Anomalous Heat Conduction and Anomalous Diffusion in Low Dimensional Nanoscale Systems

Thermal transport is an important energy transfer process in nature. Phonon is the major energy carrier for heat in semiconductor and dielectric materials. In analogy to Ohm's law for electrical conductivity, Fourier's law is a fundamental rule of heat transfer in solids. It states that the thermal conductivity is independent of sample scale and geometry. Although Fourier's law has received great success in describing macroscopic thermal transport in the past two hundreds years, its validity in low dimensional systems is still an open question. Here we give a brief review of the recent developments in experimental, theoretical and numerical studies of heat transport in low dimensional systems, include lattice models, nanowires, nanotubes and graphenes. We will demonstrate that the phonon transports in low dimensional systems super-diffusively, which leads to a size dependent thermal conductivity. In other words, Fourier's law is breakdown in low dimensional structures

Hypoxia Inhibits Osteogenesis in Human Mesenchymal Stem Cells through Direct Regulation of RUNX2 by TWIST

Bone loss induced by hypoxia is associated with various pathophysiological conditions, however, little is known about the effects of hypoxia and related signaling pathways on osteoblast differentiation and bone formation. Because bone marrow-derived mesenchymal stem cells (MSCs) survive under hypoxic conditions and readily differentiate into osteoblasts by standard induction protocols, they are a good in vitro model to study the effects of hypoxia on osteoblast differentiation.Using human MSCs, we discovered TWIST, a downstream target of HIF-1α, was induced under hypoxia and acted as a transcription repressor of RUNX2 through binding to the E-box located on the promoter of type 1 RUNX2. Suppression of type 1 RUNX2 by TWIST under hypoxia further inhibited the expression of BMP2, type 2 RUNX2 and downstream targets of RUNX2 in MSCs.Our findings point to the important role of hypoxia-mediated signalling in osteogenic differentiation in MSCs through direct regulation of RUNX2 by TWIST, and provide a method for modifying MSC osteogenesis upon application of these cells in fracture healing and bone reconstruction

Organometallic indolo[3,2-c]quinolines versus indolo[3,2-d]benzazepines: synthesis, structural and spectroscopic characterization, and biological efficacy

The synthesis of ruthenium(II) and osmium(II) arene complexes with the closely related indolo[3,2-c]quinolines N-(11H-indolo[3,2-c]quinolin-6-yl)-ethane-1,2-diamine (L1) and N′-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (L2) and indolo[3,2-d]benzazepines N-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-ethane-1,2-diamine (L3) and N′-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-N,N-dimethylethane-1,2-diamine (L4) of the general formulas [(η6-p-cymene)MII(L1)Cl]Cl, where M is Ru (4) and Os (6), [(η6-p-cymene)MII(L2)Cl]Cl, where M is Ru (5) and Os (7), [(η6-p-cymene)MII(L3)Cl]Cl, where M is Ru (8) and Os (10), and [(η6-p-cymene)MII(L4)Cl]Cl, where M is Ru (9) and Os (11), is reported. The compounds have been comprehensively characterized by elemental analysis, electrospray ionization mass spectrometry, spectroscopy (IR, UV–vis, and NMR), and X-ray crystallography (L1·HCl, 4·H2O, 5, and 9·2.5H2O). Structure–activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells as well as cyclin-dependent kinase (cdk) inhibition and DNA intercalation in cell-free settings have been established. The metal-free indolo[3,2-c]quinolines inhibit cancer cell growth in vitro, with IC50 values in the high nanomolar range, whereas those of the related indolo[3,2-d]benzazepines are in the low micromolar range. In cell-free experiments, these classes of compounds inhibit the activity of cdk2/cyclin E, but the much higher cytotoxicity and stronger cell cycle effects of indoloquinolines L1 and 7 are not paralleled by a substantially higher kinase inhibition compared with indolobenzazepines L4 and 11, arguing for additional targets and molecular effects, such as intercalation into DNA

Lapatinib Induces Autophagy, Apoptosis and Megakaryocytic Differentiation in Chronic Myelogenous Leukemia K562 Cells

Lapatinib is an oral, small-molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptors (EGFR, or ErbB/Her) in solid tumors. Little is known about the effect of lapatinib on leukemia. Using human chronic myelogenous leukemia (CML) K562 cells as an experimental model, we found that lapatinib simultaneously induced morphological changes resembling apoptosis, autophagy, and megakaryocytic differentiation. Lapatinib-induced apoptosis was accompanied by a decrease in mitochondrial transmembrane potential and was attenuated by the pancaspase inhibitor z-VAD-fmk, indicating a mitochondria-mediated and caspase-dependent pathway. Lapatinib-induced autophagic cell death was verified by LC3-II conversion, and upregulation of Beclin-1. Further, autophagy inhibitor 3-methyladenine as well as autophagy-related proteins Beclin-1 (ATG6), ATG7, and ATG5 shRNA knockdown rescued the cells from lapatinib-induced growth inhibition. A moderate number of lapatinib-treated K562 cells exhibited features of megakaryocytic differentiation. In summary, lapatinib inhibited viability and induced multiple cellular events including apoptosis, autophagic cell death, and megakaryocytic differentiation in human CML K562 cells. This distinct activity of lapatinib against CML cells suggests potential for lapatinib as a therapeutic agent for treatment of CML. Further validation of lapatinib activity in vivo is warranted

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

A Genome-Wide Association Study Identifies Susceptibility Variants for Type 2 Diabetes in Han Chinese

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54×10−10; odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36–1.82), and serine racemase (SRR) (P = 3.06×10−9; OR = 1.28; 95% CI = 1.18–1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65×10−10; OR = 1.29, 95% CI = 1.19–1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations

Computational Analysis of mRNA Expression Profiles Identifies MicroRNA-29a/c as Predictor of Colorectal Cancer Early Recurrence

Colorectal cancer (CRC) is one of the leading malignant cancers with a rapid increase in incidence and mortality. The recurrences of CRC after curative resection are sometimes unavoidable and often take place within the first year after surgery. MicroRNAs may serve as biomarkers to predict early recurrence of CRC, but identifying them from over 1,400 known human microRNAs is challenging and costly. An alternative approach is to analyze existing expression data of messenger RNAs (mRNAs) because generally speaking the expression levels of microRNAs and their target mRNAs are inversely correlated. In this study, we extracted six mRNA expression data of CRC in four studies (GSE12032, GSE17538, GSE4526 and GSE17181) from the gene expression omnibus (GEO). We inferred microRNA expression profiles and performed computational analysis to identify microRNAs associated with CRC recurrence using the IMRE method based on the MicroCosm database that includes 568,071 microRNA-target connections between 711 microRNAs and 20,884 gene targets. Two microRNAs, miR-29a and miR-29c, were disclosed and further meta-analysis of the six mRNA expression datasets showed that these two microRNAs were highly significant based on the Fisher p-value combination (p = 9.14×10−9 for miR-29a and p = 1.14×10−6 for miR-29c). Furthermore, these two microRNAs were experimentally tested in 78 human CRC samples to validate their effect on early recurrence. Our empirical results showed that the two microRNAs were significantly down-regulated (p = 0.007 for miR-29a and p = 0.007 for miR-29c) in the early-recurrence patients. This study shows the feasibility of using mRNA profiles to indicate microRNAs. We also shows miR-29a/c could be potential biomarkers for CRC early recurrence

The elements of human cyclin D1 promoter and regulation involved

Cyclin D1 is a cell cycle machine, a sensor of extracellular signals and plays an important role in G1-S phase progression. The human cyclin D1 promoter contains multiple transcription factor binding sites such as AP-1, NF-қB, E2F, Oct-1, and so on. The extracellular signals functions through the signal transduction pathways converging at the binding sites to active or inhibit the promoter activity and regulate the cell cycle progression. Different signal transduction pathways regulate the promoter at different time to get the correct cell cycle switch. Disorder regulation or special extracellular stimuli can result in cell cycle out of control through the promoter activity regulation. Epigenetic modifications such as DNA methylation and histone acetylation may involved in cyclin D1 transcriptional regulation

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented