Targeting Cancer with CRISPR/Cas9-Based Therapy

Cancer is a devastating condition characterised by the uncontrolled division of cells with many forms remaining resistant to current treatment. A hallmark of cancer is the gradual accumulation of somatic mutations which drive tumorigenesis in cancerous cells, creating a mutation landscape distinctive to a cancer type, an individual patient or even a single tumour lesion. Gene editing with CRISPR/Cas9-based tools now enables the precise and permanent targeting of mutations and offers an opportunity to harness this technology to target oncogenic mutations. However, the development of safe and effective gene editing therapies for cancer relies on careful design to spare normal cells and avoid introducing other mutations. This article aims to describe recent advancements in cancer-selective treatments based on the CRISPR/Cas9 system, especially focusing on strategies for targeted delivery of the CRISPR/Cas9 machinery to affected cells, controlling Cas9 expression in tissues of interest and disrupting cancer-specific genes to result in selective death of malignant cells.

Security Analysis of Machine Learning-Based PUF Enrollment Protocols: A Review

The demand for Internet of Things services is increasing exponentially, and consequently a large number of devices are being deployed. To efficiently authenticate these objects, the use of physical unclonable functions (PUFs) has been introduced as a promising solution for the resource-constrained nature of these devices. The use of machine learning PUF models has been recently proposed to authenticate the IoT objects while reducing the storage space requirement for each device. Nonetheless, the use of a mathematically clonable PUFs requires careful design of the enrollment process. Furthermore, the secrecy of the machine learning models used for PUFs and the scenario of leakage of sensitive information to an adversary due to an insider threat within the organization have not been discussed. In this paper, we review the state-of-the-art model-based PUF enrollment protocols. We identity two architectures of enrollment protocols based on the participating entities and the building blocks that are relevant to the security of the authentication procedure. In addition, we discuss their respective weaknesses with respect to insider and outsider threats. Our work serves as a comprehensive overview of the ML PUF-based methods and provides design guidelines for future enrollment protocol designers.

Measuring the experience of remote home workers: A scoping review

Introduction: Working from home (WFH) remotely is a modality of working that requires the careful design of systems of rules and tools to enable people to exchange information and perform actions. WFH is expected to expand after the COVID-19 pandemic, and how best to reliably assess and compare the experience of workers with different (sociotechnical) systems of WFH is central to the diffusion of acceptable modalities of remote working. However, the concept of experience and how it can be measured in the domain in WFH is yet to be clearly characterized.Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology for scoping reviews, we systematically map the approaches used by researchers to assess WFH, identify which aspects are usually investigated, and examine how such aspects are usually measured in terms of questions and tools. Literature is collected using Scopus and Web of Science.Results: Thirty-four records out of 323 focusing either on validating a scale, presenting theoretically the experience of workers or testing this empirically are included in the qualitative synthesis. The results highlight a lack of unified terminology and tools, with assessments of workers’ experience mainly characterized by survey approaches and qualitative questions. Conclusion: Clustering together the most investigated aspects in the literature and reviewing how these aspects are assessed, we propose a list of 10 relevant overarching dimensions and attempt to define workers’ experience in the domain of WFH remotely. This definition can be used as a tool by researchers aiming to assess the experience of workers in order to inform the design or redesign of the sociotechnical systems that enable WFH.

Exploring Efficient Architectures on Remote In-Memory NVM over RDMA

Efficiently accessing remote file data remains a challenging problem for data processing systems. Development of technologies in non-volatile dual in-line memory modules (NVDIMMs), in-memory file systems, and RDMA networks provide new opportunities towards solving the problem of remote data access. A general understanding about NVDIMMs, such as Intel Optane DC Persistent Memory (DCPM), is that they expand main memory capacity with a cost of multiple times lower performance than DRAM. With an in-depth exploration presented in this paper, however, we show an interesting finding that the potential of NVDIMMs for high-performance, remote in-memory accesses can be revealed through careful design. We explore multiple architectural structures for accessing remote NVDIMMs in a real system using Optane DCPM, and compare the performance of various structures. Experiments are conducted to show significant performance gaps among different ways of using NVDIMMs as memory address space accessible through RDMA interface. Furthermore, we design and implement a prototype of user-level, in-memory file system, RIMFS, in the device DAX mode on Optane DCPM. By comparing against the DAX-supported Linux file system, Ext4-DAX, we show that the performance of remote reads on RIMFS over RDMA is 11.44 higher than that on a remote Ext4-DAX on average. The experimental results also show that the performance of remote accesses on RIMFS is maintained on a heavily loaded data server with CPU utilization as high as 90%, while the performance of remote reads on Ext4-DAX is significantly reduced by 49.3%, and the performance of local reads on Ext4-DAX is even more significantly reduced by 90.1%. The performance comparisons of writes exhibit the same trends.

Clinically silent LINE 1 insertion in the PNPLA3 gene may impede genotyping of the p.I148M variant

The patatin-like phospholipase domain containing 3 (PNPLA3) gene (viz. its I148M variant) is one of the key players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We have identified a novel insertion/deletion variant of 1114 bp, localized in the second intron of the PNPLA3 gene, which corresponds to the 3′ terminal sequence of the long-interspersed element (LINE-1). DNA analysis of 122 NAFLD patients and 167 control subjects as well as RNA analysis of 19 liver biopsies revealed that the novel variant is very common (frequency = 0.41), fully linked to the clinically important I148M variant, and clinically silent. Although the LINE-1 insertion does not seem to have any biological effect, it can impede genotyping of the I148M variant. If insertion prevents the attachment of the diagnostic primer, then the non-insertion allele will be selectively amplified; and thus the frequency of the 148M "risk" allele will be significantly overestimated due to the complete linkage of the LINE-1 insertion and the 148I allele of the PNPLA3 gene. Therefore, our findings underline the importance of careful design and consistent documentation of the methodology, including primer sequences. Critical revisions of the results of some studies that have already been reported may therefore be needed.

The influence of traditional Chinese landscape architecture on the image of small architectural forms in Europe

The article analyzes the influence of traditional Chinese landscape architecture on the shaping of European small architectural forms and the influence of European architecture on contemporary Chinese architectural practice. The purpose of the article is to identify the features of the architectural mutual influences of Chinese and European cultures. The method of historical analysis, the method of comparative analysis and the graphoanalytical method are used. The lack of identity between the Chinese and European gardens and the park with the pavilions is proved at the different hierarchical levels. Two groups of European Chinoiserie style pavilions have been identified: which give a false idea of Chinese architectural traditions and which represent a simplified version of those traditions. There is noticed the influence of the traditional Chinese approach to the architectural objects placement in the natural environment on the development of the contextualism concept in Western architecture (since the 1960s) which proclaims its purpose to preserve the natural beauty of the site through careful design that relates to its surroundings. The concept of contextualism is now widely used in the design of small architectural forms in the urban environment and in the design of the architectural environment in general, both in Europe and in China. This is a clear example of mutual enrichment with the ideas of two civilizations, each of which preserves its own culture.

Organizing Investigations and Surveys

Organizing investigations and surveys can be complicated and they require careful planning. Hand-held portable devices and mobile phones are commonly used today. All questionnaires require careful design, preparation, and piloting. Survey objectives can be reviewed if they are too ambitious and survey design may require changes, such as a reduction in sample size, omission of particular questions, or fewer clinical and laboratory procedures. A pilot trial is essential to test all the methods, fieldwork plans and logistic support. A full survey check list is provided.

A numerical study of plasmon-induced enhancement of dipole emission by arrays of silver nanospheres and nanoprisms

Plasmon-induced enhancement of the photoluminescence (PL) intensity of quantum emitters by plasmon nanoparticles (PNPs) is a promising approach for the design and fabrication of PL hybrid materials with improved properties for biosensing and optoelectronics applications. This enhancement can be achieved through careful selection of such parameters as the PNP’s shape, material, size, the type of the medium around them, as well as the excitation and emission wavelengths of the emitter. Here, we simulated the nano-hybrid materials based on arrays of silver nanospheres, nanoprisms, and their combinations, located on polymer films with embedded dipole emitters. For these systems, the Purcell effect, as well as the excitation enhancement, transmittance, and absorption were evaluated. The results show the way to improve the PL properties of thin hybrid films by careful design of their composition using developed models.

Enhancing online protocols through design-based research to improve cognitive presence in a large enrolment course

Instructors face challenges in facilitating higher levels of shared cognition in large enrolment classes. One strategy to foster shared cognition is the use of asynchronous discussions; however, these can be difficult to support with large numbers of students. Online protocols have been found to help students take more ownership of the discussion, reducing the workload of instructors and thus may be helpful in this context. The purpose of this study was to determine the most effective design of online protocols in large enrolment classes. The study used a design-based research methodology to iteratively design, assess and refine the online protocols and the design principles of its underlying protocol pedagogy. Participants for this study were 1,286 students enrolled in a blended undergraduate class in business that used online protocols for discussions over three semesters. The paper describes how iterative changes in the design of protocol-based discussions influenced students' cognitive presence. Students’ perceptions of cognitive presence were significantly higher in the second and third iterations, and the concepts shared by group members were significantly more integrated by the third iteration. Findings suggest that with careful design, these enhanced protocols are a potentially useful strategy to facilitate asynchronous online discussions in large classes. Implications for practice or policy: Students need additional incentives to actively participate in large enrolment courses. Instructors can use peer questioning to increase shared cognition in large enrolment courses. Instructors should create concise directions with modelling of exemplary posts to help reduce confusion. Students in large enrolment courses benefit from additional scaffolding of norms to foster a sense of trust. Design-based research provides an effective methodology to examine both theoretical and practical implications of online protocols on cognitive presence.

The Impact of COVID-19 on the Higher Education Sector: Challenges and Opportunities

The COVID-19 pandemic has provoked a sudden and disruptive shift to remote and distance learning in the Higher Education Sector. The latter encompasses many complex elements that necessitate careful design and development to endorse a productive education outcome. This short reflection discusses the impact of the pandemic on the Higher Education Sector in general, shedding the light on the main challenges and opportunities induced by the shift to online education.