107 research outputs found
Third order nonlinear susceptibility of InN at near band-gap wavelengths
The authors report room-temperature measurements of the third order nonlinear susceptibility modulus ∫ (3) ∫ of thick (∼600 nm) InN layers. Transmission measurements provide a room-temperature value for the optical band gap of the samples slightly above 1500 nm. Third order nonlinear optical susceptibility has been measured using degenerate four wave mixing experiments at wavelengths near and above band gap. ∫ (3) ∫ values of (4.2-10) × 10-10 esu were measured at this wavelength range. The associated relaxation time of the generated population grating at 1500 nm was measured. The obtained value of 4.8 ps is consistent with a nonradiative recombination mechanism. © 2007 American Institute of Physics.Peer Reviewe
Economic Impact of COVID-19 Pandemic on Dental Practices in Germany: A Cross-Sectional Survey.
An observational cross-sectional survey was planned and carried out to evaluate the economic impact of the SARS-CoV-2/COVID-19 pandemic on dental practices in Germany. An online-questionnaire was developed and previously calibrated by a group consisting of experts from dentists, lawyers, and business economists (n = 21; Intra-Class-Coefficient > 0.8). It consisted of four main categories: vital statistics, professional activity and practice structure, economic impact of the COVID-19 pandemic and validation and contextualization to avoid automated filling in. The questionnaire was administered anonymously to 9732 dentists in Germany, 4434 of whom opened it and 1496 of whom fully completed it. These results were evaluated and summarized. Respondents were divided into seven German economic macro areas. Difference in proportion among questionnaire items was evaluated with χ2 test or Fisher exact test appropriately. Linear trend analysis was performed among German macro areas. Ordinal multinomial linear regression analysis was run to evaluate the association with questionnaire items with respect to a collapse and/or quarantine measures due to a positive test/infection/disease of dental personnel or an increase in average monthly costs due to the pandemic. One-third experienced a collapse or quarantine measures of the predominantly self-employed participating dentists (92%). Small practices were less affected than larger ones. Average monthly costs increased sharply in all practice structures. The findings shall help to better manage future pandemics and provide information to policy makers. As the pandemic situation is still ongoing, the medium- and long-term economic impact should be further evaluated
Soothsaying DOM: A Current Perspective on the Future of Oceanic Dissolved Organic Carbon
The vast majority of freshly produced oceanic dissolved organic carbon (DOC) is derived from marine phytoplankton, then rapidly recycled by heterotrophic microbes. A small fraction of this DOC survives long enough to be routed to the interior ocean, which houses the largest and oldest DOC reservoir. DOC reactivity depends upon its intrinsic chemical composition and extrinsic environmental conditions. Therefore, recalcitrance is an emergent property of DOC that is analytically difficult to constrain. New isotopic techniques that track the flow of carbon through individual organic molecules show promise in unveiling specific biosynthetic or degradation pathways that control the metabolic turnover of DOC and its accumulation in the deep ocean. However, a multivariate approach is required to constrain current carbon fluxes so that we may better predict how the cycling of oceanic DOC will be altered with continued climate change. Ocean warming, acidification, and oxygen depletion may upset the balance between the primary production and heterotrophic reworking of DOC, thus modifying the amount and/or composition of recalcitrant DOC. Climate change and anthropogenic activities may enhance mobilization of terrestrial DOC and/or stimulate DOC production in coastal waters, but it is unclear how this would affect the flux of DOC to the open ocean. Here, we assess current knowledge on the oceanic DOC cycle and identify research gaps that must be addressed to successfully implement its use in global scale carbon models
Structure-guided identification of a family of dual receptor-binding PfEMP1 that is associated with cerebral malaria
Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria, a binding phenotype linked to its symptoms has not been identified. Here, we used structural biology to determine how a group of PfEMP1 proteins interacts with intercellular adhesion molecule 1 (ICAM-1), allowing us to predict binders from a specific sequence motif alone. Analysis of multiple Plasmodium falciparum genomes showed that ICAM-1-binding PfEMP1s also interact with endothelial protein C receptor (EPCR), allowing infected erythrocytes to synergistically bind both receptors. Expression of these PfEMP1s, predicted to bind both ICAM-1 and EPCR, is associated with increased risk of developing cerebral malaria. This study therefore reveals an important PfEMP1-binding phenotype that could be targeted as part of a strategy to prevent cerebral malaria
Modelling seawater carbonate chemistry in shellfish aquaculture regions: Insights into CO2 release associated with shell formation and growth
Mollusc aquaculture is a high-value industry that is increasing production rapidly in Europe and across the globe. In recent years, there has been discussion of the potential wide-ranging environmental benefits of this form of food production. One aspect of mollusc aquaculture that has received scrutiny is the production of calcareous shells (CaCO3). Mollusc shell growth has sometimes been described as a sink for atmospheric CO2, as it locks away carbon in solid mineral form. However, more rigorous carbonate chemistry modelling, including concurrent changes in seawater pCO2, pH, dissolved inorganic carbon, and total alkalinity, shows that calcification is a net CO2 source to the atmosphere. Combined with discussions about whether mollusc respiration should be included in carbon footprint modelling, this suggests that greater in-depth understanding is required before shellfish aquaculture can be included in carbon trading schemes and footprint calculations. Here, we show that regional differences in the marine carbonate system can alter the amount of CO2 released per unit CaCO3 formation. Our carbonate chemistry modelling shows that a coastal mussel farm in southern Portugal releases up to ~0.290 g of CO2 per g of CaCO3 shell formed. In comparison, an identical farm in the coastal Baltic Sea would produce up to 33% more CO2 per g of CaCO3 (~0.385 g-CO2·(g-CaCO3)−1). This spatial variability should therefore also be considered if mollusc aquaculture is to be included in future carbon trading schemes, and in planning future expansion of production across the industry
Extent and Causes of Chesapeake Bay Warming
Coastal environments such as the Chesapeake Bay have long been impacted by eutrophication stressors resulting from human activities, and these impacts are now being compounded by global warming trends. However, there are few studies documenting long-term estuarine temperature change and the relative contributions of rivers, the atmosphere, and the ocean. In this study, Chesapeake Bay warming, since 1985, is quantified using a combination of cruise observations and model outputs, and the relative contributions to that warming are estimated via numerical sensitivity experiments with a watershed–estuarine modeling system. Throughout the Bay’s main stem, similar warming rates are found at the surface and bottom between the late 1980s and late 2010s (0.02 +/- 0.02C/year, mean +/- 1 standard error), with elevated summer rates (0.04 +/- 0.01C/year) and lower rates of winter warming (0.01 +/- 0.01C/year). Most (~85%) of this estuarine warming is driven by atmospheric effects. The secondary influence of ocean warming increases with proximity to the Bay mouth, where it accounts for more than half of summer warming in bottom waters. Sea level rise has slightly reduced summer warming, and the influence of riverine warming has been limited to the heads of tidal tributaries. Future rates of warming in Chesapeake Bay will depend not only on global atmospheric trends, but also on regional circulation patterns in mid-Atlantic waters, which are currently warming faster than the atmosphere.
Supporting model data available at: https://doi.org/10.25773/c774-a36
MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I.
Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated inflammatory response in tumors that undergo stemness- and senescence-associated reprogramming. In these tumor cells, activation of the innate immunity sensor RIG-I via its agonist IVT4, triggers an interferon and a pro-apoptotic response that synergize with concomitant kinase inhibition. In humanized lung cancer xenografts and a syngeneic Egfr-driven lung cancer model these effects translate into reduction of exhausted CD8+ T cells and robust tumor shrinkage. Overall, the mechanistic understanding of MAPK/IRF1-mediated intratumoral reprogramming may ultimately prolong the efficacy of targeted drugs in genetically defined cancer patients
Clonal dynamics of BRAF-driven drug resistance in EGFR-mutant lung cancer
Activation of MAPK signaling via BRAF mutations may limit the activity of EGFR inhibitors in EGFR-mutant lung cancer patients. However, the impact of BRAF mutations on the selection and fitness of emerging resistant clones during anti-EGFR therapy remains elusive. We tracked the evolution of subclonal mutations by whole-exome sequencing and performed clonal analyses of individual metastases during therapy. Complementary functional analyses of polyclonal EGFR-mutant cell pools showed a dose-dependent enrichment of BRAF(V600E) and a loss of EGFR inhibitor susceptibility. The clones remain stable and become vulnerable to combined EGFR, RAF, and MEK inhibition. Moreover, only osimertinib/trametinib combination treatment, but not monotherapy with either of these drugs, leads to robust tumor shrinkage in EGFR-driven xenograft models harboring BRAF mutations. These data provide insights into the dynamics of clonal evolution of EGFR-mutant tumors and the therapeutic implications of BRAF(V600E) co-mutations that may facilitate the development of treatment strategies to improve the prognosis of these patients
MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I
Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated inflammatory response in tumors that undergo stemness- and senescence-associated reprogramming. In these tumor cells, activation of the innate immunity sensor RIG-I via its agonist IVT4, triggers an interferon and a pro-apoptotic response that synergize with concomitant kinase inhibition. In humanized lung cancer xenografts and a syngeneic Egfr-driven lung cancer model these effects translate into reduction of exhausted CD8(+) T cells and robust tumor shrinkage. Overall, the mechanistic understanding of MAPK/IRF1-mediated intratumoral reprogramming may ultimately prolong the efficacy of targeted drugs in genetically defined cancer patients
Erratum to: Methods for evaluating medical tests and biomarkers
[This corrects the article DOI: 10.1186/s41512-016-0001-y.]
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