Nonstationary-Volatility Robust Panel Unit Root Tests and the Great Moderation

This paper argues that typical applications of panel unit root tests should take possible nonstationarity in the volatility process of the innovations of the panel time series into account. Nonstationarity volatility arises for instance when there are structural breaks in the innovation variances. A prominent example is the reduction in GDP growth variances enjoyed by many industrialized countries, known as the 'Great Moderation'. It also proposes a new testing approach for panel unit roots that is, unlike many previously suggested tests, robust to such volatility processes. The panel test is based on Simes' (1986) classical multiple test, which combines evidence from time series unit root tests of the series in the panel. As time series unit root tests, we employ recently proposed tests of Cavaliere and Taylor (2008b). The panel test is robust to general patterns of cross-sectional dependence and yet is straightforward to implement, only requiring valid p-values of time series unit root tests, and no resampling. Monte Carlo experiments show that other panel unit root tests suffer from sometimes severe size distortions in the presence of nonstationary volatility, and that this defect can be remedied using the test proposed here. We use the methods developed here to test for unit roots in OECD panels of gross domestic products and infl ation rates, yielding inference robust to the 'Great Moderation'. We fi nd little evidence of trend stationarity, and mixed evidence regarding inflation stationarity.Die vorliegende Arbeit argumentiert, dass typische Anwendungen von Panel-Einheitswurzeltests die Möglichkeit von Nicht-Stationarität in dem Volatilitätsprozess der Innovationen der Panel-Zeitreihen berücksichtigen sollten. Nicht-stationäre Volatilität entsteht z.B. durch Strukturbrüche in den Varianzen der Innovationen. Ein prominentes Beispiel hierfür ist die Verringerung der Varianzen des BIP-Wachstums vieler Industrieländern, welche unter dem Begriff 'Great Moderation' bekannt ist. Außerdem schlägt die Arbeit einen neuen Testansatz für Panel-Einheitswurzeln vor, der im Gegensatz zu vielen zuvor vorgeschlagen Test robust ist gegenüber solchen Volatilitätsprozessen. Der Panel-Test basiert auf Simes' (1986) klassischem multiplen Testverfahren, welches auf einer Kombination von Zeitreihen-Einheitswurzeltests basiert. Als Zeitreihen-Einheitswurzeltest werden hier die kürzlich vorgeschlagenen Tests von Cavaliere und Taylor (2008b) verwendet. Der Panel-Test ist ebenfalls robust gegenüber allgemeinen Querschnittsabhängigkeitsstrukturen und ist einfach zu implementieren, da lediglich gültig p-Werte von Zeitreihen-Einheitswurzeltests erforderlich sind. Monte Carlo Experimente zeigen, dass andere Panel-Einheitswurzeltests bei Präsenz von nicht-stationärer Volatilität häufig unter starken Verzerrungen leiden, und dass dieser Mangel mit Hilfe des hier vorgeschlagen Verfahrens behoben werden kann. Diese Methode wird hier genutzt, um auf das Vorliegen von Einheitswurzeln in Panels der Bruttoinlandsprodukte und der Inflationsraten von OECD-Ländern zu testen. Dabei werden kaum Anzeichen für Trendstationarität und gemischte Evidenz für Inflations-Stationarität gefunden

On Unit Root Testing with Smooth Transitions

Improved critical values are calculated for Dickey-Fuller-type t ratio unit root tests against trend stationarity about non-linear trend, which is based on one deterministic smooth transition function. Simulation employs finegrid-searchoverbothsmoothtransitionparameterstofind accurate staring values, as well as constrained optimization. In addition, two new parsimonious models are introduced. Finally, an application of the test to the log of Real per capita GNP of USA is provided

Proteasome dysfunction induces excessive proteome instability and loss of mitostasis that can be mitigated by enhancing mitochondrial fusion or autophagy

The ubiquitin-proteasome pathway (UPP) is central to proteostasis network (PN) functionality and proteome quality control. Yet, the functional implication of the UPP in tissue homeodynamics at the whole organism level and its potential cross-talk with other proteostatic or mitostatic modules are not well understood. We show here that knock down (KD) of proteasome subunits in Drosophila flies, induced, for most subunits, developmental lethality. Ubiquitous or tissue specific proteasome dysfunction triggered systemic proteome instability and activation of PN modules, including macroautophagy/autophagy, molecular chaperones and the antioxidant cncC (the fly ortholog of NFE2L2/Nrf2) pathway. Also, proteasome KD increased genomic instability, altered metabolic pathways and severely disrupted mitochondrial functionality, triggering a cncC-dependent upregulation of mitostatic genes and enhanced rates of mitophagy. Whereas, overexpression of key regulators of antioxidant responses (e.g., cncC or foxo) could not suppress the deleterious effects of proteasome dysfunction; these were alleviated in both larvae and adult flies by modulating mitochondrial dynamics towards increased fusion or by enhancing autophagy. Our findings reveal the extensive functional wiring of genomic, proteostatic and mitostatic modules in higher metazoans. Also, they support the notion that age-related increase of proteotoxic stress due to decreased UPP activity deregulates all aspects of cellular functionality being thus a driving force for most age-related diseases. Abbreviations: ALP: autophagy-lysosome pathway; ARE: antioxidant response element; Atg8a: autophagy-related 8a; ATPsynβ: ATP synthase, β subunit; C-L: caspase-like proteasomal activity; cncC: cap-n-collar isoform-C; CT-L: chymotrypsin-like proteasomal activity; Drp1: dynamin related protein 1; ER: endoplasmic reticulum; foxo: forkhead box, sub-group O; GLU: glucose; GFP: green fluorescent protein; GLY: glycogen; Hsf: heat shock factor; Hsp: Heat shock protein; Keap1: kelch-like ECH-associated protein 1; Marf: mitochondrial assembly regulatory factor; NFE2L2/Nrf2: nuclear factor, erythroid 2 like 2; Opa1: optic atrophy 1; PN: proteostasis network; RNAi: RNA interference; ROS: reactive oxygen species; ref(2)P: refractory to sigma P; SQSTM1: sequestosome 1; SdhA: succinate dehydrogenase, subunit A; T-L: trypsin-like proteasomal activity; TREH: trehalose; UAS: upstream activation sequence; Ub: ubiquitin; UPR: unfolded protein response; UPP: ubiquitin-proteasome pathway. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

Erratum to ‘Exploring and exploiting the systemic effects of deregulated replication licensing’ [Seminars in Cancer Biology 37–38C, (2016) 3–15](S1044579X15300031)(10.1016/j.semcancer.2015.12.002)

In Fig. 4a the heat map legend is as follows: [figure presented] © 201

Exploring and exploiting the systemic effects of deregulated replication licensing

Maintenance and accurate propagation of the genetic material are key features for physiological development and wellbeing. The replication licensing machinery is crucial for replication precision as it ensures that replication takes place once per cell cycle. Thus, the expression status of the components comprising the replication licensing apparatus is tightly regulated to avoid re-replication; a form of replication stress that leads to genomic instability, a hallmark of cancer. In the present review we discuss the mechanistic basis of replication licensing deregulation, which leads to systemic effects, exemplified by its role in carcinogenesis and a variety of genetic syndromes. In addition, new insights demonstrate that above a particular threshold, the replication licensing factor Cdc6 acts as global transcriptional regulator, outlining new lines of exploration. The role of the putative replication licensing factor ChlR1/DDX11, mutated in the Warsaw Breakage Syndrome, in cancer is also considered. Finally, future perspectives focused on the potential therapeutic advantage by targeting replication licensing factors, and particularly Cdc6, are discussed. © 2015 Elsevier Ltd