345 research outputs found

    The impact of CEO characteristics on the international entrepreneurship of small island- based firms

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    This paper examines the impact of CEO characteristics on the International Entrepreneurship (IE) of listed island-based firms (IBFs) during the period 2009-2018. The research considers 164 companies from a sample of eight small islands with securities exchanges including more than one firm headquartered on the island. The selected islands are: Barbados, Cyprus, Fiji, Iceland, Jamaica, Malta, Mauritius, and Trinidad & Tobago. Framed on the upper echelons theory and social network theory, the influence on IE of CEO's tenure, academic background and achievement, family allegiance, and international exposure is studied, taking into account the small island particularities. Through a binary probit model, it is concluded that CEOs' family allegiance, tenure, and academic background (if the CEO majored in Business Administration, Finance, Accounting, or Economics) are negatively related with IE, while CEOs' academic achievement and international exposure are positively associated with IE. Some of these results are atypical in the existing literature; nevertheless, islandness can explain these results. The conclusions attained suggest new theoretical and empirical lines of IE research for IBFs

    Glutamate-mediated blood-brain barrier opening. implications for neuroprotection and drug delivery

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    The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT: In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders

    Identification of sex hormone-binding globulin in the human hypothalamus

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    Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin ( SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin. Copyright (c) 2005 S. Karger AG, Base

    The skeletal phenotype of chondroadherin deficient mice

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    Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their a2b1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3–6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the a1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth

    Limited Liability Companies in Kentucky, Second Edition

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    The Kentucky Limited Liability Company Act, KRS Chapter 275, went into effect July 15, 1994, allowing Kentuckians to conduct business under the LLC form. With over 10,000 LLCs formed in the Commonwealth since the Act\u27s inception, this flexible business entity has become the most popular way to conduct business in Kentucky. The LLC has become so pervasive that business law practitioners, accountants, tax advisors and estate planners must all be well-versed in the myriad of issues and creative applications that accompany this business entity. With flexible tax-treatment and the liability protection of a traditional corporation this entity is utilized not only for business formation and practice but also for business succession and estate planning, the structuring of joint ventures and strategic alliances, as venture capital vehicles, and as tax planning tools. The goal of this monograph is to provide the practitioner with a concise and comprehensive approach to the tools necessary for lawyers to counsel and advise clients on this complex and efficient business entity form. Succinct chapters take the reader through an overview of the LLC entity and the Kentucky LLC Act; choice of entity considerations (both tax and non-tax); the formation, operation and statutory transaction issues which arise for the entity; as well as the new single-member LLC; the professional LLC; the use of the LLC in tax-exempt organizations; wealth transfer planning with LLCs; and securities law, commercial law and benefit issues arising under the LLC entity. Each chapter is set forth in separately numbered paragraphs, present running headers for easy access, and are cross-referenced to other relevant chapters and paragraphs contained in the monograph. Summary and comparative charts, a table of authorities and a statutory appendix are also presented. Finally, a comprehensive index has been created to aid the user in finding relevant subject treatments

    Lentiviral-Mediated Transgene Expression Can Potentiate Intestinal Mesenchymal-Epithelial Signaling

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    Mesenchymal-epithelial signaling is essential for the development of many organs and is often disrupted in disease. In this study, we demonstrate the use of lentiviral-mediated transgene delivery as an effective approach for ectopic transgene expression and an alternative to generation of transgenic animals. One benefit to this approach is that it can be used independently or in conjunction with established transgenic or knockout animals for studying modulation of mesenchymal-epithelial interactions. To display the power of this approach, we explored ectopic expression of a Wnt ligand in the mouse intestinal mesenchyme and demonstrate its functional influence on the adjacent epithelium. Our findings highlight the efficient use of lentiviral-mediated transgene expression for modulating mesenchymal-epithelial interactions in vivo

    Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes

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    This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/R.B.M. was a recipient of a UK Medical Research Council (MRC) studentship, MRC Centenary Award, Barts and The London Charity (472/1711) and Rosetrees Trust (M314), N.K. was a recipient of an MRC studentship (MR/J500409/1), C.J. was a recipient of the Barts and The London Charitable Foundation Scholarship (RAB 05/PJ/07), L.M. was supported by CR-UK, Breast Cancer Now (2008NovPR10) and Rosetrees Trust (M346), A.H. was a recipient of a CR-UK studentship (C236/A11795). P.J.P. was supported by CR-UK. J.I. was supported by grants from the Academy of Finland, ERC Starting grant, Finnish Cancer Organisations and Sigrid Juselius Foundation. S.K. was supported by the MRC (G0501003) and The British Lung Foundation (CAN09-4)

    Characteristics of Sexual Abuse in Childhood and Adolescence Influence Sexual Risk Behavior in Adulthood

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    Childhood and adolescent sexual abuse has been associated with subsequent (adult) sexual risk behavior, but the effects of force and type of sexual abuse on sexual behavior outcomes have been less well-studied. The present study investigated the associations between sexual abuse characteristics and later sexual risk behavior, and explored whether gender of the child/adolescent moderated these relations. Patients attending an STD clinic completed a computerized survey that assessed history of sexual abuse as well as lifetime and current sexual behavior. Participants were considered sexually abused if they reported a sexual experience (1) before age 13 with someone 5 or more years older, (2) between the ages of 13 and 16 with someone 10 or more years older, or (3) before the age of 17 involving force or coercion. Participants who were sexually abused were further categorized based on two abuse characteristics, namely, use of penetration and force. Analyses included 1177 participants (n=534 women; n=643 men). Those who reported sexual abuse involving penetration and/or force reported more adult sexual risk behavior, including the number of lifetime partners and number of previous STD diagnoses, than those who were not sexually abused and those who were abused without force or penetration. There were no significant differences in sexual risk behavior between nonabused participants and those who reported sexual abuse without force and without penetration. Gender of the child/adolescent moderated the association between sexual abuse characteristics and adult sexual risk behavior; for men, sexual abuse with force and penetration was associated with the greatest number of episodes of sex trading, whereas for women, those who were abused with penetration, regardless of whether the abuse involved force, reported the most episodes of sex trading. These findings indicate that more severe sexual abuse is associated with riskier adult sexual behavior
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