David A. Juckett

Solar activity cycles, north/south asymmetries, and differential rotation associated with solar spin-orbit variations

The possible role of the Suns planetary-induced spin-orbit dynamics in the generation of various solar oscillations is examined using simple approaches and heuristic models. Theoretically, the 22.5-yr dipole inversion magnetic cycle and the recently described 17-yr neutral line topology cycle can be derived from the non-linear mixing of two oscillations with periods of approximately 20 and 165 years. Oscillations with such periods are observed in two aspects of the Suns spin-orbit dynamics. The 20-yr oscillation is the fundamental variation in the angular momentum of the solar body with respect to the solar system center-of-mass, while the 165-yr oscillation is the lowest-frequency component of the spin projection variations. It is shown that these two oscillations when mixed non-linearly yield, to a 1st-order approximation, the correct phase and frequency of the observed 17.5- and 22.5-yr magnetic cycles. By allowing an asymmetric shape to the 165-yr oscillation, the frequency modulation inherent in the Hale cycle (and sunspot cycle) is reproduced, yielding a more accurate estimate of solar activity. The asymmetric 165-yr oscillation matches the combination of the two lowest frequency components (165- and 84-yr periods) of the spin projection variations. Hemispheric sunspot asymmetry cycles, north/south differences in convective zone rotational velocities, and meridional flows are also shown to be expected byproducts of classical spin-orbit effects. Finally, the problem of low activity epochs (e.g., Maunder minimum) can be seen as a natural outcome of the interactions among the driving and driven oscillations involved in the conservation of solar system angular momentum.

Protein from intestinal Eimeria protozoan stimulates IL‐12 release from dendritic cells, exhibits antitumor properties in vivo and is correlated with low intestinal tumorigenicity

The small intestine (SI) of vertebrates exhibits low tumorigenesis and rarely supports metastatic growth from distant tumors. Many theories have been proposed to address this phenomenon, but none has been consistently supported. One candidate mechanism is that the vast immunologic compartment of the SI provides a heightened level of tumor immunosurveillance. Consistent with this, we have identified a molecule of low abundance from bovine SI that has the hallmarks of a potent immunostimulant and may be associated with the natural suppression of cancer in the intestinal tract. The protein originates from an endemic gut protozoan, Eimeria spp., and is homologous to the antigen 3‐1E previously isolated from the avian apicomplexan E. acervulina. We show here that it is a very potent stimulator of IL‐12 release from dendritic cells, upregulates inflammatory modulators in vivo (IL‐12, MCP‐1, IL‐6, TNF‐α and INF‐γ) and has antitumor properties in mice. In addition, it is synergistic in vitro with anti‐CD40 antibody, IFN‐γ, IL‐4 and GM‐CSF; is active across species barriers in vivo; and has no observable toxicity. Based on these activities, we speculate that it is an inducer of protozoan‐targeted innate immunity, which may explain its potential benefit to the intestinal tract and potency as an agent in cancer immunotherapy.

Correlation of Human Longevity Oscillations with Sunspot Cycles

An examination of past human mortality trends revealed that the mean longevity of birth cohorts from 1740 to 1900 for United States of America (U.S.) Congressional Representatives exhibited oscillations that coincided with the 9- to 12-year sunspot cycle. Cohort mean longevities were 2-3 years greater during times of low sunspot activity than at peak activity. This phenomenon was confirmed in data from members of the House of Commons of the United Kingdom Parliament and from University of Cambridge alumni. An additional longevity oscillation with a longer period was visible in the data and may also be related to sunspot cycles. The amplitude and frequency modulations in the longevity and sunspot oscillations aligned when a 20-year phase shift was incorporated. This shift requires the existence of a lag between solar changes and the affected birth cohorts. Several possible causes of the effect are discussed, in particular: radiation on primordial germ cells in developing embryos; influenza epidemics and pandemics; and weather. The size of the longevity oscillation requires that the solar effect must be considered in studies that examine longevity trends and risk estimation.

Periodic clustering of human disease-specific mortality distributions by shape and time position, and a new integer-based law of mortality

Abstract Human mortality distributions were analyzed for 29 disease-specific causes-of-death in male and female, White (U.S.A.), Black (U.S.A.) and Japanese (Japan) populations, constituting a total of 162 separate cohorts. For each cohort distribution, the curve moments and the parameters values for fits to model equations were determined. The differences between cohort distributions were characterized by two degrees of freedom, related to distribution position and shape, respectively. A form of the Weibull function was shown to contain two parameters that mapped to these two degrees of freedom. Parametric analysis on 136 best-fitting cohorts yielded periodic clustering in the set of values for both Weibull parameters as quantitated using a Fourier transform method and an independent statistical method. This periodicity was unlikely to have occurred by change ( P

Correlation of a 140-year global time signature in cancer mortality birth cohorts with galactic cosmic ray variation

An understanding of the cosmic ray modulation of life processes is critical to space exploration, evolution and current medical science. Previous evidence has implicated a role for cosmic rays in US female cancer, involving a possible cross-generational foetal effect. This study explores the global nature of that effect by examining cancer time variations for population cohorts in five countries on three continents. Age–period–cohort analysis was used to separate cohort-related effects from period-related effects, generating time signatures for comparisons among both male and female populations in the United States (US), United Kingdom (UK), Australia (AU), Canada (CA) and New Zealand (NZ). The available cancer mortality data spanned most of the 20th century for US, UK and AU, with shorter periods for CA and NZ. The longest cohort series spanned 1825 to 1965 and exhibited two peaks of higher mortality likelihood approximately 75 years apart in all countries and in both sexes. The constancy of this oscillation on three continents and both hemispheres suggests the presence of a global environmental effect. To explore a possible source for this effect, the birth cohort oscillation is shown to correlate with the variations in background cosmic radiation one generation prior to the birth cohorts. This confirms an earlier study correlating human breast cancer mortality and galactic cosmic rays. A corroborating correlation is also noted between the latitude dependences of cancer incidence in 42 countries and the intensity of background cosmic rays. The role of germ cells as a possible target of this radiation is discussed, emphasizing the amplification that must occur to make this weak radiation relevant to human health. Germ cell timing for this effect has profound implications for evolution, long-distance space travel and the colonization of planets with high background radiation.

Cellular aging (The hayflick limit) and species longevity: A unification model based on clonal succession

A model is presented which proposes a specific cause-and-effect relationship between a limited cell division potential and the maximum lifespan of humans and other mammals. It is based on the clonal succession hypothesis of Kay which states that continually replicating cell beds (e.g. bone marrow, intestinal crypts, epidermis) could be composed of cells with short, well-defined division potentials. In this model, the cells of these beds are proposed to exist in an ordered hierarchy which establishes a specific sequence for cell divisions throughout the organisms lifespan. The depletion of division potential at all hierarchical levels leads to a loss of bed function and sets an intrinsic limit to species longevity. A specific hierarchy for cell proliferation is defined which allows the calculation of time to bed depletion and, ultimately, to organism mortality. The model allows the existence of a small number (n) of critical cell beds within the organism and defines organism death as the inability of any one of these beds to produce cells. The model is consistent with all major observations related to cellular and organismic aging. In particular, it links the PDLs (population doubling limit) observed for various species to their mean lifespan; it explains the slow decline in PDL as a function of age of the donor; it establishes a thermodynamically stable maximum lifespan for a disease-free population; and it can explain why tissue transplants outlive donors or hosts.

A method for determining the number of documents needed for a gold standard corpus

The unstructured narratives in medicine have been increasingly targeted for content extraction using the techniques of natural language processing (NLP). In most cases, these efforts are facilitated by creating a manually annotated set of narratives containing the ground truth; commonly referred to as a gold standard corpus. This corpus is used for modeling, fine-tuning, and testing NLP software as well as providing the basis for training in machine learning. Determining the number of annotated documents (size) for this corpus is important, but rarely described; rather, the factors of cost and time appear to dominate decision-making about corpus size. In this report, a method is outlined to determine gold standard size based on the capture probabilities for the unique words within a target corpus. To demonstrate this method, a corpus of dictation letters from the Michigan Pain Consultant (MPC) clinics for pain management are described and analyzed. A well-formed working corpus of 10,000 dictations was first constructed to provide a representative subset of the total, with no more than one dictation letter per patient. Each dictation was divided into words and common words were removed. The Poisson function was used to determine probabilities of word capture within samples taken from the working corpus, and then integrated over word length to give a single capture probability as a function of sample size. For these MPC dictations, a sample size of 500 documents is predicted to give a capture probability of approximately 0.95. Continuing the demonstration of sample selection, a provisional gold standard corpus of 500 documents was selected and examined for its similarity to the MPC structured coding and demographic data available for each patient. It is shown that a representative sample, of justifiable size, can be selected for use as a gold standard.

Integral differences among human survival distributions as a function of disease

The mortality kinetics of white humans of the United States were examined for 25 different age-related causes of death (22 male, 21 female). The survivorship distributions for these diseases clustered into groups, as defined by their position on the time axis. When the survivorship curves were linearized, by plotting as log(-log S(t] vs. log t, this clustering was easily identified as well-defined intersections among the lines separated by 2-year intervals. The four largest groups had intersections at approximate time values of 101, 99, 95, and 93 years, with a small group having an intersection at 97 years. The distribution of diseases among the intersections was not random but was related to sex and disease type. The two-parameter Weibull and GDCP (Gamma Distribution raised to a Combinatoric Power) functions were fit to the individual cause of death survivorship curves and yielded parametric values for the shape (slope) and median time to death. These two parameters varied with disease type and exhibited a positive, linear regression. The regression slope between the shape (alpha) and time (tau m) parameters of the GDCP was also equal to approximately 2 years. This suggested to us that the 2-year intervals in the median times of death with integral changes in the shape parameter and the 2-year time interval between the survivorship clusters may both arise from a similar process involving integral numbers of discrete steps.

The kinetics and thermodynamics of lysis of young and old sheep red blood cells.

The kinetics of heat-induced lysis of a population of sheep red blood cells over the temperature range 42 degrees - 56 degrees C are shown to be similar in form to the survivorship curves of multicellular organisms and are describable by the power law function,--(1/N)(dN/dt) = At(n-1). The A parameter of the power law function is examined in this model system in an attempt to show its relationship to molecular events. Arrhenius-type plots of the A parameter are different for old populations of red blood cells compared to young populations. The plot for the old cells shows a high energy transition at 50 degrees C. For the young cells an activation enthalpy of 232 kcal/mole is obtained with no transition occurring at 50 degrees C. The parameter l/tau, defined as A1/n, is more directly related to the molecular basis of the temperature dependence of the lysis kinetics. The Arrhenius plots of 1/tau give activation enthalpies of 42.8 and 40.4 kcal/mole for young and old cells, respectively, and activation entropies of 57.6 and 50.3 cal/mole per degree. These activation enthalpies and activation entropies appear to be in accord with a compensation law for these qualities for protein denaturation, and support the suggestion that protein denaturation is the rate-limiting step in the lysis of sheep red blood cells.

Intestinal protozoa are hypothesized to stimulate immunosurveillance against colon cancer

Colon cancer in humans results in considerable morbidity and mortality throughout most of the world. During the twentieth century, there was a rapid rise in colon cancer within modernizing countries that has not been adequately explained, although the role of diet has been widely explored. Previously, we showed that the presence of the endemic Eimeria spp. protozoan in intestinal tissues is associated with regions of low tumorigenesis in the large and small bovine intestine and that an Eimeria surface protein is a potent activator of dendritic cells and a useful immunomodulator, with anti-cancer and anti-viral properties. Therefore, we hypothesize that the persistent presence of such an intestinal protozoan enhances immunosurveillance by elevating the intestinal alert status and that the loss of these organisms could lead to a higher incidence of colon cancer. Preliminary support of this hypothesis derives from the observations that domestic animals, known to maintain this protozoan, have very low colon cancer incidence. We propose that this also may occur in human populations that use human excrement (night soil) as a fertilizer, a practice that serves to complete the life cycle of this type of microbe. We examine some evidence for this hypothesis in Japans mortality patterns, where we show that colon cancer increased after the cessation of night soil use, but before the change to a western diet. We conclude that this hypothesis, a variation of the hygiene hypothesis, is worth further consideration and continued elaboration.