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While genome-wide association studies (GWAS) and selection scans identify genomic loci driving human phenotypic diversity, functional validation is required to discover the variant(s) responsible. We dissected theIVDlocus, implicated by selection statistics, multiple GWAS, and clinical genetics as important to function and fitness. We combined luciferase assays, CRISPR/Cas9 genome-editing, massively parallel reporter assays (MPRA), and bashing of regulatory loci. We identified three regulatory variants, including an indel, that may underpin GWAS signals for pulmonary fibrosis and testosterone, and that are linked on a positively selected haplotype in the Japanese population. These regulatory variants exhibit synergistic and opposing effects onIVDexpression experimentally. Alleles at these variants lie on a haplotype tagged by the variant most strongly associated withIVDexpression and metabolites, but with no functional evidence itself. This work demonstrates how comprehensive functional investigation and multiple technologies are needed to discover the true genetic drivers of phenotypic diversity.

Unmanned aerial vehicles, otherwise known as drones, are one of the most important developments in global security in the 21st century. Drones, which can be operated remotely from ground pilots, are now in use by more than 100 countries and a growing number of non-state actors, such as terrorist groups. Some of this is driven by a booming export market in drones, with countries such as the United States, Israel, China, and Turkey becoming the world’s leading suppliers of the technology. Drones have begun to alter the course of conventional wars, as seen in Nagorno-Karabakh and Ukraine, and also have enabled new practices such as targeted killings of terrorist operatives either on their own territory or, in the case of the United States, on remote battlefields. Drones are also shifting how states attempt to deter and coerce each other and also enabling non-state actors such as terrorist groups to strike at opponents in new and surprising ways. As drones have begun to affect the security of individuals, non-state actors, and states, they have also yielded a number of legal and ethical controversies about when and where they should be used. In particular, the remote nature of the technology raises questions as to whether the distance of their pilots from the battlefields that they fight on is producing the “push-button warfare” mentality or otherwise lowering the barriers to the use of force. Future trends in the technological development of drone warfare, including swarming and the use of artificial intelligence–enabled drones, will only make coming to grips with the impact of drones on global security more important.

International audience; Wetting of polymer-grafted nanoparticles (NPs) in a polymer nanocomposite (PNC) film is driven by a difference in surface energy between components as well as bulk thermodynamics, namely, the value of the interaction parameter, χ. The interplay between these contributions is investigated in a PNC containing 25 wt % polymethyl methacrylate (PMMA)-grafted silica NPs (PMMA-NPs) in poly(styrene-ran-acrylonitrile) (SAN) upon annealing above the lower critical solution temperature (LCST, 160 °C). Atomic force microscopy (AFM) studies show that the areal density of particles increases rapidly and then approaches 80% of that expected for random close-packed hard spheres. A slightly greater areal density is observed at 190 °C compared to 170 °C. The PMMA-NPs are also shown to prevent dewetting of PNC films under conditions where the analogous polymer blend is unstable. Transmission electron microscopy (TEM) imaging shows that PMMANPs symmetrically wet both interfaces and form columns that span the free surface and substrate interface. Using grazingincidence Rutherford backscattering spectrometry (GI-RBS), the PMMA-NP surface excess (Z*) initially increases rapidly with time and then approaches a constant value at longer times. Consistent with the areal density, Z* is slightly greater at deeper quench depths, which is attributed to the more unfavorable interactions between the PMMA brush and SAN segments. The Z* values at early times are used to determine the PMMA-NP diffusion coefficients, which are significantly larger than theoretical predictions. These studies provide insights into the interplay between wetting and phase separation in PNCs and can be utilized in nanotechnology applications where surface-dependent properties, such as wettability, durability, and friction, are important.

The performance of DNA metabarcoding approaches for characterizing biodiversity can be influenced by multiple factors. Here, we used morphological assessment of taxa in zooplankton samples to develop a large barcode database and to assess the congruence of taxonomic identification with metabarcoding under different conditions. We analysed taxonomic assignment of metabarcoded samples using two genetic markers (COI, 18S V1–2), two types of clustering into molecular operational taxonomic units (OTUs, ZOTUs), and three methods for taxonomic assignment (RDP Classifier, BLASTn to GenBank, BLASTn to a local barcode database). The local database includes 1042 COI and 1108 18S (SSU) barcode sequences, and we added new high-quality sequences to GenBank for both markers, including 109 contributions at the species level. The number of phyla detected and the number of taxa identified to phylum varied between a genetic marker and among the three methods used for taxonomic assignments. Blasting the metabarcodes to the local database generated multiple unique contributions to identify OTUs and ZOTUs. We argue that a multi-marker approach combined with taxonomic expertise to develop a curated, vouchered, local barcode database increases taxon detection with metabarcoding, and its potential as a tool for zooplankton biodiversity surveys.

Biodiversity assessments are critical for setting conservation priorities, understanding ecosystem function and establishing a baseline to monitor change. Surveys of marine biodiversity that rely almost entirely on sampling adult organisms underestimate diversity because they tend to be limited to habitat types and individuals that can be easily surveyed. Many marine animals have planktonic larvae that can be sampled from the water column at shallow depths. This life stage often is overlooked in surveys but can be used to relatively rapidly document diversity, especially for the many species that are rare or live cryptically as adults. Using DNA barcode data from samples of nemertean worms collected in three biogeographical regions—Northeastern Pacific, the Caribbean Sea and Eastern Tropical Pacific—we found that most species were collected as either benthic adults or planktonic larvae but seldom in both stages. Randomization tests show that this deficit of operational taxonomic units collected as both adults and larvae is extremely unlikely if larvae and adults were drawn from the same pool of species. This effect persists even in well-studied faunas. These results suggest that sampling planktonic larvae offers access to a different subset of species and thus significantly increases estimates of biodiversity compared to sampling adults alone. Spanish abstract is available in the electronic supplementary material.

The US will not be able to manage a long-term ideological struggle unless it addresses illiberalism in its own political institutions.

Under what circumstances do armed groups in conflict choose to use terrorist bombings? This article challenges the conventional wisdom that terrorist bombings are done by either ideologically-drive...

Why does the United States seek to export its own political and economic system as part of an intervention? We argue that the U.S. has an ideologically-inflected strategic culture which has yielded two ‘ways’ of intervention over time. The limited model is cost conscious and cedes control over the future of the state to local actors provided that they guarantee open markets and good government. The vindicationist model involves the U.S. paying costs to remake another society in its own image. We argue that the vindicationist way of intervention is activated at moments of strategic surprise, which cause policymakers to react by gambling on large interventions to remake another society. To empirically demonstrate the validity of this explanation, we examine the record of America of limited and vindicationist major interventions from 1946-2005 and present two contrasting case studies of Cold War interventions in Lebanon and the Dominican Republic. Postprint

The identity of wild cloning sea star larvae has been a mystery since they were first documented in the Caribbean. The most commonly collected cloning species was thought to belong to the Oreasteridae, on the basis of similarity with sequences from

This book explores how the unique features of drone technology alter the strategic choices of governments and non-state actors alike by transforming their risk calculations and expanding their goals on and off the battlefield. It considers how drone technology will impact the patterns of war and peace in the next century: Will drones produce a more peaceful world because they reduce risk to pilots, or will the prospect of clean, remote warfare lead governments to engage in more conflicts? Will drones begin to replace humans on the battlefield or will they empower soldiers and peacekeepers to act more precisely and humanely in crisis zones? How will terrorist organizations turn this technology back on the governments that fight them? How will drones change surveillance at war—and at home? As drones come into the hands of new actors—foreign governments, law enforcement, terrorist organizations, humanitarian organizations, and even UN peacekeepers—it is even more important to understand what kind of world they might produce. By changing what these actors are both willing and able to do, drones are quietly altering the dynamics of wars, humanitarian crises, and peacekeeping missions, while generating new risks to security and privacy. An essential guide to a potentially disruptive force in modern world politics, The Drone Age argues that the mastery of drone technology will become central to the ways that governments and non-state actors seek power and influence in the coming decades.

Chapter 4 argues that drones accelerate the trend toward information-rich warfare and place enormous pressure on the military to learn ever more about the battlefields that it faces. Today, for the United States, war is increasingly a contest for information about any future battlespace. This has had an organizational effect as the ability for the United States to know more through drone imagery has turned into a necessity to know more. The US military is becoming so enamored of its ability to know more through drone surveillance that it is overlooking the operational and organizational costs of “collecting the whole haystack.” Using drones for a vast surveillance apparatus, as the United States and now other countries have been doing, has underappreciated implications for the workload, organizational structures, and culture of the military itself.

In chapter 6, drones are described as transforming the dynamics of protest and surveillance in democratic and non-democratic states. The use of drones by law enforcement and private companies poses a serious challenge to the protection of privacy and could contribute to a creeping surveillance state. But drones will also empower other groups—civil liberties groups and activists—to identify and publicize human rights abuses and press democratic governments to act. In authoritarian states, the embrace of drone technology also raises the possibility that anonymous dissent may eventually become difficult, if not impossible. Drones may also provide another tool for governments to engage in surveillance and repression of their secessionist regions.

Chapter 3 argues that drones undermine the legal and ethical prohibitions on assassination and extrajudicial violence outside of wartime. It traces the emergence of the practice of targeted killing from its origin to its embrace by the United States after the September 11 attacks. It shows how the United States adopted the use of drones alongside the practice of targeted killing to control risks as it fought a new war against al Qaeda, but found itself gradually drifting into more conflict zones and fighting new enemies. While the United States used drones to protect its pilots from physical risk, it altered the nature of the risks they faced and created new ones for the population who live under the drones. Drones also subtly changed how the United States wages its wars, making it more willing to countenance killing people outside of active battlefields. It concludes by discussing how more countries are now experimenting with targeting killings.

Chapter 8 suggests that drones will amplify the competition for power and influence between states in conflict zones and produce new risks of deterrence breakdown and crisis escalation. It shows how states are already using drone technology to test the nerves and strategic commitments of their rivals, as well as to conduct surveillance that would otherwise been seen as too risky in crisis zones. This is because drones have changed risk calculations; what was once too dangerous with a manned aircraft is now possible with a drone. These strategic gambits are possible because of their low financial and human costs, as well as the illusion that drones can be used without the risk of escalation. As drones are now being used in more conflict zones around the world, they will begin to quietly reorder the risk calculations behind deterrence and coercion and produce greater chances of miscalculation, error, and accident.

Chapter 7 argues that drones will enable international organizations, NGOs, and advocacy groups to monitor human rights abuses, deliver relief, and pressure governments for change. Small surveillance drones are ideally suited for taking on the “dull, dirty, and dangerous” jobs that are needed in these situations. In the future, drones will be able to transport and drop food and medicine in response to crises in places where humanitarian organizations are reluctant to send their own personnel. Drones will ultimately give these actors another tool with which they can monitor events on the ground and possibly shame governments into stronger action. But drones may also increase the ambitions of IOs/NGOs to intensify the pace of humanitarian relief and social change, even if doing so is unsustainable.

Chapter 9 restates the major theme of the book: that drones change strategic choices for their users by altering their calculation of risks and expanding their goals. It notes that while drones have many peacetime and humanitarian uses, it is their destructive potential that haunts the general public. The apparent absence of risk when using drones in conflict zones changes the choices and behavior of users. It concludes that drones cannot be considered as politically neutral, but rather as irreducibly political and inclined to privilege specific modes of action and thinking. It also identifies future trends that might intersect with drone technology, including the rise of AI, autonomy, swarming, miniaturization and others.

Chapter 5 argues that drones will allow non-state actors like rebel and terrorist groups to begin to level the playing field with powerful governments and to expand their goals as a result of being able to take to the skies. The low marginal cost of drones will be a boon to non-state actors who will use them to blunt the advantages that governments currently enjoy. In conflict zones, drones enable groups like Hezbollah and the Islamic State to watch the battlefield in a way that they never could before and to strike at their enemies in surprising ways. At home, drones will enable terrorist organizations to strike civilian targets and perhaps even assassinate world leaders.

Historians may well conclude that Obama glimpsed a different world for American foreign policy but never exerted the kind of strategic direction needed to turn that vision into reality.

The diversity of tropical marine invertebrates is poorly documented, especially those groups for which collecting adults is difficult. We collected the planktonic tornaria larvae of hemichordates (acorn worms) to assess their hidden diversity in the Neotropics. Larvae were retrieved in plankton tows from waters of the Pacific and Caribbean coasts of Panama, followed by DNA barcoding of mitochondrial cytochrome c oxidase subunit I (COI) and 16S ribosomal DNA to estimate their diversity in the region. With moderate sampling efforts, we discovered six operational taxonomic units (OTUs) in the Bay of Panama on the Pacific coast, in contrast to the single species previously recorded for the entire Tropical Eastern Pacific. We found eight OTUs in Bocas del Toro province on the Caribbean coast, compared to seven species documented from adults in the entire Caribbean. All OTUs differed from each other and from named acorn worm sequences in GenBank by >10% pairwise distance in COI and >2% in 16S. Two of our OTUs matched 16S hemichordate sequences in GenBank: one was an unidentified or unnamed Balanoglossus from the Caribbean of Panama, and the other was an unidentified ptychoderid larva from the Bahamas. The species accumulation curves suggest that nearly all the species have been collected and only one more species might still remain undetected in the Pacific. In contrast, the Caribbean species accumulation curve suggests that further sampling could yield more than 10 additional OTUs. Tornaria from the 14 OTUs exhibited typical planktotrophic morphologies, and, in some cases, may be distinguished by differences in pigmentation and by the number of telotrochal ciliary bands, but in general, few diagnostic differences were detected.

Sipuncula is a clade of unsegmented marine worms that are currently placed among the basal radiation of conspicuously segmented Annelida. Their new location provides a unique opportunity to reinvestigate the evolution and development of segmented body plans. Neural segmentation is clearly evident during ganglionic ventral nerve cord (VNC) formation across Sedentaria and Errantia, which includes the majority of annelids. However, recent studies show that some annelid taxa outside of Sedentaria and Errantia have a medullary cord, without ganglia, as adults. Importantly, neural development in these taxa is understudied and interpretation can vary widely. For example, reports in sipunculans range from no evidence of segmentation to vestigial segmentation as inferred from a few pairs of serially repeated neuronal cell bodies along the VNC. We investigated patterns of pan-neuronal, neuronal subtype, and axonal markers using immunohistochemistry and whole mount in situ hybridization (WMISH) during neural development in an indirect-developing sipunculan, Themiste lageniformis. Confocal imaging revealed two clusters of 5HT+ neurons, two pairs of FMRF+ neurons, and Tubulin+ peripheral neurites that appear to be serially positioned along the VNC, similar to other sipunculans, to other annelids, and to spiralian taxa outside of Annelida. WMISH of a synaptotagmin1 ortholog in T. lageniformis (Tl-syt1) showed expression throughout the centralized nervous system (CNS), including the VNC where it appears to correlate with mature 5HT+ and FMRF+ neurons. An ortholog of elav1 (Tl-elav1) showed expression in differentiated neurons of the CNS with continuous expression in the VNC, supporting evidence of a medullary cord, and refuting evidence of ontogenetic segmentation during formation of the nervous system. Thus, we conclude that sipunculans do not exhibit any signs of morphological segmentation during development.

This conclusion draws out the chief findings from a comparative analysis of the preceding chapters. It also offers policy implications, specifically highlighting how policymakers in Western countries can be culturally sensitive to the different conceptualizations of terrorism present elsewhere and tailor their requests for cooperation accordingly.

This introduction chapter identifies the rationale for a comparative study of the counterterrorism responses of non-Western states. It argues that much of the counterterrorism literature is biased towards Western perspectives, particularly that of the United States, United Kingdom, and Israel, and tends to ignore the distinct counterterrorism approaches of non-Western states. This chapter defines what is meant by “non-Western” in this volume and identifies the drivers – historical, social, political, cultural and religious – that determine their counterterrorism response.

Background The Scalidophora (Kinorhyncha, Loricifera and Priapulida) have an important phylogenetic position as early branching ecdysozoans, yet the architecture of their nervous organ systems is notably underinvestigated. Without such information, and in the absence of a stable phylogenetic context, we are inhibited from producing adequate hypotheses about the evolution and diversification of ecdysozoan nervous systems. Here, we utilize confocal laser scanning microscopy to characterize serotonergic, tubulinergic and FMRFamidergic immunoreactivity patterns in a comparative neuroanatomical study with three species of Echinoderes, the most speciose, abundant and diverse genus within Kinorhyncha. Results Neuroanatomy in Echinoderes as revealed by acetylated α-tubulin immunoreactivity includes a circumpharyngeal brain and ten neurite bundles in the head region that converge into five longitudinal nerves within the trunk. The ventral nerve cord is ganglionated, emerging from the brain with two connectives that converge in trunk segments 2–3, and diverge again within segment 8. The longitudinal nerves and ventral nerve cord are connected by two transverse neurites in segments 2–9. Differences among species correlate with the number, position and innervation of cuticular structures along the body. Patterns of serotoninergic and FMRFamidergic immunoreactivity correlate with the position of the brain neuropil and the ventral nerve cord. Distinct serotonergic and FMRFamidergic somata are associated with the brain neuropil and specific trunk segments along the ventral nerve cord. Conclusions Neural architecture is highly conserved across all three species, suggesting that our results reveal a pattern that is common to more than 40% of the species within Kinorhyncha. The nervous system of Echinoderes is segmented along most of the trunk; however, posterior trunk segments exhibit modifications that are likely associated with sensorial, motor or reproductive functions. Although all kinorhynchs show some evidence of an externally segmented trunk, it is unclear whether external segmentation matches internal segmentation of nervous and muscular organ systems across Kinorhyncha, as we observed in Echinoderes. The neuroanatomical data provided in this study not only expand the limited knowledge on kinorhynch nervous systems but also establish a comparative morphological framework within Scalidophora that will support broader inferences about the evolution of neural architecture among the deepest branching lineages of the Ecdysozoa. Electronic supplementary material The online version of this article (10.1186/s12862-019-1405-4) contains supplementary material, which is available to authorized users.

The new international order will be marked by the ascendancy of illiberal states and value systems, and a diminishment of American influence.

Recent advances in optical microscopy instrumentation and processing techniques have led to imaging that both breaks the diffraction barrier and enables sub-pixel resolution. This enhanced resolution has expanded the capabilities of particle tracking to nanoscale processes in soft matter including biomolecular, colloidal, and polymeric materials. This tutorial provides a basic understanding of particle tracking instrumentation, the fundamentals of tracking analysis, and potential sources of error and bias inherent in analyzing particle tracking. Finally, we provide a brief outlook for the future of particle tracking through the lens of machine learning.

Military forces are an indispensable complement to law enforcement and bring with them a number of organizational resources that are crucial to dealing with terrorism. The division of labour between police and military for counterterrorism functions is best conceptualized as a continuum rather than a chasm, with many counterterrorism organizations falling in between. The longstanding debate over the military dimension to counterterrorism has been transformed due to two developments. They are the growing popularity of counterinsurgency as a model for destroying terrorist groups in ungoverned spaces; and the rise of a light footprint approach, based on new technology like drones, which appear to give governments the opportunity to be discriminate, even surgical, in their air strikes against terrorist groups abroad with a costly occupation. The first major development that has transformed the military's role in counterterrorism has been the rise of counterinsurgency (COIN) as a way of dealing with terrorist groups.