51 research outputs found

    Performance of buried channel n-type MOSFETs in 0.18-μm CMOS image sensor process

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    Buried channel (BC) MOSFETs are known to have better noise performance than surface channel (SC) MOSFETs when used as source followers in modern Charge Coupled Devices (CCD). CMOS image sensors find increasing range of applications and compete with CCDs in high performance imaging, however BC transistors are rarely used in CMOS. As a part of the development of charge storage using BC CCDs in CMOS, we designed and manufactured deep depletion BC n-type MOSFETs in 0.18 μm CMOS image sensor process. The transistors are designed in a way similar to the source followers in a typical BC CCD. In this paper we report the results from their characterization and compare with enhancement mode and “zero-threshold” SC devices. In addition to the detailed current-voltage and noise measurements, semiconductor device simulation results are presented to illustrate and understand the different conditions affecting the channel conduction and the noise performance of the BC transistors at low operating voltages. We show that the biasing of the BC transistors has to be carefully adjusted for optimal operation, and that their noise performance at the right operating conditions can be superior to SC devices, despite their lower gain as in-pixel source followers

    ISIS2: Pixel Sensor with Local Charge Storage for ILC Vertex Detector

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    ISIS (In-situ Storage Imaging Sensor) is a novel CMOS sensor with multiple charge storage capability developed for the ILC vertex detector by the Linear Collider Flavour Identification (LCFI) collaboration. This paper reports test results for ISIS2, the second generation of ISIS sensors implemented in a 0.18 micron CMOS process. The local charge storage and charge transfer were unambiguously demonstrated.Comment: 11 pages, 16 figures, to be included in the Proceedings of International Linear Collider Workshop 201

    Modeling of Charge Transfer Inefficiency in a CCD with High Speed Column Parallel Readout

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    Charge Coupled Devices (CCDs) have been successfully used in several high energy physics experiments over the past two decades. Their high spatial resolution and thin sensitive layers make them an excellent tool for studying short-lived particles. The Linear Collider Flavour Identification (LCFI) collaboration is developing Column-Parallel CCDs (CPCCDs) for the vertex detector of a future Linear Collider. The CPCCDs can be read out many times faster than standard CCDs, significantly increasing their operating speed. An Analytic Model has been developed for the determination of the charge transfer inefficiency (CTI) of a CPCCD. The CTI values determined with the Analytic Model agree largely with those from a full TCAD simulation. The Analytic Model allows efficient study of the variation of the CTI on parameters like readout frequency, operating temperature and occupancy.Comment: 5 pages, 13 figures, presented on behalf of the LCFI Collaboration, proceedings IEEE 2008 Nuclear Science Symposium, Dresden, Germany, and 11th Topical Seminar on Innovative Particle and Radiation Detectors (IPRD08) 2008, Siena, Ital

    Assessing cellular efficacy of bromodomain inhibitors using fluorescence recovery after photobleaching

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    BACKGROUND: Acetylation of lysine residues in histone tails plays an important role in the regulation of gene transcription. Bromdomains are the readers of acetylated histone marks, and, consequently, bromodomain-containing proteins have a variety of chromatin-related functions. Moreover, they are increasingly being recognised as important mediators of a wide range of diseases. The first potent and selective bromodomain inhibitors are beginning to be described, but the diverse or unknown functions of bromodomain-containing proteins present challenges to systematically demonstrating cellular efficacy and selectivity for these inhibitors. Here we assess the viability of fluorescence recovery after photobleaching (FRAP) assays as a target agnostic method for the direct visualisation of an on-target effect of bromodomain inhibitors in living cells. RESULTS: Mutation of a conserved asparagine crucial for binding to acetylated lysines in the bromodomains of BRD3, BRD4 and TRIM24 all resulted in reduction of FRAP recovery times, indicating loss of or significantly reduced binding to acetylated chromatin, as did the addition of known inhibitors. Significant differences between wild type and bromodomain mutants for ATAD2, BAZ2A, BRD1, BRD7, GCN5L2, SMARCA2 and ZMYND11 required the addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) to amplify the binding contribution of the bromodomain. Under these conditions, known inhibitors decreased FRAP recovery times back to mutant control levels. Mutation of the bromodomain did not alter FRAP recovery times for full-length CREBBP, even in the presence of SAHA, indicating that other domains are primarily responsible for anchoring CREBBP to chromatin. However, FRAP assays with multimerised CREBBP bromodomains resulted in a good assay to assess the efficacy of bromodomain inhibitors to this target. The bromodomain and extraterminal protein inhibitor PFI-1 was inactive against other bromodomain targets, demonstrating the specificity of the method. CONCLUSIONS: Viable FRAP assays were established for 11 representative bromodomain-containing proteins that broadly cover the bromodomain phylogenetic tree. Addition of SAHA can overcome weak binding to chromatin, and the use of tandem bromodomain constructs can eliminate masking effects of other chromatin binding domains. Together, these results demonstrate that FRAP assays offer a potentially pan-bromodomain method for generating cell-based assays, allowing the testing of compounds with respect to cell permeability, on-target efficacy and selectivity

    Bispecific repurposed medicines targeting the viral and immunological arms of COVID-19

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    Effective agents to treat coronavirus infection are urgently required, not only to treat COVID-19, but to prepare for future outbreaks. Repurposed anti-virals such as remdesivir and human anti-inflammatories such as barcitinib have received emergency approval but their overall benefits remain unclear. Vaccines are the most promising prospect for COVID-19, but will need to be redeveloped for any future coronavirus outbreak. Protecting against future outbreaks requires the identification of targets that are conserved between coronavirus strains and amenable to drug discovery. Two such targets are the main protease (Mpro) and the papain-like protease (PLpro) which are essential for the coronavirus replication cycle. We describe the discovery of two non-antiviral therapeutic agents, the caspase-1 inhibitor SDZ 224015 and Tarloxotinib that target Mpro and PLpro, respectively. These were identified through extensive experimental screens of the drug repurposing ReFRAME library of 12,000 therapeutic agents. The caspase-1 inhibitor SDZ 224015, was found to be a potent irreversible inhibitor of Mpro (IC50 30 nM) while Tarloxotinib, a clinical stage epidermal growth factor receptor inhibitor, is a sub micromolar inhibitor of PLpro (IC50 300 nM, Ki 200 nM) and is the first reported PLpro inhibitor with drug-like properties. SDZ 224015 and Tarloxotinib have both undergone safety evaluation in humans and hence are candidates for COVID-19 clinical evaluation
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