Hierarchical Multi-Agent Reinforcement Learning for Air Combat Maneuvering

The application of artificial intelligence to simulate air-to-air combat scenarios is attracting increasing attention. To date the high-dimensional state and action spaces, the high complexity of situation information (such as imperfect and filtered information, stochasticity, incomplete knowledge about mission targets) and the nonlinear flight dynamics pose significant challenges for accurate air combat decision-making. These challenges are exacerbated when multiple heterogeneous agents are involved. We propose a hierarchical multi-agent reinforcement learning framework for air-to-air combat with multiple heterogeneous agents. In our framework, the decision-making process is divided into two stages of abstraction, where heterogeneous low-level policies control the action of individual units, and a high-level commander policy issues macro commands given the overall mission targets. Low-level policies are trained for accurate unit combat control. Their training is organized in a learning curriculum with increasingly complex training scenarios and league-based self-play. The commander policy is trained on mission targets given pre-trained low-level policies. The empirical validation advocates the advantages of our design choices.Comment: 22nd International Conference on Machine Learning and Applications (ICMLA 23

Emberger Syndrome – A Family History Over 3 Generations

# Introduction Haploinsufficiency of _GATA2_ leads to impaired genesis and function of hematopoietic stem and progenitor cells, resulting in impairment of all subsequent blood cell lineages. Germline mutations in _GATA2_ are transmitted by autosomal-dominant inheritance. Leading clinical symptoms of _GATA2_ deficiency syndromes are immunodeficiency, infections (mainly nontuberculous mycobacteria and human papillomavirus), predisposition to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), pulmonary alveolar proteinosis (PAP) and primary lymphedema. _GATA2_ mutations underlie not only Emberger syndrome (primary lymphedema and MDS), but also other syndromes like monocytopenia and mycobacterial infections syndrome (MonoMAC), dendritic cell/monocytopenia/natural killer (NK)-cell/B-cell lymphoid deficiency (DCML) and familial MDS/AML syndrome. We report the history of a Swiss family with Emberger syndrome extending over three generations. In addition, a review of the literature on _GATA2_ deficiencies is provided. # Methods Based on a general practitioner's observation of father and son sharing similar declined blood values and lymphedema, we examined the whole family for the presence of _GATA2_ mutation and a possible genotype-phenotype correlation. Publications on _GATA2_ deficiencies were researched on the PubMed database. # Results Six family members were diagnosed with _GATA2_ mutation, demonstrating individually variable penetrance and diversity of leading symptoms. # Conclusion Careful investigation of personal and family history, as well as meticulous examination, led to suspicion of the rare diagnosis of familial Emberger syndrome. Early diagnosis is mandatory for appropriate disease management

Gene drives: benefits, risks, and possible applications

Gene drives are genetic elements in sexually reproducing organisms that skew the pattern of inheritance of a given characteristic. They can be used to spread a characteristic that can alter or even reduce the numbers of individuals in wild populations of a certain species. As they spread by being inherited from one generation to the next, they could persist in populations long-term. The spreading property of gene drives could be a source of great potential in areas as diverse as the control of disease vectors, invasive species, agricultural pests and predators of endangered species. However, the same property may make containment challenging and therefore may also pose novel envi- ronmental risks. The evaluation, distribution of risks and benefits and the fact that gene drives may be seen as a particularly profound interference with nature further raises novel ethical considerations

Analysis and Functional Consequences of Increased Fab-Sialylation of Intravenous Immunoglobulin (IVIG) after Lectin Fractionation

It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG) might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA) lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1) or acidified lactose (E2) were analyzed for total IgG, F(ab’)2 and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2); again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10%) of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation

Localization of γ-Glutamylcysteine Synthetase and Glutathione Synthetase Activity in Maize Seedlings

Fresh weight, protein, cysteine, γ-glutamylcysteine, glutathione, and the extractable activity of the enzymes of glutathione biosynthesis, γ-glutamylcysteine synthetase (EC 6.3.2.2) and glutathione synthetase (EC 6.3.2.3), were measured in roots, scutella, endosperms, and shoots of 3-, 7-, and 11-d-old maize (Zea mays L. cv LG 9) seedlings. In 3-d-old seedlings, the scutella represented 14% of the seedling fresh weight, containing 43% of total protein and 63 and 55% of the activity of [gamma]-glutamylcysteine synthetase and glutathione synthetase, respectively; in 11-d-old seedlings, the corresponding values were 4.5% for fresh weight, 8.0% for protein content, and 14 and 20% for the enzyme activities. The highest concentrations of thiols were found for cysteine (0.27 mM) in the roots, for glutathione (4.4 mM) in the shoots, and for γ-glutamylcysteine (13 [mu]M) in the scutella of 3-d-old seedlings. The enzyme activities of roots were localized in subcellular fractions after sucrose density gradient centrifugation. Nearly half of the γ-glutamylcysteine synthetase activity was detected in the root proplastids of 4-d-old seedlings, whereas <10% of the glutathione synthetase activity was localized in this organelle. Our results demonstrate the importance of scutella in glutathione synthesis in the early stage of seedling development. Unlike chloroplasts, root plastids show only a small proportion of glutathione synthetase activity

Effect of Cadmium and/or Removal of Kernels or Shoots on the Levels of Cysteine, y-Glutamyl-cysteine, Glutathione, and TCA-soluble Thiols in Maize Seedlings

Six day old maize seedlings (Zea mays L.) were exposed as intact plants (A), after the removal of kernels (B) or shoots (C) or after the removal of kernels and transfer into the dark (D) to 0 or 50 micromolar cadmium for 2 days. The roots were analyzed for fresh weight, total TCA-soluble thiols (including phytochelatins), glutathione, and its precursor compounds cysteine and gamma-glutamyl-cysteine. With all treatments, cadmium caused an increase in the contents of cysteine, gamma-glutamyl-cysteine and total TCA-soluble thiols and a decrease in glutathione content. Our data indicate that the roots are at least in part autonomous to provide the thiols required for phytochelatin synthesis

Effect of Cadmium on γ-Glutamylcysteine Synthesis in Maize Seedlings

Cysteine, γ-glutamylcysteine, and glutathione and the extractable activity of the enzymes of glutathione biosynthesis, γ-glutamylcysteine synthetase (EC 6.3.2.2) and glutathione synthetase (EC 6.3.2.3), were measured in roots and leaves of maize seedlings (Zea mays L. cv LG 9) exposed to CdCl(2) concentrations up to 200 micromolar. At 50 micromolar Cd(2+), γ-glutamylcysteine contents increased continuously during 4 days up to 21-fold and eightfold of the control in roots and leaves, respectively. Even at 0.5 micromolar Cd(2+), the concentration of γ-glutamylcysteine in the roots was significantly higher than in the control. At 5 micromolar and higher Cd(2+) concentrations, a significant increase in γ-glutamylcysteine synthetase activity was measured in the roots, whereas in the leaves this enzyme activity was enhanced only at 200 micromolar Cd(2+). Labeling of isolated roots with [(35)S]sulfate showed that both sulfate assimilation and glutathione synthesis were increased by Cd. The accumulation of γ-glutamylcysteine in the roots did not affect the root exudation rate of this compound. Our results indicate that maize roots are at least in part autonomous in providing the additional thiols required for phytochelatin synthesis induced by Cd