On the compatibility of a flux transport dynamo with a fast tachocline scenario

The compatibility of the fast tachocline scenario with a flux transport dynamo model is explored. We employ a flux transport dynamo model coupled with simple feedback formulae relating the thickness of the tachocline to the amplitude of the magnetic field or to the Maxwell stress. The dynamo model is found to be robust against the nonlinearity introduced by this simplified fast tachocline mechanism. Solar-like butterfly diagrams are found to persist and, even without any parameter fitting, the overall thickness of the tachocline is well within the range admitted by helioseismic constraints. In the most realistic case of a time and latitude dependent tachocline thickness linked to the value of the Maxwell stress, both the thickness and its latitude dependence are in excellent agreement with seismic results. In the nonparametric models, cycle related temporal variations in tachocline thickness are somewhat larger than admitted by helioseismic constraints; we find, however, that introducing a further parameter into our feedback formula readily allows further fine tuning of the thickness variations.Comment: Accepted in Solar Physic

Extracting gamma and Penguin Topologies through CP Violation in B_s^0 -> J/psi K_S

The B_s^0 -> J/psi K_S decay has recently been observed by the CDF collaboration and will be of interest for the LHCb experiment. This channel will offer a new tool to extract the angle gamma of the unitarity triangle and to control doubly Cabibbo-suppressed penguin corrections to the determination of sin(2beta) from the well-known B_d^0 -> J/psi K_S mode with the help of the U-spin symmetry of strong interactions. While any competitive determination of gamma is interesting, the latter aspect is particularly relevant as LHCb will enter a territory of precision which makes the control of doubly Cabibbo-suppressed Standard-Model corrections mandatory. Using the data from CDF and the e^+e^- B factories as a guideline, we explore the sensitivity for gamma and the penguin parameters and point out that the B_s^0-\bar B_s^0 mixing phase phi_s, which is only about -2 deg in the Standard Model but may be enhanced through new physics, is a key parameter for these analyses. We find that the mixing-induced CP violation S(B_s^0 -> J/psi K_S) shows an interesting correlation with sin(phi_s), which serves as a target region for the first measurement of this observable at LHCb.Comment: 20 pages, 8 figure

An official American thoracic society workshop report: Translational research in rare respiratory diseases

Rare respiratory diseases (RRDs) are a heterogeneous group of disorders that collectively represent a significant health care burden. In recent years, strong advocacy and policy initiatives have led to advances in the implementation of research and clinical care for rare diseases. The development of specialized centers and research networks has facilitated support for affected individuals as well as emerging programs in basic, translational, and clinical research. In selected RRDs, subsequent gains in knowledge have informed the development of targeted therapies and effective diagnostic tests, but many gaps persist. There was therefore a desire to identify the elements contributing to an effective translational research program in RRDs. To this end, a workshop was convened in October 2015 with a focus on the implementation of effective transnational research networks and collaborations aimed at developing novel diagnostic and therapeutic tools. Key elements included an emphasis on molecular pathogenesis, the continuing engagement of patient advocacy groups and policy makers, the effective use of preclinical models in the translational research pipeline, and the detailed phenotyping of patient cohorts. During the course of the workshop, current logistical and knowledge gapswere identified, and new solutions or opportunities were highlighted

Regulation of karyopherin alpha1 and nuclear import by mammalian target of rapamycin

Under conditions of reduced mitogen or nutritional substrate levels, the serine/threonine kinase target of rapamycin (TOR) can augment the nuclear content of distinct transcription factors, and promote the induction of stress response genes. In its latent (i.e., unphosphorylated) form, the transcription factor signal transducer and activator of transcription-1 (STAT1) regulates a subset of genes involved in immune modulation and apoptosis. Based on previous work indicating a functional relationship between mTOR and the nuclear content of latent STAT1, we investigate the mechanism by which mTOR controls STAT1 nuclear import. By fluorescence confocal microscopy, inactivation of mTOR with rapamycin promoted the nuclear translocation of unphosphorylated STAT1, but not that of a STAT1 mutant incapable of binding its nuclear import adaptor karyopherin-alpha1 (KPNA1). By immunoprecipitation, KPNA1 was physically associated with mTOR and STAT1 in a complex that translocated to the nucleus in response to rapamycin. Although mTOR was not a kinase for KPNA1, the mTOR-associated phosphatase protein phosphatase 2A catalytic (PP2Ac) interacted directly with KPNA1, and regulated nuclear import of the mTOR/KPNA1 complex. KPNA1, or its interaction with STAT, was required for the nuclear import of latent STAT1, transcriptional induction of the STAT1 gene, and caspase-3 activation under conditions of reduced mTOR activity (i.e., rapamycin, glucose starvation, serum withdrawal). Therefore, at low mitogen or nutrient levels, mTOR and PP2Ac control the constitutive nuclear import of latent STAT1 by KPNA1, which are key modulators of STAT1 expression and apoptosis

Investigating the role of goal orientation in job seekers’ experience of value congruence

There is still limited understanding of how goal orientations influence the association between value congruence (VC) and organisational attraction for job seekers. We address this issue by investigating the impact of individuals’ goal orientations on the VC–attraction relationship. Our investigation using different measurement approaches to congruence across two studies also allowed us to examine the implications of different methods to operationalising VC in job search contexts. Two prominent types of goal orientation in job search—learning‐approach goal orientation (LAGO) and performance‐avoid goal orientation (PAGO)—were hypothesised to moderate the relationship between VC and organisational attraction. In study 1, value congruence based on direct molar perceptions displayed a stronger positive relationship with attraction among low LAGO individuals. Study 2, using separate atomistic judgments of person and organisational values, also demonstrated that LAGO moderates the effects of VC on attraction. However, the form of moderation effects varied across different types of work values (i.e., relationships and security). These findings demonstrate the need to contextualise the study of job seekers’ VC within a goal‐striving context, where different ways of operationalising VC can also shed more light on the psychological processes underlying judgments of congruence.Accepted versio

Downregulation of PERK activity and eIF2α serine 51 phosphorylation by mTOR complex 1 elicits pro-oxidant and pro-death effects in tuberous sclerosis-deficient cells article

Oxidative stress determines cell fate through several mechanisms, among which regulation of mRNA translation by the phosphorylation of the alpha (α) subunit of the translation initiation factor eIF2α at serine 51 (eIF2αP) plays a prominent role. Increased eIF2αP can contribute to tumor progression as well as tumor suppression. While eIF2αP is increased in most cells to promote survival and adaptation to different forms of stress, we demonstrate that eIF2αP is reduced in tuberous sclerosis complex 2 (TSC2)-deficient cells subjected to oxidative insults. Decreased eIF2αP in TSC2-deficient cells depends on reactive oxygen species (ROS) production and is associated with a reduced activity of the endoplasmic reticulum (ER)-resident kinase PERK owing to the hyper-activation of the mammalian target of rapamycin complex 1 (mTORC1). Downregulation of PERK activity and eIF2αP is accompanied by increased ROS production and enhanced susceptibility of TSC2-deficient cells to extrinsic pro-oxidant stress. The decreased levels of eIF2αP delay tumor formation of TSC2-deficient cells in immune deficient mice, an effect that is significantly alleviated in mice subjected to an anti-oxidant diet. Our findings reveal a previously unidentified connection between mTORC1 and eIF2αP in TSC2-deficient cells with potential implications in tumor suppression in response to oxidative insults. © 2018 The Author(s)