bluuebunny/crossref_metadata_2025 huggingface dataset:
Social inequality and urban regeneration in Barcelona city centre: reconsidering success
Authors: Arbaci Sonia , Tapada-Berteli Teresa
Published: July 2012

Across some Southern European cities, urban renewal programmes are seen as the primary means of alleviating concentrations of poverty and social inequality by improving local living conditions. Over the long-term delivery phase, such area-based interventions are often confronted with unforeseen macro-scale urban dynamics related to mobility of people and capital. Since the mid-1980s, Barcelona’s municipality has introduced a series of urban renewal programmes – PERIs (Special Plans of Interior Reform) – to deal with deprived neighbourhoods of the city centre suffering from poor housing conditions, inadequate services and infrastructure, and decreasing population. Selective demolition (or esponjamiento) was a key mechanism to create new open spaces in the crowded city centre whilst building new housing stock to relocate families. Urban interventions ranged from large-scale demolition of entire blocks in the Raval neighbourhood to micro-scale demolitions in the Santa Caterina & Sant Pere neighbourhood. This paper seeks to evaluate and compare the social and urban effects of urban renewal programmes in the two neighbourhoods between 1985 and 2009. Longitudinal quantitative analysis is employed to isolate demographic, socio-economic and housing changes, consider the remarkable increase in foreign population unforeseen in the original programmes, and hint at changes in space consumption and housing affordability. Finally, questions on inequality and state-led gentrification are raised, whilst considering dynamics of social and spatial desegregation as well as population substitution and displacement.
Cross-border-cooperation in the Upper Adriatic: A new kind of citizenship?
Authors: Nadalutti Elisabetta
Published: July 2012

The 1990s witnessed a strong debate around the emergence of a new kind of citizenship in Europe. This article analyses the ways in which identity and citizenship are being reshaped in cross-border areas following the implementation of European Union Cross Border Cooperation (CBC) programmes, with reference to the Upper Adriatic area. First, it offers a brief theoretical background on citizenship. Second, it investigates how different cross-border grass-roots stakeholders relate to each other in the process of implementing CBC projects and how, through their interaction, construct new meanings, interests and values and revisit their identities. It concludes by arguing that the constant interaction between societal and political cross-border actors at the local elite level is leading to greater mutual understanding, long-term transnational initiatives and an increasing emphasis on shared interests and values.
Immigrant population in Italy during the first decade of the 21st century: changing demographics and modified settlement patterns
Authors: Tragaki Alexandra , Rovolis Antonios
Published: July 2012

Changing demographics and modified settlement patterns have reshaped the socio-economic context of Southern Europe at the turn of the century. Within this context, Italy has become one of the major European destinations for migrants; their numbers have more than tripled during the years 2000–2010. This paper analyses the changing demography of (legal) migrants to Italy, as well as their settlement patterns and spatial distribution over time. Since the onset of the new millennium, immigrant populations in Southern Europe in general, and in Italy in particular, have been experiencing rapidly increasing volumes and rapidly changing demographics. The feminization of foreign population, its changing age structure and ethnic composition are some of the most striking features. Meanwhile, noteworthy changes have been registered in the spatial distribution of immigrants. Different ethnic groups follow different settlement patterns and register different levels of spatial dispersion. Though the migrant population in Italy remains more concentrated in the north, disparities between north–centre and south have decreased over the last decade. Analysis at a lower spatial level (Nomenclature of Units for Territorial Statistics level 3) shows a higher variability across time and counties, partly due to a changing ethnic composition and the increased numbers of immigrants.
Territorial attachment in the age of globalization: The case of Western Europe
Authors: Antonsich Marco , Holland Edward C.
Published: July 2012

The age of globalization has often been associated with de-/re-territorialization processes. The increasing integration of markets and the appearance of new modes of economic production and capital accumulation on the one hand, and the transformation of forms of political governance on the other, have led to the emergence of new territorial actors at the supra-national and sub-national scales. While these economic and political de-/re-territorialization processes have been studied at length, relatively little attention has been paid to the transformation of the territorial identities associated with these spaces. The aim of the present study is twofold. First, it aims to understand whether territorial identities are experiencing a similar re-scaling along with modes of economic production and forms of political governance. Second, it explores which factors today explain the attachment of people to their territories. A descriptive analysis of Eurobarometer survey data for Western Europe reveals no signs of a re-scaling of territorial identities, pointing to a sort of inertia of these identities in relation to the changing of political and economic structures. A statistical model on four scales of territorial attachment (local, regional, national and European) shows the complexity of its formation, as both personal compositional and regional contextual factors should be taken into account.
The experience turn as ‘bandwagon’: Understanding network formation and innovation as practice
Authors: Fuglsang Lars , Eide Dorthe
Published: July 2012

This paper uses the bandwagon metaphor to analyse, in two rural contexts, how small tourism firms become engaged in the idea of the experience economy and how the idea is turned into practice through network formation and innovation. In developing a practice-based approach we use the bandwagon metaphor to conceptualize network formation and innovation in terms of a ‘journey’. Following the practice-based literature on bandwagons, the journey starts by labelling an idea that is broad enough to give meaning to, and pull together, a number of diverse supporters. The journey also depends on two further central processes, namely appropriation and narrowing the workspace. One Norwegian and one Danish network are studied using a case methodology. They are two rural networks of mainly small tourism firms. The empirical study confirms and illustrates how the bandwagon effect involves these three core processes. However, we also argue for the importance of a fourth process, namely strategic reflexivity. The paper closes by suggesting a development model with relevance for policy. The paper offers an increased understanding of how the experience economy as an idea can become practice and puts forward a practice-based development model.
Val d’Europe: A pioneering turn to ‘experience’ planning?
Authors: d’Hauteserre Anne-Marie
Published: July 2012

French state planning grabbed the investment opportunity the Walt Disney Company offered in the 1980s when it was searching for a site for a European Disneyland. The French state needed to revive the development of the eastern Paris Basin towards the expanded European Union. Embracing the ‘experience’ know-how of the company, it pioneered the implementation of ‘experience planning’ to support the status of greater Paris as a global Metropolis. Aestheticisation, the hallmark of the experience turn of the economy was avoided for the city of Paris, yet materialities for cosmopolitan consumption were provided those willing to invest in Val d’Europe. The Walt Disney Company adapted its ‘experience’ knowledge to the urbanization of the area under the constraints of a Convention and its accompanying ‘planning project’, which determine all aspects and all phases of this land use development over 30 years. Collaboration between the experiential expertise of the Walt Disney Company and the vision and design of the French state has led to the effective and successful continuous emerging of a competitive yet liveable urban place.
A comparative classification of labour market characteristics of British and Greek small islands
Authors: Armstrong Harvey , Ballas Dimitris , Staines Adreene
Published: July 2012

There is a growing interest in island economies within Europe. In the European Union (EU) this has led to enhanced Cohesion Policy support for islands, along with a number of other regions facing geographical challenges. Because of major problems with data, comparative research on islands across different EU member states has been of limited extent. This paper explores the use of national data sets to undertake comparative cross-country analysis of islands. The paper concentrates on two member states, Greece and Britain, which have large numbers of offshore islands. Data from national population censuses are drawn upon to allow typologies of the islands to be developed. These typologies are utilised to identify similarities and differences between British and Greek islands.
Organisational obsessive– compulsive disorder: has clinical governance become pathological?
Authors: Bender Keith
Published: July 2012

Objective:

The aim of the study was to compare the use of various monitoring tools in the public psychiatry sector to the development of obsessive–compulsive rituals in individuals.

Conclusion:

The step from useful data collection to meaningless and incapacitating ritual may be prevented by the use of ongoing dialogue, assumption testing, realistic appraisal of clinician responsibility and tolerance of uncertainty.
Ready to Change: a scheduled telephone counselling programme for problem gambling
Authors: Rodda Simone , Lubman Dan
Published: July 2012

Objective:

This study describes the implementation of an innovative 4–6 week cognitive behavioural therapy (CBT) programme for problem gambling, Ready to Change (RTC), delivered via telephone and workbook.

Method:

Participants referred into the programme during the first three years of operation had a mean age of 45 years (range 19–81 years). The majority of participants were female (56%, n=129) and had problems associated with gaming machines (81.7%, n=188).

Results:

Between January 2008 and December 2010, 230 people were assessed and offered the RTC programme. The main reason for referral of a person into the programme was difficulty in accessing a face-to-face agency.

Conclusions:

We describe the components and challenges of a 4–6 week programme for the treatment of problem gambling delivered via telephone. While distance-based treatments address concerns over access to services, further research investigating their effectiveness is required.
Suicide attempts by jumping from a height: a consultation liaison experience
Authors: Gore-Jones Victoria , O’Callaghan John
Published: July 2012

Objective:

The purpose of this research was to study the demographic and clinical characteristics of a group of patients who attempted suicide by jumping from a height and sustained injuries that required hospitalisation.

Method:

Participants were patients who were admitted to a large tertiary hospital in Brisbane City following a suicide attempt. Patients received treatment-as-usual and their hospital files were audited retrospectively.

Results:

The patient profile was of a 31-year-old single person with a diagnosis of either a psychotic illness or borderline personality disorder. Sixty percent had prior contact with a mental health service and nearly three-quarters had made a previous attempt. Eighty percent reported the attempt was impulsive and nearly three-quarters reported having suicidal intent. The majority of attempts were precipitated by interpersonal stressors. Spinal injuries were the most common result.

Conclusions:

Practical implications include the role of interpersonal stressors as treatment targets. The impulsive nature of the attempt also raises the issue of physical barriers to deter suicide attempts by jumping from a height.
Enhancement of a tuned mass damper for building structures using fuzzy logic
Authors: Edalath Sanooj , Kukreti Anant R , Cohen Kelly
Published: July 2012

Over the past 10 years there has been a growing need to introduce closed-loop control technology for vibration suppression of buildings subject to wind or earthquake disturbances. This paper deals with the investigation of the effectiveness of a fuzzy logic based time variable damping tuned mass damper (TMD) on a building structure undergoing free and forced vibrations. The uniqueness of this approach is the application of a robust, nonlinear fuzzy based controller to emulate a time-optimal control strategy. Fuzzy logic based time variable damping is introduced into a semi-active TMD in order to enhance its performance in the vibration suppression of buildings. First, a single story structure for three different vibration suppression approaches is studied. The fuzzy logic based time variable damping TMD (fuzzy TMD) is compared to the baseline passive TMD as well as a conventional proportional-derivative (PD) controller. Forced vibration is introduced using a resonant harmonic sinusoidal excitation (i.e. same frequency as the fundamental frequency of the structure). Finally, the fuzzy TMD is compared to the baseline for the free vibration of a 15 story structure. For both structures studied, MATLAB® based simulation results show that the passive TMD and the PD, both constant gain approaches, provide similar results whereas the fuzzy TMD yields half the settling time. This effort clearly demonstrates the potential of a variable gain (damping) strategy for the vibration suppression of buildings.
A new impulsive synchronization of Chen hyper-chaotic system and Lü hyper-chaotic system
Authors: Zhao Jiakun , Zhou Di , Li Yexin
Published: July 2012

This work presents an impulsive synchronization scheme of the Chen hyper-chaotic system and L ü hyper-chaotic system with the assumption that all of the parameters are unknown. Sufficient conditions are derived, based on the impulsive differential stability theory, for achieving the impulsive synchronization with the desired scaling factor. By the adaptive control technique, the control laws and the corresponding parameter update laws are obtained such that the impulsive synchronization of the two non-identical hyper-chaotic systems can be realized. Simulation results also illustrate the effectiveness of the proposed control scheme.
Queerious youth: An empirical study of a queer youth cultural festival and its participants
Authors: Taylor Jodie
Published: July 2012

Various institutional legacies and contemporary social circumstances often work to constrain the voices and cultural expressions of gender and sexually diverse young people. However, gender and sexually diverse youth can also respond critically and creatively, generating their own sites of cultural participation and meaning. Through an empirical case study of Queeriosity – a queer youth cultural festival held in Brisbane, Australia – this article details the impetus behind the creation of this youth-led event. Second, drawing on participant observations and survey data collected at the festival, this article provides a ‘snapshot’ of the various identities, attitudes and cultural styles that circulate within Brisbane’s queer youth communities. Finally, it argues that the spectacle, celebration and diverse articulations of youth sexualities which underpinned Queeriosity provided participants with opportunities for sexual self-making.
Education about dementia in primary care: Is person-centredness the key?
Authors: Edwards Rachel , Voss Sarah , Iliffe Steve
Published: July 2012

Primary care is ideally placed to recognise and manage dementia and yet dementia can be overlooked or misattributed by primary care practitioners and is underdiagnosed. This might be explained by a lack of formal training in the diagnosis of dementia combined with a reluctance to diagnose due to its associated stigma. This paper describes focus group work with service users, carers and health professionals, conducted to develop an educational intervention for primary care promoting person-centred responses to people experiencing cognitive decline and dementia. Data was analysed thematically and four themes emerged: Reframing dementia as cognitive decline (Individual level); triggers for the recognition of dementia (Practitioner level); engaging the whole primary care team (Practice level); the relationship between primary and secondary care (Service level). Findings are discussed in the context of their contribution to challenging attitudes to dementia in primary care and the positive aspects of person-centred primary care for dementia.
Approximate homomorphisms and derivations on random Banach algebras
Authors: Madadian M , Ebadian A , Eshaghi Gordji M , Azadi Kenary H
Published: July 2012

The motivation of this paper is to investigate the stability of homomorphisms and derivations on random Banach algebras.

MSC:39B82, 39B52.
Protein-protein binding site identification by enumerating the configurations
Authors: Guo Fei , Li Shuai Cheng , Wang Lusheng , Zhu Daming
Published: July 2012

Background

The ability to predict protein-protein binding sites has a wide range of applications, including signal transduction studies, de novo drug design, structure identification and comparison of functional sites. The interface in a complex involves two structurally matched protein subunits, and the binding sites can be predicted by identifying structural matches at protein surfaces.

Results

We propose a method which enumerates “all” the configurations (or poses) between two proteins (3D coordinates of the two subunits in a complex) and evaluates each configuration by the interaction between its components using the Atomic Contact Energy function. The enumeration is achieved efficiently by exploring a set of rigid transformations. Our approach incorporates a surface identification technique and a method for avoiding clashes of two subunits when computing rigid transformations. When the optimal transformations according to the Atomic Contact Energy function are identified, the corresponding binding sites are given as predictions. Our results show that this approach consistently performs better than other methods in binding site identification.

Conclusions

Our method achieved a success rate higher than other methods, with the prediction quality improved in terms of both accuracy and coverage. Moreover, our method is being able to predict the configurations of two binding proteins, where most of other methods predict only the binding sites. The software package is available athttp://sites.google.com/site/guofeics/dobifor non-commercial use.
Functional characterization and evolution of PTH/PTHrP receptors: insights from the chicken
Authors: Pinheiro Pedro LC , Cardoso João CR , Power Deborah M , Canário Adelino V M
Published: July 2012

Background

The parathyroid hormone (PTH)-family consists of a group of structurally related factors that regulate calcium and bone homeostasis and are also involved in development of organs such as the heart, mammary gland and immune system. They interact with specific members of family 2 B1 G-protein coupled receptors (GPCRs), which have been characterised in teleosts and mammals. Two PTH/PTHrP receptors, PTH1R and PTH2R exist in mammals and in teleost fish a further receptor PTH3R has also been identified. Recently in chicken, PTH-family members involved in calcium transport were characterized and specific PTHRs are suggested to exist although they have not yet been isolated or functionally characterized. The aim of this study is to further explore the evolution and function of the vertebrate PTH/PTHrP system through the isolation, phylogenetic analysis and functional characterization of the chicken receptors.

Results

Two PTHRs were isolated in chicken and sequence comparison and phylogenetic analysis indicate that the chicken receptors correspond to PTH1R and PTH3R, which emerged prior to the teleost/tetrapod divergence since they are present in cartilaginous fish. The vertebrate PTH2R receptor and its ligand TIP39 have been lost from bird genomes. Chicken PTH1R and PTH3R have a divergent and widespread tissue expression and are also evident in very early embryonic stages of development. Receptor stimulation studies using HEK293 cells stably expressing the chicken PTH1R and PTH3R and monitoring cAMP production revealed they are activated by chicken 1–34 N-terminal PTH-family peptides in a dose dependent manner. PTH-L and PTHrP were the most effective peptides in activating PTH1R (EC50 = 7.7 nM and EC50 = 22.7 nM, respectively). In contrast, PTH-L (100 nM) produced a small cAMP accumulation on activation of PTH3R but PTHrP and PTH (EC50 = 2.5 nM and EC50 = 22.1 nM, respectively) readily activated the receptor. PTHrP also stimulated intracellular Ca2+ accumulation on activation of PTH1R but not PTH3R.

Conclusion

Two PTHR homologues of the vertebrate PTH1R and PTH3R were isolated and functionally characterized in chicken. Their distinct pattern of expression during embryo development and in adult tissues, together with their ligand preference, suggests that they have acquired specific functions, which have contributed to their maintenance in the genome. PTH2R and its activating ligand, TIP39, are absent from bird genomes. Nonetheless identification of putative PTH2R and TIP39 in the genome of an ancient agnathan, lamprey, suggests the PTH/PTHrP ligand and receptor family was already present in an early basal paraphyletic group of vertebrates and during the vertebrate radiation diverged via gene/genome duplication and deletion events. Knowledge of the role PTH/PTHrP system in early vertebrates will help to establish evolution of function.
Duplicate gene evolution, homoeologous recombination, and transcriptome characterization in allopolyploid cotton
Authors: Flagel Lex E , Wendel Jonathan F , Udall Joshua A
Published: July 2012

Background

Modern allotetraploid cotton contains an “A” and “D” genome from an ancestral polyploidy event that occurred approximately 1–2 million years ago. Diploid A- and D-genome species can be compared to the A- and D-genomes found within these allotetraploids to make evolutionary inferences about polyploidy. In this paper we present a comprehensive EST assembly derived from diploid and model allotetraploid cottons and demonstrate several evolutionary inferences regarding genic evolution that can be drawn from these data.

Results

We generated a set of cotton expressed sequence tags (ESTs), comprising approximately 4.4 million Sanger and next-generation (454) transcripts supplemented by approximately 152 million Illumina reads from diploid and allotetraploid cottons. From the EST alignments we inferred 259,192 genome-specific single nucleotide polymorphisms (SNPs). Molecular evolutionary analyses of protein-coding regions demonstrate that the rate of nucleotide substitution has increased among both allotetraploid genomes relative to the diploids, and that the ratio of nonsynonymous to synonymous substitutions has increased in one of the two polyploid lineages we sampled. We also use these SNPs to show that a surprisingly high percentage of duplicate genes (~7 %) show a signature of non-independent evolution in the allotetraploid nucleus, having experienced one or more episodes of nonreciprocal homoeologous recombination (NRHR).

Conclusions

In this study we characterize the functional and mutational properties of the cotton transcriptome, produce a large genome-specific SNP database, and detect illegitimate genetic exchanges between duplicate genomes sharing a common allotetraploid nucleus. Our findings have important implications for our understanding of the consequences of polyploidy and duplicate gene evolution. We demonstrate that cotton genes have experienced an increased rate of molecular evolution following duplication by polyploidy, and that polyploidy has enabled considerable levels of nonreciprocal exchange between homoeologous genes.
hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions
Authors: Silva Tanielly Cristina Raiol , Leal Mariana Ferreira , Calcagno Danielle Queiroz , de Souza Carolina Rosal Teixeira , Khayat André Salim , dos Santos Ney Pereira Carneiro , Montenegro Raquel Carvalho , Rabenhorst Silvia Helena Barem , Nascimento Mayara Quaresma , Assumpção Paulo Pimentel , de Arruda Cardoso Smith Marília , Burbano Rommel Rodríguez
Published: July 2012

Background

Gastric cancer is a serious public health problem in Northern Brazil and in the world due to its high incidence and mortality. Despite the severity of the disease, more research is needed to better understand the molecular events involved in this intestinal-type gastric carcinogenesis process. Since precancerous lesions precede intestinal-type gastric cancer, here, we evaluated the hTERT, MYC, and TP53 mRNA and protein expression, as well as TP33 copy number, in gastric preneoplastic lesions.

Methods

We evaluated 19 superficial gastritis, 18 atrophic gastritis, and 18 intestinal metaplasia from cancer-free individuals of Northern Brazil. Quantitative reverse transcription PCR was used to analyze the mRNA expression and immunohistochemical methods were used to assess protein immunoreactivity in tissue samples. The number of TP53 gene copies was investigated in gastric diseases by quantitative PCR.

Results

We observed hTERT, MYC, and p53 immunoreactivity only in intestinal metaplasia samples. The immunoreactivity of these proteins was strongly associated with each other. A significantly higher MYC mRNA expression was observed in intestinal metaplasia compared to gastritis samples. Loss of TP53 was also only detected in intestinal metaplasia specimens.

Conclusions

We demonstrated that hTERT, MYC, and TP53 are deregulated in intestinal metaplasia of individuals from Northern Brazil and these alterations may facilitate tumor initiation.
Different fatty acid metabolism effects of (−)-Epigallocatechin-3-Gallate and C75 in Adenocarcinoma lung cancer
Authors: Relat Joana , Blancafort Adriana , Oliveras Glòria , Cufí Sílvia , Haro Diego , Marrero Pedro F , Puig Teresa
Published: July 2012

Background

Fatty acid synthase (FASN) is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (−)-epigallocatechin-3-gallate (EGCG) in a lung cancer model.

Methods

We evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes), cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR) in human A549 lung carcinoma cells. In vivo, we evaluated their anti-tumour activity and their effect on body weight in a mice model of human adenocarcinoma xenograft.

Results

C75 and EGCG had comparable effects in blocking FASN activity (96,9% and 89,3% of inhibition, respectively). In contrast, EGCG had either no significant effect in CPT activity, the rate-limiting enzyme of fatty acid β-oxidation, while C75 stimulated CPT up to 130%. Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling. While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss.

Conclusions

In lung cancer, inhibition of FASN using EGCG can be achieved without parallel stimulation of fatty acid oxidation and this effect is related mainly to EGFR signaling pathway. EGCG reduce the growth of adenocarcinoma human lung cancer xenografts without inducing body weight loss. Taken together, EGCG may be a candidate for future pre-clinical development.
Effects of particulate matter on inflammatory markers in the general adult population
Authors: Tsai Dai-Hua , Amyai Nadia , Marques-Vidal Pedro , Wang Jia-Lin , Riediker Michael , Mooser Vincent , Paccaud Fred , Waeber Gerard , Vollenweider Peter , Bochud Murielle
Published: July 2012

Background

Particulate air pollution is associated with increased risk of cardiovascular disease and stroke. Although the precise mechanisms underlying this association are still unclear, the induction of systemic inflammation following particle inhalation represents a plausible mechanistic pathway.

Methods

We used baseline data from the CoLaus Study including 6183 adult participants residing in Lausanne, Switzerland. We analyzed the association of short-term exposure to PM10 (on the day of examination visit) with continuous circulating serum levels of high-sensitive C-reactive protein (hs-CRP), interleukin 1-beta (IL-1β), interleukin 6 (IL-6), and tumor-necrosis-factor alpha (TNF-α) by robust linear regressions, controlling for potential confounding factors and assessing effect modification.

Results

In adjusted analyses, for every 10 μg/m3 elevation in PM10, IL-1ß increased by 0.034 (95 % confidence interval, 0.007-0.060) pg/mL, IL-6 by 0.036 (0.015-0.057) pg/mL, and TNF-α by 0.024 (0.013-0.035) pg/mL, whereas no significant association was found with hs-CRP levels.

Conclusions

Short-term exposure to PM10 was positively associated with higher levels of circulating IL-1ß, IL-6 and TNF-α in the adult general population. This positive association suggests a link between air pollution and cardiovascular risk, although further studies are needed to clarify the mechanistic pathway linking PM10 to cardiovascular risk.
Plenary Perspective: The complexity of constitutive and inducible gene expression in mononuclear phagocytes
Authors: Hume David A
Published: July 2012

2011 SLB Bonazinga Award Winner: Perspective on the impact of genome-scale technologies on our understanding of macrophage biology, and the evolution of innate immune cell function.

Monocytes and macrophages differentiate from progenitor cells under the influence of colony-stimulating factors. Genome-scale data have enabled the identification of the set of genes that distinguishes macrophages from other cell types and the ways in which thousands of genes are regulated in response to pathogen challenge. Although there has been a focus on a small subset of lineage-enriched transcription factors, such as PU.1, more than one-half of the transcription factors in the genome can be expressed in macrophage lineage cells under some state of activation, and they interact in a complex network. The network architecture is conserved across species, but many of the target genes evolve rapidly and differ between mouse and human. The data and publication deluge related to macrophage biology require the development of new analytical tools and ways of presenting information in an accessible form. The website http://www.macrophages.com is a community website that partly fills this niche.
Time-reversal checkpointing methods for RTM and FWI
Authors: Anderson John E. , Tan Lijian , Wang Don
Published: July 2012

Time-domain seismic simulation can form the basis of reverse time depth migration and full-waveform inversion. These applications need to temporally crosscorrelate a forward simulation state with an adjoint simulation state and therefore need to be able to access each time step of a forward simulation in time-reverse order. This requires saving all forward states for all times (which can require more memory than is typically available on a computer system for many problems of interest), or the ability to checkpoint information and rapidly recompute forward simulation states as needed. Prior work has suggested how to do the latter by optimally choosing which forward simulation time steps to checkpoint, thereby enabling the most efficient reuse of memory buffers and minimizing recomputation. The optimal trade-off between memory usage and recomputation can be further improved under the assumption that the information needed to do temporal crosscorrelation is smaller than the information required to restart a simulation from a given time step. This assumption is true for many geophysical problems of interest. The modification can yield a reduction in the memory requirement and recomputation time. The tested examples applied to isotropic elastic reverse time migration and anisotropic viscoelastic full-waveform inversion.
3D finite-difference modeling of elastic wave propagation in the Laplace-Fourier domain
Authors: Petrov Petr V. , Newman Gregory A.
Published: July 2012

With the recent interest in the Laplace-Fourier domain full waveform inversion, we have developed new heterogeneous 3D fourth- and second-order staggered-grid finite-difference schemes for modeling seismic wave propagation in the Laplace-Fourier domain. Our approach is based on the integro-interpolation technique for the velocity-stress formulation in the Cartesian coordinate system. Five averaging elastic coefficients and three averaging densities are necessary to describe the heterogeneous medium, with harmonic averaging of the bulk and shear moduli, and arithmetic averaging of density. In the fourth-order approximation, we improved the accuracy of the scheme using a combination of integral identities for two elementary volumes — “small” and “large” around spatial gridpoints where the wave variables are defined. Two solution approaches are provided, both of which are solved with iterative Krylov methods. In the first approach, the stress variables are eliminated and a linear system for the velocity components is solved. In the second approach, we worked directly with the first-order system of velocity and stress variables. This reduced the computer memory required to store the complex matrix, along with reducing (by 30%) the number of arithmetic operations needed for the solution compared to the fourth-order scheme for velocity only. Numerical examples show that our finite-difference formulations for elastic wavefield simulations can achieve more accurate solutions with fewer grid points than those from previously published second and fourth-order frequency-domain schemes. We applied our simulator to the investigation of wavefields from the SEG/EAGE model in the Laplace-Fourier domain. The calculation is sensitive to the heterogeneity of the medium and capable of describing the structures of complex objects. Our technique can also be extended to 3D elastic modeling within the time domain.
Precise inversion of logged slownesses for elastic parameters in a gas shale formation
Authors: Miller Douglas E. , Horne Steve A. , Walsh John
Published: July 2012

Dipole sonic log data recorded in a vertical pilot well and the associated production well are analyzed over a [Formula: see text]-ft section of a North American gas shale formation. The combination of these two wells enables angular sampling in the vertical direction and over a range of inclination angles from 54° to 90°. Dipole sonic logs from these wells show that the formation’s average properties are, to a very good approximation, explained by a transversely isotropic medium with a vertical symmetry axis and with elastic parameters satisfying [Formula: see text], but inconsistent with the additional ANNIE relation ([Formula: see text]). More importantly, these data clearly show that, at least for fast anisotropic formations such as this gas shale, sonic logs measure group slownesses for propagation with the group angle equal to the borehole inclination angle. Conversely, the data are inconsistent with an interpretation that they measure phase slownesses for propagation with the phase angle equal to the borehole inclination angle.
Instantaneous phase variation for seismic velocity monitoring from ambient noise at the exploration scale
Authors: Corciulo Margherita , Roux Philippe , Campillo Michel , Dubucq Dominique
Published: July 2012

Recent studies in geophysics have investigated the use of seismic-noise correlations to measure weak-velocity variations from seismic-noise recordings. However, classically, the existing algorithms used to monitor medium velocities need extensive efforts in terms of computation time. This implies that these techniques are not appropriate at smaller scales in an exploration context when continuous data sets on dense arrays of sensors have to be analyzed. We applied a faster technique that allows the monitoring of small velocity changes from the instantaneous phase measurement of the seismic-noise crosscorrelation functions. We performed comparisons with existing algorithms using synthetic signals. The results we have obtained for a real data set show that the statistical distribution of the velocity-change estimates provides reliable measurements, despite the low signal-to-noise ratio obtained from the noise-correlation process.
Image-guided sparse-model full waveform inversion
Authors: Ma Yong , Hale Dave , Gong Bin , Meng Zhaobo (Joe)
Published: July 2012

Multiple problems, including high computational cost, spurious local minima, and solutions with no geologic sense, have prevented widespread application of full waveform inversion (FWI), especially FWI of seismic reflections. These problems are fundamentally related to a large number of model parameters and to the absence of low frequencies in recorded seismograms. Instead of inverting for all the parameters in a dense model, image-guided full waveform inversion inverts for a sparse model space that contains far fewer parameters. We represent a model with a sparse set of values, and from these values, we use image-guided interpolation (IGI) and its adjoint operator to compute finely and uniformly sampled models that can fit recorded data in FWI. Because of this sparse representation, image-guided FWI updates more blocky models, and this blockiness in the model space mitigates the absence of low frequencies in recorded data. Moreover, IGI honors imaged structures, so image-guided FWI built in this way yields models that are geologically sensible.
Blended acquisition with dispersed source arrays
Authors: Berkhout A. J.
Published: July 2012

Blended source arrays are historically configured with equal source units, such as broadband vibrators (land) and broadband air-gun arrays (marine). I refer to this concept as homogeneous blending. I have proposed to extend the blending concept to inhomogeneous blending, meaning that a blended source array consists of different source units. More specifically, I proposed to replace in blended acquisition the traditional broadband sources by narrowband versions — imagine coded single air guns with different volumes or coded single narrowband vibrators with different central frequencies — together representing a dispersed source array (DSA). Similar to what we see in today’s audio systems, the DSA concept allows the design of dedicated narrowband source elements that do not suffer from the low versus high frequency compromise. In addition, the DSA concept opens the possibility to use source depths and spatial sampling intervals that are optimum for the low-, mid-, and high-frequency sources (multiscale shooting grids). DSAs are considered to be an important step in robotizing the seismic acquisition process.
Proteomic analysis of multiple primary cilia reveals a novel mode of ciliary development in mammals
Authors: Narita Keishi , Kozuka-Hata Hiroko , Nonami Yuta , Ao-Kondo Hiroko , Suzuki Toshimitsu , Nakamura Hideki , Yamakawa Kazuhiro , Oyama Masaaki , Inoue Takafumi , Takeda Sen
Published: July 2012

Cilia are structurally and functionally diverse organelles, whose malfunction leads to ciliopathies. While recent studies have uncovered common ciliary transport mechanisms, limited information is available on the proteome of cilia, particularly that of sensory subtypes, which could provide insight into their functional and developmental diversities. In the present study, we performed proteomic analysis of unique, multiple 9+0 cilia in choroid plexus epithelial cells (CPECs). The analysis of juvenile swine CPEC cilia identified 868 proteins. Among them, 396 were shared with the proteome of 9+0 photoreceptor cilia (outer segment), whereas only 152 were shared with the proteome of 9+2 cilia and flagella. Various signaling molecules were enriched in a CPEC-specific ciliome subset, implicating multiplicity of sensory functions. The ciliome also included molecules for ciliary motility such as Rsph9. In CPECs from juvenile swine or adult mouse, Rsph9 was localized to a subpopulation of cilia, whereas they were non-motile. Live imaging of mouse choroid plexus revealed that neonatal CPEC cilia could beat vigorously, and the motility waned and was lost within 1–2 weeks. The beating characteristics of neonatal CPEC cilia were variable and different from those of typical 9+2 cilia of ependyma, yet an Efhc1-mediated mechanism to regulate the beating frequency was shared in both types of cilia. Notably, ultrastructural analysis revealed the presence of not only 9+0 but also 9+2 and atypical ciliary subtypes in neonatal CPEC. Overall, these results identified both conserved and variable components of sensory cilia, and demonstrated a novel mode of ciliary development in mammals.
Calsyntenin-1 shelters APP from proteolytic processing during anterograde axonal transport
Authors: Steuble Martin , Diep Tu-My , Schätzle Philipp , Ludwig Alexander , Tagaya Mitsuo , Kunz Beat , Sonderegger Peter
Published: July 2012

Endocytosis of amyloid-β precursor protein (APP) is thought to represent the major source of substrate for the production of the amyloidogenic Aβ peptide by the β-secretase BACE1. The irreversible nature of proteolytic cleavage implies the existence of an efficient replenishment route for APP from its sites of synthesis to the cell surface. We recently found that APP exits the trans-Golgi network in intimate association with calsyntenin-1, a transmembrane cargo-docking protein for Kinesin-1-mediated vesicular transport. Here we characterized the function of calsyntenin-1 in neuronal APP transport using selective immunoisolation of intracellular trafficking organelles, immunocytochemistry, live-imaging, and RNAi. We found that APP is co-transported with calsyntenin-1 along axons to early endosomes in the central region of growth cones in carriers that exclude the α-secretase ADAM10. Intriguingly, calsyntenin-1/APP organelles contained BACE1, suggesting premature cleavage of APP along its anterograde path. However, we found that APP contained in calsyntenin-1/APP organelles was stable. We further analyzed vesicular trafficking of APP in cultured hippocampal neurons, in which calsyntenin-1 was reduced by RNAi. We found a markedly increased co-localization of APP and ADAM10 in axons and growth cones, along with increased proteolytic processing of APP and Aβ secretion in these neurons. This suggested that the reduced capacity for calsyntenin-1-dependent APP transport resulted in mis-sorting of APP into additional axonal carriers and, therefore, the premature encounter of unprotected APP with its ectodomain proteases. In combination, our results characterize calsyntenin-1/APP organelles as carriers for sheltered anterograde axonal transport of APP.
The residence time of focal adhesion kinase (FAK) and paxillin at focal adhesions in renal epithelial cells is determined by adhesion size, strength and life cycle status.
Authors: Le Dévédec Sylvia E. , Geverts Bart , de Bont Hans , Yan Kuan , Verbeek Fons J. , Houtsmuller Adriaan B. , van de Water Bob
Published: July 2012

Focal adhesions (FAs) are specialized membrane associated multi-protein complexes that link the cell to the extra-cellular matrix and enable cell proliferation, survival, and motility. Despite the extensive description of the molecular composition of FAs, the complex regulation of FA dynamics is largely unclear. Here, we have applied photobleaching assays on the whole cell to allow the determination of protein dynamics in every single focal adhesion. We identified that the focal adhesion proteins FAK and paxillin exist in two different states: a diffusive cytoplasmic pool and a transiently immobile FA-bound fraction with variable residence times. Interestingly, the average residence time of both proteins increased with focal adhesion size. Moreover, increasing integrin clustering by modulating surface collagen density increased residence time of FAK but not paxillin. Finally, this approach was applied to measure FAK and paxillin dynamics using nocodazole treatment followed by washout. This revealed an opposite residence time of FAK and paxillin in maturing and disassembling FAs, which depends on the ventral and peripheral cellular position of the FAs.
A novel mechanism of control of NFκB activation and inflammation involving A2B adenosine receptors
Authors: Sun Ying , Duan Yuanyuan , Eisenstein Anna S. , Hu Wenbao , Quintana Adrien , Lam Wai Kwan , Wang Yan , Wu Zhenguo , Ravid Katya , Huang Pingbo
Published: July 2012

The NFκB pathway controls a variety of process, including inflammation, and thus, the regulation of NFκB has been a continued focus of study. Here, we report a newly identified regulation of this pathway, involving direct binding of the transcription factor NFκB1/p105 to the C-terminus of the A2B adenosine receptor (A2BAR), independent of ligand activation. Intriguingly, binding of A2BAR to specific sites on p105 prevents polyubiquitination and degradation of p105 protein. Ectopic expression of the A2BAR increases p105 levels and inhibits NFκB activation, while p105 protein levels are reduced in cells from A2BAR knockout mice. In accordance with the known regulation of expression of anti- and pro-inflammatory cytokines by p105, A2BAR null mice generate less IL-10, and more IL-12 and TNF-α. Taken together, our results show that the A2BAR inhibits NFκB activation by physically interacting with p105, thereby blocking its polyubiquitination and degradation. Our findings unveil a surprising function for the A2BAR, and provide a novel mechanistic insight into the control of the NFκB pathway and inflammation.
Post-mitotic dynamics of pre-nucleolar bodies is driven by pre-ribosomal RNA processing
Authors: Carron Coralie , Balor Stéphanie , Delavoie Franck , Plisson-Chastang Célia , Faubladier Marlène , Gleizes Pierre-Emmanuel , O'Donohue Marie-Françoise
Published: July 2012

Understanding the relationship linking the topological dynamics of nuclear subdomains to their molecular function is a central issue in nucleus biology. Pre-nucleolar bodies (PNBs) are transient nuclear subdomains, which form at telophase and contain nucleolar proteins, snoRNPs and pre-ribosomal RNAs (pre-rRNAs). These structures gradually disappear in early G1 phase and are currently seen as reservoirs of nucleolar factors that participate to post-mitotic reassembly of the nucleolus. Here, we provide evidence from FISH and loss-of-function experiments in HeLa cells that PNBs are in fact active ribosome factories in which maturation of the pre-rRNAs transiting through mitosis resumes at telophase. We show that the pre-rRNA spacers are sequentially removed in PNBs when cells enter G1 phase, indicating regular pre-rRNA processing as in the nucleolus. Accordingly, blocking pre-rRNA maturation induces accumulation in PNBs of stalled pre-ribosomes characterized by specific pre-rRNAs and pre-ribosomal factors. The presence of pre-ribosomal particles in PNBs is corroborated by observation of these domains with correlative electron tomography. Most importantly, blocking pre-rRNA maturation also prevents the gradual disappearance of PNBs, which persist for several hours in the nucleoplasm. In a revised model, we propose that PNBs are autonomous extra-nucleolar ribosome maturation sites, whose orderly disassembly in G1 phase is driven by the maturation and release of their pre-ribosome content.