Showing papers by "Vanderbilt University published in 1976"
TL;DR: The contraction produced by aggregating platelets was unlike those produced by prostaglandins E2, F2alpha, G2, or H2, but resembled that evoked by thromboxane A2, which is formed by platelets during aggregation.
Abstract: When human platelets are aggregated by thrombin, material is released that rapidly contracts strips of spirally cut porcine coronary artery. Prevention of the contraction by indomethacin suggested mediation by a prostaglandin. The contraction produced by aggregating platelets was unlike those produced by prostaglandins E2, F2alpha, G2, or H2, but resembled that evoked by thromboxane A2, which is formed by platelets during aggregation.
505 citations
TL;DR: A method utilizing precipitation on filter paper has been used to isolate glycogen from homogenates of liver or isolated hepatocytes, and its efficiency and specificity make it very suitable for many studies involving radioactive tracer incorporation into glycogen.
415 citations
TL;DR: It appears that the therapeutic action of tricyclic antidepressants could be related to postsynaptic adaptive changes in the sensitivity of the noradrenergic adenylate cyclase receptor system rather than to acute presynaptic events.
Abstract: The response of the norepinephrine (NE) sensitive cyclic AMP generating system in slices of the rat limbic forebrain after both the acute and chronic administration of the tricyclic antidepressants desipramine (DMI) and iprindole as well as electroconvulsive treatment (ECT) was investigated. Neither the basal level of cyclic AMP nor the hormonal response to NE were altered after the administration of a single dose or short term treatment with DMI and iprindole. However, the administration of the antidepressants on a clinically more relevant time basis markedly reduced the sensitivity of the cyclic AMP generating system to NE. This change in sensitivity was not related to the levels of the drugs in brain. The response of cyclic AMP to NE was also reduced by ECT, but the onset of this action was shorter than that observed with the antidepressants. ECT also antagonized the enhanced response of cyclic AMP to NE following destruction of central adrenergic nerve terminals with 6-hydroxydopamine. It thus appears that the therapeutic action of tricyclic antidepressants could be related to postsynaptic adaptive changes in the sensitivity of the noradrenergic adenylate cyclase receptor system rather than to acute presynaptic events.
401 citations
TL;DR: In confluent cultures of HF cells, subject to density dependent inhibition of growth, hEGF was able to stimulate DNA synthesis more effectively than fresh calf serum, however, human EGF stimulated DNA synthesis in quiescent cultures, regardless of cell density.
Abstract: The effect of human epidermal growth factor (hEGF), a 5,400 molecular weight polypeptide isolated from human urine, on the growth of human foreskin fibroblasts (HF cells) was studied by measuring cell numbers and the incorporation of labeled thymidine. The addition of hEGF to HF cells growing in a medium containing 10% calf serum resulted in a 4-fold increase in the final density. The presence of hEGF also promoted the growth of HF cells in media containing either 1% calf serum or 10% gamma globulin-free serum. The addition of hEGF to quiescent confluent monolayers of HF cells, maintained in a medium with 1% calf serum for 48 hours, resulted in a 10- to 20-fold increase in the amount of 3H-thymidine incorporation after 20-24 hours. The stimulation of thymidine incorporation was maximal at an hEGF concentration of 2 ng/ml, was dependent on the presence of serum, and was enhanced by the addition of ascorbic acid. In confluent cultures of HF cells, subject to density dependent inhibition of growth, hEGF was able to stimulate DNA synthesis more effectively than fresh calf serum. Human EGF stimulated DNA synthesis in quiescent cultures, however, regardless of cell density. The addition of rabbit anti-hEGF inhibited all effects of this growth factor on HF cells.
381 citations
TL;DR: A comprehensive description of instrumental and theoretical methods employed to make accurate measurements of rotational correlation times using passage saturation transfer electron paramagnetic resonance (ST-EPR) is given in this paper.
Abstract: A comprehensive description is given of instrumental and theoretical methods employed to make accurate measurements of rotational correlation times using passage saturation transfer electron paramagnetic resonance (ST–EPR). Saturation transfer methods extend by several orders of magnitude the sensitivity of EPR to very slow motion; for example, for nitroxide spin labels, correlation times as long as 10−3 sec become accessible to measurement. Two ST–EPR detection schemes are discussed in detail: dispersion, detected 90° out of phase with respect to the 100 kHz field modulation, and absorption, detected 90° out of phase with respect to the second harmonic of the 50 kHz field modulation. The sensitivities of these configurations are illustrated with experimental spectra obtained from a system obeying isotropic Brownian rotational diffusion; namely, maleimide spin labeled human oxyhemoglobin in aqueous glycerol solutions. Two theoretical approaches, one employing coupled Bloch equations and the other utilizing the stochastic Liouville equation for the density matrix with the orientation variables treated by transition rate matrix or orthogonal eigenfunction expansion methods, are in excellent agreement with each other and with model system spectra. Both experimental and theoretical spectra depend on a number of relaxation processes other than rotational diffusion; consequently, considerable care must be taken to ensure the accuracy of measured rotational correlation times. Although the absorption method is currently the more sensitive and convenient one to apply with most conventional (commercial) spectrometers, the dispersion ST–EPR method is potentially more powerful, providing strong motivation for future technological efforts to decrease noise levels in dispersion experiments.
366 citations
TL;DR: The results suggest that a produce of the Sarcoma virus genome specifically changes cell EGF receptors; the sarcoma gene product may, then, be functionally related to EGF.
Abstract: Normal cells in culture have membrane receptors for epidermal growth factor (EGF); EGF stimulates cells to divide by binding to these receptors. Cells transformed by murine and feline sarcoma viruses rapidly lose the ability to bind EGF, whereas cells transformed by the DNA tumour viruses, polyoma and SV40, or infected with non-transforming RNA tumour viruses have normal levels of functional EGF receptors. The results suggest that a produce of the sarcoma virus genome specifically changes cell EGF receptors; the sarcoma gene product may, then, be functionally related to EGF.
361 citations
TL;DR: This reaction is useful for the colorimetric estimation of indole-3-acetic acid in biological mixtures and the colored complex (whose chromophore probably has similar structure as the product of the Salkowski's reaction) is relatively stable in light.
315 citations
TL;DR: The catalytic subunit of bovine liver cyclic AMP-dependent protein kinase (EC2.7.1.37) was purified essentially by the method of Reimann & Corbin and determined to be monodisperse.
Abstract: 1. The catalytic subunit of bovine liver cyclic AMP-dependent protein kinase (EC2.7.1.37) was purified essentially by the method of Reimann & Corbin [(1976) Fed. Proc. Fed. Am. Soc. Exp. Biol. 35, 1384]. 2. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, sedimentation-velocity centrifugation and sedimentation-equilibrium centrifugation showed that the catalytic subunit was monodisperse. Polyacrylamide-gel isoelectric-focusing electrophoresis revealed the presence of at least three isoenzyme forms of catalytic subunit activity with slightly different pI values (6.72, 7.04 and 7.35). 3. Physical properties of the catalytic subunit were determined by several different methods. It had mol.wt. 39000-42000, Stokes radium 2.73-3.08 nm, so20.w 3.14S, f/fo 1.19-1.23 and, assuming a prolate ellipsoid, axial ration 4-5. 4. Amino acid analysis was performed on the catalytic subunit. It had one cysteine residue/molecule which was essential for activity. Inhibition by thiol-specific reagents was partially prevented by the presence of ATP-Mg2+. 5. The circular-dichroic spectrum showed the catalytic subunit contained 29% alpha-helical form, 18% beta-form and 53% aperiodic form. Near-u.v. circular dichroism showed the presence of aromatic residues whose equivalent molar ellipticity was greatly altered by the addition of ATP-Mg2+. 6. Kinetic experiments showed that the catalytic subunit had an apparent Km for ATP of 7 muM. 5'-Adenylyl imidodiphosphate inhibitied competitively with ATP with a Ki of 60 muM. The kinetic plot for histone (Sigma, type II-A) was biphasic showing 'high'-and 'low'-Km segments. Under assay conditions the specific activity of the catalytic subunit was 3 X 10(6) units/mg of protein. Of various metal ions tested, the catalytic subunit was most active with Mg2+.7. When assayed with histone (Sigma, type II-A) as substrate, the activity of the catalytic subunit was increased by non-ionic detergents or urea. No such activation was observed with casein as substrate.
272 citations
TL;DR: The data indicated that infants looked at the joy expression significantly more than at either the anger or neutral expressions, suggesting that infants are capable of discriminating emotion expressions earlier in their development than previous studies have implied.
Abstract: 24 infants, 12 4-month-olds and 12 6-month-olds, were repeatedly shown slides of 3 facial expressions. The expressions were previously judged by obervers to be indicators of joy, anger, and no emotion, respectively. The duration of the first visual fixation to each presentation of the slides was monitored for each subject. The data indicated that the infants looked at the joy expression significantly more than at either the anger or neutral expressions. The results suggest that infants are capable of discriminating emotion expressions earlier in their development than previous studies have implied.
262 citations
TL;DR: Testing the hypothesis that health-related information seeking is a joint function of a person's locus of control beliefs and the value placed on health found little evidence was found to support the proposition that subject differentially chose pamphlets according to author characieristics.
235 citations
TL;DR: Only subjects treated by IBT with a goal of controlled drinking engaged in a substantial amount of limited, non-problem drinking during the second year interval, and those subjects also had more abstinent days than subjects in any other group.
TL;DR: This model has been tested experimentally and appears to be valid and is a useful way to characterise the ability of the liver to irreversibly remove drug from the circulation in the absence of any flow limitation.
Abstract: For some drugs, delivery to the liver by the hepatic circulation is an important determinant of removal by this organ. Classical pharmacokinetic analyses cannot predict the changes produced by altering any of the biological determinants of drug elimination by the liver; hepatic blood flow, metabolic enzyme activity, drug binding and route of administration. However, with the use of a physiological model of hepatic drug elimination, such predictions can be made. This model has been tested experimentally and appears to be valid. Hepatic blood flow can vary over about a 4-fold range from half normal flow to twice normal flow. These variations are produced by physiological, pathological or pharmacological changes affecting the circulation. For drug clearance to be affected significantly by these changes in flow, the drug must be avidly removed by the liver as reflected in a high hepatic extraction ratio and intrinsic hepatic clearance. This latter term is a useful way to characterise the ability of the liver to irreversibly remove drug from the circulation in the absence of any flow limitation. The clearance of drugs with low intrinsic clearances will not be affected significantly by changes in liver blood flow.
TL;DR: Physiological tolerance does develop to the facilitation of self-stimulation behavior which the drug produces, and testing on the following day with no further drug administration showed a depression of responding indicating depression of the reward system of the brain.
Abstract: Existing reports of tolerance to the behavioral effects of d-amphetamine are most parsimoniously interpreted as reflecting behavioral adaptation to the disruptive effects of the drug rather than physiological tolerance. The present study shows that physiological tolerance does develop to the facilitation of self-stimulation behavior which the drug produces. Rats were trained to bar-press for electrical stimulation of the medial forebrain bundle and tested for facilitation of responding following the administration of 0.25 or 0.50 mg/kg d-amphetamine. Testing was terminated for 4 days during which increasing doses (1.0-12.0 mg/kg) of the drug were given. 16 h after the last injection, the test doses (0.25 or 0.50 mg/kg) no longer produced facilitation of self-stimulation. In addition, testing on the following day with no further drug administration showed a depression of responding indicating depression of the sensitivity of the reward system of the brain.
TL;DR: The owl monkey, as do other mammals, has Xand Y-cells in its lateral geniculate nucleus, and the vast majority of neurons in this nucleus was clearly composed of either Xor Ycells, but there was no activation by fast targets of appropriate contrast to excite the cell through the surround.
Abstract: The owl monkey, as do other mammals, has X- and Y-cells in its lateral geniculate nucleus. X-cells are found in the parvocellular laminae; Y-cells, in the magnocellular laminae.
TL;DR: Peterson as discussed by the authors proposes revitalizing the sociology of culture by asking how culture is deliberately produced, and finds that numerous unexplored communalities in the production of art, science, and religion are revealed.
Abstract: Peterson proposes revitalizing the sociology of culture by asking how culture is deliberately produced. Once several inhibitions to comparative analysis are overcome, numerous unexplored communalities in the production of art, science, and religion are revealed. These suggest a genetic theory of the role of culture for society.
TL;DR: The adenine analogue-binding protein was detected in crude tissue supernatant fractions of bovine and rat liver and differed from the regulatory subunit of cyclic AMP-dependent protein kinase in many of its properties.
Abstract: 1. At least two classes of high-affinity cyclic AMP-binding proteins have been identified: those derived from cyclic AMP-dependent protein kinases (regulatory subunits) and those that bind a wide range of adenine analogues (adenine analogue-binding proteins). 2. In fresh-tissue extracts, regulatory subunits could be further subdivided into ‘type I’ or ‘type II’ depending on whether they were derived from ‘type I’ or ‘type II’ protein kinase [see Corbin et al. (1975) J. Biol. Chem. 250, 218-225]. 3. The adenine analogue-binding protein was detected in crude tissue supernatant fractions of bovine and rat liver. It differed from the regulatory subunit of cyclic AMP-dependent protein kinase in many of its properties. Under the conditions of assay used, the protein accounted for about 45% of the binding of cyclic AMP to bovine liver supernatants. 4. The adenine analogue-binding protein from bovine liver was partially purified by DEAE-cellulose and Sepharose 6B chromatography. It had mol.wt. 185000 and was trypsin-sensitive. As shown by competition and direct binding experiments, it bound adenosine and AMP in addition to cyclic AMP. At intracellular concentrations of adenine nucleotides, binding of cyclic AMP was essentially completely inhibited in vitro. Adenosine binding was inhibited by only 30% under similar conditions. 5. Rat tissues were examined for the presence of the adenine analogue-binding protein, and, of those examined (adipose tissue, heart, brain, testis, kidney and liver), significant amounts were only found in the liver. The possible physiological role of the adenine analogue-binding protein is discussed. 6. Because the adenine analogue-binding protein or other cyclic AMP-binding proteins in tissues may be products of partial proteolysis of the regulatory subunit of cyclic AMP-dependent protein kinase, the effects of trypsin and aging on partially purified protein kinase and its regulatory subunit from bovine liver were investigated. In all studies, the effects of trypsin and aging were similar. 7. In fresh preparations, the cyclic AMP-dependent protein kinase had mol.wt. 150000. Trypsin treatment converted it into a form of mol.wt 79500. 8. The regulatory subunit of the protein kinase had mol.wt. 87000. It would reassociate with and inhibit the catalytic subunit of the enzyme. Trypsin treatment of the regulatory subunit produced a species of mol.wt. 35500 which bound cyclic AMP but did not reassociate with the catalytic subunit. Trypsin treatment of the protein kinase and dissociation of the product by cyclic AMP produced a regulatory subunit of mol.wt. 46500 which reassociated with the catalytic subunit. 9. These results may be explained by at least two trypsin-sensitive sites on the regulatory subunit. A model for the effects of trypsin is described.
TL;DR: The visual system seems to utiliz a process similar to cross-correlation to detect coherent, position-invariant patterns of stimulation in random-dot patterns.
01 Jan 1976
TL;DR: This paper will review reasonably thoroughly and comprehensively the many observational properties of the remarkable RS CVn-type binaries and show that many of these same properties are observed in other types of binary systems.
Abstract: This paper will review reasonably thoroughly and comprehensively the many observational properties of the remarkable RS CVn-type binaries. In addition this paper will show that many of these same properties are observed in other types of binary systems.
TL;DR: The radioactive microsphere method was used to estimate simultaneoulsy the cardiac output and its distribution in the same rat by the use of an arterial reference sample obtained during microspheres distribution.
Abstract: The radioactive microsphere method was used to estimate simultaneously the cardiac output and its distribution in the same rat by the use of an arterial reference sample obtained during microsphere distribution. Sufficient microspheres were injected so that all counted samples contained more than 400 spheres. No haemodynamic changes occurred during microsphere injection. The results for cardiac output of 253 ± 11 ml/min per kg body weight agree with published estimates utilizing other techniques. The distribution of cardiac output also agrees with most published reports. This method should allow the rat to be conveniently used for certain haemodynamic studies when cardiac output and organ blood flow are necessary.
TL;DR: The date and circumstances of the first Greek settlements on the Black Sea are matters of considerable disagreement as mentioned in this paper, which is the result both of the scattered nature of the literary evidence on the subject, and of the dearth of archaeological evidence for Pontic settlements other than those on the western and northern shores.
Abstract: The date and circumstances of the first Greek settlements on the Black Sea are matters of considerable disagreement. This is the result both of the scattered nature of the literary evidence on the subject, and of the dearth of archaeological evidence for Pontic settlements other than those on the western and northern shores. A century ago it was commonly thought that although the great majority of colonies were sent out in the seventh and sixth centuries, Trapezus and Sinope, as our sources say or imply, were founded in the middle of the eighth. For a variety of reasons, among them an increased reliance on archaeologically secured dates, this view went out of favour, and opinion inclined toward the view that the Greeks did not enter the Black Sea at all until after 700. This view was both expressed in and supported by Rhys Carpenter's thesis that not until the penteconter was invented (an invention which he dated to the early seventh century) could the Greeks make head against the four-knot current which flows through the Bosporus from the Black Sea. Articles by B. W. Labaree and A. J. Graham, however, have undermined Carpenter's argument, and it is now once again not unusual to find references to Greek activity in the Black Sea before 700.
TL;DR: A backtracking algorithm for testing a pair of digraphs for isomorphism is presented and performs efficiently for a large class of graphs.
Abstract: A backtracking algorithm for testing a pair of digraphs for isomorphism is presented. The information contained in the distance matrix representation of a graph is used to establish an initial partition of the graph's vertices. This distance matrix information is then applied in a backtracking procedure to reduce the search tree of possible mappings. While the algorithm is not guaranteed to run in polynomial time, it performs efficiently for a large class of graphs.
TL;DR: The results provide further evidence for a regulatory mechanism in the CNS involving the noradrenergic receptor that adapts its sensitivity to NE in a manner inversely related to the degree of its stimulation by the catecholamine.
Abstract: — The noradrenergic cyclic AMP generating system in slices of the limbic forebrain of rats displays characteristics which are compatible with those of a central NE receptor. The cyclic AMP response to a Kmax concentration of NE (concentration of NE which elicits maximal increase in the level of cyclic AMP) is significantly enhanced in slices from reserpinized animals, although the Ka value of NE (concentration of NE eliciting half-maximum response) was not significantly changed. Chemosympathectomy with 6-hydroxydopamine (6-OHDA) significantly enhanced the activity of the system to NE and isoproterenol but not to adenosine and reduced the Ka value for NE. The changes in the reactivity of the cyclic AMP generating system following 6-OHDA administration appear to be related to a decrease in the availability of NE and not to that of other neurotransmitters as protection by desipramine (DMI) of noradrenergic neurons against the neurotoxic action of 6-OHDA prevented the development of supersensitivity to NE. Conversely, and independent of the actual concentration of NE in brain tissue, a persistent increase in the availability of NE caused by prolonged MAO inhibition lead to a marked decrease in the reactivity of the cyclic AMP generating system. The results provide further evidence for a regulatory mechanism in the CNS involving the noradrenergic receptor that adapts its sensitivity to NE in a manner inversely related to the degree of its stimulation by the catecholamine.
TL;DR: The effect of propranolol on heart rate is a predictable function offree drug concentration in man and that the contribution of individual variation in receptor sensitivity to differences in oral dosage requirement is minor compared to that of variations in bioavailability.
Abstract: The effects of plasma drug binding on the relationship between propranolol concentration and the antagonism of isoproterenol tachycardia have been investigated in 8 normal subjects and 8 hypertensive patients. During chronic intravenous infusion of propranolol giving a narrow range of total plasma concentrations (22.5 to 50 ng/ml), there was, at best, a poor correlation with effects. On the other hand, there was excellent correlation between efficacy and free drug concentration, which fitted the predictions of the receptor theory of competitive antagonism. The true affinity constant for the binding of propranolol to its receptor can be calculated in terms of free drug concentration (KAfree) and was found to vary 2-fold compared to the affinity constant in terms of total plasma concentration (KAtotal) which varied 4-fold, the greater variation being due to plasma binding differences. Compared to normal subjects, KAfree and KAtotal were smaller in hypertensive subjects, implying lesser sensitivity to the drug, and plasma propranolol binding was greater. There was no difference in KAfree between high- and low-renin essential hypertensives, but KAtotal was smaller in the high-renin group due to increased plasma binding which did not reach statistical significance. It is concluded that the effect of propranolol on heart rate is a predictable function of free drug concentration in man and that the contribution of individual variation in receptor sensitivity to differences in oral dosage requirement is minor compared to that of variations in bioavailability.
TL;DR: The findings suggest that in the presence of normal vasculature and pulmonary function, Intralipid-induced lipemia should cause no clinical consequences, however, patients with preexisting pulmonary or vascular disease may be at greater risk after IntralIPid- induced lipemia.
TL;DR: The representation of sound frequency within auditory cortex has been investigated with microelectrode mapping techniques in grey squirrels and there is significant variation in the location of the primary field and in the orientation of the frequency representation within it.
Abstract: The representation of sound frequency within auditory cortex has been investigated with microelectrode mapping techniques in grey squirrels. The cyto- and myeloarchitecture of mapped cortical surfaces was examined and related to recording data. Among the results were the following: (1) A primary field can be defined on the basis of both physiological and anatomical criteria. It occupies nearly half of the auditory responsive area in the squirrel. (2) The best frequency of neurons is relatively constant within vertical penetrations across the active middle cortical layer(s) of the primary field. (3) Best frequencies ranging from 190 Hz to 33 kHz were defined within the primary field. There is an orderly representation of sound frequency (and of the cochlear partition) within the field, with lowest frequencies represented rostrally and highest frequencies represented caudally. A given frequency band (sector of the basilar partition) is represented across a roughly straight belt of cortex of approximately constant width that crosses the mediol-lateral dimension of the primary field. There is a proportionately greater surface area of representation of higher frequency octaves within the field. (4) In different squirrels, there is significant variation in the location of the primary field and in the orientation of the frequency representation within it. (5) Auditory responses were recorded within at least two secondary auditory fields. The total region responsive to tonal stimulation approximately corresponded with the anterior temporal field, as defined by Kaas et al. ('72).
TL;DR: In this paper, the autonomous nonlinear functional differential equation x(t) = F(xt), t ⩾ 0, x0 = φ is studied as a semigroup of nonlinear operators in Lp function spaces.
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TL;DR: This behavioral test of falcon acuity supports the common belief that Falconiformès have superb vision, although Falcon acuity was much more dependent on lumanance, declining sharply with decreases in luminance.
Abstract: Grating acuity, the ability to resolve high-contrast square-wave gratings, was measured in a falcon and in humans under comparable conditions. This behavioral test of falcon acuity supports the common belief that Falconiformes have superb vision-the faclon's threshold was 160 cycles per degree, while the human thresholds were 60 cycles per degree. Falcon acuity, however, was much more dependent on lumanance, declining sharply with decreases in luminance.
TL;DR: The addition of physiological concentrations of mEGF to quiescent cultures preincubated in the absence of serum was found to elicit an increased incorporation of 3H‐glucosamine into the glycosaminoglycans and glycoproteins of both the cellular and extracellular fractions.
Abstract: The effect of mouse epidermal growth factor (mEGF) on the synthesis of glycosaminoglycans and glycoproteins by human fibroblasts has been studied The addition of physiological concentrations (10(-9)M) of mEGF to quiescent cultures preincubated in the absence of serum was found to elicit an increased incorporation of 3H-glucosamine into the glycosaminoglycans and glycoproteins of both the cellular and extracellular fractions Although the growth response to the factor, as measured by DNA replication, was minimal under these conditions as compared with the effect of serum, the mEGF-induced incorporation of glucosamine into these cellular constituents and into the extracellular glycoproteins was comparable to that elicited by serum shift-up Serum, however, caused a significantly larger incorporation of glucoasimine into extracellular, acid-soluble glycosaminoglycans, which were shown to contain hyaluronic acid as the major component As previously demonstrated, the growth response to mEGF can be enhanced several fold by an mEGF-binding arginine esterase, which is normally associated with the factor in vivo, and by ascorbate The esterase was found to increase markedly the mEGF-induced incorporation of glucosamine into extracellular hyaluronic acid, while the addition of ascorbic acid did not significantly alter glucosamine incorporation
TL;DR: It has been shown that some drugs exhibit a lower plasma level/dose ratio in infancy and early childhood as compared with the adult, including phenobarbitone, phenytoin and ethosuximide.
Abstract: Wide variations in drug dose recommendations for children of the same or different ages reflect the inadequacy of data on pharmacokinetics and pharmacodynamics in children. Selected aspects of available literature on pharmacokinetics of drugs used in older infants and children has been reviewed with special attention to calculation of an age-appropriate dose. During the neonatal period and early infancy the elimination of many drugs that are excreted in the urine in unchanged form is restricted by the immaturity of glomerular filtration and renal tubular secretion. On the other hand, in late infancy and/or in childhood, a similar or greater rate of elimination from plasma than in adults has been observed for many drugs, notably digoxin, phenobarbitone, phenytoin, carbamazepine, ethosuximide, diazoxide, clindamycin and propoxyphene. Consistent with this, it has been shown that some drugs exhibit a lower plasma level/dose ratio in infancy and early childhood as compared with the adult. This is true for phenobarbitone, phenytoin and ethosuximide. Some age groups of children remain uninvestigated with regard to pharmacokinetics, even for the drugs reviewed. Therefore, pediatric therapy remains empirically based for many drugs.
TL;DR: In this article, the behavior of bolted end plates for moment-resistant connections between steel structural members was investigated using 2-D and 3-D finite element analysis, where the analysis was based on the constant strain triangle and an eight-noded subparametric brick element.