bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Frequencies and Mode Shapes of Timoshenko Beams with Attachments
Authors: Magrab Edward B.
Published: July 2007

The Laplace transform is used to obtain a solution for a Timoshenko beam on an elastic foundation with several combinations of discrete in-span attachments and with several combinations of attachments at the boundaries. These attachments include translation and torsion springs, masses, and undamped single degree-of-freedom systems. The Laplace transform technique, which apparently has not been used previously to solve for the eigenvalues of coupled systems of equations, produces a solution in which the boundary conditions can be considered independently of the number and type of in-span attachments. Taking advantage of this independence, many specific combinations of in-span attachments and boundary attachments are examined. It is shown that the Laplace transform method removes some of the drawbacks of the most frequently used methods used to solve Timoshenko beams with in-span attachments: beam partitioning, Green's functions, and Lagrange multipliers. Excellent agreement is found upon comparing previously reported results for a wide range of boundary conditions and attachments. In addition, several sets of new results are given.
Gear Surface Roughness Induced Noise Prediction Based on a Linear Time-varying Model with Sliding Friction
Authors: Kim Seungbo , Singh Rajendra
Published: July 2007

This article presents a new gear surface roughness induced noise source model while taking into account the sliding contacts between meshing gear teeth. The surface asperities on tooth surfaces are modeled as compact structural beam elements that radiate sound in the off-line of action after sliding impacts, against asperities of the meshing surface, occur. A linear time-varying (LTV) model of a spur gear pair (with sliding friction) is employed to calculate the instantaneous sliding velocity between pinion and gear teeth, which is then applied to the asperities as the initial condition. The transient sound field from the flexural motions of surface asperities (acoustically baffled along their axes), which are released from the cylindrical Hertzian contact zone in gear teeth, is computed. The modal superposition method is used for far and free field calculations given the surface roughness and its (assumed) asperity distribution on the tooth profile. Typical sound pressure predictions show that the noise levels increase with operating speeds and surface roughness.
Transition of Membrane/Bending Neural Signals on Transforming Adaptive Shells
Authors: Dehaven J.G. , Han Y. , Tzou H.S.
Published: July 2007

Sensing and control are essential to achieving the high precision and high performance of modern aerospace structures and systems. The objective of this study is (1) to investigate spatial microscopic neural signal generations and variations from infinitesimal piezoelectric neurons over a transforming cylindrical shell panel at various curvature angles, and (2) to determine dominating signal components resulting from longitudinal/circumferential membrane strains and/or longitudinal/circumferential bending strains at various shell modes. Dynamic equations of cylindrical shells are defined first, followed by free-vibration analysis. Then, mode shape functions and modal spatial strain distributions are used to determine the signal generation of distributed neuron sensors laminated on a linear cylindrical shell panel. To demonstrate signal variations on transforming shells, the microscopic signal generations of infinitesimal piezoelectric sensors or neurons are investigated for three selected discrete curvature angles, i.e. β* = 30°, 90°, and 150°, ofa simply-supported cylindrical shell panel. Evaluating these three cases suggests that (1) the bending induced signal dominates for most modes of shallow shells and (2) the membrane induced signal dominates for lower modes and yields to the bending signal at higher natural modes of deep shells. The shell curvature is the key factor determining this transition from bending dominated behavior to membrane dominated behavior while the curvature increases from 0° to 360°. Once the dominating signal component(s) is identified, one can further select appropriate actuators to effectively counteract and to control specific modes or shapes of shell structures.
Regular Paper: A Study of Architectural Optimization Methods in Bioinformatics Applications
Authors: Tan G. , Xu L. , Dai Z. , Feng S. , Sun N.
Published: July 2007

Studies in the optimization of sequence alignment have been carried out in bioinformatics. In this paper, we have focused on two aspects: memory usage and execution time. Our study suggests that cache memory does not have a significant effect on system performance. Our attention then turns to optimize Smith—Waterman's algorithm. Two instruction level methods have been proposed and 2—8 fold speed improvements have been observed after the optimization has been implemented. Further improvements on system performance have been achieved by overlapping computation with system I/O usage.
Long-term effects of noticing on oral output
Authors: Mennim Paul
Published: July 2007

This paper reports on the effects of classroom exercises that encourage noticing and conscious attention to form, which were part of a university EFL oral presentation course in Japan. The students on the course were given a set of exercises that encouraged them to notice and to reflect on L2 forms of their own choosing throughout one academic year. Records of their noticing were tracked throughout the year and recordings of their oral output made over the same period were analysed to determine whether there was any development in the use of the forms that the students had noticed. The paper describes an initial analysis of the tracking of two students' noticing and subsequent use of a non-count noun, which presented them with difficulties at the start of the year. Nine months later their accuracy in the use of this word was much improved. The paper considers how the students' noticing of the word might have related to this improvement.
The ZPD and whole class teaching: Teacher-led and student-led interactional mediation of tasks
Authors: Guk Iju , Kellogg David
Published: July 2007

Vygotsky's `zone of proximal development (ZPD)' has become associated with the individual `scaffolding' of learners. As a result, because teachers need to teach the whole class, many public school teachers have had to dismiss the concept as unworkable. Yet Vygotsky himself was chiefly concerned with public school teaching and firmly rejected the idea of a `pedagogical duet' between learner and teacher. He also dismissed the teacher who attempted to provide the ensemble of learning content by him or herself as a `rickshaw puller', arguing instead that a teacher should be a `tram driver', who organizes the social environment of learning. One way in which the teacher might do this is by mediating a learning task for a single learner or a group of learners, who then mediate the task for their classmates in group-work. We present evidence that in this situation the way in which learners mediate tasks differs from the way in which teachers do, and argue that this suggests learner-to-learner mediation is in important ways closer to what Vygotsky termed `internalization'. We believe that T-S and S-S interactional mediation do not create two different ZPDs but may instead lie within a single, whole class ZPD.
A preliminary study of pre-service teachers as readers in Singapore: Prolific, functional, or detached?
Authors: Cox Robyn , Schaetzel Kirsten
Published: July 2007

This paper describes a research study completed in Singapore with students enrolled in an education degree program. The researchers were interested in the reading habits of Singaporean students who will become teachers of English in the Singapore government teaching service. Of interest is the data collection method which involved the development of characters of young adult readers of English in Singapore following work by Marshall (2000). Students selected the character most similar to themselves from three different descriptive characters of readers. They then highlighted salient features in the character that led them to select this character and also highlighted those features that were not similar to them. This innovative approach to data collection was used to reveal the characteristics of student readers and then consider the resultant English teachers that these readers might become. Possible changes to teacher training programs are discussed.
A comparison of the effects of image-schema-based instruction and translation-based instruction on the acquisition of L2 polysemous words
Authors: Morimoto Shun , Loewen Shawn
Published: July 2007

This quasi-experimental study investigated the effectiveness of two types of vocabulary instruction — image-schema-based instruction (ISBI) and translation-based instruction (TBI) — on the acquisition of second language (L2) polysemous words. Fifty-eight Japanese high school learners of English were divided into two treatment groups (ISBI and TBI) and a control group. The treatment groups were given 20 minutes of instruction on the target words, namely the verb break and the preposition over. In order to examine the effectiveness of instruction, an acceptability judgment test and a production test were administered prior to instruction (pre-test), two days after instruction (post-test 1) and two weeks after instruction (post-test 2). The results showed that ISBI tended to be as effective as TBI for both acceptability judgment test and production test scores, except in one case where ISBI was significantly more effective than TBI. This study suggests that image-schema from the field of cognitive semantics can serve as a pedagogical devise in teaching L2 polysemous words.
TV news and political change in Brazil
Authors: Porto Mauro
Published: July 2007

The article analyzes the changes that since the mid-1990s have transformed journalistic practices in Brazil's most powerful media institution. More especially, the aim is to investigate the transformation of TV Globo's News Division and situate this process in relation to the democratization of Brazilian politics and society. Based on content analysis of Jornal Nacional, TV Globo's main newscast, and on in-depth interviews with four senior journalists of the network, the article stresses how the new conditions brought by political and social democratization help explain these changes. In particular, the deepening of democracy in Brazil created new constraints that forced TV Globo to overcome a tradition of more explicit political biases and to minimize the initial trend toward tabloidization with an increase of hard news coverage.
Creating a new(s) view of the environment
Authors: Matthews Julian
Published: July 2007

Based on a production study of children's news, this article examines the unique new(s) views of the environment created by news programming. Children's news programmes, such as the BBC's programme Newsround, construct a new(s) view of environmental degradation. Studying the children's news programme thus provides insights into the unexplored relationship between news differentiation and environmental news representations. This particular investigation explores and demonstrates how Newsround and its informing conception of its child audience produces a simplified and personalized view of the environment, which powerfully undermines a reasoned understanding of the relationship between human beings and the natural world. By this means it examines the important connections between news conventions, news programmes and new(s) views of the environment.
Devolution and Neoliberalism in the Canadian Welfare State
Authors: Mcbride Stephen , Mcnutt Kathleen
Published: July 2007

The Canadian welfare state has changed significantly in the last decade with the federal devolution of policy responsibilities creating opportunities for some provinces to adopt American social policy ideas. Given the expectations of resilience and non-convergence, in the welfare state literature, this article addresses the issues of policy change by demonstrating that the movement of British Columbia's labour and social policy towards international neoliberal norms, including policy examples set in many US jurisdictions, have produced limited convergence. We suggest that this indicates that more change has occurred and is occurring in the Canadian welfare state than the resilience model or comparative public policy literature would indicate.
`What a wonderful world!': On the `touristic ways of seeing', the knowledge and the politics of the `culture industries of otherness'
Authors: Favero Paolo
Published: July 2007

Focusing on three ethnographic events (an Italian charter tour to Pakistan, a shopping event in a village replica in New Delhi and a festival of culture and travel in Italy) this article looks into the contemporary `culture industries of otherness' that is, those commercial events promoting knowledge about the world in its diversity. Criss-crossing visual anthropology, tourism anthropology and scholarly work on the politics of multi-culturalism the article will introduce the notion of the `touristic ways of seeing'. As modalities for contemplating cultural difference in the contemporary globalized habitats of the world such ways of seeing are connected to wider representational practices linked to the consumption of films, television and advertisement. Through their `form', they present us a world knowable by seeing and enjoying it. Yet, as I will discuss at the end of the article, this knowledge hides questions of production, power and politics and thus appears counterproductive to the creation of dialogue across cultural borders.
Stalking the cannibals
Authors: Palmer Catherine , Lester Jo-Anne
Published: July 2007

Outwardly Dennis O'Rourke's film, Cannibal Tours, is just another travel documentary, but to categorize it thus is to misunderstand its significance. `Straight' readings of the film present it as an example of the negative impacts of tourism or as a commentary on touristic encounters with the exotic. We part company from such readings because they largely ignore the filmmaker's art, the role of O'Rourke in constructing the film's narrative. O'Rourke employs the ubiquitous camera to present his critique of a western mindset that continues to be fascinated by the primitive Other. Our discussion focuses on both the filmmaker's art and the lure of the primitive as an oneiric exercise for western tourists. Specifically, we explore the role of the camera in constructing the relationship between modernity and the pre-modern Other. Overall, then, this discussion represents a journey through the mind of O'Rourke, a journey into his framing of tourism.
Embodying imperial spectacle: dressing Lady Curzon, Vicereine of India 1899—1905
Authors: Thomas Nicola J.
Published: July 2007

This article contributes an embodied historical cultural geography that pays attention to the interplay between the dressed body, material culture and textual representation. Debates concerning the politics of identity, performance and subjectivity, transnational circuits of consumption, clothing as material culture, and the place of dress and colonial power, are drawn on to configure a material and embodied biography of the clothes and the clothing of Lady Curzon, Vicereine of India 1898—1905. The geographies of exchange, appropriation, transculturation and hybridity that are woven into her clothing practices are examined in relation to discussions of the regulation and performance of colonial power and authority. This article pays close attention to the material culture approach to the `lived garment', examining cloth and associated wearing practices in the broader context of cultures of consumption. In so doing it charts the intimate historical cultural geographies of modernity and colonial power.
What's wrong with globalization?
Authors: Sparks Colin
Published: July 2007

This article reviews the range of views that are grouped together under the heading `theories of globalization'. Rather than advocating one from the range of conflicting theories, the article attempts to establish the basic ideas that they have in common. These, mostly very abstract, ideas are then developed in order to arrive at propositions that may be examined in relation to evidence about the contemporary world. It is found that none of the five major planks upon which most theories of globalization rest are accurate. On the contrary, even quite easily available evidence contradicts them. It is therefore concluded that, whatever their popular appeal, theories of globalization are not an accurate guide to the investigation of the world. The distorted consequences that flow from an adherence to a mistaken theory are demonstrated through a consideration of the nature of contemporary migration, which is shown to be an overwhelmingly intra-state, rather than transnational, phenomenon. It is argued that processes like this, and the other developments considered here, are better explained by developing the same kinds of analytic tools that were appropriate to an earlier phase of capitalist development.
Concentration of ownership, the fall of unions and government legislation in Turkey
Authors: Christensen Christian
Published: July 2007

As a subject of academic research, Turkey has found itself caught in an intellectual and theoretical `no-man's land' located somewhere between south-eastern Europe and the Middle East. This article aims to position the Turkish media experience in relation to those of geographically, politically, economically and historically proximate nations/regions. It analyses the problems facing journalists and the institutions of journalism in Turkey by addressing three interrelated phenomena: (1) the concentration of media ownership in Turkey; (2) the efforts (largely successful) on the part of media owners to break the power of unions; and (3) government legislation affecting the rights and working environments of news workers. Following a presentation of empirical data on these three areas, I offer suggestions as to how the present situation in Turkey could open the door for the further refinement of research on, and theory regarding, nationally and regionally specific media.
Borderline sentencing
Authors: Millie Andrew , Tombs Jacqueline , Hough Mike
Published: July 2007

This article draws together findings from two related studies of sentencing in England and Wales, and Scotland. It examines how sentencers in the two jurisdictions differ in their sentencing decision making, with a focus on cases on the borderline between prison and a community penalty. The article suggests that, despite differences in legal systems and criminal justice structures, sentencers' decision making in the two jurisdictions was remarkably similar. In both jurisdictions they took account of a wide range of factors in reaching their decisions, among which the legal category of the offence under sentence was often subsidiary to other considerations. The main difference between the two jurisdictions was the much more dramatic rate of increase in the adult prison population in England and Wales than in Scotland. Several possible explanations are offered for this, including the literal and metaphorical distance of Scotland from Westminster and the greater impact of sentencing guidance south of the border—which has probably had a largely unintended inflationary effect on the prison population.
Decreased expression of tumor necrosis factor family receptors involved in humoral immune responses in preterm neonates
Authors: Kaur Kulwant , Chowdhury Shimul , Greenspan Neil S. , Schreiber John R.
Published: July 2007

Neonates have an increased rate of infection with encapsulated bacteria compared with older children and adults because of diminished antibody responses to T-independent (TI) antigens such as bacterial polysaccharides. Because the interactions of tumor necrosis factor (TNF) family ligands BAFF and APRIL with the TNF family receptors (TNFRs) TACI, BCMA, and BAFF-R are crucial to TI antibody responses, we measured the expression of these receptors on adult and cord blood–derived term and preterm neonatal B cells. Preterm neonatal B cells expressed less TACI, BCMA, and BAFF-R compared with adult B cells and had significantly less proliferation compared with adult B cells after stimulation with human recombinant BAFF and anti-IgM in an assay in which TACI-Fc fusion protein inhibits B-cell proliferation. In addition, neonatal dendritic cells had diminished expression of B7–1, B7–2, and CD40 compared with adult cells. Finally, neonatal B cells, particularly preterm B cells, exhibited markedly decreased production of IgG and IgA in response to CD40L and IL-10. Overall, this study shows that maturational delay in TNFR expression particularly by preterm neonatal B cells may interfere with effective antibody responses to TI antigens, cognate T- and B-cell interactions and normal isotype switching.
Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes
Authors: Mohamedali Azim , Gäken Joop , Twine Natalie A. , Ingram Wendy , Westwood Nigel , Lea Nicholas C. , Hayden Janet , Donaldson Nora , Aul Carlo , Gattermann Norbert , Giagounidis Aristotle , Germing Ulrich , List Alan F. , Mufti Ghulam J.
Published: July 2007

Low-risk myelodysplastic syndrome (MDS) with normal cytogenetics accounts for approximately 50% of MDS patients. There are no pathognomonic markers in these cases and the diagnosis rests on cytomorphologic abnormalities in bone marrow and/or peripheral blood. Affymetrix high-resolution single-nucleotide polymorphism (SNP) genotyping microarrays allow detection of cytogenetically cryptic genomic aberrations. We have studied 119 low-risk MDS patients (refractory anemia [RA] = 22; refractory cytopenia with multilineage dysplasia [RCMD] = 51; refractory anemia with ringed sideroblasts [RARS] = 12; refractory cytopenia with multilineage dysplasia with ringed sideroblasts [RCMD-RS] = 12; 5q− syndrome = 16; refractory anemia with excess blasts [RAEB] = 6) using SNP microarrays to seek chromosomal markers undetected by conventional cytogenetics. Loss of heterozygosity (LOH) detected by 50K arrays was verified using 250K and 500K arrays. We demonstrate the presence of uniparental disomy (UPD) in 46%, deletions in 10%, and amplifications in 8% of cases. Copy number (CN) changes were acquired, whereas UPDs were also detected in constitutional DNA. UPD on 4q was identified in 25% of RARS, 12% of RCMD with normal cytogenetics, 17% of RAEB, and 6% of 5q− syndrome cases. Univariate analysis showed deletions (P = .04) and International Prognostic Scoring System (IPSS; P < .001) scores correlated with overall survival; however, on multivariate analysis only IPSS scores retained prognostic significance (P < .001). We show, for the first time, that SNP microarray analysis in low-risk MDS patients reveals hitherto unrecognized UPD and CN changes that may allow stratification of these patients for early therapeutic interventions.
Ancestral European roots of Helicobacter pylori in India
Authors: Devi S Manjulata , Ahmed Irshad , Francalacci Paolo , Hussain M Abid , Akhter Yusuf , Alvi Ayesha , Sechi Leonardo A , Mégraud Francis , Ahmed Niyaz
Published: July 2007

Background

The human gastric pathogen Helicobacter pylori is co-evolved with its host and therefore, origins and expansion of multiple populations and sub populations of H. pylori mirror ancient human migrations. Ancestral origins of H. pylori in the vast Indian subcontinent are debatable. It is not clear how different waves of human migrations in South Asia shaped the population structure of H. pylori. We tried to address these issues through mapping genetic origins of present day H. pylori in India and their genomic comparison with hundreds of isolates from different geographic regions.

Results

We attempted to dissect genetic identity of strains by multilocus sequence typing (MLST) of the 7 housekeeping genes (atp A, efp, ure I, ppa, mut Y, trp C, yph C) and phylogeographic analysis of haplotypes using MEGA and NETWORK software while incorporating DNA sequences and genotyping data of whole cag pathogenicity-islands (cag PAI). The distribution of cag PAI genes within these strains was analyzed by using PCR and the geographic type of cag A phosphorylation motif EPIYA was determined by gene sequencing. All the isolates analyzed revealed European ancestry and belonged to H. pylori sub-population, hpEurope. The cag PAI harbored by Indian strains revealed European features upon PCR based analysis and whole PAI sequencing.

Conclusion

These observations suggest that H. pylori strains in India share ancestral origins with their European counterparts. Further, non-existence of other sub-populations such as hpAfrica and hpEastAsia, at least in our collection of isolates, suggest that the hpEurope strains enjoyed a special fitness advantage in Indian stomachs to out-compete any endogenous strains. These results also might support hypotheses related to gene flow in India through Indo-Aryans and arrival of Neolithic practices and languages from the Fertile Crescent.
Prevalence, awareness and control of diabetes in the Seychelles and relationship with excess body weight
Authors: Faeh David , William Julita , Tappy Luc , Ravussin Eric , Bovet Pascal
Published: July 2007

Background

The evidence for a "diabesity" epidemic is accumulating worldwide but population-based data are still scarce in the African region. We assessed the prevalence, awareness and control of diabetes (DM) in the Seychelles, a rapidly developing country in the African region. We also examined the relationship between body mass index, fasting serum insulin and DM.

Methods

Examination survey in a sample representative of the entire population aged 25–64 of the Seychelles, attended by 1255 persons (participation rate of 80.2%). An oral glucose tolerance test (OGTT) was performed in individuals with fasting blood glucose between 5.6 and 6.9 mmol/l. Diabetes mellitus (DM), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined along criteria of the ADA. Prevalence estimates were standardized for age.

Results

The prevalence of DM was 11.5% and 54% of persons with DM were aware of having DM. Less than a quarter of all diabetic persons under treatment were well controlled for glycemia (HbA1c), blood pressure or LDL-cholesterol. The prevalence of IGT and IFG were respectively 10.4% and 24.2%. The prevalence of excess weight (BMI ≥ 25 kg/m2) and obesity (BMI ≥ 30 kg/m2) was respectively 60.1% and 25.0%. Half of all DM cases in the population could be attributed to excess weight.

Conclusion

We found a high prevalence of DM and pre-diabetes in a rapidly developing country in the African region. The strong association between overweight and DM emphasizes the importance of weight control measures to reduce the incidence of DM in the population. High rates of diabetic persons not aware of having DM in the population and insufficient cardiometabolic control among persons treated for DM stress the need for intensifying health care for diabetes.
Prolactin stimulates the proliferation of normal female cholangiocytes by differential regulation of Ca2+-dependent PKC isoforms
Authors: Taffetani Silvia , Glaser Shannon , Francis Heather , DeMorrow Sharon , Ueno Yoshiyuki , Alvaro Domenico , Marucci Luca , Marzioni Marco , Fava Giammarco , Venter Julie , Vaculin Shelley , Vaculin Bradley , Lam Ian Pak-Yan , Lee Vien Hoi-Yi , Gaudio Eugenio , Carpino Guido , Benedetti Antonio , Alpini Gianfranco
Published: July 2007

Background

Prolactin promotes proliferation of several cells. Prolactin receptor exists as two isoforms: long and short, which activate different transduction pathways including the Ca2+-dependent PKC-signaling. No information exists on the role of prolactin in the regulation of the growth of female cholangiocytes. The rationale for using cholangiocytes from female rats is based on the fact that women are preferentially affected by specific cholangiopathies including primary biliary cirrhosis. We propose to evaluate the role and mechanisms of action by which prolactin regulates the growth of female cholangiocytes.

Results

Normal cholangiocytes express both isoforms (long and short) of prolactin receptors, whose expression increased following BDL. The administration of prolactin to normal female rats increased cholangiocyte proliferation. In purified normal female cholangiocytes, prolactin stimulated cholangiocyte proliferation, which was associated with increased [Ca2+]i levels and PKCβ-I phosphorylation but decreased PKCα phosphorylation. Administration of an anti-prolactin antibody to BDL female rats decreased cholangiocyte proliferation. Normal female cholangiocytes express and secrete prolactin, which was increased in BDL rats. The data show that prolactin stimulates normal cholangiocyte growth by an autocrine mechanism involving phosphorylation of PKCβ-I and dephosphorylation of PKCα.

Conclusion

We suggest that in female rats: (i) prolactin has a trophic effect on the growth of normal cholangiocytes by phosphorylation of PKCβ-I and dephosphorylation of PKCα; and (iii) cholangiocytes express and secrete prolactin, which by an autocrine mechanism participate in regulation of cholangiocyte proliferation. Prolactin may be an important therapeutic approach for the management of cholangiopathies affecting female patients.
Bidirectional MHC molecule exchange between migratory and resident dendritic cells
Authors: de Heusch Magali , Blocklet Didier , Egrise Dominique , Hauquier Bernard , Vermeersch Marjorie , Goldman Serge , Moser Muriel
Published: July 2007

Dendritic cells (DCs) loaded extracorporeally with antigen can be used as an adjuvant in vivo. In this work, we analyzed the migration of transferred DC and monitored the phenotype of new migrants in the draining lymph nodes. It is surprising that we found that a majority of resident DCs expressed donor MHC molecules and that a proportion of injected DCs acquired host MHC molecules. These observations suggest that a bidirectional MHC molecule exchange occurs between migratory and resident DCs, a mechanism that may amplify antigen presentation in vivo.
Conditional overexpression of Stat3α in differentiating myeloid cells results in neutrophil expansion and induces a distinct, antiapoptotic and pro-oncogenic gene expression pattern
Authors: Redell Michele S , Tsimelzon Anna , Hilsenbeck Susan G , Tweardy David J
Published: July 2007

Normal neutrophil development requires G-CSF signaling, which includes activation of Stat3. Studies of G-CSF-mediated Stat3 signaling in cell culture and transgenic mice have yielded conflicting data regarding the role of Stat3 in myelopoiesis. The specific functions of Stat3 remain unclear, in part, because two isoforms, Stat3α and Stat3β, are expressed in myeloid cells. To understand the contribution of each Stat3 isoform to myelopoiesis, we conditionally overexpressed Stat3α or Stat3β in the murine myeloid cell line 32Dcl3 (32D) and examined the consequences of overexpression on cell survival and differentiation. 32D cells induced to overexpress Stat3α, but not Stat3β, generated a markedly higher number of neutrophils in response to G-CSF. This effect was a result of decreased apoptosis but not of increased proliferation. Comparison of gene expression profiles of G-CSF-stimulated, Stat3α-overexpressing 32D cells with those of cells with normal Stat3α expression revealed novel Stat3 gene targets, which may contribute to neutrophil expansion and improved survival, most notably Slc28a2, a purine nucleoside transporter, which is critical for maintenance of intracellular nucleotide levels and prevention of apoptosis, and Gpr65, an acid-sensing, G protein-coupled receptor with pro-oncogenic and antiapoptotic functions.
Novel Markers for the Prospective Isolation of Human MSC
Authors: BÜHRING HANS‐JÖRG , BATTULA VENKATA LOKESH , TREML SABRINA , SCHEWE BERNHARD , KANZ LOTHAR , VOGEL WICHARD
Published: July 2007

Abstract:  The isolation of mesenchymal stem cells (MSC) from primary tissue is hampered by the limited selectivity of available markers. So far, CD271 is one of the most specific markers for bone marrow (BM)‐derived MSC. In search of additional markers, monoclonal antibodies (mAbs) with specificity for immature cells were screened by flow cytometry for their specific reactivity with the rare CD271+ population. The recognized CD271+ populations were fractionated by fluorescence‐activated cell sorting and the clonogenic capacity of the sorted cells was analyzed for their ability to give rise to CFU‐F. The results showed that only the CD271bright but not the CD271dim population contained CFU‐F. Two‐color flow cytometry analysis revealed that only the CD271bright population was positive for the established MSC markers CD10, CD13, CD73, and CD105. In addition, a variety of mAbs specific for novel and partially unknown antigens selectively recognized the CD271bright population but no other BM cells. The new MSC‐specific molecules included the platelet‐derived growth factor receptor‐β (CD140b), HER‐2/erbB2 (CD340), frizzled‐9 (CD349), the recently described W8B2 antigen, as well as cell‐surface antigens defined by the antibodies W1C3, W3D5, W4A5, W5C4, W5C5, W7C6, 9A3, 58B1, F9‐3C2F1, and HEK‐3D6. In conclusion, the described markers are suitable for the prospective isolation of highly purified BM‐MSC. These MSC may be used as an improved starting population for transplantation in diseases like osteogenesis imperfecta, cartilage repair, and myocardial infarction.
Maintenance of Quiescent Hematopoietic Stem Cells in the Osteoblastic Niche
Authors: ARAI FUMIO , SUDA TOSHIO
Published: July 2007

Abstract:  Hematopoietic stem cells (HSCs) are responsible for blood cell production throughout an individual's lifetime. Interaction of HSCs with their specific microenvironments, known as stem cell niches, is critical for maintaining stem cell properties, including self‐renewal capacity and the ability to differentiate into multiple lineages. During postnatal life, the bone marrow (BM) supports both self‐renewal and differentiation of HSCs in specialized microenvironmental niches. In the adult BM, HSCs are located in the trabecular endosteum (osteoblastic niche) or sinusoidal perivascular (vascular niche) areas. Here we show that osteoblastic cells (OBs) are a critical component for sustaining slow‐cycling or quiescent HSCs. Interaction of HSCs with OBs through signaling and cell adhesion molecules maintains the balance in HSCs between cell division/proliferation and quiescence. In particular, the quiescent state is thought to be an essential mechanism to protect HSCs from stress and to sustain long‐term hematopoiesis.
Differentiation Potential of Histocompatible Parthenogenetic Embryonic Stem Cells
Authors: LENGERKE CLAUDIA , KIM KITAI , LEROU PAUL , DALEY GEORGE Q.
Published: July 2007

Abstract:  Embryonic stem cells (ESCs) hold unique promise for the development of cell replacement therapies, but derivation of therapeutic products from ESCs is hampered by immunological barriers. Creation of HLA‐typed ESC banks, or derivation of customized ESC lines by somatic cell nuclear transfer, have been envisioned for engineering histocompatible ESC‐derived products. Proof of principle experiments in the mouse have demonstrated that autologous ESCs can be obtained via nuclear transfer and differentiated into transplantable tissues, yet nuclear transfer remains a technology with low efficiency. Parthenogenesis provides an additional means for deriving ESC lines. In parthenogenesis, artificial oocyte activation initiates development without sperm contribution and no viable offspring are produced in the absence of paternal gene expression. Development proceeds readily to the blastocyst stage, from which parthenogenetic ESC (pESC) lines can be derived with high efficiency. We have recently shown that when pESC lines are derived from hybrid mice, early recombination events produce heterozygosity at the major histocompatibility complex (MHC) loci in some of these lines, enabling the generation of histocompatible differentiated cells that can engraft immunocompetent MHC‐matched mouse recipients. Here, we explore the differentiation potential of murine pESCs derived in our laboratory.
AMD3100 and CD26 Modulate Mobilization, Engraftment, and Survival of Hematopoietic Stem and Progenitor Cells Mediated by the SDF‐1/CXCL12‐CXCR4 Axis
Authors: BROXMEYER HAL E. , HANGOC GIAO , COOPER SCOTT , CAMPBELL TIMOTHY , ITO SHIGEKI , MANTEL CHARLIE
Published: July 2007

Abstract:  The chemokine stromal cell‐derived factor‐1 (SDF‐1/CXCL12) and its receptor, CXCR4, are involved in a number of facets of the regulation of hematopoiesis at the level of hematopoietic stem (HSCs) and progenitor (HPCs) cells. Modulation of this ligand–receptor interaction may be of clinical utility. We now report that: (1) the CC chemokine, macrophage inflammatory protein‐1α (MIP‐1α/CCL3) synergizes with AMD3100 (an antagonist of the binding of SDF‐1/CXCL12 to CXCR4) to rapidly mobilize HPCs to the blood of mice; moreover, the combination of granulocyte colony‐stimulating factor (G‐CSF) with AMD3100 and MIP‐1α/CCL3, given in a specific sequence, mobilizes the greatest number of HPCs compared to any combination of two of these mobilizing agents; (2) pretreatment of recipient mice with Diprotin A, an inhibitor of CD26/Dipeptidylpeptidase IV (DPPIV), enhances the competitive HSCs repopulating capacity of untreated donor cells; (3) the survival‐enhancing effects of SDF‐1/CXCL12 on HPCs subjected in vitro to delayed addition of growth factors (GFs) are mediated in part through the cell cycle‐related proteins p21cip1/waf1 (as assessed using p21cip1/waf1−/− and +/+ mice) and Mad2 (using Mad2 +/− and +/+ mice); and (4) deletion of CD26/DPPIV on mouse bone marrow cells increases the survival‐enhancing effects of SDF‐1/CXCL12 on HPCs. These results demonstrate the means to increase the mobilization of HPCs, the engrafting capability of HSCs, and responsiveness of HPCs to the survival‐enhancing activity of SDF‐1/CXCL12, effects that may be of practical value.
Inhibition of Tgfβ signaling by endogenous retinoic acid is essential for primary lung bud induction
Authors: Chen Felicia , Desai Tushar J. , Qian Jun , Niederreither Karen , Lü Jining , Cardoso Wellington V.
Published: July 2007

Disruption of retinoic acid (RA) signaling during early development results in severe respiratory tract abnormalities, including lung agenesis. Previous studies suggest that this might result from failure to selectively induce fibroblast growth factor 10 (Fgf10) in the prospective lung region of the foregut. Little is known about the RA-dependent pathways present in the foregut that may be crucial for lung formation. By performing global gene expression analysis of RA-deficient foreguts from a genetic [retinaldehyde dehydrogenase 2 (Raldh2)-null] and a pharmacological (BMS493-treated)mouse model, we found upregulation of a large number of Tgfβ targets. Increased Smad2 phosphorylation further suggested that Tgfβ signaling was hyperactive in these foreguts when lung agenesis was observed. RA rescue of the lung phenotype was associated with low levels of Smad2 phosphorylation and downregulation of Tgfβ targets in Raldh2-null foreguts. Interestingly, the lung defect that resulted from RA-deficiency could be reproduced in RA-sufficient foreguts by hyperactivating Tgfβ signaling with exogenous TGFβ1. Preventing activation of endogenous Tgfβsignaling with a pan-specific TGFβ-blocking antibody allowed bud formation and gene expression in the lung field of both Raldh2-null and BMS493-treated foreguts. Our data support a novel mechanism of RA-Tgfβ-Fgf10 interactions in the developing foregut, in which endogenous RA controls Tgfβ activity in the prospective lung field to allow local expression of Fgf10 and induction of lung buds.
TwoC. eleganshistone methyltransferases represslin-3EGF transcription to inhibit vulval development
Authors: Andersen Erik C. , Horvitz H. Robert
Published: July 2007

Studies of Schizosaccharomyces pombe and mammalian cells identified a series of histone modifications that result in transcriptional repression. Lysine 9 of histone H3 (H3K9) is deacetylated by the NuRD complex,methylated by a histone methyltransferase (HMT) and then bound by a chromodomain-containing protein, such as heterochromatin protein 1 (HP1),leading to transcriptional repression. A Caenorhabditis elegansNuRD-like complex and HP1 homologs regulate vulval development, but no HMT is known to act in this process. We surveyed all 38 putative HMT genes in C. elegans and identified met-1 and met-2 as negative regulators of vulval cell-fate specification. met-1 is homologous to Saccharomyces cerevisiae Set2, an H3K36 HMT that prevents the ectopic initiation of transcription. met-2 is homologous to human SETDB1, an H3K9 HMT that represses transcription. met-1 and met-2 (1)are each required for the normal trimethylation of both H3K9 and H3K36; (2)act redundantly with each other as well as with the C. elegans HP1 homologs; and (3) repress transcription of the EGF gene lin-3, which encodes the signal that induces vulval development. We propose that as is the case for Set2 in yeast, MET-1 prevents the reinitiation of transcription. Our results suggest that in the inhibition of vulval development, homologs of SETDB1, HP1 and the NuRD complex act with this H3K36 HMT to prevent ectopic transcriptional initiation.
Fgf8 induces pillar cell fate and regulates cellular patterning in the mammalian cochlea
Authors: Jacques Bonnie E. , Montcouquiol Mireille E. , Layman Erynn M. , Lewandoski Mark , Kelley Matthew W.
Published: July 2007

The mammalian auditory sensory epithelium (the organ of Corti) contains a number of unique cell types that are arranged in ordered rows. Two of these cell types, inner and outer pillar cells (PCs), are arranged in adjacent rows that form a boundary between a single row of inner hair cells and three rows of outer hair cells (OHCs). PCs are required for auditory function, as mice lacking PCs owing to a mutation in Fgfr3 are deaf. Here, using in vitro and in vivo techniques, we demonstrate that an Fgf8 signal arising from the inner hair cells is the key component in an inductive pathway that regulates the number, position and rate of development of PCs. Deletion of Fgf8 or inhibition of binding between Fgf8 and Fgfr3 leads to defects in PC development, whereas overexpression of Fgf8 or exogenous Fgfr3 activation induces ectopic PC formation and inhibits OHC development. These results suggest that Fgf8-Fgfr3 interactions regulate cellular patterning within the organ of Corti through the induction of one cell fate (PC) and simultaneous inhibition of an alternate fate (OHC) in separate progenitor cells. Some of the effects of both inhibition and overactivation of the Fgf8-Fgfr3 signaling pathway are reversible, suggesting that PC differentiation is dependent upon constant activation of Fgfr3 by Fgf8. These results suggest that PCs might exist in a transient state of differentiation that makes them potential targets for regenerative therapies.
IGF-I and insulin activate mitogen-activated protein kinase via the type 1 IGF receptor in mouse embryonic stem cells
Authors: Nguyen Thanh T , Sheppard Allan M , Kaye Peter L , Noakes Peter G
Published: July 2007

Although IGF-I and insulin are important modulators of preimplantation embryonic physiology, the signalling pathways activated during development remain to be elucidated. As a model of preimplantation embryos, pluripotent mouse embryonic stem cells were used to investigate which receptor mediated actions of physiological concentrations of IGF-I and insulin on growth measured by protein synthesis. Exposure of mouse embryonic stem (ES) cells to 1.7 pM IGF-I or 1.7 nM insulin for 4 h caused ~25% increase in protein synthesis when compared with cells cultured in basal medium containing BSA. Dose–response studies showed 100-fold higher potency of IGF-I that pointed to the type 1 IGF receptor as the mediating receptor for both ligands. This was confirmed using an anti-type 1 IGF receptor-blocking antibody (αIR3). Both 1.7 pM IGF-I and 1.7 nM insulin increased phosphorylation of the type 1 IGF receptor and this increase was blocked by αIR3, but the insulin receptor was not phosphorylated. Finally, binding of either agonist led to downstream phosphorylation of ERK1/2 mitogen-activated protein kinase (MAPK) also via IGF-1R as this was blocked by αIR3. Together, these results suggest that IGF-I and insulin modulate ES cell physiology through binding to the type 1 IGF receptor and subsequent activation of MAPK pathway.
Changes in major proteins in the embryonic capsule during immobilization (fixation) of the conceptus in the third week of pregnancy in the mare
Authors: Quinn B A , Hayes M A , Waelchli R O , Kennedy M W , Betteridge K J
Published: July 2007

During the third week of pregnancy, the equine conceptus is enclosed within a capsule, the glycan composition of which changes at around day 16 (ovulation = day 0) when the conceptus becomes immobilized (fixed) in the uterine lumen. Our objective was to characterize the process of fixation by identifying changes in major capsule-associated proteins. Individual equine conceptuses (n = 55) were collected transcervically by uterine lavage between days 13.5 and 26.5. Major proteins extracted from capsules were compared with those in fluids from the uterus and yolk sac by SDS–PAGE. Until day 14, a major capsule-associated protein that migrated at ~10 kDa was identified by N-terminal sequencing as equine β2 microglobulin (β2M). During fixation, β2M in the capsule underwent limited proteolysis to an ~8 kDa form lacking nine amino acids from the N terminus, and was subsequently degraded. Expression of β2M mRNA was detected in the yolk-sac wall tissues and endometrium between days 13.5 and 17.5. During this period, β2M in the capsule was evidently not part of a complex with major histocompatibility complex class 1 heavy α chain bands because these were undetectable in the capsule and uterine lavage. Uterocalin (p19) was detected in uterine lavage and capsule throughout fixation, but in yolk-sac fluid only before fixation. These studies indicate that intact β2M is a major protein associated with the embryonic capsule before fixation, after which it undergoes limited proteolysis to a truncated ~8 kDa form that remains in the capsule after the conceptus is immobilized.
A novel pyruvate kinase (PK-S) from boar spermatozoa is localized at the fibrous sheath and the acrosome
Authors: Feiden Sandra , Stypa Heike , Wolfrum Uwe , Wegener Gerhard , Kamp Günter
Published: July 2007

Boar spermatozoa contain a novel pyruvate kinase (PK-S) that is tightly bound at the acrosome of the sperm head and at the fibrous sheath in the principal piece of the flagellum, while the midpiece contains a soluble pyruvate kinase (PK). PK-S could not be solubilized by detergents, but by trypsin with no loss of activity. Purified PK-S as well as PK-S still bound to cell structures and soluble sperm PK have all kinetics similar to those of rabbit muscle PK-M1. The PK-S subunit had a relative molecular mass of 64 ± 1 × 103 (n = 3), i.e. slightly higher than that of PK-M1, and carried an N-terminal extension (NH2-TSEAM-COOH) that is lacking in native PK-M1. Evidence is provided that PK-S is encoded by the PKM gene. Antibodies produced against the N-terminus of purified PK-S (NH2-TSEAMPKAHMDAG-COOH) were specific for PK-S as they did not react with somatic PKs or soluble sperm PK, while anti-PK-M1 recognized both sperm PKs. Immunofluorescence microscopy showed anti-PK-S to label the acrosome and the flagellar principal piece, whereas the midpiece containing the mitochondria was labelled only by anti-PK-M1. Immunogold labelling confirmed the localization of PK-S at the acrosome. In the principal piece, both polyclonal anti-PK-M1 and anti-PK-S were found at the fibrous sheath. Our results suggest that PK-S is a major component in the structural organization of glycolysis in boar spermatozoa.