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Uncertainty regarding size of cell population and rate of cell duplication is taken into account in a model which describes quantitatively the experimental induction of cancer by ultraviolet radiation. Quantitative relationships indicate that overall cell population growth is governed by feedback control of metabolite supply. Application of the model to other kinds of carcinogen, design of experiments, and implications regarding cancer mechanisms are considered.

The time dependence of oxygen consumption of actively respiring mitochondria has been studied in detail as adenosine diphosphate (ADP) becomes depleted, and the dependence on exogenous adenosine triphosphate (ATP) and orthophosphate (Pi) has been investigated. The results are consistent with a model having the electron transport and phosphorylation processes in chemical equilibrium with the extramitochondrial phosphorylation state, [ATP] [ADP] [Pi], and the respiration rate proportional to the concentration of reduced cytochrome a3. The latter is, in turn, dependent upon the phosphorylation state. The mathematical shape of polarographic oxygen consumption curves between the region of excess ADP and the region of minimum ADP has been calculated from the model, and agreement has been found with the experimentally measured rates of oxygen consumption during ADP depletion.

Observed frequencies of restriction enzyme cleavage in viral DNAs are compared to those expected from the cleavage site sequence and the known size and nearest neighbour frequencies of the DNAs. It is found that a number of significant deviations from expectation occur, and possible explanations are put forward.

The nonionic detergent Brij 58 eliminates irreversibly the capability of the sarcoplasmic reticulum (SR) of skinned crayfish muscle fibers to sequester Ca and to release it under appropriate stimulation. In contrast to deoxycholate (DOC) which causes an irreversible diminution of tension as well, Brij 58 does not affect the contractile proteins. Comparison of the time-course of tension development before and after Brij treatment demonstrates that Ca is accessible to the contractile proteins more rapidly after the SR is destroyed but, nevertheless, much more slowly than is predicted for free diffusion of Ca in the myoplasm. Slowing apparently results because of the presence of ca 1 mmol/kg fiber of myoplasmic Ca-binding sites that remain after Ca uptake of the SR is eliminated. A theoretical model is presented which allows for the effects of binding sites and of an unstirred layer in the vicinity of the fiber on Ca diffusion into the myoplasm.

Enzymatic activities involved in the transformations of uridine nucleotides by intact erythrocytes and their subfractions have been studied and the following enzymatic activities have been identified: UTPase, UDPase, UMPase and uridylate kinase. UTPase activity was present exclusively in the stromal fraction while UMPase and uridylate kinase activities were specific in the soluble fraction. UDPase was present in both the stromal and soluble fractions. This compartmentation in erythrocytes differs from that reported for the enzymes involved in adenine nucleotides transformations. Due to its sensitivity to Zn2+, uridylate kinase could be differentiated from adenylate kinase.

An eight-compartment model was developed for the pharmacokinetics of D-penicillamine. The analysis shows that a simpler model, based on the assumption of one chemical form of penicillamine only, fails and that the concept of two different forms of penicillamine must be introduced. Most probably, it concerns the disulfide of penicillamine and its mixed disulfide with cysteine. The primary distribution volume for both compounds is the extracellular fluid. Binding to plasma proteins has no essential effect on the overall kinetics. The two disulfides are handled by the kidneys in a different manner.

1. 1 The transfer of the dyestuff probe, methyl orange, from an aqueous phase into phospholipid-cholesterol micelles in an adjacent organic phase was found to be affected by testosterone quite differently than by dihydrotestosterone. The kinetics of transport of the probe proved extremely dependent in the presence of dihydrotestosterone upon the extent of prehydration of the organic phase. Rates were measured at controlled temperatures from 19 to 45 °C. 2. 2 For the system, lecithin-cholesterol-testosterone at selected concentrations, high rates of transfer of methyl orange were observed between 23 and 35 °C. Below 22 and above 36 °C, the transport rates were reduced to those observed with lecithin alone. 3. 3 For the corresponding system containing dihydrotostesterone the transition at 35 °C was essentially the reverse of that for the system containing testosterone. Low rates were observed below 35 °C, elevated rates above this temperature.

Sebum is the excretory product of the sebaceous glands. These glands are found in the s kin of all mammals excep~ whales and porpoises (Montagna. 1963). The bulk of sebu m is a mixture of relative ly nonpolar lipids, most of which are synthesized d e novo by the gland. The lipid is excreted by a "holocrine mechanis m , whereby the lipid-laden cells dis integrate and pour their content s through the sebaceous duct onto the s kin s urface. One apparent function of sebum is to provide the s kin surface and hair with a hydrophobic coating. The preen gland of birds has a s imilar func tion, but it is not a sebaceous gland . The preputial glands of rodents are s pecialized sebaceous glands, used primarily for the re lease of pheromones. The c hemistry of sebum is interesting, because many compounds not found elsewhere i.n the body have been identified in sebum . As firs t was clearly shown by Wheatley (1956). the compos ition of sebum is remarkably species s pec ific. The application of modern chromatographic methods to studies of sebum has greatly expanded our knowledge of its chemis try during the last two decades. There have been some comparative s tudies (Wheatley and J a mes, 1957; Nicolaides et al.. 1968. l970; Nikkari, 1969), but in m ost studies each investigator has worked on one s pecies only. The present review s ummarizes the results of different authors in a form that allows easier compa rison among various species.

A method is described for analyzing skin impedance data and applied to the determination of a steady-state electrical model for intact human skin. An algorithm is presented for the analytical procedure, Bode analysis, and a sample impedance function is obtained. Bode plots are employed to synthesize a passive equivalent circuit from sample measurements of “black box” skin impedance magnitude and phase angle, and representative values for the circuit elements are presented.

A criterion is proposed which must be met in order to demonstrate that two different proteins are required for the initiation of DNA synthesis, with each protein being synthesized at a different time prior to initiation, and with the synthesis of each protein having a different sensitivity to inhibition by chloramphenicol. Specifically, as the CM concentration is continuously varied, there must be a discontinuous variation in the number of origins able to be initiated at each concentration. In the light of this criterion, I suggest that there is no mm evidence for the proposal that there exist two different proteins which are required for initiation of DNA replication in Escherichia coli.

An exact expression for the solvent diffusion coefficient in a pore that is so narrow that two molecules cannot get around each other is derived. The theory states that the diffusion coefficient for a pore that contains n molecules is simply equal to the diffusion coefficient a molecule would have if it were all alone in the pore ( D °) divided by n . The theory is very general. Two different models that can be used to determine D ° are described. An exact experimental test of the theory is carried out by the use of computer simulation (molecular dynamics). It is shown that as long as the density of molecules in the pore is not too high, the experimental results are not significantly different from the theoretical preditions. These experimental results also test the theory presented in the first paper of this series and provide strong support for those results.

The thermodynamic formulation of isotope interaction (coupling of abundant and tracer isotope flows) has been tested in a highly permselective anion exchange membrane in the absence of significant electroosmosis. A previous study of Cl− permeation has now been extended to include permeation of I−, Acetate, and SO 4 2− in different bath concentrations, with the use of both electrical and chemical driving forces. The flux ratios were “abnormal” according to the usual criteria for simple passive flow, but were closely predicted by the theoretical expression incorporating the influence of isotope interaction. In the absence of coupled flows of other chemical species the extent of isotope interaction can be determined either from the flux ratio or from the measurement of a single unidirectional flux at two settings of the electrochemical potential difference. Direct evidence of negative isotope interaction was presented.

The behavior of a number of motile flagellated bacteria toward viscosity characteristics of their fluid environments was observed. All showed an increase in velocity (micrometers per second) in more viscous solutions. Velocity reached a maximum at a characteristic value, however, and thereafter decreased with higher viscosities. Peritrichously flagellated bacteria had maximum velocities at higher viscosities than polarly flagellated bacteria. Effects of temperature, and possible utilization of chemical constituents in the viscous solutions, were studied and found to be negligible factors under the experimental conditions used. Different agents produced the same phenomenon, thus indicating that there probably were no chemically induced metabolic effects. Loss of available water and the possibility of a variable energy supply to the flagellar propulsive system were considered but are believed minimal. Theoretically derived thermodynamic equations were utilized and suggest that the conformation of the flagellar helix affects efficiency of propulsion. Such a relationship between helix waveform and velocity was experimentally observed with Thiospirillum jenese .

A constitutive equation for parallel-fibered elastic tissue is developed in the form of a non-linear hereditary integral. Material constants were determined from relaxation tests and these were used in the constitutive equation to predict results of constant strain rate tests, hysteresis loops and sinusoidal tests. Test speciments were obtained from the ligamentum nuchae of gross bovine specimens.

Isolated male Wistar rats exhibited muricide, friendly or indifferent behavior when exposed to mice. Rats from each category were treated with α-methyl-p-tyrosine, 6-hydroxydopamine and electrolytic lesion of the midbrain-raphe nucleus and reexposed to mice at regular intervals. Aggregated control rats were treated similarly. All three treatments rendered the indifferent rats more reactive and aggressive after 6-hydroxydopamine and midbrain-raphe lesion. The friendly rats became less reactive post-treatment, then recovered, but never exhibited aggression. The muricide rats were virtually unaffected by any treatment. A third of the aggregated control rats showed aggressive and muricide behavior both after 6-hydroxydopamine and midbrain raphe lesions.

It will be my intention to compare established and recently proposed models for . genetic recombination, with special attention to the separate component principles they contain and the function ofthese principles in the various models. As increasing attention has been paid to realistic details of DNA structure and enzymology, recombination models have become molecular ones, sufficiently detailed that such a comparison may be useful to enable us to view experimental results in this area in a variety of different lights. There is no conceptual distinction separating the ideas concerning DNA recombi­ nation in microorganisms and those concerning genetic recombination in general. Recombination in higher organisms principally occurs during meiotic events highly organized through evolution and therefore relatively refractory to experimental intervention. In these forms the reproductive cycles are often long, large postmeiotic populations may be cumbersome to deal with, and the genetic fine structure can

A “complete” and quantitative kinetic model for the states and transitions of the barnacle visual pigment in situ has been constructed from intracellular recordings of the early receptor potential responses to long light pulses. The model involves two stable and four thermolabile states and 10 photochemical, thermal, and metabolic transitions among them. The existence of each state and transition is demonstrated by qualitative examination of the response resulting from a carefully chosen experimental paradigm (combination of intensity, duration, and wavelength of adaptation and stimulation). Quantitative examination of the same responses determines all of the model transition rates, but only puts constraints on the state dipole moments. The latter are determined, and the former refined, by quantitative comparison of the predictions of the complete model with the responses to a set of paradigms chosen to involve as many states and transitions as possible. The fact that good fits can be obtained to these responses without further modification of the model supports its completeness.

The mechanism of activation of alkaline phosphatase (EC 3.1.3.1) from pig kidney by Mg2+ ions was investigated with the aid of kinetic measurements. Mg2+ ions are essential for enzyme activity. The following model (Scheme 1 of the text) for the reaction of enzyme, substrate and Mg2+ ions was derived: [Formula: see text] The binding of the substrate to the enzyme is independent of the binding of the activator, and vice versa. Mg2+ must therefore play a part in the substrate decomposition. It is not possible to determine whether the Mg2+ ions are involved directly in the catalytic process, or whether they act as regulatory effectors. Because of the strong affinity existing between the alkaline phosphatase and Mg2+, it is necessary to adjust the metal-ion concentration with the aid of a metal buffer. In the Appendix the necessary equations are derived for calculating the concentration of free metal ions in a system with several different metal ions. A FORTRAN IV program for solving these equations and for graphic presentation of the results has been deposited as Supplementary Publication SUP 50030 at the British Library (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS 23 7 BQ, U.K., from whom copies may be obtained on the terms indicated in Biochem. J. (1973), 131, 5.

By means of absorption spectroscopy we show that in benzene solutions, only one molecule of 2-methylimidazole is bound with a great affinity by deuteroheme (K = 1.25 10 4 M −1 ) and mesotetraphenylheme (K = 2.4 10 4 M −1 ). Besides, two overlapping steps may be distinguished when hemes bind imidazole molecules. The equilibrium constants are K 1 = 4.5 10 3 M −1 and 8.8 10 3 M −1 , K 2 = 6.8 10 4 M −1 and 7.9 10 4 M −1 for deuteroheme and mesotetraphenylheme respectively.

Classical enzymology ignores the role which cellular membranes may play in regulating reaction kinetics in vivo. The correct description of cellular metabolic processes must derive from a mass balance equation for each reacting species. An elementary mathematical model, called the “continuous flow stirred tank reactor” in the chemical engineering literature, has been applied to Michaelis-Menten kinetics, substrate inhibition kinetics, and kinetics involving hydrogen ion as a hyproduct. A number of remarkable phenomena, including multiple stationary states, threshold effects, temporal patterns, homeostatic regulation, amplification, and irreversible differentiation can result. Predictions of the model are in qualitative accord with experimental and theoretical studies of insolubilized enzymes, which are conventionally modeled by a more difficult mathematical formalism.

A hypothesis to explain RNA degradation in Escherichia coli is proposed. In this hypothesis all classes of RNA are potentially degradable unless they are protected. The proposed mechanism for mRNA degradation requires a combination of endonuclease(s) and exonuclease(s) which degrades RNA in the 3′ to 5′ direction. Ribosomes attached to the newly synthesized 5′ end of an mRNA molecule protect it from being attacked endonucleolytically; a delay in attachment of ribosomes to this end exposes it to endonucleolytic cleavage, followed by exonucleolytic digestion from the newly exposed 3′ end to the 5′ end. This mechanism is consistent with an overall 5′ to 3′ direction of degradation for mRNA. Exoribonucleases that degrade polyribonucleotides from the 5′ end to 3′ end are not required. The 3′ end of the messenger is protected by its association with DNA. In order to enable the mRNA to remain anchored to the DNA while serving as an efficient template for protein synthesis, a special region near the 3′ end of the mRNA is envisaged. This hypothetical region would not be translated.

A theoretical analysis provides a means to estimate the blood flow into a branch from a measurement of the pressure drop from the main stream into the branch, and the ratio of the width of the branch to that of the main vessel. It shows that in the ordinary circumstance in which the diameter of the branch is one-half that of the trunk or smaller, a large drop of pressure from the main stream to the branch is expected. Such a pressure drop would be particularly accentuated if there is a local narrowing in the branch such as a sphincter.

A computer model for excitation-contraction coupling in mammalian cardiac cells was designed based on calcium movements in a multicompartment system. The model includes an extracellular space of constant calcium concentration from which calcium crosses the membrane and reaches the myoplasma by a voltage and time dependent process. The free myoplasmic calcium content is considered to reflect the intensity of the active state. Calcium can be taken up either by a carrier-sustained two step reaction into a compartment representing some parts of the longitudinal system or into another pool representing mitochondria. Calcium can leave the cell or can be released again into the myoplasma by a second order reaction. The behaviour of the model is compared to that of living cardiac ventricular muscle. The model correctly predicts the following groups of inotropic phenomena. Steady state and dynamic force-frequency relationships, positive and negative staircases after both changes of frequency and AP-duration, mechanical transients after a period of rest and aftercontractions.

A Markov process (chain) of gene frequency change is derived for a geographically-structured model of a population. The population consists of colonies which are connected by migration. Selection operates in each colony independently. It is shown that there exists a stochastic clock that transforms the originally complicated process of gene frequency change to a random walk which is independent of the geographical structure of the population. The time parameter is a local random time that is dependent on the sample path. In fact, if the alleles are selectively neutral, the time parameter is exactly equal to the sum of the average local genetic variation appearing in the population, and otherwise they are approximately equal. The Kolmogorov forward and backward equations of the process are obtained. As a limit of large population size, a diffusion process is derived. The transition probabilities of the Markov chain and of the diffusion process are obtained explicitly. Certain quantities of biological interest are shown to be independent of the population structure. The quantities are the fixation probability of a mutant, the sum of the average local genetic variation and the variation summed over the generations in which the gene frequency in the whole population assumes a specified value.

Identification of chloroplast coupling factor particles, by the freeze-etching and negative-staining techniques, was made utilizing chloroplast thylakoids isolated from spinach leaves. Complete removal of particles, comparable in diameter to purified coupling factor particles, from the outer surface of freeze-etched thylakoids was achieved by treatment with 0.8% silicotungstate. Reappearance of particles, comparable in diameter to purified coupling factor particles, on the outer surface of freeze-etched thylakoids was demonstrated by combining silicotungstate-treated thylakoids with purified chloroplast coupling factor. Negative-staining results were in agreement with the freeze-etch data. The results demonstrate that the chloroplast coupling factor particles are exposed on the outer surface.

When two species compete with each other, one is likely to displace or exclude the other. Several circumstances under which they may coexist indefinitely have been presented in the literature; the present contribution presents examples of one more. Under circumstances where both populations are repeatedly decreased (for example because of annual environmental changes) then subsequent to each decrease both species grow unrestrictedly and then interact with each other in a competitive fashion. If the species that grows more rapidly under unrestricted conditions is at a disadvantage during competitive phases of growth, this effect prolongs coexistence but may not prevent eventual extinction of one or the other species. However, it is shown that there are certain broad ranges of conditions for population growth that lead to permanent cyclical stability. The stability described here is such that the ecosystem will return to the same dynamic balance even when severely perturbed. It is also shown that this kind of stability can be either favored or prevented in certain cases by random fluctuations in the environment affecting season length, kill factor, etc.

When the complexity of a developmental system evolves to a certain point, appreciable variation must occur in the process. The problem the biologist faces is whether this point constitutes a limit to the evolution of complexity in developmental systems. If not, what mechanisms are employed to cope with the problem ? The problem—essentially one in “custom fitting” of parts, — and the possible solution(s) to it that have evolved are discussed. The antibody producing system appears to be one that “solves” the custom-fitting problem.

A set of equations has been derived to describe the distribution of intracranial pressure and tension during the development of acute obstructive hydrocephalus. Theoretical predictions correlate with clinical and pathological observations. Biomechanical and experimental considerations indicate that in the first few hours after acute outflow obstruction, the ventricles expand at the expense of easily-displaced intracranial fluid compartments, and destructively high brain tension is concentrated in periventricular areas. Once displaceable fluids are exhausted, the rigidity of the skull becomes the dominant factor. If the skull is rigid, brain tension drops to very low values, intracranial pressure becomes uniform, and ventricular expansion is essentially halted. If the skull is soft and plastic, as in an infant, brain tension remains high and ventricular expansion continues, though its course may eventually be modified by pressure changes and by the geometric factors illustrated in Fig. 4. Experimentally, this formulation seems accurate for adult mammals. The clinical course of infants with hydrocephalus is well known; but Epstein, Hochwald and Ransohoff (1973) have recently shown that restrictive head bandaging will prevent skull expansion and limit neurological damage in infants as well. There is little reason to suppose that the mechanical forces in normal-pressure hydrocephalus are substantially different, despite the presence of free communication between the ventricular system and the lumber subarchnoid space.

1. The dispersion of solutes in plasma and blood has been studied by observing the clearance at a point down-stream of a bolus of labelled solution by the steady flow of unlabelled solution.2. With a low molecular weight solute the clearance curve is qualitatively similar in 2N-KCl solution, plasma and whole blood.3. The dispersion of a high molecular weight protein, [(131)I]HSA, in plasma is dominated by the velocity profile of the flow.4. The clearance curves for HSA in whole blood are similar to those of plasma, except that the red blood cells speed the clearance of protein in the tail region of the curve.5. An analysis of the data suggests that the dispersion of solutes during blood flow through a straight tube can be attributed to the combined effects of solute diffusion and laminar convection. There is no evidence that induced motion of the erythrocytes produces significant mixing, in the bulk of the flow.

Summary. When data-points on the descending phase of autoendogenous plasma [75Se]selenomethionine-fibrinogen (75SeM-fibrinogen) radioactivity curves in rabbits were expressed as per cent of maximum radioactivity, they could be fitted to single exponential curves both in controls and in animals with enhanced fibrinogen synthesis from multiple causes. Intravascular half-disappearance times (HDTs) determined from these slopes were inversely related to maximum per cent incorporation of 75SeM into fibrinogen (r= 0.662, P

Guberan, E. and Fernandez, J. (1974).British Journal of Industrial Medicine,31, 159-167. Control of industrial exposure to tetrachloroethylene by measuring alveolar concentrations: theoretical approach using a mathematical model. The uptake, distribution, and elimination of tetrachloroethylene were studied using a mathematical model, and predicted alveolar concentrations were compared with experimental data. Because of its high fat solubility the solvent accumulated in adipose tissue with a predicted biological half-life of 71·5 hours. The relation between the alveolar concentrations and the level or duration of exposure was discussed. The alveolar concentrations of tetrachloroethylene during and after similar exposure were predicted in subjects who differed in age, body weight, height, and body fat content, both at rest and during physical effort. Predictions were made of the alveolar concentrations following exposures to steady and variable concentrations in ambient air, and following exposures of several weeks of the type occuring in industry. It was concluded that measurement of the postexposure alveolar concentrations could be used to estimate the mean exposure to tetrachloroethylene in most industrial situations.

X-ray diffraction measurements show that the beta'-crystalline to liquid crystalline transitions of dipalmitoyl lecithin-water mixtures take place over temperature ranges of several degrees, and by the gradual disappearance of one crystalline state accompanied by the gradual appearance of the other. The narrowness of the low angle X-ray lines indicates that the two crystalline states exist in separate phases. At a given temperature, the liquid crystalline phase has the greater water content. The bilayers of the liquid crystalline phase are thinner than those of the beta'-crystalline phase while the distances between bilayers are essentially equal in the two phases.

The lateral expansion in dipalmitoyllecithin-cholesterol multibilayer films has been investigated using interacting pairs of cholestane spin labels. The abrupt lateral expansion occurring in dipalmitoyllecithin at the phase transitio has been directly demonstrated, as also has the extremely high lateral expansivity occurring in the region of lateral phase separation of dipalmitoyllecithin-cholesterol bilayers. A higher lateral expansivity is found above the dipalmitoyllecithin phase transition than below it. The measured increase in lateral molecular separation at the phase transition correlates well with the change in X-ray short spacing, and also with other, indirect, dimensional measurements on the change in area per molecule in the bilayer. Cholesterol is found to have opposite effects on the lateral molecular packing in dipalmitoyllecithin bilayers above and below the phase transition. These opposing effects are also manifest in a reduction, with increasing cholesterol composition, of the total lateral expansion over the transition region. The measured lateral separations are used to calculate the decrease by cholesterol of the intermolecular contribution to the latent heat absorbed over the transition region. The calculations are consistent with the calorimetric measurements of the total latent heat. These results suggest that the observed decrease in the calorimetric onset temperatures for lateral phase separations could be attributed to the decreased lateral expansion in the bilayers containing cholesterol. The broadening of the transition region could also be correlated with a decrease in the cooperativity of intermolecular interactions resulting from the increased intermolecular spacing induced by cholesterol below the transition.

A cholestane spin probe was used to study the effects of the all- trans isomers of retinal and retinol, and the 13- cis - isomer of retinal on the degree of organization of oriented phospholipid multibilayer model membranes in the dark. Concentration-dependent effects were observed indicative of changes in the degree of organization of phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, sphingomyelin, and brain lipids. In general the all- trans compounds improved the degree of order of the lipid films at low concentrations, and decreased it at high concentrations. The 13- cis retinal served only to decrease the degree of order. The magnitudes of these effects depend on lipid composition and the nature of the pigment polar residue. Chemical as well as nonbonding interactions are considered to be responsible for these various effects.

Measurements of the steady state polarization of fluorescence from perylene and 9-vinylanthracene embedded in bilayer membranes were performed as a function of temperature. Similar measurements were made when these probes were dissolved in hydrocarbons as model solvents. The effects of cholesterol and n-alkyl alcohol additions to bilayers and head group variation were also examined. Results were expressed in terms of the average rotation rates of the probes. At 25°C, the calculated rotation rate for perylene in egg phosphatidylcholine vesicles was 275 × 106 sec−1 as compared to 2400 × 106 sec−1 for perylene in n-hexadecane. However, the activation energies for probe rotation in both environments was about 7 kcal/mole suggesting similar rotational diffusion mechanisms. Membrane microviscosity evaluations were performed according to a recently published scheme and an assessment of this method of viscosity estimation was given. The presence of an approximately equimolar amount of cholesterol impeded probe rotation (90 × 106 sec−1 at 25°C) and reduced the activation energy (4.9 kcal/mole) for probe rotation. In contrast, addition of n-alkyl alcohols to the vesicle suspension acted to increase probe rotation rates, an indication of fluidization of the membranes. This is in accord with spin label and cation permeability data for similar membranes. It was concluded that this method of probing can adequately report changes in membrane dynamic structure when these changes occur uniformly over the membrane surface. The interpretation is less clear when structural changes occur only in patches or domains of the membrane thereby producing a non-uniform surface distribution of probes.

A multi-locus model for complete positive assortative mating is discussed. For a two-locus model, if the gene frequencies for the two loci are different, as they are likely to be, it is shown that in equilibrium the population is not composed of only two homozygous types, as is usually thought. The limiting distribution will have three homozygous genotypes depending upon the initial gene frequencies. If there are m-loci such that gene frequencies at all loci are different, there will be (m+1) such homozygous genotypes present in the equilibrium population, one in each phenotypic group.

Vasopressin causes a decrease in electrical resistance of phosphatidylserine bilayers. The magnitude of the decrease is a function of vasopressin and salt concentrations. The conducting channel is produced probably by aggregation of 4–5 molecules of the hormone.

A description is given of a slide rule which determines the relative concentrations of enzyme-containing intermediates appearing in an enzyme catalysed reaction whose mechanism involves not more than six such intermediates.

A transient-phase method is described for obtaining values for the individual rate constants of a single-substrate two-intermediate enzyme mechanism. In principle, values of k 1 , k −1 and k 3 can be obtained from such studies, as can values of inhibition constants k q and k −q from studies of a competitively-inhibited reaction. An experimental stopped-flow study is made for the α-chymotrypsin-catalyzed hydrolysis of p- nitrophenyl acetate, in the absence and presence of the inhibitor indole, and the results are consistent with the theoretical predictions. Values of k 1 , k −1 , k 2 and k 3 were obtained. The transient-phase equations for many enzyme systems, at limiting enzyme concentration, are in all cases of the form. x = vt + β + ∑ i=1 n β i e − λ i i where n , the number of exponential terms, is equal to the number of enzyme-containing intermediates in the mechanism (not counting the free enzyme). The sum of the exponents λ, i.e. ∑ i=1 n , is equal to the sum of all of the first-order rate constants, plus the sum of all the second-order rate constants each multiplied by the corresponding substrate or modifier concentration: ∑ i=1 n λ i = ∑ i k i c i + ∑ j k j where k i is a second-order rate constant and k j a first-order constant. This suggests general procedures for obtaining rate constants. Published results on α-chymotrypsin and alkaline phosphatase are reinterpreted in the light of the theory.

This paper points out certain theoretical problems in DNA synthesis associated with antiprimer transcription and with circularization that could oblige RNA tumor viruses to rely on a polyploid genome. It is suggested that each completed act of reverse transcription may be coupled with an act of genetic recombination aimed at recovering the antiprimer information from an adjacent genome subunit in a polyploid train. A partially double-stranded DNA transcript could then be formed with sufficient terminal redundancy to permit circularization. The model provides satisfactory explanations for observed genetic interactions (particularly recombination and heterozygote formation), for inactivation data and for selective subunit transcription.

The hydrodynamic permeability of normal term human amnion is measured using pressure-driven bulk flows. The permeability coefficient is found to vary widely, variations between tissues taken from different subjects being significantly greater than those from samples taken from one subject. No correlation is observed between this coefiicient and either tissue thickness or the diffusional permeability coefficient measured using tritiated water; it is, however, found to be very sensitive to epithelial damage. The results indicate that the bulk transport of water through amnion is largely controlled by the amniotic epithelium alone. This contrasts with water diffusion which is a function of total membrane thickness. The two permeability coefficients cannot therefore be employed to formulate an equivalent pore model of the whole tissue. An equivalent pore model of the epithelial layer only is considered and the results assessed in the light of other evidence bearing on the structure of amnion. It is concluded that the epithelial layer is intersected by a large number of pores with radius 10 to 30 A, and a smaller number of much broader pores.

The question of how many grams of an organism can grow heterotrophically from only 1·0 g of glucose and adequate minerals has been put forward many times. Only a few attempts have been made to answer this question theoretically and these attempts were rather rough. In this paper, it is demonstrated that the yield of a growth process may be accurately computed by considering the relevant biochemistry of conversion reactions and the cytological implications of biosynthesis and growth. Oxygen consumption and carbon dioxide production by these processes are also computed. The weight of the biomass synthesized from 1·0 g of substrate and the quantities of gases exchanged are independent of temperature. These results are obtained by adding the individual equations describing the formation of each compound synthesized by the organism from the substrate supplied. The sum represents an equation which accounts for all substrate molecules required for biosynthesis of the carbon skeletons of an end-product, whose chemical composition is given. It is then calculated how much energy is required for the non-synthetic processes which form a part of biosynthesis, such as intra- and intercellular transport of molecules and maintenance of RNA and enzymes. The additional amount of substrate required to provide this energy by combustion is easily calculated. Adding this substrate to the amount used for skeleton synthesis gives an overall equation which quantifies the substrate and oxygen demand as well as carbon dioxide evolution during biosynthesis of 1·0 g biomass. For example, it requires 1·34 g of glucose with adequate ammonia and minerals to synthesize 1·0 g maize plant biomass in darkness; during this process 0·14 g oxygen are consumed and 0·24 g carbon dioxide are produced. It has been described elsewhere that similar results were obtained experimentally with growing plants. Such results depend considerably upon the chemical composition of the biomass being synthesized and upon the state (oxidized or reduced) of the nitrogen source. Other parameters, such as the number of ATP molecules required for protein synthesis, the possibility for utilization of alternative pathways for synthesis or energy production, the presence or absence of compartmentation of synthetic processes and variations in the P/O ratio between two and three, under many conditions affect results of the computation less than 10%. Since maintenance of cellular structures is not considered, the approach concerns the gross yield of biosynthesis. It predicts therefore the dry matter yield of heterotrophic cells from a given quantity of substrate at high relative growth rates.

2 H NMR spectra have been observed for several selectively deuterated phospholipid and fatty acid probes intercalated in the liquid crystalline phase of egg phosphatidylcholine in aqueous dispersion. For unsonicated lamellar dispersions and planar multibilayers, quadrupole splittings may be observed which lead directly to a value for the order parameter for the carbon-deuterium bond. Sonicated dispersions yield high-resolution spectra, from which spin-lattice relaxation rates and correlation times for rotational diffusion can be obtained. The presence of cholesterol in the dispersion has no effect on the quadrupole splittings and relaxation rates for 2 H in the choline methyl groups, in contrast to its profound effect on the spectra for 2 H in the hydrocarbon chains.