JURNAL AGROTEKNOLOGI
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Turing conditions for pattern forming systems on evolving manifolds
No full textThe study of pattern-forming instabilities in reaction–diffusion systems on growing or otherwise time-dependent domains arises in a variety of settings, including applications in developmental biology, spatial ecology, and experimental chemistry. Analyzing such instabilities is complicated, as there is a strong dependence of any spatially homogeneous base states on time, and the resulting structure of the linearized perturbations used to determine the onset of instability is inherently non-autonomous. We obtain general conditions for the onset and structure of diffusion driven instabilities in reaction–diffusion systems on domains which evolve in time, in terms of the time-evolution of the Laplace–Beltrami spectrum for the domain and functions which specify the domain evolution. Our results give sufficient conditions for diffusive instabilities phrased in terms of differential inequalities which are both versatile and straightforward to implement, despite the generality of the studied problem. These conditions generalize a large number of results known in the literature, such as the algebraic inequalities commonly used as a sufficient criterion for the Turing instability on static domains, and approximate asymptotic results valid for specific types of growth, or specific domains. We demonstrate our general Turing conditions on a variety of domains with different evolution laws, and in particular show how insight can be gained even when the domain changes rapidly in time, or when the homogeneous state is oscillatory, such as in the case of Turing–Hopf instabilities. Extensions to higher-order spatial systems are also included as a way of demonstrating the generality of the approach
BpOmpW antigen stimulates the necessary protective T-cell responses against melioidosis
No full textMelioidosis is a potentially fatal bacterial disease caused by Burkholderia pseudomallei and is estimated to cause 89,000 deaths per year in endemic areas of Southeast Asia and Northern Australia. People with diabetes mellitus are most at risk of melioidosis, with a 12-fold increased susceptibility for severe disease. Interferon gamma (IFN-γ) responses from CD4 and CD8 T cells, but also from natural killer (NK) and natural killer T (NKT) cells, are necessary to eliminate the pathogen. We previously reported that immunization with B. pseudomallei OmpW (BpOmpW antigen) protected mice from lethal B. pseudomallei challenge for up to 81 days. Elucidating the immune correlates of protection of the protective BpOmpW vaccine is an essential step prior to clinical trials. Thus, we immunized either non-insulin-resistant C57BL/6J mice or an insulin-resistant C57BL/6J mouse model of type 2 diabetes (T2D) with a single dose of BpOmpW. BpOmpW induced strong antibody responses, stimulated effector CD4+ and CD8+ T cells and CD4+ CD25+ Foxp3+ regulatory T cells, and produced higher IFN-γ responses in CD4+, CD8+, NK, and NKT cells in non-insulin-resistant mice. The T-cell responses of insulin-resistant mice to BpOmpW were comparable to those of non-insulin-resistant mice. In addition, as a precursor to its evaluation in human studies, humanized HLA-DR and HLA-DQ (human leukocyte antigen DR and DQ isotypes, respectively) transgenic mice elicited IFN-γ recall responses in an enzyme-linked immune absorbent spot (ELISpot)-based study. Moreover, human donor peripheral blood mononuclear cells (PBMCs) exposed to BpOmpW for 7 days showed T-cell proliferation. Finally, plasma from melioidosis survivors with diabetes recognized our BpOmpW vaccine antigen. Overall, the range of approaches used strongly indicated that BpOmpW elicits the necessary immune responses to combat melioidosis and bring this vaccine closer to clinical trials
Beowulf 501b and the authority of old English poetical manuscripts
No full textIn his Old English grammar, A. Campbell put forward his theory of Old English accentuation, according to which disyllabic words like Bēowulf and ǣniġ receive a half-stress only if made trisyllabic by the addition of an inflection (as in Bēowulfes or ǣniġra), provided the middle syllable is heavy. A. J. Bliss tacitly rejected Campbell’s analysis when he postulated the existence of metrical type 3B2, a rare rhythmical pattern in which trisyllabic forms like Bēowulfes and ǣniġra must exceptionally be assumed to lose their otherwise conventional half-stress. Bliss based his analysis on the evidence afforded by four readings from the text of Beowulf: ll. 501b, 932b, 949b, and 1830b. Even though Bliss expressed reservations about his own analysis, he still preferred it to the alternative possibility of emending these four exceptional verses (a possibility that he did not even consider in his book). Non-metrical arguments in support of the emendation of at least one of these verses (1830b), however, had been advanced well before The metre of Beowulf was first published. Since then, ll. 932b and 949b have also been emended on grounds other than metre. This article offers new linguistic reasons for the emendation of l. 501b, the one remaining reading for which no alternative explanation had yet been proposed. It concludes that Bliss was unnecessarily cautious in his treatment of these four aberrant verses, and that, as Kenneth Sisam memorably stated in 1946, conjectural emendation is, and still remains, a useful tool for the study of Old English poetical manuscripts
Naïve individuals promote collective exploration in homing pigeons
No full textGroup-living animals that rely on stable foraging or migratory routes can develop behavioural traditions to pass route information down to inexperienced individuals. Striking a balance between exploitation of social information and exploration for better alternatives is essential to prevent the spread of maladaptive traditions. We investigated this balance during cumulative route development in the homing pigeon Columba livia. We quantified information transfer within pairs of birds in a transmission-chain experiment and determined how birds with different levels of experience contributed to the exploration–exploitation trade-off. Newly introduced naïve individuals were initially more likely to initiate exploration than experienced birds, but the pair soon settled into a pattern of alternating leadership with both birds contributing equally. Experimental pairs showed an oscillating pattern of exploration over generations that might facilitate the discovery of more efficient routes. Our results introduce a new perspective on the roles of leadership and information pooling in the context of collective learning
Adaptive MIMO-VLC system for high data rate communications
No full textIn this paper, we describe a high-speed indoor MIMO-VLC system that adapts the number of MIMO channels and data rate according to channel conditions at user locations. A transmitter coordination algorithm and a data rate adaptive modulation technique have been investigated. At each user location across the room, the number of MIMO transmission channels is varied (by assigning transmitters into one or several groups and sending the same data stream in each group), and the data rate on each group is separately maximised. The system also employs the angle diversity receiver, zero-forcing MIMO equalisation and decision-feedback equalisation to mitigate spatial crosstalk and temporal interference. The performance of the proposed system is evaluated considering a practical indoor MIMO-VLC setup. For the configuration considered a peak overall data rate of 660 Mbps is achieved, and on average the overall data rate is 120 Mbps higher than a conventional spatial multiplexing approach. This shows the potential of this simple allocation scheme, compared with more complex precoding approaches
Ethnic minorities and COVID-19: examining whether excess risk is mediated through deprivation
No full textBackground
People from South Asian and black minority ethnic groups are disproportionately affected by the COVID-19 pandemic. It is unknown whether deprivation mediates this excess ethnic risk.
Methods
We used UK Biobank with linked COVID-19 outcomes occurring between 16th March 2020 and 24th August 2020. A four-way decomposition mediation analysis was used to model the extent to which the excess risk of testing positive, severe disease and mortality for COVID-19 in South Asian and black individuals, relative to white individuals, would be eliminated if levels of high material deprivation were reduced within the population.
Results
We included 15 044 (53.0% women) South Asian and black and 392 786 (55.2% women) white individuals. There were 151 (1.0%) positive tests, 91 (0.6%) severe cases and 31 (0.2%) deaths due to COVID-19 in South Asian and black individuals compared with 1471 (0.4%), 895 (0.2%) and 313 (0.1%), respectively, in white individuals. Compared with white individuals, the relative risk of testing positive for COVID-19, developing severe disease and COVID-19 mortality in South Asian and black individuals were 2.73 (95% CI: 2.26, 3.19), 2.96 (2.31, 3.61) and 4.04 (2.54, 5.55), respectively. A hypothetical intervention moving the 25% most deprived in the population out of deprivation was modelled to eliminate between 40 and 50% of the excess risk of all COVID-19 outcomes in South Asian and black populations, whereas moving the 50% most deprived out of deprivation would eliminate over 80% of the excess risk of COVID-19 outcomes.
Conclusions
The excess risk of COVID-19 outcomes in South Asian and black communities could be substantially reduced with population level policies targeting material deprivation
Biparental inheritance of mitochondrial DNA revisited
No full textEvidence for a biparental mode of mitochondrial DNA (mtDNA) inheritance has been sparse and remains controversial. Recent studies using a range of complementary techniques do not support paternal transmission of mtDNA and highlight the co-amplification of rare, concatenated nuclear mtDNA segments as a technical artefact that may explain previous observations
Mitochondrial inhibitor atovaquone increases tumor oxygenation and inhibits hypoxic gene expression in patients with non-small cell lung cancer
No full textPurpose: Tumor hypoxia fuels an aggressive tumor phenotype and confers resistance to anticancer treatments. We conducted a clinical trial to determine whether the antimalarial drug atovaquone, a known mitochondrial inhibitor, reduces hypoxia in non-small cell lung cancer (NSCLC).
Patients and methods: Patients with NSCLC scheduled for surgery were recruited sequentially into two cohorts: Cohort 1 received oral atovaquone at the standard clinical dose 750 mg twice-daily whilst Cohort 2 did not. Primary imaging endpoint was change in tumor hypoxic volume (HV) measured by hypoxia PET-CT. Inter-cohort comparison of hypoxia gene expression signatures using RNAseq from resected tumors was performed.
Results: Thirty patients were evaluable for hypoxia PET-CT analysis, 15 per cohort. Median treatment duration was 12 days. Eleven (73.3%) atovaquone-treated patients had meaningful HV reduction with median change -28.0% (95% CI, -58.2 to -4.4). In contrast, median change in untreated patients was +15.5% (95% CI, -6.5 to 35.5). Linear regression estimated the expected mean HV was 55% (95% CI, 24% to 74%) lower in Cohort 1 compared to Cohort 2 (p=0.004), adjusting for cohort, tumor volume and baseline HV. A key pharmacodynamic endpoint was reduction in hypoxia regulated genes, which were significantly downregulated in atovaquone-treated tumors. Data from multiple additional measures of tumor hypoxia and perfusion are presented. No atovaquone-related adverse events were reported.
Conclusions: This is the first clinical evidence that targeting tumor mitochondrial metabolism can reduce hypoxia and produce relevant anti-tumor effects at the mRNA level. Repurposing atovaquone for this purpose may improve treatment outcomes for NSCLC