Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice

Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1 transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells (TCRβ+ CD4– CD8– B220+ ) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other haemopoietic cell types

Theory and design of Inx_{x}Ga1−x_{1-x}As1−y_{1-y}Biy_{y} mid-infrared semiconductor lasers: type-I quantum wells for emission beyond 3 μ\mum on InP substrates

We present a theoretical analysis and optimisation of the properties and performance of mid-infrared semiconductor lasers based on the dilute bismide alloy In$_{x}$Ga$_{1-x}$As$_{1-y}$Bi$_{y}$, grown on conventional (001) InP substrates. The ability to independently vary the epitaxial strain and emission wavelength in this quaternary alloy provides significant scope for band structure engineering. Our calculations demonstrate that structures based on compressively strained In$_{x}$Ga$_{1-x}$As$_{1-y}$Bi$_{y}$ quantum wells (QWs) can readily achieve emission wavelengths in the 3 -- 5 $\mu$m range, and that these QWs have large type-I band offsets. As such, these structures have the potential to overcome a number of limitations commonly associated with this application-rich but technologically challenging wavelength range. By considering structures having (i) fixed QW thickness and variable strain, and (ii) fixed strain and variable QW thickness, we quantify key trends in the properties and performance as functions of the alloy composition, structural properties, and emission wavelength, and on this basis identify routes towards the realisation of optimised devices for practical applications. Our analysis suggests that simple laser structures -- incorporating In$_{x}$Ga$_{1-x}$As$_{1-y}$Bi$_{y}$ QWs and unstrained ternary In$_{0.53}$Ga$_{0.47}$As barriers -- which are compatible with established epitaxial growth, provide a route to realising InP-based mid-infrared diode lasers.Comment: Submitted versio

How parents build a case for Autism Spectrum Disorder during initial assessments: “We’re fighting a losing battle”

Integral to the diagnosis of autism spectrum disorder (ASD) is the initial assessment through which the existence of a ‘problem’ is first ascertained. Despite this, there remains limited research on this early part of the diagnostic pathway. In this paper, we utilised conversation analysis to examine relevant issues in relation to the practitioner-family interactions that take place within this initial assessment context. Our findings illustrated that parents typically first raised the possibility of the presence of an ASD diagnosis through ‘building a case’, which professionals were then able to ratify or negate. Further, we found that the assessments unfolded sequentially and clinical decisions were typically reached through a distinctive pattern of interaction. These findings have important implications for clinical practice, including for the study of ASD assessments and diagnosis

Coordination Implications of Software Coupling in Open Source Projects

The effect of software coupling on the quality of software has been studied quite widely since the seminal paper on software modularity by Parnas [1]. However, the effect of the increase in software coupling on the coordination of the developers has not been researched as much. In commercial software development environments there normally are coordination mechanisms in place to manage the coordination requirements due to software dependencies. But, in the case of Open Source software such coordination mechanisms are harder to implement, as the developers tend to rely solely on electronic means of communication. Hence, an understanding of the changing coordination requirements is essential to the management of an Open Source project. In this paper we study the effect of changes in software coupling on the coordination requirements in a case study of a popular Open Source project called JBoss

Auger Recombination in Semiconductor Quantum Wells

The principal mechanisms of Auger recombination of nonequilibrium carriers in semiconductor heterostructures with quantum wells are investigated. It is shown for the first time that there exist three fundamentally different Auger recombination mechanisms of (i) thresholdless, (ii) quasi-threshold, and (iii) threshold types. The rate of the thresholdless Auger process depends on temperature only slightly. The rate of the quasi-threshold Auger process depends on temperature exponentially. However, its threshold energy essentially varies with quantum well width and is close to zero for narrow quantum wells. It is shown that the thresholdless and the quasi-threshold Auger processes dominate in narrow quantum wells, while the threshold and the quasi-threshold processes prevail in wide quantum wells. The limiting case of a three-dimensional (3D)Auger process is reached for infinitely wide quantum wells. The critical quantum well width is found at which the quasi-threshold and threshold Auger processes merge into a single 3D Auger process. Also studied is phonon-assisted Auger recombination in quantum wells. It is shown that for narrow quantum wells the act of phonon emission becomes resonant, which in turn increases substantially the coefficient of phonon-assisted Auger recombination. Conditions are found under which the direct Auger process dominates over the phonon-assisted Auger recombination at various temperatures and quantum well widths.Comment: 38 pages, 7 figure

Concerns of Ageing and Interest in Assistive Technologies – Convenience Sampling of Attendees at an Aged Care Technology Exhibition in China

Part 7: e-Health, the New Frontier of Service Science InnovationInternational audienceAs in many countries, ageing and aged care in China is an important issue. There is a need for more research on the potential for technology to assist older people and their families, particularly given the disappointing levels of adoption in developed countries. Accordingly this paper aims to gain insight into the perceptions of older people and stakeholders in relation to issues of ageing and their interest in adoption of technology. Using convenience sampling, the authors surveyed 277 participants to understand peoples concerns concerning ageing and use of technologies. Results from this study provide a basis for discussion with stakeholders, particularly concerning ageing in China

Charge and Orbital Ordering in Pr_{0.5} Ca_{0.5} MnO_3 Studied by ^{17}O NMR

The charge and orbital ordering in Pr_{0.5} Ca_{0.5} MnO_3 is studied for the first time by ^{17}O NMR. This local probe is sensitive to spin, charge and orbital correlations. Two transitions exist in this system: the charge and orbital ordering at T_{CO} = 225 K and the antiferromagnetic (AF) transition at T_N = 170 K. Both are clearly seen in the NMR spectra measured in a magnetic field of 7T. Above T_{CO} there exists only one NMR line with a large isotropic shift, whose temperature dependence is in accordance with the presence of ferromagnetic (FM) correlations. This line splits into two parts below T_{CO}, which are attributed to different types of oxygen in the charge/orbital ordered state. The interplay of FM and AF spin correlations of Mn ions in the charge ordered state of Pr_{0.5} Ca_{0.5} MnO_3 is considered in terms of the hole hopping motion that is slowed down with decreasing temperature. The developing fine structure of the spectra evidences, that there still exist charge-disordered regions at T_{CO} > T > T_N and that the static (t > 10^{-6}s) orbital order is established only on approaching T_N. The CE-type magnetic correlations develop gradually below T_{CO}, so that at first the AF correlations between checkerboard ab-layers appear, and only at lower temperature - CE correlations within the ab-planes

Acute phase proteins, interleukin 6, and heat shock protein 70 in broiler chickens administered with corticosterone

An experiment was conducted to determine the effect of corticosterone (CORT) administration on serum ovotransferrin (OVT), α1-acid glycoprotein (AGP), ceruloplasmin (CPN), and IL-6 concentrations, and brain heat shock protein (HSP) 70 expression in broiler chickens. From 14 to 20 d of age, equal numbers of birds were subjected to either (i) daily intramuscular injection with CORT in ethanol:saline (1:1, vol/vol) at 6 mg/kg of BW, or (ii) daily intramuscular injection with 0.5 mL ethanol:saline (1:1, vol/vol; control). Blood samples were collected before CORT treatment (14 d old), 3 and 7 d after CORT injections, and 4 d after cessation of CORT administration for determination of serum levels of CORT, OVT, AGP, CPN, and IL-6. Brain samples (whole cerebrum) were collected to measure HSP 70 density. Although CORT administration significantly increased feed intake, weight gain was significantly depressed. Administration of CORT also increased CORT, OVT, CPN, AGP, IL-6, and HSP 70 expression. Four days following cessation of CORT administration, OVT declined to the basal level but not CPN and AGP. In conclusion, an elevation in CORT can induce an acute-phase response and HSP 70 expression. Thus, APP and HSP 70 may be of value as indicators of stress in poultry