Showing papers by "University of Kansas published in 1978"

Multiple-probe technique: a variation on the multiple baseline.

Abstract: Multiple-baseline and probe procedures are combined into a “multiple-probe” technique The technique is designed to provide a thorough analysis of the relationship between an independent variable and the acquisition of a successive-approximation or chain sequence It provides answers to the following questions: (1) What is the initial level of performance on each step in the training sequence? (2) What happens if sequential opportunities to perform each next step in the sequence are provided before training on that step? (3) What happens when training is applied? (4) What happens to the performance of remaining steps in the sequence as criterion is reached in the course of training each prior step? The technique features: (1) one initial probe of each step in the training sequence, (2) an additional probe of every step after criterion is reached on any training step, and (3) a series of “true” baseline sessions conducted just before the introduction of the independent variable to each training step Intermittent probes also provide an alternative to continuous baseline measurement, when such measurement during extended multiple baselines (1) may prove reactive, (2) is impractical, and/or (3) a strong a priori assumption of stability can be made

Microwave Backscatter Dependence on Surface Roughness, Soil Moisture, and Soil Texture: Part I-Bare Soil

Abstract: This is the first in a series of two papers on the use of active microwave remote sensing for measuring the moisture content of bare (Part I) and vegetation-covered (Part II) soil. An experimental program was conducted to evaluate the response of the backscattering coefficient to soil moisture content as a means to specify radar system parameters for future airborne and/or spaceborne soil moisture mappers. Particular attention was paid to the effects of surface roughness, and a preliminary examination of the role of soil texture was performed. The results of this investigation confirm the findings of a previous experiment [1] which concluded that the effects of surface roughness can be minimized by operating at a frequency in the neighborhood of 5 GHz over the 7-17° angle of incidence range. The precision with which soil moisture in the surface soil layer can be estimated is comparable to the precision of the ground-truthed estimate. Because the moisture in the surface layer is highly correlated to the subsurface moisture, it was not possible to determine experimentally the effective depth of the layer responsible for the observed radar backscatter.

Lateralization of norepinephrine in human thalamus

Abstract: Norepinephrine has a strongly lateralized distribution in the human thalamus. In the pulvinar region the left hemisphere is rich in norepinephrine, whereas in the somatosensory input area the right hemisphere has a higher concentration of this catecholamine. Such naturally occurring left-right differences in concentration of a neurotransmitter represent a new aspect of hemispheric specialization.

Island area and body size of insular mammals: evidence from the tri-colored squirrel (callosciurus prevosti) of southeast asia.

Abstract: The presence of Pleistocene elephants on Crete only 1 m in shoulder height, of giant rodents on Caribbean Islands, and of other equally remarkable dwarf and giant mammals, has prompted a variety of responses from their startled discoverers. Most of the mechanisms suggested for their origins are simplistic-usually a single factor, ranging from extreme food deprivation to isolation of antediluvian species. To my knowledge, no one has described adequately either the pattern of variation of mammals on islands, or synthesized the many suggested causes (Van Valen, 1973). This paper is an initial attempt to redress this deficiency. It is not intended as a thorough review; rather, it presents significant new data, briefly summarizes trends in body size of mammals, and presents a causal model of body size evolution in insular mammals. It is possible that the processes and patterns discussed here apply to other animals but I have directed my studies to maimmals alone. Each topic discussed below is worthy of a lengthy review, and it is my hope that this paper will stimulate additional research and discussion. During a study of the systematics of Callosciurus prevosti, the tri-colored squirrel of Malaysia, Indonesia, and peninsular Thailand, it became evident that body size of these squirrels was related to the size of the island on which the squirrels lived. This observation stimulated a more detailed study of size variation in these squirrels and led to the present paper. Body size of C. prevosti is discussed at the beginning of the paper, because variation in this species provided insight into the evolution of body size of insular mammals and formed the basis of my hypotheses and models. The biology of C. prevosti is poorly known. Externally tri-colored.squirrels resemble the familiar North American tree squirrels but are more brightly colored. Most populations have a black dorsum and tail, a broad white lateral stripe, and a red venter; many have a prominent shoulder patch which may be black, gray, red, white, or a mixture of these. In Selangor, Malaysia, tri-colored squirrels nested in trees and fed on coconut and rubber seeds, and oil palm fruit (Harrison and Traub, 1950; Harrison, 1962). Davis (1962) stated that in Sabah, North Borneo, they were found in primary and old logged forest where they inhabited chiefly the smaller trees of the middle story. Stomach contents consisted of pulpy fruit and about 5% insect matter, chiefly ants and termites. Three pregnant females taken on 20 June, 24 June, and 2 August had two, two, and three embryos, respectively. At Bukit Lanjong, West Malaysia, they have been seen feeding on the fruit of fig trees (Ficus) in the upper story (MacKinnon and MacKinnon, 1974:36). Nothing definite is known of the predators or competitors of these squirrels. ' Parts of this study were carried out while the author was resident at the Division of Mammals, Smithsonian Institution, Washington, D.C. 20560, and the Bell Museum of Natural History, University of Minnesota, Minneapolis, Minnesota 55455.

Multilocus Systems in Evolution

Abstract: Population studies of genetic variation and microevolution are classically discussed in terms of changes in gene frequencies and the maintenance of polymorphic loci that can be identified by Mendelian analyses. In recent years, however, a great deal of attention has been given to the evolutionary dynamics and polymorphisms of interacting and linked loci (e.g., Clegg et al., 1972; Lewontin, 1974; Karlin, 1976). The special properties of multilocus systems, namely, gene interaction and linkage, were first briefly considered in theory by Fisher (1930) and Wright (1932). Fisher discussed in particular the role of modifiers in the evolution of dominance and clearly recognized the importance of linkage in the evolution of interacting polymorphisms. Wright proposed an intermediate optimum model in which natural selection favors intermediate phenotypes over the extremes for a continuous metric trait and emphasized the role of linkage in the makeup of gametic arrays.

Clinical pharmacokinetics of methotrexate

Abstract: The absorption of methotrexate following intramuscular injection and oral administration of small doses (>30mg/m2) is rapid and complete, whereas with oral doses in excess of 80mg/m2 absorption is less than complete. Pretreatment with oral neomycin decreases and with kanamycin increases the gastrointestinal absorption of oral methotrexate. The plasma disposition of methotrexate is multiexponential. Due to differences in sampling schedule and assay methods, widely varying estimates of elimination half-life (tJ/2β of 6 to 69 hours of methotrexate have been reported. The long half-life may either be due to enterohepatic circulation of methotrexate and/or its metabolites or a slow elimination of dihydrofolate reductase (DHFR) bound methotrexate. The plasma clearance of methotrexate following small clinical doses is about 80ml/min, but may become saturated at high doses (20g). During high dose infusions, the peak plasma level is proportional to doses up to 200mg/kg. Methotrexate is transported across cellular membranes via a carrier-mediated active type process. At high concentrations, when the carrier route is saturated, passive diffusion assumes greater importance. Methotrexate is not highly bound to plasma proteins (∼50%). However, being highly ionised at physiological pH, the drug does not accumulate in the cerebrospinal fluid to any appreciable extent, necessitating intrathecal administration in the treatment of cerebral and meningeal metastases. Renal excretion is the major route of elimination for methotrexate (∼80% ); the drug being actively secreted in the renal tubule by the general organic acid transport system. Hence, the renal clearance of methotrexate is decreased by the concomitant administration of organic acids, such as salicylate. The renal clearance of methotrexate is correlated with endogenous creatinine clearance which may provide a guideline to dosage adjustments according to renal function and age. With high dose methotrexate, routine administration of fluid and/or bicarbonate is recommended to prevent intratubular precipitation of the drug. Biliary excretion of methotrexate constitutes less than 10% of the administered dose. Other extrarenal routes of excretion such as secretion into human breast milk and saliva are negligible. About a third of an oral dose of methotrexate is metabolised by intestinal bacteria during absorption. The major metabolite is 4-amino-4-deoxy-N10-methylpteroic acid. Small amounts (<11%) of 7 -hydroxymethotrexate have also been found in urine of patients receiving high dose methotrexate therapy. Except for the poly-γ-glutamates, all of the reported metabolites are less effective than methotrexate as an inhibitor of dihydrofolate reductase. As determined by inhibition of DNA synthesis, normal tissues are sensitive to low levels of methotrexate (∼10−8M) Furthermore, toxicity with methotrexate is related to duration of exposure as well as to the dose or plasma concentration. Impurities, such as methopterin and other byproducts of the synthetic process have been found in commercial parenteral dosage forms of methotrexate. The clinical significance of these impurities requires further study. For a phase-specific chemotherapeutic agent such as methotrexate, effective plasma levels of the drug should be maintained during the proliferative phase of the tumour cell cycle to achieve a maximum cytotoxic effect. Monitoring the plasma level of methotrexate, particularly during high dose therapy, may provide information regarding impending toxicity and the need for extended citrovorum factor rescue.

Leaf isozymes as genetic markers in citrus

Abstract: The genetic control of isozymes from Citrus and its near relatives was determined for three gene/ enzyme systems: glutamate oxaloacetate transaminase, phosphoglucose isomerase and phosphoglucose mutase. These enzymes are controlled by four genes having 19 codominant alleles, 12 of which occur in Citrus subg Citrus. Formal genetic studies were carried out with F1 biotypes and F1 populations of known origin. When biotypes were grouped into traditionally recognized species to examine genetic affinities within and between species, a remarkable pattern of uniformity of genotype combinations was found within a species, and every species had an unique combination. Because many economically important cultivars produce asexual(nucellar) as well as sexual(zygotic) embryos, a central problem of the breeder is to distinguish these when plants are young, long before fruiting. Isozyme markers can be used with varying degrees of efficiency, depending on the genotypes of the particular parents, to distinguish nucellar seedlings from those of zygotic origin. THERE have been several attempts to render a taxonomy reflecting species relationships in Citrus, a diverse and difficult group comprised of two subgenera, Citrus and Papeda (Swingle, 1943; Swingle and Reece, 1967). The former includes all the edible cultivars. Papeda includes six species with non-edible fruits. The number of species to be recognized in Citrus subg Citrus, and which biotypes to include in which species, constitute the central problems in Citrus taxonomy. The best known taxonomies, those of Swingle (1943) and Tanaka (1969), differ widely in the number of admitted species. Swingle recognized 16 in Citrus, Tanaka, 159. At another extreme, Scora (1975) and independently, Barrett and Rhodes (1976), recognized just three basic species exclusive of those of the subgenus

Ultraviolet reflection and its behavioral role in the courtship of the sulfur butterflies Colias eurytheme and C. philodice (Lepidoptera, Pieridae)

Abstract: 1. The courtship behavior of the sulfur butterflies, Colias eurytheme and C. philodice (Lepidoptera, Pieridae), was studied in the field and in large outdoor flight cages. Experiments were performed to investigate the nature of releasers of male courtship behavior and to determine the basis of conspecific mate recognition by females. 2. The courtship of these species is extremely brief and does not involve the elaborate displays characteristic of many other butterflies. Mature females employ a mate-refusal posture (Fig. 10) to effect mate selection against, and insure reproductive isolation from, non-conspecific males. The same behavior is also employed by unreceptive females in response to conspecific males. 3. Males rely on visual cues to locate and identify females. They respond to paper dummies of the appropriate color (Figs. 15 and 16) and attempt to mate with them (Fig. 7B). No chemical stimuli are necessary to elicit this behavior. The most attractive dummies closely match the yellowish green, ultraviolet-absorbing color of the female ventral hind wing (Fig. 17). Ultraviolet reflection added to an otherwise attractive dummy (Fig. 18A) strongly inhibits male approaches (Fig. 18B). One function of the ultraviolet reflection of male C. eurytheme (Fig. 1) is its use as an inhibitory signal directed to other males. This signal is displayed by individual males to communicate their sex to others, as well as by males in copulo to inhibit courtship attempts of intruders (Fig. 11). 4. Visible color differences between C. eurytheme (orange) and C. philodice (yellow) males play no role in mate selection by females of either species (Table 8). The ultraviolet reflection difference between male C. eurytheme (reflecting) and male C. philodice (absorbing) (Figs. 1 and 8) is used as a mate-recognition signal by females of C. eurytheme and in this way functions as a component of the system of isolating mechanisms in this species. C. philodice females do not respond to ultraviolet reflection patterns in any way and appear not to use any visual stimuli in mate selection (Table 8). 5. Females of both species rely on chemical cues for conspecific mate recognition. The chemical signals are not associated with so-called ‘androconial’ scales (Fig. 19) located in the black borders of the male wings. These scales are not necessary for successful courtship (Table 7) and no sexual function can presently be ascribed to them. For these and other reasons, we suggest that the term ‘androconia’ not be used for the black border scales of male Colias. No species-recognition pheromones are associated with the dorsal discal region of the male's wings (Table 6), but olfactory signals may be associated with their ventral surfaces, the anterior or posterior margins of their dorsal surfaces, the legs, or the body. 6. All male F1 hybrids are ultraviolet-absorbing. F1 hybrid females, derived from crosses between female C. eurytheme and male C. philodice, display the same mate-selection behavior as is characteristic for butterflies of their paternal parents' species (Table 4).

Competitive Interactions Between Neotropical Pollinators and Africanized Honey Bees

Abstract: The Africanized honey bee, a hybrid of European and African honey bees, is thought to displace native pollinators. After experimental introduction of Africanized honey bee hives near flowers, stingless bees became less abundant or harvested-less resource as visitation by Africanized honey bees increased. Shifts in resource use caused by colonizing Africanized honey bees may lead to population decline of Neotropical pollinators.

Intraspecific defense: advantage of social cooperation among paper wasp foundresses

Abstract: Foundress associations and high frequencies of conspecific nest usurpation are most common where densities of Polistes metricus are high. Here nest usurpation occurs primarily in single-foundress colonies resulting in multiple-foundress colonies having significantly greater productivities than single-foundress colonies. This is not true at low densities. Conspecific pressures and not predation or parasitism provide an advantage to cooperating wasp foundresses in P. metricus.

Purification and chemical characterization of the heat-stable enterotoxin produced by porcine strains of enterotoxigenic Escherichia coli.

Abstract: Heat-stable enterotoxin (ST) produced by porcine strains of enterotoxigenic (ENT+) Escherichia coli has been purified to apparent homogeneity by sequential ultrafiltration, acetone fractionation, preparative gel electrophoresis, diethylaminoethyl Bio-Gel A ion-exchange chromatography, and Bio-Gel P-10 gel filtration. The enterotoxin, purified more than 1,500-fold, exhibited a molecular weight of 4,400, as determined by both sodium dodecyl sulfate-gel electrophoresis and gel filtration. A molecular weight of 5,100, representing 47 residues, was calculated from amino acid analysis data. The amino acid content was distinctive, with an unusually high proportion of cystines and few hydrophobic amino acids. A single amino-terminal residue, glycine, was observed. Purified ST was stable to heating (100°C, 30 min) and did not lose biological activity after treatment with Pronase, trypsin, proteinase K, deoxyribonuclease, ribonuclease, and phospholipase C. Periodic acid oxidation and several organic solvents (acetone, phenol, chloroform, and methanol) had no effect on the biological activity of ST. Further, purified ST was stable to acid treatment at pH 1.0 but lost biological activity at pH values greater than 9.0. Neither lipopolysaccharide nor lipid contamination was evident in purified preparations. A characteristic absorption spectrum was observed during the course of the purification, which shifted from a maximum at 260 nm in crude preparations to 270 nm for the purified toxin. Antiserum obtained from rabbits immunized with ST or ST coupled to bovine serum albumin neutralized the action of the enterotoxin in suckling mice; however, passive hemagglutination and hemolysis titer assays suggested that ST is a poor antigen.

Numerical computation of scattering from a perfectly conducting random surface

Abstract: A one-dimensionally rough random surface with known statistical properties was generated by digital computer. This surface was divided into many segments of equal length. The moments method was applied to each surface segment assuming perfect conductivity to compute the induced surface current and subsequently the backscattered field due to an impinging plane wave. The return power was then calculated and averaged over different segments. Unlike numerical computations of scattering from deterministic surfaces, problems of stability (as defined by Blackman and Turkey [11]) and convergence of the solution exist for random surface scattering. It is shown that the stability of the numerically computed estimate of the backscattered average power depends on N , the total number of disjoint surface segments averaged; \Delta x , the spacing between surface current points; D , the width of each surface segment; and g , the width of the window function. Relations are obtained which help to make an appropriate choice of these parameters. In general, choices of \Delta x, D , and g are quite sensitive to the incident wavelength and the angular scattering properties of the surface.

Follicular Atresia in the Ovaries of Nonmammalian Vertebrates

Abstract: Publisher Summary Follicular atresia (or degeneration) is a widespread phenomenon occurring in the ovaries of vertebrates including humans, irrespective of age, stage of the reproductive cycle, environmental conditions (season, temperature, light, rainfall, and availability of food), and the general health of the individual animal. Atresia also occurs under various experimental conditions such as hypophysectomy, irradiation, and administration of antigonadotropic substances. However, very little attention has been given to the study of follicular atresia, particularly in the ovaries of nonmammalian vertebrates. The problem of follicular atresia is not fully resolved even in the mammalian ovary. It is not known, for instance, why some oocytes are able to develop and undergo ovulation while their neighbors undergo degeneration. The precise mechanism(s) underlying such a germinal selection is not well understood. In the past, there have been a few reviews dealing with some aspect or another of follicular atresia in one or more classes of vertebrate ovaries. It is apparent from these studies that there is much confusion and controversy with regard to (1) the mode of atresia, (2) the endocrine nature of atretic follicles, (3) the consequences of follicular atresia, if any, and (4) the terminology used. This chapter discusses follicular atresia in the ovaries of nonmammalian vertebrates based on the histological, histochemical, ultrastructural, and biochemical findings of recent years. The consequences of this degenerative process, the endocrine capacity of the atretic follicles, and the possible environmental and hormonal factors affecting or controlling follicular atresia are discussed.

Intracellular study of electrical activity of Auerbach's plexus in guinea-pig small intestine.

Abstract: Intracellular recording revealed two general categories of ganglion cells in Auerbach's plexus. The characteristics of one category were relatively low resting potentials, high input resistance, discharge of spikes throughout a depolarizing current pulse, stimulus-evoked synaptic potentials and spontaneous electrical activity. Characteristics of the second category were high resting potentials, low input resistance, spikes only at the onset of a depolarizing current pulse and long duration hyperpolarizing after-potentials. Responses to extracellular electrical stimulation of the ganglia and interganglionic fiber tracts consisted of electrotonic spread of spikes from the processes to the cell soma, somal action potentials and depolarizing and hyperpolarizing responses that were probably EPSPs and IPSPs. Some of the neurons which received excitatory synaptic input responded with a prolonged train of spikes that outlasted by many seconds the duration of the stimulus to the fiber tract. Spontaneous electrical activity consisted of single EPSPs, patterned bursts of spikes that originated in the cell processes and spread electrotonically to, the recording site, IPSPs and action potentials. The burst-type activity showed periodic conversions from a burst pattern to a trainlike pattern of continuous discharge. Spontaneous discharge of single action potentials was superimposed upon a background of continuous synaptic input to the cell. Spontaneously occurring hyperpolarizing potentials were converted to depolarizing potentials when the membrane was hyperpolarized by current injected through the recording electrode.

Slow synaptic excitation mediated by serotonin in Auerbach's plexus.

Abstract: THE application of low concentrations of substance P to guinea-pig myenteric neurones has been reported by Katayama and North to produce depolarisation associated with an increase in input resistance and augmented excitability1. On this basis, they suggested that substance P may be involved in the production of the slow excitatory postsynaptic potential (e.p.s.p.) which can be evoked in myenteric neurones by electrical stimulation of the interganglionic connectives2. In this report, we show that application of serotonin (5-HT) mimics the slow e.p.s.p., and present several lines of evidence which suggest that 5-HT is a more likely candidate for the neurotransmitter of the slow e.p.s.p.

A Scatter Model for Leafy Vegetation

Abstract: A model for vegetation scatter is developed using the first-order renormalization method. The vegetated medium is taken to be an inhomogeneous medium characterized by a random permittivity function with a cylindrically symmetric fast-decaying correlation function. The permittivity of the vegetation (taken to be a combination of water and some solid material) is estimated by a mixing formula after de Loor [13], and the permittivity of the vegetated medium (taken to be a combination of vegetation and air) is estimated using a formula by Pierce [16]. The backscattering coefficient from such a model is computed as a function of the incidence angle, the frequency, and the moisture content of the vegetation. Comparisons are made with measured data from soybeans, alfalfa, and corn. The agreements obtained in both the absolute levels and the angular trends of the backscattering coefficient appear to justify both the permittivity and the scatter model for vegetation.

Pregnancy outcome of patients treated for Hodgkin's disease: a controlled study.

Abstract: Normal reproduction prosepcts for Hodgkin's disease patients are unknown. This study compares the outcome of 93 pregnancies in 48 patients with 228 pregnancies in 69 sibling controls. No statistically significant differences for spontaneous abortions or abnormal offspring were noted comparing all patients with all controls or 35 irradiated patients with all controls. Pregnancy outcome of 13 patients who received both irradiation and chemotherapy prior to pregnancy appeared to be compromised compared to controls. Wives of male patients in this category were more likely to have spontnaeous abortions than wives of male controls; female patients in this category were significantly more likely to produce abnormal offspring than were female controls (p = 0.047). In this series of patients therapeutic irradiation alone did not appear to jeoparadize posttreatment reproduction in fertile Hodgkin's disease patients but in the smaller group of patients who received both irradiation and chemotherapy the reproduction picture was statistically not as good.

Simultaneous multispacecraft observations of energetic proton bursts inside and outside the magnetosphere

Abstract: Energetic proton bursts were observed simultaneously on Imp 6, 7, and 8 both inside and outside the earth's magnetosphere during the period October 1972 through August 1974. It is found that proton bursts are present nearly simultaneously in the vicinity of the outer belt trapping boundary, in the low-latitude magnetotail, in the magnetosheath, and upstream from the bow shock. Large intensity differences, time delays, and differences in energy spectra recorded by the three spacecraft are described. It is suggested that energetic protons and electrons are probably accelerated inside the plasma sheet and propagate to various regions both inside and outside the magnetosphere.

A clinical study of forces generated by the intrinsic muscles of the index finger and the extrinsic flexor and extensor muscles of the hand

Abstract: A study of the forces generated by the intrinsic muscles of the index finger and coordinating muscles of the hand found that the intrinsic muscles of the index finger contributed combined forces equivalent to approximately 80% of those generated by the flexor profundus and superficialis, and to 73% of the moment for the motion of metacarpopalangeal flexion with simultaneous interphalangeal joint extension. No current tendon transfer operation can correct this deficit, though several supply sufficient force at the metacarpophalangeal joint to counterbalance the extrinsic extensors.

Steroid and Gonadotropin Levels During the Luteal-Follicular Shift of the Cyclic Hamster

Abstract: This study was designed to correlate ovarian and hormonal changes of cyclic hamsters during the period of luteal regression and rising dominance of antral follicles. Cyclic hamsters (8/group) were decapitated at 2 h intervals between Day 2 at 1000 h and Day 3 at 1000 h; Day 1 is defined as the day of ovulation. Serum was collected for RIA of gonadotropins and steroids. From 1 ovary, corpora lutea (CL) and the nonluteal ovary (NLO) were saved for steroid RIA and the remaining ovary was prepared for histology. The diameter of antral follicles steadily increased from 389 to 437 im during Days 2-3, and the number/ovary increased from 3 at 1000 h Day 2 to 11 at 2400 h Day 2. However, by 1000 h Day 3 the number of antral follicles had declined to 5/ovary. The highest level of serum progesterone (P) occurred at 2000 h Day 2; thereafter, the levels declined abruptly to less than 1 ng/ml by 0400 Day 3. The concentration of luteal P decreased gradually between 2000 h Day 2 and 0400 h Day 3 2 h later there was a drastic decline correlating with an influx of leukocytes into the CL. On Day 2, although antral follicles were present, serum estradiol (E2) was very low. However, estradiol increased at 0400 h Day 3 associated with increased concentration of E2 and androgen in NLO. During the 24 h period, the most striking difference in serum levels of FSH, LH and prolactin was the peak of all 3 hormones at 2200 h Day 2, 4 to 6 h before any significant changes in the serum levels of P or E2. The results demonstrate that the shift from the luteal phase to the follicular phase is a gradual process involving concomitant declining levels of P and increasing levels of E2. The results suggest that the transitory increase of gonadotropins and/or declining levels of P are causally related to enhanced follicular secretion of E2 and androgen.

Paradigm Development in the Social Sciences: A Proposed Research Strategy

Abstract: A paradigm development strategy of research consists of: fitting data into a theoretical framework with general laws to explain the data; deducing hypotheses from the general laws; and subjecting these hypotheses to empirical test. Deductive-nomological reasoning, crucial experiments, and typology of experimental control strategies are presented. Methods of strong inference are discussed, followed by a description of paradigm development research. Examples illustrate the strategy of paradigm research.