Discrete element modelling of scaled railway ballast under triaxial conditions

The aim of this study is to demonstrate the use of tetrahedral clumps to model scaled railway ballast using the discrete element method (DEM). In experimental triaxial tests, the peak friction angles for scaled ballast are less sensitive to the confining pressure when compared to full-sized ballast. This is presumed to be due to the size effect on particle strength, whereby smaller particles are statistically stronger and exhibit less abrasion. To investigate this in DEM, the ballast is modelled using clumps with breakable asperities to produce the correct volumetric deformation. The effects of the quantity and properties of these asperities are investigated, and it is shown that the strength affects the macroscopic shear strength at both high and low confining pressures, while the effects of the number of asperities diminishes with increasing confining pressure due to asperity breakage. It is also shown that changing the number of asperities only affects the peak friction angle but not the ultimate friction angle by comparing the angles of repose of samples with different numbers of asperities

A high-throughput pipeline for scalable kit-free RNA extraction

An overreliance on commercial, kit-based RNA extraction in the molecular diagnoses of infectious disease presents a challenge in the event of supply chain disruptions and can potentially hinder testing capacity in times of need. In this study, we adapted a well-established, robust TRIzol-based RNA extraction protocol into a high-throughput format through miniaturization and automation. The workflow was validated by RT-qPCR assay for SARS-CoV-2 detection to illustrate its scalability without interference to downstream diagnostic sensitivity and accuracy. This semi-automated, kit-free approach offers a versatile alternative to prevailing integrated solid-phase RNA extraction proprietary systems, with the added advantage of improved cost-effectiveness for high volume acquisition of quality RNA whether for use in clinical diagnoses or for diverse molecular applications

Plasma Levels of Inter-α Inhibitor Proteins in Children with Acute Dengue Virus Infection

Background: Inter-α inhibitor proteins (IaIp) belong to a family of protease inhibitors that are involved in the haemostatic and the vascular system. Dengue viruses (DENV) infections are characterized by coagulopathy and increased vascular permeability. In this study we measured the concentration of IaIp during DENV infections and evaluated its potential as a biomarker. Methods and Findings: Concentrations of IaIp were measured in patients with acute DENV infections using a quantitative, competitive enzyme linked immunoassay. Concentrations of IaIp measured in pediatric patients suffering from severe DENV infections were significantly lower than in healthy controls. Conclusions: This is the first report to demonstrate changes in concentration of IaIp during viral infections. The data also highlight the potential of IaIp as a biological marker for severity of DENV infections

Effect of Grain Size and Shape on Undrained Behaviour of Sands

The stress–strain and stress path characteristics of sands are influenced by their grain size, shape, and packing. Morphological characteristics and size of particles play important role on the undrained shear strength of sands. Often, effects of these parameters are complex and cannot be easily distinguished. This study advances the knowledge of the role of particle size and shape on the undrained shear strength of sands. To eliminate the consequence of morphological characteristics, two sands with different particle sizes but similar angularity, and another sand with different roundness were selected for the study. These morphological characteristics for all three sands were determined from the analysis of scanning electron microscope images. F131 sand with higher median grain size and lower shape factors (rᵣ and rₛ) had highest undrained peak shear strength and phase transformation value. Undrained strength (qₚₜ) and effective principal stress (P′ₚₜ) in phase transformation point had direct relationship with grain median grain size (D₅₀) and inversely effect of shape factor (rᵣ and rₛ). F131 and F161 sands represented highest peak and ultimate steady-state strengths, respectively. Flow potential appeared to be directly proportional with (rᵣ and rₛ) and inversely with D₅₀. The peak index decreased with increasing shape factors (rᵣ and rₛ)

Emerging strengths in Asia Pacific bioinformatics

The 2008 annual conference of the Asia Pacific Bioinformatics Network (APBioNet), Asia's oldest bioinformatics organisation set up in 1998, was organized as the 7th International Conference on Bioinformatics (InCoB), jointly with the Bioinformatics and Systems Biology in Taiwan (BIT 2008) Conference, Oct. 20–23, 2008 at Taipei, Taiwan. Besides bringing together scientists from the field of bioinformatics in this region, InCoB is actively involving researchers from the area of systems biology, to facilitate greater synergy between these two groups. Marking the 10th Anniversary of APBioNet, this InCoB 2008 meeting followed on from a series of successful annual events in Bangkok (Thailand), Penang (Malaysia), Auckland (New Zealand), Busan (South Korea), New Delhi (India) and Hong Kong. Additionally, tutorials and the Workshop on Education in Bioinformatics and Computational Biology (WEBCB) immediately prior to the 20th Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) Taipei Conference provided ample opportunity for inducting mainstream biochemists and molecular biologists from the region into a greater level of awareness of the importance of bioinformatics in their craft. In this editorial, we provide a brief overview of the peer-reviewed manuscripts accepted for publication herein, grouped into thematic areas. As the regional research expertise in bioinformatics matures, the papers fall into thematic areas, illustrating the specific contributions made by APBioNet to global bioinformatics efforts

DEM of triaxial tests on crushable sand

This paper presents simulations of high-pressure triaxial shear tests on a crushable sand. The discrete element method is used, featuring a large number of particles and avoiding the use of agglomerates. The triaxial model features a flexible membrane, therefore allowing realistic deformation, and a simple breakage mechanism is implemented using the octahedral shear stress induced in the particles. The simulations show that particle crushing is essential to replicate the realistic behaviour of sand (in particular the volumetric contraction) in high-pressure shear tests. The general effects of crushing during shear are explored, including its effects on critical states, and the influence of particle strength and confining pressure on the degree of crushing are discussed

Establishing bioinformatics research in the Asia Pacific

In 1998, the Asia Pacific Bioinformatics Network (APBioNet), Asia's oldest bioinformatics organisation was set up to champion the advancement of bioinformatics in the Asia Pacific. By 2002, APBioNet was able to gain sufficient critical mass to initiate the first International Conference on Bioinformatics (InCoB) bringing together scientists working in the field of bioinformatics in the region. This year, the InCoB2006 Conference was organized as the 5(th )annual conference of the Asia-Pacific Bioinformatics Network, on Dec. 18–20, 2006 in New Delhi, India, following a series of successful events in Bangkok (Thailand), Penang (Malaysia), Auckland (New Zealand) and Busan (South Korea). This Introduction provides a brief overview of the peer-reviewed manuscripts accepted for publication in this Supplement. It exemplifies a typical snapshot of the growing research excellence in bioinformatics of the region as we embark on a trajectory of establishing a solid bioinformatics research culture in the Asia Pacific that is able to contribute fully to the global bioinformatics community

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches