Herschel observations of NGC 7027

We present our analysis of the spectra of NGC 7027 taken with the PACS and SPIRE instruments of the Herschel satellite

Performance-based building and innovation: Balancing client and industry needs

One reason for the interest in performance-based building is that it is commonly advocated as a powerful way of enhancing innovation performance by articulating building performance outcomes, and by offering relevant procurement actors the discretion to innovate to meet these performance requirements more effectively and/or efficiently. The paper argues that the current approach to performance-based building assumes that relevant actors have the capacity, ability and motivation to innovate from a business perspective. It is proposed that the prevailing conceptualization of PBB is too restrictive and should be broadened explicitly to accommodate the required business logic that must be in place before actors will innovate. The relevant performance-based building and innovation literature is synthesized to support the assertion. The paper concludes with an innovation-focused definition of performance-based building

Specific orofacial problems experienced by musicians

Background: Patients who play musical instruments (especially wind and stringed instruments) and vocalists are prone to particular types of orofacial problems. Some problems are caused by playing and some are the result of dental treatment. This paper proposes to give an insight into these problems and practical guidance to general practice dentists. Method: Information in this paper is gathered from studies published in dental, music and occupational health journals, and from discussions with career musicians and music teachers. Results: Orthodontic problems, soft tissue trauma, focal dystonia, denture retention, herpes labialis, dry mouth and temporomandibular joint (TMJ) disorders were identified as orofacial problems of career musicians. Options available for prevention and palliative treatment as well as instrument selection are suggested to overcome these problems. Conclusions: Career musicians express reluctance to attend dentists who are not sensitive to their specific needs. General practitioner dentists who understand how the instruments impact on the orofacial structures and are aware of potential problems faced by musicians are able to offer preventive advice and supportive treatment to these patients, especially those in the early stages of their career

Defective platelet function in Niemann-Pick disease type C1

Niemann-Pick disease type C (NPC) is a neurodegenerative lysosomal storage disorder caused by mutations in either NPC1 (95% of cases) or NPC2. Reduced late endosome/lysosome calcium (Ca2+) levels and the accumulation of unesterified cholesterol and sphingolipids within the late endocytic system characterize this disease. We previously reported impaired lysosome-related organelle (LRO) function in Npc1−/− Natural Killer cells; however, the potential contribution of impaired acid compartment Ca2+ flux and LRO function in other cell types has not been determined. Here, we investigated LRO function in NPC1 disease platelets. We found elevated numbers of circulating platelets, impaired platelet aggregation and prolonged bleeding times in a murine model of NPC1 disease. Electron microscopy revealed abnormal ultrastructure in murine platelets, consistent with that seen in a U18666A (pharmacological inhibitor of NPC1) treated megakaryocyte cell line (MEG-01) exhibiting lipid storage and acidic compartment Ca2+ flux defects. Furthermore, platelets from NPC1 patients across different ages were found to cluster at the lower end of the normal range when platelet numbers were measured and had platelet volumes that were clustered at the top of the normal range. Taken together, these findings highlight the role of acid compartment Ca2+ flux in the function of platelet LROs

What Difference Does Quantity Make? On the Epistemology of Big Data Biology

publication-status: Acceptedtypes: ArticleIs Big Data science a whole new way of doing research? And what difference does data quantity make to knowledge production strategies and their outputs? I argue that the novelty of Big Data science does not lie in the sheer quantity of data involved, but rather in (1) the prominence and status acquired by data as commodity and recognised output, both within and outside of the scientific community and (2) the methods, infrastructures, technologies, skills and knowledge developed to handle data. These developments generate the impression that data-intensive research is a new mode of doing science, with its own epistemology and norms. To assess this claim, one needs to consider the ways in which data are actually disseminated and used to generate knowledge. Accordingly, this article reviews the development of sophisticated ways to disseminate, integrate and re-use data acquired on model organisms over the last three decades of work in experimental biology. I focus on online databases as prominent infrastructures set up to organise and interpret such data and examine the wealth and diversity of expertise, resources and conceptual scaffolding that such databases draw upon. This illuminates some of the conditions under which Big Data needs to be curated to support processes of discovery across biological subfields, which in turn highlights the difficulties caused by the lack of adequate curation for the vast majority of data in the life sciences. In closing, I reflect on the difference that data quantity is making to contemporary biology, the methodological and epistemic challenges of identifying and analysing data given these developments, and the opportunities and worries associated with Big Data discourse and methods.Economic and Social Research CouncilES/F028180/1Leverhulme TrustRPG-2013-153European Union’s Seventh Framework Programme (FP7/2007-2013ERC grant agreement number 335925

Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P<0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P<0.01) and thymidine kinase activity (P<0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P<0.05) in the rats treated with cyclosporine as compared to the vehicle. These results show that cyclosporine treatment causes an increase in the hepatic content of estrogen receptor activity that is associated with an enhanced potential for a regenerative response. These effects of cyclosporine treatment on the sex hormone receptor levels in liver may explain the mechanisms responsible for some of the untoward effects of treatment with this agent. © 1990 Plenum Publishing Corporation

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Effect of tamoxifen on hepatic regeneration in male rats

A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.1 mg/rat/day or 1.0 mg/rat/day) or vehicle for three days prior to and after partial hepatectomy, and the anatomic and biochemical process of hepatic regeneration was assessed. Tamoxifen administration caused a dose-dependent decrease in the hepatic cytosolic estrogen receptor activity and, conversely, a dose-dependent increase in cytosolic androgen receptor activity. Despite these changes in baseline hepatic sex steroid receptor status, all receptor activities were comparable between the three groups within 24 hr of partial hepatectomy. Moreover, no differences in any of the the parameters assessing hepatic regeneration following partial hepatectomy were evident: liver-body ratio, ornithine decarboxylase activity, and thymidine kinase activity. This lack of effect of tamoxifen treatment on hepatic regeneration suggests either that estrogens do not play a role in the modulation of liver growth after partial hepatectomy or that, once initiated, the regenerative process per se determines a series of events that regulate hepatocellular sex hormone receptor status independent of extrahepatic stimuli. © 1989 Plenum Publishing Corporation

Sociodemographic and geographic characteristics associated with patient visits to osteopathic physicians for primary care

<p>Abstract</p> <p>Background</p> <p>Health care reform promises to dramatically increase the number of Americans covered by health insurance. Osteopathic physicians (DOs) are recognized for primary care, including a "hands-on" style with an emphasis on patient-centered care. Thus, DOs may be well positioned to deliver primary care in this emerging health care environment.</p> <p>Methods</p> <p>We used data from the National Ambulatory Medical Care Survey (2002-2006) to study sociodemographic and geographic characteristics associated with patient visits to DOs for primary care. Descriptive analyses were initially performed to derive national population estimates (NPEs) for overall patient visits, primary care patient visits, and patient visits according to specialty status. Osteopathic and allopathic physician (MD) patient visits were compared using cross-tabulations and multiple logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) for DO patient visits. The latter analyses were also conducted separately for each geographic characteristic to assess the potential for effect modification based on these factors.</p> <p>Results</p> <p>Overall, 134,369 ambulatory medical care visits were surveyed, representing 4.6 billion (NPE) ± 220 million (SE) patient visits when patient visit weights were applied. Osteopathic physicians provided 336 million ± 30 million (7%) of these patient visits. Osteopathic physicians provided 217 million ± 21 million (10%) patient visits for primary care services; including 180 million ± 17 million (12%) primary care visits for adults (21 years of age or older) and 37 million ± 5 million (5%) primary care visits for minors. Osteopathic physicians were more likely than MDs to provide primary care visits in family and general medicine (OR, 6.03; 95% CI, 4.67-7.78), but were less likely to provide visits in internal medicine (OR, 0.37; 95% CI, 0.24-0.58) or pediatrics (OR, 0.21; 95% CI, 0.11-0.40). Overall, patients in the pediatric and geriatric ages, Blacks, Hispanics, and persons in the South and West were less likely to utilize DOs, although there was some evidence of effect modification according to United States Census region.</p> <p>Conclusions</p> <p>Health care reform provides unprecedented opportunities for DOs to reach historically underserved populations and to overcome the "pediatric primary-care paradox."</p