Run-time reconfigurable, fault-tolerant FPGA systems for space applications

Cozzi D. Run-time reconfigurable, fault-tolerant FPGA systems for space applications. Bielefeld: Universität Bielefeld; 2016.The aim of this thesis is to investigate the use of Dynamic Partial Reconfiguration (DPR) on Commercial Off-the-Shelf (COTS) FPGAs in space applications. Reconfigurable systems gained interest in a wide range of application fields, including aerospace, where electronic devices are exposed to a harsh working environment. COTS SRAM-based FPGA devices represent an interesting hardware platform for this kind of systems since they combine low cost with the possibility to utilize state-of-the-art processing power as well as the flexibility of reconfigurable hardware. FPGA architectures have high computational power and thanks to their ability to be reconfigured at run-time, they became interesting candidates for payload processing in space applications. The presented Dynamic Reconfigurable Processing Module (DRPM) has been developed to investigate the use of the DPR approach for satellite payload processing. This scalable platform combines dynamically reconfigurable FPGAs with the required avionic interfaces (e.g., SpaceWire, MIL-STD-1553B, and SpaceFibre). In particular, a novel communication interface has been developed, the Heterogeneous Multi Processor Communication Interface (HMPCI), which allows inter-process communication with small latency and low memory footprint. Current synthesis tools do not support fully the DPR capabilities of FPGAs. Therefore, this thesis introduces INDRA 2.0: an INtegrated Design flow for Reconfigurable Architectures. The key part of INDRA 2.0 is DHHarMa: a Design flow for Homogeneous Hard Macros, which generates homogeneous hard macros for Xilinx FPGAs starting from a high-level description (e.g., VHDL). In particular, the homogeneous DHHarMa router is explained in detail, providing novel terminologies and algorithms, which have enabled the generation of homogeneous routed designs. Results have been shown that Design flow for Homogeneous Hard Macros (DHHarMa) can route homogeneously a communication infrastructure utilizing just between 1% and 31% more resources than the Xilinx router, which cannot provide a homogeneous solution. Furthermore, the permanent faults that can occur on FPGAs have been investigated. This thesis presents OLT(RE)2: an on-line on-demand approach to testing permanent faults induced by radiation in reconfigurable systems used in space missions. The proposed approach relies on a test circuit and custom placer and router. OLT(RE)2 exploits DPR to place the test circuits at run-time. Its goal is to test unprogrammed areas of the FPGA before using them. Experimental results of OLT(RE)2 have shown that is possible to generate, place, and route the test circuits needed to detect on average more than 99 % of the physical wires and on average about 97 % of the programmable interconnection points of a large arbitrary region of the FPGA in a reasonable time. Moreover, the test can be run on the target device without interfering the functional behavior of the system

OLT(RE)2: an On-Line on-demand Testing approach for permanent Radiation Effects in REconfigurable systems

Reconfigurable systems gained great interest in a wide range of application fields, including aerospace, where electronic devices are exposed to a very harsh working environment. Commercial SRAM-based FPGA devices represent an extremely interesting hardware platform for this kind of systems since they combine low cost with the possibility to utilize state-of-the-art processing power as well as the flexibility of reconfigurable hardware. In this paper we present OLT(RE)2: an on-line on-demand approach to test permanent faults induced by radiation in reconfigurable systems used in space missions. The proposed approach relies on a test circuit and on custom place-and-route algorithms. OLT(RE)2 exploits partial dynamic reconfigurability offered by today’s SRAM-based FPGAs to place the test circuits at run-time. The goal of OLT(RE)2 is to test unprogrammed areas of the FPGA before using them, thus preventing functional modules of the reconfigurable system to be placed on areas with faulty resources. Experimental results have shown that (i) it is possible to generate, place and route the test circuits needed to detect on average more than 99 % of the physical wires and on average about 97 % of the programmable interconnection points of an arbitrary large region of the FPGA in a reasonable time and that (ii) it is possible to download and run the whole test suite on the target device without interfering with the normal functioning of the system

GPR35 Activation Reduces Ca2+ Transients and Contributes to the Kynurenic Acid-Dependent Reduction of Synaptic Activity at CA3-CA1 Synapses

Limited information is available on the brain expression and role of GPR35, a Gi/o coupled receptor activated by kynurenic acid (KYNA). In mouse cultured astrocytes, we detected GPR35 transcript using RT-PCR and we found that KYNA (0.1 to 100 µM) decreased forskolin (FRSK)-induced cAMP production (p<0.05). Both CID2745687 (3 µM, CID), a recently described GPR35 antagonist, and GPR35 gene silencing significantly prevented the action of KYNA on FRSK-induced cAMP production. In these cultures, we then evaluated whether GPR35 activation was able to modulate intracellular Ca(2+) concentration ([Ca(2+)]i ) and [Ca(2+)]i fluxes. We found that both KYNA and zaprinast, a phosphodiesterase (PDE) inhibitor and GPR35 agonist, did not modify either basal or peaks of [Ca(2+)]i induced by challenging the cells with ATP (30 µM). However, the [Ca(2+)]i plateau phase following peak was significantly attenuated by these compounds in a store-operated Ca(2+) channel (SOC)-independent manner. The activation of GPR35 by KYNA and zaprinast was also studied at the CA3-CA1 synapse in the rat hippocampus. Evoked excitatory post synaptic currents (eEPSCs) were recorded from CA1 pyramidal neurons in acute brain slices. The action of KYNA on GPR35 was pharmacologically isolated by using NMDA and α7 nicotinic receptor blockers and resulted in a significant reduction of eEPSC amplitude. This effect was prevented in the presence of CID. Moreover, zaprinast reduced eEPSC amplitude in a PDE5- and cGMP-independent mechanism, thus suggesting that glutamatergic transmission in this area is modulated by GPR35. In conclusion, GPR35 is expressed in cultured astrocytes and its activation modulates cAMP production and [Ca(2+)]i. GPR35 activation may contribute to KYNA effects on the previously reported decrease of brain extracellular glutamate levels and reduction of excitatory transmission

Renal Fibrosis in Lupus Nephritis

Fibrosis can be defined as a pathological process in which deposition of connective tissue replaces normal parenchyma. The kidney, like any organ or tissue, can be impacted by this maladaptive reaction, resulting in persistent inflammation or long-lasting injury. While glomerular injury has traditionally been regarded as the primary focus for classification and prognosis of lupus nephritis (LN), increasing attention has been placed on interstitial fibrosis and tubular atrophy as markers of injury severity, predictors of therapeutic response, and prognostic factors of renal outcome in recent years. This review will discuss the fibrogenesis in LN and known mechanisms of renal fibrosis. The importance of the chronicity index, which was recently added to the histological categorization of LN, and its role in predicting treatment response and renal prognosis for patients with LN, will be explored. A better understanding of cellular and molecular pathways involved in fibrosis in LN could enable the identification of individuals at higher risk of progression to chronic kidney disease and end-stage renal disease, and the development of new therapeutic strategies for lupus patients

Extended criteria donor lung reconditioning with the organ care system lung: a single institution experience

Lung transplantation is a life-saving procedure limited by donor's availability. Lung reconditioning by ex vivo lung perfusion represents a tool to expand the donor pool. In this study, we describe our experience with the OCS\u2122 Lung to assess and recondition extended criteria lungs. From January 2014 to October 2016, of 86 on-site donors evaluated, eight lungs have been identified as potentially treatable with OCS\u2122 Lung. We analyzed data from these donors and the recipient outcomes after transplantation. All donor lungs improved during OCS perfusion in particular regarding the PaO2/FiO2 ratio (from 340 mmHg in donor to 537 mmHg in OCS) leading to lung transplantation in all cases. Concerning postoperative results, primary graft dysfunction score 3 at 72 h was observed in one patient, while median mechanical ventilation time, ICU, and hospital stay were 60 h, 14 and 36 days respectively. One in-hospital death was recorded (12.5%), while other two patients died during follow-up leading to 1-year survival of 62.5%. The remaining five patients are alive and in good conditions. This case series demonstrates the feasibility and value of lung reconditioning with the OCS\u2122 Lung; a prospective trial is underway to validate its role to safely increase the number of donor lungs. \ua9 2018 Steunstichting ESO

“Clinical Stability” and Propensity Score Matching in Cardiac Surgery: is the clinical evaluation of treatment efficacy algorithmdependent in small sample size settings?

Background: Propensity score matching represents one of the most popular techniques to deal with treatment allocation bias in observational studies. However, when the number of enrolled patients is very low, the creation of matched set of subjects may highly depend on the model used to estimate individual propensity scores, undermining the stability of consequential clinical findings. In this study, we investigate the potential issues related to the stability of the matched sets created by different propensity score models and we propose some diagnostic tools to evaluate them. Methods: Matched groups of patients were created using five different methods: Logistic Regression, Classification and Regression Trees, Bagging, Random Forest and Generalized Boosted Model. Differences between subjects in the matched sets were evaluated by comparing both pre-treatment covariates and propensity score distributions. We applied our proposal to a cardio-surgical observational study that aims to compare two different procedures of cardiac valve replacement. Results: Both baseline characteristics and propensity score distributions were systematically different across matched samples of patients created with different models used to estimate propensity score. The most relevant differences were observed for the matched set created by estimating individual propensity scores with Classification and Regression Trees algorithm. Conclusion: Clinical stability of matched samples created with different statistical methods should always be evaluated to ensure reliability of final estimates. This work opens the door for future investigations that fully assess the implications of this finding

Pleural mesothelioma risk in the construction industry: a case-control study in Italy, 2000-2018

Objectives Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers. DesignCase-control study. SettingCases from the National Mesothelioma Registry (2000-2018), controls from three previous case-control studies. MethodsWe selected male PM incident cases diagnosed in 2000-2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002-2004 and 2012-2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for &gt;5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses. ResultsThe whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower. ConclusionsWe found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry

Distamycin A Inhibits HMGA1-Binding to the P-Selectin Promoter and Attenuates Lung and Liver Inflammation during Murine Endotoxemia

Background: The architectural transcription factor High Mobility Group-A1 (HMGA1) binds to the minor groove of AT-rich DNA and forms transcription factor complexes (“enhanceosomes”) that upregulate expression of select genes within the inflammatory cascade during critical illness syndromes such as acute lung injury (ALI). AT-rich regions of DNA surround transcription factor binding sites in genes critical for the inflammatory response. Minor groove binding drugs (MGBs), such as Distamycin A (Dist A), interfere with AT-rich region DNA binding in a sequence and conformation-specific manner, and HMGA1 is one of the few transcription factors whose binding is inhibited by MGBs. Objectives: To determine whether MGBs exert beneficial effects during endotoxemia through attenuating tissue inflammation via interfering with HMGA1-DNA binding and modulating expression of adhesion molecules. Methodology/Principal Findings: Administration of Dist A significantly decreased lung and liver inflammation during murine endotoxemia. In intravital microscopy studies, Dist A attenuated neutrophil-endothelial interactions in vivo following an inflammatory stimulus. Endotoxin induction of P-selectin expression in lung and liver tissue and promoter activity in endothelial cells was significantly reduced by Dist A, while E-selectin induction was not significantly affected. Moreover, Dist A disrupted formation of an inducible complex containing NF-κB that binds an AT-rich region of the P-selectin promoter. Transfection studies demonstrated a critical role for HMGA1 in facilitating cytokine and NF-κB induction of P-selectin promoter activity, and Dist A inhibited binding of HMGA1 to this AT-rich region of the P-selectin promoter in vivo. Conclusions/Significance: We describe a novel targeted approach in modulating lung and liver inflammation in vivo during murine endotoxemia through decreasing binding of HMGA1 to a distinct AT-rich region of the P-selectin promoter. These studies highlight the ability of MGBs to function as molecular tools for dissecting transcriptional mechanisms in vivo and suggest alternative treatment approaches for critical illness