NPY and cardiac diseases

Hypertension-induced left ventricular hypertrophy (LVH), along with ischemic heart disease, result in LV remodeling as part of a continuum that often leads to congestive heart failure. The neurohormonal model has been used to underpin many treatment strategies, but optimal outcomes have not been achieved. Neuropeptide Y (NPY) has emerged as an additional therapeutic target, ever since it was recognised as an important mediator released from sympathetic nerves in the heart, affecting coronary artery constriction and myocardial contraction. More recent interest has focused on the mitogenic and hypertrophic effects that are observed in endothelial and vascular smooth muscle cells, and cardiac myocytes. Of the six identified NPY receptor subtypes, Y-1, Y-2, and Y-5 appear to mediate the main functional responses in the heart. Plasma levels of NPY become elevated due to the increased sympathetic activation present in stress-related cardiac conditions. Also, NPY and Y receptor polymorphisms have been identified that may predispose individuals to increased risk of hypertension and cardiac complications. This review examines what understanding exists regarding the likely contribution of NPY to cardiac pathology. It appears that NPY may play a part in compensatory or detrimental remodeling of myocardial tissue subsequent to hemodynamic overload or myocardial infarction, and in angiogenic processes to regenerate myocardium after ischemic injury. However, greater mechanistic information is required in order to truly assess the potential for treatment of cardiac diseases using NPY-based drugs.

Improved structure optimization for fuzzy-neural networks

Fuzzy-neural-network-based inference systems are well-known universal approximators which can produce linguistically interpretable results. Unfortunately, their dimensionality can be extremely high due to an excessive number of inputs and rules, which raises the need for overall structure optimization. In the literature, various input selection methods are available, but they are applied separately from rule selection, often without considering the fuzzy structure. This paper proposes an integrated framework to optimize the number of inputs and the number of rules simultaneously. First, a method is developed to select the most significant rules, along with a refinement stage to remove unnecessary correlations. An improved information criterion is then proposed to find an appropriate number of inputs and rules to include in the model, leading to a balanced tradeoff between interpretability and accuracy. Simulation results confirm the efficacy of the proposed method.

A Question of Legitimacy? A Dynamic Perspective on Multinational Firm Control

The control and coordination of a network of geographically and culturally dispersed subsidiaries is one of the most prominent challenges in international management. However, many empirical findings on the effectiveness of various control mechanisms and combinations thereof are still counterintuitive. This study uses longitudinal case studies and cross-sectional interview data to extend control theory by examining why, how, and in what sequence large multinational firms (MNCs) implement controls in their networks of foreign subsidiaries. Our analysis draws from literature on institutional theory, embeddedness, and organizational power to demonstrate that MNC headquarters need to overcome institutional duality when implementing their controls abroad. We find that headquarters do so by using social controls, primarily as a way of legitimizing and institutionalizing their process and output controls that are implemented subsequently.

Evolution of Organisational Structure and Capabilities in Internationalising Banks: The CEE Operations of UniCredit's Vienna Office

Cross-border integration is the central management issue for banks that expand internationally, and this is especially true in Central and Eastern Europe, where the pace of internationalisation through mergers and acquisitions has been rapid. A critical challenge in cross-border integration is aligning a multinational company's formal organizational structure with the distribution of capabilities across its subsidiary units, and this issue is explored by tracking the co-evolution of organizational structure and capabilities during the internationalisation of a large banking network into this region. Our focus is the Vienna head office of Bank Austria Creditanstalt, which was acquired first by HypoVereinsbank (Germany) and then UniCredit (Italy). Despite its formal role being downgraded during these changes, the unit continued to develop its distinctive capabilities. The key insight our article offers is that managing cross-border integration is not simply about recognizing the value of the distinctive capabilities of individual units and designing formal structures that successfully align with them. It is also about understanding the need for dynamic interaction between formal corporate structure and individual units' desires to retain power and influence, which have significant implications for the development of their organizational capabilities.

Stereotypes of Age Differences in Personality Traits: Universal and Accurate?

Age trajectories for personality traits are known to be similar across cultures. To address whether stereotypes of age groups reflect these age-related changes in personality, we asked participants in 26 countries (N = 3,323) to rate typical adolescents, adults, and old persons in their own country. Raters across nations tended to share similar beliefs about different age groups; adolescents were seen as impulsive, rebellious, undisciplined, preferring excitement and novelty, whereas old people were consistently considered lower on impulsivity, activity, antagonism, and Openness. These consensual age group stereotypes correlated strongly with published age differences on the five major dimensions of personality and most of 30 specific traits, using as criteria of accuracy both self-reports and observer ratings, different survey methodologies, and data from up to 50 nations. However, personal stereotypes were considerably less accurate, and consensual stereotypes tended to exaggerate differences across age groups.

Defects in acute responses to TLR4 in Btk-deficient mice result in impaired dendritic cell-induced IFN-γ production by natural killer cells

This study defines a critical role for Btk in regulating TLR4-induced crosstalk between antigen presenting cells (APCs) and natural killer (NK) cells. Reduced levels of IL-12, IL-18 and IFN-? were observed in Btk-deficient mice and ex vivo generated macrophages and dendritic cells (DCs) following acute LPS administration, whilst enhanced IL-10 production was observed. In addition, upregulation of activation markers and antigen presentation molecules on APCs was also impaired in the absence of Btk. APCs, by virtue of their ability to produce IL-12 and IL-18, are strong inducers of NK-derived IFN-?. Co-culture experiments demonstrate that Btk-deficient DCs were unable to drive wild-type or Btk-deficient NK cells to induce IFN-? production, whereas these responses could be restored by exogenous administration of IL-12 and IL-18. Thus Btk is a critical regulator of APC-induced NK cell activation by virtue of its ability to regulate IL-12 and IL-18 production in response to acute LPS administration.

The Birth of Shakespeare's Birthplace

"There is, indeed, little doubt,” the formidable scholar James Orchard Halliwell-Phillipps confidently explained to the Victorian readers of his Outlines of the Life of Shakespeare, “that the Birth-place did not become one of the incentives for pilgrimage until public attention had been specially directed to it at the time of the Jubilee.” That's broadly true. The earliest reference to the three-gabled, half-timbered house (two houses, originally) on Henley Street in Stratford-upon-Avon as the birthplace of William Shakespeare dates only from the late 1750s, when it was so named in Samuel Winter's town map. During the Stratford Jubilee, which David Garrick organized in 1769, the “small old house,” as the actor's first biographer called it, was fully recognized and promoted as the place where Shakespeare was born. Even so, Halliwell-Phillipps's observation conceals more than it reveals, because there is also little doubt that the dwelling that tradition calls Shakespeare's birthplace did not suddenly acquire that status during the first week of September 1769. The process by which the unremarkable piece of real estate that John Shakespeare purchased sometime in the late sixteenth century was transformed into what Barbara Hodgdon has rightly called the “controlling ideological center” of Shakespeare biography was long, slow, and far from inevitable. That process is the subject of this essay.