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- Das, A., et al.
(författare)
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Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:1, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion–deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10–100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in ‘immunologically cold’ tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy. © 2022, The Author(s).
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| 3. |
- Dickstein, D. L., et al.
(författare)
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Brain and blood biomarkers of tauopathy and neuronal injury in humans and rats with neurobehavioral syndromes following blast exposure
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 5940-5954
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is a risk factor for the later development of neurodegenerative diseases that may have various underlying pathologies. Chronic traumatic encephalopathy (CTE) in particular is associated with repetitive mild TBI (mTBI) and is characterized pathologically by aggregation of hyperphosphorylated tau into neurofibrillary tangles (NFTs). CTE may be suspected when behavior, cognition, and/or memory deteriorate following repetitive mTBI. Exposure to blast overpressure from improvised explosive devices (IEDs) has been implicated as a potential antecedent for CTE amongst Iraq and Afghanistan Warfighters. In this study, we identified biomarker signatures in rats exposed to repetitive low-level blast that develop chronic anxiety-related traits and in human veterans exposed to IED blasts in theater with behavioral, cognitive, and/or memory complaints. Rats exposed to repetitive low-level blasts accumulated abnormal hyperphosphorylated tau in neuronal perikarya and perivascular astroglial processes. Using positron emission tomography (PET) and the [F-18]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [F-18]AV1451 at the white/gray matter junction in frontal, parietal, and temporal brain regions, a typical localization of CTE tauopathy. We also observed elevated levels of neurofilament light (NfL) chain protein in the plasma of veterans displaying excess [F-18]AV1451 retention. These findings suggest an association linking blast injury, tauopathy, and neuronal injury. Further study is required to determine whether clinical, neuroimaging, and/or fluid biomarker signatures can improve the diagnosis of long-term neuropsychiatric sequelae of mTBI.
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| 5. |
- Kermaniha, M., et al.
(författare)
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Systematic optimization of phosphorous diffusion for solar cell application
- 2016
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Ingår i: Journal of materials science. Materials in electronics. - : Springer-Verlag New York. - 0957-4522 .- 1573-482X. ; 27:12, s. 13086-13092
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Tidskriftsartikel (refereegranskat)abstract
- Fossil fuel storage is running low and scientists around the globe are involved in a big search for an optimized substitute. Photovoltaic is one of the most likely alternatives to solve this issue and replace the fossil fuels. Among all types of cells, silicon solar cells are the most economical ones to produce affordable energy. In this paper, a systematic study was done on the diffusion of phosphorous in multi-crystalline silicon during solar cell emitter formation. All parameters involved in the conversion of a multi-crystalline p-type silicon to a p-n junction were analyzed quantitatively. This systematic approach predicts the effect of inputs on the outputs which decreases the number of the trail runs. The analysis result indicate, that raising the diffusion temperature from 830 to 880 A degrees C decreases the sheet resistance by -100 Omega/sq, and increasing POCl3 flow from 300 to 500 SCCM has an effect of -21 Omega/sq.
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| 7. |
- Ebrahimi, P., et al.
(författare)
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Systematic Optimization of Boron Diffusion for Solar Cell Emitters
- 2017
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Ingår i: Journal of Electronic Materials. - : Springer. - 0361-5235 .- 1543-186X. ; 46:7, s. 4236-4241
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Tidskriftsartikel (refereegranskat)abstract
- To achieve p-n junctions for n-type solar cells, we have studied BBr3 diffusion in an open tube furnace, varying parameters of the BBr3 diffusion process such as temperature, gas flows, and duration of individual process steps, i.e., predeposition and drive-in. Then, output parameters such as carrier lifetime, sheet resistance, and diffusion profile were measured and statistically analyzed to optimize the emitter characteristics. Statistical analysis (factorial design) was finally employed to systematically explore the effects of the set of input variables on the outputs. The effect of the interactions between inputs was also evaluated for each output, quantified using a two-level factorial method. Temperature and BBr3 flow were found to have the most significant effect on different outputs such as carrier lifetime, junction depth, sheet resistance, and final surface concentration.
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| 8. |
- Kharrazi, S. M., et al.
(författare)
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Pretreatment of lignocellulosic waste as a precursor for synthesis of high porous activated carbon and its application for Pb (II) and Cr (VI) adsorption from aqueous solutions
- 2021
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier. - 0141-8130 .- 1879-0003. ; 180, s. 299-310
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Tidskriftsartikel (refereegranskat)abstract
- Effects of Elm tree sawdust pretreatments using alkali and alkaline earth metals (NaCl, KCl, CaCl2, MgCl2 and Elm tree ash) and deashing solutions (water, HCl, HNO3 and aqua regia) before the carbonization process on the porosity of produced activated carbons and Pb (II) and Cr (VI) adsorption were studied. The activated carbons were characterized by pore size distribution, surface area, FTIR, and SEM-EDX analysies. Based on the results, HCl leaching pretreatment of the biomass increased the activated carbon adsorption capacity of Cr (VI) from 114 to 190 mg g−1. The treatment of biomass with alkali and alkali earth metal salts, especially MgCl2, remarkably increased the activated carbon adsorption capacity of Pb (II) from 233 to 1430 mg g−1. The results indicated that Pb (II) adsorption was attributed to both the mesoporous structure of activated carbon and the abundance of Mg on the activated carbon's surface. On the other hand, the micropores played a major role in Cr (VI) adsorption capacity. The development of the micro- or mesoporous structure of activated carbons through pretreatment of lignocellulosic precursor could be an approach for providing high performance activated carbons for Pb (II) and Cr (VI) removal from aqueous solutions.
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