Evaluation of a Pseudo-R2 Measure for Panel Probit Models

A simulation study designed to evaluate the pseudo-R2 T proposed by Spiess and Keller (1999) suggests that this measure represents the goodness- of-fit not only of the systematic part, but also of the assumed correlation structure in binary panel probit models.Goodness-of-fit; Pseudo-R2; Panel probit model; Simulation study

Derivation of Design Weights: The Case of the German Socio-Economic Panel (GSOEP)

Design-based estimators of totals, means or proportions in finite populations generally are functions of weighted sums. If each element selected into the sample is also observed, then for the calculation of the pi-estimator these weights are just the inverse inclusion probabilities of the elements. However, if e.g. nonresponse or attrition over time occurs, calculation of these weights also includes modeling of nonresponse and/or attrition mechanisms. Since models of these mechanisms are disputable, 'pure' design weights can be the basis for calculating alternative weights by a different modeling e.g. of nonresponse and/or attrition mechanisms. In the case of complex sampling schemes, however, it is often not possible to derive the exact inclusion probabilities. In that case, weights may be derived based on approximations and/or simplifying assumptions. In this paper, after describing the selection schemes of the subsamples A, B, C, D and E of the German Socio-Economic Panel (GSOEP), approximate design weights are derived which enable users of the GSOEP to calculate their own weights if desired.Design-based inference; approximate design weights; complex surveys; GSOEP

Integration of transmembrane domains is regulated by their downstream sequences

The Sec61 translocon catalyzes translocation of proteins into the endoplasmic reticulum and the lateral integration of transmembrane segments into the lipid bilayer. Integration is mediated by the hydrophobicity of a polypeptide segment consistent with thermodynamic equilibration between the translocon and the lipid membrane. Integration efficiency of a generic series of increasingly hydrophobic sequences (H-segments) was found to diverge significantly in different reporter constructs as a function of the ∼100 residues carboxyterminal of the H-segments. The hydrophobicity threshold of integration was considerably lowered by insertion of generic ∼20-residue peptides either made of flexible glycine-serine repeats, containing multiple negative charges, or consisting of an oligo-proline stretch. A highly flexible, 100-residue glycine-serine stretch maximally enhanced this effect. The apparent free energy of integration was found to be changed by more than 3 kcal/mol with the downstream sequences tested. The C-terminal sequences could also be shown to affect integration of natural mildly hydrophobic sequences. The results suggest that the conformation of the nascent polypeptide in the protected cavity between ribosome and translocon significantly influences the release of the H-segment into the bilayer

Genetic forms of neurohypophyseal diabetes insipidus

In the majority of cases, hereditary neurohypophyseal diabetes insipidus (DI) is a monogenic disorder caused by mutations in the AVP gene. Dominant transmission is by far the most common form. In these patients, symptoms develop gradually at various ages during childhood, progressing with complete penetrance to polyuria and polydipsia that is usually severe. In autosomal dominant neurohypophyseal DI (ADNDI), the mutant prohormone is folding deficient and consequently retained in the ER, where it forms amyloid-like fibrillar aggregates. Degradation by proteasomes occurs, but their clearance capacity appears to be insufficient. Postmortem studies in affected individuals suggest a neurodegenerative process confined to vasopressinergic neurons. Other forms of genetic neurohypophyseal DI include the very rare autosomal recessive type, also caused by mutations in the AVP gene, and complex multiorgan disorders, such as Wolfram syndrome. In all individuals where a congenital form of DI is suspected, including nephrogenic types, genetic analysis should be performed

On the treatment of non-original sample members in the German Household Panel Study (SOEP)

'Haushalts-Panel-Datensätze stellen üblicherweise Daten für Eltern, Kinder und Geschwister zur Verfügung, nicht aber Daten aller Ex-Partner nach einer Scheidung oder nach der Trennung von Lebenspartnern. Diese Information stellt jedoch eine interessante Datenquelle für intergenerationale Untersuchungen beziehungsweise allgemeiner, für Untersuchungen zur Dynamik des Lebenslaufes dar. Unseres Wissens nach sind Daten über Personen, die in Welle zwei oder später in einen Panelhaushalt einziehen und diesen danach wieder verlassen, nur im Sozio-oekonomischen Panel (SOEP) verfügbar. Im SOEP werden alle Personen weiterverfolgt, die einmal in einem Panelhaushalt gelebt haben. Im vorliegenden Papier diskutieren wir die Idee, die den Weiterverfolgungsregeln bezüglich der Neuzugänge nicht-originale Stichprobenmitglieder des SOEP zugrunde liegt. Präsentiert werden weiterhin Häufigkeiten und damit die Relevanz dieser Stichprobenneuzugänge im SOEP im Allgemeinen und für einige Forschungsfragen im Speziellen.' (Autorenreferat)'Household panel studies usually provide data on parents, children, and siblings, but not, e.g., on all ex-partners after a divorce or split in a cohabiting unit. This kind of information, however, can be an interesting source for intergenerational research or, more generally, for research on the dynamics of life course. To the best of our knowledge, among the diverse household panel studies, only the German Socio-Economic Panel (SOEP) contains data on individuals entering a sample household in or after wave two also after leaving that household again. This allows all household members to be traced once having lived in the sample household. In this paper, we discuss the rationale for tracing non-original sample members (Non-OSMs) in household panel studies. We also present results on the incidence and thus the relevance of Non- OSMs in the SOEP in general, and for specific Research questions in particular.' (author's abstract)

Analyse von Längsschnittdaten mit fehlenden Werten: Grundlagen, Verfahren und Anwendungen.

The first part gives an overview over foundations of empirical social research and an introduction into the estimation of linear fixed and random effects panel models. In addition, the semi parametric estimation of binary panel models based on generalized estimating equations (GEE) is addressed. The standard GEE approach, where the covariance structure parameters are treated as nuisance parameters is then generalized to include estimating equations for both, mean and covariance structure parameters. This approach allows the estimation of simultaneous equations panel models with mixed continuous and ordered categorical outcomes which is discussed in detail. As a measure of the explanatory power of the model a pseudo-R^2 measure is developed and evaluated. In the second part, fundamental concepts important with respect to the analysis of data sets with missing values are introduced and discussed and various approaches and methods to compensate for missing data are reviewed. The method of multiple imputation and its application is treated in detail. The approaches and techniques proposed and discussed in the first two parts are tested and illustrated with the help of various simulation studies and examples, respectively.The last chapter deals with possibly time changing effects of variables that can be interpreted as social investments on variables that can be interpreted as subjective and objective gratification variables. The resulting two-equation panel model with mixed continuous and ordered categorical outcomes is estimated with the approach described in the first part based on a data set with missing values. To compensate for missing data, a mixed weighting and multiple imputation approach is adopted

Retrograde transport of CDMPR depends on several machineries as analyzed by sulfatable nanobodies

Retrograde protein transport from the cell surface and endosomes to the TGN is essential for membrane homeostasis in general and for the recycling of mannose-6-phosphate receptors (MPRs) for sorting of lysosomal hydrolases in particular. We used a nanobody-based sulfation tool to more directly determine transport kinetics from the plasma membrane to the TGN for the cation-dependent MPR (CDMPR) with and without rapid or gradual inactivation of candidate machinery proteins. Although knockdown of retromer (Vps26), epsinR, or Rab9a reduced CDMPR arrival to the TGN, no effect was observed upon silencing of TIP47. Strikingly, when retrograde transport was analyzed by rapamycin-induced rapid depletion (knocksideways) or long-term depletion by knockdown of the clathrin adaptor AP-1 or of the GGA machinery, distinct phenotypes in sulfation kinetics were observed, suggesting a potential role of GGA adaptors in retrograde and anterograde transport. Our study illustrates the usefulness of derivatized, sulfation-competent nanobodies, reveals novel insights into CDMPR trafficking biology, and further outlines that the selection of machinery inactivation is critical for phenotype analysis

Disulphide production by Ero1alpha-PDI relay is rapid and effectively regulated

The molecular networks that control endoplasmic reticulum (ER) redox conditions in mammalian cells are incompletely understood. Here, we show that after reductive challenge the ER steady-state disulphide content is restored on a time scale of seconds. Both the oxidase Ero1alpha and the oxidoreductase protein disulphide isomerase (PDI) strongly contribute to the rapid recovery kinetics, but experiments in ERO1-deficient cells indicate the existence of parallel pathways for disulphide generation. We find PDI to be the main substrate of Ero1alpha, and mixed-disulphide complexes of Ero1 primarily form with PDI, to a lesser extent with the PDI-family members ERp57 and ERp72, but are not detectable with another homologue TMX3. We also show for the first time that the oxidation level of PDIs and glutathione is precisely regulated. Apparently, this is achieved neither through ER import of thiols nor by transport of disulphides to the Golgi apparatus. Instead, our data suggest that a dynamic equilibrium between Ero1- and glutathione disulphide-mediated oxidation of PDIs constitutes an important element of ER redox homeostasis

Rabaptin5 targets autophagy to damaged endosomes and Salmonella vacuoles via FIP200 and ATG16L1

Selective autophagy of damaged organelles is important to maintain cellular homeostasis. The mechanisms how autophagy selects specific targets is often poorly understood. Rabaptin5 was previously known as a major regulator of early endosome identity and maturation. Here, we identify two novel Rabaptin5 interactors: FIP200, a subunit of the ULK1 autophagy initiator complex, and ATG16L1, a central component of the E3-like enzyme in LC3 lipidation. Autophagy of early endosomes damaged by chloroquine or monensin treatment requires Rabaptin5 and particularly a short sequence motif that binds to the WD domain of ATG16L1. Rabaptin5 and its interaction with ATG16L1 further contributes to the autophagic elimination of Salmonella enterica early after infection, when it resides in phagosomes with early endosomal characteristics. Our results demonstrate a novel function of Rabaptin5 in quality control of early endosomes in the selective targeting of autophagy to damaged early endosomes and phagosomes

A Generalized Estimating/Pseudo-Score Equations Approach for the Estimation of Structural Equation Models

The results of two simulation studies suggest a mixed 'generalized estimating/pseudo-score equations' approach to lead to more efficient estimators than a GEE approach proposed by Qu, Williams, Beck and Medendorp (1992) or a three-stage approach as proposed e.g. by Schepers, Arminger and Küsters (1991) in panel probit models with binary responses. Furthermore, the mixed approach led to very efficient estimators of regression and correlation structure parameter estimators in an assumed underlying model relative to the ML estimator for an equicorrelation structure. Using the mixed approach, the regression parameters are estimated using generalized estimating equations and the correlation structure parameters are simultaneously estimated using pseudo-score equations. Both sets of parameters are calculated as if they were orthogonal, thereby preserving the robustness of the regression parameter estimators with respect to misspecification of the correlation matrix. Based on the above simulation results, the mixed approach is extended for the estimation of more general structural equation models with ordered categorical or mixed continuous/ ordered categorical responses.Multivariate probit model; generalized estimating equations; pseudo-score equations; correlated categorical and continuous responses; structural equation models