The Global Pharmaceutical Industry, 2004

This teaching case looks at the development of the ethical pharmaceutical industry. The various forces affecting the discovery, development, production, distribution and marketing of prescription drugs are discussed in terms of their origins and recent developments. Readers are then invited to consider trends for the future.Ethical pharmaceuticals, industry analysis, five forces

Evidence from the Patent Record on the Development of Cash Dispensing Technology

There are but a handful of systematic studies on the history of automated teller machines (ATMs) yet all fail to address the issue of paternity while perpetrating ‘common wisdom’ beliefs. This article looks at the birth of currency dispensing equipment, the immediate predecessor to the ATM. At the simplest level, at least four separate instance of innovation can reasonably claim to be the origin of the concept. However, the question as to who invented it is less illuminating than an understanding of the process of innovation itself and how these competing families developed into the modern conception of an ATM. Our research supports the view of user-driven innovation as surviving business records and oral histories tell of close involvement of bank staff in establishing requirements and choosing amongst alternative solutions in the implementation of first generation technology. This case thus shows greater understanding in the user’s role in shaping and directing technological development.Cash dispensers (ATMs), History, Financial data processing, Patents, Research and development, User interfaces

Suppression of timing errors in short overdamped Josephson junctions

The influence of fluctuations and periodical driving on temporal characteristics of short overdamped Josephson junction is analyzed. We obtain the standard deviation of the switching time in the presence of a dichotomous driving force for arbitrary noise intensity and in the frequency range of practical interest. For sinusoidal driving the resonant activation effect has been observed. The mean switching time and its standard deviation have a minimum as a function of driving frequency. As a consequence the optimization of the system for fast operation will simultaneously lead to minimization of timing errors.Comment: 4 pages, 4 figures, in press in Physical Review Letter

Giant FAZ10 is required for flagellum attachment zone stabilization and furrow positioning in Trypanosoma brucei

The flagellum and flagellum attachment zone (FAZ) are important cytoskeletal structures in trypanosomatids, being required for motility, cell division and cell morphogenesis. Trypanosomatid cytoskeletons contain abundant high molecular mass proteins (HMMPs), but many of their biological functions are still unclear. Here, we report the characterization of the giant FAZ protein, FAZ10, in Trypanosoma brucei, which, using immunoelectron microscopy, we show localizes to the intermembrane staples in the FAZ intracellular domain. Our data show that FAZ10 is a giant cytoskeletal protein essential for normal growth and morphology in both procyclic and bloodstream parasite life cycle stages, with its depletion leading to defects in cell morphogenesis, flagellum attachment, and kinetoplast and nucleus positioning. We show that the flagellum attachment defects are probably brought about by reduced tethering of the proximal domain of the paraflagellar rod to the FAZ filament. Further, FAZ10 depletion also reduces abundance of FAZ flagellum domain protein, ClpGM6. Moreover, ablation of FAZ10 impaired the timing and placement of the cleavage furrow during cytokinesis, resulting in premature or asymmetrical cell division

Polar relaxation by dynein-mediated removal of cortical myosin II

Nearly 6 decades ago, Lewis Wolpert proposed the relaxation of the polar cell cortex by the radial arrays of astral microtubules as a mechanism for cleavage furrow induction (White and Borisy, 1983; Wolpert, 1960). While this mechanism has remained controversial (Rappaport, 1996), recent work has provided evidence for polar relaxation by astral microtubules (Chen et al., 2008; Dechant and Glotzer, 2003; Foe and Dassow, 2008; Murthy and Wadsworth, 2008; Werner et al., 2007), although its molecular mechanisms remain elusive. Here, using C. elegans embryos, we show that polar relaxation is achieved through dynein-mediated removal of myosin II from the polar cortexes. Mutants that position centrosomes closer to the polar cortex accelerated furrow induction whereas suppression of dynein activity delayed furrowing. We provide evidence that dynein-mediated removal of myosin II from the polar cortexes triggers cortical flow towards the cell equator, which induces the assembly of the actomyosin contractile ring. These studies for the first time provide a molecular basis for the aster-dependent polar relaxation, which works in parallel with equatorial stimulation to promote robust cytokinesis

AN IRRIGATION MODEL FOR MANAGEMENT OF LIMITED WATER SUPPLIES

A two-stage simulation/mathematical programming model is presented for determining the optimal intraseasonal allocation of irrigation water under conditions of limited water supply. The model is applied to a series of water shortage scenarios under both surface and center pivot irrigation. Economically efficient irrigation management is shown to involve the coordination of a number of managerial decisions, including irrigation scheduling, crop substitution, the adoption of improved irrigation labor practices, and idling land. The results indicate that significant opportunities exist for conserving water in the study area under both surface and center pivot irrigation.Crop Production/Industries, Resource /Energy Economics and Policy,

S Equilibrium: A Synthesis of (Behavioral) Game Theory

$S$ equilibrium synthesizes a century of game-theoretic modeling. $S$-beliefs determine choices as in the refinement literature and level-$k$, without anchoring on Nash equilibrium or imposing ad hoc belief formation. $S$-choices allow for mistakes as in QRE, without imposing rational expectations. $S$ equilibrium is explicitly set-valued to avoid the common practice of selecting the best prediction from an implicitly defined set of unknown, and unaccounted for, size. $S$-equilibrium sets vary with a complexity parameter, offering a trade-off between accuracy and precision unlike in $M$ equilibrium. Simple "areametrics" determine the model's parameter and show that choice sets with a relative size of 5 percent capture 58 percent percent of the data. Goodness-of-fit tests applied to data from a broad array of experimental games confirm $S$ equilibrium's ability to predict behavior in and out of sample. In contrast, choice (belief) predictions of level-$k$ and QRE are rejected in most (all) games

Bifurcation Phenomena in Two-Dimensional Piecewise Smooth Discontinuous Maps

In recent years the theory of border collision bifurcations has been developed for piecewise smooth maps that are continuous across the border, and has been successfully applied to explain nonsmooth bifurcation phenomena in physical systems. However, many switching dynamical systems have been found to yield two-dimensional piecewise smooth maps that are discontinuous across the border. The theory for understanding the bifurcation phenomena in such systems is not available yet. In this paper we present the first approach to the problem of analysing and classifying the bifurcation phenomena in two-dimensional discontinuous maps, based on a piecewise linear approximation in the neighborhood of the border. We explain the bifurcations occurring in the static VAR compensator used in electrical power systems, using the theory developed in this paper. This theory may be applied similarly to other systems that yield two-dimensional discontinuous maps