Structure of the moiré exciton captured by imaging its electron and hole.

Interlayer excitons (ILXs) - electron-hole pairs bound across two atomically thin layered semiconductors - have emerged as attractive platforms to study exciton condensation1-4, single-photon emission and other quantum information applications5-7. Yet, despite extensive optical spectroscopic investigations8-12, critical information about their size, valley configuration and the influence of the moiré potential remains unknown. Here, in a WSe2/MoS2 heterostructure, we captured images of the time-resolved and momentum-resolved distribution of both of the particles that bind to form the ILX: the electron and the hole. We thereby obtain a direct measurement of both the ILX diameter of around 5.2 nm, comparable with the moiré-unit-cell length of 6.1 nm, and the localization of its centre of mass. Surprisingly, this large ILX is found pinned to a region of only 1.8 nm diameter within the moiré cell, smaller than the size of the exciton itself. This high degree of localization of the ILX is backed by Bethe-Salpeter equation calculations and demonstrates that the ILX can be localized within small moiré unit cells. Unlike large moiré cells, these are uniform over large regions, allowing the formation of extended arrays of localized excitations for quantum technology.

Photoconductive arrays on insulating substrates for high-field terahertz generation.

We report on the design, fabrication and characterisation of large-area photoconductive THz array structures, consisting of a thin LT-GaAs active region transferred to an insulating substrate using a wafer-scale bonding process. The electrically insulating, transparent substrate reduces the parasitic currents in the devices, allowing peak THz-fields as high as 120 kV cm-1 to be generated over a bandwidth >5 THz. These results are achieved using lower pulse energies than demanded by conventional photoconductive arrays and other popular methods of generating high-field THz radiation. Two device sizes are fully characterised and the emission properties are compared to generation by optical rectification in ZnTe. The device can be operated in an optically saturated regime in order to suppress laser noise.

Forecasting national and regional influenza-like illness for the USA.

Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.

Cosmology and fundamental physics with the Euclid satellite.

Euclid is a European Space Agency medium-class mission selected for launch in 2020 within the cosmic vision 2015-2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid's Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.

Testing the Speed of Gravitational Waves over Cosmological Distances with Strong Gravitational Lensing.

Probing the relative speeds of gravitational waves and light acts as an important test of general relativity and alternative theories of gravity. Measuring the arrival time of gravitational waves (GWs) and electromagnetic (EM) counterparts can be used to measure the relative speeds, but only if the intrinsic time lag between emission of the photons and gravitational waves is well understood. Here we suggest a method that does not make such an assumption, using future strongly lensed GW events and EM counterparts; Biesiada et al. [J. Cosmol. Astropart. Phys.10 (2014) 080JCAPBP1475-751610.1088/1475-7516/2014/10/080] forecast that 50-100 strongly lensed GW events will be observed each year with the Einstein Telescope. A single strongly lensed GW event would produce robust constraints on c_{GW}/c_{γ} at the 10^{-7} level, if a high-energy EM counterpart is observed within the field of view of an observing γ-ray burst monitor.

Free-space terahertz radiation from a LT-GaAs-on-quartz large-area photoconductive emitter.

We report on large-area photoconductive terahertz (THz) emitters with a low-temperature-grown GaAs (LT-GaAs) active layer fabricated on quartz substrates using a lift-off transfer process. These devices are compared to the same LT-GaAs emitters when fabricated on the growth substrate. We find that the transferred devices show higher optical-to-THz conversion efficiencies and significantly larger breakdown fields, which we attribute to reduced parasitic current in the substrate. Through these improvements, we demonstrate a factor of ~8 increase in emitted THz field strength at the maximum operating voltage. In addition we find improved performance when these devices are used for photoconductive detection, which we explain through a combination of reduced parasitic substrate currents and reduced space-charge build-up in the device.

Early Characterization of the Severity and Transmissibility of Pandemic Influenza Using Clinical Episode Data from Multiple Populations.

The potential rapid availability of large-scale clinical episode data during the next influenza pandemic suggests an opportunity for increasing the speed with which novel respiratory pathogens can be characterized. Key intervention decisions will be determined by both the transmissibility of the novel strain (measured by the basic reproductive number R0) and its individual-level severity. The 2009 pandemic illustrated that estimating individual-level severity, as described by the proportion pC of infections that result in clinical cases, can remain uncertain for a prolonged period of time. Here, we use 50 distinct US military populations during 2009 as a retrospective cohort to test the hypothesis that real-time encounter data combined with disease dynamic models can be used to bridge this uncertainty gap. Effectively, we estimated the total number of infections in multiple early-affected communities using the model and divided that number by the known number of clinical cases. Joint estimates of severity and transmissibility clustered within a relatively small region of parameter space, with 40 of the 50 populations bounded by: pC, 0.0133-0.150 and R0, 1.09-2.16. These fits were obtained despite widely varying incidence profiles: some with spring waves, some with fall waves and some with both. To illustrate the benefit of specific pairing of rapidly available data and infectious disease models, we simulated a future moderate pandemic strain with pC approximately ×10 that of 2009; the results demonstrating that even before the peak had passed in the first affected population, R0 and pC could be well estimated. This study provides a clear reference in this two-dimensional space against which future novel respiratory pathogens can be rapidly assessed and compared with previous pandemics.

The evolutionary history of Plasmodium vivax as inferred from mitochondrial genomes: parasite genetic diversity in the Americas.

Plasmodium vivax is the most prevalent human malaria parasite in the Americas. Previous studies have contrasted the genetic diversity of parasite populations in the Americas with those in Asia and Oceania, concluding that New World populations exhibit low genetic diversity consistent with a recent introduction. Here we used an expanded sample of complete mitochondrial genome sequences to investigate the diversity of P. vivax in the Americas as well as in other continental populations. We show that the diversity of P. vivax in the Americas is comparable to that in Asia and Oceania, and we identify several divergent clades circulating in South America that may have resulted from independent introductions. In particular, we show that several haplotypes sampled in Venezuela and northeastern Brazil belong to a clade that diverged from the other P. vivax lineages at least 30,000 years ago, albeit not necessarily in the Americas. We propose that, unlike in Asia where human migration increases local genetic diversity, the combined effects of the geographical structure and the low incidence of vivax malaria in the Americas has resulted in patterns of low local but high regional genetic diversity. This could explain previous views that P. vivax in the Americas has low genetic diversity because these were based on studies carried out in limited areas. Further elucidation of the complex geographical pattern of P. vivax variation will be important both for diversity assessments of genes encoding candidate vaccine antigens and in the formulation of control and surveillance measures aimed at malaria elimination.

Multiple estimates of transmissibility for the 2009 influenza pandemic based on influenza-like-illness data from small US military populations.

Rapidly characterizing the amplitude and variability in transmissibility of novel human influenza strains as they emerge is a key public health priority. However, comparison of early estimates of the basic reproduction number during the 2009 pandemic were challenging because of inconsistent data sources and methods. Here, we define and analyze influenza-like-illness (ILI) case data from 2009-2010 for the 50 largest spatially distinct US military installations (military population defined by zip code, MPZ). We used publicly available data from non-military sources to show that patterns of ILI incidence in many of these MPZs closely followed the pattern of their enclosing civilian population. After characterizing the broad patterns of incidence (e.g. single-peak, double-peak), we defined a parsimonious SIR-like model with two possible values for intrinsic transmissibility across three epochs. We fitted the parameters of this model to data from all 50 MPZs, finding them to be reasonably well clustered with a median (mean) value of 1.39 (1.57) and standard deviation of 0.41. An increasing temporal trend in transmissibility ([Formula: see text], p-value: 0.013) during the period of our study was robust to the removal of high transmissibility outliers and to the removal of the smaller 20 MPZs. Our results demonstrate the utility of rapidly available - and consistent - data from multiple populations.

Genetic variation and recurrent parasitaemia in Peruvian Plasmodium vivax populations.

BACKGROUND: Plasmodium vivax is a predominant species of malaria in parts of South America and there is increasing resistance to drugs to treat infections by P. vivax. The existence of latent hypnozoites further complicates the ability to classify recurrent infections as treatment failures due to relapse, recrudescence of hyponozoites or re-infections. Antigen loci are putatively under natural selection and may not be an optimal molecular marker to define parasite haplotypes in paired samples. Putatively neutral microsatellite loci, however, offer an assessment of neutral haplotypes. The objective here was to assess the utility of neutral microsatellite loci to reconcile cases of recurrent parasitaemia in Amazonian P. vivax populations in Peru. METHODS: Patient blood samples were collected from three locations in or around Iquitos in the Peruvian Amazon. Five putatively neutral microsatellite loci were characterized from 445 samples to ascertain the within and amongst population variation. A total of 30 day 0 and day of recurrent parasitaemia samples were characterized at microsatellite loci and five polymorphic antigen loci for haplotype classification. RESULTS: The genetic diversity at microsatellite loci was consistent with neutral levels of variation measured in other South American P. vivax populations. Results between antigen and microsatellite loci for the 30 day 0 and day of recurrent parasitaemia samples were the same for 80% of the pairs. The majority of non-concordant results were the result of differing alleles at microsatellite loci. This analysis estimates that 90% of the paired samples with the same microsatellite haplotype are unlikely to be due to a new infection. CONCLUSIONS: A population-level approach was used to yield a better estimate of the probability of a new infection versus relapse or recrudescence of homologous hypnozoites; hypnozoite activation was common for this cohort. Population studies are critical with the evaluation of genetic markers to assess P. vivax biology and epidemiology. The additional demonstration of microsatellite loci as neutral markers capable of distinguishing the origin of the recurrent parasites (new infection or originating from the patient) lends support to their use in assessment of treatment outcomes.

Genome scanning of Amazonian Plasmodium falciparum shows subtelomeric instability and clindamycin-resistant parasites.

Here, we fully characterize the genomes of 14 Plasmodium falciparum patient isolates taken recently from the Iquitos region using genome scanning, a microarray-based technique that delineates the majority of single-base changes, indels, and copy number variants distinguishing the coding regions of two clones. We show that the parasite population in the Peruvian Amazon bears a limited number of genotypes and low recombination frequencies. Despite the essentially clonal nature of some isolates, we see high frequencies of mutations in subtelomeric highly variable genes and internal var genes, indicating mutations arising during self-mating or mitotic replication. The data also reveal that one or two meioses separate different isolates, showing that P. falciparum clones isolated from different individuals in defined geographical regions could be useful in linkage analyses or quantitative trait locus studies. Through pairwise comparisons of different isolates we discovered point mutations in the apicoplast genome that are close to known mutations that confer clindamycin resistance in other species, but which were hitherto unknown in malaria parasites. Subsequent drug sensitivity testing revealed over 100-fold increase of clindamycin EC(50) in strains harboring one of these mutations. This evidence of clindamycin-resistant parasites in the Amazon suggests that a shift should be made in health policy away from quinine + clindamycin therapy for malaria in pregnant women and infants, and that the development of new lincosamide antibiotics for malaria should be reconsidered.

Antilensing: the bright side of voids.

More than half of the volume of our Universe is occupied by cosmic voids. The lensing magnification effect from those underdense regions is generally thought to give a small dimming contribution: objects on the far side of a void are supposed to be observed as slightly smaller than if the void were not there, which together with conservation of surface brightness implies net reduction in photons received. This is predicted by the usual weak lensing integral of the density contrast along the line of sight. We show that this standard effect is swamped at low redshifts by a relativistic Doppler term that is typically neglected. Contrary to the usual expectation, objects on the far side of a void are brighter than they would be otherwise. Thus the local dynamics of matter in and near the void is crucial and is only captured by the full relativistic lensing convergence. There are also significant nonlinear corrections to the relativistic linear theory, which we show actually underpredicts the effect. We use exact solutions to estimate that these can be more than 20% for deep voids. This remains an important source of systematic errors for weak lensing density reconstruction in galaxy surveys and for supernovae observations, and may be the cause of the reported extra scatter of field supernovae located on the edge of voids compared to those in clusters.

Dark matter maps reveal cosmic scaffolding.

Ordinary baryonic particles (such as protons and neutrons) account for only one-sixth of the total matter in the Universe. The remainder is a mysterious 'dark matter' component, which does not interact via electromagnetism and thus neither emits nor reflects light. As dark matter cannot be seen directly using traditional observations, very little is currently known about its properties. It does interact via gravity, and is most effectively probed through gravitational lensing: the deflection of light from distant galaxies by the gravitational attraction of foreground mass concentrations. This is a purely geometrical effect that is free of astrophysical assumptions and sensitive to all matter--whether baryonic or dark. Here we show high-fidelity maps of the large-scale distribution of dark matter, resolved in both angle and depth. We find a loose network of filaments, growing over time, which intersect in massive structures at the locations of clusters of galaxies. Our results are consistent with predictions of gravitationally induced structure formation, in which the initial, smooth distribution of dark matter collapses into filaments then into clusters, forming a gravitational scaffold into which gas can accumulate, and stars can be built.

Cosmology and Fundamental Physics with the Euclid Satellite.

Euclid is a European Space Agency medium-class mission selected for launch in 2019 within the Cosmic Vision 2015-2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid's Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.

COVID-19: On the Disparity in Outcomes Between Military and Civilian Populations.

INTRODUCTION: The CoronaVirus Disease 2019 (COVID-19) pandemic remains a formidable threat to populations around the world. The U.S. Military, in particular, represents a unique and distinguishable subset of the population, primarily due to the age and gender of active duty personnel. Current investigations have focused on health outcome forecasts for civilian populations, making them of limited value for military planning. MATERIALS AND METHODS: We have developed and applied an age-structured susceptible, exposed, infectious, recovered, or dead compartmental model for both civilian and military populations, driven by estimates of the time-dependent reproduction number, R(t), which can be both fit to available data and also forecast future cases, intensive care unit (ICU) patients, and deaths. RESULTS: We show that the expected health outcomes for active duty military populations are substantially different than for civilian populations of the same size. Specifically, while the number of cases is not expected to differ dramatically, severity, both in terms of ICU burdens and deaths, is substantially lower. CONCLUSIONS: Our results confirm that the burden placed on military health centers will be substantially lower than that for equivalent-sized civilian populations. More practically, the tool we have developed to investigate this (https://q.predsci.com/covid19/) can be used by military health planners to estimate the resources needed in particular locations based on current estimates of the transmission profiles of COVID-19 within the surrounding civilian population in which the military installation is embedded. As this tool continues to be developed, it can be used to assess the likely impact of different intervention strategies, as well as vaccine policies; both for the current pandemic as well as future ones.

Genetic diversity and population structure of genes encoding vaccine candidate antigens of Plasmodium vivax.

BACKGROUND: A major concern in malaria vaccine development is genetic polymorphisms typically observed among Plasmodium isolates in different geographical areas across the world. Highly polymorphic regions have been observed in Plasmodium falciparum and Plasmodium vivax antigenic surface proteins such as Circumsporozoite protein (CSP), Duffy-binding protein (DBP), Merozoite surface protein-1 (MSP-1), Apical membrane antigen-1 (AMA-1) and Thrombospondin related anonymous protein (TRAP). METHODS: Genetic variability was assessed in important polymorphic regions of various vaccine candidate antigens in P. vivax among 106 isolates from the Amazon Region of Loreto, Peru. In addition, genetic diversity determined in Peruvian isolates was compared to population studies from various geographical locations worldwide. RESULTS: The structured diversity found in P. vivax populations did not show a geographic pattern and haplotypes from all gene candidates were distributed worldwide. In addition, evidence of balancing selection was found in polymorphic regions of the trap, dbp and ama-1 genes. CONCLUSIONS: It is important to have a good representation of the haplotypes circulating worldwide when implementing a vaccine, regardless of the geographic region of deployment since selective pressure plays an important role in structuring antigen diversity.

Optimum excitation wavelength and photon energy threshold for spintronic terahertz emission from Fe/Pt bilayer.

Terahertz emission from ferromagnetic/non-magnetic spintronic heterostructures had been demonstrated as pump wavelength-independent. We report, however, the pump wavelength dependence of terahertz emission from an optimized Fe/Pt spintronic bilayer on MgO substrate. Maximum terahertz generation per total pump power was observed in the 1200- to 1800-nm pump wavelength range, and a marked decrease in the terahertz emission efficiency beyond 2500 nm (pump photon energies <0.5 eV) suggests a ∼0.35-eV threshold pump photon energy for effective spintronic terahertz emission. The inferred threshold is supported by previous theoretical results on the onset energy of significant spin-filtering at the Fe-Pt interface, and confirmed by Fe/Pt electronic structure calculations in this present work. The results of terahertz time-domain emission spectroscopy show the sensitivity of spintronic terahertz emission to both the optical absorptance of the heterostructure and the energy-dependent spin transport, as dictated by the properties of the metallic thin films.

Experimental measurement of the intrinsic excitonic wave function.

An exciton, a two-body composite quasiparticle formed of an electron and hole, is a fundamental optical excitation in condensed matter systems. Since its discovery nearly a century ago, a measurement of the excitonic wave function has remained beyond experimental reach. Here, we directly image the excitonic wave function in reciprocal space by measuring the momentum distribution of electrons photoemitted from excitons in monolayer tungsten diselenide. By transforming to real space, we obtain a visual of the distribution of the electron around the hole in an exciton. Further, by also resolving the energy coordinate, we confirm the elusive theoretical prediction that the photoemitted electron exhibits an inverted energy-momentum dispersion relationship reflecting the valence band where the partner hole remains, rather than that of conduction band states of the electron.

Dynamics of malaria drug resistance patterns in the Amazon basin region following changes in Peruvian national treatment policy for uncomplicated malaria.

Monitoring changes in the frequencies of drug-resistant and -sensitive genotypes can facilitate in vivo clinical trials to assess the efficacy of drugs before complete failure occurs. Peru changed its national treatment policy for uncomplicated malaria to artesunate (ART)-plus-mefloquine (MQ) combination therapy in the Amazon basin in 2001. We genotyped isolates collected in 1999 and isolates collected in 2006 to 2007 for mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, multidrug resistance gene 1 (Pfmdr-1), the chloroquine (CQ) resistance transporter gene (Pfcrt), and the Ca(2+) ATPase gene (PfATP6); these have been shown to be involved in resistance to sulfadoxine-pyrimethamine (SP), MQ, CQ, and possibly ART, respectively. Microsatellite haplotypes around the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr-1 loci were also determined. There was a significant decline in the highly SP resistant Pfdhfr and Pfdhps genotypes from 1999 to 2006. In contrast, a CQ-resistant Pfcrt genotype increased in frequency during the same period. Among five different Pfmdr-1 allelic forms noted in 1999, two genotypes increased in frequency while one genotype decreased by 2006. We also noted previously undescribed polymorphisms in the PfATP6 gene as well as an increase in the frequency of a deletion mutant during this period. In addition, microsatellite analysis revealed that the resistant Pfdhfr, Pfdhps, and Pfcrt genotypes have each evolved from a single founder haplotype, while Pfmdr-1 genotypes have evolved from at least two independent haplotypes. Importantly, this study demonstrates that the Peruvian triple mutant Pfdhps genotypes are very similar to those found in other parts of South America.

Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria.

BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ) have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS) combination therapy was adopted as the first-line treatment for uncomplicated Plasmodium falciparum malaria in the Amazon region of Peru. Although MQ resistance has yet to be reported from the Peruvian Amazon, it has been reported from other countries in the Amazon Region. Therefore, continuous monitoring is warranted to ensure that the first-line therapy remains efficacious. This study examines the in vivo efficacy and pharmacokinetic parameters through Day 56 of three commercial formulations of MQ (Lariam, Mephaquin, and Mefloquina-AC Farma) given in combination with artesunate. METHODS: Thirty-nine non-pregnant adults with P. falciparum mono-infection were randomly assigned to receive artesunate in combination with either (1) Lariam, (2) Mephaquin, or (3) Mefloquina AC. Patients were assessed on Day 0 (with blood samples for pharmacokinetics at 0, 2, 4, and 8 hours), 1, 2, 3, 7, and then weekly until day 56. Clinical and parasitological outcomes were based on the standardized WHO protocol.Whole blood mefloquine concentrations were determined by high-performance liquid chromatography and pharmacokinetic parameters were determined using non-compartmental analysis of concentration versus time data. RESULTS: By day 3, all patients had cleared parasitaemia except for one patient in the AC Farma arm; this patient cleared by day 4. No recurrences of parasitaemia were seen in any of the 34 patients. All three MQ formulations had a terminal half-life of 14-15 days and time to maximum plasma concentration of 45-52 hours. The maximal concentration (Cmax) and interquartile range was 2,820 ng/ml (2,614-3,108) for Lariam, 2,500 ng/ml (2,363-2,713) for Mephaquin, and 2,750 ng/ml (2,550-3,000) for Mefloquina AC Farma. The pharmacokinetics of the three formulations were generally similar, with the exception of the Cmax of Mephaquin which was significantly different to that of Lariam (p = 0.04). CONCLUSION: All three formulations had similar pharmacokinetics; in addition, the pharmacokinetics seen in this Peruvian population were similar to reports from other ethnic groups. All patients rapidly cleared their parasitaemia with no evidence of recrudescence by Day 56. Continued surveillance is needed to ensure that patients continue to receive optimal therapy.