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PubMed2002

Monitoring of complex industrial bioprocesses for metabolite concentrations using modern spectroscopies and machine learning: application to gibberellic acid production.

Two rapid vibrational spectroscopic approaches (diffuse reflectance-absorbance Fourier transform infrared [FT-IR] and dispersive Raman spectroscopy), and one mass spectrometric method based on in vacuo Curie-point pyrolysis (PyMS), were investigated in this study. A diverse range of unprocessed, industrial fed-batch fermentation broths containing the fungus Gibberella fujikuroi producing the natural product gibberellic acid, were analyzed directly without a priori chromatographic separation. Partial least squares regression (PLSR) and artificial neural networks (ANNs) were applied to all of the information-rich spectra obtained by each of the methods to obtain quantitative information on the gibberellic acid titer. These estimates were of good precision, and the typical root-mean-square error for predictions of concentrations in an independent test set was <10% over a very wide titer range from 0 to 4925 ppm. However, although PLSR and ANNs are very powerful techniques they are often described as "black box" methods because the information they use to construct the calibration model is largely inaccessible. Therefore, a variety of novel evolutionary computation-based methods, including genetic algorithms and genetic programming, were used to produce models that allowed the determination of those input variables that contributed most to the models formed, and to observe that these models were predominantly based on the concentration of gibberellic acid itself. This is the first time that these three modern analytical spectroscopies, in combination with advanced chemometric data analysis, have been compared for their ability to analyze a real commercial bioprocess. The results demonstrate unequivocally that all methods provide very rapid and accurate estimates of the progress of industrial fermentations, and indicate that, of the three methods studied, Raman spectroscopy is the ideal bioprocess monitoring method because it can be adapted for on-line analysis.

Algorithms↗

PubMed1994

Bridging the gap between basic and clinical electrophysiology: what can be learned from monophasic action potential recordings?

With rapid advances occurring in both basic and clinical electrophysiology, the gap between the two disciplines appears to be widening rather than narrowing. In most instances, we cannot apply the knowledge derived from cellular studies directly to clinical practice. Monophasic action potential (MAP) recording by contact electrode technique allows us to measure basic electrophysiological phenomena in the human heart and thus provides an important bridge between basic and clinical electrophysiology. MAP recordings produce the time course of cellular repolarization during cycle length changes and antiarrhythmic drug administration, lending insights into use dependency and reverse use dependency of antiarrhythmic drug effects in the clinical electrophysiology laboratory. The ability to deliver electrical stimuli at the MAP recording site further allows one to investigate drug-induced postrepolarization refractoriness. MAP recordings provide precise local activation times, important for mapping of abnormal ventricular activation, and detect areas of abnormal repolarization due to ischemia or scarring. MAP recordings are uniquely suited to detect early and delayed afterdepolarizations in the human heart, thereby helping to unravel the arrhythmia mechanisms in the long QT syndrome. By embedding the MAP electrode in a radiofrequency electrode, arrhythmogenic foci may be both detected and ablated. In many instances, MAP recordings are more accurate than ECG tracings in defining and distinguishing ventricular fibrillation and ventricular tachycardia. This can be of clinical importance during testing of the implantable cardioverter/defibrillator. An area of growing interest is stretch-activated arrhythmias. Here, MAP recordings are of particular value because no other method is available to record mechanically induced electrophysiological changes in the vigorously beating heart. It can be expected that MAP recordings will, in the future, provide this important bridge between "cell and bedside" also in atrial tachyarrhythmias, such as in atrial fibrillation and flutter.

Action Potentials↗

PubMed1989

Learning a living as medical radiation technologist.

Rapid technological change is threatening the ability of current diploma-level medical radiation technology training programs to produce professionals capable of recognizing and adapting to change. The authors argue that because an increasing number of allied medical professions in Canada and abroad are instituting university-level training programs, a degree program in radiation sciences that draws on a wider range of scientific disciplines should also be established in Canada. Such programs would graduate better-trained, more adaptable radiology professionals and help establish medical radiation technology as a true profession with all the benefits such status confers.

Curriculum↗

PubMed2001

Rapid hiv testing in urban outreach: a strategy for improving posttest counseling rates.

In 1998, 48% of persons who had HIV testing at publicly funded sites in the United States failed to return for test results and posttest counseling. Opportunities for timely HIV therapy were lost; valuable resources were wasted. This study tested the hypothesis that rapid HIV testing enables a high percentage of high-risk outreach clients to learn their serostatus. We did on-site counseling and rapid HIV testing at community-based organizations (e.g., chemical dependency programs, homeless shelters) in North Minneapolis. The project tested 735 persons. All but one (99.9%) learned their HIV serostatus. African Americans made up 79% of subjects. Rapid testing has a role to play in HIV outreach. It is useful in populations who are at high risk of HIV infection, who currently are not accessing HIV testing, and who have high failure to return rates. Future developments in rapid testing technology will make this testing option more convenient and cost-effective.

AIDS Serodiagnosis↗

PubMed2003

Enhancement of learning processes following an acute modafinil injection in mice.

Modafinil is a wakeness-promoting drug, which is effective in the treatment of narcolepsy; its effects on learning processes are however little studied. Thus, the present study was aimed at determining the effects of an acute modafinil injection on a serial reversal discrimination task performed in a T-maze in mice. Independent groups of mice varying by the level of pretest training (either 1 or 4 days of training) were used. Mice were injected each day with a gum arabic solution before each session began. On the second or the fifth day of training, a single dose of modafinil was injected before testing. Modafinil at 64 mg/kg but not at 32 mg/kg dramatically improved performance as compared to controls in subjects being trained 4 days, but not in subjects being trained 1 day. This improvement of learning was due to the more rapid emergence of a win-stay strategy in modafinil-treated subjects as compare to controls. Thus, our data show that an acute modafinil injection enhances learning processes.

Animals↗

PubMed2005

[Validation of BREV: comparison with reference battery in 173 children with learning disorders].

INTRODUCTION: The BREV battery (Battery for rapid evaluation of cognitive functions) is a tool which can be used for the rapid neuropsychological evaluation of children aged between 4 and 9 years. OBJECTIVES: After standardization (700 unaffected children) and validation by comparison with a reference battery (202 children with epilepsy), the aim of this study was further validation in 173 children with learning disorders. POPULATION AND METHODS: The study protocol included administration of the BREV, precise neuropsychological examination and evaluation of oral and written language. Statistical analysis was used to compare the findings of the BREV with those of the reference method, and the recommendations indicated by the BREV with the final diagnoses, and to define the sensitivity and the specificity of the BREV battery. RESULTS: All the correlations between BREV tests and reference tests were significant. Recommendations after the BREV were in agreement with the conclusions of the reference evaluation in 168/172 children for language, 145/173 for the psychometric evaluation. For only 4 chidren, the results of the BREV were false negative. Diagnoses corresponded in 168/173 children for oral language, in 102/110 for written language, 166/173 for praxis disorders and 157/173 for intellectual deficit. The most predictive subtests of the BREV and sensitivity and specificity of verbal and non-verbal scores were calculated. CONCLUSION: The BREV is a reliable examination, in learning disorders, to determine the most complementary investigations both in terms of language disorders and for non-verbal or global learning disabilities.

Child↗

PubMed2006

Neural cell adhesion molecule (NCAM-/-) null mice show impaired sensitization of the startle response.

The neural cell adhesion molecule (NCAM) plays important roles in development of the nervous system and in synaptic plasticity and memory formation in the adult. The present study sought to further investigate the role of NCAM in learning by testing habituation and footshock sensitization learning of the startle response (SR) in NCAM null mutant (NCAM-/-) and wildtype littermate (NCAM+/+) mice. Whereas habituation is a form of non-associative learning, footshock sensitization is induced by rapid contextual fear conditioning. Habituation was tested by repetitive presentation of acoustic and tactile startle stimuli. Although NCAM-/- mice showed differences in sensitivity in both stimulus modalities, habituation learning was intact in NCAM-/- mice, suggesting that NCAM does not play a role in the mechanisms underlying synaptic plasticity in the startle pathway. Footshock sensitization was elicited by presentation of electric footshocks between two series of acoustic stimuli. In contrast to habituation, footshock sensitization learning was attenuated in NCAM-/- mice: the acoustic SR increase after the footshocks was lower in the mutant than in wildtype mice, indicating that NCAM plays an important role in the relevant brain areas, such as amygdala and/or the hippocampus.

Acoustic Stimulation↗

PubMed2001

Perceptual learning without perception.

The brain is able to adapt rapidly and continually to the surrounding environment, becoming increasingly sensitive to important and frequently encountered stimuli. It is often claimed that this adaptive learning is highly task-specific, that is, we become more sensitive to the critical signals in the tasks we attend to. Here, we show a new type of perceptual learning, which occurs without attention, without awareness and without any task relevance. Subjects were repeatedly presented with a background motion signal so weak that its direction was not visible; the invisible motion was an irrelevant background to the central task that engaged the subject's attention. Despite being below the threshold of visibility and being irrelevant to the central task, the repetitive exposure improved performance specifically for the direction of the exposed motion when tested in a subsequent suprathreshold test. These results suggest that a frequently presented feature sensitizes the visual system merely owing to its frequency, not its relevance or salience.

Adult↗

PubMed2002

Deciding to learn: modulation of learning flights in honeybees, Apis mellifera.

Upon discovering new sources of food, honeybees and other insects perform learning flights to memorize visual landmarks that can guide their return. Learning flights are longest following initial visits to the food and subsequently decline in duration, which suggests that the investment in learning results from an active decision modulated by a bee's accumulating experience. We document various factors that influence this decision: (1). learning flights reappear when experienced bees encounter a delay in finding food at a familiar place and the durations of such "reorientation flights" increase with the length of the delay; (2). the decay in learning flight duration over visits following such reorientation flights is more rapid than following initial discovery of the food; (3). learning flight duration increases with the visual complexity of the scene surrounding the food, and when spatial relationships among landmarks are unstable; and (4). durations of learning flights at a new feeding place are influenced by the sucrose concentration in the food. Taken together, these experiments suggest that bees can adjust their learning efforts in response to changing needs for visual information and that both sources of spatial uncertainty and the quality of the food influence the value of such information.

Animals↗

PubMed1979

Operant conditioning of infant monkeys (Macaca fascicularis) for toxicity testing.

A technique has been developed that allows infant monkeys to perform on an operant schedule as soon as they are able to self-feed. Behavior is shaped in small increments through a series of operants; sensory and motor systems as well as performance on schedules using intermittent reinforcement may be tested as early as 3-4 weeks of age. This is accomplished by exposing the infant to the operant situation almost continuously, and allowing the infant to feed only by operantly responding. Infants exposed to lead post-natally differed from controls in pattern of fixed ratio responding, "activity" as measured by pattern of responding over the course of the session, and on a two-choice form discrimination reversal learning set paradigm. This technique allows rapid accumulation of large amounts of data without experimenter intervention.

Animals↗

PubMed1990

Factors related to speed of assembling blocks without boundary frames after trials with the frames.

Three frames that enclose equal areas for a rectangle, a Greek cross, and an isosceles triangle were used to study how 122 subjects learned to fill the frames rapidly with five blocks for five trials, and then the effect of requiring the shapes to be assembled for five more trials without the frames. Assembling all three shapes during each trial caused interference. Many instances occurred of a shape taking longer to be assembled on trial 6 than on trial 1. During the last five trials, the appropriate frame was provided whenever 3 minutes elapsed. Subjects with no 3-minute failures had a higher IQ than the others. Men's assembly time correlated with scores on a visual closure test; proficient men benefited in the frameless situation from their closure skill.

Adult↗

PubMed2002

A technique for open trocar placement in laparoscopic surgery using the umbilical cicatrix tube.

BACKGROUND: Increasingly the open method for placement of the initial or first trocar is replacing the conventional technique with the Veress needle. Indeed, it is preferred because it affords peritoneal access under direct vision. A number of methods have been described in the literature using a variety of approaches and different instruments. METHODS: We describe a method of open trocar placement in the supra- or subumbilical region that follows a stepwise procedure and employs specific instruments sequentially, while utilizing the umbilical cicatrix pillar or tube. RESULTS: This technique has been done in 525 cases with no complications or port site hernias. CONCLUSION: This is a simple technique that is safe and easy to learn. It can be performed rapidly and is a reliable method for the insertion of the first port under vision.

Catheterization↗

PubMed2005

Formative assessment of use of behavioral data in HIV prevention: Texas.

A formative assessment was conducted with Texas HIV prevention community planning group (CPG) members, prevention provider staff, and supervisors of those staff to better understand how to enhance their use of epidemiologic and behavioral data in the selection and prioritization of prevention interventions. Semi-structured interviews, mail surveys, and content analysis of funding proposals were used to determine the current use of these data, their perceived value, and the most trusted sources for data. CPG members, prevention provider staff, and supervisors valued information from their peers and networking most, and made more use of socially available information than they did research or systematically collected assessment data. CPG members wanted more local data and data on specific sub-populations of interest. Prevention providers viewed the utility of behavioral data as limited, and were primarily concerned with the pragmatic aspects of fielding interventions; however, this group also expressed an interest in rapid community assessment methods and learning more about new and effective prevention interventions. These results led to the development of training and technical assistance materials.

Adult↗

PubMed1982

The present and future of human factors.

In view of the problems facing human factors specialists, how do they feel about the present status of their profession and its future prospects? A small number of highly qualified practitioners were asked their opinions about various questions which have been discussed in two previous articles in this series. In a 1979 survey they agreed that designers rarely solicit human engineering assistance and resist human engineering inputs; that the behavioural research reported in the literature is of relatively little value in system development work; that government does not monitor human engineering in system development very effectively. In a survey performed for this article, specialists were generally optimistic about the future of their discipline but concerned about government funding and job support under the Reagan administration; felt that engineering and public acceptance of human factors is increasing slowly; were ambivalent about any significant improvement in methodology; and considered that the scope of human factors work would expand in the future. The need for human factors should increase in the future and the future looks reasonably promising if specialists learn to deal with a rapidly changing technological environment.

Journal Article↗

PubMed1994

Receptor mediation of the stimulus properties of cholecystokinin.

Recently, Melton, Kopman, and Riley (20) reported the rapid acquisition of drug discrimination learning using the sulfated form of cholecystokinin (CCK) within the conditioned taste aversion baseline of drug discrimination learning. The present study was designed to explore the receptor mediation of the stimulus properties of CCK within this procedure. Every fourth day, experimental subjects were given CCK-saccharin-LiCl pairings, and on the intervening recovery days, saccharin alone. Once discriminative control was established, doses of the CCK receptor antagonists devazepide (CCK-type A receptor subtype) and L-365,260 (CCK-type B receptor subtype) were administered in combination with the training dose of CCK. Unlike L-365,260 (1-1000 micrograms/kg), devazepide (1 microgram/kg) blocked the CCK stimulus, suggesting that within this design CCK's stimulus properties are mediated by the CCK-type A receptor subtype.

Animals↗

PubMedDate not supplied

Adolescent addiction. Assessment and identification.

Adolescents who are addicted to drugs present unique assessment and diagnostic problems. The primary drugs used by adolescents are alcohol, marijuana, and cocaine, respectively. The adolescent who uses drugs in a regular and frequent manner is affected more rapidly than is the adult who uses in the same way and for the same length of time. The social and emotional skills usually acquired during this period of rapid growth often are not learned when the adolescent is abusing drugs, and this results in psychosocial stunting of development. Drugs and alcohol have been implicated in teenage traffic accidents, school drop out rates, promiscuity, crime, and suicide. Assessing adolescent drug use and potential addiction is not difficult once good history and examination techniques are acquired. This article presents techniques for assessing and identifying addicted adolescents.

Adolescent↗

PubMed2006

Regulation of neuronal PKA signaling through AKAP targeting dynamics.

Central to organization of signaling pathways are scaffolding, anchoring and adaptor proteins that mediate localized assembly of multi-protein complexes containing receptors, second messenger-generating enzymes, kinases, phosphatases, and substrates. At the postsynaptic density (PSD) of excitatory synapses, AMPA (AMPAR) and NMDA (NMDAR) glutamate receptors are linked to signaling proteins, the actin cytoskeleton, and synaptic adhesion molecules on dendritic spines through a network of scaffolding proteins that may play important roles regulating synaptic structure and receptor functions in synaptic plasticity underlying learning and memory. AMPARs are rapidly recruited to dendritic spines through NMDAR activation during induction of long-term potentiation (LTP) through pathways that also increase the size and F-actin content of spines. Phosphorylation of AMPAR-GluR1 subunits by the cAMP-dependent protein kinase (PKA) helps stabilize AMPARs recruited during LTP. In contrast, induction of long-term depression (LTD) leads to rapid calcineurin-protein phosphatase 2B (CaN) mediated dephosphorylation of PKA-phosphorylated GluR1 receptors, endocytic removal of AMPAR from synapses, and a reduction in spine size. However, mechanisms for coordinately regulating AMPAR localization, phosphorylation, and synaptic structure by PKA and CaN are not well understood. A kinase-anchoring protein (AKAP) 79/150 is a PKA- and CaN-anchoring protein that is linked to NMDARs and AMPARs through PSD-95 and SAP97 membrane-associated guanylate kinase (MAGUK) scaffolds. Importantly, disruption of PKA-anchoring in neurons and functional analysis of GluR1-MAGUK-AKAP79 complexes in heterologous cells suggests that AKAP79/150-anchored PKA and CaN may regulate AMPARs in LTD. In the work presented at the "First International Meeting on Anchored cAMP Signaling Pathways" (Berlin-Buch, Germany, October 15-16, 2005), we demonstrate that AKAP79/150 is targeted to dendritic spines by an N-terminal basic region that binds phosphatidylinositol-4,5-bisphosphate (PIP(2)), F-actin, and actin-linked cadherin adhesion molecules. Thus, anchoring of PKA and CaN as well as physical linkage of the AKAP to both cadherin-cytoskeletal and MAGUK-receptor complexes could play roles in coordinating changes in synaptic structure and receptor signaling functions underlying plasticity. Importantly, we provide evidence showing that NMDAR-CaN signaling pathways implicated in AMPAR regulation during LTD lead to a disruption of AKAP79/150 interactions with actin, MAGUKs, and cadherins and lead to a loss of the AKAP and anchored PKA from postsynapses. Our studies thus far indicate that this AKAP79/150 translocation depends on activation of CaN, F-actin reorganization, and possibly Ca(2+)-CaM binding to the N-terminal basic regions. Importantly, this tranlocation of the AKAP79/150-PKA complex from spines may shift the balance of PKA kinase and CaN/PP1 phosphatase activity at the postsynapse in favor of the phosphatases. This loss of PKA could then promote actions of CaN and PP1 during induction of LTD including maintaining AMPAR dephosphorylation, promoting AMPAR endocytosis, and preventing AMPAR recycling. Overall, these findings challenge the accepted notion that AKAPs are static anchors that position signaling proteins near fixed target substrates and instead suggest that AKAPs can function in more dynamic manners to regulate local signaling events.

A Kinase Anchor Proteins↗

PubMed2006

Evolving medical knowledge: moving toward efficiently answering questions and keeping current.

The information needs of clinicians are many and varied; however, these information needs remain largely unmet. This likely diminishes the quality of patient care. Although it is important that physicians be proficient in critically evaluating the medical literature, it is more important that they become proficient in the "applied science of information management." Clinicians must learn the techniques and skills to find, evaluate, and use relevant and valid information both in the care of patients and in their careers of lifelong learning. Clinicians need sources for rapid retrieval of valid information at the point of care.

Education, Medical, Continuing↗