The virial expansion of a classical interacting system

We consider N particles interacting pair-wise by an inverse square potential in one dimension (Calogero-Sutherland-Moser model). When trapped harmonically, its classical canonical partition function for the repulsive regime is known in the literature. We start by presenting a concise re-derivation of this result. The equation of state is then calculated both for the trapped and the homogeneous gas. Finally, the classical limit of Wu's distribution function for fractional exclusion statistics is obtained and we re-derive the classical virial expansion of the homogeneous gas using this distribution function.Comment: 9 pages; added references to some earlier work on this problem; this has led to a significant shortening of the paper and a changed titl

Exploring romantic need as part of mental health social care practice

The ability to form strong relationships is viewed as central to mental health recovery. Few studies have explored the experiences of people with mental health problems in forming or maintaining romantic relationships. Our study addressed this gap through conducting focus groups with ten people with mental health problems, six carers and six professionals. All three participant groups considered romantic relationships to be important aspects of wellbeing and lamented this gap in the lives of people with mental health problems. Service users and carers perceived the physicality and outward trappings of ‘being mentally ill,’ including treatment side effects and unemployment to impact negatively on romantic relationships. Service users reported self and societal stigma as a major barrier to relationships. Carers and professionals focused on vulnerability and risks. Professionals stated that they rarely supported people with mental health problems with their romantic relationships and were uneasy about discussing sexual intimacy

Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2

The Src homology 2 (SH2) domain recognizes phosphotyrosine (pY) post translational modifications in partner proteins to trigger downstream signaling. Drug discovery efforts targeting the SH2 domains have long been stymied by the poor drug-like properties of phosphate and its mimetics. Here, we use structure-based design to target the SH2 domain of the E3 ligase suppressor of cytokine signaling 2 (SOCS2). Starting from the highly ligand-efficient pY amino acid, a fragment growing approach reveals covalent modification of Cys111 in a co-crystal structure, which we leverage to rationally design a cysteine-directed electrophilic covalent inhibitor MN551. We report the prodrug MN714 containing a pivaloyloxymethyl (POM) protecting group and evidence its cell permeability and capping group unmasking using cellular target engagement and in-cell 19F NMR spectroscopy. Covalent engagement at Cys111 competitively blocks recruitment of cellular SOCS2 protein to its native substrate. The qualified inhibitors of SOCS2 could find attractive applications as chemical probes to understand the biology of SOCS2 and its CRL5 complex, and as E3 ligase handles in proteolysis targeting chimera (PROTACs) to induce targeted protein degradation.</p

Single cell analyses and machine learning define hematopoietic progenitor and HSC-like cells derived from human PSCs

Haematopoietic stem and progenitor cells (HSPCs) develop through distinct waves at various anatomical sites during embryonic development. The in vitro differentiation of human pluripotent stem cells (hPSCs) is able to recapitulate some of these processes, however, it has proven difficult to generate functional haematopoietic stem cells (HSCs). To define the dynamics and heterogeneity of HSPCs that can be generated in vitro from hPSCs, we exploited single cell RNA sequencing (scRNAseq) in combination with single cell protein expression analysis. Bioinformatics analyses and functional validation defined the transcriptomes of naïve progenitors as well as erythroid, megakaryocyte and leukocyte-committed progenitors and we identified CD44, CD326, ICAM2/CD9 and CD18 as markers of these progenitors, respectively. Using an artificial neural network (ANN), that we trained on a scRNAseq derived from human fetal liver, we were able to identify a wide range of hPSCs-derived HPSC phenotypes, including a small group classified as HSCs. This transient HSC-like population decreased as differentiation proceeded and was completely missing in the dataset that had been generated using cells selected on the basis of CD43expression. By comparing the single cell transcriptome of in vitro-generated HSC-like cells with those generated within the fetal liver we identified transcription factors and molecular pathways that can be exploited in the future to improve the in vitro production of HSCs

An Open Standard for Camera Trap Data

Camera traps that capture photos of animals are a valuable tool for monitoring biodiversity. The use of camera traps is rapidly increasing and there is an urgent need for standardization to facilitate data management, reporting and data sharing. Here we offer the Camera Trap Metadata Standard as an open data standard for storing and sharing camera trap data, developed by experts from a variety of organizations. The standard captures information necessary to share data between projects and offers a foundation for collecting the more detailed data needed for advanced analysis. The data standard captures information about study design, the type of camera used, and the location and species names for all detections in a standardized way. This information is critical for accurately assessing results from individual camera trapping projects and for combining data from multiple studies for meta-analysis. This data standard is an important step in aligning camera trapping surveys with best practices in data-intensive science. Ecology is moving rapidly into the realm of big data, and central data repositories are becoming a critical tool and are emerging for camera trap data. This data standard will help researchers standardize data terms, align past data to new repositories, and provide a framework for utilizing data across repositories and research projects to advance animal ecology and conservation

An Open Standard for Camera Trap Data

Camera traps that capture photos of animals are a valuable tool for monitoring biodiversity. The use of camera traps is rapidly increasing and there is an urgent need for standardization to facilitate data management, reporting and data sharing. Here we offer the Camera Trap Metadata Standard as an open data standard for storing and sharing camera trap data, developed by experts from a variety of organizations. The standard captures information necessary to share data between projects and offers a foundation for collecting the more detailed data needed for advanced analysis. The data standard captures information about study design, the type of camera used, and the location and species names for all detections in a standardized way. This information is critical for accurately assessing results from individual camera trapping projects and for combining data from multiple studies for meta-analysis. This data standard is an important step in aligning camera trapping surveys with best practices in data-intensive science. Ecology is moving rapidly into the realm of big data, and central data repositories are becoming a critical tool and are emerging for camera trap data. This data standard will help researchers standardize data terms, align past data to new repositories, and provide a framework for utilizing data across repositories and research projects to advance animal ecology and conservation

Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2

The Src homology 2 (SH2) domain recognises phosphotyrosine (pY) post translational modifications in partner proteins to trigger downstream signalling. Drug discovery efforts targeting the SH2 domains have long been stymied by the poor drug-like properties of phosphate and its mimetics. Here, we have used structure-based design to target the SH2 domain of the E3 ligase suppressor of cytokine signalling 2 (SOCS2). Starting from the highly ligand-efficient pY amino acid, a fragment growing approach led to a serendipitous observation of covalent modification of Cys111 in a co-crystal structure, which we leveraged to rationally design a cysteine-directed electrophilic covalent inhibitor MN551. We developed the prodrug MN714 containing a pivaloyloxymethyl (POM) protecting group and evidence its cell permeability and capping group unmasking using cellular target engagement and in cell 19F NMR spectroscopy. Covalent engagement and modification of Cys111 of cellular SOCS2 was confirmed using mass spectrometry. The qualified covalent inhibitors of SOCS2 could find attractive applications as chemical probes to understand the biology of SOCS2 and its CRL5 complex, and as covalent E3 ligase handles in proteolysis targeting chimera (PROTACs) to induce targeted protein degradation

Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2

Abstract The Src homology 2 (SH2) domain recognizes phosphotyrosine (pY) post translational modifications in partner proteins to trigger downstream signaling. Drug discovery efforts targeting the SH2 domains have long been stymied by the poor drug-like properties of phosphate and its mimetics. Here, we use structure-based design to target the SH2 domain of the E3 ligase suppressor of cytokine signaling 2 (SOCS2). Starting from the highly ligand-efficient pY amino acid, a fragment growing approach reveals covalent modification of Cys111 in a co-crystal structure, which we leverage to rationally design a cysteine-directed electrophilic covalent inhibitor MN551. We report the prodrug MN714 containing a pivaloyloxymethyl (POM) protecting group and evidence its cell permeability and capping group unmasking using cellular target engagement and in-cell 19F NMR spectroscopy. Covalent engagement at Cys111 competitively blocks recruitment of cellular SOCS2 protein to its native substrate. The qualified inhibitors of SOCS2 could find attractive applications as chemical probes to understand the biology of SOCS2 and its CRL5 complex, and as E3 ligase handles in proteolysis targeting chimera (PROTACs) to induce targeted protein degradation