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Efficacy of training program for ambulatory competence in elderly women.

The optimal prevention of osteoporotic fractures in the elderly consists of increasing the bone density and preventing falls. We report on the efficacy of training program to promote ambulatory competence in elderly women. Twenty-five elderly women were enrolled in our training program, which is a three-month program consisting of dynamic balance training with Galileo 900 (Novotec, Pforzheim, Germany) once a week, combined with daily static balance (standing on one leg like a flamingo) and resistance (half-squat) training. The mean age of the participants was 72.8 years (range, 61-86 years). After 3 months of training, the step length, knee extensor muscle strength, and maximum standing time on one leg were significantly increased, while the walking speed and hip flexor muscle strength were not significantly altered. During the study period, no serious adverse events such as new vertebral fractures or adverse cardiovascular symptoms were observed in any participant. The present preliminary study shows that our training program may have the potential to promote ambulatory competence in elderly women.

Age Factors↗

Conformational sampling by NMR solution structures calculated with the program DIANA evaluated by comparison with long-time molecular dynamics calculations in explicit water.

The NMR solution structure of bovine pancreatic trypsin inhibitor (BPTI) obtained by distance geometry calculations with the program DIANA is compared with groups of conformers generated by molecular dynamics (MD) simulations in explicit water at ambient temperature and pressure. The MD simulations started from a single conformer and were free or restrained either by the experimental NOE distance restraints or by time-averaged restraints; the groups of conformers were collected either in 10 ps intervals during 200 ps periods of simulation, or in 50 ps intervals during a 1 ns period of simulation. Overall, these comparisons show that the standard protein structure determination protocol with the program DIANA provides a picture of the protein structure that is in agreement with MD simulations using "realistic" potential functions over a nanosecond timescale. For well-constrained molecular regions there is a trend in the free MD simulation of duration 1 ns that the sampling of the conformation space is slightly increased relative to the DIANA calculations. In contrast, for surface-exposed side-chains that are less extensively constrained by the NMR data, the DIANA conformers tend to sample larger regions of conformational space than conformers selected from any of the MD trajectories. Additional insights into the behavior of surface side-chains come from comparison of the MD runs of 200 ps or 1 ns duration. In this time range the sampling of conformation space by the protein surface depends strongly on the length of the simulation, which indicates that significant side-chain transitions occur on the nanosecond timescale and that much longer simulations will be needed to obtain statistically significant data on side-chain dynamics.

Amino Acid Sequence↗

Conformational flexibility of beta-secretase: molecular dynamics simulation and essential dynamics analysis.

AIM: Based on the structural analysis to reveal the mechanism of ligand binding to beta-secretase and the specificity of each binding sub-site. METHODS: Molecular dynamics was used to simulate on the ligand free beta-secretase and ligand bound beta-secretase. The trajectories were analyzed using the essential dynamics, and the significant conformational change was illustrated employing the DynDom program. RESULTS: The essential dynamics and DynDom analyses clearly showed that the beta-secretase experienced a large conformational change upon the substrate or inhibitor binding. The flap structure adopted a swing motion, gradually covering the active site to facilitate the ligand binding process. Residues Ser86 and Ile87 served as the hinge point. Inhibitor-enzyme interaction analysis revealed that residues at P2, P1, and P1' positions of the inhibitor were very important for the binding, and residues at P2' and P3' positions may be modified to improve the binding specificity. S3 subsite of the enzyme still had space to modify the inhibitors in increasing the binding affinity. CONCLUSION: The information presented here is valuable and could be used to identify small molecular inhibitors of beta-secretase.

Amyloid Precursor Protein Secretases↗

CAMDAS: an automated conformational analysis system using molecular dynamics. Conformational Analyzer with Molecular Dynamics And Sampling.

We present an automated conformational analysis program, CAMDAS (Conformational Analyzer with Molecular Dynamics And Sampling). CAMDAS performs molecular dynamics (MD) calculations for a target molecule and samples conformers from the trajectory of the MD. The program then evaluates the similarities between each of the sampled conformers in terms of the root-mean-square deviations of the atomic positions, clusters similar conformers, and finally prints out the clustered conformers. This MD-based conformational analysis is a broadly used method, and CAMDAS is intended to provide a convenient framework for the method. CAMDAS has the ability to find the representative conformers automatically from an arbitrarily given structure of the molecule. The accuracy of the program was examined using N-acetylalanine-N'-methylamide, and the obtained result was consistent with that of the systematic search method. In the test calculation of cyclodecane, CAMDAS could identify most of the known conformers and their conformational enantiomers by examining only 5000 conformers. In addition, the potential-scaled method, which we have developed previously as an accelerating technique for MD, could find two additional conformers of cyclodecane that have not been reported. CAMDAS presents a convenient way to find the energetically possible conformers of a molecule, which is needed especially in the early stage of drug design.

Alanine↗

Dynamic particle image velocimetry flow analysis of the flow field immediately downstream of bileaflet mechanical mitral prostheses.

New dynamic particle image velocimetry (PIV) technology was applied to the study of the flow field associated with prosthetic heart valves. Four bileaflet prostheses, the St. Jude Medical (SJM) valve, the On-X valve with straight leaflets, the Jyros (JR) valve, and the Edwards MIRA (MIRA) valve with curved leaflets, were tested in the mitral position under pulsatile flow conditions to find the effect of the leaflet shape and overall valve design on the flow field, particularly in terms of the turbulent stress distribution, which may influence hemolysis, platelet activation, and thrombus formation. Comparison of the time-resolved flow fields associated with the opening, accelerating, peak, and closing phases of the diastolic flow revealed the effects of the leaflet shape and overall valve design on the flow field. Anatomically and antianatomically oriented bileaflet valves were also compared in the mitral position to study the effects of the orientation on the downstream flow field. The experimental program used a dynamic PIV system utilizing a high-speed, high-resolution video camera to map the true time-resolved velocity field inside the simulated ventricle. Based on the experimental data, the following general conclusions can be made. High-resolution dynamic PIV can capture true chronological changes in the velocity and turbulence fields. In the vertical measuring plane that passes the centers of both the aortic and mitral valves (A-A section), bileaflet valves show clear and simple circulatory flow patterns when the valve is installed in the antianatomical orientation. The SJM, the On-X, and the MIRA valves maintain a relatively high velocity through the central orifice. The curved leaflets of the JR valve generate higher velocities with a divergent flow during the accelerating and peak flow phases when the valve is installed in the anatomical orientation. In the velocity field directly below the mitral valve and normal to the previous measuring plane (B-B section), where characteristic differences in valve design on the three-dimensional flow should be visible, the symmetrical divergent nature of the flow generated by the two inclined half-disks installed in the antianatomical orientation was evident. The SJM valve, with a central downward flow near the valve, is contrasted with the JR valve, which has a peripherally strong downward circulation with higher turbulent stresses. The On-X valve has a strong central downward flow attributable to its large opening angle and flared inlet shape. The MIRA valve also has a relatively strong downward central flow. The MIRA valve, however, diverts the flow three-dimensionally due to its peripherally curved leaflets.

Heart Valve Prosthesis↗

Dynamic histone modifications mark sex chromosome inactivation and reactivation during mammalian spermatogenesis.

Based on the formation of the XY body at pachytene and expression studies of a few X-linked genes, the X and Y chromosomes seem to undergo transcriptional inactivation during mammalian spermatogenesis. However, the extent and the mechanism of X and Y inactivation are not known. Here, we show that both the X and Y chromosomes undergo sequential changes in their histone modifications beginning at the pachytene stage of meiosis. These changes usually are associated with transcriptional inactivation in somatic cells, and they coincide with the exclusion of the phosphorylated (active) form of RNA polymerase II from the XY body. Both sex chromosomes undergo extensive deacetylation at histones H3 and H4 and (di)methylation of lysine (K)9 on histone H3; however, there are no changes in H3-K4 methylation. These changes persist even when the XY body disappears in late pachytene, and the X and Y chromosomes segregate from one another after the first meiotic division. By the spermatid stage, histone modifications of the X and Y chromosomes revert to those of active chromatin and RNA polymerase II reengages with both chromosomes. Our observations indicate that X and Y inactivation is extensive and persists even when the X and Y chromosomes are separated in secondary spermatocytes. These findings provide insights into epigenetic programming and chromatin dynamics in the male germ line.

Acetylation↗

A dynamic mathematical model to clarify signaling circuitry underlying programmed cell death control in Arabidopsis disease resistance.

Plant cells undergo programmed cell death in response to invading pathogens. This cell death limits the spread of the infection and triggers whole plant antimicrobial and immune responses. The signaling network connecting molecular recognition of pathogens to these responses is a prime target for manipulation in genetic engineering strategies designed to improve crop plant disease resistance. Moreover, as alterations to metabolism can be misinterpreted as pathogen infection, successful plant metabolic engineering will ultimately depend on controlling these signaling pathways to avoid inadvertent activation of cell death. Programmed cell death resulting from infection of Arabidopsis thaliana with Pseudomonas syringae bacterial pathogens was chosen as a model system. Signaling circuitry hypotheses in this model system were tested by construction of a differential-equations-based mathematical model. Model-based simulations of time evolution of signaling components matched experimental measurements of programmed cell death and associated signaling components obtained in a companion study. Simulation of systems-level consequences of mutations used in laboratory studies led to two major improvements in understanding of signaling circuitry: (1) Simulations supported experimental evidence that a negative feedback loop in salicylic acid biosynthesis postulated by others does not exist. (2) Simulations showed that a second negative regulatory circuit for which there was strong experimental support did not affect one of two pathways leading to programmed cell death. Simulations also generated testable predictions to guide future experiments. Additional testable hypotheses were generated by results of individually varying each model parameter over 2 orders of magnitude that predicted biologically important changes to system dynamics. These predictions will be tested in future laboratory studies designed to further elucidate the signaling network control structure.

Apoptosis↗

Automated assignment of NOESY NMR spectra using a knowledge based method (KNOWNOE).

Automated assignment of NOESY spectra is a prerequisite for automated structure determination of biological macromolecules. With the program KNOWNOE we present a novel, knowledge based approach to this problem. KNOWNOE is devised to work directly with the experimental spectra without interference of an expert. Besides making use of routines already implemented in AUREMOL, it contains as a central part a knowledge driven Bayesian algorithm for solving ambiguities in the NOE assignments. These ambiguities mainly arise from chemical shift degeneration which allows multiple assignments of cross peaks. Using a set of 326 protein NMR structures, statistical tables in the form of atom-pairwise volume probability distributions (VPDs) were derived. VPDs for all assignment possibilities relevant to the assignments of interproton NOEs were calculated. With these data for a given cross peak with N possible assignments Ai (i = 1,...,N) the conditional probabilities P(Ai, a/V0) can be calculated that the assignment Ai determines essentially all (a-times) of the cross peak volume V0. An assignment Ak with a probability P(Ak, a/V0) higher than 0.8 is transiently considered as unambiguously assigned. With a list of unambiguously assigned peaks a set of structures is calculated. These structures are used as input for a next cycle of iteration where a distance threshold Dmax is dynamically reduced. The program KNOWNOE was tested on NOESY spectra of a medium size protein, the cold shock protein (TmCsp) from Thermotoga maritima. The results show that a high quality structure of this protein can be obtained by automated assignment of NOESY spectra which is at least as good as the structure obtained from manual data evaluation.

Algorithms↗

The determinants of skeletal muscle force and power: their adaptability with changes in activity pattern.

A kinetic model of the cross-bridge cycle in skeletal muscle is presented with special reference to the rate limiting steps regulating the peak rate of force development (dP/dt), peak force (P0), and the maximal shortening speed (Vmax). Force production in skeletal muscle is dependent on the number of cross-bridges in the strongly bound, high-force state (AM'-ADP), and during a peak isometric contraction this state is the dominant cross-bridge form. The peak force and power output of a muscle depends upon numerous factors to include: (1) muscle and fiber size and length; (2) architecture, such as the angle and physical properties of the fiber-tendon attachment, and the fiber to muscle length ratio; (3) fiber type; (4) number of cross-bridges in parallel; (5) force per cross-bridge; (6) peak dP/dt; (7) force-velocity relationship; (8) fiber Vmax; (9) force-pCa2+ relationship: and (10) the force-frequency (action potential Hz) relationship. In this paper, we discuss these determinants of force and power output, and consider how they adapt to both muscle unloading (induced by hindlimb suspension) and programs of regular endurance exercise. Slow- and fast-twitch fibers have similar capacities to generate specific tension (kg cm-2). However, fast fibers show a considerably higher peak dP/dt, Vmax, and power output. The high Vmax of the fast-twitch fiber is likely due to the high myofibrillar ATPase activity of the fast myosin isozyme. Both hindlimb suspension and regular endurance exercise have been shown to induce fiber type specific changes in single fiber function. For example, fiber size and the peak tetanic tension of the slow oxidative (SO), fast oxidative glycolytic (FOG), and fast glycolytic (FG) fiber types were generally unaltered by endurance exercise-training. In contrast, hindlimb suspension produced cell atrophy in all fiber types and a reduced specific tension in the SO but not the FOG or FG fiber types. Both exercise-training and HS shifted the force-pCa curve to the right, and increased the Vmax of the SO fiber type. From the standpoint of work capacity or the ability to move a load, the important functional property is power output. Peak power is obtained at loads considerably below 50% of PO, and it is correlated with the percentage of fast-twitch fibers. Peak power can be increased by both dynamic and isometric programs of exercise-training.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

Measuring community competence in the Mississippi Delta: the interface between program evaluation and empowerment.

If political dynamics are included in the definition of community, health promotion programs have a greater potential to recognize that assisting people to empower their communities is as important as assisting them to improve their health. This paper reports on the evaluation methods employed for a health promotion program in a rural poor county of the Mississippi Delta that chose to define community in this way. The evaluation took an action research approach so that the methods would not contradict or interfere with the program's empowerment agenda. The methods required a close and collaborative working relationship among evaluators and local service providers, community leaders, and program staff who defined and operationalized eight dimensions of community competence, determined the units of analysis, and developed the data collection protocol. Emphasis was placed on using the data to engage the program and three communities in a dialogue on how to confront a system with the difficult issues they faced. The findings revealed that after 1 year of implementation, community competence moved from social interactions internal to communities to those more externally focused on mediating with outside institutions and officials. At the same time, measures of self-other awareness and conflict containment showed a decrease or virtual nonexistence.

Adolescent↗

Learning a single limb multijoint coordination pattern: the impact of a mechanical constraint on the coordination dynamics of learning and transfer.

The coordination dynamics of learning and transfer were studied in a single limb multijoint task requiring rhythmic elbow and wrist motions. Participants were required to learn a continuous 90 degrees relative phase pattern between the elbow and wrist such that an angle-angle plot of elbow and wrist motion produced a circle with a diameter of 80 degrees. Joint motion was restricted to elbow and wrist flexion-extension on the sagittal plane and the to-be-learned 90 degrees relative phase pattern was always practiced with the learning arm supine. Cycling frequency was controlled by a pacing metronome set at 0.75 Hz. Issues regarding effector-independent and effector-specific transfer were addressed with three transfer conditions: (1). learning arm prone (LP), (2). non-learning arm supine (NS), and (3). non-learning arm prone (NP). Four subjects learned the required relative phase (90 degrees ) and amplitude (80 degrees ) pattern with their dominant arm and four with their non-dominant arm. The experiment produced three main findings with regard to elbow-wrist control processes: First, seven of eight participants spontaneously produced a wrist-lagging coordination pattern (wrist motion lagged elbow motion) in learning to produce a continuous relative phase pattern of 90 degrees between the elbow and wrist. The wrist-lagging pattern may emerge as a result of the central nervous system exploiting the transfer of angular momentum from the elbow to the wrist as the elbow rotates up and down. The influence of interactive torque on elbow-wrist coordination represents an important mechanical constraint on the selection of intralimb coordination strategies during learning. The transfer conditions revealed that this mechanical constraint was effector-independent with regard to ipsilateral limb transfer (LP) and contralateral limb transfer (NS and NP). Second, consistent transfer of the learned relative phase pattern across ipsilateral and contralateral conditions demonstrates an effector-independent representation for this control variable. The effector-independent and effector-specific nature of joint amplitude transfer was dependent to some degree on learning arm, dominant or non-dominant, and the amount of practice, 1 day versus 5 days. Third, learning of the required 90 degrees relative phase pattern may be characterized as a phase transition leading to the formation of a stable attractor in the elbow-wrist coordination landscape. The above findings are discussed with respect to motor programming and coordination dynamic viewpoints on effector-independent and effector-specific aspects of motor equivalence.

Adult↗

Vancomycin-resistant enterococci in intensive-care hospital settings: transmission dynamics, persistence, and the impact of infection control programs.

Vancomycin-resistant enterococci (VRE) recently have emerged as a nosocomial pathogen especially in intensive-care units (ICUs) worldwide. Transmission via the hands of health-care workers is an important determinant of spread and persistence in a VRE-endemic ICU. We describe the transmission of nosocomial pathogens by using a micro-epidemiological framework based on the transmission dynamics of vector-borne diseases. By using the concept of a basic reproductive number, R0, defined as the average number of secondary cases generated by one primary case, we show quantitatively how infection control measures such as hand washing, cohorting, and antibiotic restriction affect nosocomial cross-transmission. By using detailed molecular epidemiological surveillance and compliance monitoring, we found that the estimated basic reproductive number for VRE during a study at the Cook County Hospital, Chicago, was approximately 3-4 without infection control and 0.7 when infection control measures were included. The impact of infection control was to reduce the prevalence from a predicted 79% to an observed 36%. Hand washing and staff cohorting are the most powerful control measures although their efficacy depends on the magnitude of R0. Under the circumstances tested, endemicity of VRE was stabilized despite infection control measures, by the constant introduction of colonized patients. Multiple stochastic simulations of the model revealed excellent agreement with observed pattern. In conjunction with detailed microbiological surveillance, a mathematical framework provides a precise template to describe the colonization dynamics of VRE in ICUs and impact of infection control measures. Our analyses suggest that compliance for hand washing significantly in excess of reported levels, or the cohorting of nursing staff, are needed to prevent nosocomial transmission of VRE in endemic settings.

Anti-Bacterial Agents↗

Refinement of the F-actin model against X-ray fiber diffraction data by the use of a directed mutation algorithm.

The F-actin model has been refined by a Directed Mutation Algorithm, a reiterative procedure which combines a Monte-Carlo method of selecting subdomains to be refined at each cycle with a non-linear least-squares routine to get the best fit for the particular selected domains. The G-actin crystal structure was used as a starting model. The experimental data were obtained by X-ray fiber diffraction patterns from oriented F-actin gels. After 250 cycles we were able to obtain an almost perfect fit of the calculated diffraction pattern to the experimental diffraction pattern as well as a reasonable stereochemistry including intermolecular interactions of the actin monomers with an r.m.s. shift in the C alpha-positions of 3.2 A from the crystal coordinates. The stereochemistry of the intersubunit packing was calculated by molecular dynamics using the program X-PLOR. In addition, the binding site of phalloidin, a cyclic heptapeptide from the mushroom Amanita phalloides, could be determined. Furthermore, we were able to determine differences in the structures of F-actin with and without phalloidin. The method proved itself robust and showed a high degree of convergence.

Actins↗

High-resolution solution NMR structure of the Z domain of staphylococcal protein A.

Staphylococcal protein A (SpA) is a cell-wall-bound pathogenicity factor from the bacterium Staphylococcus aureus. Because of their small size and immunoglobulin (IgG)-binding activities, domains of protein A are targets for protein engineering efforts and for the development of computational approaches for de novo protein folding. The NMR solution structure of an engineered IgG-binding domain of SpA, the Z domain (an analog of the B domain of SpA), has been determined by simulated annealing with restrained molecular dynamics on the basis of 671 conformational constraints. The Z domain contains three well-defined alpha-helices corresponding to polypeptide segments Lys7 to Leu17 (helix 1), Glu24 to Asp36 (helix 2), and Ser41 to Ala54 (helix 3). A family of ten conformers representing the solution structure of the Z domain was computed by simulated annealing of restrained molecular dynamics using the program CONGEN. The average of the root-mean-square deviations (r.m. s.d.) of the individual NMR conformers, relative to the mean coordinates, for the backbone atoms N, Calpha and C' of residues Phe5 through Ala56 is 0.69 A; the corresponding backbone r.m.s.d. for the three-helical core is 0.44 A. Helices 1, 2 and 3 are antiparallel in orientation (Omega12=-170(+/-4) degrees , Omega13=+16(+/-3) degrees , Omega23=+173(+/-7) degrees ). A comparison of backbone amide hydrogen/deuterium exchange rates in free and IgG-bound Z domains demonstrates that the amide protons of helices 1, 2 and 3 are protected from rapid exchange in both states, indicating that all three helices are also intact in the IgG-bound state. These solution NMR results differ from the previously determined X-ray structure of the similar SpA B domain in complex with the Fc fragment of a human IgG antibody, where helix 3 is not observed in the electron density map and from the solution NMR structure of the B domain, where helix 3 is observed but helix 1 is tilted by approximately 30 degrees with respect to helices 2 and 3. Hydrogen-bonded N-cap and C-cap formation is observed for all three helices of the Z domain; these capping interactions appear to be highly conserved in the five homologous domains of SpA.

Amino Acid Sequence↗

The solution structure of omega-Aga-IVB, a P-type calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta.

The 48 amino acid peptides omega-Aga-IVA and omega-Aga-IVB are the first agents known to specifically block P-type calcium channels in mammalian brain, thus complementing the existing suite of pharmacological tools used for characterizing calcium channels. These peptides provide a new set of probes for studies aimed at elucidating the structural basis underlying the subtype specificity of calcium channel antagonists. We used 288 NMR-derived constraints in a protocol combining distance geometry and molecular dynamics employing the program DGII, followed by energy minimization with Discover to derive the three-dimensional structure of omega-Aga-IVB. The toxin consists of a well-defined core region, comprising seven solvent-shielded residues and a well-defined triple-stranded beta-sheet. Four loop regions have average backbone rms deviations between 0.38 and 1.31 A, two of which are well-defined type-II beta-turns. Other structural features include disordered C- and N-termini and several conserved basic amino acids that are clustered on one face of the molecule. The reported structure suggests a possible surface for interaction with the channel. This surface contains amino acids that are identical to those of another known P-type calcium channel antagonist, omega-Aga-IVA, and is rich in basic residues that may have a role in binding to the anionic sites in the extracellular regions of the calcium channel.

Agatoxins↗

The effect of unilateral isokinetic strength training on local adipose and muscle tissue morphology, thickness, and enzymes.

One-leg exercise of 5 weeks duration in 10 healthy middleaged women resulted in a significant increment of muscle force in the exercising leg and in a less, but at some angular velocities also significant, increase in the nonexercising leg. The thickness of subcutaneous tissue measured by ultrasound and skinfold caliper decreased, while muscle thickness increased in the exercising leg only. The increased thickness of muscle tissue was associated with an increase in the relative number and relative fiber area of type II fibers in the exercising leg. The mean fiber area of type IIB fibers increased significantly as well as the activity of lactate dehydrogenase and myokinase. The decrease of thickness of subcutaneous adipose tissue was not associated with a significant decrease in fat cell size and was probably due to geometrical factors secondary to hypertrophy of the underlying muscle. It is concluded that the relationship between lean and fat components of the human thigh is significantly influenced by changes in the activity of the thigh skeletal muscles, but a local dynamic strength training program can hardly be used for local emptying of the fat depot over the exercising muscles.

Adenosine Triphosphatases↗

Short-term model of the production of construction aggregates in Taiwan based on artificial neural networks.

BACKGROUND: Taiwan's geography and limited stock of sandstone have caused sandstone resources to gradually decline to the point of exhaustion after long-term excavation. Moreover, the Taiwanese government has continuously increased the amount of land area near rivers that cannot be excavated to facilitate riverbed remediation and promote conservation of water resources. Accordingly, predicting and managing the annual production of construction aggregates in future construction projects, and dealing appropriately with some thorny problems, for instance, demand that excess supply, excessive excavation, unregulated excavation, and the consequent environmental damage, will significantly affect the efficient use of natural resources in a manner that accords with the national policy of Sustainable Development (SD). METHODS: . This study establishes an empirical model for forecasting the annual production of future construction aggregates using Artificial Neural Networks (ANN), based on 15 relevant socio-economic indicators, such as indicator of annual consumption of cement. A sensitivity analysis is then performed on these indicators. RESULTS AND DISCUSSION: This work applies ANN to estimate the annual production of construction aggregates; the estimates, the verification of the model and the sensitivity analysis are all acceptable. Furthermore, sensitivity analysis results indicate that the annual consumption of cement is the indicator that most strongly influences the production of construction aggregates, as well as whether construction waste can be recycled and steel structures can be used in buildings, helping to reduce the future production of construction aggregates in Taiwan. CONCLUSIONS: The elaborate prediction methodology presented in this study avoids some of the weaknesses or limitations of conventional linear statistics, linear programming or system dynamics. Additionally, the results not only provide a short-term prediction of the production of construction aggregates in Taiwan, but also provide a viable and flexible means of verifying quality certification of the production data of construction aggregates in the future by incorporating those relevant socio-economic indicators. RECOMMENDATIONS AND OUTLOOK: The continuity and quality of the database of relevant indicators used in this study should be closely scrutinized in order to ensure the SD means of exploiting resources.

Conservation of Natural Resources↗

Biodistribution and radiation dosimetry of [123I]ADAM in healthy human subjects: preliminary results.

[(123)I]ADAM [2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM)] has recently been shown to be a very promising imaging ligand for the detection of serotonin transporters (SERT) in human brain, because of its high specificity for SERT. [(123)I]ADAM has previously been used only for animal studies. In this work, we investigated the radiation dosimetry and biodistribution of [(123)I]ADAM based on whole-body scans in healthy human volunteers. Following the administration of 196+/-20 MBq (range 157-220 MBq) [(123)I]ADAM, serial whole-body images were performed up to 24 h. Estimates of radiation absorbed dose were calculated using the MIRDOSE 3.0 program with a dynamic bladder model. Twelve source organs were considered in estimating absorbed radiation doses for organs of the body. The highest absorbed organ doses were found to the lower large intestine wall (8.3.10(-2) mGy/MBq), kidneys (5.2.10(-2) mGy/MBq), urinary bladder wall (4.9.10(-2) mGy/MBq) and thyroid (4.3.10(-2) mGy/MBq). The effective dose was estimated to be 2.2.10(-2) mSv/MBq. The results suggest that [(123)I]ADAM is of potential value as a tracer for single-photon emission tomography imaging of serotonin receptors in humans, with acceptable dosimetry and high brain uptake.

Adult↗