•A new algorithm for adaptive multidimensional integration is proposed.•It adds a new adaptive strategy to that used by the popular VEGAS algorithm.•It can greatly increase accuracy for integrands ...with diagonal structure.•VEGAS can be combined with other algorithms to make new hybrid algorithms.•The new algorithm can be substantially faster than MCMC.
We describe a new algorithm, vegas+, for adaptive multidimensional Monte Carlo integration. The new algorithm adds a second adaptive strategy, adaptive stratified sampling, to the adaptive importance sampling that is the basis for its widely used predecessor vegas. Both vegas and vegas+ are effective for integrands with large peaks, but vegas+ can be much more effective for integrands with multiple peaks or other significant structures aligned with diagonals of the integration volume. We give examples where vegas+ is 2–19× more accurate than vegas. We also show how to combine vegas+ with other integrators, such as the widely available miser algorithm, to make new hybrid integrators. For a different kind of hybrid, we show how to use integrand samples, generated using MCMC or other methods, to optimize vegas+ before integrating. We give an example where preconditioned vegas+ is more than 100× as efficient as vegas+ without preconditioning. Finally, we give examples where vegas+ is more than 10× as efficient as MCMC for Bayesian integrals with D=3 and 21 parameters. We explain why vegas+ will often outperform MCMC for small and moderate sized problems.
Entanglement of animals is one of the main environmental impacts of waste plastic. A 2015 review of entanglement records found that the proportion of affected seabirds increased from 16% of species ...to 25% over the last two decades. However, this was restricted to published records; Google Images and other web-based sources indicate that at least 147 seabird species (36%), as well as 69 freshwater birds (10%) and 49 landbirds (0.5%) from 53 families have been entangled in plastic or other synthetic materials. Fishing gear is responsible for entangling most species (83%), although it is often difficult to differentiate entanglement from bycatch on active gear. Mitigation measures include banning high-risk applications where there are alternatives (e.g. six-pack rings), discouraging the use of high-risk items (e.g. balloons on strings, ‘manja’ kites), and encouraging fishers to not discard waste fishing gear by providing specific receptacles and associated educational signage in fishing areas.
•55% of bird orders and 21% of bird families are recorded to be entangled in plastic.•36% of seabird species are now known to be entangled in plastic litter.•Freshwater birds (10% of species) have less risk of entanglement than seabirds.•Fishing gear entangles 83% of the 265 entangled bird species globally.•The fairly small set of problem items allows for targeted mitigation measures.
Gout is a common inflammatory arthritis caused by precipitation of monosodium urate (MSU) crystals in individuals with hyperuricemia. Acute flares are accompanied by secretion of proinflammatory ...cytokines, including interleukin-1β (IL-1β). Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition predisposing to hematologic cancers and cardiovascular disease. CHIP is associated with elevated IL-1β, thus we investigated CHIP as a risk factor for gout. To test the clinical association between CHIP and gout, we analyzed whole exome sequencing data from 177 824 individuals in the MGB Biobank (MGBB) and UK Biobank (UKB). In both cohorts, the frequency of gout was higher among individuals with CHIP than without CHIP (MGBB, CHIP with variant allele fraction VAF ≥2%: odds ratio OR, 1.69; 95% CI, 1.09-2.61; P = .0189; UKB, CHIP with VAF ≥10%: OR, 1.25; 95% CI, 1.05-1.50; P = .0133). Moreover, individuals with CHIP and a VAF ≥10% had an increased risk of incident gout (UKB: hazard ratio HR, 1.28; 95% CI, 1.06-1.55; P = .0107). In murine models of gout pathogenesis, animals with Tet2 knockout hematopoietic cells had exaggerated IL-1β secretion and paw edema upon administration of MSU crystals. Tet2 knockout macrophages elaborated higher levels of IL-1β in response to MSU crystals in vitro, which was ameliorated through genetic and pharmacologic Nlrp3 inflammasome inhibition. These studies show that TET2-mutant CHIP is associated with an increased risk of gout in humans and that MSU crystals lead to elevated IL-1β levels in Tet2 knockout murine models. We identify CHIP as an amplifier of NLRP3-dependent inflammatory responses to MSU crystals in patients with gout.
•TET2-mutant clonal hematopoiesis is associated with increased risk of incident gout.•Monosodium urate crystal treatment exacerbates Nlrp3-dependent IL-1β secretion and functional impairment in transplanted Tet2-knockout mice.
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The formation of crystalline nanoparticles starts with nucleation and control of nucleation is crucial for the control of the number, size, perfection, polymorph modification and other ...characteristics of particles. Recently, there have been significant advances in the understanding of the mechanism of nucleation of crystals in solution. The most significant of these is the two-step mechanism of nucleation, according to which the crystalline nucleus appears inside pre-existing metastable clusters of size several hundred nanometers, which consist of dense liquid and are suspended in the solution. While initially proposed for protein crystals, the applicability of this mechanism has been demonstrated for small-molecule organic and inorganic materials, colloids, and biominerals. This mechanism helps to explain several long-standing puzzles of crystal nucleation in solution: nucleation rates which are many orders of magnitude lower than theoretical predictions, nucleation kinetic dependencies with steady or receding parts at increasing supersaturation, the role of heterogeneous substrates for polymorph selection, the significance of the dense protein liquid, and others. More importantly, this mechanism provides powerful tools for control of the nucleation process by varying the solution thermodynamic parameters so that the volume occupied by the dense liquid shrinks or expands.
The formation of nanocrystals in solution may follow a two-step mechanism of nucleation, whereby a dense liquid droplet serves as a precursor to the ordered nucleus.
Boson Sampling on a Photonic Chip Spring, Justin B.; Metcalf, Benjamin J.; Humphreys, Peter C. ...
Science (American Association for the Advancement of Science),
02/2013, Letnik:
339, Številka:
6121
Journal Article
Recenzirano
Odprti dostop
Although universal quantum computers ideally solve problems such as factoring integers exponentially more efficiently than classical machines, the formidable challenges in building such devices ...motivate the demonstration of simpler, problem-specific algorithms that still promise a quantum speedup. We constructed a quantum boson-sampling machine (QBSM) to sample the output distribution resulting from the nonclassical interference of photons in an integrated photonic circuit, a problem thought to be exponentially hard to solve classically. Unlike universal quantum computation, boson sampling merely requires indistinguishable photons, linear state evolution, and detectors. We benchmarked our QBSM with three and four photons and analyzed sources of sampling inaccuracy. Scaling up to larger devices could offer the first definitive quantum-enhanced computation.
Protein folding has been viewed as a difficult problem of molecular self-organization. The search problem involved in folding however has been simplified through the evolution of folding energy ...landscapes that are funneled. The funnel hypothesis can be quantified using energy landscape theory based on the minimal frustration principle. Strong quantitative predictions that follow from energy landscape theory have been widely confirmed both through laboratory folding experiments and from detailed simulations. Energy landscape ideas also have allowed successful protein structure prediction algorithms to be developed.
The selection constraint of having funneled folding landscapes has left its imprint on the sequences of existing protein structural families. Quantitative analysis of co-evolution patterns allows us to infer the statistical characteristics of the folding landscape. These turn out to be consistent with what has been obtained from laboratory physicochemical folding experiments signaling a beautiful confluence of genomics and chemical physics.
•Funneled landscapes explain the paradoxes of robust protein folding.•Energy landscape theory leads to structure prediction tools.•Comparing evolution data with landscapes quantifies the frustration of folding.
Floating persistent debris, primarily made from plastic, disperses long distances from source areas and accumulates in oceanic gyres. However, biofouling can increase the density of debris items to ...the point where they sink. Buoyancy is related to item volume, whereas fouling is related to surface area, so small items (which have high surface area to volume ratios) should start to sink sooner than large items. Empirical observations off South Africa support this prediction: moving offshore from coastal source areas there is an increase in the size of floating debris, an increase in the proportion of highly buoyant items (e.g. sealed bottles, floats and foamed plastics), and a decrease in the proportion of thin items such as plastic bags and flexible packaging which have high surface area to volume ratios. Size-specific sedimentation rates may be one reason for the apparent paucity of small plastic items floating in the world's oceans.
The purpose of this review is to describe the endocrine and local testicular factors that contribute to the regulation of the blood-testis barrier (BTB), using information gained from in vivo and in ...vitro models of BTB formation during/after puberty, and from the maintenance of BTB function during adulthood. In vivo the BTB, in part comprised of tight junctions between adjacent somatic Sertoli cells, compartmentalizes meiotic spermatocytes and post-meiotic spermatids away from the vasculature, and therefore prevents autoantibody production by the immune system against these immunogenic germ cells. This adluminal compartment also features a unique biochemical milieu required for the completion of germ cell development. During the normal process of spermatogenesis, earlier germ cells continually cross into the adluminal compartment, but the regulatory mechanisms and changes in junctional proteins that allow this translocation step without causing a 'leak' remain poorly understood. Recent data describing the roles of FSH and androgen on the regulation of Sertoli cell tight junctions and tight junction proteins will be discussed, followed by an examination of the role of paracrine factors, including members of the TGFβ superfamily (TGFβ3, activin A) and retinoid signalling, as potential mediators of junction assembly and disassembly during the translocation process.
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