Representation and use of chemistry in the global electronic age.

We present an overview of the current state of public semantic chemistry and propose new approaches at a strategic and a detailed level. We show by example how a model for a Chemical Semantic Web can be constructed using machine-processed data and information from journal articles.This manuscript addresses questions of robotic access to data and its automatic re-use, including the role of Open Access archival of data. This is a pre-refereed preprint allowed by the publisher's (Royal Soc. Chemistry) Green policy. The author's preferred manuscript is an HTML hyperdocument with ca. 20 links to images, some of which are JPEgs and some of which are SVG (scalable vector graphics) including animations. There are also links to molecules in CML, for which the Jmol viewer is recommended. We susgeest that readers who wish to see the full glory of the manuscript, download the Zipped version and unpack on their machine. We also supply a PDF and DOC (Word) version which obviously cannot show the animations, but which may be the best palce to start, particularly for those more interested in the text

Regional Economic Implications of Water Allocation and Reliability

The understanding of how allocation decisions can maximise the economic returns to the community from water for irrigation has received little attention, but is a significant issue for regional councils, those interested in water allocation policy development, and for irrigated farmers. There is a tradeoff between the amount of irrigated area and the reliability with which it can be undertaken. Overseas studies have generated a curve with optimum levels of allocation which maximise the economic return to the community from the resource. The study on which this paper is based used a single case study to model the individual and regional economic outcomes for four scenarios of water allocation, using daily time step simulation models of the hydrological, irrigation, farm and financial systems over the 1973 – 2000 period. The results show that there is an increasing return to the region as the allocation from the resource increases, at the expense of lower returns to existing users.Irrigation, reliability, regional economic impacts, Agribusiness, Agricultural and Food Policy, Agricultural Finance, Community/Rural/Urban Development, Environmental Economics and Policy, Farm Management, Financial Economics, Institutional and Behavioral Economics, Land Economics/Use, Resource /Energy Economics and Policy,

Management of leiomyosarcomas of the spermatic cord: the role of reconstructive surgery

BACKGROUND: Leiomyosarcomas (LMS) of the spermatic cord are extremely rare. Radical inguinal orchiectomy and high ligation of the cord is the standard primary surgical procedure. The extent of surrounding soft tissue excision required and the precise role of adjuvant radiotherapy, however, remains unclear. In addition, recurrence is a commonly encountered problem which might necessitate further radical excision of adjacent soft tissues. METHODS: This article reviews the pathophysiology of spermatic cord leiomyosarcomas (LMS), and discusses the various reconstructive surgical options available to repair the inguinal region and the lower anterior abdominal wall after excision of the tumour and the adjacent soft tissues. RESULTS: There is paucity of literature on LMS of spermatic cord. The majority of paratesticular neoplasms are of mesenchymal origin and up to 30% of these are malignant. In adults, approximately 10% of spermatic cord sarcomas are LMS. Approximately 50% of these tumours recur loco-regionally following definitive surgery; however, the incidence decreases if resection is followed by adjuvant radiotherapy. CONCLUSION: It is therefore important to achieve negative histological margins during the primary surgical procedure, even if adjuvant radiotherapy is instituted. If extensive resection is required, either during the primary procedure or following recurrence, reconstructive surgery may become necessary. This article reviews the pathophysiology of spermatic cord LMS, the reasons for recurrence, and discusses the management options including the role of reconstructive surgery

Compartmentalized megakaryocyte death generates functional platelets committed to caspase-independent death

Caspase-directed apoptosis usually fragments cells, releasing nonfunctional, prothrombogenic, membrane-bound apoptotic bodies marked for rapid engulfment by macrophages. Blood platelets are functional anucleate cells generated by specialized fragmentation of their progenitors, megakaryocytes (MKs), but committed to a constitutive caspase-independent death. Constitutive formation of the proplatelet-bearing MK was recently reported to be caspase-dependent, apparently involving mitochondrial release of cytochrome c, a known pro-apoptogenic factor. We extend those studies and report that activation of caspases in MKs, either constitutively or after Fas ligation, yields platelets that are functionally responsive and evade immediate phagocytic clearance, and retain mitochondrial transmembrane potential until constitutive platelet death ensues. Furthermore, the exclusion from the platelet progeny of caspase-9 present in the progenitor accounts for failure of mitochondrial release of cytochrome c to activate caspase-3 during platelet death. Thus, progenitor cell death by apoptosis can result in birth of multiple functional anucleate daughter cells

Global magnetohydrodynamic simulation of the 15 March 2013 coronal mass ejection event-Interpretation of the 30-80 MeV proton flux

The coronal mass ejection (CME) event on 15 March 2013 is one of the few solar events in Cycle 24 that produced a large solar energetic particle (SEP) event and severe geomagnetic activity. Observations of SEP from the ACE spacecraft show a complex time-intensity SEP profile that is not easily understood with current empirical SEP models. In this study, we employ a global three-dimensional (3-D) magnetohydrodynamic (MHD) simulation to help interpret the observations. The simulation is based on the H3DMHD code and incorporates extrapolations of photospheric magnetic field as the inner boundary condition at a solar radial distance (r) of 2.5 solar radii. A Gaussian-shaped velocity pulse is imposed at the inner boundary as a proxy for the complex physical conditions that initiated the CME. It is found that the time-intensity profile of the high-energy (>10 MeV) SEPs can be explained by the evolution of the CME-driven shock and its interaction with the heliospheric current sheet and the nonuniform solar wind. We also demonstrate in more detail that the simulated fast-mode shock Mach number at the magnetically connected shock location is well correlated (r_(cc) ≥ 0.7) with the concurrent 30–80 MeV proton flux. A better correlation occurs when the 30–80 MeV proton flux is scaled by r^(−1.4)(r_(cc) = 0.87). When scaled by r^(−2.8), the correlation for 10–30 MeV proton flux improves significantly from r_(cc) = 0.12 to r_(cc) = 0.73, with 1 h delay. The present study suggests that (1) sector boundary can act as an obstacle to the propagation of SEPs; (2) the background solar wind is an important factor in the variation of IP shock strength and thus plays an important role in manipulation of SEP flux; (3) at least 50% of the variance in SEP flux can be explained by the fast-mode shock Mach number. This study demonstrates that global MHD simulation, despite the limitation implied by its physics-based ideal fluid continuum assumption, can be a viable tool for SEP data analysis

Gas6 Increases Myelination by Oligodendrocytes and Its Deficiency Delays Recovery following Cuprizone-Induced Demyelination

Multiple sclerosis (MS) is a complex demyelinating disease of the central nervous system. Current research has shown that at least in some cases, the primary insult in MS could be directed at the oligodendrocyte, and that the earliest immune responses are primarily via innate immune cells. We have identified a family of receptor protein tyrosine kinases, known as the TAM receptors (Tyro3, Axl and Mertk), as potentially important in regulating both the oligodendrocyte and immune responses. We have previously shown that Gas6, a ligand for the TAM receptors, can affect the severity of demyelination in mice, with a loss of signalling via Gas6 leading to decreased oligodendrocyte survival and increased microglial activation during cuprizone-induced demyelination. We hypothesised TAM receptor signalling would also influence the extent of recovery in mice following demyelination. A significant effect of the absence of Gas6 was detected upon remyelination, with a lower level of myelination after 4 weeks of recovery in comparison with wild-type mice. The delay in remyelination was accompanied by a reduction in oligodendrocyte numbers. To understand the molecular mechanisms that drive the observed effects, we also examined the effect of exogenous Gas6 in in vitro myelination assays. We found that Gas6 significantly increased myelination in a dose-dependent manner, suggesting that TAM receptor signalling could be directly involved in myelination by oligodendrocytes. The reduced rate of remyelination in the absence of Gas6 could thus result from a lack of Gas6 at a critical time during myelin production after injury. These findings establish Gas6 as an important regulator of both CNS demyelination and remyelination

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA

Hysteretic thermal spin-crossover in heteroleptic Fe(II) complexes using alkyl chain substituted 2,2’-dipyridylamine ligands

The alkyl chain carrying ligands N,N-di(pyridin-2-yl)butanamide (LC4) and N,N-di(pyridin-2-yl)decanamide (LC10) were combined with NCS− co-ligands to form the neutral heteroleptic Fe(II) complexes trans-[FeII(LC4)2(NCS)2] (1C4) and trans-[FeII(LC10)2(NCS)2] (1C10). Variable temperature crystallographic studies revealed that 1C4 is in the orthorhombic space group Pna21 between 85–200 K whereas 1C10 is in the monoclinic space group P21/c between 85–140 K. The average Fe–N bond lengths suggest that at 85 K 1C4 contains LS Fe(II) centres; however, the ca. 0.18 Å increase in the average Fe–N bond lengths between 85 and 120 K suggests a spin-transition to the HS state occurs within this temperature interval. 1C10 contains LS Fe(II) centres between 85 and 105 K. Upon warming from 105 to 140 K the average Fe–N bond lengths increase by ca. 0.19 Å, which suggests a spin-transition to the HS state. Solid-state magnetic susceptibility measurements showed that 1C4 undergoes semi-abrupt spin-crossover with T1/2 = 127.5 K and a thermal hysteresis of ca. 13 K whereas, 1C10 undergoes an abrupt spin-crossover with T1/2 = 119.0 K, and is also accompanied by thermal hysteresis of ca. 4 K. The crystallographic and magnetic data show that the length of the complex's alkyl chain substituents can have a large impact on the structure of the crystal lattice as well as a subtle effect on the T1/2 value for thermal spin-crossover