Power laws of complex systems from Extreme physical information

Many complex systems obey allometric, or power, laws y=Yx^{a}. Here y is the measured value of some system attribute a, Y is a constant, and x is a stochastic variable. Remarkably, for many living systems the exponent a is limited to values +or- n/4, n=0,1,2... Here x is the mass of a randomly selected creature in the population. These quarter-power laws hold for many attributes, such as pulse rate (n=-1). Allometry has, in the past, been theoretically justified on a case-by-case basis. An ultimate goal is to find a common cause for allometry of all types and for both living and nonliving systems. The principle I - J = extrem. of Extreme physical information (EPI) is found to provide such a cause. It describes the flow of Fisher information J => I from an attribute value a on the cell level to its exterior observation y. Data y are formed via a system channel function y = f(x,a), with f(x,a) to be found. Extremizing the difference I - J through variation of f(x,a) results in a general allometric law f(x,a)= y = Yx^{a}. Darwinian evolution is presumed to cause a second extremization of I - J, now with respect to the choice of a. The solution is a=+or-n/4, n=0,1,2..., defining the particular powers of biological allometry. Under special circumstances, the model predicts that such biological systems are controlled by but two distinct intracellular information sources. These sources are conjectured to be cellular DNA and cellular transmembrane ion gradient

Search for the electric dipole excitations to the 3s1/2⊗[21+⊗31−]3s_{1/2} \otimes [2^{+}_{1} \otimes 3^{-}_{1}] multiplet in 117^{117}Sn

The odd-mass $^{117}$Sn nucleus was investigated in nuclear resonance fluorescence experiments up to an endpoint energy of the incident photon spectrum of 4.1 MeV at the bremsstrahlung facility of the Stuttgart University. More than 50 mainly hitherto unknown levels were found. From the measurement of the scattering cross sections model independent absolute electric dipole excitation strengths were extracted. The measured angular distributions suggested the spins of 11 excited levels. Quasi-particle phonon model calculations including a complete configuration space were performed for the first time for a heavy odd-mass spherical nucleus. These calculations give a clear insight in the fragmentation and distribution of the $E1$, $M1$, and $E2$ excitation strength in the low energy region. It is proven that the $1^{-}$ component of the two-phonon $[2^{+}_{1} \otimes 3^{-}_{1}]$ quintuplet built on top of the $1/2^{+}$ ground state is strongly fragmented. The theoretical calculations are consistent with the experimental data.Comment: 10 pages, 5 figure

Novel Role of the IGF-1 Receptor in Endothelial Function and Repair: Studies in Endothelium-Targeted IGF-1 Receptor Transgenic Mice

We recently demonstrated that reducing IGF-1 receptor (IGF-1R) numbers in the endothelium enhances nitric oxide (NO) bioavailability and endothelial cell insulin sensitivity. In the present report, we aimed to examine the effect of increasing IGF-1R on endothelial cell function and repair. To examine the effect of increasing IGF-1R in the endothelium, we generated mice overexpressing human IGF-1R in the endothelium (human IGF-1R endothelium-overexpressing mice [hIGFREO]) under direction of the Tie2 promoter enhancer. hIGFREO aorta had reduced basal NO bioavailability (percent constriction to NG-monomethyl-l-arginine [mean (SEM) wild type 106% (30%); hIGFREO 48% (10%)]; P < 0.05). Endothelial cells from hIGFREO had reduced insulin-stimulated endothelial NO synthase activation (mean [SEM] wild type 170% [25%], hIGFREO 58% [3%]; P = 0.04) and insulin-stimulated NO release (mean [SEM] wild type 4,500 AU [1,000], hIGFREO 1,500 AU [700]; P < 0.05). hIGFREO mice had enhanced endothelium regeneration after denuding arterial injury (mean [SEM] percent recovered area, wild type 57% [2%], hIGFREO 47% [5%]; P < 0.05) and enhanced endothelial cell migration in vitro. The IGF-1R, although reducing NO bioavailability, enhances in situ endothelium regeneration. Manipulating IGF-1R in the endothelium may be a useful strategy to treat disorders of vascular growth and repair. Insulin-resistant type 2 diabetes characterized by perturbation of the insulin/IGF-1 system is a multisystem disorder of nutrient homeostasis, cell growth, and tissue repair (1). As a result, type 2 diabetes is a major risk factor for the development of a range of disorders of human health, including occlusive coronary artery disease (2), peripheral vascular disease (3), stroke (4), chronic vascular ulcers (5), proliferative retinopathy (6), and nephropathy (7). A key hallmark of these pathologies is endothelial cell dysfunction characterized by a reduction in bioavailability of the signaling radical nitric oxide (NO). In the endothelium, insulin binding to its tyrosine kinase receptor stimulates release of NO (8). Insulin resistance at a whole-body level (9,10) and specific to the endothelium (11) leads to reduced bioavailability of NO, indicative of a critical role for insulin in regulating NO bioavailability. The insulin receptor (IR) and IGF-1 receptor (IGF-1R) are structurally similar—both composed of two extracellular α and two transmembrane β subunits linked by disulfide bonds (12). As a result, IGF-1R and IR can heterodimerize to form insulin-resistant hybrid receptors composed of one IGF-1R-αβ complex and one IR-αβ subunit complex (13,14). We recently demonstrated that reducing IGF-1R (by reducing the number of hybrid receptors) enhances insulin sensitivity and NO bioavailability in the endothelium (15). To examine the effect of increasing IGF-1R specifically in the endothelium on NO bioavailability, endothelial repair, and metabolic homeostasis, we generated a transgenic mouse with targeted overexpression of the human IGF-1R in the endothelium (hIGFREO)

Coupled-channels analysis of the 16^{{\bf 16}}O+208^{{\bf 208}}Pb fusion barrier distribution

Analyses using simplified coupled-channels models have been unable to describe the shape of the previously measured fusion barrier distribution for the doubly magic $^{16}$O+$^{208}$Pb system. This problem was investigated by re-measuring the fission excitation function for $^{16}$O+$^{208}$Pb with improved accuracy and performing more exact coupled-channels calculations, avoiding the constant-coupling and first-order coupling approximations often used in simplified analyses. Couplings to the single- and 2-phonon states of $^{208}$Pb, correctly taking into account the excitation energy and the phonon character of these states, particle transfers, and the effects of varying the diffuseness of the nuclear potential, were all explored. However, in contrast to other recent analyses of precise fusion data, no satisfactory simultaneous description of the shape of the experimental barrier distribution and the fusion cross-sections for $^{16}$O+$^{208}$Pb was obtained.Comment: RevTex, 29 pages, 7 postscript figures, to appear in PR

Prisoner's Dilemma in Cancer Metabolism

As tumors outgrow their blood supply and become oxygen deprived, they switch to less energetically efficient but oxygen-independent anaerobic glucose metabolism. However, cancer cells maintain glycolytic phenotype even in the areas of ample oxygen supply (Warburg effect). It has been hypothesized that the competitive advantage that glycolytic cells get over aerobic cells is achieved through secretion of lactic acid, which is a by-product of glycolysis. It creates acidic microenvironment around the tumor that can be toxic to normal somatic cells. This interaction can be seen as a prisoner's dilemma: from the point of view of metabolic payoffs, it is better for cells to cooperate and become better competitors but neither cell has an incentive to unilaterally change its metabolic strategy. In this paper a novel mathematical technique, which allows reducing an otherwise infinitely dimensional system to low dimensionality, is used to demonstrate that changing the environment can take the cells out of this equilibrium and that it is cooperation that can in fact lead to the cell population committing evolutionary suicide

The impact of cave lighting on the bioluminescent display of the Tasmanian glow-worm Arachnocampa tasmaniensis

Bioluminescent larvae of the dipteran genus Arachnocampa are charismatic microfauna that can reach high densities in caves, where they attract many visitors. These focal populations are the subjects of conservation management because of their high natural and commercial value. Despite their tourism importance, little is known about their susceptibility and resilience to natural or human impacts. At Marakoopa Cave in northern Tasmania, guided tours take visitors through different chambers and terminate at a viewing platform where the cave lighting is extinguished and a glowing colony of Arachnocampa tasmaniensis (Diptera: Keroplatidae) larvae on the chamber ceiling is revealed. Research has shown that exposure to artificial light can cause larvae to douse or dim their bioluminescence; hence, the cave lighting associated with visitor access could reduce the intensity of the natural display. We used time-lapse digital photography to record light output over 10 days to determine whether cave lighting affects the intensity or rhythmicity of bioluminescence. Simultaneously, another colony in a different section of the cave, away from tourist activity, was photographed over 3 days. Both colonies showed high-amplitude 24 h cycling of bioluminescence intensity, with the peak occurring at 11.50 h at the unvisited site and 12.50 h at the main chamber, so the time of peak display did not appear to be substantially affected by light exposure. Intermittent light exposure experienced by larvae in the main chamber caused detectable reductions in bioluminescence intensity; however, recovery was rapid and the overall shape of the daily bioluminescence curve closely matched that of the unvisited colony. In conclusion, the artificial light exposure regime used in Marakoopa Cave does not have a substantial effect on the timing or quality of the bioluminescence display. The time-lapse photographic monitoring method could be permanently implemented at focal tourism sites to provide information about daily, seasonal and annual fluctuations in the displays, the response to events such as drought and flood, and the population's ability to recover from adverse conditions

A Taxonomy of Causality-Based Biological Properties

We formally characterize a set of causality-based properties of metabolic networks. This set of properties aims at making precise several notions on the production of metabolites, which are familiar in the biologists' terminology. From a theoretical point of view, biochemical reactions are abstractly represented as causal implications and the produced metabolites as causal consequences of the implication representing the corresponding reaction. The fact that a reactant is produced is represented by means of the chain of reactions that have made it exist. Such representation abstracts away from quantities, stoichiometric and thermodynamic parameters and constitutes the basis for the characterization of our properties. Moreover, we propose an effective method for verifying our properties based on an abstract model of system dynamics. This consists of a new abstract semantics for the system seen as a concurrent network and expressed using the Chemical Ground Form calculus. We illustrate an application of this framework to a portion of a real metabolic pathway

Transketolase-Like 1 Expression Is Modulated during Colorectal Cancer Progression and Metastasis Formation

Background Transketolase-like 1 (TKTL1) induces glucose degradation through anaerobic pathways, even in presence of oxygen, favoring the malignant aerobic glycolytic phenotype characteristic of tumor cells. As TKTL1 appears to be a valid biomarker for cancer prognosis, the aim of the current study was to correlate its expression with tumor stage, probability of tumor recurrence and survival, in a series of colorectal cancer patients. Methodolody/Principal Findings Tumor tissues from 63 patients diagnosed with colorectal cancer at different stages of progression were analyzed for TKTL1 by immunohistochemistry. Staining was quantified by computational image analysis, and correlations between enzyme expression, local growth, lymph-node involvement and metastasis were assessed. The highest values for TKTL1 expression were detected in the group of stage III tumors, which showed significant differences from the other groups (Kruskal-Wallis test, P = 0.000008). Deeper analyses of T, N and M classifications revealed a weak correlation between local tumor growth and enzyme expression (Mann-Whitney test, P = 0.029), a significant association of the enzyme expression with lymph-node involvement (Mann-Whitney test, P = 0.0014) and a significant decrease in TKTL1 expression associated with metastasis (Mann-Whitney test, P = 0.0004). Conclusions/Significance To our knowledge, few studies have explored the association between variations in TKTL1 expression in the primary tumor and metastasis formation. Here we report downregulation of enzyme expression when metastasis appears, and a correlation between enzyme expression and regional lymph-node involvement in colon cancer. This finding may improve our understanding of metastasis and lead to new and more efficient therapies against cancer

Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP® Peptides) Conjugated with Different Fluorescent Dyes

Purpose Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP® peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors. Procedures Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP® variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP® variants in multidimensional space of spectral parameters. Results The fluorescently labeled pHLIP® variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP® peptide. Conclusions Different cargo molecules conjugated with pHLIP® peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP®-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions

Captive breeding of Margaritifera auricularia (Spengler, 1793) and its conservation importance

Margaritifera auricularia is one of the most endangered freshwater mussels (Bivalvia, Unionida) in the world. Since 2013, the abundance of this species in the Ebro River basin (Spain) has sharply declined, driving the species to the verge of regional extinction. Therefore, any management measures that might facilitate the recovery of this species would be essential for its conservation. During 2014–2016, captive breeding of M. auricularia allowed the production of >106 juveniles, out of which 95% were released into the natural environment, and 5% were grown in the laboratory under controlled conditions. The aim of this experimental work was to establish the best culture conditions for the survival and growth of M. auricularia juveniles in the laboratory. The experiment was divided into two phases: phase I, in which juveniles recently detached from fish gills were cultured in detritus boxes until they reached a shell length of 1 mm; and phase II, in which these specimens were transferred to larger aquaria to grow up to 3–4 mm. The best experimental conditions for juvenile survival and growth corresponded to treatments in glass containers at a density of 0.2 ind. L−1, using river water, with added substrate and detritus, enriched with phytoplankton, and avoiding extra aeration. The highest survival and growth rates attained, respectively, values of c. 60% at 100 days and 2.56 mm in shell length at 30–32 weeks. This is the first study to report on the long‐term survival and growth of juvenile M. auricularia in the laboratory, providing essential information in order to implement future conservation measures addressed at reinforcing the natural populations of this highly threatened species in European water bodies.This project was funded by the Government of Aragón, Department of Rural Development and Sustainability and carried out by the Environmental Service Department of SARGA. Special thanks go to Manuel Alcántara, Miguel Ángel Muñoz, Ester Ginés, Carlos Catalá, and Juan Pablo de la Roche, who were involved in the project. The authors appreciate the work of the reviewer and editor who improved the quality of the manuscript. The Aragón's forest rangers are thanked for their assistance during fieldwork