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1.
IEEE Trans Pattern Anal Mach Intell ; 46(6): 4075-4089, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38194378

RESUMO

We present incomplete gamma kernels, a generalization of Locally Optimal Projection (LOP) operators. In particular, we reveal the relation of the classical localized L1 estimator, used in the LOP operator for point cloud denoising, to the common Mean Shift framework via a novel kernel. Furthermore, we generalize this result to a whole family of kernels that are built upon the incomplete gamma function and each represents a localized Lp estimator. By deriving various properties of the kernel family concerning distributional, Mean Shift induced, and other aspects such as strict positive definiteness, we obtain a deeper understanding of the operator's projection behavior. From these theoretical insights, we illustrate several applications ranging from an improved Weighted LOP (WLOP) density weighting scheme and a more accurate Continuous LOP (CLOP) kernel approximation to the definition of a novel set of robust loss functions. These incomplete gamma losses include the Gaussian and LOP loss as special cases and can be applied to various tasks including normal filtering. Furthermore, we show that the novel kernels can be included as priors into neural networks. We demonstrate the effects of each application in a range of quantitative and qualitative experiments that highlight the benefits induced by our modifications.

2.
Cells ; 13(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38994969

RESUMO

During infection, adenoviruses inhibit the cellular RNA interference (RNAi) machinery by saturating the RNA-induced silencing complex (RISC) of the host cells with large amounts of virus-derived microRNAs (mivaRNAs) that bind to the key component of the complex, Argonaute 2 (AGO2). In the present study, we investigated AGO2 as a prominent player at the intersection between human adenovirus 5 (HAdV-5) and host cells because of its ability to interfere with the HAdV-5 life cycle. First, the ectopic expression of AGO2 had a detrimental effect on the ability of the virus to replicate. In addition, in silico and in vitro analyses suggested that endogenous microRNAs (miRNAs), particularly hsa-miR-7-5p, have similar effects. This miRNA was found to be able to target the HAdV-5 DNA polymerase mRNA. The inhibitory effect became more pronounced upon overexpression of AGO2, likely due to elevated AGO2 levels, which abolished the competition between cellular miRNAs and mivaRNAs for RISC incorporation. Collectively, our data suggest that endogenous miRNAs would be capable of significantly inhibiting viral replication if adenoviruses had not developed a mechanism to counteract this function. Eventually, AGO2 overexpression-mediated relief of the RISC-saturating action of mivaRNAs strongly enhanced the effectiveness of artificial miRNAs (amiRNAs) directed against the HAdV-5 preterminal protein (pTP) mRNA, suggesting a substantial benefit of co-expressing amiRNAs and AGO2 in RNAi-based strategies for the therapeutic inhibition of adenoviruses.


Assuntos
Adenovírus Humanos , Proteínas Argonautas , MicroRNAs , Replicação Viral , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Adenovírus Humanos/genética , Adenovírus Humanos/fisiologia , Complexo de Inativação Induzido por RNA/metabolismo , Complexo de Inativação Induzido por RNA/genética , Interferência de RNA , Células HEK293
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