Domain Conditioned Adaptation Network

Tremendous research efforts have been made to thrive deep domain adaptation (DA) by seeking domain-invariant features. Most existing deep DA models only focus on aligning feature representations of task-specific layers across domains while integrating a totally shared convolutional architecture for source and target. However, we argue that such strongly-shared convolutional layers might be harmful for domain-specific feature learning when source and target data distribution differs to a large extent. In this paper, we relax a shared-convnets assumption made by previous DA methods and propose a Domain Conditioned Adaptation Network (DCAN), which aims to excite distinct convolutional channels with a domain conditioned channel attention mechanism. As a result, the critical low-level domain-dependent knowledge could be explored appropriately. As far as we know, this is the first work to explore the domain-wise convolutional channel activation for deep DA networks. Moreover, to effectively align high-level feature distributions across two domains, we further deploy domain conditioned feature correction blocks after task-specific layers, which will explicitly correct the domain discrepancy. Extensive experiments on three cross-domain benchmarks demonstrate the proposed approach outperforms existing methods by a large margin, especially on very tough cross-domain learning tasks.Comment: Accepted by AAAI 202

Autologous cryo-shocked neutrophils enable targeted therapy of sepsis via broad-spectrum neutralization of pro-inflammatory cytokines and endotoxins

Background: Sepsis is a life-threatening disease characterized by multiple organ failure due to excessive activation of the inflammatory response and cytokine storm. Despite recent advances in the clinical use of anti-cytokine biologics, sepsis treatment efficacy and improvements in mortality remain unsatisfactory, largely due to the mechanistic complexity of immune regulation and cytokine interactions.Methods: In this study, a broad-spectrum anti-inflammatory and endotoxin neutralization strategy was developed based on autologous “cryo-shocked” neutrophils (CS-Neus) for the management of sepsis. Neutrophils were frozen to death using a novel liquid nitrogen “cryo-shock” strategy. The CS-Neus retained the source cell membrane structure and functions related to inflammatory site targeting, broad-spectrum inflammatory cytokines, and endotoxin (LPS) neutralizing properties. This strategy aimed to disable harmful pro-inflammatory functions of neutrophils, such as cytokine secretion. Autologous cell-based therapy strategies were employed to avoid immune rejection and enhance treatment safety.Results: In both LPS-induced sepsis mouse models and clinical patient-derived blood samples, CS-Neus treatment significantly ameliorated cytokine storms by removing inflammatory cytokines and endotoxin. The therapy showed notable anti-inflammatory therapeutic effects and improved the survival rate of mice.Discussion: The results of this study demonstrate the potential of autologous “cryo-shocked” neutrophils as a promising therapeutic approach for managing sepsis. By targeting inflammatory organs and exhibiting anti-inflammatory activity, CS-Neus offer a novel strategy to combat the complexities of sepsis treatment. Further research and clinical trials are needed to validate the efficacy and safety of this approach in broader populations and settings

Fully Homomorphic Encryption with k-bit Arithmetic Operations

We present a fully homomorphic encryption scheme continuing the line of works of Ducas and Micciancio (2015, [DM15]), Chillotti et al. (2016, [CGGI16a]; 2017, [CGGI17]; 2018, [CGGI18a]), and Gao (2018,[Gao18]). Ducas and Micciancio (2015) show that homomorphic computation of one bit operation on LWE ciphers can be done in less than a second, which is then reduced by Chillotti et al. (2016, 2017, 2018) to 13ms. According to Chillotti et al. (2018, [CGGI18b]), the cipher expansion for TFHE is still 8000. The ciphertext expansion problem was greatly reduced by Gao (2018) to 6 with private-key encryption and 20 for public key encryption. The bootstrapping in Gao (2018) is only done one bit at a time, and the bootstrapping design matches the previous two works in efficiency. Our contribution is to present a fully homomorphic encryption scheme based on these preceding schemes that generalizes the Gao (2018) scheme to perform operations on k-bit encrypted data and also removes the need for the Independence Heuristic of the Chillotti et al. papers. The amortized cost of computing k-bits at a time improves the efficiency. Operations supported include addition and multiplication modulo $2^k$, addition and multiplication in the integers as well as exponentiation, field inversion and the machine learning activation function RELU. The ciphertext expansion factor is also further improved, for $k = 4$ our scheme achieves a ciphertext expansion factor of 2.5 under secret key and 6.5 under public key. Asymptotically as k increases, our scheme achieves the optimal ciphertext expansion factor of 1 under private key encryption and 2 under public key encryption. We also introduces techniques for reducing the size of the bootstrapping key. Keywords. FHE, lattices, learning with errors (LWE), ring learning with errors (RLWE), TFHE, data security, RELU, machine learnin

Relative Quantification of Protein-Protein Interactions Using a Dual Luciferase Reporter Pull-Down Assay System

The identification and quantitative analysis of protein-protein interactions are essential to the functional characterization of proteins in the post-proteomics era. The methods currently available are generally time-consuming, technically complicated, insensitive and/or semi-quantitative. The lack of simple, sensitive approaches to precisely quantify protein-protein interactions still prevents our understanding of the functions of many proteins. Here, we develop a novel dual luciferase reporter pull-down assay by combining a biotinylated Firefly luciferase pull-down assay with a dual luciferase reporter assay. The biotinylated Firefly luciferase-tagged protein enables rapid and efficient isolation of a putative Renilla luciferase-tagged binding protein from a relatively small amount of sample. Both of these proteins can be quantitatively detected using the dual luciferase reporter assay system. Protein-protein interactions, including Fos-Jun located in the nucleus; MAVS-TRAF3 in cytoplasm; inducible IRF3 dimerization; viral protein-regulated interactions, such as MAVS-MAVS and MAVS-TRAF3; IRF3 dimerization; and protein interaction domain mapping, are studied using this novel assay system. Herein, we demonstrate that this dual luciferase reporter pull-down assay enables the quantification of the relative amounts of interacting proteins that bind to streptavidin-coupled beads for protein purification. This study provides a simple, rapid, sensitive, and efficient approach to identify and quantify relative protein-protein interactions. Importantly, the dual luciferase reporter pull-down method will facilitate the functional determination of proteins

Causal relationship between atrial fibrillation and cognitive impairment: a Mendelian randomization study

Objective·To investigate the causal relationship between atrial fibrillation (AF) and cognitive impairment.Methods·A two-sample Mendelian randomization (TSMR) analysis was used to assess the potential causality of AF on cognitive dysfunction. Single nucleotide polymorphisms (SNPs) strongly associated with AF were extracted as instrumental variables by using a dataset of a large-scale genome-wide association study (GWAS) on AF. The associations of SNPs with Alzheimer′s disease dementia, Parkinson′s disease dementia, vascular dementia, Lewy body dementia, frontotemporal dementia, undefined dementia, and overall cognitive function assessment were extracted separately from publicly available GWAS data on cognitive dysfunction. The inverse variance-weighted (IVW) method was used for the main analysis, and sensitivity analyses were conducted by using Cochran′s Q test, MR-Egger regression, and leave-one-out method. To verify the robustness of the results, replicate analyses and meta-analyses were performed by using different GWAS data.Results·In the initial analysis, 101 SNPs were extracted as instrumental variables from a meta-analysis of a genome-wide association study involving up to 1 030 836 individuals. The IVW analysis showed no evidence for causal associations between AF and dementia [dementia (OR=1.032; 95%CI 0.973‒1.094; P=0.290), Parkinson′s disease dementia (OR=1.004; 95%CI 0.780‒1.291; P=0.977), vascular dementia (OR=1.123; 95%CI 0.969‒1.301; P=0.125), or unspecified dementia (OR=1.013; 95%CI 0.910‒1.129; P=0.807)]. In the replication analysis, 27 SNPs were extracted as instrumental variables from the FinnGen AF GWAS data, and the IVW analysis were consistent with the initial analysis [cognitive function (OR=0.999; 95%CI 0.982‒1.016; P=0.874), Alzheimer′s disease dementia (OR=0.977; 95%CI 0.943‒1.012; P=0.193), Lewy body dementia (OR=1.014; 95%CI 0.898‒1.145; P=0.826), or frontotemporal dementia (OR=0.996; 95%CI 0.745‒1.333; P=0.980)]. Both Mendelian randomization analyses and meta-analyses showed no evidence of an association between genetically predicted AF and different types of dementia or overall cognitive function assessment. MR-Egger regression suggested no horizontal pleiotropy and leave-one-out analysis showed stable results after individually removing each SNP.Conclusion·No evidence of a causal relationship between AF and cognitive impairment was found. The associations observed in observational studies can be partially attributed to confounding factors such as shared biology or co-morbidities

Newcastle Disease Virus V Protein Inhibits Cell Apoptosis and Promotes Viral Replication by Targeting CacyBP/SIP

Newcastle disease virus (NDV) has been classified by the World Organization for Animal Health (OIE) as a notable disease-causing virus, and this virus has the ability to infect a wide range of birds. V protein is a non-structural protein of NDV. V protein has been reported to inhibit cell apoptosis (Park et al., 2003a) and promote viral replication (Huang et al., 2003), however, the mechanisms of action of V protein have not been elucidated. In the present study, a yeast two-hybrid screen was performed, and V protein was found to interact with the CacyBP/SIP protein. The results of co-immunoprecipitation and immuno-colocalization assays confirmed the interaction between V protein and CacyBP/SIP. The results of quantitative-PCR and viral plaque assays showed that overexpression of CacyBP/SIP inhibited viral replication in DF-1 cells. Overexpression of CacyBP/SIP in DF-1 cells induced caspase3-dependent apoptosis. The effect of knocking down CacyBP/SIP by siRNA was the opposite of that observed upon overexpression. Moreover, it is known that NDV induces cell apoptosis via multiple caspase-dependent pathways. Furthermore, V protein inhibited cell apoptosis and downregulated CacyBP/SIP expression in DF-1 cells. Taken together, the findings of the current study indicate that V protein interacts with CacyBP/SIP, thereby regulating cell apoptosis and viral replication