Storylines for unprecedented heatwaves based on ensemble boosting.

Recent temperature extremes have shattered previously observed records, reaching intensities that were inconceivable before the events. Could the possibility of an event with such unprecedented intensity as the 2021 Pacific Northwest heatwave have been foreseen, based on climate model information available before the event? Could the scientific community have quantified its potential intensity based on the current generation of climate models? Here, we demonstrate how an ensemble boosting approach can be used to generate physically plausible storylines of a heatwave hotter than observed in the Pacific Northwest. We also show that heatwaves of much greater intensities than ever observed are possible in other locations like the Greater Chicago and Paris regions. In order to establish confidence in storylines of 'black swan'-type events, different lines of evidence need to be combined along with process understanding to make this information robust and actionable for stakeholders.

Heat waves in Portugal: Current regime, changes in future climate and impacts on extreme wildfires.

Heat waves (HW) can have devastating social, economic and environmental impacts. Together with long-term drought, they are the main factors contributing to wildfires. Surprisingly, the quantitative and objective analysis leading to the identification and characterization of HW in current and future climate conditions as well as its influence on the occurrence of extreme wildfires (EW) has never been performed for Portugal and are the main objectives of this study. For this reason, we assess HW in recent past and future climate based on a consistent high resolution meteorological database and have compared their occurrence with long and reliable, precise and detailed information about Portuguese fire events. Results include the characterization of HW frequency, duration, seasonality and intensity for current and different future climate conditions and their relationship with EW occurrence. We detected 130 HW between 1981 and 2010, concentrated between May and October and highest values in July and August. The highest HW number and duration is found over the Northeast corner and the south of the country while highest amplitudes are typically located in central area. HW characteristics present high inter-annual variability but are clearly associated to the temporal and spatial distribution of EW: 97% of total number of EW were active during an HW, 90% of total EW days were also HW days; 82% of the EW had duration completely contained in the duration of an HW; and, 83% of EW occurred during and in the area affected by HW. Our results also show that HW should increase in number, duration and amplitude, more significantly for RCP 8.5, and for the 30-year periods near the end of the 21st century. Findings of this study will support the definition of climate change adaptation strategies for fire danger and risk management.

Bone formation by mesenchymal progenitor cells cultured on dense and microporous hydroxyapatite particles.

Hydroxyapatite (HA) microparticles, varying in size and microporosity, were evaluated in vitro and in vivo on their suitability to be used as a carrier in an injectable tissue engineered bone filler. Depending on their manufacturing method, either dense (HA-s) or microporous (HA-r) particles were produced in diameter ranges of 212-300 microm (HA-s and HA-r) and 500-706 microm (HA-s). After seeding and culturing goat mesenchymal progenitor cells on the various particles for 1 week, sheets were produced in which multilayers of cells and extracellular matrix held the particles together. Subcutaneous implantation of the constructs in nude mice for 4 weeks revealed abundant bone formation with the 212 to 300-microm diameter particle range. Up to 30% bone was formed in the available areas between the individual microparticles, while bone marrow was present in the samples containing microporous particles. Surprisingly, no bone or bone marrow formation was apparent with the 500 to 706-microm diameter range particles. These results show that size and microporosity of HA microparticles affect the osteogenic potential of cultured cells and indicate that particles in a diameter range of 212-300 microm may be used toward the development of injectable formulations of tissue-engineered bone.

The role of complement in the acquired immune response.

Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed on B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation to specific T cells; the activation of a CD21/CD19 complex-mediated signalling pathway in B cells, which provides a stimulus synergistic to that induced by antigen interaction with the B-cell receptor (BCR); and promotion of the interaction between B cells and FDC, where C3d-bearing immune complexes participate in intercellular bridging. Finally, current studies suggest that CR2 may also play a role in the determination of B-cell tolerance towards self-antigens and thereby hold the key to the previously observed correlation between deficiencies of the early complement components and autoimmune disease.

The enhancing role of complement in human immunodeficiency virus infection: soluble recombinant CR1 (CD35) inhibits complement-mediated enhancement of infection of a CD4-positive T-cell line with human immunodeficiency virus-1.

The present study investigated the effect of soluble recombinant CR1 (srCR1, sCD35) on complement-dependent enhancement of human immunodeficiency virus-1 (HIV-1) infection in vitro. Cells of the human T-cell line HPB-ALL were infected with HIV-1 that had been preopsonized with normal human HIV-seronegative serum in the presence of srCR1. At nanomolar concentrations, srCR1 suppressed complement-dependent enhancement of infection of HPB-ALL cells in a dose-dependent manner. Under these conditions, infection was decreased to levels similar to those observed in cells infected with unopsonized virus. These observations provide further evidence to support the role of complement-dependent opsonization facilitating viral entry into target cells.

Expression of CD21 is developmentally regulated during thymic maturation of human T lymphocytes.

CD21, the C3d/CD23/Epstein-Barr virus (EBV), receptor is expressed at low density on cells of the T lineage. Immature thymocytes express CD21 with high density. In the present study, we have analyzed the expression of CD21 during intrathymic maturation of T cells. An intense staining for CD21 was observed at the double-negative stage and at the stage of early acquisition of CD4. CD21 expression was decreased at the double-positive and single-positive stages, to then reach levels similar to those of peripheral blood T cells. Staining of thymus sections showed a bright fluorescent signal on thymocytes entering the thymus in the cortical region. Taking advantage of the immature phenotype of cells expressing high amounts of CD21 (CD21(++)), we depleted thymocyte suspensions in CD3(+) and CD8(+) cells to study the properties of CD21 on this cell subset. Triggering of CD21 with its ligands iC3b, CD23 and anti-CD21 mAb did not alter the proliferative response of thymocytes to IL-7, and did not induce the differentiation of early cells into CD4(+)CD8(+) thymocytes. Immunoprecipitation did not reveal any molecule associated with CD21 that could play a signaling role in thymocytes. Finally, EBV induced a down-regulation of CD21 and an up-regulation of CD1 in CD21(++) thymocytes. Taken together, our observations demonstrate a regulated expression of CD21 on human thymocytes and suggest that the CD21(++) subset may be a target for EBV. We further suggest that CD21 on early thymocytes acts as a ligand for CD23-expressing cells in the thymus.

Functional properties of soluble CD21.

Soluble receptors may display immunoregulatory properties by blocking interactions between ligands and their membrane receptors or by triggering specific biologic responses through interaction with counter part membrane receptors. A natural soluble form of CD21 that is cleaved from lymphocyte membrane CD21 circulates in normal human serum. Soluble CD21 retains the capacity to bind iC3b and CD23, the known ligands of membrane CD21. In a similar fashion to IgE complexes, another ligand of CD23, the soluble CD21 was shown to efficiently trigger CD23-signalling pathways in human monocytes. By inducing release of proinflammatory cytokines and upregulating expression of molecules involved in antigen presentation, soluble CD21 modulates critical monocyte functions that may be relevant to allergic and inflammatory disorders.

Soluble CD21 induces activation and differentiation of human monocytes through binding to membrane CD23.

Interactions between CD23, the low-affinity receptor for IgE, and CD21, the C3d/EBV receptor, modulate several intracellular events in lymphocytes. A soluble form of CD21 (sCD21) corresponding to the extracellular domain of the receptor circulates in normal plasma. We now demonstrate that purified sCD21 acts as a functional ligand for CD23-expressing monocytes. Soluble CD21 induced an increase in intracellular cGMP levels and the production of IL-6 and TNF-alpha in IL-4-pretreated monocytes induced to express CD23 but not in unstimulated CD23- monocytes. The accumulation of cGMP and the production of TNF-alpha were inhibited by NG-monomethyl-L-arginine (L-NMMA), indicating that sCD21 activates the L-arginine pathway of NO production. We demonstrated that sCD21 activates NO synthase (NOS) since it was found to enhance the conversion of L-arginine into L-citrulline and induce the intracellular expression of inducible NOS in CD23+ monocytes. In addition, sCD21 was shown to up-regulate the expression of HLA-DR and CD40 and decrease that of CD14 on cultured CD23+ monocytes. Thus, in a fashion similar to IgE complexes, sCD21 is able to efficiently trigger CD23 signaling pathways, inducing the release of pro-inflammatory mediators by human monocytes. Soluble CD21 up-regulates the expression of molecules involved in antigen presentation, further suggesting a potential immunoregulatory function for the soluble molecule.

A sharper view of impact craters from clementine data.

The ultraviolet-visible camera on the Clementine spacecraft obtained high-spatial resolution images of the moon in five spectral channels. Impact craters mapped with these multispectral images show a scale of lithologic diversity that varies with crater size and target stratigraphy. Prominent lithologic variations (feldspathic versus basaltic) occur within the south wall of Copernicus (93 kilometers in diameter) on the scale of 1 to 2 kilometers. Lithologic diversity at Tycho (85 kilometers in diameter) is less apparent at this scale, although the impact melt of these two large craters is remarkably similar in this spectral range. The lunar surface within and around the smaller crater Giordano Bruno (22 kilometers in diameter) is largely dominated by the mixing of freshly excavated material with surrounding older soils derived from a generally similar feldspathic lithology.