Buried pipelines with bends:Analytical verification against permanent ground displacements

Available analytical methodologies for the strength verification of buried pipelines against large permanent ground displacements (PGDs) apply only to straight pipeline segments. Hence, a new methodology is proposed herein for the analytical computation of pipeline strains in bends of arbitrary angle and radius of curvature, located outside the PGD high-curvature zone but within the pipelineâ s unanchored length. The methodology is based on the equivalent-linear analysis of the bend, assuming that it will perform as an elastic arched beam subjected to uniformly distributed ultimate axial and transverse horizontal soil reactions. The end of the bend towards the PGD zone is subjected to an axial displacement, calculated on the basis of overall displacement compatibility along the pipeline, while the other end is restrained by the unanchored pipeline segment beyond the bend. Using this approach, the maximum axial force at the vicinity of the PGD zone can be also calculated and consequently used for the estimation of the corresponding pipeline strains with any of the available numerical or analytical methodologies for straight pipeline segments. Parametric non-linear finite element analyses are performed in order to verify the analytical methodology and also derive conclusions of practical interest regarding the effect of bends on pipeline design.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Biocatalysis, Enzyme Engineering and Biotechnology

Enzymes are biocatalysts evolved in nature to achieve the speed and coordination of nearly all the chemical reactions that define cellular metabolism necessary to develop and maintain life. The application of biocatalysis is growing rapidly, since enzymes offer potential for many exciting applications in industry. The advent of whole genome sequencing projects enabled new approaches for biocatalyst development, based on specialised methods for enzyme heterologous expression and engineering. The engineering of enzymes with altered activity, specificity and stability, using sitedirected mutagenesis and directed evolution techniques are now well established. Over the last decade, enzyme immobilisation has become important in industry. New methods and techniques for enzyme immobilisation allow for the reuse of the catalysts and the development of efficient biotechnological processes. This chapter reviews advances in enzyme technology as well as in the techniques and strategies used for enzyme production, engineering and immobilisation and discuss their advantages and disadvantages

Monte-Carlo dosimetry on a realistic cell monolayer geometry exposed to alpha particles

The energy and specific energy absorbed in the main cell compartments (nucleus and cytoplasm) in typical radiobiology experiments are usually estimated by calculations as they are not accessible for a direct measurement. In most of the work, the cell geometry is modelled using the combination of simple mathematical volumes. We propose a method based on high resolution confocal imaging and ion beam analysis (IBA) in order to import realistic cell nuclei geometries in Monte-Carlo simulations and thus take into account the variety of different geometries encountered in a typical cell population. Seventy-six cell nuclei have been imaged using confocal microscopy and their chemical composition has been measured using IBA. A cellular phantom was created from these data using the ImageJ image analysis software and imported in the Geant4 Monte-Carlo simulation toolkit. Total energy and specific energy distributions in the 76 cell nuclei have been calculated for two types of irradiation protocols: a 3 MeV alpha particle microbeam used for targeted irradiation and a 239Pu alpha source used for large angle random irradiation. Qualitative images of the energy deposited along the particle tracks have been produced and show good agreement with images of DNA double strand break signalling proteins obtained experimentally. The methodology presented in this paper provides microdosimetric quantities calculated from realistic cellular volumes. It is based on open-source oriented software that is publicly available

Tri-Resonant Leptogenesis in a Seesaw Extension of the Standard Model

We study a class of leptogenesis models where the light neutrinos acquire their observed small masses by a symmetry-motivated construction. This class of models may naturally include three nearly degenerate heavy Majorana neutrinos that can strongly mix with one another and have mass differences comparable to their decay widths. We find that such a tri-resonant heavy neutrino system can lead to leptonic CP asymmetries which are further enhanced than those obtained in the usual bi-resonant approximation. Moreover, we solve the Boltzmann equations by paying special attention to the temperature dependence of the relativistic degrees of freedom of the plasma. The latter results in significant corrections to the evolution equations for the heavy neutrinos and the lepton asymmetry that have been previously ignored in the literature. We show the importance of these corrections to accurately describe the dynamical evolution of the baryon-to-photon ratio $\eta_B$ for heavy neutrino masses at and below $100$ GeV, and demonstrate that successful leptogenesis at lower masses can be significantly affected by the variation of the relativistic dofs. The parameter space for the leptogenesis model is discussed, and it could be probed in future experimental facilities searching for charged lepton flavour violation and heavy neutrinos in future $Z$-boson factories.Comment: 42 pages, 10 figures, additional references included, inclusion of additional clarifying comments, to appear in JHE

Tri-Resonant Leptogenesis

We present a class of leptogenesis models where the light neutrinos acquire their observed mass through a symmetry-motivated construction. We consider an extension of the Standard Model, which includes three singlet neutrinos which have mass splittings comparable to their decay widths. We show that this tri-resonant structure leads to an appreciable increase in the observed CP asymmetry over that found previously in typical bi-resonant models. To analyse such tri-resonant scenarios, we solve a set of coupled Boltzmann equations, crucially preserving the variations in the relativistic degrees of freedom. We highlight the fact that small variations at high temperatures can have major implications for the evolution of the baryon asymmetry when the singlet neutrino mass scale is below $100$ GeV. We then illustrate how this variation can significantly affect the ability to find successful leptogenesis at these low masses. Finally, the parameter space for viable leptogenesis is delineated, and comparisons are made with current and future experiments.Comment: 16 pages, 5 figures, conference proceedings for Corfu Summer Institute 2022, School and Workshops on Elementary Particle Physics and Gravity, August 28 - September 8, 2022, Corfu, Greec

The interferon receptor-1 promoter polymorphisms affect the outcome of Caucasians with HBeAg-negative chronic HBV infection

The outcome of HBeAg-negative chronic hepatitis B virus (HBV) patients who may remain in the inactive carrier state (IC) or progress to HBeAg-negative chronic hepatitis B may be affected by the host genetic profile. Genetic polymorphisms within not only the promoter but also the coding sequence of the interferon receptor 1 (INFAR1) gene have been associated with susceptibility to chronic HBV infection, but their role on the outcomes of HBeAg-negative patients has not been evaluated. We examined the association of INFAR1 promoter polymorphisms with the phase of chronic HBV infection in a demographically characterized Caucasian cohort of 183 consecutive HBeAg-negative chronic HBV patients.Using a combination of conventional and allele-specific polymerase chain reactions, bidirectional sequencing and DNA-fragment analysis, we performed typing of three Single Nucleotide Polymorphisms (SNPs -568G/C, -408C/T, -3C/T) and one Variable Number Tandem Repeat [VNTR -77(GT)n] within the INFR1 promoter sequence.The genetic polymorphisms examined were found to be associated with the phase of HBeAg-negative chronic HBV patients. Using a multiple logistic regression model adjusting for age, gender and origin of the individuals, we found that patients with linked genotypes -408CT_-3CT were more likely to be ICs (OR = 2.42 vs. CC, P = 0.036). Also, given the partial linkage between SNP -568G/C and VNTR -77(GT)n, we found that linked genotypes -77(GT)n ≤ 8/≤8_-568GC and -77(GT)n ≤ 8/≤8_-568CC were detected more frequently among ICs (OR = 11.69, P = 0.005 and OR = 7.56, P = 0.001 vs. -77(GT)n >8/>8_-568GG respectively).These findings suggest that these genetic variations represent important factors associated with the clinical phase of HBeAg-negative chronic HBV infection

Reducing HIV infection in people who inject drugs is impossible without targeting recently-infected subjects.

Objective Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient. Design Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID. Method We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID. Results In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post–first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective. Conclusion As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID.Growing PWID populations in the developing world,where primary prevention is scarce, constitutes a public health time bomb

Integral abutment bridges: Investigation of seismic soil-structure interaction effects by shaking table testing

In recent years there has been renewed interest on integral abutment bridges (IABs), mainly due to their low construction and maintenance cost. Owing to the monolithic connection between deck and abutments, there is strong soil-structure interaction between the bridge and the backfill under both thermal action and earthquake shaking. Although some of the regions where IABs are adopted qualify as highly seismic, there is limited knowledge as to their dynamic behaviour and vulnerability under strong ground shaking. To develop a better understanding on the seismic behaviour of IABs, an extensive experimental campaign involving over 75 shaking table tests and 4800 time histories of recorded data, was carried out at EQUALS Laboratory, University of Bristol, under the auspices of EU-sponsored SERA project (Seismology and Earthquake Engineering Research Infrastructure Alliance for Europe). The tests were conducted on a 5 m long shear stack mounted on a 3 m × 3 m 6-DOF earthquake simulator, focusing on interaction effects between a scaled bridge model, abutments, foundation piles and backfill soil. The study aims at (a) developing new scaling procedures for physical modelling of IABs, (b) investigating experimentally the potential benefits of adding compressible inclusions (CIs) between the abutment and the backfill and (c) exploring the influence of different types of connection between the abutment and the pile foundation. Results indicate that the CI reduces the accelerations on the bridge deck and the settlements in the backfill, while disconnecting piles from the cap decreases bending near the pile head

Human endogenous retrovirus-K HML-2 integration within RASGRF2 is associated with intravenous drug abuse and modulates transcription in a cell-line model

HERV-K HML-2 (HK2) has been proliferating in the germ line of humans at least as recently as 250,000 years ago, with some integrations that remain polymorphic in the modern human population. One of the solitary HK2 LTR polymorphic integrations lies between exons 17 and 18 of RASGRF2, a gene that affects dopaminergic activity and is thus related to addiction. Here we show that this antisense HK2 integration (namely RASGRF2-int) is found more frequently in persons who inject drugs compared with the general population. In a Greek HIV-1–positive population (n = 202), we found RASGRF2-int 2.5 times (14 versus 6%) more frequently in patients infected through i.v. drug use compared with other transmission route controls (P = 0.03). Independently, in a United Kingdom-based hepatitis C virus-positive population (n = 184), we found RASGRF2-int 3.6 times (34 versus 9.5%) more frequently in patients infected during chronic drug abuse compared with controls (P ≺ 0.001). We then tested whether RASGRF2-int could be mechanistically responsible for this association by modulating transcription of RASGRF2. We show that the CRISPR/Cas9-mediated insertion of HK2 in HEK293 cells in the exact RASGRF2 intronic position found in the population resulted in significant transcriptional and phenotypic changes. We also explored mechanistic features of other intronic HK2 integrations and show that HK2 LTRs can be responsible for generation of cis-natural antisense transcripts, which could interfere with the transcription of nearby genes. Our findings suggest that RASGRF2-int is a strong candidate for dopaminergic manipulation, and emphasize the importance of accurate mapping of neglected HERV polymorphisms in human genomic studies