013

For any finite abelian group(R,+), we define a binary operation or “multiplication” onRand give necessary and sufficient conditions on this multiplication forRto extend to a ring. Then we show when two rings made on the same group are isomorphic. In particular, it is shown that there aren+1rings of orderpnwith characteristicpn, wherepis a prime number. Also, all finite rings of orderp6are described by generators and relations. Finally, we give an algorithm for the computation of all finite rings based on their additive group.
Urinary Eosinophil Protein X in Childhood Asthma: Relation with Changes in Disease Control and Eosinophilic Airway Inflammation
Authors: Nuijsink Marianne , Hop Wim C. J. , Sterk Peter J. , Duiverman Eric J. , De Jongste Johan C.
Published: January 2013

The aim of this study was to assess cross-sectional and longitudinal correlations between uEPX and other markers of asthma control and eosinophilic airway inflammation.Methods. We measured uEPX at baseline, after 1 year and after 2 years in 205 atopic asthmatic children using inhaled fluticasone. At the same time points, we assessed symptom scores (2 weeks diary card), lung function (forced expiratory volume in one second (FEV1)), airway hyperresponsiveness (AHR), and percentage eosinophils in induced sputum (% eos).Results. We found negative correlations between uEPX and FEV1at baseline (r=-0.18,P=0.01), after 1 year (r=-0.25,P<0.01) and after 2 years (r=-0.21,P=0.02). Within-patient changes of uEPX showed a negative association with FEV1changes (at 1 year:r=-0.24,P=0.01; at 2 years:r=-0.21,P=0.03). Within-patient changes from baseline of uEPX correlated with changes in % eos. No relations were found between uEPX and symptoms.Conclusion. In this population of children with atopic asthma, uEPX correlated with FEV1and % eos, and within-subjects changes in uEPX correlated with changes in FEV1and % eos. As the associations were weak and the scatter of uEPX wide, it seems unlikely that uEPX will be useful as a biomarker for monitoring asthma control in the individual child.
Profile of New Leprosy Cases Attending a South Indian Referral Hospital in 2011-2012
Authors: Bhat Ramesh Marne , Chaitra Prakash
Published: January 2013

Background. Leprosy, a disabling infectious disease, is a major public health problem in some regions, requiring knowledge of its epidemiological variations so that strategies for case detection and disease control can be subsidized.Objectives. This study aims to evaluate the clinical and epidemiological profiles of leprosy patients attending a referral hospital in South India between 2011 and 2012.Methods. Medical records of newly diagnosed leprosy cases between April 2011 and March 2012 were analysed at the Department of Dermatology, Venereology and Leprosy, Father Muller Medical College Hospital, Mangalore, India. Data were obtained using a specific questionnaire and entered into the database system.Results. Adult males outnumbered females in our study. Detection rate among women and children under 15 years seems to be on the rise. Multibacillary leprosy was more frequent among the new cases with borderline tuberculoid as the predominant type, although smear positivity was seen in less than half of these clinical multibacillary cases. A higher occurrence of lepra reactions, neuritis, and deformities at the time of diagnosis was observed.Conclusion. The results of this study point to a high circulation of lepra bacilli in the community in the “elimination era” and also highlight the need for early diagnosis and appropriate treatment at the field level to prevent spread of bacilli and development of disabilities.
Fishing-Injury-Related Flexor Tenosynovitis of the Hand: A Case Report and Review
Authors: Young-Afat Danny A. , Dayicioglu Deniz , Oeltjen John C. , Garrison Audene P.
Published: January 2013

Hand infections occurring after fishing and other marine-related activities may involve uncommon bacteria that are not susceptible to the conventional or empiric antibiotic therapy used to treat soft tissue infections. Therefore appropriate treatment is often delayed and could lead to severe hand damage. An illustrative case of fishing-related injury leading to complicated tenosynovitis and horseshoe abscess caused byMycobacterium marinumand its treatment course is outlined. Laceration of the skin during boating is fairly common. Because of the rarity of some of the bacteria, referrals to the appropriate specialist including hand surgeons and infectious disease specialists should occur in early stages.M. marinuminfections should always be considered in injuries related to seawater and fishing as this may lead to early appropriate treatment and prevent severe damage.
Effect of Liquid Ga on Metal Surfaces: Characterization of Morphology and Chemical Composition of Metals Heated in Liquid Ga
Authors: Lee Eun Je , Hur Min Goo , Son Jeong Mun , Park Jeong Hoon , Yang Seung Dae
Published: January 2013

This study investigates the effect of liquid gallium (Ga) on metal foils made of titanium (Ti), niobium (Nb), and molybdenum (Mo). The Ti, Nb, and Mo foils were heated in liquid Ga at 120°C for a maximum of two weeks. After heating, the changes in the morphology and the chemical composition of the metal foils were analyzed by using a field emission scanning electron microscope, energy‐dispersive X‐ray spectrometer, X‐ray diffractometer, and X‐ray photoelectron spectrometer. The results of the analysis indicated that the Nb foil showed the minimum adhesion of liquid Ga to the surface while the maximum amount of liquid Ga was observed to adhere to the Ti foil. In addition, the Nb foil was oxidized and the Mo foil was reduced during the heating process. Considering these effects, we conclude that Mo may be used as an alternative encapsulation material for Ga in addition to Nb, which is used as the conventional encapsulation material, due to its chemical resistance against oxidation in hot liquid Ga.
Macroprolactinemia in a Patient with Invasive Macroprolactinoma: A Case Report and Minireview
Authors: Elenkova Atanaska , Abadzhieva Zdravka , Genov Nikolai , Vasilev Vladimir , Kirilov Georgi , Zacharieva Sabina
Published: January 2013

Background. Macroprolactin, the high-molecular prolactin isoform, is considered to be an inactive in vivo product with extrapituitary origin. Patients with macroprolactinemia are usually asymptomatic, with negative pituitary imaging. Based on these data, most authors do not recommend treatment and long-term followup in subjects with macroprolactinemia. However, there is evidence for overlapping clinical features among subjects with hyperprolactinemia due to monomeric or “big big” PRL isoform.Case Presentation. We present a 35-year-old female patient with secondary amenorrhea, mild obesity, hirsutism, headache and blurred vision. Hormonal evaluation revealed an extreme hyperprolactinemia (PRL = 10 610 mIU/L) almost exclusively due to macroprolactin isoform (MPRL = 10 107 mIU/L; recovery after PEG precipitation 4.7%) and hypogonadotropic hypogonadism. An invasive pituitary macroadenoma was visualized on MRI, and cabergoline therapy was initiated. Disappearance of clinical signs and symptoms, normalization of gonadotropin levels, and restoration of regular ovulatory menstrual cycles after 1 year of treatment are arguments in favor of preserved-macroprolactin bioactivity in this case. The significant decrease in MPRL levels and tumor volume in response to dopamine agonist therapy is suggestive for the tumoral origin of this isoform.Conclusions. Although macroprolactinemia is considered to be a benign condition, pituitary imaging, dopamine agonist treatment, and prolonged followup should be recommended in some particular cases.
Development and Validation of an Online Program for Promoting Self-Management among Korean Patients with Chronic Hepatitis B
Authors: Yang Jinhyang
Published: January 2013

The hepatitis B virus is second only to tobacco as a known human carcinogen. However, chronic hepatitis B usually does not produce symptoms and people feel healthy even in the early stages of live cancer. Therefore, chronically infected people should perceive it as a serious health problem and move on to appropriate health behaviour. The purpose of this paper is to develop and validate an online program for promoting self-management among Korean patients with chronic hepatitis B. The online program was developed using a prototyping approach and system developing life cycle method, evaluated by users for their satisfaction with the website and experts for the quality of the site. To evaluate the application of the online program, knowledge and self-management compliance of the subjects were measured and compared before and after the application of the online program. There were statistically significant increases in knowledge and self-management compliance in the user group. An online program with high accessibility and applicability including information, motivation, and behavior skill factors can promote self-management of the patient with chronic hepatitis B. Findings from this study allow Korean patients with chronic hepatitis B to engage in proactive and effective health management in the community or clinical practice.
Pyranoanthocyanin Derived Pigments in Wine: Structure and Formation during Winemaking
Authors: Marquez Ana , Serratosa María P. , Merida Julieta
Published: January 2013

In recent years many studies have been carried out on new pigments derived from anthocyanins that appear in wine during processing and aging. This paper aims to summarize the latest research on these compounds, focusing on the structure and the formation process. The main pyranoanthocyanins are formed from the reaction between the anthocyanins and some metabolites released during the yeast fermentation: carboxypyranoanthocyanins or type A vitisins, formed upon the reaction between the enol form of the pyruvic acid and the anthocyanins; type B vitisins, formed by the cycloaddition of an acetaldehyde molecule on an anthocyanin; methylpyranoanthocyanins, resulted from the reaction between acetone and anthocyanins; pinotins resulted from the covalent reaction between the hydroxycinnamic acids and anthocyanins; and finally flavanyl‐pyranoanthocyanins. On the other hand, the second generation of compounds has also been reviewed, where the initial compound is a pyranoanthocyanin. This family includes oxovitisins, vinylpyranoanthocyanins, pyranoanthocyanins linked through a butadienylidene bridge, and pyranoanthocyanin dimers.
Using Aptamers for Cancer Biomarker Discovery
Authors: Chang Yun Min , Donovan Michael J. , Tan Weihong
Published: January 2013

Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment) SELEX and cell-based SELEX (cell-SELEX). Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.
On the Combined Application of Iatroscan TLC-FID and GC-FID to Identify Total, Neutral, and Polar Lipids and Their Fatty Acids Extracted from Foods
Authors: Sinanoglou Vassilia J. , Strati Irini F. , Bratakos Sotirios M. , Proestos Charalampos , Zoumpoulakis Panagiotis , Miniadis-Meimaroglou Sofia
Published: January 2013

An efficient separation and quantification of the individual neutral and polar lipid classes and their constituent fatty acids was achieved by the combination of two different detection techniques: Iatroscan TLC-FID and GC-FID. The solvent composition and ratio of development system, the sample size, the fidelity, and precision were tested in order to estimate the effectiveness of separation of individual neutral and polar lipid classes and the quantitative reproducibility of the Iatroscan TLC-FID technique. GC-FID method, with a high-quality capillary column, allowed sensitive and reproducible fatty acid qualitative and quantitative analyses, separation of fatty acid structural isomers (e.g., n-C16:0, iso-C16:0 and anteiso-C16:0), positional isomers (e.g., C18:1ω-9 and C18:1ω-7), geometrical isomers (cis-trans), and homologues (e.g., C16:0, C17:0, C18:0, etc.) in standards and complex lipid samples. Seventeen (17) lipid classes and fifty-two (52) saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids were identified and quantified, respectively, in samples of standard lipid and fatty acid mixtures, simulating the composition of natural lipids and their fatty acid methyl esters in common foods. The wide number of applications establishes this combination of Iatroscan TLC-FID and GC-FID methods as a powerful tool for lipid class and fatty acid analysis of any fat origin.
Diagnosis and Multimodality Management of Cushing’s Disease: A Practical Review
Authors: Zada Gabriel
Published: January 2013

Cushing’s Disease is caused by oversecretion of ACTH from a pituitary adenoma and results in subsequent elevations of systemic cortisol, ultimately contributing to reduced patient survival. The diagnosis of Cushing’s Disease frequently involves a stepwise approach including clinical, laboratory, neuroimaging, and sometimes interventional radiology techniques, often mandating multidisciplinary collaboration from numerous specialty practitioners. Pituitary microadenomas that do not appear on designated pituitary MRI or dynamic contrast protocols may pose a particularly challenging subset of this disease. The treatment of Cushing’s Disease typically involves transsphenoidal surgical resection of the pituitary adenoma as a first-line option, yet may require the addition of adjunctive measures such as stereotactic radiosurgery or medical management to achieve normalization of serum cortisol levels. Vigilant long-term serial endocrine monitoring of patients is imperative in order to detect any recurrence that may occur, even years following initial remission. In this paper, a stepwise approach to the diagnosis, and various management strategies and associated outcomes in patients with Cushing’s Disease are discussed.
Central Adiposity and Subclinical Cardiovascular Disease in Police Officers
Authors: Baughman Penelope , Fekedulegn Desta , Andrew Michael E. , Joseph Parveen Nedra , Dorn Joan M. , Violanti John M. , Burchfiel Cecil M.
Published: January 2013

Given the associations between obesity and cardiovascular disease (CVD), we evaluated a related but less well-established association between waist circumference and brachial artery reactivity (BAR), a functional measurement of subclinical CVD, where lower levels indicate dysfunction. Regression models examined trends in mean BAR across waist circumference tertiles in police officers, a high-stress occupational group with increased risk for CVD. Mean BAR decreased across increasing waist tertiles among men, but not women, and this association was stronger among officers who consumed more alcohol. Larger waist circumference may be associated with lower BAR, providing an opportunity for intervention prior to disease development.
Loop-Mediated Isothermal Amplification Assay for the Rapid Detection ofStaphylococcus aureus
Authors: Lim King Ting , Teh Cindy Shuan Ju , Thong Kwai Lin
Published: January 2013

Staphylococcus aureus, including methicillin-resistantS. aureus(MRSA), is an important human pathogen that produces a variety of toxins and causes a wide range of infections, including soft-tissue infections, bacteremia, and staphylococcal food poisoning. A loop-mediated isothermal amplification (LAMP) assay targeting thearcCgene ofS. aureuswas developed and evaluated with 119S. aureusand 25 non-S. aureusstrains. The usefulness of the assay was compared with the PCR method that targetsspaandarcCgenes. The optimal temperature for the LAMP assay was 58.5°C with a detection limit of 2.5 ng/μL and 102 CFU/mL when compared to 12.5 ng/μL and 103 CFU/mL for PCR (spaandarcC). Both LAMP and PCR assays were 100% specific, 100% sensitive, 100% positive predictive value (PPV), and 100% negative predictive value (NPV). When tested on 30 spiked blood specimens (21 MRSA, eight non-S. aureusand one negative control), the performance of LAMP and PCR was comparable: 100% specific, 100% sensitive, 100% PPV, and 100% NPV. In conclusion, the LAMP assay was equally specific with a shorter detection time when compared to PCR in the identification ofS. aureus. The LAMP assay is a promising alternative method for the rapid identification ofS. aureusand could be used in resource-limited laboratories and fields.
Morphology-Controlled Synthesis and Characterization of Magnetic Iron Oxide Nanocrystals and Their Potential Applications in Selective Oxidation of Alcohols and Olefins
Authors: Banerjee Subhash , Santra Swadeshmukul
Published: January 2013

A protocol for the preparation of iron oxide nanocrystals of two different (nanorods and octahedrons) morphologies has been developed and the synthesized nanocrystals were well characterized by TEM and XRD. These two nanocrystals have been applied for the selectivie oxidation of aryl-methanol and vinyl-arene. Moreover, the magnetic catalysts have easily separated from reaction mixture by a magnet and are reused without appreciable loss of catalytic activity. The oxidation processes avoid the use of toxic catalysts and volatile and hazardous organic solvents.
FOXP3Regulates Sensitivity of Cancer Cells to Irradiation by Transcriptional Repression ofBRCA1
Authors: Li Weiquan , Katoh Hiroto , Wang Lizhong , Yu Xiaochun , Du Zhanwen , Yan Xiaoli , Zheng Pan , Liu Yang
Published: January 2013

FOXP3 is an X-linked tumor suppressor gene and a master regulator in T regulatory cell function. This gene has been found to be mutated frequently in breast and prostate cancers and to inhibit tumor cell growth, but its functional significance in DNA repair has not been studied. We found that FOXP3 silencing stimulates homologous recombination-mediated DNA repair and also repair of γ-irradiation-induced DNA damage. Expression profiling and chromatin-immunoprecipitation analyses revealed that FOXP3 regulated the BRCA1-mediated DNA repair program. Among 48 FOXP3-regulated DNA repair genes, BRCA1 and 12 others were direct targets of FOXP3 transcriptional control. Site-specific interaction of FOXP3 with the BRCA1 promoter repressed its transcription. Somatic FOXP3 mutants identified in breast cancer samples had reduced BRCA1 repressor activity, whereas FOXP3 silencing and knock-in of a prostate cancer-derived somatic FOXP3 mutant increased the radioresistance of cancer cells. Together our findings provide a missing link between FOXP3 function and DNA repair programs. Cancer Res; 73(7); 2170–80. ©2012 AACR.
IFN-γ–Mediated Downregulation of LXA4 Is Necessary for the Maintenance of Nonresolving Inflammation and Papilloma Persistence
Authors: Wang Chunhui , Xiao Mingjie , Liu Xiaoman , Ni Chen , Liu Jianhong , Erben Ulrike , Qin Zhihai
Published: January 2013

Nonresolving inflammation is a hallmark of many types of tumors and the molecular mechanisms maintaining this inflammation are still largely unknown. In a two-stage carcinogenesis model, we observed here that the lack of IFN-γ receptor or neutralization of IFN-γ accelerated spontaneous papilloma regression in mice. The impaired maintenance of local inflammation was associated with reduced IFN-γ and enhanced biosynthesis of proresolution lipid mediator lipoxin A4 (LXA4). Interestingly, blocking LXA4 eliminated the effect of anti-IFN-γ, whereas treatment of mice with a therapeutic dose of LXA4 accelerated papilloma regression in an IFN-γ–independent manner. These results link for the first time a cytokine-dependent maintenance of inflammation with a downregulated production of proresolution lipid mediators. Strategies promoting spontaneous resolution of chronic inflammation by blocking IFN-γ and/or increasing LXA4 may be useful for the treatment of inflammation-associated tumors. Cancer Res; 73(6); 1742–51. ©2012 AACR.
mTOR Complex 2 Is Involved in Regulation of Cbl-Dependent c-FLIP Degradation and Sensitivity of TRAIL-Induced Apoptosis
Authors: Zhao Liqun , Yue Ping , Khuri Fadlo R. , Sun Shi-Yong
Published: January 2013

The mTOR positively regulates cell proliferation and survival through forming 2 complexes with raptor (mTOR complex 1; mTORC1) or rictor (mTOR complex 2; mTORC2). Compared with the mTORC1, relatively little is known about the biologic functions of mTORC2. This study focuses on addressing whether mTORC2 regulates apoptosis, particularly induced by TRAIL (TNFSF10). Using the mTOR kinase inhibitor, PP242, as a research tool, we found that it synergized with TRAIL to augment apoptosis of cancer cells. PP242 reduced the abundance of the short form of c-FLIP (FLIPS, CFLARS) and survivin (BIRC5). Enforced expression of ectopic FLIPS, but not survivin, attenuated augmented apoptosis induced by PP242 plus TRAIL. Thus, it is FLIPS downregulation that contributes to synergistic induction of apoptosis by PP242 plus TRAIL. PP242 decreased FLIPS stability, increased FLIPS ubiquitination, and facilitated FLIPS degradation. Moreover, knockdown of the E3 ligase Cbl (CBL) abolished PP242-induced FLIPS reduction. Thus, PP242 induces Cbl-dependent degradation of FLIPS, leading to FLIPS downregulation. Consistently, knockdown of rictor or mTOR, but not raptor, mimicked PP242 in decreasing FLIPS levels and sensitizing cells to TRAIL. Rictor knockdown decreased FLIPS stability, whereas enforced expression of rictor stabilized FLIPS. Moreover, silencing of Cbl abrogated FLIPS reduction induced by rictor knockdown. Collectively we conclude that it is mTORC2 inhibition that results in FLIPS downregulation and subsequent sensitization of TRAIL-induced apoptosis. Our findings provide the first evidence showing that mTORC2 stabilizes FLIPS, hence connecting mTORC2 signaling to the regulation of death receptor-mediated apoptosis. Cancer Res; 73(6); 1946–57. ©2012 AACR.
Lack of Estrogen Receptor-α Is Associated with Epithelial–Mesenchymal Transition and PI3K Alterations in Endometrial Carcinoma
Authors: Wik Elisabeth , Ræder Maria B. , Krakstad Camilla , Trovik Jone , Birkeland Even , Hoivik Erling A. , Mjos Siv , Werner Henrica M.J. , Mannelqvist Monica , Stefansson Ingunn M. , Oyan Anne M. , Kalland Karl H. , Akslen Lars A. , Salvesen Helga B.
Published: January 2013

Purpose: We hypothesized that estrogen receptor-α (ER-α) status in endometrial carcinomas, associated with poor prognosis, is reflected in transcriptional signatures suggesting targets for new therapy.

Experimental Design: Endometrial carcinoma samples in a primary investigation cohort (n = 76) and three independent validation cohorts (n = 155/286/111) were analyzed through integrated molecular profiling. Biomarkers were assessed by immunohistochemistry (IHC), DNA oligonucleotide microarray, quantitative PCR (qPCR), single-nucleotide polymorphism (SNP) array, and Sanger sequencing in the cohorts, annotated for comprehensive histopathologic and clinical data, including follow-up.

Results: ER-α immunohistochemical staining was strongly associated with mRNA expression of the receptor gene (ESR1) and patient survival (both P < 0.001). ER-α negativity associated with activation of genes involved in Wnt-, Sonic Hedgehog-, and TGF-β signaling in the investigation cohort, indicating epithelial–mesenchymal transition (EMT). The association between low ER-α and EMT was validated in three independent datasets. Furthermore, phosphoinositide 3-kinase (PI3K) and mTOR inhibitors were among the top-ranked drug signatures negatively correlated with the ER-α–negative tumors. Low ER-α was significantly associated with PIK3CA amplifications but not mutations. Also, low ER-α was correlated to high expression of Stathmin, a marker associated with PTEN loss, and a high PI3K activation signature.

Conclusion: Lack of ER-α in endometrial cancer is associated with EMT and reduced survival. We present a rationale for investigating ER-α's potential to predict response to PI3K/mTOR inhibitors in clinical trials and also suggest EMT inhibitors to ER-α–negative endometrial carcinomas. Clin Cancer Res; 19(5); 1094–105. ©2012 AACR.
Disparities in Revascularization Rates After Acute Myocardial Infarction Between Aboriginal and Non-Aboriginal People in Australia
Authors: Randall Deborah A. , Jorm Louisa R. , Lujic Sanja , O’Loughlin Aiden J. , Eades Sandra J. , Leyland Alastair H.
Published: January 2013

Background—

This study examined revascularization rates after acute myocardial infarction (AMI) for Aboriginal and non-Aboriginal patients sequentially controlling for admitting hospital and risk factors.

Methods and Results—

Hospital data from the state of New South Wales, Australia (July 2000 through December 2008) were linked to mortality data (July 2000 through December 2009). The study sample were all people aged 25 to 84 years admitted to public hospitals with a diagnosis of AMI (n=59 282). Single level and multilevel Cox regression was used to estimate rates of revascularization within 30 days of admission. A third (32.9%) of Aboriginal AMI patients had a revascularization within 30 days compared with 39.7% non-Aboriginal patients. Aboriginal patients had a revascularization rate 37% lower than non-Aboriginal patients of the same age, sex, year of admission, and AMI type (adjusted hazard ratio, 0.63; 95% confidence interval, 0.57–0.70). Within the same hospital, however, Aboriginal patients had a revascularization rate 18% lower (adjusted hazard ratio, 0.82; 95% confidence interval, 0.74–0.91). Accounting for comorbidities, substance use and private health insurance further explained the disparity (adjusted hazard ratio, 0.96; 95% confidence interval, 0.87–1.07). Hospitals varied markedly in procedure rates, and this variation was associated with hospital size, remoteness, and catheterization laboratory facilities.

Conclusions—

Aboriginal Australians were less likely to have revascularization procedures after AMI than non-Aboriginal Australians, and this was largely explained by lower revascularization rates at the hospital of first admission for all patients admitted to smaller regional and rural hospitals, a higher comorbidity burden for Aboriginal people, and to a lesser extent a lower rate of private health insurance among Aboriginal patients.
Preterm Birth and Future Maternal Blood Pressure, Inflammation, and Intimal-medial Thickness
Authors: Catov Janet M. , Lewis Cora E. , Lee Minjae , Wellons Melissa F. , Gunderson Erica P.
Published: January 2013

Preterm birth (PTB, <37 weeks) may be a marker of endothelial dysfunction and a proinflammatory phenotype; both are risk factors for cardiovascular disease. We studied 916 women (46% black) with 1181 live births between enrollment in the Coronary Artery Risk Development in Young Adults study (age 18–30 years) and 20 years later. C-reactive protein was measured at years 7, 15, and 20. Interleukin-6 and carotid intima-media thickness, which incorporated the common carotid arteries, bifurcations, and internal carotid arteries, were measured at year 20. Blood pressure, lipids, anthropometrics, and pregnancy events were assessed at all visits. Change in risk factors and differences in inflammatory markers and intima-media thickness according to PTB were evaluated. Women with PTBs (n=226) had higher mean systolic blood pressures before pregnancy (106 versus 105 mm Hg, respectively;
P
=0.03). Systolic and diastolic blood pressure increased more rapidly over 20 years compared with women with term births (
P
<0.01 time interaction), even after removing women with self-reported hypertension in pregnancy. Women with PTB versus term births had similar mean intima-media thickness adjusted for age, body mass index, race, lifestyle, and cardiovascular risk factors. C-reactive protein and interleukin-6 did not differ according to PTB. Women with PTB, regardless of hypertension during pregnancy, had higher blood pressure after pregnancy compared with women with term births. In the United States, where rates of PTB are high and race disparities persist, PTB may identify women with higher blood pressure in the years after pregnancy.