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Space-based biomanufacturing has the potential to improve the sustainability of deep space exploration. To advance biomanufacturing, bioprocessing systems need to be developed for space applications. Here, commercial technologies were assessed to design space bioprocessing systems to supply a liquid amine carbon dioxide scrubber with active carbonic anhydrase produced recombinantly. Design workflows encompassed biomass dewatering of 1 L Escherichia coli cultures through to recombinant protein purification. Non-crew time equivalent system mass (ESM) analyses had limited utility for selecting specific technologies. Instead, bioprocessing system designs focused on minimizing complexity and enabling system versatility. Three designs that differed in biomass dewatering and protein purification approaches had nearly equivalent ESM of 357–522 kg eq. Values from the system complexity metric (SCM), technology readiness level (TRL), integration readiness level (IRL), and degree of crew assistance metric identified a simpler, less costly, and easier to operate design for automated biomass dewatering, cell lysis, and protein affinity purification.

Traumatic spinal cord injury results in the disruption of neural and vascular structures (primary injury) and is characterized by an evolution of secondary pathogenic events that collectively define the extent of functional recovery. This article reviews the vascular responses to spinal cord injury, focusing on both early and delayed events, including intraparenchymal hemorrhage, inflammation, disruption of the blood-spinal cord barrier, and angiogenesis. These vascular-related events not only influence the evolution of secondary tissue damage but also define an environment that fosters neural plasticity in the chronically injured spinal cord.

Space-based biomanufacturing has the potential to improve the sustainability of deep space exploration. To advance biomanufacturing, bioprocessing systems need to be developed for space applications. Here, commercial technologies were assessed to design space bioprocessing systems to supply a liquid amine carbon dioxide scrubber with active carbonic anhydrase produced recombinantly. Design workflows encompassed biomass dewatering of 1 L Escherichia coli cultures through to recombinant protein purification. Equivalent system mass (ESM) analyses had limited utility for selecting specific technologies. Instead, bioprocessing system designs focused on minimizing complexity and enabling system versatility. Three designs that differed in biomass dewatering and protein purification approaches had nearly equivalent ESM of 357-522 kg eq. Values from the system complexity metric (SCM), technology readiness level (TRL), and degree of crew assistance metric identified a simpler, less costly, and easier to operate design for automated biomass dewatering, cell lysis, and protein affinity purification. Competing Interest Statement The authors have declared no competing interest.

This is a textually complete and comprehensively annotated edition of the poet Arthur Hugh Clough’s letters to five of the leading American poets and scholars of his day: Ralph Waldo Emerson, Charles Eliot Norton, James Russell Lowell, Francis James Child and Henry Wadsworth Longfellow, over the period 1847–1861. Fifteen of these letters have not previously been published, and those that appear in published editions are largely incomplete and unannotated. The letters in this edition have been transcribed from the original manuscripts held at the Bodleian and Houghton Libraries. They provide a great deal of valuable information about the less well-known later period of Clough’s life and have been extensively annotated to modern scholarly standards using information from primary literary and historical sources. The introduction to the thesis contextualises Clough’s visit to America and the initiation of the correspondence with his American friends, highlighting the central importance of the ‘American dimension’ to Clough’s life and work. I also discuss aspects of nineteenth-century letter-writing that have only relatively recently become the subject of critical attention, such as the impact of material factors – postage rates, steamship schedules, etc – on Clough’s transatlantic correspondence. Clough’s creation of an ‘epistolary self’ in his private letters, together with his distinctive habit of writing ‘journal-letters’ and the idea of letters as historical ‘testimony’ are the subject of detailed analysis, and I draw a number of parallels with his use of the epistolary form in his major poetry. Chapter 2 of the thesis evaluates existing ‘theories’ of annotation, reviews current practice in relation to the annotation of nineteenth-century correspondence and concludes with a reflection on my own experience of editing Clough’s letters. The absence of a definitive version of Clough’s American letters and the comprehensive introduction will make this edition an original contribution to scholarly work on nineteenth-century correspondence and poetry.

The aetiology of methaemoglobinaemia may be congenital due to deficiency in cytochrome b5 reductase and to structural abnormalities in the haemoglobin molecule (haemoglobin M disorders) or be acquired as the result of drug treatment or the presence of toxins-most commonly nitrites or nitrates. Life threatening methaemoglobinaemia is rare and is usually the result of acute poisoning by drugs or toxins. 2 We report life threatening methaemoglobinaemia associated with sodium nitrite in three previously healthy siblings, 4 year old twin boys (cases 1 and 2) and their sister aged 2 years (case 3).

While traveling to deep space is difficult for many reasons, food is a crucial one. Round-trip Mars mission scenarios last 3 years, demanding food with a shelf-life of 5 years; this means that feeding human crew sustainably for long-duration missions beyond low Earth orbit (LEO) will ultimately lead to a paradigm shift away from the current Earth-based food production system, which depends upon storing and transporting prepackaged foods, and toward bio-regenerative production of food in space. Pharmaceuticals and nutritional supplements face similar challenges. Moreover, the methods we currently use to detect dangerous microbes in food require sample return to Earth, a situation not viable for deep-space missions. While the science behind generating foods and bioproducts is covered by other white papers, in this paper we discuss a crucial gap uniting all of them: how to ensure that such products are free of unwanted microbial contamination and safe for crew to consume. Because Earth-based food safety systems cannot be directly applied in space, safety assurance is currently a critical bottleneck in the space production of food and other bioproducts. Future sustainable deep-space missions will require NASA to devote more resources in the coming decade to understanding the biological and physical science principles underlying microbial food safety in space, and to developing efficient, reliable methods in this area.

Because I'm not an expert, I probably ask the questions that people want to hear.

In December in Padstow in North Cornwall - there's a small gallery devoted to local painters and it featured lots of great wild Cornish seascapes. Tell us about the next cultural thing you're planning to do. I'm going to see whatever production the Northern Ballet Theatre bring to Wales - they're a fantastic dance company.

Thrombin activity is a factor in acute central nervous system trauma and may contribute to such chronic neurodegenerative disorders as Alzheimer's disease. Immediately produced at sites of vascular damage, thrombin catalyzes the final steps in blood coagulation and induces many inflammatory and wound repair responses, including responses from neural cells. In this study, we examined the mechanisms underlying thrombin-induced protection of astrocytes from hypoglycemia and thrombin-induced cell death in astrocytes and neurons. We determined that thrombin-induced cell death was mediated by activation of the thrombin receptor, and involved apoptosis. A battery of pharmacological agents was employed to determine the involvement of specific signal transduction proteins in both pathways. Tyrosine and serine/threonine kinases and the small GTP-ase RhoA appear to be involved in both pathways. Thrombin treatment increases available RhoA activity during both the apoptotic and protective treatments, but the increase is greater and more rapid in thrombin-induced cell death. A time course study of thrombin-induced cell death revealed that, unlike the protective pathway, prolonged exposure to thrombin was required to induce cell death. Thus the cell death and protective pathways may share initial signaling proteins, but differences in the amplitude as well as the duration of the signal may result in different cellular response. Protease Nexin-1 (PN-1) is a potent inhibitor of thrombin, urokinase and plasmin. Located primarily in the brain, PN-1 surrounds capillaries and blood vessels and is thought to protect the brain from extravasated thrombin activity. PN-1 has been shown to bind to the extracellular matrix, and this binding increased thrombin inhibition by PN-1, whilst decreasing inhibition of urokinase and plasmin by PN-1. Studies using purified extracellular matrix proteins were performed to determine which component of the matrix was responsible for the change in target specificity of PN-1. Only collagen IV decreased complex formation between PN-1 and urokinase and plasmin, and decreased rate of inhibition of these proteases by PN-1 without affecting inhibition of thrombin by PN-1. Binding and co-immunoprecipitation of PN-1 and collagen IV was also analyzed.