‘The National Socialist rulers of Germany invented new ways of controlling the policy and action ... more ‘The National Socialist rulers of Germany invented new ways of controlling the policy and action of other countries without subjecting them to a formal military occupation, and some day it may be necessary for our courts to consider whether conduct equivalent to the German practice of establishing complete and effective domination over professedly neutral countries by insinuating agents and specialist troops into key positions, while permitting their governments nominally to continue to exercise their functions, as a prelude to plunging them into war, amounts to enemy occupation or not’
The response of a barotropic coastal ocean on a step-shaped continental shelf to a traveling sinu... more The response of a barotropic coastal ocean on a step-shaped continental shelf to a traveling sinusoidal wind stress forcing is predicted theoretically using a frictional force proportional to the alongshore current velocity. This theory is compared to a small set of observations ...
AimsA common, functionally significant polymorphism in GRK5 (Gln41Leu) encodes a gain-of-function... more AimsA common, functionally significant polymorphism in GRK5 (Gln41Leu) encodes a gain-of-function enzyme that enhances desensitization of the β1-adrenergic receptor. GRK5 Leu41 has been postulated to confer endogenous ‘genetic β-blockade’ and contribute to an attenuated response to β-blockers in black subjects. The effects of this GRK5 variant on sensitivity to a β-blocker have not been studied in humans. We hypothesized that the GRK5 Gln41Leu variant contributes to interindividual variability in response to β-blockade and to the ethnic difference in sensitivity between black and Caucasian individuals.Materials & methodsWe measured the heart rate at rest and during a graded incremental exercise in 154 healthy subjects (85 white and 69 black) before and after an oral administration of 25 mg atenolol. We determined the genotypes of GRK5 (Gln41Leu), β1-adrenergic receptor (ADRB1 Ser49Gly and Arg389Gly) genotypes and plasma atenolol concentrations. The effects of genotype and covariates on sensitivity to atenolol, measured as the reduction in exercise-induced tachycardia, were determined using multiple regression analyses.ResultsThe minor allele frequency of GRK5 Leu41 was 32.6% in blacks and 0% in whites. Black individuals were less sensitive to atenolol than white individuals (p ≤ 0.011) but this was not explained by the GRK5 genotype. The GRK5 genotype had no effect on resting heart rate before (p = 0.61) and after adjustment for age, sex, ethnicity, atenolol concentrations, BMI and ADRB1 genotypes (p = 0.81). The decrease in heart rate after atenolol administration did not differ significantly according to the GRK5 genotype at rest or after exercise, before (all p > 0.14) and after statistical adjustment for covariates (all p > 0.17).ConclusionThe GRK5 Gln41Leu polymorphism does not affect sensitivity to the β1-adrenergic blocker, atenolol, during acute physiological adrenergic stimulation, nor does it contribute to the ethnic differences in sensitivity to atenolol among black and Caucasian individuals.
Allogeneic reactions have conventionally been considered as typical immune responses by one popul... more Allogeneic reactions have conventionally been considered as typical immune responses by one population of cells to antigens present on the other. This view is inadequate, since it does not explain many features of these reactions, among which are: (1) reactivity is much ...
ABSTRACT This paper proposes that most antibody diversity arises by rapid production of variants ... more ABSTRACT This paper proposes that most antibody diversity arises by rapid production of variants within clones of antibody-forming cells after antigenic or mitogenic stimulation. Evidence for this comes from cloning experiments in vivo and in vitro , including micromanipulative work where single antibody-forming cells were cultured for 2 days and their progeny shown to be heterogeneous for antibody specificity in some cases.
The technique of adoptively transferring an immune response by injecting donor cells into irradia... more The technique of adoptively transferring an immune response by injecting donor cells into irradiated recipient mice is based on the assumption that the host is rendered immunologically inert by irradiation. We present evidence that these mice are not inert; in the presence of donor cells of various types they mount a substantial immune response against both heterologous erythrocytes and dinitrophenylated bovine serum albumin. This restoration of the host requires donor cells for its expression and can account for up to 100% of the total response. The problems associated with this finding are discussed.
We formulate a variant of the "double Monod model" which takes explicit account... more We formulate a variant of the "double Monod model" which takes explicit account of endogenous metabolism. Using parameter values appropriate to carbohydrate-limited substrate, bacterial prey, and protozoan predator, we study the stability of steady states under chemostat conditions. We conclude that the predator's endogenous metabolism may have a stabilizing effect at low dilution rates.
... Received 23 August 1978; revised 24 September 1979. Available online 17 February 2007. The gr... more ... Received 23 August 1978; revised 24 September 1979. Available online 17 February 2007. The growth of single-nutrient limited algal cultures has been independentlydescribed by several authors in terms of the same basic mathematical model. ...
‘The National Socialist rulers of Germany invented new ways of controlling the policy and action ... more ‘The National Socialist rulers of Germany invented new ways of controlling the policy and action of other countries without subjecting them to a formal military occupation, and some day it may be necessary for our courts to consider whether conduct equivalent to the German practice of establishing complete and effective domination over professedly neutral countries by insinuating agents and specialist troops into key positions, while permitting their governments nominally to continue to exercise their functions, as a prelude to plunging them into war, amounts to enemy occupation or not’
The response of a barotropic coastal ocean on a step-shaped continental shelf to a traveling sinu... more The response of a barotropic coastal ocean on a step-shaped continental shelf to a traveling sinusoidal wind stress forcing is predicted theoretically using a frictional force proportional to the alongshore current velocity. This theory is compared to a small set of observations ...
AimsA common, functionally significant polymorphism in GRK5 (Gln41Leu) encodes a gain-of-function... more AimsA common, functionally significant polymorphism in GRK5 (Gln41Leu) encodes a gain-of-function enzyme that enhances desensitization of the β1-adrenergic receptor. GRK5 Leu41 has been postulated to confer endogenous ‘genetic β-blockade’ and contribute to an attenuated response to β-blockers in black subjects. The effects of this GRK5 variant on sensitivity to a β-blocker have not been studied in humans. We hypothesized that the GRK5 Gln41Leu variant contributes to interindividual variability in response to β-blockade and to the ethnic difference in sensitivity between black and Caucasian individuals.Materials & methodsWe measured the heart rate at rest and during a graded incremental exercise in 154 healthy subjects (85 white and 69 black) before and after an oral administration of 25 mg atenolol. We determined the genotypes of GRK5 (Gln41Leu), β1-adrenergic receptor (ADRB1 Ser49Gly and Arg389Gly) genotypes and plasma atenolol concentrations. The effects of genotype and covariates on sensitivity to atenolol, measured as the reduction in exercise-induced tachycardia, were determined using multiple regression analyses.ResultsThe minor allele frequency of GRK5 Leu41 was 32.6% in blacks and 0% in whites. Black individuals were less sensitive to atenolol than white individuals (p ≤ 0.011) but this was not explained by the GRK5 genotype. The GRK5 genotype had no effect on resting heart rate before (p = 0.61) and after adjustment for age, sex, ethnicity, atenolol concentrations, BMI and ADRB1 genotypes (p = 0.81). The decrease in heart rate after atenolol administration did not differ significantly according to the GRK5 genotype at rest or after exercise, before (all p > 0.14) and after statistical adjustment for covariates (all p > 0.17).ConclusionThe GRK5 Gln41Leu polymorphism does not affect sensitivity to the β1-adrenergic blocker, atenolol, during acute physiological adrenergic stimulation, nor does it contribute to the ethnic differences in sensitivity to atenolol among black and Caucasian individuals.
Allogeneic reactions have conventionally been considered as typical immune responses by one popul... more Allogeneic reactions have conventionally been considered as typical immune responses by one population of cells to antigens present on the other. This view is inadequate, since it does not explain many features of these reactions, among which are: (1) reactivity is much ...
ABSTRACT This paper proposes that most antibody diversity arises by rapid production of variants ... more ABSTRACT This paper proposes that most antibody diversity arises by rapid production of variants within clones of antibody-forming cells after antigenic or mitogenic stimulation. Evidence for this comes from cloning experiments in vivo and in vitro , including micromanipulative work where single antibody-forming cells were cultured for 2 days and their progeny shown to be heterogeneous for antibody specificity in some cases.
The technique of adoptively transferring an immune response by injecting donor cells into irradia... more The technique of adoptively transferring an immune response by injecting donor cells into irradiated recipient mice is based on the assumption that the host is rendered immunologically inert by irradiation. We present evidence that these mice are not inert; in the presence of donor cells of various types they mount a substantial immune response against both heterologous erythrocytes and dinitrophenylated bovine serum albumin. This restoration of the host requires donor cells for its expression and can account for up to 100% of the total response. The problems associated with this finding are discussed.
We formulate a variant of the "double Monod model" which takes explicit account... more We formulate a variant of the "double Monod model" which takes explicit account of endogenous metabolism. Using parameter values appropriate to carbohydrate-limited substrate, bacterial prey, and protozoan predator, we study the stability of steady states under chemostat conditions. We conclude that the predator's endogenous metabolism may have a stabilizing effect at low dilution rates.
... Received 23 August 1978; revised 24 September 1979. Available online 17 February 2007. The gr... more ... Received 23 August 1978; revised 24 September 1979. Available online 17 February 2007. The growth of single-nutrient limited algal cultures has been independentlydescribed by several authors in terms of the same basic mathematical model. ...
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