Array Features Research Articles

Analysis of hybridization on the molecular barcode GeneChip microarray

Microarrays have been developed for analysis of transcriptional profiles in many organisms. For experimental simplicity and systems for which microarrays do not exist, it would be desirable to use a standard microarray platform for the analysis of multiple systems. The molecular barcode (MB) Affymetrix GeneChip could serve as such a platform. The reproducibility and quantitative capacity of the MB GeneChip were examined. Using mixed PCR templates of defined template quantity, the individual concentration responses of 384 array features were measured and shown to be highly reproducible. Moreover, the binding behaviors of the mismatched array features mirror those of the matched features, at reduced intensity. Additional analysis defined the importance of particular sequence motifs in the prediction of high-affinity and low-affinity target hybridization. The data support the future application of MB GeneChips for quantitative applications. It is proposed that at least seven orders-of-magnitude in accurate concentration sensitivity could be achieved.

Production issues for high aspect ratio Lobster-eye optics using LIGA

We have previously considered some of the parameters for, and production issues involved in making, a useful Lobster-eye prototype using X-ray lithography. Due to the high aspect ratio and dense packing of the array features, we were unable, in our initial attempts to produce optimal Lobster-eye optics using X-ray lithography and a PMMA resist, to consistently overcome adhesion issues between the substrate and the resist. In recent work we have overcome this problem by using SU-8 as the resist instead. In the light of this advance we reconsider the relevant parameters and production issues when using SU-8 and lower-energy exposures.

Merging of Systolic Messy Arrays Based on Data Flows

This paper introduces a method of merging systolic messy arrays. A systolic messy array features data-triggered PEs placed in various directions in a 2-dimensional lattice plane. The two kinds of merging are described as Shared-array and Interlacing-array. A shared-array is a systolic messy array where at least two systolic messy arrays share portions of their arrays and the data on the portions is shared with all systolic messy arrays. An interlacing-array is a systolic messy array where at least two systolic messy arrays share portions of their arrays but where the data on the portions is not shared. The data on the portions flows independently so that an interlacing-array can deal with each of its own calculations without interference. Several examples of the two kinds of merging are presented and their construction methods are illustrated.

Halbach-Magnet-Array-Based Focusing Actuator for Small-Form-Factor Optical Storage Device

Small-form-factor optical data storage devices are being developed rapidly nowadays. In the case of a CF-II-type optical data storage device (43×36×5 mm3), its components such as the disk, head, focusing actuator, and spindle motor should be assembled within a 5 mm thickness. Since the thickness specification is tight, each component should be designed to have a small thickness. In this paper, a Halbach magnet array is proposed for the focusing actuator. The proposed Halbach magnet array has the advantage of a thin actuation structure without sacrificing flux densities due to its special magnet array feature that increases the magnetic flux on one side without using a yoke. By finite element method (FEM) analysis, flux density, actuation force and actuator thickness are compared with those of conventional methods. Each dimension of the array is obtained to achieve higher performances. Finally, the working range and the resolution of the focusing actuator are experimentally obtained to verify the feasibility of the proposed idea.

Prediction of Lymph Node Metastasis in Patients with Endometrioid Endometrial Cancer Using Expression Microarray

To characterize the gene expression profiles of endometrioid endometrial cancers associated with lymph node metastasis in an effort to identify genes associated with metastatic spread. Tumors from 41 patients with endometrioid endometrial cancer grossly confined to the uterine cavity were evaluated. Positive lymph nodes were noted in 12 of 41 patients. RNA was analyzed for gene expression using the Affymetrix HG133A and HG133B GeneChip set, representing 45,000 array features covering >28,000 UniGene clusters. Data analysis was done using multidimensional scaling, binary comparison, and hierarchical clustering. Gene expression for several differentially expressed genes was examined using quantitative PCR. Gene expression data was obtained from 30,964 genes that were detected in at least 5% of the cases. Supervised analysis of node-positive versus node-negative cases indicated that 450 genes were significantly differentially expressed between the two classes at P < 0.005, 81 of which were differentially expressed by at least 2-fold at P < 0.005. Overexpressed genes included two cell cycle checkpoint genes, CDC2 and MAD2L1, which have previously been described in association with lymph node metastasis in other cancer types. The ZIC2 zinc finger gene was overexpressed in endometrial cancers with positive nodes versus those with negative nodes. Gene expression profiling of the primary tumors in patients with endometrioid endometrial cancers seems promising for identifying genes associated with lymph node metastasis. Future studies should address whether the status of nodal metastasis can be determined from the expression profiles of preoperative tissue specimens.

Designable electron transport features in one-dimensional arrays of metallic nanoparticles: Monte Carlo study of the relation between shape and transport

We study the current and shot noise in a linear array of metallic nanoparticles taking explicitly into consideration their discrete electronic spectra. Phonon assisted tunneling and dissipative effects on single nanoparticles are incorporated as well. The capacitance matrix which determines the classical Coulomb interaction within the capacitance model is calculated numerically from a realistic geometry. A Monte Carlo algorithm which self-adapts to the size of the system allows us to simulate the single-electron transport properties within a semiclassical framework. We present several effects that are related to the geometry and the one-electron level spacing like e.g. a negative differential conductance (NDC) effect. Consequently these effects are designable by the choice of the size and arrangement of the nanoparticles.

Nonplanar trapezoidal tooth log‐periodic antennas: Design and electromagnetic modeling

Nonplanar trapezoidal tooth log‐periodic (LP) antennas are investigated by combining the wisdom of theoretical design procedures with the power of accurate numerical simulation environments. Once the theoretical design is completed, electromagnetic simulations employing accurate integral equation solvers are utilized to test and correct the original design. A two‐element array of trapezoidal tooth LP antennas is designed. The array features beam‐steering ability as a novelty, in addition to frequency independence and higher directivity. Beam steering is achieved by optimizing the excitation coefficients of the two LP antennas.

Fabrication and optical characterization of imaging fiber-based nanoarrays

In this paper, we present a technique for fabricating arrays containing a density at least 90 times higher than previously published. Specifically, we discuss the fabrication of two imaging fiber-based nanoarrays, one with 700 nm features, another with 300 nm features. With arrays containing up to 4.5 × 10 6 array elements/mm 2, these nanoarrays have an ultra-high packing density. A straightforward etching protocol is used to create nanowells into which beads can be deposited. These beads comprise the sensing elements of the nanoarray. Deposition of the nanobeads into the nanowells using two techniques is described. The surface characteristics of the etched arrays are examined with atomic force microscopy and scanning electron microscopy. Fluorescence microscopy was used to observe the arrays. The 300 nm array features and the 500 nm center-to-center distance approach the minimum feature sizes viewable using conventional light microscopy.

Studies of suppression of the reflected wave and beam-scanning features of the antenna arrays

This paper describes a two-directional linear scanned design by integrating a short leaky-wave antenna (LWA) with aperture-coupled patch antenna arrays. This architecture proposes a technique not only having the advantage of suppressing the back-lobe due to the reflected wave in the short LWA but also producing two separate linearly scanned beams, each of them radiating in a different region of space (in both the front side and backside of the LWA). In this design, most of the reflected wave of the short LWA is coupled to the patch antenna arrays on the backside of the substrate. The phase of this coupled signal to each antenna element is adjusted by tuning the individual phase shifter in order to control electronically the patch antenna main beam in the cross plane (x<0). Meanwhile, on the front side, the main beam of the short LWA can be simultaneously scanned in the elevation plane (x>0) by changing the operating frequency. Hence, the two linear beam-scanning radiation patterns of individual direction can be created independently, including a narrow beam in the elevation plane (xy plane at x>0) at the front side and a broadside beam in the cross plane (xz plane at x<0) on the backside. The measured results show that the reflected wave of the short LWA in the proposed design is suppressed 8 dB as compared with a traditional short LWA without the aperture-coupled antenna arrays at 10.5 GHz. As a result, this novel architecture provides more flexibility both in the upward elevation plane (H plane) and the downward cross plane (backside-E plane) for possible beam-scanning applications in microwave communications and remote identification.

Ultrahigh density microarrays of solid samples

We present a sectioning and bonding technology to make ultrahigh density microarrays of solid samples, cutting edge matrix assembly (CEMA). Maximized array density is achieved by a scaffold-free, self-supporting construction with rectangular array features that are incrementally scalable. This platform technology facilitates arrays of >10,000 tissue features on a standard glass slide, inclusion of unique sample identifiers for improved manual or automated tracking, and oriented arraying of stratified or polarized samples.

Gene Expression Profiling of Microsatellite Unstable and Microsatellite Stable Endometrial Cancers Indicates Distinct Pathways of Aberrant Signaling

Microsatellite instability (MSI) is a molecular phenotype present in approximately 25% of endometrial cancers. We examined the global gene expression profiles of early-stage endometrioid endometrial cancers with and without the MSI phenotype to test the hypothesis that MSI phenotype may determine a unique molecular signature among otherwise similar cancers. Unsupervised principal component analysis of the expression data from these cases indicated two distinct groupings of cancers based on MSI phenotype. A relatively small number of array features (392) at high statistical value (P < 0.001) were identified that drive the instability signature in these cancers; 109 of these transcripts differed by at least 2-fold. These data identify distinct gene expression profiles for MSI and microsatellite stable (MSS) cancers, which suggest that cancers with MSI develop in part by different mechanisms from their similar stable counterparts. In particular, we found evidence that two members of the secreted frizzled related protein family (SFRP1 and SFRP4) were more frequently down-regulated in MSI cancers as compared with MSS cancers. Down-regulation was accompanied by promoter hypermethylation for SFRP1. SFRP1 was hypermethylated in 8 of 12 MSI cancers whereas only 3 of 16 MSS cancers were methylated. The WNT target fibroblast growth factor 18 was found to be up-regulated in MSI cancers. These data classify histologically similar endometrioid endometrial cancers into two distinct groupings with implications affecting therapy and prevention.

Visual attention deficits in Alzheimer's disease--a fMRI study

目的 采用功能磁共振成像(functional MRI, fMRI)技术考察Alzheimer病(AD)视觉注意缺陷的原因,并对其相应的神经解剖基础进行初步探讨.方法 13例临床诊断可能为AD的患者和13例年龄、性别与之相匹配的健康老年人参加了2种不同视觉搜索的实验测试(即联合特征搜索和子集搜索任务:其中的靶刺激均具有2个特征,但前者是通过特征捆绑策略,后者是通过项目分组形成子集来完成任务).同时采用Siemens Sonata 1.5 T成像系统, 采集其脑部fMRI数据,通过功能神经成像分析软件SPM 99 (statistical parametric mapping software, SPM)进行统计分析得到脑功能活动的图像.结果尽管2个研究组在完成不同搜索任务时的脑区大部分相互重叠,包括顶叶、额叶、颞枕交界区、原始视皮层和皮层下结构等脑区,但不同脑区的激活强度和范围明显不同,AD组主要表现为双侧顶叶和左侧额叶激活减少,并以子集搜索任务时的组间差异更显著.结论 AD患者在项目分组和特征捆绑方面均存在一定程度功能失调,其视觉注意缺陷可能是由于顶叶病变使注意焦点在不同空间位置转换困难所致,同时伴有前扣带回和前额叶功能不良。

ADF95: Tool for automatic differentiation of a FORTRAN code designed for large numbers of independent variables

ADF95 is a tool to automatically calculate numerical first derivatives for any mathematical expression as a function of user defined independent variables. Accuracy of derivatives is achieved within machine precision. ADF95 may be applied to any FORTRAN 77/90/95 conforming code and requires minimal changes by the user. It provides a new derived data type that holds the value and derivatives and applies forward differencing by overloading all FORTRAN operators and intrinsic functions. An efficient indexing technique leads to a reduced memory usage and a substantially increased performance gain over other available tools with operator overloading. This gain is especially pronounced for sparse systems with large number of independent variables. A wide class of numerical simulations, e.g., those employing implicit solvers, can profit from ADF95. Program summary Title of program: ADF95 Catalogue identifier: ADVI Program summary URL: http://cpc.cs.qub.ac.uk/summaries/ADVI Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Computer for which the program is designed: all platforms with a FORTRAN 95 compiler Programming language used: FORTRAN 95 No. of lines in distributed program, including test data, etc.: 3103 No. of bytes in distributed program, including test data, etc.: 9862 Distribution format: tar.gz Nature of problem: In many areas in the computational sciences first order partial derivatives for large and complex sets of equations are needed with machine precision accuracy. For example, any implicit or semi-implicit solver requires the computation of the Jacobian matrix, which contains the first derivatives with respect to the independent variables. ADF95 is a software module to facilitate the automatic computation of the first partial derivatives of any arbitrarily complex mathematical FORTRAN expression. The program exploits the sparsity inherited by many set of equations thereby enabling faster computations compared to alternate differentiation tools Solution method: A class is constructed which applies the chain rule of differentiation to any FORTRAN expression, to compute the first derivatives by forward differencing. An efficient indexing technique leads to a reduced memory usage and a substantially increased performance gain when sparsity can be exploited. From a users point of view, only minimal changes to his/her original code are needed in order to compute the first derivatives of any expression in the code Restrictions: Processor and memory hardware may restrict both the possible number of independent variables and the computation time Unusual features: ADF95 can operate on user code that makes use of the array features introduced in FORTRAN 90. A convenient extraction subroutine for the Jacobian matrix is also provided Running time: In many realistic cases, the evaluation of the first order derivatives of a mathematical expression is only six times slower compared to the evaluation of analytically derived and hard-coded expressions. The actual factor depends on the underlying set of equations for which derivatives are to be calculated, the number of independent variables, the sparsity and on the FORTRAN 95 compiler

Hydrogel Biosensor Array Platform Indexed by Shape

A multi-analyte sensor array platform has been developed which consists of analyte specific features that are indexed by shape. The array features are batch-fabricated lithographically from poly(ethylene glycol) diacrylate hydrogel pre-polymer and can accommodate a wide variety of different sensing chemistries. Depending on the physical scale of the sensing moiety, it is either copolymerized to the hydrogel matrix (e.g., oligonucleotides, aptamers), or it is merely physically encapsulated, an important strategy for preserving the biological activity of the larger and more complex sensing elements (e.g., antibodies, proteins, cells). This three-dimensional hydrogel sensor platform has an advantage over two-dimensional platforms in that it offers an increased signal density, and because the array is constructed of poly(ethylene glycol), it has virtually no background noise due to nonspecific adsorption of labeled analytes. To highlight the capabilities of this platform to make high signal-to-noise measurements using diverse sensing chemistries, two demonstrations are described herein that illustrate the platform's efficacy in oligonucleotide sensing and cell-based sensing.

Arrays for the combinatorial exploration of cell adhesion.

A new method for the fabrication of arrays of self-assembled monolayers (SAMs) of alkane thiols (ATs) on gold to combinatorially assay surfaces for cell adhesion is reported. A fluorous SAM, which is both cytophobic and solvophobic, was used as the background between the array features. The resulting solvophobic background permits the application of an assembly after conjugation strategy for fabrication. SAMs containing mixtures of ATs and peptide-terminated ATs were generated. Multiple cell types demonstrated differential and specific binding to these surfaces. Additionally, pluripotent human embryonic stem cells proliferated on surfaces generated by this method.

Diversity Arrays Technology (DArT) for whole-genome profiling of barley.

Diversity Arrays Technology (DArT) can detect and type DNA variation at several hundred genomic loci in parallel without relying on sequence information. Here we show that it can be effectively applied to genetic mapping and diversity analyses of barley, a species with a 5,000-Mbp genome. We tested several complexity reduction methods and selected two that generated the most polymorphic genomic representations. Arrays containing individual fragments from these representations generated DArT fingerprints with a genotype call rate of 98.0% and a scoring reproducibility of at least 99.8%. The fingerprints grouped barley lines according to known genetic relationships. To validate the Mendelian behavior of DArT markers, we constructed a genetic map for a cross between cultivars Steptoe and Morex. Nearly all polymorphic array features could be incorporated into one of seven linkage groups (98.8%). The resulting map comprised approximately 385 unique DArT markers and spanned 1,137 centimorgans. A comparison with the restriction fragment length polymorphism-based framework map indicated that the quality of the DArT map was equivalent, if not superior, to that of the framework map. These results highlight the potential of DArT as a generic technique for genome profiling in the context of molecular breeding and genomics.

Genomic DNA as a cohybridization standard for mammalian microarray measurements.

A persistent design problem for ratiometric microarray studies is selecting the 'denominator' RNA cohybridization standard. The ideal standard should be readily available, inexpensive, invariant over time and from laboratory to laboratory, and should represent all genes with a uniform signal. RNA references (both commercial 'universal' and experiment--specific types), fall short of these goals. We show here that mouse genomic DNA is a reliable microarray cohybridization standard which can meet these criteria. Genomic DNA was superior in universality of coverage (>98% of genes from a 16,000 feature mouse 70mer microarray) to the Stratagene Universal Mouse Reference RNA standard. Ratios for genes in very low abundance in the Stratagene standard were more unstable with the Stratagene standard than with genomic DNA. Genes with mid-range, and therefore presumably optimal RNA denominator values, showed comparable reproducibility with both standards. Inferred ratios made between two different experimental RNAs using a genomic DNA standard were found to correlate well with companion, directly measured ratios (Spearman correlation coefficient = 0.98). The advantage in array feature coverage of genomic DNA will likely increase as newer generation microarrays include genes which are expressed exclusively in minor tissue or developmental domains that are not represented in mixed tissue RNA standards.

Combinatorial decoding: an approach for universal DNA array fabrication.

A fiber optic microsphere-based oligonucleotide array is described that employs the sequence of the oligonucleotide probe attached to each microsphere as positional identifiers. Each microsphere serves as an immobilized array feature, functionalized with a unique single-stranded oligonucleotide sequence and randomly distributed into an array of microwells. To determine the sequences attached to individual microspheres, a series of fluorescently labeled combinatorial-pooled oligonucleotide target solutions was designed. Each combinatorial decoding solution is intended to identify the nucleotide at a particular position on every microsphere in the array. The combinatorial target solutions were synthesized by linking the four possible nucleotides at each position to four different fluorescent reporter dyes. As such, when the solutions were hybridized to the array, one of four possible fluorescent responses was generated for each position on a microsphere probe sequence. Adjusting the stringency of hybridization enabled single-base mismatch discrimination, and the signal with the highest intensity corresponded to the perfect nucleotide match. By consecutively exposing the array to a series of combinatorial decoding pool solutions, it was possible to simultaneously determine the sequence of every randomly positioned oligonucleotide-functionalized microsphere in the array. Once mapped, the microsphere array can be used for any typical genomic microarray experiment.

Gene arrays are not just for measuring gene expression

Recent advances in the application of high-density oligonucleotide arrays offer new opportunities for gene discovery through genotyping several hundred thousand loci in a single assay. This is accomplished by hybridizing labeled total genomic DNA to a GeneChip rather than using mRNA, which measures gene transcript abundance. The single feature polymorphisms (SFPs) detected by this technique are the consequence of allelic variants ranging from single nucleotide polymorphisms to large deletions that differentially hybridize to the oligonucleotide array features. In yeast, this approach has proven useful in linkage mapping, the dissection of quantitative trait loci, and in assessing species population structure. Recently, the utility of this technology has been shown in the Arabidopsis genome.

Array decomposition method for the accurate analysis of finite arrays

Presented in this paper is a fast method to accurately model finite arrays of arbitrary three-dimensional elements. The proposed technique, referred to as the array decomposition method (ADM), exploits the repeating features of finite arrays and the free-space Green's function to assemble a nonsymmetric block-Toeplitz matrix system. The Toeplitz property is used to significantly reduce storage requirements and allows the fast Fourier transform (FFT) to be applied in accelerating the matrix-vector product operations of the iterative solution process. Each element of the array is modeled using the finite element-boundary integral (FE-BI) technique for rigorous analysis. Consequently, we demonstrate that the complete LU decomposition of the matrix system from a single array element can be used as a highly effective block-diagonal preconditioner on the larger array matrix system. This rigorous method is compared to the standard FE-BI technique for several tapered-slot antenna (TSA) arrays and is demonstrated to generate the same accuracy with a fraction of the storage and solution time.