FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity

Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and Wegener's granulomatosis in two independent cohorts from the UK (P = 3 x 10(-3)) and France (P = 1.1 x 10(-4)). We did not observe this association in the organ-specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity.     

<Emphasis Type="Bold">An Engineering View for Social Systems: Agency as an Operational Principle for Designing Higher Education Access Policies</Emphasis>

Access to higher education (HE) has been a persistent concern for governments, practitioners and researchers. Access to HE has been widely studied from scientific perspectives that have focussed on the factors that contribute to the problem; however, authors have highlighted the need for systemic and design perspectives on education systems. The need to connect research with policy remains one of the most challenging issues for education researchers. In view of this gap, this paper argues that engineering thinking and methods represent an opportunity for the design of HE access policies because engineering rationality (distinct from scientific rationalities) matches the concerns and goals of any policymaking attempt. Engineers design artefacts to meet particular goals. These artefacts are artificial systems, tangible or intangible, such as hammers, bridges or whole organizations, which are designed in particular contexts to meet precise goals. Policies for access to HE are good examples of artefacts that seek to fulfil specific needs under concrete constraints inherent to a country or region. More specifically, HE systems are social systems; in other words, they are created and recreated by the interactions and decisions of diverse actors. Hence, to change, redesign or improve such types of systems involves engineering their very interactions that are the outcomes of institutional and human actions. In particular, engineering design requires operational principles. Thus, we propose agency as a fundamental design concept for the improvement of HE systems, which opens new possibilities for a distinct type of policy-making that takes excellent advantage of what engineering can offer, while at the same time expanding on traditional expectations for engineering.     

A Systemic Framework to Develop Sustainable Engineering Solutions in Rural Communities in Colombia

In several rural areas in Colombia there is a serious lack of water quality supply. Thereby the problematic situation is understood as complex one that involves stakeholders with pluralistic interests, multiple variables and requires the development of sustainable and suitable solutions. In order to address this issue, this paper proposes an integration of engineering design framework (CDIO) with a systemic approach. Particularly the approach emphasizes on systemic elements such as autonomy, systems within systems, cooperation between stakeholders and cause effect relations; it also proposes a previous observing phase for engineering design framework. Thus the proposed systemic framework aims to generate projects that improve living conditions in rural communities and promote the production of knowledge between the stakeholders to ensure sustainability in the long term. To illustrate the proposal, this work contains a case study that discusses a project carried out by a research team—Ingenieros Sin Fronteras Colombia—in a rural district near to Colombia’s capital. The experience, which involved and benefited 16 families in the community, provided strong evidence to support the proposed framework. The paper concludes with a discussion about the replication of this proposal in other contexts.     

Chaos-based communications at high bit rates using commercial fibre-optic links

Chaotic signals have been proposed as broadband information carriers with the potential of providing a high level of robustness and privacy in data transmission. Laboratory demonstrations of chaos-based optical communications have already shown the potential of this technology, but a field experiment using commercial optical networks has not been undertaken so far. Here we demonstrate high-speed long-distance communication based on chaos synchronization over a commercial fibre-optic channel. An optical carrier wave generated by a chaotic laser is used to encode a message for transmission over 120 km of optical fibre in the metropolitan area network of Athens, Greece. The message is decoded using an appropriate second laser which, by synchronizing with the chaotic carrier, allows for the separation of the carrier and the message. Transmission rates in the gigabit per second range are achieved, with corresponding bit-error rates below 10(-7). The system uses matched pairs of semiconductor lasers as chaotic emitters and receivers, and off-the-shelf fibre-optic telecommunication components. Our results show that information can be transmitted at high bit rates using deterministic chaos in a manner that is robust to perturbations and channel disturbances unavoidable under real-world conditions.     

A restricted cell population propagates glioblastoma growth after chemotherapy

Glioblastoma multiforme is the most common primary malignant brain tumour, with a median survival of about one year. This poor prognosis is due to therapeutic resistance and tumour recurrence after surgical removal. Precisely how recurrence occurs is unknown. Using a genetically engineered mouse model of glioma, here we identify a subset of endogenous tumour cells that are the source of new tumour cells after the drug temozolomide (TMZ) is administered to transiently arrest tumour growth. A nestin-ΔTK-IRES-GFP (Nes-ΔTK-GFP) transgene that labels quiescent subventricular zone adult neural stem cells also labels a subset of endogenous glioma tumour cells. On arrest of tumour cell proliferation with TMZ, pulse-chase experiments demonstrate a tumour re-growth cell hierarchy originating with the Nes-ΔTK-GFP transgene subpopulation. Ablation of the GFP+ cells with chronic ganciclovir administration significantly arrested tumour growth, and combined TMZ and ganciclovir treatment impeded tumour development. Thus, a relatively quiescent subset of endogenous glioma cells, with properties similar to those proposed for cancer stem cells, is responsible for sustaining long-term tumour growth through the production of transient populations of highly proliferative cells.     

An array of possibilities for the study of autoimmunity

Since the completion of the sequencing of the human genome, scientific focus has shifted from studying genes to analysing the much larger number of proteins encoded by them. Several proteins can be generated from a single gene depending on how the genetic information is read (transcribed) and how the resultant protein is modified following translation (post-translational modification). Genomic and proteomic technologies are already providing useful information about autoimmune disease, and they are likely to lead to important discoveries within the next decade.