46 results on '"Mapar M"'
Search Results
2. Metabolic Preference Assay for Rapid Diagnosis of Bloodstream Infections
- Author
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Mapar M, Zhang R, Ryan A. Groves, Pushpker R, Rydzak T, and Ian A. Lewis
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Broad spectrum ,medicine.medical_specialty ,business.industry ,Septic shock ,Mortality rate ,Internal medicine ,Medicine ,Antimicrobial susceptibility ,Antimicrobial ,business ,medicine.disease - Abstract
Bloodstream infections (BSIs) cause >500,000 infections and >80,000 deaths per year in North America. The length of time between the onset of symptoms and administration of appropriate antimicrobials is directly linked to mortality rates. It currently takes 2-5 days to identify BSI pathogens and measure their susceptibility to antimicrobials – a timeline that directly contributes to preventable deaths. To address this, we developed a rapid metabolic preference assay (MPA) that uses the pattern of metabolic fluxes observed in ex-vivo microbial cultures to identify common pathogens and determine their antimicrobial susceptibility profiles. In a head-to-head race with a leading platform (VITEK 2) used in diagnostic laboratories, MPA decreased testing timelines from 40 hours to under 20. If put into practice, this assay could reduce septic shock mortality and reduce the use of broad spectrum antibiotics.One Sentence SummaryMetabolomics enables rapid diagnosis of BSIs.
- Published
- 2021
3. Innovative Surgical System for Breast Cancer Based on Real-time Excising of Hypoxic Lesions Significantly Reduced the Positive Cavity Side Margin
- Author
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Mapar M, Sadeghian N, Naser Namdar, Parisa Aghaee, Hassan Sanati, Mohaghegh P, Mohammad Ali Khayamian, Mahsa Faramarzpour, Zohreh Sadat Miripour, Fereshteh Abbasvandi, Fatemeh Shojaeian, Abdolahad m, Morteza Hassanpour Amiri, Hadi Ghafari, Parisa Hoseinpour, and Mohammad Esmaeil Akbari
- Subjects
medicine.medical_specialty ,Breast cancer ,Text mining ,Margin (machine learning) ,business.industry ,medicine ,Radiology ,medicine.disease ,business - Abstract
Background: For most people, the first step in treatment is to take out the tumor (surgery), so precise and fast diagnosis of any sign of high-risk cells in surgical cavity margins is significant. The frozen pathology method is the conventional standard of intraoperative diagnosis, but the low number of slides prepared from non-fixed tissues prevents us to achieve a perfect diagnosis. Although many improvements in intraoperative margin detection were achieved, still no clinically approved intra-operative technique has been reported for the detection of surgical margins with pathologically approved classification in breast cancer.Methods: From November 2018 to April 2020, 227 patients were registered and 213 with different types of breast tumors (IDC: n=151 (70.9%), ILC: n=6 (2.8%), DCIS: n=38 (17.8%), Atypia: n=8 (3.8%), Benign tumors: n=10 (%4.7)) were randomly assigned for CDP clinical trials. Men made up 2 (1%) of the patients; 211 (99%) were women. Functionalized carbon nanotubes grown on the electrode needles lively and selectively determine the H2O2 released from cancer/atypical cells, through reverse Warburg effect and hypoxia assisted glycolysis pathways, in a quantitative electrochemical manner. The study is registered at Iran National Committee for Ethics in Biomedical Research (IR.TUMS.VCR.REC.1397.355).Result: A real-time electrotechnical system, named cancer diagnostic probe (CDP) (Patent Pub. No.: US 2018/0299401A1), has been developed and clinically approved for breast cancer surgery (National Certificate ID:14006918495) to find the presence of pre-neoplastic/neoplastic cells in-vivo. Here, Functionalized carbon nanotubes grown on the electrode needles lively and selectively determine the H2O2 released from cancer or atypical cells, through reverse Warburg effect and hypoxia assisted glycolysis pathways, in quantitative electrochemical manner. A matched clinical diagnostic categorization between the pathological results and response peaks of CDP was proposed based on pathological classifications of WHO. Conclusion: The clinical ability of CDP was verified on more than 1300 human in-vivo breast samples with sensitivity and specificity of 93%, and 97%, respectively. After passing many trials and standard examinations, the system received production and clinical use certifications as a surgeon assistant system for usage in the operating room.
- Published
- 2020
4. How to integrate Sustainability Teaching and Learning in Higher Education Institutions?
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Moreno Pires, S., Nicolau, M., Ferreira Dias, M., Horta, D., Mapar, M., Bacelar Nicolau, P., Caeiro, S., Patrizi, N., Pulselli, F. M., Galli, A., and Malandrakis, G.
- Published
- 2020
- Full Text
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5. State-of-the-art review on selective laser melting of ceramics
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Yeong, W, primary, Yap, C, additional, Mapar, M, additional, and Chua, C, additional
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- 2013
- Full Text
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6. Preparation and flowability characterization of ceramic powders for Selective Laser Melting
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Mapar, M, primary, Zhang, D, additional, Liu, Z, additional, Yeong, W, additional, Chua, C, additional, Tay, B, additional, Geramifard, O, additional, Maleksaeedi, S, additional, and Wiria, F, additional
- Published
- 2013
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7. Efficacy of sulfasalazine in the treatment of generalized lichen planus: randomized double-blinded clinical trial on 52 patients
- Author
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Omidian, M, Ayoobi, A, Mapar, M A, Feily, A, and Cheraghian, B
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- 2010
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8. Chronic zosteriform cutaneous leishmaniasis
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Omidian, M. and Mapar, M.
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Leishmaniasis, Cutaneous -- Causes of ,Leishmaniasis, Cutaneous -- Case studies - Abstract
Byline: M. Omidian, M. Mapar Cutaneous leishmanasis (CL) may present with unusual clinical variants such as acute paronychial, annular, palmoplantar, zosteriform, erysipeloid, and sporotrichoid. The zosteriform variant has rarely been [...]
- Published
- 2006
9. The Effect of Over-Expression of miR-20a on Cell Proliferation of Human T Cell Leukemia Cell Line.
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M., Razavi Hashemi, Vahabpour R., Ranji N., Sanati M. H., Mapar M., and Sadat S. M.
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ADULT T-cell leukemia ,LEUKEMIA ,CANCER chemotherapy ,MICRORNA ,GENETIC regulation - Abstract
Background: Acute T Cell Leukemia (ALL) is an aggressive and prevalent human malignancy. Chemotherapy is the most frequent therapeutic strategy; however, cytotoxicity and recurrence of cancer are the main concerns. The discovery of microRNA (miRNA) drew the attention of scientists who were working on targeted cancer therapy to use the potential of gene regulation by using this small RNAs. Methods: miRanda, TargetScan, miRDB databases, and miRWalk software were applied to find probable mi- RNAs targeting 3'UTR of JAK1, STAT3, SOCS6, AKT1, APAF, BID, and Caspase9 mRNA. A lentiviral vector encoding miR-20a was used for overexpression of the miR-20a in C8166 cell lines to investigate the expression level of genes that are associated with the JAK/STAT signaling pathway and apoptosis using quantitative RTPCR. The effects of miR-20a overexpression also were examined on cell-cycle progression by flow cytometry. Results: qRT-PCR results indicated that overexpression of miR-20a in C8166 cells resulted in significantly elevated expression of BID and Caspase9 (p-value < 0.01). Overexpression of miR-20a in C8166 cells led to cell cycle arrest at the G0/G1 phase. Conclusions: The results suggested miR-20a may act as a tumor suppressor in CD4+ T cells and also has a potential therapeutic in these kinds of cancers. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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10. Selective Laser Melting of aluminium alloy using a uniform beam profile
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Loh, L.E., primary, Liu, Z.H., additional, Zhang, D.Q., additional, Mapar, M., additional, Sing, S.L., additional, Chua, C.K., additional, and Yeong, W.Y., additional
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- 2014
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11. A Numerical Study on the Melt Track in Selective Laser Melting Using Aluminium Alloy 6061
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Loh, L. E., primary, Chua, C. K., additional, Liu, Z. H., additional, Zhang, D. Q., additional, Sing, S. L., additional, and Mapar, M., additional
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- 2014
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12. The optimum value of alpha in the pre-specified coverage control algorithm in wireless sensor networks to achieve minimum active nodes.
- Author
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Mapar, M., Sotoudeh, A.H., and Negahdar, M.
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- 2008
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13. Adaptive Method for Decreasing Over-covered Areas in Wireless Sensor Networks.
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Negahdar, M., Ardebilipour, M., and Mapar, M.
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- 2008
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14. A method for coverage control in wireless sensor networks with two degrees of freedom.
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Negahdar, M., Ardebilipour, M., and Mapar, M.
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- 2008
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15. A New Method for Contractors HSE Ranking at the Pre-Contract Stage Based on Contract Level.
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Jafari, M. J., Mapar, M., and Mansouri, N.
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- 2013
16. A New Method for Contractors HSE Ranking at the Pre-Contract Stage Based on Contract Level
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Jafari, M. J., Mapar, M., and Nabiollah Mansouri
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hse ,assessment ,lcsh:R ,lcsh:Medicine ,contractor ,management - Abstract
Background and aims: Evaluation of the contractor’s HSE is a key issue for the employer that influences the selection of a contractor. An appropriate method of assessment can play a significant role in the selection of qualified contractors. This paper presents a new method for ranking of contractor’s HSE at pre-contract stage of a project. Methods: To develop this new evaluation method, the c ontracts were categorized in 3 groups of advanced, medium and preliminary. In order to pre-assess the contractors’ status prior to their participation in bids, an HSE data questionnaire was developed in the frame of 40 questions. Then 29 indices were developed for primary HSE assessment based on International Association of Oil and Gas Producers (OGP). Because the role of each index is different in each category of contracts thus, seven elements of HSE model were weighted on the basis of contract category. Contractors scoring system was developed in each category of contract based on the obtained weights. Finally the contractors were categorized in four groups of A, B, C and D based on their scores obtained from their HSE evaluation. Results: The results revealed that each term of HSE have different weight in each contract category. In advanced (group 1) and medium (group 2) contracts, the leadership plus commitment (coefficient of 4.9 and 4.3 respectively) and in preliminary contracts the execution and monitoring (coefficient 3.3) have the highest weights. The Strategy and goals have the minimum weight in all 3 types of contracts (e.g. 4.4 in advanced, 3.6 in medium and 2.4 in preliminary contracts). The minimum score required for an A group contractor to get an advanced contract is 537 while the maximum score of a D group contractor to obtain a preliminary contract is 123. Conclusion: The new developed method is able to rank the HSE of contractors prior to sign the contract.
17. Lack of TNF-α gene polymorphism (rs1799724) association with sustained virological response in Iranian patients with chronic HCV infection
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Larijani, M. S., Bahiraei, N., Nikbin, M., Nasir Mohajel, Rad, L. N., Baghbani, F., Mapar, M., and Sadat, S. M.
18. Estimating the safety economic value in Esfahan Oil Refinery with contingent valuation method
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Maheronnaghsh, S., Mostafa Panahi, Mohammadfam, I., and Mapar, M.
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willing to accept ,economic valuation of safety ,lcsh:R ,refinery ,lcsh:Medicine - Abstract
Background and aims: Planning to increase production and tends to increase the efficiency of human resources in productive organizations without estimating the economic costs imposed on the organization, cause the actual value of safety is ignored in workplaces. Among the financial cost of the productive organizations, the subject of safety promotion through decreasing the probable hazards will cause to impose the amount of extra costs to employers that are often faced them with the reluctance and therefore they will try to decrease these mentioned costs. The object of this study is to determine the numerical value of safety from the perspective of the refinery staff through computing the amount of money which the staff tend to receive to tolerate unsafe conditions in the workplace. This amount will be equivalent to the importance of preventing accidents and promoting the safety condition in the workplace from the perspective of the labor force. Methods: In this study, by applying Contingent Valuation Method (CVM) and determining the amount of willingness to accept (WTA) of employees in exchange for the waiver of improving safety in the workplace, the economic value of safety in Esfahan Oil Refining Company was estimated from the employeechr('39')s perspective. For this purpose, a questionnaire was provided and by creating a hypothetical market scenario for safety as a non-traded goods, data relating to the safety value were asked from the number of 140 operational employees and analyzed by applying 2-steps questionnaire including the pre-test and final test during 2014. Results: Based on the results of this study, the mean of willingness to accept (WTA) a month for each employee at the refinery was estimated at 2 million and five hundred thousand rials. The total economic value estimated for the safety of the refinery personnel for 1,300 people employed in operational units, estimated 39 billion rails. Considering the total annual cost of refinery safety that is 6,700,000,000 rials, it was clear from the employeechr('39')s perspective, the economic value of safety is 5.8 times greater than the cost of refinery existing safety programs conditions in the workplace. Conclusion: According to this point of view, the need to review the annual budget required to implement safety measures described and from an economic point focusing on the search for optimal conditions for market efficiency and cost effectiveness of the safety measures is important.
19. Comparison of the efficacy and safety of zinc sulfate vs. Placebo in the treatment of pruritus of hemodialytic patients: A pilot randomized, triple-blind study
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Mapar, M. A., Pazyar, N., Siahpoosh, A., Seyed Mahmoud Latifi, Beladi Mousavi, S. S., and Khazanee, A.
20. Comparative study of 5% potassium hydroxide solution vs. 0.1% tretinoin lotion in the treatment of plane warts: A randomized controlled trial
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Yaghoobi, R., Tajalli, M., Mapar, M. A., and nader pazyar
21. Diverse molecular mechanisms underpinning Staphylococcus aureus small colony variants.
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Mapar M, Rydzak T, Hommes JW, Surewaard BGJ, and Lewis IA
- Abstract
Small colony variants (SCVs) of Staphylococcus aureus are a relatively rare but clinically significant growth morphotype. Infections with SCVs are frequently difficult to treat, inherently antibiotic-resistant, and can lead to persistent infections. Despite a long history of research, the molecular underpinnings of this morphotype and their impact on the clinical trajectory of infections remain unclear. However, a growing body of literature indicates that SCVs are caused by a diverse range of molecular factors. These recent findings suggest that SCVs should be thought of as an ensemble collection of loosely related phenotypes, and not as a single phenomenon. This review describes the diverse mechanisms currently known to contribute to SCVs and proposes an ensemble model for conceptualizing this morphotype., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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22. Comparative study of stability and activity of wild-type and mutant human carbonic anhydrase II enzymes using molecular dynamics and docking simulations.
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Mapar M, Taghdir M, and Ranjbar B
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- Humans, Mutation, Carbon Dioxide metabolism, Carbon Dioxide chemistry, Nitrophenols metabolism, Nitrophenols chemistry, Ligands, Carbonic Anhydrase Inhibitors pharmacology, Carbonic Anhydrase Inhibitors chemistry, Protein Conformation, Carrier Proteins, Nerve Tissue Proteins, Carbonic Anhydrase II chemistry, Carbonic Anhydrase II genetics, Carbonic Anhydrase II metabolism, Molecular Dynamics Simulation, Enzyme Stability, Acetazolamide pharmacology, Molecular Docking Simulation
- Abstract
The human carbonic anhydrase II (HCA II) enzyme is a cytosolic protein located in the membrane of red blood cells that reversible hydration of carbon dioxide (CO
2 ). Considering the critical role of the HCA II and the effects of some mutations on the activity and stability of the enzyme in humans, several computational methods are used to study the structure and dynamics of the wild-type and the mutant enzymes with three ligands, CO2 , 4-nitrophenyl acetate and acetazolamide. Our results of MD simulation of a wild-type enzyme with 4-nitrophenyl acetate show that it created essential effects on the fluctuation of this enzyme and made it more unstable and less compact than the same enzyme without ligand. In the MD of the mutant enzyme with 4-nitrophenyl acetate ligand, no significant difference is observed between with and without ligand. The affinity of the wild-type enzyme to the 4-nitrophenyl acetate is notably higher than the mutant enzyme with the same ligand. Furthermore, results showed that wild-type and mutant enzymes with CO2 are more favorable in stability and flexibility than the same enzymes without ligand. The MD results of wild-type with acetazolamide indicate instability compare without ligand, but in MD of mutant enzyme with acetazolamide show that it more stable and compact than the same enzyme without ligand. Finally, Comparing protein trajectories to assess the impact of ligands on the stability and activity of HCA II enzymes can have medical applications and can in the engineering and design of new variants of carbonic anhydrase enzyme., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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23. Achieving efficient clonal beta cells transfection using nanostraw/nanopore-assisted electroporation.
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Ekstrand F, Mapar M, Ruhrmann S, Bacos K, Ling C, and Prinz CN
- Abstract
The prospect of being able to efficiently inject large plasmids in insulin-producing beta cells is very attractive for diabetes research. However, conventional transfection methods suffer from high cytotoxicity or low transfection efficiency, which negatively affect their outcome. In contrast, nanostraw electroporation is a gentle method that can provide a high transfection efficiency while maintaining high cell viability. While nanostraw electroporation has gone through some method optimization in the past, such as tuning the pulse frequency, amplitude, and duration, the effect of other parameters has not been thoroughly investigated. Here, we demonstrate efficient transfection of clonal beta cells and investigate the effect of voltage at a fixed inter-electrode distance, cell density, and cargo solution conductivity on transfection efficiency. We used GFP-encoding DNA plasmids stained with an intercalating dye to enable immediate analysis and assessment of the electrophoretic transport of cargo. Moreover, we ran simulations to assess how cargo buffer conductivity impacts the transfection efficiency by affecting the voltage drop on the nanostraws and cell membrane during electroporation. Both experiments and simulations show that MilliQ water as the cargo buffer yields the best transfection efficiency. We also show that the cell density should be adjusted to maximize the number of cells interfacing the nanostraws and avoid cell stacking. Finally, we compared the transfection efficiency when using nanostraws and nanopores. Whereas the amount of GFP plasmids injected using nanostraws is larger than for nanopores, the outcome in terms of GFP fluorescence 48 h after transfection was worse than for nanopores. Moreover, when using nanostraws, fewer cells were found on the substrate 48 h after transfection compared to when using nanopores. This suggests that injecting substantial amounts of plasmids in cells can affect their proliferation and/or viability, and that nanopore electroporation, as a simpler method, is an interesting alternative to nanostraws in achieving efficient and gentle clonal beta cell transfection., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
- Published
- 2024
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24. Effects of Two Remineralizing Agents in Combination with Er:YAG and CO 2 Laser Irradiation on Microhardness of Demineralized Enamel: A Preliminary In Vitro Study.
- Author
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Mapar M, Gholizadeh S, and Moalemnia M
- Abstract
Objectives: This study assessed the effects of two remineralizing agents namely MI Paste Plus containing casein phosphopeptide amorphous calcium phosphate fluoride (CPP-ACFP) and Remin Pro containing hydroxyapatite, fluoride and xylitol (HFX) with/without erbium-doped yttrium aluminium garnet (Er:YAG) and CO
2 laser irradiation on demineralized enamel microhardness. Materials and Methods: In this in vitro study, 70 sound human premolars were mesiodistally sectioned, demineralized at a pH of 4.6 for 8 hours, and randomly divided into 7 remineralization groups (n=10): of (I) MI Paste Plus (CPP-ACFP), (II) Remin Pro (HFX), (III) MI Paste Plus+CO2 laser (0.7 W power, 50 Hz), (IV) Remin Pro+CO2 laser, (V) MI Paste Plus+Er:YAG laser (1 W power, 10 Hz), (VI) Remin Pro+Er:YAG laser, and (VII) negative control. The Vickers hardness number of specimens was then measured. The groups were compared by one-way ANOVA and Tukey's test (α=0.05). Results: The mean microhardness was 319.8±49.9, 325.3±44.6, 359.4±35.7, 296.4±33.7, 319.9±58.1, 358.9±28.4, and 240.0±41.6 kg/mm2 in groups 1 to 7, respectively. The difference in microhardness was significant among the groups (P<0.0001). Pairwise comparisons revealed significant differences in microhardness between all groups (P≤0.03) except between groups 1 and 2, 1 and 5, 2 and 5, and 3 and 6 (P>0.05). Conclusion: Both Remin Pro (containing HFX) and MI Paste Plus (containing CPP-ACFP) can cause enamel remineralization. MI Paste Plus+CO2 laser irradiation and Remin Pro+Er:YAG laser irradiation were significantly more effective than the application of each remineralizing agent alone ., Competing Interests: None declared., (Copyright © 2024 The Authors. Published by Tehran University of Medical Sciences.)- Published
- 2024
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25. Label-free quantification of protein binding to lipid vesicles using transparent waveguide evanescent-field scattering microscopy with liquid control.
- Author
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Mapar M, Sjöberg M, Zhdanov VP, Agnarsson B, and Höök F
- Abstract
Recent innovations in microscopy techniques are paving the way for label-free studies of single nanoscopic biological entities such as viruses, lipid-nanoparticle drug carriers, and even proteins. One such technique is waveguide evanescent-field microscopy, which offers a relatively simple, yet sensitive, way of achieving label-free light scattering-based imaging of nanoparticles on surfaces. Herein, we extend the application of this technique by incorporating microfluidic liquid control and adapting the design for use with inverted microscopes by fabricating a waveguide on a transparent substrate. We furthermore formulate analytical models describing scattering and fluorescence intensities from single spherical and shell-like objects interacting with evanescent fields. The models are then applied to analyze scattering and fluorescence intensities from adsorbed polystyrene beads and to temporally resolve cholera-toxin B (CTB) binding to individual surface-immobilized glycosphingolipid G
M1 containing vesicles. We also propose a self-consistent means to quantify the thickness of the CTB layer, revealing that protein-binding to individual vesicles can be characterized with sub-nm precision in a time-resolved manner., Competing Interests: Fredrik Höök, Björn Agnarsson and Mattias Sjöberg are co-founders of the company Nanolyze AB, which commercializes waveguide-based microscopy systems. All other authors declare no competing interests., (Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)- Published
- 2023
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26. Microleakage Evaluation of Two Methacrylate-Based Composites (GC Kalore and Luna SDI) in Class II Restorations: A Laboratory Study.
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Moradi K, Mahmoudinezhad SS, and Mapar M
- Abstract
Objective: In recent years, dental composite resins such as tooth-colored restoration are frequently used to restore dental cavities, coronal fractures, and congenital defects. This study aimed to evaluate the microleakage of two methacrylate-based composites (GC Kalore and Luna SDI) in class II restorations., Materials and Methods: In this experimental study, a total of 18 intact human premolars previously extracted for periodontal and orthodontic reasons were randomly divided into two groups. Similar class II cavities (box only) were prepared on all teeth and restored with two different composites. In group 1, a bonding agent (Single Bond 2-SB2; 3M ESPE) and Luna SDI composite in mesial cavities and GC Kalore composite in distal cavities were used. In group 2, Single Bond 2 and GC Kalore composite in mesial cavities and Luna SDI composite in distal cavities were applied. They were then subjected to 2000 thermal cycles in a water bath between 5-55°C (dwell time: 30 seconds in every bath and transfer time: 10 seconds). Then, they were immersed in a 2% basic fuchsin dye solution for 24 hours. After rinsing with water, they were sectioned mesiodistally and evaluated for microleakage using a stereomicroscope., Results: Independent t -test (Mann-Whitney test) showed no statistically significant difference for microleakage in mesial and distal class II restorations between GC Kalore composite and Luna SDI composite ( p = 1.000) ( p = 0.852). A total of 83.4% of the Luna SDI composite samples and 66.6% of the GC Kalore composite had a microleakage score of ≤3 in class II cavities., Conclusion: In the present study, marginal microleakage was found mainly at the gingival floor extending to 1/3 of the axial wall for the Luna SDI composite and GC Kalore composite. Furthermore, no statistically significant difference was found between the microleakage of the Class II cavities restored with Luna SDI composite and GC Kalore composite., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Kooshan Moradi et al.)
- Published
- 2022
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27. Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion.
- Author
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Aliakbarinodehi N, Gallud A, Mapar M, Wesén E, Heydari S, Jing Y, Emilsson G, Liu K, Sabirsh A, Zhdanov VP, Lindfors L, Esbjörner EK, and Höök F
- Subjects
- Lipids chemistry, Kinetics, RNA, Messenger genetics, Lipoproteins, Hydrogen-Ion Concentration, RNA, Small Interfering genetics, Protein Corona, Nanoparticles chemistry
- Abstract
Lipid nanoparticles (LNPs) have emerged as potent carriers for mRNA delivery, but several challenges remain before this approach can offer broad clinical translation of mRNA therapeutics. To improve their efficacy, a better understanding is required regarding how LNPs are trapped and processed at the anionic endosomal membrane prior to mRNA release. We used surface-sensitive fluorescence microscopy with single LNP resolution to investigate the pH dependency of the binding kinetics of ionizable lipid-containing LNPs to a supported endosomal model membrane. A sharp increase of LNP binding was observed when the pH was lowered from 6 to 5, accompanied by stepwise large-scale LNP disintegration. For LNPs preincubated in serum, protein corona formation shifted the onset of LNP binding and subsequent disintegration to lower pH, an effect that was less pronounced for lipoprotein-depleted serum. The LNP binding to the endosomal membrane mimic was observed to eventually become severely limited by suppression of the driving force for the formation of multivalent bonds during LNP attachment or, more specifically, by charge neutralization of anionic lipids in the model membrane due to their association with cationic lipids from earlier attached LNPs upon their disintegration. Cell uptake experiments demonstrated marginal differences in LNP uptake in untreated and lipoprotein-depleted serum, whereas lipoprotein-depleted serum increased mRNA-controlled protein (eGFP) production substantially. This complies with model membrane data and suggests that protein corona formation on the surface of the LNPs influences the nature of the interaction between LNPs and endosomal membranes.
- Published
- 2022
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28. Biomarker enrichment medium: A defined medium for metabolomic analysis of microbial pathogens.
- Author
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Mapar M, Rydzak T, Groves RA, and Lewis IA
- Abstract
Microbes have diverse metabolic capabilities and differences in these phenotypes are critical for differentiating strains, species, and broader taxa of microorganisms. Recent advances in liquid chromatography-mass spectrometry (LC-MS) allow researchers to track the complex combinations of molecules that are taken up by each cell type and to quantify the rates that individual metabolites enter or exit the cells. This metabolomics-based approach allows complex metabolic phenotypes to be captured in a single assay, enables computational models of microbial metabolism to be constructed, and can serve as a diagnostic approach for clinical microbiology. Unfortunately, metabolic phenotypes are directly affected by the molecular composition of the culture medium and many traditional media are subject to molecular-level heterogeneity. Herein, we show that commercially sourced Mueller Hinton (MH) medium, a Clinical and Laboratory Standards Institute (CLSI) approved medium for clinical microbiology, has significant lot-to-lot and supplier-to-supplier variability in the concentrations of individual nutrients. We show that this variability does not affect microbial growth rates but does affect the metabolic phenotypes observed in vitro -including metabolic phenotypes that distinguish six common pathogens. To address this, we used a combination of isotope-labeling, substrate exclusion, and nutritional supplementation experiments using Roswell Park Memorial Institute (RPMI) medium to identify the specific nutrients used by the microbes to produce diagnostic biomarkers, and to formulate a Biomarker Enrichment Medium (BEM) as an alternative to complex undefined media for metabolomics research, clinical diagnostics, antibiotic susceptibility testing, and other applications where the analysis of stable microbial metabolic phenotypes is important., (Copyright © 2022 Mapar, Rydzak, Groves and Lewis.)
- Published
- 2022
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29. Methods for Quantifying the Metabolic Boundary Fluxes of Cell Cultures in Large Cohorts by High-Resolution Hydrophilic Liquid Chromatography Mass Spectrometry.
- Author
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Groves RA, Mapar M, Aburashed R, Ponce LF, Bishop SL, Rydzak T, Drikic M, Bihan DG, Benediktsson H, Clement F, Gregson DB, and Lewis IA
- Subjects
- Chromatography, Liquid methods, Humans, Hydrophobic and Hydrophilic Interactions, Mass Spectrometry methods, Cell Culture Techniques, Metabolomics methods
- Abstract
Metabolomics is a mainstream approach for investigating the metabolic underpinnings of complex biological phenomena and is increasingly being applied to large-scale studies involving hundreds or thousands of samples. Although metabolomics methods are robust in smaller-scale studies, they can be challenging to apply to larger cohorts due to the inherent variability of liquid chromatography mass spectrometry (LC-MS). Much of this difficulty results from the time-dependent changes in the LC-MS system, which affects both the qualitative and quantitative performances of the instrument. Herein, we introduce an analytical strategy for addressing this problem in large-scale microbial studies. Our approach quantifies microbial boundary fluxes using two zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) columns that are plumbed to enable offline column equilibration. Using this strategy, we show that over 397 common metabolites can be resolved in 4.5 min per sample and that metabolites can be quantified with a median coefficient of variation of 0.127 across 1100 technical replicates. We illustrate the utility of this strategy via an analysis of 960 strains of Staphylococcus aureus isolated from bloodstream infections. These data capture the diversity of metabolic phenotypes observed in clinical isolates and provide an example of how large-scale investigations can leverage our novel analytical strategy.
- Published
- 2022
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30. Metabolic preference assay for rapid diagnosis of bloodstream infections.
- Author
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Rydzak T, Groves RA, Zhang R, Aburashed R, Pushpker R, Mapar M, and Lewis IA
- Subjects
- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Biological Assay, Humans, Anti-Infective Agents, Sepsis diagnosis, Shock, Septic
- Abstract
Bloodstream infections (BSIs) cause >500,000 infections and >80,000 deaths per year in North America. The length of time between the onset of symptoms and administration of appropriate antimicrobials is directly linked to mortality rates. It currently takes 2-5 days to identify BSI pathogens and measure their susceptibility to antimicrobials - a timeline that directly contributes to preventable deaths. To address this, we demonstrate a rapid metabolic preference assay (MPA) that uses the pattern of metabolic fluxes observed in ex-vivo microbial cultures to identify common pathogens and determine their antimicrobial susceptibility profiles. In a head-to-head race with a leading platform (VITEK 2, BioMérieux) used in diagnostic laboratories, MPA decreases testing timelines from 40 hours to under 20. If put into practice, this assay could reduce septic shock mortality and reduce the use of broad spectrum antibiotics., (© 2022. The Author(s).)
- Published
- 2022
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31. Human study on cancer diagnostic probe (CDP) for real-time excising of breast positive cavity side margins based on tracing hypoxia glycolysis; checking diagnostic accuracy in non-neoadjuvant cases.
- Author
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Miripour ZS, Abbasvandi F, Aghaee P, Shojaeian F, Faramarzpour M, Mohaghegh P, Hoseinpour P, Namdar N, Hassanpour Amiri M, Ghafari H, Parniani M, Kaviani A, Alamdar S, NajafiKhoshnoo S, Sanati H, Mapar M, Sadeghian N, Akbari ME, Yunesian M, and Abdolahad M
- Subjects
- Female, Humans, Glycolysis, Hypoxia, Prospective Studies, Reproducibility of Results, Sensitivity and Specificity, Breast Neoplasms diagnosis, Breast Neoplasms pathology, Breast Neoplasms surgery, Margins of Excision
- Abstract
Background: Cancer diagnostic probe (CDP) had been developed to detect involved breast cavity side margins in real-time (Miripour et al. Bioeng Transl Med. e10236.). Here, we presented the results of the in vivo human model CDP studies on non-neoadjuvant cases., Methods: This study is a prospective, blind comparison to a gold standard, and the medical group recruited patients. CDP and frozen data were achieved before the permanent pathology experiment. The main outcome of the study is surgical margin status. From November 2018 to April 2020, 202 patients were registered, and 188 were assigned for the study. Breast-conserving surgery at any age or gender, re-surgery due to re-currency, or involved margins are acceptable. Patients must be non-neoadjuvant. The reliability of CDP scoring had been evaluated by the pathology of the scored IMs. Then, three models of the study were designed to compare CDP with the frozen sections. Receiver operating characteristic (ROC) curves and AUC were measured based on the permanent postoperative pathology gold standard., Results: A matched clinical diagnostic categorization between the pathological results of the tested IMs and response peaks of CDP on 113 cases, was reported (sensitivity = 97%, specificity = 89.3%, accuracy = 92%, positive predictive value (PPV) = 84.2%, and negative predictive value (NPV) = 98%). Study A showed the independent ability of CDP for IM scoring (sensitivity = 80%, specificity = 90%, accuracy = 90%, PPV = 22.2%, and NPV = 99.2%). Study B showed the complementary role of CDP to cover the missed lesions of frozen sections (sensitivity = 93.8%, specificity = 91%, accuracy = 91%, PPV = 55.6%, and NPV = 99.2%). Study C showed the ability of CDP in helping the pathologist to reduce his/her frozen miss judgment (specificity = 92%, accuracy = 93%, PPV = 42.1%, and NPV = 100%). Results were reported based on the post-surgical permanent pathology gold standard., Conclusion: CDP scoring ability in intra-operative margin detection was verified on non-neoadjuvant breast cancer patients. Non-invasive real-time diagnosis of IMs with pathological values may make CDP a distinct tool with handheld equipment to increase the prognosis of breast cancer patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2022
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32. Genetic and Molecular Analysis of Root Hair Development in Arabis alpina .
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Mapar M, Chopra D, Stephan L, Schrader A, Sun H, Schneeberger K, Albani M, Coupland G, and Hülskamp M
- Abstract
Root hair formation in Arabidopsis thaliana is a well-established model system for epidermal patterning and morphogenesis in plants. Over the last decades, many underlying regulatory genes and well-established networks have been identified by thorough genetic and molecular analysis. In this study, we used a forward genetic approach to identify genes involved in root hair development in Arabis alpina , a related crucifer species that diverged from A. thaliana approximately 26-40 million years ago. We found all root hair mutant classes known in A. thaliana and identified orthologous regulatory genes by whole-genome or candidate gene sequencing. Our findings indicate that the gene-phenotype relationships regulating root hair development are largely conserved between A. thaliana and A. alpina . Concordantly, a detailed analysis of one mutant with multiple hairs originating from one cell suggested that a mutation in the SUPERCENTIPEDE1 ( SCN1 ) gene is causal for the phenotype and that AaSCN1 is fully functional in A. thaliana . Interestingly, we also found differences in the regulation of root hair differentiation and morphogenesis between the species, and a subset of root hair mutants could not be explained by mutations in orthologs of known genes from A. thaliana . This analysis provides insight into the conservation and divergence of root hair regulation in the Brassicaceae., 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 Mapar, Chopra, Stephan, Schrader, Sun, Schneeberger, Albani, Coupland and Hülskamp.)
- Published
- 2021
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33. Electrochemical tracing of hypoxia glycolysis by carbon nanotube sensors, a new hallmark for intraoperative detection of suspicious margins to breast neoplasia.
- Author
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Miripour ZS, Abbasvandi F, Aghaee P, NajafiKhoshnoo S, Faramarzpour M, Mohaghegh P, Hoseinpour P, Namdar N, Amiri MH, Ghafari H, Zareie S, Shojaeian F, Sanati H, Mapar M, Sadeghian N, Akbari ME, Khayamian MA, and Abdolahad M
- Abstract
For most people, the first step in treatment is to take out the tumor (surgery), so precise and fast diagnosis of any sign of high-risk and neoplastic cells, especially in surgical cavity margins, is significant. The frozen pathology method is the conventional standard of intraoperative diagnosis, but the low number of slides prepared from non-fixed tissues prevents us from achieving a perfect diagnosis. Although many improvements in intraoperative margin detection were achieved, still real-time detection of neoplastic lesions is crucial to improving diagnostic quality. Functionalized carbon nanotubes grown on the electrode needles lively and selectively determine the H
2 O2 released from cancer/atypical cells through reverse Warburg effect and hypoxia assisted glycolysis pathways in a quantitative electrochemical manner. The study was carried out on cell lines, 57 in vivo mice models with breast cancer, and 258 fresh in vitro samples of breast cancer tumors. A real-time electrotechnical system, named cancer diagnostic probe (CDP) (US Patent Pub. No.: US 2018/02991 A1, US 2021/0007638 A1, and US 2021/0022650 A1 [publications], and US 10,786,188 B1 [granted]), has been developed to find pre-neoplastic/neoplastic cells in vivo in a quantitative electrochemical manner by tracing hypoxia glycolysis byproducts. Matched pathological evaluations with response peaks of CDP were found based on the presence of neoplasia (from atypia to invasive carcinoma) in live breast tissues. The ability of CDP to find neoplastic lesions in mice models in vivo and fresh breast tumors in vitro was verified with sensitivity and specificity of 95% and 97%, respectively. The system may help a surgeon assistant system for usage in the operating room after passing many trials and standard examinations in the future., Competing Interests: Four USA patents (one granted; US Patent US10,786,188 B1, and three publications; US Patent App. US2018/0299401 A1, US2021/0007638 A1, and US2021/0022650 A1) have been published based on this work. M.A. is a member of the scientific advisory board of Arya Nano biosensor Manufacturer Co., a company that is commercializing CDP technology. The remaining authors declare that they have no competing interests., (© 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)- Published
- 2021
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34. Time-Resolved and Label-Free Evanescent Light-Scattering Microscopy for Mass Quantification of Protein Binding to Single Lipid Vesicles.
- Author
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Sjöberg M, Mapar M, Armanious A, Zhdanov VP, Agnarsson B, and Höök F
- Subjects
- Light, Lipids, Protein Binding, Surface Plasmon Resonance, Microscopy, Nanoparticles
- Abstract
In-depth understanding of the intricate interactions between biomolecules and nanoparticles is hampered by a lack of analytical methods providing quantitative information about binding kinetics. Herein, we demonstrate how label-free evanescent light-scattering microscopy can be used to temporally resolve specific protein binding to individual surface-bound (∼100 nm) lipid vesicles. A theoretical model is proposed that translates protein-induced changes in light-scattering intensity into bound mass. Since the analysis is centered on individual lipid vesicles, the signal from nonspecific protein binding to the surrounding surface is completely avoided, offering a key advantage over conventional surface-based techniques. Further, by averaging the intensities from less than 2000 lipid vesicles, the sensitivity is shown to increase by orders of magnitude. Taken together, these features provide a new avenue in studies of protein-nanoparticle interaction, in general, and specifically in the context of nanoparticles in medical diagnostics and drug delivery.
- Published
- 2021
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35. Independent Size and Fluorescence Emission Determination of Individual Biological Nanoparticles Reveals that Lipophilic Dye Incorporation Does Not Scale with Particle Size.
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Jõemetsa S, Joyce P, Lubart Q, Mapar M, Celauro E, Agnarsson B, Block S, Bally M, Esbjörner EK, Jeffries GDM, and Höök F
- Abstract
Advancements in nanoparticle characterization techniques are critical for improving the understanding of how biological nanoparticles (BNPs) contribute to different cellular processes, such as cellular communication, viral infection, as well as various drug-delivery applications. Since BNPs are intrinsically heterogeneous, there is a need for characterization methods that are capable of providing information about multiple parameters simultaneously, preferably at the single-nanoparticle level. In this work, fluorescence microscopy was combined with surface-based two-dimensional flow nanometry, allowing for simultaneous and independent determination of size and fluorescence emission of individual BNPs. In this way, the dependence of the fluorescence emission of the commonly used self-inserting lipophilic dye 3,3'-dioctadecyl-5,5'-di(4-sulfophenyl)oxacarbocyanine (SP-DiO) could successfully be correlated with nanoparticle size for different types of BNPs, including synthetic lipid vesicles, lipid vesicles derived from cellular membrane extracts, and extracellular vesicles derived from human SH-SY5Y cell cultures; all vesicles had a radius, r , of ∼50 nm and similar size distributions. The results demonstrate that the dependence of fluorescence emission of SP-DiO on nanoparticle size varies significantly between the different types of BNPs, with the expected dependence on membrane area, r
2 , being observed for synthetic lipid vesicles, while a significant weaker dependence on size was observed for BNPs with more complex composition. The latter observation is attributed to a size-dependent difference in membrane composition, which may influence either the optical properties of the dye and/or the insertion efficiency, indicating that the fluorescence emission of this type of self-inserting dye may not be reliable for determining size or size distribution of BNPs with complex lipid compositions.- Published
- 2020
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36. Direct Measurement of Total Vesicular Catecholamine Content with Electrochemical Microwell Arrays.
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Ranjbari E, Taleat Z, Mapar M, Aref M, Dunevall J, and Ewing A
- Subjects
- Electrochemical Techniques instrumentation, Electrodes, Gold chemistry, Lab-On-A-Chip Devices, Liposomes chemistry, Microfluidic Analytical Techniques instrumentation, Catecholamines analysis, Electrochemical Techniques methods, Liposomes analysis, Microfluidic Analytical Techniques methods
- Abstract
We have designed and fabricated a microwell array chip (MWAC) to trap and detect the entire content of individual vesicles after disruption of the vesicular membrane by an applied electrical potential. To understand the mechanism of vesicle impact electrochemical cytometry (VIEC) in microwells, we simulated the rupture of the vesicles and subsequent diffusion of entrapped analytes. Two possibilities were tested: (i) the vesicle opens toward the electrode, and (ii) the vesicle opens away from the electrode. These two possibilities were simulated in the different microwells with varied depth and width. Experimental VIEC measurements of the number of molecules for each vesicle in the MWAC were compared to VIEC on a gold microdisk electrode as a control, and the quantified catecholamines between these two techniques was the same. We observed a prespike foot in a significant number of events (∼20%) and argue this supports the hypothesis that the vesicles rupture toward the electrode surface with a more complex mechanism including the formation of a stable pore intermediate. This study not only confirms that in standard VIEC experiments the whole content of the vesicle is oxidized and quantified at the surface of the microdisk electrode but actively verifies that the adsorbed vesicle on the surface of the electrode forms a pore in the vicinity of the electrode rather than away from it. The fabricated MWAC promotes our ability to quantify the content of vesicles accurately, which is fundamentally important in bioanalysis of the vesicles.
- Published
- 2020
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37. Genetic and molecular analysis of trichome development in Arabis alpina .
- Author
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Chopra D, Mapar M, Stephan L, Albani MC, Deneer A, Coupland G, Willing EM, Schellmann S, Schneeberger K, Fleck C, Schrader A, and Hülskamp M
- Subjects
- Arabidopsis Proteins genetics, Basic Helix-Loop-Helix Transcription Factors genetics, Gene Expression Regulation, Plant genetics, Morphogenesis genetics, Mutation genetics, Phenotype, Transcription Factors genetics, Arabis genetics, Trichomes genetics
- Abstract
The genetic and molecular analysis of trichome development in Arabidopsis thaliana has generated a detailed knowledge about the underlying regulatory genes and networks. However, how rapidly these mechanisms diverge during evolution is unknown. To address this problem, we used an unbiased forward genetic approach to identify most genes involved in trichome development in the related crucifer species Arabis alpina In general, we found most trichome mutant classes known in A. thaliana We identified orthologous genes of the relevant A. thaliana genes by sequence similarity and synteny and sequenced candidate genes in the A. alpina mutants. While in most cases we found a highly similar gene-phenotype relationship as known from Arabidopsis , there were also striking differences in the regulation of trichome patterning, differentiation, and morphogenesis. Our analysis of trichome patterning suggests that the formation of two classes of trichomes is regulated differentially by the homeodomain transcription factor AaGL2 Moreover, we show that overexpression of the GL3 basic helix-loop-helix transcription factor in A. alpina leads to the opposite phenotype as described in A. thaliana Mathematical modeling helps to explain how this nonintuitive behavior can be explained by different ratios of GL3 and GL1 in the two species., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
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38. Spatiotemporal Kinetics of Supported Lipid Bilayer Formation on Glass via Vesicle Adsorption and Rupture.
- Author
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Mapar M, Jõemetsa S, Pace H, Zhdanov VP, Agnarsson B, and Höök F
- Subjects
- Adsorption, Glass chemistry, Kinetics, Lipid Bilayers chemistry, Microscopy, Fluorescence, Molecular Dynamics Simulation, Monte Carlo Method, Particle Size, Surface Properties, Lipid Bilayers chemical synthesis
- Abstract
Supported lipid bilayers (SLBs) represent one of the most popular mimics of the cell membrane. Herein, we have used total internal reflection fluorescence microscopy for in-depth characterization of the vesicle-mediated SLB formation mechanism on a common silica-rich substrate, borosilicate glass. Fluorescently labeling a subset of vesicles allowed us to monitor the adsorption of individual labeled vesicles, resolve the onset of SLB formation from small seeds of SLB patches, and track their growth via SLB-edge-induced autocatalytic rupture of adsorbed vesicles. This made it possible to perform the first quantitative measurement of the SLB front velocity, which is shown to increase up to 1 order of magnitude with time. This effect can be classified as dramatic because in many other physical, chemical, or biological kinetic processes the front velocity is either constant or decreasing with time. The observation was successfully described with a theoretical model and Monte Carlo simulations implying rapid local diffusion of lipids upon vesicle rupture.
- Published
- 2018
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39. Effective Refractive Index and Lipid Content of Extracellular Vesicles Revealed Using Optical Waveguide Scattering and Fluorescence Microscopy.
- Author
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Rupert DLM, Mapar M, Shelke GV, Norling K, Elmeskog M, Lötvall JO, Block S, Bally M, Agnarsson B, and Höök F
- Subjects
- Biomarkers chemistry, Refractometry, Extracellular Vesicles chemistry, Lipids analysis, Microscopy, Fluorescence
- Abstract
Extracellular vesicles (EVs) are generating a growing interest because of the key roles they play in various biological processes and because of their potential use as biomarkers in clinical diagnostics and as efficient carriers in drug-delivery and gene-therapy applications. Their full exploitation, however, depends critically on the possibility to classify them into different subpopulations, a task that in turn relies on efficient means to identify their unique biomolecular and physical signatures. Because of the large heterogeneity of EV samples, such information remains rather elusive, and there is accordingly a need for new and complementary characterization schemes that can help expand the library of distinct EV features. In this work, we used surface-sensitive waveguide scattering microscopy with single EV resolution to characterize two subsets of similarly sized EVs that were preseparated based on their difference in buoyant density. Unexpectedly, the scattering intensity distribution revealed that the scattering intensity of the high-density (HD) population was on an average a factor of three lower than that of the low-density (LD) population. By further labeling the EV samples with a self-inserting lipid-membrane dye, the scattering and fluorescence intensities from EVs could be simultaneously measured and correlated at the single-particle level. The labeled HD sample exhibited not only lower fluorescence and scattering intensities but also lower effective refractive index ( n ≈ 1.35) compared with the LD EVs ( n ≈ 1.38), indicating that both the lipid and protein contents were indeed lower in the HD EVs. Although separation in density gradients of similarly sized EVs is usually linked to differences in biomolecular content, we suggest based on these observations that the separation rather reflects the ability of the solute of the gradient to penetrate the lipid membrane enclosing the EVs, that is, the two gradient bands are more likely because of the differences in membrane permeability than to differences in biomolecular content of the EVs.
- Published
- 2018
- Full Text
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40. Extending charge separation lifetime and distance in patterned dye-sensitized SnO 2 -TiO 2 μm-thin films.
- Author
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Saavedra Becerril V, Sundin E, Mapar M, and Abrahamsson M
- Abstract
A simple method for the preparation of patterned dye-sensitized SnO
2 -TiO2 thin films, designed to prolong the lifetime of the interfacial charge separated state is presented. Using microfluidic technology, the thin films were sensitized with the organic sensitizer D35 such that they contain SnO2 -TiO2 areas with dye and SnO2 dye-free areas at which injected electrons can be accumulated. Single wavelength transient absorption spectroscopy confirmed significantly extended charge separation lifetime at the dye-semiconductor interface. Sufficiently high density of injected electrons results in substantial decrease of charge recombination rate constants (kcr ); a factor of ∼50 compared to dye-sensitized TiO2 thin films and a factor of ∼2000 compared to dye-sensitized SnO2 thin films. Furthermore, the potential of this approach was confirmed by photoinduced conduction band mediated electron transfer from the dye to a model electron acceptor, Co protoporphyrin IX, which was adsorbed to the SnO2 -only regions.- Published
- 2017
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41. Lack of TNF-α Gene Polymorphism (rs1799724) Association with Sustained Virological Response in Iranian Patients with Chronic HCV Infection.
- Author
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Larijani MS, Bahiraei N, Nikbin M, Mohajel N, Rad LN, Baghbani F, Mapar M, and Sadat SM
- Subjects
- Adult, Alleles, Female, Gene Frequency genetics, Genotype, Hepacivirus pathogenicity, Humans, Iran, Male, Middle Aged, Genetic Predisposition to Disease genetics, Hepatitis C, Chronic genetics, Polymorphism, Single Nucleotide genetics, Tumor Necrosis Factor-alpha genetics
- Abstract
Infection with the hepatitis C virus is a major public health concern which can lead to carcinoma and liver failure. It has been shown that single nucleotide polymorphisms can affect the level of gene activity of tumor necrosis factor (TNF) which has an important role, especially in viral infections which can lead to apaptosis of infected hepatocellular cells. We investigated the impact of three possible genotypes for rs1800629 or A/G single nucleotide polymorphism located downstream of TNFα gene promoter in groups of control (n=76) and chronic hepatitis C patients (n=89) focusing on the response to treatment among sensitive and resistant groups. Genomic DNA was extracted from 500 μl prepheral whole blood and PCR and RFLP were used to amplify the region of interest and genotyping. With statistical analyzes a p-value <0.05 was considered meaningful. There was no significant difference in distribution of the possible three genotypes among healthy individuals and patients (P=0.906, OR=1.194, CI=0.063-22.790). However, the frequency of the G allele was higher in patients whereas A allele was more common among healthy individuals (p<0.0001). Further studies with more samples appears to be necessary.
- Published
- 2016
42. Correlation Study Between IL-28B Gene Polymorphism (rs8099917SNP) and Sustained Virological Response in Iranian Patients with Chronic Hepatitis C.
- Author
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Larijani MS, Sadat SM, Nikbin M, Talebi SS, Javadi F, Mohajel N, Bolhassani A, Daneshvar M, Aghasadeghi MR, Pouriayevali MH, and Mapar M
- Subjects
- Adult, Cross-Sectional Studies, Female, Genotype, Hepatitis C, Chronic virology, Humans, Interferons, Male, Middle Aged, Hepatitis C, Chronic genetics, Interleukins genetics, Polymorphism, Single Nucleotide
- Abstract
Background: The current standard treatment for hepatitis C is a combination of pegylated interferon alpha and ribavirin (peg-IFNα/RBV). Recent studies have shown that single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) gene coding for IFN-λ3 were associated with the antiviral treatment response. Therefore, in this study, we determined the distribution of the rs8099917 (T/G) polymorphism with sustained virological response (SVR) to chronic hepatitis C virus infection among Iranian patients., Methods: This cross-sectional study was performed on 150 blood samples based on 93 patients with chronic HCV genotypes 1 and 3 including 71 SVR positive, 22 negative, and 57 healthy individual controls. DNA was extracted from the samples and the frequency of the polymorphism was analyzed the using PCR-RFLP method. Finally, the products were detected on 3.5% agarose gel electrophoresis., Results: The analysis of the data for G/T polymorphism showed that the GG genotype was identified in 6 patients of 71 who achieved SVR, while the GT heterozygous was found in 33 patients and SVR was achieved in 19. Finally, the TT was detected in 53 patients and 7 patients were resistant to treatment., Conclusions: The results showed significant effects of G allele carriers on susceptibility to HCV infection com-pared to the other allele (T) in our studied population (p = 0.013, OR = 2.23, 95% CI = 1.18-4.21), but we did not find a significant correlation for SVR to therapy in patients with genotype TT (p = 0.055, OR = 0.48, 95% CI = 0.23-1.01). However, further studies with more samples are necessary.
- Published
- 2016
- Full Text
- View/download PDF
43. Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells.
- Author
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Agnarsson B, Lundgren A, Gunnarsson A, Rabe M, Kunze A, Mapar M, Simonsson L, Bally M, Zhdanov VP, and Höök F
- Subjects
- Blood Platelets cytology, Cells, Cultured, Gold chemistry, Humans, Light, Liposomes chemistry, Liposomes metabolism, Metal Nanoparticles chemistry, Scattering, Radiation, Biosensing Techniques methods, Microscopy methods, Single-Cell Analysis methods
- Abstract
Advancement in the understanding of biomolecular interactions has benefited greatly from the development of surface-sensitive bioanalytical sensors. To further increase their broad impact, significant efforts are presently being made to enable label-free and specific biomolecule detection with high sensitivity, allowing for quantitative interpretation and general applicability at low cost. In this work, we have addressed this challenge by developing a waveguide chip consisting of a flat silica core embedded in a symmetric organic cladding with a refractive index matching that of water. This is shown to reduce stray light (background) scattering and thereby allow for label-free detection of faint objects, such as individual sub-20 nm gold nanoparticles as well as sub-100 nm lipid vesicles. Measurements and theoretical analysis revealed that light-scattering signals originating from single surface-bound lipid vesicles enable characterization of their sizes without employing fluorescent lipids as labels. The concept is also demonstrated for label-free measurements of protein binding to and enzymatic (phospholipase A2) digestion of individual lipid vesicles, enabling an analysis of the influence on the measured kinetics of the dye-labeling of lipids required in previous assays. Further, diffraction-limited imaging of cells (platelets) binding to a silica surface showed that distinct subcellular features could be visualized and temporally resolved during attachment, activation, and spreading. Taken together, these results underscore the versatility and general applicability of the method, which due to its simplicity and compatibility with conventional microscopy setups may reach a widespread in life science and beyond.
- Published
- 2015
- Full Text
- View/download PDF
44. Comparison of the efficacy and safety of zinc sulfate vs. placebo in the treatment of pruritus of hemodialytic patients: a pilot randomized, triple-blind study.
- Author
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Mapar MA, Pazyar N, Siahpoosh A, Latifi SM, Beladi Mousavi SS, and Khazanee A
- Subjects
- Administration, Oral, Adult, Aged, Double-Blind Method, Female, Humans, Male, Middle Aged, Pilot Projects, Pruritus complications, Pruritus etiology, Severity of Illness Index, Sleep Wake Disorders drug therapy, Sleep Wake Disorders etiology, Time Factors, Treatment Outcome, Uremia etiology, Young Adult, Zinc Sulfate adverse effects, Pruritus drug therapy, Renal Dialysis adverse effects, Uremia drug therapy, Zinc Sulfate therapeutic use
- Abstract
Aim: Improvement of uremic pruritus has been reported under short-term administration of oral zinc sulfate. Objective of the study was to confirm efficacy and safety of oral zinc sulfate in pruritus of hemodialytic patients, Methods: A pilot randomized, triple-blind study was conducted to evaluate the pruritus of hemodialytic patients. Forty eligible patients were screened and assigned to receive either zinc sulfate (220 mg/d) or matched placebo for a 4-week trial. Pruritus scale was evaluated at the initiation of the study and 1, 2, 3, and 4 weeks after the treatment. We used a modified score proposed by Duo assessing pruritus severity, distribution of pruritus, and frequency of pruritus-related sleep disturbance., Results: Thirty-six patients completed the study. The mean pruritus score decreased in both groups during the first and the second weeks of trial; however, it was more prominent in zinc group than placebo one. In the zinc group, 4 (20%) patients showed pruritus discontinuation during treatment period whereas, in the placebo group, the number was only 1 (5%) patient. Nonetheless, T-test revealed no statistically significant difference between the zinc and placebo groups (P=0.88 and P=0.56, respectively)., Conclusion: Our findings demonstrated that oral zinc sulfate (220 mg/d) during four weeks treatment might be safe and effective in discontinuation of uremic pruritus, but it was not significant. This could be because of the small number of patients; therefore, we suggest conducting more studies with larger sample size.
- Published
- 2015
45. A comparative study of the mini-punch grafting and hair follicle transplantation in the treatment of refractory and stable vitiligo.
- Author
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Mapar MA, Safarpour M, Mapar M, and Haghighizadeh MH
- Subjects
- Adult, Biopsy, Needle, Female, Graft Rejection, Graft Survival, Humans, Iran, Male, Middle Aged, Prognosis, Prospective Studies, Risk Assessment, Severity of Illness Index, Treatment Outcome, Vitiligo diagnosis, Young Adult, Hair Follicle transplantation, Skin Pigmentation physiology, Skin Transplantation methods, Vitiligo surgery
- Abstract
Background: Some vitiligo lesions are resistant to all medical treatments., Objective: We sought to compare the efficacy of hair follicle transplantation and mini-punch grafting for the treatment of refractory vitiligo lesions., Methods: A total of 25 patients with stable and resistant vitiligo participated in the study. In each patient, a resistant vitiligo patch was divided into 2 equal parts. One part was treated with hair follicle transplantation and the other part with mini-punch grafting. Postsurgically, the recipient areas were exposed to narrowband ultraviolet B twice a week for 6 months. The diameter of the repigmentation around each graft was measured monthly., Results: At the end of the sixth month, 68% of follicle grafts, and 72% of mini-punch grafts, had repigmentation. The mean diameter of repigmentation around follicle grafts was 5 ± 1.7 mm and around punch grafts was 5.3 ± 1.6 mm. There was no significant difference between the 2 groups statistically (P = .18)., Limitations: Small sample size and short time of follow-up are limitations., Conclusions: Because the results of the 2 methods are not statistically different and mini-punch grafting is much easier to do than follicular transplantation, we recommend mini-punch grafting to treat drug-resistant vitiligo., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
46. A distinct type of palmoplantar keratoderma.
- Author
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Mohammad Ali M and Azarbaik M
- Subjects
- Child, Cornea pathology, Ear pathology, Humans, Lip pathology, Male, Mouth pathology, Foot Dermatoses pathology, Hand Dermatoses pathology, Keratoderma, Palmoplantar pathology, Skin pathology
- Abstract
Palmoplantar keratodermas (PPK) are a diverse group of disorders. We report a boy with PPK, grayish-blue hyperkeratotic lesions on the lips and peri-oral area, opacities on the lower portions of the corneas, mutilation of his right auricle and many other skin lesions.
- Published
- 2009
- Full Text
- View/download PDF
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