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"Walters, T"
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The privatisation of biodiversity? : new approaches to conservation law
Current regulatory approaches have not prevented the loss of biodiversity across the world. This book explores the scope to strengthen conservation by using different legal mechanisms such as biodiversity offsetting, payment for ecosystem services and conservation covenants, as well as tradable development rights and taxation. The authors discuss how such mechanisms introduce elemhents of a market approach as well as private sector initiative and resources. They show how examples already in operation serve to highlight the design challenges, legal, technical and ethical, that must be overcome.
Book
Phenotype, function, and differentiation potential of human monocyte subsets
Human monocytes have been grouped into classical (CD14++CD16-), non-classical (CD14dimCD16++), and intermediate (CD14++CD16+) subsets. Documentation of normal function and variation in this complement of subtypes, particularly their differentiation potential to dendritic cells (DC) or macrophages, remains incomplete. We therefore phenotyped monocytes from peripheral blood of healthy subjects and performed functional studies on high-speed sorted subsets. Subset frequencies were found to be tightly controlled over time and across individuals. Subsets were distinct in their secretion of TNFα, IL-6, and IL-1β in response to TLR agonists, with classical monocytes being the most producers and non-classical monocytes the least. Monocytes, particularly those of the non-classical subtype, secreted interferon-α (IFN-α) in response to intracellular TLR3 stimulation. After incubation with IL-4 and GM-CSF, classical monocytes acquired monocyte-derived DC (mo-DC) markers and morphology and stimulated allogeneic T cell proliferation in MLR; intermediate and non-classical monocytes did not. After incubation with IL-3 and Flt3 ligand, no subset differentiated to plasmacytoid DC. After incubation with GM-CSF (M1 induction) or macrophage colony-stimulating factor (M-CSF) (M2 induction), all subsets acquired macrophage morphology, secreted macrophage-associated cytokines, and displayed enhanced phagocytosis. From these studies we conclude that classical monocytes are the principal source of mo-DCs, but all subsets can differentiate to macrophages. We also found that monocytes, in particular the non-classical subset, represent an alternate source of type I IFN secretion in response to virus-associated TLR agonists.
Journal Article
Virasoro conformal blocks and thermality from classical background fields
A
bstract
We show that in 2d CFTs at large central charge, the coupling of the stress tensor to heavy operators can be re-absorbed by placing the CFT in a non-trivial background metric. This leads to a more precise computation of the Virasoro conformal blocks between heavy and light operators, which are shown to be equivalent to global conformal blocks evaluated in the new background. We also generalize to the case where the operators carry U(1) charges. The refined Virasoro blocks can be used as the seed for a new Virasoro block recursion relation expanded in the heavy-light limit. We comment on the implications of our results for the universality of black hole thermality in AdS
3
, or equivalently, the eigenstate thermalization hypothesis for CFT
2
at large central charge.
Journal Article
Universality of long-distance AdS physics from the CFT bootstrap
A
bstract
We begin by explicating a recent proof of the cluster decomposition principle in AdS
≥4
from the CFT
≥3
bootstrap. The CFT argument also computes the leading interactions between distant objects in AdS
≥4
, and we confirm the universal agreement between the CFT bootstrap and AdS gravity in the semi-classical limit.
We proceed to study the generalization to CFT
2
, which requires knowledge of the Virasoro conformal blocks in a lightcone OPE limit. We compute these blocks in a semiclassical, large central charge approximation, and use them to prove a suitably modified theorem. In particular, from the
d
= 2 bootstrap we prove the existence of large spin operators with fixed ‘anomalous dimensions’ indicative of the presence of deficit angles in AdS
3
. As we approach the threshold for the BTZ black hole, interpreted as a CFT
2
scaling dimension, the twist spectrum of large spin operators becomes dense.
Due to the exchange of the Virasoro identity block, primary states above the BTZ threshold mimic a thermal background for light operators. We derive the BTZ quasinormal modes, and we use the bootstrap equation to prove that the twist spectrum is dense. Corrections to thermality could be obtained from a more refined computation of the Virasoro conformal blocks.
Journal Article
Genomic findings in schizophrenia and their implications
There has been substantial progress in understanding the genetics of schizophrenia over the past 15 years. This has revealed a highly polygenic condition with the majority of the currently explained heritability coming from common alleles of small effect but with additional contributions from rare copy number and coding variants. Many specific genes and loci have been implicated that provide a firm basis upon which mechanistic research can proceed. These point to disturbances in neuronal, and particularly synaptic, functions that are not confined to a small number of brain regions and circuits. Genetic findings have also revealed the nature of schizophrenia’s close relationship to other conditions, particularly bipolar disorder and childhood neurodevelopmental disorders, and provided an explanation for how common risk alleles persist in the population in the face of reduced fecundity. Current genomic approaches only potentially explain around 40% of heritability, but only a small proportion of this is attributable to robustly identified loci. The extreme polygenicity poses challenges for understanding biological mechanisms. The high degree of pleiotropy points to the need for more transdiagnostic research and the shortcomings of current diagnostic criteria as means of delineating biologically distinct strata. It also poses challenges for inferring causality in observational and experimental studies in both humans and model systems. Finally, the Eurocentric bias of genomic studies needs to be rectified to maximise benefits and ensure these are felt across diverse communities. Further advances are likely to come through the application of new and emerging technologies, such as whole-genome and long-read sequencing, to large and diverse samples. Substantive progress in biological understanding will require parallel advances in functional genomics and proteomics applied to the brain across developmental stages. For these efforts to succeed in identifying disease mechanisms and defining novel strata they will need to be combined with sufficiently granular phenotypic data.
Journal Article
Genetic identification of brain cell types underlying schizophrenia
With few exceptions, the marked advances in knowledge about the genetic basis of schizophrenia have not converged on findings that can be confidently used for precise experimental modeling. By applying knowledge of the cellular taxonomy of the brain from single-cell RNA sequencing, we evaluated whether the genomic loci implicated in schizophrenia map onto specific brain cell types. We found that the common-variant genomic results consistently mapped to pyramidal cells, medium spiny neurons (MSNs) and certain interneurons, but far less consistently to embryonic, progenitor or glial cells. These enrichments were due to sets of genes that were specifically expressed in each of these cell types. We also found that many of the diverse gene sets previously associated with schizophrenia (genes involved in synaptic function, those encoding mRNAs that interact with FMRP, antipsychotic targets, etc.) generally implicated the same brain cell types. Our results suggest a parsimonious explanation: the common-variant genetic results for schizophrenia point at a limited set of neurons, and the gene sets point to the same cells. The genetic risk associated with MSNs did not overlap with that of glutamatergic pyramidal cells and interneurons, suggesting that different cell types have biologically distinct roles in schizophrenia.
Integration of single-cell RNA sequencing with genome-wide association data implicates specific brain cell types in schizophrenia. Gene sets previously associated with schizophrenia implicate the same cell types, which include pyramidal cells and medium spiny neurons.
Journal Article
Analysis of copy number variations at 15 schizophrenia-associated loci
A number of copy number variants (CNVs) have been suggested as susceptibility factors for schizophrenia. For some of these the data remain equivocal, and the frequency in individuals with schizophrenia is uncertain.
To determine the contribution of CNVs at 15 schizophrenia-associated loci (a) using a large new data-set of patients with schizophrenia (n = 6882) and controls (n = 6316), and (b) combining our results with those from previous studies.
We used Illumina microarrays to analyse our data. Analyses were restricted to 520 766 probes common to all arrays used in the different data-sets.
We found higher rates in participants with schizophrenia than in controls for 13 of the 15 previously implicated CNVs. Six were nominally significantly associated (P<0.05) in this new data-set: deletions at 1q21.1, NRXN1, 15q11.2 and 22q11.2 and duplications at 16p11.2 and the Angelman/Prader-Willi Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were of maternal origin. When combined with published data, 11 of the 15 loci showed highly significant evidence for association with schizophrenia (P<4.1×10(-4)).
We strengthen the support for the majority of the previously implicated CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9% of controls carry a large, detectable CNV at one of these loci. Routine CNV screening may be clinically appropriate given the high rate of known deleterious mutations in the disorder and the comorbidity associated with these heritable mutations.
Journal Article
Thermalization and chaos in a 1+1d QFT
A
bstract
We study aspects of chaos and thermodynamics at strong coupling in a scalar model using LCT numerical methods. We find that our eigenstate spectrum satisfies Wigner-Dyson statistics and that the coefficients describing eigenstates in our basis satisfy Random Matrix Theory (RMT) statistics. At weak coupling, though the bulk of states satisfy RMT statistics, we find several scar states as well. We then use these chaotic states to compute the equation of state of the model, obtaining results consistent with Conformal Field Theory (CFT) expectations at temperatures above the scale of relevant interactions. We also test the Eigenstate Thermalization Hypothesis by computing the expectation value of local operators in eigenstates, and check that their behavior is consistent with thermal CFT values at high temperatures. Finally, we compute the Spectral Form Factor (SFF), which has the expected behavior associated with the equation of state at short times and chaos at long times. We also propose a new technique for extracting the connected part of the SFF without the need of disorder averaging by using different symmetry sectors.
Journal Article
Flux correlators and semiclassics
A
bstract
We consider correlators for the flux of energy and charge in the background of operators with large global U(1) charge in conformal field theory (CFT). It has recently been shown that the corresponding Euclidean correlators generically admit a semiclassical description in terms of the effective field theory (EFT) for a conformal superfluid. We adapt the semiclassical description to Lorentzian observables and compute the leading large charge behavior of the flux correlators in general U(1) symmetric CFTs. We discuss the regime of validity of the large charge EFT for these Lorentzian observables and the subtleties in extending the EFT approach to subleading corrections. We also consider the Wilson-Fisher fixed point in
d
= 4 −
ϵ
dimensions, which offers a specific weakly coupled realization of the general setup, where the subleading corrections can be systematically computed without relying on an EFT.
Journal Article
Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations
People with schizophrenia are enriched for rare coding variants in genes associated with neurodevelopmental disorders, particularly autism spectrum disorders and intellectual disability. However, it is unclear if the same changes to gene function that increase risk to neurodevelopmental disorders also do so for schizophrenia. Using data from 3444 schizophrenia trios and 37,488 neurodevelopmental disorder trios, we show that within shared risk genes, de novo variants in schizophrenia and neurodevelopmental disorders are generally of the same functional category, and that specific de novo variants observed in neurodevelopmental disorders are enriched in schizophrenia (
P
= 5.0 × 10
−6
). The latter includes variants known to be pathogenic for syndromic disorders, suggesting that schizophrenia be included as a characteristic of those syndromes. Our findings imply that, in part, neurodevelopmental disorders and schizophrenia have shared molecular aetiology, and therefore likely overlapping pathophysiology, and support the hypothesis that at least some forms of schizophrenia lie on a continuum of neurodevelopmental disorders.
Overlapping genes have been implicated in schizophrenia and neurodevelopmental disorders. Here, the authors overlap de novo variants in the two types of disorders and find variants in these genes with the same functional effect and in some cases the same specific variants.
Journal Article