Managing the Enriched Experience Network - Learning-Outcome Approach to the Experimental Design Life-Cycle

Experimental design methods have long been used in scientific areas such as agriculture, biology and physics to minimise error and assure validity. Although most network researchers performing experiments with testbeds and simulations implicitly follow scientific method, until recently there has been little emphasis on improving experimental design methods. Traditional experimental design focuses on experiments where the scope and objectives are relatively constrained, however network research in innovative areas where there is little or no precedence often has changing objectives that evolve over time. We describe the learning-outcome approach to the experimental design life-cycle that applies the concepts of systems development life-cycle models used in software engineering, as well as learning taxonomies used in education. Our approach extends traditional experimental design by providing a more comprehensive and efficient way of decomposing an experimental research project into manageable stages that are designed rather than improvised, leading to a well-structured way of assessing the knowledge gained. We provide an insight into our experiences with this approach in the context of experimental research in management of Alcatel Australia's new-generation Enriched Experience Network

Dairying, diseases and the evolution of lactase persistence in Europe

Update notice Author Correction: Dairying, diseases and the evolution of lactase persistence in Europe (Nature, (2022), 608, 7922, (336-345), 10.1038/s41586-022-05010-7) Nature, Volume 609, Issue 7927, Pages E9, 15 September 2022In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years(1). Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions(2,3). Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectoriesthan uniform selection since the Neolithic period. In the UK Biobank(4,5) cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

A Distributed Policy-based Network Management (PBNM) System for Enriched Experience Networks™ (EENs)

AND CONCRETE POLICIES. SOURCE: [1] ....................................... 1 TABLE 2 -- RESEARCH PROCESS AND METHODS......................................................................................... 1 TABLE 3 -- COMPLETION PLAN (PER SEMESTER)........................................................................................ 1 TABLE 4 -- THESIS STRUCTURE.................................................................................................................. 1 Nigel Sheridan-Smith iii v1.0, 3/11/2003 NOTICE OF DOCTORAL ASSESSMENT SEMINAR Information and Communication Group Faculty of Engineering University of Technology, Sydney Title: A Distributed Policy-based Network Management (PBNM) system for Enriched Experience Networks^TM (EENs) Doctoral Candidate: Nigel Sheridan-Smith Venue: 1/2219 Time: 10:30 am Date: Wednesday 5 November 2003 ABSTRACT Policy-based Network Management (PBNM) systems have traditionally been used in enterprise networks where the emphasis has been on centralising the responsibility for management of the network for simplicity. In this environment, PBNM systems have been helpful in partially automating the configuration of the network and prioritising the use of resources

Strongly typed Architectural Models for Architecture-based Engineering: Current developments in their definition and description

It is the UTS A-Engineering group’s position that a strongly typed architectural model is the central and fundamental concept in the model-based development or alternatively the architecture-based engineering of computer based systems. Given a standard architectural model and representation, the architecture of systems can be discussed, drawn, reasoned about and classified. This paper presents the current UTS definitions and descriptions of system architecture. The definitions and concepts provided herein have been used as the foundation of several real-world model-based development, design, evolution and engineering projects

Application of penetrators within the solar system

About the book: This invaluable volume set of Advances in Geosciences continues the excellent tradition of the Asia-Oceania scientific community in providing the most up-to-date research results on a wide range of geosciences and environmental science. The information is vital to the understanding of the effects of climate change, extreme weathers on the most populated regions and fastest moving economies in the world. Besides, these volumes also highlight original papers from many prestigious research institutions which are doing cutting edge study in atmospheric physics, hydrological science and water resource, ocean science and coastal study, planetary exploration and solar system science, seismology, tsunamis, upper atmospheric physics and space science