A squared smoothing Newton method for nonsmooth matrix equations and its applications in semidefinite optimization problems

10.1137/S1052623400379620SIAM Journal on Optimization143783-80

From development to diseases: The role of 5hmC in brain

AbstractEpigenetic modulations play essential roles in diverse biological processes. During the past several years, DNA demethylation has been discovered in embryonic and postnatal development. Although some potential functions of DNA methylation have been demonstrated already, many questions remain in terms of unveiling the role of 5hmC; whether it serves either merely as an intermediate of DNA demethylation or as a stable epigenetic marker. 5-hydroxymethylcytosine (5hmC) is proved to be not merely serving as an intermediate of DNA demethylation, but also acts as a stable epigenetic marker. This review summarizes the current knowledge of the function of 5hmC in brain with the focus on the neuronal activity, neurodevelopment, aging, and neurological diseases

Metasurface array for single-shot spectroscopic ellipsometry

Spectroscopic ellipsometry is a potent method that is widely adopted for the measurement of thin film thickness and refractive index. However, a conventional ellipsometer, which utilizes a mechanically rotating polarizer and grating-based spectrometer for spectropolarimetric detection, is bulky, complex, and does not allow real-time measurements. Here, we demonstrated a compact metasurface array-based spectroscopic ellipsometry system that allows single-shot spectropolarimetric detection and accurate determination of thin film properties without any mechanical movement. The silicon-based metasurface array with a highly anisotropic and diverse spectral response is combined with iterative optimization to reconstruct the full Stokes polarization spectrum of the light reflected by the thin film with high fidelity. Subsequently, the film thickness and refractive index can be determined by fitting the measurement results to a proper material model with high accuracy. Our approach opens up a new pathway towards a compact and robust spectroscopic ellipsometry system for the high throughput measurement of thin film properties

Metamorphic relations for enhancing system understanding and use

Modern information technology paradigms, such as online services and off-the-shelf products, often involve a wide variety of users with different or even conflicting objectives. Every software output may satisfy some users, but may also fail to satisfy others. Furthermore, users often do not know the internal working mechanisms of the systems. This situation is quite different from bespoke software, where developers and users usually know each other. This paper proposes an approach to help users to better understand the software that they use, and thereby more easily achieve their objectives—even when they do not fully understand how the system is implemented. Our approach borrows the concept of metamorphic relations from the field of metamorphic testing (MT), using it in an innovative way that extends beyond MT. We also propose a "symmetry" metamorphic relation pattern and a "change direction" metamorphic relation input pattern that can be used to derive multiple concrete metamorphic relations. Empirical studies reveal previously unknown failures in some of the most popular applications in the world, and show how our approach can help users to better understand and better use the systems. The empirical results provide strong evidence of the simplicity, applicability, and effectiveness of our methodology

Microbiota comparison of amur ide (Leuciscus waleckii) intestine and waters at alkaline water and freshwater as the living environment

The intestinal microbiota of marine animals was influenced by the water and environment in which they live. The Amur ide (Leuciscus waleckii) adapts to extremely high alkalinity and is an ideal material for aquacultural studies of alkaline adaptation. In this study, we screened intestinal indicator flora and functional redundancy of intestinal colonies in alkaline-water species (AW) and freshwater species (FW) of Amur ide (L. waleckii) in these different aquatic environments. The available vs. community composition correlations were then predicted by contrasting each other with the flora contained in environmental water samples. Here, five microbial species and six genera were identified owing to the classifiable sequence. The intestinal microbiota that existed in AW and FW had approximately 1/3 of the operational taxonomic units in the respective living water environments, meaning gut microbes in the aqueous habitats will have an influential association with gut microbes in AW and FW. Compared to the bacterial composition of the FW intestine and that present in freshwater, Moraxella osloensis, Psychrobacter maritimus, and Psychrobacter faecalis were significantly enriched in the intestine of AW and alkaline water samples. In the FW intestine and freshwater samples, however, Cryptomonas curvata and Polynucleobacter asymbioticus were highly improved, which can be summarized as Enterobacter sp., the predominant population in the AW gut, while Aeromonas and Ralstonia being primarily present in FW intestines. Photosynthetic bacteria were most significant in both water samples. The results indicated that the intestinal microbiota composition, abundance, and diversity of AW and FW were quite different. In contrast, the microbial composition of the additional alkaline water and freshwater environments showed slight differences. This study expects to enhance our understanding of the alkalinity tolerance of L. waleckii, which will be provided for the breeding of fish living in alkaline water, and push the development of alkaline water resources with increased efficiency.info:eu-repo/semantics/publishedVersio

Rutin Protects against Pirarubicin-Induced Cardiotoxicity through TGF- β

We investigated the potential protective effect of rutinum (RUT) against pirarubicin- (THP-) induced cardiotoxicity. THP was used to induce toxicity in rat H9c2 cardiomyoblasts. Positive control cells were pretreated with a cardioprotective agent dexrazoxane (DZR) prior to treatment with THP. Some of the cells were preincubated with RUT and a p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, both individually and in combination, prior to THP exposure. At a dose range of 30–70 μM, RUT significantly prevented THP-induced reduction in cell viability; the best cardioprotective effect was observed at a dose of 50 μM. Administration of RUT and SB203580, both individually as well as in combination, suppressed the elevation of intracellular ROS, inhibited cell apoptosis, and reversed the THP-induced upregulation of TGF-β1, p-p38 MAPK, cleaved Caspase-9, Caspase-7, and Caspase-3. A synergistic effect was observed on coadministration of RUT and SB203580. RUT protected against THP-induced cardiotoxicity by inhibition of ROS generation and suppression of cell apoptosis. The cardioprotective effect of RUT appears to be associated with the modulation of the TGF-β1-p38 MAPK signaling pathway

Phospho-aspirin (MDC-22) inhibits breast cancer in preclinical animal models: an effect mediated by EGFR inhibition, p53 acetylation and oxidative stress

BACKGROUND: The anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we synthesized phospho-aspirin (PA-2; MDC-22), a novel derivative of aspirin, and evaluated its chemotherapeutic and chemopreventive efficacy in preclinical models of triple negative breast cancer (TNBC). METHODS: Efficacy of PA-2 was evaluated in human breast cancer cells in vitro, and in orthotopic and subcutaneous TNBC xenografts in nude mice. Mechanistic studies were also carried out to elucidate the mechanism of action of PA-2. RESULTS: PA-2 inhibited the growth of TNBC cells in vitro more potently than aspirin. Treatment of established subcutaneous TNBC xenografts (MDA-MB-231 and BT-20) with PA-2 induced a strong growth inhibitory effect, resulting in tumor stasis (79% and 90% inhibition, respectively). PA-2, but not aspirin, significantly prevented the development of orthotopic MDA-MB-231 xenografts (62% inhibition). Mechanistically, PA-2: 1) inhibited the activation of epidermal growth factor receptor (EGFR) and suppressed its downstream signaling cascades, including PI3K/AKT/mTOR and STAT3; 2) induced acetylation of p53 at multiple lysine residues and enhanced its DNA binding activity, leading to cell cycle arrest; and 3) induced oxidative stress by suppressing the thioredoxin system, consequently inhibiting the activation of the redox sensitive transcription factor NF-κB. These molecular alterations were observed in vitro and in vivo, demonstrating their relevance to the anticancer effect of PA-2. CONCLUSIONS: Our findings demonstrate that PA-2 possesses potent chemotherapeutic efficacy against TNBC, and is also effective in its chemoprevention, warranting further evaluation as an anticancer agent