Fluctuation scaling in complex systems: Taylor's law and beyond

Complex systems consist of many interacting elements which participate in some dynamical process. The activity of various elements is often different and the fluctuation in the activity of an element grows monotonically with the average activity. This relationship is often of the form "$fluctuations \approx const.\times average^\alpha$", where the exponent $\alpha$ is predominantly in the range $[1/2, 1]$. This power law has been observed in a very wide range of disciplines, ranging from population dynamics through the Internet to the stock market and it is often treated under the names \emph{Taylor's law} or \emph{fluctuation scaling}. This review attempts to show how general the above scaling relationship is by surveying the literature, as well as by reporting some new empirical data and model calculations. We also show some basic principles that can underlie the generality of the phenomenon. This is followed by a mean-field framework based on sums of random variables. In this context the emergence of fluctuation scaling is equivalent to some corresponding limit theorems. In certain physical systems fluctuation scaling can be related to finite size scaling.Comment: 33 pages, 20 figures, 2 tables, submitted to Advances in Physic

Effects of buprenorphine on acute pain and inflammation in the adjuvant-induced monoarthritis rat model

Background and aim: Animal modelling of arthritis is often associated with pain and suffering. Severity may be reduced with the use of analgesia which is, however, often withheld due to concerns of introducing a confounding variable. It is therefore important to design and validate pain relief protocols that reduce pain without compromising the scientific objectives. The present study evaluated the effect of buprenorphine analgesia in the immediate post-induction period of an adjuvant-induced monoarthritic rat model. The aim of this study was to extend previous work on refinement of the model by alleviating unnecessary pain. Methods: Male and female Sprague Dawley rats were injected with 20 μl of complete Freund's adjuvant (CFA) into the left ankle. Rats were treated with buprenorphine, either injected subcutaneously or ingested voluntarily, and were compared to rats given subcutaneous injections with vehicle (saline or pure nut paste) or carprofen the first three days post CFA-injection. Measurements of welfare, clinical model-specific parameters and pain-related behaviour were assessed. Results: Buprenorphine, administered either subcutaneously (0.10 or 0.15 mg/kg, twice daily) or by voluntary ingestion in nut paste (1.0 or 3.0 mg/kg, twice daily), improved mobility, stance, rearing and lameness scores significantly 7 h post CFA-injection. Mechanical hyperalgesia peaked at 7 h and was significantly lower in buprenorphine-treated animals, compared to vehicle-treated animals. Joint circumference was highest 24–72 h after CFA injection. Animals treated with buprenorphine did not decrease in joint circumference, opposite carprofen treated animals. Conclusion: Buprenorphine, administered either subcutaneously or by voluntary ingestion, provides adequate analgesia for both sexes within the first 24 h post CFA-injection. Buprenorphine treatment improved clinical scores and appeared not to suppress the inflammatory response. The present study supports previous findings that voluntarily ingested buprenorphine is an effective alternative to repeated injections

Autocrine TNF-α production supports CML stem and progenitor cell survival and enhances their proliferation.

Chronic myeloid leukemia (CML) stem cells are not dependent on BCR-ABL kinase for their survival, suggesting that kinase-independent mechanisms must contribute to their persistence. We observed that CML stem/progenitor cells (SPCs) produce tumor necrosis factor-α (TNF-α) in a kinase-independent fashion and at higher levels relative to their normal counterparts. We therefore investigated the role of TNF-α and found that it supports survival of CML SPCs by promoting nuclear factor κB/p65 pathway activity and expression of the interleukin 3 and granulocyte/macrophage-colony stimulating factor common β-chain receptor. Furthermore, we demonstrate that in CML SPCs, inhibition of autocrine TNF-α signaling via a small-molecule TNF-α inhibitor induces apoptosis. Moreover TNF-α inhibition combined with nilotinib induces significantly more apoptosis relative to either treatment alone and a reduction in the absolute number of primitive quiescent CML stem cells. These results highlight a novel survival mechanism of CML SPCs and suggest a new putative therapeutic target for their eradication.This study was supported by the Glasgow Experimental Cancer Medicine Centre , which is funded by Cancer Research UK and by the Chief Scientist’s Office, Scotland. Cell sorting facilities were funded by the Kay Kendall Leukaemia Fund (KKL501) and the Howat Foundation. Funding was provided by Medical Research Council UK clinical research training fellowship grant G1000288 (P.G.), Cancer Research UK Programme grant C11074/A11008 and the Elimination of Leukaemia Fund (ELF/6/ 29/1) (F.P.), National Institutes of Health, National Cancer Institute research grant R01 CA095684 (R.B.), by the Friends of Paul O’Gorman Leukaemia Research Centre (H.G.J.), and Cancer Research UK Programme grant C11074/A11008 (T.L.H.)

Pressure-induced superconductivity in Eu0.5_{0.5}Ca0.5_{0.5}Fe2_2As2_2 : FeAs-based superconductivity hidden by antiferromagnetism of Eu sublattice

To clarify superconductivity in EuFe2As2 hidden by antiferromagnetism of Eu2+, we investigated a Ca-substituted sample, Eu0.5Ca0.5Fe2As2, under high pressure. For ambient pressure, the sample exhibits a spin-density-wave (SDW) transition at TSDW = 191 K and antiferromagnetic order at TN = 4 K, but no evidence of superconductivity down to 2 K. The Ca-substitution certainly weakens the antiferromagnetism. With increasing pressure, TSDW shifts to lower temperature and becomes more unclear. Above 1.27 GPa, pressure-induced superconductivity with zero resistivity is observed at around Tc = 20 K. At 2.14 GPa, Tc reaches a maximum value of 24 K and the superconducting transition becomes the sharpest. These features of emergence of the superconductivity are qualitatively similar to those observed in AFe2As2 (A = Ba, Ca).Comment: 4 pages, 4 figure

An update on semen quality among young Finnish men and comparison with Danish data

Finnish men used to have higher semen quality than Danish men. However, recent studies showed that semen quality in Finland has declined, but it has been relatively stable in Denmark.\nThis study aimed to compare new data on semen quality of the young Finnish men to that of Danish men.\nIn this cross-sectional study, 18- to 19-year-old men residing in Turku, Finland and Copenhagen, Denmark, were invited to participate in 2008-2011. Each man filled in a questionnaire, provided one semen sample and underwent andrological examination. Semen samples were analyzed according to WHO. Multiway ANOVA was used to adjust semen variables for duration of sexual abstinence and age (and time from ejaculation to the start of semen analysis for sperm motility).\nAltogether 287 Finnish men and 873 Danish men participated in the study. The adjusted median sperm concentrations were 49 and 47 million/mL for Finnish and Danish men, respectively (p = 0.48). The adjusted median total sperm counts were 148 million in Finland and 146 million in Denmark (p = 0.87). The adjusted median percentages of morphologically normal spermatozoa were 6.9% in Finland and 6.5% in Denmark, p = 0.27. Finnish men had higher adjusted median percentages of motile spermatozoa (A+B+C) than Danish men (80% vs. 69%, p < 0.001). The proportion of men who had low semen quality (sperm concentration, percentage of morphologically normal spermatozoa or percentage of progressively motile spermatozoa below WHO reference limits) was lower in Finland (25.4%) than in Denmark (34.6%), p = 0.004.\nConsiderable percentage of men in both countries had low semen quality. The deteriorating semen quality in Finland may result in decreasing fecundity, which is a cause of concern.\nThe formerly high semen quality in Finland has converged to the lower Danish levels. Our findings demonstrate the importance of continuing surveillance of semen quality.\nBACKGROUND\nOBJECTIVE\nMATERIALS AND METHODS\nRESULTS\nDISCUSSION\nCONCLUSIO

Active and diverse viruses persist in the deep sub-seafloor sediments over thousands of years

Viruses are ubiquitous and cause significant mortality in marine bacterial and archaeal communities. Little is known about the role of viruses in the sub-seafloor biosphere, which hosts a large fraction of all microbes on Earth. We quantified and characterized viruses in sediments from the Baltic Sea. The results show that the Baltic Sea sub-seafloor biosphere harbors highly abundant viruses with densities up to 1.8 × 1010 viruses cm−3. High potential viral production down to 37 meters below seafloor in ca. 6000-years-old sediments and infected prokaryotic cells visible by transmission electron microscopy demonstrate active viral infection. Morphological and molecular data indicate that the highly diverse community of viruses includes both allochthonous input from the overlying seawater and autochthonous production. The detection of cyanophage-like sequences showed that viruses of phototrophic hosts may persist in marine sediments for thousands of years. Our results imply that viruses influence sub-seafloor microbial community dynamics and thereby affect biogeochemical processes in the sub-seafloor biosphere

Differences in epitope-specific antibodies to pertussis toxin after infection and acellular vaccinations

Objectives: Pertussis toxin (PT) is a component of all acellular pertussis vaccines. PT must be detoxified to be included in acellular vaccines, which results in conformational changes in the functional epitopes of PTs. Therefore, induced epitope-specific antibodies to PT may vary after vaccinations or natural infections, and this information could reveal biomarkers implicated for protection and successful immunisation. Methods: Pertussis toxin epitope-specific antibodies in sera from 152 vaccinated children and 72 serologically confirmed patients were tested with a blocking ELISA, based on monoclonal antibodies that target protective PT epitopes. Results: All study groups induced considerable antibody titres to subunit 1 (S1). Of interest, S3 7E10-specific antibodies were present in patients, but not after vaccinations (P < 0.001). The impact of glutaraldehyde treatment of PT was visible on epitope 1D7 (S1), whereas epitopes 1B7 (S1) and 10D (S1) were more preserved. Antibodies to these epitopes were higher after three primary vaccine doses than after a single booster dose. Conclusion: The high amount of 7E10-specific antibodies in patients suggests this epitope might be functionally relevant in protection. The overall characteristics of epitope-specific antibodies are influenced by infection or vaccination background, by the used detoxification method of PT and by the amount of the toxin used in immunisation. </div

Machine learning can identify newly diagnosed patients with CLL at high risk of infection

Infections have become the major cause of morbidity and mortality among patients with chronic lymphocytic leukemia (CLL) due to immune dysfunction and cytotoxic CLL treatment. Yet, predictive models for infection are missing. In this work, we develop the CLL Treatment-Infection Model (CLL-TIM) that identifies patients at risk of infection or CLL treatment within 2 years of diagnosis as validated on both internal and external cohorts. CLL-TIM is an ensemble algorithm composed of 28 machine learning algorithms based on data from 4,149 patients with CLL. The model is capable of dealing with heterogeneous data, including the high rates of missing data to be expected in the real-world setting, with a precision of 72% and a recall of 75%. To address concerns regarding the use of complex machine learning algorithms in the clinic, for each patient with CLL, CLL-TIM provides explainable predictions through uncertainty estimates and personalized risk factors

Toward Improved Lifetimes of Organic Solar Cells under Thermal Stress: Substrate-Dependent Morphological Stability of PCDTBT:PCBM Films and Devices

Morphological stability is a key requirement for outdoor operation of organic solar cells. We demonstrate that morphological stability and lifetime of polymer/fullerene based solar cells under thermal stress depend strongly on the substrate interface on which the active layer is deposited. In particular, we find that the stability of benchmark PCDTBT/PCBM solar cells under modest thermal stress is substantially increased in inverted solar cells employing a ZnO substrate compared to conventional devices employing a PEDOT:PSS substrate. This improved stability is observed to correlate with PCBM nucleation at the 50 nm scale, which is shown to be strongly influenced by different substrate interfaces. Employing this approach, we demonstrate remarkable thermal stability for inverted PCDTBT:PC70BM devices on ZnO substrates, with negligible (<2%) loss of power conversion efficiency over 160 h under 85 °C thermal stress and minimal thermally induced “burn-in” effect. We thus conclude that inverted organic solar cells, in addition to showing improved environmental stability against ambient humidity exposure as widely reported previously, can also demonstrate enhanced morphological stability. As such we show that the choice of suitable substrate interfaces may be a key factor in achieving prolonged lifetimes for organic solar cells under thermal stress conditions