Showing papers by "Agilent Technologies published in 2008"

Mapping and sequencing of structural variation from eight human genomes

Abstract: Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale--particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects.

The balance of reproducibility, sensitivity, and specificity of lists of differentially expressed genes in microarray studies

Abstract: Background Reproducibility is a fundamental requirement in scientific experiments. Some recent publications have claimed that microarrays are unreliable because lists of differentially expressed genes (DEGs) are not reproducible in similar experiments. Meanwhile, new statistical methods for identifying DEGs continue to appear in the scientific literature. The resultant variety of existing and emerging methods exacerbates confusion and continuing debate in the microarray community on the appropriate choice of methods for identifying reliable DEG lists.

The fine-scale and complex architecture of human copy-number variation.

Abstract: Despite considerable excitement over the potential functional significance of copy-number variants (CNVs), we still lack knowledge of the fine-scale architecture of the large majority of CNV regions in the human genome. In this study, we used a high-resolution array-based comparative genomic hybridization (aCGH) platform that targeted known CNV regions of the human genome at approximately 1 kb resolution to interrogate the genomic DNAs of 30 individuals from four HapMap populations. Our results revealed that 1020 of 1153 CNV loci (88%) were actually smaller in size than what is recorded in the Database of Genomic Variants based on previously published studies. A reduction in size of more than 50% was observed for 876 CNV regions (76%). We conclude that the total genomic content of currently known common human CNVs is likely smaller than previously thought. In addition, approximately 8% of the CNV regions observed in multiple individuals exhibited genomic architectural complexity in the form of smaller CNVs within larger ones and CNVs with interindividual variation in breakpoints. Future association studies that aim to capture the potential influences of CNVs on disease phenotypes will need to consider how to best ascertain this previously uncharacterized complexity.

Widely tunable mode-hop free external cavity quantum cascade lasers for high resolution spectroscopy and chemical sensing

Abstract: Recent progress in the development of room temperature, continuous wave, widely tunable, mode-hop-free mid-infrared external cavity quantum cascade laser (EC-QCL) spectroscopic sources is reported. A single mode tuning range of 155 cm-1 (∼ 8% of the center wavelength) with a maximum power of 11.1 mW and 182 cm-1 (∼ 15% of the center wavelength) with a maximum power of 50 mW was obtained for 5.3 and 8.4 μm EC-QCLs respectively. This technology is particularly suitable for high resolution spectroscopic applications, multi species trace-gas detection and spectroscopic measurements of broadband absorbers. Several examples of spectroscopic measurements performed using EC-QCL based spectrometers are demonstrated.

Multimode regimes in quantum cascade lasers: From coherent instabilities to spatial hole burning

Abstract: A theoretical and experimental study of multimode operation regimes in quantum cascade lasers (QCLs) is presented. It is shown that the fast gain recovery of QCLs promotes two multimode regimes: One is spatial hole burning (SHB) and the other one is related to the Risken-Nummedal-Graham-Haken instability predicted in the 1960s. A model that can account for coherent phenomena, a saturable absorber, and SHB is developed and studied in detail both analytically and numerically. A wide variety of experimental data on multimode regimes is presented. Lasers with a narrow active region and/or with metal coating on the sides tend to develop a splitting in the spectrum, approximately equal to twice the Rabi frequency. It is proposed that this behavior stems from the presence of a saturable absorber, which can result from a Kerr lensing effect in the cavity. Lasers with a wide active region, which have a weaker saturable absorber, do not exhibit a Rabi splitting and their multimode regime is governed by SHB. This experimental phenomenology is well-explained by our theoretical model. The temperature dependence of the multimode regime is also presented.

Monitoring apparatus and method therefor

Abstract: A monitoring apparatus for detection of a malicious attack in a communications network comprises a pattern matching engine ( 406 ), a data store ( 408 ) and an alert generator ( 410, 412 ). The pattern matching engine ( 406 ) is arranged to receive a bit stream and identify a characteristic of a malicious attack from at least one datagram represented by at least part of the bit stream. The data store ( 408 ) is operably coupled to the pattern matching engine and the data store ( 408 ) is arranged to retain identification data to enable the pattern matching engine to identify the characteristic of the malicious attack. The alert generator ( 410, 412 ) is arranged to generate an alert in response to an identification of the characteristic of the malicious attack. The data store ( 408 ) is remotely updatable.

Physiological and molecular adaptations to drought in Andean potato genotypes

Abstract: The drought stress tolerance of two Solanum tuberosum subsp. andigena landraces, one hybrid (adgxtbr) and Atlantic (S. tuberosum subsp. tuberosum) has been evaluated. Photosynthesis in the Andigena landraces during prolonged drought was maintained significantly longer than in the Tuberosum (Atlantic) line. Among the Andigena landraces, 'Sullu' (SUL) was more drought resistant than 'Negra Ojosa' (NOJ). Microarray analysis and metabolite data from leaf samples taken at the point of maximum stress suggested higher mitochondrial metabolic activity in SUL than in NOJ. A greater induction of chloroplast-localized antioxidant and chaperone genes in SUL compared with NOJ was evident. ABA-responsive TFs were more induced in NOJ compared with SUL, including WRKY1, mediating a response in SA signalling that may give rise to increased ROS. NOJ may be experiencing higher ROS levels than SUL. Metabolite profiles of NOJ were characterized by compounds indicative of stress, for example, proline, trehalose, and GABA, which accumulated to a higher degree than in SUL. The differences between the Andigena lines were not explained by protective roles of compatible solutes; hexoses and complex sugars were similar in both landraces. Instead, lower levels of ROS accumulation, greater mitochondrial activity and active chloroplast defences contributed to a lower stress load in SUL than in NOJ during drought.

Transcriptome analysis reveals new insight into appressorium formation and function in the rice blast fungus Magnaporthe oryzae.

Abstract: Rice blast disease is caused by the filamentous Ascomycetous fungus Magnaporthe oryzae and results in significant annual rice yield losses worldwide. Infection by this and many other fungal plant pathogens requires the development of a specialized infection cell called an appressorium. The molecular processes regulating appressorium formation are incompletely understood. We analyzed genome-wide gene expression changes during spore germination and appressorium formation on a hydrophobic surface compared to induction by cAMP. During spore germination, 2,154 (approximately 21%) genes showed differential expression, with the majority being up-regulated. During appressorium formation, 357 genes were differentially expressed in response to both stimuli. These genes, which we refer to as appressorium consensus genes, were functionally grouped into Gene Ontology categories. Overall, we found a significant decrease in expression of genes involved in protein synthesis. Conversely, expression of genes associated with protein and amino acid degradation, lipid metabolism, secondary metabolism and cellular transportation exhibited a dramatic increase. We functionally characterized several differentially regulated genes, including a subtilisin protease (SPM1) and a NAD specific glutamate dehydrogenase (Mgd1), by targeted gene disruption. These studies revealed hitherto unknown findings that protein degradation and amino acid metabolism are essential for appressorium formation and subsequent infection. We present the first comprehensive genome-wide transcript profile study and functional analysis of infection structure formation by a fungal plant pathogen. Our data provide novel insight into the underlying molecular mechanisms that will directly benefit efforts to identify fungal pathogenicity factors and aid the development of new disease management strategies.

Acid treatment of melanoma cells selects for invasive phenotypes.

Abstract: Solid tumors become acidic due to hypoxia and upregulated glycolysis. We have hypothesized that this acidosis leads to more aggressive invasive behavior during carcinogenesis (Nature Reviews Cancer 4:891–899, 2004). Previous work on this subject has shown mixed results. While some have observed an induction of metastasis and invasion with acid treatments, others have not. To investigate this, human melanoma cells were acclimated to low pH growth conditions. Significant cell mortality occurred during acclimation, suggesting that acidosis selected for resistant phenotypes. Cells maintained under acidic conditions exhibited a greater range of motility, a reduced capacity to form flank tumors in SCID mice and did not invade more rapidly in vitro, compared to non-selected control cells. However, re-acclimation of these selected cells to physiological pH gave rise to stable populations with significantly higher in vitro invasion. These re-acclimated cells maintained higher invasion and higher motility for multiple generations. Transcriptomic analyses of these three phenotypes revealed significant differences, including upregulation of relevant pathways important for tissue remodeling, cell cycle control and proliferation. These results reinforce the hypothesis that acidosis promotes selection of stable, more invasive phenotypes, rather than inductive changes, which would be reversible.

Measuring microRNAs: Comparisons of microarray and quantitative PCR measurements, and of different total RNA prep methods

Abstract: Background: Determining the expression levels of microRNAs (miRNAs) is of great interest to researchers in many areas of biology, given the significant roles these molecules play in cellular regulation. Two common methods for measuring miRNAs in a total RNA sample are microarrays and quantitative RT-PCR (qPCR). To understand the results of studies that use these two different techniques to measure miRNAs, it is important to understand how well the results of these two analysis methods correlate. Since both methods use total RNA as a starting material, it is also critical to understand how measurement of miRNAs might be affected by the particular method of total RNA preparation used. Results: We measured the expression of 470 human miRNAs in nine human tissues using Agilent microarrays, and compared these results to qPCR profiles of 61 miRNAs in the same tissues. Most expressed miRNAs (53/60) correlated well (R > 0.9) between the two methods. Using spiked-in synthetic miRNAs, we further examined the two miRNAs with the lowest correlations, and found the differences cannot be attributed to differential sensitivity of the two methods. We also tested three widely-used total RNA sample prep methods using miRNA microarrays. We found that while almost all miRNA levels correspond between the three methods, there were a few miRNAs whose levels consistently differed between the different prep techniques when measured by microarray analysis. These differences were corroborated by qPCR measurements. Conclusion: The correlations between Agilent miRNA microarray results and qPCR results are generally excellent, as are the correlations between different total RNA prep methods. However, there are a few miRNAs whose levels do not correlate between the microarray and qPCR measurements, or between different sample prep methods. Researchers should therefore take care when comparing results obtained using different analysis or sample preparation methods.

Human Proteinpedia enables sharing of human protein data.

Abstract: Proteomic technologies, such as yeast two-hybrid, mass spectrometry (MS), protein/peptide arrays and fluorescence microscopy, yield multi-dimensional data sets, which are often quite large and either not published or published as supplementary information that is not easily searchable. Without a system in place for standardizing and sharing data, it is not fruitful for the biomedical community to contribute these types of data to centralized repositories.

Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets

Abstract: The most widely used method for detecting genome-wide protein–DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Here, we conducted the first objective analysis of tiling array platforms, amplification procedures, and signal detection algorithms in a simulated ChIP-chip experiment. Mixtures of human genomic DNA and “spike-ins” comprised of nearly 100 human sequences at various concentrations were hybridized to four tiling array platforms by eight independent groups. Blind to the number of spike-ins, their locations, and the range of concentrations, each group made predictions of the spike-in locations. We found that microarray platform choice is not the primary determinant of overall performance. In fact, variation in performance between labs, protocols, and algorithms within the same array platform was greater than the variation in performance between array platforms. However, each array platform had unique performance characteristics that varied with tiling resolution and the number of replicates, which have implications for cost versus detection power. Long oligonucleotide arrays were slightly more sensitive at detecting very low enrichment. On all platforms, simple sequence repeats and genome redundancy tended to result in false positives. LM-PCR and WGA, the most popular sample amplification techniques, reproduced relative enrichment levels with high fidelity. Performance among signal detection algorithms was heavily dependent on array platform. The spike-in DNA samples and the data presented here provide a stable benchmark against which future ChIP platforms, protocol improvements, and analysis methods can be evaluated.

Nanografting for Surface Physical Chemistry

Abstract: This article reveals the enabling aspects of nanografting (an atomic force microscopy–based lithography technique) in surface physical chemistry. First, we characterize self-assembled monolayers and multilayers using nanografting to place unknown molecules into a matrix with known structure or vice versa. The availability of an internal standard in situ allows the unknown structures to be imaged and quantified. The same approaches are applied to reveal the orientation and packing of biomolecules (ligands, DNA, and proteins) upon immobilization on surfaces. Second, nanografting enables systematic investigations of size-dependent mechanics at the nanometer scale by producing a series of designed nanostructures and measuring their Young's modulus in situ. Third, one can investigate systematically the influence of ligand local structure on biorecognition and protein immobilization by precisely engineering ligand nanostructures. Finally, we also demonstrate the regulation of the surface reaction mechanism, kin...

Design of Wide Tuning-Range CMOS VCOs Using Switched Coupled-Inductors

Abstract: Two designs of voltage-controlled oscillators (VCOs) with mutually coupled and switched inductors are presented in this paper to demonstrate that the tuning range of an LC VCO can be improved with only a small increase in phase noise and die area in a standard digital CMOS process. Particular attention is given to the layout of the inductors to maintain Q across the tuning range. In addition, different capacitive coarse-tuning methods are compared based on simulated and measured data obtained from test structures. Implemented in a 90 nm digital CMOS process, a VCO with two extra coupled inductors achieves a 61.9% tuning range with an 11.75 GHz center frequency while dissipating 7.7 mW from a 1.2 V supply. This VCO has a measured phase noise of -106 dBc/Hz at 1 MHz offset from the center frequency resulting in a higher figure-of-merit than other recently published VCOs with similar operating frequencies. In addition, the area overhead is only 30% compared to a conventional LC VCO with a single inductor.

Molecular formula and METLIN Personal Metabolite Database matching applied to the identification of compounds generated by LC/TOF-MS.

Abstract: In an effort to simplify and streamline compound identification from metabolomics data generated by liquid chromatography time-of-flight mass spectrometry, we have created software for constructing Personalized Metabolite Databases with content from over 15,000 compounds pulled from the public METLIN database (http://metlin.scripps.edu/). Moreover, we have added extra functionalities to the database that (a) permit the addition of user-defined retention times as an orthogonal searchable parameter to complement accurate mass data; and (b) allow interfacing to separate software, a Molecular Formula Generator (MFG), that facilitates reliable interpretation of any database matches from the accurate mass spectral data. To test the utility of this identification strategy, we added retention times to a subset of masses in this database, representing a mixture of 78 synthetic urine standards. The synthetic mixture was analyzed and screened against this METLIN urine database, resulting in 46 accurate mass and retention time matches. Human urine samples were subsequently analyzed under the same analytical conditions and screened against this database. A total of 1387 ions were detected in human urine; 16 of these ions matched both accurate mass and retention time parameters for the 78 urine standards in the database. Another 374 had only an accurate mass match to the database, with 163 of those masses also having the highest MFG score. Furthermore, MFG calculated a formula for a further 849 ions that had no match to the database. Taken together, these results suggest that the METLIN Personal Metabolite database and MFG software offer a robust strategy for confirming the formula of database matches. In the event of no database match, it also suggests possible formulas that may be helpful in interpreting the experimental results.

Real-time imaging using a 2.8 THz quantum cascade laser and uncooled infrared microbolometer camera

Abstract: Real-time imaging in the terahertz (THz) spectral range was achieved using a milliwatt-scale, 2.8 THz quantum cascade laser and an uncooled, 160 x 120 pixel microbolometer camera modified with Picarin optics. Noise equivalent temperature difference of the camera in the 1-5 THz frequency range was estimated to be at least 3 K, confirming the need for external THz illumination when imaging in this frequency regime. Despite the appearance of fringe patterns produced by multiple diffraction effects, single-frame and extended video imaging of obscured objects show high-contrast differentiation between metallic and plastic materials, supporting the viability of this imaging approach for use in future security screening applications.

Yamanaka factors critically regulate the developmental signaling network in mouse embryonic stem cells

Abstract: Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem (ES) cells, and their over-expression can induce pluripotency in both mouse and human somatic cells, indicating that these factors regulate the developmental signaling network necessary for ES cell pluripotency. However, systemic analysis of the signaling pathways regulated by Yamanaka factors has not yet been fully described. In this study, we identified the target promoters of endogenous Yamanaka factors on a whole genome scale using ChIP (chromatin immunoprecipitation)-on-chip in E14.1 mouse ES cells, and we found that these four factors co-occupied 58 promoters. Interestingly, when Oct4 and Sox2 were analyzed as core factors, Klf4 functioned to enhance the core factors for development regulation, whereas c-Myc seemed to play a distinct role in regulating metabolism. The pathway analysis revealed that Yamanaka factors collectively regulate a developmental signaling network composed of 16 developmental signaling pathways, nine of which represent earlier unknown pathways in ES cells, including apoptosis and cell-cycle pathways. We further analyzed data from a recent study examining Yamanaka factors in mouse ES cells. Interestingly, this analysis also revealed 16 developmental signaling pathways, of which 14 pathways overlap with the ones revealed by this study, despite that the target genes and the signaling pathways regulated by each individual Yamanaka factor differ significantly between these two datasets. We suggest that Yamanaka factors critically regulate a developmental signaling network composed of approximately a dozen crucial developmental signaling pathways to maintain the pluripotency of ES cells and probably also to induce pluripotent stem cells.

Probe device having a clip-on wireless system for extending probe tip functionality

Abstract: A probe device is provided that has a clip-on wireless device attached thereto for communicating over a wireless communication link with test equipment having a wireless transceiver attached thereto. The clip-on wireless device may have one or more components that provide additional functionality to the probe device over that which is currently available on most probe devices. Such components may include, for example, run/stop buttons, activity indicators, “headlight” LEDs, etc

Transcriptional Changes in the Hookworm, Ancylostoma caninum, during the Transition from a Free-Living to a Parasitic Larva

Abstract: Background Third-stage larvae (L3) of the canine hookworm, Ancylostoma caninum, undergo arrested development preceding transmission to a host. Many of the mRNAs up-regulated at this stage are likely to encode proteins that facilitate the transition from a free-living to a parasitic larva. The initial phase of mammalian host invasion by A. caninum L3 (herein termed “activation”) can be mimicked in vitro by culturing L3 in serum-containing medium. Methodology/Principal Findings The mRNAs differentially transcribed between activated and non-activated L3 were identified by suppression subtractive hybridisation (SSH). The analysis of these mRNAs on a custom oligonucleotide microarray printed with the SSH expressed sequence tags (ESTs) and publicly available A. caninum ESTs (non-subtracted) yielded 602 differentially expressed mRNAs, of which the most highly represented sequences encoded members of the pathogenesis-related protein (PRP) superfamily and proteases. Comparison of these A. caninum mRNAs with those of Caenorhabditis elegans larvae exiting from developmental (dauer) arrest demonstrated unexpectedly large differences in gene ontology profiles. C. elegans dauer exiting L3 up-regulated expression of mostly intracellular molecules involved in growth and development. Such mRNAs are virtually absent from activated hookworm larvae, and instead are over-represented by mRNAs encoding extracellular proteins with putative roles in host-parasite interactions. Conclusions/Significance Although this should not invalidate C. elegans dauer exit as a model for hookworm activation, it highlights the limitations of this free-living nematode as a model organism for the transition of nematode larvae from a free-living to a parasitic state.

Development of a real-time RT-PCR assay for detecting EGFRvIII in glioblastoma samples.

Abstract: Purpose: Epidermal growth factor receptor variant III (EGFRvIII) is an oncogenic, constitutively active mutant form of the EGFR that is commonly expressed in glioblastoma and is also detected in a number of epithelial cancers. EGFRvIII presents a unique antigenic target for anti-EGFRvIII vaccines and it has been shown to modulate response to EGFR kinase inhibitor therapy. Thus, detection in clinical samples may be warranted. Existing patents preclude the use of anti-EGFRvIII antibodies for clinical detection. Further, frozen tissue is not routinely available, particularly for patients treated in the community. Thus, detection of EGFRvIII in formalin-fixed paraffin-embedded (FFPE) clinical samples is a major challenge. Experimental Design: We developed a real-time reverse transcription-PCR (RT-PCR) assay for detecting EGFRvIII in FFPE samples and analyzed 59 FFPE glioblastoma clinical samples with paired frozen tissue from the same surgical resection. We assessed EGFRvIII protein expression by immunohistochemistry using two distinct specific anti-EGFRvIII antibodies and examined EGFR gene amplification by fluorescence in situ hybridization. Results: The FFPE RT-PCR assay detected EGFRvIII in 16 of 59 (27%) samples, exclusively in cases with EGFR amplification, consistent with the expected frequency of this alteration. The FFPE RT-PCR assay was more sensitive and specific for detecting EGFRvIII than either of the two antibodies alone, or in combination, with a sensitivity of 93% (95% confidence interval, 0.78-1.00) and a specificity of 98% (95% confidence interval, 0.93-1.00). Conclusion: This assay will facilitate accurate assessment of EGFRvIII in clinical samples and may aid in the development of strategies for stratifying patients for EGFRvIII-directed therapies.

Cerebral: Visualizing Multiple Experimental Conditions on a Graph with Biological Context

Abstract: Systems biologists use interaction graphs to model the behavior of biological systems at the molecular level. In an iterative process, such biologists observe the reactions of living cells under various experimental conditions, view the results in the context of the interaction graph, and then propose changes to the graph model. These graphs serve as a form of dynamic knowledge representation of the biological system being studied and evolve as new insight is gained from the experimental data. While numerous graph layout and drawing packages are available, these tools did not fully meet the needs of our immunologist collaborators. In this paper, we describe the data information display needs of these immunologists and translate them into design decisions. These decisions led us to create Cerebral, a system that uses a biologically guided graph layout and incorporates experimental data directly into the graph display. Small multiple views of different experimental conditions and a data-driven parallel coordinates view enable correlations between experimental conditions to be analyzed at the same time that the data is viewed in the graph context. This combination of coordinated views allows the biologist to view the data from many different perspectives simultaneously. To illustrate the typical analysis tasks performed, we analyze two datasets using Cerebral. Based on feedback from our collaborators we conclude that Cerebral is a valuable tool for analyzing experimental data in the context of an interaction graph model.

Daily Variations in Oligosaccharides of Human Milk Determined by Microfluidic Chips and Mass Spectrometry

Abstract: Human milk is a complex biological fluid that provides not only primary nourishment for infants but also protection against pathogens and influences their metabolic, immunologic, and even cognitive development. The presence of oligosaccharides in remarkable abundance in human milk has been associated to provide diverse biological functions including directing the development of an infant’s intestinal microflora and immune system. Recent advances in analytical tools offer invaluable insights in understanding the specific functions and health benefits these biomolecules impart to infants. Oligosaccharides in human milk samples obtained from five different individual donors over the course of a 3 month lactation period were isolated and analyzed using HPLC-Chip/TOF-MS technology. The levels and compositions of oligosaccharides in human milk were investigated from five individual donors. Comparison of HPLC-Chip/TOF-MS oligosaccharides profiles revealed heterogeneity among multiple individuals with no signific...

Chemical Characterization of the Lipid Fraction of Mexican Chia Seed (Salvia hispanica L.)

Abstract: The lipid fraction of Jalisco and Sinaloa chia seeds was analyzed for oil content, fatty acids, squalene and phytosterols. The mean oil content of seeds from these two regions was significantly (p ≤ 0.05) different, but with a similar composition of α-linolenic, linoleic, oleic, palmitic and stearic acids. Total phytosterols in the oil ranged from 7 to 17 g/kg. β-sitosterol accounted for up to 74% of the total unsaponified fraction. The seeds contained less than 0.5 g/kg of squalene. The oil is an attractive source of ω-3 linolenic acid and phytosterols but a poor source of squalene.

Load-pull + NVNA = enhanced X-parameters for PA designs with high mismatch and technology-independent large-signal device models

Abstract: X-parameters are the mathematically correct supersets of S-parameters valid for nonlinear (and linear) components under large-signal (and small-signal) conditions This work presents an automated application combining a nonlinear vector network analyzer (NVNA) instrument with automated load-pull measurements that extends the measurement and extraction of X-parameters over the entire Smith Chart The augmented X-parameter data include magnitude and phase as nonlinear functions of power, bias, and load, at each harmonic generated by the device and measured by the NVNA The X-parameters can be immediately used in a nonlinear simulator for complex microwave circuit analysis and design This capability extends the applicability of measurement-based X-parameters to highly mismatched environments, such as high-power and multi-stage amplifiers, and power transistors designed to work far from 50 ohms It provides a powerful and general technology-independent alternative, with improved accuracy and speed, to traditional large-signal device models which are typically slow to develop and typically extrapolate large-signal operation from small-signal and DC measurements

The effect of nonminimum-phase zero locations on the performance of feedforward model-inverse control techniques in discrete-time systems

Abstract: Noncollocated sensors and actuators, and/or fast sample rates with plants having high relative degree, can lead to nonminimum-phase (NMP) discrete-time zero dynamics that complicate the control system design. In this paper, we examine three stable approximate model-inverse feedforward control techniques, the nonmimimum-phase zeros ignore (NPZ-Ignore), the zero-phase-error tracking controller (ZPETC) and the zero-magnitude-error tracking controller (ZMETC), which have frequently been used for NMP systems. We analyze how the discrete-time NMP zero locations in the z-plane affect the success of the NPZ-Ignore, ZPETC, and ZMETC model-inverse techniques. We also provide simulation examples using plants based on the system identification of an atomic force microscope and a hard disk drive, showing the tradeoffs in performance relative to NMP zero locations in these different application systems.