bluuebunny/crossref_metadata_2025 huggingface dataset:
Clustered binary data with random cluster sizes
Authors: Ma Renjun , Jørgensen Bent , Willms Jon Douglas
Published: July 2009

In the analysis of clustered binary data with random cluster sizes, traditional approaches assuming fixed cluster sizes are generally used. Appropriate inference should take account of both intra-cluster correlation and extra-variation arising from the random cluster sizes. We introduce a dual Poisson random effects model for performing appropriate analyses of such data. Our orthodox best linear unbiased predictor approach to this model depends only on the first- and second- moment assumptions of unobserved random effects. This approach is illustrated with analyses of seed germination data and developmental toxicity data.
Extended truncated Inverse Gaussian–Poisson model
Authors: Puig Xavier , Ginebra Josep , Perez-Casany Marta
Published: July 2009

The inverse Gaussian–Poisson mixture model is very useful when modelling highly skewed non-negative integer data in fields as diverse as linguistics, ecology, market research, bibliometry, engineering and insurance. When using this statistical model on the frequency of word or species frequency data, one typically truncates its sample space at zero to accommodate for the ignorance about the number of words or species that are not observed. In this paper, we show that by truncating the sample space of the inverse Gaussian–Poisson model, one is allowed to extend its parameter space and in that way improve its fit when the frequency of one is larger and the right tail is heavier than is allowed by the unextended model. By fitting the extended model to word frequency count data, we find many instances where the maximum likelihood estimates fall in the extension of the parameter space.
Typologies of Young Resisters and Desisters
Authors: Murray Cathy
Published: July 2009

The Quest for Identitystudy explores how young people maintain their resistance to offending and it argues that for some this entails active resistance, rather than merely reflecting an innocence often associated with childhood non-offending. Two qualitative methods were used in the study to elicit young people's own perspectives. Secondary analysis was conducted on 112 semi-structured interviews with teenagers, 62 of whom who had never offended (`resisters') and 50 of whom had offended and then ceased (`desisters'). Additionally, primary data were gathered by means of peer led focus groups conducted with 52 resisters. A key contribution of the study is the development of typologies of young resisters and desisters. The article outlines the two resister types, namely innocentsand streetwise resistersand the three desister types: reformed characters, desisters on the margins, and quasi-resisters(desisters who retain a resister identity) which were developed during the analysis. It also considers the implications of the findings for policy, practice and research.
Transfer of Juvenile Offenders to Adult Court in Belgium: Critical Reflections on the Reform of a Moderate Practice
Authors: Christiaens Jenneke , Nuytiens An
Published: July 2009

Several Western European juvenile justice systems have become more punitive in the last few decades. This article explores whether the Belgian juvenile justice system, traditionally one of the most welfare oriented in Europe, has taken a punitive turn as well. An analysis of the recent amendment of the most punitive element in the Belgian juvenile justice system, transfer to Adult Court, does not provide a definite answer. The regulations on transfer were not made harsher by the new Youth Act. However, we will argue that the amendment, although `mild' at first sight, may, in practice, result in a punitive shift.
Exploring Knowledge Sharing in Social Structures: Potential Contributions to an Overall Knowledge Management Strategy
Authors: Blankenship Selena S. , Ruona Wendy E. A.
Published: July 2009

The problem and the solution. As more attention has turned to knowledge management in organizations, there has been an increasing shift in focus from technology solutions to social dimensions. It is the focus on people and the management of knowledge-sharing processes that has lacked attention in the literature and is of particular importance to the HRD profession. Knowledge sharing has been identified as the most critical factor in knowledge management, yet we do not fully understand how individuals share knowledge or the role social structures such as teams and work-related communities could play in an overall knowledge management strategy. Through a review of the literature, the authors explore types of social structures in organizations and the knowledge shared within these structures. From this review, they suggest potential new ways of thinking about the role of HRD in the design of social structures and the facilitation of knowledge-sharing processes.
Holistic Views of Knowledge Management Models
Authors: Baiyin Yang  , Wei Zheng  , Viere Chris
Published: July 2009

The problem and the solution. Based on a newly developed holistic theory of knowledge and learning, this article critically evaluates selected models of knowledge management (KM) and proposes a holistic KM model. Most existing KM models tend to narrowly define knowledge from conceptual and perceptual perspectives and fail to recognize affectual knowledge such as values and visions. Furthermore, most models view KM as a linear or cyclical process and thus fail to identify the multidimensional nature of the knowledge dynamics between individuals and organizations. Implications of the holistic model for human resource development are discussed.
A Case Study on Knowledge Management of Busan Metropolitan City
Authors: Ahn Youngsik , Park Suhong , Jung Juyoung
Published: July 2009

The problem and the solution. Knowledge is a pivotal engine for organizational growth. Knowledge management can be used by an organization to develop human resources to gain a competitive edge in the market.This article identifies cases of knowledge management in the public sector, which is relatively little researched compared with the private sector. In particular, the case study of Busan Metropolitan City encompasses information technology, organizational culture, and human resource development. In addition, this article explores strategies for improving knowledge management practices in Busan.
Knowledge Management Initiatives, Organizational Process Alignment, Social Capital, and Dynamic Capabilities
Authors: Hung Richard Yu-Yuan , Lien Bella Ya-Hui , McLean Gary N.
Published: July 2009

The problem and the solution. Organizations that create their own dynamic capabilities are better able to sustain competitive advantage. Organizational dynamic capabilities are abilities to integrate, build, and reconfigure internal and external competencies to address rapidly changing environments. Knowledge management initiatives can play an important role to help integrate organizational resources, align organizational business processes, rebuild organizational learning culture, and strengthen organizational social capital. This article includes the following themes: (a) knowledge management and dynamic capabilities are intertwined; (b) through knowledge management, effective organizational process alignment can enhance dynamic capabilities; and (c) knowledge management and social capital influence each other and, further, both strengthen dynamic capabilities.
The Use of Illustrated Story Mapping to Enhance Focus Group Discussion
Authors: Ureda John R. , Byrd Theresa L. , Calderón-Mora Jessica A. , Casillas Myriam E. , Williams Deloris G. , Scott Dolores B.
Published: July 2009

Key informant interviews and focus groups assist in eliciting qualitative data from the community in order to develop educational programs. This article describes how an additional methodology, illustrated story maps, are used to obtain context-specific information on what African American and Hispanic men need to know to make an informed decision about prostate cancer screening. These maps are created as a result of key informant interviews and implemented during focus groups. Twenty focus groups are conducted using the story maps, which depicts scenarios of how men make medical decisions, possible influences on medical decisions, and potential consequences of these decisions. The illustrated story maps prove to encourage directed discussion during the focus groups, while still allowing for open sharing of personal experiences. The authors recommend the use of maps when adapting and planning communication and educational programs, particularly where participant dialogue is central to success of the endeavor.
Posttraumatic Pseudoaneurysm of the Temporal Artery
Authors: McDowell Jennifer Anne
Published: July 2009

This is a case presentation of a pediatric patient with severe head trauma resulting from a motor vehicle accident. The patient had been hospitalized for approximately two weeks prior to a request to review a pulsatile mass that had developed after trauma with sonography. Sonographic imaging showed an enlarged vessel with mixed echos throughout. The diagnosis by sonography with duplex confirmed the pulsatile lesion to be a pseudoaneurysm of the temporal artery with mural thrombus.
TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas
Authors: Honma Keiichiro , Tsuzuki Shinobu , Nakagawa Masao , Tagawa Hiroyuki , Nakamura Shigeo , Morishima Yasuo , Seto Masao
Published: July 2009

The constitutive activation of nuclear factor-κB (NF-κB) has been implicated in tumorigenesis of lymphoid malignancies. We have previously shown that chromosome 6q was frequently deleted in ocular marginal zone B-cell lymphoma and identified TNFAIP3/A20, a negative regulator of NF-κB pathways, as the primary target for 6q deletion. In the study reported here, we extended the analysis to other subsets of non-Hodgkin lymphomas and found that A20 is frequently deleted in mantle cell lymphoma and diffuse large B-cell lymphoma. Importantly, A20 promoter methylation or gene mutation is also frequently detected in these lymphomas, raising the possibility that inactivation of A20 may be involved in lymphomagenesis. To address this question, we conducted overexpression experiments in lymphoma cell lines with A20 deletion and down-regulated expression of A20 with an siRNA technique in Epstein-Barr virus–infected lymphoblastoid cell lines. These experiments found that overexpression of A20 induced apoptosis and silencing of A20 was associated with resistance to apoptosis and enhanced clonogenicity. The cells with down-regulated A20 exhibited enhanced NF-κB activities, which may account for the observed effects. These results indicate that our study provides a novel insight into molecular mechanisms leading to lymphoma and that specific targeting of NF-κB pathways may be advantageous for treatment.
Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice
Authors: Chitu Violeta , Ferguson Polly J. , de Bruijn Rosalie , Schlueter Annette J. , Ochoa Luis A. , Waldschmidt Thomas J. , Yeung Yee-Guide , Stanley E. Richard
Published: July 2009

The mouse Lupo (I282N) mutation in proline-serine-threonine phosphatase–interacting protein 2 (PSTPIP2) leads to reduced expression of PSTPIP2 that is associated with a macrophage-mediated autoinflammatory disease. Another mutation in PSTPIP2, L98P, termed chronic multifocal osteomyelits (cmo), leads to a disease in mice that resembles chronic recurrent multifocal osteomyelits in humans. The cellular basis of cmo disease was investigated. cmo disease develops independently of lymphocytes and is cured by bone marrow transplantation. Macrophages, mast cells, and osteoclasts from cmo mice fail to express detectable PSTPIP2 protein. Asymptomatic Pstpip2cmo/cmo mice have increased circulating levels of macrophage inflammatory protein 1-α and interleukin-6, and their macrophages exhibit increased production of these inflammatory mediators, which is normalized by retroviral expression of wild-type PSTPIP2. Spleens of asymptomatic cmo mice contain increased numbers of macrophage precursors, and cmo mice mobilize more macrophage precursors in response to a sterile inflammatory stimulus. Signal transducer and activator of transcription 1 is elevated in cmo splenic macrophages, which also exhibit increased colony-stimulating factor-1–stimulated proliferation and increased extracellular signal-regulated kinase 1/2 phosphorylation. PSTPIP2 overexpression in macrophages leads to the opposite phenotype. Thus, PSTPIP2 deficiency causes both an expansion of macrophage progenitors and increased responsiveness of mature macrophages to activating stimuli, which together prime the organism for exaggerated and sustained responses leading to autoinflammatory disease.
Donor, recipient, and transplant characteristics as risk factors after unrelated donor PBSC transplantation: beneficial effects of higher CD34+ cell dose
Authors: Pulsipher Michael A. , Chitphakdithai Pintip , Logan Brent R. , Leitman Susan F. , Anderlini Paolo , Klein John P. , Horowitz Mary M. , Miller John P. , King Roberta J. , Confer Dennis L.
Published: July 2009

We report outcomes of 932 recipients of unrelated donor peripheral blood stem cell hematopoietic cell transplantation (URD-PBSC HCT) for acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome enrolled on a prospective National Marrow Donor Program trial from 1999 through 2003. Preparative regimens included myeloablative (MA; N = 611), reduced-intensity (RI; N = 160), and nonmyeloablative (NMA; N = 161). For MA recipients, CD34+ counts greater than 3.8 × 106/kg improved neutrophil and platelet engraftment, whereas improved overall survival (OS) and reduced transplant-related mortality (TRM) were seen for all preparative regimens when CD34+ cell doses exceeded 4.5 × 106/kg. Higher infused doses of CD34+ cell dose did not result in increased rates of either acute or chronic graft-versus-host disease (GVHD). Three-year OS and disease-free survival (DFS) of recipients of MA, RI, and NMA approaches were similar (33%, 35%, and 32% OS; 33%, 30%, and 29% DFS, respectively). In summary, recipients of URD-PBSC HCT receiving preparative regimens differing in intensity experienced similar survival. Higher CD34+ cell doses resulted in more rapid engraftment, less TRM, and better 3-year OS (39% versus 25%, MA, P = .004; 38% versus 21% RI/NMA, P = .004) but did not increase the risk of GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00785525.
The role of chemokine receptors in acute lung allograft rejection
Authors: Geleff S. , Draganovici D. , Jaksch P. , Segerer S.
Published: July 2009

Recruitment of inflammatory cells to vascularised allografts is a hallmark of rejection, and paves the way for chronic allograft injury. Chemokines play pivotal roles in the directed movement of leukocytes. Herein, we define the distribution of chemokine receptors for the most common cell types during human lung allograft rejection as a prerequisite for therapeutic interventions.

Immunohistochemistry was performed on lung allograft biopsies from 54 patients for the chemokine receptors CCR5, CXCR3 and CXCR1 and the Duffy antigen/receptor for chemokines (DARC).

Perivascular infiltrates in acute lung rejection are composed of subsets of mononuclear cells expressing the chemokine receptors CXCR1, CXCR3 and CCR5. DARC-positive small vessels and capillary vessels were associated with sites of inflammation and their number was increased during episodes of acute lung rejection. DARC expression correlated with an increase in interstitial CCR5-positive T-cells and CXCR1-positive leukocytes. Leucokytic infiltrates in bronchial/bronchiolar rejection express CXCR1 and CXCR3.

This is the first study that demonstrates an induction of the chemokine binding protein DARC at sites of acute human lung allograft rejection. Co-localisation with the chemokine receptors CXCR1 and CCR5 may indicate a role for DARC expression during leukocyte adhesion and interstitial infiltration.
Relationship of immunodiagnostic assays for tuberculosis and numbers of circulating CD4+ T-cells in HIV infection
Authors: Leidl L. , Mayanja-Kizza H. , Sotgiu G. , Baseke J. , Ernst M. , Hirsch C. , Goletti D. , Toossi Z. , Lange C.
Published: July 2009

Infection with HIV is the greatest risk factor for tuberculosis (TB) in Africa. Tuberculin skin test (TST), QuantiFERON-TB Gold In-Tube (QFT-G-IT) and T-Spot.TB assays were performed in newly diagnosed HIV-infected individuals with and without active TB and in HIV-uninfected subjects at a university outpatient clinic in Kampala, Uganda.

A total of 135 individuals were enrolled: 109 with a new diagnosis of HIV-1 infection but no active TB, 19 with HIV-1 infection and active TB, and seven HIV-uninfected healthy subjects. In control subjects immune responses were positive in 57.2% by TST and in 100% by at least one interferon-γ release assay.

In HIV-1 infected patients without active TB, induration in the TST (mm) (rho = 0.41, p-value <0.0001) and concentration of interferon (IFN)-γ in the QFT-G-IT tube withMycobacterium tuberculosis-specific antigens (rho = 0.38; p = 0.0001) were negatively correlated to numbers of circulating CD4+ T-cells, while numbers of IFN-γ producing cells (rho = 0.03–0.13; p-value = 0.21–0.77) and frequencies of positive test results for the T-Spot.TB test among groups of patients with different levels of immunodeficiency remained constant (p-value = 0.46).

In HIV-1 infection, TST and QFT-G-IT immune responses are both strongly related to the degree of immunodeficiency, while results of the T-Spot.TB are independent of the level of CD4+ T-cell depletion.
A randomised controlled trial of nasal continuous positive airway pressure on insulin sensitivity in obstructive sleep apnoea
Authors: Lam J. C. M. , Lam B. , Yao T. J. , Lai A. Y. K. , Ooi C. G. , Tam S. , Lam K. S. L. , Ip M. S. M.
Published: July 2009

The effects of treatment of obstructive sleep apnoea (OSA) on glucose metabolism have been investigated previously with conflicting results. This study evaluated the impact of nasal continuous positive airway pressure (nCPAP) treatment of OSA on insulin sensitivity.

Males with moderate/severe OSA and no significant comorbidity were randomised to a therapeutic or sham nCPAP treatment group for 1 week and then reassessed. Those who received therapeutic nCPAP were further evaluated at 12 weeks. Insulin sensitivity (Kitt) was estimated by the short insulin tolerance test. Other evaluations included blood pressure, metabolic profile, urinary catecholamines and intra-abdominal fat.

In total, 61 Chinese subjects were randomised. 31 subjects receiving therapeutic nCPAP showed an increase in Kitt(6.6±2.9 to 7.6±3.2 %·min−1; p = 0.017), while the 30 patients on sham CPAP had no significant change, and the changes in Kittwere different between the two groups (p = 0.022). At 12 weeks, improvement in Kittwas seen in 20 subjects with BMI ≥25 kg·m−2(median (interquartile range) 28.3 (26.6–31.5); p = 0.044), but not in the nine subjects with BMI<25 kg·m−2, or the entire group.

The findings indicate that therapeutic nCPAP treatment of OSA for 1 week improved insulin sensitivity in nondiabetic males, and the improvement appeared to be maintained after 12 weeks of treatment in those with moderate obesity.
The impact of time on the systemic inflammatory response in pneumococcal pneumonia
Authors: Calbo E. , Alsina M. , Rodríguez-Carballeira M. , Lite J. , Garau J.
Published: July 2009

The aim of our study was to analyse the impact of time from onset of symptoms on the systemic cytokine concentrations in patients with pneumococcal pneumonia.

Adults with severe pneumococcal pneumonia were prospectively included. At admission, vital signs, time from onset of pneumonia symptoms and circulating levels of C-reactive protein (CRP), serum amyloid A (SAA), tumour necrosis factor (TNF)-α, and interleukin (IL)-1β, IL-6, IL-8, IL-10 and IL-1ra were recorded.

32 patients were included; 13 patients had <48 h of evolution and 19 patients had been sick for >48 h. The group with a longer time of evolution presented higher plasmatic levels of TNF-α (19.1±8.5versus35.5±26 pg·mL−1), fibrinogen (6±1.8versus9±2); CRP (130±85versus327±131) and SAA (678±509versus984±391). Concentrations of TNF-α were associated with the presence of bacteraemia, initial blood pressure <90 mmHg and with a lower oxygen saturation at admission. Likewise, TNF-α levels were correlated with concentrations of IL-1β (r = 0.49), IL-6 (r = 0.41) and IL-8 (r = 0.40).

In pneumococcal pneumonia, patients with a longer time of evolution presented with higher levels of pro-inflammatory cytokines and a higher expression of acute phase proteins, suggesting a sustained release of pneumococcal antigens over time.
Rituximab-induced lung disease: a systematic literature review
Authors: Lioté H. , Lioté F. , Séroussi B. , Mayaud C. , Cadranel J.
Published: July 2009

The anti-CD20 antibody rituximab has been reported to induce a heterogeneous spectrum of lung disorders. The aim of the present study was to critically review data on the clinical presentations, causality assessments and management strategies of lung diseases possibly related to rituximab.

A systematic literature review was performed on English-language reports in PubMed until September 2008.

Cases of lung diseases ascribed to rituximab (n = 45) were identified, with three time-to-onset patterns. The most common presentation was acute/subacute hypoxaemic organising pneumonia (n = 37), starting 2 weeks after the last infusion (often around the fourth cycle) and resolving, in most cases, provided glucocorticoid therapy was given early. Acute respiratory distress syndrome occurred in five patients, within a few hours and usually after the first infusion. In the remaining three patients, macronodular organising pneumonia developed insidiously long after rituximab therapy and responded to steroids. Eight patients died. Based on time to onset, symptoms, and responses to discontinuation and rechallenge with rituximab and other drugs, 13 cases were highly compatible and 32 compatible with rituximab-induced lung disease.

Knowledge of these presentations of rituximab-induced lung disease should prove helpful for diagnosis and causality assessment purposes. Time-to-onset data, suggesting different pathogenic mechanisms, support closer clinical and perhaps radiological monitoring between infusions, particularly in patients with a history of reversible respiratory symptoms.
Genetic association study ofCYP1A1polymorphisms identifies risk haplotypes in nonsmall cell lung cancer
Authors: Wright C. M. , Larsen J. E. , Colosimo M. L. , Barr J. J. , Chen L. , McLachlan R. E. , Yang I. A. , Bowman R. V. , Fong K. M.
Published: July 2009

Lung cancer remains a leading cause of disease globally, with smoking being the largest single cause. Phase I enzymes, including cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), are involved in the activation of carcinogens, such as polycyclic aromatic hydrocarbons, to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of the present study was to investigate the association ofCYP1A1gene polymorphisms and haplotypes with lung cancer risk.

A case–control study was carried out on 1,040 nonsmall cell lung cancer (NSCLC) cases and 784 controls to investigate threeCYP1A1variants,CYP1A1*2A(rs4646903; thymidine to cytosine substitution at nucleotide 3801 (3801T>C)),CYP1A1*2C(rs1048943; 2455A>G; substitution of isoleucine 462 with valine (exon 7)) andCYP1A1*4(rs1799814; 2453C>A; substitution of threonine 461 with asparagine (exon 7)) using PCR restriction fragment length polymorphism methods.

TheCYP1A1*2AandCYP1A1*2Cvariants were significantly over-represented in NSCLC cases compared with controls, whereas theCYP1A1*4variant was under-represented.CYP1A1haplotypes (in allele orderCYP1A1*4, CYP1A1*2C, CYP1A1*2A) CGC and CGT were associated with an increased risk of lung cancer, whereas AAT was associated with decreased lung cancer risk in this population.

The present study has identified risk haplotypes forCYP1A1in NSCLC and confirmed thatCYP1A1polymorphisms are a minor risk factor for NSCLC.
A novel Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) grafted Polyethyleneimine(PCFC-g-PEI), Part 1, synthesis, cytotoxicity, and in vitro transfection study
Authors: Shi Shuai , Guo QingFa , Kan Bing , Fu ShaoZhi , Wang XiuHong , Gong ChangYang , Deng HongXin , Luo Feng , Zhao Xia , Wei YuQuan , Qian ZhiYong
Published: July 2009

Background

Polyethyleneimine (PEI), a cationic polymer, is one of the successful and widely used vectors for non-viral gene transfection in vitro. However, its in vivo application was greatly limited due to its high cytotoxicity and short duration of gene expression. To improve its biocompatibility and transfection efficiency, PEI has been modified with PEG, folic acid, and chloroquine in order to improve biocompatibility and enhance targeting.

Results

Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) (PCFC) was synthesized by ring-opening polymerization, and PCFC-g-PEI was obtained by Michael addition reaction with GMA-PCFC-GMA and polyethyleneimine (PEI, 25 kD). The prepared PCFC-g-PEI was characterized by 1H-NMR, SEC-MALLS. Meanwhile, DNA condensation, DNase I protection, the particle size and zeta potential of PCFC-g-PEI/DNA complexes were also determined. According to the results of flow cytometry and MTT assay, the synthesized PCFC-g-PEI, with considerable transfection efficiency, had obviously lower cytotoxicity against 293 T and A549 cell lines compared with that of PEI 25 kD.

Conclusion

The cytotoxicity and in vitro transfection study indicated that PCFC-g-PEI copolymer prepared in this paper was a novel gene delivery system with lower cytotoxicity and considerable transfection efficiency compared with commercial PEI (25 kD).
Identification of circulating tumour cells in early stage breast cancer patients using multi marker immunobead RT-PCR
Authors: Raynor Michael P , Stephenson Sally-Anne , Pittman Kenneth B , Walsh David CA , Henderson Michael A , Dobrovic Alexander
Published: July 2009

Introduction

The ability to screen blood of early stage operable breast cancer patients for circulating tumour cells is of potential importance for identifying patients at risk of developing distant relapse. We present the results of a study of the efficacy of the immunobead RT-PCR method in identifying patients with circulating tumour cells.

Results

Immunomagnetic enrichment of circulating tumour cells followed by RT-PCR (immunobead RT-PCR) with a panel of five epithelial specific markers (ELF3, EPHB4, EGFR, MGB1 and TACSTD1) was used to screen for circulating tumour cells in the peripheral blood of 56 breast cancer patients.

Twenty patients were positive for two or more RT-PCR markers, including seven patients who were node negative by conventional techniques. Significant increases in the frequency of marker positivity was seen in lymph node positive patients, in patients with high grade tumours and in patients with lymphovascular invasion. A strong trend towards improved disease free survival was seen for marker negative patients although it did not reach significance (p = 0.08).

Conclusion

Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients.
17β-Estradiol at Low Concentrations Acts through Distinct Pathways in Normal Versus Benign Prostatic Hyperplasia-Derived Prostate Stromal Cells
Authors: Park Irwin I. , Zhang Qiang , Liu Victoria , Kozlowski James M. , Zhang Ju , Lee Chung
Published: July 2009

The aim of this study was to identify differential responses to low concentrations of 17β-estradiol (E2) in primary stromal cell cultures derived from either normal organ donors or benign prostatic hyperplasia or hypertrophy (BPH) specimens. Furthermore, we sought to identify the potential mechanism of E2 action in these cell types, through either a genomic or nongenomic mechanism. We initially treated stromal cells derived from five normal prostates or five BPH specimens with low concentrations of E2 (0.001–1.0 nm) and analyzed their growth response. To determine whether genomic or nongenomic pathways were involved, we performed studies using specific estrogen receptor antagonists to confirm transcriptional activity or MAPK inhibitors to confirm the involvement of rapid signaling. Results of these studies revealed a fundamental difference in the mechanism of the response to E2. In normal cells, we found that a nongenomic, rapid E2 signaling pathway is predominantly involved, mediated by G protein-coupled receptor-30 and the subsequent activation of ERK1/2. In BPH-derived prostate stromal cells, a genomic pathway is predominantly involved because the addition of ICI 182780 was sufficient to abrogate any estrogenic effects. In conclusion, prostate stromal cells respond to far lower concentrations of E2 than previously recognized or examined, and this response is mediated through two distinct mechanisms, depending on its origin. This may provide the basis for new insights into the causes of, and possible treatments for, BPH.
An Adiponectin-Like Molecule with Antidiabetic Properties
Authors: Sulpice Thierry , Prunet-Marcassus Bénédicte , Molveaux Cécile , Cani Patrice D. , Vitte Pierre-Alain , Graber Pierre , Dreano Michel , Burcelin Rémy
Published: July 2009

Adiponectin increases glucose transport, reduces inflammation, and controls vascular functions. Hence, we propose that treatment with a recombinant globular domain of adiponectin (rgAd110-244) has significant therapeutic potential to treat insulin resistance. Mice were fed for 3 months on a high-fat diet (HFD) to induce insulin resistance, diabetes, and moderate weight gain. The mice were first infused iv with different doses of rgAd110-244 (0.12, 0.4, and 1.2 μg/kg · min) for 5 h. Basal and insulin-sensitive glucose use rates were assessed by the use of a submaximal rate of insulin in the awake free-moving mouse. rgAd110-244 reduced, with dose dependence, epinephrine-induced hyperglycemia and HFD-induced insulin resistance by increasing whole-body glucose use (35% at the highest dose) and glycolysis rates. Similarly, the reduction of plasma free fatty acid concentrations by insulin was dramatically improved. Basal hepatic glucose production was unchanged by rgAd110-244 infusion. This acute rgAd110-244 treatment improved glucose homeostasis and was associated with an increased content of muscle phospho-Akt, glycogen synthase kinase-3β, and AMP-activated kinase. Second, HFD mice were chronically treated with sc rgAd110-244 injections (10, 30, and 100 μg/kg). Fasting glycemia and insulin-sensitive glucose use were improved by rgAd110-244 at the highest dose at completion of the treatment, with concomitant reduction in body weight gain. We here show for the first time that a recombinant adiponectin fragment (110-244 amino acids called rgAd110-244) is able to treat insulin-resistant diabetes. Our results strongly suggest further pharmacological investigation of rgAd110-244 with the objective of developing a new treatment of insulin-resistant diabetes.
Absence of Estrogen Receptor-Related-α Increases Osteoblastic Differentiation and Cancellous Bone Mineral Density
Authors: Delhon I. , Gutzwiller S. , Morvan F. , Rangwala S. , Wyder L. , Evans G. , Studer A. , Kneissel M. , Fournier B.
Published: July 2009

The nuclear orphan receptor human estrogen receptor-related receptor (ERR)-α is implicated in bone metabolism. We studied the effect of ERRα silencing in human mesenchymal stem cells (hMSCs) during osteoblastogenesis. We found that ERRα silencing led to an increase of bone sialoprotein and a decrease of osteopontin mRNA levels, suggesting enhanced osteoblastic differentiation. This was confirmed by an increased ability of hMSCs to deposit calcium. Concomitantly, knockdown of ERRα inhibited adipogenesis, resulting in a decrease in adipocyte number and adipocyte marker gene expression. In line with a negative role of ERRα in bone metabolism, we found that adult female and male ERRα-deficient mice displayed a moderate increase in femoral cancellous bone volume and density. Osteoblast surface was increased and marrow fat volume decreased in these animals. Furthermore, ERRα-deficient osteoblasts displayed increased differentiation properties in vitro in line with our observations in hMSCs. In summary, we identified a role for ERRα in bone mass regulation by affecting osteoblastic differentiation.
C-Type Natriuretic Peptide Forms in Pregnancy: Maternal Plasma Profiles during Ovine Gestation Correlate with Placental and Fetal Maturation
Authors: McNeill Bryony A. , Barrell Graham K. , Wellby Martin , Prickett Timothy C. R. , Yandle Timothy G. , Espiner Eric A.
Published: July 2009

Circulating concentrations of C-type natriuretic peptide (CNP) and a related amino terminal fragment (NTproCNP) were measured at weekly intervals from preconception to 3 wk postpartum in ewes with twins (n = 8) and nonpregnant ewes (n = 8). In contrast to low and stable values in nonpregnant ewes (CNP, 0.75 ± 0.08; NTproCNP, 22 ± 2 pmol/liter), CNP forms increased abruptly at 40–50 d of gestation and rose to peak values (CNP, 31 ± 5, NTproCNP, 270 ± 16 pmol/liter) at about d 120. Approximately 7 d prepartum, the concentration of both CNP forms fell precipitously to preconception values immediately postpartum. In separate studies, circulating maternal CNP forms were positively related to fetal number at d 120. Consistent with a major contribution from the placenta to circulating levels, the concentrations of CNP forms were elevated in the placentome (cotyledon: CNP, 18 ± 4, NTproCNP, 52 ± 10 pmol/g; caruncle: CNP, 13 ± 3, NTproCNP, 31 ± 6 pmol/g) and much higher than those of intercaruncular uterine tissue (CNP, 0.19 ± 0.05, NTproCNP, 0.98 ± 0.2 pmol/g) in late-gestation ewes (P < 0.001, n = 4). These distinctive patterns of maternal plasma CNP forms, positive relation with fetal number, and greatly elevated protein concentrations in the placentome demonstrate the hormone’s strong relation to placental and fetal maturation. The findings provide a firm basis for future studies of the functional role of CNP in fetal-maternal welfare.
14-3-3 Protein Regulates Cell Adhesion in the Seminiferous Epithelium of Rat Testes
Authors: Wong Elissa W. P. , Sun Shengyi , Li Michelle W. M. , Lee Will M. , Cheng C. Yan
Published: July 2009

Polarity proteins have been implicated in regulating and maintaining tight junction (TJ) and cell polarity in epithelia. Here we report 14-3-3θ, the homolog of Caenorhabditis elegans Par5 in mammalian cells, which is known to confer cell polarity at TJ, is found at the apical ectoplasmic specialization (ES), a testis-specific adherens junction type restricted to the Sertoli cell-elongating spermatid interface, in which TJ is absent. 14-3-3θ was shown to play a critical role in conferring cell adhesion at the apical ES. A loss of 14-3-3θ expression at the apical ES was detected in the seminiferous epithelium before spermiation. Involvement of 14-3-3θ in Sertoli cell adhesion was confirmed by its knockdown by RNA interference in Sertoli cells cultured in vitro with established TJ permeability barrier that mimicked the blood-testis barrier (BTB) in vivo. Mislocalization of N-cadherin and zonula occludens-1, but not α- and β-catenins, was observed after 14-3-3θ knockdown in Sertoli cells, moving from the cell-cell interface to cytosol, indicating a disruption of cell adhesion. Studies by endocytosis assay illustrated that this loss of cell adhesion was mediated by an increase in the kinetics of endocytosis of N-cadherin and junctional adhesion molecule-A at the BTB, which may represent a general mechanism by which polarity proteins regulate cell adhesion. In summary, the testis is using 14-3-3θ to regulate cell adhesion at the apical ES to facilitate spermiation and at the BTB to facilitate the transit of preleptotene spermatocytes at stages VIII–IX of the epithelial cycle. 14-3-3θ may act as a molecular switch that coordinates these two cellular events in the seminiferous epithelium during spermatogenesis.
Theoretical analysis and realization of stepless capacity regulation for reciprocating compressors
Authors: Hong W , Jin J , Wu R , Zhang B
Published: July 2009

The present article focuses on a stepless capacity regulation system for reciprocating compressors in the capacity range between 0 and 100 per cent. This system is based on the so-called reverse flow regulation principle. The principle works by reversing part of the total gas that has been taken into the cylinder by conveying it back to the suction chamber by holding the suction valve open for a controlled and variable proportion of the compression stroke. Therefore the discharge capacity and power reduction are virtually proportional. In this study, the thermal cycle of reciprocating compressors in the case of stepless capacity regulation is analysed. The theoretical model of the thermodynamics cycle is first established. The relationship between the variation of the capacity and the opening time of the suction valve in a compression stroke can be obtained. Based on this approach, a new stepless capacity regulation system is designed, which consists of a hydraulic unit, a distributor, an unloader, and a control system. The resulting system is applied to a type 3L-10/8 reciprocating compressor to demonstrate its effectiveness. The experimental results show that the capacity of the compressor can be regulated steplessly, and the energy consumption is reduced proportionally with respect to the reduction in the capacity.
Enhancement of the finite-element method for the analysis of vertical train—track interactions
Authors: Yang S C
Published: July 2009

The accuracy of the simulation of train—track interaction can be improved by adding a node at the point of loading, when a contact force exists within the beam element that models the rail. This causes difficulties in the formulation and entails large computational times since the node moves along with the point of contact. In this study, a more simplified method that can represent the discontinuities of slope deflection at the location of both the sleeper and of the moving contact force, while employing the customary finite-element method, has been presented. The simulation of the existence of such an added node without explicitly including it is realized by modifying the Hertzian spring coefficient and adding the additional mass matrix to the existing mass matrix. Also, to enhance the convergence and to overcome the computational burden of load vector calculations at all iterations, a modified Newmark-β integral scheme is proposed. The suggested model was validated by comparing the results with field-test data and other numerical models reported in the literature by other researchers.
Pro-inflammatory, Pleiotropic, and Anti-inflammatory TNF-α, IL-6, and IL-10 in Experimental Porcine Intervertebral Disk Degeneration
Authors: Holm S. , Mackiewicz Z. , Holm A. K. , Konttinen Y. T. , Kouri V.-P. , Indahl A. , Salo J.
Published: July 2009

The aim of this study was to check the balance between tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in well-developed end-stage disk disease in the disk itself as well as in paradiskal spine. In 6 domestic pigs the cranial bony end plate of the L4 vertebra was perforated to the nucleus pulposus. At 3 months the degenerated experimental and contiguous control disks, together with the adjoining bony and cartilaginous vertebral end plates, bone marrow, and spinal ligaments, were excised and used for immunohistochemical analysis. In general, there were more TNF-α and in particular IL-10 positive cells in the degenerated disks than in the control disks, whereas the number of IL-6 labeled cells did not differ among sites or between control and experimental intervertebral disks. These results suggest that TNF-α and IL-10 are involved in the late reparatory phases of the experimental disk lesion. Use of an experimental model showed that strictly disk-directed manipulation and degeneration are also reflected in the contiguous vertebrae, including adjoining cartilage, bone, marrow, and ligaments.
Rectal Plasmacytoma with Intracellular Hemosiderin in a Dog
Authors: Rannou B. , Hélie P. , Bédard C.
Published: July 2009

An 11-year-old female American Cocker Spaniel was presented with a rectal mass that protruded through the anus. Cytologically, the mass was composed of neoplastic round cells consistent with an extramedullary plasmacytoma. Histiocytic sarcoma, carcinoid tumor, and melanoma were also considered because of the presence of golden-brown cytoplasmic granules. Histopathologic findings and immunohistochemical reactivity for lambda light chains confirmed the cytologic diagnosis of plasmacytoma. Prussian blue staining identified the cytoplasmic granules as hemosiderin. The granules were negative by Fontana Masson and Grimelius histochemistry. To our knowledge, this is the first report of an extramedullary plasmacytoma containing hemosiderin in a dog.
Feline Peripheral Nerve Sheath Tumors
Authors: Schulman F. Y. , Johnson T. O. , Facemire P. R. , Fanburg-Smith J. C.
Published: July 2009

Feline peripheral nerve sheath tumors are uncommonly reported, and their clinical behavior has not been well documented. Fifty-nine peripheral nerve sheath tumors were collected from 53 cats. All of the tumors involved skin, subcutis, skeletal muscle, and/or mucous membranes. Histologically, the tumors were composed of compact to loosely arranged streams and fascicles of spindled cells with eosinophilic, often wavy cytoplasmic processes; small to occasionally moderate amounts of collagenous to myxoid matrix; and nuclear palisading. Immunohistochemically, all tumors were positive for vimentin and S-100 protein, 44 of 59 were positive for glial fibrillary acidic protein (GFAP), and all were negative for muscle specific actin. The tumors fell into 3 histologic categories: 34 benign tumors with Antoni A areas that were S-100 protein and GFAP positive, 9 benign tumors that lacked Antoni A areas and were S-100 protein positive and GFAP negative, and 16 tumors with features of malignancy. Seventy-five percent of these cases involved the head, neck, or limbs. Recurrent tumors were submitted or tumors were reported to have recurred in 9 cases. Tumor recurrence was reported for all 3 of the histologic subtypes. None was documented as having metastasized.
Heterophilic antibodies may be a cause of falsely low total IGF1 levels
Authors: Brugts M P , Luermans J G L M , Lentjes E G W M , van Trooyen-van Vrouwerff N J , van der Horst F A L , Slee P H Th J , Lamberts S W J , Janssen J A M L
Published: July 2009

Background

A low serum total IGF1 is considered as a diagnostic indicator of GH deficiency (GHD) in the presence of hypopituitarism. Introduction of IRMA and chemiluminescent immunometric assay (CLIA) IGF1 immunoassays has introduced endogenous antibodies as a new source of interference. In general, this goes unnoticed and might lead to unnecessary diagnostic and therapeutic interventions.

Case

A 56-year-old man was referred with a decline in physical performance, unexplained osteopenia, and weight loss of 3 kg over the past 8 months. Although clinical signs and symptoms were unremarkable, laboratory results pointed to secondary hypothyroidism and secondary hypogonadism. In addition, the serum total IGF1 level (CLIA; Siemens Medical Solutions Diagnostics) was in the low normal range. Two GH stimulation tests were performed, but these tests did not support the diagnosis GHD. Moreover, IGF1 bioactivity measured by the kinase receptor activation assay was normal. Interference of heterophilic antibodies was considered. After pretreatment with specific heterophilic blocking tubes that contain blocking reagents to eliminate heterophilic antibodies, serum-free thyroxine, testosterone, and IGF1 levels turned out to be normal.

Conclusion

To the best of our knowledge, we here describe the first case in the literature of a patient with low serum total IGF1 levels due to interference from heterophilic antibodies in the used IGF1 immunoassay. When confronted with low-IGF1 levels that do not fit the clinical picture, interference of heterophilic antibodies should be considered in the differential diagnosis.
Random multitrees
Authors: Móri Tamás
Published: July 2009

A recursive random multitree process with a preferential attachment dynamics is studied. The asymptotic degree distribution is computed in the whole graph as well as nearby the initial configuration. The two distributions are not alike.
Rock around the clock
Authors: Monaghan Terry
Published: July 2009

The unruly surge of enthusiastic mass dancing to rock ’n’ roll music became a defining event of 1956, a year packed with memorable political and cultural changes. Through detailed analysis of key films from Rock Around the Clock to Jailhouse Rock, this article locates 1950s rock ’n’ roll on the cusp between the remnants of the swing era, and the subsequent period of music industry control. After the shock administered by mid-1956 rock ‘n’ roll music and mass dancing to the then prevailing racially segregated social norms, Hollywood films downplayed the role of dance and refocused creative audience interest on the ‘rock ‘n’ roll’ vocal stars.
Resource notes
Authors: Mäkelä Janne
Published: July 2009

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Use of growth retardants in wheat
Authors: Espindula M.C. , Rocha V.S. , Grossi J.A.S. , Souza M.A. , Souza L.T. , Favarato L.F.
Published: July 2009

In general, lodging has been controlled by restricting nitrogen fertilizer application and/or using short cultivars. Growth retardants can also be used to solve this problem.The objective of this study was to evaluate the effect of rates and application times of three growth retardants on Pioneiro wheat cultivar. The trial was carried out in Viçosa-MG, from May to September 2005, in a factorial and hierarchical scheme, in a randomized block design with four replications and a control treatment. The treatments consisted of 500, 1,000 and 1,500 g ha-1 of chlormequat; 62.5, 125 and 187.5 g ha-1 of trinexapac-ethyl and 40, 80 and 120 g ha-1 of paclobutrazol applied at growth stages 6 or 8, growth stage used on the scale of Feeks and Large, and a control treatment without growth retardant application. Only trinexapac-ethyl and chlormequat were efficient in reducing plant height; the effect of chlormequat and paclobutrazol on plant height was independent of the application time, but the trinexapac-ethyl at growth stage 8 produced shorter plant height than at stage 6. Increasing growth retardant rates produced shorter plant heights; chlormequat and paclobutrazol did not affect grain yield. However, the highest trinexapac-ethyl rates reduced wheat yield.
The Role of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer
Authors: Helm C. William
Published: July 2009

Overall outcomes for women with epithelial ovarian cancer (EOC) remain relatively poor, and superior methods of treatment are needed. EOC is a peritoneal surface malignancy that is relatively sensitive to chemotherapy agents, making it a good target for i.p. chemotherapy. Because there is strong laboratory data demonstrating the ability of hyperthermia to increase the efficacy of chemotherapeutic agents, the addition of hyperthermia to i.p. chemotherapy, hyperthermic intraperitoneal chemotherapy (HIPEC), makes theoretical sense. This article reviews the current literature and discusses the possible role for HIPEC in EOC at significant natural history time points: front line, at the time of interval debulking, in consolidation, and for recurrent disease. The conclusion is that much further research is needed but that HIPEC could sensibly be researched at all the natural history time points in EOC.