Separation of Cholesterol from other Steroids Using Molecularly Imprinted Polymer Prepared by Seeded Suspension Polymerization

Micron-sized particles of cholesterol-imprinted polymers were synthesized by seeded suspension polymerization in a mixture of 2-propanol and water using polystyrene microbeads as the seeds. Methacrylic acid was employed as the functional monomer to form complexes with template (cholesterol), along with ethylene glycol dimethacrylate as the crosslinker. After removal of template molecules, the columns ( H=15 cm, Di= 0.46 cm ) packed with cholesterol-imprinted polymers were effective for the chromatographic separation of cholesterol from other steroids. When the sample of steroids was eluted isocratically at a flow-rate of Q = 0.5 mL min-1, using a mixture of acetonitrile and water (Ψ= 95:5) as the mobile phase, the retention times for estrone, -estradiol and cholesterol were respectively τ = 5.3, 12.3 and 17.2 min. The average retention times were = 5.3, 10.9 and 16.7 min respectively for estrone, progesterone and cholesterol in samples. The separation was based on the specific binding of cholesterol to recognition sites formed on the imprinted polymers. A separation factor of 1.6 for cholesterol and -estradiol was obtained. The chromatographic efficiency was dependent on the mobile phase composition. Reducing the water content in the non-polar mobile phase to zero could significantly enhance the separation. Compared with particles from bulk polymerization, the column packed with cholesterol-imprinted particles from seeded suspension polymerization had a higher chromatographic efficiency and the advantage of microanalysi

Hadronic Parity Violation and Inelastic Electron-Deuteron Scattering

We compute contributions to the parity-violating (PV) inelastic electron-deuteron scattering asymmetry arising from hadronic PV. While hadronic PV effects can be relatively important in PV threshold electro- disintegration, we find that they are highly suppressed at quasielastic kinematics. The interpretation of the PV quasielastic asymmetry is, thus, largely unaffected by hadronic PV.Comment: 27 pages, 13 figures, uses REVTeX and BibTe

Effective Actions and Phase Fluctuations in d-wave Superconductors

We study effective actions for order parameter fluctuations at low temperature in layered d-wave superconductors such as the cuprates. The order parameter lives on the bonds of a square lattice and has two amplitude and two phase modes associated with it. The low frequency spectral weights for amplitude and relative phase fluctuations is determined and found to be subdominant to quasiparticle contributions. The Goldstone phase mode and its coupling to density fluctuations in charged systems is treated in a gauge-invariant manner. The Gaussian phase action is used to study both the $c$-axis Josephson plasmon and the more conventional in-plane plasmon in the cuprates. We go beyond the Gaussian theory by deriving a coarse-grained quantum XY model, which incorporates important cutoff effects overlooked in previous studies. A variational analysis of this effective model shows that in the cuprates, quantum effects of phase fluctuations are important in reducing the zero temperature superfluid stiffness, but thermal effects are small for $T << T_c$.Comment: Some numerical estimates corrected and figures changed. to appear in PRB, Sept.1 (2000

5He ternary fission yields of 252Cf and 235U(n,f)

The relative 4He and 5He ternary fission yields were determined from a careful analysis of the energy distribution of α spectra from a new measurement with a 252Cf source and from published data on 252Cf and 235U(n,f). The kinetic energies of the 5He and 4He ternary particles were found to be approximately 11 and 16 MeV, respectively. 5He particles contribute 10-20% to the total alpha yield with the remainder originating from 4He accompanied fission

Wnt signalling and cancer stem cells

[Abstract] Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.Ministerio de Ciencia e Innovación; SAF2008-0060

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole-genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n = 109,122 individuals. We identified 59 sentinel variants (p &lt; 5 × 10−9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated that the independent signals colocalized with cell-type-specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated that our TL polygenic trait scores (PTSs) were associated with an increased risk of cancer-related phenotypes

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden