bluuebunny/crossref_metadata_2025 huggingface dataset:
Innate interferons inhibit allergen and microbial specific TH2 responses
Authors: Pritchard Antonia L , White Olivia J , Burel Julie G , Upham John W
Published: July 2012

Several studies provided evidence of innate interferons (IFNs) regulating TH2 cytokine production using purified CD4+ memory cells and TH2 polarisation via interleukin‐4 (IL‐4). Vitally, none of these previous studies examined IFN attenuation of TH2 responses to allergen or antigen. This study therefore sought to investigate the abrogation of specific allergen‐ and antigen‐stimulated TH2 response in peripheral blood mononuclear cells (PBMC) derived from 12 sensitised individuals by IFN‐β and IFN‐λ. PBMC were cultured in the presence of house dust mite (HDM) allergen, rhinovirus (RV), influenza vaccine and tetanus toxoid (TT)±either IFN‐β or IFN‐λ for 3 and 5 days. IFN‐γ, IL‐5 and IL‐13 protein levels were measured by ELISA. Quantitative PCR (qPCR) was used to investigate induction of genes involved in control of TH2 cytokines. No alteration in TH1 IFN‐γ allergen/antigen response was observed with addition of IFN‐β or IFN‐λ. Consistent abrogation of TH2 response to HDM and influenza was observed with IFN‐β at both time points; attenuation was observed by day 5 with RV and TT. IFN‐λ had no consistent effect on TH2 production except in the presence of RV (multiplicity of infection=5); a decrease in IL‐5 alone was observed in the presence of trivalent inactivated influenza vaccine. GATA binding protein 3 (GATA3) and suppressors of cytokine signalling3 mRNA were differentially regulated in HDM and influenza‐stimulated cultures±IFN‐β. We concluded that IFN‐β produced a strong and consistent abrogation of TH2 cytokine production in the presence of a range of allergen and antigen stimulants.
Structural origin of polymorphism of Alzheimer's amyloid β-fibrils
Authors: Agopian Audrey , Guo Zhefeng
Published: July 2012

Formation of senile plaques containing amyloid fibrils of Aβ (amyloid β-peptide) is a pathological hallmark of Alzheimer's disease. Unlike globular proteins, which fold into unique structures, the fibrils of Aβ and other amyloid proteins often contain multiple polymorphs. Polymorphism of amyloid fibrils leads to different toxicity in amyloid diseases and may be the basis for prion strains, but the structural origin for fibril polymorphism is still elusive. In the present study we investigate the structural origin of two major fibril polymorphs of Aβ40: an untwisted polymorph formed under agitated conditions and a twisted polymorph formed under quiescent conditions. Using electron paramagnetic resonance spectroscopy, we studied the inter-strand side-chain interactions at 14 spin-labelled positions in the Aβ40 sequence. The results of the present study show that the agitated fibrils have stronger inter-strand spin–spin interactions at most of the residue positions investigated. The two hydrophobic regions at residues 17–20 and 31–36 have the strongest interactions in agitated fibrils. Distance estimates on the basis of the spin exchange frequencies suggest that inter-strand distances at residues 17, 20, 32, 34 and 36 in agitated fibrils are approximately 0.2 Å (1 Å=0.1 nm) closer than in quiescent fibrils. We propose that the strength of inter-strand side-chain interactions determines the degree of β-sheet twist, which then leads to the different association patterns between different cross β-units and thus distinct fibril morphologies. Therefore the inter-strand side-chain interaction may be a structural origin for fibril polymorphism in Aβ and other amyloid proteins.
Angiotensin II AT1 receptor blockers as treatments for inflammatory brain disorders
Authors: Saavedra Juan M.
Published: July 2012

The effects of brain AngII (angiotensin II) depend on AT1 receptor (AngII type 1 receptor) stimulation and include regulation of cerebrovascular flow, autonomic and hormonal systems, stress, innate immune response and behaviour. Excessive brain AT1 receptor activity associates with hypertension and heart failure, brain ischaemia, abnormal stress responses, blood–brain barrier breakdown and inflammation. These are risk factors leading to neuronal injury, the incidence and progression of neurodegerative, mood and traumatic brain disorders, and cognitive decline. In rodents, ARBs (AT1 receptor blockers) ameliorate stress-induced disorders, anxiety and depression, protect cerebral blood flow during stroke, decrease brain inflammation and amyloid-β neurotoxicity and reduce traumatic brain injury. Direct anti-inflammatory protective effects, demonstrated in cultured microglia, cerebrovascular endothelial cells, neurons and human circulating monocytes, may result not only in AT1 receptor blockade, but also from PPARγ (peroxisome-proliferator-activated receptor γ) stimulation. Controlled clinical studies indicate that ARBs protect cognition after stroke and during aging, and cohort analyses reveal that these compounds significantly reduce the incidence and progression of Alzheimer's disease. ARBs are commonly used for the therapy of hypertension, diabetes and stroke, but have not been studied in the context of neurodegenerative, mood or traumatic brain disorders, conditions lacking effective therapy. These compounds are well-tolerated pleiotropic neuroprotective agents with additional beneficial cardiovascular and metabolic profiles, and their use in central nervous system disorders offers a novel therapeutic approach of immediate translational value. ARBs should be tested for the prevention and therapy of neurodegenerative disorders, in particular Alzheimer's disease, affective disorders, such as co-morbid cardiovascular disease and depression, and traumatic brain injury.
Perspectives of High Tech Augmentative and Alternative Communication Users With Cerebral Palsy at the Post-Secondary Level
Authors: Chung Yoosun , Behrmann Michael , Bannan Brenda , Thorp Eva
Published: July 2012

In this qualitative case study, we investigated the perspectives of users of high tech augmentative and alternative communication (AAC) systems regarding their AAC systems, suggestions for others, and their successes and barriers. The five participants in this study had cerebral palsy and were at the postsecondary education level or the employment status. We found 5 main themes during the investigation: (a) day-to-day challenges; (b) experiences with AAC; (c) perceptions of preferable features and future AAC; (d) suggestions to others, including communication partners, professionals in the AAC field, and/or potential AAC users; and (e) adopted strategies. We will interpret these findings from three perspectives: (a) the participants' perspectives on AAC; (b) their perspectives on other people; and (c) their personal insights on themselves. Overall, participants indicated that AAC systems were indispensable in their daily lives, school settings, and work environments. However, all of the participants preferred to use their natural speech if possible, and thought that their AAC device was not a replacement for speech. Rather, they perceived their AAC device as a tool for useful and flexible communication.
Administration: Opportunities for Enhanced Clinical Experience Through Regional Stewardship
Authors: Kleinhans Kelly A. , Hart Sharon B.
Published: July 2012

Understanding the community in which one practices is equally important to the clinical skills and applications of knowledge acquired by a graduate student in speech-language pathology in clinical settings. Shifting political and economic landscapes that are the backdrop for service delivery necessitate that university supervisors help students recognize the influence of local and state community issues. In this article, the authors explain how a service-learning model was used to create a regional outreach activity to benefit stakeholders of a university speech and hearing clinic and members of the regional communities. Specifically, the clinical experience was designed to prepare Kentucky citizens to meet the unique needs of children with Down syndrome and their families.
Diagnostic options for radiative divertor feedback control on NSTX-U
Authors: Soukhanovskii V. A. , Gerhardt S. P. , Kaita R. , McLean A. G. , Raman R.
Published: July 2012

A radiative divertor technique is used in present tokamak experiments and planned for ITER to mitigate high heat loads on divertor plasma-facing components (PFCs) to prevent excessive material erosion and thermal damage. In NSTX, a large spherical tokamak with lithium-coated graphite PFCs and high divertor heat flux (qpeak ⩽ 15 MW/m2), radiative divertor experiments have demonstrated a significant reduction of divertor peak heat flux simultaneously with good core H-mode confinement using pre-programmed D2 or CD4 gas injections. In this work diagnostic options for a new real-time feedback control system for active radiative divertor detachment control in NSTX-U, where steady-state peak divertor heat fluxes are projected to reach 20–30 MW/m2, are discussed. Based on the NSTX divertor detachment measurements and analysis, the control diagnostic signals available for NSTX-U include divertor radiated power, neutral pressure, spectroscopic deuterium recombination signatures, infrared thermography of PFC surfaces, and thermoelectric scrape-off layer current. In addition, spectroscopic “security” monitoring of possible confinement or pedestal degradation is recommended. These signals would be implemented in a digital plasma control system to manage the divertor detachment process via an actuator (impurity gas seeding rate).
Modeling of the ITER-like wide-angle infrared thermography view of JET
Authors: Aumeunier M.-H. , Firdaouss M. , Travère J.-M. , Loarer T. , Gauthier E. , Martin V. , Chabaud D. , Humbert E. ,   JET-EFDA Contributors
Published: July 2012

Infrared (IR) thermography systems are mandatory to ensure safe plasma operation in fusion devices. However, IR measurements are made much more complicated in metallic environment because of the spurious contributions of the reflected fluxes. This paper presents a full predictive photonic simulation able to assess accurately the surface temperature measurement with classical IR thermography from a given plasma scenario and by taking into account the optical properties of PFCs materials. This simulation has been carried out the ITER-like wide angle infrared camera view of JET in comparing with experimental data. The consequences and the effects of the low emissivity and the bidirectional reflectivity distribution function used in the model for the metallic PFCs on the contribution of the reflected flux in the analysis are discussed.
A crossed beam study of 18O(3P)+NO2 and 18O(1D)+NO2: Isotope exchange and O2+NO formation channels
Authors: Mar Kathleen A. , Van Wyngarden Annalise L. , Liang Chi-Wei , Lee Yuan T. , Lin Jim J. , Boering Kristie A.
Published: July 2012

The products and dynamics of the reactions 18O(3P)+NO2 and 18O(1D)+NO2 have been investigated using crossed beams and provide new constraints on the structures and lifetimes of the reactive nitrogen trioxide intermediates formed in collisions of O(3P) and O(1D) with NO2. For each reaction, two product channels are observed – isotope exchange and O2+NO formation. From the measured product signal intensities at collision energies of ∼6 to 9.5 kcal/mol, the branching ratio for O2+NO formation vs. isotope exchange for the O(3P)+NO2 reaction is 52(+6/−2)% to 48(+2/−6)%, while that for O(1D)+NO2 is 97(+2/−12)% to 3(+12/−2)%. The branching ratio for the O(3P)+NO2 reaction derived here is similar to the ratio measured in previous kinetics studies, while this is the first study in which the products of the O(1D)+NO2 reaction have been determined experimentally. Product energy and angular distributions are derived for the O(3P)+NO2 isotope exchange and the O(1D)+NO2→O2+NO reactions. The results demonstrate that the O(3P)+NO2 isotope exchange reaction proceeds by an NO3* complex that is long-lived with respect to its rotational period and suggest that statistical incorporation of the reactant 18O into the product NO2 (apart from zero point energy isotope effects) likely occurs. In contrast, the 18O(1D)+NO2→O2+NO reaction proceeds by a direct “stripping” mechanism via a short-lived 18O-O-NO* complex that results in the occurrence of 18O in the product O2 but not in the product NO. Similarly, 18O is detected in O2 but not NO for the O(3P)+NO2→O2+NO reaction. Thus, even though the product energy and angular distributions for O(3P)+NO2→O2+NO derived from the experimental data are uncertain, these results for isotope labeling under single collision conditions support previous kinetics studies that concluded that this reaction proceeds by an asymmetric 18O-O-NO* intermediate and not by a long-lived symmetric NO3* complex, as earlier bulk isotope labeling experiments had concluded. Applicability of these results to atmospheric chemistry is also discussed.
Vapor-liquid-solid growth of Si nanowires: A kinetic analysis
Authors: Shakthivel Dhayalan , Raghavan Srinivasan
Published: July 2012

A steady state kinetic model has been developed for the vapor-liquid-solid growth of Si whiskers or nanowires from liquid catalyst droplets. The steady state is defined as one in which the net injection rate of Si into the droplet is equal to the ejection rate due to wire growth. Expressions that represent specific mechanisms of injection and ejection of Si atoms from the liquid catalyst droplet have been used and their relative importance has been discussed. The analysis shows that evaporation and reverse reaction rates need to be invoked, apart from just surface cracking of the precursor, in order to make the growth rate radius dependent. When these pathways can be neglected, the growth rate become radius independent and can be used to determine the activation energies for the rate limiting step of heterogeneous precursor decomposition. The ejection rates depend on the mechanism of wire growth at the liquid-solid interface or the liquid-solid-vapor triple phase boundary. It is shown that when wire growth is by nucleation and motion of ledges, a radius dependence of growth rate does not just come from the Gibbs-Thompson effect on supersaturation in the liquid, but also from the dependence of the actual area or length available for nucleation. Growth rates have been calculated using the framework of equations developed and compared with experimental results. The agreement in trends is found to be excellent. The same framework of equations has also been used to account for the diverse pressure and temperature dependence of growth rates reported in the literature.
Application of gauge R&R to the rigorous measurement of quantum yield in fluorescent organic solid state systems
Authors: Green A. P. , Buckley A. R.
Published: July 2012

A rigorous measurement of the photoluminescence quantum yield (PLQY) of three luminescent solid state organic material systems is presented. Poly(9,9-dioctylfluorene), perylene (2.97 M in poly(methyl methacrylate)), and perylene red (0.78 M in poly(methyl methacrylate)), were measured using a Ti:sapphire laser yielding 47 ± 3%, 79 ± 3%, and 51 ± 2%, respectively. A GaN diode laser with differing variability was used to measure the PLQY for perylene and perylene red yielding 71 ± 1% and 53 ± 2%, respectively. Variations due to sample preparation (<0.5%), sample degradation (none), and measurement system repeatability (Ti:sapphire ≈2%, GaN ≈1%) have been determined for each material. Variance in laser intensity is found to be the largest source of error which upon propagation to the PLQY, agrees closely with the uncertainty found by means of the rigorous statistics. This suggests reduction of laser intensity variation could allow much greater precision in absolute determinations of PLQY. Some small systematic bias from calibration and self-absorption corrections cannot be ruled out. The current limit of precision for this measurement is ±1% using the more stable GaN laser though this apparently depends on the material and sample fabrication.
Specified value based defect depth prediction using pulsed thermography
Authors: Zeng Zhi , Tao Ning , Feng Lichun , Zhang Cunlin
Published: July 2012

Several methods have been reported in the literature using pulsed thermography for quantitative measurement of defect depth or sample thickness. In this paper, based on the analysis of a theoretical one-dimensional solution of pulsed thermography, a new method was proposed to first multiply the original temperature decay with square root of the corresponding time to obtain a monotonically increasing function f. A specific time was obtained by setting f equals to a predefined value, the theoretical model shows that the obtained specific time has linear relation with square of defect depth, which was verified with the experimental results of one aluminum and one glass fiber reinforced polymer specimen machined with six flat-bottom wedges as simulated defects. This linearity can be used for defect depth prediction in pulsed thermography.
Atomistic modeling of electron relaxation effect on femtosecond laser-induced thermoelastic response of gold films
Authors: Xiong Q. L. , Tian X. G. , Lu T. J.
Published: July 2012

The thermoelastic response of thin gold films induced by femtosecond laser irradiation is numerically simulated using a modified combined two-temperature model (TTM) and molecular dynamics (MD) method, with focus placed upon the influence of the electron relaxation effect. The validity of the numerical approach is checked against existing experimental results. While the electron relaxation effect is found negligible when the laser duration is much longer than the electron thermal relaxation time, it becomes significant if the laser duration matches the electron relaxation time, especially when the former is much shorter than the latter. The characteristics of thermo-mechanical interaction in the thin film are analyzed, and the influence of temperature-dependent material properties upon the thermoelastic response of the film quantified.
Redox reaction based negative differential resistance and bistability in nanoparticulate ZnO films
Authors: Ghosh Manoranjan , Gadkari S. C. , Gupta S. K.
Published: July 2012

Negative differential resistance (NDR) and bistability in the current-voltage (I-V) characteristics have been demonstrated for a simple device fabricated from ZnO nanoparticles (NPs). The Au/ZnO/Au device (ZnO nanoparticles size: 5–15 nm) attains ON and OFF states during forward and reverse voltage scans, respectively, akin to a cyclic voltammogram. The origin of the observed NDR and bistability is traced to the protonic conduction resulting from the dissociation of adsorbed moisture on the surface of ZnO nanoparticles. Water layers adsorbed on the ZnO surface dissociate into hydroxyl ions at the oxygen vacancy (Vo) site and transfer a proton to the nearby water molecule. Signature of NDR is created when the rate of redox reactions at the electrode is faster than the generation and transport of reactants. Oxygen vacancies considered as active sites for water dissociation reside predominantly at the surface due to their low formation energy. So, the degree of bistability and NDR are found to decrease with increasing particle size having relatively lower surface to volume ratio and eventually disappears for fairly large nanorods (dia. ∼100–200 nm and length 1–2 μm).
Magnetic island evolution in hot ion plasmas
Authors: Ishizawa A. , Waelbroeck F. L. , Fitzpatrick R. , Horton W. , Nakajima N.
Published: July 2012

Effects of finite ion temperature on magnetic island evolution are studied by means of numerical simulations of a reduced set of two-fluid equations which include ion as well as electron diamagnetism in slab geometry. The polarization current is found to be almost an order of magnitude larger in hot than in cold ion plasmas, due to the strong shear of ion velocity around the separatrix of the magnetic islands. As a function of the island width, the propagation speed decreases from the electron drift velocity (for islands thinner than the Larmor radius) to values close to the guiding-center velocity (for islands of order 10 times the Larmor radius). In the latter regime, the polarization current is destabilizing (i.e., it drives magnetic island growth). This is in contrast to cold ion plasmas, where the polarization current is generally found to have a healing effect on freely propagating magnetic island.
Electric field-induced scatterings in rough quantum wells of AlGaN/GaN high-mobility electronic transistors
Authors: Ji Dong , Lu Yanwu , Liu Bing , Jin Guangri , Liu Guipeng , Zhu Qinsheng , Wang Zhanguo
Published: July 2012

The electric field-induced surface and interface roughness scatterings have been investigated by taking both the forward and converse piezoelectric effects into account in AlGaN/GaN high electron mobility transistors. The results show that the converse piezoelectric effect can compensate the polarization fields in the barrier of AlGaN/GaN heterostructure, leading to weaker electric field scatterings. Additionally, the electronic mobilities limited by both surface and interface roughness can be modulated by the gate bias, based on which we can design the devices to obtain higher mobility.
Theoretical optimization of multi-layer InAs/GaAs quantum dots subject to post-growth thermal annealing for tailoring the photoluminescence emission beyond 1.3 μm
Authors: Ghosh K. , Naresh Y. , Srichakradhar Reddy N.
Published: July 2012

In this paper, we present theoretical analysis and computation for tuning the ground state (GS) photoluminescence (PL) emission of InAs/GaAs quantum dots (QDs) at telecommunication window of 1.3–1.55 μm by optimizing its height and base dimensions through quantum mechanical concepts. For this purpose, numerical modelling is carried out to calculate the quantized energy states of finite dimensional QDs so as to obtain the GS PL emission at or beyond 1.3 μm. Here, we also explored strain field altering the QD size distribution in multilayer heterostructure along with the changes in the PL spectra, simulation on post growth thermal annealing process which blueshifts the operating wavelength away from the vicinity of 1.3 μm and improvement of optical properties by varying the thickness of GaAs spacing. The results are discussed in detail which will serve as an important information tool for device scientist fabricating high quality semiconductor quantum structures with reduced defects at telecommunication wavelengths.
Efficient single particle detection with a superconducting nanowire
Authors: Azzouz Hatim , Dorenbos Sander N. , De Vries Daniel , Ureña Esteban Bermúdez , Zwiller Valery
Published: July 2012

Detection of α- and β-particles is of paramount importance in a wide range of applications. Current particle detectors are all macroscopic and have limited time resolution. We demonstrate a nanoscale particle detector with a small detection volume, high detection efficiency, short dead times and low dark count levels. We measure α- and β-particle detection efficiencies close to unity using different sources and also demonstrate blindness towards γ-rays. Our nanoscale detector offers particle detection measurements with unprecendented spatial resolution.
Regional Inequality and Decentralization: An Empirical Analysis
Authors: Lessmann Christian
Published: July 2012

This paper analyzes the impact of political and fiscal decentralization on regional inequalities, using a unique dataset which covers fifty-four countries at different stages of economic development. Cross-section and panel data estimations show that decentralization decreases regional inequalities in general. However, estimations using an interaction-variable approach imply that the effect depends on the level of economic development. While rich countries benefit from decentralization in that they achieve a more equal regional income distribution, decentralization may lead to higher regional inequalities in developing and emerging economies. The results point in the same direction for measures of fiscal and political decentralization, implying that autonomy in both decision making and fiscal authority are decisive in this context. Thus, when fostering decentralization in developing countries as proposed by international development agencies, the potential negative redistributional consequences should be taken into account.
Income Inequality, Decentralisation, and Regional Development in Western Europe
Authors: Tselios Vassilis , Rodríguez-Pose Andrés , Pike Andy , Tomaney John , Torrisi Gianpiero
Published: July 2012

This paper deals with the relationship between decentralisation, regional economic development, and income inequality within regions. Using multiplicative interaction models and regionally aggregated microeconomic data for more than 100 000 individuals in the European Union (EU), it addresses two main questions. First, whether fiscal and political decentralisation in Western Europe has an effect on within-regional interpersonal inequality. Second, whether this potential relationship is mediated by the level of economic development of the region. The results of the analysis show that greater fiscal decentralisation is associated with lower interpersonal income inequality, but, as regional income rises, further decentralisation is connected to a lower decrease in inequality. This finding is robust to the measurement and definition of income inequality, as well as to the weighting of the spatial units by their population size.
Placing Neoliberalism: The Rise and Fall of Ireland's Celtic Tiger
Authors: Kitchin Rob , O'Callaghan Cian , Boyle Mark , Gleeson Justin , Keaveney Karen
Published: July 2012

In this paper we provide an account of the property-led boom and bust which has brought Ireland to the point of bankruptcy. Our account details the pivotal role which neoliberal policy played in guiding the course of the country's recent history, but also heightens awareness of the how the Irish case might, in turn, instruct and illuminate mappings and explanations of neoliberalism's concrete histories and geographies. To this end, we begin by scrutinising the terms and conditions under which the Irish state might usefully be regarded as neoliberal. Attention is then given to uncovering the causes of the Irish property bubble, the housing oversupply it created, and the proposed solution to this oversupply. In the conclusion we draw attention to the contributions which our case study might make to the wider literature of critical human geographies of neoliberalism, forwarding three concepts which emerge from the Irish story which may have wider resonance, and might constitute a useful fleshing out of theoretical framings of concrete and particular neoliberalisms: path amplification, neoliberalism's topologies and topographies, and accumulation by repossession.
Geographies of Abstraction, Urban Entrepreneurialism, and the Production of New Cultural Spaces: The West Kowloon Cultural District, Hong Kong
Authors: Raco Mike , Gilliam Katherine
Published: July 2012

During the 1990s and 2000s understandings of urban politics have become dominated by narratives of neoliberal urban entrepreneurialism. Considerations of, and even interest in, the diversities that exist in the specific politics that shape place developments have often been relegated to a matter of secondary interest when understood in relation to broader structural global forces. This is particularly significant as urban development projects have become increasingly bound-up with cultural programmes, many of which are embedded in the social relations of places, yet are often dismissed as subservient to global, fast-track development logics. This paper draws on a study of the politics surrounding the development of one of Asia's largest culture-led urban development projects, the West Kowloon Cultural District, Hong Kong. It explores the complex relationships between contemporary development discourses and historically embedded postcolonial subjectivities and policy legacies. It uses the evidence to argue for more nuanced interpretations of change, and calls for a stronger focus on the concrete relations in and through which policy abstractions are formed.
The Significance and Implications of Being a Subprime Homeowner in the UK
Authors: Keasey Kevin , Veronesi Gianluca
Published: July 2012

The purpose of this paper is to provide a deeper understanding of the significance and implications of being a subprime homeowner in the UK. The results indicate that subprime individuals represent a mixture of socioeconomic groups, predominantly included in the light adverse and near prime categories of subprime lending, for whom credit adversity is generally a temporary phenomenon, which is likely to represent a transitory event in their lives. These borrowers have been at the heart of the UK subprime mortgage market, actively targeted not only by specialist lenders but also, more crucially, by mainstream players. Whereas for some individuals this market has provided an opportunity to experience the emotional and financial aspects of homeownership positively; for others becoming a subprime mortgage holder has increased the difficulties in their lives, affected their financial capability, and worsened their standards of living. Thus, the impact of the risk—reward mechanisms of subprime products has proved to be a difficult reality for certain socioeconomic groups. Furthermore, given the progressive deterioration in the transparency of the financial services industry, a significant proportion of subprime individuals has, unsurprisingly, struggled to appreciate the reasons why they faced problems in obtaining credit or a mortgage.
Transnational Regionalization and the Rescaling of the Chinese State
Authors: Su Xiaobo
Published: July 2012

Transnational regionalization has become a popular development policy among East Asian countries since the 1997 Asian financial crisis. Expanding upon Brenner's theory of state rescaling, this paper focuses on China's transnational regionalization projects and how the Chinese state rescales to implement these projects. Specifically, this paper has two objectives. First, by comparing two projects of transnational regionalization in which Yunnan participates—the Greater Mekong Subregion program and the Bangladesh—China—India—Myanmar forum—the paper critically probes the actual mechanisms (upward collaboration, downward implementation, and outward corporatism) deployed by the Chinese state to facilitate cross-border initiatives. This emphasis on the actual mechanisms thus theorizes back to Brenner's work, showing that regulatory restructuring entails complex power relations of competition and collaboration among various forces. Second, this paper examines how the Chinese state handles the territorial geopolitical relations which have emerged during the process of transnational regionalization. I seek to broaden the theoretical framework of state rescaling beyond the narrow confines of domestic city-regions to international political economy.
Mining Sacred Space: Law's Enactment of Competing Ontologies in the American West
Authors: Benson Melinda Harm
Published: July 2012

Current controversies regarding uranium mining in the American West are about more than competing legal requirements; they are about competing conceptualizations of space that are grounded in different ontologies. Laws—in this case the General Mining Law of 1872 and the National Historic Preservation Act of 1966—play a performative role by enacting and materializing these ontologies. The occupation of New Mexico's Mt. Taylor both by ‘old’ and by ‘new’ legal forms provides an opportunity to examine their corresponding spatiality. The National Historic Preservation Act, in particular, creates an interesting ‘new space’ that may have the capacity to challenge Eurocentric notions of ownership.
Paths of convergence for agriculture, health, and wealth
Authors: Dubé Laurette , Pingali Prabhu , Webb Patrick
Published: July 2012

This special feature calls for forward thinking around paths of convergence for agriculture, health, and wealth. Such convergence aims for a richer integration of smallholder farmers into national and global agricultural and food systems, health systems, value chains, and markets. The articles identify analytical innovation, where disciplines intersect, and cross-sectoral action where single, linear, and siloed approaches have traditionally dominated. The issues addressed are framed by three main themes: (
i
) lessons related to agricultural and food market growth since the 1960s; (
ii
) experiences related to the integration of smallholder agriculture into national and global business agendas; and (
iii
) insights into convergence-building institutional design and policy, including a review of complexity science methods that can inform such processes. In this introductory article, we first discuss the perspectives generated for more impactful policy and action when these three themes converge. We then push thematic boundaries to elaborate a roadmap for a broader, solution-oriented, and transdisciplinary approach to science, policies, and actions. As the global urban population crosses the 50% mark, both smallholder and nonsmallholder agriculture are keys in forging rural–urban links, where both farm and nonfarm activities contribute to sustainable nutrition security. The roadmaps would harness the power of business to reduce hunger and poverty for millions of families, contribute to a better alignment between human biology and modern lifestyles, and stem the spread of noncommunicable chronic diseases.
Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors
Authors: Islas Jose Francisco , Liu Yu , Weng Kuo-Chan , Robertson Matthew J. , Zhang Shuxing , Prejusa Allan , Harger John , Tikhomirova Dariya , Chopra Mani , Iyer Dinakar , Mercola Mark , Oshima Robert G. , Willerson James T. , Potaman Vladimir N. , Schwartz Robert J.
Published: July 2012

Unique insights for the reprograming of cell lineages have come from embryonic development in the ascidian
Ciona
, which is dependent upon the transcription factors
Ci
-ets1/2 and
Ci
-mesp to generate cardiac progenitors. We tested the idea that mammalian v-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and mesoderm posterior (MESP) homolog may be used to convert human dermal fibroblasts into cardiac progenitors. Here we show that murine ETS2 has a critical role in directing cardiac progenitors during cardiopoiesis in embryonic stem cells. We then use lentivirus-mediated forced expression of human ETS2 to convert normal human dermal fibroblasts into replicative cells expressing the cardiac mesoderm marker KDR
+
. However, although neither ETS2 nor the purported cardiac master regulator MESP1 can by themselves generate cardiac progenitors de novo from fibroblasts, forced coexpression of ETS2 and MESP1 or cell treatment with purified proteins reprograms fibroblasts into cardiac progenitors, as shown by the de novo appearance of core cardiac transcription factors, Ca
2+
transients, and sarcomeres. Our data indicate that ETS2 and MESP1 play important roles in a genetic network that governs cardiopoiesis.
Effective inhibition of cytomegalovirus infection by external guide sequences in mice
Authors: Jiang Xiaohong , Gong Hao , Chen Yuan-Chuan , Vu Gia-Phong , Trang Phong , Zhang Chen-Yu , Lu Sangwei , Liu Fenyong
Published: July 2012

Ribonuclease P complexed with external guide sequence (EGS) bound to mRNA represents a unique nucleic acid-based gene interference approach for modulation of gene expression. Compared with other strategies, such as RNA interference, the EGS-based technology is unique because a custom-designed EGS molecule can hybridize with any mRNA and recruit intracellular ribonuclease P for specific degradation of the target mRNA. It has not been reported whether the EGS-based technology can modulate gene expression in mice. In this study, a functional EGS was constructed to target the mRNA encoding the protease (mPR) of murine cytomegalovirus (MCMV), which is essential for viral replication. Furthermore, a unique attenuated strain of
Salmonella
was generated for gene delivery of EGS in cultured cells and in mice. Efficient expression of EGS was observed in cultured cells treated with the generated
Salmonella
vector carrying constructs with the EGS expression cassette. Moreover, a significant reduction in mPR expression and viral growth was found in MCMV-infected cells treated with
Salmonella
carrying the construct with the functional EGS sequence. When MCMV-infected mice were orally treated with
Salmonella
carrying EGS expression cassettes, viral gene expression and growth in various organs of these animals were reduced and animal survival improved. Our study suggests that EGS RNAs, when expressed following
Salmonella
-mediated gene transfer, effectively inhibit viral gene expression and infection in mice. Furthermore, these results demonstrate the feasibility of developing
Salmonella
-mediated delivery of EGS as a unique approach for treatment that reduces viral diseases in vivo.
Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape
Authors: Ferreon Allan Chris M. , Moosa Mahdi Muhammad , Gambin Yann , Deniz Ashok A.
Published: July 2012

Protein structure and function depend on a close interplay between intrinsic folding energy landscapes and the chemistry of the protein environment. Osmolytes are small-molecule compounds that can act as chemical chaperones by altering the environment in a cellular context. Despite their importance, detailed studies on the role of these chemical chaperones in modulating structure and dimensions of intrinsically disordered proteins have been limited. Here, we used single-molecule Förster resonance energy transfer to test the counteraction hypothesis of counterbalancing effects between the protecting osmolyte trimethylamine-N-oxide (TMAO) and denaturing osmolyte urea for the case of α-synuclein, a Parkinson’s disease-linked protein whose monomer exhibits significant disorder. The single-molecule experiments, which avoid complications from protein aggregation, do not exhibit clear solvent-induced cooperative protein transitions for these osmolytes, unlike results from previous studies on globular proteins. Our data demonstrate the ability of TMAO and urea to shift α-synuclein structures towards either more compact or expanded average dimensions. Strikingly, the experiments directly reveal that a 2∶1 [urea]∶[TMAO] ratio has a net neutral effect on the protein’s dimensions, a result that holds regardless of the absolute osmolyte concentrations. Our findings shed light on a surprisingly simple aspect of the interplay between urea and TMAO on α-synuclein in the context of intrinsically disordered proteins, with potential implications for the biological roles of such chemical chaperones. The results also highlight the strengths of single-molecule experiments in directly probing the chemical physics of protein structure and disorder in more chemically complex environments.
Community-wide convergent evolution in insect adaptation to toxic cardenolides by substitutions in the Na,K-ATPase
Authors: Dobler Susanne , Dalla Safaa , Wagschal Vera , Agrawal Anurag A.
Published: July 2012

The extent of convergent molecular evolution is largely unknown, yet is critical to understanding the genetics of adaptation. Target site insensitivity to cardenolides is a prime candidate for studying molecular convergence because herbivores in six orders of insects have specialized on these plant poisons, which gain their toxicity by blocking an essential transmembrane carrier, the sodium pump (Na,K-ATPase). We investigated gene sequences of the Na,K-ATPase α-subunit in 18 insects feeding on cardenolide-containing plants (spanning 15 genera and four orders) to screen for amino acid substitutions that might lower sensitivity to cardenolides. The replacement N122H that was previously shown to confer resistance in the monarch butterfly (Danaus plexippus) andChrysochusleaf beetles was found in four additional species,Oncopeltus fasciatusandLygaeus kalmii(Heteroptera, Lygaeidae),Labidomera clivicollis(Coleoptera, Chrysomelidae), andLiriomyza asclepiadis(Diptera, Agromyzidae). Thus, across 300 Myr of insect divergence, specialization on cardenolide-containing plants resulted in molecular convergence for an adaptation likely involved in coevolution. Our screen revealed a number of other substitutions connected to cardenolide binding in mammals. We confirmed that some of the particular substitutions provide resistance to cardenolides by introducing five distinct constructs of theDrosophila melanogastergene into susceptible eucaryotic cells under an ouabain selection regime. These functional assays demonstrate that combined substitutions of Q111and N122are synergistic, with greater than twofold higher resistance than either substitution alone and >12-fold resistance over the wild type. Thus, even across deep phylogenetic branches, evolutionary degrees of freedom seem to be limited by physiological constraints, such that the same molecular substitutions confer adaptation.
Volcanic ash layers illuminate the resilience of Neanderthals and early modern humans to natural hazards
Authors: Lowe John , Barton Nick , Blockley Simon , Ramsey Christopher Bronk , Cullen Victoria L. , Davies William , Gamble Clive , Grant Katharine , Hardiman Mark , Housley Rupert , Lane Christine S. , Lee Sharen , Lewis Mark , MacLeod Alison , Menzies Martin , Müller Wolfgang , Pollard Mark , Price Catherine , Roberts Andrew P. , Rohling Eelco J. , Satow Chris , Smith Victoria C. , Stringer Chris B. , Tomlinson Emma L. , White Dustin , Albert Paul , Arienzo Ilenia , Barker Graeme , Borić Dušan , Carandente Antonio , Civetta Lucia , Ferrier Catherine , Guadelli Jean-Luc , Karkanas Panagiotis , Koumouzelis Margarita , Müller Ulrich C. , Orsi Giovanni , Pross Jörg , Rosi Mauro , Shalamanov-Korobar Ljiljiana , Sirakov Nikolay , Tzedakis Polychronis C.
Published: July 2012

Marked changes in human dispersal and development during the Middle to Upper Paleolithic transition have been attributed to massive volcanic eruption and/or severe climatic deterioration. We test this concept using records of volcanic ash layers of the Campanian Ignimbrite eruption dated to
ca.
40,000 y ago (40 ka B.P.). The distribution of the Campanian Ignimbrite has been enhanced by the discovery of cryptotephra deposits (volcanic ash layers that are not visible to the naked eye) in archaeological cave sequences. They enable us to synchronize archaeological and paleoclimatic records through the period of transition from Neanderthal to the earliest anatomically modern human populations in Europe. Our results confirm that the combined effects of a major volcanic eruption and severe climatic cooling failed to have lasting impacts on Neanderthals or early modern humans in Europe. We infer that modern humans proved a greater competitive threat to indigenous populations than natural disasters.
Enzymatic resistance to the lipopeptide surfactin as identified through imaging mass spectrometry of bacterial competition
Authors: Hoefler B. Christopher , Gorzelnik Karl V. , Yang Jane Y. , Hendricks Nathan , Dorrestein Pieter C. , Straight Paul D.
Published: July 2012

Many species of bacteria secrete natural products that inhibit the growth or development of competing species. In turn, competitors may develop or acquire resistance to antagonistic molecules. Few studies have investigated the interplay of these countervailing forces in direct competition between two species. We have used an imaging mass spectrometry (IMS) approach to track metabolites exchanged between
Bacillus subtilis
and
Streptomyces
sp. Mg1 cultured together. Surfactin is a cyclic lipopeptide produced by
B. subtilis
that inhibits the formation of aerial hyphae by streptomycetes. IMS analysis exposed an addition of 18 mass units to surfactin in the agar proximal to
Streptomyces
sp. Mg1 but not other streptomycetes tested. The spatially resolved change in the mass of surfactin indicated hydrolysis of the molecule. We observed that the aerial growth of
Streptomyces
sp. Mg1 was resistant to inhibition by surfactin, which suggests that hydrolysis was a mechanism of resistance. To identify possible enzymes from
Streptomyces
sp. Mg1 with surfactin hydrolase activity, we isolated secreted proteins and identified candidates by mass spectrometry. We purified one candidate enzyme that hydrolyzed surfactin in vitro. We tested the role of this enzyme in surfactin resistance by deleting the corresponding gene from the
S
. Mg1 genome. We observed that aerial growth by the Δ
sfhA
mutant strain was now sensitive to surfactin. Our results identify an enzyme that hydrolyzes surfactin and confers resistance to aerial growth inhibition, which demonstrates the effective use of an IMS approach to track natural product modifications during interspecies competition.
Multiple B-vitamin depletion in large areas of the coastal ocean
Authors: Sañudo-Wilhelmy Sergio A. , Cutter Lynda S. , Durazo Reginaldo , Smail Emily A. , Gómez-Consarnau Laura , Webb Eric A. , Prokopenko Maria G. , Berelson William M. , Karl David M.
Published: July 2012

B vitamins are some of the most commonly required biochemical cofactors in living systems. Therefore, cellular metabolism of marine vitamin-requiring (auxotrophic) phytoplankton and bacteria would likely be significantly compromised if B vitamins (thiamin B1, riboflavin B2, pyridoxine B6, biotin B7, and cobalamin B12) were unavailable. However, the factors controlling the synthesis, ambient concentrations, and uptake of these key organic compounds in the marine environment are still not well understood. Here, we report vertical distributions of five B vitamins (and the amino acid methionine) measured simultaneously along a latitudinal gradient through the contrasting oceanographic regimes of the southern California-Baja California coast in the Northeast Pacific margin. Although vitamin concentrations ranged from below the detection limits of our technique to 30 pM for B2and B12and to ∼500 pM for B1, B6, and B7, each vitamin showed a different geographical and depth distribution. Vitamin concentrations were independent of each other and of inorganic nutrient levels, enriched primarily in the upper mesopelagic zone (depth of 100–300 m), and associated with water mass origin. Moreover, vitamin levels were below our detection limits (ranging from ≤0.18 pM for B12to ≤0.81 pM for B1) in extensive areas (100s of kilometers) of the coastal ocean, and thus may exert important constraints on the taxonomic composition of phytoplankton communities, and potentially also on rates of primary production and carbon sequestration.
Astrocyte dysfunction triggers neurodegeneration in a lysosomal storage disorder
Authors: Di Malta Chiara , Fryer John D. , Settembre Carmine , Ballabio Andrea
Published: July 2012

The role of astrocytes in neurodegenerative processes is increasingly appreciated. Here we investigated the contribution of astrocytes to neurodegeneration in multiple sulfatase deficiency (MSD), a severe lysosomal storage disorder caused by mutations in the
sulfatase modifying factor 1
(
SUMF1
) gene. Using Cre/Lox mouse models, we found that astrocyte-specific deletion of
Sumf1
in vivo induced severe lysosomal storage and autophagy dysfunction with consequential cytoplasmic accumulation of autophagic substrates. Lysosomal storage in astrocytes was sufficient to induce degeneration of cortical neurons in vivo. Furthermore, in an ex vivo coculture assay, we observed that
Sumf1
−/−
astrocytes failed to support the survival and function of wild-type cortical neurons, suggesting a non-cell autonomous mechanism for neurodegeneration. Compared with the astrocyte-specific deletion of
Sumf1
, the concomitant removal of
Sumf1
in both neurons and glia in vivo induced a widespread neuronal loss and robust neuroinflammation. Finally, behavioral analysis of mice with astrocyte-specific deletion of
Sumf1
compared with mice with
Sumf1
deletion in both astrocytes and neurons allowed us to link a subset of neurological manifestations of MSD to astrocyte dysfunction. This study indicates that astrocytes are integral components of the neuropathology in MSD and that modulation of astrocyte function may impact disease course.