Methyl 5-(2-bromo­acet­yl)-2-propoxybenzoate

The title compound, C13H15BrO4, was synthesized from methyl 5-acetyl-2-hydroxy­benzoate. With the exception of the ester group and some H atoms, the molecule is planar, the average deviation from planarity being 0.086 (5) Å. The dihedral angle between the phenyl ring and the ester group is 41.6 (3)°. Adjacent mol­ecules are inter­connected by C—H⋯O bonds, generating a layered structure

Methyl 4-(3-chloro­prop­oxy)benzoate

In the crystal structure of the title compound, C11H13ClO3, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into zigzag chains along the c axis

2,3-Bis(4-bromo­phen­yl)quinoxaline

The title compound, C20H12Br2N2, was prepared by the reaction of 1-(3-bromo­phen­yl)-2-(4-bromo­phen­yl)ethane-1,2-dione with o-phenyl­enediamine in refluxing ethanol. In the mol­ecule, all bond lengths and angles are within normal ranges. The dihedral angle between the two benzene rings is 34.89 (1)°. The dihedral angles between the benzene rings and the quinoxaline system are 57.23 (1) and 36.75 (1)°. The crystal packing is stabilized by van der Waals forces

(meso-5,5,7,12,12,14-Hexamethyl-1,4,8,11-tetra­azacyclo­tetra­deca­ne)nickel(II) bis­(O,O′-dibenzyl dithio­phosphate)

In the title salt-type 1:2 adduct, [Ni(C16H36N4)](C14H14O2PS2)2 or [Ni(tet-a)][S2P(OCH2Ph)2]2, where tet-a is meso-5,5,7,12,12,14-hexa­methyl-1,4,8,11-tetra­azacyclo­tetra­decane, the [Ni(tet-a)]2+ complex cation exhibits a relatively undistorted square-planar geometry about the Ni atom, which lies on an inversion centre and is coordinated by four macrocyclic N atoms. The two O,O′-bis­(2-phenyl­meth­yl) dithio­phosphate anions act as counter-ions to balance the charge and they inter­act with the complex through N—H⋯S hydrogen bonds. Important geometric data include Ni—N distances of 1.958 (3) and 1.963 (3) Å

Epigenome-wide methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2+): a prospective cohort study in the United States.

BACKGROUND: Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test. METHODS: A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05. RESULTS: At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP. CONCLUSIONS: Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs. IMPACT: Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines

Company ‘Emigration’ and EC Freedom of Establishment: Daily Mail Revisited

Following the ECJ’s recent case law on EC freedom of establishment (the Centros, Überseering and Inspire Art cases), regulatory competition for corporate law within the European Union takes place at an early stage of the incorporation of new companies. In contrast, as regards the ‘moving out’ of companies from the country of incorporation, the ECJ once considered a tax law restriction against the transfer abroad of a company’s administrative seat as compatible with EC freedom of establishment (the Daily Mail case). For years, this decision has been regarded as applicable to all restrictions imposed by countries of incorporation, even the forced liquidation of the ‘emigrating’ company. This paper addresses the question whether EC freedom of establishment really allows Member States to place any limit on the ‘emigration’ of nationally registered companies. It argues that EC freedom of establishment covers the transfer of the administrative seat as well as the transfer of the registered office and, therefore, that the country of incorporation cannot liquidate ‘emigrating’ companies. In addition, it addresses the question whether a new Directive is needed to allow the transfer of a com- pany’s registered office and the identity-preserving company law changes. It argues that such a Directive is necessary to avoid legal uncertainty and to protect the interests of employees, creditors and minority shareholders, among others, who could be detrimentally affected by the ‘emigration’ of national companies

Comprehensive identification and analyses of the Hsf gene family in the whole-genome of three Apiaceae species

Apiaceae is a major family from Apiales and includes many important vegetable and medicinal crops. Heat shock transcription factors ( Hsf ) play important roles in heat tolerance during plant development. Here, we conducted systematic analyses of the Hsf gene family in three Apiaceae species, including 17 Apium graveolens (celery), 32 Coriandrum sativum (coriander), and 14 Daucus carota (carrot). A total of 73 Hsf genes were identified in three representative species, including Arabidopsis thaliana , Vitis vinifera , and Lactuca sativa . Whole-genome duplication played important roles in the Hsf gene family’s expansion within Apiaceae. Interestingly, we found that coriander had more Hsf genes than celery and carrot due to greater expansion and fewer losses. Twenty-seven branches of the phylogenetic tree underwent considerable positive selection in these Apiaceae species. We also explored the expression patterns of Hsf genes in three plant organs. Collectively, this study will serve as a rich gene resource for exploring the molecular mechanisms of heat tolerance. Additionally, this is the first study to report on the Hsf gene family in Apiaceae; thus, our research will provide guidance for future comparative and functional genomic studies on the Hsf gene family and others in Apiaceae

Study Protocol: insulin and its role in cancer

<p>Abstract</p> <p>Background</p> <p>Studies have shown that metabolic syndrome and its consequent biochemical derangements in the various phases of diabetes may contribute to carcinogenesis. A part of this carcinogenic effect could be attributed to hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding proteins and hence increase levels of free IGF-1. It is well established that bioactivity of free insulin growth factor 1 (IGF-1) increases tumor turnover rate. The objective is to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying the relation between insulin resistance/sensitivity and IGF-1 levels in cancer patients. We postulate that hyperinsulinaemia which prevails during initial phases of insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-1, which may contribute to process of carcinogenesis.</p> <p>Methods/Design</p> <p>Based on our pilot study results and power analysis of the same, we have designed a two group case-control study. 800 proven untreated cancer patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200 healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1 levels shall be determined in all subjects. Association between the two parameters shall be tested using suitable statistical methods.</p> <p>Discussion</p> <p>Well controlled studies in humans are essential to study the link between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study could provide insights to the role of insulin, insulin resistance, IGF-1 in carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve around insulin and insulin resistance.</p