Asymptotically Optimal Tests for Single-Index Restrictions with a Focus on Average Partial Effects

This paper proposes an asymptotically optimal specification test of single-index models against alternatives that lead to inconsistent estimates of a covariate’s average partial effect. The proposed tests are relevant when a researcher is concerned about a potential violation of the single-index restriction only to the extent that the estimated average partial effects suffer from a nontrivial bias due to the misspecifcation. Using a pseudo-norm of average partial effects deviation and drawing on the minimax approach, we find a nice characterization of the least favorable local alternatives associated with misspecified average partial effects as a single direction of Pitman local alternatives. Based on this characterization, we define an asymptotic optimal test to be a semiparametrically efficient test that tests the significance of the least favorable direction in an augmented regression formulation, and propose such a one that is asymptotically distribution-free, with asymptotic critical values available from the X 2/1 table. The testing procedure can be easily modified when one wants to consider average partial effects with respect to binary covariates or multivariate average partial effects.Average Partial Effects, Omnibus tests, Optimal tests, Semi- parametric Efficiency, Efficient Score

Observables and Microscopic Entropy of Higher Spin Black Holes

In the context of recently proposed holographic dualities between higher spin theories in AdS3 and 1+1-dimensional CFTs with W-symmetry algebras, we revisit the definition of higher spin black hole thermodynamics and the dictionary between bulk fields and dual CFT operators. We build a canonical formalism based on three ingredients: a gauge-invariant definition of conserved charges and chemical potentials in the presence of higher spin black holes, a canonical definition of entropy in the bulk, and a bulk-to-boundary dictionary aligned with the asymptotic symmetry algebra. We show that our canonical formalism shares the same formal structure as the so-called holomorphic formalism, but differs in the definition of charges and chemical potentials and in the bulk-to-boundary dictionary. Most importantly, we show that it admits a consistent CFT interpretation. We discuss the spin-2 and spin-3 cases in detail and generalize our construction to theories based on the hs[\lambda] algebra, and on the sl(N,R) algebra for any choice of sl(2,R) embedding.Comment: 47 pages, references added, published versio

Lung epithelial cell differentiation in human and mouse:Environment, epigenetics and epigenetic editing

Roken tijdens de zwangerschap verhoogt het risico op ontwikkeling van astma op de kinderleeftijd. Daarnaast lijkt roken tijdens de zwangerschap een risicofactor te zijn voor ontwikkeling van de chronische rook-gerelateerde longziekte COPD (chronisch obstructieve longziekte), later in het leven. Dit suggereert dat de kiem voor het ontstaan van COPD op volwassen leeftijd al gelegd kan worden tijdens de ontwikkeling in de baarmoeder. Risicofactoren op een bepaalde ziekte kunnen erfelijk zijn en liggen dan vast in ons erfelijk materiaal, ons DNA. Daarnaast kunnen ook tijdens het leven veranderingen optreden in het gebruik van het DNA, zogenaamde epigenetische veranderingen. Epigenetische mechanismen zoals veranderingen in DNA methylatie en modificaties van het DNA-bindende eiwit histon zouden daaraan ten grondslag kunnen liggen. UMCG-promovendus Juan Song onderzocht de schadelijke effecten van roken tijdens de zwangerschap in een muizenmodel voor COPD. Nakomelingen van moeders die aan rook waren blootgesteld tijdens de zwangerschap hadden een verstoorde longontwikkeling en een verhoogde expressie van het gen SPDEF dat belangrijk is voor slijmcel ontwikkeling en slijmproductie in de long. Dit gen bleek ook verhoogd tot expressie te komen in longcellen van mensen met COPD. Verhoogde expressie van SPDEF en slijmproductie ging gepaard met een verlaagde DNA methylatie in het SPDEF gen. Hiermee bleek SPDEF een goede kandidaat te zijn voor een epigenetische therapeutische benadering waarmee een gen ‘aan’ of ‘uit’ gezet kan worden. Deze techniek wordt wel ‘Epigenetische Editing’ genoemd. In een longcellijn kon SPDEF succesvol uitgeschakeld worden en slijmproductie geremd worden met behulp van gen-specifieke DNA bindende eiwitten die gefuseerd waren aan transcriptieregulerende eiwitten. Dit veelbelovende resultaat is een eerste stap en opent perspectieven voor het moduleren van expressie van ieder gewenst gen voor de toekomst. Verder onderzoek moet echter eerst de specificiteit en de duurzaamheid van de epigenetische modulatie vaststellen, met het uiteindelijke doel om blijvende herprogrammering (bijvoorbeeld slijmreductie) in het organisme te bewerkstelligen.Smoking during pregnancy increases the risk of developing asthma in childhood. In addition, smoking during pregnancy seems to be a risk factor for development of the chronic smoking-related lung disease COPD (chronic obstructive pulmonary disease) later in life. This suggests that the origin of development of COPD in adulthood can already start during fetal development in the uterus. Risk factors for a particular disease can be hereditary and are then fixed in our genetic material, our DNA. In addition, also during life, changes occur in the use of the DNA. These are so-called epigenetic changes. Epigenetic mechanisms such as DNA methylation and modifications of the DNA-binding protein histone could be underlying these.UMCG researcher Juan Song examined the harmful effects of smoking during pregnancy in a mouse model for COPD. Offspring of mothers who had been exposed to smoke during pregnancy had an impaired lung development and an increased expression of the gene SPDEF that is important for epithelial cell development and mucus production in the lung. This gene was also found to be more expressed in lung cells of people with COPD. Increased expression of SPDEF and mucus production was accompanied by reduced DNA methylation in the SPDEF gene. This SPDEF proved to be a good candidate for an epigenetic therapeutic approach by which a gene can be switched 'on' or 'off'. This technique is called ‘Epigenetic Editing'. In a lung cell line, SPDEF could be successfully turned off and mucus production was inhibited by using gene-specific DNA binding proteins, which were fused to transcription regulatory proteins. This promising result is a first step, and opens up perspectives for modulating expression of any desired gene for the future. Further research, however, must first determine the specificity and the sustainability of the epigenetic modulation, with the ultimate goal to achieve lasting reprogramming (for instance mucus reduction) in the organism