Experimental tests and numerical simulations on the mechanical response of RC slabs externally strengthened by passive and prestressed FRP strips

Externally Bonded Reinforcement on Groove (EBROG) method has been introduced to enhance the bond resistance of FRP strips to concrete. It has demonstrated that EBROG generally outperforms EBR in terms of loadtransfer capacity between FRP strips and concrete. The present study aims to further demonstrate the potential of EBROG applied for flexural strengthening. A specimen reinforced according to the EBR solution and a nominally equal one reinforced through the EBROG system are first presented. Then, the performance of a newly fully-composite mechanical end anchorage for prestressed FRP strip to be used in conjunction with the EBROG method is investigated. The experimental results show that the premature debonding observed in EBR is avoided by EBROG in the case of "passive" FRP strips. Moreover, the combination of EBROG and end anchorage demonstrates their effectiveness, as the pre-stressed slab exhibits the full exploitation of the FRP up to rupture. Numerical analyses, carried out by means of a model already presented by the authors, show that the structural response of the tested slabs can be simulated in a very accurate manner if consistent assumptions are made in terms of bond-slip laws adopted to describe the interaction between FRP and concrete in EBR and EBROG

Enhancing Industry Exposure, Discovery-Based and Cooperative Learning in Mechanics of Solids

BACKGROUND Mechanics of Solids is a second year undergraduate subject, undertaken by both Civil and Mechanical engineering students at the University of Technology, Sydney (UTS). Mechanics of Solids has been delivered for many years in a traditional format with lectures and problem solving tutorials. As part of a national Australian project “Enhancing Industry Exposure in Engineering Degrees”, UTS in partnership with other universities and industry partners in Australia has sought industry involvement to engage students with the real-world challenges of engineering practice. PURPOSE The main objective of this project is to design, develop and implement learning modules in Mechanis of Solids that integrate industry exposure to provide context for the concepts included in this subject. DESIGN The project consisted of six guest lectures by industry representatives on topics related to typical Mechanics of Solids subject matter and two seminars on using MDSolids software. Students completed a collaborative assignment aligned with one of the industry presentations. Their reports and presentations were assessed on assessment criteria which included contextual understanding, judgement, effective collaboration and creativity, and their perceptions were captured to evaluate the impact of industry engagement in this subject. RESULTS One of the major benefits of this project was students’ better understanding of engineering practice. There were also positive effects on students’ motivation for learning engineering. CONCLUSIONS This paper reports the major findings, outcomes and challenges for implementing enhancing industry exposure approach in Mechanics of Solids subject at UTS. The main finding of this research concluded that this project is very valuable to both students as it promotes exposure to real-world engineering challenges. The students’ exposure to real and substantive challenges improves their contextual understanding, plus their judgement, practice based planning, teamwork, and initiative learning skills

HD-Bind: Encoding of Molecular Structure with Low Precision, Hyperdimensional Binary Representations

Publicly available collections of drug-like molecules have grown to comprise 10s of billions of possibilities in recent history due to advances in chemical synthesis. Traditional methods for identifying ``hit'' molecules from a large collection of potential drug-like candidates have relied on biophysical theory to compute approximations to the Gibbs free energy of the binding interaction between the drug to its protein target. A major drawback of the approaches is that they require exceptional computing capabilities to consider for even relatively small collections of molecules. Hyperdimensional Computing (HDC) is a recently proposed learning paradigm that is able to leverage low-precision binary vector arithmetic to build efficient representations of the data that can be obtained without the need for gradient-based optimization approaches that are required in many conventional machine learning and deep learning approaches. This algorithmic simplicity allows for acceleration in hardware that has been previously demonstrated for a range of application areas. We consider existing HDC approaches for molecular property classification and introduce two novel encoding algorithms that leverage the extended connectivity fingerprint (ECFP) algorithm. We show that HDC-based inference methods are as much as 90 times more efficient than more complex representative machine learning methods and achieve an acceleration of nearly 9 orders of magnitude as compared to inference with molecular docking. We demonstrate multiple approaches for the encoding of molecular data for HDC and examine their relative performance on a range of challenging molecular property prediction and drug-protein binding classification tasks. Our work thus motivates further investigation into molecular representation learning to develop ultra-efficient pre-screening tools

Variability in gene cassette patterns of class 1 and 2 integrons associated with multi drug resistance patterns in Staphylococcus aureus clinical isolates in Tehran-Iran

Background: To investigate antibiotic resistance, the occurrence and distribution of class 1 and 2 integrons in multidrug- resistant Staphylococcus aureus isolates from hospitals in Tehran, Iran. The isolates were examined for susceptibility to antimicrobial agents. The mecA gene, class 1 and 2 integrons were detected by PCR. Integrase positive strains were further analysed for the presence of resistance gene cassettes using specific primers and were sequenced. Results: Among 139S.aureus isolates, 109 (78.4 ) and 112 (80.5 ) strains were considered as multidrug resistant and mecA positive, respectively. Class 1 integrons and internal variable regions were found in 72.6 (101/139) and 97 (98/101) and class 2 integrons and variable regions also in 35.2 (49/139) and 65.3 (32/49) of S.aureus clinical isolates, respectively. Twelve distinct cassette arrays were found, containing genes encoding resistance to β-lactams, aminoglycosides, streptothricin, trimethoprim, chloramphenicol,a putative glucose dehydrogenase precursor and a protein with unknown function. Gene cassette arrays aadB, aadA2 and dhfrA1-sat2-aadA1 were common in S.aureus isolates. We detected a completely new gene cassettes which contained aadB, oxa2, aacA4, orfD-aacA4-catB8, aadB-catB3, orfD-aacA4 and aadB-aadA1-cmlA6 of class 1 and dhfrA1-sat2-aadA1, dhfrA11, dhfrA1-sat2 of class 2 integrons. Conclusions: This is the first study to report carriage of class 1 and 2 integrons and associated gene cassettes among in S.aureus isolates from Iran. © 2015 Mostafa et al

Erratum: Author Correction: Identification of genes required for eye development by high-throughput screening of mouse knockouts.

[This corrects the article DOI: 10.1038/s42003-018-0226-0.]

Biallelic UBE4A loss-of-function variants cause intellectual disability and global developmental delay

Purpose: To identify novel genes associated with intellectual disability (ID) in four unrelated families. Methods: Here, through exome sequencing and international collaboration, we report eight individuals from four unrelated families of diverse geographic origin with biallelic loss-of-function variants in UBE4A. Results: Eight evaluated individuals presented with syndromic intellectual disability and global developmental delay. Other clinical features included hypotonia, short stature, seizures, and behavior disorder. Characteristic features were appreciated in some individuals but not all; in some cases, features became more apparent with age. We demonstrated that UBE4A loss-of-function variants reduced RNA expression and protein levels in clinical samples. Mice generated to mimic patient-specific Ube4a loss-of-function variant exhibited muscular and neurological/behavioral abnormalities, some of which are suggestive of the clinical abnormalities seen in the affected individuals. Conclusion: These data indicate that biallelic loss-of-function variants in UBE4A cause a novel intellectual disability syndrome, suggesting that UBE4A enzyme activity is required for normal development and neurological function

Genome-wide screening reveals the genetic basis of mammalian embryonic eye development.

BACKGROUND: Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome. RESULTS: Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation. CONCLUSIONS: Using genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease

The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

Understanding the circumstances that lead to pandemics is important for their prevention. Here, we analyze the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted A and B. Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October–8 December), while the separate introduction of lineage A likely occurred within weeks of this event. These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. As with other coronaviruses, SARS-CoV-2 emergence likely resulted from multiple zoonotic events