Macromolecules, transient

Fast transient studies are largely focused on elementary kinetic processes in atoms and molecules, i.e., on unimolecular and bimolecular reactions with first and second order kinetics, respectively (although confonnational heterogeneity in macromolecules may lead to the observation of more complicated unimolecular kinetics). Examples of fast thennally activated unimolecular processes include dissociation reactions in molecules as simple as diatomics, and isomerization and tautomerization reactions in polyatomic molecules. A very rough estimate of the minimum time scale required for an elementary unimolecular reaction may be obtained from the Arrhenius expression for the reaction rate constant, k = A. The quantity /cg T//i from transition state theory provides... 

The inclusion of internal viscosity raises considerably the free-energy storage capacity of a rapidly deforming macromolecule as compared to the idealized Hookean spring model and could play a decisive role in mechanochemical reactivity in transient elongational flow. 

Under steady-state conditions, as in the Couette flow, the strain rate is constant over the reaction volume for a long period of time (several hours) and the system of Eq. (87) could be solved exactly with the matrix technique developed by Basedow et al. [153], Transient elongational flow, on the other hand, has two distinctive features, i.e. a short residence time (a few ps) and a non-uniform flow field, which must be incorporated into the kinetics equations. In transient elongational flow, each rate constant is a strongfunction of the strain-rate which varies with time in the Lagrangian frame moving with the center of mass of the macromolecule the local value of the strain rate for each spatial coordinate must be known before Eq. (87) can be solved. 

There are a few instances where a macromolecule in solution can be degraded even in the absence of an elongational flow field. In these circumstances, the chain scission was believed to happen in a partly extended state this situation is sufficiently related to the degradation in transient elongational flow to be worth... 

Most cells release macromolecules to the exterior by exocytosis. This process is also involved in membrane remodeling, when the components synthesized in the Colgi apparatus are carried in vesicles to the plasma membrane. The signal for exocytosis is often a hormone which, when it binds to a cell-surface receptor, induces a local and transient change in Ca concentration. Ca triggers exocytosis. Figure 41—16 provides a comparison of the mechanisms of exocytosis and endocytosis. 

This is the simplest of the models where violation of the Flory principle is permitted. The assumption behind this model stipulates that the reactivity of a polymer radical is predetermined by the type of bothjts ultimate and penultimate units [23]. Here, the pairs of terminal units MaM act, along with monomers M, as kinetically independent elements, so that there are m3 constants of the rate of elementary reactions of chain propagation ka ]r The stochastic process of conventional movement along macromolecules formed at fixed x will be Markovian, provided that monomeric units are differentiated by the type of preceding unit. In this case the number of transient states Sa of the extended Markov chain is m2 in accordance with the number of pairs of monomeric units. No special problems presents writing down the elements of the matrix of the transitions Q of such a chain [ 1,10,34,39] and deriving by means of the mathematical apparatus of the Markov chains the expressions for the instantaneous statistical characteristics of copolymers. By way of illustration this matrix will be presented for the case of binary copolymerization ... 

Essentially, in realistic polymer chains, a monomeric unit does not remember the way it appeared in the macroradical. All the experimental characteristics of a copolymer chemical structure are naturally described in terms of uncolored units. Consequently, having preliminarily calculated these characteristics in the ensemble of macromolecules with colored units, it is then necessary to erase colors bearing in mind that every state in a chain of uncolored units is an enhancement of a corresponding pair of states in a chain of colored units. The latter is the Markov chain with transient states (19), whose matrix of transitions looks as follows ... 

An exhaustive statistical description of living copolymers is provided in the literature [25]. There, proceeding from kinetic equations of the ideal model, the type of stochastic process which describes the probability measure on the set of macromolecules has been rigorously established. To the state Sa(x) of this process monomeric unit Ma corresponds formed at the instant r by addition of monomer Ma to the macroradical. To the statistical ensemble of macromolecules marked by the label x there corresponds a Markovian stochastic process with discrete time but with the set of transient states Sa(x) constituting continuum. Here the fundamental distinction from the Markov chain (where the number of states is discrete) is quite evident. The role of the probability transition matrix in characterizing this chain is now played by the integral operator kernel ... 

Normal biochemical events surrounding the maintenance and functions of the nervous system centers around energy metabolism, biosynthesis of macromolecules, and neurotransmitter synthesis, storage, release, uptake, and degradation. Measurement of these events is complicated by the sequenced nature of the components of the nervous system and the transient and labile nature of the moieties involved. Use of measurements of alterations in these functions as indicators of neurotoxicity is further complicated by our lack of a complete understanding of the normal operation of these systems and by the multitude of day-to-day occurrences (such as diurnal cycle, diet, temperature, age, sex, and endocrine status) which are constantly modulating the baseline system. For detailed discussions of these difficulties, the reader is advised to see Damstra and Bondy (1980, 1982). 

The particularity of the LIT-orbitrap instrument is the independent operation of the orbitrap and the LIT. Because high resolution requires longer transient time, further data can already be collected in the LIT at the same time. As an example accurate mass measurements of the precursor ion can be performed in the orbitrap while MS and MS spectra are recorded with the linear ion trap. The LIT-orbitrap has less resolution than a FT-ICR instrument with similar duty cycle, but its maintenance costs are far lower than for the FT-ICR. Both instruments will have a major impact in mainly qualitative analysis of low molecular weight compounds and macromolecules. 

To eliminate the threat of shock, replenishment of the circulation is essential. With moderate loss of blood, administration of a plasma volume expander may be sufficient Blood plasma consists basically of water, electrolytes, and plasma proteins. However, a plasma substitute need not contain plasma proteins. These can be suitably replaced with macromolecules ( colloids ) that like plasma proteins, (1) do not readily leave the circulation and are poorly filtrable in the renal glomerulus and (2) bind water along with its solutes due to their colloid osmotic properties. In this manner, they will maintain circulatory filling pressure for many hours. On the other hand, volume substitution is only transiently needed and therefore complete elimination of these colloids from the body is clearly desirable. 

A X-ray crystallographic method for detecting the transient accumulation of intermediates in enzyme catalysis, protein folding, ligand-binding interactions, and other processes involving macromolecules. The approach is premised on the well documented retention of substantial reactivity of biological macromolecules, even in the crystalline state. 

Tanaka F, Edwards SF. Viscoelastic properties of physically cross-linked networks—transient network theory. Macromolecules 1992 25 1516-1523. 

X-ray crystallography is the method of choice for determination of structures of large macromolecules such as proteins. Nowadays, roughly 48,000 x-ray structures are stored in the Protein Data Bank (http //www.rcsb.org Berman et al. 2000). X-ray crystallography is traditionally a static method, i.e., without time resolution. In order to follow the kinetics and to determine the structure of the transiently occupied intermediate states of proteins, time-resolved crystallography has to be used (Moffat 1989). The time resolution, has to be as good as for any other method employed to follow reaction kinetics. This implies that x-ray data must be collected as fast as possible. 

Reactive chemicals or their reactive intermediates, such as free radicals and other electrophilic species, may form essentially irreversible covalent bonds with adjacent macromolecules, such as proteins, lipids, and DNA, resulting in the formation of adducts. Covalent adducts can disrupt the normal function of such macromolecules and result in a broad spectrum of toxic responses. These may range from localized transient skin irritation to systemic target organ toxicity (such as hepatotoxicity, neurotoxicity, and renal toxicity), genotoxicity, or carcinogenicity. 

Our work aims at identifying, by subpicosecond broadband transient absorption and gain spectroscopy, the primary photochemical steps of the phototransduction process in Blepharisma japonicum, more specifically in the light-adapted form of the organism (blue cell) for which the photoactive pigment is oxyblepharismin [5] (see Scheme 1) and the associated macromolecule is a large non-soluble protein (200 kDa) [6]. 

Recently another electrically assisted drug delivery technology, electroporation, was proposed as an alternative or adjuvant to iontophoresis. Electroporation comprises the use of electric pulses to induce transient changes in the cell membrane architecture that turn it into more permeable barrier. Beside the permeabilization effect on cell membrane, it was postulated that this technique induces electrophoretic effect on charged macromolecules and drives them to move across the destabilized membrane [205]. 

Chemical PEs have recently been studied for increasing transdermal delivery of ASOs or other polar macromolecules [35]. Chemically induced transdermal penetration results from a transient reduction in the barrier properties of the stratum corneum. The reduction may be attributed to a variety of factors such as the opening of intercellular junctions due to hydration [36], solubilization of the stratum corneum [37, 38], or increased lipid bilayer fluidization [39, 40]. Combining various surfactants and co-solvents can be used to achieve skin penetration, purportedly resulting in therapeutically relevant concentrations of ASO in the viable epidermis and dermis [41]. In summary, it appears feasible to deliver ASO to the skin using a number of different delivery techniques and formulations. 

A.W. Chow, and G.G. Fuller, The rheo-optical response of rod-like chains subject to transient shear flow. Part I Model calculations on the effects of polydispersity, Macromolecules 18, 786 (1985) A.W. Chow, G.G. Fuller, D.G. Wallace and J.A. Madri, The rheo-optical response of rod-like chains subject to transient shear flow. Part II. Two-color flow birefringence measurements, Macromolecules 18,793 (1985) A.W. Chow, G.G. Fuller, D.G. Wallace and J.A. Madri, The rheo-optical response of rod-like shortened collagen protein to transient shear flow, Macromolecules, 18, 805 (1985). 

K. Hongladarom and W. R. Burghardt, Molecular alignment of polymer liquid crystals in shear flows. 2. Transient flow behavior in poly(benzyl glutamate) solutions, Macromolecules, 26,785 (1993). 

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