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Dynamical control: comparison of map and continuous-flow approaches.

Continuous and pulsed forms of control of a multistable system are compared directly, both theoretically and numerically, taking as an example the switching of a periodically driven class-B laser between its stable and unstable pulsing regimes. It is shown that continuous control is the more energy efficient. This result is illuminated by making use of the close correspondence that exists between the problems of energy-optimal control and the stability of a steady state.

Lasers↗

New model for the hydroxyapatite-octacalcium phosphate interface.

Some experimental results have indicated that hydroxyapatite (HA) and octacalcium phosphate (OCP) can form an epitaxic interface. Subsequently the OCP-HA interface has become of great biological interest in the context of mineralized tissue formation. In this work a new OCP-HA interface model based on Brown's proposed configuration [Brown (1962), Nature, 197, 1048-1050] and using the minimum interface free-energy optimization is presented. This new model is formed by half a unit cell of HA and one unit cell of OCP, as in Brown's model, but in our case [1-210] of HA is 'glued' with [010] of OCP. Therefore, the relationship found was: [000-1](HA) parallel to [001](OCP) and [1-210](HA) parallel to [010](OCP). Self-consistent field methods were used for the analysis of Brown's model and ours. It is shown that the atoms in our model have similar environments as in the HA and OCP unit cells and that, as a result of the differences between HA and OCP unit-cell parameters, this interface presents misfit-dislocation-like features. High-resolution transmission electron microscopy (HREM) simulated images for the new interface model have been included and, when they are compared with the experimental ones, the similarity is quite good.

Journal Article↗

Stoichiometry of lipid interactions with transmembrane proteins--Deduced from the 3D structures.

The stoichiometry of the first shell of lipids interacting with a transmembrane protein is defined operationally by the population of spin-labeled lipid chains whose motion is restricted directly by the protein. Interaction stoichiometries have been determined experimentally for a wide range of alpha-helical integral membrane proteins by using spin-label ESR spectroscopy. Here, we determine the spatially defined number of first-shell lipids at the hydrophobic perimeter of integral membrane proteins whose 3D structure has been determined by X-ray crystallography and lipid-protein interactions characterized by spin-labeling. Molecular modeling is used to build a single shell of lipids surrounding transmembrane structures derived from the PDB. Constrained energy optimization of the protein-lipid assemblies is performed by molecular mechanics. For relatively small proteins (up to 7-12 transmembrane helices), the geometrical first shell corresponds to that defined experimentally by perturbation of the lipid-chain dynamics. For larger, multi-subunit alpha-helical proteins, the lipids perturbed directly by the protein may either exceed or be less in number than those that can be accommodated at the intramembranous perimeter. In these latter cases, the motionally restricted spin-labeled lipids can be augmented by intercalation, or can correspond to a specific subpopulation at the protein interface, respectively. For monomeric beta-barrel proteins, the geometrical lipid stoichiometry corresponds to that determined from lipid mobility for a 22-stranded barrel, but fewer lipids are motionally restricted than can be accommodated around an eight-stranded barrel. Deviations from the geometrical first shell, in the beta-barrel case, are for the smaller protein with a highly curved barrel.

Bacterial Outer Membrane Proteins↗

A new force-field program for the calculation of glycopeptides and its application to a heptacosapeptide-decasaccharide of immunoglobulin G1. Importance of 1-6-glycosidic linkages in carbohydrate.peptide interactions.

Energetically favored conformations of glycopeptide 1 were calculated using the newly developed force-field program, GEGOP (geometry of glycopeptides). The three-dimensional structure of glycopeptide 1, which is part of the Fc fragment of IgG1, has been calculated. 1 contains 27 amino acid residues from Pro291 to Lys317 and a biantennary decasaccharide N-linked to Asn297. The conformations of the peptide and the carbohydrate parts are shown to be mutually dependent. Single glycosyl residues of 1 exhibit interaction energies of up to -31.8 kJ/mol with the peptide portion. Generally, only a few of the glycosyl residues of the oligosaccharide moiety express significant interaction energies with the peptide part. No easy prediction is possible of glycosyl residues which exhibit favorable interaction energies. However, in all of the calculated structures, the glycosyl residues of the 1-6-linked branches show strong attractive forces for the peptide part. 1-6-glycosidically linked branches can adopt a larger number of conformations than other linkages due to their high flexibility which allows more favorable interactions with proteins. We developed the GEGOP program in order to be able to study the preferred conformations of large glycopeptides. The program is based on the GESA (geometry of saccharides) program and utilizes the HSEA (hard sphere exo anomeric) force field for the carbohydrate part and the ECEPP/2 (empirical conformation energy program for peptides) force field [Némethy, G., Pottle, M. S. & Scheraga, H. A. (1983) J. Phys. Chem. 87, 1883-1887] for the peptide part. The GEGOP program allows the simultaneous relaxation of all rotational degrees of freedom of these glycoconjugates during the energy optimization process. Thus, mutual interactions between glycosyl and amino acid residues can be studied in detail.

Carbohydrate Conformation↗

Inactivation of the Pseudomonas putida cytochrome o ubiquinol oxidase leads to a significant change in the transcriptome and to increased expression of the CIO and cbb3-1 terminal oxidases.

Pseudomonas putida KT2440 contains a branched aerobic respiratory chain with several terminal oxidases. Inactivation of the cyo terminal ubiquinol oxidase has little effect on growth rate but is known to relieve the inhibition by global control that modulates induction of genes required to assimilate alkanes in cells growing in the presence of preferred carbon sources. We show that inactivation of other terminal oxidases has no effect on regulation of the alkane degradation pathway, which points to cyo as the oxidase that transmits a regulatory signal related to the activity of the electron transport chain. Using a genome-wide DNA microarray we found that inactivation of cyo has a significant effect on the transcriptome, supporting that it participates in global regulation of gene expression. Among the genes affected stand out those coding for transporters of organic acids, porins, transcriptional regulators and terminal oxidases. Real-time reverse transcription polymerase chain reaction (RT-PCR) showed that, in cells growing exponentially in a complete medium, the absence of cyo was compensated by increased expression of the cyanide-insensitive and cbb3-1 terminal oxidases, while cbb3-2 and aa3 oxidases remained unaffected. When cells enter into stationary phase cyo levels decrease and inhibition of the alkane degradation genes ceases. This was paralleled by upregulation of the cyanide-insensitive, cbb3-1, cbb3-2 and aa3 terminal oxidases. The results suggest that P. putida adapts the composition of the electron transport chain not only to optimize energy generation, but also to influence the transcriptome profile of the cell through global control of gene expression.

Alkanes↗

F-actin stabilization increases tension cost during contraction of permeabilized airway smooth muscle in dogs.

1. Dynamic actin reorganization involving actin polymerization and depolymerization may play an important functional role in smooth muscle. 2. This study tested the hypothesis that F-actin stabilization by phalloidin increases tension cost (i.e. ATP hydrolysis rate per unit of isometric force) during Ca2+-induced activation of Triton X-100-permeabilized canine tracheal smooth muscle. 3. Adenosine 5'-triphosphate (ATP) hydrolysis rate was quantified using an enzyme-coupled NADH fluorometric technique, regulatory myosin light chain (rMLC) phosphorylation was measured by Western blot analysis, and maximum unloaded shortening velocity (Vmax) was estimated by interpolation of the force-velocity relationship to zero load during isotonic loading. 4. Maximal activation with 10 microM free Ca2+ induced sustained increases in isometric force, stiffness, and rMLC phosphorylation. However, the increase in ATP hydrolysis rate initially reached peak values, but then declined to steady-state levels above that of the unstimulated muscle. Thus, tension cost decreased throughout steady-state isometric force. 5. Following incubation of permeabilized strips with 50 microM phalloidin for 1 h, the increases in isometric force and stiffness were not sustained despite a sustained increase in rMLC phosphorylation. Also, after an initial decline, tension cost increased throughout activation. Phalloidin had no effect on Vmax during steady-state isometric force or on rMLC phosphorylation. 6. These findings suggest that dynamic reorganization of actin is necessary for optimal energy utilization during contraction of permeabilized airway smooth muscle.

Actins↗

Dual chamber pacing with a single-lead DDD pacing system.

The successful application of single-lead VDD pacing during the last few years has generated the idea of single-lead DDD pacing. Preliminary data from several single-lead VDD studies attempting to pace the atrium by a floating atrial dipole are unsatisfactory, causing an unacceptably high current drain of the device. We studied the feasibility as well as the short- and long-term stability of atrioventricular sequential pacing, using a new single-pass, tined DDD lead. In eight consecutive patients (age 73+/-16 years) with symptomatic higher degree AV block and intact sinus node function, this new single-pass DDD lead was implanted in combination with a DDDR pacemaker. Correct VDD and DDD function was studied at implantation; at discharge; and at 1, 3, and 6 months of follow-up. At implant, the atrial stimulation threshold was 0.6+/-0.1 V/0.5 ms. During follow-up, the atrial pacing thresholds in different every day positions averaged 2.1+/-0.5 V at discharge, 2.9+/-0.5 V at 1 month, 3.8+/-0.4 V at 3 months, and 3.4+/-0.4 V at 6 months (pulse width always 0.5 ms). The measured P wave amplitude at implantation was 4.5+/-2.2 mV; during follow-up the telemetered atrial sensitivity thresholds averaged 2.1+/-0.3 mV. Phrenic nerve stimulation at high output pacing (5.0 V/0.5 ms) was observed in three (38%) patients at discharge and in one (13%) patient during follow-up; an intermittent unmeasurable atrial lead impedance at 3 and 6 months follow-up was documented in one (13%) patient. This study confirms the possibility of short- and long-term DDD pacing using a single-pass DDD lead. Since atrial stimulation thresholds are still relatively high compared to conventional dual-lead DDD pacing, further improvements of the atrial electrodes are desirable, enabling lower pacing thresholds and optimizing energy requirements as well as minimizing the potential disadvantage of phrenic nerve stimulation.

Aged↗

Enhanced preservation of acutely ischemic myocardium using glucose-insulin-potassium solutions.

"Surgical myocardial stunning" represents a model of both ischemia and infarction that unlike regular "stunning" has the potential for permanent or partially reversible cellular function. While substrate enhancement may not play an important role in myocardial stunning, it may be critical during surgical stunning when mitochondrial dysfunction is present. The primary myocardial substrate for the normal myocardium is free fatty acids; however, this may not be the optimal energy source for the ischemic heart. Exogenous glucose appears to be a superior substrate during periods of myocardial ischemia. Glucose-insulin-potassium (GIK) solutions appear to have an important role in the revascularization of acutely ischemic myocardium. In isolated hearts with regional ischemia, GIK was shown to decrease infarct size, increase ATP and creatine phosphate levels, and improve ventricular function. GIK appears to protect the ischemic myocardium by preserving cellular function and improving myocardial perfusion. Our preliminary experimental studies indicate that GIK may effectively reduce necrosis and stunning in a model of acute surgical revascularization.

Animals↗

Generation of torsional and vertical eye position signals by the interstitial nucleus of Cajal.

The neural integrator, which converts eye velocity signals into position signals, is central to oculomotor theory. Similar integrators are probably necessary in any neural system that changes and maintains muscular tension. The integrator for horizontal eye position is in the pons, but the locations of the vertical and torsional integrators have not been clearly defined. Recording three-dimensional eye movements in alert monkeys during microstimulation and pharmacological inactivation of midbrain sites showed that the interstitial nucleus of Cajal generates both the torsional and vertical eye position signals. Up and down signals are linked with clockwise signals in the right brain and counterclockwise signals in the left brain. This three-dimensional coordinate system achieves orthogonality and bilateral symmetry without redundancy and optimizes energy efficiency for horizontal visual scanning.

Animals↗

The bovine leukemia virus encapsidation signal is composed of RNA secondary structures.

The encapsidation signal of bovine leukemia virus (BLV) was previously shown by deletion analysis to be discontinuous and to extend into the 5' end of the gag gene (L. Mansky et al., J. Virol. 69:3282-3289, 1995). The global minimum-energy optimal folding for the entire BLV RNA, including the previously mapped primary and secondary encapsidation signal regions, was analyzed. Two stable stem-loop structures (located just downstream of the gag start codon) were predicted within the primary signal region, and one stable stem-loop structure (in the gag gene) was predicted in the secondary signal region. Based on these predicted structures, we introduced a series of mutations into the primary and secondary encapsidation signals in order to explore the sequence and structural information contained within these regions. The replication efficiency and levels of cytoplasmic and virion RNA were analyzed for these mutants. Mutations that disrupted either or both of the predicted stem-loop structures of the primary signal reduced the replication efficiency by factors of 7 and 40, respectively; similar reductions in RNA encapsidation efficiency were observed. The mutant with both stem-loop structures disrupted had a phenotype similar to that of a mutant containing a deletion of the entire primary signal region. Mutations that disrupted the predicted stem-loop structure of the secondary signal led to similar reductions (factors of 4 to 6) in both the replication and RNA encapsidation efficiencies. The introduction of compensatory mutations into mutants from both the primary and secondary signal regions, which restored the predicted stem-loop structures, led to levels of replication and RNA encapsidation comparable to those of virus containing the wild-type encapsidation signal. Replacement of the BLV RNA region containing the primary and secondary encapsidation signals with a similar region from human T-cell leukemia virus (HTLV) type 1 or type 2 led to virus replication at three-quarters or one-fifth of the level of the parental virus, respectively. The results from both the compensatory mutants and BLV-HTLV chimeras indicate that the encapsidation sequences are recognized largely by their secondary or tertiary structures.

Animals↗

Investigating evolutionary lines of least resistance using the inverse protein-folding problem.

We present a polynomial time algorithm for estimating optimal HP sequences that fold to a specified target protein conformation based on Sun et al's Grand Canonical (GC) model. Application of the algorithm to related proteins taken from the PDB allows us to explore the nature of the protein genotype:phenotype map. Results suggest: (1) that the GC model captures important biological aspects of the mapping between protein sequences and their corresponding structures, and (2) the set of sequences that map to a target structure with optimal energy is affected by minor differences in structure.

Algorithms↗

EEG alpha blocking correlated with perception of inner light during zen meditation.

According to the experimental results and practitioners' subjective experience, we report some hypotheses that may account for meditative phenomena during the practice of Zen-Buddhism. Orthodox Zen-Buddhist practitioners, aiming to prove the most original true-self, discover and uncover the inner energy or light on the way towards their goal. Perception of the inner light can be comprehended as resonance. Uncovering the inner energy optimizes physiological and mental health. In the meditation experiment, a significant correlation was observed between perception of the inner light and electroencephalographic (EEG) alpha blockage. We further examined this phenomenon by recording the EEG from subjects during a blessing that the subjects did not know being given. During the blessing period, significant alpha blocking was observed in experimental subjects who had been practicing meditation for years in preparation for being in resonance with the inner light. This report provides a new insight into the debate that meditation benefits our health.

Adult↗

Muscle creatine uptake and creatine transporter expression in response to creatine supplementation and depletion.

The total creatine pool size [Cr(total); creatine (Cr) + phosphocreatine (PCr)] is crucial for optimal energy utilization in skeletal muscle, especially at the onset of exercise and during intense contractions. The Cr(total) likely is controlled by long-term modulation of Cr uptake via the sodium-dependent Cr transporter (CrT). To test this hypothesis, adult male Sprague-Dawley rats were fed 1% Cr, their muscle Cr(total) was reduced by approximately 85% [1% beta-guanidinoproprionic acid (beta-GPA)], or their muscle Cr(total) was repleted (1% Cr after beta-GPA depletion). Cr uptake was assessed by skeletal muscle (14)C-Cr accumulation to Cr and PCr by using hindlimb perfusion, and CrT protein content was assessed by Western blot. Cr uptake rate decreased with dietary Cr supplementation in the white gastrocnemius (WG; 45%) only. Depletion of muscle Cr(total) to approximately 15% of normal increased Cr uptake in the soleus (21%) and red gastrocnemius (22%), corresponding to 70-150% increases in muscle CrT content. In contrast, the inherently lower Cr uptake rate in the WG was unchanged with depletion of muscle Cr(total) even though CrT band density was increased by 230%. Thus there was no direct relationship between apparent muscle CrT abundance and Cr uptake rates. However, Cr uptake rates scaled inversely with decreases in muscle Cr(total) in the high-oxidative muscle types but not in the WG. This implies that factors controlling Cr uptake are different among fiber types. These observations may help explain the influence of initial muscle Cr(total), time dependency, and variations in muscle Cr(total) accumulation during Cr supplementation.

Animals↗

Effects of flotation-restricted environmental stimulation technique on stress-related muscle pain: what makes the difference in therapy--attention-placebo or the relaxation response?

INTRODUCTION: The purpose of the present study was to examine the potential effects of attention-placebo on flotation tank therapy. Flotation-restricted environmental stimulation technique is a method whereby an individual lies in a floating tank and all stimuli are reduced to a minimum. METHODS: Thirty-two patients were diagnosed as having stress-related muscular pain. In addition, 16 of the participants had received the diagnosis of burnout depression. The patients were treated with flotation-restricted environmental stimulation technique for six weeks. One-half of the patients were also given special attention for 12 weeks (high attention), while the remainder received attention for only six weeks (normal attention). RESULTS: The participants exhibited lowered blood pressure, reduced pain, anxiety, depression, stress and negative affectivity, as well as increased optimism, energy and positive affectivity. The results were largely unaffected by the degree of attention-placebo or diagnosis. CONCLUSION: It was concluded that flotation therapy is an effective, noninvasive method for treating stress-related pain, and that the method is not more affected by placebo than by other methods currently used in pain treatment. The treatment of both burnout depression and pain related to muscle tension constitutes a major challenge for the patient as well as the care provider, an area in which great gains can be made if the treatment is effective. Flotation therapy may constitute an integral part of such treatment.

Attention↗

Scale and translation invariant minimum average correlation energy filter.

A new type, to our knowledge, of scale and translation invariant correlation filter is described. Its form in polar coordinates generalizes the forms of the one-decomposition-term filters. That is combined with the minimum-average-correlation-energy optimization method to suppress the sidelobes and achieve correlation peaks. A theoretical analysis as well as a detailed explanation of the computational procedure is provided. The concept is tested on five interferometric images of 256 gray levels without preprocessing. The computed filter gives correlation peaks for reference image scales in the range of 0.3/4.0 (minimal scale: maximal scale = 1:13). The discrimination ability of the filter is investigated-no false peak occurred. The filter works in the background so that there is no need for input image segmentation. A method for extension is described to calculate a filter for more than one reference image.

Journal Article↗

Complementary study of differential absorption lidar optimization in direct and heterodyne detections.

A detailed study using both analytical and numerical calculations of direct and heterodyne differential absorption lidar (DIAL) techniques is conducted to complement previous studies. The DIAL measurement errors depend on key experimental parameters, some of which can be adjusted to minimize the statistical error. Accordingly, the pertinent criteria on optical thickness, the number of photons emitted at the on and off wavelengths, are discussed to reduce the relative error on the total column content or range-resolved measurements that rely on either hard target or atmospheric backscatter returns. In direct detection, the optimal optical thickness decreases from 1.3 to 0.8 when the background increases while the on-line-to-off-line optimal energy ratio decreases from 3.6 to 2.7. In heterodyne detection, the minimum error is obtained for an optical thickness of 1.2 and an energy ratio of 4.3.

Journal Article↗

Multiple-sensor systems for physiologic cardiac pacing.

PURPOSE: To review the status of artificial sensors in cardiac pacemakers and the rationale for developing pacing systems that use multiple sensors. DATA SOURCES: Journal articles published between 1982 and 1993 indexed in MEDLINE using the keywords pacemakers, sensors, and rate-adaptive, as well as abstracts and articles in the authors' personal files. STUDY SELECTION: Articles describing clinical experience with or clinical evaluation of cardiac pacing systems using multiple artificial sensors. DATA SYNTHESIS: Artificial sensors were created to adjust pacing rate reliably in response to changes in levels of physical exertion for patients with sinoatrial disease in whom exercise heart rate response is inadequate (for example, chronotropic incompetence in sinoatrial disease). To achieve this, various artificial sensors were developed and many reports confirm improved exertional tolerance. More recently, sensors have assumed a greater role in cardiac pacemakers. For example, sensors are used to permit automatic adjustment of certain programmable pacemaker settings, such as the atrioventricular interval. In the future, they may also be used to maximize pacemaker longevity by automatically optimizing energy output (voltage, pulse width). No single sensor is ideal for all potential applications, and investigators have advocated using two or more sensors. Several pacemakers that use multiple sensors with different but complementary operating characteristics are already commercially available outside the United States. Although preliminary findings are encouraging, additional clinical experience with these pacemakers is needed to determine their ultimate role in clinical practice. CONCLUSION: Simultaneous use of multiple complementary artificial sensors may permit development of cardiac pacemakers that operate more physiologically yet require less specialized medical follow-up.

Clinical Trials as Topic↗

[Psychological, nutritional, socioeconomic aspects and family relations of Mexican children with low school performance].

Two groups of children (aged 4-6 years) living in poor urban areas of Hermosillo (Sonora) and having "low" and "adequate" school achievements, were studied with the objective of determining their psychological, social, economic and nutritional characteristics. They were evaluated by means of standardized psychological tests. Their nutritional condition was assessed by dietary anthropometric and biochemical indicators. The socioeconomic characteristics of their micro-environment were also determined including the degree of home stimulation. It was found that school performance does not depend solely from their execution in psychological tests (Intelligence Quotient and visuomotor and linguistic performance) but also from other micro-environmental factors. The children with "low"school performance were characterized by sub-optimal energy intakes, mild-to-moderate undernutrition, belonged to large families, lived under more crowded conditions, and had a low level of home stimulation. It is concluded that poor nutrition and a disadvantageous micro-environment particularly home stimulation) are important factors related to the poor school performance of the children studied.

Achievement↗