bluuebunny/crossref_metadata_2025 huggingface dataset:
Was Archean Dharwar Craton Ever Stable? A Seismic Perspective
Authors: Pandey O. P. , Vedanti Nimisha , Srivastava R. P. , Uma V.
Published: June 2013

Indian shield comprising a number of Archean-Proterozoic cratons, forms one of the most dynamic, sheared and deformed continental segment amongst all stable areas of the earth. However, for a long time it has been believed that its lithosphere remained unaffected by episodic tectono-thermal and volcanic perturbations. Using available seismic data, an attempt has been made to study the seismic structure of the south Indian shield in order to examine the effects of such mantle processes on its overall crust-mantle structure. Our study suggests that by and large, Indian crust is intermediate to mafic in composition. On an average, only a couple of kilometers of the initially formed upper (granitic-gneissic) crust now remains in place and a thick chunk of the original lower crust has been consumed by the underlying thermally buoyant mantle due to sub-crustal erosion and then subsequently replaced by possibly as much as about 16 km thick magma layer on either side of the Moho. This study throws a new light on the geologic and geodynamic evolution of this region and contradicts the hitherto believed paleo-stability of the Indian shield.
Ground Penetrating Radar for Groundwater Exploration in Granitic Terrains: A Case Study from Hyderabad
Authors: Maheswari K. , Kumar P. Senthil , Mysaiah D. , Ratnamala K. , Rao M. Sri Hari , Seshunarayana T.
Published: June 2013

The Ground Penetrating Radar (GPR) is a newly developing geophysical tool for imaging the sub-surface and is potentially useful in groundwater exploration. We test its usefulness in characterizing a groundwater rich lineament near Gajularamaram in the Hyderabad granite terrain, where groundwater is limited to soil, weathering zone and lineaments. The lineament is 2 km long and 50-100 m wide, and oriented in WNW-ESE direction. It is characterized by many closely spaced sub-vertical fractures and faults, majority of which are parallel to the lineament. On either sides of the lineament, sub-horizontal sheet joints are abundant. The lineament is saturated with groundwater that discharge as springs at some places. About 450 m long, 400-100 MHz GPR data (∼5-30 m depth) were acquired along five profiles across the lineament. In the lineament, soil thickness varies from ∼0.5 m to 5 m, and is underlain by weathered granite. In the WNW part, a thick weathering zone (∼15 m) is present and a 10 m wide vertical anomaly zone (lineament) is also present. The presence of shallow reflectors at 1 m depth in the lineament is attributed to the groundwater surface. The GPR images reveal many sub horizontal to gently dipping reflectors, which are interpreted to be the sheet joints. The GPR data clearly reveal the saturated lineament, from which groundwater may migrate laterally to long distance through the sheet joints. We demonstrate the GPR as a rapid geophysical tool that can be used successfully to explore the near-surface groundwater.
Origin and Emplacement of the Higher Himalayan Leucogranite in the Eastern Himalaya: Constraints from Geochemistry and Mineral Chemistry
Authors: Singh R. K. Bikramaditya
Published: June 2013

The Higher Himalayan Leucogranites (HHLG) intruded into the high grade rocks of the Higher Himalayan Crystallines (HHC) in western Arunachal Pradesh, eastern Himalaya, yield distinctive field data, petrography, geochemical and mineral chemistry data. The HHLG mostly occur as sill like bodies of limited thickness and lateral extent within the HHC. The Arunachal HHLG are characterized by the presence of two micas; normative corundum; high contents of SiO2 (67 - 78 wt.%), Al2O3 (13 - 18 wt.%), A/CNK (0.98 - 1.44) and Rb (154 - 412 ppm); low contents of CaO (0.33 - 1.91 wt.%) and Sr (19 - 171 ppm), and a high ratio of FeO(tot)/MgO in biotite (2.54 - 4.82). These distinctive features, along with their strong depletion in high field strength elements (HFSE), suggest their affinity to peraluminous S-type granite generated by the partial melting of crustal material. Since the HHLG associated with high grade rocks of HHC and lack of basaltic magmatism, strongly suggests that the high grade rocks of HHC might represent the melt source and HHLG are product of pure crustal melt without any contamination of mantle material. Geothermobarometric estimations and mineral assemblages of the HHC metapelites confirm that the HHLG were probably generated in the middle crust (∼20 km) and the produced melts intruded the HHC in the form of sills/dykes.
The Mw 8.6 Indian Ocean Earthquake on 11 April 2012: Coseismic Displacement, Coulomb Stress Change and Aftershocks Pattern
Authors: Shrivastava Mahesh N. , Reddy C. D.
Published: June 2013

The Mw 8.6 Indian Ocean earthquake occurred on April 11, 2012 near the NW junction of three plates viz. Indian, Australian and Sunda plate, which caused widespread coseismic displacements and Coulomb stress changes. We analyzed the GPS data from three IGS sites PBRI, NTUS & COCO and computed the coseismic horizontal displacements. In order to have in-depth understanding of the physics of earthquake processes and probabilistic hazard, we estimated the coseismic displacements and associated Coulomb stress changes from two rectangular parallel fault geometries, constrained by Global Positioning System (GPS) derived coseismic displacements. The Coulomb stress changes following the earthquake found to be in the range of 5 to -4 bar with maximum displacement of ∼11 m near the epicenter. We find that most of the aftershocks occurred in the areas of increased Coulomb stress and concentrated in three clusters. The temporal variation of the aftershocks, not conformed to modified Omori’s law, speculating poroelastic processes. It is also ascertained that the spatio-temporal transient stress changes may promote the occurrence of the subsequent earthquakes and enhance the seismic risk in the region.
Effect of Geology and Geomorphology on Landuse/Landcover in Himalayan Foothill, Dehradun
Authors: Ansari Ziaur Rehman , Rao L. A. K. , Saran Sameer
Published: June 2013

A detailed geological, geomorphological and landuse/landcover study has been carried in a small watershed of Himalaya by visual interpretation of FCC prepared from band 123 of ASTER satellite imagery. On the basis of interpretation and field check, major litounits identified in the study area include Lesser Himalaya conglomerate consisting of quartzite, granite, phyllite boulder and pebble, Middle Siwalik sandstone and Upper Siwalik boulder beds and valley fill with Doon gravel of Holocene age. Geomorphologically the study area is characterized by typical Himalayan topography with rugged terrain. Various landforms identified and recognized include, Doon Fan Gravel Terrace, Doon Fan Gravel Dissected hill, Sub Recent Fan Terrace, Moderately Dissected Structural Hill, Piedmont Dissected Slope, River Terrace, Channel Bar and River channel. Supervised classification of ASTER False Colour Composite (FCC) (123) shows that the major landuse category in the study area is agriculture while major landcover class is forest covered land. The study shows the effect of geology and geomorphology on the type of landuse and landcover in an active tectonic zone of the study area.
The Effects of R-Rated Movies on Adolescent and Young Adult Religiosity: Media as Self-Socialization
Authors: Davignon Phil
Published: June 2013

Arnett (J Youth Adolesc 24:519–533, 1995 ) has suggested that media are a form of self-socialization, meaning that people choose the media they consume and in turn become socialized into certain beliefs and values. Research has suggested that viewing R-rated movies may lead to decreases in religiosity (Barry et al. in J Adult Deviance 19:66–78, 2012 ), but the direction of causality in this study is questionable. This research improves upon Barry, Padilla-Walker, and Nelson's study by including control variables for peer and family influence while utilizing panel data for longitudinal data analysis. Findings from the 2003, 2005, and 2007–2008 waves of the National Study of Youth and Religion (NSYR) suggest that viewing R-rated movies does indeed lead to decreases in church attendance and salience of religious faith, but it does not influence certainty and selective acceptance of religious beliefs. These results are discussed in light of self-socialization and their implications for how future studies might examine the relationship between R-rated movies and religiosity.
Effect of substrate competition in kinetic models of metabolic networks
Authors: Schäuble Sascha , Stavrum Anne Kristin , Puntervoll Pål , Schuster Stefan , Heiland Ines
Published: June 2013

Substrate competition can be found in many types of biological processes, ranging from gene expression to signal transduction and metabolic pathways. Although several experimental and in silico studies have shown the impact of substrate competition on these processes, it is still often neglected, especially in modelling approaches. Using toy models that exemplify different metabolic pathway scenarios, we show that substrate competition can influence the dynamics and the steady state concentrations of a metabolic pathway. We have additionally derived rate laws for substrate competition in reversible reactions and summarise existing rate laws for substrate competition in irreversible reactions.
Stabilization of absolute instability in spanwise wavy two-dimensional wakes
Authors: Hwang Yongyun , Kim Jinsung , Choi Haecheon
Published: June 2013

Controlling vortex shedding using spanwise-varying passive or active actuation (namely three-dimensional control) has recently been reported as a very efficient method for regulating two-dimensional bluff-body wakes. However, the mechanism of how the designed controller regulates vortex shedding is not clearly understood. To understand this mechanism, we perform a linear stability analysis of two-dimensional wakes, the base flow of which is modified with a given spanwise waviness. Absolute and convective instabilities of the spanwise wavy base flows are investigated using Floquet theory. Two types of base-flow modification are considered: varicose and sinuous. Both of these modifications attenuate absolute instability of two-dimensional wakes. In particular, the varicose modification is found to be much more effective in the attenuation than the sinuous one, and its spanwise lengths resulting in maximum attenuation show good agreement with those in three-dimensional controls. The physical mechanism of the stabilization is found to be associated with the formation of streamwise vortices from tilting of two-dimensional Kármán vortices and the subsequent tilting of these streamwise vortices by the spanwise shear in the base flow. Finally, the sensitivity of absolute instability to spanwise wavy base-flow modification is investigated. It is shown that absolute instability of two-dimensional wakes is much less sensitive to spanwise wavy base-flow modification than to two-dimensional modification. This suggests that the high efficiency observed in several three-dimensional controls is not due to the sensitive response of the wake instability to the spanwise waviness in the base flow.
The Second Formation of Islamic Law: The Post-Mongol Context of the Ottoman Adoption of a School of Law
Authors: Burak Guy
Published: June 2013

This article proposes a comparative analytical framework to study changes in Islamic law during the post-Mongol period, particularly the rise of the official school of law (or statemadhhab). Taking as my case study the Ottoman adoption of a particular branch within the Sunni Hanafi school of law, I suggest that this adoption marks a new chapter in Islamic legal history. In earlier periods, while rulers appointed judges and thus regulated the adjudication procedures, they did not intervene, at least theoretically, in the structure and doctrine of the schools of law, which remained the relatively autonomous realm of the jurists. The Ottoman adoption of the school, by contrast, was not merely an act of state patronage, since the dynasty played an important role in regulating the school's structure and doctrine. To this end, it employed a set of administrative and institutional practices, such as the development of an imperial learned hierarchy with standardized career and training tracks and the appointment of jurisconsults (muftis). Some of these practices were found in other polities across the eastern Islamic lands in the post-Mongol period, but these similarities have not been treated comparatively in modern historiography. They suggest that the Ottoman case was part of a broader legal culture that spanned several polities across the region. This article outlines a framework that will enable historians of Islamic law to treat these similarities in a more coherent manner. The framework raises key issues in the historiography of Islamic law and its nineteenth-century modernization.
A Mask of Calm: Emotion and Founding the Kingdom of Bunyoro in the Sixteenth Century
Authors: Schoenbrun David
Published: June 2013

Rich vernacular traditions about the aftermaths of the social trauma of a major famine, sometime in sixteenth-century eastern Africa, narrate the founding of a new dynasty in Bunyoro, one of the region's oldest monarchies. Scholars often understand such traditions about the founding of new dynasties as chartering the new political order. Whether traditions credit that order with the aura of antiquity or strengthen it by excluding social elements discordant with the new orchestrations of power, they are exercises in legitimation. When scholars recognize that such traditions were set in the aftermath of widespread violence, a spirit of mourning emerges in them. Spirits of mourning, joined to those of legitimation, shape traditions about the founding of a new dynasty by deftly inflecting the problem of accountability. In Bunyoro, traditions about its founder depict him as a barbarian cultural neophyte, of fluctuating emotional stability, improvising a new political order. These unflattering, realistic representations of the founding dynast's affective comportment were designed to appeal to emotional repertoires in the different life experiences of audience members, enlisting their participation in the project of reviving sovereignty in the aftermaths of traumatic violence. Mourning and legitimation run through historical narratives initiating an aftermath to structural violence, and reveal that loss and worry shape narratives of transformed sovereign authority, and revive it in the aftermaths of structural violence. Mourning lends emotional depth and counterpoint to matters of bureaucracy, economy, gender, and so forth, in crafting satisfying accounts of transformation and accountability in political life. That emotional depth, in turn, helps explain the durability of traditions.
The Politics of Presence: Voice, Deity Possession, and Dilemmas of Development Among Tibetans in the People's Republic of China
Authors: Makley Charlene E.
Published: June 2013

Taking inspiration from linguistic anthropological approaches to the work of the Russian philosopher and literary critic Mikhail Bakhtin (1895–1975), this article uses a Bakhtinian perspective on voice as contested presence to analyze the post-Mao revival of mountain deity possession practices among Tibetans in China's northwestern province of Qinghai. I respond to recent work that suggests that state-led development processes have intensified grassroots contests over the moral sources of authority and legitimacy in China, by contrasting the ambivalent voices of an urbanizing village's Tibetan Party secretary with those of the village's deity medium, during a mid-2000s village conflict. The conflict underscored a crisis of authority or moral “presence” among Tibetans under intensifying central state-led development pressures that for many carried forward the disenfranchisement of Tibetans that started in the 1950s.
Primitiveness, Metaontology, and Explanatory Power
Authors: BENOVSKY JIRI
Published: June 2013

Metaphysical theories heavily rely on the use of primitives to which they typically appeal. I will start by examining and evaluating some traditional well-known theories and I will discuss theroleof primitives in metaphysical theories in general. I will then turn to a discussion of claims of ‘equivalence’ between theories that, I think, depend on equivalences of primitives, and I will explore thenatureof primitives. I will then claim that almost all explanatory power of metaphysical theories comes from their primitives, and so I will turn to scrutinize the notion of ‘power’ and ‘explanatory’.
TEMPERATURE AND DROUGHT STRESS EFFECTS ON GROWTH AND DEVELOPMENT OF BAMBARA GROUNDNUT (VIGNA SUBTERRANEA L.)
Authors: AL SHAREEF IBRAHEEM , SPARKES DEBBIE , AZAM-ALI SAYED
Published: June 2013

The effect of drought and temperature on the growth and development of bambara groundnut (Vigna subterranea (L.) Verdc.) was studied in controlled environment glasshouses in the United Kingdom. There were two landraces, S19-3 (from a hot, dry environment; Namibia) and Uniswa Red (from a cool, wet environment; Swaziland), two temperature regimes (23 °C and 33 °C) and three watering regimes (2006; fully irrigated), 2007 (drought imposed at 77 days after sowing (DAS)) and 2008 (drought imposed at 30 DAS)). Bambara groundnut responded to drought by slowing the rate of leaf area expansion and reducing final canopy size and total dry matter (TDM). Drought also caused significant reductions in pod dry matter, pod numbers and harvest index (HI), leading to a decrease in final yield that was different between landraces. Throughout the three growing seasons, landraces grown at 33 °C produced more TDM than the landraces grown at 23 °C. The two landraces differed in their phenology; S19-3 exhibited a reduced phenology where leaf numbers started to decrease before Uniswa Red at both temperatures, while Uniswa Red maintained the longest life cycle. The lowest pod yield was produced by Uniswa Red in 2008 at 33 °C (maximum of 35.5 gm−2), while S19-3 produced a minimum pod yield of 56.6 gm−2 at 33 °C, also in 2008. However, both landraces produced considerably more pod yield at 23 °C throughout the three growing seasons (minimum of 151 gm−2 and 162 gm−2 for Uniswa Red and S19-3, respectively). Under moderate drought, S19-3 at 33 °C gave the highest pod yield (365 gm−2) among the treatments throughout the three growing seasons and maintained HI better under drought. Despite being from a hot, dry environment, S19-3 also performed well at low temperature, which indicates the adaptation of S19-3 to low temperature that it also experiences in the country of origin.
Neurocognitive functioning in bipolar depression: a component structure analysis
Authors: Gallagher P. , Gray J. M. , Watson S. , Young A. H. , Ferrier I. N.
Published: June 2013

Background

Previous studies of neurocognitive performance in bipolar disorder (BD) have focused predominantly on euthymia. In this study we aimed to compare the neurocognitive profile of BD patients when depressed with healthy controls and explore the component structure of neurocognitive processes in these populations.

Method

Cognitive tests of attention and executive function, immediate memory, verbal and visuospatial learning and memory and psychomotor speed were administered to 53 patients with a SCID-verified diagnosis of BD depression and 47 healthy controls. Test performance was assessed in terms of statistical significance, effect size and percentile standing. Principal component analysis (PCA) was used to explore underlying cognitive factor structure.

Results

Multivariate analysis revealed an overall group effect, depressed BD patients performing significantly worse than controls. Patients performed significantly worse on 18/26 measures examined, with large effect sizes (d > 0.8) on tests of speed of processing, verbal learning and specific executive/working memory processes. Almost all tests produced at least one outcome measure on which ∼25–50% of the BD sample performed at more than 1 standard deviation (s.d.) below the control mean. Between 20% and 34% of patients performed at or below the fifth percentile of the control group in working memory, verbal learning and memory, and psychomotor/processing speed. PCA highlighted overall differences between groups, with fewer extracted components and less specificity in patients.

Conclusions

Overall, neurocognitive test performance is significantly reduced in BD patients when depressed. The use of different methods of analysing cognitive performance is highlighted, along with the relationship between processes, indicating important directions for future research.
Wartime experiences and their implications for the everyday lives of older people
Authors: SIXSMITH JUDITH , SIXSMITH ANDREW , CALLENDER MATTHEW , CORR SUSAN
Published: June 2013

Past research has documented the influences that ‘traumatic’ memories of war have on older people's mental health (e.g.Post-Traumatic Stress Disorder). However, fewer studies have explored the longer-term implications of wartime experiences for older men and women's everyday lives. This article explores the impact of Second World War experiences on older men and women living in the United Kingdom (UK), to provide an insight into how such experiences influence how they construct their daily lives. Forty UK-based participants born between 1914 and 1923 were interviewed as part of the ENABLE-AGE project that was undertaken in five European countries. The key concepts underpinning the interview schedule were: home, independence, participation, health and wellbeing, and societal supports. The data were analysed using a grounded theory approach. Participants emphasised how wartime experiences continue to hold significance within their lives and settings some 60 years later. Seven themes emerged from the analysis. Four of these reflect the way wartime experiences remain important influences on participants' present-day social worlds: comradeship, storytelling about the war, community and alienation, and long-term physical effects. A further three themes reflect how skills and personal characteristics defined by wartime experiences are embedded in the way many older people continue to negotiate and structure their practical lives: managing, resilience and adaptability, and independence.
Isolation and genetic characterization of naturally NS-truncated H3N8 equine influenza virus in South Korea
Authors: NA W. , KANG B. , KIM H.-I. , HONG M. , PARK S.-J. , JEOUNG H.-Y. , AN D.-J. , MOON H. , KIM J.-K. , SONG D.
Published: June 2013

Equine influenza virus (EIV) causes a highly contagious respiratory disease in equids, with confirmed outbreaks in Europe, America, North Africa, and Asia. Although China, Mongolia, and Japan have reported equine influenza outbreaks, Korea has not. Since 2011, we have conducted a routine surveillance programme to detect EIV at domestic stud farms, and isolated H3N8 EIV from horses showing respiratory disease symptoms. Here, we characterized the genetic and biological properties of this novel Korean H3N8 EIV isolate. This H3N8 EIV isolate belongs to the Florida sublineage clade 1 of the American H3N8 EIV lineage, and surprisingly, possessed a non-structural protein (NS) gene segment, where 23 bases of the NS1-encoding region were naturally truncated. Our preliminary biological data indicated that this truncation did not affect virus replication; its effect on biological and immunological properties of the virus will require further study.
Effects of temperature on heat-shock responses and survival of two species of marine invertebrates from sub-Antarctic Marion Island
Authors: Clusella-Trullas S. , Boardman L. , Faulkner K.T. , Peck L.S. , Chown S.L.
Published: June 2013

This study examined high temperature survival and heat shock protein 70 (Hsp70) responses to temperature variation for two marine invertebrate species on sub-Antarctic Marion Island. The isopodExosphaeroma gigasLeach and the amphipodHyale hirtipalmaDana had the same tolerance to high temperature. The mean upper temperature which was lethal for 50% of the population (upper lethal temperature, ULT50) was 26.4°C for both species. However, the isopodE. gigasshowed significant plasticity of ULT50, with a positive response to acclimation. In addition, the isopod had a heat shock response of Hsp70 at all acclimations, and the amount of Hsp70 protein increased significantly from basal levels upon an acute warm exposure after a cold acclimation. By contrast, the amphipodH. hirtipalmashowed limited plasticity of ULT50and no evidence for a heat shock response (failure of three different Hsp70 antibodies to bind to the extracted 70kDa proteins). Overall, these results reflect different flexibility of thermal tolerance of intertidal invertebrate species on Marion Island, with possible variation in the underlying cellular mechanisms, suggesting that warming associated with climate change may result in changes in species assemblage structure in sub-polar environments.
Moving architecture and flattening politics: examining adaptability through a narrative of design
Authors: Schmidt Robert , Sage Daniel , Eguchi Toru , Dainty Andy
Published: June 2013

Our paper addresses how building design elucidates the connection between two definitions of politics: ‘Big Politics’ and micropolitics. We will seek to examine how these two versions of politics are imbricated; how, in other words, codified ideologies and political institutions circulate within the everyday practices by which new actors and sites of contestation enter the social collective. The conceptual space for this argument has already been mapped out by various authors, including Gilles Deleuze and Félix Guattari, Bruno Latour and Michel Foucault. These authors have variously proposed how powerful totalities always travel along small, fragile conduits. Or, as Deleuze and Guattari put it, ‘the boss's office is as much at the end of the hall as on top of the tower’.
Dynamical Electron Backscatter Diffraction Patterns. Part I: Pattern Simulations
Authors: Callahan Patrick G. , De Graef Marc
Published: June 2013

A new approach for the simulation of dynamic electron backscatter diffraction (EBSD) patterns is introduced. The computational approach merges deterministic dynamic electron-scattering computations based on Bloch waves with a stochastic Monte Carlo (MC) simulation of the energy, depth, and directional distributions of the backscattered electrons (BSEs). An efficient numerical scheme is introduced, based on a modified Lambert projection, for the computation of the scintillator electron count as a function of the position and orientation of the EBSD detector; the approach allows for the rapid computation of an individual EBSD pattern by bi-linear interpolation of a master EBSD pattern. The master pattern stores the BSE yield as a function of the electron exit direction and exit energy and is used along with weight factors extracted from the MC simulation to obtain energy-weighted simulated EBSD patterns. Example simulations for nickel yield realistic patterns and energy-dependent trends in pattern blurring versus filter window energies are in agreement with experimental energy-filtered EBSD observations reported in the literature.
Androgen and PARP-1 Regulation of TRPM2 Channels after Ischemic Injury
Authors: Shimizu Takeru , Macey Tara A , Quillinan Nidia , Klawitter Jelena , Perraud Anne-Laure L , Traystman Richard J , Herson Paco S
Published: June 2013

The calcium-permeable transient receptor potential M2 (TRPM2) ion channel was recently demonstrated to have a sexually dimorphic contribution to ischemic brain injury, with inhibition or knockdown of the channel protecting male brain preferentially. We tested the hypothesis that androgen signaling is required for this male-specific cell-death pathway. Additionally, we tested the hypothesis that differential activation of the enzyme poly (ADP-ribose) polymerase-1 (PARP-1) is responsible for male-specific TRPM2 channel activation and neuronal injury. We observed that administration of the TRPM2 inhibitor clotrimazole (CTZ) 2 hours after onset of ischemia reduced infarct volume in male mice and that protection from ischemic damage by CTZ was abolished by removal of testicular androgens (castration; CAST) and rescued by androgen replacement. Male PARP-1 knockout mice had reduced ischemic damage compared with WT mice and inhibition of TRPM2 with CTZ failed to reduce infarct size. Lastly, we observed that ischemia increased PARP activity in the peri-infarct region of male mice to a greater extent than female mice and the difference was abolished in CAST male mice. Data presented in the current study indicate that TRPM2-mediated neuronal death in the male brain requires intact androgen signaling and PARP-1 activity.
Chronic Rapamycin Restores Brain Vascular Integrity and Function Through NO Synthase Activation and Improves Memory in Symptomatic Mice Modeling Alzheimer’s Disease
Authors: Lin Ai-Ling , Zheng Wei , Halloran Jonathan J , Burbank Raquel R , Hussong Stacy A , Hart Matthew J , Javors Martin , Shih Yen-Yu Ian , Muir Eric , Fonseca Rene Solano , Strong Randy , Richardson Arlan G , Lechleiter James D , Fox Peter T , Galvan Veronica
Published: June 2013

Vascular pathology is a major feature of Alzheimer’s disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias.
The crystal structure of multidrug-resistance regulator RamR with multiple drugs
Authors: Yamasaki Suguru , Nikaido Eiji , Nakashima Ryosuke , Sakurai Keisuke , Fujiwara Daisuke , Fujii Ikuo , Nishino Kunihiko
Published: June 2013

RamR is a transcriptional repressor of the gene-encoding RamA protein, which controls the expression of the multidrug efflux system genes acrAB-tolC. RamR is an important multidrug-resistance factor, however, its structure and the identity of the molecules to which it responds have been unknown. Here, we report the crystal structure of RamR in complex with multiple drugs, including berberine, crystal violet, dequalinium, ethidium bromide and rhodamine 6G. All compounds are found to interact with Phe155 of RamR, and each compound is surrounded by different amino acid residues. Binding of these compounds to RamR reduces its DNA-binding affinity, which results in the increased expression of ramA. Our results reveal significant flexibility in the substrate-recognition region of RamR, which regulates the bacterial efflux participating in multidrug resistance.
The Embeddedness of Planning in Cultural Contexts: Theoretical Foundations for the Analysis of Dynamic Planning Cultures
Authors: Othengrafen Frank , Reimer Mario
Published: June 2013

This paper recognises the need to study the complex relations between spatial planning and cultural contexts in a more comprehensive way. The objective is to contribute to a theoretical basis and conceptual framework for a systematic analysis of spatial planning, that is, planning practices related to a cultural and social context, on the basis of a complex system of criteria. This may contribute to achieving a better understanding of the complex relationships between the cultural context—including the specific socioeconomic patterns and related cultural norms, values, traditions, and attitudes—and spatial planning as an operative instrument of territorial policy by introducing the term ‘planning culture’. Therefore, as culture is subtle and complex in nature and is based on fluid concepts, theoretical approaches of cultural change are also introduced to provide a more dynamic conception of planning cultures to analyse and understand recent changes in spatial planning.
Decentralisation and the Changing Geographies of Political Marginalisation in Kerala
Authors: Williams Glyn , Thampi Binitha V
Published: June 2013

One of the benefits often claimed for ‘moving’ the state closer to people through the institutional reforms of democratic decentralisation is an improvement in the inclusion of politically marginalised groups. Decentralisation promises to deliver both the closer physical presence of centres of government and the formalisation of practices of representation at the grassroots. These changes in turn are expected to provide opportunities for historically marginalised groups to improve their associational capacities, and to gain recognition as rights-bearing citizens. This idea is examined through the experience of Kerala, which has one of the most thorough programmes of democratic decentralisation within India. Decentralisation has indeed provided new pathways to engage with local government. However, attempts to ‘rescale’ the state to the local level have also reshaped existing institutional channels for representation, political discourses, and everyday state practices, in ways which produce new microgeographies of exclusion. This paper highlights the importance of these everyday experiences of marginalisation for programmes of state reform. It argues that if they are ignored, decentralisation risks reproducing narrow forms of majoritarian localism, and its potential to contribute to building substantive democracy will be lost.
Getting the Foundations Right: Spatial Building Blocks for Official Population Statistics
Authors: Cockings Samantha , Harfoot Andrew , Martin David , Hornby Duncan
Published: June 2013

When publishing official population statistics, many national statistical organisations define small areas termed ‘building blocks’ which are then aggregated into larger ‘output zones’ for data release. While output zones are known to have enormous influence on spatial analysis, there has not been any systematic analysis of the effect of building blocks on characteristics of output zones. This paper evaluates current international practice in building block design, identifying key conceptual and practical issues. Using the example of six local authorities in England and Wales, it employs automated zone design to evaluate the influence of two sets of building blocks (street blocks and postcodes) on output zone characteristics. Household-level census data, accessed under secure conditions, are used to evaluate the impact on both newly designed and maintained output zones. Postcodes are shown to be more effective building blocks than street blocks, providing more uniform population and household sizes, greater precision for matching postcoded data to census data, and enabling more zones to be maintained. However, street blocks deliver more compact output zones and greater internal homogeneity of tenure and accommodation type. The scale effect of the modifiable areal unit problem and the specific geographical patterning of variables are both shown to be important factors when designing building blocks. These findings have directly informed policies and processes for the 2011 Census in England and Wales and provide useful conceptual and practical guidance for any national statistical organisation or analyst designing their own building blocks. The paper concludes that some aspects of international building block design practice could be more effectively harmonised but that such design should always be nationally specific to incorporate locally varying conceptual and practical issues. Further research should extend this analysis to other building block types, notably grid squares.
Territorial Cohesion, Territorialism, Territoriality, and Soft Planning: A Critical Review
Authors: Faludi Andreas
Published: June 2013

Territorial cohesion is a shared EU competence, but what is territory? This paper seeks to alert planners—in particular those involved in European spatial planning—that common-sense answers do not necessarily apply: it is not a container. A view of macrospace as filled with territories-as-containers—territorialism—is nonetheless the basis for common misunderstandings about the EU, and also about European planning, now being articulated in terms of territorial cohesion. Leaving the container view behind means that control over territories—territoriality—must be negotiated, something that relational regionalism also suggests. The planning literature is beginning to absorb such views, articulating soft rather than hard forms of planning for ‘soft spaces’. Hard planning is bound to continue, but it will be embedded in new practices, including the conceptualisation of multiple visions on territory.
Double Exposures and Decision Making: Adaptation Policy and Planning in Ireland's Coastal Cities during a Boom—Bust Cycle
Authors: Jeffers James M
Published: June 2013

The importance of the interactions between global environmental and socioeconomic changes in shaping vulnerability and exposure to hazards is now increasingly recognised. However, relatively little attention has been focused on the ways in which these interactions help to shape planning and policy in response to both processes. This paper examines how the intersections between the twin crises of economic recession and climate change are influencing hazards mitigation policy and climate change adaptation planning in three of Ireland's coastal cities. The cities of Dublin, Cork, and Galway are important case studies for this analysis due to the magnitude of socioeconomic and environmental changes they have witnessed in recent years. The paper begins by using the double-exposure framework to analyse how the interactions between global environmental and socioeconomic change have produced the contextual environment within which decision making and policy formation take place. This is followed by the presentation and analysis of the results of semistructured interviews with local decision makers and stakeholders. These illustrate that the interactions between environmental change and economic crisis have created the material and ideological conditions in which a neoliberal growth centred discourse of economic development dominates all areas of decision making and-policy. This has important implications for environmental policy and planning in cities, promoting a vision of a modern competitive city in which technological solutions are the preferred means of addressing flood risks. These decisions in turn reshape the exposures and vulnerabilities of local communities.
Ethnic and Religious Penalties in a Changing British Labour Market from 2002 to 2010: The Case of Unemployment
Authors: Khattab Nabil , Johnston Ron
Published: June 2013

Most analyses of ethnic penalties in the UK labour market focus on one source of minority-group disadvantage only: colour racism, based on people's self-identified ethnicity. Some authors have argued that operating alongside those penalties, and in general exacerbating them, are further disadvantages reflecting cultural racism: in the UK it is argued that particular religious groups suffer these additional penalties—especially Muslims. A number of studies have confirmed the presence of these two types of disadvantage, but almost all of them have used cross-sectional data only and so were unable to test directly whether the penalties are more severe at times of economic recession and growing cultural tensions—such as those experienced in the UK after 9/11 and 7/7. This paper provides clear evidence of both the anticipated dual penalties and their increase at the end of the decade, using a very large annual cross-sectional survey for the years 2002 to 2010.
Coalition Culls and Zoonotic Ontologies
Authors: Atkins Peter J , Robinson Philip A
Published: June 2013

Diseases which can pass between animals and humans (zoonoses) have been headline news several times in the last ten years. This paper looks at bovine tuberculosis (bTB) in the United Kingdom, which, although not a major health hazard for humans, has been problematic for farmers and the veterinary health institutions. At its current rate of spread, the disease will cost the authorities £1 billion in compensation to farmers for slaughtered animals and in administrative expenses over the next decade. The present Coalition government is planning to cull badgers in England because they are the principal wildlife reservoir of bTB and are said to pass infection to cattle. We argue in five stories that the heterogeneities of bTB help explain the difficulties in dealing with it. In our opinion, the present reductive set of policies would be improved by taking this ontological multiplicity into account.
Histone deacetylase 10 promotes autophagy-mediated cell survival
Authors: Oehme Ina , Linke Jan-Peter , Böck Barbara C. , Milde Till , Lodrini Marco , Hartenstein Bettina , Wiegand Inga , Eckert Christian , Roth Wilfried , Kool Marcel , Kaden Sylvia , Gröne Hermann-Josef , Schulte Johannes H. , Lindner Sven , Hamacher-Brady Anne , Brady Nathan R. , Deubzer Hedwig E. , Witt Olaf
Published: June 2013

Significance

Resistance to chemotherapy is one of the major challenges in oncology. Neuroblastoma is the most common extracranial solid tumor in childhood, and the successful response of high-risk patients to chemotherapy remains poor. Our work showed that the so far poorly studied histone deacetylase (HDAC)10 promotes autophagy-mediated cell survival and signals poor outcome in independent high-risk patient cohorts. Inhibition of HDAC10 sensitized tumor cells for cytotoxic drug treatment. These results offer HDAC10 as a potential biomarker for treatment response of high-risk tumors and open new avenues for developing selective treatment strategies to bypass drug resistance of these tumors.
Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis
Authors: Cabral Horacio , Murakami Mami , Hojo Hironori , Terada Yasuko , Kano Mitsunobu R. , Chung Ung-il , Nishiyama Nobuhiro , Kataoka Kazunori
Published: June 2013

Nanoscaled drug-loaded carriers are of particular interest for efficient tumor therapy as numerous studies have shown improved targeting and efficacy. Nevertheless, most of these studies have been performed against allograft and xenograft tumor models, which have altered microenvironment features affecting the accumulation and penetration of nanocarriers. Conversely, the evaluation of nanocarriers on genetically engineered mice, which can gradually develop clinically relevant tumors, permits the validation of their design under normal processes of immunity, angiogenesis, and inflammation. Therefore, considering the poor prognosis of pancreatic cancer, we used the elastase 1-promoted luciferase and Simian virus 40 T and t antigens transgenic mice, which develop spontaneous bioluminescent pancreatic carcinoma, and showed that long circulating micellar nanocarriers, incorporating the parent complex of oxaliplatin, inhibited the tumor growth as a result of their efficient accumulation and penetration in the tumors. The reduction of the photon flux from the endogenous tumor by the micelles correlated with the decrease of serum carbohydrate-associated antigen 19-9 marker. Micelles also reduced the incidence of metastasis and ascites, extending the survival of the transgenic mice.
Conformational dynamics control ubiquitin-deubiquitinase interactions and influence in vivo signaling
Authors: Phillips Aaron H. , Zhang Yingnan , Cunningham Christian N. , Zhou Lijuan , Forrest William F. , Liu Peter S. , Steffek Micah , Lee James , Tam Christine , Helgason Elizabeth , Murray Jeremy M. , Kirkpatrick Donald S. , Fairbrother Wayne J. , Corn Jacob E.
Published: June 2013

Ubiquitin is a highly conserved eukaryotic protein that interacts with a diverse set of partners to act as a cellular signaling hub. Ubiquitin’s conformational flexibility has been postulated to underlie its multifaceted recognition. Here we use computational and library-based means to interrogate core mutations that modulate the conformational dynamics of human ubiquitin. These ubiquitin variants exhibit increased affinity for the USP14 deubiquitinase, with concomitantly reduced affinity for other deubiquitinases. Strikingly, the kinetics of conformational motion are dramatically slowed in these variants without a detectable change in either the ground state fold or excited state population. These variants can be ligated into substrate-linked chains in vitro and in vivo but cannot solely support growth in eukaryotic cells. Proteomic analyses reveal nearly identical interaction profiles between WT ubiquitin and the variants but identify a small subset of altered interactions. Taken together, these results show that conformational dynamics are critical for ubiquitin–deubiquitinase interactions and imply that the fine tuning of motion has played a key role in the evolution of ubiquitin as a signaling hub.
Water diffusion in brain cortex closely tracks underlying neuronal activity
Authors: Tsurugizawa Tomokazu , Ciobanu Luisa , Le Bihan Denis
Published: June 2013

Neuronal activity results in a local increase in blood flow. This concept serves as the basis for functional MRI. Still, this approach remains indirect and may fail in situations interfering with the neurovascular coupling mechanisms (drugs, anesthesia). Here we establish that water molecular diffusion is directly modulated by underlying neuronal activity using a rat forepaw stimulation model under different conditions of neuronal stimulation and neurovascular coupling. Under nitroprusside infusion, a neurovascular-coupling inhibitor, the diffusion response and local field potentials were maintained, whereas the hemodynamic response was abolished. As diffusion MRI reflects interactions of water molecules with obstacles (e.g., cell membranes), the observed changes point to a dynamic modulation of the neural tissue structure upon activation, which remains to be investigated. These findings represent a significant shift in concept from the current electrochemical and neurovascular coupling principles used for brain imaging, and open unique avenues to investigate mechanisms underlying brain function.