Wafer-scale integration of semiconductor memory.

This work is directed towards a study of full-slice or "wafer-scale integrated" - semiconductor memory. Previous approaches to full slice technology are studied and critically compared. It is shown that a fault-tolerant, fixed-interconnection approach offers many advantages; such a technique forms the basis of the experimental work. The disadvantages of the conventional technology are reviewed to illustrate the potential improvements in cost, packing density and reliability obtainable with wafer-scale integration (W.S.l). Iterative chip arrays are modelled by a pseudorandom fault distribution; algorithms to control the linking of adjacent good - chips into linear chains are proposed and investigated by computer simulation. It is demonstrated that long chains may be produced at practicable yield levels. The on-chip control circuitry and the external control electronics required to implement one particular algorithm are described in relation to a TTL simulation of an array of 4 X 4 integrated circuit chips. A layout of the on-chip control logic is shown to require (in 40 dynamic MOS circuitry) an area equivalent to ~250 shift register stages -a reasonable overhead on large memories. Structures are proposed to extend the fixed-interconnection, fault-tolerant concept to parallel/serial organised memory - covering RAM, ROM and Associative Memory applications requiring up to~ 2M bits of storage. Potential problem areas in implementing W.S.I are discussed and it is concluded that current technology is capable of manufacturing such devices. A detailed cost comparison of the conventional and W.S.I approaches to large serial memories illustrates the potential savings available with wafer-scale integration. The problem of gaining industrial acceptance for W.S.I is discussed in relation to known and anticipated views- of new technology. The thesis concludes with suggestions for further work in the general field of wafer-scale integration

C11orf70 Mutations Disrupting the Intraflagellar Transport-Dependent Assembly of Multiple Axonemal Dyneins Cause Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disorder characterized by destructive respiratory disease and laterality abnormalities due to randomized left-right body asymmetry. PCD is mostly caused by mutations affecting the core axoneme structure of motile cilia that is essential for movement. Genes that cause PCD when mutated include a group that encode proteins essential for the assembly of the ciliary dynein motors and the active transport process that delivers them from their cytoplasmic assembly site into the axoneme. We screened a cohort of affected individuals for disease-causing mutations using a targeted next generation sequencing panel and identified two unrelated families (three affected children) with mutations in the uncharacterized C11orf70 gene (official gene name CFAP300). The affected children share a consistent PCD phenotype from early life with laterality defects and immotile respiratory cilia displaying combined loss of inner and outer dynein arms (IDA+ODA). Phylogenetic analysis shows C11orf70 is highly conserved, distributed across species similarly to proteins involved in the intraflagellar transport (IFT)-dependant assembly of axonemal dyneins. Paramecium C11orf70 RNAi knockdown led to combined loss of ciliary IDA+ODA with reduced cilia beating and swim velocity. Tagged C11orf70 in Paramecium and Chlamydomonas localizes mainly in the cytoplasm with a small amount in the ciliary component. IFT139/TTC21B (IFT-A protein) and FLA10 (IFT kinesin) depletion experiments show that its transport within cilia is IFT dependent. During ciliogenesis, C11orf70 accumulates at the ciliary tips in a similar distribution to the IFT-B protein IFT46. In summary, C11orf70 is essential for assembly of dynein arms and C11orf70 mutations cause defective cilia motility and PCD

Phylogenomics of non-model ciliates based on transcriptomic analyses

© The Author(s) 2015. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. The attached file is the published version of the article

Mutations in Outer Dynein Arm Heavy Chain DNAH9 Cause Motile Cilia Defects and Situs Inversus

International audienceMotile cilia move body fluids and gametes and the beating of cilia lining the airway epithelial surfaces ensures that they are kept clear and protected from inhaled pathogens and consequent respiratory infections. Dynein motor proteins provide mechanical force for cilia beating. Dynein mutations are a common cause of primary ciliary dyskinesia (PCD), an inherited condition characterized by deficient mucociliary clearance and chronic respiratory disease coupled with laterality disturbances and subfertility. Using next-generation sequencing, we detected mutations in the ciliary outer dynein arm (ODA) heavy chain gene DNAH9 in individuals from PCD clinics with situs inversus and in one case male infertility. DNAH9 and its partner heavy chain DNAH5 localize to type 2 ODAs of the distal cilium and in DNAH9-mutated nasal respiratory epithelial cilia we found a loss of DNAH9/DNAH5-containing type 2 ODAs that was restricted to the distal cilia region. This confers a reduced beating frequency with a subtle beating pattern defect affecting the motility of the distal cilia portion. 3D electron tomography ultrastructural studies confirmed regional loss of ODAs from the distal cilium, manifesting as either loss of whole ODA or partial loss of ODA volume. Paramecium DNAH9 knockdown confirms an evolutionarily conserved function for DNAH9 in cilia motility and ODA stability. We find that DNAH9 is widely expressed in the airways, despite DNAH9 mutations appearing to confer symptoms restricted to the upper respiratory tract. In summary, DNAH9 mutations reduce cilia function but some respiratory mucociliary clearance potential may be retained, widening the PCD disease spectrum

Action learning in schools: Reframing teachers' professional learning and development

© 2009 Peter Aubusson, Robyn Ewing and Garry Hoban. Teaching is becoming increasingly complex in the 21st Century, creating a need for more sophisticated frameworks to support teachers’ professional learning. Action learning is one such framework and has been used for workplace learning in business settings for many years. It is now becoming increasingly popular in school and university settings, but it is often misunderstood. This book clarifies what action learning is, linking key concepts to illustrate that it is not merely a process, but a dynamic interaction between professional learning, communities, leadership and change. The book brings together more than a decade of the authors’ research in school-based action learning.Rich and diverse, the research draws on more than 100 case studies of action learning by teams of teachers in schools. The authors:• provide practical advice on how to initiate and sustain action learning;• explain the interaction between action learning, teacher development, professional learning, community building, leadership and change; and• illustrate how action learning can link to classroom practice so closely that it becomes part of what teachers do, rather than an added impost.Addressing the highs and lows, the successes and failures, and their underlying causes, Action Learning in Schools provides insights into theories of cooperation, innovation, leadership and community formation to inform individual projects and large-scale school improvement initiatives. It will be of interest to teacher educators, pre-service and experienced teachers alike, as well as school and education system managers and policymakers keen to enhance teacher professional learning and educational outcomes for students