bluuebunny/crossref_metadata_2025 huggingface dataset:
High Performance Development for High End Computing With Python Language Wrapper (PLW)
Authors: Luszczek Piotr , Dongarra Jack
Published: July 2007

This paper presents a design and implementation of a system that leverages interactive scripting environment to the needs of scientific computing. The system allows seamless translation of high level script codes to highly optimized native language executables that can be ported to parallel systems with high performance hardware and potential lack of the scripting language interpreter. Performance results are given to show various usage scenarios that differ in terms of invested programmer's effort and resulting performance gains.
'pMATLAB Parallel MATLAB Library'
Authors: Travinin Bliss N. , Kepner J.
Published: July 2007

MATLAB® has emerged as one of the languages most commonly used by scientists and engineers for technical computing, with approximately one million users worldwide. The primary benefits of MATLAB are reduced code development time via high levels of abstractions (e.g. first class multi-dimensional arrays and thousands of built in functions), interpretive, interactive programming, and powerful mathematical graphics. The compute intensive nature of technical computing means that many MATLAB users have codes that can significantly benefit from the increased performance offered by parallel computing. pMatlab provides this capability by implementing parallel global array semantics using standard operator overloading techniques. The core data structure in pMatlab is a distributed numerical array whose distribution onto multiple processors is specified with a “map” construct. Communication operations between distributed arrays are abstracted away from the user and pMatlab transparently supports redistribution between any block-cyclic-overlapped distributions up to four dimensions. pMatlab is built on top of the MatlabMPI communication library and runs on any combination of heterogeneous systems that support MATLAB, which includes Windows, Linux, MacOS X, and SunOS. This paper describes the overall design and architecture of the pMatlab implementation. Performance is validated by implementing the HPC Challenge benchmark suite and comparing pMatlab performance with the equivalent C+MPI codes. These results indicate that pMatlab can often achieve comparable performance to C+MPI, usually at one tenth the code size. Finally, we present implementation data collected from a sample of real pMatlab applications drawn from the approximately one hundred users at MIT Lincoln Laboratory. These data indicate that users are typically able to go from a serial code to an efficient pMatlab code in about 3 hours while changing less than 1% of their code.
A Very Private Business
Authors: Anderson Bridget
Published: July 2007

This article considers whether there is a specific demand for migrant domestic workers in the UK, or for workers with particular characteristics that in theory could be met by citizens. It discusses how immigration status can make it easier not only to recruit domestic workers, but also to retain them. `Foreignness' may also make the management of the employment relation easier with employers anxious to discover a coincidence of interest with the worker. Employers are not only looking for generic `foreignness' however, but typically also seek particular nationalities or ethnicities of worker, which can raise difficulties for agencies who are not allowed to discriminate on the basis of `race'.
The Invisible Carers
Authors: Peterson Elin
Published: July 2007

This article explores how paid domestic work is framed in state policies and discourses, drawing upon theoretical discussions on gender, welfare and global care chains. Based on a case study of the political debate on the `reconciliation of personal, family and work life' in Spain, the author argues that dominant policy frames relate gender inequality to women's unpaid domestic work and care, while domestic workers are essentially the invisible `other'. Empowering and disempowering frames are discussed; domestic workers are mainly constructed as a solution to the care problem and only marginally as subjects and rights-holders. The overall aim is to examine how public policies legitimize and (re)produce social inequalities related to gender, class and nationality.
The Au Pair Body
Authors: Cox Rosie
Published: July 2007

The employment of au pairs to provide childcare, cleaning and other domestic services has been steadily increasing in the UK. This article provides an analysis of representations of au pairs in the British press and on the websites of agencies placing au pairs. This analysis seeks to understand how such imaginings of au pairs affect their life in Britain and how au pairs themselves respond to such imaginings. It argues that the competing portrayals of au pairs as both sexual sirens and committed carers works with other ambivalences in the scheme to facilitate the growth of au pair employment in Britain while simultaneously denying their place as an important source of domestic labour for British families.
Changes in and correlates of individual quality of life in advanced cancer patients admitted to an academic unit for palliative care
Authors: Echteld Michael A , van Zuylen Lia , Bannink Marjolein , Witkamp Erica , Van der Rijt Carin CD
Published: July 2007

Changes in individual quality of life (IQoL) and its correlates in patients admitted to an academic palliative care unit are reported. Correlates tested were pain, fatigue, and reconceptualization (changes in content of quality of life, a measure of adaptation). IQoL was measured with a structured interview method that derives an IQoL score from evaluations of individually nominated life areas. Twenty-nine patients were included in the study and interviewed shortly after unit admission. Sixteen patients were interviewed before discharge (more than 1 week between interviews). The results show that mean IQoL scores improved notably. Pain and IQoL correlated negatively and moderately at admission, and correlations between fatigue and pain at discharge and IQoL were negative and strong. An increasing number of changes in life areas was moderately associated with worsening IQoL. Life area's most often nominated were relationships with family members and friends, symptoms and aspects related to maintaining control. Palliative Medicine 2007; 21: 199—205
Applying corpus-based findings to form-focused instruction: The case of reported speech
Authors: Barbieri Federica , Eckhardt Suzanne E.B.
Published: July 2007

Arguing that the introduction of corpus linguistics in teaching materials and the language classroom should be informed by theories and principles of SLA, this paper presents a case study illustrating how corpus-based findings on reported speech can be integrated into a form-focused model of instruction. After overviewing previous work which compares ESL grammar textbooks descriptions and real language use, and promotes the use of corpus-based findings to inform L2 textbook descriptions, we outline the results of a survey of the presentation of reported speech in current popular textbooks. The survey findings are contrasted with the patterns of use found in two corpus-based cross-register studies of reported speech, showing how textbooks neglect important information on the use of this structure in real language. The frequency patterns of use that emerged in the corpus studies are then used to identify 10 principles that should inform the design of L2 materials and classroom instruction of reported speech. In the second part of the paper we illustrate how corpus-based findings can be fruitfully implemented in a form-focused model of instruction through the use of structure-based tasks and selected principles of focus-on-form.
The news about comedy
Authors: Feldman Lauren
Published: July 2007

Recent survey data suggest that at the same time as young Americans are abandoning traditional news media, they are more likely to identify late-night comedy programs, particularly Comedy Central's The Daily Show with Jon Stewart, as a destination for learning about election campaigns. In order to explore how journalists are responding to the idea of a comedy program as a news source, this article analyzes discourse about The Daily Show as it appeared in the trade and popular presses between January 1999 and March 2004. Emerging from this analysis is the way in which journalists are using The Daily Show as an occasion to reflect upon the nature of their work and the current state of their profession. For many journalists, The Daily Show has prompted reconsideration of the once rigid distinction between news and entertainment and of the historical conventions used to enforce this distinction.
Sports journalism
Authors: Rowe David
Published: July 2007

Sports journalism is an increasingly significant feature of the press yet is subject to considerable criticism, as summarized by the familiar jibe that it is the `toy department of the news media'. While there is an element of cultural snobbery and prejudice in this charge, sports journalism should not be exempted from scrutiny regarding conventional professional criteria within the news arena. There is, though, a dearth of empirical evidence concerning international patterns in sport. This article draws on data from the International Sports Press Survey 2005 (Schultz-Jorgensen, 2005), the largest international survey of sports journalism yet produced, and, in particular, on its Australian component. In assessing the survey's findings on sports journalism's concerns with problems and social issues, and the range of sources that it uses, the article reflects on whether the pejorative `toy department' is justified. In concluding it addresses the role of sports journalists in the creation, maintenance, and enhancement of a sports celebrity system.
More authentic than thou: Authenticity and othering in Fiji tourism discourse
Authors: White Carmen M.
Published: July 2007

This article explores the ways that othering and differentiation in Fiji tourism discourse cater to international tourists' presumed quest for authenticity. In addition to tapping into western discursive practices differentiating Polynesian and Melanesian `primitivity', Fiji tourism promoters market their destination as a site to experience the `genuine friendliness' of indigenous Fijians as the native, `authentic other'. `Genuine', is about `real' friendliness which, as a qualifier, also becomes a subtle reference to what other `others' that are also the focus of a western tourist gaze are relatively not. This process of differentiating indigenous Fijians from alternative others occurs internationally as an implicit albeit significant theme in Fiji tourism. Yet, differentiation also occurs domestically as indigenous Fijians become specificated as the group more `touristically marked' in Fiji, particularly in relation to Fiji Indians, whose erasure from tourism imagery is consistent with the prevailing themes of Fiji tourism discourse.
Meaning in the Maze: the heritage of Long Kesh
Authors: Graham Brian , McDowell Sara
Published: July 2007

The article examines the role of the former Long Kesh/Maze prison as one of the key heritage sites of the Northern Ireland conflict. It is grounded within the context of the political processes which have followed the implementation of the Belfast Peace Agreement in 1998. A brief history of the site and the salient points in its timeline precedes a discussion of the recommendations of the Maze Consultation Panel which reported in 2005. Among its principal proposals was the reconstruction of part of the Maze site as an International Centre for Conflict Transformation. The article examines the responses of various stakeholders to this idea but uses Sinn Féin's favoured analogies of Robben Island and, particularly, Auschwitz-Birkenau to conclude that only republicanism has a clearly defined sense of the heritage value of the Maze and an understanding as to how the site might be appropriated and exploited as an iconic place for remembering, contestation and resistance.
Salvage memory: constellating material histories on a hardscrabble homestead
Authors: DeSilvey Caitlin
Published: July 2007

The essay experiments with a process of recollection that moves associatively among the discarded material remains of a Montana homestead. Fragmentary objects and documents are brought into focus through their juxtaposition with each other, in an attempted recuperation of obsolete networks of use and affinity. A thread of oral history offers complement and counterpoint to the material histories. Shuttling between close description and critical reflection, the essay engages imaginatively with the cultural remembrance of private and public life in Depression-era Montana.
Beyond public protection
Authors: Kemshall Hazel , Wood Jason
Published: July 2007

Public protection has become a key theme of much recent criminal justice legislation and policy aimed at the effective management of high-risk offenders. In this article we draw on two recent research projects to examine the two main approaches to public protection: the community protection model, and the public health approach. Drawing on the recent work of Pat O'Malley we examine the underpinning assumptions of each `risk technology' and how each constructs notions of both offenders and the public in their approach to risk regulation. The article concludes by arguing that each differs significantly in the extent to which they either include or exclude high-risk offenders (particularly sex offenders), and in their expectations of public responsibility for risk management.
Consumer society, commodification and offender management
Authors: McCulloch Trish , McNeill Fergus
Published: July 2007

This article aims to set current developments in `offender management' services in England and Wales and in Scotland within the contexts first of a discussion of Bauman's analysis of crime and punishment in consumer society and second of wider debates about the commodification of public services. Rather than examining the formal commodification of offender management through organizational restructuring, `contestability' and marketization, the authors examine the extent to which the substantive commodification of offender management is already evidenced in the way that probation's products, consumers and processes of production have been reconfigured within the public sector. In the concluding discussion, they consider both some limitations on the extent of commodification to date and the prospects for the containment or moderation of the process in the future.
Coerced drug treatment in the criminal justice system
Authors: Seddon Toby
Published: July 2007

A striking phenomenon in many western countries is the increasing use of the criminal justice system as a means of channelling and coercing drug users into treatment. Despite somewhat equivocal research evidence about its effectiveness, this approach has continued to expand, including in Britain. This article takes a step back and explores some of the critical background issues that have been largely overlooked to date. Some conceptual, ethical and criminological aspects of coerced treatment in the criminal justice system are considered. It is argued that coerced treatment is a central issue for both contemporary criminology and criminal justice policy.
`Too many chiefs and not enough chief executives'
Authors: Button Mark , Williamson Tom , Johnston Les
Published: July 2007

The Private Finance Initiative (PFI) has proved to be one of the most controversial policies of the Labour government. Indeed, despite opposition from core government support groups New Labour has still been keen to promote PFI. In some parts of the public sector this had led to substantial and radical projects being pursued. In the police service, however, there have been relatively few projects and most that have emerged have been relatively conservative, restricted to new buildings with facilities management provision. This article will examine some of the barriers to the expansion of PFI in the police service. Central to this is the structure of the police service with 43 constabularies operating within a tripartite structure of governance. On top of this are cultural issues specific to the police service and to chief constables, combined with other general barriers. The article will also examine the new financial prudential code and illustrate that this may be the `final nail in the coffin' for the PFI in the police service.
A procedure for identifying homologous alternative splicing events
Authors: Talavera David , Hospital Adam , Orozco Modesto , de la Cruz Xavier
Published: July 2007

Background

The study of the functional role of alternative splice isoforms of a gene is a very active area of research in biology. The difficulty of the experimental approach (in particular, in its high-throughput version) leaves ample room for the development of bioinformatics tools that can provide a useful first picture of the problem. Among the possible approaches, one of the simplest is to follow classical protein function annotation protocols and annotate target alternative splice events with the information available from conserved events in other species. However, the application of this protocol requires a procedure capable of recognising such events. Here we present a simple but accurate method developed for this purpose.

Results

We have developed a method for identifying homologous, or equivalent, alternative splicing events, based on the combined use of neural networks and sequence searches. The procedure comprises four steps: (i) BLAST search for homologues of the two isoforms defining the target alternative splicing event; (ii) construction of all possible candidate events; (iii) scoring of the latter with a series of neural networks; and (iv) filtering of the results. When tested in a set of 473 manually annotated pairs of homologous events, our method showed a good performance, with an accuracy of 0.99, a precision of 0.98 and a sensitivity of 0.93. When no candidates were available, the specificity of our method varied between 0.81 and 0.91.

Conclusion

The method described in this article allows the identification of homologous alternative splicing events, with a good success rate, indicating that such method could be used for the development of functional annotation of alternative splice isoforms.
Staffing level: a determinant of late-onset ventilator-associated pneumonia
Authors: Hugonnet Stéphane , Uçkay Ilker , Pittet Didier
Published: July 2007

Introduction

The clinical and economic burden of ventilator-associated pneumonia (VAP) is uncontested. We conducted the present study to determine whether low nurse-to-patient ratio increases the risk for VAP and whether this effect is similar for early-onset and late-onset VAP.

Methods

This prospective, observational, single-centre cohort study was conducted in the medical intensive care unit (ICU) of the University of Geneva Hospitals. All patients who were at risk for ICU-acquired infection admitted from January 1999 to December 2002 were followed from admission to discharge. Collected variables included patient characteristics, admission diagnosis, Acute Physiology and Chronic Health Evaluation II score, co-morbidities, exposure to invasive devices, daily number of patients and nurses on duty, nurse training level and all-site ICU-acquired infections. VAP was diagnosed using standard definitions.

Results

Among 2,470 patients followed during their ICU stay, 262 VAP episodes were diagnosed in 209/936 patients (22.3%) who underwent mechanical ventilation. Median duration of mechanical ventilation was 3 days (interquartile range 2 to 6 days) among patients without VAP and 11 days (6 to 19 days) among patients with VAP. Late-onset VAP accounted for 61% of all episodes. The VAP rate was 37.6 episodes per 1,000 days at risk (95% confidence interval 33.2 to 42.4). The median daily nurse-to-patient ratio over the study period was 1.9 (interquartile range 1.8 to 2.2). By multivariate Cox regression analysis, we found that a high nurse-to-patient ratio was associated with a decreased risk for late-onset VAP (hazard ratio 0.42, 95% confidence interval 0.18 to 0.99), but there was no association with early-onset VAP.

Conclusion

Lower nurse-to-patient ratio is associated with increased risk for late-onset VAP.
A semi-quantitative GeLC-MS analysis of temporal proteome expression in the emerging nosocomial pathogen Ochrobactrum anthropi
Authors: Graham Robert Leslie James , Sharma Mohit K , Ternan Nigel G , Weatherly D Brent , Tarleton Rick L , McMullan Geoff
Published: July 2007

Background

The α-Proteobacteria are capable of interaction with eukaryotic cells, with some members, such as Ochrobactrum anthropi, capable of acting as human pathogens. O. anthropi has been the cause of a growing number of hospital-acquired infections; however, little is known about its growth, physiology and metabolism. We used proteomics to investigate how protein expression of this organism changes with time during growth.

Results

This first gel-based liquid chromatography-mass spectrometry (GeLC-MS) temporal proteomic analysis of O. anthropi led to the positive identification of 131 proteins. These were functionally classified and physiochemically characterized. Utilizing the emPAI protocol to estimate protein abundance, we assigned molar concentrations to all proteins, and thus were able to identify 19 with significant changes in their expression. Pathway reconstruction led to the identification of a variety of central metabolic pathways, including nucleotide biosynthesis, fatty acid anabolism, glycolysis, TCA cycle and amino acid metabolism. In late phase growth we identified a number of gene products under the control of the oxyR regulon, which is induced in response to oxidative stress and whose protein products have been linked with pathogen survival in response to host immunity reactions.

Conclusion

This study identified distinct proteomic profiles associated with specific growth points for O. anthropi, while the use of emPAI allowed semi-quantitative analyses of protein expression. It was possible to reconstruct central metabolic pathways and infer unique functional and adaptive processes associated with specific growth phases, thereby resulting in a deeper understanding of the physiology and metabolism of this emerging pathogenic bacterium.
Differential effects ofFrancisella tularensislipopolysaccharide on B lymphocytes
Authors: Rahhal Riad M , Vanden Bush Tony J , McLendon Molly K , Apicella Michael A , Bishop Gail A
Published: July 2007

Francisella tularensis, a designated Category A biological agent, can cause severe infection in humans. Previous studies have demonstrated a significant immunoprotective role for B lymphocytes in animal models, but the responses of human B lymphocytes to F. tularensis components are largely unknown. The LPS of F. tularensis is atypical and has been reported to lack biological activity on myeloid cells and mouse B cells. Our study characterized the immunological effects of highly purified LPS from different stains of F. tularensis on human B lymphocytes and compared these effects with those on mouse B cells and human monocyte-derived macrophages. Results indicate that marked differences exist between cell type and species in specific responses to this interesting bacterial component. In sharp contrast to responses of mouse splenic B cells or human macrophages, human peripheral B cells showed reproducibly elevated IL-6, TNF-α, and antibody production in response to F. tularensis LPS. Data also indicated that these activated human B lymphocytes may subsequently promote the activation of other immune cell types by direct cell–cell interaction. Further investigation into the potential usefulness of F. tularensis LPS as an adjuvant component of a more optimal subunit vaccine is warranted, as it is now clear that it is not biologically inactive, as assumed previously.
Hematopoiesis from Human Embryonic Stem Cells
Authors: BHATIA MICKIE
Published: July 2007

Abstract:  Human embryonic stem cells (hESCs) have the capacity to differentiate into multiple lineages, such as neural and hepatic, and include the ability to form hematopoietic cells. Efforts to develop efficient methods to induce hematopoietic differentiation effectively from hESCs, and generate primitive blood stem cells with multilineage hematopoietic repopulating function, are ongoing in several laboratories. Here, we will discuss the past and current progress of our laboratory in this area, and share our ideas to further this use of hESCs in both experimental and clinical hematology.
Differential Effects of G Protein–Coupled Receptors on Hematopoietic Progenitor Cell Growth Depend on their Signaling Capacities
Authors: XUE XINGKUI , CAI ZHEN , SEITZ GABRIELE , KANZ LOTHAR , WEISEL KATJA C. , MÖHLE ROBERT
Published: July 2007

Abstract:  We have shown that CD34+ hematopoietic progenitor and stem cells (HPCs) consistently express several G protein–coupled receptors (GPCRs): the chemokine receptor CXCR4, the cysteinyl‐leukotriene receptor cysLT1, and receptors for sphingosine 1‐phosphate (S1P), particularly S1P1. These GPCRs differentially mediate chemotactic, adhesive, and proliferative responses in HPCs. To elucidate the diversity of the responses observed, we compared their signaling capacities in CD34+ cells. In primary CD34+ progenitors, the strongest effects on calcium signaling (intracellular calcium fluxes) were mediated by cysLT1. Analyses in CD34+ cell lines revealed that calcium signaling induced by cysLT1 was only partially inhibited by pertussis toxin (PTX), while responses induced by CXCR4 and S1P receptors were completely blocked. These findings indicate that cysLT1 signals via Gi and Gq proteins, while CXCR4 and also S1P receptors (e.g., S1P1) only induce Gi protein‐mediated effects. By analysis of downstream signaling, we could provide further evidence that combined activation of PTX‐insensitive (Gq‐mediated) and PTX‐sensitive (Gi‐mediated) pathways by cysLT1 may explain the strong and broad effects of cysteinyl‐leukotrienes in early hematopoietic cells, while signaling of CXCR4 and S1P1 solely depends on Gi proteins, resulting in effects mainly restricted to migration and adhesion.
Flt3 in Regulation of Type I Interferon‐Producing Cell and Dendritic Cell Development
Authors: ONAI NOBUYUKI , OBATA‐ONAI AYA , SCHMID MICHAEL A. , MANZ MARKUS G.
Published: July 2007

Abstract:  Flt3‐ligand is a nonredundant cytokine in type I interferon‐producing cell (IPC) and dendritic cell (DC) development. We demonstrated that IPC and DC differentiation potential is confined to Flt3+‐hematopoietic progenitor cells, that Flt3‐ligand drives development along both lymphoid and myeloid developmental pathways from Flt3+‐progenitors to Flt3+‐IPCs and ‐DCs, and that in vivo pharmacologic inhibition of Flt3‐signaling leads to disruption of IPC and DC development in spite of consecutive Flt3‐ligand upregulation in treated animals. We here summarize our recent findings that overexpression of human Flt3 in Flt3− and Flt3+ hematopoietic progenitors rescues and enhances their IPC and DC differentiation potential, respectively. Based on these data, we propose an instructive, demand‐regulated, cytokine‐driven IPC and DC regeneration model, where high Flt3‐ligand levels initiate a self‐sustaining, Flt3‐STAT3 and ‐PU.1‐mediated IPC and DC differentiation program in Flt3+‐hematopoietic progenitor cells.
Cytokine Signaling, Lipid Raft Clustering, and HSC Hibernation
Authors: YAMAZAKI SATOSHI , IWAMA ATSUSHI , MORITA YOHEI , ETO KOJI , EMA HIDEO , NAKAUCHI HIROMITSU
Published: July 2007

Abstract:  Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) niche in a noncycling state and enter the cell cycle at long intervals. This unique property of HSCs is reminiscent of hibernation in mammals. However, little is known about inter‐ and intracellular signaling mechanisms underlying this unique property of HSCs. This is largely due to the paucity of HSCs making application of traditional signal transduction assays difficult. To address these issues, we have developed a novel assay based on in‐droplet single‐cell staining and quantitative fluorescence imaging analysis. Using this assay system, we demonstrate that freshly isolated HSCs from the BM niche lack lipid raft clustering, exhibit repression of the AKT‐FOXO signaling pathway, and express abundant p57Kip2 cyclin‐dependent kinase inhibitor. Lipid raft clustering induced by cytokines was essential for HSC re‐entry into the cell cycle. Conversely, inhibition of lipid raft clustering caused sustained nuclear accumulation of FOXO transcription factors and induced HSC hibernation ex vivo. Among niche signals examined, transforming growth factor‐β (TGF‐β) efficiently inhibited lipid raft clustering and induced p57Kip2 expression, leading to HSC hibernation. These data uncover a critical role for lipid rafts in HSC fate decision and establish the role of TGF‐β as a niche signal in control of HSC hibernation in the BM niche.
Inference, Validation, and Dynamic Modeling of Transcription Networks in Multipotent Hematopoietic Cells
Authors: SONEJI SHAMIT , HUANG SUI , LOOSE MATTHEW , DONALDSON IAN JOHN , PATIENT ROGER , GÖTTGENS BERTHOLD , ENVER TARIQ , MAY GILLIAN
Published: July 2007

Abstract: Identifying the transcription factor interactions that are responsible for cell‐specific gene expression programs is key to understanding the regulation of cell behaviors, such as self‐renewal, proliferation, differentiation, and death. The rapidly increasing availability of microarray‐derived global gene expression data sets, coupled with genome sequence information from multiple species, has driven the development of computational methods to reverse engineer and dynamically model genetic regulatory networks. An understanding of the architecture and behavior of transcriptional networks should lend insight into how the huge number of potential gene expression programs is constrained and facilitates efforts to direct or redirect cell fate.
NUP98 Dysregulation in Myeloid Leukemogenesis
Authors: MOORE M. A. S. , CHUNG K. Y. , PLASILOVA M. , SCHURINGA J. J. , SHIEH J.‐H. , ZHOU P. , MORRONE G.
Published: July 2007

Abstract:  Nucleoporin 98 (NUP98) is a component of the nuclear pore complex that facilitates mRNA export from the nucleus. It is mapped to 11p15.5 and is fused to a number of distinct partners, including nine members of the homeobox family as a consequence of leukemia‐associated chromosomal translocations. NUP98‐HOXA9 is associated with the t(7;11)(p15;p15) translocation in acute myeloid leukemia (AML), myelodysplastic syndrome, and blastic crisis of chronic myeloid leukemia. Expression of NUP98‐HOXA9 in murine bone marrow resulted in a myeloproliferative disease progressing to AML by 7–8 months. Transduction of NUP98 fusion genes into human CD34+ cells confers a proliferative advantage in long‐term cytokine‐stimulated and stromal cocultures and in NOD‐SCID engrafted mice, associated with a five‐ to eight‐fold increase in hematopoietic stem cells. NUP98‐HOXA9 expression inhibited erythroid and myeloid differentiation but enhanced serial progenitor replating. NUP98‐HOXA9 upregulated a number of homeobox genes of the A and B cluster as well as MEIS1 and Pim‐1, and downmodulated globin genes and C/EBPα. The HOXA9 component of the NUP98‐HOXA9 fusion protein was protected from cullin‐4A–mediated ubiquitination and subsequent proteasome‐dependent degradation. In NUP98‐HOX–transduced CD34+ cells and cells from AML patients with t(7;11)(p15;p15) NUP98 was no longer associated with the nuclear pore complex but formed intranuclear aggregation bodies. Analysis of NUP98 allelic expression in AML and myelodysplastic syndrome showed loss of heterozygosity observed in 29% of the former and 8% of the latter. This was associated with poor prognosis.
Biological and Molecular Evidence for Existence of Lymphoid‐Primed Multipotent Progenitors
Authors: LUC SIDINH , BUZA‐VIDAS NATALIJA , JACOBSEN STEN EIRIK W.
Published: July 2007

Abstract:  Studies from our and other laboratories have over the last 2 years implicated the existence of multipotent progenitors (MPPs) with combined granulocyte–macrophage, B cell, and T cell potential, but little or no megakaryocyte–erythroid (MkE) potential in the adult bone marrow Lineage−SCA‐1+KIT+ (LSK) compartment of multipotent stem and progenitor cells. The evidence for the existence of LSKCD34+FLT3hi lymphoid‐primed MPPs (LMPPs) implicates that a strict separation into common myeloid and lymphoid pathways might not be the first lineage commitment step of hematopoietic stem cells (HSCs). Together with the evidence for existence of common myeloid and common lymphoid progenitors (CMPs and CLPs, respectively), the identification of LMPPs also suggests that at least the granulocyte–macrophage lineage can be generated through alternative pathways. However, the existence of LMPPs has recently been questioned, as there is evidence that at least a fraction of LSKCD34+FLT3hi cells sustains MkE potential. Thus, in more recent studies we have in more detail compared the molecular signature of adult LMPPs to populations of LSK cells enriched for cells with pluripotent HSC activity. Notably, we have found at the global as well as single‐cell level that LMPPs when compared with pluripotent HSCs downregulate the transcriptional priming of genes typically expressed in cells of the MkE lineage, while upregulating early lymphoid genes. Although other studies have suggested that the earliest HSC commitment steps might differ in fetal and adult hematopoiesis, we have also obtained evidence suggesting that the LMPP is defined already during fetal development.
Modulation of Immune Responses by Mesenchymal Stem Cells
Authors: FIBBE WILLEM E. , NAUTA ALMA J. , ROELOFS HELENE
Published: July 2007

Abstract:  Mesenchymal stem cells (MSCs) are multipotent progenitor cells and interest in MSC therapy has been raised by the observation that MSCs are able to modulate immune responses in vitro and in vivo. Here, we show that MSCs are not intrinsically immune privileged and are capable of inducing memory T cell responses following injection in vivo in immunocompetent hosts. After cotransplantation in recipients that have received sublethal irradiation, allogeneic MSCs can still induce an alloresponse that may result in graft rejection, suggesting that the immunogenicity of allogeneic MSCs are not fully prevented by a nonmyeloablative conditioning regimen. It is still unclear whether the immunogenicity of allogeneic MSCs is also preserved following a fully myeloablative conditioning regimen.
Dual role of Mpl receptor during the establishment of definitive hematopoiesis
Authors: Petit-Cocault Laurence , Volle-Challier Cécile , Fleury Maud , Péault Bruno , Souyri Michèle
Published: July 2007

Cytokine signaling pathways are important in promoting hematopoietic stem cell (HSC) self-renewal, proliferation and differentiation. Mpl receptor and its ligand, TPO, have been shown to play an essential role in the early steps of adult hematopoiesis. We previously demonstrated that the cytoplasmic domain of Mpl promotes hematopoietic commitment of embryonic stem cells in vitro, and postulated that Mpl could be important in the establishment of definitive hematopoiesis. To answer this question, we investigated the temporal expression of Mpl during mouse development by in situ hybridization. We found Mpl expression in the HSCs clusters emerging in the AGM region, and in the fetal liver (FL) as early as E10.5. Using Mpl-/- mice, the functional relevance of Mplexpression was tested by comparing the hematopoietic progenitor (HP) content,long-term hematopoietic reconstitution (LTR) abilities and HSC content of control and Mpl-/- embryos at different times of development. In the AGM, we observed delayed production of HSCs endowed with normal LTR but presenting a self-renewal defect. During FL development, we detected a decrease in HP and HSC potential associated with a defect in amplification and self-renewal/survival of the lin-AA4.1+ Sca1+ population of HSCs. These results underline the dual role of Mpl in the generation and expansion of HSCs during establishment of definitive hematopoiesis.
Heart of farce: Almodvar's comic complexities
Authors: Medhurst Andy
Published: July 2007

This article explores the use of comedy in the films of Pedro Almodvar, and argues that his commitment to comic sequences and sensibilities throughout his work causes several complications in how he has been culturally placed and understood. Three themes are considered. First, although
he has been marketed and analysed as a contemporary inheritor of the traditions of European art cinema, his use of comedy sits uneasily with those traditions' commitment to discourses of seriousness and solemnity. Second, his adoption by the primarily Anglo-American queer academy often involves
a neglect of the specifically Spanish context of his work and the role of humour within it. Third, his refusal to jettison comedy from the complex emotional range of his narratives lends his films a richness that disregards conventional genre boundaries and cultural hierarchies in their insistence
that comedic representation and thematic depth are perfectly compatible.
Re-reading Michael Haneke's La Pianiste: schizo-politics and the critique of consumer culture
Authors: Thakur Gautam Basu
Published: July 2007

The paper argues that Michael Haneke's La Pianiste/The Piano Teacher (2001) has not departed from the critique of consumerist culture that his Austrian films represent, neither has Haneke devolved into individualist melodrama following his relocation to France, as some critics have asserted: rather, the film continues Haneke's critique of modern consumerist culture. Focusing on Haneke's characterisation of a psychologically disturbed piano teacher and the narrative construction of the film, this article argues that La Pianiste as a film is geared towards rupturing audience-screen identification with the aim of deconstructing subject positions in consumerist societies. And it is this deliberate rupturing that establishes a connection between Haneke's Austrian films his famous glaciation theory and critique of consumerism and La Pianiste.
Analysis of TATA-binding protein 2 (TBP2) and TBP expression suggests different roles for the two proteins in regulation of gene expression during oogenesis and early mouse development
Authors: Gazdag Emese , Rajkovic Aleksandar , Torres-Padilla Maria Elena , Tora Làszlò
Published: July 2007

Gametogenesis, the process during which germ cells are generated is essential for reproduction. In mammals, maternal mRNA and proteins present in the oocyte are required to ensure the progression of development until the embryo activates its genome after fertilisation. It is well established that the oocyte synthesises these maternal factors during oocyte growth and then undergoes a quiescent transcriptional period that will be resumed only after fertilisation. However, the mechanisms that govern transcriptional regulation and subsequent silencing during oogenesis are not well understood. Here, we have examined the expression and localisation of the TATA-binding protein (TBP) and the related protein TBP2 (also called TRF3, TBP-related factor 3) during oogenesis and in early mouse embryos. We show that TBP is expressed in the oocytes at the beginning of folliculogenesis, but it is undetectable during further stages of oocyte development, and becomes abundant again only after fertilisation. In contrast to TBP, we found that TBP2 is highly expressed in growing oocytes during folliculogenesis, declines upon ovulation, and is almost undetectable after fertilisation by the two-cell stage. The mirroring localisation profile of TBP and TBP2 suggests different roles for the two proteins in establishing specialised programs of gene expression during oocyte development and in early mouse embryos. Analysis of mutant mouse ovaries in which oocyte-specific factors have been knocked-out suggests that TBP2 is a potential candidate for regulating transcriptional control of oogenesis. Moreover, our results obtained with oocytes lacking the oocyte-specific nuclear chaperone nucleoplasmin 2 suggest that TBP2 function may be related to non-condensed chromatin conformation.
AKR1B7 (mouse vas deferens protein) is dispensable for mouse development and reproductive success
Authors: Baumann C , Davies B , Peters M , Kaufmann-Reiche U , Lessl M , Theuring F
Published: July 2007

AKR1B7 (aldo–keto reductase family 1, member 7; also known as mouse vas deferens protein) is a member of the AKR superfamily, and has been suggested to play a role in detoxifying processes on account of its preferred substrates, 4-hydroxynonenal and isocaproaldehyde. High levels of protein expression were found in the vas deferens and the adrenal gland, where sustained expression is dependent on androgen or ACTH respectively. Recently, a remarkable induction of AKR1B7 expression has been reported in the ovary following exogenous injections of LH. In the present study, we confirm this regulation physiologically during the estrous cycle, observing Akr1b7 expression to be restricted to the theca and stromal cells of the proestrus ovary. To further investigate the role of this detoxifying enzyme in both male and female reproduction, we generated knockout mice deficient in AKR1B7. Although AKR1B7 expression in the vas deferens is considerable and tightly regulated in the ovary of wild-type animals, homozygous mutant animals were found to be viable and no reproductive phenotype was observed. Ovarian follicle maturation and spermatozoa parameters remained normal in the absence of this protein. The determination of serum progesterone revealed an increase in hormone concentration in metestrus, while progesterone was found to be decreased in the estrus phase of the cycle in knockout females.
A microarray analysis for genes regulated by interferon-τ in ovine luminal epithelial cells
Authors: Chen Yizhen , Antoniou Eric , Liu Zhilin , Hearne Leonard B , Roberts R Michael
Published: July 2007

Interferon-τ (IFNT) is released by preimplantation conceptuses of ruminant species and prepares the mother for pregnancy. Although one important function is to protect the corpus luteum from the luteolytic activity of prostaglandin-F 2α, IFNT most likely regulates a range of other physiological processes in endometrium. Here, an immortalized cell line from ovine uterine luminal epithelial cells was treated with IFNT for either 8 or 24 h. RNA was subjected to cDNA microarray analysis, with RNA from untreated cells as the reference standard. Of 15 634 genes, 1274 (8%) were IFNT responsive at P<0.01 and 585 at P<0.001 to at least one treatment. Of the latter, 356 were up-regulated and 229 down-regulated. Increasing IFNT concentrations from 10 ng/ml to 10 μg/ml had minor effects, and most genes up- or down-regulated at 8 h were regulated similarly at 24 h. Although IFNT influences many genes implicated in antiviral activity and apoptosis, its action also likely regulates prostaglandin metabolism, growth factors and their receptors, apoptosis and the nuclear factor (NF)-κB cascade, extracellular matrix accretion, angiogenesis, blood coagulation, and inflammation. In particular, it increased mRNA concentrations of genes related to the vascular endothelial growth factor R2 pathway of angiogenesis and down-regulated ones associated with hypoxia. Two genes implicated in the antiluteolytic actions of IFNT (encoding cyclooxygenase-2 and the oxytocin receptor respectively) were down-regulated in response to all treatments. IFNT targets a complex range of physiological processes during the establishment of pregnancy.
Phosphoinositide 3-kinases as a common platform for multi-hormone signaling
Authors: Hirsch Emilio , Costa Carlotta , Ciraolo Elisa
Published: July 2007

In multicellular organisms, concerted actions of different tissues are regulated inside single cells by signal transduction mechanisms that, subsequently to hormones sensing, trigger intracellular responses. In recent years, increasing evidence indicates phosphoinositide 3-kinases (PI3K) as crucial signal transducing elements that regulate communication across the plasma membrane. PI3K generate lipid secondary messengers that trigger a plethora of intracellular responses ranging from metabolic regulation to cell proliferation, survival, and migration. The growing number of hormones that relay signals by activating PI3K suggests not only multiple roles of these enzymes in the regulation of different physiological responses but also a way by which common reactions can be stimulated by different inputs. This review will thus focus on the different pathways that converge on PI3K activation, with particular attention to the paradigmatic PI3K involvement in insulin signaling.
Maternal betamethasone administration reduces binucleate cell number and placental lactogen in sheep
Authors: Braun Thorsten , Li Shaofu , Moss Timothy J M , Newnham John P , Challis John R G , Gluckman Peter D , Sloboda Deborah M
Published: July 2007

The placenta may mediate glucocorticoid-induced fetal growth restriction. Previous studies have examined effects of fetal cortisol in sheep, which reduces placental binucleate cell (BNC) number; the source of ovine placental lactogen (oPL). The effects of maternal GC are unknown. Therefore, this study examined the effects of maternal betamethasone (BET) administration on BNC number, distribution, placental oPL protein levels, and maternal and fetal plasma oPL levels. Pregnant ewes were randomized to receive injections of saline or one (104 days of gestation; dG), two (104 and 111 dG), or three (104, 111, and 118 dG) doses of BET (0.5 mg/kg). Placental tissue was collected before, during, and after the period of BET treatment. Fetal (121–146 dG) and placental (121 dG) weights were decreased after BET when compared with controls. In controls, the mean number of BNCs increased until 132 dG and decreased thereafter. Placental oPL protein levels peaked at 109 dG and remained stable thereafter. Maternal plasma oPL levels in controls increased across gestation; fetal plasma oPL levels decreased. BNCs were reduced by 24% to 47% after BET when compared with controls at all ages studied. Placental oPL protein levels, maternal, and fetal plasma oPL levels were also reduced after BET injections, but recovered to values that were not different to controls near term. BET disrupted the normal distribution of BNCs within the placentome. These data may suggest a placental role in growth restrictive effects of prenatal maternal BET exposure through alterations in placental output of oPL, a key metabolic hormone of pregnancy.