Agent-based modeling: a systematic assessment of use cases and requirements for enhancing pharmaceutical research and development productivity.

A crisis continues to brew within the pharmaceutical research and development (R&D) enterprise: productivity continues declining as costs rise, despite ongoing, often dramatic scientific and technical advances. To reverse this trend, we offer various suggestions for both the expansion and broader adoption of modeling and simulation (M&S) methods. We suggest strategies and scenarios intended to enable new M&S use cases that directly engage R&D knowledge generation and build actionable mechanistic insight, thereby opening the door to enhanced productivity. What M&S requirements must be satisfied to access and open the door, and begin reversing the productivity decline? Can current methods and tools fulfill the requirements, or are new methods necessary? We draw on the relevant, recent literature to provide and explore answers. In so doing, we identify essential, key roles for agent-based and other methods. We assemble a list of requirements necessary for M&S to meet the diverse needs distilled from a collection of research, review, and opinion articles. We argue that to realize its full potential, M&S should be actualized within a larger information technology framework--a dynamic knowledge repository--wherein models of various types execute, evolve, and increase in accuracy over time. We offer some details of the issues that must be addressed for such a repository to accrue the capabilities needed to reverse the productivity decline

Learning the lessons from the developed world: e-banking security in Nigeria

In the past decade banks invested heavily in internet technology so as to engage in e-business and e-commerce activities. However, this development exposed banks to threats, such as online fraud. Consequently, there was a need to adopt security measures and controls to mitigate such threats. Banks in developed countries have developed a level of ‘best practice’ to reduce such online threats. The objective of this study was to explore the extent to which banks in the developing world were benefitting from the experiences of banks in the developed world in terms of how they address online security threats. Case studies of two Nigerian Banks were undertaken using interviews and short questionnaire. The findings show respondents perceived the level of threats to e-banking in Nigeria to be low. When adopting e-banking security controls, the case study banks placed more emphasis on the technical dimension than the human dimension. Senior management commitment is a significant barrier to adopting best practice, which is highlighted in limited financial resources being provided for new investment in training or customer education. The study concludes that senior managers need to change their perceptions and priorities towards IT security to reduce the vulnerability of their e-banking services

Multimode interference devices for focusing in microfluidic channels

Low-cost, compact, automated optical microsystems for chemical analysis, such as microflow cytometers for identification of individual biological cells, require monolithically integrated microlenses for focusing in microfluidic channels, to enable high-resolution scattering and fluorescence measurements. The multimode interference device (MMI), which makes use of self-imaging in multimode waveguides, is shown to be a simple and effective alternative to the microlens for microflow cytometry. The MMIs have been designed, realized, and integrated with microfluidic channels in a silica-based glass waveguide material system. Focal spot sizes of 2.4 µm for MMIs have been measured at foci as far as 43.7 µm into the microfluidic channel

From Reunification to Economic Integration: Productivity and the Labor Market in Eastern Germany

macroeconomics, Reunification, Economic Integration, Productivity, Labor Market, Eastern Germany

What Explains the German Labor Market Miracle in the Great Recession?

Germany experienced an even deeper fall in GDP in the Great Recession than the United States with little employment loss. Employers’ reticence to hire in the preceding expansion - associated in part with a lack of confidence it would last - contributed to an employment shortfall equivalent to 40 percent of the missing employment decline in the recession. Another 20 percent may be explained by wage moderation. A third important element was the widespread adoption of working time accounts, which permit employers to avoid overtime pay if hours per worker average to standard hours over a window. We find that this provided disincentives for employers to lay off workers in the downturn. While the overall cuts in hours per worker were consistent with the severity of the Great Recession, reduction of working time account balances substituted for traditional government-sponsored short time work.unemployment, Germany, Great Recession, short time work, working time accounts, Hartz reforms, extensive vs. intensive employment margin

Industrial Electricity Demand for Turkey: A Structural Time Series Analysis

This research investigates the relationship between Turkish industrial electricity consumption, industrial value added and electricity prices in order to forecast future Turkish industrial electricity demand. To achieve this, an industrial electricity demand function for Turkey is estimated by applying the structural time series technique to annual data over the period 1960 to 2008. In addition to identifying the size and significance of the price and industrial value added (output) elasticities, this technique also uncovers the electricity Underlying Energy Demand Trend (UEDT) for the Turkish industrial sector and is, as far as is known, the first attempt to do this. The results suggest that output and real electricity prices and a UEDT all have an important role to play in driving Turkish industrial electricity demand. Consequently, they should all be incorporated when modelling Turkish industrial electricity demand and the estimated UEDT should arguably be considered in future energy policy decisions concerning the Turkish electricity industry. The output and price elasticities are estimated to be 0.15 and -0.16 respectively, with an increasing (but at a decreasing rate) UEDT and based on the estimated equation, and different forecast assumptions, it is predicted that Turkish industrial electricity demand will be somewhere between 97 and 148 TWh by 2020.Turkish Industrial Electricity Demand; Energy Demand Modelling and Forecasting; Structural Time Series Model (STSM); Future Scenarios.

A role for transcriptional repressor methyl-CpG-binding protein 2 and plasticity-related gene serum- and glucocorticoid-inducible kinase 1 in the induction of inflammatory pain states

Activity-dependent changes in neurons of the rat superficial dorsal horn are crucial for the induction and maintenance of neuropathic and inflammatory pain states. To identify the molecular mechanisms underlying this sensitization of superficial dorsal horn neurons, we undertook a genome-wide microarray profiling of dorsal horn gene transcripts at various times after induction of peripheral inflammation of the rat ankle joint. At early time points, upregulation of gene expression dominated, but by 7 d, downregulation was predominant. Two to 24 h after inflammation, we identified a small number of highly upregulated transcripts previously shown to be repressed by the Methyl-CpG-binding protein 2 (MeCP2), including serum-and glucocorticoid-inducible kinase (SGK1) and FK 506 binding protein 5, genes known to be important in experience-dependent plasticity. A decrease in expression of SIN3A, a corepressor in the MeCP2 silencing complex, was also found after inflammation. Phosphorylation of MeCP2 regulates activity-dependent gene transcription, and crucially we found that MeCP2 was phosphorylated in lamina I projection neurons 1 h after induction of peripheral inflammation. Lamina I projection neurons have been shown to be essential for the development of most pain states. SGK1 protein was also localized, in part, to lamina I projection neurons, and its expression in the superficial dorsal horn increased after inflammation. Furthermore, antisense knock-down of SGK1 delayed the onset of inflammatory hyperalgesia by 24 h at least. Our results uncover an unexpected complexity in the regulation of gene expression, including the modulation of transcriptional repression, that accompanies development and maintenance of an inflammatory pain state