Torus knots in Lens spaces, open Gromov-Witten invariants, and topological recursion

Starting from a torus knot $\mathcal{K}$ in the lens space $L(p,-1)$, we construct a Lagrangian sub-manifold $L_{\mathcal{K}}$ in $\mathcal{X}=\big(\mathcal{O}_{\mathbb{P}^1}(-1)\oplus \mathcal{O}_{\mathbb{P}^1}(-1)\big)/\mathbb{Z}_p$ under the conifold transition. We prove a mirror theorem which relates the all genus open-closed Gromov-Witten invariants of $(\mathcal{X},L_{\mathcal{K}})$ to the topological recursion on the B-model spectral curve. This verifies a conjecture in \cite{Bor-Bri} in the case of lens space.Comment: 43 pages, 6 figure

Selective Inhibition of Cysteine-Dependent Enzymes by Bioorthogonal Tethering

A general approach for the rapid and selective inhibition of enzymes in cells using a common tool compound would be of great value for research and therapeutic development. We previously reported a chemogenetic strategy that addresses this challenge for kinases, relying on bioorthogonal tethering of a pan inhibitor to a target kinase through a genetically encoded non-canonical amino acid. However, pan inhibitors are not available for many enzyme classes. Here, we expand the scope of the chemogenetic strategy to cysteine-dependent enzymes by bioorthogonal tethering of electrophilic warheads. For proof of concept, selective inhibition of two E2 ubiquitin-conjugating enzymes, UBE2L3 and UBE2D1, was demonstrated in biochemical assays. Further development and optimization of this approach should enable its use in cells as well as other cysteine-dependent enzymes, facilitating the investigation of their cellular function and validation as therapeutic targets

Structural and functional connectivity between the lateral posterior-pulvinar complex and primary visual cortex in the ferret

The role of higher-order thalamic structures in sensory processing remains poorly understood. Here, we used the ferret (Mustela putorius furo) as a novel model species for the study of the lateral posterior-pulvinar complex (LP/pulvinar) and its structural and functional connectivity with area 17 (primary visual cortex, V1). We found reciprocal anatomical connections between the lateral part of the Lateral Posterior Nucleus of the LP/pulvinar (LPl) and V1. In order to investigate the role of this feedback loop between LPl and V1 in shaping network activity, we determined the functional interactions between LPl and supragranular, granular, and infragranular layers of V1 by recording multiunit activity (MUA) and local field potential (LFP). Coherence was strongest between LPl and supragranular V1 with the most distinct peaks in the delta and alpha frequency bands. Inter-area interaction measured by spike-phase coupling identified the delta frequency band dominated by infragranular V1 and multiple frequency bands that were most pronounced in supragranular V1. This inter-area coupling was differentially modulated by full-field synthetic and naturalistic visual stimulation. We also found that visual responses in LPl were distinct from the ones in V1 in terms of their reliability. Together, our data support a model of multiple communication channels between the LPl and layers of V1 that are enabled by oscillations in different frequency bands. This demonstration of anatomical and functional connectivity between LPl and V1 in ferrets provides a roadmap for studying the interaction dynamics during behavior and a template for identifying activity dynamics of other thalamic feedback loops

Development and validation of novel immune-inflammation-based clinical predictive nomograms in HER2-negative advanced gastric cancer

PurposeTo explore the predictive value of multiple immune-inflammatory biomarkers including serum VEGFA and systemic immune-inflammation index (SII) in HER2-negative advanced gastric cancer (AGC) and establish nomograms for predicting the first-line chemotherapeutic efficacy, progression-free survival (PFS) and overall survival (OS) of patients with this fatal disease.MethodsFrom November 2017 to April 2022, 102 and 34 patients with a diagnosis of HER2-negative AGC at the First Affiliated Hospital of Bengbu Medical College were enrolled as development and validation cohorts, respectively. Univariate and multivariate analyses were performed to evaluate the clinical value of the candidate indicators. The variables were screened using LASSO regression analysis. Predictive models were developed using significant predictors and are displayed as nomograms.ResultsBaseline VEGFA expression was significantly higher in HER2-negative AGC patients than in nonneoplastic patients and was associated with malignant serous effusion and therapeutic efficacy (all p<0.001). Multivariate analysis indicated that VEGFA was an independent predictor for first-line therapeutic efficacy and PFS (both p<0.01) and SII was an independent predictor for first-line PFS and OS (both p<0.05) in HER2-negative AGC patients. The therapeutic efficacy model had an R2 of 0.37, a Brier score of 0.15, and a Harrell’s C-index of 0.82 in the development cohort and 0.90 in the validation cohort. The decision curve analysis indicated that the model added more net benefits than VEGFA assessment alone. The PFS/OS models had Harrell’s C-indexes of 0.71/0.69 in the development cohort and 0.71/0.62 in the validation cohort.ConclusionThe established nomograms integrating serum VEGFA/SII and commonly available baseline characteristics provided satisfactory performance in predicting the therapeutic efficacy and prognosis of HER2-negative AGC patients

Spatial-temporal variations of short-lived mesoscale eddies and their environmental effects

Mesoscale eddies (MEs) affect the transport and redistribution of oceanic matter and energy. The long-lived and long-distance propagation of individual eddies has garnered extensive attention; however, short-lived MEs (< 7 days) have been widely overlooked. In this study, the basic features of short-lived MEs and their spatial-temporal variations in a tropical eddy-rich region were extracted and analyzed for the first time. Short-lived cyclonic and anticyclonic eddies (CEs/AEs) were found to be widespread in two eddy belts in the tropical region of the western Pacific warm pool (WPWP). The CEs and AEs were formed by the shear instability between large-scale circulations and were distributed on both sides of the North Equatorial Countercurrent, with significant differences in spatial distribution. The variations in sea surface temperature, mixed layer depth, and surface chlorophyll-a concentration in the core of the WPWP were spatially and temporally related to the development of the two eddy belts. This new insight into short-lived MEs in the tropical region contributes to our current understanding of ocean eddies. The potential impacts of short-lived MEs on climate change, global air–sea interactions, and tropical cyclone formation should receive adequate attention and further assessment in future research