Characterization of a Deglaciated Sediment Chronosequence in the High Arctic Using Near‐Surface Geoelectrical Monitoring Methods

Accelerated climate warming is causing significant reductions in the volume of Arctic glaciers, such that previously ice-capped bare ground is uncovered, harboring soil development. Monitoring the thermal and hydrologic characteristics of soils, which strongly affect microbial activity, is important to understand the evolution of emerging terrestrial landscapes. We instrumented two sites on the forefield of a retreating Svalbard glacier, representing sediment ages of approximately 5 and 60 years since exposure. Our instrumentation included an ERT array complemented by adjacent point sensor measurements of subsurface temperature and water content. Sediments were sampled at each location and at two more additional sites (120 and 2000 years old) along a chronosequence aligned with the direction of glacial retreat. Analysis suggests older sediments have a lower bulk density and contain fewer large minerals, which we interpret to be indicative of sediment reworking over time. Two months of monitoring data recorded during summer 2021 indicate that the 60-year-old sediments are stratified showing more spatially consistent changes in electrical resistivity, whereas the younger sediments show a more irregular structure, with consequences on heat and moisture conductibility. Furthermore, our sensors reveal that young sediments have a higher moisture content, but a lower moisture content variability

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Measurement of forward charged hadron flow harmonics in peripheral PbPb collisions at √sNN = 5.02 TeV with the LHCb detector

Flow harmonic coefficients, v n , which are the key to studying the hydrodynamics of the quark-gluon plasma (QGP) created in heavy-ion collisions, have been measured in various collision systems and kinematic regions and using various particle species. The study of flow harmonics in a wide pseudorapidity range is particularly valuable to understand the temperature dependence of the shear viscosity to entropy density ratio of the QGP. This paper presents the first LHCb results of the second- and the third-order flow harmonic coefficients of charged hadrons as a function of transverse momentum in the forward region, corresponding to pseudorapidities between 2.0 and 4.9, using the data collected from PbPb collisions in 2018 at a center-of-mass energy of 5.02 TeV . The coefficients measured using the two-particle angular correlation analysis method are smaller than the central-pseudorapidity measurements at ALICE and ATLAS from the same collision system but share similar features

Nuclear Magnetic Resonance Spectroscopy. Conformational Equilibria and Rates of Conformational Interconversion of Halogenated Ethanes

The relative ground-state energies of the rotational isomers of some halogenated ethanes and the rates and barriers to interconversions of these isomers have been determined by nuclear magnetic resonance spectroscopy. In the ethanes studied in this research, those with a single fluorine were found to have the ^(19)F resonance of the least populated conformation at highest field, while that of the most populated conformation was found at the lowest field. All three barriers for interconversion could be determined for the ethanes substituted so as to give three distinguishable conformations. For these cases it was found that the highest barrier separates the two least populated conformations and the lowest barrier separates the most stable conformations. The substances for which complete nmr line-shape analysis have given the equilibrium constants, rates, and barriers for internal rotation include 1,1,2-tribromo-1,2-dichloro-2-fluoroethane, 1,1- dibromo-1,2,2-trichloro-2-fluoroethane, 1-bromo-1,1,2,2-tetrachloro-2-fluoroethane, 1,1,2,2-tetrabromo-1-chloro-2-fluoroethane, 1,2-dibromo-1,1,2-trichloro-2-fluoroethane, 1,1,2-tribromo-1-chloro-2-fluoroethane, 1-bromo-l,1,2-trichloro-2-fluoroethanaen,d 1,2-dibromo-1,1,24richloro- 3,3,3-trifluoropropane. For those ethanes carrying five halogens other than fluorine, the barriers (to rotation) range from 13.2 to 14.8 kcal/mol, while for those with four halogens other than fluorine, the barriers range from 9.0 to 10.2 kcal/mol. The ground-state energy differences for all of the ethanes studied did not exceed 0.3 kcal/mol

Relationship of molecular structure to in vivo scintigraphic distribution of carbon-11-labeled compounds. 4. Carbon-11-labeled mandelonitriles, mandelic acids and their esters

¹¹C-Labeled HCN was collected in water containing carrier KCN following bombardment of 99% N₂-1% H₂ with 22 MeV protons. ¹¹C-Labeled mandelonitrile and p-methoxy-, p-hydroxy-, and 3,4-dihydroxymandelonitrile were synthesized from K¹¹CN and the corresponding benzaldehyde. The initial distribution of ¹¹C activity of these nitriles in dogs was primarily in the region of the heart, liver, and kidneys followed by rapid redistribution to the parotids and stomach with the [¹¹C]hydroxymandelonitriles. ¹¹C-Labeled mandelic acid and m-methyl-, o-chloro-, and p-chloromandelic acid were synthesized from the corresponding [¹¹C]mandelonitrile. Serial scintigraphy of ¹¹C activity of these mandelic acids in dogs showed progressive renal excretion with accumulation of activity in the bladder. ¹¹C-Labeled ethyl and benzyl mandelate were synthesized from [¹¹C]mandelic acid. These esters showed initial accumulation of activity in the lungs with eventual excretion by the kidneys

Relationship of molecular structure to in vivo scintigraphic distribution of carbon-11-labeled compounds. 4. Carbon-11-labeled mandelonitriles, mandelic acids and their esters

¹¹C-Labeled HCN was collected in water containing carrier KCN following bombardment of 99% N₂-1% H₂ with 22 MeV protons. ¹¹C-Labeled mandelonitrile and p-methoxy-, p-hydroxy-, and 3,4-dihydroxymandelonitrile were synthesized from K¹¹CN and the corresponding benzaldehyde. The initial distribution of ¹¹C activity of these nitriles in dogs was primarily in the region of the heart, liver, and kidneys followed by rapid redistribution to the parotids and stomach with the [¹¹C]hydroxymandelonitriles. ¹¹C-Labeled mandelic acid and m-methyl-, o-chloro-, and p-chloromandelic acid were synthesized from the corresponding [¹¹C]mandelonitrile. Serial scintigraphy of ¹¹C activity of these mandelic acids in dogs showed progressive renal excretion with accumulation of activity in the bladder. ¹¹C-Labeled ethyl and benzyl mandelate were synthesized from [¹¹C]mandelic acid. These esters showed initial accumulation of activity in the lungs with eventual excretion by the kidneys