Scaling theory of transport in complex networks

Transport is an important function in many network systems and understanding its behavior on biological, social, and technological networks is crucial for a wide range of applications. However, it is a property that is not well-understood in these systems and this is probably due to the lack of a general theoretical framework. Here, based on the finding that renormalization can be applied to bio-networks, we develop a scaling theory of transport in self-similar networks. We demonstrate the networks invariance under length scale renormalization and we show that the problem of transport can be characterized in terms of a set of critical exponents. The scaling theory allows us to determine the influence of the modular structure on transport. We also generalize our theory by presenting and verifying scaling arguments for the dependence of transport on microscopic features, such as the degree of the nodes and the distance between them. Using transport concepts such as diffusion and resistance we exploit this invariance and we are able to explain, based on the topology of the network, recent experimental results on the broad flow distribution in metabolic networks.Comment: 8 pages, 6 figure

Global Gene Expression Characterization of Circulating Tumor Cells in Metastasic Castration-Resistant Prostate Cancer Patients

BACKGROUND: Current therapeutic options in the course of metastatic castration-resistant prostate cancers (mCRPC) reinforce the need for reliable tools to characterize the tumor in a dynamic way. Circulating tumor cells (CTCs) have emerged as a viable solution to the problem, whereby patients with a variety of solid tumors, including PC, often do not have recent tumor tissue available for analysis. The biomarker characterization in CTCs could provide insights into the current state of the disease and an overall picture of the intra-tumor heterogeneity. METHODS: in the present study, we applied a global gene expression characterization of the CTC population from mCRPC (n = 9), with the goal to better understand the biology of these cells and identify the relevant molecules favoring this tumor progression. RESULTS: This analysis allowed the identification of 50 genes specifically expressed in CTCs from patients. Six of these markers (HOXB13, QKI, MAOA, MOSPD1, SDK1, and FGD4), were validated in a cohort of 28 mCRPC, showing clinical interest for the management of these patients. Of note, the activity of this CTC signature was related to the regulation of MYC, a gene strongly implicated in the biology of mCRPC. CONCLUSIONS: Overall, our results represent new evidence on the great value of CTCs as a non-invasive biopsy to characterize PC

Phenomenological Determination of the Beauty Meson Decay Parameter fBf_B and the CP-Violating Angle δ\delta

We fit the ${\cal CKM}$-matrix to all recent data with the following free parameters: three mixing angles, the CP-violating angle $\delta$ in the Maiani parametrisation, the top quark mass $m_t$, and the product f_B{\cal B}_{\B}^{1/2}, where $f_B$ is the $B$-meson decay parameter and {\cal B}_{\B} is the bag parameter. Our fits span a contiguous region in the (f_B{\cal B}_{\B}^{1/2},\ \cos\delta)--plane, limited by 0.117\lsim f_B{\cal B}_{\B}^{1/2}/{\rm GeV}\lsim 0.231 and --0.95 \lsim $\cos\delta$ \lsim 0.70. The parameters f_B{\cal B}_{\B}^{1/2} and $\cos\delta$ are strongly positively correlated.Comment: 9 pages + 1 figure available upon request, HU-TFT-94-3

Pass a Law, Any Law, Fast! State Legislative Responses to the Kelo Backlash

The Supreme Court in Kelo v. City of New London left protection of property against takings for economic development to the states. Since Kelo, thirty-seven states have enacted legislation to update their eminent domain laws. This paper is the first to theoretically and empirically analyze the factors that influence whether, in what manner, and how quickly states change their laws through new legislation. Fourteen of the thirty-seven new laws offer only weak protections against development takings. The legislative response to Kelo was responsive to measures of the backlash but only in the binary decision whether to pass any new law. The decision to enact a meaningful restriction was more a function of relevant political economy measures. States with more economic freedom, greater value of new housing construction, and less racial and income inequality are more likely to have enacted stronger restrictions, and sooner. Of the thirteen states that have not updated, Arkansas, Oklahoma and Mississippi are highly likely to do so in the future. Hawaii, Massachusetts and New York are unlikely to update ever if at all

Patient-Reported Outcomes in ATLAS and FLAIR Participants on Long-Acting Regimens of Cabotegravir and Rilpivirine Over 48 Weeks

The phase 3 ATLAS and FLAIR studies demonstrated that maintenance with Long-Acting (LA) intramuscular cabotegravir and rilpivirine is non-inferior in efficacy to current antiretroviral (CAR) oral therapy. Both studies utilized Patient-Reported Outcome instruments to measure treatment satisfaction (HIVTSQ) and acceptance (ACCEPT general domain), health status (SF-12), injection tolerability/acceptance (PIN), and treatment preference. In pooled analyses, LA-treated patients (n = 591) demonstrated greater mean improvements from baseline than the CAR group (n = 591) in treatment satisfaction (Week 44, + 3.9 vs. +0.5 HIVTSQs-points; p /= 97% of LA group participants with recorded data preferred LA treatment compared with prior oral therapy. These results further support the potential of a monthly injectable option for people living with HIV seeking an alternative to daily oral treatment

FKF1 conveys timing information for CONSTANS stabilization in photoperiodic flowering

Plants use day-length information to coordinate flowering time with the appropriate season to maximize reproduction. In Arabidopsis, the long-day specific expression of CONSTANS (CO) protein is crucial for flowering induction. Although light signaling regulates CO protein stability, the mechanism by which CO is stabilized in the long-day afternoon has remained elusive. Here we demonstrate that FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) protein stabilizes CO protein in the afternoon in long days. FKF1 interacts with CO through its LOV domain, and blue light enhances this interaction. In addition, FKF1 simultaneously removes CYCLING DOF FACTOR 1 (CDF1) that represses CO and FLOWERING LOCUS T (FT) transcription. Together with CO transcriptional regulation, FKF1 protein controls robust FT mRNA induction through multiple feedforward mechanisms that accurately control flowering timing

Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study

Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic "risk" and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke's R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome

Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years