Biology subjects

Sor, R.

Publications and source records attributed to Sor, R..

3 recordsLinked to original sources

bioRxiv2026

PAMalytics: a no-code application for structured validation of bioacoustic detections

1. Passive acoustic monitoring (PAM) is increasingly used for ecological research, biodiversity monitoring, assessment, and reporting. Automated species classifiers make it feasible to process large audio datasets but generate numerous detections that often need validation before use in downstream analyses or formal outputs. 2. Method development in PAM has focused on classifier building and downstream models that account for imperfect detection, yet the practical step between these - post-classification validation - remains weakly supported and is often implemented through ad hoc workflows. This increases manual handling, creates scope for transcription or consolidation errors, limits transparency and makes it difficult to document what was reviewed. 3. We introduce PAMalytics, an open-source, no-code, local browser-based application to support post-classification validation as a standardised workflow stage. PAMalytics ingests detections from any classifier, allows users to define how detections are sampled for review, and presents selected detections alongside their spectrograms with audio playback in one unified interface. Sampling strategy and review decisions are tracked alongside reviewer identity improving traceability and reproducibility across the validation workflow. 4. Case studies with Conservation International Cambodia and Imperial College London demonstrate PAMalytics in two validation settings. In Cambodia, gibbon predictions from a large, uneven dataset were sampled within sites, with likely classifier errors prioritised for validation. At Imperial, Amazon bird detections were sampled across each species classifier-confidence range before biodiversity metrics were derived. In both cases, PAMalytics reduced manual handling and validation time. By turning an ad hoc step into an accessible, structured workflow for conservation practitioners, PAMalytics fills a practical gap in the PAM bioacoustics pipeline and strengthens the link between automated detections and evidence used in biodiversity monitoring and reporting.

ecology↗

bioRxiv2023

Tumor-selective effects of active RAS inhibition in pancreatic ductal adenocarcinoma

Broad-spectrum RAS inhibition holds the potential to benefit roughly a quarter of human cancer patients whose tumors are driven by RAS mutations. However, the impact of inhibiting RAS functions in normal tissues is not known. RMC-7977 is a highly selective inhibitor of the active (GTP-bound) forms of KRAS, HRAS, and NRAS, with affinity for both mutant and wild type (WT) variants. As >90% of human pancreatic ductal adenocarcinoma (PDAC) cases are driven by activating mutations in KRAS, we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models, including human and murine cell lines, human patient-derived organoids, human PDAC explants, subcutaneous and orthotopic cell-line or patient derived xenografts, syngeneic allografts, and genetically engineered mouse models. We observed broad and pronounced anti-tumor activity across these models following direct RAS inhibition at doses and concentrations that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumor versus normal tissues. Treated tumors exhibited waves of apoptosis along with sustained proliferative arrest whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS inhibition in the setting of PDAC.

cancer biology↗

bioRxiv2022

Agonistic anti-CD40 converts Tregs into Type 1 effectors within the tumor micro-environment

Multiple cell types, molecules, and processes contribute to inhibition of anti-tumor effector responses, often frustrating effective immunotherapy. Among these, Foxp3+ CD4+ cells (Tregs) are well-recognized to play an immunosuppressive role in the tumor microenvironment. The first clinically successful checkpoint inhibitor, anti-CTLA-4 antibody, may deplete Tregs at least in part by antibody-dependent cellular cytotoxicity (ADCC), but this effect is unreliable in mice, including in a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC). In contrast, agonistic CD40 antibody, which serves as an effective therapy, is associated with notable Treg disappearance in the PDAC model. The mechanism of CD40-mediated Treg loss is poorly understood, as Tregs are CD40-negative. Here we have explored the mechanistic basis for the loss of Foxp3 T cells upon anti-CD40 treatment and find, using tissue-level multiplex immunostaining and orthogonal dissociated cell analyses, that Tregs are not depleted but converted into interferon-{gamma} (IFN-{gamma}) producing, Type I CD4+ T effector cells. This process depends on IL-12 and IFN-{gamma} signaling evoked by action of the anti-CD40 antibody on dendritic cells (DCs), especially BATF3-dependent cDC1s. These findings provide insight into a previously unappreciated mechanism of CD40 agonism as a potent anti-tumor intervention that promotes the re-programming of Tregs into tumor-reactive CD4+ effector T cells, markedly augmenting the anti-tumor response.

immunology↗