bluuebunny/crossref_metadata_2025 huggingface dataset:
Redox Modulating NRF2: A Potential Mediator of Cancer Stem Cell Resistance
Authors: Ryoo In-geun , Lee Sang-hwan , Kwak Mi-Kyoung
Published: November 2015

Tumors contain a distinct small subpopulation of cells that possess stem cell‐like characteristics. These cells have been called cancer stem cells (CSCs) and are thought to be responsible for anticancer drug resistance and tumor relapse after therapy. Emerging evidence indicates that CSCs share many properties, such as self‐renewal and quiescence, with normal stem cells. In particular, CSCs and normal stem cells retain low levels of reactive oxygen species (ROS), which can contribute to stem cell maintenance and resistance to stressful tumor environments. Current literatures demonstrate that the activation of ataxia telangiectasia mutated (ATM) and forkhead box O3 (FoxO3) is associated with the maintenance of low ROS levels in normal stem cells such as hematopoietic stem cells. However, the importance of ROS signaling in CSC biology remains poorly understood. Recent studies demonstrate that nuclear factor‐erythroid 2‐related factor 2 (NRF2), a master regulator of the cellular antioxidant defense system, is involved in the maintenance of quiescence, survival, and stress resistance of CSCs. Here, we review the recent findings on the roles of NRF2 in maintenance of the redox state and multidrug resistance in CSCs, focusing on how NRF2‐mediated ROS modulation influences the growth and resistance of CSCs.
Participant Experiences in the Environmental Determinants of Diabetes in the Young Study: Common Reasons for Withdrawing
Authors: Lernmark Barbro , Lynch Kristian , Baxter Judith , Roth Roswith , Simell Tuula , Smith Laura , Swartling Ulrica , Johnson Suzanne Bennett , TEDDY Study Group
Published: November 2015

Background. To characterize participant reasons for withdrawing from a diabetes focused longitudinal clinical observational trial (TEDDY) during the first three study years.Methods. 8677 children were recruited into the TEDDY study. At participant withdrawal staff recorded any reason parents provided for withdrawal. Reasons were categorized into (1) family characteristics and (2) protocol reasons. Families who informed staff of their withdrawal were classified as active withdrawals (AW); families without a final contact were considered passive withdrawals (PW).Results. Withdrawal was highest during the first study year(n=1220). Most families were AW (n=1549; 73.4%). PW was more common in the United States (n=1001; 37.8%) and among young mothers(p=0.001). The most frequent protocol characteristic was blood draw (55%) and the most common family reason was not having enough time (66%). The blood draw was more common among female participants; being too busy was more common among males. Both reasons were associated with study satisfaction.Conclusions. Results suggest that, for families of children genetically at risk for diabetes, procedures that can be painful/frightening should be used with caution. Study procedures must also be considered for the demands placed on participants. Study satisfaction should be regularly assessed as an indicator of risk for withdrawal.
Visibility Enhancement of Scene Images Degraded by Foggy Weather Conditions with Deep Neural Networks
Authors: Hussain Farhan , Jeong Jechang
Published: November 2015

Nowadays many camera-based advanced driver assistance systems (ADAS) have been introduced to assist the drivers and ensure their safety under various driving conditions. One of the problems faced by drivers is the faded scene visibility and lower contrast while driving in foggy conditions. In this paper, we present a novel approach to provide a solution to this problem by employing deep neural networks. We assume that the fog in an image can be mathematically modeled by an unknown complex function and we utilize the deep neural network to approximate the corresponding mathematical model for the fog. The advantages of our technique are as follows: (i) its real-time operation and (ii) being based on minimal input, that is, a single image, and exhibiting robustness/generalization for various unseen image data. Experiments carried out on various synthetic images indicate that our proposed technique has the abilities to approximate the corresponding fog function reasonably and remove it for better visibility and safety.
The Relevance of Nrf2 Pathway and Autophagy in Pancreatic Cancer Cells upon Stimulation of Reactive Oxygen Species
Authors: Zhang Lun , Li Jiahui , Ma Jiguang , Chen Xin , Chen Ke , Jiang Zhengdong , Zong Liang , Yu Shuo , Li Xuqi , Xu Qinhong , Lei Jianjun , Duan Wanxing , Li Wei , Shan Tao , Ma Qingyong , Shen Xin
Published: November 2015

Nrf2 (NF‐E2‐related factor 2) pathway and autophagy both can respond to oxidative stress to promote cancer cells to survive in the tumor microenvironment. We, therefore, explored the relevance between Nrf2 pathway and autophagy in pancreatic cancer cells upon stimulation of reactive oxygen species (ROS). Pancreatic cancer cells were cultured under controlled ROS stressing condition or basal condition. Different inhibitors were used to prevent autophagy at particular stages. Nrf2 siRNA was used to inhibit Nrf2 pathway activation. Ad‐mRFP‐GFP‐LC3 infection was used to monitor autophagic flux. The result shows that a small amount of exogenous hydrogen peroxide (H2O2) can significantly improve the level of intracellular ROS. Moreover, our findings indicate that ROS promotes the activation of both Nrf2 pathway and autophagy in pancreatic cancer cells. Moreover, our data demonstrate that suppression of autophagic activity at particular stages results in an increased promotion of Nrf2 pathway activation upon ROS stimulation. Furthermore, we found that silencing of Nrf2 promotes autophagy upon ROS stimulation. In addition, Nrf2 interference effectively promotes autophagic flux upon ROS stimulation. In summary, our findings suggest that Nrf2 pathway and autophagy have a negative interaction with each other upon ROS stimulation.
Target Centroid Position Estimation of Phase-Path Volume Kalman Filtering
Authors: Hu Fengjun
Published: November 2015

For the problem of easily losing track target when obstacles appear in intelligent robot target tracking, this paper proposes a target tracking algorithm integrating reduced dimension optimal Kalman filtering algorithm based on phase-path volume integral with Camshift algorithm. After analyzing the defects of Camshift algorithm, compare the performance with the SIFT algorithm and Mean Shift algorithm, and Kalman filtering algorithm is used for fusion optimization aiming at the defects. Then aiming at the increasing amount of calculation in integrated algorithm, reduce dimension with the phase-path volume integral instead of the Gaussian integral in Kalman algorithm and reduce the number of sampling points in the filtering process without influencing the operational precision of the original algorithm. Finally set the target centroid position from the Camshift algorithm iteration as the observation value of the improved Kalman filtering algorithm to fix predictive value; thus to make optimal estimation of target centroid position and keep the target tracking so that the robot can understand the environmental scene and react in time correctly according to the changes. The experiments show that the improved algorithm proposed in this paper shows good performance in target tracking with obstructions and reduces the computational complexity of the algorithm through the dimension reduction.
Juglanthraquinone C Induces Intracellular ROS Increase and Apoptosis by Activating the Akt/Foxo Signal Pathway in HCC Cells
Authors: Hou Ya-Qin , Yao Yao , Bao Yong-Li , Song Zhen-Bo , Yang Cheng , Gao Xiu-Li , Zhang Wen-Jing , Sun Lu-Guo , Yu Chun-Lei , Huang Yan-Xin , Wang Guan-Nan , Li Yu-Xin
Published: November 2015

Juglanthraquinone C (JC), a naturally occurring anthraquinone extracted from Juglans mandshurica, could induce apoptosis of cancer cells. This study aims to investigate the detailed cytotoxicity mechanism of JC in HepG2 and BEL‐7402 cells. The Affymetrix HG‐U133 Plus 2.0 arrays were first used to analyze the mRNA expression exposed to JC or DMSO in HepG2 cells. Consistent with the previous results, the data indicated that JC could induce apoptosis and hyperactivated Akt. The Western blot analysis further revealed that Akt, a well‐known survival protein, was strongly activated in HepG2 and BEL‐7402 cells. Furthermore, an obvious inhibitory effect on JC‐induced apoptosis was observed when the Akt levels were decreased, while the overexpression of constitutively active mutant Akt greatly accelerated JC‐induced apoptosis. The subsequent results suggested that JC treatment suppressed nuclear localization and increased phosphorylated levels of Foxo3a, and the overexpression of Foxo3a abrogated JC‐induced apoptosis. Most importantly, the inactivation of Foxo3a induced by JC further led to an increase of intracellular ROS levels by suppressing ROS scavenging enzymes, and the antioxidant N‐acetyl‐L‐cysteine and catalase successfully decreased JC‐induced apoptosis. Collectively, this study demonstrated that JC induced the apoptosis of hepatocellular carcinoma (HCC) cells by activating Akt/Foxo signaling pathway and increasing intracellular ROS levels.
Relation between Endothelial Nitric Oxide Synthase Genotypes and Oxidative Stress Markers in Larynx Cancer
Authors: Yanar K. , Çakatay U. , Aydın S. , Verim A. , Atukeren P. , Özkan N. E. , Karatoprak K. , Cebe T. , Turan S. , Ozkök E. , Korkmaz G. , Cacına C. , Küçükhüseyin O. , Yaylım İ.
Published: November 2015

Nitric oxide synthase (eNOS/NOS3) is responsible for the endothelial synthesis of nitric oxide (NO•). G894T polymorphism leads to the amino acid substitution from Glu298Asp that causes lower NOS3 activity and basal NO• production in NOS3 894T (298Asp) allele carriers compared with the GG homozygotes. NO• acts as an antioxidant protecting against Fenton’s reaction which generates highly reactive hydroxyl radicals. Allelic variation of NOS3 may influence an individual’s risk of laryngeal cancer (LC). In the current study we have examined the possible relationship between NOS3 G894T genotypes and various systemic oxidative damage markers such as protein carbonyl, advanced oxidation protein products, Cu, Zn‐superoxide dismutase, thiol group fractions, and lipid hydroperoxides in LC patients. Genotyping was carried out by PCR‐RFLP. In LC patients with TT genotype, Cu, Zn‐superoxide dismutase activities and nonprotein thiol levels were significantly higher than the controls. In patients with GT and GG genotype, high levels of lipid hydroperoxides showed statistical significance when compared to controls. Our results indicate a potential relationship among G894T polymorphism of NOS3, and impaired redox homeostasis. Further studies are required to determine the role of NOS3 gene polymorphism and impaired plasma redox homeostasis.
Miniaturized Human Insertable Cardiac Monitoring System with Wireless Power Transmission Technique
Authors: Lee Jong-Ha
Published: November 2015

Prolonged monitoring is more likely to diagnose atrial fibrillation accurately than intermittent or short-term monitoring. In this study, an implantable electrocardiograph (ECG) sensor to monitor atrial fibrillation patients in real time was developed. The implantable sensor is composed of a micro controller unit, an analog-to-digital converter, a signal transmitter, an antenna, and two electrodes. The sensor detects ECG signals from the two electrodes and transmits these to an external receiver carried by the patient. Because the sensor continuously transmits signals, its battery consumption rate is extremely high; therefore, the sensor includes a wireless power transmission module that allows it to charge wirelessly from an external power source. The integrated sensor has the approximate dimensions 3 mm × 4 mm × 14 mm, which is small enough to be inserted into a patient without the need for major surgery. The signal and power transmission data sampling rate and frequency of the unit are 300 samples/s and 430 Hz, respectively. To validate the developed sensor, experiments were conducted on small animals.
Facial Feature Extraction Using Frequency Map Series in PCNN
Authors: Nie Rencan , Zhou Dongming , He Min , Jin Xin , Yu Jiefu
Published: November 2015

Pulse coupled neural network (PCNN) has been widely used in image processing. The 3D binary map series (BMS) generated by PCNN effectively describes image feature information such as edges and regional distribution, so BMS can be treated as the basis of extracting 1D oscillation time series (OTS) for an image. However, the traditional methods using BMS did not consider the correlation of the binary sequence in BMS and the space structure for every map. By further processing for BMS, a novel facial feature extraction method is proposed. Firstly, consider the correlation among maps in BMS; a method is put forward to transform BMS into frequency map series (FMS), and the method lessens the influence of noncontinuous feature regions in binary images on OTS-BMS. Then, by computing the 2D entropy for every map in FMS, the 3D FMS is transformed into 1D OTS (OTS-FMS), which has good geometry invariance for the facial image, and contains the space structure information of the image. Finally, by analyzing the OTS-FMS, the standard Euclidean distance is used to measure the distances for OTS-FMS. Experimental results verify the effectiveness of OTS-FMS in facial recognition, and it shows better recognition performance than other feature extraction methods.
Epigenetic Control of Haematopoietic Stem Cell Aging and Its Clinical Implications
Authors: Choudry Fizzah Aziz , Frontini Mattia
Published: November 2015

Aging, chronic inflammation, and environmental insults play an important role in a number of disease processes through alterations of the epigenome. In this review we explore how age‐related changes in the epigenetic landscape can affect heterogeneity within the haematopoietic stem cell (HSC) compartment and the deriving clinical implications.
Fibroblast Growth Factor‐9 Activates c‐Kit Progenitor Cells and Enhances Angiogenesis in the Infarcted Diabetic Heart
Authors: Singla Dinender , Wang Jing
Published: November 2015

We hypothesized that fibroblast growth factor‐9 (FGF‐9) would enhance angiogenesis via activating c‐kit positive stem cells in the infarcted nondiabetic and diabetic heart. In brief, animals were divided into three groups: Sham, MI, and MI+FGF‐9. Two weeks following MI or sham surgery, our data suggest that treatment with FGF‐9 significantly diminished vascular apoptosis compared to the MI group in both C57BL/6 and db/db mice (p < 0.05). Additionally, the number of c‐kit+ve/SM α‐actin+ve cells and c‐kit+ve/CD31+ve cells were greatly enhanced in the MI+FGF‐9 groups relative to the MI suggesting FGF‐9 enhances c‐Kit cell activation and their differentiation into vascular smooth muscle cells and endothelial cells, respectively (p < 0.05). Histology shows that the total number of vessels were quantified for all groups and our data suggest that the FGF‐9 treated groups had significantly more vessels than their MI counterparts (p < 0.05). Finally, echocardiographic data suggests a significant improvement in left ventricular output, as indicated by fractional shortening and ejection fraction in both nondiabetic and diabetic animals treated with FGF‐9 (p < 0.05). Overall, our data suggests FGF‐9 has the potential to attenuate vascular cell apoptosis, activate c‐Kit progenitor cells, and enhance angiogenesis and neovascularization in C57BL/6 and db/db mice leading to improved cardiac function.
Dynamic Proteomic Analysis of Pancreatic Mesenchyme Reveals Novel Factors That Enhance Human Embryonic Stem Cell to Pancreatic Cell Differentiation
Authors: Russ Holger A. , Landsman Limor , Moss Christopher L. , Higdon Roger , Greer Renee L. , Kaihara Kelly , Salamon Randy , Kolker Eugene , Hebrok Matthias
Published: November 2015

Current approaches in human embryonic stem cell (hESC) to pancreatic beta cell differentiation have largely been based on knowledge gained from developmental studies of the epithelial pancreas, while the potential roles of other supporting tissue compartments have not been fully explored. One such tissue is the pancreatic mesenchyme that supports epithelial organogenesis throughout embryogenesis. We hypothesized that detailed characterization of the pancreatic mesenchyme might result in the identification of novel factors not used in current differentiation protocols. Supplementing existing hESC differentiation conditions with such factors might create a more comprehensive simulation of normal development in cell culture. To validate our hypothesis, we took advantage of a novel transgenic mouse model to isolate the pancreatic mesenchyme at distinct embryonic and postnatal stages for subsequent proteomic analysis. Refined sample preparation and analysis conditions across four embryonic and prenatal time points resulted in the identification of 21,498 peptides with high‐confidence mapping to 1,502 proteins. Expression analysis of pancreata confirmed the presence of three potentially important factors in cell differentiation: Galectin‐1 (LGALS1), Neuroplastin (NPTN), and the Laminin α‐2 subunit (LAMA2). Two of the three factors (LGALS1 and LAMA2) increased expression of pancreatic progenitor transcript levels in a published hESC to beta cell differentiation protocol. In addition, LAMA2 partially blocks cell culture induced beta cell dedifferentiation. Summarily, we provide evidence that proteomic analysis of supporting tissues such as the pancreatic mesenchyme allows for the identification of potentially important factors guiding hESC to pancreas differentiation.
Demographical, Clinical, and Psychological Characteristics of Users and Nonusers of an Online Platform for T2DM Patients (e-VitaDM-3/ZODIAC-44)
Authors: Roelofsen Yvonne , van Vugt Michael , Hendriks Steven H. , van Hateren Kornelis J. J. , Groenier Klaas H. , Snoek Frank J. , Kleefstra Nanne , Huijsman Robbert , Bilo Henk J. G.
Published: November 2015

Background. Online platforms offer opportunities for support in changing lifestyle and taking responsibility for one’s health, but engaging patients with type 2 diabetes is challenging. Previous studies have shown that patients interested in platforms were more often male, younger, and higher educated. This study aims to investigate differences in clinical and psychological characteristics between users and nonusers of a newly developed platform.Methods. A prospective study started in the Drenthe region of Netherlands. Participants in the study concerning quality of care and quality of life were additionally invited to use the platform.Results. 633 patients were registered after they opted for platform use. Of these patients, 361 (57.0%) never logged on, 184 (29.1%) were labeled “curious” users, and 88 (13.9%) were identified as “active” users. Users had lower HbA1c levels and more often hypertension compared to nonusers, and reported higher quality of life, better well-being, lower diabetes-related distress, and better medication adherence.Discussion. Platform use was associated with more favorable clinical and psychological characteristics relative to nonuse. Those with greater severity of disease, lower mood, and progression of disease used the platform the least. Other approaches need to be developed to reach these patients. Furthermore, improving the platform could also help to reach them. This trial is registered with Clinicaltrials.govNCT01570140.
Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways
Authors: Tsai Hsiao-Ya , Lin Chih-Pei , Huang Po-Hsun , Li Szu-Yuan , Chen Jia-Shiong , Lin Feng-Yen , Chen Jaw-Wen , Lin Shing-Jong
Published: November 2015

Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients.
Adiponectin Isoforms and Leptin Impact on Rheumatoid Adipose Mesenchymal Stem Cells Function
Authors: Skalska Urszula , Kontny Ewa
Published: November 2015

Adiponectin and leptin have recently emerged as potential risk factors in rheumatoid arthritis (RA) pathogenesis. In this study we evaluated the effects of adiponectin and leptin on immunomodulatory function of adipose mesenchymal stem cells (ASCs) derived from infrapatellar fat pad of RA patients. ASCs were stimulated with leptin, low molecular weight (LMW) and high/middle molecular weight (HMW/MMW) adiponectin isoforms. The secretory activity of ASCs and their effect on rheumatoid synovial fibroblasts (RA‐FLS) and peripheral blood mononuclear cells (PBMCs) from healthy donors have been analysed. RA‐ASCs secreted spontaneously TGFβ, IL‐6, IL‐1Ra, PGE2, IL‐8, and VEGF. Secretion of all these factors was considerably upregulated by HMW/MMW adiponectin, but not by LMW adiponectin and leptin. Stimulation with HMW/MMW adiponectin partially abolished proproliferative effect of ASC‐derived soluble factors on RA‐FLS but did not affect IL‐6 secretion in FLS cultures. ASCs pretreated with HMW/MMW adiponectin maintained their anti‐inflammatory function towards PBMCs, which was manifested by moderate PBMCs proliferation inhibition and IL‐10 secretion induction. We have proved that HMW/MMW adiponectin stimulates secretory potential of rheumatoid ASCs but does not exert strong impact on ASCs function towards RA‐FLS and PBMCs.
Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results
Authors: Mut-Salud Nuria , Álvarez Pablo Juan , Garrido Jose Manuel , Carrasco Esther , Aránega Antonia , Rodríguez-Serrano Fernando
Published: November 2015

The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency.
Epigenetics and Shared Molecular Processes in the Regeneration of Complex Structures
Authors: Rouhana Labib , Tasaki Junichi
Published: November 2015

The ability to regenerate complex structures is broadly represented in both plant and animal kingdoms. Although regenerative abilities vary significantly amongst metazoans, cumulative studies have identified cellular events that are broadly observed during regenerative events. For example, structural damage is recognized and wound healing initiated upon injury, which is followed by programmed cell death in the vicinity of damaged tissue and a burst in proliferation of progenitor cells. Sustained proliferation and localization of progenitor cells to site of injury give rise to an assembly of differentiating cells known as the regeneration blastema, which fosters the development of new tissue. Finally, preexisting tissue rearranges and integrates with newly differentiated cells to restore proportionality and function. While heterogeneity exists in the basic processes displayed during regenerative events in different species—most notably the cellular source contributing to formation of new tissue—activation of conserved molecular pathways is imperative for proper regulation of cells during regeneration. Perhaps the most fundamental of such molecular processes entails chromatin rearrangements, which prime large changes in gene expression required for differentiation and/or dedifferentiation of progenitor cells. This review provides an overview of known contributions to regenerative processes by noncoding RNAs and chromatin‐modifying enzymes involved in epigenetic regulation.
Evaluation of a Novel Radar Based Scanning Method
Authors: Fritsche Paul , Wagner Bernardo
Published: November 2015

The following paper introduces a novel scanning method for mapping and localization purposes in mobile robotics. Our method is based on a rotating monostatic radar network, which determines the positions of objects around the scanner via a continuously running lateration algorithm. The estimation of surfaces with ultrawideband radar networks has been studied experimentally in lab environments, especially with lateration, envelopes of spheres, and SEABED algorithms. But we do not see a link to the field of mapping and localization of mobile robots, where laser scanners are dominating. Indeed, only few research groups use radars for mapping and localization, but their applied sensor principle is based on a rotating focused radar beam. Consequently, only 2D radar scanners are known inside the robotic world and methods for 3D scanning with radars need to be investigated. This paper will derive the theoretical background of the sensor principle, which is based on a radar network on a rotating joint, and discuss its erroneous influences. We were performing first scans of standard geometries and deriving a model in order to compare theoretical and experimental measurement results. Furthermore, we present first mapping approaches and a simulation of a scanner with multiple sensors.
A Tile-Based EGPU with a Fused Universal Processing Engine and Graphics Coprocessor Cluster
Authors: Wang Yang , Zhou Li , Sun Tao , Chen Yanhu , Wang Lei , Sun Shaotao
Published: November 2015

As various applied sensors have been integrated into embedded devices, the Embedded Graphics Processing Unit (EGPU) has assumed more processing tasks, which requires an EGPU with higher performance. A tile-based EGPU is proposed that can be used in both general-purpose computing and 3D graphics rendering. With fused, scalable, and hierarchical parallelism architecture, the EGPU has the ability to address nearly 100 million vertices or fragments and achieves 1 GFLOPS per second at a clock frequency of 200 MHz. A fused and scalable architecture, constituted by Universal Processing Engine (UPE) and Graphics Coprocessor Cluster (GCC), ensures that the EGPU can adapt to various graphic processing scenes and situations, achieving more efficient rendering. Moreover, hierarchical parallelism is implemented via the UPE. Additionally, tiling brings a significant reduction in both system memory bandwidth and power consumption. A 0.18 µm technology library is used for timing and power analysis. The area of the proposed EGPU is 6.5 mm∗6.5 mm, and its power consumption is approximately 349.318 mW. Experimental results demonstrate that the proposed EGPU can be used in a System on Chip (SoC) configuration connected to sensors to accelerate its processing and create a proper balance between performance and cost.
A Small RNA‐Based Immune System Defends Germ Cells against Mobile Genetic Elements
Authors: Haase Astrid D.
Published: November 2015

Transposons are mobile genetic elements that threaten the survival of species by destabilizing the germline genomes. Limiting the spread of these selfish elements is imperative. Germ cells employ specialized small regulatory RNA pathways to restrain transposon activity. PIWI proteins and Piwi‐interacting RNAs (piRNAs) silence transposons at the transcriptional and posttranscriptional level with loss‐of‐function mutant animals universally exhibiting sterility often associated with germ cell defects. This short review aims to illustrate basic strategies of piRNA‐guided defense against transposons. Mechanisms of piRNA silencing are most readily studied in Drosophila melanogaster, which serves as a model to delineate molecular concepts and as a reference for mammalian piRNA systems. PiRNA pathways utilize two major strategies to handle the challenges of transposon control: (1) the hard‐wired molecular memory of prior transpositions enables recognition of mobile genetic elements and discriminates transposons from host genes; (2) a feed‐forward adaptation mechanism shapes piRNA populations to selectively combat the immediate threat of transposon transcripts. In flies, maternally contributed PIWI‐piRNA complexes bolster both of these lines of defense and ensure transgenerational immunity. While recent studies have provided a conceptual framework of what could be viewed as an ancient immune system, we are just beginning to appreciate its many molecular innovations.
Uric Acid‐Induced Adipocyte Dysfunction Is Attenuated by HO‐1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity
Authors: Sodhi Komal , Hilgefort Jordan , Banks George , Gilliam Chelsea , Stevens Sarah , Ansinelli Hayden A. , Getty Morghan , Abraham Nader G. , Shapiro Joseph I. , Khitan Zeid
Published: November 2015

Increased uric acid levels have been implicated in the pathogenesis of metabolic syndrome. To examine the mechanisms by which this occurs, we hypothesized that an increase in heme oxygenase 1, a potent antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO) levels. We examined the effect of uric acid on adipogenesis in human mesenchymal stem cells (MSCs) in the presence and absence of cobalt protoporphyrin (CoPP), an HO‐1 inducer, and tin mesoporphyrin (SnMP), an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBPα, PPARγ, and Mest, while decreasing small lipid droplets and Wnt10b levels. We treated MSCs with fructose, a fuel source that increases uric acid levels. Our results showed that fructose increased XO expression as compared to the control and concomitant treatment with CoPP significantly decreased XO expression and uric acid levels. These beneficial effects of CoPP were reversed by SnMP, supporting a role for HO activity in mediating these effects. These findings demonstrate that increased levels of HO‐1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in downregulating XO and NADPH oxidase levels.
Correlates of Depressive Symptoms in Older Adults with Diabetes
Authors: Jones LaRita C. , Clay Olivio J. , Ovalle Fernando , Cherrington Andrea , Crowe Michael
Published: November 2015

Investigators examined correlates of depressive symptoms within a sample of older adults with diabetes. Participants completed a structured telephone interview with measures including depressive symptoms, health conditions, cognitive function, and diabetes distress. Correlations and hierarchical linear regression models were utilized to examine bivariate and covariate-adjusted correlates of depressive symptoms. The sample included 246 community-dwelling adults with diabetes (≥65 years old). In bivariate analyses, African Americans, individuals with specific health issues (neuropathy, stroke, respiratory issues, arthritis, and cardiac issues), and those with higher levels of diabetes distress reported more depressive symptoms. Older age, higher education, more income, and better cognitive function were inversely associated with depressive symptoms. In the final covariate-adjusted regression model, stroke (B= .22,p<.001), cognitive function (B= −.14,p<.01), and higher levels of diabetes-related distress (B= .49,p<.001) each were uniquely associated with more depressive symptoms. Diabetes distress partially mediated the associations between cardiac issues and depressive symptoms and between cognitive function and depressive symptoms. Findings suggest that interventions targeted at helping older adults manage their diabetes-related distress and reducing the likelihood of experiencing additional health complications may reduce depressive symptoms within this population.
Efficient and Adaptive Node Selection for Target Tracking in Wireless Sensor Network
Authors: Feng Juan , Zhao Hongwei , Lian Baowang
Published: November 2015

In target tracking wireless sensor network, choosing the proper working nodes can not only minimize the number of active nodes, but also satisfy the tracking reliability requirement. However, most existing works focus on selecting sensor nodes which are the nearest to the target for tracking missions and they did not consider the correlation of the location of the sensor nodes so that these approaches can not meet all the goals of the network. This work proposes an efficient and adaptive node selection approach for tracking a target in a distributed wireless sensor network. The proposed approach combines the distance-based node selection strategy and particle filter prediction considering the spatial correlation of the different sensing nodes. Moreover, a joint distance weighted measurement is proposed to estimate the information utility of sensing nodes. Experimental results show that EANS outperformed the state-of-the-art approaches by reducing the energy cost and computational complexity as well as guaranteeing the tracking accuracy.
Developmental Pathways Direct Pancreatic Cancer Initiation from Its Cellular Origin
Authors: Reichert Maximilian , Blume Karin , Kleger Alexander , Hartmann Daniel , von Figura Guido
Published: November 2015

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis, since it is usually diagnosed at advanced stages. In order to employ tools for early detection, a better understanding of the early stages of PDA development from its main precursors, pancreatic intraepithelial neoplasia (PanIN), and intraductal papillary mucinous neoplasm (IPMN) is needed. Recent studies on murine PDA models have identified a different exocrine origin for PanINs and IPMNs. In both processes, developmental pathways direct the initiation of PDA precursors from their cellular ancestors. In this review, the current understanding of early PDA development is summarized.
How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?
Authors: Li Liangpeng , Chen Xiongwen , Wang Wei Eric , Zeng Chunyu
Published: November 2015

Mesenchymal stem cell (MSC) is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question.
ImmunoPET with Anti-Mesothelin Antibody in Patients with Pancreatic and Ovarian Cancer before Anti-Mesothelin Antibody–Drug Conjugate Treatment
Authors: Lamberts Laetitia E. , Menke-van der Houven van Oordt Catharina W. , ter Weele Eva J. , Bensch Frederike , Smeenk Michiel M. , Voortman Johannes , Hoekstra Otto S. , Williams Simon P. , Fine Bernard M. , Maslyar Daniel , de Jong Johan R. , Gietema Jourik A. , Schröder Carolien P. , Bongaerts Alphons H.H. , Lub-de Hooge Marjolijn N. , Verheul Henk M.W. , Sanabria Bohorquez Sandra M. , Glaudemans Andor W.J.M. , de Vries Elisabeth G.E.
Published: November 2015

Purpose: Mesothelin (MSLN) is frequently overexpressed in pancreatic and ovarian cancers, making it a potential drug target. We performed an 89Zr-PET imaging study with MMOT0530A, a MSLN antibody, in conjunction with a phase I study with the antibody–drug conjugate DMOT4039A, containing MMOT0530A bound to MMAE. The aim was to study antibody tumor uptake, whole-body distribution, and relation between uptake, response to treatment, and MSLN expression.

Experimental Design: Before DMOT4039A treatment, patients received 37 MBq 89Zr-MMOT0530A followed by PET/CT imaging 2, 4, and 7 days postinjection. Tracer uptake was expressed as standardized uptake value (SUV). MSLN expression was determined with immunohistochemistry (IHC) on archival tumor tissue.

Results: Eleven patients were included, 7 with pancreatic and 4 with ovarian cancer. IHC MSLN expression varied from absent to strong. Suitable tracer antibody dose was 10 mg MMOT0530A and optimal imaging time was 4 and 7 days postinjection. Tumor tracer uptake occurred in 37 lesions with mean SUVmax of 13.1 (±7.5) on PET 4 days postinjection, with 11.5 (±7.5) in (N = 17) pancreatic and 14.5 (±8.7) in (N = 20) ovarian cancer lesions. Within patients, a mean 2.4-fold (±1.10) difference in uptake between tumor lesions existed. Uptake in blood, liver, kidneys, spleen, and intestine reflected normal antibody distribution. Tracer tumor uptake was correlated to IHC. Best response to DMOT4039A was partial response in one patient.

Conclusions: With 89Zr-MMOT0530A-PET, pancreatic and ovarian cancer lesions as well as antibody biodistribution could be visualized. This technique can potentially guide individualized antibody-based treatment. Clin Cancer Res; 22(7); 1642–52. ©2015 AACR.
Pericytes Promote Malignant Ovarian Cancer Progression in Mice and Predict Poor Prognosis in Serous Ovarian Cancer Patients
Authors: Sinha Devbarna , Chong Lynn , George Joshy , Schlüter Holger , Mönchgesang Susann , Mills Stuart , Li Jason , Parish Christopher , Bowtell David , Kaur Pritinder
Published: November 2015

Purpose: The aim of this study was to investigate the role of pericytes in regulating malignant ovarian cancer progression.

Experimental Design: The pericyte mRNA signature was used to interrogate ovarian cancer patient datasets to determine its prognostic value for recurrence and mortality. Xenograft models of ovarian cancer were used to determine if co-injection with pericytes affected tumor growth rate and metastasis, whereas co-culture models were utilized to investigate the direct effect of pericytes on ovarian cancer cells. Pericyte markers were used to stain patient tissue samples to ascertain their use in prognosis.

Results: Interrogation of two serous ovarian cancer patient datasets [the Australian Ovarian Cancer Study, n = 215; and the NCI TCGA (The Cancer Genome Atlas), n = 408] showed that a high pericyte score is highly predictive for poor patient prognosis. Co-injection of ovarian cancer (OVCAR-5 & -8) cells with pericytes in a xenograft model resulted in accelerated ovarian tumor growth, and aggressive metastases, without altering tumor vasculature. Pericyte co-culture in vitro promoted ovarian cancer cell proliferation and invasion. High αSMA protein levels in patient tissue microarrays were correlated with more aggressive disease and earlier recurrence.

Conclusions: High pericyte score provides the best means to date of identifying patients with ovarian cancer at high risk of rapid relapse and mortality (mean progression-free survival time < 9 months). The stroma contains rare yet extremely potent locally resident mesenchymal stem cells—a subset of “cancer-associated fibroblasts” that promote aggressive tumor growth and metastatic dissemination, underlying the prognostic capacity of a high pericyte score to strongly predict earlier relapse and mortality. Clin Cancer Res; 22(7); 1813–24. ©2015 AACR.
EZH2 Inhibition Blocks Multiple Myeloma Cell Growth through Upregulation of Epithelial Tumor Suppressor Genes
Authors: Hernando Henar , Gelato Kathy A. , Lesche Ralf , Beckmann Georg , Koehr Silke , Otto Saskia , Steigemann Patrick , Stresemann Carlo
Published: November 2015

Multiple myeloma is a plasma cell malignancy characterized by marked heterogeneous genomic instability including frequent genetic alterations in epigenetic enzymes. In particular, the histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2) is overexpressed in multiple myeloma. EZH2 is the catalytic component of the polycomb repressive complex 2 (PRC2), a master transcriptional regulator of differentiation. EZH2 catalyzes methylation of lysine 27 on histone H3 and its deregulation in cancer has been reported to contribute to silencing of tumor suppressor genes, resulting in a more undifferentiated state, and thereby contributing to the multiple myeloma phenotype. In this study, we propose the use of EZH2 inhibitors as a new therapeutic approach for the treatment of multiple myeloma. We demonstrate that EZH2 inhibition causes a global reduction of H3K27me3 in multiple myeloma cells, promoting reexpression of EZH2-repressed tumor suppressor genes in a subset of cell lines. As a result of this transcriptional activation, multiple myeloma cells treated with EZH2 inhibitors become more adherent and less proliferative compared with untreated cells. The antitumor efficacy of EZH2 inhibitors is also confirmed in vivo in a multiple myeloma xenograft model in mice. Together, our data suggest that EZH2 inhibition may provide a new therapy for multiple myeloma treatment and a promising addition to current treatment options. Mol Cancer Ther; 15(2); 287–98. ©2015 AACR.
Retuning of Mouse NK Cells after Interference with MHC Class I Sensing Adjusts Self-Tolerance but Preserves Anticancer Response
Authors: Wagner Arnika Kathleen , Wickström Stina Linnea , Tallerico Rossana , Salam Sadia , Lakshmikanth Tadepally , Brauner Hanna , Höglund Petter , Carbone Ennio , Johansson Maria Helena , Kärre Klas
Published: November 2015

Natural killer (NK) cells are most efficient if their targets do not express self MHC class I, because NK cells carry inhibitory receptors that interfere with activating their cytotoxic pathway. Clinicians have taken advantage of this by adoptively transferring haploidentical NK cells into patients to mediate an effective graft-versus-leukemia response. With a similar rationale, antibody blockade of MHC class I–specific inhibitory NK cell receptors is currently being tested in clinical trials. Both approaches are challenged by the emerging concept that NK cells may constantly adapt or “tune” their responsiveness according to the amount of self MHC class I that they sense on surrounding cells. Hence, these therapeutic attempts would initially result in increased killing of tumor cells, but a parallel adaptation process might ultimately lead to impaired antitumor efficacy. We have investigated this question in two mouse models: inhibitory receptor blockade in vivo and adoptive transfer to MHC class I–disparate hosts. We show that changed self-perception via inhibitory receptors in mature NK cells reprograms the reactivity such that tolerance to healthy cells is always preserved. However, reactivity against cancer cells lacking critical MHC class I molecules (missing self-reactivity) still remains or may even be increased. This dissociation between activity against healthy cells and tumor cells may provide an answer as to why NK cells mediate graft-versus-leukemia effects without causing graft-versus-host disease and may also be utilized to improve immunotherapy. Cancer Immunol Res; 4(2); 113–23. ©2015 AACR.
Identification of Anti-CA125 Antibody Responses in Ovarian Cancer Patients by a Novel Deep Sequence–Coupled Biopanning Platform
Authors: Frietze Kathryn M. , Roden Richard B.S. , Lee Ji-Hyun , Shi Yang , Peabody David S. , Chackerian Bryce
Published: November 2015

High-grade epithelial ovarian cancer kills more women than any other gynecologic cancer and is rarely diagnosed at an early stage. We sought to identify tumor-associated antigens (TAA) as candidate diagnostic and/or immunotherapeutic targets by taking advantage of tumor autoantibody responses in individuals with ovarian cancer. Plasma-derived IgG from a pool of five patients with advanced ovarian cancer was subjected to iterative biopanning using a library of bacteriophage MS2 virus-like particles (MS2-VLPs) displaying diverse short random peptides. After two rounds of biopanning, we analyzed the selectant population of MS2-VLPs by Ion Torrent deep sequencing. One of the top 25 most abundant peptides identified (DISGTNTSRA) had sequence similarity to cancer antigen 125 (CA125/MUC16), a well-known ovarian cancer–associated antigen. Mice immunized with MS2-DISGTNTSRA generated antibodies that cross-reacted with purified soluble CA125 from ovarian cancer cells but not membrane-bound CA125, indicating that the DISGTNTSRA peptide was a CA125/MUC16 peptide mimic of soluble CA125. Preoperative ovarian cancer patient plasma (n = 100) was assessed for anti-DISGTNTSRA, anti-CA125, and CA125. Patients with normal CA125 (<35 IU/mL) at the time of diagnosis had significantly more antibodies to DISGTNTSRA and to CA125 than those patients who had high CA125 (>35 IU/mL). A statistically significant survival advantage was observed for patients who had either normal CA125 and/or higher concentrations of antibodies to CA125 at the time of diagnosis. These data show the feasibility of using deep sequence–coupled biopanning to identify TAA autoantibody responses from cancer patient plasma and suggest a possible antibody-mediated mechanism for low CA125 plasma concentrations in some ovarian cancer patients. Cancer Immunol Res; 4(2); 157–64. ©2015 AACR.
Radiologic Heterogeneity in Responses to Anti–PD-1/PD-L1 Therapy in Metastatic Renal Cell Carcinoma
Authors: de Velasco Guillermo , Krajewski Katherine M. , Albiges Laurence , Awad Mark M. , Bellmunt Joaquim , Hodi F. Stephen , Choueiri Toni K.
Published: November 2015

Radiologic assessment of tumor response remains a challenge in patients treated with immune checkpoint inhibitors. In metastatic melanoma, for example, a spectrum of imaging patterns in response to immunotherapies have been recognized and associated with clinical benefit. In metastatic renal cell carcinoma (mRCC), less than half of patients treated with immune checkpoint inhibitors achieve objective responses, but some of the responses have been durable. In this series, five different imaging patterns of response and progression are described in mRCC patients treated with anti–PD-1/PD-L1 agents: (i) early and complete response, (ii) pseudoprogression, (iii) disease stability before ultimate response, (iv) mixed response with new lesions, and (v) early progression/primary refractory disease. The implications of the different imaging patterns of patient responses on disease prognosis are discussed and highlight the need for individualized patient assessment when using these novel immune-targeted agents. Cancer Immunol Res; 4(1); 12–17. ©2015 AACR.