Induction of T Cell Senescence by Cytokine Induced Bystander Activation

As people around the world continue to live longer, maintaining a good quality of life is of increasing importance. The COVID-19 pandemic revealed that the elderly are disproportionally vulnerable to infectious diseases and Immunosenescence plays a critical role in that. An ageing immune system influences the conventional activity of T cells which are at the forefront of eliminating harmful foreign antigens. With ageing, unconventional end-stage T cells, that exhibit a senescent phenotype, amass. These senescent T cells deviate from T cell receptor (TCR) signaling toward natural killer (NK) activity. The transition toward innate immune cell function from these adaptor T cells impacts antigen specificity, contributing to increased susceptibility of infection in the elderly. The mechanism by which senescent T cells arise remains largely unclear however in this review we investigate the part that bystander activation plays in driving the change in function of T cells with age. Cytokine-induced bystander activation may offer a plausible explanation for the induction of NK-like activity and senescence in T cells. Further understanding of these specific NK-like senescent T cells allows us to identify the benefits and detriments of these cells in health and disease which can be utilized or regulated, respectively. This review discusses the dynamic of senescent T cells in adopting NK-like T cells and the implications that has in an infectious disease context, predominately in the elderly

Stabilization of a highly expansive soil using waste-tire-derived aggregates and lime treatment

This study investigates the combined efficacy of waste-tire-derived aggregate (TDA) materials and hydrated lime on the compactability, compressive strength and swelling potential of a highly expansive soil from South Australia. A total of 21 mix-designs, covering a comprehensive range of soil–TDA–lime combinations, were examined through standard Proctor compaction, unconfined compressive strength (UCS) and oedometer swell tests. The mobilized UCS exhibited a ‘rise–fall’ behavior, peaking at 5% TDA content and subsequently decreasing (monotonically) for higher inclusions of TDA. Increasing the TDA mean particle size (from 1.67 to 3.34 mm) also contributed positively to the UCS development. Addition of TDA to the soil/soil–lime-blends produced notable reductions in the swelling potential; the reduction was primarily governed by higher TDA contents, and, to a lesser degree, for larger TDA mean particle sizes. However, the role of TDA particle size in reducing swelling was found to be more significant than that of enhancing the UCS. As expected, lime treatment of the soil–TDA blends provided major further improvements to the UCS and swelling potential reduction; the achieved UCS improvements being positively proportional to the lime content and curing time. In view of the experimental results, soil–lime blends containing TDA to soil–lime mass ratios of up to 10% (preferably employing coarse-sand-sized equivalent TDA) can be deemed as suitable choices (capable of adequately mitigating the swelling potential, while simultaneously enhancing the UCS). © 2022 The Author

The propensity to cycle tool: An open source online system for sustainable transport planning

© 2016 Robin Lovelace, Anna Goodman, Rachel Aldred, Nikolai Berkoff, Ali Abbas, and James Woodcock.Getting people cycling is an increasingly common objective in transport planning institutions worldwide. A growing evidence base indicates that high quality infrastructure can boost local cycling rates. Yet for infrastructure and other cycling measures to be effective, it is important to intervene in the right places, such as along ‘desire lines’ of high latent demand. This creates the need for tools and methods to help answer the question ‘where to build?’. Following a brief review of the policy and research context related to this question, this paper describes the design, features and potential applications of such a tool. The Propensity to Cycle Tool (PCT) is an online, interactive planning support system that was initially developed to explore and map cycling potential across England (see www.pct.bike). Based on origin-destination data it models cycling levels at area, desire line, route and route network levels, for current levels of cycling, and for scenario-based ‘cycling futures.’ Four scenarios are presented, including ‘Go Dutch’ and ‘Ebikes,’ which explore what would happen if English people had the same propensity to cycle as Dutch people and the potential impact of electric cycles on cycling uptake. The cost effectiveness of investment depends not only on the number of additional trips cycled, but on wider impacts such as health and carbon benefits. The PCT reports these at area, desire line, and route level for each scenario. The PCT is open source, facilitating the creation of scenarios and deployment in new contexts. We conclude that the PCT illustrates the potential of online tools to inform transport decisions and raises the wider issue of how models should be used in transport planning.The work presented was funded by the Department for Transport (contract no. RM5019SO7766: “Provision of Research Programme into Cycling: Propensity to Cycle”), with contract facilitation and project management by Brook Lyndhurst in Phase 1, and by Atkins in Phase 2. RL’s contribution was supported by the Consumer Data Research Centre (ESRC grant number ES/L011891/1). JW’s contribution was supported by an MRC Population Health Scientist Fellowship. JW’s and AA’s contributions were supported by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence funded by the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research (NIHR), and the Wellcome Trust. AG’s contribution was supported by an NIHR post-doctoral fellowship. The views reported in this paper are those of the authors and do not necessarily represent those of the DfT, Brook Lyndhurst, Atkins the NIHR, the NHS or the Department for Health

Improved shear strength performance of compacted rubberized clays treated with sodium alginate biopolymer

This study examines the potential use of sodium alginate (SA) biopolymer as an environmentally sustainable agent for the stabilization of rubberized soil blends prepared using a high plasticity clay soil and tire-derived ground rubber (GR). The experimental program consisted of uniaxial compression and scanning electron microscopy (SEM) tests; the former was performed on three soil–GR blends (with GR-to-soil mass ratios of 0%, 5% and 10%) compacted (and cured for 1, 4, 7 and 14 d) employing distilled water and three SA solutions—prepared at SA-to-water (mass-tovolume) dosage ratios of 5, 10 and 15 g/L—as the compaction liquid. For any given GR content, the greater the SA dosage and/or the longer the curing duration, the higher the uniaxial compressive strength (UCS), with only minor added benefits beyond seven days of curing. This behaviour was attributed to the formation and propagation of so-called “cationic bridges” (developed as a result of a “Ca2+/Mg2

High yield synthesis of graphene quantum dots from biomass waste as a highly selective probe for Fe3+ sensing

Graphene quantum dots (GQDs), a novel type of zero-dimensional fluorescent materials, have gained considerable attention owing to their unique optical properties, size and quantum confinement. However, their high cost and low yield remain open challenges for practical applications. In this work, a low cost, green and renewable biomass resource is utilised for the high yield synthesis of GQDs via microwave treatment. The synthesis approach involves oxidative cutting of short range ordered carbon derived from pyrolysis of biomass waste. The GQDs are successfully synthesised with a high yield of over 84%, the highest value reported to date for biomass derived GQDs. As prepared GQDs are highly hydrophilic and exhibit unique excitation independent photoluminescence emission, attributed to their single-emission fluorescence centre. As prepared GQDs are further modified by simple hydrothermal treatment and exhibit pronounced optical properties with a high quantum yield of 0.23. These modified GQDs are used for the highly selective and sensitive sensing of ferric ions (Fe3+). A sensitive sensor is prepared for the selective detection of Fe3+ ions with a detection limit of as low as 2.5 × 10–6 M. The utilisation of renewable resource along with facile microwave treatment paves the way to sustainable, high yield and cost-effective synthesis of GQDs for practical applications

Effect of simulated acid rain on CO₂, CH₄ and N₂O fluxes and rice productivity in a subtropical Chinese paddy field

The need of more food production, an increase in acidic deposition and the large capacity of paddy to emit greenhouse gases all coincide in several areas of China. Studying the effects of acid rain on the emission of greenhouse gases and the productivity of rice paddies are thus important, because these effects are currently unknown. We conducted a field experiment for two rice croppings (early and late paddies independent experiment) to determine the effects of simulated acid rain (control, normal rain, and treatments with rain at pH of 4.5, 3.5 and 2.5) on the fluxes of CO₂, CH₄ and N₂O and on rice productivity in subtropical China. Total CO₂ fluxes at pHs of 4.5, 3.5 and 2.5 were 10.3, 9.7 and 3.2% lower in the early paddy and 28.3, 14.8 and 6.8% lower in the late paddy, respectively, than the control. These differences from the control were significant for pH 3.5 and 4.5. Total CH₄ fluxes at pHs of 4.5, 3.5 and 2.5 were 50.4, 32.9 and 25.2% lower in the early paddy, respectively, than the control. pH had no significant effect on CH₄ flux in the late paddy or for total (early + late) emissions. N₂O flux was significantly higher at pH 2.5 than 3.5 and 4.5 but did not differ significantly from the flux in the control. Global-warming potentials (GWPs) were lower than the control at pH 3.5 and 4.5 but not 2.5, whereas rice yield was not appreciably affected by pH. Acid rain (between 3.5 and 4.5) may thus significantly affect greenhouse gases emissions by altering soil properties such as pH and nutrient pools, whereas highly acidic rain (pH 2.5) could increase GWPs (but not significantly), probably partially due to an increase in the production of plant litter

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction

Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis

OBJECTIVES: The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF). METHODS: In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end-to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables, and lung function tests. Univariable and multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern, and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT. RESULTS: No significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced intersegmental tapering, and increased segmental tortuosity associated with increased risk of death. On multivariable Cox analyses (adjusted using FVC), intersegmental tapering (hazard ratio (HR) = 0.75, 95% CI = 0.66-0.85, p < 0.001) and segmental tortuosity (HR = 1.74, 95% CI = 1.22-2.47, p = 0.002) independently associated with mortality. Results were maintained with adjustment using DLco. CONCLUSIONS: AirQuant generated measures of intersegmental tapering and segmental tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value. CLINICAL RELEVANCE STATEMENT: Quantitative measurements of intersegmental tapering and segmental tortuosity, in proximal (second to sixth) generation airway segments, independently associate with mortality in IPF. Automated airway analysis can estimate disease severity, which in IPF is not restricted to the distal airway tree. KEY POINTS: • AirQuant generates measures of intersegmental tapering and segmental tortuosity. • Automated airway quantification associates with mortality in IPF independent of established measures of disease severity. • Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF

Deviation from Tri-Bimaximal Mixing and Large Reactor Mixing Angle

Recent observations for a non-zero $\theta_{13}$ have come from various experiments. We study a model of lepton mixing with a 2-3 flavor symmetry to accommodate the sizable $\theta_{13}$ measurement. In this work, we derive deviations from the tri-bimaximal (TBM) pattern arising from breaking the flavor symmetry in the neutrino sector, while the charged leptons contribution has been discussed in a previous work. Contributions from both sectors towards accommodating the non-zero $\theta_{13}$ measurement are presented.Comment: 25 pages, 12 figures. arXiv admin note: text overlap with arXiv:1109.232