Characterization and Evaluation of Methane Oxidation Catalysts for Dual-Fuel Diesel and Natural Gas Engines

The UK has incentivized the use of natural gas in heavy goods vehicles (HGVs) by converting to dual-fuel (DF) diesel-natural gas systems to reduce noxious and greenhouse gas emissions. Laboratory and on-road measurements of DF vehicles have demonstrated a decrease in CO$_2$ emissions relative to diesel, but there is an increase in greenhouse gas (CO$_2$e) emissions because of unburned methane. Decreasing tailpipe emissions of methane via after-treatment devices in lean-burn compression ignition engines is a challenge because of low exhaust temperatures (~400 °C) and the presence of water vapor. In this study, six commercially available methane oxidation catalysts (MOCs) were tested for their application in DF HGV vehicles. Each MOC was characterized in terms of the catalyst platinum group metal (PGM) loading (both Pd and Pt), particle size, catalytic surface area, and Pd:Pt ratio. In addition, the washcoat surface area, pore volume, and pore size were evaluated. The MOC conversion efficiency was evaluated in controlled methane-oxidation experiments with varying temperatures, flow rates, and gas compositions. Characteristic-conversion efficiency correlations demonstrate that the influential MOC characteristics were PGM loading (both Pd and Pt), Pd:Pt ratio, washcoat surface area, and washcoat pore volume. With 90 % methane oxidation at less than 400 °C in DF HGV exhaust conditions, sample 1 had the highest conversion efficiency because of a high PGM loading (330 g/ft$^3$, 12,000 g/m$^3$), a 5.9 Pd:Pt ratio, a high alumina washcoat surface area of 20 m$^2$/cm$^3$, and 74-mm$^3$/cm$^3$ pore volume. Additional studies showed increased MOC conversion efficiency with decreasing gas hourly space velocities (GHSVs) and increasing methane concentrations.We acknowledge support from the UK Engineering and Physical Sciences Research Council (EP/K00915X/1), the UK Department for Transport, the Office for Low Emission Vehicles and Innovate UK (project reference 400266), and the industrial partners of the Centre for Sustainable Road Freight. GreenUrban Technologies Ltd. (3) and Prins Autogas UK Ltd. (1) provided the samples for testing in this study

Functional and Molecular Analysis of Human Osteoarthritic Chondrocytes Treated with Bone Marrow-Derived MSC-EVs

\ua9 2024 by the authors.Osteoarthritis (OA) is a degenerative joint disease, causing impaired mobility. There are currently no effective therapies other than palliative treatment. Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) have shown promise in attenuating OA progression, promoting chondral regeneration, and modulating joint inflammation. However, the precise molecular mechanism of action driving their beneficial effects has not been fully elucidated. In this study, we analyzed MSC-EV-treated human OA chondrocytes (OACs) to assess viability, proliferation, migration, cytokine and catabolic protein expression, and microRNA and mRNA profiles. We observed that MSC-EV-treated OACs displayed increased metabolic activity, proliferation, and migration compared to the controls. They produced decreased proinflammatory (Il-8 and IFN-γ) and increased anti-inflammatory (IL-13) cytokines, and lower levels of MMP13 protein coupled with reduced expression of MMP13 mRNA, as well as negative microRNA regulators of chondrogenesis (miR-145-5p and miR-21-5p). In 3D models, MSC-EV-treated OACs exhibited enhanced chondrogenesis-promoting features (elevated sGAG, ACAN, and aggrecan). MSC-EV treatment also reversed the pathological impact of IL-1β on chondrogenic gene expression and extracellular matrix component (ECM) production. Finally, MSC-EV-treated OACs demonstrated the enhanced expression of genes associated with cartilage function, collagen biosynthesis, and ECM organization and exhibited a signature of 24 differentially expressed microRNAs, associated with chondrogenesis-associated pathways and ECM interactions. In conclusion, our data provide new insights on the potential mechanism of action of MSC-EVs as a treatment option for early-stage OA, including transcriptomic analysis of MSC-EV-treated OA, which may pave the way for more targeted novel therapeutics

Tissue-specific expression Patterns of Microrna during acute graft-versus-host Disease in the rat

MicroRNAs (miRNA) have emerged as central regulators of diverse biological processes and contribute to driving pathology in several diseases. Acute graft-versus-host disease (aGvHD) represents a major complication after allogeneic hematopoietic stem cell transplantation, caused by alloreactive donor T cells attacking host tissues leading to inflammation and tissue destruction. Changes in miRNA expression patterns occur during aGvHD, and we hypothesized that we could identify miRNA signatures in target tissues of aGvHD that may potentially help understand the underlying molecular pathology of the disease. We utilized a rat model of aGvHD with transplantation of fully MHC-mismatched T cell depleted bone marrow, followed by infusion of donor T cells. The expression pattern of 423 rat miRNAs was investigated in skin, gut, and lung tissues and intestinal T cells with the NanoString hybridization platform, in combination with validation by quantitative PCR. MHC-matched transplanted rats were included as controls. In the skin, upregulation of miR-34b and downregulation of miR-326 was observed, while in the intestines, we detected downregulation of miR-743b and a trend toward downregulation of miR-345-5p. Thus, tissue-specific expression patterns of miRNAs were observed. Neither miR-326 nor miR-743b has previously been associated with aGvHD. Moreover, we identified upregulation of miR-146a and miR-155 in skin tissue of rats suffering from aGvHD. Analysis of intestinal T cells indicated 23 miRNAs differentially regulated between aGvHD and controls. Two of these miRNAs were differentially expressed either in skin (miR-326) or in intestinal (miR-345-5p) tissue. Comparison of intestinal and peripheral blood T cells indicated common dysregulated expression of miR-99a, miR-223, miR-326, and miR-345-5p. Analysis of predicted gene targets for these miRNAs indicated potential targeting of an inflammatory network both in skin and in the intestines that may further regulate inflammatory cytokine production. In conclusion, comprehensive miRNA profiling in rats suffering from aGvHD demonstrate tissue-specific differences in the expression patterns of miRNA that may not be detected by profiling of peripheral blood T cells alone. These tissue-specific miRNAs may contribute to distinct pathologic mechanisms and could represent potential targets for therapy

Expression Profiling of Major Histocompatibility and Natural Killer Complex Genes Reveals Candidates for Controlling Risk of Graft versus Host Disease

Background: The major histocompatibility complex (MHC) is the most important genomic region that contributes to the risk of graft versus host disease (GVHD) after haematopoietic stem cell transplantation. Matching of MHC class I and II genes is essential for the success of transplantation. However, the MHC contains additional genes that also contribute to the risk of developing acute GVHD. It is difficult to identify these genes by genetic association studies alone due to linkage disequilibrium in this region. Therefore, we aimed to identify MHC genes and other genes involved in the pathophysiology of GVHD by mRNA expression profiling. Methodology/Principal Findings: To reduce the complexity of the task, we used genetically well-defined rat inbred strains and a rat skin explant assay, an in-vitro-model of the graft versus host reaction (GVHR), to analyze the expression of MHC, natural killer complex (NKC), and other genes in cutaneous GVHR. We observed a statistically significant and strong up or down regulation of 11 MHC, 6 NKC, and 168 genes encoded in other genomic regions, i.e. 4.9%, 14.0%, and 2.6% of the tested genes respectively. The regulation of 7 selected MHC and 3 NKC genes was confirmed by quantitative real-time PCR and in independent skin explant assays. In addition, similar regulations of most of the selected genes were observed in GVHD-affected skin lesions of transplanted rats and in human skin explant assays. Conclusions/Significance: We identified rat and human MHC and NKC genes that are regulated during GVHR in skin explant assays and could therefore serve as biomarkers for GVHD. Several of the respective human genes, including HLA-DMB, C2, AIF1, SPR1, UBD, and OLR1, are polymorphic. These candidates may therefore contribute to the genetic risk of GVHD in patients

Childhood solid tumours in relation to infections in the community in Cumbria during pregnancy and around thetime of birth

In a retrospective cohort study of all 99 976 live births in Cumbria, 1975–1992, we investigated whether higher levels of community infections during the mother's pregnancy and in early life were risk factors for solid tumours (brain/spinal and other tumours), diagnosed 1975–1993 under age 15 years. Logistic regression was used to relate risk to incidence of community infections in three prenatal and two postnatal quarters. There was an increased risk of brain/spinal tumours among children exposed around or soon after birth to higher levels of community infections, in particular measles (OR for trend=2.1, 95%CI : 1.3–3.6, P=0.008) and influenza (OR for exposure=3.3, 95%CI : 1.5–7.4, P=0.005). There was some evidence of an association between exposure to infections around and soon after birth and risk of other tumours, but this may have been a chance finding. The findings are consistent with other recent epidemiological studies suggesting brain tumours may be associated with perinatal exposure to infections

BSE can propagate in sheep co-infected or pre-infected with scrapie

To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform encephalopathy (BSE) and scrapie. The bovine BSE agent was inoculated subcutaneously into sheep with ARQ/ARQ or VRQ/ARQ PRNP genotypes either at the same time as subcutaneous challenge with scrapie, or three months later. In addition, VRQ/VRQ sheep naturally infected with scrapie after being born into a scrapie-affected flock were challenged subcutaneously with BSE at eight or twenty one months-of-age. Sheep were analysed by incubation period/attack rate, and western blot of brain tissue determined the presence of BSE or scrapie-like PrP Sc. Serial protein misfolding cyclic amplification (sPMCA) that can detect very low levels of BSE in the presence of an excess of scrapie agent was also applied to brain and lymphoreticular tissue. For VRQ/ARQ sheep challenged with mixed infections, scrapie-like incubation periods were produced, and no BSE agent was detected. However, whilst ARQ/ARQ sheep developed disease with BSE-like incubation periods, some animals had a dominant scrapie western blot phenotype in brain, but BSE was detected in these sheep by sPMCA. In addition, VRQ/VRQ animals challenged with BSE after natural exposure to scrapie had scrapie-like incubation periods and dominant scrapie PrP Sc in brain, but one sheep had BSE detectable by sPMCA in the brain. Overall, the study demonstrates for the first time that for scrapie/BSE mixed infections, VRQ/ARQ sheep with experimental scrapie did not propagate BSE but VRQ/VRQ sheep with natural scrapie could propagate low levels of BSE, and whilst BSE readily propagated in ARQ/ARQ sheep it was not always the dominant PrP Sc strain in brain tissue. Indeed, for several animals, a dominant scrapie biochemical phenotype in brain did not preclude the presence of BSE prion

CANDELSz7: A large spectroscopic survey of CANDELS galaxies in the reionization epoch

We present the results of CANDELSz7, an ESO large program aimed at confirming spectroscopically a homogeneous sample of z~6 and z~7 star forming galaxies. The candidates were selected in the GOODS-South, UDS and COSMOS fields using the official CANDELS catalogs based on H160-band detections. Standard color criteria, which were tailored depending on the ancillary multi-wavelength data available for each field, were applied to select more than 160 candidate galaxies at z~6 and z~7. Deep medium resolution FORS2 spectroscopic observations were then conducted with integration times ranging from 12 to 20 hours, to reach a Lyalpha flux limit of approximately 1-3x 10-18 erg/s/cm^2 at 3sigma. For about 40% of the galaxies we could determine a spectroscopic redshift, mainly through the detection of a single emission line that we interpret as Lyalpha emission, or for some of the brightest objects (H160< 25.5) from the presence of faint continuum and sharp drop that we interpret as a Lyman break. In this paper we present the redshifts and main properties of 65 newly confirmed high redshift galaxies. Adding previous proprietary and archival data we assemble a sample of ~260 galaxies that we use to explore the evolution of the Lyalpha fraction in Lyman break galaxies and the change in the shape of the emission line between z~6 and z~7. We also discuss the accuracy of the CANDELS photometric redshifts in this redshift range.STFC ER

Tailored education for older patients to facilitate engagement in falls prevention strategies after hospital discharge—A pilot randomized controlled trial

Background The aims of the study were to evaluate the effect of providing tailored falls prevention education in hospital on: i) engagement in targeted falls prevention behaviors in the month after discharge: ii) patients’ self-perceived risk and knowledge about falls and falls prevention strategies after receiving the education. Methods A pilot randomized controlled trial (n = 50): baseline and outcome assessments conducted by blinded researchers. Participants: hospital inpatients 60 years or older, discharged to the community. Participants were randomized into two groups. The intervention was a tailored education package consisting of multimedia falls prevention information with trained health professional follow-up, delivered in addition to usual care. Outcome measures were engagement in falls prevention behaviors in the month after discharge measured at one month after discharge with a structured survey, and participants’ knowledge, confidence and motivation levels before and after receiving the education. The feasibility of providing the intervention was examined and falls outcomes (falls, fall-related injuries) were also collected. Results Forty-eight patients (98%) provided follow-up data. The complete package was provided to 21 (84%) intervention group participants. Participants in the intervention group were significantly more likely to plan how to safely restart functional activities [Adjusted odds ratio 3.80, 95% CI (1.07, 13.52), p = 0.04] and more likely to complete other targeted behaviors such as completing their own home exercise program [Adjusted odds ratio 2.76, 95% CI (0.72, 10.50), p = 0.14] than the control group. The intervention group was significantly more knowledgeable, confident and motivated to engage in falls prevention strategies after receiving the education than the control group. There were 23 falls (n = 5 intervention; n = 18 control) and falls rates were 5.4/1000 patient days (intervention); 18.7/1000 patient days (control). Conclusion This tailored education was received positively by older people, resulted in increased engagement in falls prevention strategies after discharge and is feasible to deliver to older hospital patients. Trial registration The study was registered with the Australian New Zealand Clinical Trials Registry; ACTRN12611000963921 on 8th November 2011

Exotendons for assistance of human locomotion

BACKGROUND: Powered robotic exoskeletons for assistance of human locomotion are currently under development for military and medical applications. The energy requirements for such devices are excessive, and this has become a major obstacle for practical applications. Legged locomotion in many animals, however, is very energy efficient. We propose that poly-articular elastic mechanisms are a major contributor to the economy of locomotion in such specialized animals. Consequently, it should be possible to design unpowered assistive devices that make effective use of similar mechanisms. METHODS: A passive assistive technology is presented, based on long elastic cords attached to an exoskeleton and guided by pulleys placed at the joints. A general optimization procedure is described for finding the best geometrical arrangement of such "exotendons" for assisting a specific movement. Optimality is defined either as minimal residual joint moment or as minimal residual joint power. Four specific exotendon systems with increasing complexity are considered. Representative human gait data were used to optimize each of these four systems to achieve maximal assistance for normal walking. RESULTS: The most complex exotendon system, with twelve pulleys per limb, was able to reduce the joint moments required for normal walking by 71% and joint power by 74%. A simpler system, with only three pulleys per limb, could reduce joint moments by 46% and joint power by 47%. CONCLUSION: It is concluded that unpowered passive elastic devices can substantially reduce the muscle forces and the metabolic energy needed for walking, without requiring a change in movement. When optimally designed, such devices may allow independent locomotion in patients with large deficits in muscle function