Array Features Research Articles

Design and implementation of a 6-GHz array of four differential VCOs coupled through a resistive network

This paper presents the design and the implementation of a fully monolithic coupled-oscillator array, operating at 6 GHz with close to zero coupling phase, in 0.25 μm BICMOS SiGe process. This array is made of four LC-NMOS differential VCOs coupled through a resistor. The single LC-NMOS VCO structure is designed and optimized in terms of phase noise with a graphical optimization approach while satisfying design constraints. At 2.5 V power supply voltage, and a power dissipation of only 125 mW, the coupled oscillators array features a simulated phase noise of -127.3 dBc/Hz at 1 MHz frequency offset from a 6 GHz carrier, giving a simulated phase progression that was continuously variable over the range -64° < Δphi <64 ° and -116° < Δphi < 116°. This constant phase progression can be established by slightly detuning the peripheral array elements, while maintaining mutual synchronization.

Periodic arrays of gold nano-disks coupled with evanescent spectroscopy

We study and analyze various spectral features of gold nano-disk arrays coupled with the evanescent field of an optical waveguide using finite difference time domain simulations for comparison to our previous work on this topic [Jiang et al., J. Lightwave Technol. 27(13), 2264–2270 (2009)]. We find that the quadrupolar and dipolar peaks are both heavily dependent on the coherent interactions of the periodic array and show comparable performance for refractive index sensing applications. We also find sharp extinction peaks and dips in the simulated spectra, but they are not sensitive to the index change of the surface-bound layer. A detailed analysis on these sharp features reveals that the sharp extinction peaks are grating-induced quadrupolar modes and the dips represent the suppressed plasmon resonances caused by the photonic band gap.

Global Analysis of mRNA Half-Lives and de novo Transcription in a Dinoflagellate, Karenia brevis

Dinoflagellates possess many physiological processes that appear to be under post-transcriptional control. However, the extent to which their genes are regulated post-transcriptionally remains unresolved. To gain insight into the roles of differential mRNA stability and de novo transcription in dinoflagellates, we biosynthetically labeled RNA with 4-thiouracil to isolate newly transcribed and pre-existing RNA pools in Karenia brevis. These isolated fractions were then used for analysis of global mRNA stability and de novo transcription by hybridization to a K. brevis microarray. Global K. brevis mRNA half-lives were calculated from the ratio of newly transcribed to pre-existing RNA for 7086 array features using the online software HALO (Half-life Organizer). Overall, mRNA half-lives were substantially longer than reported in other organisms studied at the global level, ranging from 42 minutes to greater than 144 h, with a median of 33 hours. Consistent with well-documented trends observed in other organisms, housekeeping processes, including energy metabolism and transport, were significantly enriched in the most highly stable messages. Shorter-lived transcripts included a higher proportion of transcriptional regulation, stress response, and other response/regulatory processes. One such family of proteins involved in post-transcriptional regulation in chloroplasts and mitochondria, the pentatricopeptide repeat (PPR) proteins, had dramatically shorter half-lives when compared to the arrayed transcriptome. As transcript abundances for PPR proteins were previously observed to rapidly increase in response to nutrient addition, we queried the newly synthesized RNA pools at 1 and 4 h following nitrate addition to N-depleted cultures. Transcriptome-wide there was little evidence of increases in the rate of de novo transcription during the first 4 h, relative to that in N-depleted cells, and no evidence for increased PPR protein transcription. These results lend support to the growing consensus of post-transcriptional control of gene expression in dinoflagellates.

Characterization of Influenza Vaccine Immunogenicity Using Influenza Antigen Microarrays

BackgroundExisting methods to measure influenza vaccine immunogenicity prohibit detailed analysis of epitope determinants recognized by immunoglobulins. The development of highly multiplex proteomics platforms capable of capturing a high level of antibody binding information will enable researchers and clinicians to generate rapid and meaningful readouts of influenza-specific antibody reactivity.MethodsWe developed influenza hemagglutinin (HA) whole-protein and peptide microarrays and validated that the arrays allow detection of specific antibody reactivity across a broad dynamic range using commercially available antibodies targeted to linear and conformational HA epitopes. We derived serum from blood draws taken from 76 young and elderly subjects immediately before and 28±7 days post-vaccination with the 2008/2009 trivalent influenza vaccine and determined the antibody reactivity of these sera to influenza array antigens.ResultsUsing linear regression and correcting for multiple hypothesis testing by the Benjamini and Hochberg method of permutations over 1000 resamplings, we identified antibody reactivity to influenza whole-protein and peptide array features that correlated significantly with age, H1N1, and B-strain post-vaccine titer as assessed through a standard microneutralization assay (p<0.05, q <0.2). Notably, we identified several peptide epitopes that were inversely correlated with regard to age and seasonal H1N1 and B-strain neutralization titer (p<0.05, q <0.2), implicating reactivity to these epitopes in age-related defects in response to H1N1 influenza. We also employed multivariate linear regression with cross-validation to build models based on age and pre-vaccine peptide reactivity that predicted vaccine-induced neutralization of seasonal H1N1 and H3N2 influenza strains with a high level of accuracy (84.7% and 74.0%, respectively).ConclusionOur methods provide powerful tools for rapid and accurate measurement of broad antibody-based immune responses to influenza, and may be useful in measuring response to other vaccines and infectious agents.

The novel c-Met inhibitor cabozantinib overcomes gemcitabine resistance and stem cell signaling in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignancies. Cancer stem cells (CSCs), which are not targeted by current therapies, may be the reason for pronounced therapy resistance. A new treatment option in phase II trials is cabozantinib that inhibits the pancreatic CSC surface marker and tyrosine kinase receptor c-Met. The purpose of this study was to evaluate the effect of cabozantinib to stem-like features and therapy resistance. Established PDA cell lines, a gemcitabine-resistant subclone, non-malignant pancreatic ductal cells and primary spheroidal cultures from patient tumors were analyzed by MTT-assay, flow cytometry, colony and spheroid formation assays, western blotting, qRT-PCR, antibody protein array, immunohistochemistry and morphological features. Cabozantinib inhibited viability and spheroid formation and induced apoptosis in malignant cells with minor effects in non-malignant cells. After long-term cabozantinib treatment, PDA cells had altered anti- and pro-apoptotic signaling, but still responded to cabozantinib, as apoptosis only slightly decreased and viability only slightly increased suggesting a low resistance-inducing potential of cabozantinib. In parallel, c-Met expression and the pluripotency transcription factor SOX2 were downregulated, which might counteract development of full therapy resistance in long-term treated subclones. In single-treatment studies, cabozantinib increased efficacy of gemcitabine. Most importantly, cabozantinib strongly induced apoptosis and reduced viability in PDA cell lines, which are completely resistant toward gemcitabine. In primary, CSC-enriched spheroidal cultures cabozantinib downregulated CSC markers SOX2, c-Met and CD133 and induced apoptosis. These findings suggest that the clinical use of cabozantinib may be more effective than current chemotherapeutics.

Influenza antigen microarrays reveal reactivity signatures associated with effective response to seasonal trivalent influenza vaccination (P4295)

Abstract Existing methods to measure influenza vaccine immunogenicity prohibit detailed analysis of epitope determinants recognized by immunoglobulins. We developed influenza hemagglutinin (HA) whole-protein and peptide microarrays and validated that the arrays allow detection of specific antibody reactivity across a broad dynamic range using commercially available antibodies targeted to linear and conformational HA epitopes. In a cohort of 76 young and elderly subjects administered with the 2007/2008 trivalent influenza vaccine, we observed reactivity to influenza whole-protein and peptide array features that correlated significantly with age and post-vaccine titer as assessed through a standard microneutralization assay. One reactive peptide correlated positively with age and negatively with seasonal H1N1 neutralization titer, implicating reactivity to this epitope in age-related defects in response to H1N1 influenza. We also generated models based on age and pre-vaccine peptide reactivity that predicted vaccine-induced neutralization of seasonal H1N1 and H3N2 influenza strains with a high level of accuracy. Our methods provide powerful tools for rapid and accurate measurement of broad antibody-based immune responses to influenza, and may be useful in measuring response to other vaccines and infectious agents.

Breaking the curse of dimensionality in quadratic discriminant analysis models with a novel variant of a Bayes classifier enhances automated taxa identification of freshwater macroinvertebrates

Macroinvertebrate samples are commonly used in biomonitoring to study changes on aquatic ecosystems. Traditionally, specimens are identified manually to taxa by human experts being time‐consuming and cost intensive. Using the image data of 35 taxa and 64 features, we propose a novel variant of the quadratic discriminant analysis for breaking the curse of dimensionality in quadratic discriminant analysis models. Our variant, called a random Bayes array (RBA), uses bagging and random feature selection similar to random forest. We explore several variations of RBA. We consider three classification (i.e taxa identification) decisions: majority vote, averaged posterior probabilities, and a novel approach; a score of weighted votes. Besides modifying the voting, we propose to weight features according to their importance instead of eliminating the least important features. We compared the performance of RBA with traditional Bayesian and several other popular classification methods and assessed how the methods behave in relation to each other and the different macroinvertebrate species. Further, we investigate how severely misclassifications affect the performance of different methods when set into a biomonitoring context. We found that the lowest and least severe classification error (i.e. most accurate taxa identification) was achieved with RBA by using averaged posterior probabilities and weighted features. Copyright © 2013 John Wiley &amp; Sons, Ltd.

Abstract 4268: Resistance to growth inhibition by transforming growth factor-beta is associated with activation of the PI3K-Akt pathway in HPV16-immortalized human keratinocytes at late stages of in vitro progression.

Abstract Transforming growth factor-beta (TGF-ß) plays a vital role in embryonic development, cell proliferation, inflammation and wound repair. The Smad proteins are the central mediators of TGF-ß signal transduction. However, recently several non-Smad pathways (ex., Erk, Jnk, p38 MAPK, PI3K-Akt) have been determined to play key roles in TGF-ß signaling. TGF-ß signaling is often disrupted in cancer, including cervical cancer. Human papillomavirus (HPV) is the main etiological agent in cervical cancer. HPV type 16 (HPV16)-immortalized human keratinocytes (HKc/HPV16) are initially very sensitive to growth inhibition by TGF-ß. However, HKc/HPV16 become increasingly resistant to TGF-ß during in vitro progression, and are completely resistant to TGF-ß-induced growth inhibition at late-stages of transformation, when they exhibit a differentiation resistant phenotype (HKc/DR). Although HKc/DR are completely resistant to the growth inhibitory effects of TGF-ß, some Smad signaling remains. A reporter construct containing tandem repeats of Smad binding elements was induced by TGF-ß in HKc/DR at about 50% of the level observed in HKc/HPV16. Furthermore, TGF-ß was capable of inducing epithelial-mesenchymal transition (EMT) in HKc/DR. To further explore TGF-ß signaling in HKc/HPV16 and HKc/DR, we used phospho specific antibody microarrays from Full Moon BioSystems. These arrays feature phospho and non-phospho pairs of specific antibodies pertinent to the TGF-ß pathway. Protein extracts from HKc/HPV16 and HKc/DR untreated or treated for 90 min with 40 pM TGF-ß were compared on the antibody microarrays. Activation of the Akt pathway by TGF-ß was observed in HKc/DR but not in HKc/HPV16. Similarly, PI3K and mTOR showed activation by TGF-ß in HKc/DR but not HKc/HPV16. We conclude that TGF-ß signals primarily through Smad-dependent pathways to inhibit cell proliferation in HKc/HPV16, but that non-canonical (non-smad) signaling through the PI3K-Akt-mTOR axis predominates in HKc/DR. Citation Format: Rupa Velidandla, Gehana Vaswani, Sangeeta Kowli, Lucia Pirisi-Creek, Kim E. Creek. Resistance to growth inhibition by transforming growth factor-beta is associated with activation of the PI3K-Akt pathway in HPV16-immortalized human keratinocytes at late stages of in vitro progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4268. doi:10.1158/1538-7445.AM2013-4268

Fabricating three-dimensional array features on metallic foil surface using overlapping laser shock embossing

Laser shock embossing is a new three-dimensional (3D) forming technique, which utilizes laser-generated shock wave to shape the workpiece with micro-mold. Micro rectangular array feature with dimensions of 500μm×450μm×14μm were successfully fabricated on metallic foil surface using overlapping laser shock embossing. The investigation reveals that 3D rectangular array features have a high spatial resolution at the micron level. However the micro rectangular features located on the overlap region is not so perfect. With further development, micro-mold based overlapping laser shock embossing holds promise for achieving large-area three-dimensional array features on metallic foil surface. And the forming experiment of the flower shape feature proves that the fabrication cost is independent of the microstructures complexity.

High-power arrays of quantum cascade laser master-oscillator power-amplifiers

We report on multi-wavelength arrays of master-oscillator power-amplifier quantum cascade lasers operating at wavelengths between 9.2 and 9.8 μm. All elements of the high-performance array feature longitudinal (spectral) as well as transverse single-mode emission at peak powers between 2.7 and 10 W at room temperature. The performance of two arrays that are based on different seed-section designs is thoroughly studied and compared. High output power and excellent beam quality render the arrays highly suitable for stand-off spectroscopy applications.

Multilevel Current-Source Inverter With FPGA Control

In this paper, a multilevel current-source inverter (MCSI) topology is analyzed. The issue of constructing a novel modular single-rating inductor MCSI is explored, taking advantage of the features of field-programmable gate arrays (FPGA) for control and gate signal generation. The proposed topology is built with identical modules where all inductors carry the same amount of current, simplifying the construction and operation of industrial applications with higher efficiency. A new state-machine approach, which is easy to implement in an FPGA, and a proper implementation of the phase-shifted carrier sinusoidal pulse width modulation (PSC-SPWM) allow both current balance in all modules and effective switching-frequency minimization. The performance of the MSCI proposed is simulated with Matlab and is verified by constructing a prototype.

Electrochemical catalytic behavior for platinum functionalized TiO2 nanotube arrays in PEM fuel cells

ABSTRACTConventional carbon electrode supports for platinum used in proton exchange membrane (PEM) fuel cell assemblies have issues related to carbon corrosion at typical cell operating and transient conditions. This corrosion gives rise to the evolution of greenhouse gases such as CO2, eventually degrading the carbon support and causing a loss of the catalyst specific area necessary to achieve the desired electrochemical performance. In this study, preliminary results are presented for Pt-functionalized TiO2 nanotube arrays as cathode catalyst supports for PEM fuel cells. The electrochemically synthesized TiO2 nanotube arrays were functionalized by different weight % of Pt via a solution-based approach using a dilute aqueous salt solution of hexachloroplatanic acid. Electron-beam based characterization techniques were used to study the structural and morphological features of the as-synthesized TiO2 nanotube arrays and functionalized Pt/TiO2 nanotube arrays. The electrochemical performance of the functionalized TiO2 nanotube arrays was studied by using cyclic voltammetry.

Efficient Combined Array Thinning and Weighting for Pattern Synthesis With a Nested Optimization Scheme

A novel procedure to thin an antenna array which synthesizes a desired pattern with the minimum number of active elements is introduced. The proposed method yields both the active elements and their corresponding excitations of a thinned array having the minimum number of active elements needed to meet several prescribed design specifications of the radiated far-field pattern. Specifications such as achieving a minimum gain, obtaining a pattern with a maximum allowable sidelobe level or synthesizing a shaped beam pattern confined into a mask are considered. Null field directions can also be added. In order to carry out the thinning, a genetic algorithm is used, while computing the excitations is carried out through linear or quadratic programming. The procedure incorporates the generalized scattering matrix analysis of an array made up of elements whose radiated field can be expressed as a spherical mode expansion, thus taking all electromagnetic effects inherently into account. Therefore, since the presence of an element can substantially alter the array features because of mutual coupling, two types of thinning are considered: removing elements or turning them off. Numerical results of arrays made up of isotropic sources, dielectric resonator antennas and microstrip patch antennas are presented.

Electrochemically fabricated nanovolcano arrays for SERS applications

Nanovolcano arrays were fabricated by electrodepositing Ni/Cu alloys into a monolayer of self-assembled nanospheres and then electrochemically etching the deposited alloy film. The fabricated nanovolcano arrays feature highly ordered hexagonally arranged concave nanobowls decorated with triangular nanopores at their interstices. After coated with Ag, the nanovolcano arrays serve as high-performance substrates for surface enhancement Raman spectroscopy (SERS) measurements. The experimental study shows that the structural features of the nanovolcano arrays, including concave nanobowls, nanopores, and their long-range orders, all contribute to the observed strong SERS enhancement in a synergetic manner, which is further confirmed by the simulation results obtained using the finite-difference time-domain method. Copyright © 2012 John Wiley & Sons, Ltd.

Nanostructured arrays of stacked graphene sheets

Molecular oxygen etching of HOPG surfaces prepatterned by Ga+ focused-ion-beam irradiation (FIB) has been used to generate large-area arrays of nanometer-sized graphite blocks. AFM and SEM imaging show that structures with lateral sizes down to ∼100 nm and heights of between 30 and 55 nm can be routinely fabricated. The trenches separating the graphite blocks form in the early oxidation stages via preferential gasification (into CO and CO2) of the gridlike amorphized carbon regions written by FIB. In the later oxidative etching stages, gasification of the graphite nanoprism faces laterally terminating the graphite blocks becomes the major reaction channel. Correspondingly, graphite blocks are (further) reduced in lateral extent while the trenches in between are widened. Raman and photoionization spectroscopies indicate that the quality of the topmost nG sheet(s) covering the blocks also decreases with increasing etching time—as the size and lateral density of defect-mediated etch pits increases. nG block arrays are useful substrates with which to probe the size-dependent properties of nanographene, as they comprise large numbers of uniform sheets (ca. 4 × 1010 cm−2 for an array of 0.5 × 0.5 μm2) thus allowing for the application of area-integrating spectroscopic methods. We demonstrate this by examining the Raman features of nG block arrays which include a graphene-rim-region fingerprint mode. Individual nG sheets can be exfoliated from nG stacks by means of electron-irradiation-induced charging. We have explored a number of printing/manipulation strategies aimed at controllable electromechanical transfer of nG sheet arrays to silicon wafers.

Template-assisted fabrication of tin and antimony based nanowire arrays

Antimony nanowires with diameters ranging from 35nm to 320nm were successfully prepared by simple, galvanostatic electrodeposition inside the pores of anodic alumina membranes from a citrate based electrolyte. The use of the potassium antimonyl tartrate electrolyte for electrodeposition results in the formation of Sb/Sb2O3 nanowires. The structural features of the nanowire arrays were investigated by FE-SEM, and the nanowire composition was confirmed by EDS and XRD measurements. A distinct peak at about 27.5° in the XRD pattern recorded for nanowires formed in the tartrate electrolyte was attributed to the presence of co-deposited Sb2O3. Three types of dense arrays of Sn–SnSb nanowires with diameters ranging from 82nm to 325nm were also synthesized by DC galvanostatic electrodeposition into the anodic aluminum oxide (AAO) membranes for the first time. Only Sn and SnSb peaks appeared in the XRD pattern and both phases seem to have a relatively high degree of crystallinity. The influence of current density applied during electrodeposition on the composition of nanowires was investigated. It was found that the Sb content in fabricated nanowires decreases with increasing current density. The diameters of all synthesized nanowires roughly correspond to the dimensions of the nanochannels of AAO templates used for electrodeposition.

Poster #59 BETTER THEORY-OF-MIND SKILLS IN CHILDREN HEARING VOICES MITIGATE THE RISK OF SECONDARY DELUSION FORMATION

Modular theory-of-mind accounts attribute poor mentalizing to disruption of a cognitive module dedicated to computing higher-order representations of primary representations (metarepresentations). Since metarepresentational capacity is needed to mentalize about other people's beliefs but is not needed to judge visual perspectives (which can be done by mentally rotating primary representations of seen objects), this view predicts that visual perspective-taking will be intact in individuals with selective mentalizing impairments. Counter to that prediction, this study found evidence of disturbed visual perspective-taking in normal adults who score higher on the personality variable of schizotypy and who are known to be relatively poor mentalizers (despite intact ability to inhibit salient inappropriate information in order to reason consequentially on the basis of hypothetical states, other than mental states). Whereas high-schizotypal adults and low-schizotypal adults did not differ in their ability to judge item questions (asking the relative location of array features), high-schizotypal adults performed more poorly than low-schizotypal adults in judging appearance questions (asking how an array would appear from another perspective) under viewer-rotation instructions (asking subjects to imagine moving themselves relative to a fixed array) and performed better than low-schizotypal adults in judging appearance questions under array-rotation instructions (asking subjects to imagine rotating an array relative to their own fixed viewer position). Based on these and other findings we conclude that poor mentalizing in normal adults is better understood as an impairment of perspective-taking (visual and/or cognitive) and introduce the concept of allocentric simulation to explain the functional basis of this perspective-taking impairment.

Large-scale highly ordered arrays of freestanding magnetic nanowires

Template-based techniques using anodic alumina oxide (AAO) templates provide cost-effective processes to fabricate metallic nanostructure arrays for diverse device applications. In this article, we demonstrate an innovative and reproducible fabrication method for realizing highly ordered arrays of freestanding Ni nanowires perpendicular to substrates. Using a multi-step process combining electrochemical perforation, chemical etching and cathodic polarization to the barrier layer of the AAO templates, large-scale (about 775 μm2) and well-aligned Ni nanowire arrays were achieved without wire agglomeration, and the length of the nanowires can reach more than 2 μm. The regularity of the nanowire array has been quantitatively analyzed and the results confirm that the regularity of the AAO template has been completely transferred to the nanowire arrays. Moreover, the structural features of the fabricated Ni nanowires are highly regular and spatially uniform concerning the homogeneous length and the monodisperse diameter; meanwhile both the length and the diameter of the nanowires are tunable. These advantageous features of the freestanding Ni nanowire arrays make them good candidate structures for device applications such as biological sensors and high-density magnetic recording media.

Dual length-scale nanotip arrays with controllable morphological features for highly sensitive SERS applications

Hexagonally ordered, dual length-scale nanotip arrays were fabricated using a combination of prism holographic lithography, reactive ion etching, and electron-beam evaporation. Double layered, face-centered cubic structures were prepared using prism holographic lithography and were used as templates for the nanotip arrays. The morphological features of the nanotip arrays were easily controlled in the subsequent etching process by varying the etching time and etchant gases. The surfaces of the nanotips were covered with, and roughened by, small protrusions. The nanotip arrays showed tunable surface-enhanced Raman scattering activities that depended on the sharpness, shape, and surface roughness. The simple tunability and high sensitivity of these nanotip arrays make them very promising as a high-fidelity sensing platform.

Mixed Ni–Cu-oxide nanowire array on conductive substrate and its application as enzyme-free glucose sensor

We report the synthesis of mixed Ni–Cu-oxide nanowire array on flexible metal substrate by a hydrothermal process and subsequent decomposition-related annealing treatment. Every single nanowire is a particles matrix with embedded NiO and CuO grains. To the best of our knowledge, this is the first report that mixed oxides exist in this aligned architecture. As an example of the functional properties of the compound materials, the mixed Ni–Cu-oxide nanowire array is investigated as the additive-free electrode for enzyme-free glucose sensor. Compared with previously reported Ni or Cu-contained biosensors, this Ni–Cu–oxide array electrode possesses higher performance. The detection limit can be as low as 0.1 μM, linear range as wide as 0.1–1200 μM and sensitivity as high as ∼1600 μA mM−1 cm−2. Besides the above, other excellent properties such as anti-interferences and long-term stability, are demonstrated as well. All these improvements can be attributed to the synergetic effect between the mixed oxide grains and the unique 1D array feature.