Soziale Kontrolle der Homosexualität: die höchstrichterliche Tatbestandsauslegung zur widernatürlichen Unzucht im Lichte sexualwissenschaftlicher Forschung

Die historische Rekonstruktion kollektiver Deutungsmuster sexuellen Verhaltens und abweichender Sexualität ergibt, daß sich Veränderungen in den Denkmustern der Wissenschaftsgemeinde nur langsam und kaum merklich vollziehen. Das Zusammenspiel zwischen der Rechtswissenschaft und der sich im 19. Jahrhundert etablierenden Sexualwissenschaft zeigt, daß auch heute noch Zweifel anzumelden sind, wenn Wissenschaftler ihre Erkenntnisse als neutrale Denkkonzepte darstellen. Die Rechtswissenschaft hat aus der Flut sexualpsychiatrischer Erkenntnisse diejenigen ausgewählt, welche die soziale Kontrolle mann-männlicher Geschlechtsakte perfektionieren konnte. Dies wird beispielhaft anhand der höchstrichterlichen Rechtsprechung zum Tatbestand der widernatürlichen Unzucht gezeigt. Indem die Rechtsprechung im 19. Jahrhundert implizit der psychiatrischen Definition von Sexualität folgte, faßte sie immer mehr gleichgeschlechtliche Verhaltensweisen unter den dehnbaren Tatbestandsbegriff der widernatürlichen Unzucht zusammen und sanktionierte sie damit. (pka

Towards Automated Design of Riboswitches

Experimental screening and selection pipelines for the discovery of novel riboswitches are expensive, time-consuming, and inefficient. Using computational methods to reduce the number of candidates for the screen could drastically decrease these costs. However, existing computational approaches do not fully satisfy all requirements for the design of such initial screening libraries. In this work, we present a new method, libLEARNA, capable of providing RNA focus libraries of diverse variable-length qualified candidates. Our novel structure-based design approach considers global properties as well as desired sequence and structure features. We demonstrate the benefits of our method by designing theophylline riboswitch libraries, following a previously published protocol, and yielding 30% more unique high-quality candidates.Comment: 9 pages, Accepted at the 2023 ICML Workshop on Computational Biolog

Why Do Machine Learning Practitioners Still Use Manual Tuning? A Qualitative Study

Current advanced hyperparameter optimization (HPO) methods, such as Bayesian optimization, have high sampling efficiency and facilitate replicability. Nonetheless, machine learning (ML) practitioners (e.g., engineers, scientists) mostly apply less advanced HPO methods, which can increase resource consumption during HPO or lead to underoptimized ML models. Therefore, we suspect that practitioners choose their HPO method to achieve different goals, such as decrease practitioner effort and target audience compliance. To develop HPO methods that align with such goals, the reasons why practitioners decide for specific HPO methods must be unveiled and thoroughly understood. Because qualitative research is most suitable to uncover such reasons and find potential explanations for them, we conducted semi-structured interviews to explain why practitioners choose different HPO methods. The interviews revealed six principal practitioner goals (e.g., increasing model comprehension), and eleven key factors that impact decisions for HPO methods (e.g., available computing resources). We deepen the understanding about why practitioners decide for different HPO methods and outline recommendations for improvements of HPO methods by aligning them with practitioner goals

Immune Checkpoint Function of CD85j in CD8 T Cell Differentiation and Aging

Aging is associated with an increased susceptibility to infection and a failure to control latent viruses thought to be driven, at least in part, by alterations in CD8 T cell function. The aging T cell repertoire is characterized by an accumulation of effector CD8 T cells, many of which express the negative regulatory receptor CD85j. To define the biological significance of CD85j expression on CD8 T cells and to address the question whether presence of CD85j in older individuals is beneficial or detrimental for immune function, we examined the specific attributes of CD8 T cells expressing CD85j as well as the functional role of CD85j in antigen-specific CD8 T cell responses during immune aging. Here, we show that CD85j is mainly expressed by terminally differentiated effector (TEMRAs) CD8 T cells, which increase with age, in cytomegalovirus (CMV) infection and in males. CD85j+ CMV-specific cells demonstrate clonal expansion. However, TCR diversity is similar between CD85j+ and CD85j− compartments, suggesting that CD85j does not directly impact the repertoire of antigen-specific cells. Further phenotypic and functional analyses revealed that CD85j identifies a specific subset of CMV-responsive CD8 T cells that coexpress a marker of senescence (CD57) but retain polyfunctional cytokine production and expression of cytotoxic mediators. Blocking CD85j binding enhanced proliferation of CMV-specific CD8 T cells upon antigen stimulation but did not alter polyfunctional cytokine production. Taken together, these data demonstrate that CD85j characterizes a population of “senescent,” but not exhausted antigen-specific effector CD8 T cells and indicates that CD85j is an important checkpoint regulator controlling expansion of virus-specific T cells during aging. Inhibition of CD85j activity may be a mechanism to promote stronger CD8 T cell effector responses during immune aging

Genomic deletion and promoter methylation status of Hypermethylated in Cancer 1 (HIC1) in mantle cell lymphoma

Mantle cell lymphomas (MCL), characterized by the t(11;14)(q13;q32), frequently carry secondary genetic alterations such as deletions in chromosome 17p involving the TP53 locus. Given that the association between TP53-deletions and concurrent mutations of the remaining allele is weak and based on our recent report that the Hypermethylated in Cancer 1 (HIC1) gene, that is located telomeric to the TP53 gene, may be targeted by deletions in 17p in diffuse large B-cell lymphoma (DLBCL), we investigated whether HIC1 inactivations might also occur in MCL. Monoallelic deletions of the TP53 locus were detected in 18 out of 59 MCL (31%), while overexpression of p53 protein occurred in only 8 out of 18 of these MCL (44%). In TP53-deleted MCL, the HIC1 gene locus was co-deleted in 11 out of 18 cases (61%). However, neither TP53 nor HIC1 deletions did affect survival of MCL patients. In most analyzed cases, no hypermethylation of the HIC1 exon 1A promoter was observed (17 out of 20, 85%). However, in MCL cell lines without HIC1-hypermethylation, the mRNA expression levels of HIC1 were nevertheless significantly reduced, when compared to reactive lymph node specimens, pointing to the occurrence of mechanisms other than epigenetic or genetic events for the inactivation of HIC1 in this entity

Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition

SummarySmoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant