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PubMed1993

Concepts of optimality and efficiency in biology and medicine from the viewpoint of philosophy of science.

If everything happens strictly according to the natural laws, which meet extremum principles, in what way can the possibility for life be characterised, so that the optimization processes of evolution can take place? Is it legitimate to "enlarge" the natural laws by certain laws of conservation? The question then arises of which are the new conservation quantities that are introduced by life itself? The concept of genidentity, which must not be confused with the biological concept of genes, is introduced and used to characterise the interface between animate and inanimate systems by the principle of conservation of genidentity. It thus becomes clear that animate systems can differ in the way and in how reliably they achieve their goal of self-preservation. The abundance of possibilities to be or not to be able to reach this goal offers the necessary scope in which the notion of a postulated assumed optimization in the theory of evolution is conceivable. The conservation principle of genidentical systems creates the possibility of evolutionary optimization by ranking these systems. An optimal lifespan of an individual genidentical system refers to the conservation principle of genidentical systems on a second supra-individual level (species). The optimization of the growth of a species needs the conservation of a genidentical system on a third level (symbiotic systems). The ranking of genidentical systems onto ever higher levels--so that the higher conservation principles always impose restrictions on the ones below--would come to an end when the minimization of raw materials and energy consumption limits all possible and available resources. Since the spectrum extending between opposite goals lies within the range of possible means of optimization, supposedly evolutionary goals of optimization are always attributed to nature by the observer.

Biological Evolution↗

PubMed1995

Processing of visual motion direction in the fronto-parallel plane in the stationary or moving observer.

To examine the effect of concurrent self-motion on the perception of the direction of object-motion, random-dot kinematograms were employed in which the strength of the directional signal was manipulated by varying the percentage of coherently moving pixels. The subject's task was to indicate the motion direction of briefly presented displays while undergoing whole body rotations with angular accelerations of 0, 5, 15, or 45 degrees/s2. The perception of the direction of visual motion in the horizontal plane was impaired only when visual and vestibular motion directions were incongruous. The impairment increases with both increasing angular acceleration and decreasing percentage of coherently moving pixels. For object-motion in the vertical plane, an impairment was found for both congruous and incongruous combination of visual and vestibular stimulation, although not as pronounced for the latter (i.e., visual upward, vestibular downward stimulation, and vice versa). These results are discussed in terms of postnatal development and neurophysiological optimization processes resulting from intersensory 'updating' through every-day experience of object-motion during self-motion.

Acceleration↗

PubMed2003

Development of an automated extraction procedure for detection of human papillomavirus DNA in liquid based cytology samples.

Liquid based cytology samples are being used increasingly to improve cervical screening and have the advantage that residual cell suspension is available for other tests such as human papillomavirus (HPV) detection. However, as the transport medium is optimised for downstream cytology, problems can be experienced during extraction of nucleic acid. This study aimed to develop a robust protocol for automated extraction of HPV DNA from cervical, liquid based cytology samples using a high throughput robotic system. Considerable modification of existing clinical extraction protocols for swab specimens, together with optimisation of required sample input volume was required to reduce sample blockage during the extraction to acceptable levels. The blockage rate and optimal processing volume was assessed by extracting a fixed volume (1/4) of re-suspended material from the centrifuged pellets of 10, 5 and 1 ml aliquots of 200 specimens. Analysis revealed 17.5% blockage with specimens originating from 10 ml aliquots; 3% with 5 ml and no blockage with 1 ml aliquots of the same samples. A 3% blockage level is acceptable for an automatic well clearance procedure to be followed. HPV testing of the extracts by real-time PCR showed a 1.5% loss of sensitivity in extracts originating from 1 ml aliquots as compared with 5 ml aliquots with a consequent loss of detectable HPV genotypes after reverse hybridisation. In short, 5 ml of liquid based cytology specimen is recommended for nucleic acid extraction, to allow optimal detection of HPV types in clinical samples while retaining maximum efficiency of the robotic extraction procedure.

DNA, Viral↗

PubMed1992

Deficiency of acylpeptide hydrolase in small-cell lung carcinoma cell lines.

During protein biosynthesis, processing of the N terminus of many proteins may occur through acetylation and deacetylation. The enzyme acylpeptide hydrolase is likely involved in deacetylation of nascent peptide chains or of bioactive peptides. The related enzyme, acylase, hydrolyzes the acetyl amino acid product of the acylpeptide hydrolase reaction to acetate and a free amino acid. There is a reciprocal relationship between the substrates for these enzymes (i.e., substrates for one enzyme are competitive inhibitors for the other). In several cultured cell lines, including normal and malignant cells, the ratio of acylpeptide hydrolase to acylase enzyme activities appears to be coordinated and characteristic for a given cell type. Thus, in normal cultured lung cells, hamster ovary cells, hepatoma cells, and lymphocyte cells, nearly equal amounts of these enzymes are expressed, conducive to optimal processing of acetylated N-terminal residues. Four lines of erythroleukemic cell lines were found to express nearly twice as much acylase as acylpeptide hydrolase activity. In the Ehrlich ascites tumor cell line, where 80% of the proteins have been reported to remain acetylated at their N terminus, acylpeptide hydrolase is hardly expressed but acylase activity is not reduced. The 3p21 region of human chromosome 3, which contains the DNF15S2 locus that encodes acylpeptide hydrolase (Jones et al., Proc Natl Acad Sci USA 1991;88:2194), undergoes deletion in some carcinoma cells; the gene that encodes for the acylase is also present on region 3p of the same chromosome. We found that both acylpeptide hydrolase and acylase activities are practically absent in six small-cell lung carcinoma cell lines tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidohydrolases↗

PubMed1993

Multiple coding and the evolutionary properties of RNA secondary structure.

This article evaluates evolutionary properties of the transition from RNA primary sequence to RNA secondary structure. It focuses on the restrictions that the conservation of a protein code in an RNA sequence puts on its potential to evolve towards a specific secondary structure. Restricting the mutations to those that do not affect the coding for a protein restricts both the accessibility and the connectivity of the sequence space. The accessibility is restricted because only certain point mutations are allowed. The connectivity is restricted because no insertions and deletions are allowed. Simulating an evolutionary search process for a specific secondary structure shows that (i) the reduction of allowable point mutations allows for adaptation to some large-scale topology, but strongly reduces the possibility of small-scale adaptations, (ii) the abolition of insertions and deletions has very little effect on the results of the search process. During the evolutionary search process for a secondary structure with a specific topology and a high frequency of base-pairing the quasispecies moves into a subspace in which the similarity between secondary structures of neighboring sequences is relatively high. Increased similarity between second structures of neighboring sequences is also found in the Rev responsive element (RRE) in the lentiviruses Caprine arthritis-encephalitis virus and Visna virus. In these viruses a biased nucleotide frequency in the RRE region suggests that selection for the RRE RNA secondary structure affects the amino acid sequence of the env gene. Our results show a variation in the ruggedness of fitness landscapes which are based on a high degree of epistatic interactions. Fitness landscapes play an essential role, not only in biotic evolution, but also in all kinds of optimization processes (Hill Climbing, Simulated Annealing, Genetic Algorithms, etc). Variation in their ruggedness should therefore be taken into account in the analysis of these processes.

Amino Acid Sequence↗

PubMed1991

Observations on maximum entropy processing of MR images.

A maximum entropy (MAXENT) criteria for MR image processing optimizations has previously shown poor performance, but this note observes that there are two entirely different kinds of "data transmission" applications which appear to have been intermixed. In the two cases, "image entropy" actually refers to different kinds of data variables. The previous literature formulations are for transfer of data in which pixel-locations are the transmitted variable, and these pixels may be neither uniform nor constant. The second application concerns the MRI data set for display. Its data variables are image pixel-values of magnetization intensity, and the data transfer mode has the sense of visual display. When MAXENT criteria are modified to address an array of pixel-value intensities, and use a pixel-value information entropy rather than pixel-locations entropy, then successful data processing results. Restoring display visualization from highly nonuniform surface coils for lumbar spine scans are demonstrated, as an example of MAXENT usefulness.

Image Processing, Computer-Assisted↗

PubMed1979

[Nutritional optimization of thermal processing of canned food].

The model developed by Barreiro, Salas and Herrera (7) for the prediction of nutrient losses during the thermal processing of conduction heated foods was used in this work to optimize the thermal processing, maximizing nutrient retention in processes with equivalent sterilization values. The processes were stimulated in a digital computer (taking pea purée canned in cans 307 x 409 as the product analyzed). Aall of the processes had equivalent sterilization values with respect to Clostridium botulinum. The thiamine retention associated with each process was calculated by the model of Barreiro, Salas and Herrera (7). The maximum fraction of thiamine retained was of 0.688 for a process at 114.2 degrees C (237.5 degrees F) for 95 minutes. Also, the possibility of the existence of a can with optimum dimensions for maximum thiamine retention, with the same sterilization values, was studied. It was found that this optimum, with the same does not exist; on the contrary, the retention was at a minimum when the diameter approaches infinite and the height zero, and viceversa. For this reason, from the nutrient retention point of view, it is better to process the product in flat or slender cans for a given sterilization value.

Clostridium botulinum↗

PubMed2002

Scaling-up of a lactose wet granulation process in Mi-Pro high shear mixers.

The high shear wet granulation upscaling possibilities of a Pro-C-epT Mi-Pro 250 ml with a batch size of 40 g were investigated by down-scaling an alpha-lactose monohydrate wet granulation process from a Collette Gral 10 (8 l batch size) to a Pro-C-epT Mi-Pro with different bowl volumes of 5 l, and 1900, 900 and 250 ml. The wet granulation process was optimised in the Gral 10, next an octagonal design was build around the central point. Two process parameters, the impeller tip speed and the water content, were varied at three levels, which resulted in a two-factor three-level experimental design. alpha-Lactose monohydrate 200 M was granulated using a polyvinylpyrollidone K 30 (2.5% on dry material) binder solution. The granules were dried at 25 degrees C for 24 h, sieved and characterised. The granules were compressed to tablets. In all mixer volumes the used impeller tip speed range did not influence the granule or tablet properties. In all bowl volumes the influence of water concentration on actual yield, particle size distribution and granule friability was similar. All batch sizes resulted in tablets of similar quality. For the selected formulation the lab scale Mi-Pro high shear mixers with different bowl volumes could be used to determine the optimal process parameters and to scale up to the Collette Gral 10 pilot scale.

Lactose↗

PubMed2002

A photoacoustic technique for depth-resolved in situ monitoring of biofilms.

Biofilms occur in natural and engineered water systems. Biofouling in technical processes lowers the water quality and increases the frictional resistance in tubes. In wastewater treatment plants, biofilms are used for removal of organic an inorganic pollutants. For improvement of antifouling strategies and for process optimization in wastewater treatments plants, an analytical technique for online monitoring of biofilms is needed. In this article, a new setup for in situ monitoring of biofilms by photoacoustic spectroscopy is presented. To produce a biofilm, a mixture of microorganisms was grown in a nutrient solution inside a tube reactor. The content of the tube reactor was pumped through a flow channel, and biofilms were generated at the inner surfaces. Three photoacoustic sensor heads were integrated at different positions into the base plate of the flow channel. By photoacoustic spectroscopy, growth, thickness, and detachment of biofilms can be monitored on-line and nondestructively. Experiments presented in this article showed that the flow conditions influence the structure and thickness of biofilms. By changing the pH value, electrostatic interactions inside the biofilm matrix were influenced, and the subsequent detachment processes were observed online. The interaction of iron(III) oxide particles with biofilms led to particle adsorption on the outer and inner surfaces of the biofilm. Afterwards, biofilm flocs were sloughed off from the base biofilm.

Acoustics↗

PubMedDate not supplied

A triage system for processing fine needle aspiration cytology specimens.

Fine needle aspiration (FNA) cytology is increasingly used in the operating room, in radiology suites and in physicians' offices. A major cause of nondiagnostic FNA specimens is poor preparation techniques. To avoid this problem, we have developed a triage system for handling and preparing FNA specimens. (1) For aspirations performed without a cytotechnologist present, the aspirate is rinsed into 50% ethanol; Cytospin slides are then prepared and stained by the Papanicolaou method. Clinicians are disposed toward this indirect method since no special slide preparation techniques are necessary. The results are equal to those of direct smear preparations, and material so prepared may also be used for immunocytochemistry. (2) When a cytotechnologist is present, both direct and indirect preparations are made. (3) When an immediate interpretation is desired, to ensure adequacy and/or to make a diagnosis, alcohol-fixed direct smears are stained with a modified toluidine blue-eosin stain and read by the cytopathologist. This offers the advantage of a quick diagnosis, which may be made in less than 90 seconds, but with nuclear detail equal to that of the Papanicolaou stain and with good background staining. In summary, our three-tiered approach offers optimal processing for aspirates collected in various settings in our institution.

Biopsy, Needle↗

PubMed1991

Developing criteria for ordering common ancillary services.

This article describes the process utilized to develop criteria for appropriately ordering five ancillary services frequently performed in hospitals: 1) arterial blood gases, 2) electrocardiograms (ECGs), 3) serum electrolytes, 4) chest x-rays, and 5) complete blood counts (CBCs). The development of each set of criteria involved an initial consultant, a panel of six additional regional expert consultants, and three national reviewers. Each criteria set was developed through a process involving seven steps: 1) an initial working draft, 2) revisions at an initial meeting of the regional experts, 3) revisions at a second meeting of the regional experts, 4) written comments from the regional experts, 5) written comments from national reviewers, 6) additional written comments from regional experts, and 7) application of the criteria to cases in a community hospital. The change in item content was measured between steps and agreement with individual items was measured at steps 2, 3, and 4. The results indicate that appreciable change in content occurred with each step except step 4. Agreement started fairly high and was over 90% by step 4. The discussion considers the utility of each developmental step, factors affecting the utility of the criteria, the extent to which the results can be generalized, and the need for more research to identify optimal processes for the development of criteria to evaluate quality of care.

Ancillary Services, Hospital↗

PubMed2001

Quantitative microbiological risk assessment.

The production of safe food is being increasingly based on the use of risk analysis, and this process is now in use to establish national and international food safety objectives. It is also being used more frequently to guarantee that safety objectives are met and that such guarantees are achieved in a cost-effective manner. One part of the overall risk analysis procedure-risk assessment-is the scientific process in which the hazards and risk factors are identified, and the risk estimate or risk profile is determined. Risk assessment is an especially important tool for governments when food safety objectives have to be developed in the case of 'new' contaminants in known products or known contaminants causing trouble in 'new' products. Risk assessment is also an important approach for food companies (i) during product development, (ii) during (hygienic) process optimalization, and (iii) as an extension (validation) of the more qualitative HACCP-plan. This paper discusses these two different types of risk assessment, and uses probability distribution functions to assess the risks posed by Escherichia coli O157:H7 in each case. Such approaches are essential elements of risk management, as they draw on all available information to derive accurate and realistic estimations of the risk posed. The paper also discusses the potential of scenario-analysis in simulating the impact of different or modified risk factors during the consideration of new or improved control measures.

Animals↗

PubMed1992

Geostatistical and morphological methods applied to three-dimensional microscopy.

Three-dimensional (3-D) images of osteocyte lacunae were examined on a confocal microscope. Both geostatistical and morphological processing techniques were used to improve and to analyse them. By a geostastical approach, this study aims at improving 3-D confocal images before any further image processing. Optimized linear filters, which take account of the second-order statistics and the 3-D structure of the data, allow for the removal of imperfections such as noise and/or blur due to the axial convolution, and interpolate voxels on a face-centred cubic grid from an initial cubic grid. An application of this technique to 3-D biological images is demonstrated. In a second step, a 3-D binary image is digitized and cleaned with 3-D morphological filters. The standard 3-D measurements cannot be applied in this case, since all osteocytes cut the border of the field. For this reason a 3-D Boolean model has been adjusted, from which it is possible to derive all useful information on the repartition and the morphology of the osteocytes.

Humans↗

PubMed1996

Infective endocarditis: ten-year review of medical and surgical therapy.

BACKGROUND: Infective endocarditis is a complex disease process. Optimal outcome often requires both medical and surgical expertise. The need for and timing of surgical intervention is controversial and continues to evolve in parallel to advancements in diagnosis and treatment. Our experience with the treatment of infective endocarditis is reviewed herein. METHODS: A retrospective review was compiled of 140 consecutive patients who fulfilled the modified von Reyn criteria for the diagnosis of endocarditis between January 1982 and April 1992. RESULTS: Patient characteristics, symptoms, and risk factors are described. Follow-up averaged 3.5 +/- 0.8 years and totaled 491 patient-years. New York Heart Association functional class at presentation had a significant influence on survival (p < 0.0001). Long-term survival was significantly greater (p = 0.036) in patients treated medically/surgically than those treated with medical therapy alone (75% versus 54% at 5 years). Medical treatment of aortic and prosthetic endocarditis was associated with higher mortality (58% and 67%, respectively) when compared with combined medical/surgical treatment (28% and 38%, respectively). Among the survivors, New York Heart Association class at follow-up was better (p < 0.0001) in the medical/surgical group (1.05 +/- 0.04) versus the medical treatment group (1.70 +/- 0.14). CONCLUSIONS: Combined medical/surgical treatment for infective endocarditis is associated with improved survival. Patients with aortic or prosthetic endocarditis are identified as subgroups that benefit most from surgical intervention. Valvular dysfunction incited by the infective process is an important factor that should be weighed carefully in the therapeutic decision.

Adolescent↗

PubMed1996

Implications of 3-dimensional target shape and motion in aperture design.

To determine the shape of a radiation beam aperture a margin is typically applied to the clinical target volume (CTV) to yield the planning target volume (PTV), and the aperture is then determined from the projection of the PTV onto the aperture plane. This margin accounts for setup variability and organ motion originating from respiration or other physiologic processes. The use of either a uniform margin, or alternatively one which takes into account only the expected magnitude and direction of target motion, fails to account for the three-dimensional nature of the target; such a method neglects the volumetric effect of target shape on the fractional target volume irradiated when the target shifts partially out of the aperture. A mathematical framework is developed to analyze and illustrate the consequences of irradiating an irregular target shape in the presence of target motion. The effect of target shape on volume coverage is demonstrated for selected cases involving conventional BEV aperture design techniques. The volumetric implications of target shape are considered from two complementary points of view. The first involves transformation into a "displacement space," which isolates the volumetric effect of the shape of the target allowing it to be studied independently of the probability distribution of target motion. The second point of view combines the effects of the 3D target shape and the probability distribution of motion in a manner independent of beam direction to yield a 3D "target distribution." The two points of view represent distinct starting points for computation of the expected value of fractional target volume coverage in the presence of target motion. In certain cases it may be beneficial to (1) employ "target distributions" for the target and normal tissues in place of the conventional static PTV and, (2) include the aperture shape, on equal footing with parameters such as beam weights and energies, into a quantitative optimization process explicitly accounting for uncertainties in the position of the target volume and critical structures.

Equipment Design↗

PubMed1998

Influence of physical exercise on aging rats. III. Life-long exercise modifies the aging changes of the mechanical properties of limb muscle tendons.

We have previously shown that long-term regular physical exercise has a systemic influence on the rat by slowing the aging of its connective tissues, measured as thermal stability and biomechanical properties of tail tendons. This paper analyses whether the properties of limb muscle tendons are influenced not only by the aging process and the systemic effects of exercise but also from direct mechanical stimuli from long-term physical exercise. Male Sprague-Dawley rats were trained in a treadmill from the age of 5 to 23 months. The effects of training on muscle tendons were analyzed with respect to biomechanical properties. Also, the viscoelastic activation energies for interactions between collagen and the proteoglycan gel as well as between collagen fibrils were measured. Finally the asymptotes from the creep curves were calculated in order to estimate the magnitude of the viscoelastic creep. The effects of aging were analyzed with respect to the same parameters by comparing the group of 23-month-old sedentary rats with a 5-month-old baseline group. The biomechanical parameters did not change significantly with physical exercise. Neither did the activation energies change, but the asymptotes of the creep curves decreased, showing that there was less viscoelastic creep. Aging rendered the tendons significantly stronger and stiffer, increased the energy-absorbing capacity and decreased the strain values. The activation energies did not change with aging, but the high creep curve asymptote for the flexor tendons decreased. We conclude that aging rendered both types of tendons stiffer, and decreased their strain values at breaking point. Aging also increased the stress value, the energy absorption and the dry weight for the flexor tendon. Further, while physical exercise has a systemic delaying effect on age changes in connective tissues, in tendons subjected to substantial mechanical loads this effect as measured with biomechanical methods is counteracted by the optimization process elicited by the same physical exercise.

Aging↗

PubMed1996

Structure optimization of an artificial neural filter detecting membrane-spanning amino acid sequences.

An artificial neural network has been developed for the recognition and prediction of transmembrane regions in the amino acid sequences of human integral membrane proteins. It provides an additional prediction method besides the common hydrophobicity analysis by statistical means. Membrane/nonmembrane transition regions are predicted with 92% accuracy in both training and independent test data. The method used for the development of the neural filter is the algorithm of structure evolution. It subjects both the architecture and parameters of the system to a systematical optimization process and carries out local search in the respective structure and parameter spaces. The training technique of incomplete induction as part of the structure evolution provides for a comparatively general solution of the problem that is described by input-output relations only. Seven physiochemical side-chain properties were used to encode the amino acid sequences. It was found that geometric parameters like side-chain volume, bulkiness, or surface area are of minor importance. The properties polarity, refractivity, and hydrophobicity, however, turned out to support feature extraction. It is concluded that membrane transition regions in proteins are encoded in sequences as a characteristic feature based on the respective side-chain properties. The method of structure evolution is described in detail for this particular application and suggestions for further development of amino acid sequence filters are made.

Algorithms↗

PubMed1999

The Design of Leadlike Combinatorial Libraries.

The optimization of low-potency leads into drugs is often accompanied by an increase in molecular weight (M(r)) and lipophilicity, as a consequence of affinity enhancement. Hits with affinity at µM levels discovered by screening leadlike libraries allow scope for this optimization process, as shown schematically by the distributions of M(r) for a leadlike library (1), oral drugs (2), and a typical combinatorial chemistry library (3). y=percentage with a particular molecular weight.

Journal Article↗