Towards an engineering theory of evolution

Effective biological engineering requires the acknowledgement of evolution and its consideration during the design process. In this perspective, the authors present the concept of the evotype to reason about and shape the evolutionary potential of natural and engineered biosystems

Circadian rhythmicity in emerging mood disorders: state or trait marker?

Background: Circadian rhythm disturbances overlap with the symptoms of mood episodes and may trigger or prolong mood symptoms. There is limited research on the role of circadian disturbances in mood disorders in young people and/or first episode cases of unipolar and bipolar disorders. Methods: Actigraphy was undertaken for about 14 days in 63 post-pubertal individuals aged 13–25 years with a recent onset of a mood disorder meeting recognised diagnostic criteria. We examined associations between three easily interpretable markers of circadian rhythm activity (amplitude, acrophase and rhythmicity index) and demography and clinical characteristics. Then, circadian markers were compared between diagnostic groups, controlling for potential confounders. Results: Longer duration of illness was correlated with reduced circadian rhythmicity and lower levels of activity over 24 h. A delay in the timing of maximum activity was associated with the level of manic but not depressive symptoms. The circadian rhythmicity index differentiated unipolar from bipolar cases, and in bipolar but not unipolar disorder, the rhythmicity was less robust in those with more severe manic or depressive symptoms. Conclusions: Less robust circadian rhythmicity, especially associated with increasing symptom severity, may represent a more specific or a trait marker of young people with mood disorders who are at higher risk of a bipolar course of illness

Mitigation of plasma-wall interactions with low-Z powders in DIII-D high confinement plasmas

Experiments with low-Z powder injection in DIII-D high confinement discharges demonstrated increased divertor dissipation and detachment while maintaining good core energy confinement. Lithium (Li), boron (B), and boron nitride (BN) powders were injected in high-confinement mode plasmas ($I_p=$1 MA, $B_t=$2 T, $P_{NB}=$6 MW, $\langle n_e\rangle=3.6-5.0\cdot10^{19}$ m$^{-3}$) into the upper small-angle slot (SAS) divertor for 2-s intervals at constant rates of 3-204 mg/s. The multi-species BN powders at a rate of 54 mg/s showed the most substantial increase in divertor neutral compression by more than an order of magnitude and lasting detachment with minor degradation of the stored magnetic energy $W_{mhd}$ by 5%. Rates of 204 mg/s of boron nitride powder further reduce ELM-fluxes on the divertor but also cause a drop in confinement performance by 24% due to the onset of an $n=2$ tearing mode. The application of powders also showed a substantial improvement of wall conditions manifesting in reduced wall fueling source and intrinsic carbon and oxygen content in response to the cumulative injection of non-recycling materials. The results suggest that low-Z powder injection, including mixed element compounds, is a promising new core-edge compatible technique that simultaneously enables divertor detachment and improves wall conditions during high confinement operation

Interlayer Registry Determines the Sliding Potential of Layered Metal Dichalcogenides: The case of 2H-MoS2

We provide a simple and intuitive explanation for the interlayer sliding energy landscape of metal dichalcogenides. Based on the recently introduced registry index (RI) concept, we define a purely geometrical parameter which quantifies the degree of interlayer commensurability in the layered phase of molybdenum disulphide (2HMoS2). A direct relation between the sliding energy landscape and the corresponding interlayer registry surface of 2H-MoS2 is discovered thus marking the registry index as a computationally efficient means for studying the tribology of complex nanoscale material interfaces in the wearless friction regime.Comment: 13 pages, 7 figure

NeuroSAFE frozen section during robot-assisted radical prostatectomy (RARP): Peri-operative and Histopathological Outcomes from the NeuroSAFE PROOF Feasibility Randomised Controlled Trial

Objectives: To report on the methods, peri‐operative outcomes and histopathological concordance between frozen and final section from the NeuroSAFE PROOF Feasibility study (NCT03317990). Patients and Methods: Between May 2018 and March 2019 49 men at 2 UK centres underwent robot‐assisted robotic prostatectomy (RARP). 25 men were randomised to NeuroSAFE RARP (intervention arm) vs. 24 men to standard RARP (control arm). Frozen section was compared to final paraffin section margin assessment in the 25 men in the NeuroSAFE arm. Operation timings and complications were collected prospectively in both arms. Results: 50 NVB from 25 patients in the NeuroSAFE arm were analysed. When analysed by each pathological section (n=250, average 5 per side) we note sensitivity 100%, specificity 99.2%, AUC was 0.994 (95% CI 0.985 to 1, P= <.001). On an NVB basis (n=50) we note sensitivity of 100%, specificity 92.7%, and AUC of 0.963 (95% CI 0.914 to 1, p = <0.001. NeuroSAFE RARP lasted a mean 3 hours 16 minutes (knife to skin to off table, 95% CI 3 hrs 2 mins ‐ 3 hrs 30 mins) compared to 2 hours 14 minutes (2 hrs 2 mins ‐ 2 hours 25 mins, P=<0.001) for standard RARP. There was no morbidity associated with the additional length of operation in the NeuroSAFE arm. Conclusion: This feasibility study demonstrates the safety, the reproducibility and the excellent histopathological concordance of the NeuroSAFE technique in the NeuroSAFE PROOF trial. Though the technique increases the duration of RARP, this does not cause short‐term harm. Confirmation of feasibility has led to the opening of the fully powered NeuroSAFE PROOF RCT, which is currently underway at 4 sites in the UK

Pedestal bifurcation and resonant field penetration at the threshold of edge-localized mode suppression in the DIII-D tokamak

Rapid bifurcations in the plasma response to slowly varying n=2 magnetic fields are observed as the plasma transitions into and out of edge-localized mode (ELM) suppression. The rapid transition to ELM suppression is characterized by an increase in the toroidal rotation and a reduction in the electron pressure gradient at the top of the pedestal that reduces the perpendicular electron flow there to near zero. These events occur simultaneously with an increase in the inner-wall magnetic response. These observations are consistent with strong resonant field penetration of n=2 fields at the onset of ELM suppression, based on extended MHD simulations using measured plasma profiles. Spontaneous transitions into (and out of) ELM suppression with a static applied n=2 field indicate competing mechanisms of screening and penetration of resonant fields near threshold conditions. Magnetic measurements reveal evidence for the unlocking and rotation of tearinglike structures as the plasma transitions out of ELM suppression.This work is supported by the U.S. Department of Energy under Awards No. DE-FC02-04ER54698, No. DE-AC02-09CH11466, No. DE-FG02-07ER54917, No. DE-FG02-89ER53296, No. DE-FG02-08ER54999, No. DE-FG02-08ER54984, No. DE-AC05-00OR22725, No. DE-FG02-86ER53218, and No. DE-FG02- 92ER54139

No evidence for cardiac dysfunction in Kif6 mutant mice.

A KIF6 variant in man has been reported to be associated with adverse cardiovascular outcomes after myocardial infarction. No clear biological or physiological data exist for Kif6. We sought to investigate the impact of a deleterious KIF6 mutation on cardiac function in mice. Kif6 mutant mice were generated and verified. Cardiac function was assessed by serial echocardiography at baseline, after ageing and after exercise. Lipid levels were also measured. No discernable adverse lipid or cardiac phenotype was detected in Kif6 mutant mice. These data suggest that dysfunction of Kif6 is linked to other more complex biological/biochemical parameters or is unlikely to be of material consequence in cardiac function