Abstract
Reuse of building components is one of the recommended circular strategies to reduce the environmental impact of new buildings. However, reclaimed building components are more difficult to ...design with than new products. While new products can be made to match exact needs, the salvaged components have predefined dimensions and quality limitations. Following the Design Science Research methodology, we attempt to answer how the reuse design can be aided by a digital design tool. The developed matching algorithms suggest the optimal assignment of available elements for the desired configuration, considering user-defined constraints and optimisation criteria. In the test cases, we seek to optimise the global warming potential of timber framing elements, defined by life cycle assessment, though the tool is not limited to this objective. The implementation includes greedy algorithms, bipartite graphs, and mixed integer linear programming. The usefulness of the proposed solution is evaluated on simulated sets of building elements in terms of embodied emission reduction and speed of the calculation. The paper contributes with methodologies, algorithms, and test cases to assess their performance. Practitioners can apply the proposed solution to reduce the time of designing with salvaged materials, which can lead to the popularisation of the circular design.
Posttranslational modification with ubiquitin chains controls cell fate in all eukaryotes. Depending on the connectivity between subunits, different ubiquitin chain types trigger distinct outputs, as ...seen with K48- and K63-linked conjugates that drive protein degradation or complex assembly, respectively. Recent biochemical analyses also suggested roles for mixed or branched ubiquitin chains, yet without a method to monitor endogenous conjugates, the physiological significance of heterotypic polymers remained poorly understood. Here, we engineered a bispecific antibody to detect K11/K48-linked chains and identified mitotic regulators, misfolded nascent polypeptides, and pathological Huntingtin variants as their endogenous substrates. We show that K11/K48-linked chains are synthesized and processed by essential ubiquitin ligases and effectors that are mutated across neurodegenerative diseases; accordingly, these conjugates promote rapid proteasomal clearance of aggregation-prone proteins. By revealing key roles of K11/K48-linked chains in cell-cycle and quality control, we establish heterotypic ubiquitin conjugates as important carriers of biological information.
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•K11/K48-bispecific antibodies detect endogenous K11/K48-linked ubiquitin chains•K11/K48-branched chains modify mitotic regulators and misfolded nascent proteins•K11/K48-dependent proteasomal degradation prevents protein aggregation•Mutations in K11/K48-specific enzymes are found in neurodegenerative diseases
Bispecific antibodies reveal the presence and function of heterotypic ubiquitin chains containing K11 and K48 linkages in cell-cycle regulation and protein quality control.
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•ARC reactor designed to have 500MW fusion power at 3.3m major radius.•Compact, simplified design allowed by high magnetic fields and jointed magnets.•ARC has innovative plasma ...physics solutions such as inboardside RF launch.•High temperature superconductors allow high magnetic fields and jointed magnets.•Liquid immersion blanket and jointed magnets greatly simplify tokamak reactor design.
The affordable, robust, compact (ARC) reactor is the product of a conceptual design study aimed at reducing the size, cost, and complexity of a combined fusion nuclear science facility (FNSF) and demonstration fusion Pilot power plant. ARC is a ∼200–250MWe tokamak reactor with a major radius of 3.3m, a minor radius of 1.1m, and an on-axis magnetic field of 9.2T. ARC has rare earth barium copper oxide (REBCO) superconducting toroidal field coils, which have joints to enable disassembly. This allows the vacuum vessel to be replaced quickly, mitigating first wall survivability concerns, and permits a single device to test many vacuum vessel designs and divertor materials. The design point has a plasma fusion gain of Qp≈13.6, yet is fully non-inductive, with a modest bootstrap fraction of only ∼63%. Thus ARC offers a high power gain with relatively large external control of the current profile. This highly attractive combination is enabled by the ∼23T peak field on coil achievable with newly available REBCO superconductor technology. External current drive is provided by two innovative inboard RF launchers using 25MW of lower hybrid and 13.6MW of ion cyclotron fast wave power. The resulting efficient current drive provides a robust, steady state core plasma far from disruptive limits. ARC uses an all-liquid blanket, consisting of low pressure, slowly flowing fluorine lithium beryllium (FLiBe) molten salt. The liquid blanket is low-risk technology and provides effective neutron moderation and shielding, excellent heat removal, and a tritium breeding ratio≥1.1. The large temperature range over which FLiBe is liquid permits an output blanket temperature of 900K, single phase fluid cooling, and a high efficiency helium Brayton cycle, which allows for net electricity generation when operating ARC as a Pilot power plant.
All eukaryotes require intricate protein networks to translate developmental signals into accurate cell fate decisions. Mutations that disturb interactions between network components often result in ...disease, but how the composition and dynamics of complex networks are established remains poorly understood. Here, we identify the E3 ligase UBR5 as a signaling hub that helps degrade unpaired subunits of multiple transcriptional regulators that act within a network centered on the c-Myc oncoprotein. Biochemical and structural analyses show that UBR5 binds motifs that only become available upon complex dissociation. By rapidly turning over unpaired transcription factor subunits, UBR5 establishes dynamic interactions between transcriptional regulators that allow cells to effectively execute gene expression while remaining receptive to environmental signals. We conclude that orphan quality control plays an essential role in establishing dynamic protein networks, which may explain the conserved need for protein degradation during transcription and offers opportunities to modulate gene expression in disease.
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•The E3 ligase UBR5 targets many transcription factors that cooperate with c-Myc•UBR5 selectively recognizes unpaired transcription factor subunits•Substrate sandwiching by tetrameric UBR5 establishes specificity for unpaired subunits•Orphan degradation establishes dynamic interaction networks driving gene expression
Cells use orphan quality control to constantly degrade unpaired transcription factor subunits and, thereby, establish dynamic protein interaction networks that drive accurate gene expression and cell fate determination.
As we strive to improve efficiency and minimise environmental impact in the construction industry, it is important to consider how these objectives impact the work and productivity of designers. This ...article presents a tool to assist designers in matching reclaimed building products with design intent. The demonstration is based on an actual design project of a two-storey public building made of reclaimed timber from disassembled barns. The algorithm’s objective is to propose optimal matching in terms of a structure’s environmental impact without overloading the user with additional work or excess information. The impact includes emissions embodied in material and related to the transportation from the donor site. The algorithm is integrated into the Grasshopper interface for easier use. All the inputs and objectives are quantitative and fully customisable. The user can still assess qualitative characteristics thanks to a graphical representation of the result. The demonstration shows how automation can simplify the design process with reclaimed elements, support traditional design workflows and enable improvements towards a more sustainable construction industry.
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•Dynamic positioning opens deep waters with fewer spatial disputes to offshore wind.•Prior work has not analyzed the cost of this application, as done in this ...analysis.•Intermediate-size turbines achieve lower cost of energy than the largest.•910 km of mooring chains and their environmental impacts can be eliminated.•3 megawatt-hours of stored energy may be needed to maintain position in low winds.
In addition to technical and economic challenges, the offshore wind industry must also contend with environmental and socio-political concerns that constrain development. Here, the viability of dynamically positioned floating offshore wind platforms that could ameliorate these constraints is analyzed. Such a design can unlock deeper, less-contentious waters that are farther from shore and reduce environmental interactions in the ocean, thus expanding and improving deployment opportunities. While prior studies on this application only focused on energy performance, the resulting cost of energy and benefits have not yet been quantified. Although prior studies found that the energy-performance of this strategy does not show promise, it is possible that a full understanding of the costs and benefits will reveal a decision space where it makes sense. To address this gap in the literature, the cost penalty of this application compared to moored turbines is estimated here. A physical engineering model is used to compute the environmental loads on a floating offshore wind turbine to estimate the expected energy needed by the station-keeping thrusters and one potential environmental benefit—eliminated mooring chains. The models were validated using marine engineering simulation software. Dynamic positioning realizes a cost penalty of at least 30 U.S. dollars/megawatt-hour while eliminating up to 900 km of mooring chains for a 1-gigawatt array. Up to 3 megawatt-hours of stored energy are needed to station-keep during continuous low winds. Furthermore, dynamic positioning is more viable for turbines of intermediate size (8–10 MW) rather than larger turbines (15 MW). The results show that aerodynamic loads on the turbine fall sharply beyond the rated wind speed, operational and design improvements may further improve the viability of this application, and the energy performance of this application continually improves with added thrusters although the cost of energy does not.
Objective
To delineate the features of a novel neurodegenerative disease.
Methods
We report three children of three related families with congenital microphthalmia and blindness, and progressive ...spasticity, microcephaly, seizures, and profound mental retardation.
Results
A magnetic resonance imaging scan was normal at birth. However, follow‐up studies showed progressive atrophy involving the cerebral white matter and cortex, cerebellum, brainstem, and corpus callosum. The white matter changes extended into the subcortical region leaving only small islands of remaining cortical tissue. Known metabolic conditions involving white matter degeneration were excluded.
Interpretation
We propose this to be a novel autosomal recessive neurodegenerative disorder to be coined MOBA (microphthalmia brain atrophy) disease. Ann Neurol 2006;59:719–723
Background: Mesenchymal stromal/stem cells (MSCs) play a critical role in wound healing. Corlicyte® is an MSC product derived from allogeneic umbilical cord tissue donated under an institutional ...review board-approved protocol and processed in accordance with section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act. This open-label phase 1 trial was performed under a United States Food and Drug Administration Investigational New Drug Application to establish the safety and tolerability of Corlicyte® in patients with diabetes and chronic diabetic foot ulcer (DFU). Methods: Escalating doses were applied topically twice a week for up to 8 weeks after ulcer debridement, wound photography, and measurement. Subjects were followed for 4 weeks after the treatment phase. Adverse events were assessed at every visit. Results: Nine subjects in 2 dosing cohorts completed the trial. No subjects experienced a serious adverse reaction to Corlicyte® or the development of anti-human leukocyte antigen (HLA) antibodies. Sixty percentage of subjects in the lower dose cohort experienced ulcer closure by Day 70 of follow-up, while the mean ulcer size was reduced by 54–67% in the other subjects. Conclusions: Topical administration of Corlicyte®, a novel biologic therapy consisting of allogeneic umbilical cord lining MSCs, appeared safe and tolerable and resulted in a significant decrease in ulcer area, demonstrating its potential as a therapy for healing of chronic DFU.
► A new scaling for obtaining reactor similarity in the divertor of scaled tokamaks. ► Conceptual design for a tokamak (“Vulcan”) to implement this new scaling. ► Demountable superconducting coils ...and compact neutron shielding. ► Helium-cooled high-temperature vacuum vessel and first wall. ► High-field-side lower hybrid current drive for non-inductive operation.
An economically viable magnetic-confinement fusion reactor will require steady-state operation and high areal power density for sufficient energy output, and elevated wall/blanket temperatures for efficient energy conversion. These three requirements frame, and couple to, the challenge of plasma–material interaction (PMI) for fusion energy sciences. Present and planned tokamaks are not designed to simultaneously meet these criteria. A new and expanded set of dimensionless figures of merit for PMI have been developed. The key feature of the scaling is that the power flux across the last closed flux surface P/S≃1MWm−2 is to be held constant, while scaling the core volume-averaged density weakly with major radius, n∼R−2/7. While complete similarity is not possible, this new “P/S” or “PMI” scaling provides similarity for the most critical reactor PMI issues, compatible with sufficient current drive efficiency for non-inductive steady-state core scenarios. A conceptual design is developed for Vulcan, a compact steady-state deuterium main-ion tokamak which implements the P/S scaling rules. A zero-dimensional core analysis is used to determine R=1.2m, with a conventional reactor aspect ratio R/a=4.0, as the minimum feasible size for Vulcan. Scoping studies of innovative fusion technologies to support the Vulcan PMI mission were carried out for three critical areas: a high-temperature, helium-cooled vacuum vessel and divertor design; a demountable superconducting toroidal field magnet system; and a steady-state lower hybrid current drive system utilizing a high-field-side launch position.
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