Four independent gene phylogenies confirm the ancient relationships of Madagascar endemic species in the Papilio demoleus group (Lepidoptera, Papilionidae).

Madagascar is home to numerous endemic species and lineages, but the processes that have contributed to its endangered diversity are still poorly understood. Evidence is accumulating to demonstrate the importance of Tertiary dispersal across varying distances of oceanic barriers, supplementing vicariance relationships dating back to the Cretaceous, but these hypotheses remain tentative in the absence of well-supported phylogenies. In the Papilio demoleus group of swallowtail butterflies, three of the five recognized species are restricted to Madagascar, whereas the remaining two species range across the Afrotropical zone and southern Asia plus Australia. We reconstructed phylogenetic relationships for all species in the P. demoleus group, as well as 11 outgroup Papilio species, using 60 morphological characters and about 4 kb of nucleotide sequences from two mitochondrial (cytochrome oxidase I and II) and two nuclear (wg and EF-1a) genes. Of the three endemic Malagasy species, the two that are formally listed as endangered or at risk represented the most basal divergences in the group, while the more common third endemic was clearly related to African P. demodocus. The fifth species, P. demoleus, showed little differentiation across southern Asia, but showed divergence from its subspecies sthenelus in Australia. Dispersal-vicariance analysis using cladograms derived from morphology and three independent genes indicated a Malagasy diversification of lime swallowtails in the middle Miocene. Thus, diversification processes on the island of Madagascar may have contributed to the origin of common butterflies that now occur throughout much of the Old World tropical and subtemperate regions. An alternative hypothesis, that Madagascar is a refuge for ancient lineages resulting from successive colonizations from Africa, is less parsimonious and does not explain the relatively low continental diversity of the group.

Wavelength Dependence of Raman Enhancement from Gold Nanorod Arrays: Quantitative Experiment and Modeling of a Hot Spot Dominated System

Surface-enhanced Raman scattering (SERS) spectra from molecules adsorbed on the surface of vertically aligned gold nanorod arrays exhibit a variation in enhancement factor (EF) as a function of excitation wavelength that displays little correlation with the elastic optical properties of the surface. The key to understanding this lack of correlation and to obtaining agreement between experimental and calculated EF spectra lies with consideration of randomly distributed, sub-10 nm gaps between nanorods forming the substrate. Intense fields in these enhancement “hot spots” make a dominant contribution to the Raman scattering and have a very different spectral profile to that of the elastic optical response. Detailed modeling of the electric field enhancement at both excitation and scattering wavelengths was used to quantitatively predict both the spectral profile and the magnitude of the observed EF.

High-Frequency Ultrasound Assessment of the Murine Heart From Embryo Through to Juvenile

Aim: The aim of this study is to assess the murine heart of normal embryos, neonates, and juveniles using high-frequency ultrasound. Methods: Diastolic function was measured with E/A ratio (E wave velocity/A wave velocity) and isovolumetric relaxation time (IRT), systolic function with isovolumetric contraction time (ICT), percentage fractional shortening (FS%), percentage ejection fraction (EF%). Global cardiac performance was quantified using myocardial performance index (MPI). Results: Isovolumetric relaxation time remained stable from E10.5 to 3 weeks. Systolic function (ICT) improved with gestation and remained stable from E18.5 onward. Myocardial performance index showed improvement in embryonic lift (0.82-0.63) and then stabilized from 1 to 3 week (0.60-0.58). Percentage ejection fraction remained high during gestation (77%-69%) and then decreased from the neonate to juvenile (68%-51%). Conclusion: The ultrasound biomicroscope allows for noninvasive in-depth assessment of cardiac function of embryos and pups. Detailed physiological and functional cardiac function readouts can be obtained, which is invaluable for comparison to mouse models of disease.

Association of LETM1 and MRPL36 Contributes to the Regulation of Mitochondrial ATP Production and Necrotic Cell Death

Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is a mitochondrial inner membrane protein that was first identified in Wolf-Hirschhorn syndrome, and was deleted in nearly all patients with the syndrome. LETM1 encodes for the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of unclear function. Here, we describe LETM1-mediated regulation of mitochondrial ATP production and biogenesis. We show that LETM1 overexpression can induce necrotic cell death in HeLa cells, in which LETM1 reduces mitochondria) biogenesis and ATP production. LETM1 acts as an anchor protein and associates with mitochondrial ribosome protein L36. Adenovirus-mediated overexpression of LETM1 reduced mitochondrial mass and expression of many mitochondrial proteins. LETM1-mediated inhibition of mitochondrial biogenesis enhanced glycolytic ATP supply and activated protein kinase B activity and cell survival signaling. The expression levels of LETM1 were significantly increased in multiple human cancer tissues compared with normals. These data suggest that LETM1 serves as an anchor protein for complex formation with the mitochondrial ribosome and regulates mitochondrial biogenesis. The increased expression of LETM1 in human cancer suggests that deregulation of LETM1 is a key feature of tumorigenesis. [Cancer Res 2009;69(8):3397-404]

Analysis and Design of Class-E3F and Transmission-Line Class-E3F2 Power Amplifiers

In this paper, analysis and synthesis approach for two new variants within the Class-EF power amplifier (PA) family is elaborated. These amplifiers are classified here as Class-E3 F2 and transmission-line (TL) Class-E3 F 2. The proposed circuits offer means to alleviate some of the major issues faced by existing topologies such as substantial power losses due to the parasitic resistance of the large inductor in the Class-EF load network and deviation from ideal Class-EF operation due to the effect of device output inductance at high frequencies. Both lumped-element and transmission-line load networks for the Class-E 3 F PA are described. The load networks of the Class-E3 F and TL Class-E 3 F2amplifier topologies developed in this paper simultaneously satisfy the Class-EF optimum impedance requirements at fundamental frequency, second, and third harmonics as well as simultaneously providing matching to the circuit optimum load resistance for any prescribed system load resistance. Optimum circuit component values are analytically derived and validated by harmonic balance simulations. Trade-offs between circuit figures of merit and component values with some practical limitations being considered are discussed. © 2010 IEEE.

UK charity accounting: an exercise in widening stakeholder engagement

Given the economic and social impact of the charity sector in the United Kingdom (UK), the importance of good governance has been recognised as a basis for underpinning effective and ef?cient performance, and for ensuring that charities meet the legitimate aspirations of key stakeholders. A major aspect of this is high-quality accounting and reporting. Over the past 25 years attempts have been made to improve this through the medium of successive, evolving versions of a Statement of Recommended Practice (SORP) for charities. As a foundation for the future review of the SORP (expected to be published in 2015), the SORP Committee undertook its largest ever consultation on an accounting pronouncement. This paper presents the ?ndings of that consultation and, analysing them using stakeholder theory, concludes that this ambitious exercise facilitated much wider stakeholder engagement than had been experienced before and has the potential to legitimise further the SORP.

Identification of an acetylation-dependant Ku70/FLIP complex that regulates FLIP expression and HDAC inhibitor-induced apoptosis

FLIP is a potential anti-cancer therapeutic target that inhibits apoptosis by blocking caspase 8 activation by death receptors. We report a novel interaction between FLIP and the DNA repair protein Ku70 that regulates FLIP protein stability by inhibiting its polyubiquitination. Furthermore, we found that the histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) enhances the acetylation of Ku70, thereby disrupting the FLIP/Ku70 complex and triggering FLIP polyubiquitination and degradation by the proteasome. Using in vitro and in vivo colorectal cancer models, we further demonstrated that SAHA-induced apoptosis is dependant on FLIP downregulation and caspase 8 activation. In addition, an HDAC6-speci?c inhibitor Tubacin recapitulated the effects of SAHA, suggesting that HDAC6 is a key regulator of Ku70 acetylation and FLIP protein stability. Thus, HDAC inhibitors with anti-HDAC6 activity act as ef?cient post-transcriptional suppressors of FLIP expression and may, therefore, effectively act as ‘FLIP inhibitors’ © 2012 Macmillan Publishers Limited.

The Paralax Infrastructure: Automatic Parallelization With a Helping Hand

Speeding up sequential programs on multicores is a challenging problem that is in urgent need of a solution. Automatic parallelization of irregular pointer-intensive codes, exempli?ed by the SPECint codes, is a very hard problem. This paper shows that, with a helping hand, such auto-parallelization is possible and fruitful. This paper makes the following contributions: (i) A compiler framework for extracting pipeline-like parallelism from outer program loops is presented. (ii) Using a light-weight programming model based on annotations, the programmer helps the compiler to ?nd thread-level parallelism. Each of the annotations speci?es only a small piece of semantic information that compiler analysis misses, e.g. stating that a variable is dead at a certain program point. The annotations are designed such that correctness is easily veri?ed. Furthermore, we present a tool for suggesting annotations to the programmer. (iii) The methodology is applied to autoparallelize several SPECint benchmarks. For the benchmark with most parallelism (hmmer), we obtain a scalable 7-fold speedup on an AMD quad-core dual processor. The annotations constitute a parallel programming model that relies extensively on a sequential program representation. Hereby, the complexity of debugging is not increased and it does not obscure the source code. These properties could prove valuable to increase the ef?ciency of parallel programming.

The use of material flow analysis and the ecological footprint in regional policy-making: application and insights from Northern Ireland.

This paper aims to contribute to the ongoing debate on the use of resource accounting tools in regional policy making. The Northern Limits project applied Material Flow Analysis and Ecological Footprinting to regional policy making in Northern Ireland over a number of years. The early phase of the research informed the regions first sustainable development strategy which was published in 2006 with key targets relating to the Ecological Footprint and improving the resource efficiency of the economy. Phase II identified the next steps required to address data availability and quality and the use of MFA and EF in providing a measurement and monitoring framework for the strategy and in the development of the strategy implementation plan. The use of MFA and Ecological Footprinting in sustainable regional policy making and the monitoring of its implementation is an ongoing process which has raised a number of research issues which can inform the ongoing application and development of these and other resource accounting tools to within Northern Ireland, provide insights for their use in other regions and help set out the priorities for research to support this important policy area.

Monoenergetic Ion Beam Generation by Driving Ion Solitary Waves with Circularly Polarized Laser Light

Experimental data from the Trident Laser facility is presented showing quasimonoenergetic carbon ions from nm-scaled foil targets with an energy spread of as low as 15% at 35 MeV. These results and high resolution kinetic simulations show laser acceleration of quasimonoenergetic ion beams by the generation of ion solitons with circularly polarized laser pulses (500 fs, ¼ 1054 nm). The conversion ef?ciency into monoenergetic ions is increased by an order of magnitude compared with previous experimental results, representing an important step towards applications such as ion fast ignition.

Surface-Enhanced Raman Scattering from Metallic Nanostructures: Bridging the Gap between the Near-Field and Far-Field Responses

We present here a detailed study of the complex relationship between the electromagnetic near-field and far-field responses of "real" nanostructured metallic surfaces. The near-field and far-field responses are specified in terms of (spectra of) the surface-enhanced Raman-scattering enhancement factor (SERS EF) and optical extinction, respectively. First, it is shown that gold nanorod- and nanotube-array substrates exhibit three distinct localized surface plasmon resonances (LSPRs): a longitudinal, a transverse, and a cavity mode. The cavity mode simultaneously has the largest impact on the near-field behavior (as observed through the SERS EF) and the weakest optical interaction: It has a "near-field-type" character. The transverse and longitudinal modes have a significant impact on the far-field behavior but very little impact on SERS: They have a "far-field-type" character. We confirm the presence of the cavity mode using a combination of SERS EF spectra, electron microscopy, and electromagnetic modeling and thus clearly illustrate and explain the (lack of) correlation between the SERS EF spectra and the optical response in terms of the contrasting character of the three LSPRs. In doing so, we experimentally demonstrate that, for a surface that supports multiple LSPRs, the near-field and far-field properties can in fact be tuned almost independently. It is further demonstrated that small changes in geometrical parameters that tune the spectral location of the LPSRs can also drastically influence the character of these modes, resulting in certain unusual behavior, such as the far-field resonance redshift as the near-field resonance blueshifts. DOI: 10.1103/PhysRevX.3.011001

Electrical estimulation of retinal pigment epithelial cells

We investigated and characterized the effect of externally applied electric fields (EF) on retinal pigment epithelial (RPE) cells by exposing primary cultures of human RPE cells (hRPE) and those from the ARPE19 immortalized cell line to various strengths of EF (EF-treated cells) or to no EF (control cells) under different conditions including presence or absence of serum and gelatin and following wounding. We evaluated changes in RPE cell behavior in response to EF by using a computer based image capture and analysis system (Metamorph). We found that RPE cells responded to externally applied EFs by preferential orientation perpendicular to the EF vector, directed migration towards the anode, and faster translocation rate than control, untreated cells. These responses were voltage-dependent. Responses were observed even at low voltages, of 50-300 mV. Furthermore, the migration of hRPE cell sheets generated by wounding of confluent monolayers of cells at early and late confluence could be manipulated by the application of EF, with directed migration towards the anode observed at both sides of the wounded hRPE. In conclusion, RPE cell behaviour can be controlled by an externally applied EF. The potential for externally applied EF to be used as a therapeutic strategy in the management of selected retinal diseases warrants further investigation. © 2010 Elsevier Ltd.

The spark of life:The role of electric fields in regulating cell behaviour using the eye as a model system

Endogenous electric fields (EF) have long been known to influence cell behaviour during development, neural cell tropism, wound healing and cell behaviour generally. The effect is based on short circuiting of electrical potential differences across cell and tissue boundaries generated by ionic segregation. Recent in vitro and in vivo studies have shown that EF regulate not only cell movement but orientation of cells during mitosis, an effect which may underlie shaping of tissues and organs. The molecular basis of this effect is founded on receptor-mediated cell signalling events and alterations in cytoskeletal function as revealed in studies of gene deficient cells. Remarkably, not all cells respond directionally to EF in the same way and this has consequences, for instance, for lens development and vascular remodelling. The physical basis of EF effect may be related to changes induced in 'bound water' at the cell surface, whose organisation in association with trans-membrane proteins (e.g. receptors) is disrupted when EF are generated. Copyright © 2007 S. Karger AG.

Haptoglobin Phenotype, Preeclampsia and Response to Supplementation with Vitamins C and E in Pregnant Women with Type 1 Diabetes.

Objective The phenotype of the antioxidant and pro-angiogenicprotein haptoglobin (Hp) predicts cardiovascular disease risk andtreatment response to antioxidant vitamins in individuals withdiabetes. Our objective was to determine whether Hp phenotypeinfluences pre-eclampsia risk, or the efficacy of vitamins C and Ein preventing pre-eclampsia, in women with type-1 diabetes.
Design This is a secondary analysis of a randomised controlledtrial in which women with diabetes received daily vitamins C andE, or placebo, from 8 to 22 weeks of gestation until delivery.
Setting Twenty-five antenatal metabolic clinics across the UK (innorth-west England, Scotland, and Northern Ireland).
Population Pregnant women with type-1 diabetes.
Methods Hp phenotype was determined in white women whocompleted the study and had plasma samples available (n = 685).
Main outcome measure Pre-eclampsia.
Results Compared with Hp 2-1, Hp 1-1 (OR 0.59, 95% CI 0.30–1.16) and Hp 2-2 (OR 0.93, 95% CI 0.60–1.45) were notassociated with significantly decreased pre-eclampsia risk afteradjusting for treatment group and HbA1c at randomisation. Ourstudy was not powered to detect an interaction between Hpphenotype and treatment response; however, our preliminaryanalysis sugge sts that vitamins C and E did not prevent pre-eclampsia in women of any Hp phenotype (Hp 1-1, OR 0.77, 95%CI 0.22–2.71; Hp 2-1, OR 0.81, 95% CI 0.46–1.43; Hp 2-2, 0.67,95% CI 0.34–1.33), after adjusting for HbA1c at randomisation.
Conclusions The Hp phenotype did not significantly affect pre-eclampsia risk in women with type-1 diabetes.

Calcium binding proteins in the liver fluke, Fasciola hepatica

The common liver fluke, Fasciola hepatica, is a parasite of mammals. In the western world its effects are largely felt on agriculture where infection of cows, sheep and other farm animals is estimated to cause millions of dollars ofif financial losses. In the developing world, the problem is even more serious with an estimated 7 million infected people and many millions more at risk of infection. Calcium signalling is of key importance in all eukaryotic species and recent discoveries of novel types of calcium binding proteins in liver flukes (and related trematodes) suggest that there may be calcium signalling processes which are unique to this group of organisms. If so, these pathways may provide potential targets for the design of novel anthelmintic drugs. Here, we review three main groups of F. hepatica calcium binding proteins: the FH8 family, the calmodulin family (FhCaM1, FhCaM2 and FhCaM3) and the EF-hand/dynein light chain family (FH22, FhCaBP3, FhCaBP4). Considerable information has been gathered on the sequences, predicted structures and biochemical properties of these molecules. The challenge now is to understand their functions in the organism.