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Description

One of the gravest dangers facing cancer patients is an extended symptom-free lull between tumor initiation and the first diagnosis. Detection of tumors is critical for effective intervention. Using the body’s immune system to detect and amplify tumor-specific signals may enable detection of cancer using an inexpensive immunoassay. Immunosignatures are

One of the gravest dangers facing cancer patients is an extended symptom-free lull between tumor initiation and the first diagnosis. Detection of tumors is critical for effective intervention. Using the body’s immune system to detect and amplify tumor-specific signals may enable detection of cancer using an inexpensive immunoassay. Immunosignatures are one such assay: they provide a map of antibody interactions with random-sequence peptides. They enable detection of disease-specific patterns using classic train/test methods. However, to date, very little effort has gone into extracting information from the sequence of peptides that interact with disease-specific antibodies. Because it is difficult to represent all possible antigen peptides in a microarray format, we chose to synthesize only 330,000 peptides on a single immunosignature microarray. The 330,000 random-sequence peptides on the microarray represent 83% of all tetramers and 27% of all pentamers, creating an unbiased but substantial gap in the coverage of total sequence space. We therefore chose to examine many relatively short motifs from these random-sequence peptides. Time-variant analysis of recurrent subsequences provided a means to dissect amino acid sequences from the peptides while simultaneously retaining the antibody–peptide binding intensities. We first used a simple experiment in which monoclonal antibodies with known linear epitopes were exposed to these random-sequence peptides, and their binding intensities were used to create our algorithm. We then demonstrated the performance of the proposed algorithm by examining immunosignatures from patients with Glioblastoma multiformae (GBM), an aggressive form of brain cancer. Eight different frameshift targets were identified from the random-sequence peptides using this technique. If immune-reactive antigens can be identified using a relatively simple immune assay, it might enable a diagnostic test with sufficient sensitivity to detect tumors in a clinically useful way.

Created2015-06-18
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Description

Cubic (space group: Fmm) iridium phosphide, Ir2P, has been synthesized at high pressure and high temperature. Angle-dispersive synchrotron X-ray diffraction measurements on Ir2P powder using a diamond-anvil cell at room temperature and high pressures (up to 40.6 GPa) yielded a bulk modulus of B[subscript 0] = 306(6) GPa and its pressure derivative B0′ = 6.4(5).

Cubic (space group: Fmm) iridium phosphide, Ir2P, has been synthesized at high pressure and high temperature. Angle-dispersive synchrotron X-ray diffraction measurements on Ir2P powder using a diamond-anvil cell at room temperature and high pressures (up to 40.6 GPa) yielded a bulk modulus of B[subscript 0] = 306(6) GPa and its pressure derivative B0′ = 6.4(5). Such a high bulk modulus attributed to the short and strongly covalent Ir-P bonds as revealed by first – principles calculations and three-dimensionally distributed [IrP4] tetrahedron network. Indentation testing on a well–sintered polycrystalline sample yielded the hardness of 11.8(4) GPa. Relatively low shear modulus of ~64 GPa from theoretical calculations suggests a complicated overall bonding in Ir2P with metallic, ionic, and covalent characteristics. In addition, a spin glass behavior is indicated by magnetic susceptibility measurements.

ContributorsWang, Pei (Author) / Wang, Yonggang (Author) / Wang, Liping (Author) / Zhang, Xinyu (Author) / Yu, Xiaohui (Author) / Zhu, Jinlong (Author) / Wang, Shanmin (Author) / Qin, Jiaqian (Author) / Leinenweber, Kurt (Author) / Chen, Haihua (Author) / He, Duanwei (Author) / Zhao, Yusheng (Author) / Department of Chemistry and Biochemistry (Contributor)
Created2016-02-24
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Description

Background: High-throughput technologies such as DNA, RNA, protein, antibody and peptide microarrays are often used to examine differences across drug treatments, diseases, transgenic animals, and others. Typically one trains a classification system by gathering large amounts of probe-level data, selecting informative features, and classifies test samples using a small number of

Background: High-throughput technologies such as DNA, RNA, protein, antibody and peptide microarrays are often used to examine differences across drug treatments, diseases, transgenic animals, and others. Typically one trains a classification system by gathering large amounts of probe-level data, selecting informative features, and classifies test samples using a small number of features. As new microarrays are invented, classification systems that worked well for other array types may not be ideal. Expression microarrays, arguably one of the most prevalent array types, have been used for years to help develop classification algorithms. Many biological assumptions are built into classifiers that were designed for these types of data. One of the more problematic is the assumption of independence, both at the probe level and again at the biological level. Probes for RNA transcripts are designed to bind single transcripts. At the biological level, many genes have dependencies across transcriptional pathways where co-regulation of transcriptional units may make many genes appear as being completely dependent. Thus, algorithms that perform well for gene expression data may not be suitable when other technologies with different binding characteristics exist. The immunosignaturing microarray is based on complex mixtures of antibodies binding to arrays of random sequence peptides. It relies on many-to-many binding of antibodies to the random sequence peptides. Each peptide can bind multiple antibodies and each antibody can bind multiple peptides. This technology has been shown to be highly reproducible and appears promising for diagnosing a variety of disease states. However, it is not clear what is the optimal classification algorithm for analyzing this new type of data.

Results: We characterized several classification algorithms to analyze immunosignaturing data. We selected several datasets that range from easy to difficult to classify, from simple monoclonal binding to complex binding patterns in asthma patients. We then classified the biological samples using 17 different classification algorithms. Using a wide variety of assessment criteria, we found ‘Naïve Bayes’ far more useful than other widely used methods due to its simplicity, robustness, speed and accuracy.

Conclusions: ‘Naïve Bayes’ algorithm appears to accommodate the complex patterns hidden within multilayered immunosignaturing microarray data due to its fundamental mathematical properties.

ContributorsKukreja, Muskan (Author) / Johnston, Stephen (Author) / Stafford, Phillip (Author) / Biodesign Institute (Contributor)
Created2012-06-21
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Description

We have previously shown that the diversity of antibodies in an individual can be displayed on chips on which 130,000 peptides chosen from random sequence space have been synthesized. This immunosignature technology is unbiased in displaying antibody diversity relative to natural sequence space, and has been shown to have diagnostic

We have previously shown that the diversity of antibodies in an individual can be displayed on chips on which 130,000 peptides chosen from random sequence space have been synthesized. This immunosignature technology is unbiased in displaying antibody diversity relative to natural sequence space, and has been shown to have diagnostic and prognostic potential for a wide variety of diseases and vaccines. Here we show that a global measure such as Shannon’s entropy can be calculated for each immunosignature. The immune entropy was measured across a diverse set of 800 people and in 5 individuals over 3 months. The immune entropy is affected by some population characteristics and varies widely across individuals. We find that people with infections or breast cancer, generally have higher entropy values than non-diseased individuals. We propose that the immune entropy as measured from immunosignatures may be a simple method to monitor health in individuals and populations.

ContributorsWang, Lu (Author) / Whittemore, K. (Author) / Johnston, Stephen (Author) / Stafford, Phillip (Author) / Biodesign Institute (Contributor)
Created2017-12-22
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Description

We numerically demonstrate a switchable metamaterial absorber/emitter by thermally turning on or off the excitation of magnetic resonance upon the phase transition of vanadium dioxide (VO2). Perfect absorption peak exists around the wavelength of 5 lm when the excitation of magnetic resonance is supported with the insulating VO2 spacer layer.

We numerically demonstrate a switchable metamaterial absorber/emitter by thermally turning on or off the excitation of magnetic resonance upon the phase transition of vanadium dioxide (VO2). Perfect absorption peak exists around the wavelength of 5 lm when the excitation of magnetic resonance is supported with the insulating VO2 spacer layer. The wavelength-selective absorption is switched off when the magnetic resonance is disabled with metallic VO2 that shorts the top and bottom metallic structures. The resonance wavelength can be tuned with different geometry, and the switchable metamaterial exhibits diffuse behaviors at oblique angles. The results would facilitate the design of switchable metamaterials for active control in energy and sensing applications.

ContributorsWang, Hao (Author) / Wang, Yue (Author) / Wang, Liping (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-08-19
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Description

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1, HSP27, GPX1, XRCC1, BAG-1, HHR23A, FAP48, and C-FOS. No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight.

ContributorsBarrila, Jennifer (Author) / Ott, C. Mark (Author) / LeBlanc, Carly (Author) / Mehta, Satish K. (Author) / Crabbe, Aurelie (Author) / Stafford, Phillip (Author) / Pierson, Duane L. (Author) / Nickerson, Cheryl (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2016-12-08
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Description

Recently, near-field thermal radiation has attracted much attention in several fields since it can exceed the Planck blackbody limit through the coupling of evanescent waves. In this work, near-field radiative heat transfer between two semi-infinite dual uniaxial electromagnetic metamaterials with two different material property sets is theoretically analyzed. The near-field

Recently, near-field thermal radiation has attracted much attention in several fields since it can exceed the Planck blackbody limit through the coupling of evanescent waves. In this work, near-field radiative heat transfer between two semi-infinite dual uniaxial electromagnetic metamaterials with two different material property sets is theoretically analyzed. The near-field radiative heat transfer is calculated using fluctuational electrodynamics incorporated with anisotropic wave optics. The underlying mechanisms, namely, magnetic hyperbolic mode, magnetic surface polariton, electrical hyperbolic mode, and electrical surface polariton, between two homogeneous dual uniaxial electromagnetic metamaterials are investigated by examining the transmission coefficient and the spectral heat flux. The effect of vacuum gap distance is also studied, which shows that the enhancement at smaller vacuum gap is mainly due to hyperbolic mode and surface plasmon polariton modes. In addition, the results show that the contribution of s-polarized waves is significant and should not be excluded due to the strong magnetic response regardless of vacuum gap distances. The fundamental understanding and insights obtained here will facilitate the finding and application of novel materials for near-field thermal radiation.

ContributorsChang, Jui-Yung (Author) / Basu, Soumyadipta (Author) / Yang, Yue (Author) / Wang, Liping (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-06-07
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Description

There is an increasing awareness that health care must move from post-symptomatic treatment to presymptomatic intervention. An ideal system would allow regular inexpensive monitoring of health status using circulating antibodies to report on health fluctuations. Recently, we demonstrated that peptide microarrays can do this through antibody signatures (immunosignatures). Unfortunately, printed

There is an increasing awareness that health care must move from post-symptomatic treatment to presymptomatic intervention. An ideal system would allow regular inexpensive monitoring of health status using circulating antibodies to report on health fluctuations. Recently, we demonstrated that peptide microarrays can do this through antibody signatures (immunosignatures). Unfortunately, printed microarrays are not scalable. Here we demonstrate a platform based on fabricating microarrays (~10 M peptides per slide, 330,000 peptides per assay) on silicon wafers using equipment common to semiconductor manufacturing. The potential of these microarrays for comprehensive health monitoring is verified through the simultaneous detection and classification of six different infectious diseases and six different cancers. Besides diagnostics, these high-density peptide chips have numerous other applications both in health care and elsewhere.

ContributorsLegutki, Joseph Barten (Author) / Zhao, Zhan-Gong (Author) / Greving, Matt (Author) / Woodbury, Neal (Author) / Johnston, Stephen (Author) / Stafford, Phillip (Author) / Biodesign Institute (Contributor)
Created2014-09-03
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Description

In this work, we report the design of a wavelength-tunable infrared metamaterial by tailoring magnetic resonance condition with the phase transition of vanadium dioxide (VO2). Numerical simulation based on the finite-difference time-domain method shows a broad absorption peak at the wavelength of 10.9 μm when VO2 is a metal, but it

In this work, we report the design of a wavelength-tunable infrared metamaterial by tailoring magnetic resonance condition with the phase transition of vanadium dioxide (VO2). Numerical simulation based on the finite-difference time-domain method shows a broad absorption peak at the wavelength of 10.9 μm when VO2 is a metal, but it shifts to 15.1 μm when VO2 changes to dielectric phase below its phase transition temperature of 68 °C. The large tunability of 38.5% in the resonance wavelength stems from the different excitation conditions of magnetic resonance mediated by plasmon in metallic VO2 but optical phonons in dielectric VO2. The physical mechanism is elucidated with the aid of electromagnetic field distribution at the resonance wavelengths. A hybrid magnetic resonance mode due to the plasmon-phonon coupling is also discussed. The results here would be beneficial for active control of thermal radiation in novel electronic, optical, and thermal devices.

ContributorsWang, Hao (Author) / Yang, Yue (Author) / Wang, Liping (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-09-28
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Description

In this work, a selective solar absorber made of nanostructured titanium gratings deposited on an ultrathin MgF2 spacer and a tungsten ground film is proposed and experimentally demonstrated. Normal absorptance of the fabricated solar absorber is characterized to be higher than 0.9 in the UV, visible and, near infrared (IR)

In this work, a selective solar absorber made of nanostructured titanium gratings deposited on an ultrathin MgF2 spacer and a tungsten ground film is proposed and experimentally demonstrated. Normal absorptance of the fabricated solar absorber is characterized to be higher than 0.9 in the UV, visible and, near infrared (IR) regime, while the mid-IR emittance is around 0.2. The high broadband absorption in the solar spectrum is realized by the excitation of surface plasmon and magnetic polariton resonances, while the low mid-IR emittance is due to the highly reflective nature of the metallic components. Further directional and polarized reflectance measurements show wide-angle and polarization-insensitive high absorption within solar spectrum. Temperature-dependent spectroscopic characterization indicates that the optical properties barely change at elevated temperatures up to 350 °C. The solar-to-heat conversion efficiency with the fabricated metamaterial solar absorber is predicted to be 78% at 100 °C without optical concentration or 80% at 400 °C with 25 suns. The performance could be further improved with better fabrication processes and geometric optimization during metamaterial design. The strong spectral selectivity, favorable diffuse-like behavior, and good thermal stability make the metamaterial selective absorber promising for significantly enhancing solar thermal energy harvesting in various systems at mid to high temperatures.

ContributorsWang, Hao (Author) / Sivan, Vijay Prasad (Author) / Mitchell, Arnan (Author) / Rosengarten, Gary (Author) / Phelan, Patrick (Author) / Wang, Liping (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-06-01