Interconnects early developments

The PBPK model for a chemical substance is developed in four interconnected steps (1) model representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan and Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 1994 Leung 1993). PBPK models for a particular substance require estimates of the chemical substance-specific... 

Once past the discovery and initial development stages, the safety assessment aspects of the process become extremely tightly connected with the other aspects of the development of a compound, particularly the clinical aspects. These interconnections are coordinated by project management systems. At many times during the early years of the development process, safety assessment constitutes the rate-limiting step it is, in the language of project management, on the critical path. 

The modern electronics era began at Bell Telephone Laboratories in 1948 with the invention of the solid-state transistor, which replaced the large thermionic vacuum tube, the mainstay of the electronics industry for the previous 40 years. Transistors were smaller and much more robust than their vacuum tube counterparts and required much less power to operate. Electronic circuits of the 1950s and early 1960s were assembled from discrete transistors, diodes, and resistors, for example, but rapid advances in circuit complexity and density, driven by developments in computer technology, soon led to an impasse, namely, how to approach the problem of interconnecting hundreds, perhaps thousands, (some visionaries would have said millions) of discrete devices into a complex circuit. 

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