Rate of Convergence in Periodic Homogenization for Convex Hamilton-Jacobi Equations with Multiscales

We study the rate of convergence in periodic homogenization for convex Hamilton--Jacobi equations with multiscales, where the Hamiltonian $H=H(x, y, p): \mathbb{R}^n \times \mathbb{T}^n \times \mathbb{R}^n \to \mathbb{R }$ depends on both of the spatial variable and the oscillatory variable. In particular, we show that for Cauchy problem, the rate of convergence is $O(\sqrt{\epsilon})$ by optimal control formulas, scale separations and curve cutting techniques. Additionally, we provide examples that illustrate this rate of convergence is optimal

Case report:TP53 and RB1 loss may facilitate the transformation from lung adenocarcinoma to small cell lung cancer by expressing neuroendocrine markers

INTRODUCTION: Transformation from lung adenocarcinoma (LUAD) to small cell lung cancer (SCLC) is one of the mechanisms responsible for acquired EGFR-TKIs resistance. Although it rarely happens this event determines a rapid disease deterioration and needs specific treatment. PATIENT AND METHOD: We report a case of 75-year-old LUAD female with a p.L858R mutation in Epidermal Growth Factor Receptor (EGFR) who presented with SCLC transformation after responding to first line osimertinib treatment for only 6 months. To understand the underlying molecular mechanism, we retrospectively sequenced the first (LUAD) and the second (SCLC) biopsy using a 56 multi-gene panel. Immunohistochemistry (IHC) staining and Fluorescence In Situ Hybridization (FISH) was applied to confirm the genetic aberrations identified. RESULTS: EGFR p.E709A and p.L858R, Tumor Protein p53 (TP53) p.A159D and Retinoblastoma 1 (RB1) c.365-1G>A were detected in both the diagnostic LUAD and transformed SCLC samples. A high copy number gain for Proto-Oncogene C-Myc (MYC) and a Phosphoinositide 3-Kinase Alpha (PIK3CA) p.E545K mutation were found in the transformed sample specifically. Strong TP53 staining and negative RB1 staining were observed in both LUAD and SCLC samples, but FISH only identified MYC amplification in SCLC tissue. CONCLUSION: We consider the combined presence of MYC amplification with mutations in TP53 and RB1 as drivers of SCLC transformation. Our results highlight the need to systematically evaluate TP53 and RB1 status in LUAD patients to offer a different therapeutic strategy

The Manchurian Walnut Genome: Insights into Juglone and Lipid Biosynthesis

Background Manchurian walnut (Juglans mandshurica Maxim.) is a tree with multiple industrial uses and medicinal properties in the Juglandaceae family (walnuts and hickories). J. mandshurica produces juglone, which is a toxic allelopathic agent and has potential utilization value. Furthermore, the seed of J. mandshurica is rich in various unsaturated fatty acids and has high nutritive value. Findings Here, we present a high-quality chromosome-scale reference genome assembly and annotation for J. mandshurica (n = 16) with a contig N50 of 21.4 Mb by combining PacBio high-fidelity reads with high-throughput chromosome conformation capture data. The assembled genome has an estimated sequence size of 548.7 Mb and consists of 657 contigs, 623 scaffolds, and 40,453 protein-coding genes. In total, 60.99% of the assembled genome consists of repetitive sequences. Sixteen super-scaffolds corresponding to the 16 chromosomes were assembled, with a scaffold N50 length of 33.7 Mb and a BUSCO complete gene percentage of 98.3%. J. mandshurica displays a close sequence relationship with Juglans cathayensis, with a divergence time of 13.8 million years ago. Combining the high-quality genome, transcriptome, and metabolomics data, we constructed a gene-to-metabolite network and identified 566 core and conserved differentially expressed genes, which may be involved in juglone biosynthesis. Five CYP450 genes were found that may contribute to juglone accumulation. NAC, bZip, NF-YA, and NF-YC are positively correlated with the juglone content. Some candidate regulators (e.g., FUS3, ABI3, LEC2, and WRI1 transcription factors) involved in the regulation of lipid biosynthesis were also identified. Conclusions Our genomic data provide new insights into the evolution of the walnut genome and create a new platform for accelerating molecular breeding and improving the comprehensive utilization of these economically important tree species

A Facile Route to Construct SiCO Nanospheres with Tunable Sizes

Natural Science Foundation of China [51175444, 51075344, 61274120]; Fundamental Research Funds for the Central Universities (Xiamen University) [2011121002]; Xiamen Municipal Bureau of Science and Technology [3502Z20126006]; Shenzhen City Science and Technology Innovation Committee [JCYJ20120618155425009]; National Science and Technology Major Project of the Ministry of Science and Technology of China [2011ZX02709-002]We report a facile route to synthesize SiCO nanospheres using Pluronic F127/ polyvinylsilazane (PVSZ) mixed micelles as a template, in which PVSZ selectively swells with the PEO core of the F127 micelles. The thermal degradation of the F127/ PVSZ mixed micelles leads to the formation of SiCO nanospheres. The size of the resultant SiCO nanospheres can be tuned in the range from 25 nm to 75 nm by controlling annealing time at 70 degrees C

The MAO Inhibitor Tranylcypromine Alters LPS- and A beta-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD

Monoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcypromine can regulate LPS- and/or Aβ-induced neuroinflammation in the brain has not been well-studied. In the present study, we found that tranylcypromine selectively altered LPS-induced proinflammatory cytokine levels in BV2 microglial cells but not primary astrocytes. In addition, tranylcypromine modulated LPS-mediated TLR4/ERK/STAT3 signaling to alter neuroinflammatory responses in BV2 microglial cells. Importantly, tranylcypromine significantly reduced microglial activation as well as proinflammatory cytokine levels in LPS-injected wild-type mice. Moreover, injection of tranylcypromine in 5xFAD mice (a mouse model of AD) significantly decreased microglial activation but had smaller effects on astrocyte activation. Taken together, our results suggest that tranylcypromine can suppress LPS- and Aβ-induced neuroinflammatory responses in vitro and in vivo.1

Case report: TP53 and RB1 loss may facilitate the transformation from lung adenocarcinoma to small cell lung cancer by expressing neuroendocrine markers

IntroductionTransformation from lung adenocarcinoma (LUAD) to small cell lung cancer (SCLC) is one of the mechanisms responsible for acquired EGFR-TKIs resistance. Although it rarely happens this event determines a rapid disease deterioration and needs specific treatment.Patient and methodWe report a case of 75-year-old LUAD female with a p.L858R mutation in Epidermal Growth Factor Receptor (EGFR) who presented with SCLC transformation after responding to first line osimertinib treatment for only 6 months. To understand the underlying molecular mechanism, we retrospectively sequenced the first (LUAD) and the second (SCLC) biopsy using a 56 multi-gene panel. Immunohistochemistry (IHC) staining and Fluorescence In Situ Hybridization (FISH) was applied to confirm the genetic aberrations identified.ResultsEGFR p.E709A and p.L858R, Tumor Protein p53 (TP53) p.A159D and Retinoblastoma 1 (RB1) c.365-1G>A were detected in both the diagnostic LUAD and transformed SCLC samples. A high copy number gain for Proto-Oncogene C-Myc (MYC) and a Phosphoinositide 3-Kinase Alpha (PIK3CA) p.E545K mutation were found in the transformed sample specifically. Strong TP53 staining and negative RB1 staining were observed in both LUAD and SCLC samples, but FISH only identified MYC amplification in SCLC tissue.ConclusionWe consider the combined presence of MYC amplification with mutations in TP53 and RB1 as drivers of SCLC transformation. Our results highlight the need to systematically evaluate TP53 and RB1 status in LUAD patients to offer a different therapeutic strategy

Atypical radio pulsations from magnetar SGR 1935+2154

Magnetars are neutron stars with extremely strong magnetic fields, frequently powering high-energy activity in X-rays. Pulsed radio emission following some X-ray outbursts have been detected, albeit its physical origin is unclear. It has long been speculated that the origin of magnetars' radio signals is different from those from canonical pulsars, although convincing evidence is still lacking. Five months after magnetar SGR 1935+2154's X-ray outburst and its associated Fast Radio Burst (FRB) 20200428, a radio pulsar phase was discovered. Here we report the discovery of X-ray spectral hardening associated with the emergence of periodic radio pulsations from SGR 1935+2154 and a detailed analysis of the properties of the radio pulses. The complex radio pulse morphology, which contains both narrow-band emission and frequency drifts, has not been seen before in other magnetars, but is similar to those of repeating FRBs - even though the luminosities are many orders of magnitude different. The observations suggest that radio emission originates from the outer magnetosphere of the magnetar, and the surface heating due to the bombardment of inward-going particles from the radio emission region is responsible for the observed X-ray spectral hardening.Comment: 47 pages, 11 figure

A Role for Phosphatidic Acid in the Formation of “Supersized” Lipid Droplets

Lipid droplets (LDs) are important cellular organelles that govern the storage and turnover of lipids. Little is known about how the size of LDs is controlled, although LDs of diverse sizes have been observed in different tissues and under different (patho)physiological conditions. Recent studies have indicated that the size of LDs may influence adipogenesis, the rate of lipolysis and the oxidation of fatty acids. Here, a genome-wide screen identifies ten yeast mutants producing “supersized” LDs that are up to 50 times the volume of those in wild-type cells. The mutated genes include: FLD1, which encodes a homologue of mammalian seipin; five genes (CDS1, INO2, INO4, CHO2, and OPI3) that are known to regulate phospholipid metabolism; two genes (CKB1 and CKB2) encoding subunits of the casein kinase 2; and two genes (MRPS35 and RTC2) of unknown function. Biochemical and genetic analyses reveal that a common feature of these mutants is an increase in the level of cellular phosphatidic acid (PA). Results from in vivo and in vitro analyses indicate that PA may facilitate the coalescence of contacting LDs, resulting in the formation of “supersized” LDs. In summary, our results provide important insights into how the size of LDs is determined and identify novel gene products that regulate phospholipid metabolism

Exchange Reactions between Alkanethiolates and Alkaneselenols on Au{111}

When alkanethiolate self-assembled monolayers on Au{111} are exchanged with alkaneselenols from solution, replacement of thiolates by selenols is rapid and complete, and is well described by perimeter-dependent island growth kinetics. The monolayer structures change as selenolate coverage increases, from being epitaxial and consistent with the initial thiolate structure to being characteristic of selenolate monolayer structures. At room temperature and at positive sample bias in scanning tunneling microscopy, the selenolate-gold attachment is labile, and molecules exchange positions with neighboring thiolates. The scanning tunneling microscope probe can be used to induce these place-exchange reactions