Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
320
result(s) for
"Lambert, Caroline"
Sort by:
You don't lose 'til you quit trying : lessons on adversity and victory from a Vietnam veteran and Medal of Honor recipient
\"The inspiring true life story of Vietnam veteran, Medal of Honor recipient and veteran's advocate Sammy Lee Davis. On November 18th, 1967, Private First Class Davis's artillery unit was hit by a massive enemy offensive. At twenty-one years old, he resolved to face the onslaught and prepared to die. Soon he would have a perforated kidney, crushed ribs, a broken vertebra, his flesh ripped by beehive darts, a bullet in his thigh, and burns all over his body. Ignoring his injuries, he manned a two-ton Howitzer by himself, crossed a canal under heavy fire to rescue three wounded American soldiers, and kept fighting until the enemy retreated. His heroism that day earned him a Congressional Medal of Honor--the ceremony footage of which ended up being used in the movie Forrest Gump. You Don't Lose 'Til You Quit Trying chronicles how his childhood in the American Heartland prepared him for the worst night of his life--and how that night set off a lifetime battling against debilitating injuries, the effects of Agent Orange and an America that was turning on its veterans. But he also battled for his fellow veterans, speaking on their behalf for forty years to help heal the wounds and memorialize the brotherhood that war could forge. Here, readers will learn of Sammy Davis's extraordinary life--the courage, the pain, and the triumph\"-- Provided by publisher.
Book
Exploring differences in budget characteristics, roles and satisfaction: A configurational approach
This study proposes a taxonomy of budget configurations. Combining a qualitative analysis and a cluster analysis, we identify five patterns of budget design and budget use: the yardstick budget, the coercive budget, the interactive budget, the loose budget and the indicative budget. Our taxonomy of budget configurations allows us to describe complex arrangements that arise in practice. We observe that the budget is less criticized when the level of participation, the level of involvement of managers and the importance assigned to action plans during budget negotiations are high. This study refines the representation of budgetary practices, opening the way to a better understanding of the practice of budgeting.
Paper
The unlocked leader : dare to free your own voice, lead with empathy, and shine your light in the world
\"For decades, the traditional view was that to be successful, business leaders must be superheros?infallible, unflappable, in control, and fearless?or at least pretend to be. As a global executive coach, I work with many superhero-leaders. These smart and successful executives are masters at leading with their head. Yet they don't know how to lead with their heart and their soul, too. In today's unpredictable and fast-changing business environment, no single person has all the answers. The best leaders are strong *and* vulnerable?they show their human weaknesses as a way to connect with people, create a safe and supportive environment, and mobilize them around an inspiring vision. If this sounds like la-la land, consider this. First, the world has changed. Second, employees have changed, too. Over half are struggling, feeling overworked, disconnected, unheard and suffering from digital burnout. To give the best of themselves, they need leaders who are human, too, unafraid of showing empathy and vulnerability: not distant semi-gods with whom there can be no genuine connection. The leader's journey involves three steps: first identifying the mind trap that stands in the way, then operating a mind-shift to defuse it, and finally engineering a mind-build to anchor a new perspective\"-- Provided by publisher.
Book
Mothering or auditing? The case of two Big Four in France
Purpose - Women in public accounting firms are still proportionally much fewer in number in the highest levels of the hierarchy than men, whereas recruitment at junior level tends to be increasingly gender-balanced. This paper aims to analyse the relationships between the glass ceiling and motherhood. The mechanisms explaining the difficulties encountered by auditor mothers in their hierarchical progression within the Big Four in France are identified. Design/methodology/approach - From 24 interviews with male and female auditors of various hierarchical levels, one seeks to reveal the specificity of the difficulties encountered by auditor mothers. Findings - It is argued that, throughout their careers, they are confronted with a dilemma that often leads to their being excluded and excluding themselves from the group of \"those who may become partners\". It is shown that public accounting firms place both implicit and explicit obstacles in their way, tied to a desire to neutralise the effects, deemed costly, of motherhood. Moreover, the expectations of the organisation and society as a whole conflict on many points and confront female auditors with a dilemma: how to be a good mother and have a bright career? It appears that women who want to better manage this dilemma shape working practices imposed on the whole team and implement tactics to adapt their work-life balance (specialisation and lateral move to staff departments). This leads to individual trajectories that break out of the organisational model and account for the scarcity of women in the upper management levels in audit firms. Originality/value - The paper gives voice to male auditors and shows that managing the professional life/private life dilemma is difficult for fathers as well as mothers, in the long term. Moreover, rather than thinking in terms of horizontal and vertical segregations, this paper invites one to question the concept of the glass ceiling and consider the construction of the scarcity of women in the accounting profession.
Journal Article
FOXM1 promotes pulmonary artery smooth muscle cell expansion in pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) is a progressive vascular remodeling disease characterized by a persistent elevation of pulmonary artery pressure, leading to right heart failure and premature death. Exaggerated proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) is a key component of vascular remodeling. Despite major advances in the field, current therapies for PAH remain poorly effective in reversing the disease or significantly improving long-term survival. Because the transcription factor FOXM1 is necessary for PASMC proliferation during lung morphogenesis and its overexpression stimulates proliferation and evasion of apoptosis in cancer cells, we thus hypothesized that upregulation of FOXM1 in PAH-PASMCs promotes cell expansion and vascular remodeling. Our results showed that FOXM1 was markedly increased in distal pulmonary arteries and isolated PASMCs from PAH patients compared to controls as well as in two preclinical models. In vitro, we showed that miR-204 expression regulates FOXM1 levels and that inhibition of FOXM1 reduced cell proliferation and resistance to apoptosis through diminished DNA repair mechanisms and decreased expression of the pro-remodeling factor survivin. Accordingly, inhibition of FOXM1 with thiostrepton significantly improved established PAH in two rat models. Thus, we show for the first time that FOXM1 is implicated in PAH development and represents a new promising target.Key messagesFOXM1 is overexpressed in human PAH-PASMCs and PAH animal models.FOXM1 promotes PAH-PASMC proliferation and resistance to apoptosis.Pharmacological inhibition of FOXM1 improves established PAH in the MCT and Su/Hx rat models.FOXM1 may be a novel therapeutic target in PAH.
Journal Article
HDAC6: A Novel Histone Deacetylase Implicated in Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease with limited therapeutic options. Although exposed to stressful conditions, pulmonary artery (PA) smooth muscle cells (PASMCs) exhibit a “cancer-like” pro-proliferative and anti-apoptotic phenotype. HDAC6 is a cytoplasmic histone deacetylase regulating multiple pro-survival mechanisms and overexpressed in response to stress in cancer cells. Due to the similarities between cancer and PAH, we hypothesized that HDAC6 expression is increased in PAH-PASMCs to face stress allowing them to survive and proliferate, thus contributing to vascular remodeling in PAH. We found that HDAC6 is significantly up-regulated in lungs, distal PAs, and isolated PASMCs from PAH patients and animal models. Inhibition of HDAC6 reduced PAH-PASMC proliferation and resistance to apoptosis
in vitro
sparing control cells. Mechanistically, we demonstrated that HDAC6 maintains Ku70 in a hypoacetylated state, blocking the translocation of Bax to mitochondria and preventing apoptosis.
In vivo
, pharmacological inhibition of HDAC6 improved established PAH in two experimental models and can be safely given in combination with currently approved PAH therapies. Moreover,
Hdac6
deficient mice were partially protected against chronic hypoxia-induced pulmonary hypertension. Our study shows for the first time that HDAC6 is implicated in PAH development and represents a new promising target to improve PAH.
Journal Article
Numerical Simulation of Self-Sustained Roll Oscillations of an 80-Degree Delta Wing Caused by Leading-Edge Vortices
Numerical simulations of an 80-degree delta wing in free-to-roll motion are performed by applying the dynamic fluid–body interaction (DFBI) model and the overlap/chimera method using the URANS equations. The capabilities of modern computational fluid dynamics methods for predicting wing-rock phenomena over a wide range of angles of attack at low Mach numbers and strong wing–vortex interaction, including the vortex breakdown phenomenon, were investigated by comparing simulation results with wind tunnel test data. At low angles of attack, delays in the strength and position of the leading-edge vortices above the wing have a destabilizing effect on it, leading to the emergence of self-sustained limit-cycle oscillations. At high angles of attack, where vortex breakdown occurs, the available wind tunnel data show that there are two modes of wing self-oscillations in free-to-roll motion, namely, regular large-amplitude oscillations and irregular small-amplitude oscillations, where the excitation of the latter mode depends on the angle of attack and the initial roll angle of the wing motion. The performed numerical simulation also shows the existence of these two self-oscillatory modes in roll, qualitatively and quantitatively matching the experimental data.
Journal Article
Krüppel-like Factor 5 contributes to pulmonary artery smooth muscle proliferation and resistance to apoptosis in human pulmonary arterial hypertension
Background
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized by enhanced proliferation of pulmonary artery smooth muscle cell (PASMC) and suppressed apoptosis. This phenotype has been associated with the upregulation of the oncoprotein survivin promoting mitochondrial membrane potential hyperpolarization (decreasing apoptosis) and the upregulation of growth factor and cytokines like PDGF, IL-6 and vasoactive agent like endothelin-1 (ET-1) promoting PASMC proliferation. Krüppel-like factor 5 (KLF5), is a zinc-finger-type transcription factor implicated in the regulation of cell differentiation, proliferation, migration and apoptosis. Recent studies have demonstrated the implication of KLF5 in tissue remodeling in cardiovascular diseases, such as atherosclerosis, restenosis, and cardiac hypertrophy. Nonetheless, the implication of KLF5 in pulmonary arterial hypertension (PAH) remains unknown. We hypothesized that KLF5 up-regulation in PAH triggers PASMC proliferation and resistance to apoptosis.
Methods and results
We showed that KFL5 is upregulated in both human lung biopsies and cultured human PASMC isolated from distal pulmonary arteries from PAH patients compared to controls. Using stimulation experiments, we demonstrated that PDGF, ET-1 and IL-6 trigger KLF-5 activation in control PASMC to a level similar to the one seen in PAH-PASMC. Inhibition of the STAT3 pathway abrogates KLF5 activation in PAH-PASMC. Once activated, KLF5 promotes cyclin B1 upregulation and promotes PASMC proliferation and triggers survivin expression hyperpolarizing mitochondria membrane potential decreasing PASMC ability to undergo apoptosis.
Conclusion
We demonstrated for the first time that KLF5 is activated in human PAH and implicated in the pro-proliferative and anti-apoptotic phenotype that characterize PAH-PASMC. We believe that our findings will open new avenues of investigation on the role of KLF5 in PAH and might lead to the identification of new therapeutic targets.
Journal Article
The Conserved YPX3L Motif in the BK Polyomavirus VP1 Protein Is Important for Viral Particle Assembly but Not for Its Secretion into Extracellular Vesicles
The BK polyomavirus (BKPyV) is a small DNA non-enveloped virus whose infection is asymptomatic in most of the world’s adult population. However, in cases of immunosuppression, the reactivation of the virus can cause various complications, and in particular, nephropathies in kidney transplant recipients or hemorrhagic cystitis in bone marrow transplant recipients. Recently, it was demonstrated that BKPyV virions can use extracellular vesicles to collectively traffic in and out of cells, thus exiting producing cells without cell lysis and entering target cells by diversified entry routes. By a comparison to other naked viruses, we investigated the possibility that BKPyV virions recruit the Endosomal-Sorting Complexes Required for Transport (ESCRT) machinery through late domains in order to hijack extracellular vesicles. We identified a single potential late domain in the BKPyV structural proteins, a YPX3L motif in the VP1 protein, and used pseudovirions to study the effect of point mutations found in a BKPyV clinical isolate or known to ablate the interaction of such a domain with the ESCRT machinery. Our results suggest that this domain is not involved in BKPyV association with extracellular vesicles but is crucial for capsomere interaction and thus viral particle assembly.
Journal Article