bluuebunny/crossref_metadata_2025 huggingface dataset:
¿Fue moderna la literatura española del siglo XVIII?: Análisis de la evaluación decimonónica
Authors: Sánchez-Llama Iñigo
Published: September 2008

La evaluación de la literatura española setecentista experimenta una significativa evolución durante el período decimonónico. En el primer tercio del siglo XIX el paradigma romántico favorece interpretaciones que señalan los vínculos de las letras dieciochescas con hábitos culturales no modernos vinculados al Antiguo Régimen. Desde el último tercio de la centuria, de todos modos, empiezan a producirse valoraciones que apuntan la modernidad literaria de ciertos textos setecentistas. El análisis de la pluralidad de estos discursos críticos en el XIX es relevante para confirmar los indudables rasgos modernos de la literatura española escrita durante la Ilustración. Estas lecturas críticas configuran asimismo un complejo corpus textual en el que puede percibirse la articulación teórica, en mayor o menor grado, de los valores estéticos consagrados por la modernidad filosófica.
"The Feminine Touch Has Not Been Wanting": Women Librarians at Camp Zachary Taylor, 1917–1919
Authors: Daniels Caroline
Published: September 2008

During World War I the American Library Association established libraries at military camps throughout the country as part of its Library War Service program. The experience of the female library workers at Camp Zachary Taylor in Louisville, Kentucky, attests to both the essential nature of their work and the limitations women faced working in camp libraries during World War I. The ALA's published records create the impression that this library was staffed and run by men, except for the hospital librarian. The unpublished and locally published records of this library, however, reveal that women were quite involved in staffing and even leading the library. Despite regulations and attitudes that might have limited their involvement, women contributed significantly to the operation of this and other wartime libraries.
The Public Library as Instrument of Colonialism: The Case of the Netherlands East Indies
Authors: Fitzpatrick Elizabeth B.
Published: September 2008

Between 1918 and 1926, fully 2,500 public libraries were established by the government of the Netherlands East Indies colony, mostly in towns and villages throughout the huge archipelago that became present-day Indonesia. Though popular with newly literate local people, the material in the libraries was designed to inculcate "Western" values and further the colonial situation. I will describe the historical and literary setting of this phenomenon. My analysis includes a close reading of remarks made by one of the responsible agency's longtime directors.
Contradictions of Corporate Benevolence: Industrial Libraries in the Southern Textile Industry, 1920–1945
Authors: Dredge Bart
Published: September 2008

Most company or industrial libraries emerged during the years immediately prior to World War I, often with the assistance of the Young Men's Christian Association. Many of these libraries and reading rooms were vital components of company welfare plans that eased the difficulties of factory work and life for countless industrial employees and their families. This article focuses on the southern textile industry to explore the tension between welfare benevolence and the subordination of industrial workers. Through a case study of one of the largest textile districts in the American South, it examines how company libraries and reading rooms helped create worker compliance and loyalty under the guise of corporate benevolence.
Clinicians’ Folk Taxonomies of Mental Disorders
Authors: Flanagan Elizabeth H. , Blashfield Roger K.
Published: September 2008

Abstract:
Using methods from anthropology and cognitive psychology, this study investigated the relationship between clinicians’ folk taxonomies of mental disorder and the Diagnostic and Statistical Manual of Mental Disorders (DSM). Expert and novice psychologists were given sixty-seven DSM-IV diagnoses, asked to discard unfamiliar diagnoses, put the remaining diagnoses into groups that had “similar treatments” using hierarchical (making more inclusive and less inclusive groups) and dimensional (placing groups in a two-dimensional space) methodologies, and give names to the groups in their taxonomies. Clinicians were familiar with a substantially smaller number of diagnoses than are in the DSM. Cultural consensus analysis and follow-up residual agreement analysis revealed similarities across clinicians’ folk taxonomies. Correlations between folk taxonomies and the DSM were moderate. Cluster analysis showed that clinicians preserved DSM higher order categories (e.g., mood disorders) but not the Axis I–Axis II distinction. This study suggests important differences between the way clinicians conceptualize mental disorders and the organization of the DSM-IV.
From Deficit to Desire: A Philosophical Reconsideration of Action Models of Psychopathology
Authors: Davidson Larry , Shahar Golan
Published: September 2008

Abstract:
Emerging action perspectives on psychopathology depict individuals as actively shaping those environmental conditions that then impact on their risk for psychopathology, resilience in the face of it, and successful recovery from it. This view, although having important implications for research and clinical practice, has yet to be articulated in terms of its underlying philosophical framework. To begin to address this challenge, we situate action theory in the context of the writings of Deleuze and Guattari, who, in their seemingly anti-psychiatric series entitled Capitalism and Schizophrenia , argue for the central role of human agency as a fundamentally active force in determining subjective life. Within this context, they propose an alternative approach to the current deficit focus of much psychopathology research, replacing the notion of deficit with a fundamentally productive notion of desire (what they call “desiring-production”). After our exposition of this philosophical perspective on human agency, implications of this approach for action-informed research and clinical practice are discussed.
University Challenges: Explaining Institutional Change in Higher Education
Authors: Ansell Ben W.
Published: September 2008

Higher education policy has been subject to considerable reform in OECD states over the past two decades. Some states have introduced tuition fees, others have massively increased public funding for higher education, and still others remain in stasis, retaining the elitist model with which they began the postwar era. This article develops the argument that higher education policy in the OECD is driven by a set of partisan choices within a trilemma between the level of enrollment, the degree of subsidization, and the overall public cost of higher education. The author develops a formal model of the micromechanisms underlying movements within this trilemma, noting the importance of partisan politics, existing enrollment, tax structure, and access. These propositions are tested statistically on a sample of twenty-two OECD countries and through case histories of higher education reform in England, Sweden, and Germany.
Bilateral Treaties and The Most-Favored-Nation Clause: The Myth of Trade Liberalization in the Nineteenth Century
Authors: Accominotti Olivier , Flandreau Marc
Published: September 2008

Textbook accounts of the Anglo-French trade agreement of 1860 argue that it heralded the beginning of a liberal trading order. This alleged success holds much interest from a modern policy point of view, for it rested on bilateral negotiations and most-favored-nation clauses. With the help of new data on international trade (the RICardo database), the authors provide empirical evidence and find that the treaty and subsequent network of MFN trade agreements coincided with the end of a period of unilateral liberalization across the world. They also find that it did not contribute to expanding trade at all. This is contrary to a deeply rooted belief among economists, economic historians, and political scientists. The authors draw a number of policy lessons that run counter to the conventional wisdom and raise skepticism toward the ability of bilateralism and MFN arrangements to promote trade liberalization.
Toward a New Theory of Institutional Change
Authors: Weyland Kurt
Published: September 2008

Going beyond historical and rational choice institutionalism, this article elaborates the core of a new theory that can account for the discontinuous, disproportionate, and frequently wave like-nature of institutional change. Cognitive-psychological findings on shifts in actors' propensity for assuming risk help explain why periods of institutional stasis can be followed by dramatic breakthroughs as actors eventually respond to a growing problem load with efforts at bold transformation. And insights on boundedly rational learning explain why solutions to these problems often occur as emulation of other countries' innovations and experiences. The new approach, which elucidates both the demand and the supply side of institutional change, is illustrated through an analysis of the transformation of developmental states, welfare states, and political regimes.
Embedding Neoliberal Reform in Latin America
Authors: Kurtz Marcus J. , Brooks Sarah M.
Published: September 2008

Although research in the advanced industrial nations has identified a supportive link between an expanded public sector role and economic openness, studies of the developing world have been much less sanguine about the possibilities of broader state intervention in the context of economic liberalization. The authors investigate the possibility that governments in Latin America may “embed” economic openness in a broader public sector effort. They find that while several countries have moved toward an orthodox neoliberal model with minimal state interventions, other Latin American governments have maintained a broader public sector presence on the supply side of the economy while pursuing deep liberalization. They call the latter strategy “embeddedneoliberalism,” to distinguish it from the more egalitarian ambitions of postwar embedded liberalism. Cross-sectional time-series analysis reveals that embedded neoliberal strategies in Latin America have grown out of a legacy of advanced import-substitution industrialization and have been promoted by nonleft governments, except in cases where labor is very strong. The orthodox neoliberal model, by contrast, has emerged where postwar industrial development was attenuated and where labor unions were weakened considerably by the debt crisis.
Increased Plasma Concentrations of Cytoskeletal and Ca2+-Binding Proteins and Their Peptides in Psoriasis Patients
Authors: Plavina Tatiana , Hincapie Marina , Wakshull Eric , Subramanyam Meena , Hancock William S
Published: September 2008

Background: The mechanisms underlying psoriatic pathogenesis are not fully understood and might be elucidated by identifying novel disease-related molecular markers, including autoantigens.

Methods: We used 2 proteomic methods to analyze plasma samples from 20 psoriasis patients and 20 matched healthy donors. The first method focused on evaluating changes in glycoprotein concentrations and the plasma proteome, and the second method assessed endogenous proteolytic activity by analyzing the low molecular weight component of plasma.

Results: The integrated proteomic and peptidomic analysis identified a number of proteins and their fragments present at different concentrations in the plasma of psoriasis patients and healthy donors. We used ELISA to independently verify the changes in the concentrations of several of these proteins. One intriguing finding, increased concentrations of cytoskeletal and actin-binding proteins and their peptides in psoriatic plasma, suggested disease-related cell leakage of these proteins and their increased proteolysis. Among the increased proteins and peptides were thymosin β 4, talin 1, actin γ, filamin, and profilin. Increased concentrations of Ca2+-binding proteins calgranulins A and B in psoriatic plasma were also observed, confirming previous reports, and appeared to be relevant to the increase of cytoskeletal components. Another notable change in psoriatic plasma was a striking decrease in fibrinogen fragments.

Conclusions: The identified increased concentrations of cytoskeletal proteins, their peptides, and calgranulins in psoriatic plasma, as well as the underlying altered protease activity, are proposed to be related to psoriasis pathogenesis.
Abnormal Matrix Remodeling in Adolescents and Young Adults with Kawasaki Disease Late after Onset
Authors: Lin Ming-Tai , Chen Shyh-Jye , Ho Yi-Lwun , Huang Kuo-Chin , Chen Chun-An , Chiu Shuenn-Nan , Sun Li-Chuan , Lee Wen-Jeng , Chen Hui-Chi , Wang Jou-Kou , Wu Mei-Hwan
Published: September 2008

Background: Patients with a history of Kawasaki disease (KD), have been found to have pericoronary and myocardial fibrosis. Serum biomarkers of fibrosis may be sensitive indices for detection of these late cardiac complications in KD patients.

Methods: We studied a cohort of 60 adolescents and young adults comprising 10 KD patients with persistent coronary artery lesions (CAL) occurring at a mean (SD) time of 14.5 (4.4) years after disease onset, 25 KD patients with no CAL after disease onset, and 25 healthy age-matched volunteers. We compared laboratory data from the patients and volunteers, including lipid profile, liver function, amino-terminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), and MMP-9:TIMP-1 ratios. Severity of CAL was determined on the basis of computed tomography determinations of the frequency of aneurysms and the extent of coronary stenosis/occlusion, thrombosis, and calcification.

Results: Increased PIIINP and decreased MMP-9 and TIMP-1 concentrations and decreased MMP-9:TIMP-1 ratios were found not only in KD patients with persistent CAL but also in KD patients without CAL, although to a lesser extent in the latter group. In KD patients, the concentrations of PIIINP were positively associated with the severity of coronary stenosis/occlusion (r = 0.72, P = 0.011) and with the extent of coronary thrombus (r = 0.64, P = 0.014). The concentrations of high-sensitivity C-reactive protein, however, did not differ across groups.

Conclusions: Our results demonstrate alterations in extracellular matrix biomarkers in KD patients, suggesting enhanced collagen synthesis and ameliorated degradation in adolescents and young adults late after the onset of KD. We also observed an association between the concentrations of PIIINP and the extent of coronary stenosis/occlusion or thrombosis in KD patients, a finding that needs confirmation in further studies.
Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH
Authors: Balavoine Anne-Sophie , Ladsous Miriam , Velayoudom Fritz-Line , Vlaeminck Virginie , Cardot-Bauters Catherine , d'Herbomez Michèle , Wemeau Jean-Louis
Published: September 2008

Objective

Hypothyroidism is a manifestation of multi-hormonal resistance in pseudohypoparathyroidism type Ia (PHP Ia). The objective of the study was to determine the mechanisms of hypothyroidism in PHP Ia.

Design

A prospective study.

Patients

Ten patients with PHP Ia.

Measurements

The serum concentrations of TSH, free triiodothyronine (FT3), free thyroxine (FT4), and prolactin (PRL) were measured at baseline and after stimulation with TRH (200 μg i.v).

Results

The median basal serum TSH concentration was 4.92 mU/l. Basal serum TSH concentration was slightly elevated in eight patients (4.22–7.0 mU/l; normal range, 0.4–3.6 mU/l), normal in one patient (2.5 mU/l), and high in one patient (13.1 mU/l). After the TRH test, TSH concentrations increased to 13.4–36.0 mU/l (normal range, 4.0–20.0 mU/l). The absolute values after the test were normal in three patients and high in seven patients. However, TSH responses relative to the baseline value (stimulated/basal TSH and expressed as a fold increase), which reflect the relative increases after TRH stimulation, were low in seven patients (2.3- to 4.3-fold TSH) and normal in three patients. Basal FT4 concentration was normal in seven patients and low in three patients (range, 8.4–20.0 pmol/l; mean, 14.1±4.3 pmol/l; normal range, 10.5–23.0 pmol/l). Basal FT3 concentration was normal in nine patients and low in one patient (range, 0.9–5.0 pmol/l; mean, 3.8±1.1 pmol/l; normal range, 3.3–6.1 pmol/l). FT4 and FT3 were not significantly increased after the TRH test. PRL concentration was normal at baseline and increased from 7 to 96 ng/ml after TRH.

Conclusion

Our results support the hypothesis that patients with PHP Ia have impaired sensitivity to both TSH and TRH.
A deficiency of lunatic fringe is associated with cystic dilation of the rete testis
Authors: Hahn K L , Beres B , Rowton Megan J , Skinner M K , Chang Y , Rawls A , Wilson-Rawls J
Published: September 2008

Lunatic fringebelongs to a family of β1–3N-acetyltransferases that modulate the affinity of the Notch receptors for their ligands through the elongation ofO-fucose moieties on their extracellular domain. A role for Notch signaling in vertebrate fertility has been predicted by the intricate expression of the Notch receptors and their ligands in the oocyte and granulosa cells of the ovary and the spermatozoa and Sertoli cells of the testis. It has been demonstrated that disruption of Notch signaling by inactivation of lunatic fringe led to infertility associated with pleiotropic defects in follicle development and meiotic maturation of oocytes. Lunatic fringe null males were found to be subfertile. Here, we report that gene expression data demonstrate that fringe and Notch signaling genes are expressed in the developing testis and the intratesticular ductal tract, predicting roles for this pathway during embryonic gonadogenesis and spermatogenesis. Spermatogenesis was not impaired in the majority of the lunatic fringe null males; however, spermatozoa were unilaterally absent in the epididymis of many mice. Histological and immunohistochemical analysis of these testes revealed the development of unilateral cystic dilation of the rete testis. Tracer dye experiments confirm a block in the connection between the rete testis and the efferent ducts. Further, the dye studies demonstrated that many lunatic fringe mutant males had partial blocks of the connection between the rete testis and the efferent ducts bilaterally.
Phenotypic and Functional Reversal Within the Early Human Hematopoietic Compartment
Authors: Knaän-Shanzer Shoshan , van der Velde-van Dijke Ietje , van de Watering Marloes J.M. , de Leeuw Philip J. , Valerio Dinko , van Bekkum Dirk W. , de Vries Antoine A.F.
Published: September 2008

The fate of phenotypically defined human hematopoietic stem cells (hHSCs) in culture and the link between their surface marker expression profile and function are still controversial. We studied these aspects of hHSC biology by relating the expression of the early lineage markers (ELM) CD33, CD38, and CD71 on the surface of human umbilical cord blood (UCB) CD34+ cells to their long-term nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse repopulation activity (LT-SRA). In uncultured UCB samples, LT-SRA was largely confined to the small CD34+ELM− cell fraction. CD34+ cells expressing ELM markers at their surface usually lacked LT-SRA. After culturing UCB CD34+ cells for 6 days in serum-free medium and on a feeder layer of Rat2 cells, the number of CD34+ELM− cells stayed roughly the same or showed a slight increase and the LT-SRA was preserved, suggesting a close association between LT-SRA and the CD34+ELM− phenotype. Indeed, transplantation of CD34+ELM− cells isolated from cultured UCB CD34+ cells resulted in long-term hematopoietic reconstitution of conditioned NOD/SCID mice, whereas CD34+ELM+ cells derived from the same cultures were devoid of LT-SRA. Remarkably, roughly 1% of the cells recovered from cultures initiated with isolated CD34+ELM+ cells had lost ELM surface expression. Concurrently, the cultured CD34+ELM+ cells acquired LT-SRA, suggesting that hematopoietic stem cells (HSCs) may arise by the dedifferentiation of early hematopoietic progenitor cells. The latter finding challenges the paradigm of unidirectional hematopoietic differentiation and opens new opportunities for HSC expansion prior to transplantation.

Disclosure of potential conflicts of interest is found at the end of this article.
Brain Cancer Stem Cells Display Preferential Sensitivity to Akt Inhibition
Authors: Eyler Christine E. , Foo Wen-Chi , LaFiura Katherine M. , McLendon Roger E. , Hjelmeland Anita B. , Rich Jeremy N.
Published: September 2008

Malignant brain tumors are among the most lethal cancers, and conventional therapies are largely limited to palliation. Novel therapies targeted against specific molecular pathways may offer superior efficacy and less toxicity than conventional therapies, but initial clinical trials of molecular targeted agents in brain cancer therapy have been frequently disappointing. In brain tumors and other cancers, subpopulations of tumor cells have recently been characterized by their ability to self-renew and initiate tumors. Although these cancer stem cells, or tumor initiating cells, are often only present in small numbers in human tumors, mounting evidence suggests that cancer stem cells contribute to tumor maintenance and therapeutic resistance. Thus, the development of therapies that target cancer stem cell signal transduction and biology may improve brain tumor patient survival. We now demonstrate that populations enriched for cancer stem cells are preferentially sensitive to an inhibitor of Akt, a prominent cell survival and invasion signaling node. Treatment with an Akt inhibitor more potently reduced the numbers of viable brain cancer stem cells relative to matched nonstem cancer cells associated with a preferential induction of apoptosis and a suppression of neurosphere formation. Akt inhibition also reduced the motility and invasiveness of all tumor cells but had a greater impact on cancer stem cell behaviors. Furthermore, inhibition of Akt activity in cancer stem cells increased the survival of immunocompromised mice bearing human glioma xenografts in vivo. Together, these results suggest that Akt inhibitors may function as effective anticancer stem cell therapies.

Disclosure of potential conflicts of interest is found at the end of this article.
Isolation of Primordial Germ Cells from Differentiating Human Embryonic Stem Cells
Authors: Tilgner Katarzyna , Atkinson Stuart P. , Golebiewska Anna , Stojković Miodrag , Lako Majlinda , Armstrong Lyle
Published: September 2008

Of all the cell types that can be obtained from the differentiation of embryonic stem cells, primordial germ cells are arguably the most fascinating, as they represent the in vitro completion of the reproductive cycle of the organism from which the embryonic stem cell line was derived. It is also possible to obtain these cells from embryos at an appropriate stage of development, but this process yields only small numbers that are not applicable to investigations of their epigenetic architecture. A considerable body of data has been generated from the differentiation of mouse embryonic stem cells to this cell type, but despite the demonstration of their presence in human embryoid bodies, there has been little progress toward methods of producing human primordial germ cells in useful numbers. We present here a robust protocol to differentiate two human embryonic stem cell lines (H9 and hES-NCL1) that maximizes the numbers of primordial germ cells that may be obtained using a simple fluorescence-activated cell sorting strategy for their isolation. These primordial germ cells demonstrate high-level expression of the germ cell-specific VASA gene and show removal of parental imprints and chromatin modification changes that support their primordial germ cell identity.

Disclosure of potential conflicts of interest is found at the end of this article.
Bromodeoxyuridine Induces Senescence in Neural Stem and Progenitor Cells
Authors: Ross Heather H. , Levkoff Lindsay H. , Marshall Gregory P. , Caldeira Maria , Steindler Dennis A. , Reynolds Brent A. , Laywell Eric D.
Published: September 2008

Bromodeoxyuridine (BrdU) is a halogenated pyrimidine that incorporates into newly synthesized DNA during the S phase. BrdU is used ubiquitously in cell birthdating studies and as a means of measuring the proliferative index of various cell populations. In the absence of secondary stressors, BrdU is thought to incorporate relatively benignly into replicating DNA chains. However, we report here that a single, low-dose pulse of BrdU exerts a profound and sustained antiproliferative effect in cultured murine stem and progenitor cells. This is accompanied by altered terminal differentiation, cell morphology, and protein expression consistent with the induction of senescence. There is no evidence of a significant increase in spontaneous cell death; however, cells are rendered resistant to chemically induced apoptosis. Finally, we show that a brief in vivo BrdU regimen reduces the proliferative potential of subsequently isolated subependymal zone neurosphere-forming cells. We conclude, therefore, that BrdU treatment induces a senescence pathway that causes a progressive decline in the replication of rapidly dividing stem/progenitor cells, suggesting a novel and uncharacterized effect of BrdU. This finding is significant in that BrdU-incorporating neural stem/progenitor cells and their progeny should not be expected to behave normally with respect to proliferative potential and downstream functional parameters. This effect highlights the need for caution when results based on long-term BrdU tracking over multiple rounds of replication are interpreted. Conversely, the reliable induction of senescence in stem/progenitor cells in vitro and in vivo may yield a novel platform for molecular studies designed to address multiple aspects of aging and neurogenesis.

Disclosure of potential conflicts of interest is found at the end of this article.
Regulation of Prenatal Human Retinal Neurosphere Growth and Cell Fate Potential by Retinal Pigment Epithelium and Mash1
Authors: Gamm David M. , Wright Lynda S. , Capowski Elizabeth E. , Shearer Rebecca L. , Meyer Jason S. , Kim Hyun-Jung , Schneider Bernard L. , Melvan John Nicholas , Svendsen Clive N.
Published: September 2008

During development of the central nervous system, stem and progenitor cell proliferation and differentiation are controlled by complex inter- and intracellular interactions that orchestrate the precise spatiotemporal production of particular cell types. Within the embryonic retina, progenitor cells are located adjacent to the retinal pigment epithelium (RPE), which differentiates prior to the neurosensory retina and has the capacity to secrete a multitude of growth factors. We found that secreted proteinaceous factors in human prenatal RPE conditioned medium (RPE CM) prolonged and enhanced the growth of human prenatal retinal neurospheres. The growth-promoting activity of RPE CM was mitogen-dependent and associated with an acute increase in transcription factor phosphorylation. Expanded populations of RPE CM-treated retinal neurospheres expressed numerous neurodevelopmental and eye specification genes and markers characteristic of neural and retinal progenitor cells, but gradually lost the potential to generate neurons upon differentiation. Misexpression of Mash1 restored the neurogenic potential of long-term cultures, yielding neurons with phenotypic characteristics of multiple inner retinal cell types. Thus, a novel combination of extrinsic and intrinsic factors was required to promote both progenitor cell proliferation and neuronal multipotency in human retinal neurosphere cultures. These results support a pro-proliferative and antiapoptotic role for RPE in human retinal development, reveal potential limitations of human retinal progenitor culture systems, and suggest a means for overcoming cell fate restriction in vitro.

Disclosure of potential conflicts of interest is found at the end of this article.
Quantitative Mass Spectrometry Identifies Drug Targets in Cancer Stem Cell-Containing Side Population
Authors: Steiniger Sebastian C.J. , Coppinger Judith A. , Krüger Jörg A. , Yates John , Janda Kim D.
Published: September 2008

A multifaceted approach is presented as a general strategy to identify new drug targets in a breast cancer stem cell-containing side population. The approach we have utilized combines side population cell sorting and stable isotope labeling by amino acids in cell culture with mass spectrometry to compare and identify proteins with differential expression profiles between side population cells, know to be enriched in cancer stem cells, and nonside population cells, which are depleted in cancer stem cells, for two breast cancer cell lines, MCF7 and MDA-MB231. Almost 900 proteins were quantified, and several important proteins in cell cycle control and differentiation were found to be upregulated in the cancer stem cell-containing side population. Most interestingly, a splice isoform of pyruvate kinase M2 as well as peroxiredoxin 6 were found to be downregulated. The differential levels of three of these proteins, thymosin β4 (TB4), proliferation-associated protein 2G4, and SIAH-interacting protein, were validated using Western blot. Furthermore, functional validation provided clear evidence that elevated TB4 expression contributes to drug resistance in the stem cell population. Small interfering RNA silencing of TB4 led to a loss of chemoresistance in two separate breast cancer populations. These proteins likely contribute to resistance in the cancer stem cell-containing side population, and their altered expression in a tumor causes clinical resistance to chemotherapy. The ability to perform quantitative mass spectrometry has enabled the identification of a series of proteins that could serve as future therapeutic targets.

Disclosure of potential conflicts of interest is found at the end of this article.
The Stem Cell-Associated Antigen CD133 (Prominin-1) Is a Molecular Therapeutic Target for Metastatic Melanoma
Authors: Rappa Germana , Fodstad Oystein , Lorico Aurelio
Published: September 2008

CD133 (Prominin-1) is considered the most important cancer stem cell (CSC)-associated marker identified so far, with increased expression in the CSC fraction of a large variety of human malignancies, including melanoma. Here we investigated the effects of CD133 downregulation in vitro and in vivo in human metastatic melanoma. The average number of CD133 molecules on the cell surface of FEMX-I melanoma cells was decreased by 8.7-fold and 1.8-fold using two different short hairpin RNAs. Downregulation of CD133, confirmed by immunocytochemistry, Western blotting, microarray analysis, and reverse transcription-polymerase chain reaction, resulted in slower cell growth, reduced cell motility, and decreased capacity to form spheroids under stem cell-like growth conditions. Clonal analysis revealed that the reduction in growth rate was proportional to the extent of CD133 downregulation. Monoclonal antibodies directed against two different epitopes of the CD133 protein induced a specific, dose-dependent cytotoxic effect in FEMX-I cells. The downregulation of CD133 severely reduced the capacity of the cells to metastasize, particularly to the spinal cord. In the CD133 downregulated cells, microarray analysis revealed expression changes for only 143 annotated genes (76 up- and 67 downregulated). Ten of the 76 upregulated genes coded for Wnt inhibitors, suggesting an interaction between CD133 and the canonical Wnt pathway. We conclude that CD133, in addition to its role as a CSC marker, is an important therapeutic target for metastatic melanoma and, potentially, for other CD133-expressing cancer types.

Disclosure of potential conflicts of interest is found at the end of this article.
Effect of aggregate on high-strength concrete in fire
Authors: Yan X. , Li H. , Wong Y.-L.
Published: September 2008

Aggregate is a significant factor that affects the behaviour of high-strength concrete (HSC) in fire. Herein, the during-fire damage, namely explosive spalling, of 33 HSC specimens was experimentally studied to identify the effect of aggregate on HSC in fire. Four types of aggregate including dolomite, quartzitic gravel, granite and sandstone were mixed in the concrete specimens and their design strengths were all 90 MPa. In the heating tests, the fully saturated specimens were subjected to an oven-heating condition (2°C/min) or a simulated standard fire condition (BS 476) respectively. Results indicated that there was no effect of the type of aggregate on the spalling mode of HSC in fire. However, obvious effects of various types of aggregate on the spalling degree of HSC in fire were pointed out, and subsequently a spalling self-prevention concept was introduced to explain it.
Enteroviral meningitis in children in Turkey
Authors: Şensoy Gülnar , Sel Kutay , Özkaya Ethem , Çuhaci Çakir Bahar , Vidinlisan Sadi , Doganci Levent
Published: September 2008

In the indexed medical literature, there have been a very limited number of studies to investigate the epidemiologic and clinical features of enteroviral meningitis in Turkey. The aim of the present retrospective study is to update the actual situation to recognize the spectrum and magnitude of this important clinical entity. Between June 1999 and December 2004, 612 cases of aseptic meningitis were followed up at our hospital. Enteroviral meningitis was defined by isolation of enteroviruses from cerebrospinal fluid (CSF) and/or stool samples. Mumps virus was detected in 310 cases (50.7%) and enteroviruses were the etiologic agents in 104 (17%) of the patients with aseptic meningitis. Most of the enteroviral meningitis cases (36 cases, 34.6%) were diagnosed in August and 70 (67.3%) of them were male. The mean age was 5.6 ± 3.4 years. The most common initial symptoms were fever (81.7%), vomiting (77.9%) and headache (57.7%). In the physical examination, 46.2% of the cases had neck stiffness and 38.5% had pharyngitis. Echovirus 30 was the most frequently (38 cases, 36.5%) isolated enterovirus with peaks in 1999, 2002 and 2004. The other frequently isolated enteroviruses were Coxsackie virus type B (17 cases, 16.3%), echovirus 6 (11 cases, 10.6%), echovirus 11 (6 cases, 5.8%), and echovirus 13 (4 cases, 3.8 %). Mean hospitalization time was 6.2 ± 2.4 days. All patients recovered without any sequelae. Enteroviruses have an important role in childhood aseptic meningitis cases in Turkey too, and the predominant serotypes vary according to years.
Effect of Weight-Bearing Activity on Foot Ulcer Incidence in People With Diabetic Peripheral Neuropathy: Feet First Randomized Controlled Trial
Authors: LeMaster Joseph W , Mueller Michael J , Reiber Gayle E , Mehr David R , Madsen Richard W , Conn Vicki S
Published: September 2008

Background

Weight-bearing exercise has been contraindicated among people with diabetic peripheral neuropathy (DM+PN). However, recent cohort studies have suggested that daily weight-bearing activity is associated with lower risk for foot ulceration.

Objective

The objective of this study was to determine the effect of a lower-extremity exercise and walking intervention program on weight-bearing activity and foot ulcer incidence in people with DM+PN.

Design

This was an observer-blinded, 12-month randomized controlled trial.

Setting

The settings were physical therapy offices in part 1 of the intervention and the community in part 2 of the intervention.

Participants

The participants were 79 individuals with DM+PN who were randomly assigned either to a control group (n=38) or an intervention group (n=41) group.

Intervention

Intervention components included leg strengthening and balance exercises; a graduated, self-monitored walking program (part 1); and motivational telephone calls every 2 weeks (part 2). Both groups received diabetic foot care education, regular foot care, and 8 sessions with a physical therapist.

Measurements

Total and exercise bout–related daily steps at baseline and at 3, 6, and 12 months were measured by accelerometers. Foot lesions/ulcers were photographed and classified by an independent panel of dermatologists. Use of adequate footwear was monitored.

Results

At 6 months, bout-related daily steps increased 14% from baseline in the intervention group and decreased 6% from baseline in the control group. Although the groups did not differ statistically in the change in total daily steps, at 12 months steps had decreased by 13% in the control group. Foot ulcer rates did not differ significantly between groups.

Conclusion

Promoting weight-bearing activity did not lead to significant increases in foot ulcers. Weight-bearing activity can be considered following adequate assessment and counseling of patients with DM+PN.
Physical Activity and Diabetes: Opportunities for Prevention Through Policy
Authors: Deshpande Anjali D , Dodson Elizabeth A , Gorman Ira , Brownson Ross C
Published: September 2008

Over the past decade, the prevalence of type 2 diabetes mellitus has reached epidemic levels in the United States and other developed countries. With a concomitant rise in obesity levels in the United States and advances in the treatment of diabetes and its complications, the prevalence of diabetes is expected to continue to rise through the year 2050. Despite strong evidence that regular physical activity can prevent or delay the onset of diabetes, too many Americans are not meeting the recommended levels of regular physical activity. Although most physical activity interventions to date have been focused on characteristics of the individual, more-recent studies have considered how changing characteristics of the social and physical environment in which people live may ultimately have a greater impact on increasing population levels of physical activity. Policy interventions are a way to make sustainable changes in the physical environment of a community and thus provide support for other intrapersonal and interpersonal behavioral change interventions. Policy changes also can affect the social norms that shape behavior. The purposes of this perspective article are: (1) to describe the rationale for population approaches to primary prevention of type 2 diabetes, (2) to discuss how policy interventions can increase physical activity levels within populations, and (3) to provide recommendations for the role of physical therapists in interventions that can increase the level of physical activity in communities. Public health approaches to curb the diabetes epidemic are urgently needed. Policy interventions to increase population levels of physical activity show promise for diabetes prevention. Physical therapists are uniquely suited to influence primary prevention efforts for diabetes.
Intricacies of Fat
Authors: Stehno-Bittel Lisa
Published: September 2008

One of the most exciting cell biology fields of study concerns the physiology and pathology of fat. The basic assumptions once held concerning the function of adipose tissue have been shown to be oversimplified or sometimes completely wrong. Fat does more than store excess energy; it is actually the largest endocrine organ in the body, and it may be one of the most active. Adipocytes release hormones and other molecules that act on nearby tissues and travel through the vasculature to distant sites, such as the brain, skeletal muscle, and liver. Under conditions of normal weight, those signals help the body to suppress hunger, utilize glucose, and decrease the risk of cardiovascular disease. However, under conditions of obesity, the hormones (or the proteins that bind the hormones) become abnormal and can result in states of chronic inflammation leading to diabetes and heart disease. In addition, excessive fat can lead to the accumulation of lipid droplets in nonfat cells, including skeletal and cardiac muscle. Although some lipid droplets are used as an immediate source of energy for cells, large numbers of stored droplets can cause cellular damage and cell death. The purposes of this article are to review the normal and deviant signals released by fat cells, to draw a link between those signals and chronic diseases such as diabetes, and to discuss the role of exercise in reversing some of the deviant signaling perpetrated by excess fat.
Excessive Adipose Tissue Infiltration in Skeletal Muscle in Individuals With Obesity, Diabetes Mellitus, and Peripheral Neuropathy: Association With Performance and Function
Authors: Hilton Tiffany N , Tuttle Lori J , Bohnert Kathryn L , Mueller Michael J , Sinacore David R
Published: September 2008

Background and Purpose

The primary purpose of this study was to report differences in calf intermuscular adipose tissue (IMAT), muscle strength (peak torque), power, and physical function in individuals with obesity, diabetes mellitus (DM), and peripheral neuropathy (PN) compared with those without these impairments. A secondary purpose was to assess the relationship between IMAT and muscle strength, power, and physical function.

Subjects and Methods

Six participants with obesity, DM, and PN (2 women, 4 men; mean age=58 years, SD=10; mean body mass index=36.3, SD=5; mean modified Physical Performance Test [PPT] score=22, SD=3) and 6 age- and sex-matched control subjects without these impairments were assessed and compared in muscle strength, muscle power, physical functioning, and muscle and fat volume, including IMAT in the calf muscles. Muscle, adipose tissue, and IMAT volumes of each calf were quantified by noninvasive magnetic resonance imaging. Muscle strength and power of the plantar-flexor and dorsiflexor muscles were quantified using isokinetic dynamometry. The modified PPT was used to assess physical function.

Results

Leg muscle and fat volumes were similar between groups, although IMAT volumes were 2.2-fold higher in the subjects with obesity, DM, and PN (X̅=120 cm3, SD=47) than in the control subjects (X̅=54 cm3, SD=41). Muscle strength, muscle power, ratio of leg muscle power to leg muscle volume, and modified PPT scores were lower in subjects with obesity, DM, and PN compared with the control subjects.

Discussion and Conclusion

The data indicate that excess fat infiltration in leg skeletal muscles is associated with low calf muscle strength, low calf muscle power, and impaired physical function in individuals who are obese with DM and PN.
The Influence of Culture on Negotiati on Styles of Brazilian Executives
Authors: Sobral Filipe , Carvalhal Eugenio , Almeida Filipe
Published: September 2008

Culture profoundly influences how people think, communicate, and behave. Successful cross‐cultural negotiations require an understanding of the negotiation style of those on the other side of the table, and the acceptance and respect of their cultural beliefs and norms. The focus of this paper is to identify the styles of negotiation that tend to be adopted by Brazilian negotiators. Participants were 683 experienced negotiators from 22 Brazilian states. The Brazilian style of negotiation is described based on seven culturally sensitive dimensions that are present in negotiations: the nature of the activity, the role of the individual, uncertainty and time, communication, trust, protocol, and outcomes.
Qualitative Study of Novice Physical Therapists' Experiences in Private Practice
Authors: Solomon Patricia , Miller Patricia A.
Published: September 2008

Purpose: The purpose of this study was to gain insight into the experiences of novice physiotherapists whose initial employment was in private practice and to gain an understanding of how they adapted to their new role.

Methods: Using a qualitative grounded theory approach, 10 novice physiotherapists employed in private practice participated in a semistructured telephone interview. Transcribed interviews were analyzed through an open coding technique. Seven thematic areas emerged from the data.

Results: The novice physiotherapists experienced feelings of stress and insecurity during the transition from student to practitioner. Dealing with issues related to insurance patients and with challenging patients contributed to their feelings of being overwhelmed. Supportive environments with other physiotherapists willing to be role models and mentors assisted in allowing the novices to learn and quickly adapt to their new professional role.

Conclusions: Employers, educators, and colleagues can use strategies to promote a successful transition from student to practitioner by novice physiotherapists whose initial work experience is in private practice.
The Flutter Device versus the PEP Mask in the Treatment of Adults with Cystic Fibrosis
Authors: Newbold M. Ellen , Tullis Elizabeth , Corey Mary , Ross Brenda , Brooks Dina
Published: September 2008

Purpose: The purpose of this study was to compare the effectiveness of the Flutter device (Axcan Scandipharm Inc., Birmingham, AL) with that of the PEP Mask (Astra Tech AB, Molndal, Sweden) in the treatment of adults with cystic fibrosis (CF).

Methods: Forty-two adults (mean age 29 F 8.4 years) were recruited from the Adult Cystic Fibrosis Program at St. Michael's Hospital and were randomly assigned to airway clearance treatment with either the Flutter device or the PEP Mask. Pulmonary function tests, the Quality of Well-Being Scale (QWB), and the Chronic Respiratory Disease Questionnaire (CRQ) were administered 1 month postrecruitment and every 3 months thereafter for 13 months.

Results: Using linear regression, the mean slope or annual rate of change of forced expiratory volume in 1 second (FEV1) percent predicted was 2.0 (F 8.1) for the Flutter group and 4.2 (F 8.0) for the PEP group (p=.4). There were no significant between-group differences in the slopes of the QWB (p=.3) or CRQ (p = 1.0) total scores. The power to detect differences was low (0.137).

Conclusions: When comparing the Flutter device and the PEP Mask in the treatment of adults with CF over a 13-month period, there were no significant differences in pulmonary function or health-related quality of life. A much larger sample would be needed to conclude with confidence that there were no between-group differences. Therefore, additional research is needed to further examine the effectiveness of the Flutter device and the PEP Mask.
13-Metre Walk Test Applied to the Elderly with Musculoskeletal Impairment: Validity Study
Authors: Mori Brenda , Lundon Katie , Kreder Hans J.
Published: September 2008

Purpose: The purpose of this study was to examine concurrent validity and known group validity for the 13-metre walk test.

Methods: Preoperative data were collected from a sample of elderly individuals awaiting total hip replacement. The measures used were the Timed Up & Go Test, 13-metre walk test, 6-minute walk test, Stair Performance Measure, and the three subscales from the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results: Scores on the 13-metre walk test were significantly correlated with each of the other functional outcome measures, although the magnitude of the correlations with the WOMAC subscales was modest. Subjects performed the 13-metre walk test at a greater velocity than the 6-minute walk test (p < .01). Individuals with gait aids performed more poorly than those without (p < .01).

Conclusions: The findings of this study support concurrent validity and known group validity for the 13-metre walk test. Information regarding additional psychometric characteristics, that is, the interrater and intrarater reliability and responsiveness of the 13-metre walk test, would be valuable to further support its use.