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Sung, B.

Publications and source records attributed to Sung, B..

2 recordsLinked to original sources

Few-Shot Classification of Cryo-EM Micrographs Using Triplet Loss Embeddings

Micrograph quality assessment in cryo-electron microscopy (cryo-EM) presents a significant challenge: users must either manually screen thousands of micrographs or expend substantial computational resources processing potentially low-quality data. While few-shot learning has been applied to particle picking and subtomogram classification in cryo-EM, its application to micrograph-level quality assessment remains largely unexplored. We present a framework combining few-shot learning with cryo-EM micrograph classification using triplet loss embeddings. By combining real-space and Fourier-space information in an embedding network trained with triplet loss, we achieve competitive performance across multiple EMPIAR datasets using as few as 1-5 labeled examples per class. Our approach demonstrates improvements over traditional cross-entropy training, which often collapses to predicting only the majority class in the few-shot regime. These results suggest a practical framework for rapid adaptation of automated micrograph screening to new experimental conditions with minimal manual labeling.

biophysics↗

A brain-shuttled antibody targeting alpha synuclein aggregates for the treatment of synucleinopathies

Parkinsons disease and multiple system atrophy are members of a class of devastating neurodegenerative diseases called synucleinopathies, which are characterized by the presence of alpha-synuclein (-Syn) rich aggregates in the brains of patients. Passive immunotherapy targeting these aggregates is an attractive disease-modifying strategy. Such an approach must not only demonstrate target selectivity towards -Syn aggregates, but also achieve appropriate brain exposure to have the desired therapeutic effect. Here we present preclinical data for a next-generation antibody for the treatment of synucleinopathies. SAR446159 (ABL301) is a bispecific antibody composed of an -Syn-binding immunoglobulin (IgG) and an engineered insulin-like growth factor receptor 1 (IGF1R) binding single-chain variable fragment (scFv), acting as a shuttle to transport an antibody across the blood-brain barrier (BBB). SAR446159 binds tightly and preferentially to -Syn aggregates and prevents their seeding capacity in vitro and in vivo. Incubation with SAR446159 reduced -Syn preformed fibrils (PFFs) uptake in neurons and facilitated uptake and clearance by microglia. In wild type mice injected in the striatum with -Syn PFFs, treatment with SAR446159 reduced the spread of aSyn pathology as measured by phosphorylated -Syn staining and lessened the severity of motor phenotypes. Additionally, in 9-month-old transgenic mice overexpressing -Syn (mThy1--Syn, Line 61), repeated treatment with SAR446159 reduced markers of -Syn aggregation in the brain. SAR446159 had significantly higher brain and CSF penetration over a sustained period than its monospecific counterpart (1E4) in rats and monkeys. The binding properties of SAR446159 combined with its brain-shuttle technology make it a potent, next-generation immunotherapeutic for treating synucleinopathies.

neuroscience↗