Low Cost Production Of Proinsulin In Tobacco And Lettuce Chloroplasts For Injectable Or Oral Delivery Of Functional Insulin And

Current treatment for type I diabetes includes delivery of insulin via injection or pump, which is highly invasive and expensive. The production of chloroplast-derived proinsulin should reduce cost and facilitate oral delivery. Therefore, tobacco and lettuce chloroplasts were transformed with the cholera toxin B subunit fused with human proinsulin (A, B, and C peptides) containing three furin cleavage sites (CTB-PFx3). Transplastomic lines were confirmed for site-specific integration of transgene and homoplasmy. Old tobacco leaves accumulated proinsulin up to 47% of total leaf protein (TLP). Old lettuce leaves accumulated proinsulin up to 53% TLP. Accumulation was so stable that up to ~40% proinsulin in TLP was observed even in senescent and dried lettuce leaves, facilitating their processing and storage in the field. Based on the yield of only monomers and dimers of proinsulin (3 mg/g leaf, a significant underestimation), with a 50% loss of protein during the purification process, one acre of tobacco could yield up to 20 million daily doses of insulin per year. Proinsulin from tobacco leaves was purified up to 98% using metal affinity chromatography without any His-tag. Furin protease cleaved insulin peptides in vitro. Oral delivery of unprocessed proinsulin bioencapsulated in plant cells or injectable delivery into mice showed reduction in blood glucose levels similar to processed commercial insulin. C-peptide should aid in longterm treatment of diabetic complications including stimulation of nerve and renal functions. Hyper-expression of functional proinsulin and exceptional stability in dehydrated leaves offer a low cost platform for oral and injectable delivery of cleavable proinsulin

Spatial and temporal variation in penetrative strain during compression: Insights from analog models

Penetrative strain constitutes the proportion of the total shortening across an orogen that is not accommodated by the development of macroscale structures such as folds and thrusts. The accommodation of shortening by penetrative strain is widely considered to be an important process during compression, but variation in the distribution of penetrative strain during a deformation sequence is not well understood. This study provides some first-order constraints on magnitude, timing, and distribution of penetrative strain during deformation. Eight simple models, each with a geometrically and mechanically similar starting configuration, within the limits of sandbox models, were shortened to different amounts. Model results indicate first that penetrative strain increases with depth in any given model, and second that the proportion of the total shortening accommodated by penetrative strain varies with time. As the deforming wedge approaches stability, penetrative strain is highest just before initiation of a new thrust fault, after which the penetrative strain component abruptly decreases. Each model also contains a foreland zone of penetrative strain, in which penetrative strain decreases exponentially away from the deformation front. These results are consistent with available field data. Restoration of a seismic-scale cross section indicates that model results can be used to predict the amount of penetrative strain and thus the true total shortening across a deformed region. Estimates of this type may be made for additional cross sections and may provide answers to the problem of “missing shortening” across orogens and the total amount of shortening experienced at collisional plate margins

Spatial and temporal variation in penetrative strain during compression: Insights from analog models

Penetrative strain constitutes the proportion of the total shortening across an orogen that is not accommodated by the development of macroscale structures such as folds and thrusts. The accommodation of shortening by penetrative strain is widely considered to be an important process during compression, but variation in the distribution of penetrative strain during a deformation sequence is not well understood. This study provides some first-order constraints on magnitude, timing, and distribution of penetrative strain during deformation. Eight simple models, each with a geometrically and mechanically similar starting configuration, within the limits of sandbox models, were shortened to different amounts. Model results indicate first that penetrative strain increases with depth in any given model, and second that the proportion of the total shortening accommodated by penetrative strain varies with time. As the deforming wedge approaches stability, penetrative strain is highest just before initiation of a new thrust fault, after which the penetrative strain component abruptly decreases. Each model also contains a foreland zone of penetrative strain, in which penetrative strain decreases exponentially away from the deformation front. These results are consistent with available field data. Restoration of a seismic-scale cross section indicates that model results can be used to predict the amount of penetrative strain and thus the true total shortening across a deformed region. Estimates of this type may be made for additional cross sections and may provide answers to the problem of “missing shortening” across orogens and the total amount of shortening experienced at collisional plate margins

Sheeting joints and polygonal patterns in the Navajo Sandstone, southern Utah: Controlled by rock fabric, tectonic joints, buckling, and gullying

Sheeting joints are ubiquitous in outcrops of the Navajo Sandstone on the west-central Colorado Plateau, USA. As in granitic terrains, these are opening- mode fractures and form parallel to land surfaces. In our study areas in south-central Utah, liquefaction during Jurassic seismic events destroyed stratification in large volumes of eolian sediment, and first-order sheeting joints are now preferentially forming in these structureless (isotropic) sandstones. Vertical cross-joints abut the land-surface-parallel sheeting joints, segmenting broad (tens of meters) rock sheets into equant, polygonal slabs ~5 m wide and 0.25 m thick. On steeper slopes, exposed polygonal slabs have domed surfaces; eroded slabs reveal an onion-like internal structure formed by 5-m-wide, second-order sheeting joints that terminate against the crossjoints, and may themselves be broken into polygons. In many structureless sandstone bodies, however, the lateral extent of first-order sheeting joints is severely limited by pre-existing, vertical tectonic joints. In this scenario, non-conjoined sheeting joints form extensive agglomerations of laterally contiguous, polygonal domes 3–6 m wide, exposing exhumed sheeting joints. These laterally confined sheeting joints are, in turn, segmented by short vertical cross-joints into numerous small (~0.5 m) polygonal rock masses. We hypothesize that the sheeting joints in the Navajo Sandstone form via contemporaneous, land-surface-parallel compressive stresses, and that vertical cross-joints that delineate polygonal masses (both large and small) form during compression-driven buckling of thin, convex-up rock slabs. Abrasion of friable sandstone during runoff events widens vertical tectonic joints into gullies, enhancing land-surface convexity. Polygonal rock slabs described here provide a potential model for interpretation of similar-appearing patterns developed on the surface of Mars

Energy Assessment Technique for Retrofit Mine-water District Heat Network

UK buildings and energy infrastructures are heavily dependent on natural gas, a large proportion of which is used for space heating. Much of the UKs' gas is imported, therefore a wholesale shift in energy provision is required in order to meet government targets for reducing carbon emissions and improving energy security, without impacting on thermal comfort levels, convenience or cost of supply to the end user. Heat pumps are a potential alternative for modern well insulated homes, however this is not necessarily true of a large proportion of British housing stock which was built prior to 1919. Increasing energy efficiency of older properties remains a significant challenge, which cannot be achieved through insulation and air-tightness interventions alone. This paper investigates the energy demand of pre-1919 dwellings using a holistic surveying approach to provide a more accurate assessment of total household heat demand, and reports on the analysis of eight properties. This information is used to assess the feasibility of using water from disused mine workings to supply a heat pump based, district heat network. The use of renewable solar energy generation and storage technologies, to reduce the heat load and offset increased electricity demand, are also considered

Accommodation of penetrative strain during deformation above a ductile décollement

The accommodation of shortening by penetrative strain is widely considered as an important process during contraction, but the distribution and magnitude of penetrative strain in a contractional system with a ductile décollement are not well understood. Penetrative strain constitutes the proportion of the total shortening across an orogen that is not accommodated by the development of macroscale structures, such as folds and thrusts. In order to create a framework for understanding penetrative strain in a brittle system above a ductile décollement, eight analog models, each with the same initial configuration, were shortened to different amounts in a deformation apparatus. Models consisted of a silicon polymer base layer overlain by three fine-grained sand layers. A grid was imprinted on the surface to track penetra- tive strain during shortening. As the model was shortened, a series of box fold structures developed, with a zone of penetrative strain in the foreland. Penetrative strain in the foreland decreases away from the fold belt. Restoration of the model layers to the horizontal indicates that penetrative strain accounts for 90.5%-30.8% of total shortening in a brittle system with a ductile décollement, compared to 45.2%–3.6% within a totally brittle system. Analog model geometries were consistent with the deformation styles observed in salt-floored systems, such as the Swiss Jura. Penetrative strain has not been accounted for in previous studies of salt-floored regions and estimates of this type could help resolve concerns of missing shortening highlighted by global positioning system data

The influence of the Great Falls Tectonic Zone on the thrust sheet geometry of the southern Sawtooth Range, Montana, USA

The reactivation potential of pre-existing deep-seated structures influences deformation structures produced in subsequent compression. This contribution investigates thrust geometries produced in surface thrust sheets of the Sawtooth Range, Montana, USA, deforming over a previously faulted sedimentary section. Surface thrust fault patterns were picked using existing maps and remote sensing. Thrust location and regional transport direction was also verified in the field. These observations were used to design a series of analogue models, involving deformation of a brittle cover sequence over a lower section with varying numbers of vertical faults. A final model tested the effect of decoupling the upper cover and lower section with a ductile detachment, in a scenario closer to that of the Sawtooth Range. Results demonstrate that complexity in surface thrust sheets can be related to heterogeneity within the lower sedimentary section, even when there is a detachment between this section and the rest of the cover. This complexity is best observed in the map view, as the models do not show the deep-seated faults propagating into the cover. These results were then used to predict specific locations of discrete basement fault strands in the study area, associated with what is generally mapped as the Scapegoat-Bannatyne Trend. The deep-seated faults are more likely to be reactivated as strike-slip features in nature, given the small obliquity between the ENE-directed compression direction and the NE-oriented basement faults. More generally, these results can be used to govern evaluation of thrust belts deforming over faulted basement, and to predict the locations of specific fault strands in a region where this information is unknow

Daylighting: appraisal at the early design stages

For a building design team concerned with the quality of the internal environment of buildings the percentage area of glazing on a building facade is one of the most useful criteria for judging the building envelope as a modifier of climate at early design stages since it is at the window that the various environmental parameters (heat, light and sound) remain only minimally modified. The percentage area of glazing can be used to relate the numerous and often conflicting functions of the window such as the provision of daylight, summer time teperatures, sound insulation, energy efficiency and view satisfaction

Post-Mississippian tectonic evolution of the Nemaha Tectonic Zone and Midcontinent Rift System, SE Nebraska and N Kansas

The geologic structures of the central Midcontinent of the USA are largely buried and known only from geophysical datasets, coupled with sparse well control and limited outcrop. Such unconstrained geophysical models preclude a deeper assessment of possible continental interior seismic hazards, which have the potential to cause appreciable damage. Within the study area in southeastern Nebraska and northeastern Kansas is an area of elevated seismic risk, with a spatial relationship to the Nemaha Tectonic Zone and the Midcontinent Rift System. Using sequential restorations of three published cross sections within Nebraska and Kansas this study demonstrates that the Nemaha Tectonic Zone and Midcontinent Rift System have each been reactivated several times since the end of the Mississippian (the details of deformation prior to the Mississippian are not considered). Our reconstructions indicate that in addition to major Pennsylvanian-Early Permian fault reactivation during the Ancestral Rocky Mountain orogeny there was also deformation both prior to the post-Mississippian unconformity associated with uplift on the Nemaha Tectonic Zone and after the deposition of late Early-early Late Cretaceous sediments in the study area, potentially due to the Laramide orogeny. Results also indicate that the magnitude of the far-field stresses is sufficient to cause seismogenic reactivation on favorably oriented pre-existing faults. This history of reactivation of geologic structures in the central Midcontinent suggests that seismic hazards in the region in the present cannot be ruled out. Though dangerous large earthquakes are uncommon in the continental interior, seismic activity along the structures in the study area would threaten several large population centers and the potential for this activity should not be ignored

Post-Mississippian tectonic evolution of the Nemaha Tectonic Zone and Midcontinent Rift System, SE Nebraska and N Kansas

The geologic structures of the central Midcontinent of the USA are largely buried and known only from geophysical datasets, coupled with sparse well control and limited outcrop. Such unconstrained geophysical models preclude a deeper assessment of possible continental interior seismic hazards, which have the potential to cause appreciable damage. Within the study area in southeastern Nebraska and northeastern Kansas is an area of elevated seismic risk, with a spatial relationship to the Nemaha Tectonic Zone and the Midcontinent Rift System. Using sequential restorations of three published cross sections within Nebraska and Kansas this study demonstrates that the Nemaha Tectonic Zone and Midcontinent Rift System have each been reactivated several times since the end of the Mississippian (the details of deformation prior to the Mississippian are not considered). Our reconstructions indicate that in addition to major Pennsylvanian-Early Permian fault reactivation during the Ancestral Rocky Mountain orogeny there was also deformation both prior to the post-Mississippian unconformity associated with uplift on the Nemaha Tectonic Zone and after the deposition of late Early-early Late Cretaceous sediments in the study area, potentially due to the Laramide orogeny. Results also indicate that the magnitude of the far-field stresses is sufficient to cause seismogenic reactivation on favorably oriented pre-existing faults. This history of reactivation of geologic structures in the central Midcontinent suggests that seismic hazards in the region in the present cannot be ruled out. Though dangerous large earthquakes are uncommon in the continental interior, seismic activity along the structures in the study area would threaten several large population centers and the potential for this activity should not be ignored