Execution: the Critical “What’s Next?” in Strategic Human Resource Management

The Human Resource Planning Society’s 1999 State of the Art/Practice (SOTA/P) study was conducted by a virtual team of researchers who interviewed and surveyed 232 human resource and line executives, consultants, and academics worldwide. Looking three to five years ahead, the study probed four basic topics: (1) major emerging trends in external environments, (2) essential organizational capabilities, (3) critical people issues, and (4) the evolving role of the human resource function. This article briefly reports some of the study’s major findings, along with an implied action agenda – the “gotta do’s for the leading edge. Cutting through the complexity, the general tone is one of urgency emanating from the intersection of several underlying themes: the increasing fierceness of competition, the rapid and unrelenting pace of change, the imperatives of marketplace and thus organizational agility, and the corresponding need to buck prevailing trends by attracting and, especially, retaining and capturing the commitment of world-class talent. While it all adds up to a golden opportunity for human resource functions, there is a clear need to get to get on with it – to get better, faster, and smarter – or run the risk of being left in the proverbial dust. Execute or be executed

Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation

Remodeling of the tricarboxylic acid (TCA) cycle is a metabolic adaptation accompanying inflammatory macrophage activation. During this process, endogenous metabolites can adopt regulatory roles that govern specific aspects of inflammatory response, as recently shown for succinate, which regulates the pro-inflammatory IL-1β-HIF-1α axis. Itaconate is one of the most highly induced metabolites in activated macrophages, yet its functional significance remains unknown. Here, we show that itaconate modulates macrophage metabolism and effector functions by inhibiting succinate dehydrogenase-mediated oxidation of succinate. Through this action, itaconate exerts anti-inflammatory effects when administered in vitro and in vivo during macrophage activation and ischemia-reperfusion injury. Using newly generated Irg1(−/−) mice, which lack the ability to produce itaconate, we show that endogenous itaconate regulates succinate levels and function, mitochondrial respiration, and inflammatory cytokine production during macrophage activation. These studies highlight itaconate as a major physiological regulator of the global metabolic rewiring and effector functions of inflammatory macrophages

Nonlinear behavior of metallic material under constant acceleration loading

There is frequent confusion in literature and in published data of material properties between the strain rate effect and the inertia effect on the behavior of metallic materials. While the measured changes of material behavior due to dynamic loading are frequently referred to as strain rate effects, little emphasis has been given to separating the effects of material inertia. In this work, inertia effects have been investigated during elastic deformations using transient dynamic finite element simulations. The work presents a case study in which a metallic bar is dynamically loaded by constant acceleration in simple tension. The material is assumed to be simple linear elastic. The material behavior is assumed to be time independent, strain rate effect was not considered in the simulations. Controlled axial displacement loading is applied at constant acceleration. When loading the material in the elastic range at high accelerations, the deformation becomes more concentrated towards the point of load application and a larger load is required to achieve a pre-defined displacement at this point, thus resulting in an apparent elasticity modulus higher than that measured at quasi-static conditions. Moreover, the material apparent response becomes non-linear. Keeping in mind that time independent properties have been adopted in the simulation and no strain rate effects have been considered, the resulting changes can be referred to pure inertia effects. In experimental testing, these changes would have been referred to strain-rate effects

Improved mathematical modeling of thermal effects in flexural microcantilever resonators dynamics

In a recent research the thermal dependency of material characteristics in dynamic response of microresonator systems is modeled using Lorentzian function and employing perturbation analysis. Thermal phenomena introduce two main effects: damping due to internal friction, and softening due to Young modulus-temperature relationship. The presented mathematical model provided effective equations to study the electrically actuated microbeam resonators. The mathematical model of thermal phenomena in microbeam vibration was introduced by Jazar (2009). In that analysis, using the Zener model, a positive frequency dependent damping and a negative frequency dependent stiffness terms were introduced to mode the effects of warming at resonance (Jazar 2009). In this investigation, the problem will be analyzed from a practical point of view. We introduce a better mathematical model by improving the presented model. The main difference would be including the strain distribution in the damping and stiffness model

Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis.

Metformin is a biguanide widely prescribed to treat Type II diabetes that has gained interest as an antineoplastic agent. Recent work suggests that metformin directly antagonizes cancer cell growth through its actions on complex I of the mitochondrial electron transport chain (ETC). However, the mechanisms by which metformin arrests cancer cell proliferation remain poorly defined. Here we demonstrate that the metabolic checkpoint kinases AMP-activated protein kinase (AMPK) and LKB1 are not required for the antiproliferative effects of metformin. Rather, metformin inhibits cancer cell proliferation by suppressing mitochondrial-dependent biosynthetic activity. We show that in vitro metformin decreases the flow of glucose- and glutamine-derived metabolic intermediates into the Tricarboxylic Acid (TCA) cycle, leading to reduced citrate production and de novo lipid biosynthesis. Tumor cells lacking functional mitochondria maintain lipid biosynthesis in the presence of metformin via glutamine-dependent reductive carboxylation, and display reduced sensitivity to metformin-induced proliferative arrest. Our data indicate that metformin inhibits cancer cell proliferation by suppressing the production of mitochondrial-dependent metabolic intermediates required for cell growth, and that metabolic adaptations that bypass mitochondrial-dependent biosynthesis may provide a mechanism of tumor cell resistance to biguanide activity

Loss of the tumor suppressor LKB1 promotes metabolic reprogramming of cancer cells via HIF-1α

One of the major metabolic changes associated with cellular transformation is enhanced nutrient utilization, which supports tumor progression by fueling both energy production and providing biosynthetic intermediates for growth. The liver kinase B1 (LKB1) is a serine/threonine kinase and tumor suppressor that couples bioenergetics to cell-growth control through regulation of mammalian target of rapamycin (mTOR) activity; however, the influence of LKB1 on tumor metabolism is not well defined. Here, we show that loss of LKB1 induces a progrowth metabolic program in proliferating cells. Cells lacking LKB1 display increased glucose and glutamine uptake and utilization, which support both cellular ATP levels and increased macromolecular biosynthesis. This LKB1-dependent reprogramming of cell metabolism is dependent on the hypoxia-inducible factor-1α (HIF-1α), which accumulates under normoxia in LKB1-deficient cells and is antagonized by inhibition of mTOR complex I signaling. Silencing HIF-1α reverses the metabolic advantages conferred by reduced LKB1 signaling and impairs the growth and survival of LKB1-deficient tumor cells under low-nutrient conditions. Together, our data implicate the tumor suppressor LKB1 as a central regulator of tumor metabolism and growth control through the regulation of HIF-1α–dependent metabolic reprogramming