Unusual Transformation of Mixed Isomer Decahydroisoquinoline Stable Glasses.

Dielectric relaxation was used to characterize the ability of vapor-deposited mixtures of cis- and trans-decahydroisoquinoline (DHIQ) to form glasses with a high kinetic stability. Vapor-deposited mixtures are technologically relevant, and the effect of mixing on glass stability is a relatively unexplored area. Mixed isomers and pure trans-DHIQ form highly stable glasses that isothermally transform in approximately 104 τα (where τα is the structural relaxation time of the supercooled liquid). Isomeric composition of the glasses does not play a significant role in the maximum kinetic stability of the resulting films. Secondary relaxations in DHIQ are associated with an intramolecular conformational change and are suppressed to a significant extent in highly stable glasses. During isothermal annealing experiments, stable glasses were found to transform initially via a growth front mechanism that transitions to a homogeneous bulk mechanism. Surprisingly, the time dependence of the bulk transformation is different from that reported for other stable glasses and cannot be interpreted in terms of a simple nucleation and growth model.

In situ observation of fast surface dynamics during the vapor-deposition of a stable organic glass.

By measuring the increments of dielectric capacitance (ΔC) and dissipation (Δtan δ) during physical vapor deposition of a 110 nm film of a molecular glass former, we provide direct evidence of the mobile surface layer that is made responsible for the extraordinary properties of vapor deposited glasses. Depositing at a rate of 0.1 nm s-1 onto a substrate at Tdep = 75 K = 0.82Tg, we observe a 2.5 nm thick surface layer with an average relaxation time of 0.1 s, while the glass growing underneath has a high kinetic stability. The level of Δtan δ continues to decrease for thousands of seconds after terminating the deposition process, indicating a slow aging-like increase in packing density near the surface. At very low deposition temperatures, 32 and 42 K, the surface layer thicknesses and mobilities are reduced, as are the kinetic stabilities.

Pattern formation in auxin flux.

The plant hormone auxin is fundamental for plant growth, and its spatial distribution in plant tissues is critical for plant morphogenesis. We consider a leading model of the polar auxin flux, and study in full detail the stability of the possible equilibrium configurations. We show that the critical states of the auxin transport process are composed of basic building blocks, which are isolated in a background of auxin depleted cells, and are not geometrically regular in general. The same model was considered recently through a continuous limit and a coupling to the von Karman equations, to model the interplay of biochemistry and mechanics during plant growth. Our conclusions might be of interest in this setting, since, for example, we establish the existence of Lyapunov functions for the auxin flux, proving in this way the convergence of pure transport processes toward the set of equilibrium points.

Steady-state expression of self-regulated genes.

MOTIVATION: Regulatory gene networks contain generic modules such as feedback loops that are essential for the regulation of many biological functions. The study of the stochastic mechanisms of gene regulation is instrumental for the understanding of how cells maintain their expression at levels commensurate with their biological role, as well as to engineer gene expression switches of appropriate behavior. The lack of precise knowledge on the steady-state distribution of gene expression requires the use of Gillespie algorithms and Monte-Carlo approximations. METHODOLOGY: In this study, we provide new exact formulas and efficient numerical algorithms for computing/modeling the steady-state of a class of self-regulated genes, and we use it to model/compute the stochastic expression of a gene of interest in an engineered network introduced in mammalian cells. The behavior of the genetic network is then analyzed experimentally in living cells. RESULTS: Stochastic models often reveal counter-intuitive experimental behaviors, and we find that this genetic architecture displays a unimodal behavior in mammalian cells, which was unexpected given its known bimodal response in unicellular organisms. We provide a molecular rationale for this behavior, and we implement it in the mathematical picture to explain the experimental results obtained from this network.

Mathematical analysis of competition between sensory ganglion cells for neurotrophic factor in the skin.

A model is presented of competition between sensory axons for trophic molecules (e.g. a neurotrophin such as NGF), produced in a region of skin small enough to permit their free diffusion throughout it; e.g., a touch dome, or a vibrissal follicle hair sinus. The variables specified are the number of high affinity trophic factor receptors per axon terminal and the concentration of trophic factor in the extracellular space. Previous models of this class predicted the loss of all the axons innervating the region except the one requiring least trophic factor for its maintenance, even with high rates of trophic factor production. In the present model, we have imposed upper limits to axonal growth, thereby introducing new equilibria, and we show by a global analysis using LaSalle's theorem, and also by local analysis, that several axons can then coexist if the rate of production of trophic molecules is sufficiently high.

Computer simulation of the motoneuron pool-muscle complex. I. Input system and motoneuron pool.

The aim of the present study was to simulate the input system and the motoneuron (MN) pool of the MN pool-muscle complex (MNPMC). Input fibers, which can originate from command centers in the central nervous system or from sensory organs, activate the MN pool. They generate sequences of action potentials, the frequency of which is proportional to a time-dependent activation factor (which is an input to the model). Different connection patterns between the input fibers and motor units (MUs) are allowed. For simplicity and since no precise experimental data are available, 70 input fibers and 4 boutons per fiber and MN are simulated (this corresponds approximately to the monosynaptic group-Ia input of the cat medial gastrocnemius muscle). Each bouton generates the same conductance change in the postsynaptic membrane. The MNs are modeled with a single compartment and a homogeneous membrane. According to experimental data, the membrane leakage conductance and capacitance are MU dependent. Since the precise relation is unknown: (a) the computed relation between MU contraction force and the MN leakage conductance was taken from a steady-state MNPMC model, and (b) the capacitance was assumed to be proportional to the leakage conductance. The MN membrane includes time- and voltage-dependent ionic channels (fast and slow K(+) and low- and high-threshold Ca(2+) channels). The density and time constant of the slow K(+) channels and the density of the Ca(2+) channels were fitted to approximate afterhyperpolarization characteristics and frequency-injected current relations of type-identified cat MNs. If the membrane reaches a voltage threshold the MNs generate action potentials, which were simulated by voltage pulses. The activation of the MN pool of the human first dorsal interosseus muscle was simulated with injected and synaptic currents in order to illustrate the size principle, synaptic noise, and other features of muscle activation. It is concluded that the present model reproduces the main properties of the input-output relations of different MN types within a muscle. Together with the simulation of the muscle force and the surface EMG, which will be published in subsequent papers, it will be a powerful tool for reproducing experiments on the motor system and investigating functional mechanisms of motor control.

Computed tomographic scanning of cervical spine fractures: does it influence treatment?

OBJECTIVE: To determine whether the superior sensitivity of computed tomography (CT) results in changes in treatment plans for cervical spine fractures that have been diagnosed on plain films alone. DESIGN: Retrospective review of radiographic studies for cervical spine trauma. SETTING/PARTICIPANTS: An orthopaedic spine surgeon (SS), an orthopaedic traumatologist (OT), an orthopaedic spine fellow (SF), and an orthopaedic chief resident (CR) were independently presented thirty-nine cases of cervical spine trauma imaged with adequate plain radiographs and with CT. MAIN OUTCOME MEASURES: Agreement was measured by calculation of kappa coefficients. RESULTS: The detection rate of total fractures on plain radiographs alone ranged from 47 percent to 71 percent, and the diagnosis changed an average 53 percent of cases. Change in treatment plans ranged from 10 percent (SS) to 46 percent (CR) of cases. Of these changes, undertreatment occurred as follows: SS =3 percent, OT =8 percent, SF =36 percent, and CR = 46 percent. The mean kappa coefficient for intraobserver agreement of treatment plans was 0.69. The experienced observers demonstrated "excellent" agreement with an average kappa coefficient of 0.85, whereas the mean coefficient for inexperienced observers was 0.54 or "moderate" agreement. Complete diagnostic agreement occurred between the experienced observers after review of both the plain films and CT scans. The interobserver agreement of treatment plans for the experienced observers increased from 0.79 to 0.88. CONCLUSIONS: CT scanning afforded additional information for all observers. Experienced observers can reliably determine treatment plans for cervical spine trauma diagnosed on plain films alone, whereas inexperienced observers are less reliable. For the experienced observers, interobserver agreement on treatment plans increased after the addition of CT.

A model for steady isometric muscle activation.

The present model of the motoneuronal (MN) pool-muscle complex (MNPMC) is deterministic and designed for steady isometric muscle activation. Time-dependent quantities are treated as time-averages. The character of the model is continuous in the sense that the motor unit (MU) population is described by a continuous density function. In contrast to most already published models, the wiring (synaptic weight) between the input fibers to the MNPMC and the MNs (about which no detailed data are known) is deduced, whereas the input-force relation is given. As suggested by experimental data, this relation is assumed to be linear during MU recruitment, but the model allows other, nonlinear relations. The input to the MN pool is defined as the number of action potentials per second in all input fibers, and the excitatory postsynaptic potential (EPSP) conductance in MNs evoked by the input is assumed to be proportional to the input. A single compartment model with a homogeneous membrane is used for a MN. The MNs start firing after passing a constant voltage threshold. The synaptic current-frequency relation is described by a linear function and the frequency-force transformation of a MU by an exponential function. The sum of the MU contraction forces is the muscle force, and the activation of the MUs obeys the size principle. The model parameters were determined a priori, i.e., the model was not used for their estimation. The analysis of the model reveals special features of the activation curve which we define as the relation between the input normalized by the threshold input of the MN pool and the force normalized by the maximal muscle force. This curve for any muscle turned out to be completely determined by the activation factor, the slope of the linear part of the activation curve (during MU recruitment). This factor determines quantitatively the relation between MU recruitment and rate modulation. This property of the model (the only known model with this property) allows a quantification of the recruitment gain (Kernell and Hultborn 1990). The interest of the activation factor is illustrated using two human muscles, namely the first dorsal interosseus muscle, a small muscle with a relatively small force at the end of recruitment, and the medial gastrocnemius muscle, a strong muscle with a relatively large force at the end of recruitment. It is concluded that the present model allows us to reproduce the main features of muscle activation in the steady state. Its analytical character facilitates a deeper understanding of these features.

A comparative evaluation of halo pin designs in an immature skull model.

To design an improved halo pin for use in pediatric patients, three commonly used halo pins were evaluated with a mechanical testing apparatus and segments of prepared fetal calf skull. The pins were driven through the bone segments while the load at the bone-pin interface was measured. New pins were designed with respect to pin tip and flange width and similarly compared. Mean maximum loads to penetration, normalized for bone segment thickness, were 55.6 N/mm for the PMT Corporation pin, 61.5 N/mm for the Bremer pin, and 73.6 N/mm for the Ace pin. Four new, short tipped pins were designed and compared with the Ace pin, and there was no significant difference. Finally, four new pins were designed with varying flange widths. Mean maximum loads, normalized for bone segment thickness, were 68.9 N/mm for the 4.2 mm flange, 72.2 N/mm for the 4.7 mm flange, 92.9 N/mm for the 5.2 mm flange, and 96.4 N/mm for the 5.7 mm flange. The findings of this investigation are clinically important because they may help to explain the variability in the complication rates seen with the use of different halo systems in children. The three halo pins currently on the market have different pin designs, including tip lengths and flange distances, which contribute to the difference in load to penetration for each pin. The new, wide flanged, short tipped halo pin design might decrease the complication rate of halo use in children by providing an improved capacity to resist penetration despite increased loads of application.

Inhibitory Effect of Organic Acids upon Meat Spoilage Bacteria.

The relative ability of acetic, benzoic, citric, lactic, propionic, and sorbic acids to inhibit the growth of six common meat spoilage bacteria ( Brochothrix thermosphacta , Carnobacterium piscicola , Lactobacillus curvatus , Lactobacillus sake , Pseudomonas fiuorescens , and Serratia liquefaciens ) was compared under otherwise optimum conditions (BHI or MRS broths; 20°C). Because of their low solubility in the growth media, benzoic and sorbic acids could only be used in low concentrations (below 0.15% [wt/vol]) and did not efficiently inhibit bacterial growth. All other acids totally inhibited growth at concentrations ranging from 0.1 % to 1% (wt/vol). On a weight basis, acetic acid was found to be the most inhibitory, followed by propionic. lactic, and citric acid, while the order of efficiency was reversed (citric> lactic> propionic> acetic) when the acid concentrations were expressed on a molar basis or when the acid effectiveness was evaluated relative to the concentration of undissociated molecules. Overall, the lactobacilli were the bacteria most resistant to the action of organic acids, followed by P. fiuorescens and S. liquefaciens , while B. thermosphacta and C. piscicola were considerably more sensitive.

Competitive exclusion between axons dependent on a single trophic substance: a mathematical analysis.

A mathematical model is presented of competition between axons for a trophic substance, such as is believed to occur particularly during development. The model is biologically realistic. The growth-stimulating activity of the trophic molecules is assumed to result from their binding to high-affinity receptors on neurons and their axons, but the model also incorporates uptake by nonneuronal cells possessing only lower affinity receptors. Plausible and fairly general assumptions are made concerning the kinetics of binding and internalization and the effects on axonal growth. The model takes into account the possibility that trophic factor production may be regulated by the afferent axons or autoregulated. The variables specified are the "axonal vigor" of each axon, representing the ability of each axon to take up trophic molecules, and the concentration of trophic molecules in the extracellular space of the axonal target region. Of the several parameters introduced, the most important turns out to be the "zero vigor-growth parameter," which is defined as the concentration of trophic molecules that gives zero growth of the vigor of a given axon. By means of a Lyapunov function, it is shown that the system will approach asymptotically to a stable equilibrium characterized by the survival of only the axon whose zero-growth parameter is lowest. Or, if several axons share the same lowest zero-growth parameter, these will all survive. The model may be particularly relevant to the elimination of polyneuronal innervation from developing muscle fibers and from autonomic ganglion cells.

Urea kinetic modeling: an in vitro and in vivo comparative study.

The urea kinetic model (UK) and the direct dialysis quantification method based on dialysate collection (DDQ) were used to determine the urea distribution volume (V) identified with the total body water and the urea generation rate (G) for different dialysis times, both in vivo during short hemodialysis (N = 20) and in vitro using an experimental single-pool urea system (N = 10). Both UK and DDQ allowed a satisfactory in vitro estimation of V and G for all dialysis times. On the other hand in vivo V and G estimations by both methods showed an increase of more than 50% between the determinations performed after 30 minutes of dialysis and at the end of dialysis. Our theoretical analysis shows that the in vivo changes of V are compatible with those expected for a two-compartment system in which one compartment is cleared faster than the other. Furthermore, given that urea is allowed to equilibrate in the body at the end of dialysis, DDQ permits an accurate estimate of V, G and PCR even for short hemodialysis, which UK does not.

[A flow divider which permits, during hemodialysis, the continuous collection of a representative sample of dialysate]. / Un diviseur de flux qui permet, en cours d'hémodialyse, le recueil continu d'un échantillon représentatif du dialysat.

Dialysis efficiency is evaluated by the measurement of transfer of urea as well as of other important solutes such as sodium, potassium, phosphates etc. from the blood to the dialysate. These determinations are usually made by using clearances, but, because of the internal dynamics in the blood itself, reliable measurements taken in this way are impossible for most of the solutes of interest. Our system avoids these difficulties and provides accurate results. A reference method requires the determination of the volume and the concentration of the effluent dialysate. This is used in research work, but for obvious reasons, it is not suitable to a daily clinical context. Several authors proposed a system based on a pump, in order to sample continuously a fraction of the dialysate. However, they have to assume a constant flow of the latter. The system described here has the advantage of collecting a representative sample of the whole dialysate regardless of flow and concentrations variations during dialysis. It is suitable to a clinical context, easy to use and silent.

Eradication of helminthic infections.

The eradication of helminthic infections described by models of the Nåsell-Hirsch type is investigated. Simple criteria are proposed for comparing the efficiency of different modes of eradication.

The effect of early versus late return to vigorous activities on the outcome of anterior cruciate ligament reconstruction.

The effect of early (mean, 5 months) versus late (mean, 9 months) return to vigorous cutting activity on the long-term outcome of anterior cruciate ligament reconstruction was evaluated retrospectively. Sixty-four reconstructions, using a distally attached medial one-third patellar tendon, were reviewed on an average of 46 months postoperatively. After surgery, the timing of return to vigorous activity was based on biologic fixation of the graft, a negative Lachman test, absence of effusion, and the patient's desire to return to previous activity. The 64 patients were retrospectively separated into two groups. The early group consisted of 31 patients who returned to activity 2 to 6 months after reconstruction, and the late group consisted of 33 patients who returned to activity 7 to 14 months after reconstruction. By clinical examination, KT-1000 arthrometer measurements, subjective evaluation, and Cybex testing, there were no differences between the early and late return groups except for reestablishment of final range of motion. At an average followup of 46 months, this study indicates that an early return to vigorous physical cutting activities after ACL reconstruction does not predispose patients to reinjury or a less satisfactory longterm result.

The normal glenohumeral relationships. An anatomical study of one hundred and forty shoulders.

We measured the dimensions of the humeral and glenoid articular surfaces in 140 shoulders that were representative of a given population of patients, and also evaluated several glenohumeral relationships. Ninety-six measurements were made in the shoulders of cadavera and forty-four, on magnetic resonance-imaging studies of living patients. Eighty-five per cent of the humeral measurements fell within eight fixed combinations of the radius of curvature and the thickness of the humeral head, in two-millimeter increments. The average radius of curvature of the humeral head in the coronal plane was 24 +/- 2.1 millimeters (range, nineteen to twenty-eight millimeters). The average thickness of the humeral head was 19 +/- 2.4 millimeters (range, fifteen to twenty-four millimeters). There was a wide variability in the size of the humeral head and a direct correlation between the differences in size and the heights in both men and women. The humeral articular surface was spherical in the center; however, the peripheral radius was two millimeters less in the axial plane than in the coronal plane. Thus, the peripheral contour of the articular surface was elliptical (ratio, 0.92). The radius of curvature of the glenoid, measured in the coronal plane, was an average of 2.3 +/- 0.2 millimeters greater than that of the humeral head. The average dimensions of the glenoid in the superior-inferior and anterior-posterior (lower half) directions were 39 +/- 3.5 millimeters (range, thirty to forty-eight millimeters) and 29 +/- 3.2 millimeters (range, twenty-one to thirty-five millimeters). The anterior-posterior dimension of the glenoid was pear-shaped, the lower half being larger than the top half. The ratio of the lower half to the top half was 1:0.80 +/- 0.01. There was a strong linear correlation between the lateral humeral offset and the size of the humeral head (radius of curvature and thickness). The average lateral humeral offset was 56 +/- 5.7 millimeters (range, forty-three to sixty-seven millimeters). The superior most point on the humeral articular surface was an average of 8 +/- 3.2 millimeters (range, three to twenty millimeters) cephalad to the top of the greater tuberosity. Our data show that reconstruction of the lateral humeral offset is important in optimization of the moment arm of the deltoid and rotator cuff and of the normal tension of the soft tissue after prosthetic reconstruction.

[A comparative approach to models of urea kinetics in hemodialysis treatment]. / Une approche comparative des modèles de la cinétique de l'urée dans le traitement par hémodialyse.

The importance of mathematical modeling in dialysis arose recently as a consequence of the achievement of individualized treatment therapies. Two distinct models were used in our center, namely the urea kinetic model (UK) and the direct dialysis quantification (ddq), for the estimation of the urea distribution volume (V) and the urea generation rate (G). It turned out that, for the same patient, they provided us with different results. The basic hypotheses on which the two models rely are poorly described in the literature. The aim of this paper is an attempt to fill this gap and to show that the discrepancy observed between the two models is not surprising at all. The study also shows that from a theoretical viewpoint, ddq is more appropriate than UK for the estimation of V and G. The question of the intrinsic quality of ddq is not discussed here.