Porous polymer networks (PPNs) are a class of advanced porous materials that combine the advantages of cheap and stable polymers with the high surface areas and tunable chemistry of metal–organic ...frameworks. They are of particular interest for gas separation or storage applications, for instance, as methane adsorbents for a vehicular natural gas tank or other portable applications. PPNs are self-assembled from distinct building units; here, we utilize commercially available chemical fragments and two experimentally known synthetic routes to design in silico a large database of synthetically realistic PPN materials. All structures from our database of 18,000 materials have been relaxed with semiempirical electronic structure methods and characterized with Grand-canonical Monte Carlo simulations for methane uptake and deliverable (working) capacity. A number of novel structure–property relationships that govern methane storage performance were identified. The relationships are translated into experimental guidelines to realize the ideal PPN structure. We found that cooperative methane–methane attractions were present in all of the best-performing materials, highlighting the importance of guest interaction in the design of optimal materials for methane storage.
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IJS, KILJ, NUK, PNG, UL, UM
Heterogeneity between different macrophage populations has become a defining feature of this lineage. However, the conserved factors defining macrophages remain largely unknown. The transcription ...factor ZEB2 is best described for its role in epithelial to mesenchymal transition; however, its role within the immune system is only now being elucidated. We show here that Zeb2 expression is a conserved feature of macrophages. Using Clec4f-cre, Itgax-cre, and Fcgr1-cre mice to target five different macrophage populations, we found that loss of ZEB2 resulted in macrophage disappearance from the tissues, coupled with their subsequent replenishment from bone-marrow precursors in open niches. Mechanistically, we found that ZEB2 functioned to maintain the tissue-specific identities of macrophages. In Kupffer cells, ZEB2 achieved this by regulating expression of the transcription factor LXRα, removal of which recapitulated the loss of Kupffer cell identity and disappearance. Thus, ZEB2 expression is required in macrophages to preserve their tissue-specific identities.
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•ZEB2 is highly expressed across the macrophage lineage•ZEB2 preserves the tissue-specific identities of macrophages across tissues•ZEB2 deficient macrophages are outcompeted by WT counterparts•LXRα is crucial for Kupffer cell identity and is maintained by ZEB2
Scott et al. demonstrate that ZEB2 is critical for maintaining the tissue identities of macrophages. Loss of ZEB2 results in tissue-specific changes in different macrophage populations and their subsequent disappearance. In Kupffer cells, ZEB2 maintains LXRα expression, loss of which reproduces the change in Kupffer cell identity and their disappearance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
School and college reopening-closure policies are considered one of the most promising non-pharmaceutical interventions for mitigating infectious diseases. Nonetheless, the effectiveness of these ...policies is still debated, largely due to the lack of empirical evidence on behavior during implementation. We examined U.S. college reopenings' association with changes in human mobility within campuses and in COVID-19 incidence in the counties of the campuses over a twenty-week period around college reopenings in the Fall of 2020. We used an integrative framework, with a difference-in-differences design comparing areas with a college campus, before and after reopening, to areas without a campus and a Bayesian approach to estimate the daily reproductive number (R.sub.t). We found that college reopenings were associated with increased campus mobility, and increased COVID-19 incidence by 4.9 cases per 100,000 (95% confidence interval CI: 2.9-6.9), or a 37% increase relative to the pre-period mean. This reflected our estimate of increased transmission locally after reopening. A greater increase in county COVID-19 incidence resulted from campuses that drew students from counties with high COVID-19 incidence in the weeks before reopening (X.sup.2 (2) = 8.9, p = 0.012) and those with a greater share of college students, relative to population (X.sup.2 (2) = 98.83, p < 0.001). Even by Fall of 2022, large shares of populations remained unvaccinated, increasing the relevance of understanding non-pharmaceutical decisions over an extended period of a pandemic. Our study sheds light on movement and social mixing patterns during the closure-reopening of colleges during a public health threat, and offers strategic instruments for benefit-cost analyses of school reopening/closure policies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sleep‐disordered breathing—comprising obstructive sleep apnoea (OSA), central sleep apnoea (CSA), or a combination of the two—is found in over half of heart failure (HF) patients and may have harmful ...effects on cardiac function, with swings in intrathoracic pressure (and therefore preload and afterload), blood pressure, sympathetic activity, and repetitive hypoxaemia. It is associated with reduced health‐related quality of life, higher healthcare utilization, and a poor prognosis. Whilst continuous positive airway pressure (CPAP) is the treatment of choice for patients with daytime sleepiness due to OSA, the optimal management of CSA remains uncertain. There is much circumstantial evidence that the treatment of OSA in HF patients with CPAP can improve symptoms, cardiac function, biomarkers of cardiovascular disease, and quality of life, but the quality of evidence for an improvement in mortality is weak. For systolic HF patients with CSA, the CANPAP trial did not demonstrate an overall survival or hospitalization advantage for CPAP. A minute ventilation‐targeted positive airway therapy, adaptive servoventilation (ASV), can control CSA and improves several surrogate markers of cardiovascular outcome, but in the recently published SERVE‐HF randomized trial, ASV was associated with significantly increased mortality and no improvement in HF hospitalization or quality of life. Further research is needed to clarify the therapeutic rationale for the treatment of CSA in HF. Cardiologists should have a high index of suspicion for sleep‐disordered breathing in those with HF, and work closely with sleep physicians to optimize patient management.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
SDSS J092609.45+334304.1: a nearby unevolved galaxy Pustilnik, S. A.; Tepliakova, A. L.; Kniazev, A. Y. ...
Monthly notices of the Royal Astronomical Society,
01/2010, Volume:
401, Issue:
1
Journal Article
Peer reviewed
Open access
We present the results of observations of the very low surface brightness (VLSB) dwarf galaxy SDSS J092609.45+334304.1 with extreme parameters which indicate its unevolved status. Namely, its value ...of O/H, derived as an average of that in two adjacent H ii regions at the NE edge of the disc, corresponds to the parameter 12 + log(O/H) = 7.12 ± 0.02, which is amongst the two lowest known. The total H i flux measurement obtained with the Nançay Radio Telescope and the photometric results implies that the galaxy ratio M(H i)/L
B∼ 3.0 is among the top known in the Local Volume. The galaxy is situated in the region of a nearby underdense region known as the Lynx-Cancer void, where other unevolved galaxies, including DDO 68, HS 0832+3542 and SAO 0822+3545, are known to be present. The total mass of this almost edge-on VLSB galaxy is ∼8.3 times larger than its baryonic mass, implying the dynamical dominance of dark matter (DM) halo. The (u−g), (g−r) colours of the outer parts of this galaxy are consistent with the ages of its main stellar population of 1-3 Gyr. Thanks to the galaxy isolation, the small effect of current or recent star formation, its proximity and rather large H i flux (∼2.5 Jy km s−1), this VLSB dwarf is a good laboratory for the detailed study of DM halo properties through H i kinematics and the star formation processes in very metal-poor low surface density environment. This finding, along with the discovery of other unusual dwarf galaxies in this void, provides evidence of the relation between galaxy evolution and its very low-density environment for the baryonic mass range of 108 to 109 M⊙. This relation seems to be consistent with that expected in the Λ cold dark matter models of galaxy and structure formation.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
We present an overview of opto-electronic characterization techniques for solar cells including light-induced charge extraction by linearly increasing voltage, impedance spectroscopy, transient ...photovoltage, charge extraction and more. Guidelines for the interpretation of experimental results are derived based on charge drift-diffusion simulations of solar cells with common performance limitations. It is investigated how nonidealities like charge injection barriers, traps and low mobilities among others manifest themselves in each of the studied cell characterization techniques. Moreover, comprehensive parameter extraction for an organic bulk-heterojunction solar cell comprising PCDTBT:PC
70
BM is demonstrated. The simulations reproduce measured results of 9 different experimental techniques. Parameter correlation is minimized due to the combination of various techniques. Thereby a route to comprehensive and accurate parameter extraction is identified.
The last 6000
years are of particular interest to the understanding of the Earth System because the boundary conditions of the climate system did not change dramatically (in comparison to larger ...glacial–interglacial changes), and because abundant, detailed regional palaeoclimatic proxy records cover this period. We use selected proxy-based reconstructions of different climate variables, together with state-of-the-art time series of natural forcings (orbital variations, solar activity variations, large tropical volcanic eruptions, land cover and greenhouse gases), underpinned by results from General Circulation Models (GCMs) and Earth System Models of Intermediate Complexity (EMICs), to establish a comprehensive explanatory framework for climate changes from the Mid-Holocene (MH) to pre-industrial time. The redistribution of solar energy, due to orbital forcing on a millennial timescale, was the cause of a progressive southward shift of the Northern Hemisphere (NH) summer position of the Intertropical Convergence Zone (ITCZ). This was accompanied by a pronounced weakening of the monsoon systems in Africa and Asia and increasing dryness and desertification on both continents. The associated summertime cooling of the NH, combined with changing temperature gradients in the world oceans, likely led to an increasing amplitude of the El Niño Southern Oscillation (ENSO) and, possibly, increasingly negative North Atlantic Oscillation (NAO) indices up to the beginning of the last millennium. On decadal to multi-century timescales, a worldwide coincidence between solar irradiance minima, tropical volcanic eruptions and decadal to multi-century scale cooling events was not found. However, reconstructions show that widespread decadal to multi-century scale cooling events, accompanied by advances of mountain glaciers, occurred in the NH (e.g., in Scandinavia and the European Alps). This occurred namely during the Little Ice Age (LIA) between AD ∼1350 and 1850, when the lower summer insolation in the NH, due to orbital forcing, coincided with solar activity minima and several strong tropical volcanic eruptions. The role of orbital forcing in the NH cooling, the southward ITCZ shift and the desertification of the Sahara are supported by numerous model simulations. Other simulations have suggested that the fingerprint of solar activity variations should be strongest in the tropics, but there is also evidence that changes in the ocean heat transport took place during the LIA at high northern latitudes, with possible additional implications for climates of the Southern Hemisphere (SH).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Tumor associated inflammation predicts response to immune checkpoint blockade in human melanoma. Current theories on regulation of inflammation center on anti-tumor T cell responses. Here we show ...that tumor associated B cells are vital to melanoma associated inflammation. Human B cells express pro- and anti-inflammatory factors and differentiate into plasmablast-like cells when exposed to autologous melanoma secretomes in vitro. This plasmablast-like phenotype can be reconciled in human melanomas where plasmablast-like cells also express T cell-recruiting chemokines CCL3, CCL4, CCL5. Depletion of B cells in melanoma patients by anti-CD20 immunotherapy decreases tumor associated inflammation and CD8
T cell numbers. Plasmablast-like cells also increase PD-1
T cell activation through anti-PD-1 blockade in vitro and their frequency in pretherapy melanomas predicts response and survival to immune checkpoint blockade. Tumor associated B cells therefore orchestrate and sustain melanoma inflammation and may represent a predictor for survival and response to immune checkpoint blockade therapy.
Chemotherapeutic agents are widely used for cancer treatment. In addition to their direct cytotoxic effects, these agents harness the host's immune system, which contributes to their antitumor ...activity. Here we show that two clinically used chemotherapeutic agents, gemcitabine (Gem) and 5-fluorouracil (5FU), activate the NOD-like receptor family, pyrin domain containing-3 protein (Nlrp3)-dependent caspase-1 activation complex (termed the inflammasome) in myeloid-derived suppressor cells (MDSCs), leading to production of interleukin-1β (IL-1β), which curtails anticancer immunity. Chemotherapy-triggered IL-1β secretion relied on lysosomal permeabilization and the release of cathepsin B, which bound to Nlrp3 and drove caspase-1 activation. MDSC-derived IL-1β induced secretion of IL-17 by CD4(+) T cells, which blunted the anticancer efficacy of the chemotherapy. Accordingly, Gem and 5FU exerted higher antitumor effects when tumors were established in Nlrp3(-/-) or Casp1(-/-) mice or wild-type mice treated with interleukin-1 receptor antagonist (IL-1Ra). Altogether, these results identify how activation of the Nlrp3 inflammasome in MDSCs by 5FU and Gem limits the antitumor efficacy of these chemotherapeutic agents.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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