bluuebunny/crossref_metadata_2025 huggingface dataset:
Dark energy from gravitational corrections
Authors: Abe Yugo , Horikoshi Masaatsu , Kawamura Yoshiharu
Published: March 2017

We study physics concerning the cosmological constant problem in the framework of effective field theory and suggest that a dominant part of dark energy can originate from gravitational corrections of vacuum energy, under the assumption that the classical gravitational fields do not couple to a large portion of the vacuum energy effectively, in spite of the coupling between graviton and matters at a microscopic level. Our speculation is excellent with terascale supersymmetry.
Analysis and design of the system of a total digital Si-gyroscope
Authors: Huang Fuxiang , Liang Yin
Published: March 2017

In order to get a thorough understanding of the total digital silicon micro-gyroscope, a novel system-level model with details of both the sense and circuit is presented in this paper. Unlike the traditional structures of the digital part of the digital gyroscope, a structure with programmable delay units (PDUs) instead of DPLLs gives a brief and robust character of the whole system. And the PDUs coordinating with the FIR filter could lead to a removal of the IF filters of the sigma–delta DAC for feedback, which saves a lot of consumption. Two MASH sigma–delta ADCs are designed to convert the output of the charge–voltage converters to digital signals, which also bring a better stability. The ADCs achieve an SNR of 102.5 dB with a 10 kHz bandwidth. The stabilization of the closed drive mode has also been analyzed including how the noise caused by the quantization of the digital circuit is affecting the stabilization of both the amplitude and frequency of the driving signals. In the end, a final result of simulation of the gyroscope shows the correctness and accuracy of the whole model of the gyroscope.
Spin polarization properties at the spinterface of thiophene/Fe(100): First principles calculations
Authors: Cai L. L. , Tian Y. L. , Yuan X. B. , Hu G. C. , Ren J. F.
Published: March 2017

Based on density functional theory (DFT), the spin polarization properties of a thiophene molecule which is adsorbed at Fe (100) surface are discussed. A variety of horizontal and vertical adsorption configurations as well as their influences on the spin density distributions are studied in detail. The spin polarization comes from the [Formula: see text]-[Formula: see text] orbital coupling between the thiophene molecule and the electrode, which leads to the molecules’ energy level shifting and the density of states (DOS) broadening, so the two spin states near the Fermi level are exchange split. It is also found that the interfacial spin polarization is different under different contact configurations, and the biggest one will be obtained when the S atom is directly placed above the Fe atom at the horizontal direction. On the other hand, interface spin inversion can be obtained by adjusting the adsorption position, which will be helpful to build spin sensors.
The angular electronic band structure and free particle model of aromatic molecules: High-frequency photon-induced ring current
Authors: Öncan Mehmet , Koç Fatih , Şahin Mehmet , Köksal Koray
Published: March 2017

This work introduces an analysis of the relationship of first-principles calculations based on DFT method with the results of free particle model for ring-shaped aromatic molecules. However, the main aim of the study is to reveal the angular electronic band structure of the ring-shaped molecules. As in the case of spherical molecules such as fullerene, it is possible to observe a parabolic dispersion of electronic states with the variation of angular quantum number in the planar ring-shaped molecules. This work also discusses the transition probabilities between the occupied and virtual states by analyzing the angular electronic band structure and the possibility of ring currents in the case of spin angular momentum (SAM) or orbital angular momentum (OAM) carrying light. Current study focuses on the benzene molecule to obtain its angular electronic band structure. The obtained electronic band structure can be considered as a useful tool to see the transition probabilities between the electronic states and possible contribution of the states to the ring currents. The photoinduced current due to the transfer of SAM into the benzene molecule has been investigated by using analytical calculations within the frame of time-dependent perturbation theory.
Enhancing Quality of Learning Experience Through Intelligent Agent in E-Learning
Authors: Bhattacharya S. , Chowdhury S. , Roy S.
Published: March 2017

In this paper an interactive recommending agent is proposed which helps an e-learner to enhance the quality of learning experience resulting in efficient achievement of learning objectives. The agent achieves this with the help of a fuzzy rule base working on a variety of learning materials and recommending the appropriate learning path through them. In a learner-centric environment the learning behaviour of a learner may vary to a great extent due to the characteristics of the learner and his environment. Students are often misled while choosing the appropriate path of web learning tools owing to non-availability of a human teacher/guide. By the response of a learner to different positive and negative motivation factors the proposed system employs a fuzzy machine that is fed with realization parameters e.g. Satisfied, Depressed etc. The fuzzy machine working on the paradigm of fuzzy inference system processes these realization parameters with the help of a fuzzy rule base to produce the crisp measures of the learner’s cognitive states in terms of Belief, Behaviour and Attitude. On the basis of these defuzzified crisp diagnostic parameters the proposed system will enhanced the quality of learning experience of an e-learner. To ensure this the system will provide more detailed discussion on the subject matter along with some additional learning tools. Learners often get confused to select the proper tools among various. Therefore the proposed system will also suggest most popular path among those learners with the same understanding. This recommendation comes from the analysis of data mining result. The system was tested with a wide variety of school-level students. The response obtained indicates that it is able to enhance the quality of learning experience through its recommendation.
Pelvic musculature of
Vectidraco daisymorrisae
and consequences for pterosaur locomotion
Authors: Frigot Rachel A.
Published: March 2017

The unique morphology of pterosaurs makes them a compelling group to study, but the lack of ready analogues or descendant clades presents problems when inferring their biology and ecology. In this paper, the extant phylogenetic bracket is used to reconstruct the musculature of the pterosaur
Vectidraco daisymorrisae
and a detailed comparison is made between the musculature of this taxon and other reconstructions in the literature.
M. iliofibularis
is reconstructed as originating upon the angular process of the posterior iliac process, putting it into a mechanically advantageous position as an abductor.
M. flexor tibialis internus
is reconstructed as greatly enlarged over the ancestral state, probably in response to the reduction of
M. caudofemoralis brevis
and the tail. This enlargement is considered to correspond to the increasing role of
M. flexor tibialis internus
as a hip retractor.
Automated Bug Finding in Video Games
Authors: Varvaressos Simon , Lavoie Kim , Gaboury Sébastien , Hallé Sylvain
Published: March 2017

Runtime verification is the process of observing a sequence of events generated by a running system and comparing it to some formal specification for potential violations. We show how the use of a runtime monitor can greatly speed up the testing phase of a video game under development by automating the detection of bugs when the game is being played. We take advantage of the fact that a video game, contrarily to generic software, follows a special structure that contains a “game loop.” This game loop can be used to centralize the instrumentation and generate events based on the game's internal state. We report on experiments made on a sample of six real-world video games of various genres and sizes by successfully instrumenting and efficiently monitoring various temporal properties over their execution, including actual bugs reported in the games' bug tracking database in the course of their development.
Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing’s syndrome
Authors: Kang Seol-Hee , Lee Hae-Ahm , Kim Mina , Lee Eunjo , Sohn Uy Dong , Kim Inkyeom
Published: March 2017

Cushing’s syndrome is caused by overproduction of the adrenocorticotropic hormone (ACTH), which stimulates the adrenal grand to make cortisol. Skeletal muscle wasting occurs in pathophysiological response to Cushing’s syndrome. The forkhead box (FOX) protein family has been implicated as a key regulator of muscle loss under conditions such as diabetes and sepsis. However, the mechanistic role of the FOXO family in ACTH-induced muscle atrophy is not understood. We hypothesized that FOXO3a plays a role in muscle atrophy through expression of the E3 ubiquitin ligases, muscle RING finger protein-1 (MuRF-1), and atrogin-1 in Cushing’s syndrome. For establishment of a Cushing’s syndrome animal model, Sprague-Dawley rats were implanted with osmotic minipumps containing ACTH (40 ng·kg−1·day−1). ACTH infusion significantly reduced muscle weight. In ACTH-infused rats, MuRF-1, atrogin-1, and FOXO3a were upregulated and the FOXO3a promoter was targeted by the glucocorticoid receptor (GR). Transcriptional activity and expression of FOXO3a were significantly decreased by the GR antagonist RU486. Treatment with RU486 reduced MuRF-1 and atrogin-1 expression in accordance with reduced enrichment of FOXO3a and Pol II on the promoters. Knockdown of FOXO3a prevented dexamethasone-induced MuRF-1 and atrogin-1 expression. These results indicate that FOXO3a plays a role in muscle atrophy through expression of MuRF-1 and atrogin-1 in Cushing’s syndrome.
Acute corneal epithelial debridement unmasks the corneal stromal nerve responses to ocular stimulation in rats: implications for abnormal sensations of the eye
Authors: Hirata Harumitsu , Mizerska Kamila , Dallacasagrande Valentina , Guaiquil Victor H. , Rosenblatt Mark I.
Published: March 2017

It is widely accepted that the mechanisms for transducing sensory information reside in the nerve terminals. Occasionally, however, studies have appeared demonstrating that similar mechanisms may exist in the axon to which these terminals are connected. We examined this issue in the cornea, where nerve terminals in the epithelial cell layers are easily accessible for debridement, leaving the underlying stromal (axonal) nerves undisturbed. In isoflurane-anesthetized rats, we recorded extracellularly from single trigeminal ganglion neurons innervating the cornea that are excited by ocular dryness and cooling: low-threshold (<2°C cooling) and high-threshold (>2°C) cold-sensitive plus dry-sensitive neurons playing possible roles in tearing and ocular pain. We found that the responses in both types of neurons to dryness, wetness, and menthol stimuli were effectively abolished by the debridement, indicating that their transduction mechanisms lie in the nerve terminals. However, some responses to the cold, heat, and hyperosmolar stimuli in low-threshold cold-sensitive plus dry-sensitive neurons still remained. Surprisingly, the responses to heat in approximately half of the neurons were augmented after the debridement. We were also able to evoke these residual responses and follow the trajectory of the stromal nerves, which we subsequently confirmed histologically. The residual responses always disappeared when the stromal nerves were cut at the limbus, suggesting that the additional transduction mechanisms for these sensory modalities originated most likely in stromal nerves. The functional significance of these residual and enhanced responses from stromal nerves may be related to the abnormal sensations observed in ocular disease.

NEW & NOTEWORTHY In addition to the traditional view that the sensory transduction mechanisms exist in the nerve terminals, we report here that the proximal axons (stromal nerves in the cornea from which these nerve terminals originate) may also be capable of transducing sensory information. We arrived at this conclusion by removing the epithelial cell layers of the cornea in which the nerve terminals reside but leaving the underlying stromal nerves undisturbed.
Microinjection of kynurenic acid in the rostral nucleus of the tractus solitarius disrupts spatiotemporal aspects of mechanically induced tracheobronchial cough
Authors: Poliacek Ivan , Pitts Teresa , Rose Melanie J. , Davenport Paul W. , Simera Michal , Veternik Marcel , Kotmanova Zuzana , Bolser Donald C.
Published: March 2017

The importance of neurons in the nucleus of the solitary tract (NTS) in the production of coughing was tested by microinjections of the nonspecific glutamate receptor antagonist kynurenic acid (kyn; 100 mM in artificial cerebrospinal fluid) in 15 adult spontaneously breathing anesthetized cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airway. Electromyograms (EMG) were recorded from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles. Bilateral microinjections of kyn into the NTS rostral to obex [55 ± 4 nl total in 2 locations ( n = 6) or 110 ± 4 nl total in 4 locations ( n = 5)], primarily the ventrolateral subnucleus, reduced cough number and expiratory cough efforts (amplitudes of ABD EMG and maxima of esophageal pressure) compared with control. These microinjections also markedly prolonged the inspiratory phase, all cough-related EMG activation, and the total cough cycle duration as well as some other cough-related time intervals. In response to microinjections of kyn into the NTS rostral to the obex respiratory rate decreased, and there were increases in the durations of the inspiratory and postinspiratory phases and mean blood pressure. However, bilateral microinjections of kyn into the NTS caudal to obex as well as control vehicle microinjections in the NTS location rostral to obex had no effect on coughing or cardiorespiratory variables. These results are consistent with the existence of a critical component of the cough rhythmogenic circuit located in the rostral ventral and lateral NTS. Neuronal structures of the rostral NTS are significantly involved specifically in the regulation of cough magnitude and phase timing.

NEW & NOTEWORTHY The nucleus of the solitary tract contains significant neuronal structures responsible for control of 1) cough excitability, 2) motor drive during cough, 3) cough phase timing, and 4) cough rhythmicity. Significant elimination of neurons in the solitary tract nucleus results in cough apraxia (incomplete and/or disordered cough pattern). The mechanism of the cough impairment is different from that for the concomitant changes in breathing.
Research on the Plasma Anemometer Based on AC Glow Discharge
Authors: Yu Bing , Shen Enyu , Yuan Pei , Shen Huaxu
Published: March 2017

A new plasma anemometer based on AC glow discharge is designed in this article. Firstly, theoretical analysis of plasma anemometer working principle is introduced to prove the feasibility of the experimental measurement method. Then the experiments are carried out to study the effects of different parameters on the static discharge characteristics of the plasma anemometer system, by which the system optimization methods are obtained. Finally, several groups of appropriate parameters are selected to build the plasma anemometer system based on resistance capacitance coupling negative feedback AC glow discharge, and different airflow speeds are applied to obtain the achievable velocity measurement range. The results show that there is a linear relationship between airflow velocity and discharge current in an allowable error range, which can be applied for airflow velocity measurement. Negative feedback coupling module, which is composed of the coupling resistance and the coupling capacitance, has good effects on improving the system stability. The measurement range of the airflow velocity is significantly increased when the electrode gap is 3 mm, coupling resistance is 470 Ω, and coupling capacitance is 220 pF.
The Level of Knowledge of Parkinson’s Disease among Nonprofessional Caregivers in a Movement Disorders Center in Turkey
Authors: Gultekin Murat , Sarılar Ayse Caglar , Ekinci Ayten , Erturk Gozde , Mirza Meral
Published: March 2017

Introduction. Only a few studies have been conducted to determine the level of knowledge among caregivers about Parkinson’s disease (PD). The aim of the current study was to determine the knowledge of PD among caregivers at a movement disorder clinic in Turkey. Methods. We conducted a questionnaire based interview with the subjects in a tertiary care neurology facility in Turkey. The questions were divided into two parts covering the symptomatology and treatment of PD. A questionnaire consisting of 10 questions was applied to the subjects who had to mark the correct option in a stipulated time. Results. Eighty caregivers were included in the study. The caregivers’ mean age was 47.94 years (SD = 12.40). There were 47 female caregivers (58.8%). The most well-known question was that the number of drugs given to the patient may vary with time (76.3%), whereas “the benefit noted in the patient’s treatment decreases over time” was the least known question (11.3%). Discussion. This study is the first in our country and shows the necessity to increase the knowledge of PD among caregivers and the public. Education programs may have a positive role in imparting knowledge to the caregivers of PD patients.
Analysis of Spatiotemporal Evolution of Isolated Rainstorm Events in Huai River Basin, China
Authors: Liu Simin , Wang Hao , Yan Denghua , Ren Qingfu , Wang Duo , Gong Boya
Published: March 2017

Because of the impacts of extreme climate, the severity, areal extent, and frequency of rainstorm events are rapidly increasing, especially in the Huai River Basin of China. This article is based on hourly precipitation data of 229 meteorological stations from 1951 through 2012, combined with statistical and meteorological theory. We used the Mann-Kendall mutation test, movingt-test, and inverse distance weighting spatial interpolation to analyze the spatiotemporal evolution of precipitation, duration, intensity, and frequency of isolated rainstorm events under climate change. The main results are as follows: (1) isolated rainstorm events were obviously bimodal and their occurrence moved backward in time. Their average duration and time of maximum intensities changed dramatically, without a significant increasing trend. The period since the 2000s has seen an increase of rainstorms and their temporal regression across the entire basin. (2) The intensity of isolated rainstorm events in the study area decreased, but precipitation, its duration, areal extent, and frequency had increasing trends basin-wide. (3) Four rainstorm event indices were examined for the period of 1990–2000. Relative to the years before 2003, the average precipitation increased by 2.1%, the average total duration by 8.1%, and the average frequency of occurrence by 25.5%. All indices show smaller minimum and larger maximum values. Overall, the isolated rainstorm events tended to increase.
The Determinants of Leptin Levels in Diabetic and Nondiabetic Saudi Males
Authors: Al Sheikh Mona Hmoud
Published: March 2017

Objective. This study aimed to identify the main determinants of serum leptin levels. Methods. A sample of 113 Saudi adult males (55 diabetic and 58 nondiabetic) was selected according to the inclusion and exclusion criteria identified below. Blood samples were taken from participants after fasting for 12 hours. For diabetic patients, the insulin dose was given 12 hours before. In general, the study instrument consisted of blood biochemical tests. Metabolic parameters, glycosylated hemoglobin (HbA1c), low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, and triglyceride (TG), and adipokines, leptin, adiponectin, visfatin, and resistin, were measured. Multivariate model was utilized to identify the relationship between leptin levels and the independent variables. Results. When adjusted for resistin in the diabetic group, the results demonstrated a significant relationship between visfatin, LDL and TG, and leptin levels (p<0.05). However, when controlled for resistin, the effect of LDL and TG disappeared while that of visfatin stayed in the model. For the nondiabetic group, the results indicated a significant relationship between insulin, BMI, and leptin levels when adjusted for resistin (p<0.05). However, the effect of insulin disappeared when the model was controlled for resistin. The study results found no relationship between leptin and adiponectin levels in either the diabetic or nondiabetic group and whether adjusted or controlled for resistin. Conclusion. This study provided better understanding of the metabolism of leptin and unveiled the major determinants of leptin levels in diabetic and nondiabetic males. In conclusion, these results show that the association between leptin and metabolic parameters decreases with the progress of disease.
Urinary Lactate Dehydrogenase Activity and Its Isozyme Patterns in Kawasaki Disease
Authors: Kawamura Yoichi , Takeshita Seiichiro , Kanai Takashi , Takizawa Mari , Yoshida Yusuke , Tsujita Yuki , Nonoyama Shigeaki
Published: March 2017

Abnormal urinary findings, such as sterile pyuria, proteinuria, and microscopic hematuria, are often seen in the acute phase of Kawasaki disease (KD). We investigated the potential significance of urinary lactate dehydrogenase (U-LDH) activity and its isozyme patterns in KD. Total U-LDH activity and its isozymes (U-LDH1-5) levels were compared among 120 patients with KD, 18 patients with viral infection (VI), and 43 patients with upper urinary tract infection (UTI) and additionally compared between intravenous immunoglobulin (IVIG) responders (n=89) and nonresponders (n=31) with KD. Total U-LDH activity was higher in KD (35.4±4.8 IU/L,P<0.05) and UTI patients (66.0±8.0 IU/L,P<0.01) than in VI patients (17.0±6.2 IU/L). In the isozyme pattern analysis, KD patients had high levels of U-LDH1 and U-LDH2, while UTI patients had high levels of U-LDH3, U-LDH4, and U-LDH5. Furthermore, IVIG nonresponders of KD had significantly higher levels of total U-LDH activity (45.1±4.7 IU/L,P<0.05), especially U-LDH1 and U-LDH2 (P<0.05), than IVIG responders (32.0±2.8 IU/L). KD patients have increased levels of total U-LDH activity, especially U-LDH-1 and U-LDH2, indicating a unique pattern of U-LDH isozymes different from that in UTI patients.
Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin‐1 Signaling in Monocrotaline‐Induced Pulmonary Hypertension
Authors: Steven Sebastian , Oelze Matthias , Brandt Moritz , Ullmann Elisabeth , Kröller-Schön Swenja , Heeren Tjebo , Tran Lan P. , Daub Steffen , Dib Mobin , Stalleicken Dirk , Wenzel Philip , Münzel Thomas , Daiber Andreas
Published: March 2017

Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin‐1 signaling was increased in MCT40‐treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase‐1 (HO‐1). PETN therapy improved endothelium‐dependent relaxation in pulmonary arteries and inhibited endothelin‐1‐induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM‐1) in endothelial cells. Conclusion. MCT‐induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.
Long-Term Structural Modification of Water under Microwave Irradiation: Low-Frequency Raman Spectroscopic Measurements
Authors: Yakunov A. V. , Biliy M. M. , Naumenko A. P.
Published: March 2017

Raman scattering has been used to study the influence of 2.45 GHz microwave on the structure of water. It has been shown that treatment of the distilled water samples by electromagnetic field leads to long-term changes in the vibrational density of states. It was established that the retention time of structural changes of the water samples depends on the sample volume. The experimental results have been interpreted on the basis of the percolation model. It has been suggested that the change in the chemical composition of the water treated by microwaves can lead to a change in the structure of the percolation cluster formed by the network of hydrogen bonds. The time of the equilibrium structure recovery of the percolation cluster after termination of the microwaves depends on the cluster size and is much slower than the recovery in the chemical composition of water.
Forkhead Protein FoxO1 Acts as a Repressor to Inhibit Cell Differentiation in Human Fetal Pancreatic Progenitor Cells
Authors: Jiang Zongzhe , Tian Jingjing , Zhang Wenjian , Yan Hao , Liu Liping , Huang Zhenhe , Lou Jinning , Ma Xiaosong
Published: March 2017

Our colleagues have reported previously that human pancreatic progenitor cells can readily differentiate into insulin-containing cells. Particularly, transplantation of these cell clusters upon in vitro induction for 3-4 w partially restores hyperglycemia in diabetic nude mice. In this study, we used human fetal pancreatic progenitor cells to identify the forkhead protein FoxO1 as the key regulator for cell differentiation. Thus, induction of human fetal pancreatic progenitor cells for 1 week led to increase of the pancreatic β cell markers such as Ngn3, but decrease of stem cell markers including Oct4, Nanog, and CK19. Of note, FoxO1 knockdown or FoxO1 inhibitor significantly upregulated Ngn3 and insulin as well as the markers such as Glut2, Kir6.2, SUR1, and VDCC, which are designated for mature β cells. On the contrary, overexpression of FoxO1 suppressed the induction and reduced expression of these β cell markers. Taken together, these results suggest that FoxO1 may act as a repressor to inhibit cell differentiation in human fetal pancreatic progenitor cells.
Effects of Micron Fish Bone with Different Particle Size on the Properties of Silver Carp(Hypophthalmichthys molitrix)Surimi Gels
Authors: Yin Tao , Park Jae W. , Xiong Shanbai
Published: March 2017

Qualities of silver carp surimi (SCS) gels incorporated with micron fish bone of different particle size (22 to 0.12 μm) were evaluated. Textural values, whiteness, and water holding capacity of the SCS gels with setting significantly increased (P<0.05) as the micron fish bone particle size decreased. As the particle size decreased, more calcium ion was apparently released from the fish bone (P<0.05). Consequently the released calcium ion increased the activity of endogenous transglutaminase (TGase) and resulted in the formation of more myosin heavy chain (MHC) cross-links in the SCS gel with setting. Fish bone with particle size below 0.48 μm was steadily trapped in the three-dimensional SCS gel network without disrupting the matrices. Results indicated that size reduction of the incorporated micron fish bone improved qualities of the SCS gel with setting by the means of releasing more calcium ion and maintaining better gel matrices.
Sparse Multipath Channel Estimation Using Norm Combination Constrained Set-Membership NLMS Algorithms
Authors: Wang Yanyan , Li Yingsong
Published: March 2017

A norm combination penalized set-membership NLMS algorithm withl0andl1independently constrained, which is denoted asl0andl1independently constrained set-membership (SM) NLMS (L0L1SM-NLMS) algorithm, is presented for sparse adaptive multipath channel estimations. The L0L1SM-NLMS algorithm with fast convergence and small estimation error is implemented by independently exerting penalties on the channel coefficients via controlling the large group and small group channel coefficients which are implemented byl0andl1norm constraints, respectively. Additionally, a further improved L0L1SM-NLMS algorithm denoted as reweighted L0L1SM-NLMS (RL0L1SM-NLMS) algorithm is presented via integrating a reweighting factor into our L0L1SM-NLMS algorithm to properly adjust the zero-attracting capabilities. Our developed RL0L1SM-NLMS algorithm provides a better estimation behavior than the presented L0L1SM-NLMS algorithm for implementing an estimation on sparse channels. The estimation performance of the L0L1SM-NLMS and RL0L1SM-NLMS algorithms is obtained for estimating sparse channels. The achieved simulation results show that our L0L1SM- and RL0L1SM-NLMS algorithms are superior to the traditional LMS, NLMS, SM-NLMS, ZA-LMS, RZA-LMS, and ZA-, RZA-, ZASM-, and RZASM-NLMS algorithms in terms of the convergence speed and steady-state performance.
Distribution of Neuroendocrine Cells in the Transition Zone of the Prostate
Authors: Kyoda Yuki , Ichihara Koji , Hashimoto Kohei , Kobayashi Ko , Fukuta Fumimasa , Masumori Naoya
Published: March 2017

Objectives. To evaluate the distribution of neuroendocrine (NE) cells which may influence the development of benign prostatic hyperplasia (BPH) in the transition zone (TZ).Methods. We reviewed specimens from 80 patients who underwent radical prostatectomy in our institution and evaluated the density of NE cells in the TZ. They were histologically classified into 3 groups: those with no adenomatous nodule in the TZ (group A), those with small nodules with normal epithelium and stroma around them in the TZ (group B), and those with large nodules occupying the TZ (group C). In the patients of group B, intra-adenoma (adenomatous nodules) and extra-adenoma (normal tissue) NE cells in the TZ were separately counted.Results. There were 22, 23, and 35 patients in groups A, B, and C, respectively. The median density of NE cells in the TZ of group B patients, 2.80/mm2, was significantly higher than that of NE cells in group A, 1.43/mm2, and group C, 0.61/mm2(p<0.001). In group B, the median density of extra-adenoma NE cells was significantly higher than that of intra-adenoma.Conclusions. Many NE cells exist around small adenoma in the TZ. NE cells may influence the initial growth of BPH in a paracrine fashion.Trial Registration. This study approved by our institutional review board was retrospectively registered (#272-14).
Comparative Evaluation of Anti-HER2 Affibody Molecules Labeled with 64Cu Using NOTA and NODAGA
Authors: Tolmachev Vladimir , Yim Cheng-Bin , Rajander Johan , Perols Anna , Karlström Amelie Eriksson , Haaparanta-Solin Merja , Grönroos Tove J. , Solin Olof , Orlova Anna
Published: March 2017

Imaging using affibody molecules enables discrimination between breast cancer metastases with high and low expression of HER2, making appropriate therapy selection possible. This study aimed to evaluate if the longer half-life of 64Cu (T1/2 = 12.7 h) would make 64Cu a superior nuclide compared to 68Ga for PET imaging of HER2 expression using affibody molecules. The synthetic ZHER2:S1 affibody molecule was conjugated with the chelators NOTA or NODAGA and labeled with 64Cu. The tumor-targeting properties of 64Cu-NOTA-ZHER2:S1 and 64Cu-NODAGA-ZHER2:S1 were evaluated and compared with the targeting properties of 68Ga-NODAGA-ZHER2:S1 in mice. Both 64Cu-NOTA-ZHER2:S1 and 64Cu-NODAGA-ZHER2:S1 demonstrated specific targeting of HER2-expressing xenografts. At 2 h after injection of 64Cu-NOTA-ZHER2:S1, 64Cu-NODAGA-ZHER2:S1, and 68Ga-NODAGA-ZHER2:S1, tumor uptakes did not differ significantly. Renal uptake of 64Cu-labeled conjugates was dramatically reduced at 6 and 24 h after injection. Notably, radioactivity uptake concomitantly increased in blood, lung, liver, spleen, and intestines, which resulted in decreased tumor-to-organ ratios compared to 2 h postinjection. Organ uptake was lower for 64Cu-NODAGA-ZHER2:S1. The most probable explanation for this biodistribution pattern was the release and redistribution of renal radiometabolites. In conclusion, monoamide derivatives of NOTA and NODAGA may be suboptimal chelators for radiocopper labeling of anti-HER2 affibody molecules and, possibly, other scaffold proteins with high renal uptake.
Thyroid Imaging Reporting and Data System Score Combined with the New Italian Classification for Thyroid Cytology Improves the Clinical Management of Indeterminate Nodules
Authors: Ulisse Salvatore , Bosco Daniela , Nardi Francesco , Nesca Angela , D’Armiento Eleonora , Guglielmino Valeria , De Vito Corrado , Sorrenti Salvatore , Pironi Daniele , Tartaglia Francesco , Arcieri Stefano , Catania Antonio , Monti Massimo , Filippini Angelo , Ascoli Valeria
Published: March 2017

The new Italian cytological classification (2014) of thyroid nodules replaced the TIR3 category of the old classification (2007) with two subclasses, TIR3A and TIR3B, with the aim of reducing the rate of surgery for benign diseases. Moreover, thyroid imaging reporting and data system (TI-RADS) score appears to ameliorate the stratification of the malignancy risk. We evaluated whether the new Italian classification has improved diagnostic accuracy and whether its association with TI-RADS score could improve malignancy prediction. We retrospectively analyzed 70 nodules from 70 patients classified as TIR3 according to the old Italian classification who underwent surgery for histological diagnosis. Of these, 51 were available for cytological revision according to the new Italian cytological classification. Risk of malignancy was determined for TIR3A and TIR3B, TI-RADS score, and their combination. A different rate of malignancy (p=0.0286) between TIR3A (13.04%) and TIR3B (44.44%) was observed. Also TI-RADS score is significantly (p=0.003) associated with malignancy. By combining cytology and TI-RADS score, patients could be divided into three groups with low (8.3%), intermediate (21.4%), and high (80%) risk of malignancy. In conclusion, the new Italian cytological classification has an improved diagnostic accuracy. Interestingly, the combination of cytology and TI-RADS score offers a better stratification of the malignancy risk.
Correlation Between Isocitrate Dehydrogenase Gene Aberrations and Prognosis of Patients with Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis
Authors: Xu Qingyu , Li Yan , Lv Na , Jing Yu , Xu Yihan , Li Yuyan , Li Wenjun , Yao Zilong , Chen Xiaosu , Huang Sai , Wang Lili , Li Yonghui , Yu Li
Published: March 2017

Purpose: Whether isocitrate dehydrogenase (IDH) gene aberrations affected prognosis of patients with acute myeloid leukemia (AML) was controversial. Here, we conducted a meta-analysis to evaluate their prognostic value.

Experimental Design: PubMed, Embase, Cochrane, and Chinese databases were searched to identify studies exploring how IDH gene aberrations affected AML outcome. Pooled HRs and relative risks (RR) were calculated, along with 95% confidence intervals (CI).

Results: Thirty-three reports were included. IDH mutations seemed not to affect overall survival (OS: HR, 1.05; 95% CI, 0.89–1.23) and event-free survival (EFS: HR, 0.97; 95% CI, 0.80–1.18) when considered as a single factor, but improved accumulative incidence of relapse (CIR: HR, 1.44; 95% CI, 1.18–1.76) in patients with intermediate-risk karyotypes (IR-AML). However, IDH1 mutation conferred worse OS (HR, 1.17; 95% CI, 1.05–1.31) and EFS (HR, 1.29; 95% CI, 1.07–1.56), especially in patients with normal cytogenetics (OS: HR, 1.21; 95% CI, 1.01–1.46; EFS: HR, 1.56; 95% CI, 1.23–1.98). Prognosis of the IDH1 single-nucleotide polymorphism rs11554137 was also poor (OS: HR, 1.34; 95% CI, 1.03–1.75). IDH2 mutation improved OS (HR, 0.78; 95% CI, 0.66–0.93), particularly in IR-AML patients (OS: HR, 0.65; 95% CI, 0.49–0.86). The IDH2 (R140) mutation was associated with better OS among younger cases (HR, 0.64; 95% CI, 0.49–0.82). Treatment outcome was poor [RR for complete remission rates in IDH1 mutation: 1.21; 95% CI, 1.02–1.44; IDH2 (R172) mutation: 2.14; 95% CI, 1.61–2.85].

Conclusions: Various subtypes of IDH mutations might contribute to different prognosis and be allowed to stratify IR-AML further. Clin Cancer Res; 23(15); 4511–22. ©2017 AACR.
Abstract A29: The mechanism of differential effect of metformin on colorectal cancer stem cells: Metabolic alteration via glutamine metabolic pathway
Authors: Lee Kyoung Jin , Kim Jae Hyun , Kwon Ji-Hee , Seo Yoo Jung , Kim Tae Il
Published: March 2017

Background/Aim: There have been reports about cancer stem cells (CSCs) suppressing effect of metformin in several cancers. However, the differential effect of metformin on CSCs and its mechanism has not been reported. We identified various effect of metformin in suppression of colorectal CSCs and its molecular mechanism in colorectal cancer (CRC) cell lines.

Methods: Eight CRC cell lines including HT29 and SW620 cells were used. The CSC suppressing effects of metformin (10 mM), glutaminase inhibitor (compound 968, 10 μM), and combination of two drugs were measured by flow cytometry (CD133/44), and tumor sphere formation assay. AMPK and mTOR signaling were examined by Western blotting using anti-pAMPK and anti-pS6, and oxygen consumption rate was measured. The CSC inhibitory effects were also evaluated in xenografted nude mice of HT19 and SW620 cells, using immunohistochemical stain for CD133/CD44.

Results: CSCs decreased after treatment of metformin in HT29, DLD-1, and LoVo, and HCT116 cells, but not in SW620, WiDr, Colo205, and Caco-2 cells. Treatment of metformin induced pAMPK activation and pS6 suppression in HT29 cells (metformin-sensitive cells), but not in SW620 cells (metformin-resistant cells). Oxygen consumption rate was higher in HT29 cells than in SW620 cells, and showed more prominent decrease after metformin treatment in HT29 cells. In addition, SW620 cells became sensitive to metformin in CSC-suppressing effect in glutamine-depleted media, but not in low glucose media. Considering the alternative energy source of glutamine, which escapes the effect of metformin on tumor cells, we found that combination of metformin and compound 968 induced CSC-suppressing effect in SW620 cells, and enhanced that effect in HT29 cells. Further, SW620 cells showed higher expression of glutaminase and glutamine transporter than HT29 cells. In xenograft model of HT29 and SW620 cells, combined treatment of metformin and 968 also showed the same results with in vitro experiments.

Conclusion: The effect of metformin on CSCs of CRC cells is various depending on AMPK-mTOR pathway and glutamine metabolic pathway. Inhibition of glutamine pathway could enhance the CSC-suppressing effect of metformin, overcoming metformin-resistance.

Citation Format: Kyoung Jin Lee, Jae Hyun Kim, Ji-Hee Kwon, Yoo Jung Seo, Tae Il Kim. The mechanism of differential effect of metformin on colorectal cancer stem cells: Metabolic alteration via glutamine metabolic pathway. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A29.
Abstract B02: Blood-based epigenetic profiling of circulating cell free nucleosomes in 2000 FIT positive individuals: A novel approach to colorectal cancer detection
Authors: Herzog Marielle , Eccleston Mark , Pamart Dorian , Cuvelier Brieuc , Christensen Ib Jarle , Nielson Hans Jørgen , Micallef Jake , Terrell Jason
Published: March 2017

Genome wide epigenetic signals are altered in cancer cells. In addition, circulating nucleosome bound DNA fragments contain the same mutations as matched cancer tissue samples suggesting a tumor origin for at least some circulating nucleosomes. We have developed ELISA tests for circulating nucleosomes (NuQ®) and show that the profile of epigenetic features, including histone modifications and variants, DNA modifications and adducts between nucleosomes and non-histone proteins can be correlated with clinical disease and overcomes a major limitation of simple nucleosome quantification for diagnostic and prognostic use.

Validation of this approach in a retrospective cohort of 4800 patients presenting with symptoms of Colorectal diseases generated a diagnostic NuQ® panel with sensitivity of 81% at a specificity of 80% in an age adjusted linear regression model for the detection of Colorectal cancer (CRC). In a subsequent pilot prospective study of 58 subjects, a sensitivity of 91% at 90% specificity was achieved for the detection of CRC.

We now present preliminary Nucleosomics® data from the first 2000 individuals of a 14 000 asymptomatic, average risk cohort as part of a prospective clinical comparison with a national Fecal Immunological Screening (FIT) program in Denmark. Successful validation of this approach would provide an affordable, accessible and easily implemented blood based testing alternative to address relatively low compliance of fecal testing.

Note: This abstract was not presented at the conference.

Citation Format: Marielle Herzog, Mark Eccleston, Dorian Pamart, Brieuc Cuvelier, Ib Jarle Christensen, Hans Jørgen Nielson, Jake Micallef, Jason Terrell. Blood-based epigenetic profiling of circulating cell free nucleosomes in 2000 FIT positive individuals: A novel approach to colorectal cancer detection. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B02.
Abstract IA03: Lessons from colorectal cancer
Authors: Kinzler Kenneth W.
Published: March 2017

Many of the fundamental tenets of cancer genetics have their origins in the study of colorectal cancer (CRC). This is, at least in part, due to several clinical features of CRC that make it a particularly attractive and amenable to study in humans. Some of these key features include the relative abundance of CRC and precursor adenomas in the general population, the ease of identifying and collecting adenomas through routine screening colonoscopies, the existence of well recognized histopathological classifications with defined clinical implications and the long standing description of several well defined inherited predispositions. As a result, studies in CRC have often proven to be seminal in defining the role of somatic mutations and germline variations in the initiation progression and resistance of human cancer. Moreover, studies of CRC have proven to be influential beyond the aforementioned areas helping to define the roles of diet, inflammation and the microbiome in human cancer and providing new paradigms for the prevention and management of cancer. How these findings inform our understanding of CRC and cancer in general will be discussed with special emphasis on emerging topics highlighted in this conference.

Citation Format: Kenneth W. Kinzler. Lessons from colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA03.
Abstract IA26: Changes in diet and microbiome that mitigate CRC risk in Native Africans vs. African Americans
Authors: O'Keefe Stephen J.
Published: March 2017

Colon cancer is an environmental disease associated with westernization, and it has been shown that it takes one generation for immigrants to change their risk of cancer. To investigate the role of the western diet in driving this change, we have switched the macronutrient composition of diets of groups of 20 healthy middle aged African Americans, who have the highest risk of colon cancer in the USA (~65:100,000) and rural Africans, who rarely get the disease (<5:100,000) and measured its impact on mucosal biomarkers of cancer risk and the colonic microbiota that we hypothesize regulate this risk. Twenty healthy middle-aged volunteers from each community were housed for two weeks so that food could be prepared and consumed under close supervision. Americans were given a “traditional African” diet, high in fiber and low in meat and fat, while Africans were given a western diet, high in meat and fat, low in fiber. Mucosal biopsies taken from the proximal, mid and distal colon at colonoscopy before and after the dietary switch showed significant suppression of inflammation and proliferation cancer biomarkers in Americans and increases in Africans. In keeping with our hypothesis, these changes were associated with changes in bacterial co-occurrences, notably those of butyrate producers, and their metabolomic phenotypes. Targeted analysis of microbes associated with saccharolytic fermentation and their products, short chain fatty acids, showed that they were strongly associated with suppression of cancer biomarkers, whilst microbes associated with bile acid deconjugation and secondary bile acid production exhibited the reverse, providing a mechanism for the strong epidemiological evidence that fiber reduces risk and fat, by increasing the hepatic synthesis of bile acids, increases risk. In conclusion, our results build on the observation that the incidence of colon cancer changes within one generation of westernization by showing that the mucosal changes associated with carcinogenesis change within two weeks of switching to a western diet and provide evidence that the change is mediated by colonic microbial metabolism.

Citation Format: Stephen J. O'Keefe. Changes in diet and microbiome that mitigate CRC risk in Native Africans vs. African Americans. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA26.