Brandon’s Matrix:A view on scientific methods in biology classrooms

Many biology textbooks open with a section on the scientific method, and usually laboratory activities involve a stepwise procedure that is followed in a formulaic fashion Although there are many accounts of the scientific method in biology, they are often problematic as they are not comprehensive in showing the diversity of scientific methods. To solve some tensions regarding the definition of the scientific methods in biology, we introduce Brandon’s Matrix as a framework that helps show the complexity of methods as a simple two-by-two matrix. It represents the connections between experiments and observations. Brandon illustrates not all experiments rely on hypothesis testing and not all descriptive work is non-manipulative, as they rely more on a diversity of approaches including parameter measurements. According to Brandon, the nature of the investigation is related to whether or not it involves (i) manipulation and (ii) hypothesis testing or a parameter measurement. In this way, one can think in terms of experiments and non-experiments/observations relative to descriptive versus experimental methods. Hence, Brandon’s framework goes beyond the traditional limitations of the scientific method as a linear process of hypothesis testing and provides a more comprehensive, inclusive and realistic account of methods applied by biologists, for both current and historical studies. The chapter will introduce the framework and show its use in a research project with schools in England to produce resources, as well as its utility as an analytical framework for curriculum and assessment documents

Complete Supersymmetric Quantum Mechanics of Magnetic Monopoles in N=4 SYM Theory

We find the most general low energy dynamics of 1/2 BPS monopoles in the N=4 supersymmetric Yang-Mills theories (SYM) when all six adjoint Higgs expectation values are turned on. When only one Higgs is turned on, the Lagrangian is purely kinetic. When all six are turned on, however, this moduli space dynamics is augmented by five independent potential terms, each in the form of half the squared norm of a Killing vector field on the moduli space. A generic stationary configuration of the monopoles can be interpreted as stable non BPS dyons, previously found as non-planar string webs connecting D3-branes. The supersymmetric extension is also found explicitly, and gives the complete quantum mechanics of monopoles in N=4 SYM theory. We explore its supersymmetry algebra.Comment: Errors in the SUSY algebra corrected. The version to appear in PR

Low Avidity T Cells Do Not Hinder High Avidity T Cell Responses Against Melanoma

The efficacy of T cells depends on their functional avidity, i. e., the strength of T cell interaction with cells presenting cognate antigen. The overall T cell response is composed of multiple T cell clonotypes, involving different T cell receptors and variable levels of functional avidity. Recently, it has been proposed that the presence of low avidity tumor antigen-specific CD8 T cells hinder their high avidity counterparts to protect from tumor growth. Here we analyzed human cytotoxic CD8 T cells specific for the melanoma antigen Melan-A/MART-1. We found that the presence of low avidity T cells did not result in reduced cytotoxicity of tumor cells, nor reduced cytokine production, by high avidity T cells. In vivo in NSG-HLA-A2 mice, the anti-tumor effect of high avidity T cells was similar in presence or absence of low avidity T cells. These data indicate that low avidity T cells are not hindering anti-tumor T cell responses, a finding that is reassuring because low avidity T cells are an integrated part of natural T cell responses

Comments on Noncommutative Sigma Models

We review the derivation of a noncommutative version of the nonlinear sigma model on \CPn and it's soliton solutions for finite $\theta$ emphasizing the similarities it bears to the GMS scalar field theory. It is also shown that unlike the scalar theory, some care needs to be taken in defining the topological charge of BPS solitons of the theory due to nonvanishing surface terms in the energy functional. Finally it is shown that, like its commutative analogue, the noncommutative \CPn-model also exhibits a non-BPS sector. Unlike the commutative case however, there are some surprises in the noncommutative case that merit further study.Comment: 22 pages, 4 figures, LaTeX (JHEP3), Minor changes, Discussion expanded and references adde

Mutually exclusive lymphangiogenesis or perineural infiltration in human skin squamous-cell carcinoma.

Although tumor-associated lymphangiogenesis correlates with metastasis and poor prognosis in several cancers, it also supports T cell infiltration into the tumor and predicts favorable outcome to immunotherapy. The role of lymphatic vessels in skin squamous-cell carcinoma (sSCC), the second most common form of skin cancer, remains mostly unknown. Although anti-PD-1 therapy is beneficial for some patients with advanced sSCC, a greater understanding of disease mechanisms is still needed to develop better therapies. Using quantitative multiplex immunohistochemistry, we analyzed sSCC sections from 36 patients. CD8+ T cell infiltration showed great differences between patients, whereby these cells were mainly excluded from the tumor mass. Similar to our data in melanoma, sSCC with high density of lymphatic endothelial cells showed increased CD8+ T cell density in tumor areas. An entirely new observation is that sSCC with perineural infiltration but without metastasis was characterized by low lymphatic endothelial cell density. Since both, metastasis and perineural infiltration are known to affect tumor progression and patients' prognosis, it is important to identify the molecular drivers, opening future options for therapeutic targeting. Our data suggest that the mechanisms underlying perineural infiltration may be linked with the biology of lymphatic vessels and thus stroma

Non-BPS Dyons and Branes in the Dirac-Born-Infeld Theory

Non-BPS dyon solutions to D3-brane actions are constructed when one or more scalar fields describing transverse fluctuations of the brane, are considered. The picture emerging from such non-BPS configurations is analysed, in particular the response of the D-brane-string system to small perturbations.Comment: 16 pages, 4 figures, Revtex fil

Dispersionless limit of the noncommutative potential KP hierarchy and solutions of the pseudodual chiral model in 2+1 dimensions

The usual dispersionless limit of the KP hierarchy does not work in the case where the dependent variable has values in a noncommutative (e.g. matrix) algebra. Passing over to the potential KP hierarchy, there is a corresponding scaling limit in the noncommutative case, which turns out to be the hierarchy of a `pseudodual chiral model' in 2+1 dimensions (`pseudodual' to a hierarchy extending Ward's (modified) integrable chiral model). Applying the scaling procedure to a method generating exact solutions of a matrix (potential) KP hierarchy from solutions of a matrix linear heat hierarchy, leads to a corresponding method that generates exact solutions of the matrix dispersionless potential KP hierarchy, i.e. the pseudodual chiral model hierarchy. We use this result to construct classes of exact solutions of the su(m) pseudodual chiral model in 2+1 dimensions, including various multiple lump configurations.Comment: 37 pages, 10 figures, 2nd version: some extensions (Fig 3, Appendix A, additional references), 3rd version: some minor changes, additional reference

Where two worlds meet: language policing in mainstream and complementary schools in England

We compare language policing in two educational contexts in England: mainstream schools and complementary schools. We draw on a varied dataset (policy documents, in-class observations, interviews) collected from mainstream schools and Greek complementary schools in London. We find similarities in how the two types of schools control, regulate, monitor and suppress the language of school students. Both settings hierarchise standardised and non-standardised varieties in institutional policies that delegitimise the non-standardised varieties. Teachers become vehicles for language ideologies in enacting monovarietal policies drawing on discourses around academic success and the primacy of written language over spoken language, including regional varieties such as Cypriot Greek. Our findings suggest that multilingual and multidialectal students in England who attend both mainstream and complementary schools are exposed to similar kinds of prescriptive discourses across the whole spectrum of their educational experiences, which can have a range of negative effects on their learning and the construction of their self-image. We argue that more links need to be forged between the two educational settings and that these should include the development of integrated pedagogies and policies that legitimise students’ whole linguistic repertoires, encompassing both their standardised and their non-standardised varieties as well as their other linguistic resources

Lymphatic vessel density is associated with CD8⁺ T cell infiltration and immunosuppressive factors in human melanoma.

Increased density of tumor-associated lymphatic vessels correlates with poor patient survival in melanoma and other cancers, yet lymphatic drainage is essential for initiating an immune response. Here we asked whether and how lymphatic vessel density (LVD) correlates with immune cell infiltration in primary tumors and lymph nodes (LNs) from patients with cutaneous melanoma. Using immunohistochemistry and quantitative image analysis, we found significant positive correlations between LVD and CD8 <sup>+</sup> T cell infiltration as well as expression of the immunosuppressive molecules inducible nitric oxide synthase (iNOS) and 2,3-dioxygénase (IDO). Interestingly, similar associations were seen in tumor-free LNs adjacent to metastatic ones, indicating loco-regional effects of tumors. Our data suggest that lymphatic vessels play multiple roles at tumor sites and LNs, promoting both T cell infiltration and adaptive immunosuppressive mechanisms. Lymph vessel associated T cell infiltration may increase immunotherapy success rates provided that the treatment overcomes adaptive immune resistance

Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement.

T-follicular helper (Tfh) cells, co-expressing PD-1 and TIGIT, serve as a major cell reservoir for HIV-1 and are responsible for active and persistent HIV-1 transcription after prolonged antiretroviral therapy (ART). However, the precise mechanisms regulating HIV-1 transcription in lymph nodes (LNs) remain unclear. In the present study, we investigated the potential role of immune checkpoint (IC)/IC-Ligand (IC-L) interactions on HIV-1 transcription in LN-microenvironment. We show that PD-L1 (PD-1-ligand) and CD155 (TIGIT-ligand) are predominantly co-expressed on LN migratory (CD1chighCCR7+CD127+) dendritic cells (DCs), that locate predominantly in extra-follicular areas in ART treated individuals. We demonstrate that TCR-mediated HIV production is suppressed in vitro in the presence of recombinant PD-L1 or CD155 and, more importantly, when LN migratory DCs are co-cultured with PD-1+/Tfh cells. These results indicate that LN migratory DCs expressing IC-Ls may more efficiently restrict HIV-1 transcription in the extra-follicular areas and explain the persistence of HIV transcription in PD-1+/Tfh cells after prolonged ART within germinal centers