Effects of orally administered Bdellovibrio bacteriovorus on the well-being and Salmonella colonization of young chicks

Bdellovibrio bacteriovorus is a bacterium which preys upon and kills Gram-negative bacteria, including the zoonotic pathogens Escherichia coli and Salmonella. Bdellovibrio has potential as a biocontrol agent, but no reports of it being tested in living animals have been published, and no data on whether Bdellovibrio might spread between animals are available. In this study, we tried to fill this knowledge gap, using B. bacteriovorus HD100 doses in poultry with a normal gut microbiota or predosed with a colonizing Salmonella strain. In both cases, Bdellovibrio was dosed orally along with antacids. After dosing non-Salmonella-infected birds with Bdellovibrio, we measured the health and well-being of the birds and any changes in their gut pathology and culturable microbiota, finding that although a Bdellovibrio dose at 2 days of age altered the overall diversity of the natural gut microbiota in 28-day-old birds, there were no adverse effects on their growth and well-being. Drinking water and fecal matter from the pens in which the birds were housed as groups showed no contamination by Bdellovibrio after dosing. Predatory Bdellovibrio orally administered to birds that had been predosed with a gut-colonizing Salmonella enterica serovar Enteritidis phage type 4 strain (an important zoonotic pathogen) significantly reduced Salmonella numbers in bird gut cecal contents and reduced abnormal cecal morphology, indicating reduced cecal inflammation, compared to the ceca of the untreated controls or a nonpredatory ΔpilA strain, suggesting that these effects were due to predatory action. This work is a first step to applying Bdellovibrio therapeutically for other animal, and possibly human, infections.

Oxygen vacancy formation in CeO2 and Ce1-xZrxO2 solid solutions:electron localization, electrostatic potential and structural relaxation

Ceria (CeO2) and ceria-based composite materials, especially Ce1-xZrxO2 solid solutions, possess a wide range of applications in many important catalytic processes, such as three-way catalysts, owing to their excellent oxygen storage capacity (OSC) through the oxygen vacancy formation and refilling. Much of this activity has focused on the understanding of the electronic and structural properties of defective CeO2 with and without doping, and comprehending the determining factor for oxygen vacancy formation and the rule to tune the formation energy by doping has constituted a central issue in material chemistry related to ceria. However, the calculation on electronic structures and the corresponding relaxation patterns in defective CeO2-x oxides remains at present a challenge in the DFT framework. A pragmatic approach based on density functional theory with the inclusion of on-site Coulomb correction, i.e. the so-called DFT + U technique, has been extensively applied in the majority of recent theoretical investigations. Firstly, we review briefly the latest electronic structure calculations of defective CeO2(111), focusing on the phenomenon of multiple configurations of the localized 4f electrons, as well as the discussions of its formation mechanism and the catalytic role in activating the O-2 molecule. Secondly, aiming at shedding light on the doping effect on tuning the oxygen vacancy formation in ceria-based solid solutions, we summarize the recent theoretical results of Ce1-xZrxO2 solid solutions in terms of the effect of dopant concentrations and crystal phases. A general model on O vacancy formation is also discussed; it consists of electrostatic and structural relaxation terms, and the vital role of the later is emphasized. Particularly, we discuss the crucial role of the localized structural relaxation patterns in determining the superb oxygen storage capacity in kappa-phase Ce1-xZr1-xO2. Thirdly, we briefly discuss some interesting findings for the oxygen vacancy formation in pure ceria nanoparticles (NPs) uncovered by DFT calculations and compare those with the bulk or extended surfaces of ceria as well as different particle sizes, emphasizing the role of the electrostatic field in determining the O vacancy formation.

Ab initio diffusional potential energy surface for CO chemisorption on Pd{110} at high coverage:Coupled translation and rotation

The ground state potential energy surface for CO chemisorption across Pd{110} has been calculated using density functional theory with gradient corrections at monolayer coverage. The most stable site corresponds well with the experimental adsorption heat, and it is found that the strength of binding to sites is in the following order: pseudo-short-bridge>atop>long-bridge>hollow. Pathways and transition states for CO surface diffusion, involving a correlation between translation and orientation, are proposed and discussed. (C) 1997 American Institute of Physics.

Finite element modelling of composite structures under crushing load

This paper details the theory and implementation of a composite damage model, addressing damage within a ply (intralaminar) and delamination (interlaminar), for the simulation of crushing of laminated composite structures. It includes a more accurate determination of the characteristic length to achieve mesh objectivity in capturing intralaminar damage consisting of matrix cracking and fibre failure, a load-history dependent material response, an isotropic hardening nonlinear matrix response, as well as a more physically-based interactive matrix-dominated damage mechanism. The developed damage model requires a set of material parameters obtained from a combination of standard and non-standard material characterisation tests. The fidelity of the model mitigates the need to manipulate, or "calibrate", the input data to achieve good agreement with experimental results. The intralaminar damage model was implemented as a VUMAT subroutine, and used in conjunction with an existing interlaminar damage model, in Abaqus/Explicit. This approach was validated through the simulation of the crushing of a cross-ply composite tube with a tulip-shaped trigger, loaded in uniaxial compression. Despite the complexity of the chosen geometry, excellent correlation was achieved with experimental results.

Predicting the crushing behaviour of composite material using high-fidelity finite element modelling

The capability to numerically model the crushing behaviour of composite structures will enable the efficient design of structures with high specific energy absorption capacity. This is particularly relevant to the aerospace and automotive industries where cabin structures need to be shown to be crashworthy. In this paper, a three-dimensional damage model is presented, which accurately represents the behaviour of composite laminates under crush loading. Both intralaminar and interlaminar failure mechanisms are taken into account. The crush damage model was implemented in ABAQUS/Explicit as a VUMAT subroutine. Numerical predictions are shown to agree well with experimental results, accurately capturing the intralaminar and interlaminar damage for a range of stacking sequences, triggers and composite materials. The use of measured material parameters required by the numerical models, without the need to ‘calibrate’ this input data, demonstrates this computational tool's predictive capabilities

Faith-based Non-Governmental Organizations in the Public Square

This chapter has both a methodological and a substantive aim. First, I suggest, using the role and function of NGOs in religiously related legal disputes as a paradigm example, the distinction between institutional, doctrinal, and theoretical approaches to the study of the relationship between religion and law is sometimes unhelpful, creating a barrier preventing us from understanding the phenomenon that we are examining. Instead, I suggest, a more integrated understanding, drawing on each of these approaches and seeing how they relate to each other, may well be more illuminating. The second aim of this chapter is to suggest, in a preliminary way, that the phenomenon of faith-based organizations should be more integrated than in the past into doctrinal and theoretical debates in the area of law and religion, in particular the problem of how liberal society is to engage with organized religion where there is a fundamental dispute as to who represents that religion, or as to what the basic tenets of that religion are.

Potential of hydrogel-forming and dissolving microneedles for use in paediatric populations

Development of formulations and drug delivery strategies for paediatric use is challenging, partially due to the age ranges within this population, resulting in varying requirements to achieve optimised patient outcomes. Although the oral route of drug delivery remains the preferred option, there are problematic issues, such as difficulty swallowing and palatability of medicines specific to this population. The parenteral route is not well accepted by children due to needle-related fear and pain. Accordingly, a plethora of alternative routes of drug administration have been investigated. Microneedles (MN) breach the stratum corneum (SC), the outermost layer of skin, increasing the number of drug substances amenable to transdermal delivery. This strategy involves the use of micron-sized needles to painlessly, and without drawing blood, create transient aqueous conduits in the SC. In this study, polymeric dissolving MN and hydrogel-forming MN were fabricated incorporating two model drugs commonly used in paediatric patients (caffeine and lidocaine hydrochloride). The potential efficacy of these MN for paediatric dosing was investigated via in vitro and in vivo studies. Views pertaining to MN technology were sought amongst school children in Northern Ireland, members of the UK general public and UK-based paediatricians, to determine perceived benefits, acceptance, barriers and concerns for adoption of this technology. In this study, polymeric MN were shown to substantially enhance skin permeability of the model therapeutic molecules in vitro and in vivo. In particular, hydrogel-forming MN led to a 6.1-fold increase in caffeine delivery whilst lidocaine HCl delivery was increased by 3.3-fold using dissolving MN in vitro. Application of caffeine-loaded MN led to a caffeine plasma concentration of 23.87μg/mL in rats at 24h. This research also highlighted a strong consensus regarding MN technology amongst schoolchildren, paediatricians and the general public, regarding potential use of MN in the paediatric population. Overall, 93.6% of general public respondents and 85.9% of paediatricians regarded the use of MN as a positive approach.

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.

Finite Element Analysis of the Enhanced Strength of Laterally Restrained RC Slabs

This paper presents the numerical simulation of the ultimate behaviour of 85 one-way and two-way spanning laterally restrained concrete slabs of variable thickness, span, reinforcement ratio, strength and boundary conditions reported in literature by different authors. The developed numerical model was described and all the assumptions were illustrated. ABAQUS, a Finite Element Analysis suite of software, was employed. Non-linear implicit static general analysis method offered by ABAQUS was used. Other analysis methods were also discussed in general in terms of application such as Explicit Dynamic Analysis and Riks method. The aim is to demonstrate the ability and efficacy of FEA to simulate the ultimate load behaviour of slabs considering different material properties and boundary conditions. The authors intended to present a numerical model that provides consistent predictions of the ultimate behaviour of laterally restrained slabs that could be used as an alternative for expensive real life testing as well as for the design and assessment of new and existing structures respectively. The enhanced strength of laterally-restrained slabs compared with conventional design methods predictions is believed to be due to compressive membrane action (CMA). CMA is an inherent phenomenon of laterally restrained concrete beams/slabs. The numerical predictions obtained from the developed model were in good correlation with the experimental results and with those obtained from the CMA method developed at the Queen’s University Belfast, UK.

Clinical potential of gene-directed enzyme prodrug therapy to improve radiation therapy in prostate cancer patients

Despite the advances in prostate cancer diagnosis and treatment, current therapies are not curative in a significant proportion of patients. Gene-directed enzyme prodrug therapy (GDEPT), when combined with radiation therapy, could improve the outcome of treatment for prostate cancer, the second leading cause of cancer death in the western world. GDEPT involves the introduction of a therapeutic transgene, which can be targeted to the tumour cells. A prodrug is administered systemically and is converted to its toxic form only in those cells containing the transgene, resulting in cell kill. This review will discuss the clinical trials which have investigated the potential of GDEPT at various stages of prostate cancer progression. The advantages of using GDEPT in combination with radiotherapy will be examined, as well as some of the recent advances which enhance the potential utility of GDEPT.

Glacial cirques as palaeoenvironmental indicators: their potential and limitations

Glacial cirques are armchair-shaped erosional hollows, typified by steep headwalls and, often, overdeepened floors. They reflect former regions of glacier initiation, and their distribution is, therefore, linked to palaeoclimate. Because of this association, cirques can be analysed for the information they provide about past environments, an approach that has a strong heritage, and has seen resurgence over recent years. This paper provides a critical assessment of what cirques can tell us about past environments, and considers their reliability as palaeoenvironmental proxies. Specific focus is placed on information that can be obtained from consideration of cirque distribution, aspect, altitude, and morphometry. The paper highlights the fact that cirques potentially provide information about the style, duration and intensity of former glaciation, as well as information about past temperatures, precipitation gradients, cloud-cover and wind directions. In all, cirques are considered a valuable source of palaeoenvironmental information (if used judiciously), particularly as they are ubiquitous within formerly glaciated mountain ranges globally, thus making regional or even global scale studies possible. Furthermore, cirques often occupy remote and inaccessible regions where other palaeoenvironmental proxies may be limited or lacking.

Rethinking Prison Disciplinary Processes: A Potential Future for Restorative Justice

The movement for restorative justice (RJ) has struggled with marginalization on the soft end of the criminal justice system where the threat of net widening and iatrogenesis looms large. To realize the full potential of RJ as an alternative philosophy of justice, restorative practices need to expand beyond the world of adolescent and small-level offences into the deeper end of the justice system. Disciplinary hearings inside of adult prisons may be a strategic space to advance this expansion. This paper presents findings from a study of prison discipline in four UK prisons. The findings strongly suggest that in their current form, such disciplinary proceedings are viewed by prisoners as lacking in legitimacy. Although modelled after the adversarial system of the criminal court, the adjudications were instead universally derided as ‘kangaroo courts’, lacking in the basic elements of procedural justice. Based on these findings, we argue that restorative justice interventions may offer a viable redress to these problems of legitimacy which, if successful, would have ramifications that extend well beyond the prison walls.

Visual morbidity due to inaccurate spectacles among school children in rural China: the See Well to Learn Well Project, report 1.

PURPOSE: Inadequately corrected refractive error is the leading cause of visual disability among children in China; inaccurate spectacles are a potential cause. The prevalence and visual impact of spectacle inaccuracy were studied among rural, secondary-school children, to determine the optimal timing for updating of refraction. METHODS: A random sample of children from years 1 and 2 in all junior and senior high schools in Fuyang Township, Guangdong Province, underwent ocular examination. All children who reported wearing glasses received cycloplegic refraction, vision assessment, and measurement of current spectacles. RESULTS: Among 3226 examined children, 733 (22.7%) reported owning spectacles. Refractive error and spectacle power were assessed for 588 (80.2%) children. They had a mean age of 15.0 +/- 1.6 years; 70.2% were girls, 83.3% had more than -1.5 D of myopia, and 17.9% had presenting vision < or = 6/12 in the better eye. The glasses of 48.8% of children were inaccurate by > or = 1 D; inaccuracy was > or = 2 D in 17.7%. Children with inaccurate glasses (> or = 1 D) had presenting vision in the better eye significantly (P < 0.001) worse than that of children with accurate glasses, and 30.3% had presenting acuity < or = 6/12. In multivariate models, younger age (P = 0.004), more myopic refractive error (P < 0.001), and having glasses > or = 1 year old (P = 0.04) were associated with inaccurate spectacles. DISCUSSION: Inaccurate spectacles are common and are associated with significant visual impairment among children in rural China. Reducing outdated glasses could lessen the visual burden, although refractive services may have to be offered on an annual basis for optimal benefit.

Modelling of Evaporator in Waste Heat Recovery System using Finite Volume Method and Fuzzy Technique

The evaporator is an important component in the Organic Rankine Cycle (ORC)-based Waste Heat Recovery (WHR) system since the effective heat transfer of this device reflects on the efficiency of the system. When the WHR system operates under supercritical conditions, the heat transfer mechanism in the evaporator is unpredictable due to the change of thermo-physical properties of the fluid with temperature. Although the conventional finite volume model can successfully capture those changes in the evaporator of the WHR process, the computation time for this method is high. To reduce the computation time, this paper develops a new fuzzy based evaporator model and compares its performance with the finite volume method. The results show that the fuzzy technique can be applied to predict the output of the supercritical evaporator in the waste heat recovery system and can significantly reduce the required computation time. The proposed model, therefore, has the potential to be used in real time control applications.