22 research outputs found
SubTuning: Efficient Finetuning for Multi-Task Learning
Finetuning a pretrained model has become a standard approach for training
neural networks on novel tasks, resulting in fast convergence and improved
performance. In this work, we study an alternative finetuning method, where
instead of finetuning all the weights of the network, we only train a carefully
chosen subset of layers, keeping the rest of the weights frozen at their
initial (pretrained) values. We demonstrate that \emph{subset finetuning} (or
SubTuning) often achieves accuracy comparable to full finetuning of the model,
and even surpasses the performance of full finetuning when training data is
scarce. Therefore, SubTuning allows deploying new tasks at minimal
computational cost, while enjoying the benefits of finetuning the entire model.
This yields a simple and effective method for multi-task learning, where
different tasks do not interfere with one another, and yet share most of the
resources at inference time. We demonstrate the efficiency of SubTuning across
multiple tasks, using different network architectures and pretraining methods
Novel Phage Display-Derived Anti-Abrin Antibodies Confer Post-Exposure Protection against Abrin Intoxication
Abrin toxin is a type 2 ribosome inactivating glycoprotein isolated from the seeds of Abrus precatorius (jequirity pea). Owing to its high toxicity, relative ease of purification and accessibility, it is considered a biological threat agent. To date, there is no effective post-exposure treatment for abrin poisoning and passive immunization remains the most effective therapy. However, the effectiveness of anti-abrin monoclonal antibodies for post-exposure therapy following abrin intoxication has not been demonstrated. The aim of this study was to isolate high affinity anti-abrin antibodies that possess potent toxin-neutralization capabilities. An immune scFv phage-display library was constructed from an abrin-immunized rabbit and a panel of antibodies (six directed against the A subunit of abrin and four against the B subunit) was isolated and expressed as scFv-Fc antibodies. By pair-wise analysis, we found that these antibodies target five distinct epitopes on the surface of abrin and that antibodies against all these sites can bind the toxin simultaneously. Several of these antibodies (namely, RB9, RB10, RB28 and RB30) conferred high protection against pulmonary intoxication of mice, when administered six hours post exposure to a lethal dose of abrin. The data presented in this study demonstrate for the first time the efficacy of monoclonal antibodies in treatment of mice after pulmonary intoxication with abrin and promote the use of these antibodies, one or several, for post-exposure treatment of abrin intoxication
Diverse Profiles of Ricin-Cell Interactions in the Lung Following Intranasal Exposure to Ricin
Ricin, a plant-derived exotoxin, inhibits protein synthesis by ribosomal inactivation. Due to its wide availability and ease of preparation, ricin is considered a biothreat, foremost by respiratory exposure. We examined the in vivo interactions between ricin and cells of the lungs in mice intranasally exposed to the toxin and revealed multi-phasic cell-type-dependent binding profiles. While macrophages (MΦs) and dendritic cells (DCs) displayed biphasic binding to ricin, monophasic binding patterns were observed for other cell types; epithelial cells displayed early binding, while B cells and endothelial cells bound toxin late after intoxication. Neutrophils, which were massively recruited to the intoxicated lung, were refractive to toxin binding. Although epithelial cells bound ricin as early as MΦs and DCs, their rates of elimination differed considerably; a reduction in epithelial cell counts occurred late after intoxication and was restricted to alveolar type II cells only. The differential binding and cell-elimination patterns observed may stem from dissimilar accessibility of the toxin to different cells in the lung and may also reflect unequal interactions of the toxin with different cell-surface receptors. The multifaceted interactions observed in this study between ricin and the various cells of the target organ should be considered in the future development of efficient post-exposure countermeasures against ricin intoxication
Cemiplimab as First Line Therapy in Advanced Penile Squamous Cell Carcinoma: A Real-World Experience
In the treatment of cancer, immune checkpoint inhibitors (ICIs) have demonstrated significantly greater effectiveness compared to conventional cytotoxic or platinum-based chemotherapies. To assess the efficacy of ICI’s in penile squamous cell carcinoma (pSCC) we performed a retrospective observational study. We reviewed electronic medical records of patients with penile squamous cell carcinoma (SCC), diagnosed between January 2020 and February 2023. Nine patients were screened, of whom three were ineligible for chemotherapy and received immunotherapy, cemiplimab, in a first-line setting. Each of the three immunotherapy-treated patients achieved almost a complete response (CR) after only a few cycles of therapy. The first patient had cerebral arteritis during treatment and received a high-dose steroid treatment with resolution of the symptoms of arteritis. After tapering down the steroids dose, the patient continued cemiplimab without further toxicity. The other two patients did not have any toxic side effects of the treatment. To the best of our knowledge, this is the first real world report of near CR with cemiplimab as a first-line treatment in penile SCC
Biodiversity data requirements for systematic conservation planning in the Mediterranean Sea
The Mediterranean Sea's biodiversity and ecosystems face many threats due to anthropogenic pressures. Some of these include human population growth, coastal urbanization, accelerated human activities, and climate change. To enhance the formation of a science-based system of marine protected areas in the Mediterranean Sea, data on the spatial distribution of ecological features (abiotic variables, species, communities, habitats, and ecosystems) is required to inform conservation scientists and planners. However, the spatial data required is often lacking. In this review, we aimed to address the status of our knowledge for 3 major types of spatial information: bathymetry, classification of marine habitats, and species distributions. To exemplify the data gaps and approaches to bridge them, we examined case studies that systematically prioritize conservation in the Mediterranean Sea. We found that at present the data required for conservation planning is generally more readily available and of better quality for the European countries located in the Western Mediterranean Sea. Additionally, the Mediterranean Sea is lagging behind other marine regions where rigorous criteria for conservation planning has been applied in the past 20 yr. Therefore, we call upon scientists, governments, and international governmental and non-governmental organizations to harmonize current approaches in marine mapping and to develop a framework that is applicable throughout the Mediterranean region. Such coordination between stakeholders is urgently needed before more countries undertake further extensive habitat mapping, so that future conservation planning can use integrated spatial datasets