Expression kinetics and innate immune response after electroporation and LNP-mediated delivery of a self-amplifying mRNA in the skin

In this work, we studied the expression kinetics and innate immune response of a self-amplifying mRNA (sa-RNA) after electroporation and lipid-nanoparticle (LNP)-mediated delivery in the skin of mice. Intradermal electroporation of the sa-RNA resulted in a plateau-shaped expression, with the plateau between day 3 and day 10. The overall protein expression of sa-RNA was significantly higher than that obtained after electroporation of plasmid DNA (pDNA) or non-replication mRNAs. Moreover, using IFN-beta reporter mice, we elucidated that intradermal electroporation of sa-RNA induced a short-lived moderate innate immune response, which did not affect the expression of the sa-RNA. A completely different expression profile and innate immune response were observed when LNPs were used. The expression peaked 24 h after intradermal injection of sa-RNA-LNPs and subsequently showed a sharp drop. This drop might be explained by a translational blockage caused by the strong innate immune response that we observed in IFN-beta reporter mice shortly (4 h) after intradermal injection of sa-RNA-LNPs. A final interesting observation was the capacity of sa-RNA-LNPs to transfect the draining lymph nodes after intradermal injection

The end of jobs for life?: corporate employment systems: Japan and elsewhere

"It is not only in Japan that traditional employment systems are being called into question. It has become conventional wisdom on the OECD conference circuit that we are entering a new era of intensified global competition in which only the most and quot;flexible" firms can survive. ''Flexibility'' and the elimination of rigidities, particularly labour market rigidities, became, in the mid-1980s, the keynote of prescriptions both for lack of competitiveness and for rising unemployment. Even earlier reservations about the desirability of preserving a "core" of stable, long-serving, committed workers, differentiated from a flexible "periphery" have given way to prescriptions for wholesale ''down-sizing.'' There is a flexibility trade off. Concern with labour market flexibility -- especially managers'' ability to hire and fire at will -- is strengthened in the Anglo-Saxon economies by the inflexibility of the financial markets they face. Japanese firms, being more insulated from the short-term demands of shareholders, have hitherto been able to afford more ''rigid'' employment systems from which they gain the advantage of employee commitment and cooperative and flexible attitudes to work. But today the competitiveness/flexibility concern grows in Japan too. The lifetime employment/seniority-constrained pay and promotion system is under attack. Advocacy of change is common; assertions that wholesale change has already taken place almost equally common. The reasons are to be found partly in the objective situations of many firms after four years of recession, partly in a loss of self-confidence and a ''resurgence of the American model.'' Actual change seems in fact to be marginal, but there are a number of grounds for expecting change in the future: value change -- greater affluence, diminished work ethic, and diminished egalitarianism; the possible resurgence of shareholder power; the declining influence of unions; the declining ''intellectual quality'' of blue-collar and routine white-collar workers; increased inter-firm competition and the reduction of industry cartel understandings; slower growth; low wage competition, particularly in future from China, and the "hollowing-out" response thereto. Those who have a stake in Japan''s "employee sovereignty" jimponshugi, and would be reluctant to see it slide into just another version of "shareholder sovereignty" Anglo-Saxon capitalism, might be expected to be proposing legislation to bring company law in line with current Japanese reality. No one seems to be doing so.

Evaluating the Weekly-Assessed Tutorial Sheet approach to assessment: background, pedagogy and impact

This paper presents the results of using student-unique, weekly-assessed tasks to overcome a low examination performance in a first-year engineering module. In this instance, the weekly assessment tasks were created by off-the-shelf and bespoke software to form an integrated computer-assisted assessment (CAA) programme. This programme set, delivered, collected, marked and provided prompt feedback on the students’ work. The CAA was a set of student-unique Weekly-Assessed Tutorial Sheets (WATS). The rationale for the modified assessment strategy is presented together with the examination performance figures before and after the introduction of WATS.Peer reviewe

Accelerated Neural Networks on OpenCL Devices Using SYCL-DNN

Over the past few years machine learning has seen a renewed explosion of interest, following a number of studies showing the effectiveness of neural networks in a range of tasks which had previously been considered incredibly hard. Neural networks' effectiveness in the fields of image recognition and natural language processing stems primarily from the vast amounts of data available to companies and researchers, coupled with the huge amounts of compute power available in modern accelerators such as GPUs, FPGAs and ASICs. There are a number of approaches available to developers for utilizing GPGPU technologies such as SYCL, OpenCL and CUDA, however many applications require the same low level mathematical routines. Libraries dedicated to accelerating these common routines allow developers to easily make full use of the available hardware without requiring low level knowledge of the hardware themselves, however such libraries are often provided by hardware manufacturers for specific hardware such as cuDNN for Nvidia hardware or MIOpen for AMD hardware. SYCL-DNN is a new open-source library dedicated to providing accelerated routines for neural network operations which are hardware and vendor agnostic. Built on top of the SYCL open standard and written entirely in standard C++, SYCL-DNN allows a user to easily accelerate neural network code for a wide range of hardware using a modern C++ interface. The library is tested on AMD's OpenCL for GPU, Intel's OpenCL for CPU and GPU, ARM's OpenCL for Mali GPUs as well as ComputeAorta's OpenCL for R-Car CV engine and host CPU. In this talk we will present performance figures for SYCL-DNN on this range of hardware, and discuss how high performance was achieved on such a varied set of accelerators with such different hardware features.Comment: 4 pages, 3 figures. In International Workshop on OpenCL (IWOCL '19), May 13-15, 2019, Bosto

Limits to Modularity: A Review of the Literature and Evidence from Chip Design

This working paper has been prepared as part of the East-West Center's research project on Globalization of Knowledge Work: Why is Chip Design Moving to Asia. In this paper, Dieter assesses what we know about the limits to modularity and their impact on firm organization and industry structure. He focuses on evidence form chip design, drawing on interview on 2002 and 2003 with a sample of 60 companies and 15 research institutions that are involved in chip design in the US, Taiwan, Korea, China and Malaysia. It is summarized "stylized" propositions of the modularity literature that are well-established, as well as predictions that are controversial. In addition, important limits to modularity and relevant management responses were reviewed.