Photonic crystals for light-emitting devices

Photonic crystals or photonic bandgap (PBG) structures promise to revolutionize optoelectronics by making anew class of highly efficient, low noise light emitters possible. We present data to show that their properties, in particular 2D systems, have now been fully characterized in the relevant semiconductor material system and at near-IR wavelengths, so effort can be redirected towards making active light emitters. As a first example, we present a semiconductor laser with one output mirror designed according to PBG principles. From threshold and efficiency data, we derive a reflectivity of 95 +/- 10 percent for this mirror, which underlines the viability of the PBG approach for practical devices. In order to realize the full potential of photonic crystal light emitters, however, important material issues need to be considered. Non- radiative recombination, for example, is a big problem when the photonic crystal is an integral part of the active region because of the relatively large areas of exposed surface. Several possible solutions to this problem are presented

Gallstones, cholecystectomy and kidney cancer: observational and Mendelian randomisation results based on large cohorts.

BACKGROUND AND AIMS Gallstones (cholelithiasis) constitute a major health burden with high costs related to surgical removal of the gallbladder (cholecystectomy), generally indicated for symptomatic gallstones. The association between gallstones, cholecystectomy and kidney cancer is controversial. We comprehensively investigated this association, considering age at cholecystectomy and time from cholecystectomy to kidney cancer diagnosis, and assessing the causal effect of gallstones on kidney cancer risk by Mendelian randomisation (MR). METHODS We compared the risk of kidney cancer in cholecystectomised and non-cholecystectomised individuals (16.6 million in total) from the Swedish nationwide cancer, census, patient and death registries using hazard ratios (HRs). For two-sample and multivariable MR, we used summary statistics based on 408,567 UK Biobank participants. RESULTS During a median follow-up of 13 years, 2,627 of 627,870 cholecystectomised Swedish patients developed kidney cancer (HR=1.17, 95% CI 1.12-1.22). Kidney cancer risk was particularly increased in the first 6 months after cholecystectomy (HR=3.79, 95% CI 3.18-4.52) and in patients cholecystectomised before age 40 (HR=1.55, 95% CI 1.39-1.72). MR results based on 18.417 gallstone and 1,788 kidney cancer patients from the UK revealed a causal effect of gallstones on kidney cancer risk (9.6% risk increase per doubling in gallstone prevalence, 95% CI 1.2%-18.8%). CONCLUSIONS Both observational and causal MR estimates based on large prospective cohorts support an increased risk of kidney cancer in gallstone patients. Our findings provide solid evidence for the compelling need to diagnostically rule out kidney cancer before and during gallbladder removal, to prioritise kidney cancer screening in patients undergoing cholecystectomy in their 30s, and to investigate the underlying mechanisms linking gallstones and kidney cancer in future studies

Creating and Capturing Artificial Emotions in Autonomous Robots and Software Agents

This paper presents ARTEMIS, a control system for autonomous robots or software agents. ARTEMIS is able to create and capture artificial emotions during interactions with its environment, and we describe the underlying mechanisms for this. The control system also realizes the capturing of knowledge about its past artificial emotions. A specific interpretation of a knowledge graph, called an Agent Knowledge Graph, represents these artificial emotions. For this, we devise a formalism which enriches the traditional factual knowledge in knowledge graphs with the representation of artificial emotions. As proof of concept, we realize a concrete software agent based on the ARTEMIS control system. This software agent acts as a user assistant and executes the user’s orders. The environment of this user assistant consists of autonomous service agents. The execution of user’s orders requires interaction with these autonomous service agents. These interactions lead to artificial emotions within the assistant. The first experiments show that it is possible to realize an autonomous agent with plausible artificial emotions with ARTEMIS and to record these artificial emotions in its Agent Knowledge Graph. In this way, autonomous agents based on ARTEMIS can capture essential knowledge that supports successful planning and decision making in complex dynamic environments and surpass emotionless agents

Photonic crystals for light-emitting devices

Photonic crystals or photonic bandgap (PBG) structures promise to revolutionize optoelectronics by making anew class of highly efficient, low noise light emitters possible. We present data to show that their properties, in particular 2D systems, have now been fully characterized in the relevant semiconductor material system and at near-IR wavelengths, so effort can be redirected towards making active light emitters. As a first example, we present a semiconductor laser with one output mirror designed according to PBG principles. From threshold and efficiency data, we derive a reflectivity of 95 +/- 10 percent for this mirror, which underlines the viability of the PBG approach for practical devices. In order to realize the full potential of photonic crystal light emitters, however, important material issues need to be considered. Non- radiative recombination, for example, is a big problem when the photonic crystal is an integral part of the active region because of the relatively large areas of exposed surface. Several possible solutions to this problem are presented

Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium

The HMG-box transcription factor Sox9 is expressed in the intestinal epithelium, specifically, in stem/progenitor cells and in Paneth cells. Sox9 expression requires an active β-catenin–Tcf complex, the transcriptional effector of the Wnt pathway. This pathway is critical for numerous aspects of the intestinal epithelium physiopathology, but processes that specify the cell response to such multipotential signals still remain to be identified. We inactivated the Sox9 gene in the intestinal epithelium to analyze its physiological function. Sox9 inactivation affected differentiation throughout the intestinal epithelium, with a disappearance of Paneth cells and a decrease of the goblet cell lineage. Additionally, the morphology of the colon epithelium was severely altered. We detected general hyperplasia and local crypt dysplasia in the intestine, and Wnt pathway target genes were up-regulated. These results highlight the central position of Sox9 as both a transcriptional target and a regulator of the Wnt pathway in the regulation of intestinal epithelium homeostasis

A peripheral epigenetic signature of immune system genes is linked to neocortical thickness and memory

Increasing age is tightly linked to decreased thickness of the human neocortex. The biological mechanisms that mediate this effect are hitherto unknown. The DNA methylome, as part of the epigenome, contributes significantly to age-related phenotypic changes. Here, we identify an epigenetic signature that is associated with cortical thickness (P=3.86 × 10(-8)) and memory performance in 533 healthy young adults. The epigenetic effect on cortical thickness was replicated in a sample comprising 596 participants with major depressive disorder and healthy controls. The epigenetic signature mediates partially the effect of age on cortical thickness (P<0.001). A multilocus genetic score reflecting genetic variability of this signature is associated with memory performance (P=0.0003) in 3,346 young and elderly healthy adults. The genomic location of the contributing methylation sites points to the involvement of specific immune system genes. The decomposition of blood methylome-wide patterns bears considerable potential for the study of brain-related traits

Climate affects neighbour‐induced changes in leaf chemical defences and tree diversity‐herbivory relationships

1. Associational resistance theory predicts that insect herbivory decreases with increasing tree diversity in forest ecosystems. However, the generality of this effect and its underlying mechanisms are still debated, particularly since evidence has accumulated that climate may influence the direction and strength of the relationship between diversity and herbivory. 2. We quantified insect leaf herbivory and leaf chemical defences (phenolic compounds) of silver birch Betula pendula in pure and mixed plots with different tree species composition across 12 tree diversity experiments in different climates. We investigated whether the effects of neighbouring tree species diversity on insect herbivory in birch, that is, associational effects, were dependent on the climatic context, and whether neighbour-induced changes in birch chemical defences were involved in associational resistance to insect herbivory. 3. We showed that herbivory on birch decreased with tree species richness (i.e. associational resistance) in colder environments but that this relationship faded as mean annual temperature increased. 4. Birch leaf chemical defences increased with tree species richness but decreased with the phylogenetic distinctiveness of birch from its neighbours, particularly in warmer and more humid environments

Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data

BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10−5) and Europeans (P = 9 × 10−5). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10−6). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk. (Hepatology 2021;73:1783-1796).Fil: Barahona Ponce, Carol. Ruprecht Karls Universitat Heidelberg; Alemania. Universidad de Chile; ChileFil: Scherer, Dominique. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Brinster, Regina. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Boekstegers, Felix. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Marcelain, Katherine. Universidad de Chile; ChileFil: Gárate Calderón, Valentina. Ruprecht Karls Universitat Heidelberg; Alemania. Universidad de Chile; ChileFil: Müller, Bettina. Instituto Nacional del Cáncer; ChileFil: de Toro, Gonzalo. Hospital Puerto Montt; Chile. Universidad Austral de Chile; ChileFil: Retamales, Javier. Instituto Nacional del Cáncer; ChileFil: Barajas, Olga. Universidad de Chile; ChileFil: Ahumada, Monica. Universidad de Chile; ChileFil: Morales, Erik. Hospital Regional de Talca; Chile. Universidad Católica del Maule; ChileFil: Rojas, Armando. Universidad Católica del Maule; ChileFil: Sanhueza, Verónica. Hospital Padre Hurtado; ChileFil: Loader, Denisse. Hospital Padre Hurtado; ChileFil: Rivera, María Teresa. Hospital del Salvador; ChileFil: Gutiérrez, Lorena. Hospital San Juan de Dios; ChileFil: Bernal, Giuliano. Universidad Católica del Norte; ChileFil: Ortega, Alejandro. Hospital Regional; ChileFil: Montalvo, Domingo. Hospital Regional Juan Noé Crevani; ChileFil: Portiño, Sergio. Universidad de Chile; ChileFil: Bertrán, Maria Enriqueta. Ministerio de Salud; ChileFil: Gabler, Fernando. Universidad de Santiago de Chile. Hospital Clinico San Borja Arriaran; ChileFil: Spencer, Loreto. Hospital Regional Guillermo Grant Benavente; ChileFil: Olloquequi, Jordi. Universidad Autónoma de Chile; ChileFil: Fischer, Christine. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Jenab, Mazda. International Agency For Research On Cancer; AlemaniaFil: Aleksandrova, Krasimira. German Institute Of Human Nutrition; AlemaniaFil: Katzke, Verena. German Cancer Research Center; AlemaniaFil: Gonzalez-Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentin

Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations

Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin’s chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68–0.86; rs1105879 OR = 0.77 95% CI = 0.69–0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer risk