SEARCH · Search PubMed

Results for “Equilibrium optimization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,675 records · Page 93Linked to original sources

PubMed2000

Coordination of two- and one-joint muscles: functional consequences and implications for motor control.

The purpose of this paper is three-fold: (a) to summarize available data on coordination of major two- and one-joint muscles in multijoint tasks and identify basic features of muscle coordination, (b) to demonstrate that there may exist an optimization criterion that predicts essential features of electromyographic activity of individual muscles in a variety of tasks, and (c) to address the functional consequences of the observed muscle coordination and underlying mechanisms of its control. The analysis of the literature revealed that basic features of muscle coordination are similar among different voluntary motor tasks and reflex responses. It is demonstrated that these basic features of coordination of one- and two-joint muscles in two-dimensional tasks are qualitatively predicted by minimizing the sum of muscle stresses cubed. Functional consequences of the observed coordination of one- and two-joint muscles are (a) reduction of muscle force as well as stress, mechanical and metabolic energy expenditure, muscle fatigue, and perceived effort; (b) a spring-like behavior of a multi-joint limb during maintenance of an equilibrium posture; and (c) energy transfer between joints via two-joint muscles. A conceptual scheme of connections between motoneuron pools of one- and two-joint muscles, which accounts for the observed muscle coordination, is proposed. An important part of this scheme is the force-dependent inhibition and excitation from two-joint to one-joint synergists and antagonists, respectively.

Electromyography↗

PubMed1986

High chronic ambient temperature stress effects on broiler acid-base balance and their response to supplemental ammonium chloride, potassium chloride, and potassium carbonate.

Four experiments were conducted to evaluate the effect of heat stress on acid-base status and the birds' response to supplemental KCl and KCO3. The corn-soybean meal fish-meal basal ration (.73% K+) contained more K+ and Cl- than is recommended by the National Academy of Sciences for chicks reared under near optimal conditions (24 C and 55% relative humidity). Chicks reared under continuous thermostress (35 C, 70% relative humidity) exhibited panting phase blood alkalosis (pH of 7.46). Supplementing drinking water with .2% NH4Cl reduced panting phase blood pH to normal values and increased live weight gain (23%) and feed efficiency (7.7%). Supplementing drinking water with .15% KCl also increased (P less than .05) live weight gain (46%) and feed efficiency (15.4%) but did not affect (P less than .46) blood pH. A significant (P less than .01) interaction existed between NH4Cl and KCl for body weight gain. Adding .2% NH4Cl to broiler drinking water reduced the level of KCl required in drinking water to optimize weight gain to .1% KCl. Potassium chloride alone, or with NH4Cl, can alleviate some consequences of heat stress, but supplementing drinking water with a high level of NH4Cl (.5%) decreased (P less than .05) blood pH to acidotic levels and reduced body weight gain. Potassium chloride supplementation exacerbated NH4Cl toxicity. Potassium carbonate reduced (P less than .05) body weight gain indicating that the response may not be attributed to K+ alone. Beneficial effects of NH4Cl therapy for heat stressed broilers are speculative.

Acid-Base Equilibrium↗

PubMedDate not supplied

Application of a fed-batch system to produce RNA by in vitro transcription.

A novel fed-batch method is presented for the production of RNA by in vitro transcription performed in a stirred-cell reactor with pH-controlled addition of reaction components. Solution equilibrium analysis is applied to determine the ratios of feed components (including nucleoside triphosphates (NTPs), magnesium salt, and base) which allow the desired NTP concentrations, free magnesium concentration, and pH to be maintained during the reaction. Results are presented for fed-batch and batch reactions performed with two DNA templates encoding a 12mer RNA and a 38mer RNA. For the dodecamer RNA, the fed-batch mode is only modestly better than batch reactions, with no significant increase in the efficiency of NTP incorporation but with 40% improvement in the amount of RNA produced per unit of polymerase or DNA. For the 38mer, fed-batch transcription provides a substantial increase in the efficiency of NTP incorporation and 100% improvement in the production of RNA per unit of polymerase or DNA. Cost analyses are presented which show how optimal NTP concentrations in batch and fed-batch reactions will be dependent on the relative costs of NTPs, T7 RNA polymerase, and DNA templates for the particular application. The use of a fed-batch mode appears to have the potential for substantial improvement in the economics of RNA production for at least some RNA sequences.

Acid Anhydride Hydrolases↗

PubMed2000

Thermodynamic molecular switch in macromolecular interactions.

It is known that most living systems can live and operate optimally only at a sharply defined temperature, or over a limited temperature range, at best, which implies that many basic biochemical interactions exhibit a well-defined Gibbs free energy minimum as a function of temperature. The Gibbs free energy change, deltaG(o) (T), for biological systems shows a complicated behavior, in which deltaG(o)(T) changes from positive to negative, then reaches a negative value of maximum magnitude (favorable), and finally becomes positive as temperature increases. The critical factor in this complicated thermodynamic behavior is a temperature-dependent heat capacity change (deltaCp(o)(T) of reaction, which is positive at low temperature, but switches to a negative value at a temperature well below the ambient range. Thus, the thermodynamic molecular switch determines the behavior patterns of the Gibbs free energy change, and hence a change in the equilibrium constant, Keq, and/or spontaneity. The subsequent, mathematically predictable changes in deltaH(o)(T), deltaS(o)(T), deltaW(o)(T), and deltaG(o)(T) give rise to the classically observed behavior patterns in biological reactivity, as demonstrated in three interacting protein systems: the acid dimerization reaction of alpha-chymotrypsin at low pH, interaction of chromogranin A with the intraluminal loop peptide of the inositol 1,4,5-triphosphate receptor at pH 5.5, and the binding of L-arabinose and D-galactose to the L-arabinose binding protein of Escherichia coli. In cases of protein unfolding of four mutants of phage T4 lysozyme, no thermodynamic molecular switch is observed.

Arabinose↗

PubMed1980

Oxacillin for bacterial endophthalmitis: subconjunctival, intravenous, both, or neither?

We compared the intraocular concentrations of oxacillin given by continuous intravenous infusion, subconjunctival injection, or combined therapy in a rabbit model of Staphylococcus aureus endophthalmitis. At equilibrium during intravenous infusion, concentrations in the aqueous humor, cornea, and choroid-retina were 25% to 30% of the serum level; in contrast, vitreous levels were only 2% of the serum concentration. Subconjunctival injection produced extremely high levels in the cornea and aqueous and moderate concentrations in the choroid-retina; vitreous penetration remained poor (<1 microgram/ml). Combined therapy offered little advantage in terms of concentrations in the aqueous or cornea and had a modest effect on levels in the choroid-retina. Vitreous concentrations showed a striking relation to serum levels with all regimens, including subconjunctival ones; although this could have been fortuitous, it suggests an important role for the hematogenous route in this model. Only those modes of delivery producing serum concentrations greater than 50 micrograms/ml consistently resulted in vitreous levels greater than 0.4 microgram/ml. The optimal therapy of bacterial endophthalmitis may require direct intravitreal injection of antibiotic.

Animals↗

PubMed1987

Changes of synaptosomal energy metabolism induced by hypoxia during aging.

Synaptosomes were isolated from the motor area of the cerebral cortex of normoxic or hypoxic (PaO2 = 17-19 mmHg, for 15 min) beagle dogs of different ages. Synaptosomes were incubated in Krebs-Henseleit-Hepes buffer (for 10 min at 24 degrees C) and the energetic state was defined by: the balance of the labile phosphates (ATP, ADP, AMP, and creatine phosphate); the respiratory rate; the redox state of the intramitochondrial NAD-couple. By the present experimental model, it is possible to evaluate the potential damage (induced by the "in vivo" hypoxic insult) that synaptosomes cannot reverse under optimal incubation. Aging affected the phosphorylation state of the post-hypoxic incubated synaptosomes. The oxygen consumption rate was quite similar in the synaptosomal fractions from the motor area of hypoxic beagle dogs of different ages, but the cytochrome c and a contents were lower in the preparations from hypoxic older brains. In dogs of different ages, hypoxia always lowered the respiration of the synaptosomes, but aging affected the oxygen consumption rates only in post-hypoxic synaptosomes incubated with succinate. The synaptosomal energetic state was defined also by the redox state of the intramitochondrial NAD-couple (delta Gox-red) and the phosphorylation state of adenine nucleotide system (delta GATP). The free-energy change (delta delta G) for the coupled reactions was calculated, too. In synaptosomes isolated from the cerebral cortex of dogs submitted to hypoxia, the equilibrium (calculated for the mitochondrial electron transfer chain and the phosphorylation of adenine nucleotides) was markedly altered as function of aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

PubMedDate not supplied

Long-term intermittent compressive stimulation improves the composition and mechanical properties of tissue-engineered cartilage.

Tissue engineering of articular cartilage is a promising alternative for cartilage repair. However, it has been difficult to develop tissue in vitro that mimicks native cartilage. Cartilaginous tissue formed in vitro does not accumulate enough extracellular matrix, is deficient in collagen, and possesses only a fraction of the mechanical properties of native cartilage. In this study, we investigated whether long-term intermittent compressive stimulation would improve the quality of the generated tissue. Chondrocyte cultures were established on the surface of porous calcium polyphosphate substrates and allowed to form cartilaginous tissue. In vitro-formed tissues were subjected to different stimulation protocols for 1 week. The optimal mechanical stimulation parameters identified in this short-term study were then applied to the cultures for up to 4 weeks. Mechanical stimulation applied at a 5% compressive amplitude at a frequency of 1 Hz for 400 cycles every second day resulted in the greatest increase in collagen synthesis (37 +/- 9% over control) while not significantly affecting proteoglycan synthesis (2 +/- 8% over control). This condition, applied to the chondrocyte cultures for 4 weeks, resulted in a significant increase in the amount of tissue that formed (stimulated, 2.4 +/- 0.2 mg dry wt; unstimulated, 1.61 +/- 0.08 mg dry wt). Stimulated tissues contained approximately 40% more collagen (stimulated, 590 +/- 58 microg; unstimulated, 420 +/- 42 microg), and 30% more proteoglycans (stimulated, 393 +/- 34 microg; unstimulated, 302 +/- 32 microg) as well as displaying a 2- to 3-fold increase in compressive mechanical properties (maximal equilibrium stress: stimulated, 10 +/- 1 kPa; unstimulated, 5 +/- 1 kPa; maximal equilibrium modulus: stimulated, 80 +/- 23 kPa; unstimulated, 24 +/- 6 kPa). The results of this study demonstrate that intermittent mechanical stimulation can increase collagen synthesis and, when applied over a 4-week period, can accelerate extracellular matrix accumulation as well as improve the material properties of the developed tissue. Interestingly, only short periods of mechanical stimulation (6 min every second day) were needed to affect the quality of cartilaginous tissue formed in vitro.

Adaptation, Physiological↗

PubMed1996

Interests and values in the Recommended Dietary Allowances and nutritional guidelines for Americans.

Evidence is provided showing that interests, values and belief systems have affected the development of Recommended Dietary Allowances (RDAs) and nutrition guidelines for Americans in the past and can be expected to do so in the future. The conflicts of the 1980s relative to the nutritional guidelines for Americans and the RDAs illustrate the tension among values that can parallel a conflict of interests. In the conflicts of the 1980s, we saw an apparent conflict between those policies that attempt to optimize outcomes for a large class of affected parties and those policies that attempt to establish constraints on actions which appear to threaten individual autonomy and freedom of choice. The former approach derives from utilitarian, consequential moral philosophy which evaluates policies by evaluating costs and harms, and weighing them against benefits to all parties. The latter has its strongest advocates in contemporary libertarianism which takes individual freedom to be the bottom line. Ethical vegetarianism, a belief system which would limit RDAs and guidelines to those that can be translated to vegan and other vegetarian diets, has been a more recent entry into the discussions. Such human value issues suggest that a set of RDAs or of nutrition guidelines is analogous to and may be considered to be an ethic. An ethic is a theory reached via the method of reflective equilibrium that is a coherent ordered triple set of beliefs: a set of considered moral judgments, a set of moral principles, and a set of relevant scientific background theories. The reasoning, however, can become circular and unsound when the considered moral judgments, moral principles and relevant background are not independent sources of information. If they are mixed or, for example, an intuition is mistaken for a scientific conclusion, the reasoning can be flawed.

Choice Behavior↗

PubMed1999

Oral ecology and person-to-person transmission of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis.

The ecological characteristics of the oral cavity are dissimilar for A. actinomycetemcomitans and for P. gingivalis, as judged by differences in their colonization preferences and patterns, associations with periodontal disease parameters, relationships with the subgingival microbiota and the type of periodontitis and their clonal persistence in the oral cavity. These features also suggest that as a periodontal pathogen, A. actinomycetemcomitans is different from P. gingivalis. Probably in most infected individuals, low levels of A. actinomycetemcomitans can persist for years in equilibrium with the host and the resident oral microbiota. However, it is well established that A. actinomycetemcomitans can cause disease in some individuals or in some circumstances when the regulatory mechanisms are unable to maintain homeostasis in the ecosystem. Elevated A. actinomycetemcomitans proportions of the biota can be regarded as a sign of ecological imbalance, leading to increased risk of periodontal destruction. There is also evidence showing elevated pathogenic potential of certain A. actinomycetemcomitans clones. Although A. actinomycetemcomitans seems to be relatively rarely transmitted between cohabiting adults, transmission can occur to periodontally healthy children of A. actinomycetemcomitans-positive parents. Parents and children may share factors that promote successful oral colonization of A. actinomycetemcomitans, or the window of opportunity is in childhood. Therefore, to prevent parent-child transmission of A. actinomycetemcomitans, bacterium-positive parents of young children are optimal targets for enhanced information and treatment. In selected populations, screening for specific clones of A. actinomycetemcomitans has been employed in prevention of peridontitis. Future research aiming at finding the reasons which cause the changes in the oral homeostasis to allow the growth of A. actinomycetemcomitans may give insight into novel prevention strategies for A. actinomycetemcomitans-associated periodontitis. Compared with A. actinomycetemcomitans, P. gingivalis shows a different pattern of coexistence with the host. In periodontal health or in children, P. gingivalis is absent or only rarely detected. When present, P. gingivalis is commonly recovered in high numbers from dentitions exhibiting inflamed periodontitis and poor oral hygiene. Contrary to A. actinomycetemcomitans, the data on the vertical transmission of P. gingivalis are limited. The major infection route of P. gingivalis seems to be between adults, indicating that P. gingivalis commonly colonizes in an established oral microbiota. These characteristics suggest that the degree of tolerance between P. gingivalis and the host is inferior to that between A. actinomycetemcomitans and the host. It appears that the association of P. gingivalis with disease is a rule rather than an accidental incident. On these grounds, it seems that the host-P. gingivalis relationship approaches antibiosis. Since P. gingivalis infection is related to a typical periodontal eco-pathology, the susceptibility to person-to-person transmission of this pathogen may be controlled by periodontal treatment and emphasizing the significance of high standard oral hygiene.

Actinobacillus Infections↗

PubMed1998

Synergy of the human spine in neutral postures.

The neutral position of the spine is the posture most commonly sustained throughout daily activities. Previous investigations of the spine focused mainly on maximal exertions in various symmetric and asymmetric postures. This report proposes a new synergetic approach for analysis of the spine in neutral postures and evaluates its performance. The model consists of passive components, the osteoligamentous spine, and active components, the spinal muscles. The muscle architecture includes 60 muscles inserting onto both the rib cage and lumbar vertebral bodies. The passive spine is simulated by a finite element model, while kinematic constraints and optimization are used for resolution of a redundant muscle recruitment problem. Although the passive spine alone exhibits little resistance to a vertical load, its load-bearing capacity in neutral posture is significantly enhanced by the muscles, i.e., the passive spine and its muscles must be considered as a synergetic system. The proposed method is used to investigate the response of the spine when the T1 vertebra displaces 40 mm anteriorly and 20 mm posteriorly from its initial position. The sacrum is fixed at all times and the T1 displacements are achieved by the action of muscles. The results suggest that relatively small muscle activations are sufficient to stabilize the spine in neutral posture under the body weight. The results also indicate that muscles attaching onto the rib cage are important for control of the overall spinal posture and maintenance of equilibrium. The muscles inserting onto the lumbar vertebrae are found mainly to enhance the stability of the spine. The proposed method also predicts forces and moments carried by the passive system. Flexion moments ranging from 8000 Nmm to 15,000 Nmm, corresponding to decreases in lordosis of 6 degrees and 7.5 degrees respectively, are found to be carried by the passive spine at the thoracolumbar junction when the T1 vertebra is 40 mm anterior to its initial position.

Finite Element Analysis↗

PubMed2006

Adsorption geometry and core excitation spectra of three phenylpropene isomers on Cu(111).

Theoretical C 1s near edge x-ray absorption fine structure (NEXAFS) spectra for the C(9)H(10) isomers trans-methylstyrene, alpha-methylstyrene, and allylbenzene in gas phase and adsorbed at Cu(111) surfaces have been obtained from density functional theory calculations where adsorbate geometries were determined by corresponding total energy optimizations. The three species show characteristic differences in widths and peak shapes of the lowest C 1s-->pi(*) transitions which are explained by different coupling of the pi-electron system of the C(6) ring with that of the side chain in the molecules as well as by the existence of nonequivalent carbon centers. The adsorbed molecules bind only weakly with the substrate which makes the use of theoretical NEXAFS spectra of the oriented free molecules meaningful for an interpretation of experimental angle-resolved NEXAFS spectra of the adsorbate systems obtained in this work. However, a detailed quantitative account of relative peak intensities requires theoretical angle-resolved NEXAFS spectra of the complete adsorbate systems which have been evaluated within the surface cluster approach. The comparison with experiment yields almost perfect agreement and confirms the reliability of the calculated equilibrium geometries of the adsorbates. This can help to explain observed differences in the catalytic epoxidation of the three molecules on Cu(111) based on purely geometric considerations.

Journal Article↗

PubMed1978

H + transport in urinary epithelia.

This review of urinary acidification is primarily based on studies in isolated epithelia such as the turtle bladder. Despite the lack of unambiguous proof, the wealth of indirect evidence suggests that the cause of bicarbonate absorption is H+ secretion into the lumen. The mechanisms that regulate H+ transport are discussed. The electrochemical gradient for protons across the membrane is found to be the most fundamental regulator not only of passive movement but also of active transport. CO2 and aldosterone stimulate H+ transport, the latter by a mechanism apparently separate from the effect of this hormone on sodium transport. Although carbonic anhydrase activity is important for optimal function of the H+ pump, the results with carbonic anhydrase inhibitors need to be interpreted with caution. The evidence for Na:H exchange is reviewed and found to be not very persuasive, The metabolic pathways that fuel H+ transport are found to be all the major energy-yielding reactions in the cell, but particular prominence is given to the new discovery of the role of the pentose shunt in energizing transport. Finally, I discuss the important role H+ transport in energy transduction in subcellular organelles.

Acid-Base Equilibrium↗

PubMed2001

Control of nitric oxide dynamics by guanylate cyclase in its activated state.

Soluble guanylate cyclase (sGC) is the target of nitric oxide (NO) released by nitric-oxide synthase in endothelial cells, inducing an increase of cGMP synthesis in response. This heterodimeric protein possesses a regulatory subunit carrying a heme where NO binding occurs, while the second subunit harbors the catalytic site. The binding of NO and the subsequent breaking of the bond between the proximal histidine and the heme-Fe(2+) are assumed to induce conformational changes, which are the origin of the catalytic activation. At the molecular level, the activation and deactivation mechanisms are unknown, as is the dynamics of NO once in the heme pocket. Using ultrafast time-resolved absorption spectroscopy, we measured the kinetics of NO rebinding to sGC after photodissociation. The main spectral transient in the Soret band does not match the equilibrium difference spectrum of NO-liganded minus unliganded sGC, and the geminate rebinding was found to be monoexponential and ultrafast (tau = 7.5 ps), with a relative amplitude close to unity (0.97). These characteristics, so far not observed in other hemoproteins, indicate that NO encounters a high energy barrier for escaping from the heme pocket once the His-Fe(2+) bond has been cleaved; this bond does not reform before NO recombination. The deactivation of isolated sGC cannot occur by only simple diffusion of NO from the heme; therefore, several allosteric states may be inferred, including a desensitized one, to induce NO release. Thus, besides the structural change leading to activation, a consequence of the decoupling of the proximal histidine may also be to induce a change of the heme pocket distal geometry, which raises the energy barrier for NO escape, optimizing the efficiency of NO trapping. The non-single exponential character of the NO picosecond rebinding coexists only with the presence of the protein structure surrounding the heme, and the single exponential rate observed in sGC is very likely to be due to a closed conformation of the heme pocket. Our results emphasize the physiological importance of NO geminate recombination in hemoproteins like nitric-oxide synthase and sGC and show that the protein structure controls NO dynamics in a manner adapted to their function. This control of ligand dynamics provides a regulation at molecular level in the function of these enzymes.

Allosteric Site↗

PubMed2006

Optimizing rumen functions in the close-up transition period and early lactation to drive dry matter intake and energy balance in cows.

The large deficit in energy intake in relation to energy requirements during the transition and early lactation periods means that high-producing cows need energy-dense rations. High-starch diets are intensively fermented by the microbial ecosystem in the rumen, giving rise to a high production of VFAs and resulting in a drop in pH and the accumulation of lactic acid, which exacerbates the decline in pH and is considered as the major cause of rumen acidosis. This rumen dysfunction affects rumen microbes and results in less efficient digestion, thereby decreasing feed intake and exacerbating the energy deficit in the cows. The main way to limit the risk of acidosis is by diet management. Thus, animals must be progressively adapted to grain ingredients during the 3-week period before calving. Furthermore, the diet management strategy will be to privilege low-degradable starch and include enough fiber in the diet to stimulate rumination and salivation. Chemical additives can be used to prevent rumen acidosis. Rumen pH can be controlled by direct addition of chemical buffers at doses of 1-2% of DM intake. Metabolic hydrogen can be mobilized through specific metabolic pathways such as propionogenesis to compete with the synthesis of lactic acid. This can be achieved by adding propionate precursors such as aspartate, malate or fumarate. However, these additives are not economically viable, and will not easily be accepted by consumers. Probiotics, which are mainly supplied as live yeasts, have to be regarded as a solution for preventing subacute acidosis but they are not considered as an efficient cure for acute acidosis. Although the mechanisms of action of probiotics are not fully understood, this paper proposes a plausible model of their mode of action. Recently, additives based on plant extracts have been proposed as a solution for optimizing rumen functions, but further efficacy studies and safety trials are required before these additives can be marketed. The addition of fibrolytic enzymes has been suggested to improve the digestion of the dietary fiber fraction during acidosis. Although the results obtained so far are encouraging, more ruminant-specific research needs to be carried out on these enzymes. Some antibiotics are potential inhibitors of Gram-positive bacteria, which are involved in rumen acidosis, but their use as feed additives has been banned from 01/01/2006 in the EU.

Acid-Base Equilibrium↗

PubMed1996

Acylation of pulmonary surfactant protein-C is required for its optimal surface active interactions with phospholipids.

This study investigates the importance of thioester-linked acyl groups in lung surfactant protein C (SP-C) in facilitating interactions with phospholipids that yield functionally important surface active behaviors. Native SP-C, palmitoylated at cysteine residues at positions 5 and 6, was isolated from bovine lung surfactant by liquid chromatography. Deacylated SP-C (dSP-C), unchanged in composition and sequence from SP-C but having a decreased alpha-helical content in films with dipalmitoyl phosphatidylcholine (DPPC) of 52 versus 70%, was obtained by treatment with 0.1 M sodium carbonate buffer at pH 10. Surface activity was studied for SP-C and dSP-C combined with column-purified phospholipids (PPL) from calf lung surfactant or with synthetic phospholipids (DPPC or a synthetic phospholipid mixture (SPL) containing 50:35:15, DPPC:egg phosphatidylcholine:egg phosphatidylglycerol). Interfacial measurements included surface pressure time adsorption isotherms for dispersed surfactants with diffusion minimized, dynamic surface pressure area isotherms and respreading for films in the Wilhelmy balance, and overall surface tension lowering at physiologic cycling rate in oscillating bubble experiments. Dispersions of PPL:SP-C and SPL:SP-C rapidly adsorbed to high equilibrium surface pressures of 47-48 mN/m, significantly better than corresponding dispersions containing dSP-C. The adsorption of PPL:dSP-C was essentially unchanged from that of PPL alone, and the adsorption of SPL:dSP-C was improved only slightly over SPL alone. In Wilhelmy balance studies, dynamic respreading was significantly improved over phospholipids alone in films of SP-C plus PPL, SPL, or DPPC. Respreading was improved less markedly by dSP-C in corresponding films with SPL or DPPC and not at all in films with PPL. Maximum surface pressures were also higher in cycled films of SP-C versus dSP-C combined with PPL or SPL. In bubble experiments (37 degrees C, 20 cycles/min), dispersions of PPL:SP-C and SPL:SP-C reached low minimum surface tensions of <1 and 5 mN/m, respectively, whereas PPL:dSP-C and SPL:dSP-C only reached minima of approximately 20 mN/m as did PPL and SPL alone. Acylation in SP-C is crucial for its interactions with phospholipids over the full spectrum of adsorption and dynamic surface behaviors important for lung surfactant.

Acylation↗

PubMed2004

A unifying concept of seizure onset and termination.

Recent discoveries in molecular biology and human genetics have contributed greatly to an understanding of the nature of seizure (ictal) activity. However, two questions of fundamental clinical importance continue to resist scientific inquiry: when and why does a seizure begin; and when and why does a seizure end? This paper cites evidence from the medical literature in support of two counterintuitive concepts that address this issue. First, that despite the diversity of conditions that are associated with seizures, the ictal response results from disturbances of a mitochondrial metabolic pathway that is common to them all. Second, that the seizure is not inherently harmful but is, instead, associated with massive intracerebral circulatory changes that are intended to restore impaired mitochondrial function. We hypothesize that the protogenic pathophysiological condition leading to neuronal hyperexitability and seizures results from inadequate mitochondrial energy production due to hypoxia or a hypoxia-equivalent state. Failure to generate sufficient adenosine triphosphate compromises ionic pump function and the ability to maintain neuronal homeostasis and stability. The seizure cascade is a heroic effort to perfuse the brain when local mechanisms fail to restore energy production and ionic equilibrium. In summary, a seizure starts when the neuron's aerobic machinery fails to maintain effective ionic pump function and terminates when increased cerebral perfusion, associated with the seizure response, restores adequate supplies of metabolic nutrients required for mitochondrial respiration. This unorthodox unifying concept that views ictogenesis as part of a restorative process rather than as a life threatening event may provide the basis for a much needed paradigm shift in the management of seizures. Current antiepileptic drugs are associated with many serious side effects, including death, and fail to control seizures in 20% of patients with primary generalized epilepsy and 35% of patients with partial epilepsy. We propose that efforts to prevent and control seizures should be directed away from pharma-chemical suppression towards removing the causes of disturbed neuronal energy production and developing methods and bioactive agents that promote an optimized physiological milieu within the brain.

Adenosine Triphosphate↗

PubMed2006

Effusive molecular beam study of C2H6 dissociation on Pt(111).

The dissociative sticking coefficient for C2H6 on Pt(111) has been measured as a function of both gas temperature (Tg) and surface temperature (Ts) using effusive molecular beam and angle-integrated ambient gas dosing methods. A microcanonical unimolecular rate theory (MURT) model of the reactive system is used to extract transition state properties from the data as well as to compare our data directly with supersonic molecular beam and thermal equilibrium sticking measurements. We report for the first time the threshold energy for dissociation, E0 = 26.5 +/- 3 kJ mol(-1). This value is only weakly dependent on the other two parameters of the model. A strong surface temperature dependence in the initial sticking coefficient is observed; however, the relatively weak dependence on gas temperature indicates some combination of the following (i) not all molecular excitations are contributing equally to the enhancement of sticking, (ii) that strong entropic effects in the dissociative transition state are leading to unusually high vibrational frequencies in the transition state, and (iii) energy transfer from gas-phase rovibrational modes to the surface is surprisingly efficient. In other words, it appears that vibrational mode-specific behavior and/or molecular rotations may play stronger roles in the dissociative adsorption of C2H6 than they do for CH4. The MURT with an optimized parameter set provides for a predictive understanding of the kinetics of this C-H bond activation reaction, that is, it allows us to predict the dissociative sticking coefficient of C2H6 on Pt(111) for any combination of Ts and Tg even if the two are not equal to one another.

Journal Article↗

PubMed2001

Arginine-140 and isoleucine-141 determine the 17beta-estradiol-binding specificity of the sex-steroid-binding protein (SBP, or SHBG) of human plasma.

Arginine-140 and isoleucine-141 were identified as key determinants of 17beta-estradiol (E(2)) binding affinity of the sex-steroid-binding protein (SBP, or SHBG) of human plasma. Amino acid residues that differ between human and rabbit SBP sequences were replaced in the human protein and the products tested for lowered E(2)binding activity as are seen in the rabbit protein. Only mutants containing either R140K or I141L replacements display an E(2) equilibrium dissociation constant (Kd) higher than the wild type, reaching a value of 30 nM when both were present. The 5alpha-dihydrotestosterone (DHT) equilibrium dissociation constant of these mutants was unaffected. The quadruple mutant M107I/I138V/R140K/I141L yielded an E(2) Kd of 65 nM, significantly closer to the 80 nM rabbit SBP E(2) Kd value. Although mutants containing the M107I and I138V replacements in the absence of R140K and I141L had normal E(2) Kds, the presence of the M107I replacement in the quadruple mutant was necessary to obtain an accurate E(2) Kd value by competitive Scatchard analysis. Molecular modeling using coordinates for the recently determined N-terminal domain of human SBP revealed a significant shift of the F56 phenyl ring away from ring A of E(2) in mutant models containing the R140K and I141L replacements. We conclude that R140 and I141 are required for sustaining the right proximity of the phenyl ring of F56 to ring A of 17beta-estradiol, thus optimizing the E(2)-binding affinity of human SBP.

Amino Acid Sequence↗