Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34+ cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT. Twenty-two individuals (median follow-up 15.4 years) were treated in the context of clinical development or named patient program. Nineteen patients were treated post-marketing authorization (median follow-up 3.2 years), and two additional patients received mobilized peripheral blood CD34+ cell GT. At data cutoff, all 43 patients were alive, with a median follow-up of 5.0 years (interquartile range 2.4-15.4) and 2 years intervention-free survival (no need for long-term enzyme replacement therapy or allogeneic hematopoietic stem cell transplantation) of 88% (95% confidence interval 78.7-98.4%). Most adverse events/reactions were related to disease background, busulfan conditioning or immune reconstitution; the safety profile of the real world experience was in line with premarketing cohort. One patient from the named patient program developed a T cell leukemia related to treatment 4.7 years after GT and is currently in remission. Long-term persistence of multilineage gene-corrected cells, metabolic detoxification, immune reconstitution and decreased infection rates were observed. Estimated mixed-effects models showed that higher dose of CD34+ cells infused and younger age at GT affected positively the plateau of CD3+ transduced cells, lymphocytes and CD4+ CD45RA+ naive T cells, whereas the cell dose positively influenced the final plateau of CD15+ transduced cells. These long-term data suggest that the risk-benefit of GT in ADA remains favorable and warrant for continuing long-term safety monitoring. Clinical trial registration: NCT00598481 , NCT034786

The investigation of magnetic levitation performances of single grain YBCO at different temperatures

Celik, Sukru/0000-0002-6918-7569; GUNER, SAIT BARIS/0000-0001-7487-4817WOS: 000397994700032The temperature dependence of the magnetic levitation force has been investigated for single-grain YBCO bulk sample, 20 mm in diameter with a thickness of 8 mm, fabricated by top-seeded melt growth (TSMG) method using Nd123 seeded. the superconducting properties of the single grain YBCO bulk are studied by VSM (Vibrating Sample Magnetometer), the microstructures and the phase constituents of those that are seen by SEM (Scanning Electron Microscope) and XRD (X-ray Diffraction). the measurements of superconducting properties indicated that magnetic levitation forces of the sample were found 11.23, 10.81, 10.34, 9.23 and 7.02 N at the temperatures of 37, 47, 57, 67 and 77, respectively, and the values of the onset critical temperature (Tc) and the zero-field critical current density (Jc) are 89.3 K and 5.6 x 10(4) A/cm(2) at 77 K, respectively. This research is intended to help for the large scale superconductor levitation performances at different temperatures. (C) 2017 Elsevier B. V. All rights reserved.Recep Tayyip Erdogan University Scientific Research Projects Coordination Department [2014.102.01.05]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [110T622]All the authors would like to thank Dr. Hari Babu Nadendla (at Brunel University, London, UK) for the sample preparation method developed by him, Dr. Yunhua Shi (at Cambridge University, Cambridge, UK) and Kenta Nakazato (at Shibaura Institute of Technology, Tokyo, Japan) for his support and encouragement. This research was supported by the Recep Tayyip Erdogan University Scientific Research Projects Coordination Department (Project Number: 2014.102.01.05). All the magnetic levitation force measurements were performed in the MLFMS designed by the project of TUBITAK (Project Number: 110T622) and whose patent application number is 2013/13638 for the Turkish Patent Institute (TPE)

The effect of stand structure on litter decomposition in Pinus sylvestris L. stands in Turkey

center dot Key message Canopy closure and stand age significantly affected the litter decomposition. Therefore, stand-specific decomposition constants (k) should be calculated in forest carbon models for more accurate carbon budget estimation. Furthermore, to reduce the carbon release from decomposing litter, regeneration cutting should be carried out at later ages, and heavy thinning should not be implemented in mature as well as overmature stands. center dot Context Decomposition of litter has an important role in primary production with its influence on nutrient release for plant uptake and carbon flux in forest ecosystems. Thus, understanding the effects of the intervention on litter decomposition is crucial for carbon management in forestry. center dot Aims The effects of stand structure and exposure on litter decomposition rate in Pinus sylvestris stands were investigated. center dot Methods Samples were taken from young to overmature stands with open to dense canopy. The litterbag method was used to measure the mass loss of the litter. The k values were calculated from the mass loss of decaying litter. Carbon and nitrogen contents of the litter were determined. center dot Results Cutting caused the decomposition to accelerate at a rate of up to 58% depending on its intensity. The k values were found to fluctuate over time from 0.189 in moderately dense-canopied stands to 0.317 in open-canopied overmature stands. Stand basal area, incubation time, and remaining carbon concentration of the litter accounted for 75% of the variation in the k value. center dot Conclusion Changes in the stand structure affect the litter decomposition rate in forest ecosystems. Heavy thinning can alter the litter decomposition process drastically, while moderate thinning may not have a clear effect in the long run

The comparison of levitation and lateral force of bulk and cut-pasted bulk GdBCO samples at different temperatures

Celik, Sukru/0000-0002-6918-7569; GUNER, SAIT BARIS/0000-0001-7487-4817; Ozturk, Kemal/0000-0002-8847-1880; ABDIOGLU, MURAT/0000-0002-5497-0817WOS: 000512377800117In this work, in the first time, we have investigated the levitation and lateral force properties of bulk and cut-pasted bulk GdBCO samples at different temperatures and different cooling heights (CH) to determine the effect of cut-pasted process on the magnetic levitation force behaviour. the measurements of superconducting characteristics indicated that the attractive and repulsive force values of cut-pasted GdBCO sample are slightly lesser than those of GdBCO bulk sample. the maximum repulsive and attractive force values obtained as 15.45 N and -4.56 N for GdBCO bulk and as 14.78 N and -3.92 N for cut-pasted GdBCO samples at 37 K. Although there are many fabrication methods as melt-textured growth (MTG), top seeded infiltration growth (TSIG) and TSMG to produce large HTS samples, the desired large sample size and the sample shape compatible with the superconducting magnetic bearing systems are not still sufficient for the technological applications. in this study, the performed cut-pasted process and obtained magnetic levitation force data can be using for the increment sample size and the desired sample shape in the needed different geometry and size for superconducting magnetic bearing systems. (C) 2020 Elsevier B.V. All rights reserved.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [110T622]I would like to thank Prof. Dr. Hari Babu Nadendla (at Brunel University London, UK), Dr. Yunhua Shi and Prof. Dr. David Cardwell (at Cambridge University, Cambridge, UK) for their support and encouragement. All the magnetic levitation force measurements were carried out in the MLFMS made by the project of the Scientific and Technological Research Council of Turkey (TUBITAK) Project No: 110T622 (Patent application number is 2013/13638)

Lateral Force Measurements for (Gd123)(1-x) :(Gd211) (x) Superconductors at Different Temperatures

Cansiz, Ahmet/0000-0002-3988-6561; GUNER, SAIT BARIS/0000-0001-7487-4817; Ozturk, Kemal/0000-0002-8847-1880WOS: 000399178700028The lateral levitation force between melt-textured (Gd123)(1-x) :(Gd211) (x) bulk superconductors for x = 0.0, 0.1, 0.2, 0.3, 0.4, and 0.5 and a permanent magnet is measured at 30, 40, 50, 60, and 77 K under zero-field-cooling and field-cooling conditions. the variations on the observed levitation force are correlated to the varied content of Gd211 in these melt-textured samples.Recep Tayyip Erdogan University Scientific Research Projects Coordination Department [2012.102.01.1]This research was supported by the Recep Tayyip Erdogan University Scientific Research Projects Coordination Department (project number: 2012.102.01.1). All the magnetic levitation force measurements were performed in the MLFMS designed by the project of TUBITAK (project number: 110T622) and whose patent application number is 2013/13638 for the Turkish Patent Institute (TPE)