Geothermal evidence from Canada for a cold period before recent climatic warming.

Three deep boreholes in a small area in Quebec, each having two high-accuracy temperature logs separated by 22 years, allow reliable determination of the ground surface temperature history during the past few centuries. The temperature logs show that the recent climatic warming was preceded by a cold period near the end of the 19th century in this area. The presence of such a cold period is also suggested by borehole temperature data from other areas in Canada.

5'-nucleotidase activity in prostatic carcinoma and benign prostatic hyperplasia.

In light of previous reports of alterations in 5'-nucleotidase activity in neoplastic conditions, 5'-nucleotidase activity was examined histochemically in tissue sections and quantified biochemically in extracts of human hyperplastic prostates and prostatic carcinomas obtained surgically. The 5'-nucleotidase activities per mg protein in extracts of 29 prostatic carcinomas were lower (P less than 0.0005) than in extracts from 10 samples of benign prostatic hyperplasia. The 5'-nucleotidase activity per mg protein in extracts of prostatic carcinoma from the 29 patients correlated (R = -0.369, P = 0.049) with the degree of histological differentiation; the extracts of poorly differentiated carcinomas contained low levels of 5'-nucleotidase. When age and histological differentiation (Gleason's grade) were adjusted, the enzyme activity per mg protein correlated (R = 0.242, P = 0.004) with patient survival. When all three parameters were considered together, i.e., histological grade of the tumor, 5'-nucleotidase extracted from the tumor, and age of the patient, they were found to be mutually complementary for the prediction of patient survival (R = 0.388, P = 0.0001). To our knowledge, this is the first report that prostatic epithelium expresses 5'-nucleotidase; further work will be required to define the reasons for the high levels of activity observed in prostates without cancer and for the decrease in the activity in prostatic carcinoma.

Minimum instructional and program-specific administrative costs of educating residents in internal medicine.

BACKGROUND: The cost associated with education of residents is of interest from an educational as well as a political perspective. Most studies report a single institution's actual incurred costs, based on traditional cost accounting methods. We quantified the minimum instructional and program-specific administrative costs for residency training in internal medicine. METHODS: Using the Accreditation Council for Graduate Medical Education program requirements for internal medicine as minimum standards for teaching and administrative effort, we quantified the minimum instructional and administrative costs for sponsorship of an accredited residency program in internal medicine. We also analyzed the impact of resident complement and program curricular emphasis (outpatient, inpatient, or traditional) on the per-resident cost. The main outcome measure was the minimum annual per-resident cost of instruction and program-specific administration. RESULTS: Using the assumptions in this model, we estimated the annual cost per resident of implementing the program requirements to be $50,648, $35,477, $28,517, and $26,197 for inpatient intensive residency programs with resident complements of 21, 42, 84, and 126, respectively. For outpatient intensive residency programs of identical resident complements, we estimated the annual per-resident cost to be $58,025, $42,853, $35,894, and $33,574 for similar resident complements. Fixed costs mandated by the program requirements, which did not vary across program size or configuration, were estimated to be $640,737. CONCLUSIONS: There are fixed and variable costs associated with sponsorship of accredited internal medicine residency programs. The minimum cost per resident of education and departmental administration varies inversely with program size within the sizes examined.

Electrochemical characteristics of platinum electrodes coated with cytochrome b5-phospholipid monolayers.

Platinum electrodes can be coated with cytochrome b5-phospholipid monolayers by the Langmuir-Blodgett technique. Cyclic voltammetry of a series of dyes shows that the coated electrodes become selective for certain electroactive species. The electron transfer reactions of negatively charged species are inhibited at the modified electrode, whereas positively charged species show enhanced reactivity compared with that at a bare metal electrode.

Electronic processes in biology. The seventeenth Douglas Lea Lecture.

The growing similarities between modern microelectronic circuits and living systems increasingly suggest the electronic nature of the latter. Indeed, the ideas of quantum-mechanical electron tunneling or hopping between localised states developed in physics to explain conduction in non-crystalline solids are readily applicable to biology. Electron tunnelling transitions between energy states localised in biomolecules can explain such vital processes as photosynthesis, respiration and visual reception, and also form a logical framework to explain reactions induced by high energy radiolysis. It is suggested that there is sufficient evidence to support an argument that the same quantum-mechanical tunnelling process will occur through the localised states set up in biopolymers such as the proteins. The consequence would be highly vectorial electron transport along biopolymer pathways, the results of which are shown to have far-reaching implications. There is considerable difficulty in verifying these ideas experimentally and progress has been slow, but it is very probable that electronic physics is now poised to provide a framework for a new understanding of biology.

The effect of solvation on the ultrasonic absorption of bovine serum albumin solutions.

The role of solvation and structural equilibria in determining the ultrasonic absorption of aqueous solutions of bovine serum albumin has been investigated using chemical agents to denature the protein in solution. The agents used were methanol, ammonium sulphate, and guanidine hydrochloride. Two different techniques of measurement were used to cover the frequency range 200 kHz to 30 MHz. The results show that only guanidine hydrochloride produces a significant change in ultrasonic absorption even though the other agents were used at concentrations close to those which would produce protein precipitation. The conclusion is that in the above frequency range structural and solvation-related equilibria are unimportant and only perturbation of proton-transfer equilibria associated with the protein amino acid residues leads to the bulk of the ultrasonic absorption.

Community participation in the certificate-of-need process: a look at ten-taxpayer groups in Massachusetts.

Certificate-of-need statutes give designated state agencies veto power over investment in health care facilities. Some states have sought to temper the arbitrary character of this power by expanding the opportunities for community input into the certificate-of-need process. Massachusetts, for example, has enacted a statute that allows groups of ten taxpayers to petition for a public hearing on any certificate-of-need application. Some observers question whether the benefits of taxpayer-group participation are substantial enough to compensate for the delays and abuses that the statute allegedly invites. To help resolve this question, this Comment examines historical data on Massachusetts taxpayer groups and on their activities and assesses the significance of their composition and tactics to the certificate-of-need process. Although flaws exist in the Massachusetts ten-taxpayer mechanism, in this writer's view it has succeeded partially in making the certificate-of-need process responsive to community opinion. Many groups lack the skills and qualities needed to make constructive use of the ten-taxpayer mechanism. Nevertheless, it serves a valuable purpose by creating a public forum for and by encouraging public participation in the certificate-of-need process, especially by those who might otherwise try to circumvent that process through use of special legislation, of private pressure, or of other similar means.

The mechanisms of conduction in proteins.

Theoretical calculations have already shown that the electronic properties of biopolymers may be described in terms of conduction and valence energy bands in which electrons are delocalized to a significant degree. Because these bands are separated by a large energy gap, it is concluded that electronic conduction in such systems must be by 'holes' in the valence band. The mechanism of this conduction is discussed with special reference to dry proteins where the charge-transfer role of appropriate acceptor molecules and the modulating influence of amino acid residues will encourage localized and delocalized hole production at the valence band edge. It is suggested that there are close similarities, which have shown up in measurements, in the electrical behaviour of proteins and other non-biological semi-crystalline solids. The significance of such long-range conduction and attendant polarization is considered briefly in the light of evidence for the existence of proteins in cell membranes and in the skeleton of the cytoplasm

Integrating handheld PCs into a PACS network with commercially available components.

A palm computer with a 160 x 160-pixel display and 16-bit color depth can display useable images if the viewing software supports a larger image file size and zooming functions. Flash memory modules are now available. Storage of large image files is no longer a problem.

Self-organized synchronous oscillations in a network of excitable cells coupled by gap junctions.

Recent evidence suggests that electrical coupling plays a role in generating oscillatory behaviour in networks of neurons; however, the underlying mechanisms have not been identified. Using a cellular automata model proposed by Traub et al (Traub R D, Schmitz D, Jefferys J G and Draguhn A 1999 High-frequency population oscillations are predicted to occur in hippocampal pyramidal neural networks interconnected by axo-axonal gap junctions Neuroscience 92 407-26), we describe a novel mechanism for self-organized oscillations in networks that have strong, sparse random electrical coupling via gap junctions. The network activity is generated by random spontaneous activity that is moulded into regular population oscillations by the propagation of activity through the network. We explain how this activity gives rise to particular dependences of mean oscillation frequency on network connectivity parameters and on the rate of spontaneous activity, and we derive analytical expressions to approximate the mean frequency and variance of the oscillations. In doing so, we provide insight into possible mechanisms for frequency control and modulation in networks of neurons.

Chaotic dynamics in an ionic model of the propagated cardiac action potential.

We simulate the effect of periodic stimulation on a strand of ventricular muscle by numerically integrating the one-dimensional cable equation using the Beeler-Reuter model to represent the transmembrane currents. As stimulation frequency is increased, the rhythms of synchronization [1:1----2:2----2:1----4:2---- irregular----3:1----6:2----irregular----4:1----8:2----...----1:0] are successively encountered. We show that this sequence of rhythms can be accounted for by considering the response of the strand to premature stimulation. This involves deriving a one-dimensional finite-difference equation or "map" from the response to premature stimulation, and then iterating this map to predict the response to periodic stimulation. There is good quantitative agreement between the results of iteration of the map and the results of the numerical integration of the cable equation. Calculation of the Lyapunov exponent of the map yields a positive value, indicating sensitive dependence on initial conditions ("chaos"), at stimulation frequencies where irregular rhythms are seen in the corresponding numerical cable simulations. The chaotic dynamics occurs via a previously undescribed route, following two period-doubling bifurcations. Bistability (the presence of two different synchronization rhythms at a fixed stimulation frequency) is present both in the simulations and the map. Thus, we have been able to directly reduce consideration of the dynamics of a partial differential equation (which is of infinite dimension) to that of a one-dimensional map, incidentally demonstrating that concepts from the field of non-linear dynamics--such as period-doubling bifurcations, bistability, and chaotic dynamics--can account for the phenomena seen in numerical simulations of the cable equation. Finally, we sketch out how the one-dimensional description can be extended, and point out some implications of our work for the generation of malignant ventricular arrhythmias.

Shear-wave detection of structural effects in aqueous solutions of bovine serum albumin and hemoglobin.

Using cylindrical quartz crystal torsional resonators operating at 39 and 75 kHz to generate shear waves in aqueous solutions of the proteins bovine serum albumin and hemoglobin and the polypeptide poly l-glutamic acid, it has been possible to determine the complex dynamic shear viscosities of the solutions. The effects of concentration, pH, and denaturation using various agents have been studied. It is possible to relate the viscosity and configurational elasticity of the solutions, to the intramolecular and intermolecular forces associated with the of the proteins at frequencies between 60 and 400 kHz and attributed to conformational changes of bovine serum albumin and the quaternary doublet interactions of hemoglobin have been confirmed and emphasized by the use of shear waves.

The biphasic mystery: why a biphasic shock is more effective than a monophasic shock for defibrillation.

We demonstrate that a biphasic shock is more effective than a monophasic shock at eliminating reentrant electrical activity in an ionic model of cardiac ventricular electrical activity. This effectiveness results from early hyperpolarization that enhances the recovery of sodium inactivation, thereby enabling earlier activation of recovering cells. The effect can be seen easily in a model of a single cell and also in a cable model with a ring of excitable cells. Finally, we demonstrate the phenomenon in a two-dimensional model of cardiac tissue.

Ultrasonic absorption of bovine serum albumin solutions in the frequency range 60 to 160 kHz.

The ultrasonic absorption of the globular protein bovine serum albumin in aqueous solution has been measured in the frequency range 60 to 160 kHz using a 2-1 spherical resonator. The effect of pH change and of the denaturants urea, guanidine hydrochloride, and sodium dodecyl sulfate on the absorption loss has been studied. It is concluded that a significant ultrasonic absorption process exists which is related to structural helix-coil transition equilibria. For native protein the maximum loss appears to occur at a frequency at least as low as 70 kHz for a pH of about 4.2. This loss process is distinct from those arising from proton-transfer equilibria perturbations which are manifest at pH 3.2 and 11.6 and at peak frequencies of 400 kHz and above.

Low-frequency ultrasound absorption in aqueous solutions of hemoglobin, myoglobin, and bovine serum albumin: the role of structure and pH.

New measurements on ultrasound absorption of aqueous solutions of the three globular proteins, bovine hemoglobin, horse heart myoglobin, and bovine serum albumin, at 20 degrees C are reported for the frequency range below 1.2 MHz and, in the case of hemoglobin and bovine serum albumin, to a limited extent for the range 2-30 MHz. The effect of protein conformation has been investigated by use of a range of denaturants and by change of pH. A much more detailed description of protein interactions emerges from the low-frequency studies than was possible hitherto. Specific absorption processes for myoglobin and bovine serum albumin peak in the neighborhood of pH 4.2. The process for myoglobin has a relaxation frequency between 1 and 2.6 MHz, while for bovine serum albumin the frequency is as low as 70 kHz. Both processes can be related to conformational changes in the molecules. In the case of hemoglobin, an absorption process with a relaxation frequency of 600 kHz is found that can be attributed to the dissociation equilibrium of the quaternary structure of the molecule and can be considerably enhanced by denaturants or pH change from neutral to acid conditions. Measurements at frequencies down to 200 kHz have also permitted a more thorough investigation of proton-transfer reactions at carboxyl and amino groups in these proteins and of the effect of pH on these reactions.

Ultrasonic absorption of bovine serum albumin solutions in the frequency range 200 kHz-1 MHz.

The ultrasonic absorption of solutions of two electrolytes, magnesium and manganous sulfates, and also of the globular protein bovine serum albumin, has been measured using small volume spherical resonators at frequencies in the range 200 kHz-1.2 MHz. The principles of the technique are discussed and absorption values obtained for the electrolyte solutions at 20 degrees C are compared with existing values using other methods. For BSA, measurements were made at 8 degrees C over a range of pH values. Under both acid and alkaline conditions, excess losses at megahertz frequencies were found to persist down to at least 200 kHz. A new loss peak at approximately 400 kHz has been found at pH 3.2.

Pre-steady-state analysis of ATP hydrolysis by Saccharomyces cerevisiae DNA topoisomerase II. 2. Kinetic mechanism for the sequential hydrolysis of two ATP.

In the preceding paper, we showed that DNA topoisomerase II from Saccharomyces cerevisiae binds two ATP and rapidly hydrolyzes at least one of them before encountering a slow step in the reaction mechanism. These data are potentially consistent with two different types of reaction pathways: (1) sequential ATP hydrolysis or (2) simultaneous hydrolysis of both ATP. Here, we present results that are consistent only with topoisomerase II hydrolyzing its two bound ATP sequentially. Additionally, these results indicate that the products of the first hydrolysis are released from the enzyme before the second ATP is hydrolyzed. Release of products from both the first and second hydrolyses contributes to the rate-determining process. The proposed mechanism for ATP hydrolysis by topoisomerase II is complex, having nine rate constants. To calculate values for each of these rate constants, a technique of kinetic parameter estimation was developed. This technique involved using singular perturbation theory in order to estimate rate constants, and consequently identify kinetic steps following the rate-determining step.

Spatial self-organisation in ecology: pretty patterns or robust reality?

Many seemingly plausible mathematical models of small-scale ecological interactions predict the self-organisation of dynamic, coherent and large scale spatial patterns (e.g. spirals). If true, such patterns would have important ecological and evolutionary consequences. For the most part, however, empirical studies have not corroborated their existence, suggesting erroneous dynamics in the models, shortcomings in empirical methodology, or both. Arguments for categorically dismissing self-organized patterns have been based on their assumed sensitivity to symmetry-breaking stochastic noise. However, many plausible mechanisms for generating patterns are robust to noise, and consequently broken symmetry is insufficient grounds for dismissing these self-organized patterns.