Targeting CD20-expressing malignant melanoma cells augments BRAF inhibitor killing.

Background: Mutant BRAF targeted therapies remain a standard of care for the treatment of metastatic malignant melanoma (MM); however, high initial response rates are tempered by the persistence of residual MM cells that eventually lead to disease recurrence and mortality. As MM recurrence during targeted therapy can present with the simultaneous occurrence of multiple tumour nodules at the original body sites, we hypothesized the presence of an intrinsically resistant MM cell subpopulation.

Objectives: To identify an MM cell subpopulation that is intrinsically resistant to targeted therapy and possibly responsible for MM recurrence.

CAR T cells and time-limited ibrutinib as treatment for relapsed/refractory mantle cell lymphoma: the phase 2 TARMAC study.

CD19-directed chimeric antigen receptor T cells (CAR-T) achieve high response rates in patients with relapsed/refractory mantle cell lymphoma (MCL). However, their use is associated with significant toxicity, relapse concern, and unclear broad tractability. Preclinical and clinical data support a beneficial synergistic effect of ibrutinib on apheresis product fitness, CAR-T expansion, and toxicity.

Spatial proteomics identifies a spectrum of immune dysregulation in acquired bone marrow failure syndromes.

Poor graft function (PGF), manifested by multilineage cytopenias and complete donor chimerism post-allogeneic stem cell transplantation (alloSCT), and acquired aplastic anaemia (AA) are immune-mediated acquired bone marrow (BM) failure syndromes with a similar clinical presentation. In this study, we used spatial proteomics to compare the immunobiology of the BM microenvironment and identify common mechanisms of immune dysregulation under these conditions. Archival BM trephines from patients exhibited downregulation of the immunoregulatory protein VISTA and the M2 macrophage marker and suppressor of T-cell activation ARG1 with increased expression of the immune checkpoint B7-H3 compared to normal controls.

CD200 ectodomain shedding into the tumor microenvironment leads to NK cell dysfunction and apoptosis.

The basis of immune evasion, a hallmark of cancer, can differ even when cancers arise from one cell type such as in the human skin keratinocyte carcinomas: basal and squamous cell carcinoma. Here we showed that the basal cell carcinoma tumor-initiating cell surface protein CD200, through ectodomain shedding, was responsible for the near absence of NK cells within the basal cell carcinoma tumor microenvironment. In situ, CD200 underwent ectodomain shedding by metalloproteinases MMP3 and MMP11, which released biologically active soluble CD200 into the basal cell carcinoma microenvironment.

Regulation of dendritic cell function by Fc-γ-receptors and the neonatal Fc receptor.

Dendritic cells (DCs) express receptors to sense pathogens and/or tissue damage and to communicate with other immune cells. Among those receptors, Fc receptors (FcRs) are triggered by the Fc region of antibodies produced during adaptive immunity. In this review, the role of FcγR and neonatal Fc receptor (FcRn) in DC immunity will be discussed.

Within-day variability in microbial concentrations at a UK designated bathing water: Implications for regulatory monitoring and the application of predictive modelling based on historical compliance data.

Prediction of bathing water quality is recommended by the World Health Organization (WHO), the European Union (EU) and the United States Environmental Protection Agency (USEPA) and is an established element in bathing water management designed to protect public health. Most commonly, historical regulatory compliance data are used for model calibration and provide the dependent variable for modelling. Independent (or predictor) variables (e.

Global Non-Potential Magnetic Models of the Solar Corona During the March 2015 Eclipse.

Seven different models are applied to the same problem of simulating the Sun's coronal magnetic field during the solar eclipse on 2015 March 20. All of the models are non-potential, allowing for free magnetic energy, but the associated electric currents are developed in significantly different ways. This is not a direct comparison of the coronal modelling techniques, in that the different models also use different photospheric boundary conditions, reflecting the range of approaches currently used in the community.

Identification of Human Cutaneous Basal Cell Carcinoma Cancer Stem Cells.

The cancer stem cell model states that a subset of tumor cells, called "cancer stem cells," can initiate and propagate tumor growth through self-renewal, high proliferative capacity, and their ability to recreate tumor heterogeneity. In basal cell carcinoma (BCC), we have shown that tumor cells that express the cell surface protein CD200 fulfill the cancer stem cell hypothesis. CD200+ CD45- BCC cells represent 0.

Identification of Human Cutaneous Squamous Cell Carcinoma Cancer Stem Cells.

Epithelia are under constant threat from environmental carcinogens and none more so than squamous epithelia, which form the outermost linings of our bodies. Hence malignancies of squamous epithelia are collectively the most common cancer type and with the highest mortality, despite a constant cell turnover and only relatively rare long-lived adult tissue stem cells. Genetic analysis from SCC whole genome sequencing reveals commonality in mutated genes, despite various etiological factors.

Global conditions in the solar corona from 2010 to 2017.

Through reduction of a huge data set spanning 2010-2017, we compare mean global changes in temperature, emission measure (EM), and underlying photospheric magnetic field of the solar corona over most of the last activity cycle. The quiet coronal mean temperature rises from 1.4 to 1.

Multi-Scale Gaussian Normalization for Solar Image Processing.

Unlabelled: Extreme ultra-violet images of the corona contain information over a wide range of spatial scales, and different structures such as active regions, quiet Sun, and filament channels contain information at very different brightness regimes. Processing of these images is important to reveal information, often hidden within the data, without introducing artefacts or bias. It is also important that any process be computationally efficient, particularly given the fine spatial and temporal resolution of on the (AIA/SDO), and consideration of future higher resolution observations.

Gene and protein responses of human lung tissue explants exposed to ambient particulate matter of different sizes.

Context: Exposure to ambient particulate air pollution is associated with increased cardiovascular and respiratory morbidity and mortality. It is necessary to understand causal pathways driving the observed health effects, particularly if they are differentially associated with particle size.

Objectives: To investigate the effect of different size ranges of ambient particulate matter (PM) on gene and protein expression in an in vitro model.

Medical humanities in Nepal--snakes and ladders.

In the last decade there has been a quantitative growth in medical schools in Nepal, a developing country in South Asia. Medical Humanities (MH) uses disciplines traditionally termed as the humanities in the pursuit of medical educational goals. The subject is slowly developing in Nepal.

The relationship between nuclear DNA content and leaf strategy in seed plants.

Background And Aims: Species' 2C-values (mass of DNA in G(1) phase 2n nuclei) vary by at least four orders of magnitude among seed plants. The 2C-value has been shown to be co-ordinated with a number of other species traits, and with environmental variables. A prediction that species 2C-values are negatively related to leaf life span (LL) and leaf mass per area (LMA) is tested.

Effectiveness of aeration and mixing in the remediation of a saline stratified river.

This study examines the use of an aeration scheme to remediate low oxygen conditions in a saline stratified system. The Tawe estuary was impounded in 1992 and quickly developed saline stratification during the summer months which led to an anoxic hypolimnon. In 1998 trials began in which a suite of aerators was applied to remediate the water quality; the trial was later extended to a full aeration scheme.