Manufacturing processes

The following issues are covered: process development frequently lags behind material development, high fabrication costs, flex joints (bellows) - a continuing program, SRM fabrication-induced defects, and in-space assembly will require simplified design

Sphagnum physiology in the context of changing climate: emergent influences of genomics, modelling and host-microbiome interactions on understanding ecosystem function.

Peatlands harbour more than one-third of terrestrial carbon leading to the argument that the bryophytes, as major components of peatland ecosystems, store more organic carbon in soils than any other collective plant taxa. Plants of the genus Sphagnum are important components of peatland ecosystems and are potentially vulnerable to changing climatic conditions. However, the response of Sphagnum to rising temperatures, elevated CO2 and shifts in local hydrology have yet to be fully characterized. In this review, we examine Sphagnum biology and ecology and explore the role of this group of keystone species and its associated microbiome in carbon and nitrogen cycling using literature review and model simulations. Several issues are highlighted including the consequences of a variable environment on plant-microbiome interactions, uncertainty associated with CO2 diffusion resistances and the relationship between fixed N and that partitioned to the photosynthetic apparatus. We note that the Sphagnum fallax genome is currently being sequenced and outline potential applications of population-level genomics and corresponding plant photosynthesis and microbial metabolic modelling techniques. We highlight Sphagnum as a model organism to explore ecosystem response to a changing climate and to define the role that Sphagnum can play at the intersection of physiology, genetics and functional genomics

CIAS-DM: A Model-Based, Human-Centered Architectural Modeling Method + Tool

A recent trend in architecture is for the built environment pro-actively contributes to enhancing human health, well-being, performance, and social interactions in measurable, predictable, and adaptable ways. Buildings are becoming interfaces and digital machines and their roles and capabilities are expanding. Accommodating this trend will require architectural design methods and tools to evolve. Sensing, monitoring, actuation, intelligence, and communication subsystems are now integral components of environmental designers’ vocabularies and considerations when designing space and form. At present, the theories, methods, and tools for representing and incorporating these elements during design do not exist. Developing these artifacts is an active area of research. This dissertation focuses on representing the affordances of complex, interactive, architectural systems (CIAS) and proposes, evaluates, and refines the Complex, Interactive, Architectural Systems Design Methodology (CIAS-DM). The purpose of CIAS-DM is to aid designers in making sure they understand the design challenge well at the start of the project. The Validation Square Research Design is used to evaluate CIAS-DM. Results are preliminary, but indicate that using a method similar to CIAS-DM may be useful for helping designers manage the scope of complex,interactive design challenges

The prepower stroke conformation of myosin V

eW have used electron microscopy and single-particle image processing to study head conformation in myosin V molecules. We find that in the presence of ATP, many heads have a sharply angled conformation that is rare in its absence. The sharply angled conformation is similar to a myosin II atomic structure proposed to mimic the prepower stroke state. The leading head in molecules attached to actin by both heads has a similar conformation, but is also sharply angled in a second plane by tethering through the trail head. The lead head lever joins the motor domain ∼5 nm axially from where it joins the trail motor. These positions locate the converter subdomain and show the lead motor is in the prepower stroke conformation. Tethering by the trail head places the lead head motor domain at the correct axial position along the actin for binding, but at the wrong orientation. Attachment is achieved either by bending the lead head lever throughout its length or at the pliant point. The microscopy shows that most of the walking stride is produced by changes in lever angle brought about by converter movement, but is augmented by distortion produced by thermal energy

Structures of smooth muscle myosin and heavy meromyosin in the folded, shutdown state

Remodelling of the contractile apparatus within smooth muscle cells is an essential process that allows effective contractile activity over a wide range of cell lengths. The thick filaments may be redistributed via depolymerisation into inactive myosin monomers that have been detected in vitro, in which the long tail has a folded conformation. The structure of this folded molecule has been controversial. Using negative stain electron microscopy of individual folded molecules from turkey gizzard we show they are more compact than previously described, with heads and the three segments of the folded tail closely packed. Smooth muscle heavy meromyosin (HMM), which lacks two-thirds of the tail, closely resembles the equivalent parts of whole myosin. Image processing reveals a characteristic head region morphology for both HMM and myosin whose features are identifiable by comparison with less compact molecules. The two heads associate asymmetrically: the tip of one motor domain touches the base of the other, resembling the blocked and free heads of this HMM when it forms 2-D crystals on lipid. The tail of HMM lies between the heads, contacting the blocked motor domain, unlike in the 2-D crystal. The tail of the intact myosin is bent sharply and consistently at two positions close to residues 1175 and 1535. The first bend position correlates with a skip in the coiled coil sequence, the second does not. The first segment runs between the heads from the head-tail junction. Unexpectedly, the other segments associate only with the blocked head rather than both heads, such that the second bend lies at a specific position near the C-lobe of the blocked head regulatory light chain. Quantitative analysis of tail flexibility shows that the single coiled coil of HMM has an apparent Young’s modulus of about 0.5 GPa. The folded tail of the intact molecule is less flexible indicating interactions between the segments. The folded tail does not modify the compact head arrangement but stabilises it, indicating a structural mechanism for the very low ATPase activity of the folded molecule

Flexibility within the Heads of Muscle Myosin-2 Molecules

We show that negative-stain electron microscopy and image processing of nucleotide-free (apo) striated muscle myosin-2 subfragment-1 (S1), possessing one light chain or both light chains, is capable of resolving significant amounts of structural detail. The overall appearance of the motor and the lever is similar in rabbit, scallop and chicken S1. Projection matching of class averages of the different S1 types to projection views of two different crystal structures of apo S1 shows that all types most commonly closely resemble the appearance of the scallop S1 structure rather than the methylated chicken S1 structure. Methylation of chicken S1 has no effect on the structure of the molecule at this resolution: it too resembles the scallop S1 crystal structure. The lever is found to vary in its angle of attachment to the motor domain, with a hinge point located in the so-called pliant region between the converter and the essential light chain. The chicken S1 crystal structure lies near one end of the range of flexion observed. The Gaussian spread of angles of flexion suggests that flexibility is driven thermally, from which a torsional spring constant of ~ 23 pN·nm/rad2 is estimated on average for all S1 types, similar to myosin-5. This translates to apparent cantilever-type stiffness at the tip of the lever of 0.37 pN/nm. Because this stiffness is lower than recent estimates from myosin-2 heads attached to actin, we suggest that binding to actin leads to an allosteric stiffening of the motor–lever junction

From Top to Bottom - the Multiwavelength Campaign of V824 Ara (HD 155555)

A great deal of progress has been made in recent years in decomposing the 2-D structure in the atmospheres of late-type stars. Doppler images of many photospheres single stars, T Tauri stars, Algols, RS CV(sub n) binaries to name a few - are regularly published (Strassmeier 1996; Richards and Albright 1996; Rice and Strassmeier 1996; Kuerster et al. 1994). Ultraviolet spectral images of chromospheres appear in the literature (e.g., Walter et al. 1987; Neff et al. 1989) but are less common owing to the difficult nature of obtaining complete phase coverage. Zeeman doppler images of magnetic fields are now feasible (e.g., Donati et al. 1992). Performing Doppler imaging of the same targets over many seasons has also been accomplished (e.g, Vogt et al. 1997). Even when a true image reconstruction is not possible due to poor spectral resolution, we can still infer a great deal about spatial structure if enough phases are observed. However, it is increasingly apparent that to make sense of recent results, many different spectral features spanning a range of formation temperature and density must be observed simultaneously for a coherent picture to emerge. Here we report on one such campaign. In 1996, we observed the southern hemisphere RS CV(sub n) binary V824 Ara (P=1(sup d).68, G5IV+K0V-IV-IV) over one complete stellar rotation with the Hubble Space Telescope and EUVE. In conjunction, radio and optical photometry and spectroscopy were obtained from the ground. Unique to this campaign is the complete phase coverage of a number of activity proxy indicators that cover source temperatures ranging from the photosphere to the corona

Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: The ARIPI randomized trial

Context: Even though red blood cells (RBCs) are lifesaving in neonatal intensive care, transfusing older RBCs may result in higher rates of organ dysfunction, nosocomial infection, and length of hospital stay. Objective: To determine if RBCs stored for 7 days or less compared with usual standards decreased rates of major nosocomial infection and organ dysfunction in neonatal intensive care unit patients requiring at least 1 RBC transfusion. Design, Setting, and Participants: Double-blind, randomized controlled trial in 377 premature infants with birth weights less than 1250 g admitted to 6 Canadian tertiary neonatal intensive care units between May 2006 and June 2011. Intervention: Patients were randomly assigned to receive transfusion of RBCs stored 7 days or less (n=188) vs standard-issue RBCs in accordance with standard blood bank practice (n=189). Main Outcome Measures: The primary outcome was a composite measure of major neonatal morbidities, including necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, and intraventricular hemorrhage, as well as death. The primary outcome was measured within the entire period of neonatal intensive care unit stay up to 90 days after randomization. The rate of nosocomial infection was a secondary outcome. Results: The mean age of transfused blood was 5.1 (SD, 2.0) days in the fresh RBC group and 14.6 (SD, 8.3) days in the standard group. Among neonates in the fresh RBC group, 99 (52.7%) had the primary outcome compared with 100 (52.9%) in the standard RBC group (relative risk, 1.00; 95% CI, 0.82-1.21). The rate of clinically suspected infection in the fresh RBC group was 77.7% (n=146) compared with 77.2% (n=146) in the standard RBC group (relative risk, 1.01; 95% CI, 0.90-1.12), and the rate of positive cultures was 67.5% (n=127) in the fresh RBC group compared with 64.0% (n=121) in the standard RBC group (relative risk, 1.06; 95% CI, 0.91-1.22). Conclusion: In this trial, the use of fresh RBCs compared with standard blood bank practice did not improve outcomes in premature, very low-birth-weight infants requiring a transfusion. Trial Registration: clinicaltrials.gov Identifier: NCT00326924; Current Controlled Trials Identifier: ISRCTN65939658. ©2012 American Medical Association. All rights reserved

Synergy in anti-malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density.

Anti-malarial pre-erythrocytic vaccines (PEV) target transmission by inhibiting human infection but are currently partially protective. It has been posited, but never demonstrated, that co-administering transmission-blocking vaccines (TBV) would enhance malaria control. We hypothesized a mechanism that TBV could reduce parasite density in the mosquito salivary glands, thereby enhancing PEV efficacy. This was tested using a multigenerational population assay, passaging Plasmodium berghei to Anopheles stephensi mosquitoes. A combined efficacy of 90.8% (86.7-94.2%) was observed in the PEV +TBV antibody group, higher than the estimated efficacy of 83.3% (95% CrI 79.1-87.0%) if the two antibodies acted independently. Higher PEV efficacy at lower mosquito parasite loads was observed, comprising the first direct evidence that co-administering anti-sporozoite and anti-transmission interventions act synergistically, enhancing PEV efficacy across a range of TBV doses and transmission intensities. Combining partially effective vaccines of differing anti-parasitic classes is a pragmatic, powerful way to accelerate malaria elimination efforts