First Detection of 12CO (1--0) Emission from Two Narrow-Line Seyfert 1 Galaxies

In order to investigate how the growth of galactic bulges progresses with the growth of central black holes (BHs), we observed molecular gas (fuel for the coming star formation) in possibly young active galaxies, narrow-line Seyfert 1 galaxies (NLS1s). We present the results of radio observations of 12CO(1--0) using the Nobeyama Millimeter Array (with 2--4 kpc spatial resolution) for two FIR-bright NLS1s, yielding the first detection of their CO emission. Corresponding molecular--gas masses M(H2) of (1-3) X 109 Msun are the 2nd and 4th largest ones among NLS1s. By estimating dynamical masses and bulge masses M(bulge) for these two NLS1s using CO channel map and CO line widths, we found M(H2) amount to 0.13--0.35 of these masses. Taking account the star formation efficiency (~ 0.1), the increase in M(bulge) in those NLS1s in the near future (~< 10^{7.5} yr) is expected not to be a huge fraction (1--5% of the preexisting stars). Bulge growth may have finished before BH growth, or bulge--BH coevolution may proceed with many, occasional discrete events, where one coevolution event produces only a small amount of mass growth of BHs and of bulges. We also discuss the ratios of star-formation rate--to--gas accretion rate onto BHs, finding that two NLS1s have very small ratios (~ 1) compared with the M(bulge)/M(BH) ratios found in active and inactive galaxies (~ 700). This huge difference suggests either the non-overlapped coevolution, long star formation duration or temporarily high accretion rate during NLS1 phase.Comment: 29 pages, 8 figures, Accepted for publication in The Astrophysical Journa

A peculiar HI cloud near the distant globular cluster Pal 4

We present 21-cm observations of four Galactic globular clusters, as part of the on-going GALFA-HI Survey at Arecibo. We discovered a peculiar HI cloud in the vicinity of the distant (109 kpc) cluster Pal 4, and discuss its properties and likelihood of association with the cluster. We conclude that an association of the HI cloud and Pal 4 is possible, but that a chance coincidence between Pal 4 and a nearby compact high-velocity cloud cannot be ruled out altogether. New, more stringent upper limits were derived for the other three clusters: M 3, NGC 5466, and Pal 13. We briefly discuss the fate of globular cluster gas and the interaction of compact clouds with the Galactic Halo gas.Comment: Accepted for publication in MNRA

The dynamics and star-forming potential of the massive Galactic centre cloud G0.253+0.016

Context: The massive infrared dark cloud G0.253+0.016 projected ~45 pc from the Galactic centre contains ~105 M⊙ of dense gas whilst being mostly devoid of observed star-formation tracers. Aims: Our goals are therefore to scrutinise the physical properties, dynamics and structure of this cloud with reference to its star-forming potential. Methods: We have carried out a concerted SMA and IRAM 30 m study of this enigmatic cloud in dust continuum, CO isotopologues, several shock tracing molecules, as well as H2CO to trace the gas temperature. In addition, we include ancillary far-IR and sub-mm Herschel and SCUBA data in our analysis. Results: We detect and characterise a total of 36 dust cores within G0.253+0.016 at 1.3 mm and 1.37 mm, with masses between 25 and approximately 250 M⊙, and find that the kinetic temperature of the gas traced by H2CO ratios is >320 K on size-scales of ~0.15 pc. Analysis of the position–velocity diagrams of our observed lines shows broad linewidths and strong shock emission in the south of the cloud, indicating that G0.253+0.016 is colliding with another cloud at vLSR ~ 70 km s-1. We confirm via an analysis of the observed dynamics in the Central Molecular Zone that it is an elongated structure, orientated with Sgr B2 closer to the Sun than Sgr A*, however our results suggest that the actual geometry may be more complex than an elliptical ring. We find that the column density probability distribution function of G0.253+0.016 derived from SMA and SCUBA dust continuum emission is log-normal with no discernible power-law tail, consistent with little star formation, and that its width can be explained in the framework of theory predicting the density structure of clouds created by supersonic, magnetised turbulence. We also present the Δ-variance spectrum of this region, a proxy for the density power spectrum of the cloud, and show it is consistent with that expected for clouds with no current star formation. Finally, we show that even after determining a scaled column density threshold for star formation by incorporating the effects of the increased turbulence in the cloud, we would still expect ten stars with masses >15 M⊙ to form in G0.253+0.016. If these cannot be accounted for by new radio continuum observations, then further physical aspects may be important, such as the background column density level, which would turn an absolute column density threshold for star formation into a critical over-density. Conclusions: We conclude that G0.253+0.016 contains high-temperatures and wide-spread shocks, displaying evidence of interaction with a nearby cloud which we identify at vLSR ~ 70 km s-1. Our analysis of the structure of the cloud can be well-explained by theory of magnetised turbulence, and is consistent with little or no current star formation. Using G0.253+0.016 as a test-bed of the conditions required for star formation in a different physical environment to that of nearby clouds, we also conclude that there is not one column density threshold for star formation, but instead this value is dependant on the local physical conditions

Identification of a human neonatal immune-metabolic network associated with bacterial infection

Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis

Synthesis, Biological Evaluation and Mechanism Studies of Deoxytylophorinine and Its Derivatives as Potential Anticancer Agents

Previous studies indicated that (+)-13a-(S)-Deoxytylophorinine (1) showed profound anti-cancer activities both in vitro and in vivo and could penetrate the blood brain barrier to distribute well in brain tissues. CNS toxicity, one of the main factors to hinder the development of phenanthroindolizidines, was not obviously found in 1. Based on its fascinating activities, thirty-four derivatives were designed, synthesized; their cytotoxic activities in vitro were tested to discover more excellent anticancer agents. Considering the distinctive mechanism of 1 and interesting SAR of deoxytylophorinine and its derivatives, the specific impacts of these compounds on cellular progress as cell signaling transduction pathways and cell cycle were proceeded with seven representative compounds. 1 as well as three most potent compounds, 9, 32, 33, and three less active compounds, 12, 16, 35, were selected to proform this study to have a relatively deep view of cancer cell growth-inhibitory characteristics. It was found that the expressions of phospho-Akt, Akt, phospho-ERK, and ERK in A549 cells were greater down-regulated by the potent compounds than by the less active compounds in the Western blot analysis. To the best of our knowledge, this is the first report describing phenanthroindolizidines alkaloids display influence on the crucial cell signaling proteins, ERK. Moreover, the expressions of cyclin A, cyclin D1 and CDK2 proteins depressed more dramatically when the cells were treated with 1, 9, 32, and 33. Then, these four excellent compounds were subjected to flow cytometric analysis, and an increase in S-phase was observed in A549 cells. Since the molecular level assay results of Western blot for phospho-Akt, Akt, phospho-ERK, ERK, and cyclins were relevant to the potency of compounds in cellular level, we speculated that this series of compounds exhibit anticancer activities through blocking PI3K and MAPK signaling transduction pathways and interfering with the cell cycle progression

Gene Coexpression Network Analysis as a Source of Functional Annotation for Rice Genes

With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions/treatments have also been used to create coexpression networks to help examine particular biological processes. Gene networks derived from either condition-dependent or condition-independent data can be difficult to interpret if a large number of genes and connections are present. However, algorithms exist to identify modules of highly connected and biologically relevant genes within coexpression networks. In this study, we have used publicly available rice (Oryza sativa) gene expression data to create gene coexpression networks using both condition-dependent and condition-independent data and have identified gene modules within these networks using the Weighted Gene Coexpression Network Analysis method. We compared the number of genes assigned to modules and the biological interpretability of gene coexpression modules to assess the utility of condition-dependent and condition-independent gene coexpression networks. For the purpose of providing functional annotation to rice genes, we found that gene modules identified by coexpression analysis of condition-dependent gene expression experiments to be more useful than gene modules identified by analysis of a condition-independent data set. We have incorporated our results into the MSU Rice Genome Annotation Project database as additional expression-based annotation for 13,537 genes, 2,980 of which lack a functional annotation description. These results provide two new types of functional annotation for our database. Genes in modules are now associated with groups of genes that constitute a collective functional annotation of those modules. Additionally, the expression patterns of genes across the treatments/conditions of an expression experiment comprise a second form of useful annotation

Gene Expression Profiles in Parkinson Disease Prefrontal Cortex Implicate FOXO1 and Genes under Its Transcriptional Regulation

Parkinson disease (PD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN) region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9) of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR–significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression–SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD–relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms

Modes of Gene Duplication Contribute Differently to Genetic Novelty and Redundancy, but Show Parallels across Divergent Angiosperms

BACKGROUND: Both single gene and whole genome duplications (WGD) have recurred in angiosperm evolution. However, the evolutionary effects of different modes of gene duplication, especially regarding their contributions to genetic novelty or redundancy, have been inadequately explored. RESULTS: In Arabidopsis thaliana and Oryza sativa (rice), species that deeply sample botanical diversity and for which expression data are available from a wide range of tissues and physiological conditions, we have compared expression divergence between genes duplicated by six different mechanisms (WGD, tandem, proximal, DNA based transposed, retrotransposed and dispersed), and between positional orthologs. Both neo-functionalization and genetic redundancy appear to contribute to retention of duplicate genes. Genes resulting from WGD and tandem duplications diverge slowest in both coding sequences and gene expression, and contribute most to genetic redundancy, while other duplication modes contribute more to evolutionary novelty. WGD duplicates may more frequently be retained due to dosage amplification, while inferred transposon mediated gene duplications tend to reduce gene expression levels. The extent of expression divergence between duplicates is discernibly related to duplication modes, different WGD events, amino acid divergence, and putatively neutral divergence (time), but the contribution of each factor is heterogeneous among duplication modes. Gene loss may retard inter-species expression divergence. Members of different gene families may have non-random patterns of origin that are similar in Arabidopsis and rice, suggesting the action of pan-taxon principles of molecular evolution. CONCLUSION: Gene duplication modes differ in contribution to genetic novelty and redundancy, but show some parallels in taxa separated by hundreds of millions of years of evolution

Systematic review of the evidence relating FEV1 decline to giving up smoking

<p>Abstract</p> <p>Background</p> <p>The rate of forced expiratory volume in 1 second (FEV₁) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta.</p> <p>Methods</p> <p>Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors.</p> <p>Results</p> <p>Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex.</p> <p>Conclusion</p> <p>The available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV₁decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products.</p

Methodology of calculation of construction and hydrodynamic parameters of a foam layer apparatus for mass-transfer processes

Промислова реалізація методу стабілізації газорідинного шару дозволяє значно розширити галузь застосування пінних апаратів і відкриває нові можливості інтенсифікації технологічних процесів з одночасним створенням маловідходних технологій. У статті встановлені основні параметри, що впливають на гідродинаміку пінних апаратів, розглянуті основні конструкції та режими роботи пінних апаратів. Виявлено зв'язок гідродинамічних параметрів. Розглянуто гідродинамічні закономірності пінного шару. Вказані фактори, що впливають на процес масообміну, як в газовій, так і в рідкій фазах. Проведений аналіз ряду досліджень показав, що перспективним напрямком інтенсифікації процесу масообміну є розробка апаратів з трифазним псевдозрідженим шаром зрошуваної насадки складних форм із сітчастих матеріалів. Отже, необхідне проведення спеціальних досліджень гідродинамічних режимів роботи апарату з сітчастою насадкою і визначенням параметрів, що впливають на швидкість переходу насадки з одного режиму в інший.Industrial implementation of the stabilization method of the gas-liquid layer can significantly expand the field of use of foaming apparatus and opens up new opportunities for intensifying technological processes with the simultaneous creation of low-waste technologies. The article establishes the basic parameters influencing the hydrodynamics of foam apparatus, considers the basic constructions and operating modes of foam apparatus. The connection of hydrodynamic parameters is revealed. The hydrodynamic laws of the foam layer are considered. The indicated factors affecting the process of mass transfer, both in the gas and in the liquid phases. The conducted analysis of a number of studies showed that the perspective direction of intensification of the mass transfer process is the development of apparatuses with a three-phase fluidized bed of an irrigated nozzle of complex forms with mesh materials