Innovative teaching of IC design and manufacture using the Superchip platform

In this paper we describe how an intelligent chip architecture has allowed a large cohort of undergraduate students to be given effective practical insight into IC design by designing and manufacturing their own ICs. To achieve this, an efficient chip architecture, the “Superchip”, has been developed, which allows multiple student designs to be fabricated on a single IC, and encapsulated in a standard package without excessive cost in terms of time or resources. We demonstrate how the practical process has been tightly coupled with theoretical aspects of the degree course and how transferable skills are incorporated into the design exercise. Furthermore, the students are introduced at an early stage to the key concepts of team working, exposure to real deadlines and collaborative report writing. This paper provides details of the teaching rationale, design exercise overview, design process, chip architecture and test regime

Allosteric Modulators of Steroid Hormone Receptors : Structural Dynamics and Gene Regulation

Peer reviewedPublisher PD

From bits to bites: Advancement of the Germinate platform to support prebreeding informatics for crop wild relatives

Management and distribution of experimental data from prebreeding projects is important to ensure uptake of germplasm into breeding and research programs. Being able to access and share this data in standard formats is essential. The adoption of a common informatics platform for crops that may have limited resources brings economies of scale, allowing common informatics components to be used across multiple species. The close integration of such a platform with commonly used breeding software, visualization, and analysis tools reduces the barrier for entry to researchers and provides a common framework to facilitate collaborations and data sharing. This work presents significant updates to the Germinate platform and highlights its value in distributing prebreeding data for 14 crops as part of the project ‘Adapting Agriculture to Climate Change: Collecting, Protecting and Preparing Crop Wild Relatives’ (hereafter Crop Trust Crop Wild Relatives project) led by the Crop Trust (https://www.cwrdiversity.org). The addition of data on these species compliments data already publicly available in Germinate. We present a suite of updated Germinate features using examples from these crop species and their wild relatives. The use of Germinate within the Crop TrustCropWildRelatives project demonstrates the usefulness of the system and the benefits a shared informatics platform provides. These data resources provide a foundation on which breeding and research communities can develop additional online resources for their crops, harness new data as it becomes available, and benefit collectively from future developments of the Germinate platform

Epithelial-to-mesenchymal transition supports ovarian carcinosarcoma tumorigenesis and confers sensitivity to microtubule-targeting with eribulin

Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analysed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumours. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts (PDX). Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a down-regulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8+ T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate EMT plays a key role in OCS tumourigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes

Investigation of SARS-CoV-2 faecal shedding in the community: a prospective household cohort study (COVID-LIV) in the UK

Background SARS-CoV-2 is frequently shed in the stool of patients hospitalised with COVID-19. The extent of faecal shedding of SARS-CoV-2 among individuals in the community, and its potential to contribute to spread of disease, is unknown. Methods In this prospective, observational cohort study among households in Liverpool, UK, participants underwent weekly nasal/throat swabbing to detect SARS-CoV-2 virus, over a 12-week period from enrolment starting July 2020. Participants that tested positive for SARS-CoV-2 were asked to provide a stool sample three and 14 days later. In addition, in October and November 2020, during a period of high community transmission, stool sampling was undertaken to determine the prevalence of SARS-CoV-2 faecal shedding among all study participants. SARS-CoV-2 RNA was detected using Real-Time PCR. Results A total of 434 participants from 176 households were enrolled. Eighteen participants (4.2%: 95% confidence interval [CI] 2.5–6.5%) tested positive for SARS-CoV-2 virus on nasal/throat swabs and of these, 3/17 (18%: 95% CI 4–43%) had SARS-CoV-2 detected in stool. Two of three participants demonstrated ongoing faecal shedding of SARS-CoV-2, without gastrointestinal symptoms, after testing negative for SARS-CoV-2 in respiratory samples. Among 165/434 participants without SARS-CoV-2 infection and who took part in the prevalence study, none had SARS-CoV-2 in stool. There was no demonstrable household transmission of SARS-CoV-2 among households containing a participant with faecal shedding. Conclusions Faecal shedding of SARS-CoV-2 occurred among community participants with confirmed SARS-CoV-2 infection. However, during a period of high community transmission, faecal shedding of SARS-CoV-2 was not detected among participants without SARS-CoV-2 infection. It is unlikely that the faecal-oral route plays a significant role in household and community transmission of SARS-CoV-2

The Superchip: Innovative Teaching of IC Design and Manufacture

In this paper we describe how through intelligent chip architecture, a large cohort (~100 students) of undergraduates can be given effective practical insight into IC design by designing and manufacturing their own individual ICs. To achieve this, the “Superchip” has been developed, which allows (without excessive cost in terms of time or resources) multiple student designs to be fabricated on a single IC, and encapsulated in a standard package. We demonstrate how the practical process has been tightly coupled with theoretical aspects of the degree course and how transferable skills are incorporated into the design exercise. The paper provides details of the chip architecture, test regime, test vectors, and an example design

IC Design and Manufacture for Undergraduates: Theory, Design and Practice

In this paper we describe how the practical design and manufacture of modern CMOS integrated circuits (ICs) have been incorporated into the second year of our undergraduate Electronics degree program. While many undergraduate degree programs offer theoretical and design of ICs, none have published a complete design cycle teaching approach including practical manufacture and test of ICs. We demonstrate how the design process has been tightly coupled with theoretical aspects of the degree course and incorporate transferable skills into the design exercise. We will also provide the technical information on how this design exercise can be accomplished sensibly for a large cohort of students (~100) in practical terms

Innovative Teaching of IC Design and Manufacture Using the Superchip Platform

In this paper we describe how an intelligent chip architecture has allowed a large cohort of undergraduate students to be given effective practical insight into IC design by designing and manufacturing their own ICs. To achieve this, an efficient chip architecture, the “Superchip”, has been developed, which allows multiple student designs to be fabricated on a single IC, and encapsulated in a standard package without excessive cost in terms of time or resources. We demonstrate how the practical process has been tightly coupled with theoretical aspects of the degree course and how transferable skills are incorporated into the design exercise. Furthermore, the students are introduced at an early stage to the key concepts of team working, exposure to real deadlines and collaborative report writing. This paper provides details of the teaching rationale, design exercise overview, design process, chip architecture and test regime

Neuraminidase Inhibitor Resistance after Oseltamivir Treatment of Acute Influenza A and B in Children

Background.Oseltamivir, a specific influenza neuraminidase inhibitor, is an effective treatment for seasonal influenza. Emergence of drug‐resistant influenza viruses after treatment has been reported, particularly in children in Japan, where the dosing schedule is different from that used throughout the rest of the world. We investigated the emergence of drug‐resistant infection in children treated with a tiered weight‐based dosing regimen. Methods.We analyzed sequential clinical nasopharyngeal samples, obtained before and after tiered weight‐based oseltamivir therapy, from children with acute influenza during 2005–2007. We isolated viruses, tested for drug resistance with use of a fluorescence‐based neuraminidase inhibition assay, performed neuraminidase gene sequencing, and determined quantitative viral loads. Results.Sixty‐four children (34 with influenza A subtype H3N2, 11 with influenza A subtype H1N1, and 19 with influenza B virus) aged 1–12 years (median age, 3 years, 1 month) were enrolled. By days 4–7 after initiation of treatment, of 64 samples tested, 47 (73.4%) and 26 (40.6%) had virus detectable by reverse‐transcriptase polymerase chain reaction and culture, respectively. By days 8–12 after initiation of treatment, of 53 samples tested, 18 (33.9%) and 1 (1.8%) had virus detectable by reverse‐transcriptase polymerase chain reaction and culture, respectively. We found no statistically significant differences in the reduction of viral shedding or time to clearance of virus between viral subtypes. Antiviral‐resistant viruses were recovered from 3 (27.3%) of 11 children with influenza A subtype H1N1, 1 (2.9%) of 34 children with influenza A subtype H3N2, and 0 (0%) of 19 children with influenza B virus, all of whom were treated with oseltamivir ( ) There was no evidence of prolonged illness in children infected with drug‐resistant virus. Conclusions.Drug resistance emerges at a higher rate in influenza A subtype H1N1 virus than in influenza A subtype H3N2 or influenza B virus after tiered weight‐based oseltamivir therapy. Virological surveillance for patterns of drug resistance is essential for determination of antiviral treatment strategies and for composition of pandemic preparedness stockpiles