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Purpose The purpose of this paper is to offer an integrated framework for understanding agility. Agility has become an increasingly important capability in today’s changing business world. In this paper, the authors suggest “3, 4’s” to better define agility. Agility can be defined through four dimensions (create the future, anticipate opportunity, adapt quickly and learn always); agility occurs with four stakeholders (strategy, organization, leader and individual); and agility is sustained through four Human Resource (HR) tools (people, performance, information and work). Design/methodology/approach Using this integrated framework, executives can better define, assess and invest in creating agility as a capability. Findings The authors studied leading Chinese and US high-tech organizations to discover how they respond to changing market conditions. Originality/value The research for this agility framework is described in their book, Reinventing the Organization: How Companies Can Deliver Radically Greater Value in Fast-Changing Markets.

We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides—2′-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2′-desoxy molecule (GS-560660)—with significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and H. influenzae. We tested their effects on efferocytosis, phagocytosis of NTHi, cell viability, receptors involved in recognition of apoptotic cells and/or NTHi (flow cytometry), secreted and cleaved intracellular IL-1β (cytometric bead array, immunofluorescence/confocal microscopy), and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) using primary alveolar macrophages and THP-1 macrophages ± 10% cigarette smoke extract. Dose-response experiments showed optimal prophagocytic effects of GS-459755 and GS-560660 at concentrations of 0.5–1 µg/ml compared with our findings with azithromycin. Both macrolides significantly improved phagocytosis of apoptotic cells and NTHi (e.g., increases in efferocytosis and phagocytosis of NTHi: GS-459755, 23 and 22.5%, P = 0.043; GS-560660, 23.5 and 22%, P = 0.043, respectively). Macrophage viability remained >85% following 24 h exposure to either macrolide at concentrations up to 20 µg/ml. Secreted and intracellular-cleaved IL-1β was decreased with both macrolides with no significant changes in recognition molecules c-mer proto-oncogene tyrosine kinase; scavenger receptor class A, member 1; Toll-like receptor 2/4; or CD36. Particulate cytoplasmic immunofluorescence of NLRP3 inflammasome was also reduced significantly. We conclude that GS-459755 and GS-560660 may be useful for reducing airway inflammation in chronic lung diseases without inducing bacterial resistance.

Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) is an appealing target for several hematological malignancies and inflammatory diseases. Herein, we describe the discovery and optimization of a series of propeller shaped PI3Kδ inhibitors comprising a novel triaminopyrimidine hinge binder. Combinations of electronic and structural strategies were employed to mitigate aldehyde oxidase mediated metabolism. This medicinal chemistry effort culminated in the identification of 52, a potent and highly selective inhibitor of PI3Kδ that demonstrates efficacy in a rat model of arthritis.

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2′-desoxy-9-( S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC50 ∼3.9 μM) and comparable to the antibacterial macrolide azithromycin (IC50 ∼2.4 μM). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance.

Changing competitive dynamics are influencing the leadership capability requirements of global corporations. More than 1,200 managers from ten major global corporations in eight countries responded to an international survey on the core capabilities required for competitiveness. While the results highlighted six leadership capabilities that are globally valued, a comparative analysis of the data shows that culture affects the relative importance given to a leadership capability requirement. The article also investigates the most effective methods for developing each of the core leadership capabilities. Implications for HR professionals are suggested as they devise strategies for leadership development. © 1995 by John Wiley & Sons, Inc.

With data from 12,689 associates of human resource (HR) professionals in 1500 businesses in 109 firms, this research represents an extensive assessment of HR competencies. It extends current HR theory and practice in two ways. First, it proposes specific competencies HR professionals may demonstrate to add value to a business. Second, it offers an empirical assessment of how these competencies affect the performance of HR professionals as perceived by their Associates. The results indicate that when HR professionals demonstrate competencies in business knowledge, delivery of HR, and management of change, then HR professionals are perceived by their associates as more effective. © 1995 by John Wiley & Sons, Inc.

In this introductory note, we offer an overview of how human resource management in Asian countries and corporations is evolving in the face of rapid business growth and integration into the global economy and we describe how the articles in this Special Issue contribute to new knowledge and insights regarding key issues, challenges, and evolution in the field of HRM in Asia. Driven by the combined forces of rapid gross domestic product growth in many Asian economies and their further integration into the global business arena, firms in Asia are in constant flux, no matter whether they are developed economies like Japan, Korea, andTaiwan; developing economies like Malaysia andThailand; or transitional economies like China and Vietnam. How will HRM systems in these countries evolve and transform under the combined forces of growth and globalization? We argue that HRM systems in these Asian firms most likely will evolve toward “bounded convergence.” The demands and expectations of the HR function to take on strategic roles (versus administrative roles) and address critical HR issues like attracting and retaining key talent, building talent pipelines, and creating high-performing cultures are greater than ever. We conclude with a high-level summary of the key contribution of the eight articles covered in this Special Issue.

While all global leaders aspire to build a winning global company – one that is competitive, profitable, and sustainable – the business strategies and organizational models they pursue vary substantially, depending on the external and internal business environments they face. In this article, we outline the journey of Acer's growth and transformation from the founding of the company in 1976 to the end of 2004. Throughout this period, the Acer Group had grown tremendously and been transformed radically to adapt to the changing competitive dynamics of the global PC industry. We describe the two major transformations in strategy and organization implemented by Acer's global leadership teams to maintain and enhance the global competitiveness of Acer Inc. in a turbulent industry where many players had disappeared in the last two decades. Based on our reflections on Acer's journey, we also highlight five key roles that global leaders play in building the sustained competitiveness of their companies. We believe that leaders must (1) develop innovative business models to leverage global resources for profitable global growth; (2) be sensitive to external environmental trends and internal bottlenecks and act on them proactively; (3) communicate persuasively with key stakeholders to gain commitment to the change; (4) reverse the negative vicious cycle of low performance into a positive virtuous cycle of growth; (5) be positive and optimistic in the midst of adversity so that opportunities for turnaround and eventual growth can be found. In industries that are fast-changing and highly competitive, we believe that it is more imperative than ever for global leaders to demonstrate such leadership roles and capabilities in order to navigate their companies through the turbulent times.

Many Human Resource (HR) professionals feel and believe that they have made progress during the 1980s. Unfortunately, without data to benchmark progress, assessments must depend on perception rather than evidence. To move beyond belief towards a national HR database, this article reports research on over 10,000 individuals in 1200 businesses in 91 firms. It establishes a benchmark for HR practices and HR professionals. It also highlights areas where HR professionals may focus attention to become more successful as business partners.