bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetraspanin CD151 Regulates Growth of Mammary Epithelial Cells in Three-Dimensional Extracellular Matrix: Implication for Mammary Ductal CarcinomaIn situ
Authors: Novitskaya Vera , Romanska Hanna , Dawoud Marwa , Jones J. Louise , Berditchevski Fedor
Published: May 2010

Tetraspanin CD151 is associated with laminin-binding integrins (i.e., α3β1, α6β1, and α6β4) and regulates tumor cell migration and invasion. Here, we examined the role of CD151 in proliferation of mammary epithelial cells using in vitro and in vivo models. Depletion of CD151 suppressed growth of HB2 cells, a nontumorigenic breast epithelial cell line, in three-dimensional (3D) extracellular matrices (ECM) and in Matrigel-based xenografts. Whereas the presence of α3β1 (but not α6 integrins) was necessary to support growth of HB2 cells in 3D ECM, the pro-proliferative activity of CD151 did not require direct interaction with integrins. Furthermore, depletion of CD151 potentiated formation of the internal lumen and partial restoration of polarity when HB2 cells were cultured in 3D ECM. This correlated with a decrease in phosphorylation levels of extracellular signal-regulated kinase 1/2 and cAkt in CD151-negative cells and increase in activation of caspase-3. Accordingly, the number of CD151-positive colonies with internal lumen was increased by ∼5-fold when cells were cultured in the presence of MAP/ERK kinase (U0126) and phosphoinositide 3-kinase (LY29004) inhibitors. To establish the physiologic relevance of pro-proliferative and morphogenetic activities of CD151, we analyzed the expression of this tetraspanin in ductal carcinoma in situ (DCIS), which is characterized by neoplastic proliferation of mammary epithelial cells. Strong homogeneous membrane expression of CD151 was found to be associated with a high grade of DCIS (P = 0.004). Taken together, these results strongly suggest that CD151 complexes play a crucial role in the development of hyperproliferative diseases in the mammary gland. Cancer Res; 70(11); 4698–708. ©2010 AACR.
Similar Nucleotide Excision Repair Capacity in Melanocytes and Melanoma Cells
Authors: Gaddameedhi Shobhan , Kemp Michael G. , Reardon Joyce T. , Shields Janiel M. , Smith-Roe Stephanie L. , Kaufmann William K. , Sancar Aziz
Published: May 2010

Sunlight UV exposure produces DNA photoproducts in skin that are repaired solely by nucleotide excision repair in humans. A significant fraction of melanomas are thought to result from UV-induced DNA damage that escapes repair; however, little evidence is available about the functional capacity of normal human melanocytes, malignant melanoma cells, and metastatic melanoma cells to repair UV-induced photoproducts in DNA. In this study, we measured nucleotide excision repair in both normal melanocytes and a panel of melanoma cell lines. Our results show that in 11 of 12 melanoma cell lines tested, UV photoproduct repair occurred as efficiently as in primary melanocytes. Importantly, repair capacity was not affected by mutation in the N-RAS or B-RAF oncogenes, nor was a difference observed between a highly metastatic melanoma cell line (A375SM) or its parental line (A375P). Lastly, we found that although p53 status contributed to photoproduct removal efficiency, its role did not seem to be mediated by enhanced expression or activity of DNA binding protein DDB2. We concluded that melanoma cells retain capacity for nucleotide excision repair, the loss of which probably does not commonly contribute to melanoma progression. Cancer Res; 70(12); 4922–30. ©2010 AACR.
Selective Depletion of CD4+CD25+Foxp3+ Regulatory T Cells by Low-Dose Cyclophosphamide Is Explained by Reduced Intracellular ATP Levels
Authors: Zhao Jie , Cao Yuchun , Lei Zhang , Yang Zhuoshun , Zhang Biao , Huang Bo
Published: May 2010

CD4+CD25+Foxp3+ regulatory T (Treg) cells have been shown to play important roles in mediating cancer development. Although cyclophosphamide (CY) has shown promise as a drug to selectively target Treg cells with low-dose in vivo, the underlying molecular mechanism remains unclear. In this report, we provide evidence that ATP, the energy molecule and signal element, accounts for the selective depletion of Treg cells by low-dose CY. Relative to conventional T cells or other cell types, ATP levels were much lower in Treg cells. This was due to Treg cells that downregulate one microRNA, miR-142-3p, and upregulate ecto-nucleoside triphosphate diphosphohydrolase CD39. The transfection of miR-142-3p or the blockade of CD39 could increase intracellular ATP levels of Treg cells, consequently decreasing the sensitivity of Treg cells to low-dose CY. On the other hand, the transfection of miR-142-3p inhibitor or the addition of soluble CD39 to the cultured CD4+CD25− T cells resulted in the decrease of intracellular ATP levels and increase of sensitivity of conventional T cells to low-dose CY. Furthermore, we found that the low levels of ATP attenuated the synthesis of glutathione, leading to the decrease of CY detoxification, thus increasing the sensitivity of Treg cells to low-dose CY. Therefore, we here identify a molecular pathway through which low-dose CY selectively ablates Treg cells. Our findings also imply that low levels of ATP are probably related to Treg cell function. Cancer Res; 70(12); 4850–8. ©2010 AACR.
ARF Suppresses Tumor Angiogenesis through Translational Control of VEGFA mRNA
Authors: Kawagishi Hiroyuki , Nakamura Hideaki , Maruyama Mitsuo , Mizutani Shuki , Sugimoto Kazushi , Takagi Masatoshi , Sugimoto Masataka
Published: May 2010

Vascular endothelial growth factor A (VEGFA) is a specific mitogen for vascular endothelial cells that plays a critical role in cancer neoangiogenesis. Here, we report that the nucleolar tumor suppressor p19ARF suppresses VEGFA expression, acting at the level of mRNA translation without affecting the transcription of the VEGFA gene. Translational repression of VEGFA mRNA by p19ARF does not require p53, a major target of the ARF tumor suppressor pathway, but instead correlates with binding to nucleophosmin/B23. Maintaining VEGFA expression relies on nucleophosmin/B23, and downregulating this protein by RNAi or p19ARF leads to translational repression of VEGFA. p19ARF inhibits VEGFA-dependent tumor angiogenesis in nude mice. Additionally, p14ARF expression and microvessel density are inversely correlated in human colon carcinomas. Taken together, our results define a mechanism by which the ARF tumor suppressor targets the translational repression of specific oncogenes during neoplastic transformation. Cancer Res; 70(11); 4749–58. ©2010 AACR.
Phase 1 Study of AMG 386, a Selective Angiopoietin 1/2–Neutralizing Peptibody, in Combination with Chemotherapy in Adults with Advanced Solid Tumors
Authors: Mita Alain C. , Takimoto Chris H. , Mita Monica , Tolcher Anthony , Sankhala Kamalesh , Sarantopoulos John , Valdivieso Manuel , Wood Leslie , Rasmussen Erik , Sun Yu-Nien , Zhong Z. Don , Bass Michael B. , Le NgocDiep , LoRusso Patricia
Published: May 2010

Purpose: To evaluate the safety, pharmacokinetics, and antitumor activity of AMG 386, an investigational selective angiopoietin 1/2-neutralizing peptibody, in combination with FOLFOX-4 (F), carboplatin/paclitaxel (C/P), or docetaxel (D), in adult patients with advanced solid tumors.

Experimental Design: Three cohorts of patients (F, n = 6; C/P, n = 8; D, n = 12) received one full cycle of chemotherapy alone during the pretreatment phase, followed by administration of AMG 386 10 mg/kg i.v. weekly in combination with chemotherapy until disease progression or intolerance. Safety and tolerability, tumor response, pharmacokinetic profiles, and biomarkers were assessed.

Results: Twenty-six patients were enrolled; 22 received treatment with AMG 386. No dose-limiting toxicities or grade 3 or 4 adverse events related to AMG 386 were reported. The most common adverse events were diarrhea and hypomagnesemia (n = 3 each). One patient developed grade 2 hypertension and one had grade 1 subconjunctival eye hemorrhage. No neutralizing antibodies to AMG 386 were detected. There were no pharmacokinetic interactions between AMG 386 and F, C/P, or D. One patient receiving AMG 386 plus C/P for bladder cancer refractory to gemcitabine/cisplatin had a complete response at week 8. The remaining best tumor responses were partial response (n = 3, one from each cohort), stable disease ≥8 weeks (n = 13), and progressive disease (n = 1).

Conclusions: Weekly administration of AMG 386 in combination with three common chemotherapy regimens was well tolerated in patients with advanced solid tumors. No pharmacokinetic interactions between AMG 386 and any of the tested chemotherapy regimens were noted. Promising antitumor activity was observed with all three treatment combinations. Clin Cancer Res; 16(11); 3044–56. ©2010 AACR.
Distinct Roles of Cytochrome P450 Reductase in Mitomycin c Redox Cycling and Cytotoxicity
Authors: Wang Yun , Gray Joshua P. , Mishin Vladimir , Heck Diane E. , Laskin Debra L. , Laskin Jeffrey D.
Published: May 2010

Mitomycin c (MMC), a quinone-containing anticancer drug, is known to redox cycle and generate reactive oxygen species. A key enzyme mediating MMC redox cycling is cytochrome P450 reductase, a microsomal NADPH-dependent flavoenzyme. In the present studies, Chinese hamster ovary (CHO) cells overexpressing this enzyme (CHO-OR cells) and corresponding control cells (CHO-WT cells) were used to investigate the role of cytochrome P450 reductase in the actions of MMC. In lysates from both cell types, MMC was found to redox cycle and generate H2O2; this activity was greater in CHO-OR cells (Vmax = 1.2 ± 0.1 nmol H2O2/min/mg protein in CHO-WT cells versus 32.4 ± 3.9 nmol H2O2/min/mg protein in CHO-OR cells). MMC was also more effective in generating superoxide anion and hydroxyl radicals in CHO-OR cells, relative to CHO-WT cells. Despite these differences in MMC redox cycling, MMC-induced cytotoxicity, as measured by growth inhibition, was similar in the two cell types (IC50 = 72 ± 20 nmol/L for CHO-WT and 75 ± 23 nmol/L for CHO-OR cells), as was its ability to induce G2-M and S phase arrest. Additionally, in nine different tumor cell lines, although a strong correlation was observed between MMC-induced H2O2 generation and cytochrome P450 reductase activity, there was no relationship between redox cycling and cytotoxicity. Hypoxia, which stabilizes MMC radicals generated by redox cycling, also had no effect on the sensitivity of tumor cells to MMC-induced cytotoxicity. These data indicate that NADPH cytochrome P450 reductase–mediated MMC redox cycling is not involved in the cytotoxicity of this chemotherapeutic agent. Mol Cancer Ther; 9(6); 1852–63. ©2010 AACR.
Oncogenic Functions of Secreted Frizzled-Related Protein 2 in Human Renal Cancer
Authors: Yamamura Soichiro , Kawakami Kazumori , Hirata Hiroshi , Ueno Koji , Saini Sharanjot , Majid Shahana , Dahiya Rajvir
Published: May 2010

The secreted Frizzled-related proteins (sFRP) are modulators of the Wnt signaling pathway, which is involved in embryonic development and tumor progression. The functions of sFRP2 have not been studied in renal cancer. Transient transfection of sFRP2 promoted cell growth in renal carcinoma cells, whereby the largest effect was observed in A498 cells. To further study the functions of sFRP2 gene in renal carcinoma cells, we established A498 renal cancer cell lines, which stably expressed sFRP2. Stably expressed sFRP2 significantly promoted cell proliferation in vitro and in vivo tumor growth. The stably expressed sFRP2 cells were also found to have reduced UV-induced apoptosis and increased G2 phase of the cell cycle. The phosphorylation level at Ser33/37/Thr41 of β-catenin was lower in the stable sFRP2 cell lines compared with the control cell line. sFRP2 significantly activated T-cell factor/lymphoid enhancer factor transcriptional activity. In the stable sFRP2 cell line, expression of c-Fos, Bcl2, Bcl-w, cyclin B2, and cyclin E2 genes was significantly increased and p53 expression was decreased. This is the first report documenting that sFRP2 activates the canonical Wnt pathway and promotes cell growth by evoking diverse signaling cascades in renal cancer cells. This study may provide better strategies for the management of renal cancer through regulation of sFRP2 pathways. Mol Cancer Ther; 9(6); 1680–7. ©2010 AACR.
Crosstalk of EDA-A2/XEDAR in the p53 Signaling Pathway
Authors: Tanikawa Chizu , Ri Cui , Kumar Vinod , Nakamura Yusuke , Matsuda Koichi
Published: May 2010

We recently identified X-linked ectodermal dysplasia receptor (XEDAR, also known as TNFRSF27 or EDA2R) as a direct p53 target that was frequently downregulated in colorectal cancer tissues due to its epigenetic alterations or through the p53 gene mutations. However, the role of the posttranslational regulation of XEDAR protein in colorectal carcinogenesis was not well clarified thus far. Here, we report that the extracellular NH2 terminus of XEDAR protein was cleaved by a metalloproteinase and released into culture media. The remaining COOH-terminal membrane–anchored fragment was rapidly degraded through the ubiquitin-proteasome pathway. Interestingly, ectopic p53 expression also transactivated an XEDAR ligand, EDA-A2, together with XEDAR. Moreover, EDA-A2 blocked the cleavage of XEDAR and subsequently inhibited cell growth. We also found a missense mutation of the XEDAR gene in NCI-H716 colorectal cancer cells, which caused the translocation of XEDAR protein from cell membrane to cytoplasm. This mutation attenuated the growth-suppressive effect of XEDAR, indicating that membrane localization is critical for physiologic XEDAR function. Thus, our findings clearly revealed the crucial role of EDA-A2/XEDAR interaction in the p53-signaling pathway. Mol Cancer Res; 8(6); 855–63. ©2010 AACR.
A New Story about an Old Guy: Is Alzheimer’s Disease Infectious?
Authors: Reis Helton J. , Mukhamedyarov Marat A. , Rizvanov Albert A. , Palotás András
Published: May 2010

Protein aggregation and amyloid fibril deposits in the central nervous system are characteristic features of more than 2 dozens of pathologic conditions. The various peptides thought to underlie these disorders have striking structural and functional similarities. The main difference between them at the molecular level is whether they are endogenously produced particles, exogenously transmitted infectious agents, or both. These similarities and novel approaches to their transmissibility are discussed in this review-based hypothesis.
A Reliability and Validity Study of the Cornell Scale among Elderly Inpatients, Using Various Clinical Criteria
Authors: Barca Maria Lage , Engedal Knut , Selbæk Geir
Published: May 2010

Background: The validity of the Cornell Scale for Depression in Dementia is seldom studied in institutions. Method: Two reliability studies, with 103 and 32 patients, and a validity study with 231 patients in nursing homes and in hospital were performed. They were assessed by the Cornell Scale, Clinical Dementia Rating scale and Self-Maintenance scale. A psychiatrist ‘blind’ to the Cornell assessment diagnosed depression according to the ICD-10, DSM-IV-TR and the Provisional Criteria for Depression in Alzheimer’s Disease (PCD-dAD). Results: Cronbach’s α values were 0.81 and 0.95, and the mean ĸ for the Cornell items were 0.91 and 0.57, respectively. In the validity study, 164 subjects had dementia; 105 (45.5%) had depression according to the ICD-10, 68 (29.9%) according to the DSM-IV-TR and 88 (53.3%) of the demented patients had depression according to the PCD-dAD. In the receiver operating characteristic analysis, the DSM-IV-TR criteria produced the highest area under the curve, i.e. 0.81 (95% CI: 0.75–0.87). A range of cutoff points for a depressive disorder was found for the various clinical criteria. Conclusion: The Cornell Scale is reliable and a range of cutoff points should be used for various clinical criteria of depression.
Preoperative Prediction of Outcome in 283 Poor-Grade Patients with Subarachnoid Hemorrhage: A Project of the Chugoku-Shikoku Division of the Japan Neurosurgical Society
Authors: Shirao Satoshi , Yoneda Hiroshi , Kunitsugu Ichiro , Ishihara Hideyuki , Koizumi Hiroyasu , Suehiro Eiichi , Nomura Sadahiro , Kato Shoichi , Fujisawa Hirosuke , Suzuki Michiyasu
Published: May 2010

Background: The management of patients with poor-grade subarachnoid hemorrhage (SAH) continues to be controversial. The objective of this study was to examine predictors of outcome of poor-grade SAH after surgical obliteration of the aneurysm. Methods: The study was performed as a retrospective review of 283 patients with poor-grade SAH who underwent surgical obliteration of the aneurysm at multiple centers in Chugoku and Shikoku, Japan. Results: A favorable outcome at discharge was achieved in 97 of the 283 patients (34.3%). Age (p < 0.001), World Federation of Neurosurgical Societies (WFNS) grade V at admission (p = 0.002), improvement in WFNS grade after admission (p = 0.002), Fisher grade (p = 0.039) and a low-density area (LDA) associated with vasospasm on computed tomography (CT; p < 0.001) showed a significant association with outcome. Further analysis of WFNS grades indicated that most patients who only improved to preoperative grade IV from grade V at admission did not have a favorable outcome. Multivariate analysis identified age (especially of ≧65 years; p < 0.001), WFNS grade V (p < 0.001) and LDA associated with vasospasm on CT (p < 0.001) as predictors of a poor outcome, and improvement in WFNS grade (p = 0.001) as a predictor of a favorable outcome after surgical obliteration of the aneurysm. Conclusions: Advanced age, WFNS grade V, improvement in WFNS grade, and LDA associated with vasospasm on CT were found to be independent predictors of clinical outcome, whereas rebleeding, early aneurysm surgery and treatment modality (surgical clipping or Guglielmi detachable coil embolization) were not independently associated with outcome in patients with poor-grade aneurysm.
Possible Detrimental Effects of Cognitive Behaviour Therapy for Chronic Fatigue Syndrome
Authors: Heins Marianne J. , Knoop Hans , Prins Judith B. , Stulemeijer Maja , van der Meer Jos W.M. , Bleijenberg Gijs
Published: May 2010

Background: Cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) can decrease the level of fatigue and disabilities, but it has been suggested that during therapy some patients experience a deterioration of their symptoms rather than an improvement. The aim of this study is to examine the frequency and severity of symptom deterioration during CBT for CFS. Methods: Data from 3 randomised controlled trials on CBT for CFS were pooled and reanalysed. Symptom deterioration during the trial was rated by patients and measured as deterioration in fatigue, pain, functional impairment and psychological distress. Both the frequency and severity of deterioration in these domains were compared between the patients receiving CBT and those in the control group. Predictors of symptom deterioration were identified by comparing their means in patients with and without an increase in fatigue. Statistically significant predictors were then combined in a logistic regression model. Results: The frequency of symptom deterioration varied from 2 to 12% in patients receiving CBT and from 7 to 17% in the control group. None of the measures showed a significantly higher frequency of symptom deterioration in the CBT group. The severity of deterioration was also comparable in the CBT and in the control group. No predictors of symptom deterioration specific to CBT were found. Conclusion: Patients receiving CBT do not experience more frequent or more severe symptom deterioration than untreated patients. The reported deterioration during CBT seems to reflect the natural variation in symptoms. Thus, CBT is not only a helpful, but also a safe treatment for CFS.
Improvements in Symptoms and Quality of Life following Exercise Training in Older Adults with Moderate/Severe Persistent Asthma
Authors: Turner Sian , Eastwood Peter , Cook Angus , Jenkins Sue
Published: May 2010

Background: Some individuals with moderate/severe persistent asthma develop irreversible airway obstruction. These individuals present with dyspnoea, exercise intolerance and impaired quality of life (QOL), all of which could potentially be alleviated with exercise training. Objective: To investigate whether exercise training improves functional exercise capacity and QOL in middle-aged and older adults with fixed airway obstruction asthma (FAOA). Methods: 35 subjects aged 67.8 ± 10.6 years, with FEV1 59 ± 16% of predicted, were randomised to a 6-week ‘intervention’ period of supervised exercise training (n = 20) or usual care (n = 15). This period was preceded by a 3-week run-in period during which asthma control was assessed weekly. Functional exercise capacity (6-min walk distance, 6MWD) and QOL (Asthma QOL Questionnaire, AQLQ) were measured before, immediately following and 3 months after the intervention period. Results: 34 subjects (exercise group, n = 19, and control group, n = 15) completed the intervention period. Relative to the control group, the exercise group had greater improvements immediately following and 3 months after the intervention in the AQLQ symptom domain (0.61, p = 0.001, and 0.57 points per item, p = 0.005) and AQLQ activity limitation domain (0.43, p = 0.04, and 0.55 points per item, p = 0.04). 6MWD increased (36 ± 37 m, p < 0.01) in the exercise group immediately following training and remained elevated (34 ± 45 m, p < 0.01) at the 3-month follow-up. The magnitude of change in 6MWD between groups was not significant, despite no change in the control group. Conclusions: Supervised exercise training improves symptoms and QOL in adults with FAOA.
A Qualitative and Quantitative Evaluation of Parkinsonians Three to Six Years Following Thalamotomy (Part 2 of 2)
Authors: Van Buren J.M. , Li Choh-Luh , Shapiro D.Y. , Henderson W.G. , Sadowsky Doris A.
Published: May 2010

Seventy-eight patients with parkinsonism have been assessed over a postoperative interval of 3–6 years from 3 major aspects: (1) history and physical examination, (2) specific psychological tests, and (3) a battery of clinical quantitative neurological tests. The results were separated into the effects of (1) the first thalamotomy, (2) the second thalamotomy, and (3) thalamotomy plus L-dopa therapy. 1. The first thalamotomy. Contralateral tremor and rigidity both responded well to surgery in the qualitative and quantitative evaluations and remained at an improved level for about three years. Although general function was also usually improved over this interval, removal of tremor and rigidity did not guarantee functional improvement. Progression in bradykinesia, speech and mental symptoms did not change with thalamotomy. 2. The second thalamotomy. The results were similar but not as good quantitatively nor as enduring as those of the first thalamotomy. An adverse effect on mental symptoms was seen more frequently. 3. Thalamotomy plus L-dopa. The drug appeared to have specific action on bradykinesia, appeared synergistic with surgery in relieving rigidity and to a lesser degree, tremor. L-Dopa-resistent tremor responded to thalamotomy as well as the general tremor category in the pre-L-dopa period. Thalamotomy usually prevents iatrogenic L-dopa-induced dyskinesias in the limbs contralateral to the side of surgery, but had no certain effect upon the commoner facial and axial dyskinesias.
The Basal Ganglia-Circa 1982 (Part 2 of 2)
Authors: Mehler William R.
Published: May 2010

Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's [88] proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's [72] more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement.
“Our Gratitude to Our Soldiers”: Military Spouses, Family Re-Unification, and Postwar Immigration Reform
Authors: Wolgin Philip E. , Bloemraad Irene
Published: May 2010

The perceived need to re-unite military families after World War II, initially addressed by ad-hoc war-brides legislation, played a key role in the reformulation of U.S. immigration policy. The large number of military spouses, especially from Asia, pushed policymakers to revise their notions of racial admissibility, thus helping to establish family re-unification as the driving force behind immigration reform. Though unnoticed at the time, the combination of wartime service, patriotism, and marriage formed an inadvertent road map for the family-centric, and ultimately racially neutral, admissions policies that would dominate U.S. immigration law after 1965. The importance of Asian war brides in shaping the contours of U.S. policy stands in even stronger relief when compared to the relative unimportance of the issue in Canada, another major participant in World War II, which also pursued immigration reform during the 1960s.
Reconceptualizing the Republic: Diversity and Education in France, 1945–2008
Authors: Soysal Yasemin Nuhoğlu , Szakács Simona
Published: May 2010

Since the nineteenth century, France, not unlike the United States, has experienced significant immigration and, as a result, great flux. Yet, the French public discourse and policy instruments concerned with ethnic and racial diversities evolved in sharp contrast to those in the United States. Whereas U.S. nation-building incorporated the recognition of ethnoracial identities, with all of its trials and tribulations, the French nation's trajectory assumed a unitary form. Recent developments, however, point to changes in the Republic's projection of its identity and its citizenry. An analysis of school teaching finds that the Republic is now re-envisioned as open and tolerant of diversity, though more from a universalistic, normative perspective—increasingly indexed at the transnational level—than from a perspective that privileges France's immigrant and colonial past.
Mapping International Relations Teaching and Research in Indian Universities
Authors: Sharma Devika
Published: May 2010

Although the Indian International Relations (IR) community has been actively engaged in self-reflection, this has not translated into greater contribution at the international level. Part of the answer lies in the way IR in India has grown—institutionally, pedagogically, academically and as a research activity. The article seeks to assess the strengths and weaknesses of IR teaching and research in India on the basis of three parameters, that is, the papers taught in the M.A. programmes, the themes of research at the doctoral level and publications by IR scholars in select journals. On the basis of the weaknesses identified, the article offers some recommendations, which the IR community in India can adopt.
Development of International Relations Theory in China
Authors: Yaqing Qin
Published: May 2010

The article seeks to trace the development of International Relations Theory (IRT) in China since 1978. Based on the data collected from five major International Relations (IR) journals published in China as well as a series of translated Western classics and important IRT works by Chinese scholars, the article concludes that two parallel processes are at work in China over the last thirty years. One is a tenacious learning process aimed at knowledge acquirement and generation. It is primarily a process of learning from the West, especially the US, through which IR has developed as an independent academic discipline in China. The resulting triangular competition for influence among the three imported schools of IRT, that is, Realism, Liberalism and Constructivism coincides with the internal debates on China’s rise and integration into the international community. The other is a process of developing a Chinese school of IRT. Dissatisfied with the dominance of Western theoretical discourse in the Chinese context, scholars in China have been trying to bring Chinese thoughts back in and establish a distinctly Chinese perspective on IRT.
Liberalism in a Realist World
Authors: Ikenberry G. John
Published: May 2010

The study of international relations (IR) is a worldwide pursuit with each country having its own theoretical orientations, preoccupations and debates. Beginning in the early twentieth century, the US created its own scholarly traditions of IR. Eventually, IR became an American social science with the US becoming the epicentre for a worldwide IR community engaged in a set of research programmes and theoretical debates. The discipline of IR emerged in the US at a time when it was the world’s most powerful state and a liberal great power caught in a struggle with illiberal rivals. This context ensured that the American theoretical debates would be built around both power and liberal ideals. Over the decades, the two grand projects of realism and liberalism struggled to define the agenda of IR in the US. These traditions have evolved as they attempted to make sense of contemporary developments, speak to strategic position of the US and its foreign policy, as well as deal with the changing fashions and standards of social science. The rationalist formulations of realism and liberalism sparked reactions and constructivism has arisen to offer counterpoints to the rational choice theory.
The Impact of Transit-oriented Development on Housing Prices in San Diego, CA
Authors: Duncan Michael
Published: May 2010

This research measures the influence of transit-oriented development (TOD) on the San Diego, CA, condominium market. Many view TOD as a key element in creating a less auto dependent and more sustainable transport system. Price premiums indicate a potential for a market-driven expansion of TOD inventory. A hedonic price model is estimated to isolate statistically the effect of TOD. This includes interaction terms between station distance and various measures of pedestrian orientation. The resulting model shows that station proximity has a significantly stronger impact when coupled with a pedestrian-oriented environment. Conversely, station area condominiums in more auto-oriented environments may sell at a discount. This indicates that TOD has a synergistic value greater than the sum of its parts. It also implies a healthy demand for more TOD housing in San Diego.
The trajectory of palliative care costs over the last 5 months of life: a Canadian longitudinal study
Authors: Dumont Serge , Jacobs Philip , Turcotte Véronique , Anderson Donna , Harel François
Published: May 2010

Objective: This study aimed to highlight the trajectory of palliative care costs over the last five months of life in five urban centres across Canada.

Subjects: The study sample was comprised of 160 terminally ill patients and their main informal caregivers.

Research Design: A first interview took place in the patient’s home, and subsequent follow-up interviews were conducted by telephone at two week intervals until the patient’s passing.

Measures: Participants were asked to provide information on the goods and services they used related to the patients’ health condition, and on informal caregiving time.

Results: The overall costs of care gradually increased from the fifth to the last month of the patients’ life. A large part of this cost increase was attributable to inpatient care. Among outpatient care costs the largest increase was observed for home care. Informal care costs were particularly high over the last 3 months of life.

Conclusions: The knowledge gained from this study would be useful to policy makers when developing policies that could help families caring for a terminally ill loved one at home.
Connecting the Individual and Cultural Level Value Analysis
Authors: Ehala Martin
Published: May 2010

The studies of cultural dimensions have often shown that the values that are conceptually oppositional behave independently in empirical studies. This article addresses this apparent controversy in an attempt to operationalize one such bipolar value dimension: the utilitarianism–traditionalism scale. The empirical study of this dimension in Estonian and Russian populations in Estonia showed that these value groups are not related on the individual level. It is suggested that the combination of these two values leads to a four-member typology that corresponds to Berry’s typology of acculturation attitudes: utilitarianist (assimilationist), traditionalist (segregationalist), modernist (integrationalist), and distancing (marginalizationalist). This allows the results of the empirical study to be transformed to a single dimension, corresponding to the semantic structure of this opposition. It is suggested that the mathematical formula for this could also be used in other pairs of values that are semantically oppositional, but allow all logical combinations on the individual level.
School Nurse Online Emergency Preparedness Training
Authors: Elgie Robert , Sapien Robert , Fullerton Lynne , Moore Brian
Published: May 2010

The objective of this study was to evaluate the effectiveness of a computer-assisted emergency preparedness course for school nurses. Participants from a convenience sample (52) of school nurses from New Mexico were randomly assigned to intervention or control groups in an experimental after-only posttest design. Intervention group participants completed 15 online emergency preparedness training modules followed by posttests, and control group participants completed the posttests without taking the training modules. Tests measured emergency preparedness with written exams, confidence surveys, and skills performance in videotaped scenarios; the videotaped scenarios were scored by Pediatric Emergency Medicine physicians blinded to whether the participants were in the intervention or control group. The intervention group participants scored significantly higher in tests of knowledge and skills than control group participants. Confidence Survey scores did not differ significantly. The online training modules are a valuable resource for improving school nurse emergency preparedness knowledge and skills but may not affect participants' confidence.
The Effect of Retroperitoneal Fat Mass on Surgical Outcomes in Patients Performing Laparoscopic Adrenalectomy: The Effect of Fat Tissue in Adrenalectomy
Authors: Erbil Yeşim , Barbaros Umut , Sarı Serkan , Agcaoglu Orhan , Salmaslıoglu Artur , Ozarmagan Selcuk
Published: May 2010

Background: Obesity and visceral fat are thought to be the most important factors influencing the technical difficulty during open and laparoscopic surgery. The authors aimed to investigate the effect of retroperitoneal fat mass on surgical outcomes in patients undergoing laparoscopic adrenalectomy. Patients and methods: This prospective study included 51 consecutive patients who underwent lateral transabdominal laparoscopic adrenalectomy. Body mass index (BMI) and retroperitoneal fat area (RFA)/adrenal mass area (AMA) ratio were calculated. Results: There was a positive correlation between BMI and operating time and postoperative complications and hospital stay. According to 2-way analysis of variance, only RFA/AMA ratio ( P = .0001) was found to significantly correlate with operating time, whereas BMI did not significantly correlate with operating time ( P = .51). In patients with high BMI, high RFA indicated longer operating time and higher complication rate, whereas low RFA was associated with significantly shorter operating time and decreased risk of complications. Conclusion: Retroperitoneal fat mass is a more useful parameter than BMI for predicting the surgical outcomes of laparoscopic adrenalectomy.
Contribution of the C-terminal end of apolipoprotein AI to neutralization of lipopolysaccharide endotoxic effect
Authors: Henning María F. , Herlax Vanesa , Bakás Laura
Published: May 2010

It is well known that high density lipoprotein (HDL) binds bacterial lipopolysaccharide (LPS) and neutralizes its toxicity. The aim of this work was to study changes in the apolipoprotein (apo) AI structure after its interaction with LPS as well as to determine the protein domain involved in that interaction. The presented data indicate that LPS does not lead to major changes in the structure of apoAI, judging from Trp fluorescence spectra. However, analysis of denaturation behavior and binding of ANS show that LPS induces a loosened protein conformation. Further evidence for an apoAI—LPS specific interaction was obtained by incubation of the protein with 125I-ASD-LPS. The results show that multiple regions of the protein were able to interact with LPS, according to its amphiphatic nature. Finally, the contribution of the purified C-terminal fragment of the protein in the endotoxin neutralization was evaluated in comparison with the effect of apoAI. In both cases, the same decrease in tumor necrosis factor-α released was observed. This result suggests that the C-terminal half of apoAI is the main domain responsible of the neutralization effect of this protein. Our data may provide innovative pharmacological tools in endotoxin neutralization therapies.
Rifaximin therapy for metronidazole-unresponsive Clostridium difficile infection: a prospective pilot trial
Authors: Basu P. Patrick , Dinani Amreen , Rayapudi Krishna , Pacana Tommy , Shah Niraj James , Hampole Hemant , Krishnaswamy N.V. , Mohan Vinod
Published: May 2010

Background: Clostridium difficile infection (CDI) is a recent epidemic in the United States, particularly in the hospital setting. Oral metronidazole is standard therapy for C. difficile infection, but resistance to metronidazole is becoming a clinical challenge.

Methods: We evaluated the efficacy of the nonsystemic oral antibiotic rifaximin for the treatment of metronidazole-resistant C. difficile infection. Twenty-five patients with C. difficile infection were enrolled in the study. All had mild-to-moderate C. difficile infection (5—10 bowel movements a day without sepsis) unresponsive to metronidazole (i.e. stools positive for toxins A and B after oral metronidazole 500 mg three times daily [t.i.d.] for 5 days). After discontinuation of metronidazole, rifaximin 400 mg t.i.d. for 14 days was prescribed. Patients were followed for 56 days and stool was tested for C. difficile using polymerase chain reaction (PCR) to assess the effect of treatment. A negative PCR test result was interpreted as a favorable response to rifaximin.

Results: Sixteen of 22 patients (73%) were eligible for study inclusion and completed rifaximin therapy experienced eradication of infection (stool negative for C. difficile) immediately after rifaximin therapy and 56 days post-treatment. Three patients (12%) discontinued therapy because of abdominal distention. Rifaximin was generally well tolerated.

Conclusions: In conclusion, rifaximin may be considered for treatment of mild-to-moderate C. difficile infection that is resistant to metronidazole. Larger randomized trials are needed to confirm these positive findings.
Isolated Unilateral Brachial Neuritis of the Phrenic Nerve (Parsonage-Turner Syndrome) in a Marathon Runner With Exertional Dyspnea
Authors: Weng Modern , Fidel Constance
Published: May 2010

Parsonage-Turner syndrome, or acute brachial neuritis/plexitis, is a rare condition that should be included in the differential diagnosis of any athlete who presents with antecedent flulike symptoms, with progression to significant neuropathic pain, followed by profound weakness in the affected upper extremity. In rare cases, the main presenting symptom of this condition may be dyspnea on exertion secondary to an isolated unilateral brachial neuritis of the phrenic nerve.
Importance of replication in analyzing time-series gene expression data: Corticosteroid dynamics and circadian patterns in rat liver
Authors: Nguyen Tung T , Almon Richard R , DuBois Debra C , Jusko William J , Androulakis Ioannis P
Published: May 2010

Background

Microarray technology is a powerful and widely accepted experimental technique in molecular biology that allows studying genome wide transcriptional responses. However, experimental data usually contain potential sources of uncertainty and thus many experiments are now designed with repeated measurements to better assess such inherent variability. Many computational methods have been proposed to account for the variability in replicates. As yet, there is no model to output expression profiles accounting for replicate information so that a variety of computational models that take the expression profiles as the input data can explore this information without any modification.

Results

We propose a methodology which integrates replicate variability into expression profiles, to generate so-called 'true' expression profiles. The study addresses two issues: (i) develop a statistical model that can estimate 'true' expression profiles which are more robust than the average profile, and (ii) extend our previous micro-clustering which was designed specifically for clustering time-series expression data. The model utilizes a previously proposed error model and the concept of 'relative difference'. The clustering effectiveness is demonstrated through synthetic data where several methods are compared. We subsequently analyze in vivo rat data to elucidate circadian transcriptional dynamics as well as liver-specific corticosteroid induced changes in gene expression.

Conclusions

We have proposed a model which integrates the error information from repeated measurements into the expression profiles. Through numerous synthetic and real time-series data, we demonstrated the ability of the approach to improve the clustering performance and assist in the identification and selection of informative expression motifs.
Some novel intron positions in conserved Drosophila genes are caused by intron sliding or tandem duplication
Authors: Lehmann Jörg , Eisenhardt Carina , Stadler Peter F , Krauss Veiko
Published: May 2010

Background

Positions of spliceosomal introns are often conserved between remotely related genes. Introns that reside in non-conserved positions are either novel or remnants of frequent losses of introns in some evolutionary lineages. A recent gain of such introns is difficult to prove. However, introns verified as novel are needed to evaluate contemporary processes of intron gain.

Results

We identified 25 unambiguous cases of novel intron positions in 31 Drosophila genes that exhibit near intron pairs (NIPs). Here, a NIP consists of an ancient and a novel intron position that are separated by less than 32 nt. Within a single gene, such closely-spaced introns are very unlikely to have coexisted. In most cases, therefore, the ancient intron position must have disappeared in favour of the novel one. A survey for NIPs among 12 Drosophila genomes identifies intron sliding (migration) as one of the more frequent causes of novel intron positions. Other novel introns seem to have been gained by regional tandem duplications of coding sequences containing a proto-splice site.

Conclusions

Recent intron gains sometimes appear to have arisen by duplication of exonic sequences and subsequent intronization of one of the copies. Intron migration and exon duplication together may account for a significant amount of novel intron positions in conserved coding sequences.
Functional and gene network analyses of transcriptional signatures characterizing pre-weaned bovine mammary parenchyma or fat pad uncovered novel inter-tissue signaling networks during development
Authors: Piantoni Paola , Bionaz Massimo , Graugnard Daniel E , Daniels Kristy M , Everts Robin E , Rodriguez-Zas Sandra L , Lewin Harris A , Hurley Hurley L , Akers Michael , Loor Juan J
Published: May 2010

Background

The neonatal bovine mammary fat pad (MFP) surrounding the mammary parenchyma (PAR) is thought to exert proliferative effects on the PAR through secretion of local modulators of growth induced by systemic hormones. We used bioinformatics to characterize transcriptomics differences between PAR and MFP from ~65 d old Holstein heifers. Data were mined to uncover potential crosstalk through the analyses of signaling molecules preferentially expressed in one tissue relative to the other.

Results

Over 9,000 differentially expressed genes (DEG; False discovery rate ≤ 0.05) were found of which 1,478 had a ≥1.5-fold difference between PAR and MFP. Within the DEG highly-expressed in PAR vs. MFP (n = 736) we noted significant enrichment of functions related to cell cycle, structural organization, signaling, and DNA/RNA metabolism. Only actin cytoskeletal signaling was significant among canonical pathways. DEG more highly-expressed in MFP vs. PAR (n = 742) belong to lipid metabolism, signaling, cell movement, and immune-related functions. Canonical pathways associated with metabolism and signaling, particularly immune- and metabolism-related were significantly-enriched. Network analysis uncovered a central role of MYC, TP53, and CTNNB1 in controlling expression of DEG highly-expressed in PAR vs. MFP. Similar analysis suggested a central role for PPARG, KLF2, EGR2, and EPAS1 in regulating expression of more highly-expressed DEG in MFP vs. PAR. Gene network analyses revealed putative inter-tissue crosstalk between cytokines and growth factors preferentially expressed in one tissue (e.g., ANGPTL1, SPP1, IL1B in PAR vs. MFP; ADIPOQ, IL13, FGF2, LEP in MFP vs. PAR) with DEG preferentially expressed in the other tissue, particularly transcription factors or pathways (e.g., MYC, TP53, and actin cytoskeletal signaling in PAR vs. MFP; PPARG and LXR/RXR Signaling in MFP vs. PAR).

Conclusions

Functional analyses underscored a reciprocal influence in determining the biological features of MFP and PAR during neonatal development. This was exemplified by the potential effect that the signaling molecules (cytokines, growth factors) released preferentially (i.e., more highly-expressed) by PAR or MFP could have on molecular functions or signaling pathways enriched in the MFP or PAR. These bidirectional interactions might be required to coordinate mammary tissue development under normal circumstances or in response to nutrition.