Effective Actions for Massive Kaluza-Klein States on AdS_3 x S^3 x S^3

We construct the effective supergravity actions for the lowest massive Kaluza-Klein states on the supersymmetric background AdS_3 x S^3 x S^3. In particular, we describe the coupling of the supergravity multiplet to the lowest massive spin-3/2 multiplet which contains 256 physical degrees of freedom and includes the moduli of the theory. The effective theory is realized as the broken phase of a particular gauging of the maximal three-dimensional supergravity with gauge group SO(4) x SO(4). Its ground state breaks half of the supersymmetries leading to 8 massive gravitinos acquiring mass in a super Higgs effect. The holographic boundary theory realizes the large N=(4,4) superconformal symmetry.Comment: 31 pages, v2: minor change

Phasing of dragonfly wings can improve aerodynamic efficiency by removing swirl

Dragonflies are dramatic, successful aerial predators, notable for their flight agility and endurance. Further, they are highly capable of low-speed, hovering and even backwards flight. While insects have repeatedly modified or reduced one pair of wings, or mechanically coupled their fore and hind wings, dragonflies and damselflies have maintained their distinctive, independently controllable, four-winged form for over 300 Myr. Despite efforts at understanding the implications of flapping flight with two pairs of wings, previous studies have generally painted a rather disappointing picture: interaction between fore and hind wings reduces the lift compared with two pairs of wings operating in isolation. Here, we demonstrate with a mechanical model dragonfly that, despite presenting no advantage in terms of lift, flying with two pairs of wings can be highly effective at improving aerodynamic efficiency. This is achieved by recovering energy from the wake wasted as swirl in a manner analogous to coaxial contra-rotating helicopter rotors. With the appropriate fore–hind wing phasing, aerodynamic power requirements can be reduced up to 22 per cent compared with a single pair of wings, indicating one advantage of four-winged flying that may apply to both dragonflies and, in the future, biomimetic micro air vehicles

Next-generation sequencing-based genome diagnostics across clinical genetics centers: Implementation choices and their effects

Implementation of next-generation DNA sequencing (NGS) technology into routine diagnostic genome care requires strategic choices. Instead of theoretical discussions on the consequences of such choices, we compared NGS-based diagnostic practices in eight clinical genetic centers in the Netherlands, based on genetic testing of nine pre-selected patients with cardiomyopathy. We highlight critical implementation choices, including the specific contributions of laboratory and medical specialists, bioinformaticians and researchers to diagnostic genome care, and how these affect interpretation and reporting of variants. Reported pathogenic mutations were consistent for all but one patient. Of the two centers that were inconsistent in their diagnosis, one reported to have found 'no causal variant', thereby underdiagnosing this patient. The other provided an alternative diagnosis, identifying another variant as causal than the other centers. Ethical and legal analysis showed that informed consent procedures in all centers were generally adequate for diagnostic NGS applications that target a limited set of genes, but not for exome- and genome-based diagnosis. We propose changes to further improve and align these procedures, taking into account the blurring boundary between diagnostics and research, and specific counseling options for exome- and genome-based diagnostics. We conclude that alternative diagnoses may infer a certain level of 'greediness' to come to a positive diagnosis in interpreting sequencing results. Moreover, there is an increasing interdependence of clinic, diagnostics and research departments for comprehensive diagnostic genome care. Therefore, we invite clinical geneticists, physicians, researchers, bioinformatics experts and patients to reconsider their role and position in future diagnostic genome care

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies