23 research outputs found
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The Reliability of FPGA circuit designs in the presence of radiation induced configuration upsets
FPGAs are an appealing solution for space-based remote sensing applications. However, an a low-earth orbit, FPGAs are susceptible t o Single-Event Upsets (SEUs). In an effort to understand the effects of SEUs, an SEU simulator based on the SLAAC-1V computing board has been developed. This simulator artifically upsets the conjiguration memory of an FPGA and measures its impact on FPGA designs. The accuracy of this simulation environment has been verified using ground-based radiation testing. This sim{approx}ulataon tool is being used to characterize the reliabilitg of SEU mitigation techniques for PI'GAs
FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni
Schistosomes are amongst the most important and neglected pathogens in the world, and schistosomiasis control relies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuromuscular function remain largely unknown. Short amidated neuropeptides, FMRFamide-like peptides (FLPs), are distributed abundantly throughout the nervous system of every flatworm examined and they produce potent myoexcitation. Our goal here was to determine the mechanism by which FLPs elicit contractions of schistosome muscle fibers. Contraction studies showed that the FLP Tyr-Ile-Arg-Phe-amide (YIRFamide) contracts the muscle fibers through a mechanism that requires Ca2+ influx through sarcolemmal voltage operated Ca2+ channels (VOCCs), as the contractions are inhibited by classical VOCC blockers nicardipine, verapamil and methoxyverapamil. Whole-cell patch-clamp experiments revealed that inward currents through VOCCs are significantly and reversibly enhanced by the application of 1 µM YIRFamide; the sustained inward currents were increased to 190% of controls and the peak currents were increased to 180%. In order to examine the biochemical link between the FLP receptor and the VOCCs, PKC inhibitors calphostin C, RO 31–8220 and chelerythrine were tested and all produced concentration dependent block of the contractions elicited by 1 µM YIRFamide. Taken together, the data show that FLPs elicit contractions by enhancing Ca2+ influx through VOCC currents using a PKC-dependent pathway
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Hardness by design technique for field programmable gate arrays.
FPGAs are an attractive alternative for many space-based computing operations. While radiation hardened FPGAs are available, SRAM-based FPGAs are susceptible to Single-Event Upsets (SEUs). Several FPGA design hardening techniques are investigated to improve the reliability of FPGA designs operating in a radiation environment. The improved design reliability provided by these techniques are measured using a single-event upset simulation environment
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Validation of an FPGA fault simulator.
This work describes the radiation testing of a fault simulation tool used to study the behavior of FPGA circuits in the presence of configuration memory upsets . There is increasing interest in the use of Field Programmable Gate Arrays (FPGAs) in space-based applications such as remote sensing[1] . The use of reconfigurable Field Programmable Gate Arrays (FPGAs) within a spacecraft allows the use of digital circuits that are both application-specific and reprogrammable. Unlike application-specific integrated circuits (ASICs), FPGAs can be configured after the spacecraft has been launched . This flexibility allows the same FPGA resources to be used for multiple instruments, missions, or changing spacecraft objectives . Errors in an FPGA design can be resolved by fixing the incorrect design and reconfiguring the FPGA with an updated configuration bitstream . Further, custom circuit designs can be created to avoid FPGA resources that have failed during the course of the spacecraft mission
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SEU mitigation for half-latches in xilinx virtex FPGAs.
The performance, in-system reprogrammability, flexibility, and reduced costs of SRAM-based field-programmable gate arrays (FPGAs) make them very interesting for high-speed, on-orbit data processing, but, because the current generation of radiation-tolerant SRAM-based FPGAs are derived directly from COTS versions of the chips, their memory structures are still susceptible to single-event upsets (SEUs) . While previous papers have described the SEU characteristics and mitigation techniques for the configuration and user memory structures on the Xilinx Virtex family of FPGAs, we will concentrate on the effects of SEUs on 'half-latch' structures within the Virtex architecture, describe techniques for mitigating these effects, and provide new experimental data which illustrate the effectiveness of one of these mitigation techniques under proton radiation
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Reconfigurable computing in space: from current technology to reconfigurable systems-on-a-chip.
The performance, in-system reprogrammability, flexibility, and reduced costs of SRAM-based FPGAs make them very interesting for high-speed, on-orbit data processing, but, because the current generation of radiation-tolerant SRAM-based FPGAs are derived directly from COTS versions of the chips, several issues must be dealt with for space, including SEU sensitivities, power consumption, thermal problems, and support logic. This paper will discuss Los Alamos National Laboratory's approach to using the Xilinx XQVR1000 FPGAs for on-orbit processing in the Cibola Flight Experiment (CFE) as well as the possibilities and challenges of using newer, system-on-a-reprogrammable-chip FPGAs, such as Virtex I1 Pro, in space-based reconfigurable computing. The reconfigurable computing payload for CFE includes three processing boards, each having three radiation-tolerant Xilinx XQVRl 000 FPGAs. The reconfigurable computing architecture for this project is intended for in-flight, real-time processing of two radio fi-equency channels, each producing 12-bit samples at 100 million samples/second. In this system, SEU disruptions in data path operations can be tolerated while disruptions in the control path are much less tolerable. With this system in mind, LANL has developed an SEU management scheme with strategies for handling upsets in all of the FPGA resources known to be sensitive to radiation-induced SEUs. While mitigation schemes for many resources will be discussed, the paper will concentrate on SEU management strategies and tools developed at LANL for the configuration bitstream and 'half latches'. To understand the behavior of specific designs under SEUs in the configuration bitstream, LANL and Brigham Young University have developed an SEU simulator using ISI's SLAACl-V reconfigurable computing board. The simulator can inject single-bit upsets into a design's configuration bitstream to simulate SEUs and observe how these simulated SEUs affect the design's operation. Using fast partial configuration, the simulator can cover the entire bitstream of a Xilinx XQVRl 000 FPGA, which has 6 million configuration bits, in about 30 minutes. Instead of using a combination of TMR and configuration scrubbing for bitstream SEU mitigation, the approach developed for CFE uses minimal logic redundancy along with an SEU detection and correction scheme to handle bitstream SEUs. Though this approach allows some SEUs to affect less critical user logic, it requires considerably fewer FPGA resources than TMR and allows bitstream SEU rates to be monitored. 'Half latches', another class of SEU sensitive FPGA state elements, are used to provide logic constants in user FPGA designs but are not explicitly controlled by the configuration bitstream. Upsets in half latches cannot be detected by readback nor corrected via configuration repair or scrubbing - only a full reconfiguration can reliably restore their state. We have created a tool, called RadDRC, which can replace all critical half latches with more visible and correctable constant sources. Lastly, in looking forward, this paper will briefly consider the possible benefits and risks of using reconfigurable system-on-a-chip FPGAs, such as the Virtex II Pro, for reconfigurable computing in space. The paper concludes with a summary of challenges for using reconfigurable computing in space and a summary of future research at LANL in this area
Isoforms of MUC16 activate oncogenic signaling through EGF receptors to enhance the progression of pancreatic cancer
Aberrant expression of CA125/MUC16 is associated with pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. However, knowledge of the contribution of MUC16 to pancreatic tumorigenesis is limited. Here, we show that MUC16 expression is associated with disease progression, basal-like and squamous tumor subtypes, increased tumor metastasis, and short-term survival of PDAC patients. MUC16 enhanced tumor malignancy through the activation of AKT and GSK3β oncogenic signaling pathways. Activation of these oncogenic signaling pathways resulted in part from increased interactions between MUC16 and epidermal growth factor (EGF)-type receptors, which were enhanced for aberrant glycoforms of MUC16. Treatment of PDAC cells with monoclonal antibody (mAb) AR9.6 significantly reduced MUC16-induced oncogenic signaling. mAb AR9.6 binds to a unique conformational epitope on MUC16, which is influenced by O-glycosylation. Additionally, treatment of PDAC tumor-bearing mice with either mAb AR9.6 alone or in combination with gemcitabine significantly reduced tumor growth and metastasis. We conclude that the aberrant expression of MUC16 enhances PDAC progression to an aggressive phenotype by modulating oncogenic signaling through ErbB receptors. Anti-MUC16 mAb AR9.6 blocks oncogenic activities and tumor growth and could be a novel immunotherapeutic agent against MUC16-mediated PDAC tumor malignancy
Leucine aminopeptidase of the human blood flukes, Schistosoma mansoni and Schistosoma japonicum
An array of schistosome endoproteases involved in the digestion of host hemoglobin to absorbable peptides has been described, but the exoprotease responsible for catabolising these peptides to amino acids has yet to be identified. By searching the public databases we found that Schistosoma mansoni and Schistosoma japonicum express a gene encoding a member of the M17 family of leucine aminopeptidases (LAPs). A functional recombinant S. mansoni LAP produced in insect cells shared biochemical properties, including pH optimum for activity, substrate specificity and reliance on metal cations for activity, with the major aminopeptidase activity in soluble extracts of adult worms. The pH range in which the enzyme functions and the lack of a signal peptide indicate that the enzyme functions intracellularly. Immunolocalisation studies showed that the S. mansoni LAP is synthesised in the gastrodermal cells surrounding the gut lumen. Accordingly, we propose that peptides generated in the lumen of the schistosome gut are absorbed into the gastrodermal cells and are cleaved by LAP to free amino acids before being distributed to the internal tissues of the parasite. Since LAP was also localised to the surface tegument it may play an additional role in surface membrane re-modelling