83 research outputs found
Handling uncertainties in modelling manufacturing processes with hybrid swarm intelligence
Seldom has research regarding manufacturing process modelling considered the two common types ofuncertainties which are caused by randomness as in material properties and by fuzziness as in the inexact knowledge in manufacturing processes. Accuracies of process models can be downgraded if these uncertainties are ignored in the development of process models. In this paper, a hybrid swarm intelligence algorithm for developing process models which intends to achieve significant accuracies for manufacturing process modelling by addressing these two uncertainties is proposed. The hybrid swarm intelligence algorithm first applies the mechanism of particle swarm optimisation to generate structures of process models in polynomial forms, and then it applies the mechanism of fuzzy least square regression algorithm to determine fuzzy coefficients on polynomials so as to address the two uncertainties, fuzziness and randomness. Apart from addressing the two uncertainties, the common feature in manufacturing processes, nonlinearities between process parameters, which are not inevitable in manufacturing processes, can also be addressed. The effectiveness of the hybrid swarm algorithm is demonstrated by modelling of the solder paste dispensing process
Moving teaching online: cultural barriers experienced by university teachers during Covid19
This empirical study examines the experiences of academics and professional service staff in a large UK university during first weeks of the transition to online teaching and working from home during the Covid-19 pandemic. The method draws on the work by Gourlay and Oliver (2018) to explore engagement with the digital university in everyday practice. Using data from 412 survey responses and 32 interviews, the study traces varying ways staff characterised themselves during the first months of lockdown in the UK (from March to July, 2020). The findings highlight that university support services underwent a metamorphosis to support the transition to online teaching. However, insufficient attention was paid to the ‘identity crisis’ and threats perceived by academics who were used to teaching students on campus. Academics tended to focus on transferring traditional teaching practices to the online environment, rather than on changing teaching practice, leaving face-to-face teaching as the default point of reference. These cultural barriers are a persistent obstacle to a more productive engagement with digitalisation. Transitioning to online teaching involves continuing existing work while also learning new practices. Such efforts were challenging for teaching staff who did not have dedicated space at home to work and those with caring responsibilities. This, combined with gendered patterns around caring and the extra support needed by students during the crisis, added emotional labour to already-full workloads. We recommend that intersecting forms of disadvantage be acknowledged, supported and rewarded for universities to create sustainable and just futures
Privileged Structure: Novel Indane Scaffolds as Potential Anticancer and Anti-Inflammatory Agents
The identification and use of “privileged structures” can increase the reliability and shorten the process in the drug discovery and drug design (a-b). Indane scaffolds occur in various natural products and they constitute the privileged structure that is ubiquitous in many biologically and pharmaceutically active molecules (c-e). Our research group has been working on the synthesis and pharmacological activity of nature identical and synthetically modified indanes and indanones for 20 years. In the current study, the molecular design is centred on elaboration of a fern derived bioactive pharmacophore. The fern is used in traditional Taiwanese medicine to treat inflammation, allergy, stomach cramps and fever (f). Using a synthetic approach we have designed a novel chemical scaffold which can be modified to inhibit angiogenesis and 5-lipoxygenase activity. The parent scaffold and a number of strategically modified derivatives were initially screened using the Zebra fish (Danio rerio) model of tumour angiogenesis (g). This screen led to the identification of two lead molecules, which were then further evaluated in in vitro cell lines and colorectal explants. Results from these experiments establish that the lead compounds affect inter-segmental vessel formation. These molecules also inhibit cell invasion and tube formation. When evaluated in ex vivo colorectal cancer explants where the molecules significantly affected angiogenic and inflammatory protein secretions. These small molecules also alter gene expression. Modification of the scaffold can inhibit 5-lipoxygenase activity. These data suggest that the new scaffold may have significant potential in the treatment of angiogenesis and inflammatory related diseases
Polynomial modeling for time-varying systems based on a particle swarm optimization algorithm
In this paper, an effective particle swarm optimization (PSO) is proposed for polynomial models for time varying systems. The basic operations of the proposed PSO are similar to those of the classical PSO except that elements of particles represent arithmetic operations and variables of time-varying models. The performance of the proposed PSO is evaluated by polynomial modeling based on various sets of time-invariant and time-varying data. Results of polynomial modeling in time-varying systems show that the proposed PSO outperforms commonly used modeling methods which have been developed for solving dynamic optimization problems including genetic programming (GP) and dynamic GP. An analysis of the diversity of individuals of populations in the proposed PSO and GP reveals why the proposed PSO obtains better results than those obtained by GP
The cysteine protease dipeptidyl aminopeptidase 3 does not contribute to egress of Plasmodium falciparum from host red blood cells
The ability of Plasmodium parasites to egress from their host red blood cell is critical for the amplification of these parasites in the blood. Previous forward chemical genetic approaches have implicated the subtilisin-like protease (SUB1) and the cysteine protease dipeptidyl aminopeptidase 3 (DPAP3) as key players in egress, with the final step of SUB1 maturation thought to be due to the activity of DPAP3. In this study, we have utilized a reverse genetics approach to engineer transgenic Plasmodium falciparum parasites in which dpap3 expression can be conditionally regulated using the glmS ribozyme based RNA-degrading system. We show that DPAP3, which is expressed in schizont stages and merozoites and localizes to organelles distinct from the micronemes, rhoptries and dense granules, is not required for the trafficking of apical proteins or processing of SUB1 substrates, nor for parasite maturation and egress from red blood cells. Thus, our findings argue against a role for DPAP3 in parasite egress and indicate that the phenotypes observed with DPAP3 inhibitors are due to off-target effects
The depression impairment scale for parents (DISP): a new scale for the measurement of impairment in depressed parents
Children of depressed parents are at increased risk of developing mood disorders but mechanisms of intrafamilial transmission are currently unclear. One rarely investigated area is the impact of depression on a parent's everyday functioning. Currently there are no validated assessments of depression-specific parental impairment. The creation of such a measure would complement depression symptom counts, providing a more comprehensive account of the parent's depression. We therefore aimed to develop a valid and reliable measure of impairment specifically associated with parental depression. In a longitudinal study of parents with recurrent unipolar depression and their offspring, we collected data from 337 parents. These participants completed the Depression Impairment Scale for Parents (DISP), a questionnaire assessing depression-associated impairment in multiple domains of functioning. Factor analysis revealed that this measure consisted of two factors - impairment in routine tasks/activities and impairment in family functioning - that together accounted for 51.04% of variance. The scale evidenced good internal consistency (Cronbach's alpha=0.82). The DISP also displayed good construct and criterion validity as evidenced by significant associations with established measures of depression severity and global impairment. These results demonstrate that the DISP is a valid and reliable measure of depression-associated impairment in parents. © 2013 Elsevier Ireland Ltd
Sudden cardiac death due to deficiency of the mitochondrial inorganic pyrophosphatase PPA2
We have used whole exome sequencing to identify biallelic missense mutations in the nuclearencoded
mitochondrial inorganic pyrophosphatase (PPA2) in ten individuals from four unrelated
pedigrees that are associated with mitochondrial disease. These individuals show a range of severity,
indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe
symptoms include seizures, lactic acidosis and cardiac arrhythmia and death within days of birth. In
the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite
sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life.
Comparison of normal and mutated PPA2 containing mitochondria from fibroblasts showed the
activity of inorganic pyrophosphatase significantly reduced in affected individuals. Recombinant
PPA2 enzymes modeling hypomorphic missense mutations had decreased activity that correlated
with disease severity. These findings confirm the pathogenicity of PPA2 mutations, and suggest that
PPA2 is a new cardiomyopathy-associated protein, which has a greater physiological importance in
mitochondrial function than previously recognized
Robust estimation of bacterial cell count from optical density
Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
Delayed death by plastid inhibition in Plasmodium falciparum
© 2019 Kit KennedyApicomplexan parasites possess a plastid organelle called the apicoplast. Inhibitors that selectively target apicoplast housekeeping functions, including DNA replication and protein translation, are lethal for the parasite, and several (doxycycline, clindamycin, and azithromycin) are in clinical use as antimalarials. A major limitation of such drugs is that treated parasites only arrest one intraerythrocytic development cycle (approximately 48 hours) after treatment commences, a phenotype known as the ‘delayed death’ effect. The molecular basis of delayed death is a long-standing mystery in parasitology and establishing the mechanism would aid rational clinical implementation of apicoplast-targeted drugs. Parasites undergoing delayed death transmit defective apicoplasts to their daughter cells and cannot produce the sole, blood-stage essential metabolic product of the apicoplast: the isoprenoid precursor isopentenyl pyrophosphate. How the isoprenoid precursor depletion kills the parasite remains unknown. We investigated the requirements for the range of isoprenoids in the human malaria parasite Plasmodium falciparum and characterised the molecular and morphological phenotype of parasites experiencing delayed death.
Metabolomic profiling reveals disruption of digestive vacuole function in the absence of apicoplast derived isoprenoids. Three-dimensional electron microscopy reveals digestive vacuole fragmentation and the accumulation of cytostomal invaginations, characteristics common in digestive vacuole disruption. We show that DV disruption results from a defect in the trafficking of vesicles to the digestive vacuole. The loss of prenylation of vesicular trafficking proteins abrogates their membrane attachment and function and prevents the parasite from feeding. Our data show that the proximate cause of delayed death is an interruption of protein prenylation and consequent cellular trafficking defects
Forever fissiparous: asexual propagation and stable demography in a tropical and geographically isolated asterinid sea star
Sea stars of the family Asterinidae are well known for their diverse life history strategies encompassing sexual reproduction through various larval forms, while others, all multi-armed species, through clonal asexual reproduction. For at least 25\ua0years, a geographically isolated population of the minute (radius < 7\ua0mm) tropical Pacific fissiparous asterinid, Ailsastra heteractis, has been locally abundant in a shallow water coral rubble habitat at One Tree Island, southern Great Barrier Reef. The population biology of this sea star was investigated over 14\ua0years to characterise its asexual reproduction through fission (splitting in half) and to determine whether a size threshold is reached for an expected switch to sexual reproduction. Fission followed by regeneration was the dominant propagation mechanism generating individuals that varied in arm number (2–7) and length (0.5–6.9\ua0mm). Recently split individuals were present year round with regenerating individuals being the most prevalent body form. Growth rates and fission activity, as measured by mean arm length, varied among months but with no overall pattern. Analyses of arm length data based on season indicated that fission activity was lowest in autumn. There was a positive correlation between the incidence of fission and air and water temperature with a decrease in the proportion of recently split individuals in winter and an increase in summer. Fission was present in all size classes with no evidence of a switch to a larger sexual morphotype with growth. Juvenile recruitment from sexual reproduction was not evident. Extensive searches did not reveal the presence of other populations of A. heteractis. The absence of recruitment and reproductive organs coupled with a stable population demography indicates that propagation by fission is the only reproductive mechanism for the A. heteractis population
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