bluuebunny/crossref_metadata_2025 huggingface dataset:
React
Authors: CACM Staff
Published: December 2016

A discussion with Pete Hunt, Paul O'Shannessy, Dave Smith, and Terry Coatta
MicroRNA-125a-5p alleviates the deleterious effects of ox-LDL on multiple functions of human brain microvessel endothelial cells
Authors: Pan Qunwen , Liao Xiaorong , Liu Hua , Wang Yan , Chen Yanfang , Zhao Bin , Lazartigues Eric , Yang Yi , Ma Xiaotang
Published: December 2016

MicroRNA-125a-5p (miR-125a-5p) could participate in the pathogenesis of vascular diseases. In this study, we investigated the role of miR-125a-5p in oxidized low-density lipoprotein (ox-LDL)-induced functional changes in human brain microvessel endothelial cells (HBMEC). The reactive oxygen species (ROS) production, nitric oxide (NO) generation, senescence, apoptosis, and functions of HBMEC were analyzed. For mechanism study, the epidermal growth factor receptor (EGFR)/extracellular signal-regulated protein kinase (ERK)/p38 mitogen-activated protein kinase (p38 MAPK) pathway and phosphatidylinositol-3-kinase (PI3K)/serine/threonine kinase (Akt)/endothelial nitric oxide synthase (eNOS) pathway were analyzed. Results showed the following: 1) Expression of miR-125a-5p was reduced in ox-LDL-treated HBMEC. 2) Overexpression of miR-125a-5p protected HBMEC from ox-LDL-induced apoptosis, senescence, ROS production, and NO reduction. 3) Overexpression of miR-125a-5p increased HBMEC proliferation, migration, and tube formation, while decreasing HBMEC adhesion to leukocytes, as well as counteracting the effects of ox-LDL on those functions. 4) The levels of EGFR/ERK/p38 MAPK pathway, PI3K/Akt/eNOS pathway, cleaved caspase-3, and adherent molecular ICAM-1 and VCAM-1 were associated with the effects of ox-LDL on these HBMEC functions. In conclusion, miR-125a-5p could counteract the effects of ox-LDL on various HBMEC functions via regulating the EGFR/ERK/p38 MAPK and PI3K/Akt/eNOS pathways and cleaved caspase-3, ICAM-1, and VCAM-1 expression.
Sarcomeric protein modification during adrenergic stress enhances cross-bridge kinetics and cardiac output
Authors: Gresham Kenneth S. , Mamidi Ranganath , Li Jiayang , Kwak Hyerin , Stelzer Julian E.
Published: December 2016

Molecular adaptations to chronic neurohormonal stress, including sarcomeric protein cleavage and phosphorylation, provide a mechanism to increase ventricular contractility and enhance cardiac output, yet the link between sarcomeric protein modifications and changes in myocardial function remains unclear. To examine the effects of neurohormonal stress on posttranslational modifications of sarcomeric proteins, mice were administered combined α- and β-adrenergic receptor agonists (isoproterenol and phenylephrine, IPE) for 14 days using implantable osmotic pumps. In addition to significant cardiac hypertrophy and increased maximal ventricular pressure, IPE treatment accelerated pressure development and relaxation (74% increase in dP/d tmax and 14% decrease in τ), resulting in a 52% increase in cardiac output compared with saline (SAL)-treated mice. Accelerated pressure development was maintained when accounting for changes in heart rate and preload, suggesting that myocardial adaptations contribute to enhanced ventricular contractility. Ventricular myocardium isolated from IPE-treated mice displayed a significant reduction in troponin I (TnI) and myosin-binding protein C (MyBP-C) expression and a concomitant increase in the phosphorylation levels of the remaining TnI and MyBP-C protein compared with myocardium isolated from saline-treated control mice. Skinned myocardium isolated from IPE-treated mice displayed a significant acceleration in the rate of cross-bridge (XB) detachment (46% increase) and an enhanced magnitude of XB recruitment (43% increase) at submaximal Ca2+ activation compared with SAL-treated mice but unaltered myofilament Ca2+ sensitivity of force generation. These findings demonstrate that sarcomeric protein modifications during neurohormonal stress are molecular adaptations that enhance in vivo ventricular contractility through accelerated XB kinetics to increase cardiac output.

NEW & NOTEWORTHY Posttranslational modifications to sarcomeric regulatory proteins provide a mechanism to modulate cardiac function in response to stress. In this study, we demonstrate that neurohormonal stress produces modifications to myosin-binding protein C and troponin I, including a reduction in protein expression within the sarcomere and increased phosphorylation of the remaining protein, which serve to enhance cross-bridge kinetics and increase cardiac output. These findings highlight the importance of sarcomeric regulatory protein modifications in modulating ventricular function during cardiac stress.
Divergent outcomes of fructose consumption on exercise capacity of rats: friend or foe
Authors: Sun Angela , Huang An , Kertowidjojo Elizabeth , Song Su , Hintze Thomas H. , Sun Dong
Published: December 2016

To test the hypothesis that high fructose (HF) consumption divergently affects exercise capability as a function of feeding duration, rats were fed a normal (as control) diet or a normal caloric diet with HF for 3, 6, 10, and 30 days, respectively, and then were run on a treadmill. Results show that running distance and work were significantly increased, which was associated with greater exercise oxygen consumption in rats fed HF for 3 (HF-3D) and 6 days, but were decreased in rats fed HF for 30 days (HF-30D) compared with rats in their respective control groups. Shear stress-induced vasodilation (SSID) in isolated plantaris muscle arterioles was significantly greater in the HF-3D group than the control group. The difference in SSID between the two groups was abolished by Nω-nitro-l-arginine methyl ester (L-NAME), suggesting a nitric oxide (NO)-mediated response. Expression of phosphorylated/activated endothelial NO synthase (eNOS) and release of nitrite/NO were significantly increased in vessels of animals in the HF-3D group than controls. In contrast, arterioles isolated from the hypertensive rats in the HF-30D group displayed significantly attenuated NO-mediated SSID accompanied with greater production of superoxide compared with vessels of control animals. Additionally, the NO-dependent modulation of myocardial oxygen consumption (MV̇o2) was also impaired in the HF-30D group, and was prevented by blocking superoxide production with apocynin, an inhibitor that also normalized the reduced SSID in the HF-30D group. In conclusion, short-term (3–6 days) HF feeding enhances exercise potential via an increase in endothelial sensitivity to shear stress, which stimulates eNOS to release NO, leading to better tissue perfusion and utilization of oxygen. However, long-term (30 days) HF feeding initiates endothelial dysfunction by superoxide-dependent mechanisms to compromise exercise performance.

NEW & NOTEWORTHY The evidence that short-term fructose intake potentiates exercise capacity by nitric oxide-mediated mechanisms yields an optimal fructose feeding frame in which beneficial effects of fructose have been acquired while detrimental effects have not yet been manifested. This highlights the significance of exercise physiology in providing constructive regimens to improve physical performance.
The protective role of sex hormones in females and exercise prehabilitation in males on sternotomy-induced cranial hypoperfusion in aortic banded mini-swine
Authors: Olver T. Dylan , Hiemstra Jessica A. , Edwards Jenna C. , Ferguson Brian S. , Laughlin M. Harold , Emter Craig A.
Published: December 2016

During cardiac surgery, specifically sternotomy, cranial hypoperfusion is linked to cerebral ischemia, increased risk of perioperative watershed stroke, and other neurocognitive complications. The purpose of this study was to retrospectively examine the effect of sex hormones in females and exercise prehabilitation in males on median sternotomy-induced changes in cranial perfusion in a large animal model of heart failure. Cranial blood flow (CBF) before and 10 and 60 min poststernotomy was analyzed in eight groups of Yucatan mini-swine: female control, aortic banded, ovariectomized, and ovariectomized + aortic banded; male control, aortic banded, aortic banded + continuous exercise trained, and aortic banded + interval exercise trained. A median sternotomy decreased cranial perfusion during surgery in all pigs (~24 ± 2% relative to baseline; P ≤ 0.05). CBF was 30 ± 7% lower across all time points in all females vs. all males ( P ≤ 0.05) and sternotomy decreased cranial perfusion ( P ≤ 0.05) independent of sex (females = 34 ± 3% and males = 14 ± 3%) and aortic banding (intact control = 31 ± 5% and intact aortic banded = 31 ± 4%). CBF recovery at 60 min tended to be better in females vs. males (relative to 10 min poststernotomy, females = 23 ± 13% vs. males = −1 ± 5%) and intact aortic banded vs. control pigs (relative to 10 min poststernotomy, aortic banded = 43 ± 20% vs. control = 6 ± 16%; P ≤ 0.05) at 60 min poststernotomy. Ovariectomy impaired CBF recovery during cranial reperfusion 60 min following sternotomy (relative to baseline, all intact females = −1 ± 9% vs. all ovariectomized females = −15 ± 4%; P ≤ 0.05). Chronic exercise training completely prevented significant sternotomy-induced cranial hypoperfusion independent of aortic banding (sternotomy-induced deficit, all sedentary males = −24 ± 6% vs. all exercise-trained males = −7 ± 3%; P ≤ 0.05). Female sex hormones protected against impaired CBF recovery during reperfusion, while chronic exercise training prevented sternotomy-induced cranial hypoperfusion despite cardiac pressure overload.

NEW & NOTEWORTHY Our findings suggest a median sternotomy may predispose patients, possibly postmenopausal women and sedentary men, to perioperative cerebral ischemia, an increased risk of cardiac surgery-related stroke, and resulting neurocognitive impairments. Specifically, data from this common surgical procedure show: 1) median sternotomy independently decreases cranial perfusion; 2) female sex hormones improve cranial blood flow recovery following sternotomy; and 3) exercise prehabilitation prevents sternotomy-induced cranial hypoperfusion. Exercise prehabilitation before cardiac surgery may be advantageous for capable patients.
Automated classification of pain perception using high-density electroencephalography data
Authors: Misra Gaurav , Wang Wei-en , Archer Derek B. , Roy Arnab , Coombes Stephen A.
Published: December 2016

The translation of brief, millisecond-long pain-eliciting stimuli to the subjective perception of pain is associated with changes in theta, alpha, beta, and gamma oscillations over sensorimotor cortex. However, when a pain-eliciting stimulus continues for minutes, regions beyond the sensorimotor cortex, such as the prefrontal cortex, are also engaged. Abnormalities in prefrontal cortex have been associated with chronic pain states, but conventional, millisecond-long EEG paradigms do not engage prefrontal regions. In the current study, we collected high-density EEG data during an experimental paradigm in which subjects experienced a 4-s, low- or high-intensity pain-eliciting stimulus. EEG data were analyzed using independent component analyses, EEG source localization analyses, and measure projection analyses. We report three novel findings. First, an increase in pain perception was associated with an increase in gamma and theta power in a cortical region that included medial prefrontal cortex. Second, a decrease in lower beta power was associated with an increase in pain perception in a cortical region that included the contralateral sensorimotor cortex. Third, we used machine learning for automated classification of EEG data into low- and high-pain classes. Theta and gamma power in the medial prefrontal region and lower beta power in the contralateral sensorimotor region served as features for classification. We found a leave-one-out cross-validation accuracy of 89.58%. The development of biological markers for pain states continues to gain traction in the literature, and our findings provide new information that advances this body of work.

NEW & NOTEWORTHY The development of a biological marker for pain continues to gain traction in literature. Our findings show that high- and low-pain perception in human subjects can be classified with 89% accuracy using high-density EEG data from prefrontal cortex and contralateral sensorimotor cortex. Our approach represents a novel neurophysiological paradigm that advances the literature on biological markers for pain.
Investigation of Cognitive Improvement in Alcohol-Dependent Inpatients Using the Montreal Cognitive Assessment (MoCA) Score
Authors: Pelletier Stéphanie , Nalpas Bertrand , Alarcon Régis , Rigole Hélène , Perney Pascal
Published: December 2016

Background. Cognitive dysfunction is a common feature in alcohol use disorders. Its persistence following alcohol detoxification may impair quality of life and increase the risk of relapse. We analyzed cognitive impairment changes using the Montreal Cognitive Assessment (MoCA) score in a large sample of alcohol-dependent inpatients hospitalized for at least 4 weeks. Method. This was an observational longitudinal survey. Inclusion criteria were alcohol dependence (DSM-IV) and alcohol abstinence for at least one week. The MoCA test was administered on admission and at discharge. Results. 236 patients were included. The mean MoCA score significantly increased from 22.1±3.7 on admission to 25.11±3.12 at discharge. The corresponding effect-size of improvement was high, 1.1 [95% CI 1.0–1.2]. The degree of improvement was inversely correlated with the baseline MoCA score. The rate of high and normal, that is, >26, MoCA values increased from 15.8% on admission to 53.8% at discharge. MoCA score improvement was not correlated with the total length of abstinence prior to admission. Conclusion. The MoCA score seems to be a useful tool for measuring changes in cognitive performance in alcohol-dependent patients. A significant improvement in cognitive function was observed whatever the degree of impairment on admission and even after a long abstinence period.
Discrete PID-Type Iterative Learning Control for Mobile Robot
Authors: Wang Hongbin , Dong Jian , Wang Yueling
Published: December 2016

Through studying tracking problems of the wheeled mobile robot, this paper proposed a discrete iterative learning control approach based on PID with strong adaptability, fast convergence, and small error. This algorithm used discrete PID to filter rejection and restrained the influence of interference and noise on trajectory tracking, which made it more suitable for engineering application. The PID-type iterative learning convergence condition and certification procedure are presented. The results of simulation reveal that the PID-type ILC holds the features of simplicity, strong robustness, and high repeating precision and can well meet the control requirement of nonlinear discrete system.
Factors Associated with ICU Admission following Blunt Chest Trauma
Authors: Bellone Andrea , Bossi Ilaria , Etteri Massimiliano , Cantaluppi Francesca , Pina Paolo , Guanziroli Massimo , Bianchi AnnaMaria , Casazza Giovanni
Published: December 2016

Background. Blunt chest wall trauma accounts for over 10% of all trauma patients presenting to emergency departments worldwide. When the injury is not as severe, deciding which blunt chest wall trauma patients require a higher level of clinical input can be difficult. We hypothesized that patient factors, injury patterns, analgesia, postural condition, and positive airway pressure influence outcomes.Methods. The study population consisted of patients hospitalized with at least 3 rib fractures (RF) and at least one pulmonary contusion and/or at least one pneumothorax lower than 2 cm.Results. A total of 140 patients were retrospectively analyzed. Ten patients (7.1%) were admitted to intensive care unit (ICU) within the first 72 hours, because of deterioration of the clinical conditions and gas exchange with worsening of chest X-ray/thoracic ultrasound/chest computed tomography. On univariable analysis and multivariable analysis, obliged orthopnea (p=0.0018) and the severity of trauma score (p<0.0002) were associated with admission to ICU.Conclusions. Obliged orthopnea was an independent predictor of ICU admission among patients incurring non-life-threatening blunt chest wall trauma. The main therapeutic approach associated with improved outcome is the prevention of pulmonary infections due to reduced tidal volume, namely, upright postural condition and positive airway pressure.
Influence of Local Sand on the Physicomechanical Comportment and Durability of High Performance Concrete
Authors: Tebbal Nadia , Rahmouni Zine El Abidine
Published: December 2016

This research consists of incorporating the crushed sand (CS) in the composition of a concrete and studies the effect of its gradual replacement by the sand dune (SD) on sustainability of high performance concrete (HPC) in aggressive environments. The experimental study shows that the parameters of workability of HPC are improved when the CS is partially replaced by the SD (<2/3). However, a high content of SD (>1/3) additional quantities of water is needed to meet the workability properties. The mechanical strengths decrease by adding the SD to CS, but they reach acceptable values with CS in moderate dosages. The HPC performances are significantly better than the control concrete made up with the same aggregates. The specification tests of durability show that the water absorbing coefficients by capillarity increase after adding SD to the CS.
A Doubly Adaptive Algorithm for Edge Detection in 3D Images
Authors: Lantarón Sagrario , López M. Dolores , Rodrigo Javier
Published: December 2016

This paper proposes a new algorithm (DA3DED) for edge detection in 3D images. DA3DED is doubly adaptive because it is based on the adaptive algorithm EDAS-1 for detecting edges in functions of one variable and a second adaptive procedure based on the concept of projective complexity of a 3D image. DA3DED has been tested on 3D images that modelize real problems (composites and fractures). It has been much faster than the 1D edge detection algorithm for 3D images derived from EDAS-1.
Unbalanced Oxidant‐Antioxidant Status: A Potential Therapeutic Target for Coronary Chronic Total Occlusion in Very Old Patients
Authors: Li Xia , Hu Youdong , Zhang Fenglin , Chen Ying , Zhou Hualan , Guo Dianxuan , Zhao Qingna
Published: December 2016

Unbalanced oxidant and antioxidant status played an important role in myocardial infarction. The present study was a clinical trial combined preclinically with targeted agent against cardiovascular injuries and ischemia in vivo model. We tried to confirm the association of unbalanced oxidant and antioxidant status with coronary chronic total occlusion (CTO) in 399 very old patients (80~89 years) and investigated the potential therapeutic value of purified polysaccharide from endothelium corneum gigeriae galli (PECGGp). We analyzed levels of circulating superoxide dismutase 3 (SOD3), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), and malondialdehyde (MDA) in very old patients with coronary CTO. Levels of SOD3, NO, eNOS, and MDA in the cardiac tissue were measured in myocardial infarction rats. Levels of SOD3, eNOS, and NO were lowered (p < 0.001) and levels of MDA were increased (p < 0.001). PECGGp treatment increased levels of SOD3, eNOS, and NO (p < 0.01) in cardiac tissue, while decreasing levels of MDA (p < 0.01). PECGGp may suppress unbalanced oxidant and antioxidant status in infarcted myocardium by inhibiting levels of MDA and elevating NO, eNOS, and SOD3 levels. PECGGp could be considered as a potential therapeutic agent for coronary CTO in very old patients.
The Design Method of Axial Flow Runners Focusing on Axial Flow Velocity Uniformization and Its Application to an Ultra-Small Axial Flow Hydraulic Turbine
Authors: Nishi Yasuyuki , Kobayashi Yutaka , Inagaki Terumi , Kikuchi Norio
Published: December 2016

We proposed a portable and ultra-small axial flow hydraulic turbine that can generate electric power comparatively easily using the low head of open channels such as existing pipe conduits or small rivers. In addition, we proposed a simple design method for axial flow runners in combination with the conventional one-dimensional design method and the design method of axial flow velocity uniformization, with the support of three-dimensional flow analysis. Applying our design method to the runner of an ultra-small axial flow hydraulic turbine, the performance and internal flow of the designed runner were investigated using CFD analysis and experiment (performance test and PIV measurement). As a result, the runners designed with our design method were significantly improved in turbine efficiency compared to the original runner. Specifically, in the experiment, a new design of the runner achieved a turbine efficiency of 0.768. This reason was that the axial component of absolute velocity of the new design of the runner was relatively uniform at the runner outlet in comparison with that of the original runner, and as a result, the negative rotational flow was improved. Thus, the validity of our design method has been verified.
Ingestibility and Formulation Quality of Lansoprazole Orally Disintegrating Tablets
Authors: Chono Sumio , Matsui Megumi , Nakamura Katsuki , Kasai Ryoya
Published: December 2016

Objectives. We evaluated the ingestibility and formulation quality of one branded (formulation A) and five generic (formulations B, C, D, E, and F) lansoprazole orally disintegrating (OD) tablets. Methods. Ingestibility, including the oral disintegrating time, taste, mouth feeling, and palatability, was examined by sensory testing in healthy subjects. Formulation qualities, including salivary stability, gastric acid resistance, and intestinal dissolution behavior, were examined. Results and Discussion. The oral disintegration time of formulation F (52 s) was significantly longer than that of other formulations (32–37 s). More than 90% of subjects did not experience bitterness with formulations A, E, and F, whereas 50% of subjects felt rough and powdery sensations with formulations B, C, and D. More than 80% of subjects suggested that formulations A, E, and F had good palatability. Ingestibility was different between formulations. OD tablets consist of enteric granules containing lansoprazole, which is unstable in gastric acid. Enteric granules of each formulation were stable in artificial saliva and gastric juice. No differences were observed in dissolution behaviors among the formulations, indicating that the formulation quality of the formulations was almost equivalent. Conclusions. This study provides useful information for selecting branded or generic lansoprazole OD tablets for individualized treatments.
Nuclear Structure Calculations for Two-Neutrino Double-βDecay
Authors: Sarriguren P. , Moreno O. , de Guerra E. Moya
Published: December 2016

We study the two-neutrino double-βdecay in76Ge,116Cd,128Te,130Te, and150Nd, as well as the two Gamow-Teller branches that connect the double-βdecay partners with the states in the intermediate nuclei. We use a theoretical microscopic approach based on a deformed self-consistent mean field with Skyrme interactions including pairing and spin-isospin residual forces, which are treated in a proton-neutron quasiparticle random-phase approximation. We compare our results for Gamow-Teller strength distributions with experimental information obtained from charge-exchange reactions. We also compare our results for the two-neutrino double-βdecay nuclear matrix elements with those extracted from the measured half-lives. Both single-state and low-lying-state dominance hypotheses are analyzed theoretically and experimentally making use of recent data from charge-exchange reactions andβdecay of the intermediate nuclei.
Stationary Hand Gesture Authentication Using Edit Distance on Finger Pointing Direction Interval
Authors: Wong Alex Ming Hui , Kang Dae-Ki
Published: December 2016

One of the latest authentication methods is by discerning human gestures. Previous research has shown that different people can develop distinct gesture behaviours even when executing the same gesture. Hand gesture is one of the most commonly used gestures in both communication and authentication research since it requires less room to perform as compared to other bodily gestures. There are different types of hand gesture and they have been researched by many researchers, but stationary hand gesture has yet to be thoroughly explored. There are a number of disadvantages and flaws in general hand gesture authentication such as reliability, usability, and computational cost. Although stationary hand gesture is not able to solve all these problems, it still provides more benefits and advantages over other hand gesture authentication methods, such as making gesture into a motion flow instead of trivial image capturing, and requires less room to perform, less vision cue needed during performance, and so forth. In this paper, we introduce stationary hand gesture authentication by implementing edit distance on finger pointing direction interval (ED-FPDI) from hand gesture to model behaviour-based authentication system. The accuracy rate of the proposed ED-FPDI shows promising results.
Stabilized Polymer Micelles for the Development of IT-147, an Epothilone D Drug-Loaded Formulation
Authors: Carie Adam , Sullivan Bradford , Ellis Tyler , Semple J. Edward , Buley Taylor , Costich Tara Lee , Crouse Richard , Bakewell Suzanne , Sill Kevin
Published: December 2016

Epothilones have demonstrated promising potential for oncology applications but suffer from a narrow therapeutic window. Epothilone D stabilizes microtubules leading to apoptosis, is active against multidrug-resistant cells, and is efficacious in animal tumor models despite lack of stability in rodent plasma. Clinical development was terminated in phase II due to dose limiting toxicities near the efficacious dose. Taken together, this made epothilone D attractive for encapsulation in a stabilized polymer micelle for improved safety and efficacy. We have designed a library of triblock copolymers to develop IT-147, a lead formulation of epothilone D that extends plasma circulation for accumulation in the tumor environment, and potentially decrease systemic exposure to reduce dose limiting toxicities. The drug loading efficiency for IT-147 exceeds 90%, is 75 nm in diameter, and demonstrates pH-dependent release of epothilone D without chemical conjugation or enzymatic activation. Administration of IT-147 at 20 mg/kg increases exposure of epothilone D to the plasma compartment over 6-fold compared to free drug. At the same dose, 20 mg/kg epothilone D from IT-147 is considered the no observed adverse effect level (NOAEL) but is the maximum tolerated dose for free drug. Consequently, IT-147 is positioned to be a safer, more effective means to deliver epothilone D.
Light-Weight and Versatile Monitor for a Self-Adaptive Software Framework for IoT Systems
Authors: Kim Young-Joo , Seok Jong-Soo , Jung YungJoon , Ha Ok-Kyoon
Published: December 2016

Today, various Internet of Things (IoT) devices and applications are being developed. Such IoT devices have different hardware (HW) and software (SW) capabilities; therefore, most applications require customization when IoT devices are changed or new applications are created. However, the applications executed on these devices are not optimized for power and performance because IoT device systems do not provide suitable static and dynamic information about fast-changing system resources and applications. Therefore, this paper proposes a light-weight and versatile monitor for a self-adaptive software framework to automatically control system resources according to the system status. The monitor helps running applications guarantee low power consumption and high performance for an optimal environment. The proposed monitor has two components: a monitoring component, which provides real-time static and dynamic information about system resources and applications, and a controlling component, which supports real-time control of system resources. For the experimental verification, we created a video transport system based on IoT devices and measured the CPU utilization by dynamic voltage and frequency scaling (DVFS) for the monitor. The results demonstrate that, for up to 50 monitored processes, the monitor shows an average CPU utilization of approximately 4% in the three DVFS modes and demonstrates maximum optimization in the Performance mode of DVFS.
Effects of Thermal Radiation on Mixed Convection Flow of a Micropolar Fluid from an Unsteady Stretching Surface with Viscous Dissipation and Heat Generation/Absorption
Authors: Singh Khilap , Kumar Manoj
Published: December 2016

A numerical model is developed to examine the effects of thermal radiation on unsteady mixed convection flow of a viscous dissipating incompressible micropolar fluid adjacent to a heated vertical stretching surface in the presence of the buoyancy force and heat generation/absorption. The Rosseland approximation is used to describe the radiative heat flux in the energy equation. The model contains nonlinear coupled partial differential equations which have been converted into ordinary differential equation by using the similarity transformations. The dimensionless governing equations for this investigation are solved by Runge-Kutta-Fehlberg fourth fifth-order method with shooting technique. Numerical solutions are then obtained and investigated in detail for different interesting parameters such as the local skin-friction coefficient, wall couple stress, and Nusselt number as well as other parametric values such as the velocity, angular velocity, and temperature.
Theoretical Analysis of the Noise Power Ratio of Nonlinear Power Amplifiers
Authors: Kumar Rajendra
Published: December 2016

This paper presents a theoretical analysis and derives the amplifier output noise power spectral density result in a closed form when the input to the amplifier is a band limited Gaussian noise. From the computed power spectral density the NPR is evaluated by a simple subtraction. The method can be applied to any amplifier with known input-output characteristics. The method may be applied to analyze various other important characteristics of the nonlinear amplifier such as spectral regrowth that refers to the spreading of the signal bandwidth when a band limited signal is inputted to the nonlinear amplifier. The paper presents numerical results on the NPR as a function of the noise bandwidth, depth level of the notch, and the output power back-off obtained from the analysis presented in the paper.
Nodular Lymphocyte Predominant Hodgkin Lymphoma of the Thyroid
Authors: Tavares Bello Carlos , Cassis João , Simões Helder , Sequeira Duarte João
Published: December 2016

Thyroid lymphomas are rare clinical entities that may result from either the primary intrathyroid de novo or secondary thyroid gland involvement of a lymphoma. Among these, the Hodgkin’s subtype is quite uncommon, accounting for 0.6–5% of all thyroid malignancies. The authors report on a 76-year-old female presenting with a thyroid nodule that, upon surgical excision, was found to be a nodular lymphocyte predominant Hodgkin lymphoma of the thyroid. So far, thyroid involvement by this variant has never been reported. Upon reporting on this clinical case, the authors emphasize the difficulties usually found in establishing the diagnosis and in defining the best management strategy. A thorough review of the available literature is done.
High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance
Authors: Nakata Masanori , Zhang Boyang , Yang Yifei , Okada Takashi , Shintani Norihito , Hashimoto Hitoshi , Yada Toshihiko
Published: December 2016

Pituitary adenylate cyclase-activating polypeptide (PACAP) acts on multiple processes of glucose and energy metabolism. PACAP potentiates insulin action in adipocytes and insulin release from pancreaticβ-cells, thereby enhancing glucose tolerance. Contrary to these effects at organ levels, PACAP null mice exhibit hypersensitivity to insulin. However, this apparent discrepancy remains to be solved. We aimed to clarify the mechanism underlying the antidiabetic phenotype of PACAP null mice. Feeding with high-fat diet (HFD) impaired insulin sensitivity and glucose tolerance in wild type mice, whereas these changes were prevented in PACAP null mice. HFD also impaired insulin-induced Akt phosphorylation in the liver in wild type mice, but not in PACAP null mice. Using GeneFishing method, HFD increased the leukocyte common antigen-related (LAR) protein tyrosine phosphatase in the liver in wild type mice. Silencing of LAR restored the insulin signaling in the liver of HFD mice. Moreover, the increased LAR expression by HFD was prevented in PACAP null mice. HFD increased the expression of VPAC1 receptor (VPAC1-R), one of three PACAP receptors, in the liver of wild type mice. These data indicate that PACAP-VPAC1-R signaling induces LAR expression and insulin resistance in the liver of HFD mice. Antagonism of VPAC1-R may prevent progression of HFD-induced insulin resistance in the liver, providing a novel antidiabetic strategy.
Evaluation of T Cell Immunity against Human Cytomegalovirus: Impact on Patient Management and Risk Assessment of Vertical Transmission
Authors: Freer Giulia , Quaranta Paola , Pistello Mauro
Published: December 2016

Cytomegalovirus (CMV) is one of the most common infectious agents, infecting the general population at an early age without causing morbidity most of the time. However, on particular occasions, it may represent a serious risk, as active infection is associated with rejection and disease after solid organ transplantation or fetal transmission during pregnancy. Several methods for CMV diagnosis are available on the market, but because infection is so common, careful selection is needed to discriminate primary infection from reactivation. This review focuses on methods based on CMV-specific T cell reactivity to help monitor the consequences of CMV infection/reactivation in specific categories of patients. This review makes an attempt at discussing the pros and cons of the methods available.
Treating without Seeing: Pain Management Practice in a Thai Context
Authors: Chatchumni Manaporn , Namvongprom Ampaporn , Eriksson Henrik , Mazaheri Monir
Published: December 2016

Pain management is a core nursing function, and it plays a key role in postoperative care. It is important to understand the cultural context of nursing practices and how this affects effective pain management. The aim of this study was to describe the professional and cultural framework within which pain management is practiced on a Thai surgical ward. Spradley’s ethnographic methodology was used. Data were collected through 98.5 hours of field observations and interviews at a surgical ward in Thailand. Three themes were constructed that describe the way Thai nurses practiced pain management: (i) complex communications system to address pain and to respond to it, (ii) the essence of Thai-ness, and (iii) a passive approach to pain management. The results indicate that, in the response to discomfort and pain, better pain management will result if there is a shift from functional to patient-centered care. The nursing culture needs to be further researched and discussed, in order to set priorities in line with the goals of national and international organizations for improving postoperative care and promoting patient comfort.
Effect of Mass Proportion of Municipal Solid Waste Incinerator Bottom Ash Layer to Municipal Solid Waste Layer on the Cu and Zn Discharge from Landfill
Authors: Kong Qingna , Yao Jun , Qiu Zhanhong , Shen Dongsheng
Published: December 2016

Municipal solid waste incinerator (MSWI) bottom ash is often used as the protection layer for the geomembrane and intermediate layer in the landfill. In this study, three sets of simulated landfills with different mass proportion of MSWI bottom ash layer to municipal solid waste (MSW) layer were operated. Cu and Zn concentrations in the leachates and MSW were monitored to investigate the effect of MSWI bottom ash layer on the Cu and Zn discharge from the landfill. The results showed that the Zn discharge was dependent on the mass proportion of MSWI bottom ash layer. The pH of landfill was not notably increased when the mass proportion of MSWI bottom ash layer to MSW layer was 1 : 9, resulting in the enhancement of the Zn discharge. However, Zn discharge was mitigated when the mass proportion was 2 : 8, as the pH of landfill was notably promoted. The discharge of Cu was not dependent on the mass proportion, due to the great affinity of Cu to organic matter. Moreover, Cu and Zn contents of the sub-MSW layer increased due to the MSWI bottom ash layer. Therefore, the MSWI bottom ash layer can increase the potential environmental threat of the landfill.
Combined Inhibition of Both p110α and p110β Isoforms of Phosphatidylinositol 3-Kinase Is Required for Sustained Therapeutic Effect in PTEN-Deficient, ER+ Breast Cancer
Authors: Hosford Sarah R. , Dillon Lloye M. , Bouley Stephanie J. , Rosati Rachele , Yang Wei , Chen Vivian S. , Demidenko Eugene , Morra Rocco P. , Miller Todd W.
Published: December 2016

Purpose: Determine the roles of the PI3K isoforms p110α and p110β in PTEN-deficient, estrogen receptor α (ER)-positive breast cancer, and the therapeutic potential of isoform-selective inhibitors.

Experimental Design: Anti-estrogen-sensitive and -resistant PTEN-deficient, ER+ human breast cancer cell lines, and mice bearing anti-estrogen–resistant xenografts were treated with the anti-estrogen fulvestrant, the p110α inhibitor BYL719, the p110β inhibitor GSK2636771, or combinations. Temporal response to growth factor receptor–initiated signaling, growth, apoptosis, predictive biomarkers, and tumor volumes were measured.

Results: p110β primed cells for response to growth factor stimulation. Although p110β inhibition suppressed cell and tumor growth, dual targeting of p110α/β enhanced apoptosis and provided sustained tumor response. The growth of anti-estrogen–sensitive cells was inhibited by fulvestrant, but fulvestrant inconsistently provided additional therapeutic effects beyond PI3K inhibition alone. Treatment-induced decreases in phosphorylation of AKT and Rb were predictive of therapeutic response. Short-term drug treatment induced tumor cell apoptosis and proliferative arrest to induce tumor regression, whereas long-term treatment only suppressed proliferation to provide durable regression.

Conclusions: p110β is the dominant PI3K isoform in PTEN-deficient, ER+ breast cancer cells. Upon p110β inhibition, p110α did not induce significant reactivation of AKT, but combined targeting of p110α/β most effectively induced apoptosis in vitro and in vivo and provided durable tumor regression. Because apoptosis and tumor regression occurred early but not late in the treatment course, and proliferative arrest was maintained throughout treatment, p110α/β inhibitors may be considered short-term cytotoxic agents and long-term cytostatic agents. Clin Cancer Res; 23(11); 2795–805. ©2016 AACR.
Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers
Authors: Van Roosbroeck Katrien , Fanini Francesca , Setoyama Tetsuro , Ivan Cristina , Rodriguez-Aguayo Cristian , Fuentes-Mattei Enrique , Xiao Lianchun , Vannini Ivan , Redis Roxana S. , D'Abundo Lucilla , Zhang Xinna , Nicoloso Milena S. , Rossi Simona , Gonzalez-Villasana Vianey , Rupaimoole Rajesha , Ferracin Manuela , Morabito Fortunato , Neri Antonino , Ruvolo Peter P. , Ruvolo Vivian R. , Pecot Chad V. , Amadori Dino , Abruzzo Lynne , Calin Steliana , Wang Xuemei , You M. James , Ferrajoli Alessandra , Orlowski Robert , Plunkett William , Lichtenberg Tara M. , Davuluri Ramana V. , Berindan-Neagoe Ioana , Negrini Massimo , Wistuba Ignacio I. , Kantarjian Hagop M. , Sood Anil K. , Lopez-Berestein Gabriel , Keating Michael J. , Fabbri Muller , Calin George A.
Published: December 2016

Purpose: The oncogenic miR-155 is upregulated in many human cancers, and its expression is increased in more aggressive and therapy-resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors.

Experimental Design: We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an in vivo orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expression and the combination of miR-155 and TP53 expression with cancer survival, we studied 956 patients with lung cancer, chronic lymphocytic leukemia, and acute lymphoblastic leukemia.

Results: We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents in vitro, and that downregulation of miR-155 successfully resensitizes tumors to chemotherapy in vivo. We show that anti-miR-155-DOPC can be considered non-toxic in vivo. We further demonstrate that miR-155 and TP53 are linked in a negative feedback mechanism and that a combination of high expression of miR-155 and low expression of TP53 is significantly associated with shorter survival in lung cancer.

Conclusions: Our findings support the existence of an miR-155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcome drug resistance, an important cause of cancer-related death. Clin Cancer Res; 23(11); 2891–904. ©2016 AACR.
ADNP Is a Therapeutically Inducible Repressor of WNT Signaling in Colorectal Cancer
Authors: Blaj Cristina , Bringmann Agnes , Schmidt Eva Marina , Urbischek Manuela , Lamprecht Sebastian , Fröhlich Thomas , Arnold Georg J. , Krebs Stefan , Blum Helmut , Hermeking Heiko , Jung Andreas , Kirchner Thomas , Horst David
Published: December 2016

Purpose: Constitutively active WNT signaling is a hallmark of colorectal cancers and a driver of malignant tumor progression. Therapeutic targeting of WNT signaling is difficult due to high pathway complexity and its role in tissue homeostasis. Here, we identify the transcription factor ADNP as a pharmacologically inducible repressor of WNT signaling in colon cancer.

Experimental Design: We used transcriptomic, proteomic, and in situ analyses to identify ADNP expression in colorectal cancer and cell biology approaches to determine its function. We induced ADNP expression in colon cancer xenografts by low-dose ketamine in vivo. Clinical associations were determined in a cohort of 221 human colorectal cancer cases.

Results: ADNP was overexpressed in colon cancer cells with high WNT activity, where it acted as a WNT repressor. Silencing ADNP expression increased migration, invasion, and proliferation of colon cancer cells and accelerated tumor growth in xenografts in vivo. Treatment with subnarcotic doses of ketamine induced ADNP expression, significantly inhibited tumor growth, and prolonged survival of tumor-bearing animals. In human patients with colon cancer, high ADNP expression was linked to good prognosis.

Conclusions: Our findings indicate that ADNP is a tumor suppressor and promising prognostic marker, and that ketamine treatment with ADNP induction is a potential therapeutic approach that may add benefit to current treatment protocols for patients with colorectal cancer. Clin Cancer Res; 23(11); 2769–80. ©2016 AACR.
Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice
Authors: Zimmermann Maike , Wang Si-Si , Zhang Hongyong , Lin Tzu-yin , Malfatti Michael , Haack Kurt , Ognibene Ted , Yang Hongyuan , Airhart Susan , Turteltaub Kenneth W. , Cimino George D. , Tepper Clifford G. , Drakaki Alexandra , Chamie Karim , de Vere White Ralph , Pan Chong-xian , Henderson Paul T.
Published: December 2016

We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin–DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [14C]carboplatin or [14C]gemcitabine and the resulting drug–DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug–DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug–DNA adducts as predictive biomarkers. Mol Cancer Ther; 16(2); 376–87. ©2016 AACR.
HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues
Authors: Lin Xiaoyu , Huang Xiaoli , Uziel Tamar , Hessler Paul , Albert Daniel H. , Roberts-Rapp Lisa A. , McDaniel Keith F. , Kati Warren M. , Shen Yu
Published: December 2016

An increasing number of BET family protein inhibitors have recently entered clinical trials. It has been reported that attempts of monitoring target engagement of the BET bromodomain inhibitor OTX015 using literature-described putative pharmacodynamic markers, such as c-Myc, BRD2, etc., failed to detect pharmacodynamic marker responses in AML patients treated at active dose and those with clinical responses. Here, we report the identification and characterization of HEXIM1 and other genes as robust pharmacodynamic markers for BET inhibitors. Global gene expression profiling studies were carried out using cancer cells and surrogate tissues, such as whole blood and skin, to identify genes that are modulated by BET family proteins. Candidate markers were further characterized for concentration- and time-dependent responses to the BET inhibitor ABBV-075 in vitro and in vivo. HEXIM1 was found to be the only gene that exhibited robust and consistent modulation by BET inhibitors across multiple cancer indications and surrogate tissues. Markers such as SERPINI1, ZCCHC24, and ZMYND8 were modulated by ABBV-075 and other BET inhibitors across cancer cell lines and xenograft tumors but not in blood and skin. Significant downregulation of c-Myc, a well-publicized target of BET inhibitors, was largely restricted to hematologic cancer cell lines. Incorporating well-characterized pharmacodynamic markers, such as HEXIM1 and other genes described here, can provide a better understanding of potential efficacy and toxicity associated with inhibiting BET family proteins and informs early clinical decisions on BET inhibitor development programs. Mol Cancer Ther; 16(2); 388–96. ©2016 AACR.