Random planar graphs and the London street network

In this paper we analyse the street network of London both in its primary and dual representation. To understand its properties, we consider three idealised models based on a grid, a static random planar graph and a growing random planar graph. Comparing the models and the street network, we find that the streets of London form a self-organising system whose growth is characterised by a strict interaction between the metrical and informational space. In particular, a principle of least effort appears to create a balance between the physical and the mental effort required to navigate the city

FETR-ALS Study Protocol: A Randomized Clinical Trial of Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis

Background and Rationale: Among the key players in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), microglia and T regulatory lymphocytes (Treg) are candidate cells for modifying the course of the disease. The gut microbiota (GM) acts by shaping immune tolerance and regulating the Treg number and suppressive function, besides circulating neuropeptides, and other immune cells that play in concert through the gut-brain axis. Previous mouse models have shown an altered enteric flora in early stage ALS, pointing to a possible GM role in ALS pathogenesis. Fecal Microbial Transplantation (FMT) is a well-known therapeutic intervention used to re-establish the proper microenvironment and to modulate enteric and systemic immunity. Methods: We are going to perform a multicenter randomized double-blind clinical trial employing FMT as a therapeutic intervention for ALS patients (NCT0376632). Forty-two ALS patients, at an early stage, will be enrolled with a 2:1 allocation ratio (28 FMT-treated patients vs. 14 controls). Study duration will be 12 months per patient. Three endoscopic procedures for intestinal biopsies in FMT and control groups are predicted at baseline, month 6 and month 12; at baseline and at month 6 fresh feces from healthy donors will be infused at patients in the intervention arm. The primary outcome is a significant change in Treg number between FMT-treated patients and control arm from baseline to month 6. Secondary outcomes include specific biological aims, involving in-depth analysis of immune cells and inflammatory status changes, central and peripheral biomarkers of ALS, besides comprehensive analysis of the gut, saliva and fecal microbiota. Other secondary aims include validated clinical outcomes of ALS (survival, forced vital capacity, and modifications in ALSFRS-R), besides safety and quality of life. Expected Results: We await FMT to increase Treg number and suppressive functionality, switching the immune system surrounding motorneurons to an anti-inflammatory, neuroprotective status. Extensive analysis on immune cell populations, cytokines levels, and microbiota (gut, fecal and saliva) will shed light on early processes possibly leading the degenerative ALS course. Conclusions: This is the first trial with FMT as a potential intervention to modify immunological response to ALS and disease progression at an early stage

Wikipedia Information Flow Analysis Reveals the Scale-Free Architecture of the Semantic Space

In this paper we extract the topology of the semantic space in its encyclopedic acception, measuring the semantic flow between the different entries of the largest modern encyclopedia, Wikipedia, and thus creating a directed complex network of semantic flows. Notably at the percolation threshold the semantic space is characterised by scale-free behaviour at different levels of complexity and this relates the semantic space to a wide range of biological, social and linguistics phenomena. In particular we find that the cluster size distribution, representing the size of different semantic areas, is scale-free. Moreover the topology of the resulting semantic space is scale-free in the connectivity distribution and displays small-world properties. However its statistical properties do not allow a classical interpretation via a generative model based on a simple multiplicative process. After giving a detailed description and interpretation of the topological properties of the semantic space, we introduce a stochastic model of content-based network, based on a copy and mutation algorithm and on the Heaps' law, that is able to capture the main statistical properties of the analysed semantic space, including the Zipf's law for the word frequency distribution

Limited Urban Growth: London's Street Network Dynamics since the 18th Century

We investigate the growth dynamics of Greater London defined by the administrative boundary of the Greater London Authority, based on the evolution of its street network during the last two centuries. This is done by employing a unique dataset, consisting of the planar graph representation of nine time slices of Greater London's road network spanning 224 years, from 1786 to 2010. Within this time-frame, we address the concept of the metropolitan area or city in physical terms, in that urban evolution reveals observable transitions in the distribution of relevant geometrical properties. Given that London has a hard boundary enforced by its long-standing green belt, we show that its street network dynamics can be described as a fractal space-filling phenomena up to a capacitated limit, whence its growth can be predicted with a striking level of accuracy. This observation is confirmed by the analytical calculation of key topological properties of the planar graph, such as the topological growth of the network and its average connectivity. This study thus represents an example of a strong violation of Gibrat's law. In particular, we are able to show analytically how London evolves from a more loop-like structure, typical of planned cities, toward a more tree-like structure, typical of self-organized cities. These observations are relevant to the discourse on sustainable urban planning with respect to the control of urban sprawl in many large cities, which have developed under the conditions of spatial constraints imposed by green belts and hard urban boundaries.Comment: PlosOne, in publicatio

Computational fact checking from knowledge networks

Traditional fact checking by expert journalists cannot keep up with the enormous volume of information that is now generated online. Computational fact checking may significantly enhance our ability to evaluate the veracity of dubious information. Here we show that the complexities of human fact checking can be approximated quite well by finding the shortest path between concept nodes under properly defined semantic proximity metrics on knowledge graphs. Framed as a network problem this approach is feasible with efficient computational techniques. We evaluate this approach by examining tens of thousands of claims related to history, entertainment, geography, and biographical information using a public knowledge graph extracted from Wikipedia. Statements independently known to be true consistently receive higher support via our method than do false ones. These findings represent a significant step toward scalable computational fact-checking methods that may one day mitigate the spread of harmful misinformation

A matter of life and death: the Middle Neolithic population from Bom Santo Cave (Lisbon, Portugal)

The study of the Bom Santo Cave (central Portugal), a Neolithic cemetery, indicated a complex social, palaeoeconomic and population scenario. With isotope, aDNA and provenience analyses of raw materials coupled with stylistic variability of material culture items and palaeogeographical data light is shed on the territory and social organization of a population dated to 3800–3400 cal BC, i.e. the middle phase of the period. Results indicate an itinerant farming, segmentary society, where exogamic practices were the norm and patrilocality probably predominated. Its lifeway may be that of the earliest megalithic builders of the region, but further research is needed to correctly evaluate the degree of participation in such phenomenon

Auxin transport through non-hair cells sustains root-hair development.

The plant hormone auxin controls root epidermal cell development in a concentration-dependent manner. Root hairs are produced on a subset of epidermal cells as they increase in distance from the root tip. Auxin is required for their initiation and continued growth, but little is known about its distribution in this region of the root. Contrary to the expectation that hair cells might require active auxin influx to ensure auxin supply, we did not detect the auxin-influx transporter AUX1 in root-hair cells. A high level of AUX1 expression was detected in adjacent non-hair cell files. Non-hair cells were necessary to achieve wild-type root-hair length, although an auxin response was not required in these cells. Three-dimensional modelling of auxin flow in the root tip suggests that AUX1-dependent transport through non-hair cells maintains an auxin supply to developing hair cells as they increase in distance from the root tip, and sustains root-hair outgrowth. Experimental data support the hypothesis that instead of moving uniformly though the epidermal cell layer, auxin is mainly transported through canals that extend longitudinally into the tissue

Recurrent Plasmodium falciparum Malaria Infections in Kenyan Children Diminish T-Cell Immunity to Epstein Barr Virus Lytic but Not Latent Antigens

Plasmodium falciparum malaria (Pf-malaria) and Epstein Barr Virus (EBV) infections coexist in children at risk for endemic Burkitt's lymphoma (eBL); yet studies have only glimpsed the cumulative effect of Pf-malaria on EBV-specific immunity. Using pooled EBV lytic and latent CD8+ T-cell epitope-peptides, IFN-γ ELISPOT responses were surveyed three times among children (10 months to 15 years) in Kenya from 2002–2004. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated in association with Pf-malaria exposure, defined at the district-level (Kisumu: holoendemic; Nandi: hypoendemic) and the individual-level. We observed a 46% decrease in positive EBV lytic antigen IFN-γ responses among 5–9 year olds residing in Kisumu compared to Nandi (PR: 0.54; 95% CI: 0.30–0.99). Individual-level analysis in Kisumu revealed further impairment of EBV lytic antigen responses among 5–9 year olds consistently infected with Pf-malaria compared to those never infected. There were no observed district- or individual-level differences between Pf-malaria exposure and EBV latent antigen IFN-γ response. The gradual decrease of EBV lytic antigen but not latent antigen IFN-γ responses after primary infection suggests a specific loss in immunological control over the lytic cycle in children residing in malaria holoendemic areas, further refining our understanding of eBL etiology

Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Down-Regulates IL-22R1 Expression through a Cis-Acting Element within the Promoter Region

Kaposi's sarcoma-associated herpesvirus (KSHV) is considered to be a necessary, but not sufficient, causal agent of Kaposi's sarcoma (KS). All forms of KS are characterized by the proliferation of spindle-shaped cells, and most (>90%) spindle cells from KS lesions are latently infected with KSHV. During KSHV latency, only a few viral genes are expressed. Among those latent genes, the ORF 73 gene encodes the latency-associated nuclear antigen (LANA), which is critical for the establishment and maintenance of the latent KSHV infection. Much evidence suggests that many cytokines can increase the frequency and aggressiveness of KS. In this study, a microarray analysis of KS and normal tissues revealed that multiple cytokines and cytokine receptors are regulated by KSHV latent infection. Of special interest, IL-22R1 transcript level was found to be down-regulated in the KS tissue. To study the possible regulation of IL-22R1 by LANA, the IL-22R1 promoter was constructed and found to contain a LANA-binding site (LBS). LANA was demonstrated to down-regulate IL-22R1 expression via direct binding to the LBS located within the IL-22R1 promoter region. Furthermore, KSHV latently infected cells showed an impaired response to IL-22 stimulation. These results suggest that LANA can regulate host factor expression by directly binding to a cis-acting element within the factor's promoter to benefit latent viral infection and suppression of the antiviral immune response