Competition between Allowed and First-Forbidden β Decay: The Case of Hg 208 → Tl 208

6 pags., 4 figs., 1 tab.The β decay of Hg208 into the one-proton hole, one neutron-particle Tl81208127 nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N>126, Z<82 quadrant of neutron-rich nuclei. While both negative and positive parity states with spin 0 and 1 are expected within the Qβ window, only three negative parity states are populated directly in the β decay. The data provide a unique test of the competition between allowed Gamow-Teller and Fermi, and first-forbidden β decays, essential for the understanding of the nucleosynthesis of heavy nuclei in the rapid neutron capture process. Furthermore, the observation of the parity changing 0+→0-β decay where the daughter state is core excited is unique, and can provide information on mesonic corrections of effective operators.This work was supported by the European Union under Contracts No. 262010 (ENSAR) and No. 654002 (ENSAR2), the Science and Technology Facilities Council (UK), the German BMBF under Contract No. 05P18PKCIA and “Verbundprojekt 05P2018,” the MINECO Projects No. FPA2015-65035-P, No. RTI2018- 098868-B-I00, No. FPA2015-64969-P, and No. FPA2017- 87568-P (Spain), FWO-Vlaanderen (Belgium), GOA/ 2015/010 (BOF KU Leuven), the Excellence of Science programme (EOS-FWO), the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office (BriX network P7/12), the Romanian IFA project CERN-RO/ISOLDE and the Polish National Science Centre under Contracts No. UMO-2015/18/M/ST2/00523 and No. UMO-2019/33/N/ST2/03023. P. H. R. and S. M. J. acknowledge support from the UK Department for Business, Energy and Industrial Strategy via the National Measurement Office. Zs. P. acknowledges support from the ExtreMe Matter Institute EMMI at the GSI Helmholtzzentrum fr Schwerionenforschung, Darmstadt, Germa

Genetic susceptibility to hepatic sinusoidal obstruction syndrome in pediatric patients undergoing hematopoietic stem cell transplantation

Sinusoidal obstruction syndrome (SOS) is a well-recognized and potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). SOS arises from endothelial cell damage and hepatocellular injury mostly due to the transplantation conditioning regimens but also to other patient, disease, and treatment-related factors. Understanding risk factors associated with the development of SOS is critical for early initiation of treatment or prophylaxis. The knowledge about genetic contribution is limited; few studies investigated so far selected a set of genes. To get more comprehensive insight in the genetic component, we performed an exome-wide association study using genetic variants derived from whole-exome sequencing. The analyses were performed in a discovery cohort composed of 87 pediatric patients undergoing HSCT following a busulfan-containing conditioning regimen. Eight lead single-nucleotide polymorphisms (SNPs) were identified after correction for multiple testing and subsequently analyzed in a validation cohort (n = 182). Three SNPs were successfully replicated, including rs17146905 ( P = .001), rs16931326 ( P = .04), and rs2289971 ( P = .03), located respectively in the UGT2B10, BHLHE22, and KIAA1715 genes. UGT2B10 and KIAA1715 were retained in a multivariable model while controlling for nongenetic covariates and previously identified risk variants in the GSTA1 promoter. The modulation of associations by conditioning regimens was noted; KIAA1715 was dependent on the intensity of the conditioning regimen, whereas the effect of UGT2B10 was equally applicable to all of them. Combined effect of associated loci was also observed ( P = .00006) with a genotype-related SOS risk of 9.8. To our knowledge, this is the first study addressing the genetic component of SOS at an exome-wide level and identifying novel genetic variations conferring a higher risk of SOS, which might be useful for personalized prevention and treatment strategies. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.Transplantation and immunomodulatio

Association between the magnitude of intravenous busulfan exposure and development of hepatic veno-occlusive disease in children and young adults undergoing myeloablative allogeneic hematopoietic cell transplantation

Intravenous busulfan is widely used as part of myeloablative conditioning regimens in children and young adults undergoing allogeneic hematopoietic cell transplantation (HCT). Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious clinical problem observed with busulfan-based conditioning HCT. The development of VOD/SOS may be associated with busulfan exposure. Getting more insight into the association between busulfan exposure and the development of VOD/SOS enables further optimization of dos-ing and treatment strategies. The objective of this study was to assess the association between the magnitude of busulfan exposure and the occurrence of VOD/SOS in children and young adults undergoing myeloablative con-ditioning with a busulfan-containing regimen before allogeneic HCT. In this observational study we included all patients who underwent allogeneic HCT with intravenous busulfan as part of the conditioning regimen at 15 pediatric transplantation centers between 2000 and 2015. The endpoint was the development of VOD/SOS. The magnitude of busulfan exposure was estimated using nonlinear mixed effect modeling and expressed as the maximal concentration (Cmax; day 1 and day 1 to 4 Cmax), cumulative area under the curve (AUC; day 1, high-est 1-day AUC in 4 days, and 4-day cumulative AUC), cumulative time above a concentration of 300 mg/L, and clearance on day 1. A total of 88 out of 697 patients (12.6%) developed VOD/SOS. The number of alkylators in the conditioning regimen was a strong effect modifier; therefore we stratified the regression analysis for the number of alkylators. For patients receiving only busulfan as one alkylator (36.3%, n = 253), cumulative busulfan exposure (>78 mg x h/L) was associated with increased VOD/SOS risk (12.6% versus 4.7%; odds ratio [OR] = 2.95, 95% confidence interval [CI] 1.13 to 7.66). For individuals receiving busulfan with one or two addi-tional alkylators (63.7%, n = 444), cumulative busulfan exposure (78 mg x h/L) did not further increase the risk of VOD/SOS (15.4% versus 15.2%; OR = 1.03, 95% CI 0.61 to 1.75). The effect of the magnitude of busulfan exposure on VOD/SOS risk in children and young adults undergoing HCT is dependent on the number of alkylators. In patients receiving busulfan as the only alkylator, higher cumulative busulfan exposure increased the risk of VOD/SOS, whereas in those receiving multiple alkylators, the magnitude of busulfan expo-sure did not further increase this risk. Transplantation and immunomodulatio

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

Nonlinear instability and convection in a vertically vibrated granular bed

The nonlinear instability of the density-inverted granular Leidenfrost state and the resulting convective motion in strongly shaken granular matter are analysed via a weakly nonlinear analysis of the hydrodynamic equations. The base state is assumed to be quasi-steady and the effect of harmonic shaking is incorporated by specifying a constant granular temperature at the vibrating plate. Under these mean-field assumptions, the base-state temperature decreases with increasing height away from the vibrating plate, but the density profile consists of three distinct regions: (i) a collisional dilute layer at the bottom, (ii) a levitated dense layer at some intermediate height and (iii) a ballistic dilute layer at the top of the granular bed. For the nonlinear stability analysis (Shukla & Alam, J. Fluid Mech., vol. 672, 2011b, pp. 147–195), the nonlinearities up to cubic order in the perturbation amplitude are retained, leading to the Landau equation, and the related adjoint stability problem is formulated taking into account appropriate boundary conditions. The first Landau coefficient and the related modal eigenfunctions (the fundamental mode and its adjoint, the second harmonic and the base-flow distortion, and the third harmonic and the cubic-order distortion to the fundamental mode) are calculated using a spectral-based numerical method. The genesis of granular convection is shown to be tied to a supercritical pitchfork bifurcation from the density-inverted Leidenfrost state. Near the bifurcation point the equilibrium amplitude (Ae) is found to follow a square-root scaling law, Ae∼Δ−−√, with the distance Δ from the bifurcation point. We show that the strength of convection (measured in terms of velocity circulation) is maximal at some intermediate value of the shaking strength, with weaker convection at both weaker and stronger shaking. Our theory predicts that at very strong shaking the convective motion remains concentrated only near the top surface, with the bulk of the expanded granular bed resembling the conduction state of a granular gas, dubbed as a floating-convection state. The linear and nonlinear patterns of the density and velocity fields are analysed and compared with experiments qualitatively. Evidence of 2:1 resonance is shown for certain parameter combinations. The influences of bulk viscosity, effective Prandtl number, shear work and free-surface boundary conditions on nonlinear equilibrium states are critically assessed

Nonlinear instability and convection in a vertically vibrated granular bed

The nonlinear instability of the density-inverted granular Leidenfrost state and the resulting convective motion in strongly shaken granular matter are analysed via a weakly nonlinear analysis of the hydrodynamic equations. The base state is assumed to be quasi-steady and the effect of harmonic shaking is incorporated by specifying a constant granular temperature at the vibrating plate. Under these mean-field assumptions, the base-state temperature decreases with increasing height away from the vibrating plate, but the density profile consists of three distinct regions: (i) a collisional dilute layer at the bottom, (ii) a levitated dense layer at some intermediate height and (iii) a ballistic dilute layer at the top of the granular bed. For the nonlinear stability analysis (Shukla & Alam, J. Fluid Mech. vol. 672, 2011b, pp. 147-195), the nonlinearities up to cubic order in the perturbation amplitude are retained, leading to the Landau equation, and the related adjoint stability problem is formulated taking into account appropriate boundary conditions. The first Landau coefficient and the related modal eigenfunctions (the fundamental mode and its adjoint, the second harmonic and the base-flow distortion, and the third harmonic and the cubic-order distortion to the fundamental mode) are calculated using a spectral-based numerical method. The genesis of granular convection is shown to be tied to a supercritical pitchfork bifurcation from the density-inverted Leidenfrost state. Near the bifurcation point the equilibrium amplitude (Ae) is found to follow a square-root scaling law, Ae ∼ Δ, with the distance Δ from the bifurcation point. We show that the strength of convection (measured in terms of velocity circulation) is maximal at some intermediate value of the shaking strength, with weaker convection at both weaker and stronger shaking. Our theory predicts that at very strong shaking the convective motion remains concentrated only near the top surface, with the bulk of the expanded granular bed resembling the conduction state of a granular gas, dubbed as a floating-convection state. The linear and nonlinear patterns of the density and velocity fields are analysed and compared with experiments qualitatively. Evidence of 2:1 resonance is shown for certain parameter combinations. The influences of bulk viscosity, effective Prandtl number, shear work and free-surface boundary conditions on nonlinear equilibrium states are critically assessed.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Nanomaterial by Sol-Gel Method: Synthesis and Application

The sol-gel process is a more chemical method (wet chemical method) for the synthesis of various nanostructures, especially metal oxide nanoparticles. In this method, the molecular precursor (usually metal alkoxide) is dissolved in water or alcohol and converted to gel by heating and stirring by hydrolysis/alcoholysis. Since the gel obtained from the hydrolysis/alcoholysis process is wet or damp, it should be dried using appropriate methods depending on the desired properties and application of the gel. For example, if it is an alcoholic solution, the drying process is done by burning alcohol. After the drying stage, the produced gels are powdered and then calcined. The sol-gel method is a cost-effective method and due to the low reaction temperature there is good control over the chemical composition of the products. The sol-gel method can be used in the process of making ceramics as a molding material and can be used as an intermediate between thin films of metal oxides in various applications. The materials obtained from the sol-gel method are used in various optical, electronic, energy, surface engineering, biosensors, and pharmaceutical and separation technologies (such as chromatography). The sol-gel method is a conventional and industrial method for the synthesis of nanoparticles with different chemical composition. The basis of the sol-gel method is the production of a homogeneous sol from the precursors and its conversion into a gel. The solvent in the gel is then removed from the gel structure and the remaining gel is dried. The properties of the dried gel depend significantly on the drying method. In other words, the "removing solvent method"is selected according to the application in which the gel will be used. Dried gels in various ways are used in industries such as surface coating, building insulation, and the production of special clothing. It is worth mentioning that, by grinding the gel by special mills, it is possible to achieve nanoparticles

A novel, highly selective inhibitor of pestivirus replication that targets the viral RNA-dependent RNA polymerase.

&lt;p&gt;We report on the highly potent and selective antipestivirus activity of 5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP). The 50% effective concentration (EC50) for inhibition of bovine viral diarrhea virus (BVDV)-induced cytopathic effect formation was 0.04 +/- 0.01 microM. Comparable reduction of viral RNA synthesis (EC50 = 0.12 +/- 0.02 microM) and production of infectious virus (EC50= 0.074 +/- 0.003 microM) were observed. The selectivity index (ratio of 50% cytostatic concentration/EC50) of BPIP was approximately 2,000. BPIP was inactive against the hepatitis C virus subgenomic replicon and yellow fever virus but demonstrated weak activity against GB virus. Drug-resistant mutants were at least 300-fold less susceptible to BPIP than wild-type virus; showed cross-resistance to N-propyl-N-[2-(2H-1,2,4-triazino[5,6-b]indol-3-ylthio)ethyl]-1-propanamine (VP32947), and carried the F224S mutation in the viral RNA-dependent RNA polymerase (RdRp). When the F224S mutation was introduced into an infectious clone, the drug-resistant phenotype was obtained. BPIP did not inhibit the in vitro activity of recombinant BVDV RdRp, but did inhibit the activity of replication complexes (RCs). Computational docking revealed that F224 is located at the top of the finger domain of the polymerase. Docking of BPIP in the crystal structure of the BVDV RdRp revealed aromatic ring stacking, some hydrophobic contacts, and a hydrogen bond. Since two structurally unrelated compounds, i.e., BPIP and VP32947, target the same region of the BVDV RdRp, this position may be expected to be critical in the functioning of the polymerase or assembly of the RC. The potential of BPIP for the treatment of pestivirus and hepacivirus infections is discussed.&lt;/p&gt;</p

GSTA1 diplotypes affect busulfan clearance and toxicity in children undergoing allogeneic hematopoietic stem cell transplantation: a multicenter study

Transplantation and immunomodulatio