bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathways to Childlessness
Authors: Hagestad Gunhild O. , Call Vaughn R. A.
Published: September 2007

In this article life history data from the U.S. National Survey of Families and Households (NSFH), and the Dutch survey on Older Adults' Living Arrangements and Social Networks (NESTOR-LSN) are used to shed light on the various pathways leading to and associated with childlessness, and the proportions of men and women who have followed a particular pathway (e.g., marrying late, divorcing early, never leaving the parental home). The central question is whether the childless took different routes during early adulthood in the domains of family, education, and employment. Data point to the critical importance of transition timing, especially with regard to leaving the parental home and marrying. Delayed transitions had domino effects and blocked second chances at securing an economic base and becoming a parent.
Reproducibility and validity of the Dutch Life Habits Questionnaire (LIFE-H 3.0) in older adults
Authors: Lemmens Jessie , ISM van Engelen Eveline , Post Marcel WM , de Witte Luc P , Beurskens AJHM , Wolters Pieter MJC , de Witte Luc P
Published: September 2007

Objective: To examine the reproducibility, the discriminant and convergent validity and feasibility of the Dutch translation of the self-administered Life Habits Questionnaire (LIFE-H).

Design: Three cross-sectional community-based studies on clinimetric properties of a measurement instrument.

Subjects: Older adults (n = 85) with functional limitations due to various chronic illnesses and healthy older adults (n = 40).

Measurement protocol: Participants of the reproducibility study (n = 35) filled out the LIFE-H twice in a two-week time period. In the discriminant validity study (n = 120), LIFE-H scores of healthy and ill subjects were compared. In the convergent validity study (n = 63), correlations were examined between LIFE-H, the Impact on Participation and Autonomy questionnaire and the London Handicap Scale.

Results: The test—retest reliability showed a satisfactory intraclass correlation coefficient for the total overall score (0.80) but not for the categories scores. The discriminant validity study showed significant differences between the healthy and ill subjects for the 10 separate categories (P < 0.01) and the total score (P < 0.001). The correlations between the LIFE-H categories and total scores and the Impact on Participation and Autonomy Questionnaire (0.80—0.82) and London Handicap Scale (0.89—0.92) were strong. Feasibility testing showed that the subjects experienced difficulties due to the long and fairly complex instructions and structure of the LIFE-H.

Conclusions: The clinimetric properties of the LIFE-H were moderate to good. The validity of LIFE-H was as good as the validity of the Impact on Autonomy and Participation and the London Handicap Scale, but the latter questionnaires were shorter and much easier to administer.
Evaluation of a single-item screening tool for depression after stroke: a cohort study
Authors: Watkins Caroline L. , Lightbody C. Elizabeth , Sutton Chris J. , Holcroft Leanne , Jack Cathy I.A. , Dickinson Hazel A. , van den Broek Martin D. , Leathley Michael J.
Published: September 2007

Objectives: To determine the accuracy and utility of a single-item screening tool for depression (the Yale, taken from the Yale—Brown Obsessive Compulsive Scale) in patients who have recently had a stroke.

Design: Comparison of a clinical classification of depression with a screening tool in a defined cohort.

Setting: A large teaching hospital in Liverpool, UK.

Subjects: One hundred and twenty-two consecutive people admitted with an acute stroke who did not have severe cognitive or communication problems, and who were still in hospital in the second week post stroke.

Main measures: Classification of depression using the Montgomery-Asberg Depression Rating Scale was compared with the Yale, a single-item screening tool.

Results: When comparing the classification of depression according to the Montgomery-Asberg Depression Rating Scale and the response to the Yale we found that at week 2 the Yale had a sensitivity of 86% (57/66), a specificity of 84% (46/55), a positive predictive value of 86% (57/66) and a negative predictive value of 84% (46/55), with an overall efficiency of 85% (103/121); prevalence of depression was 54% (according to the Montgomery-Asberg Depression Rating Scale). At month 3 the Yale had a sensitivity of 95% (52/55), a specificity of 89% (32/36), a positive predictive value of 93% (52/56) and a negative predictive value of 91% (32/35), with an overall efficiency of 92% (84/91); prevalence of depression was 60%.

Conclusions: The Yale, which only requires a `yes' or `no' answer to a single question, may prove a useful screening tool in identifying possible depression in people with stroke both two weeks and three months post stroke.
Circadian Organization oftau Mutant Hamsters: Aftereffects and Splitting
Authors: Bittman Eric L. , Costello Mary K. , McKinley Brewer Judy
Published: September 2007

Homozygous tau mutant (τss) hamsters show an extremely short (20 h) circadian period (τ) that is attributable to altered enzymatic activity of casein kinase 1ε. It has been proposed that coupling of constituent circadian oscillators is strengthened in τss hamsters, explaining their tendency to show strong resetting after prolonged exposure to constant darkness. To evaluate further the circadian organization of τss hamsters, the authors assessed the extent of shortening of period as an aftereffect of exposure to light:dark cycles whose period (T) is 91% of τ and the ability of constant light to induce splitting. They find that τss hamsters show aftereffects comparable to wild types, indicating that normal CK1ε activity is not required for T cycles to shorten τ. This finding also contradicts the proposal that circadian period is homeostatically conserved. However, the authors find that τss hamsters rarely show splitting in constant light. Furthermore, LL does not induce lengthening of τ or reduction of activity duration (α) in these mutants. The authors' findings support the conclusion that the τ mutation alters the coupling between constituent circadian oscillators.
The Retina-Attached SCN Slice Preparation: An In Vitro Mammalian Circadian Visual System
Authors: Wong Kwoon Y. , Graham Dustin M. , Berson David M.
Published: September 2007

The suprachiasmatic nucleus (SCN), the mammalian circadian pacemaker, receives information about ambient light levels through the retinohypothalamic tract. This information resets the molecular clock of SCN neurons, thereby entraining overt animal behavior and physiology to the solar cycle. Progress toward functional characterization of retinal influences on the SCN has been hampered by limitations of established experimental paradigms. To overcome this hurdle, the authors have developed a novel in vitro preparation of the rat retinohypothalamic circuit that maintains functional connectivity between the retinas and the SCN. This method permits whole-cell patch-clamp recordings from visually identified, light-responsive SCN neurons. Using this preparation, the authors have found that in the SCN, light-evoked responses are partly driven by the melanopsin photosensory system of the intrinsically photosensitive retinal ganglion cells and that SCN neurons exhibit light adaptation. The authors have also been able to generate this preparation from mice, demonstrating the feasibility of applying this method to transgenic mice.
Modeling the Electrophysiology of Suprachiasmatic Nucleus Neurons
Authors: Choon Kiat Sim  , Forger Daniel B.
Published: September 2007

Neurons in the SCN act as the central circadian (~24-h) pacemaker in mammals. Using measurements of the ionic currents in SCN neurons, the authors fit a Hodgkin-Huxley-type model that accurately reproduces slow (~2-8 Hz) neural firing as well as the contributions of ionic currents during an action potential. When inputs of other SCN neurons are considered, the model accurately predicts the fractal nature of firing rates and the appearance of random bursting. In agreement with experimental data, the molecular clock within these neurons modulates the firing rate through small changes in the concentration of internal calcium, calcium channels, or potassium channels. Predictions are made on how signals from other neurons can start, stop, speed up, or slow down firing. Only a slow sodium inactivation variable and voltage do not reach equilibrium during the interval between action potentials, and based on this finding, a reduced model is formulated.
Blue intensity in Pinus sylvestris tree-rings: developing a new palaeoclimate proxy
Authors: Campbell Rochelle , McCarroll Danny , Loader Neil J. , Grudd Håkan , Robertson Iain , Jalkanen Risto
Published: September 2007

Minimum blue intensity measurements of resin-extracted Pinus sylvestris (L.) samples, conducted using a flat-bed scanner and commercially available software, are shown to provide a robust and reliable surrogate for maximum latewood density. Blue intensity data from 15 trees, from three stands, are reported relative to a standard blue-scale in a manner similar to grey-scale calibration in x-ray densitometry. The resulting time series are highly correlated with x-ray densitometry data generated from the same samples and preserve the same high level of signal strength. Sensitivity to summer climate variables is similar to that identified in the relative density record, demonstrating that minimum blue intensity can also be used for the study of climate change. While not a replacement for the powerful range of x-ray densitometry techniques, blue intensity provides an inexpensive and accessible alternative for accessing palaeoclimatic information.
Searching for a research agenda for the Library and Information Science community
Authors: Goulding Anne
Published: September 2007

Discusses a workshop focusing on research in the UK LIS (Library and Information Science) sector held at the British Library in November 2006. Outlines the presentations given at the workshop on the history of research in the sector, current developments and the role of practice-led research. Expresses concern about the fragmentation of funding for research into LIS, particularly that for applied, practice-based research. Suggests that leadership is needed to establish a research agenda for the sector and drive it forward.
Multitasking information behaviour in public libraries. A survey study
Authors: Spink Amanda , Alvarado-Albertorio Frances , Narayan Bhuva , Brumfield Jean , Park Minsoo
Published: September 2007

Multitasking information behaviour is the human ability to handle the demands of multiple information tasks concurrently. When we multitask, we work on two or more tasks and switch between those tasks. Multitasking is the way most of us deal with the complex environment we all live in, and recent studies show that people often engage in multitasking information behaviours. Multitasking information behaviours are little understood, however, and an important area of research for information behaviour research. Our study investigated the multitasking information behaviours of public library users at the Brentwood and Wilkinsburg Public Libraries in Pittsburgh through diary questionnaires. Findings include that some 63.5 percent of library users engaged in multitasking information behaviours, with a mean of 2.5 topic changes and 2.8 topics per library visit. A major finding of our study is that many people in libraries are seeking information on multiple topics and are engaged in multitasking behaviours. The implications of our findings and further research are also discussed.
Studying Philology Today
Authors: Castanyer Laura Borràs
Published: September 2007

As higher education is currently undergoing a radical transformation throughout Europe, philological studies face challenges from both inside and outside the discipline, some of which put into question the very existence of the field. This article investigates whether this crisis can also be seen as an opportunity for a profound rethinking of the field, not only necessary for its survival but also more effective with regards to its original goals in the context of a humanistic education. The author sees the advent of digital technologies and new concepts of textuality as a positive development and draws on her experience in virtual teaching at the Universitat Oberta de Catalunya (UOC), seeking for new conceptual frameworks through which the quality of literary teaching and learning in higher education may be improved.
Jesus the Israelite Was Neither a `Jew' Nor a `Christian': On Correcting Misleading Nomenclature
Authors: Elliott John
Published: September 2007

Distinguishing between insider and outsider groups and their differing nomenclatures is essential for accurate interpretation and translation. Jesus and his earliest followers, evidence demonstrates, were called `Israelites', `Galileans' or `Nazoreans' by their fellow Israelites. `Israel', `Israelites' were the preferred terms of self-designation among members of the house of Israel when addressing other members—not `'Ιουδαιος', `Jew' or `Judaism'. Modern interpreters and translators of the Bible, it is argued, should respect and follow this insider preference. 'Ιουδαιος , an outsider coinage, is best rendered `Judaean', not `Jew', to reflect the explicit or implied connection with Judaea. It was employed by Israelites when addressing outsiders as an accommodation to outsider usage. The concepts `Jew', `Jewish' and `Christian' as understood today are shaped more by fourth century rather than first-century CE realities and hence should be avoided as anachronistic designations for first-century persons or groups. Use of `Christian' is best restricted to its three NT appearances. The use of appropriate nomenclature is crucial for minimizing historical and social inaccuracies and misunderstandings.
Did the Historical Jesus Prohibit All Oaths?: Part 1
Authors: Meier John
Published: September 2007

The total prohibition of oaths (Mt. 5.34-37) come from the historical Jesus. The criterion of discontinuity argues that there is no parallel to Jesus' total prohibition of oaths in the Jewish Scriptures, the intertestamental literature prior to 70 CE, or the New Testament. The Jewish Scriptures take oaths for granted and impose them in a few cases. Apart from Jas 5.12, the New Tetsament knows of no prohibition; Paul uses oaths with abandon. The criterion of multiple attestation argues that Jas 5.12 represents an independent tradition of the prohibition; Jas 5.12 is parallel to Mt. 5.34-37 in both content and structure; James has other examples of Jesus' sayings woven into his epistle without attribution; and Jas 5.12 is at odds with James's treatment of the Law in the rest of his epistle. Hence Jas 5.12 qualifies as an independent witness to an isolated stream of oral tradition preserving Jesus' prohibition. This is Part 1 of a two-part essay.
Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity
Authors: Dannull Jens , Lesher Diem-Thu , Holzknecht Robert , Qi Wenning , Hanna Gabi , Seigler Hilliard , Tyler Douglas S. , Pruitt Scott K.
Published: September 2007

The process of dendritic cell (DC) maturation, critical for effective DC-based immunotherapy, also alters the proteasome such that peptides presented in the context of HLA class I are generated not by the constitutive proteasome, but by the immunoproteasome. Cytotoxic T lymphocytes (CTLs) induced by such DCs might not optimally recognize tumor cells normally expressing the constitutive proteasome. Using small interfering RNA (siRNA) transfection of DCs to inhibit expression of the 3 inducible immunoproteasome subunits in mature DCs, we found that such DCs expressed increased intracellular levels of constitutive proteasomes and presented an altered repertoire of tumor-antigenic peptides. When DCs generated from the monocytes of 3 patients with melanoma were transfected with immunoproteasome siRNA, induced to mature, and then trans-fected with RNA encoding defined melanoma antigens, these DCs were superior inducers of antigen-specific CTLs against autologous melanoma cells. This alteration of DC proteasome composition, which enhances the ability of mature antigen-loaded DCs to stimulate anti-tumor immune responses, may lead to more effective DC-based tumor immunotherapy.
Hepatitis C virus infection and risk of posttransplantation lymphoproliferative disorder among solid organ transplant recipients
Authors: Morton Lindsay M. , Landgren Ola , Chatterjee Nilanjan , Castenson David , Parsons Ruth , Hoover Robert N. , Engels Eric A.
Published: September 2007

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Hepatitis C virus (HCV) infection has been linked to increased risk of lymphoma among immunocompetent individuals. We therefore investigated the association between HCV infection and PTLD in a retrospective cohort study of all individuals in the United States who received their first solid organ transplant from 1994 to 2005 (N = 210 763) using Scientific Registry of Transplant Recipients data. During follow-up, 1630 patients with PTLD were diagnosed. HCV prevalence at transplantation was 11.3%. HCV infection did not increase PTLD risk in the total cohort (Cox regression model, hazard ratio [HR] = 0.84; 95% confidence interval [CI] 0.68-1.05), even after adjustment for type of organ transplanted, indication for transplantation, degree of HLA mismatch, donor type, or use of immunosuppression medications. Additional analyses also revealed no association by PTLD subtype (defined by site, pathology, cell type, and tumor Epstein-Barr virus [EBV] status). HCV infection did increase PTLD risk among the 2.8% of patients (N = 5959) who were not reported to have received immunosuppression maintenance medications prior to hospital discharge (HR = 3.09; 95% CI, 1.14-8.42; P interaction = .007). Our findings suggest that HCV is not a major risk factor for PTLD, which is consistent with the model in which an intact immune system is necessary for development of HCV-related lymphoproliferation.
Molecular evolution of type VI intermediate filament proteins
Authors: Guérette Dominique , Khan Paul A , Savard Pierre E , Vincent Michel
Published: September 2007

Background

Tanabin, transitin and nestin are type VI intermediate filament (IF) proteins that are developmentally regulated in frogs, birds and mammals, respectively. Tanabin is expressed in the growth cones of embryonic vertebrate neurons, whereas transitin and nestin are found in myogenic and neurogenic cells. Another type VI IF protein, synemin, is expressed in undifferentiated and mature muscle cells of birds and mammals. In addition to an IF-typical α-helical core domain, type VI IF proteins are characterized by a long C-terminal tail often containing distinct repeated motifs. The molecular evolution of type VI IF proteins remains poorly studied.

Results

To examine the evolutionary history of type VI IF proteins, sequence comparisons, BLAST searches, synteny studies and phylogenic analyses were performed. This study provides new evidence that tanabin, transitin and nestin are indeed orthologous type VI IF proteins. It demonstrates that tanabin, transitin and nestin genes share intron positions and sequence identities, have a similar chromosomal context and display closely related positions in phylogenic analyses. Despite this homology, fast evolution rates of their C-terminal extremity have caused the appearance of repeated motifs with distinct biological activities. In particular, our in silico and in vitro analyses of their tail domain have shown that (avian) transitin, but not (mammalian) nestin, contains a repeat domain displaying nucleotide hydrolysis activity.

Conclusion

These analyses of the evolutionary history of the IF proteins fit with a model in which type VI IFs form a branch distinct from NF proteins and are composed of two major proteins: synemin and nestin orthologs. Rapid evolution of the C-terminal extremity of nestin orthologs could be responsible for their divergent functions.
A Marfan syndrome gene expression phenotype in cultured skin fibroblasts
Authors: Yao Zizhen , Jaeger Jochen C , Ruzzo Walter L , Morale Cecile Z , Emond Mary , Francke Uta , Milewicz Dianna M , Schwartz Stephen M , Mulvihill Eileen R
Published: September 2007

Background

Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms.

Results

We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR.

Conclusion

Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value < 3 × 10-6 under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status). An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater.
Passage and reversal effects on gene expression of bovine meniscal fibrochondrocytes
Authors: Gunja Najmuddin J , Athanasiou Kyriacos A
Published: September 2007

The knee meniscus contains a mixed population of cells that exhibit fibroblastic as well as chondrocytic characteristics. Tissue engineering studies and future therapies for the meniscus require a large population of cells that are seeded on scaffolds. To achieve this, monolayer expansion is often used as a technique to increase cell number. However, the phenotype of these cells may be significantly different from that of the primary population. The objective of this study was to investigate changes in meniscal fibrochondrocytes at the gene expression level over four passages using quantitative real-time reverse transcriptase polymerase chain reaction. Cells from the inner two-thirds of bovine medial menisci were used. Four extracellular matrix (ECM) molecules, commonly found in the meniscus, were investigated, namely collagen I, collagen II, aggrecan and cartilage oligomeric matrix protein (COMP). In addition, primary and passaged meniscus fibrochondrocytes were placed on surfaces coated with collagen I or aggrecan protein to investigate whether any gene expression changes resulting from passage could be reversed. Collagen I expression was found to increase with the number of passages, whereas collagen II and COMP expression decreased. Collagen I and aggrecan surface coatings were shown to downregulate and upregulate collagen I and COMP expression levels, respectively, in passaged cells. However, decreases in collagen II expression could not be reversed by either protein coating. These results indicate that although monolayer expansion results in significant changes in gene expression in meniscal fibrochondrocytes, protein coatings may be used to regain the primary cell expression of several ECM molecules.
BP1 transcriptionally activates bcl-2and inhibits TNFα-induced cell death in MCF7 breast cancer cells
Authors: Stevenson Holly S , Fu Sidney W , Pinzone Joseph J , Rheey Jinguen , Simmens Samuel J , Berg Patricia E
Published: September 2007

Introduction

We have previously shown that the Beta Protein 1 (BP1) homeodomain protein is expressed in 81% of invasive ductal breast carcinomas, and that increased BP1 expression correlates with tumor progression. The purpose of our current investigation was to determine whether elevated levels of BP1 in breast cancer cells are associated with increased cell survival.

Methods

Effects on cell viability and apoptosis of MCF7 cells stably overexpressing BP1 were determined using MTT and Annexin V assays, and through examination of caspase activation. TNFα was used to induce apoptosis. The potential regulation of apoptosis-associated genes by BP1 was studied using real-time PCR and western blot analyses. Electrophoretic mobility shift assays, site-directed mutagenesis, and transient assays were performed to specifically characterize the interaction of BP1 with the promoter of the bcl-2 gene.

Results

Stable overexpression of BP1 led to inhibition of apoptosis in MCF7 breast cancer cells challenged with TNFα. Increased BP1 resulted in reduced processing and activation of caspase-7, caspase-8, and caspase-9, and inactivation of the caspase substrate Poly(ADP-Ribose) Polymerase (PARP). Increased levels of full-length PARP and a decrease in procaspase-8 were also associated with BP1 overexpression. The bcl-2 gene is a direct target of BP1 since: (i) BP1 protein bound to a consensus binding sequence upstream of the bcl-2 P1 promoter in vitro. (ii) MCF7 cells overexpressing BP1 showed increased levels of bcl-2 mRNA and protein. (iii) Transient assays indicated that increased bcl-2 promoter activity is due to direct binding and modulation by BP1 protein. BP1 expression also prevented TNFα-mediated downregulation of bcl-2 mRNA and protein.

Conclusion

These findings suggest mechanisms by which increased BP1 may impart a survival advantage to breast cancer cells, which could lead to increased resistance to therapeutic agents in patients.
Pharmacokinetics and pharmacodynamics of danaparoid during continuous venovenous hemofiltration: a pilot study
Authors: de Pont Anne-Cornélie JM , Hofstra Jorrit-Jan H , Pik Derk R , Meijers Joost CM , Schultz Marcus J
Published: September 2007

Background

In patients with suspected heparin-induced thrombocytopenia (HIT) who need renal replacement therapy, a nonheparin anticoagulant has to be chosen to prevent thrombosis in the extracorporeal circuit. Danaparoid, a low-molecular-weight heparinoid consisting of heparan sulphate, dermatan sulphate, and chondroitin sulphate, is recommended for systemic anticoagulation in patients with HIT. However, there are few data on the use of danaparoid in patients with acute renal failure, especially in patients dependent on renal replacement therapy such as continuous venovenous hemofiltration (CVVH). In the present study, we analyzed the pharmacokinetics and pharmacodynamics of danaparoid during CVVH in patients with suspected HIT.

Methods

Based on a mathematical model, a dosing scheme for danaparoid was designed, aiming at anti-Xa levels of 0.5 to 0.7 U/mL, with a maximum of 1.0 U/mL. This dosing scheme was prospectively tested in the first CVVH run of a cohort of five patients with suspected HIT. CVVH with a blood flow rate of 150 mL/minute and a substitution rate of 2,000 mL/hour was performed with a cellulose triacetate membrane. Danaparoid was administered as a continuous infusion of 100 anti-Xa-U/hour after a loading dose of 3,500 anti-Xa-U. Serial measurements of anti-Xa activity and prothrombin fragment F1+2 were performed at baseline, at t = 5, 15, and 30 minutes, and at t = 1, 2, 4, 8, 16, and 24 hours after the danaparoid loading dose.

Results

The median anti-Xa activity reached a maximum of 1.02 (0.66 to 1.31) anti-Xa-U/mL after 15 minutes and gradually declined to 0.40 (0.15 to 0.58) anti-Xa-U/mL over the span of 24 hours. Target anti-Xa levels were reached from 2 to 12 hours after the loading dose. Median prothrombin fragment F1+2 gradually decreased from 432 (200 to 768) to 262 (248 to 317) pmol/L after 24 hours. No bleeding or thromboembolic events occurred throughout the described treatment period.

Conclusion

Danaparoid administered by a continuous infusion of 100 anti-Xa-U/hour after a loading dose of 3,500 anti-Xa-U elicited target anti-Xa levels from 2 to 12 hours after the loading dose, without bleeding or thromboembolic events during the described CVVH treatment in patients with suspected HIT.
Social regulation of gene expression in human leukocytes
Authors: Cole Steve W , Hawkley Louise C , Arevalo Jesusa M , Sung Caroline Y , Rose Robert M , Cacioppo John T
Published: September 2007

Background

Social environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates.

Results

DNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low-lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements (GREs; p = 0.032) and over-expression of genes bearing response elements for pro-inflammatory NF-κB/Rel transcription factors (p = 0.011). This reciprocal shift in pro- and anti-inflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB/ATF, JAK/STAT, IRF1, C/EBP, Oct, and GATA pathways.

Conclusion

These data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation.
A Bridge Between Academic and Community Radiation Oncology Treatment Planning
Authors: Maguire Patrick D. , Honaker Geoff , Neal Charles , Meyerson Martin , Morris David , Rosenman Julian , Tepper Joel
Published: September 2007

Purpose

To evaluate Telesynergy (TS) as a method of interactive treatment planning between academic and community radiation oncology departments.

Methods

Through a grant from the National Cancer Institute to improve cancer outcomes for underserved populations, community radiation oncologists at New Hanover Regional Medical Center (NHRMC) in Wilmington, North Carolina, partnered with those at the University of North Carolina (UNC) in Chapel Hill, North Carolina. TS suites were installed at both sites to facilitate teleconferencing and review of treatment planning for intensity-modulated radiation therapy (IMRT). Patients with locally advanced head and neck cancer at NHRMC who were enrolled on a clinical trial of chemoirradiation underwent IMRT planning utilizing commercial software. NHRMC physicians contoured tumor targets and adjacent healthy organs. Physics staff at NHRMC generated an initial IMRT plan for each patient. Radiation oncologists at UNC then reviewed individual IMRT plans via TS conferences.

Results and Conclusion

Between August 2004 and August 2005, seven IMRT plans were reviewed in eight TS conferences. Physician contours of tumor targets and healthy organs, dose volume histograms, IMRT beams, and isodose distributions were shared during each TS conference successfully. Median time for each session was 35 minutes (range, 30 to 75). Physician satisfaction with the interactive planning process was high at both NHRMC and UNC. A cycle would likely evolve of initial intensive use of TS conferences, to gradual use for ongoing quality control, then greater use as the treatment planning technology undergoes its next change. Complex IMRT treatment planning review was feasible between an academic and community hospital via TS with a high level of physician participant satisfaction.
Litigating the Science of Breast Cancer Treatment
Authors: Jacobson Peter D. , Rettig Richard A. , Aubry Wade M.
Published: September 2007

Beginning in the late 1980s, many health insurers refused to cover high-dose chemotherapy with autologous bone marrow transplant (HDC/ABMT) for high-risk and metastatic breast cancer patients. Insurers denied coverage because there was no persuasive evidence of clinical effectiveness. In response, many women sued to compel coverage. After years of litigation and the expenditure of approximately $3 billion, randomized clinical trials (RCTs) showed that the procedure was no more effective and possibly more harmful than conventional therapy.

To understand whether and how litigation contributed to the diffusion of the procedure, we conducted a series of case studies that examine the litigation tactics and strategies used by defense and plaintiffs' counsel. Despite the fact that HDC/ABMT lacked proven scientific effectiveness, insurance defense attorneys were unable to stop the procedure's diffusion. Plaintiffs' attorneys had a much easier and more sympathetic story to tell and were able to exploit vulnerabilities facing the defense.
Medical Malpractice Reform and Insurer Claims Defense: Unintended Effects?
Authors: Ambrose Jan M. , Carroll Anne
Published: September 2007

In response to recent and past medical malpractice insurance crises, most states have implemented reforms meant to stabilize premiums and coverage availability. The importance of understanding whether these reforms implicitly affect the behavior and incentives of plaintiffs, attorneys, medical providers, and malpractice insurers in the intended way is crucial to policy makers, if they are to achieve their goal. This study specifically examines the effect of reforms on the claims defense efforts of insurers, given that defense expenses account for approximately 30 percent of malpractice premiums. Using state data for the period 1998-2002, we regress claims defense expenses against a variety of reform variables. These include seven tort reforms (noneconomic damage caps, punitive damage limits, attorney fee limits, modified collateral source rule, modified joint and several liability doctrine, mandatory pretrial screening, and statute of limitations) and two government-sponsored insurance mechanisms (joint underwriting associations and patient compensation funds). Claims defense expenses are found to be higher in the presence of noneconomic damage caps, punitive damage limits, and attorney fee limits—an unintended and counterproductive effect of reform—but are lower with mandatory pretrial screening and patient compensation funds.
Velocity and turbulence measurements in a separating boundary layer with and without passive flow control
Authors: Satta F , Simoni D , Ubaldi M , Zunino P , Bertini F , Spano E
Published: September 2007

The present paper reports the results of a detailed experimental study on low profile vortex generators (VGs) used to control boundary layer separation on a large-scale flat plate with prescribed adverse pressure gradients. This activity is part of a joint European research program on Aggressive Intermediate Duct Aerodynamics.

The inlet turbulent boundary layer and the pressure gradient over the flat plate are representative of aggressive turbine intermediate ducts. By regulating the inclination of the wall opposite to the flat plate, different pressure gradients, typical of turbine intermediate ducts, can be obtained. To avoid separation on the movable wall, boundary layer suction is applied.

Previous measurements showed the effectiveness of VGs in delaying separation and revealed their optimum configuration for the different prescribed pressure gradients. In the present work, laser Doppler velocimetry (LDV) is applied to the most significant pressure gradient case, in order to obtain a more thorough knowledge of the near-wall flow field. Velocity and turbulence profiles are determined up to the near-wall region in order to provide an in-depth analysis of turbulent boundary layer at separation conditions, with and without application of control devices. LDV allowed high spatial resolution and accurate statistical analysis of the boundary layer velocities.

The results show velocity and turbulence profiles typical of separated turbulent boundary layers for the baseline case, and non-conventional unseparated boundary layer profiles when VGs are installed on the flat plate.
Accounting for losses and definitions of efficiency in turbomachinery stages
Authors: Casey M. V.
Published: September 2007

A method of accounting for losses and defining efficiencies in the blade rows of adiabatic turbomachinery stages is described. This is based on the concept of specific dissipation work which is the integral of the product of local temperature and entropy change due to the losses (∫ T d s). This formulation allows various entropy-based efficiencies and loss coefficients to be derived with equations that are exact for all types of fluid (liquids, ideal gases, and real gases). The expressions for the polytropic and isothermal efficiency, as well as for the Markov blade row loss coefficient, resulting from this can be directly visualized in a Mollier chart ( h-s diagram) as the ratio of entropy and enthalpy changes between two real states and a single virtual state.
Analysis of the shroud leakage flow and mainflow interactions in high-pressure turbines using an unsteady computational fluid dynamics approach
Authors: Adami P , Martelli F , Cecchi S
Published: September 2007

Endwall leakage flows interaction in shrouded high-pressure steam turbines is investigated to provide insights about loss and performances. The prediction of flow through the seal and the understanding of the leakage jet interaction with the main flow is performed using computational fluid dynamics (CFD). A modern research solver is used coupling the labyrinth and the main vane flows including most of the relevant geometric and aerodynamic features. Two similar shroud configurations are here analysed for two high-pressure turbine configurations. Each configuration refers to a different blade technology commonly used by Ansaldo Energia. The computational algorithm is based on a numerical solver developed and applied to solve the compressible Navier-Stokes equations in a multi-rows unsteady environment. The problem has been approached modelling the unsteady 1.5-stage interaction. The CFD results are commented addressing the potential source of losses.
Performance analysis of a transonic high-pressure turbine
Authors: Yasa T , Paniagua G , Bussolin A
Published: September 2007

Efficiency is a crucial design parameter in any turbine development. This research presents a detailed investigation on the efficiency of a modern transonic high-pressure turbine. The work focuses on the study of the efficiency loss at different stage loading factors (ranging from Δ H/U2 = 1.3 to 2.7) and various flow factors ( Vax/ U = 0.41 to 0.90). In particular, the present research is of utmost importance to understand the effect of the vane trailing edge shocks in the turbine stage efficiency.

The experimental work was carried out in a compression tube facility that allows testing of the turbine at temperature ratios, Re and Mach numbers, encountered in real engines. The efficiency is measured by the mechanical method. Experiments were performed with two different vanes (cooled and uncooled) at two stagger angles, four rotational speeds (4570–6500 r/min) and three pressure ratios ( p01/ Ps3 ranging from 2.42 to 5.12). The effect of the change of reaction and rotor incidence is correlated with the performance. Three-dimensional Navier-Stokes calculations aid the interpretation of the results.
Stereoselective Conjugate Addition Reactions Using In Situ Metallated Terminal Alkynes and the Development of Novel Chiral P,N-Ligands
Authors: Fujimori Shinji , Knöpfel Thomas F , Zarotti Pablo , Ichikawa Takashi , Boyall Dean , Carreira Erick M
Published: September 2007

In this account, new methods for the catalytic and stereoselective conjugate addition of terminal alkynes are described. Our laboratories have disclosed asymmetric addition reactions to aldehydes and imines using a combination of a zinc or copper salt and a terminal alkyne. Under these conditions, terminal alkyne is transformed in situ into an alkynyl metal species. Recently, it was found that these in situ generated alkynyl metal species can undergo conjugate additions to alkylidene malonate-type acceptors. In the zinc(II) triflate-catalyzed system, a highly diastereoselective conjugate addition has been realized using a chiral oxazepene acceptor. Subsequently, alternative conjugate addition protocols have been developed which employ a terminal alkyne, substoichiometric amounts of copper and a highly eletrophilic Meldrum’s acid derived acceptor. This reaction can be made enantioselective using a novel atropisomeric P,N-ligand (PINAP). With this ligand, excellent enantioselectivities can be achieved for the conjugate addition of aromatic alkynes to various Meldrum’s acid derived acceptors.
Total Synthesis of Epoxyquinonoid Natural Products
Authors: Shoji Mitsuru
Published: September 2007

Asymmetric total synthesis of epoxyquinonoid natural products, such as epoxyquinols A, B, and C, epoxytwinol A, and EI-1941-1, -2, and -3, are described. In the first-generation synthesis of epoxyquinols, the HfCl4-mediated diastereoselective Diels–Alder reaction of furan with a chiral acrylate ester was developed. In the second-generation synthesis, a chromatography-free preparation of an iodolactone by using acryloyl chloride as the dienophile in the Diels–Alder reaction of furan, and the lipase-mediated kinetic resolution of a cyclohexenol derivative were developed. This second-generation synthesis is suitable for large-scale preparation. A biomimetic cascade reaction involving oxidation, 6π-electrocyclization, then Diels–Alder dimerization, is the key reaction in the formation of epoxyquinols A–C. Epoxytwinol A was synthesized by the cascade reaction composed of oxidation, 6π-electrocyclization, and formal [4+4] cycloaddition. A 2H-pyran, generated by oxidation/6π-electrocyclization, acts as a good diene, reacting with several dienophiles to afford polycyclic compounds in one step. The asymmetric total synthesis of EI-1941s was accomplished, starting from a chiral epoxy iodoquinone, a key intermediate in the total synthesis of epoxyquinols. They were diastereoselectively synthesized via an intramolecular carboxypalladation in a 6-endo cyclization mode, followed by β-hydride elimination, as the key steps.
The Self-Assembly of Amphiphilic Oligothiophenes: Hydrogen Bonding and Poly(glutamate) Complexation
Authors: Brustolin Fiorella , Surin Mathieu , Lemaur Vincent , Romanazzi Giuseppe , Sun Qianyao , Cornil Jérôme , Lazzaroni Roberto , Sommerdijk Nico A J M , Leclère Philippe , Meijer E W
Published: September 2007

The self-organization behavior of an amphiphilic sexithiophene bearing amide functionalities is studied and compared to that of a derivative bearing an ester group at the same position. The introduction of hydrogen-bond interactions in assemblies of these π-conjugated oligomers is found to affect the molecular organization both in protic media and in thin deposits on mica. The amphiphilic 2,2′;5′,2'';5'',2''';5''',2'''';5'''',2'''''-sexithiophene-5,5'''''-dicarboxylic acid bis[(4,7,10,13,16-pentaoxaheptadecyl)amide] forms assemblies in n-butanol and water and partially aggregates in toluene. Spectroscopy reveals that the presence of a hydrogen-bonding moiety increases the thermal stability of the assemblies in n-butanol and even more in water solution. On mica surfaces, the formation of rod-like one-dimensional nanostructures is observed after deposition from toluene solutions. In addition, transmission electron microscopy in combination with selected area electron diffraction shows that in water plate-like structures are formed built from parallel oriented stacks, with a π–π distance of 3.5 Å. Comparison of these data to molecular modeling and quantum chemistry calculations is used to better understand the influence of the amide group on the stacking of these compounds. The introduction of these H-bonding interactions leads to denser and more stable stacks. Furthermore, we show that a derivative of the amide compound, bearing terminal ammonium groups, forms a complex with chiral polyanions in aqueous media such that the sexithiophene segments are stacked in a meta-stable helical fashion with preferred handedness. We observed that poly(glutamate) and DNA generate a chiral sexithiophene assembly. In time the induced chirality disappears, which is explained by the meta-stability of the kinetically formed adduct. This constitutes one step forward towards the controlled formation of functional multi-component systems in aqueous solution.
Change in the Orientation and Packing upon Adsorption of Pyranine Molecules onto Cationic Langmuir Monolayers and Langmuir–Blodgett Films
Authors: Tsukamoto Osamu , Villeneuve Masumi , Sakamoto Akira , Nakahara Hiroo
Published: September 2007

Differrent adsorption behaviors and the orientation of pyranine molecules were investigated for the cationic Langmuir monolayers by using Brewster angle microscopy (BAM), two-dimensional (2D) phase behavior with elasticitic property of the monolayers and in situ visible spectroscopy. The structural change in the cationic Langmuir–Blodgett (LB) films before and after adsorbing pyranine molecules was found by using small angle and in-plane XRD. The excited-state proton-transfer (ESPT) between octadecylamine (ODA) and pyranine adsorbed in the films was investigated using time-resolved fluorescence spectroscopy together with consideration of the film structures.
Spectroelectrochemical Study of the Reversible Adduct Formation of Bis(phthalocyaninato)neodymate(III) Complex with CO2 in a DMF Solution
Authors: Wulan Qiqige , Kitamura Fusao
Published: September 2007

The reaction between CO2 and electrochemically reduced bis(phthalocyaninato)neodymate(III) complex in a dimethylformamide solution was investigated by cyclic voltammetry and in situ visible spectroscopy. The introduction of gaseous CO2 into the phthalocyanine solution caused a considerable increase in the first reduction peak current of the complex and a shift in the second reduction peak to more positive potentials. In addition, new anodic current peaks appeared in the reverse sweep at potentials different from those of the complex. These observations were explained in terms of the formation of a CO2-adduct. The formation and decomposition of the CO2-adducts occurred reversibly with the applied potential, which was confirmed by in situ visible spectroscopy.
Through-Space Interactions in Non-Kekulé Biradicals
Authors: Hatanaka Masashi , Shiba Ryuichi
Published: September 2007

Through-space interactions in non-Kekulé biradicals were analyzed. We defined PNBMOi,j as a product of i-th and j-th NBMO of non-Kekulé biradicals. Whereas through-space interactions between non-nearest-neighbor carbon atomic sites in PNBMOi,j were negligible in so-called disjoint-type biradicals, antibonding-through-space interactions between second-nearest-neighbor carbon atomic sites in PNBMOi,j destabilized the singlet states in so-called nondisjoint-type biradicals. The instabilities in the singlet states contributed to the triplet state preference for nondisjoint-type biradicals.