Fault-tolerant multichannel demultiplexer subsystems

Fault tolerance in future processing and switching communication satellites is addressed by showing new methods for detecting hardware failures in the first major subsystem, the multichannel demultiplexer. An efficient method for demultiplexing frequency slotted channels uses multirate filter banks which contain fast Fourier transform processing. All numerical processing is performed at a lower rate commensurate with the small bandwidth of each bandbase channel. The integrity of the demultiplexing operations is protected by using real number convolutional codes to compute comparable parity values which detect errors at the data sample level. High rate, systematic convolutional codes produce parity values at a much reduced rate, and protection is achieved by generating parity values in two ways and comparing them. Parity values corresponding to each output channel are generated in parallel by a subsystem, operating even slower and in parallel with the demultiplexer that is virtually identical to the original structure. These parity calculations may be time shared with the same processing resources because they are so similar

Codes for protection from synchronization loss and additive errors

Codes for protection from synchronization loss and additive error

Fault tolerance in space-based digital signal processing and switching systems: Protecting up-link processing resources, demultiplexer, demodulator, and decoder

Fault tolerance features in the first three major subsystems appearing in the next generation of communications satellites are described. These satellites will contain extensive but efficient high-speed processing and switching capabilities to support the low signal strengths associated with very small aperture terminals. The terminals' numerous data channels are combined through frequency division multiplexing (FDM) on the up-links and are protected individually by forward error-correcting (FEC) binary convolutional codes. The front-end processing resources, demultiplexer, demodulators, and FEC decoders extract all data channels which are then switched individually, multiplexed, and remodulated before retransmission to earth terminals through narrow beam spot antennas. Algorithm based fault tolerance (ABFT) techniques, which relate real number parity values with data flows and operations, are used to protect the data processing operations. The additional checking features utilize resources that can be substituted for normal processing elements when resource reconfiguration is required to replace a failed unit

Glucuronides in the gut: Sugar-driven symbioses between microbe and host

The intestinal milieu is astonishingly complex and home to a constantly changing mixture of small and large molecules, along with an abundance of bacteria, viral particles, and eukaryotic cells. Such complexity makes it difficult to develop testable molecular hypotheses regarding host-microbe interactions. Fortunately, mammals and their associated gastrointestinal (GI) microbes contain complementary systems that are ideally suited for mechanistic studies. Mammalian systems inactivate endobiotic and xenobiotic compounds by linking them to a glucuronic acid sugar for GI excretion. In the GI tract, the microbiota express β-glucuronidase enzymes that remove the glucuronic acid as a carbon source, effectively reversing the actions of mammalian inactivation. Thus, by probing the actions of microbial β-glucuronidases, and by understanding which substrate glucuronides they process, molecular insights into mammalian-microbial symbioses may be revealed amid the complexity of the intestinal tract. Here, we focus on glucuronides in the gut and the microbial proteins that process them

The Microbiota, Chemical Symbiosis, and Human Disease

Our understanding of mammalian-microbial mutualism has expanded by combing microbial sequencing with evolving molecular and cellular methods, and unique model systems. Here, the recent literature linking the microbiota to diseases of three of the key mammalian mucosal epithelial compartments – nasal, lung and gastrointestinal (GI) tract – is reviewed with a focus on new knowledge about the taxa, species, proteins and chemistry that promote health and impact progression toward disease. The information presented is further organized by specific diseases now associated with the microbiota:, Staphylococcus aureus infection and rhinosinusitis in the nasal-sinus mucosa; cystic fibrosis (CF), chronic obstructive pulmonary disorder (COPD), and asthma in the pulmonary tissues. For the vast and microbially dynamic GI compartment, several disorders are considered, including obesity, atherosclerosis, Crohn’s disease, ulcerative colitis, drug toxicity, and even autism. Our appreciation of the chemical symbiosis ongoing between human systems and the microbiota continues to grow, and suggest new opportunities for modulating this symbiosis using designed interventions

Immobilization of active human carboxylesterase 1 in biomimetic silica nanoparticles

The encapsulation of proteins in biomimetic silica has recently been shown to successfully maintain enzymes in their active state. Organophosphate (OP) compounds are employed as pesticides as well as potent chemical warfare nerve agents. Because these toxicants are life threatening, we sought to generate biomimetic silicas capable of responding to OPs. Here, we present the silica encapsulation of human drug metabolism enzyme carboxylesterase 1 (hCE1) in the presence of a range of catalysts. hCE1 was successfully encapsulated into silica particles when lysozyme or the peptide R5 were used as catalysts; in contrast, polyethyleneimine (PEI), a catalyst employed to encapuslate other enzymes, did not facilitate hCE1 entrapment. hCE1 silica particles in a column chromatography format respond to the presence of the organophosphate (OP) pesticides paraoxon and dimethyl-p-nitrophenyl phosphate in solution. These results may lead to novel approaches to detect OP pesticides or other weaponized agents that bind hCE1

Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice

The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial β-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8-(piperazin-1-yl)-1,2,3,4-tetrahydro-[1,2,3]triazino[4′,5′:4,5]thieno[2,3-c]isoquinolin-5-yl)morpholine (UNC10201652, Inh 9) was administered to mice to selectively inhibit a narrow range of bacterial β-glucuronidases in the gut. The metabolomic profiles of the intestinal contents, biofluids, and several tissues involved in the enterohepatic circulation were measured and compared to control animals. No biochemical perturbations were observed in the plasma, liver or gall bladder. In contrast, the metabolite profiles of urine, colon contents, feces and gut wall were altered compared to the controls. Changes were largely restricted to compounds derived from gut microbial metabolism. This work establishes that inhibitors targeted towards bacterial β-glucuronidases modulate the functionality of the intestinal microbiota without adversely impacting the host metabolic system

The human microbiome is a source of therapeutic drug targets

It was appreciated early in drug discovery that the microbiota play an important role in the efficacy of therapeutic compounds. Indeed, the first antibiotic sulfa drugs were shown in the 1940s to be transformed by the bacteria that encode what we now call the intestinal microbiome. Here we briefly review the roles symbiotic bacteria play in the chemistry of human health, and we focus on the emerging appreciation that specific enzyme targets expressed by microbial symbiotes can be selectively disrupted to achieve clinical outcomes. We conclude that components of the microbiome should be considered “druggable targets,” and we suggest that our rapidly evolving understanding of the chemical biology of mammalian-microbial symbiosis will translate into improved human health

Mammalian short palate lung and nasal epithelial clone 1 (SPLUNC1) in pH-dependent airway hydration

The epithelia that line the conducting airways are the lung’s first point of contact with inhaled pathogens and toxicants. As such, they are known to play an important role in the lung’s innate defense system, which includes (i) the production of airway surface liquid (ASL) that helps cleanse the airways through the physical removal of pathogens and toxicants on the mucociliary escalator and (ii) the secretion of anti-microbial proteins into the ASL to kill inhaled pathogens. Interestingly, the recently crystallized short palate lung and nasal epithelial clone 1 (SPLUNC1) protein appears to be a multi-functional protein. That is, it not only acts as an anti-microbial agent, but also modulates ASL homeostasis by acting as an endogenous inhibitor of the epithelial Na+ channel (ENaC). This review will focus on the latter function of SPLUNC1, and will discuss new structural and physiological data regarding SPLUNC1’s failure to function as a regulator of ASL hydration in CF airways