The Point of No Return

It should be emphasized that isomerization is by no means the only process involving chemical reactions in which spectroscopy plays a key role as an experimental probe. A very exciting topic of recent interest is the observation and computation [73, 74] of the spectral properties of the transition state [6]—catching a molecule in the act as it passes the point of no return from reactants to products. Furthennore, it has been discovered from spectroscopic observation [75] that molecules can have motions that are stable for long times even above the barrier to reaction. 

The experimental conditions, even though under a controlled laboratory environment, are not too different from what may be observed in a closed drum of this material exposed to ambient temperatures for prolonged periods of time. This paper emphasizes that using only the onset of an exotherm as an indication of the point of no return for a reactive chemical system may be insufficient, as pressure may accumulate even at temperatures much lower than the anticipated exotherm. 

Figure 4. Outline of the cellular respose to ionizing radiation. 1.Early changes induced by radiation. 2. Adaptive response. 3. Initiation of apoptosis. 4. Execution of apoptosis. S. Late phases of apoptosis. The point of no return from death is the transition hum 3 to 4.

Obviously the best treatment for cirrhosis is removal of the injurious event. In the case of viral hepatitis, viral load can at least be temporarily reduced with anti-viral agents such as lamivudine, ribavirin and/or IFNa [76]. Unfortunately, complete removal of the injurious event is frequently not possible. Moreover, by the time cirrhosis is diagnosed the fibrotic process has usually progressed beyond the point of no return and removal of the injurious event will have little effect. Successful pharmacological treatment to reverse the fibrotic... 

We distinguish two limiting cases dissociation through a narrow transition state and dissociation through a wide transition state where we define the region that separates the reactants and the products (i.e., the point of no return ) as the transition state. The first case may be qualitatively considered as a direct process with the ultimate dissociation starting at the transition state. The second case may be treated by statistical methods without including dynamical constraints. We will discuss both limits separately and illustrate them with typical examples. 

Figure 16.2. Reversible versus irreversible cell injury. Depending on the cell and/or tissue type and the relative health of the individual, cells may adapt to stress within a limited range of homeostatic ability. If cell injury exceeds this range, the point of no return is reached (irreversible injury) and the cell dies. Note that cell death and the degradative changes associated with necrosis are at different time points.

Currently, the precise biochemical events initiating irreversible cell injury are unknown. At what stage did the cell actually die What is the critical biochemical event responsible for the point of no return There is no universally accepted biochemical explanation for the transition from reversible injury to cell death. The duration of hypoxia necessary to induce irreversible cell injury varies according to cell type and its nutritional and hormonal status ... 

Green DR, Amarante-Mendes GP (1998) The point of no return mitochondria, caspases, and the commitment to cell death. Results Probl Cell Differ 24 45-61 Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305 ... 

The effector caspases (caspase-3, caspase-6, caspase-7) are responsible for the morphological and biochemical changes that mark apoptosis. Activation of the effector caspases occurs via cleavage of the proform by activated initiator caspases and often marks the point of no return for cell death. Substrates for effector caspases include the caspases themselves (autoactivation), cytoskeletal components (i.e., actin, fodrin, and cytokeratins), poly (ADP-ribose) polymerase (PARP), and nuclear matrix proteins like Lamin B. Detection of caspase-3 expression by immunohistochemistry has been studied extensively due to its apical position in the effector caspase cascade (7-9,11-16). As with the initiator caspases, it is important to determine which form of the enzyme is recognized by the spe-... 

If, then, product choice seeks to fill needs, it follows that careful market appraisal to confirm the original judgment will be required before the program gets beyond the point of no return. We expect that successful market development of organic chemicals in the sixties will in this manner be strongly directed toward specific markets even more than in the past. 

Step 4. Adsorbed gas molecules or fragments form an intermediate complex on active surface sites. This short-lived intermediate, called the transition state, represents the point of no return for reactants along the reaction pathway. 

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