EMI protection design guidance

This EMI Protection Design Guidelines report has been prepared as a guide for use by ALSEP experiment fabrication and subsystem designers.prepared by J. Whiteford, R. L. Lewis

The CMV early enhancer/chicken β actin (CAG) promoter can be used to drive transgene expression during the differentiation of murine embryonic stem cells into vascular progenitors

<p>Abstract</p> <p>Background</p> <p>Mouse embryonic stem cells cultured <it>in vitro </it>have the ability to differentiate into cells of the three germ layers as well as germ cells. The differentiation mimics early developmental events, including vasculogenesis and early angiogenesis and several differentiation systems are being used to identify factors that are important during the formation of the vascular system. Embryonic stem cells are difficult to transfect, while downregulation of promoter activity upon selection of stable transfectants has been reported, rendering the study of proteins by overexpression difficult.</p> <p>Results</p> <p>CCE mouse embryonic stem cells were differentiated on collagen type IV for 4–5 days, Flk1⁺mesodermal cells were sorted and replated either on collagen type IV in the presence of VEGFA to give rise to endothelial cells and smooth muscle cells or in collagen type I gels for the formation of vascular tubes. The activity of the CMV and β-actin promoters was downregulated during selection of stable transfectants and during differentiation to the Flk1 stage, while the CMV immediate enhancer/β-actin promoter in the pCAGIPuro-GFP vector led to 100% of stably transfected undifferentiated and differentiated cells expressing GFP. To further test this system we expressed syndecan-2 and -4 in these cells and demonstrated high levels of transgene expression in both undifferentiated cells and cells differentiated to the Flk1 stage.</p> <p>Conclusion</p> <p>Vectors containing the CAG promoter offer a valuable tool for the long term expression of transgenes during stem cell differentiation towards mesoderm, while the CMV and β-actin promoters lead to very poor transgene expression during this process.</p

Spatial patterns of climate change across the Paleocene–Eocene Thermal Maximum

This study was supported by Heising–Simons Founda-tion Grants 2016-015 (to J.E.T.), 2016-011 (to M.L. and L.R.K.), 2016-013 (toA.R.), 2016-014 (to G.J.H.), and 2016-012 (to C.J.P.). R.D.M.W. and J.W.B.R. acknowledge funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program Grant 805246. This material is based on work supported by the National Center for Atmospheric Research (NCAR), which is a major facility sponsored by NSF Cooperative Agreement 1852977. Computing and data storage resources, including the Cheyenne supercomputer (https://arc.ucar.edu/knowledgebase/70549542), were provided by the Computational and Information Systems Laboratory at NCAR.The Paleocene–Eocene Thermal Maximum (PETM; 56 Ma) is one of our best geological analogs for understanding climate dynamics in a “greenhouse” world. However, proxy data representing the event are only available from select marine and terrestrial sedimentary sequences that are unevenly distributed across Earth’s surface, limiting our view of the spatial patterns of climate change. Here, we use paleoclimate data assimilation (DA) to combine climate model and proxy information and create a spatially complete reconstruction of the PETM and the climate state that precedes it (“PETM-DA”). Our data-constrained results support strong polar amplification, which in the absence of an extensive cryosphere, is related to temperature feedbacks and loss of seasonal snow on land. The response of the hydrological cycle to PETM warming consists of a narrowing of the Intertropical Convergence Zone, off-equatorial drying, and an intensification of seasonal monsoons and winter storm tracks. Many of these features are also seen in simulations of future climate change under increasing anthropogenic emissions. Since the PETM-DA yields a spatially complete estimate of surface air temperature, it yields a rigorous estimate of global mean temperature change (5.6 ∘C; 5.4 ∘C to 5.9 ∘C, 95% CI) that can be used to calculate equilibrium climate sensitivity (ECS). We find that PETM ECS was 6.5 ∘C (5.7 ∘C to 7.4 ∘C, 95% CI), which is much higher than the present-day range. This supports the view that climate sensitivity increases substantially when greenhouse gas concentrations are high.Publisher PDFPeer reviewe

Pathological Angiogenesis Requires Syndecan-4 for Efficient VEGFA-Induced VE-Cadherin Internalization

Objective: VEGFA (Vascular endothelial growth factor A) and its receptor VEGFR2 (vascular endothelial growth factor receptor 2) drive angiogenesis in several pathologies, including diabetic retinopathy, wet age-related macular degeneration, and cancer. Studies suggest roles for HSPGs (heparan sulfate proteoglycans) in this process, although the nature of this involvement remains elusive. Here, we set to establish the role of the HSPG SDC4 (syndecan-4) in pathological angiogenesis. Approach and Results: We report that angiogenesis is impaired in mice null for SDC4 in models of neovascular eye disease and tumor development. Our work demonstrates that SDC4 is the only SDC whose gene expression is upregulated during pathological angiogenesis and is selectively enriched on immature vessels in retinas from diabetic retinopathy patients. Combining in vivo and tissue culture models, we identified SDC4 as a downstream mediator of functional angiogenic responses to VEGFA. We found that SDC4 resides at endothelial cell junctions, interacts with vascular endothelial cadherin, and is required for its internalization in response to VEGFA. Finally, we show that pathological angiogenic responses are inhibited in a model of wet age-related macular degeneration by targeting SDC4. Conclusions: We show that SDC4 is a downstream mediator of VEGFA-induced vascular endothelial cadherin internalization during pathological angiogenesis and a potential target for antiangiogenic therapies.acceptedVersionPeer reviewe

Methane Emission From a Cool Brown Dwarf

© 2024, The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Beyond our solar system, aurorae have been inferred from radio obser- vations of isolated brown dwarfs (e.g. [1]; [2]). Within our solar system, giant planets have auroral emission with signatures across the electromag- netic spectrum including infrared emission of H3+ and methane. Isolated brown dwarfs with auroral signatures in the radio have been searched for corresponding infrared features but have only had null detections (e.g. [3]). CWISEP J193518.59-154620.3. (W1935 for short) is an isolated brown dwarf with a temperature of ∼482 K. Here we report JWST observations of strong methane emission from W1935 at 3.326 microns. Atmospheric mod- eling leads us to conclude that a temperature inversion of ∼300 K centered at 1-10 millibar replicates the feature. This represents an atmospheric tem- perature inversion for a Jupiter-like atmosphere without irradiation from a host star. A plausible explanation for the strong inversion is heating by auroral processes, although other internal and/or external dynamical pro- cesses cannot be ruled out. The best fit model rules out the contribution of H3+ emission which is prominent in solar system gas giants, however this is consistent with rapid destruction of H3+ at the higher pressure where the W1935 emission originates (e.g. [4]).Peer reviewe

ICAM-1-expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia

This work was supported by funds from the Wellcome Trust (098291/Z/12/Z and 101604/Z/13/Z) (S.N.) and the British Heart Foundation (FS/11/19/28761) (A.W.)

ROR2 blockade as a therapy for osteoarthritis

Osteoarthritis is characterized by the loss of the articular cartilage, bone remodeling, pain, and disability. No pharmacological intervention can currently halt progression of osteoarthritis. Here, we show that blocking receptor tyrosine kinase–like orphan receptor 2 (ROR2) improves cartilage integrity and pain in osteoarthritis models by inhibiting yes-associated protein (YAP) signaling. ROR2 was up-regulated in the cartilage in response to inflammatory cytokines and mechanical stress. The main ligand for ROR2, WNT5A, and the targets YAP and connective tissue growth factor were up-regulated in osteoarthritis in humans. In vitro, ROR2 overexpression inhibited chondrocytic differentiation. Conversely, ROR2 blockade triggered chondrogenic differentiation of C3H10T1/2 cells and suppressed the expression of the cartilage-degrading enzymes a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)–4 and ADAMTS-5. The chondrogenic effect of ROR2 blockade in the cartilage was independent of WNT signaling and was mediated by down-regulation of YAP signaling. ROR2 signaling induced G protein and Rho-dependent nuclear accumulation of YAP, and YAP inhibition was required but not sufficient for ROR2 blockade–induced chondrogenesis. ROR2 silencing protected mice from instability-induced osteoarthritis with improved structural outcomes, sustained pain relief, and without apparent side effects or organ toxicity. Last, ROR2 silencing in human articular chondrocytes transplanted in nude mice led to the formation of cartilage organoids with more and better differentiated extracellular matrix, suggesting that the anabolic effect of ROR2 blockade is conserved in humans. Thus, ROR2 blockade is efficacious and well tolerated in preclinical animal models of osteoarthritis