bluuebunny/crossref_metadata_2025 huggingface dataset:
Inappropriate Left Ventricular Mass in Patients With Primary Aldosteronism
Authors: Muiesan Maria Lorenza , Salvetti Massimo , Paini Anna , Agabiti-Rosei Claudia , Monteduro Cristina , Galbassini Gloria , Belotti Eugenia , Aggiusti Carlo , Rizzoni Damiano , Castellano Maurizio , Agabiti-Rosei Enrico
Published: July 2008

Assessment of appropriateness of left ventricular mass (LVM) for a given workload may better stratify hypertensive patients. Inappropriate LVM may reflect the interaction of genetic and neurohumoral factors other than blood pressure playing a significant role in myocardial growth. Primary aldosteronism (PA) represents a clinical model useful in assessing the effect of aldosterone increase on LVM. The aim of this study was to evaluate the inappropriateness of LVM in patients with PA. In 125 patients with PA (54 females; adrenal hyperplasia in 73 and adenoma in 52 patients) and in 125 age-, sex-, and blood pressure–matched, essential hypertensive patients, echocardiography was performed. The appropriateness of LVM was calculated by the ratio of observed LVM to the predicted value using a reference equation. In all of the subjects plasma renin activity and aldosterone, as well as clinic and 24-hour blood pressure, were measured. The prevalence of inappropriate LVM was greater in patients with traditionally defined left ventricular hypertrophy (70% and 44%, respectively;
P
=0.02) but also in patients without left ventricular hypertrophy (17% and 9%, respectively;
P
=0.085). In PA patients, a correlation was observed between the ratio of observed:predicted LVM and the ratio of aldosterone:plasma renin activity levels (
r
=0.29;
P
=0.003) or the postinfusion aldosterone concentration (
r
=0.44;
P
=0.004; n=42). In conclusion, in patients with PA, the prevalence of inappropriate LVM is increased, even in the absence of traditionally defined left ventricular hypertrophy. The increase in aldosterone levels could contribute to the increase of LV mass exceeding the amount needed to compensate hemodynamic load.
Trends in Twentieth-Century U.S. Snowfall Using a Quality-Controlled Dataset
Authors: Kunkel Kenneth E. , Palecki Michael , Ensor Leslie , Hubbard Kenneth G. , Robinson David , Redmond Kelly , Easterling David
Published: July 2008

A quality assessment of daily manual snowfall data has been undertaken for all U.S. long-term stations and their suitability for climate research. The assessment utilized expert judgment on the quality of each station. Through this process, the authors have identified a set of stations believed to be suitable for analysis of trends. Since the 1920s, snowfall has been declining in the West and the mid-Atlantic coast. In some places during recent years the decline has been more precipitous, strongly trending downward along the southern margins of the seasonal snow region, the southern Missouri River basin, and parts of the Northeast. Snowfall has been increasing since the 1920s in the lee of the Rocky Mountains, the Great Lakes–northern Ohio Valley, and parts of the north-central United States. These areas that are in opposition to the overall pattern of declining snowfall seem to be associated with specific dynamical processes, such as upslope snow and lake-effect snow that may be responding to changes in atmospheric circulation.
The Transformative Potential of Teacher Care as Described by Students in a Higher Education Access Initiative
Authors: Foster Karen C.
Published: July 2008

The “attitude—achievement gap” characterizing economically disadvantaged students of color is reexamined in a study of student perceptions of a higher education access program. Their descriptions of past and present experiences of teachers are contextualized in research citing the impact of stress, social stigma, and teacher misperceptions on economically disadvantaged students' capacity to engage with school. The contrast of their descriptions underscores the pivotal role that teachers play in shaping developing identities. Student descriptions reflect the aspects of their relationships with teachers that signify authentic care and commitment to their academic success. The findings indicate changes in students' understanding of the learning process and the connection between high school academic performance and college admission grounded in realistic self-assessment of their academic challenges. The findings suggest plasticity in educational identity development in older students and demonstrate the importance of including students' perspectives in research and evaluation of programs intended to support them.
The paradoxical processes of feminization in the professions: the case of established, aspiring and semi-professions
Authors: Bolton Sharon , Muzio Daniel
Published: July 2008

The past three decades have been characterized by dramatic labour market developments including the mass entry of women to exclusively male domains. Professional work is particularly indicative of this trend where growth in female membership has fuelled optimistic predictions of shattered glass ceilings and gender equality. This article seeks to challenge these predictions and to explore the associated assumptions linked with the feminization of work in the UK. It does so by focusing on three professional groups: law, teaching and management which, despite some substantial differences, present a common and recurrent theme in the gendered processes of professional projects that marginalize, downgrade and exploit women and women's work. It is argued that the fluidity of such processes lead to a series of paradoxes as the professions are increasingly dependent on the contribution of their female members and yet numerical feminization, without truly including women, serves to undermine and even reverse professional projects.
Dead men working: time and space in London's (`illegal') migrant economy
Authors: Nobil Ahmad Ali
Published: July 2008

This article explores human smuggling's consequences through a study of London's Pakistani immigrant economy, paying particular attention to the labour process and its experiential dimensions.The latter are unpacked in empirical context with due reference to literatures on illegal migration, as well as more recent writings on employment and `precariousness' that seek to make sense of the changing nature of work patterns under post-Fordist `flexible' regimes in the new global economy. All newly migrated (and some British born) Pakistanis working in ethnic economies endure long hours, poor working conditions, low pay and a general context of insecurity that is distinct from the unionized labour process that prevailed under Fordism. Smuggled migrants tend to deal with a specific set of constraints, however, including added material and psychological burdens stemming from the higher cost of migration and an inability to achieve `structural' embeddedness.
`We Don't Negotiate with Terrorists!': Legitimacy and Complexity in Terrorist Conflicts
Authors: Toros Harmonie
Published: July 2008

A key objection raised by terrorism scholars and policymakers against engaging in negotiations with terrorists is that it legitimizes terrorist groups, their goals and their means. Talking to them would serve only to incite more violence and weaken the fabric of democratic states, they argue. With the emergence of Al-Qaeda and its complex transnational structure, many have added another objection: Who does one talk to? Faced with such a multifaceted, horizontal organization, how does one engage? This article offers an alternative approach to the question of legitimacy and complexity in engaging with terrorism. Drawing from research in peace and conflict studies, it analyses how these two factors may in fact be conducive to a nonviolent resolution of conflicts involving terrorist violence. Using the conflicts in Northern Ireland and the southern Philippine region of Mindanao as illustrations, the article argues that the legitimation of `terrorist' groups through talks can be a means to transform a conflict away from violence, while complexity may in fact open up new possibilities for engagement. The article concludes by examining how the naming of a group as `terrorist' can and is often designed to forestall nonviolent responses to terrorism.
War on!
Authors: Simon Jonathan
Published: July 2008

'War on' is the leading form of anti-policy in the United States. Since the late 1950s we have seen wars on cancer, poverty, drugs and terror. Thus far, the most far-reaching of these, the war on crime, has transformed American democracy since the 1960s. The deformation of our population and institutions now requires not simply an end to that war and its extension (the 'War on Terror'), but the deployment of a new 'war on' to stimulate change in the governmentalities which have been established by the war on crime. A renewed 'war on cancer' offers great promise in this regard when analyzed in terms of the history of disease as a stimulus to change in governmentality, and specifically to the rise of biological citizenship.
Peacocks and wallflowers: (in)visibility with digital jewellery
Authors: Kettley Sarah
Published: July 2008

As a genre of Ubiquitous Computing, wearables inherited a paradigmatic ideal of disappearance and, until very recently, visibility was treated as a simplistic dichotomous issue of overt versus covert technology. In line with calls by theorists in New Media for oscillation between states of invisibility and reflection in the design of interfaces, this article presents findings from a networked jewellery project which reconceptualize this problem as both situated and dynamic, revealing that wearable artefacts segue between high states of visibility and disappearance just as they afford their wearers new ways of maintaining social presence.
Disputed Definitions and Fluid Identities: The Limitations of Social Profiling In Relation to Ethnic Youth Gangs
Authors: White Rob
Published: July 2008

This article provides a critique of social profiling in relation to ethnically identified youth gangs by considering the fluid nature of social identity and the ambiguities of gang formation. It begins by outlining the nature of youth group affiliation and association, and the multilayered ways in which social identity is constructed. This is followed by a brief review of key propositions relating to youth gangs, derived from international gang research over the last decade. The final section of the paper presents two models of social profiling, one of which is based upon actual criminal events, the other on prediction of `risk'. It is argued that anti-gang intervention based upon a type of social profiling that net-widens will most likely compound the very problem it is intended to address.
Western science and Islamic learners
Authors: Robottom Ian , Norhaidah Sharifah
Published: July 2008

This article reports on two research projects (one in Malaysia and one in Australia) that studied the experiences of Islamic background learners studying western science. Conceptually, this research program is conducted within a socially constructivist discourse and employs both quantitative and qualitative forms of data collection. The article illustrates ways in which learners' meaning-making in science education is shaped by faith and culture and has the potential to expand our grasp of the expressions, implications and limitations of the constructivist hypothesis in education. In this sense it has an `equality of opportunity' agenda by working to improve access to, and experience in, the science curriculum for Muslim students.
The internationalization of universities
Authors: Chan Wendy W.Y. , Dimmock Clive
Published: July 2008

Internationalization is a multifaceted concept, with many different interpretations, emphases and purposes. Its amorphous nature is captured in this comparative case study of the internationalization of two contrasting universities: one in the UK, the other in Hong Kong. The cases represent two distinct models of internationalization: the `internationalist' and the `translocalist'. A hypothetical third model, the globalist, is also suggested. The three models of internationalization capture different realities reflecting the importance of international, national and institutional contexts, as well as available opportunities and parameters of choice in decisions relating to internationalization.
The development of ESL provision in Australia, Canada, the USA and England, with conclusions for second language models in international schools
Authors: Carder Maurice
Published: July 2008

In this article the development of educational provision for second-language speakers in various English-speaking countries is traced. Conclusions are then drawn as to which are the best educational models for international schools, and an argument is made for the central positioning of ESL-and-mother-tongue departments as one entity in international school structures and curriculum planning, in order to capitalize on the knowledge and expertise of teachers in these departments and provide equity in the curriculum for ESL students.
Impact Damage Detection in Aircraft Composites Using Knowledge-based Reasoning
Authors: Mujica L.E. , Vehí J. , Staszewski W. , Worden K.
Published: July 2008

A hybrid reasoning methodology is applied to a complex aerospace structure, and its effectiveness is assessed in identifying and locating the position of impacts. Part of a commercial aircraft wing flap is impacted and time-varying strain response data from the structure are sensed using passive piezoceramic sensors. This structure can be regarded as a small scale version of part of a wing span with the corresponding features being a leading edge and trailing edge. The trailing edge is composed of aluminium skins with an aluminium honeycomb core, the leading edge of composite skins with a light weight honeycomb core, and the central section of thin composite material. Nine sensors, to detect time-varying strain response data, are distributed over the surface of the flap; two on the leading edge, two on the trailing edge, and five in the central section. The methodology combines the use of: (i) Case-Based Reasoning; in a `learning mode', an initial casebase is created with the principal features of the impact responses. When the system is working in an `operating mode', the data acquired by sensors are used to perform a diagnosis by analogy with the cases stored in the casebase: reusing and adapting old situations. (ii) The Wavelet Transform is used to extract principal features of a signal providing information about the impact locations. (iii) Self-Organizing Maps are trained as a classification tool in order to organize the old cases in memory with the purpose of speeding up the reasoning process. Finally, when old similar cases are retrieved, the impact location is obtained directly from heuristic considerations.
Psychometric Properties of Functional Balance Assessment in Children With Cerebral Palsy
Authors: Gan Sue-Mae , Tung Li-Chen , Tang Yue-Her , Wang Chun-Hou
Published: July 2008

Background. Children with cerebral palsy often suffer from a lack of balance compared with typically developing children. Because balance capacity is relevant to functional activities, reliable and valid functional balance measures are crucial for the pediatric clinical setting. Objective. This study examined the reliability and validity of 3 functional balance measures. Methods. Thirty children aged 60 to 142 months with Gross Motor Function Classification System (GMFCS) levels of I to IV were recruited. For test-retest reliability, the same physical therapist administered the Functional Reach Test (FRT), Berg Balance Scale (BBS), and Timed Up and Go (TUG) twice. For interrater reliability, the testing processes were video recorded and later scored by another therapist. For convergent validity, children with cerebral palsy received the Gross Motor Function Measures (GMFM), walking speed, and 10-second sit-to-stand test within 1 week and the results evaluated. Results. The 3 functional balance measures had excellent test-retest reliability (intraclass correlation coefficient [ICC] >0.95) and interrater reliability (ICC = 0.98-1.00). With regard to convergent validity, the BBS and the TUG were highly correlated with GMFM total score, walking speed, and the 10-second sit-to-stand test. The discriminate validity indicates that the FRT can distinguish children with cerebral palsy with different GMFCS levels, whereas the BBS total score and TUG failed to distinguish between children with cerebral palsy with GMFCS levels of I and II. Conclusion. The 3 functional balance measures are simple, valid, and reliable for examining children with cerebral palsy and are thus suitable for clinical practice.
Assisted Movement With Enhanced Sensation (AMES): Coupling Motor and Sensory to Remediate Motor Deficits in Chronic Stroke Patients
Authors: Cordo Paul , Lutsep Helmi , Cordo Linda , Wright W. Geoffrey , Cacciatore Timothy , Skoss Rachel
Published: July 2008

Background. Conventional methods of rehabilitation in patients with chronic, severe motor impairments after stroke usually do not lessen paresis. Objective. A novel therapeutic approach (assisted movement with enhanced sensation [AMES]) was employed in a medical device phase I clinical trial to reduce paresis and spasticity and, thereby, to improve motor function. Methods. Twenty subjects more than 1 year poststroke with severe motor disability of the upper or lower extremity were studied. A robotic device cycled the ankle or the wrist and fingers at 5°/s through ±17.5° in flexion and extension while the subject assisted this motion. Feedback of the subject's active torque was displayed on a monitor. Simultaneously, 2 vibrators applied a 60 pps stimulus to the tendons of the lengthening muscles, alternating from flexors to extensors as the joint rotation reversed from extension to flexion, respectively. Subjects treated themselves at home for 30 min/day for 6 months. Every other day prior to treatment, the therapy device performed automated tests of strength and joint positioning. Functional testing was performed prior to enrollment, immediately after completing the protocol, and 6 months later. Functional tests included gait and weight distribution (lower extremity subjects only) and the Stroke Impact Scale. Results. Most subjects improved on most tests, and gains were sustained for 6 months in most subjects. No safety problems arose. Conclusion. The AMES strategy appears safe and possibly effective in patients with severe chronic impairments. The mechanism underlying these gains is likely to be multifactorial.
Review: Therapeutic advances in pulmonary arterial hypertension
Authors: Boutet K. , Montani David , Jaïs Xavier , Yaïci Azzedine , Sitbon Oliver , Simonneau Gérald , Humbert Marc
Published: July 2008

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis, and vascular remodeling of small pulmonary arteries inducing increased pulmonary arterial resistance. Conventional treatment is based on life style modification and nonspecific treatment (warfarine, diuretics, oxygen). Calcium channel blockers are vasodilatators that have been shown to be of great efficacy in a very specific subpopulation of patients with PAH. For the majority of patients, specific PAH therapies are still lacking. Numerous studies evaluating prostacyclin agonists, endothelin-receptor antagonists, and phosphodiesterase type 5 inhibitors are now available to guide therapeutic choices. Despite those important advances there is still no cure for PAH. Fortunately, research is ongoing and many drugs show promises.
Citrullination of CXCL10 and CXCL11 by peptidylarginine deiminase: a naturally occurring posttranslational modification of chemokines and new dimension of immunoregulation
Authors: Loos Tamara , Mortier Anneleen , Gouwy Mieke , Ronsse Isabelle , Put Willy , Lenaerts Jean-Pierre , Van Damme Jo , Proost Paul
Published: July 2008

Interactions between chemokines and enzymes are vital in immunoregulation. Structural protein citrullination by peptidylarginine deiminase (PAD) has been associated with autoimmunity. In this report, we identified a novel naturally occurring posttranslational modification of chemokines, that is, the deimination of arginine at position 5 into citrulline of CXC chemokine ligand 10 (CXCL10) by rabbit PAD and human PAD2. Citrullination reduced (≥ 10-fold) the chemoattracting and signaling capacity of CXCL10 for CXC chemokine receptor 3 (CXCR3) transfectants; however, it did not affect CXCR3 binding. On T lymphocytes, though, citrullinated CXCL10 remained active but was again weaker than authentic CXCL10. PAD was also able to convert CXCL11, causing an impairment of CXCR3 signaling and T-cell activation, though less pronounced than for CXCL10. Similarly, receptor binding properties of CXCL11 were not altered by citrullination. However, deimination decreased heparin binding properties of both CXCL10 and CXCL11. Overall, chemokines are the first immune modulators reported of being functionally modified by citrullination. These data provide new structure-function dimensions for chemokines in leukocyte mobilization, disclosing an anti-inflammatory role for PAD. Additionally because citrullination has severe consequences for chemokine biology, this invites to reassess the involvement and impact of PAD and citrullinated peptides in inflammation, autoimmunity, and hematologic disorders.
Viscoelastic behaviour of human mesenchymal stem cells
Authors: Tan Samuel CW , Pan Wen X , Ma Gang , Cai Ning , Leong Kam W , Liao Kin
Published: July 2008

Background

In this study, we have investigated the viscoelastic behaviour of individual human adult bone marrow-derived mesenchymal stem cells (hMSCs) and the role of F-actin filaments in maintaining these properties, using micropipette aspiration technique together with a standard linear viscoelastic solid model.

Results

Under a room temperature of 20°C, the instantaneous and equilibrium Young's modulus, E
0 and E
∞, were found to be 886 ± 289 Pa and 372 ± 125 Pa, respectively, while the apparent viscosity, μ, was 2710 ± 1630 Pa·s. hMSCs treated with cytochalasin D up to 20 μM at 20°C registered significant drop of up to 84% in stiffness and increase of up to 255% in viscosity. At the physiological temperature of 37°C, E
0 and E
∞ have decreased by 42–66% whereas μ has increased by 95%, compared to the control. Majority of the hMSCs behave as viscoelastic solid with a rapid initial increase in aspiration length and it gradually levels out with time. Three other types of non-typical viscoelastic behavior of hMSCs were also seen.

Conclusion

hMSCs behave as viscoelastic solid. Its viscoelstic behaviour are dependent on the structural integrity of the F-actin filaments and temperature.
Comprehensive analysis of single-repeat R3 MYB proteins in epidermal cell patterning and their transcriptional regulation in Arabidopsis
Authors: Wang Shucai , Hubbard Leah , Chang Ying , Guo Jianjun , Schiefelbein John , Chen Jin-Gui
Published: July 2008

Background

Single-repeat R3 MYB transcription factors are critical components of the lateral inhibition machinery that mediates epidermal cell patterning in plants. Sequence analysis of the Arabidopsis genome using the BLAST program reveals that there are a total of six genes, including TRIPTYCHON (TRY), CAPRICE (CPC), TRICHOMELESS1 (TCL1), and ENHANCER of TRY and CPC 1, 2, and 3 (ETC1, ETC2 and ETC3) encoding single-repeat R3 MYB transcription factors that are approximately 50% identical to one another at the amino acid level. Previous studies indicate that these single-repeat R3 MYBs regulate epidermal cell patterning. However, each of the previous studies of these single-repeat R3 MYBs has been limited to an analysis of only a subset of these six genes, and furthermore, they have limited their attention to epidermal development in only one or two of the organs. In addition, the transcriptional regulation of these single-repeat R3 MYB genes remains largely unknown.

Results

By analyzing multiple mutant lines, we report here that TCL1 functions redundantly with other single-repeat R3 MYB transcription factors to control both leaf trichome and root hair formation. On the other hand, ETC1 and ETC3 participate in controlling trichome formation on inflorescence stems and pedicles. Further, we discovered that single-repeat R3 MYBs suppress trichome formation on cotyledons and siliques, organs that normally do not bear any trichomes. By using Arabidopsis protoplast transfection assays, we found that all single-repeat R3 MYBs examined interact with GL3, and that GL1 or WER and GL3 or EGL3 are required and sufficient to activate the transcription of TRY, CPC, ETC1 and ETC3, but not TCL1 and ETC2. Furthermore, only ETC1's transcription was greatly reduced in the gl3 egl3 double mutants.

Conclusion

Our comprehensive analysis enables us to draw broader conclusions about the role of single-repeat R3 MYB gene family than were possible in the earlier studies, and reveals the genetic basis of organ-specific control of trichome formation. Our findings imply the presence of multiple mechanisms regulating the transcription of single-repeat R3 MYB genes, and provide new insight into the lateral inhibition mechanism that mediates epidermal cell patterning.
Analysis of the grape MYB R2R3 subfamily reveals expanded wine quality-related clades and conserved gene structure organization across Vitis and Arabidopsis genomes
Authors: Matus José Tomás , Aquea Felipe , Arce-Johnson Patricio
Published: July 2008

Background

The MYB superfamily constitutes the most abundant group of transcription factors described in plants. Members control processes such as epidermal cell differentiation, stomatal aperture, flavonoid synthesis, cold and drought tolerance and pathogen resistance. No genome-wide characterization of this family has been conducted in a woody species such as grapevine. In addition, previous analysis of the recently released grape genome sequence suggested expansion events of several gene families involved in wine quality.

Results

We describe and classify 108 members of the grape R2R3 MYB gene subfamily in terms of their genomic gene structures and similarity to their putative Arabidopsis thaliana orthologues. Seven gene models were derived and analyzed in terms of gene expression and their DNA binding domain structures. Despite low overall sequence homology in the C-terminus of all proteins, even in those with similar functions across Arabidopsis and Vitis, highly conserved motif sequences and exon lengths were found. The grape epidermal cell fate clade is expanded when compared with the Arabidopsis and rice MYB subfamilies. Two anthocyanin MYBA related clusters were identified in chromosomes 2 and 14, one of which includes the previously described grape colour locus. Tannin related loci were also detected with eight candidate homologues in chromosomes 4, 9 and 11.

Conclusion

This genome wide transcription factor analysis in Vitis suggests that clade-specific grape R2R3 MYB genes are expanded while other MYB genes could be well conserved compared to Arabidopsis. MYB gene abundance, homology and orientation within particular loci also suggests that expanded MYB clades conferring quality attributes of grapes and wines, such as colour and astringency, could possess redundant, overlapping and cooperative functions.
Pre-clinical characterization of GMP grade CCL21-gene modified dendritic cells for application in a phase I trial in Non-Small Cell Lung Cancer
Authors: Baratelli Felicita , Takedatsu Hiroko , Hazra Saswati , Peebles Katherine , Luo Jie , Kurimoto Pam S , Zeng Gang , Batra Raj K , Sharma Sherven , Dubinett Steven M , Lee Jay M
Published: July 2008

Background

Our previous studies have demonstrated that transduction of human dendritic cells (DC) with adenovirus encoding secondary lymphoid chemokine, CCL21, led to secretion of biologically active CCL21 without altering DC phenotype or viability. In addition, intratumoral injections of CCL21-transduced DC into established murine lung tumors resulted in complete regression and protective anti-tumor immunity. These results have provided the rationale to generate a clinical grade adenoviral vector encoding CCL-21 forex vivotransduction of human DC in order to assess intratumoral administration in late stage human lung cancer.

Methods

In the current study, human monocyte-derived DC were differentiated by exposure to GM-CSF and IL-4 from cryopreserved mononuclear cells obtained from healthy volunteers. Transduction with clinical grade adenoviral vector encoding CCL21 (1167 viral particles per cell) resulted in secretion of CCL21 protein.

Results

CCL21 protein production from transduced DC was detected in supernatants (24–72 hours, 3.5–6.7 ng/4–5 × 106cells). DC transduced with the clinical grade adenoviral vector were > 88% viable (n = 16), conserved their phenotype and maintained integral biological activities including dextran uptake, production of immunostimulatory cytokines/chemokines and antigen presentation. Furthermore, supernatant from CCL21-DC induced the chemotaxis of T2 cellsin vitro.

Conclusion

Viable and biologically active clinical grade CCL21 gene-modified DC can be generated from cryopreserved PBMC.
Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium
Authors: Elzarrad M Khair , Haroon Abu , Willecke Klaus , Dobrowolski Radoslaw , Gillespie Mark N , Al-Mehdi Abu-Bakr
Published: July 2008

Background

The modulation of gap junctional communication between tumor cells and between tumor and vascular endothelial cells during tumorigenesis and metastasis is complex. The notion of a role for loss of gap junctional intercellular communication in tumorigenesis and metastasis has been controversial. While some of the stages of tumorigenesis and metastasis, such as uncontrolled cell division and cellular detachment, would necessitate the loss of intercellular junctions, other stages, such as intravasation, endothelial attachment, and vascularization, likely require increased cell-cell contact. We hypothesized that, in this multi-stage scheme, connexin-43 is centrally involved as a cell adhesion molecule mediating metastatic tumor attachment to the pulmonary endothelium.

Methods

Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. Calcein Orange Red AM dye transfer by fluorescence imaging was used to evaluate the gap junction function.

Results

Adhesion of breast cancer cells to the pulmonary endothelium increased with cancer cells overexpressing connexin-43 and markedly decreased with cells expressing dominant-negative connexin-43. Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas in vitro and in vivo, and in areas of intratumor blood vessels and in micrometastatic foci.

Conclusion

Connexin-43 facilitates metastatic 'homing' by increasing adhesion of cancer cells to the lung endothelial cells. The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis.
Human infrapatellar fat pad-derived stem cells express the pericyte marker 3G5 and show enhanced chondrogenesis after expansion in fibroblast growth factor-2
Authors: Khan Wasim S , Tew Simon R , Adesida Adetola B , Hardingham Timothy E
Published: July 2008

Introduction

Infrapatellar fat pad (IPFP) is a possible source of stem cells for the repair of articular cartilage defects. In this study, adherent proliferative cells were isolated from digests of IPFP tissue. The effects of the expansion of these cells in fibroblast growth factor-2 (FGF-2) were tested on their proliferation, characterisation, and chondrogenic potential.

Methods

IPFP tissue was obtained from six patients undergoing total knee replacement, and sections were stained with 3G5, alpha smooth muscle actin, and von Willebrand factor to identify different cell types in the vasculature. Cells were isolated from IPFP, and both mixed populations and clonal lines derived from them were characterised for cell surface epitopes, including 3G5. Cells were expanded with and without FGF-2 and were tested for chondrogenic differentiation in cell aggregate cultures.

Results

3G5-positive cells were present in perivascular regions in tissue sections of the IPFP, and proliferative adherent cells isolated from the IPFP were also 3G5-positive. However, 3G5 expression was on only a small proportion of cells in all populations and at all passages, including the clonally expanded cells. The cells showed cell surface epitope expression similar to adult stem cells. They stained strongly for CD13, CD29, CD44, CD90, and CD105 and were negative for CD34 and CD56 but were also negative for LNGFR (low-affinity nerve growth factor receptor) and STRO1. The IPFP-derived cells showed chondrogenic differentiation in cell aggregate cultures, and prior expansion with FGF-2 enhanced chondrogenesis. Expansion in FGF-2 resulted in greater downregulation of many cartilage-associated genes, but on subsequent chondrogenic differentiation, they showed stronger upregulation of these genes and this resulted in greater matrix production per cell.

Conclusion

These results show that these cells express mesenchymal stem cell markers, but further work is needed to determine the true origin of these cells. These results suggest that the expansion of these cells with FGF-2 has important consequences for facilitating their chondrogenic differentiation.
The proteome of Toxoplasma gondii: integration with the genome provides novel insights into gene expression and annotation
Authors: Xia Dong , Sanderson Sanya J , Jones Andrew R , Prieto Judith H , Yates John R , Bromley Elizabeth , Tomley Fiona M , Lal Kalpana , Sinden Robert E , Brunk Brian P , Roos David S , Wastling Jonathan M
Published: July 2008

Background

Although the genomes of many of the most important human and animal pathogens have now been sequenced, our understanding of the actual proteins expressed by these genomes and how well they predict protein sequence and expression is still deficient. We have used three complementary approaches (two-dimensional electrophoresis, gel-liquid chromatography linked tandem mass spectrometry and MudPIT) to analyze the proteome of Toxoplasma gondii, a parasite of medical and veterinary significance, and have developed a public repository for these data within ToxoDB, making for the first time proteomics data an integral part of this key genome resource.

Results

The draft genome for Toxoplasma predicts around 8,000 genes with varying degrees of confidence. Our data demonstrate how proteomics can inform these predictions and help discover new genes. We have identified nearly one-third (2,252) of all the predicted proteins, with 2,477 intron-spanning peptides providing supporting evidence for correct splice site annotation. Functional predictions for each protein and key pathways were determined from the proteome. Importantly, we show evidence for many proteins that match alternative gene models, or previously unpredicted genes. For example, approximately 15% of peptides matched more convincingly to alternative gene models. We also compared our data with existing transcriptional data in which we highlight apparent discrepancies between gene transcription and protein expression.

Conclusion

Our data demonstrate the importance of protein data in expression profiling experiments and highlight the necessity of integrating proteomic with genomic data so that iterative refinements of both annotation and expression models are possible.
Pivotal Advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis
Authors: Andersson Åsa , Covacu Ruxandra , Sunnemark Dan , Danilov Alexandre I , Dal Bianco Assunta , Khademi Mohsen , Wallström Erik , Lobell Anna , Brundin Lou , Lassmann Hans , Harris Robert A
Published: July 2008

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the CNS, most frequently starting with a series of bouts, each followed by complete remission and then a secondary, progressive phase during which the neurological deficit increases steadily. The underlying molecular mechanisms responsible for disease progression are still unclear. Herein, we demonstrate that high mobility group box chromosomal protein 1 (HMGB1), a DNA-binding protein with proinflammatory properties, is evident in active lesions of MS and experimental autoimmune encephalomyelitis (EAE) and that HMGB1 levels correlate with active inflammation. Furthermore, the expression of the innate HMGB1 receptors—receptor for advanced glycation end products, TLR2, and TLR4—was also highly increased in MS and rodent EAE. Additionally, in vitro activation of rodent CNS-derived microglia and bone marrow-derived macrophages demonstrated that microglia were equally as capable as macrophages of translocating HMGB1 following LPS/IFN-γ stimulation. Significant expression of HMGB1 and its receptors on accumulating activated macrophages and resident microglia may thus provide a positive feedback loop that amplifies the inflammatory response during MS and EAE pathogenesis.
Teaching grammar to school-aged children with specific language impairment using Shape Coding
Authors: Ebbels Susan
Published: July 2008

This paper describes an approach to teaching grammar which has been designed for school-aged children with specific language impairment (SLI). The approach uses shapes, colours and arrows to make the grammatical rules of English explicit. Evidence is presented which supports the use of this approach with older children in the areas of past tense morphology, comprehension of dative structures and comparative questions. I conclude that there is sufficient evidence that this kind of intervention can be effective with these older children. This challenges the current move to reduce direct intervention for school-aged children.
Constructing the ‘Genuine American City’: neo-traditionalism, New Urbanism and neo-liberalism in the remaking of downtown Milwaukee
Authors: Kenny Judith T. , Zimmerman Jeffrey
Published: July 2008

In this era of competitive capitalism, American cities have sought to orchestrate strategies of both image and material regeneration. The recent revival of central Milwaukee demonstrates the convergence of three discourses in the city’s image-making and redevelopment schemes. These three are the cultural discourse of neo-traditionalism, the planning discourse of the New Urbanism, and neo-liberalism in the arena of public policy. This paper examines the convergence of these three as a case study of the role of culture in contemporary urban development. We structure our argument in three parts. First, we give attention to a campaign designed to promote metropolitan Milwaukee, reflecting its most recent incarnation as a city that nostalgically embraces its industrial past. The promotional image includes the city’s grounding in traditional Midwestern values, the cultural capital represented by its late nineteenth-century industrial landscape, and its claim to the title ‘Genuine American City’. This reflection on ‘genuineness’ and ‘tradition’ reveals nostalgia for an earlier era that appeals to a significant segment of the population. The second portion of the paper examines the links between Milwaukee’s ‘traditional’ urban form, its design and investment strategies, and the city’s evolving New Urbanist landscape. The third section addresses the mayor’s neo-liberal views as they relate to his particular vision of Milwaukee. We conclude our exploration by examining the potential consequences of such neo-traditional ideologies for various communities within the city.
Educational attainments of children with specific language impairment at year 6
Authors: Knox Emma
Published: July 2008

The present study examined the performance of a group of children with Specific Language Impairment (SLI) in National Curriculum Key Stage 2 (KS2) assessments of key curricular subjects. One hundred children (86 boys and 14 girls), who previously had all been in full-time attendance at specialist provision in the form of language units, participated in the study. The sample of participants were recruited in their final year of primary school education (year 6) and were divided into two groups, matched for ability, defined by the nature of their current educational placement. The Mainstream Education group comprised 50 children attending mainstream education with or without some level of additional support. The Special Education group consisted of 50 children attending special education in the form of either a language unit, a language school, or a special school. Participants’ performance in the National Curriculum KS2 assessments was measured, together with an examination of assessment procedures concerning the application of special testing arrangements. It was found that participants performed poorly relative to national levels of expectation and achievement across the curricular subjects of English, mathematics and science in both KS2 tests and teacher assessments. The Mainstream Education group of participants was found to perform significantly better than the Special Education group in the mathematics and science tests. Furthermore, special arrangements were made for a large number of participants who did take the tests.
Phase I-II Trial of Bortezomib Plus Oral Cyclophosphamide and Prednisone in Relapsed and Refractory Multiple Myeloma
Authors: Reece Donna E. , Rodriguez Giovanni Piza , Chen Christine , Trudel Suzanne , Kukreti Vishal , Mikhael Joseph , Pantoja Mariela , Xu Wei , Stewart A. Keith
Published: July 2008

Purpose

The combination of oral weekly cyclophosphamide and alternate day prednisone is a convenient regimen for relapsed/refractory multiple myeloma (MM), and we sought to improve its efficacy by adding bortezomib, a proteasome inhibitor with proven antimyeloma activity.

Patients and Methods

We conducted a phase I-II trial evaluating six dose levels to define the maximum tolerated dose (MTD) of this combination in relapsed/refractory MM. An additional 10 patients were evaluated at the highest dose level reached.

Results

Thirty-seven patients were treated on this study. The MTD was not defined. Both of the highest dose levels of bortezomib tested (1.3 mg/m2 on days 1, 4, 8, and 11 and 1.5 mg/m2 on days 1, 8, and 15, each on a 28-day cycle) could be safely given with cyclophosphamide 300 mg/m2 per week and prednisone. At these dose levels, the overall response rate was 95% (complete responses [CR] plus partial response plus minimal response), with CR observed in more than 50% of patients. The weekly bortezomib regimen resulted in fewer instances of grade 3 thrombocytopenia and grade 1 to 2 peripheral neuropathy; the 1-year progression-free and overall survival probabilities with this dose level were 83% (95% CI, 73% to 96%) and 100%, respectively.

Conclusion

Weekly bortezomib 1.5 mg/m2 plus oral cyclophosphamide and prednisone produces an unprecedented response rate and encouraging 1-year survival in relapsed/refractory patients with MM. Further evaluation of this promising regimen is warranted both in relapsed and newly diagnosed disease.
A Convenient Method for the Synthesis of (Z)-α-Fluoroacrylates: Lewis Base-catalyzed Carbonyl Fluoroolefination Using Fluoro(trimethylsilyl)ketene Ethyl Trimethylsilyl Acetal
Authors: Michida Makoto , Mukaiyama Teruaki
Published: July 2008

A highly useful method is established for the stereoselective synthesis of (Z)-α-fluoroacrylates from various aldehydes and fluoro(trimethylsilyl)ketene ethyl trimethylsilyl acetal in the presence of a Lewis base catalyst. The ketene acetal, easily prepared from ethyl fluoroacetate, affords α-fluoroacrylates in high yields with excellent Z stereoselectivities under mild conditions.
Aerosol-assisted Rapid Fabrication of Well-dispersed and Highly Doped Titanium-containing Mesoporous Silica Microspheres
Authors: Yamauchi Yusuke , Kimura Tatsuo
Published: July 2008

Ti-containing mesoporous silica microspheres with high Ti content are prepared by a spray-drying method. Ti species are well-dispersed and highly doped in the silicate frameworks without collapse of mesoporous structures.
Evidence-based medicine as viewed by key decision-makers of health plans in southern Brazil
Authors: Tiburi Marcelo F
Published: July 2008

Evidence-based Medicine (EBM) is a tool that is becoming increasingly important for management in the health-care system, particularly in managed care. However, there are several doubts over how health plan managers address this issue. This study was designed to verify the current status of EBM in health plans as viewed by their key administrative decision-makers in southern Brazil. We present and discuss participants' agreement to predefined statements about: their level of knowledge on EBM, practitioners' and consumers' behaviour regarding EBM, potential effects for health-care plans by implementing EBM, and attitudes and interest of health-care plans toward evidence-based guidelines. We conclude that there is a need to establish educational efforts oriented to health-care plan managers regarding EBM, considering its good acceptance by managers and an expectation that EBM can help solve several dilemmas faced by health-care plans in southern Brazil.
Measuring primary care services performance: issues and opportunities from a home care pilot experience in the Tuscan health system
Authors: Cinquini Lino , Vainieri Milena
Published: July 2008

In recent years in Italy, as in other European countries, profound changes have been introduced in health care both at central and regional levels. Most of them were oriented towards a shift from ‘hospital-centred’ health care to health care based more on primary care services. This transition pursues two objectives: giving more effective responses to citizens' needs and reducing public health expenditure. Changes that involve organizational structure must also be carried out with the introduction of measurement tools that can help in planning and can control the changes. The paper provides the results obtained through the experience of modelling a measurement system for primary care carried out in 2004 and 2005 by some territorial managers and controllers in the Tuscan Health system, and the main issues in measuring primary care services emerging from this pilot experience focused on integrated home care services.