This paper presents an analysis of the zero-carbon performance of a case-study building which is representative of a growing number of new buildings that are being built on redevelopment sites in ...inner-city areas in the UK. Compact urban dwellings are apartment style buildings with a floor area of ∼50 m
2
per dwelling, often based over two floors. The constraints of this type of building on achieving zero-carbon performance in the context of the Code for Sustainable Homes is discussed and the shortcomings of the code are demonstrated in terms of the target heat and electricity demand targets for the design of the building systems. A graphical representation of the simulation results is used to present the findings. It has been demonstrated that in specific urban contexts, zero-carbon performance as defined within the current UK compliance framework may be very difficult to achieve in practice given the assumptions used in the simulation here. Therefore, it is very likely that zero-carbon compact urban dwellings may require a net off-site import of electrical and/or thermal energy.
•Strength of 3D-printed concrete containing cracks/defects is investigated experimentally.•3D-printed concrete is modelled as a linear-elastic, homogenous, and isotropic material.•Critical distance ...methods are used to assess static strength of 3D-printed concrete.•The proposed assessment methods can be used in conjunction with commercial FE codes.
The present paper deals with the use of the Theory of Critical Distances to model the detrimental effect of cracks and manufacturing defects in 3D-printed concrete subjected to static loading. The robustness of the proposed approach was assessed against a number of experimental results that were generated by testing, under three-point bending, 3D-printed rectangular section specimens weakened by saw-cut crack-like sharp notches, surface roughness (due to the extrusion filaments) and manufacturing defects. The sound agreement between experiments and predictive model allowed us to demonstrate that the Theory of Critical Distances is not only a reliable design approach, but also a powerful tool suitable for guiding and informing effectively the additive manufacturing process.
Organic solvent nanofiltration (OSN) technology is a membrane process for molecular separation in harsh organic media. However, despite having well-documented potential applications, development ...hurdles have hindered the widespread uptake of OSN technology. One of the most promising areas of application is as an iterative synthesis platform, for instance for oligonucleotides or peptides, where a thorough purification step is required after each synthesis cycle, preferably in the same working solvent. In this work, we report a process development study for liquid-phase oligonucleotide synthesis (LPOS) using OSN technology. Oligonucleotide (oligo) based drugs are being advanced as a new generation of therapeutics functioning at the protein expression level. Currently, over 100 oligo based drugs are undergoing clinical trials, suggesting that it will soon be necessary to produce oligos at a scale of metric tons per year. However, there are as yet no synthesis platforms that can manufacture oligos at >10 kg batch scale. With the process developed here, we have successfully carried out eight iterative cycles of chain extension and synthesized 5-mer and 9-mer 2′-O-methyl oligoribonucleotide phosphorothioates, all in liquid phase media. This paper discusses the key challenges, both anticipated and unexpected, faced during development of this process and suggests solutions to reduce the development period. An economic analysis has been carried out, highlighting the potential competitiveness of the LPOS-OSN process and the necessity for a solvent recovery unit.
The origins of good and evil and the problem of theodicy present a special set of challenges in Buddhism, which is relatively less concerned with consideration of first causes than are monotheistic ...religions. Buddhism focuses less on the issue of why evil and its incumbent suffering are present in the world and more on the question of how to respond to that evil. This emphasis on soteriology over metaphysics is seen in the characteristic invocation of pragmatic criteria for the evaluation of doctrines and practices; the recurrent motif of the Buddha as therapist rather than theorist; and the pervasive influence of the meta-theory of upāya (expedients or stratagems). This article will examine the soteriological dimension of the broader Buddhist response to evil and explore some of the explicit examinations of the problem of a Buddhist “theodicy” in later Mahāyāna monistic ontologies, which are explored in Korean Buddhist materials: viz., if the mind is innately enlightened or inherently pure, whence do ignorance or defilements arise?
The ability to specifically attach chemical probes to individual proteins represents a powerful approach to the study and manipulation of protein function in living cells. It provides a simple, ...robust and versatile approach to the imaging of fusion proteins in a wide range of experimental settings. However, a potential drawback of detection using chemical probes is the fluorescence background from unreacted or nonspecifically bound probes. In this report we present the design and application of novel fluorogenic probes for labeling SNAP‐tag fusion proteins in living cells. SNAP‐tag is an engineered variant of the human repair protein O6‐alkylguanine‐DNA alkyltransferase (hAGT) that covalently reacts with benzylguanine derivatives. Reporter groups attached to the benzyl moiety become covalently attached to the SNAP tag while the guanine acts as a leaving group. Incorporation of a quencher on the guanine group ensures that the benzylguanine probe becomes highly fluorescent only upon labeling of the SNAP‐tag protein. We describe the use of intramolecularly quenched probes for wash‐free labeling of cell surface‐localized epidermal growth factor receptor (EGFR) fused to SNAP‐tag and for direct quantification of SNAP‐tagged β‐tubulin in cell lysates. In addition, we have characterized a fast‐labeling variant of SNAP‐tag, termed SNAPf, which displays up to a tenfold increase in its reactivity towards benzylguanine substrates. The presented data demonstrate that the combination of SNAPf and the fluorogenic substrates greatly reduces the background fluorescence for labeling and imaging applications. This approach enables highly sensitive spatiotemporal investigation of protein dynamics in living cells.
A cleaner image: We report the design and application of an improved labeling system, which combines the use of a faster reacting variant of SNAP‐tag, termed SNAPf, with fluorogenic benzylguanine probes for wash‐free labeling of fusion proteins in living cells.
Due to the discovery of RNAi, oligonucleotides (oligos) have re‐emerged as a major pharmaceutical target that may soon be required in ton quantities. However, it is questionable whether solid‐phase ...oligo synthesis (SPOS) methods can provide a scalable synthesis. Liquid‐phase oligo synthesis (LPOS) is intrinsically scalable and amenable to standard industrial batch synthesis techniques. However, most reported LPOS strategies rely upon at least one precipitation per chain extension cycle to separate the growing oligonucleotide from reaction debris. Precipitation can be difficult to develop and control on an industrial scale and, because many precipitations would be required to prepare a therapeutic oligonucleotide, we contend that this approach is not viable for large‐scale industrial preparation. We are developing an LPOS synthetic strategy for 2′‐methyl RNA phosphorothioate that is more amenable to standard batch production techniques, using organic solvent nanofiltration (OSN) as the critical scalable separation technology. We report the first LPOS‐OSN preparation of a 2′‐Me RNA phosphorothioate 9‐mer, using commercial phosphoramidite monomers, and monitoring all reactions by HPLC, 31P NMR spectroscopy and MS.
Oligonucleotides are major pharmaceutical targets, but solid‐phase methods struggle to provide a scalable synthesis. A liquid‐phase oligonucleotide synthesis (LPOS) synthetic strategy has been developed that is more amenable to standard batch production techniques, using organic‐solvent nanofiltration (OSN, see scheme) as the critical scalable separation technology. The LPOS‐OSN preparation of a 2′‐Me RNA phosphorothioate 9‐mer is reported.
An approach to identification of evolving fuzzy rule-based (eR) models is proposed. eR models implement a method for the noniterative update of both the rule-base structure and parameters by ...incremental unsupervised learning. The rule-base evolves by adding more informative rules than those that previously formed the model. In addition, existing rules can be replaced with new rules based on ranking using the informative potential of the data. In this way, the rule-base structure is inherited and updated when new informative data become available, rather than being completely retrained. The adaptive nature of these evolving rule-based models, in combination with the highly transparent and compact form of fuzzy rules, makes them a promising candidate for modeling and control of complex processes, competitive to neural networks. The approach has been tested on a benchmark problem and on an air-conditioning component modeling application using data from an installation serving a real building. The results illustrate the viability and efficiency of the approach.
Model-based techniques for automated condition monitoring of HVAC systems have been under development for some years. The generation of false alarms has been identified as a principal factor ...affecting the potential usefulness of condition monitoring in HVAC applications. Results from the application of these methods to systems installed in real buildings have highlighted the difficulty in selecting good alarm thresholds that balance robustness (lack of false alarms) and sensitivity (early detection). This paper demonstrates that this balance can be met in a transparent and analytical manner, through the application of uncertainty analysis. The paper discusses the sources of uncertainty associated with component models and system measurements. A condition monitoring scheme applied to a typical HVAC cooling coil subsystem installed in a real building is presented. Faults are artificially introduced into the system and are used in conjunction with fault-free operation to demonstrate the sensitivity and robustness of the scheme. The principle conclusions drawn by the paper consider the likely minimum magnitudes of faults that can be detected in typical HVAC systems, without false alarm generation. More broadly however, the paper demonstrates that the issue of uncertainty affects all aspects of system monitoring, modelling and control.
Antimicrobial resistance is a growing global health issue. It is also a recognised problem in veterinary medicine. Between September and December 2015 the authors administered a cross-sectional ...survey to licensed veterinarians in Washington State to assess factors affecting antimicrobial prescribing practices among veterinarians in Washington State. Two hundred and three veterinarians completed the survey. The majority of respondents (166, 82 per cent) were engaged in small animal or exotic animal practice. 24 per cent of respondents reported not ordering culture and sensitivity (C/S) testing in practice. Of the 76 per cent of veterinarians who reported ordering C/S tests, 36 per cent reported ordering such testing 'often' or 'always' when treating presumptive bacterial infections. Most respondents (65 per cent) mentioned cost as the most common barrier to ordering a C/S test. Only 16 (10 per cent) respondents reported having access to or utilising a clinic-specific antibiogram. This survey demonstrated that while antimicrobials are commonly used in veterinary practice, and veterinarians are concerned about antimicrobial resistance, cost is a barrier to obtaining C/S tests to guide antimicrobial therapy. Summaries of antimicrobial resistance patterns are rarely available to the practising veterinarian. Efforts to promote antimicrobial stewardship in a 'One Health' manner should address barriers to the judicious use of antimicrobials in the veterinary practice setting.
PDF
