All-glass shell scale models made with an adjustable mould

Ever since Lucio Blandini developed a doubly curved synclastic shell with adhesively bonded glass components, the concept of building a self-supporting glass-only shell has almost become within reach. In the current contribution a small-scaled experimental concept is presented of a self-supporting anticlastic all-glass shell scale model, created by means of an adaptable mould. First, different manufacturing parameters of relatively small shells are investigated, such as mould type, glass supporting system and dimensions, oven temperature and shell curvature. Next, an adjustable mould for the bending of glass is developed, built and tested. With this mould it is possible to make glass panels synclastic and anticlastic in a great variety of forms. With this new moulding technique we were able to create different prototypes. They are forming the basis an intended larger shell, composed of smaller segments. The objective is to join the latter by using fusing techniques, which result is completely transparent monolithic all-glass shells. Therefore, additional experiments have been performed to explore different variants of glass fusion techniques to be applied for double curved glass shells

Early Blood Cell Formation "in sickness and health, ´till death do us part"

Hematopoietic stem cells (HSC), the ancestors of all blood cells, have the ability to give rise to mature effector cells through a series of developmental steps. This is a tightly regulated, though a highly dynamic process: on the one hand, dysregulation in steady-state could lead to under- or overgrowth of certain blood cell lineages, whereas, on the other hand, demands for certain mature blood cells can change dramatically in cases like bleeding and infections. In addition to the production of differentiated offspring, HSC possess the ability to undergo self-sustaining (or self-renewing) cell divisions to ascertain life-long replenishment of the hematopoietic system. High resolution profiling of the mechanisms that guide these cellular fates does not only allow to further increase our knowledge in normal cell biology, it can also provide with clues on possible pathogenetic events in cases of altered hematopoiesis like leukemia or in the aging individual. In Article I, we have investigated the role of tumor necrosis factor (TNF) in the regulation of HSC homeostasis. We found TNF to negatively regulate HSC activity in a cell cycle dependent manner, with required signaling through both TNF receptors to elicit full inhibitory actions. Thereby, this study identifies one single, cell extrinsic factor to negatively regulate HSC activity. Blood cell production in elderly is characterized by myeloid skewing at the expense of lymphoid output, in addition to increased HSC frequencies in aged mice. However, HSC replicating activity was suggested to be decreased through increased p16INK4A signaling. To determine regulating factors underlying these observations, we assayed HSC in aged mice (Article II). We found evidence for decreased proliferative kinetics of old versus young HSC, though without proof of replicative senescence. In agreement with this, we found no evidence for increased p16INK4A signaling in aged HSC, nor for a permissive epigenetic state at the p16INK4A control region. Differentiation from a multipotent HSC to mature blood cells occurs through a series of commitment steps, generating progenitors with increasing lineage restricted potentials. The earliest lineage restricting events have been subject to debate and in Article III and IV we describe our efforts to create increased insights in the developmental steps of early myeloerythroid development. By means of flow cytometric isolation, we have identified the early granulocyte/monocyte, erythroid and megakaryocytic lineage restriction steps within the cKit+Lineage-Sca1- myeloerythroid progenitor compartment. Subsequently, functional and molecular analysis of these cellular subsets has allowed us to place these cells in a hierarchical order and understand some of the genetic events that occur during lineage specification

Contrasting surface velocities between lake- and land-terminating glaciers in the Himalayan region

This research has been supported by the Swiss National Science Foundation (grant no. IZLCZ2_169979/1) and the Strategic Priority Research Program of Chinese Academy of Sciences (grant no. XDA20100300). Bert Wouters has been supported by NWO VIDI (grant no. 016.Vidi.171.063).Meltwater from Himalayan glaciers sustains the flow of rivers such as the Ganges and Brahmaputra on which over half a billion people depend for day-to-day needs. Upstream areas are likely to be affected substantially by climate change, and changes in the magnitude and timing of meltwater supply are expected to occur in coming decades. About 10 % of the Himalayan glacier population terminates into proglacial lakes, and such lake-terminating glaciers are known to exhibit higher-than-average total mass losses. However, relatively little is known about the mechanisms driving exacerbated ice loss from lake-terminating glaciers in the Himalaya. Here we examine a composite (2017–2019) glacier surface velocity dataset, derived from Sentinel 2 imagery, covering central and eastern Himalayan glaciers larger than 3 km2. We find that centre flow line velocities of lake-terminating glaciers (N = 70; umedian: 18.83 m yr−1; IQR – interquartile range – uncertainty estimate: 18.55–19.06 m yr−1) are on average more than double those of land-terminating glaciers (N = 249; umedian: 8.24 m yr−1; IQR uncertainty estimate: 8.17–8.35 m yr−1) and show substantially more heterogeneity than land-terminating glaciers around glacier termini. We attribute this large heterogeneity to the varying influence of lakes on glacier dynamics, resulting in differential rates of dynamic thinning, which causes about half of the lake-terminating glacier population to accelerate towards the glacier termini. Numerical ice-flow model experiments show that changes in the force balance at the glacier termini are likely to play a key role in accelerating the glacier flow at the front, with variations in basal friction only being of modest importance. The expansion of current glacial lakes and the formation of new meltwater bodies will influence the dynamics of an increasing number of Himalayan glaciers in the future, and these factors should be carefully considered in regional projections.Publisher PDFPeer reviewe

Tumor necrosis factor restricts hematopoietic stem cell activity in mice: involvement of two distinct receptors.

Whereas maintenance of hematopoietic stem cells (HSCs) is a requisite for life, uncontrolled expansion of HSCs might enhance the propensity for leukemic transformation. Accordingly, HSC numbers are tightly regulated. The identification of physical cellular HSC niches has underscored the importance of extrinsic regulators of HSC homeostasis. However, whereas extrinsic positive regulators of HSCs have been identified, opposing extrinsic repressors of HSC expansion in vivo have yet to be described. Like many other acute and chronic inflammatory diseases, bone marrow (BM) failure syndromes are associated with tumor necrosis factor-α (TNF) overexpression. However, the in vivo relevance of TNF in the regulation of HSCs has remained unclear. Of considerable relevance for normal hematopoiesis and in particular BM failure syndromes, we herein demonstrate that TNF is a cell-extrinsic and potent endogenous suppressor of normal HSC activity in vivo in mice. These effects of TNF involve two distinct TNF receptors

Earth observation to investigate occurrence, characteristics and changes of glaciers, glacial lakes and rock glaciers in Poiqu River Basin (Central Himalaya)

This research has been supported by the Dragon 4 program funded by ESA (4000121469/17/I-NB), the Swiss National Science Foundation (grant nos. IZLCZ2_169979/1 and 200021E_177652/1) and the Strategic Priority Research Program of Chinese Academy of Sciences (grant no. XDA20100300).Meltwater from the cryosphere contributes a significant fraction of the freshwater resources in the countries receiving water from the Third Pole. Within the ESA-MOST Dragon 4 project, we addressed in particular changes of glaciers and proglacial lakes and their interaction. In addition, we investigated rock glaciers in permafrost environments. Here, we focus on the detailed investigations which have been performed in the Poiqu River Basin, central Himalaya. We used in particular multi-temporal stereo satellite imagery, including high-resolution 1960/70s Corona and Hexagon spy images and contemporary Pleiades data. Sentinel-2 data was applied to assess the glacier flow. The results reveal that glacier mass loss continuously increased with a mass budget of −0.42 ± 0.11 m w.e.a−1 for the period 2004–2018. The mass loss has been primarily driven by an increase in summer temperature and is further accelerated by proglacial lakes, which have become abundant. The glacial lake area more than doubled between 1964 and 2017. The termini of glaciers that flow into lakes moved on average twice as fast as glaciers terminating on land, indicating that dynamical thinning plays an important role. Rock glaciers are abundant, covering approximately 21 km2, which was more than 10% of the glacier area (approximately 190 km2) in 2015. With ongoing glacier wastage, rock glaciers can become an increasingly important water resource.Publisher PDFPeer reviewe

MLC1 is associated with the Dystrophin-Glycoprotein Complex at astrocytic endfeet

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive cerebral white matter disease with onset in childhood, caused by mutations in the MLC1 gene. MLC1 is a protein with unknown function that is mainly expressed in the brain in astrocytic endfeet at the blood–brain and cerebrospinal fluid–brain barriers. It shares its localization at astrocytic endfeet with the dystrophin-associated glycoprotein complex (DGC). The objective of the present study was to investigate the possible association of MLC1 with the DGC. To test this hypothesis, (co)-localization of DGC-proteins and MLC1 was analyzed by immunohistochemical stainings in gliotic brain tissue from a patient with multiple sclerosis, in glioblastoma tissue and in brain tissue from an MLC patient. In control tissue, a direct protein interaction was tested by immunoprecipitation. Results revealed that MLC1 is co-localized with DGC-proteins in gliotic brain tissue. We demonstrated that both MLC1 and aquaporin-4, a member of the DGC, were redistributed in glioblastoma cells. In MLC brain tissue, we showed absence of MLC1 and altered expression of several DGC-proteins. We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet

Spong3d: 3D printed facade system enabling movable fluid heat storage

Spong3D is an adaptive 3D printed facade system that integrates multiple functions to optimize thermal performances according to the different environmental conditions throughout the year. The proposed system incorporates air cavities to provide thermal insulation and a movable liquid (water plus additives) to provide heat storage where and whenever needed. The air cavities have various dimensions and are located in the inner part of the system. The movable liquid provides heat storage as it flows through channels located along the outer surfaces of the system (on the indoor and outdoor faces of the façade). Together, the composition of the channels and the cavities form a complex structure, integrating multiple functions into a singular component, which can only be produced by using an Additive Manufacturing (AM; like 3D printing) technology

Spong3d: 3D printed facade system enabling movable fluid heat storage

Spong3D is an adaptive 3D printed facade system that integrates multiple functions to optimize thermal performances according to the different environmental conditions throughout the year. The proposed system incorporates air cavities to provide thermal insulation and a movable liquid (water plus additives) to provide heat storage where and whenever needed. The air cavities have various dimensions and are located in the inner part of the system. The movable liquid provides heat storage as it flows through channels located along the outer surfaces of the system (on the indoor and outdoor faces of the façade). Together, the composition of the channels and the cavities form a complex structure, integrating multiple functions into a singular component, which can only be produced by using an Additive Manufacturing (AM; like 3D printing) technology

Chemotherapy and Tyrosine Kinase Inhibitors in the last month of life in patients with metastatic lung cancer: A patient file study in the Netherlands

Objective: Chemotherapy in the last month of life for patients with metastatic lung cancer is often considered as aggressive end-of-life care. Targeted therapy with Tyrosine Kinase Inhibitors (TKIs) is a relatively new treatment of which not much is known yet about use in the last month of life. We examined what percentage of patients received chemotherapy or TKIs in the last month of life in the Netherlands. Methods: Patient files were drawn from 10 hospitals across the Netherlands. Patients had to meet the following eligibility criteria: metastatic lung cancer; died between June 1, 2013 and July 31, 2015. Results: From the included 1,322 patients, 39% received no treatment for metastatic lung cancer, 52% received chemotherapy and 9% received TKIs. A total of 232 patients (18%) received treatment in the last month of life (11% chemotherapy, 7% TKIs). From the patients who received chemotherapy, 145 (21%) received this in the last month of life and 79 (11%) started this treatment in the last month of life. TKIs were given and started more often in the last month of life: from the patients who received TKIs, 87 (72%) received this treatment in the last month of life and 15 (12%) started