96 results on '"M. Larijani"'
Search Results
2. Investigation of injection-locked ring oscillators for process, voltage, and temperature-aware low phase-noise reference clock generation.
- Author
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Mohammad M. Larijani and Mohsen Jalali
- Published
- 2022
- Full Text
- View/download PDF
3. Simulation of a Novel Dosimeter Based on Electrical Characteristics of Polymethyl Methacrylate- Carbon Nanotube Composite
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F Ziaie, Sh Malekie, and M M. Larijani
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simulation ,active dosimeter ,composite ,carbon nanotube ,polymethyl methacrylate ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Combination of carbon nanotubes with polymers in an especial weight percentage called electrical percolation threshold, leads to a sudden increase of several orders of magnitude of the electrical conductivity of the polymer-carbon nanotube composite. In the present research, considering these characteristics, the idea of using Polymethyl Methacrylate-Carbon Nanotube composite as an active dosimeter is exhibited. One of the factors affecting the response of this type of dosimeter is the variation of electrical resistance in the composite due to absorption of radiation. For investigation of dosimetric parameters of this composite in different dose rates, the COMSOL software and finite element method were utilized. In this simulation, the electrical current density of PMMA-CNT composite with a thickness of 10µm under a constant voltage of 3 V in different dose rates for 2 min was calculated for the samples having different weight percentages of carbon nanotubes adjacent to the electrical percolation threshold region, namely 0.17, 0.19 and 0.30. The value of the absorbed dose was calculated through the product of the dose rate by the irradiation time. Linearity of the dose response in the range of 400 mGy to ~3 Gy in the diagnostic and therapeutic dose levels could be considered as a positive factor for dosimetry applications of this composite material.
- Published
- 2017
4. A 2-bit/step SAR ADC structure with one radix-4 DAC.
- Author
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M. H. M. Larijani and M. B. Ghaznavi-Ghoushchi
- Published
- 2012
- Full Text
- View/download PDF
5. Effect of Cu Content on TiN-Cu Nanocomposite Film Properties: Structural and Hardness Studies
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M. M. Larijani, P. Balashabadi, H. Seyedi, and E. Jafari-.Khamse
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Nanocomposite ,Thin film ,Soft phase ,Chemical technology ,TP1-1185 - Abstract
Titanium nitride-Copper (TiN-Cu) nanocomposite films were deposited onto stainless steel substrate using hollow cathode discharge ion plating technique. The influence of Cu content in the range of 2-7 at.% on the microstructure, morphology and mechanical properties of deposited films were investigated. Structural properties of the films were studied by X-ray diffraction pattern. Topography of the deposited films was studied using atomic force microscopy. Film hardness was estimated by a triboscope nanoindentation system. However, X-ray photoelectron spectroscopy analysis was performed to study the surface chemical bonding states. It was found that addition of soft Cu phase above 2 at.% to TiN film drastically decreased the film hardness from 30 to 2.8 Gpa due to lubricant effect of segregated copper particles. X-ray photoelectron spectroscopy results showed that Cu and TiN phases grew separately. In our case,the formation of a solid solution or chemical bonding between Cu and Ti was rejected.
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- 2013
- Full Text
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6. The role of Cu content on the structural properties and hardness of TiN –Cu nanocomposite film
- Author
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H. Seyedi, E. Jafari-Khamse, M. M. Larijani, and P. Balashabadi
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010302 applied physics ,Materials science ,Nanocomposite ,Scanning electron microscope ,Mechanical Engineering ,Ion plating ,Metallurgy ,Metals and Alloys ,chemistry.chemical_element ,02 engineering and technology ,Nanoindentation ,021001 nanoscience & nanotechnology ,Microstructure ,01 natural sciences ,X-ray photoelectron spectroscopy ,Chemical engineering ,chemistry ,Mechanics of Materials ,0103 physical sciences ,Materials Chemistry ,Thin film ,0210 nano-technology ,Tin - Abstract
TiN-Cu Nanocomposite coatings with different Cu contents were prepared by co-deposition in a hollow cathode discharge ion plating system. The influence of Cu content in the range of 2–7 at.% on the microstructure, morphology and mechanical properties of the deposited films were investigated. Structural properties of the films were studied by X-ray diffraction pattern (XRD). The composition and morphology of the coatings were characterized using energy dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM), respectively. Atomic force microscopy (AFM) and nanoindentation were used to study topography and mechanical properties of deposited films, respectively. In addition, X-ray photoelectron spectroscopy (XPS) analysis was performed to study the surface chemical bonding states. It was found that Cu and TiN phases grew separately and formation of Cu-N bond or Ti-Cu-N ternary phase was not detected in this study. Moreover, it was shown that addition of the soft Cu phase to TiN film above 2 at.% drastically decreased the film hardness from 30 to 2.8 GPa due to lubricant effect of segregated Cu particles.
- Published
- 2017
7. Hydrogen irradiation on TiO2 nano-thin films
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M. Mahjour-Shafiei, Sh. Heidari, Mohammad Reza Mohammadizadeh, M. Malek, and M. M. Larijani
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Anatase ,Materials science ,Absorption spectroscopy ,Scanning electron microscope ,Band gap ,business.industry ,Analytical chemistry ,General Chemistry ,Fluence ,chemistry.chemical_compound ,Optics ,chemistry ,Titanium dioxide ,General Materials Science ,Irradiation ,Thin film ,business - Abstract
Titanium dioxide thin films were coated on soda-lime glass substrates using spray pyrolysis method with a thickness of 152 ± 10 nm. The films were irradiated with hydrogen ions at room temperature at various beam energies and fluences. Optimized incident beam energy and beam fluence were obtained to improve photocatalytic and hydrophilicity properties of TiO2 thin films by narrowing the band gap. Samples were characterized by scanning electron microscopy to study the surface morphology and by UV–Vis absorption spectroscopy to measure the band gap. The optical band gap of H-doped anatase TiO2 thin films irradiated with hydrogen beam with energies of 2 and 4 keV and a fluence of 1015 ions/cm2 was narrowed from 3.34 eV (before irradiation) to 3.04 and 2.92 eV (after irradiation), respectively. The irradiated sample with energy of 4 keV with a fluence of 1015 ions/cm2 has the best improvement. This is attributed to the contraction of the band gap and to the increase in surface active site. Furthermore, it was observed that photocatalytic and hydrophilicity properties of this sample were improved, as well.
- Published
- 2015
8. Influence of ion dose on nanostructure morphology and electrical properties of nitrogen implanted‐annealed copper
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Anousheh Kazemeini-Asl, Vahid Fathollahi, and Majdid M. Larijani
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Materials science ,Scanning electron microscope ,Biomedical Engineering ,Analytical chemistry ,chemistry.chemical_element ,Bioengineering ,Sputter deposition ,Nitride ,Condensed Matter Physics ,Copper ,Crystallography ,Ion implantation ,chemistry ,X-ray crystallography ,General Materials Science ,Thin film ,Sheet resistance - Abstract
Cu thin films sputter-coated on single crystals of silicon were implanted with 30 keV nitrogen ions under various doses from 1.9 × 1017 to 5.7 × 1017 ions/cm2. The prepared samples were subsequently annealed in nitrogen atmosphere. The grazing incidence X-ray diffraction analysis revealed that in addition to the crystalline copper nitride phase, copper azides were developed by nitrogen ion implantation. With an increase of the implantation dose to 2.3 × 1018 ions/cm2, much of the Cu film was transformed to the crystalline Cu3N phase. Furthermore, the effect of nitrogen ion implantation on Cu thin films under various doses was investigated. The structural properties, morphology and sheet resistance of samples were investigated by grazing incidence X-ray diffraction, atomic force microscopy, field emission scanning electron microscopy and four-point probe techniques, respectively. In addition, the dependence of resistivity of the implanted samples on the implantation dose as well as structural properties is discussed.
- Published
- 2014
9. Temperature dependence of the optical properties of ion-beam sputtered ZrN films
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M. Kiani, V. Fathollahi, M. M. Larijani, and E. Jafari-Khamse
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Range (particle radiation) ,Materials science ,Ion beam ,business.industry ,Analytical chemistry ,Spectral density ,General Chemistry ,Substrate (electronics) ,Zirconium nitride ,chemistry.chemical_compound ,chemistry ,Electrical resistivity and conductivity ,Optoelectronics ,General Materials Science ,business ,Electron scattering ,Plasmon - Abstract
The reflectivity of sputtered Zirconium nitride films on glass substrate has been investigated in the spectral energy range of 0.8–6.1 eV as a function of deposition temperature varying between 373 and 723 K. Optical constants of the prepared films have been determined using the Drude analysis. Experimental results showed strong dependency of optical properties of the films, such as optical resistivity on the substrate temperature. The temperature increase of the substrate has shown an increase in both the plasmon frequency and electron scattering time. The electrical behavior of the films showed a good agreement between their optical and electrical resistivity.
- Published
- 2014
10. Influence of Energy Nitrogen Ion Implantation on Structural and Mechanical Properties of Chromium Thin Film
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B. Banagar, M. Manouchehrian, and M. M. Larijani
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Materials science ,Metallurgy ,technology, industry, and agriculture ,chemistry.chemical_element ,Surfaces and Interfaces ,Indentation hardness ,Grain size ,Surfaces, Coatings and Films ,Abrasion (geology) ,Ion ,Chromium ,Ion implantation ,chemistry ,Mechanics of Materials ,Surface roughness ,Thin film ,Composite material - Abstract
Chromium thin films were deposited on 304 stainless steel using the hollow cathode discharge (HCD) method. Chromium films were implanted with nitrogen ions at different energies ((15-25-35-45) keV) and at a dose of 5×10 17 ions/cm 2 . The implanted films were characterized using x-ray diffraction (XRD), atomic force microscopy (AFM), microhardness testing, friction coefficient measurements, and wear mechanism study. The XRD results confirmed that increasing energy does not effect the formation of the CrN phase. AFM images showed that surface roughness changed proportionally to grain size after implantation. It was found that hardness increased as energy increased. From the friction coefficient measurement, it could be inferred that the friction coefficient decreased as energy increased. The wear mechanism for the un-implanted sample was abrasion, but it shifted to delamination and adhesive as energy increased.
- Published
- 2014
11. Effect of Thickness on the Structural Properties of Tellurium Film Prepared by Thermal Evaporation
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M. Manouchehrian, M. M. Larijani, and M. A. Moghri Moazzen
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Thermal evaporation ,Raman spectroscopy ,lcsh:TP1-1185 ,Tellurium ,lcsh:Chemical technology ,RBS - Abstract
In this research, tellurium (Te) film with thicknesses of 100-250 nm were deposited on ceramic substrates by thermal evaporation at 373 K. The thickness of the film was determined by Rutherford backscattering spectroscopy. The influence of the thickness on the structural, morphological and molecular bonds was characterized using XRD, scanning electron microscope, and Raman spectroscopy. The XRD results confirmed that increasing the thickness, increased the intensity of the peaks, indicating increased crystallinity. SEM images indicated that the density of the film and holes in the film decreased as thickness increased. The Raman spectrum revealed that the TeO2 molecular bond formed on the surface only at room temperature up to 100 nm in thickness; as thickness increased, this bond was observed at 323 K.
- Published
- 2013
12. Effect of aligned carbon nanotubes on electrical conductivity behaviour in polycarbonate matrix
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M Asadi, E J Khamse, M M Larijani, and Z Asadollahi
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Materials science ,Nanocomposite ,Carbon nanotube actuators ,Mechanical properties of carbon nanotubes ,Carbon nanotube ,law.invention ,Carbon nanotube metal matrix composites ,Optical properties of carbon nanotubes ,Condensed Matter::Materials Science ,Mechanics of Materials ,law ,visual_art ,Electric field ,visual_art.visual_art_medium ,General Materials Science ,Polycarbonate ,Composite material - Abstract
This article reports effects of alignment of embedded carbon nanotubes in a polycarbonate polymer matrix under magnetic, direct and alternating current electric fields on the electrical properties of the resulting nanocomposites. Composites consisting of different quantities of carbon nanotubes in a polycarbonate matrix have been prepared using a solution casting technique. The effects of field strength and nanotube concentration on the resulted network structure and conductivity of the composites were studied by in situ optical microscopy, transmission electron microscopy and four-point probe technique. The results showed that the composites prepared in the presence of field had better conductivity than those of as-prepared composites. It was also concluded that the application of alternating current electric field and magnetic field in this system led to the formation of relatively continuing networks while direct current electric field only prevented agglomeration of the carbon nanotubes in the polycarbonate matrix and created relatively uniform distribution of nanotubes in the matrix.
- Published
- 2012
13. Characterization of ion beam sputtered ZrN coatings prepared at different substrate temperatures
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M. Kiani, M. Tanhayi, M. M. Larijani, and A. Majdabadi
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Diffraction ,Materials science ,Ion beam ,Analytical chemistry ,General Chemistry ,Zirconium nitride ,Substrate (electronics) ,engineering.material ,Condensed Matter Physics ,chemistry.chemical_compound ,Coating ,chemistry ,Electrical resistivity and conductivity ,Sputtering ,engineering ,General Materials Science ,Beam (structure) - Abstract
Zirconium nitride (ZrN) coatings were prepared on Si (100) by single ion beam sputtering in N2 and Ar mixture at different substrate temperatures. Structure and morphology of the ZrN coatings were analyzed using X-ray diffraction and atomic force microscopy. Rutherford backscattering technique was utilized for the determination of composition and thickness of the coatings. Electrical properties of the ZrN coatings were determined by four point- probe and Hall test. The results showed that the growth of ZrN with a preferred (111) orientation was achieved. The coating thickness depended on the substrate temperature and coating surface roughly remained smooth. The resistivity of the coatings varied from 1× 10-3 to 14× 10-3 Ω cm depending on the substrate temperature. A correlation between resistivity and charge carrier density was established to explain the electrical behavior of the coatings. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
- Published
- 2011
14. Genetic rearrangements (VDJ/CSR/SHM) (PP-080)
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S. Sakamoto, Y. Pasman, A. Iivanainen, A. Ekman, M. Aida, Y. Shimada, M. Simonet, C. Kano, H. Kuoppamaa, Y. Yu, V. Sievert, J. Wang, M. D. Lange, S. Fagarasan, N. A. Begum, T. He, W. Fu, S. Fujimoto, Y. Agata, L. Huang, D. Jones, M. Nozaki, E. Jouvin-Marche, A. Stanlie, P. Swanson, T. Kina, C. Zhu, T. S. Lim, Z. Yu, R. Lu, M. Larijani, S. K. Singh, E. Dzneladze, O. Hansen, H. Mori, K. Su, M. Ekblom, K. Suzuki, R. Seggewiss, Y. Li, M. Yamashita, T. Nakayama, N. Sakaguchi, A. K. Kaushik, G. X. Liang, K. Kitamura, H. Nagaoka, E. Smith, L. Stenke, R. Shinkura, T. Moritan, Z. Zhang, N. MInato, V. Juvonen, W. Xie, T. Honjo, Z. Konthur, K. M. Marran-Nichol, S. Mustjoki, J. Demongeot, H. Lehrach, S. S. Saini, V. Saridakis, M. Niku, P. N. Marche, S. Kakinuma, M. Nakata, K. Maeda, Z. Wang, K. Masuda, N. Tamaki, A. Cagigi, K. Zhang, I. Yanagihara, T. H. Tran, K. Skriner, M. Muramatsu, Q. Pan-Hammarström, A. Kreutzman, G. E. Wu, K. Porkka, V. Kairisto, J. Liljavirta, J. Huang, R. Ouchida, S. Hong, R. Singh, K. Wakae, F. Thuderoz, C. Rosner, and F. Rubelt
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Immunology ,Immunology and Allergy ,Corporate social responsibility ,General Medicine ,Business ,Computational biology - Published
- 2010
15. Evaluation of a new ionisation chamber fabricated with carbon nanotubes
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Mohammad Ali Ramazanov, K. Arbabi, and M. M. Larijani
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Materials science ,Electrons ,Carbon nanotube ,Catalysis ,law.invention ,Potential applications of carbon nanotubes ,law ,Ionization ,Nanotechnology ,Polymethyl Methacrylate ,Dosimetry ,Radiology, Nuclear Medicine and imaging ,Cobalt Radioisotopes ,Radiometry ,Electrodes ,Ions ,Range (particle radiation) ,Models, Statistical ,Radiation ,Radiological and Ultrasound Technology ,Nanotubes, Carbon ,business.industry ,Carbon nanofiber ,Public Health, Environmental and Occupational Health ,Equipment Design ,General Medicine ,Ionization chamber ,Optoelectronics ,Graphite ,business ,Voltage - Abstract
Ionisation chambers are the most practical and important radiation measurement devices due to their high sensitivity and relatively constant response with wide range of applied potential. In this work, a new plane-parallel ionisation chamber is proposed using carbon nanotubes as sensing electrodes. Some characteristics of the new chamber such as cable effect, leakage current and reproducibility are investigated. The polarisation effects, besides voltage effect and linearity are also verified. All tests are performed using a 60Co gamma radiation source. The obtained results are compared with that of a standard ionisation chamber (PTW Roos W34001 plane-parallel ion chamber) and international code of practice on dosimetry (i.e. IAEA TRS No. 381).
- Published
- 2010
16. The effect of bias voltage on microstructure and hardness of TiN films grown by ion coating deposition
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P. Balashabadi, M. M. Larijani, E. Jafari-Khamse, H. Seyedi, Aliasghar Shokri, and S. Eshghi
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Materials science ,Ion plating ,General Physics and Astronomy ,chemistry.chemical_element ,Biasing ,Substrate (electronics) ,engineering.material ,Microstructure ,Titanium nitride ,chemistry.chemical_compound ,Coating ,chemistry ,engineering ,Composite material ,Thin film ,Tin - Abstract
Titanium nitride (TiN) thin films were grown onto 316 stainless steel substrate at 350 ° C by hollow cathode discharge ion plating technique. Since microstructure and mechanical properties of the samples were strongly affected by bias voltage, different bias voltages from 0 to | − 120| V were applied to the substrate. Rutherford back-scattering spectroscopy showed that the film thickness decreased when the bias voltage increased. X-ray diffraction patterns showed that the as-prepared TiN thin films were preferentially grown in the (200) direction with a satisfactory crystal quality at −30 V. The spatial scaling behavior of the TiN films grown by ion coating have been investigated by using the atomic force microscopy as well as a kinetic roughening model for the film thickness ranging from 380 to 590nm. The roughness and dynamic scaling exponents have been independently measured (α = 0.7 ± 0.05 and Z = 3.03 ± 0.05) and they exhibited a smooth surface growth. Nanohardness showed formation of a film with 30GPa hardness and 285 GPa Young modulus at −30 V bias voltage.
- Published
- 2015
17. Thermoluminescence properties of gamma-irradiated nano-structure hydroxyapatite
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M, Shafaei, F, Ziaie, D, Sardari, and M M, Larijani
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Durapatite ,Luminescence ,Gamma Rays ,Temperature ,Nanostructures - Abstract
The suitability of nano-structured hydroxyapatite (HAP) for use as a thermoluminescence dosimeter was investigated. HAP samples were synthesized using a hydrolysis method. The formation of nanoparticles was confirmed by X-ray diffraction and average particle size was estimated to be ~30 nm. The glow curve exhibited a peak centered at around 200 °C. The additive dose method was applied and this showed that the thermoluminescence (TL) glow curves follow first-order kinetics due to the non-shifting nature of Tm after different doses. The numbers of overlapping peaks and related kinetic parameters were identified from Tm -Tstop through computerized glow curve deconvolution methods. The dependence of the TL responses on radiation dose was studied and a linear dose response up to 1000 Gy was observed for the samples.
- Published
- 2015
18. Immunotargeting and eradication of orthotopic melanoma using a chemokine-enhanced DNA vaccine
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J Lorton, M Larijani, M Farber, Ulrich Rodeck, M Grazzini, Vitali Alexeev, Daria Marley Kemp, Olga Igoucheva, and A Pidich
- Subjects
Skin Neoplasms ,Genetic enhancement ,medicine.medical_treatment ,T-Lymphocytes ,Melanoma, Experimental ,Biology ,Lymphocyte Activation ,Cancer Vaccines ,DNA vaccination ,Mice ,Immune system ,Cell Line, Tumor ,Genetics ,medicine ,Vaccines, DNA ,Cytotoxic T cell ,Animals ,Molecular Biology ,Skin ,Chemokine CCL20 ,Chemokine CCL21 ,Melanoma ,Immunotherapy ,Genetic Therapy ,Vaccine efficacy ,medicine.disease ,Vaccination ,Mice, Inbred C57BL ,Immunology ,Molecular Medicine ,T-Lymphocytes, Cytotoxic - Abstract
DNA vaccines are attractive candidates for tumor immunotherapy. However, the potential of DNA vaccines in treating established malignant lesions has yet to be demonstrated. Here we demonstrate that transient alteration of either intratumoral or intradermal (ID) chemotactic gradients provide a favorable milieu for DNA vaccine-mediated activation of tumor-specific immune response in both prophylactic and therapeutic settings. Specifically, we show that priming of established B16 ID melanoma lesions via forced intratumoral expression of CCL21 boosted DNA vaccination-dependent systemic cytotoxic immune response leading to the regression of tumor nodules. In this setting, application of CCL20 was not effective likely due to the engagement of the regulatory T cells. However, priming of the skin at DNA vaccine administration sites outside the tumor bed with both CCL20 and CCL21 chemokines along with structural modifications of the DNA vaccine significantly improved vaccine efficacy. This optimized ID vaccination regimen led to the inhibition of distant established melanomas and prolonged tumor-free survival of mice observed in 60% of vaccinated animals with complete tumor remission in 30%. These effects were mediated by extranodal priming and activation of T cells at vaccine administration sites and progressive accumulation of systemic antigen-specific cytotoxic T cells (CTLs) on successive vaccinations. These results underscore the potential of chemokine-enhanced DNA vaccination to mount therapeutic immune response against established tumors.
- Published
- 2012
19. Corrosion behavior of solid solution (Ti, Al) N as a function of Al concentration
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H. Seyedi, M. Yari, M. Manouchehrian, and M. M. Larijani
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Materials science ,Metallurgy ,Analytical chemistry ,chemistry.chemical_element ,General Chemistry ,engineering.material ,Condensed Matter Physics ,Indentation hardness ,Cathode ,Corrosion ,law.invention ,Coating ,chemistry ,law ,Phase (matter) ,engineering ,General Materials Science ,Spectroscopy ,Tin ,Solid solution - Abstract
In this work, a series of (Ti, Al) N coatings with different Al contents were deposited on 304 stainless steel substrates by Hollow Cathode Discharge (HCD) method. The coatings were grown on 304 stainless steel substrates at 400 °C. The coatings were characterized using energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), atomic force microscopy (AFM), and microhardness test. The XRD confirmed the transition from TiN phase to (Ti, Al) N phase and then to AlN phase with increasing Al concentration in the solid solution. It was found that with increasing Al concentration the hardness of the coatings initially increased up to a maximum value of about 30 GPa at around 32 at.% of Al and then the coating hardness decreased rapidly with further increase of Al content (Al > 32 at.%). The potentiodynamic polarization analysis was carried out in 3.5 wt.% NaCl solutions to study the corrosion resistance of the coatings. From the corrosion test it can be inferred that the amount of Al atoms in the coatings plays an important role for reducing the corrosion.
- Published
- 2012
20. The effect of oxidation temperature on the nano crystalline structure of ZrO2 films deposited on silicon and glass substrates
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M. M. Larijani, M. Eshghabadi, and D. Najafi
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Thermal oxidation ,Materials science ,Silicon ,Metallurgy ,chemistry.chemical_element ,General Chemistry ,Substrate (electronics) ,Sputter deposition ,Condensed Matter Physics ,Chemical engineering ,chemistry ,Phase (matter) ,General Materials Science ,Crystallite ,Silicon oxide ,Sheet resistance - Abstract
Zirconium oxide (ZrO2) films have been prepared by using ex situ thermal oxidation of sputtered Zr films on glass and silicon substrates. XRD patterns show that a highly monoclinic (111) preferential orientation of ZrO2 phase can be formed with increasing the oxidation temperature. According to XRD patterns in all thermal oxidized samples silicon oxide phase is present as interfacial layer at the Zr (ZrO2) / Si (glass) interface. In the case of silicon substrates, crystallite sizes obtained from ZrO2 peak with higher intensity reveal an increase with substrate temperature. AFM measurement shows on the whole a decrease of average surface roughness with oxidation temperature. The electrical property of the prepared films is investigated by means of four point probe measurement. An abrupt increase of sheet resistivity occurs when the crystallinity of ZrO2 phase enhances at higher temperature. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
- Published
- 2011
21. A DC HF CVD process to grow carbon nanostructures (diamond films, nanotubes, nanofibers, …
- Author
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C.S. Cojocaru, M. Larijani, and F. Le Normand
- Published
- 2003
- Full Text
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22. High density nucleation of diamond on a large scale by a DC HF CVD process
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M. Larijani, C.S. Cojocaru, F. Le Normand, J. Hommet, and P. Veis
- Published
- 2003
- Full Text
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23. Differential usage of VH gene segments is mediated by cis elements
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C C, Yu, M, Larijani, I N, Miljanic, and G E, Wu
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Recombination, Genetic ,Reading Frames ,Genes, Immunoglobulin ,Gene Rearrangement, B-Lymphocyte, Heavy Chain ,Immunoglobulin Variable Region ,Regulatory Sequences, Nucleic Acid ,Mice, Inbred C57BL ,Mice ,Gene Frequency ,Immunoglobulin J-Chains ,Sequence Homology, Nucleic Acid ,Animals ,Immunoglobulin Heavy Chains ,Antibody Diversity ,Plasmids ,Sequence Deletion - Abstract
Ig diversity is generated in large part by the combinatorial joining of the Ig gene segments, VH, D, and JH, that together encode the variable domain of Ig. The final Ig repertoire, however, not only reflects the diversity generated through V(D)J recombinatorial joining, but it is also the product of a number of developmental restraints and selections. To avoid such restrictions and assess the recombination potential of individual Ig gene segments, we constructed Ig heavy (H) chain microlocus plasmids, each of which contain germline coding, recombination signal, and flanking sequences of a VH, D, and JH gene segment. These plasmids allow us to assess the recombination potential of the segments in the context of their natural flanking DNA sequences, but in the absence of any higher order chromatin structure or cellular selection. We found that the frequency and extent of deletions and additions at the recombination breakpoints are similar to those observed at rearranged Ig H chain loci in intact animals. The relative frequencies of the types of rearrangements--VD-J, V-DJ, VinvD-J (invD = inverted D), and VDJ--however, differ strongly. Moreover, V81x, the most used VH gene segment in intact mice, also is overused in this plasmid assay, 15 to 30 times that of another VH segment. This result indicates that the overuse of V81x in the early B cell repertoire can be a consequence of its DNA sequence and not of cellular activities.
- Published
- 1998
24. Distinct stage-specific cis-active transcriptional mechanisms control expression of T cell coreceptor CD8 alpha at double- and single-positive stages of thymic development
- Author
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X L, Zhang, R, Seong, R, Piracha, M, Larijani, M, Heeney, J R, Parnes, and J W, Chamberlain
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Mice, Knockout ,Transcription, Genetic ,CD8 Antigens ,Receptors, Antigen, T-Cell, alpha-beta ,Receptors, Antigen, T-Cell ,Gene Expression Regulation, Developmental ,Nucleic Acid Hybridization ,Cell Differentiation ,Mice, Inbred Strains ,Mice, Transgenic ,Thymus Gland ,Flow Cytometry ,Mice, Inbred C57BL ,Mice ,Mutagenesis, Insertional ,Organ Specificity ,T-Lymphocyte Subsets ,Animals ,Antigens, Ly ,Humans ,Cell Lineage ,Transgenes - Abstract
Developing thymocytes that give rise to CD8+ (cytotoxic) and CD4+ (helper) alpha beta-TCR T lymphocytes go through progressive stages of expression of coreceptors CD8 and CD4 from being negative for both (the double-negative stage), to coexpressing both (the double-positive (DP) stage), to a mutually exclusive sublineage-specific expression of one or the other (the single-positive (SP) stage). To delineate the mechanisms underlying regulation of CD8 during these developmental transitions, we have examined expression of a series of mouse CD8 alpha gene constructs in developing T cells of conventional and CD8 alpha "knock-out" transgenic mice. Our results indicate that cis-active transcriptional control sequences essential for stage- and sublineage-specific expression lie within a 5' 40-kb segment of the CD8 locus, approximately 12 kb upstream of the CD8 alpha gene. Studies to characterize and sublocalize these cis sequences showed that a 17-kb 5' subfragment is able to direct expression of the CD8 alpha gene up to the CD3intermediate DP stage but not in more mature DP or SP cells. These results indicate that stage-specific expression of CD8 alpha in developing T cells is mediated by the differential activity of multiple functionally distinct cis-active transcriptional control mechanisms. It will be important to determine the relationship of "switching" between these cis mechanisms and selection.
- Published
- 1998
25. Study of carbon concentration on the nanostructural and corrosion properties of Zr(C, N)/ss304 films
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M. Ghorannevis, M. Yari, M. M. Larijani, M. Alijannejad, and M. B. Zanjanbar
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Materials science ,Argon ,Scanning electron microscope ,Metallurgy ,Analytical chemistry ,chemistry.chemical_element ,Condensed Matter Physics ,Electrochemistry ,Grain size ,Electronic, Optical and Magnetic Materials ,Corrosion ,chemistry ,Phase (matter) ,Instrumentation ,Carbon ,Stoichiometry - Abstract
The improvement of corrosion resistance of ZrN 1- x C x films (0 ≤ x ≤ 1) on AISI stainless steel (ss) 304 is studied as a function of methane flow rate introduced into mixture of argon and nitrogen gases (Ar + N 2 ). The films were deposited using ion beam sputtering technique at 400 °C and their corrosion resistance has been investigated via electrochemical test using 0.5 M H 2 SO 4 solution. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were performed to study the micro and nano-structures of the films. Film stoichiometry was determined by Rutherford backscattering (RBS) technique using SIMNRA code. An average grain size of 7 nm was calculated for deposited films using Scherrer's formula. X-ray diffraction results showed the presence of a transition crystalline phase from ZrN to ZrC phase corresponding to the formation of ZrN 1- x C x crystalline phase. The electrochemical test revealed that the film corrosion resistance increased with increasing x values. Furthermore, micrographs obtained by SEM did not indicate any damage on the sample surface due to corrosive agent attacks for x > 0.6.
- Published
- 2010
26. Visible light photo-induced antibacterial activity of CNT–doped TiO2 thin films with various CNT contents
- Author
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Rouhollah Azimirad, Omid Akhavan, S. Safa, and M. M. Larijani
- Subjects
Anatase ,Materials science ,business.industry ,Band gap ,Doping ,General Chemistry ,Carbon nanotube ,law.invention ,Post annealing ,Chemical engineering ,law ,Materials Chemistry ,Optoelectronics ,Thin film ,business ,Antibacterial activity ,Visible spectrum - Abstract
Carbon nanotube (CNT)-doped TiO2 thin films with various CNT contents were synthesized by sol–gel method for visible light photoinactivation of Escherichia coli bacteria. Post annealing of the CNT–doped TiO2 thin films at 450 °C resulted in anatase TiO2 and formation of Ti–C and Ti–O–C carbonaceous bonds in the film. By increasing the CNT content, the thin films could further inactivate the bacteria in the dark. Meanwhile, as the CNT content increased from zero to 40 wt% the effective optical band gap energy of the CNT–doped TiO2 thin films annealed at 450 °C decreased from 3.2–3.3 to less than ∼2.8 eV providing light absorption in the visible region. Concerning this, visible light photoinactivation of the bacteria on the surface of the films was found to be optimum for 20 wt% CNT content. The CNT–doped TiO2 thin films annealed at 450 °C showed a further improved photoinactivation of bacteria than the films annealed at 100 °C. The improvement in the visible light photocatalytic performance was assigned to the charge transfer through the carbonaceous bonds formed between the TiO2 and the CNT content of the films annealed at 450 °C, in contrast to the thin films annealed at 100 °C which contained no such effective bonds.
- Published
- 2010
27. Effects of Contents of Multiwall Carbon Nanotubes in Polyaniline Films on Optical and Electrical Properties of Polyaniline.
- Author
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N. Bafandeh, M. M. Larijani, A. Shafiekhani, M. R. Hantehzadeh, and N. Sheikh
- Subjects
- *
MULTIWALLED carbon nanotubes , *POLYANILINES , *OPTICAL properties , *ELECTRIC properties of solids , *SCANNING electron microscopy - Abstract
We investigate the effects of different contents of multiwall carbon nanotubes (MWCNTs) on optical and electrical properties of polyaniline (PANI). The MWCNTs/PANI composites are deposited on glass substrates coated with indium tin oxide (ITO) by the spin-coating technique. The scanning electron microscopy shows that nanotubes are coated with the PANI layer and x-ray diffraction patterns show that all deposited composite films have an amorphous character. The analysis of a UV-vis spectrophotometer indicates the blue shift of the absorbance peak and a decrease in optical band gap value by the enhancement of the CNT content in the PANI matrix while the Urbach energy increases. The Raman spectrum shows the blue shift 1404→1417 cm−1 and photoluminescence spectra show an increase in the intensity of characteristic PANI peak at 436 nm with the increasing CNT content. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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28. Human and bats genome robustness under COSMIC mutational signatures.
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Song JH, Zeng Y, Dávalos LM, MacCarthy T, Larijani M, and Damaghi M
- Abstract
Carcinogenesis is an evolutionary process, and mutations can fix the selected phenotypes in selective microenvironments. Both normal and neoplastic cells are robust to the mutational stressors in the microenvironment to the extent that secure their fitness. To test the robustness of genes under a range of mutagens, we developed a sequential mutation simulator, Sinabro, to simulate single base substitution under a given mutational process. Then, we developed a pipeline to measure the robustness of genes and cells under those mutagenesis processes. We discovered significant human genome robustness to the APOBEC mutational signature SBS2, which is associated with viral defense mechanisms and is implicated in cancer. Robustness evaluations across over 70,000 sequences against 41 signatures showed higher resilience under signatures predominantly causing C-to-T (G-to-A) mutations. Principal component analysis indicates the GC content at the codon's wobble position significantly influences robustness, with increased resilience noted under transition mutations compared to transversions. Then, we tested our results in bats at extremes of the lifespan-to-mass relationship and found the long-lived bat is more robust to APOBEC than the short-lived one. By revealing robustness to APOBEC ranked highest in human (and bats with much more than number of APOBEC) genome, this work bolsters the key potential role of APOBECs in aging and cancer, as well as evolved countermeasures to this innate mutagenic process. It also provides the baseline of the human and bat genome robustness under mutational processes associated with aging and cancer.
- Published
- 2024
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29. Redefining high risk multiple myeloma with an APOBEC/Inflammation-based classifier.
- Author
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Grasedieck S, Panahi A, Jarvis MC, Borzooee F, Harris RS, Larijani M, Avet-Loiseau H, Samur M, Munshi N, Song K, Rouhi A, and Kuchenbauer F
- Subjects
- Humans, APOBEC Deaminases genetics, Biomarkers, Tumor, Prognosis, Multiple Myeloma pathology, Multiple Myeloma immunology, Inflammation pathology
- Published
- 2024
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30. Autosomal recessive congenital ichthyosis due to novel CYP4F22 mutation presenting with a collodion membrane and ocular manifestations.
- Author
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Swink SM, Hurley M, Haynes D, and Larijani M
- Subjects
- Humans, Male, Female, Phenotype, Ichthyosis, Lamellar genetics, Ichthyosis, Lamellar diagnosis, Cytochrome P-450 Enzyme System genetics, Mutation
- Abstract
Autosomal recessive congenital ichthyoses (ARCI) are a range of genetic disorders of keratinization. The rare CYP4F22 gene mutation can present with or without collodion membrane at birth and leads to the development of mild ichthyosis phenotype. We report a case of a novel pathogenic CYP4F22 genetic mutation presenting with collodion membrane and ocular manifestations. Ocular manifestations have recently been reported in a patient with ARCI with known CYP4F22 mutation, which further supports a possible correlation between the CYP4F22 mutation and this distinct phenotype., (© 2024 Wiley Periodicals LLC.)
- Published
- 2024
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31. Targeting APOBECs in cancer: It's about timing.
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Hata AN and Larijani M
- Subjects
- Humans, Mutagenesis, Cytidine Deaminase genetics, APOBEC Deaminases, Neoplasms drug therapy, Neoplasms genetics
- Abstract
APOBEC3 cytidine deaminases have emerged as key drivers of mutagenesis in a wide spectrum of tumor types and are now appreciated to play a causal role in driving tumor evolution and drug resistance. As efforts to develop APOBEC3 inhibitors progress, understanding the timing and consequences of APOBEC3-mediated mutagenesis in distinct clinical contexts will be critical for guiding the development of anti-cancer therapeutic strategies., Competing Interests: Declaration of interests A.N.H. has received grants/research support from Amgen, Blueprint Medicines, BridgeBio, Bristol-Myers Squibb, C4 Therapeutics, Eli Lilly, Novartis, Nuvalent, Pfizer, Roche/Genentech, and Scorpion Therapeutics; has served as a compensated consultant for Amgen, Engine Biosciences, Nuvalent, Oncovalent, Pfizer, TigaTx, and Tolremo Therapeutics., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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32. Evolutionary potential of the monkeypox genome arising from interactions with human APOBEC3 enzymes.
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Delamonica B, Davalos L, Larijani M, Anthony SJ, Liu J, and MacCarthy T
- Abstract
APOBEC3, an enzyme subfamily that plays a role in virus restriction by generating mutations at particular DNA motifs or mutational 'hotspots', can drive viral mutagenesis with host-specific preferential hotspot mutations contributing to pathogen variation. While previous analysis of viral genomes from the 2022 Mpox (formerly Monkeypox) disease outbreak has shown a high frequency of C>T mutations at TC motifs, suggesting recent mutations are human APOBEC3-mediated, how emerging monkeypox virus (MPXV) strains will evolve as a consequence of APOBEC3-mediated mutations remains unknown. By measuring hotspot under-representation, depletion at synonymous sites, and a combination of the two, we analyzed APOBEC3-driven evolution in human poxvirus genomes, finding varying hotspot under-representation patterns. While the native poxvirus molluscum contagiosum exhibits a signature consistent with extensive coevolution with human APOBEC3, including depletion of TC hotspots, variola virus shows an intermediate effect consistent with ongoing evolution at the time of eradication. MPXV, likely the result of recent zoonosis, showed many genes with more TC hotspots than expected by chance (over-representation) and fewer GC hotspots than expected (under-representation). These results suggest the MPXV genome: (1) may have evolved in a host with a particular APOBEC GC hotspot preference, (2) has inverted terminal repeat (ITR) regions-which may be exposed to APOBEC3 for longer during viral replication-and longer genes likely to evolve faster, and therefore (3) has a heightened potential for future human APOBEC3-meditated evolution as the virus spreads in the human population. Our predictions of MPXV mutational potential can both help guide future vaccine development and identification of putative drug targets and add urgency to the task of containing human Mpox disease transmission and uncovering the ecology of the virus in its reservoir host., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)
- Published
- 2023
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33. Atopic dermatitis-like graft-versus-host disease treated with dupilumab.
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Larijani M, Zarowin D, Wohlschlaeger A, Perman MJ, and Treat JR
- Subjects
- Adult, Humans, Child, Quality of Life, Antibodies, Monoclonal, Humanized therapeutic use, Severity of Illness Index, Treatment Outcome, Dermatitis, Atopic drug therapy, Graft vs Host Disease drug therapy
- Abstract
The mainstay of treatment for atopic dermatitis (AD)-like graft-versus-host disease (GVHD) in both pediatric and adult patients includes oral corticosteroids with or without other systemic immunosuppressive therapies. To our knowledge, we report the first case series of dupilumab in the treatment of AD-like GVHD in a pediatric cohort of four patients, where we observed clinical improvement of GVHD as well as a reduction in itch in 3/4 (75%) patients. Our findings suggest that dupilumab is not only effective in treating AD-like GVHD, but also reduces systemic immunosuppression in the pediatric transplant population. The ability to reduce the length and amount of immunosuppression as well as improve quality of life suggest that dupilumab may serve as a safe and effective therapeutic option in our transplant population with GVHD., (© 2022 Wiley Periodicals LLC.)
- Published
- 2023
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34. Ancestral reconstruction reveals catalytic inactivation of activation-induced cytidine deaminase concomitant with cold water adaption in the Gadiformes bony fish.
- Author
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Ghorbani A, Khataeipour SJ, Solbakken MH, Huebert DNG, Khoddami M, Eslamloo K, Collins C, Hori T, Jentoft S, Rise ML, and Larijani M
- Subjects
- Animals, Male, Water, Cytidine Deaminase genetics, Fishes genetics, Vertebrates, Gadiformes
- Abstract
Background: Antibody affinity maturation in vertebrates requires the enzyme activation-induced cytidine deaminase (AID) which initiates secondary antibody diversification by mutating the immunoglobulin loci. AID-driven antibody diversification is conserved across jawed vertebrates since bony and cartilaginous fish. Two exceptions have recently been reported, the Pipefish and Anglerfish, in which the AID-encoding aicda gene has been lost. Both cases are associated with unusual reproductive behavior, including male pregnancy and sexual parasitism. Several cold water fish in the Atlantic cod (Gadinae) family carry an aicda gene that encodes for a full-length enzyme but lack affinity-matured antibodies and rely on antibodies of broad antigenic specificity. Hence, we examined the functionality of their AID., Results: By combining genomics, transcriptomics, immune responsiveness, and functional enzymology of AID from 36 extant species, we demonstrate that AID of that Atlantic cod and related fish have extremely lethargic or no catalytic activity. Through ancestral reconstruction and functional enzymology of 71 AID enzymes, we show that this enzymatic inactivation likely took place relatively recently at the emergence of the true cod family (Gadidae) from their ancestral Gadiformes order. We show that this AID inactivation is not only concordant with the previously shown loss of key adaptive immune genes and expansion of innate and cell-based immune genes in the Gadiformes but is further reflected in the genomes of these fish in the form of loss of AID-favored sequence motifs in their immunoglobulin variable region genes., Conclusions: Recent demonstrations of the loss of the aicda gene in two fish species challenge the paradigm that AID-driven secondary antibody diversification is absolutely conserved in jawed vertebrates. These species have unusual reproductive behaviors forming an evolutionary pressure for a certain loss of immunity to avoid tissue rejection. We report here an instance of catalytic inactivation and functional loss of AID rather than gene loss in a conventionally reproducing vertebrate. Our data suggest that an expanded innate immunity, in addition to lower pathogenic pressures in a cold environment relieved the pressure to maintain robust secondary antibody diversification. We suggest that in this unique scenario, the AID-mediated collateral genome-wide damage would form an evolutionary pressure to lose AID function., (© 2022. The Author(s).)
- Published
- 2022
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35. Multifocal Kaposiform Hemangioendothelioma in a Newborn With Confirmatory Histopathology.
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Cohen OG, Florez-Pollack S, Finn LS, Larijani M, Jen M, Treat J, Adams DM, and Acord MR
- Subjects
- Infant, Newborn, Humans, Endothelial Cells, Kasabach-Merritt Syndrome diagnosis, Kasabach-Merritt Syndrome complications, Hemangioendothelioma diagnosis, Hemangioendothelioma complications, Sarcoma, Kaposi diagnosis, Sarcoma, Kaposi complications
- Abstract
Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor of childhood resulting from abnormal angiogenesis and lymphangiogenesis. Most commonly, KHE presents as a single tissue mass, ranging from an erythematous papule to a violaceous indurated tumor. Definitive diagnosis requires tissue sampling with the demonstration of ill-defined nodules and fascicles of spindle-shaped D2-40 positive endothelial cells, forming slit-like vascular channels. This newborn presented with multifocal cutaneous Kaposiform hemangioendothelioma associated with Kasabach-Merritt phenomenon confirmed on histopathology with immunostaining., (Copyright © 2022 by the American Academy of Pediatrics.)
- Published
- 2022
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- View/download PDF
36. Evaluation of Candida albicans biofilm formation on conventional and computer-aided-design/computer-aided manufacturing (CAD/CAM) denture base materials.
- Author
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Larijani M, Zareshahrabadi Z, Alhavaz A, Hajipour R, Ranjbaran A, Giti R, Soltankarimi V, and Zomorodian K
- Abstract
Background and Purpose: The human mouth mucosal surface is colonized by indigenous microflora, which normally maintains an ecological balance among different species. However, certain environmental or biological factors may disrupt this balance, leading to microbial diseases. Candida albicans biofilms are formed on indwelling medical devices and have an association with both oral and invasive candidiasis. This study aimed to compare the amount of adherent C. albicans and the biofilm formed on different denture base materials. The adhesion of C. albicans to denture base materials is widely recognized as the main reason for the development of denture stomatitis., Materials and Methods: In total, 56 polymethyl methacrylate (PMMA) acrylic resin disc-shaped samples were divided into four groups as follows: 1) chemically polymerized PMMA, 2) heat-polymerized PMMA, 3) computer-aided design and computer-aided manufacturing (CAD/CAM) PMMA in high polish, and 4) CAD/CAM resins in glazed form. The adherent cells and formation of C. albicans strains (562, 1905, 1912, and 1949) biofilm were measured by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method and use of a microplate reader. Moreover, morphological alterations of C. albicans cells were investigated using scanning electron microscopy (SEM)., Results: The biofilm formation was significantly lower on CAD/CAM acrylic resins, compared to conventional denture base materials. The obtained results were confirmed by the SEM images of C. albicans biofilms. CAD/CAM PMMA-based polymers may be preferable to inhibit C. albicans biofilm formation and reduce Candida-associated denture stomatitis in long-term use., Conclusion: Based on the findings, the CAD/CAM technique can be used as an efficient technique for denture fabrication as it inhibits microbial accumulation, and consequently, microbial biofilm., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright: © 2021, Published by Mazandaran University of Medical Sciences on behalf of Iranian Society of Medical Mycology and Invasive Fungi Research Center.)
- Published
- 2022
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- View/download PDF
37. Severe recalcitrant hidradenitis suppurativa in a 2-year-old boy with partial trisomy 13.
- Author
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Keyes E, Larijani M, Castelo-Soccio L, and Treat JR
- Subjects
- Child, Preschool, Hidradenitis Suppurativa diagnosis, Hidradenitis Suppurativa genetics, Hidradenitis Suppurativa therapy, Humans, Immunoglobulins administration & dosage, Immunologic Deficiency Syndromes genetics, Immunologic Deficiency Syndromes therapy, Male, Trisomy 13 Syndrome complications, Chromosomes, Human, Pair 13, Hidradenitis Suppurativa complications, Trisomy, Trisomy 13 Syndrome diagnosis
- Abstract
We report the case of a 2-year-old boy with mosaic trisomy 13 and immunodeficiency who developed severe hidradenitis suppurativa beginning at the age of 18 months. Unresponsive to standard therapies, he exhibited a partial response to immunoglobulin replacement therapy., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
- Full Text
- View/download PDF
38. Cutaneous mastocytosis in a child with a de novo GNB1 mutation.
- Author
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Lattanzio K, Larijani M, and Treat JR
- Subjects
- Child, Humans, Mutation, GTP-Binding Protein beta Subunits genetics, Mastocytosis, Cutaneous complications, Mastocytosis, Cutaneous diagnosis, Mastocytosis, Cutaneous genetics, Neurodevelopmental Disorders, Urticaria Pigmentosa complications
- Abstract
In the last few years, de novo mutations in the GNB1 gene have been found to cause a neurodevelopmental disorder typically characterized by global developmental delay and hypotonia. Only 4 cases of maculopapular cutaneous mastocytosis in children with GNB1 mutations have been reported to date. Here, we describe another case of the condition with concomitant cutaneous mastocytosis., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
- Full Text
- View/download PDF
39. The optimal pH of AID is skewed from that of its catalytic pocket by DNA-binding residues and surface charge.
- Author
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Ghorbani A, King JJ, and Larijani M
- Subjects
- Biocatalysis, Cytidine Deaminase genetics, HEK293 Cells, Humans, Hydrogen-Ion Concentration, Mutagenesis, Point Mutation, Protein Binding, Proteins genetics, Surface Properties, Transfection, Catalytic Domain genetics, Cytidine Deaminase chemistry, Cytidine Deaminase metabolism, DNA, Single-Stranded metabolism, Proteins chemistry, Proteins metabolism, Signal Transduction genetics
- Abstract
Activation-induced cytidine deaminase (AID) is a member of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of cytidine deaminases. AID mutates immunoglobulin loci to initiate secondary antibody diversification. The APOBEC3 (A3) sub-branch mutates viral pathogens in the cytosol and acidic endosomal compartments. Accordingly, AID functions optimally near-neutral pH, while most A3s are acid-adapted (optimal pH 5.5-6.5). To gain a structural understanding for this pH disparity, we constructed high-resolution maps of AID catalytic activity vs pH. We found AID's optimal pH was 7.3 but it retained most (>70%) of the activity at pH 8. Probing of ssDNA-binding residues near the catalytic pocket, key for bending ssDNA into the pocket (e.g. R25) yielded mutants with altered pH preference, corroborating previous findings that the equivalent residue in APOBEC3G (H216) underlies its acidic pH preference. AID from bony fish exhibited more basic optimal pH (pH 7.5-8.1) and several R25-equivalent mutants altered pH preference. Comparison of pH optima across the AID/APOBEC3 family revealed an inverse correlation between positive surface charge and overall catalysis. The paralogue with the most robust catalytic activity (APOBEC3A) has the lowest surface charge and most acidic pH preference, while the paralogue with the most lethargic catalytic rate (AID) has the most positive surface charge and highest optimal pH. We suggest one possible mechanism is through surface charge dictating an overall optimal pH that is different from the optimal pH of the catalytic pocket microenvironment. These findings illuminate an additional structural mechanism that regulates AID/APOBEC3 mutagenesis., (© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
- Published
- 2022
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40. Structure-Based Design of First-Generation Small Molecule Inhibitors Targeting the Catalytic Pockets of AID, APOBEC3A, and APOBEC3B.
- Author
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King JJ, Borzooee F, Im J, Asgharpour M, Ghorbani A, Diamond CP, Fifield H, Berghuis L, and Larijani M
- Abstract
Activation-induced cytidine deaminase (AID) initiates antibody diversification by mutating immunoglobulin loci in B lymphocytes. AID and related APOBEC3 (A3) enzymes also induce genome-wide mutations and lesions implicated in tumorigenesis and tumor progression. The most prevalent mutation signatures across diverse tumor genomes are attributable to the mistargeted mutagenic activities of AID/A3s. Thus, inhibiting AID/A3s has been suggested to be of therapeutic benefit. We previously used a computational-biochemical approach to gain insight into the structure of AID's catalytic pocket, which resulted in the discovery of a novel type of regulatory catalytic pocket closure that regulates AID/A3s that we termed the "Schrodinger's CATalytic pocket". Our findings were subsequently confirmed by direct structural studies. Here, we describe our search for small molecules that target the catalytic pocket of AID. We identified small molecules that inhibit purified AID, AID in cell extracts, and endogenous AID of lymphoma cells. Analogue expansion yielded derivatives with improved potencies. These were found to also inhibit A3A and A3B, the two most tumorigenic siblings of AID. Two compounds exhibit low micromolar IC
50 inhibition of AID and A3A, exhibiting the strongest potency for A3A. Docking suggests key interactions between their warheads and residues lining the catalytic pockets of AID, A3A, and A3B and between the tails and DNA-interacting residues on the surface proximal to the catalytic pocket opening. Accordingly, mutants of these residues decreased inhibition potency. The chemistry and abundance of key stabilizing interactions between the small molecules and residues within and immediately outside the catalytic pockets are promising for therapeutic development., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)- Published
- 2021
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41. Evolutionary Comparative Analyses of DNA-Editing Enzymes of the Immune System: From 5-Dimensional Description of Protein Structures to Immunological Insights and Applications to Protein Engineering.
- Author
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Ghorbani A, Quinlan EM, and Larijani M
- Subjects
- Animals, Humans, Protein Conformation, Biological Evolution, Cytidine Deaminase, DNA genetics, DNA metabolism, Protein Engineering methods
- Abstract
The immune system is unique among all biological sub-systems in its usage of DNA-editing enzymes to introduce targeted gene mutations and double-strand DNA breaks to diversify antigen receptor genes and combat viral infections. These processes, initiated by specific DNA-editing enzymes, often result in mistargeted induction of genome lesions that initiate and drive cancers. Like other molecules involved in human health and disease, the DNA-editing enzymes of the immune system have been intensively studied in humans and mice, with little attention paid (< 1% of published studies) to the same enzymes in evolutionarily distant species. Here, we present a systematic review of the literature on the characterization of one such DNA-editing enzyme, activation-induced cytidine deaminase (AID), from an evolutionary comparative perspective. The central thesis of this review is that although the evolutionary comparative approach represents a minuscule fraction of published works on this and other DNA-editing enzymes, this approach has made significant impacts across the fields of structural biology, immunology, and cancer research. Using AID as an example, we highlight the value of the evolutionary comparative approach in discoveries already made, and in the context of emerging directions in immunology and protein engineering. We introduce the concept of 5-dimensional (5D) description of protein structures, a more nuanced view of a structure that is made possible by evolutionary comparative studies. In this higher dimensional view of a protein's structure, the classical 3-dimensional (3D) structure is integrated in the context of real-time conformations and evolutionary time shifts (4
th dimension) and the relevance of these dynamics to its biological function (5th dimension)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ghorbani, Quinlan and Larijani.)- Published
- 2021
- Full Text
- View/download PDF
42. Recurrent blisters in a 6-year-old girl.
- Author
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Larijani M, Rubin AI, and Jen M
- Subjects
- Child, Female, Humans, Blister diagnosis, Blister etiology, Skin Abnormalities
- Published
- 2021
- Full Text
- View/download PDF
43. Toxic erythema of chemotherapy affecting the ears of an infant: A case report.
- Author
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Tamazian S, Oboite M, Larijani M, Oliver B, Milbar H, Jen M, and Treat JR
- Subjects
- Child, Humans, Infant, Male, Cytarabine adverse effects, Erythema chemically induced
- Abstract
A 15-month-old boy presented with new onset symmetric erythema of the conchal bowls bilaterally in the setting of treatment with cytarabine. Findings were consistent with a diagnosis of toxic erythema of chemotherapy, an adverse effect of chemotherapy. In this report, we detail this uncommon manifestation in a young child along with a brief literature review of the background, pathophysiology, and treatment strategies of toxic erythema of chemotherapy to increase awareness of this presentation in pediatric populations., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
- Full Text
- View/download PDF
44. Structural plasticity of substrate selection by activation-induced cytidine deaminase as a regulator of its genome-wide mutagenic activity.
- Author
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King JJ and Larijani M
- Subjects
- Catalysis, Catalytic Domain, Computational Chemistry, Cytidine Deaminase chemistry, DNA, Single-Stranded metabolism, Humans, Models, Molecular, Mutagens toxicity, Protein Conformation, RNA metabolism, Substrate Specificity, Cytidine Deaminase metabolism, Genome, Human, Mutagens metabolism
- Abstract
Activation-induced cytidine deaminase (AID) mediates somatic hypermutation and class-switch recombination of antibodies. Computational-biochemical and crystallography analyses of AID have identified three surface grooves for binding single-stranded DNA (ssDNA). Functional studies have also found evidence for RNA-binding motifs on AID. Although AID and the related apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) enzymes share a conserved core, AID uniquely features multiple substrate-binding motifs on its surface. Here we suggest that combinatorial deployment of AID's multiple ssDNA- or RNA-binding motifs yields many substrate-binding modes that can accommodate ssDNA, RNA, or DNA/RNA substrates of diverse structures. We also suggest that AID oligomerization generates yet additional novel substrate-binding modes. We propose that this plasticity in substrate choice is an evolved aspect of AID's structure that contributes to the regulation of its differential mutagenic activity at various loci., (© 2020 Federation of European Biochemical Societies.)
- Published
- 2021
- Full Text
- View/download PDF
45. Activation-induced cytidine deaminase can target multiple topologies of double-stranded DNA in a transcription-independent manner.
- Author
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Branton SA, Ghorbani A, Bolt BN, Fifield H, Berghuis LM, and Larijani M
- Subjects
- Cytidine Deaminase genetics, DNA genetics, DNA metabolism, DNA, Single-Stranded genetics, DNA, Single-Stranded metabolism, Humans, Plasmids chemistry, Plasmids metabolism, Substrate Specificity, Cytidine Deaminase metabolism, DNA chemistry, DNA, Single-Stranded chemistry, Plasmids genetics, Transcription, Genetic
- Abstract
Activation-induced cytidine deaminase (AID) mutates immunoglobulin genes and acts genome-wide. AID targets robustly transcribed genes, and purified AID acts on single-stranded (ss) but not double-stranded (ds) DNA oligonucleotides. Thus, it is believed that transcription is the generator of ssDNA for AID. Previous cell-free studies examining the relationship between transcription and AID targeting have employed a bacterial colony count assay wherein AID reverts an antibiotic resistance stop codon in plasmid substrates, leading to colony formation. Here, we established a novel assay where kb-long dsDNA of varying topologies is incubated with AID, with or without transcription, followed by direct sequencing. This assay allows for an unselected and in-depth comparison of mutation frequency and pattern of AID targeting in the absence of transcription or across a range of transcription dynamics. We found that without transcription, AID targets breathing ssDNA in supercoiled and, to a lesser extent, in relaxed dsDNA. The most optimal transcription only modestly enhanced AID action on supercoiled dsDNA in a manner dependent on RNA polymerase speed. These data suggest that the correlation between transcription and AID targeting may reflect transcription leading to AID-accessible breathing ssDNA patches naturally occurring in de-chromatinized dsDNA, as much as being due to transcription directly generating ssDNA., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
- Published
- 2020
- Full Text
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46. AID, APOBEC3A and APOBEC3B efficiently deaminate deoxycytidines neighboring DNA damage induced by oxidation or alkylation.
- Author
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Diamond CP, Im J, Button EA, Huebert DNG, King JJ, Borzooee F, Abdouni HS, Bacque L, McCarthy E, Fifield H, Berghuis LM, and Larijani M
- Subjects
- Cytidine Deaminase metabolism, Deamination, Deoxycytidine metabolism, Humans, Minor Histocompatibility Antigens metabolism, Oxidation-Reduction, Proteins metabolism, Cytidine Deaminase chemistry, DNA Damage, Deoxycytidine chemistry, Minor Histocompatibility Antigens chemistry, Proteins chemistry
- Abstract
Background: AID/APOBEC3 (A3) enzymes instigate genomic mutations that are involved in immunity and cancer. Although they can deaminate any deoxycytidine (dC) to deoxyuridine (dU), each family member has a signature preference determined by nucleotides surrounding the target dC. This WRC (W = A/T, R = A/G) and YC (Y = T/C) hotspot preference is established for AID and A3A/A3B, respectively. Base alkylation and oxidation are two of the most common types of DNA damage induced environmentally or by chemotherapy. Here we examined the activity of AID, A3A and A3B on dCs neighboring such damaged bases., Methods: Substrates were designed to contain target dCs either in normal WRC/YC hotspots, or in oxidized/alkylated DNA motifs. AID, A3A and A3B were purified and deamination kinetics of each were compared between substrates containing damaged vs. normal motifs., Results: All three enzymes efficiently deaminated dC when common damaged bases were present in the -2 or -1 positions. Strikingly, some damaged motifs supported comparable or higher catalytic efficiencies by AID, A3A and A3B than the WRC/YC motifs which are their most favored normal sequences. Based on the resolved interactions of AID, A3A and A3B with DNA, we modeled interactions with alkylated or oxidized bases. Corroborating the enzyme assay data, the surface regions that recognize normal bases are predicted to also interact robustly with oxidized and alkylated bases., Conclusions: AID, A3A and A3B can efficiently recognize and deaminate dC whose neighbouring nucleotides are damaged., General Significance: Beyond AID/A3s initiating DNA damage, some forms of pre-existing damaged DNA can constitute favored targets of AID/A3s if encountered., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
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47. Pichia pastoris as a host for production and isolation of mutagenic AID/APOBEC enzymes involved in cancer and immunity.
- Author
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Borzooee F and Larijani M
- Subjects
- APOBEC Deaminases isolation & purification, Cytidine Deaminase isolation & purification, Humans, Mutagens, Neoplasms metabolism, APOBEC Deaminases biosynthesis, APOBEC Deaminases genetics, Cytidine Deaminase biosynthesis, Cytidine Deaminase genetics, Immunity, Neoplasms enzymology, Pichia genetics
- Abstract
AID/APOBEC3 enzymes are cytidine deaminases that mutate antibody and retroviral genes and also mediate extensive tumor genome mutagenesis. The study of purified AID/APOBEC3 proteins is challenged by difficulties with their expression and purification arising from genotoxicity in expression hosts, extensive non-specific protein-protein/DNA/RNA interactions and haphazard oligomerization. To date, expression hosts for purification of AID/APOBEC3 enzymes include bacteria, insect and mammalian cells. Here the establishment and optimization of a yeast expression/secretion system for AID/APOBEC3s are reported, followed by comparison with the same enzymes expressed in bacterial and mammalian hosts. AID and APOBEC3G were expressed successfully in Pichia pastoris, each either with an N-terminal GST tag, C-terminal V5-His tag or as untagged native form. It was verified that the yeast-expressed enzymes exhibit identical biochemical properties to those reported using bacterial and mammalian expression, indicating high fidelity of protein folding. It was demonstrated that the system can be adapted for secretion of the enzymes into the media which was used directly in various enzyme assays. The system is also amenable to elimination of bulky fusion tags, providing native untagged enzymes. Thus, P. pastoris is an advantageous expression factory for AID/APOBEC3 enzymes, considering the cost, time, efficiency and quality of the obtained enzymes. The first report is also provided here of a functionally active, untagged, secreted AID, which may become a useful research reagent. A comprehensive comparison is made of the effect of fusion tags and expression hosts on the biochemical actions of AID and APOBEC3G., (Copyright © 2019. Published by Elsevier B.V.)
- Published
- 2019
- Full Text
- View/download PDF
48. Characterization and Transcript Expression Analyses of Atlantic Cod Viperin .
- Author
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Eslamloo K, Ghorbani A, Xue X, Inkpen SM, Larijani M, and Rise ML
- Subjects
- Animals, DNA, Complementary genetics, Exons genetics, Gene Expression Profiling methods, Interferons genetics, Macrophages physiology, Poly I-C genetics, RNA genetics, Signal Transduction genetics, Transcription, Genetic genetics, Fish Proteins genetics, Gadus morhua genetics
- Abstract
Viperin is a key antiviral effector in immune responses of vertebrates including the Atlantic cod ( Gadus morhua ). Using cloning, sequencing and gene expression analyses, we characterized the Atlantic cod viperin at the nucleotide and hypothetical amino acid levels, and its regulating factors were investigated. Atlantic cod viperin cDNA is 1,342 bp long, and its predicted protein contains 347 amino acids. Using in silico analyses, we showed that Atlantic cod viperin is composed of 5 exons, as in other vertebrate orthologs. In addition, the radical SAM domain and C-terminal sequences of the predicted Viperin protein are highly conserved among various species. As expected, Atlantic cod Viperin was most closely related to other teleost orthologs. Using computational modeling, we show that the Atlantic cod Viperin forms similar overall protein architecture compared to mammalian Viperins. qPCR revealed that viperin is a weakly expressed transcript during embryonic development of Atlantic cod. In adults, the highest constitutive expression of viperin transcript was found in blood compared with 18 other tissues. Using isolated macrophages and synthetic dsRNA (pIC) stimulation, we tested various immune inhibitors to determine the possible regulating pathways of Atlantic cod viperin . Atlantic cod viperin showed a comparable pIC induction to other well-known antiviral genes (e.g., interferon gamma and interferon-stimulated gene 15-1 ) in response to various immune inhibitors. The pIC induction of Atlantic cod viperin was significantly inhibited with 2-Aminopurine, Chloroquine, SB202190, and Ruxolitinib. Therefore, endosomal-TLR-mediated pIC recognition and signal transducers (i.e., PKR and p38 MAPK) downstream of the TLR-dependent pathway may activate the gene expression response of Atlantic cod viperin . Also, these results suggest that antiviral responses of Atlantic cod viperin may be transcriptionally regulated through the interferon-activated pathway.
- Published
- 2019
- Full Text
- View/download PDF
49. APOBEC3G Regulation of the Evolutionary Race Between Adaptive Immunity and Viral Immune Escape Is Deeply Imprinted in the HIV Genome.
- Author
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Borzooee F, Joris KD, Grant MD, and Larijani M
- Subjects
- Biological Coevolution genetics, Biological Coevolution immunology, Epitopes, T-Lymphocyte genetics, Epitopes, T-Lymphocyte immunology, Genome, Viral genetics, Genome, Viral immunology, HIV Infections virology, HIV-1 immunology, Histocompatibility Antigens Class I immunology, Histocompatibility Antigens Class I metabolism, Host-Pathogen Interactions immunology, Human Immunodeficiency Virus Proteins genetics, Human Immunodeficiency Virus Proteins immunology, Humans, Mutation, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Cytotoxic metabolism, APOBEC-3G Deaminase metabolism, Adaptive Immunity genetics, HIV Infections immunology, HIV-1 genetics, Host-Pathogen Interactions genetics, Immune Evasion genetics
- Abstract
APOBEC3G (A3G) is a host enzyme that mutates the genomes of retroviruses like HIV. Since A3G is expressed pre-infection, it has classically been considered an agent of innate immunity. We and others previously showed that the impact of A3G-induced mutations on the HIV genome extends to adaptive immunity also, by generating cytotoxic T cell (CTL) escape mutations. Accordingly, HIV genomic sequences encoding CTL epitopes often contain A3G-mutable "hotspot" sequence motifs, presumably to channel A3G action toward CTL escape. Here, we studied the depths and consequences of this apparent viral genome co-evolution with A3G. We identified all potential CTL epitopes in Gag, Pol, Env, and Nef restricted to several HLA class I alleles. We simulated A3G-induced mutations within CTL epitope-encoding sequences, and flanking regions. From the immune recognition perspective, we analyzed how A3G-driven mutations are predicted to impact CTL-epitope generation through modulating proteasomal processing and HLA class I binding. We found that A3G mutations were most often predicted to result in diminishing/abolishing HLA-binding affinity of peptide epitopes. From the viral genome evolution perspective, we evaluated enrichment of A3G hotspots at sequences encoding CTL epitopes and included control sequences in which the HIV genome was randomly shuffled. We found that sequences encoding immunogenic epitopes exhibited a selective enrichment of A3G hotspots, which were strongly biased to translate to non-synonymous amino acid substitutions. When superimposed on the known mutational gradient across the entire length of the HIV genome, we observed a gradient of A3G hotspot enrichment, and an HLA-specific pattern of the potential of A3G hotspots to lead to CTL escape mutations. These data illuminate the depths and extent of the co-evolution of the viral genome to subvert the host mutator A3G.
- Published
- 2019
- Full Text
- View/download PDF
50. Penile basal cell carcinoma in a black kidney transplant recipient.
- Author
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Neidig L, Jin A, Larijani M, and Chung CL
- Published
- 2018
- Full Text
- View/download PDF
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