6′-Bromo-1′H-spiro­[cyclo­hexane-1,2′-pyrido[2,3-d]pyrimidin]-4′(3′H)-one

The title compound, C12H14BrN3O, is built up from two fused six-membered rings and one six-membered ring linked through a spiro C atom. The hydro­pyrimidine ring has an envelope conformation and the cyclo­hexane ring is in a chair conformation. In the crystal, mol­ecules are linked by N—H⋯O and N—H⋯N hydrogen bonds, forming a mol­ecular tape along the b axis

Merger-induced star formation in low-metallicity dwarf galaxy NGC 4809/4810

The physical mechanisms driving starbursts in dwarf galaxies are unclear, and the effects of mergers on star formation in these galaxies are still uncertain. We explore how the merger process affects star formation in metal-poor dwarf galaxies by analyzing high-spatial-resolution ($\sim$ 70 pc) integral field spectrograph observations of ionized gas. We use archival data from the Very Large Telescope/Multi Unit Spectroscopic Explorer to map the spatial distribution of strong emission lines (e.g., $\rm H\beta$, $\rm H\alpha$, $\rm [OIII]\lambda5007$, $\rm [NII]\lambda6583$, etc) in the nearby merging star-forming dwarf galaxy system NGC 4809/4810. We identify approximately 112 star-forming knots scattered among the two galaxies, where the gas-phase metallicity distribution is inhomogeneous and mixing with metal-poor and metal-rich ionized gas. Star-forming knots at the interacting region show lower metallicity, the highest star formation rates (SFRs) and SFR to resolved main-sequence-relation (rMSR) ratios. Ionized gas exhibits an obvious northeast-southwest velocity gradient in NGC 4809, while seemingly mixed in NGC 4810. High virial parameters and the stellar mass-size relation of HII regions indicate that these regions are dominated by direct radiation pressure from massive stars/clusters and persistently expanding. We find two different stellar mass surface density-stellar age relations in NGC 4809 and NGC 4810, and the stellar ages of NGC 4810 are systematically younger than in NGC 4809. Our study suggests that the merging stage of two dwarf galaxies can induce starburst activities at the interaction areas, despite the metal-deficient environment. Considering the high specific SFRs and different stellar ages, we propose that the interaction initially triggered star formation in NGC 4809 and then drove star formation in NGC 4810.Comment: 13 pages, 12 figures; accepted for publication in A&

Factor analyses of a social support scale using two methods

Purpose: Evaluation and comparison of the factor structure of the Medical Outcomes Study Social Support Survey (MOS-SSS) using both confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) with two samples of people living with HIV/AIDS in China. Methods: Secondary analyses were conducted with data from two comparable samples of 320 people living with HIV/AIDS from the same hospital using the same inclusion criteria. The first sample of 120 was collected in 2006, and the second sample of 200 was collected in 2012. For each sample, CFA was first performed on the original four-factor structure to check model fit, followed by EFA to explore other factor structures and a subsequent CFA for model fit statistics to be compared to the original four-factor CFA. Results: In both samples, CFA on the originally hypothesized four-factor structure yielded an acceptable model fit. The EFA yielded a two-factor solution in both samples, with different items included in each factor for the two samples. Comparison of CFA on the a priori four-factor structure and the new two-factor structure in both samples indicated that both factor structures were of acceptable model fit, with the four-factor model performing slightly better than the two-factor model. Conclusion: Factor structure of the MOS-SSS is method-dependent, with CFA supporting a four-factor structure, while EFA yielded a two-factor structure in two separate samples. We need to be careful in selecting the analytic method when applying the MOS-SSS to various samples and choose the factor structure that best fits the theoretical model

Antiretroviral Therapy (ART) Side Effect Impacted on Quality of Life, and Depressive Symptomatology: A Mixed-Method Study

Antiretroviral therapy (ART) is known for its side effects. In this paper, we describe ART side effects as experienced by Chinese HIV+ individuals. This study presents two stages of a research project, combining qualitative in-depth interviews (29 HIV+ participants) with quantitative statistical data analysis (N = 120). All data was collected between July 2005 to March 2008 at Beijing\u27s Ditan Hospital. Consent was obtained from each participant for the qualitative interview and again for the quantitative survey. During in-depth interviews, Chinese HIV+ patients reported experiencing digestive discomfort, skin rashes, numbness, memory loss, nightmares, and dizziness, which not only brought them physical discomfort, but also interrupted different dimensions of their social lives. Furthermore, multiple regression analyses revealed that those who reported more severe side effects also experienced greater depressive mood after controlling for other clinical and psychosocial factors. ART side effects are one of the primary reasons causing HIV+ individuals to delay or stop taking life-saving medication; therefore, clinical interventions are critically needed to assist HIV+ individuals in managing ART side effects. ART side effects reinforced existing negative attitudes toward ART and lead to lower ART adherence. Future research should focus on developing culturally sensitive interventions to enhance HIV+ selfmanagement, to alleviate physical and psychological burden from ART and HIV

A novel Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) grafted Polyethyleneimine(PCFC-g-PEI), Part 1, synthesis, cytotoxicity, and in vitro transfection study

<p>Abstract</p> <p>Background</p> <p>Polyethyleneimine (PEI), a cationic polymer, is one of the successful and widely used vectors for non-viral gene transfection <it>in vitro</it>. However, its <it>in vivo </it>application was greatly limited due to its high cytotoxicity and short duration of gene expression. To improve its biocompatibility and transfection efficiency, PEI has been modified with PEG, folic acid, and chloroquine in order to improve biocompatibility and enhance targeting.</p> <p>Results</p> <p>Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) (PCFC) was synthesized by ring-opening polymerization, and PCFC-<it>g</it>-PEI was obtained by Michael addition reaction with GMA-PCFC-GMA and polyethyleneimine (PEI, 25 kD). The prepared PCFC-<it>g</it>-PEI was characterized by ¹H-NMR, SEC-MALLS. Meanwhile, DNA condensation, DNase I protection, the particle size and zeta potential of PCFC-<it>g</it>-PEI/DNA complexes were also determined. According to the results of flow cytometry and MTT assay, the synthesized PCFC-<it>g</it>-PEI, with considerable transfection efficiency, had obviously lower cytotoxicity against 293 T and A549 cell lines compared with that of PEI 25 kD.</p> <p>Conclusion</p> <p>The cytotoxicity and <it>in vitro </it>transfection study indicated that PCFC-<it>g</it>-PEI copolymer prepared in this paper was a novel gene delivery system with lower cytotoxicity and considerable transfection efficiency compared with commercial PEI (25 kD).</p

An Essential Role for RIG-I in Toll-like Receptor-Stimulated Phagocytosis

SummaryRetinoic acid-inducible gene-I (RIG-I) plays an important role in antiviral response by recognizing double-stranded RNA. Here we demonstrate an unanticipated role of RIG-I in Toll-like receptor (TLR)-stimulated phagocytosis. Stimulation with lipopolysaccharide (LPS), a ligand of TLR4, induced the expression of RIG-I in macrophages. Depletion of RIG-I by RNAi or gene targeting inhibited the LPS-induced phagocytosis of bacteria. Cellular processes involved in phagocytosis, such as small GTPase Cdc42/Rac1 activation, actin polymerization, and actin-regulator Arp2/3 recruitment, were also impaired in RIG-I-deficient macrophages activated by LPS. Moreover, RIG-I−/− mice were found to be more susceptible to infection with Escherichia coli as compared to wild-type mice. Thus, the regulatory functions of RIG-I are strikingly broad, including a role not only in antiviral responses but in antibacterial responses as well

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN