Three-Dimensional Cyclic Behaviour of Interfaces

A new apparatus is used to study the behavior of an interface between dry sand and a rough surface under three dimensional cyclic loading conditions. A simple shear type of soil container is utilized in the experiments to investigate the coupling effects of two orthogonal shear stresses acting on the interface. The significance of the results are discussed with reference to the behavior of axially-laterally loaded piles

Complex Networks on a Rock Joint

A complex network approach on a rough fracture is developed. In this manner, some hidden metric spaces (similarity measurements) between apertures profiles are set up and a general evolutionary network in two directions (in parallel and perpendicular to the shear direction) is constructed. Also, an algorithm (COmplex Networks on Apertures: CONA) is proposed in which evolving of a network is accomplished using preferential detachments and attachments of edges (based on a competition and game manner) while the number of nodes is fixed. Also, evolving of clustering coefficients and number of edges display similar patterns as well as are appeared in shear stress, hydraulic conductivity and dilation changes, which can be engaged to estimate shear strength distribution of asperities.Comment: ROCKENG09: Proceedings of the 3rd CANUS Rock Mechanics Symposium, Toronto, May 2009 (Ed: M.Diederichs and G. Grasselli

Simple Shear Versus Direct Shear Tests on Interfaces during Cyclic Loading

An apparatus capable of direct shear type and simple shear type testing of interfaces between soil and structural materials is developed. A series of monotonic and cyclic tests are conducted at the interfaces between dry sand and a rough surface under constant normal stress conditions with both methods. The test results indicate that the peak and residual shear strengths obtained from direct shear and simple shear are approximately the same. However, the simple shear box permits separate measurements of shear deformation of the sand mass and also sliding at the contact surface

Lessons for the Next Generation of Scientists from the Second Annual Arthur and Sandra Irving Cancer Immunology Symposium

The Arthur and Sandra Irving Cancer Immunology Symposium has been created as a platform for established cancer immunologists to mentor trainees and young investigators as they launch their research career in the field. By sharing their different paths to success, the senior faculty mentors provide an invaluable resource to support the development of the next generation of leaders in the cancer immunology community. This Commentary describes some of the key topics that were discussed during the 2022 symposium: scientific and career trajectory, leadership, mentoring, collaborations, and publishing. For each of these topics, established investigators discussed the elements that facilitate success in these areas as well as mistakes that can hinder progress. Herein, we outline the critical points raised in these discussions for establishing a successful independent research career. These points are highly relevant for the broader scientific community

Subversion of NK-cell and TNFα Immune Surveillance Drives Tumor Recurrence

Understanding how incompletely cleared primary tumors transition from minimal residual disease (MRD) into treatment resistant, immune-invisible recurrences has major clinical significance. We show here that this transition is mediated through the subversion of two key elements of innate immune surveillance. In the first, the role of TNFalpha changes from an antitumor effector against primary tumors into a growth promoter for MRD. Second, whereas primary tumors induced a natural killer (NK)-mediated cytokine response characterized by low IL6 and elevated IFNgamma, PD-L1hi MRD cells promoted the secretion of IL6 but minimal IFNgamma, inhibiting both NK cell and T-cell surveillance. Tumor recurrence was promoted by trauma- or infection-like stimuli inducing VEGF and TNFalpha which stimulated the growth of MRD tumors. Finally, therapies which blocked PD1, TNFalpha or NK cells delayed or prevented recurrence. These data show how innate immune surveillance mechanisms, which control infection and growth of primary tumors, are exploited by recurrent, competent tumors and identifies therapeutic targets in patients with MRD known to be at high risk of relapse

Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy

In our clinical trials of oncolytic vesicular stomatitis virus expressing interferon beta (VSV-IFNβ), several patients achieved initial responses followed by aggressive relapse. We show here that VSV-IFNβ-escape tumors predictably express a point-mutated CSDE1P5S form of the RNA-binding Cold Shock Domain-containing E1 protein, which promotes escape as an inhibitor of VSV replication by disrupting viral transcription. Given time, VSV-IFNβ evolves a compensatory mutation in the P/M Inter-Genic Region which rescues replication in CSDE1P5S cells. These data show that CSDE1 is a major cellular co-factor for VSV replication. However, CSDE1P5S also generates a neo-epitope recognized by non-tolerized T cells. We exploit this predictable neo-antigenesis to drive, and trap, tumors into an escape phenotype, which can be ambushed by vaccination against CSDE1P5S, preventing tumor escape. Combining frontline therapy with escape-targeting immunotherapy will be applicable across multiple therapies which drive tumor mutation/evolution and simultaneously generate novel, targetable immunopeptidomes associated with acquired treatment resistance

A Selectable and Excisable Marker System for the Rapid Creation of Recombinant Poxviruses

Genetic manipulation of poxvirus genomes through attenuation, or insertion of therapeutic genes has led to a number of vector candidates for the treatment of a variety of human diseases. The development of recombinant poxviruses often involves the genomic insertion of a selectable marker for purification and selection purposes. The use of marker genes however inevitably results in a vector that contains unwanted genetic information of no therapeutic value.Here we describe an improved strategy that allows for the creation of marker-free recombinant poxviruses of any species. The Selectable and Excisable Marker (SEM) system incorporates a unique fusion marker gene for the efficient selection of poxvirus recombinants and the Cre/loxP system to facilitate the subsequent removal of the marker. We have defined and characterized this new methodological tool by insertion of a foreign gene into vaccinia virus, with the subsequent removal of the selectable marker. We then analyzed the importance of loxP orientation during Cre recombination, and show that the SEM system can be used to introduce site-specific deletions or inversions into the viral genome. Finally, we demonstrate that the SEM strategy is amenable to other poxviruses, as demonstrated here with the creation of an ectromelia virus recombinant lacking the EVM002 gene.The system described here thus provides a faster, simpler and more efficient means to create clinic-ready recombinant poxviruses for therapeutic gene therapy applications

Analysis of Complex Gamma Spectra

A general method of analysis for complex gamma spectra has been used to analyse the experimental data obtained with a dual gamma-ray scanner. The measured mass attenuation coefficients of water for americium and cesium isotopes were within 1 per cent of the theoretical values. In addition, the application of the method resulted in the development of a relationship between the cesium readings and the influence of cesium on the count rates of americium. The relationship can be used to correct americium readings and it will significantly reduce the amount of data to be recorded and the time spent for analysis.On a utilis\ue9 une m\ue9thode g\ue9n\ue9rale d'analyse des spectres gamma complexes pour \ue9tudier les donn\ue9es exp\ue9rimentales obtenues avec un explorateur \ue0 rayons gamma double. Les coefficients d'att\ue9nuation massique de l'eau mesur\ue9s pour les isotopes de l'am\ue9ricium et du c\ue9sium ne s'\ue9cartaient pas des ivaleurs th\ue9oriques par plus de 1pour cent. De plus, la m\ue9thode a permis d'\ue9tablir une relation entre les lectures concernant le c\ue9sium et de d\ue9terminer l'influence du c\ue9sium sur les taux de comptage de l'am\ue9ricium. La relation peut \ueatre utilis\ue9e pour corriger les lectures concernant l'am\ue9ricium et permettra de r\ue9duire de fa\ue7on appr\ue9ciable la quantit\ue9 de donn\ue9es \ue0 recueillir et le temps consacr\ue9 \ue0 l'analyse.Peer reviewed: NoNRC publication: Ye