bluuebunny/crossref_metadata_2025 huggingface dataset:
(Invited) Floating Gate Type SOI-FinFET Flash Memories with Different Channel Shapes and Interpoly Dielectric Materials
Authors: Liu Yongxun , Nabatame Toshihide , Matsukawa Takashi , Endo Kazuhiko , O'uchi Shinichi , Mizubayashi Wataru , Morita Yukinori , Migita Shinji , Ota Hiroyuki , Chikyow Toyohiro , Masahara Meishoku
Published: May 2016

The floating gate (FG)-type silicon-on-insulator (SOI)-FinFET flash memories with triangular-fin (TF) and rectangular-fin (RF) channels and with different interpoly dielectric (IPD) materials have been successfully fabricated using (100)- and (110)-oriented SOI wafers and orientation dependent wet etching. The electrical characteristics of the fabricated FG-type SOI-FinFET flash memories including threshold voltage (Vt) variability, program/erase (P/E) speed, memory window, endurance, and data retention at room temperature and 85 oC have been comparatively investigated. It was experimentally found that the TF channel flash memory with an Al2O3-nitride-oxide (ANO) IPD layer shows a higher P/E speed, a larger memory window, and a lower-voltage operation as compared to the RF channel flash memories with the same ANO IPD layer. Such a high performance of the TF-ANO flash memory is due to the high-k effect of the Al2O3 layer and the electric field enhancement at the sharp foot edges of the TF.
(Invited) Broadband Spectroscopic Characterization of Electrically Active Defects in Dielectrics: Monitoring the in-Service Evolution of Dialectics in Integrated System
Authors: Obeng Yaw S. , Okoro Chukwudi A , Amoah Papa K. , You Lin
Published: May 2016

Emerging nanoelectronics are been hindered by reliability challenges such as stress related failures. The chemistry and physics of the materials play crucial roles in the changes in the reliability over time, especially in low operating voltage devices which are fabricated using low temperatures processes. The low-temperature-processed materials are metastable due to the presence of reactive metastable intermediates from the precursors, and incomplete reactions within the films that result in electrically active defects in the “as deposited” films. Metrology is thus needed for the accurate quantification of the reliability impact of these defects in integrated systems. In this paper, we discuss the use of broadband microwave to detect, characterize and monitor the evolution of active defect in low-temperature processed dielectric films under simulated use conditions. The impact of thermal exposure on the behavior of electrical defects shed light on the chemical changes occurring within the dielectric films during use.
(Invited) Development of in situ Electrochemical Small-Angle Neutron Scattering (eSANS) for Simultaneous Structure and Redox Characterization of Nanoparticles
Authors: Prabhu Vivek M , Reipa Vytas , Rondinone Adam J , Formo Eric , Bonnesen Peter V
Published: May 2016

An in situ electrochemical small-angle neutron scattering (eSANS) method was developed to measure simultaneously the redox properties and size, shape and interactions of solution-dispersed nanomaterials. By combining multi-step potentials and chronocoulometry readout with SANS, the structure and redox properties of engineered nanomaterials are followed in one experiment. Specifically, ZnO nanoparticles were examined as dilute dispersions in pH buffered deuterium oxide solutions under negative electrode potentials. The ZnO disk-shaped nanoparticles undergo an irreversible size transformation upon reduction at the vitreous carbon electrode. The decrease in average nanoparticle size near a current maximum shows the reduction reaction from ZnO to Zn occurs. The eSANS method provides nanometer scale sensitivity to nanoparticle size and shape changes due to an electrochemical reaction that is crucial to understand in energy, healthcare, and other applications.
Decoupling of Ion Diffusivity and Electromobility in Porous Dielectrics
Authors: Fan Ye , Ali Rizwan , King Sean W. , Bielefeld Jeff , Orlowski Marius K
Published: May 2016

Porous back-end dielectric materials with porosity from 8% to 25%, sandwiched between Cu and W/Pt electrodes, have been investigated in terms of Cu diffusivity and mobility. In nonporous materials the diffusivity D and mobility m of charged particles such as an ion is related by the Einstein relation: μ=D q/kT. Here, we present evidence that in porous materials the diffusivity and mobility are decoupled on a global scale, even though the Einstein relation still holds locally. In porous materials, the voids lying in the path of the ion present an impenetrable barrier for ion migration. Voids can be only overcome by a detour around the obstacle by virtue of diffusion. We propose a modified relation between diffusivity and mobility in porous materials by μ=fp∙D q/kT where a porosity-tortuosity factor fp <1 is introduced. The factor fp depends on porosity and tortuosity of the porous material.
(Invited) Tunnel-Barrier Rectifiers for Optical Nantennas
Authors: Mitrovic Ivona Z. , Weerakkody Ayendra Don , Sedghi Naser , Hall Stephen , Ralph Jason F. , Wrench Jacqueline S. , Chalker Paul R. , Luo Zhenhua , Beeby Steve
Published: May 2016

We present comprehensive experimental and theoretical work on tunnel-barrier rectifiers comprising double (Nb2O5-Al2O3) and triple (Ta2O5-Nb2O5-Al2O3) insulator configurations engineered to enhance low-voltage nonlinearity. The key rectifier properties, asymmetry, nonlinearity and responsivity have been assessed from current-voltage measurements. A superior low-voltage asymmetry (12 at 0.1 V) and responsivity (5 A/W at 0.2 V) for MIIIM rectifiers have been observed. The results demonstrate enhanced rectification by atomically multi-layering tunnel barriers in cascaded and non-cascaded MIIIM arrangements, for inclusion in optical nantennas.
Electrical Properties and Nanoresistive Switching of Ni-HfO2-Si Capacitors
Authors: García Héctor , Gonzalez Mireia , Vaca Cesar , Castán Helena , Dueñas Salvador , Campabadal. Francesca , Miranda Enrique , Bailon Luis
Published: May 2016

Ni/HfO2/Si ReRAM devices were extensively characterized. In the pristine state, they show adequate performance with low leakage currents and moderate interfacial state density. Leakage current is dominated by Poole-Frenkel mechanism. Activation energies of conduction processes and soft-optical phonons in the insulator bulk are 80 and 50 meV, respectively. Both are usual values in high-k dielectrics. Devices show unipolar resistive switching behavior, with two well-defined resistance states. They can switch properly at temperatures as low as 77 K. Transitions between both resistance states are electric field and temperature dependent.
(Invited) Beyond-CMOS Device and Interconnect Technology Benchmarking Based on a Fast Cross-Layer Optimization Methodology
Authors: Pan Chenyun , Naeemi Azad
Published: May 2016

As the semiconductor industry approaches sub-20nm technology nodes, both devices and interconnects are facing severe physical challenges. Many novel device and interconnect concepts and system integration techniques are proposed in the past decade to reinforce or even replace the conventional Si CMOS technology and Cu interconnects. To efficiently benchmark and optimize these emerging technologies, a validated system-level design methodology is developed based on the compact models from all hierarchies, starting from the bottom material-level, to the device- and interconnect-level, and to the top system-level models. Multiple design parameters across all hierarchies are co-optimized simultaneously to maximize the overall chip throughput instead of just the intrinsic delay or energy dissipation of the device or interconnect itself.
(Invited) 300GHz CMOS Wireless Communication with 32 Quadrature-Amplitude-Modulation Capability
Authors: Fujishima Minoru
Published: May 2016

300GHz-band CMOS transmitter is fabricated with 40nm process. Measured results show that 17.5Gbps per channel is realized over 6 channels with 32 QAM. We have adopted a newly developed second subharmonic up-conversion mixer in a transmitter, which utilizes cubic nonlinearity in a transistor. As a result, total bit rate reaches at 105Gbps when all the 6 channels are bonded.
Development of Characterization Platform Dedicated to Bio-Inspired Objects at the Nanoscale
Authors: Carmignani Corentin , Thuaire Aurélie , Rongier Anaelle , Altamura Lucie , Brun Christophe , Reynaud Patrick , Rolland Emmanuel , David Nadine , Rannou Patrice , Forge Vincent , Ernst Thomas , Cheramy Séverine
Published: May 2016

Based on their nanoscale size and morphology, as well as on their auto-assembling properties, bio-inspired nano-objects have been identified as potential interconnection and sensor materials. Their electrical properties, namely conduction mechanism and electrical contact, have to be studied in order to enable a comparison with standard microelectronic components. In this paper, a generic characterization platform for bio-inspired nano-objects is proposed, enabling electrical investigations ranging from dry electrical measurements to wet electrochemical investigation, and for bio-inspired materials morphologies from single nanowires to films. Various electrode patterns have been designed and fabricated on 200mm silicon substrates, before being diced at chip scale and embedded in easy-to-plug systems for dry and wet measurements, including climatic chamber or glove box. Fully biocompatible microelectronic fabrication processes have been selected.
Effect of Substrate Type on CoSi2 Formation in Rapid Thermal Annealing
Authors: Kim Eun Jung , Lee Jin Yul , Kim Sang Deok , Song Han Sang , Yeom Seung Jin , Ishigaki Toshikazu , Kang Kitaek , Yoo Woo Sik
Published: May 2016

Annealing process optimization was performed to achieve low resistivity CoSi2 contacts used in different locations (word line, source, drain and gate regions) of advanced memory devices with various types of Si. The effect of Si type and annealing time on the resulting resistivity of the CoSi2 was investigated over a wide range of annealing temperatures (350 ~ 900oC) and times (60 ~ 300s) using a single wafer furnace-based (hot wall) rapid thermal annealing (RTA) system. The properties (conduction type, dopant, stacking structure and crystallinity) of the Si substrate contacting the Co film had a significant effect on the resulting CoSi2 formation temperature and contact resistance. In general, the CoSi2 formation temperature was reduced with the increase of RTA time. Significant differences in CoSi2 formation temperature was observed from different types of Si. The CoSi2 formation temperature for the source/drain (S/D) of P-type transistors was found to be the lowest. The CoSi2 formation temperature for poly Si, used in cells, was found to be the highest and was the limiting factor in RTA temperature reduction efforts.
Source/Drain Contact Resistance Reduction through Al-Doped ZnO Interlayer to Metal-Interlayer-GaAs Contact Structure
Authors: Kim Seung-Hwan , Kim Gwang-Sik , Kim Sun-Woo , Yu Hyun-Yong
Published: May 2016

We demonstrate a metal-interlayer-semiconductor structure for a non-alloyed source/drain ohmic contact by using a heavily doped ZnO. Therefore, the Fermi-level is effectively alleviated by preventing the metal induced gap state. Finally, we achieved ~105 x reduction of specific contact resistivity compared to the metal-semiconductor contact. For this reasons, the proposed contact is a promising non-alloyed source/drain ohmic contact for III-V semiconductor based devices.
Ultra-Small ZnO Nanoparticles for Charge Storage in MOS-Memory Devices
Authors: El-Atab Nazek , Nayfeh Ammar
Published: May 2016

ZnO-nanoparticles have gained considerable interest by industry and research due to their excellent properties. However, the agglomeration of nanoparticles is considered to be a limiting factor since it can affect the desirable physical and electronic properties of the nanoparticles. In this work, 1-to-5-nm-thick ZnO-nanoparticles deposited by dip-coating are studied. The results show that dip-coating leads to 1-D quantum confinement in ZnO (2-D nanostructures). Memory devices with ZnO-nanoparticles charge trapping layer show that a large memory window can be obtained at low operating-voltages due to the large available charge trap states in ZnO. Moreover, the excellent retention and endurance characteristics show that ZnO nanoparticles are promising for low-power memory applications.
Thermal-Structural Optimization of Light with LED Packaging
Authors: Zhang Liqiang , Li Yongli , Ge Daohan , Zhu X.D.
Published: May 2016

A systematic numerical and experimental method is developed to optimize a caution lamp with multichips LED chips. Here, we intend to describe the thermal performance of LED caution lamp with multiple LED chips through the structural optimization by the finite element method. One type of caution lamp was made and the highest temperatures of LED chips have been test after the optimization. This optimization method is useful for design and manufacturing of caution lamps with multiple LED chips. Compared with the simulation and the experiment data, the high temperature of LEDs were reduced by choosing fitting parameters. It indicates that the results and methods used in this paper can provide the guidance in the understanding of thermal management for LED lamps design.
Direct Detection of NT- Pro BNP As a Cardiac Biomarker Using High Electron Mobility Transistors in Physiological Salt Environment
Authors: Regmi Abiral , Sarangadharan Indu , Chen Yan Wen , Hsu Chen-Pin , Wang Yu-Lin
Published: May 2016

Cardiovascular disease (CVD) is one of the major causes to claim millions of lives all across the globe every year. While the chances of CVD increase with age, it can also occur in any age group of people, both male and female. Despite all efforts and tremendous accomplishments in the precaution and treatment of CVD, its detection at an early stage is still a big challenge for scientists in this present modern world. Here, NT-pro BNP plays a crucial role in acute congestive heart failure since it is biologically inactive, binds better with its receptors and has a longer half-life than any other, making it an ideal biomarker. The detection method is based upon the ligand-receptor interaction, also called as immunoassay, which can be successfully detected with the use of High Electron Mobility Transistors (HEMTs) with short duration pulse applied at the gate electrode. With its unique characteristic features like good electrical property, chemical stability, biocompatibility, thermal stability and low power consumption HEMT sensors also have been used in several other applications like ion-sensing, pH sensing, gas sensing, etc. Therefore, the detection method becomes simple, fast, convenient and cost effective.
Development of Solid Oxide Fuel Cells at Versa Power Systems & FuelCell Energy
Authors: Torabi Alireza , Barton Joseph , Willman Carl , Ghezel-Ayagh Hossein , Tang Eric , Pastula Michael
Published: May 2016

Versa Power Systems (VPS) is a developer of solid oxide fuel cells (SOFCs) for clean power generation and is a wholly owned subsidiary of FuelCell Energy (FCE). FCE is a global leader in the design, manufacture and distribution of Molten Carbonate Fuel Cell (MCFC) power plants. From an economic perspective, MCFCs scale-up very well and as a result FCE’s MCFC products are in the multi-megawatt size range. SOFCs are complementary because they scale-down well and hence are suited to submegawatt applications. This paper highlights the status of VPS and FCE’s SOFC technology in the areas of cell, stack and system development.
New Hypothesis for SOFC Ceramic Oxygen Electrode Mechanisms
Authors: Mogensen Mogens Bjerg , Chatzichristodoulou Christodoulos , Graves Christopher , Hansen Karin Vels , Hansen Kent Kammer , Hauch Anne , Jacobsen Torben , Norrman Kion
Published: May 2016

A new hypothesis for the electrochemical reaction mechanism in solid oxide cell ceramic oxygen electrodes is proposed based on literature including our own results. The hypothesis postulates that the observed thin layers of SrO-La2O3 on top of ceramic perovskite and other Ruddlesden-Popper structured electrode materials are sufficiently electron and oxygen ion conducting to provide reaction sites despite that the bulk phase of such an oxide layer is insulating. We claim that a few nanometer thin layer of mixed SrO-La2O3 that contains some dissolved transition metal and some impurities plus two space charge layers – one towards the gas phase and the other towards the perovskite – will be sufficiently oxide ion (vacancy) and electron conducting to support the electrode process. We also present some considerations about a possible mechanism of improved electrodes.
Thermal Properties of Perovskite-Type Oxides La0.6Sr0.4Co1-XFexO3-δ (0 ≤ x ≤ 1.0)
Authors: Shin Yu-Cheol , Hashimoto Shin-ichi , Yashiro Keiji , Amezawa Koji , Kawada Tatsuya
Published: May 2016

Perovskite-type oxides La0.6Sr0.4Co1-xFexO3-δ (LSCF) have been prepared with Co contents of 0 ≤ x ≤ 1.0 by a Pechini method and characterized by X-ray diffraction analysis. Their thermal diffusivities were measured as a function of oxygen partial pressure (PO2) in the temperature range between 873K and 1273K by a Laser Flash Method (LFA). Heat capacities were measured by TG-DSC@at heating rate 10K/min in the range of temperature between R.T and 1273K. The LSCFs thermal diffusivity was found to be a single function of oxygen deficiency, δ, independently of temperature as well as oxygen partial pressure and Co contents in intermediate temperatures range (873 to 1273K).
Time Resolved DXAS Study on Micro and Nano NiO/Ce0.9Gd0.1O1.95 Cermets for Intermediate Temperature Solid Oxide Fuel Cells
Authors: Fernandez Zuvich Afra , Larrondo Susana , Saleta Martin , Napolitano Federico , Caneiro Alberto , Troiani Horacio , Lamas Diego German , Arce Mauricio Damian , Serquis Adriana , Soldati Analia
Published: May 2016

We present a crystallographic, morphologic and redox dynamic study on (60:40) NiO/Ce0.9Gd0.1O1.95 (NiO/GDC) cermets simulating Intermediate Temperature Solid Oxide Fuel Cells (IT-SOFC) anodes in situ conditions. We tested micro- and nanometer sized materials at 700ºC in three different atmospheres (5% H2, 5% O2 and 20% CH4). We used Dispersive X-ray Absorption Spectroscopy (DXAS) analysis at the Ce L3-edge and at the Ni K-edge to follow the metal´s oxidation states. A correlation between the catalytic/redox properties and the sample´s characteristics (microstructure, Ni distribution, etc.) was found, indicating that nanometric sized particles showed faster and higher reduction extents than micrometric particles of the same composition.
Mucosal integrity and sensitivity to acid in the proximal esophagus in patients with gastroesophageal reflux disease
Authors: van Hoeij Froukje B. , Weijenborg Pim W. , van den Bergh Weerman Marius A. , van den Wijngaard René M. J. G. J. , Verheij J. , Smout André J. P. M. , Bredenoord Albert J.
Published: May 2016

Acid reflux episodes that extend to the proximal esophagus are more likely to be perceived. This suggests that the proximal esophagus is more sensitive to acid than the distal esophagus, which could be caused by impaired mucosal integrity in the proximal esophagus. Our aim was to explore sensitivity to acid and mucosal integrity in different segments of the esophagus. We used a prospective observational study, including 12 patients with gastroesophageal reflux disease (GERD). After stopping acid secretion-inhibiting medication, two procedures were performed: an acid perfusion test and an upper endoscopy with electrical tissue impedance spectroscopy and esophageal biopsies. Proximal and distal sensitivity to acid and tissue impedance were measured in vivo, and mucosal permeability and epithelial intercellular spaces at different esophageal levels were measured in vitro. Mean lag time to heartburn perception was much shorter after proximal acid perfusion (0.8 min) than after distal acid perfusion (3.9 min) ( P = 0.02). Median in vivo tissue impedance was significantly lower in the distal esophagus (4,563 Ω·m) compared with the proximal esophagus (8,170 Ω·m) ( P = 0.002). Transepithelial permeability, as measured by the median fluorescein flux was significantly higher in the distal (2,051 nmol·cm−2·h−1) than in the proximal segment (368 nmol·cm−2·h−1) ( P = 0.033). Intercellular space ratio and maximum heartburn intensity were not significantly different between the proximal and distal esophagus. In GERD patients off acid secretion-inhibiting medication, acid exposure in the proximal segment of the esophagus provokes symptoms earlier than acid exposure in the distal esophagus, whereas mucosal integrity is impaired more in the distal esophagus. These findings indicate that the enhanced sensitivity to proximal reflux episodes is not explained by increased mucosal permeability.
Alcohol breath test: gas exchange issues
Authors: Hlastala Michael P. , Anderson Joseph C.
Published: May 2016

The alcohol breath test is reviewed with a focus on gas exchange factors affecting its accuracy. The basis of the alcohol breath test is the assumption that alveolar air reaches the mouth during exhalation with no change in alcohol concentration. Recent investigations have shown that alcohol concentration is altered during its transit to the mouth. The exhaled alcohol concentration is modified by interaction with the mucosa of the pulmonary airways. Exhaled alcohol concentration is not an accurate indicator of alveolar alcohol concentration. Measuring alcohol concentration in the breath is very different process than measuring a blood level from air equilibrated with a blood sample. Airway exchange of alcohol leads to a bias against certain individuals depending on the anatomic and physiologic characteristics. Methodological modifications are proposed to improve the accuracy of the alcohol breath test to become fair to all.
Data Sets Replicas Placements Strategy from Cost-Effective View in the Cloud
Authors: Wu Xiuguo
Published: May 2016

Replication technology is commonly used to improve data availability and reduce data access latency in the cloud storage system by providing users with different replicas of the same service. Most current approaches largely focus on system performance improvement, neglecting management cost in deciding replicas number and their store places, which cause great financial burden for cloud users because the cost for replicas storage and consistency maintenance may lead to high overhead with the number of new replicas increased in a pay-as-you-go paradigm. In this paper, towards achieving the approximate minimum data sets management cost benchmark in a practical manner, we propose a replicas placements strategy from cost-effective view with the premise that system performance meets requirements. Firstly, we design data sets management cost models, including storage cost and transfer cost. Secondly, we use the access frequency and the average response time to decide which data set should be replicated. Then, the method of calculating replicas’ number and their store places with minimum management cost is proposed based on location problem graph. Both the theoretical analysis and simulations have shown that the proposed strategy offers the benefits of lower management cost with fewer replicas.
Cell Fate and Differentiation of Bone Marrow Mesenchymal Stem Cells
Authors: Kokabu Shoichiro , Lowery Jonathan W. , Jimi Eijiro
Published: May 2016

Osteoblasts and bone marrow adipocytes originate from bone marrow mesenchymal stem cells (BMMSCs) and there appears to be a reciprocal relationship between adipogenesis and osteoblastogenesis. Alterations in the balance between adipogenesis and osteoblastogenesis in BMMSCs wherein adipogenesis is increased relative to osteoblastogenesis are associated with decreased bone quality and quantity. Several proteins have been reported to regulate this reciprocal relationship but the exact nature of the signals regulating the balance between osteoblast and adipocyte formation within the bone marrow space remains to be determined. In this review, we focus on the role of Transducin‐Like Enhancer of Split 3 (TLE3), which was recently reported to regulate the balance between osteoblast and adipocyte formation from BMMSCs. We also discuss evidence implicating canonical Wnt signalling, which plays important roles in both adipogenesis and osteoblastogenesis, in regulating TLE3 expression. Currently, there is demand for new effective therapies that target the stimulation of osteoblast differentiation to enhance bone formation. We speculate that reducing TLE3 expression or activity in BMMSCs could be a useful approach towards increasing osteoblast numbers and reducing adipogenesis in the bone marrow environment.
The Impact of Social and Cultural Engagement and Dieting on Well-Being and Resilience in a Group of Residents in the Metropolitan Area of Naples
Authors: Rapacciuolo Antonio , Perrone Filardi Pasquale , Cuomo Rosario , Mauriello Vincenzo , Quarto Maria , Kisslinger Annamaria , Savarese Gianluigi , Illario Maddalena , Tramontano Donatella
Published: May 2016

Social isolation and exclusion are associated with poor health status and premature death. A number of related isolation factors, inadequate transportation system and restrictions in individuals’ life space, have been associated with malnutrition in older adults. Since eating is a social event, isolation can have a negative effect on nutrition. Cultural involvement and participation in interactive activities are essential tools to fight social isolation, and they can counteract the detrimental effects of social isolation on health. To provide data supporting the hypothesis that encouraging participation might represent an innovative preventive and health promoting strategy for healthy living and aging, we developed anad hocquestionnaire to investigate the relationship between cultural participation, well-being, and resilience in a sample of residents in the metropolitan area of Naples. The questionnaire includes a question on adherence to diet or to a special nutritional regimen; in addition, the participants are asked to mention their height and weight. We investigated the relationship between BMI, adherence to diet, and perceived well-being (PWB) and resilience in a sample of 571 subjects over 60 years of age. Here, we present evidence that engagement into social and cultural activities is associated with higher well-being and resilience, in particular in females over 60 years of age.
Preliminary Screening of Antioxidant and Antibacterial Activities and Establishment of an Efficient Callus Induction in Curculigo latifolia Dryand (Lemba)
Authors: Farzinebrahimi Reza , Mat Taha Rosna , Rashid Kamaludin A. , Ali Ahmed Bakrudeen , Danaee Mahmoud , Rozali Shahril Efzueni
Published: May 2016

Leaf, seed, and tuber explants of C. latifolia were inoculated on MS medium supplemented with various concentrations of BAP and IBA, alone or in combinations, to achieve in vitro plant regeneration. Subsequently, antioxidant and antibacterial activities were determined from in vitro and in vivo plant developed. No response was observed from seed culture on MS media with various concentrations of PGRs. The highest percentage of callus was observed on tuber explants (94%) and leaf explants (89%) when cultured on MS media supplemented with IBA in combination with BAP. A maximum of 88% shoots per tuber explant, with a mean number of shoots (8.8 ± 1.0), were obtained on MS medium supplemented with combinations of BAP and IBA (2.5 mg L−1). The best root induction (92%) and mean number (7.6 ± 0.5) from tuber explants were recorded on 2.5 mg L−1 IBA alone supplemented to MS medium. The higher antioxidant content (80%) was observed from in vivo tuber. However, tuber part from the intact plant showed higher inhibition zone in antibacterial activity compared to other in vitro and in vivo tested parts.
A Randomization Approach for Stochastic Workflow Scheduling in Clouds
Authors: Zheng Wei , Wang Chen , Zhang Dongzhan
Published: May 2016

In cloud systems consisting of heterogeneous distributed resources, scheduling plays a key role to obtain good performance when complex applications are run. However, there is unavoidable error in predicting individual task execution times and data transmission times. When this error is being not negligible, deterministic scheduling approaches (i.e., scheduling based on accurate time prediction) may suffer. In this paper, we assume the error in time predictions is modelled in stochastic manner, and a novel randomization approach making use of the properties of random variables is proposed to improve deterministic scheduling. The randomization approach is applied to a classic deterministic scheduling heuristic, but its applicability is not limited to this one heuristic. Evaluation results obtained from extensive simulation show that the randomized scheduling approach can significantly outperform its static counterpart and the extra overhead introduced is not only controllable but also acceptable.
miR-29b Mediates NF-κB Signaling in KRAS-Induced Non–Small Cell Lung Cancers
Authors: Langsch Stephanie , Baumgartner Ulrich , Haemmig Stefan , Schlup Cornelia , Schäfer Stephan C. , Berezowska Sabina , Rieger Gregor , Dorn Patrick , Tschan Mario P. , Vassella Erik
Published: May 2016

A global understanding of miRNA function in EGFR signaling pathways may provide insights into improving the management of KRAS-mutant lung cancers, which remain relatively recalcitrant to treatment. To identify miRNAs implicated in EGFR signaling, we transduced bronchial epithelial BEAS-2B cells with retroviral vectors expressing KRASG12V and monitored miRNA expression patterns by microarray analysis. Through this approach, we defined miR-29b as an important target for upregulation by mutant KRAS in non–small cell lung cancers. Cell biologic analyses showed that pharmacologic inhibition of EGFR or MEK was sufficient to reduce levels of miR-29b, while PI3K inhibition had no effect. In KRASG12V-transduced BEAS-2B cells, introduction of anti-miR-29b constructs increased the sensitivity to apoptosis, arguing that miR-29b mediated apoptotic resistance conferred by mutant KRAS. Mechanistic investigations traced this effect to the ability of miR-29b to target TNFAIP3/A20, a negative regulator of NF-κB signaling. Accordingly, overexpression of an miR-29b–refractory isoform of TNFAIP3 restored NF-κB and extrinsic apoptosis, confirming that TNFAIP3 is a functionally relevant target of miR-29b. We also noted that miR-29b could confer sensitivity to intrinsic apoptosis triggered by exposure to cisplatin, a drug used widely in lung cancer treatment. Thus, miR-29b expression may tilt cells from extrinsic to intrinsic mechanisms of apoptosis. Overall, our results reveal a complexity in cancer for miR-29b, which can act as either an oncogene or tumor suppressor gene depending on signaling context. Cancer Res; 76(14); 4160–9. ©2016 AACR.
Dietary Fat Intake During Adolescence and Breast Density Among Young Women
Authors: Jung Seungyoun , Goloubeva Olga , Klifa Catherine , LeBlanc Erin S. , Snetselaar Linda G. , Van Horn Linda , Dorgan Joanne F.
Published: May 2016

Background: Lack of association between fat intake and breast cancer risk in cohort studies might be attributed to the disregard of temporal effects during adolescence when breasts develop and are particularly sensitive to stimuli. We prospectively examined associations between adolescent fat intakes and breast density.

Method: Among 177 women who participated in the Dietary Intervention Study in Children, dietary intakes at ages 10–18 years were assessed on five occasions by 24-hour recalls and averaged. We calculated geometric mean and 95% confidence intervals for MRI-measured breast density at ages 25–29 years across quartiles of fat intake using linear mixed-effect regression.

Results: Comparing women in the extreme quartiles of adolescent fat intakes, percent dense breast volume (%DBV) was positively associated with saturated fat (mean = 16.4% vs. 21.5%; Ptrend < 0.001). Conversely, %DBV was inversely associated with monounsaturated fat (25.0% vs. 15.8%; Ptrend < 0.001) and the ratio of polyunsaturated fat to saturated fat (P/S ratio; 19.1% vs. 14.3%; Ptrend < 0.001). When examining intake by pubertal stages, %DBV was inversely associated with intake of polyunsaturated fat (20.8% vs. 16.4%; Ptrend = 0.04), long-chain omega-3 fat (17.8% vs. 15.8%; Ptrend < 0.001), and P/S ratio (22.5% vs. 16.1%; Ptrend < 0.001) before menarche, but not after. These associations observed with %DBV were consistently observed with absolute dense breast volume but not with absolute nondense breast volume.

Conclusions: In our study, adolescent intakes of higher saturated fat and lower mono- and polyunsaturated fat are associated with higher breast density measured approximately 15 years later.

Impact: The fat subtype composition in adolescent diet may be important in early breast cancer prevention. Cancer Epidemiol Biomarkers Prev; 25(6); 918–26. ©2016 AACR.
Abstract A154: KTN3379 overcomes ErbB3-mediated resistance of BRaf/MEK inhibition in BRaf-mutated melanoma
Authors: Ligon Gwenda F. , Lillquist Jay S. , LaVallee Theresa M. , Alvarado Diego
Published: May 2016

BRaf and MEK targeting drugs result in impressive tumor response rates in melanoma cancer patients, but adaptive resistance hampers the clinical benefit by limiting durability of these drugs. We used a panel of melanoma and colorectal-derived cell lines harboring activating BRaf mutations to evaluate the role of ErbB3 signaling in mediating resistance to BRaf and MEK inhibitors. Treatment of cells with vemurafenib or trametinib results in upregulation of ErbB3 cell surface levels. These cells become hypersensitive to the effects of the ErbB3 ligand NRG; addition of NRG results in a several-fold increase of phosphorylation of ErbB3 (pErbB3) and AKT (pAKT) relative to drug-untreated cells. This effect can be reverted by KTN3379- an anti-ErbB3 monoclonal antibody in clinical development- with low nanomolar IC50 values. NRG can also rescue the cytotoxic effects of BRaf or MEK inhibition making these cells resistant to treatment with BRaf or MEK inhibitors. Addition of KTN3379 re-sensitizes the tumor cells to the antiproliferative effects of vemurafenib and trametinib. Moreover, KTN3379 potentiates the antitumor effects of a BRaf/MEK inhibitor combination in an A375 mouse xenograft model. Evaluation of mRNA databases of human tumors with 403 melanoma and 2204 CRC tumors revealed a low prevalence of NRG overexpression (1.2% and 0.8%, respectively) in these tumor types where activating BRaf mutations are common. By contrast, thyroid cancer- which has a 60% prevalence of BRaf mutations- expresses high levels of NRG, supporting a potential combination of KTN3379 with a BRaf/MEK pathway inhibitor in this setting. Currently, we are evaluating the combination of KTN3379 with vemurafenib in BRaf-mutated thyroid cancer in a Phase 1 study at Memorial Sloan Kettering Cancer Center.

Citation Format: Gwenda F. Ligon, Jay S. Lillquist, Theresa M. LaVallee, Diego Alvarado. KTN3379 overcomes ErbB3-mediated resistance of BRaf/MEK inhibition in BRaf-mutated melanoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A154.
Abstract A189: FAK inhibition induces T cell-mediated tumor regression: A novel role for nuclear FAK in controlling Tregs via transcription of cytokine networks
Authors: Serrels Alan , Lund Tom , Serrels Bryan , Bryon Adam , Ring Jennifer , Pachter Jonathan A , Brunton Valerie G , Nibbs Robert J.B
Published: May 2016

It is clear that the behavior of tumors cannot be ascribed solely to cancer cell-autonomous traits that are typically monitored by tissue culture experiments. The tumor niche is composed of multiple cell types, of which only a fraction are cancer cells. It is in this context that we have discovered a completely new function of the integrin effector signaling protein Focal Adhesion Kinase (FAK) in driving anti-tumor immune evasion. Specifically, the activity of nuclear-targeted FAK in cancer cells drives recruitment and retention of intra-tumoral regulatory T-cells (Tregs) by transcriptionally regulating chemokine and cytokine ligand-receptor networks, crucially including transcription of TGFβ2 and CCL5. In turn, these changes inhibit antigen-primed cytotoxic CD8+ T-cell activity in the tumor microenvironment, permitting survival and growth of FAK-expressing tumors. We show that immune evasion requires nuclear FAK's catalytic activity and nuclear localization, and a small molecule FAK kinase inhibitor, VS-4718, which is currently in clinical development, drives depletion of Tregs and enables CD8+ T-cell-mediated tumor clearance. It is therefore likely that FAK inhibitors may trigger immune-mediated tumor regression, providing previously unrecognized therapeutic benefit. These preclinical data also suggest a novel mechanism by which a FAK inhibitor may potentiate the efficacy of checkpoint antibodies or other immunotherapeutic strategies.

Citation Format: Alan Serrels, Tom Lund, Bryan Serrels, Adam Bryon, Jennifer Ring, Jonathan A Pachter, Valerie G Brunton, Robert J.B Nibbs. FAK inhibition induces T cell-mediated tumor regression: A novel role for nuclear FAK in controlling Tregs via transcription of cytokine networks. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A189.
Abstract A200: Galectin-1-exposed dermal and tumor-associated fibroblasts produce biologically active extracellular matrix which improves growth of endothelial cells in vitro
Authors: Varinska Lenka , Mojzis Jan , Gabius Hans-Joachim , Smetana Karel , Gal Peter
Published: May 2016

The tumor microenvironment is formed by both malignant and non-malignant cells as well as by extracellular matrix (ECM) components. Stromal cells located in the tumor are primarily considered as sources of promalignant factors. Toward this end, we here address the issue of testing whether ECM affects vessel growth, considering the impact of a potent effector for conversion of fibroblasts to myofibroblasts and ECM production, i.e. the adhesion/growth-regulatory galectin-1. This endogenous lectin, known for triggering diverse cellular responses such as growth modulation, invasion or motility and production of vascular endothelial growth factor-C, is here studied for its impact on the qualities of ECM to sustain proliferation of human umbilical vein endothelial cells (HUVECs). Fibroblasts had been cultured for 10 days with the lectin, followed by removing cellular constituents after an osmotic shock. Freshly isolated HUVECs were placed on the ECM. In parallel, HUVECs were seeded on untreated and gelatin-coated surfaces as controls. A positive control for growth of HUVECs culture using medium supplemented with vascular endothelial growth factor completed the test panel. Cells were kept in contact to the substratum for two days and then processed for immunocytochemistry. HUVECs seeded on fibroblast-generated ECM presented a comparatively high degree of proliferation. Furthermore, contact to substratum produced by tumor-associated fibroblasts led to generation a meshwork especially rich in fibronectin. Galetctin-1 is apparently capable to trigger ECM production favorable for growth of HUVECs, prompting further work on characterizing structural features of the ECM and in situ correlation of lectin presence, ECM constitution and neo-angiogenesis.

Acknowledgement

This study was supported in part by the Agency for Science and Research under the contract no. APVV-0408-12 and by VEGA-1/0299/13.

Citation Format: Lenka Varinska, Jan Mojzis, Hans-Joachim Gabius, Karel Smetana, Jr., Peter Gal. Galectin-1-exposed dermal and tumor-associated fibroblasts produce biologically active extracellular matrix which improves growth of endothelial cells in vitro. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A200.
Abstract A23: CancerNet biomarker profiling panel
Authors: Chenchik Alex , Diehl Paul , Iakoubov Leonid , Frangou Costa
Published: May 2016

Background: Next-generation sequencing (NGS) is playing a transformational role in cancer discovery research; providing a powerful way to study DNA and/or RNA from clinical specimens. Unfortunately, the cost and complexity of whole genome sequencing approaches represent major barriers to use of these methodologies in routine molecular diagnostic testing. Nonetheless, a comprehensive catalog of all types of mutations in cancer opens unique opportunities for understanding the mechanism of cancer onset or progression and facilitates a more personalized approach to clinical care, including improved risk stratification and treatment selection.

Methodology: Recently developed targeted approaches reduce NGS data complexity and generate qualitative sequencing information by measurement of a subset of targets per technical replicate with minimal sample usage. To this end, we have developed a novel, multiplex PCR target enrichment-based NGS pipeline (Driver-Map) designed to comprehensively assess the genomic landscape of both solid tumors and hematologic malignancies from clinical samples. Importantly, CancerCore analyzes the genomic alterations for 569 pan-cancer driver genes. Simultaneous quantitative target gene expression analysis using multiplex quantitative RNA-Seq (Q-RNA-Seq) for ∼2,000 additional genes (CancerNet) and computational network modeling facilitates the rapid identification of cancer gene and/or pathway models to identify commonalities across tumor type(s) and supporting pharmacogenetics information.

Results: To determine the broad utility of this methodology and determine whether Driver-Map captures biologically relevant information, we apply it to clinical samples from triple-negative breast cancer (TNBC) patients and demonstrate that our approach identifies novel therapeutically tractable genes.

Conclusion: In summary, Driver-Map provides both strand-specific sequencing at single-base resolution and ‘digital’ gene expression profiling, resulting in better detection of both rare genetic variants and low abundance mRNA transcripts. Moreover, Driver-Map results in unparalleled specificity and sensitivity while increasing the cost-effectiveness for high-throughput clinical Next-Gen applications.

Citation Format: Alex Chenchik, Paul Diehl, Leonid Iakoubov, Costa Frangou. CancerNet biomarker profiling panel. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A23.
Abstract A28: NFATC3-PLA2G15 fusion transcript identified by RNA-sequencing promotes tumor progression in colorectal cancer cells
Authors: Jang JE , Kim HP , Lee SH , Lee DW , Lim YJ , Han SW , Kim TY
Published: May 2016

In order to identify novel fusion transcripts in colorectal cancer, we carried out paired-end RNA sequencing in 28 human colorectal cancer cell lines. Fusion transcript candidates were identified using ChimeraScan and FusionMap tools. We obtained 1380 candidates having 4 or more read counts and spanning reads. Among the candidates, we selected 27 candidates for validation which harbors genes related to the Wnt signaling pathway or kinases according to KEGG or DAVID. After the targeted gene filtering step, validation using RT-PCR with fusion specific primers finally resulted in 2 intra- and 1 inter-fusion transcripts. Intra-fusion transcripts were NFATC3-PLA2G15 and AKAP13-PDE8A and inter-fusion transcript was KRT8-PKM2 each identified in colo-320, SW-480 and SNU-1235, respectively. The fusion junctions were confirmed by Sanger sequencing. NFATC3-PLA2G15 fusion transcripts consisted of exon 1-9 of NFATC3 (nuclear factor of activated T-cells, cytoplasmic 3) gene and exon 2-6 of the PLA2G15 (Phospholipase A2, Group 5) gene and both located on the same chromosome 16q. NFATC3 is known as transcription factor in the Wnt signaling pathway and regulates function of the target genes like cell proliferation, invasion and epithelial-to-mesenchymal transition (EMT). Under the experiments using siRNA in the colo-320 cell carrying fusion transcript, knockdown of the NFATC3-PLA2G15 fusion transcript decreased mRNA and protein expression of mesenchymal markers, namely vimentin (VIM), Twist-related protein 1 (TWIST1) and fibronectin (FN), and increased epithelial markers, E-cadherin (CDH1) and claudin-1 (CLDN1). Fusion transcripts knockdown also led to decrease of the invasion ability regulated by above markers. Moreover, soft agar assay showed inhibition of colony formation after fusion transcript knockdown. Fusion transcript downregulation also resulted in decrease of cell proliferation and mRNA and protein expression of cyclin D but increase in p27 level. The knockdown did not have influence in the fusion negative cell line. Collectively, these results suggest that the NFATC3-PLA2G15 fusion transcript is involved in invasion and proliferation of colorectal cancer cells.

Citation Format: JE Jang, HP Kim, SH Lee, DW Lee, YJ Lim, SW Han, TY Kim. NFATC3-PLA2G15 fusion transcript identified by RNA-sequencing promotes tumor progression in colorectal cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A28.
Abstract A36: Circulating cell-free DNA as a marker for response and resistance to BRAF and EGFR inhibition in BRAF-mutated metastatic colorectal cancer
Authors: Morris Van , Janku Filip , Huang Helen , Fu Siqing , Overman Michael , Piha-Paul Sarina , Subbiah Vivek , Kee Bryan , Tsimbierdou Apostolia , Fogelman David , Shurieqi Imad , Manuel Shanequa , Scamardo Antonio , Lanman Richard , Sommer Nicolas , Hong David , Kopetz Scott
Published: May 2016

This abstract has been withheld from publication due to its inclusion in the AACR-NCI-EORTC Molecular Targets Conference 2015 Official Press Program. It will be posted online at the time of its presentation in a press conference or in a session: 12:15 PM ET Friday, November 6.

Citation Format: Van Morris, Filip Janku, Helen Huang, Siqing Fu, Michael Overman, Sarina Piha-Paul, Vivek Subbiah, Bryan Kee, Apostolia Tsimbierdou, David Fogelman, Imad Shurieqi, Shanequa Manuel, Antonio Scamardo, Richard Lanman, Nicolas Sommer, David Hong, Scott Kopetz. Circulating cell-free DNA as a marker for response and resistance to BRAF and EGFR inhibition in BRAF-mutated metastatic colorectal cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A36.