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The systematic study of the sensory and learning processes of infants is a rather recent science; indeed, infants far surpass what we "knew" about their capacity for learning a few decades ago. Emotion and learning are closely intertwined, because behaviors that elicit positive emotional response are repeated and learned. Understanding these processes can optimize care of newborns by both professionals and parents.
The effect of negative air ions (NAI) inhalation by rats on energy reactions of mitochondria in homogenates of liver and brain was studied. The influence of NAI was investigated under activation of animals by administration of physiological dose of adrenaline. Adrenaline administration induced hyperactivation of the rate of phosphorylating oxidation of succinic acid in liver and brain mitochondria which was accompanied by oxalacetate inhibition of succinate dehydrogenase (SDH) as well as excessive Ca2+ accumulation in liver mitochondria. These changes connected with a decrease of coefficient of phosphorylation efficiency ADP/O and uncoupler stimulation of respiration evidenced decrease of energy control of respiration in mitochondria. NAI inhalation diminished the rate of hyperactivated respiration and abolished excessive Ca2+ accumulation. These changes together with ADP/O coefficient and DNP stimulation increase evidence improvement of energy control of respiration which provide more moderate function of the respiratory chain under activation by adrenaline. Animals were excited by adrenaline administration. This effect was abolished by NAI inhalation, animals relaxed, some fell asleep. The data evidence sensitivity of mitochondrial processes in internal organs to inhalation of NAI and show participation of mitochondria in realization of physiological effects of NAI.
PURPOSE: The design of an appropriate set of multiple fixed fields to achieve a steep dose gradient at the tumor edge, with minimal normal tissue exposure, is a very difficult problem, since a virtually infinite number of possible beam orientations exists. In practice we have selected beams in an iterative and often time-consuming process. This work proposes an optimization method, based on geometric and dose elements, to effectively arrive at a set of beam orientations. METHODS AND MATERIALS: Beams are selected by minimizing a goal function including an angle function (beam separation for steep dose gradient at target edge) and a length function (related to normal tissue dose volume histogram). The relative importance of these two factors may be adjusted depending on the clinic situation. The model is flexible and can include case specific practical anatomic and physical considerations. RESULTS: In extremely simple situations, the goal function yields results consistent with well-known analytical solutions. When applied to more complex clinical situations, it provides clinically reasonable solutions similar to those empirically developed by the clinician. The optimization process takes approximately 25 min on a UNIX workstation. CONCLUSION: The optimization scheme provides a practical means for rapidly designing multiple field coplanar or noncoplanar treatments. It overcomes limitations in human three-dimensional visualization such as trying to visualize beam directions and keeping track of the hinge angle between beams while accounting for anatomic/machine constraints. In practice, it has been used as a starting point for physicians to make modifications, based on their clinical judgment.
Laue data reduction has now reached a level of sophistication that allows nearly automated processing to be performed. The software described enables complete reduction of the data with essentially no user intervention, making Laue processing almost as straightforward as monochromatic data processing. Interactive work is limited to the indexing of only one Laue pattern. More importantly, it is shown that the data quality is substantially enhanced when soft-limited predictions are used. Further improvement obtained by taking advantage of the structure-factor amplitudes from a known closely related structure is described. To determine the most suitable type of insertion device to be used for time-resolved Laue crystallography, the technique described was applied to Laue data sets collected from photoactive yellow protein under identical conditions but with three different insertion devices: a wiggler, a broad-bandpass undulator and a single-line undulator. Although the optimal choice may ultimately be dictated by sample parameters (such as mosaic spread) and by the type of experiment (repeatable or non-repeatable reactions), the results here show that the use of single-line undulators will generally yield by far the best compromise between data quality, acquisition time and radiation damage.
Process development and optimization studies were performed in order to improve the purification process of (rhIFN-gamma). The objective was to generate material with higher purity and quantity. An in-process control screening was developed to obtain the optimal condition for column chromatographic purification by measuring LPS, nucleic acids, rhIFN- gamma, monomer and its covalent dimers. A new resin screening method was applied to select optimal resin for each of the chromatographic columns. The resulting process used Butyl and Q-Sepharose, refolding and SP-Sepharose for purification of IFN-gamma. Effects of different process conditions such as cell lysis, removal of impurity and oxygen concentration were evaluated. Removal of impurities was evaluated by washing of inclusion bodies with 1% Triton X-100 and 3M urea and different chromatography steps. The results reveal that Triton removed about 43% of the LPS but urea had no effect on removal of nucleic acids and LPS. Further analysis show that removal of impurities by column chromatography decreases aggregation and increases the process yield. Oxygen concentration was identified as parameter that could have a significant impact on covalent dimers formation, as an unacceptable pharmaceutical form of rhIFN-gamma. On the basis of small-scale studies, optimum operating conditions were chosen and the purification process was successfully scaled-up to a pilot scale process with step yield and product quality that were better than previous reports.
This paper presents a novel method for iterative batch-to-batch dynamic optimization of bioprocesses. The relationship between process performance and control inputs is established by means of hybrid grey-box models combining parametric and nonparametric structures. The bioreactor dynamics are defined by material balance equations, whereas the cell population subsystem is represented by an adjustable mixture of nonparametric and parametric models. Thus optimizations are possible without detailed mechanistic knowledge concerning the biological system. A clustering technique is used to supervise the reliability of the nonparametric subsystem during the optimization. Whenever the nonparametric outputs are unreliable, the objective function is penalized. The technique was evaluated with three simulation case studies. The overall results suggest that the convergence to the optimal process performance may be achieved after a small number of batches. The model unreliability risk constraint along with sampling scheduling are crucial to minimize the experimental effort required to attain a given process performance. In general terms, it may be concluded that the proposed method broadens the application of the hybrid parametric/nonparametric modeling technique to "newer" processes with higher potential for optimization.
Atherogenesis and inflammation are dependent on macrophage function. Signalling pathways are involved in the modulation of the classical low density lipopotein (LDL)-receptor and scavenger receptors activities, which are both expressed by macrophages. This study has evaluated the role of activation of the protein kinase A and C pathways in human macrophages on the metabolism of lipid carried by native, acetylated and oxidised LDL. We found that [3H]oleate incorporation into cholesteryl ester and triacylglycerol is increased by an analogue of cAMP, but strongly inhibited by treatment with phorbol ester (PMA) (100 nM, 6 h) in the presence of acLDL and oxLDL and, to a lesser extent, nLDL. The mechanisms underlying the effects of the phorbol ester were investigated further. The protein kinase C inhibitors, calphostin C and herbimycin A, prevented the PMA-mediated inhibition of cholesterol esterification. PMA also reduced [14C]acetate incorporation into newly synthesised lipids especially in the presence of nLDL, and reduced the uptake of cholesterol carried by modified LDL. Furthermore, the effects of PMA were not modified by inhibition of proteases activities, ruling out the hypothesis that CD163, a scavenger receptor which is shed by the cell surface in the presence of phorbol, is involved in the phorbol-induced reduction of cholesterol accumulation in macrophages in response to LDL. We conclude that binding of modified LDL to macrophages induces an appropriate pattern of scavenger receptor phosphorylation which, in turn, determines the optimal receptor internalisation process. PMA activates PKC pathways and prevents the optimal ligand-induced phosphorylation of the receptors, compromising the processes of degradation of modified LDL. The data also suggest that this mechanism may be related to the decreased uptake by activated macrophages of lipid carried by modified lipoproteins during the early phases of inflammation (284).
Dynamic programming to solve the Markov decision process problem of optimal insemination and replacement decisions was adapted to address large dairy herd management decision problems in the US. Expected net present values of cow states (151,200) were used to determine the optimal policy. States were specified by class of parity (n = 12), production level (n = 15), month of calving (n = 12), month of lactation (n = 16), and days open (n = 7). Methodology optimized decisions based on net present value of an individual cow and all replacements over a 20-yr decision horizon. Length of decision horizon was chosen to ensure that optimal policies were determined for an infinite planning horizon. Optimization took 286 s of central processing unit time. The final probability transition matrix was determined, in part, by the optimal policy. It was estimated iteratively to determine post-optimization steady state herd structure, milk production, replacement, feed inputs and costs, and resulting cash flow on a calendar month and annual basis if optimal policies were implemented. Implementation of the model included seasonal effects on lactation curve shapes, estrus detection rates, pregnancy rates, milk prices, replacement costs, cull prices, and genetic progress. Other inputs included calf values, values of dietary TDN and CP per kilogram, and discount rate. Stochastic elements included conception (and, thus, subsequent freshening), cow milk production level within herd, and survival. Validation of optimized solutions was by separate simulation model, which implemented policies on a simulated herd and also described herd dynamics during transition to optimized structure.
Although fed-batch suspension culture of animal cells continues to be of industrial importance for the large scale production of pharmaceutical products, existing control concepts are still insufficient. Changes in cell metabolism during cultivation and between similar cultivations, the complexity of the cell metabolism, and the lack of on-line state variables restrict the transfer of available control strategies established in bioprocess engineering. A process control strategy designed to achieve optimized process control must account for all these difficulties and fit sophisticated requirements toward adaptability and flexibility. The combination of a fed-batch process and an Open-Loop-Feedback-Optimal (OLFO) control provides a new approach for cell culture process control that couples an efficient cultivation concept to a capable process control strategy. The application of an adaptive, model-based OLFO controller to a hybridoma cultivation and experimental results are presented.
Optimal image quality is an ideal in nuclear medicine that is not always realized, being subject to a variety of conditions that can act, either singly or in combination, to undermine its accomplishment. These conditions include potential defects and limitations in both the hardware and software used for the acquisition and reconstruction of nuclear medicine images. Factors relating to individual patients can contribute to these obstacles, including limitations in mobility and compliance. Importantly, suboptimal or erroneous technique is a common source of poor imaging results, with loss of diagnostic efficacy. Appropriate test selection and careful attention to patient preparation and procedural details are essential elements in avoiding image flaws and artifacts in nuclear medicine.
OBJECTIVE: To optimize the preparation process and to set up the quality standard of Ephedra sinica Dispensing Granules. METHODS: Nine experiments were carried out by L9 (3(4)) orthogonal design. Ephedra sinica Dispensing Granules was identified by TLC and the content of ephedrine was determined by HPLC. RESULTS: The optimal extraction process was as follows: the water that 10 times of Ephedra sinica, was decocted 3 times and each time was sustained for 1.5 hours. The linear relationship of ephedrine hydrochloride was at the range of 0.0081 - 0.1377 microg (r = 0.999 9). The average recovery was 100.25% ( RSD = 2.24%, n = 6). CONCLUSION: The extraction process is scientific. The method is available with a good reproducibility and can control the quality of Ephedra sinica Dispensing Granules.
We investigate the number N of molecules needed to perform independent diffusion in order to achieve bonding of a single molecule to a specific site in time t(0). For a certain range of values of t(0), an increase from N to kN molecules (k>1) results in the decrease of search time from t(0) to t(0)/k. In this regime, increasing the number of molecules is an effective way of speeding up the search process. However when N> or =N0 (optimal number of N) the reduction of time from t(0) to t(0)/k can be achieved only by an exponentially large increase in the number of molecules [from N to N exp(ck) for some c>0].
We present a procedure for the optical characterization of thin-film stacks from spectrophotometric data. The procedure overcomes the intrinsic limitations arising in the numerical determination of many parameters from reflectance or transmittance spectra measurements. The key point is to use all the information available from the manufacturing process in a single global optimization process. The method is illustrated by a case study of solgel applications.
The plasma-based surface modification of polymer materials with desirable bulk properties is a useful way to obtain polymers with tailor-made surface properties. This is necessary because the surface properties of most engineering polymers in use today are less then optimum for many applications. New functionalities such as biocompatibility, adhesion, special functional groups as well as lubricative, friction and wear-and-tear properties are demanded. By optimization of the process parameters during a low pressure plasma treatment, most of these requirements can be fulfilled. A specific functionalization with, e.g., carboxyl, amino, epoxy or hydroxyl groups as well as the generation of ultra thin layers with those functionalities is possible. The most challenging problem is not only to find parameters which do not lead to a fragmentation of the monomeric structure, but moreover the adhesion of the thin films to the substrates must overcome a stability test without delamination. To optimize plasma processes, with their great variety of parameters influencing the obtained surface properties, several surface analytical techniques are indispensable. XPS, AES as well as AFM are helpful tools to characterize the modified sample surfaces and consequently optimize the set of parameters for the glow discharge treatment. With XPS the retention of the monomer structure can be controlled. AES depth profiling clarifies the elemental composition of gradient layers, necessary for a good adhesion of scratch-resistant coatings. AFM visualizes the surface morphology which is important for, e.g., the friction properties of plasma-coated substrates.
In the first part of the review, recent developments in medical imaging technology are described. Developments in transducer materials and matching, leading to improvements in band-width and sensitivity are discussed. Improvements in dynamic range due to increased transducer sensitivity, lower electronic noise levels and more efficient filtering are then considered. The benefits of the application of digital signal processing (DSP) techniques to radiofrequency (RF) echo signals are described, including more precise filtering and beam forming, synthetic aperture and parallel receive beam forming. Finally, the current situation in regard to 1.5 D arrays, 3 D scanning, ultrasound computed tomography (UCT), harmonic imaging with contrast agents and elastography are discussed. In the second part, some predictions for future developments are made. These will be possible largely due to the power of DSP. Parallel transmissions will make more efficient use of time, allowing greater spatial and temporal resolution, and greater accuracy in Doppler imaging. Adaptive transmission tailoring will be used, where the pulse characteristics to each part of the image field are independently optimized, as will adaptive receive processing in which echo sequences from each part of the image are independently and optimally processed. An important potential development will be automatic feature recognition, making possible accurate compound scanning with high spatial resolution, and quantitative information about the spatial distribution of acoustic speed. Compound scanning will provide more complete visualization of all structures and, particularly when incorporated into intravascular probes, should greatly aid the investigation of arterial plaque morphology. Feature recognition will also make it possible to have UCT systems (array based in future) which require less than 360 degrees access. Harmonic imaging without contrast agents, based simply on the inherent non-linearity of sound propagation in tissue, will become common. 2 D phased array transducer will permit symmetric beam focusing and scanning throughout a solid cone, greatly facilitating the development of 3 D scanning applications. Large 2 D arrays would have the potential to produce a five-fold increase in spatial resolution of a limited volume of tissue, or to measure the variation of backscatter with angle, as an aid to tissue characterization. Finally, ultrasound will be increasingly used to measure the elastic and dynamic properties of local regions of tissue.
In March, 2001 The World Health Organization (WHO) convened an Expert Consultation to recommend to WHO an optimal duration of exclusive breastfeeding. WHO formulated the specific questions to be addressed, selected the membership for the meeting, prepared background documents, and provided the venue for the meeting. After the meeting WHO formally accepted the recommendations and began to implement them. The Consultation recommended that WHO change its recommendation on exclusive breastfeeding from four-to-six months to a recommendation to promote exclusive breastfeeding for six months. This recommendation was contingent upon WHO also accepting and implementing other recommendations to deal with possible detrimental side effects, and to support mothers who did not exclusively breastfeed for six months. The amount of scientific evidence available was more than is often available for policy decisions in health, but much less than desirable to address issues of generalizability across and within populations. The evidence for the contingent recommendations was also less than desirable and raises a number of important research questions that now need to be addressed.
The process of producing magnetic resonance (MR) volume measurements can be divided into considerations of acquisition and postprocessing of the MR data. With careful attention to both of these, precise and reproducible measurements can be achieved. A statistical description of hippocampal measurements in normal volunteers must be available for comparison if volumetrics are employed either for clinical or research purposes. A wide range in "normal" hippocampal volume is present in the studies of normal young adults that have been reported to date. This variability is most probably due to interinstitutional differences in hippocampal boundary criteria, and in the software employed for counting pixels in a defined region of interest (ROI). Because the numeric output from the volume measurement procedure is highly technique-dependent, the statistical description of "normal" should be determined or calibrated at each institution wishing to use these techniques.
Recovery of recombinant proteins from endogenous, host molecules can be an experimentally intensive and time-consuming task. Often the time to analyze material during development of recovery procedures is the rate-limiting step. Nowadays, modern techniques and equipment are being specifically engineered to make this effort much more efficient. We present a case study to illustrate how a new, automation tool, designed for easy, systematic methods development, can be used for very rapid process and analytical optimization. This tool uses robotics to integrate process development with rapid LC-based analysis requiring no user intervention. The methods and procedures described can be generalized to any recombinant protein recovery campaign.