329 research outputs found
Heterozygous deletion of both sclerostin (Sost) and connexin43 (Gja1) genes in mice is not sufficient to impair cortical bone modeling
Connexin43 (Cx43) is the main gap junction protein expressed in bone forming cells, where it modulates peak bone mass acquisition and cortical modeling. Genetic ablation of the Cx43 gene (Gja1) results in cortical expansion with accentuated periosteal bone formation associated with decreased expression of the Wnt inhibitor sclerostin. To determine whether sclerostin (Sost) down-regulation might contribute to periosteal expansion in Gja1 deficient bones, we took a gene interaction approach and crossed mice harboring germline null alleles for Gja1 or Sost to generate single Gja1+/-and Sost+/-and double Gja1+/-;Sost+/-heterozygous mice. In vivo μCT analysis of cortical bone at age 1 and 3 months confirmed increased thickness in Sost-/-mice, but revealed no cortical abnormalities in single Gja1+/-or Sost+/-mice. Double heterozygous Gja1+/-Sost+/-also showed no differences in mineral density, cortical thickness, width or geometry relative to wild type control mice. Likewise, 3-point bending measurement of bone strength revealed no significant differences between double Gja1+/-;Sost+/-or single heterozygous and wild type mice. Although these data do not exclude a contribution of reduced sclerostin in the cortical expansion seen in Gja1 deficient bones, they are not consistent with a strong genetic interaction between Sost and Gja1 dictating cortical modeling
Recommended from our members
The siting of UK Nuclear Power Installations
choosing a suitable site for a nuclear installation requires the consideration and balancin9 of several factors which are sometimes in tension with one another. One particularly interesting tension is a human and demographic one. On the one hand it is beneficial to place nuclear stations close to centres of population, to reduce transmission losses and other costs (including to the local environment) of transporting electricity over large distances from generator to consumer. On the other it is advantageous to place nuclear stations some distance away from such population centres in order to minimise the potential human consequences of a major release of radioactive materials in the (extremely unlikely) event of a major nuclear accident, not only in terms of direct exposure but also concerning the management of emergency planning, notably evacuation. This paper considers the emergence of policies aimed at managing this tension in the UK. In the first phase of nuclear development (roughly speaking 1945 to 1965) there was a highly cautious attitude, with installations being placed in remote rural locations with verylow population density. The second phase (1965 to 1985) saw a more relaxed approach allowin9 Advanced Gas-Cooled Reactor construction closer to population centres (in 'semi-urban' locations, notably at Hartlepool and Heysham). In the third phase (1985 to 2005) there was very little new nuclear development, Sizewell B (the first and so far only pressurised water power reactor in the UK) being co-located with an early Magnox station on the rural Suffolk coast. However, there was considerable effort expended on trying to find a site for disposal of radioactive wastes. Renewed interest in nuclear new build grew from 2005 onwards and led to a number of sites being identified for new reactors before 2025; all having previously hosted nuclear stations and including the semi-urban locations of the 1960s and 1970s. Finally, some speculative comments are made as to what a 'fifth phase' starting in 2025 might look like
Compensating for severe nuclear accidents: An expert elucidation
We present the results of a structured discussion held in London in July 2014 involving a panel of experts drawn from three communities: specialists on aspects of risk and insurance; lawyers concerned with issues of nuclear law; and safety and environmental regulators. The discussions were held on the basis of participant anonymity. The process emphasised three considerations: conceptions of loss arising from a severe nuclear accident; the specifics of the Fukushima-Daiichi accident and what it means for policy and strategy going forward; and the future of liability regimes. We observe some stoicism from those closest to implementation of policies and procedures associated with nuclear risks, but a lower level of certainty and confidence among those concerned with nuclear energy regulation
The Order and Forme for Church Government by Bishops and the Clergie of This Kingdome. Voted in the House of Commons on Friday. Iuly 16. 1641. Whereunto Is Added Mr. Grimstons and Mr. Seldens Arguments Concerning Episcopacie
https://openworks.wooster.edu/notestein/1024/thumbnail.jp
Considerations in relation to off-site emergency procedures and response for nuclear accidents
The operation of nuclear facilities has, fortunately, not led to many accidents with off-site consequences. However, it is well-recognised that should a large release of radioactivity occur, the effects in the surrounding area and population will be significant. These effects can be mitigated by developing emergency preparedness and response plans prior to the operation of the nuclear facility that can be exercised regularly and implemented if an accident occurs. This review paper details the various stages of a nuclear accident and the corresponding aspects of an emergency preparedness plan that are relevant to these stages, both from a UK and international perspective. The paper also details how certain aspects of emergency preparedness have been affected by the accident at Fukushima Dai-ichi and as a point of comparison how emergency management plans were implemented following the accidents at Three Mile Island 2 and Chernobyl. In addition, the UK’s economic costing model for nuclear accidents COCO-2, and the UK’s Level-3 Probabilistic Safety Assessment code “PACE” are introduced. Finally, the factors that affect the economic impact of a nuclear accident, especially from a UK standpoint, are described
Predicting the cost of the consequences of a large nuclear accident in the UK
Nuclear accidents have the potential to lead to significant off-site effects that require actions to minimise the radiological impacts on people. Such countermeasures may include sheltering, evacuation, restrictions on the sale of locally-grown food, and long-term relocation of the population amongst others. Countries with nuclear facilities draw up emergency preparedness plans, and put in place such provisions as distributing instructions and iodine prophylaxis to the local population. Their plans are applied in simulated exercises on a regular basis. The costs associated with emergency preparedness and the safety provisions to reduce the likelihood of an accident, and/or mitigate the consequences, are justified on the basis of the health risks and accident costs averted. There is, of course, only limited actual experience to indicate the likely costs so that much of the costing of accidents is based on calculations. This paper reviews the methodologies used, in particular the approach that has been developed in the UK, to appraise the costs of a hypothetical nuclear accident.
Results of analysing a hypothetical nuclear accident at a fictitious reactor site within the United Kingdom are discussed in relation to the accidents at Three Mile Island 2, Chernobyl and Fukushima Dai-ichi
Marketing Renewable Energy in the United Kingdom
This chapter focuses on the renewable energy market in the UK. First we discuss the impact of privatization, then show what preconditions might be important. The main conclusion drawn from the analysis is that in the UK, as well as in other countries, new policy frameworks need to guide the transition from an energy system designed to achieve short-term efficiencies through market operation to a long-term approach that would embrace new uncertainties. Both market interests and environmental protection need to be secured in order to guarantee the levels of investment needed in the UK’s renewable energy market
Type XII collagen regulates osteoblast polarity and communication during bone formation
Type XII collagen–null mice have fragile bones with disorganized collagen fiber arrangement, decreased bone matrix formation, and delayed osteoblast differentiation
Biomechanics of the ankle
This paper provides an introduction to the biomechanics of the ankle, introducing the bony anatomy involved in motion of the foot and ankle. The complexity of the ankle anatomy has a significant influence on the biomechanical performance of the joint, and this paper discusses the motions of the ankle joint complex, and the joint at which it is proposed they occur. It provides insight into the ligaments that are critical to the stability and function of the ankle joint. It describes the movements involved in a normal gait cycle, and also highlights how these may change as a result of surgical intervention such as total joint replacement or fusion
Constitutively Activated NLRP3 Inflammasome Causes Inflammation and Abnormal Skeletal Development in Mice
The NLRP3 inflammasome complex is responsible for maturation of the pro-inflammatory cytokine, IL-1β. Mutations in NLRP3 are responsible for the cryopyrinopathies, a spectrum of conditions including neonatal-onset multisystem inflammatory disease (NOMID). While excessive production of IL-1β and systemic inflammation are common to all cryopyrinopathy disorders, skeletal abnormalities, prominently in the knees, and low bone mass are unique features of patients with NOMID. To gain insights into the mechanisms underlying skeletal abnormalities in NOMID, we generated knock-in mice globally expressing the D301N NLRP3 mutation (ortholog of D303N in human NLRP3). NOMID mice exhibit neutrophilia in blood and many tissues, including knee joints, and high levels of serum inflammatory mediators. They also exhibit growth retardation and severe postnatal osteopenia stemming at least in part from abnormally accelerated bone resorption, attended by increased osteoclastogenesis. Histologic analysis of knee joints revealed abnormal growth plates, with loss of chondrocytes and growth arrest in the central region of the epiphyses. Most strikingly, a tissue “spike" was observed in the mid-region of the growth plate in the long bones of all NOMID mice that may be the precursor to more severe deformations analogous to those observed in NOMID patients. These findings provide direct evidence linking a NOMID-associated NLRP3-activating mutation to abnormalities of postnatal skeletal growth and bone remodeling
- …