27 research outputs found

    Correction:Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction between CYP2D6 and opioids (codeine, tramadol and oxycodone) (European Journal of Human Genetics, (2021), 10.1038/s41431-021-00920-y)

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    The Data statement was partly wrong and should have read as below. DATA AVAILABILITY All data and material are either included in the Supplementary information or publicly available (i.e., the published articles, PubMed). The guidelines and background information are available on the website of the Royal Dutch Pharmacists Association (KNMP) (Pharmacogenetic Recommendations. Available from: https://www.knmp.nl/). The guidelines and background information will be available on PharmGKB.org

    Mixed autologous leukocytes reactions performed using matured CML dendritic cells and CDS or CD4 T-cells results in colony inhibition only with CD4 cultured with IL-12 throughout and is not leukemia specific

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    CD34+ cells were isolated from the initial aphérèses from 3 CML patients before any treatment. All these patient had the b3a2 junction and MHC complexes for which CTL generation had been described using peptides (A2, DR201 - A2, DR1101 -All, DR2). DCs were generated from cytaphereses from the same patients, harvested when they had normalized their counts to have a sufficient proportion of monocytes. DCs were generated by classical adherence enrichment followed by a 6 days culture in RPMI, autologous serum 2%, GM-CSF and IL-4. At day 6. CD40L was added to mature the DCs, which were harvested for the MLRs after 48 hrs. We first assess the functional capacity of CML DCs using immunophenotyping, allogeneic and autologous proliferative tests and specificic antigen (Influenza) presentation in short MLR followed by ELISPOT assays. We could conclude that these DCs were functionally normal. We then performed autologous MLRs: mature DCs and responder cells (ratiol/10) were cultured the first week in RPMI, autologous serum 10%, IL-12 and 1L-6. Three types of responders were used (CDS, CDS + CD4 and CD4). The mixture CD8/CD4 was used to test for a potential help] effect. In one half of the conditions, IL-12 was added throughout the 6 weeks culture which led to six different culture conditions. IL-12 was added to reverse potential tolerance. The cells were restimulated each week by the same DCs and cultured with IL2 and IL-7, +/- IL 12. At the end, T-cells from the mixed CD8/CD4 cultures were separated into CD4 and CDS cells, to assess the potential of CD8+ cells cultured in the presence of CD4+ cells. T-cells were then co-cultured with CD34-positive cells for 24 hrs with IL2, SCF, IL3 and GCS-F. They were then seeded in a soft agar CFU-GM inhibition assay. After 2 weeks, colonies were counted and individual colonies tested for BCR-ABL expression using RT-PCR. Results: a significant (50%) inhibition of the number of colonies was observed only when CD4+ cells, from the MLRs with IL-12 added throughout, were co-cultured with CD34+ cells. However, the proportion of Ph+/Ph- colonies was unchanged in comparison with the control. We conclude that in our experimental conditions, inhibition of colonies occurs only when CD4+ cells, cultured with IL-12 throughout the whole MLR, are used. This inhibition is not leukemic specific and seems to be directed against autologous hematological determinants. None of our patients being HLA A3 or B8 positive, the absence of CDS response should be interpreted with caution. However, our observations should lead to careful reflection when designing immunotherapy protocols in CML patients.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Impact of calibrated band-tails on the subthreshold swing of pocketed TFETs

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    © 2018 IEEE. The tunnel field-effect transistor (TFET) is one of the prime steep-slope device candidates to be employed in future ultra-low power logic applications [1], [2], and can achieve sub-60 mV/dec subthreshold swings (SS) using quantum mechanical (QM) band-to-band tunneling (BTBT). One of the main challenges for TFETs is obtaining a sufficiently high drive-current I ON [1]. The I ON can be enhanced by introducing a highly-counter-doped pocket at the tunnel junction [3], [4]. However, it is well known that high doping concentrations introduce band-tails states in the bandgap [5]. First assessments on band-tails in TFETs, linked to diode measurements, have been made [6]-[8]. However, it is unknown whether the band-tails-induced tunneling contributions limit the performance of optimized pocketed TFETs. In this work, we investigate the impact of band-tails on the SS of p-n-i-n In 0.53 Ga 0.47 As and InAs TFETs for different pocket thicknesses and doping concentrations in the source and pocket, while using band-tails density-of-states (DOS) obtained from successful diode calibrations [8].status: publishe

    Signature of Ballistic Band-Tail Tunneling Current in Tunnel FET

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    Signature of Ballistic Band-Tail Tunneling Current in Tunnel FET

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    Calibration of the high-doping induced ballistic band-tails tunneling current in In0.53Ga0.47As Esaki diodes

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    © 2017 IEEE. I. Introduction The growing demand for power efficient devices has accelerated the research into the use of the tunnel field-effect transistor (TFET) in future ultra-low power applications because of its promising potential for sub-60 mV/dec subthreshold swing achieved through quantum mechanical band-To-band tunneling (BTBT) [1]-[3]. Unfortunately, a significant gap between theoretical predictions and experiments remains to be bridged [2]. Considerable efforts are being made to develop models for some of the main causes of suboptimal TFET performance such as trap-Assisted tunneling (TAT) [4], [5], phonon-Assisted tunneling (PAT) [6], and Auger generated leakage currents [7]. However, aside from qualitative analyses [8] and purely predictive work on the device impact of tunneling transitions involving high-doping induced band-Tails states in InSb nanowire TFETs [9] and 2D-TFETs [10], no attempts have been made to calibrate these contributions. This work aims to fill this gap by developing and calibrating an approximate ballistic semi-classical (SC) model for high-doping induced band-Tails using the experimental I-V data of In0.53Ga0.47As p-i-n Esaki diodes [11]. The hypothesis is posited that the mismatch between measurement and simulation in the negative differential resistance regime (see Fig. 1), which cannot be explained by SC TAT models, is caused by ballistic band-Tails tunneling. The calibration thus gives an upper limit to the band-Tails current. Lastly, the impact of band-Tails on the performance of a p-n-i-n TFET is investigated.status: publishe

    Phonon-assisted tunneling in direct-bandgap semiconductors

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    © 2018 Author(s). In tunnel field-effect transistors, trap-assisted tunneling (TAT) is one of the probable causes for degraded subthreshold swing. The accurate quantum-mechanical (QM) assessment of TAT currents also requires a QM treatment of phonon-assisted tunneling (PAT) currents. Therefore, we present a multi-band PAT current formalism within the framework of the quantum transmitting boundary method. An envelope function approximation is used to construct the electron-phonon coupling terms corresponding to local Fröhlich-based phonon-assisted inter-band tunneling in direct-bandgap III-V semiconductors. The PAT current density is studied in up to 100 nm long and 20 nm wide p-n diodes with the 2- and 15-band material description of our formalism. We observe an inefficient electron-phonon coupling across the tunneling junction. We further demonstrate the dependence of PAT currents on the device length, for our non-self-consistent formalism which neglects changes in the electron distribution function caused by the electron-phonon coupling. Finally, we discuss the differences in doping dependence between direct band-to-band tunneling and PAT current.status: publishe

    Self-consistent procedure including envelope function normalization for full-zone Schrodinger-Poisson problems with transmitting boundary conditions

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    © 2018 Author(s). In the quantum mechanical simulation of exploratory semiconductor devices, continuum methods based on a k ⋅p/envelope function model have the potential to significantly reduce the computational burden compared to prevalent atomistic methods. However, full-zone k ⋅p/envelope function simulation approaches are scarce and existing implementations are not self-consistent with the calculation of the electrostatic potential due to the lack of a stable procedure and a proper normalization of the multi-band envelope functions. Here, we therefore present a self-consistent procedure based on a full-zone spectral k ⋅p/envelope function band structure model. First, we develop a proper normalization for the multi-band envelope functions in the presence of transmitting boundary conditions. This enables the calculation of the free carrier densities. Next, we construct a procedure to obtain self-consistency of the carrier densities with the electrostatic potential. This procedure is stabilized with an adaptive scheme that relies on the solution of Poisson’s equation in the Gummel form, combined with successive underrelaxation. Finally, we apply our procedure to homostructure In 0.53Ga 0.47As tunnel field-effect transistors (TFETs) and staggered heterostructure GaAs 0.5Sb 0.5/In 0.53Ga 0.47As TFETs and show the importance of self-consistency on the device predictions for scaled dimensions.status: publishe

    Peripheral blood stem cell contamination in mantle cell non-Hodgkin lymphoma: the case for purging?

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    Intensification using peripheral blood stem cells collected after chemotherapy followed by growth factors is being increasingly investigated as an alternative to conventional chemotherapy for mantle cell non-Hodgkin lymphoma. We investigated 14 grades III-IV, t(11;14)-positive cases for contamination of PBSC collected after a polychemotherapy regimen followed by G-CSF. Patients were first treated with a polychemotherapy regimen. There were four CR, seven PR, two refractory and one early death. Seven patients have been transplanted, in whom PBSC were mobilized, using either cyclophosphamide/VP16 or Dexa-BEAM followed by G-CSF. For all patients, whether actually autografted or not, PB cells were tested at the time of regeneration on G-CSF after the first polychemotherapy or after the mobilizing regimen. PCR evaluation of contamination was performed first by a semi-quantitative approach, using serial dilutions of initial DNA, then confirmed using a limiting-dilution analysis. Two patients were not informative (one early death and one without an available molecular marker). PB cells collected at regeneration contained at least one log more lymphoma cells than steady-state blood or marrow, apart from in two cases. Moreover, where a mobilizing treatment diminished tumor burden in the patient, at the same time it increased PB contamination in most cases. We conclude that advanced mantle cell NHL appears to be largely resistant to significant in vivo purging by conventional chemotherapy. Where treatment brings benefits by reducing tumor load, it may at the same time negate it by mobilizing malignant cells into the collections used to intensify. Although the clonogenic potential of this massive infiltration is unknown (only gene marking studies could provide a definitive answer regarding the source of relapses), strategies aimed at reducing the level of contamination in the graft should be considered when designing future protocols.Journal Articleinfo:eu-repo/semantics/publishe
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