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A growth kinetic model of Kluyveromyces marxianus cultures on cheese whey as substrate.

This work presents a multi-route, non-structured kinetic model for determination of microbial growth and substrate consumption in an experimental batch bioreactor in which beta-galactosidase is produced by Kluyveromyces marxianus growing on cheese whey. The main metabolic routes for lactose, and oxygen consumption, cell growth, and ethanol production are derived based on experimental data. When these individual rates are combined into a single growth rate, by rewriting the model equations, the model re-interpretation has a complexity similar to that of the usual variations of the Monod kinetic model, available in the literature. Furthermore, the proposed model is in good agreement with the experimental data for different growth temperatures, being acceptable for dynamic simulations, processes optimization, and implementations of model-based control technologies.

Bioreactors↗

Fidelity of implementation in Project Towards No Drug Abuse (TND): a comparison of classroom teachers and program specialists.

This paper presents the results of an effectiveness trial of Project Towards No Drug Abuse [TND], in which we compared program delivery by regular classroom teachers and program specialists within the same high schools. Within 18 schools that were randomly assigned to the program or control conditions, health classrooms were assigned to program delivery by teachers or (outside) specialists. Classroom sessions were observed by pairs of observers to assess three domains of implementation fidelity: adherence, classroom process, and perceived student acceptance of the program. Pre- and immediate posttest survey data were collected from 2331 students. Of the four composite indexes of implementation fidelity that were examined, only one (quality of delivery) showed a difference between specialists and teachers, with marginally higher ratings of specialists (p < .10). Both teachers and program specialists achieved effects on three of the five immediate outcome measures, including program-specific knowledge, addiction concern, and social self-control. Students' posttest ratings of the program overall and the quality of program delivery failed to reveal differences between the teacher- and specialist-led classrooms. These results suggest that motivated, trained classroom teachers can implement evidence-based prevention programs with fidelity and achieve immediate effects.

Adult↗

Analysis of standing up and sitting down in humans: definitions and normative data presentation.

A formal definition of human standing up and sitting down movements based on sagittal plane goniometric and force plate data from 20 normal subjects is presented. This definition is comparable to the established gait cycle diagram, and consists of defined characteristic events and relative time intervals between them. The characteristic events are selected primarily on changes in ground reaction forces. The terminology proposed may be valuable for introducing more formalized and standardized reporting of both qualitative and quantitative studies in both normals and in patients. This presentation is directed toward the process of defining generally acceptable standards for human standing up and sitting down movements.

Abdomen↗

Cross-cultural adaptation of health measures. European Group for Health Management and Quality of Life Assessment.

There is increasing interest throughout Europe in measuring health needs in the general population and in the 'quality of life' of patients. This has led to a demand for questionnaires capable of measuring health status in a reliable and valid manner. Most existing measures have, however, been standardised only in the U.S.A. and, to a lesser extent, in the U.K. The issue of translation and retesting of questionnaires prepared in the English language for use in other countries has received surprisingly little attention. This paper describes some of the technical, linguistic and conceptual issues raised by translation and the processes involved in producing acceptable country-specific versions of the Nottingham Health Profile according to a systematic method.

Cross-Cultural Comparison↗

Optical design with the aid of a genetic algorithm.

Natural evolution is widely accepted as being the process underlying the design and optimization of the sensory functions of biological organisms. Using a genetic algorithm, this process is extended to the automatic optimization and design of optical systems, e.g. as used in astronomical telescopes. The results of this feasibility study indicate that various types of aberrations can be corrected quickly and simultaneously, even on small computers.

Algorithms↗

The impact of computer systems in a medical environment.

The acceptance and proliferation of computer technology in health care has not been as rapid as many expected. Research in this area suggests that several factors are related to computer acceptance including social network processes, attitudes toward computers, and personality characteristics. Potential implications for the field of magnetic resonance imaging are discussed.

Attitude to Computers↗

The COP9 signalosome (CSN): an evolutionary conserved proteolysis regulator in eukaryotic development.

The COP9 signalosome (CSN) is a multiprotein complex of the ubiquitin-proteasome pathway. CSN is typically composed of eight subunits, each of which is related to one of the eight subunits that form the lid of the 26S proteasome regulatory particle. CSN was first identified in Arabidopsis where it is required for the repression of photomorphogenic seedling development in the dark. CSN or CSN-related complexes have by now been reported from most eukaryotic model organisms and CSN has been implicated in a vast array of biological processes. It is widely accepted that CSN directly interacts with cullin-containing E3 ubiquitin ligases, and that CSN is required for their proper function. The requirement of CSN for proper E3 function may at least in part be explained by the observation that CSN subunit 5 (CSN5) is the isopeptidase that deconjugates the essential ubiquitin-like Nedd8 modification from the E3 cullin subunit. In addition to its interaction with E3s, CSN may also regulate proteolysis by its association with protein kinases and deubiquitylating enzymes. This review provides a summary of the role of CSN in regulating protein degradation and in eukaryotic development.

Animals↗

Acceptance-based treatment for persons with complex, long standing chronic pain: a preliminary analysis of treatment outcome in comparison to a waiting phase.

The concept of acceptance is receiving increased attention as an alternate approach to the suffering that is often associated with persistent and disabling pain. This approach differs from established treatments in that it does not principally focus on reducing pain, but on reducing the distressing and disabling influences of pain as they concern important areas in patients' lives. The present analyses represent a preliminary evaluation of an acceptance-based approach to chronic pain within an interdisciplinary treatment program. One hundred and eight patients with complex chronic pain conditions completed treatment and provided data for the current study. Treatment was conducted in a 3- or 4-week residential or hospital-based format. It included a number of exposure-based, experiential, and other behavior change methods focused on increasing (a) engagement in daily activity regardless of pain and (b) willingness to have pain present without responding to it. Significant improvements in emotional, social, and physical functioning, and healthcare use were demonstrated following treatment. The majority of improvements continued at 3-months post-treatment. Improvements in most outcomes during treatment were correlated with increases in acceptance, supporting the proposed process of treatment.

Activities of Daily Living↗

Functional explanation and the function of explanation.

Teleological explanations (TEs) account for the existence or properties of an entity in terms of a function: we have hearts because they pump blood, and telephones for communication. While many teleological explanations seem appropriate, others are clearly not warranted--for example, that rain exists for plants to grow. Five experiments explore the theoretical commitments that underlie teleological explanations. With the analysis of [Wright, L. (1976). Teleological Explanations. Berkeley, CA: University of California Press] from philosophy as a point of departure, we examine in Experiment 1 whether teleological explanations are interpreted causally, and confirm that TEs are only accepted when the function invoked in the explanation played a causal role in bringing about what is being explained. However, we also find that playing a causal role is not sufficient for all participants to accept TEs. Experiment 2 shows that this is not because participants fail to appreciate the causal structure of the scenarios used as stimuli. In Experiments 3-5 we show that the additional requirement for TE acceptance is that the process by which the function played a causal role must be general in the sense of conforming to a predictable pattern. These findings motivate a proposal, Explanation for Export, which suggests that a psychological function of explanation is to highlight information likely to subserve future prediction and intervention. We relate our proposal to normative accounts of explanation from philosophy of science, as well as to claims from psychology and artificial intelligence.

Adult↗

Pathways of neurodegeneration and experimental models of basal ganglia disorders: downstream effects of mitochondrial inhibition.

The basal ganglia circuit plays a key role in the regulation of voluntary movements as well as in behavioural control and cognitive functions. The main pathogenic role of mitochondrial dysfunctions is now accepted in the neurodegenerative process and the mitochondria have been successfully used as subcellular targets to obtain relevant experimental models of basal ganglia neurodegenerative disorders. Mitochondrial toxins act through an inhibition of the respiratory chain complexes. These toxins, by uncoupling cellular respiration, shift the cell into a state of oxidative stress and trigger several bidirectional links with the excitotoxic process. Moreover, the in vitro inhibition of the respiratory chain complexes alters the electrophysiological properties of the neurons. The downstream effects triggered by mitochondrial complexes inhibition provide a model integrating genetic and environmental pathogenic factors to explain the selective neuronal vulnerability.

Animals↗

Macromolecular MRI contrast agents for imaging tumor angiogenesis.

Angiogenesis has long been accepted as a vital process in the growth and metastasis of tumors. As a result it is the target of several novel anti-cancer medications. Consequently, there is an urgent clinical need to develop accurate, non-invasive imaging techniques to improve the characterization of tumor angiogenesis and the monitoring of the response to anti-angiogenic therapy. Macromolecular MR contrast media (MMCM) offer this diagnostic potential by preferentially exploiting the inherent hyperpermeable nature of new tumor vessels compared with normal vessels. Over the last 10-15 years many classes of MMCM have been developed. When evaluated with dynamic contrast enhanced (DCE) MRI, a number of MMCM have demonstrated in vivo imaging properties that correlate with ex vivo histological features of angiogenesis. The enhancement patterns with some MMCM have been reported to correlate with tumor grade, as well as show response to anti-angiogenic and anti-vascular drugs. Future applications of MMCM include targeted angiogenesis imaging and drug delivery of anti-cancer 'payloads'. Herein we discuss the best known MMCMs along with their advantages and disadvantages.

Contrast Media↗

A plastid in the making: evidence for a second primary endosymbiosis.

One of the major steps in the evolution of life was the origin of photosynthesis in nucleated cells underpinning the evolution of plants. It is well accepted that this evolutionary process was initiated when a photosynthetic bacterium (a cyanobacterium) was taken up by a colorless host cell, probably more than a billion years ago, and transformed into a photosynthetic organelle (a plastid) during a process known as primary endosymbiosis. Here, we use sequence comparisons and phylogenetic analyses of the prokaryotic rDNA operon to show that the thecate, filose amoeba Paulinella chromatophora Lauterborn obtained its photosynthetic organelles by a similar but more recent process, which involved a different cyanobacterium, indicating that the evolution of photosynthetic organelles from cyanobacteria was not a unique event, as is commonly believed, but may be an ongoing process.

Amoeba↗

Birth of piglets by in vitro fertilization of zona-free porcine oocytes.

The present experiments were conducted to optimize in vitro fertilization conditions for zona pellucida-free (ZP-free) oocytes and their subsequent development. The results demonstrated that: (1) maximal fertilization efficiency was achieved at 200 spermatozoa per ZP-free oocyte. At this sperm dose, there were no significant differences in penetration rates and polyspermy rates from controls (zona-intact oocytes with 1000 spermatozoa/oocyte), indicating that ZPs of in vitro matured pig oocytes failed to block polyspermy during in vitro fertilization. (2) In vitro development of zygotes from ZP-free oocytes showed that there was no difference in cleavage rates. The blastocyst rate was slightly lower in the ZP-free group than the control. However, there was no difference in cell number per blastocyst between the control and the ZP-free group. (3) Examination of acrosome status by a specific fluorescein isothiocyanate-conjugated peanut agglutinin (FITC-PNA) staining procedure revealed that frozen-thawed pig spermatozoa could undergo acrosome reaction and penetrate oocytes without induction by ZP. These data suggested that there are alternative mechanistic pathways for acrosome reaction induction during the fertilization process than the widely accepted sperm-zona receptor models. Finally, the viability of ZP-free derived embryos was demonstrated by full-term development and the delivery of healthy piglets following embryo transfer. In conclusion, the present experiments showed for the first time in farm animals, that normal embryos could be produced by in vitro fertilization of ZP-free oocytes in optimized conditions and that they could develop normally to full-term.

Acrosome Reaction↗

The ribosome-recycling step: consensus or controversy?

Ribosome recycling, the last step in translation, is now accepted as an essential process for prokaryotes. In 2005, three laboratories showed that ribosome-recycling factor (RRF) and elongation factor G (EF-G) cause dissociation of ribosomes into subunits, solving the long-standing problem of how this essential step of translation occurs. However, there remains ongoing controversy regarding the other actions of RRF and EF-G during ribosome recycling. We propose that the available data are consistent with the notion that RRF and EF-G not only split ribosomes into subunits but also participate directly in the release of deacylated tRNA and mRNA for the next round of translation.

Biological Transport↗

Holistic processing unites face parts across time.

When complementary halves of different familiar faces are combined into a new face, there is interference in the identification of either half. This "composite face effect" has been taken as strong evidence that faces are processed holistically. Here, we demonstrate that this effect can persist when the two parts of a face are separated by up to 80 ms of visual noise, showing that the parts of a face interact not only spatially but also temporally. We suggest that the processing underlying robust identification accepts an accumulation of evidence over time.

Adolescent↗

Motility of colon cancer cells: modulation by CD44 isoform expression.

The invasion of cancer cells at primary tumor sites and their migration during metastatic spread require the expression of cell adhesion and motility proteins. Whether accelerated cell motility is necessary in these two processes is not universally accepted. In this study we took advantage that CD44, a cell adhesion protein, has different metastatic potentials depending on its splicing isoforms to examine how they affect cell motility. We established stable transfectants of standard and variant isoforms of CD44 in SW620 cells, a human colon carcinoma cell line that does not express CD44. The morphology of the cells varied according to the CD44 isoform expressed, but actin filament distribution remained unchanged. Using the wound assay in a two-dimensional in vitro cell motility system, we found that the expression of standard CD44 increases cell motility, whereas CD44 isoforms containing an exon sequence associated with metastatic dissemination has a slowing effect. Cell proliferation was also decreased by the expression of variant CD44 isoforms. Overall, colon cancer cells expressing variant CD44 isoforms had slower cell motility, possibly due to alterations in their cell adhesion properties. In conclusion, this study suggests that, contrary to common models, the metastatic phenotype is associated with a slow rate of cell migration when tested in vitro.

Actins↗

Quantitative risk assessment: state-of-the-art for carcinogenesis.

A critical evaluation of the use of statistical models in carcinogenic risk assessment is made with emphasis on the strengths and weaknesses of current practice. The objective is to bring together information from the fields of toxicology and statistics to develop a sound scientific basis for making risk decisions. It is emphasized that risk assessment is a complex, multifaceted process that is not easily quantified and, at present, must be based on qualitative as well as quantitative information. It is evident that dose-response modeling of tumor incidence data from animal studies is of limited value in estimating human risk associated with low-dose chemical exposures. The models take into account only one part of the complex process and have no accepted basis in biology. The key decision points, qualitative factors, and quantitative considerations are identified and discussed and a risk assessment framework that incorporates these inputs is presented. A model that incorporates the tumorigenic dose-response information as well as the qualitative and quantitative biological factors that affect the estimate of risk is proposed. It is concluded that much work needs to be done before a completely quantitative approach to risk assessment is to be useful; in particular pharmacokinetic modeling should be pursued more aggressively.

Animals↗

Training, management, and credentialing for CRRT in the ICU.

Continuous renal replacement therapy (CRRT) in the intensive care unit (ICU) requires a dedicated training and educational process that includes both theoretical and practical approaches. Important goals for this process include achieving an acceptable circuit life without patient complications and providing a high percentage of staff with bedside expertise. Lectures or didactic sessions must link into bedside instruction and simulations or mock patient/circuit setup. An annual seminar may be useful for all clinicians to share and gain knowledge. Managers require a system of staff review to ensure expertise levels are maintained. Policy development, quality assurance, and complication monitoring systems provide useful information for managers and educators in this field. Credentialing may be useful to confirm the goals of CRRT, but it requires further development of practice standards before adoption.

Credentialing↗