A GLI1-p53 inhibitory loop controls neural stem cell and tumour cell numbers

How cell numbers are determined is not understood. Hedgehog-Gli activity is involved in precursor cell proliferation and stem cell self-renewal, and its deregulation sustains the growth of many human tumours. However, it is not known whether GLI1, the final mediator of Hh signals, controls stem cell numbers, and how its activity is restricted to curtail tumourigenesis. Here we have altered the levels of GLI1 and p53, the major tumour suppressor, in multiple systems. We show that GLI1 expression in Nestin+ neural progenitors increases precursor and clonogenic stem cell numbers in vivo and in vitro. In contrast, p53 inhibits GLI1-driven neural stem cell self-renewal, tumour growth and proliferation. Mechanistically, p53 inhibits the activity, nuclear localisation and levels of GLI1 and in turn, GLI1 represses p53, establishing an inhibitory loop. We also find that p53 regulates the phosphorylation of a novel N' truncated putative activator isoform of GLI1 in human cells. The balance of GLI1 and p53 functions, thus, determines cell numbers, and prevalence of p53 restricts GLI1-driven stem cell expansion and tumourigenesis

First Results from the rapid-response spectrophotometric characterization of Near-Earth Objects

As part of our multi-observatory, multi-filter campaign, we present \rmi color observations of 82 Near-Earth Objects (NEOs) obtained with the RATIR instrument on the 1.5m robotic telescope at the San Pedro Martir's National Observatory in Mexico. Our project is particularly focused on rapid response observations of small ($\lesssim 850$ m) NEOs. The rapid response and the use of spectrophotometry allows us to constrain the taxonomic classification of NEOs with high efficiency. Here we present the methodology of our observations and our result, suggesting that the ratio of C-type to S-type asteroids in a size range of $\sim$30-850m is 1.1, which is in accordance with our previous results. We also find that 10$\%$ of all NEOs in our sample are neither C- nor S-type asteroidsComment: 31 pages, 4 tables, 10 figure

School-Based Juvenile Probation and Police Partnerships for Truancy Reduction

Truancy places students at risk in primary and secondary education and is linked to conduct disorder, drug use, and delinquency. To prevent truancy and reduce risk, school-based proba-tion supervision has emerged within school districts in partnership with local law enforcement officers in an effort to enforce probation conditions for truant youths and prevent future delin-quency. This research uses key information interviews of knowledgeable stakeholders to examine the delivery of school-based probation supervision. Home visits and court hearings were perceived to be effective at reducing truancy and tardiness. This study affirms that strong lead-ership, information sharing, and involvement of parents were 3 key factors related to truancy reduction

AMASS: A Large-Scale European Project to Improve the Assurance and Certification of Cyber-Physical Systems

Most safety-critical systems must undergo assurance and certification processes. The associated activities can be complex and labour-intensive, thus practitioners need suitable means to execute them. The activities are further becoming more challenging as a result of the evolution of the systems towards cyber-physical ones, as these systems have new assurance and certification needs. The AMASS project (Architecture-driven, Multi-concern and Seamless Assurance and Certification of Cyber-Physical Systems) tackled these issues by creating and consolidating the de-facto European-wide open tool platform, ecosystem, and self-sustainable community for assurance and certification of cyber-physical systems. The project defined a novel holistic approach for architecture-driven assurance, multi-concern assurance, seamless interoperability, and cross- and intra-domain reuse of assurance assets. AMASS results were applied in 11 industrial case studies to demonstrate the reduction of effort in assurance and certification, the reduction of (re)certification cost, the reduction of assurance and certification risks, and the increase in technology harmonisation and interoperability.The research leading to this paper has received funding from the AMASS project (H2020-ECSEL grant agreement no 692474; Spain’s MINECO ref. PCIN-2015-262; Sweden’s Vinnova) and the Ramon y Cajal Program (Spain’s MICINN ref. RYC-2017-22836; EC’s European Social Fund). We are also grateful to all the AMASS partners. Their work and results are summarised in this paper

Architecture-driven, Multi-concern and Seamless Assurance and Certification of Cyber-Physical Systems.

Unlike practices in electrical and mechanical equipment engineering, Cyber-Physical Systems (CPS) do not have a set of standardized and harmonized practices for assurance and certification that ensures safe, secure and reliable operation with typical software and hardware architectures. This paper presents a recent initiative called AMASS (Architecture-driven, Multi-concern and Seamless Assurance and Certification of Cyber-Physical Systems) to promote harmonization, reuse and automation of labour-intensive certification-oriented activities via using model-based approaches and incremental techniques. AMASS will develop an integrated and holistic approach, a supporting tool ecosystem and a self-sustainable community for assurance and certification of CPS. The approach will be driven by architectural decisions (fully compatible with standards, e.g. AUTOSAR and IMA), including multiple assurance concerns such as safety, security and reliability. AMASS will support seamless interoperability between assurance/certification and engineering activities along with third-party activities (external assessments, supplier assurance). The ultimate aim is to lower certification costs in face of rapidly changing product features and market needs.This project has received funding from the Electronic Component Systems for European Leadership Joint Undertaking under grant agreement No 692474. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and Spain, Czech Republic, Germany, Sweden, Austria, Italy, United Kingdom, Franc

Sputter-deposited fuel cell membranes and electrodes

A method for preparing a membrane for use in a fuel cell membrane electrode assembly includes the steps of providing an electrolyte membrane, and sputter-depositing a catalyst onto the electrolyte membrane. The sputter-deposited catalyst may be applied to multiple sides of the electrolyte membrane. A method for forming an electrode for use in a fuel cell membrane electrode assembly includes the steps of obtaining a catalyst, obtaining a backing, and sputter-depositing the catalyst onto the backing. The membranes and electrodes are useful for assembling fuel cells that include an anode electrode, a cathode electrode, a fuel supply, and an electrolyte membrane, wherein the electrolyte membrane includes a sputter-deposited catalyst, and the sputter-deposited catalyst is effective for sustaining a voltage across a membrane electrode assembly in the fuel cell

New evidence for super-roughening in crystalline surfaces with disordered substrate

We study the behavior of the Binder cumulant related to long distance correlation functions of the discrete Gaussian model of disordered substrate crystalline surfaces. We exhibit numerical evidence that the non-Gaussian behavior in the low-$T$ region persists on large length scales, in agreement with the broken phase being super-rough.Comment: 10 pages and 4 figures, available at http://chimera.roma1.infn.it/index_papers_complex.html . We have extended the RG discussion and minor changes in the tex

Error estimation in environmental DNA targets quantification due to PCR efficiencies differences between real samples and standards

Postprint (published version