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A recombinant Eimeria protozoan protein antigen (rEA) has been shown to have antitumor and antiviral activity. The purpose of this study was to determine the effect of rEA treatment alone or in combination with an agonist cocktail consisting of granulocyte macrophage colony stimulating factor (GM-CSF), interferon gamma (IFN-γ), interleukin 4 (IL-4), and anti CD-40 antibody, in the treatment of Banzi virus (BV) disease in BALB/c mice. Treatment with rEA resulted in a significant increase in survival, weight gain, and mean day to death in BV-infected mice and resulted in a significant decrease in brain virus titer. Treatment with rEA, in combination with a 4-agonist cocktail, improved disease parameters to a greater degree than rEA treatment alone. The effect of treatment with a reduced concentration of agonist cocktail or fewer components of the agonist cocktail, in combination with rEA, on disease outcome in BV-infected mice was also investigated. Treatment with rEA, alone or in combination with agonist cocktail, 24 hours after virus challenge did not improve disease. Treatment with rEA, alone or in combination with an agonist cocktail, is efficacious for the prophylaxis of BV infection in mice.

The distributions for human disease-specific mortality exhibit two striking characteristics: survivorship curves that intersect near the longevity limit; and, the clustering of best-fitting Weibull shape parameter values into groups centered on integers. Correspondingly, we have hypothesized that the distribution intersections result from either competitive processes or population partitioning and the integral clustering in the shape parameter results from the occurrence of a small number of rare, rate-limiting events in disease progression. In this report we initiate a theoretical examination of these questions by exploring serial chain model dynamics and parameteric competing risks theory. The links in our chain models are composed of more than one bond, where the number of bonds in a link are denoted the link size and are the number of events necessary to break the link and, hence, the chain. We explored chains with all links of the same size or with segments of the chain composed of different size links (competition). Simulations showed that chain breakage dynamics depended on the weakest-link principle and followed kinetics of extreme-values which were very similar to human mortality kinetics. In particular, failure distributions for simple chains were Weibull-type extreme-value distributions with shape parameter values that were identifiable with the integral link size in the limit of infinite chain length. Furthermore, for chains composed of several segments of differing link size, the survival distributions for the various segments converged at a point in the S(t) tails indistinguishable from human data. This was also predicted by parameteric competing risks theory using Weibull underlying distributions. In both the competitive chain simulations and the parametric competing risks theory, however, the shape values for the intersecting distributions deviated from the integer values typical of human data. We conclude that rare events can be the source of integral shapes in human mortality, that convergence is a salient feature of multiple endpoints, but that pure competition may not be the best explanation for the exact type of convergence observable in human mortality. Finally, while the chain models were not motivated by any specific biological structures, interesting biological correlates to them may be useful in gerontological research.

Toll-like receptor (TLR) ligands are attractive adjuvant candidates in vaccine development. Eimeria tenella profilin-like protein has recently been shown to be a potent agonist of the innate immune system through its recognition by Toll-like receptor-11. In this report, we studied the systemic and mucosal adjuvant activity of Eimeria profilin-like protein within a vaccinal strategy against Toxoplasma gondii in mice. Using intraperitoneal (i.p.) immunization, we observed that coadministration of the recombinant Eimeria antigen (rEA) with T. gondii antigen (TAg) effectively elevates plasma levels of IL-12p70 and consequently induced both enhanced specific humoral and Th1 cellular immune responses. The co-administration of TAg plus rEA by i.p route significantly enhanced the protection against T. gondii infection (62% brain cyst reduction) in comparison with control mice and with mice immunized with TAg alone (only 36% brain cyst reduction). After intranasal immunization, humoral and cellular responses were weak. However mice immunized nasally with TAg plus rEA were significantly protected with 50% of brain cyst reduction, conversely TAg immunized mice did not present any brain cyst reduction.These results indicate that Eimeria profilin-like protein would serve as an efficacious systemic and mucosal adjuvant inducing protective immune response against chronical stage of T. gondii infection through TLR11 activation.

A periodic pattern was discovered among the relative number of deaths per year for the major age-related diseases in humans. This pattern was observed among 178 causes-of-death composed of male and female. White (U.S.A.), Black (U.S.A.) and Japanese (Japan) populations. Both descriptive (Fourier transform) and statistical analysis procedures revealed evidence that the pattern resulted from the presence of an underlying power progression between disease prevalences, with a factor of approximately 2.0 between sizes. This periodicity was highly unlikely to have occurred by chance (P much less than 0.01). The presence of such a power progression suggests that the sizes of the various fractions of the total population, that are afflicted with these mortal diseases, are determined by forces intrinsic to the population and probably result from a common mechanism.

Recombinant Eimeria antigen (rEA) has been shown to have potent anticancer and antiviral activity in respective mouse disease models, presumably through robust immune stimulation that occurs via TLR11, a pattern recognition receptor that recognizes profilin-like proteins expressed on apicomplexan protozoans. Comparable immunostimulatory activity in other species has yet to be demonstrated. Since rEA is known to be highly effective in treating Punta Toro virus (PTV) infection in mice, its ability to elicit protective immunity in the hamster PTV infection model was investigated. rEA was given alone, or in combination with IL-18 or IL-2, and virally challenged hamsters were observed for mortality. Cytokine transcript profiles for IL-12p40, IL-21, IFN-gamma and TNF-alpha were assessed to evaluate the induction of these inflammatory mediators known to be induced in mice following exposure to rEA. A dose of 100 microg of rEA, given once 4 h prior to viral challenge, and a second time on day 3 of the infection, was found to be the most effective prophylactic therapy protecting 60% of treated hamsters from mortality, compared to only 5-10% observed in animals receiving placebo. Increased expression of IFN-gamma and IL-12p40 was evident following treatment with rEA. The data suggest that rEA does induce host antiviral responses in hamsters that result in significant protection from death, although determining the most appropriate dose for intervention in other species, including humans, will likely be challenging.

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 parameter 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 chance (P less than 0.01). We have combined these results into a Law of Mortality, based on a Weibull function containing only integer parameters and constants, which is valid for all human age-related disease mortality. We show that the life expectancy differences between races and sexes is completely described by this formalism. We conclude that human mortality is controlled by discrete events, which are manifested in the appearance of only allowed mortality curve shapes and positions.

A protein antigen from an Eimeria protozoan has recently been reported to induce antitumor activity in mice. This activity most likely results from the strong induction of interkeukin-12 (IL-12) and gamma interferon (IFN-γ), which are also essential factors in the establishment of protective immunity against viral infection. We evaluated recombinant Eimeria antigen (rEA) as a potential immunotherapeutic agent in mouse and hamster models of acute phleboviral disease. Punta Toro virus (PTV) was highly sensitive to a single dose of nanogram quantities of rEA in the mouse infection model. Intraperitoneal treatment with rEA also reduced virus load and liver damage associated with PTV infection. IL-12 was elicited following exposure of uninfected mice to quantities of rEA of 10 ng or greater, and the levels peaked at between 3 and 8 h postexposure. IFN-γ release was induced more slowly and required less rEA (1 ng) to produce a significant rise in systemic levels. The induction of IL-12 and IFN-γ involved in the coordination of innate and adaptive immune responses to microbial pathogens required myeloid differentiation factor 88, a signaling adaptor shared by most members of the Toll-like receptor (TLR) family. Despite encouraging results in the murine system, rEA failed to protect hamsters challenged with PTV. Our findings suggest that hamsters may lack functional TLR11, which has recently been shown to recognize a profilin-like protein homologous to rEA from the protozoan Toxoplasma gondii . Further investigation into the immunostimulatory capacity of rEA in other mammalian systems is necessary.

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-alpha and INF-gamma) and has antitumor properties in mice. In addition, it is synergistic in vitro with anti-CD40 antibody, IFN-gamma, 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.

Techniques from cancer epidemiology and time series analysis were used to explore the hypothesis that cosmic radiation can induce germ cell changes leading to increases in future breast cancer mortality. A birth cohort time series for female breast cancer mortality was obtained using a model-independent, age-period-cohort analysis on age-specific mortality data for 1940–1990. The birth cohort series contained several oscillatory components, which were isolated and compared to the corresponding frequency components of a cosmic ray surrogate time series – Greenland ice-core 10Be concentrations. A technique, referred to as component wave-train alignment, was used to show that the breast cancer and cosmic ray oscillations were phase-locked approx. 25 years before the time of birth. This is consistent with the time of germ cell formation, which occurs during the fetal development stage of the preceding generation. Evidence is presented that the observable oscillations in the birth cohort series were residues of oscillations of much larger amplitude in the germ cell cohort, which were attenuated by the effect of the broad maternal age distribution. It is predicted that a minimum of 50% of breast cancer risk is associated with germ cell damage by cosmic radiation (priming event), which leads to the development of individuals with a higher risk of breast cancer. It is proposed that the priming event, by preceding other steps of carcinogenesis, works in concert with risk factor exposure during life. The priming event is consistent with epigenetic changes such as imprinting.

The Gompertz and Weibull functions are compared with respect to goodness-of-fit to human mortality distributions; ability to describe mortality curve intersections; and, parameter interpretation. The Gompertz function is shown to be a better descriptor for 'all-causes' of deaths and combined disease categories while the Weibull function is shown to be a better descriptor of purer, single causes-of-death. A modified form of the Weibull function maps directly to the inherent degrees of freedom of human mortality distributions while the Gompertz function does not. Intersections in the old-age tails of mortality are explored in the context of both functions and, in particular, the relationship between distribution intersections, and the Gompertz ln[R0] versus alpha regression is examined. Evidence is also presented that mortality intersections are fundamental to the survivorship form and not the rate (hazard) form. Finally, comparisons are made to the parameter estimates in recent longitudinal Gompertzian analyses and the probable errors in those analyses are discussed.

The dying off of human population cohorts due to different age related diseases rigorously follows stochastically derived rules. The existence of such rules suggests a common, fundamental mechanism for human mortality. We show here, by a simple quantitative analysis, that the progressive loss with age of genetic triplet code information (anticodons) in body cells, as described by the statistics of extremes in order theory, serves as such a mechanism.

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.

The synthesis and /sup 195/Pt chemical shifts of the hydroxo-bridged dimer and trimer, isolated form an aquated solution of bis(nitrato)(trans-1,2-diaminocyclohexane)platinum (I), at different pH are described. The chemical shifts of these three complexes are widely separated, and /sup 195/Pt NMR provides a convenient method for the investigation of dimer formation kinetics from I. Rate constants for the dimerization reaction calculated at different pD, temperature, and concentration agree well with the hypothesis that dimerization occurs with a rate-limiting bimolecular reaction of an intermediate hydroxo species formed by the loss of a proton from the parent complex.

Any thermodynamic study of aging and death in laboratory mammals is dependent on techniques which would allow for the chronic manipulation of the core body temperature of these organisms. Accordingly, the hypothermic response after parenteral administration of chlorpromazine, L-dopa, reserpine, and p -chlorophenylalanine was investigated in the mouse. Mice injected at 24 hour intervals with chlorpromazine exhibited a diminished response (tolerance) with repeated administration. The degree of induced hypothermia and resistance to tolerance was greater in male mice than in female mice. L-dopa was unable to potentiate chlorpromazine hypothermia but did evoke a non-adapting hypothermic response when administered alone. Reserpine also evoked a non-adapting hypothermia. Further, animals treated with small doses of reserpine exhibited an increasing response with repeated injections. p -Chlorophenylalanine induced hypothermy that became intermittent with successive administration. The results presented here indicate that both reserpine and L-dopa would be of value as hypothermic agents in long term investigations.

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 (α) and time (τm) 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.

Treatment of mixtures of cis and trans Pt(NH3)2Cl2 with thiourea (thu) gave Pt(thu)4Cl2 and trans [Pt(NH3)2(thu)2]Cl2 which were separated and quantified by high-performance liquid chromatography using a strong cation exchange column. Several platinum-thiourea compounds have been studied by NMR (1H, 13C, 195Pt), an increase in the coalescence temperature of the NH2 resonances being observed as a result of co-ordination. The NMR data has also been used to show the presence of interactions between the Pt(thu)2+4 and PtCl2−6 ions of [Pt(thu)4][PtCl6] in dimethylsulphoxide solution.

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.

The preparation of Pt(NH3)2(MeU)2·2H2O, 1. [(NH3)2Pt(MeU)2Pt(NH3)2](NO3)2, 2. Pt(NH3)2Cl(MeU), 3. and (in solution) [Pt(NH3)2(OH)(MeU)], 4. (MeU = 1-methyluracil monoanion) is reported. Levels of l-methyluracil and 1–4 in platinum-l-methyluracil blue (PtMeUB) have been assessed by high performance liquid chromatography (HPLC). This technique has also been used to show that in physiological saline or water, PtMeUB hydrolyzes to 3 or 4, respectively. Visible spectroscopy shows that the rate of hydrolysis of PtMeUB is much faster in fetal calf serum than in saline or water, with HPLC indicating that the product of hydrolysis in serum is 3. The precipitate obtained upon treatment of DNA solutions with PtMeUB has also been shown to hydrolyze to 3 or 4 when suspended in saline or water. Compounds 1–3 have been tested against the Ascites S-180J tumors, with 2 and 3 being active, while 4 has been shown to react readily with DNA. Possible mechanisms of antitumor action of PtMeUB that involve 3 and 4 are proposed.

Some platinum coordination complexes are active anticancer drugs in animal and man. This new class of chemotherapeutics was discovered during the course of investigation of the electric field effect on bacterial growth. The platinum electrodes electrolyzed during the experiment, releasing a platinum complex which caused complete cessation of cell division in the bacterial rods. With this filamentation assay system, we were able to identify the specific chemical as cis-dichlorodiammineplatinum(II), a complex known since 1848. The bacterial studies with many such complexes suggested to us the generalizations that charged platinum complexes were bacteriocidal, while the neutral platinum complexes induced filamentation and, in lysogenic bacteria, lysis. The neutral complexes have ignificant activity against transplantable, virally induced, and chemically induced cancers in animals. They are synergistic with almost every other anticancer drug in current use. In man kidney toxicity is the dose limiting ...

Measurements are reported on some characteristics of photo‐conduction and semiconduction in pure crystalline chlorophylls a and b. The semiconduction activation energy is 1.12 ev in chlorophyll a and 1.44 ev in chlorophyll b (E/2kT). The latter value is in excellent agreement with the triplet state energy of 1.43 ev measured by the phosphorescence method in chlorophyll b. The former value suggests that a possible cause of the lack of detectable phosphorescence in chlorophyll a is that it occurs in the infrared at about 11 000 A. The evidence indicates that the mobility of the predominant charge carriers (positive holes) is the same in both crystals. Photoconduction is easily measured in chlorophyll b and less easily in chlorophyll a, because of the much larger dark current. The photoconduction activation energy in chlorophyll b is 0.36 ev. This supports Rabinowitch's view that photoconduction in chlorophyll is not involved in the primary act of photosynthesis.The oxygen adsorbed on the surface of the crys...

When a solution containing the complex ion, [PtCl6]=, and NH4+ ions is irradiated, a photochemical change occurs in which the chloride ions of the ligand are sequentially replaced by 1, 2, or 3 ammonia molecules. The total charge on the complex ion decreases by 1 negative charge for each replacement. These changes can be followed by changes occurring in absorption spectra or in ionophoretic patterns. Each charged species of the complex has a unique effect on the bacteriological growth of Escherichia coli. The doubly negative species is a bacteriocide. The singly negative species appears to have little effect on either growth or cell division processes. The neutral species has little effect on growth, but markedly inhibits cell division processes, forcing filamentous growth. The cis and trans forms of the diamino complex, [PtCl4(NH3)2]0, have been synthesized. The absorption spectra of both have a λmax at 207 mµ. The electrophoretic patterns indicate predominantly neutral species in both cases. The trans form is relatively inefficient in inhibiting cell division, whereas the cis form is fully as efficient as the neutral species in inhibiting cell division. We identify the neutral species as the cis form of the complex.

Some evidence is presented indicating that the formation of a triplet state is involved as an intermediary step in the creation and transfer of charges in the photoconduction process in organic substances. On the basis of the simple potential curve picture, approximate solutions are obtained to the rate process equations. These equations predict that the density of the triplet states under thermal and optical equilibrium conditions will follow a Boltzmann exponential dependence upon temperature with an energy equal to a low multiple (1 or 2) of the vibrational spacing of the excited singlet state. The assumption is made that the photocurrent is proportional to the triplet state density. Measurements by the author and others of the photoconduction activation energy in a number of aromatic hydrocarbons are in very good agreement with this. The triplet state model also requires that the buildup and decay of the photocurrents be approximately monomolecular with time constants at low temperatures and intensiti...

Experimental data on semiconducting organic substances are usually processed by use of the two‐constant equation, σ(T) = σ0exp(−E / 2kT). Evidence from a number of cases now indicates that σ0 is dependent on E, when the equation is applied to certain single substances where E varies with preparation. A three‐constant equation of the following form applies: σ(T) = σ0′ exp(E / 2kT0) exp(−E / 2kT) where T0 is a new constant, the “characteristic temperature” of the substance. A method of evaluating σ0′ and T0 is to vary the activation energy for semiconduction by any of at least three processes: (1) hydration of the crystals; (2) formation of weak donor–acceptor complexes; (3) using different cis–trans isomers of the substance when possible. One method of evaluating the constants is to plot logσ0vs E. The slope of this line yields (2kT0)−1, and the intercept yields σ0′. Other methods are possible and yield consistent results. These methods are demonstrated for the substances oxidized cholesterol, retinal, and...

Summary The photoconductive and photovoltaic behaviour of a s-carotene glass cell is analyzed with regard to the effects of electric field strengths, polarity, and wave length dependence of the photoliberated electronic charge. These results have lead to a primitive theory of the electroretinogram. The four postulates of the theory are: 1. The generator potentials of the retina arise from a current source in the rod and cone outer segments. These currents are electronic charge transport processes created by the absorption of light by the visual pigments. 2. The component P II of the electroretinogram arises as a photocurrent in the retina due to the presence in the dark of an electric field in the receptor organ. 3. The component P III of the electroretinogram arises as a photovoltaic current in the receptor organ. 4. The electric field in the receptor organ arises from a potential gradient between the synaptic and the free end of the receptor. The polarity of the field being the base of the receptor negative with respect to the free end. These postulates of the theory, taken in conjunction with the experimentally determined characteristics of the photoconduction and photovoltaic effects are capable of commenting on or explaining the signs and shapes of the diphasic and monophasic electroretinograms; the localization measurements on generator potentials; the effects of depolarizing agents on the electroretinograms; the ontogenetic order of development of P III and P II; the similarity of sign of P III in vertebrate and invertebrate eyes; the presence of two components in the monophasic curves of invertebrate eyes; the signs, shapes, time constants, and wave length dependence of the graded photopic response; and lastly the characteristics of on/off receptors. Some difficulties and limitations of the theory are discussed.

A discussion is given of some theoretical and experimental aspects of photoconductivity in β‐carotene. It is shown that re‐solidification of crystalline β‐carotene results in the formation of a glass state which is photoconductive. The original all trans form is converted into a mixture of stereoisomers in the glass, and the appearance of the ``cis peak'' at 3500 A in the optical absorption spectrum is noted.The photoconductive action spectrum of a sandwich‐type cell of the β‐carotene glass has a maximum in this cis peak region when the electrodes are biased in the forward rectifying direction. The interpretation given to this in terms of the triplet state theory of photoconduction is that intersystem crossing is more probable from the cis peak than from the first excited state. Some evidence exists from semiconduction and phosphorescence measurements that the active triplet state lies 3.0 ev above the ground state and thus falls in the region between the two singlet excited states. Thus, the temperature dependent Boltzmann factor may be largely responsible for the increase in intersystem crossing from the cis peak state.The photocurrent in the back rectification direction is shown to be due to the light which is mostly transmitted through the glass and absorbed at the positive rear electrode. For strongly absorbed wavelengths the rectification ratio is 1.6×105.The voltage dependence is described by the sum of a linear term and a three halves power term, the former of which dominates at low field strengths and low absorption of the exciting light. There is a linear dependence of the photocurrent upon intensity.The similarity of the effects of cis‐trans isomerization in phosphorescence and photoconductive studies strongly suggests that the intersystem crossing to the triplet state is the dominant element in common and is considered as strong corroborating evidence for the triplet state theory of photoconduction in organic materials.

A variety of electrochemical events occurring on a bimolecular membrane of oxidized cholesterol have been detected. With solutions of I2 in NaI on one side and safranine on the other side of the membrane, an electric field in one direction causes a stable precipitate of high electrical resistance to form on the membrane. This can be erased by the reverse field direction. This precipitate can be visually observed, and decreases the electrical conductivity of the membrane. With solutions of I2 in NaI on one side and Hg(NO3)2 on the other, the application of 50 mv. across the membrane creates a specularly reflecting metallic film on the membrane surface. We suggest that this is strong evidence of coupled oxidation-reduction reactions occurring across the membrane and mediated by electron transport through the membrane. Application of higher voltages (≥ 100 millivolts) changes the dominant charge carrier to an ionic form (J3−—?) which forms visible precipitates of mercuric iodide. With a solution of NaI on one side and safranine on the other, an electric field in one direction causes a stable increase of conductance of the membrane.

The 1:1 electron donor-acceptor complexes of 2,4-dinitrophenol with lipids such as egg lecithin, synthetic lecithin and oxidized cholesterol have been studied spectrophoto-metrically in carbon tetrachloride solution. The charge-transfer absorption band has been found in the near ultraviolet for each complex. The equilibrium constants of these complexes have been estimated from their charge transfer bands and are in the order egg lecithin > synthetic lecithin > oxidized cholesterol. The electrical conductivity of bimolecular lipid membranes increases in the presence of iodine, picric acid, 2,4-dinitrophenol and trinitrobenzene. With increasing temperature, the electrical conductivity of bimolecular lipid membranes of oxidized cholesterol has been found to increase exponentially and the activation energies have been measured for membranes in bathing solutions of iodine, picric acid, 2,4-dinitrophenol, trinitrobenzene and water. The increase of electrical conductivity with decreasing activation energy of oxidized cholesterol bimolecular lipid membranes in the presence of different acceptors supports the suggestion of donor-acceptor complex formation. The strength of the acceptors are in the order iodine > picric acid > 2,4-dinitrophenol > trinitrobenzene. In the solid state, the activation energies of fully hydrated oxidized cholesterol crystals and also in the presence of iodine and 2,4-dinitrophenol have been measured. The values are in good agreement with those obtained for the bimolecular lipid membranes and suggest that the same mechanism of semiconduction appears in both cases.

— A new membrane photoeffect of high quantum efficiency is reported. The presence of a number of inorganic ions in the bathing solution of a bimolecular lipid film of oxidized cholesterol causes a change in the measured e.m.f. from -100 to -40 mV (photo e.m.f. effect) and increase in the conductivity by a factor of 100–200 (photoconductive effect) when the ions are excited by light. A model system, based upon the classical Becquerel Effect phenomenon of electronic charge injection into the membrane from electronically excited ions, is suggested and experiments verifying this model are reported. An extension of this model is used to suggest a new mechanism of the visual receptor process in biological photoreceptor structures.

The de semiconductive behavior of lipid films (cholesterol palmitate, egg lecithin and synthetic lecithin) has been studied. Although these lipids are insulators in the dry state, they exhibit conductivities greater than 108 times larger in the fully hydrated condition. The semiconduction activation energies for the “dry” and fully hydrated states of these films have been measured: for synthetic lecithin, the “dry” activation energy has values of 4.8 to 6.3 eV depending upon the sample, while for cholesterol palmitate the values range from 2.9 to 3.5 eV. The fully hydrated values for the lecithins range from 1.7 to 2.8 eV, whereas those for the cholesterol palmitate are 1.2 to 1.9 eV. For egg lecithin, an effect paralleling that for hydration is found upon exposure of the film to iodine vapor. Lipid bilayers, formed from egg lecithin, exhibit resistance values of 108Ω·cm2 when formed in distilled water. Addition of iodine to the water drops the resistance to less than 104Ω·cm2. Spectroscopic evidence indicates that iodine forms a donor-acceptor complex both with egg lecithin films and egg lecithin bilayers. The increase in electrical conductivity in both the lipid films and lipid bilayers is taken to be due to the formation of this donor—acceptor complex. Since all presently known donor—acceptor complexes are electronic conductors this is taken as suggestive of an electronic conduction mechanism in the bilayer.

Solid state electrolysis experiments were performed on the biomolecules, hemoglobin, cytochromec, collagen, lecithin and melanin at various hydration states; and for hemoglobin at various solvation states with methanol adsorbate. The evolved hydrogen was measured and compared with theoretical (Faraday's Law) expectations for the known amount of charge passed through the adsorbents. The difference between the theoretical and actual is a measure of the contributions of electronic charge carriers to the total current. Thus the protonic/electronic conduction ratios are determined.

Certain group VIIIB transition metal compounds were found to inhibit cell division in Escherichia coli , causing marked filamentous growth. Gram-negative bacilli were the most sensitive to this effect, whereas gram-positive bacilli responded only at near-toxic levels of the metal. None of the cocci tested showed any apparent effect. Cytokinesis (cross-septation) can be initiated by removal or decrease of platinum, but not by treatment with pantoyl lactone, divalent cations, or a temperature of 42 C.

Evidence has been presented to show that crystalline bovine hemoglobin is a semiconductor in the dry state. The semiconduction activation energy is 2.3 ev. This is similar to the values obtained for a number of other proteins, chromoproteins, and biological structures which have proteins as the main constituent. The effect of adsorbed water is to increase the conductivity enormously. The dependence on the amount of adsorbed water is exponential, in agreement with the results of Baxter and Spivey. In the ``wet'' state, the protein is still a semiconductor, but the semiconduction activation energy is lower. The dependence of the activation energy on the amount of adsorbed water is given by EW=ED−δm.I t has been proved that this is the only effect of water in causing the increase in conductivity. The value of σ0 in the semiconduction formula is 7×103[Ω—cm]—1 and is independent of the adsorbed water content. The effect of water adsorption on the conductivity is reversible when the water is desorbed. Experimen...

— The radiative fluorescence lifetimes of the all-trans, 9 cis and 13 cis retinol, have been measured at various temperatures, and in various solvents. The comparison of these results and of the data calculated from the absorption spectra using the Strickler and Berg equation shows that the transition probabilities are at least one hundred times lower for the radiative emission than for the absorption. Such a discrepancy, which is a general property of the polyenic structure, is closely related to the magnitude of the shift between absorption and fluorescence spectra. We interpret the observed elongation of the radiative fluorescence lifetimes and the temperature dependence of the radiative transitions in the case of all trans retinol as being due to the fact that only the lowest vibrorotational sublevels of 1S1, have a reasonable radiative transition probability: the temperature dependence of the radiationless transitions is considered to be due to the existence of a non radiative decay pathway at 550cal/mole above the ‘0’ level.

The presence of adsorbed oxygen gas increases the magnitude of the surface semiconduction currents in crystalline powder β‐carotene by a factor of about 103. The activation energy for the surface semiconduction process is 1.52 ev in argon gas and is decreased to 1.29 ev in oxygen. The room temperature photo‐current is increased by a factor of about 25 in oxygen over the value in argon. The activation energy of the photoconduction process is not affected by oxygen. The increase in dark current in an oxygen ambient requires a time of about 2 hr to come to the equilibrium value at room temperature. Radiation is not required to cause the increase. The effect of the oxygen can be reversed completely by heating the β‐carotene to 120°C in an inert atmosphere (dry nitrogen or argon). The increase in dark current is linearly proportional to the partial pressure of oxygen in the chamber. The rate of desorption of the oxygen increases with the temperature. The resulting data yield an activation energy of desorption ...

The activation energies for photoconduction have been measured in all trans and 15–15′ cis β‐carotene powders and in β‐carotene glass consisting of a mixture of isomers. The average values of a number of measurements of each are all trans, 0.37 ev; 15–15′ cis, 0.20 ev; isomerized glass, 0.19 ev. The values predicted by the triplet state theory of photoconduction are 0.35 (or 0.53), 0.18, and 0.18 ev, respectively. The larger activation energy (two or three vibrational quanta) of the all trans is attributed to the thermal energy necessary to allow an intersystem crossing from the first singlet excited state (about 2.6 ev) to the triplet state (about 3.0 ev). The activation energy of the cis‐trans forms of the molecule (1 vibrational quanta) correspond to intersystem crossing from the ``cis peak'' state (about 3.5 ev) to the triplet state. The excitation spectrum of photoconduction in 15–15′ cis β‐carotene and isomerized glass, peaks in the ``cis peak'' region, in agreement with this assignment. These results, that intersystem crossing occurs more readily from the cis peak state than the first singlet excited state, provide an explanation for the shape of the photocurrent excitation spectra in β‐carotene and for the lack of phosphorescence in all trans lycopene as reported by Lewis and Kasha.

Studies are reported on persistent internal polarization effects. This polarization can be produced, particularly in photoconductive, fluorescent substances of high dark resistance, by the action of various kinds of radiation in the presence of a dc electric field. It has been found that such polarizations, of more than 10 000 volts/cm, will persist for many days if kept in the dark after field removal. A material so polarized is in many ways a photosensitive electret. Among the substances tested, a [Zn: Cd]S phosphor and anthracene were used most extensively. Measurements are reported on the effect of ultraviolet, visible, and infrared light, gamma and beta rays on the production and removal of polarization. The increase of polarization with time is initially rapid and then shows saturation. It is almost a logarithmic function of the exciting radiation intensity, and a linear function of the polarizing voltage over a wide range. It is found that the equilibrium values of polarization are essentially determined by the applied voltage, and one parameter specific to the substance. Data are given on the long-time storage of polarization. It is shown that this polarization is due to a partial separation by the applied field of free mobile charges produced by the radiation inside the material and their localization in traps. It is not a charge injection-ejection phenomenon at the electrodes since it occurs just as well in samples insulated from the electrodes. In powders at least, the polarization is distributed throughout the entire sample and is not a charge accumulation near the surfaces. A correlation is established between these phenomena and the mechanism assumed for these substances to explain photoconductivity and fluorescence. A phenomenological model is presented which quantitatively describes many of the results of these experiments. This polarization effect provides a new method to detect and study energy storage in crystals.

The survivorship curves for Drosophila melanogaster, determined from experiments in which the flies are individually housed, are better fitted by a two-constant power law of the form, −1/N(dN/dt) = Atn, than by the Gompertz function: −1/N(dN/dt) = R0eαt. Such curves, taken for different ambient temperatures, show that A is a strong function of temperature, while n is not. Over the limited temperature range of the experiments (25–33°C), and Arrhenius plot is obtained for A, yielding an activation enthalpy for death ( ΔH † ) of 190 kcal/mole. This value is much higher than that reported by Strehler of 18.4 kcal/mole, but is consistent with the high activation enthalpies reported for unicellular organisms and mammalian cells in tissue culture. The power law plots, in either differential or integral form, appear to be generally applicable to mammalian age-related death statistics as shown by data on mice, rats and humans. The values of n are approximately 4–5 for all species tested. For human mortality rates, the three major individual causes of death are also well represented by power law plots. The ordinary distribution laws of the theory of probability do not give the correct forms for the mortality rates. However, the asymptotic distribution of extremes in order statistics do yield both the power law and the Gompertz function distributions. We speculate that the existence of high values of activation enthalpies for death predict that small decreases in core body temperatures of homeothermic mammals should produce marked increases in life expectancy.

The presence of various adsrobed gases increases the semiconduction currents in crystalline powder of β‐carotene by several orders of magnitude and decreases the activation energy for semiconduction. The current increase depends on the amount and nature of the adsorbed gas. The process is reversible simply by desorbing the gases. The kinetics of the conductivity rise follow the Roginsky‐Zeldovich equation for the adsorption‐time correlation. It has been noted that the adsorbed gases have no effect on the σ0 term, i.e., the mobilities of the charge carriers and the number of conducting states do not change. A value of σ0 ≈ 1.0 × 10−3(Ω·cm)−1 has been measured. Assuming a value for the radius of polarization field, R = 5.3 A and using the measured values of the dielectric constant, values for the activation energies of β‐carotene with adsorbed O2 and methanol, and also the increment in current expected, have been predicted. The measured values are in good agreement with these. We conclude that the changes i...