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At least 505 records · Page 28Linked to original sources

PubMed2001

Lessons from the past: biotic recoveries from mass extinctions.

Although mass extinctions probably account for the disappearance of less than 5% of all extinct species, the evolutionary opportunities they have created have had a disproportionate effect on the history of life. Theoretical considerations and simulations have suggested that the empty niches created by a mass extinction should refill rapidly after extinction ameliorates. Under logistic models, this biotic rebound should be exponential, slowing as the environmental carrying capacity is approached. Empirical studies reveal a more complex dynamic, including positive feedback and an exponential growth phase during recoveries. Far from a model of refilling ecospace, mass extinctions appear to cause a collapse of ecospace, which must be rebuilt during recovery. Other generalities include the absence of a clear correlation between the magnitude of extinction and the pace of recovery or the resulting ecological and evolutionary disruption the presence of a survival interval, with few originations, immediately after an extinction and preceding the recovery phase, and the presence of many lineages that persist through an extinction event only to disappear during the subsequent recovery. Several recoveries include numerous missing lineages, groups that are found before the extinction, then latter in the recovery, but are missing during the initial survival-recovery phase. The limited biogeographic studies of recoveries suggest considerable variability between regions.

Animals↗

PubMed1981

On the attribution and additivity of binding energies.

It can be useful to describe the Gibbs free energy changes for the binding to a protein of a molecule, A-B, and of its component parts, A and B, in terms of the "intrinsic binding energies" of A and B, DeltaG(A) (i) and DeltaG(B) (i), and a "connection Gibbs energy," DeltaG(s) that is derived largely from changes in translational and rotational entropy. This empirical approach avoids the difficult or insoluble problem of interpreting observed DeltaH and TDeltaS values for aqueous solutions. The DeltaG(i) and DeltaG(s) terms can be large for binding to enzymes and other proteins.

Journal Article↗

PubMed1998

Redesign of choline acetyltransferase specificity by protein engineering.

Since the development of site-directed mutagenesis techniques over 15 years ago (Zoller, M. J., and Smith, M. (1982) Nucleic Acids Res. 10, 6487-6500), it has been a goal of protein engineering to utilize the procedure to redesign existing enzyme structures to produce proteins with altered or novel catalytic properties. To date, however, the more successful achievements have relied exclusively on the availability of three-dimensional protein structure maps to direct the redesign strategies. Presently, such maps are unavailable for choline acetyltransferase and carnitine acetyltransferase, enzymes that catalyze the reversible transfer of an acetyl group from acetyl-CoA to choline and L-carnitine, respectively. A more empirical approach, based on cross-referencing substrate structure comparisons with protein alignment data, was used to redesign choline acetyltransferase to accommodate L-carnitine as an acceptor of the acetyl group. A mutant choline acetyltransferase that incorporates four amino acid substitutions from wild type, shows a substantial increase in catalytic efficiency (kcat/Km) toward L-carnitine (1,620-fold) and shifts the catalytic discrimination between choline and L-carnitine by >390,000 in favor of the latter substrate. These dramatic alterations in catalytic function demonstrate that significant success in protein redesign can be achieved in the absence of three-dimensional protein structure data.

Amino Acid Sequence↗

PubMed1999

Generation of the amyloid-beta peptide N terminus in Saccharomyces cerevisiae expressing human Alzheimer's amyloid-beta precursor protein.

The Alzheimer's amyloid-beta precursor protein (betaAPP) is a type 1 membrane-spanning protein from which the Alzheimer's disease amyloid-beta peptide (Abeta) is proteolytically derived. To date, attempts to identify the enzymes responsible for Abeta generation have failed. Here we report the accumulation of Abeta-immunoreactive peptides in yeast expressing human betaAPP. Characterization of these peptides by metabolic labeling, immunoprecipitation with Abeta-specific antibodies, and N-terminal radiosequencing indicates that these peptides include the Abeta peptide at their N termini. The Abeta-like peptides generated in yeast were recovered predominantly as 8- and 12-14-kDa species. A 4-kDa species was recovered either when a protease-deficient strain was used to prevent breakdown or when the 8- and 12-14-kDa species were treated with disaggregating agents. The likely existence in yeast of enzymes generating the Abeta N terminus indicates that the molecular identification of yeast beta-secretase-like enzymes may be accomplished using genetic screens or empirical approaches based upon the sequenced genome of Saccharomyces cerevisiae.

Alzheimer Disease↗

PubMed1995

Vaccines against leishmaniasis.

Unlike some other parasites, Leishmania can be grown in cell-free media with ease. This simple cultivation and the use of killed parasites as skin-test antigens (leishmanin) for diagnosis in humans during the past several decades have prompted scientists to try using the killed parasites, with or without adjuvant, as vaccines or for immunotherapy. In addition, different recombinant molecules, either parasite fractions or genetically engineered organisms (i.e. Leishmania made avirulent by removing specific genes, or bacteria carrying and expressing leishmanial genes), are being investigated as potential future vaccines against leishmaniasis. The 'first-generation' vaccines, composed of killed parasites with or without adjuvant, have been derived using an empirical approach. The 'second-generation' vaccines have been genetically constructed, using a more rational approach. At present, the first-generation vaccines are at various stages of Phase I (safety), II (reactivity) or III (efficacy) trials in humans. Results are expected in 1-2 years. The second-generation vaccines are, however, only in a preclinical state and are not expected to reach clinical trials for at least 3 years. The Special Programme for Research and Training in Tropical Diseases (TDR) is actively involved in most clinical trials of the first-generation vaccines and supports many of the second-generation candidates. In the present article, the advantages and disadvantages of each approach to vaccine development are discussed and the progress being made is briefly reviewed.

Animals↗

PubMed2001

An exploratory study on the career anchors of educators in Singapore.

In this exploratory study, the authors adopted an empirical approach to determine the various primary career anchors possessed by Singapore educators, the impact of the degree of congruency between teaching and the career anchors on intrinsic and extrinsic satisfaction, and turnover intentions. A number of hypotheses were supported and provided the 1st step in understanding this group of important individuals who nuture the future generation of human capital for the workplace.

Adult↗

PubMed2000

Temporal patterning of competitive emotions: a critical review.

An interactional model of stress that integrates current research on competitive affects and emphasizes the temporal dimensions of the stress process is forwarded. The literature reveals that the study of athletes' affective responses to competition has been narrowly focused on pre-competitive anxiety. Equivocal findings on temporal patterning of competitive anxiety suggest that a fundamental change in the empirical approach is needed because the current conceptualization of anxiety and other complex emotions is imprecise. The analysis of secondary emotions as patterns of discrete basic emotions, as suggested by differential emotions theorists, is proposed for consideration in future research. In this view, competitive anxiety is considered as a set of patterns of emotions rather than a unitary affect. The adoption of this approach could result in better operationalization of competitive anxiety as well as other secondary performance-related emotions. We propose that research on competitive affects should follow two parallel lines. The first should focus on the description of complex emotional states that reflect the idiosyncratic emotional experience and vocabulary of the athlete. The second should examine the sets of basic emotions experienced throughout competition, and focus on individual differences and factors determining those differences. The integration of the two approaches could lead to a better understanding of whether, how and why individuals differ in the interpretation of specific secondary emotions and their effect on performance. Moreover, it would permit the analysis of intra-individual variations in labelling secondary emotions with respect to different competitive contexts and temporal aspects.

Anxiety↗

PubMed2003

Estimation of polishing and leaching behaviour of antifouling paints using mathematical modelling: a literature review.

The development of chemically active antifouling paints has traditionally been based on an empirical approach. Optimisation and evaluation of novel and existing products are frequently conducted by means of, for example, systematic paint rotary tests in the laboratory or at sea sites. In this review, the usefulness of combining rotary experiments with the development of detailed mathematical models of paint behaviour will be discussed with reference to the relevant literature. Mathematical models can generally be used in the design of suitable release systems for various active components such as proteins or biocides, as well as for the estimation of release rates from different compositions of paints under various seawater conditions. Insoluble matrix, soluble matrix and self-polishing paints will be considered. Simulations from recent publications that show the effects of dynamic changes in seawater on paint behaviour will be presented. Examples of potential uses of paint models for accelerated polishing and leaching tests and screening of novel paint components will also be discussed. Directions of future modelling work are suggested.

Materials Testing↗

PubMed1999

Assessment of the protection efficiency and comfort of personal protective equipment in real conditions of use.

The lack of scientific and technical knowledge in certain complex fields, together with schedule constraints, have lead to adopt in EN standards insufficiently validated tests, relying sometimes on an empirical approach. Thus, even personal protective equipment (PPE) with positive results in tests required by the standards can nevertheless prove to be unsatisfactory when used at work. Several research projects have already been carried out on equipment, fall arresting systems, protective clothing, and gloves by several health and safety institutes in Europe. The results would suggest practical solutions to improve the representativity of several European Committee for Standardization (CEN) test methods and to focus more on informing and training workers on the manner of wearing PPE, in particular respiratory protective equipment or hearing protectors.

Ergonomics↗

PubMedDate not supplied

Memory for items and memory for relations in the procedural/declarative memory framework.

A major area of research in memory and amnesia concerns the item specificity of implicit memory. In this paper we address several issues about the nature of implicit memory phenomena and about what constitutes an "item", using the procedural/declarative memory theory to guide us. We consider the nature of memory for items and of memory for relations among items, within the context of the procedural/declarative framework, providing us with the foundation necessary to analyse the basis for item-specific implicit memory phenomena. We review recent work from our laboratories demonstrating the fundamentally relational and flexible nature of declarative memory representation, in both humans and animals, and the essential role of the hippocampal system in relational memory processing. We show, further, that the memory representations supporting implicit memory phenomena are inflexible and nonrelational, and are tied to specific processing modules. Finally, we introduce empirical approaches that blur the distinction between skill learning and repetition priming, and show computational modelling results that demonstrate how these two implicit memory phenomena can be mediated by a single incremental learning mechanism, in accord with the claims of the procedural-declarative theory. Taken together, these various analyses of memory for items and memory for relations help to illuminate the nature of the functional deficit in amnesia and the memory systems of the brain.

Amnesia↗

PubMed2006

From hawks and doves to self-consistent games of territorial behavior.

Explaining the "prior-residence effect" (automatic owner status of individuals who arrived first in an area) was one of the very first applications of game theory in animal behavior. These models, however, predict paradoxical solutions where intruders always win, with no satisfactory explanation for the absence of such cases in nature. We propose a solution based on new developments in evolutionary game theory. A self-consistent model with feedbacks between individual behavior and population dynamics produces qualitatively different frequency-dependent selection on intruders (floaters) than on territory owners. Starting with an ancestral population with no respect for ownership, the most likely evolutionary end point is complete or partial respect. Conventional rules of conflict resolution thus can rely on "uncorrelated asymmetries" without differences in resource-holding power or territory value, although they will be strengthened by such differences. We also review the empirical literature on animal contests, testing whether asymmetries in resource-holding power are required to explain the observations. Despite much empirical effort, results remain inconclusive, because experiments are often unable to distinguish between the motivation of individuals to fight and the behavioral outcome of a contest. To help arrive at conclusive answers, we suggest a standardized empirical approach to quantify prior-residence effects.

Animals↗

PubMed1997

Antimicrobial dosing in obese patients.

Although the dose of some drugs is commonly adjusted for weight, weight-related dosage adjustments are rarely made for most antimicrobials. We reviewed the English-language literature on antimicrobial pharmacokinetics and dosing in obesity. Although there are many potential pharmacokinetic consequences of obesity, the actual effect on the pharmacokinetics and clinical efficacy of most antimicrobials is unknown. Since approximately 30% of adipose is water, an empirical approach is use of the Devine formula to calculate ideal body weight (IBW), to which is added a dosing weight correction factor (DWCF) of 0.3 times the difference between actual body weight (ABW) and IBW (IBW + 0.3 x [ABW-IBW]) to arrive at a weight on which to base dosage of hydrophilic antibiotics. No studies confirm this approach for beta-lactam drugs. Clinical studies suggest a DWCF of approximately 0.40 for aminoglycosides and 0.45 for quinolones. Final dosage adjustments for antimicrobials with a narrow toxic-therapeutic window should be based on serum concentrations.

Animals↗

PubMed2001

Simultaneous optimization of cryoprobe placement and thermal protocol for cryosurgery.

We demonstrate that it is possible to simultaneously optimize multiple cryoprobe placements and their thermal protocol for one freeze-thaw cycle. A numerical optimization algorithm is used and three different forms of objective function are examined in terms of algorithm convergence rate, minimum value of the chosen objective function, temperature-volume histograms and isotherm distributions. The optimization results depend on the initial values of the variables, the form of the objective function, optimization goals and the mathematical method adopted for gradient calculation. The proposed optimization model offers significant advantages over the previously reported semi-empirical approach to conformal cryotherapy, such as the ability to handle an unlimited number of variables and eliminating the need for the user input between iterations, thereby reducing, if not removing, the subjectivity of cryosurgery treatment planning.

Algorithms↗

PubMed2004

Uncertainty in estimating probability of causation in a cross-sectional study: joint effects of radiation and hepatitis-C virus on chronic liver disease.

Exposure to other risk factors is an important consideration in assessing the role played by radiation in producing disease. A cross-sectional study of atomic-bomb survivors suggested an interaction between whole-body radiation exposure and chronic hepatitis-C viral (HCV) infection in the etiology of chronic liver disease (chronic hepatitis and cirrhosis), but did not allow determination of the joint-effect mechanism. Different estimates of probability of causation (POC) conditional on HCV status resulted from additive and multiplicative models. We therefore estimated the risk for radiation conditional on HCV status using a more general, mixture model that does not require choosing between additivity or multiplicativity, or deciding whether there is interaction, in the face of the large uncertainty. The results support the conclusion that POC increases with radiation dose in persons without HCV infection, but are inconclusive regarding individuals with HCV infection, the lower confidence bound on estimated POC for radiation with HCV infection being zero over the entire dose range. Although the mixture model may not reflect the true joint-effect mechanism, it avoids restrictive model assumptions that cannot be validated using the available data yet have a profound influence on estimated POC. These considerations apply more generally, given that the additive and multiplicative models are often used in POC related work. We therefore consider that an empirical approach may be preferable to assuming a specific mechanistic model for estimating POC in epidemiological studies where the joint-effect mechanism is in doubt.

Cross-Sectional Studies↗

PubMed2001

Aerosols and anti-infectious agents.

Anti-infectious agents such as pentamidine, antibiotics (mainly colistine and aminoglycosides), and amphotericin B can be administered by aerosol. Apart from pentamidine and Tobi, this route of administration is not officially approved and it constitutes an empirical approach, which has benefited from recent research summarized hereafter. The most fundamental question is related to the potentially deleterious effects of nebulization processes, especially ultrasound, on the anti-infectious properties of the drugs. Colimycin, which was chosen as a reference because its polypeptide structure makes it unstable a priori, proved to be resistant to high frequency ultrasound, which is encouraging for other molecules such as aminoglycosides or betalactamins. The nebulizer characteristics also have to be taken into account. An aerosol can be produced from an amphotericin B suspension and from colistine using both an ultrasonic nebulizer and a jet nebulizer. Differentiating between good and bad nebulizers is not dependent upon the physical process involved to nebulize the drug, but on the intrinsic characteristics of the device and its performance with a known drug. The inhaled mass of an aerosol in the respirable range must be high and dosimetric nebulizers represent significant progress. Finally, administration of anti-infectious aerosols requires a new pharmacological approach to monitor treatment, and urinary assays are promising for this purpose.

Administration, Inhalation↗

PubMed1997

Dosimetric considerations in the radioiodine treatment of macrometastases and micrometastases from differentiated thyroid cancer.

When macrometastases are delineated clearly using current radiographic techniques and/or physical examination and can be shown to concentrate 131I, the therapeutic activity to be administered may be determined quantitatively. Administrations of 131I that will deliver 30,000 rad to residual thyroid tissue or 10,000 +/- 2,000 rad to lymph node metastases will ablate them successfully 80% of the time, and bone marrow depression that is severe enough to require specialized treatment will be avoided if the whole blood dose from a single administration does not exceed 200 rad. When micrometastases are detected only by diagnostic radioiodine imaging and/or elevations of serum thyroglobulin levels, and when a clinical decision is made to treat them with radioiodine, then 131I may not be the isotope choice. With small lesions < 0.05 mm in diameter, the lower energy emissions of 125I therapy may be more suitable. With the advent of alternative methods of patient preparation for radioiodine therapy, empiric approaches that were derived from experience with endogenously hypothyroid patients will require full re-evaluation. Approaches based on quantitative radiodosimetric calculations will continue to be valid because they already consider individual differences in radioiodine kinetics.

Humans↗

PubMedDate not supplied

Anaerobes: problems and controversies in bacteriology, infections, and susceptibility testing.

Three key questions are discussed in this manuscript: (1) What is the clinical relevance of anaerobic bacteriology? (2) How can the microbiologist, with limited and decreasing resources, perform reliable, detailed studies of anaerobic bacteriology? (3) When and how should susceptibility testing be done with anaerobes? If the clinician knows the usual bacteriology of various types of infection and how this may be modified by pathophysiologic processes in the host or by prior therapy, he/she can use a logical empiric approach to treatment of the patient. As to the microbiologist's dilemma, it is not realistic or rational for a microbiologist in a nonteaching hospital to do detailed bacteriologic studies and routine anaerobic susceptibility testing. The resources available should be committed primarily to the patient who is seriously ill. Such allocation of resources, of course, requires repeated and effective communication between microbiologist and clinician.

Bacteria, Anaerobic↗

PubMed1988

Age differences in social network participation.

Differences in participation in social networks were analyzed as a function of age, drawing on a theoretical model of substitution processes. Using an empirical approach from the study of participation in voluntary organizations, I separated the direct effects of age from indirect effects via age-based declines in resources. The results show that a substantial proportion of the age-based decrease in level of activity in social networks was due to declines in resources, but similar analyses for the sources of participation in networks showed effects of age that persisted after controlling for resources. These results point to some important distinctions among measures of social networks.

Aged↗