2,107 research outputs found
The potential impact of Brexit on the energy, water and food nexus in the UK: A fuzzy cognitive mapping approach
© 2017 The Authors. Energy is one of the cornerstones essential for human life, along with other services such as water and food. Understanding how the different services in the energy-water-food (EWF) nexus interact and are perceived by different actors is key to achieving sustainability. In this paper, we derive a model of the EWF nexus using fuzzy cognitive mapping (FCM). Data were collected in a two-step approach from workshops with researchers and stakeholders involved in the three focal sectors. Four FCMs were developed; one for each of the EWF sectors, and one for the interactions that create the nexus between EWF. The FCM represents the combined views of the groups who participated in the workshops, the importance and limitations of which is discussed. To demonstrate its effectiveness, the aggregated FCM was applied to predict the impacts on the EWF nexus of four scenarios under which the United Kingdom would depart from the European Union (i.e. Brexit). The FCM indicated that energy-related concepts had the largest influence on the EWF nexus and that EWF demand will decrease most under a 'hard-Brexit' scenario. The demand for energy was shown to decline relatively less than other services and was strongly associated with gross domestic product (GDP), whereas UK population size had a stronger effect on water and food demand. Overall, we found a threefold change across all concepts in scenarios without freedom of movement, contribution to the EU budget, and increased policy devolution to the UK
Computer-Generated Ovaries to Assist Follicle Counting Experiments
Precise estimation of the number of follicles in ovaries is of key importance in the field of reproductive biology, both from a developmental point of view, where follicle numbers are determined at specific time points, as well as from a therapeutic perspective, determining the adverse effects of environmental toxins and cancer chemotherapeutics on the reproductive system. The two main factors affecting follicle number estimates are the sampling method and the variation in follicle numbers within animals of the same strain, due to biological variability. This study aims at assessing the effect of these two factors, when estimating ovarian follicle numbers of neonatal mice. We developed computer algorithms, which generate models of neonatal mouse ovaries (simulated ovaries), with characteristics derived from experimental measurements already available in the published literature. The simulated ovaries are used to reproduce in-silico counting experiments based on unbiased stereological techniques; the proposed approach provides the necessary number of ovaries and sampling frequency to be used in the experiments given a specific biological variability and a desirable degree of accuracy. The simulated ovary is a novel, versatile tool which can be used in the planning phase of experiments to estimate the expected number of animals and workload, ensuring appropriate statistical power of the resulting measurements. Moreover, the idea of the simulated ovary can be applied to other organs made up of large numbers of individual functional units
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Endogenous miRNA in the green alga Chlamydomonas regulates gene expression through CDS-targeting
MicroRNAs regulate gene expression as part of the RNA-induced silencing complex, for which the sequence identity of the miRNA provides the specificity to the target messenger RNA and the result is target repression. The mode of repression can be through target cleavage, RNA destabilization and/or decreased translational efficiency. Here, we provide a comprehensive global analysis of the evolutionarily distant unicellular green alga Chlamydomonas reinhardtii to quantify the effects of miRNA on protein synthesis and RNA abundance. We show that, similar to metazoan steady-state systems, endogenous miRNAs in Chlamydomonas can regulate gene-expression both by destabilization of the mRNA and by translational repression. However, unlike metazoan miRNA where target site utilization localizes mainly to 3'UTRs, in Chlamydomonas utilized target sites lie predominantly within coding regions. These results demonstrate the evolutionarily conserved mode of action for miRNAs, but details of the mechanism diverge between plant and metazoan kingdoms.This work was supported by a Balzan Prize award and the European Research Council Advanced Investigator Grant ERC-2013-AdG 340642 TRIBE. B.Y.W.C. was supported by an EMBO long-term postdoctoral fellowship and a Sir Henry Wellcome Fellowship [096082]. D.C.B. is the Royal Society Edward Penley Abraham Research Professor
Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale
The detection of sound begins when energy derived from acoustic stimuli
deflects the hair bundles atop hair cells. As hair bundles move, the viscous
friction between stereocilia and the surrounding liquid poses a fundamental
challenge to the ear's high sensitivity and sharp frequency selectivity. Part
of the solution to this problem lies in the active process that uses energy for
frequency-selective sound amplification. Here we demonstrate that a
complementary part involves the fluid-structure interaction between the liquid
within the hair bundle and the stereocilia. Using force measurement on a
dynamically scaled model, finite-element analysis, analytical estimation of
hydrodynamic forces, stochastic simulation and high-resolution interferometric
measurement of hair bundles, we characterize the origin and magnitude of the
forces between individual stereocilia during small hair-bundle deflections. We
find that the close apposition of stereocilia effectively immobilizes the
liquid between them, which reduces the drag and suppresses the relative
squeezing but not the sliding mode of stereociliary motion. The obliquely
oriented tip links couple the mechanotransduction channels to this least
dissipative coherent mode, whereas the elastic horizontal top connectors
stabilize the structure, further reducing the drag. As measured from the
distortion products associated with channel gating at physiological stimulation
amplitudes of tens of nanometres, the balance of forces in a hair bundle
permits a relative mode of motion between adjacent stereocilia that encompasses
only a fraction of a nanometre. A combination of high-resolution experiments
and detailed numerical modelling of fluid-structure interactions reveals the
physical principles behind the basic structural features of hair bundles and
shows quantitatively how these organelles are adapted to the needs of sensitive
mechanotransduction.Comment: 21 pages, including 3 figures. For supplementary information, please
see the online version of the article at http://www.nature.com/natur
Does BCR/ABL1 positive Acute Myeloid Leukaemia Exist?
The BCR/ABL1 fusion gene, usually carried by the Philadelphia chromosome (Ph) resulting from t(9;22)(q34;q11) or variants, is pathognomonic for chronic myeloid leukaemia (CML). It is also occasionally found in acute lymphoblastic leukaemia (ALL) mostly in adults and rarely in de novo acute myeloid leukaemia (AML). Array Comparative Genomic Hybridization (aCGH) was used to study six Ph(+)AML, three bi-lineage and four Ph(+)ALL searching for specific genomic profiles. Surprisingly, loss of the IKZF1 and/or CDKN2A genes, the hallmark of Ph(+)ALL, were recurrent findings in Ph(+)AML and accompanied cryptic deletions within the immunoglobulin and T cell receptor genes. The latter two losses have been shown to be part of 'hot spot' genome imbalances associated with BCR/ABL1 positive pre-B lymphoid phenotype in CML and Ph(+)ALL. We applied Significance Analysis of Microarrays (SAM) to data from the 'hot spot' regions to the Ph(+)AML and a further 40 BCR/ABL1(+) samples looking for differentiating features. After exclusion of the most dominant markers, SAM identified aberrations unique to de novo Ph(+)AML that involved relevant genes. While the biological and clinical significance of this specific genome signature remains to be uncovered, the unique loss within the immunoglobulin genes provides a simple test to enable the differentiation of clinically similar de novo Ph(+) AML and myeloid blast crisis of CML. © 2013 John Wiley & Sons Ltd and Crown
Impact of Parental Mental Health and Poverty on the Health of the Next Generation: A Multi-Trajectory Analysis Using the UK Millennium Cohort Study
Telephone-administered psychotherapy for depression in MS patients: moderating role of social support
Depression is common in individuals with multiple sclerosis (MS). While psychotherapy is an effective treatment for depression, not all individuals benefit. We examined whether baseline social support might differentially affect treatment outcome in 127 participants with MS and depression randomized to either Telephone-administered Cognitive-Behavioral Therapy (T-CBT) or Telephone-administered Emotion-Focused Therapy (T-EFT). We predicted that those with low social support would improve more in T-EFT, since this approach emphasizes the therapeutic relationship, while participants with strong social networks and presumably more emotional resources might fare better in the more structured and demanding T-CBT. We found that both level of received support and satisfaction with that support at baseline did moderate treatment outcome. Individuals with high social support showed a greater reduction in depressive symptoms in the T-CBT as predicted, but participants with low social support showed a similar reduction in both treatments. This suggests that for participants with high social support, CBT may be a more beneficial treatment for depression compared with EFT
Cost-effectiveness analysis of preoperative transfusion in patients with sickle cell disease using evidence from the TAPS trial.
The study's objective was to assess the cost-effectiveness of preoperative transfusion compared with no preoperative transfusion in patients with sickle cell disease undergoing low- or medium-risk surgery. Seventy patients with sickle cell disease (HbSS/Sß(0) thal genotypes) undergoing elective surgery participated in a multicentre randomised trial, Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS). Here, a cost-effectiveness analysis based on evidence from that trial is presented. A decision-analytic model is used to incorporate long-term consequences of transfusions and acute chest syndrome. Costs and health benefits, expressed as quality-adjusted life years (QALYs), are reported from the 'within-trial' analysis and for the decision-analytic model. The probability of cost-effectiveness for each form of management is calculated taking into account the small sample size and other sources of uncertainty. In the range of scenarios considered in the analysis, preoperative transfusion was more effective, with the mean improvement in QALYs ranging from 0.018 to 0.206 per patient, and also less costly in all but one scenario, with the mean cost difference ranging from -£813 to £26. All scenarios suggested preoperative transfusion had a probability of cost-effectiveness >0.79 at a cost-effectiveness threshold of £20 000 per QALY
Syntactic processing as a marker for cognitive impairment in amyotrophic lateral sclerosis
Despite recent interest in cognitive changes in patients with amyotrophic lateral sclerosis (ALS), investigations of language function looking at the level of word, sentence and discourse processing are relatively scarce. Data were obtained from 26 patients with sporadic ALS and 26 healthy controls matched for age, education, gender, anxiety, depression and executive function performance. Standardized language tasks included confrontation naming, semantic access, and syntactic comprehension. Quantitative production analysis (QPA) was used to analyse connected speech samples of the Cookie Theft picture description task. Results showed that the ALS patients were impaired on standardized measures of grammatical comprehension and action/verb semantics. At the level of discourse, ALS patients were impaired on measures of syntactic complexity and fluency; however, the latter could be better explained by disease related factors. Discriminant analysis revealed that syntactic measures differentiated ALS patients from controls. In conclusion, patients with ALS exhibit deficits in receptive and expressive language on tasks of comprehension and connected speech production, respectively. Our findings suggest that syntactic processing deficits seem to be the predominant feature of language impairment in ALS and that these deficits can be detected by relatively simple language tests
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