Imaging Probe for Charged Particle Detection

Single Photon Avalanche Diodes (SPADs) are semiconductor devices that detect individual photons. However, they can also experience dark count rate (DCR), generating avalanche current even when no photons are present, which limits their ability to detect low-level signals. SPADs characterization is important to gain insight into their behavior and improve their performance for various applications. This thesis discusses the development of a portable detection probe that uses the APIX2LF chip, which contains arrays of SPADs that were produced using a 150 nm standard CMOS process. A prototype board, that includes a battery, front-end electronics, and a microcontroller acting as the interface between the sensor and the PC was developed and tested using a beta-emitting source. Additionally, custom firmware was designed for the microcontroller and an automatic data acquisition framework was developed for the characterization of the DCR of six APIX2LF chips at different bias voltages and temperatures.This thesis discusses the development of a portable detection probe that uses the APIX2LF chip, which contains arrays of SPADs that were produced using a 150 nm standard CMOS process. A prototype board, that includes a battery, front-end electronics, and a microcontroller acting as the interface between the sensor and the PC was developed and tested using a beta-emitting source. Additionally, custom firmware was designed for the microcontroller and an automatic data acquisition framework was developed for the characterization of the DCR of six APIX2LF chips at different bias voltages and temperatures

Modelling and Test Generation for Crosstalk Faults in DSM Chips

In the era of deep submicron technology (DSM), many System-on-Chip (SoC) applications require the components to be operating at high clock speeds. With the shrinking feature size and ever increasing clock frequencies, the DSM technology has led to a well-known problem of Signal Integrity (SI) more especially in the connecting layout design. The increasing aspect ratios of metal wires and also the ratio of coupling capacitance over substrate capacitance result in electrical coupling of interconnects which leads to crosstalk problems. In this thesis, first the work carried out to model the crosstalk behaviour between aggressor and victim by considering the distributed RLGC parameters of interconnect and the coupling capacitance and mutual conductance between the two nets is presented. The proposed model also considers the RC linear models of the CMOS drivers and receivers. The behaviour of crosstalk in case of under etching problem has been studied and modelled by distributing and approximating the defect behaviour throughout the nets. Next, the proposed model has also been extended to model the behaviour of crosstalk in case of one victim is influenced by several aggressors by considering all aggressors have similar effect (worst-case) on victim. In all the above cases simulation experiments were also carried out and compared with well-known circuit simulation tool PSPICE. It has been proved that the generated crosstalk model is faster and the results generated are within 10% of error margin compared to latter simulation tool. Because of the accuracy and speed of the proposed model, the model is very useful for both SoC designers and test engineers to analyse the crosstalk behaviour. Each manufactured device needs to be tested thoroughly to ensure the functionality before its delivery. The test pattern generation for crosstalk faults is also necessary to test the corresponding crosstalk faults. In this thesis, the well-known PODEM algorithm for stuck-at faults is extended to generate the test patterns for crosstalk faults between single aggressor and single victim. To apply modified PODEM for crosstalk faults, the transition behaviour has been divided into two logic parts as before transition and after transition. After finding individually required test patterns for before transition and after transition, the generated logic vectors are appended to create transition test patterns for crosstalk faults. The developed algorithm is also applied for a few ISCAS 85 benchmark circuits and the fault coverage is found excellent in most circuits. With the incorporation of proposed algorithm into the ATPG tools, the efficiency of testing will be improved by generating the test patterns for crosstalk faults besides for the conventional stuck-at faults. In generating test patterns for crosstalk faults on single victim due to multiple aggressors, the modified PODEM algorithm is found to be more time consuming. The search capability of Genetic Algorithms in finding the required combination of several input factors for any optimized problem fascinated to apply GA for generating test patterns as generating the test pattern is also similar to finding the required vector out of several input transitions. Initially the GA is applied for generating test patterns for stuck-at faults and compared the results with PODEM algorithm. As the fault coverage is almost similar to the deterministic algorithm PODEM, the GA developed for stuck-at faults is extended to find test patterns for crosstalk faults between single aggressor and single victim. The elitist GA is also applied for a few ISCAS 85 benchmark circuits. Later the algorithm is extended to generate test patterns for worst-case crosstalk faults. It has been proved that elitist GA developed in this thesis is also very useful in generating test patterns for crosstalk faults especially for multiple aggressor and single victim crosstalk faults

Understanding metabolic robustness of Escherichia coli using genetic and environmental perturbations

Metabolism provides the essential biochemical intermediates and energy that enable life and its growth. In this thesis we studied robustness of Escherichia coli metabolism, by perturbing it with different methods and measuring the response at a molecular level. In Chapter 1, we introduce the latest insight into metabolic regulation and optimality in microbial model organisms. Overall, we identified and described two major gaps in knowledge: the limited amount of known metabolite-protein interactions and the unknown objectives towards which cells optimize their enzyme levels. Moreover, we provide a short introduction to the relevant methods utilized in this thesis. In Chapter 2, we describe a series of experiments which confirmed that CRISPRi is a reliable tool to specifically perturb metabolism in E. coli. We showcase the advantage of using a CRISPRi system integrated in the genome, which is suitable to apply inducible knockdowns of essential genes. We demonstrate this by characterizing growth for a library of over 100 strains and verifying inducibility and specificity with proteomics data. In Chapter 3 we applied the validated CRISPRi setup to perturb and study metabolism systematically. First, we used a pooled CRISPRi library to knock down all metabolic genes in E. coli. By following the appearance of growth defects with next generation sequencing, we show that metabolic enzymes are expressed at higher levels than strictly necessary. We then focused on a panel of 30 CRISPRi strains and characterize their response to lower enzyme levels with metabolomics and proteomics. We show that the metabolome can buffer perturbations of enzyme levels in two different stages: first, metabolites increase enzyme activity to maintain optimal growth and only later they activate gene regulatory feedbacks to specifically upregulate perturbed pathways. In Chapter 4 we employed a different approach to perturb bacterial metabolism, by growing E. coli in different environmental conditions and measuring the response at the metabolome level. We could show that in exponentially growing cells key biosynthetic products as amino acids and nucleotides are kept at relatively stable levels across different environments. We compared our dataset to a matching published proteomics dataset, showing that unlike the proteome, metabolite levels are independent from growth effects

Defect-based testing of LTS digital circuits

A Defect-Based Test (DBT) methodology for Superconductor Electronics (SCE) is presented in this thesis, so that commercial production and efficient testing of systems can be implemented in this technology in the future. In the first chapter, the features and prospects for SCE have been presented. The motivation for this research and the outline of the thesis were also described in Chapter 1. It has been shown that high-end applications such as Software-Defined Radio (SDR) and petaflop computers which are extremely difficult to implement in top-of-the-art semiconductor technologies can be realised using SCE. But, a systematic structural test methodology had yet to be developed for SCE and has been addressed in this thesis. A detailed introduction to Rapid Single-Flux Quantum (RSFQ) circuits was presented in Chapter 2. A Josephson Junction (JJ) was described with associated theory behind its operation. The JJ model used in the simulator used in this research work was also presented. RSFQ logic with logic protocols as well as the design and implementation of an example D-type flip-flop (DFF) was also introduced. Finally, advantages and disadvantages of RSFQ circuits have been discussed with focus on the latest developments in the field. Various techniques for testing RSFQ circuits were discussed in Chapter 3. A Process Defect Monitor (PDM) approach was presented for fabrication process analysis. The presented defect-monitor structures were used to gather measurement data, to find the probability of the occurrence of defects in the process which forms the first step for Inductive Fault Analysis (IFA). Results from measurements on these structures were used to create a database for defects. This information can be used as input for performing IFA. "Defect-sprinkling" over a fault-free circuit can be carried out according to the measured defect densities over various layers. After layout extraction and extensive fault simulation, the resulting information will indicate realistic faults. In addition, possible Design-for-Testability (DfT) schemes for monitoring Single-Flux Quantum (SFQ) pulses within an RSFQ circuit has also been discussed in Chapter 3. The requirement for a DfT scheme is inevitable for RSFQ circuits because of their very high frequency of operation and very low operating temperature. It was demonstrated how SFQ pulses can be monitored at an internal node of an SCE circuit, introducing observability using Test-Point Insertion (TPI). Various techniques were discussed for the introduction of DfT and to avoid the delay introduced by the DfT structure if it is required. The available features in the proposed design for customising the detector make it attractive for a detailed DBT of RSFQ circuits. The control of internal nodes has also been illustrated using TPI. The test structures that were designed and implemented to determine the occurrence of defects in the processes can also be used to locate the position for the insertion of the above mentioned DfT structures

Quantitative proteomics of the tobacco pollen tube secretome identifies novel pollen tube guidance proteins important for fertilization

List of primers used in this study. (XLSX 12 kb

Regulation of SCF TIR1/AFB E3 ligase assembly by S-nitrosylation of Arabidopsis SKP1-like1 impacts on auxin signaling

The F-box proteins (FBPs) TIR1/AFBs are the substrate recognition subunits of SKP1–cullin–F-box (SCF) ubiquitin ligase complexes and together with Aux/IAAs form the auxin co-receptor. Although tremendous knowledge on auxin perception and signaling has been gained in the last years, SCFTIR1/AFBs complex assembly and stabilization are emerging as new layers of regulation. Here, we investigated how nitric oxide (NO), through S-nitrosylation of ASK1 is involved in SCFTIR1/AFBs assembly. We demonstrate that ASK1 is S-nitrosylated and S-glutathionylated in cysteine (Cys) 37 and Cys118 residues in vitro. Both, in vitro and in vivo protein-protein interaction assays show that NO enhances ASK1 binding to CUL1 and TIR1/AFB2, required for SCFTIR1/AFB2 assembly. In addition, we demonstrate that Cys37 and Cys118 are essential residues for proper activation of auxin signaling pathway in planta. Phylogenetic analysis revealed that Cys37 residue is only conserved in SKP proteins in Angiosperms, suggesting that S-nitrosylation on Cys37 could represent an evolutionary adaption for SKP1 function in flowering plants. Collectively, these findings indicate that multiple events of redox modifications might be part of a fine-tuning regulation of SCFTIR1/AFBs for proper auxin signal transduction.This work has been supported by grants from CONICET (PIP 0202 to M.C.T), Universidad Nacional de Mar del Plata and Agencia Nacional de Promoción Científica y Tecnológica, -Argentina (PICT 1167 to M.C.T and PICT 2421 to C.A.C); from the Spanish Government (PS09/00101 and PI12/00875 to A.M.R., cofinanced by the European Union ERDF), and by the Argentinian-Spanish Integrated Action ES/11/02 / PRIAIBAR- 2011-0782. A.M.R. is supported by the I3SNS programme (ISCIII, Spanish Government). The Proteomics Service of the CBMSO is a member of Proteored (PRB2-ISCIII), and is supported by grants PT13/ 0001/0024 and PT17/0019/0018 of Spanish Government (cofinanced by the European Union ERDF). Work in the laboratory of M.E is supported by grants from the National Institutes of Health (NIH) GM43644, The Howard Hughes Medical Institute and the Gordon and Betty Moore Foundation, US

A direct path to dependable software

What would it take to make software more dependable? Until now, most approaches have been indirect: some practices – processes, tools or techniques – are used that are believed to yield dependable software, and the argument for dependability rests on the extent to which the developers have adhered to them. This article argues instead that developers should produce direct evidence that the software satisfies its dependability claims. The potential advantages of this approach are greater credibility (since the argument is not contingent on the effectiveness of the practices) and reduced cost (since development resources can be focused where they have the most impact)