Novel Role for the Golgi Membrane Protein TMEM165 in Control of Migration and Invasion for Breast Carcinoma

The TMEM165 gene encodes for a multiple pass membrane protein localized in the Golgi that has been linked to congenital disorders of glycosylation. The TMEM165 protein is a putative ion transporter that regulates H+/Ca++/Mn++ homeostasis and pH in the Golgi. Previously, we identified TMEM165 as a potential biomarker for breast carcinoma in a glycoproteomic study using late stage invasive ductal carcinoma tissues with patient-matched adjacent normal tissues. The TMEM165 protein was not detected in non-malignant matched breast tissues and was detected in invasive ductal breast carcinoma tissues by mass spectrometry. Our hypothesis is that the TMEM165 protein confers a growth advantage to breast cancer. In this preliminary study we have investigated the expression of TMEM165 in earlier stage invasive ductal carcinoma and ductal carcinoma in situ cases. We created a CRISPR/Cas9 knockout of TMEM165 in the human invasive breast cancer cell line MDAMB231. Our results indicate that removal of TMEM165 in these cells results in a significant reduction of cell migration, tumor growth, and tumor vascularization in vivo. Furthermore, we find that TMEM165 expression alters the glycosylation of breast cancer cells and these changes promote the invasion and growth of breast cancer by altering the expression levels of key glycoproteins involved in regulation of the epithelial to mesenchymal transition such as E-cadherin. These studies illustrate new potential functions for this Golgi membrane protein in the control of breast cancer growth and invasion

Black Holes as Effective Geometries

Gravitational entropy arises in string theory via coarse graining over an underlying space of microstates. In this review we would like to address the question of how the classical black hole geometry itself arises as an effective or approximate description of a pure state, in a closed string theory, which semiclassical observers are unable to distinguish from the "naive" geometry. In cases with enough supersymmetry it has been possible to explicitly construct these microstates in spacetime, and understand how coarse-graining of non-singular, horizon-free objects can lead to an effective description as an extremal black hole. We discuss how these results arise for examples in Type II string theory on AdS_5 x S^5 and on AdS_3 x S^3 x T^4 that preserve 16 and 8 supercharges respectively. For such a picture of black holes as effective geometries to extend to cases with finite horizon area the scale of quantum effects in gravity would have to extend well beyond the vicinity of the singularities in the effective theory. By studying examples in M-theory on AdS_3 x S^2 x CY that preserve 4 supersymmetries we show how this can happen.Comment: Review based on lectures of JdB at CERN RTN Winter School and of VB at PIMS Summer School. 68 pages. Added reference

Genetic susceptibility to burnout in a Swedish twin cohort

Most previous studies of burnout have focused on work environmental stressors, while familial factors so far mainly have been overlooked. The aim of the study was to estimate the relative importance of genetic influences on burnout (measured with Pines Burnout Measure) in a sample of monozygotic (MZ) and dizygotic (DZ) Swedish twins. The study sample consisted of 20,286 individuals, born 1959–1986 from the Swedish twin registry who participated in the cross-sectional study of twin adults: genes and environment. Probandwise concordance rates (the risk for one twin to be affected given that his/her twin partner is affected by burnout) and within pair correlations were calculated for MZ and DZ same—and opposite sexed twin pairs. Heritability coefficients i.e. the proportion of the total variance attributable to genetic factors were calculated using standard biometrical model fitting procedures. The results showed that genetic factors explained 33% of the individual differences in burnout symptoms in women and men. Environmental factors explained a substantial part of the variation as well and are thus important to address in rehabilitation and prevention efforts to combat burnout

The use of virtual reality as a potential restorative environment in school during recess

Peer reviewe

Quantizing N=2 Multicenter Solutions

N=2 supergravity in four dimensions, or equivalently N=1 supergravity in five dimensions, has an interesting set of BPS solutions that each correspond to a number of charged centers. This set contains black holes, black rings and their bound states, as well as many smooth solutions. Moduli spaces of such solutions carry a natural symplectic form which we determine, and which allows us to study their quantization. By counting the resulting wavefunctions we come to an independent derivation of some of the wall-crossing formulae. Knowledge of the explicit form of these wavefunctions allows us to find quantum resolutions to some apparent classical paradoxes such as solutions with barely bound centers and those with an infinitely deep throat. We show that quantum effects seem to cap off the throat at a finite depth and we give an estimate for the corresponding mass gap in the dual CFT. This is an interesting example of a system where quantum effects cannot be neglected at macroscopic scales even though the curvature is everywhere small.Comment: 49 pages + appendice

Measuring affective well-being at work using short-form scales : implications for affective structures and participant instructions

Measuring affective well-being in organizational studies has become increasingly widespread, given its association with key work-performance and other markers of organizational functioning. As such, researchers and policy-makers need to be confident that well-being measures are valid, reliable and robust. To reduce the burden on participants in applied settings, short-form measures of affective well-being are proving popular. However, these scales are seldom validated as standalone, comprehensive measures in their own right. In this article, we used a short-form measure of affective well-being with 10 items: the Daniels five-factor measure of affective well-being (D-FAW). In Study 1, across six applied sample groups (N = 2624), we found that the factor structure of the short-form D-FAW is robust when issued as a standalone measure, and that it should be scored differently depending on the participant instruction used. When participant instructions focus on now or today, then affect is best represented by five discrete emotion factors. When participant instructions focus on the past week, then affect is best represented by two or three mood-based factors. In Study 2 (N = 39), we found good construct convergent validity of short-form D-FAW with another widely used scale (PANAS). Implications for the measurement and structure of affect are discussed

Brokering Trust to Enhance Leadership: A Self-Monitoring Approach to Leadership Emergence

What kind of person is likely to emerge as an informal leader in the workplace? Experimental research shows that high self-monitors—who tend to adjust their attitudes and behaviors to the demands of different situations—emerge as informal leaders in temporary groups. By contrast, low self-monitors—who tend to be true to themselves in terms of consistency in attitudes and behaviors across different situations—are less likely to emerge as leaders. But this prior research does not address the criticism that the emergence of high self-monitors as leaders represents ephemeral impression management in the context of laboratory experiments. To address this issue, we collected and analyzed data from a 116-member high-technology firm. Our results show that self-monitoring is related not only to leadership emergence, but also to the provision of advice to co-workers. Further, people who occupied brokerage positions (being trusted by those who did not trust each other) tended to be seen as leaders if they were high rather than low self-monitors. From these results, we build a picture of the high self-monitoring emergent leader as someone who notices problems and ameliorates them through the provision of advice and the brokerage of relationships across social divides. The occupation of a structurally advantageous position may well be more advantageous for some (i.e., high self-monitors) relative to others (i.e., low self-monitors)

The Servant Leadership Survey: Development and Validation of a Multidimensional Measure

Purpose: The purpose of this paper is to describe the development and validation of a multi-dimensional instrument to measure servant leadership. Design/Methodology/Approach Based on an extensive literature review and expert judgment, 99 items were formulated. In three steps, using eight samples totaling 1571 persons from The Netherlands and the UK with a diverse occupational background, a combined exploratory and confirmatory factor analysis approach was used. This was followed by an analysis of the criterion-related validity. Findings: The final result is an eight-dimensional measure of 30 items: the eight dimensions being: standing back, forgiveness, courage, empowerment, accountability, authenticity, humility, and stewardship. The internal consistency of the subscales is good. The results show that the Servant Leadership Survey (SLS) has convergent validity with other leadership measures, and also adds unique elements to the leadership field. Evidence for criterion-related validity came from studies relating the eight dimensions to well-being and performance. Implications: With this survey, a valid and reliable instrument to measure the essential elements of servant leadership has been introduced. Originality/Value The SLS is the first measure where the underlying factor structure was developed and confirmed across several field studies in two countries. It can be used in future studies to test the underlying premises of servant leadership theory. The SLS provides a clear picture of the key servant leadership qualities and shows where improvements can be made on the individual and organizational level; as such, it may also offer a valuable starting point for training and leadership development