The study of animal foraging behaviour is of practical ecological importance, and exemplifies the wider scientific problem of optimizing search strategies. Lévy flights are random walks, the step ...lengths of which come from probability distributions with heavy power-law tails, such that clusters of short steps are connected by rare long steps. Lévy flights display fractal properties, have no typical scale, and occur in physical and chemical systems. An attempt to demonstrate their existence in a natural biological system presented evidence that wandering albatrosses perform Lévy flights when searching for prey on the ocean surface. This well known finding was followed by similar inferences about the search strategies of deer and bumblebees. These pioneering studies have triggered much theoretical work in physics (for example, refs), as well as empirical ecological analyses regarding reindeer, microzooplankton, grey seals, spider monkeys and fishing boats. Here we analyse a new, high-resolution data set of wandering albatross flights, and find no evidence for Lévy flight behaviour. Instead we find that flight times are gamma distributed, with an exponential decay for the longest flights. We re-analyse the original albatross data using additional information, and conclude that the extremely long flights, essential for demonstrating Lévy flight behaviour, were spurious. Furthermore, we propose a widely applicable method to test for power-law distributions using likelihood and Akaike weights. We apply this to the four original deer and bumblebee data sets, finding that none exhibits evidence of Lévy flights, and that the original graphical approach is insufficient. Such a graphical approach has been adopted to conclude Lévy flight movement for other organisms, and to propose Lévy flight analysis as a potential real-time ecosystem monitoring tool. Our results question the strength of the empirical evidence for biological Lévy flights.
Little is known about mechanisms of resistance to poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and platinum chemotherapy in patients with metastatic breast cancer and BRCA1/2 ...mutations. Further investigation of resistance in clinical cohorts may point to strategies to prevent or overcome treatment failure.
We obtained tumor biopsies from metastatic breast cancer patients with BRCA1/2 deficiency before and after acquired resistance to PARPi or platinum chemotherapy. Whole exome sequencing was carried out on each tumor, germline DNA, and circulating tumor DNA. Tumors underwent RNA sequencing, and immunohistochemical staining for RAD51 foci on tumor sections was carried out for functional assessment of intact homologous recombination (HR).
Pre- and post-resistance tumor samples were sequenced from eight patients (four with BRCA1 and four with BRCA2 mutation; four treated with PARPi and four with platinum). Following disease progression on DNA-damaging therapy, four patients (50%) acquired at least one somatic reversion alteration likely to result in functional BRCA1/2 protein detected by tumor or circulating tumor DNA sequencing. Two patients with germline BRCA1 deficiency acquired genomic alterations anticipated to restore HR through increased DNA end resection: loss of TP53BP1 in one patient and amplification of MRE11A in another. RAD51 foci were acquired post-resistance in all patients with genomic reversion, consistent with reconstitution of HR. All patients whose tumors demonstrated RAD51 foci post-resistance were intrinsically resistant to subsequent lines of DNA-damaging therapy.
Genomic reversion in BRCA1/2 was the most commonly observed mechanism of resistance, occurring in four of eight patients. Novel sequence alterations leading to increased DNA end resection were seen in two patients, and may be targetable for therapeutic benefit. The presence of RAD51 foci by immunohistochemistry was consistent with BRCA1/2 protein functional status from genomic data and predicted response to later DNA-damaging therapy, supporting RAD51 focus formation as a clinically useful biomarker.
•We analyzed mechanisms of resistance to PARP inhibitor/platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer.•Genomic reversion to functional BRCA1/2 protein was identified in one-half of patients.•Up-regulation of DNA end resection was identified as a resistance mechanism in two additional patients.•RAD51 foci assessed by immunohistochemistry correlated with clinical response to PARP inhibitor/platinum.•RAD51 focus staining warrants further exploration as a biomarker for clinical use.
Background: Research indicates that the chronic consumption of flavonoids is associated with cognitive benefits in adults with mild cognitive impairment and neurodegenerative disease, although to our ...knowledge, there have been no such studies in healthy older adults. Furthermore, the effects of commonly consumed orange juice flavanones on cognitive function remain unexplored. Objective: We investigated whether 8 wk of daily flavanone-rich orange juice consumption was beneficial for cognitive function in healthy older adults. Design: High-flavanone (305 mg) 100% orange juice and an equicaloric low-flavanone (37 mg) orange-flavored cordial (500 mL) were consumed daily for 8 wk by 37 healthy older adults (mean age: 67 y) according to a crossover, double-blind, randomized design separated by a 4-wk washout. Cognitive function, mood, and blood pressure were assessed at baseline and follow-up by using standardized validated tests. Results: Global cognitive function was significantly better after 8-wk consumption of flavanone-rich juice than after 8-wk consumption of the low-flavanone control. No significant effects on mood or blood pressure were observed. Conclusions: Chronic daily consumption of flavanone-rich 100% orange juice over 8 wk is beneficial for cognitive function in healthy older adults. The potential for flavanone-rich foods and drinks to attenuate cognitive decline in aging and the mechanisms that underlie these effects should be investigated. This trial was registered at clinicaltrials.gov as NCT01312610.
Testing theories of hierarchical structure formation requires estimating the distribution of galaxy morphologies and its change with redshift. One aspect of this investigation involves identifying ...galaxies with disturbed morphologies (e.g. merging galaxies). This is often done by summarizing galaxy images using, e.g. the concentration, asymmetry and clumpiness and Gini-M
20 statistics of Conselice and Lotz et al., respectively, and associating particular statistic values with disturbance. We introduce three statistics that enhance detection of disturbed morphologies at high redshift (z ∼ 2): the multimode (M), intensity (I) and deviation (D) statistics. We show their effectiveness by training a machine-learning classifier, random forest, using 1639 galaxies observed in the H band by the Hubble Space Telescope WFC3, galaxies that had been previously classified by eye by the Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey collaboration. We find that the MID statistics (and the A statistic of Conselice) are the most useful for identifying disturbed morphologies.
We also explore whether human annotators are useful for identifying disturbed morphologies. We demonstrate that they show limited ability to detect disturbance at high redshift, and that increasing their number beyond 10 does not provably yield better classification performance. We propose a simulation-based model-fitting algorithm that mitigates these issues by bypassing annotation.
ABSTRACT
Many scientific investigations of photometric galaxy surveys require redshift estimates, whose uncertainty properties are best encapsulated by photometric redshift (photo-z) posterior ...probability density functions (PDFs). A plethora of photo-z PDF estimation methodologies abound, producing discrepant results with no consensus on a preferred approach. We present the results of a comprehensive experiment comparing 12 photo-z algorithms applied to mock data produced for The Rubin Observatory Legacy Survey of Space and Time Dark Energy Science Collaboration. By supplying perfect prior information, in the form of the complete template library and a representative training set as inputs to each code, we demonstrate the impact of the assumptions underlying each technique on the output photo-z PDFs. In the absence of a notion of true, unbiased photo-z PDFs, we evaluate and interpret multiple metrics of the ensemble properties of the derived photo-z PDFs as well as traditional reductions to photo-z point estimates. We report systematic biases and overall over/underbreadth of the photo-z PDFs of many popular codes, which may indicate avenues for improvement in the algorithms or implementations. Furthermore, we raise attention to the limitations of established metrics for assessing photo-z PDF accuracy; though we identify the conditional density estimate loss as a promising metric of photo-z PDF performance in the case where true redshifts are available but true photo-z PDFs are not, we emphasize the need for science-specific performance metrics.
Photometric redshift estimation is an indispensable tool of precision cosmology. One problem that plagues the use of this tool in the era of large-scale sky surveys is that the bright galaxies that ...are selected for spectroscopic observation do not have properties that match those of (far more numerous) dimmer galaxies; thus, ill-designed empirical methods that produce accurate and precise redshift estimates for the former generally will not produce good estimates for the latter. In this paper, we provide a principled framework for generating conditional density estimates (i.e. photometric redshift PDFs) that takes into account selection bias and the covariate shift that this bias induces. We base our approach on the assumption that the probability that astronomers label a galaxy (i.e. determine its spectroscopic redshift) depends only on its measured (photometric and perhaps other) properties Formula: see text and not on its true redshift. With this assumption, we can explicitly write down risk functions that allow us to both tune and compare methods for estimating importance weights (i.e. the ratio of densities of unlabelled and labelled galaxies for different values of Formula: see text) and conditional densities. We also provide a method for combining multiple conditional density estimates for the same galaxy into a single estimate with better properties. We apply our risk functions to an analysis of ≈10
galaxies, mostly observed by Sloan Digital Sky Survey, and demonstrate through multiple diagnostic tests that our method achieves good conditional density estimates for the unlabelled galaxies.
The effect of the alloying elements Sn, Fe, Cr, Ni, Nb, and O on hydrogen-containing alpha-zirconium and zirconium hydrides is investigated using ab initio quantum mechanical calculations and ...classical simulations. Cr, Fe, and Ni atoms attract interstitially dissolved H atoms whereas interstitial oxygen atoms show no pronounced interaction with H atoms. The alloying elements destabilize the hydride phases in the order Sn>Fe>Cr>Ni>Nb. Hence, substitutional Sn (if atomically dispersed), Cr and Fe atoms are likely to delay hydride precipitation, effectively increasing the hydrogen solubility. Nb and Sn influence the mobility of Zr self-interstitial atoms (SIA’s), which diffuse rapidly and preferentially parallel to the basal planes forming interstitial dislocations loops perpendicular to the basal planes (a-loops). Nb suppresses this diffusion of SIA’s, thereby reducing the rate of formation of interstitial a-loops. Sn atoms, if present on substitutional sites, have a similar, but smaller effect. If SIA’s approach substitutional Fe, Cr, and Ni atoms, the simulations indicate a spontaneous swap promoting the smaller transition metal atoms into interstitial atoms, which diffuse very rapidly with a preference in the c-direction, thereby facilitating their segregation to energetically more favorable sites such as vacancies, vacancy c-loops, grain boundaries, surfaces, and intermetallic precipitates.
Many properties of complex porous media such as reservoir rocks are strongly affected by heterogeneity at different scales. Complex depositional and diagenetic processes have a strong control on the ...pore structures, leading to systems with a wide range of pore sizes covering many orders of magnitude in length scales. This poses a significant challenge for digital rock analysis since a single resolution image and associated simulation model cannot capture all the relevant length scales in sufficient detail due to limitations in computer memory and speed. The scale-transgressive effects of heterogeneity must therefore be accounted for through a multiscale digital rock workflow. We introduce a generalized multiscale imaging and pore-scale modelling workflow to derive transport properties of complex rocks having broad pore size distributions. A dry/wet micro-CT imaging sequence is used to spatially map the porosity and the connectivity of resolved and unresolved porous regions. The unresolved porosity regions are classified into different porosity classes or rock types. The resulting 3D rock-type map and the porosity map are combined and transformed into a multiscale pore network model. Resolved pores are treated in a conventional pore network manner while unresolved network elements are treated as a continuum Darcy-type porous medium. Similar to conventional continuum models, each Darcy pore is populated with single and multiphase flow properties. These properties are derived from high-resolution rock-type models constructed from backscatter SEM images and/or high-resolution micro-CT images of sub-samples. The multiscale digital rock workflow is applied to two heterogeneous rock samples: a mixed wet thinly laminated reservoir sandstone and an oil wet reservoir carbonate. Experimentally measured mercury–air primary drainage and oil–water imbibition capillary pressure curves (after ageing to restore wettability) are used to anchor the multiscale pore network model. Waterflood relative permeability is calculated in a blind test and compared with high-quality experimental data. A very encouraging agreement between computed and measured properties is found.
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