The level of BMP4 signaling is critical for the regulation of distinct T-box gene expression domains and growth along the dorso-ventral axis of the optic cup

Background: Polarised gene expression is thought to lead to the graded distribution of signaling molecules providing a patterning mechanism across the embryonic eye. Bone morphogenetic protein 4 (Bmp4) is expressed in the dorsal optic vesicle as it transforms into the optic cup. Bmp4 deletions in human and mouse result in failure of eye development, but little attempt has been made to investigate mammalian targets of BMP4 signaling. In chick, retroviral gene overexpression studies indicate that Bmp4 activates the dorsally expressed Tbx5 gene, which represses ventrally expressed cVax. It is not known whether the Tbx5 related genes, Tbx2 and Tbx3, are BMP4 targets in the mammalian retina and whether BMP4 acts at a distance from its site of expression. Although it is established that Drosophila Dpp ( homologue of vertebrate Bmp4) acts as a morphogen, there is little evidence that BMP4 gradients are interpreted to create domains of BMP4 target gene expression in the mouse.Results: Our data show that the level of BMP4 signaling is critical for the regulation of distinct Tbx2, Tbx3, Tbx5 and Vax2 gene expression domains along the dorso-ventral axis of the mouse optic cup. BMP4 signaling gradients were manipulated in whole mouse embryo cultures during optic cup development, by implantation of beads soaked in BMP4, or the BMP antagonist Noggin, to provide a local signaling source. Tbx2, Tbx3 and Tbx5, showed a differential response to alterations in the level of BMP4 along the entire dorso-ventral axis of the optic cup, suggesting that BMP4 acts across a distance. Increased levels of BMP4 caused expansion of Tbx2 and Tbx3, but not Tbx5, into the ventral retina and repression of the ventral marker Vax2. Conversely, Noggin abolished Tbx5 expression but only shifted Tbx2 expression dorsally. Increased levels of BMP4 signaling caused decreased proliferation, reduced retinal volume and altered the shape of the optic cup.Conclusion: Our findings suggest the existence of a dorsal-high, ventral-low BMP4 signaling gradient across which distinct domains of Tbx2, Tbx3, Tbx5 and Vax2 transcription factor gene expression are set up. Furthermore we show that the correct level of BMP4 signaling is critical for normal growth of the mammalian embryonic eye

Computer program calculates the effective temperature for a crystalline solid /DETS/

Computer program computes and prints out both the Debye and resulting effective temperatures for each Debye model-dependent average energy per vibrational mode, Debye-Waller factor, and specific heat. The program calculates by the trapezodial rule and then Simpsons rule

Assessing reporting of narrative synthesis of quantitative data in public health systematic reviews

No abstract available

Life under siege: Nottingham during the English civil war (1642-46)

Nottingham was an important town during the British Civil Wars of the 1630s and 40s. Despite the King raising his standard in the town it rapidly became a stronghold for Parliament, and its residents became embroiled in one of the fiercest areas of fighting in the country. This research builds on and extends the 'county study' approach in novel ways; rather than focusing on political and military events it concentrates on the experiences of Nottingham's population and interprets the impact of the Civil Wars on everyday life. It attempts to reconstruct and understand the civilian experience of a garrison town during a period of often brutal civil war. Adopting innovative ways of reading the past, it incorporates soundscapes and 'history from below' in a way which shines a spotlight on the masses rather than the elite during Nottingham's difficult transformation from market and county town to fortified stronghold

Is access to and use of Exercise Referral Schemes equitable?

Exercise Referral Schemes (ERSs) are a widespread multi-agency intervention in which patients are referred to a programme of supervised sessions of subsidised exercise at a local leisure centre. National guidance states that schemes should employ strategies to engage people from disadvantaged groups. While people from such groups are known to attend primary care more frequently than those from more advantaged socioeconomic groups, research suggests that they are less likely to use preventive and specialist health services. This thesis aims to evaluate whether access to and use of ERSs is equitable through an examination of socioeconomic differences in referral, uptake and completion of the service. Firstly, the thesis presents a case study of key research, policy and practice events concerning the development of ERSs. Secondly, the thesis details findings of a scoping review undertaken across all ERSs in Greater London to identify schemes with suitable routine data collection to participate in the equity analysis. Thirdly, the thesis presents a cross-sectional analysis of 7985 patients referred by general practices to ERSs operating in six PCTs between April 2004 - March 2006. The main outcome measures were i) risk ratios for referral by general practice deprivation quintile ii) odds ratios for uptake of ERSs and iii) odds ratios for completion of ERSs by patient deprivation quintile. Fourthly, an exploration of the added value of using a geodemographic segmentation tool to enhance understanding of socioeconomic inequalities in service utilisation at small-area level is described. This research found that general practices within deprived areas were more likely to refer patients to ERSs than their counterparts in more advantaged areas. There was no evidence of an association between socioeconomic circumstance and likelihood of either taking up or completing the scheme. The implications of this research for policy, practice and future research are discussed

Determining ground-level composition and concentration of particulate matter across regional areas using the Himawari-8 satellite

Speciated ground-level aerosol concentrations are required to understand and mitigate health impacts from dust storms, wildfires and other aerosol emissions. Globally, surface monitoring is limited due to cost and infrastructure demands. While remote sensing can help estimate respirable (i.e. ground level) concentrations, current observations are restricted by inadequate spatiotemporal resolution, uncertainty in aerosol type, particle size, and vertical profile. One key issue with current remote sensing datasets is that they are derived from reflectances observed by polar orbiting imagers, which means that aerosol is only derived during the daytime, and only once or twice per day. Sub-hourly, infrared (IR), geostationary data, such as the ten-minute data from Himawari-8, are required to monitor these events to ensure that sporadic dust events can be continually observed and quantified. Newer quantification methods using geostationary data have focussed on detecting the presence, or absence, of a dust event. However, limited attention has been paid to the determination of composition, and particle size, using IR wavelengths exclusively. More appropriate IR methods are required to quantify and classify aerosol composition in order to improve the understanding of source impacts. The primary research objectives were investigated through a series of scientific papers centred on aspects deemed critical to successfully determining ground-level concentrations. A literature review of surface particulate monitoring of dust events using geostationary satellite remote sensing was undertaken to understand the theory and limitations in the current methodology. The review identified (amongst other findings) the reliance on visible wavelengths and the lack of temporal resolution in polar-orbiting satellite data. As a result of this, a duststorm was investigated to determine how rapidly the storm passed and what temporal data resolution is required to monitor these and other similar events. Various IR dust indices were investigated to determine which are optimum for determining spectral change. These indices were then used to qualify and quantitate dust events, and the methodology was validated against three severe air quality events of a dust storm; smoke from prescribed burns; and an ozone smog incident. The study identified that continuous geostationary temporal resolution is critical in the determination of concentration. The Himawari-8 spatial resolution of 2 km is slightly coarse and further spatial aggregation or cloud masking would be detrimental to determining concentrations. Five dual-band BTD combinations, using all IR wavelengths, maximises the identification of compositional differences, atmospheric stability, and cloud cover and this improves the estimated accuracy. Preliminary validation suggests that atmospheric stability, cloud height, relative humidity, PM2.5, PM10, NO, NO2, and O3 appear to produce plausible plumes but that aerosol speciation (soil, sea-spray, fires, vehicles, and secondary sulfates) and SO2 require further investigation. The research described in the thesis details the processes adopted for the development and implementation of an integrated approach to using geostationary remote sensing data to quantify population exposure (who), qualify the concentration and composition (what), assess the temporal (when) and spatial (where) concentration distributions, to determine the source (why) of aerosols contribution to resulting ground-level concentration

Click, swipe, download, share: Digital artists’ publishing

In this article, the British artist Tom Sowden looks at some of the ways in which other artists are publishing their books digitally. From hypertext works to ebooks to blogging; artists are beginning to utilize purely digital publishing tools as a method of producing artists’ books. Their reasons for doing so range from the ease of distribution to a larger audience, to creating a completely new reading experience, to making comments on the move from physical to digital, or at times in order to minimise production costs. Taking a small selection of works that heconsiders to be important in the lexicon of digital artists’ books, Sowden assesses how artists are using the technology available, what they are doing with it, andwhether he considers it successful. Not an exhaustive list, but some key works that are conceptually sound, while demonstrating the myriad ways in which digital technologiescan be utilised. By its very nature the digital world is continually adapting, changing and improving, so these worksare only a snapshot of what has happened in the recent past and what is happening now.Written from the viewpoint of a practising artist who makes books, the interest in how digital publications can influence artist’s book practice is approached from different angles. It is a keen observation of his peers’ production methods and how new technologies have developed their practice and its content. It is also a survey ofhow widely these publishing methods are being utilised and offered by artists. It is also Sowden watching how things develop and how new technologies could possibly influence his practice

Exploring appropriation as a creative practice

During the 1960s and 1970s, Ed Ruscha produced a series of 16 small, self-published books that became a catalyst for how artists could approach the book form. This reputation has grown through the subsequent decades, and his influence on book artists remains strong to this day to the extent that his books have been, and continue to be, appropriated across the world by successive generations of artists. Writing from a practitioner perspective, I will begin by looking at how Ruscha has become so influential to generations of book artists. I will look at what influenced him, and how he may possibly have appropriated the work of others. I will then focus in on the community of book artists who reference Ruscha’s books in their practice. The research of Ruscha’s books is embodied in each of these individual outcomes, but I will show that it is through the collective act and the bringing together of all of these books, through the community, that the work/s gain currency, strengthening both the Ruscha books and those that have come after