In this paper, we present the Lipschitz regularization theory and algorithms for a novel Loss-Sensitive Generative Adversarial Network (LS-GAN). Specifically, it trains a loss function to distinguish ...between real and fake samples by designated margins, while learning a generator alternately to produce realistic samples by minimizing their losses. The LS-GAN further regularizes its loss function with a Lipschitz regularity condition on the density of real data, yielding a regularized model that can better generalize to produce new data from a reasonable number of training examples than the classic GAN. We will further present a Generalized LS-GAN (GLS-GAN) and show it contains a large family of regularized GAN models, including both LS-GAN and Wasserstein GAN, as its special cases. Compared with the other GAN models, we will conduct experiments to show both LS-GAN and GLS-GAN exhibit competitive ability in generating new images in terms of the Minimum Reconstruction Error (MRE) assessed on a separate test set. We further extend the LS-GAN to a conditional form for supervised and semi-supervised learning problems, and demonstrate its outstanding performance on image classification tasks.
This paper presents a new technique for artificial neural network (ANN) inverse modeling and applications to microwave filters. In inverse modeling of a microwave component, the inputs to the model ...are electrical parameters such as <inline-formula> <tex-math notation="LaTeX">S </tex-math></inline-formula>-parameters, and the outputs of the model are geometrical or physical parameters. Since the analytical formula of the inverse input-output relationship does not exist, the ANN becomes a logical choice, because it can be trained to learn from the data in inverse modeling. The main challenge of inverse modeling is the nonuniqueness problem. This problem in the ANN inverse modeling is that different training samples with the same or very similar input values have quite different (contradictory) output values (multivalued solutions). In this paper, we propose a multivalued neural network inverse modeling technique to associate a single set of electrical parameters with multiple sets of geometrical or physical parameters. One set of geometrical or physical parameters is called one value of our proposed inverse model. Our proposed multivalued neural network is structured to accommodate multiple values for the model output. We also propose a new training error function to focus on matching each training sample using only one value of our proposed inverse model, while other values are free and can be trained to match other contradictory samples. In this way, our proposed multivalued neural network can learn all the training data by automatically redirecting contradictory information into different values of the proposed inverse model. Therefore, our proposed technique can solve the nonuniqueness problem in a simpler and more automated way compared with the existing ANN inverse modeling techniques. This technique is illustrated by inverse modeling and parameter extraction of four microwave filter examples.
Atroposelective synthesis of axially chiral biaryls by palladium‐catalyzed C−H olefination, using tert‐leucine as an inexpensive, catalytic, and transient chiral auxiliary, has been realized. This ...strategy provides a highly efficient and straightforward access to a broad range of enantioenriched biaryls in good yields (up to 98 %) with excellent enantioselectivities (95 to >99 % ee). Kinetic resolution of trisubstituted biaryls bearing sterically more demanding substituents is also operative, thus furnishing the optically active olefinated products with excellent selectivity (95 to >99 % ee, s‐factor up to 600).
No attachements: The title reaction employs tert‐leucine as a transient chiral auxiliary and provides efficient access to enantioenriched biaryls in good yields (up to 98 %) with excellent enantioselectivities (up to >99 % ee). Kinetic resolution of trisubstituted biaryls bearing sterically more demanding substituents is also operative, thus furnishing the optically active olefinated products with excellent selectivity (up to >99 % ee, s‐factor up to 600).
The sirtuin family in health and disease Wu, Qi-Jun; Zhang, Tie-Ning; Chen, Huan-Huan ...
Signal transduction and targeted therapy,
12/2022, Volume:
7, Issue:
1
Journal Article
Peer reviewed
Open access
Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological ...processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.
The nutrients-rich food (NRF) index provides a score of diet quality. Although high diet quality is associated with survival of ovarian cancer (OC), the associations between NRF index scores and OC ...survival remain unevaluated.
The prospective cohort study enrolled 703 women with newly diagnosed epithelial OC to assess the correlations between NRF index scores and overall survival (OS) in OC patients. Dietary consumption was evaluated through a food frequency questionnaire and diet quality was calculated based on NRF index scores, including three limited nutrients and six (NRF6.3), nine (NRF9.3), or eleven (NRF11.3) benefit nutrients. All-cause deaths were ascertained through medical records combined with active follow-up. Immunohistochemistry (IHC) analyses were conducted to evaluate the expression of IHC indicators (including Estrogen Receptor, Progesterone Receptor, p53, Vimentin, and Wilms' tumor 1), which were identified by two independent pathologists. The Cox proportional hazards regression models were applied for estimating the hazard ratios (HRs) and 95% confidence intervals (CIs). Moreover, we performed the penalized cubic splines model to assess the curvilinear associations of NRF index scores with OC survival.
During the median follow-up of 37.17 (interquartile: 24.73-50.17) months, 130 deaths were documented. Compared to the lowest tertiles, the highest tertile of index scores NRF9.3 (HR = 0.63, 95% CI = 0.41-0.95), NRF6.3 (HR = 0.59, 95% CI = 0.39-0.89), and NRF11.3 (HR = 0.57, 95% CI = 0.38-0.87) were correlated to better OS, showing an obvious linear trend (all
trend < 0.05). Interestingly, the curvilinear association between the NRF6.3 index score and OC survival was also observed (
non-linear < 0.05). Subgroup analyses, stratified by clinical, demographic, and IHC features, showed similar risk associations as the unstratified results. Furthermore, there were significant multiplicative interactions between NRF index scores and Progestogen Receptors as well as Wilms' tumor 1 expressions (all
interaction < 0.05).
Higher NRF index scores were associated with an improved OS in OC patients.
Summary
Using genetic resistance against bacterial blight (BB) caused by Xanthomonas oryzae pathovar oryzae (Xoo) is a major objective in rice breeding programmes. Prime editing (PE) has the ...potential to create novel germplasm against Xoo. Here, we use an improved prime‐editing system to implement two new strategies for BB resistance. Knock‐in of TAL effector binding elements (EBE) derived from the BB susceptible gene SWEET14 into the promoter of a dysfunctional executor R gene xa23 reaches 47.2% with desired edits including biallelic editing at 18% in T0 generation that enables an inducible TALE‐dependent BB resistance. Editing the transcription factor TFIIA gene TFIIAγ5 required for TAL effector‐dependent BB susceptibility recapitulates the resistance of xa5 at an editing efficiency of 88.5% with biallelic editing rate of 30% in T0 generation. The engineered loci provided resistance against multiple Xoo strains in T1 generation. Whole‐genome sequencing detected no OsMLH1dn‐associated random mutations and no off‐target editing demonstrating high specificity of this PE system. This is the first‐ever report to use PE system to engineer resistance against biotic stress and to demonstrate knock‐in of 30‐nucleotides cis‐regulatory element at high efficiency. The new strategies hold promises to fend rice off the evolving Xoo strains and protect it from epidemics.
Axially chiral arylpyrroles are key components of pharmaceuticals and natural products as well as chiral catalysts and ligands for asymmetric transformations. However, the catalytic enantioselective ...construction of optically active arylpyrroles remains a formidable challenge. Here we disclose a highly efficient strategy to access enantioenriched axially chiral arylpyrroles by means of organocatalytic atroposelective desymmetrization and kinetic resolution. Depending on the remote control of chiral catalyst, the arylpyrroles were obtained in high yields and excellent enantioselectivities under mild reaction conditions. This strategy tolerates a wide range of functional groups, providing a facile avenue to approach axially chiral arylpyrroles from simple and readily available starting materials. Selected arylpyrrole products proved to be efficient chiral ligands in asymmetric catalysis and also important precursors for further synthetic transformations into highly functionalized pyrroles with potential bioactivity, especially the axially chiral fully substituted arylpyrroles.
The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C−H activation. Herein, we ...reported the synthesis of axially chiral biaryls by Pd‐catalyzed atroposelective C−H olefination. A novel chiral spiro phosphoric acid, STRIP, was identified as a superior ligand for this transformation. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee). Density functional theory was used to gain a theoretical understanding of the enantioselectivities in this reaction.
The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C−H activation. Herein, the synthesis of axially chiral biaryls by Pd‐catalyzed atroposelective C−H olefination is reported. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee).
The atroposelective synthesis of axially chiral styrenes remains a formidable challenge due to their relatively lower rotational barriers compared to the biaryl atropoisomers. Herein, we describe the ...construction of axially chiral styrenes through PdII‐catalyzed atroposelective C−H olefination, using a bulky amino amide as a transient chiral auxiliary. Various axially chiral styrenes were produced with good yields and high enantioselectivity (up to 95 % yield and 99 % ee). Carboxylic acid derivatives of the resulting axially chiral styrenes showed superior enantiocontrol over the biaryl counterparts in CoIII‐catalyzed enantioselective C(sp3)−H amidation of thioamide. Mechanistic studies suggest that C−H cleavage is the enantioselectivity‐determining step.
Axially chiral styrenes were constructed through a PdII‐catalyzed atroposelective C−H olefination with a bulky amino amide as a transient chiral auxiliary. Various axially chiral styrenes were produced with good yields and high enantioselectivity. Carboxylic acid derivatives of these axially chiral styrenes showed superior enantiocontrol compared to the biaryl counterparts in CoIII‐catalyzed enantioselective C(sp3)−H amidation of ferrocenes.
Deep neural networks have been successfully applied to many real-world applications. However, such successes rely heavily on large amounts of labeled data that is expensive to obtain. Recently, many ...methods for semi-supervised learning have been proposed and achieved excellent performance. In this study, we propose a new EnAET framework to further improve existing semi-supervised methods with self-supervised information. To our best knowledge, all current semi-supervised methods improve performance with prediction consistency and confidence ideas. We are the first to explore the role of self-supervised representations in semi-supervised learning under a rich family of transformations. Consequently, our framework can integrate the self-supervised information as a regularization term to further improve all current semi-supervised methods. In the experiments, we use MixMatch, which is the current state-of-the-art method on semi-supervised learning, as a baseline to test the proposed EnAET framework. Across different datasets, we adopt the same hyper-parameters, which greatly improves the generalization ability of the EnAET framework. Experiment results on different datasets demonstrate that the proposed EnAET framework greatly improves the performance of current semi-supervised algorithms. Moreover, this framework can also improve supervised learning by a large margin, including the extremely challenging scenarios with only 10 images per class. The code and experiment records are available in https://github.com/maple-research-lab/EnAET .
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