bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled fracture of Cu/ultralow-k interconnects
Authors: Li Han , Kobrinsky Mauro J. , Shariq Ahmed , Richards John , Liu Jimmy , Kuhn Markus
Published: December 2013

Mechanical failures of on-chip interconnects in the forms of delamination and cracking are among the most critical challenges for integrating ultralow-dielectric-constant (ultralow-“k”) materials in advanced integrated circuits. Designing a mechanically robust interconnect stack against fabrication and packaging stresses requires quantitative characterization of the fracture properties of the integrated structure and its component materials. In this Letter, we demonstrate a simple method to control crack propagation in Cu/ultralow-k interconnect and thereby extract the fracture properties of the metal vias and interlayer dielectrics from integrated structures. Important implications of the method are discussed for interconnect technology development and for fundamental study of fracture behaviors of materials having nano-scale structures.
Explanation of red spectral shifts at CdTe grain boundaries
Authors: Moseley J. , Al-Jassim M. M. , Moutinho H. R. , Guthrey H. L. , Metzger W. K. , Ahrenkiel R. K.
Published: December 2013

We use cathodoluminescence spectrum imaging to investigate the nanoscale properties of CdTe thin-films for solar cells deposited by close-spaced sublimation. Luminescence emission is detected (bands) at ∼1.32 eV and ∼1.50 eV, which are consistent with Z- and Y-bands. For the grains in the as-deposited films, there is a significant redshift in the transition energies near the grain boundaries. The high grain boundary recombination velocity and the donor-acceptor pair (DAP) mechanism of the Z-band transition account for the contrast between grain boundaries and the grain interior. By applying DAP theory, we estimate the concentration of the shallow donor species participating in the Z-band transition to be ∼1017 cm−3.
Giant pyroelectric coefficient determined from the frequency dependence of the pyroelectric signal generated by epitaxial Pb(Zr0.2Ti0.8)O3 layers grown on single crystal SrTiO3 substrates
Authors: Botea M. , Iuga A. , Pintilie L.
Published: December 2013

Epitaxial Pb(Zr0.2Ti0.8)O3 layers of good structural quality were grown on single crystal SrTiO3 substrates. The pyroelectric coefficient was estimated from the signal generated by the ferroelectric film working as a pyroelectric detector in the voltage mode, without pre-poling procedure. The obtained value is as high as 1.9 × 10−3 C/m2 K. The large value is attributed to the presence of 90° ferroelectric domains and to the compressive misfit strain, leading to an enhanced ferroelectric polarization.
Large magneto-chemical-elastic coupling in highly magnetostrictive Fe-Ga alloys
Authors: Narsu B. , Wang Gui-Sheng , Johansson B. , Vitos L.
Published: December 2013

The strong softening of the tetragonal shear elastic constant (C′) is the main reason for the second magnetostriction peak observed in Fe100–xGax alloys. Here, we study the coupling between chemical order and magnetism with the aim to understand the origin of the elastic softening. We demonstrate that C′ strongly depends on the degree of order of Ga atoms in α-Fe. The B2 type ordering proves to have an important role on the elastic softening for x<19%, whereas the extreme shear lattice softening and the anomalous temperature dependence of C′ are found to be due to the strong magnetochemical coupling in the DO3 phase.
Reliability of ion accumulation and growth components for selecting salt tolerant lines in large populations of rice
Authors: Ul Haq Tanveer , Akhtar Javaid , Steele Katherine A. , Munns Rana , Gorham John
Published: December 2013

Ion accumulation and growth under salt stress was studied in two experiments in a rice mapping population derived from parents CO39 and Moroberekan with 4-fold differences in shoot Na+ accumulation. The 120 recombinant inbred lines (RILs) had differences up to 100-fold in Na+. Measurement of ‘salt tolerance’ (biomass production of the RILs in 100 mM NaCl relative to controls) after 42 days showed a 2-fold variation in ‘salt tolerance’ between parents, with five RILs being more tolerant than the more tolerant parent CO39. The reliability of various traits for selecting salt tolerance in large populations was explored by measuring Na+, K+ and K+/Na+ ratios in leaf blades and sheaths after 7 or 21 days of exposure to 100 mM NaCl, and their correlation with various growth components and with leaf injury. The highest correlations were found for Na+ in the leaf blade on day 21 with injury at day 42 in both experiments (r = 0.7). Earlier measurements of Na+ or of injury had lower correlations. The most sensitive growth components were tiller number plant–1 and shoot water content (g water g–1 dry weight), and these were correlated significantly with Na+ and, to a lesser extent, with K+/Na+. These studies showed that exposure for at least 42 days may be needed to clearly demonstrate the beneficial effect of the trait for Na+ exclusion on growth under salinity.
Impacts of extreme weather on the health and well-being of people who are homeless
Authors: Pendrey Catherine G. A. , Carey Marion , Stanley Janet
Published: December 2013

This letter responds to the article by Cusack et al., ‘Extreme weather-related health needs of people who are homeless’ (Australian Journal of Primary Health, 2013, 19(3), 250–255), which addressed the impacts of extreme weather on the health of the homeless population in inner city Adelaide. We compare the findings of Cusack et al. to our own original research, based on interviews with service providers to the homeless in urban and rural Victoria. We further place this issue in the broader context of climate change, which is crucial given the expected increase in extreme weather events and associated health impacts.
India’s new African horizons: an American perspective
Authors: Pham J. Peter
Published: December 2013

While the extensive network of economic, political, and military ties which the People’s Republic of China has constructed across Africa has been the subject of considerable scrutiny – and, increasingly, not a little alarming – on the part of policy-makers and scholars in both the USA and Europe, the emergence of India as a major player on the continent has, until rather recently, gone largely unnoticed. That is changing, however, as Africa with its energy riches, agricultural potential, and other natural resources as well as its growing population finds itself courted by multiple suitors, both old partners and new. In this context, India’s expanding commercial and strategic engagements across Africa represent a significant move in the global geopolitical order taking shape in the twenty-first century. This paper examines India’s rapidly expanding network of relations, analysing the country’s burgeoning public and private investments in the region as well as its policies vis-à-vis African regional organizations and individual states, especially in the security sector. After briefly reviewing the historic role that India has played in Africa, the study looks at the principal motivations for India’s approach to Africa – including the former’s quests for the resources, business opportunities, diplomatic influence, and security – and Africans’ responses to it. In the context of the broader USA–India strategic partnership as well as American political and security interests in Africa-especially as outlined in the official U.S. Strategy Toward Sub-Saharan Africa, promulgated by the Obama administration in June 2012-the paper argues that India’s willingness to make significant contributions to African peacekeeping and to extend its maritime security cover to the continent’s eastern littoral ought to be welcomed, not least because of the potential positive impact on regional stability and development. Consequently, the author advances the proposition that, while not perfectly aligned, the interests of India and those of USA in Africa are generally complementary and thus there are a number of openings for greater engagement and cooperation between the two countries, a unique opportunity which policy-makers in both countries should be encouraged to seize upon.
South−South cooperation and democracy in Africa: Brazil’s role in Guinea-Bissau
Authors: Abdenur Adriana Erthal , de Souza Neto Danilo Marcondes
Published: December 2013

Over the past decade, Brazilian foreign policy has struggled to balance two principles: respect for national sovereignty and the commitment to promote democracy and human rights both at home and abroad. Understanding how this balancing act affects Brazil’s relations with Africa has become particularly important because Brazilian cooperation with African partners has expanded considerably over the past decade. This article analyzes Brazil’s initiatives in democracy and human rights promotion in the context of Guinea-Bissau. We find that Brazil’s initiatives in this area are channeled through two interconnected venues: multilaterally, especially through the Community of Portuguese-Speaking Countries and the UN Peacebuilding Commission, and bilaterally, through the official technical development cooperation programs coordinated by the Brazilian Cooperation Agency. We argue that, in the case of Guinea-Bissau, Brazil has worked to maintain institution-building as an essential component of development and security efforts to stabilize the country.
Does “rising power” mean “rising donor”? Turkey’s development aid in Africa
Authors: Ozkan Mehmet
Published: December 2013

For each newly emerging donor in Africa, there are different ways of dealing with the continent, different ways of spending aid and prioritizing the problems. At a political and security level, traditional actors are still the major actors in the continent, while economic and development aid is mostly dominated by the newly emerging non-traditional actors. Turkey as a non-traditional actor has been focusing on development aid and economy, but now it has interested in political affairs and state-building too. This has put Turkey in a middle position between traditional and non-traditional actors in the continent. Since 2011, Turkey is interested to be a more political actor in the continent than being merely an economic power or donor country. This certainly has repercussion for the continent and international actors for possible cooperation and coordination. The main focus of this article will be explaining and contextualizing Turkey’s aid involvement in the continent as the main underlying elements of is interest to be a political power in the last few years.
Outbreak of Bloodstream Infections Associated with Multiuse Dialyzers Containing O-Rings
Authors: OYong Kelsey , Marquez Patricia , Terashita Dawn , English L'Tanya , Rivas Hector , Deak Eszter , Mascola Laurene
Published: December 2013

This report details an outbreak investigation conducted by the Los Angeles County Department of Public Health of 3 cases of bacterial infection among patients receiving hemodialysis who were treated at the same dialysis center in 2011. Improper disinfection of reusable dialyzers was hypothesized as the source of transmission.
On Rogers–Ramanujan functions, binary quadratic forms and eta-quotients
Authors: Berkovich Alexander , Yesilyurt Hamza
Published: December 2013

In a handwritten manuscript published with his lost notebook, Ramanujan stated without proofs forty identities for the Rogers–Ramanujan functions. We observe that the function that appears in Ramanujan’s identities can be obtained from a Hecke action on a certain family of eta products. We establish further Hecke-type relations for these functions involving binary quadratic forms. Our observations enable us to find new identities for the Rogers–Ramanujan functions and also to use such identities in return to find identities involving binary quadratic forms.
Ephrin-B2 controls PDGFRβ internalization and signaling
Authors: Nakayama Akiko , Nakayama Masanori , Turner Christopher J. , Höing Susanne , Lepore John J. , Adams Ralf H.
Published: December 2013

B-class ephrins, ligands for EphB receptor tyrosine kinases, are critical regulators of growth and patterning processes in many organs and species. In the endothelium of the developing vasculature, ephrin-B2 controls endothelial sprouting and proliferation, which has been linked to vascular endothelial growth factor (VEGF) receptor endocytosis and signaling. Ephrin-B2 also has essential roles in supporting mural cells (namely, pericytes and vascular smooth muscle cells [VSMCs]), but the underlying mechanism is not understood. Here, we show that ephrin-B2 controls platelet-derived growth factor receptor β (PDGFRβ) distribution in the VSMC plasma membrane, endocytosis, and signaling in a fashion that is highly distinct from its role in the endothelium. Absence of ephrin-B2 in cultured VSMCs led to the redistribution of PDGFRβ from caveolin-positive to clathrin-associated membrane fractions, enhanced PDGF-B-induced PDGFRβ internalization, and augmented downstream mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK) activation but impaired Tiam1–Rac1 signaling and proliferation. Accordingly, mutant mice lacking ephrin-B2 expression in vascular smooth muscle developed vessel wall defects and aortic aneurysms, which were associated with impaired Tiam1 expression and excessive activation of MAP kinase and JNK. Our results establish that ephrin-B2 is an important regulator of PDGFRβ endocytosis and thereby acts as a molecular switch controlling the downstream signaling activity of this receptor in mural cells.
Deregulated origin licensing leads to chromosomal breaks by rereplication of a gapped DNA template
Authors: Neelsen Kai J. , Zanini Isabella M.Y. , Mijic Sofija , Herrador Raquel , Zellweger Ralph , Ray Chaudhuri Arnab , Creavin Kevin D. , Blow J. Julian , Lopes Massimo
Published: December 2013

Deregulated origin licensing and rereplication promote genome instability and tumorigenesis by largely elusive mechanisms. Investigating the consequences of Early mitotic inhibitor 1 (Emi1) depletion in human cells, previously associated with rereplication, we show by DNA fiber labeling that origin reactivation occurs rapidly, well before accumulation of cells with >4N DNA, and is associated with checkpoint-blind ssDNA gaps and replication fork reversal. Massive RPA chromatin loading, formation of small chromosomal fragments, and checkpoint activation occur only later, once cells complete bulk DNA replication. We propose that deregulated origin firing leads to undetected discontinuities on newly replicated DNA, which ultimately cause breakage of rereplicating forks.
Fbw7 dimerization determines the specificity and robustness of substrate degradation
Authors: Welcker Markus , Larimore Elizabeth A. , Swanger Jherek , Bengoechea-Alonso Maria T. , Grim Jonathan E. , Ericsson Johan , Zheng Ning , Clurman Bruce E.
Published: December 2013

The Fbw7 tumor suppressor targets a broad network of proteins for ubiquitylation. Here we show critical functions for Fbw7 dimerization in regulating the specificity and robustness of degradation. Dimerization enables Fbw7 to target substrates through concerted binding to two suboptimal and independent recognition sites. Accordingly, an endogenous dimerization-deficient Fbw7 mutation stabilizes suboptimal substrates. Dimerization increases Fbw7's robustness by preserving its function in the setting of mutations that disable Fbw7 monomers, thereby buffering against pathogenic mutations. Finally, dimerization regulates Fbw7 stability, and this likely involves Fbw7 trans-autoubiquitylation. Our study reveals novel functions of Fbw7 dimerization and an unanticipated complexity in substrate degradation.
MAPK Hog1 closes the S. cerevisiae glycerol channel Fps1 by phosphorylating and displacing its positive regulators
Authors: Lee Jongmin , Reiter Wolfgang , Dohnal Ilse , Gregori Christa , Beese-Sims Sara , Kuchler Karl , Ammerer Gustav , Levin David E.
Published: December 2013

The aquaglyceroprin Fps1 is responsible for glycerol transport in yeast in response to changes in extracellular osmolarity. Control of Fps1 channel activity in response to hyperosmotic shock involves a redundant pair of regulators, Rgc1 (regulator of the glycerol channel 1) and Rgc2, and the MAPK Hog1 (high-osmolarity glycerol response 1). However, the mechanism by which these factors influence channel activity is unknown. We show that Rgc2 maintains Fps1 in the open channel state in the absence of osmotic stress by binding to its C-terminal cytoplasmic domain. This interaction involves a tripartite pleckstrin homology (PH) domain within Rgc2 and a partial PH domain within Fps1. Activation of Hog1 in response to hyperosmotic shock induces the rapid eviction of Rgc2 from Fps1 and consequent channel closure. Hog1 was recruited to the N-terminal cytoplasmic domain of Fps1, which it uses as a platform from which to multiply phosphorylate Rgc2. Thus, these results reveal the mechanism by which Hog1 regulates Fps1 in response to hyperosmotic shock.
Combining Ca2+ and Membrane Potential Imaging in Single Neurons
Authors: Canepari Marco , Vogt Kaspar E. , De Waard Michel , Zecevic Dejan
Published: December 2013

The ability to monitor Ca2+ signals and membrane potential simultaneously at multiple locations on the same neuron facilitates further progress in our understanding of neuronal function. In particular, this method allows correlation of electrical and chemical signals from multiple sites, including those inaccessible to microelectrodes. This protocol describes a procedure for loading cells with two indicators, a Ca2+-sensitive Fura dye and voltage-sensitive JPW1114, together with the equipment required for detecting and imaging the two signals. Potential problems are discussed as well as the capabilities and limitations of the technique.
Combining Ca2+ Imaging with ʟ-Glutamate Photorelease
Authors: Canepari Marco , De Waard Michel , Ogden David
Published: December 2013

This article describes simple configurations and methods for measuring optical Ca2+ signals in response to photorelease of ʟ-glutamate. This photostimulation allows activation of postsynaptic glutamate receptors without activation of voltage-gated Ca2+ channels, thereby permitting the separation and analysis of different Ca2+ components. We give details of basic microscopy configurations and recommend tools for efficiently illuminating the preparation while preserving the healthy condition of the tissue. We also suggest methodological procedures and discuss linear optics for achieving simultaneous imaging and uncaging using two-photon illumination.
RNA Sequencing by Primer Extension
Authors: Nilsen Timothy W.
Published: December 2013

Direct sequencing of RNA by primer extension is a fast and accurate method that is useful in a variety of situations. It is a valuable technique for determining the faithfulness of in vitro processing reactions, such as splicing or RNA editing. It is often used as an alternative to reverse transcription PCR (RT–PCR) followed by cloning and DNA sequencing. In the primer extension reaction, a radiolabeled probe (almost always a 5′-end-labeled DNA oligonucleotide) is annealed to the target RNA of interest. After hybridization, cDNA synthesis by reverse transcription proceeds from the 3′ end of the primer in the presence of chain-terminating dideoxynucleotide triphosphates. The cDNA products are fractionated on denaturing polyacrylamide gels and analyzed by phosphorimaging or autoradiography.
Infrared Video Microscopy for Visualizing Neurons and Neuronal Excitation in Brain Slices
Authors: Dodt Hans-Ulrich , Becker Klaus , Zieglgänsberger Walter
Published: December 2013

Here we describe methods for imaging neurons and neuronal excitation in brain slices with infrared video microscopy. Patch clamping in conjunction with a gradient-contrast system allows electrical recording from fine neuronal processes. Imaging with an infrared (IR)-darkfield system allows visualization of the intrinsic optical signal (IOS).
Making Mosaic Fish Primordia by Focal Electroporation
Authors: Schuster Kevin , Ghysen Alain
Published: December 2013

The lateral line is a mechanosensory system that comprises a set of discrete sense organs called neuromasts, which are arranged in reproducible patterns on the surface of fish and amphibians. The posterior component of the system, the posterior lateral line (PLL), comprises the neuromasts on the body and tail. It develops from the migrating primordium and so can be used to examine various aspects of neural development, including the control of long-range, collective cell migration and the mechanisms underlying the establishment of appropriate connectivity. Mosaic animals are those in which one or a few cells differ genetically from all others. Several methods have been developed to generate mosaic zebrafish, which can be used in long-term fate mapping or lineage tracing experiments if the progenitor cell stably expresses a reporter gene such as green fluorescent protein. Mosaic analysis can also be used to evaluate the cell autonomy of a given mutation, confronting mutant and wild-type cells, or two different types of mutant cells, in morphogenetic mosaics. Here we present an application of electroporation, which is designed to generate mosaics in defined parts of the developing zebrafish PLL. The method is based on the idea of focal electroporation, a technique developed to introduce dyes and constructs into cells within intact tissues. Current is forced into the embryo by sealing the tip of the electrode against the enveloping cells (periderm or ectoderm depending on the developmental stage, or mantle cells in the case of neuromasts).
Combining Calcium Imaging with Other Optical Techniques
Authors: Canepari Marco , Zecevic Dejan , Vogt Kaspar E. , Ogden David , De Waard Michel
Published: December 2013

Ca2+ imaging is a commonly used approach for measuring Ca2+ signals at high spatial resolution. The method is often combined with electrode recordings to correlate electrical and chemical signals or to investigate Ca2+ signals following an electrical stimulation. To obtain information on electrical activity at the same spatial resolution, Ca2+ imaging must be combined with membrane potential imaging. Similarly, stimulation of subcellular compartments requires photostimulation. Thus, combining Ca2+ imaging with an additional optical technique facilitates the study of a number of physiological questions. The aim of this article is to introduce some basic principles regarding the combination of Ca2+ imaging with other optical techniques. We discuss the design of the optics, the design of experimental protocols, the optical characteristics of Ca2+ indicators used in combination with an optical probe, and the affinity of the Ca2+ indicator in relation to the type of measurement. This information will enable the reader to devise an optimal strategy for combined optical experiments.
Spatial Light Modulator Microscopy
Authors: Nikolenko Volodymyr , Peterka Darcy S. , Araya Roberto , Woodruff Alan , Yuste Rafael
Published: December 2013

The use of spatial light modulators (SLMs) for two-photon laser microscopy is described. SLM phase modulation can be used to generate nearly any spatiotemporal pattern of light, enabling simultaneous illumination of any number of selected regions of interest. We take advantage of this flexibility to perform fast two-photon imaging or uncaging experiments on dendritic spines and neocortical neurons. By operating in the spatial Fourier plane, an SLM can effectively mimic any arbitrary optical transfer function and thus replace, in software, many of the functions provided by hardware in standard microscopes, such as focusing, magnification, and aberration correction.
Liquid X-ray scattering with a pink-spectrum undulator
Authors: Bratos S. , Leicknam J.-Cl. , Wulff M. , Khakhulin D.
Published: December 2013

X-ray scattering from a liquid using the spectrum from the undulator fundamental is examined as a function of the bandwidth of the spectrum. The synchrotron-generated X-ray spectrum from an undulator is `pink',i.e.quasi-monochromatic but having a saw-tooth-shaped spectrum with a bandwidth from 1 to 15%. It is shown that features inS(q) are slightly shifted and dampened compared with strictly monochromatic data. In return, the gain in intensity is 250–500 which makes pink beams very important for time-resolved experiments. The undulator spectrum is described by a single exponential with a low-energy tail. The tail shifts features in the scattering function towards high angles and generates a small reduction in amplitude. The theoretical conclusions are compared with experiments. Ther-resolved Fourier transformed signals are discussed next. Passing fromq- tor-space requires a sin-Fourier transform. The Warren convergence factor is introduced in this calculation to suppress oscillatory artifacts from the finiteqMin the data. It is shown that the deformation ofr-resolved signals from the pink spectrum is small compared with that due to the Warren factor. Theq-resolved and ther-resolved pink signals thus behave very differently.
Smooth bark surfaces can defend trees against insect attack: resurrecting a ‘slippery’ hypothesis
Authors: Ferrenberg Scott , Mitton Jeffry B.
Published: December 2013

Smooth bark on trees and shrubs was historically hypothesized to be an anatomical defence against epiphytic vegetation and phytophagous insects. This hypothesis has fallen from favour, yet no clear tests of bark texture as a defence against insects have been published.

We tested the smooth bark defence hypothesis using bark beetles specialized in attacking pine trees as model insects, andPinus flexilis(limber pine) – a widespread tree that can have both smooth and rough bark surfaces on the same stem – as the model tree. We investigated the effects of bark texture on the locations of bark beetle attacks on trees with a combination of field surveys and experiments in the Colorado Rocky Mountains, USA.

Bark beetle attacks were overwhelmingly located on rough bark surfaces and virtually absent from smooth bark. Increasing proportional coverage by smooth bark was negatively related to bark beetle attacks per square metre of bark surface. Experimental tests of bark beetles' ability to grip smooth versus rough bark revealed that bark beetles have difficulty gripping and quickly fell from smooth bark but not from rough bark.

Smooth bark was negatively related to increasing tree size, but our models indicated that even partial coverage by smooth bark on a tree's trunk can significantly reduce total bark beetle attacks – this reduction likely improves tree fitness as bark beetles must aggregate to overcome tree defences.

Synthesis. Our results indicate that smooth bark on trees can act as an anatomical defence against insects by reducing their ability to grip a tree's surface – even for insects specialized in attacking tree stems. Similar to other forms of anti‐insect defence (i.e. secondary chemistry, leaf toughness), smooth bark appears to be influenced by plant ontogeny whereby younger trees have greater defences than older trees. Understanding the adaptive significance of bark texture will require continued field and genetic study. Nevertheless, our results revealed that smooth bark texture increases tree resistance to phytophagous insects calling for the resurrection and vetting of the smooth bark defence hypothesis.
Supermax Prisons
Authors: Mears Daniel P.
Published: December 2013

Research Summary

Supermaximum‐security prisons—or “supermaxes”—symbolize the “get tough” criminal justice policies that have developed over the past three decades in the United States and in other countries. Proponents believe that they effectively address critical prison system problems; opponents believe that they do not and that they create substantial harm. This essay examines the available evidence about supermaxes.

Policy Implications

A range of considerations are relevant to determining whether supermaxes constitute effective policy. These include (a) definitional problems in discussing supermax incarceration; (b) five critical dimensions along which evidence for policies is desirable and along which supermaxes fall short, including demonstration of policy need, credible policy theory, high‐quality implementation, impact, and benefits that exceed costs and do so more than other policies; (c) the challenge of assessing causal claims related to supermaxes; (d) legal and ethical issues; (e) policy and political challenges confronting states; (f) policy options other than supermaxes; and (g) research gaps that remain to be addressed. The essay argues that causal uncertainty about supermax incarceration makes it difficult at present to claim credibly that it achieves intended goals. Policy implications and recommendations are discussed.
Public Private Partnership and Development from the Bottom Up–From Failing to Scaling
Authors: Simon John , Schellekens Onno , de Groot Arie
Published: December 2013

The aid model for development is broken. It has failed to deliver meaningful progress in developing countries across a wide range of development indicators. Moreover, the model is now constrained by the fiscal realities of the major donors. Its failure is a function of ignoring the institutions, formal and informal, and incentives that often work at cross purposes to donors when the state is not functioning properly. A model that recognizes and builds on the existing, often local, institutional relationships in poor countries through public private partnerships (PPPs) offers renewed possibilities for success. PPPs can create trust through enforcing existing and newly created local institutions from the bottom up and lower investment risks by using donor money as a lever to mobilize private loans and investments. These mechanisms will support economic exchange, the source of development. This paper discusses the origins of this model, the different forms it can take, and the challenges it faces.
Four Models of Interest Mediation in Global Environmental Governance
Authors: Gale Fred
Published: December 2013

Negotiating global environmental agreements involves aggregating and mediating divergent interests. In multiparty electoral systems, the process begins at the subnational level where interests aggregated by business associations, trade unions and civil society organizations are represented to political parties and governments in an effort to secure better (from their perspective) policy outcomes. How domestic political systems aggregate, represent and mediate diverse competing interests is a key question within comparative politics with some analysts favouring pluralism and others defending corporatist and policy network arrangements. This rich domestic literature has no global equivalent, due to the dominance until recently of intergovernmental forms of interest mediation at the global level. The rise of sector‐specific global governance organizations such as the Forest Stewardship Council suggests it is timely to investigate the different arrangements being used to mediate global interests and derive some hypotheses about how these shape global politics and policy. Using a grounded theory approach, this article compares and contrasts four different global interest mediation arrangements: intergovernmental (UNForum on Forests (UNFF)), single‐interest (Responsible Care (RC)), multistakeholder (Marine Stewardship Council (MSC)) and corporatist (Forest Stewardship Council (FSC)).
Genome‐wide DNA methylation changes with age in disease‐free human skeletal muscle
Authors: Zykovich Artem , Hubbard Alan , Flynn James M. , Tarnopolsky Mark , Fraga Mario F. , Kerksick Chad , Ogborn Dan , MacNeil Lauren , Mooney Sean D. , Melov Simon
Published: December 2013

A decline in skeletal muscle mass and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report for the first time a genome‐wide study of DNA methylation dynamics in skeletal muscle of healthy male individuals during normal human aging. We predominantly observed hypermethylation throughout the genome within the aged group as compared to the young subjects. Differentially methylated CpG (dmCpG) nucleotides tend to arise intragenically and are underrepresented in promoters and are overrepresented in the middle and 3′ end of genes. The intragenic methylation changes are overrepresented in genes that guide the formation of the junction of the motor neuron and myofibers. We report a low level of correlation of gene expression from previous studies of aged muscle with our current analysis of DNA methylation status. For those genes that had both changes in methylation and gene expression with age, we observed a reverse correlation, with the exception of intragenic hypermethylated genes that were correlated with an increased gene expression. We suggest that a minimal number of dmCpG sites or select sites are required to be altered in order to correlate with gene expression changes. Finally, we identified 500 dmCpG sites that perform well in discriminating young from old samples. Our findings highlight epigenetic links between aging postmitotic skeletal muscle and DNA methylation.
Downregulation of the Werner syndrome protein induces a metabolic shift that compromises redox homeostasis and limits proliferation of cancer cells
Authors: Li Baomin , Iglesias‐Pedraz Juan Manuel , Chen Leng‐Ying , Yin Fei , Cadenas Enrique , Reddy Sita , Comai Lucio
Published: December 2013

The Werner syndrome protein (WRN) is a nuclear protein required for cell growth and proliferation. Loss‐of‐function mutations in the Werner syndrome gene are associated with the premature onset of age‐related diseases. How loss of WRN limits cell proliferation and induces replicative senescence is poorly understood. Here, we show that WRN depletion leads to a striking metabolic shift that coordinately weakens the pathways that generate reducing equivalents for detoxification of reactive oxygen species and increases mitochondrial respiration. In cancer cells, this metabolic shift counteracts the Warburg effect, a defining characteristic of many malignant cells, resulting in altered redox balance and accumulation of oxidative DNA damage that inhibits cell proliferation and induces a senescence‐like phenotype. Consistent with these findings, supplementation with antioxidant rescues at least in part cell proliferation and decreases senescence in WRN‐knockdown cancer cells. These results demonstrate that WRN plays a critical role in cancer cell proliferation by contributing to the Warburg effect and preventing metabolic stress.
Pathological risk factors in upper urinary tract cancer
Authors: Shimamoto Tsutomu , Inoue Keiji , Kamata Masayuki , Kuno Takahira , Karashima Takashi , Shuin Taro
Published: December 2013

Aims

To evaluate pathological factors for prognosis, intravesical recurrence and distant metastasis of upper urinary tract cancer.

Methods

This clinical study included 105 patients with renal pelvic and ureteral cancer who were treated at the Kochi Medical School Hospital between 1982 and 2008. Of these patients, 90 who underwent nephroureterectomy were analyzed for pathological risk factors using uni‐ and multivariate analysis.

Results

The mean follow‐up period of the 105 patients was 53 months. The disease‐specific survival rates were 70% and 62% at 3 and 5 years. Twenty‐three patients (23%) developed intravesical recurrence, and the mean and median times to recurrence were 18.8 and 9.2 months, respectively. Seventeen patients (19%) had distant metastasis, and the mean and median times to distant metastasis were 25.2 and 25.3 months, respectively. Multivariate analysis identified the pathological grade as an independent risk factor for prognosis (P = 0.031), age (≥67 years) and tumor diameter (≥3 cm) as independent risk factors for intravesical recurrence (P = 0.007 and 0.003, respectively), and the pathological grade (G1,2 vs G3) and lymphatic invasion as independent risk factors for distant metastasis (P = 0.006 and 0.003, respectively).

Conclusion

Patients with higher‐grade upper urinary tract cancer show a poor prognosis, and often develop distant metastasis, suggesting the need for careful postoperative follow‐up. Those with lymphatic invasion or tumors of 3 cm or more in diameter frequently develop intravesical recurrence and distant metastasis, respectively, indicating the need for strict follow‐up.
The prognosis of patients with lung cancer admitted to the medical intensive care unit
Authors: Hwang Ki‐Eun , Seol Chang‐Hwan , Hwang Yu‐Ri , Jo Hoon‐Gil , Park Seong‐Hoon , Yoon Kwon‐Ha , Park Do‐Sim , Jeong Eun‐Taik , Kim Hak‐Ryul
Published: December 2013

Aims

Lung cancer remains the leading cause of cancer mortality worldwide. Despite their poor prognosis, patients with lung cancer are increasingly being admitted to the medical intensive care unit (MICU) for treatment of critical illnesses. The aim of this study was to assess the outcome of patients with lung cancer who are admitted to an MICU and to identify the measurable predictors of their MICU outcome.

Methods

We conducted retrospective analysis on 97 patients with lung cancer admitted to the MICU between 2007 and 2011.

Results

The mean age ± standard deviation was 71.8 ± 6.8 years. Of the 97 patients (82 male), 73 patients (75%) had non‐small cell lung cancer stage IIIB, IV and 24 patients (25%) had small cell lung cancer. The intensive care unit mortality and in‐hospital mortality rates were 53.6 and 61.8%. The main reasons for MICU admission were pneumonia (n = 51) and complication of cancer management (n = 45). The predictors of poor MICU outcome were history of diabetes mellitus (P = 0.028), Acute Physiology and Chronic Health Evaluation II score (P = 0.018), need for mechanical ventilation (P = 0.014), use of vasoactive agents (P < 0.0001), the presence of acute renal failure (P < 0.0001) and presence of multiorgan failure (P < 0.0001).

Conclusions

We found that in‐hospital mortality was not influenced by age, sex or performance status score of patients with lung cancer but increased with the severity of organ failure at MICU admission.
Surgical resection and long‐term survival outcome for non‐small cell lung cancer: A comparison of Victorian population‐based studies spanning a decade
Authors: Wright Gavin M , Thursfield Vicky J , Ball David L , Richardson Gary E , Irving Louis , Giles Graham G , Mitchell Paul
Published: December 2013

Aim

A survey of management of lung cancer diagnosed in Victoria in 2003 was commissioned by the Victorian Cooperative Oncology Group to identify gaps in the management of this disease. Results from a similar survey in 1993 were available to identify differences in the disease, management and outcomes. This paper details results of the surgically managed subset within the larger study.

Methods

All patients diagnosed with lung cancer in the first 6 months of 2003 were identified from the Victorian Cancer Registry. Registry research staff completed a detailed questionnaire using primary source documents from hospitals and consulting rooms. The survey data were then de‐identified with respect to patient and treating clinician prior to statistical analysis by the investigators.

Results

From eligible cases identified, non‐small cell lung cancer was confirmed in 655 cases with a minimum of 6 years of follow‐up. Thoracotomy was performed in 145 cases (22%), but only 130 received the intended resection. Compared with 1993, significant differences were increased use of preoperative positron emission tomography (PET) scanning (79% vs 0%), relatively fewer resections (20% vs 25%), lower pneumonectomy rate (14% vs 25%) and higher sub‐lobar resection rate (22% vs 11%). The 30‐day mortality remained below 2%. Positive resection margin (21%) and abandoned resection rates (10%) were much higher than expected. Overall 5‐year survival was 42%, unchanged from 1993.

Conclusion

Irrespective of widespread introduction of PET scanning, thoracotomy without resection was common. While operative mortality and overall survival were well within benchmark standards, futile thoracotomy and positive resection margin rates were unacceptably high.
Is Colposcopy necessary at twelve months after large loop excision of the transformation zone? A clinical audit
Authors: Thompson Valerie , Marin Raymond
Published: December 2013

Objective

The purpose of this study was to review outcomes from LLETZ (large loop excision of the transformation zone) procedures carried out for high‐grade cervical intraepithelial neoplasia (CIN), in particular findings at colposcopy, cytology and HR‐HPV(high‐risk human papilloma virus) result to assess whether colposcopy provides any additional information in the management of women at 12 months.

Methods

We retrospectively analysed 252 patients who had a LLETZ procedure for a HSIL (high‐grade squamous intraepithelial lesion) between January 2005 and December 2010.

Results

Eighty per cent of women who had a LLETZ procedure for HSIL were reviewed in our colposcopy clinic at 12 months after the procedure. Colposcopy at 12 months after LLETZ was documented as unsatisfactory for 30% of these women. The sensitivity of colposcopy at 12 months after LLETZ was 0.47, and the specificity was 0.95.

Conclusion

Colposcopy examination is an insensitive tool for detection of persisting HPV‐related change after excision of high‐grade CIN. Its usefulness to investigate persistent or recurrent HSIL is further reduced by the high rate of unsatisfactory colposcopy examinations after a LLETZ procedure. Papanicolaou smear and HRHPV tests may be adequate follow‐up at 12 months after LLETZ for women at low risk of recurrence of HSIL.
Carers' express positive views on the acceptability, efficacy and safety of buccal midazolam for paediatric status epilepticus
Authors: Khan Arif , Baheerathan Aravindhan , Setty Gururaj , Hussain Nahin
Published: December 2013

Aim

Buccal midazolam has emerged as an effective alternative to rectal diazepam in the management of paediatric status epilepticus. This study aimed to identify carers' views on the safety, efficacy and acceptability of buccal midazolam in the management of this common neurological emergency.

Methods

Community‐based, face‐to‐face interviews were carried out with 34 carers to evaluate the effectiveness, adverse effects and convenience of buccal midazolam as a rescue treatment for prolonged seizures. All children received 2.5 to 10 mg of Epistatus, a proprietary oral solution (10 mg/mL). We evaluated therapeutic success, time taken for seizures to cease and the need to attend the emergency department, together with the development of side effects, namely respiratory depression and sedation.

Results

Most of the families (91%) found that buccal midazolam was always, or usually, effective in stopping seizures and it prevented hospital admission in 65% of cases. The majority (96%) of those who had used both buccal midazolam and rectal diazepam preferred the former as it was easier to administer, more socially acceptable and did not sedate the child as much.

Conclusion

Carers felt that buccal midazolam was an effective, safe and more acceptable alternative to rectal diazepam in the management of paediatric status epilepticus.
A pilot randomized controlled trial to increase smoking cessation by maintaining National Health Service Stop Smoking Service attendance
Authors: Matcham Faith , McNally Lisa , Vogt Florian
Published: December 2013

Objectives

TheNational Health Service (NHS) Stop Smoking Service (SSS) is an extremely cost‐effective method of enabling smoking cessation. However, theSSSis only used by a minority of smokers. Developing interventions to maintain service attendance may help to increase the number of quitters. This study pilots an intervention aimed at maintaining attendance by (1) increasing motivation to attend through a booklet providing evidence of service effectiveness and (2) strengthening the link between motivation to attend and attendance through forming an implementation intention.

Design

A factorial randomized controlled trial.

Methods

A total of 160 newly enrolled smokers at the SurreyNHS SSSwere recruited and randomly assigned to one of four conditions: (1) standard care (SC), (2)SC + effectiveness booklet, (3)SC + implementation intention, and (4)SC + effectiveness booklet + implementation intention. The outcome measures included attendance at theSSSand the 4‐week quit rate.

Results

The booklet increased service attendance (OR = 2.93,p < .01, 95%CI = 1.45–5.93; Number Needed to Treat = 3.3) but had no impact on the 4‐week quit rate (OR = 1.55, 95%CI = 0.75–3.21). Forming an implementation intention had no impact on service attendance or the 4‐week quit rate. Attending the service was associated with a higher 4‐week quit rate (ρ = 87.52,p < .001).

Conclusions

Presenting information about the effectiveness of the service improved service attendance. A larger trial now needs to evaluate whether this intervention can also increase the quit rate.

Statement of contribution

What is already known on this subject?TheNHSStop Smoking Service is an effective yet underused method of enabling smoking cessation. Low uptake levels may be due to smokers’ misconception that the service will not improve their chances of quitting successfully. Improving smokers’ perceptions of service efficacy may be valuable for maintaining service attendance, and subsequently improving smoking cessation levels in theUnited Kingdom.

What does this study add?

This pilot randomized controlled trial is the first to target service attendance rather than cessation levels.

The results demonstrate that providing evidence of service efficacy in a simple icon array format can significantly improve service attendance.
Structure‐Based Evaluation of C5 Derivatives in the Catechol Diether Series Targeting HIV‐1 Reverse Transcriptase
Authors: Frey Kathleen M. , Gray William T. , Spasov Krasimir A. , Bollini Mariela , Gallardo‐Macias Ricardo , Jorgensen William L. , Anderson Karen S.
Published: December 2013

Using a computationally driven approach, a class of inhibitors with picomolar potency known as the catechol diethers were developed targeting the non‐nucleoside‐binding pocket of HIV‐1 reverse transcriptase. Computational studies suggested that halogen‐bonding interactions between the C5 substituent of the inhibitor and backbone carbonyl of conserved residue Pro95 might be important. While the recently reported crystal structures of the reverse transcriptase complexes confirmed the interactions with the non‐nucleoside‐binding pocket, they revealed the lack of a halogen‐bonding interaction with Pro95. To understand the effects of substituents at the C5 position, we determined additional crystal structures with 5‐Br and 5‐H derivatives. Using comparative structural analysis, we identified several conformations of the ethoxy uracil dependent on the strength of a van der Waals interaction with the Cγ of Pro95 and the C5 substitution. The 5‐Cl and 5‐F derivatives position the ethoxy uracil to make more hydrogen bonds, whereas the larger 5‐Br and smaller 5‐H position the ethoxy uracil to make fewer hydrogen bonds. EC50 values correlate with the trends observed in the crystal structures. The influence of C5 substitutions on the ethoxy uracil conformation may have strategic value, as future derivatives can possibly be modulated to gain additional hydrogen‐bonding interactions with resistant variants of reverse transcriptase.