B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of B-cell receptor (BCR) signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 complex that links BCR signaling to the NF-κB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls an MYC-driven gene expression network predominantly through increasing MYC protein stability. Thus, our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1-induced MYC regulation is not restricted to MCL, but represents a common mechanism. MYC itself is pivotal for MCL survival because its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy of targeting the MALT1-MYC axis in MCL patients

International Validation of a Nomogram to Predict Recurrence after Resection of Grade 1 and 2 Nonfunctioning Pancreatic Neuroendocrine Tumors

Background: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors. Methods: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence. Results: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80). Conclusions: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com

Memory-experience gap in early adolescents' happiness reports

Studies among adult populations show that estimates of how happy one has felt in the past tend to be more positive than average happiness as assessed using time sampling techniques. This ‘memory-experience gap’ is attributed to cognitive biases, among which fading affect bias. In this paper we report a study among 352 pupils of a secondary school in the Netherlands. These youngsters reported subsequently: 1) how happy they had felt yesterday, 2) how happy they had felt during the last month, 3) what they had done the previous day and 4) how the

Plutonium in Soils from Northeast China and Its Potential Application for Evaluation of Soil Erosion

Surface and soil core samples from northeast China were analyzed for Pu isotopes. The measured Pu-240/Pu-239 atomic ratios and Pu239 + 240/Cs-137 activity ratios revealed that the global fallout is the dominant source of Pu and Cs-137 at these sites. Migration behavior of Pu varying with land type and human activities resulted in different distribution of Pu in surface soils. A sub-surface maximum followed by exponential decline of Pu239 + 240 concentrations was observed in an undisturbed soil core, with a total Pu239 + 240 inventory of 86.9 Bq/m(2) and more than 85% accumulated in 0 similar to 20 cm layers. While only half inventory of Pu was obtained in another soil core and no sub-surface maximum value occurred. Erosion of topsoil in the site should be the most possible reason for the significantly lower Pu inventory, which is also supported by the reported Cs-137 profiles. These results demonstrated that Pu could be applied as an ideal substitute of Cs-137 for soil erosion study in the future.</p

The Bitter Truth About Sugar and Willpower: The Limited Evidential Value of the Glucose Model of Ego Depletion

This work was supported by European Research Council Grant 283849 (to N. Gold) under the European Union’s Seventh Framework Programme (FP/2007–2013)

Endogeneity in the Relation between Poverty, Wealth and Life Satisfaction

This publication concentrates on the complex interplay between poverty, wealth and life satisfaction. Main areas of life are quantified in a multidimensional approach of poverty and wealth: Individual income, current health, occupational autonomy or employment status and also the mentioned life satisfaction. Data used in this publication were made available by the German Socio Economic Panel Study (SOEP) at the German Institute for Economic Research (DIW Berlin), Berlin. A period from 1998-2009 is examined. This study has two main goals: (1) To contribute to the interconnection between poverty, wealth and life satisfaction. (2) Besides, the endogeneity research regarding life satisfaction should be expanded. Reduced form vector-autoregressions (with first differences) were used to answer the questions. Therefore, granger-causality can be supposed. Major findings: An initial rise in life satisfaction can improve income and health, but not job autonomy. However, even the probability of returning from unemployment to employment can increase. Gender-specific differences are discussed.Der Fokus dieser Arbeit liegt auf der komplexen Wechselwirkung zwischen Armut, Reichtum und Lebenszufriedenheit. Die Konzentration gilt zentralen Bereichen des Lebens: Individuelles Einkommen, subjektiver Gesundheitszustand, berufliche Autonomie bzw. Erwerbstätigkeit sowie der angesprochenen Lebenszufriedenheit. Die Daten dieser Publikation beruhen auf Zahlen des Soziooekonomischen Panels (SOEP) am Deutschen Institut für Wirtschaftsforschung (DIW Berlin), Berlin. Es wird ein Zeitraum von 1998-2009 betrachtet. Dadurch wird überwiegend ein Beitrag zur Endogenitätsfrage geleistet und das verzweigte Zusammenspiel dieser Größen abgebildet. Methodisch wird dazu auf Reduced Form Vektorautoregressionen (mit First Differences) zurückgegriffen. Granger-Kausalität kann angenommen werden. Zentrale Ergebnisse: Ein anfänglicher Anstieg der Zufriedenheit erhöht das individuelle Einkommen sowie den Gesundheitszustand, aber nicht die berufliche Autonomie. Hingegen kann sich die Wahrscheinlichkeit erhöhen, dass man von einer Arbeitslosigkeit zurück in die Vollerwerbstätigkeit gelangt. Diskrepanzen zwischen den Geschlechtern werden diskutiert

Dissatisfied with Life or with Being Interviewed? Happiness and Motivation to Participate in a Survey

Information on the number of interviewer contacts allows insights into how people's responses to questions on happiness are connected to the difficulty of reaching potential participants. Using the paradata of the German Socio-Economic Panel Study (SOEP), this paper continues such research by revealing a strong link between respondent motivation and reported happiness. Analyses of responses by future non-respondents substantiate this finding and shed light on a key question for empirical research on subjective well-being, which is whether the unhappy tend to avoid survey participation or whether the unwilling might respond more negatively when being asked about their satisfaction with life

Sensitivity to musical emotion is influenced by tonal structure in congenital amusia

Emotional communication in music depends on multiple attributes including psychoacoustic features and tonal system information, the latter of which is unique to music. The present study investigated whether congenital amusia, a lifelong disorder of musical processing, impacts sensitivity to musical emotion elicited by timbre and tonal system information. Twenty-six amusics and 26 matched controls made tension judgments on Western (familiar) and Indian (unfamiliar) melodies played on piano and sitar. Like controls, amusics used timbre cues to judge musical tension in Western and Indian melodies. While controls assigned significantly lower tension ratings to Western melodies compared to Indian melodies, thus showing a tonal familiarity effect on tension ratings, amusics provided comparable tension ratings for Western and Indian melodies on both timbres. Furthermore, amusics rated Western melodies as more tense compared to controls, as they relied less on tonality cues than controls in rating tension for Western melodies. The implications of these findings in terms of emotional responses to music are discussed

A Note on the High Stability of Happiness: The Minimal Effects of a Nuclear Catastrophe on Life Satisfaction

Using life satisfaction as a direct measure of individual utility has become popular in the empirical economic literature. In this context, it is crucial to know what circumstances or changes the measure is sensitive to. Is life satisfaction a volatile concept that is affected by minor changes in life circumstances? Or is it a reliable measure of personal happiness? This paper will analyze the impact of a catastrophe, namely the nuclear catastrophe of Chernobyl, on life satisfaction. I use longitudinal data from the German Socio-Economic Panel Study and especially information collected on a monthly basis which allows the researcher to study calendar effects. The following clear-cut results are found. While concern about the environment rose immediately after the nuclear incident, life satisfaction changed little. This suggests that although people were aware of the severity of the catastrophe, they did not feel that their individual well-being had been affected. This finding is highly relevant to the life satisfaction literature as it shows that the life satisfaction measure is very stable and robust against societal and global events. It is shown to predominantly reflect personal life circumstances like health, employment, income, and the family situation and this relationship is apparently not disturbed by global events. Thus, my results reinforce previous findings on the relationship between life satisfaction and individual life characteristics as the stability of their outcome measure is approved

Parents Transmit Happiness Along with Associated Values and Behaviors to their Children - A Lifelong Happiness Dividend?

There are strong two-way links between parent and child happiness (life satisfaction), even for 'children' who have grown up, moved to their own home and partnered themselves. German panel evidence shows that transmission of (un)happiness from parents to children is partly due to transmission of values and behaviors known to be associated with happiness (Headey, Wagner and Muffels, 2010, 2012). These values and behaviors include giving priority to pro-social and family values, rather than material values, maintaining a preferred balance between work and leisure, active social and community participation, and regular exercise. Both parents have about equal influence on the values and behaviors which children adopt. However, the life satisfaction of adult 'children' continues to be directly influenced by the life satisfaction of their mothers, with the influence of fathers being only indirect, via transmission of values and behaviors. There appears to be a lifelong happiness dividend (or unhappiness dividend) due to parenting. Structural equation models with two-way causation indicate that the life satisfaction of offspring can significantly affect the satisfaction of their parents, as well as vice-versa, long after the 'children' have left home. Data come from 25 waves of the German Socio-Economic Panel Survey (SOEP, 1984-2008). SOEP is the only panel survey worldwide in which data on life satisfaction have been obtained from parents and an adequate sub-sample of children no longer living in the parental home